Large Vessel Flow Research Articles

Study of age-related retinal hemodynamic changes by laser speckle flowgraphy

Background: Diagnostics of hemodynamic changes is important both for clarifying the features of the course of pathological process of many ophthalmic diseases and for optimizing treatment tactics. Laser speckle flowgraphy (LSFG) is a new non-invasive method for quantitative assessment of retinal blood flow. Aim: To study age-related changes of pulse waves both in large blood vessels and microvasculature in the optic nerve head and macula by laser speckle flowgraphy. Materials and methods: Age-related changes in blood flow were studied in 60 healthy volunteers using LSFG-RetFlow. We analyzed MBR — main parameter of pulse wave assessed by the laser speckle flowgraphy and also another 8 pulse wave parameters for large vessels and microvasculature in the areas of optic nerve head and macula. Results: The study revealed statistically significant (p ≤ 0.05) age-related changes in pulse waves for most parameters under study. In the large vessels of the optic disc blood flow dropped after 60 years, while in the microvasculature it decreased progradiently in the groups older than 40 and 60 years. In the macular region, blood flow in large vessels and microvasculature decreased mainly in the group aged over 61. Age-related changes in pulse wave parameters were unidirectional for both large vessels and microvasculature; trends were similar in both areas under investigation. Conclusions: The study demonstrated statistically significant (age-related changes in most laser speckle flowgraphy pulse wave parameters. The MBR, MV (MBR of Vascular area), MT (MBR of Tissue area) indicators are most informative in the ophthalmic hemodinamic screening. The study of another pulse wave parameters seems sufficient for the general MBR.

Modeling hyperthermia-based prostate cancer treatment in the presence of core-shell nanoparticles and large blood vessels under different ultrasound sonication patterns

The use of nanoparticles, as enhancing agents to transform ultrasound energy into heat for tumor destruction, is a promising approach to improve the efficacy of thermal-based cancer therapies. This study aimed to evaluate the effectiveness of core-shell type nanoparticles and the heat loss due to blood flow in large vessels under different patterns of ultrasound sonication in the hyperthermia-based treatment of the prostate cancer. For this purpose, the ultrasound attenuation coefficient in the prostate tumor embedded with nanoparticles was calculated using a scattering theory that was developed for core-shell type particles. Using the attenuation coefficient and the linear pressure wave equation, the acoustic power dissipated per unit volume of a three-dimensional (3D) model of the prostate tumor and its surrounding tissues was calculated. By simultaneous solving the bioheat, the convective energy, the continuity, the Navier-Stokes, and the thermal dose equations, the temperature and thermal dose distribution were computed in the model. The attenuation coefficient of the tumor showed a decreasing trend with increasing the thickness of the silica shell coating the magnetite or titania core. The capability of nanoparticles to enhance heat production in the medium was directly, and the blood flow heat loss was inversely, related to the degree of focus of the ultrasound beam. The thermal response of the tumor was influenced by its size and geometry, as well as the acoustic intensity. Titania nanoparticles were more efficient than the magnetite nanoparticles in ultrasound attenuation and heat production in the medium. Our findings can be useful in understanding the factors affecting the hyperthermia-based treatment of the prostate cancer using a combination of ultrasound and nanoparticles.

Analysis of the directional and spectral distributions of kinetic energy in aortic blood flow

It has been recognized that blood flow in large vessels, such as the aorta, may undergo a transition to turbulent flow in the presence of cardiovascular disorders, while flow in the healthy aorta is perceived to be laminar under normal physiological conditions. However, this perception has been challenged by several studies, highlighting the need to consider more fundamental flow characterizations. The present study aims to provide a comprehensive analysis of the directional and spectral distributions of kinetic energy in aortic flows under normal and pathological conditions. For this purpose, large-eddy simulation results for two patient-specific aortas, representing a healthy aorta and an aorta with aortic valve stenosis, respectively, were analyzed by decomposing the resolved transient velocity fields into directional and frequency components. It is shown that fundamental characteristics, such as the distinctive role of harmonics of the cardiac cycle as well as intermediate frequencies, indicate complex flow structures and turbulence over the entire thoracic aorta in both cases. The high-frequency components of kinetic energy are found to decrease by more than one order of magnitude from regions associated with complex flow features to the descending aorta. In conclusion, the capability of such analyses to effectively describe complex aortic blood flow at physiological and pathological conditions is demonstrated and motivates further efforts to achieve a more fundamental understanding of the true nature of aortic blood flow.

