Darren Roblyer
Boston University
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Featured researches published by Darren Roblyer.
Cancer Prevention Research | 2009
Darren Roblyer; Cristina Kurachi; Vanda M. Stepanek; Michelle D. Williams; Adel K. El-Naggar; J. Jack Lee; Ann M. Gillenwater; Rebecca Richards-Kortum
Although the oral cavity is easily accessible to inspection, patients with oral cancer most often present at a late stage, leading to high morbidity and mortality. Autofluorescence imaging has emerged as a promising technology to aid clinicians in screening for oral neoplasia and as an aid to resection, but current approaches rely on subjective interpretation. We present a new method to objectively delineate neoplastic oral mucosa using autofluorescence imaging. Autofluorescence images were obtained from 56 patients with oral lesions and 11 normal volunteers. From these images, 276 measurements from 159 unique regions of interest (ROI) sites corresponding to normal and confirmed neoplastic areas were identified. Data from ROIs in the first 46 subjects were used to develop a simple classification algorithm based on the ratio of red-to-green fluorescence; performance of this algorithm was then validated using data from the ROIs in the last 21 subjects. This algorithm was applied to patient images to create visual disease probability maps across the field of view. Histologic sections of resected tissue were used to validate the disease probability maps. The best discrimination between neoplastic and nonneoplastic areas was obtained at 405 nm excitation; normal tissue could be discriminated from dysplasia and invasive cancer with a 95.9% sensitivity and 96.2% specificity in the training set, and with a 100% sensitivity and 91.4% specificity in the validation set. Disease probability maps qualitatively agreed with both clinical impression and histology. Autofluorescence imaging coupled with objective image analysis provided a sensitive and noninvasive tool for the detection of oral neoplasia.
Journal of Biomedical Optics | 2008
Darren Roblyer; Rebecca Richards-Kortum; Konstantin Sokolov; Adel K. El-Naggar; Michelle D. Williams; Christine Kurachi; Anne Gillenwater
A multispectral digital microscope (MDM) is designed and constructed as a tool to improve detection of oral neoplasia. The MDM acquires in vivo images of oral tissue in fluorescence, narrow-band (NB) reflectance, and orthogonal polarized reflectance (OPR) modes, to enable evaluation of lesions that may not exhibit high contrast under standard white light illumination. The device rapidly captures image sequences so that the diagnostic value of each modality can be qualitatively and quantitatively evaluated alone and in combination. As part of a pilot clinical trial, images are acquired from normal volunteers and patients with precancerous and cancerous lesions. In normal subjects, the visibility of vasculature can be enhanced by tuning the reflectance illumination wavelength and polarization. In patients with histologically confirmed neoplasia, we observe decreased blue/green autofluorescence and increased red autofluorescence in lesions, and increased visibility of vasculature using NB and OPR imaging. The perceived lesion borders change with imaging modality, suggesting that multimodal imaging has the potential to provide additional diagnostic information not available using standard white light illumination or by using a single imaging mode alone.
Proceedings of the National Academy of Sciences of the United States of America | 2011
Darren Roblyer; Shigeto Ueda; Albert E. Cerussi; Wendy Tanamai; Amanda Durkin; Rita S. Mehta; David Hsiang; John Butler; Christine E. McLaren; Wen-Pin Chen; Bruce J. Tromberg
Approximately 8–20% of breast cancer patients receiving neoadjuvant chemotherapy fail to achieve a measurable response and endure toxic side effects without benefit. Most clinical and imaging measures of response are obtained several weeks after the start of therapy. Here, we report that functional hemodynamic and metabolic information acquired using a noninvasive optical imaging method on the first day after neoadjuvant chemotherapy treatment can discriminate nonresponding from responding patients. Diffuse optical spectroscopic imaging was used to measure absolute concentrations of oxyhemoglobin, deoxyhemoglobin, water, and lipid in tumor and normal breast tissue of 24 tumors in 23 patients with untreated primary breast cancer. Measurements were made before chemotherapy, on day 1 after the first infusion, and frequently during the first week of therapy. Various multidrug, multicycle regimens were used to treat patients. Diffuse optical spectroscopic imaging measurements were compared with final postsurgical pathologic response. A statistically significant increase, or flare, in oxyhemoglobin was observed in partial responding (n = 11) and pathologic complete responding tumors (n = 8) on day 1, whereas nonresponders (n = 5) showed no flare and a subsequent decrease in oxyhemoglobin on day 1. Oxyhemoglobin flare on day 1 was adequate to discriminate nonresponding tumors from responding tumors. Very early measures of chemotherapy response are clinically convenient and offer the potential to alter treatment strategies, resulting in improved patient outcomes.
