[Role of tractography in stereotactic radiosurgery and brain stereotactic radiotherapy]. / Intérêt de la tractographie pour la radiochirurgie et la radiothérapie stéréotaxique cérébrale.

Hypofractionated stereotactic radiotherapy and stereotactic radiosurgery are major therapeutic weapons in the brain, whether for tumor, vascular or functional treatments. They tend increasingly to democratize and to become standard treatments. However, human brain anatomy is very complex and not limited to the currently described organs at risk. Diffusion tensor imaging (DTI) tractography is a simple tool that enables to identify reproducibly big white matter fiber tracts. Not only does tractography allow a redefinition of organs at risk in the brain, but it would also allow the identification of new targets, such as the ventral intermediate nucleus (Vim) within the thalamus for treatment of movement disorders. We present here a review of the role of tractography and the anatomy, function and currently described dose-effect relationships of white matter fiber tracts with a major functional impact: the pyramidal tract for motor ability, the optic radiation for vision and the arcuate fasciculus for language.

The neural correlates of the visual consciousness in schizophrenia: an fMRI study.

In the current literature, two distinct and opposite models are suggested to explain the consciousness disorders in schizophrenia. The first one suggests that consciousness disorders rely on a low-level processing deficit, when the second model suggests that consciousness disorders rely on disruption in the ability to consciously access information, with preserved unconscious processing. The current study aims to understand the mechanisms associated with visual consciousness disorder in order to pave the road that will settle the debate regarding these hypotheses. During a functional magnetic resonance imaging session, 19 healthy participants (HC) and 15 patients with schizophrenia (SCZ) performed a visual detection task to compare the neural substrates associated with the conscious access to the visual inputs. The visual detection threshold was significantly higher in SCZ than in HC [t(32) = 3.37, p = 0.002]. Whole-brain ANOVA demonstrated that around the visual detection threshold patients with SCZ failed to activate a large network of brain areas compared to HC. (1) During conscious vision, HC engaged more the left cuneus and the right occipital cortex than patients with SCZ, (2) during unconscious vision, HC engaged a large network that patients with SCZ failed to activate, and finally, (3) during the access to consciousness process, patients with SCZ failed to activate the anterior cingulate cortex. These results suggest that the consciousness disorders in schizophrenia rely on specific dysfunctions depending on the consciousness stage. The disorders of the conscious vision are associated with dysfunction of occipital areas while the ones associated with unconscious vision rely on a large widespread network. Finally, the conscious access to the visual inputs is impaired by a dysfunction of the anterior cingulate cortex. The current study suggests that none of the two suggested models can explain consciousness disorders in schizophrenia. We suggest that there is an alternative model supporting that the conscious access to visual inputs is due to a disengagement of the supragenual anterior cingulate during the unconscious processing of the visual inputs associated with a sensory deficit.

Anatomo-radiological correlation between diffusion tensor imaging and histologic analyses of glial tumors: a preliminary study.

BACKGROUND AND PURPOSE: The challenge of the neurosurgical management of gliomas lies in achieving a maximal resection without persistent functional deficit. Diffusion tensor imaging (DTI) allows non-invasive identification of white matter tracts and their interactions with the tumor. Previous DTI validation studies were compared with intraoperative cortical stimulation, but none was performed based on the tumor anatomopathological analysis. This preliminary study evaluates the correlation between the preoperative subcortical DTI tractography and histology in terms of fiber direction as well as potential tumor-related fiber disruption. METHODS: Eleven patients harboring glial tumors underwent preoperative DTI images. Correlations were performed between the visual color-coded anisotropy (FA) map analysis and the tumor histology after "en bloc" resection. Thirty-one tumor areas were classified according to the degree of tumor infiltration, the destruction of myelin fibers and neurofilaments, the presence of organized white matter fibers, and their orientation in space. RESULTS: After histologic comparison, the DTI sensitivity and specificity to predict disrupted fiber tracts were respectively of 89% and 90%. The positive and negative predicted values of DTI were 80% and 95%. The DTI data were in line with the histologic myelin fiber orientation in 90% of patients. In our series, the prevalence of destructed fiber was 31%. Glioblastoma WHO grade IV harbored a higher proportion of destructed white matter tracts. Lower WHO grades were associated with higher preservation of subcortical fiber tracts. CONCLUSION: This DTI/histology study of "en bloc"-resected gliomas reported a high and reproducible concordance of the visual color-coded FA map with the histologic examination to predict subcortical fiber tract disruption. Our series brought consistency to the DTI data that could be performed routinely for glioma surgery to predict the tumor grade and the postoperative clinical outcomes.