The influence of post-COVID-19 syndrome on microcirculation of the optic nerve head among patients with primary open-angle glaucoma

BACKGROUND: Glaucoma is one of the leading causes of blindness in the world. This is a multifactorial ophthalmopathology, which also results from impaired microcirculation in the optic nerve. One of the diseases affecting ocular blood flow is acute coronavirus infection (COVID-19). AIM: The aim of this study is the assessment of blood flow parameters of the optic nerve head in patients with primary open-angle glaucoma (POAG) against the background of post-COVID-19 syndrome using laser speckle flowgraphy. MATERIALS AND METHODS: The study included 40 patients with advanced stage primary open-angle glaucoma who had COVID-19 within the previous 3 months. Patients were divided into 2 subgroups depending on the severity of the disease. The comparison group consisted of 20 individuals with an advanced stage of primary open-angle glaucoma who did not have COVID-19. All subjects were over 60 years old and had normal blood pressure parameters. Optic nerve head blood flow was measured using the LSFG-NAVI device (Japan) and assessed by LSFG Analyzer software. MBR parameters (MA, MV and MT), as well as pulse wave indicators (Skew, BOS, BOT, RR, FR, FAI, ATI and RI) were analyzed. RESULTS: The most significant decrease was found for the MV and MT parameters, reflecting the blood flow in large vessels and the microvasculature of the optic disc. MV decrease by 20%, MT — by 23%, MA — by 16% were noted, as well as pulse wave parameter changes, in patients with an advanced stage of primary open-angle glaucoma, post-COVID syndrome after moderate COVID-19 compared with patients with an advanced stage of primary open-angle glaucoma who did not have COVID-19 (p ≤ 0.05). CONCLUSIONS: Laser speckle flowgraphy allows rapid and effective assessment of ocular blood flow. Parameters estimated at the examination may be considered as new biomarkers for the detection and evaluation of vascular diseases.

Abstract WMP79: Stroke Risk Prediction In Symptomatic Anterior Circulation ICAS: Post Hoc Analysis Of Regional QMRA Flow From The MYRIAD Study

Introduction: Intracranial atherosclerotic disease (ICAD) remains a major source of stroke worldwide, with high recurrence risk. Prior evaluation of posterior circulation ICAD patients enrolled in the prospective VERiTAS and MYRIAD studies revealed regional hypoperfusion, assessed by large vessel flow measurements using quantitative MRA (QMRA), predicts subsequent vertebrobasilar stroke risk. We examined whether a similar approach to regional flow assessment using QMRA predicted stroke risk in anterior circulation ICAD patients enrolled in MYRIAD. Methods: MYRIAD enrolled patients with recent TIA or stroke attributable to 50-99% stenosis of proximal intracranial artery; the primary outcome was ischemic stroke in the territory of the stenotic artery with 1 year of follow-up. Secondary outcomes included new in-territory infarcts on MRI at 6-8 weeks. Flow was measured in the major intracranial arteries at baseline using QMRA. We designated patients as low- or normal-flow status based on an algorithm assessing distal flow and collateral capacity using age-normalized MCA and hemispheric (aggregate of ipsilateral ACA, MCA, and PCA) flows. Different thresholds for flow status categorization were tested to determine the optimal algorithm for stroke risk prediction. Results: Of 73 enrolled subjects with symptomatic anterior circulation ICAD, 7 (9.6%) patients had recurrent stroke. Z-score thresholds for age-normalized flow ranging from -0.5 to -1.5 were examined. The optimal thresholds identified were as follows: -1 for the MCA and -0.75 for hemispheric flow. 24 (33%) patients were categorized as low-flow status based on these thresholds; recurrent stroke occurred in 21% of low-flow patients vs. 4% of normal-flow patients (OR 6.2 (95% CI 1.1-34.7, p=0.04). However, flow status was not predictive of recurrent infarct on imaging among 61 patients with 6-8 week MRI (32% in low-flow vs. 26% in normal-flow patients). Conclusions: Similar to the predictive value in the posterior circulation, distal flow status assessed through QMRA regional flow measurement appears to be predictive for recurrent clinical (but not imaging-based) stroke. Identification of high-risk patients has implications for future investigation of therapeutic interventions.

