<sup>11</sup>
            C-PIB binding is increased in patients with cerebral amyloid angiopathy–related hemorrhage

Ly, John; Donnan, Geoffrey A.; Villemagne, Victor L.; Zavala, Jorge A.; Ma, Henry; O’Keefe, Graeme; Gong, Sylvia; Gunawan, Rico; Saunder, Timothy; Ackerman, Uwe; Tochon-Danguy, Henri; Чурилов, Леонид; Phan, Thanh G.; Rowe, Christopher C.

doi:10.1212/wnl.0b013e3181cef7e3

Cited by 145 publications

(169 citation statements)

References 39 publications

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“…This interpretation is consistent with extensive previous reports of associations between PiB retention and the hemorrhagic and ischemic markers of CAA. [7][8][9][10][11][12][13][14]36 The observation of increased relative florbetapir retention in occipital cortex (even after adjustment for global SUVR) further supports this interpretation, as this pattern parallels the posterior predominance of CAA pathology. 9,10,37 Some of the observed florbetapir retention likely also reflects accompanying parenchymal AD pathology, which often co-occurs with CAA (despite our restriction to cognitively normal patients with MMSE 29-30).…”

Section: Resultsmentioning

confidence: 79%

“…6 One of the exciting advances in CAA research has been the demonstration of the ability of Pittsburgh compound B (PiB), originally designed to detect plaque amyloid in Alzheimer disease (AD), to label vascular amyloid as well. [7][8][9][10] This PET tracer was shown to bind vascular amyloid by radiologic-pathologic correlation in both the common sporadic form of CAA and Iowa-type hereditary CAA, a form of the disorder with little or no plaque deposits of fibrillar Ab. 11,12 Amyloid imaging using PiB-PET has already made important contributions to our understanding of CAA-related hemorrhagic and ischemic disease mechanisms, 2,7,8,13,14 such as prediction of future hemorrhages.…”

Section: Classification Of Evidencementioning

confidence: 99%

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Florbetapir-PET to diagnose cerebral amyloid angiopathy

et al. 2016

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Objective: We hypothesized that florbetapir, a Food and Drug Administration-approved PET tracer, could distinguish cerebral amyloid angiopathy (CAA)-related intracerebral hemorrhage (ICH) from hypertensive ICH (HTN-ICH). Methods:We prospectively enrolled survivors of primary ICH related to probable CAA (per Boston Criteria, n 5 10) and HTN-ICH (n 5 9) without dementia. All patients underwent florbetapir-PET and multimodal MRI, and patients with CAA had additional Pittsburgh compound B (PiB) PET. Amyloid burden was assessed quantitatively (standard uptake value ratio [SUVR]) and visually classified as positive or negative. Results:The CAA and HTN-ICH groups had similar age (66.9 vs 67.1), sex, and leukoaraiosis volumes (31 vs 30 mL, all p . 0.8). Florbetapir uptake and PiB retention strongly correlated in patients with CAA both globally within cerebral cortex (r 5 0.96, p , 0.001) and regionally in lobar cortices (all r . 0.8, all p # 0.01). Mean global cortical florbetapir uptake was substantially higher in CAA than HTN-ICH (SUVR: 1.41 6 0.17 vs 1.15 6 0.08, p 5 0.001), as was mean occipital SUVR (1.44 6 0.12 vs 1.17 6 0.08, p , 0.001), even after correcting for global SUVR (p 5 0.03). Visual rating for positive/negative florbetapir demonstrated perfect interrater agreement (k 5 1) and was positive for all 10 patients with CAA vs 1 of 9 HTN-ICH patients (sensitivity 100%, specificity 89%).Conclusions: Florbetapir appears to label vascular amyloid in patients with CAA-related ICH. The approved florbetapir binary visual reading method can have diagnostic value in appropriate clinical settings. Classification of evidence:This study provides Class II evidence that florbetapir-PET provides a sensitivity of 100% (95% confidence interval [CI] 66%-100%) and specificity of 89% (95% CI 51%-99%) for determination of probable CAA among cognitively normal patients. Cerebral amyloid angiopathy (CAA), characterized by accumulation of b-amyloid (Ab) proteins in the walls of cortical/leptomeningeal vessels, is a common cause of vessel wall breakdown and vascular dysfunction in older adults, making it a major contributor to fatal or disabling intracerebral hemorrhages (ICH) as well as ischemic injury and dementia. 1,2 There currently is no specific treatment for CAA, in part because of our inability to identify this condition at early phases prior to appearance of multiple hemorrhagic brain lesions. 3 Accurate early diagnosis of CAA also has direct implications for stroke prevention, as this pathology is an important cause of anticoagulant-associated ICH and might dictate use of alternative nonpharmaceutical approaches such as left atrial appendage closure for patients with nonvalvular atrial fibrillation. 4,5

