Microangiopathy underlying mixed-location intracerebral hemorrhages/microbleeds: A PiB-PET study

Abstract

Objective: To test the hypothesis that patients with concomitant lobar and deep intracerebral hemorrhages/microbleeds (mixed ICH) have predominantly hypertensive small vessel disease (HTN-SVD) rather than cerebral amyloid angiopathy (CAA), using in vivo amyloid imaging.

Methods: Eighty Asian patients with primary ICH without dementia were included in this cross-sectional study. All patients underwent brain MRI and ¹¹C-Pittsburgh compound B (PiB)-PET imaging. The mean cortical standardized uptake value ratio (SUVR) was calculated using cerebellum as reference. Forty-six patients (57.5%) had mixed ICH. Their demographic and clinical profile as well as amyloid deposition patterns were compared to those of 13 patients with CAA-ICH and 21 patients with strictly deep microbleeds and ICH (HTN-ICH).

Results: Patients with mixed ICH were younger (62.8 ± 11.7 vs 73.3 ± 11.9 years in CAA, p = 0.006) and showed a higher rate of hypertension than patients with CAA-ICH (p < 0.001). Patients with mixed ICH had lower PiB SUVR than patients with CAA (1.06 [1.01-1.13] vs 1.43 [1.06-1.58], p = 0.003). In a multivariable logistic regression model, mixed ICH was associated with hypertension (odds ratio 8.9, 95% confidence interval 1.4-58.4, p = 0.02) and lower PiB SUVR (odds ratio 0.03, 95% confidence interval 0.001-0.87, p = 0.04) compared to CAA after adjustment for age. Compared to HTN-ICH, mixed ICH showed a similar mean age (62.8 ± 11.7 vs 60.1 ± 14.5 years in HTN-ICH) and risk factor profile (all p > 0.1). Furthermore, PiB SUVR did not differ between mixed ICH (values presented above) and HTN-ICH (1.10 [1.00-1.16], p = 0.45).

Conclusions: Patients with mixed ICH have much lower amyloid load than patients with CAA-ICH, while being similar to HTN-ICH. Overall, mixed ICH is probably caused by HTN-SVD, an important finding with clinical relevance.

Figure 1. Flowchart of patient enrollment and final study sample

CAA = cerebral amyloid angiopathy; CMB = cerebral microbleed; HTN = hypertension; ICH = intracerebral hemorrhage.

Figure 2. Imaging features of mixed ICH

(A) Patient with deep ICH (thick arrow) and lobar CMB (arrowhead). Some deep CMBs are also seen (thin arrows). (B) Patient with lobar ICH (thick arrow) and deep CMB (arrowhead). (C) Patient with deep (thick arrows) and lobar ICHs (thin arrow). CMB = cerebral microbleed; ICH = intracerebral hemorrhage.

Figure 3. The global amyloid retention in different ICH categories

Boxplot showing the median values and interquartile ranges of the SUVR in CAA-related ICH (CAA-ICH); hypertensive ICH (HTN-ICH); and mixed-location ICH (mixed ICH). CAA = cerebral amyloid angiopathy; HTN = hypertension; ICH = intracerebral hemorrhage; SUVR = standardized uptake value ratio.

Figure 4. MRI and PiB scan sets representative of different ICH categories

(A) CAA-ICH with right occipital hemorrhage (thick arrow) and superficial siderosis (thin arrows). PiB-PET shows increased cortical amyloid retention (SUVR = 1.57). (B) HTN-ICH with right basal ganglia ICH (thick arrow). PiB-PET shows absent cortical amyloid retention (SUVR = 1.01). (C) Mixed ICH with ICHs in bilateral basal ganglia and right occipital lobe (thick arrows). PiB-PET shows absent cortical amyloid retention (SUVR = 1.06). (D) Mixed ICH with ICH in the right parieto-occipital region (thick arrow) and a microbleed in the right thalamus (arrowhead). Superficial siderosis is also seen (thin arrow). PiB-PET shows mildly increased cortical amyloid retention (SUVR = 1.22). CAA = cerebral amyloid angiopathy; HTN = hypertension; ICH = intracerebral hemorrhage; PiB = Pittsburgh compound B; SUVR = standardized uptake value ratio.