Laser Doppler Flowmetry Measurements Research Articles

Microcirculatory Dysfunction in Patients With Diabetes Mellitus Detected by a Distributed System of Wearable Laser Doppler Flowmetry Analysers.

The paper is devoted to the study of perfusion and amplitude-frequency spectra of laser Doppler flowmetry (LDF) signals in patients with diabetes mellitus (DM) in different skin areas of the upper and lower extremities using a distributed system of wearable LDF analysers. LDF measurements were performed in the areas of the fingers, toes, wrists and shins. The mean perfusion values, the amplitudes of blood flow oscillations in endothelial, neurogenic, myogenic, respiratory and cardiac frequency ranges, and the values of nutritive blood flow were analysed. The results revealed a decrease in tissue perfusion and nutritive blood flow in the lower extremities and an increase in these parameters in the upper extremities in patients with DM. A decrease in the amplitudes of endothelial and neurogenic oscillations was observed. The obtained results confirm the possibility of using wearable LDF analysers to detect differences in the blood flow regulation in normal and pathological conditions.

Reproducibility of Laser Doppler Flowmetry in gingival microcirculation. A study on six different protocols

ObjectivesLaser Doppler Flowmetry (LDF) is a non-invasive technique for the assessment of tissue blood flow, but increased reproducibility would facilitate longitudinal studies. The aim of the study was to assess the interday reproducibility of Laser Doppler Flowmetry (LDF) at rest, at elevated local temperatures, and with the use of the vasodilator Methyl Nicotinate (MN) in six interconnected protocols for the measurement of the blood supply to the microvascular bed of the gingiva. MethodsTen healthy volunteers were included. Interweek LDF measurements with custom-made acrylic splints were performed. Six protocols were applied in separate regions of interest (ROI): 1; basal LDF, 2; LDF with thermoprobe 42 °C, 3; LDF with thermoprobe 45 °C, 4; LDF with thermoprobe 42 °C and MN, 5; LDF with thermoprobe 45 °C and MN and 6; LDF with MN. ResultsIntra-individual reproducibility was assessed by the within-subject coefficient of variation (wCV) and the intraclass correlation coefficient (ICC). Basal LDF measurements demonstrated high reproducibility with wCV 11.1 in 2 min and 10.3 in 5 min. ICC was 0.9 and 0.92. wCV after heat and MN was 4.9–10.3 and ICC 0.82–0.93. The topically applied MN yielded increased blood flow. ConclusionThis is the first study evaluating the reproducibility of basal LDF compared to single or multiple vasodilatory stimuli in gingiva. Multiple collector fibers probe and stabilizing acrylic splints are recommended. Vasodilatory stimulation showed a tendency toward higher reproducibility. Furthermore, MN yields vasodilation in gingiva.

Poster 225: Acetabular Labral Blood Flow Using Laser Doppler Flowmetry Before & After All- Arthroscopic Capsular Autograft Labral Reconstruction

