Vanishing white matter disease: imaging, clinical and molecular correlation in Brazilian families.

PURPOSE: To characterize Vanishing White Matter Disease (VWM) cases from a Brazilian University Tertiary hospital, focusing on brain magnetic resonance image (MRI) aspects, clinical and molecular data. METHODS: Medical records and brain MRI of 13 genetically confirmed VWM patients were reviewed. Epidemiological data such as age at symptom onset, gender and main symptoms were analyzed, along with genetic mutations and MRI characteristics, such as the distribution of white matter lesions and atrophy. RESULTS: The majority of patients were female, with the age of symptom onset ranging from 1 year and 6 months to 40 years. All mutations were identified in the EIF2B5 gene, the most prevalent being c.338G > A (p.Arg113His), and a novel mutation related to the disease was discovered, c.1051G > A (p.Gly351Ser). Trauma or infection were significant triggers. The most frequent symptoms were ataxia and limb spasticity. All MRI scans displayed deep white matter involvement, cystic degeneration, with U-fibers relatively spared and a predilection for the frontoparietal region. Lesions in the corpus callosum and posterior fossa were present in all patients. Follow-up exams revealed the evolution of white matter lesions and cerebral atrophy, which correlated with clinical deterioration. CONCLUSIONS: VWM affects various age groups, with a significant clinical and genetic variability. A novel mutation associated with the disease is highlighted. MRI reveals a typical pattern of white matter involvement, characterized by diffuse lesions in the periventricular and deep regions, with subsequent extension to the subcortical areas, accompanied by cystic degeneration, and plays a crucial role in diagnosis and follow-up.

Clinical and Surgical Approach for Cerebral Cortical Dysplasia.

The present article describes pathophysiological and clinical aspects of congenital malformations of the cerebral tissue (cortex and white matter) that cause epilepsy and very frequently require surgical treatment. A particular emphasis is given to focal cortical dysplasias, the most common pathology among these epilepsy-related malformations. Specific radiological and surgical features are also highlighted, so a thorough overview of cortical dysplasias is provided.

Contrast agent-free state-of-the-art magnetic resonance imaging on cerebral small vessel disease - Part 2: Diffusion tensor imaging and functional magnetic resonance imaging.

Cerebral small vessel disease (cSVD) has been widely studied using conventional magnetic resonance imaging (MRI) methods, although the association between MRI findings and clinical features of cSVD is not always concordant. We assessed the additional contribution of contrast agent-free, state-of-the-art MRI techniques, particularly diffusion tensor imaging (DTI) and functional magnetic resonance imaging (fMRI), to understand brain damage and structural and functional connectivity impairment related to cSVD. We performed a review following the PICOS worksheet and Search Strategy, including 152 original papers in English, published from 2000 to 2022. For each MRI method, we extracted information about their contributions regarding the origins, pathology, markers, and clinical outcomes in cSVD. In general, DTI studies have shown that changes in mean, radial, and axial diffusivity measures are related to the presence of cSVD. In addition to the classical deficit in executive functions and processing speed, fMRI studies indicate connectivity dysfunctions in other domains, such as sensorimotor, memory, and attention. Neuroimaging metrics have been correlated with the diagnosis, prognosis, and rehabilitation of patients with cSVD. In short, the application of contrast agent-free, state-of-the-art MRI techniques has provided a complete picture of cSVD markers and tools to explore questions that have not yet been clarified about this clinical condition. Longitudinal studies are desirable to look for causal relationships between image biomarkers and clinical outcomes.

Contrast-agent-free state-of-the-art MRI on cerebral small vessel disease-part 1. ASL, IVIM, and CVR.

Cerebral small vessel disease (cSVD), a common cause of stroke and dementia, is traditionally considered the small vessel equivalent of large artery occlusion or rupture that leads to cortical and subcortical brain damage. Microvessel endothelial dysfunction can also contribute to it. Brain imaging, including MRI, is useful to show the presence of lesions of several types, although the association between conventional MRI measures and clinical features of cSVD is not always concordant. We assessed the additional contribution of contrast-agent-free, state-of-the-art MRI techniques such as arterial spin labeling (ASL), diffusion tensor imaging, functional MRI, and intravoxel incoherent motion (IVIM) applied to cSVD in the existing literature. We performed a review following the PICO Worksheet and Search Strategy, including original papers in English, published between 2000 and 2022. For each MRI method, we extracted information about their contributions, in addition to those established with traditional MRI methods and related information about the origins, pathology, markers, and clinical outcomes in cSVD. This paper presents the first part of the review, which includes 37 studies focusing on ASL, IVIM, and cerebrovascular reactivity (CVR) measures. In general, they have shown that, in addition to white matter hyperintensities, alterations in other neuroimaging parameters such as blood flow and CVR also indicate the presence of cSVD. Such quantitative parameters were also related to cSVD risk factors. Therefore, they are promising, noninvasive tools to explore questions that have not yet been clarified about this clinical condition. However, protocol standardization is essential to increase their clinical use.

