Investigation of Aortic Wall Thickness, Stiffness and Flow Reversal in Patients With Cryptogenic Stroke: A 4D Flow MRI Study.

BACKGROUND: Stroke etiology is undetermined in approximately one-sixth to one-third of patients. The presence of aortic flow reversal and plaques in the descending aorta (DAo) has been identified as a potential retrograde embolic mechanism. PURPOSE: To assess the relationships between aortic stiffness, wall thickness, and flow reversal in patients with cryptogenic stroke and healthy controls. STUDY TYPE: Prospective. POPULATION: Twenty one patients with cryptogenic stroke and proven DAo plaques (69 ± 9 years, 43% female), 18 age-matched controls (age: 65 ± 8 years, 61% female), and 14 younger controls (36 ± 9 years, 57% female). FIELD STRENGTH/SEQUENCE: 1.5T; 4D flow MRI and 3D dark blood T1 -weighted turbo spin echo MRI of the aorta. ASSESSMENT: Noncontrast aortic 4D flow MRI to measure 3D flow dynamics and 3D dark blood aortic wall MRI to assess wall thickness. 4D flow MRI analysis included automated quantification of aortic stiffness by pulse wave velocity (PWV) and voxelwise mapping of the flow reversal fraction (FRF). STATISTICAL TESTS: Analysis of variance (ANOVA) or Kruskal-Wallis tests, Student's unpaired t-tests or Wilcoxon rank-sum tests, regression analysis. RESULTS: Aortic PWV and FRF were statistically higher in patients (8.9 ± 1.7 m/s, 18.4 ± 7.7%) than younger controls (5.3 ± 0.8 m/s, P < 0.0167; 8.5 ± 2.9%, P < 0.0167), but not age-matched controls (8.2 ± 1.6 m/s, P = 0.22; 15.6 ± 5.8%, P = 0.22). Maximum aortic wall thickness was higher in patients (3.1 ± 0.7 mm) than younger controls (2.2 ± 0.2 mm, P < 0.0167) and age-matched controls (2.7 ± 0.5 mm) (P < 0.0167). For all subjects, positive relationships were found between PWV and age (R2 = 0.71, P < 0.05), aortic wall thickness (R2 = 0.20, P < 0.05), and FRF (R2 = 0.47, P < 0.05). Patients demonstrated relationships between PWV and FRF in the ascending aorta (R2 = 0.32, P < 0.05) and arch (R2 = 0.24, P < 0.05). DATA CONCLUSION: This study showed the utility of 4D flow MRI for evaluating aortic PWV and voxelwise flow reversal. Positive relationships between aortic PWV, wall thickness, and flow reversal support the hypothesis that aortic stiffness is involved in this retrograde embolic mechanism. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 1.

Renin Angiotensin System Inhibitors Reduce Aortic Stiffness and Flow Reversal After a Cryptogenic Stroke.

BACKGROUND: Blood flow reversal is a possible mechanism for retrograde embolism in the setting of high-risk atherosclerotic plaques in the descending aorta (DAo). Evidence suggests that pulse wave velocity (PWV) is a determinant of blood flow reversal and can be reduced by the destiffening effect of renin-angiotensin system inhibitors (RASI). PURPOSE: To evaluate the impact of antihypertensive therapy on in vivo changes in PWV and flow reversal in patients with cryptogenic stroke. STUDY TYPE: Prospective. POPULATION: Sixteen patients (69 ± 9 years; 10 males) included after cryptogenic stroke. FIELD STRENGTH/SEQUENCE: 3T. 4D flow sequence (temporal resolution = 19.6 msec) ASSESSMENT: Patients underwent aortic MRI at baseline and at 6-month follow-up. Patients received standard-of-care antihypertensive therapy that were classified as RASI vs. non-RASI medications (ie, destiffening vs. nondestiffening).We compared aortic PWV, flow reversal fraction (FRF), aortic measurements, cardiac function, and other aortic and cardiac measurements in the antihypertensive therapy groups. STATISTICAL TESTS: Two-tailed paired or unpaired Student's t-tests (normal distributions) or Wilcoxon tests (nonnormal distribution). Univariate correlations using Pearson correlation coefficients. RESULTS: There was a significant decrease in PWV in the RASI (n = 10) group (9.4 ± 1.6 m/s vs. 8.3 ± 1.9 m/s; P < 0.05), as well as FRF (18.6% ± 4.1% vs. 16.3% ± 4.0%; P < 0.05) between baseline and the 6-month MRI studies. There were no changes in PWV or FRF in the non-RASI (n = 6) group (P = 0.146 and P = 0.32). A decrease in FRF was significantly correlated with a decrease in PWV (r = 0.53; P < 0.05). DATA CONCLUSION: The findings of our study suggest that RASI therapy after cryptogenic stroke resulted in a decrease of blood flow reversal and aortic stiffness. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY STAGE: 4.

