In vivo label-free measurement of blood flow velocity symmetry based on dual line scanning third-harmonic generation microscopy excited at the 1700 nm window

Measurement of bloodflow velocity is key to understanding physiology and pathology in vivo.While most measurements are performed at the middle of the blood vessel,little research has been done on characterizing the instantaneous bloodflow velocity distribution.This is mainly due to the lack of measurement technology with high spatial and temporal resolution.Here,we tackle this problem with our recently developed dual-wavelength line-scan third-harmonic generation(THG)imaging technology.Simultaneous acquisition of dual-wavelength THG line-scanning signals enables measurement of bloodflow velocities at two radially symmetric positions in both venules and arterioles in mouse brain in vivo.Our results clearly show that the instantaneous bloodflow velocity is not symmetric under general conditions.

Changes in mean cerebral blood flow velocity during cognitive task-induced cerebral fatigue in high performance fighter pilots

BACKGROUND： Several studies have demonstrated that sustained cognitive tasks can induce cognitive fatigue and that the mean cerebral blood flow velocity changes in some cerebral regions during cerebral fatigue. OBJECTIVE： To dynamically monitor the changes in mean cerebral blood flow velocity in different brain regions of high performance fighter pilots during mental arithmetic tasks and consecutive performance tasks. DESIGN, TIME AND SETTING： The present neurophysiological trial, based on controlled observation, was performed at the Laboratory of Neurophysiology, Institute of Aviation Medicine, Air Force of China between January 2003 and December 2005. PARTICIPANTS： Forty-five males, high performance fighter pilots, averaging （27.6±2.5） years, were recruited for this study. METHODS： The mean cerebral blood flow velocity in the anterior cerebral artery, middle cerebral artery, and posterior cerebral artery of subjects was dynamically tested using transcranial Doppler during 5- hour mental arithmetic tasks and during 5- hour consecutive performance tasks. The neurobehavioral ability index was analyzed throughout each trial according to the number of correct responses, false responses, and lost responses. Simultaneously, cerebral cognitive fatigue-induced lethargy was assessed by the Stanford Sleepiness Scale. MAIN OUTCOME MEASURES： Changes in mean cerebral blood flow velocity in the anterior cerebral artery, middle cerebral artery, and posterior cerebral artery; neurobehavioral ability index of mental arithmetic and consecutive performance tasks; Stanford Sleepiness Scale scores. RESULTS： During mental arithmetic tasks, the mean cerebral blood flow velocity in the anterior cerebral artery increased during hour 2 and decreased after hour 4. There was no significant change in mean cerebral blood flow velocity in the middle cerebral artery and posterior cerebral artery. During hour 4, cerebral cognitive fatigue was observed and, simultaneously, Stanford Sleepiness Scale scores demonstrated the presence of fatigue. During such a stage, the neurobehavioral ability index decreased, indicating a decline in performance ability. During consecutive performance tasks, the mean cerebral blood flow velocity declined earlier in the posterior cerebral artery compared to the middle cerebral artery. CONCLUSION： Five- hour mental arithmetic tasks have few effects on cerebral functions and do not lead to a significant change in mean cerebral blood flow velocity. Five-hour consecutive performance tasks can induce cerebral cognitive fatigue, and a marked decline in mean cerebral blood flow velocity.

RETINAL SPECTRAL IMAGING AND BLOOD FLOW MEASUREMENT

Measurement of both oxygen saturation and blood flow in the retinal vessels has proved to give important information about the eye health and the onset of eye pathologies such as diabetic retinopathy.In this study,we present the implementation,on a commercially available fundus camera,of a retinal imager and a retina blood flow velocimeter.The retinal imager uses division of aperture to acquire nine wavelength-dependent sub-images of the retina.Careful consideration is taken to improve image transfer by measuring the optical properties of the fundus camera and modeling the optical train in Zemax.This part of the setup is calibrated with optical phantoms of known optical properties that are also used to build a lookup table(LUT)linking phantom optical properties to measured reflectance.The retina blood flow velocimeter relies on tracking clusters of erythrocytes and uses a fast acquisition camera attached to a zoom lens,with a green illumination LED-engine.Calibration is provided using a calibrated quartz capillary tube and human blood at a known flow rate.Optical properties of liquid phantoms are retrieved from measured reflectance using the LUT,and blood flow measurements in the retina are presented.

