3D Visualisation of Navigation Catheters for Endovascular Procedures Using a 3D Hub and Fiber Optic RealShape Technology: Phantom Study Results.

Objective: Fiber Optic RealShape (FORS) is a new technology that visualises the full three dimensional (3D) shape of guidewires using an optical fibre embedded in the device. Co-registering FORS guidewires with anatomical images, such as a digital subtraction angiography (DSA), provides anatomical context for navigating these devices during endovascular procedures. The objective of this study was to demonstrate the feasibility and usability of visualising compatible conventional navigation catheters, together with the FORS guidewire, in phantom with a new 3D Hub technology and to understand potential clinical benefits. Methods: The accuracy of localising the 3D Hub and catheter in relation to the FORS guidewire, was evaluated using a translation stage test setup and a retrospective analysis of prior clinical data. Catheter visualisation accuracy and navigation success was assessed in a phantom study where 15 interventionists navigated devices to three pre-defined targets in an abdominal aortic phantom using an Xray or computed tomography angiography (CTA) roadmap. Additionally, the interventionists were surveyed about the usability and potential benefits of the 3D Hub. Results: The location of the 3D Hub and catheter along the FORS guidewire was detected correctly 96.59% of the time. During the phantom study, all 15 interventionists successfully reached the target locations 100% of the time and the error in catheter visualisation was 0.69 mm. The interventionists agreed or strongly agreed that the 3D Hub was easy to use and the greatest potential clinical benefit over FORS is in offering interventionists choice over which catheter they used. Conclusion: This set of studies has shown that FORS guided catheter visualisation, enabled by a 3D Hub, is accurate and easy to use in a phantom setting. Further evaluation is needed to understand the benefits and limitations of the 3D Hub technology during endovascular procedures.

Inter-Relations of Orthostatic Blood Pressure Change, Aortic Stiffness, and Brain Structure and Function in Young Adults.

BACKGROUND: Relations of orthostatic change in blood pressure with brain structure and function have not been studied thoroughly, particularly in younger, healthier individuals. Elucidation of factors that contribute to early changes in brain integrity may lead to development of interventions that delay or prevent cognitive impairment. METHODS AND RESULTS: In a sample of the Framingham Heart Study Third Generation (N=2119; 53% women; mean age±SD, 47±8 years), we assessed orthostatic change in mean arterial pressure (MAP), aortic stiffness (carotid-femoral pulse wave velocity), neuropsychological function, and markers of subclinical brain injury on magnetic resonance imaging. Multivariable regression analyses were used to assess relations between orthostatic change in MAP and brain structural and neuropsychological outcomes. Greater orthostatic increase in MAP on standing was related to better Trails B-A performance among participants aged <49 years (ß±SE, 0.062±0.029; P=0.031) and among participants with carotid-femoral pulse wave velocity <6.9 m/s (ß±SE, 0.063±0.026; P=0.016). This relation was not significant among participants who were older or had stiffer aortas. Conversely, greater orthostatic increase in MAP was related to larger total brain volume among older participants (ß±SE, 0.065±0.029; P=0.023) and among participants with carotid-femoral pulse wave velocity ≥6.9 m/s (ß±SE, 0.078±0.031; P=0.011). CONCLUSIONS: Blunted orthostatic increase in MAP was associated with smaller brain volume among participants who were older or had stiffer aortas and with poorer executive function among persons who were younger or who had more-elastic aortas. Our findings suggest that the brain is sensitive to orthostatic change in MAP, with results dependent on age and aortic stiffness.

Ultrafast wavelength multiplexed broad bandwidth digital diffuse optical spectroscopy for in vivo extraction of tissue optical properties.

Frequency-domain diffuse optical spectroscopy (FD-DOS) utilizes intensity-modulated light to characterize optical scattering and absorption in thick tissue. Previous FD-DOS systems have been limited by large device footprints, complex electronics, high costs, and limited acquisition speeds, all of which complicate access to patients in the clinical setting. We have developed a new digital DOS (dDOS) system, which is relatively compact and inexpensive, allowing for simplified clinical use, while providing unprecedented measurement speeds. The dDOS system utilizes hardware-integrated custom board-level direct digital synthesizers and an analog-to-digital converter to generate frequency sweeps and directly measure signals utilizing undersampling at six wavelengths modulated at discrete frequencies from 50 to 400 MHz. Wavelength multiplexing is utilized to achieve broadband frequency sweep measurements acquired at over 97 Hz. When compared to a gold-standard DOS system, the accuracy of optical properties recovered with the dDOS system was within 5.3% and 5.5% for absorption and reduced scattering coefficient extractions, respectively. When tested in vivo, the dDOS system was able to detect physiological changes throughout the cardiac cycle. The new FD-dDOS system is fast, inexpensive, and compact without compromising measurement quality.