Development of a rotation phantom for phase contrast MRI sequence validation and quality control.

PURPOSE: To develop a reliable, consistent, and reproducible reference phantom for error quantification of phase-contrast MRI so it can be used for validation and quality control. METHODS: An air-driven rotation phantom consisting of a steadily rotating cylinder surrounded by a static ring both filled with agarose gel was developed. Rotational speed was measured and controlled in real time using an optical counter and a closed-loop controller. Consistency of the phantom was assessed by recording variations in rotational speed. The phantom was imaged with 2D phase-contrast MRI, and the velocity at each point was compared with analytically predicted velocity. Additionally, to examine reproducibility, the phantom was run with the same rotational speed on 2 different days and imaged using the same phase-contrast MRI protocol. RESULTS: The rotation phantom provided consistent rotational speed with 2 revolutions per minute SD from the set value for 20 min. Comparison between predicted and measured velocities demonstrated excellent agreement (intraclass correlation coefficient of 0.99). The RMS error in velocity components were less than 1% of maximum value. The scan-rescan experiment showed that the phantom can reproduce the same velocity distributions (intraclass correlation coefficient of 0.99) using the same rotational speed and MRI settings. CONCLUSION: The developed rotation phantom provided well-defined and reproducible linear velocity distributions, which can be used for systematic and quantitative error analysis of phase-contrast MRI for a range of known velocities.

Bilateral Multiband 4D Flow MRI of the Carotid Arteries at 7T.

PURPOSE: Simultaneous multislab (SMSb) 4D flow MRI was developed and implemented at 7T for accelerated acquisition of the 3D blood velocity vector field in both carotid bifurcations. METHODS: SMSb was applied to 4D flow to acquire blood velocities in both carotid bifurcations in sagittal orientation using a local transmit/receive coil at 7T. B1+ transmit efficiency was optimized by B1+ shimming. SMSb 4D flow was obtained in 8 healthy subjects in single-band (SB) and multiband (MB) fashion. Additionally, MB data were retrospectively undersampled to simulate GRAPPA R = 2 (MB2_GRAPPA2), and both SB datasets were added to form an artificial MB dataset (SumSB). The band separation performance was quantified by signal leakage. Peak velocity and total flow values were calculated and compared to SB via intraclass correlation analysis (ICC). RESULTS: Clean slab separation was achieved yielding a mean signal leakage of 13% above the mean SB noise level. Mean total flow for MB2, SumSB, and MB_GRAPPA2 deviated less than 9% from the SB values. Peak velocities averaged over all vessels and subjects were 0.48 ± 0.11 m/s for SB, 0.47 ± 0.12 m/s for SumSB, 0.50 ± 0.13 m/s for MB2, and 0.53 ± 0.13 m/s for MB2_GRAPPA2. ICC revealed excellent absolute agreement and consistency of total flow for all methods compared to SB2. Peak velocity showed good to excellent agreement and consistency for SumSB and MB2 and MB2_GRAPPA2 method showed poor to excellent agreement and good to excellent consistency. CONCLUSION: Simultaneous multislab 4D Flow MRI allows accurate quantification of total flow and peak velocity while reducing scan times.

Efficient triple-VENC phase-contrast MRI for improved velocity dynamic range.

PURPOSE: To evaluate the utility of an efficient triple velocity-encoding (VENC) 4D flow MRI implementation to improve velocity unwrapping of 4D flow MRI data with the same scan time as an interleaved dual-VENC acquisition. METHODS: A balanced 7-point acquisition was used to derive 3 sets of 4D flow images corresponding to 3 different VENCs. These 3 datasets were then used to unwrap the aliased lowest VENC into a minimally aliased, triple-VENC dataset. Triple-VENC MRI was evaluated and compared with dual-VENC MRI over 3 different VENC ranges (50-150, 60-150, and 60-180 cm/s) in vitro in a steadily rotating phantom as well as in a pulsatile flow phantom. In vivo, triple-VENC data of the thoracic aorta were also evaluated in 3 healthy volunteers (2 males, 26-44 years old) with VENC = 50/75/150 cm/s. Two triple-VENC (triconditional and biconditional) and 1 dual-VENC unwrapping algorithms were quantitatively assessed through comparison to a reference, unaliased, single-VENC scan. RESULTS: Triple-VENC 4D flow constant rotation phantom results showed high correlation with the analytical solution (intraclass correlation coefficient = 0.984-0.995, P < .001) and up to a 61% reduction in velocity noise compared with the corresponding single-VENC scans (VENC = 150, 180 cm/s). Pulsatile flow phantom experiments demonstrated good agreement between triple-VENC and single-VENC acquisitions (peak flow < 0.8% difference; peak velocity < 11.7% difference). Triconditional triple-VENC unwrapping consistently outperformed dual-VENC unwrapping, correctly unwrapping more than 83% and 46%-66% more voxels in vitro and in vivo, respectively. CONCLUSION: Triple-VENC 4D flow MRI adds no additional scan time to dual-VENC MRI and has the potential for improved unwrapping to extend the velocity dynamic range beyond dual-VENC methods.

