Christopher J. Elkins

Flow effects in balanced steady state free precession imaging

An analysis of the effect of flow on 2D fully balanced steady state free precession (SSFP) imaging is presented. Transient and steady‐state SSFP signal intensities in the presence of steady and pulsatile flow were simulated using a matrix formalism based on the Bloch equations. Various through‐plane flow waveforms and rates were modeled numerically considering factors such as the excitation slice profile and both in‐ and out‐flow effects. Phantom measurements in an experimental setup that allowed the assessment of SSFP signal properties as a function of frequency offset and flow rate demonstrated that the computer simulations provided a suitable description of the effects of flow in SSFP imaging. A volunteer scan was performed to provide in vivo validations. For accurate modeling of SSFP signal intensities it is crucial to include effects such as imperfect slice profiles and, more importantly, “out‐of‐slice” contributions to the signal. Both simulations and experiments show that there can be considerably large—frequency offset dependent—signal contributions from flowing spins that have already left the imaging slice but still add to the SSFP signal. Although spins leaving the slice do not experience additional RF‐excitation, gradient activity is not confined to the region of excitations and the balanced nature of the SSFP imaging gradients allows “out‐of‐slice” transverse magnetization to contribute to the total SSFP signal, effectively by broadening the slice thickness for flowing spins. This results in a frequency dependence of in‐flow related signal enhancement and flow artifacts. Magn Reson Med 50:892–903, 2003.

Generalized reconstruction of phase contrast MRI: Analysis and correction of the effect of gradient field distortions†

To characterize gradient field nonuniformity and its effect on velocity encoding in phase contrast (PC) MRI, a generalized model that describes this phenomenon and enables the accurate reconstruction of velocities is presented. In addition to considerable geometric distortions, inhomogeneous gradient fields can introduce deviations from the nominal gradient strength and orientation, and therefore spatially‐dependent first gradient moments. Resulting errors in the measured phase shifts used for velocity encoding can therefore cause significant deviations in velocity quantification. The true magnitude and direction of the underlying velocities can be recovered from the phase difference images by a generalized PC velocity reconstruction, which requires the acquisition of full three‐directional velocity information. The generalized reconstruction of velocities is applied using a matrix formalism that includes relative gradient field deviations derived from a theoretical model of local gradient field nonuniformity. In addition, an approximate solution for the correction of one‐directional velocity encoding is given. Depending on the spatial location of the velocity measurements, errors in velocity magnitude can be as high as 60%, while errors in the velocity encoding direction can be up to 45°. Results of phantom measurements demonstrate that effects of gradient field nonuniformity on PC‐MRI can be corrected with the proposed method. Magn Reson Med 50:791–801, 2003. Published 2003 Wiley‐Liss, Inc.

Comparison of CFD and MRI flow and velocities in an in vitro large artery bypass graft model.

Bypass graft failures have been attributed to various hemodynamic factors, including flow stasis and low shear stress. Ideally, surgeries would minimize the occurrence of these detrimental flow conditions, but surgeons cannot currently assess this. Numerical simulation techniques have been proposed as one method for predicting changes in flow distributions and patterns from surgical bypass procedures, but comparisons against experimental results are needed to assess their usefulness. Previous in vitro studies compared simulated results against experimentally obtained measurements, but they focused on peripheral arteries, which have lower Reynolds numbers than those found in the larger arteries. In this study, we compared simulation results against measurements obtained using magnetic resonance imaging (MRI) techniques for a phantom model of a stenotic vessel with a bypass graft under conditions suitable for surgical planning purposes and with inlet Reynolds numbers closer to those found in the larger arteries. Comparisons of flow rate and velocity profiles were performed at maximum and minimum flows at four locations and used simulation results that were temporally and spatially averaged, key postprocessing when comparing against phase contrast MRI measurements. The maximum error in the computed volumetric flow rates was 6% of the measured values, and excellent qualitative agreement was obtained for the through-plane velocity profiles in both magnitude and shape. The in-plane velocities also agreed reasonably well at most locations.

High-Efficiency Endovascular Gene Delivery Via Therapeutic Ultrasound

OBJECTIVES We studied enhancement of local gene delivery to the arterial wall by using an endovascular catheter ultrasound (US). BACKGROUND Ultrasound exposure is standard for enhancement of in vitro gene delivery. We postulate that in vivo endovascular applications can be safely developed. METHODS We used a rabbit model of arterial mechanical overdilation injury. After arterial overdilation, US catheters were introduced in bilateral rabbit femoral arteries and perfused with plasmidor adenovirus-expressing blue fluorescent protein (BFP) or phosphate buffered saline. One side received endovascular US (2 MHz, 50 W/cm2, 16 min), and the contralateral artery did not. RESULTS Relative to controls, US exposure enhanced BFP expression measured via fluorescence 12-fold for plasmid (1,502.1+/-927.3 vs. 18,053.9+/-11,612 microm2, p < 0.05) and 19-fold for adenovirus (877.1+/-577.7 vs. 17,213.15+/-3,892 microm2, p < 0.05) while increasing cell death for the adenovirus group only (26+/-5.78% vs. 13+/-2.55%, p < 0.012). CONCLUSIONS Endovascular US enhanced vascular gene delivery and increased the efficiency of nonviral platforms to levels previously attained only by adenoviral strategies.

