Super-Resolution Ultrasound Imaging of Skeletal Muscle Microvascular Dysfunction in an Animal Model of Type 2 Diabetes

Objectives: To evaluate the use of super-resolution ultrasound (SR-US) imaging for quantifying microvascular changes in skeletal muscle using a mouse model of type 2 diabetes. Methods: Study groups were young, standard chow–fed male C57BL/6J mice (lean group) and high fat diet–fed older mice (obese group). After an overnight fast, dynamic contrast-enhanced US imaging was performed on the proximal hind limb adductor muscle group for 10 minutes at baseline and again at 1 and 2 hours during administration of a hyperinsulinemic-euglycemic clamp. Dynamic contrast-enhanced US images were collected on a clinical US scanner (Acuson Sequoia 512; Siemens Healthcare, Mountain View, CA) equipped with a 15L8 linear array transducer. Dynamic contrast-enhanced US images were processed with a spatiotemporal filter to remove tissue clutter. Individual microbubbles were localized and counted to create an SR-US image. A frame-by-frame analysis of the microbubble count was generated (ie, time-microbubble count curve [TMC]) to estimate tissue perfusion and microvascular blood flow. The conventional time-intensity curve (TIC) was also generated for comparison. Results: In vivo SR-US imaging could delineate microvascular structures in the mouse hind limb. Compared with lean animals, insulin-induced microvascular recruitment was attenuated in the obese group. The SR-US-based TMC analysis revealed differences between lean and obese animal data for select microvascular parameters (P <.04), which was not true for TIC-based measurements. Whereas the TMC and TIC microvascular parameters yielded similar temporal trends, there was less variance associated with the TMC-derived values. Conclusions: Super-resolution US imaging is a new modality for measuring the microvascular properties of skeletal muscle and dysfunction from type 2 diabetes.