Microvascular Assessment Research Articles

Macrovascular blood flow and microvascular cerebrovascular reactivity are regionally coupled in adolescence.

Cerebrovascular imaging assessments are particularly challenging in adolescent cohorts, where not all modalities are appropriate, and rapid brain maturation alters hemodynamics at both macro- and microvascular scales. In a preliminary sample of healthy adolescents (n=12, 8-25 years), we investigated relationships between 4D flow MRI-derived blood velocity and blood flow in bilateral anterior, middle, and posterior cerebral arteries and BOLD cerebrovascular reactivity in associated vascular territories. As hypothesized, higher velocities in large arteries are associated with an earlier response to a vasodilatory stimulus (cerebrovascular reactivity delay) in the downstream territory. Higher blood flow through these arteries is associated with a larger BOLD response to a vasodilatory stimulus (cerebrovascular reactivity amplitude) in the associated territory. These trends are consistent in a case study of adult moyamoya disease. In our small adolescent cohort, macrovascular-microvascular relationships for velocity/delay and flow/CVR change with age, though underlying mechanisms are unclear. Our work emphasizes the need to better characterize this key stage of human brain development, when cerebrovascular hemodynamics are changing, and standard imaging methods offer limited insight into these processes. We provide important normative data for future comparisons in pathology, where combining macro- and microvascular assessments may better help us prevent, stratify, and treat cerebrovascular disease.

Coronary angiography-derived microvascular assessment (IMR angio ) in patients with amyloidosis: a first US report.

Coronary angiography-derived microvascular assessment (IMR angio ) in patients with amyloidosis: a first US report.

400.06 - Coronary Angiography-Derived Microvascular Assessment (IMRangio) in Patients With Amyloidosis: First US Report of IMRangio

400.06 - Coronary Angiography-Derived Microvascular Assessment (IMRangio) in Patients With Amyloidosis: First US Report of IMRangio

Pilot Assessment of Piezoelectric Transducers as a Cost-Effective Alternative to EndoPAT

Introduction: Current microvascular assessments may not be practical or accessible requiring experienced personnel and/or ongoing equipment costs. Piezoelectric transducers can reliably obtain finger blood pressure waves, similar to peripheral arterial tonometry devices; thus, they could be used to estimate microvascular function. We aimed to validate piezoelectric transducers as an alternative measure of microvascular function compared to EndoPAT. Methods: Twenty-five adults (aged 20–64 years) completed reactive hyperemia (5 min forearm circulatory occlusion and 3 min recovery) with piezoelectric transducers on the middle fingers and EndoPAT probes on the index fingers. Average area under the curve (AUC) of the pulse wave signal for the occluded and control arms was determined at baseline, every 30 s post-occlusion, and 10 s around the peak response. Microvascular function index (MFI) was calculated as the ratio of AUC post-occlusion to AUC baseline in the test arm, then normalized to the same ratio in the control arm. MFI at each time point was correlated with the reactive hyperemia index (RHI) from the EndoPAT. Results: The greatest significance was found between RHI and MFI at 10 s around the peak response (Spearman’s r = 0.67, p = 0.0002; Pearson’s r = 0.76, p = 0.00001). Conclusion: MFI is a reusable and user-friendly microvascular function assessment that could provide better access to vascular health screening.

Vascular feature identification in actinic keratosis grades I-III using dynamic optical coherence tomography with automated, quantitative analysis