Close Correlations Between Carotid Arterial Mean Blood Flow Velocity,Body Mass Index,and Temperature in Normal Individuals

Objective:Assessing carotid and radial pulses is an essential sphygmology method in traditional Chinese medicine(TCM).It is believed in TCM and by doctors that pulse force is markedly linked with the physiological state of a human,including body mass index(BMI)and temperature.However,comprehensive analysis elucidating these potential correlations remains undetermined.Therefore,this investigation aimed to assess the association of pulse strength with human metabolism.Materials and Methods:The mean blood flow velocity(MBFV)of the carotid artery and pulse force of 122 healthy adults included in this investigation were assessed using ultrasound and manual palpation.Their thermal texture map was also acquired.Results:No substantial variation was observed in the carotid arterial MBFV among normal individuals(P>0.05)regardless of body side and gender.However,young individuals had higher blood velocity than middle-aged individuals(P<0.05).Furthermore,it was identified that MBFV was negatively associated with BMI and torso temperature;however,it was positively linked with hand temperature.Conclusions:This investigation revealed that carotid arterial MBFV could indicate the physical state of humans,including BMI and temperature,and therefore,is valuable for elucidating the effect of TCM on yin–yang.The data validated some TCM beliefs and supported the implementation of sphygmology in TCM.

Handgrip exercise elevates basilic venous hemodynamic parameters in healthy subjects

Purpose:This study examined the effect of handgrip exercise on hemodynamic indices to determine the most effective regimen for promoting blood circulation.Methods:Healthy individuals were divided into three treatment groups with each performing exercises using an electronic handgrip.Groups performed exercises to determine the most appropriate tap position,frequency,and duration.The hemodynamic indices were measured by Doppler ultrasound.Results:The best handgrip position was the weak tap position.Venous blood flow velocity and blood flow increased significantly with each exercise relative to the resting state(p<0.01).Venous blood flow velocity and blood flow peaked with handgrip exercise frequency of 25 times/min for 2 min(p<0.01).No significant differences were observed between sexes.Conclusion:Handgrip exercise is an effective method for improving blood circulation in the upper extremities.

Compromised cerebrovascular modulation in chronic anxiety:evidence from cerebral blood flow velocity measured by transcranial Doppler sonography

Objective Cerebral autoregulation （CA） is the mechanism by which constant cerebral blood flow is maintained despite changes in cerebral perfusion pressure. CA can be evaluated by dynamic monitoring of cerebral blood flow velocity （CBFV） with transcranial Doppler sonography （TCD）. The present study aimed to explore CA in chronic anxiety. Methods Subjects with Hamilton anxiety scale scores 〉14 were enrolled and the dynamic changes of CBFV in response to an orthostatic challenge were investigated using TCD. Results In both the anxious and the healthy subjects, the mean CBFV was significantly lower in the upright position than when supine. However, the CBFV changes from supine to upright differed between the anxious and the healthy groups. Anxious subjects showed more pronounced decreases in CBFV with abrupt standing. Conclusion Our results indicate that cerebrovascular modulation is compromised in chronic anxiety; anxious subjects have some insufficiency in maintaining cerebral perfusion after postural change. Given the fact that anxiety and impaired CA are associated with cardiovascular disease, early ascertainment of compromised cerebrovascular modulation using TCD might suggest interventional therapies in the anxious population, and improve the primary prevention of cardiovascular disease.

