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Objective: In patients with systemic sclerosis (SSc) the perfusion of the fingers shows an alteration of the physiological proximal-distal gradient (PDG). The aim of this study is to provide a generalizable definition of PDG, applying it in a cohort of SSc patients and healthy controls (HC) using laser speckle contrast analysis (LASCA)., Methods: Adult consecutive SSc patients and HC were enrolled. Peripheral blood perfusion of the hands was evaluated by LASCA, subsequently obtaining 3 different regions of interest: from the distal interphalangeal joint to the fingertip (DIST), from the metacarpophalangeal joint to the distal interphalangeal joint (PROX), and of the whole finger (TOT). A PDG formula independent of both intra- and inter-personal factors was then built. The PDG formula so obtained was: [(DIST × 2.63) - PROX]/TOT., Results: Ninety-four SSc patients (79.8% female, mean age 58.7 years) were enrolled. Applying the PDG formula, SSc patients revealed mean PDG values significantly lower than HC (1.82 ± 0.44 PU vs 2.70 ± 0.38 PU; p < 0.0001). Patients with a previous history of digital ulcers presented significant lower PDG values (p = 0.002). The ROC curve analysis identified in 2.28 PU the best PDG cut-off value between SSc and HC, with 86% sensibility and 90% specificity., Conclusion: This study provided a PDG formula generalizable to all kind of subjects, applying it in SSc with great sensibility and specificity using LASCA, the best non-invasive imaging technique for the dynamical evaluation of peripheral perfusion. LASCA-PDG appears also as a tool able to identify a subclinical microangiopathic impairment., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: The aim was to investigate perfusion-related changes in the intestinal diffusion assessed by NMR-MOUSE monitoring in minipigs. This was a follow-up study of previous experiments on landrace pigs demonstrating the feasibility of NMR-MOUSE monitoring in large animals., Methods: 5 mature female minipigs (mean body weight 50 ± 2 kg) underwent laparotomy with exposition of several small intestinal loops and their feeding vessels. The loops were examined consecutively using NMR-MOUSE monitoring for assessment of intestinal proton diffusion (fast diffusion component [FC] and slow diffusion component [SC]) and oxygen to see monitoring (O2C, LEA Medizintechnik GmbH, Giessen, Germany) for microcirculatory evaluation. Following a baseline measurement on each loop under physiological perfusion, measurements were continued as one of the following main treatments were performed per loop: method 1 - ischemia; method 2 - flow reduction; method 3 - intraluminal glucose followed by ischemia; method 4 - intraluminal glucose followed by flow reduction. Perioperative monitoring was supplemented by blood gas analyses and histopathological assessment of H.E. stained intestinal biopsies., Results: The NMR-MOUSE measurement showed a significant difference in the change to baseline values in the FC during flow reduction compared to the other treatments according to the unadjusted (p M2 vs. M1  < 0.0001, p M2 vs. M3  = 0.0005, p M2 vs. M4  = 0.0005) and the adjusted p-values (p M2 vs. M1  < 0.0001, p M2 vs. M3  = 0.0030, p M2 vs. M4  = 0.0030). In the SC, the difference between ischemia and flow reduction was significant according to the unadjusted p-values (p M2 vs. M1  = 0.0397). Whereas the FC showed a trend towards ongoing increase during ischemia but towards ongoing decrease during flow reduction, the SC showed contrary trends. These effects seemed to be attenuated by prior glucose application. According to the results of O2C monitoring, ischemia as well as flow reduction caused a significant decrease of microcirculatory oxygen saturation (inner probe: methods 1-4 and outer probe methods 1, 2: p < 0.0001; outer probe: p M2  = 0.0001), velocity (inner probe: p M1  < 0.0001, p M2  = 0.0155, p M3  = 0.0027; outer probe: p M1  < 0.0001, p M2  = 0.0045, p M3  = 0.0047, p M4  = 0.0037) and serosal flow (outer probe, methods 1 and 2: p < 0.0001; p M3  = 0.0009, p M4  = 0.0008). The histopathological analysis showed a significant association with time (p = 0.003) but not with the experimental method (p = 0.1386)., Conclusions: Intestinal diffusion is affected significantly by perfusion changes in mature minipigs. As shown by NMR-MOUSE monitoring, ischemia and flow reduction have contrary effects on intestinal diffusion and, additionally, the fast and slow diffusion components show opposite trends during each of those pathological perfusion states. Prior intraluminal glucose application seems to attenuate the effects of malperfusion on intestinal diffusion., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Preeclampsia (PE) is characterized by systemic maternal endothelial dysfunction. Changes in endothelial reactivity have been reported before the onset of clinical signs of PE, and continuing into the post-partum period. Women who smoke during pregnancy have a 33% reduced risk of developing PE. This reduced risk is hypothesized to be, in part, attributed to carbon monoxide (CO), a by-product of cigarette combustion and a known endogenous vasodilator. Determining the vascular effects of CO in healthy women, may inform how CO can improve endothelial function and have promise as a novel therapeutic for PE. As part of a pilot study to determine the vascular effects of CO, the aim of this study was to measure microvascular vasodilation following low-dose CO inhalation. Non-pregnant women inhaled ambient room air or 250 ppm CO for 24 min during microvascular assessment using laser speckle contrast imaging. Changes in vascular flux were measured in the forearm before, during, and following a three-minute arterial occlusion. CO inhalation increased end-tidal breath CO (EtCO) (9.1 ± 1.9 vs. 1.8 ± 0.7 ppm, p < 0.05) and increased microvascular vasodilation, measured as difference of maximum level/resting level ratio (mean difference 0.476, 95% confidence interval (CI) = 0.149-0.802 vs. 0.118, 95% CI = -0.425-0.662, p < 0.05). Women who inhaled CO had a longer time to half recovery of endothelial function following arterial occlusion, compared to controls (hazard ratio 0.29, 95% CI = 0.10-0.91, p = 0.033). Inhalation of CO moderately increased EtCO and resulted in an increased microvascular response, suggesting that CO may have potential as a therapeutic for PE., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Fluorescence-mediated photoplethysmography (FM-PPG) is the first routine clinical methodology by which to quantifiably measure tissue blood perfusion in absolute terms (mL blood/sec ∗ mm 2 tissue). The FM-PPG methodology has been described in detail previously in this journal (MVR 114, 2017, 92-100), along with initial proof-of-concept measurements of blood perfusion in both ocular and forearm skin tissues. The motivation for the current study was to investigate whether