From Phineas Gage and Monsieur Leborgne to H.M.: Revisiting Disconnection Syndromes.

On the 50th anniversary of Norman Geschwind's seminal paper entitled 'Disconnexion syndrome in animal and man', we pay tribute to his ideas by applying contemporary tractography methods to understand white matter disconnection in 3 classic cases that made history in behavioral neurology. We first documented the locus and extent of the brain lesion from the computerized tomography of Phineas Gage's skull and the magnetic resonance images of Louis Victor Leborgne's brain, Broca's first patient, and Henry Gustave Molaison. We then applied the reconstructed lesions to an atlas of white matter connections obtained from diffusion tractography of 129 healthy adults. Our results showed that in all 3 patients, disruption extended to connections projecting to areas distant from the lesion. We confirmed that the damaged tracts link areas that in contemporary neuroscience are considered functionally engaged for tasks related to emotion and decision-making (Gage), language production (Leborgne), and declarative memory (Molaison). Our findings suggest that even historic cases should be reappraised within a disconnection framework whose principles were plainly established by the associationist schools in the last 2 centuries.

Shape and volume of craniofacial cavities in intentional skull deformations.

Intentional cranial deformations (ICD) have been observed worldwide but are especially prevalent in preColombian cultures. The purpose of this study was to assess the consequences of ICD on three cranial cavities (intracranial cavity, orbits, and maxillary sinuses) and on cranial vault thickness, in order to screen for morphological changes due to the external constraints exerted by the deformation device. We acquired CT-scans for 39 deformed and 19 control skulls. We studied the thickness of the skull vault using qualitative and quantitative methods. We computed the volumes of the orbits, of the maxillary sinuses, and of the intracranial cavity using haptic-aided semi-automatic segmentation. We finally defined 3D distances and angles within orbits and maxillary sinuses based on 27 anatomical landmarks and measured these features on the 58 skulls. Our results show specific bone thickness patterns in some types of ICD, with localized thinning in regions subjected to increased pressure and thickening in other regions. Our findings confirm that volumes of the cranial cavities are not affected by ICDs but that the shapes of the orbits and of the maxillary sinuses are modified in circumferential deformations. We conclude that ICDs can modify the shape of the cranial cavities and the thickness of their walls but conserve their volumes. These results provide new insights into the morphological effects associated with ICDs and call for similar investigations in subjects with deformational plagiocephalies and craniosynostoses.

[Value of the functional neural tractography in the reconstruction of the visual pathways in DTMRI]. / Intérêt de la neurotractographie fonctionnelle dans la reconstruction des voies visuelles en IRMTD.

OBJECTIVE: This article shows that functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) are very useful in the in vivo description of the visual pathways using today's most advanced techniques and allowing fusion between fMRI and tractography. Two complementary techniques were combined: (1) DTI coupled with the tractography and (2) fMRI. MATERIALS AND METHODS: A group of 205 cases, normal and pathological, children and adults, were studied for tractographic reconstitution of visual pathways. In addition, 11 patients underwent an acquisition in fMRI (BOLD effect), with a stimulation of a black-and-white flickering checkerboard. Acquisition was carried out on a 3.0 Tesla GEHC MRI unit. Activated arrays of fMRI are overlaid with those of neurotractography (neural tractography) having like results a functional neurotractography. RESULTS AND DISCUSSION: The main components of the visual pathways were successfully reconstructed in tractography: the optic nerves, optic chiasm, optic tracts, and optic radiations. It was also possible to visualize fiber decussation within the chiasma (possible direct pathways to the hypothalamus and thalamus were also identified). CONCLUSIONS: The tensor of diffusion is increasingly used and is a promising technology to improve the diagnosis of neurological diseases. Sophisticated algorithms contribute a new vision of the anatomy, with the possibility of isolating distinct anatomical entities. With the software used, the charts of fMRI activation are overlaid on the anisotropy charts. The tractograms that link two regions of the same functional network thus provide information on subjacent structural connectivity. Consequently, one speaks about functional neurotractography.

Functional connectivity of the human red nucleus in the brain resting state at 3T.

