Clinical Validation of Carotid-Femoral Pulse Wave Velocity Measurement Using a Multi-Beam Laser Vibrometer: The CARDIS Study.

BACKGROUND: Carotid-femoral pulse wave velocity (cfPWV) is the gold standard for noninvasive arterial stiffness assessment, an independent predictor of cardiovascular disease, and a potential parameter to guide therapy. However, cfPWV is not routinely measured in clinical practice due to the unavailability of a low-cost, operator-friendly, and independent device. The current study validated a novel laser Doppler vibrometry (LDV)-based measurement of cfPWV against the reference technique. METHODS: In 100 (50 men) hypertensive patients, cfPWV was measured using applanation tonometry (Sphygmocor) and the novel LDV device. This device has 2 handpieces with 6 laser beams each that simultaneously measure vibrations from the skin surface at carotid and femoral sites. Pulse wave velocity is calculated using ECG for the identification of cardiac cycles. An ECG-independent method was also devised. Cardiovascular risk score was calculated for patients between 40 and 75 years old using the WHO risk scoring chart. RESULTS: LDV-based cfPWV correlated significantly with tonometry (r=0.86, P<0.0001 ECG-dependent [cfPWVLDV_ECG] and r=0.80, P<0.001 ECG-independent [cfPWVLDV_w/oECG] methods). Bland-Altman analysis showed nonsignificant bias (0.65 m/s) and acceptable SD (1.27 m/s) between methods. Intraobserver coefficient of variance for LDV was 4.7% (95% CI, 3.0%-5.5%), and interobserver coefficient of variance was 5.87%. CfPWV correlated significantly with CVD risk (r=0.64, P<0.001; r=0.41, P=0.003; and r=0.37, P=0.006 for tonometry, LDV-with, and LDV-without ECG, respectively). CONCLUSIONS: The study demonstrates clinical validity of the LDV device. The LDV provides a simple, noninvasive, operator-independent method to measure cfPWV for assessing arterial stiffness, comparable to the standard existing techniques. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03446430.

Silicon photonics-based laser Doppler vibrometer array for carotid-femoral pulse wave velocity (PWV) measurement.

Pulse wave velocity (PWV) is a reference measure for aortic stiffness, itself an important biomarker of cardiovascular risk. To enable low-cost and easy-to-use PWV measurement devices that can be used in routine clinical practice, we have designed several handheld PWV sensors using miniaturized laser Doppler vibrometer (LDV) arrays in a silicon photonics platform. The LDV-based PWV sensor design and the signal processing protocol to obtain pulse transit time (PTT) and carotid-femoral PWV in a feasibility study in humans, are described in this paper. Compared with a commercial reference PWV measurement system, measuring arterial pressure waveforms by applanation tonometry, LDV-based displacement signals resulted in more complex signals. However, we have shown that it is possible to identify reliable fiducial points for PTT calculation using the maximum of the 2nd derivative algorithm in LDV-based signals, comparable to those obtained by the reference technique, applanation tonometry.

Quality-based pharmacokinetic model selection on DCE-MRI for characterizing orbital lesions.

BACKGROUND: Although several studies have evaluated dynamic contrast-enhanced (DCE) MRI in the orbit, showing its utility when detecting and diagnosing orbital lesions, none have evaluated the pharmacokinetic models. PURPOSE: To provide a quality-based pharmacokinetic model selection for characterizing orbital lesions using DCE-MRI at 3.0T. STUDY TYPE: Prospective. POPULATION: From December 2015 to April 2017, 151 patients with an orbital lesion underwent MRI prior to surgery, including a high temporal resolution DCE sequence, divided into one training and one test dataset with 100 and 51 patients, respectively. FIELD STRENGTH/SEQUENCE: 3T/DCE. ASSESSMENT: Six different pharmacokinetic models were tested. STATISTICAL TESTS: Univariate and multivariate analyses were performed using Wilcoxon-2-sample tests and a logistic regression to compare parameters between malignant and benign tumors for each pharmacokinetic model for the whole cohort. Receiver operating characteristic (ROC) curve analyses were performed on the training dataset to determine area under curve (AUC) and optimal cutoff values for each pharmacokinetic model, then validated on the test dataset to calculate sensitivity, specificity, and accuracy. RESULTS: Regardless of the model, tissue blood flow and tissue blood volume values were significantly higher in malignant vs. benign lesions: 103.8-195.1 vs. 65-113.8, P [<10-4 -2.10-4 ] and 21.3-36.9 vs. 15.6-33.6, P [<10-4 -0.03] respectively. Extracellular volume fraction and permeability-surface area product or transfer constant appeared to be less relevant: 17.3-27.5 vs. 22.8-28.2, P [0.01-0.7], 1.7-4.9, P [0.2-0.9] and 9.5-38.8 vs. 8.1-22.8, P [<10-4 -0.6], respectively. ROC curves showed no significant differences in AUC between the different models. The two-compartment exchange (2CX) model ranked first for quality. DATA CONCLUSION: DCE MRI pharmacokinetic model-derived parameters appeared to be useful for discriminating benign from malignant orbital lesions. The 2CX model provided the best quality of modeling and should be recommended. Perfusion-related DCE parameters appeared to be significantly more relevant to the diagnostic process. Level of Evidence 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;50:1514-1525.

