The collection and processing of human brain tissue for research

To further understand the neuroanatomy, neurochemistry and neuropathology of the normal and diseased human brain, it is essential to have access to human brain tissue where the biological and chemical nature of the tissue is optimally preserved. We have established a human brain bank where brain tissue is optimally processed and stored in order to provide a resource to facilitate neuroscience research of the human brain in health and disease. A donor programme has been established in consultation with the community to provide for the post-mortem donation of brain tissue to the brain bank. We are using this resource of human brain tissue to further investigate the basis of normal neuronal functioning in the human brain as well as the mechanisms of neuronal dysfunction and degeneration in neurodegenerative diseases. We have established a protocol for the preservation of post-mortem adult human brain tissue firstly by snap-freezing unfixed brain tissue and secondly by chemical fixation and then storage of this tissue at -80 degrees C in a human brain bank. Several research techniques such as receptor autoradiography, DNA and RNA analysis, are carried out on the unfixed tissue and immunohistochemical and histological analysis is carried out on the fixed human tissue. Comparison of tissue from normal control cases and from cases with neurodegenerative disorders is carried out in order to document the changes that occur in the brain in these disorders and to further investigate the underlying pathogenesis of these devastating neurological diseases.     

Tryptophan is a marker of human postmortem brain tissue quality

Postmortem human brain tissue is widely used in neuroscience research, but use of tissue originating from different brain bank centers is considered inaccurate because of possible heterogeneity in sample quality. There is thus a need for well-characterized markers to assess the quality of postmortem brain tissue. Toward this aim, we determined tryptophan (TRP) concentrations, phosphofructokinase-1 and glutamate decarboxylase activities in 119 brain tissue samples. These neurochemical parameters were tested in samples from autopsied individuals, including control and pathological cases provided by 10 different brain bank centers. Parameters were assessed for correlation with agonal state, postmortem interval, age and gender, brain region, preservation and freezing methods, storage conditions and storage time, RNA integrity, and tissue pH value. TRP concentrations were elevated significantly ( p  = 0.045) with increased postmortem interval; which might indicate increased protein degradation. Therefore, TRP concentration might be one useful and convenient marker for estimating the quality of human postmortem brain tissue.     

Recognition of brain tumors in MRI images using texture analysis

ObjectivesBrain neoplasms or intracranial tumors, which are more common in older adults, can affect individuals of any age including pediatric and children. Exposure to carcinogenic agents including ionizing radiation and family history is one of the main causes of the disease. Early diagnosis is crucial to avoid prolonged. patients' suffering. The aim of the study was to efficiently recognize the brain tumors from the other brain tissues which include grey and white matter as well as cerebrospinal fluid (CSF).Materials and methodsThis study was performed using axial, sagittal and coronal views for fifty brain tumor patients randomly selected from a set of 200 patients, with a “control” set consisting of images showing no sign of disease; and the “test” brain MRI images for patients diagnosed with brain tumor. The study includes both genders with age ranging from 18 years to 83 years old, (56.5 ± 17.2). The brain images were acquired using a standard head coil Philips Intera 1.5 Tesla machine (USA). The thickness of each section in the entire sequence was 8 mm. Acquisition of T2-weighted and T1-weighted were performed. Interactive Data Language software was used to analyze the data.ResultsThe results of this study showed that: the overall accuracy of classification process was 94.8%, and for the tumor; the sensitivity was 97.3%. White matter and grey matter showed a classification accuracy of 95.7% and 89.7% and for CSF the accuracy was 94.3%.ConclusionThe results showed that brain tumor can be classified successfully and delineated using texture analysis with minimum efforts and with high accuracy for brain tumors.     

Supply and use of human tissue for research purposes: survey of BATB affiliated tissue banks

This paper describes a survey undertaken to identify the extent of supply and use of human tissue in research by BATB affiliated tissue banks. Approximately one third of tissue banks registered with the BATB are currently supplying samples that are found to be unsuitable for clinical use, for research. These banks all obtain consent for research and all supply tissue for in-house research. Some tissue is transferred to other public and commercial institutions. A harmonised network approach is proposed as the way forward to meet the increasing demand for human tissue in research.     

