Assessment of vascular and endothelial function in Kawasaki disease.

BACKGROUND: Kawasaki disease (KD) is an acute febrile vasculitis. Patients with previous KD have increased risk of coronary arterial aneurysms (CAA) and early-onset arteriosclerosis. Endothelial dysfunction is the earliest manifestation of arteriosclerosis. We aimed to explore the endothelial function and clinical characteristics of patients with previous KD. METHODS: In this case-control study, we investigated childhood KD patients, with and without CAA, and a group of healthy controls. We obtained the anthropometric measurements, metabolic markers, vascular ultrasonography evaluating arterial stiffness and flow-mediated dilatation (FMD), and clinical information obtained by reviewing the patients' charts. Continuous variables were compared using non-parametric analyses and categorical variables, using the chi-square or Fisher's exact tests. RESULTS: Seventy KD patients (median current age, 12.95 years; median follow-up duration, 10.88 years) and 14 healthy controls were recruited. FMD was significantly lower in the CAA group (n = 15) than the control group (FMDs: 5.59% [interquartile range, 3.99-6.86%] vs. 7.49% [5.96-9.42%], p = 0.049; diastolic FMD: 6.48% [4.14-7.32%] vs. 7.87% [6.19-9.98%], p = 0.042). The CAA group had a higher percentage of impaired FMD and the significantly largest coronary segments of the three groups. Other parameters including metabolic markers, carotid intima-media thickness, and arterial stiffness were not statistically different. CONCLUSION: KD patients, especially those with CAAs, may have impaired endothelial function. FMD may be a good indicator of endothelial dysfunction for use in long-term follow-up of KD patients.

Volumetric coronary endothelial function assessment: a feasibility study exploiting stack-of-stars 3D cine MRI and image-based respiratory self-gating.

Abnormal coronary endothelial function (CEF), manifesting as depressed vasoreactive responses to endothelial-specific stressors, occurs early in atherosclerosis, independently predicts cardiovascular events, and responds to cardioprotective interventions. CEF is spatially heterogeneous along a coronary artery in patients with atherosclerosis, and thus recently developed and tested non-invasive 2D MRI techniques to measure CEF may not capture the extent of changes in CEF in a given coronary artery. The purpose of this study was to develop and test the first volumetric coronary 3D MRI cine method for assessing CEF along the proximal and mid-coronary arteries with isotropic spatial resolution and in free-breathing. This approach, called 3D-Stars, combines a 6 min continuous, untriggered golden-angle stack-of-stars acquisition with a novel image-based respiratory self-gating method and cardiac and respiratory motion-resolved reconstruction. The proposed respiratory self-gating method agreed well with respiratory bellows and center-of-k-space methods. In healthy subjects, 3D-Stars vessel sharpness was non-significantly different from that by conventional 2D radial in proximal segments, albeit lower in mid-portions. Importantly, 3D-Stars detected normal vasodilatation of the right coronary artery in response to endothelial-dependent isometric handgrip stress in healthy subjects. Coronary artery cross-sectional areas measured using 3D-Stars were similar to those from 2D radial MRI when similar thresholding was used. In conclusion, 3D-Stars offers good image quality and shows feasibility for non-invasively studying vasoreactivity-related lumen area changes along the proximal coronary artery in 3D during free-breathing.

Assessment of the sublingual microcirculation with the GlycoCheck system: Reproducibility and examination conditions.

BACKGROUND: The glycocalyx is an extracellular layer lining the lumen of the vascular endothelium, protecting the endothelium from shear stress and atherosclerosis and contributes to coagulation, immune response and microvascular perfusion. The GlycoCheck system estimates glycocalyx' thickness in vessels under the tongue from perfused boundary region (PBR) and microvascular perfusion (red blood cell (RBC) filling) via a camera and dedicated software. OBJECTIVES: Evaluating reproducibility and influence of examination conditions on measurements with the GlycoCheck system. METHODS: Open, randomised, controlled study including 42 healthy smokers investigating day-to-day, side-of-tongue, inter-investigator variance, intraclass-correlation (ICC) and influence of examination conditions at intervals from 0-180 minutes on PBR and RBC filling. RESULTS: Mean (SD) age was 24.9 (6.1) years, 52% were male. There was no significant intra- or inter-investigator variation for PBR or RBC filling nor for PBR for side-of-tongue. A small day-to-day variance was found for PBR (0.012µm, p = 0.007) and RBC filling (0.003%, p = 0.005) and side-of-tongue, RBC filling (0.025%, p = 0.009). ICC was modest but highly improved by increasing measurements. Small significant influence of cigarette smoking (from 40-180 minutes), high calorie meal intake and coffee consumption was found. The latter two peaking immediately and tapering off but remained significant up to 180 minutes, highest PBR changes for the three being 0.042µm (p<0.05), 0.183µm (p<0.001) and 0.160µm (p<0.05) respectively. CONCLUSIONS: Measurements with the GlycoCheck system have a moderate reproducibility, but highly increases with multiple measurements and a small day-to-day variability. Smoking, meal and coffee intake had effects up to 180 minutes, abstinence is recommended at least 180 minutes before GlycoCheck measurements. Future studies should standardise conditions during measurements.

