Infrared spectral profiling of demyelinating activity in multiple sclerosis brain tissue.

Multiple sclerosis (MS) is a leading cause of non-traumatic disability in young adults. The highly dynamic nature of MS lesions has made them difficult to study using traditional histopathology due to the specificity of current stains. This requires numerous stains to track and study demyelinating activity in MS. Thus, we utilized Fourier transform infrared (FTIR) spectroscopy to generate holistic biomolecular profiles of demyelinating activities in MS brain tissue. Multivariate analysis can differentiate MS tissue from controls. Analysis of the absorbance spectra shows profound reductions of lipids, proteins, and phosphate in white matter lesions. Changes in unsaturated lipids and lipid chain length indicate oxidative damage in MS brain tissue. Altered lipid and protein structures suggest changes in MS membrane structure and organization. Unique carbohydrate signatures are seen in MS tissue compared to controls, indicating altered metabolic activities. Cortical lesions had increased olefinic lipid content and abnormal membrane structure in normal appearing MS cortex compared to controls. Our results suggest that FTIR spectroscopy can further our understanding of lesion evolution and disease mechanisms in MS paving the way towards improved diagnosis, prognosis, and development of novel therapeutics.

Delayed simvastatin treatment improves neurological recovery after cryogenic traumatic brain injury through downregulation of ELOVL1 by inhibiting mTOR signaling.

Statins are well-tolerated and widely available lipid-lowering medications with neuroprotective effects against traumatic brain injury (TBI). However, whether delayed statin therapy starting in the subacute phase promotes recovery after TBI is unknown. Elongation of the very long-chain fatty acid protein 1 (ELOVL1) is involved in astrocyte-mediated neurotoxicity, but its role in TBI and the relationship between ELOVL1 and statins are unclear. We hypothesized that delayed simvastatin treatment promotes neurological functional recovery after TBI by regulating the ELOVL1-mediated production of very long-chain fatty acids (VLCFAs). ICR male mice received daily intragastric administration of 1, 2 or 5mg/kg simvastatin on Days 1-14, 3-14, 5-14, or 7-14 after cryogenic TBI (cTBI). The results showed that simvastatin promoted motor functional recovery in a dose-dependent manner, with a wide therapeutic window of at least 7 days postinjury. Meanwhile, simvastatin inhibited astrocyte and microglial overactivation and glial scar formation, and increased total dendritic length, neuronal complexity and spine density on day 14 after cTBI. The up-regulation of ELOVL1 expression and saturated VLCFAs concentrations in the cortex surrounding the lesion caused by cTBI was inhibited by simvastatin, which was related to the inhibition of the mTOR signaling. Overexpression of ELOVL1 in astrocytes surrounding the lesion using HBAAV2/9-GFAP-m-ELOVL1-3xFlag-EGFP partially attenuated the benefits of simvastatin. These results showed that delayed simvastatin treatment promoted functional recovery and brain tissue repair after TBI through the downregulation of ELOVL1 expression by inhibiting mTOR signaling. Astrocytic ELOVL1 may be a potential target for rehabilitation after TBI.

PoLambRimetry: a multispectral polarimetric atlas of lamb brain.

Significance: Mueller matrix imaging (MMI) is a comprehensive form of polarization imaging useful for assessing structural changes. However, there is limited literature on the polarimetric properties of brain specimens, especially with multispectral analysis. Aim: We aim to employ multispectral MMI for an exhaustive polarimetric analysis of brain structures, providing a reference dataset for future studies and enhancing the understanding of brain anatomy for clinicians and researchers. Approach: A multispectral wide-field MMI system was used to measure six fresh lamb brain specimens. Multiple decomposition methods (forward polar, symmetric, and differential) and polarization invariants (indices of polarimetric purity and anisotropy coefficients) have been calculated to obtain a complete polarimetric description of the samples. A total of 16 labels based on major brain structures, including grey matter (GM) and white matter (WM), were identified. K -nearest neighbors classification was used to distinguish between GM and WM and validate the feasibility of MMI for WM identification. Results: As the wavelength increases, both depolarization and retardance increase, suggesting enhanced tissue penetration into deeper layers. Moreover, utilizing multiple wavelengths allowed us to track dynamic shifts in the optical axis of retardance within the brain tissue, providing insights into morphological changes in WM beneath the cortical surface. The use of multispectral data for classification outperformed all results obtained with single-wavelength data and provided over 95% accuracy for the test dataset. Conclusions: The consistency of these observations highlights the potential of multispectral wide-field MMI as a non-invasive and effective technique for investigating the brain's architecture.

