Publications of Bastiaan Driehuys    :recent first  alphabetical  combined listing:

%% Papers Published   
@article{fds171982,
   Title = {SELECTED PEER-REVIEWED PUBLICATIONS:

1. B Driehuys, GP Cofer, J Pollaro, et al., Imaging alveolar-capillary gas transfer using hyperpolarized 129Xe MRI, Proceedings of the National Academy of Sciences, 103(48): 18278-18283, 2006.
2. JP Mugler, B Driehuys, JR Brookeman et al., MR imaging and spectroscopy using hyperpolarized 129Xe gas: Preliminary human results, Magn. Reson. Med. 37, 809-815, 1997.
3. Driehuys B, Moller HE, Cleveland ZI, Pollaro J, Hedlund LW. Pulmonary perfusion and xenon gas exchange in rats: MR imaging with intravenous injection of hyperpolarized Xe-129. Radiology 252(2):386-393, 2009.
4. S. Mansson, J Wolber, B Driehuys et al., Characterization of diffusing capacity and perfusion of the rat lung in a lipopolysaccaride disease model using hyperpolarized 129Xe, Magn. Reson. Med. 50 (6), 1170-1179, 2003.
5. B Driehuys, GD Cates, E Miron et al., High-volume production of laser-polarized 129Xe, Appl. Phys. Lett. 69 (12), 1668-1670, 1996.

Most Recent:

1. B Driehuys, J Pollaro, GP Cofer. In vivo MRI using real-time production of hyperpolarized Xe-129. Magn. Reson. Med. 60:14-20, 2008. PMCID2548276
2. AC Thomas, EN Potts, BT Chen, DM Slipetz, WM Foster, B Driehuys. A robust protocol for regional evaluation of methacholine challenge in mouse models of allergic asthma using hyperpolarized He-3 MRI. NMR Biomed. 22(5):502-515, 2009. PMCID114021
3. Cleveland ZI, Moeller HE, Hedlund L, Driehuys B. Continuously infusing hyperpolarized 129xe into flowing aqueous solutions using hydrophobic gas exchange membranes. Journal of Physical Chemistry B 2009;113(37):12489-12499. PMCID2747043
4. Branca T, Cleveland ZI, Leuschner C, Kumar C, Fubara B, Maronpot RR, Warren W, Driehuys B. Hyperpolarized 3He MRI to detect lung metastases targeted by magnetic nanoparticles. Proc. Natl. Acad. Sci. in press.
5. Mistry N, Thomas A, Kaushik SS, Driehuys B. Quantitative analysis of hyperpolarized 3He ventilation changes in mice challenged with methacholine, Magn Reson Med, in press.

Best:
1. MS Albert, GD Cates, B Driehuys et al., Biological magnetic-resonance imaging using laser polarized 129Xe, Nature 370 (6486), 199-201, 1994.
2. B Driehuys, J Nouls, A Badea, et al., Small-animal imaging with magnetic resonance microscopy, invited paper, ILAR journal, 28(1): 35-53, 2008.
3. B Driehuys, J Walker, J Pollaro, et al., Hyperpolarized 3He MR imaging of methacholine challenge in a mouse model of asthma, Magn. Reson. Med., 58(5), 893-900, 2007. PMC2746053
4. JR MacFall, HC Charles, RD Black, B Driehuys et al., Human lung air spaces: Potential for MR imaging with hyperpolarized He-3, Radiology 200 (2), 553-558, 1996.
5. XJ Chen, HE Moller, MS Chawla, B Driehuys, et al, Spatially resolved measurements of hyperpolarized gas properties in the lung in vivo: Diffusion coefficient, Magn. Reson. Med. 42 (4), 721-728, 1999.

}, Key = {fds171982} } @article{fds268629, Author = {KAMPWIRTH, RT and GRACE, JM and MILLER, DJ and MCDONALD, DB and GRAY, KE and ANDERSEN, PH and DRIEHUYS, B and REITEN, M and ASCOLESE, M}, Title = {INSITU GROWTH OF SUPERCONDUCTING FILMS OF BI SR CA CU O USING MAGNETRON SPUTTERING}, Journal = {SCIENCE AND TECHNOLOGY OF THIN FILM SUPERCONDUCTORS 2}, Pages = {39-46}, Year = {1990}, ISBN = {0-306-43803-8}, url = {http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:A1990BT68M00005&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=47d3190e77e5a3a53558812f597b0b92}, Key = {fds268629} } @article{fds268634, Author = {MILLER, DJ and GRACE, JM and MCDONALD, DB and GRAY, KE and KAMPWIRTH, RT and DRIEHUYS, B}, Title = {MICROSTRUCTURE OF SPUTTERED SUPERCONDUCTING FILMS OF BI2SR2CACU2OX MADE BY LOW-TEMPERATURE, INSITU GROWTH}, Journal = {HIGH TEMPERATURE SUPERCONDUCTING COMPOUNDS II}, Pages = {329-339}, Year = {1990}, ISBN = {0-87339-153-5}, url = {http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:A1990BS29Q00025&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=47d3190e77e5a3a53558812f597b0b92}, Key = {fds268634} } @article{fds268641, Author = {Driehuys, B and Cates, GD and Happer, W and Mabuchi, H and Saam, B and Albert, MS and Wishnia, A}, Title = {Spin transfer between laser-polarized 129Xe nuclei and surface protons}, Journal = {Physics Letters A}, Volume = {184}, Number = {1}, Pages = {88-92}, Year = {1993}, ISSN = {0375-9601}, Abstract = {We have demonstrated a large polarization transfer from highly polarized gaseous 129Xe to protons in a silicone surface coating. The proton polarization enhancement of ∼ 104-105 over the thermal equilibrium polarization at 0.2 T makes possible the detection of the previously unobservable resonance. We expect that this technique may allow high-resolution NMR to become a viable tool in the study of surfaces. © 1993.}, Key = {fds268641} } @article{fds268678, Author = {Gatzke, M and Cates, GD and Driehuys, B and Fox, D and Happer, W and Saam, B}, Title = {Extraordinarily slow nuclear spin relaxation in frozen laser-polarized 129Xe.}, Journal = {Physical Review Letters}, Volume = {70}, Number = {5}, Pages = {690-693}, Year = {1993}, Month = {February}, ISSN = {1079-7114}, url = {http://www.ncbi.nlm.nih.gov/pubmed/10054178}, Language = {ENG}, Doi = {10.1103/PhysRevLett.70.690}, Key = {fds268678} } @article{fds268688, Author = {Barton, AS and Newbury, NR and Cates, GD and Driehuys, B and Middleton, H and Saam, B}, Title = {Self-calibrating measurement of polarization-dependent frequency shifts from Rb-3He collisions.}, Journal = {Physical Review A - Atomic, Molecular, and Optical Physics}, Volume = {49}, Number = {4}, Pages = {2766-2770}, Year = {1994}, Month = {April}, ISSN = {1050-2947}, url = {http://www.ncbi.nlm.nih.gov/pubmed/9910557}, Language = {ENG}, Key = {fds268688} } @article{fds268665, Author = {Albert, MS and Cates, GD and Driehuys, B and Happer, W and Saam, B and Springer, CS and Wishnia, A}, Title = {Biological magnetic resonance imaging using laser-polarized 129Xe.}, Journal = {Nature}, Volume = {370}, Number = {6486}, Pages = {199-201}, Year = {1994}, Month = {July}, ISSN = {0028-0836}, url = {http://www.ncbi.nlm.nih.gov/pubmed/8028666}, Keywords = {Animals • Lasers • Lung • Magnetic Resonance Imaging • Mice • Water • Xenon Isotopes* • anatomy & histology • methods*}, Abstract = {As currently implemented, magnetic resonance imaging (MRI) relies on the protons of water molecules in tissue to provide the NMR signal. Protons are, however, notoriously difficult to image in some biological environments of interest, notably the lungs and lipid bilayer membranes such as those in the brain. Here we show that 129Xe gas can be used for high-resolution MRI when the nuclear-spin polarization of the atoms is increased by laser optical pumping and spin exchange. This process produces hyperpolarized 129Xe, in which the magnetization is enhanced by a factor of about 10(5). By introducing hyperpolarized 129Xe into mouse lungs we have obtained images of the lung gas space with a speed and a resolution better than those available from proton MRI or emission tomography. As xenon (a safe general anaesthetic) is rapidly and safely transferred from the lungs to blood and thence to other tissues, where it is concentrated in lipid and protein components, images of the circulatory system, the brain and other vital organs can also be obtained. Because the magnetic behaviour of 129Xe is very sensitive to its environment, and is different from that of 1H2O, MRI using hyperpolarized 129Xe should involve distinct and sensitive mechanisms for tissue contrast.}, Language = {eng}, Doi = {10.1038/370199a0}, Key = {fds268665} } @article{fds268642, Author = {Johnson, JR and Thompson, AK and Chupp, TE and Smith, TB and Cates, GD and Driehuys, B and Middleton, H and Newbury, NR and Hughes, EW and Meyer, W}, Title = {The SLAC high-density gaseous polarized 3He target}, Journal = {Nuclear Instruments and Methods in Physics Research Section A: Accelerators, Spectrometers, Detectors and Associated Equipment}, Volume = {356}, Number = {1}, Pages = {148-152}, Year = {1995}, ISSN = {0168-9002}, Abstract = {A large-scale high-pressure gaseous 3He polarized target has been developed for use with a high-intensity polarized electron beam at the Stanford Linear Accelerator Center. This target was used successfully in an experiment to study the spin structure of the neutron. The target provided an areal density of about 7 × 1021 nuclei/cm2 and operated at 3He polarizations between about 30% and 40% for the six-week duration of the experiment. © 1995.}, Key = {fds268642} } @article{fds268670, Author = {Driehuys, B and Cates, GD and Happer, W}, Title = {Surface relaxation mechanisms of laser-polarized 129Xe.}, Journal = {Physical Review Letters}, Volume = {74}, Number = {24}, Pages = {4943-4946}, Year = {1995}, Month = {June}, ISSN = {1079-7114}, url = {http://www.ncbi.nlm.nih.gov/pubmed/10058638}, Language = {ENG}, Doi = {10.1103/PhysRevLett.74.4943}, Key = {fds268670} } @article{fds268643, Author = {Driehuys, B and Cates, GD and Miron, E and Sauer, K and Walter, DK and Happer, W}, Title = {High-volume production of laser-polarized 129Xe}, Journal = {Applied Physics Letters}, Volume = {69}, Number = {12}, Pages = {1668-1670}, Year = {1996}, Abstract = {A method is described for producing several liters of nuclear spin polarized 129Xe gas via spin exchange with an optically pumped Rb vapor. We use a 140 W AlGaAs laser diode array whose broad spectral output is efficiently absorbed by employing ∼ 10 atm of 4He to pressure broaden the Rb D1 absorption profile. 129Xe is polarized in a continuous gas flow and is then cryogenically accumulated and stored. Extensions of this technique should enable the production of tens of liters of 129Xe with a nuclear spin polarization of order 50%. Production of laser-polarized 129Xe in liter quantities is important for the continued development of magnetic resonance imaging using spin-polarized 129Xe. © 1996 American Institute of Physics.}, Key = {fds268643} } @article{fds268662, Author = {Black, RD and Middleton, HL and Cates, GD and Cofer, GP and Driehuys, B and Happer, W and Hedlund, LW and Johnson, GA and Shattuck, MD and Swartz, JC}, Title = {In vivo He-3 MR images of guinea pig lungs.}, Journal = {Radiology}, Volume = {199}, Number = {3}, Pages = {867-870}, Year = {1996}, Month = {June}, ISSN = {0033-8419}, url = {http://www.ncbi.nlm.nih.gov/pubmed/8638019}, Keywords = {Animals • Guinea Pigs • Helium • Lung • Magnetic Resonance Imaging • Male • Radioisotopes • anatomy & histology* • instrumentation • methods* • statistics & numerical data}, Abstract = {The authors imaged the lungs of live guinea pigs with hyperpolarized (HP) helium-3 as a magnetic resonance (MR) signal source. HP He-3 gas produced through spin exchange with rubidium metal vapor was delivered through an MR-compatible, small-animal ventilator. Two- and three-dimensional lung images acquired with ventilation-gated, radial k-space sampling showed complete ventilation of both lungs. All images were of high quality, demonstrating that HP He-3 allows high-signal-intensity MR imaging in living systems.}, Language = {eng}, Doi = {10.1148/radiology.199.3.8638019}, Key = {fds268662} } @article{fds268677, Author = {MacFall, JR and Charles, HC and Black, RD and Middleton, H and Swartz, JC and Saam, B and Driehuys, B and Erickson, C and Happer, W and Cates, GD and Johnson, GA and Ravin, CE}, Title = {Human lung air spaces: potential for MR imaging with hyperpolarized He-3.}, Journal = {Radiology}, Volume = {200}, Number = {2}, Pages = {553-558}, Year = {1996}, Month = {August}, ISSN = {0033-8419}, url = {http://www.ncbi.nlm.nih.gov/pubmed/8685356}, Keywords = {Adult • Helium • Humans • Image Enhancement • Isotopes • Lung • Magnetic Resonance Imaging • Male • Middle Aged • anatomy & histology* • diagnostic use* • instrumentation • methods • methods*}, Abstract = {Two healthy volunteers who had inhaled approximately 0.75 L of laser-polarized helium-3 gas underwent magnetic resonance imaging at 1.5 T with fast gradient-echo pulse sequences and small flip angles ( < 10 degrees). Thick-section (20 mm) coronal images, time-course data (30 images collected every 1.8 seconds), and thin-section (6 mm) images were acquired. Subjects were able to breathe the gas (12% polarization) without difficulty. Thick-section images were of good quality and had a signal-to-noise ratio (S/N) of 32:1 near the surface coil and 16:1 farther away. The time images showed regional differences, which indicated potential value for quantitation. High-resolution images showed greater detail and a S/N of approximately 6:1.}, Language = {eng}, Doi = {10.1148/radiology.200.2.8685356}, Key = {fds268677} } @article{fds268681, Author = {Mugler, JP and Driehuys, B and Brookeman, JR and Cates, GD and Berr, SS and Bryant, RG and Daniel, TM and de Lange, EE and Downs, JH and Erickson, CJ and Happer, W and Hinton, DP and Kassel, NF and Maier, T and Phillips, CD and Saam, BT and Sauer, KL and Wagshul, ME}, Title = {MR imaging and spectroscopy using hyperpolarized 129Xe gas: preliminary human results.}, Journal = {Magnetic Resonance in Medicine}, Volume = {37}, Number = {6}, Pages = {809-815}, Year = {1997}, Month = {June}, ISSN = {0740-3194}, url = {http://www.ncbi.nlm.nih.gov/pubmed/9178229}, Keywords = {Adult • Brain • Female • Humans • Lung • Magnetic Resonance Imaging • Magnetic Resonance Spectroscopy • Male • Xenon Isotopes* • anatomy & histology • methods*}, Abstract = {Using a new method of xenon laser-polarization that permits the generation of liter quantities of hyperpolarized 129Xe gas, the first 129Xe imaging results from the human chest and the first 129Xe spectroscopy results from the human chest and head have been obtained. With polarization levels of approximately 2%, cross-sectional images of the lung gas-spaces with a voxel volume of 0.9 cm3 (signal-to-noise ratio (SNR), 28) were acquired and three dissolved-phase resonances in spectra from the chest were detected. In spectra from the head, one prominent dissolved-phase resonance, presumably from brain parenchyma, was detected. With anticipated improvements in the 129Xe polarization system, pulse sequences, RF coils, and breathing maneuvers, these results suggest the possibility for 129Xe gas-phase imaging of the lungs with a resolution approaching that of current conventional thoracic proton imaging. Moreover, the results suggest the feasibility of dissolved-phase imaging of both the chest and brain with a resolution similar to that obtained with the gas-phase images.}, Language = {eng}, Key = {fds268681} } @article{fds268679, Author = {Johnson, GA and Cates, G and Chen, XJ and Cofer, GP and Driehuys, B and Happer, W and Hedlund, LW and Saam, B and Shattuck, MD and Swartz, J}, Title = {Dynamics of magnetization in hyperpolarized gas MRI of the lung.}, Journal = {Magnetic Resonance in Medicine}, Volume = {38}, Number = {1}, Pages = {66-71}, Year = {1997}, Month = {July}, ISSN = {0740-3194}, url = {http://www.ncbi.nlm.nih.gov/pubmed/9211381}, Keywords = {Animals • Guinea Pigs • Helium • Isotopes • Lung • Magnetic Resonance Imaging • Male • Respiration • anatomy & histology* • diagnostic use* • methods*}, Abstract = {The magnetization in hyperpolarized gas (HP) MRI is generated by laser polarization that is independent of the magnet and imaging process. As a consequence, there is no equilibrium magnetization during the image acquisition. The competing processes of gas inflow and depolarization of the spins lead to large changes in signal as one samples k-space. A model is developed of dynamic changes in polarization of hyperpolarized 3He during infusion and in vivo imaging of the lung and verified experimentally in a live guinea pig. Projection encoding is used to measure the view-to-view variation with temporal resolution < 4 ms. Large excitation angles effectively sample the magnetization in the early stages of inflow, highlighting larger airways, while smaller excitation angles produce images of the more distal spaces. The work provides a basis for pulse sequences designed to effectively exploit HP MRI in the lung.}, Language = {eng}, Key = {fds268679} } @article{fds268669, Author = {Möller, HE and Chen, XJ and Chawla, MS and Driehuys, B and Hedlund, LW and Johnson, GA}, Title = {Signal dynamics in magnetic resonance imaging of the lung with hyperpolarized noble gases.}, Journal = {Journal of Magnetic Resonance}, Volume = {135}, Number = {1}, Pages = {133-143}, Year = {1998}, Month = {November}, ISSN = {1090-7807}, url = {http://www.ncbi.nlm.nih.gov/pubmed/9799687}, Keywords = {Animals • Guinea Pigs • Image Enhancement* • Lung • Magnetic Resonance Imaging* • Magnetics • Models, Theoretical • Noble Gases • Reproducibility of Results • anatomy & histology* • diagnostic use* • methods}, Abstract = {The nonequilibrium bulk magnetic moment of hyperpolarized (HP) noble gases generated by optical pumping has unique characteristics. Based on the Bloch equations, a model was developed describing the signal dynamics of HP gases used in magnetic resonance imaging (MRI) of the lung with special consideration to the breathing cycle. Experimental verification included extensive investigations with HP 3He and 129Xe during both inspiration and held breath in live guinea pigs. Radial acquisition was used to investigate the view variations with a temporal resolution of 5 ms. Agreement between theoretical predictions and in vivo results was excellent. Additionally, information about effects from noble gas diffusion and spin-lattice relaxation was obtained. In vivo results for T1 were 28.8 +/- 1.8 s for 3He and 31.3 +/- 1.8 s for 129Xe. Comparison with in vitro data indicated that relaxation in the pulmonary gas space is dominated by dipolar coupling with molecular oxygen. The results provide a quantitative basis for optimizing pulse sequence design in HP gas MRI of the lung.}, Language = {eng}, Doi = {10.1006/jmre.1998.1563}, Key = {fds268669} } @article{fds268663, Author = {Möller, HE and Chen, XJ and Chawla, MS and Cofer, GP and Driehuys, B and Hedlund, LW and Suddarth, SA and Johnson, GA}, Title = {Sensitivity and resolution in 3D NMR microscopy of the lung with hyperpolarized noble gases.