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On the optimization of 3D inflow-based vascular-space-occupancy (iVASO) MRI for the quantification of arteriolar cerebral blood volume (CBVa)

Chunming Gu^1,2,3, Di Cao^1,2,3, Xinyuan Miao^2,3, Adrian G Paez^2,3, Jitong Cai¹, Yinghao Li^1,2,3, Wenbo Li^2,3, Jay J Pillai^4,5, Peter C.M. van Zijl^2,3, and Jun Hua^2,3
¹Biomedical Engineering, Johns Hopkins University, Baltimore, MD, United States, ²Neurosection, Division of MRI Research, Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, United States, ³F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, United States, ⁴Division of Neuroradiology, Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, United States, ⁵Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD, United States

Synopsis

The iVASO MRI is a noninvasive approach for quantitative mapping of CBVa in the brain. It was originally developed in the single-slice mode. Recently, CBVa measured by single-slice iVASO has been validated using histological markers of arteriolar blood vessels in a mouse model. Here, we demonstrate an optimized 3D iVASO MRI protocol with a 3D turbo-field-echo (TFE) readout and a whole-brain coverage. It showed consistent CBVa measures when compared to the original single-slice iVASO. In 3D-TFE-iVASO, the imaging slab volume did not show significant effects on the measured CBVa values. CBVa measured with 3D-TFE-iVASO showed reasonable intra-subject reproducibility.

Introduction

The inflow-based vascular-space-occupancy (iVASO)^1-6 MRI is a noninvasive approach for the measurement of cerebral-blood-volume in small pial arteries and arterioles (CBVa). In iVASO, CBVa is calculated from the difference signal between an arterial blood nulled image and a control image without blood nulling. To account for the heterogeneity of vascular transit times, images are acquired at multiple post-inversion times (TI), from which absolute CBVa can be quantified². The arterial origin is confirmed experimentally by measuring the T2 of the difference signal in iVASO², as arterial blood T2 is distinct from that of venous blood, extravascular tissue and CSF. The iVASO method has been applied in several brain diseases^6-14. The iVASO MRI was originally developed in the single-slice mode using a gradient-echo (GRE) echo-planar-imaging (EPI) readout^1-6. Recently, CBVa measured by single-slice iVASO has been validated using histological markers of arteriolar blood vessels in a mouse model¹⁰. The iVASO method was later expanded to a three-dimensional (3D) mode covering most of the brain^11-14. A 3D turbo-field-echo (TFE) was adopted as the readout for 3D-iVASO, which has less signal dropout and geometric distortion compared to the previously used EPI sequence¹⁵. In this study, we aim to optimize 3D-iVASO MRI and evaluate it by comparing the results with the original single-slice iVASO. An improved numerical fitting algorithm was implemented for the quantitative analysis of CBVa, and two 3D-iVASO protocols with different coverage (imaging slab volume) were evaluated. Reproducibility of 3D-iVASO MRI was evaluated.

Method

Five healthy subjects (age=27.2±4.4 years; gender=2F/3M) were scanned on a 3T Philips MRI scanner. The following scans were performed in each participant: (1) 3D-TFE whole-brain iVASO: voxel=3x3x6mm³; 19 slices; flip-angle=20°; TR/TI=403/191, 600/277, 800/360, 1000/437, 1500/611, 2000/757, 2700/921, 3500/1059ms; 4 nulling/control pairs in each TI; TE=1.7ms; shot number=5; readout echo-train length=108.8ms; TFE-factor=29; Compressed Sensing-Sensitivity Encoding (CS-SENSE)=7; partial-Fourier=0.8; turbo-direction=radial. A reference scan (TR=20000ms, others the same as iVASO) through the ventricle was acquired to calculate the scaling factor M0². (2) 3D-TFE partial-brain iVASO: 9 slices; shot number=2; other parameters the same as (1). The center of the partial-brain volume was aligned with that of the whole-brain iVASO scan. (3) 2D-GRE-EPI single-slice iVASO: flip-angle=20°; TE=25ms; SENSE(AP)=2; and voxel and TR/TI the same as those in 3D iVASO scans. Three sets of single-slice scans were performed at three different locations corresponding the 6^th, 10^th (middle) and 14^th slices in the whole-brain 3D-iVASO scans (Figure 1). (4) MPRAGE: TR/TE/TI=8.1/3.7/749ms; CS-SENSE=8; voxel=1x1x1mm³; 150 slices. (5) A low-resolution MPRAGE with the same resolution and coverage as the whole-brain 3D-iVASO scan to assist the alignment between iVASO and MPRAGE. Note that in all three 3D and 2D iVASO scans, the flip-back slab was kept identical (thickness=126mm). For each participant, the same whole-brain 3D-iVASO scan was repeated within 2 weeks after the initial scan to evaluate its reproducibility.

