Optimized interferometric encoding of presaturated TurboFLASH B1 mapping for parallel transmission MRI at 7 T: Preliminary application for quantitative T1 mapping in the spinal cord.

PURPOSE: The acquisition of accurate B1 maps is critical for parallel transmit techniques (pTx). The presaturated turboFLASH (satTFL) method has been widely used in combination with interferometric encoding to provide robust and fast B1 maps. However, typical encodings, mostly evaluated on brain, do not necessarily fit all coils and organs. In this work, we evaluated and improved the accuracy of the satTFL for cervical spine at 7 T, proposing a novel interferometric encoding optimization. The benefits of such improvements were investigated in an exploratory study of quantitative T1 mapping with pTx-MP2RAGE. METHODS: Global optimization of interferometric encoding was implemented by simulating the ability of the satTFL to reconstruct B1 maps, with varying encoding and inclusion of complex noise, inside a region of interest covering the cervical spine. The performance of satTFL before and after optimization was compared to actual flip angle imaging. Optimized and non-optimized B1 maps were then used to calculate pTx pulses for MP2RAGE T1 mapping. RESULTS: Interferometric encoding optimization resulted in satTFL closer to actual flip angle imaging, with substantial gain of signal in regions where non-optimized satTFL could fail. T1 maps measured with non-adiabatic pTx pulses were closer to standard non-pTx results (which used adiabatic pulses) when using optimized-satTFL, with substantially lower specific absorption rate. CONCLUSION: Optimization of the satTFL interferometric encoding improves B1 maps in the spinal cord, in particular in low SNR regions. A linear correction of the satTFL was additionally shown to be required. The method was successfully used for quantitative phantom and in vivo T1 mapping, showing improved results compared to non-optimized satTFL thanks to improved pTx-pulse generation.

Respiratory-triggered quantitative MR spectroscopy of the human cervical spinal cord at 7 T.

PURPOSE: Ultra-high field 1 H MR spectroscopy (MRS) is of great interest to help characterizing human spinal cord pathologies. However, very few studies have been reported so far in this small size structure at these fields due to challenging experimental difficulties caused by static and radiofrequency field heterogeneities, as well as physiological motion. In this work, in line with the recent developments proposed to strengthen spinal cord MRS feasibility at 7 T, a respiratory-triggered acquisition approach was optimized to compensate for dynamic B 0 field heterogeneities and to provide robust cervical spinal cord MRS data. METHODS: A semi-LASER sequence was purposely used, and a dedicated raw data processing algorithm was developed to enhance MR spectral quality by discarding corrupted scans. To legitimate the choices done during the optimization stage, additional tests were carried out to determine the impact of breathing, voluntary motion, body mass index, and fitting algorithm. An in-house quantification tool was concomitantly designed for accurate estimation of the metabolite concentration ratios for choline, N-acetyl-aspartate (NAA), myo-inositol and glutathione. The method was tested on a cohort of 14 healthy volunteers. RESULTS: Average water linewidth and NAA signal-to-noise ratio reached 0.04 ppm and 11.01, respectively. The group-average metabolic ratios were in good agreement with previous studies and showed intersession reproducibility variations below 30%. CONCLUSION: The developed approach allows a rise of the acquired MRS signal quality and of the quantification robustness as compared to previous studies hence offering strengthened possibilities to probe the metabolism of degenerative and traumatic spinal cord pathologies.

Feasibility of human spinal cord perfusion mapping using dynamic susceptibility contrast imaging at 7T: Preliminary results and identified guidelines.

PURPOSE: To explore the feasibility of dynamic susceptibility contrast MRI at 7 Tesla for human spinal cord perfusion mapping and fill the gap between brain and spinal cord perfusion mapping techniques. METHODS: Acquisition protocols for high-resolution single shot EPI in the spinal cord were optimized for both spin-echo and gradient-echo preparations, including cardiac gating, acquisition times and breathing cycle recording. Breathing-induced MRI signal fluctuations were investigated in healthy volunteers. A specific image- and signal-processing pipeline was implemented to address them. Dynamic susceptibility contrast was then evaluated in 3 healthy volunteers and 5 patients. Bolus depiction on slice-wise signal within cord was investigated, and maps of relative perfusion indices were computed. RESULTS: Signal fluctuations were increased by 1.9 and 2.3 in free-breathing compared to apnea with spin-echo and gradient-echo, respectively. The ratio between signal fluctuations and bolus peak in healthy volunteers was 5.0% for spin-echo and 3.8% for gradient-echo, allowing clear depiction of the bolus on every slice and yielding relative blood flow and volume maps exhibiting the expected higher perfusion of gray matter. However, signal fluctuations in patients were increased by 4 in average (using spin-echo), compromising the depiction of the bolus in slice-wise signal. Moreover, 3 of 18 slices had to be discarded because of fat-aliasing artifacts. CONCLUSION: Dynamic susceptibility contrast MRI at 7 Tesla showed great potential for spinal cord perfusion mapping with a reliability never achieved thus far for single subject and single slice measurements. Signal stability needs to be improved in acquisition conditions associated with patients; guidelines to achieve that have been identified and shared.