}, Journal = {Magnetic Resonance in Medicine}, Volume = {41}, Number = {4}, Pages = {800-808}, Year = {1999}, Month = {April}, ISSN = {0740-3194}, url = {http://www.ncbi.nlm.nih.gov/pubmed/10332857}, Keywords = {Animals • Guinea Pigs • Lung • Magnetic Resonance Imaging • Microscopy • Models, Theoretical • Noble Gases • Sensitivity and Specificity • cytology* • diagnostic use* • methods*}, Abstract = {Three-dimensional magnetic resonance images of the guinea pig lung were acquired in vivo using hyperpolarized (HP) noble gases and radial projection encoding (PE). Results obtained with 3He (voxel size 17 microl) demonstrated high image quality showing airway structure down to the 5th or 6th generations. Signal-to-noise ratios (SNRs) of 129Xe images (voxel size 40 microl) were lower by about 1 order of magnitude as a consequence of the smaller gyromagnetic ratio, a more rapid relaxation in the gas reservoir, and lower polarization and isotope abundance. Comparison between experimentally obtained SNRs and results from calculations based on a model that accounts for the three-dimensional PE acquisition scheme and the non-equilibrium situation in HP gas imaging yielded excellent agreement for small flip angles. A theoretical examination of the potential resolution in HP gas MR microscopy of the lungs suggests that in vivo visualization of alveolar clusters distal to respiratory bronchioles may be possible.}, Language = {eng}, Key = {fds268663} } @article{fds268668, Author = {Möller, HE and Chawla, MS and Chen, XJ and Driehuys, B and Hedlund, LW and Wheeler, CT and Johnson, GA}, Title = {Magnetic resonance angiography with hyperpolarized 129Xe dissolved in a lipid emulsion.}, Journal = {Magnetic Resonance in Medicine}, Volume = {41}, Number = {5}, Pages = {1058-1064}, Year = {1999}, Month = {May}, ISSN = {0740-3194}, url = {http://www.ncbi.nlm.nih.gov/pubmed/10332890}, Keywords = {Abdomen • Animals • Artifacts • Blood Flow Velocity • Blood Volume • Contrast Media* • Electron Spin Resonance Spectroscopy • Fat Emulsions, Intravenous • Iliac Vein • Injections, Intravenous • Lasers • Magnetic Resonance Angiography • Magnetic Resonance Spectroscopy • Male • Pelvis • Rats • Renal Veins • Signal Processing, Computer-Assisted • Veins • Vena Cava, Inferior • Xenon Isotopes* • administration & dosage • anatomy & histology • blood supply • diagnostic use* • methods*}, Abstract = {Hyperpolarized (HP) 129Xe can be dissolved in biologically compatible lipid emulsions while maintaining sufficient polarization for in vivo vascular imaging. For xenon in Intralipid 30%, in vitro spectroscopy at 2 T yielded a chemical shift of 197 +/- 1 ppm with reference to xenon gas, a spin-lattice relaxation time T1 = 25.3 +/- 2.1 sec, and a T2* time constant of 37 +/- 5 msec. Angiograms of the abdominal and pelvic veins in the rat obtained with 129Xe MRI after intravenous injection of HP 129Xe/Intralipid 30% into the tail demonstrated signal-to-noise ratios between 8 and 29. An analysis of the inflow effect on time-of-flight images of two segments of the inferior vena cava yielded additional information. The mean blood flow velocity was 34.7 +/- 1.0 mm/sec between the junction of the caudal veins and the kidneys and 13.3 +/- 0.8 mm/sec at the position of the diaphragm. The mean volume flow rates in these segments were 7.2 +/- 3.4 ml/min and 11.0 +/- 2.8 ml/min, respectively. Intravenous delivery of HP 129Xe dissolved in a carrier may lead to novel biomedical applications of laser-polarized gases.}, Language = {eng}, Key = {fds268668} } @article{fds268664, Author = {Stith, A and Hitchens, TK and Hinton, DP and Berr, SS and Driehuys, B and Brookeman, JR and Bryant, RG}, Title = {Consequences of (129)Xe-(1)H cross relaxation in aqueous solutions.}, Journal = {Journal of Magnetic Resonance}, Volume = {139}, Number = {2}, Pages = {225-231}, Year = {1999}, Month = {August}, ISSN = {1090-7807}, url = {http://www.ncbi.nlm.nih.gov/pubmed/10423359}, Keywords = {Apoproteins • Cyclodextrins • Magnetic Resonance Spectroscopy* • Myoglobin • Protons • Solutions • Tyrosine • Water • Xenon Isotopes • analysis* • chemistry • methods}, Abstract = {We have investigated the transfer of polarization from (129)Xe to solute protons in aqueous solutions to determine the feasibility of using hyperpolarized xenon to enhance (1)H sensitivity in aqueous systems at or near room temperatures. Several solutes, each of different molecular weight, were dissolved in deuterium oxide and although large xenon polarizations were created, no significant proton signal enhancement was detected in l-tyrosine, alpha-cyclodextrin, beta-cyclodextrin, apomyoglobin, or myoglobin. Solute-induced enhancement of the (129)Xe spin-lattice relaxation rate was observed and depended on the size and structure of the solute molecule. The significant increase of the apparent spin-lattice relaxation rate of the solution phase (129)Xe by alpha-cyclodextrin and apomyoglobin indicates efficient cross relaxation. The slow relaxation of xenon in beta-cyclodextrin and l-tyrosine indicates weak coupling and inefficient cross relaxation. Despite the apparent cross-relaxation effects, all attempts to detect the proton enhancement directly were unsuccessful. Spin-lattice relaxation rates were also measured for Boltzmann (129)Xe in myoglobin. The cross-relaxation rates were determined from changes in (129)Xe relaxation rates in the alpha-cyclodextrin and myoglobin solutions. These cross-relaxation rates were then used to model (1)H signal gains for a range of (129)Xe to (1)H spin population ratios. These models suggest that in spite of very large (129)Xe polarizations, the (1)H gains will be less than 10% and often substantially smaller. In particular, dramatic (1)H signal enhancements in lung tissue signals are unlikely.}, Language = {eng}, Doi = {10.1006/jmre.1999.1781}, Key = {fds268664} } @article{fds268682, Author = {Chen, XJ and Möller, HE and Chawla, MS and Cofer, GP and Driehuys, B and Hedlund, LW and Johnson, GA}, Title = {Spatially resolved measurements of hyperpolarized gas properties in the lung in vivo. Part I: diffusion coefficient.}, Journal = {Magnetic Resonance in Medicine}, Volume = {42}, Number = {4}, Pages = {721-728}, Year = {1999}, Month = {October}, ISSN = {0740-3194}, url = {http://www.ncbi.nlm.nih.gov/pubmed/10502761}, Keywords = {Animals • Guinea Pigs • Helium • Isotopes • Lung • Magnetic Resonance Imaging • Pulmonary Diffusing Capacity • Xenon Isotopes • anatomy & histology* • diagnostic use • methods*}, Abstract = {In imaging of hyperpolarized noble gases, a knowledge of the diffusion coefficient (D) is important both as a contrast mechanism and in the design of pulse sequences. We have made diffusion coefficient maps of both hyperpolarized (3)He and (129)Xe in guinea pig lungs. Along the length of the trachea, (3)He D values were on average 2.4 cm(2)/sec, closely reproducing calculated values for free gas (2.05 cm(2)/sec). The (3)He D values measured perpendicular to the length of the trachea were approximately a factor of two less, indicating restriction to diffusion. Further evidence of restricted diffusion was seen in the distal pulmonary airspaces as the average (3)He D was 0.16 cm(2)/sec. An additional cause for the smaller (3)He D in the lung was due to the presence of air, which is composed of heavier and larger gases. The (129)Xe results show similar trends, with the trachea D averaging 0.068 cm(2)/sec and the lung D averaging 0.021 cm(2)/sec. Magn Reson Med 42:721-728, 1999.}, Language = {eng}, Key = {fds268682} } @article{fds268691, Author = {Chen, XJ and Möller, HE and Chawla, MS and Cofer, GP and Driehuys, B and Hedlund, LW and MacFall, JR and Johnson, GA}, Title = {Spatially resolved measurements of hyperpolarized gas properties in the lung in vivo. Part II: T *(2).}, Journal = {Magnetic Resonance in Medicine}, Volume = {42}, Number = {4}, Pages = {729-737}, Year = {1999}, Month = {October}, ISSN = {0740-3194}, url = {http://www.ncbi.nlm.nih.gov/pubmed/10502762}, Keywords = {Animals • Guinea Pigs • Helium • Humans • Isotopes • Lung • Magnetic Resonance Imaging • Male • Middle Aged • Pulmonary Diffusing Capacity • Trachea • Xenon Isotopes • anatomy & histology • anatomy & histology* • diagnostic use • methods*}, Abstract = {The transverse relaxation time, T *(2), of hyperpolarized (HP) gas in the lung in vivo is an important parameter for pulse sequence optimization and image contrast. We obtained T *(2) maps of HP (3)He and (129)Xe in guinea pig lungs (n = 17) and in human lungs. Eight different sets of (3)He guinea pig studies were acquired, with variation of slice selection, tidal volume, and oxygen level. For example, for a (3)He tidal volume of 3 cm(3) and no slice selection, the average T *(2) in the trachea was 14.7 ms and 8.0 ms in the intrapulmonary airspaces. The equivalent (129)Xe experiment yielded an average T *(2) of 40.8 ms in the trachea and 18.5 ms in the intrapulmonary airspaces. The average (3)He T *(2) in the human intrapulmonary airspaces was 9.4 ms. The relaxation behavior was predicted by treating the lung as a porous medium, resulting in good agreement between estimated and measured T *(2) values in the intrapulmonary airspaces. Magn Reson Med 42:729-737, 1999.}, Language = {eng}, Key = {fds268691} } @article{fds268689, Author = {Ruppert, K and Brookeman, JR and Hagspiel, KD and Driehuys, B and Mugler, JP}, Title = {NMR of hyperpolarized (129)Xe in the canine chest: spectral dynamics during a breath-hold.}, Journal = {Nmr in Biomedicine}, Volume = {13}, Number = {4}, Pages = {220-228}, Year = {2000}, Month = {June}, ISSN = {0952-3480}, url = {http://www.ncbi.nlm.nih.gov/pubmed/10867700}, Keywords = {Animals • Dogs • Female • Lung • Magnetic Resonance Imaging • Magnetic Resonance Spectroscopy • Male • Respiratory Function Tests • Respiratory Mechanics* • Time Factors • Xenon Radioisotopes* • methods • physiology*}, Abstract = {One of the major goals of hyperpolarized-gas MR imaging has been to obtain (129)Xe dissolved-phase images in humans. Since the dissolved-phase signal is much weaker than the gas-phase signal, highly optimized MR pulse sequences are required to obtain adequate images during a single breath-hold. In particular, a solid understanding of the temporal dynamics of xenon as it passes from the lung gas spaces into the parenchyma, the blood and other downstream compartments is absolutely essential. Spectroscopy experiments were performed in the canine chest to elucidate the behavior of xenon exchange in the lung. The experiments covered a time range from 1 ms to 9 s and therefore considerably extend the data currently available in the literature. It was found that the integrals of the dissolved-phase resonances approached plateau values within approximately 200 ms, and then increased again after approximately 1 s. This behavior suggests an early saturation of the parenchyma before xenon reaches downstream compartments. Mono-exponential recovery curves with time constants on the order of 100 ms were fit to the data. These results potentially provide information on several underlying physiological parameters of the lung, including the parenchymal and blood volumes as well as the diffusion properties of lung tissue.}, Language = {eng}, Key = {fds268689} } @article{fds311297, Author = {Chann, B and Nelson, IA and Anderson, LW and Driehuys, B and Walker, TG}, Title = {Xe-129-Xe molecular spin relaxation}, Journal = {Physical Review Letters}, Volume = {88}, Number = {11}, Year = {2002}, Month = {March}, ISSN = {0031-9007}, url = {http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000174541700011&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=47d3190e77e5a3a53558812f597b0b92}, Doi = {10.1103/PhysRevLett.88.113201}, Key = {fds311297} } @article{fds268645, Author = {Jacob, RE and Driehuys, B and Saam, B}, Title = {Fundamental mechanisms of 3He relaxation on glass}, Journal = {Chemical Physics Letters}, Volume = {370}, Number = {1-2}, Pages = {261-267}, Year = {2003}, url = {http://dx.doi.org/10.1016/S0009-2614(03)00110-6}, Abstract = {We present a model of 3He relaxation on the surface of borosilicate glass which accurately predicts observed relaxation rates and their temperature dependence. Above room temperature 3He dissolves into Pyrex, where interactions with Fe3+ ions result in a relaxation time of ≈1 ms. Gas exchange across the glass surface of an enclosed vessel leads to T1-1 = A/V (3.9 ± 1.4) × 10-2 cm/h at room temperature, where A/V is the surface-to-volume ratio. The activation energy for relaxation is 13.7 ± 0.7 kJ/mol and is dominated by the activation energy of 3He diffusion in glass. This is the first successful confirmation of predicted 3He relaxation rates in glass vessels. © 2003 Elsevier Science B.V. All rights reserved.}, Doi = {10.1016/S0009-2614(03)00110-6}, Key = {fds268645} } @article{fds268690, Author = {Babcock, E and Nelson, I and Kadlecek, S and Driehuys, B and Anderson, LW and Hersman, FW and Walker, TG}, Title = {Hybrid spin-exchange optical pumping of 3He.}, Journal = {Physical Review Letters}, Volume = {91}, Number = {12}, Pages = {123003}, Year = {2003}, Month = {September}, ISSN = {0031-9007}, url = {http://www.ncbi.nlm.nih.gov/pubmed/14525358}, Abstract = {We demonstrate spin-exchange optical pumping of 3He using a "hybrid" K-Rb vapor mixture. The Rb atoms absorb light from a standard laser at 795 nm, then collisionally polarize the potassium atoms. Spin-exchange collisions of K and 3He atoms then transfer the angular momentum to the 3He with much greater efficiency than Rb-3He. For a K-rich vapor, the efficiency of the hybrid spin-exchange collisions approaches 1/4, an order of magnitude greater than achieved by pure Rb pumping. We present the first measurements of actual photon efficiencies (polarized nuclei produced per absorbed photon), and show that a new parasitic absorption process limits the total efficiencies for both hybrid and pure Rb pumping.}, Language = {eng}, Doi = {10.1103/PhysRevLett.91.123003}, Key = {fds268690} } @article{fds268686, Author = {Månsson, S and Wolber, J and Driehuys, B and Wollmer, P and Golman, K}, Title = {Characterization of diffusing capacity and perfusion of the rat lung in a lipopolysaccaride disease model using hyperpolarized 129Xe.}, Journal = {Magnetic Resonance in Medicine}, Volume = {50}, Number = {6}, Pages = {1170-1179}, Year = {2003}, Month = {December}, ISSN = {0740-3194}, url = {http://www.ncbi.nlm.nih.gov/pubmed/14648564}, Keywords = {Animals • Capillary Permeability • Lipopolysaccharides • Magnetic Resonance Spectroscopy* • Male • Pulmonary Alveoli • Pulmonary Circulation* • Pulmonary Diffusing Capacity* • Rats • Rats, Wistar • Respiratory Distress Syndrome, Adult • Xenon Isotopes • chemically induced • diagnosis • diagnostic use* • physiopathology • physiopathology*}, Abstract = {The ability to quantify pulmonary diffusing capacity and perfusion using dynamic hyperpolarized (129)Xe NMR spectroscopy is demonstrated. A model of alveolar gas exchange was developed, which, in conjunction with (129)Xe NMR, enables quantification of average alveolar wall thickness, pulmonary perfusion, capillary diffusion length, and mean transit time. The technique was employed to compare a group of naïve rats (n = 10) with a group of rats with acute inflammatory lung injury (n = 10), caused by instillation of lipopolysaccaride (LPS). The measured structural and perfusion-related parameters were in agreement with reported values from studies using non-NMR methods. Significant differences between the groups were found in total diffusion length (control 8.5 +/- 0.5 microm, LPS 9.9 +/- 0.6 microm, P < 0.001), in capillary diffusion length (control 2.9 +/- 0.4 microm, LPS 3.9 +/- 1.0 microm, P < 0.05), and in pulmonary hematocrit (control 0.55 +/- 0.06, LPS 0.43 +/- 0.08, P < 0.01), whereas no differences were observed in alveolar wall thickness, pulmonary perfusion, and mean transit time. These results demonstrate the ability of the method to distinguish two main aspects of lung function, namely, diffusing capacity and pulmonary perfusion.}, Language = {eng}, Doi = {10.1002/mrm.10649}, Key = {fds268686} } @article{fds268675, Author = {Spector, ZZ and Emami, K and Fischer, MC and Zhu, J and Ishii, M and Yu, J and Kadlecek, S and Driehuys, B and Panettieri, RA and Lipson, DA and Gefter, W and Shrager, J and Rizi, RR}, Title = {A small animal model of regional alveolar ventilation using HP 3He MRI1.}, Journal = {Academic Radiology}, Volume = {11}, Number = {10}, Pages = {1171-1179}, Year = {2004}, Month = {October}, ISSN = {1076-6332}, url = {http://www.ncbi.nlm.nih.gov/pubmed/15530811}, Keywords = {Animals • Helium • Isotopes • Magnetic Resonance Imaging • Male • Models, Animal • Pulmonary Alveoli • Pulmonary Ventilation • Rats • Rats, Sprague-Dawley • anatomy & histology* • diagnostic use • diagnostic use* • methods* • physiology}, Abstract = {RATIONALE AND OBJECTIVES: The aim of this study was to establish a standardized procedure for the measurement of regional fractional ventilation in a healthy rat model as a baseline for further studies of pulmonary disorder models. MATERIALS AND METHODS: The lungs of five healthy male Sprague-Dawley rats were imaged using hyperpolarized helium-3 magnetic resonance imaging. From these images, regional fractional ventilation was calculated and maps generated detailing the distribution of fractional ventilation in the lung. The 1.56 mm x 1.56 mm x 4 mm regions of interest were assigned on 5 cm x 5 cm field of view lung maps. Histograms were also generated showing the frequency distribution of fractional ventilation values. To compare fractional ventilation values between animals, the ventilation procedure was standardized to results from individual pulmonary function tests. Each animal's spontaneous tidal volume, respiratory rate, and inspiration percentage (percent of total respiratory cycle in inspiration) were used in their mechanical ventilation settings. RESULTS: Results were similar among all five healthy rats based on examination of ventilation distribution maps and frequency distribution histograms. Mean (0.13) and standard deviation (0.07) were calculated for fractional ventilation in each animal. However, these values were determined to be influenced by slice selection, and therefore the maps and histograms were favored in analysis of results. CONCLUSION: This study shows consistent results in healthy rat lungs and will serve as a baseline study for future measurements in emphysematous rat lungs.}, Language = {eng}, Doi = {10.1016/j.acra.2004.08.001}, Key = {fds268675} } @article{fds268635, Author = {Driehuys, B and Raidy, T and Pollaro, J and Johnson, A and Dewhirst, M and Marks, L and Vujaskovic, Z}, Title = {Hyperpolarized 129Xe MRI for functional assessment of radiation-induced lung injury}, Journal = {International Journal of Radiation Oncology, Biology, Physics}, Volume = {63}, Number = {2}, Pages = {S460-S461}, Year = {2005}, ISSN = {0360-3016}, url = {http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000232083301298&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=47d3190e77e5a3a53558812f597b0b92}, Doi = {10.1016/j.ijrobp.2005.07.784}, Key = {fds268635} } @article{fds268673, Author = {Spector, ZZ and Emami, K and Fischer, MC and Zhu, J and Ishii, M and Vahdat, V and Yu, J and Kadlecek, S and Driehuys, B and Lipson, DA and Gefter, W and Shrager, J and Rizi, RR}, Title = {Quantitative assessment of emphysema using hyperpolarized 3He magnetic resonance imaging.