SBIR-STTR Award

Angiogenesis and hypoxia can significantly influence the efficacy of therapy and the behavior of surviving tumor cells. This important fact is supported by a vast amount of literature on pre-clinical models and clinical studies. There is growing demand for technologies to measure tumor hypoxia and angiogenesis temporally and spatially in vivo to enable advances in drug screening, development and optimization. This is particularly useful in the emerging era of anti-angiogenesis and anti-hypoxia therapies. We propose to develop a portable, low power consumption and low-cost, yet accurate and reliable, multimodality optical spectroscopy system with a novel fiber-optic probe to dynamically characterize tumor hypoxia, angiogenesis, and metabolism as well as tissue drug concentration in small animal models without operator bias. The multimodality optical spectroscopy system will be a laptop or battery powered console with the integration of multiple LEDs, a dual-channel spectrometer, a fiber optic probe, electronics and custom software that can be used to perform both diffuse reflectance and fluorescence spectroscopy in vivo. The fiber-optic probe will include an interferometric pressure sensor that can be used to control the probe-tissue pressure for reliable and reproducible spectroscopic measurement of tissue optical properties. The aims of the proposed work (Phase I) will be to (1) design the core technology using LEDs and an interferometric fiber-optic sensor, (2) characterize its performance metrics and (3) validate its utility in a pre-clinical mammary tumor model. This technology will be extended to include quantitative fluorescence measurements in the Phase II STTR project period along with different probe designs to provide flexibility in implementation of this technology to ectopic (tumors grown on flank) and orthotopic models. The commercial device can be marketed as either a single- modality (diffuse reflectance) or a multi-modality (reflectance and fluorescence) device. The outcome of Phase I will lead to a 1st generation Quantilux device which can be productized while the multi-modality 2nd generation device is being refined.The overall objective in Phase II and beyond will be to develop a marketable version of the device and validate its utility for longitudinal tumor therapy monitoring in mouse tumor models.

Public Health Relevance:
Our long-term goal is to develop and commercialize a compact, low power consumption, low-cost, yet accurate and reliable, optical spectroscopy system, to dynamically and non-destructively quantify tumor physiological and morphological endpoints such as angiogenesis and hypoxia in small animal models. This proposal is significantly relevant to public health because angiogenesis and hypoxia can significantly influence the efficacy of therapy and the behavior of surviving tumor cells.

Public Health Relevance Statement:
Our long-term goal is to develop and commercialize a compact, low power consumption, low-cost, yet accurate and reliable, optical spectroscopy system, to dynamically and non-destructively quantify tumor physiological and morphological endpoints such as angiogenesis and hypoxia in small animal models. This proposal is significantly relevant to public health because angiogenesis and hypoxia can significantly influence the efficacy of therapy and the behavior of surviving tumor cells.

NIH Spending Category:
Bioengineering; Breast Cancer; Cancer; Networking and Information Technology R&D

Project Terms:
absorption; Affect; angiogenesis; Animal Model; Animals; antiangiogenesis therapy; base; Behavior Therapy; Blood Vessels; Breast Cancer Model; Calibration; cancer therapy; charge coupled device camera; Clinical Research; Computer software; Computers; Consumption; cost; Coupling; Custom; design; design and construction; Detection; detector; Development; Devices; Diffuse; Electronics; Feedback; Fiber Optics; flexibility; Fluorescence; Fluorescence Spectroscopy; Gases; Generations; Goals; Hemoglobin; Hypoxia; in vivo; instrument; laptop; Lead; Light; Literature; Mammary Neoplasms; Marketing; Measurement; Measures; Metabolism; Metric; Mitochondria; Modality; Modeling; Monitor; multimodality; Mus; neoplastic cell; Noise; novel; optical sensor; Optics; Outcome; Oxidation-Reduction; Oxygen; Performance; Pharmaceutical Preparations; Phase; photomultiplier; Physiological; Physiology; Positioning Attribute; pre-clinical; Pre-Clinical Model; Preclinical Drug Evaluation; pressure; programs; Property; public health medicine (field); research clinical testing; Resolution; response; sensor; Skin; Small Business Technology Transfer Research; Source; Spectrum Analysis; Surface; System; Techniques; Technology; Testing; Time; tissue phantom; Tissues; Treatment Efficacy; Tube; tumor; Variant; voltage; Work

