New laser techniques for diagnosis and treatment of deep-seated brain lesions

The five years survival rate of deep-seated malignant brain tumors after surgery/radiotherapy is virtually 100% mortality. Special problems include: (1) lesions often present late; (2) position: lesions overlies vital structures, so complete surgical/radiotherapy lesion destruction can damage vital brain-stem functions; and (3) difficulty in differentiating normal brain from malignant lesions. This study aimed to use the unique properties of the laser: (a) to minimize damage during surgical removal of deep-seated brain lesions by operating via fine optic fibers; and (b) to employ the propensity of certain lasers for absorption of (nontoxic) dyes and absorption and induction of fluorescence in some brain substances, to differentiate borders of malignant and normal brain, for more complete tumor removal. A fine laser endoscopic technique was devised for removal of brain lesions, which minimized thermal damage and shock waves. A compatible endoscopic fluoroscopic laser technique was developed to differentiate brain tumor from normal brain.     

Detection of toxoplasmic lesions in mouse brain by USPIO-enhanced magnetic resonance imaging

The objective of this study was to examine the feasibility of detecting toxoplasmic brain lesions in a mouse model of cerebral toxoplasmosis by ultrasmall superparamagnetic particles of iron oxide (USPIO)-enhanced magnetic resonance imaging (MRI). Toxoplasmosis encephalitis was induced in Kunming mice by intracerebral injection of Toxoplasma gondii tachyzoites. T₂- and T₂*-weighted MRI was performed 1, 3, 4, 5 and 6 days after infection before USPIO injection; immediately after USPIO injection; and 24 h later. A comparison of USPIO enhancement and Gd-DTPA enhancement was made in three toxoplasmic mice 4 days after infection. Hematoxylin and eosin staining and Prussian blue staining were performed to detect inflammatory reactions and presence of iron in and around the toxoplasmic brain lesions. Nonenhanced T₂-/T₂*-weighted imaging detected few abnormalities in the brain up to 5 days. Most mice developed prominent hydrocephalus at 6 days. Gd-DTPA-enhanced imaging showed prominent enhancement of the cerebral ventricles but revealed only few space-occupying lesions in the parenchyma. USPIO-enhanced T₂*-weighted imaging showed improved detection of toxoplasmic brain lesions that were invisible to nonenhanced T₂-/T₂*-weighted imaging and gadolinium-enhanced imaging. Most of the enhancing lesions showed nodular enhancement immediately after USPIO injection, some of which changed appearance 24 h later, having a ring enhancement at the outer rim. It can be concluded that USPIO enhancement of the toxoplasmic lesions may reflect blood–brain barrier impairment and/or inflammatory reactions associated with these lesions. USPIO-enhanced imaging may be used in combination with gadolinium-enhanced imaging to provide better characterization of toxoplasmic brain lesions and, potentially, improve the differential diagnosis of toxoplasmosis encephalitis.     

低频振荡电位的能量和相位稳定性与偶极子电流活动相关性的仿真

能量和相位是分析脑节律的重要物理量, 虽有许多研究, 但其与脑组织电特性和脑节律源的关系尚不完全清楚, 弄清这一问题有助于脑电测量及脑功能和疾病的分析. 为此, 借鉴脑电正问题研究方法, 大脑可看作均匀球, 脑组织电特性用导体各向同性和各向异性电导率来表示, 脑节律源用准静态偶极子电流来模拟, 其活动表达为较低频率的正弦振荡, 在改变该活动的振幅和相位时程时, 用球表面剖分网格的振荡电位仿真脑节律, 提取节律的能量和相位, 计算源和节律的窄带相位稳定性. 结果表明: 仿真节律的能量随电导率增大而减小, 受网格位置、电导率各向异性、偶极子电流幅值和偏心位置影响较大; 但仿真节律的相位稳定性只与自身的相位时程有关. 说明能量与相位稳定性电学意义无交集, 同时用来分析脑节律可提供更多神经信息; 能量的电学意义更复杂, 取决于包括测量条件在内的多种因素; 相位稳定性的优势在于它仅与脑节律相位时程直接相关, 可预测的是脑的非线性导致的相位时程越离散, 则相位稳定性越差.     

