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.

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.

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.

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.

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 oxygenation (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 four databases with no language restrictions through January 2024 for peer-reviewed randomized controlled trials (RTCs) comparing ICP monitoring with combined Pbto2 and ICP monitoring in patients with TBI. A favorable neurological 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 five trials comprising 522 patients. There was no difference in favorable neurological outcome (Risk Ratio [RR]: 1.16; 95% Confidence Interval [CI]: 0.98, 1.37; I2: 28%; 5 RCTs: 522 patients; moderate low certainty) and survival (RR: 1.10; 95% CI: 0.99, 1.21; I2: 13%; 5 RCTs: 522 patients; moderate low certainty). We found no evidence that the combination of Pbt2o and ICP is more useful than ICP. The included RCTs are few and small, and further study is needed to draw conclusions.

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.

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.

[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.

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.

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.

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.

Preservatives for postmortem brain tissue in biomechanical testing: A pilot study.

Postmortem human subject (PMHS) studies are essential to brain injury research in motor vehicle safety. However, postmortem deterioration reduces the similarity between postmortem test results and in vivo response in material testing of brain tissue and in biomechanical testing of the whole head. This pilot study explores the effect of potential preservatives on brain tissue breakdown to identify promising preservatives that warrant further investigation. To identify preservatives with potential to slow postmortem degradation, samples from an initial PMHS were refrigerated at 10°C to qualitatively compare tissue breakdown from 58 to 152 h postmortem after storage in candidate solutions. On brain tissue samples from a second PMHS, compressive stiffness was measured on six samples immediately after harvest for comparison to the stiffness of 23 samples that were stored at 10°C in candidate solutions for 24 h after harvest. The candidate solutions were artificial cerebrospinal fluid (ACSF) without preservatives; ACSF with a combination of antibiotics and antifungal agents; ACSF with added sodium bicarbonate; and ACSF with both the antibiotic/antifungal combination and sodium bicarbonate. Results were analyzed using multiple linear regression of specimen stiffness on harvest lobe and storage solution to investigate potential differences in tissue stiffness. Qualitative evaluation suggested that samples stored in a solution that contained both the antibiotic/antifungal combination and sodium bicarbonate exhibited less evidence of tissue breakdown than the samples stored without preservatives or with only one of those preservatives. In compression testing, samples tested immediately after harvest were significantly stiffer than samples tested after 24 h of storage at 10°C in ACSF (difference: -0.27 N/mm, 95% confidence interval (CI): -0.50, -0.05) or ACSF with antibiotics/antifungal agents (difference: -0.32 N/mm, 95% CI: -0.59, -0.04), controlling for harvest lobe. In contrast, the stiffness of samples tested after storage in either solution containing sodium bicarbonate was not significantly different from the stiffness of samples tested at harvest. There was no significant overall difference in the mean tissue stiffness between samples from the frontal and parietal lobes, controlling for storage solution. Given the importance of PMHS studies to brain injury research, any strategy that shows promise for helping to maintain in vivo brain material properties has the potential to improve understanding of brain injury mechanisms and tolerance to head injury and warrants further investigation. These pilot study results suggest that sodium bicarbonate has the potential to reduce the deterioration of brain tissue in biomechanical testing. The results motivate further evaluation of sodium bicarbonate as a preservative for biomechanical testing using additional test subjects, more comprehensive material testing, and evaluation under a broader set of test conditions including in whole-head testing. The effect of antibiotics and antifungal agents on brain tissue stiffness was minimal but may have been limited by the cold storage conditions in this study. Further exploration of the potential for microbial agents to preserve tissue postmortem would benefit from evaluation of the effects of storage temperature.

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.

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.

The Effects of Head Elevation on Intracranial Pressure, Cerebral Perfusion Pressure, and Cerebral Oxygenation Among Patients with Acute Brain Injury: A Systematic Review and Meta-Analysis.

BACKGROUND: Head elevation is recommended as a tier zero measure to decrease high intracranial pressure (ICP) in neurocritical patients. However, its quantitative effects on cerebral perfusion pressure (CPP), jugular bulb oxygen saturation (SjvO2), brain tissue partial pressure of oxygen (PbtO2), and arteriovenous difference of oxygen (AVDO2) are uncertain. Our objective was to evaluate the effects of head elevation on ICP, CPP, SjvO2, PbtO2, and AVDO2 among patients with acute brain injury. METHODS: We conducted a systematic review and meta-analysis on PubMed, Scopus, and Cochrane Library of studies comparing the effects of different degrees of head elevation on ICP, CPP, SjvO2, PbtO2, and AVDO2. RESULTS: A total of 25 articles were included in the systematic review. Of these, 16 provided quantitative data regarding outcomes of interest and underwent meta-analyses. The mean ICP of patients with acute brain injury was lower in group with 30° of head elevation than in the supine position group (mean difference [MD] - 5.58 mm Hg; 95% confidence interval [CI] - 6.74 to - 4.41 mm Hg; p < 0.00001). The only comparison in which a greater degree of head elevation did not significantly reduce the ICP was 45° vs. 30°. The mean CPP remained similar between 30° of head elevation and supine position (MD - 2.48 mm Hg; 95% CI - 5.69 to 0.73 mm Hg; p = 0.13). Similar findings were observed in all other comparisons. The mean SjvO2 was similar between the 30° of head elevation and supine position groups (MD 0.32%; 95% CI - 1.67% to 2.32%; p = 0.75), as was the mean PbtO2 (MD - 1.50 mm Hg; 95% CI - 4.62 to 1.62 mm Hg; p = 0.36), and the mean AVDO2 (MD 0.06 µmol/L; 95% CI - 0.20 to 0.32 µmol/L; p = 0.65).The mean ICP of patients with traumatic brain injury was also lower with 30° of head elevation when compared to the supine position. There was no difference in the mean values of mean arterial pressure, CPP, SjvO2, and PbtO2 between these groups. CONCLUSIONS: Increasing degrees of head elevation were associated, in general, with a lower ICP, whereas CPP and brain oxygenation parameters remained unchanged. The severe traumatic brain injury subanalysis found similar results.