Ultrafast ultrasound localization microscopy method for spinal cord mircovasculature imaging

Function of spinal cord is crucial to nerve conduction pathway. Traumatic spinal cord injury often results in a vasculature disruption after primary insult and further leads to abnormal responses of the intact vessels in neighboring tissue during secondary injury. Therefore, the vasculature and blood supply play significant roles in evaluating the spinal cord function . Ultrasound localization microscopy (ULM) overcomes the shortcomings of extensively used angiography, such as computed tomography angiography (CTA) and magnetic resonance angiography (MRA), in terms of limited resolution, radiation and poor-portability, which meets the needs of comprehensive intraoperative examination and prognosis tracking. In this study, an L22-14vX probe with a transmission frequency of 15.625 MHz is utilized, yielding an imaging wavelength of 100 μm. The ULM is conducted based on ultrafast ultrasound technology with multiple tilted plane-wave illuminations. Robust principal component analysis (RPCA) based spatial-temporal clutter filtering method is used for separating the microbubble signals from tissue signals and high frequency noise. Through microbubble localization, trajectory tracking and mapping, subwavelength super-resolution ultrasound imaging is finally achieved. The whole process of microbubble localization and vessel reconstruction are monitored through measuring the time dependent microbubble detections and saturation. Saturation curve corresponds to the time dependent total area covered by microbubble detections on the image. Quantification analysis is carried out for evaluating the imaging results including resolution measurements based on the Fourier ring correlation (FRC) and full-width at half-maximum (FWHM). The <i>i</i><i>n-vivo</i> experimental results show that ULM can be used to obtain super-resolution vasculature imaging in rat spinal cord. The velocity distributed from 1 mm/s to 50 mm/s can be detected. Within the same vessel, the velocity of a point is inversely correlated with the distance from the point to the center of the vessel. The velocity in the center of the vessel is larger than that at the wall of the vessel. The larger vessels support higher flow in the center of the vessel. The FWHM results indicate that ultrafast Doppler displays vessels in diameters between 135 μm and 270 μm while ULM displays them in diameters between 28 μm and 35 μm. The FRC-based resolution evaluation shows that the ULM achieves a super resolution of 16 μm, much less than the imaging wavelength of 100 μm. Yet, long acquisition time is required to detect microbubbles in the smallest vessels, leading to long reconstruction of the microvasculature, which is still a problem worth studying . Compromise between saturation and acquisition time needs considering. Generally speaking, microbubbles are more likely to flow in large vessels, leading to relatively short reconstruction time of large vessels. When saturation curve almost converges, the imaging improvement with new vessels is not so significant that the detail sacrifice of some small microvessels can reduce acquisition time (i.e. most of microvasculature can still be gained when the saturation curve does not converge). Besides, the increase of microbubble concentration and advanced track identification and extraction may also accelerate the saturation rate of convergence with acquisition time decreasing. In conclusion, ULM can be used to obtain a super-resolution imaging of spinal cord microvasculature, giving a 10-fold improvement in resolution in comparison with ultrafast Doppler imaging. Relevant results can facilitate the super-resolution ULM imaging of spinal cord which may promote the function diagnosis, treatment intervention, disability prevention, and prognosis recovery of spinal cord injury.

A nonlinear multi-scale model for blood circulation in a realistic vascular system.

In the last decade, numerical models have become an increasingly important tool in biological and medical science. Numerical simulations contribute to a deeper understanding of physiology and are a powerful tool for better diagnostics and treatment. In this paper, a nonlinear multi-scale model framework is developed for blood flow distribution in the full vascular system of an organ. We couple a quasi one-dimensional vascular graph model to represent blood flow in larger vessels and a porous media model to describe flow in smaller vessels and capillary bed. The vascular model is based on Poiseuille’s Law, with pressure correction by elasticity and pressure drop estimation at vessels' junctions. The porous capillary bed is modelled as a two-compartment domain (artery and venous) using Darcy’s Law. The fluid exchange between the artery and venous capillary bed compartments is defined as blood perfusion. The numerical experiments show that the proposed model for blood circulation: (i) is closely dependent on the structure and parameters of both the larger vessels and of the capillary bed, and (ii) provides a realistic blood circulation in the organ. The advantage of the proposed model is that it is complex enough to reliably capture the main underlying physiological function, yet highly flexible as it offers the possibility of incorporating various local effects. Furthermore, the numerical implementation of the model is straightforward and allows for simulations on a regular desktop computer.