Deep Vascular Phenotyping in Patients With Renal Multifocal Fibromuscular Dysplasia.

Arterial fibromuscular dysplasia is a nonatherosclerotic, noninflammatory vascular disease, whose pathophysiology is still unknown. We performed deep image-based vascular phenotyping of nonaffected arteries to look for systemic vascular alterations in fibromuscular dysplasia. This single center cross-sectional study included 50 patients with multifocal renal fibromuscular dysplasia, 50 hypertensive patients, and 50 healthy controls, matched for age, sex, and ethnicity; hypertensive patients were matched also for blood pressure. Brachial artery endothelium-dependent and endothelium-independent dilation were studied by echotracking. Aortic stiffness was assessed by carotid-to-femoral pulse wave velocity. We quantified the presence of supernumerary acoustic interfaces within the common carotid wall by the triple signal (TS) score. We plotted the Young incremental elastic modulus/stress curves for common carotid artery, derived from echotracking and tonometry. Patients with fibromuscular dysplasia had impaired endothelium-independent dilation (adjusted P=0.002), smaller brachial artery diameter but comparable endothelium-dependent dilation and aortic stiffness. The prevalence of TS score >6 was 56%, 40%, 24% in patients with fibromuscular dysplasia, hypertensives, and controls, respectively ( P=0.005). Fibromuscular dysplasia remained significantly associated with TS in the multiple regression model ( P=0.022). Impaired endothelium-dependent dilation was present only in patients with fibromuscular dysplasia, TS score >6 ( P=0.047). Incremental elastic modulus was higher for a given wall stress (80 kPa) in the presence of a TS score >6, especially in fibromuscular dysplasia. In conclusion, nonclinically affected large- and medium-sized arteries in patients with multifocal renal fibromuscular dysplasia exhibit a cluster of diffuse alterations in smooth muscle cell function, arterial geometry, wall characteristics, and mechanical properties. Clinical Trial Registration URL: http://www.clinicaltrials.gov . Unique identifier: NCT01935752.

Arterial Stiffness Assessment by Shear Wave Elastography and Ultrafast Pulse Wave Imaging: Comparison with Reference Techniques in Normotensives and Hypertensives.

Shear wave elastography and ultrafast imaging of the carotid artery pulse wave were performed in 27 normotensive participants and 29 age- and sex-matched patients with essential hypertension, and compared with reference techniques: carotid-femoral pulse wave velocity (cfPWV) determined via arterial tonometry and carotid stiffness (carPWV) determined via echotracking. Shear wave speed in the carotid anterior (a-SWS) and posterior (p-SWS) walls were assessed throughout the cardiac cycle. Ultrafast PWV was measured in early systole (ufPWV-FW) and in end-systole (dicrotic notch, ufPWV-DN). Shear wave speed in the carotid anterior appeared to be the best candidate to evaluate arterial stiffness from ultrafast imaging. In univariate analysis, a-SWS was associated with carPWV (r = 0.56, p = 0.003) and carotid-to-femoral PWV (r = 0.66, p < 0.001). In multivariate analysis, a-SWS was independently associated with age (R²â€¯= 0.14, p = 0.02) and blood pressure (R²â€¯= 0.21, p = 0.004). Moreover, a-SWS increased with blood pressure throughout the cardiac cycle and did not differ between normotensive participants and patients with essential hypertension when compared at similar blood pressures.

Mechanical behavior of the abdominal aortic aneurysm assessed by biaxial tests in the rat xenograft model.

This paper addresses the mechanical biaxial behavior of degraded arteries obtained by the rat xenograft model. For that, a pressure myograph was used to perform extension-inflation tests on abdominal aortic aneurysms (AAAs). Furthermore, residual stresses in the aneurismal wall were assessed by opening angle tests. Thus, the changes in mechanical behavior between native murine aortas, decellularized guinea pig aortas (the grafts) and degraded aortas (AAAs) were investigated. It was shown that decellularized and degraded aortas exhibited a different mechanical behavior than native murine aortas. Indeed, decellularized aortas presented a marked decrease in circumferential stretch and distensibility compared with native aortas. Moreover, we evidenced an exacerbation of these changes in mechanical behavior for AAAs, which showed the lowest distension and distensibility at 100mmHg. The opening angle test also revealed a complete loss of residual stresses in the degraded arterial wall given the non opening of rings extracted from AAAs.

