In Vivo Head-to-Head Comparison of [F]GTP1 with [F]MK-6240 and [F]PI-2620 in Alzheimer Disease.

Alzheimer disease (AD) is characterized by the accumulation of tau neurofibrillary tangles that can be labeled with PET tracers. Multiple tau PET tracers have been used in clinical studies, including [F]GTP1, [F]PI-2620, and [F]MK-6240. Standardized harmonization scales for comparing tau PET signals across tracers are currently under development and can be informed by comparisons of signals between tracers in both target and off-target regions of the brain.

Head-to-head comparison of tau PET tracers [F]PI-2620 and [F]RO948 in non-demented individuals with brain amyloid deposition: the TAU-PET FACEHBI cohort.

Background: Second-generation tau tracers for positron emission tomography (PET) show high affinity for paired helical filaments tau deposits characteristic of Alzheimer´s disease and low off-target binding. Differences in their chemical structure though may lead to variations in their regional tau uptake and off-target signal. In this work, we aimed to compare the in-vivo uptake of tau tracers [F]PI-2620 and [F]RO948 in the early stages of the AD continuum.

Harmonizing tau positron emission tomography in Alzheimer's disease: The CenTauR scale and the joint propagation model.

Introduction: Tau-positron emission tomography (PET) outcome data of patients with Alzheimer's disease (AD) cannot currently be meaningfully compared or combined when different tracers are used due to differences in tracer properties, instrumentation, and methods of analysis.

Methods: Using head-to-head data from five cohorts with tau PET radiotracers designed to target tau deposition in AD, we tested a joint propagation model (JPM) to harmonize quantification (units termed "CenTauR" [CTR]). JPM is a statistical model that simultaneously models the relationships between head-to-head and anchor point data.

At-Home Administration of Gantenerumab by Care Partners to People with Early Alzheimer's Disease: Feasibility, Safety and Pharmacodynamic Impact.

Background: Monoclonal antibodies that target amyloid-beta and remove amyloid plaques can slow cognitive and functional decline in early Alzheimer's disease. Gantenerumab is a subcutaneously administered fully-human anti-amyloid-beta monoclonal antibody with highest affinity for aggregated amyloid-beta. Since the phase 3 GRADUATE trials did not meet the primary endpoint (change from baseline to Week 116 in Clinical Dementia Rating scale - Sum of Boxes), development of gantenerumab in sporadic Alzheimer's disease was stopped and all ongoing trials were terminated early due to sponsor decision.

Combined in vivo MRI assessment of locus coeruleus and nucleus basalis of Meynert integrity in amnestic Alzheimer's disease, suspected-LATE and frontotemporal dementia.

Background: The locus coeruleus (LC) and the nucleus basalis of Meynert (NBM) are altered in early stages of Alzheimer's disease (AD). Little is known about LC and NBM alteration in limbic-predominant age-related TDP-43 encephalopathy (LATE) and frontotemporal dementia (FTD). The aim of the present study is to investigate in vivo LC and NBM integrity in patients with suspected-LATE, early-amnestic AD and FTD in comparison with controls.

Evaluation of partial volume correction and analysis of longitudinal [F]GTP1 tau PET imaging in Alzheimer's disease using linear mixed-effects models.

Purpose: We evaluated the impact of partial volume correction (PVC) methods on the quantification of longitudinal [F]GTP1 tau positron-emission tomography (PET) in Alzheimer's disease and the suitability of describing the tau pathology burden temporal trajectories using linear mixed-effects models (LMEM).

Methods: We applied van Cittert iterative deconvolution (VC), 2-compartment, and 3-compartment, and the geometric transfer matrix plus region-based voxelwise methods to data acquired in an Alzheimer's disease natural history study over 18 months at a single imaging site. We determined the optimal PVC method by comparing the standardized uptake value ratio change (%ΔSUVR) between diagnostic and tau burden-level groups and the longitudinal repeatability derived from the LMEM.

Comparison of Group-Level and Individualized Brain Regions for Measuring Change in Longitudinal Tau Positron Emission Tomography in Alzheimer Disease.

Importance: Longitudinal tau positron emission tomography (PET) is a relevant outcome in clinical trials evaluating disease-modifying therapies in Alzheimer disease (AD). A key unanswered question is whether the use of participant-specific (individualized) regions of interest (ROIs) is superior to conventional approaches where the same ROI (group-level) is used for each participant.

Objective: To compare group- and participant-level ROIs in participants at different stages of the AD clinical continuum in terms of annual percentage change in tau-PET standardized uptake value ratio (SUVR) and sample size requirements.

Could tau-PET imaging contribute to a better understanding of the different patterns of clinical progression in Alzheimer's disease? A 2-year longitudinal study.

Background: Monitoring the progression of Tau pathology makes it possible to study the clinical diversity of Alzheimer's disease. In this 2-year longitudinal PET study, we aimed to determine the progression of [F]-flortaucipir binding and of cortical atrophy, and their relationships with cognitive decline.

Methods: Twenty-seven AD patients at the mild cognitive impairment/mild dementia stages and twelve amyloid-negative controls underwent a neuropsychological assessment, 3 T brain MRI, and [F]-flortaucipir PET imaging (Tau1) and were monitored annually over 2 years with a second brain MRI and tau-PET imaging after 2 years (Tau2).

Positron Emission Tomography with [ F]-DPA-714 Unveils a Smoldering Component in Most Multiple Sclerosis Lesions which Drives Disease Progression.

Objective: To determine the prognostic value of persisting neuroinflammation in multiple sclerosis (MS) lesions, we developed a 18 kDa-translocator-protein-positron emission tomography (PET) -based classification of each lesion according to innate immune cell content and localization. We assessed the respective predictive value of lesion phenotype and diffuse inflammation on atrophy and disability progression over 2 years.

