Detecting Changes in Tissue Perfusion With Hyperspectral Imaging and Thermal Imaging Following Endovascular Treatment for Peripheral Arterial Disease.

PURPOSE: Hyperspectral imaging (HSI) and thermal imaging allow contact-free tissue perfusion measurements and may help determine the effect of endovascular treatment (EVT) in patients with peripheral arterial disease. This study aimed to detect changes in perfusion with HSI and thermal imaging peri-procedurally and determine whether these changes can identify limbs that show clinical improvement after 6 weeks. METHODS: Patients with Rutherford class 2-6 scheduled for EVT were included prospectively. Hyperspectral imaging and thermal imaging were performed directly before and after EVT. Images were taken from the lateral side of the calves and plantar side of the feet. Concentrations of (de)oxyhemoglobin, oxygen saturation, and skin temperature were recorded. Angiographic results were determined on completion angiogram. Clinical improvement 6 weeks after EVT was defined as a decrease ≥ one Rutherford class. Peri-procedural changes in perfusion parameters were compared between limbs with and without good angiographic results or clinical improvement. To identify limbs with clinical improvement, receiver operating characteristic (ROC) curves were used to determine cutoff values for change in HSI. RESULTS: Included were 23 patients with 29 treated limbs. Change in HSI values and temperature was not significantly different between limbs with good and poor angiographic results. Change in peri-procedural deoxyhemoglobin, determined by HSI, at the calves and feet was significantly different between limbs with and without clinical improvement at 6 week follow-up (p=0.027 and p=0.017, respectively). The ROC curve for change in deoxyhemoglobin at the calves showed a cutoff value of ≤1.0, and ≤-0.5 at the feet, which were discriminative for clinical improvement (sensitivity 77%; specificity 75% and sensitivity 62%; specificity 88%, respectively). CONCLUSIONS: HSI can detect changes in perfusion at the calves after EVT in patients with Rutherford class 2-6. Peri-procedural deoxyhemoglobin changes at the calves and feet are significantly different between limbs with and without clinical improvement. Decrease in deoxyhemoglobin directly after EVT may identify limbs that show clinical improvement 6 weeks after EVT.

Determination of Changes in Tissue Perfusion at Home with Hyperspectral and Thermal Imaging in the First Six Weeks after Endovascular Therapy in Patients with Peripheral Arterial Disease.

The aims of this study were to assess changes in tissue perfusion up to 6 weeks after endovascular therapy (EVT), in hospital and at home, and to determine differences in tissue perfusion between patients with and without clinical improvement or good angiographic result. This single-center prospective cohort study included patients undergoing EVT for Rutherford stages two to six. Hyperspectral and thermal imaging were performed at the dorsal and plantar sides of the foot. These measurements consisted of a baseline measurement pre-EVT, and six follow-up measurements obtained at 1 and 4 h and 6 weeks in hospital, and 1 day, 7 days, and 14 days at home. Clinical improvement was defined as a decrease of one or more Rutherford class or decrease in the wound surface area and a good angiographic result was accomplished when a Transatlantic Inter-Society Consensus for the Management of PAD II C or D lesion was treated and uninterrupted flow continued in at least one below-the-knee artery in continuation with the inframalleolar arteries. The study included 34 patients with 41 treated limbs. Deoxyhemoglobin values were lower 1 h post-EVT compared with baseline and increased over time up to 6 weeks post-EVT. Significant differences in deoxyhemoglobin levels at 7 and 14 days post-EVT were determined between patients with and without clinical or angiographic success. This prospective pilot study shows the feasibility of hyperspectral imaging and thermal imaging post-EVT at home, which may decrease the need for hospital visits.

Laser Doppler Flowmetry Combined with Spectroscopy to Determine Peripheral Tissue Perfusion and Oxygen Saturation: A Pilot Study in Healthy Volunteers and Patients with Peripheral Arterial Disease.

