High-resolution digital brain atlases: a Hubble telescope for the brain.

PubMed

Jones, Edward G; Stone, James M; Karten, Harvey J

2011-05-01

We describe implementation of a method for digitizing at microscopic resolution brain tissue sections containing normal and experimental data and for making the content readily accessible online. Web-accessible brain atlases and virtual microscopes for online examination can be developed using existing computer and internet technologies. Resulting databases, made up of hierarchically organized, multiresolution images, enable rapid, seamless navigation through the vast image datasets generated by high-resolution scanning. Tools for visualization and annotation of virtual microscope slides enable remote and universal data sharing. Interactive visualization of a complete series of brain sections digitized at subneuronal levels of resolution offers fine grain and large-scale localization and quantification of many aspects of neural organization and structure. The method is straightforward and replicable; it can increase accessibility and facilitate sharing of neuroanatomical data. It provides an opportunity for capturing and preserving irreplaceable, archival neurohistological collections and making them available to all scientists in perpetuity, if resources could be obtained from hitherto uninterested agencies of scientific support. © 2011 New York Academy of Sciences.

Towards ultrahigh resting-state functional connectivity in the mouse brain using photoacoustic microscopy

NASA Astrophysics Data System (ADS)

Hariri, Ali; Bely, Nicholas; Chen, Chen; Nasiriavanaki, Mohammadreza

2016-03-01

The increasing use of mouse models for human brain disease studies, coupled with the fact that existing high-resolution functional imaging modalities cannot be easily applied to mice, presents an emerging need for a new functional imaging modality. Utilizing both mechanical and optical scanning in the photoacoustic microscopy, we can image spontaneous cerebral hemodynamic fluctuations and their associated functional connections in the mouse brain. The images is going to be acquired noninvasively with a fast frame rate, a large field of view, and a high spatial resolution. We developed an optical resolution photoacoustic microscopy (OR-PAM) with diode laser. Laser light was raster scanned due to XY-stage movement. Images from ultra-high OR-PAM can then be used to study brain disorders such as stroke, Alzheimer's, schizophrenia, multiple sclerosis, autism, and epilepsy.

Development of a high angular resolution diffusion imaging human brain template.

PubMed

Varentsova, Anna; Zhang, Shengwei; Arfanakis, Konstantinos

2014-05-01

Brain diffusion templates contain rich information about the microstructure of the brain, and are used as references in spatial normalization or in the development of brain atlases. The accuracy of diffusion templates constructed based on the diffusion tensor (DT) model is limited in regions with complex neuronal micro-architecture. High angular resolution diffusion imaging (HARDI) overcomes limitations of the DT model and is capable of resolving intravoxel heterogeneity. However, when HARDI is combined with multiple-shot sequences to minimize image artifacts, the scan time becomes inappropriate for human brain imaging. In this work, an artifact-free HARDI template of the human brain was developed from low angular resolution multiple-shot diffusion data. The resulting HARDI template was produced in ICBM-152 space based on Turboprop diffusion data, was shown to resolve complex neuronal micro-architecture in regions with intravoxel heterogeneity, and contained fiber orientation information consistent with known human brain anatomy. Copyright © 2014 Elsevier Inc. All rights reserved.

High-resolution anatomy of the human brain stem using 7-T MRI: improved detection of inner structures and nerves?

PubMed

Gizewski, Elke R; Maderwald, Stefan; Linn, Jennifer; Dassinger, Benjamin; Bochmann, Katja; Forsting, Michael; Ladd, Mark E

2014-03-01

The purpose of this paper is to assess the value of 7 Tesla (7 T) MRI for the depiction of brain stem and cranial nerve (CN) anatomy. Six volunteers were examined at 7 T using high-resolution SWI, MPRAGE, MP2RAGE, 3D SPACE T2, T2, and PD images to establish scanning parameters targeted at optimizing spatial resolution. Direct comparisons between 3 and 7 T were performed in two additional subjects using the finalized sequences (3 T: T2, PD, MPRAGE, SWAN; 7 T: 3D T2, MPRAGE, SWI, MP2RAGE). Artifacts and the depiction of structures were evaluated by two neuroradiologists using a standardized score sheet. Sequences could be established for high-resolution 7 T imaging even in caudal cranial areas. High in-plane resolution T2, PD, and SWI images provided depiction of inner brain stem structures such as pons fibers, raphe, reticular formation, nerve roots, and periaqueductal gray. MPRAGE and MP2RAGE provided clear depiction of the CNs. 3D T2 images improved depiction of inner brain structure in comparison to T2 images at 3 T. Although the 7-T SWI sequence provided improved contrast to some inner structures, extended areas were influenced by artifacts due to image disturbances from susceptibility differences. Seven-tesla imaging of basal brain areas is feasible and might have significant impact on detection and diagnosis in patients with specific diseases, e.g., trigeminal pain related to affection of the nerve root. Some inner brain stem structures can be depicted at 3 T, but certain sequences at 7 T, in particular 3D SPACE T2, are superior in producing anatomical in vivo images of deep brain stem structures.

Multiscale Exploration of Mouse Brain Microstructures Using the Knife-Edge Scanning Microscope Brain Atlas

PubMed Central

Chung, Ji Ryang; Sung, Chul; Mayerich, David; Kwon, Jaerock; Miller, Daniel E.; Huffman, Todd; Keyser, John; Abbott, Louise C.; Choe, Yoonsuck

2011-01-01

Connectomics is the study of the full connection matrix of the brain. Recent advances in high-throughput, high-resolution 3D microscopy methods have enabled the imaging of whole small animal brains at a sub-micrometer resolution, potentially opening the road to full-blown connectomics research. One of the first such instruments to achieve whole-brain-scale imaging at sub-micrometer resolution is the Knife-Edge Scanning Microscope (KESM). KESM whole-brain data sets now include Golgi (neuronal circuits), Nissl (soma distribution), and India ink (vascular networks). KESM data can contribute greatly to connectomics research, since they fill the gap between lower resolution, large volume imaging methods (such as diffusion MRI) and higher resolution, small volume methods (e.g., serial sectioning electron microscopy). Furthermore, KESM data are by their nature multiscale, ranging from the subcellular to the whole organ scale. Due to this, visualization alone is a huge challenge, before we even start worrying about quantitative connectivity analysis. To solve this issue, we developed a web-based neuroinformatics framework for efficient visualization and analysis of the multiscale KESM data sets. In this paper, we will first provide an overview of KESM, then discuss in detail the KESM data sets and the web-based neuroinformatics framework, which is called the KESM brain atlas (KESMBA). Finally, we will discuss the relevance of the KESMBA to connectomics research, and identify challenges and future directions. PMID:22275895

Brain Atlas Fusion from High-Thickness Diagnostic Magnetic Resonance Images by Learning-Based Super-Resolution

PubMed Central

Zhang, Jinpeng; Zhang, Lichi; Xiang, Lei; Shao, Yeqin; Wu, Guorong; Zhou, Xiaodong; Shen, Dinggang; Wang, Qian

2017-01-01

It is fundamentally important to fuse the brain atlas from magnetic resonance (MR) images for many imaging-based studies. Most existing works focus on fusing the atlases from high-quality MR images. However, for low-quality diagnostic images (i.e., with high inter-slice thickness), the problem of atlas fusion has not been addressed yet. In this paper, we intend to fuse the brain atlas from the high-thickness diagnostic MR images that are prevalent for clinical routines. The main idea of our works is to extend the conventional groupwise registration by incorporating a novel super-resolution strategy. The contribution of the proposed super-resolution framework is two-fold. First, each high-thickness subject image is reconstructed to be isotropic by the patch-based sparsity learning. Then, the reconstructed isotropic image is enhanced for better quality through the random-forest-based regression model. In this way, the images obtained by the super-resolution strategy can be fused together by applying the groupwise registration method to construct the required atlas. Our experiments have shown that the proposed framework can effectively solve the problem of atlas fusion from the low-quality brain MR images. PMID:29062159

Brain Atlas Fusion from High-Thickness Diagnostic Magnetic Resonance Images by Learning-Based Super-Resolution.

PubMed

Zhang, Jinpeng; Zhang, Lichi; Xiang, Lei; Shao, Yeqin; Wu, Guorong; Zhou, Xiaodong; Shen, Dinggang; Wang, Qian

2017-03-01

It is fundamentally important to fuse the brain atlas from magnetic resonance (MR) images for many imaging-based studies. Most existing works focus on fusing the atlases from high-quality MR images. However, for low-quality diagnostic images (i.e., with high inter-slice thickness), the problem of atlas fusion has not been addressed yet. In this paper, we intend to fuse the brain atlas from the high-thickness diagnostic MR images that are prevalent for clinical routines. The main idea of our works is to extend the conventional groupwise registration by incorporating a novel super-resolution strategy. The contribution of the proposed super-resolution framework is two-fold. First, each high-thickness subject image is reconstructed to be isotropic by the patch-based sparsity learning. Then, the reconstructed isotropic image is enhanced for better quality through the random-forest-based regression model. In this way, the images obtained by the super-resolution strategy can be fused together by applying the groupwise registration method to construct the required atlas. Our experiments have shown that the proposed framework can effectively solve the problem of atlas fusion from the low-quality brain MR images.

Linear-array based full-view high-resolution photoacoustic computed tomography of whole mouse brain functions in vivo

NASA Astrophysics Data System (ADS)

Li, Lei; Zhang, Pengfei; Wang, Lihong V.

2018-02-01

Photoacoustic computed tomography (PACT) is a non-invasive imaging technique offering high contrast, high resolution, and deep penetration in biological tissues. We report a photoacoustic computed tomography (PACT) system equipped with a high frequency linear array for anatomical and functional imaging of the mouse whole brain. The linear array was rotationally scanned in the coronal plane to achieve the full-view coverage. We investigated spontaneous neural activities in the deep brain by monitoring the hemodynamics and observed strong interhemispherical correlations between contralateral regions, both in the cortical layer and in the deep regions.

Fluorescent-Protein Stabilization and High-Resolution Imaging of Cleared, Intact Mouse Brains

PubMed Central

Schwarz, Martin K.; Scherbarth, Annemarie; Sprengel, Rolf; Engelhardt, Johann; Theer, Patrick; Giese, Guenter

2015-01-01

In order to observe and quantify long-range neuronal connections in intact mouse brain by light microscopy, it is first necessary to clear the brain, thus suppressing refractive-index variations. Here we describe a method that clears the brain and preserves the signal from proteinaceous fluorophores using a pH-adjusted non-aqueous index-matching medium. Successful clearing is enabled through the use of either 1-propanol or tert-butanol during dehydration whilst maintaining a basic pH. We show that high-resolution fluorescence imaging of entire, structurally intact juvenile and adult mouse brains is possible at subcellular resolution, even following many months in clearing solution. We also show that axonal long-range projections that are EGFP-labelled by modified Rabies virus can be imaged throughout the brain using a purpose-built light-sheet fluorescence microscope. To demonstrate the viability of the technique, we determined a detailed map of the monosynaptic projections onto a target cell population in the lateral entorhinal cortex. This example demonstrates that our method permits the quantification of whole-brain connectivity patterns at the subcellular level in the uncut brain. PMID:25993380

A High-Resolution In Vivo Atlas of the Human Brain's Serotonin System.

PubMed

Beliveau, Vincent; Ganz, Melanie; Feng, Ling; Ozenne, Brice; Højgaard, Liselotte; Fisher, Patrick M; Svarer, Claus; Greve, Douglas N; Knudsen, Gitte M

2017-01-04

The serotonin (5-hydroxytryptamine, 5-HT) system modulates many important brain functions and is critically involved in many neuropsychiatric disorders. Here, we present a high-resolution, multidimensional, in vivo atlas of four of the human brain's 5-HT receptors (5-HT 1A , 5-HT 1B , 5-HT 2A , and 5-HT 4 ) and the 5-HT transporter (5-HTT). The atlas is created from molecular and structural high-resolution neuroimaging data consisting of positron emission tomography (PET) and magnetic resonance imaging (MRI) scans acquired in a total of 210 healthy individuals. Comparison of the regional PET binding measures with postmortem human brain autoradiography outcomes showed a high correlation for the five 5-HT targets and this enabled us to transform the atlas to represent protein densities (in picomoles per milliliter). We also assessed the regional association between protein concentration and mRNA expression in the human brain by comparing the 5-HT density across the atlas with data from the Allen Human Brain atlas and identified receptor- and transporter-specific associations that show the regional relation between the two measures. Together, these data provide unparalleled insight into the serotonin system of the human brain. We present a high-resolution positron emission tomography (PET)- and magnetic resonance imaging-based human brain atlas of important serotonin receptors and the transporter. The regional PET-derived binding measures correlate strongly with the corresponding autoradiography protein levels. The strong correlation enables the transformation of the PET-derived human brain atlas into a protein density map of the serotonin (5-hydroxytryptamine, 5-HT) system. Next, we compared the regional receptor/transporter protein densities with mRNA levels and uncovered unique associations between protein expression and density at high detail. This new in vivo neuroimaging atlas of the 5-HT system not only provides insight in the human brain's regional protein synthesis, transport, and density, but also represents a valuable source of information for the neuroscience community as a comparative instrument to assess brain disorders. Copyright © 2017 the authors 0270-6474/17/370120-09$15.00/0.

Compact and mobile high resolution PET brain imager

DOEpatents

Majewski, Stanislaw [Yorktown, VA; Proffitt, James [Newport News, VA

2011-02-08

A brain imager includes a compact ring-like static PET imager mounted in a helmet-like structure. When attached to a patient's head, the helmet-like brain imager maintains the relative head-to-imager geometry fixed through the whole imaging procedure. The brain imaging helmet contains radiation sensors and minimal front-end electronics. A flexible mechanical suspension/harness system supports the weight of the helmet thereby allowing for patient to have limited movements of the head during imaging scans. The compact ring-like PET imager enables very high resolution imaging of neurological brain functions, cancer, and effects of trauma using a rather simple mobile scanner with limited space needs for use and storage.

High-contrast differentiation resolution 3D imaging of rodent brain by X-ray computed microtomography

NASA Astrophysics Data System (ADS)

Zikmund, T.; Novotná, M.; Kavková, M.; Tesařová, M.; Kaucká, M.; Szarowská, B.; Adameyko, I.; Hrubá, E.; Buchtová, M.; Dražanová, E.; Starčuk, Z.; Kaiser, J.

2018-02-01

The biomedically focused brain research is largely performed on laboratory mice considering a high homology between the human and mouse genomes. A brain has an intricate and highly complex geometrical structure that is hard to display and analyse using only 2D methods. Applying some fast and efficient methods of brain visualization in 3D will be crucial for the neurobiology in the future. A post-mortem analysis of experimental animals' brains usually involves techniques such as magnetic resonance and computed tomography. These techniques are employed to visualize abnormalities in the brains' morphology or reparation processes. The X-ray computed microtomography (micro CT) plays an important role in the 3D imaging of internal structures of a large variety of soft and hard tissues. This non-destructive technique is applied in biological studies because the lab-based CT devices enable to obtain a several-micrometer resolution. However, this technique is always used along with some visualization methods, which are based on the tissue staining and thus differentiate soft tissues in biological samples. Here, a modified chemical contrasting protocol of tissues for a micro CT usage is introduced as the best tool for ex vivo 3D imaging of a post-mortem mouse brain. This way, the micro CT provides a high spatial resolution of the brain microscopic anatomy together with a high tissue differentiation contrast enabling to identify more anatomical details in the brain. As the micro CT allows a consequent reconstruction of the brain structures into a coherent 3D model, some small morphological changes can be given into context of their mutual spatial relationships.

[A modified intracellular labelling technique for high-resolution staining of neuron in 500 microm-thickness brain slice].

PubMed

Zhao, Ming-liang; Liu, Guo-long; Sui, Jian-feng; Ruan, Huai-zhen; Xiong, Ying

2007-05-01

To develop simple but reliable intracellular labelling method for high-resolution visualization of the fine structure of single neurons in brain slice with thickness of 500 microm. Biocytin was introduced into neurons in 500 microm-thickness brain slices while blind whole cell recording. Following processed for histochemistry using the avidin-biotin-complex method, stained slices were mounted in glycerol on special glass slides. Labelled cells were digital photomicrographed every 30 microm and reconstructed with Adobe Photoshop software. After histochemistry, limited background staining was produced. The resolution was so high that fine structure, including branching, termination of individual axons and even spines of neurons could be identified in exquisite detail with optic microscope. With the help of software, the neurons of interest could be reconstructed from a stack of photomicrographs. The modified method provides an easy and reliable approach to revealing the detailed morphological properties of single neurons in 500 microm-thickness brain slice. Without requisition of special equipment, it is suited to be broadly applied.

High-resolution whole-brain diffusion MRI at 7T using radiofrequency parallel transmission.

PubMed

Wu, Xiaoping; Auerbach, Edward J; Vu, An T; Moeller, Steen; Lenglet, Christophe; Schmitter, Sebastian; Van de Moortele, Pierre-François; Yacoub, Essa; Uğurbil, Kâmil

2018-03-30

Investigating the utility of RF parallel transmission (pTx) for Human Connectome Project (HCP)-style whole-brain diffusion MRI (dMRI) data at 7 Tesla (7T). Healthy subjects were scanned in pTx and single-transmit (1Tx) modes. Multiband (MB), single-spoke pTx pulses were designed to image sagittal slices. HCP-style dMRI data (i.e., 1.05-mm resolutions, MB2, b-values = 1000/2000 s/mm 2 , 286 images and 40-min scan) and data with higher accelerations (MB3 and MB4) were acquired with pTx. pTx significantly improved flip-angle detected signal uniformity across the brain, yielding ∼19% increase in temporal SNR (tSNR) averaged over the brain relative to 1Tx. This allowed significantly enhanced estimation of multiple fiber orientations (with ∼21% decrease in dispersion) in HCP-style 7T dMRI datasets. Additionally, pTx pulses achieved substantially lower power deposition, permitting higher accelerations, enabling collection of the same data in 2/3 and 1/2 the scan time or of more data in the same scan time. pTx provides a solution to two major limitations for slice-accelerated high-resolution whole-brain dMRI at 7T; it improves flip-angle uniformity, and enables higher slice acceleration relative to current state-of-the-art. As such, pTx provides significant advantages for rapid acquisition of high-quality, high-resolution truly whole-brain dMRI data. © 2018 International Society for Magnetic Resonance in Medicine.

Frozen tissue preparation for high-resolution multiplex histological analyses of human brain specimens.

PubMed

Shao, Fangjie; Jiang, Wenhong; Gao, Qingqing; Li, Baizhou; Sun, Chongran; Wang, Qiyuan; Chen, Qin; Sun, Bing; Shen, Hong; Zhu, Keqing; Zhang, Jianmin; Liu, Chong

2017-10-01

The availability of a comprehensive tissue library is essential for elucidating the function and pathology of human brains. Considering the irreplaceable status of the formalin-fixation-paraffin-embedding (FFPE) preparation in routine pathology and the advantage of ultra-low temperature to preserve nucleic acids and proteins for multi-omics studies, these methods have become major modalities for the construction of brain tissue libraries. Nevertheless, the use of FFPE and snap-frozen samples is limited in high-resolution histological analyses because the preparation destroys tissue integrity and/or many important cellular markers. To overcome these limitations, we detailed a protocol to prepare and analyze frozen human brain samples that is particularly suitable for high-resolution multiplex immunohistological studies. As an alternative, we offered an optimized procedure to rescue snap-frozen tissues for the same purpose. Importantly, we provided a guideline to construct libraries of frozen tissue with minimal effort, cost and space. Taking advantage of this new tissue preparation modality to nicely preserve the cellular information that was otherwise damaged using conventional methods and to effectively remove tissue autofluorescence, we described the high-resolution landscape of the cellular composition in both lower-grade gliomas and glioblastoma multiforme samples. Our work showcases the great value of fixed frozen tissue in understanding the cellular mechanisms of CNS functions and abnormalities.

Simulation study of a high performance brain PET system with dodecahedral geometry.

PubMed

Tao, Weijie; Chen, Gaoyu; Weng, Fenghua; Zan, Yunlong; Zhao, Zhixiang; Peng, Qiyu; Xu, Jianfeng; Huang, Qiu

2018-05-25

In brain imaging, the spherical PET system achieves the highest sensitivity when the solid angle is concerned. However it is not practical. In this work we designed an alternative sphere-like scanner, the dodecahedral scanner, which has a high sensitivity in imaging and a high feasibility to manufacture. We simulated this system and compared the performance with a few other dedicated brain PET systems. Monte Carlo simulations were conducted to generate data of the dedicated brain PET system with the dodecahedral geometry (11 regular pentagon detectors). The data were then reconstructed using the in-house developed software with the fully three-dimensional maximum-likelihood expectation maximization (3D-MLEM) algorithm. Results show that the proposed system has a high sensitivity distribution for the whole field of view (FOV). With a depth-of-interaction (DOI) resolution around 6.67 mm, the proposed system achieves the spatial resolution of 1.98 mm. Our simulation study also shows that the proposed system improves the image contrast and reduces noise compared with a few other dedicated brain PET systems. Finally, simulations with the Hoffman phantom show the potential application of the proposed system in clinical applications. In conclusion, the proposed dodecahedral PET system is potential for widespread applications in high-sensitivity, high-resolution PET imaging, to lower the injected dose. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Whole-animal imaging with high spatio-temporal resolution

NASA Astrophysics Data System (ADS)

Chhetri, Raghav; Amat, Fernando; Wan, Yinan; Höckendorf, Burkhard; Lemon, William C.; Keller, Philipp J.

2016-03-01

We developed isotropic multiview (IsoView) light-sheet microscopy in order to image fast cellular dynamics, such as cell movements in an entire developing embryo or neuronal activity throughput an entire brain or nervous system, with high resolution in all dimensions, high imaging speeds, good physical coverage and low photo-damage. To achieve high temporal resolution and high spatial resolution at the same time, IsoView microscopy rapidly images large specimens via simultaneous light-sheet illumination and fluorescence detection along four orthogonal directions. In a post-processing step, these four views are then combined by means of high-throughput multiview deconvolution to yield images with a system resolution of ≤ 450 nm in all three dimensions. Using IsoView microscopy, we performed whole-animal functional imaging of Drosophila embryos and larvae at a spatial resolution of 1.1-2.5 μm and at a temporal resolution of 2 Hz for up to 9 hours. We also performed whole-brain functional imaging in larval zebrafish and multicolor imaging of fast cellular dynamics across entire, gastrulating Drosophila embryos with isotropic, sub-cellular resolution. Compared with conventional (spatially anisotropic) light-sheet microscopy, IsoView microscopy improves spatial resolution at least sevenfold and decreases resolution anisotropy at least threefold. Compared with existing high-resolution light-sheet techniques, such as lattice lightsheet microscopy or diSPIM, IsoView microscopy effectively doubles the penetration depth and provides subsecond temporal resolution for specimens 400-fold larger than could previously be imaged.

Use of High Resolution 3D Diffusion Tensor Imaging to Study Brain White Matter Development in Live Neonatal Rats

PubMed Central

Cai, Yu; McMurray, Matthew S.; Oguz, Ipek; Yuan, Hong; Styner, Martin A.; Lin, Weili; Johns, Josephine M.; An, Hongyu

2011-01-01

High resolution diffusion tensor imaging (DTI) can provide important information on brain development, yet it is challenging in live neonatal rats due to the small size of neonatal brain and motion-sensitive nature of DTI. Imaging in live neonatal rats has clear advantages over fixed brain scans, as longitudinal and functional studies would be feasible to understand neuro-developmental abnormalities. In this study, we developed imaging strategies that can be used to obtain high resolution 3D DTI images in live neonatal rats at postnatal day 5 (PND5) and PND14, using only 3 h of imaging acquisition time. An optimized 3D DTI pulse sequence and appropriate animal setup to minimize physiological motion artifacts are the keys to successful high resolution 3D DTI imaging. Thus, a 3D rapid acquisition relaxation enhancement DTI sequence with twin navigator echoes was implemented to accelerate imaging acquisition time and minimize motion artifacts. It has been suggested that neonatal mammals possess a unique ability to tolerate mild-to-moderate hypothermia and hypoxia without long term impact. Thus, we additionally utilized this ability to minimize motion artifacts in magnetic resonance images by carefully suppressing the respiratory rate to around 15/min for PND5 and 30/min for PND14 using mild-to-moderate hypothermia. These imaging strategies have been successfully implemented to study how the effect of cocaine exposure in dams might affect brain development in their rat pups. Image quality resulting from this in vivo DTI study was comparable to ex vivo scans. fractional anisotropy values were also similar between the live and fixed brain scans. The capability of acquiring high quality in vivo DTI imaging offers a valuable opportunity to study many neurological disorders in brain development in an authentic living environment. PMID:22013426

Fusion of PET and MRI for Hybrid Imaging

NASA Astrophysics Data System (ADS)

Cho, Zang-Hee; Son, Young-Don; Kim, Young-Bo; Yoo, Seung-Schik

Recently, the development of the fusion PET-MRI system has been actively studied to meet the increasing demand for integrated molecular and anatomical imaging. MRI can provide detailed anatomical information on the brain, such as the locations of gray and white matter, blood vessels, axonal tracts with high resolution, while PET can measure molecular and genetic information, such as glucose metabolism, neurotransmitter-neuroreceptor binding and affinity, protein-protein interactions, and gene trafficking among biological tissues. State-of-the-art MRI systems, such as the 7.0 T whole-body MRI, now can visualize super-fine structures including neuronal bundles in the pons, fine blood vessels (such as lenticulostriate arteries) without invasive contrast agents, in vivo hippocampal substructures, and substantia nigra with excellent image contrast. High-resolution PET, known as High-Resolution Research Tomograph (HRRT), is a brain-dedicated system capable of imaging minute changes of chemicals, such as neurotransmitters and -receptors, with high spatial resolution and sensitivity. The synergistic power of the two, i.e., ultra high-resolution anatomical information offered by a 7.0 T MRI system combined with the high-sensitivity molecular information offered by HRRT-PET, will significantly elevate the level of our current understanding of the human brain, one of the most delicate, complex, and mysterious biological organs. This chapter introduces MRI, PET, and PET-MRI fusion system, and its algorithms are discussed in detail.

A high-resolution probabilistic in vivo atlas of human subcortical brain nuclei

PubMed Central

Pauli, Wolfgang M.; Nili, Amanda N.; Tyszka, J. Michael

2018-01-01

Recent advances in magnetic resonance imaging methods, including data acquisition, pre-processing and analysis, have benefited research on the contributions of subcortical brain nuclei to human cognition and behavior. At the same time, these developments have led to an increasing need for a high-resolution probabilistic in vivo anatomical atlas of subcortical nuclei. In order to address this need, we constructed high spatial resolution, three-dimensional templates, using high-accuracy diffeomorphic registration of T1- and T2- weighted structural images from 168 typical adults between 22 and 35 years old. In these templates, many tissue boundaries are clearly visible, which would otherwise be impossible to delineate in data from individual studies. The resulting delineations of subcortical nuclei complement current histology-based atlases. We further created a companion library of software tools for atlas development, to offer an open and evolving resource for the creation of a crowd-sourced in vivo probabilistic anatomical atlas of the human brain. PMID:29664465

Reconfigurable visible nanophotonic switch for optogenetic applications (Conference Presentation)

NASA Astrophysics Data System (ADS)

Mohanty, Aseema; Li, Qian; Tadayon, Mohammad Amin; Bhatt, Gaurang R.; Cardenas, Jaime; Miller, Steven A.; Kepecs, Adam; Lipson, Michal

2017-02-01

High spatiotemporal resolution deep-brain optical excitation for optogenetics would enable activation of specific neural populations and in-depth study of neural circuits. Conventionally, a single fiber is used to flood light into a large area of the brain with limited resolution. The scalability of silicon photonics could enable neural excitation over large areas with single-cell resolution similar to electrical probes. However, active control of these optical circuits has yet to be demonstrated for optogenetics. Here we demonstrate the first active integrated optical switch for neural excitation at 473 nm, enabling control of multiple beams for deep-brain neural stimulation. Using a silicon nitride waveguide platform, we develop a cascaded Mach-Zehnder interferometer (MZI) network located outside the brain to direct light to 8 different grating emitters located at the tip of the neural probe. We use integrated platinum microheaters to induce a local thermo-optic phase shift in the MZI to control the switch output. We measure an ON/OFF extinction ratio of >8dB for a single switch and a switching speed of 20 microseconds. We characterize the optical output of the switch by imaging its excitation of fluorescent dye. Finally, we demonstrate in vivo single-neuron optical activation from different grating emitters using a fully packaged device inserted into a mouse brain. Directly activated neurons showed robust spike firing activities with low first-spike latency and small jitter. Active switching on a nanophotonic platform is necessary for eventually controlling highly-multiplexed reconfigurable optical circuits, enabling high-resolution optical stimulation in deep-brain regions.

Resolving anatomical and functional structure in human brain organization: identifying mesoscale organization in weighted network representations.

PubMed

Lohse, Christian; Bassett, Danielle S; Lim, Kelvin O; Carlson, Jean M

2014-10-01

Human brain anatomy and function display a combination of modular and hierarchical organization, suggesting the importance of both cohesive structures and variable resolutions in the facilitation of healthy cognitive processes. However, tools to simultaneously probe these features of brain architecture require further development. We propose and apply a set of methods to extract cohesive structures in network representations of brain connectivity using multi-resolution techniques. We employ a combination of soft thresholding, windowed thresholding, and resolution in community detection, that enable us to identify and isolate structures associated with different weights. One such mesoscale structure is bipartivity, which quantifies the extent to which the brain is divided into two partitions with high connectivity between partitions and low connectivity within partitions. A second, complementary mesoscale structure is modularity, which quantifies the extent to which the brain is divided into multiple communities with strong connectivity within each community and weak connectivity between communities. Our methods lead to multi-resolution curves of these network diagnostics over a range of spatial, geometric, and structural scales. For statistical comparison, we contrast our results with those obtained for several benchmark null models. Our work demonstrates that multi-resolution diagnostic curves capture complex organizational profiles in weighted graphs. We apply these methods to the identification of resolution-specific characteristics of healthy weighted graph architecture and altered connectivity profiles in psychiatric disease.

Two-photon high-resolution measurement of partial pressure of oxygen in cerebral vasculature and tissue.

PubMed

Sakadzić, Sava; Roussakis, Emmanuel; Yaseen, Mohammad A; Mandeville, Emiri T; Srinivasan, Vivek J; Arai, Ken; Ruvinskaya, Svetlana; Devor, Anna; Lo, Eng H; Vinogradov, Sergei A; Boas, David A

2010-09-01

Measurements of oxygen partial pressure (pO(2)) with high temporal and spatial resolution in three dimensions is crucial for understanding oxygen delivery and consumption in normal and diseased brain. Among existing pO(2) measurement methods, phosphorescence quenching is optimally suited for the task. However, previous attempts to couple phosphorescence with two-photon laser scanning microscopy have faced substantial difficulties because of extremely low two-photon absorption cross-sections of conventional phosphorescent probes. Here we report to our knowledge the first practical in vivo two-photon high-resolution pO(2) measurements in small rodents' cortical microvasculature and tissue, made possible by combining an optimized imaging system with a two-photon-enhanced phosphorescent nanoprobe. The method features a measurement depth of up to 250 microm, sub-second temporal resolution and requires low probe concentration. The properties of the probe allowed for direct high-resolution measurement of cortical extravascular (tissue) pO(2), opening many possibilities for functional metabolic brain studies.

High Resolution Measurement of the Glycolytic Rate

PubMed Central

Bittner, Carla X.; Loaiza, Anitsi; Ruminot, Iván; Larenas, Valeria; Sotelo-Hitschfeld, Tamara; Gutiérrez, Robin; Córdova, Alex; Valdebenito, Rocío; Frommer, Wolf B.; Barros, L. Felipe

2010-01-01

The glycolytic rate is sensitive to physiological activity, hormones, stress, aging, and malignant transformation. Standard techniques to measure the glycolytic rate are based on radioactive isotopes, are not able to resolve single cells and have poor temporal resolution, limitations that hamper the study of energy metabolism in the brain and other organs. A new method is described in this article, which makes use of a recently developed FRET glucose nanosensor to measure the rate of glycolysis in single cells with high temporal resolution. Used in cultured astrocytes, the method showed for the first time that glycolysis can be activated within seconds by a combination of glutamate and K+, supporting a role for astrocytes in neurometabolic and neurovascular coupling in the brain. It was also possible to make a direct comparison of metabolism in neurons and astrocytes lying in close proximity, paving the way to a high-resolution characterization of brain energy metabolism. Single-cell glycolytic rates were also measured in fibroblasts, adipocytes, myoblasts, and tumor cells, showing higher rates for undifferentiated cells and significant metabolic heterogeneity within cell types. This method should facilitate the investigation of tissue metabolism at the single-cell level and is readily adaptable for high-throughput analysis. PMID:20890447

Individual Brain Charting, a high-resolution fMRI dataset for cognitive mapping.

PubMed

Pinho, Ana Luísa; Amadon, Alexis; Ruest, Torsten; Fabre, Murielle; Dohmatob, Elvis; Denghien, Isabelle; Ginisty, Chantal; Becuwe-Desmidt, Séverine; Roger, Séverine; Laurier, Laurence; Joly-Testault, Véronique; Médiouni-Cloarec, Gaëlle; Doublé, Christine; Martins, Bernadette; Pinel, Philippe; Eger, Evelyn; Varoquaux, Gaël; Pallier, Christophe; Dehaene, Stanislas; Hertz-Pannier, Lucie; Thirion, Bertrand

2018-06-12

Functional Magnetic Resonance Imaging (fMRI) has furthered brain mapping on perceptual, motor, as well as higher-level cognitive functions. However, to date, no data collection has systematically addressed the functional mapping of cognitive mechanisms at a fine spatial scale. The Individual Brain Charting (IBC) project stands for a high-resolution multi-task fMRI dataset that intends to provide the objective basis toward a comprehensive functional atlas of the human brain. The data refer to a cohort of 12 participants performing many different tasks. The large amount of task-fMRI data on the same subjects yields a precise mapping of the underlying functions, free from both inter-subject and inter-site variability. The present article gives a detailed description of the first release of the IBC dataset. It comprises a dozen of tasks, addressing both low- and high- level cognitive functions. This openly available dataset is thus intended to become a reference for cognitive brain mapping.

A cytoarchitecture-driven myelin model reveals area-specific signatures in human primary and secondary areas using ultra-high resolution in-vivo brain MRI.

PubMed

Dinse, J; Härtwich, N; Waehnert, M D; Tardif, C L; Schäfer, A; Geyer, S; Preim, B; Turner, R; Bazin, P-L

2015-07-01

This work presents a novel approach for modelling laminar myelin patterns in the human cortex in brain MR images on the basis of known cytoarchitecture. For the first time, it is possible to estimate intracortical contrast visible in quantitative ultra-high resolution MR images in specific primary and secondary cytoarchitectonic areas. The presented technique reveals different area-specific signatures which may help to study the spatial distribution of cortical T1 values and the distribution of cortical myelin in general. It may lead to a new discussion on the concordance of cyto- and myeloarchitectonic boundaries, given the absence of such concordance atlases. The modelled myelin patterns are quantitatively compared with data from human ultra-high resolution in-vivo 7T brain MR images (9 subjects). In the validation, the results are compared to one post-mortem brain sample and its ex-vivo MRI and histological data. Details of the analysis pipeline are provided. In the context of the increasing interest in advanced methods in brain segmentation and cortical architectural studies, the presented model helps to bridge the gap between the microanatomy revealed by classical histology and the macroanatomy visible in MRI. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Organic electronics for high-resolution electrocorticography of the human brain.

PubMed

Khodagholy, Dion; Gelinas, Jennifer N; Zhao, Zifang; Yeh, Malcolm; Long, Michael; Greenlee, Jeremy D; Doyle, Werner; Devinsky, Orrin; Buzsáki, György

2016-11-01

Localizing neuronal patterns that generate pathological brain signals may assist with tissue resection and intervention strategies in patients with neurological diseases. Precise localization requires high spatiotemporal recording from populations of neurons while minimizing invasiveness and adverse events. We describe a large-scale, high-density, organic material-based, conformable neural interface device ("NeuroGrid") capable of simultaneously recording local field potentials (LFPs) and action potentials from the cortical surface. We demonstrate the feasibility and safety of intraoperative recording with NeuroGrids in anesthetized and awake subjects. Highly localized and propagating physiological and pathological LFP patterns were recorded, and correlated neural firing provided evidence about their local generation. Application of NeuroGrids to brain disorders, such as epilepsy, may improve diagnostic precision and therapeutic outcomes while reducing complications associated with invasive electrodes conventionally used to acquire high-resolution and spiking data.

The Track of Brain Activity during the Observation of TV Commercials with the High-Resolution EEG Technology

PubMed Central

Astolfi, Laura; Vecchiato, Giovanni; De Vico Fallani, Fabrizio; Salinari, Serenella; Cincotti, Febo; Aloise, Fabio; Mattia, Donatella; Marciani, Maria Grazia; Bianchi, Luigi; Soranzo, Ramon; Babiloni, Fabio

2009-01-01

We estimate cortical activity in normal subjects during the observation of TV commercials inserted within a movie by using high-resolution EEG techniques. The brain activity was evaluated in both time and frequency domains by solving the associate inverse problem of EEG with the use of realistic head models. In particular, we recover statistically significant information about cortical areas engaged by particular scenes inserted within the TV commercial proposed with respect to the brain activity estimated while watching a documentary. Results obtained in the population investigated suggest that the statistically significant brain activity during the observation of the TV commercial was mainly concentrated in frontoparietal cortical areas, roughly coincident with the Brodmann areas 8, 9, and 7, in the analyzed population. PMID:19584910

Resting-state functional connectivity imaging of the mouse brain using photoacoustic tomography

NASA Astrophysics Data System (ADS)

Nasiriavanaki, Mohammadreza; Xia, Jun; Wan, Hanlin; Bauer, Adam Q.; Culver, Joseph P.; Wang, Lihong V.

2014-03-01

Resting-state functional connectivity (RSFC) imaging is an emerging neuroimaging approach that aims to identify spontaneous cerebral hemodynamic fluctuations and their associated functional connections. Clinical studies have demonstrated that RSFC is altered in brain disorders such as stroke, Alzheimer's, autism, and epilepsy. However, conventional neuroimaging modalities cannot easily be applied to mice, the most widely used model species for human brain disease studies. For instance, functional magnetic resonance imaging (fMRI) of mice requires a very high magnetic field to obtain a sufficient signal-to-noise ratio and spatial resolution. Functional connectivity mapping with optical intrinsic signal imaging (fcOIS) is an alternative method. Due to the diffusion of light in tissue, the spatial resolution of fcOIS is limited, and experiments have been performed using an exposed skull preparation. In this study, we show for the first time, the use of photoacoustic computed tomography (PACT) to noninvasively image resting-state functional connectivity in the mouse brain, with a large field of view and a high spatial resolution. Bilateral correlations were observed in eight regions, as well as several subregions. These findings agreed well with the Paxinos mouse brain atlas. This study showed that PACT is a promising, non-invasive modality for small-animal functional brain imaging.

Transcranial magnetic stimulation of mouse brain using high-resolution anatomical models

NASA Astrophysics Data System (ADS)

Crowther, L. J.; Hadimani, R. L.; Kanthasamy, A. G.; Jiles, D. C.

2014-05-01

Transcranial magnetic stimulation (TMS) offers the possibility of non-invasive treatment of brain disorders in humans. Studies on animals can allow rapid progress of the research including exploring a variety of different treatment conditions. Numerical calculations using animal models are needed to help design suitable TMS coils for use in animal experiments, in particular, to estimate the electric field induced in animal brains. In this paper, we have implemented a high-resolution anatomical MRI-derived mouse model consisting of 50 tissue types to accurately calculate induced electric field in the mouse brain. Magnetic field measurements have been performed on the surface of the coil and compared with the calculations in order to validate the calculated magnetic and induced electric fields in the brain. Results show how the induced electric field is distributed in a mouse brain and allow investigation of how this could be improved for TMS studies using mice. The findings have important implications in further preclinical development of TMS for treatment of human diseases.

Comparison of simultaneously recorded [H2(15)O]-PET and LORETA during cognitive and pharmacological activation.

PubMed

Gamma, Alex; Lehmann, Dietrich; Frei, Edi; Iwata, Kazuki; Pascual-Marqui, Roberto D; Vollenweider, Franz X

2004-06-01

The complementary strengths and weaknesses of established functional brain imaging methods (high spatial, low temporal resolution) and EEG-based techniques (low spatial, high temporal resolution) make their combined use a promising avenue for studying brain processes at a more fine-grained level. However, this strategy requires a better understanding of the relationship between hemodynamic/metabolic and neuroelectric measures of brain activity. We investigated possible correspondences between cerebral blood flow (CBF) as measured by [H2O]-PET and intracerebral electric activity computed by Low Resolution Brain Electromagnetic Tomography (LORETA) from scalp-recorded multichannel EEG in healthy human subjects during cognitive and pharmacological stimulation. The two imaging modalities were compared by descriptive, correlational, and variance analyses, the latter carried out using statistical parametric mapping (SPM99). Descriptive visual comparison showed a partial overlap between the sets of active brain regions detected by the two modalities. A number of exclusively positive correlations of neuroelectric activity with regional CBF were found across the whole EEG frequency range, including slow wave activity, the latter finding being in contrast to most previous studies conducted in patients. Analysis of variance revealed an extensive lack of statistically significant correspondences between brain activity changes as measured by PET vs. EEG-LORETA. In general, correspondences, to the extent they were found, were dependent on experimental condition, brain region, and EEG frequency. Copyright 2004 Wiley-Liss, Inc.

High-resolution detection of 13C multiplets from the conscious mouse brain by ex vivo NMR spectroscopy

PubMed Central

Marin-Valencia, Isaac; Good, Levi B.; Ma, Qian; Jeffrey, F. Mark; Malloy, Craig R.; Pascual, Juan M.

2011-01-01

Glucose readily supplies the brain with the majority of carbon needed to sustain neurotransmitter production and utilization., The rate of brain glucose metabolism can be computed using 13C nuclear magnetic resonance (NMR) spectroscopy by detecting changes in 13C contents of products generated by cerebral metabolism. As previously observed, scalar coupling between adjacent 13C carbons (multiplets) can provide additional information to 13C contents for the computation of metabolic rates. Most NMR studies have been conducted in large animals (often under anesthesia) because the mass of the target organ is a limiting factor for NMR. Yet, despite the challengingly small size of the mouse brain, NMR studies are highly desirable because the mouse constitutes a common animal model for human neurological disorders. We have developed a method for the ex vivo resolution of NMR multiplets arising from the brain of an awake mouse after the infusion of [1,6-13C2]glucose. NMR spectra obtained by this method display favorable signal-to-noise ratios. With this protocol, the 13C multiplets of glutamate, glutamine, GABA and aspartate achieved steady state after 150 min. The method enables the accurate resolution of multiplets over time in the awake mouse brain. We anticipate that this method can be broadly applicable to compute brain fluxes in normal and transgenic mouse models of neurological disorders. PMID:21946227

Conformable actively multiplexed high-density surface electrode array for brain interfacing

DOEpatents

Rogers, John; Kim, Dae-Hyeong; Litt, Brian; Viventi, Jonathan

2015-01-13

Provided are methods and devices for interfacing with brain tissue, specifically for monitoring and/or actuation of spatio-temporal electrical waveforms. The device is conformable having a high electrode density and high spatial and temporal resolution. A conformable substrate supports a conformable electronic circuit and a barrier layer. Electrodes are positioned to provide electrical contact with a brain tissue. A controller monitors or actuates the electrodes, thereby interfacing with the brain tissue. In an aspect, methods are provided to monitor or actuate spatio-temporal electrical waveform over large brain surface areas by any of the devices disclosed herein.

Exploring sex differences in the adult zebra finch brain: In vivo diffusion tensor imaging and ex vivo super-resolution track density imaging.

PubMed

Hamaide, Julie; De Groof, Geert; Van Steenkiste, Gwendolyn; Jeurissen, Ben; Van Audekerke, Johan; Naeyaert, Maarten; Van Ruijssevelt, Lisbeth; Cornil, Charlotte; Sijbers, Jan; Verhoye, Marleen; Van der Linden, Annemie

2017-02-01

Zebra finches are an excellent model to study the process of vocal learning, a complex socially-learned tool of communication that forms the basis of spoken human language. So far, structural investigation of the zebra finch brain has been performed ex vivo using invasive methods such as histology. These methods are highly specific, however, they strongly interfere with performing whole-brain analyses and exclude longitudinal studies aimed at establishing causal correlations between neuroplastic events and specific behavioral performances. Therefore, the aim of the current study was to implement an in vivo Diffusion Tensor Imaging (DTI) protocol sensitive enough to detect structural sex differences in the adult zebra finch brain. Voxel-wise comparison of male and female DTI parameter maps shows clear differences in several components of the song control system (i.e. Area X surroundings, the high vocal center (HVC) and the lateral magnocellular nucleus of the anterior nidopallium (LMAN)), which corroborate previous findings and are in line with the clear behavioral difference as only males sing. Furthermore, to obtain additional insights into the 3-dimensional organization of the zebra finch brain and clarify findings obtained by the in vivo study, ex vivo DTI data of the male and female brain were acquired as well, using a recently established super-resolution reconstruction (SRR) imaging strategy. Interestingly, the SRR-DTI approach led to a marked reduction in acquisition time without interfering with the (spatial and angular) resolution and SNR which enabled to acquire a data set characterized by a 78μm isotropic resolution including 90 diffusion gradient directions within 44h of scanning time. Based on the reconstructed SRR-DTI maps, whole brain probabilistic Track Density Imaging (TDI) was performed for the purpose of super resolved track density imaging, further pushing the resolution up to 40μm isotropic. The DTI and TDI maps realized atlas-quality anatomical maps that enable a clear delineation of most components of the song control and auditory systems. In conclusion, this study paves the way for longitudinal in vivo and high-resolution ex vivo experiments aimed at disentangling neuroplastic events that characterize the critical period for vocal learning in zebra finch ontogeny. Copyright © 2016 Elsevier Inc. All rights reserved.

Time-efficient high-resolution whole-brain three-dimensional macromolecular proton fraction mapping

PubMed Central

Yarnykh, Vasily L.

2015-01-01

Purpose Macromolecular proton fraction (MPF) mapping is a quantitative MRI method that reconstructs parametric maps of a relative amount of macromolecular protons causing the magnetization transfer (MT) effect and provides a biomarker of myelination in neural tissues. This study aimed to develop a high-resolution whole-brain MPF mapping technique utilizing a minimal possible number of source images for scan time reduction. Methods The described technique is based on replacement of an actually acquired reference image without MT saturation by a synthetic one reconstructed from R1 and proton density maps, thus requiring only three source images. This approach enabled whole-brain three-dimensional MPF mapping with isotropic 1.25×1.25×1.25 mm3 voxel size and scan time of 20 minutes. The synthetic reference method was validated against standard MPF mapping with acquired reference images based on data from 8 healthy subjects. Results Mean MPF values in segmented white and gray matter appeared in close agreement with no significant bias and small within-subject coefficients of variation (<2%). High-resolution MPF maps demonstrated sharp white-gray matter contrast and clear visualization of anatomical details including gray matter structures with high iron content. Conclusions Synthetic reference method improves resolution of MPF mapping and combines accurate MPF measurements with unique neuroanatomical contrast features. PMID:26102097

High-resolution EEG (HR-EEG) and magnetoencephalography (MEG).

PubMed

Gavaret, M; Maillard, L; Jung, J

2015-03-01

High-resolution EEG (HR-EEG) and magnetoencephalography (MEG) allow the recording of spontaneous or evoked electromagnetic brain activity with excellent temporal resolution. Data must be recorded with high temporal resolution (sampling rate) and high spatial resolution (number of channels). Data analyses are based on several steps with selection of electromagnetic signals, elaboration of a head model and use of algorithms in order to solve the inverse problem. Due to considerable technical advances in spatial resolution, these tools now represent real methods of ElectroMagnetic Source Imaging. HR-EEG and MEG constitute non-invasive and complementary examinations, characterized by distinct sensitivities according to the location and orientation of intracerebral generators. In the presurgical assessment of drug-resistant partial epilepsies, HR-EEG and MEG can characterize and localize interictal activities and thus the irritative zone. HR-EEG and MEG often yield significant additional data that are complementary to other presurgical investigations and particularly relevant in MRI-negative cases. Currently, the determination of the epileptogenic zone and functional brain mapping remain rather less well-validated indications. In France, in 2014, HR-EEG is now part of standard clinical investigation of epilepsy, while MEG remains a research technique. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

High-throughput dual-colour precision imaging for brain-wide connectome with cytoarchitectonic landmarks at the cellular level

PubMed Central

Gong, Hui; Xu, Dongli; Yuan, Jing; Li, Xiangning; Guo, Congdi; Peng, Jie; Li, Yuxin; Schwarz, Lindsay A.; Li, Anan; Hu, Bihe; Xiong, Benyi; Sun, Qingtao; Zhang, Yalun; Liu, Jiepeng; Zhong, Qiuyuan; Xu, Tonghui; Zeng, Shaoqun; Luo, Qingming

2016-01-01

The precise annotation and accurate identification of neural structures are prerequisites for studying mammalian brain function. The orientation of neurons and neural circuits is usually determined by mapping brain images to coarse axial-sampling planar reference atlases. However, individual differences at the cellular level likely lead to position errors and an inability to orient neural projections at single-cell resolution. Here, we present a high-throughput precision imaging method that can acquire a co-localized brain-wide data set of both fluorescent-labelled neurons and counterstained cell bodies at a voxel size of 0.32 × 0.32 × 2.0 μm in 3 days for a single mouse brain. We acquire mouse whole-brain imaging data sets of multiple types of neurons and projections with anatomical annotation at single-neuron resolution. The results show that the simultaneous acquisition of labelled neural structures and cytoarchitecture reference in the same brain greatly facilitates precise tracing of long-range projections and accurate locating of nuclei. PMID:27374071

Embedding and Chemical Reactivation of Green Fluorescent Protein in the Whole Mouse Brain for Optical Micro-Imaging

PubMed Central

Gang, Yadong; Zhou, Hongfu; Jia, Yao; Liu, Ling; Liu, Xiuli; Rao, Gong; Li, Longhui; Wang, Xiaojun; Lv, Xiaohua; Xiong, Hanqing; Yang, Zhongqin; Luo, Qingming; Gong, Hui; Zeng, Shaoqun

2017-01-01

Resin embedding has been widely applied to fixing biological tissues for sectioning and imaging, but has long been regarded as incompatible with green fluorescent protein (GFP) labeled sample because it reduces fluorescence. Recently, it has been reported that resin-embedded GFP-labeled brain tissue can be imaged with high resolution. In this protocol, we describe an optimized protocol for resin embedding and chemical reactivation of fluorescent protein labeled mouse brain, we have used mice as experiment model, but the protocol should be applied to other species. This method involves whole brain embedding and chemical reactivation of the fluorescent signal in resin-embedded tissue. The whole brain embedding process takes a total of 7 days. The duration of chemical reactivation is ~2 min for penetrating 4 μm below the surface in the resin-embedded brain. This protocol provides an efficient way to prepare fluorescent protein labeled sample for high-resolution optical imaging. This kind of sample was demonstrated to be imaged by various optical micro-imaging methods. Fine structures labeled with GFP across a whole brain can be detected. PMID:28352214

Micromirror structured illumination microscope for high-speed in vivo drosophila brain imaging.

PubMed

Masson, A; Pedrazzani, M; Benrezzak, S; Tchenio, P; Preat, T; Nutarelli, D

2014-01-27

Genetic tools and especially genetically encoded fluorescent reporters have given a special place to optical microscopy in drosophila neurobiology research. In order to monitor neural networks activity, high speed and sensitive techniques, with high spatial resolution are required. Structured illumination microscopies are wide-field approaches with optical sectioning ability. Despite the large progress made with the introduction of the HiLo principle, they did not meet the criteria of speed and/or spatial resolution for drosophila brain imaging. We report on a new implementation that took advantage of micromirror matrix technology to structure the illumination. Thus, we showed that the developed instrument exhibits a spatial resolution close to that of confocal microscopy but it can record physiological responses with a speed improved by more than an order a magnitude.

Open Science CBS Neuroimaging Repository: Sharing ultra-high-field MR images of the brain.

PubMed

Tardif, Christine Lucas; Schäfer, Andreas; Trampel, Robert; Villringer, Arno; Turner, Robert; Bazin, Pierre-Louis

2016-01-01

Magnetic resonance imaging at ultra high field opens the door to quantitative brain imaging at sub-millimeter isotropic resolutions. However, novel image processing tools to analyze these new rich datasets are lacking. In this article, we introduce the Open Science CBS Neuroimaging Repository: a unique repository of high-resolution and quantitative images acquired at 7 T. The motivation for this project is to increase interest for high-resolution and quantitative imaging and stimulate the development of image processing tools developed specifically for high-field data. Our growing repository currently includes datasets from MP2RAGE and multi-echo FLASH sequences from 28 and 20 healthy subjects respectively. These datasets represent the current state-of-the-art in in-vivo relaxometry at 7 T, and are now fully available to the entire neuroimaging community. Copyright © 2015 Elsevier Inc. All rights reserved.

First multiphoton tomography of brain in man

NASA Astrophysics Data System (ADS)

König, Karsten; Kantelhardt, Sven R.; Kalasauskas, Darius; Kim, Ella; Giese, Alf

2016-03-01

We report on the first two-photon in vivo brain tissue imaging study in man. High resolution in vivo histology by multiphoton tomography (MPT) including two-photon FLIM was performed in the operation theatre during neurosurgery to evaluate the feasibility to detect label-free tumor borders with subcellular resolution. This feasibility study demonstrates, that MPT has the potential to identify tumor borders on a cellular level in nearly real-time.

High-resolution x-ray absorption spectroscopy studies of metal compounds in neurodegenerative brain tissue

NASA Astrophysics Data System (ADS)

Collingwood, J. F.; Mikhaylova, A.; Davidson, M. R.; Batich, C.; Streit, W. J.; Eskin, T.; Terry, J.; Barrea, R.; Underhill, R. S.; Dobson, J.

2005-01-01

Fluorescence mapping and microfocus X-ray absorption spectroscopy are used to detect, locate and identify iron biominerals and other inorganic metal accumulations in neurodegenerative brain tissue at sub-cellular resolution (<5 microns). Recent progress in developing the technique is reviewed. Synchrotron X-rays are used to map tissue sections for metals of interest, and XANES and XAFS are used to characterise anomalous concentrations of the metals in-situ so that they can be correlated with tissue structures and disease pathology. Iron anomalies associated with biogenic magnetite, ferritin and haemoglobin are located and identified in an avian tissue model with a pixel resolution ~5 microns. Subsequent studies include brain tissue sections from transgenic Huntington's mice, and the first high-resolution mapping and identification of iron biominerals in human Alzheimer's and control autopsy brain tissue. Technical developments include use of microfocus diffraction to obtain structural information about biominerals in-situ, and depositing sample location grids by lithography for the location of anomalies by conventional microscopy. The combined techniques provide a breakthrough in the study of both intra- and extra-cellular iron compounds and related metals in tissue. The information to be gained from this approach has implications for future diagnosis and treatment of neurodegeneration, and for our understanding of the mechanisms involved.

In vivo High Angular Resolution Diffusion-Weighted Imaging of Mouse Brain at 16.4 Tesla

PubMed Central

Alomair, Othman I.; Brereton, Ian M.; Smith, Maree T.; Galloway, Graham J.; Kurniawan, Nyoman D.

2015-01-01

Magnetic Resonance Imaging (MRI) of the rodent brain at ultra-high magnetic fields (> 9.4 Tesla) offers a higher signal-to-noise ratio that can be exploited to reduce image acquisition time or provide higher spatial resolution. However, significant challenges are presented due to a combination of longer T 1 and shorter T 2/T2* relaxation times and increased sensitivity to magnetic susceptibility resulting in severe local-field inhomogeneity artefacts from air pockets and bone/brain interfaces. The Stejskal-Tanner spin echo diffusion-weighted imaging (DWI) sequence is often used in high-field rodent brain MRI due to its immunity to these artefacts. To accurately determine diffusion-tensor or fibre-orientation distribution, high angular resolution diffusion imaging (HARDI) with strong diffusion weighting (b >3000 s/mm2) and at least 30 diffusion-encoding directions are required. However, this results in long image acquisition times unsuitable for live animal imaging. In this study, we describe the optimization of HARDI acquisition parameters at 16.4T using a Stejskal-Tanner sequence with echo-planar imaging (EPI) readout. EPI segmentation and partial Fourier encoding acceleration were applied to reduce the echo time (TE), thereby minimizing signal decay and distortion artefacts while maintaining a reasonably short acquisition time. The final HARDI acquisition protocol was achieved with the following parameters: 4 shot EPI, b = 3000 s/mm2, 64 diffusion-encoding directions, 125×150 μm2 in-plane resolution, 0.6 mm slice thickness, and 2h acquisition time. This protocol was used to image a cohort of adult C57BL/6 male mice, whereby the quality of the acquired data was assessed and diffusion tensor imaging (DTI) derived parameters were measured. High-quality images with high spatial and angular resolution, low distortion and low variability in DTI-derived parameters were obtained, indicating that EPI-DWI is feasible at 16.4T to study animal models of white matter (WM) diseases. PMID:26110770

Super-resolution Imaging of Chemical Synapses in the Brain

PubMed Central

Dani, Adish; Huang, Bo; Bergan, Joseph; Dulac, Catherine; Zhuang, Xiaowei

2010-01-01

Determination of the molecular architecture of synapses requires nanoscopic image resolution and specific molecular recognition, a task that has so far defied many conventional imaging approaches. Here we present a super-resolution fluorescence imaging method to visualize the molecular architecture of synapses in the brain. Using multicolor, three-dimensional stochastic optical reconstruction microscopy, the distributions of synaptic proteins can be measured with nanometer precision. Furthermore, the wide-field, volumetric imaging method enables high-throughput, quantitative analysis of a large number of synapses from different brain regions. To demonstrate the capabilities of this approach, we have determined the organization of ten protein components of the presynaptic active zone and the postsynaptic density. Variations in synapse morphology, neurotransmitter receptor composition, and receptor distribution were observed both among synapses and across different brain regions. Combination with optogenetics further allowed molecular events associated with synaptic plasticity to be resolved at the single-synapse level. PMID:21144999

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wu, Pei-Hsin; Chung, Hsiao-Wen; Tsai, Ping-Huei

Purpose: One of the technical advantages of functional magnetic resonance imaging (fMRI) is its precise localization of changes from neuronal activities. While current practice of fMRI acquisition at voxel size around 3 × 3 × 3 mm{sup 3} achieves satisfactory results in studies of basic brain functions, higher spatial resolution is required in order to resolve finer cortical structures. This study investigated spatial resolution effects on brain fMRI experiments using balanced steady-state free precession (bSSFP) imaging with 0.37 mm{sup 3} voxel volume at 3.0 T. Methods: In fMRI experiments, full and unilateral visual field 5 Hz flashing checkerboard stimulations weremore » given to healthy subjects. The bSSFP imaging experiments were performed at three different frequency offsets to widen the coverage, with functional activations in the primary visual cortex analyzed using the general linear model. Variations of the spatial resolution were achieved by removing outerk-space data components. Results: Results show that a reduction in voxel volume from 3.44 × 3.44 × 2 mm{sup 3} to 0.43 × 0.43 × 2 mm{sup 3} has resulted in an increase of the functional activation signals from (7.7 ± 1.7)% to (20.9 ± 2.0)% at 3.0 T, despite of the threefold SNR decreases in the original images, leading to nearly invariant functional contrast-to-noise ratios (fCNR) even at high spatial resolution. Activation signals aligning nicely with gray matter sulci at high spatial resolution would, on the other hand, have possibly been mistaken as noise at low spatial resolution. Conclusions: It is concluded that the bSSFP sequence is a plausible technique for fMRI investigations at submillimeter voxel widths without compromising fCNR. The reduction of partial volume averaging with nonactivated brain tissues to retain fCNR is uniquely suitable for high spatial resolution applications such as the resolving of columnar organization in the brain.« less

A super-resolution ultrasound method for brain vascular mapping

PubMed Central

O'Reilly, Meaghan A.; Hynynen, Kullervo

2013-01-01

Purpose: High-resolution vascular imaging has not been achieved in the brain due to limitations of current clinical imaging modalities. The authors present a method for transcranial ultrasound imaging of single micrometer-size bubbles within a tube phantom. Methods: Emissions from single bubbles within a tube phantom were mapped through an ex vivo human skull using a sparse hemispherical receiver array and a passive beamforming algorithm. Noninvasive phase and amplitude correction techniques were applied to compensate for the aberrating effects of the skull bone. The positions of the individual bubbles were estimated beyond the diffraction limit of ultrasound to produce a super-resolution image of the tube phantom, which was compared with microcomputed tomography (micro-CT). Results: The resulting super-resolution ultrasound image is comparable to results obtained via the micro-CT for small tissue specimen imaging. Conclusions: This method provides superior resolution to deep-tissue contrast ultrasound and has the potential to be extended to provide complete vascular network imaging in the brain. PMID:24320408

A wireless beta-microprobe based on pixelated silicon for in vivo brain studies in freely moving rats

NASA Astrophysics Data System (ADS)

Märk, J.; Benoit, D.; Balasse, L.; Benoit, M.; Clémens, J. C.; Fieux, S.; Fougeron, D.; Graber-Bolis, J.; Janvier, B.; Jevaud, M.; Genoux, A.; Gisquet-Verrier, P.; Menouni, M.; Pain, F.; Pinot, L.; Tourvielle, C.; Zimmer, L.; Morel, C.; Laniece, P.

2013-07-01

The investigation of neurophysiological mechanisms underlying the functional specificity of brain regions requires the development of technologies that are well adjusted to in vivo studies in small animals. An exciting challenge remains the combination of brain imaging and behavioural studies, which associates molecular processes of neuronal communications to their related actions. A pixelated intracerebral probe (PIXSIC) presents a novel strategy using a submillimetric probe for beta+ radiotracer detection based on a pixelated silicon diode that can be stereotaxically implanted in the brain region of interest. This fully autonomous detection system permits time-resolved high sensitivity measurements of radiotracers with additional imaging features in freely moving rats. An application-specific integrated circuit (ASIC) allows for parallel signal processing of each pixel and enables the wireless operation. All components of the detector were tested and characterized. The beta+ sensitivity of the system was determined with the probe dipped into radiotracer solutions. Monte Carlo simulations served to validate the experimental values and assess the contribution of gamma noise. Preliminary implantation tests on anaesthetized rats proved PIXSIC's functionality in brain tissue. High spatial resolution allows for the visualization of radiotracer concentration in different brain regions with high temporal resolution.

In vivo multiphoton tomography and fluorescence lifetime imaging of human brain tumor tissue.

PubMed

Kantelhardt, Sven R; Kalasauskas, Darius; König, Karsten; Kim, Ella; Weinigel, Martin; Uchugonova, Aisada; Giese, Alf

2016-05-01

High resolution multiphoton tomography and fluorescence lifetime imaging differentiates glioma from adjacent brain in native tissue samples ex vivo. Presently, multiphoton tomography is applied in clinical dermatology and experimentally. We here present the first application of multiphoton and fluorescence lifetime imaging for in vivo imaging on humans during a neurosurgical procedure. We used a MPTflex™ Multiphoton Laser Tomograph (JenLab, Germany). We examined cultured glioma cells in an orthotopic mouse tumor model and native human tissue samples. Finally the multiphoton tomograph was applied to provide optical biopsies during resection of a clinical case of glioblastoma. All tissues imaged by multiphoton tomography were sampled and processed for conventional histopathology. The multiphoton tomograph allowed fluorescence intensity- and fluorescence lifetime imaging with submicron spatial resolution and 200 picosecond temporal resolution. Morphological fluorescence intensity imaging and fluorescence lifetime imaging of tumor-bearing mouse brains and native human tissue samples clearly differentiated tumor and adjacent brain tissue. Intraoperative imaging was found to be technically feasible. Intraoperative image quality was comparable to ex vivo examinations. To our knowledge we here present the first intraoperative application of high resolution multiphoton tomography and fluorescence lifetime imaging of human brain tumors in situ. It allowed in vivo identification and determination of cell density of tumor tissue on a cellular and subcellular level within seconds. The technology shows the potential of rapid intraoperative identification of native glioma tissue without need for tissue processing or staining.

Disrupted Cerebro-cerebellar Intrinsic Functional Connectivity in Young Adults with High-functioning Autism Spectrum Disorder: A Data-driven, Whole-brain, High Temporal Resolution fMRI Study.

PubMed

Arnold Anteraper, Sheeba; Guell, Xavier; D'Mello, Anila; Joshi, Neha; Whitfield-Gabrieli, Susan; Joshi, Gagan

2018-06-13

To examine the resting-state functional-connectivity (RsFc) in young adults with high-functioning autism spectrum disorder (HF-ASD) using state-of-the-art fMRI data acquisition and analysis techniques. Simultaneous multi-slice, high temporal resolution fMRI acquisition; unbiased whole-brain connectome-wide multivariate pattern analysis (MVPA) techniques for assessing RsFc; and post-hoc whole-brain seed-to-voxel analyses using MVPA results as seeds. MVPA revealed two clusters of abnormal connectivity in the cerebellum. Whole-brain seed-based functional connectivity analyses informed by MVPA-derived clusters showed significant under connectivity between the cerebellum and social, emotional, and language brain regions in the HF-ASD group compared to healthy controls. The results we report are coherent with existing structural, functional, and RsFc literature in autism, extend previous literature reporting cerebellar abnormalities in the neuropathology of autism, and highlight the cerebellum as a potential target for therapeutic, diagnostic, predictive, and prognostic developments in ASD. The description of functional connectivity abnormalities using whole-brain, data-driven analyses as reported in the present study may crucially advance the development of ASD biomarkers, targets for therapeutic interventions, and neural predictors for measuring treatment response.

High and ultra-high resolution metabolite mapping of the human brain using 1H FID MRSI at 9.4T.

PubMed

Nassirpour, Sahar; Chang, Paul; Henning, Anke

2018-03-01

Magnetic resonance spectroscopic imaging (MRSI) is a promising technique for mapping the spatial distribution of multiple metabolites in the human brain. These metabolite maps can be used as a diagnostic tool to gain insight into several biochemical processes and diseases in the brain. In comparison to lower field strengths, MRSI at ultra-high field strengths benefits from a higher signal to noise ratio (SNR) as well as higher chemical shift dispersion, and hence spectral resolution. This study combines the benefits of an ultra-high field magnet with the advantages of an ultra-short TE and TR single-slice FID-MRSI sequence (such as negligible J-evolution and loss of SNR due to T 2 relaxation effects) and presents the first metabolite maps acquired at 9.4T in the healthy human brain at both high (voxel size of 97.6µL) and ultra-high (voxel size of 24.4µL) spatial resolutions in a scan time of 11 and 46min respectively. In comparison to lower field strengths, more anatomically-detailed maps with higher SNR from a larger number of metabolites are shown. A total of 12 metabolites including glutamate (Glu), glutamine (Gln), N-acetyl-aspartyl-glutamate (NAAG), Gamma-aminobutyric acid (GABA) and glutathione (GSH) are reliably mapped. Comprehensive description of the methodology behind these maps is provided. Copyright © 2016 Elsevier Inc. All rights reserved.

Liquid Chromatography Combined with Mass Spectrometry Utilising High-Resolution, Exact Mass, and Multi-Stage Fragmentation for the Identification of Oxysterols in Rat Brain

PubMed Central

Karu, Kersti; Hornshaw, Martin; Woffendin, Gary; Bodin, Karl; Hamberg, Mats; Alvelius, Gunvor; Sjövall, Jan; Turton, John; Wang, Yuqin; Griffiths, William J.

2008-01-01

In man the brain accounts for about 20% of the body's free cholesterol, most of which is synthesised de novo in brain. To maintain cholesterol balance throughout life, cholesterol becomes metabolised to 24S-hydroxycholesterol principally in neurons. In mouse, rat, and probably human, metabolism to 24S-hydroxycholesterol accounts for about 50% of cholesterol turnover, however, the route by which the remainder is turned over has yet to be elucidated. Here we describe a novel liquid chromatography (LC) – multi-stage fragmentation mass spectrometry (MSn) methodology for the identification, with high sensitivity (low pg), of cholesterol metabolites in rat brain. The methodology includes derivatisation to enhance ionisation, exact mass analysis at high-resolution to identify potential metabolites, and LC-MS3 to allow their characterisation. 24S-Hydroxycholesterol was confirmed as a major oxysterol in rat brain, while other oxysterols identified for the first time in brain included 24,25-, 24,27-, 25,27-, 6,24, 7α,25-, and 7α,27-dihydroxycholesterols. In addition, 3β-hydroxy-5-oxo-5,6-secocholestan-6-al and its aldol, two molecules linked to amyloidogenesis of proteins, were characterised in rat brain. PMID:17251593

Three-dimensional inversion recovery manganese-enhanced MRI of mouse brain using super-resolution reconstruction to visualize nuclei involved in higher brain function.

PubMed

Poole, Dana S; Plenge, Esben; Poot, Dirk H J; Lakke, Egbert A J F; Niessen, Wiro J; Meijering, Erik; van der Weerd, Louise

2014-07-01

The visualization of activity in mouse brain using inversion recovery spin echo (IR-SE) manganese-enhanced MRI (MEMRI) provides unique contrast, but suffers from poor resolution in the slice-encoding direction. Super-resolution reconstruction (SRR) is a resolution-enhancing post-processing technique in which multiple low-resolution slice stacks are combined into a single volume of high isotropic resolution using computational methods. In this study, we investigated, first, whether SRR can improve the three-dimensional resolution of IR-SE MEMRI in the slice selection direction, whilst maintaining or improving the contrast-to-noise ratio of the two-dimensional slice stacks. Second, the contrast-to-noise ratio of SRR IR-SE MEMRI was compared with a conventional three-dimensional gradient echo (GE) acquisition. Quantitative experiments were performed on a phantom containing compartments of various manganese concentrations. The results showed that, with comparable scan times, the signal-to-noise ratio of three-dimensional GE acquisition is higher than that of SRR IR-SE MEMRI. However, the contrast-to-noise ratio between different compartments can be superior with SRR IR-SE MEMRI, depending on the chosen inversion time. In vivo experiments were performed in mice receiving manganese using an implanted osmotic pump. The results showed that SRR works well as a resolution-enhancing technique in IR-SE MEMRI experiments. In addition, the SRR image also shows a number of brain structures that are more clearly discernible from the surrounding tissues than in three-dimensional GE acquisition, including a number of nuclei with specific higher brain functions, such as memory, stress, anxiety and reward behavior. Copyright © 2014 John Wiley & Sons, Ltd.

Specimen preparation, imaging, and analysis protocols for knife-edge scanning microscopy.

PubMed

Choe, Yoonsuck; Mayerich, David; Kwon, Jaerock; Miller, Daniel E; Sung, Chul; Chung, Ji Ryang; Huffman, Todd; Keyser, John; Abbott, Louise C

2011-12-09

Major advances in high-throughput, high-resolution, 3D microscopy techniques have enabled the acquisition of large volumes of neuroanatomical data at submicrometer resolution. One of the first such instruments producing whole-brain-scale data is the Knife-Edge Scanning Microscope (KESM), developed and hosted in the authors' lab. KESM has been used to section and image whole mouse brains at submicrometer resolution, revealing the intricate details of the neuronal networks (Golgi), vascular networks (India ink), and cell body distribution (Nissl). The use of KESM is not restricted to the mouse nor the brain. We have successfully imaged the octopus brain, mouse lung, and rat brain. We are currently working on whole zebra fish embryos. Data like these can greatly contribute to connectomics research; to microcirculation and hemodynamic research; and to stereology research by providing an exact ground-truth. In this article, we will describe the pipeline, including specimen preparation (fixing, staining, and embedding), KESM configuration and setup, sectioning and imaging with the KESM, image processing, data preparation, and data visualization and analysis. The emphasis will be on specimen preparation and visualization/analysis of obtained KESM data. We expect the detailed protocol presented in this article to help broaden the access to KESM and increase its utilization.

Collimator Design for a Brain SPECT/MRI Insert

NASA Astrophysics Data System (ADS)

Salvado, Debora; Erlandsson, Kjell; Bousse, Alexandre; Occhipinti, Michele; Busca, Paolo; Fiorini, Carlo; Hutton, Brian F.

2015-08-01

This project's goal is to design a SPECT insert for a clinical MRI system for simultaneous brain SPECT/MR imaging, with a high-sensitivity collimator and high-resolution detectors. We have compared eight collimator designs, four multi-pinhole and four multi-slit slit-slat configurations. The collimation was designed for a system with 2 rings of 25 5 × 5 cm detectors. We introduce the concept of 1/2-pinhole and 1/2-slit, which are transaxially shared between two adjacent detectors. Analytical geometric efficiency was calculated for an activity distribution corresponding to a human brain and a range of intrinsic detector resolutions Ri and target resolutions Rt at the centre of the FOV. Noise-free data were simulated with and without depth-of-interaction (DOI) information, 0.8 mm Ri and 10 mm Rt FWHM, and reconstructed for uniform, Defrise, Derenzo, and Zubal brain phantoms. Comparing the multi-pinhole and multi-slit slit-slat collimators, the former gives better reconstructed uniformity and transaxial resolution, while the latter gives better axial resolution. Although the 2 ×2-pinhole and 2-slit designs give the highest sensitivities, they result in a sub-optimal utilisation of the detector FOV. The best options are therefore the 5+ 2 1/2-pinhole and the 1 + 2 1/2-slit systems, with sensitivities of 1.8 ×10-4 and 3.2 ×10-4, respectively. Noiseless brain phantom reconstructions with the multi-pinhole collimator are slightly superior as compared to slit-slat, in terms of symmetry and accuracy of the activity distribution, but the same is not true when noise is included. DOI information reduces artefacts and improves uniformity in geometric phantoms. Further evaluation is needed with prototype collimators.

PAGANI Toolkit: Parallel graph-theoretical analysis package for brain network big data.

PubMed

Du, Haixiao; Xia, Mingrui; Zhao, Kang; Liao, Xuhong; Yang, Huazhong; Wang, Yu; He, Yong

2018-05-01

The recent collection of unprecedented quantities of neuroimaging data with high spatial resolution has led to brain network big data. However, a toolkit for fast and scalable computational solutions is still lacking. Here, we developed the PArallel Graph-theoretical ANalysIs (PAGANI) Toolkit based on a hybrid central processing unit-graphics processing unit (CPU-GPU) framework with a graphical user interface to facilitate the mapping and characterization of high-resolution brain networks. Specifically, the toolkit provides flexible parameters for users to customize computations of graph metrics in brain network analyses. As an empirical example, the PAGANI Toolkit was applied to individual voxel-based brain networks with ∼200,000 nodes that were derived from a resting-state fMRI dataset of 624 healthy young adults from the Human Connectome Project. Using a personal computer, this toolbox completed all computations in ∼27 h for one subject, which is markedly less than the 118 h required with a single-thread implementation. The voxel-based functional brain networks exhibited prominent small-world characteristics and densely connected hubs, which were mainly located in the medial and lateral fronto-parietal cortices. Moreover, the female group had significantly higher modularity and nodal betweenness centrality mainly in the medial/lateral fronto-parietal and occipital cortices than the male group. Significant correlations between the intelligence quotient and nodal metrics were also observed in several frontal regions. Collectively, the PAGANI Toolkit shows high computational performance and good scalability for analyzing connectome big data and provides a friendly interface without the complicated configuration of computing environments, thereby facilitating high-resolution connectomics research in health and disease. © 2018 Wiley Periodicals, Inc.

A New Variational Method for Bias Correction and Its Applications to Rodent Brain Extraction.

PubMed

Chang, Huibin; Huang, Weimin; Wu, Chunlin; Huang, Su; Guan, Cuntai; Sekar, Sakthivel; Bhakoo, Kishore Kumar; Duan, Yuping

2017-03-01

Brain extraction is an important preprocessing step for further analysis of brain MR images. Significant intensity inhomogeneity can be observed in rodent brain images due to the high-field MRI technique. Unlike most existing brain extraction methods that require bias corrected MRI, we present a high-order and L 0 regularized variational model for bias correction and brain extraction. The model is composed of a data fitting term, a piecewise constant regularization and a smooth regularization, which is constructed on a 3-D formulation for medical images with anisotropic voxel sizes. We propose an efficient multi-resolution algorithm for fast computation. At each resolution layer, we solve an alternating direction scheme, all subproblems of which have the closed-form solutions. The method is tested on three T2 weighted acquisition configurations comprising a total of 50 rodent brain volumes, which are with the acquisition field strengths of 4.7 Tesla, 9.4 Tesla and 17.6 Tesla, respectively. On one hand, we compare the results of bias correction with N3 and N4 in terms of the coefficient of variations on 20 different tissues of rodent brain. On the other hand, the results of brain extraction are compared against manually segmented gold standards, BET, BSE and 3-D PCNN based on a number of metrics. With the high accuracy and efficiency, our proposed method can facilitate automatic processing of large-scale brain studies.

High resolution, MRI-based, segmented, computerized head phantom

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zubal, I.G.; Harrell, C.R.; Smith, E.O.

1999-01-01

The authors have created a high-resolution software phantom of the human brain which is applicable to voxel-based radiation transport calculations yielding nuclear medicine simulated images and/or internal dose estimates. A software head phantom was created from 124 transverse MRI images of a healthy normal individual. The transverse T2 slices, recorded in a 256x256 matrix from a GE Signa 2 scanner, have isotropic voxel dimensions of 1.5 mm and were manually segmented by the clinical staff. Each voxel of the phantom contains one of 62 index numbers designating anatomical, neurological, and taxonomical structures. The result is stored as a 256x256x128 bytemore » array. Internal volumes compare favorably to those described in the ICRP Reference Man. The computerized array represents a high resolution model of a typical human brain and serves as a voxel-based anthropomorphic head phantom suitable for computer-based modeling and simulation calculations. It offers an improved realism over previous mathematically described software brain phantoms, and creates a reference standard for comparing results of newly emerging voxel-based computations. Such voxel-based computations lead the way to developing diagnostic and dosimetry calculations which can utilize patient-specific diagnostic images. However, such individualized approaches lack fast, automatic segmentation schemes for routine use; therefore, the high resolution, typical head geometry gives the most realistic patient model currently available.« less

Flexible Neural Electrode Array Based-on Porous Graphene for Cortical Microstimulation and Sensing

NASA Astrophysics Data System (ADS)

Lu, Yichen; Lyu, Hongming; Richardson, Andrew G.; Lucas, Timothy H.; Kuzum, Duygu

2016-09-01

Neural sensing and stimulation have been the backbone of neuroscience research, brain-machine interfaces and clinical neuromodulation therapies for decades. To-date, most of the neural stimulation systems have relied on sharp metal microelectrodes with poor electrochemical properties that induce extensive damage to the tissue and significantly degrade the long-term stability of implantable systems. Here, we demonstrate a flexible cortical microelectrode array based on porous graphene, which is capable of efficient electrophysiological sensing and stimulation from the brain surface, without penetrating into the tissue. Porous graphene electrodes show superior impedance and charge injection characteristics making them ideal for high efficiency cortical sensing and stimulation. They exhibit no physical delamination or degradation even after 1 million biphasic stimulation cycles, confirming high endurance. In in vivo experiments with rodents, same array is used to sense brain activity patterns with high spatio-temporal resolution and to control leg muscles with high-precision electrical stimulation from the cortical surface. Flexible porous graphene array offers a minimally invasive but high efficiency neuromodulation scheme with potential applications in cortical mapping, brain-computer interfaces, treatment of neurological disorders, where high resolution and simultaneous recording and stimulation of neural activity are crucial.

SPED light sheet microscopy: fast mapping of biological system structure and function

PubMed Central

Tomer, Raju; Lovett-Barron, Matthew; Kauvar, Isaac; Andalman, Aaron; Burns, Vanessa M.; Sankaran, Sethuraman; Grosenick, Logan; Broxton, Michael; Yang, Samuel; Deisseroth, Karl

2016-01-01

The goal of understanding living nervous systems has driven interest in high-speed and large field-of-view volumetric imaging at cellular resolution. Light-sheet microscopy approaches have emerged for cellular-resolution functional brain imaging in small organisms such as larval zebrafish, but remain fundamentally limited in speed. Here we have developed SPED light sheet microscopy, which combines large volumetric field-of-view via an extended depth of field with the optical sectioning of light sheet microscopy, thereby eliminating the need to physically scan detection objectives for volumetric imaging. SPED enables scanning of thousands of volumes-per-second, limited only by camera acquisition rate, through the harnessing of optical mechanisms that normally result in unwanted spherical aberrations. We demonstrate capabilities of SPED microscopy by performing fast sub-cellular resolution imaging of CLARITY mouse brains and cellular-resolution volumetric Ca2+ imaging of entire zebrafish nervous systems. Together, SPED light sheet methods enable high-speed cellular-resolution volumetric mapping of biological system structure and function. PMID:26687363

Super-resolution imaging of subcortical white matter using stochastic optical reconstruction microscopy (STORM) and super-resolution optical fluctuation imaging (SOFI)

PubMed Central

Hainsworth, A. H.; Lee, S.; Patel, A.; Poon, W. W.; Knight, A. E.

2018-01-01

Aims The spatial resolution of light microscopy is limited by the wavelength of visible light (the ‘diffraction limit’, approximately 250 nm). Resolution of sub-cellular structures, smaller than this limit, is possible with super resolution methods such as stochastic optical reconstruction microscopy (STORM) and super-resolution optical fluctuation imaging (SOFI). We aimed to resolve subcellular structures (axons, myelin sheaths and astrocytic processes) within intact white matter, using STORM and SOFI. Methods Standard cryostat-cut sections of subcortical white matter from donated human brain tissue and from adult rat and mouse brain were labelled, using standard immunohistochemical markers (neurofilament-H, myelin-associated glycoprotein, glial fibrillary acidic protein, GFAP). Image sequences were processed for STORM (effective pixel size 8–32 nm) and for SOFI (effective pixel size 80 nm). Results In human, rat and mouse, subcortical white matter high-quality images for axonal neurofilaments, myelin sheaths and filamentous astrocytic processes were obtained. In quantitative measurements, STORM consistently underestimated width of axons and astrocyte processes (compared with electron microscopy measurements). SOFI provided more accurate width measurements, though with somewhat lower spatial resolution than STORM. Conclusions Super resolution imaging of intact cryo-cut human brain tissue is feasible. For quantitation, STORM can under-estimate diameters of thin fluorescent objects. SOFI is more robust. The greatest limitation for super-resolution imaging in brain sections is imposed by sample preparation. We anticipate that improved strategies to reduce autofluorescence and to enhance fluorophore performance will enable rapid expansion of this approach. PMID:28696566

Super-resolution imaging of subcortical white matter using stochastic optical reconstruction microscopy (STORM) and super-resolution optical fluctuation imaging (SOFI).