Multiple sclerosis lesions in motor tracts from brain to cervical cord: spatial distribution and correlation with disability.

Despite important efforts to solve the clinico-radiological paradox, correlation between lesion load and physical disability in patients with multiple sclerosis remains modest. One hypothesis could be that lesion location in corticospinal tracts plays a key role in explaining motor impairment. In this study, we describe the distribution of lesions along the corticospinal tracts from the cortex to the cervical spinal cord in patients with various disease phenotypes and disability status. We also assess the link between lesion load and location within corticospinal tracts, and disability at baseline and 2-year follow-up. We retrospectively included 290 patients (22 clinically isolated syndrome, 198 relapsing remitting, 39 secondary progressive, 31 primary progressive multiple sclerosis) from eight sites. Lesions were segmented on both brain (T2-FLAIR or T2-weighted) and cervical (axial T2- or T2*-weighted) MRI scans. Data were processed using an automated and publicly available pipeline. Brain, brainstem and spinal cord portions of the corticospinal tracts were identified using probabilistic atlases to measure the lesion volume fraction. Lesion frequency maps were produced for each phenotype and disability scores assessed with Expanded Disability Status Scale score and pyramidal functional system score. Results show that lesions were not homogeneously distributed along the corticospinal tracts, with the highest lesion frequency in the corona radiata and between C2 and C4 vertebral levels. The lesion volume fraction in the corticospinal tracts was higher in secondary and primary progressive patients (mean = 3.6 ± 2.7% and 2.9 ± 2.4%), compared to relapsing-remitting patients (1.6 ± 2.1%, both P < 0.0001). Voxel-wise analyses confirmed that lesion frequency was higher in progressive compared to relapsing-remitting patients, with significant bilateral clusters in the spinal cord corticospinal tracts (P < 0.01). The baseline Expanded Disability Status Scale score was associated with lesion volume fraction within the brain (r = 0.31, P < 0.0001), brainstem (r = 0.45, P < 0.0001) and spinal cord (r = 0.57, P < 0.0001) corticospinal tracts. The spinal cord corticospinal tracts lesion volume fraction remained the strongest factor in the multiple linear regression model, independently from cord atrophy. Baseline spinal cord corticospinal tracts lesion volume fraction was also associated with disability progression at 2-year follow-up (P = 0.003). Our results suggest a cumulative effect of lesions within the corticospinal tracts along the brain, brainstem and spinal cord portions to explain physical disability in multiple sclerosis patients, with a predominant impact of intramedullary lesions.

Anterior fissure, central canal, posterior septum and more: New insights into the cervical spinal cord gray and white matter regional organization using T1 mapping at 7T.

T1 mapping lacks specificity toward a single particular biological feature, however it has the potential to discriminate spinal cord regional tissue organization and characterize tissue microstructural impairments occurring in neurodegenerative pathologies. In this exploratory work, T1 mapping of the cervical spinal cord with a 300-µm in-plane resolution was performed on fourteen healthy subjects at 7T, using the MP2RAGE sequence. Individual images from C1 to C7 vertebral levels provided a clear delineation of spinal cord anatomical details and substructures including motor columns within gray matter (GM) horns, anterior median fissure, central canal, ventral, lateral and dorsal white matter (WM) fasciculi, and posterior median septum. Group studies highlighted regional T1 differences between regions of interest so far hardly visible at lower spatial resolution. Two-dimensional averaged T1 maps and manual parcellation of GM and WM substructures were built based on these data. Benefiting from the very high spatial resolution achievable at ultra-high field for T1 mapping, this work contributes to improve the in vivo characterization of the cervical spinal cord. By allowing investigation within a wider range of functional regions, it also opens new perspectives for pathology diagnosis such as motor neuron disease, neuropathic pain or refined investigation of neurodegeneration.

Intravoxel Incoherent Motion at 7 Tesla to quantify human spinal cord perfusion: limitations and promises.