BACKGROUND: In this study, we assessed the ability of the EPOS system (Perimed AB, Järfälla, Stockholm, Sweden) to detect differences in tissue perfusion between healthy volunteers and patients with peripheral arterial disease (PAD) with different severity of disease. METHODS: This single-center prospective pilot study included 10 healthy volunteers and 20 patients with PAD scheduled for endovascular therapy (EVT). EPOS measurements were performed at rest at 32 °C and 44 °C, followed by transcutaneous oxygen pressure (TcPo2) measurements. The measurements were performed on the dorsal and medial side of the foot, as well as the lateral side of the calf. EPOS parameters included hemoglobin oxygen saturation (HbSo2) and speed-resolved red blood cell (RBC) perfusion. RESULTS: HbSo2 at 44 °C was significantly different between the three groups for all measurement locations. The overall speed-resolved RBC perfusion at 44 °C was statistically significant between the groups on the dorsal and medial side of the foot but not on the calf. TcPo2 values were not significantly different between the three groups. CONCLUSIONS: This study demonstrates that the EPOS system can depict differences in tissue perfusion between healthy volunteers, patients with Fontaine class IIb PAD, and those with Fontaine class III or IV PAD but only after heating to 44 °C.

Reliability assessment of hyperspectral imaging with the HyperView™ system for lower extremity superficial tissue oxygenation in young healthy volunteers.

PURPOSE: Hyperspectral imaging (HSI) is a noninvasive spectroscopy technique for determining superficial tissue oxygenation. The HyperView™ system is a hand-held camera that enables perfusion image acquisition. The evaluation of superficial tissue oxygenation is warranted in the evaluation of patients with peripheral arterial disease. The aim was to determine the reliability of repeated HSI measurements. METHODS: In this prospective cohort study, HSI was performed on 50 healthy volunteers with a mean age of 26.4 ± 2.5 years, at the lower extremity. Two independent observers performed HSI during two subsequent measurement sessions. Short term test-retest reliability and intra- and inter-observer reliability were determined, and generalizability and decision studies were performed. Transcutaneous oxygen pressure (TcPO2) measurements were also performed. RESULTS: The short term test-retest reliability was good for the HSI values determined at the lower extremity, ranging from 0.72 to 0.90. Intra- and inter-observer reliability determined at different days were poor to moderate for both HSI (0.24 to 0.71 and 0.30 to 0.58, respectively) and TcPO2 (0.54 and 0.56, and 0.51 and 0.31, respectively). Reliability can be increased to >0.75 by averaging two measurements on different days. CONCLUSION: This study showed good short term test-retest reliability for HSI measurements, however low intra- and inter-observer reliability was observed for tissue oxygenation measurements with both HSI and TcPO2 performed at separate days in young healthy volunteers. Reliability of HSI can be improved when determined as a mean of two measurements taken on different days.

A Systematic Review and Critical Appraisal of Peri-Procedural Tissue Perfusion Techniques and their Clinical Value in Patients with Peripheral Arterial Disease.

OBJECTIVE: Many techniques have been introduced to enable quantification of tissue perfusion in patients with peripheral arterial disease (PAD). Currently, none of these techniques is widely used to analyse real time tissue perfusion changes during endovascular or surgical revascularisation procedures. The aim of this systematic review was to provide an up to date overview of the peri-procedural applicability of currently available techniques, diagnostic accuracy of assessing tissue perfusion and the relationship with clinical outcomes. DATA SOURCES: MEDLINE, Embase, CINAHL, and the Cochrane Central Register of Controlled Trials. REVIEW METHODS: This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic review and Meta-Analysis (PRISMA) guidelines. Four electronic databases were searched up to 31 12 2020 for eligible articles: MEDLINE, Embase, CINAHL and the Cochrane Central Register of Controlled Trials. Eligible articles describing a perfusion measurement technique, used in a peri-procedural setting before and within 24 hours after the revascularisation procedure, with the aim of determining the effect of intervention in patients with PAD, were assessed for inclusion. The QUADAS-2 tool was used to assess the risk of bias and applicability of the studies. RESULTS: An overview of 10 techniques found in 26 eligible articles focused on study protocols, research goals, and clinical outcomes is provided. Non-invasive techniques included laser speckle contrast imaging, micro-lightguide spectrophotometry, magnetic resonance imaging perfusion, near infrared spectroscopy, skin perfusion pressure, and plantar thermography. Invasive techniques included two dimensional perfusion angiography, contrast enhanced ultrasound, computed tomography perfusion imaging, and indocyanine green angiography. The results of the 26 eligible studies, which were mostly of poor quality according to QUADAS-2, were without exception, not sufficient to substantiate implementation in daily clinical practice. CONCLUSION: This systematic review provides an overview of 10 tissue perfusion assessment techniques for patients with PAD. It seems too early to appoint one of them as a reference standard. The scope of future research in this domain should therefore focus on clinical accuracy, reliability, and validation of the techniques.