}, Journal = {Magnetic Resonance in Medicine}, Volume = {53}, Number = {6}, Pages = {1341-1346}, Year = {2005}, Month = {June}, ISSN = {0740-3194}, url = {http://www.ncbi.nlm.nih.gov/pubmed/15906306}, Keywords = {Animals • Disease Models, Animal • Helium • Image Processing, Computer-Assisted • Isotopes • Magnetic Resonance Imaging • Male • Pancreatic Elastase • Pulmonary Emphysema • Pulmonary Ventilation • Rats • Rats, Sprague-Dawley • diagnostic use • diagnostic use* • methods* • physiopathology*}, Abstract = {In this experiment, Sprague-Dawley rats with elastase-induced emphysema were imaged using hyperpolarized (3)He MRI. Regional fractional ventilation r, the fraction of gas replaced with a single tidal breath, was calculated from a series of images in a wash-in study of hyperpolarized gas. We compared the regional fractional ventilation in these emphysematous rats to the regional fractional ventilations we calculated from a previous baseline study in healthy Sprague-Dawley rats. We found that there were differences in the maps of fractional ventilation and its associated frequency distribution between the healthy and emphysematous rat lungs. Fractional ventilation tended to be much lower in emphysematous rats than in normal rats. With this information, we can use data on fractional ventilation to regionally distinguish between healthy and emphysematous portions of the lung. The successful implementation of such a technique on a rat model could lead to work toward the future implementation of this technique in human patients.}, Language = {eng}, Doi = {10.1002/mrm.20514}, Key = {fds268673} } @article{fds268683, Author = {Driehuys, B}, Title = {Chemistry: Toward molecular imaging with xenon MRI}, Journal = {Science}, Volume = {314}, Number = {5798}, Pages = {432-433}, Year = {2006}, Month = {October}, ISSN = {0036-8075}, url = {http://www.ncbi.nlm.nih.gov/pubmed/17053138}, Keywords = {Animals • Atherosclerosis • Biosensing Techniques* • Humans • Lung • Magnetic Resonance Imaging • Magnetic Resonance Spectroscopy • Rats • Sensitivity and Specificity • Xenon Isotopes* • anatomy & histology • diagnosis • methods* • physiopathology}, Language = {eng}, Doi = {10.1126/science/1134532}, Key = {fds268683} } @article{fds268661, Author = {Driehuys, B and Cofer, GP and Pollaro, J and Mackel, JB and Hedlund, LW and Johnson, GA}, Title = {Imaging alveolar-capillary gas transfer using hyperpolarized 129Xe MRI.}, Journal = {Proceedings of the National Academy of Sciences of USA}, Volume = {103}, Number = {48}, Pages = {18278-18283}, Year = {2006}, Month = {November}, ISSN = {0027-8424}, url = {http://www.ncbi.nlm.nih.gov/pubmed/17101964}, Keywords = {Animals • Erythrocytes • Magnetic Resonance Imaging • Microcirculation • Oxygen • Rats • Rats, Inbred F344 • Respiration* • Xenon Isotopes • metabolism • metabolism* • methods*}, Abstract = {Effective pulmonary gas exchange relies on the free diffusion of gases across the thin tissue barrier separating airspace from the capillary red blood cells (RBCs). Pulmonary pathologies, such as inflammation, fibrosis, and edema, which cause an increased blood-gas barrier thickness, impair the efficiency of this exchange. However, definitive assessment of such gas-exchange abnormalities is challenging, because no methods currently exist to directly image the gas transfer process. Here we exploit the solubility and chemical shift of (129)Xe, the magnetic resonance signal of which has been enhanced by 10(5) with hyperpolarization, to differentially image its transfer from the airspaces into the tissue barrier spaces and RBCs in the gas exchange regions of the lung. Based on a simple diffusion model, we estimate that this MR imaging method for measuring (129)Xe alveolar-capillary transfer is sensitive to changes in blood-gas barrier thickness of approximately 5 microm. We validate the successful separation of tissue barrier and RBC images and show the utility of this method in a rat model of pulmonary fibrosis where (129)Xe replenishment of the RBCs is severely impaired in regions of lung injury.}, Language = {eng}, Doi = {10.1073/pnas.0608458103}, Key = {fds268661} } @article{fds268676, Author = {Driehuys, B and Hedlund, LW}, Title = {Imaging techniques for small animal models of pulmonary disease: MR microscopy.}, Journal = {Toxicologic Pathology (Sage)}, Volume = {35}, Number = {1}, Pages = {49-58}, Year = {2007}, Month = {January}, ISSN = {0192-6233}, url = {http://www.ncbi.nlm.nih.gov/pubmed/17325972}, Keywords = {Animals • Disease Models, Animal* • Helium • Isotopes • Lung • Lung Diseases • Magnetic Resonance Imaging • Mice • Microscopy* • Rats • Respiratory Function Tests • Xenon Isotopes • diagnosis* • diagnostic use • instrumentation • methods • methods* • pathology* • physiopathology}, Abstract = {In vivo magnetic resonance microscopy (MRM) of the small animal lung has become a valuable research tool, especially for preclinical studies. MRM offers a noninvasive and nondestructive tool for imaging small animals longitudinally and at high spatial resolution. We summarize some of the technical and biologic problems and solutions associated with imaging the small animal lung and describe several important pulmonary disease applications. A major advantage of MR is direct imaging of the gas spaces of the lung using breathable gases such as helium and xenon. When polarized, these gases become rich MR signal sources. In animals breathing hyperpolarized helium, the dynamics of gas distribution can be followed and airway constrictions and obstructions can be detected. Diffusion coefficients of helium can be calculated from diffusion-sensitive images, which can reveal micro-structural changes in the lungs associated with pathologies such as emphysema and fibrosis. Unlike helium, xenon in the lung is absorbed by blood and exhibits different frequencies in gas, tissue, or erythrocytes. Thus, with MR imaging, the movement of xenon gas can be tracked through pulmonary compartments to detect defects of gas transfer. MRM has become a valuable tool for studying morphologic and functional changes in small animal models of lung diseases.}, Language = {eng}, Doi = {10.1080/01926230601132048}, Key = {fds268676} } @article{fds268667, Author = {Driehuys, B and Walker, J and Pollaro, J and Cofer, GP and Mistry, N and Schwartz, D and Johnson, GA}, Title = {3He MRI in mouse models of asthma.}, Journal = {Magnetic Resonance in Medicine}, Volume = {58}, Number = {5}, Pages = {893-900}, Year = {2007}, Month = {November}, ISSN = {0740-3194}, url = {http://www.ncbi.nlm.nih.gov/pubmed/17969115}, Keywords = {Animals • Asthma • Disease Models, Animal* • Helium • Magnetic Resonance Imaging • Mice • Mice, Inbred BALB C • Mice, Inbred C57BL • methods* • pathology*}, Abstract = {In the study of asthma, a vital role is played by mouse models, because knockout or transgenic methods can be used to alter disease pathways and identify therapeutic targets that affect lung function. Assessment of lung function in rodents by available methods is insensitive because these techniques lack regional specificity. A more sensitive method for evaluating lung function in human asthma patients uses hyperpolarized (HP) (3)He MRI before and after bronchoconstriction induced by methacholine (MCh). We now report the ability to perform such (3)He imaging of MCh response in mice, where voxels must be approximately 3000 times smaller than in humans and (3)He diffusion becomes an impediment to resolving the airways. We show three-dimensional (3D) images that reveal airway structure down to the fifth branching and visualize ventilation at a resolution of 125 x 125 x 1000 microm(3). Images of ovalbumin (OVA)-sensitized mice acquired after MCh show both airway closure and ventilation loss. To also observe the MCh response in naive mice, we developed a non-slice-selective 2D protocol with 187 x 187 microm(2) resolution that was fast enough to record the MCh response and recovery with 12-s temporal resolution. The extension of (3)He MRI to mouse models should make it a valuable translational tool in asthma research.}, Language = {eng}, Doi = {10.1002/mrm.21306}, Key = {fds268667} } @article{fds268647, Author = {Couture, AH and Clegg, TB and Driehuys, B}, Title = {Pressure shifts and broadening of the Cs D1 and D2 lines by He, N2, and Xe at densities used for optical pumping and spin exchange polarization}, Journal = {Journal of Applied Physics}, Volume = {104}, Number = {9}, Year = {2008}, ISSN = {0021-8979}, url = {http://dx.doi.org/10.1063/1.3018181}, Abstract = {The production of hyperpolarized gases by spin-exchange optical pumping (SEOP) requires exact knowledge of the alkali metal's D1 absorption profile and the degree to which it is broadened and shifted by varying buffer gas composition and pressure. We have measured these parameters for cesium (Cs) in the presence of Xe, N2, and H4 e perturber gases at densities up to 10 amagats. The effects of these gases are important as Cs is attracting increasing interest for SEOP applications. Our measurements were made using simple white-light illumination of the Cs vapor while characterizing the D1 (6 S1/2 to 6 P1/2) and D2 (6 S1/2 to 6 P3/2) resonances using a high-resolution optical spectrometer. For the Cs D1 resonance at T=120 °C, we report shifts from the 894.59 nm vacuum wavelength caused by H3 e, H4 e, N2, and Xe of -0.017±0.003, -0.013±0.002, 0.026±0.002, and 0.029±0.002 nm/amagat. We also report the shifts for the D2 resonance as well as pressure broadening coefficients for both resonances. © 2008 American Institute of Physics.}, Doi = {10.1063/1.3018181}, Key = {fds268647} } @article{fds268684, Author = {Driehuys, B and Nouls, J and Badea, A and Bucholz, E and Ghaghada, K and Petiet, A and Hedlund, LW}, Title = {Small animal imaging with magnetic resonance microscopy.}, Journal = {ILAR Journal}, Volume = {49}, Number = {1}, Pages = {35-53}, Year = {2008}, ISSN = {1084-2020}, url = {http://www.ncbi.nlm.nih.gov/pubmed/18172332}, Keywords = {Animals • Disease Models, Animal • Magnetic Resonance Imaging • Mice • Microscopy • Rats • instrumentation • methods*}, Abstract = {Small animal magnetic resonance microscopy (MRM) has evolved significantly from testing the boundaries of imaging physics to its expanding use today as a tool in noninvasive biomedical investigations. MRM now increasingly provides functional information about living animals, with images of the beating heart, breathing lung, and functioning brain. Unlike clinical MRI, where the focus is on diagnosis, MRM is used to reveal fundamental biology or to noninvasively measure subtle changes in the structure or function of organs during disease progression or in response to experimental therapies. High-resolution anatomical imaging reveals increasingly exquisite detail in healthy animals and subtle architectural aberrations that occur in genetically altered models. Resolution of 100 mum in all dimensions is now routinely attained in living animals, and (10 mum)(3) is feasible in fixed specimens. Such images almost rival conventional histology while allowing the object to be viewed interactively in any plane. In this review we describe the state of the art in MRM for scientists who may be unfamiliar with this modality but who want to apply its capabilities to their research. We include a brief review of MR concepts and methods of animal handling and support, before covering a range of MRM applications-including the heart, lung, and brain-and the emerging field of MR histology. The ability of MRM to provide a detailed functional and anatomical picture in rats and mice, and to track this picture over time, makes it a promising platform with broad applications in biomedical research.}, Language = {eng}, Doi = {10.1093/ilar.49.1.35}, Key = {fds268684} } @article{fds268666, Author = {Driehuys, B and Pollaro, J and Cofer, GP}, Title = {In vivo MRI using real-time production of hyperpolarized 129Xe.}, Journal = {Magnetic Resonance in Medicine}, Volume = {60}, Number = {1}, Pages = {14-20}, Year = {2008}, Month = {July}, ISSN = {0740-3194}, url = {http://www.ncbi.nlm.nih.gov/pubmed/18581406}, Keywords = {Animals • Computer Systems • Magnetic Resonance Imaging* • Rats • Rats, Inbred F344 • Spectrum Analysis • Xenon Isotopes* • diagnostic use}, Abstract = {MR imaging of hyperpolarized (HP) nuclei is challenging because they are typically delivered in a single dose of nonrenewable magnetization, from which the entire image must be derived. This problem can be overcome with HP (129)Xe, which can be produced sufficiently rapidly to deliver in dilute form (1%) continuously and on-demand. We demonstrate a real-time in vivo delivery of HP (129)Xe mixture to rats, a capability we now routinely use for setting frequency, transmitter gain, shimming, testing pulse sequences, scout imaging, and spectroscopy. Compared to images acquired using conventional fully concentrated (129)Xe, real-time (129)Xe images have 26-fold less signal, but clearly depict ventilation abnormalities. Real-time (129)Xe MRI could be useful for time-course studies involving acute injury or response to treatment. Ultimately, real-time (129)Xe MRI could be done with more highly concentrated (129)Xe, which could increase the signal-to-noise ratio by 100 relative to these results to enable a new class of gas imaging applications.}, Language = {eng}, Doi = {10.1002/mrm.21651}, Key = {fds268666} } @article{fds268687, Author = {Brown, RH and Irvin, CG and Allen, GB and Shapiro, SD and Martin, WJ and Kolb, MRJ and Hyde, DM and Nieman, GF and Cody, DD and Ishii, M and Kadlecek, SJ and Driehuys, B and Rizi, RR and Wu, AM and Weber, WA and Stout, DB and ATS Small Animal Imaging Subcommittee}, Title = {An official ATS conference proceedings: advances in small-animal imaging application to lung pathophysiology.}, Journal = {Proceedings of the American Thoracic Society}, Volume = {5}, Number = {5}, Pages = {591-600}, Year = {2008}, Month = {July}, ISSN = {1546-3222}, url = {http://www.ncbi.nlm.nih.gov/pubmed/18625751}, Keywords = {Animals • Congresses as Topic* • Diagnostic Imaging • Disease Models, Animal • Lung Diseases • Reproducibility of Results • Respiration* • diagnosis* • methods* • physiopathology*}, Language = {eng}, Doi = {10.1513/pats.200708-116ST}, Key = {fds268687} } @article{fds268674, Author = {Thomas, AC and Potts, EN and Chen, BT and Slipetz, DM and Foster, WM and Driehuys, B}, Title = {A robust protocol for regional evaluation of methacholine challenge in mouse models of allergic asthma using hyperpolarized 3He MRI.}, Journal = {Nmr in Biomedicine}, Volume = {22}, Number = {5}, Pages = {502-515}, Year = {2009}, Month = {June}, ISSN = {1099-1492}, url = {http://www.ncbi.nlm.nih.gov/pubmed/19204996}, Keywords = {Animals • Asthma • Bronchoalveolar Lavage Fluid • Bronchoconstriction • Cell Count • Disease Models, Animal • Drug Delivery Systems • Heart Rate • Helium • Imaging, Three-Dimensional • Infusion Pumps • Lung • Magnetic Resonance Imaging • Methacholine Chloride • Mice • Ovalbumin • Pulmonary Ventilation • Reproducibility of Results • Time Factors • administration & dosage • administration & dosage* • chemistry* • cytology • drug effects • methods* • pathology • pathology* • pharmacology* • physiopathology}, Abstract = {Hyperpolarized (HP) (3)He magnetic resonance imaging has been recently used to produce high-resolution images of pulmonary ventilation after methacholine (MCh) challenge in mouse models of allergic inflammation. This capability presents an opportunity to gain new insights about these models and to more sensitively evaluate new drug treatments in the pre-clinical setting. In the current study, we present our initial experience using two-dimensional (2D), time-resolved (3)He MRI of MCh challenge-induced airways hyperreactivity (AHR) to compare ovalbumin-sensitized and challenged (N = 8) mice to controls (N = 8). Imaging demonstrated that ovalbumin-sensitized and challenged animals exhibited many large ventilation defects even prior to MCh challenge (four out of eight) compared to no defects in the control animals. Additionally, the ovalbumin-sensitized and challenged animals experienced a greater number of ventilation defects (4.5 +/- 0.4) following MCh infusion than did controls (3.3 +/- 0.6). However, due to variability in MCh delivery that was specific to the small animal MRI environment, the difference in mean defect number was not statistically significant. These findings are reviewed in detail and a comprehensive solution to the variability problem is presented that has greatly enhanced the magnitude and reproducibility of the MCh response. This has permitted us to develop a new imaging protocol consisting of a baseline 3D image, a time-resolved 2D series during MCh challenge, and a post-MCh 3D image that reveals persistent ventilation defects.}, Language = {eng}, Doi = {10.1002/nbm.1362}, Key = {fds268674} } @article{fds268680, Author = {Driehuys, B and Moeller, HE and Cleveland, ZI and Pollaro, J and Hedlund, LW}, Title = {Pulmonary Perfusion and Xenon Gas Exchange in Rats: MR Imaging with Intravenous Injection of Hyperpolarized (129)Xe}, Journal = {Radiology}, Volume = {252}, Number = {2}, Pages = {386-393}, Year = {2009}, Month = {August}, ISSN = {0033-8419}, url = {http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000268875900011&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=47d3190e77e5a3a53558812f597b0b92}, Abstract = {Purpose: To develop and demonstrate a method for regional evaluation of pulmonary perfusion and gas exchange based on intravenous injection of hyperpolarized xenon 129 ((129)Xe) and subsequent magnetic resonance (MR) imaging of the gas-phase (129)Xe emerging in the alveolar airspaces. Materials and Methods: Five Fischer 344 rats that weighed 200-425 g were prepared for imaging according to an institutional animal care and use committee-approved protocol. Rats were ventilated, and a 3-F catheter was placed in the jugular (n = 1) or a 24-gauge catheter in the tail (n = 4) vein. Imaging and spectroscopy of gas-phase (129)Xe were performed after injecting 5 mL of half-normal saline saturated with (129)Xe hyperpolarized to 12%. Corresponding ventilation images were obtained during conventional inhalation delivery of hyperpolarized (129)Xe. Results: Injections of (129)Xe-saturated saline were well tolerated and produced a strong gas-phase (129)Xe signal in the airspaces that resulted from (129)Xe transport through the pulmonary circulation and diffusion across the blood-gas barrier. After a single injection, the emerging (129)Xe gas could be detected separately from (129)Xe remaining in the blood and was imaged with an in-plane resolution of 1 x 1 mm and a signal-to-noise ratio of 25. Images in one rat revealed a matched ventilation-perfusion deficit, while images in another rat showed that xenon gas exchange was temporarily impaired after saline overload, with recovery of function 1 hour later. Conclusion: MR imaging of gas-phase (129)Xe emerging in the pulmonary airspaces after intravenous injection has the potential to become a sensitive and minimally invasive new tool for regional evaluation of pulmonary perfusion and gas exchange. Supplemental material: http://radiology.rsnajnls.org/cgi/content/full/2513081550/DC1 (c) RSNA, 2009.