Evaluation of a visual interpretation method for tau‐PET with 18F‐flortaucipir

Abstract Introduction Positron emission tomography targeting tau (tau‐PET) is a promising diagnostic tool for the identification of Alzheimer's disease (AD). Currently available data rely on quantitative measures, and a visual interpretation method, critical for clinical translation, is needed. Methods We developed a visual interpretation method for 18F‐flortaucipir tau‐PET and tested it on 274 individuals (cognitively normal controls, patients with mild cognitive impairment [MCI], AD dementia, and non‐AD diagnoses). Two readers interpreted 18F‐flortaucipir PET using two complementary indices: a global visual score and a visual distribution pattern. Results Global visual scores were reliable, correlated with global cortical 18F‐flortaucipir standardized uptake value ratio (SUVR) and were associated with clinical diagnosis and amyloid status. The AD‐like 18F‐flortaucipir pattern had good sensitivity and specificity to identify amyloid‐positive patients with AD dementia or MCI. Discussion This 18F‐flortaucipir visual rating scheme is associated with SUVR quantification, clinical diagnosis, and amyloid status, and constitutes a promising approach to tau measurement in clinical settings.

[1]  Jesse A. Brown,et al.  Prospective longitudinal atrophy in Alzheimer’s disease correlates with the intensity and topography of baseline tau-PET , 2020, Science Translational Medicine.

[2]  B. Miller,et al.  Discriminative Accuracy of [18F]flortaucipir Positron Emission Tomography for Alzheimer Disease vs Other Neurodegenerative Disorders , 2018, JAMA.

[3]  Julie Gonneaud,et al.  Characterization of Alzheimer Disease Biomarker Discrepancies Using Cerebrospinal Fluid Phosphorylated Tau and AV1451 Positron Emission Tomography. , 2020, JAMA neurology.

[4]  Seong-Min Choi,et al.  Primary Age-Related Tauopathy: An Elderly Brain Pathology Frequently Encountered during Autopsy , 2019, Journal of pathology and translational medicine.

[5]  J. Morris,et al.  The diagnosis of dementia due to Alzheimer’s disease: Recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer's disease , 2011, Alzheimer's & Dementia.

[6]  A. Joshi,et al.  Regional profiles of the candidate tau PET ligand 18F-AV-1451 recapitulate key features of Braak histopathological stages. , 2016, Brain : a journal of neurology.

[7]  William J. Jagust,et al.  Effect of Off-Target Binding on 18F-Flortaucipir Variability in Healthy Controls Across the Life Span , 2019, The Journal of Nuclear Medicine.

[8]  Daniel R. Schonhaut,et al.  Tau pathology and neurodegeneration contribute to cognitive impairment in Alzheimer’s disease , 2017, Brain : a journal of neurology.

[9]  H. Braak,et al.  Neuropathological stageing of Alzheimer-related changes , 2004, Acta Neuropathologica.

[10]  David Berron,et al.  Alzheimer's pathology targets distinct memory networks in the ageing brain. , 2019, Brain : a journal of neurology.

[11]  V. Libri,et al.  PIB is a non-specific imaging marker of amyloid-beta (Abeta) peptide-related cerebral amyloidosis. , 2007, Brain : a journal of neurology.

[12]  H. Braak,et al.  Staging of Alzheimer disease-associated neurofibrillary pathology using paraffin sections and immunocytochemistry , 2006, Acta Neuropathologica.

[13]  Elizabeth C Mormino,et al.  Not quite PIB-positive, not quite PIB-negative: Slight PIB elevations in elderly normal control subjects are biologically relevant , 2012, NeuroImage.

[14]  Charles DeCarli,et al.  Existing Pittsburgh Compound-B positron emission tomography thresholds are too high: statistical and pathological evaluation. , 2015, Brain : a journal of neurology.

[15]  Jorge Sepulcre,et al.  Fluorodeoxyglucose metabolism associated with tau‐amyloid interaction predicts memory decline , 2017, Annals of neurology.

[16]  Keith A. Johnson,et al.  Validating novel tau positron emission tomography tracer [F‐18]‐AV‐1451 (T807) on postmortem brain tissue , 2015, Annals of neurology.

[17]  M. Mintun,et al.  Amyloid-β Imaging with Pittsburgh Compound B and Florbetapir: Comparing Radiotracers and Quantification Methods , 2013, The Journal of Nuclear Medicine.

[18]  Clifford R. Jack,et al.  An autoradiographic evaluation of AV-1451 Tau PET in dementia , 2016, Acta Neuropathologica Communications.

[19]  Otakar Belohlavek,et al.  Improved beta-amyloid PET reproducibility using two-phase acquisition and grey matter delineation , 2018, European Journal of Nuclear Medicine and Molecular Imaging.

[20]  R. Coleman,et al.  Use of florbetapir-PET for imaging beta-amyloid pathology. , 2011, JAMA.