Optical Transmission in Single-Layer Brain Tissues under Different Optical Source Types: Modelling and Simulation.

The human brain is a complex organ controlling daily activity. Present technique models have mostly focused on multi-layer brain tissues, which lack understanding of the propagation characteristics of various single brain tissues. To better understand the influence of different optical source types on individual brain tissues, we constructed single-layer brain models and simulated optical propagation using the Monte Carlo method. Based on the optical simulation results, sixteen optical source types had different optical energy distributions, and the distribution in cerebrospinal fluid had obvious characteristics. Five brain tissues (scalp, skull, cerebrospinal fluid, gray matter, and blood vessel) had the same set of the first three optical source types with maximum depth, while white matter had a different set of the first three optical source types with maximum depth. Each brain tissue had different optical source types with the maximum and minimum full width at half maximum. The study on single-layer brain tissues under different optical source types lays the foundation for constructing complex brain models with multiple tissue layers. It provides a theoretical reference for optimizing the selection of optical source devices for brain imaging.

Systematic analysis of constitutive models of brain tissue materials based on compression tests.

It's crucial to understand the biomechanical properties of brain tissue to comprehend the potential mechanisms of traumatic brain injury. This study, distinct from homogeneous models, integrates axonal coupling in both axial and transverse compressive experiments within a continuum mechanics framework to capture its intricate mechanical behaviors. Fresh porcine brains underwent unconfined compression at strain rates of 0.001/s and 0.1/s to 0.3 strain, allowing for a comprehensive statistical analysis of the directional, regional, and strain-rate-dependent mechanical properties of brain tissue. The established constitutive model, fitted to experimental data, delineates material parameters providing intuitive insights into the stiffness of gray/white matter isotropic matrices and neural fibers. Additionally, it predicts the mechanical performance of white matter matrix and axonal fibers under compressive loading. Results reveal that gray matter is insensitive to loading direction, exhibiting insignificant stiffness variations within regions. White matter, however, displays no significant differences in mechanical properties under axial and transverse loading, with an overall higher average stress than gray matter and a more pronounced strain-rate effect. Stress-strain curves indicate that, under axial compression, white matter axons primarily resist the load before transitioning to a matrix-dominated response. Under transverse loading, axonal fibers exhibit weaker resistance to lateral pressure. The mechanical behavior of brain tissue is highly dependent on loading rate, region, direction, and peak strain. This study, by combining experimentation with phenomenological modeling, elucidates certain phenomena, contributing valuable insights for the development of precise computational models.

An injectable biomimetic hydrogel adapting brain tissue mechanical strength for postoperative treatment of glioblastoma without anti-tumor drugs participation.

Adapting the mechanical strength between the implant materials and the brain tissue is crucial for the postoperative treatment of glioblastoma. However, no related study has been reported. Herein, we report an injectable lipoic acid­iron (LA-Fe) hydrogel (LFH) that can adapt to the mechanical strength of various brain tissues, including human brain tissue, by coordinating Fe3+ into a hybrid hydrogel of LA and its sodium salt (LANa). When LFH, which matches the mechanical properties of mouse brain tissue (337 ± 8.06 Pa), was injected into the brain resection cavity, the water content of the brain tissue was maintained at a normal level (77%). Similarly, LFH did not induce the activation or hypertrophy of glial astrocytes, effectively preventing brain edema and scar hyperplasia. Notably, LFH spontaneously degrades in the interstitial fluid, releasing LA and Fe3+ into tumor cells. The redox couples LA/DHLA (dihydrolipoic acid, reduction form of LA in cells) and Fe3+/Fe2+ would regenerate each other to continuously provide ROS to induce ferroptosis and activate immunogenic cell death. As loaded the anti-PDL1, anti-PDL1@LFH further enhanced the efficacy of tumor-immunotherapy and promoted tumor ferroptosis. The injectable hydrogel that adapted the mechanical strength of tissues shed a new light for the tumor postoperative treatment.

