Regional cortical perfusion on arterial spin labeling MRI in dementia with Lewy bodies: Associations with clinical severity, glucose metabolism and tau PET

Abstract

Visually preserved metabolism in posterior cingulate cortex relative to hypometabolism in precuneus and cuneus, the cingulate island sign, is a feature of dementia with Lewy bodies (DLB) on FDG-PET. Lower cingulate island sign ratio (posterior cingulate cortex/cuneus+precuneus; FDG-CISr) values have been associated with a higher Braak neurofibrillary tangle stage in autopsied DLB. Using voxel-wise analysis, we assessed the patterns of regional cortical perfusion and metabolism, and using an atlas-based approach, we measured perfusion cingulate island sign ratio on arterial spin labeling MRI (ASL-CISr), and its associations with FDG-CISr, uptake on tau-PET and clinical severity in DLB. Our study sample (n = 114) included clinically probable DLB patients (n = 19), age-matched patients with probable Alzheimer's disease dementia (AD; n = 19) and matched controls (n = 76) who underwent MRI with 3-dimensional pseudo-continuous arterial spin labeling, 18F-FDG-PET and 18F-AV-1451 tau PET. Patterns of cortical perfusion and metabolism were derived from quantitative maps using Statistical Parametric Mapping. DLB patients showed hypoperfusion on ASL-MRI in precuneus, cuneus and posterior parieto-occipital cortices, compared to controls, and relatively spared posterior cingulate gyrus, similar to pattern of hypometabolism on FDG-PET. DLB patients had higher ASL-CISr and FDG-CISr than AD patients (p <0.001). ASL-CISr correlated with FDG-CISr in DLB patients (r = 0.67; p =0.002). Accuracy of distinguishing DLB from AD patients was 0.80 for ASL-CISr and 0.91 for FDG-CISr. Lower ASL-CISr was moderately associated with a higher composite medial temporal AV-1451 uptake (r = -0.50; p =0.03) in DLB. Lower perfusion in precuneus and cuneus was associated with worse global clinical scores. In summary, the pattern of cortical hypoperfusion on ASL-MRI is similar to hypometabolism on FDG-PET, and respective cingulate island sign ratios correlate with each other in DLB. Non-invasive and radiotracer-free ASL-MRI may be further developed as a tool for the screening and diagnostic evaluation of DLB patients in a variety of clinical settings where FDG-PET is not accessible.

Keywords: Arterial spin labeling MRI; Cingulate island sign ratio; Cortical perfusion; Dementia with Lewy bodies; FDG PET; Or AV1–1451 tau PET.

Graphical abstract

Fig. 1

Cortical hypoperfusion on ASL-MRI and hypometabolism on FDG-PET in DLB patients. Regional cortical hypoperfusion on ASL is compared voxel-wise between DLB patients and CN (top panels). Pattern of cortical hypometabolism on FDG-PET is shown in the bottom panels. In the uncorrected analysis (p <0.001, top left), DLB patients have hypoperfusion in the medial parieto-occipital cortices, specifically in precuneus and cuneus and in the lateral occipital and temporo-parietal cortex (e.g. angular, supramarginal and middle and inferior temporal gyrus) compared to CN. The perfusion in posterior cingulate gyrus is relatively spared. Pattern of hypoperfusion is similar to hypometabolism (bottom left), although the hypometabolism is more wide-spread involving voxels in temporo-parietal and frontal cortices. The posterior cingulate gyrus is only marginally involved. After voxel-wise correction for multiple comparisons with family-wise error (FWE) (p <0.05, top right), the hypoperfusion remains confined to precuneus and cuneus and also supramarginal and angular gyrus. Hypometabolic areas overlap with hypoperfusion, although hypometabolism extends more into lateral temporo-parietal and to a lesser degree into frontal cortices (bottom right).

Fig. 2

Differences in ASL-CISr and FDG-CISr by clinical group. Box-and-whisker plots show differences in magnitude of ASL-CISr and FDG-CISr; DLB patients have the highest CIS ratios whereas AD dementia patients have the lowest CIS ratios.

Fig. 3

Correlation between ASL-CISr and FDG-CISr. Scatter plot shows Pearson correlation between FDG-CISr and ASL-CISr in DLB patients (red dots; r_p = 0.67; p =0.002) and among all (r_p = 0.52; p <0.001).

Fig. 4

Correlation between perfusion cingulate island sign ratio and medial temporal tau AV-1451 uptake in DLB. Pearson correlation between a higher composite medial temporal AV-1451 uptake as a proxy of AD-related tau pathology and lower ASL-CISr in DLB patients (r = −0.50; p =0.03). The SUVr of AV-1451 uptake is log-transformed.

Fig. 5

Individual imaging findings in DLB and AD patients. Left: a 70 years old male DLB patient who has visually preserved CIS on ASL and FDG-PET: the arrow head points to the relatively preserved perfusion in the posterior cingulate cortex, when compared to a lower signal in precuneus and cuneus. He has a minimal medial temporal AV-1451 uptake (the bright spot on the right side is a non-specific uptake in the choroid plexus and not in the hippocampus itself). Middle: A 74 years old male AD dementia patient who does not have visually preserved CIS on ASL or FDG-PET. He has a considerable AV-1451 uptake including the medial temporal cortex. Right: an 82 years old male DLB patient who does not have visually preserved CIS on either ASL or FDG-PET and he has higher medial temporal AV-1451 uptake than DLB patient to the left.

Fig. 6

Discrimination between DLB and AD patients using CISr. The receiver operating characteristics (ROC) curves are shown for ASL-CISr and for FDG-CISr for distinguishing DLB and AD dementia patients. The overall accuracy for ASL-CISr corresponds to area under the ROC (AUROC) of 0.80 (95% CI 0.79–1.00) and for FDG-CISr to AUROC of 0.91 (95% CI 0.65–0.95). Various sensitivities and associated specificities for both measures are listed.