Clinical grading of actinic keratosis (AK) is based on skin surface features, while subclinical alterations are not taken into consideration. Dynamic optical coherence tomography (D-OCT) enables quantification of the skin´s vasculature, potentially helpful to improve the link between clinical and subclinical features. We aimed to compare microvascular characteristics across AK grades using D-OCT with automated vascular analysis. This explorative study examined AK and photodamaged skin (PD) on the face or scalp. AKs were clinically graded according to the Olsen Classification scheme before D-OCT assessment. Using an open-source software tool, the OCT angiographic analyzer (OCTAVA), we quantified vascular network features, including total and mean vessel length, mean vessel diameter, vessel area density (VAD), branchpoint density (BD), and mean tortuosity from enface maximum intensity projection images. Additionally, we performed subregional analyses on selected scans to overcome challenges associated with imaging through hyperkeratosis (each lesion group; n = 18). Our study included 45 patients with a total of 205 AKs; 93 grade I lesions, 65 grade II, 47 grade III and 89 areas with PD skin. We found that all AK grades were more extensively vascularized relative to PD, as shown by greater total vessel length and VAD (p ≤ 0.009). Moreover, AKs displayed a disorganized vascular network, with higher BD in AK I-II (p < 0.001), and mean tortuosity in AK II-III (p ≤ 0.001) than in PD. Vascularization also increased with AK grade, showing significantly greater total vessel length in AK III than AK I (p = 0.029). Microvascular quantification of AK unveiled subclinical, quantitative differences among AK grades I-III and PD skin. D-OCT-based microvascular assessment may serve as a supplement to clinical AK grading, potentially raising perspectives to improve management strategies.

Imaging of the vascular distribution of the outer ear using optical coherence tomography angiography for highly accurate positioning of a hearable sensor.

Novel hearable technology is securely and comfortably positioned within the ear canal minimizing inaccuracies caused by accessory movements during activities. Despite extensive research on hearable technologies within the outer ear, there is a lack of research in the field of vascular imaging and quantitative analysis in the outer ear in vivo, which is one of the crucial factors to select the appropriate sensor position. Therefore, in this paper, we introduced optical coherence tomography angiography (OCTA)-based qualitative and quantitative analyses to visualize the inner vasculature of the outer ear to acquire vascular maps for microvascular assessments in vivo. By generating maximum amplitude projection images from three-dimensional blood vascular volume, we identified variations of blood vessel signal caused by the different biological characteristics and curvature of the ear among individuals. The performance of micro-vascular mapping using the proposed method was validated through the comparison and analysis of individual vascular parameters using extracted 20 vascular-related variables. In addition, we extracted pulsatile blood flow signals, demonstrating its potential to provide photoplethysmographic signals and ear blood maps simultaneously. Therefore, our proposed OCTA-based method for ear vascular mapping successfully provides quantitative information about ear vasculature, which is potentially used for determining the position of system-on-chip sensors for health monitoring in hearable devices.

Comparing planned versus ad hoc coronary microvascular assessment: Early findings from the Coronary Microvascular Disease Registry

BackgroundCoronary microvascular dysfunction (CMD) is an etiology for angina with non-obstructive coronary disease. However, the initial adoption of CMD assessment, whether planned or conducted ad hoc, is limited. We characterize planned and ad hoc CMD assessments and highlight evolving trends of a CMD referral center. MethodsWe analyzed outpatient data from the Coronary Microvascular Disease Registry from 2021 to 2023. Patients were categorized into planned or ad hoc CMD assessment groups, and baseline characteristics, hospital stay, medications, and physiological measurements were compared. Secondary analysis evaluated a CMD referral center's evolution. ResultsOf 101 included outpatients, 67.3 % underwent ad hoc procedures and 32.7 % planned procedures. Average age was 63.1 ± 10.1 years. The planned procedure group was 87.9 % female, and the ad hoc procedure group was 51.5 % female. There were no significant differences in index of microvascular resistance or coronary flow reserve between groups. Hospital stay duration was <1 day for both groups, and neither reported complications. Ad hoc patients were more frequently prescribed aspirin before (64.7 % vs. 36.4 %, p = 0.007) and after the procedure (66.2 % vs. 39.4 %, p = 0.01). CMD rates were higher for planned procedures (30.3 % vs. 10.3 %, p = 0.01). We observed that CMD referral centers have more planned procedures and a higher rate of positive results over time. ConclusionCMD referral centers' planned procedures, and subsequent positive cases, increased over time. This emphasizes the importance of planned procedures, appropriate patient selection, and increased awareness of CMD among healthcare providers. Clinical trial registrationCoronary Microvascular Disease (CMD) Registry, NCT05960474, https://clinicaltrials.gov/study/NCT05960474

Retinal oximetry and microvascular assessment after hypertensive pregnancy complications.