Twenty-first century brain banking: practical prerequisites and lessons from the past: the experience of New York Brain Bank,Taub Institute,Columbia University

Generally accepted methods for processing postmortem brains are lacking, despite the efforts of pioneers in the field, and the growing awareness of the importance of brain banking for investigating the pathogenesis of illnesses unique to humans. Standardizing methods requires compromises, institutional or departmental mindset promoting collaboration, and the willingness to share ideas, information, and samples. A sound balance between competition and institutional interests is needed to best fulfill the tasks entrusted to health care institutions. Thus, a potentially widely accepted protocol design involves tradeoffs. We successfully integrated brain banking within the operation of the department of pathology. We reached a consensus whereby a brain can be utilized for diagnosis, research, and teaching. Thus, routing brains away from residency programs is avoided. The best diagnostic categorization possible is being secured and the yield of samples for research maximized. Thorough technical details pertaining to the actual processing of brains donated for research were recently published. Briefly, one-half of each brain is immersed in formalin for performing the neuropathologic evaluation, which is combined with the teaching task. The contralateral half is extensively dissected at the fresh state to obtain samples ready for immediate disbursement once categorized diagnostically. The samples are tracked electronically, which is crucial. This important tracking system is described separately in this issue. This report focuses on key lessons learned over the past 25 years of brain banking including successful solutions to originally unforeseen problems.     

Constitutive modelling of brain tissue: Experiment and theory

Recent developments in computer-integrated and robot-aided surgery—in particular, the emergence of automatic surgical tools and robots—as well as advances in virtual reality techniques, call for closer examination of the mechanical properties of very soft tissues (such as brain, liver, kidney, etc.). The ultimate goal of our research into the biomechanics of these tissues is the development of corresponding, realistic mathematical models. This paper contains experimental results of in vitro, uniaxial, unconfined compression of swine brain tissue and discusses a single-phase, non-linear, viscoelastic tissue model. The experimental results obtained for three loading velocities, ranging over five orders of magnitude, are presented. The applied strain rates have been much lower than those applied in previous studies, focused on injury modelling. The stress-strain curves are concave upward for all compression rates containing no linear portion from which a meaningful elastic modulus might be determined. The tissue response stiffened as the loading speed increased, indicating a strong stress-strain rate dependence. The use of the single-phase model is recommended for applications in registration, surgical operation planning and training systems as well as a control system of an image-guided surgical robot. The material constants for the brain tissue are evaluated. Agreement between the proposed theoretical model and experiment is good for compression levels reaching 30% and for loading velocities varying over five orders of magnitude.     

Influence of structure on the tissue dynamics of the human soleus muscle observed in MRI studies during isometric contractions

This article investigates how the internal structure of muscle and its relationship with tendon and even skeletal structures influence the translation of muscle fiber contractions into movement of a limb. Reconstructions of the anatomy of the human soleus muscle from the Visible Human Dataset (available from the National Library of Medicine), magnetic resonance images (MRI), and cadaver studies revealed a complex 3D connective tissue structure populated with pennate muscle fibers. The posterior aponeurosis and the median septum of the soleus form the insertion of the muscle and are continuous with the Achilles tendon. The distal extremities of the pennate muscle fibers attach to these structures. The anterior aponeurosis is located intramuscularly, between the posterior aponeurosis and the median septum. It forms the origin of the muscle and contacts the proximal extremities of the soleus muscle fibers. MRI measurements of in vivo tissue velocities during isometric contractions (20% and 40% maximum voluntary contractions) revealed a similarly complex 3D distribution of tissue movements. The distribution of velocities was similar to the distribution of major connective tissue structures within the muscle. During an isometric contraction, muscle fiber contractions move the median septum and posterior aponeurosis proximally, relative to the anterior aponeurosis. The pennate arrangement of muscle fibers probably amplifies muscle fiber length changes but not sufficiently to account for the twofold difference in muscle fiber length changes relative to excursion of the calcaneus. The discrepancy may be accounted for by an additional gain mechanism operating directly on the Achilles tendon by constraining the posterior movement of the tendon, which would otherwise occur due to the increasingly posterior location of the calcaneus in plantarflexeion.     