High-field intraoperative MRI in glioma surgery: A prospective study with volumetric analysis of extent of resection and functional outcome.

BACKGROUND: High-field intraoperative MRI (IoMRI) is a useful tool to improve the extent of glioma resection (EOR). OBJECTIVE: To compare the interest of 1.5T IoMRI in glioma surgery between enhancing and non-enhancing tumors, based on volumetric analysis. METHODS: A prospective single-center study included consecutive adult patients undergoing glioma surgery with IoMRI. Volumetric evaluation was based on FLAIR hypersignal after gadolinium injection in non-enhancing tumors and T1 hypersignal after gadolinium injection in enhancing tumors. Endpoints comprised: residual tumor volume (RTV), EOR, workflow and clinical outcome on Karnofsky performance score (KPS). RESULTS: Fifty-three surgeries were performed from July 2014 to January 2016. Thirty-four patients underwent one IoMRI, and 19 two IoMRIs. In non-enhancing tumors, intraoperative RTV on 1st IoMRI T2/FLAIR was higher than in enhancing tumors on T1 sequences (7.25cm3 vs. 0.74cm3, respectively; P=0.008), whereas the RTV on 2nd IoMRIs and final RTV were no longer significantly different. After IoMRI, 72% of patients underwent additional resection. In non-enhancing tumors, EOR increased from 77.3% on 1st IoMRI to 97.4% on last MRI (P<0.001). Taking all tumors together, final RTV values were: median=0cm3, mean=3.9cm3. Mean final EOR was 94%. In 25% of patients, KPS was reduced during early postoperative course; at 3 and 6 months postoperatively, median KPS was 90. CONCLUSION: Intraoperative MRI guidance significantly enhanced the extent of glioma resection, especially for non- or minimally enhancing tumors, while preserving patient autonomy.

Hippocampal Deformations and Entorhinal Cortex Atrophy as an Anatomical Signature of Long-Term Cognitive Impairment: from the MCAO Rat Model to the Stroke Patient.

Stroke patients have an elevated risk of developing long-term cognitive disorders or dementia. The latter is often associated with atrophy of the medial temporal lobe. However, it is not clear whether hippocampal and entorhinal cortex atrophy is the sole predictor of long-term post-stroke dementia. We hypothesized that hippocampal deformation (rather than atrophy) is a predictive marker of long-term post-stroke dementia on a rat model and tested this hypothesis in a prospective cohort of stroke patients.Male Wistar rats were subjected to transient middle cerebral artery occlusion and assessed 6 months later. Ninety initially dementia-free patients having suffered a first-ever ischemic stroke were prospectively included in a clinical study. In the rat model, significant impairments in hippocampus-dependent memories were observed. MRI studies did not reveal significant atrophy of the hippocampus volume, but significant deformations were indeed observed-particularly on the ipsilateral side. There, the neuronal surface area was significantly lower in ischemic rats and was associated with a lower tissue density and a markedly thinner entorhinal cortex. At 6 months post-stroke, 49 of the 90 patients displayed cognitive impairment (males 55.10%). Shape analysis revealed marked deformations of their left hippocampus, a significantly lower entorhinal cortex surface area, and a wider rhinal sulcus but no hippocampal atrophy. Hence, hippocampal deformations and entorhinal cortex atrophy were associated with long-term impaired cognitive abilities in a stroke rat model and in stroke patients. When combined with existing biomarkers, these markers might constitute sensitive new tools for the early prediction of post-stroke dementia.

Intraoperative MRI for the management of brain lesions adjacent to eloquent areas.