Women with hypertensive disorders of pregnancy (HDP) are at increased risk of developing premature cardiovascular disease (CVD). The mechanisms behind this are not fully understood, but microvascular alterations have been documented in retinal arterioles and venules. The aim of this study was to use non-invasive retinal imaging to investigate the structural and functional properties of arterioles, venules and capillaries in this patient group. We examined 27 women with previous HDP and 23 controls at 3 years postpartum. The retinal microvasculature was assessed by vessel calibre measurements, retinal oximetry and optical coherence tomography angiography. Differences were analysed using non-parametric tests and multiple regression analyses, adjusted for age and body mass index. Median arteriolar oxygen saturation (SaO2; 94.2% vs. 93.0%), venular oxygen saturation (SvO2; 60.1% vs. 62.4%) and arteriovenous saturation difference (AV-difference; 32.8% vs. 32.3%) were similar across groups. Capillary vessel density (VD; 46.2% vs. 46.3%), skeletonised VD (VSD; 21.3 vs. 21.1 mm/mm2) and vessel diameter index (21.65 vs. 21.86) were also comparable. In the HDP group, mean arterial pressure (MAP) was positively correlated with AV-difference (R2 = 0.209) and negatively correlated with arteriolar diameter (CRAE; r2 = 0.382). Structural microvascular alterations appear not to be key biomarkers for CVD risk after HDP as early as 3 years postpartum in otherwise healthy women. Further studies are needed to evaluate whether such changes occur later in life. MAP was associated with AV-difference only in the HDP group, suggesting specific mechanisms affecting functional microvascular properties in these women.

Intra-coronary physiology in contemporary percutaneous coronary intervention and anginal therapy with a focus on microvascular disease

Coronary physiological measurements have transformed the treatment of coronary artery disease (CAD), with increasing evidence supporting the use of pressure wire guided revascularisation. Advances in microvascular assessment have enabled clinicians to discern angina aetiology even in patients without obstructive epicardial coronary artery disease, paving the way for more effective tailored therapy. In this article, the authors will examine pressure wire indices, their role in influencing clinical outcomes and future directions.

Angiography-based coronary microvascular assessment with and without intracoronary pressure measurements: a systematic review.

In recent years, several indices have been proposed for quantifying coronary microvascular resistance. We intended to conduct a comprehensive review that systematically evaluates indices of microvascular resistance derived from angiography. The objective of this study was to identify and analyze angiography-derived indices of microvascular resistance that have been validated against an invasive reference method. We aimed to compare their limits of agreement with their reference methods and explore their advantages and inherent limitations. We searched PubMed from inception until 2022 for studies on different techniques for quantifying microvascular resistance. Seven studies met the inclusion criteria. Five studies included techniques that applied calculations based solely on invasive angiography, and were validated against invasively measured thermodilution-derived index of microvascular resistance. The remaining two studies combined angiography with invasively measured intracoronary pressure data, and were validated against invasive Doppler measurements. We converted the ± 1.96 standard deviation limits of agreement with the reference method from the seven studies into percentages relative to the cut-off value of the reference method. The lower limits of agreement for angiography-based methods ranged from - 122 to - 60%, while the upper limits ranged from 74 to 135%. The range of the limits of agreement was considerably lower for the two combined angiography- and pressure-based methods, standing at - 52 to 60% and - 25 to 27%. Our findings suggest that combined angiography- and pressure-based methods provide a more reliable assessment of microvascular resistance compared to methods relying solely on angiography. Central illustration. Comparative assessment of image-based methods quantifying microvascular resistance with and without intracoronary pressure measurements. Angiography-based methods rely on angiography alone to calculate the microvascular resistance by utilizing angiographic frame counting to extrapolate coronary flow (Q) and subsequently deriving distal coronary pressure using fluid dynamic equations. Combined angiography- and pressure-based methods utilize invasive intracoronary pressure gradients measured during rest and maximal vasodilation to determine coronary flow in their calculation of microvascular resistance. The combined methods showed more acceptable levels of agreement with their reference methods compared to angiography-based methods alone.