Objectives: All-arthroscopic capsular autograft labral reconstruction has been proposed to repair complex or irreparable tears without the downside of autograft related donor-site morbidity. Cadaveric studies have suggested that the acetabular labrum receives its blood supply from radial branches of the periacetabular periosteal vascular ring that penetrate the hip capsule, with perfusion remaining intact in most hips exhibiting labral tears. Despite this, little is known about the exact course of blood flow to labral tissue or how surgical reconstruction of this region affects microvasculature during hip arthroscopy. The purpose of this study was to examine the effects of all-arthroscopic capsular autograft labral reconstruction on labral blood flow in vivo using laser doppler flowmetry (LDF) to measure microvascular perfusion. Methods: After obtaining institutional review board approval, patients ≥18 years old undergoing arthroscopic repair of the acetabular labrum by a single surgeon were consented between 2018-2022. Labral repair was performed via a previously published capsular autograft labral reconstruction technique. An LDF probe (Moor Instruments) continuously measured microvascular blood flow flux (perfusion units [PU]) within 1mm3 of surrounding labral tissue (Figure 1). LDF measurements were taken medial and lateral to the region of the tear before/after labral reconstruction and before/after labral elevation from the acetabular rim. The mean of flux measurements was expressed as a percent change from each patient’s baseline measurements. The percent change in labral perfusion was analyzed using student t-tests and one-way ANOVA using Tukey’s method for multiple comparisons. Associations between preoperative demographics and labral perfusion were analyzed using multiple regression analyses. Lending from previous literature, flux decreases ≥50% were considered clinically significant. Results: This study included 41 patients [24 males (58.5%) and 17 females (41.5%)] undergoing arthroscopic labral repair with capsular autograft reconstruction with mean [SD] age 31.3 [8.4] years, BMI 24.8 [3.3] kg/m2, lateral center edge angle (LCEA) 35.3 [4.9] degrees, Tönnis angle 5.8 [5.8] degrees, and mean arterial pressure 96.0 [10.9] mmHg. The mean [95% CI] percent change in blood flow following labral elevation was -9.24% [(-0.04) to (-18.1)]. Following labral reconstruction, the mean [95% CI] percent change in blood flow medially was -22.3% [(-11.9) to (-32.7)] and laterally -32.5% [(-23.6) to (-41.5)]. There was no significant difference between the changes in medial versus lateral perfusion (p=0.136) following repair. Unadjusted analyses stratifying for age, BMI, sex, type of impingement, Tönnis/Outerbridge class, amount of capsule used for augmentation, and suture technique revealed that none of these factors were correlated with significant differences in labral perfusion medially or laterally (p>0.05; Table 1). Multiple regression analyses controlling for demographic and intra-operative variables demonstrated that BMI, LCEA, suture technique, age, mean arterial pressure were not significantly associated with changes in medial or lateral labral perfusion (p>0.05; Table 2). Finally, all changes in flux were found to be significantly less than the 50% threshold, when comparing decreases following labral elevation (p<0.001) and labral reconstruction medially (p<0.001) and laterally (p<0.001). Conclusions: While the vascular nature of the acetabular labrum has been described in literature, preservation of labral blood flow following arthroscopic labral repair has not yet been objectively reported. This study found that techniques to preserve native hip anatomy and vascular supply may adequately maintain perfusion to labral tissue and promote healing. While laser doppler flowmetry may be affected by secondary operative factors, careful measures were taken to standardize the in vivo environment during each measurement. Additionally, blood flow measurements are only limited time assessments with no ability to speculate if observed changes are permanent or temporary. Although this study cannot be generalized to all variations of labral repair/reconstruction, these results suggest that surgeons can employ techniques that preserve microvascular tissue perfusion. The use of capsular augmentation enables preservation of the donor-tissue blood supply with local tissue transfer, suggesting that current labral repair techniques can preserve labral perfusion. [Table: see text] [Table: see text]

Comparative Analysis of Methods of Laser Doppler Flowmetry and Doppler Ultrasound Measurement of Blood Flow during the Procedure of Intermittent Pneumatic Compression

The results of the analysis of microcirculation of the blood flow of the toe and ultrasound Doppler measurement of blood flow in the femoral artery during the intermittent pneumatic compression procedure are presented. A professional device “Doctor Life Mark 400” (South Korea) was used for the pressotherapy procedure. Microcirculation was measured using a portable laser Doppler flowmeter “LAZMA PF” (Russia). Ultrasonic Dopplerograms were obtained using the device “Edan U50” (China) with a linear sensor model L15-7b with a frequency in pulsed Doppler mode (PW) 7.2 MHz. The study involved a group of 11 subjects without identified vascular disorders, the age of the group was from 23 to 42 years. The method of calculating the average speed and volume of blood flow over the period of the cardiac cycle was used for ultrasound Dopplerograms. Arterial resistance was evaluated, which was compared with the dynamics of perfusion in the limb. In the studies, approximately half of the test subjects had an increase in perfusion of the microcirculatory bed and a decrease in resistance of arterial vessels. At the same time, with an increase in the perfusion of the microcirculatory bed, a decrease in the resistance of arterial vessels was observed.