Cancer Research | 2012
Shigeto Ueda; Darren Roblyer; Albert E. Cerussi; Amanda Durkin; Anais Leproux; Ylenia Santoro; Shanshan Xu; Thomas D. O'Sullivan; David Hsiang; Rita S. Mehta; John Butler; Bruce J. Tromberg
Tissue hemoglobin oxygen saturation (i.e., oxygenation) is a functional imaging endpoint that can reveal variations in tissue hypoxia, which may be predictive of pathologic response in subjects undergoing neoadjuvant chemotherapy. In this study, we used diffuse optical spectroscopic imaging (DOSI) to measure concentrations of oxyhemoglobin (ctO(2)Hb), deoxy-hemoglobin (ctHHb), total Hb (ctTHb = ctO(2)Hb + ctHHb), and oxygen saturation (stO(2) = ctO(2)Hb/ctTHb) in tumor and contralateral normal tissue from 41 patients with locally advanced primary breast cancer. Measurements were acquired before the start of neoadjuvant chemotherapy. Optically derived parameters were analyzed separately and in combination with clinical biomarkers to evaluate correlations with pathologic response. Discriminant analysis was conducted to determine the ability of optical and clinical biomarkers to classify subjects into response groups. Twelve (28.6%) of 42 tumors achieved pathologic complete response (pCR) and 30 (71.4%) were non-pCR. Tumor measurements in pCR subjects had higher stO(2) levels (median 77.8%) than those in non-pCR individuals (median 72.3%, P = 0.01). There were no significant differences in baseline ctO(2)Hb, ctHHb, and ctTHb between response groups. An optimal tumor oxygenation threshold of stO(2) = 76.7% was determined for pCR versus non-pCR (sensitivity = 75.0%, specificity = 73.3%). Multivariate discriminant analysis combining estrogen receptor staining and stO(2) further improved the classification of pCR versus non-pCR (sensitivity = 100%, specificity = 85.7%). These results show that elevated baseline tumor stO(2) are correlated with a pCR. Noninvasive DOSI scans combined with histopathology subtyping may aid in stratification of individual patients with breast cancer before neoadjuvant chemotherapy.
Head and Neck-journal for The Sciences and Specialties of The Head and Neck | 2012
Timothy J. Muldoon; Darren Roblyer; Michelle D. Williams; Vanda M. Stepanek; Rebecca Richards-Kortum; Ann M. Gillenwater
The purpose of this study was to evaluate the ability of high‐resolution microendoscopy to image and quantify changes in cellular and architectural features seen in early oral neoplasia in vivo.
Journal of Biomedical Optics | 2010
Timothy J. Muldoon; Nadhi Thekkek; Darren Roblyer; Dipen M. Maru; Noam Harpaz; Jonathan Z. Potack; Sharmila Anandasabapathy; Rebecca Richards-Kortum
Early detection of neoplasia in patients with Barretts esophagus is essential to improve outcomes. The aim of this ex vivo study was to evaluate the ability of high-resolution microendoscopic imaging and quantitative image analysis to identify neoplastic lesions in patients with Barretts esophagus. Nine patients with pathologically confirmed Barretts esophagus underwent endoscopic examination with biopsies or endoscopic mucosal resection. Resected fresh tissue was imaged with fiber bundle microendoscopy; images were analyzed by visual interpretation or by quantitative image analysis to predict whether the imaged sites were non-neoplastic or neoplastic. The best performing pair of quantitative features were chosen based on their ability to correctly classify the data into the two groups. Predictions were compared to the gold standard of histopathology. Subjective analysis of the images by expert clinicians achieved average sensitivity and specificity of 87% and 61%, respectively. The best performing quantitative classification algorithm relied on two image textural features and achieved a sensitivity and specificity of 87% and 85%, respectively. This ex vivo pilot trial demonstrates that quantitative analysis of images obtained with a simple microendoscope system can distinguish neoplasia in Barretts esophagus with good sensitivity and specificity when compared to histopathology and to subjective image interpretation.