PubMed

Hainsworth, A H; Lee, S; Foot, P; Patel, A; Poon, W W; Knight, A E

2018-06-01

The spatial resolution of light microscopy is limited by the wavelength of visible light (the 'diffraction limit', approximately 250 nm). Resolution of sub-cellular structures, smaller than this limit, is possible with super resolution methods such as stochastic optical reconstruction microscopy (STORM) and super-resolution optical fluctuation imaging (SOFI). We aimed to resolve subcellular structures (axons, myelin sheaths and astrocytic processes) within intact white matter, using STORM and SOFI. Standard cryostat-cut sections of subcortical white matter from donated human brain tissue and from adult rat and mouse brain were labelled, using standard immunohistochemical markers (neurofilament-H, myelin-associated glycoprotein, glial fibrillary acidic protein, GFAP). Image sequences were processed for STORM (effective pixel size 8-32 nm) and for SOFI (effective pixel size 80 nm). In human, rat and mouse, subcortical white matter high-quality images for axonal neurofilaments, myelin sheaths and filamentous astrocytic processes were obtained. In quantitative measurements, STORM consistently underestimated width of axons and astrocyte processes (compared with electron microscopy measurements). SOFI provided more accurate width measurements, though with somewhat lower spatial resolution than STORM. Super resolution imaging of intact cryo-cut human brain tissue is feasible. For quantitation, STORM can under-estimate diameters of thin fluorescent objects. SOFI is more robust. The greatest limitation for super-resolution imaging in brain sections is imposed by sample preparation. We anticipate that improved strategies to reduce autofluorescence and to enhance fluorophore performance will enable rapid expansion of this approach. © 2017 British Neuropathological Society.

Integrating histology and MRI in the first digital brain of common squirrel monkey, Saimiri sciureus

NASA Astrophysics Data System (ADS)

Sun, Peizhen; Parvathaneni, Prasanna; Schilling, Kurt G.; Gao, Yurui; Janve, Vaibhav; Anderson, Adam; Landman, Bennett A.

2015-03-01

This effort is a continuation of development of a digital brain atlas of the common squirrel monkey, Saimiri sciureus, a New World monkey with functional and microstructural organization of central nervous system similar to that of humans. Here, we present the integration of histology with multi-modal magnetic resonance imaging (MRI) atlas constructed from the brain of an adult female squirrel monkey. The central concept of this work is to use block face photography to establish an intermediate common space in coordinate system which preserves the high resolution in-plane resolution of histology while enabling 3-D correspondence with MRI. In vivo MRI acquisitions include high resolution T2 structural imaging (300 μm isotropic) and low resolution diffusion tensor imaging (600 um isotropic). Ex vivo MRI acquisitions include high resolution T2 structural imaging and high resolution diffusion tensor imaging (both 300 μm isotropic). Cortical regions were manually annotated on the co-registered volumes based on published histological sections in-plane. We describe mapping of histology and MRI based data of the common squirrel monkey and construction of a viewing tool that enable online viewing of these datasets. The previously descried atlas MRI is used for its deformation to provide accurate conformation to the MRI, thus adding information at the histological level to the MRI volume. This paper presents the mapping of single 2D image slice in block face as a proof of concept and this can be extended to map the atlas space in 3D coordinate system as part of the future work and can be loaded to an XNAT system for further use.

Low cost light-sheet microscopy for whole brain imaging

NASA Astrophysics Data System (ADS)

Kumar, Manish; Nasenbeny, Jordan; Kozorovitskiy, Yevgenia

2018-02-01

Light-sheet microscopy has evolved as an indispensable tool in imaging biological samples. It can image 3D samples at fast speed, with high-resolution optical sectioning, and with reduced photobleaching effects. These properties make light-sheet microscopy ideal for imaging fluorophores in a variety of biological samples and organisms, e.g. zebrafish, drosophila, cleared mouse brains, etc. While most commercial turnkey light-sheet systems are expensive, the existing lower cost implementations, e.g. OpenSPIM, are focused on achieving high-resolution imaging of small samples or organisms like zebrafish. In this work, we substantially reduce the cost of light-sheet microscope system while targeting to image much larger samples, i.e. cleared mouse brains, at single-cell resolution. The expensive components of a lightsheet system - excitation laser, water-immersion objectives, and translation stage - are replaced with an incoherent laser diode, dry objectives, and a custom-built Arduino-controlled translation stage. A low-cost CUBIC protocol is used to clear fixed mouse brain samples. The open-source platforms of μManager and Fiji support image acquisition, processing, and visualization. Our system can easily be extended to multi-color light-sheet microscopy.

Performance evaluation of neuro-PET using silicon photomultipliers

NASA Astrophysics Data System (ADS)

Jung, Jiwoong; Choi, Yong; Jung, Jin Ho; Kim, Sangsu; Im, Ki Chun

2016-05-01

Recently, we have developed the second prototype Silicon photomultiplier (SiPM) based positron emission tomography (PET) scanner for human brain imaging. The PET system was comprised of detector block which consisted of 4×4 SiPMs and 4×4 Lutetium Yttrium Orthosilicate arrays, charge signal transmission method, high density position decoder circuit and FPGA-embedded ADC boards. The purpose of this study was to evaluate the performance of the newly developed neuro-PET system. The energy resolution, timing resolution, spatial resolution, sensitivity, stability of the photo-peak position and count rate performance were measured. Tomographic image of 3D Hoffman brain phantom was also acquired to evaluate imaging capability of the neuro-PET. The average energy and timing resolutions measured for 511 keV gamma rays were 17±0.1% and 3±0.3 ns, respectively. Spatial resolution and sensitivity at the center of field of view (FOV) were 3.1 mm and 0.8%, respectively. The average scatter fraction was 0.4 with an energy window of 350-650 keV. The maximum true count rate and maximum NECR were measured as 43.3 kcps and 6.5 kcps at an activity concentration of 16.7 kBq/ml and 5.5 kBq/ml, respectively. Long-term stability results show that there was no significant change in the photo-peak position, energy resolution and count rate for 60 days. Phantom imaging studies were performed and they demonstrated the feasibility for high quality brain imaging. The performance tests and imaging results indicate that the newly developed PET is useful for brain imaging studies, if the axial FOV is extended to improve the system sensitivity.

Phase-contrast tomography of neuronal tissues: from laboratory- to high resolution synchrotron CT

NASA Astrophysics Data System (ADS)

Töpperwien, Mareike; Krenkel, Martin; Müller, Kristin; Salditt, Tim

2016-10-01

Assessing the three-dimensional architecture of neuronal tissues with sub-cellular resolution presents a significant analytical challenge. Overcoming the limitations associated with serial slicing, phase-contrast x-ray tomography has the potential to contribute to this goal. Even compact laboratory CT at an optimized liquid-metal jet micro- focus source combined with suitable phase-retrieval algorithms and preparation protocols can yield renderings with single cell sensitivity in millimeter sized brain areas of mouse. Here, we show the capabilities of the setup by imaging a Golgi-Cox impregnated mouse brain. Towards higher resolution we extend these studies at our recently upgraded waveguide-based cone-beam holo-tomography instrument GINIX at DESY. This setup allows high resolution recordings with adjustable field of view and resolution, down to the voxel sizes in the range of a few ten nanometers. The recent results make us confident that important issues of neuronal connectivity can be addressed by these methods, and that 3D (virtual) histology with nanoscale resolution will become an attractive modality for neuroscience research.

High resolution MRI anatomy of the cat brain at 3 Tesla

PubMed Central

Gray-Edwards, Heather L.; Salibi, Nouha; Josephson, Eleanor M.; Hudson, Judith A.; Cox, Nancy R.; Randle, Ashley N.; McCurdy, Victoria J.; Bradbury, Allison M.; Wilson, Diane U.; Beyers, Ronald J.; Denney, Thomas S.; Martin, Douglas R.

2014-01-01

Background Feline models of neurologic diseases, such as lysosomal storage diseases, leukodystrophies, Parkinson’s disease, stroke and NeuroAIDS, accurately recreate many aspects of human disease allowing for comparative study of neuropathology and the testing of novel therapeutics. Here we describe in vivo visualization of fine structures within the feline brain that were previously only visible post mortem. New Method 3 Tesla MR images were acquired using T1-weighted (T1w) 3D magnetization-prepared rapid gradient echo (MPRAGE) sequence (0.4mm isotropic resolution) and T2-weighted (T2w) turbo spin echo (TSE) images (0.3×0.3×1 mm3 resolution). Anatomic structures were identified based on feline and canine histology. Results T2w high resolution MR images with detailed structural identification are provided in transverse, sagittal and dorsal planes. T1w MR images are provided electronically in three dimensions for unrestricted spatial evaluation. Comparison with Existing Methods Many areas of the feline brain previously unresolvable on MRI are clearly visible in three orientations, including the dentate, interpositus and fastigial cerebellar nuclei, cranial nerves, lateral geniculate nucleus, optic radiation, cochlea, caudal colliculus, temporal lobe, precuneus, spinocerebellar tract, vestibular nuclei, reticular formation, pyramids and rostral and middle cerebral arteries. Additionally, the feline brain is represented in 3 dimensions for the first time. Conclusions These data establish normal appearance of detailed anatomical structures of the feline brain, which provide reference when evaluating neurologic disease or testing efficacy of novel therapeutics in animal models. PMID:24525327

Texture analysis of high-resolution FLAIR images for TLE

NASA Astrophysics Data System (ADS)

Jafari-Khouzani, Kourosh; Soltanian-Zadeh, Hamid; Elisevich, Kost

2005-04-01

This paper presents a study of the texture information of high-resolution FLAIR images of the brain with the aim of determining the abnormality and consequently the candidacy of the hippocampus for temporal lobe epilepsy (TLE) surgery. Intensity and volume features of the hippocampus from FLAIR images of the brain have been previously shown to be useful in detecting the abnormal hippocampus in TLE. However, the small size of the hippocampus may limit the texture information. High-resolution FLAIR images show more details of the abnormal intensity variations of the hippocampi and therefore are more suitable for texture analysis. We study and compare the low and high-resolution FLAIR images of six epileptic patients. The hippocampi are segmented manually by an expert from T1-weighted MR images. Then the segmented regions are mapped on the corresponding FLAIR images for texture analysis. The 2-D wavelet transforms of the hippocampi are employed for feature extraction. We compare the ability of the texture features from regular and high-resolution FLAIR images to distinguish normal and abnormal hippocampi. Intracranial EEG results as well as surgery outcome are used as gold standard. The results show that the intensity variations of the hippocampus are related to the abnormalities in the TLE.

Transparent, Flexible, Low Noise Graphene Electrodes for Simultaneous Electrophysiology and Neuroimaging

PubMed Central

Kuzum, Duygu; Takano, Hajime; Shim, Euijae; Reed, Jason C; Juul, Halvor; Richardson, Andrew G.; de Vries, Julius; Bink, Hank; Dichter, Marc A.; Lucas, Timothy H.; Coulter, Douglas A.; Cubukcu, Ertugrul; Litt, Brian

2014-01-01

Calcium imaging is a versatile experimental approach capable of resolving single neurons with single-cell spatial resolution in the brain. Electrophysiological recordings provide high temporal, but limited spatial resolution, due to the geometrical inaccessibility of the brain. An approach that integrates the advantages of both techniques could provide new insights into functions of neural circuits. Here, we report a transparent, flexible neural electrode technology based on graphene, which enables simultaneous optical imaging and electrophysiological recording. We demonstrate that hippocampal slices can be imaged through transparent graphene electrodes by both confocal and two-photon microscopy without causing any light-induced artifacts in the electrical recordings. Graphene electrodes record high frequency bursting activity and slow synaptic potentials that are hard to resolve by multi-cellular calcium imaging. This transparent electrode technology may pave the way for high spatio-temporal resolution electrooptic mapping of the dynamic neuronal activity. PMID:25327632

Development of optical neuroimaging to detect drug-induced brain functional changes in vivo

NASA Astrophysics Data System (ADS)

Du, Congwu; Pan, Yingtian

2014-03-01

Deficits in prefrontal function play a crucial role in compulsive cocaine use, which is a hallmark of addiction. Dysfunction of the prefrontal cortex might result from effects of cocaine on neurons as well as from disruption of cerebral blood vessels. However, the mechanisms underlying cocaine's neurotoxic effects are not fully understood, partially due to technical limitations of current imaging techniques (e.g., PET, fMRI) to differentiate vascular from neuronal effects at sufficiently high temporal and spatial resolutions. We have recently developed a multimodal imaging platform which can simultaneously characterize the changes in cerebrovascular hemodynamics, hemoglobin oxygenation and intracellular calcium fluorescence for monitoring the effects of cocaine on the brain. Such a multimodality imaging technique (OFI) provides several uniquely important merits, including: 1) a large field-of-view, 2) high spatiotemporal resolutions, 3) quantitative 3D imaging of the cerebral blood flow (CBF) networks, 4) label-free imaging of hemodynamic changes, 5) separation of vascular compartments (e.g., arterial and venous vessels) and monitoring of cortical brain metabolic changes, 6) discrimination of cellular (neuronal) from vascular responses. These imaging features have been further advanced in combination with microprobes to form micro-OFI that allows quantification of drug effects on subcortical brain. In addition, our ultrahigh-resolution ODT (μODT) enables 3D microangiography and quantitative imaging of capillary CBF networks. These optical strategies have been used to investigate the effects of cocaine on brain physiology to facilitate the studies of brain functional changes induced by addictive substance to provide new insights into neurobiological effects of the drug on the brain.

Dye-Enhanced Multimodal Confocal Imaging of Brain Cancers

NASA Astrophysics Data System (ADS)

Wirth, Dennis; Snuderl, Matija; Sheth, Sameer; Curry, William; Yaroslavsky, Anna

2011-04-01

Background and Significance: Accurate high resolution intraoperative detection of brain tumors may result in improved patient survival and better quality of life. The goal of this study was to evaluate dye enhanced multimodal confocal imaging for discriminating normal and cancerous brain tissue. Materials and Methods: Fresh thick brain specimens were obtained from the surgeries. Normal and cancer tissues were investigated. Samples were stained in methylene blue and imaged. Reflectance and fluorescence signals were excited at 658nm. Fluorescence emission and polarization were registered from 670 nm to 710 nm. The system provided lateral resolution of 0.6 μm and axial resolution of 7 μm. Normal and cancer specimens exhibited distinctively different characteristics. H&E histopathology was processed from each imaged sample. Results and Conclusions: The analysis of normal and cancerous tissues indicated clear differences in appearance in both the reflectance and fluorescence responses. These results confirm the feasibility of multimodal confocal imaging for intraoperative detection of small cancer nests and cells.

Monitoring of injury induced brain regeneration of the adult zebrafish by using optical coherence tomography

NASA Astrophysics Data System (ADS)

Yuan, Zhen; Zhang, Jian

2018-02-01

The adult zebrafish has pronounced regenerative capacity of the brain, which makes it an ideal model organism of vertebrate biology for the investigation of recovery of central nervous system injuries. The aim of this study was to employ spectral-domain optical coherence tomography (SD-OCT) system for long-term in vivo monitoring of tissue regeneration using an adult zebrafish model of brain injury. Based on a 1325 nm light source and two high-speed galvo mirrors, the SD-OCT system can offer a large field of view of the three-dimensional (3D) brain structures with high imaging resolution (12 μm axial and 13 μm lateral) at video rate. In vivo experiments based on this system were conducted to monitor the regeneration process of zebrafish brain after injury during a period of 43 days. To monitor and detect the process of tissue regeneration, we performed 3D in vivo imaging in a zebrafish model of adult brain injury during a period of 43 days. The coronal and sagittal views of the injured zebrafish brain at each time point (0 days, 10 days, 20 days and 43 days postlesion) were presented to show the changes of the brain lesion in detail. In addition, the 3D SD-OCT images for an injured zebrafish brain were also reconstructed at days 0 and days 43 post-lesion. We found that SD-OCT is able to effectively and noninvasively monitor the regeneration of the adult zebrafish brain after injury in real time with high 3D spatial resolution and good penetration depth. Our findings also suggested that the adult zebrafish has the extraordinary capability of brain regeneration and is able to repair itself after brain injury.

Effects of the murine skull in optoacoustic brain microscopy.

PubMed

Kneipp, Moritz; Turner, Jake; Estrada, Héctor; Rebling, Johannes; Shoham, Shy; Razansky, Daniel

2016-01-01

Despite the great promise behind the recent introduction of optoacoustic technology into the arsenal of small-animal neuroimaging methods, a variety of acoustic and light-related effects introduced by adult murine skull severely compromise the performance of optoacoustics in transcranial imaging. As a result, high-resolution noninvasive optoacoustic microscopy studies are still limited to a thin layer of pial microvasculature, which can be effectively resolved by tight focusing of the excitation light. We examined a range of distortions introduced by an adult murine skull in transcranial optoacoustic imaging under both acoustically- and optically-determined resolution scenarios. It is shown that strong low-pass filtering characteristics of the skull may significantly deteriorate the achievable spatial resolution in deep brain imaging where no light focusing is possible. While only brain vasculature with a diameter larger than 60 µm was effectively resolved via transcranial measurements with acoustic resolution, significant improvements are seen through cranial windows and thinned skull experiments. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Whole-brain serial-section electron microscopy in larval zebrafish.

PubMed

Hildebrand, David Grant Colburn; Cicconet, Marcelo; Torres, Russel Miguel; Choi, Woohyuk; Quan, Tran Minh; Moon, Jungmin; Wetzel, Arthur Willis; Scott Champion, Andrew; Graham, Brett Jesse; Randlett, Owen; Plummer, George Scott; Portugues, Ruben; Bianco, Isaac Henry; Saalfeld, Stephan; Baden, Alexander David; Lillaney, Kunal; Burns, Randal; Vogelstein, Joshua Tzvi; Schier, Alexander Franz; Lee, Wei-Chung Allen; Jeong, Won-Ki; Lichtman, Jeff William; Engert, Florian

2017-05-18

High-resolution serial-section electron microscopy (ssEM) makes it possible to investigate the dense meshwork of axons, dendrites, and synapses that form neuronal circuits. However, the imaging scale required to comprehensively reconstruct these structures is more than ten orders of magnitude smaller than the spatial extents occupied by networks of interconnected neurons, some of which span nearly the entire brain. Difficulties in generating and handling data for large volumes at nanoscale resolution have thus restricted vertebrate studies to fragments of circuits. These efforts were recently transformed by advances in computing, sample handling, and imaging techniques, but high-resolution examination of entire brains remains a challenge. Here, we present ssEM data for the complete brain of a larval zebrafish (Danio rerio) at 5.5 days post-fertilization. Our approach utilizes multiple rounds of targeted imaging at different scales to reduce acquisition time and data management requirements. The resulting dataset can be analysed to reconstruct neuronal processes, permitting us to survey all myelinated axons (the projectome). These reconstructions enable precise investigations of neuronal morphology, which reveal remarkable bilateral symmetry in myelinated reticulospinal and lateral line afferent axons. We further set the stage for whole-brain structure-function comparisons by co-registering functional reference atlases and in vivo two-photon fluorescence microscopy data from the same specimen. All obtained images and reconstructions are provided as an open-access resource.

Whole-brain serial-section electron microscopy in larval zebrafish

NASA Astrophysics Data System (ADS)

Hildebrand, David Grant Colburn; Cicconet, Marcelo; Torres, Russel Miguel; Choi, Woohyuk; Quan, Tran Minh; Moon, Jungmin; Wetzel, Arthur Willis; Scott Champion, Andrew; Graham, Brett Jesse; Randlett, Owen; Plummer, George Scott; Portugues, Ruben; Bianco, Isaac Henry; Saalfeld, Stephan; Baden, Alexander David; Lillaney, Kunal; Burns, Randal; Vogelstein, Joshua Tzvi; Schier, Alexander Franz; Lee, Wei-Chung Allen; Jeong, Won-Ki; Lichtman, Jeff William; Engert, Florian

2017-05-01

High-resolution serial-section electron microscopy (ssEM) makes it possible to investigate the dense meshwork of axons, dendrites, and synapses that form neuronal circuits. However, the imaging scale required to comprehensively reconstruct these structures is more than ten orders of magnitude smaller than the spatial extents occupied by networks of interconnected neurons, some of which span nearly the entire brain. Difficulties in generating and handling data for large volumes at nanoscale resolution have thus restricted vertebrate studies to fragments of circuits. These efforts were recently transformed by advances in computing, sample handling, and imaging techniques, but high-resolution examination of entire brains remains a challenge. Here, we present ssEM data for the complete brain of a larval zebrafish (Danio rerio) at 5.5 days post-fertilization. Our approach utilizes multiple rounds of targeted imaging at different scales to reduce acquisition time and data management requirements. The resulting dataset can be analysed to reconstruct neuronal processes, permitting us to survey all myelinated axons (the projectome). These reconstructions enable precise investigations of neuronal morphology, which reveal remarkable bilateral symmetry in myelinated reticulospinal and lateral line afferent axons. We further set the stage for whole-brain structure-function comparisons by co-registering functional reference atlases and in vivo two-photon fluorescence microscopy data from the same specimen. All obtained images and reconstructions are provided as an open-access resource.

Brain-heart interactions: challenges and opportunities with functional magnetic resonance imaging at ultra-high field.

PubMed

Chang, Catie; Raven, Erika P; Duyn, Jeff H

2016-05-13

Magnetic resonance imaging (MRI) at ultra-high field (UHF) strengths (7 T and above) offers unique opportunities for studying the human brain with increased spatial resolution, contrast and sensitivity. However, its reliability can be compromised by factors such as head motion, image distortion and non-neural fluctuations of the functional MRI signal. The objective of this review is to provide a critical discussion of the advantages and trade-offs associated with UHF imaging, focusing on the application to studying brain-heart interactions. We describe how UHF MRI may provide contrast and resolution benefits for measuring neural activity of regions involved in the control and mediation of autonomic processes, and in delineating such regions based on anatomical MRI contrast. Limitations arising from confounding signals are discussed, including challenges with distinguishing non-neural physiological effects from the neural signals of interest that reflect cardiorespiratory function. We also consider how recently developed data analysis techniques may be applied to high-field imaging data to uncover novel information about brain-heart interactions. © 2016 The Author(s).

Spatio-temporal reconstruction of brain dynamics from EEG with a Markov prior.

PubMed

Hansen, Sofie Therese; Hansen, Lars Kai

2017-03-01

Electroencephalography (EEG) can capture brain dynamics in high temporal resolution. By projecting the scalp EEG signal back to its origin in the brain also high spatial resolution can be achieved. Source localized EEG therefore has potential to be a very powerful tool for understanding the functional dynamics of the brain. Solving the inverse problem of EEG is however highly ill-posed as there are many more potential locations of the EEG generators than EEG measurement points. Several well-known properties of brain dynamics can be exploited to alleviate this problem. More short ranging connections exist in the brain than long ranging, arguing for spatially focal sources. Additionally, recent work (Delorme et al., 2012) argues that EEG can be decomposed into components having sparse source distributions. On the temporal side both short and long term stationarity of brain activation are seen. We summarize these insights in an inverse solver, the so-called "Variational Garrote" (Kappen and Gómez, 2013). Using a Markov prior we can incorporate flexible degrees of temporal stationarity. Through spatial basis functions spatially smooth distributions are obtained. Sparsity of these are inherent to the Variational Garrote solver. We name our method the MarkoVG and demonstrate its ability to adapt to the temporal smoothness and spatial sparsity in simulated EEG data. Finally a benchmark EEG dataset is used to demonstrate MarkoVG's ability to recover non-stationary brain dynamics. Copyright © 2016 Elsevier Inc. All rights reserved.

Regional Differences in Brain Volume Predict the Acquisition of Skill in a Complex Real-Time Strategy Videogame

ERIC Educational Resources Information Center

Basak, Chandramallika; Voss, Michelle W.; Erickson, Kirk I.; Boot, Walter R.; Kramer, Arthur F.

2011-01-01

Previous studies have found that differences in brain volume among older adults predict performance in laboratory tasks of executive control, memory, and motor learning. In the present study we asked whether regional differences in brain volume as assessed by the application of a voxel-based morphometry technique on high resolution MRI would also…

Segmenting Brain Tissues from Chinese Visible Human Dataset by Deep-Learned Features with Stacked Autoencoder

PubMed Central

Zhao, Guangjun; Wang, Xuchu; Niu, Yanmin; Tan, Liwen; Zhang, Shao-Xiang

2016-01-01

Cryosection brain images in Chinese Visible Human (CVH) dataset contain rich anatomical structure information of tissues because of its high resolution (e.g., 0.167 mm per pixel). Fast and accurate segmentation of these images into white matter, gray matter, and cerebrospinal fluid plays a critical role in analyzing and measuring the anatomical structures of human brain. However, most existing automated segmentation methods are designed for computed tomography or magnetic resonance imaging data, and they may not be applicable for cryosection images due to the imaging difference. In this paper, we propose a supervised learning-based CVH brain tissues segmentation method that uses stacked autoencoder (SAE) to automatically learn the deep feature representations. Specifically, our model includes two successive parts where two three-layer SAEs take image patches as input to learn the complex anatomical feature representation, and then these features are sent to Softmax classifier for inferring the labels. Experimental results validated the effectiveness of our method and showed that it outperformed four other classical brain tissue detection strategies. Furthermore, we reconstructed three-dimensional surfaces of these tissues, which show their potential in exploring the high-resolution anatomical structures of human brain. PMID:27057543

Segmenting Brain Tissues from Chinese Visible Human Dataset by Deep-Learned Features with Stacked Autoencoder.

PubMed

Zhao, Guangjun; Wang, Xuchu; Niu, Yanmin; Tan, Liwen; Zhang, Shao-Xiang

2016-01-01

Cryosection brain images in Chinese Visible Human (CVH) dataset contain rich anatomical structure information of tissues because of its high resolution (e.g., 0.167 mm per pixel). Fast and accurate segmentation of these images into white matter, gray matter, and cerebrospinal fluid plays a critical role in analyzing and measuring the anatomical structures of human brain. However, most existing automated segmentation methods are designed for computed tomography or magnetic resonance imaging data, and they may not be applicable for cryosection images due to the imaging difference. In this paper, we propose a supervised learning-based CVH brain tissues segmentation method that uses stacked autoencoder (SAE) to automatically learn the deep feature representations. Specifically, our model includes two successive parts where two three-layer SAEs take image patches as input to learn the complex anatomical feature representation, and then these features are sent to Softmax classifier for inferring the labels. Experimental results validated the effectiveness of our method and showed that it outperformed four other classical brain tissue detection strategies. Furthermore, we reconstructed three-dimensional surfaces of these tissues, which show their potential in exploring the high-resolution anatomical structures of human brain.

Portable wireless electrocorticography system with a flexible microelectrodes array for epilepsy treatment.

PubMed

Xie, Kejun; Zhang, Shaomin; Dong, Shurong; Li, Shijian; Yu, Chaonan; Xu, Kedi; Chen, Wanke; Guo, Wei; Luo, Jikui; Wu, Zhaohui

2017-08-10

In this paper, we present a portable wireless electrocorticography (ECoG) system. It uses a high resolution 32-channel flexible ECoG electrodes array to collect electrical signals of brain activities and to stimulate the lesions. Electronic circuits are designed for signal acquisition, processing and transmission using Bluetooth Low Energy 4 (LTE4) for wireless communication with cell phone. In-vivo experiments on a rat show that the flexible ECoG system can accurately record electrical signals of brain activities and transmit them to cell phone with a maximal sampling rate of 30 ksampling/s per channel. It demonstrates that the epilepsy lesions can be detected, located and treated through the ECoG system. The wireless ECoG system has low energy consumption and high brain spatial resolution, thus has great prospects for future application.

Rapid brain MRI acquisition techniques at ultra-high fields

PubMed Central

Setsompop, Kawin; Feinberg, David A.; Polimeni, Jonathan R.

2017-01-01

Ultra-high-field MRI provides large increases in signal-to-noise ratio as well as enhancement of several contrast mechanisms in both structural and functional imaging. Combined, these gains result in a substantial boost in contrast-to-noise ratio that can be exploited for higher spatial resolution imaging to extract finer-scale information about the brain. With increased spatial resolution, however, is a concurrent increased image encoding burden that can cause unacceptably long scan times for structural imaging and slow temporal sampling of the hemodynamic response in functional MRI—particularly when whole-brain imaging is desired. To address this issue, new directions of imaging technology development—such as the move from conventional 2D slice-by-slice imaging to more efficient Simultaneous MultiSlice (SMS) or MultiBand imaging (which can be viewed as “pseudo-3D” encoding) as well as full 3D imaging—have provided dramatic improvements in acquisition speed. Such imaging paradigms provide higher SNR efficiency as well as improved encoding efficiency. Moreover, SMS and 3D imaging can make better use of coil sensitivity information in multi-channel receiver arrays used for parallel imaging acquisitions through controlled aliasing in multiple spatial directions. This has enabled unprecedented acceleration factors of an order of magnitude or higher in these imaging acquisition schemes, with low image artifact levels and high SNR. Here we review the latest developments of SMS and 3D imaging methods and related technologies at ultra-high field for rapid high-resolution functional and structural imaging of the brain. PMID:26835884

Dual-slit confocal light sheet microscopy for in vivo whole-brain imaging of zebrafish

PubMed Central

Yang, Zhe; Mei, Li; Xia, Fei; Luo, Qingming; Fu, Ling; Gong, Hui

2015-01-01

In vivo functional imaging at single-neuron resolution is an important approach to visualize biological processes in neuroscience. Light sheet microscopy (LSM) is a cutting edge in vivo imaging technique that provides micron-scale spatial resolution at high frame rate. Due to the scattering and absorption of tissue, however, conventional LSM is inadequate to resolve cells because of the attenuated signal to noise ratio (SNR). Using dual-beam illumination and confocal dual-slit detection, here a dual-slit confocal LSM is demonstrated to obtain the SNR enhanced images with frame rate twice as high as line confocal LSM method. Through theoretical calculations and experiments, the correlation between the slit’s width and SNR was determined to optimize the image quality. In vivo whole brain structural imaging stacks and the functional imaging sequences of single slice were obtained for analysis of calcium activities at single-cell resolution. A two-fold increase in imaging speed of conventional confocal LSM makes it possible to capture the sequence of the neurons’ activities and help reveal the potential functional connections in the whole zebrafish’s brain. PMID:26137381

Towards Ultra-High Resolution Fibre Tract Mapping of the Human Brain – Registration of Polarised Light Images and Reorientation of Fibre Vectors

PubMed Central

Palm, Christoph; Axer, Markus; Gräßel, David; Dammers, Jürgen; Lindemeyer, Johannes; Zilles, Karl; Pietrzyk, Uwe; Amunts, Katrin

2009-01-01

Polarised light imaging (PLI) utilises the birefringence of the myelin sheaths in order to visualise the orientation of nerve fibres in microtome sections of adult human post-mortem brains at ultra-high spatial resolution. The preparation of post-mortem brains for PLI involves fixation, freezing and cutting into 100-μm-thick sections. Hence, geometrical distortions of histological sections are inevitable and have to be removed for 3D reconstruction and subsequent fibre tracking. We here present a processing pipeline for 3D reconstruction of these sections using PLI derived multimodal images of post-mortem brains. Blockface images of the brains were obtained during cutting; they serve as reference data for alignment and elimination of distortion artefacts. In addition to the spatial image transformation, fibre orientation vectors were reoriented using the transformation fields, which consider both affine and subsequent non-linear registration. The application of this registration and reorientation approach results in a smooth fibre vector field, which reflects brain morphology. PLI combined with 3D reconstruction and fibre tracking is a powerful tool for human brain mapping. It can also serve as an independent method for evaluating in vivo fibre tractography. PMID:20461231

Highest Resolution In Vivo Human Brain MRI Using Prospective Motion Correction

PubMed Central

Stucht, Daniel; Danishad, K. Appu; Schulze, Peter; Godenschweger, Frank; Zaitsev, Maxim; Speck, Oliver

2015-01-01

High field MRI systems, such as 7 Tesla (T) scanners, can deliver higher signal to noise ratio (SNR) than lower field scanners and thus allow for the acquisition of data with higher spatial resolution, which is often demanded by users in the fields of clinical and neuroscientific imaging. However, high resolution scans may require long acquisition times, which in turn increase the discomfort for the subject and the risk of subject motion. Even with a cooperative and trained subject, involuntary motion due to heartbeat, swallowing, respiration and changes in muscle tone can cause image artifacts that reduce the effective resolution. In addition, scanning with higher resolution leads to increased sensitivity to even very small movements. Prospective motion correction (PMC) at 3T and 7T has proven to increase image quality in case of subject motion. Although the application of prospective motion correction is becoming more popular, previous articles focused on proof of concept studies and technical descriptions, whereas this paper briefly describes the technical aspects of the optical tracking system, marker fixation and cross calibration and focuses on the application of PMC to very high resolution imaging without intentional motion. In this study we acquired in vivo MR images at 7T using prospective motion correction during long acquisitions. As a result, we present images among the highest, if not the highest resolution of in vivo human brain MRI ever acquired. PMID:26226146

Convergence and divergence across construction methods for human brain white matter networks: an assessment based on individual differences.

PubMed

Zhong, Suyu; He, Yong; Gong, Gaolang

2015-05-01

Using diffusion MRI, a number of studies have investigated the properties of whole-brain white matter (WM) networks with differing network construction methods (node/edge definition). However, how the construction methods affect individual differences of WM networks and, particularly, if distinct methods can provide convergent or divergent patterns of individual differences remain largely unknown. Here, we applied 10 frequently used methods to construct whole-brain WM networks in a healthy young adult population (57 subjects), which involves two node definitions (low-resolution and high-resolution) and five edge definitions (binary, FA weighted, fiber-density weighted, length-corrected fiber-density weighted, and connectivity-probability weighted). For these WM networks, individual differences were systematically analyzed in three network aspects: (1) a spatial pattern of WM connections, (2) a spatial pattern of nodal efficiency, and (3) network global and local efficiencies. Intriguingly, we found that some of the network construction methods converged in terms of individual difference patterns, but diverged with other methods. Furthermore, the convergence/divergence between methods differed among network properties that were adopted to assess individual differences. Particularly, high-resolution WM networks with differing edge definitions showed convergent individual differences in the spatial pattern of both WM connections and nodal efficiency. For the network global and local efficiencies, low-resolution and high-resolution WM networks for most edge definitions consistently exhibited a highly convergent pattern in individual differences. Finally, the test-retest analysis revealed a decent temporal reproducibility for the patterns of between-method convergence/divergence. Together, the results of the present study demonstrated a measure-dependent effect of network construction methods on the individual difference of WM network properties. © 2015 Wiley Periodicals, Inc.

Design analysis of an MPI human functional brain scanner

PubMed Central

Mason, Erica E.; Cooley, Clarissa Z.; Cauley, Stephen F.; Griswold, Mark A.; Conolly, Steven M.; Wald, Lawrence L.

2017-01-01

MPI’s high sensitivity makes it a promising modality for imaging brain function. Functional contrast is proposed based on blood SPION concentration changes due to Cerebral Blood Volume (CBV) increases during activation, a mechanism utilized in fMRI studies. MPI offers the potential for a direct and more sensitive measure of SPION concentration, and thus CBV, than fMRI. As such, fMPI could surpass fMRI in sensitivity, enhancing the scientific and clinical value of functional imaging. As human-sized MPI systems have not been attempted, we assess the technical challenges of scaling MPI from rodent to human brain. We use a full-system MPI simulator to test arbitrary hardware designs and encoding practices, and we examine tradeoffs imposed by constraints that arise when scaling to human size as well as safety constraints (PNS and central nervous system stimulation) not considered in animal scanners, thereby estimating spatial resolutions and sensitivities achievable with current technology. Using a projection FFL MPI system, we examine coil hardware options and their implications for sensitivity and spatial resolution. We estimate that an fMPI brain scanner is feasible, although with reduced sensitivity (20×) and spatial resolution (5×) compared to existing rodent systems. Nonetheless, it retains sufficient sensitivity and spatial resolution to make it an attractive future instrument for studying the human brain; additional technical innovations can result in further improvements. PMID:28752130

Characterization of dynamic changes of current source localization based on spatiotemporal fMRI constrained EEG source imaging

NASA Astrophysics Data System (ADS)

Nguyen, Thinh; Potter, Thomas; Grossman, Robert; Zhang, Yingchun

2018-06-01

Objective. Neuroimaging has been employed as a promising approach to advance our understanding of brain networks in both basic and clinical neuroscience. Electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) represent two neuroimaging modalities with complementary features; EEG has high temporal resolution and low spatial resolution while fMRI has high spatial resolution and low temporal resolution. Multimodal EEG inverse methods have attempted to capitalize on these properties but have been subjected to localization error. The dynamic brain transition network (DBTN) approach, a spatiotemporal fMRI constrained EEG source imaging method, has recently been developed to address these issues by solving the EEG inverse problem in a Bayesian framework, utilizing fMRI priors in a spatial and temporal variant manner. This paper presents a computer simulation study to provide a detailed characterization of the spatial and temporal accuracy of the DBTN method. Approach. Synthetic EEG data were generated in a series of computer simulations, designed to represent realistic and complex brain activity at superficial and deep sources with highly dynamical activity time-courses. The source reconstruction performance of the DBTN method was tested against the fMRI-constrained minimum norm estimates algorithm (fMRIMNE). The performances of the two inverse methods were evaluated both in terms of spatial and temporal accuracy. Main results. In comparison with the commonly used fMRIMNE method, results showed that the DBTN method produces results with increased spatial and temporal accuracy. The DBTN method also demonstrated the capability to reduce crosstalk in the reconstructed cortical time-course(s) induced by neighboring regions, mitigate depth bias and improve overall localization accuracy. Significance. The improved spatiotemporal accuracy of the reconstruction allows for an improved characterization of complex neural activity. This improvement can be extended to any subsequent brain connectivity analyses used to construct the associated dynamic brain networks.

Sex Differences in Brain Volume Are Related to Specific Skills, Not to General Intelligence

ERIC Educational Resources Information Center

Burgaleta, Miguel; Head, Kevin; Alvarez-Linera, Juan; Martinez, Kenia; Escorial, Sergio; Haier, Richard; Colom, Roberto

2012-01-01

It has been proposed that males would show higher mean scores than females in general intelligence ("g") because (1) men have, on average, larger brains than women, and (2) brain volume correlates with "g." Here we report a failure to support the conclusion derived from these premises. High resolution MRIs were acquired in a sample of one hundred…

Pilot Study on Long Term Effects of HZE Exposure on the Canine Brain

NASA Astrophysics Data System (ADS)

Budinger, T.; Brennan, K.; Pearlstein, R.

A ground-based pilot experiment was initiated in December 1992 to evaluate the long term effects on health and aging after HZE cosmic radiation of the canine brain. Six adult male beagle dogs (1 yr) from the UC Davis breeding colony at the Laboratory for Energy Related Health Research were researched in this study. Iron nuclei at 600 MeV/amu (180 keV/mm) were used to irradiate the whole brain. The fluence of 3 x 106 iron nuclei/ cm2 mimics the HZE exposure (all > He) for a 2- year mission to Mars. The HZE irradiation was a fully stripped iron particle beam at the LBNL BEVALAC. Using a Raster Scanner we were able to spread the beam to deliver a uniform dose over the brain. The total dose to the brain was 200 cGy. Four dogs were whole brain irradiated with iron and two dogs served as litter-mate controls. The control dogs received a similar amount of background neutron irradiation as the irradiated dogs. One of the control dogs died suddenly 3/98 of intestinal cancer unrelated to the brain irradiation. That brain was not harvested before autolysis had prevented analysis. Periodic PET metabolism and yearly MRI studies have been done on these dog's brain since irradiation. All dogs had yearly physical, neurological and blood chemistry work-ups. PET imaging was performed with the Donner 600-crystal high-resolution PET (2.6 mm resolution) and with the commercial PET, CTI/Siemens ECAT 951 PET Scanner (5 mm resolution). NMR imaging is performed with the 1 5T GE Signa at UCSF using T spoiled gradient imaging.1 sequences for T1 contrast at 1 mm resolution as well as a T2 weighted spin echo imaging sequence at 1 mm resolution. A major goal of this work is to present an accurate method for measuring surface areas and volumes of the irradiated vs the non-irradiated canine brain using MRI data which are isotropic in resolution at the 1 mm level. This allows us to monitor the changes in brain size with aging and radiation exposure. Nine years post irradiation, these dog brains (+ 3 additional age-matched controls) were in-situ perfused with 4% paraformaldehyde/01.M phosphate buffer. The brain was removed and fixed in the same fixative for 2 weeks. Brain sections were embedded in parafin and cut at 6 or 12 μm thickness. Histology included H&E, Luxol fast blue and Silver staining. Immunochemistry included Amyloidprecursor protein. There was no marked increase in amyloid plaque formation in the irradiated dogs. Imaging and histology results will be presented at the COSPAR conference.

Ultra high resolution imaging of the human head at 8 tesla: 2K x 2K for Y2K.

PubMed

Robitaille, P M; Abduljalil, A M; Kangarlu, A

2000-01-01

To acquire ultra high resolution MRI images of the human brain at 8 Tesla within a clinically acceptable time frame. Gradient echo images were acquired from the human head of normal subjects using a transverse electromagnetic resonator operating in quadrature and tuned to 340 MHz. In each study, a group of six images was obtained containing a total of 208 MB of unprocessed information. Typical acquisition parameters were as follows: matrix = 2,000 x 2,000, field of view = 20 cm, slice thickness = 2 mm, number of excitations (NEX) = 1, flip angle = 45 degrees, TR = 750 ms, TE = 17 ms, receiver bandwidth = 69.4 kHz. This resulted in a total scan time of 23 minutes, an in-plane resolution of 100 microm, and a pixel volume of 0.02 mm3. The ultra high resolution images acquired in this study represent more than a 50-fold increase in in-plane resolution relative to conventional 256 x 256 images obtained with a 20 cm field of view and a 5 mm slice thickness. Nonetheless, the ultra high resolution images could be acquired both with adequate image quality and signal to noise. They revealed numerous small venous structures throughout the image plane and provided reasonable delineation between gray and white matter. The elevated signal-to-noise ratio observed in ultra high field magnetic resonance imaging can be utilized to acquire images with a level of resolution approaching the histological level under in vivo conditions. However, brain motion is likely to degrade the useful resolution. This situation may be remedied in part with cardiac gating. Nonetheless, these images represent a significant advance in our ability to examine small anatomical features with noninvasive imaging methods.

3.0-T functional brain imaging: a 5-year experience.

PubMed

Scarabino, T; Giannatempo, G M; Popolizio, T; Tosetti, M; d'Alesio, V; Esposito, F; Di Salle, F; Di Costanzo, A; Bertolino, A; Maggialetti, A; Salvolini, U

2007-02-01

The aim of this paper is to illustrate the technical, methodological and diagnostic features of functional imaging (comprising spectroscopy, diffusion, perfusion and cortical activation techniques) and its principal neuroradiological applications on the basis of the experience gained by the authors in the 5 years since the installation of a high-field magnetic resonance (MR) magnet. These MR techniques are particularly effective at 3.0 Tesla (T) owing to their high signal, resolution and sensitivity, reduced scanning times and overall improved diagnostic ability. In particular, the high-field strength enhances spectroscopic analysis due to a greater signal-to-noise ratio (SNR) and improved spectral, space and time resolution, resulting in the ability to obtain high-resolution spectroscopic studies not only of the more common metabolites, but also--and especially--of those which, due to their smaller concentrations, are difficult to detect using 1.5-T systems. All of these advantages can be obtained with reduced acquisition times. In diffusion studies, the high-field strength results in greater SNR, because 3.0-T magnets enable increased spatial resolution, which enhances accuracy. They also allow exploration in greater detail of more complex phenomena (such as diffusion tensor and tractography), which are not clearly depicted on 1.5-T systems. The most common perfusion study (with intravenous injection of a contrast agent) benefits from the greater SNR and higher magnetic susceptibility by achieving dramatically improved signal changes, and thus greater reliability, using smaller doses of contrast agent. Functional MR imaging (fMRI) is without doubt the modality in which high-field strength has had the greatest impact. Images acquired with the blood-oxygen-level-dependent (BOLD) technique benefit from the greater SNR afforded by 3.0-T magnets and from their stronger magnetic susceptibility effects, providing higher signal and spatial resolution. This enhances reliability of the localisation of brain functions, making it possible to map additional areas, even in the millimetre and submillimetre scale. The data presented and results obtained to date show that 3.0-T morphofunctional imaging can become the standard for high-resolution investigation of brain disease.

Two-photon imaging in living brain slices.

PubMed

Mainen, Z F; Maletic-Savatic, M; Shi, S H; Hayashi, Y; Malinow, R; Svoboda, K

1999-06-01

Two-photon excitation laser scanning microscopy (TPLSM) has become the tool of choice for high-resolution fluorescence imaging in intact neural tissues. Compared with other optical techniques, TPLSM allows high-resolution imaging and efficient detection of fluorescence signal with minimal photobleaching and phototoxicity. The advantages of TPLSM are especially pronounced in highly scattering environments such as the brain slice. Here we describe our approaches to imaging various aspects of synaptic function in living brain slices. To combine several imaging modes together with patch-clamp electrophysiological recordings we found it advantageous to custom-build an upright microscope. Our design goals were primarily experimental convenience and efficient collection of fluorescence. We describe our TPLSM imaging system and its performance in detail. We present dynamic measurements of neuronal morphology of neurons expressing green fluorescent protein (GFP) and GFP fusion proteins as well as functional imaging of calcium dynamics in individual dendritic spines. Although our microscope is a custom instrument, its key advantages can be easily implemented as a modification of commercial laser scanning microscopes. Copyright 1999 Academic Press.

Single-cell imaging tools for brain energy metabolism: a review

PubMed Central

San Martín, Alejandro; Sotelo-Hitschfeld, Tamara; Lerchundi, Rodrigo; Fernández-Moncada, Ignacio; Ceballo, Sebastian; Valdebenito, Rocío; Baeza-Lehnert, Felipe; Alegría, Karin; Contreras-Baeza, Yasna; Garrido-Gerter, Pamela; Romero-Gómez, Ignacio; Barros, L. Felipe

2014-01-01

Abstract. Neurophotonics comes to light at a time in which advances in microscopy and improved calcium reporters are paving the way toward high-resolution functional mapping of the brain. This review relates to a parallel revolution in metabolism. We argue that metabolism needs to be approached both in vitro and in vivo, and that it does not just exist as a low-level platform but is also a relevant player in information processing. In recent years, genetically encoded fluorescent nanosensors have been introduced to measure glucose, glutamate, ATP, NADH, lactate, and pyruvate in mammalian cells. Reporting relative metabolite levels, absolute concentrations, and metabolic fluxes, these sensors are instrumental for the discovery of new molecular mechanisms. Sensors continue to be developed, which together with a continued improvement in protein expression strategies and new imaging technologies, herald an exciting era of high-resolution characterization of metabolism in the brain and other organs. PMID:26157964

A three-dimensional stereotaxic MRI brain atlas of the cichlid fish Oreochromis mossambicus.

PubMed

Simões, José M; Teles, Magda C; Oliveira, Rui F; Van der Linden, Annemie; Verhoye, Marleen

2012-01-01

The African cichlid Oreochromis mossambicus (Mozambique tilapia) has been used as a model system in a wide range of behavioural and neurobiological studies. The increasing number of genetic tools available for this species, together with the emerging interest in its use for neurobiological studies, increased the need for an accurate hodological mapping of the tilapia brain to supplement the available histological data. The goal of our study was to elaborate a three-dimensional, high-resolution digital atlas using magnetic resonance imaging, supported by Nissl staining. Resulting images were viewed and analysed in all orientations (transverse, sagittal, and horizontal) and manually labelled to reveal structures in the olfactory bulb, telencephalon, diencephalon, optic tectum, and cerebellum. This high resolution tilapia brain atlas is expected to become a very useful tool for neuroscientists using this fish model and will certainly expand their use in future studies regarding the central nervous system.

Fiber optic in vivo imaging in the mammalian nervous system

PubMed Central

Mehta, Amit D; Jung, Juergen C; Flusberg, Benjamin A; Schnitzer, Mark J

2010-01-01

The compact size, mechanical flexibility, and growing functionality of optical fiber and fiber optic devices are enabling several new modalities for imaging the mammalian nervous system in vivo. Fluorescence microendoscopy is a minimally invasive fiber modality that provides cellular resolution in deep brain areas. Diffuse optical tomography is a non-invasive modality that uses assemblies of fiber optic emitters and detectors on the cranium for volumetric imaging of brain activation. Optical coherence tomography is a sensitive interferometric imaging technique that can be implemented in a variety of fiber based formats and that might allow intrinsic optical detection of brain activity at a high resolution. Miniaturized fiber optic microscopy permits cellular level imaging in the brains of behaving animals. Together, these modalities will enable new uses of imaging in the intact nervous system for both research and clinical applications. PMID:15464896

Patch-Based Super-Resolution of MR Spectroscopic Images: Application to Multiple Sclerosis

PubMed Central

Jain, Saurabh; Sima, Diana M.; Sanaei Nezhad, Faezeh; Hangel, Gilbert; Bogner, Wolfgang; Williams, Stephen; Van Huffel, Sabine; Maes, Frederik; Smeets, Dirk

2017-01-01

Purpose: Magnetic resonance spectroscopic imaging (MRSI) provides complementary information to conventional magnetic resonance imaging. Acquiring high resolution MRSI is time consuming and requires complex reconstruction techniques. Methods: In this paper, a patch-based super-resolution method is presented to increase the spatial resolution of metabolite maps computed from MRSI. The proposed method uses high resolution anatomical MR images (T1-weighted and Fluid-attenuated inversion recovery) to regularize the super-resolution process. The accuracy of the method is validated against conventional interpolation techniques using a phantom, as well as simulated and in vivo acquired human brain images of multiple sclerosis subjects. Results: The method preserves tissue contrast and structural information, and matches well with the trend of acquired high resolution MRSI. Conclusions: These results suggest that the method has potential for clinically relevant neuroimaging applications. PMID:28197066

Prediction of brain maturity based on cortical thickness at different spatial resolutions.

PubMed

Khundrakpam, Budhachandra S; Tohka, Jussi; Evans, Alan C

2015-05-01

Several studies using magnetic resonance imaging (MRI) scans have shown developmental trajectories of cortical thickness. Cognitive milestones happen concurrently with these structural changes, and a delay in such changes has been implicated in developmental disorders such as attention-deficit/hyperactivity disorder (ADHD). Accurate estimation of individuals' brain maturity, therefore, is critical in establishing a baseline for normal brain development against which neurodevelopmental disorders can be assessed. In this study, cortical thickness derived from structural magnetic resonance imaging (MRI) scans of a large longitudinal dataset of normally growing children and adolescents (n=308), were used to build a highly accurate predictive model for estimating chronological age (cross-validated correlation up to R=0.84). Unlike previous studies which used kernelized approach in building prediction models, we used an elastic net penalized linear regression model capable of producing a spatially sparse, yet accurate predictive model of chronological age. Upon investigating different scales of cortical parcellation from 78 to 10,240 brain parcels, we observed that the accuracy in estimated age improved with increased spatial scale of brain parcellation, with the best estimations obtained for spatial resolutions consisting of 2560 and 10,240 brain parcels. The top predictors of brain maturity were found in highly localized sensorimotor and association areas. The results of our study demonstrate that cortical thickness can be used to estimate individuals' brain maturity with high accuracy, and the estimated ages relate to functional and behavioural measures, underscoring the relevance and scope of the study in the understanding of biological maturity. Copyright © 2015 Elsevier Inc. All rights reserved.

AP-MALDI Mass Spectrometry Imaging of Gangliosides Using 2,6-Dihydroxyacetophenone

NASA Astrophysics Data System (ADS)

Jackson, Shelley N.; Muller, Ludovic; Roux, Aurelie; Oktem, Berk; Moskovets, Eugene; Doroshenko, Vladimir M.; Woods, Amina S.

2018-03-01

Matrix-assisted laser/desorption ionization (MALDI) mass spectrometry imaging (MSI) is widely used as a unique tool to record the distribution of a large range of biomolecules in tissues. 2,6-Dihydroxyacetophenone (DHA) matrix has been shown to provide efficient ionization of lipids, especially gangliosides. The major drawback for DHA as it applies to MS imaging is that it sublimes under vacuum (low pressure) at the extended time necessary to complete both high spatial and mass resolution MSI studies of whole organs. To overcome the problem of sublimation, we used an atmospheric pressure (AP)-MALDI source to obtain high spatial resolution images of lipids in the brain using a high mass resolution mass spectrometer. Additionally, the advantages of atmospheric pressure and DHA for imaging gangliosides are highlighted. The imaging of [M-H]- and [M-H2O-H]- mass peaks for GD1 gangliosides showed different distribution, most likely reflecting the different spatial distribution of GD1a and GD1b species in the brain. [Figure not available: see fulltext.

Submicron-resolution photoacoustic microscopy of endogenous light-absorbing biomolecules

NASA Astrophysics Data System (ADS)

Zhang, Chi

Photoacoustic imaging in biomedicine has the unique advantage of probing endogenous light absorbers at various length scales with a 100% relative sensitivity. Among the several modalities of photoacoustic imaging, optical-resolution photoacoustic microscopy (OR-PAM) can achieve high spatial resolution, on the order of optical wavelength, at <1 mm depth in biological tissue (the optical ballistic regime). OR-PAM has been applied successfully to structural and functional imaging of blood vasculature and red blood cells in vivo. Any molecules which absorb sufficient light at certain wavelengths can potentially be imaged by PAM. Compared with pure optical imaging, which typically targets fluorescent markers, label-free PAM avoids the major concerns that the fluorescent labeling probes may disturb the function of biomolecules and may have an insufficient density. This dissertation aims to advance label-free OR-PAM to the subcellular scale. The first part of this dissertation describes the technological advancement of PAM yielding high spatial resolution in 3D. The lateral resolution was improved by using optical objectives with high numerical apertures for optical focusing. The axial resolution was improved by using broadband ultrasonic transducers for ultrasound detection. We achieved 220 nm lateral resolution in transmission mode, 0.43 microm lateral resolution in reflection mode, 7.6 microm axial resolution in normal tissue, and 5.8 microm axial resolution with silicone oil immersion/injection. The achieved lateral resolution and axial resolution were the finest reported at the time. With high-resolution in 3D, PAM was demonstrated to resolve cellular and subcellular structures in vivo, such as red blood cells and melanosomes in melanoma cells. Compared with previous PAM systems, our high-resolution PAM could resolve capillaries in mouse ears more clearly. As an example application, we demonstrated intracellular temperature imaging, assisted by fluorescence signal detection, with sub-degree temperature resolution and sub-micron lateral resolution. The second part of this dissertation describes the exploration of endogenous light-absorbing biomolecules for PAM. We demonstrated cytochromes and myoglobin as new absorption contrasts for PAM and identified the corresponding optimal wavelengths for imaging. Fixed fibroblasts on slides and mouse ear sections were imaged by PAM at 422 nm and 250 nm wavelengths to reveal cytoplasms and nuclei, respectively, as confirmed by standard hematoxylin and eosin (H&E) histology. By imaging a blood-perfused mouse heart at 532 nm down to 150 microm in depth, we derived the myocardial sheet thickness and the cleavage height from an undehydrated heart for the first time. The findings promote PAM at new wavelengths and open up new possibilities for characterizing biological tissue. Of particular interest, dual-wavelength PAM around 250 nm and 420 nm wavelengths is analogous to H&E histology. The last part of this dissertation describes the development of sectioning photoacoustic microscopy (SPAM), based on the advancement in spatial resolution and new contrasts for PAM, with applications in brain histology. Label-free SPAM, assisted by a microtome, acquires serial distortion-free images of a specimen on the surface. By exciting cell nuclei at 266 nm wavelength with high resolution, SPAM could pinpoint cell nuclei sensitively and specifically in the mouse brain section, as confirmed by H&E histology. SPAM was demonstrated to generate high-resolution 3D images, highlighting cell nuclei, of formalin-fixed paraffin-embedded mouse brains without tissue staining or clearing. SPAM can potentially serve as a high-throughput and minimal-artifact substitute for histology, probe many other biomolecules and cells, and become a universal tool for animal or human whole-organ microscopy, with diverse applications in life sciences.

Hydrogel-Tissue Chemistry: Principles and Applications.

PubMed

Gradinaru, Viviana; Treweek, Jennifer; Overton, Kristin; Deisseroth, Karl

2018-05-20

Over the past five years, a rapidly developing experimental approach has enabled high-resolution and high-content information retrieval from intact multicellular animal (metazoan) systems. New chemical and physical forms are created in the hydrogel-tissue chemistry process, and the retention and retrieval of crucial phenotypic information regarding constituent cells and molecules (and their joint interrelationships) are thereby enabled. For example, rich data sets defining both single-cell-resolution gene expression and single-cell-resolution activity during behavior can now be collected while still preserving information on three-dimensional positioning and/or brain-wide wiring of those very same neurons-even within vertebrate brains. This new approach and its variants, as applied to neuroscience, are beginning to illuminate the fundamental cellular and chemical representations of sensation, cognition, and action. More generally, reimagining metazoans as metareactants-or positionally defined three-dimensional graphs of constituent chemicals made available for ongoing functionalization, transformation, and readout-is stimulating innovation across biology and medicine.

Rapid simultaneous high-resolution mapping of myelin water fraction and relaxation times in human brain using BMC-mcDESPOT.

PubMed

Bouhrara, Mustapha; Spencer, Richard G

2017-02-15

A number of central nervous system (CNS) diseases exhibit changes in myelin content and magnetic resonance longitudinal, T 1 , and transverse, T 2 , relaxation times, which therefore represent important biomarkers of CNS pathology. Among the methods applied for measurement of myelin water fraction (MWF) and relaxation times, the multicomponent driven equilibrium single pulse observation of T 1 and T 2 (mcDESPOT) approach is of particular interest. mcDESPOT permits whole brain mapping of multicomponent T 1 and T 2 , with data acquisition accomplished within a clinically realistic acquisition time. Unfortunately, previous studies have indicated the limited performance of mcDESPOT in the setting of the modest signal-to-noise range of high-resolution mapping, required for the depiction of small structures and to reduce partial volume effects. Recently, we showed that a new Bayesian Monte Carlo (BMC) analysis substantially improved determination of MWF from mcDESPOT imaging data. However, our previous study was limited in that it did not discuss determination of relaxation times. Here, we extend the BMC analysis to the simultaneous determination of whole-brain MWF and relaxation times using the two-component mcDESPOT signal model. Simulation analyses and in-vivo human brain studies indicate the overall greater performance of this approach compared to the stochastic region contraction (SRC) algorithm, conventionally used to derive parameter estimates from mcDESPOT data. SRC estimates of the transverse relaxation time of the long T 2 fraction, T 2,l , and the longitudinal relaxation time of the short T 1 fraction, T 1,s , clustered towards the lower and upper parameter search space limits, respectively, indicating failure of the fitting procedure. We demonstrate that this effect is absent in the BMC analysis. Our results also showed improved parameter estimation for BMC as compared to SRC for high-resolution mapping. Overall we find that the combination of BMC analysis and mcDESPOT, BMC-mcDESPOT, shows excellent performance for accurate high-resolution whole-brain mapping of MWF and bi-component transverse and longitudinal relaxation times within a clinically realistic acquisition time. Published by Elsevier Inc.

Virtual Brain Bank a public collection of classified head MRI

NASA Astrophysics Data System (ADS)

Barrios, Fernando A.

2000-10-01

In this work I present the effort at the Neurobiology Center for creating a digital Brain Bank, a collection of well classified human brains that are used for teaching and research, this bank will be based in a collection of high resolution three dimensional head MRI. For this reason this bank is being named "virtual" and eventually will be of public access though a WEB page in the INTERNET.

In vivo functional connectome of human brainstem nuclei of the ascending arousal, autonomic, and motor systems by high spatial resolution 7-Tesla fMRI.

PubMed

Bianciardi, Marta; Toschi, Nicola; Eichner, Cornelius; Polimeni, Jonathan R; Setsompop, Kawin; Brown, Emery N; Hämäläinen, Matti S; Rosen, Bruce R; Wald, Lawrence L

2016-06-01

Our aim was to map the in vivo human functional connectivity of several brainstem nuclei with the rest of the brain by using seed-based correlation of ultra-high magnetic field functional magnetic resonance imaging (fMRI) data. We used the recently developed template of 11 brainstem nuclei derived from multi-contrast structural MRI at 7 Tesla as seed regions to determine their connectivity to the rest of the brain. To achieve this, we used the increased contrast-to-noise ratio of 7-Tesla fMRI compared with 3 Tesla and time-efficient simultaneous multi-slice imaging to cover the brain with high spatial resolution (1.1-mm isotropic nominal resolution) while maintaining a short repetition time (2.5 s). The delineated Pearson's correlation-based functional connectivity diagrams (connectomes) of 11 brainstem nuclei of the ascending arousal, motor, and autonomic systems from 12 controls are presented and discussed in the context of existing histology and animal work. Considering that the investigated brainstem nuclei play a crucial role in several vital functions, the delineated preliminary connectomes might prove useful for future in vivo research and clinical studies of human brainstem function and pathology, including disorders of consciousness, sleep disorders, autonomic disorders, Parkinson's disease, and other motor disorders.

Postmortem diffusion MRI of the human brainstem and thalamus for deep brain stimulator electrode localization

PubMed Central

Calabrese, Evan; Hickey, Patrick; Hulette, Christine; Zhang, Jingxian; Parente, Beth; Lad, Shivanand P.; Johnson, G. Allan

2015-01-01

Deep brain stimulation (DBS) is an established surgical therapy for medically refractory tremor disorders including essential tremor (ET) and is currently under investigation for use in a variety of other neurologic and psychiatric disorders. There is growing evidence that the anti-tremor effects of DBS for ET are directly related to modulation of the dentatorubrothalamic tract (DRT), a white matter pathway that connects the cerebellum, red nucleus, and ventral intermediate nucleus of the thalamus. Emerging white matter targets for DBS, like the DRT, will require improved 3D reference maps of deep brain anatomy and structural connectivity for accurate electrode targeting. High-resolution diffusion MRI of postmortem brain specimens can provide detailed volumetric images of important deep brain nuclei and 3D reconstructions of white matter pathways with probabilistic tractography techniques. We present a high spatial and angular resolution diffusion MRI template of the postmortem human brainstem and thalamus with 3D reconstructions of the nuclei and white matter tracts involved in ET circuitry. We demonstrate accurate registration of these data to in vivo, clinical images from patients receiving DBS therapy, and correlate electrode proximity to tractography of the DRT with improvement of ET symptoms. PMID:26043869

Revealing the cerebello-ponto-hypothalamic pathway in the human brain.

PubMed

Kamali, Arash; Karbasian, Niloofar; Rabiei, Pejman; Cano, Andres; Riascos, Roy F; Tandon, Nitin; Arevalo, Octavio; Ocasio, Laura; Younes, Kyan; Khayat-Khoei, Mahsa; Mirbagheri, Saeedeh; Hasan, Khader M

2018-06-11

The cerebellum is shown to be involved in some limbic functions of the human brain such as emotion and affect. The major connection of the cerebellum with the limbic system is known to be through the cerebello-hypothalamic pathways. The consensus is that the projections from the cerebellar nuclei to the limbic system, and particularly the hypothalamus, or from the hypothalamus to the cerebellar nuclei, are through multisynaptic pathways in the bulbar reticular formation. The detailed anatomy of the pathways responsible for mediating these responses, however, is yet to be determined. Diffusion tensor imaging may be helpful in better visualizing the surgical anatomy of the cerebello-ponto-hypothalamic (CPH) pathway. This study aimed to investigate the utility of high-spatial-resolution diffusion tensor tractography for mapping the trajectory of the CPH tract in the human brain. Fifteen healthy adults were studied. We delineated, for the first time, the detailed trajectory of the CPH tract of the human brain in fifteen normal adult subjects using high-spatial-resolution diffusion tensor tractography. We further revealed the close relationship of the CPH tract with the optic tract, temporo-pontine tract, amygdalofugal tract and the fornix in the human brain. Copyright © 2018 Elsevier B.V. All rights reserved.

Frequency analysis of the visual steady-state response measured with the fast optical signal in younger and older adults.

PubMed

Tse, Chun-Yu; Gordon, Brian A; Fabiani, Monica; Gratton, Gabriele

2010-09-01

Relatively high frequency activity (>4Hz) carries important information about the state of the brain or its response to high frequency events. The electroencephalogram (EEG) is commonly used to study these changes because it possesses high temporal resolution and a good signal-to-noise ratio. However, it provides limited spatial information. Non-invasive fast optical signals (FOS) have been proposed as a neuroimaging tool combining spatial and temporal resolution. Yet, this technique has not been applied to study high frequency brain oscillations because of its relatively low signal-to-noise ratio. Here we investigate the sensitivity of FOS to relatively high-frequency brain oscillations. We measured the steady-state optical response elicited in medial and lateral occipital cortex by checkerboard reversals occurring at 4, 6, and 8Hz in younger and older adults. Stimulus-dependent oscillations were observed at the predicted stimulation frequency. In addition, in the younger adults the FOS steady-state response was smaller in lateral than medial areas, whereas in the older adults it was reversed in these two cortical regions. This may reflect diminished top-down inhibitory control in the older adults. The results indicate that FOS can be used to study the modulation of relatively high-frequency brain oscillations in adjacent cortical regions. Copyright (c) 2010 Elsevier B.V. All rights reserved.

Separate effects of sex hormones and sex chromosomes on brain structure and function revealed by high-resolution magnetic resonance imaging and spatial navigation assessment of the Four Core Genotype mouse model.

PubMed

Corre, Christina; Friedel, Miriam; Vousden, Dulcie A; Metcalf, Ariane; Spring, Shoshana; Qiu, Lily R; Lerch, Jason P; Palmert, Mark R

2016-03-01

Males and females exhibit several differences in brain structure and function. To examine the basis for these sex differences, we investigated the influences of sex hormones and sex chromosomes on brain structure and function in mice. We used the Four Core Genotype (4CG) mice, which can generate both male and female mice with XX or XY sex chromosome complement, allowing the decoupling of sex chromosomes from hormonal milieu. To examine whole brain structure, high-resolution ex vivo MRI was performed, and to assess differences in cognitive function, mice were trained on a radial arm maze. Voxel-wise and volumetric analyses of MRI data uncovered a striking independence of hormonal versus chromosomal influences in 30 sexually dimorphic brain regions. For example, the bed nucleus of the stria terminalis and the parieto-temporal lobe of the cerebral cortex displayed steroid-dependence while the cerebellar cortex, corpus callosum, and olfactory bulbs were influenced by sex chromosomes. Spatial learning and memory demonstrated strict hormone-dependency with no apparent influence of sex chromosomes. Understanding the influences of chromosomes and hormones on brain structure and function is important for understanding sex differences in brain structure and function, an endeavor that has eventual implications for understanding sex biases observed in the prevalence of psychiatric disorders.

Performance evaluation of a high-resolution brain PET scanner using four-layer MPPC DOI detectors.

PubMed

Watanabe, Mitsuo; Saito, Akinori; Isobe, Takashi; Ote, Kibo; Yamada, Ryoko; Moriya, Takahiro; Omura, Tomohide

2017-08-18

A high-resolution positron emission tomography (PET) scanner, dedicated to brain studies, was developed and its performance was evaluated. A four-layer depth of interaction detector was designed containing five detector units axially lined up per layer board. Each of the detector units consists of a finely segmented (1.2 mm) LYSO scintillator array and an 8  ×  8 array of multi-pixel photon counters. Each detector layer has independent front-end and signal processing circuits, and the four detector layers are assembled as a detector module. The new scanner was designed to form a detector ring of 430 mm diameter with 32 detector modules and 168 detector rings with a 1.2 mm pitch. The total crystal number is 655 360. The transaxial and axial field of views (FOVs) are 330 mm in diameter and 201.6 mm, respectively, which are sufficient to measure a whole human brain. The single-event data generated at each detector module were transferred to the data acquisition servers through optical fiber cables. The single-event data from all detector modules were merged and processed to create coincidence event data in on-the-fly software in the data acquisition servers. For image reconstruction, the high-resolution mode (HR-mode) used a 1.2 mm 2 crystal segment size and the high-speed mode (HS-mode) used a 4.8 mm 2 size by collecting 16 crystal segments of 1.2 mm each to reduce the computational cost. The performance of the brain PET scanner was evaluated. For the intrinsic spatial resolution of the detector module, coincidence response functions of the detector module pair, which faced each other at various angles, were measured by scanning a 0.25 mm diameter 22 Na point source. The intrinsic resolutions were obtained with 1.08 mm full width at half-maximum (FWHM) and 1.25 mm FWHM on average at 0 and 22.5 degrees in the first layer pair, respectively. The system spatial resolutions were less than 1.0 mm FWHM throughout the whole FOV, using a list-mode dynamic RAMLA (LM-DRAMA). The system sensitivity was 21.4 cps kBq -1 as measured using an 18 F line source aligned with the center of the transaxial FOV. High count rate capability was evaluated using a cylindrical phantom (20 cm diameter  ×  70 cm length), resulting in 249 kcps in true and 27.9 kcps at 11.9 kBq ml -1 at the peak count in a noise equivalent count rate (NECR_2R). Single-event data acquisition and on-the-fly software coincidence detection performed well, exceeding 25 Mcps and 2.3 Mcps for single and coincidence count rates, respectively. Using phantom studies, we also demonstrated its imaging capabilities by means of a 3D Hoffman brain phantom and an ultra-micro hot-spot phantom. The images obtained were of acceptable quality for high-resolution determination. As clinical and pre-clinical studies, we imaged brains of a human and of small animals.

Performance evaluation of a high-resolution brain PET scanner using four-layer MPPC DOI detectors

NASA Astrophysics Data System (ADS)

Watanabe, Mitsuo; Saito, Akinori; Isobe, Takashi; Ote, Kibo; Yamada, Ryoko; Moriya, Takahiro; Omura, Tomohide

2017-09-01

A high-resolution positron emission tomography (PET) scanner, dedicated to brain studies, was developed and its performance was evaluated. A four-layer depth of interaction detector was designed containing five detector units axially lined up per layer board. Each of the detector units consists of a finely segmented (1.2 mm) LYSO scintillator array and an 8  ×  8 array of multi-pixel photon counters. Each detector layer has independent front-end and signal processing circuits, and the four detector layers are assembled as a detector module. The new scanner was designed to form a detector ring of 430 mm diameter with 32 detector modules and 168 detector rings with a 1.2 mm pitch. The total crystal number is 655 360. The transaxial and axial field of views (FOVs) are 330 mm in diameter and 201.6 mm, respectively, which are sufficient to measure a whole human brain. The single-event data generated at each detector module were transferred to the data acquisition servers through optical fiber cables. The single-event data from all detector modules were merged and processed to create coincidence event data in on-the-fly software in the data acquisition servers. For image reconstruction, the high-resolution mode (HR-mode) used a 1.2 mm2 crystal segment size and the high-speed mode (HS-mode) used a 4.8 mm2 size by collecting 16 crystal segments of 1.2 mm each to reduce the computational cost. The performance of the brain PET scanner was evaluated. For the intrinsic spatial resolution of the detector module, coincidence response functions of the detector module pair, which faced each other at various angles, were measured by scanning a 0.25 mm diameter 22Na point source. The intrinsic resolutions were obtained with 1.08 mm full width at half-maximum (FWHM) and 1.25 mm FWHM on average at 0 and 22.5 degrees in the first layer pair, respectively. The system spatial resolutions were less than 1.0 mm FWHM throughout the whole FOV, using a list-mode dynamic RAMLA (LM-DRAMA). The system sensitivity was 21.4 cps kBq-1 as measured using an 18F line source aligned with the center of the transaxial FOV. High count rate capability was evaluated using a cylindrical phantom (20 cm diameter  ×  70 cm length), resulting in 249 kcps in true and 27.9 kcps at 11.9 kBq ml-1 at the peak count in a noise equivalent count rate (NECR_2R). Single-event data acquisition and on-the-fly software coincidence detection performed well, exceeding 25 Mcps and 2.3 Mcps for single and coincidence count rates, respectively. Using phantom studies, we also demonstrated its imaging capabilities by means of a 3D Hoffman brain phantom and an ultra-micro hot-spot phantom. The images obtained were of acceptable quality for high-resolution determination. As clinical and pre-clinical studies, we imaged brains of a human and of small animals.

Microbleed and microinfarct detection in amyloid angiopathy: a high-resolution MRI-histopathology study

PubMed Central

van Veluw, Susanne J.; Charidimou, Andreas; van der Kouwe, Andre J.; Lauer, Arne; Reijmer, Yael D.; Costantino, Isabel; Gurol, M. Edip; Biessels, Geert Jan; Frosch, Matthew P.; Viswanathan, Anand; Greenberg, Steven M.

2016-01-01

Cerebral amyloid angiopathy is a common neuropathological finding in the ageing human brain, associated with cognitive impairment. Neuroimaging markers of severe cerebral amyloid angiopathy are cortical microbleeds and microinfarcts. These parenchymal brain lesions are considered key contributors to cognitive impairment. Therefore, they are important targets for therapeutic strategies and may serve as surrogate neuroimaging markers in clinical trials. We aimed to gain more insight into the pathological basis of magnetic resonance imaging-defined microbleeds and microinfarcts in cerebral amyloid angiopathy, and to explore the pathological burden that remains undetected, by using high and ultra-high resolution ex vivo magnetic resonance imaging, as well as detailed histological sampling. Brain samples from five cases (mean age 85 ± 6 years) with pathology-proven cerebral amyloid angiopathy and multiple microbleeds on in vivo clinical magnetic resonance imaging were subjected to high-resolution ex vivo 7 T magnetic resonance imaging. On the obtained high-resolution (200 μm isotropic voxels) ex vivo magnetic resonance images, 171 microbleeds were detected compared to 66 microbleeds on the corresponding in vivo magnetic resonance images. Of 13 sampled microbleeds that were matched on histology, five proved to be acute and eight old microhaemorrhages. The iron-positive old microhaemorrhages appeared approximately four times larger on magnetic resonance imaging compared to their size on histology. In addition, 48 microinfarcts were observed on ex vivo magnetic resonance imaging in three out of five cases (two cases exhibited no microinfarcts). None of them were visible on in vivo 1.5 T magnetic resonance imaging after a retrospective analysis. Of nine sampled microinfarcts that were matched on histology, five were confirmed as acute and four as old microinfarcts. Finally, we explored the proportion of microhaemorrhage and microinfarct burden that is beyond the detection limits of ex vivo magnetic resonance imaging, by scanning a smaller sample at ultra-high resolution, followed by serial sectioning. At ultra-high resolution (75 μm isotropic voxels) magnetic resonance imaging we observed an additional 48 microbleeds (compared to high resolution), which proved to correspond to vasculopathic changes (i.e. morphological changes to the small vessels) instead of frank haemorrhages on histology. After assessing the serial sections of this particular sample, no additional haemorrhages were observed that were missed on magnetic resonance imaging. In contrast, nine microinfarcts were found in these sections, of which six were only retrospectively visible at ultra-high resolution. In conclusion, these findings suggest that microbleeds on in vivo magnetic resonance imaging are specific for microhaemorrhages in cerebral amyloid angiopathy, and that increasing the resolution of magnetic resonance images results in the detection of more ‘non-haemorrhagic’ pathology. In contrast, the vast majority of microinfarcts currently remain under the detection limits of clinical in vivo magnetic resonance imaging. PMID:27645801

Warping an atlas derived from serial histology to 5 high-resolution MRIs.

PubMed

Tullo, Stephanie; Devenyi, Gabriel A; Patel, Raihaan; Park, Min Tae M; Collins, D Louis; Chakravarty, M Mallar

2018-06-19

Previous work from our group demonstrated the use of multiple input atlases to a modified multi-atlas framework (MAGeT-Brain) to improve subject-based segmentation accuracy. Currently, segmentation of the striatum, globus pallidus and thalamus are generated from a single high-resolution and -contrast MRI atlas derived from annotated serial histological sections. Here, we warp this atlas to five high-resolution MRI templates to create five de novo atlases. The overall goal of this work is to use these newly warped atlases as input to MAGeT-Brain in an effort to consolidate and improve the workflow presented in previous manuscripts from our group, allowing for simultaneous multi-structure segmentation. The work presented details the methodology used for the creation of the atlases using a technique previously proposed, where atlas labels are modified to mimic the intensity and contrast profile of MRI to facilitate atlas-to-template nonlinear transformation estimation. Dice's Kappa metric was used to demonstrate high quality registration and segmentation accuracy of the atlases. The final atlases are available at https://github.com/CobraLab/atlases/tree/master/5-atlas-subcortical.

Whole-brain high in-plane resolution fMRI using accelerated EPIK for enhanced characterisation of functional areas at 3T

PubMed Central

Yun, Seong Dae

2017-01-01

The relatively high imaging speed of EPI has led to its widespread use in dynamic MRI studies such as functional MRI. An approach to improve the performance of EPI, EPI with Keyhole (EPIK), has been previously presented and its use in fMRI was verified at 1.5T as well as 3T. The method has been proven to achieve a higher temporal resolution and smaller image distortions when compared to single-shot EPI. Furthermore, the performance of EPIK in the detection of functional signals was shown to be comparable to that of EPI. For these reasons, we were motivated to employ EPIK here for high-resolution imaging. The method was optimised to offer the highest possible in-plane resolution and slice coverage under the given imaging constraints: fixed TR/TE, FOV and acceleration factors for parallel imaging and partial Fourier techniques. The performance of EPIK was evaluated in direct comparison to the optimised protocol obtained from EPI. The two imaging methods were applied to visual fMRI experiments involving sixteen subjects. The results showed that enhanced spatial resolution with a whole-brain coverage was achieved by EPIK (1.00 mm × 1.00 mm; 32 slices) when compared to EPI (1.25 mm × 1.25 mm; 28 slices). As a consequence, enhanced characterisation of functional areas has been demonstrated in EPIK particularly for relatively small brain regions such as the lateral geniculate nucleus (LGN) and superior colliculus (SC); overall, a significantly increased t-value and activation area were observed from EPIK data. Lastly, the use of EPIK for fMRI was validated with the simulation of different types of data reconstruction methods. PMID:28945780

Regional differences in brain glucose metabolism determined by imaging mass spectrometry.

PubMed

Kleinridders, André; Ferris, Heather A; Reyzer, Michelle L; Rath, Michaela; Soto, Marion; Manier, M Lisa; Spraggins, Jeffrey; Yang, Zhihong; Stanton, Robert C; Caprioli, Richard M; Kahn, C Ronald

2018-06-01

Glucose is the major energy substrate of the brain and crucial for normal brain function. In diabetes, the brain is subject to episodes of hypo- and hyperglycemia resulting in acute outcomes ranging from confusion to seizures, while chronic metabolic dysregulation puts patients at increased risk for depression and Alzheimer's disease. In the present study, we aimed to determine how glucose is metabolized in different regions of the brain using imaging mass spectrometry (IMS). To examine the relative abundance of glucose and other metabolites in the brain, mouse brain sections were subjected to imaging mass spectrometry at a resolution of 100 μm. This was correlated with immunohistochemistry, qPCR, western blotting and enzyme assays of dissected brain regions to determine the relative contributions of the glycolytic and pentose phosphate pathways to regional glucose metabolism. In brain, there are significant regional differences in glucose metabolism, with low levels of hexose bisphosphate (a glycolytic intermediate) and high levels of the pentose phosphate pathway (PPP) enzyme glucose-6-phosphate dehydrogenase (G6PD) and PPP metabolite hexose phosphate in thalamus compared to cortex. The ratio of ATP to ADP is significantly higher in white matter tracts, such as corpus callosum, compared to less myelinated areas. While the brain is able to maintain normal ratios of hexose phosphate, hexose bisphosphate, ATP, and ADP during fasting, fasting causes a large increase in cortical and hippocampal lactate. These data demonstrate the importance of direct measurement of metabolic intermediates to determine regional differences in brain glucose metabolism and illustrate the strength of imaging mass spectrometry for investigating the impact of changing metabolic states on brain function at a regional level with high resolution. Copyright © 2018 The Authors. Published by Elsevier GmbH.. All rights reserved.

A rapid approach to high-resolution fluorescence imaging in semi-thick brain slices.

PubMed

Selever, Jennifer; Kong, Jian-Qiang; Arenkiel, Benjamin R

2011-07-26

A fundamental goal to both basic and clinical neuroscience is to better understand the identities, molecular makeup, and patterns of connectivity that are characteristic to neurons in both normal and diseased brain. Towards this, a great deal of effort has been placed on building high-resolution neuroanatomical maps(1-3). With the expansion of molecular genetics and advances in light microscopy has come the ability to query not only neuronal morphologies, but also the molecular and cellular makeup of individual neurons and their associated networks(4). Major advances in the ability to mark and manipulate neurons through transgenic and gene targeting technologies in the rodent now allow investigators to 'program' neuronal subsets at will(5-6). Arguably, one of the most influential contributions to contemporary neuroscience has been the discovery and cloning of genes encoding fluorescent proteins (FPs) in marine invertebrates(7-8), alongside their subsequent engineering to yield an ever-expanding toolbox of vital reporters(9). Exploiting cell type-specific promoter activity to drive targeted FP expression in discrete neuronal populations now affords neuroanatomical investigation with genetic precision. Engineering FP expression in neurons has vastly improved our understanding of brain structure and function. However, imaging individual neurons and their associated networks in deep brain tissues, or in three dimensions, has remained a challenge. Due to high lipid content, nervous tissue is rather opaque and exhibits auto fluorescence. These inherent biophysical properties make it difficult to visualize and image fluorescently labelled neurons at high resolution using standard epifluorescent or confocal microscopy beyond depths of tens of microns. To circumvent this challenge investigators often employ serial thin-section imaging and reconstruction methods(10), or 2-photon laser scanning microscopy(11). Current drawbacks to these approaches are the associated labor-intensive tissue preparation, or cost-prohibitive instrumentation respectively. Here, we present a relatively rapid and simple method to visualize fluorescently labelled cells in fixed semi-thick mouse brain slices by optical clearing and imaging. In the attached protocol we describe the methods of: 1) fixing brain tissue in situ via intracardial perfusion, 2) dissection and removal of whole brain, 3) stationary brain embedding in agarose, 4) precision semi-thick slice preparation using new vibratome instrumentation, 5) clearing brain tissue through a glycerol gradient, and 6) mounting on glass slides for light microscopy and z-stack reconstruction (Figure 1). For preparing brain slices we implemented a relatively new piece of instrumentation called the 'Compresstome' VF-200 (http://www.precisionary.com/products_vf200.html). This instrument is a semi-automated microtome equipped with a motorized advance and blade vibration system with features similar in function to other vibratomes. Unlike other vibratomes, the tissue to be sliced is mounted in an agarose plug within a stainless steel cylinder. The tissue is extruded at desired thicknesses from the cylinder, and cut by the forward advancing vibrating blade. The agarose plug/cylinder system allows for reproducible tissue mounting, alignment, and precision cutting. In our hands, the 'Compresstome' yields high quality tissue slices for electrophysiology, immunohistochemistry, and direct fixed-tissue mounting and imaging. Combined with optical clearing, here we demonstrate the preparation of semi-thick fixed brain slices for high-resolution fluorescent imaging.