BACKGROUND AND PURPOSE: Previous structural data obtained with diffusion tensor imaging axonal tracking have demonstrated possible in vivo connections between the human red nucleus (RN) and the sensorimotor and associative cortical areas. However, tractographic reconstructions can include false trajectories because of, for instance, the low spatial resolution of diffusion images or the inability to precisely detect fiber crossings. The rubral network was therefore reassessed by functional connectivity during the brain resting state. Because the RN is located very close to the substantia nigra (SN), the nigral network was also studied to ensure that these 2 circuits were correctly dissociated. MATERIALS AND METHODS: Data from 14 right-handed healthy volunteers were acquired at rest and analyzed by region-of-interest (ROI)-based functional connectivity. The blood oxygen level-dependent (BOLD) signal intensity fluctuations of separate ROIs located in the RN and SN were successively used to identify significant temporal correlations with BOLD signal intensity fluctuations of other brain regions. RESULTS: Low-frequency BOLD signal intensity of the RN correlated with signal intensity fluctuations in the cerebellum; mesencephalon; SN; hypothalamus; pallidum; thalamus; insula; claustrum; posterior hippocampus; precuneus; and occipital, prefrontal, and fronto-opercular cortices. Despite some cortical and subcortical overlaps with nigral connectivity, this rubral network was clearly distinct from the nigral network, which showed a strong correlation with the striatum; cerebellar vermis; and more widespread frontal, prefrontal, and orbitofrontal cortical areas. CONCLUSIONS: During the brain resting state, the human RN participates in cognitive circuits related to salience and executive control, and that may partly represent a subclass of its structural connectivity as revealed by tractography.

[The results of MRI exploration of glaucoma patients: what are the benefits?]. / Que penser des résultats d'exploration par IRM des patients atteints de glaucome?

After 13 years of glaucoma exploration using MRI at 1.5 and 3 Tesla, we have deduced that there is no specific characteristic between the different forms of this disease, which is manifested by a slowly progressing degenerative optical neuropathy, predominant from front to back (with volume of the optic nerve head always greater than the distal portions of the 2nd neurone, chiasma, and optic tract), interspersed with clinical flare-ups that are recognized by an intense localized hypersignal (frequently from the apex progressing along the canal). Visual tract involvement is always bilateral, even in cases where symptoms are exclusively unilateral (asymmetry can be observed in these cases). The discordance between (i) the severity of axon reduction and (ii) the signs of injury already present at the time when MRI is performed and the relative preservation of visual function argues for encephalic disease with visual involvement. Its delayed discovery makes treatment, even with neuroprotectors, less effective and points toward the need for implementing directed genetic prevention studies, as a first step to more effectively assessing the therapies available.

Dissociation of the neural networks recruited during a haptic object-recognition task: complementary results with a tensorial independent component analysis.

BACKGROUND AND PURPOSE: The cerebral and cerebellar networks involved in bimanual object recognition were assessed by blood oxygen level-dependent functional MR imaging by using multivariate model-free analysis, because conventional univariate model-based analysis, such as the general linear model (GLM), does not allow investigation of resting, background, and transiently task-related brain activities. MATERIALS AND METHODS: Data from 14 healthy right-handed volunteers, scanned while successively performing bilateral finger movements and a bimanual tactile-tactile matching discrimination task were analyzed by using tensor-independent component analysis (TICA), which computes statistically independent spatiotemporal processes (P > .7) thought to reflect specific and distinct anatomofunctional neural networks. These results were compared with the network obtained in a previous study by using the same paradigm based on GLM to evaluate the advantages of TICA. RESULTS: TICA characterized and distinguished the following: 1) resting-state networks such as the default-mode networks, 2) networks transiently synchronized with the beginning and end of the task, such as temporo-pericentral and temporo-pericentral-occipital networks, and 3) task-related networks such as cerebello-fronto-parietal, cerebello-prefrontocingulo-insular, and cerebello-parietal networks. CONCLUSION: Bimanual tactile-tactile matching discrimination specifically recruits a complex neural network, which can be dissociated into 3 distinct but cooperative neural subnetworks related to sensorimotor function, salience detection, executive control, and, possibly, sensory expectation. This tripartite network involved in bimanual object recognition could not be demonstrated by GLM. Moreover, TICA allowed monitoring of the temporal succession of the networks recruited during the resting phase, audition of the "go" and "stop" signals, and the tactile discrimination task.

Paul Broca's historic cases: high resolution MR imaging of the brains of Leborgne and Lelong.