A study of tetraphenylborate transport through rat brain lipids impregnated filter-membranes

Summary The electrical properties of rat brain lipids impregnated filtermembranes exposed to the lipophilic ion tetraphenylborate (TPhB⁻) have been studied, using electrical relaxation techniques. The state of TPhB⁻ transport system depends on the applied voltage. It was also found that the initial membrane conductance depends on the applied voltage and changes with the concentration of TPhB⁻. Our results are presented in comparison with the electrical properties of BLM exposed to TPhB⁻. To speed up publication, the authors of this paper have agreed to not receive the proofs for correction.     

MR imaging findings in mild traumatic brain injury with persistent neurological impairment

Traumatic brain injury (TBI) is a widespread cause of neurologic disability, with > 70% of cases being mild in severity. Magnetic resonance imaging provides objective biomarkers in the diagnosis of brain injury by detecting brain lesions resulting from trauma. This paper reports on the detection rates of presumed trauma-related pathology using fluid-attenuated inversion recovery (FLAIR) and susceptibility-weighted imaging (SWI) in TBI patients with chronic, persistent symptoms. Methods: 180 subjects with persistent neurobehavioral symptoms following head trauma referred by personal injury attorneys and 94 asymptomatic, age-matched volunteers were included in the study. 83% of TBI subjects were classified as mild. Results: TBI subjects had a significantly greater number of lesions detected by FLAIR than controls (42% vs. 22%) and more lesions detected by SWI than controls (28% vs. 3%). To reduce the confounding effects of aging, we examined mild TBI subjects < 45 years of age, which reduced the rate of lesions detected by FLAIR (26% vs. 2%) and SWI (15% vs. 0%). This younger group, which contained few age-related lesions, also demonstrated that subcortical lesions on FLAIR are more specific for TBI than deeper lesions. Conclusions: While the presence of litigation in mild TBI cases with incomplete recovery has been associated with greater expression of symptomatology and, by extension, poorer outcomes, this study shows that mild TBI patients in litigation with chronic, persistent symptoms may have associated brain injury underlying their symptoms detectable by MRI biomarkers.     

Computational modeling of chemotactic signaling and aggregation of microglia around implantation site during deep brain stimulation

It is well established that prolonged electrical stimulation of brain tissue causes massive release of ATP in the extracellular space. The released ATP and the products of its hydrolysis, such as ADP and adenosine, become the main elements mediating chemotactic sensitivity and motility of microglial cells via subsequent activation of P2Y_2,12 as well as A3A and A2A adenosine receptors. The size of the sheath around the electrode formed by the microglial cells is an important criterion for the optimization of the parameters of electrical current delivered to brain tissue. Here, we study a purinergic signaling pathway underlying the chemotactic motion of microglia towards the implanted electrode during deep brain stimulation. We present a computational model describing formation of a stable aggregate around the implantation site due to the joint chemo-attractive action of ATP and ADP together with a mixed influence of extracellular adenosine. The model was built in accordance with the classical Keller-Segel approach and includes an equation for the cells’ density as well as equations describing the hydrolysis of extracellular ATP via successive reaction steps ATP →ADP →AMP →adenosine. The results of our modeling allowed us to reveal the dependence of the width of the encapsulating layer around the electrode on the amount of ATP released due to permanent electrical stimulation. The dependences of the aggregates’ size on the parameter governing the nonlinearity of interaction between extracellular adenosine and adenosine receptors are also analyzed.     

Age at developmental cortical injury differentially Alters corpus callosum volume in the rat

Background  

Freezing lesions to developing rat cortex induced between postnatal day (P) one and three (P1 – 3) lead to malformations similar to human microgyria, and further correspond to reductions in brain weight and cortical volume. In contrast, comparable lesions on P5 do not produce microgyric malformations, nor the changes in brain weight seen with microgyria. However, injury occurring at all three ages does lead to rapid auditory processing deficits as measured in the juvenile period. Interestingly, these deficits persist into adulthood only in the P1 lesion case [1]. Given prior evidence that early focal cortical lesions induce abnormalities in cortical morphology and connectivity [1–4], we hypothesized that the differential behavioral effects of focal cortical lesions on P1, P3 or P5 may be associated with underlying neuroanatomical changes that are sensitive to timing of injury. Clinical studies indicate that humans with perinatal brain injury often show regional reductions in corpus callosum size and abnormal symmetry, which frequently correspond to learning impairments [5–7]. Therefore, in the current study the brains of P1, 3 or 5 lesion rats, previously evaluated for brain weight, and cortical volume changes and auditory processing impairments (P21-90), were further analyzed for changes in corpus callosum volume.     

