Time reveals length scale: human tissue microstructure characterization by time-dependent diffusion MR

Diagnosing disease at early stage of its progression critically depends on the detection of tissue structural changes at short length scale. For example, tumor cell proliferation is the hallmark of cancer, and the detection in standard-of-care is via biopsy. However, the invasive nature and sampling error of biopsy prohibit its wide use. MRI frequently reveals the heterogeneous lesions in three-dimensional volume, providing an indispensable imaging tool for disease diagnosis, treatment planning, and surveillance in clinic. In oncological applications, solid tumors, regions of necrosis, and surrounding abnormality lesions are readily identified on MRI. However, the standing challenge of standard-of-care MRI is the lack of capability of decisively differentiating tissue pathologies prior to the manifestation of disease in the bulk volume.



Time-dependent diffusion MRI techniques have been developed to provide image contrast sensitive and specific to tissue structures at the microscopic level (~10^-3 mm), that is 100-1000 times below image voxel sizes (~1 mm). The root-mean-square displacement of water molecules during diffusion in a given time period (i.e., diffusion time) encodes their interactions with cellular structural barriers. Therefore, the functional dependence of diffusion coefficient on the diffusion time (i.e., time-dependent diffusion) reflects the size of the restricted cellular space. Short diffusion time, which is necessary to probe a short tissue length scale, has recently been achieved in high-performance gradient MRI system. Preliminary studies in cancer patients (1) have shown great promise for revealing heterogeneous tumor microstructures and differentiating tissue pathologies.



This talk will discuss: 1) how tissue microstructures at the length scale of micrometer can be specifically characterized by time-dependent diffusion MRI; 2) how the time-dependent diffusion MRI became feasibility in today’s MRI system; and 3) how MRI-based tissue microstructure imaging is defining the future of precision medicine.