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| Publications of Nimmi Ramanujam :chronological alphabetical combined listing:
%% Books
@book{fds195293,
Title = {Handbook of Biomedical Optics},
Publisher = {CRC Press},
Editor = {Boas DA and Pitris C and Ramanujam N.},
Year = {2011},
Key = {fds195293}
}
%% Book Chapters
@misc{fds215733,
Author = {Vishwanath K and Palmer GM and Brown JQ and Ramanujam
N},
Title = {Non-invasive and quantitative sensing of tumor physiology
and function via steady-state diffuse optical
spectroscopy},
Booktitle = {Biosensors and Biodetection Technologies for Cancer
Detection, Diagnostics and Research},
Year = {2012},
Key = {fds215733}
}
@misc{fds194862,
Author = {Ramanujam N and Vishwanath K and Palmer GM and Brown
JQ},
Title = {Non-invasive and quantitative sensing of tumor physiology
and function via steady-state diffuse optical
spectroscopy},
Series = {in Biosensors and biodetection technologies for cancer
detection, diagnostics and research},
Publisher = {CRC Press},
Editor = {Rasooly, A. and Herold, K.},
Year = {2011},
Key = {fds194862}
}
@misc{fds194863,
Author = {Brown JQ and Vishwanath K and Chang TVC and Ramanujam
N},
Title = {Clinical Applications of UV-VIS Optical Spectroscopy in
Cervix, Head and Neck, and Breast Cancer},
Pages = {239-285},
Booktitle = {In Vivo Clinical Imaging and Diagnosis},
Editor = {J. Tunnell},
Year = {2011},
Key = {fds194863}
}
@misc{fds169271,
Author = {Brown JQ and Bydlon TM and Richards LM and Yu B and Kennedy SA and Wilke
LG, Geradts J and Junker M and Gallagher J and Ramanujam
N},
Title = {Optical assessment of tumor resection margins in the
breast},
Volume = {20},
Pages = {119-131},
Booktitle = {IEEE Journal of Selected Topics on Quantum
Electronics},
Year = {2010},
Key = {fds169271}
}
@misc{fds169270,
Author = {Skala MC and Ramanujam N.},
Title = {Multiphoton Redox Ratio Imaging for Metabolic Monitoring in
vivo},
Volume = {594},
Pages = {155-162},
Booktitle = {Advanced Protocols in Oxidative Stress},
Editor = {Ed. Don Armstrong},
Year = {2010},
Key = {fds169270}
}
@misc{fds169269,
Author = {Brown JQ and Vishwanath K and Palmer GM and Ramanujam
N.},
Title = {Advances in quantitative UV-visible spectroscopy for
clinical and pre-clinical application in
cancer},
Volume = {20},
Pages = {119-131},
Booktitle = {Current Opinion in Biotechnology},
Year = {2009},
Key = {fds169269}
}
@misc{fds71331,
Author = {Palmer GM and Ramanujam N},
Title = {Diagnosis of breast cancer using optical
spectroscopy},
Volume = {18},
Number = {3},
Pages = {233-48},
Booktitle = {Medical Laser Applications},
Year = {2003},
Key = {fds71331}
}
@misc{fds71330,
Author = {Gill EM and Palmer GM and Ramanujam N},
Title = {Steady-state fluorescence imaging of Neoplasia},
Volume = {361},
Pages = {452-481},
Booktitle = {Methods in Enzymology},
Publisher = {Academic Press},
Year = {2003},
Key = {fds71330}
}
@misc{fds71328,
Author = {Ramanujam N},
Title = {Fluorescence spectroscopy of neoplastic and non-neoplastic
tissues},
Booktitle = {Neoplasia},
Year = {2000},
Key = {fds71328}
}
@misc{fds71329,
Author = {Ramanujam N},
Title = {Fluorescence Spectroscopy In Vivo},
Pages = {20-56},
Booktitle = {Encyclopedia of Analytical Chemistry},
Publisher = {ohn Wiley & Sons},
Year = {2000},
Key = {fds71329}
}
@misc{fds71327,
Author = {Ramanujam N and Boas DA and Li Y},
Title = {Laser spectroscopy and imaging for characterization of
tissue, In: Lasers in Surface Engineering},
Booktitle = {ASM International Materials Park OH, 523-594},
Year = {1998},
Key = {fds71327}
}
@misc{fds71326,
Author = {Ramanujam N and Mitchell MF and Mahadevan A and Thomsen S and Silva E and Richards-Kortum RR},
Title = {Fluorescence spectroscopy: a diagnostic tool for Cervical
Intraepithelial Neoplasia, In: Female Genital
Tract},
Booktitle = {Stoler MH (Eds.) Mosby-Year Book},
Year = {1995},
Key = {fds71326}
}
%% Papers Published
@article{fds217444,
Author = {Lo JY and Brown JQ and Dhar S and Yu B and Jokerst NM and Ramanujam
N},
Title = {Wavelength optimization for quantitative spectral imaging of
breast tumor margins},
Journal = {PLoS ONE},
Year = {2013},
Month = {April},
Key = {fds217444}
}
@article{fds217443,
Author = {Zhong J and Rajaram N and Brizel DM and Frees AE and Ramanujam N and Batinic-Haberle I and Dewhirst MW},
Title = {Radiation induces aerobic glycolysis through reactive oxygen
species},
Journal = {Radiotherapy and Oncology},
Year = {2013},
Month = {March},
Key = {fds217443}
}
@article{fds217610,
Author = {Fu H and Mueller J and Javid M and Mito J and Kirsch D and Ramanujam N and Brown Q},
Title = {Optimization of a Widefield Structured Illumination
Microscope for Non-Destructive Assessment and Quantification
of Nuclear Features in Tumor Margins of a Primary Mouse
Model of Sarcoma},
Journal = {PLoS one},
Year = {2013},
Key = {fds217610}
}
@article{fds217445,
Author = {Mueller J and Harmany Z and Mito K and Kennedy S and Kim Y and Dodd L and Geradts J and Kirsch D and Willett R and Brown Q and Ramanujam
N},
Title = {Quantitative segmentation of fluorescence microscopy images
of heterogeneous tissue: Application to the detection of
residual disease in tumor margins},
Year = {2013},
Key = {fds217445}
}
@article{fds217442,
Author = {Brown JQ and Ramanujam N},
Title = {Leveraging tissue composition and micro-morpholoy or breast
tumor margin assessment via quantitative diffuse optical
spectral imaging},
Journal = {PLoS ONE},
Year = {2013},
Key = {fds217442}
}
@article{fds215734,
Author = {Liu C and Rajaram N and Vishwanath K and Jiang T and Palmer G and N.
Ramanujam},
Title = {Experimental Validation of an Inverse Fluorescence Monte
Carlo Model to Extract Concentrations of Metabolically
Relevant Fluorophores from Turbid Phantoms and a Murine
Tumor Model},
Journal = {Journal of Biomedical Optics},
Year = {2012},
Key = {fds215734}
}
@article{fds215735,
Author = {Dhar S and Lo JY and Palmer GM and Brooke MA and Nichols BS and Yu B and Ramanujam N and Jokerst NM},
Title = {A diffuse reflectance spectral imaging system for tumor
margin assessment using custom annular photodiode
arrays},
Journal = {Biomedical Optics Express},
Volume = {3},
Number = {12},
Pages = {3211-3222},
Year = {2012},
Key = {fds215735}
}
@article{fds215736,
Author = {Bydlon TM and Barry WT and Kennedy SA and Brown JQ and Gallagher JE and Ramanujam N},
Title = {Advancing Optical Imaging for Breast Margin Assessment: An
Analysis of Excisional Time, Cautery, and Patent Blue Dye on
Underlying Sources of Contrast},
Journal = {PLoS ONE},
Year = {2012},
Key = {fds215736}
}
@article{fds215737,
Author = {Yu B and Shah A and Wang B and Rajaram N and Wang Q and Ramanujam N and Palmer
GM, Dewhirst MW},
Title = {Measuring tumor cycling hypoxia and angiogenesis using a
side-firing fiber optic probe},
Journal = {Journal of Biophotonics},
Year = {2012},
Key = {fds215737}
}
@article{fds195265,
Author = {Vishwanath K and Chang K and Klein D and Chang V and Deng YF and Phelps JE and Ramanujam N},
Title = {Portable Fiber Based Diffuse Reflectance Spectroscopy
Systems for Estimating Tissue Optical Parameters},
Journal = {Applied Spectroscopy},
Volume = {65},
Number = {2},
Pages = {011010-12},
Year = {2011},
Key = {fds195265}
}
@article{fds195266,
Author = {Beumer, W.H. and Vishwanath, K. and Puscas, L. and Afshari, H. and Ramanujam, N. and Lee, W},
Title = {Detection of Squamous Cell Carcinoma and corresponding
biomarkers using optical spectroscopy},
Journal = {Otolaryngology Head and Neck Surgery},
Volume = {144},
Number = {3},
Pages = {390-394},
Year = {2011},
Key = {fds195266}
}
@article{fds195268,
Author = {Lo JY and Yu B and Kuech TF and Ramanujam N},
Title = {A compact, cost-effective diffuse reflectance spectroscopic
imaging system for quantitative tissue absorption and
scattering},
Journal = {Proc. of SPIE, Vol. 7890, San Francisco,
CA.},
Year = {2011},
Key = {fds195268}
}
@article{fds195270,
Author = {Yu B and Fu HL and Ramanujam N},
Title = {Instrument-Independent Diffuse Reflectance
Spectroscopy},
Journal = {JBO},
Volume = {16},
Number = {1},
Pages = {011010},
Year = {2011},
Key = {fds195270}
}
@article{fds195271,
Author = {Chang VTC and Merisier D and Yu B and Walmer DK and Ramanujam
N},
Title = {Towards a field-compatible optical Spectroscopic device for
cervical cancer screening in resource-limited settings:
effects of calibration and pressure},
Journal = {Optics Express, in press},
Year = {2011},
Key = {fds195271}
}
@article{fds195256,
Author = {Millon SR and Ostrander JH and Brown JQ and Rajeha AM and Seewaldt VL and Ramanujam N},
Title = {Uptake of 2-NBDG as a method to monitor therapy response in
breast cancer cell lines},
Journal = {Breast Cancer Research and Treatment},
Volume = {126},
Number = {1},
Pages = {55-62},
Year = {2011},
Key = {fds195256}
}
@article{fds190023,
Author = {J.H. Ostrander and C.M. McMahon and S. Lem and S.R. Millon and V.L.
Seewaldt, N. Ramanujam},
Title = {The Optical Redox Ratio Differentiates Breast Cancer Cell
Lines Based on Receptor Status},
Journal = {Cancer Research},
Volume = {70},
Number = {11},
Pages = {4759-4766},
Year = {2010},
Key = {fds190023}
}
@article{fds195252,
Author = {Bydlon TM and Kennedy SA and Richards LM and Brown JQ and Yu B and Junker
MS, Gallagher J and Geradts J and Wilke LG and Ramanujam
N},
Title = {Performance metrics of an optical spectral imaging system
for intra-operative assessment of breast tumor
margins},
Journal = {Optics Express},
Volume = {19},
Number = {8},
Pages = {8058-8076},
Year = {2010},
Key = {fds195252}
}
@article{fds195253,
Author = {Chang VTC and Bean SM and Cartwright PS and Ramanujam
N},
Title = {CD34 Immunohistochemical Validation of Increased Hemoglobin
through Optical Spectroscopy in the Precancerous
Cervix},
Journal = {JBO},
Volume = {15},
Number = {5},
Year = {2010},
Key = {fds195253}
}
@article{fds195254,
Author = {Fu HL and Yu B and Lo JY and Palmer GM and Kuech TF and Ramanujam
N},
Title = {A Cost-Effective, Portable, and Quantitative Spectral
Imaging System for Application to Biological
Tissues},
Journal = {Optics Express},
Volume = {18},
Number = {12},
Pages = {12630-12645},
Year = {2010},
Key = {fds195254}
}
@article{fds195257,
Author = {Gill EM and Straseki JA and Rasmussen CA and Liliensiek SJ and Eliceiri
KW, Ramanujam N},
Title = {Visualization of morphological and molecular features
associated with chronic ischemia in bioengineered human
skin},
Journal = {Microsc Microanal},
Volume = {16},
Number = {2},
Pages = {117-131},
Year = {2010},
Key = {fds195257}
}
@article{fds195258,
Author = {Phelps JE and Vishwanath K and Chang VTC and Ramanujam
N},
Title = {Rapid ratiometric determination of hemoglobin concentration
using UV-VIS diffuse reflectance at isosbestic
wavelengths},
Journal = {Optics Express},
Volume = {18},
Number = {18},
Pages = {18779-18792},
Year = {2010},
Key = {fds195258}
}
@article{fds195260,
Author = {Brown JQ and Bydlon TM and Richards LM and Yu B and Kennedy SA and Geradts
J, Wilke LG and Junker M and Gallagher J and Barry W and Ramanujam
N},
Title = {Optical assessment of tumor resection margins in the
breast},
Journal = {IEEE Journal of Selected Topics in Quantum
Electronics},
Volume = {12},
Number = {3},
Pages = {530-544},
Year = {2010},
Key = {fds195260}
}
@article{fds195262,
Author = {Kennedy SA and Geradts G and Bydlon T and Brown JQ and Gallagher J and Junker M and Barry W and Ramanujam N and Wilke L},
Title = {Optical breast cancer margin assessment: an observational
study of the effects of tissue heterogeneity on optical
contrast},
Journal = {Breast Cancer Research},
Volume = {12},
Number = {6},
Pages = {R91},
Year = {2010},
Key = {fds195262}
}
@article{fds169275,
Author = {Millon SR and Ostrander JH and Yazdanfar S and Brown JQ and Raheja AM and Ramanujam N.},
Title = {Preferential accumulation of 5-aminolevulinic acid-induced
protoporphyrin IX in breast cancer: A comprehensive study on
six breast cell lines with varying phenotypes},
Journal = {Journal of Biomedical Optics},
Volume = {15},
Number = {1},
Pages = {018002},
Year = {2010},
Key = {fds169275}
}
@article{fds169274,
Author = {J. E. Bender and A. B. Shang and E. W. Moretti and B. Yu and L. M.
Richards and N. Ramanujam},
Title = {Noninvasive Monitoring of Tissue Hemoglobin Using UV-VIS
Diffuse Reflectance Spectroscopy: A Pilot
Study},
Journal = {Optics Express},
Volume = {17},
Number = {26},
Pages = {23396-23409},
Year = {2009},
Month = {December},
Key = {fds169274}
}
@booklet{Wilke09,
Author = {L. G. Wilke and J. Q. Brown and T. M. Bydlon and S. A.
Kennedy and L. M. Richards and M. K. Junker and J. Gallagher and W. T. Barry and J. Geradts and N. Ramanujam},
Title = {Rapid noninvasive optical imaging of tissue composition in
breast tumor margins},
Journal = {American Journal Of Surgery},
Volume = {198},
Number = {4},
Pages = {566 -- 574},
Year = {2009},
Month = {October},
ISSN = {0002-9610},
Abstract = {BACKGROUND: In women undergoing breast conserving surgery
(BCS), up to 60\% can require re-excision. Our objective is
to develop an optically based technology which can
differentiate benign from malignant breast tissues
intraoperatively through differences in tissue composition
factors. METHODS: A prospective study of optical imaging of
BCS margins is being performed. Optical images are
transformed into tissue composition maps with parameters of
total hemoglobin concentration, b-carotene concentration and
scattering. The predicted outcome is then compared to the
margin-level pathology. RESULTS: Fifty-five margins from 48
patients have undergone assessment. Within 34 specimens with
pathologically confirmed positive margins, the ratio map of
b-carotene/scattering showed the most significant difference
reflecting a decrease in adipose and an increase in cell
density within malignant margins (p=.002). These differences
were notable in both in-situ and invasive disease.
CONCLUSIONS: We present a novel optical spectral imaging
device that provides a rapid, non-destructive assay of the
tissue composition of breast tumor margins. (C) 2009
Elsevier Inc. All rights reserved.},
Key = {Wilke09}
}
@booklet{Zhu09,
Author = {C. F. Zhu and E. S. Burnside and G. A. Sisney and L. R.
Salkowski and J. M. Harter and B. Yu and N.
Ramanujam},
Title = {Fluorescence Spectroscopy: An Adjunct Diagnostic Tool to
Image-Guided Core Needle Biopsy of the Breast},
Journal = {Ieee Transactions On Biomedical Engineering},
Volume = {56},
Number = {10},
Pages = {2518 -- 2528},
Year = {2009},
Month = {October},
ISSN = {0018-9294},
Abstract = {We explored the use of a fiber-optic probe for in vivo
fluorescence spectroscopy of breast tissues during
percutaneous image-guided breast biopsy. A total of 121
biopsy samples with accompanying histological diagnosis were
obtained clinically and investigated in this study. The
tissue spectra were analyzed using partial least-squares
analysis and represented using a set of principal components
(PCs) with dramatically reduced data dimension. For
nonmalignant tissue samples, a set of PCs that account for
the largest amount of variance in the spectra displayed
correlation with the percent tissue composition. For all
tissue samples, a set of PCs was identified using a Wilcoxon
rank-sum test as showing statistically significant
differences between: 1) malignant and fibrous/benign; 2)
malignant and adipose; and 3) malignant and nonmalignant
breast samples. These PCs were used to distinguish malignant
from other nonmalignant tissue types using a binary
classification scheme based on both linear and nonlinear
support vector machine (SVM) and logistic regression (LR).