Impact of Intracranial Pressure and Invasive Cerebral Oxygenation Monitoring in Patients with Severe Traumatic Brain Injury: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Intracranial pressure (ICP) monitoring and monitoring of brain tissue oxygen (Pbto2) in addition to ICP have been used in the management of traumatic brain injury (TBI). However, the optimal monitoring method is inconclusive. We searched 4 databases with no language restrictions through January 2024 for peer-reviewed randomized controlled trials (RCTs) comparing ICP monitoring with combined Pbto2 and ICP monitoring in patients with traumatic brain injury. A favorable neurologic outcome was the primary outcome, and the secondary outcome was survival. Two reviewers screened manuscripts, extracted data, and assessed the risk of bias. We then performed a meta-analysis to assess efficacy using the Grading of Recommendations, Assessment, Development, and Evaluation working group approach. We included 5 trials comprising 512 patients. There was no difference in favorable neurologic outcome (risk ratio: 1.21; 95% confidence interval: 0.93, 1.58; I2: 45%; 5 RCTs: 512 patients; moderate certainty) and survival (risk ratio: 1.10; 95% confidence interval: 0.99, 1.21; I2: 13%; 5 RCTs: 512 patients; moderate certainty). We found no evidence that the combination of Pbto2 and ICP is more useful than ICP. The included RCTs are few and small, and further study is needed to draw conclusions.

Neurobehavioral toxicity of Cold plasma activated water following oral gavage in mice.

Cold plasma-activated water (PAW) is a novel technology that was recently used in biomedical research; Despite its potential, PAW's safety remains inadequately assessed. The study explores the impact of PAW on behavioral responses and brain tissue histopathology in mice. Ten-week-old female albino mice were divided into three groups each containing 10 mice (5 replicates, 2 mice/cage) and received either distilled water (DW), or distilled water exposed to cold atmospheric plasma (CAP) for 3 min (PAW-3), or 15 min (PAW-15) by oral gavage in a dose of 200 µL/mice (3 times/week) for four weeks. PAW exhibited altered physicochemical properties compared to DW. Mice exposed to PAW demonstrated reduced burrowing activity, marble burying ability, and novel object recognition compared to controls, indicating potential neurobehavioral alterations. PAW-treated groups displayed notable histological lesions in brain tissues, including nerve cell necrosis, vascular congestion, and Purkinje cell degeneration, confirming neurotoxic effects. Positive reactions for NF-κB and iNOS in brain tissues of PAW-treated mice corroborated the histopathological findings, suggesting neuroinflammation and oxidative stress. The study highlights the need for further investigation into PAW's safety profile and optimal treatment protocols to mitigate potential neurobehavioral toxicity in biomedical research.

Fabrication and Characterization of Brain Tissue Phantoms Using Agarose Gels for Ultraviolet Vision Systems.

Recreating cerebral tissue using a tissue-mimicking phantom is valuable because it provides a tool for studying physiological and biological processes related to tissues without the necessity of performing the study directly in the tissue or even in a patient. The reproduction of the optical properties allows investigation in areas such as imaging, optics, and ultrasound, among others. This paper presents a methodology for manufacturing agarose-based phantoms that mimic the optical characteristics of brain tissue using scattering and absorbing agents and proposes combinations of these agents to recreate the healthy brain tissue optical coefficients within the wavelength range of 350 to 500 nm. The results of the characterization of the manufactured phantoms propose ideal combinations of the used materials for their use in controlled environment experiments in the UV range, following a cost-effective methodology.

Correlation of brain tissue volume loss with inflammatory biomarkers IL1ß, P-tau, T-tau, and NLPR3 in the aging cognitively impaired population.