Reproducibility and Effect of Sampling Depth on Laser Doppler Flowmetry Measures During the Reflex Cutaneous Vasoconstriction Response

During cold exposure, reflex cutaneous vasoconstriction is an important thermoregulatory mechanism that minimizes heat loss. Laser Doppler flowmetry (LDF) is a widely used, non-invasive method of assessing cutaneous microvascular blood flow. However, data on the reproducibility of LDF during a cooling stimulus is limited. Furthermore, various sampling depths of skin measurement are available depending on the type of LDF probe used; however, a comparison of different depths to the same cooling stimulus has not been determined. We hypothesized that LDF probes, particularly those sampling at deeper skin depths, would provide a reproducible measurement of cutaneous microvascular blood flow during whole-body cooling. Fourteen healthy, young adults completed two whole-body cooling bouts, each bout separated by 3-7 days. Participants wore a water-perfused whole-body suit to reduce skin temperature (Tsk) from 34°C to 30.5°C over 30 minutes, and held at 30.5°C for an additional 10 minutes. LDF flux was measured continuously at five forearm sites using 1 VP1-HP Doppler probe, 2 VP7b integrated probes, and 2 VP12 single point Dopplers (Moor Instruments, Axminster, UK) measuring at depths of 4.0 mm, 0.66 mm, and 0.33 mm, respectively. Cutaneous vascular conductance (CVC) was calculated as flux/mean arterial pressure at each 0.5°C reduction in Tsk and at plateau. CVC values were expressed as percent changes from baseline (%ᐃCVCBASELINE). A greater vasoconstriction response was recorded using the VP1-HP Doppler at plateau (34.7 ± 0.6%) compared to the VP7b (31.9 ± 0.5%, p < 0.001) and VP12 (30.3 ± 0.6%, p < 0.001) LDF probes. Additionally, test-retest reproducibility between visits displayed good reproducibility (coefficient of variation <9%) among all three Doppler probes. These data indicate that LDF provides reproducible measurements during reflex cutaneous vasoconstriction at different depths. However, deeper Dopplers, which analyze a greater area of skin, are more likely to discriminate differences in cutaneous microvascular blood flow than those at shallower depths.

The Decisive Role of Laser Doppler Flowmetry for Pulp Preservation in Discolored Traumatized Teeth.

Objective: It has been stated that blood pigments within discolored teeth may interfere with Laser Doppler Flowmetry (LDF) measurements. The aim of this study was to assess pulp vitality with LDF in a cohort of discolored traumatized teeth referred for endodontic treatment or where the referring dentist had doubts regarding maintained tooth vitality. Background: Discoloration of teeth is a common sequel of dental trauma. Still today, it is taken as an indicator for root canal treatment. Transient apical breakdown (TAB) is confused with apical periodontitis, although it is a sequel of dental trauma in young mature teeth and will result in revascularization and dissolution of the apical radiolucency. Methods: A total of 26 patients with 28 discolored teeth, belonging to a cohort of referred patients with traumatized teeth referred for root canal treatment and/or pulp vitality assessment were screened on color with photographs by three investigators, with traditional sensibility tests and with a Moor VMS II LDF meter. Results: The color of the intrinsically discolored teeth was grayish in 58% of teeth, blue 20%, pink/crimson 12%, and yellow 4%. Eighty-five percent were central maxillary incisors, 11% were mandibulary incisors. Thanks to LDF, 43% of the trauma cases in this small cohort with discoloration underwent root canal treatment instead of 70% with traditional sensibility tests as indicator. TAB was found in 11%. Conclusions: LDF was decisive in diagnosing vitality of discolored teeth and there was no negative impact of tooth discoloration on LDF measurements.