PURPOSE: To develop a noninvasive technique to map human spinal cord (SC) perfusion in vivo. More specifically, to implement an intravoxel incoherent motion (IVIM) protocol at ultrahigh field for the human SC and assess parameters estimation errors. METHODS: Monte-Carlo simulations were conducted to assess estimation errors of 2 standard IVIM fitting approaches (two-step versus one-step fit) over the range of IVIM values reported for the human brain and for typical SC diffusivities. Required signal-to-noise ratio (SNR) was inferred for estimation of the parameters product, fIVIM D* (microvascular fraction times pseudo-diffusion coefficient), within 10% error margins. In-vivo IVIM imaging of the SC was performed at 7T in 6 volunteers. An image processing pipeline is proposed to generate IVIM maps and register them for an atlas-based region-wise analysis. RESULTS: Required b = 0 SNRs for 10% error estimation on fIVIM D* with the one-step fit were 159 and 185 for diffusion-encoding perpendicular and parallel to the SC axis, respectively. Average in vivo b = 0 SNR within cord was 141 ± 79, corresponding to estimation errors of 12.7% and 14.7% according to numerical simulations. Slice- and group-averaging reduced noise in IVIM maps, highlighting the difference in perfusion between gray and white matter. Mean ± standard deviation fIVIM and D* values across subjects within gray (respectively white) matter were 16.0 ± 1.7 (15.0 ± 1.6)% and 11.4 ± 2.9 (11.5 ± 2.4) × 10-3 mm2 /s. CONCLUSION: Single-subject data SNR at 7T was insufficient for reliable perfusion estimation. However, atlas-averaged IVIM maps highlighted the higher microvascular fraction of gray matter compared to white matter, providing first results of healthy human SC perfusion mapping with MRI.

Spatial distribution of multiple sclerosis lesions in the cervical spinal cord.

Spinal cord lesions detected on MRI hold important diagnostic and prognostic value for multiple sclerosis. Previous attempts to correlate lesion burden with clinical status have had limited success, however, suggesting that lesion location may be a contributor. Our aim was to explore the spatial distribution of multiple sclerosis lesions in the cervical spinal cord, with respect to clinical status. We included 642 suspected or confirmed multiple sclerosis patients (31 clinically isolated syndrome, and 416 relapsing-remitting, 84 secondary progressive, and 73 primary progressive multiple sclerosis) from 13 clinical sites. Cervical spine lesions were manually delineated on T2- and T2*-weighted axial and sagittal MRI scans acquired at 3 or 7 T. With an automatic publicly-available analysis pipeline we produced voxelwise lesion frequency maps to identify predilection sites in various patient groups characterized by clinical subtype, Expanded Disability Status Scale score and disease duration. We also measured absolute and normalized lesion volumes in several regions of interest using an atlas-based approach, and evaluated differences within and between groups. The lateral funiculi were more frequently affected by lesions in progressive subtypes than in relapsing in voxelwise analysis (P < 0.001), which was further confirmed by absolute and normalized lesion volumes (P < 0.01). The central cord area was more often affected by lesions in primary progressive than relapse-remitting patients (P < 0.001). Between white and grey matter, the absolute lesion volume in the white matter was greater than in the grey matter in all phenotypes (P < 0.001); however when normalizing by each region, normalized lesion volumes were comparable between white and grey matter in primary progressive patients. Lesions appearing in the lateral funiculi and central cord area were significantly correlated with Expanded Disability Status Scale score (P < 0.001). High lesion frequencies were observed in patients with a more aggressive disease course, rather than long disease duration. Lesions located in the lateral funiculi and central cord area of the cervical spine may influence clinical status in multiple sclerosis. This work shows the added value of cervical spine lesions, and provides an avenue for evaluating the distribution of spinal cord lesions in various patient groups.

Automatic segmentation of the spinal cord and intramedullary multiple sclerosis lesions with convolutional neural networks.