In 2008, there were 47,560 new cases of head and neck cancers (HNC) in the United States. Early detection of new and locally recurrent cancers is clinically important to reduce not only cancer related mortality, but also treatment associated morbidity as it impacts multiple organ functions including respiration, olfaction, hearing, eating, swallowing, and speaking. Discrimination of cancer from non-malignant tissues is dependent on pathological examination of lesion biopsies. Although these lesions are identified during an initial clinical exam, obtaining a specimen for analysis can be technically challenging and uncomfortable for patients. Furthermore, there is an immense amount of labor, facility, and monetary resources that are expended on patients who ultimately have no malignancy. Once carcinoma is identified, treatment for advanced HNC commonly requires a combination of surgery, radiation, and chemotherapy to maximize the chance for cure. Multi-modality treatment causes undesirable side effects that affect a patient's physical well-being, e.g. eating and speaking, and quality of life. Using fewer modalities can minimize morbidity but with a potentially increased risk for treatment failure. Determination of the optimal strategy to both minimize morbidity and optimize the chance for cure is a major clinical challenge. There is a significant unmet clinical need associated with the screening and treatment of head and neck cancers. Our long-term goal is to develop a portable, optical technology that can provide accurate and precise analysis of tissue absorption and scattering of local tissue sites guided by white light and auto fluorescence imaging. The initial market will be applications related to the diagnosis and guided therapy of head and neck cancers. The clinical value of this tool would require it to be fast and non- invasive such that feedback could be obtained during the patient's visit, portable such that it can be used in an ambulatory setting and quantitative with minimal operator bias such that data obtained is consistent across operators and patients.

Public Health Relevance Statement:


Public Health Relevance:
Our long-term goal is to develop and commercialize a portable, optical technology that can provide accurate and precise analysis of tissue absorption and scattering of local tissue sites guided by white light and auto fluorescence imaging for the diagnosis and guided therapy of head and neck cancers. There is lack of a tool that can be routinely applied to assess diagnostically and therapeutically relevant endpoints in HNSCC therefore this grant is significantly related to public health for its potential to improve the diagnosis and treatment of HNSCC.

Project Terms:
absorption; Administrative Supplement; Adverse effects; Affect; Biopsy; Blood Vessels; Calibration; Carcinoma; chemotherapy; Clinical; clinical Diagnosis; Computer software; cost; Data; Deglutition; design; Devices; Diagnosis; Diffuse; Discrimination (Psychology); Early Diagnosis; Eating; Feedback; Figs - dietary; fluorescence imaging; Funding; Goals; Grant; Head and Neck Cancer; Head and Neck Squamous Cell Carcinoma; Hearing; Image; improved; Individual; Lesion; Light; Malignant Neoplasms; Marketing; Measurement; Measures; Modality; Modeling; Monitor; Morbidity - disease rate; Mortality Vital Statistics; Motor; motor control; Movement; Non-Malignant; Operative Surgical Procedures; optical sensor; Optics; Oral mucous membrane structure; Organ; Outcome; Patients; PC3 cell line; Personal Satisfaction; Phase; Physiology; pre-clinical; Pre-Clinical Model; pressure; Property; public health medicine (field); public health relevance; Publishing; Quality of life; Radiation therapy; Radiosurgery; Recurrent Malignant Neoplasm; research clinical testing; Resources; Respiration; response; Risk; Sampling; screening; sensor; Site; Small Business Technology Transfer Research; Smell Perception; Source; Specimen; Spectrum Analysis; Surgeon; System; Technology; Testing; Therapeutic; tissue phantom; Tissues; tool; Treatment Failure; tumor; United States; Visit; Work