Age-related assessment of diffusion parameters in specific brain tracts correlated with cortical thinning.

The aging process is associated with many brain structural alterations. These changes are not associated with neuronal loss but can be due to cortical structural changes that may be related to white matter (WM) structural alterations. In this study, we evaluated age-related changes in WM and gray matter (GM) parameters and how they correlate for specific brain tracts in a cohort of 158 healthy individuals, aged between 18 and 83 years old. In the tract-cortical analysis, cortical regions connected by tracts demonstrated similar thinning patterns for the majority of tracts. Additionally, a significant relationship was found between mean cortical thinning rate with fractional anisotropy (FA) and mean diffusivity (MD) alteration rates. For all tracts, age was the main effect controlling diffusion parameter alterations. We found no direct correlations between cortical thickness and FA or MD, except for in the fornix, for which the subcallosal gyrus thickness was significantly correlated to FA and MD (p < 0.05 FDR corrected). Our findings lead to the conclusion that alterations in the WM diffusion parameters are explained by the aging process, also associated with cortical thickness changes. Also, the alteration rates of the structural parameters are correlated to the different brain tracts in the aging process.

Contrast optimization in arterial spin labeling with multiple post-labeling delays for cerebrovascular assessment.

OBJECTIVE: Improving the readout for arterial spin labeling with multiple post-labeling delays (multi-PLD ASL) through a flip angle (FA) sweep towards increasing contrast-to-noise ratio for long PLD images. METHODS: Images were acquired from 20 healthy subjects and 14 patients with severe, asymptomatic carotid artery stenosis (ACAS) in a 3T MRI scanner. Multi-PLD ASL images with conventional and proposed (FA sweep) readouts were acquired. For patients, magnetic resonance angiography was used to validate the multi-PLD ASL results. Perfusion values were calculated for brain regions irrigated by the main cerebral arteries and compared by analysis of variance. RESULTS: For healthy subjects, better contrast was obtained for long PLDs when using the proposed multi-PLD method compared to the conventional. For both methods, no hemispheric difference of perfusion was observed. For patients, the proposed method facilitated the observation of delayed tissue perfusion, which was not visible for long PLD using the conventional multi-PLD ASL. CONCLUSION: We successfully assessed brain perfusion of patients with asymptomatic CAS using multi-PLD ASL with FA sweep. We were able to show subtle individual differences. Moreover, prolonged arterial transit time in patients was observed, although they were considered asymptomatic, suggesting that it may not be an adequate term to characterize them.

Evaluating H3F3A K27M and G34R/V somatic mutations in a cohort of pediatric brain tumors of different and rare histologies.

PURPOSE: Somatic mutations on H3 histone are currently considered a genetic hallmark for midline pediatric high-grade gliomas (HGGs). Yet, different tumor histologies have been occasionally described to carry these mutations. Since histone modifications can lead to major epigenetic changes with direct impact on prognosis and treatment, we thought to investigate the occurrence of H3F3A K27M and G34R/V mutations in a cohort of pediatric tumors which included HGGs, low-grade gliomas, ependymomas, medulloblastomas, and a series of rare brain tumor lesions of different histologies. METHODS: A total of 82 fresh-frozen pediatric brain tumor samples were evaluated. PCR or RT-PCR followed by Sanger sequencing for the exon 2 of H3F3A (containing both K27 and G34 hotspots) were obtained and aligned to human genome. Loss of trimethylation mark (H3K27me3) in H3F3A/K27M-mutant samples was confirmed by immunohistochemistry. RESULTS: We found H3F3A/K27M mutation in 2 out of 9 cases of HGGs; no H3F3A/K27M mutations were detected in low-grade gliomas (27), ependymomas (n = 10), medulloblastomas (n = 21), or a series of rare pediatric brain tumors which included meningiomas, dysembryoplastic neuroepithelial tumors (DNETs), central nervous system (CNS) germ-cell tumors, choroid plexus tumors, cortical hamartoma, subcortical tubers, and schwannomas (n = 15). H3F3A/G34R/V mutation was not observed in any of the samples. CONCLUSIONS: Our investigation reinforces the low frequency of H3F3A somatic mutations outside the HGG setting. Interestingly, an atypical focal brainstem glioma carrying H3F3A K27M mutation that showed protracted clinical course with late-onset tumor progression was identified.

