Computational modeling of low-density lipoprotein accumulation at the carotid artery bifurcation after stenting.

Restenosis typically occurs in regions of low and oscillating wall shear stress, which also favor the accumulation of atherogenic macromolecules such as low-density lipoprotein (LDL). This study aims to evaluate LDL transport and accumulation at the carotid artery bifurcation following carotid artery stenting (CAS) by means of computational simulation. The computational model consists of coupled blood flow and LDL transport, with the latter being modeled as a dilute substance dissolved in the blood and transported by the flow through a convection-diffusion transport equation. The endothelial layer was assumed to be permeable to LDL, and the hydraulic conductivity of LDL was shear-dependent. Anatomically realistic geometric models of the carotid bifurcation were built based on pre- and post-stent computed tomography (CT) scans. The influence of stent design was investigated by virtually deploying two different types of stents (open- and closed-cell stents) into the same carotid bifurcation model. Predicted LDL concentrations were compared between the post-stent carotid models and the relatively normal contralateral model reconstructed from patient-specific CT images. Our results show elevated LDL concentration in the distal section of the stent in all post-stent models, where LDL concentration is 20 times higher than that in the contralateral carotid. Compared with the open-cell stents, the closed-cell stents have larger areas exposed to high LDL concentration, suggesting an increased risk of stent restenosis. This computational approach is readily applicable to multiple patient studies and, once fully validated against follow-up data, it can help elucidate the role of stent strut design in the development of in-stent restenosis after CAS.

Phase-contrast magnetic resonance imaging and computational fluid dynamics assessment of thoracic aorta blood flow: a literature review.

The death rate from thoracic aortic disease is on the rise and represents a growing global health concern as patients are often asymptomatic before acute events, which have devastating effects on health-related quality of life. Biomechanical factors have been found to play a major role in the development of both acquired and congenital aortic diseases. However, much is still unknown and translational benefits of this knowledge are yet to be seen. Phase-contrast cardiovascular magnetic resonance imaging of thoracic aortic blood flow has emerged as an exceptionally powerful non-invasive tool enabling visualization of complex flow patterns, and calculation of variables such as wall shear stress. This has led to multiple new findings in the areas of phenotype-dependent bicuspid valve flow patterns, thoracic aortic aneurysm formation and aortic prosthesis performance assessment. Phase-contrast cardiovascular magnetic resonance imaging has also been used in conjunction with computational fluid modelling techniques to produce even more sophisticated analyses, by allowing the calculation of haemodynamic variables with exceptional temporal and spatial resolution. Translationally, these technologies may potentially play a major role in the emergence of precision medicine and patient-specific treatments in patients with aortic disease. This clinically focused review will provide a systematic overview of key insights from published studies to date.

Flow pattern analysis in a highly stenotic patient-specific carotid bifurcation model using a turbulence model.

The aim of this study is to investigate the blood flow pattern in carotid bifurcation with a high degree of luminal stenosis, combining in vivo magnetic resonance imaging (MRI) and computational fluid dynamics (CFD). A newly developed two-equation transitional model was employed to evaluate wall shear stress (WSS) distribution and pressure drop across the stenosis, which are closely related to plaque vulnerability. A patient with an 80% left carotid stenosis was imaged using high resolution MRI, from which a patient-specific geometry was reconstructed and flow boundary conditions were acquired for CFD simulation. A transitional model was implemented to investigate the flow velocity and WSS distribution in the patient-specific model. The peak time-averaged WSS value of approximately 73 Pa was predicted by the transitional flow model, and the regions of high WSS occurred at the throat of the stenosis. High oscillatory shear index values up to 0.50 were present in a helical flow pattern from the outer wall of the internal carotid artery immediately after the throat. This study shows the potential suitability of a transitional turbulent flow model in capturing the flow phenomena in severely stenosed carotid arteries using patient-specific MRI data and provides the basis for further investigation of the links between haemodynamic variables and plaque vulnerability. It may be useful in the future for risk assessment of patients with carotid disease.

Geometric and flow features of type B aortic dissection: initial findings and comparison of medically treated and stented cases.