Post-stEnting assessment of Re-endothelialization with optical Frequency domain imaging aftEr Chronic Total Occlusion procedure: The PERFE-CTO Study Design and Rationale.

BACKGROUND: The treatment of chronic total occlusion of coronary arteries by percutaneous coronary intervention (CTO PCI) is one of the most representative technical advances in ischemic cardiomyopathy of last decade. However, how the complex histopathological remodeling and the new techniques affect healing processes after stent implantation remains unknown. OBJECTIVE: The objective of the PERFE-CTO study is to analyze stent coverage, malapposition and other mechanical abnormalities 3 months after CTO recanalization using intravascular imaging. METHODS: In a French prospective interventional multicenter study, stent strut coverage, acquired malapposition and neointimal hyperplasia (NIH) proliferation will be systematically assessed with 3 months angiogram control and intracoronary optical frequency domain imaging (OFDI) after successful CTO PCI of >20 mm in length. The impact of routine systematical intracoronary imaging after these complex procedures will also be evaluated by measuring the rate of significant mechanical abnormalities (strut malapposition, edge dissection, thrombus) that was undetected by fluoroscopy alone and by complementary PCI when needed. Secondarily, these data will be compared according to clinical characteristics, antiplatelet therapy use or desobstruction technique (antegrade vs. retrograde, true lumen vs. subintima). Each patient will undergo a one-year clinical follow-up. A total of 150 analyzed CTO lesions is expected. CONCLUSION: The PERFE-CTO study will provide essential understanding of the early history after CTO recanalization and the identification of inadequate evolution (stent thrombosis, restenosis or late delayed stent endothelization and cardiovascular outcomes) using intravascular imaging to improve long-term CTO results.

Quantitative assessment of human donor corneal endothelium with Gabor domain optical coherence microscopy.

We report on a pathway for Gabor domain optical coherence microscopy (GD-OCM)-based metrology to assess the donor's corneal endothelial layers ex vivo. Six corneas from the Lions Eye Bank at Albany and Rochester were imaged with GD-OCM. The raw 3-D images of the curved corneas were flattened using custom software to enhance the 2-D visualization of endothelial cells (ECs); then the ECs within a circle of 500-µm-diameter were analyzed using a custom corner method and a cell counting plugin in ImageJ. The EC number, EC area, endothelial cell density (ECD), and polymegethism (CV) were quantified in five different locations for each cornea. The robustness of the method (defined as the repeatability of measurement together with interoperator variability) was evaluated by independently repeating the entire ECD measurement procedure six times by three different examiners. The results from the six corneas show that the current modality reproduces the ECDs with a standard deviation of 2.3% of the mean ECD in every location, whereas the mean ECD across five locations varies by 5.1%. The resolution and imaging area provided through the use of GD-OCM may help to ultimately better assess the quality of donor corneas in transplantation.

Endothelialization of an Amplatzer Septal Occluder Device 6 Months Post Implantation: Is This Enough Time? An In Vivo Angioscopic Assessment.

The current guidelines recommend a minimum of 6 months of antithrombotic and antibiotic prophylaxis following septal occluding device placement for transcatheter closure of atrial septal defect. Full neoendothelialization is thought to be completed within 6 months of device implantation; however, there is no method available that can assess the level of neoendothelialization in vivo. This report therefore evaluates endothelialization in vivo and demonstrates that 6 months of postimplantation prophylactic therapy may not provide sufficient time for adequate endothelialization. Further investigations are warranted to determine the optimal duration of these treatments after atrial septal defect closure.

