Nimmi Ramanujam | Duke University (original) (raw)
Uploads
Papers by Nimmi Ramanujam
Molecular Cancer Therapeutics, 2013
PloS one, 2014
When monitoring response to cancer therapy, it is important to differentiate changes in glucose t... more When monitoring response to cancer therapy, it is important to differentiate changes in glucose tracer uptake caused by altered delivery versus a true metabolic shift. Here, we propose an optical imaging method to quantify glucose uptake and correct for in vivo delivery effects. Glucose uptake was measured using a fluorescent D-glucose derivative 2-(N-(7-Nitrobenz-2-oxa-1,3-diazol-4-yl)Amino)-2-deoxy-D-glucose (2-NBDG) in mice implanted with dorsal skin flap window chambers. Additionally, vascular oxygenation (SO2) was calculated using only endogenous hemoglobin contrast. Results showed that the delivery factor proposed for correction, "RD", reported on red blood cell velocity and injected 2-NBDG dose. Delivery-corrected 2-NBDG uptake (2-NBDG60/RD) inversely correlated with blood glucose in normal tissue, indicating sensitivity to glucose demand. We further applied our method in metastatic 4T1 and nonmetastatic 4T07 murine mammary adenocarcinomas. The ratio 2-NBDG60/RD was...
Journal of Biophotonics, 2014
Abbreviations: DR = diffuse reflectance, DRS = diffuse reflectance spectroscopy, μ a = absorption... more Abbreviations: DR = diffuse reflectance, DRS = diffuse reflectance spectroscopy, μ a = absorption coefficient μ s ′ = reduced scattering coefficient, μ s = scattering coefficient, λ = wavelength, ε = extinction coefficient, SDS = source-detector separation, PDT = photodynamic therapy, LUT = lookup table
Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual Conference, 2009
Diffuse reflectance spectroscopy of tissue allows quantification of underlying physiological and ... more Diffuse reflectance spectroscopy of tissue allows quantification of underlying physiological and morphological changes associated with cancer, provided that the absorption and scattering properties of the tissue can be effectively decoupled. A particular application of interest for tissue reflectance spectroscopy in the UV-VIS is intraoperative detection of residual cancer at the margins of excised breast tumors, which could prevent costly and unnecessary repeat surgeries. Our multi-disciplinary group has developed an optical imaging device, which employs a model-based algorithm for quantification of tissue optical properties, and is capable of surveying the entire specimen surface down to a depth of 1-2 mm, all within a short time as required for intraoperative use. In an ongoing IRB-approved study, reflectance spectral images were acquired from 55 margins in 48 patients. Conversion of the spectral images to quantitative tissue parameter maps was facilitated by a fast scalable inve...
The continuing morbidity and mortality rate related to cervical cancer necessitates an improvemen... more 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
Page 1. Monte Carlo based inverse model of diffuse reflectance for determination of UV-VIS optica... more Page 1. Monte Carlo based inverse model of diffuse reflectance for determination of UV-VIS optical properties and its application to breast cancer diagnosis Gregory M. Palmer, Quan Liu, and Nirmala Ramanujam Dept. BME, University of Wisconsin, 1550 Engineering Dr. Rm. ...
An angled fiber-optic probe enabling depth-sensitive fluorescence measurements was developed for ... more An angled fiber-optic probe enabling depth-sensitive fluorescence measurements was developed for enhancing epithelial pre-cancer detection. The probe was tested on solid, two-layered phantoms, and has been proven to be effective in selectively detecting fluorescence from ...
Neoplasia (New York, N.Y.), 2009
The feasibility of using quantitative diffuse reflectance spectroscopy to longitudinally monitor ... more 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 (<micro(s)'>). The tumor growth rates of the treated and control groups were nearly identical, as were changes in the scattering parameter <micro(s)'> during this time frame. However, tumors treated with DOX showed a transient but significant increase in blood oxygen saturati...
A method for estimating the optical properties of two-layered media (such as squamous epithelial ... more 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 (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;or=300 microm) 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 (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;or=1000 microm) 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 microm. 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.