A new high-resolution PET scanner dedicated to brain research

NASA Astrophysics Data System (ADS)

Watanabe, M.; Shimizu, K.; Omura, T.; Takahashi, M.; Kosugi, T.; Yoshikawa, E.; Sato, N.; Okada, H.; Yamashita, T.

2002-06-01

A high-resolution positron emission tomography (PET) scanner dedicated to brain studies has been developed and its physical performance was evaluated. The block detector consists of a new compact position-sensitive photomultiplier tube (PS-PMT, Hamamatsu R7600-C12) and an 8/spl times/4 bismuth germanate (BGO) array. The size of each crystal is 2.8 mm/spl times/6.55 mm/spl times/30 mm. The system has a total of 11 520 crystals arranged in 24 detector rings 508 mm in diameter (480 per ring). The field of view (FOV) is 330 mm in diameter/spl times/163 mm, which is sufficient to measure the entire human brain. The diameter of the scanner's opening is equal to the transaxial FOV (330 mm). The system can be operated in three-dimensional (3-D) data acquisition mode, when the slice septa are retracted. The mechanical motions of the gantry and bed are specially designed to measure the patient in various postures; lying, sitting, and even standing postures. The spatial resolution of 2.9 mm in both the transaxial and axial directions is obtained at the center of the FOV. The total system sensitivity is 6.4 kc/s/kBq/ml in two-dimensional (2-D) mode, with a 20-cm-diameter cylindrical phantom. The imaging capabilities of the scanner were studied with the Hoffman brain phantom and with a normal volunteer.

Power cavitation-guided blood-brain barrier opening with focused ultrasound and microbubbles

NASA Astrophysics Data System (ADS)

Burgess, M. T.; Apostolakis, I.; Konofagou, E. E.

2018-03-01

Image-guided monitoring of microbubble-based focused ultrasound (FUS) therapies relies on the accurate localization of FUS-stimulated microbubble activity (i.e. acoustic cavitation). Passive cavitation imaging with ultrasound arrays can achieve this, but with insufficient spatial resolution. In this study, we address this limitation and perform high-resolution monitoring of acoustic cavitation-mediated blood-brain barrier (BBB) opening with a new technique called power cavitation imaging. By synchronizing the FUS transmit and passive receive acquisition, high-resolution passive cavitation imaging was achieved by using delay and sum beamforming with absolute time delays. Since the axial image resolution is now dependent on the duration of the received acoustic cavitation emission, short pulses of FUS were used to limit its duration. Image sets were acquired at high-frame rates for calculation of power cavitation images analogous to power Doppler imaging. Power cavitation imaging displays the mean intensity of acoustic cavitation over time and was correlated with areas of acoustic cavitation-induced BBB opening. Power cavitation-guided BBB opening with FUS could constitute a standalone system that may not require MRI guidance during the procedure. The same technique can be used for other acoustic cavitation-based FUS therapies, for both safety and guidance.

Power cavitation-guided blood-brain barrier opening with focused ultrasound and microbubbles.

PubMed

Burgess, M T; Apostolakis, I; Konofagou, E E

2018-03-15

Image-guided monitoring of microbubble-based focused ultrasound (FUS) therapies relies on the accurate localization of FUS-stimulated microbubble activity (i.e. acoustic cavitation). Passive cavitation imaging with ultrasound arrays can achieve this, but with insufficient spatial resolution. In this study, we address this limitation and perform high-resolution monitoring of acoustic cavitation-mediated blood-brain barrier (BBB) opening with a new technique called power cavitation imaging. By synchronizing the FUS transmit and passive receive acquisition, high-resolution passive cavitation imaging was achieved by using delay and sum beamforming with absolute time delays. Since the axial image resolution is now dependent on the duration of the received acoustic cavitation emission, short pulses of FUS were used to limit its duration. Image sets were acquired at high-frame rates for calculation of power cavitation images analogous to power Doppler imaging. Power cavitation imaging displays the mean intensity of acoustic cavitation over time and was correlated with areas of acoustic cavitation-induced BBB opening. Power cavitation-guided BBB opening with FUS could constitute a standalone system that may not require MRI guidance during the procedure. The same technique can be used for other acoustic cavitation-based FUS therapies, for both safety and guidance.

A cellular perspective on brain energy metabolism and functional imaging.

PubMed

Magistretti, Pierre J; Allaman, Igor

2015-05-20

The energy demands of the brain are high: they account for at least 20% of the body's energy consumption. Evolutionary studies indicate that the emergence of higher cognitive functions in humans is associated with an increased glucose utilization and expression of energy metabolism genes. Functional brain imaging techniques such as fMRI and PET, which are widely used in human neuroscience studies, detect signals that monitor energy delivery and use in register with neuronal activity. Recent technological advances in metabolic studies with cellular resolution have afforded decisive insights into the understanding of the cellular and molecular bases of the coupling between neuronal activity and energy metabolism and point at a key role of neuron-astrocyte metabolic interactions. This article reviews some of the most salient features emerging from recent studies and aims at providing an integration of brain energy metabolism across resolution scales. Copyright © 2015 Elsevier Inc. All rights reserved.

Biomarker-guided translation of brain imaging into disease pathway models

PubMed Central

Younesi, Erfan; Hofmann-Apitius, Martin

2013-01-01

The advent of state-of-the-art brain imaging technologies in recent years and the ability of such technologies to provide high-resolution information at both structural and functional levels has spawned large efforts to introduce novel non-invasive imaging biomarkers for early prediction and diagnosis of brain disorders; however, their utility in both clinic and drug development at their best resolution remains limited to visualizing and monitoring disease progression. Given the fact that efficient translation of valuable information embedded in brain scans into clinical application is of paramount scientific and public health importance, a strategy is needed to bridge the current gap between imaging and molecular biology, particularly in neurodegenerative diseases. As an attempt to address this issue, we present a novel computational method to link readouts of imaging biomarkers to their underlying molecular pathways with the aim of guiding clinical diagnosis, prognosis and even target identification in drug discovery for Alzheimer's disease. PMID:24287435

Multichannel optical brain imaging to separate cerebral vascular, tissue metabolic, and neuronal effects of cocaine

NASA Astrophysics Data System (ADS)

Ren, Hugang; Luo, Zhongchi; Yuan, Zhijia; Pan, Yingtian; Du, Congwu

2012-02-01

Characterization of cerebral hemodynamic and oxygenation metabolic changes, as well neuronal function is of great importance to study of brain functions and the relevant brain disorders such as drug addiction. Compared with other neuroimaging modalities, optical imaging techniques have the potential for high spatiotemporal resolution and dissection of the changes in cerebral blood flow (CBF), blood volume (CBV), and hemoglobing oxygenation and intracellular Ca ([Ca2+]i), which serves as markers of vascular function, tissue metabolism and neuronal activity, respectively. Recently, we developed a multiwavelength imaging system and integrated it into a surgical microscope. Three LEDs of λ1=530nm, λ2=570nm and λ3=630nm were used for exciting [Ca2+]i fluorescence labeled by Rhod2 (AM) and sensitizing total hemoglobin (i.e., CBV), and deoxygenated-hemoglobin, whereas one LD of λ1=830nm was used for laser speckle imaging to form a CBF mapping of the brain. These light sources were time-sharing for illumination on the brain and synchronized with the exposure of CCD camera for multichannel images of the brain. Our animal studies indicated that this optical approach enabled simultaneous mapping of cocaine-induced changes in CBF, CBV and oxygenated- and deoxygenated hemoglobin as well as [Ca2+]i in the cortical brain. Its high spatiotemporal resolution (30μm, 10Hz) and large field of view (4x5 mm2) are advanced as a neuroimaging tool for brain functional study.

The Application of MRI for Depiction of Subtle Blood Brain Barrier Disruption in Stroke

PubMed Central

Israeli, David; Tanne, David; Daniels, Dianne; Last, David; Shneor, Ran; Guez, David; Landau, Efrat; Roth, Yiftach; Ocherashvilli, Aharon; Bakon, Mati; Hoffman, Chen; Weinberg, Amit; Volk, Talila; Mardor, Yael

2011-01-01

The development of imaging methodologies for detecting blood-brain-barrier (BBB) disruption may help predict stroke patient's propensity to develop hemorrhagic complications following reperfusion. We have developed a delayed contrast extravasation MRI-based methodology enabling real-time depiction of subtle BBB abnormalities in humans with high sensitivity to BBB disruption and high spatial resolution. The increased sensitivity to subtle BBB disruption is obtained by acquiring T1-weighted MRI at relatively long delays (~15 minutes) after contrast injection and subtracting from them images acquired immediately after contrast administration. In addition, the relatively long delays allow for acquisition of high resolution images resulting in high resolution BBB disruption maps. The sensitivity is further increased by image preprocessing with corrections for intensity variations and with whole body (rigid+elastic) registration. Since only two separate time points are required, the time between the two acquisitions can be used for acquiring routine clinical data, keeping the total imaging time to a minimum. A proof of concept study was performed in 34 patients with ischemic stroke and 2 patients with brain metastases undergoing high resolution T1-weighted MRI acquired at 3 time points after contrast injection. The MR images were pre-processed and subtracted to produce BBB disruption maps. BBB maps of patients with brain metastases and ischemic stroke presented different patterns of BBB opening. The significant advantage of the long extravasation time was demonstrated by a dynamic-contrast-enhancement study performed continuously for 18 min. The high sensitivity of our methodology enabled depiction of clear BBB disruption in 27% of the stroke patients who did not have abnormalities on conventional contrast-enhanced MRI. In 36% of the patients, who had abnormalities detectable by conventional MRI, the BBB disruption volumes were significantly larger in the maps than in conventional MRI. These results demonstrate the advantages of delayed contrast extravasation in increasing the sensitivity to subtle BBB disruption in ischemic stroke patients. The calculated disruption maps provide clear depiction of significant volumes of BBB disruption unattainable by conventional contrast-enhanced MRI. PMID:21209786

The application of MRI for depiction of subtle blood brain barrier disruption in stroke.

PubMed

Israeli, David; Tanne, David; Daniels, Dianne; Last, David; Shneor, Ran; Guez, David; Landau, Efrat; Roth, Yiftach; Ocherashvilli, Aharon; Bakon, Mati; Hoffman, Chen; Weinberg, Amit; Volk, Talila; Mardor, Yael

2010-12-26

The development of imaging methodologies for detecting blood-brain-barrier (BBB) disruption may help predict stroke patient's propensity to develop hemorrhagic complications following reperfusion. We have developed a delayed contrast extravasation MRI-based methodology enabling real-time depiction of subtle BBB abnormalities in humans with high sensitivity to BBB disruption and high spatial resolution. The increased sensitivity to subtle BBB disruption is obtained by acquiring T1-weighted MRI at relatively long delays (~15 minutes) after contrast injection and subtracting from them images acquired immediately after contrast administration. In addition, the relatively long delays allow for acquisition of high resolution images resulting in high resolution BBB disruption maps. The sensitivity is further increased by image preprocessing with corrections for intensity variations and with whole body (rigid+elastic) registration. Since only two separate time points are required, the time between the two acquisitions can be used for acquiring routine clinical data, keeping the total imaging time to a minimum. A proof of concept study was performed in 34 patients with ischemic stroke and 2 patients with brain metastases undergoing high resolution T1-weighted MRI acquired at 3 time points after contrast injection. The MR images were pre-processed and subtracted to produce BBB disruption maps. BBB maps of patients with brain metastases and ischemic stroke presented different patterns of BBB opening. The significant advantage of the long extravasation time was demonstrated by a dynamic-contrast-enhancement study performed continuously for 18 min. The high sensitivity of our methodology enabled depiction of clear BBB disruption in 27% of the stroke patients who did not have abnormalities on conventional contrast-enhanced MRI. In 36% of the patients, who had abnormalities detectable by conventional MRI, the BBB disruption volumes were significantly larger in the maps than in conventional MRI. These results demonstrate the advantages of delayed contrast extravasation in increasing the sensitivity to subtle BBB disruption in ischemic stroke patients. The calculated disruption maps provide clear depiction of significant volumes of BBB disruption unattainable by conventional contrast-enhanced MRI.

Quantifying structural alterations in Alzheimer's disease brains using quantitative phase imaging (Conference Presentation)

NASA Astrophysics Data System (ADS)

Lee, Moosung; Lee, Eeksung; Jung, JaeHwang; Yu, Hyeonseung; Kim, Kyoohyun; Yoon, Jonghee; Lee, Shinhwa; Jeong, Yong; Park, YongKeun

2017-02-01

Imaging brain tissues is an essential part of neuroscience because understanding brain structure provides relevant information about brain functions and alterations associated with diseases. Magnetic resonance imaging and positron emission tomography exemplify conventional brain imaging tools, but these techniques suffer from low spatial resolution around 100 μm. As a complementary method, histopathology has been utilized with the development of optical microscopy. The traditional method provides the structural information about biological tissues to cellular scales, but relies on labor-intensive staining procedures. With the advances of illumination sources, label-free imaging techniques based on nonlinear interactions, such as multiphoton excitations and Raman scattering, have been applied to molecule-specific histopathology. Nevertheless, these techniques provide limited qualitative information and require a pulsed laser, which is difficult to use for pathologists with no laser training. Here, we present a label-free optical imaging of mouse brain tissues for addressing structural alteration in Alzheimer's disease. To achieve the mesoscopic, unlabeled tissue images with high contrast and sub-micrometer lateral resolution, we employed holographic microscopy and an automated scanning platform. From the acquired hologram of the brain tissues, we could retrieve scattering coefficients and anisotropies according to the modified scattering-phase theorem. This label-free imaging technique enabled direct access to structural information throughout the tissues with a sub-micrometer lateral resolution and presented a unique means to investigate the structural changes in the optical properties of biological tissues.

Clinically relevant genetic biomarkers from the brain in alcoholism with representation on high resolution chromosome ideograms.

PubMed

Manzardo, Ann M; McGuire, Austen; Butler, Merlin G

2015-04-15

Alcoholism arises from combined effects of multiple biological factors including genetic and non-genetic causes with gene/environmental interaction. Intensive research and advanced genetic technology has generated a long list of genes and biomarkers involved in alcoholism neuropathology. These markers reflect complex overlapping and competing effects of possibly hundreds of genes which impact brain structure, function, biochemical alcohol processing, sensitivity and risk for dependence. We compiled a tabular list of clinically relevant genetic biomarkers for alcoholism targeting expression disturbances in the human brain through an extensive search of keywords related to alcoholism, alcohol abuse, and genetics from peer reviewed medical research articles and related nationally sponsored websites. Gene symbols were then placed on high resolution human chromosome ideograms with gene descriptions in tabular form. We identified 337 clinically relevant genetic biomarkers and candidate genes for alcoholism and alcohol-responsiveness from human brain research. Genetic biomarkers included neurotransmitter pathways associated with brain reward processes for dopaminergic (e.g., DRD2, MAOA, and COMT), serotoninergic (e.g., HTR3A, HTR1B, HTR3B, and SLC6A4), GABAergic (e.g., GABRA1, GABRA2, and GABRG1), glutaminergic (GAD1, GRIK3, and GRIN2C) and opioid (e.g., OPRM1, OPRD1, and OPRK1) pathways which presumably impact reinforcing properties of alcohol. Gene level disturbances in cellular and molecular networks impacted by alcohol and alcoholism pathology include transketolase (TKT), transferrin (TF), and myelin (e.g., MBP, MOBP, and MOG). High resolution chromosome ideograms provide investigators, physicians, geneticists and counselors a convenient visual image of the distribution of alcoholism genetic biomarkers from brain research with alphabetical listing of genes in tabular form allowing comparison between alcoholism-related phenotypes, and clinically-relevant alcoholism gene(s) at the chromosome band level to guide research, diagnosis, and treatment. Chromosome ideograms may facilitate gene-based personalized counseling of alcohol dependent individuals and their families. Copyright © 2015 Elsevier B.V. All rights reserved.

Three-dimensional high-resolution diffusion tensor imaging and tractography of the developing rabbit brain.

PubMed

D'Arceuil, Helen; Liu, Christina; Levitt, Pat; Thompson, Barbara; Kosofsky, Barry; de Crespigny, Alex

2008-01-01

Diffusion tensor imaging (DTI) is sensitive to structural ordering in brain tissue particularly in the white matter tracts. Diffusion anisotropy changes with disease and also with neural development. We used high-resolution DTI of fixed rabbit brains to study developmental changes in regional diffusion anisotropy and white matter fiber tract development. Imaging was performed on a 4.7-tesla Bruker Biospec Avance scanner using custom-built solenoid coils and DTI was performed at various postnatal ages. Trace apparent diffusion coefficient, fractional diffusion anisotropy maps and fiber tracts were generated and compared across the ages. The brain was highly anisotropic at birth and white matter anisotropy increased with age. Regional DTI tractography of the internal capsule showed refinement in regional tract architecture with maturation. Interestingly, brains with congenital deficiencies of the callosal commissure showed selectively strikingly different fiber architecture compared to age-matched brains. There was also some evidence of subcortical to cortical fiber connectivity. DTI tractography of the anterior and posterior limbs of the internal capsule showed reproducibly coherent fiber tracts corresponding to known corticospinal and corticobulbar tract anatomy. There was some minor interanimal tract variability, but there was remarkable similarity between the tracts in all animals. Therefore, ex vivo DTI tractography is a potentially powerful tool for neuroscience investigations and may also reveal effects (such as fiber tract pruning during development) which may be important targets for in vivo human studies. Copyright 2007 S. Karger AG, Basel.

Localization of synchronous cortical neural sources.

PubMed

Zerouali, Younes; Herry, Christophe L; Jemel, Boutheina; Lina, Jean-Marc

2013-03-01

Neural synchronization is a key mechanism to a wide variety of brain functions, such as cognition, perception, or memory. High temporal resolution achieved by EEG recordings allows the study of the dynamical properties of synchronous patterns of activity at a very fine temporal scale but with very low spatial resolution. Spatial resolution can be improved by retrieving the neural sources of EEG signal, thus solving the so-called inverse problem. Although many methods have been proposed to solve the inverse problem and localize brain activity, few of them target the synchronous brain regions. In this paper, we propose a novel algorithm aimed at localizing specifically synchronous brain regions and reconstructing the time course of their activity. Using multivariate wavelet ridge analysis, we extract signals capturing the synchronous events buried in the EEG and then solve the inverse problem on these signals. Using simulated data, we compare results of source reconstruction accuracy achieved by our method to a standard source reconstruction approach. We show that the proposed method performs better across a wide range of noise levels and source configurations. In addition, we applied our method on real dataset and identified successfully cortical areas involved in the functional network underlying visual face perception. We conclude that the proposed approach allows an accurate localization of synchronous brain regions and a robust estimation of their activity.

TH-EF-207A-06: High-Resolution Optical-CT/ECT Imaging of Unstained Mice Femur, Brain, Spleen, and Tumor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yoon, S; Dewhirst, M; Oldham, M

2016-06-15

Purpose: Optical transmission and emission computed tomography (optical-CT/ECT) provides high-resolution 3D attenuation and emission maps in unsectioned large (∼1cm{sup 3}) ex vivo tissue samples at a resolution of 12.9µm{sup 3} per voxel. Here we apply optical-CT/ECT to investigate high-resolution structure and auto-fluorescence in a range of optically cleared mice organs, including, for the first time, mouse bone (femur), opening the potential for study of bone metastasis and bone-mediated immune response. Methods: Three BALBc mice containing 4T1 flank tumors were sacrificed to obtain spleen, brain, tumor, and femur. Tissues were washed in 4% PFA, fixed in EtOH solution (for 5, 10,more » 10, and 2 days respectively), and then optically cleared for 3 days in BABBs. The femur was also placed in 0.25M aqueous EDTA for 15–30 days to remove calcium. Optical-CT/ECT attenuation and emission maps at 633nm (the latter using 530nm excitation light) were obtained for all samples. Bi-telecentric optical-CT was compared side-by-side with conventional optical projection tomography (OPT) imaging to evaluate imaging capability of these two rival techniques. Results: Auto-fluorescence mapping of femurs reveals vasculatures and fluorescence heterogeneity. High signals (A.U.=10) are reported in the medullary cavity but not in the cortical bone (A.U.=1). The brain strongly and uniform auto-fluoresces (A.U.=5). Thick, optically dense organs such as the spleen and the tumor (0.12, 0.46OD/mm) are reconstructed at depth without significant loss of resolution, which we attribute to the bi-telecentric optics of optical-CT. The attenuation map of tumor reveals vasculature, attenuation heterogeneity, and possibly necrotic tissue. Conclusion: We demonstrate the feasibility of optical-CT/ECT imaging of un-sectioned mice bones (femurs) and spleen with high resolution. This result, and the characterization of unstained organs, are important steps enabling future studies involving optical-CT/ECT applied to study metastasis and immunologic responses via fluorescence staining.« less

Modeling brain circuitry over a wide range of scales.

PubMed

Fua, Pascal; Knott, Graham W

2015-01-01

If we are ever to unravel the mysteries of brain function at its most fundamental level, we will need a precise understanding of how its component neurons connect to each other. Electron Microscopes (EM) can now provide the nanometer resolution that is needed to image synapses, and therefore connections, while Light Microscopes (LM) see at the micrometer resolution required to model the 3D structure of the dendritic network. Since both the topology and the connection strength are integral parts of the brain's wiring diagram, being able to combine these two modalities is critically important. In fact, these microscopes now routinely produce high-resolution imagery in such large quantities that the bottleneck becomes automated processing and interpretation, which is needed for such data to be exploited to its full potential. In this paper, we briefly review the Computer Vision techniques we have developed at EPFL to address this need. They include delineating dendritic arbors from LM imagery, segmenting organelles from EM, and combining the two into a consistent representation.

Modeling brain circuitry over a wide range of scales

PubMed Central

Fua, Pascal; Knott, Graham W.

2015-01-01

If we are ever to unravel the mysteries of brain function at its most fundamental level, we will need a precise understanding of how its component neurons connect to each other. Electron Microscopes (EM) can now provide the nanometer resolution that is needed to image synapses, and therefore connections, while Light Microscopes (LM) see at the micrometer resolution required to model the 3D structure of the dendritic network. Since both the topology and the connection strength are integral parts of the brain's wiring diagram, being able to combine these two modalities is critically important. In fact, these microscopes now routinely produce high-resolution imagery in such large quantities that the bottleneck becomes automated processing and interpretation, which is needed for such data to be exploited to its full potential. In this paper, we briefly review the Computer Vision techniques we have developed at EPFL to address this need. They include delineating dendritic arbors from LM imagery, segmenting organelles from EM, and combining the two into a consistent representation. PMID:25904852

Comparative assessments of the effects of alcohol exposure on fetal brain development using optical coherence tomography and ultrasound imaging

NASA Astrophysics Data System (ADS)

Sudheendran, Narendran; Bake, Shameena; Miranda, Rajesh C.; Larin, Kirill V.

2013-02-01

The developing fetal brain is vulnerable to a variety of environmental agents including maternal ethanol consumption. Preclinical studies on the development and amelioration of fetal teratology would be significantly facilitated by the application of high resolution imaging technologies like optical coherence tomography (OCT) and high-frequency ultrasound (US). This study investigates the ability of these imaging technologies to measure the effects of maternal ethanol exposure on brain development, ex vivo, in fetal mice. Pregnant mice at gestational day 12.5 were administered ethanol (3 g/Kg b.wt.) or water by intragastric gavage, twice daily for three consecutive days. On gestational day 14.5, fetuses were collected and imaged. Three-dimensional images of the mice fetus brains were obtained by OCT and high-resolution US, and the volumes of the left and right ventricles of the brain were measured. Ethanol-exposed fetuses exhibited a statistically significant, 2-fold increase in average left and right ventricular volumes compared with the ventricular volume of control fetuses, with OCT-derived measures of 0.38 and 0.18 mm3, respectively, whereas the boundaries of the fetal mouse lateral ventricles were not clearly definable with US imaging. Our results indicate that OCT is a useful technology for assessing ventriculomegaly accompanying alcohol-induced developmental delay. This study clearly demonstrated advantages of using OCT for quantitative assessment of embryonic development compared with US imaging.

Fully integrated silicon probes for high-density recording of neural activity.

PubMed

Jun, James J; Steinmetz, Nicholas A; Siegle, Joshua H; Denman, Daniel J; Bauza, Marius; Barbarits, Brian; Lee, Albert K; Anastassiou, Costas A; Andrei, Alexandru; Aydın, Çağatay; Barbic, Mladen; Blanche, Timothy J; Bonin, Vincent; Couto, João; Dutta, Barundeb; Gratiy, Sergey L; Gutnisky, Diego A; Häusser, Michael; Karsh, Bill; Ledochowitsch, Peter; Lopez, Carolina Mora; Mitelut, Catalin; Musa, Silke; Okun, Michael; Pachitariu, Marius; Putzeys, Jan; Rich, P Dylan; Rossant, Cyrille; Sun, Wei-Lung; Svoboda, Karel; Carandini, Matteo; Harris, Kenneth D; Koch, Christof; O'Keefe, John; Harris, Timothy D

2017-11-08

Sensory, motor and cognitive operations involve the coordinated action of large neuronal populations across multiple brain regions in both superficial and deep structures. Existing extracellular probes record neural activity with excellent spatial and temporal (sub-millisecond) resolution, but from only a few dozen neurons per shank. Optical Ca 2+ imaging offers more coverage but lacks the temporal resolution needed to distinguish individual spikes reliably and does not measure local field potentials. Until now, no technology compatible with use in unrestrained animals has combined high spatiotemporal resolution with large volume coverage. Here we design, fabricate and test a new silicon probe known as Neuropixels to meet this need. Each probe has 384 recording channels that can programmably address 960 complementary metal-oxide-semiconductor (CMOS) processing-compatible low-impedance TiN sites that tile a single 10-mm long, 70 × 20-μm cross-section shank. The 6 × 9-mm probe base is fabricated with the shank on a single chip. Voltage signals are filtered, amplified, multiplexed and digitized on the base, allowing the direct transmission of noise-free digital data from the probe. The combination of dense recording sites and high channel count yielded well-isolated spiking activity from hundreds of neurons per probe implanted in mice and rats. Using two probes, more than 700 well-isolated single neurons were recorded simultaneously from five brain structures in an awake mouse. The fully integrated functionality and small size of Neuropixels probes allowed large populations of neurons from several brain structures to be recorded in freely moving animals. This combination of high-performance electrode technology and scalable chip fabrication methods opens a path towards recording of brain-wide neural activity during behaviour.

Fully Integrated Silicon Probes for High-Density Recording of Neural Activity

PubMed Central

Jun, James J.; Steinmetz, Nicholas A.; Siegle, Joshua H.; Denman, Daniel J.; Bauza, Marius; Barbarits, Brian; Lee, Albert K.; Anastassiou, Costas A.; Andrei, Alexandru; Aydın, Çağatay; Barbic, Mladen; Blanche, Timothy J.; Bonin, Vincent; Couto, João; Dutta, Barundeb; Gratiy, Sergey L.; Gutnisky, Diego A.; Häusser, Michael; Karsh, Bill; Ledochowitsch, Peter; Lopez, Carolina Mora; Mitelut, Catalin; Musa, Silke; Okun, Michael; Pachitariu, Marius; Putzeys, Jan; Rich, P. Dylan; Rossant, Cyrille; Sun, Wei-lung; Svoboda, Karel; Carandini, Matteo; Harris, Kenneth D.; Koch, Christof; O'Keefe, John; Harris, Timothy D.

2018-01-01

Summary Paragraph Sensory, motor, and cognitive operations involve the coordinated action of large neuronal populations across multiple brain regions in both superficial and deep structures1,2. Existing extracellular probes record neural activity with excellent spatial and temporal (sub-millisecond) resolution but from only a few dozen neurons per shank. Optical Ca2+ imaging3–5 offers more coverage but lacks the temporal resolution to reliably distinguish individual spikes and does not measure local field potentials. To date, no technology compatible with unrestrained animals has combined high spatiotemporal resolution with large volume coverage. To satisfy this need, we designed, fabricated, and tested a new silicon probe called Neuropixels. Each probe has 384 recording channels that can programmably address 960 CMOS processing-compatible low-impedance TiN6 sites that tile a single 10 mm long, 70x20 µm cross section shank. The 6x9 mm probe base is fabricated with the shank on a single chip. Voltage signals are filtered, amplified, multiplexed, and digitized on the base, allowing noise-free digital data transmission directly from the probe. The combination of dense recording sites and high channel count yielded well-isolated spiking activity from hundreds of neurons per probe implanted in mice and rats. Using two probes, more than 700 well-isolated single neurons were simultaneously recorded from five brain structures in an awake mouse. The fully integrated functionality and small size of Neuropixels probes allowed recording large populations of neurons from multiple brain structures in freely moving animals. This combination of high-performance electrode technology and scalable chip fabrication methods opens the path to record brain-wide neural activity during behavior. PMID:29120427

3D Reconstructed Cyto-, Muscarinic M2 Receptor, and Fiber Architecture of the Rat Brain Registered to the Waxholm Space Atlas

PubMed Central

Schubert, Nicole; Axer, Markus; Schober, Martin; Huynh, Anh-Minh; Huysegoms, Marcel; Palomero-Gallagher, Nicola; Bjaalie, Jan G.; Leergaard, Trygve B.; Kirlangic, Mehmet E.; Amunts, Katrin; Zilles, Karl

2016-01-01

High-resolution multiscale and multimodal 3D models of the brain are essential tools to understand its complex structural and functional organization. Neuroimaging techniques addressing different aspects of brain organization should be integrated in a reference space to enable topographically correct alignment and subsequent analysis of the various datasets and their modalities. The Waxholm Space (http://software.incf.org/software/waxholm-space) is a publicly available 3D coordinate-based standard reference space for the mapping and registration of neuroanatomical data in rodent brains. This paper provides a newly developed pipeline combining imaging and reconstruction steps with a novel registration strategy to integrate new neuroimaging modalities into the Waxholm Space atlas. As a proof of principle, we incorporated large scale high-resolution cyto-, muscarinic M2 receptor, and fiber architectonic images of rat brains into the 3D digital MRI based atlas of the Sprague Dawley rat in Waxholm Space. We describe the whole workflow, from image acquisition to reconstruction and registration of these three modalities into the Waxholm Space rat atlas. The registration of the brain sections into the atlas is performed by using both linear and non-linear transformations. The validity of the procedure is qualitatively demonstrated by visual inspection, and a quantitative evaluation is performed by measurement of the concordance between representative atlas-delineated regions and the same regions based on receptor or fiber architectonic data. This novel approach enables for the first time the generation of 3D reconstructed volumes of nerve fibers and fiber tracts, or of muscarinic M2 receptor density distributions, in an entire rat brain. Additionally, our pipeline facilitates the inclusion of further neuroimaging datasets, e.g., 3D reconstructed volumes of histochemical stainings or of the regional distributions of multiple other receptor types, into the Waxholm Space. Thereby, a multiscale and multimodal rat brain model was created in the Waxholm Space atlas of the rat brain. Since the registration of these multimodal high-resolution datasets into the same coordinate system is an indispensable requisite for multi-parameter analyses, this approach enables combined studies on receptor and cell distributions as well as fiber densities in the same anatomical structures at microscopic scales for the first time. PMID:27199682

3D Reconstructed Cyto-, Muscarinic M2 Receptor, and Fiber Architecture of the Rat Brain Registered to the Waxholm Space Atlas.

PubMed

Schubert, Nicole; Axer, Markus; Schober, Martin; Huynh, Anh-Minh; Huysegoms, Marcel; Palomero-Gallagher, Nicola; Bjaalie, Jan G; Leergaard, Trygve B; Kirlangic, Mehmet E; Amunts, Katrin; Zilles, Karl

2016-01-01

High-resolution multiscale and multimodal 3D models of the brain are essential tools to understand its complex structural and functional organization. Neuroimaging techniques addressing different aspects of brain organization should be integrated in a reference space to enable topographically correct alignment and subsequent analysis of the various datasets and their modalities. The Waxholm Space (http://software.incf.org/software/waxholm-space) is a publicly available 3D coordinate-based standard reference space for the mapping and registration of neuroanatomical data in rodent brains. This paper provides a newly developed pipeline combining imaging and reconstruction steps with a novel registration strategy to integrate new neuroimaging modalities into the Waxholm Space atlas. As a proof of principle, we incorporated large scale high-resolution cyto-, muscarinic M2 receptor, and fiber architectonic images of rat brains into the 3D digital MRI based atlas of the Sprague Dawley rat in Waxholm Space. We describe the whole workflow, from image acquisition to reconstruction and registration of these three modalities into the Waxholm Space rat atlas. The registration of the brain sections into the atlas is performed by using both linear and non-linear transformations. The validity of the procedure is qualitatively demonstrated by visual inspection, and a quantitative evaluation is performed by measurement of the concordance between representative atlas-delineated regions and the same regions based on receptor or fiber architectonic data. This novel approach enables for the first time the generation of 3D reconstructed volumes of nerve fibers and fiber tracts, or of muscarinic M2 receptor density distributions, in an entire rat brain. Additionally, our pipeline facilitates the inclusion of further neuroimaging datasets, e.g., 3D reconstructed volumes of histochemical stainings or of the regional distributions of multiple other receptor types, into the Waxholm Space. Thereby, a multiscale and multimodal rat brain model was created in the Waxholm Space atlas of the rat brain. Since the registration of these multimodal high-resolution datasets into the same coordinate system is an indispensable requisite for multi-parameter analyses, this approach enables combined studies on receptor and cell distributions as well as fiber densities in the same anatomical structures at microscopic scales for the first time.

Application of optical coherence tomography based microangiography for cerebral imaging

NASA Astrophysics Data System (ADS)

Baran, Utku; Wang, Ruikang K.

2016-03-01

Requirements of in vivo rodent brain imaging are hard to satisfy using traditional technologies such as magnetic resonance imaging and two-photon microscopy. Optical coherence tomography (OCT) is an emerging tool that can easily reach at high speeds and provide high resolution volumetric images with a relatively large field of view for rodent brain imaging. Here, we provide the overview of recent developments of functional OCT based imaging techniques for neuroscience applications on rodents. Moreover, a summary of OCT-based microangiography (OMAG) studies for stroke and traumatic brain injury cases on rodents are provided.

Single unit approaches to human vision and memory.

PubMed

Kreiman, Gabriel

2007-08-01

Research on the visual system focuses on using electrophysiology, pharmacology and other invasive tools in animal models. Non-invasive tools such as scalp electroencephalography and imaging allow examining humans but show a much lower spatial and/or temporal resolution. Under special clinical conditions, it is possible to monitor single-unit activity in humans when invasive procedures are required due to particular pathological conditions including epilepsy and Parkinson's disease. We review our knowledge about the visual system and visual memories in the human brain at the single neuron level. The properties of the human brain seem to be broadly compatible with the knowledge derived from animal models. The possibility of examining high-resolution brain activity in conscious human subjects allows investigators to ask novel questions that are challenging to address in animal models.

Functional ultrasound imaging of intrinsic connectivity in the living rat brain with high spatiotemporal resolution

PubMed Central

Osmanski, Bruno-Félix; Pezet, Sophie; Ricobaraza, Ana; Lenkei, Zsolt; Tanter, Mickael

2014-01-01

Long-range coherences in spontaneous brain activity reflect functional connectivity. Here we propose a novel, highly resolved connectivity mapping approach, using ultrafast functional ultrasound (fUS), which enables imaging of cerebral microvascular haemodynamics deep in the anaesthetized rodent brain, through a large thinned-skull cranial window, with pixel dimensions of 100 μm × 100 μm in-plane. The millisecond-range temporal resolution allows unambiguous cancellation of low-frequency cardio-respiratory noise. Both seed-based and singular value decomposition analysis of spatial coherences in the low-frequency (<0.1 Hz) spontaneous fUS signal fluctuations reproducibly report, at different coronal planes, overlapping high-contrast, intrinsic functional connectivity patterns. These patterns are similar to major functional networks described in humans by resting-state fMRI, such as the lateral task-dependent network putatively anticorrelated with the midline default-mode network. These results introduce fUS as a powerful novel neuroimaging method, which could be extended to portable systems for three-dimensional functional connectivity imaging in awake and freely moving rodents. PMID:25277668

3D surface rendered MR images of the brain and its vasculature.

PubMed

Cline, H E; Lorensen, W E; Souza, S P; Jolesz, F A; Kikinis, R; Gerig, G; Kennedy, T E

1991-01-01

Both time-of-flight and phase contrast magnetic resonance angiography images are combined with stationary tissue images to provide data depicting two contrast relationships yielding intrinsic discrimination of brain matter and flowing blood. A computer analysis is based on nearest neighbor segmentation and the connection between anatomical structures to partition the images into different tissue categories: from which, high resolution brain parenchymal and vascular surfaces are constructed and rendered in juxtaposition, aiding in surgical planning.

The metabolism of the human brain studied with positron emission tomography

DOE Office of Scientific and Technical Information (OSTI.GOV)

Greitz, T.; Ingvar, D.H.; Widen, L.

1985-01-01

This volume presents coverage of the use of positron emission tomography (PET) to study the human brain. The contributors assess new developments in high-resolution positron emission tomography, cyclotrons, radiochemistry, and tracer kinetic models, and explore the use of PET in brain energy metabolism, blood flow, and protein synthesis measurements, receptor analysis, and pH determinations, In addition, they discuss the relevance and applications of positron emission tomography from the perspectives of physiology, neurology, and psychiatry.

Whole-central nervous system functional imaging in larval Drosophila

PubMed Central

Lemon, William C.; Pulver, Stefan R.; Höckendorf, Burkhard; McDole, Katie; Branson, Kristin; Freeman, Jeremy; Keller, Philipp J.

2015-01-01

Understanding how the brain works in tight concert with the rest of the central nervous system (CNS) hinges upon knowledge of coordinated activity patterns across the whole CNS. We present a method for measuring activity in an entire, non-transparent CNS with high spatiotemporal resolution. We combine a light-sheet microscope capable of simultaneous multi-view imaging at volumetric speeds 25-fold faster than the state-of-the-art, a whole-CNS imaging assay for the isolated Drosophila larval CNS and a computational framework for analysing multi-view, whole-CNS calcium imaging data. We image both brain and ventral nerve cord, covering the entire CNS at 2 or 5 Hz with two- or one-photon excitation, respectively. By mapping network activity during fictive behaviours and quantitatively comparing high-resolution whole-CNS activity maps across individuals, we predict functional connections between CNS regions and reveal neurons in the brain that identify type and temporal state of motor programs executed in the ventral nerve cord. PMID:26263051

Ultrahigh-resolution imaging of the human brain with phase-cycled balanced steady-state free precession at 7 T.

PubMed

Zeineh, Michael M; Parekh, Mansi B; Zaharchuk, Greg; Su, Jason H; Rosenberg, Jarrett; Fischbein, Nancy J; Rutt, Brian K

2014-05-01

The objectives of this study were to acquire ultra-high resolution images of the brain using balanced steady-state free precession (bSSFP) at 7 T and to identify the potential utility of this sequence. Eight volunteers participated in this study after providing informed consent. Each volunteer was scanned with 8 phase cycles of bSSFP at 0.4-mm isotropic resolution using 0.5 number of excitations and 2-dimensional parallel acceleration of 1.75 × 1.75. Each phase cycle required 5 minutes of scanning, with pauses between the phase cycles allowing short periods of rest. The individual phase cycles were aligned and then averaged. The same volunteers underwent scanning using 3-dimensional (3D) multiecho gradient recalled echo at 0.8-mm isotropic resolution, 3D Cube T2 at 0.7-mm isotropic resolution, and thin-section coronal oblique T2-weighted fast spin echo at 0.22 × 0.22 × 2.0-mm resolution for comparison. Two neuroradiologists assessed image quality and potential research and clinical utility. The volunteers generally tolerated the scan sessions well, and composite high-resolution bSSFP images were produced for each volunteer. Rater analysis demonstrated that bSSFP had a superior 3D visualization of the microarchitecture of the hippocampus, very good contrast to delineate the borders of the subthalamic nucleus, and relatively good B1 homogeneity throughout. In addition to an excellent visualization of the cerebellum, subtle details of the brain and skull base anatomy were also easier to identify on the bSSFP images, including the line of Gennari, membrane of Liliequist, and cranial nerves. Balanced steady-state free precession had a strong iron contrast similar to or better than the comparison sequences. However, cortical gray-white contrast was significantly better with Cube T2 and T2-weighted fast spin echo. Balanced steady-state free precession can facilitate ultrahigh-resolution imaging of the brain. Although total imaging times are long, the individually short phase cycles can be acquired separately, improving examination tolerability. These images may be beneficial for studies of the hippocampus, iron-containing structures such as the subthalamic nucleus and line of Gennari, and the basal cisterns and their contents.

Preliminary evaluation of a monolithic detector module for integrated PET/MRI scanner with high spatial resolution

NASA Astrophysics Data System (ADS)

Pani, R.; Gonzalez, A. J.; Bettiol, M.; Fabbri, A.; Cinti, M. N.; Preziosi, E.; Borrazzo, C.; Conde, P.; Pellegrini, R.; Di Castro, E.; Majewski, S.

2015-06-01

The proposal of Mindview European Project concerns with the development of a very high resolution and high efficiency brain dedicated PET scanner simultaneously working with a Magnetic Resonance scanner, that expects to visualize neurotransmitter pathways and their disruptions in the quest to better diagnose schizophrenia. On behalf of this project, we propose a low cost PET module for the first prototype, based on monolithic crystals, suitable to be integrated with a head Radio Frequency (RF) coil. The aim of the suggested module is to achieve high performances in terms of efficiency, planar spatial resolution (expected about 1 mm) and discrimination of gamma Depth Of Interaction (DOI) in order to reduce the parallax error. Our preliminary results are very promising: a DOI resolution of about 3 mm, a spatial resolution ranging from about 1 to 1.5 mm and a good position linearity.

Cortical fibers orientation mapping using in-vivo whole brain 7 T diffusion MRI.

PubMed

Gulban, Omer F; De Martino, Federico; Vu, An T; Yacoub, Essa; Uğurbil, Kamil; Lenglet, Christophe

2018-05-10

Diffusion MRI of the cortical gray matter is challenging because the micro-environment probed by water molecules is much more complex than within the white matter. High spatial and angular resolutions are therefore necessary to uncover anisotropic diffusion patterns and laminar structures, which provide complementary (e.g. to anatomical and functional MRI) microstructural information about the cortex architectonic. Several ex-vivo and in-vivo MRI studies have recently addressed this question, however predominantly with an emphasis on specific cortical areas. There is currently no whole brain in-vivo data leveraging multi-shell diffusion MRI acquisition at high spatial resolution, and depth dependent analysis, to characterize the complex organization of cortical fibers. Here, we present unique in-vivo human 7T diffusion MRI data, and a dedicated cortical depth dependent analysis pipeline. We leverage the high spatial (1.05 mm isotropic) and angular (198 diffusion gradient directions) resolution of this whole brain dataset to improve cortical fiber orientations mapping, and study neurites (axons and/or dendrites) trajectories across cortical depths. Tangential fibers in superficial cortical depths and crossing fiber configurations in deep cortical depths are identified. Fibers gradually inserting into the gyral walls are visualized, which contributes to mitigating the gyral bias effect. Quantitative radiality maps and histograms in individual subjects and cortex-based aligned datasets further support our results. Copyright © 2018 Elsevier Inc. All rights reserved.

Optically based quantification of absolute cerebral metabolic rate of oxygen (CMRO2) with high spatial resolution in rodents

NASA Astrophysics Data System (ADS)

Yaseen, Mohammad A.; Srinivasan, Vivek J.; Sakadžić, Sava; Vinogradov, Sergei A.; Boas, David A.

2010-02-01

Measuring oxygen delivery in brain tissue is important for identifying the pathophysiological changes associated with brain injury and various diseases such as cancer, stroke, and Alzheimer's disease. We have developed a multi-modal imaging system for minimally invasive measurement of cerebral oxygenation and blood flow in small animals with high spatial resolution. The system allows for simultaneous measurement of blood flow using Fourier-domain optical coherence tomography, and oxygen partial pressure (pO2) using either confocal or multiphoton phosphorescence lifetime imaging with exogenous porphyrin-based dyes sensitive to dissolved oxygen. Here we present the changes in pO2 and blood flow in superficial cortical vessels of Sprague Dawley rats in response to conditions such as hypoxia, hyperoxia, and functional stimulation. pO2 measurements display considerable heterogeneity over distances that cannot be resolved with more widely used oxygen-monitoring techniques such as BOLD-fMRI. Large increases in blood flow are observed in response to functional stimulation and hypoxia. Our system allows for quantification of cerebral metabolic rate of oxygen (CMRO2) with high spatial resolution, providing a better understanding of metabolic dynamics during functional stimulation and under various neuropathologies. Ultimately, better insight into the underlying mechanisms of neuropathologies will facilitate the development of improved therapeutic strategies to minimize damage to brain tissue.

3D Data Mapping and Real-Time Experiment Control and Visualization in Brain Slices.

PubMed

Navarro, Marco A; Hibbard, Jaime V K; Miller, Michael E; Nivin, Tyler W; Milescu, Lorin S

2015-10-20

Here, we propose two basic concepts that can streamline electrophysiology and imaging experiments in brain slices and enhance data collection and analysis. The first idea is to interface the experiment with a software environment that provides a 3D scene viewer in which the experimental rig, the brain slice, and the recorded data are represented to scale. Within the 3D scene viewer, the user can visualize a live image of the sample and 3D renderings of the recording electrodes with real-time position feedback. Furthermore, the user can control the instruments and visualize their status in real time. The second idea is to integrate multiple types of experimental data into a spatial and temporal map of the brain slice. These data may include low-magnification maps of the entire brain slice, for spatial context, or any other type of high-resolution structural and functional image, together with time-resolved electrical and optical signals. The entire data collection can be visualized within the 3D scene viewer. These concepts can be applied to any other type of experiment in which high-resolution data are recorded within a larger sample at different spatial and temporal coordinates. Copyright © 2015 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Postmortem diffusion MRI of the human brainstem and thalamus for deep brain stimulator electrode localization.

PubMed

Calabrese, Evan; Hickey, Patrick; Hulette, Christine; Zhang, Jingxian; Parente, Beth; Lad, Shivanand P; Johnson, G Allan

2015-08-01

Deep brain stimulation (DBS) is an established surgical therapy for medically refractory tremor disorders including essential tremor (ET) and is currently under investigation for use in a variety of other neurologic and psychiatric disorders. There is growing evidence that the anti-tremor effects of DBS for ET are directly related to modulation of the dentatorubrothalamic tract (DRT), a white matter pathway that connects the cerebellum, red nucleus, and ventral intermediate nucleus of the thalamus. Emerging white matter targets for DBS, like the DRT, will require improved three-dimensional (3D) reference maps of deep brain anatomy and structural connectivity for accurate electrode targeting. High-resolution diffusion MRI of postmortem brain specimens can provide detailed volumetric images of important deep brain nuclei and 3D reconstructions of white matter pathways with probabilistic tractography techniques. We present a high spatial and angular resolution diffusion MRI template of the postmortem human brainstem and thalamus with 3D reconstructions of the nuclei and white matter tracts involved in ET circuitry. We demonstrate registration of these data to in vivo, clinical images from patients receiving DBS therapy, and correlate electrode proximity to tractography of the DRT with improvement of ET symptoms. © 2015 Wiley Periodicals, Inc.

Orbitrap mass spectrometry characterization of hybrid chondroitin/dermatan sulfate hexasaccharide domains expressed in brain.

PubMed

Robu, Adrian C; Popescu, Laurentiu; Munteanu, Cristian V A; Seidler, Daniela G; Zamfir, Alina D

2015-09-15

In the central nervous system, chondroitin/dermatan sulfate (CS/DS) glycosaminoglycans (GAGs) modulate neurotrophic effects and glial cell maturation during brain development. Previous reports revealed that GAG composition could be responsible for CS/DS activities in brain. In this work, for the structural characterization of DS- and CS-rich domains in hybrid GAG chains extracted from neural tissue, we have developed an advanced approach based on high-resolution mass spectrometry (MS) using nanoelectrospray ionization Orbitrap in the negative ion mode. Our high-resolution MS and multistage MS approach was developed and applied to hexasaccharides obtained from 4- and 14-week-old mouse brains by GAG digestion with chondroitin B and in parallel with AC I lyase. The expression of DS- and CS-rich domains in the two tissues was assessed comparatively. The analyses indicated an age-related structural variability of the CS/DS motifs. The older brain was found to contain more structures and a higher sulfation of DS-rich regions, whereas the younger brain was found to be characterized by a higher sulfation of CS-rich regions. By multistage MS using collision-induced dissociation, we also demonstrated the incidence in mouse brain of an atypical [4,5-Δ-GlcAGalNAc(IdoAGalNAc)2], presenting a bisulfated CS disaccharide formed by 3-O-sulfate-4,5-Δ-GlcA and 6-O-sulfate-GalNAc moieties. Copyright © 2015 Elsevier Inc. All rights reserved.

Towards High-Resolution Tissue Imaging Using Nanospray Desorption Electrospray Ionization Mass Spectrometry Coupled to Shear Force Microscopy

NASA Astrophysics Data System (ADS)

Nguyen, Son N.; Sontag, Ryan L.; Carson, James P.; Corley, Richard A.; Ansong, Charles; Laskin, Julia

2018-02-01

Constant mode ambient mass spectrometry imaging (MSI) of tissue sections with high lateral resolution of better than 10 μm was performed by combining shear force microscopy with nanospray desorption electrospray ionization (nano-DESI). Shear force microscopy enabled precise control of the distance between the sample and nano-DESI probe during MSI experiments and provided information on sample topography. Proof-of-concept experiments were performed using lung and brain tissue sections representing spongy and dense tissues, respectively. Topography images obtained using shear force microscopy were comparable to the results obtained using contact profilometry over the same region of the tissue section. Variations in tissue height were found to be dependent on the tissue type and were in the range of 0-5 μm for lung tissue and 0-3 μm for brain tissue sections. Ion images of phospholipids obtained in this study are in good agreement with literature data. Normalization of nano-DESI MSI images to the signal of the internal standard added to the extraction solvent allowed us to construct high-resolution ion images free of matrix effects.

Simple platform for chronic imaging of hippocampal activity during spontaneous behaviour in an awake mouse

PubMed Central

Villette, Vincent; Levesque, Mathieu; Miled, Amine; Gosselin, Benoit; Topolnik, Lisa

2017-01-01

Chronic electrophysiological recordings of neuronal activity combined with two-photon Ca2+ imaging give access to high resolution and cellular specificity. In addition, awake drug-free experimentation is required for investigating the physiological mechanisms that operate in the brain. Here, we developed a simple head fixation platform, which allows simultaneous chronic imaging and electrophysiological recordings to be obtained from the hippocampus of awake mice. We performed quantitative analyses of spontaneous animal behaviour, the associated network states and the cellular activities in the dorsal hippocampus as well as estimated the brain stability limits to image dendritic processes and individual axonal boutons. Ca2+ imaging recordings revealed a relatively stereotyped hippocampal activity despite a high inter-animal and inter-day variability in the mouse behavior. In addition to quiet state and locomotion behavioural patterns, the platform allowed the reliable detection of walking steps and fine speed variations. The brain motion during locomotion was limited to ~1.8 μm, thus allowing for imaging of small sub-cellular structures to be performed in parallel with recordings of network and behavioural states. This simple device extends the drug-free experimentation in vivo, enabling high-stability optophysiological experiments with single-bouton resolution in the mouse awake brain. PMID:28240275

Rotating single-shot acquisition (RoSA) with composite reconstruction for fast high-resolution diffusion imaging.

PubMed

Wen, Qiuting; Kodiweera, Chandana; Dale, Brian M; Shivraman, Giri; Wu, Yu-Chien

2018-01-01

To accelerate high-resolution diffusion imaging, rotating single-shot acquisition (RoSA) with composite reconstruction is proposed. Acceleration was achieved by acquiring only one rotating single-shot blade per diffusion direction, and high-resolution diffusion-weighted (DW) images were reconstructed by using similarities of neighboring DW images. A parallel imaging technique was implemented in RoSA to further improve the image quality and acquisition speed. RoSA performance was evaluated by simulation and human experiments. A brain tensor phantom was developed to determine an optimal blade size and rotation angle by considering similarity in DW images, off-resonance effects, and k-space coverage. With the optimal parameters, RoSA MR pulse sequence and reconstruction algorithm were developed to acquire human brain data. For comparison, multishot echo planar imaging (EPI) and conventional single-shot EPI sequences were performed with matched scan time, resolution, field of view, and diffusion directions. The simulation indicated an optimal blade size of 48 × 256 and a 30 ° rotation angle. For 1 × 1 mm 2 in-plane resolution, RoSA was 12 times faster than the multishot acquisition with comparable image quality. With the same acquisition time as SS-EPI, RoSA provided superior image quality and minimum geometric distortion. RoSA offers fast, high-quality, high-resolution diffusion images. The composite image reconstruction is model-free and compatible with various diffusion computation approaches including parametric and nonparametric analyses. Magn Reson Med 79:264-275, 2018. © 2017 International Society for Magnetic Resonance in Medicine. © 2017 International Society for Magnetic Resonance in Medicine.

High-resolution small field-of-view magnetic resonance image acquisition system using a small planar coil and a pneumatic manipulator in an open MRI scanner.

PubMed

Miki, Kohei; Masamune, Ken

2015-10-01

Low-field open magnetic resonance imaging (MRI) is frequently used for performing image-guided neurosurgical procedures. Intraoperative magnetic resonance (MR) images are useful for tracking brain shifts and verifying residual tumors. However, it is difficult to precisely determine the boundary of the brain tumors and normal brain tissues because the MR image resolution is low, especially when using a low-field open MRI scanner. To overcome this problem, a high-resolution MR image acquisition system was developed and tested. An MR-compatible manipulator with pneumatic actuators containing an MR signal receiver with a small radiofrequency (RF) coil was developed. The manipulator had five degrees of freedom for position and orientation control of the RF coil. An 8-mm planar RF coil with resistance and inductance of 2.04 [Formula: see text] and 1.00 [Formula: see text] was attached to the MR signal receiver at the distal end of the probe. MR images of phantom test devices were acquired using the MR signal receiver and normal head coil for signal-to-noise ratio (SNR) testing. The SNR of MR images acquired using the MR signal receiver was 8.0 times greater than that of MR images acquired using the normal head coil. The RF coil was moved by the manipulator, and local MR images of a phantom with a 2-mm grid were acquired using the MR signal receiver. A wide field-of-view MR image was generated from a montage of local MR images. A small field-of-view RF system with a pneumatic manipulator was integrated in a low-field MRI scanner to allow acquisition of both wide field-of-view and high-resolution MR images. This system is promising for image-guided neurosurgery as it may allow brain tumors to be observed more clearly and removed precisely.

Visual brain activity patterns classification with simultaneous EEG-fMRI: A multimodal approach.

PubMed

Ahmad, Rana Fayyaz; Malik, Aamir Saeed; Kamel, Nidal; Reza, Faruque; Amin, Hafeez Ullah; Hussain, Muhammad

2017-01-01

Classification of the visual information from the brain activity data is a challenging task. Many studies reported in the literature are based on the brain activity patterns using either fMRI or EEG/MEG only. EEG and fMRI considered as two complementary neuroimaging modalities in terms of their temporal and spatial resolution to map the brain activity. For getting a high spatial and temporal resolution of the brain at the same time, simultaneous EEG-fMRI seems to be fruitful. In this article, we propose a new method based on simultaneous EEG-fMRI data and machine learning approach to classify the visual brain activity patterns. We acquired EEG-fMRI data simultaneously on the ten healthy human participants by showing them visual stimuli. Data fusion approach is used to merge EEG and fMRI data. Machine learning classifier is used for the classification purposes. Results showed that superior classification performance has been achieved with simultaneous EEG-fMRI data as compared to the EEG and fMRI data standalone. This shows that multimodal approach improved the classification accuracy results as compared with other approaches reported in the literature. The proposed simultaneous EEG-fMRI approach for classifying the brain activity patterns can be helpful to predict or fully decode the brain activity patterns.

Reduction in menopause-related symptoms associated with use of a noninvasive neurotechnology for autocalibration of neural oscillations.

PubMed

Tegeler, Charles H; Tegeler, Catherine L; Cook, Jared F; Lee, Sung W; Pajewski, Nicholas M

2015-06-01

Increased amplitudes in high-frequency brain electrical activity are reported with menopausal hot flashes. We report outcomes associated with the use of High-resolution, relational, resonance-based, electroencephalic mirroring--a noninvasive neurotechnology for autocalibration of neural oscillations--by women with perimenopausal and postmenopausal hot flashes. Twelve women with hot flashes (median age, 56 y; range, 46-69 y) underwent a median of 13 (range, 8-23) intervention sessions for a median of 9.5 days (range, 4-32). This intervention uses algorithmic analysis of brain electrical activity and near real-time translation of brain frequencies into variable tones for acoustic stimulation. Hot flash frequency and severity were recorded by daily diary. Primary outcomes included hot flash severity score, sleep, and depressive symptoms. High-frequency amplitudes (23-36 Hz) from bilateral temporal scalp recordings were measured at baseline and during serial sessions. Self-reported symptom inventories for sleep and depressive symptoms were collected. The median change in hot flash severity score was -0.97 (range, -3.00 to 1.00; P = 0.015). Sleep and depression scores decreased by -8.5 points (range, -20 to -1; P = 0.022) and -5.5 points (range, -32 to 8; P = 0.015), respectively. The median sum of amplitudes for the right and left temporal high-frequency brain electrical activity was 8.44 μV (range, 6.27-16.66) at baseline and decreased by a median of -2.96 μV (range, -11.05 to -0.65; P = 0.0005) by the final session. Hot flash frequency and severity, symptoms of insomnia and depression, and temporal high-frequency brain electrical activity decrease after High-resolution, relational, resonance-based, electroencephalic mirroring. Larger controlled trials with longer follow-up are warranted.

An Update of the Classical and Novel Methods Used for Measuring Fast Neurotransmitters During Normal and Brain Altered Function

PubMed Central

Cifuentes Castro, Victor Hugo; López Valenzuela, Carmen Lucía; Salazar Sánchez, Juan Carlos; Peña, Kenia Pardo; López Pérez, Silvia J.; Ibarra, Jorge Ortega; Villagrán, Alberto Morales

2014-01-01

To understand better the cerebral functions, several methods have been developed to study the brain activity, they could be related with morphological, electrophysiological, molecular and neurochemical techniques. Monitoring neurotransmitter concentration is a key role to know better how the brain works during normal or pathological conditions, as well as for studying the changes in neurotransmitter concentration with the use of several drugs that could affect or reestablish the normal brain activity. Immediate response of the brain to environmental conditions is related with the release of the fast acting neurotransmission by glutamate (Glu), γ-aminobutyric acid (GABA) and acetylcholine (ACh) through the opening of ligand-operated ion channels. Neurotransmitter release is mainly determined by the classical microdialysis technique, this is generally coupled to high performance liquid chromatography (HPLC). Detection of neurotransmitters can be done by fluorescence, optical density, electrochemistry or other detection systems more sophisticated. Although the microdialysis method is the golden technique to monitor the brain neurotransmitters, it has a poor temporal resolution. Recently, with the use of biosensor the drawback of temporal resolution has been improved considerably, however other inconveniences have merged, such as stability, reproducibility and the lack of reliable biosensors mainly for GABA. The aim of this review is to show the important advances in the different ways to measure neurotransmitter concentrations; both with the use of classic techniques as well as with the novel methods and alternant approaches to improve the temporal resolution. PMID:25977677

Abnormal hemodynamic response to forepaw stimulation in rat brain after cocaine injection

NASA Astrophysics Data System (ADS)

Chen, Wei; Park, Kicheon; Choi, Jeonghun; Pan, Yingtian; Du, Congwu

2015-03-01

Simultaneous measurement of hemodynamics is of great importance to evaluate the brain functional changes induced by brain diseases such as drug addiction. Previously, we developed a multimodal-imaging platform (OFI) which combined laser speckle contrast imaging with multi-wavelength imaging to simultaneously characterize the changes in cerebral blood flow (CBF), oxygenated- and deoxygenated- hemoglobin (HbO and HbR) from animal brain. Recently, we upgraded our OFI system that enables detection of hemodynamic changes in response to forepaw electrical stimulation to study potential brain activity changes elicited by cocaine. The improvement includes 1) high sensitivity to detect the cortical response to single forepaw electrical stimulation; 2) high temporal resolution (i.e., 16Hz/channel) to resolve dynamic variations in drug-delivery study; 3) high spatial resolution to separate the stimulation-evoked hemodynamic changes in vascular compartments from those in tissue. The system was validated by imaging the hemodynamic responses to the forepaw-stimulations in the somatosensory cortex of cocaine-treated rats. The stimulations and acquisitions were conducted every 2min over 40min, i.e., from 10min before (baseline) to 30min after cocaine challenge. Our results show that the HbO response decreased first (at ~4min) followed by the decrease of HbR response (at ~6min) after cocaine, and both did not fully recovered for over 30min. Interestingly, while CBF decreased at 4min, it partially recovered at 18min after cocaine administration. The results indicate the heterogeneity of cocaine's effects on vasculature and tissue metabolism, demonstrating the unique capability of optical imaging for brain functional studies.

Quantitative imaging of magnesium distribution at single-cell resolution in brain tumors and infiltrating tumor cells with secondary ion mass spectrometry (SIMS)

PubMed Central

Chandra, Subhash; Parker, Dylan J.; Barth, Rolf F.; Pannullo, Susan C.

2016-01-01

Glioblastoma multiforme (GBM) is one of the deadliest forms of human brain tumors. The infiltrative pattern of growth of these tumors includes the spread of individual and/or clusters of tumor cells at some distance from the main tumor mass in parts of the brain protected by an intact blood-brain-barrier. Pathophysiological studies of GBM could be greatly enhanced by analytical techniques capable of in situ single-cell resolution measurements of infiltrating tumor cells. Magnesium homeostasis is an area of active investigation in high grade gliomas. In the present study, we have used the F98 rat glioma as a model of human GBM and an elemental/isotopic imaging technique of secondary ion mass spectrometry (SIMS), a CAMECA IMS-3f ion microscope, for studying Mg distributions with single-cell resolution in freeze-dried brain tissue cryosections. Quantitative observations were made on tumor cells in the main tumor mass, contiguous brain tissue, and infiltrating tumor cells in adjacent normal brain. The brain tissue contained a significantly lower total Mg concentration of 4.70 ± 0.93 mmol/Kg wet weight (mean ± SD) in comparison to 11.64 ± 1.96 mmol/Kg wet weight in tumor cells of the main tumor mass and 10.72 ± 1.76 mmol/Kg wet weight in infiltrating tumor cells (p<0.05). The nucleus of individual tumor cells contained elevated levels of bound Mg. These observations demonstrate enhanced Mg-influx and increased binding of Mg in tumor cells and provide strong support for further investigation of GBMs for altered Mg homeostasis and activation of Mg-transporting channels as possible therapeutic targets. PMID:26703785

Silicon chip with capacitors and transistors for interfacing organotypic brain slice of rat hippocampus.

PubMed

Hutzler, Michael; Fromherz, Peter

2004-04-01

Probing projections between brain areas and their modulation by synaptic potentiation requires dense arrays of contacts for noninvasive electrical stimulation and recording. Semiconductor technology is able to provide planar arrays with high spatial resolution to be used with planar neuronal structures such as organotypic brain slices. To address basic methodical issues we developed a silicon chip with simple arrays of insulated capacitors and field-effect transistors for stimulation of neuronal activity and recording of evoked field potentials. Brain slices from rat hippocampus were cultured on that substrate. We achieved local stimulation of the CA3 region by applying defined voltage pulses to the chip capacitors. Recording of resulting local field potentials in the CA1 region was accomplished with transistors. The relationship between stimulation and recording was rationalized by a sheet conductor model. By combining a row of capacitors with a row of transistors we determined a simple stimulus-response matrix from CA3 to CA1. Possible contributions of inhomogeneities of synaptic projection, of tissue structure and of neuroelectronic interfacing were considered. The study provides the basis for a development of semiconductor chips with high spatial resolution that are required for long-term studies of topographic mapping.

Spontaneous rapid reduction of a large acute subdural hematoma.

PubMed

Lee, Chul-Hee; Kang, Dong Ho; Hwang, Soo Hyun; Park, In Sung; Jung, Jin-Myung; Han, Jong Woo

2009-12-01

The majority of acute post-traumatic subdural hematomas (ASDH) require urgent surgical evacuation. Spontaneous resolution of ASDH has been reported in some cases. We report here on a case of a patient with a large amount of ASDH that was rapidly reduced. A 61-yr-old man was found unconscious following a high speed motor vehicle accident. On initial examination, his Glasgow Coma Score scale was 4/15. His pupils were fully dilated and non-reactive to bright light. Brain computed tomography (CT) showed a massive right-sided ASDH. The decision was made to treat him conservatively because of his poor clinical condition. Another brain CT approximately 14 hr after the initial scan demonstrated a remarkable reduction of the previous ASDH and there was the new appearance of high density in the subdural space adjacent to the falx and the tentorium. Thirty days after his admission, brain CT revealed chronic SDH and the patient underwent surgery. The patient is currently able to obey simple commands. In conclusion, spontaneous rapid resolution/reduction of ASDH may occur in some patients. The mechanisms are most likely the result of dilution by cerebrospinal fluid and the redistribution of hematoma especially in patients with brain atrophy.

Spontaneous Rapid Reduction of a Large Acute Subdural Hematoma

PubMed Central

Kang, Dong Ho; Hwang, Soo Hyun; Park, In Sung; Jung, Jin-Myung; Han, Jong Woo

2009-01-01

The majority of acute post-traumatic subdural hematomas (ASDH) require urgent surgical evacuation. Spontaneous resolution of ASDH has been reported in some cases. We report here on a case of a patient with a large amount of ASDH that was rapidly reduced. A 61-yr-old man was found unconscious following a high speed motor vehicle accident. On initial examination, his Glasgow Coma Score scale was 4/15. His pupils were fully dilated and non-reactive to bright light. Brain computed tomography (CT) showed a massive right-sided ASDH. The decision was made to treat him conservatively because of his poor clinical condition. Another brain CT approximately 14 hr after the initial scan demonstrated a remarkable reduction of the previous ASDH and there was the new appearance of high density in the subdural space adjacent to the falx and the tentorium. Thirty days after his admission, brain CT revealed chronic SDH and the patient underwent surgery. The patient is currently able to obey simple commands. In conclusion, spontaneous rapid resolution/reduction of ASDH may occur in some patients. The mechanisms are most likely the result of dilution by cerebrospinal fluid and the redistribution of hematoma especially in patients with brain atrophy. PMID:19949689

Brain morphology in older African Americans, Caribbean Hispanics, and whites from northern Manhattan.

PubMed

Brickman, Adam M; Schupf, Nicole; Manly, Jennifer J; Luchsinger, José A; Andrews, Howard; Tang, Ming X; Reitz, Christiane; Small, Scott A; Mayeux, Richard; DeCarli, Charles; Brown, Truman R

2008-08-01

Aging is accompanied by a decrease in brain volume and by an increase in cerebrovascular disease. To examine the effects of age, sex, race/ethnicity, and vascular disease history on measures of brain morphology, including relative brain volume, ventricular volume, hippocampus and entorhinal cortex volumes, and white matter hyperintensity (WMH) burden, in a large community-based cohort of racially/ethnically diverse older adults without dementia. The associations of age, sex, race/ethnicity, and self-reported vascular disease history with brain morphology were examined in a cross-sectional study using multiple linear regression analyses. Sex x race/ethnicity interactions were also considered. The Washington Heights-Inwood Columbia Aging Project, a community-based epidemiological study of older adults from 3 racial/ethnic groups (white, Hispanic, and African American) from northern Manhattan. Beginning in 2003, high-resolution quantitative magnetic resonance (MR) images were acquired in 769 participants without dementia. Relative brain volume (total brain volume/intracranial volume), ventricular volume, and hippocampus and entorhinal cortex volumes were derived manually on high-resolution MR images. White matter hyperintensities were quantified semiautomatically on fluid-attenuated inversion recovery-T2-weighted MR images. Older age was associated with decreased relative brain volume and with increased ventricular and WMH volumes. Hispanic and African American participants had larger relative brain volumes and more severe WMH burden than white participants, but the associations of these variables with age were similar across racial/ethnic groups. Compared with men, women had larger relative brain volumes. Vascular disease was associated with smaller relative brain volume and with higher WMH burden, particularly among African Americans. Older age and vascular disease, particularly among African Americans, are associated with increased brain atrophy and WMH burden. African American and Hispanic subjects have larger relative brain volumes and more WMH than white subjects. Racial/ethnic group differences in WMH severity seem to be partially attributable to differences in vascular disease. Future work will focus on the determinants and cognitive correlates of these differences.

A three-dimensional single-cell-resolution whole-brain atlas using CUBIC-X expansion microscopy and tissue clearing.

PubMed

Murakami, Tatsuya C; Mano, Tomoyuki; Saikawa, Shu; Horiguchi, Shuhei A; Shigeta, Daichi; Baba, Kousuke; Sekiya, Hiroshi; Shimizu, Yoshihiro; Tanaka, Kenji F; Kiyonari, Hiroshi; Iino, Masamitsu; Mochizuki, Hideki; Tainaka, Kazuki; Ueda, Hiroki R

2018-04-01

A three-dimensional single-cell-resolution mammalian brain atlas will accelerate systems-level identification and analysis of cellular circuits underlying various brain functions. However, its construction requires efficient subcellular-resolution imaging throughout the entire brain. To address this challenge, we developed a fluorescent-protein-compatible, whole-organ clearing and homogeneous expansion protocol based on an aqueous chemical solution (CUBIC-X). The expanded, well-cleared brain enabled us to construct a point-based mouse brain atlas with single-cell annotation (CUBIC-Atlas). CUBIC-Atlas reflects inhomogeneous whole-brain development, revealing a significant decrease in the cerebral visual and somatosensory cortical areas during postnatal development. Probabilistic activity mapping of pharmacologically stimulated Arc-dVenus reporter mouse brains onto CUBIC-Atlas revealed the existence of distinct functional structures in the hippocampal dentate gyrus. CUBIC-Atlas is shareable by an open-source web-based viewer, providing a new platform for whole-brain cell profiling.

Functional connectivity in the mouse brain imaged by B-mode photoacoustic microscopy

NASA Astrophysics Data System (ADS)

Nasiriavanaki, Mohammadreza; Xing, Wenxin; Xia, Jun; Wang, Lihong V.

2014-03-01

The increasing use of mouse models for human brain disease studies, coupled with the fact that existing functional imaging modalities cannot be easily applied to mice, presents an emerging need for a new functional imaging modality. Utilizing acoustic-resolution photoacoustic microscopy (AR-PAM), we imaged spontaneous cerebral hemodynamic fluctuations and their associated functional connections in the mouse brain. The images were acquired noninvasively in B-scan mode with a fast frame rate, a large field of view, and a high spatial resolution. At a location relative to the bregma 0, correlations were investigated inter-hemispherically between bilaterally homologous regions, as well as intra-hemispherically within the same functional regions. The functional connectivity in different functional regions was studied. The locations of these regions agreed well with the Paxinos mouse brain atlas. The functional connectivity map obtained in this study can then be used in the investigation of brain disorders such as stroke, Alzheimer's, schizophrenia, multiple sclerosis, autism, and epilepsy. Our experiments show that photoacoustic microscopy is capable to detect connectivities between different functional regions in B-scan mode, promising a powerful functional imaging modality for future brain research.

Analysis of multiple quaternary ammonium compounds in the brain using tandem capillary column separation and high resolution mass spectrometric detection.

PubMed

Falasca, Sara; Petruzziello, Filomena; Kretz, Robert; Rainer, Gregor; Zhang, Xiaozhe

2012-06-08

Endogenous quaternary ammonium compounds are involved in various physiological processes in the central nervous system. In the present study, eleven quaternary ammonium compounds, including acetylcholine, choline, carnitine, acetylcarnitine and seven other acylcarnitines of low polarity, were analyzed from brain extracts using a two dimension capillary liquid chromatography-Fourier transform mass spectrometry method. To deal with their large difference in hydrophobicities, tandem coupling between reversed phase and hydrophilic interaction chromatography columns was used to separate all the targeted quaternary ammonium compounds. Using high accuracy mass spectrometry in selected ion monitoring mode, all the compounds could be detected from each brain sample with high selectivity. The developed method was applied for the relative quantification of these quaternary ammonium compounds in three different brain regions of tree shrews: prefrontal cortex, striatum, and hippocampus. The comparative analysis showed that quaternary ammonium compounds were differentially distributed across the three brain areas. The analytical method proved to be highly sensitive and reliable for simultaneous determination of all the targeted analytes from brain samples. Copyright © 2012 Elsevier B.V. All rights reserved.

TH-A-BRF-09: Integration of High-Resolution MRSI Into Glioblastoma Treatment Planning

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schreibmann, E; Cordova, J; Shu, H

2014-06-15

Purpose: Identification of a metabolite signature that shows significant tumor cell infiltration into normal brain in regions that do not appear abnormal on standard MRI scans would be extremely useful for radiation oncologists to choose optimal regions of brain to treat, and to quantify response beyond the MacDonald criteria. We report on integration of high-resolution magnetic resonance spectroscopic imaging (HR-MRSI) with radiation dose escalation treatment planning to define and target regions at high risk for recurrence. Methods: We propose to supplement standard MRI with a special technique performed on an MRI scanner to measure the metabolite levels within defined volumes.more » Metabolite imaging was acquired using an advanced MRSI technique combining 3D echo-planar spectroscopic imaging (EPSI) with parallel acquisition (GRAPPA) using a multichannel head coil that allows acquisition of whole brain metabolite maps with 108 μl resolution in 12 minutes implemented on a 3T MR scanner. Elevation in the ratio of two metabolites, choline (Cho, elevated in proliferating high-grade gliomas) and N-acetyl aspartate (NAA, a normal neuronal metabolite), was used to image infiltrating high-grade glioma cells in vivo. Results: The metabolite images were co-registered with standard contrast-enhanced T1-weighted MR images using in-house registration software and imported into the treatment-planning system. Regions with tumor infiltration are identified on the metabolic images and used to create adaptive IMRT plans that deliver a standard dose of 60 Gy to the standard target volume and an escalated dose of 75 Gy (or higher) to the most suspicious regions, identified as areas with elevated Cho/NAA ratio. Conclusion: We have implemented a state-of-the-art HR-MRSI technology that can generate metabolite maps of the entire brain in a clinically acceptable scan time, coupled with introduction of an imaging co-registration/ analysis program that combines MRSI data with standard imaging studies in a clinically useful fashion.« less

Electroencephalographic imaging of higher brain function

NASA Technical Reports Server (NTRS)

Gevins, A.; Smith, M. E.; McEvoy, L. K.; Leong, H.; Le, J.

1999-01-01

High temporal resolution is necessary to resolve the rapidly changing patterns of brain activity that underlie mental function. Electroencephalography (EEG) provides temporal resolution in the millisecond range. However, traditional EEG technology and practice provide insufficient spatial detail to identify relationships between brain electrical events and structures and functions visualized by magnetic resonance imaging or positron emission tomography. Recent advances help to overcome this problem by recording EEGs from more electrodes, by registering EEG data with anatomical images, and by correcting the distortion caused by volume conduction of EEG signals through the skull and scalp. In addition, statistical measurements of sub-second interdependences between EEG time-series recorded from different locations can help to generate hypotheses about the instantaneous functional networks that form between different cortical regions during perception, thought and action. Example applications are presented from studies of language, attention and working memory. Along with its unique ability to monitor brain function as people perform everyday activities in the real world, these advances make modern EEG an invaluable complement to other functional neuroimaging modalities.

Computation of Surface Laplacian for tri-polar ring electrodes on high-density realistic geometry head model.

PubMed

Junwei Ma; Han Yuan; Sunderam, Sridhar; Besio, Walter; Lei Ding

2017-07-01

Neural activity inside the human brain generate electrical signals that can be detected on the scalp. Electroencephalograph (EEG) is one of the most widely utilized techniques helping physicians and researchers to diagnose and understand various brain diseases. Due to its nature, EEG signals have very high temporal resolution but poor spatial resolution. To achieve higher spatial resolution, a novel tri-polar concentric ring electrode (TCRE) has been developed to directly measure Surface Laplacian (SL). The objective of the present study is to accurately calculate SL for TCRE based on a realistic geometry head model. A locally dense mesh was proposed to represent the head surface, where the local dense parts were to match the small structural components in TCRE. Other areas without dense mesh were used for the purpose of reducing computational load. We conducted computer simulations to evaluate the performance of the proposed mesh and evaluated possible numerical errors as compared with a low-density model. Finally, with achieved accuracy, we presented the computed forward lead field of SL for TCRE for the first time in a realistic geometry head model and demonstrated that it has better spatial resolution than computed SL from classic EEG recordings.

Phased Array 3D MR Spectroscopic Imaging of the Brain at 7 Tesla

PubMed Central

Xu, Duan; Cunningham, Charles H; Chen, Albert P.; Li, Yan; Kelley, Douglas AC; Mukherjee, Pratik; Pauly, John M.; Nelson, Sarah J.; Vigneron, Daniel B.

2008-01-01

Ultrahigh field 7T MR scanners offer the potential for greatly improved MR spectroscopic imaging due to increased sensitivity and spectral resolution. Prior 7T human single-voxel MRS studies have shown significant increases in SNR and spectral resolution as compared to lower magnetic fields, but have not demonstrated the increase in spatial resolution and multivoxel coverage possible with 7T MR spectroscopic imaging. The goal of this study was to develop specialized rf pulses and sequences for 3D MRSI at 7T to address the challenges of increased chemical shift misregistration, B1 power limitations, and increased spectral bandwidth. The new 7T MRSI sequence was tested in volunteer studies and demonstrated the feasibility of obtaining high SNR phased-array 3D MRSI from the human brain. PMID:18486386

Non-invasive high-resolution tracking of human neuronal pathways: diffusion tensor imaging at 7T with 1.2 mm isotropic voxel size

NASA Astrophysics Data System (ADS)

Lützkendorf, Ralf; Hertel, Frank; Heidemann, Robin; Thiel, Andreas; Luchtmann, Michael; Plaumann, Markus; Stadler, Jörg; Baecke, Sebastian; Bernarding, Johannes

2013-03-01

Diffusion tensor imaging (DTI) allows characterizing and exploiting diffusion anisotropy effects, thereby providing important details about tissue microstructure. A major application in neuroimaging is the so-called fiber tracking where neuronal connections between brain regions are determined non-invasively by DTI. Combining these neural pathways within the human brain with the localization of activated brain areas provided by functional MRI offers important information about functional connectivity of brain regions. However, DTI suffers from severe signal reduction due to the diffusion-weighting. Ultra-high field (UHF) magnetic resonance imaging (MRI) should therefore be advantageous to increase the intrinsic signal-to-noise ratio (SNR). This in turn enables to acquire high quality data with increased resolution, which is beneficial for tracking more complex fiber structures. However, UHF MRI imposes some difficulties mainly due to the larger B1 inhomogeneity compared to 3T MRI. We therefore optimized the parameters to perform DTI at a 7 Tesla whole body MR scanner equipped with a high performance gradient system and a 32-channel head receive coil. A Stesjkal Tanner spin-echo EPI sequence was used, to acquire 110 slices with an isotropic voxel-size of 1.2 mm covering the whole brain. 60 diffusion directions were scanned which allows calculating the principal direction components of the diffusion vector in each voxel. The results prove that DTI can be performed with high quality at UHF and that it is possible to explore the SNT benefit of the higher field strength. Combining UHF fMRI data with UHF DTI results will therefore be a major step towards better neuroimaging methods.

IMART software for correction of motion artifacts in images collected in intravital microscopy

PubMed Central

Dunn, Kenneth W; Lorenz, Kevin S; Salama, Paul; Delp, Edward J

2014-01-01

Intravital microscopy is a uniquely powerful tool, providing the ability to characterize cell and organ physiology in the natural context of the intact, living animal. With the recent development of high-resolution microscopy techniques such as confocal and multiphoton microscopy, intravital microscopy can now characterize structures at subcellular resolution and capture events at sub-second temporal resolution. However, realizing the potential for high resolution requires remarkable stability in the tissue. Whereas the rigid structure of the skull facilitates high-resolution imaging of the brain, organs of the viscera are free to move with respiration and heartbeat, requiring additional apparatus for immobilization. In our experience, these methods are variably effective, so that many studies are compromised by residual motion artifacts. Here we demonstrate the use of IMART, a software tool for removing motion artifacts from intravital microscopy images collected in time series or in three dimensions. PMID:26090271

A Prototype High-Resolution Small-Animal PET Scanner Dedicated to Mouse Brain Imaging.