基于改进功率谱熵的抑郁症脑电信号活跃性研究

采用非线性动力学方法研究脑精神疾病是近年来国内外学者研究的热点和趋势.针对脑精神疾病的研究和诊断中缺少客观有效的量化参数和量化指标的状况,提出了一种根据对时间序列功率谱划分而定义的谱熵,然后用其计算和分析脑电信号谱熵的方法.通过数据仿真试验证明该谱熵和信号活跃性之间存在正相关关系.基于这种相关性,应用该方法对抑郁症患者和正常对照组的脑电信号功率谱熵进行了数值计算,然后进行了分析对比和统计检验.实验结果表明:抑郁症患者脑电信号的功率谱熵在部分脑区显著弱于正常健康人.证明该谱熵能够表征大脑电生理活动状况,提供反映其活动性强弱的信息,可以作为度量大脑电生理活动性的一个参数.这对于能否将该功率谱熵作为诊断脑精神疾病的物理参数具有积极意义.     

Automated Detection and Characterization of Multiple Sclerosis Lesions in Brain MR Images

In the present study an automatic algorithm for detection and contouring of multiple sclerosis (MS) lesions in brain magnetic resonance (MR) images is introduced. This algorithm automatically detects MS lesions in axial proton density, T₂-weighted, gadolinium enhanced, and fast fluid attenuated inversion recovery (FLAIR) brain MR images. Automated detection consists of three main stages: (1) detection and contouring of all hyperintense signal regions within the image; (2) partial elimination of false positive segments (defined herein as artifacts) by size, shape index, and anatomical location; (3) the use of an artificial neural paradigm (Back-Propagation) for final removal of artifacts by differentiating them from true MS lesions. The algorithm was applied to 45 images acquired from 14 MS patients. The algorithm’s sensitivity was 0.87 and the specificity 0.96. In 34 images, 100% of the lesions were detected. The algorithm potentially may serve as a useful preprocessing tool for quantitative MS monitoring via magnetic resonance imaging.     

An approach for computer-aided detection of brain metastases in post-Gd T1-W MRI

Purpose

To develop an approach for computer-aided detection (CAD) of small brain metastases in post-Gd T1-weighted magnetic resonance imaging (MRI).

Method

A set of unevenly spaced 3D spherical shell templates was optimized to localize brain metastatic lesions by cross-correlation analysis with MRI. Theoretical and simulation analyses of effects of lesion size and shape heterogeneity were performed to optimize the number and size of the templates and the cross-correlation thresholds. Also, effects of image factors of noise and intensity variation on the performance of the CAD system were investigated. A nodule enhancement strategy to improve sensitivity of the system and a set of criteria based upon the size, shape and brightness of lesions were used to reduce false positives. An optimal set of parameters from the FROC curves was selected from a training dataset, and then the system was evaluated on a testing dataset including 186 lesions from 2753 MRI slices. Reading results from two radiologists are also included.

Results

Overall, a 93.5% sensitivity with 0.024 of intra-cranial false positive rate (IC-FPR) was achieved in the testing dataset. Our investigation indicated that nodule enhancement was very effective in improving both sensitivity and specificity. The size and shape criteria reduced the IC-FPR from 0.075 to 0.021, and the brightness criterion decreases the extra-cranial FPR from 0.477 to 0.083 in the training dataset. Readings from the two radiologists had sensitivities of 60% and 67% in the training dataset and 70% and 80% in the testing dataset for the metastatic lesions <5 mm in diameter.

Conclusion

Our proposed CAD system has high sensitivity and fairly low FPR for detection of the small brain metastatic lesions in MRI compared to the previous work and readings of neuroradiologists. The potential of this method for assisting clinical decision- making warrants further evaluation and improvements.     