For the sample set investigated in this study, the SVM
classifier provided a cross-validated sensitivity and
specificity of up to 81\% and 87\%, respectively, for
discrimination between malignant and fibrous/benign samples,
and up to 81\% and 81\%, respectively, for discriminating
between malignant and adipose samples. Classification based
on LR was used to generate receiver operator curves with an
area under the curve (AUC) of 0.87 for discriminating
malignant versus fibrous/benign tissues, and an AUC of 0.84
for discriminating malignant from adipose tissue samples.
This study demonstrates the feasibility of performing
fluorescence spectroscopy during clinical core needle breast
biopsy, and the potential of this technique for identifying
breast malignancy in vivo.},
Key = {Zhu09}
}
@booklet{Vishwanath09,
Author = {K. Vishwanath and D. Klein and K. Chang and T. Schroeder and M. W. Dewhirst and N. Ramanujam},
Title = {Quantitative optical spectroscopy can identify long-term
local tumor control in irradiated murine head and neck
xenografts},
Journal = {Journal Of Biomedical Optics},
Volume = {14},
Number = {5},
Year = {2009},
Month = {September},
ISSN = {1083-3668},
Abstract = {Noninvasive and longitudinal monitoring of tumor oxygenation
status using quantitative diffuse reflectance spectroscopy
is used to test whether a final treatment outcome could be
estimated from early optical signatures in a murine model of
head and neck cancer when treated with radiation. Implanted
tumors in the flank of 23 nude mice are exposed to 39 Gy of
radiation, while 11 animals exposed to sham irradiation
serve as controls. Diffuse optical reflectance is measured
from the tumors at baseline (prior to irradiation) and then
serially until 17 days posttreatment. The fastest and
greatest increase in baseline-corrected blood oxygen
saturation levels are observed from the animals that show
complete tumor regression with no recurrence 90 days
postirradiation, relative to both untreated and treated
animals with local recurrences. These increases in
saturation are observed starting 5 days posttreatment and
last up to 17 days posttreatment. This preclinical study
demonstrates that diffuse reflectance spectroscopy could
provide a practical method far more effective than the
growth delay assay to prognosticate treatment outcome in
solid tumors and may hold significant translational promise.
(C) 2009 Society of Photo-Optical Instrumentation Engineers.
[DOI: 10.1117/1.3251013]},
Key = {Vishwanath09}
}
@booklet{Vishwanath09a,
Author = {K. Vishwanath and H. Yuan and W. T. Barry and M. W. Dewhirst and N. Ramanujam},
Title = {Using Optical Spectroscopy to Longitudinally Monitor
Physiological Changes within Solid Tumors},
Journal = {Neoplasia},
Volume = {11},
Number = {9},
Pages = {889 -- 900},
Year = {2009},
Month = {September},
ISSN = {1522-8002},
Abstract = {The feasibility of using quantitative diffuse reflectance
spectroscopy to longitudinally monitor physiological
response to cancer therapy was evaluated in a preclinical
model. This study included two groups of nude mice bearing
4T1 flank tumors (N = 50), half of which were treated with a
maximum tolerated dose of doxorubicin (DOX). Diffuse
reflectance spectra were collected from tumors during a
period of 2 weeks using a fiber-optic probe coupled to a
spectrometer. These spectra were quantified using an inverse
scalable Monte Carlo model of light transport in tissue to
extract the concentrations of oxygenated, deoxygenated
hemoglobin (dHb), and a wavelength mean reduced scattering
coefficient ($<$mu(s)'$>$). The tumor growth rates of the
treated and control groups were nearly identical, as were
changes in the scattering parameter $<$mu(s)'$>$ during this
time frame. However, tumors treated with DOX showed a
transient but significant increase in blood oxygen
saturation. A comparison between the optically derived and
immunohistochemical end points in a subset of the 50 animals
showed that the temporal kinetics of dHb concentration and
$<$mu(s)'$>$ were highly concordant with those of hypoxic
and necrotic fractions, respectively. In conclusion, optical
methods could function as a "screening" technology in
longitudinal studies of small animal tumor models to
accelerate development and testing of new anticancer drugs.
This technique could isolate specific landmark time points
at which more expensive and sophisticated imaging methods or
immunohistochemistry could be performed.},
Key = {Vishwanath09a}
}
@booklet{Bender09,
Author = {J. E. Bender and K. Vishwanath and L. K. Moore and J. Q.
Brown and V. Chang and G. M. Palmer and N.
Ramanujam},
Title = {A Robust-Monte Carlo Model for the Extraction of Biological
Absorption and Scattering In Vivo},
Journal = {Ieee Transactions On Biomedical Engineering},
Volume = {56},
Number = {4},
Pages = {960 -- 968},
Year = {2009},
Month = {April},
ISSN = {0018-9294},
Abstract = {We have a toolbox to quantify tissue optical properties that
is composed of specialized fiberoptic probes for UV-visible
diffuse reflectance spectroscopy and a fast, scalable
inverse Monte Carlo (MC) model. In this paper, we assess the
robustness of the toolbox for quantifying physiologically
relevant parameters from turbid tissue-like media. In
particular, we consider the effects of using different
instruments, fiberoptic probes, and instrument-specific
settings for a wide range of optical properties.
Additionally, we test the quantitative accuracy of the
inverse MC model for extracting the biologically relevant
parameters of hemoglobin saturation and total hemoglobin
concentration. We also test the effect of double-absorber
phantoms (hemoglobin and crocin to model the absorption of
hemoglobin and beta carotene, respectively, in the breast)
for a range of absorption and scattering properties. We
include an assessment on which reference phantom serves as
the best calibration standard to enable accurate extraction
of the absorption and scattering properties of the target
sample. We found the best reference-target phantom
combinations to be ones with similar scattering levels. The
results from these phantom studies provide a set of
guidelines for extracting optical parameters from clinical
studies.},
Key = {Bender09}
}
@booklet{Brown09a,
Author = {J. Q. Brown and L. G. Wilke and J. Geradts and S. A. Kennedy and G. M. Palmer and N. Ramanujam},
Title = {Quantitative Optical Spectroscopy: A Robust Tool for Direct
Measurement of Breast Cancer Vascular Oxygenation and Total
Hemoglobin Content In vivo},
Journal = {Cancer Research},
Volume = {69},
Number = {7},
Pages = {2919 -- 2926},
Year = {2009},
Month = {April},
ISSN = {0008-5472},
Abstract = {We propose the use of a robust, biopsy needle-based,
fiber-optic tool for routine clinical quantification of
tumor oxygenation at the time of diagnostic biopsy for
breast cancer. The purpose of this study was to show diffuse
reflectance spectroscopy as a quantitative tool to measure
oxygenation levels in the vascular compartment of breast
cancers in vivo via an optical biopsy technique. Thirty-five
patients undergoing surgical treatment for breast cancer
were recruited for the study at Duke University Medical
Center. Diffuse reflectance spectroscopy was performed on
the tumors in situ before surgical resection, followed by
needle-core biopsy of the optically measured tissue.
Hemoglobin saturation and total hemoglobin content were
quantified from 76 optical spectra-tissue biopsy pairs,
consisting of 20 malignant, 23 benign, and 33 adipose
tissues. Hemoglobin saturation in malignant tissues was
significantly lower than nonmalignant tissues (P $<$ 0.002)
and was negatively correlated with tumor size and pathologic
tumor category (P $<$ 0.05). Hemoglobin saturation was
positively correlated with total hemoglobin content in
malignant tissues (P $<$ 0.02). HER2/neu-amplified tumors
exhibited significantly higher total hemoglobin content (P
$<$ 0.05) and significantly higher hemoglobin saturation (P
$<$ 0.02), which is consistent with a model of increased
angiogenesis and tumor perfusion promoted by HER2/neu
amplification. Diffuse reflectance spectroscopy could aid in
prognosis and prediction in breast cancer via quantitative
assessment of tumor physiology at the time of diagnostic
biopsy. [Cancer Res 2009;69(7):2919-26]},
Key = {Brown09a}
}
@booklet{Palmer09,
Author = {G. M. Palmer and R. J. Viola and T. Schroeder and P. S.
Yarmolenko and M. W. Dewhirst and N. Ramanujam},
Title = {Quantitative diffuse reflectance and fluorescence
spectroscopy: tool to monitor tumor physiology in
vivo},
Journal = {Journal Of Biomedical Optics},
Volume = {14},
Number = {2},
Year = {2009},
Month = {March},
ISSN = {1083-3668},
Abstract = {This study demonstrates the use of optical spectroscopy for
monitoring tumor oxygenation and metabolism in response to
hyperoxic gas breathing. Hemoglobin saturation and redox
ratio were quantified for a set of 14 and 9 mice,
respectively, measured at baseline and during carbogen
breathing (95\% O-2, 5\% CO2). In particular, significant
increases in hemoglobin saturation and fluorescence redox
ratio were observed upon carbogen breathing. These data were
compared with data obtained concurrently using an
established invasive technique, the OxyLite partial oxygen
pressure (pO(2)) system, which also showed a significant
increase in pO2. It was found that the direction of changes
were generally the same between all of the methods, but that
the OxyLite system was much more variable in general,
suggesting that optical techniques may provide a better
assessment of global tumor physiology. Optical spectroscopy
measurements are demonstrated to provide a reliable,
reproducible indication of changes in tumor physiology in
response to physiologic manipulation. (C) 2009 Society of
Photo-Optical Instrumentation Engineers. [DOI:
10.1117/1.3103586]},
Key = {Palmer09}
}
@booklet{Brown09,
Author = {J. Q. Brown and K. Vishwanath and G. M. Palmer and N.
Ramanujam},
Title = {Advances in quantitative UV-visible spectroscopy for
clinical and pre-clinical application in
cancer},
Journal = {Current Opinion In Biotechnology},
Volume = {20},
Number = {1},
Pages = {119 -- 131},
Year = {2009},
Month = {February},
ISSN = {0958-1669},
Abstract = {Methods of optical spectroscopy that provide quantitative,
physically or physiologically meaningful measures of tissue
properties are an attractive tool for the study, diagnosis,
prognosis, and treatment of various cancers. Recent
development of methodologies to convert measured reflectance
and fluorescence spectra from tissue to cancer-relevant
parameters such as vascular volume, oxygenation,
extracellular matrix extent, metabolic redox states, and
cellular proliferation have significantly advanced the field
of tissue optical spectroscopy. The number of publications
reporting quantitative tissue spectroscopy results in the
UV-visible wavelength range has increased sharply in the
past three years, and includes new and emerging studies that
correlate optically measured parameters with independent
measures such as immunohistochemistry, which should aid in
increased clinical acceptance of these technologies.},
Key = {Brown09}
}
@booklet{Lo09,
Author = {J. Y. Lo and B. Yu and H. L. Fu and J. E. Bender and G. M.
Palmer and T. F. Kuech and N. Ramanujam},
Title = {A strategy for quantitative spectral imaging of tissue
absorption and scattering using light emitting diodes and
photodiodes},
Journal = {Optics Express},
Volume = {17},
Number = {3},
Pages = {1372 -- 1384},
Year = {2009},
Month = {February},
ISSN = {1094-4087},
Abstract = {A diffuse reflectance spectroscopy system was modified as a
step towards miniaturization and spectral imaging of tissue
absorption and scattering. The modified system uses a
tunable source and an optical fiber for illumination and a
photodiode in contact with tissue for detection. Compared to
the previous system, it is smaller, less costly, and has
comparable performance in extracting optical properties in
tissue phantoms. Wavelength reduction simulations show the
feasibility of replacing the source with LEDs to further
decrease system size and cost. Simulated crosstalk analysis
indicates that this evolving system can be multiplexed for
spectral imaging in the future. (C) 2009 Optical Society of
America},
Key = {Lo09}
}
@booklet{Brown09b,
Author = {J. Q. Brown and T. M. Bydlon and S. A. Kennedy and L.
Richards and M. S. Junker and G. M. Palmer and J. Geradts and L. G. Wilke and N. Ramanujam},
Title = {Intraoperative optical breast tissue characterization device
for tumor margin assessment},
Journal = {Cancer Research},
Volume = {69},
Number = {2},
Pages = {101S -- 101S},
Year = {2009},
Month = {January},
ISSN = {0008-5472},
Key = {Brown09b}
}
@article{fds169273,
Author = {Chang VTC and Cartwright PS and Bean SM and Palmer GM and Bentley RC and Ramanujam N.},
Title = {Quantitative physiology of the precancerous cervix in vivo
via optical spectroscopy},
Journal = {Neoplasia},
Volume = {11},
Number = {4},
Pages = {325-332},
Year = {2009},
Key = {fds169273}
}
@booklet{Yu08,
Author = {B. Yu and J. Y. Lo and T. F. Kuech and G. M. Palmer and J.
E. Bender and N. Ramanujam},
Title = {Cost-effective diffuse reflectance spectroscopy device for
quantifying tissue absorption and scattering in
vivo},
Journal = {Journal Of Biomedical Optics},
Volume = {13},
Number = {6},
Year = {2008},
Month = {November},
ISSN = {1083-3668},
Abstract = {A hybrid optical device that uses a multimode fiber coupled
to a tunable light source for illumination and a 2.4-mm
photodiode for detection in contact with the tissue surface
is developed as a first step toward our goal of developing a
cost-effective, miniature spectral imaging device to map
tissue optical properties in vivo. This device coupled with
an inverse Monte Carlo model of reflectance is demonstrated
to accurately quantify tissue absorption and scattering in
tissue-like turbid synthetic phantoms with a wide range of
optical properties. The overall errors for quantifying the
absorption and scattering coefficients are 6.0 +/- 5.6 and
6.1 +/- 4.7\%, respectively. Compared with fiber-based
detection, having the detector right at the tissue surface
can significantly improve light collection efficiency, thus
reducing the requirement for sophisticated detectors with
high sensitivity, and this design can be easily expanded
into a quantitative spectral imaging system for mapping
tissue optical properties in vivo. (C) 2008 Society of
Photo-Optical Instrumentation Engineers. [DOI:
10.1117/1.3041500]},
Key = {Yu08}
}
@booklet{Lazebnik08,
Author = {M. Lazebnik and C. F. Zhu and G. M. Palmer and J. Harter and S. Sewall and N. Ramanujam and S. C. Hagness},
Title = {Electromagnetic Spectroscopy of Normal Breast Tissue
Specimens Obtained From Reduction Surgeries: Comparison of
Optical and Microwave Properties},
Journal = {Ieee Transactions On Biomedical Engineering},
Volume = {55},
Number = {10},
Pages = {2444 -- 2451},
Year = {2008},
Month = {October},
ISSN = {0018-9294},
Abstract = {Techniques utilizing electromagnetic energy at microwave and
optical frequencies have been shown to be promising for
breast cancer detection and diagnosis. Since different
biophysical mechanisms are exploited at these frequencies to
discriminate between healthy and diseased tissue, combining
these two modalities may result in a more powerful approach
for breast cancer detection and diagnosis. Toward this end,
we performed microwave dielectric spectroscopy and optical
diffuse reflectance spectroscopy measurements at the same
sites on freshly excised normal breast tissues obtained from
reduction surgeries at the University of Wisconsin Hospital,
using microwave and optical probes with very similar sensing
volumes. We found that the microwave dielectric constant and
effective conductivity are correlated with tissue
composition across the entire measurement frequency range
(vertical bar r vertical bar similar to 0.5-0.6, p $<$ 0.01)
and that the optical absorption coefficient at 460 nm and
optical scattering coefficient are correlated with tissue
composition (vertical bar r vertical bar similar to 0.4-0.6,
p $<$ 0.02). Finally, we found that the optical absorption
coefficient at 460 nm is correlated with the microwave
dielectric constant and effective conductivity (r = -0.55, p
$<$ 0.01). Our results suggest that combining optical and
microwave modalities for analyzing breast tissue samples may
serve as a crosscheck and provide complementary information
about tissue composition.},
Key = {Lazebnik08}
}
@booklet{Zhu08,
Author = {C. F. Zhu and T. M. Breslin and J. Harter and N.
Ramanujam},
Title = {Model based and empirical spectral analysis for the
diagnosis of breast cancer},
Journal = {Optics Express},
Volume = {16},
Number = {19},
Pages = {14961 -- 14978},
Year = {2008},
Month = {September},
ISSN = {1094-4087},
Abstract = {We explored the use of both empirical (Partial Least
Squares, PLS) and Monte Carlo model based approaches for the
analysis of fluorescence and diffuse reflectance spectra
measured ex vivo from freshly excised breast tissues and for
the diagnosis of breast cancer. Features extracted using
both approaches, i.e. principal components (PCs) obtained
from empirical analysis or tissue properties obtained from
model based analysis, displayed statistically significant
difference between malignant and non-malignant tissues, and
can be used to discriminate breast malignancy with
comparable sensitivity and specificity of up to 90\%. The PC
scores of a subset of PCs also displayed significant
correlation with the tissue properties extracted from the
model based analysis, suggesting both approaches likely
probe the same sources of contrast in the tissue spectra
that discriminate between malignant and non-malignant breast
tissues but in different ways. (C) 2008 Optical Society of
America.},
Key = {Zhu08}
}
@booklet{Yu08a,
Author = {B. Yu and H. Fu and T. Bydlon and J. E. Bender and N.