}, Language = {ENG}, Doi = {10.1148/radiol.2513081550}, Key = {fds268680} } @article{fds268692, Author = {Driehuys, B and Möller, HE and Cleveland, ZI and Pollaro, J and Hedlund, LW}, Title = {Pulmonary perfusion and xenon gas exchange in rats: MR imaging with intravenous injection of hyperpolarized 129Xe.}, Journal = {Radiology}, Volume = {252}, Number = {2}, Pages = {386-393}, Year = {2009}, Month = {August}, ISSN = {1527-1315}, url = {http://www.ncbi.nlm.nih.gov/pubmed/19703880}, Keywords = {Animals • Contrast Media • Image Interpretation, Computer-Assisted • Magnetic Resonance Imaging • Physician's Practice Patterns • Pulmonary Alveoli • Pulmonary Circulation • Pulmonary Gas Exchange • Rats • Rats, Inbred F344 • Science • Technology Transfer • Xenon Isotopes • administration & dosage • diagnostic use* • methods* • pharmacokinetics • pharmacokinetics* • physiology* • trends}, Abstract = {PURPOSE: To develop and demonstrate a method for regional evaluation of pulmonary perfusion and gas exchange based on intravenous injection of hyperpolarized xenon 129 ((129)Xe) and subsequent magnetic resonance (MR) imaging of the gas-phase (129)Xe emerging in the alveolar airspaces. MATERIALS AND METHODS: Five Fischer 344 rats that weighed 200-425 g were prepared for imaging according to an institutional animal care and use committee-approved protocol. Rats were ventilated, and a 3-F catheter was placed in the jugular (n = 1) or a 24-gauge catheter in the tail (n = 4) vein. Imaging and spectroscopy of gas-phase (129)Xe were performed after injecting 5 mL of half-normal saline saturated with (129)Xe hyperpolarized to 12%. Corresponding ventilation images were obtained during conventional inhalation delivery of hyperpolarized (129)Xe. RESULTS: Injections of (129)Xe-saturated saline were well tolerated and produced a strong gas-phase (129)Xe signal in the airspaces that resulted from (129)Xe transport through the pulmonary circulation and diffusion across the blood-gas barrier. After a single injection, the emerging (129)Xe gas could be detected separately from (129)Xe remaining in the blood and was imaged with an in-plane resolution of 1 x 1 mm and a signal-to-noise ratio of 25. Images in one rat revealed a matched ventilation-perfusion deficit, while images in another rat showed that xenon gas exchange was temporarily impaired after saline overload, with recovery of function 1 hour later. CONCLUSION: MR imaging of gas-phase (129)Xe emerging in the pulmonary airspaces after intravenous injection has the potential to become a sensitive and minimally invasive new tool for regional evaluation of pulmonary perfusion and gas exchange. SUPPLEMENTAL MATERIAL: http://radiology.rsnajnls.org/cgi/content/full/2513081550/DC1.}, Language = {eng}, Doi = {10.1148/radiol.2513081550}, Key = {fds268692} } @article{fds268685, Author = {Cleveland, ZI and Möller, HE and Hedlund, LW and Driehuys, B}, Title = {Continuously infusing hyperpolarized 129Xe into flowing aqueous solutions using hydrophobic gas exchange membranes.}, Journal = {The Journal of Physical Chemistry Part B: Condensed Matter, Materials, Surfaces, Interfaces and Biophysical}, Volume = {113}, Number = {37}, Pages = {12489-12499}, Year = {2009}, Month = {September}, ISSN = {1520-6106}, url = {http://www.ncbi.nlm.nih.gov/pubmed/19702286}, Keywords = {Animals • Hydrophobic and Hydrophilic Interactions • Magnetic Resonance Imaging • Magnetic Resonance Spectroscopy • Magnetics • Male • Membranes, Artificial* • Rats • Solutions • Time Factors • Water • Xenon • blood • chemistry*}, Abstract = {Hyperpolarized (HP) (129)Xe yields high signal intensities in nuclear magnetic resonance (NMR) and, through its large chemical shift range of approximately 300 ppm, provides detailed information about the local chemical environment. To exploit these properties in aqueous solutions and living tissues requires the development of methods for efficiently dissolving HP (129)Xe over an extended time period. To this end, we have used commercially available gas exchange modules to continuously infuse concentrated HP (129)Xe into flowing liquids, including rat whole blood, for periods as long as one hour and have demonstrated the feasibility of dissolved-phase MR imaging with submillimeter resolution within minutes. These modules, which exchange gases using hydrophobic microporous polymer membranes, are compatible with a variety of liquids and are suitable for infusing HP (129)Xe into the bloodstream in vivo. Additionally, we have developed a detailed mathematical model of the infused HP (129)Xe signal dynamics that should be useful in designing improved infusion systems that yield even higher dissolved HP (129)Xe signal intensities.}, Language = {eng}, Doi = {10.1021/jp9049582}, Key = {fds268685} } @article{fds268671, Author = {Branca, RT and Cleveland, ZI and Fubara, B and Kumar, CSSR and Maronpot, RR and Leuschner, C and Warren, WS and Driehuys, B}, Title = {Molecular MRI for sensitive and specific detection of lung metastases.}, Journal = {Proceedings of the National Academy of Sciences of USA}, Volume = {107}, Number = {8}, Pages = {3693-3697}, Year = {2010}, Month = {February}, ISSN = {1091-6490}, url = {http://www.ncbi.nlm.nih.gov/pubmed/20142483}, Keywords = {Adenocarcinoma • Animals • Breast Neoplasms • Female • Ferric Compounds • Helium • Humans • Isotopes • Lung Neoplasms • Magnetic Resonance Imaging • Male • Mice • Mice, Nude • Nanoparticles • diagnosis* • diagnostic use • methods* • pathology* • secondary*}, Abstract = {Early and specific detection of metastatic cancer cells in the lung (the most common organ targeted by metastases) could significantly improve cancer treatment outcomes. However, the most widespread lung imaging methods use ionizing radiation and have low sensitivity and/or low specificity for cancer cells. Here we address this problem with an imaging method to detect submillimeter-sized metastases with molecular specificity. Cancer cells are targeted by iron oxide nanoparticles functionalized with cancer-binding ligands, then imaged by high-resolution hyperpolarized (3)He MRI. We demonstrate in vivo detection of pulmonary micrometastates in mice injected with breast adenocarcinoma cells. The method not only holds promise for cancer imaging but more generally suggests a fundamentally unique approach to molecular imaging in the lungs.}, Language = {eng}, Doi = {10.1073/pnas.1000386107}, Key = {fds268671} } @article{fds268655, Author = {Mistry, NN and Thomas, A and Kaushik, SS and Johnson, GA and Driehuys, B}, Title = {Quantitative analysis of hyperpolarized 3He ventilation changes in mice challenged with methacholine.}, Journal = {Magnetic Resonance in Medicine}, Volume = {63}, Number = {3}, Pages = {658-666}, Year = {2010}, Month = {March}, ISSN = {1522-2594}, url = {http://www.ncbi.nlm.nih.gov/pubmed/20187176}, Keywords = {Administration, Inhalation • Algorithms* • Animals • Asthma • Contrast Media • Helium • Image Enhancement • Isotopes • Magnetic Resonance Imaging • Methacholine Chloride • Mice • Mice, Inbred C57BL • Reproducibility of Results • Sensitivity and Specificity • administration & dosage • diagnosis* • diagnostic use • diagnostic use* • methods*}, Abstract = {The capability to use high-resolution (3)He MRI to depict regional ventilation changes and airway narrowing in mice challenged with methacholine (MCh) offers the opportunity to gain new insights into the study of asthma. However, to fully exploit the value of this novel technique, it is important to move beyond visual inspection of the images toward automated and quantitative analysis. To address this gap, we describe a postprocessing approach to create ventilation difference maps to better visualize and quantify regional ventilation changes before and after MCh challenge. We show that difference maps reveal subtle changes in airway caliber, and highlight both focal and diffuse regional alterations in ventilation. Ventilation changes include both hypoventilation and compensatory areas of hyperventilation. The difference maps can be quantified by a histogram plot of the ventilation changes, in which the standard deviation increases with MCh dose (R(2) = 0.89). This method of analysis is shown to be more sensitive than simple threshold-based detection of gross ventilation defects.}, Language = {eng}, Doi = {10.1002/mrm.22311}, Key = {fds268655} } @article{fds268653, Author = {Cleveland, ZI and Cofer, GP and Metz, G and Beaver, D and Nouls, J and Kaushik, SS and Kraft, M and Wolber, J and Kelly, KT and McAdams, HP and Driehuys, B}, Title = {Hyperpolarized Xe MR imaging of alveolar gas uptake in humans.}, Journal = {PloS one}, Volume = {5}, Number = {8}, Pages = {e12192}, Year = {2010}, Month = {August}, ISSN = {1932-6203}, url = {http://www.ncbi.nlm.nih.gov/pubmed/20808950}, Keywords = {Adult • Artifacts • Blood Volume • Feasibility Studies • Humans • Imaging, Three-Dimensional • Magnetic Resonance Imaging • Middle Aged • Pulmonary Alveoli • Pulmonary Gas Exchange* • Respiration • Time Factors • Xenon Isotopes • Young Adult • diagnostic use • methods* • physiology*}, Abstract = {BACKGROUND: One of the central physiological functions of the lungs is to transfer inhaled gases from the alveoli to pulmonary capillary blood. However, current measures of alveolar gas uptake provide only global information and thus lack the sensitivity and specificity needed to account for regional variations in gas exchange. METHODS AND PRINCIPAL FINDINGS: Here we exploit the solubility, high magnetic resonance (MR) signal intensity, and large chemical shift of hyperpolarized (HP) (129)Xe to probe the regional uptake of alveolar gases by directly imaging HP (129)Xe dissolved in the gas exchange tissues and pulmonary capillary blood of human subjects. The resulting single breath-hold, three-dimensional MR images are optimized using millisecond repetition times and high flip angle radio-frequency pulses, because the dissolved HP (129)Xe magnetization is rapidly replenished by diffusive exchange with alveolar (129)Xe. The dissolved HP (129)Xe MR images display significant, directional heterogeneity, with increased signal intensity observed from the gravity-dependent portions of the lungs. CONCLUSIONS: The features observed in dissolved-phase (129)Xe MR images are consistent with gravity-dependent lung deformation, which produces increased ventilation, reduced alveolar size (i.e., higher surface-to-volume ratios), higher tissue densities, and increased perfusion in the dependent portions of the lungs. Thus, these results suggest that dissolved HP (129)Xe imaging reports on pulmonary function at a fundamental level.}, Language = {eng}, Doi = {10.1371/journal.pone.0012192}, Key = {fds268653} } @article{fds200612, Author = {SS Kaushik and ZI Cleveland and GP Cofer and G Metz and D Beaver and J Nouls, M Kraft and W Auffermann and J Wolber and HP McAdams and B Driehuys}, Title = {Diffusion-weighted hyperpolarized (129)Xe MRI in healthy volunteers and subjects with chronic obstructive pulmonary disease.}, Journal = {Magnetic resonance in medicine : official journal of the Society of Magnetic Resonance in Medicine / Society of Magnetic Resonance in Medicine}, Year = {2010}, Month = {December}, ISSN = {1522-2594}, url = {http://dx.doi.org/10.1002/mrm.22697}, Abstract = {Given its greater availability and lower cost, (129)Xe apparent diffusion coefficient (ADC) MRI offers an alternative to (3)He ADC MRI. To demonstrate the feasibility of hyperpolarized (129)Xe ADC MRI, we present results from healthy volunteers (HV), chronic obstructive pulmonary disease (COPD) subjects, and age-matched healthy controls (AMC). The mean parenchymal ADC was 0.036 ± 0.003 cm(2) sec(-1) for HV, 0.043 ± 0.006 cm(2) sec(-1) for AMC, and 0.056 ± 0.008 cm(2) sec(-1) for COPD subjects with emphysema. In healthy individuals, but not the COPD group, ADC decreased significantly in the anterior-posterior direction by ∼22% (P = 0.006, AMC; 0.0059, HV), likely because of gravity-induced tissue compression. The COPD group exhibited a significantly larger superior-inferior ADC reduction (∼28%) than the healthy groups (∼24%) (P = 0.00018, HV; P = 3.45 × 10(-5), AMC), consistent with smoking-related tissue destruction in the superior lung. Superior-inferior gradients in healthy subjects may result from regional differences in xenon concentration. ADC was significantly correlated with pulmonary function tests (forced expiratory volume in 1 sec, r = -0.77, P = 0.0002; forced expiratory volume in 1 sec/forced vital capacity, r = -0.77, P = 0.0002; diffusing capacity of carbon monoxide in the lung/alveolar volume (V(A)), r = -0.77, P = 0.0002). In healthy groups, ADC increased with age by 0.0002 cm(2) sec(-1) year(-1) (r = 0.56, P = 0.02). This study shows that (129)Xe ADC MRI is clinically feasible, sufficiently sensitive to distinguish HV from subjects with emphysema, and detects age- and posture-dependent changes. Magn Reson Med, 2010. © 2010 Wiley-Liss, Inc.}, Language = {ENG}, Doi = {10.1002/mrm.22697}, Key = {fds200612} } @article{fds268656, Author = {Kaushik, SS and Cleveland, ZI and Cofer, GP and Metz, G and Beaver, D and Nouls, J and Kraft, M and Auffermann, W and Wolber, J and McAdams, HP and Driehuys, B}, Title = {Diffusion-weighted hyperpolarized (129)Xe MRI in healthy volunteers and subjects with chronic obstructive pulmonary disease.}, Journal = {Magnetic Resonance in Medicine}, Volume = {65}, Number = {4}, Pages = {1154-65}, Year = {2010}, Month = {December}, ISSN = {1522-2594}, url = {http://www.ncbi.nlm.nih.gov/pubmed/21166014}, Keywords = {Administration, Inhalation • Adult • Aged • Contrast Media • Diffusion Magnetic Resonance Imaging • Female • Humans • Lung • Male • Middle Aged • Pulmonary Disease, Chronic Obstructive • Radiopharmaceuticals • Reference Values • Reproducibility of Results • Sensitivity and Specificity • Xenon Isotopes • administration & dosage • diagnosis* • diagnostic use* • methods* • pathology}, Abstract = {Given its greater availability and lower cost, (129)Xe apparent diffusion coefficient (ADC) MRI offers an alternative to (3)He ADC MRI. To demonstrate the feasibility of hyperpolarized (129)Xe ADC MRI, we present results from healthy volunteers (HV), chronic obstructive pulmonary disease (COPD) subjects, and age-matched healthy controls (AMC). The mean parenchymal ADC was 0.036 ± 0.003 cm(2) sec(-1) for HV, 0.043 ± 0.006 cm(2) sec(-1) for AMC, and 0.056 ± 0.008 cm(2) sec(-1) for COPD subjects with emphysema. In healthy individuals, but not the COPD group, ADC decreased significantly in the anterior-posterior direction by ∼22% (P = 0.006, AMC; 0.0059, HV), likely because of gravity-induced tissue compression. The COPD group exhibited a significantly larger superior-inferior ADC reduction (∼28%) than the healthy groups (∼24%) (P = 0.00018, HV; P = 3.45 × 10(-5), AMC), consistent with smoking-related tissue destruction in the superior lung. Superior-inferior gradients in healthy subjects may result from regional differences in xenon concentration. ADC was significantly correlated with pulmonary function tests (forced expiratory volume in 1 sec, r = -0.77, P = 0.0002; forced expiratory volume in 1 sec/forced vital capacity, r = -0.77, P = 0.0002; diffusing capacity of carbon monoxide in the lung/alveolar volume (V(A)), r = -0.77, P = 0.0002). In healthy groups, ADC increased with age by 0.0002 cm(2) sec(-1) year(-1) (r = 0.56, P = 0.02). This study shows that (129)Xe ADC MRI is clinically feasible, sufficiently sensitive to distinguish HV from subjects with emphysema, and detects age- and posture-dependent changes. Magn Reson Med, 2010. © 2010 Wiley-Liss, Inc.}, Language = {eng}, Doi = {10.1002/mrm.22697}, Key = {fds268656} } @article{fds268660, Author = {Zheng, W and Cleveland, ZI and Möller, HE and Driehuys, B}, Title = {Gradient-induced longitudinal relaxation of hyperpolarized noble gases in the fringe fields of superconducting magnets used for magnetic resonance.}, Journal = {Journal of Magnetic Resonance}, Volume = {208}, Number = {2}, Pages = {284-290}, Year = {2011}, Month = {February}, ISSN = {1096-0856}, url = {http://www.ncbi.nlm.nih.gov/pubmed/21134771}, Keywords = {Algorithms • Electromagnetic Fields • Helium • Magnetic Resonance Spectroscopy • Magnetics • Models, Theoretical • Noble Gases • chemistry • chemistry* • methods*}, Abstract = {When hyperpolarized noble gases are brought into the bore of a superconducting magnet for magnetic resonance imaging (MRI) or spectroscopy studies, the gases must pass through substantial field gradients, which can cause rapid longitudinal relaxation. In this communication, we present a means of calculating this spatially dependent relaxation rate in the fringe field of typical magnets. We then compare these predictions to experimental measurements of (3)He relaxation at various positions near a medium-bore 2-T small animal MRI system. The calculated and measured relaxation rates on the central axis of the magnet agree well and show a maximum (3)He relaxation rate of 3.83×10(-3) s(-1) (T(1)=4.4 min) at a distance of 47 cm from the magnet isocenter. We also show that if this magnet were self-shielded, its minimum T(1) would drop to 1.2 min. In contrast, a typical self-shielded 1.5-T clinical MRI scanner will induce a minimum on-axis T(1) of 12 min. Additionally, we show that the cylindrically symmetric fields of these magnets enable gradient-induced relaxation to be calculated using only knowledge of the on-axis longitudinal field, which can either be measured directly or calculated from a simple field model. Thus, while most MRI magnets employ complex and proprietary current configurations, we show that their fringe fields and the resulting gradient-induced relaxation are well approximated by simple solenoid models. Finally, our modeling also demonstrates that relaxation rates can increase by nearly an order of magnitude at radial distances equivalent to the solenoid radius.}, Language = {eng}, Doi = {10.1016/j.jmr.2010.11.006}, Key = {fds268660} } @article{fds268659, Author = {Nouls, J and Fanarjian, M and Hedlund, L and Driehuys, B}, Title = {A Constant-Volume Ventilator and Gas Recapture System for Hyperpolarized Gas MRI of Mouse and Rat Lungs.}, Journal = {Concepts in Magnetic Resonance Part B}, Volume = {39B}, Number = {2}, Pages = {78-88}, Year = {2011}, Month = {April}, ISSN = {1552-5031}, url = {http://www.ncbi.nlm.nih.gov/pubmed/21625347}, Language = {ENG}, Doi = {10.1002/cmr.b.20192}, Key = {fds268659} } @article{fds289610, Author = {Kaushik, SS and Cleveland, ZI and Cofer, GP and Metz, G and Beaver, D and Nouls, J and Kraft, M and Auffermann, W and Wolber, J and McAdams, HP and Driehuys, B}, Title = {Diffusion-weighted hyperpolarized 129Xe MRI in healthy volunteers and subjects with chronic obstructive pulmonary disease.