Relations of Arterial Stiffness With Postural Change in Mean Arterial Pressure in Middle-Aged Adults: The Framingham Heart Study.

Impaired regulation of blood pressure on standing can lead to adverse outcomes, including falls, syncope, and disorientation. Mean arterial pressure (MAP) typically increases on standing; however, an insufficient increase or a decline in MAP on standing may result in decreased cerebral perfusion. Orthostatic hypotension has been reported in older people with increased arterial stiffness, whereas the association between orthostatic change in MAP and arterial stiffness in young- to middle-aged individuals has not been examined. We analyzed orthostatic blood pressure response and comprehensive hemodynamic data in 3205 participants (1693 [53%] women) in the Framingham Heart Study Third Generation cohort. Participants were predominantly middle aged (mean age: 46±9 years). Arterial stiffness was assessed using carotid-femoral pulse wave velocity, forward pressure wave amplitude, and characteristic impedance of the aorta. Adjusting for standard cardiovascular disease risk factors, orthostatic change in MAP (6.9±7.7 mm Hg) was inversely associated with carotid-femoral pulse wave velocity (partial correlation, rp=-0.084; P<0.0001), forward wave amplitude (rp=-0.129; P<0.0001), and characteristic impedance (rp=-0.094; P<0.0001). The negative relation between forward wave amplitude and change in MAP on standing was accentuated in women (P=0.002 for sex interaction). Thus, higher aortic stiffness was associated with a blunted orthostatic increase in MAP, even in middle age. The clinical implications of these findings warrant further study.

Cerebrovascular Damage Mediates Relations Between Aortic Stiffness and Memory.

Aortic stiffness is associated with cognitive decline. Here, we examined the association between carotid-femoral pulse wave velocity and cognitive function and investigated whether cerebrovascular remodeling and parenchymal small vessel disease damage mediate the relation. Analyses were based on 1820 (60% women) participants in the Age, Gene/Environment Susceptibility-Reykjavik Study. Multivariable linear regression models adjusted for vascular and demographic confounders showed that higher carotid-femoral pulse wave velocity was related to lower memory score (standardized ß: -0.071±0.023; P=0.002). Cerebrovascular resistance and white matter hyperintensities were each associated with carotid-femoral pulse wave velocity and memory (P<0.05). Together, cerebrovascular resistance and white matter hyperintensities (total indirect effect: -0.029; 95% CI, -0.043 to -0.017) attenuated the direct relation between carotid-femoral pulse wave velocity and memory (direct effect: -0.042; 95% CI, -0.087 to 0.003; P=0.07) and explained ≈41% of the observed effect. Our results suggest that in older adults, associations between aortic stiffness and memory are mediated by pathways that include cerebral microvascular remodeling and microvascular parenchymal damage.

Relations between aortic stiffness and left ventricular structure and function in older participants in the Age, Gene/Environment Susceptibility--Reykjavik Study.

BACKGROUND: Left ventricular (LV) contraction displaces the aortic annulus and produces a force that stretches the ascending aorta. We hypothesized that aortic stiffening increases this previously ignored component of LV load and may contribute to hypertrophy. Conversely, aortic stretch-related work represents stored energy that may facilitate early diastolic filling. METHODS AND RESULTS: We performed MRI of the aorta and LV in 347 participants (72-91 years old, 189 women) in the Age, Gene/Environment Susceptibility-Reykjavik Study to examine relations of aortic stretch with LV structure and function. Aortic stiffness was evaluated as the product of Young's modulus and aortic wall thickness. Force was computed from Young's modulus and longitudinal aortic strain; work was the integrated product of force and annulus displacement during systole. LV mass and dynamic volume were measured using the area-length method. Filling was assessed from time-resolved LV volume curves. In multivariable models that adjusted for age, sex, height, weight, end-diastolic LV volume, augmentation index, end-systolic pressure, and cardiovascular disease risk factors, higher aortic stiffness was associated with increased LV mass (ß=3.0±0.8% per SD, P<0.001; sex interaction, P=0.8). Greater stretch-related aortic work was associated with enhanced early filling in men (ß=4.0±0.8 mL/SD; P<0.001), but not in women (ß=-0.4±0.7 mL/SD; P=0.6). CONCLUSIONS: Higher aortic stiffness was associated with higher LV mass, independently of pressure. Higher stretch-related work was associated with greater early diastolic filling in men only. Impaired diastolic recovery of energy stored by systolic proximal aortic stretch may contribute to increased susceptibility to diastolic dysfunction in women.

Mediation analysis of aortic stiffness and renal microvascular function.

