Non invasive blood flow assessment in diabetic foot ulcer using laser speckle contrast imaging technique
04 Mar 2014-Proceedings of SPIE (International Society for Optics and Photonics)-Vol. 8952, pp 169-177
TL;DR: A noninvasive, noncontact and whole field laser speckle contrast imaging (LSCI) technique has been described in this paper which is used to assess the changes in blood flow in diabetic ulcer affected areas of the foot.
Abstract: Measuring microcirculatory tissue blood perfusion is of interest for both clinicians and researchers in a wide range of applications and can provide essential information of the progress of treatment of certain diseases which causes either an increased or decreased blood flow. Diabetic ulcer associated with alterations in tissue blood flow is the most common cause of non-traumatic lower extremity amputations. A technique which can detect the onset of ulcer and provide essential information on the progress of the treatment of ulcer would be of great help to the clinicians. A noninvasive, noncontact and whole field laser speckle contrast imaging (LSCI) technique has been described in this paper which is used to assess the changes in blood flow in diabetic ulcer affected areas of the foot. The blood flow assessment at the wound site can provide critical information on the efficiency and progress of the treatment given to the diabetic ulcer subjects. The technique may also potentially fulfill a significant need in diabetic foot ulcer screening and management.
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TL;DR: LSCI is a stable and reproducible technique for assessment of microcirculation in people with diabetic foot ulcers and shows significant differences between non-ischemic, ischemic and critical-ISChemic patient populations.
Abstract: OBJECTIVE: A major challenge for treating diabetic foot ulcers is estimating the severity of ischemia, as the currently used non-invasive diagnostic techniques provide relatively poor prognostic values. Laser speckle contrast imaging (LSCI) is a promising non-invasive technique to assess microcirculation. Our aim was to investigate the stability and reproducibility of LSCI for the assessment of microcirculation in the diabetic foot, the relation of LSCI results to currently used non-invasive blood pressure measurements, and the ability of LSCI to discriminate between the degrees of ischemia. APPROACH: Thirty-three participants with diabetic foot ulcers were included in this prospective, single centre, observational cohort study that was conducted in the Netherlands. They were classified as non-ischemic, ischemic or critical-ischemic based on criteria formulated in the international guidelines. Two clinicians performed LSCI scans of the foot, consisting of baseline measurements, followed by two stress tests (post-occlusion peak and elevation test). With three measurement conditions and five regions of interest of the foot per patient, a total of 15 measurements were available for analyses. MAIN RESULTS: The intra-observer agreement of LSCI was high (interclass correlation coefficient (ICC) = 0.711-0.950; p < 0.001) for all 15 measurements. The inter-observer agreement was high (ICC = 0.728-0.861; p ⩽ 0.001) for 10 measurements and moderate (ICC = 0.476-0.570; p ⩽ 0.005) for the remaining five measurements. The inter-assessor agreement was high and significant (ICC = 0.857-0.996; p ⩽ 0.001) for all measurements. Correlation between LSCI and non-invasive blood pressure measurements was low (ICC = -0.272-0.582). During both stress tests, microcirculation was significantly lower in critical-ischemic feet compared to non-ischemic feet (67.5 perfusion units (PU) versus 96.3 PU and 41.0 PU versus 63.9 PU; p < 0.05). SIGNIFICANCE: LSCI is a stable and reproducible technique for assessment of microcirculation in people with diabetic foot ulcers and shows significant differences between non-ischemic, ischemic and critical-ischemic patient populations.
28 citations
TL;DR: The current state‐of‐the‐art biophotonics technologies used to identify the complications of diabetes mellitus and assess the quality of their treatment are reviewed.
