Accelerated multi-contrast high isotropic resolution 3D intracranial vessel wall MRI using a tailored k-space undersampling and partially parallel reconstruction strategy

Intracranial vessel wall MRI is an emerging imaging technique that is gaining traction in the characterization and differentiation of intracranial vasculopathies [1]. IVW has preliminarily shown the ability to differentiate etiologies of steno-occlusive disease of the carotid termini better than luminal imaging alone [2], characterize vulnerable aneurysm [3] and intracranial atherosclerosis [4], and distinguish between non-occlusive intracranial vasculopathies [5]. The major limitations of IVW, specifically long scan times and increased signal demand, arise secondary to the spatial resolution demands necessary for the evaluation of the small intracranial arteries with thin walls and complex vessel geometry, with the recommendation of using sequences with 0.5-mm isotropic voxel size [6]. Moreover, lesion characterization/differentiation may benefit from a multi-contrast IVW protocol which includes several sequences [5] that may further extend IVW protocol scan times, contributing to increased patient discomfort, degraded image quality due to patient motion, and limiting the feasibility of performing routine clinical IVW scanning. Accelerated IVW protocols that can adequately maintain high resolution and signal-to-noise ratio (SNR) have the potential to promote clinical translation of the technique for improved vascular disease assessment.

Imaging acceleration algorithms recently have been receiving increased attention due to the possibility of shortening scan times while maintaining image quality. Cartesian undersampling with target ordering method (CUSTOM) [7] and self-supporting tailored k-space estimation for parallel imaging reconstruction (STEP) [8] are recently developed k-space undersampling and partially parallel imaging reconstruction algorithms that have shown improved reconstruction accuracy and reduced noise amplification relative to the other existing partially parallel imaging techniques such as SPIRiT [9] and SAKE [10].

The goal of this study was, therefore, to develop an accelerated three-dimensional (3D) multi-contrast IVW protocol with 0.5-mm isotropic resolution with a scan time of 5 min per sequence using CUSTOM + STEP technology and to evaluate its performance as compared to fully sampled data acquisition and to other clinically available methods for reducing acquisition time. Images were acquired from both normal volunteers and two patients with confirmed intracranial atherosclerotic disease (ICAD) and assessed to answer the following questions: (1) whether adequate vessel wall delineation can be obtained when compared to full-sample acquisition, (2) whether CUSTOM + STEP performance is better than current clinically available parallel imaging acceleration, and (3) whether performance of STEP reconstruction is better than standard zero-filled image reconstruction clinically available on the scanner.

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. A flowchart of MR imaging, reconstruction, and comparison steps is shown in Fig. 1.

We demonstrated a multi-contrast 3D 0.5-mm isotropic resolution IVW protocol (3D-WALLI) with a scan time of less than 30 min. 3D-WALLI consists of highly T1w SNAP, PDw DANTE prepared VISTA, T1w VISTA, and post-contrast T1w VISTA to enable comprehensive characterization of intracranial vasculopathies. The scan time of 5 min per sequence was achieved using CUSTOM k-space undersampling. The reduction in scan time per sequence and for the full 3D-WALLI protocol was designed to benefit high-resolution IVW by reducing the chances of motion blurring secondary to patient movement.

We employed CUSTOM k-space undersampling and STEP reconstruction methods for imaging acceleration while maintaining optimum vessel wall visualization. STEP is a partially parallel image reconstruction method that is tailored for magnetization prepared sequences such as vessel wall MRI sequences. STEP has been shown to provide improved vessel wall visualization [8] when compared to the other partially parallel imaging methods such as SPIRiT [9]. Compared to other k-space undersampling strategies such as variable density undersampling, CUSTOM is designed to provide consistently effective interpolation condition within local k-space regions for parallel imaging reconstruction while providing higher sampling density at the center of k-space for less aliasing artifact. Thus, CUSTOM provides adequate support for STEP reconstruction, and due to increased SNR, it is ideally suited for IVW.