Cynodon dactylon andSida acuta extracts impact on the function of the cardiovascular system in zebrafish embryos

The aim of the present study was to screen cardioactive herbs from Western Ghats of India. The heart beat rate （HBR） and blood flow during systole and diastole were tested in zebrafish embryos. We found that Cynodon dactylon （C. dactylon） induced increases in the HBR in zebrafish embryos with a HBR of （3.968±0.344） beats/ s, which was significantly higher than that caused by betamethosone [（3.770±0.344） beats/s]. The EC50 value of C. dactylon was 3.738 μg/mL. The methanolic extract of Sida acuta （S. acuta） led to decreases in the HBR in zebrafish embryos [（1.877 ±0.079） beats/s], which was greater than that caused by nebivolol （positive control）. The EC50 value of Sida acuta was 1.195 μg/mL. The untreated embryos had a HBR of （2.685±0.160） beats/s at 3 d post fertilization （dpf）. The velocities of blood flow during the cardiac cycle were （2,291.667 ±72.169） μm/s for the control, （4,250± 125.000） μm/s for C. dactylon and （1,083.333±72.169） μm/s for S. acuta. The LC50 values were 32.6 μg/mL for C. dactylon and 20.9 μg/mL for S. acuta. In addition, the extracts exhibited no chemical genetic effects in the drug dosage range tested. In conclusion, we developed an assay that can measure changes in cardiac function in response to herbal small molecules and determine the cardiogenic effects by microvideography.

Recent advancement in diagnosis of vasculogenic impotence

Several dynamic tests with vasoactive drags are available for evaluating penile vascular inflows and outflows,ranging from simple pharmacologic test to more invasive radiologic sets. However, there is still no perfect single testto reflect the penile vascular flow. All possible efforts should be exerted to get the greatest erectile effect to avoid anunderestimation of blood flow to the corpora due to incomplete relaxation of the trabecular smooth muscle.Appreciation of the type and frequency of anatomical variations and potential collateral routes is important in interpretingpenile arterograms and in evaluating the hemodynamic significance of suspected arterial disease. Choice of the vasculartests should always depend on the purpose of testing.

Clinical Significance of Fetal Cerebral and Umbilical Arte-rial Blood Flow Velocity Wave Forms Examination.

Color Doppler was used to examine the blood flow velocity wave forms of fetal middle cerebral artery (MCA) and umbilical artery (UA) in normal pregnancy (58 cases) pregnancy induced hypertension (PIH) with fetal growth retardation (IUGR) (54 cases) and without IUGR (34 cases). The peak-systolic / diastole ratio (S/D), pulse index (PI) and resistance index (RI) values of MCA and UA were calcu-

Effect of Physical Intervention on Preventing Upper Limb Venous Thrombosis of Patients with PICC: A Systematic Review and Meta-Analysis of Randomized Trials

Objective: To evaluate the effect of physical methods on the prevention of venous thrombosis in patients with peripherally inserted central catheter (PICC). Methods: Randomized controlled trials meeting the inclusion and exclusion criteria were retrieved from the following databases: Cochrane library, Pubmed, EMbase, Web of science, Ovid, CBM, CNKI, Wanfang, VIP, then Review Manage (RevMan) 5.3 software was used for data analysis. Results: A total of 24 RCTs including 3496 patients were analyzed in the study. The results of meta-analysis showed that various forms of upper limb movements could effectively decrease the incidence of venous thrombosis in the patients with PICC [RR = 0.23, 95% CI (0.16, 0.33), P < 0.01], upper limb movements could effectively improve the mean blood flow velocity of basilic vein [MD = 1.65, 95% CI (1.19, 2.11), P < 0.01]. Conclusion: Upper limb movements can effectively decrease the incidence of phlebothrombosis and improve the mean flow velocity of basilic vein in the patients undergoing PICC. Other forms of physical prevention methods need to be further studied due to insufficient sample size.

Effect of swimming training on neural microcirculation in rats with sciatic nerve compression A study based on laser Doppler flowmetry

Microcirculation of the peripheral nerve is necessary for neural growth and regeneration. However, technical limitations have limited studies in this area. The few studies conducted have concerned active exercise effects on microcirculation of the peripheral nerve. Using an animal experiment, this study evaluated the effect of swimming training on microcirculation of injured peripheral nerve by laser Doppler flowmetry. The results showed that the blood vessel at the distal end of the peripheral nerve was the main blood supply for the nerve, and the internal blood supply for the nerve had strong compensatory ability. Swimming training promoted the functional recovery of rats with sciatic nerve injury and the regeneration of myelin sheath and blood vessels, but had no impact on neural blood flow.