BACKGROUND: The aim of our study was to report the usefulness of intraoperative MRI guidance in the resection of brain lesions adjacent to eloquent areas. PATIENTS AND METHODS: A single center prospective series of gliomas amenable to optimized resection with intraoperative MRI between September 2014 and December 2015. RESULTS: The study included 56 patients. The median duration of the first intraoperative MRI was 38min, interquartile range (IQR 30-46). Fourteen patients (40%) underwent a second intraoperative MRI, which had a median duration of 26min (IQR, 18-30). The median total operative time was 265min (IQR, 242-337). After the first intraoperative MRI, the median residual glioma volume of the 35 gliomas adjacent to eloquent areas was 7.04cm3 (IQR, 2.22-13.8), which did not significantly differ from the other gliomas (P=0.07). After the second intraoperative MRI, the median residual glioma volume was 3.86cm3 (IQR, 0.82-6.99), which did not significantly differ from the other patients (P=0.700). On the postoperative MRI, the median extent of the glioma resections adjacent to eloquent areas was 99.78% (IQR, 88.9-100), which was not significantly different from the rest of the population (P=0.290). At 6 months after surgery, the median Karnofsky Performance Score was 90, and 2.8% of the patients presented a permanent new neurological deficit. CONCLUSION: Our results suggest that intraoperative MRI is an effective and safe technique to improve the extent of brain lesion resections close to eloquent areas.

The value of magnetic resonance imaging as a biomarker for amyotrophic lateral sclerosis: a systematic review.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a fatal, rapidly progressive neurodegenerative disease that mainly affects the motor system. A number of potentially neuroprotective and neurorestorative disease-modifying drugs are currently in clinical development. At present, the evaluation of a drug's clinical efficacy in ALS is based on the ALS Functional Rating Scale Revised, motor tests and survival. However, these endpoints are general, variable and late-stage measures of the ALS disease process and thus require the long-term assessment of large cohorts. Hence, there is a need for more sensitive radiological biomarkers. Various sequences for magnetic resonance imaging (MRI) of the brain and spinal cord have may have value as surrogate biomarkers for use in future clinical trials. Here, we review the MRI findings in ALS, their clinical correlations, and their limitations and potential role as biomarkers. METHODS: The PubMed database was screened to identify studies using MRI in ALS. We included general MRI studies with a control group and an ALS group and longitudinal studies even if a control group was lacking. RESULTS: A total of 116 studies were analysed with MRI data and clinical correlations. The most disease-sensitive MRI patterns are in motor regions but the brain is more broadly affected. CONCLUSION: Despite the existing MRI biomarkers, there is a need for large cohorts with long term MRI and clinical follow-up. MRI assessment could be improved by standardized MRI protocols with multicentre studies.

[Brain metastases imaging]. / Imagerie des métastases cérébrales.

The therapeutic management of brain metastases depends upon their diagnosis and characteristics. It is therefore imperative that imaging provides accurate diagnosis, identification, size and localization information of intracranial lesions in patients with presumed cerebral metastatic disease. MRI exhibits superior sensitivity to CT for small lesions identification and to evaluate their precise anatomical location. The CT-scan will be made only in case of MRI's contraindication or if MRI cannot be obtained in an acceptable delay for the management of the patient. In clinical practice, the radiologic metastasis evaluation is based on visual image analyses. Thus, a particular attention is paid to the imaging protocol with the aim to optimize the diagnosis of small lesions and to evaluate their evolution. The MRI protocol must include: 1) non-contrast T1, 2) diffusion, 3) T2* or susceptibility-weighted imaging, 4) dynamic susceptibility contrast perfusion, 5) FLAIR with contrast injection, 6) T1 with contrast injection preferentially using the 3D spin echo images. The role of the nuclear medicine imaging is still limited in the diagnosis of brain metastasis. The Tc-sestamibi brain imaging or PET with amino acid tracers can differentiate local brain metastasis recurrence from radionecrosis but still to be evaluated.

Deafferentation in thalamic and pontine areas in severe traumatic brain injury.

