ASL lexicon and reporting recommendations: A consensus report from the ISMRM Open Science Initiative for Perfusion Imaging (OSIPI).

The 2015 consensus statement published by the International Society for Magnetic Resonance in Medicine (ISMRM) Perfusion Study Group and the European Cooperation in Science and Technology ( COST) Action ASL in Dementia aimed to encourage the implementation of robust arterial spin labeling (ASL) perfusion MRI for clinical applications and promote consistency across scanner types, sites, and studies. Subsequently, the recommended 3D pseudo-continuous ASL sequence has been implemented by most major MRI manufacturers. However, ASL remains a rapidly and widely developing field, leading inevitably to further divergence of the technique and its associated terminology, which could cause confusion and hamper research reproducibility. On behalf of the ISMRM Perfusion Study Group, and as part of the ISMRM Open Science Initiative for Perfusion Imaging (OSIPI), the ASL Lexicon Task Force has been working on the development of an ASL Lexicon and Reporting Recommendations for perfusion imaging and analysis, aiming to (1) develop standardized, consensus nomenclature and terminology for the broad range of ASL imaging techniques and parameters, as well as for the physiological constants required for quantitative analysis; and (2) provide a community-endorsed recommendation of the imaging parameters that we encourage authors to include when describing ASL methods in scientific reports/papers. In this paper, the sequences and parameters in (pseudo-)continuous ASL, pulsed ASL, velocity-selective ASL, and multi-timepoint ASL for brain perfusion imaging are included. However, the content of the lexicon is not intended to be limited to these techniques, and this paper provides the foundation for a growing online inventory that will be extended by the community as further methods and improvements are developed and established.

Fast-spin-echo versus rapid gradient-echo for 3D magnetization-prepared acquisitions: Application to inhomogeneous magnetization transfer.

PURPOSE: To evaluate the benefits of fast spin echo (FSE) imaging over rapid gradient-echo (RAGE) for magnetization-prepared inhomogeneous magnetization transfer (ihMT) imaging. METHODS: A 3D FSE sequence was modified to include an ihMT preparation (ihMT-FSE) with an optional CSF suppression based on an inversion-recovery (ihMT-FLAIR). After numeric simulations assessing SNR benefits of FSE and the potential impact of an additional inversion-recovery, ihMT-RAGE, ihMT-FSE, and ihMT-FLAIR sequences were compared in a group of six healthy volunteers, evaluating image quality, thermal, and physiological noise as well as quantification using an ihMT saturation (ihMTsat) approach. A preliminary exploration in the cervical spinal cord was also conducted in a group of three healthy volunteers. RESULTS: Several fold improvements in thermal SNR were observed with ihMT-FSE in agreement with numerical simulations. However, we observed significantly higher physiological noise in ihMT-FSE compared to ihMT-RAGE that was mitigated in ihMT-FLAIR, which provided the best total SNR (+74% and +49% compared to ihMT-RAGE in the white and gray matter, P ≤ 0.004). IhMTsat quantification was successful in all cases with strong correlation between all sequences (r2 > 0.75). Early experiments showed potential for spinal cord imaging. CONCLUSIONS: FSE generally offers higher SNR compared to gradient-echo based acquisitions for magnetization-prepared contrasts as illustrated here in the case of ihMT. However, physiological noise has a significant effect, but an inversion-recovery-based CSF suppression was shown to be efficient in mitigating effects of CSF motion.

Update on state-of-the-art for arterial spin labeling (ASL) human perfusion imaging outside of the brain.

This review article provides an overview of developments for arterial spin labeling (ASL) perfusion imaging in the body (i.e., outside of the brain). It is part of a series of review/recommendation papers from the International Society for Magnetic Resonance in Medicine (ISMRM) Perfusion Study Group. In this review, we focus on specific challenges and developments tailored for ASL in a variety of body locations. After presenting common challenges, organ-specific reviews of challenges and developments are presented, including kidneys, lungs, heart (myocardium), placenta, eye (retina), liver, pancreas, and muscle, which are regions that have seen the most developments outside of the brain. Summaries and recommendations of acquisition parameters (when appropriate) are provided for each organ. We then explore the possibilities for wider adoption of body ASL based on large standardization efforts, as well as the potential opportunities based on recent advances in high/low-field systems and machine-learning. This review seeks to provide an overview of the current state-of-the-art of ASL for applications in the body, highlighting ongoing challenges and solutions that aim to enable more widespread use of the technique in clinical practice.