Ramanujam},
Title = {Diffuse reflectance spectroscopy with a self-calibrating
fiber optic probe},
Journal = {Optics Letters},
Volume = {33},
Number = {16},
Pages = {1783 -- 1785},
Year = {2008},
Month = {August},
ISSN = {0146-9592},
Abstract = {Calibration of the diffuse reflectance spectrum for
instrument response and time-dependent fluctuation as well
as interdevice variations is complicated, time consuming,
and potentially inaccurate. We describe a novel fiber optic
probe with a real-time self-calibration capability that can
be used for tissue optical spectroscopy. The probe was
tested in a number of liquid phantoms over a relevant range
of tissue optical properties. Absorption and scattering
coefficients are extracted with an average absolute error
and standard deviation of 6.9\%+/- 7.2\% and 3.5\%+/- 1.5\%,
respectively. (C) 2008 Optical Society of
America.},
Key = {Yu08a}
}
@booklet{Zhu08a,
Author = {C. F. Zhu and G. M. Palmer and T. M. Breslin and J. Harter and N. Ramanujam},
Title = {Diagnosis of breast cancer using fluorescence and diffuse
reflectance spectroscopy: a Monte-Carlo-model-based
approach},
Journal = {Journal Of Biomedical Optics},
Volume = {13},
Number = {3},
Year = {2008},
ISSN = {1083-3668},
Abstract = {We explore the use of Monte-Carlo-model-based approaches for
the analysis of fluorescence and diffuse reflectance spectra
measured ex vivo from breast tissues. These models are used
to extract the absorption, scattering, and fluorescence
properties of malignant and nonmalignant tissues and to
diagnose breast cancer based on these intrinsic tissue
properties. Absorption and scattering properties, including
beta-carotene concentration, total hemoglobin concentration,
hemoglobin saturation, and the mean reduced scattering
coefficient are derived from diffuse reflectance spectra
using a previously developed Monte Carlo model of diffuse
reflectance. A Monte Carlo model of fluorescence described
in an earlier manuscript was employed to retrieve the
intrinsic fluorescence spectra. The intrinsic fluorescence
spectra were decomposed into several contributing
components, which we attribute to endogenous fluorophores
that may present in breast tissues including collagen, NADH,
and retinol/vitamin A. The model-based approaches removes
any dependency on the instrument and probe geometry. The
relative fluorescence contributions of individual
fluorescing components, as well as P-carotene concentration,
hemoglobin saturation, and the mean reduced scattering
coefficient display statistically significant differences
between malignant and adipose breast tissues. The hemoglobin
saturation and the reduced scattering coefficient display
statistically significant differences between malignant and
fibrous/benign breast tissues. A linear support vector
machine classification using (1) fluorescence properties
alone, (2) absorption and scattering properties alone, and
(3) the combination of all tissue properties achieves
comparable classification accuracies of 81 to 84\% in
sensitivity and 75 to 89\% in specificity for discriminating
malignant from nonmalignant breast tissues, suggesting each
set of tissue properties are diagnostically useful for the
discrimination of breast malignancy. (C) 2008 Society of
Photo-Optical Instrumentation Engineers.},
Key = {Zhu08a}
}
@booklet{Palmer08,
Author = {G. M. Palmer and N. Ramanujam},
Title = {Monte-Carlo-based model for the extraction of intrinsic
fluorescence from turbid media},
Journal = {Journal Of Biomedical Optics},
Volume = {13},
Number = {2},
Year = {2008},
ISSN = {1083-3668},
Abstract = {A Monte-Carlo-based model of fluorescence is developed that
is capable of extracting the intrinsic fluorescence
properties of tissue, which are independent of the
absorption and scattering properties of tissue. This model
is flexible in its applicability to different
illumination-collection geometries and is also valid for a
wide range of optical properties, representative of tissue
in the UV-visible spectrum. This is potentially useful in a
variety of biomedical applications, including cancer
diagnostics and monitoring the physiological response to
therapy. The model is validated using phantoms composed of
hemoglobin (absorber), polystyrene spheres (scatterer), and
furan-2 (fluorophore). It is found that this model is able
to retrieve the intrinsic fluorescence spectra of the tissue
phantoms and recover the intrinsic fluorescence intensity of
furan within the phantoms to within a mean error of less
than 10\%. (C) 2008 Society of Photo-Optical Instrumentation
Engineers.},
Key = {Palmer08}
}
@booklet{Brown07,
Author = {J. Q. Brown and L. G. Wilke and S. Kennedy and G. M. Palmer and J. Geradts and N. Ramanujam},
Title = {Intraoperative in vivo reflectance spectroscopy for
discrimination of normal, benign, and malignant breast
tissues},
Journal = {Breast Cancer Research And Treatment},
Volume = {106},
Pages = {S209 -- S210},
Year = {2007},
Month = {December},
ISSN = {0167-6806},
Key = {Brown07}
}
@booklet{Skala07,
Author = {M. C. Skala and K. M. Riching and A. Gendron-fitzpatrick and J. Eickhoff and K. W. Eliceiri and J. G. White and N.
Ramanujam},
Title = {In vivo multiphoton microscopy of NADH and FAD redox states,
fluorescence lifetimes, and cellular morphology in
precancerous epithelia},
Journal = {Proceedings Of The National Academy Of Sciences Of The
United States Of America},
Volume = {104},
Number = {49},
Pages = {19494 -- 19499},
Year = {2007},
Month = {December},
ISSN = {0027-8424},
Abstract = {Metabolic imaging of the relative amounts of reduced NADH
and FAD and the microenvironment of these metabolic electron
carriers can be used to noninvasively monitor changes in
metabolism, which is one of the hallmarks of carcinogenesis.
This study combines cellular redox ratio, NADH and FAD
lifetime, and subcellular morphology imaging in three
dimensions to identify intrinsic sources of metabolic and
structural contrast in vivo at the earliest stages of cancer
development. There was a significant (P $<$ 0.05) increase
in the nuclear to cytoplasmic ratio (NCR) with depth within
the epithelium in normal tissues; however, there was no
significant change in NCR with depth in precancerous
tissues. The redox ratio significantly decreased in the less
differentiated basal epithelial cells compared with the more
mature cells in the superficial layer of the normal
stratified squamous epithelium, indicating an increase in
metabolic activity in cells with increased NCR. However, the
redox ratio was not significantly different between the
superficial and basal cells in precancerous tissues. A
significant decrease was observed in the contribution and
lifetime of protein-bound NADH (averaged over the entire
epithelium) in both low- and high-grade epithelial
precancers compared with normal epithelial tissues. In
addition, a significant increase in the protein-bound FAD
lifetime and a decrease in the contribution of protein-bound
FAD are observed in high-grade precancers only. Increased
intracellular variability in the redox ratio, NADH, and FAD
fluorescence lifetimes were observed in precancerous cells
compared with normal cells.},
Key = {Skala07}
}
@booklet{Palmer07,
Author = {G. M. Palmer and N. Ramanujam},
Title = {Monte Carlo-based inverse model for calculating tissue
optical properties. Part I: Theory and validation on
synthetic phantoms (vol 45, pg 1062, 2006)},
Journal = {Applied Optics},
Volume = {46},
Number = {27},
Pages = {6847 -- 6847},
Year = {2007},
Month = {September},
ISSN = {0003-6935},
Key = {Palmer07}
}
@booklet{Palmer07a,
Author = {G. M. Palmer and N. Ramanujam},
Title = {Use of genetic algorithms to optimize fiber optic probe
design for the extraction of tissue optical
properties},
Journal = {Ieee Transactions On Biomedical Engineering},
Volume = {54},
Number = {8},
Pages = {1533 -- 1535},
Year = {2007},
Month = {August},
ISSN = {0018-9294},
Abstract = {This paper outlines a framework by which the optimal
illumination/collection geometry can be identified for a
particular biomedical application. In this paper, this
framework was used to identify the optimal probe geometry
for the accurate determination of tissue optical properties
representative of that in the ultraviolet-visible (UV-VIS)
spectral range. An optimal probe geometry was identified
which consisted of a single illumination and two collection
fibers, one of which is insensitive to changes in scattering
properties, and the other is insensitive to changes in the
attenuation coefficient. Using this probe geometry in
conjunction with a neural network algorithm, the optical
properties could be extracted with root-mean-square errors
of 0.30 cm(-1) for the reduced scattering coefficient
(tested range of 3-40 cm(-1)), and 0.41 cm(-1) for the
absorption coefficient (tested range of 0-80
cm(-1)).},
Key = {Palmer07a}
}
@booklet{Yu07,
Author = {B. Yu and E. S. Burnside and G. A. Sisney and J. M. Harter and C. Zhu and A. H. Dhalla and N. Ramanujam},
Title = {Feasibility of near-infrared diffuse optical spectroscopy on
patients undergoing image-guided core-needle
biopsy},
Journal = {Optics Express},
Volume = {15},
Number = {12},
Pages = {7335 -- 7350},
Year = {2007},
Month = {June},
ISSN = {1094-4087},
Abstract = {We describe a side-firing fiber optic sensor based on
near-infrared spectroscopy for guiding core needle biopsy
diagnosis of breast cancer. The sensor is composed of three
side firing optical fibers (two source fibers and one
detection fiber), providing two source-detector separations.
The entire assembly is inserted into a core biopsy needle,
allowing for sampling to occur at the biopsy site. A
multi-wavelength frequency-domain near-infrared instrument
is used to collect diffuse reflectance in the breast tissue
through an aperture on the biopsy needle before the tissue
is removed for histology. Preliminary in vivo measurements
performed on 10 normal or benign breast tissues from 5 women
undergoing stereo- or ultrasound-guided core needle biopsy
show the ability of the system to determine tissue optical
properties and constituent concentrations, which are
correlated with breast tissue composition derived from
histopathology.},
Key = {Yu07}
}
@booklet{Skala07a,
Author = {M. C. Skala and G. M. Palmer and K. M. Vrotsos and A.
Gendron-fitzpatrick and N. Ramanujam},
Title = {Comparison of a physical model and principal component
analysis for the diagnosis of epithelial neoplasias in vivo
using diffuse reflectance spectroscopy},
Journal = {Optics Express},
Volume = {15},
Number = {12},
Pages = {7863 -- 7875},
Year = {2007},
Month = {June},
ISSN = {1094-4087},
Abstract = {We explored the use of diffuse reflectance spectroscopy in
the ultraviolet-visible ( UV-VIS) spectrum for the diagnosis
of epithelial pre-cancers and cancers in vivo. A physical
model ( Monte Carlo inverse model) and an empirical model (
principal component analysis, ( PCA)) based approach were
compared for extracting diagnostic features from diffuse
reflectance spectra measured in vivo from the dimethylbenz[
a] anthracene-treated hamster cheek pouch model of oral
carcinogenesis. These diagnostic features were input into a
support vector machine algorithm to classify each tissue
sample as normal ( n= 10) or neoplastic ( dysplasia to
carcinoma, n= 10) and cross-validated using a leave one out
method. There was a statistically significant decrease in
the absorption and reduced scattering coefficient at 460 nm
in neoplastic compared to normal tissues, and these two
features provided 90\% classification accuracy. The first
two principal components extracted from PCA provided a
classification accuracy of 95\%. The first principal
component was highly correlated with the wavelength-averaged
reduced scattering coefficient. Although both methods show
similar classification accuracy, the physical model provides
insight into the physiological and structural features that
discriminate between normal and neoplastic tissues and does
not require a priori, a representative set of spectral data
from which to derive the principal components. (c) 2007
Optical Society.},
Key = {Skala07a}
}
@booklet{Liu07,
Author = {Q. Liu and N. Ramanujam},
Title = {Scaling method for fast Monte Carlo simulation of diffuse
reflectance spectra from multilayered turbid
media},
Journal = {Journal Of The Optical Society Of America A-optics Image
Science And Vision},
Volume = {24},
Number = {4},
Pages = {1011 -- 1025},
Year = {2007},
Month = {April},
ISSN = {1084-7529},
Abstract = {A scaling Monte Carlo method has been developed to calculate
diffuse reflectance from multilayered media with a wide
range of optical properties in the ultraviolet-visible
wavelength range. This multilayered scaling method employs
the photon trajectory information generated from a single
baseline Monte Carlo simulation of a homogeneous medium to
scale the exit distance and exit weight of photons for a new
set of optical properties in the multilayered medium. The
scaling method is particularly suited to simulating diffuse
reflectance spectra or creating a Monte Carlo database to
extract optical properties of layered media, both of which
are demonstrated in this paper. Particularly, it was found
that the root-mean-square error (RMSE) between scaled
diffuse reflectance, for which the anisotropy factor and
refractive index in the baseline simulation were,
respectively, 0.9 and 1.338, and independently simulated
diffuse reflectance was less than or equal to 5\% for
source-detector separations from 200 to 1500 mu m when the
anisotropy factor of the top layer in a two-layered
epithelial tissue model was varied from 0.8 to 0.99; in
contrast, the RMSE was always less than 5\% for all
separations (from 0 to 1500 mu m) when the anisotropy factor
of the bottom layer was varied from 0.7 to 0.99. When the
refractive index of either layer in the two-layered tissue
model was varied from 1.3 to 1.4, the RMSE was less than
10\%. The scaling method can reduce computation time by more
than 2 orders of magnitude compared with independent Monte
Carlo simulations. (c) 2007 Optical Society of
America.},
Key = {Liu07}
}
@article{fds71324,
Author = {Yu B and Burnside Rollins E and Sisney GA and Harter JM and Zhu C and Dhalla AH and Ramanujam N},
Title = {Feasibility of Near-Infrared Diffuse Optical Spectroscopy on
Patients Undergoing Image-Guided Core-Needle
Biopsy},
Journal = {Optics Express},
Volume = {15},
Number = {12},
Pages = {7335-50},
Year = {2007},
Key = {fds71324}
}
@article{fds71325,
Author = {Skala MC and Riching KM and Bird DK and Gendron-Fitzpatrick A and Eickhoff J and Eliceiri KW and Keely PJ and Ramanujam
N},
Title = {In vivo Multiphoton Fluorescence Lifetime Imaging of
Protein-bound and Free NADH in Normal and Pre-cancerous
Epithelia},
Journal = {Journal of Biomedical Optics},
Volume = {12},
Number = {2},
Pages = {024014},
Year = {2007},
Key = {fds71325}
}
@article{fds62316,
Author = {Skala MC and Riching KM and Gendron-Fitzpatrick A and Eliceiri KW and Ramanujam N},
Title = {In vivo multiphoton microscopy of metabolic
oxidation-reduction states and fluorescence lifetimes in
normal and pre-cancerous epithelia},
Journal = {Proc Nat Acad Sci},
Year = {2007},
Key = {fds62316}
}
@article{fds62333,
Author = {Skala MC and Palmer GM and Vrotsos KM and Gendron-Fitzpatrick A and Ramanujam N.},
Title = {Comparison of a Monte Carlo based physical model and
principal component analysis for the diagnosis of normal and
neoplastic epithelial tissues in vivo using diffuse
reflectance spectroscopy.},
Journal = {Optics Express},
Volume = {15},
Number = {12},
Pages = {7863-7875},
Year = {2007},
Key = {fds62333}
}
@article{9354800,
Author = {Quan Liu and Ramanujam, N.},
Title = {Scaling method for fast Monte Carlo simulation of diffuse
reflectance spectra from multilayered turbid
media},
Journal = {J. Opt. Soc. Am. A, Opt. Image Sci. Vis.
(USA)},
Volume = {24},
Number = {4},
Pages = {1011 - 25},
Year = {2007},
url = {http://dx.doi.org/10.1364/JOSAA.24.001011},
Keywords = {anisotropic media;bio-optics;biological tissues;mean square
error methods;Monte Carlo methods;photoreflectance;refractive
index;ultraviolet spectroscopy;visible spectroscopy;},
Abstract = {A scaling Monte Carlo method has been developed to calculate
diffuse reflectance from multilayered media with a wide
range of optical properties in the ultraviolet-visible
wavelength range. This multilayered scaling method employs
the photon trajectory information generated from a single
baseline Monte Carlo simulation of a homogeneous medium to
scale the exit distance and exit weight of photons for a new
set of optical properties in the multilayered medium. The
scaling method is particularly suited to simulating diffuse
reflectance spectra or creating a Monte Carlo database to
extract optical properties of layered media, both of which
are demonstrated in this paper. Particularly, it was found
that the root-mean-square error (RMSE) between scaled
diffuse reflectance, for which the anisotropy factor and
refractive index in the baseline simulation were,
respectively, 0.9 and 1.338, and independently simulated
diffuse reflectance was less than or equal to 5% for
source-detector separations from 200 to 1500 μm when the
anisotropy factor of the top layer in a two-layered
epithelial tissue model was varied from 0.8 to 0.99; in
contrast, the RMSE was always less than 5% for all
separations (from 0 to 1500 μm) when the anisotropy
factor of the bottom layer was varied from 0.7 to 0.99. When
the refractive index of either layer in the two-layered
tissue model was varied from 1.3 to 1.4, the RMSE was less
than 10%. The scaling method can reduce computation time by
more than 2 orders of magnitude compared with independent
Monte Carlo simulations},
Key = {9354800}
}
@booklet{Skala07b,
Author = {M. C. Skala and K. M. Riching and D. K. Bird and A.
