Entire Brain Area Research Articles

NIMG-04. PRE-RADIATION PROGRESSION PREDICTION IN GLIOBLASTOMA PATIENTS

Abstract Pre-Radiation Progression (PRP) has been identified as an increase ( > 25%) in the size of the residual brain tumor or interval development of a new tumor after surgical resection but prior to radiation therapy. Glioblastoma (GB) patients with PRP have worse survival outcome compared to patients without PRP (non-PRP).The standardized approach to identify PRP in GB patients is to manually compare early post-operative MRI to radiation planning MRI. In this study, we investigate the efficacy of traditional radiomics and sophisticated multi-resolution fractal texture features to differentiate PRP from non-PRP. Radiation-planning T1C magnetic resonance imaging (MRI) of 13 PRP and 13 non-PRP patients is analyzed to develop the classification method. For each patient, around 600 conventional radiomics and fractal texture features are obtained from tumor tissue and entire brain areas. We propose a two-step feature selection process followed by ensemble classification. In the first step of feature selection, we apply a beta-mixture based graphical model to identify correlations between the extracted features. The features are the nodes of the graph and the edges of the graph denote the correlations among the features and adjacency to PRP node. After the first step feature selection, the 21 selected features are used in the second step feature selection based on accuracy, similarity, and stability of each feature to yield the final 12 features. Lastly, we utilize the final 12 selected features for ensemble classification of PRP from non-PRP. With leave-one-out cross validation, the predictive model has an area under curve (AUC) of 0.79 and accuracy of 80% which indicates the discriminatory function of imaging features to differentiate PRP patients from non-PRP. The experimental results show the diagnostic ability of radiation planning imaging features to predict PRP from non-PRP.

A method for ultrafast tissue clearing that preserves fluorescence for multimodal and longitudinal brain imaging

BackgroundTissue-clearing techniques have recently been developed to make tissues transparent for three-dimensional (3D) imaging at different scales, including single-cell resolution. However, current tissue-clearing workflows have several disadvantages, including complex protocols, time-consuming application, and fluorescence quenching. Additionally, they can be used mainly for clearing larger-volume samples, preventing wide and easy applicability in conventional experimental approaches. In this study, we aimed to develop a versatile, fast, and convenient method for clearing thin and semi-thick samples, which can be used for three-dimensional imaging of experimental or even clinical samples.ResultsWe developed an alkaline solution (AKS) containing a combination of 2,2′-thiodiethanol (TDE), DMSO, D-sorbitol, and Tris for tissue clearing, as the alkaline environment is suitable for maintaining the fluorescence of most commonly used fluorescence protein GFP and its variants, and tested its clearing effect on samples from mice and human brains. We assessed the clearing speed, the preservation of fluorescence protein and dyes, and the imaging depth and quality. The results showed that AKS treatment rapidly cleared 300-μm-thick brain slices and 1-mm-thick slices from different organs within 5 min and 1 h, respectively. Moreover, AKS was compatible with a variety of fluorescence proteins and dyes. Most importantly, AKS enhanced the fluorescence of YFP, in contrast to the majority of existing tissue-clearing methods which reduce the fluorescence intensity of fluorescent proteins. Using AKS, we performed long-time high-resolution imaging of weak fluorescent protein-labelled tissues, long-distance fibre tracking, larger-scale 3D imaging and cell counting of the entire brain area, neural circuit tracing, 3D neuromorphic reconstruction, and 3D histopathology imaging.ConclusionsAKS can be used for simple and rapid clearing of samples from mice and human brains and is widely compatible with a variety of fluorescent dyes. Therefore, AKS has great potential to be used as a broad tissue-clearing reagent for biological optical imaging, especially for time-sensitive experiments.

Visualizing synaptic plasticity in vivo by large-scale imaging of endogenous AMPA receptors.