Vasculopathy and Increased Vascular Congestion in Fatal COVID-19 and Acute Respiratory Distress Syndrome.

Rationale: The leading cause of death in coronavirus disease 2019 (COVID-19) is severe pneumonia, with many patients developing acute respiratory distress syndrome (ARDS) and diffuse alveolar damage (DAD). Whether DAD in fatal COVID-19 is distinct from other causes of DAD remains unknown. Objective: To compare lung parenchymal and vascular alterations between patients with fatal COVID-19 pneumonia and other DAD-causing etiologies using a multidimensional approach. Methods: This autopsy cohort consisted of consecutive patients with COVID-19 pneumonia (n = 20) and with respiratory failure and histologic DAD (n = 21; non-COVID-19 viral and nonviral etiologies). Premortem chest computed tomography (CT) scans were evaluated for vascular changes. Postmortem lung tissues were compared using histopathological and computational analyses. Machine-learning-derived morphometric analysis of the microvasculature was performed, with a random forest classifier quantifying vascular congestion (CVasc) in different microscopic compartments. Respiratory mechanics and gas-exchange parameters were evaluated longitudinally in patients with ARDS. Measurements and Main Results: In premortem CT, patients with COVID-19 showed more dilated vasculature when all lung segments were evaluated (P = 0.001) compared with controls with DAD. Histopathology revealed vasculopathic changes, including hemangiomatosis-like changes (P = 0.043), thromboemboli (P = 0.0038), pulmonary infarcts (P = 0.047), and perivascular inflammation (P < 0.001). Generalized estimating equations revealed significant regional differences in the lung microarchitecture among all DAD-causing entities. COVID-19 showed a larger overall CVasc range (P = 0.002). Alveolar-septal congestion was associated with a significantly shorter time to death from symptom onset (P = 0.03), length of hospital stay (P = 0.02), and increased ventilatory ratio [an estimate for pulmonary dead space fraction (Vd); p = 0.043] in all cases of ARDS. Conclusions: Severe COVID-19 pneumonia is characterized by significant vasculopathy and aberrant alveolar-septal congestion. Our findings also highlight the role that vascular alterations may play in Vd and clinical outcomes in ARDS in general.

Recent Technical Developments in ASL: A Review of the State of the Art.

This review article provides an overview of a range of recent technical developments in advanced arterial spin labeling (ASL) methods that have been developed or adopted by the community since the publication of a previous ASL consensus paper by Alsop et al. It is part of a series of review/recommendation papers from the International Society for Magnetic Resonance in Medicine Perfusion Study Group. Here, we focus on advancements in readouts and trajectories, image reconstruction, noise reduction, partial volume correction, quantification of nonperfusion parameters, fMRI, fingerprinting, vessel selective ASL, angiography, deep learning, and ultrahigh field ASL. We aim to provide a high level of understanding of these new approaches and some guidance for their implementation, with the goal of facilitating the adoption of such advances by research groups and by MRI vendors. Topics outside the scope of this article that are reviewed at length in separate articles include velocity selective ASL, multiple-timepoint ASL, body ASL, and clinical ASL recommendations.

Characterization of the cortical myeloarchitecture with inhomogeneous magnetization transfer imaging (ihMT).