PURPOSE: Severe traumatic brain injury (TBI) is characterized mainly by diffuse axonal injuries (DAI). The cortico-subcortical disconnections induced by such fiber disruption play a central role in consciousness recovery. We hypothesized that these cortico-subcortical deafferentations inferred from diffusion MRI data could differentiate between TBI patients with favorable or unfavorable (death, vegetative state, or minimally conscious state) outcome one year after injury. METHODS: Cortico-subcortical fiber density maps were derived by using probabilistic tractography from diffusion tensor imaging data acquired in 24 severe TBI patients and 9 healthy controls. These maps were compared between patients and controls as well as between patients with favorable (FO) and unfavorable (UFO) 1-year outcome to identify the thalamo-cortical and ponto-thalamo-cortical pathways involved in the maintenance of consciousness. RESULTS: Thalamo-cortical and ponto-thalamo-cortical fiber density was significantly lower in TBI patients than in healthy controls. Comparing FO and UFO TBI patients showed thalamo-cortical deafferentation associated with unfavorable outcome for projections from ventral posterior and intermediate thalamic nuclei to the associative frontal, sensorimotor and associative temporal cortices. Specific ponto-thalamic deafferentation in projections from the upper dorsal pons (including the reticular formation) was also associated with unfavorable outcome. CONCLUSION: Fiber density of cortico-subcortical pathways as measured from diffusion MRI tractography is a relevant candidate biomarker for early prediction of one-year favorable outcome in severe TBI.

The value of novel MRI techniques in Parkinson-plus syndromes: diffusion tensor imaging and anatomical connectivity studies.

Conventional MRI is a well-described, highly useful tool for the differential diagnosis of degenerative parkinsonian syndromes. Nevertheless, the observed abnormalities may only appear in late-stage disease. Diffusion tensor imaging (DTI) can identify microstructural changes in brain tissue integrity and connectivity. The technique has proven value in the differential diagnosis of multiple system atrophy (MSA), progressive supranuclear palsy (PSP) and Parkinson's disease (PD). Here, we performed a systematic review of the literature on the main corticosubcortical DTI abnormalities identified to date in the context of the diagnosis of MSA and PSP with diffusion-weighted imaging, diffusion tensor imaging and anatomical connectivity studies. In good agreement with the histological data, increased diffusivity in the putamen (in MSA and PSP), in the middle cerebellar peduncles (in MSA) and in the upper cerebellar peduncles (in PSP) has been reported. Motor pathway involvement is characterized by low fraction anisotropy (FA) in the primary motor cortex in MSA-P and PSP, a high apparent diffusion coefficient (ADC) and low FA in the supplementary motor area in PSP. We then outline the value of these techniques in differential diagnosis (especially with respect to PD). Anatomical connectivity studies have revealed a lower number of fibers in the corticospinal tract in MSA and PSP (relative to PD and controls) and fewer tracked cortical projection fibers in patients with PSP or late-stage MSA (relative to patients with early MSA or PD and controls). Lastly, we report the main literature data concerning the value of DTI parameters in monitoring disease progression. The observed correlations between DTI parameters on one hand and clinical scores and/or disease duration on the other constitute strong evidence of the value of DTI in monitoring disease progression. In MSA, the ataxia score was correlated with ADC values in the pons and the upper cerebellar peduncles, whereas both the motor score and the disease duration were correlated with putaminal ADC values. In conclusion, DTI and connectivity studies constitute promising tools for differentiating between "Parkinson-plus" syndromes.

Connectivity between right inferior frontal gyrus and supplementary motor area predicts after-effects of right frontal cathodal tDCS on picture naming speed.

BACKGROUND: Cathodal transcranial direct current stimulation (tDCS) of the right frontal cortex improves language abilities in post-stroke aphasic patients. Yet little is known about the effects of right frontal cathodal tDCS on normal language function. OBJECTIVE/HYPOTHESIS: To explore the cathodal tDCS effects of the right-hemispheric homologue of Broca's area on picture naming in healthy individuals. We hypothesized that cathodal tDCS improves picture naming and that this effect is determined by the anatomical and functional connectivity of the targeted region. METHODS: Cathodal and sham tDCS were applied to the right inferior frontal gyrus in 24 healthy subjects before a picture-naming task. All participants were studied with magnetic resonance imaging at pre-interventional baseline. Probabilistic tractography and dynamic causal modeling of functional brain activity during a word repetition task were applied to characterize anatomical and functional connectivity. RESULTS: Subjects named pictures faster after cathodal relative to sham tDCS. The accelerating effect of tDCS was explained by a reduced frequency of very slow responses. tDCS-induced acceleration of picture naming correlated with larger volumes of the tract connecting the right Broca's area and the supplementary motor area (SMA) and greater functional coupling from the right SMA to the right Broca's area. CONCLUSIONS: The results support the notion that the after-effects of tDCS on brain function are at least in part determined by the anatomical and functional connectivity of the targeted region.