The spinal cord is frequently affected by atrophy and/or lesions in multiple sclerosis (MS) patients. Segmentation of the spinal cord and lesions from MRI data provides measures of damage, which are key criteria for the diagnosis, prognosis, and longitudinal monitoring in MS. Automating this operation eliminates inter-rater variability and increases the efficiency of large-throughput analysis pipelines. Robust and reliable segmentation across multi-site spinal cord data is challenging because of the large variability related to acquisition parameters and image artifacts. In particular, a precise delineation of lesions is hindered by a broad heterogeneity of lesion contrast, size, location, and shape. The goal of this study was to develop a fully-automatic framework - robust to variability in both image parameters and clinical condition - for segmentation of the spinal cord and intramedullary MS lesions from conventional MRI data of MS and non-MS cases. Scans of 1042 subjects (459 healthy controls, 471 MS patients, and 112 with other spinal pathologies) were included in this multi-site study (n = 30). Data spanned three contrasts (T1-, T2-, and T2∗-weighted) for a total of 1943 vol and featured large heterogeneity in terms of resolution, orientation, coverage, and clinical conditions. The proposed cord and lesion automatic segmentation approach is based on a sequence of two Convolutional Neural Networks (CNNs). To deal with the very small proportion of spinal cord and/or lesion voxels compared to the rest of the volume, a first CNN with 2D dilated convolutions detects the spinal cord centerline, followed by a second CNN with 3D convolutions that segments the spinal cord and/or lesions. CNNs were trained independently with the Dice loss. When compared against manual segmentation, our CNN-based approach showed a median Dice of 95% vs. 88% for PropSeg (p ≤ 0.05), a state-of-the-art spinal cord segmentation method. Regarding lesion segmentation on MS data, our framework provided a Dice of 60%, a relative volume difference of -15%, and a lesion-wise detection sensitivity and precision of 83% and 77%, respectively. In this study, we introduce a robust method to segment the spinal cord and intramedullary MS lesions on a variety of MRI contrasts. The proposed framework is open-source and readily available in the Spinal Cord Toolbox.

Regional T1 mapping of the whole cervical spinal cord using an optimized MP2RAGE sequence.

The recently-proposed MP2RAGE sequence was purposely optimized for cervical spinal cord imaging at 3T. Sequence parameters were chosen to optimize gray/white matter T1 contrast with sub-millimetric resolution and scan-time < 10 min while preserving reliable T1 determination with minimal B1+ variation effects within a range of values compatible with pathologies and surrounding structures. Results showed good agreements with IR-based measurements, high MP2RAGE-based T1 reproducibility and preliminary evidences of age- and tract-related T1 variations in the healthy spinal cord.

While T1 measurements present multiple challenges (robustness, acquisition time), the recently proposed MP2RAGE sequence (magnetization-prepared two rapid acquisition gradient echoes) has opened new perspectives to characterize tissue microstructure changes occurring in a pathological or developmental context. Extensively used for brain studies, it was herein adapted to investigate the cervical spinal cord (SC) at 3 T. By integrating Bloch equations, the MP2RAGE sequence parameters were chosen to optimize SC gray matter/white matter (GM/WM) T1 contrast with sub-millimetric resolution, a scan time less than 10 min and a reliable T1 determination with minimal B1+ variation effect, within a range of values compatible with different pathologies and surrounding structures. The residual B1+ effect on T1 values was corrected using a look-up-table approach and B1+ mapping. The accuracy of B1+ -corrected T1 measurements was assessed on a phantom with respect to conventional inversion recovery. In vivo MP2RAGE acquisitions were performed on five young (28.8 ± 4.3 years old) and five elderly (60.2 ± 2.9 years old) volunteers and analyzed using a template-based approach. Phantom experiments led to high agreements between inversion-recovery spin-echo and MP2RAGE-based T1 values (R2  = 0.997). In vivo T1 values for cervical WM, anterior GM (aGM), posterior sensory tracts (PSTs) and lateral motor tracts (LMTs) were 917 ± 29 s, 934 ± 33 ms, 920 ± 37 ms and 877 ± 35 ms, respectively, with all subjects and cervical levels considered. Significant differences were observed between aGM and LMTs, and between LMTs and PSTs, in agreement with the literature. Repeated T1 measurements demonstrated high reproducibility of the MP2RAGE in the SC (variation coefficient < 5% in all regions of interest). Finally, preliminary assessment of age-related SC tissue microstructure variation additionally showed evidence of SC atrophy and slight trends of T1 decrease with age in all regions. Overall, this study shows that fast, robust and accurate sub-millimetric resolution T1 mapping in the cervical SC using the MP2RAGE sequence is possible, paving the way for future multi-centric and longitudinal clinical studies investigating the pathological cord.

Measurement of magnetization transfer ratio (MTR) from cervical spinal cord: Multicenter reproducibility and variability.

