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Background: The most severe diabetic foot ulcers are those related with critical ischemia, which is primarily diagnosed with non-invasive diagnostics. However, these diagnostics have several disadvantages. For example, they only provide global indications of the (macro)level of ischemia. A potential solution can be found in novel optical imaging techniques for local assessment of the microcirculation in diabetic foot ulcers. This review provides an overview of these imaging techniques (laser Doppler perfusion imaging, laser speckle contrast imaging; photoacoustic imaging and hyperspectral imaging) and their applicability for the diagnostic assessment of microcirculation in diabetic foot ulcers. Method: For each technique, the following parts are described: a) their technical background; b) general clinical applications; and, c) its application for microcirculation assessment in diabetic foot ulcers. Parts a-b are based on a narrative review of the literature, part c on a systematic review that was performed in the database Scopus, covering the period from January 1, 2000 to November 31, 2017. Results: Each of these techniques has specific advantages and disadvantages for imaging microcirculation. Potential clinical use depends on measurement aims, and clinical relevance. However, none of the techniques has a strongly established clinical relevance yet: we found a limited number of publications describing clinical outcomes. Future research is needed to determine which technique is the most clinically relevant for the assessment of microcirculation in diabetic foot ulcers. Conclusion: Although promising, the currently available novel optical techniques need to be further improved technically and prospective trials are necessary to evaluate their clinical value.
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... LSCI provides real-time, non-contact imaging of the superficial microcirculation of foot tissue, and images a large tissue area [9]. Therefore, LSCI could be an eligible tool for the assessment of microcirculation in patients with diabetic foot ulcers [10,11]. ...
... LSCI is a technique that can image and estimate blood flow in tissue down to a depth of 1-1.5 mm [10]. When coherent light is diffusely backscattered by a medium, it forms an interference pattern also called a speckle pattern. ...
... When LSCI is applied to assess diabetic foot ulcers, different regions of interest (ROIs) can be assessed simultaneously. This is useful, since both the ulcer and the ulcer edge are of particular interest, and also allows for analysis of multiple ulcers on one foot [10]. Currently, ROIs have to be drawn manually to analyze the measurements. ...
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Foot ulcers are a severe complication of diabetes mellitus. Assessment of the vascular status of diabetic foot ulcers with Laser Speckle Contrast Imaging (LSCI) is a promising approach for diagnosis and prognosis. However, manual assessment during analysis of LSCI limits clinical applicability. Our aim was to develop and validate a fast and robust tracking algorithm for semi-automatic analysis of LSCI data. The feet of 33 participants with diabetic foot ulcers were recorded with LSCI, including at baseline, during the Post-Occlusive Reactive Hyperemia (PORH) test, and during the Buerger’s test. Different regions of interest (ROIs) were used to measure microcirculation in different areas of the foot. A tracking algorithm was developed in MATLAB to reposition the ROIs in the LSCI scans. Manual- and algorithm-tracking of all recordings were compared by calculating the Intraclass Correlation Coefficient (ICC). The algorithm was faster in comparison with the manual approach (90 s vs. 15 min). Agreement between manual- and algorithm-tracking was good to excellent during baseline (ICC = 0.896–0.984; p < 0.001), the PORH test (ICC = 0.790–0.960; p < 0.001), and the Buerger’s test (ICC = 0.851–0.978; p < 0.001), resulting in a tracking algorithm that delivers assessment of LSCI in diabetic foot ulcers with results comparable to a labor-intensive manual approach, but with a 10-fold workload reduction.
... Novel optical imaging techniques such as laser speckle contrast imaging (LSCI) are available to complement the currently used non-invasive blood pressure measurements in people with diabetic foot disease [14]. LSCI is a non-invasive optical imaging technique able to measure blood flow in the skin [15,16]. ...
... In general, the reproducibility of LSCI is high, and it has low inter-subject variability [17][18][19][20]. LSCI is an interesting technique to measure blood flow in diabetic foot disease, because it has a widely validated track record of non-invasive in vivo blood flow measurements compared with other established methods of large-area microcirculation [14]. Furthermore, LSCI can provide non-invasive real-time feedback on changes in perfusion, and is able to monitor the microcirculation in the outer layer of the skin. ...
