Test–retest repeatability of [18F]Flortaucipir PET in Alzheimer’s disease and cognitively normal individuals

The aim of this study was to investigate the test–retest (TRT) repeatability of various parametric quantification methods for [18F]Flortaucipir positron emission tomography (PET). We included eight subjects with dementia or mild cognitive impairment due to Alzheimer’s disease and six cognitively normal subjects. All underwent two 130-min dynamic [18F]Flortaucipir PET scans within 3 ± 1 weeks. Data were analyzed using reference region models receptor parametric mapping (RPM), simplified reference tissue method 2 (SRTM2) and reference logan (RLogan), as well as standardized uptake value ratios (SUVr, time intervals 40–60, 80–100 and 110–130 min post-injection) with cerebellar gray matter as reference region. We obtained distribution volume ratio or SUVr, first for all brain regions and then in three tau-specific regions-of-interest (ROIs). TRT repeatability (%) was defined as |retest–test|/(average (test + retest)) × 100. For all methods and across ROIs, TRT repeatability ranged from (median (IQR)) 0.84% (0.68–2.15) to 6.84% (2.99–11.50). TRT repeatability was good for all reference methods used, although semi-quantitative models (i.e. SUVr) performed marginally worse than quantitative models, for instance TRT repeatability of RPM: 1.98% (0.78–3.58) vs. SUVr80–100: 3.05% (1.28–5.52), p < 0.001. Furthermore, for SUVr80–100 and SUVr110–130, with higher average SUVr, more variation was observed. In conclusion, while TRT repeatability was good for all models used, quantitative methods performed slightly better than semi-quantitative methods.

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Evaluation of Imaging Windows for Tau PET Imaging Using 18F-PI2620 in Cognitively Normal Individuals, Mild Cognitive Impairment, and Alzheimer’s Disease Patients

Molecular Imaging ◽

10.1177/1536012120947582 ◽

2020 ◽

Vol 19 ◽

pp. 153601212094758 ◽

Cited By ~ 1

Author(s):

Chanisa Chotipanich ◽

Monchaya Nivorn ◽

Anchisa Kunawudhi ◽

Chetsadaporn Promteangtrong ◽

Natphimol Boonkawin ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Standardized Uptake Value ◽

Brain Regions ◽

Post Injection ◽

Cognitively Normal ◽

Scanning Time ◽

Normal Individuals

Background: The study aimed to evaluate the appropriate uptake-timing in cognitively normal individuals, mild cognitive impairment (MCI), and Alzheimer’s disease (AD) patients, using 18F-PI 2620 dynamic PET acquisition. Methods: Thirty-four MCI patients, 6 AD patients, and 24 cognitively normal individuals were enrolled in this study. A dynamic 18F-PI 2620 PET study was conducted at 30-75 minutes post-injection in these groups. Co-registration was applied between the dynamic acquisition PET and T1-weighted MRI to delineate various cortical regions. The standardized uptake value ratio (SUVR) was used for quantitative analysis. P-mod software with the Automated Anatomical Labeling (AAL)-merged atlas was employed to generate automatic volumes of interest for 11 brain regions. Results: The curves in most brain regions presented an average SUVR stability at 30-40 minutes post-injection in each group. The appropriate uptake-timing interval of 18F-PI 2620 was 30-75 minutes post injection for AD group and 30-40 minutes post injection for both cognitively normal individuals and MCI groups. Conclusion: Short uptake time around 30-40 minutes post-injection would be more comfortable and convenient for all patients, especially in those with dementia who were unable to stay motionless for long periods of scanning time in the scanner.