成人急性播散性脑脊髓炎脑部的MRI 表现及临床分析

目的:探讨成人急性播散性脑脊髓炎(ADEM)的脑部MRI表现特点。方法:回顾性分析符合临床诊断标准的成人ADEM患者8例。8例均进行MRI平扫,7例进行增强扫描。采用自旋回波(SE)序列、快速自旋回波(FSE)序列、FLAIR序列及EPI序列扫描。常规行矢状面、横断面及冠状面扫描。结果:(1)病变主要位于双侧侧脑室周围及额、顶、颞、枕皮质下白质区,主要特点为多发且分布大部分不对称,双侧侧脑室旁白质可见"垂直脱髓鞘征",病灶部分呈对称分布,同时累及丘脑、脑干、胼胝体、小脑白质或大脑皮质。4例累及双侧丘脑,病灶呈对称性分布。(2)8例病变信号均以长及略长TW1信号、长TW2信号为主,3例在病变中心可见更长TW1、更长TW2信号。(3)7例平扫异常信号增强扫描均可见不同程度异常强化,急性期病灶多呈点、斑片状、环形、类圆形及索条状强化。结论:ADEM脑部的MRI表现具有一定特征性,MRI具有重要诊断价值。     

Dielectric properties of human brain tissue measured less than 10 h postmortem at frequencies from 800 to 2450 MHz

The dielectric properties of gray matter in the frequency range of 800-2450 MHz were measured on 20 human brains immediately after excision, less than 10 h after death. The brains were obtained during autopsy of 10 male and 10 female humans who died at ages between 47.5 and 87.5 years [70.4 +/- 9.8 years, mean +/- standard deviation (SD)]. The tissue temperature at the measurement sites ranged between 18 and 25 degrees C (21.35 +/- 1.6 degrees C, mean +/- SD). On each brain, four specific locations on the temporal lobe were measured on the right and left sides, i.e., 160 different measurements of the dielectric properties were performed. The dielectric probe was placed on the intact arachnoid on a gyrus in the selected area. The measurements yielded a mean value (+/-SD) of gray matter equivalent conductivity of 1.13 +/- 0.12 and 2.09 +/- 0.16 S/m at 800 and 2450 MHz, respectively. The mean value of measured relative permittivity was 58.2 +/- 3.3 and 54.7 +/- 3.3 at 800 and 2450 MHz, respectively. Taking into account a positive temperature coefficient of equivalent conductivity, these measurements indicate that the equivalent conductivity of human gray matter at body temperature is somewhat higher than today's generally accepted value, which is based on measurements on animal tissue and excised samples of human tissue measured more than 24 h postmortem.     

Effects of different correlation metrics and preprocessing factors on small-world brain functional networks: a resting-state functional MRI study