Uncomplicated acute type B aortic dissections are usually treated medically, but they can become acutely complicated by rapid expansion, rupture and malperfusion syndromes and in the longer term by chronic dilatation and aortic aneurysm formation. The objective of this study is to use computational fluid dynamics reconstructions of type B aortic dissections to compare geometric and haemodynamic factors between the cases selected for medical treatment and the cases selected for thoracic endovascular aortic repair (TEVAR), and to examine whether any of these factors are associated with the outcome of the medically treated group. This study includes eight type B dissection cases, with four in each group. Aortic flow analyses were carried out based on patient-specific anatomy at initial presentation before treatment. Comparisons between the two groups show that the false lumen to true lumen volume ratio is considerably higher in patients selected for TEVAR. Results from the four medically treated cases indicate that the size of the primary entry tear is the key determinant of the false lumen flow rate, which may influence the long-term outcome of medically treated patients. Potential relations between flow related parameters based on initial anatomy and subsequent anatomical changes in the medically treatment group were examined. Our initial findings based on the limited cases are that high relative residence time is a strong predictor of subsequent false lumen thrombosis, whereas pressure difference between the true and false lumen as well as the location of the largest pressure difference may be associated with the likelihood of subsequent aortic expansion.

A novel fully automated method for mitral regurgitant orifice area quantification.

BACKGROUND: Effective regurgitant orifice area (EROA) in mitral regurgitation (MR) is difficult to quantify. Clinically it is measured using the proximal isovelocity surface area (PISA) method, which is intrinsically not automatable, because it requires the operator to manually identify the mitral valve orifice. We introduce a new fully automated algorithm, ("AQURO"), which calculates EROA directly from echocardiographic colour M-mode data, without requiring operator input. METHODS: Multiple PISA measurements were compared to multiple AQURO measurements in twenty patients with MR. For PISA analysis, three mutually blinded observers measured EROA from the four stored video loops. For AQURO analysis, the software automatically processed the colour M-mode datasets and analysed the velocity field in the flow-convergence zone to extract EROA directly without any requirement for manual radius measurement. RESULTS: Reproducibility, measured by intraclass correlation (ICC), for PISA was 0.80, 0.83 and 0.83 (for 3 observers respectively). Reproducibility for AQURO was 0.97. Agreement between replicate measurements calculated using Bland-Altman standard deviation of difference (SDD) was 21,17 and 17mm(2)for the three respective observers viewing independent video loops using PISA. Agreement between replicate measurements for AQURO was 6, 5 and 7mm(2)for automated analysis of the three pairs of datasets. CONCLUSIONS: By eliminating the need to identify the orifice location, AQURO avoids an important source of measurement variability. Compared with PISA, it also reduces the analysis time allowing analysis and averaging of data from significantly more beats, improving the consistency of EROA quantification. AQURO, being fully automated, is a simple, effective enhancement for EROA quantification using standard echocardiographic equipment.

Evidence-based recommendations for PISA measurements in mitral regurgitation: systematic review, clinical and in-vitro study.

BACKGROUND: Guidelines for quantifying mitral regurgitation (MR) using "proximal isovelocity surface area" (PISA) instruct operators to measure the PISA radius from valve orifice to Doppler flow convergence "hemisphere". Using clinical data and a physically-constructed MR model we (A) analyse the actually-observed colour Doppler PISA shape and (B) test whether instructions to measure a "hemisphere" are helpful. METHODS AND RESULTS: In part A, the true shape of PISA shells was investigated using three separate approaches. First, a systematic review of published examples consistently showed non-hemispherical, "urchinoid" shapes. Second, our clinical data confirmed that the Doppler-visualized surface is non-hemispherical. Third, in-vitro experiments showed that round orifices never produce a colour Doppler hemisphere. In part B, six observers were instructed to measure hemisphere radius rh and (on a second viewing) urchinoid distance (du) in 11 clinical PISA datasets; 6 established experts also measured PISA distance as the gold standard. rh measurements, generated using the hemisphere instruction significantly underestimated expert values (-28%, p<0.0005), meaning r(h)(2) was underestimated by approximately 2-fold. du measurements, generated using the non-hemisphere instruction were less biased (+7%, p=0.03). Finally, frame-to-frame variability in PISA distance was found to have a coefficient of variation (CV) of 25% in patients and 9% in in-vitro data. Beat-to-beat variability had a CV of 15% in patients. CONCLUSIONS: Doppler-visualized PISA shells are not hemispherical: we should avoid advising observers to measure a hemispherical radius because it encourages underestimation of orifice area by approximately two-fold. If precision is needed (e.g. to detect changes reliably) multi-frame averaging is essential.