New assessment of endothelial function measured by short time flow-mediated vasodilation: Comparison with conventional flow-mediated vasodilation measurement.

BACKGROUND: Measurement of flow-mediated vasodilation (FMD) is an established method for assessing endothelial function. Measurement of FMD is useful for showing the relationship between atherosclerosis and endothelial function, mechanisms of endothelial dysfunction, and clinical implications including effects of interventions and cardiovascular events. To shorten and simplify the measurement of FMD, we have developed a novel technique named short time FMD (stFMD). We investigated the validity of stFMD for assessment of endothelial function compared with conventional FMD. METHODS AND RESULTS: We evaluated stFMD and conventional FMD in 82 subjects including patients with atherosclerotic risk factors and cardiovascular disease (66 men and 16 women, 57 ±â€¯16 years). Both stFMD and conventional FMD were significantly correlated with age, systolic blood pressure, diastolic blood pressure and baseline brachial artery diameter. In addition, stFMD was significantly correlated with conventional FMD (r = 0.76, P < 0.001). Bland-Altman plot analysis showed good agreement b etween stFMD and conventional FMD. Moreover, stFMD in the at risk group and that in the cardiovascular disease group were significantly lower than that in the no risk group (4.6 ±â€¯2.3% and 4.4 ±â€¯2.2% vs. 7.3 ±â€¯1.9%, P < 0.001, respectively). Optimal cutoff value of stFMD for diagnosing atherosclerosis was 7.0% (sensitivity of 71.0% and specificity of 85.0%). CONCLUSIONS: These findings suggest that measurement of stFMD, a novel and simple method, is useful for assessing endothelial function. Measurement of stFMD may be suitable for screening of atherosclerosis when repeated measurements of vascular function are required and when performing a clinical trial using a large population. CLINICAL TRIAL REGISTRATION INFORMATION: URL for Clinical Trial: http://UMIN; Registration Number for Clinical Trial: UMIN000025458.

Reactive hyperemia-peripheral arterial tonometry is useful for assessment of not only endothelial function but also stenosis of the digital artery.

BACKGROUND: Although reactive hyperemia-peripheral arterial tonometry (RH-PAT) is widely used for assessment of endothelial function, RH index (RHI) cannot be measured in some cases when pulse wave amplitude (PWA) is very low. Decrease in PWA is mainly caused by proper palmar digital artery (PPDA) stenosis. The purpose of this study was to evaluate the relationship between PWA measured by RH-PAT and stenosis of the PPDA measured by digital subtraction angiography and to evaluate the limitation of assessment of endothelial function measured by RHI in patients with PPDA stenosis. METHODS: We measured baseline PWA in 51 fingers including the first to third fingers of both hands in 10 patients who had PPDA stenosis and in 66 fingers that were the first fingers of both hands in 33 subjects who had no PPDA stenosis. Severe stenosis was defined as over 75% by lower percent diameter stenosis between two PPDAs in a finger. RESULTS: PWA was significantly correlated with stenosis of the digital artery (r=-0.55; P<0.0001). A PWV value of 300mV was the optimal cut-off value for severe stenosis (sensitivity, 84.0%; specificity, 88.5%). Log RHI was significantly lower in patients with PPDA stenosis than in subjects without PPDA stenosis (0.33±0.27 versus 0.73±0.27, P=0.007). CONCLUSIONS: RH-PAT may be useful for assessment of not only endothelial function but also PPDA stenosis. RHI may be underestimated in patients with PPDA stenosis. We should pay attention to low baseline PWA when measuring RHI. CLINICAL TRIAL REGISTRATION INFORMATION: URL for clinical trial: http://UMIN; registration number for clinical trial: UMIN000003409.

Imaging the myocardial ischemic cascade.

Non-invasive imaging plays a growing role in the diagnosis and management of ischemic heart disease from its earliest manifestations of endothelial dysfunction to myocardial infarction along the myocardial ischemic cascade. Experts representing the North American Society for Cardiovascular Imaging and the European Society of Cardiac Radiology have worked together to organize the role of non-invasive imaging along the framework of the ischemic cascade. The current status of non-invasive imaging for ischemic heart disease is reviewed along with the role of imaging for guiding surgical planning. The issue of cost effectiveness is also considered. Preclinical disease is primarily assessed through the coronary artery calcium score and used for risk assessment. Once the patient becomes symptomatic, other imaging tests including echocardiography, CCTA, SPECT, PET and CMR may be useful. CCTA appears to be a cost-effective gatekeeper. Post infarction CMR and PET are the preferred modalities. Imaging is increasingly used for surgical planning of patients who may require coronary artery bypass.