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Diagnosis of peripheral artery disease in people with diabetes and a foot ulcer using current non-invasive blood pressure measurements is challenging. Laser speckle contrast imaging (LSCI) is a promising non-invasive technique to measure cutaneous microcirculation. This study investigated the association between microcirculation (measured with both LSCI and non-invasive blood pressure measurement) and healing of diabetic foot ulcers 12 and 26 weeks after measurement. We included sixty-one patients with a diabetic foot ulcer in this prospective, single-center, observational cohort-study. LSCI scans of the foot, ulcer, and ulcer edge were conducted, during baseline and post-occlusion hyperemia. Non-invasive blood pressure measurement included arm, foot, and toe pressures and associated indices. Healing was defined as complete re-epithelialization and scored at 12 and 26 weeks. We found no significant difference between patients with healed or non-healed foot ulcers for both types of measurements (p = 0.135–0.989). ROC curves demonstrated moderate sensitivity (range of 0.636–0.971) and specificity (range of 0.464–0.889), for LSCI and non-invasive blood pressure measurements. Therefore, no association between diabetic foot ulcer healing and LSCI-measured microcirculation or non-invasive blood pressure measurements was found. The healing tendency of diabetic foot ulcers is difficult to predict based on single measurements using current blood pressure measurements or LSCI.
... Diabetic foot (DF) represents one of the most serious and expensive complications of diabetes and is subject to a high percentage of amputations [1][2][3][4]. ...
... Trauma also plays a significant part in the development of ulceration. Diabetic foot ulcers are a common complication in patients with uncontrolled diabetes and are the most common cause of non-traumatic amputations [4,[8][9][10]. Evidence in the literature suggests that the early detection and treatment of diabetic foot complications could reduce the prevalence of ulceration by 44% to 85%. ...
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Introduction: Diabetic foot represents one of the most serious and expensive complications of diabetes and is subject to a high percentage of amputations that are almost always preceded by ulcers ascribable to neuropathy and/or vasculopathy. Videocapillaroscopy (VCS) can be a valuable aid in order to uncover morpho-structural anomalies in the vascular bed, both at the level of the oral mucosa and at the level of the terminal vessels of the lower limb. Materials and methods: Sixty subjects divided into 4 groups were enrolled: 15 healthy subjects; 15 patients with diabetes for more than 10 years without ulcerative foot lesions; 15 patients with neuropathic diabetic foot (clinical diagnosis, MDNS); 15 patients with ischemic diabetic foot (clinical diagnosis, ABI, lower limb doppler). A complete videocapillaroscopic mapping of the oral mucosa was carried out on each patient. The areas investigated were: labial mucosa, the retro-commissural region of the buccal mucosa, and the vestibular masticatory mucosa (II and V sextant). Results: The analysis of the morphological and densitometric characteristics of the capillaries revealed the following: a significant reduction in capillary density in neuropathic (mean ± SD 7.32 ± 2.1) and ischemic patients (mean ± SD 4.32 ± 3.2) compared to the control group of patients (both diabetic mean ± SD 12.98 ± 3.1 and healthy mean ± SD 19.04 ± 3.16) (ANOVA test and Bonferroni t test p < 0.05); a reduction in the average length of the capillaries and a significant increase in tortuosity (ANOVA test and Bonferroni t test p < 0.05). In the neuropathic patients, a recurrent capillaroscopic pattern that we defined as "sun" was found, with capillaries arranged radially around an avascular area. Conclusions: The data obtained from this preliminary study suggest a potential diagnostic role of oral capillaroscopy in the early and subclinical identification of microangiopathic damage in patients with diabetic foot.
... Identification of specific vascular patterns in formations contributes to the diagnosis of malignant skin lesions. The most common approaches to non-invasive vessel imaging are optical microscopy 10,11 , laser speckle contrast imaging 12 , laser Doppler perfusion imaging 13 and optical coherence tomography 14 . Their practical use is limited due to inevitable motion of the inspected area caused by body vibrations, patient breathing and other factors [15][16][17][18] . ...
