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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Characterization of retinal microvasculature in acute non-arteritic anterior ischemic optic neuropathy using the retinal functional imager: a prospective case series

Background:Non-arteritic anterior ischemic optic neuropathy(NAION)is the most common cause of acute optic neuropathy in patients over 50 years of age,and many affected individuals are left with permanent visual deficits.Despite the frequency of NAION and its often devastating effects on vision,no effective treatment has been established.Further understanding of the acute vascular effects in NAION,using advanced ophthalmic imaging techniques like the retinal function imager,may shed light on potential treatment targets.Methods:Five patients with acute NAION underwent retinal functional imaging within 2 weeks of the onset of their visual symptoms,and at 1 month and 3 months after onset.Average arteriolar and venular blood flow velocities were calculated for each eye at each time point.The Wilcoxon rank sum test was used to compare blood flow velocity results with a normative database.Results:The average arteriolar blood flow velocity in the normative group was 3.8 mm/s,and the average venular blood flow velocity was 3.0 mm/s,versus 4.1 mm/s and 2.7 mm/s,respectively,in the NAION-affected group at presentation.Average arteriolar blood flow increased slightly to 4.2 mm/s one month after the acute NAION event,then decreased to 3.8 mm/s three months after the event.Average venular blood flow velocity was 2.8 mm/s 1 month after the NAION event and 2.7 mm/s 3 months after the event.Differences in blood flow velocity between the NAION-affected and control groups were not statistically significant at any time point;however,there was a trend toward increasing blood flow velocity initially after an NAION,with a decrease over time.Conclusions:This study demonstrates the feasibility of retinal function imaging to quantify macular blood flow velocity in patients with acute NAION.There were no statistically significant differences in blood flow velocity detected between NAION-affected eyes and healthy controls at any of the time points examined;however,there was a trend toward an increase in both arteriolar and venular BFV subacutely,then a decrease in the chronic phase after NAION,which could be suggestive of a mechanism of attempted compensation in the setting of acute ischemia.

Evaluation of the effect of myocardial perfusion after percutaneous coronary intervention in coronary artery disease by using intracoronary myocardial contrast echocardiography and two other angiographic techniques

Detection of abnormal myocardial perfusion is crucial to the prognosis of patients with coronary artery disease(CAD)after they have undergone percutaneous coronary intervention(PCI).The objective of this study is to evaluate the effect of myocardial perfusion by three different methods—intra-coronary myocardial contrast echocardiography(ICMCE),corrected thrombolysis in myocardial infarction frame count(CTFC),and coronary blood flow velocity(BFV)—and to determine the value of these different methods in the evaluation of the effect of myocardial perfusion post-PCI.For the study sixty-eight patients were divided into four groups based on selective coronary angiography results:group A(normal coronary artery),group B(75%–95%coronary artery stenosis),group C(coronary artery stenosis>95%)and group D(acute total coronary occlusion).The effect of myocardial reperfusion was evaluated using the above mentioned three methods 15 min after PCI.IC-MCE was also performed before PCI in group D.The quantitative parameters of MCE involved:contrast peak intensity,time to peak intensity and area under the curve,representing myocardial blood volume,reperfusion velocity and myocardial blood flow,respectively.No difference was found in CTFC between the coronary artery stenosis group and the normal group.BFV was slower in group D than in group A(P<0.05).The myocardial blood volume and the myocardial blood flow of the IC-MCE quantitative parameters were markedly lower in group C compared with those in group A(P<0.05),and there were significant differences in the three MCE parameters between group D and group A(P<0.05).For those patients with acute or total occlusion,the levels of myocardial perfusion before and after PCI were similar,as determined by IC-MCE and visually analyzed from 61 segments(P<0.05).Quantitative IC-MCE evaluation of myocardial reperfusion is more accurate than with the other two methods.Moreover,with qualitative IC-MCE the level of myocardial reperfusion can be viewed directly and rapidly.Thus,the IC-MCE method is of great value to coronary artery disease(CAD)patients undergoing PCI,especially for those with acute myocardial infarction(AMI).

A review of functional slit lamp biomicroscopy

Functional slit lamp biomicroscopy(FSLB)is a novel device which consists of a traditional slit-lamp and a digital camera.It can quantitatively assess vessel diameter,blood flow velocity,and blood flow rate and can create noninvasive microvascular perfusion maps(nMPMs).At present,FSLB is mainly used in contact lens(CL)and dry eye disease(DED)studies to advance our understanding of ocular surface microcirculation.FSLB-derived blood flow and vessel density measures are significantly altered in CL wearers and DED patients compared to normal people.These subtle changes in the ocular surface microcirculation may contribute to the monitoring of potential diseases of the body and provide a new way to diagnose dry eye disease.Therefore,this may also indicate that FSLB can be more widely applied in the study of other diseases to reveal the relationship between changes in ocular surface microcirculation and systemic diseases.The purpose of this paper is to summarize the functions of FSLB and the related studies especially in CL and DED.