Biology subjects

Metzler-baddeley, C.

Publications and source records attributed to Metzler-baddeley, C..

3 recordsLinked to original sources

bioRxiv2024

Imaging brain vascular function in Cystic Fibrosis: an MRI study of cerebral blood flow and brain oxygenation

Cystic fibrosis (CF) is a progressive inherited disorder that primarily affects the lungs. With recent breakthroughs in effective treatments for CF that increase life-expectancy, a higher prevalence of age-related comorbidities have been reported including cardiovascular disease, stroke and cognitive decline. Despite the known relationship between cardiovascular health and cerebrovascular function, very little is known about brain blood flow and oxygen metabolism in patients with CF (PwCF). In 14 PwCF and 56 healthy age / sex matched controls, we used pseudo-continuous arterial spin labelling (pCASL) to quantify cerebral perfusion in grey-matter and T2-Relaxation-Under-Spin-Tagging (TRUST) to estimate global oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen consumption (CMRO2). Compared to healthy controls, PwCF showed elevated CMRO2 (p = 0.015). There were no significant between-group differences in grey-matter CBF (p = 0.342), or whole brain OEF (p = 0.091). However, regional analysis showed certain areas with higher CBF in PwCF (p < .05, FDR). This is the first study to characterise cerebrovascular function and brain oxygen metabolism in PwCF. Our findings highlight the need for early cardiovascular monitoring procedures to help maintain cerebrovascular function and combat accelerated aging effects in the brains of PwCF.

neuroscience↗

bioRxiv2021

Multi-compartment analysis of the complex gradient-echo signal quantifies myelin breakdown in premanifest Huntington's disease

White matter (WM) alterations have been identified as a relevant pathological feature of Huntingtons disease (HD). Increasing evidence suggests that WM changes in this disorder are due to alterations in myelin-associated biological processes. Multi-compartmental analysis of the complex gradient-echo MRI signal evolution in WM has been shown to quantify myelin in vivo, therefore pointing to the potential of this technique for the study of WM myelin changes in health and disease. This study first characterized the reproducibility of metrics derived from the complex multi-echo gradient-recalled echo (mGRE) signal across the corpus callosum in healthy participants, finding highest reproducibility in the posterior callosal segment. Subsequently, the same analysis pipeline was applied in this callosal region in a sample of premanifest HD patients (n = 19) and age, sex and education matched healthy controls (n = 21). In particular, we focused on two myelin-associated derivatives: i. the myelin water signal fraction (fm), a parameter dependent on myelin content; and ii. the difference in frequency between myelin and intra-axonal water pools ({Delta}{omega}), a parameter dependent on the ratio between the inner and the outer axonal radii. fm was found to be lower in HD patients ({beta} = -0.13, p = 0.03), while {Delta}{omega} did not show a group effect. Performance in tests of working memory, executive function, social cognition and movement was also assessed, and a greater age-related decline in executive function was detected in HD patients ({beta} = -0.06, p = 0.006), replicating previous evidence of executive dysfunction in HD. Finally, the correlation between fm, executive function, and proximity to disease onset was explored in patients, and a positive correlation between executive function and fm was detected (r = 0.542; p = 0.02). This study emphasises the potential of complex mGRE signal analysis for aiding understanding of HD pathogenesis and progression. Moreover, expanding on evidence from pathology and animal studies, it provides novel in vivo evidence supporting myelin breakdown as an early feature of HD.

neuroscience↗

bioRxiv2019

Drumming motor sequence training induces myelin remodelling in Huntington's disease: a longitudinal diffusion MRI and quantitative magnetization transfer study

1.BackgroundImpaired myelination may contribute to Huntingtons disease (HD) pathogenesis. This study assessed differences in white matter (WM) microstructure between HD patients and controls, and tested whether drumming training stimulates WM remodelling in HD. Furthermore, it examined whether training-induced microstructural changes are related to improvements in motor and cognitive function. MethodsParticipants undertook two months of drumming exercises. Working memory and executive function were assessed before and after training. Changes in WM microstructure were investigated with diffusion tensor magnetic resonance imaging (DT-MRI)-based metrics, the restricted diffusion signal fraction (Fr) from the composite hindered and restricted model of diffusion (CHARMED) and the macromolecular proton fraction (MPF) from quantitative magnetization transfer (qMT) imaging. WM pathways linking the putamen and the supplementary motor area (SMA-Putamen), and three segments of the corpus callosum (CCI, CCII, CCIII) were studied using deterministic tractography. Baseline MPF differences between patients and controls were assessed with tract-based spatial statistics (TBSS). ResultsMPF was reduced in HD patients compared to controls in the mid-section of the CC in HD subjects at baseline, while a significantly greater change in MPF was detected in HD patients relative to controls in the CCII, CCIII, and the right SMA-putamen post-training. Further, although patients improved their drumming and executive function performance, such improvements did not correlate with microstructural changes. ConclusionsIncreased MPF suggests training-induced myelin changes in HD. Tailored behavioural stimulation may lead to neural benefits in early HD that could be exploited for delaying disease progression.

neuroscience↗