Parametric Hemodynamic 4D Flow MRI Maps for the Characterization of Chronic Thoracic Descending Aortic Dissection.

BACKGROUND: Systematic evaluation of complex flow in the true lumen and false lumen (TL, FL) is needed to better understand which patients with chronic descending aortic dissection (DAD) are predisposed to complications. PURPOSE: To develop quantitative hemodynamic maps from 4D flow MRI for evaluating TL and FL flow characteristics. STUDY TYPE: Retrospective. POPULATION: In all, 20 DAD patients (age = 60 ± 11 years; 12 male) (six medically managed type B AD [TBAD], 14 repaired type A AD [rTAAD] now with ascending aortic graft [AAo] or elephant trunk [ET1] repair) and 21 age-matched controls (age = 59 ± 10 years; 13 male) were included. FIELD STRENGTH/SEQUENCE: 1.5T, 3T, 4D flow MRI. ASSESSMENT: 4D flow MRI was acquired in all subjects. Data analysis included 3D segmentation of TL and FL and voxelwise calculation of forward flow, reverse flow, flow stasis, and kinetic energy as quantitative hemodynamics maps. STATISTICAL TESTS: Analysis of variance (ANOVA) or Kruskal-Wallis tests were performed for comparing subject groups. Correlation and Bland-Altman analysis was performed for the interobserver study. RESULTS: Patients with rTAAD presented with elevated TL reverse flow (AAo repair: P = 0.004, ET1: P = 0.018) and increased TL kinetic energy (AAo repair: P = 0.0002, ET1: P = 0.011) compared to controls. In addition, TL kinetic energy was increased vs. patients with TBAD (AAo repair: P = 0.021, ET1: P = 0.048). rTAAD was associated with higher FL kinetic energy and lower FL stasis compared to patients with TBAD (AAo repair: P = 0.002, ET1: P = 0.024 and AAo repair: P = 0.003, ET1: P = 0.048, respectively). DATA CONCLUSION: Quantitative maps from 4D flow MRI demonstrated global and regional hemodynamic differences between DAD patients and controls. Patients with rTAAD vs. TBAD had significantly altered regional TL and FL hemodynamics. These findings indicate the potential of 4D flow MRI-derived hemodynamic maps to help better evaluate patients with DAD. LEVEL OF EVIDENCE: 3 Technical Efficacy Stage: 1 J. Magn. Reson. Imaging 2020;51:1357-1368.

Standardized Evaluation of Cerebral Arteriovenous Malformations Using Flow Distribution Network Graphs and Dual-venc 4D Flow MRI.

BACKGROUND: Cerebral arteriovenous malformations (AVMs) are pathological connections between arteries and veins. Dual-venc 4D flow MRI, an extended 4D flow MRI method with improved velocity dynamic range, provides time-resolved 3D cerebral hemodynamics. PURPOSE: To optimize dual-venc 4D flow imaging parameters for AVM; to assess the relationship between spatial resolution, acceleration, and flow quantification accuracy; and to introduce and apply the flow distribution network graph (FDNG) paradigm for storing and analyzing complex neurovascular 4D flow data. STUDY TYPE: Retrospective cohort study. SUBJECTS/PHANTOM: Scans were performed in a specialized flow phantom: 26 healthy subjects (age 41 ± 17 years) and five AVM patients (age 27-68 years). FIELD STRENGTH/SEQUENCE: Dual-venc 4D flow with varying spatial resolution and acceleration factors were performed at 3T field strength. ASSESSMENT: Quantification accuracy was assessed in vitro by direct comparison to measured flow. FDNGs were used to quantify and compare flow, peak velocity (PV), and pulsatility index (PI) between healthy controls with various Circle of Willis (CoW) anatomy and AVM patients. STATISTICAL TESTS: In vitro measurements were compared to ground truth with Student's t-test. In vivo groups were compared with Wilcoxon rank-sum test and Kruskal-Wallis test. RESULTS: Flow was overestimated in all in vitro experiments, by an average 7.1 ± 1.4% for all measurement conditions. Error in flow measurement was significantly correlated with number of voxels across the channel (P = 3.11 × 10-28 ) but not with acceleration factor (P = 0.74). For the venous-arterial PV and PI ratios, a significant difference was found between AVM nidal and extranidal circulation (P = 0.008 and 0.05, respectively), and between AVM nidal and healthy control circulation (P = 0.005 and 0.003, respectively). DATA CONCLUSION: Dual-venc 4D flow MRI and standardized FDNG analysis might be feasible in clinical applications. Venous-arterial ratios of PV and PI are proposed as network-based biomarkers characterizing AVM nidal hemodynamics. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;50:1718-1730.