Gendron-fitzpatrick and J. Eickhoff and K. W. Eliceiri and P. J. Keely and N. Ramanujam},
Title = {In vivo multiphoton fluorescence lifetime imaging of
protein-bound and free nicotinamide adenine dinucleotide in
normal and precancerous epithelia},
Journal = {Journal Of Biomedical Optics},
Volume = {12},
Number = {2},
Year = {2007},
ISSN = {1083-3668},
Abstract = {Multiphoton fluorescence lifetime imaging microscopy (FLIM)
is a noninvasive, cellular resolution, 3-D functional
imaging technique. We investigate the potential for in vivo
precancer diagnosis with metabolic imaging via multiphoton
FLIM of the endogenous metabolic cofactor nicotinamide
adenine dinucleotide (NADH). The dimethylbenz [alpha]
anthracene (DMBA)-treated hamster cheek pouch model of oral
carcinogenesis and MCF10A cell monolayers are imaged using
multiphoton FLIM at 780-nm excitation. The cytoplasm of
normal hamster cheek pouch epithelial cells has short (0.29
+/- 0.03 ns) and long lifetime components (2.03 +/- 0.06
ns), attributed to free and protein-bound NADH,
respectively. Low-grade precancers (mild to moderate
dysplasia) and high-grade precancers (severe dysplasia and
carcinoma in situ) are discriminated from normal tissues by
their decreased protein-bound NADH lifetime (p $<$ 0.05).
Inhibition of cellular glycolysis and oxidative
phosphorylation in cell monolayers produces an increase and
decrease, respectively, in the protein-bound NADH lifetime
(p $<$ 0.05). Results indicate that the decrease in
protein-bound NADH lifetime with dysplasia is due to a shift
from oxidative phosphorylation to glycolysis, consistent
with the predictions of neoplastic metabolism. We
demonstrate that multiphoton FLIM is a powerful tool for the
noninvasive characterization and detection of epithelial
precancers in vivo. (C) 2007 Society of Photo-Optical
Instrumentation Engineers.},
Key = {Skala07b}
}
@booklet{Millon06,
Author = {S. R. Millon and K. M. Roldan-perez and K. M. Riching and G.
M. Palmer and N. Ramanujam},
Title = {Effect of optical clearing agents on the in vivo optical
properties of squamous epithelial tissue},
Journal = {Lasers In Surgery And Medicine},
Volume = {38},
Number = {10},
Pages = {920 -- 927},
Year = {2006},
Month = {December},
ISSN = {0196-8092},
Abstract = {Background and Objectives: Optical clearing agents (OCAs)
have previously been shown to increase depth penetration
within turbid tissue ex vivo. This paper quantifies tissue
optical properties of the hamster cheek pouch model in order
to provide a means to assess the effect of OCAs
quantitatively in vivo. Study Design/Materials and Methods:
Diffuse reflectance spectra were obtained from both cheeks
of 12 hamsters before and after immersion in dimethyl
sulfoxide (DMSO), glycerol or a phosphate buffer saline
(PBS) control for 20 minutes. A Monte Carlo model was then
utilized to derive the wavelength dependent reduced
scattering and absorption coefficients. Results: DMSO caused
a statistically significant decrease in the absorption and
reduced scattering coefficients derived by the model.
Glycerol caused a statistically significant increase in the
wavelength dependent absorption coefficient, but no
statistically significant changes in the reduced scattering
coefficient. Conclusions: DMSO and glycerol act upon tissues
differently as reflected by the tissue optical properties,
implying that not all OCAs are equally effective in
optically clearing tissues.},
Key = {Millon06}
}
@booklet{Zhu06,
Author = {C. F. Zhu and G. M. Palmer and T. M. Breslin and J. Harter and N. Ramanujam},
Title = {Diagnosis of breast cancer using diffuse reflectance
spectroscopy: Comparison of a Monte Carlo versus partial
least squares analysis based feature extraction
technique},
Journal = {Lasers In Surgery And Medicine},
Volume = {38},
Number = {7},
Pages = {714 -- 724},
Year = {2006},
Month = {August},
ISSN = {0196-8092},
Abstract = {Background and Objective: We explored the use of diffuse
reflectance spectroscopy in the ultraviolet-visible
(U-V-VIS) spectrum for the diagnosis of breast cancer. A
physical model (Monte Carlo inverse model) and an empirical
model (partial least squares analysis) based approach, were
compared for extracting diagnostic features from the diffuse
reflectance spectra. Study Design/Methods: The physical
model and the empirical model were employed to extract
features from diffuse reflectance spectra measured from
freshly excised breast tissues. A subset of extracted
features obtained using each method showed statistically
significant differences between malignant and non-malignant
breast tissues. These features were separately input to a
support vector machine (SVM) algorithm to classify each
tissue sample as malignant or non-malignant. Results and
Conclusions: The features extracted from the Monte Carlo
based analysis were hemoglobin saturation, total hemoglobin
concentration, beta-carotene concentration and the mean
(wavelength averaged) reduced scattering coefficient.
Beta-carotene concentration was positively correlated and
the mean reduced scattering coefficient was negatively
correlated with percent adipose tissue content in normal
breast tissues. In addition, there was a statistically
significant decrease in the beta-carotene concentration and
hemoglobin saturation, and a statistically significant
increase in the mean reduced scattering coefficient in
malignant tissues compared to non-malignant tissues. The
features extracted from the partial least squares analysis
were a set of principal components. A subset of principal
components showed that the diffuse reflectance spectra of
malignant breast tissues displayed an increased intensity
over wavelength range of 440-510 nm and a decreased
intensity over wavelength range of 510-600 nm, relative to
that of non-malignant breast tissues. The diagnostic
performance of the classification algorithms based on both
feature extraction techniques yielded similar sensitivities
and specificities of approximately 80\% for discriminating
between malignant and nonmalignant breast tissues. While
both methods yielded similar classification accuracies, the
model based approach provided insight into the physiological
and structural features that discriminate between malignant
and nonmalignant breast tissues.},
Key = {Zhu06}
}
@booklet{Liu06,
Author = {Q. Liu and N. Ramanujam},
Title = {Sequential estimation of optical properties of a two-layered
epithelial tissue model from depth-resolved
ultraviolet-visible diffuse reflectance spectra},
Journal = {Applied Optics},
Volume = {45},
Number = {19},
Pages = {4776 -- 4790},
Year = {2006},
Month = {July},
ISSN = {0003-6935},
Abstract = {A method for estimating the optical properties of
two-layered media (such as squamous epithelial tissue) over
a range of wavelengths in the ultraviolet-visible spectrum
is proposed and tested with Monte Carlo modeling. The method
first used a fiber-optic probe with angled illumination and
the collection fibers placed at a small separation ($<$= 300
mu m) to restrict the transport of detected light to the top
layer. A Monte Carlo-based inverse model for a homogeneous
medium was employed to estimate the top layer optical
properties from the measured diffuse reflectance spectrum.
Then a flat-tip probe with a large source-detector
separation ($>$= 1000 mu m) was used to detect diffuse
reflectance preferentially from the bottom layer. A second
Monte Carlo-based inverse model for a two-layered medium was
applied to estimate the bottom layer optical properties, as
well as the top layer thickness, given that the top layer
optical properties have been estimated. The results of Monte
Carlo validation show that this method works well for an
epithelial tissue model with a top layer thickness ranging
from 200 to 500 mu m. For most thicknesses within this
range, the absorption coefficients were estimated to within
15\% of the true values, the reduced scattering coefficients
were estimated to within 20\% and the top layer thicknesses
were estimated to within 20\%. The application of a variance
reduction technique to the Monte Carlo modeling proved to be
effective in improving the accuracy with which the optical
properties are estimated. (c) 2006 Optical Society of
America.},
Key = {Liu06}
}
@booklet{Gill06,
Author = {E. M. Gill and C. A. Ivarie and K. W. Eliceiri and N.
Ramanujam and J. G. White and B. L. Allen-hoffmann},
Title = {Imaging human stratified squamous epithelia using nonlinear
optical microscopy},
Journal = {Journal Of Investigative Dermatology},
Volume = {126},
Year = {2006},
Month = {April},
ISSN = {0022-202X},
Key = {Gill06}
}
@booklet{Palmer06,
Author = {G. M. Palmer and N. Ramanujam},
Title = {Monte Carlo-based inverse model for calculating tissue
optical properties. Part I: Theory and validation on
synthetic phantoms},
Journal = {Applied Optics},
Volume = {45},
Number = {5},
Pages = {1062 -- 1071},
Year = {2006},
Month = {February},
ISSN = {0003-6935},
Abstract = {A flexible and fast Monte Carlo-based model of diffuse
reflectance has been developed for the extraction of the
absorption and scattering properties of turbid media, such
as human tissues. This method is valid for a wide range of
optical properties and is easily adaptable to existing probe
geometries, provided a single phantom calibration
measurement is made. A condensed Monte Carlo method was used
to speed up the for-ward simulations. This model was
validated by use of two sets of liquid-tissue phantoms
containing Nigrosin or hemoglobin as absorbers and
polystyrene spheres as scatterers. The phantoms had a wide
range of absorption (0-20 cm(-1)) and reduced scattering
coefficients (7-33 cm(-1)). Mie theory and a
spectrophotometer were used to determine the absorption and
reduced scattering coefficients of the phantoms. The diffuse
reflectance spectra of the phantoms were measured over a
wavelength range of 350-850 nm. It was found that optical
properties could be extracted from the experimentally
measured diffuse reflectance spectra with an average error
of 3\% or less for phantoms containing hemoglobin and 12\%
or less for phantoms containing Nigrosin. (c) 2006 Optical
Society of America.},
Key = {Palmer06}
}
@booklet{Palmer06a,
Author = {G. M. Palmer and C. F. Zhu and T. M. Breslin and F. S. Xu and K. W. Gilchrist and N. Ramanujam},
Title = {Monte Carlo-based inverse model for calculating tissue
optical properties. Part II: Application to breast cancer
diagnosis},
Journal = {Applied Optics},
Volume = {45},
Number = {5},
Pages = {1072 -- 1078},
Year = {2006},
Month = {February},
ISSN = {0003-6935},
Abstract = {The Monte Carlo-based inverse model of diffuse reflectance
described in part I of this pair of companion papers was
applied to the diffuse reflectance spectra of a set of 17
malignant and 24 normal-benign ex vivo human breast tissue
samples. This model allows extraction of physically
meaningful tissue parameters, which include the
concentration of absorbers and the size and density of
scatterers present in tissue. It was assumed that intrinsic
absorption could be attributed to oxygenated and
deoxygenated hemoglobin and beta-carotene, that scattering
could be modeled by spheres of a uniform size distribution,
and that the refractive indices of the spheres and the
surrounding medium are known. The tissue diffuse reflectance
spectra were evaluated over a wavelength range of 400-600
nm. The extracted parameters that showed the statistically
most significant differences between malignant and
nonmalignant breast tissues were hemoglobin saturation and
the mean reduced scattering coefficient. Malignant tissues
showed decreased hemoglobin saturation and an increased mean
reduced scattering coefficient compared with nonmalignant
tissues. A support vector machine classification algorithm
was then used to classify a sample as malignant or
nonmalignant based on these two extracted parameters and
produced a cross-validated sensitivity and specificity of
82\% and 92\%, respectively. (c) 2006 Optical Society of
America.},
Key = {Palmer06a}
}
@booklet{Chiles06,
Author = {S. Chiles and K. Roldan-perez and K. Riching and G. Palmer and N. Ramanujam},
Title = {Effect of optical clearing agents on the optical properties
of squamous epithelial tissue},
Journal = {Lasers In Surgery And Medicine},
Year = {2006},
ISSN = {0196-8092},
Key = {Chiles06}
}
@article{9133480,
Author = {Quan Liu and Ramanujam, N.},
Title = {Sequential estimation of optical properties of a two-layered
epithelial tissue model from depth-resolved
ultraviolet-visible diffuse reflectance spectra},
Journal = {Appl. Opt. (USA)},
Volume = {45},
Number = {19},
Pages = {4776 - 90},
Year = {2006},
url = {http://dx.doi.org/10.1364/AO.45.004776},
Keywords = {absorption coefficients;bio-optics;biological
tissues;cancer;cellular biophysics;fibre optic sensors;Monte
Carlo methods;patient diagnosis;physiological
models;reflectivity;ultraviolet spectra;visible
spectra;},
Abstract = {A method for estimating the optical properties of
two-layered media (such as squamous epithelial tissue) over
a range of wavelengths in the ultraviolet-visible spectrum
is proposed and tested with Monte Carlo modeling. The method
first used a fiber-optic probe with angled illumination and
the collection fibers placed at a small separation (⩽300
μm) to restrict the transport of detected light to the
top layer. A Monte Carlo-based inverse model for a
homogeneous medium was employed to estimate the top layer
optical properties from the measured diffuse reflectance
spectrum. Then a flat-tip probe with a large source-detector
separation (⩾1000 μm) was used to detect diffuse
reflectance preferentially from the bottom layer. A second
Monte Carlo-based inverse model for a two-layered medium was
applied to estimate the bottom layer optical properties, as
well as the top layer thickness, given that the top layer
optical properties have been estimated. The results of Monte
Carlo validation show that this method works well for an
epithelial tissue model with a top layer thickness ranging
from 200 to 500 μm. For most thicknesses within this
range, the absorption coefficients were estimated to within
15% of the true values, the reduced scattering coefficients
were estimated to within 20% and the top layer thicknesses
were estimated to within 20%. The application of a variance
reduction technique to the Monte Carlo modeling proved to be
effective in improving the accuracy with which the optical
properties are estimated},
Key = {9133480}
}
@article{8915044,
Author = {Palmer, G.M. and Ramanujam, N.},
Title = {Monte Carlo-based inverse model for calculating tissue
optical properties. Part I: Theory and validation on
synthetic phantoms},
Journal = {Appl. Opt. (USA)},
Volume = {45},
Number = {5},
Pages = {1062 - 71},
Year = {2006},
url = {http://dx.doi.org/10.1364/AO.45.001062},
Keywords = {absorption coefficients;bio-optics;biological
tissues;calibration;light scattering;molecular
biophysics;Monte Carlo methods;phantoms;physiological
models;proteins;reflectivity;spectrophotometry;turbidity;},
Abstract = {A flexible and fast Monte Carlo-based model of diffuse
reflectance has been developed for the extraction of the
absorption and scattering properties of turbid media, such
as human tissues. This method is valid for a wide range of
optical properties and is easily adaptable to existing probe
geometries, provided a single phantom calibration
measurement is made. A condensed Monte Carlo method was used
to speed up the forward simulations. This model was
validated by use of two sets of liquid-tissue phantoms
containing Nigrosin or hemoglobin as absorbers and
polystyrene spheres as scatterers. The phantoms had a wide
range of absorption (0-20 cm<sup>-1</sup>) and reduced
scattering coefficients (7-33 cm<sup>-1</sup>). Mie theory
and a spectrophotometer were used to determine the
absorption and reduced scattering coefficients of the
phantoms. The diffuse reflectance spectra of the phantoms
were measured over a wavelength range of 350-850 nm. It was
found that optical properties could be extracted from the
experimentally measured diffuse reflectance spectra with an
average error of 3% or less for phantoms containing
hemoglobin and 12% or less for phantoms containing
Nigrosin},
Key = {8915044}
}
@article{8915045,
Author = {Palmer, G.M. and Changfang Zhu and Breslin, T.M. and Fushen
Xu and Gilchrist, K.W. and Ramanujam, N.},
Title = {Monte Carlo-based inverse model for calculating tissue
optical properties. Part II: Application to breast cancer
diagnosis},
Journal = {Appl. Opt. (USA)},
Volume = {45},
Number = {5},
Pages = {1072 - 8},
Year = {2006},
url = {http://dx.doi.org/10.1364/AO.45.001072},
Keywords = {bio-optics;biological organs;biological tissues;cancer;gynaecology;light
scattering;molecular biophysics;Monte Carlo
methods;oxygen;patient diagnosis;physiological
models;proteins;reflectivity;refractive index;support vector
machines;},
Abstract = {For Part I see ibid., Vol. 45, pp. 1062-71 (2006). The Monte
Carlo-based inverse model of diffuse reflectance described
in Part I of this pair of companion papers was applied to
the diffuse reflectance spectra of a set of 17 malignant and
24 normal-benign ex vivo human breast tissue samples. This
model allows extraction of physically meaningful tissue
parameters, which include the concentration of absorbers and
the size and density of scatterers present in tissue. It was
assumed that intrinsic absorption could be attributed to
oxygenated and deoxygenated hemoglobin and beta-carotene,
that scattering could be modeled by spheres of a uniform
size distribution, and that the refractive indices of the
spheres and the surrounding medium are known. The tissue
diffuse reflectance spectra were evaluated over a wavelength
range of 400-600 nm. The extracted parameters that showed
the statistically most significant differences between
malignant and nonmalignant breast tissues were hemoglobin
saturation and the mean reduced scattering coefficient.