Reproducibility and agreement of different non-invasive methods of endothelial function assessment.

Flow-mediated dilatation (FMD) is an established, but investigator-demanding method, used to non-invasively determine nitric oxide (NO)-dependent endothelial function in humans. Local thermal hyperemia (LTH) or post-occlusive reactive hyperemia (PORH) of the skin measured with a laser Doppler flow imager may be a less demanding alternative of FMD. We investigated the reproducibility of the different measures of vascular function, their interrelationship and the NO-dependency of LTH. Measurements were performed twice in 27 healthy men (8 smokers), one week apart. Local application of NG-monomethyl-l-arginine (L-NMMA) by means of iontophoresis was used to determine the NO-dependency of LTH. Using L-NMMA, the peak and plateau responses of LTH were reduced by 31% (p < .001) and 65% (<0.001), respectively. For all measurements the coefficient of variation (CV) was higher in smokers than in non-smokers. For non-smokers the CV of FMD was 12%, of LTH peak response 17%, of LTH plateau response 12%, of PORH peak response 14% and of PORH area under the curve response 11%. FMD correlated weakly with the PORH peak and area under the curve response (r = 0.39 and 0.43, p < .05), whereas the LTH-plateau response correlated with the PORH peak response (r = 0.68, p < .01) in non-smokers, but FMD and LTH peak or plateau responses were unrelated. In conclusion, the LTH plateau response is for two-third NO-dependent, but unrelated to FMD. Furthermore, despite easy to perform the LTH responses are not more reproducible than FMD. Given the weak associations, the different methods of vascular function assessment are not interchangeable.

Self-gated golden angle spiral cine MRI for coronary endothelial function assessment.

PURPOSE: Depressed coronary endothelial function (CEF) is a marker for atherosclerotic disease, an independent predictor of cardiovascular events, and can be quantified non-invasively with ECG-triggered spiral cine MRI combined with isometric handgrip exercise (IHE). However, MRI-CEF measures can be hindered by faulty ECG-triggering, leading to prolonged breath-holds and degraded image quality. Here, a self-gated golden angle spiral method (SG-GA) is proposed to eliminate the need for ECG during cine MRI. METHODS: SG-GA was tested against retrospectively ECG-gated golden angle spiral MRI (ECG-GA) and gold-standard ECG-triggered spiral cine MRI (ECG-STD) in 10 healthy volunteers. CEF data were obtained from cross-sectional images of the proximal right and left coronary arteries in a 3T scanner. Self-gating heart rates were compared to those from simultaneous ECG-gating. Coronary vessel sharpness and cross-sectional area (CSA) change with IHE were compared among the 3 methods. RESULTS: Self-gating precision, accuracy, and correlation-coefficient were 7.7 ± 0.5 ms, 9.1 ± 0.7 ms, and 0.93 ± 0.01, respectively (mean ± standard error). Vessel sharpness by SG-GA was equal or higher than ECG-STD (rest: 63.0 ± 1.7% vs. 61.3 ± 1.3%; exercise: 62.6 ± 1.3% vs. 56.7 ± 1.6%, P < 0.05). CSA changes were in agreement among the 3 methods (ECG-STD = 8.7 ± 4.0%, ECG-GA = 9.6 ± 3.1%, SG-GA = 9.1 ± 3.5%, P = not significant). CONCLUSION: CEF measures can be obtained with the proposed self-gated high-quality cine MRI method even when ECG is faulty or not available. Magn Reson Med 80:560-570, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

A phantom study to determine the theoretical accuracy and precision of radial MRI to measure cross-sectional area differences for the application of coronary endothelial function assessment.