Abstract: The prevalence of diabetes complications is a significant public health problem with a considerable economic cost. Thus, the timely diagnosis of complications and prevention of their development will contribute to increasing the length and quality of patient life, and reducing the economic costs of their treatment. This article aims to review the current state-of-the-art biophotonics technologies used to identify the complications of diabetes mellitus and assess the quality of their treatment. Additionally, these technologies assess the structural and functional properties of biological tissues, and they include capillaroscopy, laser Doppler flowmetry and hyperspectral imaging, laser speckle contrast imaging, diffuse reflectance spectroscopy and imaging, fluorescence spectroscopy and imaging, optical coherence tomography, optoacoustic imaging and confocal microscopy. Recent advances in the field of optical noninvasive diagnosis suggest a wider introduction of biophotonics technologies into clinical practice and, in particular, in diabetes care units.
17 citations
22 Oct 2014
TL;DR: Simple and low cost LASCI connection kit for mobile phone and its comparison to laser Doppler perfusion imager are demonstrated and local thermal hyperemia tests are used to compare both techniques and to demonstrate the potential of LAS CI device.
Abstract: Assessment of skin blood flow is of interest for evaluation of skin viability as well as for reflection of the overall condition of the circulatory system. Laser Doppler perfusion imaging (LDPI) and laser speckle contrast imaging (LASCI) are optical techniques used for assessment of skin perfusion. However, these systems are still too expensive and bulky to be widely available. Implementation of such techniques as connection kits for mobile phones have a potential for primary diagnostics. In this work we demonstrate simple and low cost LASCI connection kit for mobile phone and its comparison to laser Doppler perfusion imager. Post-occlusive hyperemia and local thermal hyperemia tests are used to compare both techniques and to demonstrate the potential of LASCI device.
12 citations
Cites background from "Non invasive blood flow assessment ..."
...LASCI can be used for monitoring of port wine stain treatment [8], assessment of burn injuries [9] and diabetic foot ulcers [10], quantification of the Allen test [11], label free in vivo imaging of blood and lymph vessels [12] as well as skin roughness measurements [13]....
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TL;DR: The presented MELSCI system allows for real-time acquisition and calculation of high-quality perfusion at 15.6 frames per second and shows higher signal dynamics compared to both single-exposure metrics, both spatially and temporally.
Abstract: Noninvasive in vivo imaging of microcirculatory blood flow or perfusion (average speed times concentration of moving red blood cells) is of interest in several clinical applications, including monitoring of burn wounds1,2 and investigation of peripheral arterial disease,3 as well as several others.4 One technique that has gained a lot of focus in the last decades is laser speckle contrast imaging [LSCI; sometimes laser speckle contrast analysis (LASCA)] in which tissue is illuminated with a laser and the resulting speckle pattern is detected with a camera. Light that scatters when interacting with moving particles in the tissue will obtain a Doppler frequency shift depending on the velocity of the particles. The interference of light with different frequencies will give rise to fluctuations in the speckle pattern formed on the imaging sensor. The movement of the speckles on the sensor will cause an image blur that increases with exposure time. The local spatial statistics of this blur can be related to the movement of particles in the tissue, as is done in LSCI.5
LSCI has been increasingly used over laser Doppler imaging mainly due to its simple setup and fast acquisition and data processing. However, conventional LSCI has drawbacks such as a nonlinear response to perfusion, dependency to static scattering contrast, and a high variability in the presence of noise.5,6 Recent work has gone into calibrating and correcting for these issues to make LSCI a more accurate technique.7 Despite this, while it is generally accepted that LSCI is related to microcirculatory perfusion, the relationship is complex and a direct mapping is still not known.4,8 For the older laser Doppler flowmetry (LDF) technique, the relation to microcircular perfusion is better understood, where it is, for example, possible to theoretically show that the perfusion estimate is linearly related to the flow speed.9,10
To address the nonlinearity of LSCI to perfusion, Parthasarathy et al.11 proposed a new setup using multiple exposure times. The technique, called multi-exposure laser speckle contrast imaging (MELSCI, sometimes MESI), obtains information about the speckle motion blur at various exposures, enabling more advanced models to be used when estimating perfusion from the contrast.5,12 Several approaches to capture multi-exposure images have been proposed. The initial approach by Parthasarathy et al.11 was to use a time-modulated laser to achieve multi-exposure images. By capturing all images with a fixed exposure time but only illuminating the tissue during parts of that time, multi-exposures can be generated. However, a problem with this approach is that images with different exposure times are separated in time since they are captured sequentially. Dragojevic et al.13 suggested another approach that addressed this drawback. This was based on a high-speed camera, only capturing images at the shortest exposure time required, and in postprocessing adding successive images together to create longer exposure times. These synthetic exposure times are valid if the interframe delay in the camera is negligible. This method is faster and more accurate than previous methods due to all exposure times essentially being captured simultaneously, but it produces immense amounts of data that must be transferred and processed. At the time, this was, therefore, limited to an offline technique. Hence, MELSCI has so far been held back by technical limitations in both the imaging setup and the computation time of the models.