Data Assimilation by Stochastic Ensemble Kalman Filtering to Enhance Turbulent Cardiovascular Flow Data From Under-Resolved Observations.

We propose a data assimilation methodology that can be used to enhance the spatial and temporal resolution of voxel-based data as it may be obtained from biomedical imaging modalities. It can be used to improve the assessment of turbulent blood flow in large vessels by combining observed data with a computational fluid dynamics solver. The methodology is based on a Stochastic Ensemble Kalman Filter (SEnKF) approach and geared toward pulsatile and turbulent flow configurations. We describe the observed flow fields by a mean value and its covariance. These flow fields are combined with forecasts obtained from a direct numerical simulation of the flow field. The method is validated against canonical pulsatile and turbulent flows. Finally, it is applied to a clinically relevant configuration, namely the flow downstream of a bioprosthetic valve in an aorta phantom. It is demonstrated how the 4D flow field obtained from experimental observations can be enhanced by the data assimilation algorithm. Results show that the presented method is promising for future use with in vivo data from 4D Flow Magnetic Resonance Imaging (4D Flow MRI). 4D Flow MRI returns spatially and temporally averaged flow fields that are limited by the spatial and the temporal resolution of the tool. These averaged flow fields and the associated uncertainty might be used as observation data in the context of the proposed methodology.

On the ability to exploit signal fluctuations in pseudocontinuous arterial spin labeling for inferring the major flow territories from a traditional perfusion scan

In arterial spin labeling (ASL) a magnetic label is applied to the flowing blood in feeding arteries allowing depiction of cerebral perfusion maps. The labeling efficiency depends, however, on blood velocity and local field inhomogeneities and is, therefore, not constant over time. In this work, we investigate the ability of statistical methods used in functional connectivity research to infer flow territory information from traditional pseudo-continuous ASL (pCASL) scans by exploiting artery-specific signal fluctuations. By applying an additional gradient during labeling the minimum amount of signal fluctuation that allows discrimination of the main flow territories is determined. The following three approaches were tested for their performance on inferring the large vessel flow territories of the brain: a general linear model (GLM), an independent component analysis (ICA) and t-stochastic neighbor embedding. Furthermore, to investigate the effect of large vessel pathology, standard ASL scans of three patients with a unilateral stenosis (>70%) of one of the internal carotid arteries were retrospectively analyzed using ICA and t-SNE. Our results suggest that the amount of natural-occurring variation in labeling efficiency is insufficient to determine large vessel flow territories. When applying additional vessel-encoded gradients these methods are able to distinguish flow territories from one another, but this would result in approximately 8.5% lower perfusion signal and thus also a reduction in SNR of the same magnitude.

Spectral diffusion analysis of kidney intravoxel incoherent motion MRI in healthy volunteers and patients with renal pathologies.

To assess the feasibility of measuring tubular and vascular signal fractions in the human kidney using nonnegative least-square (NNLS) analysis of intravoxel incoherent motion data collected in healthy volunteers and patients with renal pathologies. MR imaging was performed at 3 Tesla in 12 healthy subjects and 3 patients with various kidney pathologies (fibrotic kidney disease, failed renal graft, and renal masses). Relative signal fractions f and mean diffusivities of the diffusion components in the cortex, medulla, and renal lesions were obtained using the regularized NNLS fitting of the intravoxel incoherent motion data. Test-retest repeatability of the NNLS approach was tested in 5 volunteers scanned twice. In the healthy kidneys, the NNLS method yielded diffusion spectra with 3 distinguishable components that may be linked to the slow tissue water diffusion, intermediate tubular and vascular flow, and fast blood flow in larger vessels with the relative signal fractions, fslow , finterm and ffast , respectively. In the pathological kidneys, the diffusion spectra varied substantially from those acquired in the healthy kidneys. Overall, the renal cyst showed substantially higher finterm and lower fslow , whereas the fibrotic kidney, failed renal graft, and renal cell carcinoma demonstrated the opposite trend. NNLS-based intravoxel incoherent motion could potentially become a valuable tool in assessing changes in tubular and vascular volume fractions under pathophysiological conditions.