Evidence Based Burn Depth Assessment Using Laser-Based Technologies: Where Do We Stand?

Early clinical assessment of burn depth and associated healing potential (HP) remains extremely challenging, even for experienced surgeons. Inaccurate diagnosis often leads to prolonged healing times and unnecessary surgical procedures, resulting in incremental costs, and unfavorable outcomes. Laser Doppler imaging (LDI) is currently the most objective and accurate diagnostic tool to measure blood flow and its associated HP, the main predictor for a patient's long-term functional and aesthetic outcome. A systematic review was performed on non-invasive, laser-based methods for burn depth assessment using skin microcirculation measurements to determine time to healing: Laser Doppler flowmetry (LDF), LDI and laser speckle contrast imaging (LSCI). Important drawbacks of single point LDF measurements are direct contact with numerous small points on the wound bed and the need to carry out serial measurements over several days. LDI is a fast, "non-contact," single measurement tool allowing to scan large burned areas with a 96% accuracy. LDI reduces the number of surgeries, improves the functional and aesthetic outcome and is cost-effective. There is only limited evidence for the use of LSCI in burn depth assessment. LSCI still needs technical improvements and scientific validation, before it can be approved for reliable burn assessment. LDI has proven to be invaluable in determining the optimal treatment of a burn patient. For unclear reasons, LDI is still not routinely used in burn centers worldwide. Additional research is required to identify potential "barriers" for universal implementation of this evidence-based burn depth assessment tool.

Analysis of pigmented skin lesions and malignant melanoma by Laser Doppler flowmetry - Report of different cases and further analysis by a neuronal network.

Dermatoscopy is successfully used for the early diagnosis of suspicious skin lesions, however, correct diagnosis depends on training. There is evidence that wavelet analysis by Laser Doppler flowmetry (LDF) can identify malignant melanomas by their hypervascularization and changes in the capillary morphology. To show the capability of LDF in the distinction of melanomas and benign pigmented skin lesions based on data collected over 16 years. Evaluation of pigmented skin lesions was based on clinical information. The LDF measurements were taken. The suspect lesion was excised afterwards for histological work-up. Four case reports are presented. Data collected over 16 years was processed into a neuronal network to estimate the dignity of the lesion. A total of 517 suspicious lesions were analyzed by LDF. In the histological work-up, 114 lesions turned out to be melanomas, whereas 403 benign naevi were secured. Specificity to detect melanomas was good based on the clinical information. The LDF increases the sensitivity of melanoma detection, which is also illustrated in four case reports. In addition to clinical parameters, such as color and border, information from the LDF can help in the diagnosis of malignant melanomas. The LDF provides information on the vascularization of the skin lesion.

Evaluation of gingival microcirculation in localized periodontitis of traumatic etiology

Relevance. The indispensable study of blood microcirculation of periodontal tissues in patients with localized periodontitis of traumatic etiology (LPTE) alongside with the assessment of the somatic status lets determine the degree of adaptive capacity of the organism. Laser Doppler flowmetry (LDF) allows noninvasively identify preclinical changes in the periodontal blood microcirculation and observe periodontal status at any treatment phase aiming at the confirmation of effectiveness of undertaken measures.Purpose. The objective of this work is to evaluate periodontal blood microcirculation in LPTE for existing latent vascular flow changes and adaptation features.Materials and methods. LDF measurements of periodontal blood microcirculation in 169 patients with mild and medium LPTE, conducted relaxed and with the use of functional cold test, were done.Results. A decrease in the number of functioning capillaries in periodontal tissues (expressed in a decrease of the integral index of microcirculation), a decrease in blood flow variability (σ-standard deviation) and the stress of the functioning of the regulatory blood microcirculation (Cv) were found. Due to outcomes, it was registered that in mild and medium severity LPTE, normal reaction of adaptation detected at 69.6% and 43.4% cases, respectively, in the remaining cases reaction of intense adaptation and unsatisfactory response adaptation (only if the moderate degree of LPTE) were fixed.Conclusion. Latent periodontal vascular flow changes and also adaptation characteristics are closely related with the somatic state of the body, in particular with the presence of cardiovascular disease in a group of patients.

