Treatment with radiation or chemo-radiotherapy is the standard therapy for head and neck cancers but this treatment is well known to be less efficacious in patients with hypoxic tumors. Furthermore, cancer therapy may alter tumor physiological status, thus impacting treatment efficacy. Factors that modulate tumor oxygenation include blood flow, blood oxygenation, oxygen metabolism, and nicotine levels (i.e., tobacco use). Tumor hemodynamics and metabolism, however, are not routinely measured during cancer therapy due to the lack of appropriate technologies. Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) are the best currently available and reproducible methods to measure target lesions selected for objective response assessment, but these modalities require large and costly instrumentation that severely limits their routine use in clinics. The capabilities of diffuse optics for continuously monitoring tumor hemodynamics and metabolism during therapy at the clinical bedside have recently been demonstrated in our preliminary studies. The objective of this project is to develop and optimize a noninvasive versatile multi-modality clinical optical instrument to aid in evaluating and predicting tumor responses at the most early stage possible. More specifically, this optical instrument will monitor and predict hemodynamic and metabolic responses to chemo- radiotherapy in head and neck tumors. We hypothesize that functional assessment of tumor physiological status and dynamic changes during therapy will provide information for early prediction of long-term treatment outcomes, thus enabling clinicians to optimize therapy for each patient in a time sensitive fashion. To achieve this goal, we will assemble a hybrid flow and oxygen system that combines a newly developed diffuse correlation spectroscopy (DCS) flowmeter with a commercial tissue-oximeter for simultaneous measurement of tumor blood flow, oxygenation, and oxygen metabolism (derived from the flow and oxygenation data). The instrument including optical probes and a software platform will be tested and optimized for continuous and longitudinal monitoring of tumor physiological status and hemodynamic/metabolic changes before, during and after therapy in patients including smokers and nonsmokers (n=125). It is anticipated that significant correlations will be observed between therapy outcomes (e.g., tumor volume change, tumor toxicity, time to disease recurrence, survival) and tumor physiological status and changes as well as nicotine levels. Different types of physiological parameters may show different sensitivities to cancer therapy in each patient, which could reveal the primary factor(s) affecting individual therapy outcomes. Our novel hybrid optical system will provide hemodynamic and metabolic imaging contrasts complementary to those of CT and MRI, and holds unique potential for early evaluating and predicting cancer therapy responses. Our long-term goal is to develop robust scientific collaborations to optimize and individualize cancer therapy at early stages with noninvasive optical technologies.

Public Health Relevance

Treatment with radiation alone or in combination with chemotherapy is standard therapy for the head and neck cancers, but this treatment is well known to be less efficacious in patients with poorly-vascularized/hypoxic tumors. The objective of this project is to develop and test a low-cost clinical-level optical instrument that can quickly assess tumor hemodynamic and metabolic status and responses to cancer therapy in the early stages. This in depth assessment of tumor hemodynamic and metabolic properties will provide essential information for the early prediction and evaluation of treatment outcomes, thus enabling clinicians to optimize individual treatment.

Agency
National Institute of Health (NIH)
Type
Research Project (R01)
Project #
5R01CA149274-05
Application #
8657873
Study Section
Biomedical Imaging Technology Study Section (BMIT)
Program Officer
Baker, Houston
Project Start
Project End
Budget Start
Budget End
Support Year
5
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of Kentucky
Department
Biomedical Engineering
Type
Graduate Schools
DUNS #
City
Lexington
State
KY
Country
United States
Zip Code
40506
Huang, Chong; Seong, Myeongsu; Morgan, Joshua Paul et al. (2016) Low-cost compact diffuse speckle contrast flowmeter using small laser diode and bare charge-coupled-device. J Biomed Opt 21:80501
Dong, Lixin; Kudrimoti, Mahesh; Irwin, Daniel et al. (2016) Diffuse optical measurements of head and neck tumor hemodynamics for early prediction of chemoradiation therapy outcomes. J Biomed Opt 21:85004
Huang, Chong; Irwin, Daniel; Lin, Yu et al. (2015) Speckle contrast diffuse correlation tomography of complex turbid medium flow. Med Phys 42:4000-6
Huang, Chong; Radabaugh, Jeffrey P; Aouad, Rony K et al. (2015) Noncontact diffuse optical assessment of blood flow changes in head and neck free tissue transfer flaps. J Biomed Opt 20:075008
Huang, Chong; Lin, Yu; He, Lian et al. (2015) Alignment of sources and detectors on breast surface for noncontact diffuse correlation tomography of breast tumors. Appl Opt 54:8808-16
He, Lian; Lin, Yu; Huang, Chong et al. (2015) Noncontact diffuse correlation tomography of human breast tumor. J Biomed Opt 20:86003
Cheng, Ran; Shang, Yu; Wang, Siqi et al. (2014) Near-infrared diffuse optical monitoring of cerebral blood flow and oxygenation for the prediction of vasovagal syncope. J Biomed Opt 19:17001
Shang, Yu; Gurley, Katelyn; Yu, Guoqiang (2013) Diffuse Correlation Spectroscopy (DCS) for Assessment of Tissue Blood Flow in Skeletal Muscle: Recent Progress. Anat Physiol 3:128
Li, Ting; Lin, Yu; Shang, Yu et al. (2013) Simultaneous measurement of deep tissue blood flow and oxygenation using noncontact diffuse correlation spectroscopy flow-oximeter. Sci Rep 3:1358
He, Lian; Lin, Yu; Shang, Yu et al. (2013) Using optical fibers with different modes to improve the signal-to-noise ratio of diffuse correlation spectroscopy flow-oximeter measurements. J Biomed Opt 18:037001

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