A Contrast-free Ultrasound-based Quantitative Angio Flow Imaging Technique to Assess Peripheral Arterial Disease of Lower Limb

Abstract/Summary PAD is characterized by impaired blood flow to the lower extremities, causing claudication and exercise intolerance. Up to now, assessment of PAD is mainly performed by determination of stenosis or occlusion in the large arteries and does not focus on microcirculation. Impaired arteriolar endothelial function, microvascular responsiveness to specific stimuli in patients with PAD may play a central role in disease development and progression. The impaired microvascular reactivity can be assessed by hyperemic response to contraction and cuff occlusion as well as in response to submaximal exercise. Therefore, imaging microvascular flow reactivity at various scales using methods that are safe, noninvasive, reliably quantitative, and low-cost through application of already widely available technology is critically important for early diagnosis and management of PAD. Here, we propose a novel contrast-free ultrasound pressure-based method equipped with novel quantitative metrics that involves estimation of blood flow signals in the calf muscle through processing ultrasound data frames by means of coherent ensemble selection, clutter filtering using singular value decomposition, and background noise equalization, followed by quantitative analysis of the flow variations in response to external pressure and submaximal exercise. Our vision is to complement US with additional quantitative information of microvascular flow imaging that is relevant to disease progression. Our long-term goal is to develop a new noninvasive tool for early diagnosis of PAD. A secondary gain from such an imaging method will be monitoring the disease progression and the response to interventional treatment in PAD patients. The proposed contrast-free ultrasound-based technique is named Angio Flow Reactivity Analysis (AFRA). An advantage of this technique is that it does not require the use of contrast agents to produce high-resolution images of the microvasculature flow. The project includes 2 specific aims: Specific Aim 1- Determine the efficacy of the new contrast-free US-based method, AFRA, for assessment of PAD in patient volunteers with symptoms of claudication or atypical leg syndrome and correlate the results with ABI and CTA. Specific Aim #2- Determine the efficacy of the proposed contrast-free US-based method, AFRA, for assessment of disease progression and monitoring the response to interventional treatment in patients diagnosed with PAD and correlate and the results with ABI and CTA. This proposal is the result of collaboration among several experts in the field and benefits from the world-class clinical researchers and facilities at Mayo Clinic. The overall project aims to develop a new contrast-free ultrasound tool for evaluating microvascular flow changes in the lower leg of patients at risk for PAD, a disease that leads to common disabilities, amputation, and major cardiovascular events. Successful completion of this research will open the door for a new technology for this group of patients in the clinic.