BACKGROUND: Assessing the multicenter variability of magnetization transfer ratio (MTR) measurements in the spinal cord of healthy controls is the first step toward investigating its clinical use as a biomarker. PURPOSE: To analyze the between-session, between-participant, and between-scanner variability of MTR measurements in automatically extracted regions of interest in the cervical cord of healthy controls. STUDY TYPE: Control study. POPULATION: Forty-four participants, distributed across five MRI scanners (all from the same manufacturer). Ten participants were scanned twice in the same scanner, and 10 others were scanned twice in two different scanners. FIELD STRENGTH/SEQUENCE: 3D-gradient echo images, centered on C5, without and with magnetization transfer prepulse at 3T. ASSESSMENT: We calculated the mean MTR for different vertebral levels in the whole cord (WC), as well as in the white matter and gray matter, and determined the between-session, between-participant, and between-scanner variabilities. STATISTICAL TESTS: Coefficients of variation and intraclass correlations (ICCs) for the different variabilities and their associated confidence intervals. RESULTS: The MTR measurements for Levels C4-C6 (near the slab center) exhibited a mean value in WC of 34.6 pu and a pooled standard deviation of 0.9 pu. The between-session coefficient of variation was estimated as 2.3% (ICC = 0.63), the between-participant coefficient as 1.6% (ICC = 0.32), and the between-scanner coefficient as 0.7% (ICC = 0.05). The resulting aggregate coefficient of variation was 2.9%, which was sufficiently low to detect an MTR reduction of 1 pu between groups of about 45 participants (Type-I error rate: 0.05; Type-II error rate: 0.10). DATA CONCLUSION: The good between-scanner reproducibility and low overall variability in cervical spinal cord MTR measurements in a control population might pave the way for multicenter analyses in various neurological diseases with moderate cohort sizes. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:1777-1785.

Focal and diffuse cervical spinal cord damage in patients with early relapsing-remitting MS: A multicentre magnetisation transfer ratio study.

BACKGROUND: Studies including patients with well-established multiple sclerosis (MS) have shown a significant and disability-related reduction in the cervical spinal cord (SC) magnetisation transfer ratio (MTR). OBJECTIVES: The objectives are to (1) assess whether MTR reduction is already measurable in the SC of patients with early relapsing-remitting multiple sclerosis (RRMS) and (2) describe its spatial distribution. METHODS: We included 60 patients with RRMS <12 months and 34 age-matched controls at five centres. Axial T2*w, sagittal T2w, sagittal phase-sensitive inversion recovery (PSIR), 3DT1w, and axial magnetisation transfer (MT) images were acquired from C1 to C7. Lesions were manually labelled and mean MTR values computed both for the whole SC and for normal-appearing SC in different regions of interest. RESULTS: Mean whole SC MTR was significantly lower in patients than controls (33.7 vs 34.9 pu, p = 0.00005), even after excluding lesions (33.9 pu, p = 0.0003). We observed a greater mean reduction in MTR for vertebral levels displaying the highest lesion loads (C2-C4). In the axial plane, we observed a greater mean MTR reduction at the SC periphery and barycentre. CONCLUSION: Cervical SC tissue damage measured using MTR is not restricted to macroscopic lesions in patients with early RRMS and is not homogeneously distributed.

Use of magnetic resonance image registration to estimate displacement in the human earcanal due to the insertion of in-ear devices.

In-ear devices are used in a wide range of applications for which the device's usability and/or efficiency is strongly related to comfort aspects that are influenced by the mechanical interaction between the device and the walls of the earcanal. Although the displacement of the earcanal walls due to the insertion of the device is an important characteristic of this interaction, existing studies on this subject are very limited. This paper proposes a method to estimate this displacement in vivo using a registration technique on magnetic resonance images. The amplitude, the location and the direction of the earcanal wall displacement are computed for four types of earplugs used by one participant. These displacements give indications on how each earplug deforms the earcanal for one specific earcanal geometry and one specific earplug insertion. Although the displacement due to a specific earplug family cannot be generalized using the results of this paper, the latter help to understand where, how much, and how each studied earplug deforms the earcanal of the participant. This method is revealed as a promising tool to investigate further acoustical and physical comfort aspects of in-ear devices.

PAM50: Unbiased multimodal template of the brainstem and spinal cord aligned with the ICBM152 space.

