My long-range goal is to assess and improve the capability of diffuse optical methods in detection, diagnosis and therapeutic monitoring of breast cancer. Diffuse optical methods using near-infrared light provide several unique functional parameters (such as total hemoglobin concentration, blood oxygen saturation, blood flow, water and lipid concentrations) to enhance tumor sensitivity and specificity. Moreover, deep tissue micro-environment (e.g. vascular leakiness, glucose metabolism) can be probed with diffuse fluorescence imaging/spectroscopy. Diffuse optical methods can impact cancer therapy monitoring and planning at early stages since the metabolic changes due to therapy may precede the anatomical size changes. During the mentored K99 phase, I explored the utility of portable diffuse optical device to assess neoadjuvant chemotherapy response of human subjects with breast cancer, and received trainings in tumor biology, biostatistics and biomedical imaging. The proposed research builds on initial success from K99 phase and aims to expand the monitoring capability of dffuse optics by incorporating fluorescence detection. Using new targeted optical fluorescent dyes, one can probe tumor specific metabolism and physiology not accessible by endogenous contrast alone. In particular, I will explore deoxyglucose analogue fluorescent dye to test its ability to probe glucose metabolism, which has been successfully utilized in PET imaging for therapy monitoring and diagnosis. First, I will build preclinical study platform consisting of animal tumor models and diffuse optical imaging/spectroscopy systems to quantify both endogenous and exogenous tumor contrast accurately. The fluorescent dye will be characterized for its biodistribution, pharmacokinetics, and tumor-to-normal contrast in mouse xenograft model by microscopic and macroscopic fluorescence imaging techniques, and will be compared to autoradiography and PET. Then, I will investigate whether simultaneous monitoring of glucose and oxygen metabolism accessible by all optical methods can enhance the assessment of treatment efficacy. This research will pave the ways for molecular imaging in vivo for therapy monitoring when it becomes available for human use.

Public Health Relevance

Early prediction of patient response to breast cancer therapies is crucial for non-responders to avoid ineffective toxic therapy and move to alternative treatment quickly. Diffuse optical methods have potential for early prediction since they are sensitive to therapy-induced metabolism changes. The goal of this proposal is to assess and improve the capability of diffuse optical methods for individualized therapy monitoring.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Transition Award (R00)
Project #
5R00CA126187-04
Application #
8239498
Study Section
Special Emphasis Panel (NSS)
Program Officer
Tandon, Pushpa
Project Start
2008-09-08
Project End
2014-03-31
Budget Start
2012-04-01
Budget End
2013-03-31
Support Year
4
Fiscal Year
2012
Total Cost
$241,529
Indirect Cost
$50,983
Name
University of Rochester
Department
Biomedical Engineering
Type
Schools of Engineering
DUNS #
041294109
City
Rochester
State
NY
Country
United States
Zip Code
14627
Ban, H Y; Schweiger, M; Kavuri, V C et al. (2016) Heterodyne frequency-domain multispectral diffuse optical tomography of breast cancer in the parallel-plane transmission geometry. Med Phys 43:4383
Ramirez, Gabriel; Proctor, Ashley R; Jung, Ki Won et al. (2016) Chemotherapeutic drug-specific alteration of microvascular blood flow in murine breast cancer as measured by diffuse correlation spectroscopy. Biomed Opt Express 7:3610-3630
Chung, So Hyun; Feldman, Michael D; Martinez, Daniel et al. (2015) Macroscopic optical physiological parameters correlate with microscopic proliferation and vessel area breast cancer signatures. Breast Cancer Res 17:72
Han, Songfeng; Johansson, Johannes; Mireles, Miguel et al. (2015) Non-contact scanning diffuse correlation tomography system for three-dimensional blood flow imaging in a murine bone graft model. Biomed Opt Express 6:2695-712
Han, Songfeng; Hoffman, Michael D; Proctor, Ashley R et al. (2015) Non-Invasive Monitoring of Temporal and Spatial Blood Flow during Bone Graft Healing Using Diffuse Correlation Spectroscopy. PLoS One 10:e0143891
Busch, David R; Choe, Regine; Durduran, Turgut et al. (2014) Blood flow reduction in breast tissue due to mammographic compression. Acad Radiol 21:151-61
Choe, Regine; Putt, Mary E; Carlile, Peter M et al. (2014) Optically measured microvascular blood flow contrast of malignant breast tumors. PLoS One 9:e99683
Xu, He N; Mir, Tahreem A; Lee, Seung-Cheol et al. (2013) Mapping the redox state of CHOP-treated non-Hodgkin's lymphoma xenografts in mice. Adv Exp Med Biol 789:243-9
Busch, David R; Choe, Regine; Durduran, Turgut et al. (2013) Towards non-invasive characterization of breast cancer and cancer metabolism with diffuse optics. PET Clin 8:
Busch, David R; Choe, Regine; Rosen, Mark A et al. (2013) Optical malignancy parameters for monitoring progression of breast cancer neoadjuvant chemotherapy. Biomed Opt Express 4:105-21

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