Breast Cancer Research | 2013
Thomas D. O'Sullivan; Anais Leproux; Jeon-Hor Chen; Shadfar Bahri; Alex Matlock; Darren Roblyer; Christine E. McLaren; Wen-Pin Chen; Albert E. Cerussi; Min-Ying Su; Bruce J. Tromberg
IntroductionIn addition to being a risk factor for breast cancer, breast density has beenhypothesized to be a surrogate biomarker for predicting response toendocrine-based chemotherapies. The purpose of this study was to evaluate whethera noninvasive bedside scanner based on diffuse optical spectroscopic imaging(DOSI) provides quantitative metrics to measure and track changes in breast tissuecomposition and density. To access a broad range of densities in a limited patientpopulation, we performed optical measurements on the contralateral normal breastof patients before and during neoadjuvant chemotherapy (NAC). In this work, DOSIparameters, including tissue hemoglobin, water, and lipid concentrations, wereobtained and correlated with magnetic resonance imaging (MRI)-measuredfibroglandular tissue density. We evaluated how DOSI could be used to assessbreast density while gaining new insight into the impact of chemotherapy on breasttissue.MethodsThis was a retrospective study of 28 volunteers undergoing NAC treatment forbreast cancer. Both 3.0-T MRI and broadband DOSI (650 to 1,000 nm) were obtainedfrom the contralateral normal breast before and during NAC. Longitudinal DOSImeasurements were used to calculate breast tissue concentrations of oxygenated anddeoxygenated hemoglobin, water, and lipid. These values were compared withMRI-measured fibroglandular density before and during therapy.ResultsWater (r = 0.843; P < 0.001), deoxyhemoglobin (r =0.785; P = 0.003), and lipid (r = -0.707; P = 0.010)concentration measured with DOSI correlated strongly with MRI-measured densitybefore therapy. Mean DOSI parameters differed significantly between pre- andpostmenopausal subjects at baseline (water, P < 0.001;deoxyhemoglobin, P = 0.024; lipid, P = 0.006). During NACtreatment measured at about 90 days, significant reductions were observed inoxyhemoglobin for pre- (-20.0%; 95% confidence interval (CI), -32.7 to -7.4) andpostmenopausal subjects (-20.1%; 95% CI, -31.4 to -8.8), and water concentrationfor premenopausal subjects (-11.9%; 95% CI, -17.1 to -6.7) compared with baseline.Lipid increased slightly in premenopausal subjects (3.8%; 95% CI, 1.1 to 6.5), andwater increased slightly in postmenopausal subjects (4.4%; 95% CI, 0.1 to 8.6).Percentage change in water at the end of therapy compared with baseline correlatedstrongly with percentage change in MRI-measured density (r = 0.864; P = 0.012).ConclusionsDOSI functional measurements correlate with MRI fibroglandular density, bothbefore therapy and during NAC. Although from a limited patient dataset, theseresults suggest that DOSI may provide new functional indices of density based onhemoglobin and water that could be used at the bedside to assess response totherapy and evaluate disease risk.
Biomedical Optics Express | 2012
Albert E. Cerussi; Robert V. Warren; Brian Hill; Darren Roblyer; Ana s Leproux; Amanda Durkin; Thomas D. O'Sullivan; Sam Keene; Hosain Haghany; Timothy Quang; William M. Mantulin; Bruce J. Tromberg
Tissue simulating phantoms are an important part of instrumentation validation, standardization/training and clinical translation. Properly used, phantoms form the backbone of sound quality control procedures. We describe the development and testing of a series of optically turbid phantoms used in a multi-center American College of Radiology Imaging Network (ACRIN) clinical trial of Diffuse Optical Spectroscopic Imaging (DOSI). The ACRIN trial is designed to measure the response of breast tumors to neoadjuvant chemotherapy. Phantom measurements are used to determine absolute instrument response functions during each measurement session and assess both long and short-term operator and instrument reliability.
Head & Neck Oncology | 2010
Mohammed Rahman; Nilesh Ingole; Darren Roblyer; Vanda M. Stepanek; Rebecca Richards-Kortum; Ann M. Gillenwater; Surendra Shastri; Pankaj Chaturvedi
BackgroundThere is an important global need to improve early detection of oral cancer. Recent reports suggest that optical imaging technologies can aid in the identification of neoplastic lesions in the oral cavity; however, there is little data evaluating the use of optical imaging modalities in resource limited settings where oral cancer impacts patients disproportionately. In this article, we evaluate a simple, low-cost optical imaging system that is designed for early detection of oral cancer in resource limited settings. We report results of a clinical study conducted at Tata Memorial Hospital (TMH) in Mumbai, India using this system as a tool to improve detection of oral cancer and its precursors.MethodsReflectance images with white light illumination and fluorescence images with 455 nm excitation were obtained from 261 sites in the oral cavity from 76 patients and 90 sites in the oral cavity from 33 normal volunteers. Quantitative image features were used to develop classification algorithms to identify neoplastic tissue, using clinical diagnosis of expert observers as the gold standard.ResultsUsing the ratio of red to green autofluorescence, the algorithm identified tissues judged clinically to be cancer or clinically suspicious for neoplasia with a sensitivity of 90% and a specificity of 87%.ConclusionsResults suggest that the performance of this simple, objective low-cost system has potential to improve oral screening efforts, especially in low-resource settings.
Journal of Biomedical Optics | 2007
Nitin Nitin; David J. Javier; Darren Roblyer; Rebecca Richards-Kortum
Metallic nanoparticles have unique optical properties that can be exploited for molecular imaging in tissue. Image contrast depends on the nature of the particles, properties of the target tissue, and the imaging system. Maximizing image contrast for a particular application requires an understanding of the interplay of these factors. We demonstrate an approach that integrates the use of reflectance spectroscopy and imaging of particles in water and various tissue phantoms to evaluate the expected image contrast. We illustrate the application of this methodology for gold and silver nanospheres targeted against a biomarker expressed in epithelial tissue; predictions of contrast properties using diffuse reflectance spectroscopy were compared with widefield and high-resolution images of labeled tissue phantoms. The results show that the predicted image contrast based on spectroscopy agrees well with widefield and high-resolution imaging, and illustrate that gold and silver nanospheres at subnanomolar concentration are sufficient to produce contrast in both imaging modes. However, the effective contrast achieved with a particular type of nanoparticle can differ dramatically depending on the imaging modality. The ability to predict and optimize image contrast properties is a crucial step in the effective use of these nanomaterials for biomedical imaging applications.