In vivo NMR imaging and T1 measurements of water protons in the human brain

Nuclear magnetic resonance (NMR) proton density images of the human brain have been made by the FONAR method. Spin-lattice relaxation times, T₁, of water hydrogen protons have been determined at random positions within frontal and temporal regions of the human brain. The primary purpose of this ongoing research is to accumulate a large data base of normal T₁ values for water protons in normal human brain tissue. Our experience to data includes 31 measurements on 18 volunteer subjects, and the mean value ± standard deviation is 215 ± 42 msec. In addition, two metastatic lesions of the brain were studied and found to have T₁ values longer than those for normal brain tissue.     

Self-organized criticality model for brain plasticity

Networks of living neurons exhibit an avalanche mode of activity, experimentally found in organotypic cultures. Here we present a model that is based on self-organized criticality and takes into account brain plasticity, which is able to reproduce the spectrum of electroencephalograms (EEG). The model consists of an electrical network with threshold firing and activity-dependent synapse strengths. The system exhibits an avalanche activity in a power-law distribution. The analysis of the power spectra of the electrical signal reproduces very robustly the power-law behavior with the exponent 0.8, experimentally measured in EEG spectra. The same value of the exponent is found on small-world lattices and for leaky neurons, indicating that universality holds for a wide class of brain models.     

Nonlinear denoising of transient signals with application to event-related potentials

We present a new wavelet-based method for the denoising of event-related potentials (ERPs), employing techniques recently developed for the paradigm of deterministic chaotic systems. The denoising scheme has been constructed to be appropriate for short and transient time sequences using circular state space embedding. Its effectiveness was successfully tested on simulated signals as well as on ERPs recorded from within a human brain. The method enables the study of individual ERPs against strong ongoing brain electrical activity.     

Fast flair imaging of the brain using the fast spin-echo and gradient spin-echo technique

The purpose of this study was to compare the gradient spin-echo (GRASE) to the fast spin-echo (FSE) implementation of fast fluid-attenuated inversion recovery (FLAIR) sequences for brain imaging. Thirty patients with high signal intensity lesions on T₂-weighted images were examined on a 1.5 T MR system. Scan time-minimized thin-section FLAIR-FSE and FLAIR-GRASE sequences were obtained and compared side by side. Image assessment criteria were lesion conspicuity, contrast between different types of normal tissue, image quality, and artifacts. In addition, contrast ratios and contrast-to-noise ratios were determined. Compared to FSE, the GRASE technique allowed a 17% reduction in scan time but conspicuity of small lesions in particular was significantly lower on FLAIR-GRASE images because of higher image noise and increased artifacts. Gray-white differentiation was slightly worse on FLAIR-GRASE. Physiological ferritin deposition appeared slightly darker on FLAIR-GRASE images and susceptibility artifacts were stronger. Fatty tissue was less bright with FLAIR-GRASE. With current standard hardware equipment, the GRASE technique is not an adequate alternative to FSE for the implementation of fast FLAIR sequences in routine clinical MR brain imaging.     

Automatic localization of EEG electrode markers within 3D MR data

The electrical activity of the brain can be monitored using ElectroEncephaloGraphy (EEG). From the positions of the EEG electrodes, it is possible to localize focal brain activity. Thereby, the accuracy of the localization strongly depends on the accuracy with which the positions of the electrodes can be determined. In this work, we present an automatic, simple, and accurate scheme that detects EEG electrode markers from 3D MR data of the human head.     

A case of polymicrogyria in macaque monkey: impact on anatomy and function of the motor system

Background  

Polymicrogyria is a malformation of the cerebral cortex often resulting in epilepsy or mental retardation. It remains unclear whether this pathology affects the structure and function of the corticospinal (CS) system. The anatomy and histology of the brain of one macaque monkey exhibiting a spontaneous polymicrogyria (PMG monkey) were examined and compared to the brain of normal monkeys. The CS tract was labelled by injecting a neuronal tracer (BDA) unilaterally in a region where low intensity electrical microstimulation elicited contralateral hand movements (presumably the primary motor cortex in the PMG monkey).     

Mechanism of taste; electrochemistry,receptors and signal transduction

This report describes a novel mechanistic approach based on electrochemistry, receptors and signal transduction. Part A presents limited correlation between dipole moments and associated electrostatic fields (EFs), and taste. For Part B, binding of the tastant to the receptor results in interaction of the ligand EF with those of the protein receptor. Part C addresses passage of the message by the altered EF to the gustatory neurons, involving electrical effects and signal transduction. Insight is gained from external electrical stimulus. Part D represents the final step in which the electrical signal is converted to perceived taste in the brain.     