Graph theoretical analysis of brain networks based on resting-state functional MRI (R-fMRI) has attracted a great deal of attention in recent years. These analyses often involve the selection of correlation metrics and specific preprocessing steps. However, the influence of these factors on the topological properties of functional brain networks has not been systematically examined. Here, we investigated the influences of correlation metric choice (Pearson's correlation versus partial correlation), global signal presence (regressed or not) and frequency band selection [slow-5 (0.01-0.027 Hz) versus slow-4 (0.027-0.073 Hz)] on the topological properties of both binary and weighted brain networks derived from them, and we employed test-retest (TRT) analyses for further guidance on how to choose the "best" network modeling strategy from the reliability perspective. Our results show significant differences in global network metrics associated with both correlation metrics and global signals. Analysis of nodal degree revealed differing hub distributions for brain networks derived from Pearson's correlation versus partial correlation. TRT analysis revealed that the reliability of both global and local topological properties are modulated by correlation metrics and the global signal, with the highest reliability observed for Pearson's-correlation-based brain networks without global signal removal (WOGR-PEAR). The nodal reliability exhibited a spatially heterogeneous distribution wherein regions in association and limbic/paralimbic cortices showed moderate TRT reliability in Pearson's-correlation-based brain networks. Moreover, we found that there were significant frequency-related differences in topological properties of WOGR-PEAR networks, and brain networks derived in the 0.027-0.073 Hz band exhibited greater reliability than those in the 0.01-0.027 Hz band. Taken together, our results provide direct evidence regarding the influences of correlation metrics and specific preprocessing choices on both the global and nodal topological properties of functional brain networks. This study also has important implications for how to choose reliable analytical schemes in brain network studies.     

中国古人类颅内模及脑演化研究进展

颅内模保存有脑表面的形态结构,是脑演化研究的直接证据。中国最早复原和研究的颅内模来自20世纪20年代北京周口店遗址发现的3号猿人头骨;此后虽然中国境内也相继发现了一些古人类的头骨化石,但由于古人类标本非常珍贵,不允许对其进行实体解剖,加上多数头骨破碎或者内部附有地层胶结物,导致颅内模无法成功复原。受技术水平及研究手段的限制,研究者一般只是侧重于化石外表形态结构的研究。高分辨率工业CT和3D软件的应用,可以在不损坏标本的情况下,虚拟复原出化石的内部解剖结构,使得一些重要的古人类化石标本的颅内模被复原出来,促进了脑演化的研究。近年来,本文第一作者采用新技术、新方法复原了南京直立人、柳江人等一些重要的中国古人类头骨的颅内模,通过对其颅容量、脑沟回特征、脑不对称性、脑表面的动、静脉血管压迹、各脑叶的大小、形状及比例的研究,获取了中国古人类脑形态特征变化的数据,为探讨东亚地区古人类的演化提供了参考信息。     

A Hybrid CNN-SVM Threshold Segmentation Approach for Tumor Detection and Classification of MRI Brain Images

ObjectiveIn this research paper, the brain MRI images are going to classify by considering the excellence of CNN on a public dataset to classify Benign and Malignant tumors.Materials and MethodsDeep learning (DL) methods due to good performance in the last few years have become more popular for Image classification. Convolution Neural Network (CNN), with several methods, can extract features without using handcrafted models, and eventually, show better accuracy of classification. The proposed hybrid model combined CNN and support vector machine (SVM) in terms of classification and with threshold-based segmentation in terms of detection.ResultThe findings of previous studies are based on different models with their accuracy as Rough Extreme Learning Machine (RELM)-94.233%, Deep CNN (DCNN)-95%, Deep Neural Network (DNN) and Discrete Wavelet Autoencoder (DWA)-96%, k-nearest neighbors (kNN)-96.6%, CNN-97.5%. The overall accuracy of the hybrid CNN-SVM is obtained as 98.4959%.ConclusionIn today's world, brain cancer is one of the most dangerous diseases with the highest death rate, detection and classification of brain tumors due to abnormal growth of cells, shapes, orientation, and the location is a challengeable task in medical imaging. Magnetic resonance imaging (MRI) is a typical method of medical imaging for brain tumor analysis. Conventional machine learning (ML) techniques categorize brain cancer based on some handicraft property with the radiologist specialist choice. That can lead to failure in the execution and also decrease the effectiveness of an Algorithm. With a brief look came to know that the proposed hybrid model provides more effective and improvement techniques for classification.     