}, Journal = {Magnetic Resonance in Medicine}, Volume = {65}, Number = {4}, Pages = {1154-1165}, Year = {2011}, Month = {April}, url = {http://www.ncbi.nlm.nih.gov/pubmed/21413080}, Abstract = {Given its greater availability and lower cost, (129) Xe apparent diffusion coefficient (ADC) MRI offers an alternative to (3) He ADC MRI. To demonstrate the feasibility of hyperpolarized (129) Xe ADC MRI, we present results from healthy volunteers (HV), chronic obstructive pulmonary disease (COPD) subjects, and age-matched healthy controls (AMC). The mean parenchymal ADC was 0.036 ± 0.003 cm(2) sec(-1) for HV, 0.043 ± 0.006 cm(2) sec(-1) for AMC, and 0.056 ± 0.008 cm(2) sec(-1) for COPD subjects with emphysema. In healthy individuals, but not the COPD group, ADC decreased significantly in the anterior-posterior direction by ∼ 22% (P = 0.006, AMC; 0.0059, HV), likely because of gravity-induced tissue compression. The COPD group exhibited a significantly larger superior-inferior ADC reduction (∼ 28%) than the healthy groups (∼ 24%) (P = 0.00018, HV; P = 3.45 × 10(-5) , AMC), consistent with smoking-related tissue destruction in the superior lung. Superior-inferior gradients in healthy subjects may result from regional differences in xenon concentration. ADC was significantly correlated with pulmonary function tests (forced expiratory volume in 1 sec, r = -0.77, P = 0.0002; forced expiratory volume in 1 sec/forced vital capacity, r = -0.77, P = 0.0002; diffusing capacity of carbon monoxide in the lung/alveolar volume (V(A) ), r = -0.77, P = 0.0002). In healthy groups, ADC increased with age by 0.0002 cm(2) sec(-1) year(-1) (r = 0.56, P = 0.02). This study shows that (129) Xe ADC MRI is clinically feasible, sufficiently sensitive to distinguish HV from subjects with emphysema, and detects age- and posture-dependent changes.}, Doi = {10.1002/mrm.22697}, Key = {fds289610} } @article{fds268657, Author = {Thomas, AC and Nouls, JC and Driehuys, B and Voltz, JW and Fubara, B and Foley, J and Bradbury, JA and Zeldin, DC}, Title = {Ventilation defects observed with hyperpolarized 3He magnetic resonance imaging in a mouse model of acute lung injury.}, Journal = {American journal of respiratory cell and molecular biology}, Volume = {44}, Number = {5}, Pages = {648-654}, Year = {2011}, Month = {May}, ISSN = {1535-4989}, url = {http://www.ncbi.nlm.nih.gov/pubmed/20595465}, Keywords = {Acute Lung Injury • Animals • Chemokine CCL2 • Chemokine CCL3 • Chemokine CXCL2 • Escherichia coli • Helium • Inflammation • Interleukin-1beta • Interleukin-6 • Lipopolysaccharides • Lung • Lung Diseases • Magnetic Resonance Imaging • Mice • Mice, Inbred C57BL • Positron-Emission Tomography • Tomography, X-Ray Computed • Total Lung Capacity • Tumor Necrosis Factor-alpha • diagnostic use • immunology • metabolism • metabolism* • methods • methods* • pharmacology}, Abstract = {Regions of diminished ventilation are often evident during functional pulmonary imaging studies, including hyperpolarized gas magnetic resonance imaging (MRI), positron emission tomography, and computed tomography (CT). The objective of this study was to characterize the hypointense regions observed via (3)He MRI in a murine model of acute lung injury. LPS at doses ranging from 15-50 μg was intratracheally administered to C57BL/6 mice under anesthesia. Four hours after exposure to either LPS or saline vehicle, mice were imaged via hyperpolarized (3)He MRI. All images were evaluated to identify regions of hypointense signals. Lungs were then characterized by conventional histology, or used to obtain tissue samples from regions of normal and hypointense (3)He signals and analyzed for cytokine content. The characterization of (3)He MRI images identified three distinct types of hypointense patterns: persistent defects, atelectatic defects, and dorsal lucencies. Persistent defects were associated with the administration of LPS. The number of persistent defects depended on the dose of LPS, with a significant increase in mean number of defects in 30-50-μg LPS-dosed mice versus saline-treated control mice. Atelectatic defects predominated in LPS-dosed mice under conditions of low-volume ventilation, and could be reversed with deep inspiration. Dorsal lucencies were present in nearly all mice studied, regardless of the experimental conditions, including control animals that did not receive LPS. A comparison of (3)He MRI with histopathology did not identify tissue abnormalities in regions of low (3)He signal, with the exception of a single region of atelectasis in one mouse. Furthermore, no statistically significant differences were evident in concentrations of IL-1β, IL-6, macrophage inflammatory protein (MIP)-1α, MIP-2, chemokine (C-X-C motif) ligand 1 (KC), TNFα, and monocyte chemotactic protein (MCP)-1 between hypointense and normally ventilated lung regions in LPS-dosed mice. Thus, this study defines the anatomic, functional, and biochemical characteristics of ventilation defects associated with the administration of LPS in a murine model of acute lung injury.}, Language = {eng}, Doi = {10.1165/rcmb.2009-0287OC}, Key = {fds268657} } @article{fds268658, Author = {Möller, HE and Cleveland, ZI and Driehuys, B}, Title = {Relaxation of hyperpolarized 129Xe in a deflating polymer bag.}, Journal = {Journal of Magnetic Resonance}, Volume = {212}, Number = {1}, Pages = {109-115}, Year = {2011}, Month = {September}, ISSN = {1096-0856}, url = {http://www.ncbi.nlm.nih.gov/pubmed/21752680}, Keywords = {Algorithms • Animals • Electromagnetic Fields • Image Processing, Computer-Assisted • Magnetic Resonance Imaging • Mice • Polymers • Polyvinyls • Radio Waves • Respiratory Mechanics • Xenon • Xenon Isotopes • chemistry* • methods* • physiology}, Abstract = {In magnetic resonance imaging with hyperpolarized (HP) noble gases, data is often acquired during prolonged gas delivery from a storage reservoir. However, little is known about the extent to which relaxation within the reservoir will limit the useful acquisition time. For quantitative characterization, 129Xe relaxation was studied in a bag made of polyvinyl fluoride (Tedlar). Particular emphasis was on wall relaxation, as this mechanism is expected to dominate. The HP 129Xe magnetization dynamics in the deflating bag were accurately described by a model assuming dissolution of Xe in the polymer matrix and dipolar relaxation with neighboring nuclear spins. In particular, the wall relaxation rate changed linearly with the surface-to-volume ratio and exhibited a relaxivity of κ=0.392±0.008 cm/h, which is in reasonable agreement with κ=0.331±0.051 cm/h measured in a static Tedlar bag. Estimates for the bulk gas-phase 129Xe relaxation yielded T1bulk=2.55±0.22 h, which is dominated by intrinsic Xe-Xe relaxation, with small additional contributions from magnetic field inhomogeneities and oxygen-induced relaxation. Calculations based on these findings indicate that relaxation may limit HP 129Xe experiments when slow gas delivery rates are employed as, for example, in mouse imaging or vascular infusion experiments.}, Language = {eng}, Doi = {10.1016/j.jmr.2011.06.017}, Key = {fds268658} } @article{fds268649, Author = {Cleveland, ZI and Möller, HE and Hedlund, LW and Nouls, JC and Freeman, MS and Qi, Y and Driehuys, B}, Title = {In vivo MR imaging of pulmonary perfusion and gas exchange in rats via continuous extracorporeal infusion of hyperpolarized 129Xe.}, Journal = {PloS one}, Volume = {7}, Number = {2}, Pages = {e31306}, Year = {2012}, url = {http://www.ncbi.nlm.nih.gov/pubmed/22363613}, Abstract = {BACKGROUND: Hyperpolarized (HP) (129)Xe magnetic resonance imaging (MRI) permits high resolution, regional visualization of pulmonary ventilation. Additionally, its reasonably high solubility (>10%) and large chemical shift range (>200 ppm) in tissues allow HP (129)Xe to serve as a regional probe of pulmonary perfusion and gas transport, when introduced directly into the vasculature. In earlier work, vascular delivery was accomplished in rats by first dissolving HP (129)Xe in a biologically compatible carrier solution, injecting the solution into the vasculature, and then detecting HP (129)Xe as it emerged into the alveolar airspaces. Although easily implemented, this approach was constrained by the tolerable injection volume and the duration of the HP (129)Xe signal. METHODS AND PRINCIPAL FINDINGS: Here, we overcome the volume and temporal constraints imposed by injection, by using hydrophobic, microporous, gas-exchange membranes to directly and continuously infuse (129)Xe into the arterial blood of live rats with an extracorporeal (EC) circuit. The resulting gas-phase (129)Xe signal is sufficient to generate diffusive gas exchange- and pulmonary perfusion-dependent, 3D MR images with a nominal resolution of 2×2×2 mm(3). We also show that the (129)Xe signal dynamics during EC infusion are well described by an analytical model that incorporates both mass transport into the blood and longitudinal relaxation. CONCLUSIONS: Extracorporeal infusion of HP (129)Xe enables rapid, 3D MR imaging of rat lungs and, when combined with ventilation imaging, will permit spatially resolved studies of the ventilation-perfusion ratio in small animals. Moreover, EC infusion should allow (129)Xe to be delivered elsewhere in the body and make possible functional and molecular imaging approaches that are currently not feasible using inhaled HP (129)Xe.}, Doi = {10.1371/journal.pone.0031306}, Key = {fds268649} } @article{fds268651, Author = {Driehuys, B and Nouls, J and Badea, A and Bucholz, E and Ghaghada, K and Petiet, A and Hedlund, LW}, Title = {Small animal imaging with magnetic resonance microscopy}, Journal = {ILAR Journal}, Volume = {53}, Number = {1}, Pages = {35-53}, Year = {2012}, ISSN = {1084-2020}, Abstract = {Small animal magnetic resonance microscopy (MRM) has evolved significantly from testing the boundaries of imaging physics to its expanding use today as a tool in noninvasive biomedical investigations. MRM now increasingly provides functional information about living animals, with images of the beating heart, breathing lung, and functioning brain. Unlike clinical MRI, where the focus is on diagnosis, MRM is used to reveal fundamental biology or to noninva-sively measure subtle changes in the structure or function of organs during disease progression or in response to experimental therapies. High-resolution anatomical imaging reveals increasingly exquisite detail in healthy animals and subtle architectural aberrations that occur in genetically altered models. Resolution of 100 μm in all dimensions is now routinely attained in living animals, and (10 (μm)3 is feasible in fixed specimens. Such images almost rival conventional histology while allowing the object to be viewed interactively in any plane. In this review we describe the state of the art in MRM for scientists who may be unfamiliar with this modality but who want to apply its capabilities to their research. We include a brief review of MR concepts and methods of animal handling and support, before covering a range of MRM applications-including the heart, lung, and brain-and the emerging field of MR histology. The ability of MRM to provide a detailed functional and anatomical picture in rats and mice, and to track this picture over time, makes it a promising platform with broad applications in biomedical research.}, Key = {fds268651} } @article{fds268654, Author = {Driehuys, B and Martinez-Jimenez, S and Cleveland, ZI and Metz, GM and Beaver, DM and Nouls, JC and Kaushik, SS and Firszt, R and Willis, C and Kelly, KT and Wolber, J and Kraft, M and McAdams, HP}, Title = {Chronic obstructive pulmonary disease: safety and tolerability of hyperpolarized 129Xe MR imaging in healthy volunteers and patients.}, Journal = {Radiology}, Volume = {262}, Number = {1}, Pages = {279-289}, Year = {2012}, Month = {January}, ISSN = {1527-1315}, url = {http://www.ncbi.nlm.nih.gov/pubmed/22056683}, Keywords = {Adult • Analysis of Variance • Case-Control Studies • Chi-Square Distribution • Electrocardiography • Female • Humans • Logistic Models • Magnetic Resonance Imaging • Male • Middle Aged • Prospective Studies • Pulmonary Disease, Chronic Obstructive • Xenon Isotopes • diagnosis* • diagnostic use • methods*}, Abstract = {PURPOSE: To evaluate the safety and tolerability of inhaling multiple 1-L volumes of undiluted hyperpolarized xenon 129 ((129)Xe) followed by up to a 16-second breath hold and magnetic resonance (MR) imaging. MATERIALS AND METHODS: This study was approved by the institutional review board and was HIPAA compliant. Written informed consent was obtained. Forty-four subjects (19 men, 25 women; mean age, 46.1 years ± 18.8 [standard deviation]) were enrolled, consisting of 24 healthy volunteers, 10 patients with chronic obstructive pulmonary disease (COPD), and 10 age-matched control subjects. All subjects received three or four 1-L volumes of undiluted hyperpolarized (129)Xe, followed by breath-hold MR imaging. Oxygen saturation, heart rate and rhythm, and blood pressure were continuously monitored. These parameters, along with respiratory rate and subjective symptoms, were assessed after each dose. Subjects' serum biochemistry and hematology were recorded at screening and at 24-hour follow-up. A 12-lead electrocardiogram (ECG) was obtained at these times and also within 2 hours prior to and 1 hour after (129)Xe MR imaging. Xenon-related symptoms were evaluated for relationship to subject group by using a χ(2) test and to subject age by using logistic regression. Changes in vital signs were tested for significance across subject group and time by using a repeated-measures multivariate analysis of variance test. RESULTS: The 44 subjects tolerated all xenon inhalations, no subjects withdrew, and no serious adverse events occurred. No significant changes in vital signs (P > .27) were observed, and no subjects exhibited changes in laboratory test or ECG results at follow-up that were deemed clinically important or required intervention. Most subjects (91%) did experience transient xenon-related symptoms, most commonly dizziness (59%), paresthesia (34%), euphoria (30%), and hypoesthesia (30%). All symptoms resolved without clinical intervention in 1.6 minutes ± 0.9. CONCLUSION: Inhalation of hyperpolarized (129)Xe is well tolerated in healthy subjects and in those with mild or moderate COPD. Subjects do experience mild, transient, xenon-related symptoms, consistent with its known anesthetic properties.}, Language = {eng}, Doi = {10.1148/radiol.11102172}, Key = {fds268654} } @article{fds325125, Author = {Cleveland, ZI and Freeman, M and Qi, Y and Driehuys, B}, Title = {Probing Diffusive Gas Uptake In Mice Using Hyperpolarized 129xe Magnetic Resonance Spectroscopy And Imaging}, Journal = {American journal of respiratory and critical care medicine}, Volume = {187}, Year = {2013}, Key = {fds325125} } @article{fds325126, Author = {Virgincar, RS and Nouls, J and He, M and Kaushik, SS and Potts, E and Foster, WM and Slipetz, DM and Hedlund, L and Driehuys, B}, Title = {Quantitative Analysis Of 3he And 1h Mr Images Of Regional Pulmonary Injury In House-Dust-Mite Allergic Mice}, Journal = {American journal of respiratory and critical care medicine}, Volume = {187}, Year = {2013}, Key = {fds325126} } @article{fds325127, Author = {Kaushik, SS and Liljeroth, M and Virgincar, RS and Robertson, SH and Davies, J and Stiles, J and Kelly, KT and Foster, WM and Morrison, L and McAdams, HP and Driehuys, B}, Title = {Reproducibility Of Hyperpolarized 129xe Mri: Alveolar Capillary Gas-Transfer Spectroscopy And Imaging}, Journal = {American journal of respiratory and critical care medicine}, Volume = {187}, Year = {2013}, Key = {fds325127} } @article{fds268627, Author = {Virgincar, RS and Cleveland, ZI and Kaushik, SS and Freeman, MS and Nouls, J and Cofer, GP and Martinez-Jimenez, S and He, M and Kraft, M and Wolber, J and Mcadams, HP and Driehuys, B}, Title = {Quantitative analysis of hyperpolarized 129Xe ventilation imaging in healthy volunteers and subjects with chronic obstructive pulmonary disease}, Journal = {Nmr in Biomedicine}, Volume = {26}, Number = {4}, Pages = {424-435}, Year = {2013}, ISSN = {0952-3480}, url = {http://dx.doi.org/10.1002/nbm.2880}, Abstract = {In this study, hyperpolarized 129Xe MR ventilation and 1H anatomical images were obtained from three subject groups: young healthy volunteers (HVs), subjects with chronic obstructive pulmonary disease (COPD) and age-matched controls (AMCs). Ventilation images were quantified by two methods: an expert reader-based ventilation defect score percentage (VDS%) and a semi-automated segmentation-based ventilation defect percentage (VDP). Reader-based values were assigned by two experienced radiologists and resolved by consensus. In the semi-automated analysis, 1H anatomical images and 129Xe ventilation images were both segmented following registration to obtain the thoracic cavity volume and ventilated volume, respectively, which were then expressed as a ratio to obtain the VDP. Ventilation images were also characterized by generating signal intensity histograms from voxels within the thoracic cavity volume, and heterogeneity was analyzed using the coefficient of variation (CV). The reader-based VDS% correlated strongly with the semi-automatically generated VDP (r=0.97, p&lt;0.0001) and with CV (r=0.82, p&lt;0.0001). Both 129Xe ventilation defect scoring metrics readily separated the three groups from one another and correlated significantly with the forced expiratory volume in 1s (FEV1) (VDS%: r=-0.78, p=0.0002; VDP: r=-0.79, p=0.0003; CV: r=-0.66, p=0.0059) and other pulmonary function tests. In the healthy subject groups (HVs and AMCs), the prevalence of ventilation defects also increased with age (VDS%: r=0.61, p=0.0002; VDP: r=0.63, p=0.0002). Moreover, ventilation histograms and their associated CVs distinguished between subjects with COPD with similar ventilation defect scores, but visibly different ventilation patterns. Copyright © 2012 John Wiley &amp; Sons, Ltd.}, Doi = {10.1002/nbm.2880}, Key = {fds268627} } @article{fds323789, Author = {Cleveland, ZI and Qi, Y and Driehuys, B}, Title = {Detecting Impaired Gas Uptake In A Rat Model Of Pulmonary Fibrosis With 3d Hyperpolarized 129xe Mri}, Journal = {American journal of respiratory and critical care medicine}, Volume = {187}, Year = {2013}, Key = {fds323789} } @article{fds268648, Author = {Virgincar, RS and Cleveland, ZI and Kaushik, SS and Freeman, MS and Nouls, J and Cofer, GP and Martinez-Jimenez, S and He, M and Kraft, M and Wolber, J and McAdams, HP and Driehuys, B}, Title = {Quantitative analysis of hyperpolarized 129Xe ventilation imaging in healthy volunteers and subjects with chronic obstructive pulmonary disease.