In vivo validation of intra-coronary absolute flow measurements and comparison of reliability between different microvascular indices and the microvascular resistance reserve

Abstract Background Coronary microvascular dysfunction plays a major role in patients with cardiac ischemia without flow limiting epicardial coronary stenosis, takotsubo cardiomyopathy, aortic valve stenosis and heart failure with preserved ejection fraction. In clinical practice, the index of microvascular resistance (IMR) and coronary flow reserve (CFR), and more recently the absolute coronary blood flow (ABF), absolute coronary resistance (ACR) and the microvascular resistance reserve (MRR) are used as parameters to measure resistance and flow using continuous coronary thermodilution. Purpose Firstly, to validate ABF measured with continuous coronary thermodilution in vivo against epicardial doppler-measured flow. Secondly, to assess reliability and reproducibility in-vivo of different microvascular indices. Methods For the purpose of this study coronary measurements were conducted in two large animal models and in patients, all with the appropriate ethical committee approval. For the first part of the study, fourteen sheep underwent repeated paired measurements of ABF and ACR (with use of continuous thermodilution) with different saline infusion speeds, as well as IMR, CFR and MRR in multiple coronary vessels. Seven additional sheep underwent these measurements while having simultaneous measurements with epicardial coronary flow probes (gold standard) in an open-chest model. The epicardial flow probes were placed on the proximal left anterior descending and circumflex artery. Maximal hyperemia was induced with adenosine (CFR and IMR) or infusion of saline at a rate of 30ml/min (ABF, ACR and MRR). For the second part of the study, in 41 patients receiving routine microvascular assessment, IMR and CFR measurements were duplicated by a single operator, after re-calibration, to assess the reproducibility of the measurement. The combined animal and human data resulted in the analysis of 408 coronary measurements made in 88 coronary vessels during 65 heart catheterizations. Results In sheep, ABF measured with continuous thermodilution (with saline infusion speeds from 5ml/min to 30ml/min) was accurate when compared with epicardial flow measurements. (Table 1, Fig 1A) Notably, the continuous thermodilution measurement had the tendency to slightly overestimate ABF. (Table 1, Fig 1B) The two methods were equivalent within 15% (Two one-sided test: mean difference: -8.73%; 95% CI: -14.40 to -3.06%, p= 0.016). When comparing test-retest reproducibility between the indices, CFR performed the worst while ACR and MRR performed the best. MRR had a significantly better reproducibility than the IMR. (Table 1, Fig 1C). Conclusion ABF can accurately be determined by continuous coronary thermodilution. MRR and ACR have a significantly superior reliability and reproducibility compared to IMR and CFR. Unlike ACR, MRR is not vessel or territory-size dependent and is therefore the index of choice for future research and clinical assessment of the microcirculation.

RETINAL MICROVASCULAR CHANGES AND RISK OF CORONARY HEART DISEASE: A Systematic Review and Meta-Analysis.

To quantify associations between various retinal microvascular changes and the risk of the development of coronary heart disease (CHD). PubMed, Embase, Web of Science, and Cochrane Library databases were searched for cohort studies on the association between retinal microvascular changes and incident CHD up to July 31, 2023. The summary risk estimates were estimated using the random-effects model. Subgroup and sensitivity analyses were performed to investigate the potential source of heterogeneity. The authors identified 21 studies that met the inclusion criteria of this meta-analysis through database searching. This study yielded significant associations between retinal microvascular changes, including arteriolar narrowing, venular widening, vessel occlusion, and other retinal vascular signs, and the risk of CHD, with pooled adjusted hazard ratios of 1.20 (95% confidence interval: 1.13-1.27). In sex- and age-stratified analyses, retinal microvascular changes were associated with a greater risk of developing CHD in female patients and younger adults. A range of retinal microvascular changes was associated with the risk of CHD, particularly in female patients and younger ages. The results of this study support the concept that retinal microvascular abnormalities may be markers for future CHD. Noninvasive retinal microvascular assessments may be helpful in screening patients with increased CHD risk.