Elucidating how synaptic molecules such as AMPA receptors mediate neuronal communication and tracking their dynamic expression during behavior is crucial to understand cognition and disease, but current technological barriers preclude large-scale exploration of molecular dynamics in vivo. We have developed a suite of innovative methodologies that break through these barriers: a new knockin mouse line with fluorescently tagged endogenous AMPA receptors, two-photon imaging of hundreds of thousands of labeled synapses in behaving mice, and computer vision-based automatic synapse detection. Using these tools, we can longitudinally track how the strength of populations of synapses changes during behavior. We used this approach to generate an unprecedentedly detailed spatiotemporal map of synapses undergoing changes in strength following sensory experience. More generally, these tools can be used as an optical probe capable of measuring functional synapse strength across entire brain areas during any behavioral paradigm, describing complex system-wide changes with molecular precision.

Increased Temporal Lobe Beta Activity in Boys With Attention-Deficit Hyperactivity Disorder by LORETA Analysis.

Aim: Attention-deficit hyperactivity disorder (ADHD) is a common childhood neuropsychiatric disorder that affects 6.1 million US children. The mechanism of ADHD is currently unclear. Differences in ADHD presentations between boys and girls are well-established. In the present study, we used quantitative electroencephalography (EEG) to investigate the brain area and EEG bands of boys with ADHD.Methods: This study enrolled 40 boys with ADHD and 40 age-matched controls without ADHD. Low-resolution electromagnetic tomography (LORETA) and instantaneous frequency were used to analyze EEG data to reveal the mechanisms underlying ADHD in boys.Results: We found that the instantaneous frequencies in the T3 and T4 EEG channels in boys with ADHD were significantly higher than those in the controls. The beta band showed significant difference in current density between the ADHD and control groups. In the entire brain area, the bilateral inferior and middle temporal gyrus exhibited the most significant difference between the ADHD and control groups in the EEG beta band. Connectivity analysis revealed an increase in connectivity between the left middle frontal gyrus and fusiform gyrus of the temporal lobe in boys with ADHD.Conclusions: LORETA is a promising tool for analyzing EEG signals and can be used to investigate the mechanism of ADHD. Our results reveal that the inferior temporal gyrus, middle temporal gyrus, and fusiform gyrus of the temporal lobe are potentially involved in the pathogenesis of ADHD in boys. In comparison with other imaging methods, such as magnetic resonance imaging, EEG is easy to perform, fast, and low cost. Our study presents a new approach for investigating the pathogenesis of ADHD in boys.

Neurobiological influence of comorbid conditions in young patients diagnosed with gaming disorder: A whole-brain functional connectivity study based on a data driven method.

Gaming disorder, which is characterized by multiple cognitive and behavioral symptoms, often has comorbid psychiatric conditions such as depression and attention-deficit hyperactivity disorder. Neurobiological effects of the comorbid disorders so far reported are not converging, exhibiting positive and negative alterations of the connectivity in brain networks. In this study, we conducted resting-state functional magnetic-resonance imaging and whole brain functional connectivity analyses for young participants consisting of 40 patients diagnosed with the gaming disorder, with and without comorbid conditions, and 29 healthy controls. Compared to healthy controls, the gaming disorder-alone patients had partially diminished connectivities in the reward system and executive control network, within which there existed central nodes that served as a hub of diminished connections. In the gaming disorder patients who had comorbidity of autism spectrum disorder, the diminished connections were enlarged, with alteration of the hub nodes, to the entire brain areas involved in the reward system including cortical, subcortical and limbic areas that are crucial for reward processing, and to the whole cortical areas composing the executive control network. These observations suggest that the neurodevelopmental condition coexisting with the gaming disorder induced substantial impairment of the neural organizations associated with executive/cognitive and emotional functions, which are plausibly causal to the behavioral addiction, by rearranging and diminishing functional connectivities in the network.

Delay Maturation in Occipital Lobe in Girls With Inattention Subtype of Attention-Deficit Hyperactivity Disorder.