Template-based analysis of multi-parametric MRI data of the spinal cord sets the foundation for standardization and reproducibility, thereby helping the discovery of new biomarkers of spinal-related diseases. While MRI templates of the spinal cord have been recently introduced, none of them cover the entire spinal cord. In this study, we introduced an unbiased multimodal MRI template of the spinal cord and the brainstem, called PAM50, which is anatomically compatible with the ICBM152 brain template and uses the same coordinate system. The PAM50 template is based on 50 healthy subjects, covers the full spinal cord (C1 to L2 vertebral levels) and the brainstem, is available for T1-, T2-and T2*-weighted MRI contrasts and includes a probabilistic atlas of the gray matter and white matter tracts. Template creation accuracy was assessed by computing the mean and maximum distance error between each individual spinal cord centerline and the PAM50 centerline, after registration to the template. Results showed high accuracy for both T1- (mean = 0.37 ± 0.06 mm; max = 1.39 ± 0.58 mm) and T2-weighted (mean = 0.11 ± 0.03 mm; max = 0.71 ± 0.27 mm) contrasts. Additionally, the preservation of the spinal cord topology during the template creation process was verified by comparing the cross-sectional area (CSA) profile, averaged over all subjects, and the CSA profile of the PAM50 template. The fusion of the PAM50 and ICBM152 templates will facilitate group and multi-center studies of combined brain and spinal cord MRI, and enable the use of existing atlases of the brainstem compatible with the ICBM space.

Fully-integrated framework for the segmentation and registration of the spinal cord white and gray matter.

The spinal cord white and gray matter can be affected by various pathologies such as multiple sclerosis, amyotrophic lateral sclerosis or trauma. Being able to precisely segment the white and gray matter could help with MR image analysis and hence be useful in further understanding these pathologies, and helping with diagnosis/prognosis and drug development. Up to date, white/gray matter segmentation has mostly been done manually, which is time consuming, induces a bias related to the rater and prevents large-scale multi-center studies. Recently, few methods have been proposed to automatically segment the spinal cord white and gray matter. However, no single method exists that combines the following criteria: (i) fully automatic, (ii) works on various MRI contrasts, (iii) robust towards pathology and (iv) freely available and open source. In this study we propose a multi-atlas based method for the segmentation of the spinal cord white and gray matter that addresses the previous limitations. Moreover, to study the spinal cord morphology, atlas-based approaches are increasingly used. These approaches rely on the registration of a spinal cord template to an MR image, however the registration usually doesn't take into account the spinal cord internal structure and thus lacks accuracy. In this study, we propose a new template registration framework that integrates the white and gray matter segmentation to account for the specific gray matter shape of each individual subject. Validation of segmentation was performed in 24 healthy subjects using T2*-weighted images, in 8 healthy subjects using diffusion weighted images (exhibiting inverted white-to-gray matter contrast compared to T2*-weighted), and in 5 patients with spinal cord injury. The template registration was validated in 24 subjects using T2*-weighted data. Results of automatic segmentation on T2*-weighted images was in close correspondence with the manual segmentation (Dice coefficient in the white/gray matter of 0.91/0.71 respectively). Similarly, good results were obtained in data with inverted contrast (diffusion-weighted image) and in patients. When compared to the classical template registration framework, the proposed framework that accounts for gray matter shape significantly improved the quality of the registration (comparing Dice coefficient in gray matter: p=9.5×10-6). While further validation is needed to show the benefits of the new registration framework in large cohorts and in a variety of patients, this study provides a fully-integrated tool for quantitative assessment of white/gray matter morphometry and template-based analysis. All the proposed methods are implemented in the Spinal Cord Toolbox (SCT), an open-source software for processing spinal cord multi-parametric MRI data.

SCT: Spinal Cord Toolbox, an open-source software for processing spinal cord MRI data.

For the past 25 years, the field of neuroimaging has witnessed the development of several software packages for processing multi-parametric magnetic resonance imaging (mpMRI) to study the brain. These software packages are now routinely used by researchers and clinicians, and have contributed to important breakthroughs for the understanding of brain anatomy and function. However, no software package exists to process mpMRI data of the spinal cord. Despite the numerous clinical needs for such advanced mpMRI protocols (multiple sclerosis, spinal cord injury, cervical spondylotic myelopathy, etc.), researchers have been developing specific tools that, while necessary, do not provide an integrative framework that is compatible with most usages and that is capable of reaching the community at large. This hinders cross-validation and the possibility to perform multi-center studies. In this study we introduce the Spinal Cord Toolbox (SCT), a comprehensive software dedicated to the processing of spinal cord MRI data. SCT builds on previously-validated methods and includes state-of-the-art MRI templates and atlases of the spinal cord, algorithms to segment and register new data to the templates, and motion correction methods for diffusion and functional time series. SCT is tailored towards standardization and automation of the processing pipeline, versatility, modularity, and it follows guidelines of software development and distribution. Preliminary applications of SCT cover a variety of studies, from cross-sectional area measures in large databases of patients, to the precise quantification of mpMRI metrics in specific spinal pathways. We anticipate that SCT will bring together the spinal cord neuroimaging community by establishing standard templates and analysis procedures.