PURPOSE: MRI has been used to noninvasively assess coronary endothelial function by measuring the vasoreactivity in response to handgrip exercise. However, the spatial resolution of MRI is limited relative to the expected vasodilation response of healthy coronary arteries (10%-20%), and the sensitivity of MRI to detect such small cross-sectional area differences has yet to be quantitatively examined. METHODS: Holes of different diameters were drilled in a phantom to simulate a range of physiological responses of coronary arteries to stress. Radial cine MR images with different spatial resolutions were acquired under moving conditions, and different noise levels were simulated. Cross-sectional areas were automatically measured and statistically analyzed to quantify the smallest detectable area difference. RESULTS: Statistical analyses suggest that radial MRI is capable of distinguishing area differences of 0.2 to 0.3 mm2 for high signal-to-noise ratio images, which correspond to a percentage coronary area difference of 3% to 4% for a 3-mm baseline diameter. Furthermore, the smallest detectable area difference was largely independent of the pixel size for the sequence and range of diameters investigated in this study. CONCLUSION: Radial MRI is capable of reliably detecting small differences in cross-sectional areas that are well within the expected physiological range of stress-induced area changes in of healthy coronary arteries. Magn Reson Med 79:108-120, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Assessment of an engineered endothelium via single-photon emission computed tomography.

The clinical translation of cell-based therapeutics often requires highly sensitive, non-invasive imaging tools to assess cell function and distribution in vivo. The objective of this research was to determine whether human Sodium-Iodide Symporter (hNIS) ectopic expression in endothelial cells (ECs) in combination with single-photon emission computed tomography (SPECT) is a feasible approach to non-invasively monitor the presence and viability of an engineered endothelium on expanded polytetrafluoroethylene (ePTFE). Human umbilical vein endothelial cells (HUVECs) were transduced with pLL3.7-hNIS via lentivirus with multiplicity of infection (MOI) of 0, 2, 5, and 10 (n = 4). Ectopic expression of hNIS in HUVECs via optimized lentiviral transduction (MOI 5) enabled cell uptake of a radioisotope that can be detected by SPECT without affecting endothelial cell viability, oxidative stress, or antithrombogenic functions. The viability and distribution of an engineered endothelium grown on ePTFE coated with the biodegradable elastomer poly(1, 8 octamethylene citrate) (POC) and exposed to fluid flow was successfully monitored non-invasively by SPECT. We report the feasibility of a non-invasive, highly sensitive and functional assessment of an engineered endothelium on ePTFE using a combination of SPECT and X-ray computed tomography (SPECT/CT) imaging and hNIS ectopic expression in ECs. This technology potentially allows for the non-invasive assessment of transplanted living cells in vascular conduits. Biotechnol. Bioeng. 2017;114: 2371-2377. © 2017 Wiley Periodicals, Inc.

Assessment of microvascular endothelial function in type 1 diabetes using laser speckle contrast imaging.

OBJECTIVE: To test whether laser speckle contrast imaging (LSCI) coupled with physiological post-occlusive reactive hyperemia (PORH) and pharmacological iontophoresis of acetylcholine (ACh) as local vasodilator stimuli could distinguish between cutaneous microvascular responses of Type 1 Diabetes (T1DM)'s patients with endothelial dysfunction and that of healthy controls. METHODS: Patients with T1DM aged ≥12years completed a clinical-epidemiological questionnaire. Data detailing patients' such as daily insulin dose, duration of diabetes, and use of pharmaceuticals such as antihypertensive drugs and statins that could interfere with endothelial function were obtained. Vascular reactivity was assessed in the forearm by LSCI and PORH at baseline and during iontophoresis of ACh using increasing anodic currents of 30, 60, 90, 120, 150 and 180µA in 10second intervals. RESULTS: This study included 50 patients with T1DM and 30 control subjects. The mean resting flux did not differ between patients and control subjects. T1DM patients exhibited endothelial dysfunction upon challenge with physiological or pharmacological stimuli. The microvascular response to both ACh and PORH (i.e., maximum response at peak and amplitude) were significantly reduced in patients with diabetes compared with control subjects (p<0.001). CONCLUSION: We demonstrated that endothelium-dependent skin microvascular vasodilator responses are significantly impaired in patients with T1DM compared to healthy subjects investigated using LSCI coupled with ACh iontophoresis and PORH. Additionally, we find that LSCI is a promising methodology for studying physiological vascular reactivity in T1DM.

Assessment of endothelial shear stress in patients with mild or intermediate coronary stenoses using coronary computed tomography angiography: comparison with invasive coronary angiography.