Attention-deficit hyperactivity disorder (ADHD) is a common childhood neuropsychiatric disorder. Differences in the presentations of ADHD between boys and girls have been well established. Three subtypes of ADHD exist. In addition to sex difference, different mechanisms may underlie different subtypes. The present study enrolled 30 girls with the inattentive subtype of ADHD and 30 age-matched controls. Low-resolution electromagnetic tomography (LORETA) and instantaneous frequency were used to analyze electroencephalography (EEG) for investigating the brain area and EEG bands involved in girls with inattentive ADHD. We found that the instantaneous frequencies in all EEG channels in girls with ADHD were lower than those in controls. Alpha 2 was the only EEG band that showed significant difference in current density between the ADHD and control groups (P = .0014). In the entire brain area, the posterior cingulate cortex, cingulate gyrus, and precuneus demonstrated the most significant difference between the ADHD and control groups. Our results suggest that brain maturation delay in the posterior areas might result in the inattention subtype of ADHD. In addition, posterior cingulate cortex, cingulate gyrus, and precuneus may play a critical role in the pathogenesis of ADHD. Our study provides a new approach method and possible mechanism of girls with inattentive subtype ADHD.

An Automated Brain Tumour Boundary Detection using Region based Segmentation Technique along with SVM Classifier

We presents a fully automated method for an automated brain-tumour boundary detection using region based segmentation technique along with SVM Classifier of Magnetic Resonance Imaging (MRI).The procedure is based on artificial intelligence technique and classification of each super-pixel in MRI. A number of novel image features extraction approaches including intensity-based, texture based, fractal analysis and curvatures are calculated from each super-pixel within the entire brain area in MRI to ensure a robust classification. Brain tumor is the malignant types of cancer and their classification in earlier stage is biggest issue. While curable with early classification is useful, only extremely trained specialists are capable of accurately recognizing the cancer from skin MRI data. As expertise is in limited contribute, an automated systems capable of classifying cancer could save human lives, and also help to reduce unnecessary MRI, and reduce extra costs. On the way to achieve this goal, we proposed a Brain Tumour Detection and Classification System (BTDCS) that combines recent developments in machine learning with Support Vector Machine (SVM) structure, creating hybrid algorithm of threshold based segmentation with Maximally Stable External Regions (MSER) that are capable of segmenting accurate super-pixel region from MRI, as well as analyzing the detected area and surrounding tissue for malignant. Using threshold based segmentation technique, the foreground and background component is separated into two regions. To improve the segmentation results, MSER is used with the novel concept of region detection and feature extraction mechanism. The proposed system is evaluated using the largest publicly accessible standard BRATS 2015 dataset of MRI, containing benign and malignant images. When the evaluation parameters of proposed work is compared with a few other state-of-art methods, the proposed means attains the best performance of 98.2% concerning classification accuracy using only the MSER approach and SVM as classifier. The ultimate aim of this research is to devise an automated experimental approach that can segment the tumor boundary in a fast and efficient manner.

When an octopus has MS: Application of neurophysiology and immunology of octopuses for multiple sclerosis

Multiple sclerosis (MS) is an immune-mediated disease which can cause different symptoms due to the involvement of different regions of the central nervous system (CNS). Although this disease is characterized by the demyelination process, the most important feature of the disease is its degenerative nature. This nature is clinically manifested as progressive symptoms, especially in patients’ walking, which can even lead to complete debilitation. Therefore, finding a treatment to prevent the degenerative processes is one of the most important goals in MS studies. To better understand the process and the effect of drugs, scientists use animal models which mostly consisting of mouse, rat, and monkey.In evolutionary terms, octopuses belong to the invertebrates which have many substantial differences with vertebrates. One of these differences is related to the nervous system of these organisms, which is divided into central and peripheral parts. The difference lies in the fact that the main volume of this system expands in the limbs of these organisms instead of their brain. This offers a kind of freedom of action and processing strength in the octopus limbs. Also, the brain of these organisms follows a non-somatotopic model. Although the complex actions of this organism are stimulated by the brain, in contrast to the human brain, this activity is not related to a specific region of the brain; rather the entire brain area of the octopus is activated during a process. Indeed, the brain mapping or the topological perception of a particular action, such as moving the limbs, reflects itself in how that activity is distributed in the octopus brain neurons. Accordingly, various actions are known with varying degrees of activity of neurons in the brain of octopus. Another important feature of octopuses is their ability to regenerate defective tissues including the central and peripheral nervous system.These characteristics raise the question of what features can an octopus show when it is used as an organism to create experimental autoimmune encephalomyelitis (EAE). Can the immune system damage of the octopus brain cause a regeneration process? Will the autonomy of the organs reduce the severity of the symptoms?This article seeks to provide evidence to prove that use of octopuses as laboratory samples for generation of EAE may open up new approaches for researchers to better approach MS.