Magnetization transfer from inhomogeneously broadened lines (ihMT): Improved imaging strategy for spinal cord applications.

PURPOSE: Inhomogeneous magnetization transfer (ihMT) shows great promise for specific imaging of myelinated tissues. Whereas the ihMT technique has been previously applied in brain applications, the current report presents a strategy for cervical spinal cord (SC) imaging free of cerebrospinal fluid (CSF) pulsatility artifacts. METHODS: A pulsed ihMT preparation was combined with a single-shot HASTE readout. Electrocardiogram (ECG) synchronization was used to acquire all images during the quiescent phase of SC motion. However ihMT signal quantification errors may occur when a variable recovery delay is introduced in the sequence as a consequence of variable cardiac cycle. A semiautomatic retrospective correction algorithm, based on repetition time (TR) -matching, is proposed to correct for signal variations of long T1 -components (e.g., CSF). RESULTS: The proposed strategy combining ECG synchronization and retrospective data pairing led to clean SC images free of CSF artifacts. Lower variability of the ihMT metrics were obtained with the correction algorithm, and allowed for shorter TR to be used, hence improving signal-to-noise ratio efficiency. CONCLUSION: The proposed methodology enabled faster acquisitions, while offering robust ihMT quantification and exquisite SC image quality. This opens great perspectives for widening the in vivo characterization of SC physiopathology using MRI, such as studying white matter tracts microstructure or impairment in degenerative pathologies. Magn Reson Med 77:581-591, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Region-specific impairment of the cervical spinal cord (SC) in amyotrophic lateral sclerosis: A preliminary study using SC templates and quantitative MRI (diffusion tensor imaging/inhomogeneous magnetization transfer).

In this preliminary study, our objective was to investigate the potential of high-resolution anatomical imaging, diffusion tensor imaging (DTI) and conventional/inhomogeneous magnetization transfer imaging [magnetization transfer (MT)/inhomogeneous magnetization transfer (ihMT)] at 3 T, analyzed with template-extracted regions of interest, to measure the atrophy and structural changes of white (WM) and gray (GM) matter spinal cord (SC) occurring in patients with amyotrophic lateral sclerosis (ALS). Ten patients with ALS and 20 age-matched healthy controls were recruited. SC GM and WM areas were automatically segmented using dedicated templates. Atrophy indices were evaluated from T2 *-weighted images at each vertebral level from cervical C1 to C6. DTI and ihMT metrics were quantified within the corticospinal tract (CST), posterior sensory tract (PST) and anterior GM (aGM) horns at the C2 and C5 levels. Clinical disabilities of patients with ALS were evaluated using the Revised ALS Functional Rating Scale, upper motor neuron (UMN) and Medical Research Council scorings, and correlated with MR metrics. Compared with healthy controls, GM and WM atrophy was observed in patients with ALS, especially at lower cervical levels, where a strong correlation was also observed between GM atrophy and the UMN score (R = -0.75, p = 0.05 at C6). Interestingly, a significant decrease in ihMT ratio was found in all regions of interest (p < 0.0008), fractional anisotropy (FA) and MT ratios decreased significantly in CST, especially at C5 (p < 0.005), and λ// (axial diffusivity) decreased significantly in CST (p = 0.0004) and PST (p = 0.003) at C2. Strong correlations between MRI metrics and clinical scores were also found (0.47 < |R| < 0.87, p < 0.05). Altogether, these preliminary results suggest that high-resolution anatomical imaging and ihMT imaging, in addition to DTI, are valuable for the characterization of SC tissue impairment in ALS. In this study, in addition to an important SC WM demyelination, we also observed, for the first time in ALS, impairments of cervical aGM.

Topologically preserving straightening of spinal cord MRI.

