Time Course of ADCW Changes in Ischemic Stroke
To the Editor:
Our laboratory team was excited to learn of the observation that there is an early increase in apparent diffusion coefficient (ADC) at the edge of ischemic lesions during stroke.1 We have recently completed a study that actually predicts this result and provides a potential explanation.2 Using 1000-μm-thick hippocampal brain slices as a model of the ischemic penumbra and a series of radiotracer molecules, we observed an increase in the rate of extracellular diffusion under ischemic conditions. Even though the extracellular space (ECS) was modestly reduced in volume in these slices, the diffusion coefficient rose with all 4 tracers. We have interpreted our surprising results as indicating that ECS becomes less tortuous during mild-to-moderate ischemia. In the simplest model, this would be explained by postulating that there are large and small fluid channels in the ECS of brain with different rates of diffusion, and that during less severe ischemia, the smaller and more slowly diffusing channels close while the larger, more rapidly diffusing channels remain open. The result is a net increase in the rate of diffusion even though ECS volume declines. Naturally, there are other interpretations. However, based on these results, we have predicted that there should be a measurable increase in the ADC of brain regions exposed to flow rates of 20 to 30 mL/100 g per minute.
It is clear that ischemic injury is a complex and dynamic process. The meticulous measurements involved in this MRI study provide a valuable example of how that complexity can be unraveled when there is sufficient attention to detail. The more finely we analyze our clinical and imaging observations, the more likely we are to find useful correlations with measurements made in model systems.
- Copyright © 1999 by American Heart Association
We thank Dr Newman for his gracious comments on our paperR1 and for drawing our attention to the recent body of work by his team on the diffusion of radiotracers in ischemic brain slices.R2 Their interpretation of an increased ADC resulting from the ECS being less tortuous is provided by comprehensive diffusion-compartment analysis. We believe their work on tracer kinetic analyses in conjunction with histology in thick slices provides important and relevant information for the assessment of ischemic tissue in humans, particularly the penumbral region that is potentially salvageable.
The signal in diffusion-weighted MRI (DW-MRI) is a weighted average of intracellular and extracellular protons (with 75% to 80% of the protons being intracellular). The ADC value of each of the individual compartments cannot be resolved in our MRI studies. Nevertheless, the sensitivity of the quantitative diffusion coefficient to ischemia offers an opportunity to resolve the heterogeneity and temporal evolution of the injury. Based on experimental animal models, an MR tissue signature model using ADC and T2 measures was developed to predict the histopathology of human stroke.R3 Results of the study confirmed heterogeneity of tissue damage and differing rates of evolution toward infarction (in different patients). Yet again, stroke in humans is a highly individualized event, due to the complex interaction of numerous biophysical and biochemical processes.
Nagesh V, Welch KMA, Windham JP, Patel S, Levine SR, Hearshen D, Peck D, Robbins K, D’Olhaberriague L, Soltanian-Zadeh H, Boska MD. Time course of ADCW changes in ischemic stroke: beyond the human eye! Stroke. 1998;29:1778–1783.
Patlak CS, Hospod FE, Trowbridge SD, Newman GC. Diffusion of radiotracers in normal and ischemic brain slices. J Cereb Blood Flow Metab. 1998;18:778–802.
Welch KMA, Windham JP, Knight RA, Nagesh V, Hugg J, Jacobs M, Peck D, Booker P, Dereski MO, Levine SR. A model to predict the histopathology of human stroke using diffusion and T2-weighted magnetic resonance imaging. Stroke. 1995;26:1983–1989.