Development and Experimental Validation of a Dry Non-Invasive Multi-Channel Mouse Scalp EEG Sensor through Visual Evoked Potential Recordings.

In this paper, we introduce a dry non-invasive multi-channel sensor for measuring brainwaves on the scalps of mice. The research on laboratory animals provide insights to various practical applications involving human beings and other animals such as working animals, pets, and livestock. An experimental framework targeting the laboratory animals has the potential to lead to successful translational research when it closely resembles the environment of real applications. To serve scalp electroencephalography (EEG) research environments for the laboratory mice, the dry non-invasive scalp EEG sensor with sixteen electrodes is proposed to measure brainwaves over the entire brain area without any surgical procedures. We validated the proposed sensor system with visual evoked potential (VEP) experiments elicited by flash stimulations. The VEP responses obtained from experiments are compared with the existing literature, and analyzed in temporal and spatial perspectives. We further interpret the experimental results using time-frequency distribution (TFD) and distance measurements. The developed sensor guarantees stable operations for in vivo experiments in a non-invasive manner without surgical procedures, therefore exhibiting a high potential to strengthen longitudinal experimental studies and reliable translational research exploiting non-invasive paradigms.

Application of hairless mouse strain to bioluminescence imaging of Arc expression in mouse brain

BackgroundBioluminescence imaging (BLI) is a powerful technique for monitoring the temporal and spatial dynamics of gene expression in the mouse brain. However, the black fur, skin pigmentation and hair regrowth after depilation of mouse interfere with BLI during developmental and daily examination. The aim of this study was to extend the application of Arc-Luc transgenic (Tg) mice to the BLI of neuronal activity in the mouse brain by introducing the hairless (HL) gene and to examine Arc-Luc expression at various developmental stages without interference from black fur, skin pigmentation, and hair regrowth.ResultsThe Arc-Luc Tg HL mice were established by crossing the Tg C57BL/6 mouse strain with the HL mouse strain. Under physiological and pathological conditions, BLI was performed to detect the signal intensity changes at various developmental stages and at an interval of <7 days. The established Arc-Luc Tg HL mice exhibited clear and stable photon signals from the brain without interference during development. After surgical monocular deprivation during visual-critical period, large signal intensity changes in bioluminescence were observed in the mouse visual cortex. Exposure of mice to a novel object changed the photon distribution in the caudal and rostral cerebral areas. The temporal pattern of kainic-acid-induced Arc-Luc expression showed biphasic changes in signal intensity over 24 h.ConclusionsThis study showed the advantages of using the mutant HL gene in BLI of Arc expression in the mouse brain at various developmental stages. Thus, the use of the Arc-Luc Tg HL mice enabled the tracking of neuronal-activity-dependent processes over a wide range from a focal area to the entire brain area with various time windows.