Characterization of endothelial shear stress (ESS) may allow for prediction of the progression of atherosclerosis. The aim of this investigation was to develop a non-invasive approach for in vivo assessment of ESS by coronary computed tomography angiography (CTA) and to compare it with ESS derived from invasive coronary angiography (ICA). A total of 41 patients with mild or intermediate coronary stenoses who underwent both CTA and ICA were included in the analysis. Two geometrical models of the interrogated vessels were reconstructed separately from CTA and ICA images. Subsequently, computational fluid dynamics were applied to calculate the ESS, from which ESSCTA and ESSICA were derived, respectively. Comparisons between ESSCTA and ESSICA were performed on 163 segments of 57 vessels in the CTA and ICA models. ESSCTA and ESSICA were similar: mean ESS: 4.97 (4.37-5.57) Pascal versus 4.86 (4.27-5.44) Pascal, p = 0.58; minimal ESS: 0.86 (0.67-1.05) Pascal versus 0.79 (0.63-0.95) Pascal, p = 0.37; and maximal ESS: 14.50 (12.62-16.38) Pascal versus 13.76 (11.44-16.08) Pascal, p = 0.44. Good correlations between the ESSCTA and the ESSICA were observed for the mean (r = 0.75, p < 0.001), minimal (r = 0.61, p < 0.001), and maximal (r = 0.62, p < 0.001) ESS values. In conclusion, geometrical reconstruction by CTA yields similar results to ICA in terms of segment-based ESS calculation in patients with low and intermediate stenoses. Thus, it has the potential of allowing combined local hemodynamic and plaque morphologic information for risk stratification in patients with coronary artery disease.

Assessment of macrovascular endothelial function using pulse wave analysis and its association with microvascular reactivity in healthy subjects.

BACKGROUND: Pulse wave analysis (PWA) and laser Doppler fluximetry (LDF) are non-invasive methods of assessing macrovascular endothelial function and microvascular reactivity respectively. The aim of this study was to assess the correlation between macrovascular endothelial function assessed by PWA and microvascular reactivity assessed by LDF. METHOD: 297 healthy and non-smoking subjects (159 females, mean age (±SD) 23.56 ± 4.54 years) underwent microvascular reactivity assessment using LDF followed by macrovascular endothelial function assessments using PWA. RESULTS: Pearson's correlation showed no correlation between macrovascular endothelial function and microvascular reactivity (r = -0.10, P = 0.12). CONCLUSION: There was no significant correlation between macrovascular endothelial function assessed by PWA and microvascular reactivity assessed by LDF in healthy subjects.

A novel effective method for the assessment of microvascular function in male patients with coronary artery disease: a pilot study using laser speckle contrast imaging.

Evaluation of microvascular endothelial function is essential for investigating the pathophysiology and treatment of cardiovascular and metabolic diseases. Although laser speckle contrast imaging technology is well accepted as a noninvasive methodology for assessing microvascular endothelial function, it has never been used to compare male patients with coronary artery disease with male age-matched healthy controls. Thus, the aim of this study was to determine whether laser speckle contrast imaging could be used to detect differences in the systemic microvascular functions of patients with established cardiovascular disease (n=61) and healthy age-matched subjects (n=24). Cutaneous blood flow was assessed in the skin of the forearm using laser speckle contrast imaging coupled with the transdermal iontophoretic delivery of acetylcholine and post-occlusive reactive hyperemia. The maximum increase in skin blood flow induced by acetylcholine was significantly reduced in the cardiovascular disease patients compared with the control subjects (74 vs 116%; P<0.01). With regard to post-occlusive reactive hyperemia-induced vasodilation, the patients also presented reduced responses compared to the controls (0.42±0.15 vs 0.50±0.13 APU/mmHg; P=0.04). In conclusion, laser speckle contrast imaging can identify endothelial and microvascular dysfunctions in male individuals with cardiovascular disease. Thus, this technology appears to be an efficient non-invasive technique for evaluating systemic microvascular and endothelial functions, which could be valuable as a peripheral marker of atherothrombotic diseases in men.

Retrospectively gated MRI for in vivo assessment of endothelium-dependent vasodilatation and endothelial permeability in murine models of endothelial dysfunction.

