Heterogeneity of Apparent Diffusion Coefficients Within Infarcts
To the Editor:
Back et al1 recently reported apparent diffusion coefficient (ADC) measurements in acute stroke, finding no ADC fluctuations in peri-infarct regions over a 15-minute period. The reported data are convincing with regard to the temporal stability of infarct area within the 15-minute time window studied. We wish to address the issue of ADC spatial heterogeneity in stroke, specifically the authors’ contention that “there was a gradient of ADC reduction from the infarct periphery toward the infarct core.” They conclude that “this observation supports the view that the ischemia-induced early change in ADC is a blood flow-dependent event which reflects the severity (and duration) of the perfusion deficit.” As the authors have noted, this core-versus-periphery distinction in diffusion imaging has been previously advanced and is commonly accepted by the community of stroke researchers.
However, it is possible that much of the ADC heterogeneity illustrated in Figures 2 through 4 of the article by Back et al1 may reflect differences in ADC reduction between gray matter and white matter. Within the infarct, white matter structures appear to display lower ADC values than gray matter, a finding that is consistent with results from our investigation of acute and early subacute middle cerebral arterial stroke using diffusion tensor MR imaging.2 Indeed, the “peel-like structure” of the region of greatest ADC reduction (Figure 4) noted by Back et al1 closely resembles the morphology of white matter tracts. Our results from diffusion tensor imaging demonstrate that these areas of greatest ADC reduction within the infarct correspond also to the regions of highest diffusion anisotropy, a signature of white matter.
This difference in ADC reduction between gray and white matter is not likely to result from differences in severity of ischemia, as oxygen extraction fraction measured with positron emission tomography has not shown differences between ischemic gray and white matter.3 It is possible that, superimposed on these gray-white matter ADC differences, there may also be infarct ADC heterogeneity caused by varying degrees of ischemia, as suggested by Back et al.1 We feel that it is important to account for the variation in ADC due to these differences in gray matter–white matter anatomy before invoking heterogeneity of the ischemic process. Correlation of the ADC data with diffusion anisotropy can be helpful in this respect.
- Copyright © 2001 by American Heart Association
We thank Mukherjee and colleagues for their comments on our recent paper. Indeed, we agree on the intralesional heterogeneity and differential behavior of the ADC in gray and white matter, as observed by Mukherjee and others.R1 R2 Exactly as is described in their paper, in Figure 4 of our article a lower ADC in white matter than in gray matter is shown, and the description of a peel-like internal structure of ADC ranges when applying various ADC thresholds for analysis may appear misleading. Yet in regard to the main point of our paper, the stability of ADC values and the lack of any very short-term ADC change suggestive of peri-infarct depolarizations, white matter and gray matter ADCs were not different and in neither was any change of the ADC observed.
In regard to the differential behavior of gray and white matter ADC, one should consider the dynamic characteristics of the ADC over time as demonstrated in human and animal stroke.R3 R4 In a serial clinical study, we observed the earliest ADC reductions as early as 2 hours after symptom onset in gray matter (neuronal tissue may be more vulnerable to ischemia than white matter), followed by cortical swelling within 24 hours accompanied by a slow increase in the ADCs toward “pseudonormal” values. ADC reductions in the white matter occurred with a delay, but did not pseudonormalize as observed in gray matter. In this phase, as reported by Mukherjee et al (>16 hours after symptom onset) and as shown in our Figure 4, gray matter ADCs were reduced but higher than white matter ADCs. Yet exactly the opposite may be observed in the earliest phase of visible ADC changes in ischemic tissue, thus the time point after stroke is most important when differences between gray and white matter ADC values are discussed.
Mukherjee P, Bahn MM, McKinstry RC, Shimony JS, Cull TS, Akbudak E, Snyder AZ, Conturo TE. Differences between gray matter and white matter water diffusion in stroke: diffusion-tensor MR imaging in 12 patients. Radiology. 2000;215:211–220.
Nagesh V, Welch KM, 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;29:1778–1782.
Gass A, Behrens S, Hirsch JG, Sedlaczek O, Gaa J, Hennerici MG. Intralesional heterogeneity of the time course of the apparent diffusion coefficient in large territorial infarction. Stroke. 1999;30:260. Abstract.
Kuroiwa T, Nagaoka T, Ueki M, Yamada I, Miyasaka N, Akimoto H. Different apparent diffusion coefficient: water content correlations of gray and white matter during early ischemia. Stroke. 1998;29:859–865.