Examining Tissue Microstructure with Temporal Diffusion Magnetic Resonance Spectroscopy

Abstract

Diffusion-weighted magnetic resonance imaging (DW-MRI) is a noninvasive imaging technique that can be used to quantify the rate of self-diffusion of water molecules. In biological tissues the mobility of water molecules is hindered by nuclear and cellular membranes, as well as by the presence of intracellular organelles, so the apparent rate of diffusion, described by the apparent diffusion coefficient (ADC), is reduced from that in a simple solution. Measurements of ADC reflect the density and scale of restrictive structures within the local cellular environment and may be used to characterize variations in tissue structure, such as those that accompany pathologies such as stroke or cancer. However, the majority of DW-MRI experiments continue to examine these processes over relatively long diffusion times (tens of milliseconds), such that variations in ADC reflect changes in tissue structure over a broad range of spatial scales, and obscure information about variations that arise on an intracellular scale. We have therefore implemented a novel imaging technique, known as temporal diffusion spectroscopy, in order to probe ADC over time scales as much as two orders of magnitude shorter than those previously reported. These methods, which involve rapid oscillations of the motion-sensitizing gradient fields, have been used to investigate variations in ADC in several biological systems, including cultured human embryonic kidney cells treated with various drugs that alter intracellular structure, as well as in an intracranial model of cancer in rats in vivo prior to and following chemotherapy. The reported results demonstrate the utility of these techniques for revealing details of tissue microstructure obscured by conventional methods, as well as for detecting the response of tumor cells to therapeutic treatment earlier than other methods.