FIBRASCAN: a novel method for 3D white matter tract reconstruction in MR space from cadaveric dissection.

INTRODUCTION: Diffusion tractography relies on complex mathematical models that provide anatomical information indirectly, and it needs to be validated. In humans, up to now, tractography has mainly been validated by qualitative comparison with data obtained from dissection. No quantitative comparison was possible because Magnetic Resonance Imaging (MRI) and dissection data are obtained in different reference spaces, and because fiber tracts are progressively destroyed by dissection. Here, we propose a novel method and software (FIBRASCAN) that allow accurate reconstruction of fiber tracts from dissection in MRI reference space. METHOD: Five human hemispheres, obtained from four formalin-fixed brains were prepared for Klingler's dissection, placed on a holder with fiducial markers, MR scanned, and then dissected to expose the main association tracts. During dissection, we performed iterative acquisitions of the surface and texture of the specimens using a laser scanner and two digital cameras. Each texture was projected onto the corresponding surface and the resulting set of textured surfaces was coregistered thanks to the fiducial holders. The identified association tracts were then interactively segmented on each textured surface and reconstructed from the pile of surface segments. Finally, the reconstructed tracts were coregistered onto ex vivo MRI space thanks to the fiducials. Each critical step of the process was assessed to measure the precision of the method. RESULTS: We reconstructed six fiber tracts (long, anterior and posterior segments of the superior longitudinal fasciculus; Inferior fronto-occipital, Inferior longitudinal and uncinate fasciculi) from cadaveric dissection and ported them into ex vivo MRI reference space. The overall accuracy of the method was of the order of 1mm: surface-to-surface registration=0.138mm (standard deviation (SD)=0.058mm), deformation of the specimen during dissection=0.356mm (SD=0.231mm), and coregistration surface-MRI=0.6mm (SD=0.274mm). The spatial resolution of the method (distance between two consecutive surface acquisitions) was 0.345mm (SD=0.115mm). CONCLUSION: This paper presents the robustness of a novel method, FIBRASCAN, for accurate reconstruction of fiber tracts from dissection in the ex vivo MR reference space. This is a major step toward quantitative comparison of MR tractography with dissection results.

Combined 1H-NMR and 1H-13C HSQC-NMR to improve urinary screening in autism spectrum disorders.

Autism spectrum disorders (ASD) are neurodevelopmental diseases with complex genetic and environmental etiological factors. Although genetic causes play a significant part in the etiology of ASD, metabolic disturbances may also play a causal role or modulate the clinical features of ASD. The number of ASD studies involving metabolomics is increasing, and sometime with conflicting findings. We assessed the metabolomics profiling of urine samples to determine a comprehensive biochemical signature of ASD. Furthermore, to date no study has combined metabolic profiles obtained from different analytical techniques to distinguish patient with ASD from healthy individuals. We obtained (1)H-NMR spectra and 2D (1)H-(13)C HSQC NMR spectra from urine samples of patients with ASD or healthy controls. We analyzed these spectra by multivariate statistical data analysis. The OPLS-DA model obtained from (1)H NMR spectra showed a good discrimination between ASD samples and non-ASD samples (R(2)Y(cum) = 0.70 and Q(2) = 0.51). Combining the (1)H NMR spectra and the 2D (1)H-(13)C HSQC NMR spectra increased the overall quality and predictive value of the OPLS-DA model (R(2)Y(cum) = 0.84 and Q(2) = 0.71), leading to a better sensitivity and specificity. Urinary excretion of succinate, glutamate and 3-methyl-histidine differed significantly between ASD and non-ASD samples. Urinary screening of children with neurodevelopmental disorders by combining NMR spectroscopies (1D and 2D) in multivariate analysis is a better sensitive and a straightforward method that could help the diagnosis ASD.

Maternal deprivation and milk replacement affect the integrity of gray and white matter in the developing lamb brain.

The psychoendocrine evaluation of lamb development has demonstrated that maternal deprivation and milk replacement alters health, behavior, and endocrine profiles. While lambs are able to discriminate familiar and non-familiar conspecifics (mother or lamb), only lambs reared with their mother develop such clear social discrimination or preference. Lambs reared without mother display no preference for a specific lamb from its own group. Differences in exploratory and emotional behaviors between mother-reared and mother-deprived lambs have also been reported. As these behavioural abilities are supported by the brain, we hypothesize that rearing with maternal deprivation and milk replacement leads to altered brain development and maturation. To test this hypothesis, we examined brain morphometric and microstructural variables extracted from in vivo T1-weighted and diffusion-weighted magnetic resonance images acquired longitudinally (1 week, 1.5 months, and 4.5 months of age) in mother-reared and mother-deprived lambs. From the morphometric variables the caudate nuclei volume was found to be smaller for mother-deprived than for mother-reared lambs. T1-weighted signal intensity and radial diffusivity were higher for mother-deprived than for mother-reared lambs in both the white and gray matters. The fractional anisotropy of the white matter was lower for mother-deprived than for mother-reared lambs. Based on these morphometric and microstructural characteristics we conclude that maternal deprivation delays and affects lamb brain growth and maturation.

