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Purpose Hemodynamic alterations are indicative of cerebrovascular disease. However, the narrow and tortuous cerebrovasculature complicates image-based assessment, especially when quantifying relative pressure. Here, we present a systematic evaluation of image-based cerebrovascular relative pressure mapping, investigating the accuracy of the routinely used reduced Bernoulli (RB), the extended unsteady Bernoulli (UB), and the full-field virtual work-energy relative pressure ( ν WERP) method. Methods Patient-specific in silico models were used to generate synthetic cerebrovascular 4D Flow MRI, with RB, UB, and ν WERP performance quantified as a function of spatiotemporal sampling and image noise. Cerebrovascular relative pressures were also derived in 4D Flow MRI from healthy volunteers ( n = 8 ), acquired at two spatial resolutions (dx = 1.1 and 0.8 mm). Results The in silico analysis indicate that accurate relative pressure estimations are inherently coupled to spatial sampling: at dx = 1.0 mm high errors are reported for all methods; at dx = 0.5 mm ν WERP recovers relative pressures at a mean error of 0.02 ± 0.25 mm Hg, while errors remain higher for RB and UB (mean error of -2.18 ± 1.91 and -2.18 ± 1.87 mm Hg, respectively). The dependence on spatial sampling is also indicated in vivo, albeit with higher correlative dependence between resolutions using ν WERP (k = 0.64, R2 = 0.81 for dx = 1.1 vs. 0.8 mm) than with RB or UB (k = 0.04, R2 = 0.03, and k = 0.07, R2 = 0.07, respectively). Conclusion Image-based full-field methods such as ν WERP enable cerebrovascular relative pressure mapping; however, accuracy is directly dependent on utilized spatial resolution.

Dual-velocity encoded (dual-venc or DV) 4D flow MRI achieves wide velocity dynamic range and velocity-to-noise ratio (VNR), enabling accurate neurovascular flow characterization. To reduce scan time, we present interleaved dual-venc 4D Flow with independently prescribed, prospectively undersampled spatial resolution of the high-venc (HV) acquisition: Variable Spatial Resolution Dual Venc (VSRDV).A prototype VSRDV sequence was developed based on a Cartesian acquisition with eight-point phase encoding, combining PEAK-GRAPPA acceleration with zero-filling in phase and partition directions for HV. The VSRDV approach was optimized by varying z, the zero-filling fraction of HV relative to low-venc, between 0%-80% in vitro (realistic neurovascular model with pulsatile flow) and in vivo (n = 10 volunteers). Antialiasing precision, mean and peak velocity quantification accuracy, and test-retest reproducibility were assessed relative to reference images with equal-resolution HV and low venc (z = 0%).In vitro results for all z demonstrated an antialiasing true positive rate at least 95% forVSRDV allows up to 34.8% scan time reduction compared to PEAK-GRAPPA accelerated DV 4D Flow MRI, enabling large spatial coverage and dynamic range while maintaining VNR and velocity measurement accuracy.

Dual-venc 4D flow MRI, recently introduced for the assessment of intracranial hemodynamics, may provide a promising complementary approach to well-established tools such as transcranial Doppler ultrasound (TCD) and overcome some of their disadvantages. However, data comparing intracranial flow measures from dual-venc 4D flow MRI and TCD are lacking.To compare cerebral blood flow velocity measures derived from dual-venc 4D flow MRI and TCD.Prospective cohort.A total of 25 healthy participants (56 ± 4 years old, 44% female).A 3 T/dual-venc 4D flow MRI using a time-resolved three-dimensional phase-contrast sequence with three-dimensional velocity encoding.Peak velocity measurements in bilateral middle cerebral arteries (MCA) were quantified from dual-venc 4D flow MRI and TCD. The MRI data were quantified by two independent observers (S.M and Y.M.) and TCD was performed by a trained technician (A.L.M.). We assessed the agreement between 4D flow MRI and TCD measures, and the interobserver agreement of 4D flow MRI measurements.Peak velocity from MRI and TCD was compared using Bland-Altman analysis and coefficient of variance. Intraclass correlation coefficient (ICC) was used to assess MRI interobserver agreement. A P value lt; 0.05 was considered statistically significant.There was excellent interobserver agreement in dual-venc 4D flow MRI-based measurements of peak velocity in bilateral MCA (ICC = 0.97 and 0.96 for the left and right MCA, respectively). Dual-venc 4D flow MRI significantly underestimated peak velocity in the left and right MCA compared to TCD (bias = 0.13 [0.59, -0.33] m/sec and 0.15 [0.47, -0.17] m/sec, respectively). The coefficient of variance between dual-venc 4D flow MRI and TCD measurements was 26% for the left MCA and 22% for the right MCA.There was excellent interobserver agreement for the assessment of MCA peak velocity using dual-venc 4D flow MRI, and ≤20% under-estimation compared with TCD.3 TECHNICAL EFFICACY: Stage 2.