In 1861, the French surgeon, Pierre Paul Broca, described two patients who had lost the ability to speak after injury to the posterior inferior frontal gyrus of the brain. Since that time, an infinite number of clinical and functional imaging studies have relied on this brain-behaviour relationship as their anchor for the localization of speech functions. Clinical studies of Broca's aphasia often assume that the deficits in these patients are due entirely to dysfunction in Broca's area, thereby attributing all aspects of the disorder to this one brain region. Moreover, functional imaging studies often rely on activation in Broca's area as verification that tasks have successfully tapped speech centres. Despite these strong assumptions, the range of locations ascribed to Broca's area varies broadly across studies. In addition, recent findings with language-impaired patients have suggested that other regions also play a role in speech production, some of which are medial to the area originally described by Broca on the lateral surface of the brain. Given the historical significance of Broca's original patients and the increasing reliance on Broca's area as a major speech centre, we thought it important to re-inspect these brains to determine the precise location of their lesions as well as other possible areas of damage. Here we describe the results of high resolution magnetic resonance imaging of the preserved brains of Broca's two historic patients. We found that both patients' lesions extended significantly into medial regions of the brain, in addition to the surface lesions observed by Broca. Results also indicate inconsistencies between the area originally identified by Broca and what is now called Broca's area, a finding with significant ramifications for both lesion and functional neuroimaging studies of this well-known brain area.

[Functional amblyopia: a functional MRI evaluation of the visual cortex response after treatment]. / Amblyopie fonctionnelle : évaluation en IRM fonctionnelle de la réponse corticale visuelle après traitement.

PURPOSE: Functional MRI evaluation of the cortical response in treated amblyopic patients. MATERIAL AND METHODS: Clinical and functional MRI exploration of ten patients, seven men and three women aged from 21 to 59 years, with strabismus management during childhood. Functional evaluations were performed on a 1.5 Tesla MR device, with four monocular functional sessions, two stimulations per eye. Alternating rest and active phases displayed still and flickering black and white checkerboards with spatial and temporal frequencies of 1 degree/8Hz and 15'/4Hz. Anatomical realignment and statistical analysis were performed using SPM99 (Statistical Parametric Mapping) to compare the four sessions in individuals. RESULTS AND DISCUSSION: In patients presenting a visual acuity of the amblyopic eye less than 0.7, stimulation of this eye induced lower response in V1, V3, and V5 in comparison with the contralateral eye stimulation. Unexpectedly, in patients recovering normal or subnormal acuity, the amblyopic eye gave comparable or enhanced response in these areas. Additional response was found in the secondary visual cortex, the cuneus, the lingual gyrus, and in parietal, frontal, and orbitofrontal areas. These results suggest a variation in cortical response depending on the efficacy of the treatment. Recovered amblyopic eye, even with acuity less than the contralateral eye, may induce a reinforced cortical sensitivity to visual stimulus. Secondary visual areas may contribute to an attentional process in image perception and analysis. Cortical plasticity may be observed several years after amblyopia treatment. CONCLUSION: Our study substantiates the importance of an effective and early treatment of functional amblyopia, inducing cortical plasticity with reinforced attention and sensitivity to visual perception.

Multi-detector row CT scanning in Paleoanthropology at various tube current settings and scanning mode.

The purpose of this study was to determine the optimal tube current setting and scanning mode for hominid fossil skull scanning, using multi-detector row computed tomography (CT). Four fossil skulls (La Ferrassie 1, Abri Pataud 1, CroMagnon 2 and Cro-Magnon 3) were examined by using the CT scanner LightSpeed 16 (General Electric Medical Systems) with varying dose per section (160, 250, and 300 mAs) and scanning mode (helical and conventional). Image quality of two-dimensional (2D) multiplanar reconstructions, three-dimensional (3D) reconstructions and native images was assessed by four reviewers using a four-point grading scale. An ANOVA (analysis of variance) model was used to compare the mean score for each sequence and the overall mean score according to the levels of the scanning parameters. Compared with helical CT (mean score=12.03), the conventional technique showed sustained poor image quality (mean score=4.17). With the helical mode, we observed a better image quality at 300 mAs than at 160 in the 3D sequences (P=0.03). Whereas in native images, a reduction in the effective tube current induced no degradation in image quality (P=0.05). Our study suggests a standardized protocol for fossil scanning with a 16 x 0.625 detector configuration, a 10 mm beam collimation, a 0.562:1 acquisition mode, a 0.625/0.4 mm slice thickness/reconstruction interval, a pitch of 5.62, 120 kV and 300 mAs especially when a 3D study is required.

