Contrast-Enhanced Ultrasound Assessment of Impaired Adipose Tissue and Muscle Perfusion in Insulin-Resistant Mice

Belcik, J. Todd; Davidson, Brian P.; Foster, Ted; Qi, Yue; Zhao, Yan; Peters, Dawn; Lindner, Jonathan R.

doi:10.1161/circimaging.114.002684

Cited by 26 publications

(19 citation statements)

References 36 publications

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“…First, the length of training may not have been long enough to cause sufficient fat loss to see improvements in adipose tissue MBV or MBF at rest or during the OGC. This is particularly important given that the degree of obesity is negatively associated with adipose MBV and MBF (2,15). Second, this type of exercise training (RT rather than aerobic exercise) may not be sufficient to sensitize the microcirculation to respond to the OGC.…”

Section: Discussionmentioning

confidence: 99%

Are the metabolic benefits of resistance training in type 2 diabetes linked to improvements in adipose tissue microvascular blood flow?

Russell

Remash

et al. 2018

American Journal of Physiology-Endocrinology and Metabolism

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The microcirculation in adipose tissue is markedly impaired in type 2 diabetes (T2D). Resistance training (RT) often increases muscle mass and promotes a favorable metabolic profile in people with T2D, even in the absence of fat loss. Whether the metabolic benefits of RT in T2D are linked to improvements in adipose tissue microvascular blood flow is unknown. Eighteen sedentary people with T2D (7 women/11 men, 52 ± 7 yr) completed 6 wk of RT. Before and after RT, overnight-fasted participants had blood sampled for clinical chemistries (glucose, insulin, lipids, HbA1c, and proinflammatory markers) and underwent an oral glucose challenge (OGC; 50 g glucose × 2 h) and a DEXA scan to assess body composition. Adipose tissue microvascular blood volume and flow were assessed at rest and 1 h post-OGC using contrast-enhanced ultrasound. RT significantly reduced fasting blood glucose ( P = 0.006), HbA1c ( P = 0.007), 2-h glucose area under the time curve post-OGC ( P = 0.014), and homeostatic model assessment of insulin resistance ( P = 0.005). This was accompanied by a small reduction in total body fat ( P = 0.002), trunk fat ( P = 0.023), and fasting triglyceride levels ( P = 0.029). Lean mass ( P = 0.003), circulating TNF-α ( P = 0.006), and soluble VCAM-1 ( P < 0.001) increased post-RT. There were no significant changes in adipose tissue microvascular blood volume or flow following RT; however those who did have a higher baseline microvascular blood flow post-RT also had lower fasting triglyceride levels ( r = −0.476, P = 0.045). The anthropometric, glycemic, and insulin-sensitizing benefits of 6 wk of RT in people with T2D are not associated with an improvement in adipose tissue microvascular responses; however, there may be an adipose tissue microvascular-linked benefit to fasting triglyceride levels.

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Section: Discussionmentioning

confidence: 99%

Are the metabolic benefits of resistance training in type 2 diabetes linked to improvements in adipose tissue microvascular blood flow?

Russell

Remash

et al. 2018

American Journal of Physiology-Endocrinology and Metabolism

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“…Signaling in response to insulin in endothelial cells also promotes the movement of insulin from the circulation to the underlying muscle cells . Studies in both humans and animal models indicate that attenuations in the skeletal muscle microvascular response to insulin play a critical role in type 2 diabetes and obesity‐induced insulin resistance . However, the basis for impaired skeletal muscle microvascular function and how it contributes to type 2 diabetes remains enigmatic in various high‐risk patient populations.…”

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confidence: 99%

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

Ghosh

Peng

Brown

et al. 2019

J of Ultrasound Medicine

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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.

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“…Then, the 309 conditional probability becomes: 310 (6) where D is the scaling constant of the dynamic range, ρ is the correlation coefficient and  = 311 n1 /n2 312 The registration and correction were firstly conducted on the simultaneously acquired B-mode 313 sequence and then transferred to CEUS image sequence.314 315 Destruction and Replenishment (DR) analysis 316The in vivo flow quantification was calculated using destruction replenishment time-intensity 317 data(Lindner, et al 2008, Wei, et al 1998. A frame obtained 0.08 second after destruction is 318 used as the background and is subtracted from subsequent frames to eliminate signal from non-319 capillary vessels(Belcik, et al 2015). The replenishment curve was fitted with a mono 320 exponential function, = (1 − − ), where y is video intensity, A is plateau intensity and  321 is the rate constant using a non-linear least squares fitting algorithm in MATLAB.…”

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confidence: 99%

A Temporal and Spatial Analysis Approach to Automated Segmentation of Microbubble Signals in Contrast-Enhanced Ultrasound Images: Application to Quantification of Active Vascular Density in Human Lower Limbs

Cheung

Williams

Christensen-Jeffries

et al. 2017

Ultrasound in Medicine & Biology

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Contrast-enhanced ultrasound (CEUS) using microbubble contrast agents has shown great promise in visualising and quantifying active vascular density. Most existing approaches for vascular density quantification using CEUS are calculated based on image intensity and are susceptible to confounding factors and imaging artefact. Poor reproducibility is a key challenge to clinical translation. In this study, a new automated temporal and spatial signal analysis approach is developed for reproducible microbubble segmentation and quantification of contrast enhancement in human lower limbs. The approach is evaluated in vitro on phantoms and in vivo in lower limbs of healthy volunteers before and after physical exercise. In this approach, vascular density is quantified based on the relative areas microbubbles occupy instead of their image intensity. Temporal features of the CEUS image sequences are used to identify pixels that contain microbubble signals. A microbubble track density (MTD) measure, the ratio of the segmented microbubble area to the whole tissue area, is calculated as a surrogate for active capillary density. In vitro results reveal a good correlation (r = 0.89) between the calculated MTD measure and the known bubble concentration. For in vivo results, a significant increase (129% in average) in the MTD measure is found in lower limbs of healthy volunteers after exercise, with excellent repeatability over a series of days (intra-class correlation coefficient = 0.96). This compares to the existing state-of-the-art approach of destruction and replenishment analysis on the same patients (intra-class correlation coefficient ≤0.78). The proposed new approach shows great potential as an accurate and highly reproducible clinical tool for quantification of active vascular density.

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Contrast-Enhanced Ultrasound Assessment of Impaired Adipose Tissue and Muscle Perfusion in Insulin-Resistant Mice

Cited by 26 publications

References 36 publications

Are the metabolic benefits of resistance training in type 2 diabetes linked to improvements in adipose tissue microvascular blood flow?

Are the metabolic benefits of resistance training in type 2 diabetes linked to improvements in adipose tissue microvascular blood flow?

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

A Temporal and Spatial Analysis Approach to Automated Segmentation of Microbubble Signals in Contrast-Enhanced Ultrasound Images: Application to Quantification of Active Vascular Density in Human Lower Limbs

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