Enhanced Antioxidative Defense by Vitamins C and E Consumption Prevents 7-Day High-Salt Diet-Induced Microvascular Endothelial Function Impairment in Young Healthy Individuals.

This study aimed to examine whether the oral supplementation of vitamins C and E during a seven-day high salt diet (HS; ~14 g salt/day) prevents microvascular endothelial function impairment and changes oxidative status caused by HS diet in 51 (26 women and 25 men) young healthy individuals. Laser Doppler flowmetry measurements demonstrated that skin post-occlusive reactive hyperemia (PORH), and acetylcholine-induced dilation (AChID) were significantly impaired in the HS group, but not in HS+C+E group, while sodium nitroprusside-induced dilation remained unaffected by treatments. Serum oxidative stress markers: Thiobarbituric acid reactive substances (TBARS), 8-iso prostaglandin-F2α, and leukocytes’ intracellular hydrogen peroxide (H2O2) production were significantly increased, while ferric-reducing ability of plasma (FRAP) and catalase concentrations were decreased in the HS group. All these parameters remained unaffected by vitamins supplementation. Matrix metalloproteinase 9, antioxidant enzymes Cu/Zn SOD and glutathione peroxidase 1, and leukocytes’ intracellular superoxide production remained unchanged after the protocols in both HS and HS+C+E groups. Importantly, multiple regression analysis revealed that FRAP was the most powerful predictor of AChID, while PORH was strongly predicted by both FRAP and renin-angiotensin system activity. Hereby, we demonstrated that oxidative dis-balance has the pivotal role in HS diet-induced impairment of endothelial and microvascular function in healthy individuals which could be prevented by antioxidative vitamins consumption.

Evaluation of the Effect of Hyaluronic Acid Application on the Vascularization of Free Gingival Graft for Both Donor and Recipient Sites with Laser Doppler Flowmetry: A Randomized, Examiner-Blinded, Controlled Clinical Trial.

This study aimed to evaluate with laser Doppler flowmetry (LDF) the effect of topical hyaluronic acid (HA) application on the vascularization of free gingival graft (FGG) donor and recipient sites during the early wound healing period and to investigate the effect of HA application on the dimensional change of the FGG. Forty systemically healthy, nonsmoking patients who required FGG due to insufficient amount of attached gingiva in a partial edentulism were randomly assigned to a study group: test (FGG+HA) or control (FGG alone). The LDF values of the donor and recipient sites were measured in both groups before the operation and at 4, 7, 10, 14, and 30 postoperative days. LDF measurement of the graft was performed as soon as the graft was taken from the palatal site. FGG dimensions (width, height, and thickness) were assessed and recorded at baseline and on day 30, as well as the percentage of the changes in these values. LDF values of the recipient site in the FGG+HA group were found to be statistically higher than those in the control group on days 4 and 7 (P = .013 and P = .020, respectively); however, no differences were found for days 10, 14, and 30. Additionally, no differences were found for the LDF values of the palatal site between the FGG+HA and control groups (P > .05) at all examined time points. The height of the graft measured on day 30 was statistically higher in the FGG+HA than the control group (P < .001). The percentage change in thickness and height of the FGG was statistically lower in the FGG+HA than control group (P = .028 and P < .001, respectively). Application of HA on the recipient bed under the FGG at the first week of healing allows the formation of a well-vascularized layer, which acts as a barrier against tissue tensions by functioning as a scaffold between the recipient bed and FGG, thus reducing the shrinkage of the graft, especially in the vertical direction. This study further showed that the graft taken from the donor site had a remaining blood perfusion value of its own.