IVW requires high spatial resolution, since the normal intracranial arterial wall is 0.2–0.3-mm-thick [6]. The previous studies have demonstrated the utility of high-resolution 2D cross-sectional IVW [16‐18]. These studies acquired one to a few 2-mm-thick slices perpendicular to the axis of the MCA or basilar artery. Unlike arteries with relatively straight courses such as the common carotid artery or abdominal aorta, segments of the intracranial vessels are tortuous and the location where lesions may form is variable. Thus, 3D isotropic sequences are important for IVW, such that multi-planar reformatting in arbitrary planes allows torturous vessels to be observed in cross section. In addition, increased brain coverage with 3D IVW as compared to 2D IVW allows for the detection and evaluation of multiple lesions, including culprit lesions that may not be prospectively detected on luminal imaging due to outward remodeling/lack of stenosis [19, 20].

Recent studies have demonstrated 3D isotropic scans for IVW [12, 21‐26]. A single contrast weighting was used in these studies to identify plaque with or without contrast injection. Two studies [27, 28] indicated the need for multi-contrast IVW and used three-to-four contrast weightings. In addition, multi-contrast protocols have shown value for intracranial vasculopathy differentiation [2, 5]. However, 3D IVW spatial resolutions of 0.6–0.8-mm isotropic and/or scan times per sequence of up to 12 min in those studies may be limiting for patients. In this study, both 0.5-mm isotropic resolution and 5–6-min scan times were targeted for broader applicability in IVW. 0.5-mm isotropic resolution is also recommended by the ASNR expert consensus document for IVW [6].

The value of specific contrast weightings as part of a multi-contrast IVW has been extensively investigated in extracranial carotid atherosclerotic plaques relative to histopathology. A multi-contrast protocol consisting of a highly T1w sequence, pre-contrast, and post-contrast T1w sequence and time-of-flight MRA are central for the assessment of plaque composition [29, 30] in extracranial carotid atherosclerotic disease. The requirements for IVW are less clear. We have chosen the contrast weightings in the current manuscript based on the recent consensus IVW document that suggests a protocol with TOF, pre-contrast T1, post-contrast T1, and T2 weightings. SNAP is a highly T1-weighted sequence used to identify intraplaque hemorrhage. SNAP also provides simultaneous angiography for stenosis assessment [13] in addition to 3D TOF. Pre-contrast and post-contrast T1w VISTA can be used to identify lipid core, loose matrix tissue and calcification, and to measure wall thickness. The proposed IVW protocol also acquires PDw VISTA as an intermediate contrast weighting instead of T2w VISTA. Use of DANTE prepulse with PDw VISTA allows complete suppression of cerebrospinal fluid required for identification of vessel wall. The normal vessel wall is difficult to distinguish on T2w VISTA due to bright CSF. T2w VISTA can, however, be substituted for PDw VISTA. CSF suppression ratings on CUSTOM + STEP were lower than fully sampled for the PDw VISTA comparison only and not on other comparisons. However, wall–CSF CNR measurements tended to be lower on CUSTOM + STEP for both PDw VISTA and T1w VISTA. The higher wall–CSF CNR measurement for fully sampled sequences was most likely due to the higher SNR and the perceived high brain tissue to CSF contrast likely led to higher CSF suppression ratings for fully sampled PDw VISTA.

A single fully sampled 0.5-mm isotropic scan in our study averaged 10 min for the T1 and PD contrast weightings which agrees with the other studies [23] with 0.56 mm isotropic resolution. Highly T1-weighted SNAP sequence at 0.5 mm requires multiple averages without CUSTOM to achieve sufficient image quality. Thus, the fully sampled 3D-WALLI protocol will require up to an hour without CUSTOM. Undersampling with CUSTOM provided two advantages with respect to protocol scan time. First, it allowed total scan time to be reduced to 30 min, even though two averages were acquired for all sequences. Second, the denser sampling of k-space center and averaging allowed for 0.5-mm isotropic SNAP MRI with joint STEP reconstruction. Joint STEP reconstruction was implemented in this work to utilize the higher SNR of SNAP reference image to improve reconstruction results. Thus, CUSTOM + STEP allowed 0.5-mm isotropic scans to be accelerated while improving image quality over fully sampled 0.5-mm isotropic scans. Reducing the scan time per sequence to 5 min and reducing the total protocol scan time are also expected to improve vessel wall visualization in patient studies through reduction in motion blurring secondary to patient movement.

