Identification and measurement of cervical spinal cord atrophy in neuromyelitis optica spectrum disorders (NMOSD) and correlation with clinical characteristics and cervical spinal cord MRI data.

INTRODUCTION: The spinal cord is one of the two main targets of neuromyelitis optica (NMO). The aim of this study was to highlight cervical spinal cord atrophy in NMO patients as compared to controls and to assess correlations between atrophy and clinical characteristics and cervical spinal cord MRI data. METHODS: This prospective study investigated 15 patients with a diagnosis of NMOSD and 15 healthy controls. The whole cervical spinal cord was explored by MRI. The cross-sectional area (CSA) was estimate at every level of cup. This measurement was then averaged on the whole cervical spinal cord, providing a single measurement for every subject, denoted as mean CSA. RESULTS: Mean CSA was 68.5 mm2 in the population of NMO patients and 72.8 mm2 in the population of healthy subjects. NMO patients had significantly smaller cervical spinal cord area than healthy controls (T test=0.009). Cervical spinal cord atrophy was associated with clinical signs of medullary involvement (T test=0.0006). There was a tendency toward a relation between cervical spinal cord atrophy and the Expanded Disability Status Scale (EDSS) (T test=0.07). This correlation seems statistically significant (T test<0.05) at the level of the upper cervical spinal cord (C2-C3) CONCLUSION: This study provides the first evidence of cervical spinal cord atrophy in NMOSD by studying the entire cervical spinal cord. Upper cervical spinal cord atrophy was substantially correlated to clinical disability and seems more involved in the development of clinical disability in NMOSD patients in comparison to the lower cervical spinal cord.

T1- or T2-weighted magnetic resonance imaging: what is the best choice to evaluate atrophy of the hippocampus?

BACKGROUND AND PURPOSE: Magnetic resonance imaging is part of the diagnostic criteria for Alzheimer's disease (AD) through the evaluation of hippocampal atrophy. The objective of this study was to evaluate which sequence of T1-weighted (T1WI) and T2-weighted (T2WI) imaging allowed the best visual evaluation of hippocampal atrophy. METHODS: Visual qualitative ratings of the hippocampus of 100 patients with mild cognitive impairment (MCI) and 50 patients with AD were made independently by four operators according to the medial temporal lobe atrophy score based either on T1WI or T2WI. These two evaluations were compared in terms of interobserver reproducibility, concordance with a quantitative volumetric measure, discrimination power between AD and MCI groups, and correlation with several neuropsychological tests. RESULTS: The medial temporal lobe atrophy score evaluated on either T1WI or T2WI exhibited similar interobserver variability and accordance with quantitative volumetric evaluation. However, the visual evaluation on T2WI seemed to provide better discrimination power between AD and MCI groups for both left (T1WI, P = 0.0001; T2WI, P = 7.072 × 10-5 ) and right (T1WI, P = 0.008; T2WI, P = 0.001) hippocampus, and a higher overall correlation with neuropsychological tests. CONCLUSIONS: The present study suggests that T2WI provides a more adequate visual rating of hippocampal atrophy.

Exploring anterograde memory: a volumetric MRI study in patients with mild cognitive impairment.