Perfusion-MRI is a Poor Indicator of Hemodynamic Compromise in Vertebrobasilar Disease in the VERiTAS Study.

Dynamic susceptibility perfusion MR imaging (DSC MRP) has been used to assess changes in cerebral perfusion attributable to vascular stenosis or occlusion that may predict stroke risk. However, DSC MRP is not validated for identifying hemodynamic compromise in the posterior circulation. We investigated the clinical utility of DSC MRP in vertebrobasilar (VB) atherosclerotic disease in the observational VERiTAS study. VERiTAS enrolled patients with symptomatic ≥50% VB stenosis/occlusion. Posterior circulation hemodynamic status was designated as low or normal based on large vessel flow measured using quantitative magnetic resonance angiography (QMRA) and was predictive of future stroke risk. In this study, DSC MRP conducted concurrently with QMRA was used to evaluate posterior circulation perfusion. The primary outcome was the mean transit time (MTT) and relative cerebral blood volume (rCBV) in the posterior circulation normalized to the anterior circulation, compared between patients with low and normal blood flow as determined on QMRA. Twenty-six subjects had 47 DSC MRP studies for review. There was no statistically or clinically significant difference in the rCBV ratio (1.02 vs. .96 P = .89), or MTT ratio (1.04 vs. 1.04 P = .96) relative to normal or low VB territory flow. In this study, we did not find that DSC MRP adequately distinguished between patients with low or normal flow status based on large-vessel flow measurements.

Natural History of Hemodynamics in Vertebrobasilar Disease: Temporal Changes in the VERiTAS Study Cohort.

The role of regional hypoperfusion as a contributor to stroke risk in atherosclerotic vertebrobasilar disease has recently been confirmed by the observational VERiTAS (Vertebrobasilar Flow Evaluation and Risk of Transient Ischemic Attack and Stroke) Study. We examined the stability of hemodynamic status over time and its relationship to stroke risk in patients from this prospective cohort. VERiTAS enrolled patients with recently symptomatic ≥50% atherosclerotic stenosis/occlusion of vertebral and/or basilar arteries. Large vessel flow in the vertebrobasilar territory was assessed using quantitative magnetic resonance angiography, and patients were designated as low or normal flow based on distal territory regional flow, incorporating collateral capacity. Patients underwent standard medical management and follow-up for primary outcome event of vertebrobasilar territory stroke. Quantitative magnetic resonance angiography imaging was repeated at 6, 12, and 24 months. Flow status over time was examined relative to baseline and relative to subsequent stroke risk using a cause-specific proportional hazard model, with flow status treated as a time-varying covariate. Mean blood pressure was examined to assess for association with changes in flow status. Over 19±8 months of follow-up, 132 follow-up quantitative magnetic resonance angiography studies were performed in 58 of the 72 enrolled patients. Of the 13 patients with serial imaging who had low flow at baseline, 7 (54%) had improvement to normal flow at the last follow-up. Of the 45 patients who had normal flow at baseline, 3 (7%) converted to low flow at the last follow-up. The mean blood pressure did not differ in patients with or without changes in flow status. The time-varying flow status remained a strong predictor of subsequent stroke (hazard ratio, 10.3 [95% CI, 2.2-48.7]). There is potential both for improvement and worsening of hemodynamics in patients with atherosclerotic vertebrobasilar disease. Flow status, both at baseline and over time, is a risk factor for subsequent stroke, thus serving as an important prognostic marker. Registration: URL: https://clinicaltrials.gov. Unique identifier: NCT00590980.