Endothelial dysfunction is linked to impaired endothelial-dependent vasodilatation and permeability changes. Here, we quantify both of these phenomena associated with endothelial dysfunction by MRI in vivo in mice. Endothelial function was evaluated in the brachiocephalic artery (BCA) and left carotid artery (LCA) in ApoE/LDLR(-/-) and high-fat diet (HFD)-fed mice as compared with control mice (C57BL/6J). The 3D IntraGate® FLASH sequence was used for evaluation of changes in vessels' cross-sectional area (CSA) and volume following acetylcholine (Ach) administration. Evaluation of endothelial permeability after administration of contrast agent (Galbumin, BioPAL) was based on the variable flip angle method for the assessment of parameters based on the relaxation time (T1 ) value. In order to confirm the involvement of nitric oxide (NO) in response to Ach, L-NAME-treated mice were also analyzed. To confirm that endothelial permeability changes accompany the impairment of Ach-dependent vasodilatation, permeability changes were analyzed in isolated, perfused carotid artery. In C57BL/6J mice, Ach-induced vasodilatation led to an approximately 25% increase in CSA in both vessels, which was temporarily dissociated from the effect of Ach on heart rate. In ApoE/LDLR(-/-) or HFD-fed mice Ach induced a paradoxical vasoconstriction that amounted to approximately 30% and 50% decreases in CSA of BCA and LCA respectively. In ApoE/LDLR(-/-) and HFD-fed mice endothelial permeability in BCA was also increased (fall in T1 by about 25%). In L-NAME-treated mice Ach-induced vasodilatation in BCA was lost. In isolated, perfused artery from ApoE/LDLR(-/-) mice endothelial permeability was increased. MRI-based assessment of endothelium-dependent vasodilatation induced by Ach and endothelial permeability using a retrospectively self-gated 3D gradient-echo sequence (IntraGate® FLASH) enables the reliable detection of systemic endothelial dysfunction in mice and provides an important tool for the experimental pharmacology of the endothelium in murine models of diseases in vivo. Copyright © 2016 John Wiley & Sons, Ltd.

Ultrasound Assessment of Endothelial Function: A Technical Guideline of the Flow-mediated Dilation Test.

Cardiovascular disease is the primary cause of mortality and a major cause of disability worldwide. The dysfunction of the vascular endothelium is a pathological condition characterized mainly by a disruption in the balance between vasodilator and vasoconstrictor substances and is proposed to play an important role in the development of atherosclerotic cardiovascular disease. Therefore, a precise evaluation of endothelial function in humans represents an important tool that could help better understand the etiology of multiple cardio-centric pathologies. Over the past twenty-five years, many methodological approaches have been developed to provide an assessment of endothelial function in humans. Introduced in 1989, the FMD test incorporates a forearm occlusion and subsequent reactive hyperemia that promotes nitric oxide production and vasodilation of the brachial artery. The FMD test is now the most widely utilized, non-invasive, ultrasonic assessment of endothelial function in humans and has been associated with future cardiovascular events. Although the FMD test could have clinical utility, it is a physiological assessment that has inherited several confounding factors that need to be considered. This article describes a standardized protocol for determining FMD including the recommended methodology to help minimize the physiological and technical issues and improve the precision and reproducibility of the assessment.

Assessment of endothelial function and myocardial flow reserve using (15)O-water PET without attenuation correction.

PURPOSE: Myocardial blood flow (MBF) measurement using positron emission tomography (PET) from the washout rate of (15)O-water is theoretically independent of tissue attenuation. The aim of this study was to evaluate the impact of not using attenuation correction in the assessment of coronary endothelial function and myocardial flow reserve (MFR) using (15)O-water PET. METHODS: We retrospectively processed 70 consecutive (15)O-water PET examinations obtained at rest and during cold pressor testing (CPT) in patients with dilated cardiomyopathy (n = 58), or at rest and during adenosine infusion in heart transplant recipients (n = 12). Data were reconstructed with attenuation correction (AC) and without attenuation correction (NAC) using filtered backprojection, and MBF was quantified using a single compartmental model. The agreement between AC and NAC data was assessed using Lin's concordance correlation coefficient followed by Bland-Altman plot analysis. RESULTS: Regarding endothelial function, NAC PET showed poor reproducibility and poor agreement with AC PET data. Conversely, NAC PET demonstrated high reproducibility and a strong agreement with AC PET for the assessment of MFR. CONCLUSION: Non-attenuation-corrected (15)O-water PET provided an accurate measurement of MFR compared to attenuation-corrected PET. However, non-attenuation-corrected PET data were less effective for the assessment of endothelial function using CPT in this population.