[21]  H. Kolb,et al.  [18F]T807, a novel tau positron emission tomography imaging agent for Alzheimer's disease , 2013, Alzheimer's & Dementia.

[22]  A. Chincarini,et al.  Semi-quantification and grading of amyloid PET: A project of the European Alzheimer's Disease Consortium (EADC) , 2019, NeuroImage: Clinical.

[23]  J. Barrio,et al.  The Irony of PET Tau Probe Specificity , 2018, The Journal of Nuclear Medicine.

[24]  Val J Lowe,et al.  Positron Emission Tomography Imaging With [18F]flortaucipir and Postmortem Assessment of Alzheimer Disease Neuropathologic Changes. , 2020, JAMA neurology.

[25]  W. Klunk,et al.  Imaging brain amyloid in Alzheimer's disease with Pittsburgh Compound‐B , 2004, Annals of neurology.

[26]  Gil D Rabinovici,et al.  Associations between [18F]AV1451 tau PET and CSF measures of tau pathology in a clinical sample , 2017, Neurology.

[27]  John Seibyl,et al.  Cerebral amyloid-β PET with florbetaben (18F) in patients with Alzheimer's disease and healthy controls: a multicentre phase 2 diagnostic study , 2011, The Lancet Neurology.

[28]  William J. Jagust,et al.  Comparison of multiple tau-PET measures as biomarkers in aging and Alzheimer's disease , 2017, NeuroImage.

[29]  W. Jagust,et al.  Association of lifetime cognitive engagement and low β-amyloid deposition. , 2012, Archives of neurology.

[30]  Gil D Rabinovici,et al.  Elevated 18F-AV-1451 PET tracer uptake detected in incidental imaging findings , 2017, Neurology.

[31]  Barbara Borroni,et al.  Faculty Opinions recommendation of 18F-flortaucipir (AV-1451) tau PET in frontotemporal dementia syndromes. , 2019 .

[32]  Bradford C. Dickerson,et al.  Diagnostic value of plasma phosphorylated tau181 in Alzheimer’s disease and frontotemporal lobar degeneration , 2020, Nature Medicine.

[33]  Hitoshi Shimada,et al.  Impact of spillover from white matter by partial volume effect on quantification of amyloid deposition with [11C]PiB PET , 2016, NeuroImage.

[34]  O. Hansson,et al.  18F-Flortaucipir in TDP-43 associated frontotemporal dementia , 2019, Scientific Reports.

[35]  Janna H. Neltner,et al.  Primary age-related tauopathy (PART): a common pathology associated with human aging , 2014, Acta Neuropathologica.

[36]  C. Jack,et al.  NIA-AA Research Framework: Toward a biological definition of Alzheimer’s disease , 2018, Alzheimer's & Dementia.

[37]  Daniel R. Schonhaut,et al.  PET Imaging of Tau Deposition in the Aging Human Brain , 2016, Neuron.

[38]  W. Jagust,et al.  Considerations and code for partial volume correcting [18F]-AV-1451 tau PET data , 2017, Data in brief.

[39]  Hanna Cho,et al.  In vivo cortical spreading pattern of tau and amyloid in the Alzheimer disease spectrum , 2016, Annals of neurology.

[40]  C. Jack,et al.  Strategic roadmap for an early diagnosis of Alzheimer's disease based on biomarkers , 2017, The Lancet Neurology.

[41]  M. Frosch,et al.  [F-18]-AV-1451 binding correlates with postmortem neurofibrillary tangle Braak staging , 2017, Acta Neuropathologica.

[42]  R. Coleman,et al.  Cerebral PET with florbetapir compared with neuropathology at autopsy for detection of neuritic amyloid-β plaques: a prospective cohort study , 2012, The Lancet Neurology.

[43]  Takamichi Murakami,et al.  Investigation of 11C-PiB equivocal PET findings , 2015, Annals of Nuclear Medicine.

[44]  Elisabet Englund,et al.  Correlation of In Vivo [18F]Flortaucipir With Postmortem Alzheimer Disease Tau Pathology , 2019, JAMA neurology.

[45]  Maria Luisa Gorno-Tempini,et al.  18F-flortaucipir (AV-1451) tau PET in frontotemporal dementia syndromes , 2019, Alzheimer's Research & Therapy.

[46]  E. Salmon,et al.  18F‐flutemetamol amyloid imaging in Alzheimer disease and mild cognitive impairment: A phase 2 trial , 2010, Annals of neurology.

[47]  E. Vidoni,et al.  Augmenting amyloid PET interpretations with quantitative information improves consistency of cerebral amyloid detection , 2015, Alzheimer's & Dementia.

[48]  Frederik Barkhof,et al.  Atrophy patterns in early clinical stages across distinct phenotypes of Alzheimer's disease , 2015, Human brain mapping.

[49]  A. Nordberg,et al.  Tau PET imaging in neurodegenerative tauopathies—still a challenge , 2019, Molecular Psychiatry.