EARLY MARKERS OF DIAGNOSIS FETAL GROWTH RESTRICTION SYNDROME

The article presents the effectiveness of Dopplerometry for assessing blood flow in large vessels, including the umbilical, uterine artery and middle cerebral artery, 90 women were examined in the second trimester, and 45 women showed signs of placental insufficiency, such as fetal growth restriction syndrome at 28-34 weeks. The results of the study showed that 23 (51.1%) women had signs of subcompensated insufficiency of uteroplacental blood flow, and 11 (24.4%) women showed signs of fetal-placental blood flow. The study of the uteroplacental-fetal blood flow allows early detection of early signs of impairment in the fetoplacental system and its timely correction.

From Anatomy to Functional and Molecular Biomarker Imaging and Therapy: Ultrasound Is Safe, Ultrafast, Portable, and Inexpensive.

Ultrasound is the most widely used medical imaging modality worldwide. It is abundant, extremely safe, portable, and inexpensive. In this review, we consider some of the current development trends for ultrasound imaging, which build upon its current strength and the popularity it experiences among medical imaging professional users.Ultrasound has rapidly expanded beyond traditional radiology departments and cardiology practices. Computing power and data processing capabilities of commonly available electronics put ultrasound systems in a lab coat pocket or on a user's mobile phone. Taking advantage of new contributions and discoveries in ultrasound physics, signal processing algorithms, and electronics, the performance of ultrasound systems and transducers have progressed in terms of them becoming smaller, with higher imaging performance, and having lower cost. Ultrasound operates in real time, now at ultrafast speeds; kilohertz frame rates are already achieved by many systems.Ultrasound has progressed beyond anatomical imaging and monitoring blood flow in large vessels. With clinical approval of ultrasound contrast agents (gas-filled microbubbles) that are administered in the bloodstream, tissue perfusion studies are now routine. Through the use of modern ultrasound pulse sequences, individual microbubbles, with subpicogram mass, can be detected and observed in real time, many centimeters deep in the body. Ultrasound imaging has broken the wavelength barrier; by tracking positions of microbubbles within the vasculature, superresolution imaging has been made possible. Ultrasound can now trace the smallest vessels and capillaries, and obtain blood velocity data in those vessels.Molecular ultrasound imaging has now moved closer to clinic; the use of microbubbles with a specific affinity to endothelial biomarkers allows selective accumulation and retention of ultrasound contrast in the areas of ischemic injury, inflammation, or neoangiogenesis. This will aid in noninvasive molecular imaging and may provide additional help with real-time guidance of biopsy, surgery, and ablation procedures.The ultrasound field can be tightly focused inside the body, many centimeters deep, with millimeter precision, and ablate lesions by energy deposition, with thermal or mechanical bioeffects. Some of such treatments are already in clinical use, with more indications progressing through the clinical trial stage. In conjunction with intravascular microbubbles, focused ultrasound can be used for tissue-specific drug delivery; localized triggered release of sequestered drugs from particles in the bloodstream may take time to get to clinic. A combination of intravascular microbubbles with circulating drug and low-power ultrasound allows transient opening of vascular endothelial barriers, including blood-brain barrier; this approach has reached clinical trial stage. Therefore, the drugs that normally would not be getting to the target tissue in the brain will now have an opportunity to produce therapeutic efficacy.Overall, medical ultrasound is developing at a brisk rate, even in an environment where other imaging modalities are also advancing rapidly and may be considered more lucrative. With all the current advances that we discuss, and many more to come, ultrasound may help solve many problems that modern medicine is facing.

Backflow stabilization by deconvolution-based large eddy simulation modeling

In the numerical simulations of incompressible fluids, the occurrence of incoming flows through outlet boundaries where Neumann conditions are prescribed may introduce the numerical instability known as the backflow instability. This backflow instability is related to the nonlinear convective term and is often challenging the numerical simulation of the blood flow in large vessels. In fact, the alternation of systole and diastole induces backflows at the outlets, which are usually Neumann boundaries since the lack of velocity data requires the prescription of traction/pressure conditions. The Reynolds numbers that trigger the backflow instability are generally moderate (in the range of a few hundreds and above).In this work, we prove that a particular Large Eddy Simulation (LES) model implicitly stabilizes the backflow instability. This LES model uses deconvolution filters and is the basis of the so-called Evolve-Filter-Relax scheme recently introduced by Layton, Rebholz and their collaborators as an effective alternative to Direct Numerical Simulations for the moderate or large Reynolds number flow. With a judicious selection of the parameters of this LES scheme, it is possible to suppress the term that triggers the numerical backflow instability, so to obtain reliable and efficient numerical simulations. This is particularly attractive in computational clinical studies, where many cases need to be studied in a relatively short time.We provide a rigorous proof of our statement and numerical evidence that corroborates the theory on both idealized and realistic cases. For the latter, we consider a patient-specific aortic aneurysm geometry. Aortic simulations feature Reynolds numbers and flow regimes that particularly benefit from this serendipity (aka ‘two-birds-one-stone’) circumstance, where a LES modeling is stabilizing a numerical artifact.