Malignant tissues showed decreased hemoglobin saturation and
an increased mean reduced scattering coefficient compared
with nonmalignant tissues. A support vector machine
classification algorithm was then used to classify a sample
as malignant or nonmalignant based on these two extracted
parameters and produced a cross-validated sensitivity and
specificity of 82% and 92%, respectively},
Key = {8915045}
}
@article{8416441,
Author = {Changfang Zhu and Palmer, G.M. and Breslin, T.M. and Fushen
Xu and Ramanujam, N.},
Title = {Use of a multiseparation fiber optic probe for the optical
diagnosis of breast cancer},
Journal = {J. Biomed. Opt. (USA)},
Volume = {10},
Number = {2},
Pages = {24032 - 1},
Year = {2005},
url = {http://dx.doi.org/10.1117/1.1897398},
Keywords = {biomedical optical imaging;cancer;fibre optic
sensors;fluorescence spectroscopy;gynaecology;optical design
techniques;statistical analysis;tumours;ultraviolet
spectroscopy;visible spectroscopy;},
Abstract = {We explore the effects of the illumination and collection
geometry on optical spectroscopic diagnosis of breast
cancer. Fluorescence and diffuse reflectance spectroscopy in
the UV-visible spectral range are made with a
multiseparation probe at three illumination-collection
separations of 735, 980, and 1225 μm, respectively, from
13 malignant and 34 nonmalignant breast tissues. Statistical
analysis is carried out on two types of data inputs: (1) the
fluorescence and diffuse reflectance spectra recorded at
each of the three illumination-collection separations and
(2) the integrated fluorescence (at each excitation
wavelength) or diffuse reflectance over the entire spectrum
at all three illumination-collection separations. The
results show that using the integrated fluorescence
intensities recorded at a single excitation wavelength at
all three illumination-collection separations can
discriminate malignant from nonmalignant breast tissues with
similar classification accuracy to that using spectral data
measured at several excitation wavelengths with a single
illumination-collection separation. These findings have
significant implications with respect to the design of an
optical system for breast cancer diagnosis. Examining the
intensity attenuation at a single wavelength rather than
spectral intensities at multiple wavelengths can
significantly reduce the measurement and data processing
time in a clinical setting as well as the cost and
complexity of the optical system},
Key = {8416441}
}
@article{7772812,
Author = {Palmer, G.M. and Changfang Zhu and Breslin, T.M. and Fushen
Xu and Gilchrist, K.W. and Ramanujam, N.},
Title = {Comparison of multiexcitation fluorescence and diffuse
reflectance spectroscopy for the diagnosis of breast cancer
(March 2003)},
Journal = {IEEE Trans. Biomed. Eng. (USA)},
Volume = {50},
Number = {11},
Pages = {1233 - 42},
Year = {2003},
url = {http://dx.doi.org/10.1109/TBME.2003.818488},
Keywords = {bio-optics;biological organs;cancer;fluorescence
spectroscopy;gynaecology;learning automata;medical signal
processing;pattern classification;principal component
analysis;reflectivity;spectral analysis;tumours;ultraviolet
spectroscopy;},
Abstract = {Nonmalignant (n = 36) and malignant (n = 20) tissue samples
were obtained from breast cancer and breast reduction
surgeries. These tissues were characterized using multiple
excitation wavelength fluorescence spectroscopy and diffuse
reflectance spectroscopy in the ultraviolet-visible
wavelength range, immediately after excision. Spectra were
then analyzed using principal component analysis (PCA) as a
data reduction technique. PCA was performed on each
fluorescence spectrum, as well as on the diffuse reflectance
spectrum individually, to establish a set of principal
components for each spectrum. A Wilcoxon rank-sum test was
used to determine which principal components show
statistically significant differences between malignant and
nonmalignant tissues. Finally, a support vector machine
(SVM) algorithm was utilized to classify the samples based
on the diagnostically useful principal components.
Cross-validation of this nonparametric algorithm was carried
out to determine its classification accuracy in an unbiased
manner. Multiexcitation fluorescence spectroscopy was
successful in discriminating malignant and nonmalignant
tissues, with a sensitivity and specificity of 70% and 92%,
respectively. The sensitivity (30%) and specificity (78%) of
diffuse reflectance spectroscopy alone was significantly
lower. Combining fluorescence and diffuse reflectance
spectra did not improve the classification accuracy of an
algorithm based on fluorescence spectra alone. The
fluorescence excitation-emission wavelengths identified as
being diagnostic from the PCA-SVM algorithm suggest that the
important fluorophores for breast cancer diagnosis are most
likely tryptophan, NAD(P)H and flavoproteins},
Key = {7772812}
}
@article{03447706844,
Author = {Palmer, Gregory M. and Ramanujam, Nirmala},
Title = {Diagnosis of Breast Cancer Using Optical
Spectroscopy},
Journal = {Medical Laser Application},
Volume = {18},
Number = {3},
Pages = {233 - 248},
Year = {2003},
Keywords = {Tumors;Diagnosis;Fluorescence;Spectroscopic
analysis;},
Abstract = {Fluorescence and diffuse reflectance spectroscopy have shown
great promise in diagnosing cancer at a number of organ
sites, including the cervix, bronchus, and colon. Recent
research has also found that similar techniques, when
applied to the breast, can provide fast, accurate diagnosis
of breast cancer. An additional avenue of research has
focused on investigating the biological basis of
spectroscopic differences seen in tissue. This manuscript
serves as a review of these recent studies, as well as
providing an outline of future work yet to be accomplished
to further the use of these techniques as a clinical
tool.},
Key = {03447706844}
}
@article{7584693,
Author = {Changfang Zhu and Quan Liu and Ramanujam,
N.},
Title = {Effect of fiber optic probe geometry on depth-resolved
fluorescence measurements from epithelial tissues: a Monte
Carlo simulation},
Journal = {J. Biomed. Opt. (USA)},
Volume = {8},
Number = {2},
Pages = {237 - 47},
Year = {2003},
url = {http://dx.doi.org/10.1117/1.1559058},
Keywords = {biological tissues;fibre optic sensors;fluorescence;Monte
Carlo methods;physiological models;probes;},
Abstract = {Developing fiber optic probe geometries to selectively
measure fluorescence spectra from different sublayers within
human epithelial tissues will potentially improve the
endogenous fluorescence contrast between neoplastic and
nonneoplastic tissues. In this study, two basic fiber optic
probe geometries, which are called the variable aperture
(VA) and multidistance (MD) approaches, are compared for
depth-resolved fluorescence measurements from human cervical
epithelial tissues. The VA probe has completely overlapping
illumination and collection areas with variable diameters,
while the MD probe employs separate illumination and
collection fibers with a fixed separation between them.
Monte Carlo simulation results show that the total
fluorescence detected is significantly higher for the VA
probe geometry, while the probing depth is significantly
greater for the MD probe geometry. An important observation
is that the VA probe is more sensitive to the epithelial
layer, while the MD probe is more sensitive to the stromal
layer. The effect of other factors, including numerical
aperture (NA) and tissue optical properties on the
fluorescence measurements with VA and MD probe geometries,
are also evaluated. The total fluorescence detected with
both probe geometries significantly increases when the fiber
NA is changed from 0.22 to 0.37. The sensitivity to
different sublayers is found to be strongly dependent on the
tissue optical properties. The simulation results are used
to design a simple fiber optic probe that combines both the
VA and MD geometries to enable fluorescence measurements
from the different sublayers within human epithelial
tissues},
Key = {7584693}
}
@article{7584692,
Author = {Quan Liu and Changfang Zhu and Ramanujam,
N.},
Title = {Experimental validation of Monte Carlo modeling of
fluorescence in tissues in the UV-visible
spectrum},
Journal = {J. Biomed. Opt. (USA)},
Volume = {8},
Number = {2},
Pages = {223 - 36},
Year = {2003},
url = {http://dx.doi.org/10.1117/1.1559057},
Keywords = {absorption coefficients;biological tissues;digital
simulation;fibre optic sensors;fluorescence;light
scattering;Monte Carlo methods;phantoms;physiological
models;reflectivity;turbidity;},
Abstract = {The goal of the work is to experimentally verify Monte Carlo
modeling of fluorescence and diffuse reflectance
measurements in turbid, tissue phantom models. In
particular, two series of simulations and experiments, in
which one optical parameter (absorption or scattering
coefficient) is varied while the other is fixed, are carried
out to assess the effect of the absorption coefficient
(μ<sub>a</sub>) and scattering coefficient
(μ<sub>s</sub>) on the fluorescence and diffuse
reflectance measured from a turbid medium. Moreover,
simulations and experiments are carried out for several
fiber optic probe geometries that are designed to sample
small tissue volumes. Additionally, a group of conversion
expressions are derived to convert the optical properties
and fluorescence quantum yield measured from tissue phantoms
for use in Monte Carlo simulations. The conversions account
for the differences between the definitions of the
absorption coefficient and fluorescence quantum yield of
fluorophores in a tissue phantom model and those in a Monte
Carlo simulation. The results indicate that there is good
agreement between the simulated and experimentally measured
results in most cases. This dataset can serve as a
systematic validation of Monte Carlo modeling of fluorescent
light propagation in tissues. The simulations are carried
out for a wide range of absorption and scattering
coefficients as well as ratios of scattering coefficient to
absorption coefficient, and thus would be applicable to
tissue optical properties over a wide wavelength range
(UV-visible/near infrared). The fiber optic probe geometries
that are modeled in this study include those commonly used
for measuring fluorescence from tissues in
practice},
Key = {7584692}
}
@article{7244180,
Author = {Liu Quan and Ramanujam, N.},
Title = {Relationship between depth of a target in a turbid medium
and fluorescence measured by a variable-aperture
method},
Journal = {Opt. Lett. (USA)},
Volume = {27},
Number = {2},
Pages = {104 - 6},
Year = {2002},
Keywords = {biological tissues;bioluminescence;biomedical
imaging;cancer;fluorescence;Monte Carlo methods;},
Abstract = {The relationship between the depth of a target in a turbid
medium and the fluorescence ratio profile measured by use of
illumination and collection apertures with variable
diameters and the same optical path is shown. The forward
problem was studied by Monte Carlo simulations of the
propagation of fluorescent light through a theoretical model
of a biologically relevant system for a range of aperture
diameters. The curve of the fluorescence ratio as a function
of the aperture diameter is characterized by a
maximum/minimum point whose position shifts linearly with
the depth of the target. Furthermore, the position of the
maximum/minimum is observed to be insensitive to variations
in the fluorescence efficiency and to the optical properties
of the target layer or the entire medium},
Key = {7244180}
}
@article{7153066,
Author = {Yueqing Gu and Zhiyu Qian and Jinxian Chen and Blessington,
D. and Ramanujam, N. and Chance, B.},
Title = {High-resolution three-dimensional scanning optical image
system for intrinsic and extrinsic contrast agents in
tissue},
Journal = {Rev. Sci. Instrum. (USA)},
Volume = {73},
Number = {1},
Pages = {172 - 8},
Year = {2002},
url = {http://dx.doi.org/10.1063/1.1424907},
Keywords = {biochemistry;biological tissues;bioluminescence;biomedical
imaging;blood vessels;fluorescence;liver;medical image
processing;proteins;tumours;visible spectroscopy;},
Abstract = {This article presents the theory and development of a
three-dimensional (3D) imaging instrument capable of
determining the biochemical properties of tissue by
measuring the absorption or fluorescence of different
intrinsic and extrinsic agents simultaneously. A bifurcated
optical fiber bundle, serving to deliver the excitation
light and collect the emission or reflection light, scans
over the flat tissue surface retrieving optical signals in
each pixel. Two-dimensional (2D) images of a series of
subsequent sections are obtained after signal conversion and
processing to yield a 3D image. Manipulation of the scanning
step and diameter size of the fibers within the bundle, the
spatial resolution of the instrument attains a maximum of 40
× 40 × 10 μm<sup>3</sup>. The wavelength
range is extended from ultraviolet to the near infrared
(NIR) through specialized optical design, typically employed
for the NIR extrinsic contrast agents study. The instrument
is most applicable in situations involving the measurement
of fluorescence or absorption at any specific wavelength
within the spectrum range. Flavoprotein and nicotinamide
adeine dinucleotide are the two typical intrinsic agents
indicating the oxidization and reduction status of the
tissue sample, with their fluorescence detected at
wavelengths of 540 and 440 nm, respectively. Oxy and deoxy
hemoglobin are two other significant intrinsic agents for
evaluating the blood oxygenation saturation by recording
their absorptions at two different wavelengths of 577 and
546 nm. These intrinsic agents were measured in this study
for comparison of biochemical properties of rat liver in
different gas inhalation treatments. Indocyanine green, a
NIR extrinsic contrast agent measured at wavelengths of 780
nm/830 nm as excitation/emission can indicate blood pooling
by displaying the distribution of blood vessels within a 9 L
tumor. The advantage of high sensitivity, spatial
resolution, and broad applied potentiality were demonstrated
by the instrument during these experiments},
Key = {7153066}
}
@article{01446711344,
Author = {Cai, Y. and Ramanujam, N. and Morris, J.M. and Adali, T. and Lenner, G. and Puc, A.B. and Pilipetskii,
A.},
Title = {Performance limit of forward error correction codes in
optical fiber communications},
Journal = {Conference on Optical Fiber Communication, Technical Digest
Series},
Volume = {54},
Number = {2},
Pages = {2 - 1},
Address = {Anaheim, CA},
Year = {2001},
Keywords = {Optical communication;Error correction;Light
amplifiers;Statistical methods;Approximation
theory;Probability;},
Abstract = {We investigate performance limits of forward error
correction codes in optically-amplified fiber channels with
asymmetric channel statistics. We show that the binary
symmetric channel approximation underestimates the maximum
coding gain achievable in fiber communications.},
Key = {01446711344}
}
@article{04328303793,
Author = {Ramanujam, Nirmala and Richards-Kortum, Rebecca and Thomsen,
Sharon and Mahadevan-Jansen, Anita and Follen, Michele and Chance, Britton},
Title = {Low temperature fluorescence imaging of freeze-trapped human
cervical tissues},
Journal = {Optics Express},
Volume = {8},
Number = {6},
Pages = {335 - 343},
Year = {2001},
Keywords = {Low temperature effects;Freezing;Tissue;Plastics;Microstructure;Spectroscopic
analysis;},
Abstract = {We characterized the fluorescence intensity distribution
within the epithelia and stroma of frozen human cervical
tissues at the following excitation-emission wavelength
pairs: 440, 525 nm and 365, 460 nm. The intensities at both
excitation-emission wavelength pairs are significantly lower
in the epithelia of severely dysplastic tissues, relative to
that in normal and inflammatory tissues. Furthermore, there
are small differences in (1) the epithelial intensity of
severe dysplasia and mild dysplasia at 440, 525 nm and (2)
the stromal intensity of inflammatory and severely
dysplastic tissues at 365, 460 nm. A comparison of the ratio
of intensities at 440, 525 nm and 365, 460 nm between the
epithelia of each tissue type indicates that this ratio is
lowest in severely dysplastic tissues. It is interesting to
note that the epithelial and stromal intensities are
comparable at 365, 460 nm; however, at 440, 525 nm, the
epithelial intensity is more than a factor of two less that
that of the stroma for all tissue types. © 2001 Optical
Society of America.},
Key = {04328303793}
}
@article{7269715,
Author = {Vishnoi, G. and Choe, R. and Ramanujam, N. and Rode, M.E. and Chance, B.},
Title = {On-line monitoring of oxy- and deoxy-hemoglobin using near
infra-red spectroscopic techniques},
Journal = {Proc. SPIE - Int. Soc. Opt. Eng. (USA)},
Volume = {4417},
Pages = {493 - 9},
Address = {Calcutta, India},
Year = {2001},
url = {http://dx.doi.org/10.1117/12.441341},
Keywords = {bio-optics;blood;infrared spectroscopy;light
scattering;oximetry;patient monitoring;proteins;real-time
systems;spectrochemical analysis;turbidity;},
Abstract = {Describes the design, development and characterization of a
dual wavelength, phase modulated device in the near infrared
region which can be used for real time monitoring of oxy-
and deoxy-hemoglobin. The device measures amplitude and
phase which can be employed in the diffusion equation for a
homogeneous semi-infinite medium to obtain the concentration
of oxy- and deoxy-hemoglobin of the sample},
Key = {7269715}
}
@article{6926664,
Author = {Ramanujam, N. and Richards-Kortum, R. and Thomsen, S. and Mahadevan-Jansen, A. and Follen, M. and Chance,
B.},
Title = {Low temperature fluorescence imaging of freeze-trapped human
cervical tissues},
Journal = {Opt. Express (USA)},
Volume = {8},
Number = {6},
Year = {2001},
Keywords = {biological tissues;biomedical imaging;cancer;cryogenics;fluorescence;spectral
line intensity;},
Abstract = {We characterized the fluorescence intensity distribution
within the epithelia and stroma of frozen human cervical
tissues at the following excitation-emission wavelength
pairs: 440, 525 nm and 365, 460 nm. The intensities at both
excitation-emission wavelength pairs are significantly lower
in the epithelia of severely dysplastic tissues, relative to
that in normal and inflammatory tissues. Furthermore, there
are small differences in (I) the epithelial intensity of
severe dysplasia and mild dysplasia at 440, 525 nm and (2)
the stromal intensity of inflammatory and severely
dysplastic tissues at 365, 460 nm. A comparison of the ratio
of intensities at 440, 525 nm and 365, 460 nm between the
epithelia of each tissue type indicates that this ratio is
lowest in severely dysplastic tissues. It is interesting to
note that the epithelial and stromal intensities are
comparable at 365, 460 nm; however, at 440, 525 nm, the
epithelial intensity is more than a factor of two less that
that of the stroma for all tissue types},
Key = {6926664}
}
@article{6728179,
Author = {Kidorf, H. and Ramanujam, N. and Hayee, I. and Nissov, M. and Cai, J.-X. and Pedersen, B. and Puc, A. and Rivers,
C.},
Title = {Performance improvement in high capacity, ultra-long
distance, WDM systems using forward error correction
codes},
Journal = {Optical Fiber Communication Conference. Technical Digest
Postconference Edition. Trends in Optics and Photonics
Vol.37 (IEEE Cat. No. 00CH37079)},
Volume = {vol.3},
Pages = {274 - 6},
Address = {Baltimore, MD, USA},
Year = {2000},
url = {http://dx.doi.org/10.1109/OFC.2000.868589},
Keywords = {forward error correction;Monte Carlo methods;optical fibre
communication;Reed-Solomon codes;telecommunication
channels;wavelength division multiplexing;},
Abstract = {We present a performance study of a forward error correction
(FEC) code using theoretical models, Monte-Carlo computer
simulations, and a long-haul WDM transmission experiment.