Evaluation of arterial stiffness by finger-toe pulse wave velocity: optimization of signal processing and clinical validation.

BACKGROUND: Carotid-femoral pulse wave velocity (PWV) (cf-PWV) is the gold standard for measuring aortic stiffness. Finger-toe PWV (ft-PWV) is a simpler noninvasive method for measuring arterial stiffness. Although the validity of the method has been previously assessed, its accuracy can be improved. ft-PWV is determined on the basis of a patented height chart for the distance and the pulse transit time (PTT) between the finger and the toe pulpar arteries signals (ft-PTT). METHOD: The objective of the first study, performed in 66 patients, was to compare different algorithms (intersecting tangents, maximum of the second derivative, 10% threshold and cross-correlation) for determining the foot of the arterial pulse wave, thus the ft-PTT. The objective of the second study, performed in 101 patients, was to investigate different signal processing chains to improve the concordance of ft-PWV with the gold-standard cf-PWV. Finger-toe PWV (ft-PWV) was calculated using the four algorithms. RESULTS: The best correlations relating ft-PWV and cf-PWV, and relating ft-PTT and carotid-femoral PTT were obtained with the maximum of the second derivative algorithm [PWV: r = 0.56, P < 0.0001, root mean square error (RMSE) = 0.9 m/s; PTT: r = 0.61, P < 0.001, RMSE = 12 ms]. The three other algorithms showed lower correlations. The correlation between ft-PTT and carotid-femoral PTT further improved (r = 0.81, P < 0.0001, RMSE = 5.4 ms) when the maximum of the second derivative algorithm was combined with an optimized signal processing chain. CONCLUSION: Selecting the maximum of the second derivative algorithm for detecting the foot of the pressure waveform, and combining it with an optimized signal processing chain, improved the accuracy of ft-PWV measurement in the current population sample. Thus, it makes ft-PWV very promising for the simple noninvasive determination of aortic stiffness in clinical practice.

Diameter and thickness-related variations in mechanical properties of degraded arterial wall in the rat xenograft model.

The purpose of this study was to evaluate the diameter and thickness-related variations in mechanical properties of degraded arterial wall. To this end, ring tests were performed on 31 samples from the rat xenograft model of abdominal aortic aneurysm (AAA) and failure properties were determined. An inverse finite element method was then employed to identify the material parameters of a hyperelastic and incompressible strain energy function. Correlations with outer diameter and wall thickness of the rings were examined. Furthermore, we investigated the changes in mechanical properties between the grafts, which consist in guinea pig decellularized aortas, native murine aortas and degraded aortas (AAAs). Decellularized aortas presented a significantly lower ultimate strain associated with a higher stiffening rate compared to native aortas. AAAs exhibited a significantly lower ultimate stress than other groups and an extensible-but-stiff behavior. The proposed approach revealed correlations of ultimate stress and material parameters of aneurysmal aortas with outer diameter and thickness. In particular, the negative correlations of the material parameter accounting for the response of the non-collagenous matrix with diameter and thickness (r=-0.67 and r=-0.73, p<0.001) captured the gradual loss of elastin with dilatation observed in histology (r=-0.97, p<0.001). Moreover, it exposed the progressive weakening of the wall with enlargement and thickening (r=-0.64 and r=-0.69, p<0.001), suggesting that wall thickness and diameter may be indicators of rupture risk in the rat xenograft model.

The Noninvasive Assessment of Vascular Aging.

The growing interest in the clinical measurement of arterial aging through the noninvasive assessment of arterial stiffness is associated with important developments in novel methods and apparatus. In this review, we aimed to describe the major principles of the measurement of arterial stiffness and to critically review the advantages and limitations of the different methods. The measurement of regional stiffness is recommended by international guidelines for routine clinical practice. It is most often determined through pulse wave velocity (PWV) between 2 arterial sites. Methods using a single-site cuff-based measurement are promising. Local determination of arterial stiffness, obtained either with the well-established, high-resolution echo tracking systems or more recently with magnetic resonance imaging, is indicated for pathophysiological and pharmacologic studies. Novel apparatus that were developed for determining arterial stiffness claimed superiority over pioneering methods either through greater simplicity of use, better repeatability, or a more pertinent arterial pathway. However, the true additive value of measuring arterial aging with a given apparatus had to be translated into the predictive value of arterial stiffness as an intermediate end point, ie, the higher the arterial stiffness the higher the number of cardiovascular (CV) events. Thus, another important aim of this review was to analyze the amount of epidemiologic evidence obtained with a given method regarding the predictive value of arterial stiffness for CV events.