The broad, long-term objective of this proposal is to improve the prognosis of patients with unresectable hepatocellular carcinoma (HCC). These patients commonly undergo transcatheter arterial embolization (TAE) as a form of palliative therapy. TAE is currently performed using x-ray DSA to estimate blood flow reductions after each injection of embolic material. However, DSA flow estimates may be highly subjective and poorly reflective of tumor perfusion. The objective of this proposal is to develop a new magnetic resonance imaging (MRI) technique to iteratively monitor liver tumor perfusion during TAE procedures. The proposed transcatheter intra-arterial perfusion MRI (TRIP-MRI) techniques offer the potential to monitor perfusion changes during TAE procedures within hybrid DSA/MRI procedure suites. For TRIP-MRI, small contrast doses are infused directly through the TAE catheter permitting iterative pharmacokinetic measurements to estimate perfusion changes after each injection of embolic material. Technical challenges must be resolved to permit serial quantitative TRIP-MRI measurements and further studies are required to validate TRIP-MRI measurements by comparison to invasive gold-standard methods. Proposed studies will address the following Specific Aims in a liver tumor animal model (Aims 1 and 2) and clinical patients with hepatocellular carcinoma (Aim 3):
Specific Aim 1 : Technical Development of TRIP-MRI Methodology Task 1: To test the hypothesis that intra-arterial injections permit quantitative estimation of contrast pharmacokinetics without needing to directly measure the arterial input function within distal hepatic arteries. Task 2: To test the hypothesis that TRIP-MRI contrast dose can be optimized intra-procedurally to permit short wash-out times and measurement repetition intervals conducive to TAE monitoring.
Specific Aim 2 : Quantitative Validation of TRIP-MRI Measurements Task 1: To test the hypothesis that TRIP-MRI measurements can accurately quantify intra-procedural perfusion reductions during liver tumor embolization. Task 2: To test the hypothesis that intra-procedural TRIP-MRI measurements can accurately predict the final fractional reduction to tumor perfusion after post-procedural catheter withdrawal.
Specific Aim 3 : Clinical Comparison of TRIP-MRI and DSA Monitored Embolic Endpoints Task 1: To test hypothesis that quantitative TRIP-MRI perfusion measurements provide a more reproducible estimation of TAE embolic endpoints than conventional DSA monitoring approaches. Task 2: To test the hypothesis that DSA flow estimates are poorly reflective of tumor perfusion reduction by comparison to quantitative intra-procedural TRIP-MRI perfusion measurements.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA134719-03
Application #
7802852
Study Section
Biomedical Imaging Technology Study Section (BMIT)
Program Officer
Tandon, Pushpa
Project Start
2008-07-01
Project End
2012-04-30
Budget Start
2010-05-01
Budget End
2012-04-30
Support Year
3
Fiscal Year
2010
Total Cost
$302,637
Indirect Cost
Name
Northwestern University at Chicago
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
005436803
City
Chicago
State
IL
Country
United States
Zip Code
60611
Li, Weiguo; Zhang, Zhuoli; Li, Kangan et al. (2015) Respiratory self-gating for free-breathing magnetization transfer MRI of the abdomen. Magn Reson Med 73:2249-54
Li, Kangan; Gordon, Andrew C; Zheng, Linfeng et al. (2015) Clinically applicable magnetic-labeling of natural killer cells for MRI of transcatheter delivery to liver tumors: preclinical validation for clinical translation. Nanomedicine (Lond) 10:1761-74
Zhang, Zhuoli; Li, Weiguo; Procissi, Daniele et al. (2015) Antigen-loaded dendritic cell migration: MR imaging in a pancreatic carcinoma model. Radiology 274:192-200
Zhang, Zhuoli; Li, Weiguo; Procissi, Daniel et al. (2014) Rapid dramatic alterations to the tumor microstructure in pancreatic cancer following irreversible electroporation ablation. Nanomedicine (Lond) 9:1181-92
Zhang, Yue; White, Sarah B; Nicolai, Jodi R et al. (2014) Multimodality imaging to assess immediate response to irreversible electroporation in a rat liver tumor model. Radiology 271:721-9
Zhang, Zhuoli; Procissi, Daniel; Li, Weiguo et al. (2013) High resolution MRI for non-invasive mouse lymph node mapping. J Immunol Methods 400-401:23-9
Yin, Xiaoming; Guo, Yang; Li, Weiguo et al. (2012) Chemical shift MR imaging methods for the quantification of transcatheter lipiodol delivery to the liver: preclinical feasibility studies in a rodent model. Radiology 263:714-22
Guo, Yang; Zhang, Yue; Jin, Ning et al. (2012) Electroporation-mediated transcatheter arterial chemoembolization in the rabbit VX2 liver tumor model. Invest Radiol 47:116-20
Li, Weiguo; Zhang, Zhuoli; Nicolai, Jodi et al. (2012) Magnetization transfer MRI in pancreatic cancer xenograft models. Magn Reson Med 68:1291-7
Guo, Yang; Jin, Ning; Klein, Rachel et al. (2012) Gas challenge-blood oxygen level-dependent (GC-BOLD) MRI in the rat Novikoff hepatoma model. Magn Reson Imaging 30:133-8

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