Molecular Cancer Therapeutics, 2013
PloS one, 2014
When monitoring response to cancer therapy, it is important to differentiate changes in glucose t... more When monitoring response to cancer therapy, it is important to differentiate changes in glucose tracer uptake caused by altered delivery versus a true metabolic shift. Here, we propose an optical imaging method to quantify glucose uptake and correct for in vivo delivery effects. Glucose uptake was measured using a fluorescent D-glucose derivative 2-(N-(7-Nitrobenz-2-oxa-1,3-diazol-4-yl)Amino)-2-deoxy-D-glucose (2-NBDG) in mice implanted with dorsal skin flap window chambers. Additionally, vascular oxygenation (SO2) was calculated using only endogenous hemoglobin contrast. Results showed that the delivery factor proposed for correction, "RD", reported on red blood cell velocity and injected 2-NBDG dose. Delivery-corrected 2-NBDG uptake (2-NBDG60/RD) inversely correlated with blood glucose in normal tissue, indicating sensitivity to glucose demand. We further applied our method in metastatic 4T1 and nonmetastatic 4T07 murine mammary adenocarcinomas. The ratio 2-NBDG60/RD was...
Journal of Biophotonics, 2014
Abbreviations: DR = diffuse reflectance, DRS = diffuse reflectance spectroscopy, μ a = absorption... more Abbreviations: DR = diffuse reflectance, DRS = diffuse reflectance spectroscopy, μ a = absorption coefficient μ s ′ = reduced scattering coefficient, μ s = scattering coefficient, λ = wavelength, ε = extinction coefficient, SDS = source-detector separation, PDT = photodynamic therapy, LUT = lookup table
Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual Conference, 2009
Diffuse reflectance spectroscopy of tissue allows quantification of underlying physiological and ... more Diffuse reflectance spectroscopy of tissue allows quantification of underlying physiological and morphological changes associated with cancer, provided that the absorption and scattering properties of the tissue can be effectively decoupled. A particular application of interest for tissue reflectance spectroscopy in the UV-VIS is intraoperative detection of residual cancer at the margins of excised breast tumors, which could prevent costly and unnecessary repeat surgeries. Our multi-disciplinary group has developed an optical imaging device, which employs a model-based algorithm for quantification of tissue optical properties, and is capable of surveying the entire specimen surface down to a depth of 1-2 mm, all within a short time as required for intraoperative use. In an ongoing IRB-approved study, reflectance spectral images were acquired from 55 margins in 48 patients. Conversion of the spectral images to quantitative tissue parameter maps was facilitated by a fast scalable inve...
The continuing morbidity and mortality rate related to cervical cancer necessitates an improvemen... more 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
Page 1. Monte Carlo based inverse model of diffuse reflectance for determination of UV-VIS optica... more Page 1. Monte Carlo based inverse model of diffuse reflectance for determination of UV-VIS optical properties and its application to breast cancer diagnosis Gregory M. Palmer, Quan Liu, and Nirmala Ramanujam Dept. BME, University of Wisconsin, 1550 Engineering Dr. Rm. ...
An angled fiber-optic probe enabling depth-sensitive fluorescence measurements was developed for ... more An angled fiber-optic probe enabling depth-sensitive fluorescence measurements was developed for enhancing epithelial pre-cancer detection. The probe was tested on solid, two-layered phantoms, and has been proven to be effective in selectively detecting fluorescence from ...
Neoplasia (New York, N.Y.), 2009
The feasibility of using quantitative diffuse reflectance spectroscopy to longitudinally monitor ... more 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 (<micro(s)'>). The tumor growth rates of the treated and control groups were nearly identical, as were changes in the scattering parameter <micro(s)'> during this time frame. However, tumors treated with DOX showed a transient but significant increase in blood oxygen saturati...
A method for estimating the optical properties of two-layered media (such as squamous epithelial ... more 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 (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;or=300 microm) 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 (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;or=1000 microm) 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 microm. 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.