The multimodal connectivity of the hippocampal complex in auditory and visual hallucinations.

Hallucinations constitute one of the most representative and disabling symptoms of schizophrenia. Several Magnetic Resonance Imaging (MRI) findings support the hypothesis that distinct patterns of connectivity, particularly within networks involving the hippocampal complex (HC), could be associated with different hallucinatory modalities. The aim of this study was to investigate HC connectivity as a function of the hallucinatory modality, that is, auditory or visual. Two carefully selected subgroups of schizophrenia patients with only auditory hallucinations (AH) or with audio-visual hallucinations (A+VH) were compared using the following three complementary multimodal MRI methods: resting state functional MRI, diffusion MRI and structural MRI were used to analyze seed-based Functional Connectivity (sb-FC), Tract-Based Spatial Statistics (TBSS) and shape analysis, respectively. Sb-FC was significantly higher between the HC, the medial prefrontal cortex (mPFC) and the caudate nuclei in A+VH patients compared with the AH group. Conversely, AH patients exhibited a higher sb-FC between the HC and the thalamus in comparison with the A+VH group. In the A+VH group, TBSS showed specific higher white matter connectivity in the pathways connecting the HC with visual areas, such as the forceps major and the inferior-fronto-occipital fasciculus than in the AH group. Finally, shape analysis showed localized hippocampal hypertrophy in the A+VH group. Functional results support the fronto-limbic dysconnectivity hypothesis of schizophrenia, while specific structural findings indicate that plastic changes are associated with hallucinations. Together, these results suggest that there are distinct connectivity patterns in patients with schizophrenia that depend on the sensory-modality, with specific involvement of the HC in visual hallucinations.

[Imaging of lateral ventricle tumors]. / Imagerie des tumeurs du ventricule latéral.

Lateral ventricular neoplasms are rare, and account for 50% of all intraventricular tumors in adults and 25% in children. Although these neoplasms are easily detected with computed tomography (CT) and magnetic resonance imaging (MRI), both techniques are relatively unspecific in identifying the type of tumor. However, few imaging patterns are specific for a particular pathological process and useful conclusions can be made from the morphological appearance of the lesion, its location and enhancement pattern. The aim of this article was to review and illustrate the CT and MRI findings of a wide spectrum of tumors of the lateral ventricle. We reviewed choroid plexus tumors, meningioma, subependymal giant cell astrocytoma, central neurocytoma, and less frequent lesion such as lymphoma and metastases.

Early ADC changes in motor structures predict outcome of acute stroke better than lesion volume.

OBJECTIVES: The lesion volume assessed from diffusion-weighted imaging (DWI) within the first six hours to first week following stroke onset has been proposed as a predictor of functional outcome in clinical studies. However, the prediction accuracy decreases when the DWI lesion volume is measured during the earliest stages of patient evaluation. In this study, our hypothesis was that the combination of lesion location (motor-related regions) and diffusivity measures (such as Apparent Diffusion Coefficient [ADC]) at the acute stage of stroke predict clinical outcome. PATIENTS AND METHODS: Seventy-nine consecutive acute carotid territory stroke patients (median age: 62 years) were included in the study and outcome at three months was assessed using the modified Rankin scale (good outcome: mRS 0-2; poor outcome: mRS 3-5). DWI was acquired within the first six hours of stroke onset (H2) and the following day (D1). Apparent Diffusion Coefficient (ADC) values were measured in the corticospinal tract (CST), the primary motor cortex (M1), the supplementary motor area (SMA), the putamen in the affected hemisphere, and in the contralateral cerebellum to predict stroke outcome. RESULTS: Prediction of poor vs. good outcome at the individual level at H2 (D1, respectively) was achieved with 74% accuracy, 95%CI: 53-89% (75%, 95% CI: 61-89%, respectively) when patients were classified from ADC values measured in the putamen and CST. Prediction accuracy from DWI volumes reached only 62% (95%CI: 42-79%) at H2 and 69% (95%CI: 50-85%) at D1. CONCLUSION: We therefore show that measures of ADC at the acute stage in deeper motor structures (putamen and CST) are better predictors of stroke outcome than DWI lesion volume.

