Colorectal cancer (CRC) is the second leading cause of cancer death in the United States. Metastasized colorectal cancer (mCRC), primarily in liver, is the predominate factor for the mortality of CRC patients. Treatment of CRC liver metastases is essential to the survival of mCRC patients. Currently, anti-angiogenesis therapy plays a significant role in the treatment of CRC liver metastases. Early and accurate prediction of response to anti-angiogenesis therapy is of vital clinical significance because: 1) early identification of nonresponders can expedite the adjustment of treatment regimens to avoid disease progression and spare patients from unnecessary toxicity and medical expense of ineffective therapies; 2) reliable response assessment can help individualize treatment strategy and optimize dose and time course of therapy to achieve maximal treatment efficacy; 3) an early and accurate predictive biomarker is also very beneficial to development of new therapy agents by providing a reliable surrogate endpoint for clinical trials. At present, however, a reliable treatment response assessment tool for anti-angiogenesis therapy does not exist clinically. To fill this gap, here we propose to develop a novel ultrasound microvessel imaging technology, VesselQuest, to early predict anti-angiogenesis therapy response by examining tumor micro-vasculature with quantitative hemodynamic and morphologic measurements. VesselQuest can accurately measure a wide dynamic range of microvessel flow speed and offers a spatial super-resolution that cannot be achieved by current clinical imaging modalities. Similar to other ultrasound techniques, VesselQuest is also noninvasive, safe, and cost effective. These features of VesselQuest provide excellent potential for clinical assessment of colorectal liver metastases treatment response to anti-angiogenic therapy.
Aims 1 and 2 of this study will be focused on technical development of VesselQuest, paving the way for the aims 3 and 4 of the study which will be focused on validating VesselQuest on an animal tumor model and conducting a pilot clinical study on CRC liver metastases patients to assess treatment response to anti-angiogenesis therapy. Successful completion of this project will provide a novel and viable technology for early prediction of anti-angiogenic therapy to improve treatment outcome and survival of CRC liver metastases patients. Technologies developed for this project can also be used for assessment of emerging novel treatment method such as immunotherapy.

Public Health Relevance

We will develop a novel ultrasound microvessel imaging technique with robust hemodynamic and morphologic measurements to assess anti-angiogenesis therapy response for colorectal cancer liver metastases. Successful completion of this project will provide a novel and viable technology for early prediction of anti-angiogenic therapy to improve treatment outcome and survival of colorectal liver metastases patients.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Career Transition Award (K99)
Project #
1K99CA214523-01
Application #
9284656
Study Section
Subcommittee I - Transition to Independence (NCI-I)
Program Officer
Radaev, Sergei
Project Start
2017-03-01
Project End
2019-02-28
Budget Start
2017-03-01
Budget End
2018-02-28
Support Year
1
Fiscal Year
2017
Total Cost
$166,384
Indirect Cost
$11,584
Name
Mayo Clinic, Rochester
Department
Type
Other Domestic Non-Profits
DUNS #
006471700
City
Rochester
State
MN
Country
United States
Zip Code
55905
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Song, Pengfei; Trzasko, Joshua D; Manduca, Armando et al. (2018) Improved Super-Resolution Ultrasound Microvessel Imaging With Spatiotemporal Nonlocal Means Filtering and Bipartite Graph-Based Microbubble Tracking. IEEE Trans Ultrason Ferroelectr Freq Control 65:149-167
Song, Pengfei; Manduca, Armando; Trzasko, Joshua D et al. (2017) Noise Equalization for Ultrafast Plane Wave Microvessel Imaging. IEEE Trans Ultrason Ferroelectr Freq Control 64:1776-1781
Gong, Ping; Song, Pengfei; Chen, Shigao (2017) Hadamard-Encoded Multipulses for Contrast-Enhanced Ultrasound Imaging. IEEE Trans Ultrason Ferroelectr Freq Control 64:1674-1683