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Segmentation of the Optic Nerve Head Based on Deep Learning to Determine its Hemoglobin Content in Normal and Glaucomatous Subjects
摘要： Objective: To determine the limits of the optic nerve head (ONH) in color fundus images using Deep learning (DL) for the estimation of its hemoglobin topographic distribution. Also, to evaluate the usefulness of that distribution in glaucoma diagnosis singly or in association with perimetry. Methods: A DL method was trained using 40000 fundus images and applied to 89 normal eyes and 77 confirmed or suspect glaucomas. DL and manual segmentation were compared. The eyes were also examined once with TOP perimetry (Octopus 300) and Spectralis-OCT and twice with Cirrus-OCT and Laguna ONhE, a program which estimates hemoglobin from color photographs, using improved criteria from previous studies. Results: The Sorensen-Dice similarity index between manual and automatic segmentations was 0.993. Intra-class correlation coefficients were similar when comparing the results of the Laguna ONhE indices using the manual and automatic segmentations (confidence intervals: 0.933-0.978). For specificity close to 95%, the GDF index, a factor that measures the distribution of hemoglobin at the nerve, obtained sensitivities between 70.1 and 74.0% (manual vs. automatic segmentations). The retinal nerve fiber layer thickness (RNFLT) of both OCTs provided sensitivities between 67.1 and 68.8% and the BMO-RMW of Spectralis-OCT 69.7%. Associating several normalized indices, e.g. a new visual field harmony index (Threshold Coefficient of Variation, TCV) and GDF, provided 85.7% sensitivity for 97.8% specificity. GDF correlation with Spectralis-OCT BMO-RMW index was similar to that obtained between this index and the RNFLT of the same instrument. For 95% specificity, the diagnostic concordance (kappa value) between both Spectralis-OCT indices was 0.694 and between its BMO-RMW and Laguna ONhE GDF 0.804-0.828. Conclusion: A fully automatic delimitation of the optic nerve head allows the correct, reproducible and efficient use of the Laguna ONhE method, and its effectiveness is greatly increased if associated with a perimetric harmony index.
关键词： Glaucoma,Visual field,Hemoglobin,Perfusion,Morphology,Perimetry,Optic nerve head
更新于2025-09-19 17:15:36
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Comparison of Neurovascular Coupling between Normal Tension Glaucoma Patients and Healthy Individuals with Laser Speckle Flowgraphy
摘要： Background The purpose of this pilot study was to investigate the differences in neurovascular coupling between Caucasian patients with normal tension glaucoma (NTG) and healthy subjects (HS) with Laser Speckle Flowgraphy (LSFG). Methods Measurement of optic nerve head blood flow was performed with LSFG. Mean blur rate of the whole optic nerve head (MA), of the big retinal vessels (MV) and of the microvasculature (MT) was analysed during continuous flicker light stimulation for four minutes. Results We included 12 eyes from 12 Caucasian patients with diagnosis of normal tension glaucoma and 12 eyes from 12 age- and sex-matched healthy individuals. MA, MV and MT all increased significantly in both groups during the observation period with no difference between the groups. Conclusion Neurovascular coupling is detectable in NTG patients. Flicker light stimulation leads to a comparable increase in ocular blood flow in glaucoma patients and healthy individuals.
关键词： flicker,laser speckle flowgraphy,ocular perfusion,normal tension glaucoma,neurovascular coupling
更新于2025-09-19 17:13:59
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Assessment of tissue perfusion and vascular function in mice by scanning laser Doppler perfusion imaging
摘要： Post-occlusive reactive hyperemia (PORH) is a key feature of physiological vasomotion to appropriately match the supply/demand ratio of tissues. This adaptive mechanism is severely disturbed in endothelial dysfunction with a reduced flow-mediated dilation (FMD). Reduced PORH and FMD are powerful prognostic risk factors in cardiovascular disease. While these parameters are frequently determined in human beings, comparable methods applicable to mouse models are sparse. We aimed to evaluate the applicability and accuracy of scanning laser Doppler perfusion imaging (LDPI) to measure PORH in the mouse hindlimb. Changes in mean perfusion in response to vasoactive drugs and PORH (assessed by scanning LDPI) were compared with changes in diameter and blood flow in the femoral artery, as assessed by high-resolution ultrasound. We found that the measured LDPI signal significantly correlated with changes of inflow into the femoral artery. Vasodilation induced by administration of nitroglycerine and acetylcholine increased vessel diameter, blood flow and mean perfusion, while vasoconstriction following administration of epinephrine decreased all three parameters. PORH was induced by temporal occlusion of the femoral artery with an external cuff. During occlusion, mean perfusion decreased to a condition of zero-perfusion and release of the cuff induced an immediate increase in blood flow that was followed by femoral artery dilation driving PORH/ perfusion. Surgical removal of the femoral artery decreased mean perfusion to a zero-perfusion level and fully abolished PORH. Importantly, the measurement of the PORH response by scanning LDPI is highly reproducible as determined by repeated measurements and intra/interobserver variation analysis. Last, we found that the PORH response was dependent on nitric oxide synthase and cyclooxygenase and declined with age. Thus, we here provide novel and robust non-invasive methods to serially measure tissue perfusion at baseline and during physiological and pharmacological modulation of vasomotor tone in the hindlimb of mice. The application of these LDPI scanning and ultrasound-based methods may be useful for testing the effects of drugs affecting vasomotor function or future elucidation of mechanisms leading to vasomotor dysfunction in mice in vivo.