FM-PPG can be used readily and routinely under realistic clinical conditions. The vehicle for doing this was to measure medial foot capillary blood flow, i.e., tissue perfusion, in 7 normal subjects, mean = 6.76 ± 2.29 E-005 mL/(sec ∙ mm 2 ), and lesion-free areas of 8 type-2 diabetic patients with skin ulceration, mean = 4.67 + 3.15 E-005 mL/(sec ∙ mm 2 ). Thus, perfusion in the diabetics was found to be moderately lower than that in the normal control subjects. Earlier skin perfusion measurements in medial forearms of 4 normal subjects, mean = 2.64 + 0.22 E-005 mL/(sec ∙ mm 2 ), were lower than both the normal and diabetic foot perfusion measurements. Variability in the heartbeat-to-heartbeat blood perfusion pulses in the skin capillaries, defined as the ratio of the standard deviation among beat-to-beat pulses divided by the mean perfusion of those pulses, was determined for each subject. Average variability in foot skin was 21% in the diabetic population, versus 16% for normal subjects; and it was 18% in forearm skin. We conclude that absolute quantitative FM-PPG measurement of skin blood perfusion at the level of nutritive capillaries is feasible routinely under clinical conditions, allowing for quantitative measurement of skin tissue blood perfusion in absolute terms., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: To evaluate perfusion alterations in skeletal muscle in a canine hind limb ischemia model using color-coded digital subtraction angiography (CC-DSA)., Methods: Twelve beagles underwent embolization at the branch of their left deep femoral artery. Right hind limbs were used as the control group. Angiography was performed before and immediately after embolization. Upon CC-DSA analysis, time to peak (TTP) was measured before embolization in both sides of the beagles' hind limbs at the middle iliac artery, and the distant, middle and proximal femoral artery. Regions of interest (ROI) peak and ROI peak time were symmetrically computed in proximal and distal thigh muscles before and immediately after embolization. The data were analyzed and compared using the Wilcoxon signed rank test., Results: Before embolization, ROI peak in the proximal thigh was lower than in the ipsilateral distal thigh, whereas ROI peak time in the proximal thigh was longer than in the distal thigh. In the iliac femoral artery, there was no significant difference in ROI peak, ROI peak time, or TTP between right and left sides. After embolization, ROI peaks in proximal and distal skeletal muscles of the left hind limb were significantly lower than on the contralateral side. ROI peak time was significantly longer in the left proximal and left distal thigh compared to the contralateral side. There were no significant changes in ROI peak or ROI peak time in the right proximal and right distal thigh compared to pre-embolization values. Changes in ROI peak and ROI peak time were larger in the left proximal than in the left distal thigh., Conclusion: CC-DSA provided real-time measurement of changes in vascular hemodynamics and skeletal muscle perfusion without increasing X-ray usage or contrast agent dose., (Copyright © 2018. Published by Elsevier Inc.)

Objectives: Laser speckle contrast imaging (LSCI) has seen limited use in the study of perfusion dynamics such as vasomotion. The aim of this study was to investigate the effects of a prolonged seated position on perfusion dynamics in the nail bed using LSCI., Methods: Perfusion was recorded in digits II to IV bilaterally for 20 min during two separate sessions in ten healthy volunteers. The acclimatization period was 5 min for the 1st session and 20 min for the 2nd. Perfusion variability and the presence of recurring perfusion dips were analyzed. A digital nerve block was done to verify suspected nervous origin of phenomenon., Results: Synchronized phases of vasoconstriction were observed in all subjects with perfusion dips in all digits bilaterally and simultaneously. Application of a digital nerve block abolished perfusion dips. The frequency of this phenomenon increased by 25.0% (95% CI: 1.6 to 49.2%) in the left-hand digits after a prolonged seated position. Perfusion variability increased by 11.6% (95% CI: 2.6 to 20.3%) in the digits of the left hand. Perfusion changes in right-hand digits did not significantly increase. During the 1st session, temperature increased by 2.7 °C (1.1 to 4.2) while it decreased by 1.3 °C (0.2 to 2.4) during the 2nd session., Conclusion: The observed perfusion dips are of a centrally mediated nervous origin but are also affected by local factors. They are affected by seating duration and differ between left and right hands, likely because of local micro perfusion dips. This phenomenon seems related to digital thermoregulation., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Microvascular assessment has become increasingly used in gynecology to better understand the pathophysiology of various vulvar conditions and to study sexual function. Alteration in blood perfusion of the vulvar area has been observed using laser technologies in women with provoked vestibulodynia (PVD), the leading cause of vulvar pain. However, no studies have thus far investigated the reliability of and agreement between lasers for evaluating vulvar blood perfusion., Objectives: The main objective was to investigate the between-session reliability of the laser Doppler perfusion imaging (LDPI) and laser speckle contrast imaging (LSCI) for assessing blood perfusion of the vulvar vestibule in women with PVD. Secondary aims were to evaluate the association and agreement between the two laser technologies., Methods: Twenty-six women with PVD participated in the study. Blood perfusion of the vulvar vestibule was assessed with LDPI and LSCI during two sessions 2 to 4 weeks apart. Blood perfusion was analyzed in five specific areas of the vulvar vestibule: 1) 3 o'clock site, 2) 6 o'clock site, 3) 9 o'clock site, 4) central area (delimited by areas 1, 2 and 3), and 5) posterior fourchette. The reliability of the measurements of the two instruments was calculated with intraclass correlation coefficients (ICCs), standard errors of measurement (SEMs) and coefficients of variation (CVs). Paired t-tests were also computed to compare the CVs of each laser technology. The association and agreement between LDPI and LSCI measurements were evaluated by Pearson's correlation coefficients and Bland-Altman plots, respectively., Results: Excellent reliability was found for LDPI (ICCs = 0.78-0.80, p < 0.001, SEMs = 16.1-47.9) and LSCI measurements (ICCs = 0.75-0.81, p ≤ 0.001, SEMs = 17.0-52.2) for all vulvar vestibule areas. However, CVs were significantly higher using LDPI (CVs = 15.1-19.8) when compared to LSCI (CVs = 7.0-11.6) for all areas (p ≤ 0.031), except for area 4 (p = 0.079). Significant correlations were found between LDPI and LSCI for all areas (r = 0.58-0.89, p ≤ 0.003). Bland-Altman plots revealed a systematic difference between LDPI