TCT-23 Comparison of Reliability Between Current Indices for Microvascular Assessment and the New Microvascular Resistance Reserve Using Continuous Coronary Thermodilution

TCT-23 Comparison of Reliability Between Current Indices for Microvascular Assessment and the New Microvascular Resistance Reserve Using Continuous Coronary Thermodilution

Four of Five Patients With Chest Pain and Non-Obstructive Coronary Artery Disease who had a Microvascular Assessment had Microvascular Angina

Patients with chest pain and non-obstructive coronary artery disease (NOCAD) may have microvascular disease. Measurement of the index of microcirculatory resistance (IMR) with a coronary pressure wire at the time of invasive coronary angiography identifies those with microvascular disease. This helps to correctly diagnose these patients and tailor their therapeutic strategy. A retrospective audit was undertaken of consecutive patients with NOCAD and measurement of microvascular indices from the Northern region between March 2020 and January 2023 at Auckland City Hospital. Coronary flow reserve, IMR, and fractional flow reserve were measured. Fifty-six participants were included. Seven were excluded as they resided outside the Northern region. Forty-one (75%) were male with mean age of 65 (SD 8.6) years. A total of 47% had a history of smoking, 24% previous myocardial infarction, 7% previous stroke, 51% diabetes; 52% presented with stable angina, 24% with unstable angina and 22% with non-ST elevation myocardial infarction (NSTEMI); 70% were on aspirin, 44% on beta blockers, 18% on calcium channel blockers, 31% nitrates, 38% statins, and 2% nicorandil. Normal IMR (<25) was seen in 24% of patients with an initial diagnosis of stable angina, 15% with unstable angina, and 17% with NSTEMI. Amongst those with chest pain and NOCAD, who had a microvascular assessment, four of five had an elevated IMR, suggesting significant microvascular disease. The remaining patients were reassured that their chest pain was not due to coronary disease. These data reinforce the diagnostic value of IMR in this patient cohort.

Development of artificial intelligence tools for invasive Doppler-based coronary microvascular assessment.

Coronary flow reserve (CFR) assessment has proven clinical utility, but Doppler-based methods are sensitive to noise and operator bias, limiting their clinical applicability. The objective of the study is to expand the adoption of invasive Doppler CFR, through the development of artificial intelligence (AI) algorithms to automatically quantify coronary Doppler quality and track flow velocity. A neural network was trained on images extracted from coronary Doppler flow recordings to score signal quality and derive values for coronary flow velocity and CFR. The outputs were independently validated against expert consensus. Artificial intelligence successfully quantified Doppler signal quality, with high agreement with expert consensus (Spearman's rho: 0.94), and within individual experts. Artificial intelligence automatically tracked flow velocity with superior numerical agreement against experts, when compared with the current console algorithm [AI flow vs. expert flow bias -1.68 cm/s, 95% confidence interval (CI) -2.13 to -1.23 cm/s, P < 0.001 with limits of agreement (LOA) -4.03 to 0.68 cm/s; console flow vs. expert flow bias -2.63 cm/s, 95% CI -3.74 to -1.52, P < 0.001, 95% LOA -8.45 to -3.19 cm/s]. Artificial intelligence yielded more precise CFR values [median absolute difference (MAD) against expert CFR: 4.0% for AI and 7.4% for console]. Artificial intelligence tracked lower-quality Doppler signals with lower variability (MAD against expert CFR 8.3% for AI and 16.7% for console). An AI-based system, trained by experts and independently validated, could assign a quality score to Doppler traces and derive coronary flow velocity and CFR. By making Doppler CFR more automated, precise, and operator-independent, AI could expand the clinical applicability of coronary microvascular assessment.

Comparison of the EndoPAT device with a unique vascular assessment of reactive hyperemia

The EndoPAT device (Itamar Medical) is used to determine endothelial function by using peripheral arterial tonometry during reactive hyperemia. It has been shown to be related to the gold standard non-invasive technique of flow-mediated dilation ultrasound assessment. These methodologies have technical requirements and/or ongoing operational costs that could be prohibitive to under-resourced clinics or researchers. We hypothesized that using a re-usable and cost-effective procedure of determining the reactive hyperemic response using piezo-electric pulse transducers (ADInstruments) would give similar results to the EndoPAT. Reactive hyperemia was induced by occluding blood flow to the forearm for 5 minutes using a blood pressure cuff inflated to +50mmHg above systolic blood pressure. The vascular response to the release of the occlusion was assessed using EndoPAT on the index fingers and using piezo-electric transducers on the middle fingers, concurrently. Twenty-five healthy participants (15 female; 31±12years) participated in the study. Participants refrained from caffeine, alcohol, fatty foods, smoking and strenuous exercise for at least 12 hours prior to testing. The EndoPAT reactive hyperemia index (RHI) was determined using proprietary software. The area under the curve (AUC) of the finger pulse waves from the piezoelectric pulse transducers was also determined. The ratio of the AUC of the peak hyperemic response (10s average) compared to the baseline period (3.5min) in the occluded arm was compared to the equivalent ratio in the control arm to determine the pulse-wave reactive hyperemia index (PWRHI). Univariate linear regression and correlation analysis was conducted between RHI and PWRHI. When comparing the two methods, Spearman’s r was 0.67 (p=0.0002) with a coefficient of determination of 0.58. We have found that the two methods correlate well to each other and the PWRHI technique has the potential to make microvascular assessments more accessible to clinicians and researchers. Our PWRHI method still needs to be validated in larger populations with vascular dysfunction and over a wider age-range. Funding provided by the Natural Sciences and Engineering Research Council of Canada. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Ultrasound localization microscopy of the human kidney allograft on a clinical ultrasound scanner