Background: Blood inflammatory biomarkers have emerged as important tools for diagnosing, assessing treatment responses, and predicting neurodegenerative diseases. This study evaluated the associations between blood inflammatory biomarkers and brain tissue volume loss in elderly people. Methods: This study included 111 participants (age 67.86 ± 8.29 years; 32 men and 79 women). A battery of the following blood inflammatory biomarkers was measured, including interleukin 1-beta (IL1ß), NACHT, LRR, and PYD domains-containing protein 3 (NLRP3), monomer Aß42 (mAß), oligomeric Aß42 (oAß), miR155, neurite outgrowth inhibitor A (nogo-A), phosphorylated tau (P-tau), and total tau (T-tau). Three-dimensional T1-weight images (3D T1WI) of all participants were prospectively obtained and segmented into gray matter and white matter to measure the gray matter volume (GMV), white matter volume (WMV), and gray-white matter boundary tissue volume (gwBTV). The association between blood biomarkers and tissue volumes was assessed using voxel-based and region-of-interest analyses. Results: GMV and gwBTV significantly decreased as the levels of IL1ß and T-tau increased, while no significant association was found between the level of P-tau and the three brain tissue volumes. Three brain tissue volumes were negatively correlated with the levels of IL1ß, P-tau, and T-tau in the hippocampus. Specifically, IL1ß and T-tau levels showed a distinct negative association with the three brain tissue volume losses in the hippocampus. In addition, gwBTV was negatively associated with the level of NLRP3. Conclusion: The observed association between brain tissue volume loss and elevated levels of IL1ß and T-tau suggests that these biomarkers in the blood may serve as potential biomarkers of cognitive impairment in elderly people. Thus, IL1ß and T-tau could be used to assess disease severity and monitor treatment response after diagnosis in elderly people who are at risk of cognitive decline.

Computational modeling and uncertainty prediction of hyperelastic constitutive responses of damaged brain tissue under different temperature and strain rates.

The effect of strain rate and temperature on the hyperelastic material stress-strain characteristics of the damaged porcine brain tissue is evaluated in this present work. The desired constitutive responses are obtained using the commercially available finite element (FE) tool ABAQUS, utilizing 8-noded brick elements. The model's accuracy has been verified by comparing the results from the previously published literature. Further, the stress-strain behavior of the brain tissue is evaluated by varying the damages at various strain rates and temperatures (13, 20, 27, and 37°C) under compression test. Additionally, the sensitivity analysis of the model is computed to check the effect of input parameters, that is, the temperature, strain rate, and damages on the material properties (shear modulus). The modeling and discussion sections enumerate the inclusive features and model capabilities.

Historical roots of modern neurosurgical cadaveric research practices: dissection, preservation, and vascular injection techniques.

Because of the complexity of the brain and its structures, anatomical knowledge is fundamental in neurosurgery. Anatomical dissection, body preservation, and vascular injection remain essential for training, teaching, and refining surgical techniques. This article explores the historical development of these practices and provides the contextual background of modern neurosurgical cadaveric brain models. Body preservation has ancient beginnings, evident in the Chinchorro mummifications and Egyptian embalming. However, brain preservation techniques for education were scarce until the beginning of the Renaissance in Europe. At the University of Bologna in the 13th century, occasional dissections were performed only in winter because of the lack of preservation techniques. Pope Sixtus IV's 1482 papal bull (official decree) formalized and expanded the use of dissection in medical education, leading to an explosion in anatomical studies. This surge brought advances in body preservation, such as soaking bodies in vinegar and distilled liquors. In subsequent centuries, Andreas Vesalius and Charles Bell advanced brain anatomical techniques and knowledge, combining novel illustrations and instruction. To better understand brain vasculature, Richard Lower developed vascular injection techniques using india ink and spirits of wine, leading to the 1664 description of the circle of Willis by Thomas Willis. In 1868, August Hofmann synthesized formaldehyde, markedly improving tissue preservation. Later, William Kruse introduced latex in 1939, and Sidney Sobin introduced silicone in 1965 for vascular studies. These advancements laid the foundation for modern neurosurgical cadaveric studies, many remaining relevant today.

Subject-specific atlas for automatic brain tissue segmentation of neonatal magnetic resonance images.