}, Journal = {Nmr in Biomedicine}, Volume = {26}, Number = {4}, Pages = {424-435}, Year = {2013}, Month = {April}, url = {http://www.ncbi.nlm.nih.gov/pubmed/23065808}, Abstract = {In this study, hyperpolarized (129) Xe MR ventilation and (1) H anatomical images were obtained from three subject groups: young healthy volunteers (HVs), subjects with chronic obstructive pulmonary disease (COPD) and age-matched controls (AMCs). Ventilation images were quantified by two methods: an expert reader-based ventilation defect score percentage (VDS%) and a semi-automated segmentation-based ventilation defect percentage (VDP). Reader-based values were assigned by two experienced radiologists and resolved by consensus. In the semi-automated analysis, (1) H anatomical images and (129) Xe ventilation images were both segmented following registration to obtain the thoracic cavity volume and ventilated volume, respectively, which were then expressed as a ratio to obtain the VDP. Ventilation images were also characterized by generating signal intensity histograms from voxels within the thoracic cavity volume, and heterogeneity was analyzed using the coefficient of variation (CV). The reader-based VDS% correlated strongly with the semi-automatically generated VDP (r = 0.97, p < 0.0001) and with CV (r = 0.82, p < 0.0001). Both (129) Xe ventilation defect scoring metrics readily separated the three groups from one another and correlated significantly with the forced expiratory volume in 1 s (FEV1 ) (VDS%: r = -0.78, p = 0.0002; VDP: r = -0.79, p = 0.0003; CV: r = -0.66, p = 0.0059) and other pulmonary function tests. In the healthy subject groups (HVs and AMCs), the prevalence of ventilation defects also increased with age (VDS%: r = 0.61, p = 0.0002; VDP: r = 0.63, p = 0.0002). Moreover, ventilation histograms and their associated CVs distinguished between subjects with COPD with similar ventilation defect scores, but visibly different ventilation patterns.}, Doi = {10.1002/nbm.2880}, Key = {fds268648} } @article{fds268626, Author = {Kaushik, SS and Freeman, MS and Cleveland, ZI and Davies, J and Stiles, J and Virgincar, RS and Robertson, SH and He, M and Kelly, KT and Foster, WM and McAdams, HP and Driehuys, B}, Title = {Probing the regional distribution of pulmonary gas exchange through single-breath gas- and dissolved-phase 129Xe MR imaging.}, Journal = {Journal of applied physiology (Bethesda, Md. : 1985)}, Volume = {115}, Number = {6}, Pages = {850-860}, Year = {2013}, Month = {September}, url = {http://www.ncbi.nlm.nih.gov/pubmed/23845983}, Abstract = {Although some central aspects of pulmonary function (ventilation and perfusion) are known to be heterogeneous, the distribution of diffusive gas exchange remains poorly characterized. A solution is offered by hyperpolarized 129Xe magnetic resonance (MR) imaging, because this gas can be separately detected in the lung's air spaces and dissolved in its tissues. Early dissolved-phase 129Xe images exhibited intensity gradients that favored the dependent lung. To quantitatively corroborate this finding, we developed an interleaved, three-dimensional radial sequence to image the gaseous and dissolved 129Xe distributions in the same breath. These images were normalized and divided to calculate "129Xe gas-transfer" maps. We hypothesized that, for healthy volunteers, 129Xe gas-transfer maps would retain the previously observed posture-dependent gradients. This was tested in nine subjects: when the subjects were supine, 129Xe gas transfer exhibited a posterior-anterior gradient of -2.00 ± 0.74%/cm; when the subjects were prone, the gradient reversed to 1.94 ± 1.14%/cm (P < 0.001). The 129Xe gas-transfer maps also exhibited significant heterogeneity, as measured by the coefficient of variation, that correlated with subject total lung capacity (r = 0.77, P = 0.015). Gas-transfer intensity varied nonmonotonically with slice position and increased in slices proximal to the main pulmonary arteries. Despite substantial heterogeneity, the mean gas transfer for all subjects was 1.00 ± 0.01 while supine and 1.01 ± 0.01 while prone (P = 0.25), indicating good "matching" between gas- and dissolved-phase distributions. This study demonstrates that single-breath gas- and dissolved-phase 129Xe MR imaging yields 129Xe gas-transfer maps that are sensitive to altered gas exchange caused by differences in lung inflation and posture.}, Doi = {10.1152/japplphysiol.00092.2013}, Key = {fds268626} } @article{fds268619, Author = {Freeman, MS and Cleveland, ZI and Qi, Y and Driehuys, B}, Title = {Enabling hyperpolarized 129Xe MR spectroscopy and imaging of pulmonary gas transfer to the red blood cells in transgenic mice expressing human hemoglobin}, Journal = {Magnetic Resonance in Medicine}, Volume = {70}, Number = {5}, Pages = {1192-1199}, Year = {2013}, Month = {November}, ISSN = {0740-3194}, url = {http://dx.doi.org/10.1002/mrm.24915}, Abstract = {Purpose Hyperpolarized (HP) 129 Xe gas in the alveoli can be detected separately from 129 Xe dissolved in pulmonary barrier tissues (blood plasma and parenchyma) and red blood cells (RBCs) of humans, allowing this isotope to probe impaired gas uptake. Unfortunately, mice, which are favored as lung disease models, do not display a unique RBC resonance, thus limiting the preclinical utility of 129 Xe MR. Here we overcome this limitation using a commercially available strain of transgenic mice that exclusively expresses human hemoglobin. Methods Dynamic HP 129 Xe MR spectroscopy, and three-dimensional radial MRI of gaseous and dissolved 129 Xe were performed in both wild-type (C57BL/6) and transgenic mice. Results Unlike wild-type animals, transgenic mice displayed two dissolved 129 Xe NMR peaks at 198 and 217 ppm, corresponding to 129 Xe dissolved in barrier tissues and RBCs, respectively. Moreover, signal from these resonances could be imaged separately, using a 1-point variant of the Dixon technique. Conclusion It is now possible to examine the dynamics and spatial distribution of pulmonary gas uptake by the RBCs of mice using HP 129 Xe MR spectroscopy and imaging. When combined with ventilation imaging, this ability will enable translational "mouse-to-human" studies of impaired gas exchange in a variety of pulmonary diseases. Magn Reson Med 70:1192-1199, 2013. © 2013 Wiley Periodicals, Inc. Copyright © 2013 Wiley Periodicals, Inc.}, Doi = {10.1002/mrm.24915}, Key = {fds268619} } @article{fds268625, Author = {Freeman, MS and Cleveland, ZI and Qi, Y and Driehuys, B}, Title = {Enabling hyperpolarized (129) Xe MR spectroscopy and imaging of pulmonary gas transfer to the red blood cells in transgenic mice expressing human hemoglobin.}, Journal = {Magnetic Resonance in Medicine}, Volume = {70}, Number = {5}, Pages = {1192-1199}, Year = {2013}, Month = {November}, url = {http://www.ncbi.nlm.nih.gov/pubmed/24006177}, Abstract = {PURPOSE: Hyperpolarized (HP) (129) Xe gas in the alveoli can be detected separately from (129) Xe dissolved in pulmonary barrier tissues (blood plasma and parenchyma) and red blood cells (RBCs) of humans, allowing this isotope to probe impaired gas uptake. Unfortunately, mice, which are favored as lung disease models, do not display a unique RBC resonance, thus limiting the preclinical utility of (129) Xe MR. Here we overcome this limitation using a commercially available strain of transgenic mice that exclusively expresses human hemoglobin. METHODS: Dynamic HP (129) Xe MR spectroscopy, and three-dimensional radial MRI of gaseous and dissolved (129) Xe were performed in both wild-type (C57BL/6) and transgenic mice. RESULTS: Unlike wild-type animals, transgenic mice displayed two dissolved (129) Xe NMR peaks at 198 and 217 ppm, corresponding to (129) Xe dissolved in barrier tissues and RBCs, respectively. Moreover, signal from these resonances could be imaged separately, using a 1-point variant of the Dixon technique. CONCLUSION: It is now possible to examine the dynamics and spatial distribution of pulmonary gas uptake by the RBCs of mice using HP (129) Xe MR spectroscopy and imaging. When combined with ventilation imaging, this ability will enable translational "mouse-to-human" studies of impaired gas exchange in a variety of pulmonary diseases.}, Doi = {10.1002/mrm.24915}, Key = {fds268625} } @article{fds323722, Author = {He, M and Heacock, T and Kaushik, SS and Robertson, SH and Freeman, MS and McAdams, HP and Beaver, D and Kraft, M and Driehuys, B}, Title = {Hyperpolarized 129xe Mri To Quantify Regional Ventilation Differences In Older Versus Younger Asthmatics}, Journal = {American journal of respiratory and critical care medicine}, Volume = {189}, Year = {2014}, Key = {fds323722} } @article{fds323723, Author = {Kaushik, SS and Heacock, T and Freeman, M and Kelly, KT and Rackley, CR and Stiles, J and Foster, WM and McAdams, HP and Driehuys, B}, Title = {Hyperpolarized 129xe Spectroscopy As A Biomarker For Gas-Transfer Impairment In Idiopathic Pulmonary Fibrosis}, Journal = {American journal of respiratory and critical care medicine}, Volume = {189}, Year = {2014}, Key = {fds323723} } @article{fds268616, Author = {Freeman, MS and Emami, K and Driehuys, B}, Title = {Characterizing and modeling the efficiency limits in large-scale production of hyperpolarized (129)Xe.}, Journal = {Physical Review A - Atomic, Molecular, and Optical Physics}, Volume = {90}, Number = {2}, Pages = {023406}, Year = {2014}, Month = {August}, ISSN = {1050-2947}, url = {http://dx.doi.org/10.1103/physreva.90.023406}, Abstract = {The ability to produce liter volumes of highly spin-polarized (129)Xe enables a wide range of investigations, most notably in the fields of materials science and biomedical MRI. However, for nearly all polarizers built to date, both peak (129)Xe polarization and the rate at which it is produced fall far below those predicted by the standard model of Rb metal vapor, spin-exchange optical pumping (SEOP). In this work, we comprehensively characterized a high-volume, flow-through (129)Xe polarizer using three different SEOP cells with internal volumes of 100, 200 and 300 cc and two types of optical sources: a broad-spectrum 111-W laser (FWHM = 1.92 nm) and a line-narrowed 71-W laser (FWHM = 0.39 nm). By measuring (129)Xe polarization as a function of gas flow rate, we extracted peak polarization and polarization production rate across a wide range of laser absorption levels. Peak polarization for all cells consistently remained a factor of 2-3 times lower than predicted at all absorption levels. Moreover, although production rates increased with laser absorption, they did so much more slowly than predicted by the standard theoretical model and basic spin exchange efficiency arguments. Underperformance was most notable in the smallest optical cells. We propose that all these systematic deviations from theory can be explained by invoking the presence of paramagnetic Rb clusters within the vapor. Cluster formation within saturated alkali vapors is well established and their interaction with resonant laser light was recently shown to create plasma-like conditions. Such cluster systems cause both Rb and (129)Xe depolarization, as well as excess photon scattering. These effects were incorporated into the SEOP model by assuming that clusters are activated in proportion to excited-state Rb number density and by further estimating physically reasonable values for the nanocluster-induced, velocity-averaged spin-destruction cross-section for Rb (<σcluster-Rbv> ≈4×10(-7) cm(3)s(-1)), (129)Xe relaxation cross-section (<σcluster-Xev> ≈ 4×10(-13) cm(3)s(-1)), and a non-wavelength-specific, photon-scattering cross-section (σcluster ≈ 1×10(-12) cm(2)). The resulting modified SEOP model now closely matches experimental observations.}, Doi = {10.1103/physreva.90.023406}, Key = {fds268616} } @article{fds268617, Author = {Kaushik, SS and Freeman, MS and Yoon, SW and Liljeroth, MG and Stiles, JV and Roos, JE and Foster, WM and Rackley, CR and McAdams, HP and Driehuys, B}, Title = {Measuring diffusion limitation with a perfusion-limited gas--hyperpolarized 129Xe gas-transfer spectroscopy in patients with idiopathic pulmonary fibrosis.}, Journal = {Journal of applied physiology (Bethesda, Md. : 1985)}, Volume = {117}, Number = {6}, Pages = {577-585}, Year = {2014}, Month = {September}, ISSN = {8750-7587}, url = {http://dx.doi.org/10.1152/japplphysiol.00326.2014}, Abstract = {Although xenon is classically taught to be a "perfusion-limited" gas, (129)Xe in its hyperpolarized (HP) form, when detected by magnetic resonance (MR), can probe diffusion limitation. Inhaled HP (129)Xe diffuses across the pulmonary blood-gas barrier, and, depending on its tissue environment, shifts its resonant frequency relative to the gas-phase reference (0 ppm) by 198 ppm in tissue/plasma barrier and 217 ppm in red blood cells (RBCs). In this work, we hypothesized that in patients with idiopathic pulmonary fibrosis (IPF), the ratio of (129)Xe spectroscopic signal in the RBCs vs. barrier would diminish as diffusion-limitation delayed replenishment of (129)Xe magnetization in RBCs. To test this hypothesis, (129)Xe spectra were acquired in 6 IPF subjects as well as 11 healthy volunteers to establish a normal range. The RBC:barrier ratio was 0.55 ± 0.13 in healthy volunteers but was 3.3-fold lower in IPF subjects (0.16 ± 0.03, P = 0.0002). This was caused by a 52% reduction in the RBC signal (P = 0.02) and a 58% increase in the barrier signal (P = 0.01). Furthermore, the RBC:barrier ratio strongly correlated with lung diffusing capacity for carbon monoxide (DLCO) (r = 0.89, P < 0.0001). It exhibited a moderate interscan variability (8.25%), and in healthy volunteers it decreased with greater lung inflation (r = -0.78, P = 0.005). This spectroscopic technique provides a noninvasive, global probe of diffusion limitation and gas-transfer impairment and forms the basis for developing 3D MR imaging of gas exchange.}, Doi = {10.1152/japplphysiol.00326.2014}, Key = {fds268617} } @article{fds268615, Author = {He, M and Kaushik, SS and Robertson, SH and Freeman, MS and Virgincar, RS and McAdams, HP and Driehuys, B}, Title = {Extending semiautomatic ventilation defect analysis for hyperpolarized (129)Xe ventilation MRI.}, Journal = {Academic Radiology}, Volume = {21}, Number = {12}, Pages = {1530-1541}, Year = {2014}, Month = {December}, ISSN = {1076-6332}, url = {http://dx.doi.org/10.1016/j.acra.2014.07.017}, Abstract = {Clinical deployment of hyperpolarized (129)Xe magnetic resonance imaging requires accurate quantification and visualization of the ventilation defect percentage (VDP). Here, we improve the robustness of our previous semiautomated analysis method to reduce operator dependence, correct for B1 inhomogeneity and vascular structures, and extend the analysis to display multiple intensity clusters.Two segmentation methods were compared-a seeded region-growing method, previously validated by expert reader scoring, and a new linear-binning method that corrects the effects of bias field and vascular structures. The new method removes nearly all operator interventions by rescaling the (129)Xe magnetic resonance images to the 99th percentile of the cumulative distribution and applying fixed thresholds to classify (129)Xe voxels into four clusters: defect, low, medium, and high intensity. The methods were applied to 24 subjects including patients with chronic obstructive pulmonary disease (n = 8), age-matched controls (n = 8), and healthy normal subjects (n = 8).Linear-binning enabled a faster and more reproducible workflow and permitted analysis of an additional 0.25 ± 0.18 L of lung volume by accounting for vasculature. Like region-growing, linear-binning VDP correlated strongly with reader scoring (R(2) = 0.93, P < .0001), but with less systematic bias. Moreover, linear-binning maps clearly depict regions of low and high intensity that may prove useful for phenotyping subjects with chronic obstructive pulmonary disease.Corrected linear-binning provides a robust means to quantify (129)Xe ventilation images yielding VDP values that are indistinguishable from expert reader scores, while exploiting the entire dynamic range to depict multiple image clusters.}, Doi = {10.1016/j.acra.2014.07.017}, Key = {fds268615} } @article{fds268618, Author = {Cleveland, ZI and Virgincar, RS and Qi, Y and Robertson, SH and Degan, S and Driehuys, B}, Title = {3D MRI of impaired hyperpolarized 129Xe uptake in a rat model of pulmonary fibrosis.}, Journal = {Nmr in Biomedicine}, Volume = {27}, Number = {12}, Pages = {1502-1514}, Year = {2014}, Month = {December}, ISSN = {0952-3480}, url = {http://dx.doi.org/10.1002/nbm.3127}, Abstract = {A variety of pulmonary pathologies, in particular interstitial lung diseases, are characterized by thickening of the pulmonary blood-gas barrier, and this thickening results in reduced gas exchange. Such diffusive impairment is challenging to quantify spatially, because the distributions of the metabolically relevant gases (CO2 and O2) cannot be detected directly within the lungs. Hyperpolarized (HP) (129)Xe is a promising surrogate for these metabolic gases, because MR spectroscopy and imaging allow gaseous alveolar (129)Xe to be detected separately from (129)Xe dissolved in the red blood cells (RBCs) and the adjacent tissues, which comprise blood plasma and lung interstitium. Because (129)Xe reaches the RBCs by diffusing across the same barrier tissues (blood plasma and interstitium) as O2, barrier thickening will delay (129)Xe transit and, thus, reduce RBC-specific (129)Xe MR signal. Here we have exploited these properties to generate 3D, MR images of (129)Xe uptake by the RBCs in two groups of rats. In the experimental group, unilateral fibrotic injury was generated prior to imaging by instilling bleomycin into one lung. In the control group, a unilateral sham instillation of saline was performed. Uptake of (129)Xe by the RBCs, quantified as the fraction of RBC signal relative to total dissolved (129)Xe signal, was significantly reduced (P = 0.03) in the injured lungs of bleomycin-treated animals. In contrast, no significant difference (P = 0.56) was observed between the saline-treated and untreated lungs of control animals. Together, these results indicate that 3D MRI of HP (129)Xe dissolved in the pulmonary tissues can provide useful biomarkers of impaired diffusive gas exchange resulting from fibrotic thickening.}, Doi = {10.1002/nbm.3127}, Key = {fds268618} } @article{fds268613, Author = {Roos, JE and McAdams, HP and Kaushik, SS and Driehuys, B}, Title = {Hyperpolarized Gas MR Imaging: Technique and Applications.