Haemodynamic dependence of mechano-genetic evolution of the cardiovascular system in Japanese medaka.

The progression of cardiac gene expression-wall shear stress (WSS) interplay is critical to identifying developmental defects during cardiovascular morphogenesis. However, mechano-genetics from the embryonic to larval stages are poorly understood in vertebrates. We quantified peak WSS in the heart and tail vessels of Japanese medaka from 3 days post fertilization (dpf) to 14 dpf using in vivo micro-particle image velocimetry flow measurements, and in parallel analysed the expression of five cardiac genes (fgf8, hoxb6b, bmp4, nkx2.5, smyd1). Here, we report that WSS in the atrioventricular canal (AVC), ventricular outflow tract (OFT), and the caudal vessels in medaka peak with inflection points at 6 dpf and 10-11 dpf instead of a monotonic trend. Retrograde flows are captured at the AVC and OFT of the medaka heart for the first time. In addition, all genes were upregulated at 3 dpf and 7 dpf, indicating a possible correlation between the two, with the cardiac gene upregulation preceding WSS increase in order to facilitate cardiac wall remodelling.

A Wavelet Approach to the Estimation of Left Ventricular Early Filling Wave Propagation Velocity from Color M-Mode Echocardiograms.

A new approach to calculating left ventricular (LV) early filling propagation velocity (VP) from color M-mode echocardiograms using wavelet analysis is described. Current methods for measuring VP do not account for the spatiotemporal variation in VP. They are confined by empirical assumptions and user inputs that hinder the accuracy of VP, limiting its clinical utility. We evaluated three methods for measuring LV early filling: conventional VP, the strength of propagation (VS) and wavelet propagation velocity (VW) determined from the most energetically significant wave (peak VW). Group A comprised 125 patients (n = 50 normal filling, n = 25 impaired relaxation, n = 25 pseudonormal filling and n = 25 restrictive filling), and group B comprised 69 patients (n = 32 normal, n = 15 dilated and n = 22 hypertrophic). Peak VW most accurately distinguished normal from diseased patients. For group A, the area under the receiver operating characteristic curve was 0.92 for peak VW versus 0.62 for VP, 0.63 for VS and 0.58 for intraventricular pressure difference. These correspond to a 50%-70% improvement in classification ability. Similar improvements were measured in group B. Peak VW may provide a more accurate evaluation of diastolic function than standard methods and enable better diagnostic classification of patients with diastolic dysfunction.

Mixture theory modeling for characterizing solute transport in breast tumor tissues.

BACKGROUND: Tumor numerical models have been used to quantify solute transport with a single capillary embedded in an infinite tumor expanse, but measurements from different mammalian tumors suggest that a tissue containing a single capillary with an infinite intercapillary distance assumption is not physiological. The present study aims to investigate the limits of the intercapillary distance within which nanoparticle transport resembles solute extravasation in a breast tumor model as a function of the solute size, the intercapillary separation, and the flow direction in microvessels. METHODS: Solute transport is modeled in a breast tumor for different vascular configurations using mixture theory. A comparison of a single capillary configuration (SBC) with two parallel cylindrical blood vessels (2 BC) and a lymph vessel parallel to a blood vessel (BC_LC) embedded in the tissue cylinder is performed for five solute molecular weights between 0.1 kDa and 70 kDa. The effects of counter flow (CN) versus co-current flow (CO) on the solute accumulation were also investigated and the scaling of solute accumulation-decay time and concentration was explored. RESULTS: We found that the presence of a second capillary reduces the extravascular concentration compared to a single capillary and this reduction is enhanced by the presence of a lymph vessel. Varying the intercapillary distance with respect to vessel diameter shows a deviation of 10-30% concentration for 2 BC and 45-60% concentration for BC_LC configuration compared to the reference SBC configuration. Finally, we introduce a non-dimensional time scale that captures the concentration as a function of the transport and geometric parameters. We find that the peak solute concentration in the tissue space occurs at a non-dimensional time, T peak ∗ = 0.027 ± 0.018, irrespective of the solute size, tissue architecture, and microvessel flow direction. CONCLUSIONS: This work suggests that the knowledge of such a unique non-dimensional time would allow estimation of the time window at which solute concentration in tissue peaks. Hence this can aid in the design of future therapeutic efficacy studies as an example for triggering drug release or laser excitation in the case of photothermal therapies.

Imaging of small animal peripheral artery disease models: recent advancements and translational potential.

Peripheral artery disease (PAD) is a broad disorder encompassing multiple forms of arterial disease outside of the heart. As such, PAD development is a multifactorial process with a variety of manifestations. For example, aneurysms are pathological expansions of an artery that can lead to rupture, while ischemic atherosclerosis reduces blood flow, increasing the risk of claudication, poor wound healing, limb amputation, and stroke. Current PAD treatment is often ineffective or associated with serious risks, largely because these disorders are commonly undiagnosed or misdiagnosed. Active areas of research are focused on detecting and characterizing deleterious arterial changes at early stages using non-invasive imaging strategies, such as ultrasound, as well as emerging technologies like photoacoustic imaging. Earlier disease detection and characterization could improve interventional strategies, leading to better prognosis in PAD patients. While rodents are being used to investigate PAD pathophysiology, imaging of these animal models has been underutilized. This review focuses on structural and molecular information and disease progression revealed by recent imaging efforts of aortic, cerebral, and peripheral vascular disease models in mice, rats, and rabbits. Effective translation to humans involves better understanding of underlying PAD pathophysiology to develop novel therapeutics and apply non-invasive imaging techniques in the clinic.

Calculating intraventricular pressure difference using a multi-beat spatiotemporal reconstruction of color m-mode echocardiography.

This work aims to provide a methodology to improve the analysis of color-M-Mode (CMM) echocardiograms, as used to assess cardiac function. Specifically, we presented a methodology for the combined analysis of multiple heartbeat cycles and improve the accuracy of intraventricular pressure difference (IVPD) calculation. CMM sweep speed and heartbeat variations impact the accuracy of IVPD calculation. Proper orthogonal decomposition (POD) is used to decompose and reconstruct a representative CMM scan from multiple heartbeats, with reduced noise and improved resolution. For three demonstration subjects, at least 9 beats were recorded at sweep speeds of 25, 50, 75, 100, and 150 mm/s. For all subjects, the beats from the 25 mm/s group resulted in low IVPD (median values: 1.93, 1.94 and 3.15 mmHg) compared to the 150 mm/s group (median values: 3.67, 3.98 and 5.18 mmHg). Reconstructed heartbeats for these subjects returned IVPD of 4.74, 3.23, and 5.14 mmHg. These results demonstrate the strong dependence of IVPD on the temporal resolution and that the proposed reconstruction method can return more accurate IVPDs for low resolution CMMs. This new method was applied to 5 clinical cohorts (3 normals, 1 restrictive, and 1 hypertrophied) and returned increased median IVPD from 2.93-4.41 mmHg for Normal 1, 2.14-3.30 mmHg for Normal 2, 1.84-3.64 mmHg for Normal 3, 2.28-3.00 mmHg for restrictive and 1.56-1.69 mmHg for hypertrophied. Our results show that beat-to-beat variations and temporal resolution affect the IVPD. Our new method rectifies low resolutions and beat-to-beat variability of the CMM data and allows for more accurate IVPD measurement independent of scanner acquisition settings and beat variations.