With a 14% redundancy code, the Q-factor was increased by
6.2 dB for both linear and non-linear impairments},
Key = {6728179}
}
@article{7068360,
Author = {Ramanujam, N. and Lifeng Li and Burke, J.J.},
Title = {A novel design technique for mode control in multilayer
waveguides},
Journal = {Trends in Optics and Photonics. Integrated Photonics
Research. Vol.45. Technical Digest. Postconference
Edition},
Pages = {165 - 7},
Address = {Quebec, Que., Canada},
Year = {2000},
Keywords = {birefringence;integrated optics;lithium compounds;optical
design techniques;optical dispersion;optical harmonic
generation;optical multilayers;optical waveguide
theory;potassium compounds;titanium compounds;},
Abstract = {The phase shift upon reflection from interfaces can be used
to control propagation characteristics such as mode profile
and chromatic dispersion. We demonstrate this in the case of
efficient second harmonic generation in diffused channel
waveguides. It has been shown that SHG efficiency can be
increased by as much as 37 % and 78 % in KTP and
LiTaO<sub>3</sub> waveguides respectively, with
specially-designed overlays. This design technique can be
extended to compensation of birefringence-induced effects as
well},
Key = {7068360}
}
@article{6686566,
Author = {Jacques, S.L. and Ramanujam, N. and Vishnoi, G. and Choe, R. and Chance, B.},
Title = {Modeling photon transport in transabdominal fetal
oximetry},
Journal = {J. Biomed. Opt. (USA)},
Volume = {5},
Number = {3},
Pages = {277 - 82},
Year = {2000},
url = {http://dx.doi.org/10.1117/1.429996},
Keywords = {bio-optics;brain;obstetrics;oximetry;paediatrics;patient
monitoring;perturbation theory;},
Abstract = {The possibility of optical oximetry of the blood in the
fetal brain measured across the maternal abdomen just prior
to birth is under investigation. Such measurements could
detect fetal distress prior to birth and aid in the clinical
decision regarding Cesarean section. This paper uses a
perturbation method to model photon transport through an
8-cm-diam fetal brain located at a constant 2.5 cm below a
curved maternal abdominal surface with an air/tissue
boundary. In the simulation, a near-infrared light source
delivers light to the abdomen and a detector is positioned
up to 10 cm from the source along the arc of the abdominal
surface. The light transport [W/cm<sup>2</sup> fluence rate
per W incident power] collected at the 10 cm position is
T<sub>m</sub>=2.2×10<sup>-6</sup> cm<sup>-2</sup> if
the fetal brain has the same optical properties as the
mother and T<sub>f</sub>=1.0×10<sup>-6</sup>
cm<sup>-2</sup> for an optically perturbing fetal brain with
typical brain optical properties. The perturbation
P=(T<sub>f</sub>-T<sub>m</sub>)/T<sub>m</sub> is -53% due to
the fetal brain. The model illustrates the challenge and
feasibility of transabdominal oximetry of the fetal
brain},
Key = {6686566}
}
@article{6686550,
Author = {Vishnoi, G. and Hielscher, A.H. and Ramanujam, N. and Chance, B.},
Title = {Photon migration through fetal head in utero
using continuous wave, near-infrared spectroscopy:
development and evaluation of experimental and numerical
models},
Journal = {J. Biomed. Opt. (USA)},
Volume = {5},
Number = {2},
Pages = {163 - 72},
Year = {2000},
url = {http://dx.doi.org/10.1117/1.429983},
Keywords = {biomedical imaging;biomedical measurement;finite difference
methods;infrared spectroscopy;physiological
models;},
Abstract = {In this work experimental tissue phantoms and numerical
models were developed to estimate photon migration through
the fetal head <i>in</i> <i>utero</i>. The tissue phantoms
incorporate a fetal head within an amniotic fluid sac
surrounded by a maternal tissue layer. A continuous wave,
dual-wavelength (λ=760 and 850 nm) spectrometer was
employed to make near-infrared measurements on the tissue
phantoms for various source-detector separations, fetal-head
positions, and fetal-head optical properties. In addition,
numerical simulations of photon propagation were performed
with finite-difference algorithms that provide solutions to
the equation of radiative transfer as well as the diffusion
equation. The simulations were compared with measurements on
tissue phantoms to determine the best numerical model to
describe photon migration through the fetal head <i>in</i>
<i>utero</i>. Evaluation of the results indicates that
tissue phantoms in which the contact between fetal head and
uterine wall is uniform best simulates the fetal head
<i>in</i> <i>utero</i> for near-term pregnancies.
Furthermore, we found that maximum sensitivity to the head
can be achieved if the source of the probe is positioned
directly above the fetal head. By optimizing the
source-detector separation, the signal originating from
photons that have traveled through the fetal head can
drastically be increased},
Key = {6686550}
}
@article{6686545,
Author = {Ramanujam, N. and Vishnoi, G. and Hielscher, A. and Rode, M. and Forouzan, I. and Chance, B.},
Title = {Photon migration through fetal head in utero
using continuous wave, near infrared spectroscopy: clinical
and experimental model studies},
Journal = {J. Biomed. Opt. (USA)},
Volume = {5},
Number = {2},
Pages = {173 - 84},
Year = {2000},
url = {http://dx.doi.org/10.1117/1.429984},
Keywords = {bio-optics;biomedical measurement;infrared
spectroscopy;obstetrics;},
Abstract = {Near infrared (NIR) measurements were made from the maternal
abdomen (clinical studies) and laboratory tissue phantoms
(experimental studies) to gain insight into photon migration
through the fetal head <i>in</i> <i>utero</i>. Specifically,
a continuous wave spectrometer was modified and employed to
make NIR measurements at 760 and 850 nm, at a large (10 cm)
and small (2.5/4 cm) source-detector separation,
simultaneously, on the maternal abdomen, directly above the
fetal head. A total of 19 patients were evaluated, whose
average gestational age and fetal head depth, were 37 weeks
±3 and 2.25 cm ±0.7, respectively. At the
large source-detector separation, the photons are expected
to migrate through both the underlying maternal and fetal
tissues before being detected at the surface, while at the
short source-detector separation, the photons are expected
to migrate primarily through the superficial maternal
tissues before being detected. Second, similar NIR
measurements were made on laboratory tissue phantoms, with
variable optical properties and physical geometries. The
variable optical properties were obtained using different
concentrations of India ink and Intralipid in water, while
the variable physical geometries were realized by employing
glass containers of different shapes and sizes. Third, the
NIR measurements, which were made on the laboratory tissue
phantoms, were compared to the NIR measurements made on the
maternal abdomen to determine which tissue phantom best
simulates the photon migration path through the fetal head
<i>in</i> <i>utero</i>. The results of the comparison were
used to provide insight into the optical properties and
physical geometry of the maternal and fetal tissues in the
photon migration path},
Key = {6686545}
}
@article{6533237,
Author = {Natesan, S. and Ramanujam, N.},
Title = {Booster method for singularly-perturbed one-dimensional
reaction-diffusion Neumann problems},
Journal = {J. Optim. Theory Appl. (USA)},
Volume = {104},
Number = {1},
Pages = {175 - 94},
Year = {2000},
url = {http://dx.doi.org/10.1023/A:1004637024562},
Keywords = {approximation theory;boundary-value problems;differential
equations;finite difference methods;},
Abstract = {A numerical method for singularly-perturbed self-adjoint
boundary-value problems for second-order ordinary
differential equations subject to Neumann boundary
conditions is proposed. In this method (booster method), an
asymptotic approximation is incorporated into a
finite-difference scheme to improve the numerical solution.
Uniform error estimates are derived for this method when
implemented in known difference schemes. Numerical examples
are presented to illustrate the present method},
Key = {6533237}
}
@article{99020017723,
Author = {Yazdi, Youseph and Ramanujam, Nirmala and Lotan, Reuben and Mitchell, Michele Follen and Hittelman, Walter and Richards-Kortum, Rebecca},
Title = {Resonance Raman spectroscopy at 257 nm excitation of normal
and malignant cultured breast and cervical
cells},
Journal = {Applied Spectroscopy},
Volume = {53},
Number = {1},
Pages = {82 - 85},
Year = {1999},
url = {http://dx.doi.org/10.1366/0003702991945254},
Keywords = {Ultraviolet spectroscopy;Oncology;Gynecology;Biochemistry;Cell
culture;DNA;Laser applications;Spectrographs;Charge coupled
devices;Cytology;},
Abstract = {The sensitivity and selectivity of ultraviolet (UV)-excited
resonance Raman spectroscopy indicate that this technique
may be useful in studying certain biochemical changes in
cells, especially changes in DNA that occur during the
development of cancer. To determine whether this technique
can distinguish normal from malignant cells, UV resonance
Raman spectra at 257.26 nm excitation of suspensions of
normal and malignant cultured breast and cervical samples
were measured. Samples were excited using an intracavity
doubled argon-ion laser, and the spectra were recorded with
a single grating spectrograph and a liquid nitrogen-cooled
charge-coupled device.},
Key = {99020017723}
}
@article{6060639,
Author = {Chance, B. and Cope, M. and Gratton, E. and Ramanujam, N. and Tromberg, B.},
Title = {Phase measurement of light absorption and scatter in human
tissue},
Journal = {Rev. Sci. Instrum. (USA)},
Volume = {69},
Number = {10},
Pages = {3457 - 81},
Year = {1998},
url = {http://dx.doi.org/10.1063/1.1149123},
Keywords = {biomedical equipment;biomedical imaging;biomedical
measurement;brain;demodulation;frequency-domain
analysis;laser applications in medicine;light
absorption;light scattering;muscle;optical tomography;phase
locked loops;phase measurement;phase modulation;photodetectors;photon
transport theory;reviews;},
Abstract = {Analog and digital technologies are presented for precise
measurement of propagation delay of photons from source and
detector placed on portions of the human body. The goal of
the apparatus design is to quantify absorption
(μ<sub>a</sub>) and scattering (μ<sub>s</sub><sup>'</sup>)
induced by biological pigments and biological structures,
respectively. Body tissues are highly scattering with a mean
distance between scatterers of less than a mm (at 700-850
nm). Significant absorption is mainly due to 5%-10% of the
tissue volume occupied by blood. Measurement of
μ<sub>a</sub> and μ<sub>s</sub><sup>'</sup> is done by
both time and frequency domain equipment. This article
focuses upon frequency domain equipment because of its
simplicity, reduced noise bandwidth, versatility, and the
strong analogy to very high frequency/ultrahigh frequency
communication devices, particularly those using phase
modulation. Comparisons are made of homodyne and heterodyne
systems together with evaluation of single and multiple side
band systems, with particular emphasis on methods for
multiplexed optical and radio frequencies by frequency
encoding or time-sharing technologies. The applications of
these phase modulation systems to quantitative brain and
muscle blood oximetry, functional activity of the forebrain,
and other important problems of medical science, are
presented},
Key = {6060639}
}
@article{98104412480,
Author = {Mahadevan-Jansen, Anita and Mitchell, Michele Follen and Ramanujam, Nirmala and Malpica, Anais and Thomsen, Sharon and Richards-Kortum, Rebecca},
Title = {Near-infrared Raman spectroscopy for in vitro detection of
cervical precancers},
Journal = {Photochemistry and Photobiology},
Volume = {68},
Number = {1},
Pages = {123 -},
Year = {1998},
url = {http://dx.doi.org/10.1562/0031-8655(1998)068<0123:NIRSFV>2.3.CO;2},
Key = {98104412480}
}
@article{98114473902,
Author = {Mahadevan-Jansen, Anita and Mitchell, Michele Follen and Ramanujam, Nirmala and Utzinger, Urs and Richards-Kortum,
Rebecca},
Title = {Development of a fiber optic probe to measure NIR Raman
spectra of cervical tissue in vivo},
Journal = {Photochemistry and Photobiology},
Volume = {68},
Number = {3},
Pages = {427 -},
Year = {1998},
url = {http://dx.doi.org/10.1562/0031-8655(1998)068<0427:DOAFOP>2.3.CO;2},
Key = {98114473902}
}
@article{5997499,
Author = {Ramanujam, N. and Du, C. and Ma, H.Y. and Chance,
B.},
Title = {Sources of phase noise in homodyne and heterodyne phase
modulation devices used for tissue oximetry
studies},
Journal = {Rev. Sci. Instrum. (USA)},
Volume = {69},
Number = {8},
Pages = {3042 - 54},
Year = {1998},
url = {http://dx.doi.org/10.1063/1.1149053},
Keywords = {adjacent channel interference;biomedical
electronics;biomedical equipment;biomedical
measurement;demodulation;electro-optical modulation;laser
applications in medicine;optical crosstalk;phase
modulation;phase noise;photodetectors;shot
noise;},
Abstract = {The objective of this study was to characterize sources of
phase noise in homodyne and heterodyne phase modulation
devices (PMDs) used for tissue oximetry measurements. Each
PMD incorporates a laser diode modulated at a radio
frequency in the 50-200 MHz range, an optical detector and a
homodyne/heterodyne phase sensitive detector. The intensity
modulated light which propagates through tissue is
attenuated and undergoes a phase shift, which reflects the
mean time of flight of the photons through the tissue. The
measured amplitude and phase can be used to determine
hemoglobin saturation in tissues using equations based on
diffusion theory. Four studies were performed to
characterize the sources of phase noise. First, the signal
to noise ratio was characterized to determine if the PMDs
are operating at the shot noise or detector noise limit.
Second, the accuracy of the three PMDs for measuring phase
shifts in tissue were compared by using them to measure the
phase shift as a function of path length change in air, at a
constant amplitude, and at signal to noise ratios comparable
to that measured from tissue. The third source of noise
measured was the phase shift that results from optical
attenuation of the signal (phase-amplitude cross talk) at a
constant path length, to characterize intensity dependent
phase shifts in the PMDs. Finally, the interchannel
interference of a dual wavelength PMD which uses radio
frequency multiplexing to perform phase measurements at two
wavelengths simultaneously was compared to that of a dual
wavelength PMD which uses time multiplexing to perform phase
measurements at two wavelengths serially to determine the
effect of each on phase error},
Key = {5997499}
}
@article{5994807,
Author = {Tumer, K. and Ramanujam, N. and Ghosh, J. and Richards-Kortum, R.},
Title = {Ensembles of radial basis function networks for
spectroscopic detection of cervical precancer},
Journal = {IEEE Trans. Biomed. Eng. (USA)},
Volume = {45},
Number = {8},
Pages = {953 - 61},
Year = {1998},
url = {http://dx.doi.org/10.1109/10.704864},
Keywords = {feedforward neural nets;fluorescence spectroscopy;laser
applications in medicine;medical signal processing;multilayer
perceptrons;spectral analysis;spectroscopy
computing;statistical analysis;},
Abstract = {The mortality related to cervical cancer can be
substantially reduced through early detection and treatment.
However, current detection techniques, such as Pap smear and
colposcopy, fail to achieve a concurrently high sensitivity
and specificity. In vivo fluorescence spectroscopy is a
technique which quickly, noninvasively and quantitatively
probes the biochemical and morphological changes that occur
in precancerous tissue. A multivariate statistical algorithm
was used to extract clinically useful information from
tissue spectra acquired from 361 cervical sites from 95
patients at 337-, 380-, and 460-nm excitation wavelengths.