The development of cerebrovascular disease is tightly coupled to changes in cerebrovascular hemodynamics, with altered flow and relative pressure indicative of the onset, development, and acute manifestation of pathology. Image-based monitoring of cerebrovascular hemodynamics is, however, complicated by the narrow and tortuous vasculature, where accurate output directly depends on sufficient spatial resolution. To address this, we present a method combining dedicated deep learning and state-of-the-art 4D Flow MRI to generate super-resolution full-field images with coupled quantification of relative pressure using a physics-driven image processing approach. The method is trained and validated in a patient-specific in-silico cohort, showing good accuracy in estimating velocity (relative error: 12.0 ± 0.1%, mean absolute error (MAE): 0.07 ± 0.06 m/s at peak velocity), flow (relative error: 6.6 ± 4.7%, root mean square error (RMSE): 0.5 ± 0.1 mL/s at peak flow), and with maintained recovery of relative pressure through the circle of Willis (relative error: 11.0 ± 7.3%, RMSE: 0.3 ± 0.2 mmHg). Furthermore, the method is applied to an in-vivo volunteer cohort, effectively generating data at

A heart-transplanted patient is at risk of developing several complications such as rejection, which is one of the leading causes of deaths in the first year after the transplant. The regional myocardial motion is known to be depressed early on during rejection before the reduction in global systolic function. Therefore, early detection of regional anomalies is crucial. We use a magnetic resonance (MR) imaging method called tissue phase mapping (TPM) to capture regional myocardial motion of heart-transplanted patients in a longitudinal study. We compare the individual scans of the longitudinal study to a cohort of healthy volunteers to detect anomalies. We use a spatio-temporal visualization based on a radial layout where myocardial regions are laid out in an angular pattern similar to the American Heart Association (AHA) model and where the temporal dimension increases with increasing radius. We compute nested envelopes of central regions for the time series of each region and each of the three velocity directions using the concept of functional boxplots. We propose visual encodings to analyze regional anomalies of a scan of an individual patient dataset and perform a qualitative user study with medical experts. We extend this layout to the visual analysis of longitudinal data to monitor changes in regional anomalies of a patient for multiple scans taken at different times. We apply our approach to data from a longitudinal study of patients under observation after a heart-transplant procedure and evaluate this mechanism with medical and non-medical experts.

Purpose The cerebral arterial inflow, venous outflow, and Cerebrospinal fluid volume and flow are highly regulated in an equilibrium to maintain adequate cerebral perfusion as governed by the Monro-Kellie doctrine. Multiple neurological conditions had been associated with abnormalities in the cerebral venous system including multiple sclerosis and idiopathic intracranial hypertension, among others. We aim to quantitatively study the relationship and discrepancy between total cerebral blood flow (TCBF) and cerebral venous outflow (CVO), as well as the TCBF as a proportion of the cardiac output in adults and how it compares to the pediatric patients, and highlight the discrepancies. Materials and Methods 31 healthy volunteers (24 adults and 7 children) underwent 4D flow MR imaging for arterial evaluation and 2D CINE PC-MRI for venous evaluation in an IRB approved study. 3D volumetric ECG-gated PC-MRI data with 3-directional velocity encoding (4D flow MRI) was acquired for the arterial system. 2D CINE PC MRI was acquired for the venous system at both transverse sinuses. 4D flow MRI data was processed using in-house software tools in Matlab. We calculated the cumulative TCBF in ml/sec as the sum of inflow in the bilateral ICAs and basilar artery. The CVO was calculated as the sum of the flow in the bilateral transverse sinuses. The ratio of CVO to TCBF was calculated. Also, the TCBF as a percentage of cardiac output was calculated. Results A significant positive correlation between TCBF and CVO (r=0.81 and P Conclusions Both TCBF and CVO decrease with age, however unlike TCBF, there is no correlation between the decrease in CVO through the Transverse sinuses and age, which could suggest the early development of alternative venous drainage pathways through the emissary and extracranial veins. This could also explain the differential ratio of CVO to TCBF, which suggests that more than 20% of cerebral venous outflow in adults and more than 35% of outflow in Children are not through the Transverse sinuses in the supine position. Understanding the quantitative differences between TCBF and CVO in healthy volunteers could help identify and manage changes related to venous outflow abnormalities. Disclosures R. Abdalla: None. S. Schnell: None. M. Aristova: None. M. Hurley: None. S. Ansari: None. A. Shaibani: None.