PubMed

Yang, Yongfeng; Bec, Julien; Zhou, Jian; Zhang, Mengxi; Judenhofer, Martin S; Bai, Xiaowei; Di, Kun; Wu, Yibao; Rodriguez, Mercedes; Dokhale, Purushottam; Shah, Kanai S; Farrell, Richard; Qi, Jinyi; Cherry, Simon R

2016-07-01

We developed a prototype small-animal PET scanner based on depth-encoding detectors using dual-ended readout of small scintillator elements to produce high and uniform spatial resolution suitable for imaging the mouse brain. The scanner consists of 16 tapered dual-ended-readout detectors arranged in a 61-mm-diameter ring. The axial field of view (FOV) is 7 mm, and the transaxial FOV is 30 mm. The scintillator arrays consist of 14 × 14 lutetium oxyorthosilicate elements, with a crystal size of 0.43 × 0.43 mm at the front end and 0.80 × 0.43 mm at the back end, and the crystal elements are 13 mm long. The arrays are read out by 8 × 8 mm and 13 × 8 mm position-sensitive avalanche photodiodes (PSAPDs) placed at opposite ends of the array. Standard nuclear-instrumentation-module electronics and a custom-designed multiplexer are used for signal processing. The detector performance was measured, and all but the crystals at the very edge could be clearly resolved. The average intrinsic spatial resolution in the axial direction was 0.61 mm. A depth-of-interaction resolution of 1.7 mm was achieved. The sensitivity of the scanner at the center of the FOV was 1.02% for a lower energy threshold of 150 keV and 0.68% for a lower energy threshold of 250 keV. The spatial resolution within a FOV that can accommodate the entire mouse brain was approximately 0.6 mm using a 3-dimensional maximum-likelihood expectation maximization reconstruction. Images of a hot-rod microphantom showed that rods with a diameter of as low as 0.5 mm could be resolved. The first in vivo studies were performed using (18)F-fluoride and confirmed that a 0.6-mm resolution can be achieved in the mouse head in vivo. Brain imaging studies with (18)F-FDG were also performed. We developed a prototype PET scanner that can achieve a spatial resolution approaching the physical limits of a small-bore PET scanner set by positron range and detector interaction. We plan to add more detector rings to extend the axial FOV of the scanner and increase sensitivity. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

A high resolution prototype small-animal PET scanner dedicated to mouse brain imaging

PubMed Central

Yang, Yongfeng; Bec, Julien; Zhou, Jian; Zhang, Mengxi; Judenhofer, Martin S; Bai, Xiaowei; Di, Kun; Wu, Yibao; Rodriguez, Mercedes; Dokhale, Purushottam; Shah, Kanai S.; Farrell, Richard; Qi, Jinyi; Cherry, Simon R.

2017-01-01

A prototype small-animal PET scanner was developed based on depth-encoding detectors using dual-ended readout of very small scintillator elements to produce high and uniform spatial resolution suitable for imaging the mouse brain. Methods The scanner consists of 16 tapered dual-ended readout detectors arranged in a ring of diameter 61 mm. The axial field of view is 7 mm and the transaxial field of view is 30 mm. The scintillator arrays consist of 14×14 lutetium oxyorthosilicate (LSO) elements, with a crystal size of 0.43×0.43 mm2 at the front end and 0.80×0.43 mm2 at the back end, and the crystal elements are 13 mm long. The arrays are read out by 8×8 mm2 and a 13×8 mm2 position-sensitive avalanche photodiodes (PSAPDs) placed at opposite ends of the array. Standard nuclear instrumentation module (NIM) electronics and a custom designed multiplexer are used for signal processing. Results The detector performance was measured and all except the very edge crystals could be clearly resolved. The average detector intrinsic spatial resolution in the axial direction was 0.61 mm. A depth of interaction resolution of 1.7 mm was achieved. The sensitivity of the scanner at center of the field of view was 1.02% for a lower energy threshold of 150 keV and 0.68% for a lower energy threshold of 250 keV. The spatial resolution within a field of view that can accommodate the entire mouse brain was ~0.6 mm using a 3D Maximum Likelihood-Expectation Maximization (ML-EM) reconstruction algorithm. Images of a micro hot-rod phantom showed that rods with diameter down to 0.5 mm could be resolved. First in vivo studies were obtained using 18F-fluoride and confirmed that 0.6 mm resolution can be achieved in the mouse head in vivo. Brain imaging studies with 18F-fluorodeoxyglucose were also acquired. Conclusion A prototype PET scanner achieving a spatial resolution approaching the physical limits for a small-bore PET scanner set by positron range and acolinearity was developed. Future plans are to add more detector rings to extend the axial field of view of the scanner and increase sensitivity. PMID:27013696

BabySQUID: A mobile, high-resolution multichannel magnetoencephalography system for neonatal brain assessment

NASA Astrophysics Data System (ADS)

Okada, Yoshio; Pratt, Kevin; Atwood, Christopher; Mascarenas, Anthony; Reineman, Richard; Nurminen, Jussi; Paulson, Douglas

2006-02-01

We developed a prototype of a mobile, high-resolution, multichannel magnetoencephalography (MEG) system, called babySQUID, for assessing brain functions in newborns and infants. Unlike electroencephalography, MEG signals are not distorted by the scalp or the fontanels and sutures in the skull. Thus, brain activity can be measured and localized with MEG as if the sensors were above an exposed brain. The babySQUID is housed in a moveable cart small enough to be transported from one room to another. To assess brain functions, one places the baby on the bed of the cart and the head on its headrest with MEG sensors just below. The sensor array consists of 76 first-order axial gradiometers, each with a pickup coil diameter of 6mm and a baseline of 30mm, in a high-density array with a spacing of 12-14mm center-to-center. The pickup coils are 6±1mm below the outer surface of the headrest. The short gap provides unprecedented sensitivity since the scalp and skull are thin (as little as 3-4mm altogether) in babies. In an electromagnetically unshielded room in a hospital, the field sensitivity at 1kHz was ˜17fT/√Hz. The noise was reduced from ˜400to200fT/√Hz at 1Hz using a reference cancellation technique and further to ˜40fT/√Hz using a gradient common mode rejection technique. Although the residual environmental magnetic noise interfered with the operation of the babySQUID, the instrument functioned sufficiently well to detect spontaneous brain signals from babies with a signal to noise ratio (SNR) of as much as 7.6:1. In a magnetically shielded room, the field sensitivity was 17fT/√Hz at 20Hz and 30fT/√Hz at 1Hz without implementation of reference or gradient cancellation. The sensitivity was sufficiently high to detect spontaneous brain activity from a 7month old baby with a SNR as much as 40:1 and evoked somatosensory responses with a 50Hz bandwidth after as little as four averages. We expect that both the noise and the sensor gap can be reduced further by approximately half with a gain in SNR of about four. Thus, we conclude from the performance of the prototype that it should be feasible to improve the babySQUID to detect cortical activity in infants in real time with high spatial resolution.

Combined lineage mapping and gene expression profiling of embryonic brain patterning using ultrashort pulse microscopy and image registration

NASA Astrophysics Data System (ADS)

Gibbs, Holly C.; Dodson, Colin R.; Bai, Yuqiang; Lekven, Arne C.; Yeh, Alvin T.

2014-12-01

During embryogenesis, presumptive brain compartments are patterned by dynamic networks of gene expression. The spatiotemporal dynamics of these networks, however, have not been characterized with sufficient resolution for us to understand the regulatory logic resulting in morphogenetic cellular behaviors that give the brain its shape. We have developed a new, integrated approach using ultrashort pulse microscopy [a high-resolution, two-photon fluorescence (2PF)-optical coherence microscopy (OCM) platform using 10-fs pulses] and image registration to study brain patterning and morphogenesis in zebrafish embryos. As a demonstration, we used time-lapse 2PF to capture midbrain-hindbrain boundary morphogenesis and a wnt1 lineage map from embryos during brain segmentation. We then performed in situ hybridization to deposit NBT/BCIP, where wnt1 remained actively expressed, and reimaged the embryos with combined 2PF-OCM. When we merged these datasets using morphological landmark registration, we found that the mechanism of boundary formation differs along the dorsoventral axis. Dorsally, boundary sharpening is dominated by changes in gene expression, while ventrally, sharpening may be accomplished by lineage sorting. We conclude that the integrated visualization of lineage reporter and gene expression domains simultaneously with brain morphology will be useful for understanding how changes in gene expression give rise to proper brain compartmentalization and structure.

Combined lineage mapping and gene expression profiling of embryonic brain patterning using ultrashort pulse microscopy and image registration.

PubMed

Gibbs, Holly C; Dodson, Colin R; Bai, Yuqiang; Lekven, Arne C; Yeh, Alvin T

2014-12-01

During embryogenesis, presumptive brain compartments are patterned by dynamic networks of gene expression. The spatiotemporal dynamics of these networks, however, have not been characterized with sufficient resolution for us to understand the regulatory logic resulting in morphogenetic cellular behaviors that give the brain its shape. We have developed a new, integrated approach using ultrashort pulse microscopy [a high-resolution, two-photon fluorescence (2PF)-optical coherence microscopy (OCM) platform using 10-fs pulses] and image registration to study brain patterning and morphogenesis in zebrafish embryos. As a demonstration, we used time-lapse 2PF to capture midbrain-hindbrain boundary morphogenesis and a wnt1 lineage map from embryos during brain segmentation. We then performed in situ hybridization to deposit NBT/BCIP, where wnt1 remained actively expressed, and reimaged the embryos with combined 2PF-OCM. When we merged these datasets using morphological landmark registration, we found that the mechanism of boundary formation differs along the dorsoventral axis. Dorsally, boundary sharpening is dominated by changes in gene expression, while ventrally, sharpening may be accomplished by lineage sorting. We conclude that the integrated visualization of lineage reporter and gene expression domains simultaneously with brain morphology will be useful for understanding how changes in gene expression give rise to proper brain compartmentalization and structure.

Compressed sensing for high-resolution nonlipid suppressed 1 H FID MRSI of the human brain at 9.4T.

PubMed

Nassirpour, Sahar; Chang, Paul; Avdievitch, Nikolai; Henning, Anke

2018-04-29

The aim of this study was to apply compressed sensing to accelerate the acquisition of high resolution metabolite maps of the human brain using a nonlipid suppressed ultra-short TR and TE 1 H FID MRSI sequence at 9.4T. X-t sparse compressed sensing reconstruction was optimized for nonlipid suppressed 1 H FID MRSI data. Coil-by-coil x-t sparse reconstruction was compared with SENSE x-t sparse and low rank reconstruction. The effect of matrix size and spatial resolution on the achievable acceleration factor was studied. Finally, in vivo metabolite maps with different acceleration factors of 2, 4, 5, and 10 were acquired and compared. Coil-by-coil x-t sparse compressed sensing reconstruction was not able to reliably recover the nonlipid suppressed data, rather a combination of parallel and sparse reconstruction was necessary (SENSE x-t sparse). For acceleration factors of up to 5, both the low-rank and the compressed sensing methods were able to reconstruct the data comparably well (root mean squared errors [RMSEs] ≤ 10.5% for Cre). However, the reconstruction time of the low rank algorithm was drastically longer than compressed sensing. Using the optimized compressed sensing reconstruction, acceleration factors of 4 or 5 could be reached for the MRSI data with a matrix size of 64 × 64. For lower spatial resolutions, an acceleration factor of up to R∼4 was successfully achieved. By tailoring the reconstruction scheme to the nonlipid suppressed data through parameter optimization and performance evaluation, we present high resolution (97 µL voxel size) accelerated in vivo metabolite maps of the human brain acquired at 9.4T within scan times of 3 to 3.75 min. © 2018 International Society for Magnetic Resonance in Medicine.

Pig Brain Mitochondria as a Biological Model for Study of Mitochondrial Respiration.

PubMed

Fišar, Z; Hroudová, J

2016-01-01

Oxidative phosphorylation is a key process of intracellular energy transfer by which mitochondria produce ATP. Isolated mitochondria serve as a biological model for understanding the mitochondrial respiration control, effects of various biologically active substances, and pathophysiology of mitochondrial diseases. The aim of our study was to evaluate pig brain mitochondria as a proper biological model for investigation of activity of the mitochondrial electron transport chain. Oxygen consumption rates of isolated pig brain mitochondria were measured using high-resolution respirometry. Mitochondrial respiration of crude mitochondrial fraction, mitochondria purified in sucrose gradient, and mitochondria purified in Percoll gradient were assayed as a function of storage time. Oxygen flux and various mitochondrial respiratory control ratios were not changed within two days of mitochondria storage on ice. Leak respiration was found higher and Complex I-linked respiration lower in purified mitochondria compared to the crude mitochondrial fraction. Damage to both outer and inner mitochondrial membrane caused by the isolation procedure was the greatest after purification in a sucrose gradient. We confirmed that pig brain mitochondria can serve as a biological model for investigation of mitochondrial respiration. The advantage of this biological model is the stability of respiratory parameters for more than 48 h and the possibility to isolate large amounts of mitochondria from specific brain areas without the need to kill laboratory animals. We suggest the use of high-resolution respirometry of pig brain mitochondria for research of the neuroprotective effects and/or mitochondrial toxicity of new medical drugs.

Monte Carlo simulation studies on scintillation detectors and image reconstruction of brain-phantom tumors in TOFPET

PubMed Central

Mondal, Nagendra Nath

2009-01-01

This study presents Monte Carlo Simulation (MCS) results of detection efficiencies, spatial resolutions and resolving powers of a time-of-flight (TOF) PET detector systems. Cerium activated Lutetium Oxyorthosilicate (Lu2SiO5: Ce in short LSO), Barium Fluoride (BaF2) and BriLanCe 380 (Cerium doped Lanthanum tri-Bromide, in short LaBr3) scintillation crystals are studied in view of their good time and energy resolutions and shorter decay times. The results of MCS based on GEANT show that spatial resolution, detection efficiency and resolving power of LSO are better than those of BaF2 and LaBr3, although it possesses inferior time and energy resolutions. Instead of the conventional position reconstruction method, newly established image reconstruction (talked about in the previous work) method is applied to produce high-tech images. Validation is a momentous step to ensure that this imaging method fulfills all purposes of motivation discussed by reconstructing images of two tumors in a brain phantom. PMID:20098551

Designing a compact high performance brain PET scanner—simulation study

NASA Astrophysics Data System (ADS)

Gong, Kuang; Majewski, Stan; Kinahan, Paul E.; Harrison, Robert L.; Elston, Brian F.; Manjeshwar, Ravindra; Dolinsky, Sergei; Stolin, Alexander V.; Brefczynski-Lewis, Julie A.; Qi, Jinyi

2016-05-01

The desire to understand normal and disordered human brain function of upright, moving persons in natural environments motivates the development of the ambulatory micro-dose brain PET imager (AMPET). An ideal system would be light weight but with high sensitivity and spatial resolution, although these requirements are often in conflict with each other. One potential approach to meet the design goals is a compact brain-only imaging device with a head-sized aperture. However, a compact geometry increases parallax error in peripheral lines of response, which increases bias and variance in region of interest (ROI) quantification. Therefore, we performed simulation studies to search for the optimal system configuration and to evaluate the potential improvement in quantification performance over existing scanners. We used the Cramér-Rao variance bound to compare the performance for ROI quantification using different scanner geometries. The results show that while a smaller ring diameter can increase photon detection sensitivity and hence reduce the variance at the center of the field of view, it can also result in higher variance in peripheral regions when the length of detector crystal is 15 mm or more. This variance can be substantially reduced by adding depth-of-interaction (DOI) measurement capability to the detector modules. Our simulation study also shows that the relative performance depends on the size of the ROI, and a large ROI favors a compact geometry even without DOI information. Based on these results, we propose a compact ‘helmet’ design using detectors with DOI capability. Monte Carlo simulations show the helmet design can achieve four-fold higher sensitivity and resolve smaller features than existing cylindrical brain PET scanners. The simulations also suggest that improving TOF timing resolution from 400 ps to 200 ps also results in noticeable improvement in image quality, indicating better timing resolution is desirable for brain imaging.

Designing a compact high performance brain PET scanner—simulation study

PubMed Central

Gong, Kuang; Majewski, Stan; Kinahan, Paul E; Harrison, Robert L; Elston, Brian F; Manjeshwar, Ravindra; Dolinsky, Sergei; Stolin, Alexander V; Brefczynski-Lewis, Julie A; Qi, Jinyi

2016-01-01

The desire to understand normal and disordered human brain function of upright, moving persons in natural environments motivates the development of the ambulatory micro-dose brain PET imager (AMPET). An ideal system would be light weight but with high sensitivity and spatial resolution, although these requirements are often in conflict with each other. One potential approach to meet the design goals is a compact brain-only imaging device with a head-sized aperture. However, a compact geometry increases parallax error in peripheral lines of response, which increases bias and variance in region of interest (ROI) quantification. Therefore, we performed simulation studies to search for the optimal system configuration and to evaluate the potential improvement in quantification performance over existing scanners. We used the Cramér–Rao variance bound to compare the performance for ROI quantification using different scanner geometries. The results show that while a smaller ring diameter can increase photon detection sensitivity and hence reduce the variance at the center of the field of view, it can also result in higher variance in peripheral regions when the length of detector crystal is 15 mm or more. This variance can be substantially reduced by adding depth-of- interaction (DOI) measurement capability to the detector modules. Our simulation study also shows that the relative performance depends on the size of the ROI, and a large ROI favors a compact geometry even without DOI information. Based on these results, we propose a compact ‘helmet’ design using detectors with DOI capability. Monte Carlo simulations show the helmet design can achieve four-fold higher sensitivity and resolve smaller features than existing cylindrical brain PET scanners. The simulations also suggest that improving TOF timing resolution from 400 ps to 200 ps also results in noticeable improvement in image quality, indicating better timing resolution is desirable for brain imaging. PMID:27081753

DEVELOPMENT OF THE “RICH CLUB” IN BRAIN CONNECTIVITY NETWORKS FROM 438 ADOLESCENTS & ADULTS AGED 12 TO 30

PubMed Central

Dennis, Emily L.; Jahanshad, Neda; Toga, Arthur W.; McMahon, Katie L.; de Zubicaray, Greig I.; Hickie, Ian; Wright, Margaret J.; Thompson, Paul M.

2014-01-01

The ‘rich club’ coefficient describes a phenomenon where a network's hubs (high-degree nodes) are on average more intensely interconnected than lower-degree nodes. Networks with rich clubs often have an efficient, higher-order organization, but we do not yet know how the rich club emerges in the living brain, or how it changes as our brain networks develop. Here we chart the developmental trajectory of the rich club in anatomical brain networks from 438 subjects aged 12-30. Cortical networks were constructed from 68×68 connectivity matrices of fiber density, using whole-brain tractography in 4-Tesla 105-gradient high angular resolution diffusion images (HARDI). The adult and younger cohorts had rich clubs that included different nodes; the rich club effect intensified with age. Rich-club organization is a sign of a network's efficiency and robustness. These concepts and findings may be advantageous for studying brain maturation and abnormal brain development. PMID:24827471

A mass spectrometry imaging approach for investigating how drug-drug interactions influence drug blood-brain barrier permeability.

PubMed

Vallianatou, Theodosia; Strittmatter, Nicole; Nilsson, Anna; Shariatgorji, Mohammadreza; Hamm, Gregory; Pereira, Marcela; Källback, Patrik; Svenningsson, Per; Karlgren, Maria; Goodwin, Richard J A; Andrén, Per E

2018-05-15

There is a high need to develop quantitative imaging methods capable of providing detailed brain localization information of several molecular species simultaneously. In addition, extensive information on the effect of the blood-brain barrier on the penetration, distribution and efficacy of neuroactive compounds is required. Thus, we have developed a mass spectrometry imaging method to visualize and quantify the brain distribution of drugs with varying blood-brain barrier permeability. With this approach, we were able to determine blood-brain barrier transport of different drugs and define the drug distribution in very small brain structures (e.g., choroid plexus) due to the high spatial resolution provided. Simultaneously, we investigated the effect of drug-drug interactions by inhibiting the membrane transporter multidrug resistance 1 protein. We propose that the described approach can serve as a valuable analytical tool during the development of neuroactive drugs, as it can provide physiologically relevant information often neglected by traditional imaging technologies. Copyright © 2018. Published by Elsevier Inc.

HIV-1 Phylogenetic analysis shows HIV-1 transits through the meninges to brain and peripheral tissues

PubMed Central

Lamers, Susanna L.; Gray, Rebecca R.; Salemi, Marco; Huysentruyt, Leanne C.; McGrath, Michael

2010-01-01

Brain infection by the human immunodeficiency virus type 1 (HIV-1) has been investigated in many reports with a variety of conclusions concerning the time of entry and degree of viral compartmentalization. To address these diverse findings, we sequenced HIV-1 gp120 clones from a wide range of brain, peripheral and meningeal tissues from five patients who died from several HIV-1 associated disease pathologies. High-resolution phylogenetic analysis confirmed previous studies that showed a significant degree of compartmentalization in brain and peripheral tissue subpopulations. Some intermixing between the HIV-1 subpopulations was evident, especially in patients that died from pathologies other than HIV-associated dementia. Interestingly, the major tissue harboring virus from both the brain and peripheral tissues was the meninges. These results show that 1) HIV-1 is clearly capable of migrating out of the brain, 2) the meninges are the most likely primary transport tissues, and 3) infected brain macrophages comprise an important HIV reservoir during highly active antiretroviral therapy. PMID:21055482

Rapid anatomical brain imaging using spiral acquisition and an expanded signal model.

PubMed

Kasper, Lars; Engel, Maria; Barmet, Christoph; Haeberlin, Maximilian; Wilm, Bertram J; Dietrich, Benjamin E; Schmid, Thomas; Gross, Simon; Brunner, David O; Stephan, Klaas E; Pruessmann, Klaas P

2018-03-01

We report the deployment of spiral acquisition for high-resolution structural imaging at 7T. Long spiral readouts are rendered manageable by an expanded signal model including static off-resonance and B 0 dynamics along with k-space trajectories and coil sensitivity maps. Image reconstruction is accomplished by inversion of the signal model using an extension of the iterative non-Cartesian SENSE algorithm. Spiral readouts up to 25 ms are shown to permit whole-brain 2D imaging at 0.5 mm in-plane resolution in less than a minute. A range of options is explored, including proton-density and T 2 * contrast, acceleration by parallel imaging, different readout orientations, and the extraction of phase images. Results are shown to exhibit competitive image quality along with high geometric consistency. Copyright © 2017 Elsevier Inc. All rights reserved.

High-resolution in vivo Wistar rodent brain atlas based on T1 weighted image

NASA Astrophysics Data System (ADS)

Huang, Su; Lu, Zhongkang; Huang, Weimin; Seramani, Sankar; Ramasamy, Boominathan; Sekar, Sakthivel; Guan, Cuntai; Bhakoo, Kishore

2016-03-01

Image based atlases for rats brain have a significant impact on pre-clinical research. In this project we acquired T1-weighted images from Wistar rodent brains with fine 59μm isotropical resolution for generation of the atlas template image. By applying post-process procedures using a semi-automatic brain extraction method, we delineated the brain tissues from source data. Furthermore, we applied a symmetric group-wise normalization method to generate an optimized template of T1 image of rodent brain, then aligned our template to the Waxholm Space. In addition, we defined several simple and explicit landmarks to corresponding our template with the well known Paxinos stereotaxic reference system. Anchoring at the origin of the Waxholm Space, we applied piece-wise linear transformation method to map the voxels of the template into the coordinates system in Paxinos' stereotoxic coordinates to facilitate the labelling task. We also cross-referenced our data with both published rodent brain atlas and image atlases available online, methodologically labelling the template to produce a Wistar brain atlas identifying more than 130 structures. Particular attention was paid to the cortex and cerebellum, as these areas encompass the most researched aspects of brain functions. Moreover, we adopted the structure hierarchy and naming nomenclature common to various atlases, so that the names and hierarchy structure presented in the atlas are readily recognised for easy use. It is believed the atlas will present a useful tool in rodent brain functional and pharmaceutical studies.

A combined solenoid-surface RF coil for high-resolution whole-brain rat imaging on a 3.0 Tesla clinical MR scanner.

PubMed

Underhill, Hunter R; Yuan, Chun; Hayes, Cecil E

2010-09-01

Rat brain models effectively simulate a multitude of human neurological disorders. Improvements in coil design have facilitated the wider utilization of rat brain models by enabling the utilization of clinical MR scanners for image acquisition. In this study, a novel coil design, subsequently referred to as the rat brain coil, is described that exploits and combines the strengths of both solenoids and surface coils into a simple, multichannel, receive-only coil dedicated to whole-brain rat imaging on a 3.0 T clinical MR scanner. Compared with a multiturn solenoid mouse body coil, a 3-cm surface coil, a modified Helmholtz coil, and a phased-array surface coil, the rat brain coil improved signal-to-noise ratio by approximately 72, 61, 78, and 242%, respectively. Effects of the rat brain coil on amplitudes of static field and radiofrequency field uniformity were similar to each of the other coils. In vivo, whole-brain images of an adult male rat were acquired with a T(2)-weighted spin-echo sequence using an isotropic acquisition resolution of 0.25 x 0.25 x 0.25 mm(3) in 60.6 min. Multiplanar images of the in vivo rat brain with identification of anatomic structures are presented. Improvement in signal-to-noise ratio afforded by the rat brain coil may broaden experiments that utilize clinical MR scanners for in vivo image acquisition. 2010 Wiley-Liss, Inc.

Comprehensive optical and data management infrastructure for high-throughput light-sheet microscopy of whole mouse brains.

PubMed

Müllenbroich, M Caroline; Silvestri, Ludovico; Onofri, Leonardo; Costantini, Irene; Hoff, Marcel Van't; Sacconi, Leonardo; Iannello, Giulio; Pavone, Francesco S

2015-10-01

Comprehensive mapping and quantification of neuronal projections in the central nervous system requires high-throughput imaging of large volumes with microscopic resolution. To this end, we have developed a confocal light-sheet microscope that has been optimized for three-dimensional (3-D) imaging of structurally intact clarified whole-mount mouse brains. We describe the optical and electromechanical arrangement of the microscope and give details on the organization of the microscope management software. The software orchestrates all components of the microscope, coordinates critical timing and synchronization, and has been written in a versatile and modular structure using the LabVIEW language. It can easily be adapted and integrated to other microscope systems and has been made freely available to the light-sheet community. The tremendous amount of data routinely generated by light-sheet microscopy further requires novel strategies for data handling and storage. To complete the full imaging pipeline of our high-throughput microscope, we further elaborate on big data management from streaming of raw images up to stitching of 3-D datasets. The mesoscale neuroanatomy imaged at micron-scale resolution in those datasets allows characterization and quantification of neuronal projections in unsectioned mouse brains.

Annotation: What Electrical Brain Activity Tells Us about Brain Function that Other Techniques Cannot Tell Us--A Child Psychiatric Perspective

ERIC Educational Resources Information Center

Banaschewski, Tobias; Brandeis, Daniel

2007-01-01

Background: Monitoring brain processes in real time requires genuine subsecond resolution to follow the typical timing and frequency of neural events. Non-invasive recordings of electric (EEG/ERP) and magnetic (MEG) fields provide this time resolution. They directly measure neural activations associated with a wide variety of brain states and…

High axial resolution imaging system for large volume tissues using combination of inclined selective plane illumination and mechanical sectioning

PubMed Central

Zhang, Qi; Yang, Xiong; Hu, Qinglei; Bai, Ke; Yin, Fangfang; Li, Ning; Gang, Yadong; Wang, Xiaojun; Zeng, Shaoqun

2017-01-01

To resolve fine structures of biological systems like neurons, it is required to realize microscopic imaging with sufficient spatial resolution in three dimensional systems. With regular optical imaging systems, high lateral resolution is accessible while high axial resolution is hard to achieve in a large volume. We introduce an imaging system for high 3D resolution fluorescence imaging of large volume tissues. Selective plane illumination was adopted to provide high axial resolution. A scientific CMOS working in sub-array mode kept the imaging area in the sample surface, which restrained the adverse effect of aberrations caused by inclined illumination. Plastic embedding and precise mechanical sectioning extended the axial range and eliminated distortion during the whole imaging process. The combination of these techniques enabled 3D high resolution imaging of large tissues. Fluorescent bead imaging showed resolutions of 0.59 μm, 0.47μm, and 0.59 μm in the x, y, and z directions, respectively. Data acquired from the volume sample of brain tissue demonstrated the applicability of this imaging system. Imaging of different depths showed uniform performance where details could be recognized in either the near-soma area or terminal area, and fine structures of neurons could be seen in both the xy and xz sections. PMID:29296503

Brain functional BOLD perturbation modelling for forward fMRI and inverse mapping

PubMed Central

Robinson, Jennifer; Calhoun, Vince

2018-01-01

Purpose To computationally separate dynamic brain functional BOLD responses from static background in a brain functional activity for forward fMRI signal analysis and inverse mapping. Methods A brain functional activity is represented in terms of magnetic source by a perturbation model: χ = χ0 +δχ, with δχ for BOLD magnetic perturbations and χ0 for background. A brain fMRI experiment produces a timeseries of complex-valued images (T2* images), whereby we extract the BOLD phase signals (denoted by δP) by a complex division. By solving an inverse problem, we reconstruct the BOLD δχ dataset from the δP dataset, and the brain χ distribution from a (unwrapped) T2* phase image. Given a 4D dataset of task BOLD fMRI, we implement brain functional mapping by temporal correlation analysis. Results Through a high-field (7T) and high-resolution (0.5mm in plane) task fMRI experiment, we demonstrated in detail the BOLD perturbation model for fMRI phase signal separation (P + δP) and reconstructing intrinsic brain magnetic source (χ and δχ). We also provided to a low-field (3T) and low-resolution (2mm) task fMRI experiment in support of single-subject fMRI study. Our experiments show that the δχ-depicted functional map reveals bidirectional BOLD χ perturbations during the task performance. Conclusions The BOLD perturbation model allows us to separate fMRI phase signal (by complex division) and to perform inverse mapping for pure BOLD δχ reconstruction for intrinsic functional χ mapping. The full brain χ reconstruction (from unwrapped fMRI phase) provides a new brain tissue image that allows to scrutinize the brain tissue idiosyncrasy for the pure BOLD δχ response through an automatic function/structure co-localization. PMID:29351339

The effect of lead exposure on fatty acid composition in mouse brain analyzed using pseudo-catalytic derivatization.

PubMed

Jung, Jong-Min; Lee, Jechan; Kim, Ki-Hyun; Jang, In Geon; Song, Jae Gwang; Kang, Kyeongjin; Tack, Filip M G; Oh, Jeong-Ik; Kwon, Eilhann E; Kim, Hyung-Wook

2017-03-01

We performed toxicological study of mice exposed to lead by quantifying fatty acids in brain of the mice. This study suggests that the introduced analytical method had an extremely high tolerance against impurities such as water and extractives; thus, it led to the enhanced resolution in visualizing the spectrum of fatty acid profiles in animal brain. Furthermore, one of the biggest technical advantages achieved in this study was the quantitation of fatty acid methyl ester profiles of mouse brain using a trace amount of sample (e.g., 100 μL mixture). Methanol was screened as the most effective extraction solvent for mouse brain. The behavioral test of the mice before and after lead exposure was conducted to see the effect of lead exposure on fatty acid composition of the mice' brain. The lead exposure led to changes in disease-related behavior of the mice. Also, the lead exposure induced significant alterations of fatty acid profile (C16:0, C 18:0, and C 18:1) in brain of the mice, implicated in pathology of psychiatric diseases. The alteration of fatty acid profile of brain of the mice suggests that the derivatizing technique can be applicable to most research fields associated with the environmental neurotoxins with better resolution in a short time, as compared to the current protocols for lipid analysis. Copyright © 2016 Elsevier Ltd. All rights reserved.

Metabolomic signature of brain cancer.

PubMed

Pandey, Renu; Caflisch, Laura; Lodi, Alessia; Brenner, Andrew J; Tiziani, Stefano

2017-11-01

Despite advances in surgery and adjuvant therapy, brain tumors represent one of the leading causes of cancer-related mortality and morbidity in both adults and children. Gliomas constitute about 60% of all cerebral tumors, showing varying degrees of malignancy. They are difficult to treat due to dismal prognosis and limited therapeutics. Metabolomics is the untargeted and targeted analyses of endogenous and exogenous small molecules, which charact erizes the phenotype of an individual. This emerging "omics" science provides functional readouts of cellular activity that contribute greatly to the understanding of cancer biology including brain tumor biology. Metabolites are highly informative as a direct signature of biochemical activity; therefore, metabolite profiling has become a promising approach for clinical diagnostics and prognostics. The metabolic alterations are well-recognized as one of the key hallmarks in monitoring disease progression, therapy, and revealing new molecular targets for effective therapeutic intervention. Taking advantage of the latest high-throughput analytical technologies, that is, nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS), metabolomics is now a promising field for precision medicine and drug discovery. In the present report, we review the application of metabolomics and in vivo metabolic profiling in the context of adult gliomas and paediatric brain tumors. Analytical platforms such as high-resolution (HR) NMR, in vivo magnetic resonance spectroscopic imaging and high- and low-resolution MS are discussed. Moreover, the relevance of metabolic studies in the development of new therapeutic strategies for treatment of gliomas are reviewed. © 2017 Wiley Periodicals, Inc.

Regional gray matter density associated with emotional conflict resolution: evidence from voxel-based morphometry.

PubMed

Deng, Z; Wei, D; Xue, S; Du, X; Hitchman, G; Qiu, J

2014-09-05

Successful emotion regulation is a fundamental prerequisite for well-being and dysregulation may lead to psychopathology. The ability to inhibit spontaneous emotions while behaving in accordance with desired goals is an important dimension of emotion regulation and can be measured using emotional conflict resolution tasks. Few studies have investigated the gray matter correlates underlying successful emotional conflict resolution at the whole-brain level. We had 190 adults complete an emotional conflict resolution task (face-word task) and examined the brain regions significantly correlated with successful emotional conflict resolution using voxel-based morphometry. We found successful emotional conflict resolution was associated with increased regional gray matter density in widely distributed brain regions. These regions included the dorsal anterior cingulate/dorsal medial prefrontal cortex, ventral medial prefrontal cortex, supplementary motor area, amygdala, ventral striatum, precuneus, posterior cingulate cortex, inferior parietal lobule, superior temporal gyrus and fusiform face area. Together, our results indicate that individual differences in emotional conflict resolution ability may be attributed to regional structural differences across widely distributed brain regions. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

Towards High-Resolution Tissue Imaging Using Nanospray Desorption Electrospray Ionization Mass Spectrometry Coupled to Shear Force Microscopy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nguyen, Son N.; Sontag, Ryan L.; Carson, James P.

Constant mode ambient mass spectrometry imaging (MSI) of tissue sections with high lateral resolution of better than 10 µm was performed by combining shear force microscopy with nanospray desorption electrospray ionization (nano-DESI). Shear force microscopy enabled precise control of the distance between the sample and nano-DESI probe during MSI experiments and provided information on sample topography. Proof-of-concept experiments were performed using lung and brain tissue sections representing spongy and dense tissues, respectively. Topography images obtained using shear force microscopy were comparable to the results obtained using contact profilometry over the same region of the tissue section. Variations in tissue heightmore » were found to be dependent on the tissue type and were in the range of 0-5 µm for lung tissue and 0-3 µm for brain tissue sections. Ion images of phospholipids obtained in this study are in good agreement with literature data. Normalization of nano-DESI MSI images to the signal of the internal standard added to the extraction solvent allowed us to construct high-resolution ion images free of matrix effects.« less

Functional imaging with low-resolution brain electromagnetic tomography (LORETA): a review.

PubMed

Pascual-Marqui, R D; Esslen, M; Kochi, K; Lehmann, D

2002-01-01

This paper reviews several recent publications that have successfully used the functional brain imaging method known as LORETA. Emphasis is placed on the electrophysiological and neuroanatomical basis of the method, on the localization properties of the method, and on the validation of the method in real experimental human data. Papers that criticize LORETA are briefly discussed. LORETA publications in the 1994-1997 period based localization inference on images of raw electric neuronal activity. In 1998, a series of papers appeared that based localization inference on the statistical parametric mapping methodology applied to high-time resolution LORETA images. Starting in 1999, quantitative neuroanatomy was added to the methodology, based on the digitized Talairach atlas provided by the Brain Imaging Centre, Montreal Neurological Institute. The combination of these methodological developments has placed LORETA at a level that compares favorably to the more classical functional imaging methods, such as PET and fMRI.

The braingraph.org database of high resolution structural connectomes and the brain graph tools.

PubMed

Kerepesi, Csaba; Szalkai, Balázs; Varga, Bálint; Grolmusz, Vince

2017-10-01

Based on the data of the NIH-funded Human Connectome Project, we have computed structural connectomes of 426 human subjects in five different resolutions of 83, 129, 234, 463 and 1015 nodes and several edge weights. The graphs are given in anatomically annotated GraphML format that facilitates better further processing and visualization. For 96 subjects, the anatomically classified sub-graphs can also be accessed, formed from the vertices corresponding to distinct lobes or even smaller regions of interests of the brain. For example, one can easily download and study the connectomes, restricted to the frontal lobes or just to the left precuneus of 96 subjects using the data. Partially directed connectomes of 423 subjects are also available for download. We also present a GitHub-deposited set of tools, called the Brain Graph Tools, for several processing tasks of the connectomes on the site http://braingraph.org.

Flexible, foldable, actively multiplexed, high-density electrode array for mapping brain activity in vivo.

PubMed

Viventi, Jonathan; Kim, Dae-Hyeong; Vigeland, Leif; Frechette, Eric S; Blanco, Justin A; Kim, Yun-Soung; Avrin, Andrew E; Tiruvadi, Vineet R; Hwang, Suk-Won; Vanleer, Ann C; Wulsin, Drausin F; Davis, Kathryn; Gelber, Casey E; Palmer, Larry; Van der Spiegel, Jan; Wu, Jian; Xiao, Jianliang; Huang, Yonggang; Contreras, Diego; Rogers, John A; Litt, Brian

2011-11-13

Arrays of electrodes for recording and stimulating the brain are used throughout clinical medicine and basic neuroscience research, yet are unable to sample large areas of the brain while maintaining high spatial resolution because of the need to individually wire each passive sensor at the electrode-tissue interface. To overcome this constraint, we developed new devices that integrate ultrathin and flexible silicon nanomembrane transistors into the electrode array, enabling new dense arrays of thousands of amplified and multiplexed sensors that are connected using fewer wires. We used this system to record spatial properties of cat brain activity in vivo, including sleep spindles, single-trial visual evoked responses and electrographic seizures. We found that seizures may manifest as recurrent spiral waves that propagate in the neocortex. The developments reported here herald a new generation of diagnostic and therapeutic brain-machine interface devices.

Transcriptional Landscape of the Prenatal Human Brain

PubMed Central

Miller, Jeremy A.; Ding, Song-Lin; Sunkin, Susan M.; Smith, Kimberly A; Ng, Lydia; Szafer, Aaron; Ebbert, Amanda; Riley, Zackery L.; Aiona, Kaylynn; Arnold, James M.; Bennet, Crissa; Bertagnolli, Darren; Brouner, Krissy; Butler, Stephanie; Caldejon, Shiella; Carey, Anita; Cuhaciyan, Christine; Dalley, Rachel A.; Dee, Nick; Dolbeare, Tim A.; Facer, Benjamin A. C.; Feng, David; Fliss, Tim P.; Gee, Garrett; Goldy, Jeff; Gourley, Lindsey; Gregor, Benjamin W.; Gu, Guangyu; Howard, Robert E.; Jochim, Jayson M.; Kuan, Chihchau L.; Lau, Christopher; Lee, Chang-Kyu; Lee, Felix; Lemon, Tracy A.; Lesnar, Phil; McMurray, Bergen; Mastan, Naveed; Mosqueda, Nerick F.; Naluai-Cecchini, Theresa; Ngo, Nhan-Kiet; Nyhus, Julie; Oldre, Aaron; Olson, Eric; Parente, Jody; Parker, Patrick D.; Parry, Sheana E.; Player, Allison Stevens; Pletikos, Mihovil; Reding, Melissa; Royall, Joshua J.; Roll, Kate; Sandman, David; Sarreal, Melaine; Shapouri, Sheila; Shapovalova, Nadiya V.; Shen, Elaine H.; Sjoquist, Nathan; Slaughterbeck, Clifford R.; Smith, Michael; Sodt, Andy J.; Williams, Derric; Zöllei, Lilla; Fischl, Bruce; Gerstein, Mark B.; Geschwind, Daniel H.; Glass, Ian A.; Hawrylycz, Michael J.; Hevner, Robert F.; Huang, Hao; Jones, Allan R.; Knowles, James A.; Levitt, Pat; Phillips, John W.; Sestan, Nenad; Wohnoutka, Paul; Dang, Chinh; Bernard, Amy; Hohmann, John G.; Lein, Ed S.

2014-01-01

Summary The anatomical and functional architecture of the human brain is largely determined by prenatal transcriptional processes. We describe an anatomically comprehensive atlas of mid-gestational human brain, including de novo reference atlases, in situ hybridization, ultra-high resolution magnetic resonance imaging (MRI) and microarray analysis on highly discrete laser microdissected brain regions. In developing cerebral cortex, transcriptional differences are found between different proliferative and postmitotic layers, wherein laminar signatures reflect cellular composition and developmental processes. Cytoarchitectural differences between human and mouse have molecular correlates, including species differences in gene expression in subplate, although surprisingly we find minimal differences between the inner and human-expanded outer subventricular zones. Both germinal and postmitotic cortical layers exhibit fronto-temporal gradients, with particular enrichment in frontal lobe. Finally, many neurodevelopmental disorder and human evolution-related genes show patterned expression, potentially underlying unique features of human cortical formation. These data provide a rich, freely-accessible resource for understanding human brain development. PMID:24695229

Improving whole brain structural MRI at 4.7 Tesla using 4 irregularly shaped receiver coils.

PubMed

Carmichael, David W; Thomas, David L; De Vita, Enrico; Fernández-Seara, Maria A; Chhina, Navjeet; Cooper, Mark; Sunderland, Colin; Randell, Chris; Turner, Robert; Ordidge, Roger J

2006-09-01

Both higher magnetic field strengths (> or =3 T) and multiple receiver "array coils" can provide increased signal-to-noise ratio (SNR) for MRI. This increase in SNR can be used to obtain images with higher resolution, enabling better visualisation of structures within the human brain. However, high field strength systems also suffer from increased B(1) non-uniformity and increased power deposition, reaching specific absorption rate (SAR) limits more quickly. For these problems to be mitigated, a careful choice of both the pulse sequence design and transmit RF coil is required. This paper describes the use of a prototype array coil consisting of 4 irregularly shaped coils within a standard configuration for neuroimaging at 4.7 T (a head transmit/receive volume coil to minimise SAR and a head gradient insert for maximum gradient performance). With a fast spin echo (FSE) pulse sequence optimised for 4.7 T, this provides dramatically increased quality and resolution over a large brain volume. Using the array coil, a SNR improvement relative to the volume coil of 1-1.5 times in central brain areas and 2-3 times in cortical regions was obtained. Array coil images with a resolution of 352 x 352 x 2000 mum had a SNR of 16.0 to 26.2 in central regions and 19.9 to 34.8 in cortical areas. Such images easily demonstrate cortical myeloarchitecture, while still covering most of the brain in a approximately 12 min scan.

Encoding of Natural Sounds at Multiple Spectral and Temporal Resolutions in the Human Auditory Cortex

PubMed Central

Santoro, Roberta; Moerel, Michelle; De Martino, Federico; Goebel, Rainer; Ugurbil, Kamil; Yacoub, Essa; Formisano, Elia

2014-01-01

Functional neuroimaging research provides detailed observations of the response patterns that natural sounds (e.g. human voices and speech, animal cries, environmental sounds) evoke in the human brain. The computational and representational mechanisms underlying these observations, however, remain largely unknown. Here we combine high spatial resolution (3 and 7 Tesla) functional magnetic resonance imaging (fMRI) with computational modeling to reveal how natural sounds are represented in the human brain. We compare competing models of sound representations and select the model that most accurately predicts fMRI response patterns to natural sounds. Our results show that the cortical encoding of natural sounds entails the formation of multiple representations of sound spectrograms with different degrees of spectral and temporal resolution. The cortex derives these multi-resolution representations through frequency-specific neural processing channels and through the combined analysis of the spectral and temporal modulations in the spectrogram. Furthermore, our findings suggest that a spectral-temporal resolution trade-off may govern the modulation tuning of neuronal populations throughout the auditory cortex. Specifically, our fMRI results suggest that neuronal populations in posterior/dorsal auditory regions preferably encode coarse spectral information with high temporal precision. Vice-versa, neuronal populations in anterior/ventral auditory regions preferably encode fine-grained spectral information with low temporal precision. We propose that such a multi-resolution analysis may be crucially relevant for flexible and behaviorally-relevant sound processing and may constitute one of the computational underpinnings of functional specialization in auditory cortex. PMID:24391486

Enhanced Sensitivity for High Spatial Resolution Lipid Analysis by Negative Ion Mode MALDI Imaging Mass Spectrometry

PubMed Central

Angel, Peggi M.; Spraggins, Jeffrey M.; Baldwin, H. Scott; Caprioli, Richard

2012-01-01

We have achieved enhanced lipid imaging to a ~10 μm spatial resolution using negative ion mode matrix assisted laser desorption ionization (MALDI) imaging mass spectrometry, sublimation of 2,5-dihydroxybenzoic acid as the MALDI matrix and a sample preparation protocol that uses aqueous washes. We report on the effect of treating tissue sections by washing with volatile buffers at different pHs prior to negative ion mode lipid imaging. The results show that washing with ammonium formate, pH 6.4, or ammonium acetate, pH 6.7, significantly increases signal intensity and number of analytes recorded from adult mouse brain tissue sections. Major lipid species measured were glycerophosphoinositols, glycerophosphates, glycerolphosphoglycerols, glycerophosphoethanolamines, glycerophospho-serines, sulfatides, and gangliosides. Ion images from adult mouse brain sections that compare washed and unwashed sections are presented and show up to fivefold increases in ion intensity for washed tissue. The sample preparation protocol has been found to be applicable across numerous organ types and significantly expands the number of lipid species detectable by imaging mass spectrometry at high spatial resolution. PMID:22243218

Development of large field-of-view two photon microscopy for imaging mouse cortex (Conference Presentation)

NASA Astrophysics Data System (ADS)

Bumstead, Jonathan; Côté, Daniel C.; Culver, Joseph P.

2017-02-01

Spontaneous neuronal activity has been measured at cellular resolution in mice, zebrafish, and C. elegans using optical sectioning microscopy techniques, such as light sheet microscopy (LSM) and two photon microscopy (TPM). Recent improvements in these modalities and genetically encoded calcium indicators (GECI's) have enabled whole brain imaging of calcium dynamics in zebrafish and C. elegans. However, these whole brain microscopy studies have not been extended to mice due to the limited field of view (FOV) of TPM and the cumbersome geometry of LSM. Conventional TPM is restricted to diffraction limited imaging over this small FOV (around 500 x 500 microns) due to the use of high magnification objectives (e.g. 1.0 NA; 20X) and the aberrations introduced by relay optics used in scanning the beam across the sample. To overcome these limitations, we have redesigned the entire optical path of the two photon microscope (scanning optics and objective lens) to support a field of view of Ø7 mm with relatively high spatial resolution (<10 microns). Using optical engineering software Zemax, we designed our system with commercially available optics that minimize astigmatism, field curvature, chromatic focal shift, and vignetting. Performance of the system was also tested experimentally with fluorescent beads in agarose, fixed samples, and in vivo structural imaging. Our large-FOV TPM provides a modality capable of studying distributed brain networks in mice at cellular resolution.

A three-wavelength multi-channel brain functional imager based on digital lock-in photon-counting technique

NASA Astrophysics Data System (ADS)

Ding, Xuemei; Wang, Bingyuan; Liu, Dongyuan; Zhang, Yao; He, Jie; Zhao, Huijuan; Gao, Feng

2018-02-01

During the past two decades there has been a dramatic rise in the use of functional near-infrared spectroscopy (fNIRS) as a neuroimaging technique in cognitive neuroscience research. Diffuse optical tomography (DOT) and optical topography (OT) can be employed as the optical imaging techniques for brain activity investigation. However, most current imagers with analogue detection are limited by sensitivity and dynamic range. Although photon-counting detection can significantly improve detection sensitivity, the intrinsic nature of sequential excitations reduces temporal resolution. To improve temporal resolution, sensitivity and dynamic range, we develop a multi-channel continuous-wave (CW) system for brain functional imaging based on a novel lock-in photon-counting technique. The system consists of 60 Light-emitting device (LED) sources at three wavelengths of 660nm, 780nm and 830nm, which are modulated by current-stabilized square-wave signals at different frequencies, and 12 photomultiplier tubes (PMT) based on lock-in photon-counting technique. This design combines the ultra-high sensitivity of the photon-counting technique with the parallelism of the digital lock-in technique. We can therefore acquire the diffused light intensity for all the source-detector pairs (SD-pairs) in parallel. The performance assessments of the system are conducted using phantom experiments, and demonstrate its excellent measurement linearity, negligible inter-channel crosstalk, strong noise robustness and high temporal resolution.

Intraoperative Functional Ultrasound Imaging of Human Brain Activity.

PubMed

Imbault, Marion; Chauvet, Dorian; Gennisson, Jean-Luc; Capelle, Laurent; Tanter, Mickael

2017-08-04

The functional mapping of brain activity is essential to perform optimal glioma surgery and to minimize the risk of postoperative deficits. We introduce a new, portable neuroimaging modality of the human brain based on functional ultrasound (fUS) for deep functional cortical mapping. Using plane-wave transmissions at an ultrafast frame rate (1 kHz), fUS is performed during surgery to measure transient changes in cerebral blood volume with a high spatiotemporal resolution (250 µm, 1 ms). fUS identifies, maps and differentiates regions of brain activation during task-evoked cortical responses within the depth of a sulcus in both awake and anaesthetized patients.

Neurosarcoidosis associated with hypersomnolence treated with corticosteroids and brain irradiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rubinstein, I.; Gray, T.A.; Moldofsky, H.

1988-07-01

Narcoleptic features developed in a young man with CNS sarcoidosis. This was associated with a structural lesion in the hypothalamus as demonstrated on CT scans of the head. The diagnosis of narcolepsy was established by compatible clinical history and the Multiple Sleep Latency Test. Treatment with high-dose corticosteroids was ineffective, but when the low-dose, whole-brain irradiation was added, complete resolution of the narcoleptic features ensued.

Ultramicroscopy as a novel tool to unravel the tropism of AAV gene therapy vectors in the brain.

PubMed

Alves, Sandro; Bode, Julia; Bemelmans, Alexis-Pierre; von Kalle, Christof; Cartier, Nathalie; Tews, Björn

2016-06-20

Recombinant adeno-associated viral (AAV) vectors have advanced to the vanguard of gene therapy. Numerous naturally occurring serotypes have been used to target cells in various tissues. There is a strong need for fast and dynamic methods which efficiently unravel viral tropism in whole organs. Ultramicroscopy (UM) is a novel fluorescence microscopy technique that images optically cleared undissected specimens, achieving good resolutions at high penetration depths while being non-destructive. UM was applied to obtain high-resolution 3D analysis of AAV transduction in adult mouse brains, especially in the hippocampus, a region of interest for Alzheimer's disease therapy. We separately or simultaneously compared transduction efficacies for commonly used serotypes (AAV9 and AAVrh10) using fluorescent reporter expression. We provide a detailed comparative and quantitative analysis of the transduction profiles. UM allowed a rapid analysis of marker fluorescence expression in neurons with intact projections deep inside the brain, in defined anatomical structures. Major hippocampal neuronal transduction was observed with both vectors, with slightly better efficacy for AAV9 in UM. Glial response and synaptic marker expression did not change post transduction.We propose UM as a novel valuable complementary tool to efficiently and simultaneously unravel tropism of different viruses in a single non-dissected adult rodent brain.

Noninvasive photoacoustic computed tomography of mouse brain metabolism in vivo

NASA Astrophysics Data System (ADS)

Yao, Junjie; Xia, Jun; Maslov, Konstantin; Avanaki, Mohammadreza R. N.; Tsytsarev, Vassiliy; Demchenko, Alexei V.; Wang, Lihong V.

2013-03-01

To control the overall action of the body, brain consumes a large amount of energy in proportion to its volume. In humans and many other species, the brain gets most of its energy from oxygen-dependent metabolism of glucose. An abnormal metabolic rate of glucose and/or oxygen usually reflects a diseased status of brain, such as cancer or Alzheimer's disease. We have demonstrated the feasibility of imaging mouse brain metabolism using photoacoustic computed tomography (PACT), a fast, noninvasive and functional imaging modality with optical contrast and acoustic resolution. Brain responses to forepaw stimulations were imaged transdermally and transcranially. 2-NBDG, which diffuses well across the blood-brain-barrier, provided exogenous contrast for photoacoustic imaging of glucose response. Concurrently, hemoglobin provided endogenous contrast for photoacoustic imaging of hemodynamic response. Glucose and hemodynamic responses were quantitatively unmixed by using two-wavelength measurements. We found that glucose uptake and blood perfusion around the somatosensory region of the contralateral hemisphere were both increased by stimulations, indicating elevated neuron activity. The glucose response amplitude was about half that of the hemodynamic response. While the glucose response area was more homogenous and confined within the somatosensory region, the hemodynamic response area showed a clear vascular pattern and spread about twice as wide as that of the glucose response. The PACT of mouse brain metabolism was validated by high-resolution open-scalp OR-PAM and fluorescence imaging. Our results demonstrate that 2-NBDG-enhanced PACT is a promising tool for noninvasive studies of brain metabolism.

A fast atlas-guided high density diffuse optical tomography system for brain imaging

NASA Astrophysics Data System (ADS)

Dai, Xianjin; Zhang, Tao; Yang, Hao; Jiang, Huabei

2017-02-01

Near infrared spectroscopy (NIRS) is an emerging functional brain imaging tool capable of assessing cerebral concentrations of oxygenated hemoglobin (HbO) and deoxygenated hemoglobin (HbR) during brain activation noninvasively. As an extension of NIRS, diffuse optical tomography (DOT) not only shares the merits of providing continuous readings of cerebral oxygenation, but also has the ability to provide spatial resolution in the millimeter scale. Based on the scattering and absorption properties of nonionizing near-infrared light in biological tissue, DOT has been successfully applied in the imaging of breast tumors, osteoarthritis and cortex activations. Here, we present a state-of-art fast high density DOT system suitable for brain imaging. It can achieve up to a 21 Hz sampling rate for a full set of two-wavelength data for 3-D DOT brain image reconstruction. The system was validated using tissue-mimicking brain-model phantom. Then, experiments on healthy subjects were conducted to demonstrate the capability of the system.

Quantification of dopamine transporters in the mouse brain using ultra-high resolution single-photon emission tomography.

PubMed

Acton, Paul D; Choi, Seok-Rye; Plössl, Karl; Kung, Hank F

2002-05-01

Functional imaging of small animals, such as mice and rats, using ultra-high resolution positron emission tomography (PET) and single-photon emission tomography (SPET), is becoming a valuable tool for studying animal models of human disease. While several studies have shown the utility of PET imaging in small animals, few have used SPET in real research applications. In this study we aimed to demonstrate the feasibility of using ultra-high resolution SPET in quantitative studies of dopamine transporters (DAT) in the mouse brain. Four healthy ICR male mice were injected with (mean+/-SD) 704+/-154 MBq [(99m)Tc]TRODAT-1, and scanned using an ultra-high resolution SPET system equipped with pinhole collimators (spatial resolution 0.83 mm at 3 cm radius of rotation). Each mouse had two studies, to provide an indication of test-retest reliability. Reference tissue kinetic modeling analysis of the time-activity data in the striatum and cerebellum was used to quantitate the availability of DAT. A simple equilibrium ratio of striatum to cerebellum provided another measure of DAT binding. The SPET imaging results were compared against ex vivo biodistribution data from the striatum and cerebellum. The mean distribution volume ratio (DVR) from the reference tissue kinetic model was 2.17+/-0.34, with a test-retest reliability of 2.63%+/-1.67%. The ratio technique gave similar results (DVR=2.03+/-0.38, test-retest reliability=6.64%+/-3.86%), and the ex vivo analysis gave DVR=2.32+/-0.20. Correlations between the kinetic model and the ratio technique ( R(2)=0.86, P<0.001) and the ex vivo data ( R(2)=0.92, P=0.04) were both excellent. This study demonstrated clearly that ultra-high resolution SPET of small animals is capable of accurate, repeatable, and quantitative measures of DAT binding, and should open up the possibility of further studies of cerebral binding sites in mice using pinhole SPET.

Genetics Home Reference: distal 18q deletion syndrome

MedlinePlus

... Veltman JA, van Ravenswaaij-Arts CM. Genotype-phenotype mapping of chromosome 18q deletions by high-resolution array ... L, Pihko H. 18q deletions: clinical, molecular, and brain MRI findings of 14 individuals. Am J Med ...

Flexible Organic Electronics for Use in Neural Sensing

PubMed Central

Bink, Hank; Lai, Yuming; Saudari, Sangameshwar R.; Helfer, Brian; Viventi, Jonathan; Van der Spiegel, Jan; Litt, Brian; Kagan, Cherie

2016-01-01

Recent research in brain-machine interfaces and devices to treat neurological disease indicate that important network activity exists at temporal and spatial scales beyond the resolution of existing implantable devices. High density, active electrode arrays hold great promise in enabling high-resolution interface with the brain to access and influence this network activity. Integrating flexible electronic devices directly at the neural interface can enable thousands of multiplexed electrodes to be connected using many fewer wires. Active electrode arrays have been demonstrated using flexible, inorganic silicon transistors. However, these approaches may be limited in their ability to be cost-effectively scaled to large array sizes (8×8 cm). Here we show amplifiers built using flexible organic transistors with sufficient performance for neural signal recording. We also demonstrate a pathway for a fully integrated, amplified and multiplexed electrode array built from these devices. PMID:22255558

Approximating high angular resolution apparent diffusion coefficient profiles using spherical harmonics under BiGaussian assumption

NASA Astrophysics Data System (ADS)

Cao, Ning; Liang, Xuwei; Zhuang, Qi; Zhang, Jun

2009-02-01

Magnetic Resonance Imaging (MRI) techniques have achieved much importance in providing visual and quantitative information of human body. Diffusion MRI is the only non-invasive tool to obtain information of the neural fiber networks of the human brain. The traditional Diffusion Tensor Imaging (DTI) is only capable of characterizing Gaussian diffusion. High Angular Resolution Diffusion Imaging (HARDI) extends its ability to model more complex diffusion processes. Spherical harmonic series truncated to a certain degree is used in recent studies to describe the measured non-Gaussian Apparent Diffusion Coefficient (ADC) profile. In this study, we use the sampling theorem on band-limited spherical harmonics to choose a suitable degree to truncate the spherical harmonic series in the sense of Signal-to-Noise Ratio (SNR), and use Monte Carlo integration to compute the spherical harmonic transform of human brain data obtained from icosahedral schema.

Computation of a high-resolution MRI 3D stereotaxic atlas of the sheep brain.

PubMed

Ella, Arsène; Delgadillo, José A; Chemineau, Philippe; Keller, Matthieu

2017-02-15

The sheep model was first used in the fields of animal reproduction and veterinary sciences and then was utilized in fundamental and preclinical studies. For more than a decade, magnetic resonance (MR) studies performed on this model have been increasingly reported, especially in the field of neuroscience. To contribute to MR translational neuroscience research, a brain template and an atlas are necessary. We have recently generated the first complete T1-weighted (T1W) and T2W MR population average images (or templates) of in vivo sheep brains. In this study, we 1) defined a 3D stereotaxic coordinate system for previously established in vivo population average templates; 2) used deformation fields obtained during optimized nonlinear registrations to compute nonlinear tissues or prior probability maps (nlTPMs) of cerebrospinal fluid (CSF), gray matter (GM), and white matter (WM) tissues; 3) delineated 25 external and 28 internal sheep brain structures by segmenting both templates and nlTPMs; and 4) annotated and labeled these structures using an existing histological atlas. We built a quality high-resolution 3D atlas of average in vivo sheep brains linked to a reference stereotaxic space. The atlas and nlTPMs, associated with previously computed T1W and T2W in vivo sheep brain templates and nlTPMs, provide a complete set of imaging space that are able to be imported into other imaging software programs and could be used as standardized tools for neuroimaging studies or other neuroscience methods, such as image registration, image segmentation, identification of brain structures, implementation of recording devices, or neuronavigation. J. Comp. Neurol. 525:676-692, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

High spatial resolution technique for SPECT using a fan-beam collimator

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ichihar, T.; Nambu, K.; Motomura, N.

1993-08-01

The physical characteristics of the collimator cause degradation of resolution with increasing distance from the collimator surface. A new convolutional backprojection algorithm has been derived for fanbeam SPECT data without rebinding into parallel beam geometry. The projections are filtered and then backprojected into the area within an isosceles triangle whose vertex is the focal point of the fan-beam and whose base is the fan-beam collimator face, and outside of the circle whose center is located midway between the focal point and the center of rotation and whose diameter is the distance between the focal point and the center of rotation.more » Consequently the backprojected area is close to the collimator surface. This algorithm has been implemented on a GCA-9300A SPECT system showing good results with both phantom and patient studies. The SPECT transaxial resolution was 4.6mm FWHM (reconstructed image matrix size of 256x256) at the center of SPECT FOV using UHR (ultra-high-resolution) fan beam collimators for brain study. Clinically, Tc-99m HMPAO and Tc-99m ECD brain data were reconstructed using this algorithm. The reconstruction results were compared with MRI images of the same slice position and showed significantly improved over results obtained with standard reconstruction algorithms.« less

Accurate 3D reconstruction by a new PDS-OSEM algorithm for HRRT

NASA Astrophysics Data System (ADS)

Chen, Tai-Been; Horng-Shing Lu, Henry; Kim, Hang-Keun; Son, Young-Don; Cho, Zang-Hee

2014-03-01

State-of-the-art high resolution research tomography (HRRT) provides high resolution PET images with full 3D human brain scanning. But, a short time frame in dynamic study causes many problems related to the low counts in the acquired data. The PDS-OSEM algorithm was proposed to reconstruct the HRRT image with a high signal-to-noise ratio that provides accurate information for dynamic data. The new algorithm was evaluated by simulated image, empirical phantoms, and real human brain data. Meanwhile, the time activity curve was adopted to validate a reconstructed performance of dynamic data between PDS-OSEM and OP-OSEM algorithms. According to simulated and empirical studies, the PDS-OSEM algorithm reconstructs images with higher quality, higher accuracy, less noise, and less average sum of square error than those of OP-OSEM. The presented algorithm is useful to provide quality images under the condition of low count rates in dynamic studies with a short scan time.

A high-resolution 7-Tesla fMRI dataset from complex natural stimulation with an audio movie.

PubMed

Hanke, Michael; Baumgartner, Florian J; Ibe, Pierre; Kaule, Falko R; Pollmann, Stefan; Speck, Oliver; Zinke, Wolf; Stadler, Jörg

2014-01-01

Here we present a high-resolution functional magnetic resonance (fMRI) dataset - 20 participants recorded at high field strength (7 Tesla) during prolonged stimulation with an auditory feature film ("Forrest Gump"). In addition, a comprehensive set of auxiliary data (T1w, T2w, DTI, susceptibility-weighted image, angiography) as well as measurements to assess technical and physiological noise components have been acquired. An initial analysis confirms that these data can be used to study common and idiosyncratic brain response patterns to complex auditory stimulation. Among the potential uses of this dataset are the study of auditory attention and cognition, language and music perception, and social perception. The auxiliary measurements enable a large variety of additional analysis strategies that relate functional response patterns to structural properties of the brain. Alongside the acquired data, we provide source code and detailed information on all employed procedures - from stimulus creation to data analysis. In order to facilitate replicative and derived works, only free and open-source software was utilized.

Brain BLAQ: Post-hoc thick-section histochemistry for localizing optogenetic constructs in neurons and their distal terminals

PubMed Central

Kupferschmidt, David A.; Cody, Patrick A.; Lovinger, David M.; Davis, Margaret I.

2015-01-01

Optogenetic constructs have revolutionized modern neuroscience, but the ability to accurately and efficiently assess their expression in the brain and associate it with prior functional measures remains a challenge. High-resolution imaging of thick, fixed brain sections would make such post-hoc assessment and association possible; however, thick sections often display autofluorescence that limits their compatibility with fluorescence microscopy. We describe and evaluate a method we call “Brain BLAQ” (Block Lipids and Aldehyde Quench) to rapidly reduce autofluorescence in thick brain sections, enabling efficient axon-level imaging of neurons and their processes in conventional tissue preparations using standard epifluorescence microscopy. Following viral-mediated transduction of optogenetic constructs and fluorescent proteins in mouse cortical pyramidal and dopaminergic neurons, we used BLAQ to assess innervation patterns in the striatum, a region in which autofluorescence often obscures the imaging of fine neural processes. After BLAQ treatment of 250–350 μm-thick brain sections, axons and puncta of labeled afferents were visible throughout the striatum using a standard epifluorescence stereomicroscope. BLAQ histochemistry confirmed that motor cortex (M1) projections preferentially innervated the matrix component of lateral striatum, whereas medial prefrontal cortex projections terminated largely in dorsal striosomes and distinct nucleus accumbens subregions. Ventral tegmental area dopaminergic projections terminated in a similarly heterogeneous pattern within nucleus accumbens and ventral striatum. Using a minimal number of easily manipulated and visualized sections, and microscopes available in most neuroscience laboratories, BLAQ enables simple, high-resolution assessment of virally transduced optogenetic construct expression, and post-hoc association of this expression with molecular markers, physiology and behavior. PMID:25698938

Light sheet theta microscopy for rapid high-resolution imaging of large biological samples.

PubMed

Migliori, Bianca; Datta, Malika S; Dupre, Christophe; Apak, Mehmet C; Asano, Shoh; Gao, Ruixuan; Boyden, Edward S; Hermanson, Ola; Yuste, Rafael; Tomer, Raju

2018-05-29

Advances in tissue clearing and molecular labeling methods are enabling unprecedented optical access to large intact biological systems. These developments fuel the need for high-speed microscopy approaches to image large samples quantitatively and at high resolution. While light sheet microscopy (LSM), with its high planar imaging speed and low photo-bleaching, can be effective, scaling up to larger imaging volumes has been hindered by the use of orthogonal light sheet illumination. To address this fundamental limitation, we have developed light sheet theta microscopy (LSTM), which uniformly illuminates samples from the same side as the detection objective, thereby eliminating limits on lateral dimensions without sacrificing the imaging resolution, depth, and speed. We present a detailed characterization of LSTM, and demonstrate its complementary advantages over LSM for rapid high-resolution quantitative imaging of large intact samples with high uniform quality. The reported LSTM approach is a significant step for the rapid high-resolution quantitative mapping of the structure and function of very large biological systems, such as a clarified thick coronal slab of human brain and uniformly expanded tissues, and also for rapid volumetric calcium imaging of highly motile animals, such as Hydra, undergoing non-isomorphic body shape changes.

Fluorescent nanodiamond tracking reveals intraneuronal transport abnormalities induced by brain-disease-related genetic risk factors

NASA Astrophysics Data System (ADS)

Haziza, Simon; Mohan, Nitin; Loe-Mie, Yann; Lepagnol-Bestel, Aude-Marie; Massou, Sophie; Adam, Marie-Pierre; Le, Xuan Loc; Viard, Julia; Plancon, Christine; Daudin, Rachel; Koebel, Pascale; Dorard, Emilie; Rose, Christiane; Hsieh, Feng-Jen; Wu, Chih-Che; Potier, Brigitte; Herault, Yann; Sala, Carlo; Corvin, Aiden; Allinquant, Bernadette; Chang, Huan-Cheng; Treussart, François; Simonneau, Michel

2017-05-01

Brain diseases such as autism and Alzheimer's disease (each inflicting >1% of the world population) involve a large network of genes displaying subtle changes in their expression. Abnormalities in intraneuronal transport have been linked to genetic risk factors found in patients, suggesting the relevance of measuring this key biological process. However, current techniques are not sensitive enough to detect minor abnormalities. Here we report a sensitive method to measure the changes in intraneuronal transport induced by brain-disease-related genetic risk factors using fluorescent nanodiamonds (FNDs). We show that the high brightness, photostability and absence of cytotoxicity allow FNDs to be tracked inside the branches of dissociated neurons with a spatial resolution of 12 nm and a temporal resolution of 50 ms. As proof of principle, we applied the FND tracking assay on two transgenic mouse lines that mimic the slight changes in protein concentration (∼30%) found in the brains of patients. In both cases, we show that the FND assay is sufficiently sensitive to detect these changes.

The role of neuroimaging in the discovery of processing stages. A review.

PubMed

Mulder, G; Wijers, A A; Lange, J J; Buijink, B M; Mulder, L J; Willemsen, A T; Paans, A M

1995-11-01

In this contribution we show how neuroimaging methods can augment behavioural methods to discover processing stages. Event Related Brain Potentials (ERPs), Brain Electrical Source Analysis (BESA) and regional changes in cerebral blood flow (rCBF) do not necessarily require behavioural responses. With the aid of rCBF we are able to discover several cortical and subcortical brain systems (processors) active in selective attention and memory search tasks. BESA describes cortical activity with high temporal resolution in terms of a limited number of neural generators within these brain systems. The combination of behavioural methods and neuroimaging provides a picture of the functional architecture of the brain. The review is organized around three processors: the Visual, Cognitive and Manual Motor Processors.

Influence of Wiring Cost on the Large-Scale Architecture of Human Cortical Connectivity

PubMed Central

Samu, David; Seth, Anil K.; Nowotny, Thomas

2014-01-01

In the past two decades some fundamental properties of cortical connectivity have been discovered: small-world structure, pronounced hierarchical and modular organisation, and strong core and rich-club structures. A common assumption when interpreting results of this kind is that the observed structural properties are present to enable the brain's function. However, the brain is also embedded into the limited space of the skull and its wiring has associated developmental and metabolic costs. These basic physical and economic aspects place separate, often conflicting, constraints on the brain's connectivity, which must be characterized in order to understand the true relationship between brain structure and function. To address this challenge, here we ask which, and to what extent, aspects of the structural organisation of the brain are conserved if we preserve specific spatial and topological properties of the brain but otherwise randomise its connectivity. We perform a comparative analysis of a connectivity map of the cortical connectome both on high- and low-resolutions utilising three different types of surrogate networks: spatially unconstrained (‘random’), connection length preserving (‘spatial’), and connection length optimised (‘reduced’) surrogates. We find that unconstrained randomisation markedly diminishes all investigated architectural properties of cortical connectivity. By contrast, spatial and reduced surrogates largely preserve most properties and, interestingly, often more so in the reduced surrogates. Specifically, our results suggest that the cortical network is less tightly integrated than its spatial constraints would allow, but more strongly segregated than its spatial constraints would necessitate. We additionally find that hierarchical organisation and rich-club structure of the cortical connectivity are largely preserved in spatial and reduced surrogates and hence may be partially attributable to cortical wiring constraints. In contrast, the high modularity and strong s-core of the high-resolution cortical network are significantly stronger than in the surrogates, underlining their potential functional relevance in the brain. PMID:24699277

Physical principles for scalable neural recording

PubMed Central

Zamft, Bradley M.; Maguire, Yael G.; Shapiro, Mikhail G.; Cybulski, Thaddeus R.; Glaser, Joshua I.; Amodei, Dario; Stranges, P. Benjamin; Kalhor, Reza; Dalrymple, David A.; Seo, Dongjin; Alon, Elad; Maharbiz, Michel M.; Carmena, Jose M.; Rabaey, Jan M.; Boyden, Edward S.; Church, George M.; Kording, Konrad P.

2013-01-01

Simultaneously measuring the activities of all neurons in a mammalian brain at millisecond resolution is a challenge beyond the limits of existing techniques in neuroscience. Entirely new approaches may be required, motivating an analysis of the fundamental physical constraints on the problem. We outline the physical principles governing brain activity mapping using optical, electrical, magnetic resonance, and molecular modalities of neural recording. Focusing on the mouse brain, we analyze the scalability of each method, concentrating on the limitations imposed by spatiotemporal resolution, energy dissipation, and volume displacement. Based on this analysis, all existing approaches require orders of magnitude improvement in key parameters. Electrical recording is limited by the low multiplexing capacity of electrodes and their lack of intrinsic spatial resolution, optical methods are constrained by the scattering of visible light in brain tissue, magnetic resonance is hindered by the diffusion and relaxation timescales of water protons, and the implementation of molecular recording is complicated by the stochastic kinetics of enzymes. Understanding the physical limits of brain activity mapping may provide insight into opportunities for novel solutions. For example, unconventional methods for delivering electrodes may enable unprecedented numbers of recording sites, embedded optical devices could allow optical detectors to be placed within a few scattering lengths of the measured neurons, and new classes of molecularly engineered sensors might obviate cumbersome hardware architectures. We also study the physics of powering and communicating with microscale devices embedded in brain tissue and find that, while radio-frequency electromagnetic data transmission suffers from a severe power–bandwidth tradeoff, communication via infrared light or ultrasound may allow high data rates due to the possibility of spatial multiplexing. The use of embedded local recording and wireless data transmission would only be viable, however, given major improvements to the power efficiency of microelectronic devices. PMID:24187539

Detection of a mixed infection in a culture-negative brain abscess by broad-spectrum bacterial 16S rRNA gene PCR.

PubMed

Keller, Peter M; Rampini, Silvana K; Bloemberg, Guido V

2010-06-01

We describe the identification of two bacterial pathogens from a culture-negative brain abscess by the use of broad-spectrum 16S rRNA gene PCR. Simultaneous detection of Fusobacterium nucleatum and Porphyromonas endodontalis was possible due to a 24-bp length difference of their partially amplified 16S rRNA genes, which allowed separation by high-resolution polyacrylamide gel electrophoresis.

Long-term optical imaging of intrinsic signals in anesthetized and awake monkeys

NASA Astrophysics Data System (ADS)

Roe, Anna W.

2007-04-01

Some exciting new efforts to use intrinsic signal optical imaging methods for long-term studies in anesthetized and awake monkeys are reviewed. The development of such methodologies opens the door for studying behavioral states such as attention, motivation, memory, emotion, and other higher-order cognitive functions. Long-term imaging is also ideal for studying changes in the brain that accompany development, plasticity, and learning. Although intrinsic imaging lacks the temporal resolution offered by dyes, it is a high spatial resolution imaging method that does not require application of any external agents to the brain. The bulk of procedures described here have been developed in the monkey but can be applied to the study of surface structures in any in vivo preparation.

Imaging separation of neuronal from vascular effects of cocaine on rat cortical brain in vivo

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yuan, Z.; Du, C.; Yuan, Z.

MRI techniques to study brain function assume coupling between neuronal activity, metabolism and flow. However, recent evidence of physiological uncoupling between neuronal and cerebrovascular events highlights the need for methods to simultaneously measure these three properties. We report a multimodality optical approach that integrates dual-wavelength laser speckle imaging (measures changes in blood flow, blood volume and hemoglobin oxygenation), digital-frequency-ramping optical coherence tomography (images quantitative 3D vascular network) and Rhod2 fluorescence (images intracellular calcium for measure of neuronal activity) at high spatiotemporal resolutions (30 {micro}m, 10 Hz) and over a large field of view (3 x 5 mm{sup 2}). We applymore » it to assess cocaine's effects in rat cortical brain and show an immediate decrease 3.5 {+-} 0.9 min, phase (1) in the oxygen content of hemoglobin and the cerebral blood flow followed by an overshoot 7.1 {+-} 0.2 min, phase (2) lasting over 20 min whereas Ca{sup 2+} increased immediately (peaked at t = 4.1 {+-} 0.4 min) and remained elevated. This enabled us to identify a delay (2.9 {+-} 0.5 min) between peak neuronal and vascular responses in phase 2. The ability of this multimodality optical approach for simultaneous imaging at high spatiotemporal resolutions permits us to distinguish the vascular versus cellular changes of the brain, thus complimenting other neuroimaging modalities for brain functional studies (e. g., PET, fMRI).« less

17O Relaxation Times in the Rat Brain at 16.4T

PubMed Central

Wiesner, Hannes M.; Balla, Dávid Z.; Shajan, G.; Scheffler, Klaus; Uğurbil, Kâmil; Chen, Wei; Uludağ, Kâmil; Pohmann, Rolf

2015-01-01

Purpose Measurement of the cerebral metabolic rate of oxygen (CMRO2) via direct imaging of the 17O signal can be a valuable tool in neuroscientific research. However, knowledge of the longitudinal and transverse relaxation times of different brain tissue types is required, which is difficult to obtain because of the low sensitivity of natural abundance H217O measurements. Methods Using the improved sensitivity at a field strength of 16.4 T, relaxation time measurements in the rat brain were performed in vivo and postmortem with relatively high spatial resolutions, using a chemical shift imaging sequence. Results In vivo relaxation times of rat brain were found to be T1 = 6.84 ± 0.67 ms and T2* = 1.77 ± 0.04 ms. Postmortem H217O relaxometry at enriched concentrations after inhalation of 17O2 showed similar T2* values for gray (1.87 ± 0.04 ms) and white matter, significantly longer than muscle (1.27 ± 0.05 ms) and shorter than CSF (2.30 ± 0.16 ms). Conclusion Relaxation times of brain H217O were measured for the first time in vivo in different types of tissues with high spatial resolution. Since the relaxation times of H217O are expected to be independent of field strength, our results should help in optimizing the acquisition parameters for experiments also at other MRI field strengths. PMID:26098931

High Slew-Rate Head-Only Gradient for Improving Distortion in Echo Planar Imaging: Preliminary Experience

PubMed Central

Tan, Ek T.; Lee, Seung-Kyun; Weavers, Paul T.; Graziani, Dominic; Piel, Joseph E.; Shu, Yunhong; Huston, John; Bernstein, Matt A.; Foo, Thomas K.F.

2016-01-01

Purpose To investigate the effects on echo planar imaging (EPI) distortion of using high gradient slew rates (SR) of up to 700 T/m/s for in-vivo human brain imaging, with a dedicated, head-only gradient coil. Materials and Methods Simulation studies were first performed to determine the expected echo spacing and distortion reduction in EPI. A head gradient of 42-cm inner diameter and with asymmetric transverse coils was then installed in a whole-body, conventional 3T MRI system. Human subject imaging was performed on five subjects to determine the effects of EPI on echo spacing and signal dropout at various gradient slew rates. The feasibility of whole-brain imaging at 1.5 mm-isotropic spatial resolution was demonstrated with gradient-echo and spin-echo diffusion-weighted EPI. Results As compared to a whole-body gradient coil, the EPI echo spacing in the head-only gradient coil was reduced by 48%. Simulation and in vivo results, respectively, showed up to 25-26% and 19% improvement in signal dropout. Whole-brain imaging with EPI at 1.5 mm spatial resolution provided good whole-brain coverage, spatial linearity, and low spatial distortion effects. Conclusion Our results of human brain imaging with EPI using the compact head gradient coil at slew rates higher than in conventional whole-body MR systems demonstrate substantially improved image distortion, and point to a potential for benefits to non-EPI pulse sequences. PMID:26921117

Resolution Improvements in in Vivo1H NMR Spectra with Increased Magnetic Field Strength

NASA Astrophysics Data System (ADS)

Gruetter, Rolf; Weisdorf, Sally A.; Rajanayagan, Vasantham; Terpstra, Melissa; Merkle, Hellmut; Truwit, Charles L.; Garwood, Michael; Nyberg, Scott L.; Ugurbil, Kâmil

1998-11-01

The measurement of cerebral metabolites using highly homologous localization techniques and similar shimming methods was performed in the human brain at 1.5 and 4 T as well as in the dog and rat brain at 9.4 T. In rat brain, improved resolution was achieved by shimming all first- and second-order shim coils using a fully adiabatic FASTMAP sequence. The spectra showed a clear improvement in spectral resolution for all metabolite resonances with increased field strength. Changes in cerebral glutamine content were clearly observed at 4 T compared to 1.5 T in patients with hepatic encephalopathy. At 9.4 T, glutamine H4 at 2.46 ppm was fully resolved from glutamate H4 at 2.37 ppm, as was the potential resonance from γ-amino-butyric acid at 2.30 ppm and N-acetyl-aspartyl-glutamate at 2.05 ppm. Singlet linewidths were found to be as low as 6 Hz (0.015 ppm) at 9.4 T, indicating a substantial decrease in ppm linewidth with field strength. Furthermore, the methylene peak of creatine was partially resolved from phosphocreatine, indicating a close to 1:1 relationship in gray matter. We conclude that increasing the magnetic field strength increases spectral resolution also for1H NMR, which can lead to more than linear sensitivity gains.

HIV-1 phylogenetic analysis shows HIV-1 transits through the meninges to brain and peripheral tissues.

PubMed

Lamers, Susanna L; Gray, Rebecca R; Salemi, Marco; Huysentruyt, Leanne C; McGrath, Michael S

2011-01-01

Brain infection by the human immunodeficiency virus type 1 (HIV-1) has been investigated in many reports with a variety of conclusions concerning the time of entry and degree of viral compartmentalization. To address these diverse findings, we sequenced HIV-1 gp120 clones from a wide range of brain, peripheral and meningeal tissues from five patients who died from several HIV-1 associated disease pathologies. High-resolution phylogenetic analysis confirmed previous studies that showed a significant degree of compartmentalization in brain and peripheral tissue subpopulations. Some intermixing between the HIV-1 subpopulations was evident, especially in patients that died from pathologies other than HIV-associated dementia. Interestingly, the major tissue harboring virus from both the brain and peripheral tissues was the meninges. These results show that (1) HIV-1 is clearly capable of migrating out of the brain, (2) the meninges are the most likely primary transport tissues, and (3) infected brain macrophages comprise an important HIV reservoir during highly active antiretroviral therapy. Copyright © 2010 Elsevier B.V. All rights reserved.

Intraoperative MR-guided DBS implantation for treating PD and ET

NASA Astrophysics Data System (ADS)

Liu, Haiying; Maxwell, Robert E.; Truwit, Charles L.

2001-05-01

Deep brain stimulator (DBS) implantation is a promising treatment alternative for suppressing the motor tremor symptoms in Parkinson disease (PD) patient. The main objective is to develop a minimally invasive approach using high spatial resolution and soft-tissue contrast MR imaging techniques to guide the surgical placement of DBS. In the MR-guided procedure, the high spatial resolution MR images were obtained intra-operatively and used to target stereotactically a specific deep brain location. The neurosurgery for craniotomy was performed in the front of the magnet outside of the 10 Gauss line. Aided with positional registration assembly for the stereotactic head frame, the target location (VIM or GPi or STN) in deep brain areas was identified and measured from the MR images in reference to the markers in the calibration assembly of the head frame before the burrhole prep. In 20 patients, MR- guided DBS implantations have been performed according to the new methodology. MR-guided DBS implantation at high magnetic field strength has been shown to be feasible and desirable. In addition to the improved outcome, this offers a new surgical approach in which intra-operative visualization is possible during intervention, and any complications such as bleeding can be assessed in situ immediately prior to dural closure.

Analysis of the contribution of experimental bias, experimental noise, and inter-subject biological variability on the assessment of developmental trajectories in diffusion MRI studies of the brain.