Impact of epilepsy surgery on quality of life and burden of caregivers in children and adolescents.

OBJECTIVE: The objective of this study was to analyze the impact of pediatric epilepsy surgery on the quality of life (QOL), determining whether patients improve, worsen, or maintain their preoperative patterns, as it relates to the burden of caregivers, as well as evaluating potential related factors, from both the children and caregivers perspectives. MATERIAL AND METHODS: This is a retrospective study of children and adolescents who underwent epilepsy surgery and were evaluated through clinical data, videoelectroencephalogram (V-EEG), neuroimaging findings, neuropsychological testing, and aspects of QOL. These assessments were performed prior to surgery and after six months and two years of follow-up. Quality of life was assessed with epilepsy-specialized questionnaires, namely Questionnaire health-related quality of life for children with epilepsy (QVCE-50), Autoquestionnaire Qualité de Vie Enfant Image Scale (AUQUEI), Quality of life in epilepsy inventory for adolescents (QOLEI-AD-48); and burden of caregivers with Burden Interview - ZARIT scale. Postoperative changes in QVCE-50 were quantified using measures of the analysis of variance (ANOVA MR) for comparison of the difference between the three times of the scale and domains. RESULTS: Fifty patients were enrolled. Of these, 27 (54%) were male, with a mean age at surgery of 8.2 years (range: 1-18 years). Thirty-five patients (70%) were Engel I and one was Engel II (2%) at six months of follow-up, whereas 28 (56%) were Engel I and 32 (64%) were Engel I or II at two years of follow-up. Preoperatively, 21 (42%) presented with moderate or severe intellectual disability. Postoperative cognitive evaluations at the two-year follow-up showed 18 (36%) maintained similar deficits. The QVCE-50 showed postoperative improvement in the two-year follow-up period, but not at six months after surgery. Postoperative improvements were associated mainly with better seizure outcome. Autoperception evaluations were limited because of the clinical and cognitive severity of patients. The burden of caregivers was quoted as mild to moderate and remained unchanged postoperatively. CONCLUSIONS: Children and adolescents with surgically treated epilepsy reach a good seizure outcome, stabilize in intellectual and adaptive functions, and have an increase in QOL, from the caregiver's perspective. Nevertheless, their burden remains unchanged. Seizure outcome is the main factor for improvement in the QOL. The upgrading of structured questionnaires and QOL instruments specific to pediatric epilepsy can be helpful to assess patient- and caregiver-reported surgical outcomes, allowing for better planning of therapeutic approaches.

Urbanicity and risk of first-episode psychosis: incidence study in Brazil.

We estimated the incidence of first-episode psychosis over a 3-year period in a Brazilian catchment area comprising the region's main city, Ribeirão Preto (1 425 306 persons-years at risk), and 25 other municipalities with a total of 1 646 556 persons-years at risk. The incidence rates were estimated and adjusted by gender and age, using the direct standardisation method to the world population as reference. The incidence of psychosis was higher in the younger groups, men, and among Black and minority ethnic Brazilians. Psychosis incidence was lower in Ribeirão Preto (16.69/100 000 person-years at risk; 95% CI 15.68-17.70) compared with the average incidence in the remaining municipalities (21.25/100 000 person-years at risk; 95% CI 20.20-22.31), which have lower population density, suggesting a distinct role for urbanicity in the incidence of first-episode psychosis in low- and middle-income countries.

Monitoring optic chiasmatic-hypothalamic glioma volumetric changes by MRI in children under clinical surveillance or chemotherapy.