Chronic kidney disease is a major medical problem, causing more than a million deaths each year worldwide. Peripheral kidney microvascular damage characterizes most chronic kidney diseases, yet noninvasive and quantitative diagnostic tools to measure this are lacking. Ultrasound Localization Microscopy (ULM) can assess tissue microvasculature with unprecedented resolution. Here, we optimized methods on 35 kidney transplants and studied the feasibility of ULM in seven human kidney allografts with a standard low frame rate ultrasound scanner to access microvascular damage. Interlobar, arcuate, cortical radial vessels, and part of the medullary organization were visible on ULM density maps. The medullary vasa recta can be seen but are not as clear as the cortical vessels. Acquisition parameters were derived from Contrast-Enhanced Ultrasound examinations by increasing the duration of the recorded clip at the same plane. ULM images were compared with Color Doppler, Advanced Dynamic Flow, and Superb Microvascular Imaging with a contrast agent. Despite some additional limitations due to movement and saturation artifacts, ULM identified vessels two to four times thinner compared with Doppler modes. The mean ULM smallest analyzable vessel cross section was 0.3 ± 0.2 mm in the seven patients. Additionally, ULM was able to provide quantitative information on blood velocities in the cortical area. Thus, this proof-of-concept study has shown ULM to be a promising imaging technique for qualitative and quantitative microvascular assessment. Imaging native kidneys in patients with kidney diseases will be needed to identify their ULM biomarkers.

MetfOrmin BenefIts Lower Extremities with Intermittent Claudication (MOBILE IC): randomized clinical trial protocol

BackgroundPeripheral artery disease (PAD) affects over 230 million people worldwide and is due to systemic atherosclerosis with etiology linked to chronic inflammation, hypertension, and smoking status. PAD is associated with walking impairment and mobility loss as well as a high prevalence of coronary and cerebrovascular disease. Intermittent claudication (IC) is the classic presenting symptom for PAD, although many patients are asymptomatic or have atypical presentations. Few effective medical therapies are available, while surgical and exercise therapies lack durability. Metformin, the most frequently prescribed oral medication for Type 2 diabetes, has salient anti-inflammatory and promitochondrial properties. We hypothesize that metformin will improve function, retard the progression of PAD, and improve systemic inflammation and mitochondrial function in non-diabetic patients with IC.Methods200 non-diabetic Veterans with IC will be randomized 1:1 to 180-day treatment with metformin extended release (1000 mg/day) or placebo to evaluate the effect of metformin on functional status, PAD progression, cardiovascular disease events, and systemic inflammation. The primary outcome is 180-day maximum walking distance on the 6-min walk test (6MWT). Secondary outcomes include additional assessments of functional status (cardiopulmonary exercise testing, grip strength, Walking Impairment Questionnaires), health related quality of life (SF-36, VascuQoL), macro- and micro-vascular assessment of lower extremity blood flow (ankle brachial indices, pulse volume recording, EndoPAT), cardiovascular events (amputations, interventions, major adverse cardiac events, all-cause mortality), and measures of systemic inflammation. All outcomes will be assessed at baseline, 90 and 180 days of study drug exposure, and 180 days following cessation of study drug. We will evaluate the primary outcome with linear mixed-effects model analysis with covariate adjustment for baseline 6MWT, age, baseline ankle brachial indices, and smoking status following an intention to treat protocol.DiscussionMOBILE IC is uniquely suited to evaluate the use of metformin to improve both systematic inflammatory responses, cellular energetics, and functional outcomes in patients with PAD and IC.Trial Registration: The prospective MOBILE IC trial was publicly registered (NCT05132439) November 24, 2021.