A Preliminary Study on the Feasibility of Detecting Global Acute Cerebral Ischemia by the MIPS Method

Acute cerebral ischemia is an important clinical disease that is usually detected by magnetic resonance imaging or computed tomography. The magnetic inductive phase shift (MIPS) is a new method for detecting cerebral diseases, which is non-invasive, miniaturized, and low-cost. A total of 25 rabbits were studied using a two-coil sensor with a 0.3-200 MHz frequency range, and all the subjects were measured for 1 hour. Based on the rabbit acute cerebral ischemia model, the rabbits were divided into unilateral ligation, bilateral ligation, and non-ligation groups. The results showed that the average MIPS values of the non-ligation, unilateral ligation, and bilateral ligation group were -0.195 ± 0.079°, -4.873 ± 1.042°, and -9.165 ± 2.862° respectively. MIPS distinguished different severities of cerebral ischemia in rabbits with statistical significance (p <; 0.05). Laser Doppler flowmetry (LDF) was used as the gold standard for collecting cerebral blood flow data. The strong correlation between the LDF measurements and the phase shift suggested that the phase shift reflects blood flow changes in the brain. Overall, these results suggest that the MIPS detection method has the potential to provide early detection of global cerebral ischemia. Furthermore, this method effectively distinguished different severities of cerebral ischemia.

Minimally invasive laser Doppler flowmetry is suitable for serial bone perfusion measurements in mice

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.

How standard deviation contributes to the validity of a LDF signal: a cohort study of 8years of dental trauma.

The aim of this cohort study was to document the potential of laser Doppler flowmetry (LDF) for diagnosing tooth vitality in traumatized teeth in a population of 88 referred patients with dental trauma over a period of 8years (2011-2018). The main reason to refer was tooth discoloration (26%), and the main trauma cause was a traffic injury (35%). Taking into account that referral for LDF is best given within the week after trauma, 66% of referrals were overdue. In 73% of cases, root canal treatment could be avoided, and in 65%, the presence of a fixed orthodontic retainer showed beneficial for pulp recovery. Data of 394 teeth were collected and submitted to multilevel modelling statistics. As a general conclusion, both LDF perfusion and concentration values proved to be highly reliable in the appreciation of tooth vitality. The difference of variability of standard deviation and range of LDF measurements involving intra-subject control teeth showed statistically significant in discriminating between vital and non-vital pulps. In non-vital teeth, the diagnostic combination of LDF, sensibility tests and peri-apical X-ray is advised.

The reliability of cutaneous low-frequency oscillations in young healthy males.

Spectral analyses of laser-Doppler flowmetry measures enable a simple and non-invasive method to investigate mechanisms regulating skin blood flow. We assessed within-day and day-to-day variability of cutaneous spectral analyses. Eleven young, healthy males were tested twice in three identical sessions, with 19 to 24days between visits, for a total of six tests. Wavelet data were analyzed at rest, in response to local skin heating to 42 and 44°C, and during 5-minutes PORH. We did this for six frequency bands commonly associated with physiological functions. To assess reliability, we calculated CV and ICC scores. At rest, mean CV for the wavelet data ranged from 21% to 24% and ICC scores ranged from 0.67 to 0.91. During local heating, mean CV scores ranged from 17% to 22% and mean ICC scores ranged from 0.71 to 0.95. For peak PORH, CV ranged from 14% to 23% and the ICC range was 0.88 to 0.97. For the area under the curve of the PORH, CV range was 12% to 21% and ICC range was 0.81 to 0.92. These analyses indicate good-to-excellent reliability of the wavelet data in healthy young males.

Choroidal blood flow after the first intravitreal ranibizumab injection in neovascular age-related macular degeneration patients.