关键词： age-dependent endothelial dysfunction,Laser Doppler perfusion imaging,nitric oxide synthase,hindlimb,reactive hyperemia
更新于2025-09-19 17:13:59
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Laser Doppler blood flowmeter as a useful instrument for the early detection of lower extremity peripheral arterial disease in hemodialysis patients: an observational study
摘要： Background: A simpler method for detecting atherosclerosis obliterans is required in the clinical setting. Laser Doppler flowmetry (LDF) is easy to perform and can accurately detect deterioration in skin perfusion. We performed LDF for hemodialysis patients to determine the correlations between blood flow in the lower limbs and peripheral arterial disease (PAD). Methods: This retrospective study included 128 hemodialysis patients. Patients were categorized into the non-PAD group (n = 106) and PAD group (n = 22), 14 early stage PAD patients were included in the PAD group. We conducted LDF for the plantar area and dorsal area of the foot and examined skin perfusion pressure (SPP) during dialysis. Results: SPP-Dorsal Area values were 82.1 ± 22.0 mmHg in the non-PAD, and 59.1 ± 20.3 mmHg in PAD group, respectively (p < 0.05). The LDF-Plantar blood flow (Qb) values were 32.7 ± 15.5 mL/min in non-PAD group and 21.5 ± 11.3 mL/min in PAD group (p < 0.001). A total of 21 non-PAD patients underwent LDF before and during dialysis. The LDF-Plantar-Qb values were 36.5 ± 17.6 mL/min before dialysis and 29.6 ± 17.7 mL/min after dialysis (p < 0.05). We adjusted SPP and LDF for PAD using logistic regression, SPP-Dorsal-Area and LDF-P were significantly correlated with PAD (p < 0.05). The receiver-operating characteristic curve analysis indicated cut-off values of 20.0 mL/min for LDF-Plantar-Qb during dialysis. Conclusion: LDF is a simple technique for sensitive detection of early-stage PAD. This assessment will help physicians identify early-stage PAD, including Fontaine stage II in clinical practice, thereby allowing prompt treatment.
关键词： Skin perfusion pressure,Peripheral arterial disease,Laser doppler flowmetry
更新于2025-09-16 10:30:52
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Minimally invasive laser Doppler flowmetry is suitable for serial bone perfusion measurements in mice
摘要： In vivo laser Doppler flowmetry (LDF) has previously been used to quantify blood perfusion accurately at a single timepoint in the murine tibial metaphysis. However, this procedure entailed substantial disruption to soft tissues overlying the bone and caused notable localized inflammation for several weeks after the procedure, impeding serial measurements in the same mouse. In this study, we tested a less invasive technique to measure perfusion in the tibia with LDF and determined that it can be used serially in the same mouse without causing signs of inflammation or gait perturbations. Twenty 14-week-old C57Bl/6J mice were evenly divided into groups that either had daily treadmill exercise or remained sedentary. Within these activity groups, mice were evenly subdivided into groups that received LDF measurements either weekly or only once at the study endpoint. Bone perfusion was measured with LDF in the anteromedial region of the right tibial metaphysis. Serum concentrations of interleukin 6, incision site wound area, and interlimb coordination during gait were measured weekly for four weeks. Tibial perfusion did not differ significantly between exercise and sedentary groups within the weekly or endpoint-only LDF groups at any timepoint. Perfusion was significantly increased in the third week in the weekly LDF group relative to measurements in the second and fourth weeks. Ligation of the femoral artery caused consistent, rapid reductions in tibial perfusion, validating that LDF is sensitive to changes in tibial blood supply. Weekly LDF procedures did not adversely affect gait, as interlimb coordination during treadmill locomotion was similar between weekly and endpoint-only LDF groups at every timepoint. Images of the incision site show wound closure within one week, and serum concentrations of interleukin 6 were not significantly different between weekly and endpoint-only groups. Together, these findings demonstrate that our minimally invasive LDF technique is suitable for serial in vivo measurements of intraosseous blood perfusion without inducing localized inflammation or negatively affecting gait patterns in mice.