BACKGROUND: The aim of this volumetric study was to explore the neuroanatomical correlates of the Free and Cued Selective Reminding Test (FCSRT) and the Delayed Matching-to-Sample-48 items (DMS-48), two tests widely used in France to assess verbal and visual anterograde memory. We wanted to determine to what extent the two tests rely on the medial temporal lobe, and could therefore be predictive of Alzheimer's disease, in which pathological changes typically start in this region. METHODS: We analysed data from a cohort of 138 patients with mild cognitive impairment participating in a longitudinal multicentre clinical research study. Verbal memory was assessed using the FCSRT and visual recognition memory was evaluated using the DMS-48. Performances on these two tests were correlated to local grey matter atrophy via structural MRI using voxel-based morphometry. RESULTS: Our results confirm the existence of a positive correlation between the volume of the medial temporal lobe and the performance on the FCSRT, prominently on the left, and the performance on the DMS-48, on the right, for the whole group of patients (family-wise error, P < 0.05). Interestingly, this region remained implicated only in the subgroup of patients who had deficient scores on the cued recall of the FCSRT, whereas the free recall was associated with prefrontal aspects. For the DMS-48, it was only implicated for the group of patients whose performances declined between the immediate and delayed trial. Conversely, temporo-parietal cortices were implicated when no decline was observed. Within the medial temporal lobe, the parahippocampal gyrus was prominently involved for the FCSRT and the immediate trial of the DMS-48, whereas the hippocampus was solely involved for the delayed trial of the DMS-48. CONCLUSIONS: The two tests are able to detect an amnestic profile of the medial temporal type, under the condition that the scores remain deficient after the cued recall of the FCSRT or decline on the delayed recognition trial of the DMS-48. Strategic retrieval as well as perceptual/attentional processes, supported by prefrontal and temporo-parietal cortices, were also found to have an impact on the performances. Finally, the implication of the hippocampus appears time dependent, triggered by a longer delay than the parahippocampus, rather than determined by the sense of recollection or the encoding strength associated with the memory trace.

Value of MRI olfactory bulb evaluation in the assessment of olfactory dysfunction in Bardet-Biedl syndrome.

Olfactory bulb (OB) volume evaluation by magnetic resonance imaging (MRI) has been demonstrated to be related to olfactory dysfunction in many different diseases. Olfactory dysfunction is often overlooked in Bardet-Biedl syndrome (BBS) patients and is rarely objectively evaluated by MRI. We present a series of 20 BBS patients with olfactory dysfunction. The OB was evaluated separately and blindly by two radiologists (SR and SM) with 3 Tesla MRI imaging comparatively to 12 normal control subjects by global visual evaluation and by quantitative measurement of OB volume. In the 12 control cases OB visual evaluation was considered as normal in all cases for radiologist (SR) and in 10 cases for radiologist (SM). In the 20 BBS patients, OB visual evaluation was considered as abnormal in 18 cases for SR and in all cases for SM. OB volumetric evaluation for SR and SM in BBS patients was able to provide significant correlation between BBS and olfactory dysfunction. This study indicates that OB volume evaluation by MRI imaging like structural MRI scan for gray matter modifications demonstrates that olfactory dysfunction in BBS patients is a constant and cardinal symptom integrated in a genetical syndrome with peripheral and central olfactory structure alterations.

Distinct and common cerebral activation changes during mental time travel in relapsing-remitting multiple sclerosis patients.

Mental time travel (MTT) entails the ability to mentally travel into autobiographical memory (AM) and episodic future thinking (EFT). While AM and EFT share common phenomenological and cerebral functional properties, distinctive characteristics have been documented in healthy and clinical populations. No report, to our knowledge, has informed on the functional underpinnings of MTT impairment in multiple sclerosis (MS) patients, hence the aim of this work. We studied 22 relapsing-remitting MS patients and 22 matched controls. Participants underwent an AM/EFT assessment using the Autobiographical Interview (Levine et al. 2002), followed by a functional MRI session. The latter consisted in AM and EFT tasks, distinguishing the construction and elaboration phases of events. The results showed impaired performance for AM and EFT in patients, accompanied by increased cerebral activations mostly located in the frontal regions, which extended to the parietal, lateral temporal and posterior regions during AM/EFT tasks, relative to healthy controls. Enhanced brain activations in MS patients were particularly evident during the EFT task and involved the hippocampus, frontal, external temporal, and cingulate regions. The construction phase required greater fronto-parieto-temporal activations in MS patients relative to both healthy controls, and the elaboration phase. Taking together, our results suggested the occurrence of cerebral activation changes in the context of MTT in MS patients, expressed by distinct and common mechanisms for AM and EFT. This study may provide new insights in terms of cerebral activation changes in brain lesion and their application to clinical settings, considering AM/EFT's central role in everyday life.

Olfaction evaluation and correlation with brain atrophy in Bardet-Biedl syndrome.

