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1. Harmonics of Pulsatile Pressure at Different Ages and Its Effect on Other Pulsatile Parameters and Waveform-Based Clinical Indices

   https://doi.org/10.1115/1.4062570  

   Hao, Zhili (February 2024, Journal of Engineering and Science in Medical Diagnostics and Therapy)

   Abstract Pulsatile pressure at an artery is a collection of harmonics of the heartbeat. This study examines harmonics of pulsatile pressure at different ages and its effect on other pulsatile parameters and waveform-based clinical indices. Based on a vibrating-string model of the arterial tree, wave velocity and characteristic impedance are related to arterial stiffness and radius. Blood velocity, wall shear stress (WSS), and driving force on the left ventricle (LV) are related to pulsatile pressure. Reflection magnitude and return time are related to input impedance. These relations are applied to pulsatile pressure and blood velocity at the ascending aorta (AA) and the carotid artery (CA) at different ages in a database to calculate harmonics of all the pulsatile parameters and reflection magnitude and return time at each harmonic. Harmonics of pulsatile pressure varies with aging and between the two arteries. Reflection magnitude and return time vary between harmonics. While wave reflection manifests the arterial tree (i.e., arterial stiffness and radius) and termination, harmonics of pulsatile pressure is a combination of the LV, the arterial tree, and termination. Harmonics of pulsatile pressure dictates harmonics of WSS and affects endothelial function. Harmonics of pulsatile pressure needs to serve as an independent clinical index indicative of the LV function and endothelial function. Reflection magnitude and return time of the 1st harmonic of pulsatile pressure serve as clinical indices indicative of arterial stiffness and radius. 

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2. Elastin haploinsufficiency in mice has divergent effects on arterial remodeling with aging depending on sex

   https://doi.org/10.1152/ajpheart.00517.2020  

   Hawes, Jie Z.; Cocciolone, Austin J.; Cui, Amy H.; Griffin, Diana B.; Staiculescu, Marius Catalin; Mecham, Robert P.; Wagenseil, Jessica E. (December 2020, American Journal of Physiology-Heart and Circulatory Physiology)

   null (Ed.)

   Elastin is a primary structural protein in the arterial wall that contributes to vascular mechanical properties and degrades with aging. Aging is associated with arterial stiffening and an increase in blood pressure. There is evidence that arterial aging follows different timelines with sex. Our objective was to investigate how elastin content affects arterial remodeling in male and female mice with aging. We used male and female wild-type ( Eln +/+ ) and elastin heterozygous ( Eln +/− ) mice at 6, 12, and 24 mo of age and measured their blood pressure and arterial morphology, wall structure, protein content, circumferential stress, stretch ratio, and stiffness. Two arteries were used with varying contents of elastin: the left common carotid and ascending aorta. We show that Eln +/− arteries start at a different homeostatic set point for circumferential wall stress, stretch, and material stiffness but show similar increases with aging to Eln +/+ mice. With aging, structural stiffness is greatly increased, while material stiffness and circumferential stress are only slightly increased, highlighting the importance of maintaining these homeostatic values. Circumferential stretch shows the smallest change with age and may be important for controlling cellular phenotype. Independent sex differences are mostly associated with males being larger than females; however, many of the measured factors show age × sex and/or genotype × sex interactions, indicating that males and females follow different cardiovascular remodeling timelines with aging and are differentially affected by reduced elastin content. NEW & NOTEWORTHY A comprehensive study on arterial mechanical behavior as a function of elastin content, aging, and sex in mice. Elastin haploinsufficient arteries start at a different homeostatic set point for mechanical parameters such as circumferential stress, stretch, and material stiffness. Structural stiffness of the arterial wall greatly increases with aging, as expected, but there are interactions between sex and aging for most of the mechanical parameters that are important to consider in future work. 