Introduction: Hemodynamic alterations of intracranial atherosclerotic disease (ICAD) patients may be associated with increased risk of stroke. Dual- venc 4D Flow MRI can provide time-resolved 3D hemodynamics with large velocity dynamic range, but clinical utility is limited by labor intensive analysis. We developed an automated tool to simplify analysis, rapidly extract and visualize hemodynamic parameters, bringing 4D Flow MRI closer to clinical practice. Purpose: To demonstrate clinical feasibility of a new automated tool for extracting hemodynamic parameters based on 4D Flow MRI, and evaluate intracranial hemodynamics in individual ICAD patients relative to normative reference values. Methods: Intracranial dual- venc 4D Flow MRI was acquired in 59 healthy subjects (32M, 48±15Y) and 16 ICAD patients (12M, 62±14Y). An in-house Matlab tool was used to quantify velocity and flow in each Circle of Willis vessel. Hemodynamic measures from the controls were used to derive normative parameter estimates using polynomial fit as a function of age. A hemodynamic profile for each patient included computing percent difference of peak velocity (PV) and flow rate (FR) in each vessel compared to reference values (Fig.1a-c), and showing results in a diagram (Fig.1d). Results: Fig.1e shows results for ICAD patients. 93.8% of stenotic vessels showed normal FR suggesting intracranial hemodynamic compensation. 62.5% of stenotic vessels showed abnormal PV and 75% of patients showed increased PV in at least one vessel in affected hemisphere. Among 3 patients with compensatory collateral circulation, 2 patients had more than 3 vessels with increased PV. This suggests PV is a more sensitive marker of stenosis than FR. Conclusions: We demonstrate the feasibility of an automated tool used with 4D Flow MRI to interrogate intracranial hemodynamics in ICAD patients. It has considerable promise for identifying new noninvasive biomarkers for individualized stroke risk stratification.

Purpose To improve velocity-to-noise ratio (VNR) and dynamic velocity range of 4D flow magnetic resonance imaging (MRI) by using dual-velocity encoding (dual-venc) with k-t generalized autocalibrating partially parallel acquisition (GRAPPA) acceleration. Materials and Methods A dual-venc 4D flow MRI sequence with k-t GRAPPA acceleration was developed using a shared reference scan followed by three-directional low- and high-venc scans (repetition time / echo time / flip angle = 6.1 msec / 3.4 msec / 15°, temporal/spatial resolution = 43.0 msec/1.2 × 1.2 × 1.2 mm3). The high-venc data were used to correct for aliasing in the low-venc data, resulting in a single dataset with the favorable VNR of the low-venc but without velocity aliasing. The sequence was validated with a 3T MRI scanner in phantom experiments and applied in 16 volunteers to investigate its feasibility for assessing intracranial hemodynamics (net flow and peak velocity) at the major intracranial vessels. In addition, image quality and image noise were assessed in the in vivo acquisitions. Results All 4D flow MRI scans were acquired successfully with an acquisition time of 20 ± 4 minutes. The shared reference scan reduced the total acquisition time by 12.5% compared to two separate scans. Phantom experiments showed 51.4% reduced noise for dual-venc compared to high-venc and an excellent agreement of velocities (ρ = 0.8, P < 0.001). The volunteer data showed decreased noise in dual-venc data (54.6% lower) compared to high-venc, and improved image quality, as graded by two observers: fewer artifacts (P < 0.0001), improved vessel conspicuity (P < 0.0001), and reduced noise (P < 0.0001). Conclusion Dual-venc 4D flow MRI exhibits the superior VNR of the low-venc acquisition and reliably incorporates low- and high-velocity fields simultaneously. In vitro and in vivo data demonstrate improved flow visualization, image quality, and image noise. Level of Evidence: 2 Technical Efficacy: Stage 1 J. MAGN. RESON. IMAGING 2017;46:102–114

