Manuel Taso

Framework for integrated MRI average of the spinal cord white and gray matter: The MNI-Poly-AMU template

The field of spinal cord MRI is lacking a common template, as existing for the brain, which would allow extraction of multi-parametric data (diffusion-weighted, magnetization transfer, etc.) without user bias, thereby facilitating group analysis and multi-center studies. This paper describes a framework to produce an unbiased average anatomical template of the human spinal cord. The template was created by co-registering T2-weighted images (N = 16 healthy volunteers) using a series of pre-processing steps followed by non-linear registration. A white and gray matter probabilistic template was then merged to the average anatomical template, yielding the MNI-Poly-AMU template, which currently covers vertebral levels C1 to T6. New subjects can be registered to the template using a dedicated image processing pipeline. Validation was conducted on 16 additional subjects by comparing an automatic template-based segmentation and manual segmentation, yielding a median Dice coefficient of 0.89. The registration pipeline is rapid (~15 min), automatic after one C2/C3 landmark manual identification, and robust, thereby reducing subjective variability and bias associated with manual segmentation. The template can notably be used for measurements of spinal cord cross-sectional area, voxel-based morphometry, identification of anatomical features (e.g., vertebral levels, white and gray matter location) and unbiased extraction of multi-parametric data.

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.

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.

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

Abstract 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 Symbol‐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. Symbol. No caption available. Graphical abstract Figure. No Caption available. HighlightsAutomatic segmentation of the spinal cord white/gray matter in various MRI contrasts.Robust white/gray matter segmentation in patients with spinal cord injury.Vertebral level information as a shape prior for white/gray matter segmentation.Improved template‐based analysis framework that accounts for gray matter shape.

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.

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

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.

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.

NON-INVASIVE IMAGING OF CHOROID PLEXUS BLOOD FLOW AND ITS POTENTIAL RELATIONSHIP TO CSF GENERATION

cerebral hemodynamics related to the task in non-invasive and unconstrained manners. The purpose of this study is to establish the novel index to monitor cognitive function using fNIRS in the daily function levels in healthy elderly, pre-clinical AD and MCI subjects. Methods:The observation study between non-dementia control (NDC) and MCI was approved by site Institutional Review Boards with written informed consent. The inclusion and exclusion criteria of NDC or MCI were basically referred to the Alzheimer’s Disease Neuroimaging Protocol (ADNI). Cerebral hemodynamics signals were acquired at total 54 channels to cover the cortex region of not only forehead but parietal and somatosensory area on agematched 14 NDC and 12 MCI subjects using continuous-wave fNIRS system by the single daily function level task developed by us. fNIRS signals were refined with principal component analysis spatial filtering to remove global components, then linear regression model between NDC and MCI in combination with all feature quantity of fNIRS signals was obtained using the least absolute shrinkage and selection operator (LASSO) analysis. The receiver operation characteristic (ROC) analysis was done to evaluate the clinical usefulness of the linear regressionmodel which can calculate cognitive ability index. Accuracy of this new index was evaluated using another 25 test data (17 NDC and 8 MCI). Results: The combination of feature quantity; Deoxy-Hb and signal area by sensory examination task showed good consensus to correlate with the region-of-interest on cerebral cortex as well as good performance with an area under the curve (AUC) 0.99, sensitivity 100% and specificity 93% in NDC vs MCI. Accuracy of 25 test data was 58%. Conclusions: fNIRS approach to get the index for cognitive function in present study is potential to monitor the cognitive-normal brain activity in the daily function levels.