BACKGROUND: Myelin specific imaging techniques to characterize white matter in demyelinating diseases such as multiple sclerosis (MS) have become an area of increasing focus. Gray matter myelination is an important marker of cortical microstructure, and its impairment is relevant in progressive MS. However, its assessment is challenging due to its thin layers. While myelin water imaging and ultra-short TE imaging have not yet been implemented to assess cortical myeloarchitecture, magnetization transfer (MT) shows promise. A recent development of the MT technique, ihMT, has demonstrated greater myelin sensitivity/specificity. Here we implemented a 3D ihMT acquisition and analysis to characterize cortical gray matter myeloarchitecture. METHODS: 20 young healthy volunteers were imaged with a 3D ihMTRAGE sequence and quantitative metrics of ihMT (ihMTsat), and dual frequency-offset MT (dual MTsat) were calculated. Cortical surface-based analysis of ihMTsat and dual MTsat were performed and compared. We also compared the cortical ihMTsat map to a cortical surface-based map of T1-weighted images (T1w), defined as a proxy of myelin content. RESULTS: Cortical ihMTsat and dual MTsat maps were in qualitative agreement with previous work and the cortical T1w map, showing higher values in primary cortices and lower values in the insula. IhMTsat and dual MTsat were significantly correlated but with important regional differences. The ratio ihMTsat/dual MTsat highlighted higher ihMTsat values in the primary cortices and sulci. CONCLUSION: ihMTsat, a quantitative metric of ihMT, can be reliably measured in cortical gray matter and shows unique contrast between cortical regions.

Rotated spiral RARE for high spatial and temporal resolution volumetric arterial spin labeling acquisition.

BACKGROUND: Arterial Spin Labeling (ASL) MRI can provide quantitative images that are sensitive to both time averaged blood flow and its temporal fluctuations. 3D image acquisitions for ASL are desirable because they are more readily compatible with background suppression to reduce noise, can reduce signal loss and distortion, and provide uniform flow sensitivity across the brain. However, single-shot 3D acquisition for maximal temporal resolution typically involves degradation of image quality through blurring or noise amplification by parallel imaging. Here, we report a new approach to accelerate a common stack of spirals 3D image acquisition by pseudo golden-angle rotation and compressed sensing reconstruction without any degradation of time averaged blood flow images. METHODS: 28 healthy volunteers were imaged at 3T with background-suppressed unbalanced pseudo-continuous ASL combined with a pseudo golden-angle Stack-of-Spirals 3D RARE readout. A fully-sampled perfusion-weighted volume was reconstructed by 3D non-uniform Fast Fourier Transform (nuFFT) followed by sum-of-squares combination of the 32 individual channels. Coil sensitivities were estimated followed by reconstruction of the 39 single-shot volumes using an L1-wavelet Compressed-Sensing reconstruction. Finally, brain connectivity analyses were performed in regions where BOLD signal suffers from low signal-to-noise ratio and susceptibility artifacts. RESULTS: Image quality, assessed with a non-reference 3D blurring metric, of full time averaged blood flow was comparable to a conventional interleaved acquisition. The temporal resolution provided by the acceleration enabled identification and quantification of resting-state networks even in inferior regions such as the amygdala and inferior frontal lobes, where susceptibility artifacts can degrade conventional resting-state fMRI acquisitions. CONCLUSION: This approach can provide measures of blood flow modulations and resting-state networks for free within any research or clinical protocol employing ASL for resting blood flow.

Pancreatic perfusion modulation following glucose stimulation assessed by noninvasive arterial spin labeling (ASL) MRI.

BACKGROUND: More than 100 million adults in the US suffer from prediabetes or type-2 diabetes. Noninvasive imaging of pancreas endocrine function might provide a surrogate marker of ß-cell functional integrity loss linked to this disease. PURPOSE: To noninvasively assess pancreatic blood-flow modulation following a glucose challenge using arterial spin labeling (ASL) MRI. STUDY TYPE: Prospective. SUBJECTS: Fourteen adults (30 ± 7 years old, 3M/11F, body mass index [BMI] = 24 ± 3 kg.m-2 ). FIELD STRENGTH/SEQUENCE: 3T MRI / background-suppressed pseudocontinuous PCASL preparation with single-shot fast-spin-echo (FSE) readout before and after an oral glucose challenge using either fruit juice (n = 7) or over-the-counter glucose gel (n = 7). ASSESSMENT: Subjects were fasting prior to initiation of oral stimulation, then dynamic perfusion measurements were performed every 2 minutes for 30 minutes. We quantified absolute blood flow at each timepoint. STATISTICAL TESTS: Repeated-measures analysis of variance (ANOVA) followed by paired t-tests to assess for a significant effect of glucose challenge on measured perfusion. RESULTS: Measured basal blood flow was 187 ± 53 mL/100g/min. A significant blood flow increase of +38 ± 26% was observed 10 minutes poststimulation (P < 0.05) and continuing until the end of the experiment. The gel stimulation provided the most consistent results, with an early rise followed by an additional later increase consistent with the known pancreatic insulin response to elevated blood glucose. Across-subject variations in blood flow increase were partially attributable to basal flow, with a negative correlation of r = -0.84 between basal and maximal relative flow increase in the gel group. DATA CONCLUSION: ASL can be used to measure pancreatic flow in response to a glucose challenge, which could be linked to insulin release and secretion. This paradigm might be useful to characterize disorders of glucose regulation. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2020;51:854-860.