[Arteriovenous malformation of the brain revealed through a visual blur and Adie's pupil]. / Tumeur vasculaire cérébrale révélée par un flou visuel concomitant à la découverte d'une pupille d'Adie.

INTRODUCTION: Arteriovenous malformations of the brain (BAVMs) are a relatively rare group involving intracranial vascular lesions (telangiectasia, cavernous malformation, venous anomaly). We report the case of a patient who presented an atypical visual symptomatology revealing a BAVM. OBSERVATION: A 48-year-old woman consulted for a recent bilateral visual blur. In darkness, discrete anisocoria appeared on the left eye. At the biomicroscopy light examination, we found areflexic semi-mydriasis (direct and consensual) on the left eye; the light reflex (direct and consensual) on the right eye was normal. During the accommodative reflex test the left pupil contracted. We propose the diagnosis of Adie's pupil, which was confirmed by the pilocarpine test (0.125%). We decided to examine the visual field because the symptomatology of the visual blur remained unexplained. The visual field showed a left homonymous inferior lateral scotoma. MRI showed a right occipital arteriovenous malformation. DISCUSSION: A quick examination could confuse painless anisocoria with a compression of the IIIrd intrinsic left nerve. This recent scotoma revealed BAVM progression. The natural history of BAVMs shows that the essential risk of these injuries is the onset of an intracranial hemorrhage. To reach a radical therapeutic decision, a cerebral arteriography clarifying the afferent and efferent vascularity of the nidus was carried out. CONCLUSION: This case is original in that it associates the concomitant discovery of a BAVM and Adie's pupil. Symptomatic BAVMs are extremely serious. Planning their treatment requires multidisciplinary cooperation in order to reduce the risk of mortality.

MR tractography with diffusion tensor imaging in clinical routine.

Using MRI, we demonstrated that the depiction of the cerebral white matter fiber tracts has become a routine procedure. Diffusion tensor (DT) sequences may be analyzed with combined volume analysis and tractography extraction software, giving indirect visualization of white matter connections. We obtained DT data from 20 subjects with normal MR imaging and five patients presenting cerebral diseases such as brain tumors, multiple sclerosis and stroke, with five patients explored on two different MR scanners. Data were transferred to dedicated workstations for anatomical realignment, determination of voxel eigenvectors and calculation of fiber tract orientations in a region of interest. In all subjects, axonal directions underlying the main neuronal pathways could be delineated. Comparisons between diseased regions and contralateral areas demonstrated changes in voxel anisotropy in injured regions, revealing possible preferential fiber orientations within diffuse T2 hyperintensities. Rapid data processing allows imaging of the normal and diseased fiber pathways as part of the routine MRI examination. Therefore, it appears that whenever white matter disease is suspected a tractography can be performed with this fast and simple method that we proved to be reliable and reproducible.

[Cortical response in age-related macular degeneration (part I). Methodology and subject specificities]. / Réponse corticale dans la DMLA (Première partie). Méthodologie et spécificités des sujets.

PURPOSE: To evaluate the cortical response to visual stimulation in patients with age-related macular degeneration (ARMD). MATERIAL AND METHODS: We conducted a prospective functional MRI study at 1.5 Testa in ten patients presenting with unilateral or bilateral ARMD and five age-matched controls. The visual stimulus was a sequence of resting phase (presentation of a fixation point on a black background) followed by an activation phase (flashes at 2 Hz). Functional data were recorded with anatomy; significant hemodynamic response secondary to neuronal activation was statistically determined using the SPM 99 software. RESULTS: The first objective was to estimate the feasibility of a functional study in the elderly. Controls and patients complained about the duration of the examination, although each of the two active functional sessions lasted only 4.5 min. The central point fixation was impaired for the patients; some deviated their gaze to center the fixation point on a perimacular retinal area. Because of substantial movement during MRI acquisitions, the data from two patients and one control were withdrawn from statistic processing. DISCUSSION AND CONCLUSION: This study is one of the few evaluations reported on functional MRI in the elderly, because of technical constraints, patient fragility and their ophthalmologic pathology. Optimizing the visual stimulus and the paradigm of stimulation, repeating patient information and support have helped demonstrate significant cortical hemodynamic response in most subjects, even in the most affected patients. Evaluation of the visual cortex by functional MRI appears feasible in the ophthalmologic pathology of the elderly, providing an adapted management of the subject's conditions.