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Association between GAB2 haplotype and higher glucose metabolism in Alzheimer's disease-affected brain regions in cognitively normal APOEε4 carriers

NeuroImage ◽

10.1016/j.neuroimage.2010.09.066 ◽

2011 ◽

Vol 54 (3) ◽

pp. 1896-1902 ◽

Cited By ~ 14

Author(s):

Winnie S. Liang ◽

Kewei Chen ◽

Wendy Lee ◽

Kunal Sidhar ◽

Jason J. Corneveaux ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Glucose Metabolism ◽

Brain Regions ◽

Cognitively Normal

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Repeatability of parametric methods for [18F]florbetapir imaging in Alzheimer’s disease and healthy controls: A test–retest study

Journal of Cerebral Blood Flow & Metabolism ◽

10.1177/0271678x20915403 ◽

2020 ◽

pp. 0271678X2091540 ◽

Cited By ~ 1

Author(s):

Sander CJ Verfaillie ◽

Sandeep SV Golla ◽

Tessa Timmers ◽

Hayel Tuncel ◽

Chris WJ van der Weijden ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Standardized Uptake Value ◽

Emission Tomography ◽

Parametric Methods ◽

Excellent Performance ◽

Reference Tissue ◽

Positron Emission ◽

Arterial Sampling ◽

Pet Scans

Accumulation of amyloid beta (Aβ) is one of the pathological hallmarks of Alzheimer’s disease (AD), which can be visualized using [18F]florbetapir positron emission tomography (PET). The aim of this study was to evaluate various parametric methods and to assess their test-retest (TRT) reliability. Two 90 min dynamic [18F]florbetapir PET scans, including arterial sampling, were acquired ( n = 8 AD patient, n = 8 controls). The following parametric methods were used; (reference:cerebellum); Logan and spectral analysis (SA), receptor parametric mapping (RPM), simplified reference tissue model2 (SRTM2), reference Logan (rLogan) and standardized uptake value ratios (SUVr(50–70)). BPND+1, DVR, VT and SUVr were compared with corresponding estimates (VT or DVR) from the plasma input reversible two tissue compartmental (2T4k_VB) model with corresponding TRT values for 90-scan duration. RPM ( r2 = 0.92; slope = 0.91), Logan ( r2 = 0.95; slope = 0.84) and rLogan ( r2 = 0.94; slope = 0.88), and SRTM2 ( r2 = 0.91; slope = 0.83), SA ( r2 = 0.91; slope = 0.88), SUVr ( r2 = 0.84; slope = 1.16) correlated well with their 2T4k_VB counterparts. RPM (controls: 1%, AD: 3%), rLogan (controls: 1%, AD: 3%) and SUVr(50–70) (controls: 3%, AD: 8%) showed an excellent TRT reliability. In conclusion, most parametric methods showed excellent performance for [18F]florbetapir, but RPM and rLogan seem the methods of choice, combining the highest accuracy and best TRT reliability.

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Comparison of [11C]UCB-J and [18F]FDG PET in Alzheimer’s disease: A tracer kinetic modeling study

Journal of Cerebral Blood Flow & Metabolism ◽

10.1177/0271678x211004312 ◽

2021 ◽

pp. 0271678X2110043

Author(s):

Ming-Kai Chen ◽

Adam P Mecca ◽

Mika Naganawa ◽

Jean-Dominique Gallezot ◽

Takuya Toyonaga ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Medial Temporal Lobe ◽