Bardet-Biedl syndrome (BBS) is a well-recognized ciliopathy characterized by cardinal features namely: early onset retinitis pigmentosa, polydactyly, obesity, hypogonadism, renal and cognitive impairment. Recently, disorders of olfaction (anosmia, hyposmia) have been also described in BBS patients. Moreover, morphological brain anomalies have been reported and prompt for further investigations to determine whether they are primary or secondary to peripheral organ involvement (i.e. visual or olfactory neuronal tissue). The objective of this article is to evaluate olfactory disorders in BBS patients and to investigate putative correlation with morphological cerebral anomalies. To this end, 20 BBS patients were recruited and evaluated for olfaction using the University of Pennsylvania Smell Identification Test (UPSIT). All of them underwent a structural magnetic resonance imaging (MRI) scan. We first investigated brain morphological differences between BBS subjects and 14 healthy volunteers. Then, we showed objective olfaction disorders in BBS patients and highlight correlation between gray matter volume reduction and olfaction dysfunction in several brain areas.

Evaluation of brain atrophy estimation algorithms using simulated ground-truth data.

A number of analysis tools have been developed for the estimation of brain atrophy using MRI. Since brain atrophy is being increasingly used as a marker of disease progression in many neuro-degenerative diseases such as Multiple Sclerosis and Alzheimer's disease, the validation of these tools is an important task. However, this is complex, in the real scenario, due to the absence of gold standards for comparison. In order to create gold standards, we first propose an approach for the realistic simulation of brain tissue loss that relies on the estimation of a topology preserving B-spline based deformation fields. Using these gold standards, an evaluation of the performance of three standard brain atrophy estimation methods (SIENA, SIENAX and BSI-UCD), on the basis of their robustness to various sources of error (bias-field inhomogeneity, noise, geometrical distortions, interpolation artefacts and presence of lesions), is presented. Our evaluation shows that, in general, bias-field inhomogeneity and noise lead to larger errors in the estimated atrophy than geometrical distortions and interpolation artefacts. Experiments on 18 different anatomical models of the brain after simulating whole brain atrophies in the range of 0.2-1.5% indicate that, in the presence of bias-field inhomogeneity and noise, a mean error of 0.64+/-0.53%,4.00+/-2.41% and 1.79+/-0.97% may be expected in the atrophy estimated by SIENA, SIENAX and BSI-UCD, respectively.

Retrospective evaluation of a topology preserving non-rigid registration method.

This paper proposes a comprehensive evaluation of a monomodal B-spline-based non-rigid registration algorithm allowing topology preservation in 3-D. This article is to be considered as the companion of [Noblet, V., Heinrich, C., Heitz, F., Armspach, J.-P., 2005. 3-D deformable image registration: a topology preservation scheme based on hierarchical deformation models and interval analysis optimization. IEEE Transactions on Image Processing, 14 (5), 553-566] where this algorithm, based on the minimization of an objective function, was introduced and detailed. Overall assessment is based on the estimation of synthetic deformation fields, on average brain construction, on atlas-based segmentation and on landmark mapping. The influence of the model parameters is characterized. Comparison between several objective functions is carried out and impact of their symmetrization is pointed out. An original intensity normalization scheme is also introduced, leading to significant improvements of the registration quality. The comparison benchmark is the popular demons algorithm [Thirion, J.-P., 1998. Image matching as a diffusion process: an analogy with Maxwell's demons. Medical Image Analysis, 2 (3), 243-260], that exhibited best results in a recent comparison between several non-rigid 3-D registration methods [Hellier, P., Barillot, C., Corouge, I., Gibaud, B., Le Goualher, G., Collins, D.L., Evans, A., Malandain, G., Ayache, N., Christensen, G.E., Johnson, H.J., 2003. Retrospective evaluation of intersubject brain registration. IEEE Transactions on Medical Imaging, 22 (9), 1120-1130]. The topology preserving B-spline-based method proved to outperform the commonly available ITK implementation of the demons algorithms on many points. Some limits of intensity-based registration methods are also highlighted through this work.