PURPOSE: Optic pathway gliomas represent 5% of pediatric brain tumors and are typically low-grade lesions. Because of their unpredictable clinical course, adequate treatment approaches have been controversial, involving surveillance, surgery, chemotherapy, and radiotherapy. In this study, we use volumetric imaging to compare evolution of optic chiasmatic-hypothalamic gliomas (OCHG) treated with and without chemotherapy, analyzing tumor volume variation during the overall period. METHODS: A total of 45 brain MRI were retrospectively analyzed for 14 patients with OCHG. Volumetric assessment of the lesions was performed by a neuroradiologist, using software DISPLAY. OCHG patients were allocated into two groups: group 1 (n = 8) who underwent chemotherapy and group 2 (n = 6) who did not receive chemotherapy. Outcome analysis was performed comparing tumor volume evolution of these two groups. RESULTS: The results showed a reduction of 4.4% of the volume of the lesions for group 1 after the end of chemotherapy, with an increase of 5.3% in volume in the late follow-up examination. For group 2, we found a slight reduction (5%) of the overall volume of the lesions, both with no statistical significance (p > 0.05). CONCLUSIONS: From the limited series analyzed in this study, no significant differences were observed in relation to the volume change of lesions treated or not treated with chemotherapy. Larger prospective clinical trials are needed to better evaluate the effect of chemotherapy and radiological response of OCHG.

Neurofunctional changes after a single mirror therapy intervention in chronic ischemic stroke.

BACKGROUND: Mirror therapy (MT) is becoming an alternative rehabilitation strategy for various conditions, including stroke. Although recent studies suggest the positive benefit of MT in chronic stroke motor recovery, little is known about its neural mechanisms. PURPOSE: To identify functional brain changes induced by a single MT intervention in ischemic stroke survivors, assessed by both transcranial magnetic stimulation (TMS) and functional magnetic resonance imaging (fMRI). MATERIALS AND METHODS: TMS and fMRI were used to investigate 15 stroke survivors immediately before and after a single 30-min MT session. RESULTS: We found statistically significant increase in post-MT motor evoked potential (MEP) amplitude (increased excitability) from the affected primary motor cortex (M1), when compared to pre-MT MEP. Post-MT fMRI maps were associated with a more organized and constrained pattern, with a more focal M1 activity within the affected hemisphere after MT, limited to the cortical area of hand representation. Furthermore, we find a change in the balance of M1 activity toward the affected hemisphere. In addition, significant correlation was found between decreased fMRI ß-values and increased MEP amplitude post-MT, in the affected hemisphere. CONCLUSION: Our study suggests that a single MT intervention in stroke survivors is related to increased MEP of the affected limb, and a more constrained activity of the affected M1, as if activity had become more constrained and limited to the affected hemisphere.

Understanding the association of neurocysticercosis and mesial temporal lobe epilepsy and its impact on the surgical treatment of patients with drug-resistant epilepsy.

Mesial temporal lobe epilepsy associated with hippocampal sclerosis (MTLE-HS) is one of the most common types of focal epilepsies. This is an epileptic syndrome commonly associated with treatment-resistant seizures, being also the most prevalent form of drug-resistant epilepsy which is treated surgically in most epilepsy surgery centers. Neurocysticercosis (NCC) is one of the most common parasitic infections of the central nervous system, and one of the most common etiological agents of focal epilepsy, affecting millions of patients worldwide. Recently, researchers reported a curious association between MTLE-HS with NCC, but this association remains poorly understood. Some argue that calcified NCC lesions in MTLE-HS patients is only a coincidental finding, since both disorders are prevalent worldwide. However, others suppose there might exist a pathogenic relationship between both disorders and some even suspect that NCC, by acting as an initial precipitating injury (IPI), might cause hippocampal damage and, eventually, MTLE-HS. In this review, we discuss the various reports that examine this association, and suggest possible explanations for why calcified NCC lesions are also observed in patients with MTLE-HS. We also propose mechanisms by which NCC could lead to MTLE-HS. Finally, we discuss the implications of NCC for the treatment of pharmacologically-resistant focal epilepsies in patients with calcified NCC or in patients with MTLE-HS and calcified NCC lesions. We believe that investigations in the relationship between NCC and MTLE-HS might offer further insights into how NCC may trigger epilepsy, and into how MTLE-HS originates. Moreover, observations in patients with drug-resistant epilepsy with both NCC and hippocampal sclerosis may not only aid in the understanding and treatment of patients with MTLE-HS, but also of patients with other forms of dual pathologies aside from NCC. This article is part of a Special Issue titled Neurocysticercosis and Epilepsy.