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3. Understanding the Role of Longitudinal Arterial Wall Motion in Blood Circulation from the Perspective of a Piano String

   Hao, Zhili (July 2020, Annual International Conference of the IEEE Engineering in Medicine and Biology Society)

   This work is aimed to establish engineering theories of the coupled longitudinal and radial motion of the arterial wall. By treating the arterial wall as a piano string in the longitudinal direction and as a viscoelastic material in the circumferential direction, and considering pulsatile pressure and wall shear stress from axial blood flow in an artery, the fully-formed governing equations of the coupled motion of the arterial wall are obtained and are related to the engineering theories of axial blood flow for a unified engineering understanding of blood circulation in the cardiovascular (CV) system. The longitudinal wall motion and the radial wall motion are essentially a longitudinal elastic wave and a transverse elastic wave, respectively, traveling along the arterial tree, with their own propagation velocities dictated by the physical properties and geometrical parameters of the arterial wall. The longitudinal initial tension is essential for generating a transverse elastic wave in the arterial wall to accompany the pulsatile pressure wave in axial blood flow. Under aging and subclinical atherosclerosis, propagation of the two elastic waves and coupling of the two elastic waves weakens and consequently might undermine blood circulation. 

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4. Computational models of ventricular mechanics and adaptation in response to right-ventricular pressure overload

   https://doi.org/10.3389/fphys.2022.948936  

   Odeigah, Oscar O.; Valdez-Jasso, Daniela; Wall, Samuel T.; Sundnes, Joakim (August 2022, Frontiers in Physiology)

   Pulmonary arterial hypertension (PAH) is associated with substantial remodeling of the right ventricle (RV), which may at first be compensatory but at a later stage becomes detrimental to RV function and patient survival. Unlike the left ventricle (LV), the RV remains understudied, and with its thin-walled crescent shape, it is often modeled simply as an appendage of the LV. Furthermore, PAH diagnosis is challenging because it often leaves the LV and systemic circulation largely unaffected. Several treatment strategies such as atrial septostomy, right ventricular assist devices (RVADs) or RV resynchronization therapy have been shown to improve RV function and the quality of life in patients with PAH. However, evidence of their long-term efficacy is limited and lung transplantation is still the most effective and curative treatment option. As such, the clinical need for improved diagnosis and treatment of PAH drives a strong need for increased understanding of drivers and mechanisms of RV growth and remodeling (G&R), and more generally for targeted research into RV mechanics pathology. Computational models stand out as a valuable supplement to experimental research, offering detailed analysis of the drivers and consequences of G&R, as well as a virtual test bench for exploring and refining hypotheses of growth mechanisms. In this review we summarize the current efforts towards understanding RV G&R processes using computational approaches such as reduced-order models, three dimensional (3D) finite element (FE) models, and G&R models. In addition to an overview of the relevant literature of RV computational models, we discuss how the models have contributed to increased scientific understanding and to potential clinical treatment of PAH patients. 

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5. Deep learning to quantify the pace of brain aging in relation to neurocognitive changes

   https://doi.org/10.1073/pnas.2413442122  

   Yin, Chenzhong; Imms, Phoebe; Chowdhury, Nahian F; Chaudhari, Nikhil N; Ping, Heng; Wang, Haoqing; Bogdan, Paul; Irimia, Andrei; Weiner, Michael; Aisen, Paul; et al (March 2025, Proceedings of the National Academy of Sciences)

   Brain age (BA), distinct from chronological age (CA), can be estimated from MRIs to evaluate neuroanatomic aging in cognitively normal (CN) individuals. BA, however, is a cross-sectional measure that summarizes cumulative neuroanatomic aging since birth. Thus, it conveys poorly recent or contemporaneous aging trends, which can be better quantified by the (temporal) pace P of brain aging. Many approaches to map P, however, rely on quantifying DNA methylation in whole-blood cells, which the blood–brain barrier separates from neural brain cells. We introduce a three-dimensional convolutional neural network (3D-CNN) to estimate P noninvasively from longitudinal MRI. Our longitudinal model (LM) is trained on MRIs from 2,055 CN adults, validated in 1,304 CN adults, and further applied to an independent cohort of 104 CN adults and 140 patients with Alzheimer’s disease (AD). In its test set, the LM computes P with a mean absolute error (MAE) of 0.16 y (7% mean error). This significantly outperforms the most accurate cross-sectional model, whose MAE of 1.85 y has 83% error. By synergizing the LM with an interpretable CNN saliency approach, we map anatomic variations in regional brain aging rates that differ according to sex, decade of life, and neurocognitive status. LM estimates of P are significantly associated with changes in cognitive functioning across domains. This underscores the LM’s ability to estimate P in a way that captures the relationship between neuroanatomic and neurocognitive aging. This research complements existing strategies for AD risk assessment that estimate individuals’ rates of adverse cognitive change with age. 

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