Dynamic contrast-enhanced ultrasound for assessment of therapy effects on skeletal muscle microcirculation in peripheral arterial disease: pilot study.

OBJECTIVE: To assess with dynamic contrast-enhanced ultrasound (CEUS) and transient arterial occlusion whether the muscular micro-perfusion in patients with peripheral arterial disease (PAD) is improved after angioplasty or surgery. MATERIALS AND METHODS: This study had local institutional review board approval. Written informed consent was obtained from all 20 patients with PAD, Fontaine stage IIb (mean age, 64 years), who participated in the study. Low-MI CEUS (7MHz; MI, 0.28) was applied to the mainly affected lower leg after start of a continuous automatic intravenous injection of 4.8mL SonoVue(®). Muscle-perfusion was monitored by CEUS before, during, and after provocation by arterial occlusion at the thigh level lasting for 60s. CEUS examination was performed a second time within 14 days after angioplasty (n=15), thrombendarterectomy (n=2), angioplasty and thrombendarterectomy (n=1), or bypass (n=2). Clinical amelioration was re-evaluated within 6 months after the intervention using a 4-point scale. RESULTS: Ankle-brachial-index (ABI) increased from 0.8±0.2 to 0.9±0.3 after treatment (p=0.01). Time to maximum CEUS signal (tmax) shortened from 26±14s to 14±4s (p=0.004). The slope to maximum after transient occlusion (m2) changed to steeper values (6.4±5.8∼mL/s versus 10.2±5.0∼mL/s; p=0.04). Shortened tmax predicted improvement in the patients' intermittent leg pain and therefore successful therapy outcome. CONCLUSION: Dynamic CEUS with transient arterial occlusion can visualize the treatment-induced improvement of muscular micro-perfusion in patients with PAD.

Dynamic contrast-enhanced ultrasound and transient arterial occlusion for quantification of arterial perfusion reserve in peripheral arterial disease.

OBJECTIVE: To quantify muscular micro-perfusion and arterial perfusion reserve in peripheral arterial disease (PAD) with dynamic contrast-enhanced ultrasound (CEUS) and transient arterial occlusion. MATERIALS AND METHODS: This study had local institutional review board approval and written informed consent was obtained from all subjects. We examined the dominant lower leg of 40 PAD Fontaine stage IIb patients (mean age, 65 years) and 40 healthy volunteers (mean age, 54 years) with CEUS (7 MHz; MI, 0.28) during continuous intravenous infusion of 4.8 mL microbubbles. Transient arterial occlusion at mid-thigh level simulated physical exercise. With time-CEUS-intensity curves obtained from regions of interest within calf muscles, we derived the maximum CEUS signal after occlusion (max) and its time (tmax), slope to maximum (m), vascular response after occlusion (AUC(post)), and analysed accuracy, receiver operating characteristic (ROC) curves, and correlations with ankle-brachial index (ABI) and walking distance. RESULTS: All parameters differed in PAD and volunteers (p<0.014). In PAD, tmax was delayed (31.2±13.6 vs. 16.7±8.5 s, p<0.0001) and negatively correlated with ankle-brachial-index (r=-0.65). m was decreased in PAD (4.3±4.6 mL/s vs. 13.1±8.4 mL/s, p<0.0001) and had highest diagnostic accuracy (sensitivity/specificity, 75%/93%) for detection of diminished muscular micro-perfusion in PAD (cut-off value, m<5∼mL/s). Discriminant analysis and ROC curves revealed m, and AUC(post) as optimal parameter combination for diagnosing PAD and therefore impaired arterial perfusion reserve. CONCLUSIONS: Dynamic CEUS with transient arterial occlusion quantifies muscular micro-perfusion and arterial perfusion reserve. The technique is accurate to diagnose PAD.

[Contrast-enhanced ultrasound of skeletal muscle]. / Kontrastverstärkter Ultraschall der Skelettmuskulatur.

Functional imaging can increase the role of imaging in muscular diseases, as alterations of muscle morphology alone are non-specific for a particular disease. A good example for these functional imaging techniques is to use contrast-enhanced ultrasound (CEUS) to visualize and quantify in vivo (patho-) physiological information about the skeletal muscle microcirculation. Perfusion, i.e. the blood flow per tissue unit including capillary flow, is an important functional parameter. Pathological changes of skeletal muscle perfusion can be found in various clinical conditions, such as degenerative or inflammatory myopathy or peripheral arterial disease (PAD). This article reviews the theoretical basics of functional radiological techniques for assessing skeletal muscle perfusion and focuses on applications of microvascular imaging by CEUS which has improved the diagnosis of these muscular disorders. For evaluation of myositis, CEUS is more efficient in the diagnostic work-up than routine b-mode ultrasound because CEUS can detect inflammation-induced muscular hyperperfusion in acute myositis. This has already been demonstrated by high-mechanical index techniques using a first generation ultrasound contrast agent. Low-mechanical index CEUS techniques that require the use of a second generation contrast agent allow real-time quantification of muscular microcirculation at rest and during exercise. Using this CEUS method, the influence of different exercise intensities on the microcirculation of the exercising muscle becomes detectable. Moreover, the arterial perfusion reserve in PAD can be adequately examined using low-mechanical index CEUS. Initial findings have shown that the arterial perfusion reserve in patients suffering from PAD is reduced in comparison to healthy volunteers. In conclusion, modern CEUS techniques can offer deeper insights in muscular (patho-) physiology than just illustrating unspecific myopathic manifestations using conventional diagnostic imaging, such as edematous or lipomatous changes, hypertrophy or atrophy.