Developing advanced systems for 3D brain tissue segmentation from neonatal magnetic resonance (MR) images is vital for newborn structural analysis. However, automatic segmentation of neonatal brain tissues is challenging due to smaller head size and inverted T1/T2 tissue contrast compared to adults. In this work, a subject-specific atlas based technique is presented for segmentation of gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF) from neonatal MR images. It involves atlas selection, subject-specific atlas creation using random forest (RF) classifier, and brain tissue segmentation using the expectation maximization-Markov random field (EM-MRF) method. To increase the segmentation accuracy, different tissue intensity- and gradient-based features were used. Evaluation on 40 neonatal MR images (gestational age of 37-44 weeks) demonstrated an overall accuracy of 94.3% and an average Dice similarity coefficient (DSC) of 0.945 (GM), 0.947 (WM), and 0.912 (CSF). Compared to multi-atlas segmentation methods like SEGMA and EM-MRF with multiple atlases, our method improved accuracy by up to 4%, particularly in complex tissue regions. Our proposed method allows accurate brain tissue segmentation, a crucial step in brain magnetic resonance imaging (MRI) applications including brain surface reconstruction and realistic head model creation in neonates.

A perspective on epigenomic aging processes in the human brain and their plasticity in patients with mental disorders - a systematic review.

The debate surrounding nature versus nurture remains a central question in neuroscience, psychology, and in psychiatry, holding implications for both aging processes and the etiology of mental illness. Epigenetics can serve as a bridge between genetic predisposition and environmental influences, thus offering a potential avenue for addressing these questions. Epigenetic clocks, in particular, offer a theoretical framework for measuring biological age based on DNA methylation signatures, enabling the identification of disparities between biological and chronological age. This structured review seeks to consolidate current knowledge regarding the relationship between mental disorders and epigenetic age within the brain. Through a comprehensive literature search encompassing databases such as EBSCO, PubMed, and ClinicalTrials.gov, relevant studies were identified and analyzed. Studies that met inclusion criteria were scrutinized, focusing on those with large sample sizes, analyses of both brain tissue and blood samples, investigation of frontal cortex markers, and a specific emphasis on schizophrenia and depressive disorders. Our review revealed a paucity of significant findings, yet notable insights emerged from studies meeting specific criteria. Studies characterized by extensive sample sizes, analysis of brain tissue and blood samples, assessment of frontal cortex markers, and a focus on schizophrenia and depressive disorders yielded particularly noteworthy results. Despite the limited number of significant findings, these studies shed light on the complex interplay between epigenetic aging and mental illness. While the current body of literature on epigenetic aging in mental disorders presents limited significant findings, it underscores the importance of further research in this area. Future studies should prioritize large sample sizes, comprehensive analyses of brain tissue and blood samples, exploration of specific brain regions such as the frontal cortex, and a focus on key mental disorders. Such endeavors will contribute to a deeper understanding of the relationship between epigenetic aging and mental illness, potentially informing novel diagnostic and therapeutic approaches.

[Preliminary observation on the development and dynamic changes of chronic toxoplasmosis in mice].

