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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.

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.

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.