Dataset Information

Scan-Time Corrections for 80-100-min Standardizetd Uptake Volume Ratios to Measure the 18F-AV-1451 Tracer for Tau Imaging.

ABSTRACT: The 18F-AV-1451 PET tracer binds to tau, an Alzheimer's disease biomarker. The standardized uptake value ratio (SUVR) 80-100 min window is widely used to quantify tau binding, although 18F-AV-1451 continues increasing relative to a reference region in regions with tau deposition. Left uncorrected, acquisition time inaccuracies can lead to errors from -4% to 6% in 20-min SUVR measurements in subjects with Alzheimer's disease. In 40 subjects with scans from 75-115 min following 18F-AV-1451 injection, we created 20-min reconstructions (4×5 min) of start-times ranging from 75-85 min, as proxies of offset scans and calculated the mean in regions of interest (ROIs). We developed a segmented least squares (SLS) method to obtain error-minimizing weighting coefficients for 18F-AV-1451 ROIs that best predict SUVR 80-100 from weighted means of SUVRs from offset start-times. We compared residual errors of our SLS method to those in: 1) uncorrected offset 20-min-SUVRs; 2) the mean of five-min frames within the 80-100 window; and 3) a least-squares interpolation method. We evaluated errors induced by start-time offset on SUVRs for each method. TheSLS, which corrected using least-squares coefficients of 5-min components, consistently reduced errors across all offset starttimes. Effect size analysis for simulated clinical longitudinal 18F-AV-1451 drug trials showed that uncorrected 20-min offset SUVRs would require up to 20% more participants to detect treatment effects compared with using SLS. Correction of SUVR scan-time errors by SLS minimizes errors compared with other correction methods and may be extended to other scanners and tracers.

SUBMITTER: He M

PROVIDER: S-EPMC6475617 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Scan-Time Corrections for 80-100-min Standardizetd Uptake Volume Ratios to Measure the 18F-AV-1451 Tracer for Tau Imaging.

He Mark M Baker Suzanne L SL Shah Vyoma D VD Lockhart Samuel N SN Jagust William J WJ

IEEE transactions on medical imaging 20180917 3

The 18F-AV-1451 PET tracer binds to tau, an Alzheimer's disease biomarker. The standardized uptake value ratio (SUVR) 80-100 min window is widely used to quantify tau binding, although 18F-AV-1451 continues increasing relative to a reference region in regions with tau deposition. Left uncorrected, acquisition time inaccuracies can lead to errors from -4% to 6% in 20-min SUVR measurements in subjects with Alzheimer's disease. In 40 subjects with scans from 75-115 min followi ...[more]

PMID: 30235119

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Project description:BackgroundThe tau positron emission tomography (PET) ligand 18F-flortaucipir binds to paired helical filaments of tau in aging and Alzheimer's disease (AD), but its utility in detecting tau aggregates in frontotemporal dementia (FTD) is uncertain.MethodsWe performed 18F-flortaucipir imaging in patients with the FTD syndromes (n = 45): nonfluent variant primary progressive aphasia (nfvPPA) (n = 11), corticobasal syndrome (CBS) (n = 10), behavioral variant frontotemporal dementia (bvFTD) (n = 10), semantic variant primary progressive aphasia (svPPA) (n = 2) and FTD associated pathogenic genetic mutations microtubule-associated protein tau (MAPT) (n = 6), chromosome 9 open reading frame 72 (C9ORF72) (n = 5), and progranulin (GRN) (n = 1). All patients underwent MRI and β-amyloid biomarker testing via 11C-PiB or cerebrospinal fluid. 18F-flortaucipir uptake in patients was compared to 53 β-amyloid negative normal controls using voxelwise and pre-specified region of interest approaches.ResultsOn qualitative assessment, patients with nfvPPA showed elevated 18F-flortacupir binding in the left greater than right inferior frontal gyrus. Patients with CBS showed elevated binding in frontal white matter, with higher cortical gray matter uptake in a subset of β-amyloid-positive patients. Five of ten patients with sporadic bvFTD demonstrated increased frontotemporal binding. MAPT mutation carriers had elevated 18F-flortaucipir retention primarily, but not exclusively, in mutations with Alzheimer's-like neurofibrillary tangles. However, tracer retention was also seen in patients with svPPA, and the mutations C9ORF72, GRN predicted to have TDP-43 pathology. Quantitative region-of-interest differences between patients and controls were seen only in inferior frontal gyrus in nfvPPA and left insula and bilateral temporal poles in MAPT carriers. No significant regional differences were found in CBS or sporadic bvFTD. Two patients underwent postmortem neuropathological examination. A patient with C9ORF72, TDP-43-type B pathology, and incidental co-pathology of scattered neurofibrillary tangles in the middle frontal, inferior temporal gyrus showed corresponding mild 18F-flortaucipir retention without additional uptake matching the widespread TDP-43 type B pathology. A patient with sporadic bvFTD demonstrated punctate inferior temporal and hippocampus tracer retention, corresponding to the area of severe argyrophilic grain disease pathology.Conclusions18F-flortaucipir in patients with FTD and predicted tauopathy or TDP-43 pathology demonstrated limited sensitivity and specificity. Further postmortem pathological confirmation and development of FTD tau-specific ligands are needed.

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Project description:Primary progressive apraxia of speech (PPAOS) is a term used to describe a neurodegenerative condition in which apraxia of speech (AOS; a planning and/or programming deficit) occurs in the absence of aphasia (a language deficit). PPAOS is strongly associated with 4-repeat tau pathology. Elevated flortaucipir ([18F]AV-1451; FTP) uptake has been observed cross-sectionally in patients with PPAOS and those with aphasia. Here, we evaluated longitudinal changes in previously-identified regions of uptake and their relationship with clinical presentation. Thirteen patients who were diagnosed with PPAOS (5 female) at presentation underwent FTP PET imaging at two visits (mean 1 year interval). Median age was 72, with a median of 4 years disease duration at initial testing. Beta-amyloid status was assessed with Pittsburgh Compound B (PiB), where a global PiB ratio>1.48 was deemed amyloid positive (n = 4). FTP uptake was assessed as cortical to cerebellar crus ratios (SUVr) in cortical regions of interest. A single hierarchical linear model (HLM) compared PPAOS patients to 52 cognitively unimpaired controls of similar age and sex. Annualized SUVr change was the outcome, predicted by region, clinical status, and age. Person-specific effects accounted for intra-patient correlations and contralateral regions were included as repeated measures. Changes in clinical measures were assessed using Wilcoxon signed-rank tests; statistically significant changes in the Montreal Cognitive Assessment, MDS-UPDRS, motor section, and PSP Rating Scale were noted between visits. Changes in FTP SUVr were greater for patients than controls. The strongest changes in PPAOS patients were in the precentral gyrus, pallidum, and mid and superior frontal gyri, per the HLM. Qualitatively, larger changes were seen in patients who had developed aphasia by the time of their baseline scan (n = 5). While the biological mechanisms of FTP signal in non-AD tauopathies are unknown, this study demonstrates the utility of FTP in tracking disease progression in 4R tauopathies.

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Dataset Information

Scan-Time Corrections for 80-100-min Standardizetd Uptake Volume Ratios to Measure the 18F-AV-1451 Tracer for Tau Imaging.

Publications

Scan-Time Corrections for 80-100-min Standardizetd Uptake Volume Ratios to Measure the <sup>18</sup>F-AV-1451 Tracer for Tau Imaging.

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