Environmental enrichment reduces brain damage in hydrocephalic immature rats.

PURPOSE: We investigate the effects of environmental enrichment (EE) on morphological alterations in different brain structures of pup rats submitted to hydrocephalus condition. METHODS: Hydrocephalus was induced in 7-day-old pup rats by injection of 20% kaolin into the cisterna magna. Ventricular dilatation and magnetization transfer to analyze myelin were assessed by magnetic resonance. Hydrocephalic and control rats exposed to EE (n = 10 per group) were housed in cages with a tunnel, ramp, and colored plastic balls that would emit sound when touched. The walls of the housing were decorated with colored adhesive tape. Moreover, tactile and auditory stimulation was performed daily throughout the experiment. Hydrocephalic and control rats not exposed to EE (n = 10 per group) were allocated singly in standard cages. All animals were weighed daily and exposed to open-field conditions every 2 days until the end of the experiment when they were sacrificed and the brains removed for histology and immunohistochemistry. Solochrome cyanine staining was performed to assess the thickness of the corpus callosum. The glial fibrillary acidic protein method was used to evaluate reactive astrocytes, and the Ki67 method to assess cellular proliferation in the subventricular zone. RESULTS: The hydrocephalic animals exposed to EE showed better performance in Open Field tests (p < 0.05), while presenting lower weight gain. In addition, these animals showed better myelination as revealed by magnetization transfer (p < 0.05). Finally, the EE group showed a reduction in reactive astrocytes by means of glial fibrillary acidic protein immunostaining and preservation of the proliferation potential of progenitor cells. CONCLUSION: The results suggest that EE can protect the developing brain against damaging effects caused by hydrocephalus.

Pre- and postshunting magnetization transfer ratios are in accordance with neurological and behavioral changes in hydrocephalic immature rats.

Hydrocephalus is a common neurological condition in children characterized by an imbalance between the production and absorption of cerebrospinal fluid (CSF), causing abnormal fluid accumulation in the brain cavities. Shunt systems have been used to drain excess CSF and to prevent progressive ventricular enlargement. However, despite improvements in these systems, neurological and structural changes cannot always be reversed. Our aim was to evaluate the magnetization transfer ratio as a biomarker for the effectiveness of a CSF shunt system to treat neurological and behavioral disorders observed in experimental hydrocephalus. Seven-day-old Wistar rats were used in this study. The pups were subjected to hydrocephalus induction via 20% kaolin intracisternal injection. After confirmation of ventriculomegaly by magnetic resonance imaging (MRI), a group of animals underwent placement of a ventriculosubcutaneous shunt (VSS). The reduction in ventricular size in hydrocephalic rats operated with functional VSS was observed as a decrease in ventricular ratio values and preservation of the corpus callosum thickness. Magnetization transfer values were significantly increased and matched to the recovery process of axonal myelination observed based on more-intense blue staining by solochrome cyanin. The histopathological analysis revealed a reduction in reactive astrocytes by means of GFAP immunostaining. The hydrocephalic rats operated with functional VSS also showed significant progress in motor and exploratory activities, similar to the control animals, at the end of the experiment. In conclusion, the VSS system employed 7 days after hydrocephalus induction was able to prevent structural damage and restore the axonal myelination process in periventricular structures by stabilizing and reducing the ventricular enlargement, and the results are in accordance with the magnetization transfer ratio in MRI.

Do young patients have different clinical presentation of colorectal cancer causing delay in diagnosis?

PURPOSE: The incidence of colorectal cancer is increasing among young patients. In these patients, colorectal cancer is believed to have a poorer prognosis because it is more aggressive and diagnosed at later stages; however, the behavior of these tumors in young patients remains to be elucidated. We investigated the impact of time interval between onset of symptoms and diagnosis (TISD) at the pathologic stage of colorectal cancer in young patients. METHODS: The medical records of 215 patients with colorectal adenocarcinoma were reviewed. Patients were divided into two groups according to age. The young group (age < 50 years) consisted of 66 patients, and the older group (age ≥ 50 years) of 149 patients. Clinical variables, TISD, pathologic stage, operative mortality, and oncologic outcomes were compared between groups. RESULTS: The older group had less abdominal pain (74.0 vs. 56.0 %, p = 0.0129). In multivariate analysis, the following variables were independently associated with tumor pathologic stage: personal history of inflammatory bowel disease (p < 0.0001), family history of familial adenomatous polyposis (p = 0.00100), and smoking (p = 0.0070). Both groups had similar rates regarding pathologic stage (I, 15 vs. 22 %; II, 22 vs. 24 %; III, 27 vs. 16 %; IV, 37 vs. 38 %, p = 0.3380). There was no difference in overall survival [45 (69 %) vs. 84 (61 %), p = 0.2482] and cancer-free survival [36 (63 %) vs. 83 (62 %), p = 0.9218] between groups. CONCLUSIONS: Young patients with colorectal cancer had clinical and pathological presentation similar to that of older patients.