Comparison of porcine brain mechanical properties to potential tissue simulant materials in quasi-static and sinusoidal compression

In both finite element and physical surrogate models of head blast injury, accurate material properties of the brain and/or tissue simulants are necessary to ensure biofidelity in predicted response. Thus, there is a need for experimental comparisons between tissue and simulant materials under the same experimental conditions. This study compares the response of porcine brain tissue and a variety of brain tissue simulants in quasi-static and sinusoidal compression tests. Fresh porcine brain tissue was obtained from a local abattoir and tested within 4 h post mortem. Additionally, the effect of post mortem time was investigated by comparing samples stored at room temperature and stored frozen (−18 °C), at various time intervals. The brain tissue simulants tested were bovine gelatin (3%, 5%, and 10% concentration), agarose gelatin (e0.4%, 0.6%, 0.8% concentration), and Sylgard 527. The experiments were performed using a DMA apparatus (TA Instruments Q800). The quasi-static compression data were fit to Ogden hyperelastic functions so that parameters could be compared. It was found that bovine gelatin at 3% and 5% concentration demonstrated the closest response to brain tissue in quasi-static compression. Conversely, in sinusoidal compression, the agarose gel and Sylgard 527 were found to be in closer agreement with the tissue, than bovine gel. In terms of post mortem time and storage, there was no statistically significant difference detected in the response of tissue samples after 48 h, regardless of storage method. However, samples stored at room temperature after 48 h appeared to demonstrate a reduction in stiffness.     

Dysregulated mitochondrial genes and networks with drug targets in postmortem brain of patients with posttraumatic stress disorder (PTSD) revealed by human mitochondria-focused cDNA microarrays

Posttraumatic stress disorder (PTSD) is associated with decreased activity in the dorsolateral prefrontal cortex (DLPFC), the brain region that regulates working memory and preparation and selection of fear responses. We investigated gene expression profiles in DLPFC Brodmann area (BA) 46 of postmortem patients with (n=6) and without PTSD (n=6) using human mitochondria-focused cDNA microarrays. Our study revealed PTSD-specific expression fingerprints of 800 informative mitochondria-focused genes across all of these 12 BA46 samples, and 119 (+/->1.25, p<0.05) and 42 (+/->1.60, p<0.05) dysregulated genes between the PTSD and control samples. Quantitative RT-PCR validated the microarray results. These fingerprints can essentially distinguish the PTSD DLPFC BA46 brains from controls. Of the 119 dysregulated genes (+/-> or =125%, p<0.05), the highest percentages were associated with mitochondrial dysfunction (4.8%, p=6.61 x 10(-6)), oxidative phosphorylation (3.8%, p=9.04 x 10(-4)), cell survival-apoptosis (25.2%, p<0.05) and neurological diseases (23.5%, p<0.05). Fifty (50) dysregulated genes were present in the molecular networks that are known to be involved in neuronal function-survival and contain 7 targets for neuropsychiatric drugs. Thirty (30) of the dysregulated genes are associated with a number of neuropsychiatric disorders. Our results indicate mitochondrial dysfunction in the PTSD DLPFC BA46 and provide the expression fingerprints that may ultimately serve as biomarkers for PTSD diagnosis and the drugs and molecular targets that may prove useful for development of remedies for prevention and treatment of PTSD.     

Characterization and localization of 3H-arginine8-vasopressin binding to rat kidney and brain tissue

Anatomic, behavioral and pharmacologic evidence suggests that arginine8-vasopressin (AVP) serves as a CNS neurotransmitter or neuromodulator. We have characterized AVP binding to membrane and tissue slice preparations from brain and kidney, and examined the anatomical distribution of these binding sites. Conditions for the binding assay were optimized using kidney medullary tissue. Binding of 3H-AVP (S.A. = 30-51 Ci/mmol, NEN) to brain and kidney membranes and tissue slices was saturable, temperature dependent, linearly related to protein concentration (or number of tissue slices), reversible, and specific since the ability of cold AVP to displace 3H-AVP from binding was greater than oxytocin and other related peptide fragments. Autoradiographic localization of 3H-AVP binding was restricted to kidney medullary tissue. In brain tissue, 3H-AVP binding was found to occur in concentrated foci. Brainstem areas such as the nucleus tractus solitarius (NTS) showed a high density of AVP binding sites. Since local injections of AVP into the NTS have been shown to influence blood pressure, the present study presents the first anatomical evidence for the presence of AVP specific binding sites which might mediate this effect.     