OBJECTIVE: To investigate the development and dynamic changes of cysts in the brain of mice following infection with different forms of Toxoplasma gondii, so as to provide insights into for toxoplasmosis prevention and control. METHODS: ICR mice at ages of 6 to 8 weeks, each weighing 20 to 25 g, were intraperitoneally injected with tachyzoites of the T. gondii PRU strain at a dose of 1 × 105 tachyzoites per mouse, orally administered with cysts at a dose of 20 oocysts per mouse or oocysts at a dose of 200 oocysts per mouse for modeling chronic T. gondii infection in mice, and the clinical symptoms and survival of mice were observed post-infection. Mice were orally infected with T. gondii cysts at doses of 10 (low-dose group), 20 (medium-dose group), 40 cysts per mouse (high-dose group), and the effect of different doses of T. gondii infections on the number of cysts was examined in the mouse brain. Mice were orally administered with T. gondii cysts at a dose of 20 cysts per mouse, and grouped according to gender (female and male) and time points of infections (20, 30, 60, 90, 120, 150, 180 days post-infection), and the effects of gender and time points of infections on the number of cysts was examined in the mouse brain. In addition, mice were divided into the tachyzoite group (Group T), the first-generation cyst group (Group C1), the second-generation cyst group (Group C2), the third-generation cyst (Group C3) and the fourth-generation cyst group (Group C4). Mice in the Group T were intraperitoneally injected with T. gondii tachyzoites at a dose of 1 × 105 tachyzoites per mouse, and the cysts were collected from the mouse brain tissues 30 days post-infection, while mice in the Group C1 were orally infected with the collected cysts at a dose of 30 cysts per mouse. Continuous passage was performed by oral administration with cysts produced by the previous generation in mice, and the effect of continuous passage on the number of cysts was examined in the mouse brain. RESULTS: Following infection with T. gondii tachyzoites, cysts and oocysts in mice, obvious clinical symptoms were observed on days 6 to 13 and mice frequently died on days 7 to 12. The survival rates of mice were 67.0%, 87.0% and 53.0%, and the mean numbers of cysts were (516.0 ± 257.2), (1 203.0 ± 502.0) and (581.0 ± 183.1) in the mouse brain (F = 11.94, P < 0.01) on day 30 post-infection with T. gondii tachyzoites, cysts and oocysts, respectively, and the numbers of cysts in the brain tissues were significantly lower in mice infected with T. gondii tachyzoites and oocysts than in those infected with cysts (all P values < 0.01). The survival rates of mice were 87.0%, 87.0% and 60.0%, and the mean numbers of cysts were (953.0 ± 355.5), (1 084.0 ± 474.3) and (1 113.0 ± 546.0) in the mouse brain in the low-, medium- and high-dose groups on day 30 post-infection, respectively (F = 0.42, P > 0.05). The survival rates of male and female mice were 73.0% and 80.0%, and the mean numbers of cysts were (946.4 ± 411.4) and (932.1 ± 322.4) in the brain tissues of male and female mice, respectively (F = 1.63, P > 0.05). Following continuous passage, the mean numbers of cysts were (516.0 ± 257.2), (1 203.0 ± 502.0), (896.8 ± 332.3), (782.5 ± 423.9) and (829.2 ± 306.0) in the brain tissues of mice in the T, C1, C2, C3 and C4 groups, respectively (F = 4.82, P < 0.01), and the number of cysts was higher in the mouse brain in Group 1 than in Group T (P < 0.01). Following oral administration of 20 T. gondii cysts in mice, cysts were found in the moues brain for the first time on day 20 post-infection, and the number of cysts gradually increased over time, peaked on days 30 and 90 post-infection and then gradually decreased; however, the cysts were still found in the mouse brain on day 180 post-infection. CONCLUSIONS: There is a higher possibility of developing chronic T. gondii infection in mice following infection with cysts than with oocysts or tachyzoites and the most severe chronic infection is seen following infection with cysts. The number of cysts does not correlate with the severity of chronic T. gondii infection, and the number of cysts peaks in the mouse brain on days 30 and 90 post-infection.

Improving brain atrophy quantification with deep learning from automated labels using tissue similarity priors.

Brain atrophy measurements derived from magnetic resonance imaging (MRI) are a promising marker for the diagnosis and prognosis of neurodegenerative pathologies such as Alzheimer's disease or multiple sclerosis. However, its use in individualized assessments is currently discouraged due to a series of technical and biological issues. In this work, we present a deep learning pipeline for segmentation-based brain atrophy quantification that improves upon the automated labels of the reference method from which it learns. This goal is achieved through tissue similarity regularization that exploits the a priori knowledge that scans from the same subject made within a short interval must have similar tissue volumes. To train the presented pipeline, we use unlabeled pairs of T1-weighted MRI scans having a tissue similarity prior, and generate the target brain tissue segmentations in a fully automated manner using the fsl_anat pipeline implemented in the FMRIB Software Library (FSL). Tissue similarity regularization is enforced during training through a weighted loss term that penalizes tissue volume differences between short-interval scan pairs from the same subject. In inference, the pipeline performs end-to-end skull stripping and brain tissue segmentation from a single T1-weighted MRI scan in its native space, i.e., without performing image interpolation. For longitudinal evaluation, each image is independently segmented first, and then measures of change are computed. We evaluate the presented pipeline in two different MRI datasets, MIRIAD and ADNI1, which have longitudinal and short-interval imaging from healthy controls (HC) and Alzheimer's disease (AD) subjects. In short-interval scan pairs, tissue similarity regularization reduces the quantification error and improves the consistency of measured tissue volumes. In the longitudinal case, the proposed pipeline shows reduced variability of atrophy measures and higher effect sizes of differences in annualized rates between HC and AD subjects. Our pipeline obtains a Cohen's d effect size of d=2.07 on the MIRIAD dataset, an increase from the reference pipeline used to train it (d=1.01), and higher than that of SIENA (d=1.73), a well-known state-of-the-art approach. In the ADNI1 dataset, the proposed pipeline improves its effect size (d=1.37) with respect to the reference pipeline (d=0.80) and surpasses SIENA (d=1.33). The proposed data-driven deep learning regularization reduces the biases and systematic errors learned from the reference segmentation method, which is used to generate the training targets. Improving the accuracy and reliability of atrophy quantification methods is essential to unlock brain atrophy as a diagnostic and prognostic marker in neurodegenerative pathologies.