Quantitative estimation of thrombus-erythrocytes using MRI. A phantom study with clot analogs and analysis by statistic regression models.

BACKGROUND: Thrombus composition has the potential to affect acute ischemic stroke (AIS) treatment. OBJECTIVE: To evaluate in an in vitro test the correlation of clot composition, especially erythrocytes (red blood cells (RBCs)), with the variation of signal intensity ratio (SIR) obtained with MRI sequences used for AIS, and qualification of the susceptibility vessel sign effect using clot analogs. MATERIALS AND METHODS: Nine ovine clots were fixed in a gelatin-manganese solution and studied by MRI (T2GE, T2-weighted gradient echo; SWI, susceptibility-weighted imaging; FLAIR, fluid attenuated inversion recovery). RBC concentration was estimated using regression models (SLR, single linear regression; MLR, multiple linear regression; RF, random Forest; and ANN, artificial neural networking), which combined the SIR-histology relationship of three MRI sequences. RESULTS: Negative correlation was found between SIR and RBC concentration. T2GE SWI could not statistically distinguish clots with RBC content >54% and <23%. SLR was applied only to FLAIR images since T2GE and SWI demonstrated signal saturation. All four regression models showed a correlation between MRI and histology: SLR=0.981; MLR=0.986; RF=0.994, and ANN=0.971. One unknown clot was studied and agreement between SIR and histological analyses was found in all models. CONCLUSIONS: We presented a method to quantify RBC concentration in clot analogs, combining SWI, T2GE, and FLAIR. This in vitro study has some limitations, so clot collection after thrombectomy with simultaneous imaging analysis is necessary to validate this model.

Sex-specific effects of COMT Val158Met polymorphism on corpus callosum structure: A whole-brain diffusion-weighted imaging study.

BACKGROUND: Genetic polymorphisms play a significant role in determining brain morphology, including white matter structure and may thus influence the development of brain functions. The main objective of this study was to examine the effect of Val158Met (rs4680) polymorphism of Catechol-O-Methyltransferase (COMT) gene on white matter connectivity in healthy adults. METHODS: We used a whole-brain diffusion-weighted imaging method with Tract-Based Spatial Statistics (TBSS) analysis to examine white matter structural integrity in intrinsic brain networks on a sample of healthy subjects (N = 82). RESULTS: Results revealed a sex-specific effect of COMT on corpus callosum (CC): in males only, Val homozygotes had significantly higher fractional anisotropy (FA) compared to Met-carriers. Volume-of-interest analysis showed a genotype by sex interaction on FA in genu and rostral midbody of CC, whereby Val males demonstrated higher FA than Met females. CONCLUSIONS: These results demonstrate the key effect of genes by sex interaction, rather than their individual contribution, on the corpus callosum anatomy.

Natural course and prognosis of anaplastic gangliogliomas: a multicenter retrospective study of 43 cases from the French Brain Tumor Database.

Background: Anaplastic gangliogliomas (GGGs) are rare tumors whose natural history is poorly documented. We aimed to define their clinical and imaging features and to identify prognostic factors. Methods: Consecutive cases of anaplastic GGGs in adults prospectively entered into the French Brain Tumor Database between March 2004 and April 2014 were screened. After diagnosis was confirmed by pathological review, clinical, imaging, therapeutic, and outcome data were collected retrospectively. Results: Forty-three patients with anaplastic GGG (median age, 49.4 y) from 18 centers were included. Presenting symptoms were neurological deficit (37.2%), epileptic seizure (37.2%), or increased intracranial pressure (25.6%). Typical imaging findings were unifocal location (94.7%), contrast enhancement (88.1%), central necrosis (43.2%), and mass effect (47.6%). Therapeutic strategy included surgical resection (95.3%), adjuvant radiochemotherapy (48.8%), or radiotherapy alone (27.9%). Median progression-free survival (PFS) and overall survival (OS) were 8.0 and 24.7 months, respectively. Three- and 5-year tumor recurrence rates were 69% and 100%, respectively. The 5-year survival rate was 24.9%. Considering unadjusted significant prognostic factors, tumor midline crossing and frontal location were associated with shorter OS. Temporal and parietal locations were associated with longer and shorter PFS, respectively. None of these factors remained statistically significant in multivariate analysis. Conclusions: We report a large series providing clinical, imaging, therapeutic, and prognostic features of adult patients treated for an intracerebral anaplastic GGG. Our results show that pathological diagnosis is difficult, that survivals are only slightly better than for glioblastomas, and that complete surgical resection followed with adjuvant chemoradiotherapy offers longer survival.