and LSCI measurements., Conclusion: Findings show that both LDPI and LSCI measurements are reliable for assessing blood perfusion of the vulvar vestibule in women with PVD. The LSCI appears to be a more reliable measurement as it presents less variation than LDPI. Finally, although LDPI and LSCI measurements are related, the systematic difference observed between them makes it impossible to compare absolute units., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: The time taken for epinephrine to achieve its optimal effect during local anesthesia has recently become the subject of debate. The time from injection to commencement of surgery is traditionally quoted to be 7 to 10 min, while recent reports claim that it may take 30 min to achieve maximum hypoperfusion, which would prolong the time required for surgical procedures. The discrepancy may be related to difficulties associated with the techniques used to measure blood perfusion. The aim of this study was to test two methods of determining the time to maximum hypoperfusion., Methods: Laser speckle contrast imaging (LSCI) and red, green, blue (RGB) analysis of images obtained with a commercial digital camera, were used to monitor the effect of infiltration with commonly used local anesthetic preparations: lidocaine (20 mg/ml) + epinephrine (12.5 μg/ml), lidocaine (10 mg/ml) + epinephrine (5 μg/ml), and lidocaine (20 mg/ml) alone, in healthy subjects., Results: LSCI showed a paradoxical increase in signal after the injection of local anesthetics containing epinephrine, probably due to a change in the laser penetration depth resulting from blanching of the skin. However, RGB analysis of digital photographs gave more reliable results, showing skin blanching that corresponded to the expected effect of epinephrine in local anesthetics. The time to maximum effect was found to be 7 (range 5-10) minutes for 12.5 μg/ml epinephrine, and 9 (range 7-13) minutes for 5 μg/ml epinephrine in lidocaine., Conclusions: RGB analysis of digital images proved to be a valid technique for monitoring the effect of local anesthetics with epinephrine in human skin. The technique requires only a commercial digital camera and constitutes a cheap, simple method. The optimal delay between epinephrine injection and incision, to minimize bleeding, was found to be 7 to 9 min, which is in good agreement with common surgical practice., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: It has been shown in many previous studies that there were significant changes of the brain anatomy and function in strabismus. However, the significance of the alterations of resting cerebral blood flow (CBF) in comitant exophoria (CE) remains obscure. Arterial spin labeling (ASL) MRI, which is a noninvasive method, could be applied to detect the cerebral blood flow quantitatively. Our study aimed to compare the resting CBF between the comitant exophoria and health controls using pseudo-continuous arterial spin labeling (pCASL) perfusion MRI method., Methods: 32 patients (25 males and 7 females) with CE (study group), and 32 (25 males and 7 females) healthy individuals with matched age and sex status (control group) underwent a whole-brain pCASL magnetic resonance (MR) examination at the resting state. The resting CBF were voxel-wise compared between the two groups using an analysis of variance designed in a statistical parametric mapping program. The CE patients were distinguishable from the healthy controls (HCs) by receiver operating characteristic (ROC) curves., Results: Compared with the control group, the CE group showed significantly increased resting CBF values in the right parahippocampal regions, bilateral medial frontal gyrus/anterior cingulate cortex, left inferior frontal gyrus, right inferior frontal gyrus, left superior frontal gyrus, bilateral medial cingulate cortex, right middle frontal gyrus, and right paracentral lobule., Conclusion: Comitant exophoria showed increased resting CBF in eye movement-related brain areas including supplementary eye field, cingulate eye field and frontal eye field, which could be an explanation of the brain function compensation for the ocular motility disorders in the CE patients., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: To evaluate endothelium-dependent microvascular reactivity during cardiopulmonary bypass (CPB) in surgery for the correction of cyanotic and acyanotic congenital heart disease (CHD) in children and infants using laser Doppler perfusion monitoring (LDPM)., Methods: This cross-sectional observational study included one hundred consecutive acyanotic (AC, n = 61) and cyanotic (C, n = 39) pediatric patients scheduled for cardiac surgery for correction of CHD. The endothelium-dependent microvascular vasodilation of the skin of the forehead was evaluated using a single-point LDPM coupled with local thermal hyperemia (LTH)., Results: LTH induced significant increases in microvascular conductance both in AC and C patients after the induction of anesthesia, during CPB and after weaning from CPB. Nevertheless, the vasodilation induced by LTH was significantly blunted during CPB when compared with values obtained after the induction of anesthesia both in AC and C patients. Microvascular endothelial reactivity nearly normalized after the discontinuation of CPB., Conclusion: The evaluation of systemic microvascular reactivity on the forehead skin of infants and children using LDPM appears to be a valuable tool for optimizing microvascular perfusion during CPB in pediatric cardiac surgery., (Copyright © 2018 Elsevier Inc. All rights reserved.)

This study was conducted to evaluate conjunctival blood flow velocities and microvascular network density in patients with dry eye disease (DED). Twenty-five patients with DED and 25 healthy controls were recruited. The microvasculature and microcirculation of the temporal bulbar conjunctiva of the right eyes were assessed using a functional slit-lamp biomicroscope. Vascular variables included blood flow velocity (BFV), blood flow rate (BFR), microvascular network density and vessel diameter. A fractal analysis was performed using the box counting method to measure the fractal dimension (Dbox) representing the vessel density. The bulbar BFV was 0.59 ± 0.09 mm/s in the DED group and 0.47 ± 0.12 in the control group (P < 0.001). BFR was 169.5 ± 1.8 in the DED group compared to the control group (107.2 ± 49.6) (P < 0.001). Dbox was higher in DED patients (1.65 ± 0.04) than controls (1.60 ± 0.07, P < 0.05). Moreover, the vessel diameter was larger in the DED group (21.8 ± 1.8 μm) compared with controls (17.9 ± 2.2 μm, P < 0.001). Dbox was positively related with ocular surface disease index (OSDI) in patients with DED (r = 0.54, P = 0.008). Microvascular alterations were found in the bulbar conjunctiva of DED patients, including increased blood flow velocity, higher vessel density and larger vessel diameter., (Copyright © 2018. Published by Elsevier Inc.)