PubMed

Sadeghi, Neda; Nayak, Amritha; Walker, Lindsay; Okan Irfanoglu, M; Albert, Paul S; Pierpaoli, Carlo

2015-04-01

Metrics derived from the diffusion tensor, such as fractional anisotropy (FA) and mean diffusivity (MD) have been used in many studies of postnatal brain development. A common finding of previous studies is that these tensor-derived measures vary widely even in healthy populations. This variability can be due to inherent inter-individual biological differences as well as experimental noise. Moreover, when comparing different studies, additional variability can be introduced by different acquisition protocols. In this study we examined scans of 61 individuals (aged 4-22 years) from the NIH MRI study of normal brain development. Two scans were collected with different protocols (low and high resolution). Our goal was to separate the contributions of biological variability and experimental noise to the overall measured variance, as well as to assess potential systematic effects related to the use of different protocols. We analyzed FA and MD in seventeen regions of interest. We found that biological variability for both FA and MD varies widely across brain regions; biological variability is highest for FA in the lateral part of the splenium and body of the corpus callosum along with the cingulum and the superior longitudinal fasciculus, and for MD in the optic radiations and the lateral part of the splenium. These regions with high inter-individual biological variability are the most likely candidates for assessing genetic and environmental effects in the developing brain. With respect to protocol-related effects, the lower resolution acquisition resulted in higher MD and lower FA values for the majority of regions compared with the higher resolution protocol. However, the majority of the regions did not show any age-protocol interaction, indicating similar trajectories were obtained irrespective of the protocol used. Published by Elsevier Inc.

Back-Projection Cortical Potential Imaging: Theory and Results.

PubMed

Haor, Dror; Shavit, Reuven; Shapiro, Moshe; Geva, Amir B

2017-07-01

Electroencephalography (EEG) is the single brain monitoring technique that is non-invasive, portable, passive, exhibits high-temporal resolution, and gives a directmeasurement of the scalp electrical potential. Amajor disadvantage of the EEG is its low-spatial resolution, which is the result of the low-conductive skull that "smears" the currents coming from within the brain. Recording brain activity with both high temporal and spatial resolution is crucial for the localization of confined brain activations and the study of brainmechanismfunctionality, whichis then followed by diagnosis of brain-related diseases. In this paper, a new cortical potential imaging (CPI) method is presented. The new method gives an estimation of the electrical activity on the cortex surface and thus removes the "smearing effect" caused by the skull. The scalp potentials are back-projected CPI (BP-CPI) onto the cortex surface by building a well-posed problem to the Laplace equation that is solved by means of the finite elements method on a realistic head model. A unique solution to the CPI problem is obtained by introducing a cortical normal current estimation technique. The technique is based on the same mechanism used in the well-known surface Laplacian calculation, followed by a scalp-cortex back-projection routine. The BP-CPI passed four stages of validation, including validation on spherical and realistic head models, probabilistic analysis (Monte Carlo simulation), and noise sensitivity tests. In addition, the BP-CPI was compared with the minimum norm estimate CPI approach and found superior for multi-source cortical potential distributions with very good estimation results (CC >0.97) on a realistic head model in the regions of interest, for two representative cases. The BP-CPI can be easily incorporated in different monitoring tools and help researchers by maintaining an accurate estimation for the cortical potential of ongoing or event-related potentials in order to have better neurological inferences from the EEG.

High-Resolution Ambient MS Imaging of Negative Ions in Positive Ion Mode: Using Dicationic Reagents with the Single-Probe

NASA Astrophysics Data System (ADS)

Rao, Wei; Pan, Ning; Tian, Xiang; Yang, Zhibo

2016-01-01

We have used the Single-probe, a miniaturized sampling device utilizing in-situ surface microextraction for ambient mass spectrometry (MS) analysis, for the high resolution MS imaging (MSI) of negatively charged species in the positive ionization mode. Two dicationic compounds, 1,5-pentanediyl-bis(1-butylpyrrolidinium) difluoride [C5(bpyr)2F2] and 1,3-propanediyl-bis(tripropylphosphonium) difluoride [C3(triprp)2F2], were added into the sampling solvent to form 1+ charged adducts with the negatively charged species extracted from tissues. We were able to detect 526 and 322 negatively charged species this way using [C5(bpyr)2F2] and [C3(triprp)2F2], respectively, including oleic acid, arachidonic acid, and several species of phosphatidic acid, phosphoethanolamine, phosphatidylserine, phosphatidylglycerol, phosphatidylinositol, and others. In conjunction with the identification of the non-adduct cations, we have tentatively identified a total number of 1200 and 828 metabolites from mouse brain sections using [C5(bpyr)2F2] and [C3(triprp)2F2], respectively, through high mass accuracy measurements (mass error <5 ppm); MS/MS analyses were also performed to verify the identity of selected species. In addition to the high mass accuracy measurement, we were able to generate high spatial resolution (~17 μm) MS images of mouse brain sections. Our study demonstrated that utilization of dicationic compounds in the surface microextraction with the Single-probe device can perform high mass and spatial resolution ambient MSI measurements of broader types of compounds in tissues. Other reagents can be potentially used with the Single-probe device for a variety of reactive MSI studies to enable the analysis of species that are previously intractable.

Conductive nanogel-interfaced neural microelectrode arrays with electrically controlled in-situ delivery of manganese ions enabling high-resolution MEMRI for synchronous neural tracing with deep brain stimulation.

PubMed

Huang, Wei-Chen; Lo, Yu-Chih; Chu, Chao-Yi; Lai, Hsin-Yi; Chen, You-Yin; Chen, San-Yuan

2017-04-01

Chronic brain stimulation has become a promising physical therapy with increased efficacy and efficiency in the treatment of neurodegenerative diseases. The application of deep brain electrical stimulation (DBS) combined with manganese-enhanced magnetic resonance imaging (MEMRI) provides an unbiased representation of the functional anatomy, which shows the communication between areas of the brain responding to the therapy. However, it is challenging for the current system to provide a real-time high-resolution image because the incorporated MnCl 2 solution through microinjection usually results in image blurring or toxicity due to the uncontrollable diffusion of Mn 2+ . In this study, we developed a new type of conductive nanogel-based neural interface composed of amphiphilic chitosan-modified poly(3,4 -ethylenedioxythiophene) (PMSDT) that can exhibit biomimic structural/mechanical properties and ionic/electrical conductivity comparable to that of Au. More importantly, the PMSDT enables metal-ligand bonding with Mn 2+ ions, so that the system can release Mn 2+ ions rather than MnCl 2 solution directly and precisely controlled by electrical stimulation (ES) to achieve real-time high-resolution MEMRI. With the integration of PMSDT nanogel-based coating in polyimide-based microelectrode arrays, the post-implantation DBS enables frequency-dependent MR imaging in vivo, as well as small focal imaging in response to channel site-specific stimulation on the implant. The MR imaging of the implanted brain treated with 5-min electrical stimulation showed a thalamocortical neuronal pathway after 36 h, confirming the effective activation of a downstream neuronal circuit following DBS. By eliminating the susceptibility to artifact and toxicity, this system, in combination with a MR-compatible implant and a bio-compliant neural interface, provides a harmless and synchronic functional anatomy for DBS. The study demonstrates a model of MEMRI-functionalized DBS based on functional neural interface engineering and controllable delivery technology, which can be utilized in more detailed exploration of the functional anatomy in the treatment of neurodegenerative diseases. Copyright © 2017 Elsevier Ltd. All rights reserved.

First Human Brain Imaging by the jPET-D4 Prototype With a Pre-Computed System Matrix

NASA Astrophysics Data System (ADS)

Yamaya, Taiga; Yoshida, Eiji; Obi, Takashi; Ito, Hiroshi; Yoshikawa, Kyosan; Murayama, Hideo

2008-10-01

The jPET-D4 is a novel brain PET scanner which aims to achieve not only high spatial resolution but also high scanner sensitivity by using 4-layer depth-of-interaction (DOI) information. The dimensions of a system matrix for the jPET-D4 are 3.3 billion (lines-of-response) times 5 million (image elements) when a standard field-of-view (FOV) of 25 cm diameter is sampled with a (1.5 mm)3 voxel . The size of the system matrix is estimated as 117 petabytes (PB) with the accuracy of 8 bytes per element. An on-the-fly calculation is usually used to deal with such a huge system matrix. However we cannot avoid extension of the calculation time when we improve the accuracy of system modeling. In this work, we implemented an alternative approach based on pre-calculation of the system matrix. A histogram-based 3D OS-EM algorithm was implemented on a desktop workstation with 32 GB memory installed. The 117 PB system matrix was compressed under the limited amount of computer memory by (1) eliminating zero elements, (2) applying the DOI compression (DOIC) method and (3) applying rotational symmetry and an axial shift property of the crystal arrangement. Spanning, which degrades axial resolution, was not applied. The system modeling and the DOIC method, which had been validated in 2D image reconstruction, were expanded into 3D implementation. In particular, a new system model including the DOIC transformation was introduced to suppress resolution loss caused by the DOIC method. Experimental results showed that the jPET-D4 has almost uniform spatial resolution of better than 3 mm over the FOV. Finally the first human brain images were obtained with the jPET-D4.

High Efficiency Multi-shot Interleaved Spiral-In/Out Acquisition for High Resolution BOLD fMRI

PubMed Central

Jung, Youngkyoo; Samsonov, Alexey A.; Liu, Thomas T.; Buracas, Giedrius T.

2012-01-01

Growing demand for high spatial resolution BOLD functional MRI faces a challenge of the spatial resolution vs. coverage or temporal resolution tradeoff, which can be addressed by methods that afford increased acquisition efficiency. Spiral acquisition trajectories have been shown to be superior to currently prevalent echo-planar imaging in terms of acquisition efficiency, and high spatial resolution can be achieved by employing multiple-shot spiral acquisition. The interleaved spiral in-out trajectory is preferred over spiral-in due to increased BOLD signal CNR and higher acquisition efficiency than that of spiral-out or non-interleaved spiral in/out trajectories (1), but to date applicability of the multi-shot interleaved spiral in-out for high spatial resolution imaging has not been studied. Herein we propose multi-shot interleaved spiral in-out acquisition and investigate its applicability for high spatial resolution BOLD fMRI. Images reconstructed from interleaved spiral-in and -out trajectories possess artifacts caused by differences in T2* decay, off-resonance and k-space errors associated with the two trajectories. We analyze the associated errors and demonstrate that application of conjugate phase reconstruction and spectral filtering can substantially mitigate these image artifacts. After applying these processing steps, the multishot interleaved spiral in-out pulse sequence yields high BOLD CNR images at in-plane resolution below 1x1 mm while preserving acceptable temporal resolution (4 s) and brain coverage (15 slices of 2 mm thickness). Moreover, this method yields sufficient BOLD CNR at 1.5 mm isotropic resolution for detection of activation in hippocampus associated with cognitive tasks (Stern memory task). The multi-shot interleaved spiral in-out acquisition is a promising technique for high spatial resolution BOLD fMRI applications. PMID:23023395

Comprehensive cellular‐resolution atlas of the adult human brain

PubMed Central

Royall, Joshua J.; Sunkin, Susan M.; Ng, Lydia; Facer, Benjamin A.C.; Lesnar, Phil; Guillozet‐Bongaarts, Angie; McMurray, Bergen; Szafer, Aaron; Dolbeare, Tim A.; Stevens, Allison; Tirrell, Lee; Benner, Thomas; Caldejon, Shiella; Dalley, Rachel A.; Dee, Nick; Lau, Christopher; Nyhus, Julie; Reding, Melissa; Riley, Zackery L.; Sandman, David; Shen, Elaine; van der Kouwe, Andre; Varjabedian, Ani; Write, Michelle; Zollei, Lilla; Dang, Chinh; Knowles, James A.; Koch, Christof; Phillips, John W.; Sestan, Nenad; Wohnoutka, Paul; Zielke, H. Ronald; Hohmann, John G.; Jones, Allan R.; Bernard, Amy; Hawrylycz, Michael J.; Hof, Patrick R.; Fischl, Bruce

2016-01-01

ABSTRACT Detailed anatomical understanding of the human brain is essential for unraveling its functional architecture, yet current reference atlases have major limitations such as lack of whole‐brain coverage, relatively low image resolution, and sparse structural annotation. We present the first digital human brain atlas to incorporate neuroimaging, high‐resolution histology, and chemoarchitecture across a complete adult female brain, consisting of magnetic resonance imaging (MRI), diffusion‐weighted imaging (DWI), and 1,356 large‐format cellular resolution (1 µm/pixel) Nissl and immunohistochemistry anatomical plates. The atlas is comprehensively annotated for 862 structures, including 117 white matter tracts and several novel cyto‐ and chemoarchitecturally defined structures, and these annotations were transferred onto the matching MRI dataset. Neocortical delineations were done for sulci, gyri, and modified Brodmann areas to link macroscopic anatomical and microscopic cytoarchitectural parcellations. Correlated neuroimaging and histological structural delineation allowed fine feature identification in MRI data and subsequent structural identification in MRI data from other brains. This interactive online digital atlas is integrated with existing Allen Institute for Brain Science gene expression atlases and is publicly accessible as a resource for the neuroscience community. J. Comp. Neurol. 524:3127–3481, 2016. © 2016 The Authors The Journal of Comparative Neurology Published by Wiley Periodicals, Inc. PMID:27418273

Automated generation of massive image knowledge collections using Microsoft Live Labs Pivot to promote neuroimaging and translational research.

PubMed

Viangteeravat, Teeradache; Anyanwu, Matthew N; Ra Nagisetty, Venkateswara; Kuscu, Emin

2011-07-15

Massive datasets comprising high-resolution images, generated in neuro-imaging studies and in clinical imaging research, are increasingly challenging our ability to analyze, share, and filter such images in clinical and basic translational research. Pivot collection exploratory analysis provides each user the ability to fully interact with the massive amounts of visual data to fully facilitate sufficient sorting, flexibility and speed to fluidly access, explore or analyze the massive image data sets of high-resolution images and their associated meta information, such as neuro-imaging databases from the Allen Brain Atlas. It is used in clustering, filtering, data sharing and classifying of the visual data into various deep zoom levels and meta information categories to detect the underlying hidden pattern within the data set that has been used. We deployed prototype Pivot collections using the Linux CentOS running on the Apache web server. We also tested the prototype Pivot collections on other operating systems like Windows (the most common variants) and UNIX, etc. It is demonstrated that the approach yields very good results when compared with other approaches used by some researchers for generation, creation, and clustering of massive image collections such as the coronal and horizontal sections of the mouse brain from the Allen Brain Atlas. Pivot visual analytics was used to analyze a prototype of dataset Dab2 co-expressed genes from the Allen Brain Atlas. The metadata along with high-resolution images were automatically extracted using the Allen Brain Atlas API. It is then used to identify the hidden information based on the various categories and conditions applied by using options generated from automated collection. A metadata category like chromosome, as well as data for individual cases like sex, age, and plan attributes of a particular gene, is used to filter, sort and to determine if there exist other genes with a similar characteristics to Dab2. And online access to the mouse brain pivot collection can be viewed using the link http://edtech-dev.uthsc.edu/CTSI/teeDev1/unittest/PaPa/collection.html (user name: tviangte and password: demome) Our proposed algorithm has automated the creation of large image Pivot collections; this will enable investigators of clinical research projects to easily and quickly analyse the image collections through a perspective that is useful for making critical decisions about the image patterns discovered.

The study of brain activity during the observation of commercial advertising by using high resolution EEG techniques.

PubMed

Vecchiato, Giovanni; Astolfi, Laura; De Vico Fallani, Fabrizio; Salinari, Serenella; Cincotti, Febo; Aloise, Fabio; Mattia, Donatella; Marciani, Maria Grazia; Bianchi, Luigi; Soranzo, Ramon; Babiloni, Fabio

2009-01-01

In this paper we illustrate the capability of tracking brain activity during the observation of commercial TV spots by using advanced high resolution EEG statistical techniques in time and frequency domains. In particular, we analyzed the statistically significant cortical spectral power activity in different frequency bands during the observation of a commercial video clip related to the use of a beer in a group of 13 normal subjects. In addition, a TV speech of the prime minister of Italy was analyzed in two groups of swing and "supporter" voters. Results suggested that the cortical activity during the observation of commercial spots could vary consistently across the spot. This fact suggest the possibility to remove the part of the spot that are not particularly attractive by using those cerebral indexes. The cortical activity during the observation of the political speech indicated a major cortical activity in the supporters group when compared to the swing voters. In this case, it is possible to conclude that the communication proposed has failed to raise attention or interest on swing voters. In conclusions, high resolution EEG have been proved able to generate useful insights about the particular fruition of TV messages, related to both commercial as well as political fields.

Simultaneous imaging of oxygen tension and blood flow in animals using a digital micromirror device.

PubMed

Ponticorvo, Adrien; Dunn, Andrew K

2010-04-12

In this study we present a novel imaging method that combines high resolution cerebral blood flow imaging with a highly flexible map of absolute pO(2). In vivo measurements of pO(2) in animals using phosphorescence quenching is a well established method, and is preferable over electrical probes which are inherently invasive and are limited to single point measurements. However, spatially resolved pO(2) measurements using phosphorescence lifetime quenching typically require expensive cameras to obtain images of pO(2) and often suffer from poor signal to noise. Our approach enables us to retain the high temporal resolution and sensitivity of single point detection of phosphorescence by using a digital micromirror device (DMD) to selectively illuminate arbitrarily shaped regions of tissue. In addition, by simultaneously using Laser Speckle Contrast Imaging (LSCI) to measure relative blood flow, we can better examine the relationship between blood flow and absolute pO(2). We successfully used this instrument to study changes that occur during ischemic conditions in the brain with enough spatial resolution to clearly distinguish different regions. This novel instrument will provide researchers with an inexpensive and improved technique to examine multiple hemodynamic parameters simultaneously in the brain as well as other tissues.

Unwarping confocal microscopy images of bee brains by nonrigid registration to a magnetic resonance microscopy image.

PubMed

Rohlfing, Torsten; Schaupp, Frank; Haddad, Daniel; Brandt, Robert; Haase, Axel; Menzel, Randolf; Maurer, Calvin R

2005-01-01

Confocal microscopy (CM) is a powerful image acquisition technique that is well established in many biological applications. It provides 3-D acquisition with high spatial resolution and can acquire several different channels of complementary image information. Due to the specimen extraction and preparation process, however, the shapes of imaged objects may differ considerably from their in vivo appearance. Magnetic resonance microscopy (MRM) is an evolving variant of magnetic resonance imaging, which achieves microscopic resolutions using a high magnetic field and strong magnetic gradients. Compared to CM imaging, MRM allows for in situ imaging and is virtually free of geometrical distortions. We propose to combine the advantages of both methods by unwarping CM images using a MRM reference image. Our method incorporates a sequence of image processing operators applied to the MRM image, followed by a two-stage intensity-based registration to compute a nonrigid coordinate transformation between the CM images and the MRM image. We present results obtained using CM images from the brains of 20 honey bees and a MRM image of an in situ bee brain. Copyright 2005 Society of Photo-Optical Instrumentation Engineers.

Non-contact time-domain imaging of functional brain activation and heterogeneity of superficial signals

NASA Astrophysics Data System (ADS)

Wabnitz, H.; Mazurenka, M.; Di Sieno, L.; Contini, D.; Dalla Mora, A.; Farina, A.; Hoshi, Y.; Kirilina, E.; Macdonald, R.; Pifferi, A.

2017-07-01

Non-contact scanning at small source-detector separation enables imaging of cerebral and extracranial signals at high spatial resolution and their separation based on early and late photons accounting for the related spatio-temporal characteristics.

[High resolution reconstruction of PET images using the iterative OSEM algorithm].

PubMed

Doll, J; Henze, M; Bublitz, O; Werling, A; Adam, L E; Haberkorn, U; Semmler, W; Brix, G

2004-06-01

Improvement of the spatial resolution in positron emission tomography (PET) by incorporation of the image-forming characteristics of the scanner into the process of iterative image reconstruction. All measurements were performed at the whole-body PET system ECAT EXACT HR(+) in 3D mode. The acquired 3D sinograms were sorted into 2D sinograms by means of the Fourier rebinning (FORE) algorithm, which allows the usage of 2D algorithms for image reconstruction. The scanner characteristics were described by a spatially variant line-spread function (LSF), which was determined from activated copper-64 line sources. This information was used to model the physical degradation processes in PET measurements during the course of 2D image reconstruction with the iterative OSEM algorithm. To assess the performance of the high-resolution OSEM algorithm, phantom measurements performed at a cylinder phantom, the hotspot Jaszczack phantom, and the 3D Hoffmann brain phantom as well as different patient examinations were analyzed. Scanner characteristics could be described by a Gaussian-shaped LSF with a full-width at half-maximum increasing from 4.8 mm at the center to 5.5 mm at a radial distance of 10.5 cm. Incorporation of the LSF into the iteration formula resulted in a markedly improved resolution of 3.0 and 3.5 mm, respectively. The evaluation of phantom and patient studies showed that the high-resolution OSEM algorithm not only lead to a better contrast resolution in the reconstructed activity distributions but also to an improved accuracy in the quantification of activity concentrations in small structures without leading to an amplification of image noise or even the occurrence of image artifacts. The spatial and contrast resolution of PET scans can markedly be improved by the presented image restauration algorithm, which is of special interest for the examination of both patients with brain disorders and small animals.

Design of a Multi-Pinhole Collimator for I-123 DaTscan Imaging on Dual-Headed SPECT Systems in Combination with a Fan-Beam Collimator.

PubMed

King, Michael A; Mukherjee, Joyeeta M; Könik, Arda; Zubal, I George; Dey, Joyoni; Licho, Robert

2016-02-01

For the 2011 FDA approved Parkinson's Disease (PD) SPECT imaging agent I-123 labeled DaTscan, the volume of interest (VOI) is the interior portion of the brain. However imaging of the occipital lobe is also required with PD for calculation of the striatal binding ratio (SBR), a parameter of significance in early diagnosis, differentiation of PD from other disorders with similar clinical presentations, and monitoring progression. Thus we propose the usage of a combination of a multi-pinhole (MPH) collimator on one head of the SPECT system and a fan-beam on the other. The MPH would be designed to provide high resolution and sensitivity for imaging of the interior portion of the brain. The fan-beam collimator would provide lower resolution but complete sampling of the brain addressing data sufficiency and allowing a volume-of-interest to be defined over the occipital lobe for calculation of SBR's. Herein we focus on the design of the MPH component of the combined system. Combined reconstruction will be addressed in a subsequent publication. An analysis of 46 clinical DaTscan studies was performed to provide information to define the VOI, and design of a MPH collimator to image this VOI. The system spatial resolution for the MPH was set to 4.7 mm, which is comparable to that of clinical PET systems, and significantly smaller than that of fan-beam collimators employed in SPECT. With this set, we compared system sensitivities for three aperture array designs, and selected the 3 × 3 array due to it being the highest of the three. The combined sensitivity of the apertures for it was similar to that of an ultra-high resolution fan-beam (LEUHRF) collimator, but smaller than that of a high-resolution fan-beam collimator (LEHRF). On the basis of these results we propose the further exploration of this design through simulations, and the development of combined MPH and fan-beam reconstruction.

Detection of a Mixed Infection in a Culture-Negative Brain Abscess by Broad-Spectrum Bacterial 16S rRNA Gene PCR ▿ †

PubMed Central

Keller, Peter M.; Rampini, Silvana K.; Bloemberg, Guido V.

2010-01-01

We describe the identification of two bacterial pathogens from a culture-negative brain abscess by the use of broad-spectrum 16S rRNA gene PCR. Simultaneous detection of Fusobacterium nucleatum and Porphyromonas endodontalis was possible due to a 24-bp length difference of their partially amplified 16S rRNA genes, which allowed separation by high-resolution polyacrylamide gel electrophoresis. PMID:20392909

Light-sheet enhanced resolution of light field microscopy for rapid imaging of large volumes

NASA Astrophysics Data System (ADS)

Madrid Wolff, Jorge; Castro, Diego; Arbeláez, Pablo; Forero-Shelton, Manu

2018-02-01

Whole-brain imaging is challenging because it demands microscopes with high temporal and spatial resolution, which are often at odds, especially in the context of large fields of view. We have designed and built a light-sheet microscope with digital micromirror illumination and light-field detection. On the one hand, light sheets provide high resolution optical sectioning on live samples without compromising their viability. On the other hand, light field imaging makes it possible to reconstruct full volumes of relatively large fields of view from a single camera exposure; however, its enhanced temporal resolution comes at the expense of spatial resolution, limiting its applicability. We present an approach to increase the resolution of light field images using DMD-based light sheet illumination. To that end, we develop a method to produce synthetic resolution targets for light field microscopy and a procedure to correct the depth at which planes are refocused with rendering software. We measured the axial resolution as a function of depth and show a three-fold potential improvement with structured illumination, albeit by sacrificing some temporal resolution, also three-fold. This results in an imaging system that may be adjusted to specific needs without having to reassemble and realign it. This approach could be used to image relatively large samples at high rates.

Three-dimensional imaging of the brain cavities in human embryos.

PubMed

Blaas, H G; Eik-Nes, S H; Kiserud, T; Berg, S; Angelsen, B; Olstad, B

1995-04-01

A system for high-resolution three-dimensional imaging of small structures has been developed, based on the Vingmed CFM-800 annular array sector scanner with a 7.5-MHz transducer attached to a PC-based TomTec Echo-Scan unit. A stepper motor rotates the transducer 180 degrees and the complete three-dimensional scan consists of 132 two-dimensional images, video-grabbed and scan-converted into a regular volumetric data set by the TomTec unit. Three normal pregnancies with embryos of gestational age 7, 9 and 10 weeks received a transvaginal examination with special attention to the embryonic/fetal brain. In all three cases, it was possible to obtain high-resolution images of the brain cavities. At 7 weeks, both hemispheres and their connection to the third ventricle were delineated. The isthmus rhombencephali could be visualized. At 9 weeks, the continuous development of the brain cavities could be followed and at 11 weeks the dominating size of the hemispheres could be depicted. It is concluded that present ultrasound technology has reached a stage where structures of only a few millimeters can be imaged in vivo in three-dimensions with a quality that resembles the plaster figures used in embryonic laboratories. The method can become an important tool in future embryological research and also in the detection of early developmental disorders of the embryo.

Inferring common cognitive mechanisms from brain blood-flow lateralization data: a new methodology for fTCD analysis.

PubMed

Meyer, Georg F; Spray, Amy; Fairlie, Jo E; Uomini, Natalie T

2014-01-01

Current neuroimaging techniques with high spatial resolution constrain participant motion so that many natural tasks cannot be carried out. The aim of this paper is to show how a time-locked correlation-analysis of cerebral blood flow velocity (CBFV) lateralization data, obtained with functional TransCranial Doppler (fTCD) ultrasound, can be used to infer cerebral activation patterns across tasks. In a first experiment we demonstrate that the proposed analysis method results in data that are comparable with the standard Lateralization Index (LI) for within-task comparisons of CBFV patterns, recorded during cued word generation (CWG) at two difficulty levels. In the main experiment we demonstrate that the proposed analysis method shows correlated blood-flow patterns for two different cognitive tasks that are known to draw on common brain areas, CWG, and Music Synthesis. We show that CBFV patterns for Music and CWG are correlated only for participants with prior musical training. CBFV patterns for tasks that draw on distinct brain areas, the Tower of London and CWG, are not correlated. The proposed methodology extends conventional fTCD analysis by including temporal information in the analysis of cerebral blood-flow patterns to provide a robust, non-invasive method to infer whether common brain areas are used in different cognitive tasks. It complements conventional high resolution imaging techniques.

Estimating brain age using high-resolution pattern recognition: Younger brains in long-term meditation practitioners.

PubMed

Luders, Eileen; Cherbuin, Nicolas; Gaser, Christian

2016-07-01

Normal aging is known to be accompanied by loss of brain substance. The present study was designed to examine whether the practice of meditation is associated with a reduced brain age. Specific focus was directed at age fifty and beyond, as mid-life is a time when aging processes are known to become more prominent. We applied a recently developed machine learning algorithm trained to identify anatomical correlates of age in the brain translating those into one single score: the BrainAGE index (in years). Using this validated approach based on high-dimensional pattern recognition, we re-analyzed a large sample of 50 long-term meditators and 50 control subjects estimating and comparing their brain ages. We observed that, at age fifty, brains of meditators were estimated to be 7.5years younger than those of controls. In addition, we examined if the brain age estimates change with increasing age. While brain age estimates varied only little in controls, significant changes were detected in meditators: for every additional year over fifty, meditators' brains were estimated to be an additional 1month and 22days younger than their chronological age. Altogether, these findings seem to suggest that meditation is beneficial for brain preservation, effectively protecting against age-related atrophy with a consistently slower rate of brain aging throughout life. Copyright © 2016 Elsevier Inc. All rights reserved.

An Automated Platform for High-Resolution Tissue Imaging Using Nanospray Desorption Electrospray Ionization Mass Spectrometry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lanekoff, Ingela T.; Heath, Brandi S.; Liyu, Andrey V.

2012-10-02

An automated platform has been developed for acquisition and visualization of mass spectrometry imaging (MSI) data using nanospray desorption electrospray ionization (nano-DESI). The new system enables robust operation of the nano-DESI imaging source over many hours. This is achieved by controlling the distance between the sample and the probe by mounting the sample holder onto an automated XYZ stage and defining the tilt of the sample plane. This approach is useful for imaging of relatively flat samples such as thin tissue sections. Custom software called MSI QuickView was developed for visualization of large data sets generated in imaging experiments. MSImore » QuickView enables fast visualization of the imaging data during data acquisition and detailed processing after the entire image is acquired. The performance of the system is demonstrated by imaging rat brain tissue sections. High resolution mass analysis combined with MS/MS experiments enabled identification of lipids and metabolites in the tissue section. In addition, high dynamic range and sensitivity of the technique allowed us to generate ion images of low-abundance isobaric lipids. High-spatial resolution image acquired over a small region of the tissue section revealed the spatial distribution of an abundant brain metabolite, creatine, in the white and gray matter that is consistent with the literature data obtained using magnetic resonance spectroscopy.« less

Using High Spatial Resolution to Improve BOLD fMRI Detection at 3T

PubMed Central

Claise, Béatrice; Jean, Betty

2015-01-01

For different functional magnetic resonance imaging experiments using blood oxygenation level-dependent (BOLD) contrast, the acquisition of T 2*-weighted scans at a high spatial resolution may be advantageous in terms of time-course signal-to-noise ratio and of BOLD sensitivity when the regions are prone to susceptibility artifacts. In this study, we explore this solution by examining how spatial resolution influences activations elicited when appetizing food pictures are viewed. Twenty subjects were imaged at 3 T with two different voxel volumes, 3.4 μl and 27 μl. Despite the diminution of brain coverage, we found that high-resolution acquisition led to a better detection of activations. Though known to suffer to different degrees from susceptibility artifacts, the activations detected by high spatial resolution were notably consistent with those reported in published activation likelihood estimation meta-analyses, corresponding to taste-responsive regions. Furthermore, these regions were found activated bilaterally, in contrast with previous findings. Both the reduction of partial volume effect, which improves BOLD contrast, and the mitigation of susceptibility artifact, which boosts the signal to noise ratio in certain regions, explained the better detection noted with high resolution. The present study provides further evidences that high spatial resolution is a valuable solution for human BOLD fMRI, especially for studying food-related stimuli. PMID:26550990

Neuronal chronometry of target detection: fusion of hemodynamic and event-related potential data.

PubMed

Calhoun, V D; Adali, T; Pearlson, G D; Kiehl, K A

2006-04-01

Event-related potential (ERP) studies of the brain's response to infrequent, target (oddball) stimuli elicit a sequence of physiological events, the most prominent and well studied being a complex, the P300 (or P3) peaking approximately 300 ms post-stimulus for simple stimuli and slightly later for more complex stimuli. Localization of the neural generators of the human oddball response remains challenging due to the lack of a single imaging technique with good spatial and temporal resolution. Here, we use independent component analyses to fuse ERP and fMRI modalities in order to examine the dynamics of the auditory oddball response with high spatiotemporal resolution across the entire brain. Initial activations in auditory and motor planning regions are followed by auditory association cortex and motor execution regions. The P3 response is associated with brainstem, temporal lobe, and medial frontal activity and finally a late temporal lobe "evaluative" response. We show that fusing imaging modalities with different advantages can provide new information about the brain.

High-resolution single photon planar and spect imaging of brain and neck employing a system of two co-registered opposed gamma imaging heads

DOEpatents

Majewski, Stanislaw [Yorktown, VA; Proffitt, James [Newport News, VA

2011-12-06

A compact, mobile, dedicated SPECT brain imager that can be easily moved to the patient to provide in-situ imaging, especially when the patient cannot be moved to the Nuclear Medicine imaging center. As a result of the widespread availability of single photon labeled biomarkers, the SPECT brain imager can be used in many locations, including remote locations away from medical centers. The SPECT imager improves the detection of gamma emission from the patient's head and neck area with a large field of view. Two identical lightweight gamma imaging detector heads are mounted to a rotating gantry and precisely mechanically co-registered to each other at 180 degrees. A unique imaging algorithm combines the co-registered images from the detector heads and provides several SPECT tomographic reconstructions of the imaged object thereby improving the diagnostic quality especially in the case of imaging requiring higher spatial resolution and sensitivity at the same time.

Ultrasonic evaluation of the neonatal brain.

PubMed

Johnson, M L; Rumack, C M

1980-04-01

Ultrasound examination of the infant brain has been performed in selected medical centers for many years. However, the equipment necessary for obtaining satisfactory visualization of the brain has only recently become commercially available. Currently, ultrasonography is an excellent, noninvasive, inexpensive, rapid, and safe imaging modality for the evaluation of hydrocephalus and other pathologic conditions of the neonatal brain. Ventricular size can often be evaluated in infants up to two or three years of age, but a detailed image of the brain parenchyma becomes more difficult to obtain in a term infant after the first two to three months of life. With the use of the water path and high resolution, real-time systems and with the delineation of structures by multiple projections, (axial, coronal, sagittal and occipital), complex abnormalities may be delineated.

Age-Related Effects and Sex Differences in Gray Matter Density, Volume, Mass, and Cortical Thickness from Childhood to Young Adulthood.

PubMed

Gennatas, Efstathios D; Avants, Brian B; Wolf, Daniel H; Satterthwaite, Theodore D; Ruparel, Kosha; Ciric, Rastko; Hakonarson, Hakon; Gur, Raquel E; Gur, Ruben C

2017-05-17

Developmental structural neuroimaging studies in humans have long described decreases in gray matter volume (GMV) and cortical thickness (CT) during adolescence. Gray matter density (GMD), a measure often assumed to be highly related to volume, has not been systematically investigated in development. We used T1 imaging data collected on the Philadelphia Neurodevelopmental Cohort to study age-related effects and sex differences in four regional gray matter measures in 1189 youths ranging in age from 8 to 23 years. Custom T1 segmentation and a novel high-resolution gray matter parcellation were used to extract GMD, GMV, gray matter mass (GMM; defined as GMD × GMV), and CT from 1625 brain regions. Nonlinear models revealed that each modality exhibits unique age-related effects and sex differences. While GMV and CT generally decrease with age, GMD increases and shows the strongest age-related effects, while GMM shows a slight decline overall. Females have lower GMV but higher GMD than males throughout the brain. Our findings suggest that GMD is a prime phenotype for the assessment of brain development and likely cognition and that periadolescent gray matter loss may be less pronounced than previously thought. This work highlights the need for combined quantitative histological MRI studies. SIGNIFICANCE STATEMENT This study demonstrates that different MRI-derived gray matter measures show distinct age and sex effects and should not be considered equivalent but complementary. It is shown for the first time that gray matter density increases from childhood to young adulthood, in contrast with gray matter volume and cortical thickness, and that females, who are known to have lower gray matter volume than males, have higher density throughout the brain. A custom preprocessing pipeline and a novel high-resolution parcellation were created to analyze brain scans of 1189 youths collected as part of the Philadelphia Neurodevelopmental Cohort. A clear understanding of normal structural brain development is essential for the examination of brain-behavior relationships, the study of brain disease, and, ultimately, clinical applications of neuroimaging. Copyright © 2017 the authors 0270-6474/17/375065-09$15.00/0.

Three levels of neuroelectronic interfacing: silicon chips with ion channels, nerve cells, and brain tissue.

PubMed

Fromherz, Peter

2006-12-01

We consider the direct electrical interfacing of semiconductor chips with individual nerve cells and brain tissue. At first, the structure of the cell-chip contact is studied. Then we characterize the electrical coupling of ion channels--the electrical elements of nerve cells--with transistors and capacitors in silicon chips. On that basis it is possible to implement signal transmission between microelectronics and the microionics of nerve cells in both directions. Simple hybrid neuroelectronic systems are assembled with neuron pairs and with small neuronal networks. Finally, the interfacing with capacitors and transistors is extended to brain tissue cultured on silicon chips. The application of highly integrated silicon chips allows an imaging of neuronal activity with high spatiotemporal resolution. The goal of the work is an integration of neuronal network dynamics with digital electronics on a microscopic level with respect to experiments in brain research, medical prosthetics, and information technology.

A high resolution spatiotemporal atlas of gene expression of the developing mouse brain

PubMed Central

Thompson, Carol L.; Ng, Lydia; Menon, Vilas; Martinez, Salvador; Lee, Chang-Kyu; Glattfelder, Katie; Sunkin, Susan M.; Henry, Alex; Lau, Christopher; Dang, Chinh; Garcia-Lopez, Raquel; Martinez-Ferre, Almudena; Pombero, Ana; Rubenstein, John L.R.; Wakeman, Wayne B.; Hohmann, John; Dee, Nick; Sodt, Andrew J.; Young, Rob; Smith, Kimberly; Nguyen, Thuc-Nghi; Kidney, Jolene; Kuan, Leonard; Jeromin, Andreas; Kaykas, Ajamete; Miller, Jeremy; Page, Damon; Orta, Geri; Bernard, Amy; Riley, Zackery; Smith, Simon; Wohnoutka, Paul; Hawrylycz, Mike; Puelles, Luis; Jones, Allan R.

2015-01-01

SUMMARY To provide a temporal framework for the genoarchitecture of brain development, in situ hybridization data were generated for embryonic and postnatal mouse brain at 7 developmental stages for ~2100 genes, processed with an automated informatics pipeline and manually annotated. This resource comprises 434,946 images, 7 reference atlases, an ontogenetic ontology, and tools to explore co-expression of genes across neurodevelopment. Gene sets coinciding with developmental phenomena were identified. A temporal shift in the principles governing the molecular organization of the brain was detected, with transient neuromeric, plate-based organization of the brain present at E11.5 and E13.5. Finally, these data provided a transcription factor code that discriminates brain structures and identifies the developmental age of a tissue, providing a foundation for eventual genetic manipulation or tracking of specific brain structures over development. The resource is available as the Allen Developing Mouse Brain Atlas (developingmouse.brain-map.org). PMID:24952961

Transcriptional landscape of the prenatal human brain.

PubMed

Miller, Jeremy A; Ding, Song-Lin; Sunkin, Susan M; Smith, Kimberly A; Ng, Lydia; Szafer, Aaron; Ebbert, Amanda; Riley, Zackery L; Royall, Joshua J; Aiona, Kaylynn; Arnold, James M; Bennet, Crissa; Bertagnolli, Darren; Brouner, Krissy; Butler, Stephanie; Caldejon, Shiella; Carey, Anita; Cuhaciyan, Christine; Dalley, Rachel A; Dee, Nick; Dolbeare, Tim A; Facer, Benjamin A C; Feng, David; Fliss, Tim P; Gee, Garrett; Goldy, Jeff; Gourley, Lindsey; Gregor, Benjamin W; Gu, Guangyu; Howard, Robert E; Jochim, Jayson M; Kuan, Chihchau L; Lau, Christopher; Lee, Chang-Kyu; Lee, Felix; Lemon, Tracy A; Lesnar, Phil; McMurray, Bergen; Mastan, Naveed; Mosqueda, Nerick; Naluai-Cecchini, Theresa; Ngo, Nhan-Kiet; Nyhus, Julie; Oldre, Aaron; Olson, Eric; Parente, Jody; Parker, Patrick D; Parry, Sheana E; Stevens, Allison; Pletikos, Mihovil; Reding, Melissa; Roll, Kate; Sandman, David; Sarreal, Melaine; Shapouri, Sheila; Shapovalova, Nadiya V; Shen, Elaine H; Sjoquist, Nathan; Slaughterbeck, Clifford R; Smith, Michael; Sodt, Andy J; Williams, Derric; Zöllei, Lilla; Fischl, Bruce; Gerstein, Mark B; Geschwind, Daniel H; Glass, Ian A; Hawrylycz, Michael J; Hevner, Robert F; Huang, Hao; Jones, Allan R; Knowles, James A; Levitt, Pat; Phillips, John W; Sestan, Nenad; Wohnoutka, Paul; Dang, Chinh; Bernard, Amy; Hohmann, John G; Lein, Ed S

2014-04-10

The anatomical and functional architecture of the human brain is mainly determined by prenatal transcriptional processes. We describe an anatomically comprehensive atlas of the mid-gestational human brain, including de novo reference atlases, in situ hybridization, ultra-high-resolution magnetic resonance imaging (MRI) and microarray analysis on highly discrete laser-microdissected brain regions. In developing cerebral cortex, transcriptional differences are found between different proliferative and post-mitotic layers, wherein laminar signatures reflect cellular composition and developmental processes. Cytoarchitectural differences between human and mouse have molecular correlates, including species differences in gene expression in subplate, although surprisingly we find minimal differences between the inner and outer subventricular zones even though the outer zone is expanded in humans. Both germinal and post-mitotic cortical layers exhibit fronto-temporal gradients, with particular enrichment in the frontal lobe. Finally, many neurodevelopmental disorder and human-evolution-related genes show patterned expression, potentially underlying unique features of human cortical formation. These data provide a rich, freely-accessible resource for understanding human brain development.

In vivo imaging and analysis of cerebrovascular hemodynamic responses and tissue oxygenation in the mouse brain.

PubMed

Kisler, Kassandra; Lazic, Divna; Sweeney, Melanie D; Plunkett, Shane; El Khatib, Mirna; Vinogradov, Sergei A; Boas, David A; Sakadži, Sava; Zlokovic, Berislav V

2018-06-01

Cerebrovascular dysfunction has an important role in the pathogenesis of multiple brain disorders. Measurement of hemodynamic responses in vivo can be challenging, particularly as techniques are often not described in sufficient detail and vary between laboratories. We present a set of standardized in vivo protocols that describe high-resolution two-photon microscopy and intrinsic optical signal (IOS) imaging to evaluate capillary and arteriolar responses to a stimulus, regional hemodynamic responses, and oxygen delivery to the brain. The protocol also describes how to measure intrinsic NADH fluorescence to understand how blood O 2 supply meets the metabolic demands of activated brain tissue, and to perform resting-state absolute oxygen partial pressure (pO 2 ) measurements of brain tissue. These methods can detect cerebrovascular changes at far higher resolution than MRI techniques, although the optical nature of these techniques limits their achievable imaging depths. Each individual procedure requires 1-2 h to complete, with two to three procedures typically performed per animal at a time. These protocols are broadly applicable in studies of cerebrovascular function in healthy and diseased brain in any of the existing mouse models of neurological and vascular disorders. All these procedures can be accomplished by a competent graduate student or experienced technician, except the two-photon measurement of absolute pO 2 level, which is better suited to a more experienced, postdoctoral-level researcher.

Cerebral cortex three-dimensional profiling in human fetuses by magnetic resonance imaging

PubMed Central

Sbarbati, Andrea; Pizzini, Francesca; Fabene, Paolo F; Nicolato, Elena; Marzola, Pasquina; Calderan, Laura; Simonati, Alessandro; Longo, Laura; Osculati, Antonio; Beltramello, Alberto

2004-01-01

Seven human fetuses of crown/rump length corresponding to gestational ages ranging from the 12th to the 16th week were studied using a paradigm based on three-dimensional reconstruction of the brain obtained by magnetic resonance imaging (MRI). The aim of the study was to evaluate brain morphology in situ and to describe developmental dynamics during an important period of fetal morphogenesis. Three-dimensional MRI showed the increasing degree of maturation of the brains; fronto-occipital distance, bitemporal distance and occipital angle were examined in all the fetuses. The data were interpreted by correlation with the internal structure as visualized using high-spatial-resolution MRI, acquired using a 4.7-T field intensity magnet with a gradient power of 20 G cm−1. The spatial resolution was sufficient for a detailed detection of five layers, and the contrast was optimized using sequences with different degrees of T1 and T2 weighting. Using the latter, it was possible to visualize the subplate and marginal zones. The cortical thickness was mapped on to the hemispheric surface, describing the thickness gradient from the insular cortex to the periphery of the hemispheres. The study demonstrates the utility of MRI for studying brain development. The method provides a quantitative profiling of the brain, which allows the calculation of important morphological parameters, and it provides informative regarding transient features of the developing brain. PMID:15198688

[Neurological and technical aspects of deep brain stimulation].

PubMed

Voges, J; Krauss, J K

2010-06-01

Deep brain stimulation (DBS) is an important component of the therapy of movement disorders and has almost completely replaced high-frequency coagulation of brain tissue in stereotactic neurosurgery. Despite the functional efficacy of DBS, which in parts is documented on the highest evidence level, the underlying mechanisms are still not completely understood. According to the current state of knowledge electrophysiological and functional data give evidence that high-frequency DBS has an inhibitory effect around the stimulation electrode whilst at the same time axons entering or leaving the stimulated brain area are excited leading to modulation of neuronal networks. The latter effect modifies pathological discharges of neurons in key structures of the basal ganglia network (e.g. irregular bursting activity, oscillations or synchronization) which are found in particular movement disorders such as Parkinson' s disease or dystonia. The introduction of technical standards, such as the integration of high resolution MRI into computer-assisted treatment planning, in combination with special treatment planning software have contributed significantly to the reduction of severe surgical complications (frequency of intracranial hemorrhaging 1-3%) in recent years. Future developments will address the modification of hardware components of the stimulation system, the evaluation of new brain target areas, the simultaneous stimulation of different brain areas and the assessment of different stimulation paradigms (high-frequency vs low-frequency DBS).

On the use of EEG or MEG brain imaging tools in neuromarketing research.

PubMed

Vecchiato, Giovanni; Astolfi, Laura; De Vico Fallani, Fabrizio; Toppi, Jlenia; Aloise, Fabio; Bez, Francesco; Wei, Daming; Kong, Wanzeng; Dai, Jounging; Cincotti, Febo; Mattia, Donatella; Babiloni, Fabio

2011-01-01

Here we present an overview of some published papers of interest for the marketing research employing electroencephalogram (EEG) and magnetoencephalogram (MEG) methods. The interest for these methodologies relies in their high-temporal resolution as opposed to the investigation of such problem with the functional Magnetic Resonance Imaging (fMRI) methodology, also largely used in the marketing research. In addition, EEG and MEG technologies have greatly improved their spatial resolution in the last decades with the introduction of advanced signal processing methodologies. By presenting data gathered through MEG and high resolution EEG we will show which kind of information it is possible to gather with these methodologies while the persons are watching marketing relevant stimuli. Such information will be related to the memorization and pleasantness related to such stimuli. We noted that temporal and frequency patterns of brain signals are able to provide possible descriptors conveying information about the cognitive and emotional processes in subjects observing commercial advertisements. These information could be unobtainable through common tools used in standard marketing research. We also show an example of how an EEG methodology could be used to analyze cultural differences between fruition of video commercials of carbonated beverages in Western and Eastern countries.

On the Use of EEG or MEG Brain Imaging Tools in Neuromarketing Research

PubMed Central

Vecchiato, Giovanni; Astolfi, Laura; De Vico Fallani, Fabrizio; Toppi, Jlenia; Aloise, Fabio; Bez, Francesco; Wei, Daming; Kong, Wanzeng; Dai, Jounging; Cincotti, Febo; Mattia, Donatella; Babiloni, Fabio

2011-01-01

Here we present an overview of some published papers of interest for the marketing research employing electroencephalogram (EEG) and magnetoencephalogram (MEG) methods. The interest for these methodologies relies in their high-temporal resolution as opposed to the investigation of such problem with the functional Magnetic Resonance Imaging (fMRI) methodology, also largely used in the marketing research. In addition, EEG and MEG technologies have greatly improved their spatial resolution in the last decades with the introduction of advanced signal processing methodologies. By presenting data gathered through MEG and high resolution EEG we will show which kind of information it is possible to gather with these methodologies while the persons are watching marketing relevant stimuli. Such information will be related to the memorization and pleasantness related to such stimuli. We noted that temporal and frequency patterns of brain signals are able to provide possible descriptors conveying information about the cognitive and emotional processes in subjects observing commercial advertisements. These information could be unobtainable through common tools used in standard marketing research. We also show an example of how an EEG methodology could be used to analyze cultural differences between fruition of video commercials of carbonated beverages in Western and Eastern countries. PMID:21960996

Confocal microscopy for astrocyte in vivo imaging: Recycle and reuse in microscopy

PubMed Central

Pérez-Alvarez, Alberto; Araque, Alfonso; Martín, Eduardo D.

2013-01-01

In vivo imaging is one of the ultimate and fundamental approaches for the study of the brain. Two-photon laser scanning microscopy (2PLSM) constitutes the state-of-the-art technique in current neuroscience to address questions regarding brain cell structure, development and function, blood flow regulation and metabolism. This technique evolved from laser scanning confocal microscopy (LSCM), which impacted the field with a major improvement in image resolution of live tissues in the 1980s compared to widefield microscopy. While nowadays some of the unparalleled features of 2PLSM make it the tool of choice for brain studies in vivo, such as the possibility to image deep within a tissue, LSCM can still be useful in this matter. Here we discuss the validity and limitations of LSCM and provide a guide to perform high-resolution in vivo imaging of the brain of live rodents with minimal mechanical disruption employing LSCM. We describe the surgical procedure and experimental setup that allowed us to record intracellular calcium variations in astrocytes evoked by sensory stimulation, and to monitor intact neuronal dendritic spines and astrocytic processes as well as blood vessel dynamics. Therefore, in spite of certain limitations that need to be carefully considered, LSCM constitutes a useful, convenient, and affordable tool for brain studies in vivo. PMID:23658537

A Nested Phosphorus and Proton Coil Array for Brain Magnetic Resonance Imaging and Spectroscopy

PubMed Central

Brown, Ryan; Lakshmanan, Karthik; Madelin, Guillaume; Parasoglou, Prodromos

2015-01-01

A dual-nuclei radiofrequency coil array was constructed for phosphorus and proton magnetic resonance imaging and spectroscopy of the human brain at 7 Tesla. An eight-channel transceive degenerate birdcage phosphorus module was implemented to provide whole-brain coverage and significant sensitivity improvement over a standard dual-tuned loop coil. A nested eight-channel proton module provided adequate sensitivity for anatomical localization without substantially sacrificing performance on the phosphorus module. The developed array enabled phosphorus spectroscopy, a saturation transfer technique to calculate the global creatine kinase forward reaction rate, and single-metabolite whole-brain imaging with 1.4 cm nominal isotropic resolution in 15 min (2.3 cm actual resolution), while additionally enabling 1 mm isotropic proton imaging. This study demonstrates that a multi-channel array can be utilized for phosphorus and proton applications with improved coverage and/or sensitivity over traditional single-channel coils. The efficient multi-channel coil array, time-efficient pulse sequences, and the enhanced signal strength available at ultra-high fields can be combined to allow volumetric assessment of the brain and could provide new insights into the underlying energy metabolism impairment in several neurodegenerative conditions, such as Alzheimer’s and Parkinson’s diseases, as well as mental disorders such as schizophrenia. PMID:26375209

A nested phosphorus and proton coil array for brain magnetic resonance imaging and spectroscopy.

PubMed

Brown, Ryan; Lakshmanan, Karthik; Madelin, Guillaume; Parasoglou, Prodromos

2016-01-01

A dual-nuclei radiofrequency coil array was constructed for phosphorus and proton magnetic resonance imaging and spectroscopy of the human brain at 7T. An eight-channel transceive degenerate birdcage phosphorus module was implemented to provide whole-brain coverage and significant sensitivity improvement over a standard dual-tuned loop coil. A nested eight-channel proton module provided adequate sensitivity for anatomical localization without substantially sacrificing performance on the phosphorus module. The developed array enabled phosphorus spectroscopy, a saturation transfer technique to calculate the global creatine kinase forward reaction rate, and single-metabolite whole-brain imaging with 1.4cm nominal isotropic resolution in 15min (2.3cm actual resolution), while additionally enabling 1mm isotropic proton imaging. This study demonstrates that a multi-channel array can be utilized for phosphorus and proton applications with improved coverage and/or sensitivity over traditional single-channel coils. The efficient multi-channel coil array, time-efficient pulse sequences, and the enhanced signal strength available at ultra-high fields can be combined to allow volumetric assessment of the brain and could provide new insights into the underlying energy metabolism impairment in several neurodegenerative conditions, such as Alzheimer's and Parkinson's diseases, as well as mental disorders such as schizophrenia. Copyright © 2015 Elsevier Inc. All rights reserved.

Fetal brain volumetry through MRI volumetric reconstruction and segmentation

PubMed Central

Estroff, Judy A.; Barnewolt, Carol E.; Connolly, Susan A.; Warfield, Simon K.

2013-01-01

Purpose Fetal MRI volumetry is a useful technique but it is limited by a dependency upon motion-free scans, tedious manual segmentation, and spatial inaccuracy due to thick-slice scans. An image processing pipeline that addresses these limitations was developed and tested. Materials and methods The principal sequences acquired in fetal MRI clinical practice are multiple orthogonal single-shot fast spin echo scans. State-of-the-art image processing techniques were used for inter-slice motion correction and super-resolution reconstruction of high-resolution volumetric images from these scans. The reconstructed volume images were processed with intensity non-uniformity correction and the fetal brain extracted by using supervised automated segmentation. Results Reconstruction, segmentation and volumetry of the fetal brains for a cohort of twenty-five clinically acquired fetal MRI scans was done. Performance metrics for volume reconstruction, segmentation and volumetry were determined by comparing to manual tracings in five randomly chosen cases. Finally, analysis of the fetal brain and parenchymal volumes was performed based on the gestational age of the fetuses. Conclusion The image processing pipeline developed in this study enables volume rendering and accurate fetal brain volumetry by addressing the limitations of current volumetry techniques, which include dependency on motion-free scans, manual segmentation, and inaccurate thick-slice interpolation. PMID:20625848

Gene expression profiles of brain endothelial cells during embryonic development at bulk and single-cell levels.

PubMed

Hupe, Mike; Li, Minerva Xueting; Kneitz, Susanne; Davydova, Daria; Yokota, Chika; Kele-Olovsson, Julianna; Hot, Belma; Stenman, Jan M; Gessler, Manfred

2017-07-11

The blood-brain barrier is a dynamic interface that separates the brain from the circulatory system, and it is formed by highly specialized endothelial cells. To explore the molecular mechanisms defining the unique nature of vascular development and differentiation in the brain, we generated high-resolution gene expression profiles of mouse embryonic brain endothelial cells using translating ribosome affinity purification and single-cell RNA sequencing. We compared the brain vascular translatome with the vascular translatomes of other organs and analyzed the vascular translatomes of the brain at different time points during embryonic development. Because canonical Wnt signaling is implicated in the formation of the blood-brain barrier, we also compared the brain endothelial translatome of wild-type mice with that of mice lacking the transcriptional cofactor β-catenin ( Ctnnb1 ). Our analysis revealed extensive molecular changes during the embryonic development of the brain endothelium. We identified genes encoding brain endothelium-specific transcription factors ( Foxf2 , Foxl2 , Foxq1 , Lef1 , Ppard , Zfp551 , and Zic3 ) that are associated with maturation of the blood-brain barrier and act downstream of the Wnt-β-catenin signaling pathway. Profiling of individual brain endothelial cells revealed substantial heterogeneity in the population. Nevertheless, the high abundance of Foxf2 , Foxq1 , Ppard , or Zic3 transcripts correlated with the increased expression of genes encoding markers of brain endothelial cell differentiation. Expression of Foxf2 and Zic3 in human umbilical vein endothelial cells induced the production of blood-brain barrier differentiation markers. This comprehensive data set may help to improve the engineering of in vitro blood-brain barrier models. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Listening to Brain Microcircuits for Interfacing With External World—Progress in Wireless Implantable Microelectronic Neuroengineering Devices

PubMed Central

Nurmikko, Arto V.; Donoghue, John P.; Hochberg, Leigh R.; Patterson, William R.; Song, Yoon-Kyu; Bull, Christopher W.; Borton, David A.; Laiwalla, Farah; Park, Sunmee; Ming, Yin; Aceros, Juan

2011-01-01

Acquiring neural signals at high spatial and temporal resolution directly from brain microcircuits and decoding their activity to interpret commands and/or prior planning activity, such as motion of an arm or a leg, is a prime goal of modern neurotechnology. Its practical aims include assistive devices for subjects whose normal neural information pathways are not functioning due to physical damage or disease. On the fundamental side, researchers are striving to decipher the code of multiple neural microcircuits which collectively make up nature’s amazing computing machine, the brain. By implanting biocompatible neural sensor probes directly into the brain, in the form of microelectrode arrays, it is now possible to extract information from interacting populations of neural cells with spatial and temporal resolution at the single cell level. With parallel advances in application of statistical and mathematical techniques tools for deciphering the neural code, extracted populations or correlated neurons, significant understanding has been achieved of those brain commands that control, e.g., the motion of an arm in a primate (monkey or a human subject). These developments are accelerating the work on neural prosthetics where brain derived signals may be employed to bypass, e.g., an injured spinal cord. One key element in achieving the goals for practical and versatile neural prostheses is the development of fully implantable wireless microelectronic “brain-interfaces” within the body, a point of special emphasis of this paper. PMID:21654935

Super Resolution Imaging of Genetically Labeled Synapses in Drosophila Brain Tissue

PubMed Central

Spühler, Isabelle A.; Conley, Gaurasundar M.; Scheffold, Frank; Sprecher, Simon G.

2016-01-01

Understanding synaptic connectivity and plasticity within brain circuits and their relationship to learning and behavior is a fundamental quest in neuroscience. Visualizing the fine details of synapses using optical microscopy remains however a major technical challenge. Super resolution microscopy opens the possibility to reveal molecular features of synapses beyond the diffraction limit. With direct stochastic optical reconstruction microscopy, dSTORM, we image synaptic proteins in the brain tissue of the fruit fly, Drosophila melanogaster. Super resolution imaging of brain tissue harbors difficulties due to light scattering and the density of signals. In order to reduce out of focus signal, we take advantage of the genetic tools available in the Drosophila and have fluorescently tagged synaptic proteins expressed in only a small number of neurons. These neurons form synapses within the calyx of the mushroom body, a distinct brain region involved in associative memory formation. Our results show that super resolution microscopy, in combination with genetically labeled synaptic proteins, is a powerful tool to investigate synapses in a quantitative fashion providing an entry point for studies on synaptic plasticity during learning and memory formation. PMID:27303270

Super Resolution Imaging of Genetically Labeled Synapses in Drosophila Brain Tissue.

PubMed

Spühler, Isabelle A; Conley, Gaurasundar M; Scheffold, Frank; Sprecher, Simon G

2016-01-01

Understanding synaptic connectivity and plasticity within brain circuits and their relationship to learning and behavior is a fundamental quest in neuroscience. Visualizing the fine details of synapses using optical microscopy remains however a major technical challenge. Super resolution microscopy opens the possibility to reveal molecular features of synapses beyond the diffraction limit. With direct stochastic optical reconstruction microscopy, dSTORM, we image synaptic proteins in the brain tissue of the fruit fly, Drosophila melanogaster. Super resolution imaging of brain tissue harbors difficulties due to light scattering and the density of signals. In order to reduce out of focus signal, we take advantage of the genetic tools available in the Drosophila and have fluorescently tagged synaptic proteins expressed in only a small number of neurons. These neurons form synapses within the calyx of the mushroom body, a distinct brain region involved in associative memory formation. Our results show that super resolution microscopy, in combination with genetically labeled synaptic proteins, is a powerful tool to investigate synapses in a quantitative fashion providing an entry point for studies on synaptic plasticity during learning and memory formation.

Optical Probes for Neurobiological Sensing and Imaging.

PubMed

Kim, Eric H; Chin, Gregory; Rong, Guoxin; Poskanzer, Kira E; Clark, Heather A

2018-05-15

Fluorescent nanosensors and molecular probes are next-generation tools for imaging chemical signaling inside and between cells. Electrophysiology has long been considered the gold standard in elucidating neural dynamics with high temporal resolution and precision, particularly on the single-cell level. However, electrode-based techniques face challenges in illuminating the specific chemicals involved in neural cell activation with adequate spatial information. Measuring chemical dynamics is of fundamental importance to better understand synergistic interactions between neurons as well as interactions between neurons and non-neuronal cells. Over the past decade, significant technological advances in optical probes and imaging methods have enabled entirely new possibilities for studying neural cells and circuits at the chemical level. These optical imaging modalities have shown promise for combining chemical, temporal, and spatial information. This potential makes them ideal candidates to unravel the complex neural interactions at multiple scales in the brain, which could be complemented by traditional electrophysiological methods to obtain a full spatiotemporal picture of neurochemical dynamics. Despite the potential, only a handful of probe candidates have been utilized to provide detailed chemical information in the brain. To date, most live imaging and chemical mapping studies rely on fluorescent molecular indicators to report intracellular calcium (Ca 2+ ) dynamics, which correlates with neuronal activity. Methodological advances for monitoring a full array of chemicals in the brain with improved spatial, temporal, and chemical resolution will thus enable mapping of neurochemical circuits with finer precision. On the basis of numerous studies in this exciting field, we review the current efforts to develop and apply a palette of optical probes and nanosensors for chemical sensing in the brain. There is a strong impetus to further develop technologies capable of probing entire neurobiological units with high spatiotemporal resolution. Thus, we introduce selected applications for ion and neurotransmitter detection to investigate both neurons and non-neuronal brain cells. We focus on families of optical probes because of their ability to sense a wide array of molecules and convey spatial information with minimal damage to tissue. We start with a discussion of currently available molecular probes, highlight recent advances in genetically modified fluorescent probes for ions and small molecules, and end with the latest research in nanosensors for biological imaging. Customizable, nanoscale optical sensors that accurately and dynamically monitor the local environment with high spatiotemporal resolution could lead to not only new insights into the function of all cell types but also a broader understanding of how diverse neural signaling systems act in conjunction with neighboring cells in a spatially relevant manner.

Automated brain tissue and myelin volumetry based on quantitative MR imaging with various in-plane resolutions.

PubMed

Andica, C; Hagiwara, A; Hori, M; Nakazawa, M; Goto, M; Koshino, S; Kamagata, K; Kumamaru, K K; Aoki, S

2018-05-01

Segmented brain tissue and myelin volumes can now be automatically calculated using dedicated software (SyMRI), which is based on quantification of R 1 and R 2 relaxation rates and proton density. The aim of this study was to determine the validity of SyMRI brain tissue and myelin volumetry using various in-plane resolutions. We scanned 10 healthy subjects on a 1.5T MR scanner with in-plane resolutions of 0.8, 2.0 and 3.0mm. Two scans were performed for each resolution. The acquisition time was 7-min and 24-sec for 0.8mm, 3-min and 9-sec for 2.0mm and 1-min and 56-sec for 3.0mm resolutions. The volumes of white matter (WM), gray matter (GM), cerebrospinal fluid (CSF), non-WM/GM/CSF (NoN), brain parenchymal volume (BPV), intracranial volume (ICV) and myelin were compared between in-plane resolutions. Repeatability for each resolution was then analyzed. No significant differences in volumes measured were found between the different in-plane resolutions, except for NoN between 0.8mm and 2.0mm and between 2.0mm and 3.0mm. The repeatability error value for the WM, GM, CSF, NoN, BPV and myelin volumes relative to ICV was 0.97%, 1.01%, 0.65%, 0.86%, 1.06% and 0.25% in 0.8mm; 1.22%, 1.36%, 0.73%, 0.37%, 1.18% and 0.35% in 2.0mm and 1.18%, 1.02%, 0.96%, 0.45%, 1.36%, and 0.28% in 3.0mm resolutions. SyMRI brain tissue and myelin volumetry with low in-plane resolution and short acquisition times is robust and has a good repeatability so could be useful for follow-up studies. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

High-resolution brain SPECT imaging by combination of parallel and tilted detector heads.

PubMed

Suzuki, Atsuro; Takeuchi, Wataru; Ishitsu, Takafumi; Morimoto, Yuichi; Kobashi, Keiji; Ueno, Yuichiro

2015-10-01

To improve the spatial resolution of brain single-photon emission computed tomography (SPECT), we propose a new brain SPECT system in which the detector heads are tilted towards the rotation axis so that they are closer to the brain. In addition, parallel detector heads are used to obtain the complete projection data set. We evaluated this parallel and tilted detector head system (PT-SPECT) in simulations. In the simulation study, the tilt angle of the detector heads relative to the axis was 45°. The distance from the collimator surface of the parallel detector heads to the axis was 130 mm. The distance from the collimator surface of the tilted detector heads to the origin on the axis was 110 mm. A CdTe semiconductor panel with a 1.4 mm detector pitch and a parallel-hole collimator were employed in both types of detector head. A line source phantom, cold-rod brain-shaped phantom, and cerebral blood flow phantom were evaluated. The projection data were generated by forward-projection of the phantom images using physics models, and Poisson noise at clinical levels was applied to the projection data. The ordered-subsets expectation maximization algorithm with physics models was used. We also evaluated conventional SPECT using four parallel detector heads for the sake of comparison. The evaluation of the line source phantom showed that the transaxial FWHM in the central slice for conventional SPECT ranged from 6.1 to 8.5 mm, while that for PT-SPECT ranged from 5.3 to 6.9 mm. The cold-rod brain-shaped phantom image showed that conventional SPECT could visualize up to 8-mm-diameter rods. By contrast, PT-SPECT could visualize up to 6-mm-diameter rods in upper slices of a cerebrum. The cerebral blood flow phantom image showed that the PT-SPECT system provided higher resolution at the thalamus and caudate nucleus as well as at the longitudinal fissure of the cerebrum compared with conventional SPECT. PT-SPECT provides improved image resolution at not only upper but also at central slices of the cerebrum.

Multiphoton Intravital Calcium Imaging.

PubMed

Cheetham, Claire E J

2018-06-26

Multiphoton intravital calcium imaging is a powerful technique that enables high-resolution longitudinal monitoring of cellular and subcellular activity hundreds of microns deep in the living organism. This unit addresses the application of 2-photon microscopy to imaging of genetically encoded calcium indicators (GECIs) in the mouse brain. The protocols in this unit enable real-time intravital imaging of intracellular calcium concentration simultaneously in hundreds of neurons, or at the resolution of single synapses, as mice respond to sensory stimuli or perform behavioral tasks. Protocols are presented for implantation of a cranial imaging window to provide optical access to the brain and for 2-photon image acquisition. Protocols for implantation of both open skull and thinned skull windows for single or multi-session imaging are described. © 2018 by John Wiley & Sons, Inc. © 2018 John Wiley & Sons, Inc.

Graph-based network analysis of resting-state functional MRI.

PubMed

Wang, Jinhui; Zuo, Xinian; He, Yong

2010-01-01

In the past decade, resting-state functional MRI (R-fMRI) measures of brain activity have attracted considerable attention. Based on changes in the blood oxygen level-dependent signal, R-fMRI offers a novel way to assess the brain's spontaneous or intrinsic (i.e., task-free) activity with both high spatial and temporal resolutions. The properties of both the intra- and inter-regional connectivity of resting-state brain activity have been well documented, promoting our understanding of the brain as a complex network. Specifically, the topological organization of brain networks has been recently studied with graph theory. In this review, we will summarize the recent advances in graph-based brain network analyses of R-fMRI signals, both in typical and atypical populations. Application of these approaches to R-fMRI data has demonstrated non-trivial topological properties of functional networks in the human brain. Among these is the knowledge that the brain's intrinsic activity is organized as a small-world, highly efficient network, with significant modularity and highly connected hub regions. These network properties have also been found to change throughout normal development, aging, and in various pathological conditions. The literature reviewed here suggests that graph-based network analyses are capable of uncovering system-level changes associated with different processes in the resting brain, which could provide novel insights into the understanding of the underlying physiological mechanisms of brain function. We also highlight several potential research topics in the future.

Listening to Brain Microcircuits for Interfacing With External World-Progress in Wireless Implantable Microelectronic Neuroengineering Devices: Experimental systems are described for electrical recording in the brain using multiple microelectrodes and short range implantable or wearable broadcasting units.

PubMed

Nurmikko, Arto V; Donoghue, John P; Hochberg, Leigh R; Patterson, William R; Song, Yoon-Kyu; Bull, Christopher W; Borton, David A; Laiwalla, Farah; Park, Sunmee; Ming, Yin; Aceros, Juan

2010-01-01

Acquiring neural signals at high spatial and temporal resolution directly from brain microcircuits and decoding their activity to interpret commands and/or prior planning activity, such as motion of an arm or a leg, is a prime goal of modern neurotechnology. Its practical aims include assistive devices for subjects whose normal neural information pathways are not functioning due to physical damage or disease. On the fundamental side, researchers are striving to decipher the code of multiple neural microcircuits which collectively make up nature's amazing computing machine, the brain. By implanting biocompatible neural sensor probes directly into the brain, in the form of microelectrode arrays, it is now possible to extract information from interacting populations of neural cells with spatial and temporal resolution at the single cell level. With parallel advances in application of statistical and mathematical techniques tools for deciphering the neural code, extracted populations or correlated neurons, significant understanding has been achieved of those brain commands that control, e.g., the motion of an arm in a primate (monkey or a human subject). These developments are accelerating the work on neural prosthetics where brain derived signals may be employed to bypass, e.g., an injured spinal cord. One key element in achieving the goals for practical and versatile neural prostheses is the development of fully implantable wireless microelectronic "brain-interfaces" within the body, a point of special emphasis of this paper.

Simulation of High-Resolution Magnetic Resonance Images on the IBM Blue Gene/L Supercomputer Using SIMRI

DOE PAGES

Baum, K. G.; Menezes, G.; Helguera, M.

2011-01-01

Medical imaging system simulators are tools that provide a means to evaluate system architecture and create artificial image sets that are appropriate for specific applications. We have modified SIMRI, a Bloch equation-based magnetic resonance image simulator, in order to successfully generate high-resolution 3D MR images of the Montreal brain phantom using Blue Gene/L systems. Results show that redistribution of the workload allows an anatomically accurate 256 3 voxel spin-echo simulation in less than 5 hours when executed on an 8192-node partition of a Blue Gene/L system.

Simulation of High-Resolution Magnetic Resonance Images on the IBM Blue Gene/L Supercomputer Using SIMRI.

PubMed

Baum, K G; Menezes, G; Helguera, M

2011-01-01

Medical imaging system simulators are tools that provide a means to evaluate system architecture and create artificial image sets that are appropriate for specific applications. We have modified SIMRI, a Bloch equation-based magnetic resonance image simulator, in order to successfully generate high-resolution 3D MR images of the Montreal brain phantom using Blue Gene/L systems. Results show that redistribution of the workload allows an anatomically accurate 256(3) voxel spin-echo simulation in less than 5 hours when executed on an 8192-node partition of a Blue Gene/L system.

A minimally invasive displacement sensor for measuring brain micromotion in 3D with nanometer scale resolution.

PubMed

Vähäsöyrinki, Mikko; Tuukkanen, Tuomas; Sorvoja, Hannu; Pudas, Marko

2009-06-15

Electrophysiological recordings from a single or population of neurons are currently the standard method for investigating neural mechanisms with high spatio-temporal resolution. It is often difficult or even impossible to obtain stable recordings because of brain movements generated by the cardiac and respiratory functions and/or motor activity. An alternative approach to extensive surgical procedures aimed to reduce these movements would be to develop a control system capable of compensating the relative movement between the recording site and the electrode. As a first step towards such a system, an accurate method capable of measuring brain micromotion, preferably in 3D, in a non-invasive manner is required. A wide variety of technical solutions exist for displacement measurement. However, increased sensitivity in the measurement is often accompanied by strict limitations to sensor handling, implementation and external environment. In addition, majority of the current methods are limited to measurement along only one axis. We present a novel, minimally invasive, 3D displacement sensor with displacement resolution exceeding 70 nm along each axis. The sensor is based on optoelectronic detection of movements of a spring-like element with three degrees of freedom. It is remarkably compact with needle-like probe and can be packaged to withstand considerable mishandling, which allow easy implementation to existing measurement systems. We quantify the sensor performance and demonstrate its capabilities with an in vivo measurement of blowfly brain micromotion in a preparation commonly used for electrophysiology.

Dimensionless, Scale Invariant, Edge Weight Metric for the Study of Complex Structural Networks

PubMed Central

Colon-Perez, Luis M.; Spindler, Caitlin; Goicochea, Shelby; Triplett, William; Parekh, Mansi; Montie, Eric; Carney, Paul R.; Price, Catherine; Mareci, Thomas H.

2015-01-01

High spatial and angular resolution diffusion weighted imaging (DWI) with network analysis provides a unique framework for the study of brain structure in vivo. DWI-derived brain connectivity patterns are best characterized with graph theory using an edge weight to quantify the strength of white matter connections between gray matter nodes. Here a dimensionless, scale-invariant edge weight is introduced to measure node connectivity. This edge weight metric provides reasonable and consistent values over any size scale (e.g. rodents to humans) used to quantify the strength of connection. Firstly, simulations were used to assess the effects of tractography seed point density and random errors in the estimated fiber orientations; with sufficient signal-to-noise ratio (SNR), edge weight estimates improve as the seed density increases. Secondly to evaluate the application of the edge weight in the human brain, ten repeated measures of DWI in the same healthy human subject were analyzed. Mean edge weight values within the cingulum and corpus callosum were consistent and showed low variability. Thirdly, using excised rat brains to study the effects of spatial resolution, the weight of edges connecting major structures in the temporal lobe were used to characterize connectivity in this local network. The results indicate that with adequate resolution and SNR, connections between network nodes are characterized well by this edge weight metric. Therefore this new dimensionless, scale-invariant edge weight metric provides a robust measure of network connectivity that can be applied in any size regime. PMID:26173147

Dimensionless, Scale Invariant, Edge Weight Metric for the Study of Complex Structural Networks.

PubMed

Colon-Perez, Luis M; Spindler, Caitlin; Goicochea, Shelby; Triplett, William; Parekh, Mansi; Montie, Eric; Carney, Paul R; Price, Catherine; Mareci, Thomas H

2015-01-01

High spatial and angular resolution diffusion weighted imaging (DWI) with network analysis provides a unique framework for the study of brain structure in vivo. DWI-derived brain connectivity patterns are best characterized with graph theory using an edge weight to quantify the strength of white matter connections between gray matter nodes. Here a dimensionless, scale-invariant edge weight is introduced to measure node connectivity. This edge weight metric provides reasonable and consistent values over any size scale (e.g. rodents to humans) used to quantify the strength of connection. Firstly, simulations were used to assess the effects of tractography seed point density and random errors in the estimated fiber orientations; with sufficient signal-to-noise ratio (SNR), edge weight estimates improve as the seed density increases. Secondly to evaluate the application of the edge weight in the human brain, ten repeated measures of DWI in the same healthy human subject were analyzed. Mean edge weight values within the cingulum and corpus callosum were consistent and showed low variability. Thirdly, using excised rat brains to study the effects of spatial resolution, the weight of edges connecting major structures in the temporal lobe were used to characterize connectivity in this local network. The results indicate that with adequate resolution and SNR, connections between network nodes are characterized well by this edge weight metric. Therefore this new dimensionless, scale-invariant edge weight metric provides a robust measure of network connectivity that can be applied in any size regime.

Distinct prediction errors in mesostriatal circuits of the human brain mediate learning about the values of both states and actions: evidence from high-resolution fMRI.

PubMed

Colas, Jaron T; Pauli, Wolfgang M; Larsen, Tobias; Tyszka, J Michael; O'Doherty, John P

2017-10-01

Prediction-error signals consistent with formal models of "reinforcement learning" (RL) have repeatedly been found within dopaminergic nuclei of the midbrain and dopaminoceptive areas of the striatum. However, the precise form of the RL algorithms implemented in the human brain is not yet well determined. Here, we created a novel paradigm optimized to dissociate the subtypes of reward-prediction errors that function as the key computational signatures of two distinct classes of RL models-namely, "actor/critic" models and action-value-learning models (e.g., the Q-learning model). The state-value-prediction error (SVPE), which is independent of actions, is a hallmark of the actor/critic architecture, whereas the action-value-prediction error (AVPE) is the distinguishing feature of action-value-learning algorithms. To test for the presence of these prediction-error signals in the brain, we scanned human participants with a high-resolution functional magnetic-resonance imaging (fMRI) protocol optimized to enable measurement of neural activity in the dopaminergic midbrain as well as the striatal areas to which it projects. In keeping with the actor/critic model, the SVPE signal was detected in the substantia nigra. The SVPE was also clearly present in both the ventral striatum and the dorsal striatum. However, alongside these purely state-value-based computations we also found evidence for AVPE signals throughout the striatum. These high-resolution fMRI findings suggest that model-free aspects of reward learning in humans can be explained algorithmically with RL in terms of an actor/critic mechanism operating in parallel with a system for more direct action-value learning.

Integration of ultra-high field MRI and histology for connectome based research of brain disorders

PubMed Central

Yang, Shan; Yang, Zhengyi; Fischer, Karin; Zhong, Kai; Stadler, Jörg; Godenschweger, Frank; Steiner, Johann; Heinze, Hans-Jochen; Bernstein, Hans-Gert; Bogerts, Bernhard; Mawrin, Christian; Reutens, David C.; Speck, Oliver; Walter, Martin

2013-01-01

Ultra-high field magnetic resonance imaging (MRI) became increasingly relevant for in vivo neuroscientific research because of improved spatial resolutions. However, this is still the unchallenged domain of histological studies, which long played an important role in the investigation of neuropsychiatric disorders. While the field of biological psychiatry strongly advanced on macroscopic levels, current developments are rediscovering the richness of immunohistological information when attempting a multi-level systematic approach to brain function and dysfunction. For most studies, histology sections lost information on three-dimensional reconstructions. Translating histological sections to 3D-volumes would thus not only allow for multi-stain and multi-subject alignment in post mortem data, but also provide a crucial step in big data initiatives involving the network analyses currently performed with in vivo MRI. We therefore investigated potential pitfalls during integration of MR and histological information where no additional blockface information is available. We demonstrated that strengths and requirements from both methods can be effectively combined at a spatial resolution of 200 μm. However, the success of this approach is heavily dependent on choices of hardware, sequence and reconstruction. We provide a fully automated pipeline that optimizes histological 3D reconstructions, providing a potentially powerful solution not only for primary human post mortem research institutions in neuropsychiatric research, but also to help alleviate the massive workloads in neuroanatomical atlas initiatives. We further demonstrate (for the first time) the feasibility and quality of ultra-high spatial resolution (150 μm isotopic) imaging of the entire human brain MRI at 7T, offering new opportunities for analyses on MR-derived information. PMID:24098272

Distinct prediction errors in mesostriatal circuits of the human brain mediate learning about the values of both states and actions: evidence from high-resolution fMRI

PubMed Central

Pauli, Wolfgang M.; Larsen, Tobias; Tyszka, J. Michael; O’Doherty, John P.

2017-01-01

Prediction-error signals consistent with formal models of “reinforcement learning” (RL) have repeatedly been found within dopaminergic nuclei of the midbrain and dopaminoceptive areas of the striatum. However, the precise form of the RL algorithms implemented in the human brain is not yet well determined. Here, we created a novel paradigm optimized to dissociate the subtypes of reward-prediction errors that function as the key computational signatures of two distinct classes of RL models—namely, “actor/critic” models and action-value-learning models (e.g., the Q-learning model). The state-value-prediction error (SVPE), which is independent of actions, is a hallmark of the actor/critic architecture, whereas the action-value-prediction error (AVPE) is the distinguishing feature of action-value-learning algorithms. To test for the presence of these prediction-error signals in the brain, we scanned human participants with a high-resolution functional magnetic-resonance imaging (fMRI) protocol optimized to enable measurement of neural activity in the dopaminergic midbrain as well as the striatal areas to which it projects. In keeping with the actor/critic model, the SVPE signal was detected in the substantia nigra. The SVPE was also clearly present in both the ventral striatum and the dorsal striatum. However, alongside these purely state-value-based computations we also found evidence for AVPE signals throughout the striatum. These high-resolution fMRI findings suggest that model-free aspects of reward learning in humans can be explained algorithmically with RL in terms of an actor/critic mechanism operating in parallel with a system for more direct action-value learning. PMID:29049406

Simulating the Effect of Spectroscopic MRI as a Metric for Radiation Therapy Planning in Patients with Glioblastoma

PubMed Central

Cordova, J. Scott; Kandula, Shravan; Gurbani, Saumya; Zhong, Jim; Tejani, Mital; Kayode, Oluwatosin; Patel, Kirtesh; Prabhu, Roshan; Schreibmann, Eduard; Crocker, Ian; Holder, Chad A.; Shim, Hyunsuk; Shu, Hui-Kuo

2017-01-01

Due to glioblastoma’s infiltrative nature, an optimal radiation therapy (RT) plan requires targeting infiltration not identified by anatomical magnetic resonance imaging (MRI). Here, high-resolution, whole-brain spectroscopic MRI (sMRI) is used to describe tumor infiltration alongside anatomical MRI and simulate the degree to which it modifies RT target planning. In 11 patients with glioblastoma, data from preRT sMRI scans were processed to give high-resolution, whole-brain metabolite maps normalized by contralateral white matter. Maps depicting choline to N-Acetylaspartate (Cho/NAA) ratios were registered to contrast-enhanced T1-weighted RT planning MRI for each patient. Volumes depicting metabolic abnormalities (1.5−, 1.75−, and 2.0-fold increases in Cho/NAA ratios) were compared with conventional target volumes and contrast-enhancing tumor at recurrence. sMRI-modified RT plans were generated to evaluate target volume coverage and organ-at-risk dose constraints. Conventional clinical target volumes and Cho/NAA abnormalities identified significantly different regions of microscopic infiltration with substantial Cho/NAA abnormalities falling outside of the conventional 60 Gy isodose line (41.1, 22.2, and 12.7 cm3, respectively). Clinical target volumes using Cho/NAA thresholds exhibited significantly higher coverage of contrast enhancement at recurrence on average (92.4%, 90.5%, and 88.6%, respectively) than conventional plans (82.5%). sMRI-based plans targeting tumor infiltration met planning objectives in all cases with no significant change in target coverage. In 2 cases, the sMRI-modified plan exhibited better coverage of contrast-enhancing tumor at recurrence than the original plan. Integration of the high-resolution, whole-brain sMRI into RT planning is feasible, resulting in RT target volumes that can effectively target tumor infiltration while adhering to conventional constraints. PMID:28105468

A highly accurate symmetric optical flow based high-dimensional nonlinear spatial normalization of brain images.