To address this problem of a data and processing bottleneck, we have previously presented a system for synthetic MELSCI,14 based on a high-speed 1000-frames per second (fps) 1-megapixel camera directly interfaced to a field programmable gate array (FPGA) performing the multi-exposure contrast algorithm outlined by Dragojevic13 in real-time. Processed contrast images were sent to a computer, massively reducing the data throughput requirements. This system could produce multi-exposure contrast images at 15.6 fps, using all available frames from the 1000-fps camera, without any loss of data. However, due to insufficient processing power, the system was not able to transfer the processed images to the computer fast enough, and thus could not provide a real-time video-rate output. Furthermore, while the calculation of multi-exposure contrast images was fast enough, at the time there was no multi-exposure perfusion algorithm fast enough to keep up with the continuous stream of contrast images. The model proposed by Parthasarathy et al.11 and later refined by Kazmi et al.15 requires nonlinear fitting to extract perfusion-related parameters from the multi-exposure contrast. This process must be performed individually in each pixel for full field perfusion images, which is not feasible in real-time with satisfactory frame rates.6
We have previously presented a method using machine learning and simulated data from thousands of Monte Carlo tissue models from which we train an artificial neural network (ANN) to translate multi-exposure contrast to laser Doppler perfusion. We showed that this technique not only achieves a model-inference time of <30 ms per image, but also has higher accuracy and less susceptibility to noise than other available models.6
The aim of this paper is to present a complete system for continuous real-time video-rate perfusion imaging using both our previous methods in an integrated processing pipeline. We validate the accuracy of the perfusion estimate in a controlled phantom experiment and present results from an occlusion-release provocation of the forearm of a healthy subject. We use these measurements to compare both the quantitative and qualitative similarities and differences between our perfusion estimate and two common single-exposure metrics.
10 citations
TL;DR: This study reveals a set of “landmarks”—key physiological and molecular events in the healing process—that can serve as a standardized framework for describing the impact of emerging PAD treatments, and paves the road for more efficient translation of PAD research.
Abstract: Background: Peripheral arterial disease (PAD) is a major worldwide health concern. Since the late 1990s therapeutic angiogenesis has been investigated as an alternative to traditional PAD treatments. Although positive preclinical results abound in the literature, the outcomes of human clinical trials have been discouraging. Among the challenges the field has faced has been a lack of standardization of the timings and measures used to validate new treatment approaches. Methods: In order to study the spatiotemporal dynamics of both perfusion and neovascularization in mice subjected to surgically-induced hindlimb ischemia (n= 30), we employed three label-free imaging modalities (a novel high-sensitivity ultrasonic Power Doppler methodology, laser speckle contrast, and photoacoustic imaging), as well as a tandem of radio-labeled molecular probes, 99mTc-NC100692 and 99mTc-BRU-5921 respectively, designed to detect two key modulators of angiogenic activity, αVβ3 and HIF-1α , via scintigraphic imaging. Results: The multimodal imaging strategy reveals a set of "landmarks"-key physiological and molecular events in the healing process-that can serve as a standardized framework for describing the impact of emerging PAD treatments. These landmarks span the entire process of neovascularization, beginning with the rapid decreases in perfusion and oxygenation associated with ligation surgery, extending through pro-angiogenic changes in gene expression driven by the master regulator HIF-1α , and ultimately leading to complete functional revascularization of the affected tissues. Conclusions: This study represents an important step in the development of multimodal non-invasive imaging strategies for vascular research; the combined results offer more insight than can be gleaned through any of the individual imaging methods alone. Researchers adopting similar imaging strategies and will be better able to describe changes in the onset, duration, and strength of each of the landmarks of vascular recovery, yielding greater biological insight, and enabling more comprehensive cross-study comparisons. Perhaps most important, this study paves the road for more efficient translation of PAD research; emerging experimental treatments can be more effectively assessed and refined at the preclinical stage, ultimately leading to better next-generation therapies.