Reconfigurable MRI technology for low-SAR imaging of deep brain stimulation at 3T: Application in bilateral leads, fully-implanted systems, and surgically modified lead trajectories.

Patients with deep brain stimulation devices highly benefit from postoperative MRI exams, however MRI is not readily accessible to these patients due to safety risks associated with RF heating of the implants. Recently we introduced a patient-adjustable reconfigurable coil technology that substantially reduced local SAR at tips of single isolated DBS leads during MRI at 1.5 T in 9 realistic patient models. This contribution extends our work to higher fields by demonstrating the feasibility of scaling the technology to 3T and assessing its performance in patients with bilateral leads as well as fully implanted systems. We developed patient-derived models of bilateral DBS leads and fully implanted DBS systems from postoperative CT images of 13 patients and performed finite element simulations to calculate SAR amplification at electrode contacts during MRI with a reconfigurable rotating coil at 3T. Compared to a conventional quadrature body coil, the reconfigurable coil system reduced the SAR on average by 83% for unilateral leads and by 59% for bilateral leads. A simple surgical modification in trajectory of implanted leads was demonstrated to increase the SAR reduction efficiency of the rotating coil to >90% in a patient with a fully implanted bilateral DBS system. Thermal analysis of temperature-rise around electrode contacts during typical brain exams showed a 15-fold heating reduction using the rotating coil, generating <1°C temperature rise during ∼4-min imaging with high-SAR sequences where a conventional CP coil generated >10°C temperature rise in the tissue for the same flip angle.

Semi-automated analysis of 4D flow MRI to assess the hemodynamic impact of intracranial atherosclerotic disease.

PURPOSE: This study evaluated the feasibility of using 4D flow MRI and a semi-automated analysis tool to assess the hemodynamic impact of intracranial atherosclerotic disease (ICAD). The ICAD impact was investigated by evaluating pressure drop (PD) at the atherosclerotic stenosis and changes in cerebral blood flow distribution in patients compared to healthy controls. METHODS: Dual-venc 4D flow MRI was acquired in 25 healthy volunteers and 16 ICAD patients (ICA, N = 3; MCA, N = 13) with mild (<50%), moderate (50-69%), or severe (>70%) intracranial stenosis. A semi-automated analysis tool was developed to quantify velocity and flow from 4D flow MRI and to evaluate cerebral blood flow redistribution. PD at stenosis was estimated using the Bernoulli equation. The PD calculation was examined by an in vitro phantom study against flow simulations. RESULTS: Flow analysis in controls indicated symmetry in blood flow rate (FR) and peak velocity (PV) between the brain hemispheres. For patients, PV in the affected hemisphere was significantly (65%) higher than the normal side (P = 0.002). However, FR to both hemispheres of the brain was the same. The PD depicted significant correlation with PV asymmetry in patients (ρ = 0.67 and P = 0.02), and it was significantly higher for severe compared to moderate stenosis (3.73 vs. 2.30 mm Hg, P = 0.02). CONCLUSION: 4D flow MRI quantification enables assessment of the hemodynamic impact of ICAD. The significant difference of the PD between patients with severe and moderate stenosis and its correlation with PV asymmetry suggest that PD may be a pertinent hemodynamic biomarker to evaluate ICAD.

Aortic 4D flow MRI in 2 minutes using compressed sensing, respiratory controlled adaptive k-space reordering, and inline reconstruction.