关键词： Laser Doppler flowmetry,Vascular supply,Serial measurement,In vivo,Bone blood perfusion,Minimally invasive
更新于2025-09-16 10:30:52
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Perfusion dynamics of the medial sural artery perforator (MSAP) flap in lower extremity reconstruction using laser Doppler perfusion imaging (LDPI): a clinical study
摘要： Perforator flaps are a mainstay in reconstructive surgical practice but are limited by complications, including flap failure, resulting from flap hypoperfusion. This study aimed to characterize the early post-operative perfusion dynamics of the medial sural artery perforator flap in lower extremity reconstruction using laser Doppler perfusion imaging (LDPI). 12 patients, recruited between 2014 and 2015, with lower extremity reconstructions using free MSAP flaps were assessed for perfusion using a hand-held colour Doppler ultrasound device on days 1, 3, and 5 post-operatively. Perfusion at four distinct zones was assessed; whole flap, control zone, perforator zone, and distal zone, by a single operator using a standardized technique. The perforator zone was noted to have the highest relative perfusion of all zones measured across all post-operative days, and this was correlated with whole flap perfusion (r ? 0.82, p ? 0.002). No significant perfusion differences were found within any of the zones over the 5-day period. The perfusion at the distal zone was not found to correlate with either the perforator zone perfusion, flap length, flap length to width ratio or smoking status (p > 0.05). Perfusion of the MSAP flap can adequately be monitored using LDPI at any point throughout the flap, though is highest at the perforator zone, and remains constant in the early post-operative period.
关键词： medial sural artery perforator flap,Laser Doppler perfusion imaging,perfusion zones,perforators
更新于2025-09-12 10:27:22
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Impact of Knowledge-Based Iterative Model Reconstruction on Image Quality and Hemodynamic Parameters in Dynamic Myocardial Computed Tomography Perfusion Using Low-Tube-Voltage Scan
摘要： Objective: Knowledge-based iterative model reconstruction (IMR) yields diagnostically acceptable image quality in low-dose static computed tomography (CT). We aimed to evaluate the feasibility of IMR in dynamic myocardial computed tomography perfusion (CTP). Methods: We enrolled 24 patients who underwent stress dynamic CTP using a 256-slice CT. Images were reconstructed using filtered back projection (FBP), hybrid IR, and IMR. Image quality and hemodynamic parameters were compared among three algorithms. Results: Qualitative image quality and contrast-to-noise ratio were significantly higher by IMR than by FBP or hybrid IR (visual score: 4.1 vs. 3.0 and 3.5; contrast-to-noise ratio: 12.4 vs. 6.6 and 8.4; P < 0.05). No significant difference was observed among algorithms in CTP-derived myocardial blood flow (1.68 vs. 1.73 and 1.70 mL/g/min). Conclusions: The use of knowledge-based iterative model reconstruction improves image quality without altering hemodynamic parameters in low-dose dynamic CTP, compared with FBP or hybrid IR.