PURPOSE: To propose a robust and accurate method for straightening magnetic resonance (MR) images of the spinal cord, based on spinal cord segmentation, that preserves spinal cord topology and that works for any MRI contrast, in a context of spinal cord template-based analysis. MATERIALS AND METHODS: The spinal cord curvature was computed using an iterative Non-Uniform Rational B-Spline (NURBS) approximation. Forward and inverse deformation fields for straightening were computed by solving analytically the straightening equations for each image voxel. Computational speed-up was accomplished by solving all voxel equation systems as one single system. Straightening accuracy (mean and maximum distance from straight line), computational time, and robustness to spinal cord length was evaluated using the proposed and the standard straightening method (label-based spline deformation) on 3T T2 - and T1 -weighted images from 57 healthy subjects and 33 patients with spinal cord compression due to degenerative cervical myelopathy (DCM). RESULTS: The proposed algorithm was more accurate, more robust, and faster than the standard method (mean distance = 0.80 vs. 0.83 mm, maximum distance = 1.49 vs. 1.78 mm, time = 71 vs. 174 sec for the healthy population and mean distance = 0.65 vs. 0.68 mm, maximum distance = 1.28 vs. 1.55 mm, time = 32 vs. 60 sec for the DCM population). CONCLUSION: A novel image straightening method that enables template-based analysis of quantitative spinal cord MRI data is introduced. This algorithm works for any MRI contrast and was validated on healthy and patient populations. The presented method is implemented in the Spinal Cord Toolbox, an open-source software for processing spinal cord MRI data. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2017;46:1209-1219.

High-resolution multi-parametric quantitative magnetic resonance imaging of the human cervical spinal cord at 7T.

Quantitative MRI techniques have the potential to characterize spinal cord tissue impairments occurring in various pathologies, from both microstructural and functional perspectives. By enabling very high image resolution and enhanced tissue contrast, ultra-high field imaging may offer further opportunities for such characterization. In this study, a multi-parametric high-resolution quantitative MRI protocol is proposed to characterize in vivo the human cervical spinal cord at 7T. Multi-parametric quantitative MRI acquizitions including T1, T2* relaxometry mapping and axial diffusion MRI were performed on ten healthy volunteers with a whole-body 7T system using a commercial prototype coil-array dedicated to cervical spinal cord imaging. Automatic cord segmentation and multi-parametric data registration to spinal cord templates enabled robust regional studies within atlas-based WM tracts and GM horns at the C3 cervical level. T1 value, cross-sectional area and GM/WM ratio evolutions along the cervical cord were also reported. An original correction method for B1+-biased T1 mapping sequence was additionally proposed and validated on phantom. As a result, relaxometry and diffusion parameters derived from high-resolution quantitative MRI acquizitions were reported at 7T for the first time. Obtained images, with unmatched resolutions compared to lower field investigations, provided exquisite anatomical details and clear delineation of the spinal cord substructures within an acquisition time of 30min, compatible with clinical investigations. Regional statistically significant differences were highlighted between WM and GM based on T1 and T2* maps (p<10-3), as well as between sensory and motor tracts based on diffusion tensor imaging maps (p<0.05). The proposed protocol demonstrates that ultra-high field spinal cord high-resolution quantitative MRI is feasible and lays the groundwork for future clinical investigations of degenerative spinal cord pathologies.

Tract-specific and age-related variations of the spinal cord microstructure: a multi-parametric MRI study using diffusion tensor imaging (DTI) and inhomogeneous magnetization transfer (ihMT).

Being able to finely characterize the spinal cord (SC) microstructure and its alterations is a key point when investigating neural damage mechanisms encountered in different central nervous system (CNS) pathologies, such as multiple sclerosis, amyotrophic lateral sclerosis or myelopathy. Based on novel methods, including inhomogeneous magnetization transfer (ihMT) and dedicated SC probabilistic atlas post-processing, the present study focuses on the in vivo characterization of the healthy SC tissue in terms of regional microstructure differences between (i) upper and lower cervical vertebral levels and (ii) sensory and motor tracts, as well as differences attributed to normal aging. Forty-eight healthy volunteers aged from 20 to 70 years old were included in the study and scanned at 3 T using axial high-resolution T2 *-w imaging, diffusion tensor imaging (DTI) and ihMT, at two vertebral levels (C2 and C5). A processing pipeline with minimal user intervention, SC segmentation and spatial normalization into a reference space was implemented in order to assess quantitative morphological and structural parameters (cross-sectional areas, scalar DTI and MT/ihMT metrics) in specific white and gray matter regions of interest. The multi-parametric MRI metrics collected allowed upper and lower cervical levels to be distinguished, with higher ihMT ratio (ihMTR), higher axial diffusivity (λ∥ ) and lower radial diffusivity (λ⊥ ) at C2 compared with C5. Significant differences were also observed between white matter fascicles, with higher ihMTR and lower λ∥ in motor tracts compared with posterior sensory tracts. Finally, aging was found to be associated with significant metric alterations (decreased ihMTR and λ∥ ). The methodology proposed here, which can be easily transferred to the clinic, provides new insights for SC characterization. It bears great potential to study focal and diffuse SC damage in neurodegenerative and demyelinating diseases. Copyright © 2016 John Wiley & Sons, Ltd.