Aortic stiffening, assessed by carotid-femoral pulse wave velocity, is associated with CKD. Transmission of excessive flow pulsatility into the low-impedance renal microvasculature may mediate this association. However, direct analyses of macrovascular-microvascular relations in the kidney are limited. Using arterial tonometry, iohexol clearance, and magnetic resonance imaging, we related arterial stiffness, GFR, urinary albumin excretion, and potential mediators, including renal artery pulsatility index, renal vascular resistance, and arterial volume in the cortex, in 367 older adults (ages 72-92 years) participating in the Age, Gene/Environment Susceptibility-Reykjavik Study. In a model adjusted for age, sex, heart rate, and body size, aortic stiffness was related to GFR (Slope of regression B=-2.28±0.85 ml/min per SD, P=0.008) but not urine albumin (P=0.09). After accounting for pulsatility index, the relation between aortic stiffness and GFR was no longer significant (P=0.10). Mediation analysis showed that 34% of the relation between aortic stiffness and GFR was mediated by pulsatility index (95% confidence interval of indirect effect, -1.35 to -0.29). An additional 20% or 36% of the relation was mediated by lower arterial volume in the cortex or higher renal vascular resistance, respectively, when offered as mediators downstream from higher pulsatility index (95% confidence interval of indirect effect including arterial volume in the cortex, -2.22 to -0.40; 95% confidence interval of indirect effect including renal vascular resistance, -2.51 to -0.76). These analyses provide the first evidence that aortic stiffness may contribute to lower GFR by transferring excessive flow pulsatility into the susceptible renal microvasculature, leading to dynamic constriction or vessel loss.

Segmental kidney volumes measured by dynamic contrast-enhanced magnetic resonance imaging and their association with CKD in older people.

BACKGROUND: Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is a potentially powerful tool for analysis of kidney structure and function. The ability to measure functional and hypofunctional tissues could provide important information in groups at risk for chronic kidney disease (CKD), such as the elderly. STUDY DESIGN: Observational study with a cross-sectional design. SETTING & PARTICIPANTS: 493 volunteers (aged 72-94 years; 278 women; mean estimated glomerular filtration rate [eGFR], 67±15mL/min/1.73m(2); 40% with CKD) in the Age, Gene/Environment Susceptibility (AGES)-Reykjavik Study. PREDICTOR: DCE-MRI kidney segmentation data. OUTCOMES & MEASUREMENTS: eGFR, urine albumin-creatinine ratio (ACR), and risk factors for and complications of CKD. RESULTS: After adjustment for age, sex, and height, eGFR was related to kidney volume (ΔR²=0.19; P<0.001), cortex volume (ΔR²=0.14; P<0.001), medulla volume (ΔR²=0.18; P<0.001), and volume percentages of fibrosis (ΔR²=0.03; P<0.001) and fat (ΔR²=0.01; P=0.03). In similarly adjusted models, log(ACR) was related to kidney volume (ΔR²=0.02; P<0.001) and fibrosis volume percentage (ΔR²=0.03; P<0.001). Using multivariable regression models adjusted for eGFR, ACR, age, sex, and height, kidney volume was related positively to body mass index (B=29.9±2.1[SE]mL; P<0.001), smoking (B=19.7±7.7mL; P=0.01), and diabetes mellitus (B=14.8±7.1mL; P=0.04) and negatively to hematocrit (B=-4.4±2.1mL; P=0.04 [model R²=0.72; P<0.001]); relations were per 1-SD greater value of the variable. Fibrosis volume percentage was associated positively with body mass index (B=0.28±0.03; P<0.001), cardiac output (B=0.15±0.03; P<0.001), and heart rate (B=0.08±0.03; P=0.01) and negatively with hematocrit (B=-0.07±0.3; P=0.02) and augmentation index (B=-0.06±0.03; P=0.04 [model R²=0.49; P<0.001]); again, relations are per 1-SD greater value of the variable. LIMITATIONS: Automatic segmentations were not validated by histology. The limited age range prevented meaningful interpretation of age effects on measured data or the automatic segmentation procedure. CONCLUSIONS: Kidney volume, cortex volume, and hypofunctional volume fraction assessed by DCE-MRI may provide information about CKD risk and prognosis beyond that provided by eGFR and urine ACR.

Longitudinal and circumferential strain of the proximal aorta.