PURPOSE: To evaluate the accuracy and feasibility of a free-breathing 4D flow technique using compressed sensing (CS), where 4D flow imaging of the thoracic aorta is performed in 2 min with inline image reconstruction on the MRI scanner in less than 5 min. METHODS: The 10 in vitro 4D flow MRI scans were performed with different acceleration rates on a pulsatile flow phantom (9 CS acceleration factors [R = 5.4-14.1], 1 generalized autocalibrating partially parallel acquisition [GRAPPA] R = 2). Based on in vitro results, CS-accelerated 4D flow of the thoracic aorta was acquired in 20 healthy volunteers (38.3 ± 15.2 years old) and 11 patients with aortic disease (61.3 ± 15.1 years) with R = 7.7. A conventional 4D flow scan was acquired with matched spatial coverage and temporal resolution. RESULTS: CS depicted similar hemodynamics to conventional 4D flow in vitro, and in vivo, with >70% reduction in scan time (volunteers: 1:52 ± 0:25 versus 7:25 ± 2:35 min). Net flow values were within 3.5% in healthy volunteers, and voxel-by-voxel comparison demonstrated good agreement. CS significantly underestimated peak velocities (vmax ) and peak flow (Qmax ) in both volunteers and patients (volunteers: vmax , -16.2% to -9.4%, Qmax : -11.6% to -2.9%, patients: vmax , -11.2% to -4.0%; Qmax , -10.2% to -5.8%). CONCLUSION: Aortic 4D flow with CS is feasible in a two minute scan with less than 5 min for inline reconstruction. While net flow agreement was excellent, CS with R = 7.7 produced underestimation of Qmax and vmax ; however, these were generally within 13% of conventional 4D flow-derived values. This approach allows 4D flow to be feasible in clinical practice for comprehensive assessment of hemodynamics.

Merging computational fluid dynamics and 4D Flow MRI using proper orthogonal decomposition and ridge regression.

Time resolved phase-contrast magnetic resonance imaging 4D-PCMR (also called 4D Flow MRI) data while capable of non-invasively measuring blood velocities, can be affected by acquisition noise, flow artifacts, and resolution limits. In this paper, we present a novel method for merging 4D Flow MRI with computational fluid dynamics (CFD) to address these limitations and to reconstruct de-noised, divergence-free high-resolution flow-fields. Proper orthogonal decomposition (POD) is used to construct the orthonormal basis of the local sampling of the space of all possible solutions to the flow equations both at the low-resolution level of the 4D Flow MRI grid and the high-level resolution of the CFD mesh. Low-resolution, de-noised flow is obtained by projecting in vivo 4D Flow MRI data onto the low-resolution basis vectors. Ridge regression is then used to reconstruct high-resolution de-noised divergence-free solution. The effects of 4D Flow MRI grid resolution, and noise levels on the resulting velocity fields are further investigated. A numerical phantom of the flow through a cerebral aneurysm was used to compare the results obtained using the POD method with those obtained with the state-of-the-art de-noising methods. At the 4D Flow MRI grid resolution, the POD method was shown to preserve the small flow structures better than the other methods, while eliminating noise. Furthermore, the method was shown to successfully reconstruct details at the CFD mesh resolution not discernible at the 4D Flow MRI grid resolution. This method will improve the accuracy of the clinically relevant flow-derived parameters, such as pressure gradients and wall shear stresses, computed from in vivo 4D Flow MRI data.

Computational Fluid Dynamics modeling of contrast transport in basilar aneurysms following flow-altering surgeries.

In vivo measurement of blood velocity fields and flow descriptors remains challenging due to image artifacts and limited resolution of current imaging methods; however, in vivo imaging data can be used to inform and validate patient-specific computational fluid dynamics (CFD) models. Image-based CFD can be particularly useful for planning surgical interventions in complicated cases such as fusiform aneurysms of the basilar artery, where it is crucial to alter pathological hemodynamics while preserving flow to the distal vasculature. In this study, patient-specific CFD modeling was conducted for two basilar aneurysm patients considered for surgical treatment. In addition to velocity fields, transport of contrast agent was simulated for the preoperative and postoperative conditions using two approaches. The transport of a virtual contrast passively following the flow streamlines was simulated to predict post-surgical flow regions prone to thrombus deposition. In addition, the transport of a mixture of blood with an iodine-based contrast agent was modeled to compare and verify the CFD results with X-ray angiograms. The CFD-predicted patterns of contrast flow were qualitatively compared to in vivo X-ray angiograms acquired before and after the intervention. The results suggest that the mixture modeling approach, accounting for the flow rates and properties of the contrast injection, is in better agreement with the X-ray angiography data. The virtual contrast modeling assessed the residence time based on flow patterns unaffected by the injection procedure, which makes the virtual contrast modeling approach better suited for prediction of thrombus deposition, which is not limited to the peri-procedural state.