Abstract
BackgroundIncreased brain uptake on [18F]AV45 PET is a biomarker for Alzheimer’s disease (AD). The standardised uptake value ratio (SUVR) is widely used for quantification but is subject to variability. Here we evaluate how SUVR of a cortical target region is affected by blood flow changes in the target and two frequently used reference regions.MethodsRegional baseline time-activity curves (TACs) were simulated based on metabolite-corrected plasma input functions and pharmacokinetic parameters obtained from our previously acquired data in healthy control (HC; n = 10), amnestic mild cognitive impairment (aMCI; n = 15) and AD cohorts (n = 9). Blood flow changes were simulated by altering the regional tracer delivery rate K1 (and clearance rate k2) between -40% and +40% from its regional baseline value in the target region and/or cerebellar grey (CB) or subcortical white matter (WM) reference regions. The corresponding change in SUVR was calculated at 50–60 min post-injection.ResultsA -40% blood flow reduction in the target resulted in an increased SUVRtarget (e.g. SUVRprecuneus: +10.0±5% in HC, +2.5±2% in AD), irrespective of the used reference region. A -40% blood flow reduction in the WM reference region increased SUVRWM (+11.5±4% in HC, +13.5±3% in AD) while a blood flow reduction in CB decreased SUVRCB (-9.5±6% in HC, -5.5±2% in AD), irrespective of the used target region. A -40% flow reduction in both the precuneus and reference WM (i.e., global flow change) induced an increased SUVR (+22.5±8% in HC, +16.0±4% in AD). When considering reference CB instead, SUVR was decreased by less than -5% (both in HC and AD).ConclusionBlood flow changes introduce alterations in [18F]AV45 PET SUVR. Flow reductions in the CB and WM reference regions resulted in a decreased and increased SUVR of the target, respectively. SUVR was more affected by global blood flow changes when considering WM instead of CB normalization.
Highlights
Alzheimer’s disease (AD), the most common cause of dementia, is associated with excessive accumulation of amyloid-β (Aβ) peptides and hyperphosphorylated tau in the brain [1]
A -40% blood flow reduction in the target resulted in an increased SUVRtarget (e.g. SUVRprecuneus: +10.0±5% in healthy control (HC), +2.5±2% in AD), irrespective of the used reference region
standardised uptake value ratio (SUVR) was more affected by global blood flow changes when considering white matter (WM) instead of cerebellar grey matter (CB) normalization
Summary
Alzheimer’s disease (AD), the most common cause of dementia, is associated with excessive accumulation of amyloid-β (Aβ) peptides and hyperphosphorylated tau in the brain [1]. The most widely used quantification index in amyloid PET is the standardised uptake value ratio (SUVR), which is the ratio of radioactivity concentration of the target and reference regions. This method is preferred for clinical use because of short scan duration and computational simplicity, but is subject to variability. The cerebellar grey matter (CB) has been the preferred reference region in clinical settings as it is notably free from fibrillar Aβ in sporadic AD This region might be susceptible to perfusion deficits, decreased glucose metabolism, and Aβ deposition in late-stage dementia or early-onset familial AD [5,11,12,13,14,15]. To date, the influence of perfusion changes in the frequently chosen reference regions (CB, WM) on amyloid quantification by SUVR remains elusive
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