}, Journal = {Magnetic Resonance Imaging Clinics of North America}, Volume = {23}, Number = {2}, Pages = {217-229}, Year = {2015}, Month = {May}, ISSN = {1064-9689}, url = {http://dx.doi.org/10.1016/j.mric.2015.01.003}, Abstract = {Functional imaging offers information more sensitive to changes in lung structure and function. Hyperpolarized helium ((3)He) and xenon ((129)Xe) MR imaging of the lungs provides sensitive contrast mechanisms to probe changes in pulmonary ventilation, microstructure, and gas exchange. Gas imaging has shifted to the use of (129)Xe. Xenon is well-tolerated. (129)Xe is soluble in pulmonary tissue, which allows exploring specific lung function characteristics involved in gas exchange and alveolar oxygenation. Hyperpolarized gases and (129)Xe in particular stand to be an excellent probe of pulmonary structure and function, and provide sensitive and noninvasive biomarkers for pulmonary diseases.}, Doi = {10.1016/j.mric.2015.01.003}, Key = {fds268613} } @article{fds300329, Author = {Robertson, SH and Virgincar, RS and He, M and Freeman, MS and Kaushik, SS and Driehuys, B}, Title = {Optimizing 3D noncartesian gridding reconstruction for hyperpolarized 129 Xe MRI-focus on preclinical applications}, Journal = {Concepts in Magnetic Resonance}, Volume = {44}, Number = {4}, Pages = {190-202}, Year = {2015}, Month = {July}, ISSN = {1546-6086}, url = {http://dx.doi.org/10.1002/cmr.a.21352}, Abstract = {© 2015 Wiley Periodicals, Inc. The goal of this work is to characterize and optimize gridding reconstruction of 3D radial hyperpolarized (HP) 129Xe MRI. In support of this objective, we developed a flexible, open source reconstruction software package in MATLAB to optimally reconstruct radially acquired, undersampled HP 129Xe MRI. Using this framework, we demonstrate the effects of 5 key reconstruction parameters: overgridding, gridding kernel function, kernel sharpness, kernel extent, and the density compensation algorithm. We further demonstrate how each parameter can be tuned to optimize a high-resolution 3D radially acquired HP 129Xe image of a ventilated mouse. Specifically, wrap-around artifact, caused by non-selective RF excitation of signal in the trachea, was eliminated by overgridding onto a finely spaced k-space grid; high-frequency aliasing was reduced using iterative density compensation; image SNR and sharpness were optimized by tuning kernel sharpness; and computational burden was minimized by defining an appropriate kernel extent. Compared to our previous reconstruction methods, this optimized method extended visualization from the 5th to 6th generation of mouse airway, while maintaining comparable SNR. Although optimized here for preclinical mouse MRI, this work suggests that 3D radial acquisition offers many broader advantages to undersampled HP gas MRI. Using the methods presented here, we maintained image quality across datasets acquired with various degrees of undersampling and differing SNR by adjusting only a single parameter. These methods are now available to optimize radially acquired hyperpolarized gas images in both the clinical and preclinical arena.}, Doi = {10.1002/cmr.a.21352}, Key = {fds300329} } @article{fds268612, Author = {He, M and Robertson, SH and Kaushik, SS and Freeman, MS and Virgincar, RS and Davies, J and Stiles, J and Foster, WM and McAdams, HP and Driehuys, B}, Title = {Dose and pulse sequence considerations for hyperpolarized (129)Xe ventilation MRI.}, Journal = {Magnetic Resonance Imaging}, Volume = {33}, Number = {7}, Pages = {877-885}, Year = {2015}, Month = {September}, ISSN = {0730-725X}, url = {http://dx.doi.org/10.1016/j.mri.2015.04.005}, Abstract = {The aim of this study was to evaluate the effect of hyperpolarized (129)Xe dose on image signal-to-noise ratio (SNR) and ventilation defect conspicuity on both multi-slice gradient echo and isotropic 3D-radially acquired ventilation MRI.Ten non-smoking older subjects (ages 60.8±7.9years) underwent hyperpolarized (HP) (129)Xe ventilation MRI using both GRE and 3D-radial acquisitions, each tested using a 71ml (high) and 24ml (low) dose equivalent (DE) of fully polarized, fully enriched (129)Xe. For all images SNR and ventilation defect percentage (VDP) were calculated.Normalized SNR (SNRn), obtained by dividing SNR by voxel volume and dose was higher for high-DE GRE acquisitions (SNRn=1.9±0.8ml(-2)) than low-DE GRE scans (SNRn=0.8±0.2ml(-2)). Radially acquired images exhibited a more consistent, albeit lower SNRn (High-DE: SNRn=0.5±0.1ml(-2), low-DE: SNRn=0.5±0.2ml(-2)). VDP was indistinguishable across all scans.These results suggest that images acquired using the high-DE GRE sequence provided the highest SNRn, which was in agreement with previous reports in the literature. 3D-radial images had lower SNRn, but have advantages for visual display, monitoring magnetization dynamics, and visualizing physiological gradients. By evaluating normalized SNR in the context of dose-equivalent formalism, it should be possible to predict (129)Xe dose requirements and quantify the benefits of more efficient transmit/receive coils, field strengths, and pulse sequences.}, Doi = {10.1016/j.mri.2015.04.005}, Key = {fds268612} } @article{fds323721, Author = {He, M and Robertson, SH and Wang, JM and Rackley, CR and McAdams, HP and Driehuys, B}, Title = {Differentiating Early Stage And Later Stage Ipf Using Hyperpolarized 129xe Ventilation Mri}, Journal = {American journal of respiratory and critical care medicine}, Volume = {193}, Year = {2016}, Key = {fds323721} } @article{fds323720, Author = {Wang, JM and Robertson, SH and He, M and Virgincar, RS and Schrank, GM and Smigla, R and O'Riordan, T and Sundy, J and Ebner, L and Rackley, CR and McAdams, HP and Driehuys, B}, Title = {Using Hyperpolarized 129xe Imaging To Quantify Apical Vs. Basal And Central Vs. Peripheral Gas Exchange Impairment In Idiopathic Pulmonary Fibrosis}, Journal = {American journal of respiratory and critical care medicine}, Volume = {193}, Year = {2016}, Key = {fds323720} } @article{fds323788, Author = {He, M and Robertson, SH and Wang, JM and Que, LG and Mahmood, K and Driehuys, B and Huang, Y-C}, Title = {Characterizing The Ventilation Distribution In Healthy Normal Subjects To Establish Robust Quantitative Analysis Of 129xe Mri}, Journal = {American journal of respiratory and critical care medicine}, Volume = {193}, Year = {2016}, Key = {fds323788} } @article{fds315945, Author = {Dahhan, T and Kaushik, SS and He, M and Mammarappallil, JG and Tapson, VF and McAdams, HP and Sporn, TA and Driehuys, B and Rajagopal, S}, Title = {Abnormalities in hyperpolarized (129)Xe magnetic resonance imaging and spectroscopy in two patients with pulmonary vascular disease.}, Journal = {Pulmonary Circulation}, Volume = {6}, Number = {1}, Pages = {126-131}, Year = {2016}, Month = {March}, ISSN = {2045-8932}, url = {http://dx.doi.org/10.1086/685110}, Abstract = {The diagnosis of pulmonary vascular disease (PVD) is usually based on hemodynamic and/or clinical criteria. Noninvasive imaging of the heart and proximal vasculature can also provide useful information. An alternate approach to such criteria in the diagnosis of PVD is to image the vascular abnormalities in the lungs themselves. Hyperpolarized (HP) (129)Xe magnetic resonance imaging (MRI) is a novel technique for assessing abnormalities in ventilation and gas exchange in the lungs. We applied this technique to two patients for whom there was clinical suspicion of PVD. Two patients who had significant hypoxemia and dyspnea with no significant abnormalities on computed tomography imaging or ventilation-perfusion scan and only mild or borderline pulmonary arterial hypertension at catheterization were evaluated. They underwent HP (129)Xe imaging and subsequently had tissue diagnosis obtained from lung pathology. In both patients, HP (129)Xe imaging demonstrated normal ventilation but markedly decreased gas transfer to red blood cells with focal defects on imaging, a pattern distinct from those previously described for idiopathic pulmonary fibrosis or obstructive lung disease. Pathology on both patients later demonstrated severe PVD. These findings suggest that HP (129)Xe MRI may be useful in the diagnosis of PVD and monitoring response to therapy. Further studies are required to determine its sensitivity and specificity in these settings.}, Doi = {10.1086/685110}, Key = {fds315945} } @article{fds268614, Author = {Kaushik, SS and Robertson, SH and Freeman, MS and He, M and Kelly, KT and Roos, JE and Rackley, CR and Foster, WM and McAdams, HP and Driehuys, B}, Title = {Single-breath clinical imaging of hyperpolarized (129)Xe in the airspaces, barrier, and red blood cells using an interleaved 3D radial 1-point Dixon acquisition.}, Journal = {Magnetic Resonance in Medicine}, Volume = {75}, Number = {4}, Pages = {1434-1443}, Year = {2016}, Month = {April}, ISSN = {0740-3194}, url = {http://dx.doi.org/10.1002/mrm.25675}, Abstract = {We sought to develop and test a clinically feasible 1-point Dixon, three-dimensional (3D) radial acquisition strategy to create isotropic 3D MR images of (129)Xe in the airspaces, barrier, and red blood cells (RBCs) in a single breath. The approach was evaluated in healthy volunteers and subjects with idiopathic pulmonary fibrosis (IPF).A calibration scan determined the echo time at which (129)Xe in RBCs and barrier were 90° out of phase. At this TE, interleaved dissolved and gas-phase images were acquired using a 3D radial acquisition and were reconstructed separately using the NUFFT algorithm. The dissolved-phase image was phase-shifted to cast RBC and barrier signal into the real and imaginary channels such that the image-derived RBC:barrier ratio matched that from spectroscopy. The RBC and barrier images were further corrected for regional field inhomogeneity using a phase map created from the gas-phase (129)Xe image.Healthy volunteers exhibited largely uniform (129)Xe-barrier and (129)Xe-RBC images. By contrast, (129)Xe-RBC images in IPF subjects exhibited significant signal voids. These voids correlated qualitatively with regions of fibrosis visible on CT.This study illustrates the feasibility of acquiring single-breath, 3D isotropic images of (129)Xe in the airspaces, barrier, and RBCs using a 1-point Dixon 3D radial acquisition.}, Doi = {10.1002/mrm.25675}, Key = {fds268614} } @article{fds323787, Author = {Subashi, E and Liu, Y and Robertson, S and Segars, P and Driehuys, B and Yin, F and Cai, J}, Title = {TH-EF-BRA-10: High Spatiotemporal Resolution Self-Sorted 4D MRI.}, Journal = {Medical physics}, Volume = {43}, Number = {6}, Pages = {3899}, Year = {2016}, Month = {June}, url = {http://dx.doi.org/10.1118/1.4958267}, Abstract = {To describe a novel method for self-sorted 4D-MRI and to characterize the output image quality as measured by signal-to-noise ratio (SNR), spatiotemporal resolution, and level of artifact.A three-dimensional radial sampling function with a quasi-random distribution of polar/azimuthal k-space angles was implemented in a standard pulse sequence. Acquisition time was approximately 2 minutes. The DC component of the k-space signal was used to estimate and sort the breathing cycle into ten respiratory phases. For a given respiratory phase, the k-space data were combined with the periphery of the k-space data from all phases and reconstructed with the re-gridding algorithm onto a 1283 matrix. The extent of data sharing was controlled by the average breathing curve. The sampling and reconstruction technique were tested and validated in simulation, dynamic phantom, animal, and human studies with varying breathing periods/amplitudes.The signal at the k-space center accurately measures respiratory motion over a large range of breathing periods (0.5-7.0 seconds) and amplitudes (5-30% of FOV). Sharing of high frequency k-space data driven by the average breathing curve improves spatial resolution and artifact level at a cost of an increase in noise floor. Although equal sharing of k-space data improves resolution and SNR, phases with large temporal changes accumulate considerable distortion artifacts. In the absence of view-sharing, no distortion artifacts are observed while spatial resolution is degraded.The use of a quasi-random sampling function and view-sharing driven by the average breathing curve provide a feasible method for self-sorted 4D MRI at reduced acquisition times. This approach allows for the extent of data sharing to be inversely-proportional to the average breathing motion hence improving resolution and decreasing artifact levels. NIH-1R21CA165384.}, Doi = {10.1118/1.4958267}, Key = {fds323787} } @article{fds320112, Author = {Robertson, SH and Virgincar, RS and Bier, EA and He, M and Schrank, GM and Smigla, RM and Rackley, C and McAdams, HP and Driehuys, B}, Title = {Uncovering a third dissolved-phase 129Xe resonance in the human lung: Quantifying spectroscopic features in healthy subjects and patients with idiopathic pulmonary fibrosis.}, Journal = {Magnetic Resonance in Medicine}, Year = {2016}, Month = {November}, url = {http://dx.doi.org/10.1002/mrm.26533}, Abstract = {The purpose of this work was to accurately characterize the spectral properties of hyperpolarized 129Xe in patients with idiopathic pulmonary fibrosis (IPF) compared to healthy volunteers.Subjects underwent hyperpolarized 129Xe breath-hold spectroscopy, during which 38 dissolved-phase free induction decays (FIDs) were acquired after reaching steady state (echo time/repetition time = 0.875/50 ms; bandwidth = 8.06 kHz; flip angle≈22 °). FIDs were averaged and then decomposed into multiple spectral components using time-domain curve fitting. The resulting amplitudes, frequencies, line widths, and starting phases of each component were compared among groups using a Mann-Whitney-Wilcoxon U test.Three dissolved-phase resonances, consisting of red blood cells (RBCs) and two barrier compartments, were consistently identified in all subjects. In subjects with IPF relative to healthy volunteers, the RBC frequency was 0.70 parts per million (ppm) more negative (P = 0.05), the chemical shift of barrier 2 was 0.6 ppm more negative (P = 0.009), the line widths of both barrier peaks were ∼2 ppm narrower (P < 0.001), and the starting phase of barrier 1 was 20.3 ° higher (P =  0.01). Moreover, the ratio RBC:barriers was reduced by 52.9% in IPF (P < 0.001).The accurate decomposition of 129Xe spectra not only has merit for developing a global metric of pulmonary function, but also provides necessary insights to optimize phase-sensitive methods for imaging 129Xe gas transfer. Magn Reson Med, 2016. © 2016 International Society for Magnetic Resonance in Medicine.}, Doi = {10.1002/mrm.26533}, Key = {fds320112} } @article{fds320111, Author = {He, M and Driehuys, B and Que, LG and Huang, Y-CT}, Title = {Using Hyperpolarized 129Xe MRI to Quantify the Pulmonary Ventilation Distribution.}, Journal = {Academic Radiology}, Volume = {23}, Number = {12}, Pages = {1521-1531}, Year = {2016}, Month = {December}, url = {http://dx.doi.org/10.1016/j.acra.2016.07.014}, Abstract = {Ventilation heterogeneity is impossible to detect with spirometry. Alternatively, pulmonary ventilation can be imaged three-dimensionally using inhaled 129Xe magnetic resonance imaging (MRI). To date, such images have been quantified primarily based on ventilation defects. Here, we introduce a robust means to transform 129Xe MRI scans such that the underlying ventilation distribution and its heterogeneity can be quantified.Quantitative 129Xe ventilation MRI was conducted in 12 younger (24.7 ± 5.2 years) and 10 older (62.2 ± 7.2 years) healthy individuals, as well as in 9 younger (25.9 ± 6.4 yrs) and 10 older (63.2 ± 6.1 years) asthmatics. The younger healthy population was used to establish a reference ventilation distribution and thresholds for six intensity bins. These bins were used to display and quantify the ventilation defect region (VDR), the low ventilation region (LVR), and the high ventilation region (HVR).The ventilation distribution in young subjects was roughly Gaussian with a mean and standard deviation of 0.52 ± 0.18, resulting in VDR = 2.1 ± 1.3%, LVR = 15.6 ± 5.4%, and HVR = 17.4 ± 3.1%. Older healthy volunteers exhibited a significantly right-skewed distribution (0.46 ± 0.20, P = 0.034), resulting in significantly increased VDR (7.0 ± 4.8%, P = 0.008) and LVR (24.5 ± 11.5%, P = 0.025). In the asthmatics, VDR and LVR increased in the older population, and HVR was significantly reduced (13.5 ± 4.6% vs 18.9 ± 4.5%, P = 0.009). Quantitative 129Xe MRI also revealed altered ventilation heterogeneity in response to albuterol in two asthmatics with normal spirometry.Quantitative 129Xe MRI provides a robust and objective means to display and quantify the pulmonary ventilation distribution, even in subjects who have airway function impairment not appreciated by spirometry.}, Doi = {10.1016/j.acra.2016.07.014}, Key = {fds320111} } @article{fds326797, Author = {He, M and Zha, W and Fain, SB and Driehuys, B}, Title = {Comparing Quantitative 129xe Ventilation Analysis Pipelines Between Mri Centers}, Journal = {American journal of respiratory and critical care medicine}, Volume = {195}, Year = {2017}, Key = {fds326797} } @article{fds326796, Author = {Nichols, C and House, J and Li, H and Brandenberger, C and Virgincar, R and Miller, L and Driehuys, B and Zeldin, D and London, S}, Title = {Htr4 Regulates Pulmonary Function Through Neural Innervation}, Journal = {American journal of respiratory and critical care medicine}, Volume = {195}, Year = {2017}, Key = {fds326796} } @article{fds320114, Author = {Ebner, L and Kammerman, J and Driehuys, B and Schiebler, ML and Cadman, RV and Fain, SB}, Title = {The role of hyperpolarized 129xenon in MR imaging of pulmonary function.}, Journal = {European Journal of Radiology}, Volume = {86}, Pages = {343-352}, Year = {2017}, Month = {January}, url = {http://dx.doi.org/10.1016/j.ejrad.2016.09.015}, Abstract = {In the last two decades, functional imaging of the lungs using hyperpolarized noble gases has entered the clinical stage. Both helium (3He) and xenon (129Xe) gas have been thoroughly investigated for their ability to assess both the global and regional patterns of lung ventilation. With advances in polarizer technology and the current transition towards the widely available 129Xe gas, this method is ready for translation to the clinic. Currently, hyperpolarized (HP) noble gas lung MRI is limited to selected academic institutions; yet, the promising results from initial clinical trials have drawn the attention of the pulmonary medicine community. HP 129Xe MRI provides not only 3-dimensional ventilation imaging, but also unique capabilities for probing regional lung physiology. In this review article, we aim to (1) provide a brief overview of current ventilation MR imaging techniques, (2) emphasize the role of HP 129Xe MRI within the array of different imaging strategies, (3) discuss the unique imaging possibilities with HP 129Xe MRI, and (4) propose clinical applications.}, Doi = {10.1016/j.ejrad.2016.09.015}, Key = {fds320114} } @article{fds321759, Author = {Driehuys, B}, Title = {Crossing the Chasm(s): Demonstrating the Clinical Value of Hyperpolarized Gas MRI.