Automated brain tumour detection and segmentation using superpixel-based extremely randomized trees in FLAIR MRI

PurposeWe propose a fully automated method for detection and segmentation of the abnormal tissue associated with brain tumour (tumour core and oedema) from Fluid- Attenuated Inversion Recovery (FLAIR) Magnetic Resonance Imaging (MRI).MethodsThe method is based on superpixel technique and classification of each superpixel. A number of novel image features including intensity-based, Gabor textons, fractal analysis and curvatures are calculated from each superpixel within the entire brain area in FLAIR MRI to ensure a robust classification. Extremely randomized trees (ERT) classifier is compared with support vector machine (SVM) to classify each superpixel into tumour and non-tumour.ResultsThe proposed method is evaluated on two datasets: (1) Our own clinical dataset: 19 MRI FLAIR images of patients with gliomas of grade II to IV, and (2) BRATS 2012 dataset: 30 FLAIR images with 10 low-grade and 20 high-grade gliomas. The experimental results demonstrate the high detection and segmentation performance of the proposed method using ERT classifier. For our own cohort, the average detection sensitivity, balanced error rate and the Dice overlap measure for the segmented tumour against the ground truth are 89.48 %, 6 % and 0.91, respectively, while, for the BRATS dataset, the corresponding evaluation results are 88.09 %, 6 % and 0.88, respectively.ConclusionsThis provides a close match to expert delineation across all grades of glioma, leading to a faster and more reproducible method of brain tumour detection and delineation to aid patient management.

Toward a distributed free-floating wireless implantable neural recording system.

To understand the complex correlations between neural networks across different regions in the brain and their functions at high spatiotemporal resolution, a tool is needed for obtaining long-term single unit activity (SUA) across the entire brain area. The concept and preliminary design of a distributed free-floating wireless implantable neural recording (FF-WINeR) system are presented, which can enabling SUA acquisition by dispersedly implanting tens to hundreds of untethered 1 mm3 neural recording probes, floating with the brain and operating wirelessly across the cortical surface. For powering FF-WINeR probes, a 3-coil link with an intermediate high-Q resonator provides a minimum S21 of -22.22 dB (in the body medium) and -21.23 dB (in air) at 2.8 cm coil separation, which translates to 0.76%/759 μW and 0.6%/604 μW of power transfer efficiency (PTE) / power delivered to a 9 kΩ load (PDL), in body and air, respectively. A mock-up FF-WINeR is implemented to explore microassembly method of the 1×1 mm2 micromachined silicon die with a bonding wire-wound coil and a tungsten micro-wire electrode. Circuit design methods to fit the active circuitry in only 0.96 mm2 of die area in a 130 nm standard CMOS process, and satisfy the strict power and performance requirements (in simulations) are discussed.

Degree centrality and fractional amplitude of low-frequency oscillations associated with Stroop interference

Stroop paradigms are commonly used as an index of attention deficits and a tool for investigating functions of the frontal lobes and other associated structures. Here we investigated the correlation between resting-state functional magnetic imaging (fMRI) measures [degree centrality (DC)/fractional amplitude of low frequency fluctuations (fALFFs)] and Stroop interference. We examined this relationship in the brains of 958 healthy young adults. DC reflects the number of instantaneous functional connections between a region and the rest of the brain within the entire connectivity matrix of the brain (connectome), and thus how much of the node influences the entire brain areas, while fALFF is an indicator of the intensity of regional brain spontaneous activity. Reduced Stroop interference was associated with larger DC in the left lateral prefrontal cortex, left IFJ, and left inferior parietal lobule as well as larger fALFF in the areas of the dorsal attention network and the precuneus. These findings suggest that Stroop performance is reflected in resting state functional properties of these areas and the network. In addition, default brain activity of the dorsal attention network and precuneus as well as higher cognitive processes represented there, and default stronger global influence of the areas critical in executive functioning underlie better Stroop performance.

Role of NMDA receptors in adult neurogenesis: an ontogenetic (re)view on activity-dependent development.

It is now widely accepted that neurogenesis continues throughout life. Accumulating evidence suggests that neurotransmitters are essential signaling molecules that control the different steps of neurogenesis. Nevertheless, we are only beginning to understand the precise role of neurotransmitter receptors andin particular excitatory glutamatergic transmission in the differentiation of adult-born neurons. Recent technical advances allow single-cell gene deletion to study cell-autonomous effects during the maturation of adult-born neurons. Single-cell gene deletion overcomes some of the difficulties in interpreting global gene deletion effects on entire brain areas or systemic pharmacological approaches that might result in compensatory circuit effects. The aim of this review is to summarize recent advances in the understanding of the role of NMDA receptors (NMDARs) during the differentiation of adult-born neurons and put them in perspective with previous findings on cortical development.