The one-dimensional model of non-Newtonian hemodynamics

The one-dimensional model of the blood flow in large vessels is considered. The non-Newtonian nature of blood is modeled by the friction force and Boussinesq coefficient value. The power law rheological model of fluid is used. The comparison with the models of blood as ideal and Newtonian fluid is realized. The nonlinear problems of single-pulse propagation in a single vessel and in a vessel with bifurcation are considered. It is demonstrated, that non-Newtonian effects play an important role in the obtained solutions.

Flow phantom for contrast enhanced ultrasound research, device validation, and clinical training

Phantoms are an important part of ultrasound research, instrument development, and clinical training. There are, however, no standardized phantoms for contrast enhanced ultrasound. Phantoms typically include either tubes to mimic flow in larger vessels or dialysis tubing to mimic perfusion in the capillary bed. These approaches fail to mimic the full range of flow regimes and tissue scattering observed in the body during imaging. To address some of these limitations, we designed a phantom that integrates flow in both the macro- and microcirculation with physiological tissue backscatter, attenuation, and sound speed and that can be customized to simultaneously mimic flow in normal and malignant tissues. A variety of sponges and foams were considered. Acceptable materials were fit in a custom-built flow chamber and imaged with a commercially available ultrasound system. A polyvinyl alcohol (PVA) sponge was deemed to be a suitable phantom material. PVA has a sound speed of 1490 m/s and attenuation coefficient of 0.6 dB/cm/MHz. After introducing a contrast agent into the flow system, the agent could be visualized rapidly entering the flow inlets, perfusing slowly through the sponge, and rapidly exiting through the flow outlets. [Funded by Philips Ultrasound and the Life Sciences Discovery Fund No. 3292512.]Phantoms are an important part of ultrasound research, instrument development, and clinical training. There are, however, no standardized phantoms for contrast enhanced ultrasound. Phantoms typically include either tubes to mimic flow in larger vessels or dialysis tubing to mimic perfusion in the capillary bed. These approaches fail to mimic the full range of flow regimes and tissue scattering observed in the body during imaging. To address some of these limitations, we designed a phantom that integrates flow in both the macro- and microcirculation with physiological tissue backscatter, attenuation, and sound speed and that can be customized to simultaneously mimic flow in normal and malignant tissues. A variety of sponges and foams were considered. Acceptable materials were fit in a custom-built flow chamber and imaged with a commercially available ultrasound system. A polyvinyl alcohol (PVA) sponge was deemed to be a suitable phantom material. PVA has a sound speed of 1490 m/s and attenuation coefficien...

Abstract TP91: Perfusion-weighted Magnetic Resonance Imaging is a Poor Indicator of Hemodynamic Compromise in Vertebrobasilar Disease