Post-mortem changes of anisotropic mechanical properties in the porcine brain assessed by MR elastography.

Knowledge of the mechanical properties of brain tissue in vivo is essential to understanding the mechanisms underlying traumatic brain injury (TBI) and to creating accurate computational models of TBI and neurosurgical simulation. Brain white matter, which is composed of aligned, myelinated, axonal fibers, is structurally anisotropic. White matter in vivo also exhibits mechanical anisotropy, as measured by magnetic resonance elastography (MRE), but measurements of anisotropy obtained by mechanical testing of white matter ex vivo have been inconsistent. The minipig has a gyrencephalic brain with similar white matter and gray matter proportions to humans and therefore provides a relevant model for human brain mechanics. In this study, we compare estimates of anisotropic mechanical properties of the minipig brain obtained by identical, non-invasive methods in the live (in vivo) and dead animals (in situ). To do so, we combine wave displacement fields from MRE and fiber directions derived from diffusion tensor imaging (DTI) with a finite element-based, transversely-isotropic nonlinear inversion (TI-NLI) algorithm. Maps of anisotropic mechanical properties in the minipig brain were generated for each animal alive and at specific times post-mortem. These maps show that white matter is stiffer, more dissipative, and more anisotropic than gray matter when the minipig is alive, but that these differences largely disappear post-mortem, with the exception of tensile anisotropy. Overall, brain tissue becomes stiffer, less dissipative, and less mechanically anisotropic post-mortem. These findings emphasize the importance of testing brain tissue properties in vivo. Statement of Significance: In this study, MRE and DTI in the minipig were combined to estimate, for the first time, anisotropic mechanical properties in the living brain and in the same brain after death. Significant differences were observed in the anisotropic behavior of brain tissue post-mortem. These results demonstrate the importance of measuring brain tissue properties in vivo as well as ex vivo, and provide new quantitative data for the development of computational models of brain biomechanics.

Microglial proliferation and astrocytic protein alterations in the human Huntington's disease cortex.

Huntington's disease (HD) is a neurodegenerative disorder that severely affects the basal ganglia and regions of the cerebral cortex. While astrocytosis and microgliosis both contribute to basal ganglia pathology, the contribution of gliosis and potential factors driving glial activity in the human HD cerebral cortex is less understood. Our study aims to identify nuanced indicators of gliosis in HD which is challenging to identify in the severely degenerated basal ganglia, by investigating the middle temporal gyrus (MTG), a cortical region previously documented to demonstrate milder neuronal loss. Immunohistochemistry was conducted on MTG paraffin-embedded tissue microarrays (TMAs) comprising 29 HD and 35 neurologically normal cases to compare the immunoreactivity patterns of key astrocytic proteins (glial fibrillary acidic protein, GFAP; inwardly rectifying potassium channel 4.1, Kir4.1; glutamate transporter-1, GLT-1; aquaporin-4, AQP4), key microglial proteins (ionised calcium-binding adapter molecule-1, IBA-1; human leukocyte antigen (HLA)-DR; transmembrane protein 119, TMEM119; purinergic receptor P2RY12, P2RY12), and indicators of proliferation (Ki-67; proliferative cell nuclear antigen, PCNA). Our findings demonstrate an upregulation of GFAP+ protein expression attributed to the presence of more GFAP+ expressing cells in HD, which correlated with greater cortical mutant huntingtin (mHTT) deposition. In contrast, Kir4.1, GLT-1, and AQP4 immunoreactivity levels were unchanged in HD. We also demonstrate an increased number of IBA-1+ and TMEM119+ microglia with somal enlargement. IBA-1+, TMEM119+, and P2RY12+ reactive microglia immunophenotypes were also identified in HD, evidenced by the presence of rod-shaped, hypertrophic, and dystrophic microglia. In HD cases, IBA-1+ cells contained either Ki-67 or PCNA, whereas GFAP+ astrocytes were devoid of proliferative nuclei. These findings suggest cortical microgliosis may be driven by proliferation in HD, supporting the hypothesis of microglial proliferation as a feature of HD pathophysiology. In contrast, astrocytes in HD demonstrate an altered GFAP expression profile that is associated with the degree of mHTT deposition.

Letter to editor: Brain tissue oxygen partial pressure monitoring and prognosis of patients with traumatic brain injury: a meta-analysis of published cases.

This critique evaluates a letter to the editor discussing the role of brain tissue oxygen partial pressure (PbtO2) monitoring in the prognosis of patients with traumatic brain injury (TBI). The meta-analysis aims to synthesize existing evidence, highlighting the potential of PbtO2 monitoring as an early indicator of cerebral hypoxia and its correlation with improved patient outcomes. Despite these promising findings, the analysis is constrained by significant methodological variability among the included studies, potential publication bias, and the practical challenges of implementing PbtO2 monitoring widely. The letter emphasizes the need for standardized protocols and further research to solidify the clinical utility of PbtO2 monitoring and integrate it with other monitoring strategies for comprehensive TBI management.