8 citations
Cites methods from "Non invasive blood flow assessment ..."
...US and LSCI images were obtained at multiple time points before and after femoral artery ligation....
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...aimed at imaging blood perfusion using ultrasound (US) [16,17], photoacoustic imaging (PA) [18–21], and laser speckle contrast imaging (LSCI) [22], as well as quantitative molecular imaging approaches using radiolabeled probes targeted at specific angiogenic biomarkers such as matrix metalloproteinases, VEGF isoforms, and αVβ3 integrin [23–31]....
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...Figure 3: Representative LSCI collateral imaging data presented at a series of time points (prior to and following ligation)....
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...The trend for LSCI was obtained by a comparable procedure, but we report the ratio of signal from the right ischemic hindlimb to that of the left control hindlimb: 𝑟𝑟𝑡𝑡,𝑚𝑚 = ⟨𝑝𝑝𝑡𝑡,𝑚𝑚 (𝑅𝑅)⟩/⟨𝑝𝑝𝑡𝑡,𝑚𝑚 (𝐿𝐿) ⟩ where ⟨𝑝𝑝𝑡𝑡,𝑚𝑚 (𝑅𝑅)⟩ and ⟨𝑝𝑝𝑡𝑡,𝑚𝑚 (𝐿𝐿) ⟩ are perfusion averages over the boxes on right and left hindlimbs, respectively....
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...In the LSCI images, the ratio between an ischemic right hindlimb region and its corresponding healthy left hindlimb region was computed, and their difference (plus unity, such that all values are relative to 1) was plotted....
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References
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TL;DR: Defining causal pathways that predispose to diabetic limb amputation suggests practical interventions that may be effective in preventing diabetic limb loss.
Abstract: We defined the causal pathways responsible for 80 consecutive initial lower-extremity amputations to an extremity in diabetic patients at the Seattle Veterans Affairs Medical Center over a 30-mo interval from 1984 to 1987. Causal pathways, either unitary or composed of various combinations of seven potential causes (i.e., ischemia, infection, neuropathy, faulty wound healing, minor trauma, cutaneous ulceration, gangrene), were determined empirically after a synthesis by the investigators of various objective and subjective data. Estimates of the proportion of amputations that could be ascribed to each component cause were calculated. Twenty-three unique causal pathways to diabetic limb amputation were identified. Eight frequent constellations of component causes resulted in 73% of the amputations. Most pathways were composed of multiple causes, with only critical ischemia from acute arterial occlusions responsible for amputations as a singular cause. The causal sequence of minor trauma, cutaneous ulceration, and wound-healing failure applied to 72% of the amputations, often with the additional association of infection and gangrene. We specified precise criteria in the definition of causal pathway to permit estimation of the cumulative proportion of amputations due to various causes. Forty-six percent of the amputations were attributed to ischemia, 59% to infection, 61% to neuropathy, 81% to faulty wound healing, 84% to ulceration, 55% to gangrene, and 81% to initial minor trauma. An identifiable and potentially preventable pivotal event, in most cases an episode involving minor trauma that caused cutaneous injury, preceded 69 to 80 amputations. Defining causal pathways that predispose to diabetic limb amputation suggests practical interventions that may be effective in preventing diabetic limb loss.
