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Clinical Evaluation of a New Concept: Resting Myocardial Perfusion Heterogeneity Quantified by Markovian Analysis of PET Identifies Coronary Microvascular Dysfunction and Early Atherosclerosis in 1,034 Subjects

¹ Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois
² Division of Cardiology, Department of Medicine, The Weatherhead PET Center for Preventing and Reversing Atherosclerosis, University of Texas Medical School at Houston and the Memorial Hermann Hospital, Houston, Texas

View larger version (29K): [in a new window]   FIGURE 1. Schematic demonstrates 4 topographic views of myocardial perfusion by PET. From left to right, views are left lateral, inferior, right or septal, and anterior. Each view corresponds to the distribution of coronary arteries shown.

View larger version (65K): [in a new window]   FIGURE 2. PET at rest and after dipyridamole stress in 3 clinical examples. As indicated by the color bar, white indicates maximal relative perfusion; red, high perfusion; yellow, intermediate; green and blue, progressively lower perfusion in continuous graded steps. (A) Young healthy normal volunteer without risk factors for vascular disease. (B) Severe stress-induced perfusion defect. (C) Abnormal base-to-apex longitudinal perfusion gradient with only a mild stress-induced regional perfusion defect.

View larger version (63K): [in a new window]   FIGURE 3. Display of relative activity distribution for Markovian homogeneity analysis, where each square panel corresponds to quadrants of the same 3 people illustrated in Figures 1 and 2. Quadrant squares indicate the area of heterogeneity analysis with the basal 4 slices and apex excluded from analysis as described. For the first rest–stress pair of the healthy control person (A), resting homogeneity index is 0.80 at rest and 0.83 after dipyridamole, both within normal limits of 50 healthy control subjects. For the second rest–stress pair of the person with a severe stress-induced perfusion defect (B), the homogeneity index is 0.34 at rest that is < 2 SD of healthy reference subjects and improves to 0.49 after dipyridamole, within 1 SD of healthy reference subjects, despite a severe stress-induced perfusion defect. For the third rest–stress pair of the person with a minimal perfusion abnormality (C), the homogeneity index is 0.26 at rest and improves to 0.40 after dipyridamole with an abnormal base-to-apex longitudinal perfusion gradient but no severe regional stress-induced perfusion defect.

View larger version (25K): [in a new window]   FIGURE 4. Graphs of base-to-apex longitudinal perfusion gradient expressed as first derivative or spatial slope of relative activity (vertical axis) at each tomographic slice from base-to-apex (horizontal axis) at rest (blue diamonds) and with dipyridamole stress (red Xs) with +2 SD and –2 SD limits of 50 reference subjects at rest (blue dashes) and after diypridamole (red dashes) for the same 3 clinical examples illustrated in Figures 2 and 3. Slope units are changes in relative activity per slice from base to apex. For the healthy control person (A), the base-to-apex longitudinal perfusion gradient at rest and during dipyridamole stress and the rest-to-stress change are both within 2 SD of 50 healthy control subjects. For the person with the severe stress-induced perfusion defect (B), the longitudinal perfusion gradient at rest and stress and the rest-to-stress change are all outside 2 SD of healthy reference subjects. For the person with the minimal perfusion abnormality (C), the longitudinal perfusion gradient and its rest-to-stress change are outside 2 SD limits of healthy reference subjects even though there is no clinically significant localized regional stress-induced perfusion defect.

View larger version (22K): [in a new window]   FIGURE 5. Bar graph of relative percentage distribution of subjects in 2 relative distribution of Table 3. Homogeneity was defined as abnormal if the resting homogeneity index and its rest-to-stress change were < 2 SD of healthy reference subjects, normal if both were > 2 SD, and borderline for all other unequal combinations of rest and rest-to-stress change as 1–2 SD, < 2 SD, and > 2 SD.