PubMed

Wen, Ying; Hou, Lili; He, Lianghua; Peterson, Bradley S; Xu, Dongrong

2015-05-01

Spatial normalization plays a key role in voxel-based analyses of brain images. We propose a highly accurate algorithm for high-dimensional spatial normalization of brain images based on the technique of symmetric optical flow. We first construct a three dimension optical model with the consistency assumption of intensity and consistency of the gradient of intensity under a constraint of discontinuity-preserving spatio-temporal smoothness. Then, an efficient inverse consistency optical flow is proposed with aims of higher registration accuracy, where the flow is naturally symmetric. By employing a hierarchical strategy ranging from coarse to fine scales of resolution and a method of Euler-Lagrange numerical analysis, our algorithm is capable of registering brain images data. Experiments using both simulated and real datasets demonstrated that the accuracy of our algorithm is not only better than that of those traditional optical flow algorithms, but also comparable to other registration methods used extensively in the medical imaging community. Moreover, our registration algorithm is fully automated, requiring a very limited number of parameters and no manual intervention. Copyright © 2015 Elsevier Inc. All rights reserved.

Bombesin receptors and transplanted stem cells in rat brain: High-resolution scan with 99mTc BN1.1

NASA Astrophysics Data System (ADS)

Scopinaro, F.; Paschali, E.; Di Santo, G.; Antonellis, T.; Massari, R.; Trotta, C.; Gourni, H.; Bouziotis, P.; David, V.; Soluri, A.; Varvarigou, A. D.

2006-12-01

The aim of this work is to detect the presence of transplanted stem cells (TSC) in rat brain with high-resolution (HR) scintigraphy and labelled bombesin (BN). BN is a morphogen for Central Nervous System (CNS) as well as for other organs: CNS-oriented TSC over-express BN Receptors (BNR). BN is also a neurotransmitter and modulates several functions of CNS. 99mTc labelled BN-like peptide scan of CNS is the ideal method to detect growing TSC once knowing normal distribution of BNRs in CNS. HR Planar and single photon emission computerized tomography (SPECT) images of rat brain were performed with new HR detectors (Li-tech, Italy). Pertechnetate, 99mTc HMPAO and the new 99mTc BN1.1 (patented) were i.v. administered in five rats. HR SPECT of 99mTc BN1.1 detected olfactory tract, fronto-lateral cortex, cerebellum, basal ganglia and amygdale. Results of SPECT were confirmed by bio-distribution study performed after autopsy of three of the five rats. The remaining two rats underwent cerebral lesions followed by transplant of TSC. Three months later, HR scintigraphy was repeated and showed images completely different from previous basal study, with hot spot of 99mTc BN1.1 corresponding to the site of TSC transplant. Immuno-histochemistry confirmed the presence of viable TSC. Not only 99mTc BN1.1 HR scan showed viability of transplanted TSC but also the "background brain" was the still now unknown map of BNR in mammalian brain.

Planar implantable sensor for in vivo measurement of cellular oxygen metabolism in brain tissue.

PubMed

Tsytsarev, Vassiliy; Akkentli, Fatih; Pumbo, Elena; Tang, Qinggong; Chen, Yu; Erzurumlu, Reha S; Papkovsky, Dmitri B

2017-04-01

Brain imaging methods are continually improving. Imaging of the cerebral cortex is widely used in both animal experiments and charting human brain function in health and disease. Among the animal models, the rodent cerebral cortex has been widely used because of patterned neural representation of the whiskers on the snout and relative ease of activating cortical tissue with whisker stimulation. We tested a new planar solid-state oxygen sensor comprising a polymeric film with a phosphorescent oxygen-sensitive coating on the working side, to monitor dynamics of oxygen metabolism in the cerebral cortex following sensory stimulation. Sensory stimulation led to changes in oxygenation and deoxygenation processes of activated areas in the barrel cortex. We demonstrate the possibility of dynamic mapping of relative changes in oxygenation in live mouse brain tissue with such a sensor. Oxygenation-based functional magnetic resonance imaging (fMRI) is very effective method for functional brain mapping but have high costs and limited spatial resolution. Optical imaging of intrinsic signal (IOS) does not provide the required sensitivity, and voltage-sensitive dye optical imaging (VSDi) has limited applicability due to significant toxicity of the voltage-sensitive dye. Our planar solid-state oxygen sensor imaging approach circumvents these limitations, providing a simple optical contrast agent with low toxicity and rapid application. The planar solid-state oxygen sensor described here can be used as a tool in visualization and real-time analysis of sensory-evoked neural activity in vivo. Further, this approach allows visualization of local neural activity with high temporal and spatial resolution. Copyright © 2017 Elsevier B.V. All rights reserved.

High slew-rate head-only gradient for improving distortion in echo planar imaging: Preliminary experience.

PubMed

Tan, Ek T; Lee, Seung-Kyun; Weavers, Paul T; Graziani, Dominic; Piel, Joseph E; Shu, Yunhong; Huston, John; Bernstein, Matt A; Foo, Thomas K F

2016-09-01

To investigate the effects on echo planar imaging (EPI) distortion of using high gradient slew rates (SR) of up to 700 T/m/s for in vivo human brain imaging, with a dedicated, head-only gradient coil. Simulation studies were first performed to determine the expected echo spacing and distortion reduction in EPI. A head gradient of 42-cm inner diameter and with asymmetric transverse coils was then installed in a whole-body, conventional 3T magnetic resonance imaging (MRI) system. Human subject imaging was performed on five subjects to determine the effects of EPI on echo spacing and signal dropout at various gradient slew rates. The feasibility of whole-brain imaging at 1.5 mm-isotropic spatial resolution was demonstrated with gradient-echo and spin-echo diffusion-weighted EPI. As compared to a whole-body gradient coil, the EPI echo spacing in the head-only gradient coil was reduced by 48%. Simulation and in vivo results, respectively, showed up to 25-26% and 19% improvement in signal dropout. Whole-brain imaging with EPI at 1.5 mm spatial resolution provided good whole-brain coverage, spatial linearity, and low spatial distortion effects. Our results of human brain imaging with EPI using the compact head gradient coil at slew rates higher than in conventional whole-body MR systems demonstrate substantially improved image distortion, and point to a potential for benefits to non-EPI pulse sequences. J. Magn. Reson. Imaging 2016;44:653-664. © 2016 International Society for Magnetic Resonance in Medicine.

Multi-pinhole collimator design for small-object imaging with SiliSPECT: a high-resolution SPECT

NASA Astrophysics Data System (ADS)

Shokouhi, S.; Metzler, S. D.; Wilson, D. W.; Peterson, T. E.

2009-01-01

We have designed a multi-pinhole collimator for a dual-headed, stationary SPECT system that incorporates high-resolution silicon double-sided strip detectors. The compact camera design of our system enables imaging at source-collimator distances between 20 and 30 mm. Our analytical calculations show that using knife-edge pinholes with small-opening angles or cylindrically shaped pinholes in a focused, multi-pinhole configuration in combination with this camera geometry can generate narrow sensitivity profiles across the field of view that can be useful for imaging small objects at high sensitivity and resolution. The current prototype system uses two collimators each containing 127 cylindrically shaped pinholes that are focused toward a target volume. Our goal is imaging objects such as a mouse brain, which could find potential applications in molecular imaging.

Coronal in vivo forward-imaging of rat brain morphology with an ultra-small optical coherence tomography fiber probe

NASA Astrophysics Data System (ADS)

Xie, Yijing; Bonin, Tim; Löffler, Susanne; Hüttmann, Gereon; Tronnier, Volker; Hofmann, Ulrich G.

2013-02-01

A well-established navigation method is one of the key conditions for successful brain surgery: it should be accurate, safe and online operable. Recent research shows that optical coherence tomography (OCT) is a potential solution for this application by providing a high resolution and small probe dimension. In this study a fiber-based spectral-domain OCT system utilizing a super-luminescent-diode with the center wavelength of 840 nm providing 14.5 μm axial resolution was used. A composite 125 μm diameter detecting probe with a gradient index (GRIN) fiber fused to a single mode fiber was employed. Signals were reconstructed into grayscale images by horizontally aligning A-scans from the same trajectory with different depths. The reconstructed images can display brain morphology along the entire trajectory. For scans of typical white matter, the signals showed a higher reflection of light intensity with lower penetration depth as well as a steeper attenuation rate compared to the scans typical for gray matter. Micro-structures such as axon bundles (70 μm) in the caudate nucleus are visible in the reconstructed images. This study explores the potential of OCT to be a navigation modality in brain surgery.

Aiding the Eye, Watching the Brain: James Weiland, IEEE Fellow, explores the unique challenges of retinal prostheses.

PubMed

Grifantini, Kristina

2017-01-01

The retina is a sophisticated neural network that provides humans with high-resolution vision. And for those who suffer from retinal disease or deterioration, particularly age-related macular degeneration (the leading cause of blindness among people over the age of 50 in the United States), a better understanding of how to stimulate the retina or completely override its path to the area of the brain that processes vision may offer hope to restore sight.

Radiotracers for PETT: new developments and perspectives

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fowler, J.S.; Wolf, A.P.

Radiotracer development with positron emitters has its major focus on problems in the neurosciences. Progress is reviewed for high-level isotope production and labelled precurser synthesis with the medical cyclotron. The study of regional brain glucose metabolism represented the first extension of one of the methods of neurochemical autoradiography to humans and the study of brain protein synthesis and neurotransmitter receptors followed. In a more general sense, one PETT instrumentation will provide resolution in the 5 mm range is already emerging. Research status is reviewed. 103 references. (PSB)

Viewing the functional consequences of traumatic brain injury by using brain SPECT.

PubMed

Pavel, D; Jobe, T; Devore-Best, S; Davis, G; Epstein, P; Sinha, S; Kohn, R; Craita, I; Liu, P; Chang, Y

2006-03-01

High-resolution brain SPECT is increasingly benefiting from improved image processing software and multiple complementary display capabilities. This enables detailed functional mapping of the disturbances in relative perfusion occurring after TBI. The patient population consisted of 26 cases (ages 8-61 years)between 3 months and 6 years after traumatic brain injury.A very strong case can be made for the routine use of Brain SPECT in TBI. Indeed it can provide a detailed evaluation of multiple functional consequences after TBI and is thus capable of supplementing the clinical evaluation and tailoring the therapeutic strategies needed. In so doing it also provides significant additional information beyond that available from MRI/CT. The critical factor for Brain SPECT's clinical relevance is a carefully designed technical protocol, including displays which should enable a comprehensive description of the patterns found, in a user friendly mode.

Neural Correlates of Semantic Prediction and Resolution in Sentence Processing.

PubMed

Grisoni, Luigi; Miller, Tally McCormick; Pulvermüller, Friedemann

2017-05-03

Most brain-imaging studies of language comprehension focus on activity following meaningful stimuli. Testing adult human participants with high-density EEG, we show that, already before the presentation of a critical word, context-induced semantic predictions are reflected by a neurophysiological index, which we therefore call the semantic readiness potential (SRP). The SRP precedes critical words if a previous sentence context constrains the upcoming semantic content (high-constraint contexts), but not in unpredictable (low-constraint) contexts. Specific semantic predictions were indexed by SRP sources within the motor system-in dorsolateral hand motor areas for expected hand-related words (e.g., "write"), but in ventral motor cortex for face-related words ("talk"). Compared with affirmative sentences, negated ones led to medial prefrontal and more widespread motor source activation, the latter being consistent with predictive semantic computation of alternatives to the negated expected concept. Predictive processing of semantic alternatives in negated sentences is further supported by a negative-going event-related potential at ∼400 ms (N400), which showed the typical enhancement to semantically incongruent sentence endings only in high-constraint affirmative contexts, but not to high-constraint negated ones. These brain dynamics reveal the interplay between semantic prediction and resolution (match vs error) processing in sentence understanding. SIGNIFICANCE STATEMENT Most neuroscientists agree on the eminent importance of predictive mechanisms for understanding basic as well as higher brain functions. This contrasts with a sparseness of brain measures that directly reflects specific aspects of prediction, as they are relevant in the processing of language and thought. Here we show that when critical words are strongly expected in their sentence context, a predictive brain response reflects meaning features of these anticipated symbols already before they appear. The granularity of the semantic predictions was so fine grained that the cortical sources in sensorimotor and medial prefrontal cortex even distinguished between predicted face- or hand-related action words (e.g., the words "lick" or "pick") and between affirmative and negated sentence meanings. Copyright © 2017 Grisoni et al.

Neural Correlates of Semantic Prediction and Resolution in Sentence Processing

PubMed Central

2017-01-01

Most brain-imaging studies of language comprehension focus on activity following meaningful stimuli. Testing adult human participants with high-density EEG, we show that, already before the presentation of a critical word, context-induced semantic predictions are reflected by a neurophysiological index, which we therefore call the semantic readiness potential (SRP). The SRP precedes critical words if a previous sentence context constrains the upcoming semantic content (high-constraint contexts), but not in unpredictable (low-constraint) contexts. Specific semantic predictions were indexed by SRP sources within the motor system—in dorsolateral hand motor areas for expected hand-related words (e.g., “write”), but in ventral motor cortex for face-related words (“talk”). Compared with affirmative sentences, negated ones led to medial prefrontal and more widespread motor source activation, the latter being consistent with predictive semantic computation of alternatives to the negated expected concept. Predictive processing of semantic alternatives in negated sentences is further supported by a negative-going event-related potential at ∼400 ms (N400), which showed the typical enhancement to semantically incongruent sentence endings only in high-constraint affirmative contexts, but not to high-constraint negated ones. These brain dynamics reveal the interplay between semantic prediction and resolution (match vs error) processing in sentence understanding. SIGNIFICANCE STATEMENT Most neuroscientists agree on the eminent importance of predictive mechanisms for understanding basic as well as higher brain functions. This contrasts with a sparseness of brain measures that directly reflects specific aspects of prediction, as they are relevant in the processing of language and thought. Here we show that when critical words are strongly expected in their sentence context, a predictive brain response reflects meaning features of these anticipated symbols already before they appear. The granularity of the semantic predictions was so fine grained that the cortical sources in sensorimotor and medial prefrontal cortex even distinguished between predicted face- or hand-related action words (e.g., the words “lick” or “pick”) and between affirmative and negated sentence meanings. PMID:28411271

Detection of white matter injury in concussion using high-definition fiber tractography.

PubMed

Shin, Samuel S; Pathak, Sudhir; Presson, Nora; Bird, William; Wagener, Lauren; Schneider, Walter; Okonkwo, David O; Fernandez-Miranda, Juan C

2014-01-01

Over the last few decades, structural imaging techniques of the human brain have undergone significant strides. High resolution provided by recent developments in magnetic resonance imaging (MRI) allows improved detection of injured regions in patients with moderate-to-severe traumatic brain injury (TBI). In addition, diffusion imaging techniques such as diffusion tensor imaging (DTI) has gained much interest recently due to its possible utility in detecting structural integrity of white matter pathways in mild TBI (mTBI) cases. However, the results from recent DTI studies in mTBI patients remain equivocal. Also, there are important shortcomings for DTI such as limited resolution in areas of multiple crossings and false tract formation. The detection of white matter damage in concussion remains challenging, and development of imaging biomarkers for mTBI is still in great need. In this chapter, we discuss our experience with high-definition fiber tracking (HDFT), a diffusion spectrum imaging-based technique. We also discuss ongoing developments and specific advantages HDFT may offer concussion patients. © 2014 S. Karger AG, Basel.

A high-resolution 7-Tesla fMRI dataset from complex natural stimulation with an audio movie

PubMed Central

Hanke, Michael; Baumgartner, Florian J.; Ibe, Pierre; Kaule, Falko R.; Pollmann, Stefan; Speck, Oliver; Zinke, Wolf; Stadler, Jörg

2014-01-01

Here we present a high-resolution functional magnetic resonance (fMRI) dataset – 20 participants recorded at high field strength (7 Tesla) during prolonged stimulation with an auditory feature film (“Forrest Gump”). In addition, a comprehensive set of auxiliary data (T1w, T2w, DTI, susceptibility-weighted image, angiography) as well as measurements to assess technical and physiological noise components have been acquired. An initial analysis confirms that these data can be used to study common and idiosyncratic brain response patterns to complex auditory stimulation. Among the potential uses of this dataset are the study of auditory attention and cognition, language and music perception, and social perception. The auxiliary measurements enable a large variety of additional analysis strategies that relate functional response patterns to structural properties of the brain. Alongside the acquired data, we provide source code and detailed information on all employed procedures – from stimulus creation to data analysis. In order to facilitate replicative and derived works, only free and open-source software was utilized. PMID:25977761

Quantitative intact specimen magnetic resonance microscopy at 3.0 T.

PubMed

Bath, Kevin G; Voss, Henning U; Jing, Deqiang; Anderson, Stewart; Hempstead, Barbara; Lee, Francis S; Dyke, Jonathan P; Ballon, Douglas J

2009-06-01

In this report, we discuss the application of a methodology for high-contrast, high-resolution magnetic resonance microscopy (MRM) of murine tissue using a 3.0-T imaging system. We employed a threefold strategy that included customized specimen preparation to maximize image contrast, three-dimensional data acquisition to minimize scan time and custom radiofrequency resonator design to maximize signal sensitivity. Images had a resolution of 100 x 78 x 78 microm(3) with a signal-to-noise ratio per voxel greater than 25:1 and excellent contrast-to-noise ratios over a 30-min acquisition. We quantitatively validated the methods through comparisons of neuroanatomy across two lines of genetically engineered mice. Specifically, we were able to detect volumetric differences of as little as 9% between genetically engineered mouse strains in multiple brain regions that were predictive of underlying impairments in brain development. The overall methodology was straightforward to implement and provides ready access to basic MRM at field strengths that are widely available in both the laboratory and the clinic.

Highly Crumpled All-Carbon Transistors for Brain Activity Recording.

PubMed

Yang, Long; Zhao, Yan; Xu, Wenjing; Shi, Enzheng; Wei, Wenjing; Li, Xinming; Cao, Anyuan; Cao, Yanping; Fang, Ying

2017-01-11

Neural probes based on graphene field-effect transistors have been demonstrated. Yet, the minimum detectable signal of graphene transistor-based probes is inversely proportional to the square root of the active graphene area. This fundamentally limits the scaling of graphene transistor-based neural probes for improved spatial resolution in brain activity recording. Here, we address this challenge using highly crumpled all-carbon transistors formed by compressing down to 16% of its initial area. All-carbon transistors, chemically synthesized by seamless integration of graphene channels and hybrid graphene/carbon nanotube electrodes, maintained structural integrity and stable electronic properties under large mechanical deformation, whereas stress-induced cracking and junction failure occurred in conventional graphene/metal transistors. Flexible, highly crumpled all-carbon transistors were further verified for in vivo recording of brain activity in rats. These results highlight the importance of advanced material and device design concepts to make improvements in neuroelectronics.

Complex network analysis of brain functional connectivity under a multi-step cognitive task

NASA Astrophysics Data System (ADS)

Cai, Shi-Min; Chen, Wei; Liu, Dong-Bai; Tang, Ming; Chen, Xun

2017-01-01

Functional brain network has been widely studied to understand the relationship between brain organization and behavior. In this paper, we aim to explore the functional connectivity of brain network under a multi-step cognitive task involving consecutive behaviors, and further understand the effect of behaviors on the brain organization. The functional brain networks are constructed based on a high spatial and temporal resolution fMRI dataset and analyzed via complex network based approach. We find that at voxel level the functional brain network shows robust small-worldness and scale-free characteristics, while its assortativity and rich-club organization are slightly restricted to the order of behaviors performed. More interestingly, the functional connectivity of brain network in activated ROIs strongly correlates with behaviors and is obviously restricted to the order of behaviors performed. These empirical results suggest that the brain organization has the generic properties of small-worldness and scale-free characteristics, and its diverse functional connectivity emerging from activated ROIs is strongly driven by these behavioral activities via the plasticity of brain.

Fiber-bundle-basis sparse reconstruction for high resolution wide-field microendoscopy.

PubMed

Mekhail, Simon Peter; Abudukeyoumu, Nilupaer; Ward, Jonathan; Arbuthnott, Gordon; Chormaic, Síle Nic

2018-04-01

In order to observe deep regions of the brain, we propose the use of a fiber bundle for microendoscopy. Fiber bundles allow for the excitation and collection of fluorescence as well as wide field imaging while remaining largely impervious to image distortions brought on by bending. Furthermore, their thin diameter, from 200-500 µ m, means their impact on living tissue, though not absent, is minimal. Although wide field imaging with a bundle allows for a high temporal resolution since no scanning is involved, the largest criticism of bundle imaging is the drastically lowered spatial resolution. In this paper, we make use of sparsity in the object being imaged to up sample the low resolution images from the fiber bundle with compressive sensing. We take each image in a single shot by using a measurement basis dictated by the quasi-crystalline arrangement of the bundle's cores. We find that this technique allows us to increase the resolution of a typical image taken through a fiber bundle.

Resolution improvement in positron emission tomography using anatomical Magnetic Resonance Imaging.

PubMed

Chu, Yong; Su, Min-Ying; Mandelkern, Mark; Nalcioglu, Orhan

2006-08-01

An ideal imaging system should provide information with high-sensitivity, high spatial, and temporal resolution. Unfortunately, it is not possible to satisfy all of these desired features in a single modality. In this paper, we discuss methods to improve the spatial resolution in positron emission imaging (PET) using a priori information from Magnetic Resonance Imaging (MRI). Our approach uses an image restoration algorithm based on the maximization of mutual information (MMI), which has found significant success for optimizing multimodal image registration. The MMI criterion is used to estimate the parameters in the Sharpness-Constrained Wiener filter. The generated filter is then applied to restore PET images of a realistic digital brain phantom. The resulting restored images show improved resolution and better signal-to-noise ratio compared to the interpolated PET images. We conclude that a Sharpness-Constrained Wiener filter having parameters optimized from a MMI criterion may be useful for restoring spatial resolution in PET based on a priori information from correlated MRI.

Improving axial resolution in confocal microscopy with new high refractive index mounting media.

PubMed

Fouquet, Coralie; Gilles, Jean-François; Heck, Nicolas; Dos Santos, Marc; Schwartzmann, Richard; Cannaya, Vidjeacoumary; Morel, Marie-Pierre; Davidson, Robert Stephen; Trembleau, Alain; Bolte, Susanne

2015-01-01

Resolution, high signal intensity and elevated signal to noise ratio (SNR) are key issues for biologists who aim at studying the localisation of biological structures at the cellular and subcellular levels using confocal microscopy. The resolution required to separate sub-cellular biological structures is often near to the resolving power of the microscope. When optimally used, confocal microscopes may reach resolutions of 180 nm laterally and 500 nm axially, however, axial resolution in depth is often impaired by spherical aberration that may occur due to refractive index mismatches. Spherical aberration results in broadening of the point-spread function (PSF), a decrease in peak signal intensity when imaging in depth and a focal shift that leads to the distortion of the image along the z-axis and thus in a scaling error. In this study, we use the novel mounting medium CFM3 (Citifluor Ltd., UK) with a refractive index of 1.518 to minimize the effects of spherical aberration. This mounting medium is compatible with most common fluorochromes and fluorescent proteins. We compare its performance with established mounting media, harbouring refractive indices below 1.500, by estimating lateral and axial resolution with sub-resolution fluorescent beads. We show furthermore that the use of the high refractive index media renders the tissue transparent and improves considerably the axial resolution and imaging depth in immuno-labelled or fluorescent protein labelled fixed mouse brain tissue. We thus propose to use those novel high refractive index mounting media, whenever optimal axial resolution is required.

Kinetic modeling of the monoamine oxidase B radioligand [¹¹C]SL25.1188 in human brain with high-resolution positron emission tomography.

PubMed

Rusjan, Pablo M; Wilson, Alan A; Miler, Laura; Fan, Ian; Mizrahi, Romina; Houle, Sylvain; Vasdev, Neil; Meyer, Jeffrey H

2014-05-01

This article describes the kinetic modeling of [(11)C]SL25.1188 ([(S)-5-methoxymethyl-3-[6-(4,4,4-trifluorobutoxy)-benzo[d]isoxazol-3-yl]-oxazolidin-2-[(11)C]one]) binding to monoamine oxidase B (MAO-B) in the human brain using high-resolution positron emission tomography (PET). Seven healthy subjects underwent two separate 90- minute PET scans after an intravenous injection of [(11)C]SL25.1188. Complementary arterial blood sampling was acquired. Radioactivity was quickly eliminated from plasma with 80% of parent compound remaining at 90 minutes. Metabolites were more polar than the parent compound. Time-activity curves showed high brain uptake, early peak and washout rate consistent with known regional MAO-B concentration. A two-tissue compartment model (2-TCM) provided better fits to the data than a 1-TCM. Measurement of total distribution volume (VT) showed very good identifiability (based on coefficient of variation (COV)) for all regions of interest (ROIs) (COV(VT)<8%), low between-subject variability (∼20%), and quick temporal convergence (within 5% of final value at 45 minutes). Logan graphical method produces very good estimation of VT. Regional VT highly correlated with previous postmortem report of MAO-B level (r(2)= ≥ 0.9). Specific binding would account from 70% to 90% of VT. Hence, VT measurement of [(11)C]SL25.1(1)88 PET is an excellent estimation of MAO-B concentration.

A Silicon SPECT System for Molecular Imaging of the Mouse Brain.

PubMed

Shokouhi, Sepideh; Fritz, Mark A; McDonald, Benjamin S; Durko, Heather L; Furenlid, Lars R; Wilson, Donald W; Peterson, Todd E

2007-01-01

We previously demonstrated the feasibility of using silicon double-sided strip detectors (DSSDs) for SPECT imaging of the activity distribution of iodine-125 using a 300-micrometer thick detector. Based on this experience, we now have developed fully customized silicon DSSDs and associated readout electronics with the intent of developing a multi-pinhole SPECT system. Each DSSD has a 60.4 mm × 60.4 mm active area and is 1 mm thick. The strip pitch is 59 micrometers, and the readout of the 1024 strips on each side gives rise to a detector with over one million pixels. Combining four high-resolution DSSDs into a SPECT system offers an unprecedented space-bandwidth product for the imaging of single-photon emitters. The system consists of two camera heads with two silicon detectors stacked one behind the other in each head. The collimator has a focused pinhole system with cylindrical-shaped pinholes that are laser-drilled in a 250 μm tungsten plate. The unique ability to collect projection data at two magnifications simultaneously allows for multiplexed data at high resolution to be combined with lower magnification data with little or no multiplexing. With the current multi-pinhole collimator design, our SPECT system will be capable of offering high spatial resolution, sensitivity and angular sampling for small field-of-view applications, such as molecular imaging of the mouse brain.

Design and Characterization of a Microfabricated Hydrogen Clearance Blood Flow Sensor

PubMed Central

Walton, Lindsay R.; Edwards, Martin A.; McCarty, Gregory S.; Wightman, R. Mark

2016-01-01

Background Modern cerebral blood flow (CBF) detection favors the use of either optical technologies that are limited to cortical brain regions, or expensive magnetic resonance. Decades ago, inhalation gas clearance was the choice method of quantifying CBF, but this suffered from poor temporal resolution. Electrolytic H2 clearance (EHC) generates and collects gas in situ at an electrode pair, which improves temporal resolution, but the probe size has prohibited meaningful subcortical use. New Method We microfabricated EHC electrodes to an order of magnitude smaller than those existing, on the scale of 100 µm, to permit use deep within the brain. Results Novel EHC probes were fabricated. The devices offered exceptional signal-to-noise, achieved high collection efficiencies (40 – 50%) in vitro, and agreed with theoretical modeling. An in vitro chemical reaction model was used to confirm that our devices detected flow rates higher than those expected physiologically. Computational modeling that incorporated realistic noise levels demonstrated devices would be sensitive to physiological CBF rates. Comparison with Existing Method The reduced size of our arrays makes them suitable for subcortical EHC measurements, as opposed to the larger, existing EHC electrodes that would cause substantial tissue damage. Our array can collect multiple CBF measurements per minute, and can thus resolve physiological changes occurring on a shorter timescale than existing gas clearance measurements. Conclusion We present and characterize microfabricated EHC electrodes and an accompanying theoretical model to interpret acquired data. Microfabrication allows for the high-throughput production of reproducible devices that are capable of monitoring deep brain CBF with sub-minute resolution. PMID:27102042

Simulating effects of brain atrophy in longitudinal PET imaging with an anthropomorphic brain phantom

NASA Astrophysics Data System (ADS)

Jonasson, L. S.; Axelsson, J.; Riklund, K.; Boraxbekk, C. J.

2017-07-01

In longitudinal positron emission tomography (PET), the presence of volumetric changes over time can lead to an overestimation or underestimation of the true changes in the quantified PET signal due to the partial volume effect (PVE) introduced by the limited spatial resolution of existing PET cameras and reconstruction algorithms. Here, a 3D-printed anthropomorphic brain phantom with attachable striata in three sizes was designed to enable controlled volumetric changes. Using a method to eliminate the non-radioactive plastic wall, and manipulating BP levels by adding different number of events from list-mode acquisitions, we investigated the artificial volume dependence of BP due to PVE, and potential bias arising from varying BP. Comparing multiple reconstruction algorithms we found that a high-resolution ordered-subsets maximization algorithm with spatially variant point-spread function resolution modeling provided the most accurate data. For striatum, the BP changed by 0.08% for every 1% volume change, but for smaller volumes such as the posterior caudate the artificial change in BP was as high as 0.7% per 1% volume change. A simple gross correction for striatal volume is unsatisfactory, as the amplitude of the PVE on the BP differs depending on where in the striatum the change occurred. Therefore, to correctly interpret age-related longitudinal changes in the BP, we must account for volumetric changes also within a structure, rather than across the whole volume. The present 3D-printing technology, combined with the wall removal method, can be implemented to gain knowledge about the predictable bias introduced by the PVE differences in uptake regions of varying shape.

Positron Emission Tomography (PET) and Positron Scanning

Science.gov Websites

National Laboratory 'Positron Emission Tomography ... [is a medical imaging technique that] can track human brain.' Edited excerpts from from Medical Applications of Non-Medical Research: Applications Technical Report, November 1988 High-resolution PET (Positron Emission Tomography) for Medical Science

A 3D MRI-based atlas of a lizard brain.

PubMed

Hoops, Daniel; Desfilis, Ester; Ullmann, Jeremy F P; Janke, Andrew L; Stait-Gardner, Timothy; Devenyi, Gabriel A; Price, William S; Medina, Loreta; Whiting, Martin J; Keogh, J Scott

2018-06-22

Magnetic resonance imaging (MRI) is an established technique for neuroanatomical analysis, being particularly useful in the medical sciences. However, the application of MRI to evolutionary neuroscience is still in its infancy. Few magnetic resonance brain atlases exist outside the standard model organisms in neuroscience and no magnetic resonance atlas has been produced for any reptile brain. A detailed understanding of reptilian brain anatomy is necessary to elucidate the evolutionary origin of enigmatic brain structures such as the cerebral cortex. Here, we present a magnetic resonance atlas for the brain of a representative squamate reptile, the Australian tawny dragon (Agamidae: Ctenophorus decresii), which has been the object of numerous ecological and behavioral studies. We used a high-field 11.74T magnet, a paramagnetic contrasting-enhancing agent and minimum-deformation modeling of the brains of thirteen adult male individuals. From this, we created a high-resolution three-dimensional model of a lizard brain . The 3D-MRI model can be freely downloaded and allows a better comprehension of brain areas, nuclei, and fiber tracts, facilitating comparison with other species and setting the basis for future comparative evolution imaging studies. The MRI model of a tawny dragon brain (Ctenophorus decresii) can be viewed online and downloaded using the Wiley Biolucida Server at wiley.biolucida.net. This article is protected by copyright. All rights reserved. © 2018 Wiley Periodicals, Inc.

Evaluation of five diffeomorphic image registration algorithms for mouse brain magnetic resonance microscopy.

PubMed

Fu, Zhenrong; Lin, Lan; Tian, Miao; Wang, Jingxuan; Zhang, Baiwen; Chu, Pingping; Li, Shaowu; Pathan, Muhammad Mohsin; Deng, Yulin; Wu, Shuicai

2017-11-01

The development of genetically engineered mouse models for neuronal diseases and behavioural disorders have generated a growing need for small animal imaging. High-resolution magnetic resonance microscopy (MRM) provides powerful capabilities for noninvasive studies of mouse brains, while avoiding some limits associated with the histological procedures. Quantitative comparison of structural images is a critical step in brain imaging analysis, which highly relies on the performance of image registration techniques. Nowadays, there is a mushrooming growth of human brain registration algorithms, while fine-tuning of those algorithms for mouse brain MRMs is rarely addressed. Because of their topology preservation property and outstanding performance in human studies, diffeomorphic transformations have become popular in computational anatomy. In this study, we specially tuned five diffeomorphic image registration algorithms [DARTEL, geodesic shooting, diffeo-demons, SyN (Greedy-SyN and geodesic-SyN)] for mouse brain MRMs and evaluated their performance using three measures [volume overlap percentage (VOP), residual intensity error (RIE) and surface concordance ratio (SCR)]. Geodesic-SyN performed significantly better than the other methods according to all three different measures. These findings are important for the studies on structural brain changes that may occur in wild-type and transgenic mouse brains. © 2017 The Authors Journal of Microscopy © 2017 Royal Microscopical Society.

Brain Volume Estimation Enhancement by Morphological Image Processing Tools.

PubMed

Zeinali, R; Keshtkar, A; Zamani, A; Gharehaghaji, N

2017-12-01

Volume estimation of brain is important for many neurological applications. It is necessary in measuring brain growth and changes in brain in normal/abnormal patients. Thus, accurate brain volume measurement is very important. Magnetic resonance imaging (MRI) is the method of choice for volume quantification due to excellent levels of image resolution and between-tissue contrast. Stereology method is a good method for estimating volume but it requires to segment enough MRI slices and have a good resolution. In this study, it is desired to enhance stereology method for volume estimation of brain using less MRI slices with less resolution. In this study, a program for calculating volume using stereology method has been introduced. After morphologic method, dilation was applied and the stereology method enhanced. For the evaluation of this method, we used T1-wighted MR images from digital phantom in BrainWeb which had ground truth. The volume of 20 normal brain extracted from BrainWeb, was calculated. The volumes of white matter, gray matter and cerebrospinal fluid with given dimension were estimated correctly. Volume calculation from Stereology method in different cases was made. In three cases, Root Mean Square Error (RMSE) was measured. Case I with T=5, d=5, Case II with T=10, D=10 and Case III with T=20, d=20 (T=slice thickness, d=resolution as stereology parameters). By comparing these results of two methods, it is obvious that RMSE values for our proposed method are smaller than Stereology method. Using morphological operation, dilation allows to enhance the estimation volume method, Stereology. In the case with less MRI slices and less test points, this method works much better compared to Stereology method.

TandemPET-A High Resolution, Small Animal, Virtual Pinhole-Based PET Scanner: Initial Design Study

NASA Astrophysics Data System (ADS)

Raylman, Raymond R.; Stolin, Alexander V.; Martone, Peter F.; Smith, Mark F.

2016-02-01

Mice are the perhaps the most common species of rodents used in biomedical research, but many of the current generation of small animal PET scanners are non-optimal for imaging these small rodents due to their relatively low resolution. Consequently, a number of researchers have investigated the development of high-resolution scanners to address this need. In this investigation, the design of a novel, high-resolution system based on the dual-detector, virtual-pinhole PET concept was explored via Monte Carlo simulations. Specifically, this system, called TandemPET, consists of a 5 cm × 5 cm high-resolution detector made-up of a 90 × 90 array of 0.5 mm × 0.5 × 10 mm (pitch = 0.55 mm) LYSO detector elements in coincidence with a lower resolution detector consisting of a 68 × 68 array of 1.5 mm × 1.5 mm × 10 mm LYSO detector elements (total size = 10.5 cm × 10.5 cm). Analyses indicated that TandemPET's optimal geometry is to position the high-resolution detector 3 cm from the center-of-rotation, with the lower resolution detector positioned 9 cm from center. Measurements using modified NEMA NU4-2008-based protocols revealed that the spatial resolution of the system is 0.5 mm FWHM, after correction of positron range effects. Peak sensitivity is 2.1%, which is comparable to current small animal PET scanners. Images from a digital mouse brain phantom demonstrated the potential of the system for identifying important neurological structures.

Diffusion weighted imaging: a comprehensive evaluation of a fast spin echo DWI sequence with BLADE (PROPELLER) k-space sampling at 3 T, using a 32-channel head coil in acute brain ischemia.

PubMed

Attenberger, Ulrike I; Runge, Val M; Stemmer, Alto; Williams, Kenneth D; Naul, L Gill; Michaely, Henrik J; Schoenberg, Stefan O; Reiser, Maximilian F; Wintersperger, Bernd J

2009-10-01

To evaluate the signal-to-noise ratio (SNR) and diagnostic quality of diffusion weighted imaging (DWI) using a fast spin echo (FSE) sequence with BLADE k-space trajectory at 3 T in combination with a 32-channel head coil. The scan was compared with a standard spin echo (SE) echo-planar imaging (EPI) DWI and a high resolution SE EPI DWI sequence. Fourteen patients with acute brain ischemia were included in this Institutional Review Board approved study. All patients were evaluated with 3 different image sequences, using a 3 T scanner and a 32-channel head coil: (a) a standard SE EPI DWI (matrix size 192 x 192), (b) a high resolution SE EPI DWI (matrix size of 256 x 256) and (c) a FSE DWI BLADE (matrix size 192 x 192). The SNR of the 3 scans was compared in 10 healthy volunteers by a paired student t test. Image quality was evaluated with 4 dedicated questions in a blinded read: (1) The scans were ranked in terms of bulk susceptibility artifact. (2) The scan preference for diagnosis of any diffusion abnormality that might occur and (3) the preference for visualization of the diffusion abnormality actually present was determined. (4) The influence of bulk susceptibility on image evaluation for the diffusion abnormality present was assessed. For visualization of the diffusion abnormality present, BLADE DWI was the scan sequence preferred most by both readers (reader 1: 41.7%, reader 2: 35.7%). For visualization of any diffusion abnormality present, BLADE DWI was the preferred scan in 13 of 14 cases for reader 1 (93%) and in 11 of 14 cases for reader 2 (78.6%). No high resolution SE EPI DWI scan was rated best by reader 1. Reader 2 rated the high resolution SE EPI DWI scan superior in only 1 of 56 judgments. The standard EPI DWI sequence (21.8 +/- 5.3) had in comparison to the high resolution EPI DWI (11.9 +/- 2.6) and the BLADE DWI scans (11.3 +/- 3.8) significantly higher SNR mean values. Our preliminary data demonstrates the feasibility of a FSE EPI DWI scan with radial-like k-space sampling, using a 32-channel coil at 3 T in acute brain ischemia. The BLADE DWI was the preferred scan for the detection of acute diffusion abnormalities because of the lack of bulk susceptibility artifacts.

Deep brain two-photon NIR fluorescence imaging for study of Alzheimer's disease

NASA Astrophysics Data System (ADS)

Chen, Congping; Liang, Zhuoyi; Zhou, Biao; Ip, Nancy Y.; Qu, Jianan Y.

2018-02-01

Amyloid depositions in the brain represent the characteristic hallmarks of Alzheimer's disease (AD) pathology. The abnormal accumulation of extracellular amyloid-beta (Aβ) and resulting toxic amyloid plaques are considered to be responsible for the clinical deficits including cognitive decline and memory loss. In vivo two-photon fluorescence imaging of amyloid plaques in live AD mouse model through a chronic imaging window (thinned skull or craniotomy) provides a mean to greatly facilitate the study of the pathological mechanism of AD owing to its high spatial resolution and long-term continuous monitoring. However, the imaging depth for amyloid plaques is largely limited to upper cortical layers due to the short-wavelength fluorescence emission of commonly used amyloid probes. In this work, we reported that CRANAD-3, a near-infrared (NIR) probe for amyloid species with excitation wavelength at 900 nm and emission wavelength around 650 nm, has great advantages over conventionally used probes and is well suited for twophoton deep imaging of amyloid plaques in AD mouse brain. Compared with a commonly used MeO-X04 probe, the imaging depth of CRANAD-3 is largely extended for open skull cranial window. Furthermore, by using two-photon excited fluorescence spectroscopic imaging, we characterized the intrinsic fluorescence of the "aging pigment" lipofuscin in vivo, which has distinct spectra from CRANAD-3 labeled plaques. This study reveals the unique potential of NIR probes for in vivo, high-resolution and deep imaging of brain amyloid in Alzheimer's disease.

Nanotomography of brain networks

NASA Astrophysics Data System (ADS)

Saiga, Rino; Mizutani, Ryuta; Takekoshi, Susumu; Osawa, Motoki; Arai, Makoto; Takeuchi, Akihisa; Uesugi, Kentaro; Terada, Yasuko; Suzuki, Yoshio; de Andrade, Vincent; de Carlo, Francesco

The first step to understanding how the brain functions is to analyze its 3D network. The brain network consists of neurons having micrometer to nanometer sized structures. Therefore, 3D analysis of brain tissue at the relevant resolution is essential for elucidating brain's functional mechanisms. Here, we report 3D structures of human and fly brain networks revealed with synchrotron radiation nanotomography, or nano-CT. Neurons were stained with high-Z elements to visualize their structures with X-rays. Nano-CT experiments were then performed at the 32-ID beamline of the Advanced Photon Source, Argonne National Laboratory and at the BL37XU and BL47XU beamlines of SPring-8. Reconstructed 3D images illustrated precise structures of human neurons, including dendritic spines responsible for synaptic connections. The network of the fly brain hemisphere was traced to build a skeletonized wire model. An article reviewing our study appeared in MIT Technology Review. Movies of the obtained structures can be found in our YouTube channel.

Reconstruction of human brain spontaneous activity based on frequency-pattern analysis of magnetoencephalography data

PubMed Central

Llinás, Rodolfo R.; Ustinin, Mikhail N.; Rykunov, Stanislav D.; Boyko, Anna I.; Sychev, Vyacheslav V.; Walton, Kerry D.; Rabello, Guilherme M.; Garcia, John

2015-01-01

A new method for the analysis and localization of brain activity has been developed, based on multichannel magnetic field recordings, over minutes, superimposed on the MRI of the individual. Here, a high resolution Fourier Transform is obtained over the entire recording period, leading to a detailed multi-frequency spectrum. Further analysis implements a total decomposition of the frequency components into functionally invariant entities, each having an invariant field pattern localizable in recording space. The method, addressed as functional tomography, makes it possible to find the distribution of magnetic field sources in space. Here, the method is applied to the analysis of simulated data, to oscillating signals activating a physical current dipoles phantom, and to recordings of spontaneous brain activity in 10 healthy adults. In the analysis of simulated data, 61 dipoles are localized with 0.7 mm precision. Concerning the physical phantom the method is able to localize three simultaneously activated current dipoles with 1 mm precision. Spatial resolution 3 mm was attained when localizing spontaneous alpha rhythm activity in 10 healthy adults, where the alpha peak was specified for each subject individually. Co-registration of the functional tomograms with each subject's head MRI localized alpha range activity to the occipital and/or posterior parietal brain region. This is the first application of this new functional tomography to human brain activity. The method successfully provides an overall view of brain electrical activity, a detailed spectral description and, combined with MRI, the localization of sources in anatomical brain space. PMID:26528119

Multi-modal imaging of long-term recovery post-stroke by positron emission tomography and matrix-assisted laser desorption/ionisation mass spectrometry.

PubMed

Henderson, Fiona; Hart, Philippa J; Pradillo, Jesus M; Kassiou, Michael; Christie, Lidan; Williams, Kaye J; Boutin, Herve; McMahon, Adam

2018-05-15

Stroke is a leading cause of disability worldwide. Understanding the recovery process post-stroke is essential; however, longer-term recovery studies are lacking. In vivo positron emission tomography (PET) can image biological recovery processes, but is limited by spatial resolution and its targeted nature. Untargeted mass spectrometry imaging offers high spatial resolution, providing an ideal ex vivo tool for brain recovery imaging. Magnetic resonance imaging (MRI) was used to image a rat brain 48 h after ischaemic stroke to locate the infarcted regions of the brain. PET was carried out 3 months post-stroke using the tracers [ 18 F]DPA-714 for TSPO and [ 18 F]IAM6067 for sigma-1 receptors to image neuroinflammation and neurodegeneration, respectively. The rat brain was flash-frozen immediately after PET scanning, and sectioned for matrix-assisted laser desorption/ionisation mass spectrometry (MALDI-MS) imaging. Three months post-stroke, PET imaging shows minimal detection of neurodegeneration and neuroinflammation, indicating that the brain has stabilised. However, MALDI-MS images reveal distinct differences in lipid distributions (e.g. phosphatidylcholine and sphingomyelin) between the scar and the healthy brain, suggesting that recovery processes are still in play. It is currently not known if the altered lipids in the scar will change on a longer time scale, or if they are stabilised products of the brain post-stroke. The data demonstrates the ability to combine MALD-MS with in vivo PET to image different aspects of stroke recovery. Copyright © 2018 John Wiley & Sons, Ltd.

The diffusion tensor imaging (DTI) component of the NIH MRI study of normal brain development (PedsDTI).

PubMed

Walker, Lindsay; Chang, Lin-Ching; Nayak, Amritha; Irfanoglu, M Okan; Botteron, Kelly N; McCracken, James; McKinstry, Robert C; Rivkin, Michael J; Wang, Dah-Jyuu; Rumsey, Judith; Pierpaoli, Carlo

2016-01-01

The NIH MRI Study of normal brain development sought to characterize typical brain development in a population of infants, toddlers, children and adolescents/young adults, covering the socio-economic and ethnic diversity of the population of the United States. The study began in 1999 with data collection commencing in 2001 and concluding in 2007. The study was designed with the final goal of providing a controlled-access database; open to qualified researchers and clinicians, which could serve as a powerful tool for elucidating typical brain development and identifying deviations associated with brain-based disorders and diseases, and as a resource for developing computational methods and image processing tools. This paper focuses on the DTI component of the NIH MRI study of normal brain development. In this work, we describe the DTI data acquisition protocols, data processing steps, quality assessment procedures, and data included in the database, along with database access requirements. For more details, visit http://www.pediatricmri.nih.gov. This longitudinal DTI dataset includes raw and processed diffusion data from 498 low resolution (3 mm) DTI datasets from 274 unique subjects, and 193 high resolution (2.5 mm) DTI datasets from 152 unique subjects. Subjects range in age from 10 days (from date of birth) through 22 years. Additionally, a set of age-specific DTI templates are included. This forms one component of the larger NIH MRI study of normal brain development which also includes T1-, T2-, proton density-weighted, and proton magnetic resonance spectroscopy (MRS) imaging data, and demographic, clinical and behavioral data. Published by Elsevier Inc.

Hybrid ultrasound and dual-wavelength optoacoustic biomicroscopy for functional neuroimaging

NASA Astrophysics Data System (ADS)

Rebling, Johannes; Estrada, Hector; Zwack, Michael; Sela, Gali; Gottschalk, Sven; Razansky, Daniel

2017-03-01

Many neurological disorders are linked to abnormal activation or pathological alterations of the vasculature in the affected brain region. Obtaining simultaneous morphological and physiological information of neurovasculature is very challenging due to the acoustic distortions and intense light scattering by the skull and brain. In addition, the size of cerebral vasculature in murine brains spans an extended range from just a few microns up to about a millimeter, all to be recorded in 3D and over an area of several dozens of mm2. Numerous imaging techniques exist that excel at characterizing certain aspects of this complex network but are only capable of providing information on a limited spatiotemporal scale. We present a hybrid ultrasound and dual-wavelength optoacoustic microscope, capable of rapid imaging of murine neurovasculature in-vivo, with high spatial resolution down to 12 μm over a large field of view exceeding 50mm2. The dual wavelength imaging capability allows for the visualization of functional blood parameters through an intact skull while pulse-echo ultrasound biomicroscopy images are captured simultaneously by the same scan head. The flexible hybrid design in combination with fast high-resolution imaging in 3D holds promise for generating better insights into the architecture and function of the neurovascular system.

High efficiency multishot interleaved spiral-in/out: acquisition for high-resolution BOLD fMRI.

PubMed

Jung, Youngkyoo; Samsonov, Alexey A; Liu, Thomas T; Buracas, Giedrius T

2013-08-01

Growing demand for high spatial resolution blood oxygenation level dependent (BOLD) functional magnetic resonance imaging faces a challenge of the spatial resolution versus coverage or temporal resolution tradeoff, which can be addressed by methods that afford increased acquisition efficiency. Spiral acquisition trajectories have been shown to be superior to currently prevalent echo-planar imaging in terms of acquisition efficiency, and high spatial resolution can be achieved by employing multiple-shot spiral acquisition. The interleaved spiral in/out trajectory is preferred over spiral-in due to increased BOLD signal contrast-to-noise ratio (CNR) and higher acquisition efficiency than that of spiral-out or noninterleaved spiral in/out trajectories (Law & Glover. Magn Reson Med 2009; 62:829-834.), but to date applicability of the multishot interleaved spiral in/out for high spatial resolution imaging has not been studied. Herein we propose multishot interleaved spiral in/out acquisition and investigate its applicability for high spatial resolution BOLD functional magnetic resonance imaging. Images reconstructed from interleaved spiral-in and -out trajectories possess artifacts caused by differences in T2 decay, off-resonance, and k-space errors associated with the two trajectories. We analyze the associated errors and demonstrate that application of conjugate phase reconstruction and spectral filtering can substantially mitigate these image artifacts. After applying these processing steps, the multishot interleaved spiral in/out pulse sequence yields high BOLD CNR images at in-plane resolution below 1 × 1 mm while preserving acceptable temporal resolution (4 s) and brain coverage (15 slices of 2 mm thickness). Moreover, this method yields sufficient BOLD CNR at 1.5 mm isotropic resolution for detection of activation in hippocampus associated with cognitive tasks (Stern memory task). The multishot interleaved spiral in/out acquisition is a promising technique for high spatial resolution BOLD functional magnetic resonance imaging applications. © 2012 Wiley Periodicals, Inc.

Design and evaluation of two multi-pinhole collimators for brain SPECT.

PubMed

Chen, Ling; Tsui, Benjamin M W; Mok, Greta S P

2017-10-01

SPECT is a powerful tool for diagnosing or staging brain diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD) but is limited by its inferior resolution and sensitivity. At the same time, pinhole SPECT provides superior resolution and detection efficiency trade-off as compared to the conventional parallel-hole collimator for imaging small field-of-view (FOV), which fits for the case of brain imaging. In this study, we propose to develop and evaluate two multi-pinhole (MPH) collimator designs to improve the imaging of cerebral blood flow and striatum. We set the target resolutions to be 12 and 8 mm, respectively, and the FOV at 200 mm which is large enough to cover the whole brain. The constraints for system optimization include maximum and minimum detector-to-center-of-FOV (CFOV) distances of 344 and 294 mm, respectively, and minimal radius-of-rotation (ROR) of 135 mm to accommodate patients' shoulder. According to the targeted FOV, resolutions, and constraints, we determined the pinhole number, ROR, focal length, aperture acceptance angle, and aperture diameter which maximized the system sensitivity. We then assessed the imaging performance of the proposed MPH and standard low-energy high-resolution (LEHR) collimators using analytical simulations of a digital NCAT brain phantom with 99m Tc-HMPAO/ 99m Tc-TRODAT-1 distributions; Monte Carlo simulations of a hot-rod phantom; and a Defrise phantom using GATE v6.1. Projections were generated over 360° and reconstructed using the 3D MPH/LEHR OS-EM methods with up to 720 updates. The normalized mean square error (NMSE) was calculated over the cerebral and striatal regions extracted from the reconstructed images for 99m Tc-HMPAO and 99m Tc-TRODAT-1 simulations, respectively, and average normalized standard deviation (NSD) based on 20 noise realizations was assessed on selected uniform 3D regions as the noise index. Visual assessment and image profiles were applied to the results of Monte Carlo simulations. The optimized design parameters of the MPH collimators were 9 pinholes with 4.7 and 2.8 mm pinhole diameter, 73° acceptance angle, 127 mm focal length, 167 mm ROR for 12 mm and 8 mm target resolution, respectively. According to the optimization results, the detection efficiencies of the proposed collimators were 270 and 40% more as compared to LEHR. The Monte Carlo simulations showed that 7.9 and 6.4 mm rods can be discriminated for the MPH collimators with target resolutions of 12 and 8 mm, respectively. The eight 12 mm-thick discs of the Defrise phantom can also be resolved clearly in the axial plane as demonstrated by the image profiles generated with the MPH collimators. The two collimator designs provide superior image quality as compared to the conventional LEHR, and shows potential to improve current brain SPECT imaging based on a conventional SPECT scanner.

Functional brain microstate predicts the outcome in a visuospatial working memory task.

PubMed

Muthukrishnan, Suriya-Prakash; Ahuja, Navdeep; Mehta, Nalin; Sharma, Ratna

2016-11-01

Humans have limited capacity of processing just up to 4 integrated items of information in the working memory. Thus, it is inevitable to commit more errors when challenged with high memory loads. However, the neural mechanisms that determine the accuracy of response at high memory loads still remain unclear. High temporal resolution of Electroencephalography (EEG) technique makes it the best tool to resolve the temporal dynamics of brain networks. EEG-defined microstate is the quasi-stable scalp electrical potential topography that represents the momentary functional state of brain. Thus, it has been possible to assess the information processing currently performed by the brain using EEG microstate analysis. We hypothesize that the EEG microstate preceding the trial could determine its outcome in a visuospatial working memory (VSWM) task. Twenty-four healthy participants performed a high memory load VSWM task, while their brain activity was recorded using EEG. Four microstate maps were found to represent the functional brain state prior to the trials in the VSWM task. One pre-trial microstate map was found to determine the accuracy of subsequent behavioural response. The intracranial generators of the pre-trial microstate map that determined the response accuracy were localized to the visuospatial processing areas at bilateral occipital, right temporal and limbic cortices. Our results imply that the behavioural outcome in a VSWM task could be determined by the intensity of activation of memory representations in the visuospatial processing brain regions prior to the trial. Copyright © 2016 Elsevier B.V. All rights reserved.

Performance of a high-resolution depth-encoding PET detector module using linearly-graded SiPM arrays

NASA Astrophysics Data System (ADS)

Du, Junwei; Bai, Xiaowei; Gola, Alberto; Acerbi, Fabio; Ferri, Alessandro; Piemonte, Claudio; Yang, Yongfeng; Cherry, Simon R.

2018-02-01

The goal of this study was to exploit the excellent spatial resolution characteristics of a position-sensitive silicon photomultiplier (SiPM) and develop a high-resolution depth-of-interaction (DOI) encoding positron emission tomography (PET) detector module. The detector consists of a 30  ×  30 array of 0.445  ×  0.445  ×  20 mm3 polished LYSO crystals coupled to two 15.5  ×  15.5 mm2 linearly-graded SiPM (LG-SiPM) arrays at both ends. The flood histograms show that all the crystals in the LYSO array can be resolved. The energy resolution, the coincidence timing resolution and the DOI resolution were 21.8  ±  5.8%, 1.23  ±  0.10 ns and 3.8  ±  1.2 mm, respectively, at a temperature of -10 °C and a bias voltage of 35.0 V. The performance did not degrade significantly for event rates of up to 130 000 counts s-1. This detector represents an attractive option for small-bore PET scanner designs that simultaneously emphasize high spatial resolution and high detection efficiency, important, for example, in preclinical imaging of the rodent brain with neuroreceptor ligands.

Demeclocycline as a contrast agent for detecting brain neoplasms using confocal microscopy

NASA Astrophysics Data System (ADS)

Wirth, Dennis; Smith, Thomas W.; Moser, Richard; Yaroslavsky, Anna N.

2015-04-01

Complete resection of brain tumors improves life expectancy and quality. Thus, there is a strong need for high-resolution detection and microscopically controlled removal of brain neoplasms. The goal of this study was to test demeclocycline as a contrast enhancer for the intraoperative detection of brain tumors. We have imaged benign and cancerous brain tumors using multimodal confocal microscopy. The tumors investigated included pituitary adenoma, meningiomas, glioblastomas, and metastatic brain cancers. Freshly excised brain tissues were stained in 0.75 mg ml-1 aqueous solution of demeclocyline. Reflectance images were acquired at 402 nm. Fluorescence signals were excited at 402 nm and registered between 500 and 540 nm. After imaging, histological sections were processed from the imaged specimens and compared to the optical images. Fluorescence images highlighted normal and cancerous brain cells, while reflectance images emphasized the morphology of connective tissue. The optical and histological images were in accordance with each other for all types of tumors investigated. Demeclocyline shows promise as a contrast agent for intraoperative detection of brain tumors.

Primate Brain Anatomy: New Volumetric MRI Measurements for Neuroanatomical Studies.

PubMed

Navarrete, Ana F; Blezer, Erwin L A; Pagnotta, Murillo; de Viet, Elizabeth S M; Todorov, Orlin S; Lindenfors, Patrik; Laland, Kevin N; Reader, Simon M

2018-06-12

Since the publication of the primate brain volumetric dataset of Stephan and colleagues in the early 1980s, no major new comparative datasets covering multiple brain regions and a large number of primate species have become available. However, technological and other advances in the last two decades, particularly magnetic resonance imaging (MRI) and the creation of institutions devoted to the collection and preservation of rare brain specimens, provide opportunities to rectify this situation. Here, we present a new dataset including brain region volumetric measurements of 39 species, including 20 species not previously available in the literature, with measurements of 16 brain areas. These volumes were extracted from MRI of 46 brains of 38 species from the Netherlands Institute of Neuroscience Primate Brain Bank, scanned at high resolution with a 9.4-T scanner, plus a further 7 donated MRI of 4 primate species. Partial measurements were made on an additional 8 brains of 5 species. We make the dataset and MRI scans available online in the hope that they will be of value to researchers conducting comparative studies of primate evolution. © 2018 S. Karger AG, Basel.

Quantitative comparison of high-resolution MRI and myelin-stained histology of the human cerebral cortex.

PubMed

Osechinskiy, Sergey; Kruggel, Frithjof

2009-01-01

The architectonic analysis of the human cerebral cortex is presently based on the examination of stained tissue sections. Recent progress in high-resolution magnetic resonance imaging (MRI) promotes the feasibility of an in vivo architectonic analysis. Since the exact relationship between the laminar fine-structure of a cortical MRI signal and histological cyto-and myeloarchitectonic staining patterns is not known, a quantitative study comparing high-resolution MRI to histological ground truth images is necessary for validating a future MRI based architectonic analysis. This communication describes an ongoing study comparing post mortem MR images to a myelin-stained histology of the brain cortex. After establishing a close spatial correspondence between histological sections and MRI using a slice-to-volume nonrigid registration algorithm, transcortical intensity profiles, extracted from both imaging modalities along curved trajectories of a Laplacian vector field, are compared via a cross-correlational analysis.

Magnetic eye tracking in mice

PubMed Central

Payne, Hannah L

2017-01-01

Eye movements provide insights about a wide range of brain functions, from sensorimotor integration to cognition; hence, the measurement of eye movements is an important tool in neuroscience research. We describe a method, based on magnetic sensing, for measuring eye movements in head-fixed and freely moving mice. A small magnet was surgically implanted on the eye, and changes in the magnet angle as the eye rotated were detected by a magnetic field sensor. Systematic testing demonstrated high resolution measurements of eye position of <0.1°. Magnetic eye tracking offers several advantages over the well-established eye coil and video-oculography methods. Most notably, it provides the first method for reliable, high-resolution measurement of eye movements in freely moving mice, revealing increased eye movements and altered binocular coordination compared to head-fixed mice. Overall, magnetic eye tracking provides a lightweight, inexpensive, easily implemented, and high-resolution method suitable for a wide range of applications. PMID:28872455

Matrix Sublimation/Recrystallization for Imaging Proteins by Mass Spectrometry at High Spatial Resolution

PubMed Central

Yang, Junhai; Caprioli, Richard M.

2011-01-01

We have employed matrix deposition by sublimation for protein image analysis on tissue sections using a hydration/recrystallization process that produces high quality MALDI mass spectra and high spatial resolution ion images. We systematically investigated different washing protocols, the effect of tissue section thickness, the amount of sublimated matrix per unit area and different recrystallization conditions. The results show that an organic solvent rinse followed by ethanol/water rinses substantially increased sensitivity for the detection of proteins. Both the thickness of tissue section and amount of sinapinic acid sublimated per unit area have optimal ranges for maximal protein signal intensity. Ion images of mouse and rat brain sections at 50, 20 and 10 µm spatial resolution are presented and are correlated with H&E stained optical images. For targeted analysis, histology directed imaging can be performed using this protocol where MS analysis and H&E staining are performed on the same section. PMID:21639088

White matter segmentation by estimating tissue optical attenuation from volumetric OCT massive histology of whole rodent brains

NASA Astrophysics Data System (ADS)

Lefebvre, Joël.; Castonguay, Alexandre; Lesage, Frédéric

2017-02-01

A whole rodent brain was imaged using an automated massive histology setup and an Optical Coherence Tomography (OCT) microscope. Thousands of OCT volumetric tiles were acquired, each covering a size of about 2.5x2.5x0.8 mm3 with a sampling resolution of 4.9x4.9x6.5 microns. This paper shows the techniques for reconstruction, attenuation compensation and segmentation of the sliced brains. The tile positions within the mosaic were evaluated using a displacement model of the motorized stage and pairwise coregistration. Volume blending was then performed by solving the 3D Laplace equation, and consecutive slices were assembled using the cross-correlation of their 2D image gradient. This reconstruction algorithm resulted in a 3D map of optical reflectivity for the whole brain at micrometric resolution. OCT tissue slices were then used to estimate the local attenuation coefficient based on a single scattering photon model. The attenuation map obtained exhibits a high contrast for all white matter fibres, regardless of their orientation. The tissue optical attenuation from the intrinsic OCT reflectivity contributes to better white matter tissue segmentation. The combined 3D maps of reflectivity and attenuation is a step toward the study of white matter at a microscopic scale for the whole brain in small animals.

Intensity standardisation of 7T MR images for intensity-based segmentation of the human hypothalamus

PubMed Central

Schreiber, Jan; Bazin, Pierre-Louis; Trampel, Robert; Anwander, Alfred; Geyer, Stefan; Schönknecht, Peter

2017-01-01

The high spatial resolution of 7T MRI enables us to identify subtle volume changes in brain structures, providing potential biomarkers of mental disorders. Most volumetric approaches require that similar intensity values represent similar tissue types across different persons. By applying colour-coding to T1-weighted MP2RAGE images, we found that the high measurement accuracy achieved by high-resolution imaging may be compromised by inter-individual variations in the image intensity. To address this issue, we analysed the performance of five intensity standardisation techniques in high-resolution T1-weighted MP2RAGE images. Twenty images with extreme intensities in the GM and WM were standardised to a representative reference image. We performed a multi-level evaluation with a focus on the hypothalamic region—analysing the intensity histograms as well as the actual MR images, and requiring that the correlation between the whole-brain tissue volumes and subject age be preserved during standardisation. The results were compared with T1 maps. Linear standardisation using subcortical ROIs of GM and WM provided good results for all evaluation criteria: it improved the histogram alignment within the ROIs and the average image intensity within the ROIs and the whole-brain GM and WM areas. This method reduced the inter-individual intensity variation of the hypothalamic boundary by more than half, outperforming all other methods, and kept the original correlation between the GM volume and subject age intact. Mixed results were obtained for the other four methods, which sometimes came at the expense of unwarranted changes in the age-related pattern of the GM volume. The mapping of the T1 relaxation time with the MP2RAGE sequence is advertised as being especially robust to bias field inhomogeneity. We found little evidence that substantiated the T1 map’s theoretical superiority over the T1-weighted images regarding the inter-individual image intensity homogeneity. PMID:28253330

Automated generation of massive image knowledge collections using Microsoft Live Labs Pivot to promote neuroimaging and translational research

PubMed Central

2011-01-01

Background Massive datasets comprising high-resolution images, generated in neuro-imaging studies and in clinical imaging research, are increasingly challenging our ability to analyze, share, and filter such images in clinical and basic translational research. Pivot collection exploratory analysis provides each user the ability to fully interact with the massive amounts of visual data to fully facilitate sufficient sorting, flexibility and speed to fluidly access, explore or analyze the massive image data sets of high-resolution images and their associated meta information, such as neuro-imaging databases from the Allen Brain Atlas. It is used in clustering, filtering, data sharing and classifying of the visual data into various deep zoom levels and meta information categories to detect the underlying hidden pattern within the data set that has been used. Method We deployed prototype Pivot collections using the Linux CentOS running on the Apache web server. We also tested the prototype Pivot collections on other operating systems like Windows (the most common variants) and UNIX, etc. It is demonstrated that the approach yields very good results when compared with other approaches used by some researchers for generation, creation, and clustering of massive image collections such as the coronal and horizontal sections of the mouse brain from the Allen Brain Atlas. Results Pivot visual analytics was used to analyze a prototype of dataset Dab2 co-expressed genes from the Allen Brain Atlas. The metadata along with high-resolution images were automatically extracted using the Allen Brain Atlas API. It is then used to identify the hidden information based on the various categories and conditions applied by using options generated from automated collection. A metadata category like chromosome, as well as data for individual cases like sex, age, and plan attributes of a particular gene, is used to filter, sort and to determine if there exist other genes with a similar characteristics to Dab2. And online access to the mouse brain pivot collection can be viewed using the link http://edtech-dev.uthsc.edu/CTSI/teeDev1/unittest/PaPa/collection.html (user name: tviangte and password: demome) Conclusions Our proposed algorithm has automated the creation of large image Pivot collections; this will enable investigators of clinical research projects to easily and quickly analyse the image collections through a perspective that is useful for making critical decisions about the image patterns discovered. PMID:21884637

Volumetric multimodality neural network for brain tumor segmentation

NASA Astrophysics Data System (ADS)

Silvana Castillo, Laura; Alexandra Daza, Laura; Carlos Rivera, Luis; Arbeláez, Pablo

2017-11-01

Brain lesion segmentation is one of the hardest tasks to be solved in computer vision with an emphasis on the medical field. We present a convolutional neural network that produces a semantic segmentation of brain tumors, capable of processing volumetric data along with information from multiple MRI modalities at the same time. This results in the ability to learn from small training datasets and highly imbalanced data. Our method is based on DeepMedic, the state of the art in brain lesion segmentation. We develop a new architecture with more convolutional layers, organized in three parallel pathways with different input resolution, and additional fully connected layers. We tested our method over the 2015 BraTS Challenge dataset, reaching an average dice coefficient of 84%, while the standard DeepMedic implementation reached 74%.

Ultrasound imaging-guided intracardiac injection to develop a mouse model of breast cancer brain metastases followed by longitudinal MRI.

PubMed

Zhou, Heling; Zhao, Dawen

2014-03-06

Breast cancer brain metastasis, occurring in 30% of breast cancer patients at stage IV, is associated with high mortality. The median survival is only 6 months. It is critical to have suitable animal models to mimic the hemodynamic spread of the metastatic cells in the clinical scenario. Here, we are introducing the use of small animal ultrasound imaging to guide an accurate injection of brain tropical breast cancer cells into the left ventricle of athymic nude mice. Longitudinal MRI is used to assessing intracranial initiation and growth of brain metastases. Ultrasound-guided intracardiac injection ensures not only an accurate injection and hereby a higher successful rate but also significantly decreased mortality rate, as compared to our previous manual procedure. In vivo high resolution MRI allows the visualization of hyperintense multifocal lesions, as small as 310 µm in diameter on T2-weighted images at 3 weeks post injection. Follow-up MRI reveals intracranial tumor growth and increased number of metastases that distribute throughout the whole brain.

Optical-sectioning microscopy of protoporphyrin IX fluorescence in human gliomas: standardization and quantitative comparison with histology

NASA Astrophysics Data System (ADS)

Wei, Linpeng; Chen, Ye; Yin, Chengbo; Borwege, Sabine; Sanai, Nader; Liu, Jonathan T. C.

2017-04-01

Systemic delivery of 5-aminolevulinic acid leads to enhanced fluorescence image contrast in many tumors due to the increased accumulation of protoporphyrin IX (PpIX), a fluorescent porphyrin that is associated with tumor burden and proliferation. The value of PpIX-guided resection of malignant gliomas has been demonstrated in prospective randomized clinical studies in which a twofold greater extent of resection and improved progression-free survival have been observed. In low-grade gliomas and at the diffuse infiltrative margins of all gliomas, PpIX fluorescence is often too weak to be detected with current low-resolution surgical microscopes that are used in operating rooms. However, it has been demonstrated that high-resolution optical-sectioning microscopes are capable of detecting the sparse and punctate accumulations of PpIX that are undetectable via conventional low-power surgical fluorescence microscopes. To standardize the performance of high-resolution optical-sectioning devices for future clinical use, we have developed an imaging phantom and methods to ensure that the imaging of PpIX-expressing brain tissues can be performed reproducibly. Ex vivo imaging studies with a dual-axis confocal microscope demonstrate that these methods enable the acquisition of images from unsectioned human brain tissues that quantitatively and consistently correlate with images of histologically processed tissue sections.

High-resolution MRI of cranial nerves in posterior fossa at 3.0 T.

PubMed

Guo, Zi-Yi; Chen, Jing; Liang, Qi-Zhou; Liao, Hai-Yan; Cheng, Qiong-Yue; Fu, Shui-Xi; Chen, Cai-Xiang; Yu, Dan

2013-02-01

To evaluate the influence of high-resolution imaging obtainable with the higher field strength of 3.0 T on the visualization of the brain nerves in the posterior fossa. In total, 20 nerves were investigated on MRI of 12 volunteers each and selected for comparison, respectively, with the FSE sequences with 5 mm and 2 mm section thicknesses and gradient recalled echo (GRE) sequences acquired with a 3.0-T scanner. The MR images were evaluated by three independent readers who rated image quality according to depiction of anatomic detail and contrast with use of a rating scale. In general, decrease of the slice thickness showed a significant increase in the detection of nerves as well as in the image quality characteristics. Comparing FSE and GRE imaging, the course of brain nerves and brainstem vessels was visualized best with use of the three-dimensional (3D) pulse sequence. The comparison revealed the clear advantage of a thin section. The increased resolution enabled immediate identification of all brainstem nerves. GRE sequence most distinctly and confidently depicted pertinent structures and enables 3D reconstruction to illustrate complex relations of the brainstem. Copyright © 2013 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

Single-shot spiral imaging at 7 T.

PubMed

Engel, Maria; Kasper, Lars; Barmet, Christoph; Schmid, Thomas; Vionnet, Laetitia; Wilm, Bertram; Pruessmann, Klaas P

2018-03-25

The purpose of this work is to explore the feasibility and performance of single-shot spiral MRI at 7 T, using an expanded signal model for reconstruction. Gradient-echo brain imaging is performed on a 7 T system using high-resolution single-shot spiral readouts and half-shot spirals that perform dual-image acquisition after a single excitation. Image reconstruction is based on an expanded signal model including the encoding effects of coil sensitivity, static off-resonance, and magnetic field dynamics. The latter are recorded concurrently with image acquisition, using NMR field probes. The resulting image resolution is assessed by point spread function analysis. Single-shot spiral imaging is achieved at a nominal resolution of 0.8 mm, using spiral-out readouts of 53-ms duration. High depiction fidelity is achieved without conspicuous blurring or distortion. Effective resolutions are assessed as 0.8, 0.94, and 0.98 mm in CSF, gray matter and white matter, respectively. High image quality is also achieved with half-shot acquisition yielding image pairs at 1.5-mm resolution. Use of an expanded signal model enables single-shot spiral imaging at 7 T with unprecedented image quality. Single-shot and half-shot spiral readouts deploy the sensitivity benefit of high field for rapid high-resolution imaging, particularly for functional MRI and arterial spin labeling. © 2018 International Society for Magnetic Resonance in Medicine.

Implementation of a Gaussian Beam Laser and Aspheric Optics for High Spatial Resolution MALDI Imaging MS

NASA Astrophysics Data System (ADS)

Zavalin, Andre; Yang, Junhai; Haase, Andreas; Holle, Armin; Caprioli, Richard

2014-06-01

We have investigated the use of a Gaussian beam laser for MALDI Imaging Mass Spectrometry to provide a precisely defined laser spot of 5 μm diameter on target using a commercial MALDI TOF instrument originally designed to produce a 20 μm diameter laser beam spot at its smallest setting. A Gaussian beam laser was installed in the instrument in combination with an aspheric focusing lens. This ion source produced sharp ion images at 5 μm spatial resolution with signals of high intensity as shown for images from thin tissue sections of mouse brain.

Implementation of a Gaussian beam laser and aspheric optics for high spatial resolution MALDI imaging MS.

PubMed

Zavalin, Andre; Yang, Junhai; Haase, Andreas; Holle, Armin; Caprioli, Richard

2014-06-01

We have investigated the use of a Gaussian beam laser for MALDI Imaging Mass Spectrometry to provide a precisely defined laser spot of 5 μm diameter on target using a commercial MALDI TOF instrument originally designed to produce a 20 μm diameter laser beam spot at its smallest setting. A Gaussian beam laser was installed in the instrument in combination with an aspheric focusing lens. This ion source produced sharp ion images at 5 μm spatial resolution with signals of high intensity as shown for images from thin tissue sections of mouse brain.

Analysis strategies for high-resolution UHF-fMRI data.

PubMed

Polimeni, Jonathan R; Renvall, Ville; Zaretskaya, Natalia; Fischl, Bruce

2018-03-01

Functional MRI (fMRI) benefits from both increased sensitivity and specificity with increasing magnetic field strength, making it a key application for Ultra-High Field (UHF) MRI scanners. Most UHF-fMRI studies utilize the dramatic increases in sensitivity and specificity to acquire high-resolution data reaching sub-millimeter scales, which enable new classes of experiments to probe the functional organization of the human brain. This review article surveys advanced data analysis strategies developed for high-resolution fMRI at UHF. These include strategies designed to mitigate distortion and artifacts associated with higher fields in ways that attempt to preserve spatial resolution of the fMRI data, as well as recently introduced analysis techniques that are enabled by these extremely high-resolution data. Particular focus is placed on anatomically-informed analyses, including cortical surface-based analysis, which are powerful techniques that can guide each step of the analysis from preprocessing to statistical analysis to interpretation and visualization. New intracortical analysis techniques for laminar and columnar fMRI are also reviewed and discussed. Prospects for single-subject individualized analyses are also presented and discussed. Altogether, there are both specific challenges and opportunities presented by UHF-fMRI, and the use of proper analysis strategies can help these valuable data reach their full potential. Copyright © 2017 Elsevier Inc. All rights reserved.

High quality high spatial resolution functional classification in low dose dynamic CT perfusion using singular value decomposition (SVD) and k-means clustering

NASA Astrophysics Data System (ADS)

Pisana, Francesco; Henzler, Thomas; Schönberg, Stefan; Klotz, Ernst; Schmidt, Bernhard; Kachelrieß, Marc

2017-03-01

Dynamic CT perfusion acquisitions are intrinsically high-dose examinations, due to repeated scanning. To keep radiation dose under control, relatively noisy images are acquired. Noise is then further enhanced during the extraction of functional parameters from the post-processing of the time attenuation curves of the voxels (TACs) and normally some smoothing filter needs to be employed to better visualize any perfusion abnormality, but sacrificing spatial resolution. In this study we propose a new method to detect perfusion abnormalities keeping both high spatial resolution and high CNR. To do this we first perform the singular value decomposition (SVD) of the original noisy spatial temporal data matrix to extract basis functions of the TACs. Then we iteratively cluster the voxels based on a smoothed version of the three most significant singular vectors. Finally, we create high spatial resolution 3D volumes where to each voxel is assigned a distance from the centroid of each cluster, showing how functionally similar each voxel is compared to the others. The method was tested on three noisy clinical datasets: one brain perfusion case with an occlusion in the left internal carotid, one healthy brain perfusion case, and one liver case with an enhancing lesion. Our method successfully detected all perfusion abnormalities with higher spatial precision when compared to the functional maps obtained with a commercially available software. We conclude this method might be employed to have a rapid qualitative indication of functional abnormalities in low dose dynamic CT perfusion datasets. The method seems to be very robust with respect to both spatial and temporal noise and does not require any special a priori assumption. While being more robust respect to noise and with higher spatial resolution and CNR when compared to the functional maps, our method is not quantitative and a potential usage in clinical routine could be as a second reader to assist in the maps evaluation, or to guide a dataset smoothing before the modeling part.

A fast image registration approach of neural activities in light-sheet fluorescence microscopy images

NASA Astrophysics Data System (ADS)

Meng, Hui; Hui, Hui; Hu, Chaoen; Yang, Xin; Tian, Jie

2017-03-01

The ability of fast and single-neuron resolution imaging of neural activities enables light-sheet fluorescence microscopy (LSFM) as a powerful imaging technique in functional neural connection applications. The state-of-art LSFM imaging system can record the neuronal activities of entire brain for small animal, such as zebrafish or C. elegans at single-neuron resolution. However, the stimulated and spontaneous movements in animal brain result in inconsistent neuron positions during recording process. It is time consuming to register the acquired large-scale images with conventional method. In this work, we address the problem of fast registration of neural positions in stacks of LSFM images. This is necessary to register brain structures and activities. To achieve fast registration of neural activities, we present a rigid registration architecture by implementation of Graphics Processing Unit (GPU). In this approach, the image stacks were preprocessed on GPU by mean stretching to reduce the computation effort. The present image was registered to the previous image stack that considered as reference. A fast Fourier transform (FFT) algorithm was used for calculating the shift of the image stack. The calculations for image registration were performed in different threads while the preparation functionality was refactored and called only once by the master thread. We implemented our registration algorithm on NVIDIA Quadro K4200 GPU under Compute Unified Device Architecture (CUDA) programming environment. The experimental results showed that the registration computation can speed-up to 550ms for a full high-resolution brain image. Our approach also has potential to be used for other dynamic image registrations in biomedical applications.

3 Tesla MRI-detected brain lesions after pulmonary vein isolation for atrial fibrillation: results of the MACPAF study.

PubMed

Haeusler, Karl Georg; Koch, Lydia; Herm, Juliane; Kopp, Ute A; Heuschmann, Peter U; Endres, Matthias; Schultheiss, Heinz-Peter; Schirdewan, Alexander; Fiebach, Jochen B

2013-01-01

Left atrial catheter ablation (LACA) is an established therapeutic approach to abolish symptomatic atrial fibrillation (AF). Based on the prospective MACPAF study (clinicaltrials.gov NCT01061931) we report the rate of ischemic brain lesions postablation and their impact on cognitive function. Patients with symptomatic paroxysmal AF were randomized to LACA using the Arctic Front® or the HD Mesh Ablator® catheter. All patients underwent brain MRI at 3 Tesla, neurological, and neuropsychological examinations within 48 hours prior and after the ablation procedure. There was no clinically evident stroke in 37 patients (mean age 62.4 ± 8.4 years; 41% female; median CHADS2 score 1 [IQR 0-2]) after LACA but high-resolution diffusion-weighted imaging (DWI) detected new ischemic lesions in 15 (41%) patients after LACA. Four (27%) of the HD Mesh Ablator® patients and 11 (50%) of the Arctic Front® patients suffered a silent ischemic lesion (P = 0.19). In these 15 patients, there was a nonsignificant trend toward lower cardiac ejection fraction (P = 0.07) and AF episodes during LACA (P = 0.09), while activated clotting time levels, number of energy applications, periprocedural electrocardioversion or CHADS(2) score had no impact. Lesion volumes varied from 5 to 150 mm(3) and 1 to 5 lesions were detected per patient. However, acute brain lesions had no effect on cognitive performance immediately after LACA. Of the DWI lesions postablation 82% were not detectable on FLAIR images 6-9 months postablation. According to 3 Tesla high-resolution DWI, ischemic brain lesions after LACA were common but not associated with impaired cognitive function after the ablation procedure. © 2012 Wiley Periodicals, Inc.

Lithium Visibility in Rat Brain and Muscle in Vivoby 7Li NMR Imaging

NASA Astrophysics Data System (ADS)

Komoroski, Richard A.; Pearce, John M.; Newton, Joseph E. O.

1998-07-01

The apparent concentration of lithium (Li)in vivowas determined for several regions in the brain and muscle of rats by7Li NMR imaging at 4.7 T with inclusion of an external standard of known concentration and visibility. The average apparent concentrations were 10.1 mM for muscle, and 4.2-5.3 mM for various brain regions under the dosing conditions used. The results were compared to concentrations determinedin vitroby high-resolution7Li NMR spectroscopy of extracts of brain and muscle tissue from the same rats. The comparison provided estimates of the7Li NMR visibility of the Li cation in each tissue region. Although there was considerable scatter of the calculated visibilities among the five rats studied, the results suggested essentially full visibility (96%) for Li in muscle, and somewhat reduced visibility (74-93%) in the various brain regions.

Brain morphometry in blind and sighted subjects.

PubMed

Maller, Jerome J; Thomson, Richard H; Ng, Amanda; Mann, Collette; Eager, Michael; Ackland, Helen; Fitzgerald, Paul B; Egan, Gary; Rosenfeld, Jeffrey V

2016-11-01

Previous neuroimaging studies have demonstrated structural brain alterations in blind subjects, but most have focused on primary open angle glaucoma or retinopathy of prematurity, used low-field scanners, a limited number of receive channels, or have presented uncorrected results. We recruited 10 blind and 10 age and sex-matched controls to undergo high-resolution MRI using a 3T scanner and a 32-channel receive coil. We evaluated whole-brain morphological differences between the groups as well as manual segmentation of regional hippocampal volumes. There were no hippocampal volume differences between the groups. Whole-brain morphometry showed white matter volume differences between blind and sighted groups including localised larger regions in the visual cortex (occipital gyral volume and thickness) among those with blindness early in life compared to those with blindness later in life. Hence, in our patients, blindness resulted in brain volumetric differences that depend upon duration of blindness. Copyright © 2016 Elsevier Ltd. All rights reserved.

Arterial Spin Labeling: a one-stop-shop for measurement of brain perfusion in the clinical settings.

PubMed

Golay, Xavier; Petersen, Esben T; Zimine, Ivan; Lim, Tchoyoson C C

2007-01-01

Arterial Spin Labeling (ASL) has opened a unique window into the human brain function and perfusion physiology. Altogether fast and of intrinsic high spatial resolution, ASL is a technique very appealing not only for the diagnosis of vascular diseases, but also in basic neuroscience for the follow-up of small perfusion changes occurring during brain activation. However, due to limited signal-to-noise ratio and complex flow kinetics, ASL is one of the more challenging disciplines within magnetic resonance imaging. In this paper, the theoretical background and main implementations of ASL are revisited. In particular, the different uses of ASL, the pitfalls and possibilities are described and illustrated using clinical cases.