The Impact of Lower Extremity Skeletal Muscle Atrophy and Myosteatosis on Revascularization Outcomes in Patients with Peripheral Arterial Disease.

BACKGROUND: This study investigated whether lower extremity muscle atrophy and myosteatosis in patients with peripheral arterial disease (PAD) are correlated to postoperative outcomes, such as reintervention or amputation-free survival. METHODS: In this single-center retrospective cohort study of 462 patients treated for peripheral arterial disease scheduled for intervention, muscle mass and the presence of fattening of the lower extremity muscles were measured semiautomatically in a single computed tomography slice of the treated leg. Binary logistic regression models and Cox proportional hazards models were used to determine the effect of muscle atrophy and myosteatosis on reintervention and amputation. RESULTS: Muscle atrophy and myosteatosis increased in PAD patients with Fontaine class IV compared with Fontaine class IIa. In PAD patients with muscle atrophy or myosteatosis, no association was found with the reintervention rate or reintervention-free survival, but an association was found with amputation-free survival, even after adjustment for patient-related, disease-severity, and comorbidities-related factors. CONCLUSION: Muscle atrophy and mysosteatosis increased in PAD patients with increasing disease severity. Lower extremity muscle atrophy and myosteatosis are associated with amputation rate and amputation-free survival in PAD patients. No association with reintervention rate or reintervention-free survival was found. Muscle atrophy and myosteatosis may serve as additional risk factors in decision making in the often frail vascular patient.

Hyperspectral imaging for noninvasive tissue perfusion measurements of the lower leg: review of literature and introduction of a standardized measurement protocol with a portable system.

INTRODUCTION: Hyperspectral imaging (HSI) is a noninvasive technique for transcutaneous measurements of tissue perfusion. This study (1) provides a review of the current literature on HSI for tissue perfusion measurements of the lower leg and (2) introduces a standardized measurement protocol for HSI measurements with a portable system. EVIDENCE ACQUISITION: A literature search was performed for studies on tissue perfusion measurements with HSI in the lower extremity. A standardized protocol was developed to perform HSI measurements in 43 healthy volunteers at the plantar side of the foot and at the lateral side of the calf, with 3 consecutive hyperspectral images at each location. EVIDENCE SYNTHESIS: The literature review identified 9 studies, including 2 of healthy volunteers, 4 of patients with diabetes mellitus, and 3 of patients with peripheral arterial disease. In 5 of 7 patient studies, HSI values were associated with severity of disease or wound healing. In our study, the healthy volunteers' HSI values for oxyhemoglobin, deoxyhemoglobin, and oxygen saturation were (mean±SD) 82.8±24, 55.7±15.7, and 59.2±11.7, respectively, at the plantar surface of the foot, and 40.8±11, 38.0±7.8, and 51.7±10.5, respectively, at the lateral side of the calf. HSI values differed significantly between the calf and plantar locations. Intraoperator reliability between the 3 consecutive images ranged from 81% to 89%. CONCLUSIONS: Limited evidence indicates that HSI is associated with severity of peripheral arterial disease and diabetes mellitus, and with wound healing. Hyperspectral images with a portable system can be taken with high precision when a standardized measurement protocol is used. However, differences exist at several locations at the lower extremity, so each measurement location should be used as its own reference when consecutive measurements are performed during follow-up. More studies with larger patient cohorts should be performed before HSI can be incorporated as standard tool in the diagnostic armamentarium of the vascular specialist.

Quantification of muscle mass in the legs of patients with peripheral arterial occlusive disease: associations between volumetric and cross-sectional single-slice measurements for identification of atrophy and focal sarcopenia.

