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University of Texas Southwest Medical Center
Quantitative Non-Contrast Perfusion using Arterial Spin Labeling for Assessment of Cancer Therapy Response
Ananth Madhuranthakam, Ph.D
Ananth.Madhuranthakam@UTSouthwestern.edu
Grant Number: U01 CA207091
Recent advances in the understanding of cancer biology have led to an increased number of cancer therapies. The evaluation of these new therapies in human clinical trials is associated with high cost and potential risks. Imaging approaches can play an important role in this evaluation by identifying patients who respond to treatments. The current radiological assessment of treatment outcomes, however, predominantly relies on the tumor size changes. This is a major limiting factor as the effects of many therapeutic agents at the microscopic level precede the eventual changes in tumor size. One such tumor property that has been extensively targeted for new cancer therapies is tumor angiogenesis (or perfusion), which has been shown to support tumor proliferation and infiltration. The team at UT Southwestern (UTSW) Medical Center, led by Dr. Madhuranthakam, has been developing a quantitative magnetic resonance imaging (MRI) technique that can measure tumor perfusion non-invasively and without the administration of any exogenous contrast agent. The arterial spin labeled (ASL) MRI technique uses highly permeable water as a tracer, by magnetically labeling the water protons in the arterial blood and measuring their accumulation in the tissue of interest. The UT SW team has used this technique to monitor therapy response in multiple clinical trials and have shown that ASL measured tumor perfusion decreased significantly in patients undergoing antiangiogenic therapy, much earlier than the tumor size changes. In the currently NIH-funded QIN project, the team endeavors to validate ASL measured perfusion as a quantitative imaging marker to evaluate early treatment response in patients with brain tumors (glioblastoma, GBM) and metastatic renal cell carcinoma (mRCC), two known highly vascularized tumors. They will also develop quality-controlled protocols to measure the reliability and precision of ASL measured flow using their novel 3D printed perfusion phantom, followed by brain and kidney perfusion in normal volunteers. The team will recruit GBM and mRCC patients from ongoing clinical trials at UTSW and will test the hypothesis that greater reduction in tumor perfusion compared to baseline immediately after treatment improves progression free survival and overall survival. Such early changes in ASL measured perfusion may predict tumor responsiveness better than anatomical imaging, thereby affecting patient management in a timely manner by changing treatments that may be ineffective and potentially toxic.
UT SW laboratory URL: http://www.utsouthwestern.edu/labs/madhuranthakam/
Reference:
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Wang X, Pirasteh A, Brugarolas J, Rofsky NM, Lenkinski RE, Pedrosa I, Madhuranthakam AJ. Whole-body MRI for metastatic cancer detection using T2 -weighted imaging with fat and fluid suppression. Magn Reson Med. 2018 Oct;80(4):1402-1415. doi: 10.1002/mrm.27117. Epub 2018 Feb 14. PMID: 29446127.