Brain Regions ◽

Volume Of Distribution ◽

Synaptic Density ◽

Cognitively Normal ◽

Tracer Kinetic ◽

Suitable Marker

[11C]UCB-J PET for synaptic vesicle glycoprotein 2 A (SV2A) has been proposed as a suitable marker for synaptic density in Alzheimer’s disease (AD). We compared [11C]UCB-J binding for synaptic density and [18F]FDG uptake for metabolism (correlated with neuronal activity) in 14 AD and 11 cognitively normal (CN) participants. We assessed both absolute and relative outcome measures in brain regions of interest, i.e., K1 or R1 for [11C]UCB-J perfusion, VT (volume of distribution) or DVR to cerebellum for [11C]UCB-J binding to SV2A; and Ki or Ki R to cerebellum for [18F]FDG metabolism. [11C]UCB-J binding and [18F]FDG metabolism showed a similar magnitude of reduction in the medial temporal lobe of AD –compared to CN participants. However, the magnitude of reduction of [11C]UCB-J binding in neocortical regions was less than that observed with [18F]FDG metabolism. Inter-tracer correlations were also higher in the medial temporal regions between synaptic density and metabolism, with lower correlations in neocortical regions. [11C]UCB-J perfusion showed a similar pattern to [18F]FDG metabolism, with high inter-tracer regional correlations. In summary, we conducted the first in vivo PET imaging of synaptic density and metabolism in the same AD participants and reported a concordant reduction in medial temporal regions but a discordant reduction in neocortical regions.

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Quantitative Methods for the Detection of Tau Seeding Activity in Human Biofluids

Frontiers in Neuroscience ◽

10.3389/fnins.2021.654176 ◽

2021 ◽

Vol 15 ◽

Author(s):

Aurelien Lathuiliere ◽

Bradley T. Hyman

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Clinical Data ◽

Quantitative Methods ◽

Brain Regions ◽

Next Generation ◽

Human Samples

The ability of tau aggregates to recruit and misfold monomeric tau and propagate across brain regions has been studied extensively and is now recognized as a critical pathological step in Alzheimer’s disease (AD) and other tauopathies. Recent evidence suggests that the detection of tau seeds in human samples may be relevant and correlate with clinical data. Here, we review the available methods for the measurement of such tau seeds, their limitations and their potential implementation for the development of the next-generation biomarkers.

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Tau pathology in cognitively normal older adults

10.1101/611186 ◽

2019 ◽

Author(s):

Jacob Ziontz ◽

Murat Bilgel ◽

Andrea T. Shafer ◽

Abhay Moghekar ◽

Wendy Elkins ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Memory Performance ◽

Brain Regions ◽

Tau Pathology ◽

Cognitively Normal ◽

Rates Of Change ◽

Baltimore Longitudinal Study ◽

Brain Changes ◽

Male Sex

AbstractINTRODUCTIONTau pathology, a hallmark of Alzheimer’s disease, is observed in the brains of virtually all individuals over 70.METHODSUsing 18F-AV-1451 (18F-flortaucipir) PET, we evaluated tau pathology in 54 cognitively normal participants (mean age 77.5, SD 8.9) from the Baltimore Longitudinal Study of Aging. We assessed associations between PET signal and age, sex, race, and amyloid positivity. We investigated relationships between regional signal and retrospective rates of change in regional volumes and cognitive function adjusting for age, sex, and amyloid status.RESULTSGreater age, male sex, black race, and amyloid positivity were associated with higher 18F-AV-1451 retention in distinct brain regions. Retention in the entorhinal cortex was associated with lower entorhinal volume (β = −1.124, SE = 0.485, p = 0.025) and a steeper decline in memory performance (β = −0.086, SE = 0.039, p = 0.029).DISCUSSIONAssessment of medial temporal tau pathology will provide insights into early structural brain changes associated with later cognitive impairment and Alzheimer’s disease.

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The Evaluation of Tau Deposition with [18F]PI-2620 by Using a Semiquantitative Method in Cognitively Normal Subjects and Patients with Mild Cognitive Impairment and Alzheimer’s Disease

Molecular Imaging ◽

10.1155/2021/6640054 ◽

2021 ◽

Vol 2021 ◽

pp. 1-8

Author(s):

Attapon Jantarato ◽

Sira Vachatimanont ◽

Natphimol Boonkawin ◽

Sukanya Yaset ◽

Anchisa Kunawudhi ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Parietal Lobe ◽