Exploration of the relationship between partial pressure of brain tissue oxygen and intracranial pressure.

Introduction: Partial pressure of brain tissue oxygen (PbtO2) has been shown to be a safe an effective monitoring modality to compliment intracranial pressure (ICP) monitoring. It is related to metabolic activity, disease severity and mortality. Research question: Understanding the complex relationship between PbtO2 and ICP for patients with traumatic brain injury will enable better clinical decision making beyond simple threshold treatment strategies. Material and methods: Patients with PbtO2 monitoring were identified from the BrainIT database, a multi-centre dataset, containing minute by minute PbtO2 and ICP readings. Missing data was imputed and a multi-level log-normal regression model with a compound symmetry correlation structure was built. This accounted for any increased correlation due to the repeated measurements. The model was adjusted for mean arterial pressure and the partial pressure of carbon dioxide. Non-linearity was assessed using analysis of deviance and trends using expected marginal means. Results: 11 subjects with over 82,000 readings were included. They had a median age of 38 (IQR: 37-47), 73% were male, a median length of stay of 11.8 (IQR: 6.6-19.7) days and a median extended Glasgow outcome scale of 7.00 (IQR: 5-8).There is a statistically significant (p < 0.001) non-linear effect of ICP on PbtO2. With an overall increase in PbtO2 of 5.2% (95% CI 4%-6.4%, p < 0.001) for a 10 mmHg increase in ICP below 22 mmHg and a decrease of 5.5% (95% CI 2.7%-8.3%, p=<0.001) in PbtO2 for a 10 mmHg increase in ICP above 22 mmHg. As well as a decrease of 40.9% (95% CI 2.3%-64.3%, p = 0.040) in PbtO2 per day in the intensive care unit. Discussion and conclusion: This model demonstrates that there is a significant non-linear relationship between ICP and PbtO2, however, this is a small heterogeneous cohort and further validation will be required.

Brain Metabolite Differences in Fetuses With Cytomegalovirus Infection: A Magnetic Resonance Spectroscopy Study.

