Biology subjects

Sossi, V.

Publications and source records attributed to Sossi, V..

3 recordsLinked to original sources

bioRxiv2021

Lower Aβ-PET signal in white matter lesions relates to higher extracellular free water in mixed small vessel disease and Alzheimer's pathology

White matter (WM) injury is frequently observed along with dementia. Positron emission tomography with amyloid-ligands (A{beta}-PET) recently gained interest for detecting WM injury. Yet, little is understood about the origin of the altered A{beta}-PET signal in WM regions. Here, we investigated the relative contributions of diffusion MRI-based microstructural alterations, including free water and tissue-specific properties, to A{beta}-PET in WM and to cognition. We included a unique cohort of 115 participants covering the spectrum of low-to-severe white matter hyperintensity (WMH) burden and cognitively normal to dementia. We applied a bi-tensor diffusion-MRI model that differentiates between (i) the extracellular WM compartment (represented via free water), and (ii) the fiber-specific compartment (via free water-adjusted fractional anisotropy [FA]). We observed that, in regions of WMH, a decrease in A{beta}-PET related most closely to higher free water and higher WMH volume. In contrast, in normal-appearing WM, an increase in A{beta}-PET related more closely to higher cortical A{beta} (together with lower free water-adjusted FA). In relation to cognitive impairment, we observed a closer relationship with higher free water than with either free water-adjusted FA or WM PET. Our findings support free water and A{beta}-PET as markers of WM abnormalities in patients with mixed dementia, and contribute to a better understanding of processes giving rise to the WM PET signal.

neuroscience↗

bioRxiv2019

Detection of Transient Neurotransmitter Response Using Personalized Neural Networks

AO_SCPLOWBSTRACTC_SCPLOWMeasurement of stimulus-induced dopamine release and other types of transient neurotransmitter response (TNR) from dynamic PET images typically suffers from limited detection sensitivity and high false positive rates. Measurement of TNR of a voxel-level can be particularly problematic due to high image noise. In this work, we perform voxel-level TNR detection using artificial neural networks (ANN) and compare their performance to previously used standard statistical tests. Different ANN architectures were trained and tested using simulated and real human PET imaging data, obtained with the tracer [11C]raclopride (a D2 receptor antagonist). A distinguishing feature of our approach is the use of "personalized" ANNs that are designed to operate on the image from a specific subject and scan. Training of personalized ANNs was performed using simulated images that have been matched with the acquired image in terms of the signal and noise. In our tests of TNR detection performance, the F-test of the linear parametric neurotransmitter PET (lp-ntPET) model fit residuals was used as the reference method. For a moderate TNR magnitude, the areas under the receiver operating characteristic curves in simulated tests were 0.64 for the F-test and 0.77-0.79 for the best ANNs. At a fixed false positive rate of 0.01, the true positive rates were 0.6 for the F-test and 0.8-0.9 for the ANNs. When applied to a real image, the ANNs identified a TNR cluster missed by the F-test. The newly found cluster was verified to contain TNR by direct lp-ntPET model fitting. These results demonstrate that personalized ANNs may offer a greater detection sensitivity of dopamine release and other types of TNR compared to previously used methods.

neuroscience↗

bioRxiv2019

Brain morphology predicts long-term placebo response in multiple sclerosis patients

Although significant insights have been gained into the neural mechanisms of acute placebo responses, less is known about the mechanisms of longer-term placebo responses, such as those seen in clinical trials, or the interactions between these mechanisms and brain disease. We examined neuropathological and morphological brain correlates of placebo responses in a randomized clinical trial of a controversial endovascular treatment ("liberation therapy") for multiple sclerosis. Patients were randomized to receive either balloon or sham extracranial venoplasty and followed for 48 weeks. The trial did not support therapeutic efficacy of venoplasty, but a subset of both venoplasty- and sham-treated patients reported an improvement in health-related quality of life that peaked at 12 weeks following treatment, suggesting a placebo response. Placebo responders had higher lesion activity than placebo non-responders. Although placebo responders did not differ from non-responders in terms of total normalized brain volume, regional grey or white matter volume or cortical thickness, graph theoretical analysis of cortical thickness covariance showed that placebo non-responders had a more homogenous cortical thickness topology with a more small-world-like architecture. In placebo non-responders, lesion load inversely predicted cortical thickness in primary somatosensory and motor areas, association areas, precuneus and insula, primarily in the right hemisphere. In placebo responders, lesion load was unrelated to cortical thickness. The neuropathological process in MS may result in a cortical configuration that is less suited to functional integration and less capable of generating a sustained placebo response.

neuroscience↗