Parallel imaging is clinically available on modern scanners for scan acceleration. We compared CUSTOM + STEP to SENSE for use in IVW. SENSE-accelerated 3D volumes had more severe SENSE fold-over artifacts, such that several images were not usable. In SNR constrained sequences such as T1w VISTA or SNAP, CUSTOM + STEP had higher image quality ratings compared to SENSE. Another option for scan acceleration is compressed sensing [31]. Compressed sensing is currently not available clinically and requires an undersampling and reconstruction strategy similar to CUSTOM + STEP. Variable density sampling and an L1 norm reconstruction with a wavelet domain transformation is customarily used for compressed sensing [31]. We note that CUSTOM undersampling is designed to support both parallel imaging and compressed sensing [7], and has been shown to reduce reconstruction error when compared to variable density sampling. STEP can also be combined with a wavelet basis and L1 norm minimization, and has been previously compared favorably against L1 SPIRiT [8].

Performance of CUSTOM + STEP was also compared to fully sampled acquisition. Image quality ratings confirmed similar performance especially for T1 VISTA and SNAP. While CNR was lower for CUSTOM + STEP than fully sampled, both subjective image quality rating and morphometric measurements were comparable. The reduction in CNR can be attributed to lower signal due to undersampling as shown by the reduced SNR_W on CUSTOM + STEP but comparable SNR_L on all sequences. However, the wall-to-lumen signal ratio and lumen area measurements on CUSTOM − STEP were comparable to fully sampled sequences, suggesting that vessel delineation is not impacted by the lower SNR. Perceptual image sharpness as shown by the PSI measure was better for CUSTOM + STEP despite the reduced blur measure. Wall area measurements were comparable to fully sampled sequences, suggesting that image sharpness required for morphometric measurements was sufficient.

Our study has the following limitations and scope for improvement. (1) Reconstruction was performed offline and such reconstructions are not clinically feasible considering workflow and volume of studies interpreted in most private and academic radiology practices. Performance of STEP reconstruction of IVW scans has not been previously demonstrated. This study shows that STEP can provide high-quality reconstruction of IVW and, therefore, justifies future efforts aimed at implementing online STEP reconstruction. (2) STEP reconstruction currently requires 20–70 min per sequence. Reconstruction times will need further increased efficiency if online reconstruction is to be implemented. GPU processors with additional cores are becoming increasingly available and may help to further reduce reconstruction times. (3) This technical development study compared CUSTOM + STEP image quality to fully sampled and SENSE-accelerated scans, and the optimized protocol was demonstrated using a limited number of subjects. While the comparison showed CUSTOM + STEP provides similar vessel wall delineation as fully sampled IVW and can be applied to patient studies, further evaluation in a wide range of ICAD lesions including large intracranial atherosclerotic plaques with multiple plaque components may be required to assess subtle differences between the imaging techniques. (4) The order of sequence acquisition was not random between CUSTOM undersampled and fully sampled scans. Thus, the effect of motion could not be ruled out when comparing the sequences. Future studies aimed at studying the effect of motion on high-resolution scans will be required to specifically study this effect.

CUSTOM + STEP acceleration allows acquisition of a multi-contrast 3D 0.5-mm isotropic IVW protocol within 30 min of scan time. CUSTOM + STEP is superior to SENSE for IVW. STEP reconstruction of CUSTOM undersampled IVW provides improved vessel wall delineation compared to zero-filled image reconstruction. The CUSTOM + STEP protocol is well tolerated by patients and shows good delineation of ICAD plaque. Although some quantitative and qualitative scores for CUSTOM − STEP were lower than fully sampled IVW, CUSTOM + STEP provides comparable vessel wall delineation as fully sampled IVW. Combined with the fact that CUSTOM + STEP sequences are much shorter, the CUSTOM − STEP may provide a clinically feasible alternative to fully sampled IVW.