[Cortical response to age-related macular degeneration (Part II). Functional MRI study]. / Réponse corticale dans la DMLA (Deuxième partie). Etude en IRM fonctionnelle.

UNLABELLED: PURPOSE AND MATERIALS: To evaluate the cortical response to visual stimulation in patients with age-related macular degeneration (ARMD), we conducted a functional MRI study in ten patients presenting unilateral or bilateral ARMD and five age-matched controls, using white flashes during activation phases (see Part I). RESULTS: After anatomical conformation, eight patients and four controls showed significant cortical hemodynamic response to monocular stimulations. Individual analysis was preferred to group evaluation, because of the differences in visual loss in a small number of patients. In controls, we observed cortical response in the primary visual cortex, especially at occipital poles corresponding to the macula. Patients showed a qualitative and quantitative restriction in cortical response and exclusion of occipital poles after stimulation of the affected eye, whereas activation was found in the peripheral striate and peristriate cortex. Cortical response showed hemispheric asymmetry in some patients. DISCUSSION: Our study demonstrated an activation defect in the macular projected striate cortex, corresponding to visual impairment in ARMD patients. Nevertheless, at a given visual acuity, cortical response may vary among subjects. Patients' subjective apprehension may account for such variations, as well as objective visual capacity stemming from residual functional retinal areas within the affected macula. The hemispheric asymmetry in cortical activation may result from gaze deviation onto the new fixation area in the perimacular retina, thus altering the global visual field. Enhancement in the peripheral striate and peristriate areas suggests changes in cortical interactions, possibly by a lowering of the feedback from macular projected V1. Finally, cortical evaluations must take into account degenerative phenomena delaying the hemodynamic response in the elderly. CONCLUSION: Aiming at a specific population of weakened patients with a serious visual impairment, we obtained significant results concerning cortical plasticity for visual perception in central vision deletion. Our preliminary findings must be confirmed in a larger population and correlated with other techniques exploring vision, in particular with multifocal electroretinography for retinal evaluation.

Going back to dissection in a medical curriculum: the paradigm of Necker-Enfants Malades.

In 1999, we first reported on various methods of teaching anatomy subsequent to visits to a variety of medical schools in the United States and Europe. We compared the number of contact hours for lectures, dissection classes and tutorials and provided different models for the teaching of anatomy. With respect to the nine French medical schools surveyed, it is clear that the French model is characterized by being lecture-orientated (time in lectures > time in tutorials > time spent on dissection). For the American model (also in the UK and some other parts of Europe), the training is often characterized by being dissection-based (time spent on dissection > time in lectures > time in tutorials; 10 medical schools surveyed). Exceptionally, in one Australian school, time in tutorials exceeds time in lectures (dissection = 0). The differences between the French and American models relate to teaching aims-where dissection predominates, the aims are not just the learning of anatomical facts but include practical skill acquisition and experiential learning. In 2001, to help us change the methods of teaching of anatomy in our medical school at CHU Necker-Enfants Malades (Paris V, France), we asked other French medical schools (and some foreign schools) to suggest ways of organizing anatomy training within certain time constraints. In this paper, we present the answers received. The responses received were of two kinds: (1) those providing a description of the anatomy teaching in their own medical school; (2) those providing a system for organizing the teaching if we, in Paris, have 120 hours in total to teach gross anatomy (except neuroanatomy). In the latter case, a considerable variety of different, and innovative, alternative schemes were suggested that are described in this article.

The cerebellar second homunculus remains silent during passive bimanual movements.

In a previous study, we showed that the second homunculus in lobule VIII of the cerebellum is activated during bilateral out-of-phase index finger-thumb opposition, implying a role in motor coordination. However, several recent studies indicate that the cerebellum could be more actively involved in sensory information processing during movement. Therefore, as lobule VIII activation could involve either a motor or a proprioceptive component, these two components must be distinguished and their relative contribution must be determined. Using functional imaging, we studied cerebellar activation of the same region during passively induced index finger-thumb opposition of both hands in in-phase and out-of-phase modes, thereby excluding the voluntary movement component. No significant activation was detected in lobule VIII. Intense activation of lobule VIII, obtained during active, out-of-phase bimanual movements, therefore does not involve a significant sensory component related to direct proprioceptive feedback. This result is strongly in favour of the specific recruitment of lobule VIII during out-of-phase movements related more to complex motor timing than to sensory function.