The inter-visit variability of retinal blood flow velocity measurements using retinal function imager (RFI)

Background:To determine the inter-visit variability of retinal blood flow velocities(BFVs)using a retinal function imager(RFI)in healthy young subjects.Methods:Twenty eyes of 20 healthy young subjects were enrolled.RFI imaging was performed to obtain the BFVs in retinal arterioles and venules in a field measuring 7.3×7.3 mm^(2)(setting:35 degrees)centered on the fovea,and repeated measurements were obtained on two separate days.The inter-visit variability of BFVs was assessed by the concordance correlation coefficient(CCC)and coefficient of variance(CV).Results:At the first visit,the mean BFV was 3.6±0.8 mm/s and 3.0±0.7 mm/s in arterioles and venules,respectively,which were not significantly different from those at the second visit(the BFV of arterioles was 3.5±0.8 mm/s,and the BFV of venules was 3.0±0.7 mm/s,P>0.05,respectively).The CCC was 0.72 in the BFVs of arterioles and 0.67 in venules,and the CV was 10.8%in the BFVs of arterioles and 11.0%in venules.Conclusion:The inter-visit variability using the retinal function imager(RFI)with a large field of view appeared to be good and comparable to previously reported intra-visit and inter-eye variability.

Pre-and postoperative changes of regional cortical cerebral blood flow in patients with cerebral arteriovenous malformation

Objective To investigate pre- and postoperative changes of regional cerebral cortical blood flow in patients with cerebral arteriovenous malformation. Method Twenty-two adult patients with arteriovenous malformation(AVM) were recruited into this study at Beijing Tiantan Hospital from September 2001 to May 2002. Eight patients had giant cerebral AVM and the other 14 had a small one. Cortical cerebral blood flow (CBF) was measured by laser Doppler flowmetry (LDF) before and after AVM resections. After surgery,the probe of LDF was implanted adjacent to the area of AVM and monitored for 24 hours.Results CBF increased significantly after the resection in all patients regardless of AVM size. In patients with small AVM,CBF returned to the baseline level within 4 hours,but in patients with giant AVM,CBF remained high even after 24 hours.Conclusions Monitoring CBF is helpful to understand pre- and postoperative changes of regional cortical CBF in patients with cerebral AVM.

Left atrial appendage flow velocity in rheumatic mitral stenosis

The left atrial appendage ( LAA ) has been considered a relatively insignificant portion of the cardiac anatomy. Because thrombi have been found to have a predilection to form within the LAA, a better understanding of the LAA is necessary. Transesophageal echocardiography (TEE) is a technique that makes clear imaging of the

Microvascular blood flow velocities measured with a retinal function imager: inter-eye correlations in healthy controls and an exploration in multiple sclerosis

Background:The retinal microcirculation has been studied in various diseases including multiple sclerosis(MS).However,inter-eye correlations and potential differences of the retinal blood flow velocity(BFV)remain largely unstudied but may be important in guiding eye selection as well as the design and interpretation of studies assessing or utilizing retinal BFV.The primary aim of this study was to determine inter-eye correlations in BFVs in healthy controls(HCs).Since prior studies raise the possibility of reduced BFV in MS eyes,a secondary aim was to compare retinal BFVs between MS eyes,grouped based on optic neuritis(ON)history and HC eyes.Methods:Macular arteriole and venule BFVs were determined using a retinal function imager(RFI)in both eyes of 20 HCs.One eye from a total of 38 MS patients comprising 13 eyes with ON(MSON)and 25 eyes without ON(MSNON)history were similarly imaged with RFI.Results:OD(right)and OS(left)BFVs were not significantly different in arterioles(OD:3.95±0.59 mm/s;OS:4.08±0.60 mm/s,P=0.10)or venules(OD:3.11±0.46 mm/s;OS:3.23±0.52 mm/s,P=0.06)in HCs.Very strong inter-eye correlations were also found between arteriolar(r=0.84,P<0.001)and venular(r=0.87,P<0.001)BFVs in HCs.Arteriolar(3.48±0.88 mm/s)and venular(2.75±0.53 mm/s)BFVs in MSNON eyes were significantly lower than in HC eyes(P=0.009 and P=0.005,respectively).Similarly,arteriolar(3.59±0.69 mm/s)and venular(2.80±0.45 mm/s)BFVs in MSON eyes were also significantly lower than in HC eyes(P=0.046 and P=0.048,respectively).Arteriolar and venular BFVs in MSON and MSNON eyes did not differ from each other(P=0.42 and P=0.48,respectively).Conclusions:Inter-eye arteriolar and venular BFVs do not differ significantly in HCs and are strongly correlated.Our findings support prior observations that arteriolar and venular BFVs may be reduced in MS eyes.Moreover,this seems to be the case in both MS eyes with and without a history of ON,raising the possibility of global blood flow alterations in MS.Future larger studies are needed to assess differences in BFVs between MSON and MSNON eyes.

