University of Alabama at Birmingham

Disposable Perfusion Phantom for Accurate DCE-MRI Measurement of Pancreatic Cancer Therapy Response

Harrison Kim, Ph.D.
hyunkikim@uabmc.edu

Grant Number: UG3 CA232820-01A1

Dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) has been utilized to noninvasively assess early therapeutic responses in solid tumors by detecting changes in tumor perfusion prior to anatomic tumor shrinkage. Tumor response assessment in the early stage of therapy will enable to tailor and optimize treatment regimen for each patient. However, the measurement variability across different MRI scanners remains a major obstacle for multi-site clinical trials of quantitative DCE-MRI.

The UAB team recently developed a perfusion phantom named P4 (Point-of-care Portable Perfusion Phantom). The P4 can be imaged concurrently in the bore of a standard MRI scanner with a patient for real-time quality assurance. The P4 creates constant contrast enhancement curves with very robust repeatability, and thus contrast agent concentration time-course in a tumor, (which is a major source of errors in quantitating DCE-MRI parameters) can be accurately calculated in reference to the values observed in the phantom.

In this UG3/UH3 project, the team endeavors to test whether qDCE-MRI based analysis with the P4 can identify the early therapeutic response of pancreatic cancer in the neoadjuvant setting. Pancreatic cancer is typically associated with poor clinical outcomes. However, several newer treatment regimens have shown meaningful clinical benefit. Individual clinical benefit might be further improved with a patient stratification strategy based on early and accurate therapeutic response assessment. Pancreatic tumors are typically hypo-perfused, but the UAB team has recently demonstrated that the K^trans of pancreatic tumors favorably responding to chemotherapy increased 73±6% for 8 weeks, and that of non-responding tumors did not (0±5%) (p<0.0001) after P4-based error correction. Thus the change in tumor K^trans early in therapy is likely to serve as a robust surrogate biomarker that predicts pancreatic tumor response when MRI system-driven errors are corrected using the P4.

After successful completion of this study, the P4 and data analysis software package will be made publicly available to support clinical trials of various cancers in the abdomen. The team's developed technology will positively impact the care of cancer patients by a) improving accuracy in early assessment of therapy response, leading to better treatment decisions, and b) enabling data comparison across different MRI units and clinics, which will facilitate collaboration among institutes to develop advanced treatments.

Selected Publications:

Kim H., Morgan D. E., Schexnailder P., Navari R. M., Williams G. R., Rose J. B., Li Y., Paluri P., "Accurate Therapeutic Response Assessment of Pancreatic Ductal Adenocarcinoma using Quantitative DCE-MRI with a Point-of-Care Perfusion Phantom: A Pilot Study," Investigative Radiology, vol. 54, pp. 16-22, 2019.
Kim H., Mousa M., Schexnailder P., Hergenrother R., Bolding M., Vinoy T., Morgan D. E., "A portable perfusion phantom for quantitative DCE-MRI of the abdomen," Medical Physics, vol. 44, pp. 5198-5209, 2017. PMCID: PMC5646228
Kim H., Samuel S. L., Lopez-Casas P. P., Grizzle W. E., Hidalgo M., Kovar J., Oelschlager D. K., Zinn K. R., Warram J. M., Buchsbaum D. J., "SPARC independent delivery of nab-paclitaxel without depleting tumor stroma in patient-derived pancreatic cancer xenografts," Molecular Cancer Therapeutics, vol. 15, pp. 680-688, 2016. PMCID: PMC4873363
Kim H., "Modification of population based arterial input function to incorporate individual variation," Magnetic Resonance Imaging, vol. 45, pp. 66-71, 2018. PMCID: 5709187
Kim H., "Variability in Quantitative DCE-MRI: Sources and Solutions," Journal of Nature and Science, vol. 4, pii: e484, 2018.