Heterogeneous data fusion for brain tumor classification.

PubMed

Metsis, Vangelis; Huang, Heng; Andronesi, Ovidiu C; Makedon, Fillia; Tzika, Aria

2012-10-01

Current research in biomedical informatics involves analysis of multiple heterogeneous data sets. This includes patient demographics, clinical and pathology data, treatment history, patient outcomes as well as gene expression, DNA sequences and other information sources such as gene ontology. Analysis of these data sets could lead to better disease diagnosis, prognosis, treatment and drug discovery. In this report, we present a novel machine learning framework for brain tumor classification based on heterogeneous data fusion of metabolic and molecular datasets, including state-of-the-art high-resolution magic angle spinning (HRMAS) proton (1H) magnetic resonance spectroscopy and gene transcriptome profiling, obtained from intact brain tumor biopsies. Our experimental results show that our novel framework outperforms any analysis using individual dataset.

Super-resolution reconstruction of diffusion parameters from diffusion-weighted images with different slice orientations.

PubMed

Van Steenkiste, Gwendolyn; Jeurissen, Ben; Veraart, Jelle; den Dekker, Arnold J; Parizel, Paul M; Poot, Dirk H J; Sijbers, Jan

2016-01-01

Diffusion MRI is hampered by long acquisition times, low spatial resolution, and a low signal-to-noise ratio. Recently, methods have been proposed to improve the trade-off between spatial resolution, signal-to-noise ratio, and acquisition time of diffusion-weighted images via super-resolution reconstruction (SRR) techniques. However, during the reconstruction, these SRR methods neglect the q-space relation between the different diffusion-weighted images. An SRR method that includes a diffusion model and directly reconstructs high resolution diffusion parameters from a set of low resolution diffusion-weighted images was proposed. Our method allows an arbitrary combination of diffusion gradient directions and slice orientations for the low resolution diffusion-weighted images, optimally samples the q- and k-space, and performs motion correction with b-matrix rotation. Experiments with synthetic data and in vivo human brain data show an increase of spatial resolution of the diffusion parameters, while preserving a high signal-to-noise ratio and low scan time. Moreover, the proposed SRR method outperforms the previous methods in terms of the root-mean-square error. The proposed SRR method substantially increases the spatial resolution of MRI that can be obtained in a clinically feasible scan time. © 2015 Wiley Periodicals, Inc.

4D MEMRI atlas of neonatal FVB/N mouse brain development.

PubMed

Szulc, Kamila U; Lerch, Jason P; Nieman, Brian J; Bartelle, Benjamin B; Friedel, Miriam; Suero-Abreu, Giselle A; Watson, Charles; Joyner, Alexandra L; Turnbull, Daniel H

2015-09-01

The widespread use of the mouse as a model system to study brain development has created the need for noninvasive neuroimaging methods that can be applied to early postnatal mice. The goal of this study was to optimize in vivo three- (3D) and four-dimensional (4D) manganese (Mn)-enhanced MRI (MEMRI) approaches for acquiring and analyzing data from the developing mouse brain. The combination of custom, stage-dependent holders and self-gated (motion-correcting) 3D MRI sequences enabled the acquisition of high-resolution (100-μm isotropic), motion artifact-free brain images with a high level of contrast due to Mn-enhancement of numerous brain regions and nuclei. We acquired high-quality longitudinal brain images from two groups of FVB/N strain mice, six mice per group, each mouse imaged on alternate odd or even days (6 3D MEMRI images at each day) covering the developmental stages between postnatal days 1 to 11. The effects of Mn-exposure, anesthesia and MRI were assessed, showing small but significant transient effects on body weight and brain volume, which recovered with time and did not result in significant morphological differences when compared to controls. Metrics derived from deformation-based morphometry (DBM) were used for quantitative analysis of changes in volume and position of a number of brain regions. The cerebellum, a brain region undergoing significant changes in size and patterning at early postnatal stages, was analyzed in detail to demonstrate the spatiotemporal characterization made possible by this new atlas of mouse brain development. These results show that MEMRI is a powerful tool for quantitative analysis of mouse brain development, with great potential for in vivo phenotype analysis in mouse models of neurodevelopmental diseases. Copyright © 2015 Elsevier Inc. All rights reserved.

High-resolution imaging-guided electroencephalography source localization: temporal effect regularization incorporation in LORETA inverse solution

NASA Astrophysics Data System (ADS)

Boughariou, Jihene; Zouch, Wassim; Slima, Mohamed Ben; Kammoun, Ines; Hamida, Ahmed Ben

2015-11-01

Electroencephalography (EEG) and magnetic resonance imaging (MRI) are noninvasive neuroimaging modalities. They are widely used and could be complementary. The fusion of these modalities may enhance some emerging research fields targeting the exploration better brain activities. Such research attracted various scientific investigators especially to provide a convivial and helpful advanced clinical-aid tool enabling better neurological explorations. Our present research was, in fact, in the context of EEG inverse problem resolution and investigated an advanced estimation methodology for the localization of the cerebral activity. Our focus was, therefore, on the integration of temporal priors to low-resolution brain electromagnetic tomography (LORETA) formalism and to solve the inverse problem in the EEG. The main idea behind our proposed method was in the integration of a temporal projection matrix within the LORETA weighting matrix. A hyperparameter is the principal fact for such a temporal integration, and its importance would be obvious when obtaining a regularized smoothness solution. Our experimental results clearly confirmed the impact of such an optimization procedure adopted for the temporal regularization parameter comparatively to the LORETA method.

In vivo quantification of T2* anisotropy in white matter fibers in marmoset monkeys

PubMed Central

Sati, P.; Silva, A. C.; van Gelderen, P.; Gaitan, M. I.; Wohler, J. E.; Jacobson, S.; Duyn, J. H.; Reich, D. S.

2011-01-01

T2*-weighted MRI at high field is a promising approach for studying noninvasively the tissue structure and composition of the brain. However, the biophysical origin of T2* contrast, especially in white matter, remains poorly understood. Recent work has shown that R2* (=1/T2*) may depend on the tissue’s orientation relative to the static magnetic field (B0) and suggested that this dependence could be attributed to local anisotropy in the magnetic properties of brain tissue. In the present work, we analyzed high-resolution, multi-gradient-echo images of in vivo marmoset brains at 7T, and compared them with ex vivo diffusion tensor images, to show that R2* relaxation in white matter is highly sensitive to the fiber orientation relative to the main field. We directly demonstrate this orientation dependence by performing in vivo multi-gradient-echo acquisitions in two orthogonal brain positions, uncovering a nearly 50% change in the R2*relaxation rate constant of the optic radiations. We attribute this substantial R2* anisotropy to local subvoxel susceptibility effects arising from the highly ordered and anisotropic structure of the myelin sheath. PMID:21906687

Neural systems and time course of proactive interference in working memory.

PubMed

Du, Yingchun; Zhang, John X; Xiao, Zhuangwei; Wu, Renhua

2007-01-01

The storage of information in working memory suffers as a function of proactive interference. Many works using neuroimaging technique have been done to reveal the brain mechanism of interference resolution. However, less is yet known about the time course of this process. Event-related potential method(ERP) and standardized Low Resolution Brain Electromagnetic Tomography method (sLORETA) were used in this study to discover the time course of interference resolution in working memory. The anterior P2 was thought to reflect interference resolution and if so, this process occurred earlier in working memory than in long-term memory.

Development and characterization of non-resonant multiphoton photoacoustic spectroscopy (NMPPAS) for brain tumor margining

NASA Astrophysics Data System (ADS)

Dahal, Sudhir

During tumor removal surgery, due to the problems associated with obtaining high-resolution, real-time chemical images of where exactly the tumor ends and healthy tissue begins (tumor margining), it is often necessary to remove a much larger volume of tissue than the tumor itself. In the case of brain tumor surgery, however, it is extremely unsafe to remove excess tissue. Therefore, without an accurate image of the tumor margins, some of the tumor's finger-like projections are inevitably left behind in the surrounding parenchyma to grow again. For this reason, the development of techniques capable of providing high-resolution real-time images of tumor margins up to centimeters below the surface of a tissue is ideal for the diagnosis and treatment of tumors, as well as surgical guidance during brain tumor excision. A novel spectroscopic technique, non-resonant multiphoton photoacoustic spectroscopy (NMPPAS), is being developed with the capabilities of obtaining high-resolution subsurface chemical-based images of underlying tumors. This novel technique combines the strengths of multiphoton tissue spectroscopy and photoacoustic spectroscopy into a diagnostic methodology that will, ultimately, provide unparalleled chemical information and images to provide the state of sub-surface tissues. The NMPPAS technique employs near-infrared light (in the diagnostic window) to excite ultraviolet and/or visible light absorbing species deep below the tissue's surface. Once a multiphoton absorption event occurs, non-radiative relaxation processes generates a localized thermal expansion and subsequent acoustic wave that can be detected using a piezoelectric transducer. Since NMPPAS employs an acoustic detection modality, much deeper diagnoses can be performed than that is possible using current state of the art high-resolution chemical imaging techniques such as multiphoton fluorescence spectroscopy. NMPPAS was employed to differentiate between excised brain tumors (astrocytoma III) and healthy tissue with over 99% accuracy. NMPPAS spectral features showed evident differences between tumor and healthy tissues, and ratiometric analysis ensured that only a few wavelengths could be used for excitation instead of using numerous wavelength excitations to create spectra. This process would significantly reduce the analysis time while maintaining the same degree of accuracy. Tissue phantoms were fabricated in order to characterize the properties of NMPPAS. Scattering particles were doped into the phantoms to simulate their light scattering properties to real tissues. This allowed for better control over shape, size, reproducibility and doping in the sample while maintaining the light-tissue interaction properties of real tissue. To make NMPPAS viable for clinical applications, the technique was characterized to determine the spatial (lateral and longitudinal) resolution, depth of penetration and its ability to image in three-dimension through layers of tissue. Both resolutions were determined to be near-cellular level resolution (50-70 microm), obtained initially with the aid of the technique of multiphoton fluorescence, and later verified using NMPPAS imaging. Additionally, the maximum depth of penetration and detection was determined to be about 1.4cm, making the technique extremely suitable to margin tumors from underlying tissues in the brain. The capability of NMPPAS to detect and image layers that lie beneath other structures and blood vessels was also investigated. Three-dimensional images were obtained for the first time using NMPPAS. The images were obtained from different depths and structures were imaged through other layers of existing structures in the sample. This verified that NMPPAS was capable of detecting and imaging structures that lie embedded within the tissues. NMPPAS images of embedded structures were also obtained with the presence of hemoglobin, which is potentially the largest source of background in blood-perfused tissues, thus showing that the technique is capable of detecting and differentiating in blood-perfused samples.

An implanted 8-channel array coil for high-resolution macaque MRI at 3T

PubMed Central

Janssens, T.; Keil, B.; Farivar, R.; McNab, J.A.; Polimeni, J. R.; Gerits, A.; Arsenault, J.T.; Wald, L. L.; Vanduffel, W.

2012-01-01

An 8-channel receive coil array was constructed and implanted adjacent to the skull in a male rhesus monkey in order to improve the sensitivity of (functional) brain imaging. The permanent implant was part of an acrylic headpost assembly and only the coil element loop wires were implanted. The tuning, matching, and preamplifier circuitry was connected via a removable external assembly. Signal-to-noise ratio (SNR) and noise amplification for parallel imaging were compared to a single-, 4-, and 8-channel external receive-only coil routinely used for macaque fMRI. In vivo measurements showed significantly improved SNR within the brain for the implanted versus the external coils. Within a region-of-interest covering the cerebral cortex, we observed a 5.4-, 3.6-fold, and 3.4-fold increase in SNR compared to the external single-, 4-, and 8-channel coil, respectively. In the center of the brain, the implanted array maintained a 2.4×, 2.5×, and 2.1× higher SNR, respectively compared to the external coils. The array performance was evaluated for anatomical, diffusion tensor and functional brain imaging. This study suggests that a stable implanted phased-array coil can be used in macaque MRI to substantially increase the spatial resolution for anatomical, diffusion tensor, and functional imaging. PMID:22609793

Direct mapping of 19F in 19FDG-6P in brain tissue at subcellular resolution using soft X-ray fluorescence

NASA Astrophysics Data System (ADS)

Poitry-Yamate, C.; Gianoncelli, A.; Kourousias, G.; Kaulich, B.; Lepore, M.; Gruetter, R.; Kiskinova, M.

2013-10-01

Low energy x-ray fluorescence (LEXRF) detection was optimized for imaging cerebral glucose metabolism by mapping the fluorine LEXRF signal of 19F in 19FDG, trapped as intracellular 19F-deoxyglucose-6-phosphate (19FDG-6P) at 1μm spatial resolution from 3μm thick brain slices. 19FDG metabolism was evaluated in brain structures closely resembling the general cerebral cytoarchitecture following formalin fixation of brain slices and their inclusion in an epon matrix. 2-dimensional distribution maps of 19FDG-6P were placed in a cytoarchitectural and morphological context by simultaneous LEXRF mapping of N and O, and scanning transmission x-ray (STXM) imaging. A disproportionately high uptake and metabolism of glucose was found in neuropil relative to intracellular domains of the cell body of hypothalamic neurons, showing directly that neurons, like glial cells, also metabolize glucose. As 19F-deoxyglucose-6P is structurally identical to 18F-deoxyglucose-6P, LEXRF of subcellular 19F provides a link to in vivo 18FDG PET, forming a novel basis for understanding the physiological mechanisms underlying the 18FDG PET image, and the contribution of neurons and glia to the PET signal.

Fast periodic stimulation (FPS): a highly effective approach in fMRI brain mapping.

PubMed

Gao, Xiaoqing; Gentile, Francesco; Rossion, Bruno

2018-06-01

Defining the neural basis of perceptual categorization in a rapidly changing natural environment with low-temporal resolution methods such as functional magnetic resonance imaging (fMRI) is challenging. Here, we present a novel fast periodic stimulation (FPS)-fMRI approach to define face-selective brain regions with natural images. Human observers are presented with a dynamic stream of widely variable natural object images alternating at a fast rate (6 images/s). Every 9 s, a short burst of variable face images contrasting with object images in pairs induces an objective face-selective neural response at 0.111 Hz. A model-free Fourier analysis achieves a twofold increase in signal-to-noise ratio compared to a conventional block-design approach with identical stimuli and scanning duration, allowing to derive a comprehensive map of face-selective areas in the ventral occipito-temporal cortex, including the anterior temporal lobe (ATL), in all individual brains. Critically, periodicity of the desired category contrast and random variability among widely diverse images effectively eliminates the contribution of low-level visual cues, and lead to the highest values (80-90%) of test-retest reliability in the spatial activation map yet reported in imaging higher level visual functions. FPS-fMRI opens a new avenue for understanding brain function with low-temporal resolution methods.

SAR and scan-time optimized 3D whole-brain double inversion recovery imaging at 7T.

PubMed

Pracht, Eberhard D; Feiweier, Thorsten; Ehses, Philipp; Brenner, Daniel; Roebroeck, Alard; Weber, Bernd; Stöcker, Tony

2018-05-01

The aim of this project was to implement an ultra-high field (UHF) optimized double inversion recovery (DIR) sequence for gray matter (GM) imaging, enabling whole brain coverage in short acquisition times ( ≈5 min, image resolution 1 mm 3 ). A 3D variable flip angle DIR turbo spin echo (TSE) sequence was optimized for UHF application. We implemented an improved, fast, and specific absorption rate (SAR) efficient TSE imaging module, utilizing improved reordering. The DIR preparation was tailored to UHF application. Additionally, fat artifacts were minimized by employing water excitation instead of fat saturation. GM images, covering the whole brain, were acquired in 7 min scan time at 1 mm isotropic resolution. SAR issues were overcome by using a dedicated flip angle calculation considering SAR and SNR efficiency. Furthermore, UHF related artifacts were minimized. The suggested sequence is suitable to generate GM images with whole-brain coverage at UHF. Due to the short total acquisition times and overall robustness, this approach can potentially enable DIR application in a routine setting and enhance lesion detection in neurological diseases. Magn Reson Med 79:2620-2628, 2018. © 2017 International Society for Magnetic Resonance in Medicine. © 2017 International Society for Magnetic Resonance in Medicine.

Clinical progression and outcome of dysphagia following paediatric traumatic brain injury: a prospective study.

PubMed

Morgan, Angela; Ward, Elizabeth; Murdoch, Bruce

2004-04-01

To provide a preliminary clinical profile of the resolution and outcomes of oral-motor impairment and swallowing function in a group of paediatric dysphagia patients post-traumatic brain injury (TBI). To document the level of cognitive impairment parallel to the return to oral intake, and to investigate the correlation between the resolution of impaired swallow function versus the resolution of oral-motor impairment and cognitive impairment. Thirteen children admitted to an acute care setting for TBI. A series of oral-motor (Verbal Motor Production Assessment for Children, Frenchay Dysarthria Assessment, Schedule for Oral Motor Assessment) and swallowing (Paramatta Hospital's Assessment for Dysphagia) assessments, an outcome measure for swallowing (Royal Brisbane Hospital's Outcome Measure for Swallowing), and a cognitive rating scale (Rancho Level of Cognitive Functioning Scale). Across the patient group, oral-motor deficits resolved to normal status between 3 and 11 weeks post-referral (and at an average of 12 weeks post-injury) and swallowing function and resolution to normal diet status were achieved by 3-11 weeks post-referral (and at an average of 12 weeks post-injury). The resolution of dysphagia and the resolution of oral-motor impairment and cognitive impairment were all highly correlated. The provision of a preliminary profile of oral-motor functioning and dysphagia resolution, and data on the linear relationship between swallowing impairment and cognition, will provide baseline information on the course of rehabilitation of dysphagia in the paediatric population post-TBI. Such data will contribute to more informed service provision and rehabilitation planning for paediatric patients post-TBI.

Novel methodology to characterize electromagnetic exposure of the brain

NASA Astrophysics Data System (ADS)

Crespo-Valero, Pedro; Christopoulou, Maria; Zefferer, Marcel; Christ, Andreas; Achermann, Peter; Nikita, Konstantina S.; Kuster, Niels

2011-01-01

Due to the greatly non-uniform field distribution induced in brain tissues by radio frequency electromagnetic sources, the exposure of anatomical and functional regions of the brain may be a key issue in interpreting laboratory findings and epidemiological studies concerning endpoints related to the central nervous system. This paper introduces the Talairach atlas in characterization of the electromagnetic exposure of the brain. A hierarchical labeling scheme is mapped onto high-resolution human models. This procedure is fully automatic and allows identification of over a thousand different sites all over the brain. The electromagnetic absorption can then be extracted and interpreted in every region or combination of regions in the brain, depending on the characterization goals. The application examples show how this methodology enhances the dosimetry assessment of the brain based on results obtained by either finite difference time domain simulations or measurements delivered by test compliance dosimetry systems. Applications include, among others, the detailed dosimetric analysis of the exposure of the brain during cell phone use, improved design of exposure setups for human studies or medical diagnostic and therapeutic devices using electromagnetic fields or ultrasound.

Nutritional Cognitive Neuroscience: Innovations for Healthy Brain Aging.

PubMed

Zamroziewicz, Marta K; Barbey, Aron K

2016-01-01

Nutritional cognitive neuroscience is an emerging interdisciplinary field of research that seeks to understand nutrition's impact on cognition and brain health across the life span. Research in this burgeoning field demonstrates that many aspects of nutrition-from entire diets to specific nutrients-affect brain structure and function, and therefore have profound implications for understanding the nature of healthy brain aging. The aim of this Focused Review is to examine recent advances in nutritional cognitive neuroscience, with an emphasis on methods that enable discovery of nutrient biomarkers that predict healthy brain aging. We propose an integrative framework that calls for the synthesis of research in nutritional epidemiology and cognitive neuroscience, incorporating: (i) methods for the precise characterization of nutritional health based on the analysis of nutrient biomarker patterns (NBPs), along with (ii) modern indices of brain health derived from high-resolution magnetic resonance imaging (MRI). By integrating cutting-edge techniques from nutritional epidemiology and cognitive neuroscience, nutritional cognitive neuroscience will continue to advance our understanding of the beneficial effects of nutrition on the aging brain and establish effective nutritional interventions to promote healthy brain aging.

Multimodal Approaches to Define Network Oscillations in Depression

PubMed Central

Smart, Otis Lkuwamy; Tiruvadi, Vineet Ravi; Mayberg, Helen S.

2018-01-01

The renaissance in the use of encephalography-based research methods to probe the pathophysiology of neuropsychiatric disorders is well afoot and continues to advance. Building on the platform of neuroimaging evidence on brain circuit models, magnetoencephalography, scalp electroencephalography, and even invasive electroencephalography are now being used to characterize brain network dysfunctions that underlie major depressive disorder using brain oscillation measurements and associated treatment responses. Such multiple encephalography modalities provide avenues to study pathologic network dynamics with high temporal resolution and over long time courses, opportunities to complement neuroimaging methods and findings, and new approaches to identify quantitative biomarkers that indicate critical targets for brain therapy. Such goals have been facilitated by the ongoing testing of novel invasive neuromodulation therapies, notably, deep brain stimulation, where clinically relevant treatment effects can be monitored at multiple brain sites in a time-locked causal manner. We review key brain rhythms identified in major depressive disorder as foundation for development of putative biomarkers for objectively evaluating neuromodulation success and for guiding deep brain stimulation or other target-based neuromodulation strategies for treatment-resistant depression patients. PMID:25681871

Nutritional Cognitive Neuroscience: Innovations for Healthy Brain Aging

PubMed Central

Zamroziewicz, Marta K.; Barbey, Aron K.

2016-01-01

Nutritional cognitive neuroscience is an emerging interdisciplinary field of research that seeks to understand nutrition's impact on cognition and brain health across the life span. Research in this burgeoning field demonstrates that many aspects of nutrition—from entire diets to specific nutrients—affect brain structure and function, and therefore have profound implications for understanding the nature of healthy brain aging. The aim of this Focused Review is to examine recent advances in nutritional cognitive neuroscience, with an emphasis on methods that enable discovery of nutrient biomarkers that predict healthy brain aging. We propose an integrative framework that calls for the synthesis of research in nutritional epidemiology and cognitive neuroscience, incorporating: (i) methods for the precise characterization of nutritional health based on the analysis of nutrient biomarker patterns (NBPs), along with (ii) modern indices of brain health derived from high-resolution magnetic resonance imaging (MRI). By integrating cutting-edge techniques from nutritional epidemiology and cognitive neuroscience, nutritional cognitive neuroscience will continue to advance our understanding of the beneficial effects of nutrition on the aging brain and establish effective nutritional interventions to promote healthy brain aging. PMID:27375409

Toward the holistic, reference, and extendable atlas of the human brain, head, and neck.

PubMed

Nowinski, Wieslaw L

2015-06-01

Despite numerous efforts, a fairly complete (holistic) anatomical model of the whole, normal, adult human brain, which is required as the reference in brain studies and clinical applications, has not yet been constructed. Our ultimate objective is to build this kind of atlas from advanced in vivo imaging. This work presents the taxonomy of our currently developed brain atlases and addresses the design, content, functionality, and current results in the holistic atlas development as well as atlas usefulness and future directions. We have developed to date 35 commercial brain atlases (along with numerous research prototypes), licensed to 63 companies and institutions, and made available to medical societies, organizations, medical schools, and individuals. These atlases have been applied in education, research, and clinical applications. Hundreds of thousands of patients have been treated by using our atlases. Based on this experience, the first version of the holistic and reference atlas of the brain, head, and neck has been developed and made available. The atlas has been created from multispectral 3 and 7 Tesla and high-resolution CT in vivo scans. It is fully 3D, scalable, interactive, and highly detailed with about 3,000 labeled components. This atlas forms a foundation for the development of a multi-level molecular, cellular, anatomical, physiological, and behavioral brain atlas platform.

Improving Axial Resolution in Confocal Microscopy with New High Refractive Index Mounting Media

PubMed Central

Fouquet, Coralie; Gilles, Jean-François; Heck, Nicolas; Dos Santos, Marc; Schwartzmann, Richard; Cannaya, Vidjeacoumary; Morel, Marie-Pierre; Davidson, Robert Stephen; Trembleau, Alain; Bolte, Susanne

2015-01-01

Resolution, high signal intensity and elevated signal to noise ratio (SNR) are key issues for biologists who aim at studying the localisation of biological structures at the cellular and subcellular levels using confocal microscopy. The resolution required to separate sub-cellular biological structures is often near to the resolving power of the microscope. When optimally used, confocal microscopes may reach resolutions of 180 nm laterally and 500 nm axially, however, axial resolution in depth is often impaired by spherical aberration that may occur due to refractive index mismatches. Spherical aberration results in broadening of the point-spread function (PSF), a decrease in peak signal intensity when imaging in depth and a focal shift that leads to the distortion of the image along the z-axis and thus in a scaling error. In this study, we use the novel mounting medium CFM3 (Citifluor Ltd., UK) with a refractive index of 1.518 to minimize the effects of spherical aberration. This mounting medium is compatible with most common fluorochromes and fluorescent proteins. We compare its performance with established mounting media, harbouring refractive indices below 1.500, by estimating lateral and axial resolution with sub-resolution fluorescent beads. We show furthermore that the use of the high refractive index media renders the tissue transparent and improves considerably the axial resolution and imaging depth in immuno-labelled or fluorescent protein labelled fixed mouse brain tissue. We thus propose to use those novel high refractive index mounting media, whenever optimal axial resolution is required. PMID:25822785

Development and Implementation of a Corriedale Ovine Brain Atlas for Use in Atlas-Based Segmentation.

PubMed

Liyanage, Kishan Andre; Steward, Christopher; Moffat, Bradford Armstrong; Opie, Nicholas Lachlan; Rind, Gil Simon; John, Sam Emmanuel; Ronayne, Stephen; May, Clive Newton; O'Brien, Terence John; Milne, Marjorie Eileen; Oxley, Thomas James

2016-01-01

Segmentation is the process of partitioning an image into subdivisions and can be applied to medical images to isolate anatomical or pathological areas for further analysis. This process can be done manually or automated by the use of image processing computer packages. Atlas-based segmentation automates this process by the use of a pre-labelled template and a registration algorithm. We developed an ovine brain atlas that can be used as a model for neurological conditions such as Parkinson's disease and focal epilepsy. 17 female Corriedale ovine brains were imaged in-vivo in a 1.5T (low-resolution) MRI scanner. 13 of the low-resolution images were combined using a template construction algorithm to form a low-resolution template. The template was labelled to form an atlas and tested by comparing manual with atlas-based segmentations against the remaining four low-resolution images. The comparisons were in the form of similarity metrics used in previous segmentation research. Dice Similarity Coefficients were utilised to determine the degree of overlap between eight independent, manual and atlas-based segmentations, with values ranging from 0 (no overlap) to 1 (complete overlap). For 7 of these 8 segmented areas, we achieved a Dice Similarity Coefficient of 0.5-0.8. The amygdala was difficult to segment due to its variable location and similar intensity to surrounding tissues resulting in Dice Coefficients of 0.0-0.2. We developed a low resolution ovine brain atlas with eight clinically relevant areas labelled. This brain atlas performed comparably to prior human atlases described in the literature and to intra-observer error providing an atlas that can be used to guide further research using ovine brains as a model and is hosted online for public access.

Compartmentalized Low-Rank Recovery for High-Resolution Lipid Unsuppressed MRSI

PubMed Central

Bhattacharya, Ipshita; Jacob, Mathews

2017-01-01

Purpose To introduce a novel algorithm for the recovery of high-resolution magnetic resonance spectroscopic imaging (MRSI) data with minimal lipid leakage artifacts, from dual-density spiral acquisition. Methods The reconstruction of MRSI data from dual-density spiral data is formulated as a compartmental low-rank recovery problem. The MRSI dataset is modeled as the sum of metabolite and lipid signals, each of which is support limited to the brain and extracranial regions, respectively, in addition to being orthogonal to each other. The reconstruction problem is formulated as an optimization problem, which is solved using iterative reweighted nuclear norm minimization. Results The comparisons of the scheme against dual-resolution reconstruction algorithm on numerical phantom and in vivo datasets demonstrate the ability of the scheme to provide higher spatial resolution and lower lipid leakage artifacts. The experiments demonstrate the ability of the scheme to recover the metabolite maps, from lipid unsuppressed datasets with echo time (TE)=55 ms. Conclusion The proposed reconstruction method and data acquisition strategy provide an efficient way to achieve high-resolution metabolite maps without lipid suppression. This algorithm would be beneficial for fast metabolic mapping and extension to multislice acquisitions. PMID:27851875

Isolated brain stem lesion in children: is it acute disseminated encephalomyelitis or not?

PubMed

Alper, G; Sreedher, G; Zuccoli, G

2013-01-01

Isolated brain stem lesions presenting with acute neurologic findings create a major diagnostic dilemma in children. Although the brain stem is frequently involved in ADEM, solitary brain stem lesions are unusual. We performed a retrospective review in 6 children who presented with an inflammatory lesion confined to the brain stem. Two children were diagnosed with connective tissue disorder, CNS lupus, and localized scleroderma. The etiology could not be determined in 1, and clinical features suggested monophasic demyelination in 3. In these 3 children, initial lesions demonstrated vasogenic edema; all showed dramatic response to high-dose corticosteroids and made a full clinical recovery. Follow-up MRI showed complete resolution of lesions, and none had relapses at >2 years of follow-up. In retrospect, these cases are best regarded as a localized form of ADEM. We conclude that though ADEM is typically a disseminated disease with multifocal lesions, it rarely presents with monofocal demyelination confined to the brain stem.

Towards deep brain monitoring with superficial EEG sensors plus neuromodulatory focused ultrasound

PubMed Central

Darvas, F; Mehić, E; Caler, CJ; Ojemann, JG; Mourad, PD

2017-01-01

Noninvasive recordings of electrophysiological activity have limited anatomical specificity and depth. We hypothesized that spatially tagging a small volume of brain with a unique electroencephalogram (EEG) signal induced by pulsed focused ultrasound (pFU) could overcome those limitations. As a first step towards testing this hypothesis, we applied transcranial ultrasound (2 MHz, 200 microsecond-long pulses applied at 1050 Hz for one second at a spatial peak temporal average intensity of 1.4 W/cm2) to the brains of anesthetized rats while simultaneously recording EEG signals. We observed a significant 1050 Hz electrophysiological signal only when ultrasound was applied to living brain. Moreover, amplitude demodulation of the EEG signal at 1050 Hz yielded measurement of gamma band (>30 Hz) brain activity consistent with direct measurements of that activity. These results represent preliminary support for use of pFU as a spatial tagging mechanism for non-invasive EEG-based mapping of deep brain activity with high spatial resolution. PMID:27181686

The influence of sex steroids on structural brain maturation in adolescence.

PubMed

Koolschijn, P Cédric M P; Peper, Jiska S; Crone, Eveline A

2014-01-01

Puberty reflects a period of hormonal changes, physical maturation and structural brain reorganization. However, little attention has been paid to what extent sex steroids and pituitary hormones are associated with the refinement of brain maturation across adolescent development. Here we used high-resolution structural MRI scans from 215 typically developing individuals between ages 8-25, to examine the association between cortical thickness, surface area and (sub)cortical brain volumes with luteinizing hormone, testosterone and estradiol, and pubertal stage based on self-reports. Our results indicate sex-specific differences in testosterone related influences on gray matter volumes of the anterior cingulate cortex after controlling for age effects. No significant associations between subcortical structures and sex hormones were found. Pubertal stage was not a stronger predictor than chronological age for brain anatomical differences. Our findings indicate that sex steroids are associated with cerebral gray matter morphology in a sex specific manner. These hormonal and morphological differences may explain in part differences in brain development between boys and girls.

Mapping of Brain Activity by Automated Volume Analysis of Immediate Early Genes.

PubMed

Renier, Nicolas; Adams, Eliza L; Kirst, Christoph; Wu, Zhuhao; Azevedo, Ricardo; Kohl, Johannes; Autry, Anita E; Kadiri, Lolahon; Umadevi Venkataraju, Kannan; Zhou, Yu; Wang, Victoria X; Tang, Cheuk Y; Olsen, Olav; Dulac, Catherine; Osten, Pavel; Tessier-Lavigne, Marc

2016-06-16

Understanding how neural information is processed in physiological and pathological states would benefit from precise detection, localization, and quantification of the activity of all neurons across the entire brain, which has not, to date, been achieved in the mammalian brain. We introduce a pipeline for high-speed acquisition of brain activity at cellular resolution through profiling immediate early gene expression using immunostaining and light-sheet fluorescence imaging, followed by automated mapping and analysis of activity by an open-source software program we term ClearMap. We validate the pipeline first by analysis of brain regions activated in response to haloperidol. Next, we report new cortical regions downstream of whisker-evoked sensory processing during active exploration. Last, we combine activity mapping with axon tracing to uncover new brain regions differentially activated during parenting behavior. This pipeline is widely applicable to different experimental paradigms, including animal species for which transgenic activity reporters are not readily available. Copyright © 2016 Elsevier Inc. All rights reserved.

Mapping of brain activity by automated volume analysis of immediate early genes

PubMed Central

Renier, Nicolas; Adams, Eliza L.; Kirst, Christoph; Wu, Zhuhao; Azevedo, Ricardo; Kohl, Johannes; Autry, Anita E.; Kadiri, Lolahon; Venkataraju, Kannan Umadevi; Zhou, Yu; Wang, Victoria X.; Tang, Cheuk Y.; Olsen, Olav; Dulac, Catherine; Osten, Pavel; Tessier-Lavigne, Marc

2016-01-01

Summary Understanding how neural information is processed in physiological and pathological states would benefit from precise detection, localization and quantification of the activity of all neurons across the entire brain, which has not to date been achieved in the mammalian brain. We introduce a pipeline for high speed acquisition of brain activity at cellular resolution through profiling immediate early gene expression using immunostaining and light-sheet fluorescence imaging, followed by automated mapping and analysis of activity by an open-source software program we term ClearMap. We validate the pipeline first by analysis of brain regions activated in response to Haloperidol. Next, we report new cortical regions downstream of whisker-evoked sensory processing during active exploration. Lastly, we combine activity mapping with axon tracing to uncover new brain regions differentially activated during parenting behavior. This pipeline is widely applicable to different experimental paradigms, including animal species for which transgenic activity reporters are not readily available. PMID:27238021

Gold nanoparticle imaging and radiotherapy of brain tumors in mice

PubMed Central

Hainfeld, James F; Smilowitz, Henry M; O'Connor, Michael J; Dilmanian, Farrokh Avraham; Slatkin, Daniel N

2013-01-01

Aim To test intravenously injected gold nanoparticles for x-ray imaging and radiotherapy enhancement of large, imminently lethal, intracerebral malignant gliomas. Materials & methods Gold nanoparticles approximately 11 nm in size were injected intravenously and brains imaged using microcomputed tomography. A total of 15 h after an intravenous dose of 4 g Au/kg was administered, brains were irradiated with 30 Gy 100 kVp x-rays. Results Gold uptake gave a 19:1 tumor-to-normal brain ratio with 1.5% w/w gold in tumor, calculated to increase local radiation dose by approximately 300%. Mice receiving gold and radiation (30 Gy) demonstrated 50% long term (>1 year) tumor-free survival, whereas all mice receiving radiation only died. Conclusion Intravenously injected gold nanoparticles cross the blood–tumor barrier, but are largely blocked by the normal blood–brain barrier, enabling high-resolution computed tomography tumor imaging. Gold radiation enhancement significantly improved long-term survival compared with radiotherapy alone. This approach holds promise to improve therapy of human brain tumors and other cancers. PMID:23265347

High-throughput ultraviolet photoacoustic microscopy with multifocal excitation

NASA Astrophysics Data System (ADS)

Imai, Toru; Shi, Junhui; Wong, Terence T. W.; Li, Lei; Zhu, Liren; Wang, Lihong V.

2018-03-01

Ultraviolet photoacoustic microscopy (UV-PAM) is a promising intraoperative tool for surgical margin assessment (SMA), one that can provide label-free histology-like images with high resolution. In this study, using a microlens array and a one-dimensional (1-D) array ultrasonic transducer, we developed a high-throughput multifocal UV-PAM (MF-UV-PAM). Our new system achieved a 1.6 ± 0.2 μm lateral resolution and produced images 40 times faster than the previously developed point-by-point scanning UV-PAM. MF-UV-PAM provided a readily comprehensible photoacoustic image of a mouse brain slice with specific absorption contrast in ˜16 min, highlighting cell nuclei. Individual cell nuclei could be clearly resolved, showing its practical potential for intraoperative SMA.

Investigation of brain structure in the 1-month infant.

PubMed

Dean, Douglas C; Planalp, E M; Wooten, W; Schmidt, C K; Kecskemeti, S R; Frye, C; Schmidt, N L; Goldsmith, H H; Alexander, A L; Davidson, R J

2018-05-01

The developing brain undergoes systematic changes that occur at successive stages of maturation. Deviations from the typical neurodevelopmental trajectory are hypothesized to underlie many early childhood disorders; thus, characterizing the earliest patterns of normative brain development is essential. Recent neuroimaging research provides insight into brain structure during late childhood and adolescence; however, few studies have examined the infant brain, particularly in infants under 3 months of age. Using high-resolution structural MRI, we measured subcortical gray and white matter brain volumes in a cohort (N = 143) of 1-month infants and examined characteristics of these volumetric measures throughout this early period of neurodevelopment. We show that brain volumes undergo age-related changes during the first month of life, with the corresponding patterns of regional asymmetry and sexual dimorphism. Specifically, males have larger total brain volume and volumes differ by sex in regionally specific brain regions, after correcting for total brain volume. Consistent with findings from studies of later childhood and adolescence, subcortical regions appear more rightward asymmetric. Neither sex differences nor regional asymmetries changed with gestation-corrected age. Our results complement a growing body of work investigating the earliest neurobiological changes associated with development and suggest that asymmetry and sexual dimorphism are present at birth.

Grade classification of neuroepithelial tumors using high-resolution magic-angle spinning proton nuclear magnetic resonance spectroscopy and pattern recognition.

PubMed

Chen, WenXue; Lou, HaiYan; Zhang, HongPing; Nie, Xiu; Lan, WenXian; Yang, YongXia; Xiang, Yun; Qi, JianPin; Lei, Hao; Tang, HuiRu; Chen, FenEr; Deng, Feng

2011-07-01

Clinical data have shown that survival rates vary considerably among brain tumor patients, according to the type and grade of the tumor. Metabolite profiles of intact tumor tissues measured with high-resolution magic-angle spinning proton nuclear magnetic resonance spectroscopy (HRMAS (1)H NMRS) can provide important information on tumor biology and metabolism. These metabolic fingerprints can then be used for tumor classification and grading, with great potential value for tumor diagnosis. We studied the metabolic characteristics of 30 neuroepithelial tumor biopsies, including two astrocytomas (grade I), 12 astrocytomas (grade II), eight anaplastic astrocytomas (grade III), three glioblastomas (grade IV) and five medulloblastomas (grade IV) from 30 patients using HRMAS (1)H NMRS. The results were correlated with pathological features using multivariate data analysis, including principal component analysis (PCA). There were significant differences in the levels of N-acetyl-aspartate (NAA), creatine, myo-inositol, glycine and lactate between tumors of different grades (P<0.05). There were also significant differences in the ratios of NAA/creatine, lactate/creatine, myo-inositol/creatine, glycine/creatine, scyllo-inositol/creatine and alanine/creatine (P<0.05). A soft independent modeling of class analogy model produced a predictive accuracy of 87% for high-grade (grade III-IV) brain tumors with a sensitivity of 87% and a specificity of 93%. HRMAS (1)H NMR spectroscopy in conjunction with pattern recognition thus provides a potentially useful tool for the rapid and accurate classification of human brain tumor grades.

A PRESTO-SENSE sequence with alternating partial-Fourier encoding for rapid susceptibility-weighted 3D MRI time series.

PubMed

Klarhöfer, Markus; Dilharreguy, Bixente; van Gelderen, Peter; Moonen, Chrit T W

2003-10-01

A 3D sequence for dynamic susceptibility imaging is proposed which combines echo-shifting principles (such as PRESTO), sensitivity encoding (SENSE), and partial-Fourier acquisition. The method uses a moderate SENSE factor of 2 and takes advantage of an alternating partial k-space acquisition in the "slow" phase encode direction allowing an iterative reconstruction using high-resolution phase estimates. Offering an isotropic spatial resolution of 4 x 4 x 4 mm(3), the novel sequence covers the whole brain including parts of the cerebellum in 0.5 sec. Its temporal signal stability is comparable to that of a full-Fourier, full-FOV EPI sequence having the same dynamic scan time but much less brain coverage. Initial functional MRI experiments showed consistent activation in the motor cortex with an average signal change slightly less than that of EPI. Copyright 2003 Wiley-Liss, Inc.

Crystal structures of a GABAA-receptor chimera reveal new endogenous neurosteroid-binding sites.

PubMed

Laverty, Duncan; Thomas, Philip; Field, Martin; Andersen, Ole J; Gold, Matthew G; Biggin, Philip C; Gielen, Marc; Smart, Trevor G

2017-11-01

γ-Aminobutyric acid receptors (GABA A Rs) are vital for controlling excitability in the brain. This is emphasized by the numerous neuropsychiatric disorders that result from receptor dysfunction. A critical component of most native GABA A Rs is the α subunit. Its transmembrane domain is the target for many modulators, including endogenous brain neurosteroids that impact anxiety, stress and depression, and for therapeutic drugs, such as general anesthetics. Understanding the basis for the modulation of GABA A R function requires high-resolution structures. Here we present the first atomic structures of a GABA A R chimera at 2.8-Å resolution, including those bound with potentiating and inhibitory neurosteroids. These structures define new allosteric binding sites for these modulators that are associated with the α-subunit transmembrane domain. Our findings will enable the exploitation of neurosteroids for therapeutic drug design to regulate GABA A Rs in neurological disorders.

A Hough Transform Global Probabilistic Approach to Multiple-Subject Diffusion MRI Tractography

PubMed Central

Aganj, Iman; Lenglet, Christophe; Jahanshad, Neda; Yacoub, Essa; Harel, Noam; Thompson, Paul M.; Sapiro, Guillermo

2011-01-01

A global probabilistic fiber tracking approach based on the voting process provided by the Hough transform is introduced in this work. The proposed framework tests candidate 3D curves in the volume, assigning to each one a score computed from the diffusion images, and then selects the curves with the highest scores as the potential anatomical connections. The algorithm avoids local minima by performing an exhaustive search at the desired resolution. The technique is easily extended to multiple subjects, considering a single representative volume where the registered high-angular resolution diffusion images (HARDI) from all the subjects are non-linearly combined, thereby obtaining population-representative tracts. The tractography algorithm is run only once for the multiple subjects, and no tract alignment is necessary. We present experimental results on HARDI volumes, ranging from simulated and 1.5T physical phantoms to 7T and 4T human brain and 7T monkey brain datasets. PMID:21376655

Localization, correlation, and visualization of electroencephalographic surface electrodes and brain anatomy in epilepsy studies

NASA Astrophysics Data System (ADS)

Brinkmann, Benjamin H.; O'Brien, Terence J.; Robb, Richard A.; Sharbrough, Frank W.

1997-05-01

Advances in neuroimaging have enhanced the clinician's ability to localize the epileptogenic zone in focal epilepsy, but 20-50 percent of these cases still remain unlocalized. Many sophisticated modalities have been used to study epilepsy, but scalp electrode recorded electroencephalography is particularly useful due to its noninvasive nature and excellent temporal resolution. This study is aimed at specific locations of scalp electrode EEG information for correlation with anatomical structures in the brain. 3D position localizing devices commonly used in virtual reality systems are used to digitize the coordinates of scalp electrodes in a standard clinical configuration. The electrode coordinates are registered with a high- resolution MRI dataset using a robust surface matching algorithm. Volume rendering can then be used to visualize the electrodes and electrode potentials interpolated over the scalp. The accuracy of the coordinate registration is assessed quantitatively with a realistic head phantom.

Using quantum filters to process images of diffuse axonal injury

NASA Astrophysics Data System (ADS)

Pineda Osorio, Mateo

2014-06-01

Some images corresponding to a diffuse axonal injury (DAI) are processed using several quantum filters such as Hermite Weibull and Morse. Diffuse axonal injury is a particular, common and severe case of traumatic brain injury (TBI). DAI involves global damage on microscopic scale of brain tissue and causes serious neurologic abnormalities. New imaging techniques provide excellent images showing cellular damages related to DAI. Said images can be processed with quantum filters, which accomplish high resolutions of dendritic and axonal structures both in normal and pathological state. Using the Laplacian operators from the new quantum filters, excellent edge detectors for neurofiber resolution are obtained. Image quantum processing of DAI images is made using computer algebra, specifically Maple. Quantum filter plugins construction is proposed as a future research line, which can incorporated to the ImageJ software package, making its use simpler for medical personnel.

Multi-layer Cortical Ca2+ Imaging in Freely Moving Mice with Prism Probes and Miniaturized Fluorescence Microscopy

PubMed Central

Gulati, Srishti; Cao, Vania Y.; Otte, Stephani

2017-01-01

In vivo circuit and cellular level functional imaging is a critical tool for understanding the brain in action. High resolution imaging of mouse cortical neurons with two-photon microscopy has provided unique insights into cortical structure, function and plasticity. However, these studies are limited to head fixed animals, greatly reducing the behavioral complexity available for study. In this paper, we describe a procedure for performing chronic fluorescence microscopy with cellular-resolution across multiple cortical layers in freely behaving mice. We used an integrated miniaturized fluorescence microscope paired with an implanted prism probe to simultaneously visualize and record the calcium dynamics of hundreds of neurons across multiple layers of the somatosensory cortex as the mouse engaged in a novel object exploration task, over several days. This technique can be adapted to other brain regions in different animal species for other behavioral paradigms. PMID:28654056

Decoding multiple sound categories in the human temporal cortex using high resolution fMRI.

PubMed

Zhang, Fengqing; Wang, Ji-Ping; Kim, Jieun; Parrish, Todd; Wong, Patrick C M

2015-01-01

Perception of sound categories is an important aspect of auditory perception. The extent to which the brain's representation of sound categories is encoded in specialized subregions or distributed across the auditory cortex remains unclear. Recent studies using multivariate pattern analysis (MVPA) of brain activations have provided important insights into how the brain decodes perceptual information. In the large existing literature on brain decoding using MVPA methods, relatively few studies have been conducted on multi-class categorization in the auditory domain. Here, we investigated the representation and processing of auditory categories within the human temporal cortex using high resolution fMRI and MVPA methods. More importantly, we considered decoding multiple sound categories simultaneously through multi-class support vector machine-recursive feature elimination (MSVM-RFE) as our MVPA tool. Results show that for all classifications the model MSVM-RFE was able to learn the functional relation between the multiple sound categories and the corresponding evoked spatial patterns and classify the unlabeled sound-evoked patterns significantly above chance. This indicates the feasibility of decoding multiple sound categories not only within but across subjects. However, the across-subject variation affects classification performance more than the within-subject variation, as the across-subject analysis has significantly lower classification accuracies. Sound category-selective brain maps were identified based on multi-class classification and revealed distributed patterns of brain activity in the superior temporal gyrus and the middle temporal gyrus. This is in accordance with previous studies, indicating that information in the spatially distributed patterns may reflect a more abstract perceptual level of representation of sound categories. Further, we show that the across-subject classification performance can be significantly improved by averaging the fMRI images over items, because the irrelevant variations between different items of the same sound category are reduced and in turn the proportion of signals relevant to sound categorization increases.

The neurobiological role of the dorsolateral prefrontal cortex in recovery from trauma. Longitudinal brain imaging study among survivors of the South Korean subway disaster.

PubMed

Lyoo, In Kyoon; Kim, Jieun E; Yoon, Sujung J; Hwang, Jaeuk; Bae, Sujin; Kim, Dajung J

2011-07-01

A multiwave longitudinal neuroimaging study in a cohort of direct survivors of a South Korean subway disaster, most of whom recovered from posttraumatic stress disorder 5 years after trauma, provided a unique opportunity to investigate the brain correlates of recovery from a severe psychological trauma. To investigate region-specific brain mobilization during successful recovery from posttraumatic stress disorder by assessing cortical thickness multiple times from early after trauma to recovery, and to examine whether a brain-derived neurotrophic factor gene polymorphism was associated with this brain mobilization. Five-year follow-up case-control study conducted from 2003-2007. Seoul National University and Hospital. Thirty psychologically traumatized disaster survivors and 36 age- and sex-matched control group members recruited from the disaster registry and local community, respectively, who contributed 156 high-resolution brain magnetic resonance images during 3 waves of assessments. Cerebral cortical thickness measured in high-resolution anatomic magnetic resonance images using a validated cortical thickness analysis tool and its prospective changes from early after trauma to recovery in trauma-exposed individuals and controls. Trauma-exposed individuals had greater dorsolateral prefrontal cortical (DLPFC) thickness 1.42 years after trauma (right DLPFC, 5.4%; left superior frontal cortex, 5.8%; and left inferior frontal cortex, 5.3% [all clusters, P ≤ .01]) relative to controls. Thicknesses gradually normalized over time during recovery. We found a positive linear trend, with trauma-exposed individuals with a valine/valine genotype having the greatest DLPFC cortical thickness, followed by those with a methionine genotype and controls (P < .001 for trend). Greater DLPFC thickness was associated with greater posttraumatic stress disorder symptom reductions and better recovery. The DLPFC region might play an important role in psychological recovery from a severely traumatic event in humans.

SPECT-imaging of activity-dependent changes in regional cerebral blood flow induced by electrical and optogenetic self-stimulation in mice.

PubMed

Kolodziej, Angela; Lippert, Michael; Angenstein, Frank; Neubert, Jenni; Pethe, Annette; Grosser, Oliver S; Amthauer, Holger; Schroeder, Ulrich H; Reymann, Klaus G; Scheich, Henning; Ohl, Frank W; Goldschmidt, Jürgen

2014-12-01

Electrical and optogenetic methods for brain stimulation are widely used in rodents for manipulating behavior and analyzing functional connectivities in neuronal circuits. High-resolution in vivo imaging of the global, brain-wide, activation patterns induced by these stimulations has remained challenging, in particular in awake behaving mice. We here mapped brain activation patterns in awake, intracranially self-stimulating mice using a novel protocol for single-photon emission computed tomography (SPECT) imaging of regional cerebral blood flow (rCBF). Mice were implanted with either electrodes for electrical stimulation of the medial forebrain bundle (mfb-microstim) or with optical fibers for blue-light stimulation of channelrhodopsin-2 expressing neurons in the ventral tegmental area (vta-optostim). After training for self-stimulation by current or light application, respectively, mice were implanted with jugular vein catheters and intravenously injected with the flow tracer 99m-technetium hexamethylpropyleneamine oxime (99mTc-HMPAO) during seven to ten minutes of intracranial self-stimulation or ongoing behavior without stimulation. The 99mTc-brain distributions were mapped in anesthetized animals after stimulation using multipinhole SPECT. Upon self-stimulation rCBF strongly increased at the electrode tip in mfb-microstim mice. In vta-optostim mice peak activations were found outside the stimulation site. Partly overlapping brain-wide networks of activations and deactivations were found in both groups. When testing all self-stimulating mice against all controls highly significant activations were found in the rostromedial nucleus accumbens shell. SPECT-imaging of rCBF using intravenous tracer-injection during ongoing behavior is a new tool for imaging regional brain activation patterns in awake behaving rodents providing higher spatial and temporal resolutions than 18F-2-fluoro-2-dexoyglucose positron emission tomography. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

High-resolution, high-throughput imaging with a multibeam scanning electron microscope

PubMed Central

EBERLE, AL; MIKULA, S; SCHALEK, R; LICHTMAN, J; TATE, ML KNOTHE; ZEIDLER, D

2015-01-01

Electron–electron interactions and detector bandwidth limit the maximal imaging speed of single-beam scanning electron microscopes. We use multiple electron beams in a single column and detect secondary electrons in parallel to increase the imaging speed by close to two orders of magnitude and demonstrate imaging for a variety of samples ranging from biological brain tissue to semiconductor wafers. Lay Description The composition of our world and our bodies on the very small scale has always fascinated people, making them search for ways to make this visible to the human eye. Where light microscopes reach their resolution limit at a certain magnification, electron microscopes can go beyond. But their capability of visualizing extremely small features comes at the cost of a very small field of view. Some of the questions researchers seek to answer today deal with the ultrafine structure of brains, bones or computer chips. Capturing these objects with electron microscopes takes a lot of time – maybe even exceeding the time span of a human being – or new tools that do the job much faster. A new type of scanning electron microscope scans with 61 electron beams in parallel, acquiring 61 adjacent images of the sample at the same time a conventional scanning electron microscope captures one of these images. In principle, the multibeam scanning electron microscope’s field of view is 61 times larger and therefore coverage of the sample surface can be accomplished in less time. This enables researchers to think about large-scale projects, for example in the rather new field of connectomics. A very good introduction to imaging a brain at nanometre resolution can be found within course material from Harvard University on http://www.mcb80x.org/# as featured media entitled ‘connectomics’. PMID:25627873

Low resolution brain electromagnetic tomography in a realistic geometry head model: a simulation study

NASA Astrophysics Data System (ADS)

Ding, Lei; Lai, Yuan; He, Bin

2005-01-01

It is of importance to localize neural sources from scalp recorded EEG. Low resolution brain electromagnetic tomography (LORETA) has received considerable attention for localizing brain electrical sources. However, most such efforts have used spherical head models in representing the head volume conductor. Investigation of the performance of LORETA in a realistic geometry head model, as compared with the spherical model, will provide useful information guiding interpretation of data obtained by using the spherical head model. The performance of LORETA was evaluated by means of computer simulations. The boundary element method was used to solve the forward problem. A three-shell realistic geometry (RG) head model was constructed from MRI scans of a human subject. Dipole source configurations of a single dipole located at different regions of the brain with varying depth were used to assess the performance of LORETA in different regions of the brain. A three-sphere head model was also used to approximate the RG head model, and similar simulations performed, and results compared with the RG-LORETA with reference to the locations of the simulated sources. Multi-source localizations were discussed and examples given in the RG head model. Localization errors employing the spherical LORETA, with reference to the source locations within the realistic geometry head, were about 20-30 mm, for four brain regions evaluated: frontal, parietal, temporal and occipital regions. Localization errors employing the RG head model were about 10 mm over the same four brain regions. The present simulation results suggest that the use of the RG head model reduces the localization error of LORETA, and that the RG head model based LORETA is desirable if high localization accuracy is needed.

Effects of finite spatial resolution on quantitative CBF images from dynamic PET

DOE Office of Scientific and Technical Information (OSTI.GOV)

Phelps, M.E.; Huang, S.C.; Mahoney, D.K.

1985-05-01

The finite spatial resolution of PET causes the time-activity responses on pixels around the boundaries between gray and white matter regions to contain kinetic components from tissues of different CBF's. CBF values estimated from kinetics of such mixtures are underestimated because of the nonlinear relationship between the time-activity response and the estimated CBF. Computer simulation is used to investigate these effects on phantoms of circular structures and realistic brain slice in terms of object size and quantitative CBF values. The CBF image calculated is compared to the case of having resolution loss alone. Results show that the size of amore » high flow region in the CBF image is decreased while that of a low flow region is increased. For brain phantoms, the qualitative appearance of CBF images is not seriously affected, but the estimated CBF's are underestimated by 11 to 16 percent in local gray matter regions (of size 1 cm/sup 2/) with about 14 percent reduction in global CBF over the whole slice. It is concluded that the combined effect of finite spatial resolution and the nonlinearity in estimating CBF from dynamic PET is quite significant and must be considered in processing and interpreting quantitative CBF images.« less

The INIA19 Template and NeuroMaps Atlas for Primate Brain Image Parcellation and Spatial Normalization

PubMed Central

Rohlfing, Torsten; Kroenke, Christopher D.; Sullivan, Edith V.; Dubach, Mark F.; Bowden, Douglas M.; Grant, Kathleen A.; Pfefferbaum, Adolf

2012-01-01

The INIA19 is a new, high-quality template for imaging-based studies of non-human primate brains, created from high-resolution, T1-weighted magnetic resonance (MR) images of 19 rhesus macaque (Macaca mulatta) animals. Combined with the comprehensive cortical and sub-cortical label map of the NeuroMaps atlas, the INIA19 is equally suitable for studies requiring both spatial normalization and atlas label propagation. Population-averaged template images are provided for both the brain and the whole head, to allow alignment of the atlas with both skull-stripped and unstripped data, and thus to facilitate its use for skull stripping of new images. This article describes the construction of the template using freely available software tools, as well as the template itself, which is being made available to the scientific community (http://nitrc.org/projects/inia19/). PMID:23230398

Multiscale Imaging of the Mouse Cortex Using Two-Photon Microscopy and Wide-Field Illumination

NASA Astrophysics Data System (ADS)

Bumstead, Jonathan R.

The mouse brain can be studied over vast spatial scales ranging from microscopic imaging of single neurons to macroscopic measurements of hemodynamics acquired over the majority of the mouse cortex. However, most neuroimaging modalities are limited by a fundamental trade-off between the spatial resolution and the field-of-view (FOV) over which the brain can be imaged, making it difficult to fully understand the functional and structural architecture of the healthy mouse brain and its disruption in disease. My dissertation has focused on developing multiscale optical systems capable of imaging the mouse brain at both microscopic and mesoscopic spatial scales, specifically addressing the difference in spatial scales imaged with two-photon microscopy (TPM) and optical intrinsic signal imaging (OISI). Central to this work has been the formulation of a principled design strategy for extending the FOV of the two-photon microscope. Using this design approach, we constructed a TPM system with subcellular resolution and a FOV area 100 times greater than a conventional two-photon microscope. To image the ellipsoidal shape of the mouse cortex, we also developed the microscope to image arbitrary surfaces within a single frame using an electrically tunable lens. Finally, to address the speed limitations of the TPM systems developed during my dissertation, I also conducted research in large-scale neural phenomena occurring in the mouse brain imaged with high-speed OISI. The work conducted during my dissertation addresses some of the fundamental principles in designing and applying optical systems for multiscale imaging of the mouse brain.

Brain's tumor image processing using shearlet transform

NASA Astrophysics Data System (ADS)

Cadena, Luis; Espinosa, Nikolai; Cadena, Franklin; Korneeva, Anna; Kruglyakov, Alexey; Legalov, Alexander; Romanenko, Alexey; Zotin, Alexander

2017-09-01

Brain tumor detection is well known research area for medical and computer scientists. In last decades there has been much research done on tumor detection, segmentation, and classification. Medical imaging plays a central role in the diagnosis of brain tumors and nowadays uses methods non-invasive, high-resolution techniques, especially magnetic resonance imaging and computed tomography scans. Edge detection is a fundamental tool in image processing, particularly in the areas of feature detection and feature extraction, which aim at identifying points in a digital image at which the image has discontinuities. Shearlets is the most successful frameworks for the efficient representation of multidimensional data, capturing edges and other anisotropic features which frequently dominate multidimensional phenomena. The paper proposes an improved brain tumor detection method by automatically detecting tumor location in MR images, its features are extracted by new shearlet transform.

High spatial resolution compressed sensing (HSPARSE) functional MRI.

PubMed

Fang, Zhongnan; Van Le, Nguyen; Choy, ManKin; Lee, Jin Hyung

2016-08-01

To propose a novel compressed sensing (CS) high spatial resolution functional MRI (fMRI) method and demonstrate the advantages and limitations of using CS for high spatial resolution fMRI. A randomly undersampled variable density spiral trajectory enabling an acceleration factor of 5.3 was designed with a balanced steady state free precession sequence to achieve high spatial resolution data acquisition. A modified k-t SPARSE method was then implemented and applied with a strategy to optimize regularization parameters for consistent, high quality CS reconstruction. The proposed method improves spatial resolution by six-fold with 12 to 47% contrast-to-noise ratio (CNR), 33 to 117% F-value improvement and maintains the same temporal resolution. It also achieves high sensitivity of 69 to 99% compared the original ground-truth, small false positive rate of less than 0.05 and low hemodynamic response function distortion across a wide range of CNRs. The proposed method is robust to physiological noise and enables detection of layer-specific activities in vivo, which cannot be resolved using the highest spatial resolution Nyquist acquisition. The proposed method enables high spatial resolution fMRI that can resolve layer-specific brain activity and demonstrates the significant improvement that CS can bring to high spatial resolution fMRI. Magn Reson Med 76:440-455, 2016. © 2015 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. © 2015 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine.

Conflict monitoring and adjustment in the task-switching paradigm under different memory load conditions: an ERP/sLORETA analysis.

PubMed

Deng, Yuqin; Wang, Yan; Ding, Xiaoqian; Tang, Yi-Yuan

2015-02-11

The aim of the present study was to examine electrophysiological and behavioral changes caused by different memory loads in a task-switching paradigm. A total of 31 healthy individuals were subjected to a task, in which the stimulus-response reversal paradigm was combined with the task-switching paradigm. The event-related potentials were recorded and the N2 component, an index of conflict processing, was measured. In addition, the neural sources of N2 were further analyzed by standardized low-resolution brain electromagnetic tomography. The event-related potential results showed that high memory load triggered a higher N2 mean amplitude. Moreover, the standardized low-resolution brain electromagnetic tomography data showed that high memory load caused an increase in current densities at the anterior cingulate cortex and the prefrontal cortex in the task-switching paradigm. In summary, our findings provide electrophysiological evidence to interpret possible influences of memory loads on conflict monitoring and modulation during the task switching. These results imply that the working memory load overrules the influence of task-switching performance on the intensification of cognitive control.

Localized high-resolution DTI of the human midbrain using single-shot EPI, parallel imaging, and outer-volume suppression at 7 T

PubMed Central

Wargo, Christopher J.; Gore, John C.

2013-01-01

Localized high-resolution diffusion tensor images (DTI) from the midbrain were obtained using reduced field-of-view (rFOV) methods combined with SENSE parallel imaging and single-shot echo planar (EPI) acquisitions at 7 T. This combination aimed to diminish sensitivities of DTI to motion, susceptibility variations, and EPI artifacts at ultra-high field. Outer-volume suppression (OVS) was applied in DTI acquisitions at 2- and 1-mm2 resolutions, b=1000 s/mm2, and six diffusion directions, resulting in scans of 7- and 14-min durations. Mean apparent diffusion coefficient (ADC) and fractional anisotropy (FA) values were measured in various fiber tract locations at the two resolutions and compared. Geometric distortion and signal-to-noise ratio (SNR) were additionally measured and compared for reduced-FOV and full-FOV DTI scans. Up to an eight-fold data reduction was achieved using DTI-OVS with SENSE at 1 mm2, and geometric distortion was halved. The localization of fiber tracts was improved, enabling targeted FA and ADC measurements. Significant differences in diffusion properties were observed between resolutions for a number of regions suggesting that FA values are impacted by partial volume effects even at a 2-mm2 resolution. The combined SENSE DTI-OVS approach allows large reductions in DTI data acquisition and provides improved quality for high-resolution diffusion studies of the human brain. PMID:23541390

EEG analysis of the brain activity during the observation of commercial, political, or public service announcements.

PubMed

Vecchiato, Giovanni; Astolfi, Laura; Tabarrini, Alessandro; Salinari, Serenella; Mattia, Donatella; Cincotti, Febo; Bianchi, Luigi; Sorrentino, Domenica; Aloise, Fabio; Soranzo, Ramon; Babiloni, Fabio

2010-01-01

The use of modern brain imaging techniques could be useful to understand what brain areas are involved in the observation of video clips related to commercial advertising, as well as for the support of political campaigns, and also the areas of Public Service Announcements (PSAs). In this paper we describe the capability of tracking brain activity during the observation of commercials, political spots, and PSAs with advanced high-resolution EEG statistical techniques in time and frequency domains in a group of normal subjects. We analyzed the statistically significant cortical spectral power activity in different frequency bands during the observation of a commercial video clip related to the use of a beer in a group of 13 normal subjects. In addition, a TV speech of the Prime Minister of Italy was analyzed in two groups of swing and "supporter" voters. Results suggested that the cortical activity during the observation of commercial spots could vary consistently across the spot. This fact suggest the possibility to remove the parts of the spot that are not particularly attractive by using those cerebral indexes. The cortical activity during the observation of the political speech indicated a major cortical activity in the supporters group when compared to the swing voters. In this case, it is possible to conclude that the communication proposed has failed to raise attention or interest on swing voters. In conclusions, high-resolution EEG statistical techniques have been proved to able to generate useful insights about the particular fruition of TV messages, related to both commercial as well as political fields.

EEG Analysis of the Brain Activity during the Observation of Commercial, Political, or Public Service Announcements

PubMed Central

Vecchiato, Giovanni; Astolfi, Laura; Tabarrini, Alessandro; Salinari, Serenella; Mattia, Donatella; Cincotti, Febo; Bianchi, Luigi; Sorrentino, Domenica; Aloise, Fabio; Soranzo, Ramon; Babiloni, Fabio

2010-01-01

The use of modern brain imaging techniques could be useful to understand what brain areas are involved in the observation of video clips related to commercial advertising, as well as for the support of political campaigns, and also the areas of Public Service Announcements (PSAs). In this paper we describe the capability of tracking brain activity during the observation of commercials, political spots, and PSAs with advanced high-resolution EEG statistical techniques in time and frequency domains in a group of normal subjects. We analyzed the statistically significant cortical spectral power activity in different frequency bands during the observation of a commercial video clip related to the use of a beer in a group of 13 normal subjects. In addition, a TV speech of the Prime Minister of Italy was analyzed in two groups of swing and “supporter” voters. Results suggested that the cortical activity during the observation of commercial spots could vary consistently across the spot. This fact suggest the possibility to remove the parts of the spot that are not particularly attractive by using those cerebral indexes. The cortical activity during the observation of the political speech indicated a major cortical activity in the supporters group when compared to the swing voters. In this case, it is possible to conclude that the communication proposed has failed to raise attention or interest on swing voters. In conclusions, high-resolution EEG statistical techniques have been proved to able to generate useful insights about the particular fruition of TV messages, related to both commercial as well as political fields. PMID:20069055

Video-rate functional photoacoustic microscopy at depths

NASA Astrophysics Data System (ADS)

Wang, Lidai; Maslov, Konstantin; Xing, Wenxin; Garcia-Uribe, Alejandro; Wang, Lihong V.

2012-10-01

We report the development of functional photoacoustic microscopy capable of video-rate high-resolution in vivo imaging in deep tissue. A lightweight photoacoustic probe is made of a single-element broadband ultrasound transducer, a compact photoacoustic beam combiner, and a bright-field light delivery system. Focused broadband ultrasound detection provides a 44-μm lateral resolution and a 28-μm axial resolution based on the envelope (a 15-μm axial resolution based on the raw RF signal). Due to the efficient bright-field light delivery, the system can image as deep as 4.8 mm in vivo using low excitation pulse energy (28 μJ per pulse, 0.35 mJ/cm2 on the skin surface). The photoacoustic probe is mounted on a fast-scanning voice-coil scanner to acquire 40 two-dimensional (2-D) B-scan images per second over a 9-mm range. High-resolution anatomical imaging is demonstrated in the mouse ear and brain. Via fast dual-wavelength switching, oxygen dynamics of mouse cardio-vasculature is imaged in realtime as well.

Fully integrated reflection-mode photoacoustic, two-photon, and second harmonic generation microscopy in vivo

NASA Astrophysics Data System (ADS)

Song, Wei; Xu, Qiang; Zhang, Yang; Zhan, Yang; Zheng, Wei; Song, Liang

2016-08-01

The ability to obtain comprehensive structural and functional information from intact biological tissue in vivo is highly desirable for many important biomedical applications, including cancer and brain studies. Here, we developed a fully integrated multimodal microscopy that can provide photoacoustic (optical absorption), two-photon (fluorescence), and second harmonic generation (SHG) information from tissue in vivo, with intrinsically co-registered images. Moreover, using a delicately designed optical-acoustic coupling configuration, a high-frequency miniature ultrasonic transducer was integrated into a water-immersion optical objective, thus allowing all three imaging modalities to provide a high lateral resolution of ~290 nm with reflection-mode imaging capability, which is essential for studying intricate anatomy, such as that of the brain. Taking advantage of the complementary and comprehensive contrasts of the system, we demonstrated high-resolution imaging of various tissues in living mice, including microvasculature (by photoacoustics), epidermis cells, cortical neurons (by two-photon fluorescence), and extracellular collagen fibers (by SHG). The intrinsic image co-registration of the three modalities conveniently provided improved visualization and understanding of the tissue microarchitecture. The reported results suggest that, by revealing complementary tissue microstructures in vivo, this multimodal microscopy can potentially facilitate a broad range of biomedical studies, such as imaging of the tumor microenvironment and neurovascular coupling.

Feasibility of creating a high-resolution 3D diffusion tensor imaging based atlas of the human brainstem: A case study at 11.7T

PubMed Central

Aggarwal, Manisha; Zhang, Jiangyang; Pletnikova, Olga; Crain, Barbara; Troncoso, Juan; Mori, Susumu

2013-01-01

A three-dimensional stereotaxic atlas of the human brainstem based on high resolution ex vivo diffusion tensor imaging (DTI) is introduced. The atlas consists of high resolution (125–255 μm isotropic) three-dimensional DT images of the formalin-fixed brainstem acquired at 11.7T. The DTI data revealed microscopic neuroanatomical details, allowing three-dimensional visualization and reconstruction of fiber pathways including the decussation of the pyramidal tract fibers, and interdigitating fascicles of the corticospinal and transverse pontine fibers. Additionally, strong grey-white matter contrasts in the apparent diffusion coefficient (ADC) maps enabled precise delineation of grey matter nuclei in the brainstem, including the cranial nerve and the inferior olivary nuclei. Comparison with myelin-stained histology shows that at the level of resolution achieved in this study, the structural details resolved with DTI contrasts in the brainstem were comparable to anatomical delineation obtained with histological sectioning. Major neural structures delineated from DTI contrasts in the brainstem are segmented and three-dimensionally reconstructed. Further, the ex vivo DTI data are nonlinearly mapped to a widely-used in vivo human brain atlas, to construct a high-resolution atlas of the brainstem in the Montreal Neurological Institute (MNI) stereotaxic coordinate space. The results demonstrate the feasibility of developing a 3D DTI based atlas for detailed characterization of brainstem neuroanatomy with high resolution and contrasts, which will be a useful resource for research and clinical applications. PMID:23384518

Chemical exchange saturation transfer MRI contrast in the human brain at 9.4 T.

PubMed

Zaiss, Moritz; Schuppert, Mark; Deshmane, Anagha; Herz, Kai; Ehses, Philipp; Füllbier, Lars; Lindig, Tobias; Bender, Benjamin; Ernemann, Ulrike; Scheffler, Klaus

2018-06-15

The high chemical shift separation at 9.4 T allows for selective saturation of proton pools in exchange with water protons. For the first time, highly selective and comprehensive chemical exchange saturation transfer (CEST) experiments were performed in the human brain at 9.4 T. This work provides insight into CEST signals in the human brain in comparison with existing animal studies, as well as with CEST effects in vivo at lower field strengths. A novel snapshot-CEST method for human brain scans at 9.4 T was optimized and employed for highly-spectrally-resolved (95 offsets) CEST measurements in healthy subjects and one brain tumor patient. Reproducibility and stability between scans was verified in grey and white matter after B 0 , B 1 , and motion correction of the acquired 3D CEST volumes. Two-step Lorentzian fitting was used to further improve separation of spectrally discernible signals to create known and novel CEST contrast maps at 9.4 T. At a saturation power of B 1  = 0.5 μT most selective CEST effects could be obtained in the human brain with high inter-scan reproducibility. While contrast behavior of previously measured signals at lower field, namely amide-, guanidyl- and NOE-CEST effects, could be reproduced, novel signals at 2.7 ppm, and -1.6 ppm could be verified in healthy subjects and in a brain tumor patient for the first time. High spectral resolution chemical exchange saturation transfer at 9.4 T allows deeper insights into the Z-spectrum structure of the human brain, and provides many different contrasts showing different correlations in healthy tissue and in tumor-affected areas of the brain, generating hypotheses for future investigations of in-vivo-CEST at UHF. Copyright © 2018 Elsevier Inc. All rights reserved.

A versatile new technique to clear mouse and human brain

NASA Astrophysics Data System (ADS)

Costantini, Irene; Di Giovanna, Antonino Paolo; Allegra Mascaro, Anna Letizia; Silvestri, Ludovico; Müllenbroich, Marie Caroline; Sacconi, Leonardo; Pavone, Francesco S.

2015-07-01

Large volumes imaging with microscopic resolution is limited by light scattering. In the last few years based on refractive index matching, different clearing approaches have been developed. Organic solvents and water-based optical clearing agents have been used for optical clearing of entire mouse brain. Although these methods guarantee high transparency and preservation of the fluorescence, though present other non-negligible limitations. Tissue transformation by CLARITY allows high transparency, whole brain immunolabelling and structural and molecular preservation. This method however requires a highly expensive refractive index matching solution limiting practical applicability. In this work we investigate the effectiveness of a water-soluble clearing agent, the 2,2'-thiodiethanol (TDE) to clear mouse and human brain. TDE does not quench the fluorescence signal, is compatible with immunostaining and does not introduce any deformation at sub-cellular level. The not viscous nature of the TDE make it a suitable agent to perform brain slicing during serial two-photon (STP) tomography. In fact, by improving penetration depth it reduces tissue slicing, decreasing the acquisition time and cutting artefacts. TDE can also be used as a refractive index medium for CLARITY. The potential of this method has been explored by imaging a whole transgenic mouse brain with the light sheet microscope. Moreover we apply this technique also on blocks of dysplastic human brain tissue transformed with CLARITY and labeled with different antibody. This clearing approach significantly expands the application of single and two-photon imaging, providing a new useful method for quantitative morphological analysis of structure in mouse and human brain.

High-resolution maps of real and illusory tactile activation in primary somatosensory cortex in individual monkeys with functional magnetic resonance imaging and optical imaging.

PubMed

Chen, Li M; Turner, Gregory H; Friedman, Robert M; Zhang, Na; Gore, John C; Roe, Anna W; Avison, Malcolm J

2007-08-22

Although blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) has been widely used to explore human brain function, questions remain regarding the ultimate spatial resolution of positive BOLD fMRI, and indeed the extent to which functional maps revealed by positive BOLD correlate spatially with maps obtained with other high-spatial-resolution mapping techniques commonly used in animals, such as optical imaging of intrinsic signal (OIS) and single-unit electrophysiology. Here, we demonstrate that the positive BOLD signal at 9.4T can reveal the fine topography of individual fingerpads in single-condition activation maps in nonhuman primates. These digit maps are similar to maps obtained from the same animal using intrinsic optical imaging. Furthermore, BOLD fMRI reliably resolved submillimeter spatial shifts in activation in area 3b previously identified with OIS (Chen et al., 2003) as neural correlates of the "funneling illusion." These data demonstrate that at high field, high-spatial-resolution topographic maps can be achieved using the positive BOLD signal, weakening previous notions regarding the spatial specificity of the positive BOLD signal.

Ventricular enlargement in schizophrenia related to volume reduction of the thalamus, striatum, and superior temporal cortex.

PubMed

Gaser, Christian; Nenadic, Igor; Buchsbaum, Bradley R; Hazlett, Erin A; Buchsbaum, Monte S

2004-01-01

Enlargement of the lateral ventricles is among the most frequently reported macroscopic brain structural changes in schizophrenia, although variable in extent and localization. The authors investigated whether ventricular enlargement is related to regionally specific volume loss. High-resolution magnetic resonance imaging scans from 39 patients with schizophrenia were analyzed with deformation-based morphometry, a voxel-wise whole brain morphometric technique. Significant negative correlations with the ventricle-brain ratio were found for voxels in the left and right thalamus and posterior putamen and in the left superior temporal gyrus and insula. Thalamic shrinkage, especially of medial nuclei and the adjacent striatum and insular cortex, appear to be important contributors to ventricular enlargement in schizophrenia.

Mouse brain magnetic resonance microscopy: Applications in Alzheimer disease.

PubMed

Lin, Lan; Fu, Zhenrong; Xu, Xiaoting; Wu, Shuicai

2015-05-01

Over the past two decades, various Alzheimer's disease (AD) trangenetic mice models harboring genes with mutation known to cause familial AD have been created. Today, high-resolution magnetic resonance microscopy (MRM) technology is being widely used in the study of AD mouse models. It has greatly facilitated and advanced our knowledge of AD. In this review, most of the attention is paid to fundamental of MRM, the construction of standard mouse MRM brain template and atlas, the detection of amyloid plaques, following up on brain atrophy and the future applications of MRM in transgenic AD mice. It is believed that future testing of potential drugs in mouse models with MRM will greatly improve the predictability of drug effect in preclinical trials. © 2015 Wiley Periodicals, Inc.

MRI-guided brain PET image filtering and partial volume correction

NASA Astrophysics Data System (ADS)

Yan, Jianhua; Chu-Shern Lim, Jason; Townsend, David W.

2015-02-01

Positron emission tomography (PET) image quantification is a challenging problem due to limited spatial resolution of acquired data and the resulting partial volume effects (PVE), which depend on the size of the structure studied in relation to the spatial resolution and which may lead to over or underestimation of the true tissue tracer concentration. In addition, it is usually necessary to perform image smoothing either during image reconstruction or afterwards to achieve a reasonable signal-to-noise ratio. Typically, an isotropic Gaussian filtering (GF) is used for this purpose. However, the noise suppression is at the cost of deteriorating spatial resolution. As hybrid imaging devices such as PET/MRI have become available, the complementary information derived from high definition morphologic images could be used to improve the quality of PET images. In this study, first of all, we propose an MRI-guided PET filtering method by adapting a recently proposed local linear model and then incorporate PVE into the model to get a new partial volume correction (PVC) method without parcellation of MRI. In addition, both the new filtering and PVC are voxel-wise non-iterative methods. The performance of the proposed methods were investigated with simulated dynamic FDG brain dataset and 18F-FDG brain data of a cervical cancer patient acquired with a simultaneous hybrid PET/MR scanner. The initial simulation results demonstrated that MRI-guided PET image filtering can produce less noisy images than traditional GF and bias and coefficient of variation can be further reduced by MRI-guided PET PVC. Moreover, structures can be much better delineated in MRI-guided PET PVC for real brain data.

Temporal and spatial neural dynamics in the perception of basic emotions from complex scenes

PubMed Central

Costa, Tommaso; Cauda, Franco; Crini, Manuella; Tatu, Mona-Karina; Celeghin, Alessia; de Gelder, Beatrice

2014-01-01

The different temporal dynamics of emotions are critical to understand their evolutionary role in the regulation of interactions with the surrounding environment. Here, we investigated the temporal dynamics underlying the perception of four basic emotions from complex scenes varying in valence and arousal (fear, disgust, happiness and sadness) with the millisecond time resolution of Electroencephalography (EEG). Event-related potentials were computed and each emotion showed a specific temporal profile, as revealed by distinct time segments of significant differences from the neutral scenes. Fear perception elicited significant activity at the earliest time segments, followed by disgust, happiness and sadness. Moreover, fear, disgust and happiness were characterized by two time segments of significant activity, whereas sadness showed only one long-latency time segment of activity. Multidimensional scaling was used to assess the correspondence between neural temporal dynamics and the subjective experience elicited by the four emotions in a subsequent behavioral task. We found a high coherence between these two classes of data, indicating that psychological categories defining emotions have a close correspondence at the brain level in terms of neural temporal dynamics. Finally, we localized the brain regions of time-dependent activity for each emotion and time segment with the low-resolution brain electromagnetic tomography. Fear and disgust showed widely distributed activations, predominantly in the right hemisphere. Happiness activated a number of areas mostly in the left hemisphere, whereas sadness showed a limited number of active areas at late latency. The present findings indicate that the neural signature of basic emotions can emerge as the byproduct of dynamic spatiotemporal brain networks as investigated with millisecond-range resolution, rather than in time-independent areas involved uniquely in the processing one specific emotion. PMID:24214921

Collimator design for a multipinhole brain SPECT insert for MRI

DOE Office of Scientific and Technical Information (OSTI.GOV)

Van Audenhaege, Karen; Van Holen, Roel; Vanhove, Christian

Purpose: Brain single photon emission computed tomography (SPECT) imaging is an important clinical tool, with unique tracers for studying neurological diseases. Nowadays, most commercial SPECT systems are combined with x-ray computed tomography (CT) in so-called SPECT/CT systems to obtain an anatomical background for the functional information. However, while CT images have a high spatial resolution, they have a low soft-tissue contrast, which is an important disadvantage for brain imaging. Magnetic resonance imaging (MRI), on the other hand, has a very high soft-tissue contrast and does not involve extra ionizing radiation. Therefore, the authors designed a brain SPECT insert that canmore » operate inside a clinical MRI. Methods: The authors designed and simulated a compact stationary multipinhole SPECT insert based on digital silicon photomultiplier detector modules, which have shown to be MR-compatible and have an excellent intrinsic resolution (0.5 mm) when combined with a monolithic 2 mm thick LYSO crystal. First, the authors optimized the different parameters of the SPECT system to maximize sensitivity for a given target resolution of 7.2 mm in the center of the field-of-view, given the spatial constraints of the MR system. Second, the authors performed noiseless simulations of two multipinhole configurations to evaluate sampling and reconstructed resolution. Finally, the authors performed Monte Carlo simulations and compared the SPECT insert with a clinical system with ultrahigh-resolution (UHR) fan beam collimators, based on contrast-to-noise ratio and a visual comparison of a Hoffman phantom with a 9 mm cold lesion. Results: The optimization resulted in a stationary multipinhole system with a collimator radius of 150.2 mm and a detector radius of 172.67 mm, which corresponds to four rings of 34 diSPM detector modules. This allows the authors to include eight rings of 24 pinholes, which results in a system volume sensitivity of 395 cps/MBq. Noiseless simulations show sufficient axial sampling (in a Defrise phantom) and a reconstructed resolution of 5.0 mm (in a cold-rod phantom). The authors compared the 24-pinhole setup with a 34-pinhole system (with the same detector radius but a collimator radius of 156.63 mm) and found that 34 pinholes result in better uniformity but a worse reconstruction of the cold-rod phantom. The authors also compared the 24-pinhole system with a clinical triple-head UHR fan beam system based on contrast-to-noise ratio and found that the 24-pinhole setup performs better for the 6 mm hot and the 16 mm cold lesions and worse for the 8 and 10 mm hot lesions. Finally, the authors reconstructed noisy projection data of a Hoffman phantom with a 9 mm cold lesion and found that the lesion was slightly better visible on the multipinhole image compared to the fan beam image. Conclusions: The authors have optimized a stationary multipinhole SPECT insert for MRI and showed the feasibility of doing brain SPECT imaging inside a MRI with an image quality similar to the best clinical SPECT systems available.« less

Optical microangiography enabling visualization of change in meninges after traumatic brain injury in mice in vivo

NASA Astrophysics Data System (ADS)

Choi, Woo June; Qin, Wan; Qi, Xiaoli; Wang, Ruikang K.