Standardized Uptake Value ◽

Occipital Lobe ◽

Normal Subjects ◽

Semiquantitative Analysis ◽

Cognitively Normal

Background. Some studies have reported the effectiveness of [18F]PI-2620 as an effective tau-binding radiotracer; however, few reports have applied semiquantitative analysis to the tracer. Therefore, this study’s aim was to perform a semiquantitative analysis of [18F]PI-2620 in individuals with normal cognition and patients with mild cognitive impairment (MCI) and Alzheimer’s disease (AD). Methods. Twenty-six cognitively normal (CN) subjects, 7 patients with AD, and 36 patients with MCI were enrolled. A dynamic positron emission tomography (PET) scan was performed 30–75 min postinjection. PET and T1-weighted magnetic resonance imaging scans were coregistered. The standardized uptake value ratio (SUVr) was used for semiquantitative analysis. The P-Mod software was applied to create volumes of interest. The ANOVA and post hoc Tukey HSD were used for statistical analysis. Results. In the AD group, the occipital lobe had a significantly higher mean SUVr ( 1.46 ± 0.57 ) than in the CN and MCI groups. Compared with the CN group, the AD group showed significantly higher mean SUVr in the fusiform gyrus ( 1.06 ± 0.09 vs. 1.49 ± 0.86 ), inferior temporal ( 1.07 ± 0.07 vs. 1.46 ± 0.08 ), parietal lobe, lingual gyrus, and precuneus regions. Similarly, the AD group demonstrated a higher mean SUVr than the MCI group in the precuneus, lingual, inferior temporal, fusiform, supramarginal, orbitofrontal, and superior temporal regions. The remaining observed regions, including the striatum, basal ganglia, thalamus, and white matter, showed a low SUVr across all groups with no statistically significant differences. Conclusion. A significantly higher mean SUVr of [18F]PI-2620 was observed in the AD group; a significant area of the brain in the AD group demonstrated tau protein deposit in concordance with Braak Stages III–V, providing useful information to differentiate AD from CN and MCI. Moreover, the low SUVr in the deep striatum and thalamus could be useful for excluding primary tauopathies.

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Feasibility study of amyloid PET-only quantification; a comparison with visual interpretation.

10.21203/rs.2.23805/v1 ◽

2020 ◽

Author(s):

Natsumi Shimokawa ◽

Go Akamatsu ◽

Miyako Kadosaki ◽

Masayuki Sasaki

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Quantitative Evaluation ◽

Quantitative Methods ◽

Standardized Uptake Value ◽

Amyloid Pet ◽

Visual Interpretation ◽

Visual Evaluation ◽

Quantification Method ◽

Sensitivity Specificity

Abstract Objective Visual evaluation is the standard for amyloid positron emission tomography (PET) examination, though the result depends upon the physician’s subjective review of the images. Therefore, objective quantitative evaluation is expected to be useful for image interpretation. In this study, we examined the usefulness of the quantitative evaluation of amyloid PET using a PET-only quantification method in comparison with visual evaluation. Methods A total of 166 individuals, including 58 cognitively normal controls, 62 individuals with mild cognitive impairment, and 46 individuals with early Alzheimer’s disease, were retrospectively investigated. They underwent 11C-Pittsburgh compound-B (PiB) PET examination through the Japanese-Alzheimer’s disease neuroimaging initiative (J-ADNI). Amyloid accumulation in cerebral cortices was assessed using visual and quantitative methods. The quantitative evaluation was performed using the adaptive template method and empirically PiB-prone region of interest, and the standardized uptake value ratio (SUVR) in each area was obtained. Results Visual evaluation and SUVR were significantly correlated in the cerebral cortices (ρ = 0.85–0.87; p < 0.05). In visual evaluation, the sensitivity, specificity, and accuracy were 78%, 76%, and 77%, respectively. Meanwhile, for quantitative evaluation, the sensitivity, specificity, and accuracy were 78%, 76%, and 77%, in mean cortical SUVR (mcSUVR) and 79%, 79%, and 79% in maximum SUVR (maxSUVR), respectively. Conclusion The PET-only quantification method resulted in a concordant result with visual evaluation and was considered to be useful for amyloid PET.

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