The multivariate statistical analysis was also employed to
reduce the number of fluorescence excitation-emission
wavelength pairs required to discriminate healthy tissue
samples from precancerous tissue samples. The use of
connectionist methods such as multilayered perceptrons,
radial basis function (RBF) networks, and ensembles of such
networks was investigated. RBF ensemble algorithms based on
fluorescence spectra potentially provide automated and near
real-time implementation of precancer detection in the hands
of nonexperts. The results are more reliable, direct, and
accurate than those achieved by either human experts or
multivariate statistical algorithms},
Key = {5994807}
}
@article{6097345,
Author = {Trujillo, E.V. and Sandison, D.R. and Utzinger, U. and Ramanujam, N. and Mitchell, M.F. and Richards-Kortum,
R.},
Title = {Method to determine tissue fluorescence efficiency in vivo
and predict signal-to-noise ratio for spectrometers},
Journal = {Appl. Spectrosc. (USA)},
Volume = {52},
Number = {7},
Pages = {943 - 51},
Year = {1998},
url = {http://dx.doi.org/10.1366/0003702981944751},
Keywords = {biological effects of optical radiation;biological
tissues;cancer;fluorescence;patient diagnosis;},
Abstract = {Recent clinical trials have demonstrated the potential of
fluorescence spectroscopy for in vivo diagnosis of
pathology. There is significant potential to reduce the cost
and complexity of instrumentation to measure tissue spectra;
however, careful analysis is required to maximize
performance and minimize cost. One measure of performance is
the signal-to-noise ratio (SNR) off the resulting data. This
paper describes a method to predict the SNR of a given
optical design for a particular tissue application. In order
to calculate the expected SNR, two pieces of information are
required: (1) the throughput and inherent noise of the
system and (2) a quantitative relationship between the
illumination energy and the resulting tissue fluorescence
available for collection, which we define as the tissue
fluorescence efficiency (FE). We present a method to
calculate the fluorescence efficiency of tissue from in vivo
measurements of tissue fluorescence. We report FE
measurements of the normal and precancerous human cervix in
vivo at 337, 380, and 460 nm excitation. We also present and
evaluate a method to estimate the throughput and noise of
various spectrometers and predict the expected SNR for
tissue spectra by using the measured tissue FE. For squamous
cervical tissue, as the degree of the disease increases, FE
decreases, and as the excitation wavelength increases, FE
decreases, Cervical tissue FE varies more than two orders of
magnitude, depending on the tissue type and on the
excitation wavelength used. Our SNR calculations, based on
measured values of tissue FE, demonstrate agreement within a
factor of 1.3 of the measured SNR on average. This method
can be used to estimate the performance of different
spectrometer designs for clinical use},
Key = {6097345}
}
@article{96113424305,
Author = {Ramanujam, Nirmala and Mitchell, Michele Follen and Mahadevan-Jansen, Anita and Thomsen, Sharon L. and Staerkel,
Gregg and Malpica, Anais and Wright, Thomas and Atkinson,
Neely and Richards-Kortum, Rebecca},
Title = {Cervical precancer detection using a multivariate
statistical algorithm based on laser-induced fluorescence
spectra at multiple excitation wavelengths},
Journal = {Photochemistry and Photobiology},
Volume = {64},
Number = {4},
Pages = {720 -},
Year = {1996},
Key = {96113424305}
}
@article{5349815,
Author = {Richards-Kortum, R. and Mahadevan-Jansen, A. and Ramanujam,
N.},
Title = {Optical spectroscopy vs. the surgical suite [cancer
detection]},
Journal = {IEEE Circuits Devices Mag. (USA)},
Volume = {12},
Number = {4},
Pages = {34 - 40},
Year = {1996},
url = {http://dx.doi.org/10.1109/101.526878},
Keywords = {fluorescence spectroscopy;patient diagnosis;Raman
spectroscopy;},
Abstract = {A novel non-invasive technique for detecting cancer and
precancer offers a viable adjunct to biopsies. Here, we
summarize the principles of optical spectroscopy and present
some of the highlights obtained with the successful
application of fluorescence and Raman spectroscopy for
cancer and precancer detection},
Key = {5349815}
}
@article{95062742467,
Author = {Mahadevan, Anita and Ramanujam, Nirmala and Mitchell,
Michele F. M.D. and Malpica, Anais M.D. and Thomsen, Sharon
L. M.D. and Richards-Kortum, Rebecca R.},
Title = {Optical techniques for diagnosis of cervical precancers: a
comparison of Raman and fluorescence spectroscopies},
Journal = {Proceedings of SPIE - The International Society for Optical
Engineering},
Volume = {2388},
Pages = {110 - 120},
Address = {San Jose, CA, USA},
Year = {1995},
url = {http://dx.doi.org/10.1117/12.208469},
Keywords = {Raman spectroscopy;Diagnosis;Infrared radiation;Fluorescence;Algorithms;Raman
scattering;Tissue;Optimization;},
Abstract = {In vivo fluorescence measurements were followed by in vitro
NIR Raman measurements on 36 human cervical biopsies, 18
with suspected cervical dysplasia. Fluorescence spectra
collected at 337 and 460 nm excitation were used to develop
a diagnostic algorithm to differentiate between normal and
dysplastic tissues. Using a fluorescence algorithm optimized
on another much larger data set, a sensitivity and
specificity of 80% and 67% were observed for differentiating
squamous intraepithelial lesions (SILs) from all other
tissues for the 36 samples. In general, inflammation and
metaplasia samples were misclassified at SILs in the larger
sample set. A sensitivity and specificity of 57% and 100%
were achieved for differentiating high grade from low grade
SILs using a second fluorescence algorithm developed with a
larger sample set. Using Raman scattering peaks observed at
626 and 1070 cm<sup>-1</sup>, SILs could be separated from
other tissues with a sensitivity and specificity of 88% and
100% in an algorithm optimized on the data set consisting of
the 36 samples from this study. In addition, inflammation
and metaplasia samples are correctly separated from the
SILs. The band at 1656 cm<sup>-1</sup> could differentiate
both SILs from all other tissues as well as high grade from
low grade lesions with a sensitivity of 91% and 88% and
specificity of 86% and 100%, again using an algorithm
optimized on the set of 36 samples. However, these
encouraging results must be considered preliminary because
of the small sample size. Performance of the fluorescence
algorithm to differentiate SILs from squamous normals
(sensitivity = 84%, specificity = 82%) was higher than was
observed with a smaller data set when tested retrospectively
on a larger prediction set of 237 samples.},
Key = {95062742467}
}
@article{5040407,
Author = {Jayakumar, J. and Ramanujam, N.},
Title = {A computational method for solving quasilinear singular
perturbation problems},
Journal = {Appl. Math. Comput. (USA)},
Volume = {71},
Number = {1},
Pages = {1 - 14},
Year = {1995},
url = {http://dx.doi.org/10.1016/0096-3003(94)00077-H},
Keywords = {boundary-value problems;differential equations;finite
difference methods;},
Abstract = {A class of quasilinear, singularly-perturbed, two-point,
boundary value problems for second-order, ordinary
differential equations without interior turning points is
considered. To solve these problems Newton's method of
quasilinearization is adopted. Then the resultant linear
problems are solved by a numerical method. This method is a
combination of an exponentially-fitted finite difference
method and a classical numerical method. Further, it is
based on the boundary value technique generally used to
solve singularly-perturbed boundary value problems. Error
estimates for the numerical solution of linear problems are
stated. Some examples are given to illustrate the
method},
Key = {5040407}
}
@article{4608911,
Author = {Jayakumar, J. and Ramanujam, N.},
Title = {A numerical method for singular perturbation problems
arising in chemical reactor theory},
Journal = {Comput. Math. Appl. (UK)},
Volume = {27},
Number = {5},
Pages = {83 - 99},
Year = {1994},
url = {http://dx.doi.org/10.1016/0898-1221(94)90078-7},
Keywords = {boundary-value problems;chemical reactions;chemical
technology;differential equations;perturbation
theory;},
Abstract = {A class of singularly perturbed two point boundary value
problems for second order ordinary differential equations
with mixed boundary conditions, arising in chemical reactor
theory is considered. In order to solve them, a numerical
method is suggested, in which an exponentially fitted
difference scheme is combined with classical numerical
methods. The proposed method is distinguished by the
following facts: first, the authors divide the given
interval (the domain of definition of the differential
equation) into two subintervals called outer and inner
regions. Then, they solve the differential equation over
both the regions as two point boundary value problems. The
terminal boundary condition of the inner region is obtained
using the zero order asymptotic expansion of the solution.
Some numerical examples are given to illustrate the
method},
Key = {4608911}
}
@article{4636928,
Author = {Durkin, A.J. and Jaikumar, S. and Ramanujam, N. and Richards-Kortum, R.},
Title = {Relation between fluorescence spectra of dilute and turbid
samples},
Journal = {Appl. Opt. (USA)},
Volume = {33},
Number = {3},
Pages = {414 - 23},
Year = {1994},
Keywords = {biological techniques and instruments;fluorescence;light
scattering;visible spectra of organic molecules and
substances;},
Abstract = {We present a method to extend rank-annihilation-factor
analysis (RAFA) for the analysis of fluorescence from
homogeneous turbid samples. The method is based on a
fundamental relationship between the fluorescence of a
dilute solution and that of a turbid solution. We have
derived this relationship, known as the transfer function,
for turbid materials using the two-flux Kubelka-Munktheory
theory. The method is tested with spectroscopic data from
optically thin and turbid samples of the media of a human
aorta. At 450-nm excitation, agreement between the measured
and predicted dilute-solution fluorescence spectra is within
5% at all emission wavelengths; at 340-nm excitation,
agreement is within 20% at all wavelengths, with some
residual Soret-band absorption. The simulations presented
indicate that the transfer function is markedly more
sensitive to absorption than to scattering
properties},
Key = {4636928}
}
@article{8409588,
Author = {Lubawy, C. and Ramanujam, N.},
Title = {Endoscopically compatible near-infrared photon migration
probe},
Journal = {Opt. Lett. (USA)},
Volume = {29},
Number = {17},
Pages = {2022 - 4},
Year = {1},
Keywords = {absorption coefficients;bio-optics;biological
organs;biological tissues;biomedical optical
imaging;endoscopes;fibre optic sensors;gynaecology;infrared
imaging;phantoms;sampling methods;},
Abstract = {We have developed a 2.3-mm-diameter fiber-optic probe for
near-infrared photon migration spectroscopy that can be
inserted into the body through an endoscope or biopsy
needle. This probe is specifically designed to be inserted
into a core biopsy needle to facilitate optical sampling of
lesions during breast needle biopsy. This probe was tested
on tissue phantoms containing heterogeneities (to stimulate
breast lesions) of various sizes and optical properties.
Under the conditions tested, the probe can measure the
absorption coefficient to within 30% for heterogeneities
with radii as small as 10 mm},
Key = {8409588}
}
@article{8379203,
Author = {Quan Liu and Ramanujam, N.},
Title = {Experimental proof of the feasibility of using an angled
fiber-optic probe for depth-sensitive fluorescence
spectroscopy of turbid media},
Journal = {Opt. Lett. (USA)},
Volume = {29},
Number = {17},
Pages = {2034 - 6},
Year = {1},
url = {http://dx.doi.org/10.1364/OL.29.002034},
Keywords = {bio-optics;biomedical measurement;biomedical optical
imaging;cancer;fibre optic sensors;fluorescence;Monte Carlo
methods;phantoms;physiological models;skin;turbidity;},
Abstract = {An angled fiber-optic probe that facilitates depth-sensitive
fluorescence measurements was developed for enhancing
detection of epithelial precancers. The probe was tested on
solid, two-layered phantoms and proved to be effective in
selectively detecting fluorescence from different layers.
Specifically, a larger illumination angle provides greater
sensitivity to fluorescence from the top layer as well as
yielding an overall higher fluorescence signal. Monte Carlo
simulations of a theoretical model of the phantoms
demonstrate that increasing the illumination angle results
in an increased excitation photon density and, thus, in
increased fluorescence generated in the top
layer},
Key = {8379203}
}
@article{7032107,
Author = {Ramanujam, N. and Jinxian Chen and Gossage, K. and Richards-Kortum, R. and Chance, B.},
Title = {Fast and noninvasive fluorescence imaging of biological
tissues in vivo using a flying-spot scanner},
Journal = {IEEE Trans. Biomed. Eng. (USA)},
Volume = {48},
Number = {9},
Pages = {1034 - 41},
url = {http://dx.doi.org/10.1109/10.942594},
Keywords = {biological tissues;biomedical imaging;cancer;fluorescence;laser
applications in medicine;photomultipliers;},
Abstract = {The authors have developed a flying-spot scanner (FSS), for
fluorescence imaging of tissues in vivo. The FSS is based on
the principles of single-pixel illumination and detection
via a raster scanning technique. The principal components of
the scanner are a laser light source, a pair of horizontal
and vertical scanning mirrors to deflect the laser light in
these respective directions on the tissue surface, and a
photo multiplier tube (PMT) detector. This paper
characterizes the performance of the FSS for fluorescence
imaging of tissues in vivo. First, a signal-to-noise ratio
(SNR) analysis is presented. This is followed by
characterization of the experimental SNR, linearity and
spatial resolution of the FSS. Finally, the feasibility of
tissue fluorescence imaging is demonstrated using an animal
model. In summary, the performance of the FSS is comparable
to that of fluorescence-imaging systems based on multipixel
illumination and detection. The primary advantage of the FSS
is the order-of-magnitude reduction in the cost of the light
source and detector. However, the primary disadvantage of
the FSS its significantly slower frame rate (1 Hz). In
applications where high frame rates are not critical, the
FSS will represent a low-cost alternative to multichannel
fluorescence imaging-systems},
Key = {7032107}
}
%% Other
@misc{fds195294,
Author = {Kennedy S and Mueller J and Bydlon T and Brown JQ and Ramanujam
N},
Title = {Using wide-field quantitative diffuse reflectance
spectroscopy in combination with high-resolution imaging for
margin assessment},
Journal = {Proc. of SPIE, Vol. 7890, San Francisco,
CA.},
Year = {2011},
Key = {fds195294}
}
@misc{fds195295,
Author = {Chang VTC and Merisier D and Yu B and Walmer D and Ramanujam
N},
Title = {Calibration Schemes of a Field-compatible Optical
Spectroscopic System to Quantify Neovascular Changes in the
Dysplastic Cervix},
Journal = {Proc. of SPIE, Vol. 7890, San Francisco,
CA.},
Year = {2011},
Key = {fds195295}
}
@misc{fds195296,
Author = {Brown JQ and Bydlon TM and Kennedy SA and Geradts J and Wilke LG and Richards LM and Junker M and Gallagher J and Ramanujam
N},
Title = {Assessment of breast tumor margins via quantitative spectral
reflectance imaging},
Journal = {Invited paper, Biomedical Applications of Light Scattering
IV, SPIE Photonics West - BIOS Conference Proceedings v.
7573, San Francisco, CA.},
Year = {2010},
Key = {fds195296}
}
@misc{fds195297,
Author = {Brown JQ and Yu B and Ramanujam N},
Title = {Tissue-mimicking phantoms for system calibration and
validation in Quantitative Diffuse Reflectance Spectroscopy
(Q-DRS)},
Journal = {Design and Performance Validation of Phantoms used in
Conjunction with Optical Measurement of Tissue III, SPIE
Photonics West - BIOS, San Francisco, CA.},
Year = {2010},
Key = {fds195297}
}
@article{9187405,
Author = {Lazebnik, M. and Changfang Zhu and Palmer, G. and Harter, J. and Sewall, S. and Ramanujam, N. and Hagness,
S.C.},
Title = {Comparison of electromagnetic properties of normal breast
tissue at optical and microwave frequencies},
Journal = {2006 IEEE Antennas and Propagation Society International
Symposium (IEEE Cat. No. 06CH37758C)},
Pages = {397 -},
Address = {Albuquerque, NM, USA},
Year = {2006},
Keywords = {cancer;infrared spectroscopy;medical signal
processing;microwave measurement;microwave
spectroscopy;},
Abstract = {The goal of this study is to simultaneously perform
microwave and optical spectroscopy measurements on normal
tissue samples obtained from breast reduction surgeries and
correlate the findings},
Key = {9187405}
}
@article{7996335,
Author = {Choe, R. and Durduran, T. and Guoqiang Yu and Nijland,
M.J.M. and Nathanielsz, P.W. and Chance, B. and Yodh, A.G. and Ramanujam, N.},
Title = {Noninvasive cerebral hemoglobin oxygenation quantification
of fetal sheep under hypoxic stress in-utero using
frequency-domain diffuse optical two-layer
model},
Journal = {Proc. SPIE - Int. Soc. Opt. Eng. (USA)},
Volume = {4955},
Number = {1},
Pages = {379 - 87},
Address = {San Jose, CA, USA},
Year = {2003},
url = {http://dx.doi.org/10.1117/12.478175},
Keywords = {bio-optics;biological techniques;blood vessels;frequency-domain
analysis;haemodynamics;infrared spectroscopy;oxygen;proteins;veterinary
medicine;},
Abstract = {A study using pregnant sheep was designed to simulate fetal
hypoxia in order to investigate the ability of near-infrared
spectroscopy (NIRS) to detect and quantify fetal hypoxia in
utero. The near-infrared spectroscopic probe consisted of
two detectors and six source positions. It was placed on the
maternal ewe abdomen above the fetal head. The light sources
were modulated at 70 MHz and frequency-encoded so that
simultaneous measurements at 675, 786, 830 nm for each
source position were possible. After the baseline
measurements, fetal hypoxia was induced by blocking the
aorta of pregnant ewe and thus compromising the blood supply
to the uterus. Blood gas samples were concurrently drawn
from the fetal brachial artery and jugular veins. Analysis
of the diffuse optical data used a two-layer model to
separate the maternal layer from the fetal head. The
analysis also employed a priori spectral information about
tissue chromophores. This approach provided good
quantification of blood oxygenation changes, which
correlated well with the blood gas analyses. By contrast the
homogeneous model underestimated oxygenation changes during
hypoxia},
Key = {7996335}
}
@article{7748523,
Author = {Ramanujam, N. and Palmer, G. and Breslin, T. and Gichrist,
K.},
Title = {Diagnosis of breast cancer using auto fluorescence and
diffuse reflectance spectroscopy},
Journal = {Conference Proceedings. Second Joint EMBS-BMES Conference
2002. 24th Annual International Conference of the
Engineering in Medicine and Biology Society. Annual Fall
Meeting of the Biomedical Engineering Society (Cat.
