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.