关键词： iterative reconstruction,myocardial blood volume,myocardial blood flow,computed tomography perfusion,mean transit time
更新于2025-09-12 10:27:22
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Quantitative Analysis of Heel Skin Microcirculation Using Laser Doppler Flowmetry and Tissue Spectrophotometry
摘要： OBJECTIVE: To examine perfusion changes in the heel skin of individuals with and without diabetes mellitus to understand how skin is pathologically affected by diabetes mellitus. METHODS: This case-control study was conducted at an academic hospital in Tuebingen, Germany. A total of 30 subjects were enrolled in the study: 15 with known type 2 diabetes mellitus and 15 without. Each subject was asked to lie in a supine position on a hard lateral transfer mat for 10 minutes. MAIN OUTCOME MEASURES: Heel perfusion was quantitatively assessed directly after relief of pressure and after 3 and 6 minutes after relief of pressure using laser Doppler flowmetry and tissue spectrophotometry. MAIN RESULTS: Directly after relief of pressure, blood flow increased in the superficial skin layers (2 mm below the surface of the skin) in both groups. However, in deep skin layers (8 mm below the surface of the skin), blood flow increased in patients with diabetes mellitus and decreased in healthy patients. Oxygen saturation (SO2) was higher in healthy subjects directly after pressure relief. CONCLUSIONS: The increase in blood flow in superficial skin layers indicates reactive hyperemia after exposure in both groups. The prolonged hyperemia in deep skin layers in patients with diabetes indicates increased tissue vulnerability. Despite the increase in blood flow in deep skin layers, the SO2 and thus supply of tissue in patients with diabetes were reduced.
关键词： diabetes mellitus,pressure injury,oxygen saturation,blood flow,perfusion,diabetic foot ulcers,laser Doppler flowmetry,pressure ulcer,microcirculation
更新于2025-09-12 10:27:22
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Whole-Eye Perfusion Model for Screening of the Ocular Formulations via Confocal Laser Scanning Microscopy
摘要： Various physiological, anatomical barriers make ocular drug delivery very challenging. Hence, better in vitro screening models are needed for rapid screening of the formulations. In this study, a simple whole-eye perfusion model was designed and its application was explored for screening targeted formulation across the full-thickness cornea laser scanning microscopy. PEG-cholecalciferol-based integrin targeted using confocal coumarin-6 micelles (TC6M) and non-targeted coumarin-6 micelles (NTC6M) were developed by solvent diffusion evaporation technique. The formulations NTC6M and TC6M had particles size 23.5 ± 5 nm and 28.5 ± 6 nm respectively and osmolality of 294–300 mOsml/Kg. The whole-eye perfusion model was developed using porcine eye. TC6M and NTC6M were instilled on the excised porcine eyes as well as in the eyes of NZW rabbits. Corneas were excised from the experimental eyes; coumarin-6 penetration across the corneas was analyzed using confocal microscope. Coumarin-6-loaded micelles had particle size below 50 nm. NTC6M formulations showed penetration to the deeper layers up to 500 μm porcine eyes and up to 50 μm in rabbit corneas. However, TC6M formulations exhibited superior retention, as higher ?uorescent intensities were observed in upper layers up to 50 μm depth in the porcine eye and 20 μm depth in rabbit eye. Hence, applicability of whole-eye perfusion model in preliminary screening of the formulations was successfully demonstrated. Whole-eye perfusion model when combined with confocal microscopy has potential to be used as an ef?cient tool for rapid screening and optimization of various ophthalmic formulations.
关键词： coumarin-6,confocal,micelles,perfusion model,ocular
更新于2025-09-11 14:15:04
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Different lasers reveal different skin microcirculatory flowmotion - data from the wavelet transform analysis of human hindlimb perfusion
摘要： Laser Doppler flowmetry (LDF) and reflection photoplethysmography (PPG) are standard technologies to access microcirculatory function in vivo. However, different light frequencies mean different interaction with tissues, such that LDF and PPG flowmotion curves might have distinct meanings, particularly during adaptative (homeostatic) processes. Therefore, we analyzed LDF and PPG perfusion signals obtained in response to opposite challenges. Young healthy volunteers, both sexes, were assigned to Group 1 (n = 29), submitted to a normalized Swedish massage procedure in one lower limb, increasing perfusion, or Group 2 (n = 14), submitted to a hyperoxia challenge test, decreasing perfusion. LDF (Periflux 5000) and PPG (PLUX-Biosignals) green light sensors applied distally on both lower limbs recorded perfusion changes for each experimental protocol. Both techniques detected the perfusion increase with massage, and the perfusion decrease with hyperoxia, in both limbs. Further analysis with the wavelet transform (WT) revealed better depth-related discriminative ability for PPG (more superficial, less blood sampling) compared with LDF in both challenges. Spectral amplitude profiles consistently demonstrated better sensitivity for LDF, especially regarding the lowest frequency components. Strong correlations between components were not found. Therefore, LDF and PPG flowmotion curves are not equivalent, a relevant finding to better study microcirculatory physiology.
关键词： Laser Doppler flowmetry,perfusion,photoplethysmography,wavelet transform,microcirculatory function
更新于2025-09-11 14:15:04