Introduction: Perfusion-weighted magnetic resonance imaging (MRP) has been used to assess changes in cerebral perfusion attributable to vascular stenosis or occlusion that may predict stroke risk. The ability of MRP to identify hemodynamic compromise in the posterior circulation, however, has not been well established. The observational Vertebrobasilar Flow Evaluation and Risk of Transient Ischemic Attack and Stroke (VERiTAS) study has previously demonstrated that flow status determined through large vessel flow measurements with quantitative magnetic resonance angiography (QMRA) predicts stroke risk in vertebrobasilar disease. We examined whether MRP parameters correlated with QMRA assessment of flow compromise in the VERiTAS cohort. Methods: VERiTAS enrolled patients with recent vertebrobasilar transient ischemic attack or stroke and ≥50% atherosclerotic stenosis or occlusion in vertebral and/or basilar arteries. Hemodynamic status using vertebrobasilar large vessel flow was measured using QMRA, and patients were designated as low or normal flow based on distal territory regional flow, incorporating collateral capacity. Dynamic susceptibility contrast MRP was performed concurrently with QMRA. Mean transit time (MTT) in the posterior cerebral artery (PCA) territory was used to evaluate posterior circulation perfusion. To normalize the values, an MTT ratio was calculated in reference to the anterior circulation (mean of the anterior cerebral artery (ACA) and middle cerebral artery (MCA) territories). The PCA to ACA/MCA MTT ratio from MRP was then assessed relative to flow status (normal vs. low) from QMRA. Results: Of the 72 enrolled subjects, 23 had MRP data available for review. On initial QMRA designation, 19 subjects were designated as normal flow vs. 4 as low flow. The mean MTT ratios for patients with normal vs. low flow were 1.02 (SD=0.05) vs.1.04 (SD=0.04), respectively (p=0.55, t test; p=0.50, Wilcoxon rank sum test). Among the subgroup of 23 patients, 1 patient with low flow, and MTT ratio of 1.00, experienced a recurrent stroke. Conclusions: These results suggest that MRP is a poor indicator of actual hemodynamic compromise in vertebrobasilar disease and is not a reliable substitute for large vessel flow measurements.

Hypoperfusion Symptoms Poorly Predict Hemodynamic Compromise and Stroke Risk in Vertebrobasilar Disease.

Background and Purpose- Cerebral hypoperfusion symptoms (defined as symptoms related to change in position, effort or exertion, or recent change in antihypertensive medication) have been used in stroke studies as a surrogate for detecting hemodynamic compromise. However, the validity of these symptoms in identifying flow compromise in patients has not been well established. We examined whether hypoperfusion symptoms correlated with quantitative measurements of flow compromise in the prospective, observational VERiTAS study (Vertebrobasilar Flow Evaluation and Risk of Transient Ischemic Attack and Stroke). Methods- VERiTAS enrolled patients with recent vertebrobasilar transient ischemic attack or stroke and ≥50% atherosclerotic stenosis or occlusion in vertebral or basilar arteries. Hemodynamic status using vertebrobasilar large vessel flow was measured using quantitative magnetic resonance angiography, and patients were designated as low, borderline, or normal flow based on distal territory regional flow, incorporating collateral capacity. The presence of qualifying event hypoperfusion symptoms was assessed relative to the quantitatively determined flow status (normal versus borderline/low) and also examined as a predictor of subsequent stroke risk. Results- Of the 72 enrolled subjects, 66 had data on hypoperfusion symptoms available. On initial quantitative magnetic resonance angiography designation, 43 subjects were designated as normal flow versus 23 subjects designated as low flow (n=16) or borderline flow (n=7). Of these, 5 (11.6%) normal flow and 3 (13.0%) low/borderline flow subjects reported at least one qualifying event hypoperfusion symptom ( P=0.99, Fisher exact test). Hypoperfusion symptoms had a positive predictive value of 37.5% and negative predictive value of 65.5% for low/borderline flow status. Compared with flow status, which strongly predicted subsequent stroke risk, hypoperfusion symptoms were not associated with stroke outcome ( P=0.87, log-rank test). Conclusions- These results suggest that hypoperfusion symptoms alone correlate poorly with actual hemodynamic compromise as assessed by quantitative magnetic resonance angiography and subsequent stroke risk in vertebrobasilar disease, and are not a reliable surrogate for flow measurement. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifier: NCT00590980.

The first integral method for two fractional non-linear biological models

Travelling wave solutions of the space and time fractional models for non-linear blood flow in large vessels and Deoxyribonucleic acid (DNA) molecule dynamics defined in the sense of Jumarie's modified Riemann-Liouville derivative via the first integral method are presented in this study. A fractional complex transformation was applied to turn the fractional biological models into an equivalent integer order ordinary differential equation. The validity of the solutions to the fractional biological models obtained with first integral method was achieved by putting them back into the models. We observed that introducing fractional order to the biological models changes the nature of the solution.