Methods: Thirty-six people with MS (disease duration 9 ± 6 years; 12 with relapsing-remitting, 13 with secondary-progressive, and 11 with primary-progressive) and 19 healthy controls (HCs) underwent a dynamic [ F]-DPA-714-PET.

PET-BIDS, an extension to the brain imaging data structure for positron emission tomography.

The Brain Imaging Data Structure (BIDS) is a standard for organizing and describing neuroimaging datasets, serving not only to facilitate the process of data sharing and aggregation, but also to simplify the application and development of new methods and software for working with neuroimaging data. Here, we present an extension of BIDS to include positron emission tomography (PET) data, also known as PET-BIDS, and share several open-access datasets curated following PET-BIDS along with tools for conversion, validation and analysis of PET-BIDS datasets.

Spontaneous remyelination in lesions protects the integrity of surrounding tissues over time in multiple sclerosis.

Background And Purpose: Lesion remyelination preserves axonal integrity in animal models of multiple sclerosis (MS), but an in vivo demonstration of its protective effect on surrounding tissues in humans is lacking.

Methods: Nineteen persons with MS were enrolled in a cohort study and underwent two positron emission tomography (PET)/magnetic resonance imaging (MRI) scans 1-4 months apart. Voxelwise maps of Pittsburgh compound B distribution volume ratio, reflecting myelin content, were used to calculate an index of baseline demyelination, and of dynamic demyelination and remyelination over the follow-up in 549 single white matter lesions.

Distinct amyloid and tau PET signatures are associated with diverging clinical and imaging trajectories in patients with amnestic syndrome of the hippocampal type.

We aimed to investigate the amyloid and tau PET imaging signatures of patients with amnestic syndrome of the hippocampal type (ASHT) and study their clinical and imaging progression according to their initial PET imaging status. Thirty-six patients with a progressive ASHT and 30 controls underwent a complete neuropsychological assessment, 3 T brain MRI, [C]-PiB and [F]-Flortaucipir PET imaging. Subjects were clinically followed-up annually over 2 years, with a second 3 T MRI (n = 27 ASHT patients, n = 28 controls) and tau-PET (n = 20 ASHT patients) at the last visit.

Choroid Plexus Enlargement in Inflammatory Multiple Sclerosis: 3.0-T MRI and Translocator Protein PET Evaluation.

Background Choroid plexuses (CPs) have been suggested as a key gateway for inflammation in experimental autoimmune encephalitis, but in vivo evidence of their involvement in multiple sclerosis (MS) is lacking. Purpose To assess CP volumetric and inflammatory changes in patients with MS versus healthy control participants. Materials and Methods This was a secondary analysis of 97 patients (61 with relapsing-remitting MS [RRMS] and 36 with progressive MS) and 44 healthy control participants who participated in three prospective 3.

Supervised clustering for TSPO PET imaging.

Purpose: This technical note seeks to act as a practical guide for implementing a supervised clustering algorithm (SVCA) reference region approach and to explain the main strengths and limitations of the technique in the context of 18-kilodalton translocator protein (TSPO) positron emission tomography (PET) studies in experimental medicine.

Background: TSPO PET is the most widely used imaging technique for studying neuroinflammation in vivo in humans. Quantifying neuroinflammation with PET can be a challenging and invasive procedure, especially in frail patients, because it often requires blood sampling from an arterial catheter.

Structural and Clinical Correlates of a Periventricular Gradient of Neuroinflammation in Multiple Sclerosis.

Objectives: To explore in vivo innate immune cell activation as a function of the distance from ventricular CSF in patients with multiple sclerosis (MS) using [F]-DPA714 PET and to investigate its relationship with periventricular microstructural damage, evaluated by magnetization transfer ratio (MTR), and with trajectories of disability worsening.

Methods: Thirty-seven patients with MS and 19 healthy controls underwent MRI and [F]-DPA714 TSPO dynamic PET, from which individual maps of voxels characterized by innate immune cell activation (DPA+) were generated. White matter (WM) was divided in 3-mm-thick concentric rings radiating from the ventricular surface toward the cortex, and the percentage of DPA+ voxels and mean MTR were extracted from each ring.

Pharmacokinetic neuroimaging to study the dose-related brain kinetics and target engagement of buprenorphine in vivo.

A wide range of buprenorphine doses are used for either pain management or maintenance therapy in opioid addiction. The complex in vitro profile of buprenorphine, with affinity for µ-, δ-, and κ-opioid receptors (OR), makes it difficult to predict its dose-related neuropharmacology in vivo. In rats, microPET imaging and pretreatment by OR antagonists were performed to assess the binding of radiolabeled buprenorphine (microdose C-buprenorphine) to OR subtypes in vivo (n = 4 per condition).

Increased microglial activation in patients with Parkinson disease using [F]-DPA714 TSPO PET imaging.

Introduction: Increasing evidence suggests that neuroinflammation is active in Parkinson disease (PD) and contributes to neurodegeneration. This process can be studied in vivo with PET and radioligands targeting TSPO, upregulated in activated microglia. Initial PET studies investigating microglial activation in PD with the [C]-PK11195 have provided inconclusive results.

Predicting PET-derived myelin content from multisequence MRI for individual longitudinal analysis in multiple sclerosis.

Multiple sclerosis (MS) is a demyelinating and inflammatory disease of the central nervous system (CNS). The demyelination process can be repaired by the generation of a new sheath of myelin around the axon, a process termed remyelination. In MS patients, the demyelination-remyelination cycles are highly dynamic.