Objective: To study blood flow, vascular volume and arterio-venous passages in induced mammary tumours of the rat to characterize parameters possibly responsible for tumour hyponutrition., Method: Dimethylbenzanthracene-induced mammary tumours in Sprague-Dawley rats were studied. Regional blood flow was studied by use of the radioactive microsphere tracer technique using 141 Cerium-labelled 15μm spheres coinjected into the left cardiac ventricle with 125 Iodine-labelled 25μm spheres. Blood volume was studied by use of 125 Iodine- or 99m Technetium-labelled human serum albumin, the latter allowing autoradiography of tumour sections for visualization of flow and volume., Results: Twenty-seven rats with 170 tumours had a mean tumour blood flow of 48 and 67mL×min -1 ×100g -1 using 15 and 25μm sphere data, respectively, indicating a significant passage through vessels between 15 and 25μm. The lungs showed a "nominal bronchial" blood flow of 260 and 135mL×min -1 ×100g -1 for the 15 and 25μm spheres, respectively, indicating pulmonary trapping, particularly of small spheres passing the systemic circulation in vessels larger than 15μm. There was a positive correlation between the total tumour blood flow within individual rats and trapped spheres of both dimensions in the lungs, indicating shunts also larger than 25μm. Normal tissues disclosed only small differences in regional blood flow as measured by the two spheres. Blood volume was studied in 20 rats with 120 tumours, with a vascular volume of 3.6mL×100g -1 representing a blood turnover >15 times/min. Blood volume co-localized with perfusion as seen in autoradiographs., Conclusion: In induced rat mammary tumours, a high fraction of blood, 28%, passes arterio-venous vessels between 15 and 25μm and there also exist passages >25μm. These findings indicate that the functional capacity of the tumour vascular bed might be impaired, adding to the abnormal microenvironment of tumours., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background/purpose: Objective, reliable and easy monitoring of microvascular tissue perfusion is a goal that was achieved for many years with limited success. Therefore, a new non-invasive hyperspectral camera system (TIVITA™) was tested for this purpose in an in vivo animal model., Methods: Evaluation of tissue oxygenation during ischemia and upon reperfusion was performed in left hind limb in a rat model (n=20). Ischemia was induced by clamping and dissection of the superficial femoral artery. Reperfusion of the limb was achieved by microsurgical anastomosis of the dissected artery. Oxygenation parameters of the hind limb were assessed via TIVITA™ before and immediately after clamping and dissection of the artery, 3 and 30min after reperfusion as well as on postoperative days 1 and 2. Thereby, the non-operated hind limb served as control. As clinical parameters, the refill of the anastomosis as well as the progress of the affected leg were assessed., Results: In 12 from 20 cases, TIVITA™ recorded a sufficient reperfusion with oxygenation parameters comparable to baseline or control condition. However, in 8 from 20 cases oxygenation was found impaired after reperfusion causing a re-assessment of the microvascular anastomosis. Thereby, technical problems like stenosis or local thrombosis were found in all cases and were surgically treated leading to an increased tissue oxygenation., Conclusions: The TIVITA™ camera system is a valid non-invasive tool to assess tissue perfusion after microvascular anastomosis. As it safely shows problems in oxygenation, it allows the clinician a determined revision of the site in time in order to prevent prolonged ischemia., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: To identify possible correlations between skin blood perfusion (BP) and dermal thickness (DT) in different skin areas of systemic sclerosis (SSc) patients., Methods: Sixty-two SSc patients, according to 2013 EULAR/ACR criteria, and 62 healthy subjects (CNT) were enrolled. Skin BP was analysed by laser speckle contrast analysis (LASCA) at the level of dorsum of the middle phalanx of the third fingers, dorsal aspect of the hands and zygoma. DT was assessed by both skin high frequency ultrasound (US) and modified Rodnan skin score (mRSS) in the same above reported areas. All patients were studied also by nailfold videocapillaroscopy (NVC) to assess the proper pattern of microvascular damage ("Early", "Active", or "Late")., Results: At the level of finger dorsum a statistically significant negative correlation was observed in SSc patients between skin BP and both ultrasound-DT (p=0.0005 r=0.43) and mRSS (p=0.0007 r=0.42), but not at the level of hand dorsum and zygoma. No statistically significant correlation was present between skin BP and ultrasound-DT at any level in CNT. In detail, SSc patients, compared to CNT, showed a statistically significant lower BP only at level of fingers (median PU 72.6 vs 136.1 respectively, p<0.0001) and a statistically significant higher ultrasound-DT at the level of dorsum of 3th finger bilaterally (median mm 0.9 vs 0.7, p<0.0001), dorsum of hands (median mm 0.9 vs 0.7, p<0.0001) and zygoma (median mm 0.8 vs 0.7, p<0.0001). A significant positive correlation between ultrasound-DT and mRSS was observed in SSc patients at level of the three areas (dorsum of fingers p<0.0001 r=0.51; dorsum of hands p=0.03 r=0.27; zygoma p=0.0001 r=0.45). A progressive decrease of skin BP and increase of ultrasound-DT was found correlated with the progression of the severity of NVC patterns., Conclusions: This study demonstrates for the first time in SSc patients a significant inverse relationship between skin BP, measured by LASCA, and DT, evaluated by both US and mRSS, at the level of dorsum of the middle phalanx of the third fingers., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Fluorescence-mediated photoplethysmography (FM-PPG) was developed to facilitate determination of tissue microvascular (capillary) blood perfusion, requiring intra-venous injection of a small bolus (~0.33mL) of dye (25mg/mL ICG) and acquisition of high-speed angiogram images (>15images/s). The methodology is applicable to microvascular capillary beds of tissues that can be optically imaged, directly or laparoscopically. Proof of concept of the methodology and feasibility of its implementation are demonstrated in human forearm skin and in the choroid of a monkey eye, determined to have blood perfusion rates on the order of 1e-5mL/(s·mm 2 ) and 10e-5mL/(s·mm 2 ), respectively. Ability to obtain absolute quantified tissue perfusion data ultimately can provide the means by which to characterize blood flow information at the nutritive capillary-vessel level in an objective and universally understood manner, in much the same sense that body temperature or blood pressure are., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose: Laser speckle contrast imaging (LSCI) continues to gain an increased interest in clinical and research studies to monitor microvascular perfusion. Due to its high spatial and temporal resolutions, LSCI may lead to a large amount of data. The analysis of such data, as well as the determination of the regions where the perfusion varies, can become a lengthy and tedious task. We propose here to analyze if a view-based temporal template method, the motion history image (MHI) algorithm, may be of use in detecting the perfusion variations locations., Methods: LSCI data recorded during three different kinds of perfusion variations are considered: (i) cerebral blood flow during spreading depolarization (SD) in a mouse; (ii) cerebral blood flow during SD in a rat; (iii) cerebral blood flow during cardiac arrest in a rat. Each of these recordings was processed with MHI., Results: We