Biomarkers.

Background: A novel method using diffusion-weighted imaging (DWI) allows for assessing microstructural injury in the gray matter by measuring cortical mean diffusivity (cMD). Previous studies have shown that altered cMD is related to amyloid (Aβ) cross-sectionally and can predict longitudinal cognitive decline and clinical progression, suggesting utility in clinical trials. However, the longitudinal associations between these measures are unknown.

Contribution of extracerebral tracer retention and partial volume effects to sex differences in Flortaucipir-PET signal.

Clinically normal females exhibit higher F-flortaucipir (FTP)-PET signal than males across the cortex. However, these sex differences may be explained by neuroimaging idiosyncrasies such as off-target extracerebral tracer retention or partial volume effects (PVEs). 343 clinically normal participants (female = 58%; mean[SD]=73.

Cortical microstructural changes predict tau accumulation and episodic memory decline in older adults harboring amyloid.

Introduction: Non-invasive diffusion-weighted imaging (DWI) to assess brain microstructural changes via cortical mean diffusivity (cMD) has been shown to be cross-sectionally associated with tau in cognitively normal older adults, suggesting that it might be an early marker of neuronal injury. Here, we investigated how regional cortical microstructural changes measured by cMD are related to the longitudinal accumulation of regional tau as well as to episodic memory decline in cognitively normal individuals harboring amyloid pathology.

Methods: 122 cognitively normal participants from the Harvard Aging Brain Study underwent DWI, T1w-MRI, amyloid and tau PET imaging, and Logical Memory Delayed Recall (LMDR) assessments.

Impact of motion correction on [F]-MK6240 tau PET imaging.

. Positron emission tomography (PET) imaging of tau deposition using [F]-MK6240 often involves long acquisitions in older subjects, many of whom exhibit dementia symptoms. The resulting unavoidable head motion can greatly degrade image quality.

Measurement of Cerebral Perfusion Indices from the Early Phase of [F]MK6240 Dynamic Tau PET Imaging.

6-(fluoro-F)-3-(1H-pyrrolo[2,3-c]pyridin-1-yl)isoquinolin-5-amine ([F]MK6240) has high affinity and selectivity for hyperphosphorylated tau and readily crosses the blood-brain barrier. This study investigated whether the early phase of [F]MK6240 can be used to provide a surrogate index of cerebral perfusion. Forty-nine subjects who were cognitively normal (CN), had mild cognitive impairment (MCI), or had Alzheimer's disease (AD) underwent paired dynamic [F]MK6240 and [C]Pittsburgh compound B (PiB) PET, as well as structural MRI to obtain anatomic information.

Kinetic evaluation and assessment of longitudinal changes in reference region and extracerebral [F]MK-6240 PET uptake.

[F]MK-6240 meningeal/extracerebral off-target binding may impact tau quantification. We examined the kinetics and longitudinal changes of extracerebral and reference regions. [F]MK-6240 PET was performed in 24 cognitively-normal and eight cognitively-impaired subjects, with arterial samples in 13 subjects.

Menopause Status Moderates Sex Differences in Tau Burden: A Framingham PET Study.

Objective: Women have a higher lifetime risk of Alzheimer's disease (AD) than men. Among cognitively normal (CN) older adults, women exhibit elevated tau positron emission tomography (PET) signal compared with men. We explored whether menopause exacerbates sex differences in tau deposition in middle-aged adults.

Associations Between Brainstem Volume and Alzheimer's Disease Pathology in Middle-Aged Individuals of the Framingham Heart Study.

The brainstem is among the first regions to accumulate Alzheimer's disease (AD)-related hyperphosphorylated tau pathology during aging. We aimed to examine associations between brainstem volume and neocortical amyloid-β or tau pathology in 271 middle-aged clinically normal individuals of the Framingham Heart Study who underwent MRI and PET imaging. Lower volume of the medulla, pons, or midbrain was associated with greater neocortical amyloid burden.

Association of cortical microstructure with amyloid-β and tau: impact on cognitive decline, neurodegeneration, and clinical progression in older adults.