Prognostic value of Doppler transmitral filling patterns in patients with chronic heart failure

Background Chronic heart failure is a significant cause of cardiovascular morbidity and mortality. This study tested the hypothesis that restrictive filling pattern may provide useful prognostic data for identifying patients with chronic heart failure at high risk of all-cause cardiac death.Methods Ninety patients with chronic heart failure [ 70 men and 20 women, mean age (58.1 ± 11.6) years] were investigated and followed for (18. 8 ±7. 9) months. During this period, 14 patients died of progressive pump failure, 12 patients underwent heart transplantation, 5 patients died suddenly, and 2 patients died of acute myocardial infarction. A new criterion, the restrictive filling index (RFI), was designed to subgroup patients into a restrictive and a nonrestrictive group.Results Patients with restrictive filling pattern had a more severe left ventricular dysfunction and a higher cardiac mortality. Analysis by the Kaplan-Meier method revealed that patients in the RFI≥1 and RFI <1 groups had a cardiac events-free survival rate of 52% versus 94% at 1 year, and 27. 5% versus 92% at 2 years, respectively. The multivariate Cox proportional hazard model selected RFI as the most powerful prognostic factor (x2 =8. 8017, P=0. 0030) for all-cause cardiac death.Conclusion These results indicate that RFI is a simple, noninvasive, and specific clinical predictor for adult chronic heart failure patients who are at a high risk for all-cause cardiac death.

Retinal nerve fiber layer (RNFL) integrity and its relations to retinal microvasculature and microcirculation in myopic eyes

Background:The aim was to determine retinal nerve fiber layer function and its relations to retinal microvasculature and microcirculation in patients with myopia.Method:Polarization-sensitive optical coherence tomography(PS-OCT)was used to measure phase retardation per unit depth(PR/UD,proportional to the birefringence)of the retinal nerve fiber layer(RNFL).Optical coherence tomography angiography(OCTA)was used to measure macular vessel density analyzed using fractal analysis.In addition,a retinal function imager(RFI)was used to measure macular blood flow velocities in arterioles and venules.Twenty-two patients with moderate myopia(MM,refraction>3 and<6 diopters),seventeen patients with high myopia(HM,≥6 D)and 29 healthy control subjects(HC,≤3.00 D)were recruited.One eye of each patient was imaged.Results:Although the average PR/UD of the RNFL in the HM group did not reach a significant level,the birefringence of the inferior quadrant was significantly lower(P<0.05)in the HM group compared to the HC group.Significant thinning of the average RNFL and focal thinning of RFNL in temporal,superior and inferior quadrants in the HM group were found,compared to the HC group(P<0.05).There were no significant differences of retinal blood flow velocities in arterioles and venules among groups(P>0.05).The macular vessel density in both superficial and deep vascular plexuses was significantly lower in the HM group than in the other two groups(P<0.05)as well as in the MM group than in the HC group(P<0.05).The average PR/UD and PR/UD in the inferior quadrant were not related to refraction,axial length,blood flow velocities and macular vessel densities(r ranged from−0.09 to 0.19,P>0.05).Conclusions:The impairment of the retinal nerve fiber birefringence in the HM group may be one of the independent features in high myopic eyes,which appeared not to relate to macular microvascular density and blood flow velocity.

