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Cerebrovascular Peak-Velocity Mapping in Intracranial Atherosclerotic Disease (ICAD) using 4D Flow MRI
Jackson E Moore1, Deima Koko1, Kelly Jarvis1, Abhinav Patel1, Adam Richter1, Ramez Abdalla1, Maria Aristova1, Ann Ragin1, Fan Caprio2, Sameer A Ansari1, Susanne Schnell1,3, and Michael Markl4
1Radiology, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States, 2Neurology, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States, 3Department of Medical Physics, University of Greifswald, Greifswald, Germany, 4Radiology, Northwestern University, Chicago, IL, United States

Synopsis

Keywords: Blood vessels, Atherosclerosis

Intracranial atherosclerotic disease (ICAD) accounts for 10-50% of acute ischemic strokes and is a leading cause of global morbidity and mortality. We used a semi-automated voxel-wise velocity-based mapping approach to visualize and quantify global and regional peak velocities (PVs) in the Circle of Willis (CoW) in 31 ICAD patients with moderate to severe MCA or ICA stenosis and 23 healthy controls. Our findings indicate 4D flow MRI-based cerebrovascular PV mapping can detect asymmetric PV distribution in the CoW on hemispheric and vessel levels. Future work will include investigation of PV asymmetry measures in the assessment of ICAD progression and outcomes.

Background

ICAD causes up to 10% of acute ischemic strokes in North America1 and up to 50% in Asia, making it a leading cause of morbidity and mortality globally2,3. Strokes secondary to ICAD have high likelihood of recurrence (12-25% over 1-2 years)4, driving the need for robust analysis. Luminal stenosis is the universally accepted marker of disease progression in ICAD5. However, available evidence indicates that regional measures of ICAD severity alone (i.e. lumen dimeter) cannot fully capture the impact of the lesion on cerebrovascular hemodynamic changes in the Circle of Willis (CoW)6-10.

In this context, 4D flow MRI is a versatile tool for measurement of global and regional 3D velocity data with full volumetric coverage of the entire CoW11,12. Our previous intracranial 4D flow studies have shown significant hemodynamic asymmetries, including peak velocity (PV) and pressure changes in ICAD patients compared to controls8,10. The purpose of this study was to further investigate the impact of ICAD with known severity grades on changes in CoW velocities and resulting asymmetries between the affected brain hemispheres in a large cohort of ICAD patients and compared to healthy controls. Additionally, this study introduces a velocity-based and voxel-wise analysis approach for intuitive visualization and quantification of global, hemispheric, and regional PVs in the CoW. We hypothesized elevated global PV and increased asymmetry in ICAD patients compared to controls.

Methods

31 ICAD patients (62.5 ± 13.6 years, 16F) with either middle cerebral artery (MCA) stenosis (n=23: 16 severe, 7 moderate) or internal carotid artery (ICA) stenosis (n=8: 5 severe, 3 moderate) and 23 healthy controls (36.3 ± 16.3 years, 4F) with no cerebrovascular disease history were included in this IRB-approved study. Two experienced neuroradiologists (S.A.A. and R.A.) used the WASID method to quantify stenosis grading13,14. Vessels were classified as severe if >70%, moderate if >50% and mild if 30-49% stenosis.

Patients underwent a comprehensive ICAD protocol on a 3T MRI system (MAGNETOM Skyra, Siemens, Erlangen, Germany), including dual-venc 4D flow MRI (TR=5.7-6.6 ms, TE=3.1-4.4 ms, flip angle=15°, low/high venc=60/120 cm/s, voxel size=1.0 mm isometric, temporal resolution=82-84 ms, k-t PEAK-GRAPPA15 acceleration factor of R = 5, approximate scan time=8-10 minutes).

All 4D flow data were corrected for Maxwell fields during reconstruction16. Eddy current, noise17, and velocity aliasing were corrected with in-house software tools18. A time-averaged 3D phase contrast angiogram (PC-MRA) was calculated to depict vessel anatomy. The CoW and vessels were manually segmented from the PC-MRA using dedicated software (Mimics Innovation Suite, Materialise, Leuven, Belgium, Figure 1A-B). The 3D CoW segmentation was used to mask the 4D flow data and derive parametric peak velocity maps using in-house analysis tools (MATLAB, MathWorks, Natick, MA) similar to a previously used workflow19 adapted for intracranial analysis. For each voxel within the CoW segmentation, absolute velocity v(t) was determined at each cardiac timepoint and the systolic time frames of the cardiac cycle were used to quantify PV. The resulting CoW peak velocity distribution was visualized as a maximum intensity projection (MIP) with anatomic background from the 4D flow magnitude data (Figure 1C). Data analysis further included quantification of global and regional intracranial asymmetry ratio difference (ARD) comparing PV of affected vs unaffected hemispheres (in ICAD) or left vs right hemisphere (in controls, with expected ARD of 1 showing symmetric values). To account for different hemodynamic compensation scenarios (Figure 2), ARD was calculated as follows:

$$ Asymmetry\,Ratio\,Difference = \left|\frac{PV_{Affected}}{PV_{Unaffected}} - 1 \right| $$

