Thomas D O'Sullivan

Publications (21) View all

• Article: Optical imaging correlates with magnetic resonance imaging breast density and reveals composition changes during neoadjuvant chemotherapy.

  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
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  ABSTRACT: INTRODUCTION: In addition to being a risk factor for breast cancer, breast density has been hypothesized to be a surrogate biomarker for predicting response to endocrine-based chemotherapies. The purpose of this study was to evaluate whether a non-invasive bedside scanner based on diffuse optical spectroscopic imaging (DOSI) provides quantitative metrics to measure and track changes in breast tissue composition and density. In order to access a broad range of densities in a limited patient population, we performed optical measurements on the contralateral normal breast of patients before and during neoadjuvant chemotherapy (NAC). In this work, DOSI parameters, including tissue hemoglobin, water, and lipid concentrations were obtained and correlated with magnetic resonance imaging (MRI)-measured fibroglandular tissue density. We evaluate how DOSI could be used to assess breast density while gaining new insight into the impact of chemotherapy on breast tissue. METHODS: This was a retrospective study of 28 volunteers undergoing NAC treatment for breast cancer. 3.0T MRI and broadband DOSI (650-1000nm) were obtained from the contralateral normal breast before and during NAC. Longitudinal DOSI measurements were used to calculate breast tissue concentrations of oxygenated and deoxygenated hemoglobin, water, and lipid. These values were compared to MRI-measured fibroglandular density before and during therapy. RESULTS: Water (r=0.843, p<0.001), deoxyhemoglobin (r=0.785, p=0.003), and lipid (r=-0.707, p=0.010) concentration measured by DOSI correlated strongly with MRI-measured density prior to therapy. Mean DOSI parameters differed significantly between pre- and post-menopausal subjects at baseline (water: p<0.001, deoxyhemoglobin: p=0.024, lipid: p=0.006). During NAC treatment measured at ~90 days, significant reductions were observed in oxyhemoglobin for pre- (-20.0%, 95% confidence interval (CI): -32.7 to -7.4) and post-menopausal subjects (-20.1%, 95% CI: -31.4 to -8.8), and water concentration for pre-menopausal subjects (-11.9%, 95% CI: -17.1 to -6.7) compared to baseline. Lipid increased slightly in pre-menopausal subjects (3.8%, 95% CI: 1.1 to 6.5) and water increased slightly in post-menopausal subjects (4.4%, 95% CI: 0.1 to 8.6). Percent change in water at the end of therapy compared to baseline correlated strongly with percent change in MRI-measured density (r=0.864, p=0.012). CONCLUSIONS: DOSI functional measurements correlate with MRI fibroglandular density, both prior to therapy and during NAC. Though a limited patient data set, these results suggest that DOSI may provide new functional indices of density based on hemoglobin and water that could be used at the bedside to assess response to therapy and evaluate disease risk.
  Breast cancer research: BCR 02/2013; 15(1):R14. · 5.24 Impact Factor
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  Available from: Thomas D O'Sullivan

  Article: Continuous sensing of tumor-targeted molecular probes with a vertical cavity surface emitting laser-based biosensor.

  Natesh Parashurama, Thomas D O'Sullivan, Adam De La Zerda, Pascale El Kalassi, Seongjae Cho, Hongguang Liu, Robert Teed, Hart Levy, Jarrett Rosenberg, Zhen Cheng, Ofer Levi, James S Harris, Sanjiv S Gambhir
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  ABSTRACT: Molecular optical imaging is a widespread technique for interrogating molecular events in living subjects. However, current approaches preclude long-term, continuous measurements in awake, mobile subjects, a strategy crucial in several medical conditions. Consequently, we designed a novel, lightweight miniature biosensor for in vivo continuous optical sensing. The biosensor contains an enclosed vertical-cavity surface-emitting semiconductor laser and an adjacent pair of near-infrared optically filtered detectors. We employed two sensors (dual sensing) to simultaneously interrogate normal and diseased tumor sites. Having established the sensors are precise with phantom and in vivo studies, we performed dual, continuous sensing in tumor (human glioblastoma cells) bearing mice using the targeted molecular probe cRGD-Cy5.5, which targets αVβ3 cell surface integrins in both tumor neovasculature and tumor. The sensors capture the dynamic time-activity curve of the targeted molecular probe. The average tumor to background ratio after signal calibration for cRGD-Cy5.5 injection is approximately 2.43±0.95 at 1 h and 3.64±1.38 at 2 h (N=5 mice), consistent with data obtained with a cooled charge coupled device camera. We conclude that our novel, portable, precise biosensor can be used to evaluate both kinetics and steady state levels of molecular probes in various disease applications.
  Journal of Biomedical Optics 11/2012; 17(11):117004. · 3.16 Impact Factor
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  Available from: Albert Cerussi

  Article: Baseline tumor oxygen saturation correlates with a pathologic complete response in breast cancer patients undergoing neoadjuvant chemotherapy.

  Shigeto Ueda, Darren Roblyer, Albert Cerussi, Amanda Durkin, Anais Leproux, Ylenia Santoro, Shanshan Xu, Thomas D O'Sullivan, David Hsiang, Rita Mehta, John Butler, Bruce J Tromberg
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  ABSTRACT: 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.
  Cancer Research 07/2012; 72(17):4318-28. · 7.86 Impact Factor
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  Available from: Thomas D O'Sullivan

  Article: Diffuse optical imaging using spatially and temporally modulated light.

  Thomas D O'Sullivan, Albert E Cerussi, David J Cuccia, Bruce J Tromberg
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  ABSTRACT: The authors describe the development of diffuse optical imaging (DOI) technologies, specifically the use of spatial and temporal modulation to control near infrared light propagation in thick tissues. We present theory and methods of DOI focusing on model-based techniques for quantitative, in vivo measurements of endogenous tissue absorption and scattering properties. We specifically emphasize the common conceptual framework of the scalar photon density wave for both temporal and spatial frequency-domain approaches. After presenting the history, theoretical foundation, and instrumentation related to these methods, we provide a brief review of clinical and preclinical applications from our research as well as our outlook on the future of DOI technology.
  Journal of Biomedical Optics 07/2012; 17(7):071311. · 3.16 Impact Factor
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  Available from: Thomas D O'Sullivan

  Article: Tissue phantoms in multicenter clinical trials for diffuse optical technologies.

  Albert E Cerussi, Robert Warren, Brian Hill, Darren Roblyer, Anaїs Leproux, Amanda F Durkin, Thomas D O'Sullivan, Sam Keene, Hosain Haghany, Timothy Quang, William M Mantulin, Bruce J Tromberg
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  ABSTRACT: 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.
  Biomedical Optics Express 05/2012; 3(5):966-71. · 2.33 Impact Factor