Surgery for focal cortical dysplasia in children using intraoperative mapping.

OBJECTIVE: Children with malformation of cortical development represent a significant proportion of pediatric epilepsy surgery candidates. Here, we describe a single-center experience with pediatric patients who underwent surgery for intractable epilepsy due to focal cortical dysplasia (FCD). METHODS: Clinical data of 78 patients under 18 years of age with diagnosis of intractable epilepsy due to FCD who underwent surgery from January 1996 to January 2012 were reviewed comparing data of patients submitted to electrocorticography (ECoG) with those without ECoG. RESULTS: Patients' mean age at surgery was 8.52 ± 4.99 years; mean age at epilepsy onset was 2.55 ± 3.01 years. Almost 80 % of the patients underwent ECoG register that was essential for delimitation of surgical resection in 66 out of 78 patients. ECoG was performed in all patients with extratemporal lesions, and the most common FCD found was type II. Seizure outcome was similar in groups with or without ECoG. CONCLUSIONS: Tailored resection of FCD lesions for intractable epilepsy can be safely performed in children with a good seizure outcome and low complication rate. Epilepsy surgery should be considered for all patients with FCD and refractory epilepsy.

Symmetrical placement of bilateral percutaneous bone-anchored hearing systems via guide-marker.

Objectives: To investigate the use of a novel technique to estimate the symmetrical placement of percutaneous bone-anchored hearing systems (BAHS) with a guide-marker in patients undergoing bilateral surgery with this device. Study Design: Prospective cohort study. Methods: A guide-marker and anatomical landmarks were used to estimate the implant placement and transferred to the contralateral ear in 12 subjects eligible for bilateral BAHS surgery. To investigate the bilateral symmetry, preoperative tri-dimensional (3D) computed tomography (CT) image reconstruction was used to compare the distances between the mandibular condyle and implant placement estimation (mandible-implant distance) in both the right and left ears of the subjects. Results: The guide-marker could be used to estimate the bilateral implant placement in all subjects included in this study, simply and easily, including one subject with craniofacial malformation. The mean mandible-implant distances were 5.37 and 5.38 cm, in the right and left ears of the subjects, respectively, and no differences were observed between them, thereby indicating optimal bilateral symmetry. Conclusion: The use of the guide-marker proved to be an effective tool to provide symmetrical placement of bilateral BAHS. We propose a novel method employing a simple guide-marker and tracing based on symmetrical anatomical landmarks to achieve precise placement and optimal symmetry and which may be easily adopted in the surgical routine of BAHS. Level of Evidence: 3.

Assessment of U-Net in the segmentation of short tracts: Transferring to clinical MRI routine.