Inter-visit measurement variability of conjunctival vasculature and circulation in habitual contact lens wearers and non-lens wearers

Background:The inter-visit variation of measuring bulbar conjunctival microvasculature and microcirculation needs to be considered when the results from multiple visits are interpreted.This study examined the inter-visit variability of measuring conjunctival microvasculature and microcirculation in habitual contact lens(HCL)wearers and non-contact lens(NCL)wearers.Methods:Twenty-eight subjects were recruited including 13 HCL wearers(10 females and 3 males;mean age±standard deviation,25.8±4.6 years)who had worn contact lenses on a daily basis for at least 3 years and 15 NCL wearers(10 females and 5 males,age 25.5±4.0 years)were recruited.The temporal bulbar conjunctiva was imaged using a functional slit-lamp bio-microscope(FSLB)imaging system.FSLB imaging was performed in the morning when the HCL wearers did not wear their lenses.The measurements included conjunctival vessel diameter,vessel density,blood flow velocity and flow volume.In addition,conjunctival microvasculature was analyzed using monofractal(Dbox,representing vessel density)and multifractal(D0 representing vessel complexity)analyses.The repeated measurement was conducted at least one week after the first visit and both eyes of each participant were imaged.The coefficient of variation(CV)was calculated as the standard deviation of the differences between test and re-test then divided by the mean of the measurements.The intra-class correlation coefficient(ICC)was also calculated.Results:No significant differences of all vascular measurements in both the right and left eyes were found between two groups(P>0.05).Between two measurements on two different visits,the CV was from 2.4%(vessel density D0)to 63.5%(blood flow volume Q)in HCL wearers and from 3.4%(D0)to 40.6%(blood flow volume)in NCL wearers.The ICC was from 0.60(vessel diameter)to 0.81(axial blood flow velocity VA)in HCL wearers and from 0.44(Q)to 0.68(cross-sectional blood flow velocity VS)in NCL wearers.Conclusions:The measurement variability of the vessel density of the bulbar conjunctiva appeared to have the smallest inter-visit variation.The measurement variability of the vasculature and circulation in HCL wearers were similar to that in NCL wearers.

Microcirculation in the conjunctiva and retina in healthy subjects

Background:The aim was to determine the relationship between bulbar conjunctival microcirculation and retinal microcirculation in a healthy population.Method:A functional slit-lamp biomicroscope(FSLB)was used to measure blood flow velocity(BFV)and blood flow rate(BFR)in the conjunctiva while a retinal function imager(RFI)was used to measure macular BFV and BFR in the retina.One eye of each subject of 58 self-reported healthy subjects was imaged in the same session on the same day.Results:The mean BFV in the venules of the conjunctiva was 0.49±0.13 mm/s,which was significantly slower than that in the retinal arterioles(3.71±0.78 mm/s,P<0.001)and retinal venules(2.98±0.58 mm/s,P<0.001).The BFR in the conjunctiva(0.09 nl/s)was also significantly lower than that in the retina(arterioles=0.81 nl/s,venules=0.68 nl/s,all P<0.001).The BFVs and BFRs were not related between the conjunctiva and retina(r ranged from−0.17 to−0.05,all P>0.05).Conclusion:The microcirculation in the retina appeared to be different from that in the conjunctiva.

The retinal function imager and clinical applications

Background:The Retinal Function Imager(RFI)provides in vivo and noninvasive imaging of both the retinal structure and function.Review:The RFI can create capillary perfusion maps,measure blood flow velocity,and determine metabolic function including blood oximetry.It can aid clinical diagnosis as well as assess treatment response in several retinal vascular diseases including diabetic retinopathy.Blood flow velocity abnormalities have also been implicated in disease such as age-related macular degeneration and require further investigation.Compared with optical coherence tomography angiography,the RFI produces capillary maps of comparable image quality and wider field of view but it is unable to provide depth-resolved information and has longer image acquisition time.Currently,functional imaging using blood oximetry has limited applications and additional research is required.Conclusion:The RFI offers noninvasive,high-resolution imaging of retinal microvasculature by creating capillary perfusion maps.In addition,it is capable of measuring retinal blood velocity directly and performs functional imaging with retinal blood oximetry.Its clinical applications are broad and additional research with functional imaging may potentially lead to diagnosis of diseases and their progression before anatomic abnormalities become evident,but longer image acquisition times may limit its clinical adoption.