Fast phosphorus-31 magnetic resonance spectroscopic imaging of the liver: Clinical implementation and applications in post-radiation therapy
Abstract
The main objective of the presented dissertation is to make phosphorus 31 (31P) magnetic resonance spectroscopy (MRS) a clinically practical tool to evaluate metabolic changes in liver diseases for diagnosis and/or post-treatment monitoring. Liver metabolism correlates with inflammatory and neoplastic liver diseases, which alter the intracellular concentration of 31P metabolites. It is assumed that such metabolic changes occur prior to structural, morphological changes of the tissue. Therefore, information on regional changes of 31P metabolites in the liver, as obtained by magnetic resonance spectroscopic imaging (MRSI) can help in diagnosis and follow-up of various liver diseases. Specifically, we see an immediate need of this technology in the follow-up of hepatocellular carcinoma (HCC) patients treated with selective internal radiation therapy (SIRT) with Yttrium 90 (90Y) and stereotactic body radiation therapy (SBRT), two emerging targeted radiation therapy techniques for HCC treatment. Current treatment monitoring approaches based on changes in tumor size give ambiguous results within the first six months of these treatments. Since the life expectancy with progressive liver cancer is only in the order of 6 months to 1 year, it is crucial to find tools for assessing early treatment response. Metabolic information available through 31P MRSI, providing localized information regarding liver metabolism, could be a sensitive tool for both, diagnosis as well as treatment monitoring in focal liver disease. To date, 31P MRS suffers from several disadvantages, which limit its use in the clinical setting. Two of these limitations are limited anatomical coverage of 31P coils and the long scan times of 31P MRSI protocols. So far mostly single-channel surface coils have been available for 31P MRS studies, suffering from limited sensitivity in deeper tissue. Therefore, surface coils cannot be used very efficiently for spectroscopic data acquisition of a focal disease or multiple metastases. This dissertation was aimed at designing and testing a new dual-tuned 31P/1H coil array that can overcome the limitations of the existing surface coils: (a) allow coverage of the entire abdomen for 31P liver spectroscopy, (b) enable the acquisition of high-quality 1H images without repositioning the patient, and (c) provide potential for the development of fast 31P spectroscopy acquisition schemes, such as GRAPPA (GeneRalized Autocalibrating Partially Parallel Acquisition), to significantly reduce the long scan time. Furthermore, a clinical study was designed to validate the efficacy of the coil and associated technical developments in the clinic. It was successfully demonstrated that 31P MRSI is more sensitive to changes in the lesions than conventional imaging techniques. Successful validation of the multi-channel dual-tuned phased-array coil, for the first time allowed monitoring tumors located in deep tissue or assess multi-focal tumor in the same scan. Successful implementation of GRAPPA acquisition technique reduced 2D 31P MRSI data acquisition time by two-fold and allowed for better integration of 31P spectroscopy in the clinic. In addition, it opens the possibility for enabling 3D 31P MRSI techniques within reasonable scan times while further improving the 31P MRSI acquisition coverage. The ultimate goal of the dissertation was to ensure that the techniques and methods developed as part of this work can be immediately used in the clinic to benefit patient care. The ability to assess changes in 31 P metabolite ratios in the HCC patients validates 31P MRSI as a potential clinical tool to predict the response of liver cancer to targeted therapy much earlier than conventional monitoring techniques. Since a therapy is not changed before the treatment response is assessed, early treatment prognosis using 31P MRSI will have significant impact to improve patient care. Finally, having a clinically established 31P spectroscopic technique now allows for extending the benefits of 31P spectroscopy in diagnosis and follow-up of diseases to other organs and tissue, and to other targeted therapies.
Degree
Ph.D.
Advisors
Dydak, Purdue University.
Subject Area
Biomedical engineering|Health sciences|Medical imaging|Oncology
Off-Campus Purdue Users:
To access this dissertation, please log in to our
proxy server.