Noninvasive biomarkers of early neuronal injury may help identify cognitively normal individuals at risk of developing Alzheimer's disease (AD). A recent diffusion-weighted imaging (DWI) method allows assessing cortical microstructure via cortical mean diffusivity (cMD), suggested to be more sensitive than macrostructural neurodegeneration. Here, we aimed to investigate the association of cMD with amyloid-β and tau pathology in older adults, and whether cMD predicts longitudinal cognitive decline, neurodegeneration and clinical progression.

Pathological correlates of impaired self-awareness of memory function in Alzheimer's disease.

Introduction: Impaired self-awareness of memory function, a.k.a.

Quantitative PET in the 2020s: a roadmap.

Positron emission tomography (PET) plays an increasingly important role in research and clinical applications, catalysed by remarkable technical advances and a growing appreciation of the need for reliable, sensitive biomarkers of human function in health and disease. Over the last 30 years, a large amount of the physics and engineering effort in PET has been motivated by the dominant clinical application during that period, oncology. This has led to important developments such as PET/CT, whole-body PET, 3D PET, accelerated statistical image reconstruction, and time-of-flight PET.

Nonlinear Distributional Mapping (NoDiM) for harmonization across amyloid-PET radiotracers.

Introduction: There is a growing need in clinical research domains for direct comparability between amyloid-beta (Aβ) Positron Emission Tomography (PET) measures obtained via different radiotracers and processing methodologies. Previous efforts to provide a common measurement scale fail to account for non-linearities between measurement scales that can arise from these differences. We introduce a new application of distribution mapping, based on well established statistical orthodoxy, that we call Nonlinear Distribution Mapping (NoDiM).

Neuroinflammation in Huntington's Disease: New Insights with C-PBR28 PET/MRI.

Huntington's disease is a devastating neurodegenerative genetic disorder that causes progressive motor dysfunction, emotional disturbances, and cognitive impairment. Unfortunately, there is no treatment to cure or slow the progression of the disease. Neuroinflammation is one hallmark of Huntington's disease, and modulation of neuroinflammation has been suggested as a potential target for therapeutic intervention.

PET imaging of tau protein targets: a methodology perspective.

The two neuropathological hallmarks of Alzheimer's disease (AD) are amyloid-[Formula: see text] plaques and neurofibrillary tangles of tau protein. Fifteen years ago, Positron Emission Tomography (PET) with Pittsburgh Compound B (C-PiB) enabled selective in-vivo visualization of amyloid-[Formula: see text] plaque deposits and has since provided valuable information about the role of amyloid-[Formula: see text] deposition in AD. The progression of tau deposition has been shown to be highly associated with neuronal loss, neurodegeneration, and cognitive decline.

Analytical study of the effect of the system geometry on photon sensitivity and depth of interaction of positron emission mammography.

Positron emission mammography (PEM) cameras are novel-dedicated PET systems optimized to image the breast. For these cameras it is essential to achieve an optimum trade-off between sensitivity and spatial resolution and therefore the main challenge for the novel cameras is to improve the sensitivity without degrading the spatial resolution. We carry out an analytical study of the effect of the different detector geometries on the photon sensitivity and the angle of incidence of the detected photons which is related to the DOI effect and therefore to the intrinsic spatial resolution.

Effect of MR contrast agents on quantitative accuracy of PET in combined whole-body PET/MR imaging.

Purpose: Clinical PET/MR acquisition protocols entail the use of MR contrast agents (MRCA) that could potentially affect PET quantification following MR-based attenuation correction (AC). We assessed the effect of oral and intravenous (IV) MRCA on PET quantification in PET/MR imaging.

Methods: We employed two MRCA: Lumirem (oral) and Gadovist (IV).

An assessment of the impact of incorporating time-of-flight information into clinical PET/CT imaging.

The introduction of fast scintillators with good stopping power for 511-keV photons has renewed interest in time-of-flight (TOF) PET. The ability to measure the difference between the arrival times of a pair of photons originating from positron annihilation improves the image signal-to-noise ratio (SNR). The level of improvement depends upon the extent and distribution of the positron activity and the time resolution of the PET scanner.