Reduction of Diffusion-Weighted Imaging Contrast of Acute Ischemic Stroke at Short Diffusion Times

Abstract

Background and Purpose— Diffusion-weighted imaging (DWI) of tissue water is a sensitive and specific indicator of acute brain ischemia, where reductions of the diffusion of tissue water are observed acutely in the stroke lesion core. Although these diffusion changes have been long attributed to cell swelling, the precise nature of the biophysical mechanisms remains uncertain. Methods— The potential cause of diffusion reductions after stroke was investigated using an advanced DWI technique, oscillating gradient spin-echo DWI, that enables much shorter diffusion times and can improve specificity for alterations of structure at the micron level. Results— Diffusion measurements in the white matter lesions of patients with acute ischemic stroke were reduced by only 8% using oscillating gradient spin-echo DWI, in contrast to a 37% decrease using standard DWI. Neurite beading has recently been proposed as a mechanism for the diffusion changes after ischemic stroke with some ex vivo evidence. To explore whether beading could cause such differential results, simulations of beaded cylinders and axonal swelling were performed, yielding good agreement with experiment. Conclusions— Short diffusion times result in dramatically reduced diffusion contrast of human stroke. Simulations implicate a combination of neuronal beading and axonal swelling as the key structural changes leading to the reduced apparent diffusion coefficient after stroke.

Design and Validation of Diffusion MRI Models of White Matter

“…Compartment-specific tracer studies have indicated that the intracellular and extracellular compartments exhibit similar decreases in diffusion (Duong et al, 1998; Silva et al, 2002), while others have shown that intracellular diffusivity decreases substantially while the extracellular diffusivity experiences a somewhat lesser decrease (Goodman et al, 2008). The extracellular decrease is consistent with a reduction in the extracellular space and increase in tortuosity that leads to decreased diffusivity in that compartment (Latour et al, 1994), while the intracellular decrease is consistent with neurite beading (Baron et al, 2015; Budde and Frank, 2010). Oscillating gradient measurements in the rat brain have demonstrated that restrictions caused by ischemia occur on the scale of several microns typical of cell sizes (Does et al, 2003).…”

Fundamentals of diffusion MRI physics

“…This allows a deeper understanding of certain phenomena that have been known for years. Two illustrative examples are the interpretation of results of Does et al given a decade later, suggesting a one‐dimensional nature of diffusion in the brain, and the measurement of the frequency‐dependent diffusion tensor, which revealed a pronounced anisotropy of diffusion reduction in ischemia …”

“…A famous achievement of this kind is the discovery of the almost twofold reduction in diffusion coefficient in irreversibly damaged brain tissues . The mechanism of this effect is still disputed, with some hope for understanding having been recently expressed …”

Quantifying brain microstructure with diffusion MRI: Theory and parameter estimation

“…The parameter D a takes into account all restrictions, such as varicosities (beads) and undulations, along the (average) neurite direction. Hence, it can have important biophysical and diagnostic value in cases when the structure along neurites changes, eg, in acute stroke() and Alzheimer's disease Exchange between intra‐ and extra‐neurite water can be neglected, at least at the time scales t used in clinical dMRI.…”