Consensus-based technical recommendations for clinical translation of renal ASL MRI.

OBJECTIVES: This study aimed at developing technical recommendations for the acquisition, processing and analysis of renal ASL data in the human kidney at 1.5 T and 3 T field strengths that can promote standardization of renal perfusion measurements and facilitate the comparability of results across scanners and in multi-centre clinical studies. METHODS: An international panel of 23 renal ASL experts followed a modified Delphi process, including on-line surveys and two in-person meetings, to formulate a series of consensus statements regarding patient preparation, hardware, acquisition protocol, analysis steps and data reporting. RESULTS: Fifty-nine statements achieved consensus, while agreement could not be reached on two statements related to patient preparation. As a default protocol, the panel recommends pseudo-continuous (PCASL) or flow-sensitive alternating inversion recovery (FAIR) labelling with a single-slice spin-echo EPI readout with background suppression and a simple but robust quantification model. DISCUSSION: This approach is considered robust and reproducible and can provide renal perfusion images of adequate quality and SNR for most applications. If extended kidney coverage is desirable, a 2D multislice readout is recommended. These recommendations are based on current available evidence and expert opinion. Nonetheless they are expected to be updated as more data become available, since the renal ASL literature is rapidly expanding.

Influence of background suppression and retrospective realignment on free-breathing renal perfusion measurement using pseudo-continuous ASL.

PURPOSE: To assess the influence of background suppression and retrospective realignment on physiological noise and image quality in free-breathing renal pseudo-continuous arterial spin labeling (pCASL). METHODS: Ten subjects were scanned at 3T with a pCASL prepared single-slice coronal acquisition through the kidneys under free breathing. Multiple acquisitions were performed with various levels of residual background signal based on optimization of pulse timings to achieve specific background suppression levels (<2%, <5%, <10%, <20%). A retrospective non-rigid motion-correction strategy was also implemented. RESULTS: Decreasing level of residual background signal was associated with higher temporal SNR. The retrospective motion-correction provided an additional but not statistically significant improvement in tSNR. The highest image quality was obtained with the lowest level of residual background signal accompanied by the retrospective motion-correction, although no significant difference in quantitative renal blood-flow could be observed. CONCLUSIONS: Renal perfusion measurement with ASL under free breathing is feasible and robust against physiological noise when using strong background suppression strategies. Finally, retrospective motion-correction further improves image quality but cannot replace background suppression.

Pancreatic perfusion and arterial-transit-time quantification using pseudocontinuous arterial spin labeling at 3T.

PURPOSE: To demonstrate the feasibility of noninvasively measuring pancreatic perfusion using pseudocontinuous arterial spin labeling (ASL) and to derive quantitative blood-flow and transit-time measurements in healthy volunteers. METHODS: A pseudocontinuous ASL sequence with background suppression and a single-slice single-shot fast-spin-echo readout was acquired at 3 T in 10 subjects with a single standard postlabeling delay (PLD) of 1.5 s and in 4 additional subjects with 4 PLD from 0.7 to 2 s. An imaging synchronized breathing approach was used to minimize motion artifacts during the 3 min of acquisition. Scan-rescan reproducibility was assessed in 3 volunteers with single-delay ASL. Quantitative blood flow and arterial transit time (ATT) were derived and the impact of ATT correction was studied using either subject-specific ATT in the second group or an average ATT derived from the group with multidelay ASL for subjects with single-delay ASL. RESULTS: Successful ASL acquisitions were performed in all volunteers. An average pancreatic blood flow of 201 ± 40 mL/100 g/min was measured in the single-delay group using an assumed ATT of 750 ms Average ATT measured in the multidelay group was 1029 ± 89 ms Using the longer, measured ATT reduced the measured flow to 162 ± 12 and 168 ± 28 mL/100 g/min with subject-specific or average ATT correction, respectively. ASL signal heterogeneities were observed at shorter PLD, potentially linked to its complex vascular supply and islet distribution. CONCLUSIONS: ASL enables reliable measurement of pancreatic perfusion in healthy volunteers. It presents a valuable alternative to contrast-enhanced methods and may be useful for diagnosis and characterization of several inflammatory, metabolic, and neoplastic diseases affecting the pancreas.