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Section: Resultsmentioning

confidence: 79%

Section: Classification Of Evidencementioning

confidence: 99%

Florbetapir-PET to diagnose cerebral amyloid angiopathy

et al. 2016

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“…11 C-PiB is also elevated in subjects diagnosed with cerebral amyloid angiopathy (66,67), showing a distribution similar to that in AD patients except that slightly greater binding may be seen in the occipital cortex.…”

Section: C-pib In Other Conditionsmentioning

confidence: 69%

Brain Amyloid Imaging

2011

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Imaging of brain b-amyloid plaques with 18 F-labeled tracers for PET will likely be available in clinical practice to assist the diagnosis of Alzheimer disease (AD). With the rapidly growing prevalence of AD as the population ages, and the increasing emphasis on early diagnosis and treatment, brain amyloid imaging is set to become a widely performed investigation. All physicians reading PET scans will need to know the complex relationship between amyloid and cognitive decline, how to best acquire and display images for detection of amyloid, and how to recognize the patterns of tracer binding in AD and other causes of dementia. This article will provide nuclear medicine physicians with the background knowledge required for understanding this emerging investigation, including its appropriate use, and prepare them for practical training in scan interpretation.

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“…As already pointed out, previous similar studies did not have such homogeneous CAA samples, which may explain their reported significant difference in wcDVR between patients and HAMCs. 6,10,12 In addition, in the Ly et al 10 study, 2/12 patients did not have T2* scans, and whether PiB þ HCs were excluded or not remains unclear. All our patients were on at least one, and several on up to four oral medications ( Table 1).…”

Section: Discussionmentioning

confidence: 99%

“…However, the quantitative analysis may perform better, given previous reports that suggest significantly higher occipital/frontal ratio in CAA as compared with AD. 6,10 We tested this hypothesis in a post hoc analysis using a sample of seven probable AD patients 39 (mean age: 66, range 59 to 73) from our center's database, which recovered the expected difference in calcarine/frontal DVR (0.94 ± 0.10 vs. 0.86 ± 0.07 in CAA and AD groups, respectively; one-tailed P ¼ 0.027). Although preliminary, these findings support the idea that amyloid imaging may be of use in diagnosing suspected CAArelated ICH according to the above two-step procedure according to a quantitative analysis.…”

Section: Discussionmentioning

confidence: 99%

Diagnostic Utility of Amyloid PET in Cerebral Amyloid Angiopathy-Related Symptomatic Intracerebral Hemorrhage

Baron

Farid

Dolan

et al. 2014

J Cereb Blood Flow Metab

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By detecting β-amyloid ( Aβ) in the wall of cortical arterioles, amyloid positron emission tomography (PET) imaging might help diagnose cerebral amyloid angiopathy (CAA) in patients with lobar intracerebral hemorrhage (I-ICH). No previous study has directly assessed the diagnostic value of 11-Pittsburgh compound B (PiB) PET in probable CAA-related I-ICH against healthy controls (HCs). 11C-PiB-PET and magnetic resonance imaging (MRI) including T2* were obtained in 11 nondemented patients fulfilling the Boston criteria for probable CAA-related symptomatic I-ICH (sl-ICH) and 20 HCs without cognitive complaints or impairment. After optimal spatial normalization, cerebral spinal fluid (CSF)-corrected PiB distribution volume ratios (DVRs) were obtained. There was no significant difference in whole cortex or regional DVRs between CAA patients and age-matched HCs. The whole cortex DVR was above the 95% confidence limit in 4/9 HCs and 10/11 CAA patients (sensitivity = 91%, specificity = 55%). Region/frontal or occipital ratios did not have better discriminative value. Similar but less accurate results were found using visual analysis. In patients with sl-ICH, 11C-PiB-PET has low specificity for CAA due to the frequent occurrence of high 11C-PiB uptake in the healthy elderly reflecting incipient Alzheimer's disease (AD), which might also be present in suspected CAA. However, a negative PiB scan rules out CAA with excellent sensitivity, which has clinical implications for prognostication and selection of candidates for drug trials.

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¹¹ C-PIB binding is increased in patients with cerebral amyloid angiopathy–related hemorrhage

Cited by 145 publications

References 39 publications

Florbetapir-PET to diagnose cerebral amyloid angiopathy

Florbetapir-PET to diagnose cerebral amyloid angiopathy

Brain Amyloid Imaging

Diagnostic Utility of Amyloid PET in Cerebral Amyloid Angiopathy-Related Symptomatic Intracerebral Hemorrhage

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11 C-PIB binding is increased in patients with cerebral amyloid angiopathy–related hemorrhage

Cited by 145 publications

References 39 publications

Florbetapir-PET to diagnose cerebral amyloid angiopathy

Florbetapir-PET to diagnose cerebral amyloid angiopathy

Brain Amyloid Imaging

Diagnostic Utility of Amyloid PET in Cerebral Amyloid Angiopathy-Related Symptomatic Intracerebral Hemorrhage

Contact Info

Product

Resources

About

¹¹ C-PIB binding is increased in patients with cerebral amyloid angiopathy–related hemorrhage