1,465 citations
TL;DR: A theory is developed which relates quasi-elastic light scattering measurements to blood flow in tissue micro-vasculature and implies that the time decay of the photon autocorrelation function scales proportionally with cell size and inversely with mean translational speed.
Abstract: A theory is developed which relates quasi-elastic light scattering measurements to blood flow in tissue microvasculature. We assume that the tissue matrix surrounding the blood cells is a strong diffuser of light and that moving erythrocytes, therefore, are illuminated by a spatially distributed source. Because the surrounding tissue is considered to be stationary, Doppler shifts in the frequency of the scattered light arise only from photon interactions with the moving blood cells. The theory implies that the time decay of the photon autocorrelation function scales proportionally with cell size and inversely with mean translational speed. Analysis of multiple interactions of photons with moving cells indicates the manner in which spectral measurements additionally are sensitive to changes in blood volume. Predictions are verified by measurements of particle flow in model tissues.
927 citations
TL;DR: A new noninvasive technique for monitoring capillary blood flow based on the phenomenon of time-varying laser speckle, which provides a velocity map of the area of interest in real time without the need for scanning.
Abstract: A new noninvasive technique for monitoring capillary blood flow has been developed. Based on the phenomenon
of time-varying laser speckle, it is a digital version of single-exposure speckle photography. It
provides a velocity map of the area of interest in real time without the need for scanning. The results of some initial experiments on volunteers are presented.
669 citations
TL;DR: Certain foot deformities, reduced skin oxygenation and foot perfusion, poor vision, greater body mass, and both sensory and autonomic neuropathy independently influence foot ulcers risk, thereby providing support for a multifactorial etiology for diabetic foot ulceration.
Abstract: OBJECTIVE: Little prospective research exists on risk factors for diabetic foot ulcer that considers the independent effects of multiple potential etiologic agents. We prospectively studied the effects of diabetes characteristics, foot deformity, behavioral factors, and neurovascular function on foot ulcer risk among 749 diabetic veterans with 1,483 lower limbs. RESEARCH DESIGN AND METHODS: Eligible subjects included all diabetic enrollees of a general internal medicine clinic without foot ulcer, of whom 83% agreed to participate. Baseline assessment included history and lower-limb physical examination, tests for sensory and autonomic neuropathy, and measurements of macro- and microvascular perfusion in the foot. Subjects were followed for the occurrence of a full thickness skin defect on the foot that took > 14 days to heal, with a mean follow-up of 3.7 years. RESULTS: Using stepwise Cox regression analysis, the following factors were independently related to foot ulcer risk: foot insensitivity to the 5.07 monofilament (relative risk [95% CI]) 2.2 (1.5-3.1), past history of amputation 2.8 (1.8-4.3) or foot ulcer 1.6 (1.2-2.3), insulin use 1.6 (1.1-2.2), Charcot deformity 3.5 (1.2-9.9), 15 mmHg higher dorsal foot transcutaneous PO2 0.8 (0.7-0.9), 20 kg higher body weight 1.2 (1.1-1.4), 0.3 higher ankle-arm index 0.8 (0.7-1.0), poor vision 1.9 (1.4-2.6), and 13 mmHg orthostatic blood pressure fall 1.2 (1.1-1.5). Higher ulcer risk was associated with hammer/claw toe deformity and history of laser photocoagulation in certain subgroups. Unrelated to foot ulcer risk in multivariate models were diabetes duration and type, race, smoking status, diabetes education, joint mobility, hallux blood pressure, and other foot deformities. CONCLUSIONS: Certain foot deformities, reduced skin oxygenation and foot perfusion, poor vision, greater body mass, and both sensory and autonomic neuropathy independently influence foot ulcer risk, thereby providing support for a multifactorial etiology for diabetic foot ulceration.
666 citations
TL;DR: In this article, the velocity distribution in a flow field is mapped on the photograph as variations in speckle contrast, which can be converted to intensity variations by means of a simple spatial filtering technique.
641 citations