Voxel-based Investigations of Phase Mask Effects on Susceptibility Weighted Images

To investigate effects of phase mask on susceptibility-weighted images (SWI) using voxel-based analyses in normal elderly subjects. A three-dimensional (3D) gradient echo sequence ran to obtain SWIs in 20 healthy elderly subjects. SWIs with two (SWI2) and four (SWI4) phase multiplications were achieved with positive (PSWI) and negative (NSWI) phase masks to investigate phase mask effects. The voxel-based comparisons were performed using paired t-tests between PSWI and NSWI and between SWI2 and SWI4. Differences of signal intensities between magnitude images and SWI4 were larger than those between magnitude images and SWI2s. Differences of signal intensities between magnitude images and PSWIs were larger than those between magnitude images and NSWIs. Moreover, the signal intensities from NSWI2s and NSWI4s were greater than those from PSWI2s and PSWI4s, respectively. More differences of signal intensities between NSWI4 and PSWI4s were found than those between NSWI2s and PSWI2s in the whole brain images. The voxel-based analyses of SWI could be beneficial to investigate susceptibility differences on the entire brain areas. The phase masking method could be chosen to enhance brain tissue contrast rather than to enhance venous blood vessels. Therefore, it is recommended to apply voxel-based analyses of SWI to investigate clinical applications.

Prey capture in zebrafish larvae serves as a model to study cognitive functions

Prey capture in zebrafish larvae is an innate behavior which can be observed as early as 4~days postfertilization, the day when they start to swim. This simple behavior apparently involves several neural processes including visual perception, recognition, decision-making, and motor control, and, therefore, serves as a good model system to study cognitive functions underlying natural behaviors in vertebrates. Recent progresses in imaging techniques provided us with a unique opportunity to image neuronal activity in the brain of an intact fish in real-time while the fish perceives a natural prey, paramecium. By expanding this approach, it would be possible to image entire brain areas at a single-cell resolution in real-time during prey capture, and identify neuronal circuits important for cognitive functions. Further, activation or inhibition of those neuronal circuits with recently developed optogenetic tools or neurotoxins should shed light on their roles. Thus, we will be able to explore the prey capture in zebrafish larvae more thoroughly at cellular levels, which should establish a basis of understanding of the cognitive function in vertebrates.

Multiple circular-circular correlation coefficients for the quantification of phase synchronization processes in the brain

Phase synchronization is discussed as a potential mechanism for large-scale integration in the brain. Therefore, the quantification of such synchrony is a crucial topic in brain science research. Furthermore, these cerebral integration processes are likely to involve entire brain areas; therefore, the analysis of multiple couplings is of particular interest. Because phase values are circular variables, it is possible to use circular statistical methods for their examination. In particular, circular-circular correlation coefficients form a suitable measurement to estimate the extent of phase synchronization between different signals. As a multiple circular-circular correlation concept is still pending, two new multiple circular-circular correlation coefficients are presented in this article that can be used to quantify phase couplings between one dependent and an arbitrary number of predictor signals.

Metabolic connectivity by interregional correlation analysis using statistical parametric mapping (SPM) and FDG brain PET; methodological development and patterns of metabolic connectivity in adults