show that, for the three pathophysiological situations, MHI identifies the area in which perfusion evolves with time. The results are more easily obtained compared with a visual inspection of all of the frames constituting the recordings. MHI also has the advantage of relying on a rather simple algorithm., Conclusions: MHI can be tested in clinical and research studies to aid the user in perfusion analyses., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objectives: In patients with systemic sclerosis (SSc), fingertip digital ulcers (DUs) are believed to be ischaemic, and extensor surface DUs a result of mechanical factors/microtrauma. Our aim was to assess blood flow response to topical glyceryl trinitrate (GTN) compared to placebo in SSc DUs, looking for differences in pathophysiology between fingertip and extensor lesions., Method: This was a double-blind, randomised, crossover, placebo-controlled study. Sixteen (6 fingertip, 10 extensor) DUs were each studied twice (one day apart): once with GTN and once with placebo ointment. Perfusion at the DU centre ('DUCore') and periphery ('DUPeriphery'), as measured by laser Doppler imaging was performed before and immediately after ointment application, then every 10min, up to 90min post-application. We calculated the area under the response curve (AUC) and the ratio of peak perfusion to baseline, then compared these between GTN and placebo., Results: Perfusion was lower in the DUCore compared to the DUPeriphery (ratio of 0.52). The microvessels of the DUCore were responsive to GTN, with an increase in perfusion, with a similar effect in both fingertip and extensor DUs. The AUC and peak/baseline perfusion difference in means (ratio, 95% confidence interval) between GTN and placebo at the DUCore were 1.2 (1.0-1.6) and 1.2 (1.0-1.5) respectively, and at the DUPeriphery were 1.1 (0.8-1.6) and 1.0 (0.9-1.2) respectively., Conclusion: DUs (both fingertip and extensor) were responsive to topical GTN, with an increase in perfusion to the ischaemic DU centre. If both fingertip and extensor DUs have a (potentially reversible) ischaemic aetiology, this has important treatment implications., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Small nerve fibers regulate local skin blood flow in response to local thermal perturbations. Small nerve fiber function is difficult to assess with classical neurophysiological tests. In this study, a vasomotor response model in combination with a heating protocol was developed to quantitatively characterize the control mechanism of small nerve fibers in regulating skin blood flow in response to local thermal perturbation. The skin of healthy subjects' hand dorsum (n=8) was heated to 42°C with an infrared lamp, and then naturally cooled down. The distance between the lamp and the hand was set to three different levels in order to change the irradiation intensity on the skin and implement three different skin temperature rise rates (0.03°C/s, 0.02°C/s and 0.01°C/s). A laser Doppler imager (LDI) and a thermographic video camera recorded the temporal profile of the skin blood flow and the skin temperature, respectively. The relationship between the skin blood flow and the skin temperature was characterized by a vasomotor response model. The model fitted the skin blood flow response well with a variance accounted for (VAF) between 78% and 99%. The model parameters suggested a similar mechanism for the skin blood flow regulation with the thermal perturbations at 0.03°C/s and 0.02°C/s. But there was an accelerated skin vasoconstriction after a slow heating (0.01°C/s) (p-value<0.05). An attenuation of the skin vasodilation was also observed in four out of the seven subjects during the slow heating (0.01°C/s). Our method provides a promising way to quantitatively assess the function of small nerve fibers non-invasively and non-contact., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Previous work has demonstrated that spectral analysis is a useful tool to non-invasively ascertain the mechanisms of control of the cutaneous circulation. The majority of work using spectral analysis has focused on local control mechanisms, with none examining reflex control. Skin blood flow was analysed using spectral analysis on the dorsal aspect of the forearm of 7 males and 7 females during passive heat stress, with mean forearm and local temperature at the site of measurement maintained at thermoneutral (33°C) to minimize the effect of local control mechanisms. Participants were passively heated to ~1.2±0.1°C above baseline rectal temperature (d=4.0, P<0.001) using a water-perfused, tube lined suit, with skin blood flow assessed using a laser-Doppler probe with an integrated temperature monitor. Spectral analysis was performed using a Morlet wavelet on the entire data set, with median power extracted during 20min of data during baseline (normothermia) and hyperthermia. Passive heat stress significantly increased laser-Doppler flux above baseline (d=4.7, P<0.001). Spectral power of the endothelial nitric oxide-independent (0.005-0.01Hz; d=1.1, P=0.004), neurogenic (0.2-0.05Hz; d=0.6, P=0.025), myogenic (0.05-0.15Hz; d=1.5, P=0.002), respiratory (0.15-0.4Hz; d=1.4 P=0.002), and cardiac (0.4-2.0Hz; d=1.1, P=0.012) frequency intervals increased with passive heat stress. In contrast, the endothelial nitric oxide-dependent frequency interval did not change (0.01-0.02Hz; d=0.3, P=0.09) with passive heat stress. These data suggest that cutaneous reflex vasodilatation is neurogenic in origin and not mediated by endothelial-nitric oxide synthase, and are congruent with invasive examinations of reflex cutaneous vasodilatation., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: This study compares the effectiveness of a neuromuscular electrical stimulation (NMES) device and an intermittent pneumatic compression (IPC) device on enhancing microcirculatory blood flow in the thigh of healthy individuals, when stimulation is carried out peripherally at the calf., Materials and Methods: Blood microcirculation of ten healthy individuals was recorded using laser speckle contrast imaging (LSCI) technique. A region of interest (ROI) was marked on each participant thigh. The mean flux within the ROI was calculated at four states: rest, NMES device with visible muscle actuation (VMA), NMES device with no visible muscle actuation (NVMA) and IPC device., Results: Both NMES and IPC devices increased blood flow in the thigh when stimulation was carried out peripherally at the calf. The NMES device increased mean blood perfusion from baseline by 399.8% at the VMA state and 150.6% at the NVMA state, IPC device increased the mean blood perfusion by 117.3% from baseline., Conclusion: The NMES device at VMA state increased microcirculation by more than a factor of 3 in contrast to the IPC device. Even at the NVMA state, the NMES device increased blood flow by 23% more than the IPC device. Given the association between increased microcirculation and reduced oedema, NMES may be a more effective modality than IPC at reducing oedema, therefore further research is needed to explore this., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Systemic sclerosis (SSc) patients are at high risk for the development of ischemic digital ulcers (DUs). The aim of this study was to assess in SSc patients a correlation between skin perfusion evaluated by LDPI and DUs and to evaluate the prognostic value of skin perfusion to predict the new DUs occurrence. Fifty eight (47 female, 11 male) SSc patients were enrolled. Skin perfusion of hands and region of interest (ROIs) was measured by Laser Doppler perfusion Imager (LDPI). The proximal-distal gradient (PDG) was present when the perfusion mean difference between ROI1 and ROI2 was >30 pU. The skin perfusion