Diagnostic Utility of Integrated11C-Pittsburgh Compound B Positron Emission Tomography/Magnetic Resonance for Cerebral Amyloid Angiopathy: A Pilot Study

Abstract

Objective: We aimed to compare amyloid deposition at the lobar cerebral microbleed (CMB) sites of cerebral amyloid angiopathy (CAA), Alzheimer’s disease (AD), and cognitively normal healthy controls (NC) and to propose a novel diagnostic method for differentiating CAA patients from AD patients with integrated 11C-Pittsburgh compound B (PIB) positron emission tomography (PET)/magnetic resonance (MR) and assess its diagnostic value.Methods: Nine CAA, 15 AD patients, and 15 NC subjects were enrolled in this study. Each subject underwent an 11C-PIB brain PET/MR examination. Susceptibility weighted imaging was assessed to detect CMB locations, and standardized uptake value ratios (SUVRs) were measured at these sites. Cortical PIB distributions were quantitatively evaluated. Patients with CAA, AD, and NC subjects were compared with global and regional cortical SUVRs at CMB cites. The diagnostic accuracy of MRI, PIB-PET, and PET/MR in differentiating CAA and AD was evaluated.Results: Lobar CMBs were detected in all the CAA patients, eight of the 15 AD patients (53.3%), and four of the 15 NC subjects (26.7%), respectively. The PIB deposition at CMB sites was significantly higher in CAA patients compared with AD patients and NC subjects in terms of SUVR (1.72 ± 0.10 vs. 1.42 ± 0.16 and 1.17 ± 0.08; p < 0.0001). The PIB deposition was associated with CMB locations and was greatest in the occipital and temporal regions of CAA patients. The global cortical PIB deposition was significantly higher in CAA than in NC subjects (1.66 ± 0.06 vs. 1.21 ± 0.06; p < 0.0001) and significantly lower than in AD patients (1.66 ± 0.06 vs. 1.86 ± 0.17; p < 0.0001). In contrast, the occipital/global PIB uptake ratio was significantly increased in CAA (occipital/global ratio, 1.05 ± 0.02) relative to AD patients (1.05 ± 0.02 vs. 0.99 ± 0.04; p < 0.001). PET/MR had a higher accuracy (sensitivity, 88.9%; specificity, 93.3%) than separate PET and MR.Conclusion: Our results indicate that the CMBs occur preferentially at loci with concentrated amyloid. By combining lobar CMBs with regional cortical amyloid deposition, the proposed workflow can further improve CAA diagnostic accuracy compared to each method alone. These findings improve our knowledge regarding the pathogenesis of CMBs and highlight the potential utility of PIB-PET/MR as a non-invasive tool for distinguishing CAA and AD patients.

PET imaging for the evaluation of cerebral amyloid angiopathy: a systematic review

“…Similarly, Dierksen et al [17] reported an elevated occipital-to-global ratio for CAA patients compared to AD patients. In this scenario Chang et al [41] reported lower global cortical 11 C-PIB uptake for CAA patients compared to AD, however, tracer uptake in occipital regions was higher in CAA compared to AD patients. In contrast, AD subjects had higher lateral temporal lobe deposition of tracer.…”

“…Similarly, Gurol et al [19] confirmed this correlation with new bleeds, reporting that increased tracer retention characterized sites of future bleeds and a higher risk of incidental bleeds. Again, Chang et al [41] reported higher SUV values in CMB area of patients with CAA compared with those of AD or healthy subjects. In this setting Ly et al [18] reported increased 11 C-PIB uptake in patients with CAA-related hemorrhage (CAAH) and higher binding of tracer in patients with probable CAAH compared to patients with possible CAAH.…”

“…Among the 29 studies included in the systematic review, 6 were of retrospective nature [22,28,29,34,39,40] while 23 had a prospective design [17-21, 23-27, 30-33, 35-38, 41-45]. Regarding the device used for scan acquisition, 8 studies used PET only [17][18][19][20][21][22][23][24], 17 studies used PET/CT [25-32, 34-37, 39, 40, 42-45] while 3 studies used PET/ MR [33,38,41]. Speaking about radiotracer, 11 C-PIB was used in 13 studies [17-22, 28, 31, 32, 37, 41, 42, 45], 5 studies used 18 F-florbetapir [25,30,33,35,36], 18 F-FDG was used in 3 studies [23,39,40], 18 F-florbetaben ( 18 F-FBB) was used in 2 studies [26,27] and 18 F-flutemetamol was used in one study [38].…”

“…The ability of 11 C-PIB PET imaging to differentiate between CAA and AD was investigated by some works [17,18,20,22,41] In general higher tracer retention was associated with the presence of CAA and occipital regions were characterized by higher uptake compared to AD.…”

Association of candidate genetic variants and circulating levels of ApoE/ApoJ with common neuroimaging features of cerebral amyloid angiopathy

“…Detecting the cerebrovascular Aβ pathology is a crucial endpoint with diagnostic value and potential for monitoring CAA progression. In recent years, the development of positron emission tomography (PET) radiotracers for Aβ imaging (Farid et al, 2017;Chang et al, 2021) and cerebrospinal fluid (CSF) biomarkers (Kuiperij et al, 2020) have been an intensive focus of research in Allelic distribution of the SNPs associated with the CAA-SVD burden score using the common dominant model. The genetic risk factor (presenting or not the minor allele) associated with a higher score is represented in dark gray, whereas the protective factor is represented in light gray.…”