Enabling clinical tissue microstructure imaging as a diagnostic tool in wide-bore 3T MRI

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PROJECT SUMMARY/ABSTRACT Definitive characterization of cytoarchitecture and its alternation is key to clinical diagnosis and patient management in disease, including cancer. Current standard-of-care of such microstructure characterization is based primarily on histopathological assessment via biopsy sampling of suspected lesions. However, invasive biopsy procedures carry burdens of procedure complexity, sampling errors, and complications. Thus, it is desirable to have a non-invasive, high-sensitivity, high-specificity imaging tool that accurately assesses tumor microstructures that are comparable to that obtained from biopsy/histopathology. This will have the clinically significant result of reducing unnecessary biopsies at the minimum, and perhaps reduce the overall number of biopsy procedures and repeat biopsies. Furthermore, this will significantly improve the precision of biopsy to sample clinically significant cancers and regions most relevant to cancer prognosis. We propose to apply advanced diffusion MRI (dMRI), including novel oscillating gradient spin echo (OGSE) diffusion encoding, for tumor microstructure imaging and the pilot application will be to improve characterization of the epithelium, stroma, and lumen volume fractions which are highly correlated to prostate cancer grades. OGSE dMRI has been attempted in clinical whole-body MRI but the technique has had only modest success due to the limited gradient performance of whole-body MRI scanners. The gradient amplitude and slew rate of existing clinical whole-body 3.0T MRI scanners are often constrained by peak power of the gradient driver. Many clinical 70- cm wide-bore MRI systems operate at 1 MVA peak power, while some high-end systems increase the peak power to 2-2.7 MVA. However, the 2-3X higher peak power substantially increases the overall cost of MRI systems and requires major increases to the hospital's electrical service and cooling infrastructure to accommodate increased electrical power and thermal loads. Consequently, such upgrades become cost prohibitive and are impractical for wide adoption. Our technical solution is to build a new 4 MVA silicon carbide (SiC) semiconductor gradient driver which replaces a conventional silicon 1 MVA or 2 MVA gradient driver in clinical 3.0T wide-bore MRI scanners without requiring any changes to facility infrastructure. We have assembled a diverse, multi-disciplinary team from GE Research, Memorial Sloan Kettering Cancer Center, and Stanford University to develop MRI tools and methods to address clinical needs of non-invasive tumor microstructure imaging to solve clinically significant problems in cancer. We will demonstrate tumor microstructure imaging enabled by higher gradient amplitude and slew rate can provide clinical diagnostic information on tumor characterization comparable to that obtained from biopsy and move closer to the goal of reducing unnecessary biopsies. We will demonstrate the clinical significance in prostate cancer, as it is the second leading cause of death in men. It is applicable to other cancers and a broad range of clinical applications where non-invasive tumor microstructure characterization will significantly improve patient management.