of hands is lower in SSc patients than in healthy controls. The skin perfusion decreased with severity of capillaroscopic damage. Both mean perfusion of hand and PDG are significantly (p<0.01 and p<0.0001, respectively) lower in SSc patients with new DUs than in SSc patients without DUs. Only 2 of 11 SSc patients (18.2%) with PDG developed new digital ulcers, conversely 36 of 47 (76.6%) SSc patients without PDG developed new digital ulcers (p<0.001). The ROC curves demonstrated a good accuracy of new DUs prediction for PDG (0.78, p<0.0001). Using this cut-off value of 30 pU, RR for new DUs development in SSc patients without PDG is 4,2 (p<0.001). LDPI indices could be used in association to the capillaroscopic and clinical findings or serological tests in the identification of patients at high risk of developing DUs., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: Portal hyperperfusion after extended hepatectomy or small-for-size liver transplantation may induce organ dysfunction and failure. This study was designed to monitor and characterize the hepatic microcirculatory perfusion following different volumes of hepatectomy in rats by using laser speckle contrast image (LSCI) and Oxygen to See (O2C), a spectrometric device., Methods: The microcirculatory liver blood flow of the rats that underwent 68%, 85% and 90% hepatectomy (68PH, 85PH and 90PH) was monitored with LSCI and O2C before and following the hepatectomy. The portal venous flow (PVF) and hepatic arterial flow (HAF) were measured with an ultrasonic flowmeter. Liver regeneration, liver injury, histologic evaluation and gene expression were also assessed at 12h, 24h, 3d and 7d post hepatectomy., Results: All the 68PH and 85PH rats survived, and 57% of the 90PH rats survived. After hepatectomy, both PVF and HAF decreased transiently, with the PVF of the 85PH and 90PH rats significantly lower than that of the 68PH rats. In contrast, the PVF and HAF per gram of liver weight were greatly increased after liver resection and were proportional to the volume of resected liver. Correspondingly, the microcirculatory liver blood flow of the 68PH, 85PH and 90PH rats, as assessed by both LSCI and O2C, were increased after hepatectomy, and the 90PH group was significantly higher than the 68PH and 85PH groups. The hyperperfusion continued for approximately 3days and returned to baseline following the completion of liver regeneration. The liver venous oxygen saturation of the three groups decreased immediately after hepatectomy and returned to baseline from 24h after hepatectomy. The 90PH rats also showed delayed liver regeneration and the most severe liver injury, as reflected by increased serum ALT, AST and TBIL levels, hepatocellular vacuolization, and inflammatory and endothelial constriction gene expressions (TNF-α, IL-1β, MIP-1α, ET-1 and TM-1)., Conclusion: Hepatic microcirculation hyperperfusion resulting from major and extended liver resection could be assessed by LSCI and O2C methods. The 90PH in rats led to extraordinary sinusoidal hyperperfusion, severe endothelial injury and liver failure. Monitoring the changes of hepatic microcirculation perfusion following extended hepatectomy or small-for-size liver transplantation may help to analyze the extent of hyperperfusion., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background and Aim: Although femoral artery ligation-induced ischemia is commonly used in C57BL/6 or Balb/c mice, direct comparisons between femoral artery/vein (FAV) versus femoral artery (FA) excisions have not been reported. The goal of the present study is to investigate the effects of FAV versus FA excisions on hindlimb models using adult CD-1 mice., Methods: Two groups (n=10/group) of adult, mixed gender CD-1 mice were used to generate hindlimb ischemic models by excising either the FAV or FA. Laser Doppler Imaging was used to evaluate blood flow before surgery, immediately after surgery (Day 0), and then on Days 14 and 28. Toe necrosis was checked every 14days while skeletal muscle cellular remodeling and vascular networks were analyzed at the end of the experiment using pathohistological, Dil-vessel painting, and immunohistochemical approaches., Results: During the 4-week period, no statistical differences were found between FAV and FA excision-induced ischemia in terms of reduction of limb blood flow, paw size, number of necrotic toes, or skeletal muscle cell sizes. However, significant increases in centrally-located nuclei cells, adipose cells, diameters of Dil-stained arterioles, and CD31 + capillary densities, but decreases in arteriole densities/lengths were observed in ischemic limbs of both FAV and FA groups compared to control limbs., Conclusion: We conclude that FAV and FA excision in CD-1 mice generate a comparable degree of hindlimb ischemia, suggesting that, as expected, FAV is no more severe than FA. These findings may provide important information for researchers when selecting ligation methods for their hindlimb models., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Laser speckle contrast imaging (LSCI) is a real-time imaging modality reflecting microvascular perfusion. We report on the application of the motion history image (MHI) method on LSCI data obtained from the two hemispheres of a mouse. Through the generation of a single image, MHI stresses the microvascular perfusion changes. Our experimental results performed during a pinprick-triggered spreading depolarization demonstrate the effectiveness of MHI: MHI allows the visualization of perfusion changes without loss of resolution and definition. Moreover, MHI provides close results to the ones given by the generalized differences (GD) algorithm. However, MHI has the advantage of giving information on the temporal evolution of the perfusion variations, which GD does not., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objectives: Dynamic optical coherence tomography (D-OCT) is an angiographic variation of OCT that non-invasively provides images of the in vivo microvasculature of the skin by combining conventional OCT images with flow data. The objective of this study was to investigate and report on the D-OCT technique for imaging of the vascular networks in skin as well as to validate the method by comparing the results against already accepted blood flow measuring tools., Methods: 35 healthy subjects were recruited for the multicentre study, consisting of three experiments set up to examine the vascular blood perfusion during different induced physiologic changes in the blood flow. In order to validate the D-OCT images against existing techniques for blood flow measuring we performed consecutive D-OCT, chromametry and laser speckle contrast imager (LSCI) measurements on identical skin sites in all of the experiments. Blinded observer evaluations were performed in order to evaluate the vascular morphology in the D-OCT images., Results: The results showed a statistically significant positive correlation between the D-OCT measurements and the LCSI flux measurements (rs=0.494; 95% CI [0.357, 0.615]; p<0.001), and also the redness a* measurements were positively correlated with the D-OCT measurements (r=0.48; 95% CI [0.406, 0.55]). D-OCT was able to reliably image and identify morphologic changes in the vascular network consistent with the induced physiological changes of blood flow., Conclusion: This study has initiated validation of the use of D-OCT for imaging of skin blood flow. Our results showed that D-OCT was able to reliably image and identify changes in the skin vasculature consistent with the induced physiological blood flow changes. These basic findings support the use of D-OCT imaging for in vivo microcirculation imaging of the skin., (Copyright © 2016 Elsevier Inc. All rights reserved.)