To analyse choroidal blood flow (ChBF) changes after the first intravitreal ranibizumab injection in naïve, age-related macular degeneration (ARMD) patients. Subfoveal ChBF was assessed by laser Doppler flowmetry (LDF) in newly diagnosed ARMD patients. Both treated and untreated eyes were assessed in each subject at each visit before the first intravitreal ranibizumab injection as well as 24hr (day 1) and 7days after (day 7). Central macular thickness (CMT), best-corrected visual acuity (BVCA), systemic haemodynamic parameters and LDF parameters were evaluated at each visit. Nonparametric tests were used to compare data between visits and between treated and untreated eyes. Seventeen ARMD patients were included (12 women and five men, 78±8years old). At day 7 postintravitreal ranibizumab injection, the normalized choroidal blood velocity (ChBVel) change in the treated eye group was significant (-10.2%; p=0.006). The choroidal blood volume (ChBVol) did not change significantly after intravitreal injection of ranibizumab. There was a trend for a reduction in ChBF at day 7 (-9.1%, p=0.08). The sensitivity of the experiment was 12% for ChBVel, 16% for ChBVol and 9% for ChBF. In conclusion, the laser Doppler technique provides feasible and noninvasive measurements of blood flow parameters before and after intravitreal injection of antivascular endothelial growth factor (anti-VEGF) in patients with exudative ARMD. Choroidal blood velocity decreased as early as 7days after intravitreal ranibizumab injection, suggesting a vasoconstriction effect of anti-VEGF in large choroidal vessels in front of choriocapillaris (the site of LDF measurement).

The influence of exercise on ulcer healing in patients with chronic venous insufficiency.

Venous leg ulcer (VLU) affects millions of people, and yet there have been no major advances in its treatment for many decades. Is it the time to change our approach, and try a multidisciplinary one that could bring about a change? The aim of this study is to evaluate whether a regular, home-based exercise could be influential in healing the VLU. Eighty subjects (mean age: 65.13 years) were recruited for 12 weeks. The participants were randomized into a control group (N.=20), a compression therapy group (N.=20), an exercise group (N.=20) and a compression and exercise group (N.=20). The exercise comprised of 10 dorsiflexions each hour while the patient was awake. The first 2 groups did not perform any exercise while the other two did. Baseline and 3-month measurements were performed. These measurements include skin perfusion assessment and ulcer size. All patients showed low tcPO2 in the beginning of the study. At the point of 3 months of exercise, Laser Doppler flowmetry and ulcer size measurements showed significant decrease, P<0.001 in exercise groups, however, no real change was demonstrated in the non-exercise groups. Subjects who were performing exercise showed significant increase in tcPO2 readings after 3 months (P<0.001), whereas the tcPO2 readings remained the same in the non-exercise groups. We concluded that exercise had a significant effect on the VLU healing and this effect may be enhanced further with the help of the compression therapy. The tcPO2 and RF measurements may be seen as useful tools in evaluating the microvascular changes, and monitoring healing and follow up of the venous leg ulcer.

Optical Measurements during Deep Brain Stimulation Lead Implantation: Safety Aspects

Background: Intracerebral hemorrhage (ICH) is the most feared complication in deep brain stimulation (DBS) surgery. The aim of the study was to evaluate patient safety and outcome using laser Doppler flowmetry (LDF) as guidance tool during DBS implantations. Methods: An LDF probe adapted for the stereotactic system was used as guide for creation of the trajectory. The microcirculation along 83 preplanned trajectories was measured with the guide during DBS surgery for movement disorders. The microvascular blood flow levels were investigated for all measurement positions. Medical record and postoperative radiology were retrospectively reviewed. Results: Of 2,963 measurement positions, 234 (7.9%) showed at least a doubled blood flow compared to the surrounding tissue. Of these 2.2% had a more than 5 times higher blood flow in front of the probe tip. Along 1 trajectory, a small ICH was detected during surgery. Increased blood flow was more common close to sulci and verticals. Conclusion: Real-time LDF measurement of the microcirculation using a forward-looking probe during DBS surgery can detect blood flow peaks and further minimize the risk of developing ICH. No separate guide tube is necessary as the probe also creates the trajectory for the DBS lead.