BACKGROUND: Cytomegalovirus (CMV) is the most common intrauterine infection and may be associated with unfavorable outcomes. While some CMV-infected fetuses may show gross or subtle brain abnormalities on MRI, their clinical significance may be unclear. Conversely, normal development cannot be guaranteed in CMV-infected fetuses with normal MRI. PURPOSE: To assess brain metabolite differences in CMV-infected fetuses using magnetic resonance spectroscopy (MRS). STUDY TYPE: Retrospective. SUBJECTS: Out of a cohort of 149 cases, 44 with maternal CMV infection, amniocentesis results, and good-quality MRS were included. CMV-infected fetuses with positive polymerase chain reaction (PCR) (N = 35) were divided based on MRI results as follows: typical brain abnormalities (gross findings, N = 8), exclusive white matter hyperintense signal (WMHS) on T2-weighted images (subtle findings, N = 7), and normal MRI (N = 20). Uninfected fetuses (negative PCR) with normal MRI were included as controls (N = 9). FIELD STRENGTH: 3 T, T2-weighted half Fourier single-shot turbo spin-echo (HASTE), T2-weighted true fast imaging with steady-state free precession (TrueFISP), T1- and T2*-weighted fast low angle shot (FLASH), and 1H-MRS single-voxel point resolved spectroscopy (PRESS) sequences. ASSESSMENT: MRI findings were assessed by three radiologists, and metabolic ratios within the basal ganglia were calculated using LCModel. STATISTICAL TESTS: Analysis of covariance test with Bonferroni correction for multiple comparisons was used to compare metabolic ratios between groups while accounting for gestational age. A P-value <0.05 was deemed significant. RESULTS: MRS was successfully acquired in 63% of fetuses. Substantial agreement was observed between radiologists (Fleiss' kappa [k] = 0.8). Infected fetuses with gross MRI findings exhibited significantly reduced tNAA/tCr ratios (0.64 ± 0.08) compared with infected fetuses with subtle MRI findings (0.85 ± 0.19), infected fetuses with normal MRI (0.8 ± 0.14) and controls (0.81 ± 0.15). No other significant differences were detected (P ≥ 0.261). CONCLUSION: Reduced tNAA/tCr within the apparently normal brain tissue was detected in CMV-infected fetuses with gross brain abnormalities, suggesting extensive brain damage. In CMV-infected fetuses with isolated WMHS, no damage was detected by MRS. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 3.

Evaluating synthetic neuroimaging data augmentation for automatic brain tumour segmentation with a deep fully-convolutional network.

Gliomas observed in medical images require expert neuro-radiologist evaluation for treatment planning and monitoring, motivating development of intelligent systems capable of automating aspects of tumour evaluation. Deep learning models for automatic image segmentation rely on the amount and quality of training data. In this study we developed a neuroimaging synthesis technique to augment data for training fully-convolutional networks (U-nets) to perform automatic glioma segmentation. We used StyleGAN2-ada to simultaneously generate fluid-attenuated inversion recovery (FLAIR) magnetic resonance images and corresponding glioma segmentation masks. Synthetic data were successively added to real training data (n = 2751) in fourteen rounds of 1000 and used to train U-nets that were evaluated on held-out validation (n = 590) and test sets (n = 588). U-nets were trained with and without geometric augmentation (translation, zoom and shear), and Dice coefficients were computed to evaluate segmentation performance. We also monitored the number of training iterations before stopping, total training time, and time per iteration to evaluate computational costs associated with training each U-net. Synthetic data augmentation yielded marginal improvements in Dice coefficients (validation set +0.0409, test set +0.0355), whereas geometric augmentation improved generalization (standard deviation between training, validation and test set performances of 0.01 with, and 0.04 without geometric augmentation). Based on the modest performance gains for automatic glioma segmentation we find it hard to justify the computational expense of developing a synthetic image generation pipeline. Future work may seek to optimize the efficiency of synthetic data generation for augmentation of neuroimaging data.

Morphotype-specific calcium signaling in human microglia.

BACKGROUND: Key functions of Ca2+ signaling in rodent microglia include monitoring the brain state as well as the surrounding neuronal activity and sensing the danger or damage in their vicinity. Microglial Ca2+ dyshomeostasis is a disease hallmark in many mouse models of neurological disorders but the Ca2+ signal properties of human microglia remain unknown. METHODS: We developed a novel genetically-encoded ratiometric Ca2+ indicator, targeting microglial cells in the freshly resected human tissue, organotypically cultured tissue slices and analyzed in situ ongoing Ca2+ signaling of decades-old microglia dwelling in their native microenvironment. RESULTS: The data revealed marked compartmentalization of Ca2+ signals, with signal properties differing across the compartments and resident morphotypes. The basal Ca2+ levels were low in ramified and high in ameboid microglia. The fraction of cells with ongoing Ca2+ signaling, the fraction and the amplitude of process Ca2+ signals and the duration of somatic Ca2+ signals decreased when moving from ramified via hypertrophic to ameboid microglia. In contrast, the size of active compartments, the fraction and amplitude of somatic Ca2+ signals and the duration of process Ca2+ signals increased along this pathway.