In this work, we report about q statistics concept to improve the performance of generalized differences algorithm based on intensity histogram for imaging functional blood vessel structures in a rodent window chamber of a mice. The method uses the dynamic speckle signals obtained by transilluminating the rodent window chamber to create activity maps of vasculatures. The proposed method of generalized differences with q statistics (GDq) is very sensitive to the values of defined parameters such as: camera exposure time, the q value and the camera frame number. Appropriate choice of q values enhances the visibility (contrast) of functional blood vessels but at the same time without sacrificing the spatial resolution, which is of utmost importance for in-vivo vascular imaging., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Laser speckle contrast imaging (LSCI) provides a noninvasive and cost effective solution for in vivo monitoring of blood flow. So far, most of the researches consider changes in speckle pattern (i.e. correlation time of speckle intensity fluctuation), account for relative change in blood flow during abnormal conditions. This paper introduces an application of LSCI for monitoring wound progression and characterization of cutaneous wound regions on mice model. Speckle images are captured on a tumor wound region at mice leg in periodic interval. Initially, raw speckle images are converted to their corresponding contrast images. Functional characterization begins with first segmenting the affected area using k-means clustering, taking wavelet energies in a local region as feature set. In the next stage, different regions in wound bed are clustered based on progressive and non-progressive nature of tissue properties. Changes in contrast due to heterogeneity in tissue structure and functionality are modeled using LSCI speckle statistics. Final characterization is achieved through supervised learning of these speckle statistics using support vector machine. On cross evaluation with mice model experiment, the proposed approach classifies the progressive and non-progressive wound regions with an average sensitivity of 96.18%, 97.62% and average specificity of 97.24%, 96.42% respectively. The clinical information yield with this approach is validated with the conventional immunohistochemistry result of wound to justify the ability of LSCI for in vivo, noninvasive and periodic assessment of wounds., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Intense pulsed light (IPL) with low energy insufficient to completely destroy a vasculature was applied to rabbit ears to investigate vasculature alteration. Glycerol was combined with IPL to enhance the transfer efficacy of IPL energy. Both trans-illumination and laser speckle contrast images were obtained and analyzed after treatment. The application of IPL and glycerol combination induced vasodilation and improvement in blood flow. Moreover, such phenomenon was maintained over time. IPL may be applied to treat blood circulatory diseases by inducing vasodilation and to improve blood flow., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objectives: To correlate blood perfusion (BP) values assessed by laser speckle contrast analysis (LASCA) in selected skin areas of hands and face with nailfold capillary damage scores in systemic sclerosis (SSc) patients., Methods: Seventy SSc patients (mean SSc duration 6 ± 5 years) and 70 volunteer healthy subjects were enrolled after informed consent. LASCA was performed at different areas of the face (forehead, tip of nose, zygomas and perioral region) and at dorsal and volar regions of hands. Microvascular damage was assessed and scored by nailfold videocapillaroscopy (NVC) and the microangiopathy evolution score (MES) was calculated., Results: SSc patients showed a significantly lower BP than healthy subjects at fingertips, periungual areas and palm of hands (p<0.0001), but not at the level of face and dorsum of hands. A gradual decrease of BP at fingertips, periungual and palm areas, was found in SSc patients with progressive severity of NVC patterns of microangiopathy ("early", "active", or "late") (p<0.01). A negative correlation was observed between MES and BP values, as well as between loss of capillaries and BP, at the same areas (p<0.001 and p<0.01, respectively). Patients with diffuse cutaneous SSc (dcSSc) showed lower BP than those with limited cutaneous SSc (p<0.04)., Conclusions: LASCA detects a significant reduction of BP only in those areas usually affected by Raynaud's phenomenon (fingertips, periungual and palm areas), especially in dcSSc patients, and BP values significantly correlate with the nailfold capillaroscopy scores of microangiopathy., (Copyright © 2016. Published by Elsevier Inc.)

Particle skimming is a phenomenon where particles suspended in fluid flowing through vessels distribute disproportionately to bulk fluid volume at junctions. Microspheres are considered a gold standard of intra-organ perfusion measurements and are used widely in studies of flow distribution and quantification. It has previously been hypothesised that skimming at arterial junctions is responsible for a systematic over-estimation of myocardial perfusion from microspheres at the subendocardium. Our objective is to integrate coronary arterial structure and microsphere distribution, imaged at high resolution, to test the hypothesis of microsphere skimming in a porcine left coronary arterial (LCA) network. A detailed network was reconstructed from cryomicrotome imaging data and a Poiseuille flow model was used to simulate flow. A statistical approach using Clopper-Pearson confidence intervals was applied to determine the prevalence of skimming at bifurcations in the LCA. Results reveal that microsphere skimming is most prevalent at bifurcations in the larger coronary arteries, namely the epicardial and transmural arteries. Bifurcations at which skimming was identified have significantly more asymmetric branching parameters. This finding suggests that when using thin transmural segments to quantify flow from microspheres, a skimming-related deposition bias may result in underestimation of perfusion in the subepicardium, and overestimation in the subendocardium., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: Laser speckle contrast imaging (LSCI) is a novel technique for microcirculation imaging not previously used in the liver. The aim of the present experimental study was to evaluate the use of LSCI for assessing liver microcirculation., Materials and Methods: In six male Wistar rats, the median liver lobe was exposed through a midline laparotomy. Liver blood perfusion was measured simultaneously with LSCI and sidestream dark-field (SDF) imaging at baseline and during sequential temporary occlusions of the portal vein, hepatic artery, and total blood inflow occlusion. Both the inter-individual variability associated with perfusion sampling area and comparisons in perfusion measurements between both imaging techniques were investigated and validated for the application of LSCI in the liver., Results: Occlusion of the hepatic artery, portal vein, and total inflow occlusion resulted in a significant decrease in LSCI signal to 74.7±6.4%, 15.0±2.3%, and 10.4±0.5% respectively (p<0.005 vs. baseline). The LSCI perfusion units correlated with sinusoidal blood flow velocity as measured with SDF imaging (Pearson's r=0.94, p<0.001). In a 10 mm diameter region of interest, as measured with LSCI, baseline inter-individual variability measured by the coefficient of variability was 13%., Conclusion: Alterations in LSCI signal during sequential inflow occlusions were in accordance with previously published results on hepatic hemodynamics in the rat and correlated well with our SDF imaging-derived sinusoidal blood flow velocity measurements. We found that LSCI was able to produce reproducible real-time blood perfusion measurements of hepatic microcirculation. Compared to established techniques for liver blood perfusion measurements LSCI holds the advantages of non-contact measurements over large surfaces with a high speed of data