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. B 1 + transmit efficiency was optimized by B 1 + 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.

Introduction: Cerebral arteriovenous malformation (AVM) is the most common cause of hemorrhagic stroke in young adults. AVM affects the total blood flow to the brain as well as the extranidal flow distribution, yet quantitative data relating AVM hemodynamic parameters to hemorrhage risk are lacking. 4D Flow MRI provides time-resolved 3D blood flow velocity with full volumetric coverage of principal arteries and veins. This study aims to investigate the impact of anatomical differences in vessel connectivity on blood flow, and to identify potential quantitative biomarkers for AVM stroke risk stratification. Methods: 4D flow MRI was obtained for healthy controls (n = 26) and patients with unruptured AVM (n = 5, Fig. 1A). A semiautomated in-house tool was used to compute blood flow and peak velocity at multiple points per vessel from 4D flow data (Fig. 1B). Results and vessel connectivity are schematically summarized as a Flow Distribution Network Graph (FDNG) for group comparison and secondary metrics. Results: In the healthy cohort, we identified 3 main COW variants: A (complete COW, n = 13), B (no RPCOM, n = 5) and C (both PCOMs missing, n = 4). Group comparison FDNGs (Fig. 1C) show significant differences between groups A and B in RICA flow (p = 0.026) and right A/P flow ratio (p = 0.036). AVMs were characterized by total cerebral blood flow and flow diversion to the nidus. AVM draining veins had significantly higher peak velocity (p = 0.032) relative to feeding arteries than non-draining veins relative to non-feeding arteries and control venous/arterial ratios (p = 0.002, Fig. 1D). Conclusions: Network analysis of 4D flow MRI data can identify significant differences in flow distribution between normal variant groups and provide standardized metrics of AVM hemodynamics, including peak velocity, which specifically distinguishes AVM nidal flow. These metrics account for individual vascular network variation and may provide a path forward for risk stratification.

Introduction: While previous studies have shown a link between changes in aneurysmal wall shear stress (WSS) and risk of rupture, the association between the development of WSS variations and intra-aneurysmal hemodynamic flow patterns remain unknown. Understanding such link could potentially lead to novel early biomarkers for risk stratification of aneurysmal rupture. Aim: To assess the association between intra-aneurysmal flow patterns behavior and WSS in cerebral aneurysm patients. Methods: Time-resolved 3D blood flow velocities were acquired by dual-venc 4D flow MRI (kt-GRAPPA R=5, voxel size (1.0x 1.0 x 1.0 mm 3 ), TE/TR 3.5/6.2 ms, temporal resolution 57ms, venc low /venc high 50/100 cm/s) in 12 patients (66 ± 9 years, 8 F), who presented with a total of 14 cerebral aneurysms (average 10-time points per aneurysm synchronized with the cardiac cycle). Time-resolved median WSS was quantified over the 3D aneurysm surface. To quantify 3D blood flow pattern behavior from 4D Flow MRI, we used the fluid dynamics-based helicity metric. Helicity is a signed quantity that measures the strength and alignment between vortical pattern and blood flow directions. Helicity magnitudes take positive values at regions where both vortical pattern and blood flow align in the same direction while regions with opposing directions have negative values. Time-resolved positive and negative helicity were quantified separately by instantaneous volumetric median and correlated with WSS. Correlation was tested using pooled paired data of all acquired time points from all aneurysms (N=147 samples). Results: (Fig.1) Strong correlations were found between WSS and flow patterns behavior with the strongest correlation (R=0.91, p Conclusions: We revealed that intra-aneurismal blood flow pattern behavior strongly correlates with wall shear stress. These results may help in the future to identify early hemodynamic markers for risk of aneurysmal rupture.

