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.

Mitochondrial complex I density is associated with IQ and cognition in cognitively healthy adults: an in vivo [F]BCPP-EF PET study.

Background: Mitochondrial function plays a key role in regulating neurotransmission and may contribute to general intelligence. Mitochondrial complex I (MC-I) is the largest enzyme of the respiratory chain. Recently, it has become possible to measure MC-I distribution in vivo, using a novel positron emission tomography tracer [F]BCPP-EF, thus, we set out to investigate the association between MC-I distribution and measures of cognitive function in the living healthy brain.

Validation of quantitative assessment of florbetaben PET scans as an adjunct to the visual assessment across 15 software methods.

Purpose: Amyloid positron emission tomography (PET) with [F]florbetaben (FBB) is an established tool for detecting Aβ deposition in the brain in vivo based on visual assessment of PET scans. Quantitative measures are commonly used in the research context and allow continuous measurement of amyloid burden. The aim of this study was to demonstrate the robustness of FBB PET quantification.

A Visual Interpretation Algorithm for Assessing Brain Tauopathy with F-MK-6240 PET.

In vivo characterization of pathologic deposition of tau protein in the human brain by PET imaging is a promising tool in drug development trials of Alzheimer disease (AD). 6-(fluoro-F)-3-(1H-pyrrolo[2,3-c]pyridin-1-yl)isoquinolin-5-amine (F-MK-6240) is a radiotracer with high selectivity and subnanomolar affinity for neurofibrillary tangles that shows favorable nonspecific brain penetration and excellent kinetic properties. The purpose of the present investigation was to develop a visual assessment method that provides both an overall assessment of brain tauopathy and regional characterization of abnormal tau deposition.

Boosting the diagnostic power of amyloid-β PET using a data-driven spatially informed classifier for decision support.

Background: Amyloid-β (Aβ) PET has emerged as clinically useful for more accurate diagnosis of patients with cognitive decline. Aβ deposition is a necessary cause or response to the cellular pathology of Alzheimer's disease (AD). Usual clinical and research interpretation of amyloid PET does not fully utilise all information regarding the spatial distribution of signal.

Reproducibility of findings in modern PET neuroimaging: insight from the NRM2018 grand challenge.

The reproducibility of findings is a compelling methodological problem that the neuroimaging community is facing these days. The lack of standardized pipelines for image processing, quantification and statistics plays a major role in the variability and interpretation of results, even when the same data are analysed. This problem is well-known in MRI studies, where the indisputable value of the method has been complicated by a number of studies that produce discrepant results.

A multisite analysis of the concordance between visual image interpretation and quantitative analysis of [F]flutemetamol amyloid PET images.

Background: [F]flutemetamol PET scanning provides information on brain amyloid load and has been approved for routine clinical use based upon visual interpretation as either negative (equating to none or sparse amyloid plaques) or amyloid positive (equating to moderate or frequent plaques). Quantitation is however fundamental to the practice of nuclear medicine and hence can be used to supplement amyloid reading methodology especially in unclear cases.

Methods: A total of 2770 [F]flutemetamol images were collected from 3 clinical studies and 6 research cohorts with available visual reading of [F]flutemetamol and quantitative analysis of images.

Tau: A Canonical Image Based Algorithm to Quantify Tau PET Scans.

Recently, Amyloid was introduced as a new canonical image-based algorithm to quantify amyloid PET scans and demonstrated increased power over traditional SUV ratio (SUVR) approaches when assessed in cross-sectional and longitudinal analyses. We build further on this mathematical framework to develop a Tau algorithm for the quantitative analysis of the more complex spatial distribution displayed by tau PET radiotracers. Cross-sectional ( = 615) and longitudinal ( = 149) F-flortaucipir data were obtained from the Alzheimer's Disease Neuroimaging Initiative along with necessary adjunct amyloid PET and T1-weighted structural MRI data.

Nonlinear biomarker interactions in conversion from mild cognitive impairment to Alzheimer's disease.

Multiple biomarkers can capture different facets of Alzheimer's disease. However, statistical models of biomarkers to predict outcomes in Alzheimer's rarely model nonlinear interactions between these measures. Here, we used Gaussian Processes to address this, modelling nonlinear interactions to predict progression from mild cognitive impairment (MCI) to Alzheimer's over 3 years, using Alzheimer's Disease Neuroimaging Initiative (ADNI) data.