... Some novel and promising optical techniques for imaging of microcirculation in the diabetic foot were evaluated, however, such as laser Doppler perfusion imaging, laser speckle contrast imaging, photoacoustic imaging and hyperspectral imaging. 19 However, the relevant clinical verifications and values had not been carried out. The current clinical methods such as laser Doppler flowmetry, 20,21 nailfold microcirculation index 22,23 and capillaroscopy 24,25 were all suitable for detecting capillary microcirculation in finger-tip skin due to the limitation of penetration, but could not detect capillary microcirculation in subcutaneous fat and muscle tissue. ...
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Objective: To evaluate the foot microcirculation in type 2 diabetes mellitus (T2DM) and impaired glucose tolerance patients (IGT) with contrast-enhanced ultrasound (CEUS). Methods: The study included 37 patients with T2DM but without diabetic foot (DM group), 15 patients with impaired glucose tolerance (IGT group) and 10 elderly males with normal fasting blood glucose (FBS) and negative glucose tolerance tests (control group). Color Doppler flow imaging (CDFI) and CEUS were performed on the right foot great toes for detecting the blood perfusion performance. CEUS images were recorded and parameters of CDFI and flow time-intensity curves (TICs) were analyzed by the Student's t-test. Results: There was no significant difference in CDFI parameters pulse index and peak systolic blood flow velocity (PSV) among the three groups (P >0.05). Compared with control group, CEUS images of IGT and DM groups showed lower microvascular density and were pale. Peak intensity (PI) and area under time-intensity curve (AUC) in control, IGT and DM groups were decreased gradually (PI 46.36±10.96 vs 35.26±11.65 vs 28.15±7.94, P = 0.001, AUC 5.12±1.02 vs 3.25±1.60 vs 2.81±1.20, P = 0.001). The arrival times (AT) and time to peak (TTP) tended to be increased with the extension of DM course, but the difference was not statistically significant (AT, P = 0.260, TTP, P = 0.481). Conclusion: CEUS, as a noninvasive and valuable technique, could detect the alterations in foot microcirculation of DM and IGT patients.
... In this case, microvasculature mapping and quantitative parameters monitoring provides an ability of early in vivo pathology detection and diagnosis. Several approaches to non-invasive microcirculation optical imaging are reported [4][5][6][7][8][9], but mainly microcirculation imaging is implemented in the nailfold area [10][11][12]. Despite the ability of capillaries comprehensive characterization available for nailfold capillaroscopy, the most valuable data is to be acquired by the exact microvasculature imaging around arbitrary located inflammation area. ...
... Main approaches to non-invasive microcirculation imaging are optical microscopy [8][9][10], laser Doppler perfusion imaging [11,12], laser speckle contrast imaging [13,14] and optical coherence tomography [15]. Advantages and drawbacks of these approaches as well as their clinical applications are well analyzed [16][17][18]. ...
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The capillary system immediately responds to many pathologies and environmental conditions. Accurate monitoring of its functioning often enables early detection of various diseases related to disorders in skin microcirculation. To expand the scope of capillaroscopy application, it is reasonable to visualize and assess blood microcirculation exactly in the areas of inflamed skin. Body vibrations, breathing, non-flat skin surface and other factors hamper the application of conventional capillaroscopes outside the nailfold area. In this paper, we propose an exoscope-based optical system for high-quality non-invasive computational imaging of capillary network in various areas of the body. Accurate image matching and tracking temporal intensity variations allow detecting the presence of blood pulsations, precise mapping of capillaries and photoplethysmogram acquisition. We have demonstrated the efficiency of the proposed approach experimentally by in vivo mapping and analysis of microvessels in wrist, forearm, upper-arm, breast and hip areas. We believe that the developed system will increase the diagnostic value of video capillaroscopy in clinical practice. © 2021 Optical Society of America under the terms of the OSA Open Access Publishing Agreement
... Another example where the spatial information is important is in patients with sepsis, where a significant spatial heterogeneity can be observed in the microcirculation. 28 It has also been suggested that LSCI could become a useful tool for monitoring diabetic foot ulcers, 29 where most studies to date have used laser Doppler perfusion imaging, 30 and, therefore, the MELSCI system that we have suggested may be important due to its LDF mimicking properties. The increased quality in the pulsatile signal in P ANN compared to the single-exposure models is also interesting. ...