BACKGROUND: Accurate assessment of mechanical properties of the proximal aorta is a requisite first step for elucidating the pathophysiology of isolated systolic hypertension. During systole, substantial proximal aortic axial displacement produces longitudinal strain, which we hypothesize causes variable underestimation of ascending aortic circumferential strain compared to values in the longitudinally constrained descending aorta. METHODS AND RESULTS: To assess effects of longitudinal strain, we performed magnetic resonance imaging in 375 participants (72 to 94 years old, 204 women) in the Age, Gene/Environment Susceptibility­Reykjavik Study and measured aortic circumferential and longitudinal strain. Circumferential ascending aortic area strain uncorrected for longitudinal strain was comparable in women and men (mean [95% CI], 8.3 [7.8, 8.9] versus 7.9 [7.4, 8.5]%, respectively, P=0.3). However, longitudinal strain was greater in women (8.5±2.5 versus 7.0±2.5%, P<0.001), resulting in greater longitudinally corrected circumferential ascending aortic strain (14.4 [13.6, 15.2] versus 13.0 [12.4, 13.7]%, P=0.010). Observed circumferential descending aortic strain, which did not require correction (women: 14.0 [13.2, 14.8], men: 12.4 [11.6, 13.2]%, P=0.005), was larger than uncorrected (P<0.001), but comparable to longitudinally corrected (P=0.12) circumferential ascending aortic strain. Carotid­femoral pulse wave velocity did not correlate with uncorrected ascending aortic strain (R=−0.04, P=0.5), but was inversely related to longitudinally corrected ascending and observed descending aortic strain (R=−0.15, P=0.004; R=−0.36, P<0.001, respectively). Longitudinal strain was also inversely related to carotid­femoral pulse wave velocity and other risk factors for higher aortic stiffness including treated hypertension. CONCLUSIONS: Longitudinal strain creates substantial and variable errors in circumferential ascending aortic area strain measurements, particularly in women, and should be considered to avoid misclassification of ascending aortic stiffness.

Pulse pressure relation to aortic and left ventricular structure in the Age, Gene/Environment Susceptibility (AGES)-Reykjavik Study.

High pulse pressure, a major cardiovascular risk factor, has been attributed to medial elastic fiber degeneration and aortic dilation, which transfers hemodynamic load to stiffer collagen. However, recent studies suggest higher pulse pressure is instead associated with smaller aortic diameter. Thus, we sought to elucidate relations of pulse pressure with aortic stiffness and aortic and cardiac dimensions. We used magnetic resonance imaging to examine relationships of pulse pressure with lumen area and wall stiffness and thickness in the thoracic aorta and left ventricular structure in 526 participants (72-94 years of age, 295 women) in the community-based Age, Gene/Environment Susceptibility-Reykjavik Study. In a multivariable model that adjusted for age, sex, height, weight, and standard vascular risk factors, central pulse pressure had a negative relationship with aortic lumen area (all effects expressed as mm Hg/SD; B=-8.1±1.2; P<0.001) and positive relationships with left ventricular end-diastolic volume (B=3.8±1.0; P<0.001), carotid-femoral pulse wave velocity (B=3.6±1.0; P<0.001), and aortic wall area (B=3.0±1.2; P=0.015). Higher pulse pressure in older people is associated with smaller aortic lumen area and greater aortic wall stiffness and thickness and left ventricular volume. Relationships of larger ventricular volume and smaller aortic lumen with higher pulse pressure suggest mismatch in hemodynamic load accommodation by the heart and aorta in older people.

Forward and backward wave morphology and central pressure augmentation in men and women in the Framingham Heart Study.

Central pressure augmentation is associated with greater backward wave amplitude and shorter transit time and is higher in women for reasons only partially elucidated. Augmentation also is affected by left ventricular function and shapes of the forward and backward waves. The goal of this study was to examine the relative contributions of forward and backward wave morphology to central pressure augmentation in men and women. From noninvasive measurements of central pressure and flow in 7437 participants (4036 women) aged from 19 to 90 years (mean age, 51 years), we calculated several variables: augmentation index, backward wave arrival time, reflection factor, forward wave amplitude, forward wave peak width, and slope of the backward wave upstroke. Linear regression models for augmentation index, adjusted for height and heart rate, demonstrated nonlinear relations with age (age: B=4.6±0.1%; P<0.001; age2: B=−4.2±0.1%; P<0.001) and higher augmentation in women (B=4.5±0.4%; P<0.001; model R2=0.35). Addition of reflection factor and backward wave arrival time improved model fit (R2=0.62) and reduced the age coefficients: age (B=2.3±0.1%; P<0.001) and age2 (B=−2.2±0.1%; P<0.001). Addition of width of forward wave peak, slope of backward wave upstroke, and forward wave amplitude further improved model fit (R2=0.75) and attenuated the sex coefficient (B=1.9±0.2%; P<0.001). Thus, shape and amplitude of the forward wave may be important correlates of augmentation index, and part of the sex difference in augmentation index may be explained by forward and backward wave morphology.