Extracranial Venous Drainage Patterns in Patients with Multiple Sclerosis and Healthy Controls

BACKGROUND AND PURPOSE: CCSVI hypothesizes an association between impaired extracranial venous drainage and MS. Published sonographic criteria for CCSVI are controversial, and no MR imaging data exist to support the CCSVI hypothesis. Our purpose was to evaluate possible differences in the extracranial venous drainage of MS and healthy controls using both TOF and contrast-enhanced TRICKS MRV. MATERIALS AND METHODS: Healthy subjects (n = 20) and patients with MS (n = 19) underwent axial 2D-TOF neck MRV (to assess flattening) and TRICKS MRV (to assess collaterals) at 3T. Two neuroradiologists blinded to cohort status scored IJV flattening and the severity of non-IJV collaterals by using a 4-point qualitative scale (normal = 0, mild = 1, moderate = 2, severe = 3). κ was used to assess reader agreement. Comparisons between groups were performed by using the Wilcoxon rank sum test. The Spearman rank correlation was used to assess the relationship between IJV flattening and collateral scores and, in patients with MS, EDSS scores. RESULTS: The 2 groups were matched for age and sex (MS, 45 ± 8 years, 79% female; healthy controls, 47 ± 10 years, 65% female). Reader agreement for IJV flattening and collateral severity was good (κ = 0.74) and moderate (κ = 0.58), respectively. While IJV flattening was seen in both patients with MS and healthy controls, scores for the patients with MS were significantly higher (P = .002). Despite a trend, there was no significant difference in collateral scores between groups (P = .063). There was a significant positive correlation between flattening and collateral scores (ρ = 0.32, P = .005) and EDSS and flattening scores (ρ = 0.45, P = .004) but not between EDSS and collateral scores (ρ = 0.01, P = .97). CONCLUSIONS: These results indicate that patients with MS have greater IJV flattening and a trend toward more non-IJV collaterals than healthy subjects. The role that this finding plays in the pathogenesis or progression of MS, if any, requires further study.

Turbulent heat and momentum transport on a rotating disk

Measurements in the turbulent momentum and thermal boundary layers on a rotating disk with a uniform heat flux surface are described for Reynolds numbers up to 10 6 . Measurements include mean velocities and temperatures, all six Reynolds stresses, turbulent temperature fluctuations, and three turbulent heat fluxes. The mean velocity profiles have no wake region, but the mean temperature profiles do. The turbulent temperature fluctuations have a large peak in the outer layer, and there is a third turbulent heat flux in the cross-flow direction. Correlation coefficients and structure parameters are not constant across the boundary layer as they are in two-dimensional boundary layers (2DBLs), and their values are lower. The turbulent Prandtl number agrees with 2DBL values in the lower part of the outer region but is reduced from the 2DBL values higher in the boundary layer. In the outer region of the boundary layer, the transport processes differ significantly from what is observed in two-dimensional turbulent boundary layers: ejections dominate the transport of momentum while both ejections and sweeps contribute to the transport of the passive scalar

In vivo vascular engineering of vein grafts: Directed migration of smooth muscle cells by perivascular release of elastase limits neointimal proliferation

PURPOSE Saphenous vein bypass grafting for coronary revascularization procedures remains limited by accelerated neointima formation. It was hypothesized that creation of a modified chemotactic gradient in vivo could guide migration of smooth muscle cells (SMCs) peripherally instead of in a luminal direction and reduce intimal hyperplasia during vein graft arterialization. MATERIALS AND METHODS Surgical bypass vein grafting to femoral arteries was performed in adult male New Zealand White rabbits (n = 8 per treatment group; five for 7 d and three for 28 d). Controlled-release microspheres delivering elastase or buffered polymer only were administered perivascularly at the vein graft site. At 7 days, five vein grafts per group were harvested and cross-sections were immunostained with anti-proliferating cell nuclear antigen (PCNA) to determine the number and distribution of proliferating SMCs. At 28 days, three vein grafts per group were harvested and intima-to-media (I/M) ratios were calculated after staining with Verhoeff von Gieson-Masson trichrome stain. RESULTS Significant early outward-directed elastin degradation resulted from elastase treatment. Concurrently, proliferating SMCs migrated peripherally. PCNA(+) cells in the outer half of the wall increased 2.37 fold compared to procedural controls (P <.0001). Directional shifts in SMC migration underlie these results because overall SMC proliferation was not significantly different. At 28 days after vein graft surgery, a 38% reduction (P =.0008) in neointima was observed relative to procedural controls. CONCLUSION Directional guidance of SMC responses through perivascular elastase release achieves favorable vein graft remodeling characteristics, including limited neointima development. This represents practical evidence that SMC migration can be directionally guided in vivo in a vein graft model and that plaque progression can be prevented by redistributing elastin without decreasing functional vein graft wall stability.