Data analysis was performed using the SPM12 software and in-house MATLAB scripts. The surrounding subtraction method¹⁶ was used to calculate the difference signals between the nulled and control images in iVASO. A voxel-by-voxel fitting was conducted to calculate CBVa maps from the multi-TI iVASO difference signal using the Metropolis-Hastings algorithm^17,18. Compared to the commonly used least-square algorithm, the Metropolis-Hastings algorithm is more suitable and robust for data with relatively low signal-to-noise ratio (SNR) such as iVASO, arterial spin labeling (ASL)¹⁹, and diffusion MRI^20-22. Six regions-of-interest (ROI: grey matter (GM), white matter (WM), cuneus, precentral gyrus, postcentral gyrus, dorsal anterior cingulate cortex (ACC)) were identified on the anatomical images using MRICloud^23-25 and mean CBVa values were recorded in each ROI. To compare results from the three different iVASO protocols, paired Wilcoxon test was performed in each region. Coefficient of variation (CV) was computed to assess the scan-rescan reproducibility of the repeated scans, which is defined as the standard deviation of the difference between scan and rescan divided by the average signal intensity in each ROI²⁶.

Results

Figure 2 shows the representative images of the difference signals in iVASO (Sdiff) at each TI and the fitted CBVa map from the whole-brain and partial-brain 3D-iVASO scans and the single-slice iVASO scan. Quantitative results of the fitted CBVa from the three iVASO protocols are compared in each ROI in Figure 3. No significant difference was observed between the two 3D-iVASO scans, and between the 3D whole-brain and 2D single-slice iVASO scans. Reproducibility of CBVa measured by the whole-brain 3D-iVASO MRI scan is shown in Table 1.

Discussion & Conclusion

We demonstrate an optimized 3D-iVASO MRI protocol with a 3D-TFE readout and a whole-brain coverage. It shows consistent CBVa measures when compared to the original single-slice iVASO scan. The single-slice iVASO is used as a gold standard here as it has recently been validated using histological markers of arterioles in a mouse model¹⁰. In 3D-TFE-iVASO, the imaging slab volume did not show significant effects on the measured CBVa values. Therefore, this 3D-iVASO protocol can be tailored to different coverage for various applications. The CBVa values measured with the 3D-TFE-iVASO showed reasonable intra-subject reproducibility. Results from this technical study will serve as the basis for future clinical studies applying iVASO MRI in various brain diseases.

Acknowledgements

This study is supported by DoD (PD160104), NINDS (1R01NS108452), NIA (1R01AG064093), NIBIB (P41EB031771), and NICHD (U54 HD079123).

References

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Figures

Figure 1. Illustration of the positions of the imaging slabs in the whole-brain (19 slices), partial-brain (9 slices) and three single-slice (a, b, c) iVASO MRI scans performed in this study.

Figure 2. Representative images of the difference signals in iVASO (Sdiff) at each TI (shortest to longest) and the fitted CBVa map from one subject. In each scan, the slice corresponding to the middle slice of the whole-brain iVASO scan was shown. (A) 3D whole-brain iVASO MRI scan. (B) 3D partial-brain iVASO MRI scan. (C) 2D single-slice iVASO MRI scan.

Figure 3. Comparison of the fitted CBVa values from the whole-brain, partial-brain and single-slice iVASO MRI scans (n = 5). (A) 3D partial-brain vs. 3D whole-brain iVASO; (B) 2D single-slice vs. 3D whole-brain iVASO. The same slices in the corresponding protocols are compared. Note that the slices from the 3D whole-brain iVASO scans are different in (A) and (B).

Table 1. Reproducibility of CBVa measured using the whole-brain 3D iVASO MRI scans: coefficient of variation (%) by region of interest (ROI) (n = 5).

Proc. Intl. Soc. Mag. Reson. Med. 30 (2022)

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DOI: https://doi.org/10.58530/2022/4900