WARS2 mutations cause dopa-responsive early-onset parkinsonism and progressive myoclonus ataxia

4 Jun

Focused ultrasound-induced blood-brain barrier opening: A comparative analysis of permeability quantification based on K trans and PS

Purpose: Focused ultrasound-induced blood-brain barrier (BBB) opening is a promising method for neurotherapeutic delivery. The standard for quantifying induced BBB permeability is the $K^{\text{trans}}$ parameter, which reflects both permeability and plasma flow. The influence of plasma flow can be eliminated by estimating the PS parameter. However, this parameter has been largely unexplored in this application. This study aims to compare permeability estimates based on $K^{\text{trans}}$ and PS in focused ultrasound-induced BBB opening experiments.

Methods: We used the extended Tofts model (ETM) and the two-compartment exchange model (2CXM) to estimate $K^{\text{trans}}$ and PS parameters, respectively. Permeability estimates were compared using simulated concentration curves, simulated DCE-MRI data, and real datasets. We explored the influence of spatially-regularized model fitting on the results.

Results: For opened BBB, $K^{\text{trans}}$ was minimally influenced by plasma flow under the tested conditions. However, fitting the ETM often introduced outliers in $K^{\text{trans}}$ estimates in regions with closed BBB. The 2CXM outperformed the ETM at high signal-to-noise ratios, but its higher complexity led to lower precision at low signal-to-noise ratios. Both these issues were successfully compensated by spatially-regularized model fitting.

4 Jun

Assessing Laryngeal Neuromotor Activity from Phonation

Neurodegenerative motor disorders affect the neuromuscular system challenging daily life and normal activity. Parkinson's Disease (PD) is among the most prevalent ones, with a large impact and rising prevalence rates. Speech is most affected by PD as far as phonatory and articulatory performance is concerned. Neuromotor activity (NMA) alterations have an impact on larynx muscles responsible for vocal fold adduction and abduction, hampering phonation stability and regularity. The main muscular articulators involved in phonation control are the cricothyroid (tensor) and thyroarytenoid (relaxer) systems, regulated by two distinct direct neuromotor pathways, activated by the precentral gyrus laryngeal control areas. These articulations control the musculus vocalis, directly responsible for regular vocal fold vibration. An indirect estimation of the muscular tension produced by inverse filtering may split into two independent channels, assumed to be the tensor and relaxer neuromotor pathways such as the differential neuromotor activity (DNMA). The amplitude distributions of both DNMA channels allow comparing phonations from PD-affected persons (PDPs) and age-matched healthy control participants (HCPs) with respect to a set of reference mid-age normative participants (RSPs). The comparisons are carried out by Jensen-Shannon distributions of PDP and HCP phonations with respect to those of RSPs. A dataset of 96 phonation samples from participants balanced by gender is used to train a set of decision tree classifiers (DTCs) to distinguish PDP from HCP phonation.