Results

Global CoW PV was significantly elevated (Fig. 3) in all patients and ICA stenosis patients compared to controls (All: 0.85 ± 0.27 m/s, p = 0.043; MCA Stenosis: 0.80 ± 0.26 m/s, p = 0.22; ICA Stenosis: 1.00 ± 0.26 m/s, p = 0.001; vs controls: 0.72 ± 0.16 m/s).

Asymmetry analysis results (Table 1; Fig. 4) demonstrated significantly increased ARD for all ICAD patients in brain hemispheres and for individual vessels. Similar to previous studies, in the moderate MCA stenosis group, PVs in both hemispheres, ICAs, and ACAs were not significantly elevated, indicating only minor impact of these ICAD lesions on changes in global velocity destitution in the CoW. In contrast, patients with severe MCA ICAD showed substantial PV asymmetry in the MCAs, ICAs, and PCAs, evidence for the systemic effect of these focal ICAD stenoses on redistribution of intracranial flow velocities (Fig 2). Both moderate and severe ICA stenosis had similar effects on ARD at both the vessel and hemisphere levels.

Discussion and Conclusion

These findings demonstrate the feasibility of the intracranial peak velocity mapping workflow for the intuitive visualization and quantification of ICAD impact on global and regional distribution of peak velocities in the entire CoW. For ICAD patients with severe MCA or moderate to severe ICA stenosis, the majority of CoW vessel segments showed elevated peak velocity asymmetry, indicating a marked effect of these focal lesions on the distribution of intracranial velocities. Our study did not consider other hemodynamic measures, such as flow, pressure differences, or kinetic energy, that would be needed for a more complete characterization of CoW hemodynamics in ICAD. Further, manual 3D segmentation of the CoW is time-consuming. Future studies could integrate these measures and examine the automation of analysis for efficient hemodynamic analysis in larger cohorts.

Acknowledgements

This work was funded by the National Institute of Health (NIH NIA P30AG059988, NIH 1R01HL149787, NIH 1R21NS122511).

References

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Figures

Figure 1: Analysis workflow. A) 4D flow MRI of intracranial vessels was preprocessed and used to generate PCMRA. B) CoW segmentation showing filtered voxels in red. Patient has severe LMCA stenosis and right P1 anatomical variant. C) Qualitative maximum intensity projection of PV. CoW mask was truncated with an ROI for the middle cerebral artery at the M1/M2 branch point and the anterior cerebral artery at the A1/A2 branch point. The 95th to 98th velocity percentiles were used to characterize PV.

Figure 2: Left - Severe MCA stenosis patient with narrowed vessel causing increased velocity due to flow jet. Affected / Unaffected hemisphere asymmetry index of 1.4. Right – Severe MCA stenosis patient (near-occlusion) with signal dropout at stenosis location. Contralateral hemisphere shows clear signs of flow compensation with thickened vessels and increased PV. Asymmetry index of 0.66. Cohort patterns include 8 with flow jets, 13 with contralateral compensation, and 9 with symmetric compensation.

Table 1: Asymmetry Differences. Mean values represent the difference from perfect symmetry between hemispheres. Statistically significant comparisons to controls are marked in bold. Groups are: all ICAD patients, all patients with a primary MCA or ICA stenosis, and moderate or severe subgroups for each. A Student’s t-test was used to compare normally distributed data; the Wilcoxon rank sum test was used otherwise.

Figure 3: Peak velocity for the entire CoW analysis region. Relative to controls, all ICAD patients are significantly increased, MCA stenosis patients are not increased and exhibit compensation and ICA stenosis patients are significantly increased likely due to increased compensatory flow through the contralateral ICA.

Figure 4: Hemispheric and vessel ARD with p-values representing patient results compared to controls. All ICAD patients are separated on x-axes by primary stenosis site (MCA or ICA), with corresponding moderate and severe stenosis subgroups.

Proc. Intl. Soc. Mag. Reson. Med. 31 (2023)
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DOI: https://doi.org/10.58530/2023/2312