Pilot study of optical coherence tomography angiography-derived microvascular metrics in hands and feet of healthy and diabetic people

Optical coherence tomography angiography (OCTA) is a non-invasive, high-resolution imaging modality with growing application in dermatology and microvascular assessment. Accepted reference values for OCTA-derived microvascular parameters in skin do not yet exist but need to be established to drive OCTA into the clinic. In this pilot study, we assess a range of OCTA microvascular metrics at rest and after post-occlusive reactive hyperaemia (PORH) in the hands and feet of 52 healthy people and 11 people with well-controlled type 2 diabetes mellitus (T2DM). We calculate each metric, measure test–retest repeatability, and evaluate correlation with demographic risk factors. Our study delivers extremity-specific, age-dependent reference values and coefficients of repeatability of nine microvascular metrics at baseline and at the maximum of PORH. Significant differences are not seen for age-dependent microvascular metrics in hand, but they are present for several metrics in the foot. Significant differences are observed between hand and foot, both at baseline and maximum PORH, for most of the microvascular metrics with generally higher values in the hand. Despite a large variability over a range of individuals, as is expected based on heterogeneous ageing phenotypes of the population, the test–retest repeatability is 3.5% to 18% of the mean value for all metrics, which highlights the opportunities for OCTA-based studies in larger cohorts, for longitudinal monitoring, and for assessing the efficacy of interventions. Additionally, branchpoint density in the hand and foot and changes in vessel diameter in response to PORH stood out as good discriminators between healthy and T2DM groups, which indicates their potential value as biomarkers. This study, building on our previous work, represents a further step towards standardised OCTA in clinical practice and research.

Evaluation of Microvascular Rarefaction in Vascular Cognitive Impairment and Heart Failure (CRUCIAL): Study Protocol for an Observational Study

Introduction: Microvascular rarefaction, the functional reduction in perfused microvessels and structural reduction of microvascular density, seems to be an important mechanism in the pathophysiology of small blood vessel-related disorders including vascular cognitive impairment (VCI) due to cerebral small vessel disease and heart failure with preserved ejection fraction (HFpEF). Both diseases share common risk factors including hypertension, diabetes mellitus, obesity, and ageing; in turn, these comorbidities are associated with microvascular rarefaction. Our consortium aims to investigate novel non-invasive tools to quantify microvascular health and rarefaction in both organs, as well as surrogate biomarkers for cerebral and/or cardiac rarefaction (via sublingual capillary health, vascular density of the retina, and RNA content of circulating extracellular vesicles), and to determine whether microvascular density relates to disease severity. Methods: The clinical research program of CRUCIAL consists of four observational cohort studies. We aim to recruit 75 VCI patients, 60 HFpEF patients, 60 patients with severe aortic stenosis (AS) undergoing surgical aortic valve replacement as a pressure overload HFpEF model, and 200 elderly participants with mixed comorbidities to serve as controls. Data collected will include medical history, physical examination, cognitive testing, advanced brain and cardiac MRI, ECG, echocardiography, sublingual capillary health, optical coherence tomography angiography (OCTa), extracellular vesicles RNA analysis, and myocardial remodelling-related serum biomarkers. The AS cohort undergoing surgery will also have myocardial biopsy for histological microvascular assessment. Discussion: CRUCIAL will examine the pathophysiological role of microvascular rarefaction in VCI and HFpEF using advanced brain and cardiac MRI techniques. Furthermore, we will investigate surrogate biomarkers for non-invasive, faster, easier, and cheaper assessment of microvascular density since these are more likely to be disseminated into widespread clinical practice. If microvascular rarefaction is an early marker of developing small vessel diseases, then measuring rarefaction may allow preclinical diagnosis, with implications for screening, risk stratification, and prevention. Further knowledge of the relevance of microvascular rarefaction and its underlying mechanisms may provide new avenues for research and therapeutic targets.