BACKGROUND: Sarcopenia, commonly determined by measuring skeletal muscle mass index (SMI) at the third lumbar level, has been identified as a predictor of clinical outcome in a variety of diseases. For patients with peripheral arterial occlusive disease (PAOD), we hypothesized that lower extremity SMI (LESMI) might be a more precise predictor of outcome and the extent of chronic ischemia than the systemic muscle mass at the L3 level. We investigated the association between complete muscle volume and muscle area derived with single-slice 2-dimensional measurements in the legs to identify at which level cross-sectional single-slice measurements are most representative of the muscle volume and investigated whether LESMI is associated with systemic sarcopenia and PAOD severity. METHODS: Muscle volumes and areas were semiautomatically segmented from computed tomography (CT) scans of the affected and contralateral legs of 50 PAOD patients with Fontaine stage IIb and 50 PAOD patients with Fontaine stage IV. The muscle mass was determined for the complete volumes of the upper and lower legs and for cross-sectional slices at 40%, 50%, and 60% of the length of the femur and tibia. Patients were determined as sarcopenic based on sex-specific cut-off values at the L3 spinal segment. Two observers segmented 20 randomly selected patients to determine the interobserver reliability with the intraclass correlation coefficient. RESULTS: The correlation between the LESMI of the complete muscle volume and the three cross-sectional slices in all 200 upper and 200 lower legs was moderately strong to strong. Interobserver reliability of cross-sectional slice segmentation was excellent. The LESMI, both measured volumetrically and cross-sectionally, were significantly lower in patients with sarcopenia compared to patients without sarcopenia. The LESMI was lower in patients with Fontaine stage IV compared to patients with Fontaine stage IIb for both volumetric and cross-sectional measurements. CONCLUSIONS: Segmentation of skeletal muscle mass from cross-sectional single-slice CT in the upper and lower leg can accurately and precisely substitute complete volume segmentations. These findings warrant the use of measurements based on cross-sectional single-slice CT for assessing the LESMI. Patients with systemic sarcopenia are also at increased risk for muscle mass loss in the lower extremities. In the current study, LESMI was lower in patients with Fontaine class IV PAOD compared to patients with Fontaine class IIb PAOD. Future studies should assess the predictive value of the LESMI on clinical outcomes in PAOD patients.

Telemedicine in patients with peripheral arterial disease: is it worth the effort?

Introduction: For patients with peripheral arterial disease (PAD), the various components of telemedicine, such as telemonitoring, telecoaching, and teleconsultation, could be valuable in daily management. The objective of this review was to give an overview of the current use of telemedicine interventions in PAD. Areas covered: A literature search was performed for studies that evaluated patients with PAD of the aorto-pedal trajectory, who were monitored by telemedicine and acted upon accordingly. The primary outcome was health-related outcomes. The studies that were found focused mainly on wearable activity monitoring and telecoaching in PAD (n = 4) or wound monitoring after vascular surgery (n = 2). Main results indicate that telemedicine interventions are able to detect (post-operative) complications early, improve functional capacity and claudication onset time, and improve PAD patients' quality of life. Expert opinion: The use of telemedicine in PAD patients is still an under-explored area. Studies investigating the use of telemedicine in PAD are very limited and show varying results. Owing to its high potential in improving physical ability, lifestyle coaching, and timely detection of deterioration, future research should focus on proper implementation of telemedicine in PAD patients, including clinical and feasibility outcomes, effect on workload of nurses, and cost-efficiency.

A systematic review of diagnostic techniques to determine tissue perfusion in patients with peripheral arterial disease.

Introduction: Peripheral arterial disease (PAD) may cause symptoms due to impaired tissue perfusion of the lower extremity. So far, assessment of PAD is mainly performed by determination of stenosis or occlusion in the large arteries and does not focus on microcirculation. Several diagnostic techniques have been recently introduced that may enable tissue perfusion measurements in the lower limb; however, most have not yet been implemented in clinical daily practice. This systematic review provides an overview of these diagnostic techniques and their ability to accurately detect PAD by peripheral tissue perfusion. Areas covered: A literature search was performed for articles that described a diagnostic technique to determine tissue perfusion in patients with known PAD compared with healthy controls. Expert opinion: So far, transcutaneous oxygen measurements are most often used to measure tissue oxygenation in PAD patients, but evidence seems too low to define this technique as a gold standard, and implementing this technique for home monitoring is difficult. New potentially suitable diagnostic tests should be non-invasive, contact-free, and quick. Further research is needed for all of these techniques before broad implementation in clinical use is justified, in hospital, and for home monitoring.