Usefulness of MR imaging for the assessment of nonophthalmic paraclinoid aneurysms.

BACKGROUND AND PURPOSE: The neuroradiologic location of asymptomatic paraclinoid aneurysms is decisive for patient management. In a preliminary study, we designed a paraclinoid MR protocol (PMP) including high-resolution T2-weighted images in 2 orthogonal planes to define the inferior limit of the distal dural ring plane that represents the borderline between the intradural and extradural internal carotid artery. In this clinical study, we compared this protocol with digital subtraction angiography (DSA) for the location of paraclinoid aneurysms. MATERIALS AND METHODS: During a 3-year period, we performed PMP and conventional angiograms in 14 consecutive patients with 17 asymptomatic paraclinoid aneurysms. Ophthalmic (superior) aneurysms were excluded. Two independent observers reviewed MR imaging data, and a third experienced neuroradiologist analyzed the conventional angiograms. MR imaging and conventional angiograms were independently analyzed, and interpretations obtained with each technique were compared. RESULTS: PMP allowed correct visualization of the aneurysms in all patients. No significant differences (P >.05) were found between the DSA and PMP for the measurement of the aneurysmal neck or sac. Interobserver agreement was good. MR imaging was discordant with conventional angiography regarding the position around the cavernous sinus of the aneurysmal neck and sac in 5 cases. PMP images were helpful for treatment decisions in 4 cases. CONCLUSION: PMP is an interesting tool that might be used in association with conventional angiography for the assessment of paraclinoid aneurysms.

Structural abnormalities in the cerebellum and sensorimotor circuit in writer's cramp.

BACKGROUND: Structural abnormalities were detected in bilateral primary sensorimotor areas in writer's cramp. Evidence in other primary dystonia, including blepharospasm and cervical dystonia, suggest that structural abnormalities may be observed in other brain areas such as the cerebellum in writer's cramp. OBJECTIVE: To test the hypothesis that structural abnormalities are present along the sensorimotor and cerebellar circuits in patients with writer's cramp. METHODS: Using voxel-based morphometry, the authors compared the brain structure of 30 right-handed patients with writer's cramp with that of 30 healthy control subjects matched for gender, age, and handedness. RESULTS: Gray matter decrease was found in the hand area of the left primary sensorimotor cortex, bilateral thalamus, and cerebellum (height threshold p < 0.01, cluster significant at p < 0.05 corrected for multiple comparisons). CONCLUSIONS: These results demonstrate in writer's cramp the presence of structural abnormalities in brain structures interconnected within the sensorimotor network including the cerebellum and the cortical representation of the affected hand. These abnormalities may be related to the pathophysiology of writer's cramp, questioning the role of the cerebellum, or to maladaptive plasticity in a task-related dystonia.

[Functional magnetic resonance imaging: physiopathology, techniques and applications]. / IRM fonctionnelle cérébrale: bases physiologiques, techniques et applications cliniques.

Brain functional MRI (fMRI) provides an indirect mapping of cerebral activity, based on the detection of local changes in blood flow and oxygenation levels that are associated with neuronal activity (BOLD contrast). fMRI allows noninvasive studies of normal and pathological aspects of the brain's functional organization. It is based on the comparison of two or more cognitive states. Echoplanar imaging is the technique of choice, providing the quickest study of the entire brain. Activation maps are calculated from a statistical analysis of the local signal changes. fMRI has become one of the most widely used functional imaging techniques in neuroscience. In clinical practice, fMRI can identify eloquent areas involved in motor and language functions in surgical patients and can evaluate the risk of postoperative neurological deficit.