acquisition., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Objective: To assess morphology and blood flow of the proper palmar digital arteries (PPDA) by color Doppler ultrasonography (CDUS) and its relationship with nailfold videocapillaroscopy (NVC), skin blood perfusion and digital arteries pulsatility of hands in SSc patients and healthy controls., Methods: CDUS, NVC, laser Doppler perfusion imaging (LDPI) and photoplethysmography (PPG) were performed in 36 systemic sclerosis (SSc) patients and 20 healthy controls., Results: CDUS was pathologic in 69% of patients with SSc and in none of healthy controls (p<0.0001). SSc patients with low vascular damage (early capillaroscopic pattern) have a normal morphology of PPDA, but the blood flow, evaluated by peak systolic velocity (PSV) and end diastolic velocity (EDV), is reduced and vascular resistance, measured by resistive index (RI) and pulsatility index (PI), increased. At this stage the LDPI mean perfusion and digital artery pulsatility, evaluated by PPG, were reduced. The US changes appear with microvascular damage progression (active and late capillaroscopic patterns), while the PPDA blood flow progressively decreases (PSV and EDV decreased, RI and PI increased). The macrovascular damage correlates with disease duration. Anti-topoisomerase I represents an independent predictive factor for macrovascular damage. We not observed any association between digital ulcer history, pulmonary fibrosis and US findings., Conclusion: PPDA blood flow dysfunction is already present in early disease. Structural macrovascular damage progresses with worsening of SSc microangiopathy., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objective: To compare the inter-day reproducibility of post-occlusive reactive hyperaemia (PORH) and sympathetic vasomotor reflexes assessed by single-point laser Doppler flowmetry (SP-LDF), integrating-probe LDF (IP-LDF) and laser speckle contrast imaging (LSCI), and the spatial variability of PORH assessed by IP-LDF and LSCI. We also evaluated the relationship between IP-LDF and LSCI perfusion values across a broad range of skin blood flows., Methods: Eighteen healthy adults (50% male, age 27 ± 4 years) participated in this study. Using SP-LDF, IP-LDF and LSCI, indices of skin blood flow were measured on the forearm during PORH (1-, 5- and 10-min occlusions) and on the finger pad during inspiratory gasp and cold pressor tests. These tests were repeated 3-7 days later. Data were converted to cutaneous vascular conductance (CVC; laser Doppler flow/mean arterial pressure) and expressed as absolute and relative changes from pre-stimulus CVC (ΔCVC(ABS) and ΔCVC(REL), respectively), as well as normalised to peak CVC for the PORH tests. Reproducibility was expressed as within-subjects coefficients of variation (CV, in %) and intraclass correlation coefficients., Results: The reproducibility of PORH on the forearm was poorer when assessed with SP-LDF and IP-LDF compared to LSCI (e.g., CV for 5-min PORH ΔCVC(ABS)=35%, 27% and 19%, respectively), with no superior method of data expression. In contrast, the reproducibility of the inspiratory gasp and cold pressor test responses on the finger pad were better with SP-LDF and IP-LDF compared to LSCI (e.g., CV for inspiratory gasp ΔCVC(REL)=13%, 7% and 19%, respectively). The spatial variability of PORH responses was poorer with IP-LDF compared to LSCI (e.g., CV ranging 11-35% versus 3-16%, respectively). The association between simultaneous LSCI and IP-LDF perfusion values was non-linear., Conclusion: The reproducibility of cutaneous PORH was better when assessed with LSCI compared to SP-LDF and IP-LDF; probably due to measuring larger skin areas (lower inter-site variability). However, when measuring sympathetic vasomotor reflexes on the finger pad, reproducibility was better with SP-LDF and IP-LDF, perhaps due to the high sensitivity of LSCI to changes in skin blood flow at low levels., (Copyright © 2011 Elsevier Inc. All rights reserved.)

It is crucial to monitor spatio-temporal changes in the microcirculation of flaps. A laser speckle imaging technique based on speckle contrast analysis compensates for disadvantages and can assess regional blood flow distribution at high resolution. In this paper, temporal changes in circulation were investigated with full-field laser perfusion imaging (FLPI) in rat dorsal delay random flaps. Twenty Sprague-Dawley rats were randomized into two groups (delay procedures and controls) with a standardized dorsal random pattern flap (caudally based, 3 × 10 cm). Blood flow dynamics in both groups were studied with FLPI at different timepoints, and the size of the surviving and necrotic areas of the flaps, vessel distribution, microvessel density and vessel diameters were appraised. The results showed that blood flow after secondary elevation of the flap did not rapidly decrease in the delay group compared to the control group. Viability of the skin flaps, vessel diameter, and micro-vessel density was significantly improved in the delay group. Delay procedure work by diminishing the resistance to blood flow of the flap with FLPI real-time detection, and laser speckle imaging could be a better method for studying microcirculation and judging flap vascularity., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Quantitative measurement of functional tissue perfusion is essential for early diagnosis and proper treatment of peripheral arterial occlusive disease (PAOD). We have previously demonstrated that dynamic imaging of near-infrared fluorophore indocyanine green (ICG) can be a noninvasive and sensitive tool to measure tissue perfusion. In the present study, we investigated the clinical efficacy of ICG perfusion imaging method for the diagnosis of PAOD. Total nineteen PAOD patients and age-matched controls (n=10) were evaluated for lower extremity tissue perfusion using ICG perfusion imaging. The perfusion rates of the lower extremities with severe PAOD (n=25 legs, 16.6±8.3%/min) were significantly lower than those of normal controls (38.1±17.3%/min, p<0.001). In cases of mild PAOD, the perfusion rates (n=11 legs, 18.3±10.3%/min) were also significantly lower compared to the control; while the conventional ankle-brachial index (ABI) test failed to detect mild functional impairment. These results collectively indicate that ICG perfusion imaging can be a very effective tool for diagnosis of PAOD with a superior efficacy in comparison to conventional ABI test., (Copyright © 2010 Elsevier Inc. All rights reserved.)

When one is studying the physiology of the cutaneous microcirculation there is a need for relevant non-invasive and versatile techniques. In this study we used a new optical device, the tissue viability imager (TiVi), to map changes in cutaneous microvascular concentrations of red blood cells during iontophoresis of vasoactive substances (noradrenaline (NA) and phenylephrine (Phe) for vasoconstriction and acetylcholine (ACh) and sodium nitroprusside (SNP) for vasodilatation). We aimed to present data both individually and pooled, using a four-variable logistic dose response model that is commonly used in similar in vitro vascular studies. The accuracy of the TiVi was also investigated by calculating the coefficient of variation and comparing it with similar tests previously done using laser Doppler imaging. Tests were also performed using the TiVi and LDPI simultaneously to further compare the two methods. Results showed that the TiVi is capable of quantifying vascular responses to iontophorised noradrenaline and phenylephrine without the need to increase background flow first. Fitting the TiVi data to the dose response model resulted in ED(50)-values with narrow confidence intervals and acceptable r(2) values. Mean ED(50)-values for the TiVi did not differ significantly from similar values obtained using laser Doppler. Results further seem to suggest that when the blood perfusion increases during vasodilatation in skin the initial phase relies mainly on an increase in red blood cell concentration whereas the further perfusion increase is due to an increase in red blood cell velocity.