Specific neocerebellar activation during out-of-phase bimanual movements.

We used fMRI to study cerebellar activation during index finger-thumb opposition of the right hand and index finger-thumb opposition of both hands in in-phase and out-of-phase modes. The right hand movement activates the contralateral anterior lobe of the cerebellum. During bimanual in-phase movements, this activity pattern becomes bilateral. More interestingly, bilateral out-of-phase movements recruit the cerebellar posterior lobe VIII, which likely corresponds to the second homunculus. As out-of-phase movements differ from the in-phase movements only by their temporal complexity and their attentional awareness, this study demonstrates the preferential involvement of the cerebellar second homunculus in the control of complex movements.

[Tractography of the visual pathways: routine examination in magnetic resonance imaging]. / Tractographie des voies visuelles: évaluation en routine en imagerie par résonance magnétique.

Water diffusion analysis in magnetic resonance imaging (MRI) provides an elective visualization of fiber tract orientations in cerebral white matter, especially for optic tracts. We explored 25 patients from 18 to 45 years of age, with normal MRI in 20 subjects, and radiological anomalies in five. On a 1.5 Tesla MRI apparatus, diffusion tensor acquisitions were performed in 5 minutes 58 seconds with an EPI Single Shot sequence covering the entire brain. Image displacements were precluded by patient information and adequate fixation, then digitally corrected on workstations. Volume merging and fiber tract extraction were achieved using dedicated software (Volume-One and dTV). A directional depiction was obtained for all areas in the white matter, in particular for white matter junctions. Coming from the lateral geniculate body, the optic tracts were directed posteriorly toward the occipital cortex, with numerous connections to extrastriate associative areas, and through the corpus callosum and the fornix. Diffusion tractography requires optimization of volume displacements, before and secondary to MRI acquisitions. Our diffusion tensor acquisition, with image optimization in a short-duration sequence can be routinely applied to all patients, for a specific analysis of functional connections between cortical areas of cerebral white matter.

[Acute optic neuritis: clinical and MRI prognostic factors. Study of fifty patients]. / Neuropathie optique inflammatoire aiguë: facteurs pronostiques cliniques et IRM.

The objective of this study was to evaluate the risk of visual outcome after acute optic neuritis (ON) in relation to clinical and MRI findings. Fifty cases of acute ON within one month were retrospectively studied. MRI with Short Tau Inversion Recovery (STIR) sequence of the optic nerve were obtained with a median time onset of 9 days after ON. Mean age of patients was 32.8 years, mean initial visual acuity was 3/10 and orbital pain was present in 86 percent100 of patients. The STIR sequence revealed lesion in 88 percent 100 of acutely symptomatic optic nerves. An initial low visual acuity (less than 2/10), the absence of orbital pain and involvement of the intracanalicular portion of the optic nerve on STIR sequence were statistically correlated with a poorer visual outcome (respectively p=0.0041, p=0.035 and p=0.011).

Correlating multiple MRI parameters with clinical features: an attempt to define a new strategy in multiple sclerosis.

MRI is the most powerful imaging technique in managing patients with suspected or confirmed multiple sclerosis (MS). However, conventional MRI variables show nonspecific abnormalities weakly correlated with clinical progression of the disease. New techniques, now routinely available, offer better characterisation of the pathophysiology. We combined conventional MRI, including lesion load, contrast enhancement and "black holes" with magnetisation transfer and diffusion-weighted imaging and localised proton MR spectroscopy (MRS) to study their relationship with disability, course and duration of MS. The variables that were the most significantly linked to the course of the disease (relapsing remitting versus secondary progressive) were lesion load, mean overall magnetisation transfer ratio and apparent diffusion coefficient (MGADC), the percentage of ADC in (PADCIMD), and out of (PAD-COMD) modal distribution, and the ratio N-acetylaspartate and creatine-containing compounds on MRS of the centrum semiovale. MGADC and PADCIMD were the independent factors most related to disability and duration of disease. Combining MRI techniques is clinically relevant and feasible for studies of MS and may be applied to other diseases of the central nervous system.