Multispectral optoacoustic and MRI coregistration for molecular imaging of orthotopic model of human glioblastoma

Multi‐modality imaging methods are of great importance in oncologic studies for acquiring complementary information, enhancing the efficacy in tumor detection and characterization. We hereby demonstrate a hybrid non‐invasive in vivo imaging approach of utilizing magnetic resonance imaging (MRI) and Multispectral Optoacoustic Tomography (MSOT) for molecular imaging of glucose uptake in an orthotopic glioblastoma in mouse. The molecular and functional information from MSOT can be overlaid on MRI anatomy via image coregistration to provide insights into probe uptake in the brain, which is verified by ex vivo fluorescence imaging and histological validation.

In vivo MSOT and MRI imaging of an orthotopic glioma mouse model injected with IRDye800‐2DG. Image coregistration between MSOT and MRI enables multifaceted (anatomical, functional, molecular) information from MSOT to be overlaid on MRI anatomy images to derive tumor physiological parameters such as perfusion, haemoglobin and oxygenation.     

Effect of antemortem and postmortem factors on [3H]MK-801 binding in the human brain: transient elevation during early childhood

The effect of a number of antemortem and postmortem factors on [3H]MK-801 binding was investigated under equilibrium conditions in the frontal cortex of human brains of 38 controls. Binding values transiently increased during the early postnatal period reaching a maximum at the age of about 2 years. After age 10 years [3H]MK-801 binding sites disappeared at 5.7% per decade. The storage time of brain tissue had a reducing effect on these binding sites. There was no effect of gender, brain weight or postmortem time interval and the binding sites were bilaterally symmetrically distributed in the frontal cortex.     

Radiation-modifying abilities of Nigella sativa and Thymoquinone on radiation-induced nitrosative stress in the brain tissue

To investigate Nigella sativa oil (NSO) and Thymoquinone (TQ) for their antioxidant effects on the brain tissue of rats exposed to ionizing radiation.Fifty-four male albino Wistar rats, divided into six groups, were designed as group I (normal control group) did not receive NSO, TQ or irradiation; group II (control group of TQ) received dimethyl sulfoxide and sham irradiation; group III (control group of NSO) received saline and sham irradiation; group IV (irradiation plus NSO group) received both 5 Gray of gamma irradiation to total cranium and NSO; group V (irradiation plus TQ group) received both irradiation and TQ; group VI (irradiation alone group) received irradiation plus saline. Alterations in nitric oxide (NO) and peroxynitrite (ONOO⁻) levels, and nitric oxide synthase (NOS) enzyme activity were measured by biochemical methods in homogenized brain tissue of rats.Levels of NO and ONOO⁻, and enzyme activity of NOS in brain tissue of the rats treated with NSO or TQ were found to be lower than in received IR alone (p < 0.002)Nigella sativa oil (NSO) and its active component, TQ, clearly protect brain tissue from radiation-induced nitrosative stress.     

Hippocampal electrical activity and gamma-aminobutyrate metabolism in brain tissue following administration of homocysteine

Abstract: The concentration of γ-aminobutyrate (GABA) and the activity of glutamate decarboxylase and GABA-transaminase were measured in extracts of mouse brain before the onset and during the course of generalized seizures induced by systemic administration of homocysteine thiolactone. The results indicate that whole brain GABA metabolism is unaffected by subconvulsive and convulsive doses of homocysteine at all stages of the generalized seizure. Electroencephalographic monitoring of rat brain electrical activity via hippocampal electrode implantation allowed the course of homocysteine-induced seizures to be followed and afforded a means of quantifying such seizures.