Carotid artery hemodynamics: observing patient-specific changes with amlodipine and lisinopril by using MR imaging computation fluid dynamics.

PURPOSE: To assess whether using magnetic resonance (MR) imaging combined with computational fluid dynamics (CFD) could reveal changes in common carotid artery (CCA) flow and wall shear stress (WSS) that might contribute to differences in CCA remodeling between amlodipine, a calcium channel blocker, and lisinopril, an angiotensin-converting enzyme inhibitor, despite similar reductions in blood pressure (BP). MATERIALS AND METHODS: Institutional review board approval was obtained, and participants gave informed consent. Nine subjects with hypertension were recruited into a double-blind placebo-controlled randomized three-way crossover study to compare the hemodynamic effects of 7 days of treatment with placebo, amlodipine, or lisinopril. After each treatment period, patients underwent CCA ultrasonography, BP measurement, and MR imaging with CFD. Analyses were performed by using repeated-measures analysis of variance, followed by the Tukey test or the Wilcoxon matched-pairs test. RESULTS: Amlodipine and lisinopril lowered BP similarly, but CCA flow rate was significantly higher (P < .01) and distal vascular resistance was lower (P = .016) after amlodipine treatment than after lisinopril treatment. WSS on the inner wall of the CCA was significantly lower after lisinopril treatment than after amlodipine treatment (P = .03). The change in WSS in the CCA correlated with the change in vascular resistance (r = -0.85, P < .001). CONCLUSION: Amlodipine causes increased blood flow and increased time-averaged WSS in the CCA compared with lisinopril, despite similar reductions in BP. Differences in the subacute hemodynamic effects of amlodipine and lisinopril could contribute to the differences in CCA remodeling seen in long-term studies. SUPPLEMENTAL MATERIAL: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.10100788/-/DC1.

Low wall shear stress predicts subsequent development of wall hypertrophy in lower limb bypass grafts.

BACKGROUND: Venous grafts commonly develop myointimal hyperplasia, which can lead to stenoses and, ultimately, with expression of adhesion molecules, lumenal occlusion. The aim of the present study was to investigate whether wall shear stress measured post-operatively would predict subsequent myointimal hypertrophy in lower limb venous bypass grafts. METHODS: Magnetic resonance imaging and ultrasound were performed in a cohort of patients following lower limb venous bypass graft surgery for peripheral arterial disease at baseline (1-2 weeks) and at follow-up (9-12 months). Wall shear stress was determined at baseline using computational fluid dynamics techniques and intima-media thickness along the length of the graft was measured by ultrasound at baseline and follow up. RESULTS: Complete follow-up was possible in eight patients, in whom low wall shear stress at baseline predicted high intima-media thickness. The relationship between wall shear stress (WSS) and intima-media thickness (IMT) was curvilinear with IMT increasing sharply at lower levels of WSS (IMT >1.0 mm at <0.3 Pa). CONCLUSIONS: Low wall shear stress is associated with subsequent increase in myointimal thickness in lower limb venous bypass grafts. This is believed to be the first prospective study in humans to demonstrate the relationship between low wall shear stress and myointimal thickening and indicates a likely causative role for low wall shear stress in the development of myointimal hyperplasia.

Expression of a fused fpg gene in E. coli and engineering a strain Comamonas testosteroni ZD4-1-fpg for environmental application.

A fused fpg gene composed of phe B and gfp gene, which encoded catechol 2,3-dioxygenase (C23O) and green fluorescence protein (GFP), respectively, was expressed in E. coli to investigate its functional intactness. The expression results showed that C23O activity was detected in the induced bacterial cells and the E. coli cells containing the fusion protein emitted green fluorescence under epifluorescence microscopy, indicating that the fused fpg gene expressed correctly in E. coli. After expressed in E. coli, the fpg gene was transferred into the chromosome of a wild-type strain Comamonas testosteroni ZD4-1 by a pUT mini-Tn5 type vector pUT-Hg-fpg. The constructed genetically engineered bacterium strain C. testosteroni ZD4-1-fpg was also able to emit green fluorescence under epifluorescence microscopy. The stability assay showed that fpg gene could be detected in the host strain after 10 times of transfer inoculation, indicating the fpg gene is very stable. These results revealed that the Comamona testosteroni ZD4-1-fpg maybe used as not only an aromatic compound-biodegrading strain but also as an indicator strain to monitor the fate of the bacterial strains in the bioremediation.