Accurately studying structural connectivity requires precise tract segmentation strategies. The U-Net network has been widely recognized for its exceptional capacity in image segmentation tasks and provides remarkable results in large tract segmentation when high-quality diffusion-weighted imaging (DWI) data are used. However, short tracts, which are associated with various neurological diseases, pose specific challenges, particularly when high-quality DWI data acquisition within clinical settings is concerned. Here, we aimed to evaluate the U-Net network ability to segment short tracts by using DWI data acquired in different experimental conditions. To this end, we conducted three types of training experiments involving 350 healthy subjects and 11 white matter tracts, including the anterior, posterior, and hippocampal commissure, fornix, and uncinated fasciculus. In the first experiment, the model was exclusively trained with high-quality data of the Human Connectome Project (HCP) dataset. The second experiment focused on images of healthy subjects acquired from a local hospital dataset, representing a typical clinical routine acquisition. In the third experiment, a hybrid training approach was employed, combining data of the HCP and local hospital datasets. Then, the best model was also tested in unseen DWIs of 10 epilepsy patients of the local hospital and 10 healthy subjects acquired on a scanner from another company. The outcomes of the third experiment demonstrated a notable enhancement in performance when contrasted with the preceding trials. Specifically, the short tracts within the local hospital dataset achieved Dice scores ranging between 0.60 and 0.65. Similar intervals were obtained with HCP data in the first experiment, and a substantial improvement compared to the scores between 0.37 and 0.50 obtained with the local hospital dataset at the same experiment. This improvement persisted when the method was applied to diverse scenarios, including different scanner acquisitions and epilepsy patients. These results indicate that combining datasets from different sources, coupled with resolution standardization strengthens the neural network ability to generalize predictions across a spectrum of datasets. Nevertheless, short tract segmentation performance is intricately linked to the training composition, to validation, and to testing data. Moreover, curved tracts have intricate structural nature, which adds complexities to their segmenting. Although the network training approach tested herein has provided promising results, caution must be taken when extrapolating its application to datasets acquired under distinct experimental conditions, even in the case of higher-quality data or analysis of long or short tracts.

Epigenetic control of adamantinomatous craniopharyngiomas.

INTRODUCTION: Studies addressing the methylation pattern in adamantinomatous craniopharyngioma (ACP) are lacking. OBJECTIVE: To identify methylation signatures in ACPs regarding clinical presentation and outcome. METHODS: Clinical and pathology data were collected from 35 ACP patients (54% male; 18.1 years [2-68]). CTNNB1 mutations and methylation profile (MethylationEPIC/Array-Illumina) were analyzed in tumoral DNA. Unsupervised machine learning analysis of this comprehensive methylome sample was achieved using hierarchical clustering and multi-dimensional scaling. Statistical associations between clusters and clinical features were achieved using Fisher's test and global biological process interpretations were aided by Gene Ontology enrichment analyses. RESULTS: Two clusters were revealed consistently by all unsupervised methods (ACP-1: n = 18; ACP-2: n = 17) with strong bootstrap statistical support. ACP-2 was enriched by CTNNB1 mutations (100% vs 56%, P = 0.0006), hypomethylated in CpG Island (CGI), non-CGI sites, and globally (P < 0.001), and associated with greater tumor size (24.1 vs 9.5cm3, P = 0.04). Enrichment analysis highlighted pathways on signaling transduction, transmembrane receptor, development of anatomical structures, cell-adhesion, cytoskeleton organization, and cytokine binding, and also cell-type specific biological processes as regulation of oligodendrocytes, keratinocyte, and epithelial cells differentiation. CONCLUSION: Two clusters of ACP patients were consistently revealed by unsupervised machine learning methods, being one of them significantly hypomethylated, enriched by CTNNB1 mutated ACPs, and associated with increased tumor size. Enrichment analysis reinforced pathways involved in tumor proliferation and in cell-specific tumoral microenvironment.

Volumetric analysis of the pharynx in patients with obstructive sleep apnea (OSA) treated with maxillomandibular advancement (MMA).

INTRODUCTION: Maxillomandibular advancement (MMA) has been reported to be the most effective surgical treatment of obstructive sleep apnea (OSA). Most reports about MMA aim to confirm the efficiency of this treatment modality, but few describe the anatomical changes produced in the pharynx by the surgery. Thus, the objective of the present investigation was to quantify the anatomical changes of the pharynx that occur in patients with OSA after MMA surgery using magnetic resonance (MR). METHODS: Twenty patients with a polysomnographic diagnosis of OSA participated in the study. All patients were submitted to image acquisition by MR performed during wakefulness. Polysomnography and MR were performed preoperatively and 6 months after MMA. Volume analysis (in cubic millimeters) was performed as the sum of the areas multiplied by their thickness, with no intervals between sections. The pharyngeal air space of the region between the hard palate and the base of the epiglottis was divided into a retropalatal (RP) region and a retrolingual (RL) region. RESULTS: Postoperative MR showed a mean volumetric increase of 26.72 % in the RP region and of 27.2 % in the RL region. DISCUSSION: MMA increases the air space of the pharynx by expanding the facial skeletal structure to which the soft tissues of the pharynx and tongue are fixed, with a consequent reduction of collapsibility in the presence of negative pressure during inspiration. This reduced possibility of pharyngeal collapse may contribute to the reduction of obstructive events.