No.02CH37392)},
Volume = {vol.3},
Pages = {2279 - 80},
Address = {Houston, TX, USA},
Year = {2002},
url = {http://dx.doi.org/10.1109/IEMBS.2002.1053281},
Keywords = {bio-optics;biological organs;cancer;fluorescence
spectroscopy;gynaecology;patient diagnosis;reflectivity;},
Abstract = {Proof-of-principle studies were carried out to assess the
diagnostic potential of auto fluorescence and diffuse
reflectance spectroscopy for discriminating between
malignant and non-malignant breast tissues, ex vivo. Auto
fluorescence spectra at excitation wavelengths of 300,320
and 340 nm were found to be most effective in
differentiating malignant (13) from non-malignant tissues
(25) in this pilot investigation},
Key = {7748523}
}
@article{7769352,
Author = {Tompkins, W.J. and Beebe, D. and Gimm, J.A. and Nicosia, M. and Ramanujam, N. and Thompson, P. and Tyler, M.E. and Webster, J.G.},
Title = {A design backbone for the biomedical engineering
curriculum},
Journal = {Conference Proceedings. Second Joint EMBS-BMES Conference
2002. 24th Annual International Conference of the
Engineering in Medicine and Biology Society. Annual Fall
Meeting of the Biomedical Engineering Society (Cat.
No.02CH37392)},
Volume = {vol.3},
Pages = {2595 - 6},
Address = {Houston, TX, USA},
Year = {2002},
url = {http://dx.doi.org/10.1109/IEMBS.2002.1053443},
Keywords = {biomedical education;design engineering;reviews;},
Abstract = {In this paper, we summarize our experiences as advisors
supervising biomedical engineering design projects in the
design backbone of our curriculum, the six-semester design
course sequence required for all biomedical engineering
majors at the University of Wisconsin-Madison},
Key = {7769352}
}
@article{7313461,
Author = {Vishnoi, G. and Choe, R. and Ramanujam, N. and Rode, M.E. and Nioka, S. and Chance, B.},
Title = {Quantification of fetal blood parameters using non-invasive
optical techniques},
Journal = {Technical Digest. CLEO/Pacific Rim 2001. 4th Pacific Rim
Conference on Lasers and Electro-Optics (Cat.
No.01TH8557)},
Volume = {vol.1},
Pages = {380 - 1},
Address = {Chiba, Japan},
Year = {2001},
url = {http://dx.doi.org/10.1109/CLEOPR.2001.967884},
Keywords = {biomedical imaging;blood;infrared imaging;infrared
spectroscopy;obstetrics;oximetry;},
Abstract = {This paper describes the techniques and methodologies
utilized for the quantification of fetal and neonatal blood
parameters using trans-abdominal, noninvasive optical
techniques. It also reports the results obtained on the
localization of fetal head using frequency domain
spectrometer studies on vibro-acoustic stimulation},
Key = {7313461}
}
@article{7022990,
Author = {Ramanujam, N. and Puc, A.B. and Lenner, G. and Kidorf, H.D. and Davidson, C.R. and Hayee, I. and Cai, J.-X. and Nissov,
M. and Pilipetskii, A. and Rivers, C. and Bergano,
N.S.},
Title = {Forward error correction (FEC) techniques in long-haul
optical transmission systems},
Journal = {LEOS 2000. 2000 IEEE Annual Meeting Conference Proceedings.
13th Annual Meeting. IEEE Lasers and Electro-Optics Society
2000 Annual Meeting (Cat. No.00CH37080)},
Volume = {vol.2},
Pages = {405 - 6},
Address = {Rio Grande, Puerto Rico},
Year = {2000},
url = {http://dx.doi.org/10.1109/LEOS.2000.893884},
Keywords = {error correction codes;forward error correction;optical
crosstalk;optical fibre communication;optical fibre
dispersion;optical fibre losses;wavelength division
multiplexing;},
Abstract = {The use of FEC provides significant coding gain, which has
been used to demonstrate error-free transmission (1) under
severely errored operating conditions, (2) with high
spectral efficiency, (3) over distances exceeding 10,000 km,
and (4) at high bit rates. Recent experiments using FEC have
demonstrated aggregate transmission capacity approaching 2
Tb/s. Most importantly, FEC-coded transmission can tolerate
a lower optical SNR on the line, which in turn reduces
impairments induced by nonlinearity, with the net effect
being an increase in the Q<sup>2</sup>-factor when signal
power is reduced. There is presently significant activity
directed towards developing more powerful codes as well as
more efficient decoding algorithms},
Key = {7022990}
}
@article{99124936175,
Author = {Choe, Regine and Vishnoi, Gargi and Ramanujam, Nirmala and Ntziachristos, Vasilis and Nioka, Shoko and Chance, Britton and Yodh, Arjun G. and Rode, Martha and Forouzan, Iraj and Morgan, Mark},
Title = {Feasibility of frequency domain NIR spectrometer to measure
fetal cerebral blood oxygenation in-utero},
Journal = {Proceedings of SPIE - The International Society for Optical
Engineering},
Volume = {3597},
Pages = {661 - 668},
Address = {San Jose, CA, USA},
Year = {1999},
url = {http://dx.doi.org/10.1117/12.356782},
Keywords = {Infrared spectrometers;Hemoglobin oxygen
saturation;Blood;Tissue;Algorithms;Optical
properties;Infrared spectroscopy;Light propagation;},
Abstract = {The feasibility of using a frequency domain spectrometer for
measuring fetal cerebral blood oxygenation in-utero at 750
and 780 nm of modulation at 70 MHz was investigated.
Clinical data was recorded during the elective Cesarean
section of human subjects. The measurements were made on
maternal abdomen in the post-epidural stage and on the
fontanel region of neonate before and after the umbilical
cord was detached. The deoxygenated and oxygenated
hemoglobin concentration, blood volume and saturation were
calculated based on μ<sub>α</sub> of 2 wavelength.
The post-epidural blood saturation value correlated well
with the pre-cord saturation value.},
Key = {99124936175}
}
@article{99124936176,
Author = {Zourabian, A. and Siegel, A. and Ramanujam, N. and Chance,
B. and Boas, D.A. and Vishnoi, B.G. and Choe,
R.},
Title = {Non-invasive trans-abdominal monitoring of fetal cerebral
oxygenation using pulse oximetry},
Journal = {Proceedings of SPIE - The International Society for Optical
Engineering},
Volume = {3597},
Pages = {669 - 675},
Address = {San Jose, CA, USA},
Year = {1999},
url = {http://dx.doi.org/10.1117/12.356783},
Keywords = {Hemoglobin oxygen saturation;Noninvasive medical
procedures;Patient monitoring;Tissue;Mathematical
models;Blood;Volume fraction;Optical instruments;Cardiology;},
Abstract = {Pulse oximetry (oxygen saturation monitoring) has markedly
improved medical care in many fields, including
anesthesiology, intensive care, and newborn intensive care.
In obstetrics, fetal heart rate monitoring remains the
standard for intrapartum assessment of fetal well being.
Fetal oxygen saturation monitoring is a new technique
currently under development. It is potentially superior to
electronic fetal heart rate monitoring (cardiotocography)
because it allows direct assessment of both fetal oxygen
status and fetal tissue perfusion. Here, we present
feasibility studies for trans-abdominal fetal cerebral pulse
oximetry. Our experiments on more than 20 patients indicate
feasibility. We will present the methodology for obtaining
these data, as well as a summary of our pilot clinical
study.},
Key = {99124936176}
}
@article{99124936174,
Author = {Vishnoi, Gargi and Hielscher, Andreas H. and Ramanujam,
Nirmala and Nioka, Shoko and Chance, Britton},
Title = {Tissue phantom studies on photon migration through fetal
brain in-utero using near infra-red spectroscopy},
Journal = {Proceedings of SPIE - The International Society for Optical
Engineering},
Volume = {3597},
Pages = {650 - 660},
Address = {San Jose, CA, USA},
Year = {1999},
url = {http://dx.doi.org/10.1117/12.356788},
Keywords = {Spectrometers;Brain;Infrared spectroscopy;Photons;Computer
simulation;Geometry;Imaging techniques;Numerical
methods;},
Abstract = {We present tissue phantom experimental results and
theoretical simulations to study photon migration through
the fetal head in-utero. A continuous-wave (CW), dual
wavelength (760 & 850 nm) spectrometer was developed and
employed for the experiments at a source-detector separation
of 10 cm. Theoretical simulations were performed using
time-independent, finite-difference, discrete-ordinate,
radiative-transport and diffusion equations. Two phantom
geometries viz. circular and rectangular were considered.
The tissue phantom incorporates a fetal head (absorption
coefficient, μa: 0.15 cm<sup>-1</sup> & reduced
scattering coefficient, µs': 5.0 cm<sup>-1</sup>), an
amniotic fluid sac (μa=0.02 cm<sup>-1</sup>, µs'=
0.1 cm<sup>-1</sup>) and a maternal tissue layer (μa=
0.08 cm<sup>-1</sup>, µs'= 5.0 cm<sup>-1</sup>).
Photon fluence from the tissue phantom was quantified as a
function of fetal head depth and its position relative to
probe placement. Experimental results obtained with
spectrometer were found to be congruent with theoretical
results and clinical investigations. The results indicate
that photon fluence decreases with increase in fetal head
depth for circular geometry, while it increases with
increase in fetal head depth for rectangular geometry. This
paradoxical result observed may be attributed to the effect
of amniotic fluid in the light path. Photon fluence is
sensitive for fetal head depths within 40 mm. This is well
within the fetal head depths expected in near-term patients
(approx. 20 mm).},
Key = {99124936174}
}
@article{5869690,
Author = {Trujillo, E.V. and Sandison, D. and Ramanujam, N. and Follen-Mitchell, M. and Cantor, S. and Richards-Kortum,
R.},
Title = {Development of a cost-effective optical system for detection
of cervical pre-cancer},
Journal = {Proceedings of the 18th Annual International Conference of
the IEEE Engineering in Medicine and Biology Society.
`Bridging Disciplines for Biomedicine' (Cat.
No.96CH36036)},
Volume = {vol.1},
Pages = {191 - 3},
Address = {Amsterdam, Netherlands},
Year = {1997},
url = {http://dx.doi.org/10.1109/IEMBS.1996.656911},
Keywords = {cost-benefit analysis;fluorescence spectroscopy;laser
applications in medicine;patient diagnosis;},
Abstract = {Cervical cancer is an important problem. The incidence of
cervical pre-cancer is increasing, and unless current
diagnostic techniques are improved, mortality and cost may
increase substantially. The goal of our project is to find
the most cost-effective optical system for the detection of
cervical pre-cancer. Our hypothesis is that using
fluorescence spectroscopy, a new technique for detection of
cervical cancer and pre-cancer, will maintain the current
technique's sensitivity, increase its specificity, and
reduce its cost. In this paper we present a new method to
calculate the fluorescence efficiency (FE) of human cervical
tissue, based on in vivo measurements of 381 sites from 95
patients. This value is used in signal to noise ratio (SNR)
calculations to evaluate the performance of different
optical systems for detection of cervical pre-cancer. We
verify that the predicted SNR values, obtained using FE,
agree with the SNR of the patient's spectral data. We use
the resulting data to generate a receiver-operator
characteristic (ROC) curve that compares spectroscopy to the
current standard of care. Finally, preliminary results of
our economic analysis estimate that use of fluorescence
spectroscopy could save $2.1 billion annually in the
US},
Key = {5869690}
}
@article{5767981,
Author = {Tumer, K. and Ramanujam, N. and Richards-Kortum, R. and Ghosh, J.},
Title = {Spectroscopic detection of cervical pre-cancer through
radial basis function networks},
Journal = {Advances in Neural Information Processing Systems 9.
Proceedings of the 1996 Conference},
Pages = {981 - 7},
Address = {Denver, CO, USA},
Year = {1997},
Keywords = {feedforward neural nets;fluorescence spectroscopy;medical
expert systems;patient diagnosis;real-time
systems;},
Abstract = {The mortality related to cervical cancer can be
substantially reduced through early detection and treatment.
However, current detection techniques, such as Pap smear and
colposcopy, fail to achieve a concurrently high sensitivity
and specificity. In vivo fluorescence spectroscopy is a
technique which quickly, noninvasively and quantitatively
probes the biochemical and morphological changes that occur
in pre-cancerous tissue. RBF ensemble algorithms based on
such spectra provide automated, and near real-time
implementation of pre-cancer detection in the hands of
nonexperts. The results are more reliable, direct and
accurate than those achieved by either human experts or
multivariate statistical algorithms},
Key = {5767981}
}
@article{97013505596,
Author = {Ramanujam, Nirmala and Follen-Mitchell, Michele and Mahadevan-Jansen, Anita and Pitris, Costas and Agrawal,
Anant and Thomsen, Sharon L. M.D. and Staerkel, Gregg and Wright, Thomas and Richards-Kortum, Rebecca
R.},
Title = {Detection of cervical precancer using optical spectroscopy
(Extended Abstract)},
Journal = {Proceedings of SPIE - The International Society for Optical
Engineering},
Volume = {2926},
Pages = {21 - 22},
Address = {Vienna, Austria},
Year = {1996},
url = {http://dx.doi.org/10.1117/12.260814},
Keywords = {Infrared spectroscopy;Medical applications;Oncology;Infrared
spectroscopy;Diagnosis;Fluorescence;Raman
spectroscopy;},
Abstract = {The continuing morbidity and mortality rate related to
cervical cancer necessitates an improvement in current
screening and diagnostic programs that target early
detection of its curable precursor, cervical squamous
intraepithelial lesion (SIL). Optical spectroscopy is a
technique that has the capability to improve the accuracy
and efficacy of current techniques for the detection of
SILs. We have utilized fluorescence spectroscopy for the
differential detection of SILs, in vivo and we have also
evaluated the utility of near infrared (IR) Raman
spectroscopy for the characterization of SILs in
vitro.},
Key = {97013505596}
}
@article{98034112829,
Author = {Trujillo, E.V. and Sandison, D. and Ramanujam, N. and Follen-Mitchell, M. and Cantor, S. and Richards-Kortum,
R.},
Title = {Development of a cost-effective optical system for detection
of cervical pre-cancer},
Journal = {Annual International Conference of the IEEE Engineering in
Medicine and Biology - Proceedings},
Number = {1},
Pages = {191 - 193},
Address = {Amsterdam, Neth},
Year = {1996},
Keywords = {Optical systems;Oncology;Cost effectiveness;Fluorescence;Tissue;Signal
to noise ratio;Spectroscopy;},
Abstract = {Cervical cancer is an important problem. The incidence of
cervical pre-cancer is increasing, and unless current
diagnostic techniques are improved, mortality and cost may
increase substantially. The goal of our project is to find
the most cost-effective optical system for the detection of
cervical pre-cancer. Our hypothesis is that using
fluorescence spectroscopy, a new technique for detection of
cervical cancer and pre-cancer, will maintain the current
technique's sensitivity, increase its specificity, and
reduce its cost. In this paper we present a new method to
calculate the fluorescence efficiency (FE) of human cervical
tissue, based on in vivo measurements of 381 sites from 95
patients. This value is used in signal to noise ratio (SNR)
calculations to evaluate the performance of different
optical systems for detection of cervical pre-cancer. We
verify that the predicted SNR values, obtained using FE,
agree with the SNR of the patient's spectral data. We use
the resulting data to generate a receiver-operator
characteristic (ROC) curve that compares spectroscopy to the
current standard of care. Finally, preliminary results of
our economic analysis estimate that use of fluorescence
spectroscopy could save $2.1 billion annually in the
US.},
Key = {98034112829}
}
@article{5364713,
Author = {Ramanujam, N. and Burke, J.J. and Lifeng
Li},
Title = {Ferroelectric channel waveguides with high SHG conversion
efficiency and non-critical phasematching
characteristics},
Journal = {Proc. SPIE - Int. Soc. Opt. Eng. (USA)},
Volume = {2700},
Pages = {130 - 9},
Address = {San Jose, CA, USA},
Year = {1996},
Keywords = {ferroelectric devices;optical harmonic generation;optical
waveguide theory;optical waveguides;optimisation;},
Abstract = {Second harmonic generation (SHG) conversion efficiency in
quasi-phasematched (QPM) waveguides can be enhanced
significantly by optimizing the linear properties of the
guiding structure. We describe here a method for fast and
accurate computation of the modal properties of continuous,
periodically-poled, ferroelectric channel waveguides, and a
multi-parameter optimization algorithm which we have used to
increase normalized internal SHG conversion efficiency. We
will show, with results from our simulations, how both mode
confinement at the fundamental wavelength and overlap of the
transverse modes at the fundamental and second harmonic
wavelengths influence the SHG conversion efficiency.
Finally, we will also present the theoretical phasematching
characteristics of these designs, and discuss the
possibility of high SHG conversion efficiency
(2900%/W-cm<sup>2</sup>) near non-critically phasematched
regimes of operation},
Key = {5364713}
}
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