Phan, T. T. | Search bioRxiv

bioRxiv2025

MRS4Brain: a processing toolbox for preclinical MR spectroscopy and spectroscopic imaging data

ObjectivesMagnetic resonance spectroscopy is a non-invasive technique for probing metabolism and underpins advanced methods such as magnetic resonance spectroscopic imaging (MRSI) and diffusion-weighted spectroscopy (DWS). MRSI enables spatial mapping of metabolite distributions, offering insights into regional metabolic heterogeneity that single-voxel spectroscopy (SVS) cannot capture. However, MRSI produces large multidimensional datasets and requires complex processing pipelines, limiting reproducibility and accessibility. While human studies benefit from advanced processing tools, similar developments in preclinical research remain scarce, highlighting a demand for practical tools accessible to non-experts. MethodsTo address this need, we introduce the MRS4Brain Toolbox, a freely available MATLAB-based platform for preclinical spectroscopy, including MRSI, SVS, and DWS. ResultsThe toolbox integrates reconstruction, preprocessing, quantification, quality control, brain segmentation automatically overlaid on metabolite maps, modeling, and statistical analysis into unified workflows accessible via a graphical interface. ConclusionBy streamlining data processing and reducing technical barriers, MRS4Brain Toolbox promotes reproducibility, harmonization, and broader adoption of advanced spectroscopic techniques in preclinical studies, ultimately facilitating translational research.

neuroscience↗

bioRxiv2025

Effects of Sodium Glucose Co-Transporter Inhibitors on Work in Human Hypertrophic Cardiomyopathy Living Myocardial Slices

BackgroundDisease modifying therapies for hypertrophic cardiomyopathy (HCM) remain a prevailing unmet need. Human-based experimental platforms capable of controlled manipulation of preload and afterload can distinguish direct myocardial and systemic effects and facilitate development of targeted cardiac therapeutics. Sodium glucose cotransporter inhibitors (SGLTi) may directly affect cardiac contractility, potentially related to increased ketone availability. These effects have not been adequately studied in human HCM myocardium under defined loading conditions. AimsWe sought to establish human living myocardial slices (LMS) as a platform to interrogate load-dependent myocardial mechanics in HCM and to quantify the acute effects of metabolic and pharmacologic interventions--including SGLTi--on myocardial work under physiologic loading conditions. MethodsHuman myocardial tissue was procured from non-failing donor hearts or individuals with HCM undergoing septal myectomy. Freshly prepared human LMS were mechanically tested to generate biomimetic work loops across a range of physiologic preloads and afterloads in either glucose-only fuel or glucose supplemented with ketone. Following baseline measurements, slices were loaded with drug (isoproterenol, mavacamten, sotagliflozin, or empagliflozin) or vehicle (DMSO) and work loop analysis was repeated, allowing each slice to serve as its own control. Mixed effects linear regression models incorporating random effects for heart and slice and fixed effects for clinical characteristics evaluated determinants of myocardial work and drug response across loading conditions. ResultsA total of 120 LMS from 32 individuals (16 non-failing and 16 HCM) were analyzed. At baseline, myocardial work was positively associated with younger age, hypertension, and ejection fraction. Ketone supplementation augmented work and work-strain slope particularly in HCM LMS at high afterloads. We validated our drug testing methodology by demonstrating increased work with known positive inotrope isoproterenol, decreased work with negative inotrope mavacamtem most pronounced in HCM LMS, and a null effect of DMSO. Acute exposure to SGLTi sotagliflozin and empagliflozin directly reduced myocardial work, with increased potency of sotagliflozin at high afterloads. ConclusionsOur LMS platform enables assessment of myocardial mechanics across controlled loading conditions and is an ideal platform to rigorously phenotype human myocardial tissue and interrogate direct effects of pharmacologic intervention. We demonstrate that SGLTi and ketones have distinct and discordant effects on human myocardial contractility.

physiology↗