Stent-based Controlled Release of Intravascular Angiostatin to Limit Plaque Progression and In-Stent Restenosis

PURPOSE To evaluate the importance of angiogenesis in plaque progression after stent placement, this study examines stent-based controlled delivery of the antiangiogenic agent, angiostatin, in a rabbit model. MATERIALS AND METHODS Controlled release biodegradable microspheres delivering angiostatin or polymer-only microspheres (polylactic-co-glycolic-acid-polyethylene glycol; PLGA/PEG) were loaded in channeled stents, anchored, and deployed in the aorta of adult New Zealand white rabbits (n = 6 animals per group, three each per time point). The stented aortas were harvested at 7 days and 28 days and evaluated for neovascularization, local inflammation, vascular smooth muscle cell proliferation, and in-stent plaque progression. RESULTS At 7 days, neovascularization was significantly decreased in the angiostatin groups (1.6 +/- 1.6 neovessels per mm(2) plaque) versus the control group (15.4 +/- 2.6 neovessels per mm(2) plaque; P =.00081), as were local inflammation where angiostatin-treated groups demonstrated significantly lower macrophage recruitment per cross section (34.9 +/- 4.9 cells per cross section) relative to the control group (55.2 +/- 3.84 cells per cross section; P =.0037). And a significant decrease in the overall vascular smooth muscle cell proliferation (143.8 +/- 26.3 Ki-67 positive cells per mm(2)) relative to the control group (263.2 +/- 16.6 Ki-67 positive cells per mm(2); P =.00074). At both 7 and 28 days, in-stent plaque progression in the angiostatin groups was successfully limited relative to the control group by 54% (0.255 +/- 0.019% of cross section; P =.00016) and 19% (1.981 +/- 0.080; P =.0033) respectively and resulted in reduction of in-stent restenosis relative to the control group. CONCLUSION Angiostatin-eluting stents may limit neovascularity after arterial implantation, offer insight into in-stent restenosis, and allow future refinement of bioactive stent designs and clinical strategies, particularly in light of evidence that intimal smooth muscle cells may in part be marrow-derived.

Inverse Design of and Experimental Measurements in a Double-Passage Transonic Turbine Cascade Model

A new transonic turbine cascade model that accurately produces infinite cascade flow conditions with minimal compressor requirements is presented. An inverse design procedure using the Favre-averaged Navier-Stokes equations and k- turbulence model based on the method of steepest descent was applied to a geometry consisting of a single turbine blade in a passage. For a fixed blade geometry, the passage walls were designed such that the surface isentropic Mach number (SIMN) distribution on the blade in the passage matched the SIMN distribution on the blade in an infinite cascade, while maintaining attached flow along both passage walls. An experimental rig was built that produces realistic flow conditions, and also provides the extensive optical access needed to obtain detailed particle image velocimetry measurements around the blade. Excellent agreement was achieved between computational fluid dynamics (CFD) of the infinite cascade SIMN, CFD of the designed double passage SIMN, and the measured SIMN. DOI: 10.1115/1.1929810

Full-Field Flow Measurements and Heat Transfer of a Compact Jet Impingement Array With Local Extraction of Spent Fluid

Jet impingement cooling is widely used due to the very high heat transfer coefficients that are attainable. Both single and multiple jet systems can be used, however, multiple jet systems offer higher and more uniform heat transfer. A staggered array of 8.46 mm diameter impingement jets with jet-to-jet spacing of 2.34 D was examined where the spent fluid is extracted through one of six 7.36 mm diameter extraction holes regularly located around each jet. The array had an extraction area ratio (A e /A jet ) of 2.23 locally and was tested with a jet-to-target spacing (H/D) of 1.18 jet diameters. Magnetic resonance velocimetry was used to both quantify and visualize the three dimensional flow field inside the cooling cavity at jet Reynolds numbers of 2600 and 5300. The spatially averaged velocity measurements showed a smooth transition is possible from the impingement jet to the extraction hole without the presence of large vortical structures. Mean Nusselt number measurements were made over a jet Reynolds number range of 2000―10,000. Nusselt numbers near 75 were measured at the highest Reynolds number with an estimated uncertainty of 7%. Large mass flow rate per unit heat transfer area ratios were required because of the small jet-to-jet spacing.