Introduction: Despite medical management, 12% of patients with intracranial atherosclerotic disease (ICAD) experience recurrent stroke. Degree of stenosis, the current standard for risk stratification, does not reflect the hemodynamic significance of the lesion. We hypothesized that 4D flow MRI derived parameters including flow rate (FR) and peak velocity (PV) in major cerebral arteries, as well as the pressure drop (PD) in the atherosclerotic stenosis (AS) could be new imaging biomarkers for the hemodynamic impact of AS on local and global cerebrovascular flow redistribution. Methods: Intracranial dual- venc 4D flow MRI and time-of-flight (TOF) MRA were acquired in 23 controls and 13 ICAD patients at 3T (Fig. 1a). AS was graded as moderate (50-69%) and severe (70-99%) based on TOF MRA. 4D flow MRI data was corrected for phase offsets and noise and subsequently processed using an automated analysis tool (Fig. 1b-f). At each analysis plane (Fig.1e), the lumen region was determined from the TOF MRA (registered with 4D flow MRI), and area, PV and FR were calculated. The PD in AS was estimated from the Bernoulli equation using PV and area at AS and the area proximal to the AS. PV and FR ratios between left and right hemispheres for controls and affected to nonaffected hemispheres for patients were also calculated. Results: The PV ratio was significantly different (ranked sum test, p=0.003, Fig. 1g) between control and patient cohorts while FR ratio was similar (p=0.5). In addition, there was a significant correlation between PD in AS and PV ratio for the patient cohort (Spearman correlation, r=0.64, p=0.03, Fig. 1h). Conclusions: In this pilot study, we demonstrated the feasibility of two 4D flow MRI derived hemodynamic parameters, peak velocity and pressure drop, for the characterization of the impacts of ICAD on local and global cerebral flow distribution. Future studies are warranted to assess the prognostic value of these parameters for improved ICAD risk stratification.

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.

Purpose: Advanced imaging and automated image processing techniques were used to demonstrate the feasibility of 4D flow MRI as a clinical tool for assessment of intracranial hemodynamics in patients with intracranial atherosclerotic disease (ICAD). Introduction: ICAD patients have a high risk of stroke recurrence, which could be partly due to intracranial hemodynamic failure. Thus, it is critical to assess the impact of ICAD on cerebrovascular flow dynamics. Dual- venc 4D flow MRI allows the assessment of flow in major intracranial arteries and veins by providing a large dynamic range. A new automated post-processing tool was developed to ease the cumbersome processing task that hinders clinical application of 4D flow MRI. Method: Intracranial dual- venc 4D flow MRI (Fig 1a) was acquired in 20 healthy volunteers (12M, 43±18Y) and three ICAD patients: two men, 65Y with near occlusion and 43Y with 65% stenotic right MCAs and a 70Y woman with stenoses in PCAs and ACAs (> 50%). Post-processing included automated segmentation of vessels, extraction of centerlines, positioning multiple analysis cut-planes (1 mm inter-plane distance) along the vessels, and computing peak velocity (PK) and flow rate (FR) for each vessel (Fig. 1b and 1c). Results: Fig. 1d and 1e present cumulative results for the control subjects, which show the PV and FR left/right ratios are close to one. this suggests hemodynamic symmetry between left and right hemispheres for controls. For the 65M patient with RMCA stenosis, the PV ratio/FR ratio in ICA and MCA were 1.37/2.26 and 1.44/7.09. The 43M patient with stenotic RMCA showed asymmetry only in the MCA-FR (1.6). The 70F case had multiple stenoses with the most pronounced asymmetry in PCA-PV and -FR (0.42 and 0.6). Discussion: We demonstrated the feasibility of using dual- venc 4D flow MRI and automated flow analysis tool to quantify hemodynamic markers such as PV, FR and flow asymmetry in ICAD patients with the potential application for ICAD risk stratification.