A map describing EEG activity of human brain

A model of electrical activity of human brain considered as a complex dynamical system is given based on the EEG time series. The model fits the data remarkably well. The predictive ability of the model is limited to a few time steps as expected for a chaotic time series.     

Correlation between enhancing lesion number and volume on standard and triple dose gadolinium-enhanced brain MRI scans from patients with multiple sclerosis.

We investigated the correlations between numbers and volumes of multiple sclerosis (MS) lesions enhancing on standard dose (SD) and triple dose (TD) gadolinium (Gd)-enhanced brain magnetic resonance imaging (MRI) scans, to clarify whether the measurement of enhancing lesion volumes or the use of TD MRI give additional information which can not be obtained by counting enhancing lesions on SD scans. SD and TD Gd-enhanced brain MRI scans were obtained every month for three months from 40 MS patients. The numbers of total and new enhancing lesions were counted, and the total volumes of enhancing lesions were measured from each of the four scans obtained with the two techniques. Univariate correlations between enhancing lesion numbers and volumes were assessed. The numbers of total and new enhancing lesions seen either on SD or TD scans were significantly correlated (r = 0.91 and 0.93, respectively). The numbers and volumes of total enhancing lesions were significantly correlated on both SD (r = 0.90), and TD (r = 0.89) scans. Moderate correlations were found between the total number of enhancing lesions on SD scans and the average difference between TD and SD scans for total enhancing lesion number (r = 0.66), and between the number of new enhancing lesions on SD scans and the average difference between TD and SD scans for new enhancing lesion number (r = 0.50). Our findings indicate that, both on SD and TD MRI, the counts and the volumes of total and new enhancing lesions are highly correlated, and that lesion counting may suffice to monitor MS activity. On the contrary, this study confirms the usefulness of TD MRI for a more complete assessment of the acute changes occurring in MS patients.     

Diffusion Tensor Magnetic Resonance Imaging in Ring-Enhancing Cerebral Lesions

The objective of this study is to determine differential diagnostic value of diffusion tensor imaging (DTI) in high-grade brain astrocytomas, brain solitary metastases and brain abscesses. 53 patients with cerebral solitary lesions which showed ring enhancement on contrast-enhanced T ₁-weighted images were enrolled in this study. Brain tissues were examined pathologically from 49 patients to confirm the cerebral occupational diseases. Four patients have been diagnosed with primary cancer plus brain solitary metastasis. DTI measurements were obtained from regions of interest placed on central cavity, white matter of the immediate peritumoral region (IPR) and cerebral white matter of the normal side. The cavity of high-grade astrocytoma and brain metastases displayed hypointense signals; most of the brain abscess cavities displayed high signal intensity except for one case with uneven signal intensity. Mean diffusivity (MD) and fractional anisotropy (FA) values could be used for differentiation between tumor and abscess in brain. The brain abscess cavities showed restricted diffusion and anisotropy [MD = (0.604 ± 0.13) × 10⁻³ mm²/s, FA = 0.185 ± 0.03], whereas the central portion of high-grade astrocytoma [MD = (2.76 ± 0.26) × 10⁻³ mm²/s, FA = 0.069 ± 0.02] and solitary brain metastases [MD = (2.82 ± 0.29) × 10⁻³ mm²/s, FA = 0.064 ± 0.02] showed unrestricted diffusion and isotropy. Brain abscess could be differentiated by MD and FA values in their cavities from brain tumors (P < 0.01). The IPRs were all depicted as hyperintense or isointense signals on diffusion-weighted imaging. The difference between FA values in the IPR of high-grade brain astrocytomas and other groups was statistically significant (P < 0.01). In conclusion, our results suggested the potential role of the cavity MD and FA values in the differential diagnoses of brain tumors and brain abscesses; meanwhile, high-grade astrocytomas could be distinguished from solitary metastases and abscesses by evaluating their corresponding FA values in the IPR on brain magnetic resonance imaging (MRI). Combined with conventional MRI, DTI may help radiologists to facilitate the differential diagnosis of ring-enhancing cerebral lesions in clinical practice.