Regionally connected areas of the resting brain can be detected by fluorodeoxyglucose-positron emission tomography (FDG-PET). Voxel-wise metabolic connectivity was examined, and normative data were established by performing interregional correlation analysis on statistical parametric mapping of FDG-PET data. Characteristics of seed volumes of interest (VOIs) as functional brain units were represented by their locations, sizes, and the independent methods of their determination. Seed brain areas were identified as population-based gyral VOIs (n = 70) or as population-based cytoarchitectonic Brodmann areas (BA; n = 28). FDG uptakes in these areas were used as independent variables in a general linear model to search for voxels correlated with average seed VOI counts. Positive correlations were searched in entire brain areas. In normal adults, one third of gyral VOIs yielded correlations that were confined to themselves, but in the others, correlated voxels extended to adjacent areas and/or contralateral homologous regions. In tens of these latter areas with extensive connectivity, correlated voxels were found across midline, and asymmetry was observed in the patterns of connectivity of left and right homologous seed VOIs. Most of the available BAs yielded correlations reaching contralateral homologous regions and/or neighboring areas. Extents of metabolic connectivity were not found to be related to seed VOI size or to the methods used to define seed VOIs. These findings indicate that patterns of metabolic connectivity of functional brain units depend on their regional locations. We propose that interregional correlation analysis of FDG-PET data offers a means of examining voxel-wise regional metabolic connectivity of the resting human brain.

An objective procedure for ischemic area evaluation of the stroke intraluminal thread model in the mouse and rat

Computer-assisted procedures are used to measure infarct areas in animal stroke models, but this approach usually follows the less objective manual tracing of the boundaries of the infarct. Building on previously reported methodology using scanned images of triphenyltetrazolium chloride (TTC)-stained rat brains in the intraluminal thread model, we developed an objective method to assess ischemic damage in both the mouse and rat brains. The unique addition to our approach is the use of sham-treated animals, which thereby permits the removal of normal brain white matter from the ipsilateral injured brain. All brain sections per animal were scanned simultaneously using a Microtek Scanmaker 4 flatbed scanner. Color segmentation on full color images of 2 mm coronal brain sections was performed. Using Image Pro Plus (4.0) and color segmentation, ischemic and normal white matter areas were measured in the green channel and the entire brain area in the red channel. The percent of unstained tissue was calculated for sham-treated animals and for those with cerebral ischemia. By subtracting the average unstained area of the sham-treated group from the average unstained area from the ischemic group, the ischemic area was calculated. This methodology was validated using mouse and rat permanent and transient, focal ischemia models and MK-801 in the permanent ischemia models. MK-801, dosed at 3 mg/kg i.p. prior to the injury, reduced the injury by 75% in the mouse and 44% in the rat permanent occlusion models. The benefits of this methodology include: objectivity of the analysis of the ischemic injury, use of readily available software so that costs can be contained and removal of normal subcortical white matter from the calculation. This method should allow more consistent evaluation of changes in the infarct size, therefore, resulting in reduced variability and higher productivity.

Quantitative assessment of cerebral hemodynamics using CT: stability, accuracy, and precision studies in dogs.

The limited clinical availability of currently used methods to measure regional cerebral blood volume (CBV) and cerebral blood flow (CBF) represents an important restriction. We undertook this study to evaluate a new dynamic CT method to measure CBV and CBF in normal and ischemic tissue. A total of 21 dynamic CT studies were performed in seven male beagles. The contrast enhancement curves of the carotid arteries and of various brain regions were deconvolved to obtain CBV and CBF. The stability of the deconvolution method employed was assessed by comparing three data sets obtained by analyses of one, two, and four regions of interest (ROIs), all covering the entire brain area. The accuracy of CT-derived CBF was analyzed for normal (n = 5 studies) and ischemic (n = 7 studies) brain tissue using fluorescent microspheres. Repetitive CT studies were performed to evaluate the precision of the CT measurements. The stability of the deconvolution method was high with variabilities of 2.3% (CBV), 5.9% (CBF), and 8.9% (mean transit time), respectively. The correlation between the CT and the microsphere measurements was good for both normal and ischemia studies (r > 0.78, slope > 0.9). The variability of the CT CBF (30.6%) was higher than that of the CT CBV (12.3%) measurements. Our novel dynamic CT method is stable with respect to the sizes of ROIs used, allowing for accurate measurements of CBV and CBF in both normal and ischemic tissue. Further studies are necessary to evaluate the variability of this method under controlled physiologic conditions.