In vivo detection of cerebral tau pathology in long-term survivors of traumatic brain injury.

Traumatic brain injury (TBI) can trigger progressive neurodegeneration, with tau pathology seen years after a single moderate-severe TBI. Identifying this type of posttraumatic pathology in vivo might help to understand the role of tau pathology in TBI pathophysiology. We used flortaucipir positron emission tomography (PET) to investigate whether tau pathology is present many years after a single TBI in humans.

Dopamine D2/D3 receptor abnormalities after traumatic brain injury and their relationship to post-traumatic depression.

Objective: To investigate dopamine D2/D3 receptor availability following traumatic brain injury (TBI) and their relationship to the presence of DSM-IV Major Depressive Disorder (MDD) and patterns of axonal injury.

Methods: Twelve moderate-severe TBI patients and 26 controls were imaged using [C]PHNO positron emission tomography (PET) and structural magnetic resonance imaging (MRI). TBI patients and a second group of 32 controls also underwent diffusion tensor imaging (DTI) and neuropsychological assessment.

Amyloid Load: A More Sensitive Biomarker for Amyloid Imaging.

Amyloid-β (Aβ) plays a key role in the pathogenesis of Alzheimer disease (AD) and can be imaged in vivo using F-florbetapir PET. A composite SUV ratio (SUVr) is a commonly used outcome measure for quantifying the global Aβ burden; however, sensitivity is suboptimal and can lead to low power in clinical trials. We introduce amyloid load, Aβ, as a novel biomarker to quantify the global Aβ burden along with an automated algorithm for its calculation (Amyloid).

Imaging Aβ and tau in early stage Alzheimer's disease with [F]AV45 and [F]AV1451.

Background: AD is a progressive neurodegenerative disorder that is associated with the accumulation of two different insoluble protein aggregates, Aβ plaques and hyperphosphorylated tau. This study aimed to investigate the optimal acquisition and quantification of [F]AV45 and [F]AV1451 to image Aβ and tau, respectively, in subjects with AD. Fifteen subjects with early stage AD underwent a T1-weighted structural MRI and two dynamic PET scans to image Aβ (60 min, [F]AV45) and tau (120 min, [F]AV1451).

Spatiotemporal Distribution of β-Amyloid in Alzheimer Disease Is the Result of Heterogeneous Regional Carrying Capacities.

β-amyloid (Aβ) accumulation in the brain is 1 of 2 pathologic hallmarks of Alzheimer disease (AD), and the spatial distribution of Aβ has been studied extensively ex vivo. We applied mathematical modeling to Aβ in vivo PET imaging data to investigate competing theories of Aβ spread in AD. Our results provided evidence that Aβ accumulation starts in all brain regions simultaneously and that its spatiotemporal distribution is due to heterogeneous regional carrying capacities (regional maximum possible concentration of Aβ) for the aggregated protein rather than to longer-term spreading from seed regions.

Effects of mannose-6-phosphate on human fibroblast cells - biomed 2010.

Coordinate expression of CTGF and TGF-ss plays an important role in tissue fibrosis. Expression of these factors is increased under hypoxic conditions. Treatment of cells under hypoxic conditions with fructose-1,6-bisphosphate has been previously shown to decrease production of CTGF [1].

Defining the role of hif-1 ? And ctgf in fibrosis - biomed 2009.

Connective tissue growth factor (CTGF) plays a major role in pathways that lead to fibrosis, including fibrosis of major organs, fibroproliferative diseases, and scarring. Tissue hypoxia has been reported to induce the expression and secretion of CTGF in various tissues and organs, such as in renal cortical myofibroblasts, in renal interstitial fibroblasts, and in skin. This implicates CTGF as a mechanism of action for tissue damage caused by hypoxia.

Changes to open field surfaces typically used to elicit hippocampal remapping elicit graded exploratory responses.

Studies show that changes in environmental context alter the spatial firing patterns ('remapping') and increase immediate early gene activation in hippocampal but not subicular neurons. However, such studies rarely report co-occurring behavioural responses. We examined the behavioural effects of habituating rats to a walled open field, and then of changing the environmental context by altering wall patterns and floor colour.