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Contrast-enhanced ultrasound with sub-micron sized contrast agents detects insulitis in mouse models of type1 diabetes.

ABSTRACT: In type1 diabetes (T1D) autoreactive T-cells infiltrate the islets of Langerhans, depleting insulin-secreting ?-cells (insulitis). Insulitis arises during an asymptomatic phase, prior to clinical diagnosis of T1D. Methods to diagnose insulitis and ?-cell mass changes during this asymptomatic phase are limited, precluding early therapeutic intervention. During T1D the islet microvasculature increases permeability, allowing nanoparticles to access the microenvironment. Contrast enhanced ultrasound (CEUS) uses shell-stabilized gas bubbles to provide acoustic backscatter in vasculature. Here, we report that sub-micron sized 'nanobubble' ultrasound contrast agents can be used to measure increased islet microvasculature permeability and indicate asymptomatic T1D. Through CEUS and histological analysis, pre-clinical models of T1D show accumulation of nanobubbles specifically within pancreatic islets, correlating with insulitis. Importantly, accumulation is detected early in disease progression and decreases with successful therapeutic intervention. Thus, sub-micron sized nanobubble ultrasound contrast agents provide a predicative marker for disease progression and therapeutic reversal early in asymptomatic T1D.

SUBMITTER: Ramirez DG

PROVIDER: S-EPMC7206014 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Contrast-enhanced ultrasound with sub-micron sized contrast agents detects insulitis in mouse models of type1 diabetes.

Ramirez David G DG Abenojar Eric E Hernandez Christopher C Lorberbaum David S DS Papazian Lucine A LA Passman Samantha S Pham Vinh V Exner Agata A AA Benninger Richard K P RKP

Nature communications 20200507 1

In type1 diabetes (T1D) autoreactive T-cells infiltrate the islets of Langerhans, depleting insulin-secreting β-cells (insulitis). Insulitis arises during an asymptomatic phase, prior to clinical diagnosis of T1D. Methods to diagnose insulitis and β-cell mass changes during this asymptomatic phase are limited, precluding early therapeutic intervention. During T1D the islet microvasculature increases permeability, allowing nanoparticles to access the microenvironment. Contrast enhanced ultrasound ...[more]

PMID: 32382089

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Project description:BackgroundThe aim of modern medicine is to safely classify diseases for successful therapy without invasive measures. Sonography, computed tomography (CT), and magnetic resonance imaging (MRI) are potent imaging techniques. However, without contrast medium, the informative value of the 3 native methods is limited. The advantages of sonography are: no radiation exposure or previously known physically harmful interactions with tissue, proportionate disappearance of a contrast agent risk, no (probably irreversible) contrast agent deposits, and no risk of renal insufficiency. But, is that enough to compete with of even exceed CT and MRI?SummaryIn this review, the state of the art of contrast-enhanced ultrasound (CEUS) in the abdominal cavity is presented. The remarkable diagnostic possibilities can unfortunately only be demonstrated here in a small number of impressive, typical case studies underpinned by the literature, so that, from one's own perspective, the full spectrum of CEUS can be used by oneself or initiated. Within the limits of physics, the real-time dynamics of CEUS enable conclusions to be drawn, so that with the current technology, sonography, including expansion by contrast, can be considered superior to other imaging methods. It is not uncommon for CEUS to have the value of a control and reference method.Key messagesSonography very often enables reliable diagnostics. The introduction of a contrast agent in sonography has led to a quantum leap similar to that of other imaging techniques. Already natively, the real-time representation of dynamic events leads to a certain superiority, i.e., complete observation of the inflow and outflow phases of the contrast medium and the resulting diagnostic; tissue-specific differentiation options provide a unique selling point. Further advantages of the first-choice imaging diagnostic method are: a lack of radiation exposure, repeatability of the examination at any time, local independence, a negligible allergy rate compared to the contrast agents of other methods, and a lack of kidney and thyroid exposure or excluded deposits.

Dataset Information

Contrast-enhanced ultrasound with sub-micron sized contrast agents detects insulitis in mouse models of type1 diabetes.

Publications

Contrast-enhanced ultrasound with sub-micron sized contrast agents detects insulitis in mouse models of type1 diabetes.

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