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Significance: Multi-exposure laser speckle contrast imaging (MELSCI) estimates microcirculatory blood perfusion more accurately than single-exposure LSCI. However, the technique has been hampered by technical limitations due to massive data throughput requirements and nonlinear inverse search algorithms, limiting it to an offline technique where data must be postprocessed. Aim: To present an MELSCI system capable of continuous acquisition and processing of MELSCI data, enabling real-time video-rate perfusion imaging with high accuracy. Approach: The MELSCI algorithm was implemented in programmable hardware (field programmable gate array) closely interfaced to a high-speed CMOS sensor for real-time calculation. Perfusion images were estimated in real-time from the MELSCI data using an artificial neural network trained on simulated data. The MELSCI perfusion was compared to two existing single-exposure metrics both quantitatively in a controlled phantom experiment and qualitatively in vivo. Results: The MELSCI perfusion shows higher signal dynamics compared to both single-exposure metrics, both spatially and temporally where heartbeat-related variations are resolved in much greater detail. The MELSCI perfusion is less susceptible to measurement noise and is more linear with respect to laser Doppler perfusion in the phantom experiment (R2 = 0.992). Conclusions: The presented MELSCI system allows for real-time acquisition and calculation of high-quality perfusion at 15.6 frames per second.
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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.
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Peripheral artery disease (PAD) is a flow-limiting condition caused by narrowing of the peripheral arteries typically due to atherosclerosis. It affects almost 200 million people globally with patients either being asymptomatic or presenting with claudication or critical or acute limb ischemia. PAD-affected patients display increased mortality rates, rendering their management critical. Endovascular interventions have proven crucial in PAD treatment and decreasing mortality and have significantly increased over the past years. However, for the functional assessment of the outcomes of revascularization procedures for the treatment of PAD, the same tests that have been used over the past decades are still being employed. Those only allow an indirect evaluation, while an objective quantification of limb perfusion is not feasible. Standard intraarterial angiography only demonstrates post-intervention vessel patency, hence is unable to accurately estimate actual limb perfusion and is incapable of quantifying treatment outcome. Therefore, there is a significant necessity for real-time objectively measurable procedural outcomes of limb perfusion that will allow vascular experts to intraoperatively quantify and assess outcomes, thus optimizing treatment, obviating misinterpretation, and providing significantly improved clinical results. The purpose of this review is to familiarize readers with the currently available perfusion-assessment methods and to evaluate possible prospects.
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We evaluate a portable ultrasound and photoacoustic imaging (PAI) system for the feasibility of a point-of-care assessment of clinically evident synovitis. Inflamed and non-inflamed proximal interphalangeal joints of 10 patients were examined and compared with joints from 7 healthy volunteers. PAI scans, ultrasound power Doppler (US-PD), and clinical examination were performed. We quantified the amount of photoacoustic (PA) signal using a region of interest (ROI) drawn over the hypertrophic joint space. PAI response was increased 4 to 10 fold when comparing inflamed with contralateral non-inflamed joints and with joints from healthy volunteers (p < 0.001 for both). US-PD and PAI were strongly correlated (Spearman’s ρ = 0.64, with 95% CI: 0.42, 0.79). Hence, PAI using a compact handheld probe is capable of detecting clinically evident synovitis. This motivates further investigation into the predictive value of PAI, including multispectral PAI, with other established modalities such as US-PD or MRI.