}, Journal = {Academic Radiology}, Volume = {24}, Number = {1}, Pages = {1-3}, Year = {2017}, Month = {January}, url = {http://dx.doi.org/10.1016/j.acra.2016.11.002}, Doi = {10.1016/j.acra.2016.11.002}, Key = {fds321759} } @article{fds320113, Author = {Ebner, L and He, M and Virgincar, RS and Heacock, T and Kaushik, SS and Freemann, MS and McAdams, HP and Kraft, M and Driehuys, B}, Title = {Hyperpolarized 129Xenon Magnetic Resonance Imaging to Quantify Regional Ventilation Differences in Mild to Moderate Asthma: A Prospective Comparison Between Semiautomated Ventilation Defect Percentage Calculation and Pulmonary Function Tests.}, Journal = {Investigative Radiology}, Volume = {52}, Number = {2}, Pages = {120-127}, Year = {2017}, Month = {February}, url = {http://dx.doi.org/10.1097/rli.0000000000000322}, Abstract = {The aim of this study was to investigate ventilation in mild to moderate asthmatic patients and age-matched controls using hyperpolarized (HP) Xenon magnetic resonance imaging (MRI) and correlate findings with pulmonary function tests (PFTs).This single-center, Health Insurance Portability and Accountability Act-compliant prospective study was approved by our institutional review board. Thirty subjects (10 young asthmatic patients, 26 ± 6 years; 3 males, 7 females; 10 older asthmatic patients, 64 ± 6 years; 3 males, 7 females; 10 healthy controls) were enrolled. After repeated PFTs 1 week apart, the subjects underwent 2 MRI scans within 10 minutes, inhaling 1-L volumes containing 0.5 to 1 L of Xe. Xe ventilation signal was quantified by linear binning, from which the ventilation defect percentage (VDP) was derived. Differences in VDP among subgroups and variability with age were evaluated using 1-tailed t tests. Correlation of VDP with PFTs was tested using Pearson correlation coefficient. Reproducibility of VDP was assessed using Bland-Altman plots, linear regression (R), intraclass correlation coefficient, and concordance correlation coefficient.Ventilation defect percentage was significantly higher in young asthmatic patients versus young healthy subjects (8.4% ± 3.2% vs 5.6% ± 1.7%, P = 0.031), but not in older asthmatic patients versus age-matched controls (16.8% ± 10.3% vs 11.6% ± 6.6%, P = 0.13). Ventilation defect percentage was found to increase significantly with age (healthy, P = 0.05; asthmatic patients, P = 0.033). Ventilation defect percentage was highly reproducible (R = 0.976; intraclass correlation coefficient, 0.977; concordance correlation coefficient, 0.976) and significantly correlated with FEV1% (r = -0.42, P = 0.025), FEF25%-75% (r = -0.45, P = 0.019), FEV1/FVC (r = -0.71, P < 0.0001), FeNO (r = 0.69, P < 0.0001), and RV/TLC (r = 0.51, P = 0.0067). Bland-Altman analysis showed a bias for VDP of -0.88 ± 1.52 (FEV1%, -0.33 ± 7.18).Xenon MRI is able to depict airway obstructions in mild to moderate asthma and significantly correlates with PFTs.}, Doi = {10.1097/rli.0000000000000322}, Key = {fds320113} } @article{fds315007, Author = {Virgincar, RS and Robertson, SH and Nouls, J and Degan, S and Schrank, GM and He, M and Driehuys, B}, Title = {Establishing an accurate gas phase reference frequency to quantify 129 Xe chemical shifts in vivo.}, Journal = {Magnetic Resonance in Medicine}, Volume = {77}, Number = {4}, Pages = {1438-1445}, Year = {2017}, Month = {April}, ISSN = {0740-3194}, url = {http://dx.doi.org/10.1002/mrm.26229}, Abstract = {129 Xe interacts with biological media to exhibit chemical shifts exceeding 200 ppm that report on physiology and pathology. Extracting this functional information requires shifts to be measured precisely. Historically, shifts have been reported relative to the gas-phase resonance originating from pulmonary airspaces. However, this frequency is not fixed-it is affected by bulk magnetic susceptibility, as well as Xe-N2 , Xe-Xe, and Xe-O2 interactions. In this study, we addressed this by introducing a robust method to determine the 0 ppm 129 Xe reference from in vivo data.Respiratory-gated hyperpolarized 129 Xe spectra from the gas- and dissolved-phases were acquired in four mice at 2T from multiple axial slices within the thoracic cavity. Complex spectra were then fitted in the time domain to identify peaks.Gas-phase 129 Xe exhibited two distinct resonances corresponding to 129 Xe in conducting airways (varying from -0.6 ± 0.2 to 1.3 ± 0.3 ppm) and alveoli (relatively stable, at -2.2 ± 0.1 ppm). Dissolved-phase 129 Xe exhibited five reproducible resonances in the thorax at 198.4 ± 0.4, 195.5 ± 0.4, 193.9 ± 0.2, 191.3 ± 0.2, and 190.7 ± 0.3 ppm.The alveolar 129 Xe resonance exhibits a stable frequency across all mice. Therefore, it can provide a reliable in vivo reference frequency by which to characterize other spectroscopic shifts. Magn Reson Med 77:1438-1445, 2017. © 2016 International Society for Magnetic Resonance in Medicine.}, Doi = {10.1002/mrm.26229}, Key = {fds315007} } @article{fds325124, Author = {House, JS and Nichols, CE and Li, H and Brandenberger, C and Virgincar, RS and DeGraff, LM and Driehuys, B and Zeldin, DC and London, SJ}, Title = {Vagal innervation is required for pulmonary function phenotype in Htr4-/- mice.}, Journal = {American journal of physiology. Lung cellular and molecular physiology}, Volume = {312}, Number = {4}, Pages = {L520-L530}, Year = {2017}, Month = {April}, url = {http://dx.doi.org/10.1152/ajplung.00495.2016}, Abstract = {Human genome-wide association studies have identified over 50 loci associated with pulmonary function and related phenotypes, yet follow-up studies to determine causal genes or variants are rare. Single nucleotide polymorphisms in serotonin receptor 4 (HTR4) are associated with human pulmonary function in genome-wide association studies and follow-up animal work has demonstrated that Htr4 is causally associated with pulmonary function in mice, although the precise mechanisms were not identified. We sought to elucidate the role of neural innervation and pulmonary architecture in the lung phenotype of Htr4-/- animals. We report here that the Htr4-/- phenotype in mouse is dependent on vagal innervation to the lung. Both ex vivo tracheal ring reactivity and in vivo flexiVent pulmonary functional analyses demonstrate that vagotomy abrogates the Htr4-/- airway hyperresponsiveness phenotype. Hyperpolarized 3He gas magnetic resonance imaging and stereological assessment of wild-type and Htr4-/- mice reveal no observable differences in lung volume, inflation characteristics, or pulmonary microarchitecture. Finally, control of breathing experiments reveal substantive differences in baseline breathing characteristics between mice with/without functional HTR4 in breathing frequency, relaxation time, flow rate, minute volume, time of inspiration and expiration and breathing pauses. These results suggest that HTR4's role in pulmonary function likely relates to neural innervation and control of breathing.}, Doi = {10.1152/ajplung.00495.2016}, Key = {fds325124} } @article{fds326237, Author = {Wang, Z and Robertson, SH and Wang, J and He, M and Virgincar, RS and Schrank, GM and Bier, EA and Rajagopal, S and Huang, YC and O'Riordan, TG and Rackley, CR and McAdams, HP and Driehuys, B}, Title = {Quantitative analysis of hyperpolarized 129 Xe gas transfer MRI.}, Journal = {Medical physics}, Volume = {44}, Number = {6}, Pages = {2415-2428}, Year = {2017}, Month = {June}, url = {http://dx.doi.org/10.1002/mp.12264}, Abstract = {Hyperpolarized 129 Xe magnetic resonance imaging (MRI) using Dixon-based decomposition enables single-breath imaging of 129 Xe in the airspaces, interstitial barrier tissues, and red blood cells (RBCs). However, methods to quantitatively visualize information from these images of pulmonary gas transfer are lacking. Here, we introduce a novel method to transform these data into quantitative maps of pulmonary ventilation, and 129 Xe gas transfer to barrier and RBC compartments.A total of 13 healthy subjects and 12 idiopathic pulmonary fibrosis (IPF) subjects underwent thoracic 1 H MRI and hyperpolarized 129 Xe MRI with one-point Dixon decomposition to obtain images of 129 Xe in airspaces, barrier and red blood cells (RBCs). 129 Xe images were processed into quantitative binning maps of all three compartments using thresholds based on the mean and standard deviations of distributions derived from the healthy reference cohort. Binning maps were analyzed to derive quantitative measures of ventilation, barrier uptake, and RBC transfer. This method was also used to illustrate different ventilation and gas transfer patterns in a patient with emphysema and one with pulmonary arterial hypertension (PAH).In the healthy reference cohort, the mean normalized signals were 0.51 ± 0.19 for ventilation, 4.9 ± 1.5 x 10-3 for barrier uptake and 2.6 ± 1.0 × 10-3 for RBC (transfer). In IPF patients, ventilation was similarly homogenous to healthy subjects, although shifted toward slightly lower values (0.43 ± 0.19). However, mean barrier uptake in IPF patients was nearly 2× higher than in healthy subjects, with 47% of voxels classified as high, compared to 3% in healthy controls. Moreover, in IPF, RBC transfer was reduced, mainly in the basal lung with 41% of voxels classified as low. In healthy volunteers, only 15% of RBC transfer was classified as low and these voxels were typically in the anterior, gravitationally nondependent lung.This study demonstrates a straightforward means to generate semiquantitative binning maps depicting 129 Xe ventilation and gas transfer to barrier and RBC compartments. These initial results suggest that the method could be valuable for characterizing both normal physiology and pathophysiology associated with a wide range of pulmonary disorders.}, Doi = {10.1002/mp.12264}, Key = {fds326237} } @article{fds326238, Author = {Mahmood, K and Ebner, L and He, M and Robertson, SH and Wang, Z and McAdams, HP and Wahidi, MM and Shofer, SL and Huang, YT and Driehuys, B}, Title = {Novel Magnetic Resonance Imaging for Assessment of Bronchial Stenosis in Lung Transplant Recipients.}, Journal = {American Journal of Transplantation}, Volume = {17}, Number = {7}, Pages = {1895-1904}, Year = {2017}, Month = {July}, url = {http://dx.doi.org/10.1111/ajt.14287}, Abstract = {Bronchial stenosis in lung transplant recipients is a common disorder that adversely affects clinical outcomes. It is evaluated by spirometry, CT scanning, and bronchoscopy with significant limitations. We hypothesize that MRI using both ultrashort echo time (UTE) scans and hyperpolarized (HP) 129 Xe gas can offer structural and functional assessment of bronchial stenosis seen after lung transplantation. Six patients with lung transplantation-related bronchial stenosis underwent HP 129 Xe MRI and UTE MRI in the same session. Three patients subsequently underwent airway stent placement and had repeated MRI at 4-week follow-up. HP 129 Xe MRI depicted decreased ventilation distal to the stenotic airway. After airway stent placement, MRI showed that low-ventilation regions had decreased (35% vs. 27.6%, p = 0.006) and normal-ventilation regions had increased (17.9% vs. 27.6%, p = 0.04) in the stented lung. Improved gas transfer was also seen on 129 Xe MRI. There was a good correlation between UTE MRI and independent bronchoscopic airway diameter assessment (Pearson correlation coefficient = 0.92). This pilot study shows that UTE and HP 129 Xe MRI are feasible in patients with bronchial stenosis related to lung transplantation and may provide structural and functional airway assessment to guide treatment. These conclusions need to be confirmed with larger studies.}, Doi = {10.1111/ajt.14287}, Key = {fds326238} } @article{fds327669, Author = {Flower, C and Freeman, MS and Plue, M and Driehuys, B}, Title = {Electron microscopic observations of Rb particles and pitting in 129Xe spin-exchange optical pumping cells.}, Journal = {Journal of Applied Physics}, Volume = {122}, Number = {2}, Pages = {024902}, Year = {2017}, Month = {July}, url = {http://dx.doi.org/10.1063/1.4991642}, Abstract = {High-volume production of hyperpolarized 129Xe by spin-exchange optical pumping (SEOP) has historically fallen short of theoretical predictions. Recently, this shortfall was proposed to be caused by the formation of alkali metal clusters during optical pumping. However, this hypothesis has yet to be verified experimentally. Here, we seek to detect the presence of alkali particles using a combination of both transmission (TEM) and scanning (SEM) electron microscopy. From TEM studies, we observe the presence of particles exhibiting sizes ranging from approximately 0.2 to 1 μm and present at densities of order 10 s of particles per 100 square microns. Particle formation was more closely associated with extensive cell usage history than short-term ([Formula: see text]1 h) SEOP exposure. From the SEM studies, we observe pits on the cell surface. These pits are remarkably smooth, were frequently found adjacent to Rb particles, and located predominantly on the front face of the cells; they range in size from 1 to 5 μm. Together, these findings suggest that Rb particles do form during the SEOP process and at times can impart sufficient energy to locally alter the Pyrex surface.}, Doi = {10.1063/1.4991642}, Key = {fds327669} } @article{fds328953, Author = {Wang, JM and Robertson, SH and Wang, Z and He, M and Virgincar, RS and Schrank, GM and Smigla, RM and O'Riordan, TG and Sundy, J and Ebner, L and Rackley, CR and McAdams, P and Driehuys, B}, Title = {Using hyperpolarized (129)Xe MRI to quantify regional gas transfer in idiopathic pulmonary fibrosis.}, Journal = {Thorax}, Year = {2017}, Month = {August}, url = {http://dx.doi.org/10.1136/thoraxjnl-2017-210070}, Abstract = {Assessing functional impairment, therapeutic response and disease progression in patients with idiopathic pulmonary fibrosis (IPF) continues to be challenging. Hyperpolarized (129)Xe MRI can address this gap through its unique capability to image gas transfer three-dimensionally from airspaces to interstitial barrier tissues to red blood cells (RBCs). This must be validated by testing the degree to which it correlates with pulmonary function tests (PFTs) and CT scores, and its spatial distribution reflects known physiology and patterns of disease.13 healthy individuals (33.6±15.7 years) and 12 patients with IPF (66.0±6.4 years) underwent (129)Xe MRI to generate three-dimensional quantitative maps depicting the (129)Xe ventilation distribution, its uptake in interstitial barrier tissues and its transfer to RBCs. For each map, mean values were correlated with PFTs and CT fibrosis scores, and their patterns were tested for the ability to depict functional gravitational gradients in healthy lung and to detect the known basal and peripheral predominance of disease in IPF.(129)Xe MRI depicted functional impairment in patients with IPF, whose mean barrier uptake increased by 188% compared with the healthy reference population. (129)Xe MRI metrics correlated poorly and insignificantly with CT fibrosis scores but strongly with PFTs. Barrier uptake and RBC transfer both correlated significantly with diffusing capacity of the lungs for carbon monoxide (r=-0.75, p<0.01 and r=0.72, p<0.01), while their ratio (RBC/barrier) correlated most strongly (r=0.94, p<0.01). RBC transfer exhibited significant anterior-posterior gravitational gradients in healthy volunteers, but not in IPF, where it was significantly impaired in the basal (p=0.02) and subpleural (p<0.01) lung.Hyperpolarized(129)Xe MRI is a rapid and well-tolerated exam that provides region-specific quantification of interstitial barrier thickness and RBC transfer efficiency. With further development, it could become a robust tool for measuring disease progression and therapeutic response in patients with IPF, sensitively and non-invasively.}, Doi = {10.1136/thoraxjnl-2017-210070}, Key = {fds328953} } @article{fds329557, Author = {Song, EJ and Kelsey, CR and Driehuys, B and Rankine, L}, Title = {Functional airway obstruction observed with hyperpolarized 129 Xenon-MRI.}, Journal = {Journal of Medical Imaging and Radiation Oncology}, Year = {2017}, Month = {September}, url = {http://dx.doi.org/10.1111/1754-9485.12660}, Abstract = {Hyperpolarized 129 Xenon-MRI (HP 129 Xe MRI) is an emerging imaging modality that allows assessment of both ventilation and gas transfer. Most research to date has focused on non-malignant pulmonary diseases. However, the capability of evaluating the two primary physiological processes of the lung (ventilation and gas transfer) makes HP 129 Xe MRI a promising imaging modality in the management of patients with lung cancer.}, Doi = {10.1111/1754-9485.12660}, Key = {fds329557} } @article{fds329556, Author = {Robertson, SH and Virgincar, RS and Bier, EA and He, M and Schrank, GM and Smigla, RM and Rackley, C and McAdams, HP and Driehuys, B}, Title = {Uncovering a third dissolved-phase 129 Xe resonance in the human lung: Quantifying spectroscopic features in healthy subjects and patients with idiopathic pulmonary fibrosis.}, Journal = {Magnetic Resonance in Medicine}, Volume = {78}, Number = {4}, Pages = {1306-1315}, Year = {2017}, Month = {October}, url = {http://dx.doi.org/10.1002/mrm.26533}, Abstract = {The purpose of this work was to accurately characterize the spectral properties of hyperpolarized 129 Xe in patients with idiopathic pulmonary fibrosis (IPF) compared to healthy volunteers.Subjects underwent hyperpolarized 129 Xe breath-hold spectroscopy, during which 38 dissolved-phase free induction decays (FIDs) were acquired after reaching steady state (echo time/repetition time = 0.875/50 ms; bandwidth = 8.06 kHz; flip angle≈22 °). FIDs were averaged and then decomposed into multiple spectral components using time-domain curve fitting. The resulting amplitudes, frequencies, line widths, and starting phases of each component were compared among groups using a Mann-Whitney-Wilcoxon U test.Three dissolved-phase resonances, consisting of red blood cells (RBCs) and two barrier compartments, were consistently identified in all subjects. In subjects with IPF relative to healthy volunteers, the RBC frequency was 0.70 parts per million (ppm) more negative (P = 0.05), the chemical shift of barrier 2 was 0.6 ppm more negative (P = 0.009), the line widths of both barrier peaks were ∼2 ppm narrower (P < 0.001), and the starting phase of barrier 1 was 20.3 ° higher (P =  0.01). Moreover, the ratio RBC:barriers was reduced by 52.9% in IPF (P < 0.001).The accurate decomposition of 129 Xe spectra not only has merit for developing a global metric of pulmonary function, but also provides necessary insights to optimize phase-sensitive methods for imaging 129 Xe gas transfer. Magn Reson Med 78:1306-1315, 2017. © 2016 International Society for Magnetic Resonance in Medicine.}, Doi = {10.1002/mrm.26533}, Key = {fds329556} }