Preclinical ultrasound for development translatable model of metabolic syndrome in small animals

Abstract

Objectives Diagnostic ultrasound (US) using general US imaging devices can be effectively used for preclinical studies in small animals providing dynamic life-time control [1], furthermore, can enhance drug delivery and therapeutic effects with visual treatment monitoring (theranostic). The Aim was to develop model of metabolic syndrome in small animals using general US machines for longitudinal in vivo observation and screening large numbers of cases for facilitating further translation. Methods The modeling of metabolic syndrome performed compliance with the ethical standards and includes conducting an experiment on laboratory animals (mice, rats, murine) with the introduction of high calorie diet or industrial fat-enriched diet; and further US monitoring using 5–20 MHz probes of diagnostic US machines in grey scale, Doppler, sonoelastography, M-mode detecting tissue movement, US-guided interventions, injection US contrast agents: 1) for precise diagnosis transabdominal US detecting signs of metabolic syndrome via detailed imaging of internal organs: liver size, echogeneicity, stiffness, kidneys structure, Doppler measuring resistance index (RI) on segmental renal arteries, spleen length, muscle thickness at the midfemoral level, assessment of visceral vessels, systemic hemodynamics, etc.; 2) for screening all involved animals we measured the visceral fat thickness (threshold considered as 1.5 mm in mice) on sagittal probe position and collected records of panoramic abdominal scans (in sagittal and transverse probe positions) and measured the largest longitudinal liver size (via subcostal approach). Weight, body size, laboratory indices (cholesterol, uric acid, glucose, etc.), microbiome, genetic markers were also determined. After sacrificing we evaluated studied organs. Results The model was successfully applied to study effects of new drugs: probiotic strains on high calorie-induced obesity model in BALB/c during 21 days [2] and prebiotic on high-calorie diet-induced obesity in rats [3]. US detected development metabolic syndrome, endogenous intoxication syndrome, visceral obesity and liver and kidney dysfunction in mouse and rats. Ultrasound data showed visceral obesity, injury of the liver and organs in all experimental animals. We revealed nephropathy signs (thinning, increasing echogenicity of kidney parenchyma, detecting increasing RI in renal arteries (over 0.7) was feasible in rats. Studies using the models demonstrated efficacy of studied strains, substances improving parameters during experiment. All observed changes were confirmed post mortem. Conclusions The method of modeling is reliable, allows to monitor metabolic syndrome signs with high translation potential reflecting development disease in humans.