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Lower extremity amputation (LEA) in patients with diabetes results in high mortality, reduced quality of life, and increased medical costs. Exact data on incidences of LEA in diabetic and non-diabetic patients are important for improvements in preventative diabetic foot care, avoidance of fatal outcomes, as well as a solid basis for health policy and the economy. However, published data are conflicting, underlining the necessity for the present systematic review of population-based studies on incidence, relative risks and changes of amputation rates over time. It was conducted according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Nineteen out of 1582 studies retrieved were included in the analysis. The incidence of LEA in the diabetic population ranged from 78 to 704 per 100,000 person-years and the relative risks between diabetic and non-diabetic patients varied between 7.4 and 41.3. Study designs, statistical methods, definitions of major and minor amputations, as well as the methods to identify patients with diabetes differed greatly, explaining in part these considerable differences. Some studies found a decrease in incidence of LEA as well as relative risks over time. This obvious lack of evidence should be overcome by new studies using a standardized design with comparable methods and definitions. Systematic review registration number PROSPERO CRD4201501780
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Introduction Laser speckle imaging is used for noninvasive assessment of blood flow of cutaneous wounds. The aim of this study was to assess if laser speckle imaging can be used as a predictor of venous ulcer healing. Methods After generating the flux speckle images, three regions of interest (ROI) were identified to measure the flow. Sensitivity, specificity, negative predictive value, and positive predictive value for ulcer healing were calculated. Results In total, 17 limbs were included. A sensitivity of 92.3%, specificity of 75.0%, PPV of 80.0%, and NPV 75.0% were found in predicting wound healing based on laser speckle images. Mean flux values were lowest in the center (ROI I) and showed an increase at the wound edge (ROI II, p = 0.03). Conclusion Laser speckle imaging shows acceptable sensitivity and specificity rates in predicting venous ulcer healing. The wound edge proved to be the best probability for the prediction of wound healing.
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Currently, imaging technologies that enable dermsurgeons to visualize non-melanoma skin cancers (NMSC) in vivo preoperatively are lacking, resulting in excessive or incomplete removal. Multispectral optoacoustic tomography (MSOT) is a volumetric imaging tool to differentiate tissue chromophores and exogenous contrast agents, based on differences in their spectral signatures and used for high-resolution imaging of functional and molecular contrast at centimeter scale depth. We performed MSOT imaging with two- and three-dimensional handheld scanners on 21 Asian patients with NMSC. The tumors and their oxygenation parameters could be distinguished from normal skin endogenously. The lesion dimensions and depths were extracted from the spectral melanin component with three-dimensional spatial resolution up to 80 μm. The intraclass correlation coefficient correlating tumor dimension measurements between MSOT and ex vivo histology of excised tumors, showed good correlation. Real-time 3D imaging was found to provide information on lesion morphology and its underlying neovasculature, indicators of the tumor’s aggressiveness.
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Objective: To evaluate ambulatory clinical cases of diabetic foot ulcers (DFUs) and diabetic foot infections (DFIs) in the U.S. from 2007 to 2013 and to assess outcomes of emergency department or inpatient (ED/IP) admission, number of clinic visits per year, and physician time spent per visit. Research design and methods: A cross-sectional historical cohort analysis was conducted by using the nationally representative Centers for Disease Control and Prevention National Ambulatory Medical Care Survey data from 2007 to 2013, including patients age ≥18 years with diabetes and either DFIs or DFUs. Study outcomes were analyzed by using generalized linear models controlling for key demographics and chronic conditions. Results: Across the estimated 5.6 billion ambulatory care visits between 2007 and 2013, 784.8 million involved diabetes and ∼6.7 million (0.8%) were for DFUs (0.3%) or DFIs (0.5%). Relative to other ambulatory clinical cases, multivariable analyses indicated that DFUs were associated with a 3.4 times higher odds of direct ED/IP admission (CI 1.01-11.28; P = 0.049), 2.1 times higher odds of referral to another physician (CI 1.14-3.71; P = 0.017), 1.9 times more visits in the past 12 months (CI 1.41-2.42; P < 0.001), and 1.4 times longer time spent per visit with the physician (CI 1.03-1.87; P = 0.033). DFIs were independently associated with a 6.7 times higher odds of direct ED referral or IP admission (CI 2.25-19.51; P < 0.001) and 1.5 times more visits in the past 12 months (CI 1.14-1.90; P = 0.003). Conclusions: This investigation of an estimated 6.7 million diabetic foot cases indicates markedly greater risks for both ED/IP admissions and number of outpatient visits, with DFUs also associated with a higher odds of referrals to other physicians and longer physician visit times.
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