Topography of 11C-Pittsburgh compound B uptake in Alzheimer’s disease: a voxel-based investigation of cortical and white matter regions

Abstract

Objective:To compare results of positron emission tomography (PET) with carbon-11-labeled Pittsburgh compound B (11C-PIB) obtained with cerebellar or global brain uptake for voxel intensity normalization, describe the cortical sites with highest tracer uptake in subjects with mild Alzheimer’s disease (AD), and explore possible group differences in 11C-PIB binding to white matter.Methods: 11C-PIB PET scans were acquired from subjects with AD (n=17) and healthy elderly controls (n=19). Voxel-based analysis was performed with statistical parametric mapping (SPM).Results:Cerebellar normalization showed higher 11C-PIB uptake in the AD group relative to controls throughout the cerebral cortex, involving the lateral temporal, orbitofrontal, and superior parietal cortices. With global uptake normalization, greatest cortical binding was detected in the orbitofrontal cortex; decreased 11C-PIB uptake in white matter was found in the posterior hippocampal region, corpus callosum, pons, and internal capsule.Conclusion:The present case-control voxelwise 11C-PIB PET comparison highlighted the regional distribution of amyloid deposition in the cerebral cortex of mildly demented AD patients. Tracer uptake was highest in the orbitofrontal cortex. Decreased 11C-PIB uptake in white-matter regions in this patient population may be a marker of white-matter damage in AD.

Subjective sleep parameters in prodromal Alzheimer’s disease: a case-control study

“…Production of the [ 11 C]PiB-PET radiochemical has been described in detail elsewhere. 16 Two certified nuclear medicine physicians with more than 5 years of experience evaluated the [ 11 C]PiB-PET images, blinded to clinical diagnosis and to the other's interpretation. They independently rated the individual images as ''positive'' (A+) and ''negative'' (A-).…”

Hippocampal subregional volume changes in elders classified using positron emission tomography‐based Alzheimer's biomarkers of β‐amyloid deposition and neurodegeneration

“…Also, in order to verify whether significant findings in hippocampal subregions could reflect a global pattern of brain atrophy, we used measures of total GM in the brain, corrected for ICV. The protocol for [ 11 C]PIB radiochemical production has been described in detail elsewhere (Faria et al, 2019).…”

“…Therefore, the combination of clinical and biological markers supportive of AD is the mainstay of the “AD continuum,” ranging from asymptomatic/subsymptomatic forms (“preclinical AD”) to mildly symptomatic (“mild cognitive impairment due to AD” or “prodromal AD”) and fully symptomatic cases (“dementia due to AD”). Measurements for the A+ and T+ biomarker groups are obtained either by: cerebrospinal fluid (CSF) measurements of the 42‐residue Aβ isoform (Aβ 42 ) and phosphorylated tau (Blennow et al., 2010; Forlenza et al., 2015), or using positron emission tomography (PET) respectively with well‐established Aβ imaging radioligands (such as Pittsburgh compound B (PIB) labeled with carbon‐11; [ 11 C]PIB‐PET; Faria et al., 2019), and recently developed tau imaging tracers (Lowe et al., 2019). Imaging biomarkers of neurodegeneration include: brain volumetric reductions as assessed by magnetic resonance imaging (MRI; which reflect loss of neurons and neuropil shrinkage; Schuff et al., 2009); and PET with [ 18 F]fluorodeoxyglucose ([ 18 F]FDG‐PET) to measure brain glucose metabolism (a highly sensitive marker that reflects functional neuronal deficits and neuropil loss; Herholz et al., 2002; Mosconi et al., 2008).…”

Correlação de imagens metabólicas (PET 18F-FDG) com imagens de fluxo sanguíneo (PET 11C-PIB) em idosos com queixa de memória

“…Como já mencionado anteriormente, as imagens obtidas entre 40 a 70 minutos após injeção intravenosa de 11 C-PIB (Klunk et al, 2015(Klunk et al, , 2004 (Faria, et al, 2018; Cohen e Klunk, 2014), figura 6.…”

“…A) Concentração de 11 C-PIB na substância branca, sendo considerado um exame negativo. B) Presença da concentração de 11 C-PIB no córtex cerebral, sendo considerado um estudo positivo, adaptada de (Faria, et al, 2018).…”