Volumetric abdominal perfusion measurement using a pseudo-randomly sampled 3D fast-spin-echo (FSE) arterial spin labeling (ASL) sequence and compressed sensing reconstruction.

PURPOSE: To improve image quality and spatial coverage for abdominal perfusion imaging by implementing an arterial spin labeling (ASL) sequence that combines variable-density 3D fast-spin-echo (FSE) with Cartesian trajectory and compressed-sensing (CS) reconstruction. METHODS: A volumetric FSE sequence was modified to include background-suppressed pseudo-continuous ASL labeling and to support variable-density (VD) Poisson-disk sampling for acceleration. We additionally explored the benefits of center oversampling and variable outer k-space sampling. Fourteen healthy volunteers were scanned on a 3T scanner to test acceleration factors as well as the various sampling schemes described under synchronized-breathing to limit motion issues. A CS reconstruction was implemented using the BART toolbox to reconstruct perfusion-weighted ASL volumes, assessing the impact of acceleration, different reconstruction, and sampling strategies on image quality. RESULTS: CS acceleration is feasible with ASL, and a strong renal perfusion signal could be observed even at very high acceleration rates (≈15). We have shown that ASL k-space complex subtraction was desirable before CS reconstruction. Although averaging of multiple highly accelerated images helped to reduce artifacts from physiologic fluctuations, superior image quality was achieved by interleaving of different highly undersampled pseudo-random spatial sampling patterns and using 4D-CS reconstruction. Combination of these enhancements produces high-quality ASL volumes in under 5 min. CONCLUSIONS: High-quality isotropic ASL abdominal perfusion volumes can be obtained in healthy volunteers with a VD-FSE and CS reconstruction. This lays the groundwork for future developments toward whole abdomen free-breathing non-contrast perfusion imaging.

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.

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.

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.

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.

Segmentation of the human spinal cord.

Segmenting the spinal cord contour is a necessary step for quantifying spinal cord atrophy in various diseases. Delineating gray matter (GM) and white matter (WM) is also useful for quantifying GM atrophy or for extracting multiparametric MRI metrics into specific WM tracts. Spinal cord segmentation in clinical research is not as developed as brain segmentation, however with the substantial improvement of MR sequences adapted to spinal cord MR investigations, the field of spinal cord MR segmentation has advanced greatly within the last decade. Segmentation techniques with variable accuracy and degree of complexity have been developed and reported in the literature. In this paper, we review some of the existing methods for cord and WM/GM segmentation, including intensity-based, surface-based, and image-based methods. We also provide recommendations for validating spinal cord segmentation techniques, as it is important to understand the intrinsic characteristics of the methods and to evaluate their performance and limitations. Lastly, we illustrate some applications in the healthy and pathological spinal cord. One conclusion of this review is that robust and automatic segmentation is clinically relevant, as it would allow for longitudinal and group studies free from user bias as well as reproducible multicentric studies in large populations, thereby helping to further our understanding of the spinal cord pathophysiology and to develop new criteria for early detection of subclinical evolution for prognosis prediction and for patient management. Another conclusion is that at the present time, no single method adequately segments the cord and its substructure in all the cases encountered (abnormal intensities, loss of contrast, deformation of the cord, etc.). A combination of different approaches is thus advised for future developments, along with the introduction of probabilistic shape models. Maturation of standardized frameworks, multiplatform availability, inclusion in large suite and data sharing would also ultimately benefit to the community.