Abstract
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Objectives: The importance of small vessel disease (SVD), both in terms of its wide prevalence and as a source of cognitive impairment has not been fully appreciated. Previously, detection of SVD has been on the basis of structural changes on magnetic resonance imaging (MRI). We reasoned that SVD induces cerebral hypoperfusion before cerebral ischemic injury occurs. Since cerebral perfusion single photon emission computed tomography (SPECT), or CPS, directly measures that hypoperfusion, CPS should provide higher sensitivity than conventional imaging. Further, since SVD is a progressive age-related disease process, we reasoned that the CPS findings should show an age-relatedness.
Methods: 885 patients referred for memory impairment were evaluated with Tc-99m Bicisate CPS and brain MRI. Patients were classified by age (yrs): </=35, 36-55, and >/=56. A clinically relevant, ordinal rating scale was used: none=0, trace=1, mild=2, moderate=3, severe=4. This scale was used to quantify hypoperfusion on CPS in each of 5 white matter zones: periventricular, deep, corona radiata, centrum semi-ovale, and subcortical. Available MRIs for these patients were rated for white matter changes in a similar fashion. A total score was tabulated (from 0-20) for each MRI and CPS. Non-parametric ANOVA using the Kruskal-Wallis test was performed on both the scored data for all CPS (n=885) and MRI (n=368). Bonferroni correction of p<0.003 for the 5 white matter zones, and p<0.0167 for total scores. Regression analysis and Spearman correlation were performed on patients that had both CPS and MRI performed (n=348). [asterisk]This study was approved by the UB-IRB ID STUDY00000193.
Results: Kruskal-Wallis test with Bonferroni correction found a statistically significant difference among the age groups for each of the white matter zones for both CPS and MRI. There was also an age-wise increase in mean scores for all zones and for total scores, for both CPS and MRI. Regression analysis of patients who had both CPS and MRI scans showed a negative linear correlation, with R^2=0.266, as well as a negative polynomial correlation, with R^2=0.382, between CPS and MRI (Figure 1a). A modest linear relationship was also found between the severity of small vessel disease and age (Figure 1b).
Conclusion: Our results indicate the polynomial regression better estimates the relationship between CPS and MRI. This suggests that CPS is more sensitive than MRI at low SVD burden, and that at higher degrees of SVD burden, CPS’ selective sensitivity is diminished relative to MRI. A possible explanation for this is that in advanced SVD, there is structural changes including ischemic and reactive gliosis. Since the bicisate CPS signal requires brain cell uptake of tracer, the gliosis may abrogate SVD-induced CPS signal loss. However, early in the disease course, CPS may be more sensitive due to its ability to detect functional changes of hypoperfusion, which precede the structural changes of gliosis. We also found a statistically significant difference amongst age groups for both CPS and MRI, with a linear relationship in the extent of disease with age. This may indicate that this is a progressive disease process which is age-related, such as due to atherosclerosis. Overall, our results demonstrate that CPS is a sensitive diagnostic tool for the detection of SVD. The relative insensitivity of conventional imaging raise the implication that SVD may be a more significant source of morbidity that is currently recognized. We are currently investigating the role of cerebrovascular risk factors on white matter zone hypoperfusion to further support CPS as a screening tool for SVD. Research Support: William E. Mabie, DDS, and Grace S. Mabie Fund.