The role of laser Doppler flowmetry tests, serum angiopoietin-2, asymmetric and symmetric dimethylarginine to predict outcome in chronic kidney disease.

The role of biochemical and functional markers of microvascular dysfunction to predict cardiovascular outcomes in nondialyzed chronic kidney disease (CKD) remains unclear. In this prospective cohort study, we assessed whether biochemical [serum level of angiopoietin-2 (Ang-2), asymmetric and symmetric dimethylarginin] and functional (laser Doppler flowmetry) measures of microvascular function predicted cardiovascular events, cardiovascular and all-cause mortality in CKD patients. Postocclusive reactive hyperemia area (PORHHA), acetylcholine and sodium nitroprusside-mediated flow changes were estimated by laser Doppler flowmetry, and Ang-2, asymmetric and symmetric dimethylarginin were assessed in 105 CKD patients at baseline. Multiple failure time Cox-regression analyses with backward elimination were performed to determine the predictors of the combined endpoint of cardiovascular mortality and cardiovascular events or all-cause mortality and cardiovascular events during a median of 66.6 (interquartile range 39.8-80.4) months of follow-up. In univariate models lnAng-2 and lnPORHHA both predicted the cardiovascular outcome besides age, diabetes, baseline cardiovascular disease, brachial pulse pressure and log C-reactive protein. In multivariate analysis lnPORHHA [hazard ratio: 0.66 (95% confidence interval: 0.49-0.89) per ln(mU s)], age [1.03 (1.01-1.06) per year], log C-reactive protein [1.31 (1.06-1.64) per ln(mg/l)] and diabetes [3.33 (1.70-6.53)] remained significant predictors of the cardiovascular outcome, whereas lnAng-2 did not enter the model. Neither of the microvascular variables were an independent predictor of all-cause mortality and cardiovascular events. Among the functional and biochemical microvascular parameters PORHHA seems to improve cardiovascular risk assessment in CKD. Nevertheless the robustness of traditional risk factors seems to outweigh the role of microvascular biomarkers on all-cause mortality and cardiovascular events at this time.

Combining laser-Doppler flowmetry measurements with spectral analysis to study different microcirculatory effects in human prediabetic and diabetic subjects.

We aimed to identify the microcirculatory regulatory mechanisms in diabetic and prediabetic humans using a noninvasive method combining spectral analysis with laser-Doppler flowmetry (LDF) measurements on the skin surface. LDF signals were measured by a moorVMS-LDF device to measure the microcirculatory blood flow flux with a time constant of 0.001s, a cutoff frequency of 14.9kHz, and a sampling frequency of 40Hz. The laser operating wavelength and output power were 400-700nm and 6mW, respectively. LDF signals were obtained noninvasively in 115 subjects, who were assigned to three groups (diabetic, prediabetic, and normal) according to the results of the oral glucose tolerance tests. A Morlet mother wavelet transform was applied to the measured 20-min LDF signals, and periodic oscillations with five characteristic frequency peaks were obtained within the following frequency bands: 0.0095-0.02, 0.02-0.06, 0.06-0.15, 0.15-0.4, and 0.4-1.6Hz (defined as FR1-FR5), respectively. The relative energy contribution (REC) of FR1 was significantly smaller (by using the Kruskal-Wallis test followed by Dunn's multiple-comparison tests) in diabetic subjects than in normal subjects. The REC of FR2-FR3 was significantly smaller in diabetic and prediabetic subjects than in normal subjects. The REC of FR1-FR3 from normal to prediabetic and diabetic subjects showed a progressive decrease. The present findings may aid in the development of a noninvasive method for the early detection of prediabetes and the monitoring of disease progression. This may be useful in preventing disease progression and reducing the risk of concomitant end-organ damage.