2016-03-01

Traumatic brain injury (TBI) is a form of brain injury caused by sudden impact on brain by an external mechanical force. Following the damage caused at the moment of injury, TBI influences pathophysiology in the brain that takes place within the minutes or hours involving alterations in the brain tissue morphology, cerebral blood flow (CBF), and pressure within skull, which become important contributors to morbidity after TBI. While many studies for the TBI pathophysiology have been investigated with brain cortex, the effect of trauma on intracranial tissues has been poorly studied. Here, we report use of high-resolution optical microangiography (OMAG) to monitor the changes in cranial meninges beneath the skull of mouse after TBI. TBI is induced on a brain of anesthetized mouse by thinning the skull using a soft drill where a series of drilling exert mechanical stress on the brain through the skull, resulting in mild brain injury. Intracranial OMAG imaging of the injured mouse brain during post-TBI phase shows interesting pathophysiological findings in the meningeal layers such as widening of subdural space as well as vasodilation of subarachnoid vessels. These processes are acute and reversible within hours. The results indicate potential of OMAG to explore mechanism involved following TBI on small animals in vivo.

Whole-organ atlas imaged by label-free high-resolution photoacoustic microscopy assisted by a microtome

NASA Astrophysics Data System (ADS)

Wong, Terence T. W.; Zhang, Ruiying; Hsu, Hsun-Chia; Maslov, Konstantin I.; Shi, Junhui; Chen, Ruimin; Shung, K. Kirk; Zhou, Qifa; Wang, Lihong V.

2018-02-01

In biomedical imaging, all optical techniques face a fundamental trade-off between spatial resolution and tissue penetration. Therefore, obtaining an organelle-level resolution image of a whole organ has remained a challenging and yet appealing scientific pursuit. Over the past decade, optical microscopy assisted by mechanical sectioning or chemical clearing of tissue has been demonstrated as a powerful technique to overcome this dilemma, one of particular use in imaging the neural network. However, this type of techniques needs lengthy special preparation of the tissue specimen, which hinders broad application in life sciences. Here, we propose a new label-free three-dimensional imaging technique, named microtomy-assisted photoacoustic microscopy (mPAM), for potentially imaging all biomolecules with 100% endogenous natural staining in whole organs with high fidelity. We demonstrate the first label-free mPAM, using UV light for label-free histology-like imaging, in whole organs (e.g., mouse brains), most of them formalin-fixed and paraffin- or agarose-embedded for minimal morphological deformation. Furthermore, mPAM with dual wavelength illuminations is also employed to image a mouse brain slice, demonstrating the potential for imaging of multiple biomolecules without staining. With visible light illumination, mPAM also shows its deep tissue imaging capability, which enables less slicing and hence reduces sectioning artifacts. mPAM could potentially provide a new insight for understanding complex biological organs.

Correlated components of ongoing EEG point to emotionally laden attention - a possible marker of engagement?

PubMed

Dmochowski, Jacek P; Sajda, Paul; Dias, Joao; Parra, Lucas C

2012-01-01

Recent evidence from functional magnetic resonance imaging suggests that cortical hemodynamic responses coincide in different subjects experiencing a common naturalistic stimulus. Here we utilize neural responses in the electroencephalogram (EEG) evoked by multiple presentations of short film clips to index brain states marked by high levels of correlation within and across subjects. We formulate a novel signal decomposition method which extracts maximally correlated signal components from multiple EEG records. The resulting components capture correlations down to a one-second time resolution, thus revealing that peak correlations of neural activity across viewings can occur in remarkable correspondence with arousing moments of the film. Moreover, a significant reduction in neural correlation occurs upon a second viewing of the film or when the narrative is disrupted by presenting its scenes scrambled in time. We also probe oscillatory brain activity during periods of heightened correlation, and observe during such times a significant increase in the theta band for a frontal component and reductions in the alpha and beta frequency bands for parietal and occipital components. Low-resolution EEG tomography of these components suggests that the correlated neural activity is consistent with sources in the cingulate and orbitofrontal cortices. Put together, these results suggest that the observed synchrony reflects attention- and emotion-modulated cortical processing which may be decoded with high temporal resolution by extracting maximally correlated components of neural activity.

Correlated Components of Ongoing EEG Point to Emotionally Laden Attention – A Possible Marker of Engagement?

PubMed Central

Dmochowski, Jacek P.; Sajda, Paul; Dias, Joao; Parra, Lucas C.

2012-01-01

Recent evidence from functional magnetic resonance imaging suggests that cortical hemodynamic responses coincide in different subjects experiencing a common naturalistic stimulus. Here we utilize neural responses in the electroencephalogram (EEG) evoked by multiple presentations of short film clips to index brain states marked by high levels of correlation within and across subjects. We formulate a novel signal decomposition method which extracts maximally correlated signal components from multiple EEG records. The resulting components capture correlations down to a one-second time resolution, thus revealing that peak correlations of neural activity across viewings can occur in remarkable correspondence with arousing moments of the film. Moreover, a significant reduction in neural correlation occurs upon a second viewing of the film or when the narrative is disrupted by presenting its scenes scrambled in time. We also probe oscillatory brain activity during periods of heightened correlation, and observe during such times a significant increase in the theta band for a frontal component and reductions in the alpha and beta frequency bands for parietal and occipital components. Low-resolution EEG tomography of these components suggests that the correlated neural activity is consistent with sources in the cingulate and orbitofrontal cortices. Put together, these results suggest that the observed synchrony reflects attention- and emotion-modulated cortical processing which may be decoded with high temporal resolution by extracting maximally correlated components of neural activity. PMID:22623915

An anatomically comprehensive atlas of the adult human brain transcriptome

PubMed Central

Guillozet-Bongaarts, Angela L.; Shen, Elaine H.; Ng, Lydia; Miller, Jeremy A.; van de Lagemaat, Louie N.; Smith, Kimberly A.; Ebbert, Amanda; Riley, Zackery L.; Abajian, Chris; Beckmann, Christian F.; Bernard, Amy; Bertagnolli, Darren; Boe, Andrew F.; Cartagena, Preston M.; Chakravarty, M. Mallar; Chapin, Mike; Chong, Jimmy; Dalley, Rachel A.; David Daly, Barry; Dang, Chinh; Datta, Suvro; Dee, Nick; Dolbeare, Tim A.; Faber, Vance; Feng, David; Fowler, David R.; Goldy, Jeff; Gregor, Benjamin W.; Haradon, Zeb; Haynor, David R.; Hohmann, John G.; Horvath, Steve; Howard, Robert E.; Jeromin, Andreas; Jochim, Jayson M.; Kinnunen, Marty; Lau, Christopher; Lazarz, Evan T.; Lee, Changkyu; Lemon, Tracy A.; Li, Ling; Li, Yang; Morris, John A.; Overly, Caroline C.; Parker, Patrick D.; Parry, Sheana E.; Reding, Melissa; Royall, Joshua J.; Schulkin, Jay; Sequeira, Pedro Adolfo; Slaughterbeck, Clifford R.; Smith, Simon C.; Sodt, Andy J.; Sunkin, Susan M.; Swanson, Beryl E.; Vawter, Marquis P.; Williams, Derric; Wohnoutka, Paul; Zielke, H. Ronald; Geschwind, Daniel H.; Hof, Patrick R.; Smith, Stephen M.; Koch, Christof; Grant, Seth G. N.; Jones, Allan R.

2014-01-01

Neuroanatomically precise, genome-wide maps of transcript distributions are critical resources to complement genomic sequence data and to correlate functional and genetic brain architecture. Here we describe the generation and analysis of a transcriptional atlas of the adult human brain, comprising extensive histological analysis and comprehensive microarray profiling of ~900 neuroanatomically precise subdivisions in two individuals. Transcriptional regulation varies enormously by anatomical location, with different regions and their constituent cell types displaying robust molecular signatures that are highly conserved between individuals. Analysis of differential gene expression and gene co-expression relationships demonstrates that brain-wide variation strongly reflects the distributions of major cell classes such as neurons, oligodendrocytes, astrocytes and microglia. Local neighbourhood relationships between fine anatomical subdivisions are associated with discrete neuronal subtypes and genes involved with synaptic transmission. The neocortex displays a relatively homogeneous transcriptional pattern, but with distinct features associated selectively with primary sensorimotor cortices and with enriched frontal lobe expression. Notably, the spatial topography of the neocortex is strongly reflected in its molecular topography— the closer two cortical regions, the more similar their transcriptomes. This freely accessible online data resource forms a high-resolution transcriptional baseline for neurogenetic studies of normal and abnormal human brain function. PMID:22996553

Optogenetic Functional MRI

PubMed Central

Lin, Peter; Fang, Zhongnan; Liu, Jia; Lee, Jin Hyung

2016-01-01

The investigation of the functional connectivity of precise neural circuits across the entire intact brain can be achieved through optogenetic functional magnetic resonance imaging (ofMRI), which is a novel technique that combines the relatively high spatial resolution of high-field fMRI with the precision of optogenetic stimulation. Fiber optics that enable delivery of specific wavelengths of light deep into the brain in vivo are implanted into regions of interest in order to specifically stimulate targeted cell types that have been genetically induced to express light-sensitive trans-membrane conductance channels, called opsins. fMRI is used to provide a non-invasive method of determining the brain's global dynamic response to optogenetic stimulation of specific neural circuits through measurement of the blood-oxygen-level-dependent (BOLD) signal, which provides an indirect measurement of neuronal activity. This protocol describes the construction of fiber optic implants, the implantation surgeries, the imaging with photostimulation and the data analysis required to successfully perform ofMRI. In summary, the precise stimulation and whole-brain monitoring ability of ofMRI are crucial factors in making ofMRI a powerful tool for the study of the connectomics of the brain in both healthy and diseased states. PMID:27167840

Analysis of acute brain slices by electron microscopy: a correlative light-electron microscopy workflow based on Tokuyasu cryo-sectioning.

PubMed

Loussert Fonta, Celine; Leis, Andrew; Mathisen, Cliff; Bouvier, David S; Blanchard, Willy; Volterra, Andrea; Lich, Ben; Humbel, Bruno M

2015-01-01

Acute brain slices are slices of brain tissue that are kept vital in vitro for further recordings and analyses. This tool is of major importance in neurobiology and allows the study of brain cells such as microglia, astrocytes, neurons and their inter/intracellular communications via ion channels or transporters. In combination with light/fluorescence microscopies, acute brain slices enable the ex vivo analysis of specific cells or groups of cells inside the slice, e.g. astrocytes. To bridge ex vivo knowledge of a cell with its ultrastructure, we developed a correlative microscopy approach for acute brain slices. The workflow begins with sampling of the tissue and precise trimming of a region of interest, which contains GFP-tagged astrocytes that can be visualised by fluorescence microscopy of ultrathin sections. The astrocytes and their surroundings are then analysed by high resolution scanning transmission electron microscopy (STEM). An important aspect of this workflow is the modification of a commercial cryo-ultramicrotome to observe the fluorescent GFP signal during the trimming process. It ensured that sections contained at least one GFP astrocyte. After cryo-sectioning, a map of the GFP-expressing astrocytes is established and transferred to correlation software installed on a focused ion beam scanning electron microscope equipped with a STEM detector. Next, the areas displaying fluorescence are selected for high resolution STEM imaging. An overview area (e.g. a whole mesh of the grid) is imaged with an automated tiling and stitching process. In the final stitched image, the local organisation of the brain tissue can be surveyed or areas of interest can be magnified to observe fine details, e.g. vesicles or gold labels on specific proteins. The robustness of this workflow is contingent on the quality of sample preparation, based on Tokuyasu's protocol. This method results in a reasonable compromise between preservation of morphology and maintenance of antigenicity. Finally, an important feature of this approach is that the fluorescence of the GFP signal is preserved throughout the entire preparation process until the last step before electron microscopy. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Brain structural changes following adaptive cognitive training assessed by Tensor-Based Morphometry (TBM)

PubMed Central

Colom, Roberto; Hua, Xue; Martínez, Kenia; Burgaleta, Miguel; Román, Francisco J.; Gunter, Jeffrey L.; Carmona, Susanna; Jaeggi, Susanne M.; Thompson, Paul M.

2016-01-01

Tensor-Based Morphometry (TBM) allows the automatic mapping of brain changes across time building 3D deformation maps. This technique has been applied for tracking brain degeneration in Alzheimer's and other neurodegenerative diseases with high sensitivity and reliability. Here we applied TBM to quantify changes in brain structure after completing a challenging adaptive cognitive training program based on the n-back task. Twenty-six young women completed twenty-four training sessions across twelve weeks and they showed, on average, large cognitive improvements. High-resolution MRI scans were obtained before and after training. The computed longitudinal deformation maps were analyzed for answering three questions: (a) Are there differential brain structural changes in the training group as compared with a matched control group? (b) Are these changes related to performance differences in the training program? (c) Are standardized changes in a set of psychological factors (fluid and crystallized intelligence, working memory, and attention control) measured before and after training, related to structural changes in the brain? Results showed (a) greater structural changes for the training group in the temporal lobe, (b) a negative correlation between these changes and performance across training sessions (the greater the structural change, the lower the cognitive performance improvements), and (c) negligible effects regarding the psychological factors measured before and after training. PMID:27477628

Estimation of position resolution for DOI-PET detector using diameter 0.2 mm WLS fibers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kaneko, Naomi; Ito, Hiroshi; Kawai, Hideyuki

We have been developing sub mm resolution andmore » $$ 1 million DOI-PET detector using wavelength shifting fibers (WLSF), scintillation crystals of plate shape and SiPM (MPPC: HAMAMATSU K. K.). Conventional design of DOI-PET detector is obtained about mm{sup 3} of resolution by using some blocks detecting gamma-ray in mm 3 voxel. It requires the production cost of $$ a few ten million or more for high technique of processing crystal and a lot of number of photo-devices, and this technology is reaching the limit of the resolution. Both higher resolution and lower cost of DOI-PET detector production is challenging for PET diagnosis population. We propose two type of detector. One is a whole body PET system, and the other for brain or small animal. Both PET system consist 6 blocks. the former consist of 6 layers 300 mm x 300 mm x 4 mm crystal plate. The latter consist 16 crystal layers, 4 x 4 crystal array. The size of crystal plate is 40 mm x 40 mm x 1 mm.The WLSF sheets connect to upper and lower plane. The whole PET systems connect 8 SiPMs are bonded on each side. For the brain PET, 9 WLSF fibers are bond on the each side. The expected position resolution maybe less than 1 mm at the former. We have estimation experimental performance the system using {sup 22}Na radioactive source. The collection efficiency of WLSF (R-3) sheet was achieved 10% with GAGG at 511 keV. The relation between reconstruction position and incident position is obtained linearity and achieved the resolution of 0.7 mm FWHM for x-axis of DOI by readout WLSF. (authors)« less

Transcranial functional ultrasound imaging of the brain using microbubble-enhanced ultrasensitive Doppler

PubMed Central

Errico, Claudia; Osmanski, Bruno-Félix; Pezet, Sophie; Couture, Olivier; Lenkei, Zsolt; Tanter, Mickael

2016-01-01

Functional ultrasound (fUS) is a novel neuroimaging technique, based on high-sensitivity ultrafast Doppler imaging of cerebral blood volume, capable of measuring brain activation and connectivity in rodents with high spatiotemporal resolution (100 μm, 1 ms). However, the skull attenuates acoustic waves, so fUS in rats currently requires craniotomy or a thinned-skull window. Here we propose a non-invasive approach by enhancing the fUS signal with a contrast agent, inert gas microbubbles. Plane-wave illumination of the brain at high frame rate (500 Hz compounded sequence with three tilted plane waves, PRF = 1500Hz with a 128 element 15 MHz linear transducer), yields highly-resolved neurovascular maps. We compared fUS imaging performance through the intact skull bone (transcranial fUS) versus a thinned-skull window in the same animal. First, we show that the vascular network of the adult rat brain can be imaged transcranially only after a bolus intravenous injection of microbubbles, which leads to a 9 dB gain in the contrast-to-tissue ratio. Next, we demonstrate that functional increase in the blood volume of the primary sensory cortex after targeted electrical-evoked stimulations of the sciatic nerve is observable transcranially in presence of contrast agents, with high reproducibility (Pearson's coefficient ρ = 0.7 ± 0.1, p = 0.85). Our work demonstrates that the combination of ultrafast Doppler imaging and injection of contrast agent allows non-invasive functional brain imaging through the intact skull bone in rats. These results should ease non-invasive longitudinal studies in rodents and open a promising perspective for the adoption of highly resolved fUS approaches for the adult human brain. PMID:26416649

Abnormal cerebrospinal fluid protein indices in schizophrenia.

PubMed

Kirch, D G; Kaufmann, C A; Papadopoulos, N M; Martin, B; Weinberger, D R

1985-10-01

Determinations of albumin and immunoglobulin G (IgG) were performed in paired cerebrospinal fluid (CSF) and serum samples from 24 subjects with schizophrenia. These determinations allowed calculation of two indices, one that is an indicator of integrity of the blood-brain barrier and the other a measure of selective IgG production within the central nervous system (CNS). In comparison with previously determined reference values, 7 of 24 (29%) subjects showed increased blood-brain barrier permeability, and 8 of 24 (33%) demonstrated elevated endogenous CNS IgG production. One of these eight also demonstrated oligoclonal banding on high-resolution protein electrophoresis of the CSF.

Imaging fast electrical activity in the brain with electrical impedance tomography

PubMed Central

Aristovich, Kirill Y.; Packham, Brett C.; Koo, Hwan; Santos, Gustavo Sato dos; McEvoy, Andy; Holder, David S.

2016-01-01

Imaging of neuronal depolarization in the brain is a major goal in neuroscience, but no technique currently exists that could image neural activity over milliseconds throughout the whole brain. Electrical impedance tomography (EIT) is an emerging medical imaging technique which can produce tomographic images of impedance changes with non-invasive surface electrodes. We report EIT imaging of impedance changes in rat somatosensory cerebral cortex with a resolution of 2 ms and < 200 μm during evoked potentials using epicortical arrays with 30 electrodes. Images were validated with local field potential recordings and current source-sink density analysis. Our results demonstrate that EIT can image neural activity in a volume 7 × 5 × 2 mm in somatosensory cerebral cortex with reduced invasiveness, greater resolution and imaging volume than other methods. Modeling indicates similar resolutions are feasible throughout the entire brain so this technique, uniquely, has the potential to image functional connectivity of cortical and subcortical structures. PMID:26348559

Altered spontaneous brain activity in Cushing's disease: a resting-state functional MRI study.

PubMed

Jiang, Hong; He, Na-Ying; Sun, Yu-Hao; Jian, Fang-Fang; Bian, Liu-Guan; Shen, Jian-Kang; Yan, Fu-Hua; Pan, Si-Jian; Sun, Qing-Fang

2017-03-01

Cushing's disease (CD) provides a unique and naturalist model for studying the influence of hypercortisolism on the human brain and the reversibility of these effects after resolution of the condition. This cross-sectional study used resting-state fMRI (rs-fMRI) to investigate the altered spontaneous brain activity in CD patients and the trends for potential reversibility after the resolution of the hypercortisolism. We also aim to determine the relationship of these changes with clinical characteristics and cortisol levels. Active CD patients (n = 18), remitted CD patients (n = 14) and healthy control subjects (n = 22) were included in this study. Amplitude of low-frequency fluctuation (ALFF) and regional homogeneity (ReHo) values were calculated to represent spontaneous brain activity. Our study resulted in three major findings: (i) active CD patients showed significantly altered spontaneous brain activity in the posterior cingulate cortex (PCC)/precuneus (PCu), occipital lobe (OC)/cerebellum, thalamus, right postcentral gyrus (PoCG) and left prefrontal cortex (PFC); (ii) trends for partial restoration of altered spontaneous brain activity after the resolution hypercortisolism were found in several brain regions; and (iii) active CD patients showed a significant correlation between cortisol levels and ALFF/ReHo values in the PCC/PCu, a small cluster in the OC and the right IPL. This study provides a new approach to investigating brain function abnormalities in patients with CD and enhances our understanding of the effect of hypercortisolism on the human brain. Furthermore, our explorative potential reversibility study of patients with CD may facilitate the development of future longitudinal studies. © 2016 John Wiley & Sons Ltd.

GATE simulation of a new design of pinhole SPECT system for small animal brain imaging

NASA Astrophysics Data System (ADS)

Uzun Ozsahin, D.; Bläckberg, L.; El Fakhri, G.; Sabet, H.

2017-01-01

Small animal SPECT imaging has gained an increased interest over the past decade since it is an excellent tool for developing new drugs and tracers. Therefore, there is a huge effort on the development of cost-effective SPECT detectors with high capabilities. The aim of this study is to simulate the performance characteristics of new designs for a cost effective, stationary SPECT system dedicated to small animal imaging with a focus on mice brain. The conceptual design of this SPECT system platform, Stationary Small Animal SSA-SPECT, is to use many pixelated CsI:TI detector modules with 0.4 mm × 0.4 mm pixels in order to achieve excellent intrinsic detector resolution where each module is backed by a single pinhole collimator with 0.3 mm hole diameter. In this work, we present the simulation results of four variations of the SSA-SPECT platform where the number of detector modules and FOV size is varied while keeping the detector size and collimator hole size constant. Using the NEMA NU-4 protocol, we performed spatial resolution, sensitivity, image quality simulations followed by a Derenzo-like phantom evaluation. The results suggest that all four SSA-SPECT systems can provide better than 0.063% system sensitivity and < 1.5 mm FWHM spatial resolution without resolution recovery or other correction techniques. Specifically, SSA-SPECT-1 showed a system sensitivity of 0.09% in combination with 1.1 mm FWHM spatial resolution.

Enhancement of Temporal Resolution and BOLD Sensitivity in Real-Time fMRI using Multi-Slab Echo-Volumar Imaging

PubMed Central

Posse, Stefan; Ackley, Elena; Mutihac, Radu; Rick, Jochen; Shane, Matthew; Murray-Krezan, Cristina; Zaitsev, Maxim; Speck, Oliver

2012-01-01

In this study, a new approach to high-speed fMRI using multi-slab echo-volumar imaging (EVI) is developed that minimizes geometrical image distortion and spatial blurring, and enables nonaliased sampling of physiological signal fluctuation to increase BOLD sensitivity compared to conventional echo-planar imaging (EPI). Real-time fMRI using whole brain 4-slab EVI with 286 ms temporal resolution (4 mm isotropic voxel size) and partial brain 2-slab EVI with 136 ms temporal resolution (4×4×6 mm3 voxel size) was performed on a clinical 3 Tesla MRI scanner equipped with 12-channel head coil. Four-slab EVI of visual and motor tasks significantly increased mean (visual: 96%, motor: 66%) and maximum t-score (visual: 263%, motor: 124%) and mean (visual: 59%, motor: 131%) and maximum (visual: 29%, motor: 67%) BOLD signal amplitude compared with EPI. Time domain moving average filtering (2 s width) to suppress physiological noise from cardiac and respiratory fluctuations further improved mean (visual: 196%, motor: 140%) and maximum (visual: 384%, motor: 200%) t-scores and increased extents of activation (visual: 73%, motor: 70%) compared to EPI. Similar sensitivity enhancement, which is attributed to high sampling rate at only moderately reduced temporal signal-to-noise ratio (mean: − 52%) and longer sampling of the BOLD effect in the echo-time domain compared to EPI, was measured in auditory cortex. Two-slab EVI further improved temporal resolution for measuring task-related activation and enabled mapping of five major resting state networks (RSNs) in individual subjects in 5 min scans. The bilateral sensorimotor, the default mode and the occipital RSNs were detectable in time frames as short as 75 s. In conclusion, the high sampling rate of real-time multi-slab EVI significantly improves sensitivity for studying the temporal dynamics of hemodynamic responses and for characterizing functional networks at high field strength in short measurement times. PMID:22398395

4D microvascular imaging based on ultrafast Doppler tomography.

PubMed

Demené, Charlie; Tiran, Elodie; Sieu, Lim-Anna; Bergel, Antoine; Gennisson, Jean Luc; Pernot, Mathieu; Deffieux, Thomas; Cohen, Ivan; Tanter, Mickael

2016-02-15

4D ultrasound microvascular imaging was demonstrated by applying ultrafast Doppler tomography (UFD-T) to the imaging of brain hemodynamics in rodents. In vivo real-time imaging of the rat brain was performed using ultrasonic plane wave transmissions at very high frame rates (18,000 frames per second). Such ultrafast frame rates allow for highly sensitive and wide-field-of-view 2D Doppler imaging of blood vessels far beyond conventional ultrasonography. Voxel anisotropy (100 μm × 100 μm × 500 μm) was corrected for by using a tomographic approach, which consisted of ultrafast acquisitions repeated for different imaging plane orientations over multiple cardiac cycles. UFT-D allows for 4D dynamic microvascular imaging of deep-seated vasculature (up to 20 mm) with a very high 4D resolution (respectively 100 μm × 100 μm × 100 μm and 10 ms) and high sensitivity to flow in small vessels (>1 mm/s) for a whole-brain imaging technique without requiring any contrast agent. 4D ultrasound microvascular imaging in vivo could become a valuable tool for the study of brain hemodynamics, such as cerebral flow autoregulation or vascular remodeling after ischemic stroke recovery, and, more generally, tumor vasculature response to therapeutic treatment. Copyright © 2015 Elsevier Inc. All rights reserved.

Pan-neuronal calcium imaging with cellular resolution in freely swimming zebrafish.

PubMed

Kim, Dal Hyung; Kim, Jungsoo; Marques, João C; Grama, Abhinav; Hildebrand, David G C; Gu, Wenchao; Li, Jennifer M; Robson, Drew N

2017-11-01

Calcium imaging with cellular resolution typically requires an animal to be tethered under a microscope, which substantially restricts the range of behaviors that can be studied. To expand the behavioral repertoire amenable to imaging, we have developed a tracking microscope that enables whole-brain calcium imaging with cellular resolution in freely swimming larval zebrafish. This microscope uses infrared imaging to track a target animal in a behavior arena. On the basis of the predicted trajectory of the animal, we applied optimal control theory to a motorized stage system to cancel brain motion in three dimensions. We combined this motion-cancellation system with differential illumination focal filtering, a variant of HiLo microscopy, which enabled us to image the brain of a freely swimming larval zebrafish for more than an hour. This work expands the repertoire of natural behaviors that can be studied with cellular-resolution calcium imaging to potentially include spatial navigation, social behavior, feeding and reward.

Two-photon microscope for multisite microphotolysis of caged neurotransmitters in acute brain slices

PubMed Central

Losavio, Bradley E.; Iyer, Vijay; Saggau, Peter

2009-01-01

We developed a two-photon microscope optimized for physiologically manipulating single neurons through their postsynaptic receptors. The optical layout fulfills the stringent design criteria required for high-speed, high-resolution imaging in scattering brain tissue with minimal photodamage. We detail the practical compensation of spectral and temporal dispersion inherent in fast laser beam scanning with acousto-optic deflectors, as well as a set of biological protocols for visualizing nearly diffraction-limited structures and delivering physiological synaptic stimuli. The microscope clearly resolves dendritic spines and evokes electrophysiological transients in single neurons that are similar to endogenous responses. This system enables the study of multisynaptic integration and will assist our understanding of single neuron function and dendritic computation. PMID:20059271

Early parental care is important for hippocampal maturation: evidence from brain morphology in humans.

PubMed

Rao, Hengyi; Betancourt, Laura; Giannetta, Joan M; Brodsky, Nancy L; Korczykowski, Marc; Avants, Brian B; Gee, James C; Wang, Jiongjiong; Hurt, Hallam; Detre, John A; Farah, Martha J

2010-01-01

The effects of early life experience on later brain structure and function have been studied extensively in animals, yet the relationship between childhood experience and normal brain development in humans remains largely unknown. Using a unique longitudinal data set including ecologically valid in-home measures of early experience during childhood (at age 4 and 8 years) and high-resolution structural brain imaging during adolescence (mean age 14 years), we examined the effects on later brain morphology of two dimensions of early experience: parental nurturance and environmental stimulation. Parental nurturance at age 4 predicts the volume of the left hippocampus in adolescence, with better nurturance associated with smaller hippocampal volume. In contrast, environmental stimulation did not correlate with hippocampal volume. Moreover, the association between hippocampal volume and parental nurturance disappears at age 8, supporting the existence of a sensitive developmental period for brain maturation. These findings indicate that variation in normal childhood experience is associated with differences in brain morphology, and hippocampal volume is specifically associated with early parental nurturance. Our results provide neuroimaging evidence supporting the important role of warm parental care during early childhood for brain maturation.

Adaptation, perceptual learning, and plasticity of brain functions.

PubMed

Horton, Jonathan C; Fahle, Manfred; Mulder, Theo; Trauzettel-Klosinski, Susanne

2017-03-01

The capacity for functional restitution after brain damage is quite different in the sensory and motor systems. This series of presentations highlights the potential for adaptation, plasticity, and perceptual learning from an interdisciplinary perspective. The chances for restitution in the primary visual cortex are limited. Some patterns of visual field loss and recovery after stroke are common, whereas others are impossible, which can be explained by the arrangement and plasticity of the cortical map. On the other hand, compensatory mechanisms are effective, can occur spontaneously, and can be enhanced by training. In contrast to the human visual system, the motor system is highly flexible. This is based on special relationships between perception and action and between cognition and action. In addition, the healthy adult brain can learn new functions, e.g. increasing resolution above the retinal one. The significance of these studies for rehabilitation after brain damage will be discussed.

Whole-brain activity maps reveal stereotyped, distributed networks for visuomotor behavior.

PubMed

Portugues, Ruben; Feierstein, Claudia E; Engert, Florian; Orger, Michael B

2014-03-19

Most behaviors, even simple innate reflexes, are mediated by circuits of neurons spanning areas throughout the brain. However, in most cases, the distribution and dynamics of firing patterns of these neurons during behavior are not known. We imaged activity, with cellular resolution, throughout the whole brains of zebrafish performing the optokinetic response. We found a sparse, broadly distributed network that has an elaborate but ordered pattern, with a bilaterally symmetrical organization. Activity patterns fell into distinct clusters reflecting sensory and motor processing. By correlating neuronal responses with an array of sensory and motor variables, we find that the network can be clearly divided into distinct functional modules. Comparing aligned data from multiple fish, we find that the spatiotemporal activity dynamics and functional organization are highly stereotyped across individuals. These experiments systematically reveal the functional architecture of neural circuits underlying a sensorimotor behavior in a vertebrate brain. Copyright © 2014 Elsevier Inc. All rights reserved.

In vivo three-photon microscopy of subcortical structures within an intact mouse brain

NASA Astrophysics Data System (ADS)

Horton, Nicholas G.; Wang, Ke; Kobat, Demirhan; Clark, Catharine G.; Wise, Frank W.; Schaffer, Chris B.; Xu, Chris

2013-03-01

Two-photon fluorescence microscopy enables scientists in various fields including neuroscience, embryology and oncology to visualize in vivo and ex vivo tissue morphology and physiology at a cellular level deep within scattering tissue. However, tissue scattering limits the maximum imaging depth of two-photon fluorescence microscopy to the cortical layer within mouse brain, and imaging subcortical structures currently requires the removal of overlying brain tissue or the insertion of optical probes. Here, we demonstrate non-invasive, high-resolution, in vivo imaging of subcortical structures within an intact mouse brain using three-photon fluorescence microscopy at a spectral excitation window of 1,700 nm. Vascular structures as well as red fluorescent protein-labelled neurons within the mouse hippocampus are imaged. The combination of the long excitation wavelength and the higher-order nonlinear excitation overcomes the limitations of two-photon fluorescence microscopy, enabling biological investigations to take place at a greater depth within tissue.

From a meso- to micro-scale connectome: array tomography and mGRASP

PubMed Central

Rah, Jong-Cheol; Feng, Linqing; Druckmann, Shaul; Lee, Hojin; Kim, Jinhyun

2015-01-01

Mapping mammalian synaptic connectivity has long been an important goal of neuroscience because knowing how neurons and brain areas are connected underpins an understanding of brain function. Meeting this goal requires advanced techniques with single synapse resolution and large-scale capacity, especially at multiple scales tethering the meso- and micro-scale connectome. Among several advanced LM-based connectome technologies, Array Tomography (AT) and mammalian GFP-Reconstitution Across Synaptic Partners (mGRASP) can provide relatively high-throughput mapping synaptic connectivity at multiple scales. AT- and mGRASP-assisted circuit mapping (ATing and mGRASPing), combined with techniques such as retrograde virus, brain clearing techniques, and activity indicators will help unlock the secrets of complex neural circuits. Here, we discuss these useful new tools to enable mapping of brain circuits at multiple scales, some functional implications of spatial synaptic distribution, and future challenges and directions of these endeavors. PMID:26089781

Regional registration of [6-14C]glucose metabolism during brain activation of α-syntrophin knockout mice

PubMed Central

Cruz, Nancy F.; Ball, Kelly K.; Froehner, Stanley C.; Adams, Marvin E.; Dienel, Gerald A.

2013-01-01

α-Syntrophin is a component of the dystrophin scaffold-protein complex that serves as an adaptor for recruitment of key proteins to the cytoplasmic side of plasma membranes. α-Syntrophin knockout (KO) causes loss of the polarized localization of aquaporin4 (AQP4) at astrocytic endfeet and interferes with water and K+ homeostasis. During brain activation, release of ions and metabolites from endfeet is anticipated to increase perivascular fluid osmolarity, AQP4-mediated osmotic water flow from endfeet, and metabolite washout from brain. This study tests the hypothesis that reduced levels of endfoot AQP4 increase retention of [14C]metabolites during sensory stimulation. Conscious KO and wildtype mice were pulse-labeled with [6-14C]glucose during unilateral acoustic stimulation or bilateral acoustic plus whisker stimulation, and label retention was assayed by computer-assisted brain imaging or analysis of [14C]metabolites in extracts, respectively. High-resolution autoradiographic assays detected a 17% side-to-side difference (P<0.05) in inferior colliculus of KO mice, not wildtype mice. However, there were no labeling differences between KO and wildtype mice for five major HPLC fractions from four dissected regions, presumably due to insufficient anatomical resolution. The results suggest a role for AQP4-mediated water flow in support of washout of metabolites, and underscore the need for greater understanding of astrocytic water and metabolite fluxes. PMID:23346911

Improving Focal Photostimulation of Cortical Neurons with Pre-derived Wavefront Correction

PubMed Central

Choy, Julian M. C.; Sané, Sharmila S.; Lee, Woei M.; Stricker, Christian; Bachor, Hans A.; Daria, Vincent R.

2017-01-01

Recent progress in neuroscience to image and investigate brain function has been made possible by impressive developments in optogenetic and opto-molecular tools. Such research requires advances in optical techniques for the delivery of light through brain tissue with high spatial resolution. The tissue causes distortions to the wavefront of the incoming light which broadens the focus and consequently reduces the intensity and degrades the resolution. Such effects are detrimental in techniques requiring focal stimulation. Adaptive wavefront correction has been demonstrated to compensate for these distortions. However, iterative derivation of the corrective wavefront introduces time constraints that limit its applicability to probe living cells. Here, we demonstrate that we can pre-determine and generalize a small set of Zernike modes to correct for aberrations of the light propagating through specific brain regions. A priori identification of a corrective wavefront is a direct and fast technique that improves the quality of the focus without the need for iterative adaptive wavefront correction. We verify our technique by measuring the efficiency of two-photon photolysis of caged neurotransmitters along the dendrites of a whole-cell patched neuron. Our results show that encoding the selected Zernike modes on the excitation light can improve light propagation through brain slices of rats as observed by the neuron's evoked excitatory post-synaptic potential in response to localized focal uncaging at the spines of the neuron's dendrites. PMID:28507508

Evaluating the effects of maternal alcohol consumption on murine fetal brain vasculature using optical coherence tomography.

PubMed

Raghunathan, Raksha; Wu, Chen; Singh, Manmohan; Liu, Chih-Hao; Miranda, Rajesh C; Larin, Kirill V

2018-05-01

Prenatal alcohol exposure (PAE) can result in a range of anomalies including brain and behavioral dysfunctions, collectively termed fetal alcohol spectrum disorder. PAE during the 1st and 2nd trimester is common, and research in animal models has documented significant neural developmental deficits associated with PAE during this period. However, little is known about the immediate effects of PAE on fetal brain vasculature. In this study, we used in utero speckle variance optical coherence tomography, a high spatial- and temporal-resolution imaging modality, to evaluate dynamic changes in microvasculature of the 2nd trimester equivalent murine fetal brain, minutes after binge-like maternal alcohol exposure. Acute binge-like PAE resulted in a rapid (<1 hour) and significant decrease (P < .001) in vessel diameter as compared to the sham group. The data show that a single binge-like maternal alcohol exposure resulted in swift vasoconstriction in fetal brain vessels during the critical period of neurogenesis. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Hyperspectral imaging solutions for brain tissue metabolic and hemodynamic monitoring: past, current and future developments

NASA Astrophysics Data System (ADS)

Giannoni, Luca; Lange, Frédéric; Tachtsidis, Ilias

2018-04-01

Hyperspectral imaging (HSI) technologies have been used extensively in medical research, targeting various biological phenomena and multiple tissue types. Their high spectral resolution over a wide range of wavelengths enables acquisition of spatial information corresponding to different light-interacting biological compounds. This review focuses on the application of HSI to monitor brain tissue metabolism and hemodynamics in life sciences. Different approaches involving HSI have been investigated to assess and quantify cerebral activity, mainly focusing on: (1) mapping tissue oxygen delivery through measurement of changes in oxygenated (HbO2) and deoxygenated (HHb) hemoglobin; and (2) the assessment of the cerebral metabolic rate of oxygen (CMRO2) to estimate oxygen consumption by brain tissue. Finally, we introduce future perspectives of HSI of brain metabolism, including its potential use for imaging optical signals from molecules directly involved in cellular energy production. HSI solutions can provide remarkable insight in understanding cerebral tissue metabolism and oxygenation, aiding investigation on brain tissue physiological processes.

Major Shifts in Glial Regional Identity Are a Transcriptional Hallmark of Human Brain Aging.

PubMed

Soreq, Lilach; Rose, Jamie; Soreq, Eyal; Hardy, John; Trabzuni, Daniah; Cookson, Mark R; Smith, Colin; Ryten, Mina; Patani, Rickie; Ule, Jernej

2017-01-10

Gene expression studies suggest that aging of the human brain is determined by a complex interplay of molecular events, although both its region- and cell-type-specific consequences remain poorly understood. Here, we extensively characterized aging-altered gene expression changes across ten human brain regions from 480 individuals ranging in age from 16 to 106 years. We show that astrocyte- and oligodendrocyte-specific genes, but not neuron-specific genes, shift their regional expression patterns upon aging, particularly in the hippocampus and substantia nigra, while the expression of microglia- and endothelial-specific genes increase in all brain regions. In line with these changes, high-resolution immunohistochemistry demonstrated decreased numbers of oligodendrocytes and of neuronal subpopulations in the aging brain cortex. Finally, glial-specific genes predict age with greater precision than neuron-specific genes, thus highlighting the need for greater mechanistic understanding of neuron-glia interactions in aging and late-life diseases. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Effect of Experimental Thyrotoxicosis on Brain Gray Matter: A Voxel-Based Morphometry Study.

PubMed

Göbel, Anna; Heldmann, Marcus; Göttlich, Martin; Dirk, Anna-Luise; Brabant, Georg; Münte, Thomas F

2015-09-01

Hyper-as well hypothyroidism have an effect on behavior and brain function. Moreover, during development thyroid hormones influence brain structure. This study aimed to demonstrate an effect of experimentally induced hyperthyroidism on brain gray matter in healthy adult humans. High-resolution 3D T1-weighted images were acquired in 29 healthy young subjects prior to as well as after receiving 250 µg of T4 per day for 8 weeks. Voxel-based morphometry analysis was performed using Statistical Parametric Mapping 8 (SPM8). Laboratory testing confirmed the induction of hyperthyroidism. In the hyperthyroid condition, gray matter volumes were increased in the right posterior cerebellum (lobule VI) and decreased in the bilateral visual cortex and anterior cerebellum (lobules I-IV) compared to the euthyroid condition. Our study provides evidence that short periods of hyperthyroidism induce distinct alterations in brain structures of cerebellar regions that have been associated with sensorimotor functions as well as working memory in the literature.

A study of the comparative anatomy of the brain of domestic ruminants using magnetic resonance imaging.

PubMed

Schmidt, M J; Langen, N; Klumpp, S; Nasirimanesh, F; Shirvanchi, P; Ondreka, N; Kramer, M

2012-01-01

Although magnetic resonance imaging has been used to examine the brain of domestic ruminants, detailed information relating the precise anatomical features in these species is lacking. In this study the brain structures of calves (Bos taurus domesticus), sheep (Ovis aries), goats (Capra hircus) and a mesaticephalic dog (Canis lupis familiaris) were examined using T2-weighed Turbo Spin Echo sequences; three-dimensional models based on high-resolution gradient echo scans were used to identify brain sulci and gyri in two-dimensional images. The ruminant brains examined were similar in structure and organisation to those of other mammals but particular features included the deep depression of the insula and the pronounced gyri of the cortices, the dominant position of the visual (optic nerve, optic chiasm and rostral colliculus) and olfactory (olfactory bulb, olfactory tracts and piriform lobe) systems, and the relatively large size of the diencephalon. Copyright © 2010 Elsevier Ltd. All rights reserved.

Optical Coherence Tomography for Brain Imaging and Developmental Biology

PubMed Central

Men, Jing; Huang, Yongyang; Solanki, Jitendra; Zeng, Xianxu; Alex, Aneesh; Jerwick, Jason; Zhang, Zhan; Tanzi, Rudolph E.; Li, Airong; Zhou, Chao

2016-01-01

Optical coherence tomography (OCT) is a promising research tool for brain imaging and developmental biology. Serving as a three-dimensional optical biopsy technique, OCT provides volumetric reconstruction of brain tissues and embryonic structures with micrometer resolution and video rate imaging speed. Functional OCT enables label-free monitoring of hemodynamic and metabolic changes in the brain in vitro and in vivo in animal models. Due to its non-invasiveness nature, OCT enables longitudinal imaging of developing specimens in vivo without potential damage from surgical operation, tissue fixation and processing, and staining with exogenous contrast agents. In this paper, various OCT applications in brain imaging and developmental biology are reviewed, with a particular focus on imaging heart development. In addition, we report findings on the effects of a circadian gene (Clock) and high-fat-diet on heart development in Drosophila melanogaster. These findings contribute to our understanding of the fundamental mechanisms connecting circadian genes and obesity to heart development and cardiac diseases. PMID:27721647

High-resolution, high-throughput imaging with a multibeam scanning electron microscope.

PubMed

Eberle, A L; Mikula, S; Schalek, R; Lichtman, J; Knothe Tate, M L; Zeidler, D

2015-08-01

Electron-electron interactions and detector bandwidth limit the maximal imaging speed of single-beam scanning electron microscopes. We use multiple electron beams in a single column and detect secondary electrons in parallel to increase the imaging speed by close to two orders of magnitude and demonstrate imaging for a variety of samples ranging from biological brain tissue to semiconductor wafers. © 2015 The Authors Journal of Microscopy © 2015 Royal Microscopical Society.

Visible rodent brain-wide networks at single-neuron resolution

PubMed Central

Yuan, Jing; Gong, Hui; Li, Anan; Li, Xiangning; Chen, Shangbin; Zeng, Shaoqun; Luo, Qingming

2015-01-01

There are some unsolvable fundamental questions, such as cell type classification, neural circuit tracing and neurovascular coupling, though great progresses are being made in neuroscience. Because of the structural features of neurons and neural circuits, the solution of these questions needs us to break through the current technology of neuroanatomy for acquiring the exactly fine morphology of neuron and vessels and tracing long-distant circuit at axonal resolution in the whole brain of mammals. Combined with fast-developing labeling techniques, efficient whole-brain optical imaging technology emerging at the right moment presents a huge potential in the structure and function research of specific-function neuron and neural circuit. In this review, we summarize brain-wide optical tomography techniques, review the progress on visible brain neuronal/vascular networks benefit from these novel techniques, and prospect the future technical development. PMID:26074784

Cyberinfrastructure for the digital brain: spatial standards for integrating rodent brain atlases

PubMed Central

Zaslavsky, Ilya; Baldock, Richard A.; Boline, Jyl

2014-01-01

Biomedical research entails capture and analysis of massive data volumes and new discoveries arise from data-integration and mining. This is only possible if data can be mapped onto a common framework such as the genome for genomic data. In neuroscience, the framework is intrinsically spatial and based on a number of paper atlases. This cannot meet today's data-intensive analysis and integration challenges. A scalable and extensible software infrastructure that is standards based but open for novel data and resources, is required for integrating information such as signal distributions, gene-expression, neuronal connectivity, electrophysiology, anatomy, and developmental processes. Therefore, the International Neuroinformatics Coordinating Facility (INCF) initiated the development of a spatial framework for neuroscience data integration with an associated Digital Atlasing Infrastructure (DAI). A prototype implementation of this infrastructure for the rodent brain is reported here. The infrastructure is based on a collection of reference spaces to which data is mapped at the required resolution, such as the Waxholm Space (WHS), a 3D reconstruction of the brain generated using high-resolution, multi-channel microMRI. The core standards of the digital atlasing service-oriented infrastructure include Waxholm Markup Language (WaxML): XML schema expressing a uniform information model for key elements such as coordinate systems, transformations, points of interest (POI)s, labels, and annotations; and Atlas Web Services: interfaces for querying and updating atlas data. The services return WaxML-encoded documents with information about capabilities, spatial reference systems (SRSs) and structures, and execute coordinate transformations and POI-based requests. Key elements of INCF-DAI cyberinfrastructure have been prototyped for both mouse and rat brain atlas sources, including the Allen Mouse Brain Atlas, UCSD Cell-Centered Database, and Edinburgh Mouse Atlas Project. PMID:25309417

Cyberinfrastructure for the digital brain: spatial standards for integrating rodent brain atlases.

PubMed

Zaslavsky, Ilya; Baldock, Richard A; Boline, Jyl

2014-01-01

Biomedical research entails capture and analysis of massive data volumes and new discoveries arise from data-integration and mining. This is only possible if data can be mapped onto a common framework such as the genome for genomic data. In neuroscience, the framework is intrinsically spatial and based on a number of paper atlases. This cannot meet today's data-intensive analysis and integration challenges. A scalable and extensible software infrastructure that is standards based but open for novel data and resources, is required for integrating information such as signal distributions, gene-expression, neuronal connectivity, electrophysiology, anatomy, and developmental processes. Therefore, the International Neuroinformatics Coordinating Facility (INCF) initiated the development of a spatial framework for neuroscience data integration with an associated Digital Atlasing Infrastructure (DAI). A prototype implementation of this infrastructure for the rodent brain is reported here. The infrastructure is based on a collection of reference spaces to which data is mapped at the required resolution, such as the Waxholm Space (WHS), a 3D reconstruction of the brain generated using high-resolution, multi-channel microMRI. The core standards of the digital atlasing service-oriented infrastructure include Waxholm Markup Language (WaxML): XML schema expressing a uniform information model for key elements such as coordinate systems, transformations, points of interest (POI)s, labels, and annotations; and Atlas Web Services: interfaces for querying and updating atlas data. The services return WaxML-encoded documents with information about capabilities, spatial reference systems (SRSs) and structures, and execute coordinate transformations and POI-based requests. Key elements of INCF-DAI cyberinfrastructure have been prototyped for both mouse and rat brain atlas sources, including the Allen Mouse Brain Atlas, UCSD Cell-Centered Database, and Edinburgh Mouse Atlas Project.

Next-generation technologies for spatial proteomics: Integrating ultra-high speed MALDI-TOF and high mass resolution MALDI FTICR imaging mass spectrometry for protein analysis.

PubMed

Spraggins, Jeffrey M; Rizzo, David G; Moore, Jessica L; Noto, Michael J; Skaar, Eric P; Caprioli, Richard M

2016-06-01

MALDI imaging mass spectrometry is a powerful analytical tool enabling the visualization of biomolecules in tissue. However, there are unique challenges associated with protein imaging experiments including the need for higher spatial resolution capabilities, improved image acquisition rates, and better molecular specificity. Here we demonstrate the capabilities of ultra-high speed MALDI-TOF and high mass resolution MALDI FTICR IMS platforms as they relate to these challenges. High spatial resolution MALDI-TOF protein images of rat brain tissue and cystic fibrosis lung tissue were acquired at image acquisition rates >25 pixels/s. Structures as small as 50 μm were spatially resolved and proteins associated with host immune response were observed in cystic fibrosis lung tissue. Ultra-high speed MALDI-TOF enables unique applications including megapixel molecular imaging as demonstrated for lipid analysis of cystic fibrosis lung tissue. Additionally, imaging experiments using MALDI FTICR IMS were shown to produce data with high mass accuracy (<5 ppm) and resolving power (∼75 000 at m/z 5000) for proteins up to ∼20 kDa. Analysis of clear cell renal cell carcinoma using MALDI FTICR IMS identified specific proteins localized to healthy tissue regions, within the tumor, and also in areas of increased vascularization around the tumor. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Tracking brain motion during the cardiac cycle using spiral cine-DENSE MRI

PubMed Central

Zhong, Xiaodong; Meyer, Craig H.; Schlesinger, David J.; Sheehan, Jason P.; Epstein, Frederick H.; Larner, James M.; Benedict, Stanley H.; Read, Paul W.; Sheng, Ke; Cai, Jing

2009-01-01

Cardiac-synchronized brain motion is well documented, but the accurate measurement of such motion on the pixel-by-pixel basis has been hampered by the lack of proper imaging technique. In this article, the authors present the implementation of an autotracking spiral cine displacement-encoded stimulation echo (DENSE) magnetic resonance imaging (MRI) technique for the measurement of pulsatile brain motion during the cardiac cycle. Displacement-encoded dynamic MR images of three healthy volunteers were acquired throughout the cardiac cycle using the spiral cine-DENSE pulse sequence gated to the R wave of an electrocardiogram. Pixelwise Lagrangian displacement maps were computed, and 2D displacement as a function of time was determined for selected regions of interests. Different intracranial structures exhibited characteristic motion amplitude, direction, and pattern throughout the cardiac cycle. Time-resolved displacement curves revealed the pathway of pulsatile motion from brain stem to peripheral brain lobes. These preliminary results demonstrated that the spiral cine-DENSE MRI technique can be used to measure cardiac-synchronized pulsatile brain motion on the pixel-by-pixel basis with high temporal∕spatial resolution and sensitivity. PMID:19746774

Autism BrainNet: A network of postmortem brain banks established to facilitate autism research.

PubMed

Amaral, David G; Anderson, Matthew P; Ansorge, Olaf; Chance, Steven; Hare, Carolyn; Hof, Patrick R; Miller, Melissa; Nagakura, Ikue; Pickett, Jane; Schumann, Cynthia; Tamminga, Carol

2018-01-01

Autism spectrum disorder (ASD or autism) is a neurodevelopmental condition that affects over 1% of the population worldwide. Developing effective preventions and treatments for autism will depend on understanding the genetic perturbations and underlying neuropathology of the disorder. While evidence from magnetic resonance imaging and other noninvasive techniques points to altered development and organization of the autistic brain, these tools lack the resolution for identifying the cellular and molecular underpinnings of the disorder. Postmortem studies of high-quality human brain tissue currently represent the only viable option to pursuing these types of studies. However, the availability of high-quality ASD brain tissue has been extremely limited. Here we describe the establishment of a privately funded tissue bank, Autism BrainNet, a network of brain collection sites that work in a coordinated fashion to develop an adequate library of human postmortem brain tissues. Autism BrainNet was initiated as a collaboration between the Simons Foundation and Autism Speaks, and is currently funded by the Simons Foundation Autism Research Initiative. Autism BrainNet has collection sites (nodes) in California, Texas, New York, and Massachusetts; an affiliated, international node is located in Oxford, England. All donations to this network become part of a consolidated pool of tissue that is distributed to qualified investigators worldwide to carry out autism research. An essential component of this program is a widespread outreach program that highlights the need for postmortem brain donations to families affected by autism, led by the Autism Science Foundation. Challenges include an outreach campaign that deals with a disorder beginning in early childhood, collecting an adequate number of donations to deal with the high level of biologic heterogeneity of autism, and preparing this limited resource for optimal distribution to the greatest number of investigators. Copyright © 2018 Elsevier B.V. All rights reserved.

Enhancing the performance of the light field microscope using wavefront coding

PubMed Central

Cohen, Noy; Yang, Samuel; Andalman, Aaron; Broxton, Michael; Grosenick, Logan; Deisseroth, Karl; Horowitz, Mark; Levoy, Marc

2014-01-01

Light field microscopy has been proposed as a new high-speed volumetric computational imaging method that enables reconstruction of 3-D volumes from captured projections of the 4-D light field. Recently, a detailed physical optics model of the light field microscope has been derived, which led to the development of a deconvolution algorithm that reconstructs 3-D volumes with high spatial resolution. However, the spatial resolution of the reconstructions has been shown to be non-uniform across depth, with some z planes showing high resolution and others, particularly at the center of the imaged volume, showing very low resolution. In this paper, we enhance the performance of the light field microscope using wavefront coding techniques. By including phase masks in the optical path of the microscope we are able to address this non-uniform resolution limitation. We have also found that superior control over the performance of the light field microscope can be achieved by using two phase masks rather than one, placed at the objective’s back focal plane and at the microscope’s native image plane. We present an extended optical model for our wavefront coded light field microscope and develop a performance metric based on Fisher information, which we use to choose adequate phase masks parameters. We validate our approach using both simulated data and experimental resolution measurements of a USAF 1951 resolution target; and demonstrate the utility for biological applications with in vivo volumetric calcium imaging of larval zebrafish brain. PMID:25322056

Enhancing the performance of the light field microscope using wavefront coding.

PubMed

Cohen, Noy; Yang, Samuel; Andalman, Aaron; Broxton, Michael; Grosenick, Logan; Deisseroth, Karl; Horowitz, Mark; Levoy, Marc

2014-10-06

Light field microscopy has been proposed as a new high-speed volumetric computational imaging method that enables reconstruction of 3-D volumes from captured projections of the 4-D light field. Recently, a detailed physical optics model of the light field microscope has been derived, which led to the development of a deconvolution algorithm that reconstructs 3-D volumes with high spatial resolution. However, the spatial resolution of the reconstructions has been shown to be non-uniform across depth, with some z planes showing high resolution and others, particularly at the center of the imaged volume, showing very low resolution. In this paper, we enhance the performance of the light field microscope using wavefront coding techniques. By including phase masks in the optical path of the microscope we are able to address this non-uniform resolution limitation. We have also found that superior control over the performance of the light field microscope can be achieved by using two phase masks rather than one, placed at the objective's back focal plane and at the microscope's native image plane. We present an extended optical model for our wavefront coded light field microscope and develop a performance metric based on Fisher information, which we use to choose adequate phase masks parameters. We validate our approach using both simulated data and experimental resolution measurements of a USAF 1951 resolution target; and demonstrate the utility for biological applications with in vivo volumetric calcium imaging of larval zebrafish brain.

A novel and rapid method for obtaining high titre intact prion strains from mammalian brain.

PubMed

Wenborn, Adam; Terry, Cassandra; Gros, Nathalie; Joiner, Susan; D'Castro, Laura; Panico, Silvia; Sells, Jessica; Cronier, Sabrina; Linehan, Jacqueline M; Brandner, Sebastian; Saibil, Helen R; Collinge, John; Wadsworth, Jonathan D F

2015-05-07

Mammalian prions exist as multiple strains which produce characteristic and highly reproducible phenotypes in defined hosts. How this strain diversity is encoded by a protein-only agent remains one of the most interesting and challenging questions in biology with wide relevance to understanding other diseases involving the aggregation or polymerisation of misfolded host proteins. Progress in understanding mammalian prion strains has however been severely limited by the complexity and variability of the methods used for their isolation from infected tissue and no high resolution structures have yet been reported. Using high-throughput cell-based prion bioassay to re-examine prion purification from first principles we now report the isolation of prion strains to exceptional levels of purity from small quantities of infected brain and demonstrate faithful retention of biological and biochemical strain properties. The method's effectiveness and simplicity should facilitate its wide application and expedite structural studies of prions.

A novel and rapid method for obtaining high titre intact prion strains from mammalian brain

PubMed Central

Wenborn, Adam; Terry, Cassandra; Gros, Nathalie; Joiner, Susan; D’Castro, Laura; Panico, Silvia; Sells, Jessica; Cronier, Sabrina; Linehan, Jacqueline M.; Brandner, Sebastian; Saibil, Helen R.; Collinge, John; Wadsworth, Jonathan D. F.

2015-01-01

Mammalian prions exist as multiple strains which produce characteristic and highly reproducible phenotypes in defined hosts. How this strain diversity is encoded by a protein-only agent remains one of the most interesting and challenging questions in biology with wide relevance to understanding other diseases involving the aggregation or polymerisation of misfolded host proteins. Progress in understanding mammalian prion strains has however been severely limited by the complexity and variability of the methods used for their isolation from infected tissue and no high resolution structures have yet been reported. Using high-throughput cell-based prion bioassay to re-examine prion purification from first principles we now report the isolation of prion strains to exceptional levels of purity from small quantities of infected brain and demonstrate faithful retention of biological and biochemical strain properties. The method’s effectiveness and simplicity should facilitate its wide application and expedite structural studies of prions. PMID:25950908

Neuroanatomical Markers of Social Hierarchy Recognition in Humans: A Combined ERP/MRI Study.

PubMed

Santamaría-García, Hernando; Burgaleta, Miguel; Sebastián-Gallés, Nuria

2015-07-29

Social hierarchy is an ubiquitous principle of social organization across animal species. Although some progress has been made in our understanding of how humans infer hierarchical identity, the neuroanatomical basis for perceiving key social dimensions of others remains unexplored. Here, we combined event-related potentials and structural MRI to reveal the neuroanatomical substrates of early status recognition. We designed a covertly simulated hierarchical setting in which participants performed a task either with a superior or with an inferior player. Participants showed higher amplitude in the N170 component when presented with a picture of a superior player compared with an inferior player. Crucially, the magnitude of this effect correlated with brain morphology of the posterior cingulate cortex, superior temporal gyrus, insula, fusiform gyrus, and caudate nucleus. We conclude that early recognition of social hierarchies relies on the structural properties of a network involved in the automatic recognition of social identity. Humans can perceive social hierarchies very rapidly, an ability that is key for social interactions. However, some individuals are more sensitive to hierarchical information than others. Currently, it is unknown how brain structure supports such fast-paced processes of social hierarchy perception and their individual differences. Here, we addressed this issue for the first time by combining the high temporal resolution of event-related potentials (ERPs) and the high spatial resolution of structural MRI. This methodological approach allowed us to unveil a novel association between ERP neuromarkers of social hierarchy perception and the morphology of several cortical and subcortical brain regions typically assumed to play a role in automatic processes of social cognition. Our results are a step forward in our understanding of the human social brain. Copyright © 2015 the authors 0270-6474/15/3510843-08$15.00/0.

Direct estimation of tracer-kinetic parameter maps from highly undersampled brain dynamic contrast enhanced MRI.

PubMed

Guo, Yi; Lingala, Sajan Goud; Zhu, Yinghua; Lebel, R Marc; Nayak, Krishna S

2017-10-01

The purpose of this work was to develop and evaluate a T 1 -weighted dynamic contrast enhanced (DCE) MRI methodology where tracer-kinetic (TK) parameter maps are directly estimated from undersampled (k,t)-space data. The proposed reconstruction involves solving a nonlinear least squares optimization problem that includes explicit use of a full forward model to convert parameter maps to (k,t)-space, utilizing the Patlak TK model. The proposed scheme is compared against an indirect method that creates intermediate images by parallel imaging and compressed sensing before to TK modeling. Thirteen fully sampled brain tumor DCE-MRI scans with 5-second temporal resolution are retrospectively undersampled at rates R = 20, 40, 60, 80, and 100 for each dynamic frame. TK maps are quantitatively compared based on root mean-squared-error (rMSE) and Bland-Altman analysis. The approach is also applied to four prospectively R = 30 undersampled whole-brain DCE-MRI data sets. In the retrospective study, the proposed method performed statistically better than indirect method at R ≥ 80 for all 13 cases. This approach provided restoration of TK parameter values with less errors in tumor regions of interest, an improvement compared to a state-of-the-art indirect method. Applied prospectively, the proposed method provided whole-brain, high-resolution TK maps with good image quality. Model-based direct estimation of TK maps from k,t-space DCE-MRI data is feasible and is compatible up to 100-fold undersampling. Magn Reson Med 78:1566-1578, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

Precise Spatiotemporal Control of Optogenetic Activation Using an Acousto-Optic Device

PubMed Central

Guo, Yanmeng; Song, Peipei; Zhang, Xiaohui; Zeng, Shaoqun; Wang, Zuoren

2011-01-01

Light activation and inactivation of neurons by optogenetic techniques has emerged as an important tool for studying neural circuit function. To achieve a high resolution, new methods are being developed to selectively manipulate the activity of individual neurons. Here, we report that the combination of an acousto-optic device (AOD) and single-photon laser was used to achieve rapid and precise spatiotemporal control of light stimulation at multiple points in a neural circuit with millisecond time resolution. The performance of this system in activating ChIEF expressed on HEK 293 cells as well as cultured neurons was first evaluated, and the laser stimulation patterns were optimized. Next, the spatiotemporally selective manipulation of multiple neurons was achieved in a precise manner. Finally, we demonstrated the versatility of this high-resolution method in dissecting neural circuits both in the mouse cortical slice and the Drosophila brain in vivo. Taken together, our results show that the combination of AOD-assisted laser stimulation and optogenetic tools provides a flexible solution for manipulating neuronal activity at high efficiency and with high temporal precision. PMID:22174813

A high-resolution optical imaging system for obtaining the serial transverse section images of biologic tissue

NASA Astrophysics Data System (ADS)

Wu, Li; Zhang, Bin; Wu, Ping; Liu, Qian; Gong, Hui

2007-05-01

A high-resolution optical imaging system was designed and developed to obtain the serial transverse section images of the biologic tissue, such as the mouse brain, in which new knife-edge imaging technology, high-speed and high-sensitive line-scan CCD and linear air bearing stages were adopted and incorporated with an OLYMPUS microscope. The section images on the tip of the knife-edge were synchronously captured by the reflection imaging in the microscope while cutting the biologic tissue. The biologic tissue can be sectioned at interval of 250 nm with the same resolution of the transverse section images obtained in x and y plane. And the cutting job can be automatically finished based on the control program wrote specially in advance, so we save the mass labor of the registration of the vast images data. In addition, by using this system a larger sample can be cut than conventional ultramicrotome so as to avoid the loss of the tissue structure information because of splitting the tissue sample to meet the size request of the ultramicrotome.

Development of a circular shape Si-PM-based detector ring for breast-dedicated PET system

NASA Astrophysics Data System (ADS)

Nakanishi, Kouhei; Yamamoto, Seiichi; Watabe, Hiroshi; Abe, Shinji; Fujita, Naotoshi; Kato, Katsuhiko

2018-02-01

In clinical situations, various breast-dedicated positron emission tomography (PET) systems have been used. However, clinical breast-dedicated PET systems have polygonal detector ring. Polygonal detector ring sometimes causes image artifact, so complicated reconstruction algorithm is needed to reduce artifact. Consequently, we developed a circular detector ring for breast-dedicated PET to obtain images without artifact using a simple reconstruction algorithm. We used Lu1.9Gd0.1SiO5 (LGSO) scintillator block which was made of 1.5 x 1.9 x 15 mm pixels that were arranged in an 8 x 24 matrix. As photodetectors, we used silicon photomultiplier (Si-PM) arrays whose channel size was 3 x 3 mm. A detector unit was composed of four scintillator blocks, 16 Si-PM arrays and a light guide. The developed detector unit had angled configuration since the light guide was bending. A detector unit had three gaps with an angle of 5.625° between scintillator blocks. With these configurations, we could arrange 64 scintillator blocks in nearly circular shape (regular 64-sided polygon) using 16 detector units. The use of the smaller number of detector units could reduce the size of the front-end electronics circuits. The inner diameter of the developed detector ring was 260 mm. This size was similar to those of brain PET systems, so our breast-dedicated PET detector ring can measure not only breast but also brain. Measured radial, tangential and axial spatial resolution of the detector ring reconstructed by the filtered back-projection (FBP) algorithm were 2.1 mm FWHM, 2.0 mm FWHM and 1.7 mm FWHM at center of field of view (FOV), respectively. The sensitivity was 2.0% at center of the axial FOV. With the developed detector ring, we could obtain high resolution image of the breast phantom and the brain phantom. We conclude that our developed Si-PM-based detector ring is promising for a high resolution breast-dedicated PET system that can also be used for brain PET system.

The subcortical role of language processing. High level linguistic features such as ambiguity-resolution and the human brain; an fMRI study.

PubMed

Ketteler, Daniel; Kastrau, Frank; Vohn, Rene; Huber, Walter

2008-02-15

In the present study, we were interested in the neurofunctional representations of ambiguity processing by using functional magnetic resonance imaging (fMRI). Twelve right-handed, healthy adults aged between 21 and 29 years (6 male, 6 female) underwent an ambiguity resolution task with 4 different conditions (dominant vs. non-dominant; dominant vs. distractor; non-dominant vs. distractor; distractor vs. distractor). After subtraction of the corresponding control task (distractor vs. distractor) we found significant activation especially in the thalamus and some parts of the basal ganglia (caudate nucleus, putamen). Our findings implicate a participation of the thalamus and other basal ganglia circuits in high level linguistic functions and match with theoretical considerations on this highly controversial topic. Subcortical neural circuits probably become activated when the language processing system cannot rely entirely on automatic mechanisms but has to recruit controlled processes as well. Furthermore, we found broad activation in the inferior parietal lobule, the prefrontal gyrus, pre-SMA and SMA and the cingulate cortex. This might reflect a strategic semantic search mechanism which probably can be illustrated with connectionist models of language processing. According to this, we hypothesize a neuroregulatory role for the thalamus and basal ganglia in regulating and monitoring the release of preformulated language segments for motor programming and semantic verification. According to our findings there is strong evidence, that especially the thalamus, the caudate nucleus, the cingulate cortex, the inferior parietal lobule and the prefrontal cortex are responsible for an accurate ambiguity resolution in the human brain.

Effects of reflector and crystal surface on the performance of a depth-encoding PET detector with dual-ended readout

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ren, Silin; Yang, Yongfeng, E-mail: yfyang@ucdavis.edu; Cherry, Simon R.

Purpose: Depth encoding detectors are required to improve the spatial resolution and spatial resolution uniformity of small animal positron emission tomography (PET) scanners, as well as dedicated breast and brain scanners. Depth of interaction (DOI) can be measured by using dual-ended readout of lutetium oxyorthosilicate (LSO) scintillator arrays with position-sensitive avalanche photodiodes. Inter-crystal reflectors and crystal surface treatments play important roles in determining the performance of dual-ended detectors. In this paper, the authors evaluated five LSO arrays made with three different intercrystal reflectors and with either polished or unpolished crystal surfaces. Methods: The crystal size in all arrays was 1.5more » mm, which is typical of the detector size used in small animal and dedicated breast scanners. The LSO arrays were measured with dual-ended readout and were compared in terms of flood histogram, energy resolution, and DOI resolution performance. Results: The four arrays using enhanced specular reflector (ESR) and Toray reflector provided similar quality flood histograms and the array using Crystal Wrap reflector gave the worst flood histogram. The two arrays using ESR reflector provided the best energy resolution and the array using Crystal Wrap reflector yielded the worst energy resolution. All arrays except the polished ESR array provided good DOI resolution ranging from 1.9 mm to 2.9 mm. DOI resolution improved as the gradient in light collection efficiency with depth (GLCED) increased. The geometric mean energies were also calculated for these dual-ended readout detectors as an alternative to the conventional summed total energy. It was shown that the geometric mean energy is advantageous in that it provides more uniform photopeak amplitude at different depths for arrays with high GLCED, and is beneficial in event selection by allowing a fixed energy window independent of depth. A new method of DOI calculation that improved the linearity of DOI ratio vs depth and simplifies the DOI calibration procedure also was developed and tested. Conclusions: The results of these studies provide useful guidance in selecting the proper reflectors and crystal surface treatments when LSO arrays are used for high-resolution PET applications in small animal scanners or dedicated breast and brain scanners.« less

Multi-Scale Computational Models for Electrical Brain Stimulation

PubMed Central

Seo, Hyeon; Jun, Sung C.

2017-01-01

Electrical brain stimulation (EBS) is an appealing method to treat neurological disorders. To achieve optimal stimulation effects and a better understanding of the underlying brain mechanisms, neuroscientists have proposed computational modeling studies for a decade. Recently, multi-scale models that combine a volume conductor head model and multi-compartmental models of cortical neurons have been developed to predict stimulation effects on the macroscopic and microscopic levels more precisely. As the need for better computational models continues to increase, we overview here recent multi-scale modeling studies; we focused on approaches that coupled a simplified or high-resolution volume conductor head model and multi-compartmental models of cortical neurons, and constructed realistic fiber models using diffusion tensor imaging (DTI). Further implications for achieving better precision in estimating cellular responses are discussed. PMID:29123476

Characterizing dynamic amplitude of low-frequency fluctuation and its relationship with dynamic functional connectivity: An application to schizophrenia.

PubMed

Fu, Zening; Tu, Yiheng; Di, Xin; Du, Yuhui; Pearlson, G D; Turner, J A; Biswal, Bharat B; Zhang, Zhiguo; Calhoun, V D

2017-09-20

The human brain is a highly dynamic system with non-stationary neural activity and rapidly-changing neural interaction. Resting-state dynamic functional connectivity (dFC) has been widely studied during recent years, and the emerging aberrant dFC patterns have been identified as important features of many mental disorders such as schizophrenia (SZ). However, only focusing on the time-varying patterns in FC is not enough, since the local neural activity itself (in contrast to the inter-connectivity) is also found to be highly fluctuating from research using high-temporal-resolution imaging techniques. Exploring the time-varying patterns in brain activity and their relationships with time-varying brain connectivity is important for advancing our understanding of the co-evolutionary property of brain network and the underlying mechanism of brain dynamics. In this study, we introduced a framework for characterizing time-varying brain activity and exploring its associations with time-varying brain connectivity, and applied this framework to a resting-state fMRI dataset including 151 SZ patients and 163 age- and gender matched healthy controls (HCs). In this framework, 48 brain regions were first identified as intrinsic connectivity networks (ICNs) using group independent component analysis (GICA). A sliding window approach was then adopted for the estimation of dynamic amplitude of low-frequency fluctuation (dALFF) and dFC, which were used to measure time-varying brain activity and time-varying brain connectivity respectively. The dALFF was further clustered into six reoccurring states by the k-means clustering method and the group difference in occurrences of dALFF states was explored. Lastly, correlation coefficients between dALFF and dFC were calculated and the group difference in these dALFF-dFC correlations was explored. Our results suggested that 1) ALFF of brain regions was highly fluctuating during the resting-state and such dynamic patterns are altered in SZ, 2) dALFF and dFC were correlated in time and their correlations are altered in SZ. The overall results support and expand prior work on abnormalities of brain activity, static FC (sFC) and dFC in SZ, and provide new evidence on aberrant time-varying brain activity and its associations with brain connectivity in SZ, which might underscore the disrupted brain cognitive functions in this mental disorder. Copyright © 2017 Elsevier Inc. All rights reserved.

Autoradiographic analysis of the in vivo distribution of 3H-imipramine and 3H-desipramine in brain: Comparison to in vitro binding patterns

DOE Office of Scientific and Technical Information (OSTI.GOV)

Duncan, G.E.; Paul, I.A.; Fassberg, J.B.

1991-03-01

Using high resolution autoradiographic techniques, the distribution of radioactivity in forebrain and brainstem was assessed after 4 injection of 3H-impramine or 3H-desipramine. Results were compared with regional binding of the drugs to brain sections in vitro. Similar topographic binding of 3H-imipramine and 3H-desipramine was observed in vitro among brain regions, except in the paraventricular nucleus of the hypothalamus and locus coeruleus, where binding was greater for 3H-desipramine. For both 3H-desipramine and 3H-imipramine, some brain regions that exhibited high binding in vitro also showed high accumulation after in vivo injection. However, certain regions that contained high densities of binding sites formore » the antidepressant drugs as measured by in vitro binding showed very low accumulation of radioactivity after in vivo treatment. Such regions included the dentate gyrus of the hippocampus, layer 1 of piriform cortex, caudate-putamen, pontine and midbrain central gray, and cerebellar granular layer. Compared to in vitro binding of the drugs, the distribution of imipramine and desipramine in vivo appears more anatomically selective. For imipramine, primary sites of action in vivo, as indicated by the topographic distribution in brain, appear to be the locus coeruleus, hippocampus, lateral septal nucleus, and amygdala. For desipramine, the greatest accumulation in vivo was found in the locus coeruleus, paraventricular nucleus of the hypothalamus, and anterior thalamic nuclei.« less

CT-based attenuation correction and resolution compensation for I-123 IMP brain SPECT normal database: a multicenter phantom study.

PubMed

Inui, Yoshitaka; Ichihara, Takashi; Uno, Masaki; Ishiguro, Masanobu; Ito, Kengo; Kato, Katsuhiko; Sakuma, Hajime; Okazawa, Hidehiko; Toyama, Hiroshi

2018-06-01

Statistical image analysis of brain SPECT images has improved diagnostic accuracy for brain disorders. However, the results of statistical analysis vary depending on the institution even when they use a common normal database (NDB), due to different intrinsic spatial resolutions or correction methods. The present study aimed to evaluate the correction of spatial resolution differences between equipment and examine the differences in skull bone attenuation to construct a common NDB for use in multicenter settings. The proposed acquisition and processing protocols were those routinely used at each participating center with additional triple energy window (TEW) scatter correction (SC) and computed tomography (CT) based attenuation correction (CTAC). A multicenter phantom study was conducted on six imaging systems in five centers, with either single photon emission computed tomography (SPECT) or SPECT/CT, and two brain phantoms. The gray/white matter I-123 activity ratio in the brain phantoms was 4, and they were enclosed in either an artificial adult male skull, 1300 Hounsfield units (HU), a female skull, 850 HU, or an acrylic cover. The cut-off frequency of the Butterworth filters was adjusted so that the spatial resolution was unified to a 17.9 mm full width at half maximum (FWHM), that of the lowest resolution system. The gray-to-white matter count ratios were measured from SPECT images and compared with the actual activity ratio. In addition, mean, standard deviation and coefficient of variation images were calculated after normalization and anatomical standardization to evaluate the variability of the NDB. The gray-to-white matter count ratio error without SC and attenuation correction (AC) was significantly larger for higher bone densities (p < 0.05). The count ratio error with TEW and CTAC was approximately 5% regardless of bone density. After adjustment of the spatial resolution in the SPECT images, the variability of the NDB decreased and was comparable to that of the NDB without correction. The proposed protocol showed potential for constructing an appropriate common NDB from SPECT images with SC, AC and spatial resolution compensation.

A robust multi-shot scan strategy for high-resolution diffusion weighted MRI enabled by multiplexed sensitivity-encoding (MUSE)

PubMed Central

Chen, Nan-kuei; Guidon, Arnaud; Chang, Hing-Chiu; Song, Allen W.

2013-01-01

Diffusion weighted magnetic resonance imaging (DWI) data have been mostly acquired with single-shot echo-planar imaging (EPI) to minimize motion induced artifacts. The spatial resolution, however, is inherently limited in single-shot EPI, even when the parallel imaging (usually at an acceleration factor of 2) is incorporated. Multi-shot acquisition strategies could potentially achieve higher spatial resolution and fidelity, but they are generally susceptible to motion-induced phase errors among excitations that are exacerbated by diffusion sensitizing gradients, rendering the reconstructed images unusable. It has been shown that shot-to-shot phase variations may be corrected using navigator echoes, but at the cost of imaging throughput. To address these challenges, a novel and robust multi-shot DWI technique, termed multiplexed sensitivity-encoding (MUSE), is developed here to reliably and inherently correct nonlinear shot-to-shot phase variations without the use of navigator echoes. The performance of the MUSE technique is confirmed experimentally in healthy adult volunteers on 3 Tesla MRI systems. This newly developed technique should prove highly valuable for mapping brain structures and connectivities at high spatial resolution for neuroscience studies. PMID:23370063

Decoding Multiple Sound Categories in the Human Temporal Cortex Using High Resolution fMRI

PubMed Central

Zhang, Fengqing; Wang, Ji-Ping; Kim, Jieun; Parrish, Todd; Wong, Patrick C. M.

2015-01-01

Perception of sound categories is an important aspect of auditory perception. The extent to which the brain’s representation of sound categories is encoded in specialized subregions or distributed across the auditory cortex remains unclear. Recent studies using multivariate pattern analysis (MVPA) of brain activations have provided important insights into how the brain decodes perceptual information. In the large existing literature on brain decoding using MVPA methods, relatively few studies have been conducted on multi-class categorization in the auditory domain. Here, we investigated the representation and processing of auditory categories within the human temporal cortex using high resolution fMRI and MVPA methods. More importantly, we considered decoding multiple sound categories simultaneously through multi-class support vector machine-recursive feature elimination (MSVM-RFE) as our MVPA tool. Results show that for all classifications the model MSVM-RFE was able to learn the functional relation between the multiple sound categories and the corresponding evoked spatial patterns and classify the unlabeled sound-evoked patterns significantly above chance. This indicates the feasibility of decoding multiple sound categories not only within but across subjects. However, the across-subject variation affects classification performance more than the within-subject variation, as the across-subject analysis has significantly lower classification accuracies. Sound category-selective brain maps were identified based on multi-class classification and revealed distributed patterns of brain activity in the superior temporal gyrus and the middle temporal gyrus. This is in accordance with previous studies, indicating that information in the spatially distributed patterns may reflect a more abstract perceptual level of representation of sound categories. Further, we show that the across-subject classification performance can be significantly improved by averaging the fMRI images over items, because the irrelevant variations between different items of the same sound category are reduced and in turn the proportion of signals relevant to sound categorization increases. PMID:25692885

High-resolution synchrotron radiation-based phase tomography of the healthy and epileptic brain

NASA Astrophysics Data System (ADS)

Bikis, Christos; Janz, Philipp; Schulz, Georg; Schweighauser, Gabriel; Hench, Jürgen; Thalmann, Peter; Deyhle, Hans; Chicherova, Natalia; Rack, Alexander; Khimchenko, Anna; Hieber, Simone E.; Mariani, Luigi; Haas, Carola A.; Müller, Bert

2016-10-01

Phase-contrast micro-tomography using synchrotron radiation has yielded superior soft tissue visualization down to the sub-cellular level. The isotropic spatial resolution down to about one micron is comparable to the one of histology. The methods, however, provide different physical quantities and are thus complementary, also allowing for the extension of histology into the third dimension. To prepare for cross-sectional animal studies on epilepsy, we have standardized the specimen's preparation and scanning procedure for mouse brains, so that subsequent histology remains entirely unaffected and scanning of all samples (n = 28) is possible in a realistic time frame. For that, we have scanned five healthy and epileptic mouse brains at the ID19 beamline, ESRF, Grenoble, France, using grating- and propagation-based phase contrast micro-tomography. The resulting datasets clearly show the cortex, ventricular system, thalamus, hypothalamus, and hippocampus. Our focus is on the latter, having planned kainate-induced epilepsy experiments. The cell density and organization in the dentate gyrus and Ammon's horn region were clearly visualized in control animals. This proof of principle was required to initiate experiment. The resulting three-dimensional data have been correlated to histology. The goal is a brain-wide quantification of cell death or structural reorganization associated with epilepsy as opposed to histology alone that represents small volumes of the total brain only. Thus, the proposed technique bears the potential to correlate the gold standard in analysis with independently obtained data sets. Such an achievement also fuels interest for other groups in neuroscience research to closely collaborate with experts in phase micro-tomography.

Parameter comparison of white matter diffusion tensor imaging (DTI) in rhesus macaques (Macaca mulatta)

PubMed Central

MO, Yin; CHAO, Fang; SONG, Ming; LIU, Ci-Rong; LIU, Hui-Lang; QIAN, Xi-Ying; ZHAO, Xu-Dong

2014-01-01

In this study, we analyzed diffusion tensor imaging (DTI) results of brain white matter in rhesus macaques (Macaca mulatta) with four different parameter settings and found that the sequence A (b=1 000 s/mm2, spatial resolution=1.25 mm×1.25 mm× 1.25 mm, numbers of direction=33, NSA=3) and B (b=800 s/mm2, spatial resolution=1.25 mm×1.25 mm×1.25 mm, numbers of direction=33, NSA=3) could accurately track coarse fibers. The fractional anisotropy (FA) derived from sequence C (b=1 000s/mm2, spatial resolution=0.55 mm×0.55 mm×2.5 mm, direction number=33, NSA=3) was too fuzzy to be used in tracking white matter fibers. By comparison, the high resolution and the FA with high contrast of gray matter and white matter derived from sequence D (b=800 s/mm2, spatial resolution=1.0 mm×1.0 mm ×1.0 mm, numbers of direction=33, NSA=3) qualified in its application in tracking both thick and thin fibers, making it an optimal DTI setting for rhesus macaques. PMID:24866488

The Brain Computer Interface Future: Time for a Strategy

DTIC Science & Technology

2013-02-14

electrophysiological activity can be measured by electroencepholography ( EEG ), electrocorticography (ECoG), magnetoencephalography (MEG), or signal activity...magnetic resonance imaging (MRI) or near infrared spectroscopy. Currently EEG is most the most widely used BCI interface due to high temporal...resolution, less user risk, and lower costs.12 EEG technology has been widely available for many decades but has significantly expanded as researchers

Hippocampal Structure and Human Cognition: Key Role of Spatial Processing and Evidence Supporting the Efficiency Hypothesis in Females

ERIC Educational Resources Information Center

Colom, Roberto; Stein, Jason L.; Rajagopalan, Priya; Martinez, Kenia; Hermel, David; Wang, Yalin; Alvarez-Linera, Juan; Burgaleta, Miguel; Quiroga, Ma. Angeles; Shih, Pei Chun; Thompson, Paul M.

2013-01-01

Here we apply a method for automated segmentation of the hippocampus in 3D high-resolution structural brain MRI scans. One hundred and four healthy young adults completed twenty one tasks measuring abstract, verbal, and spatial intelligence, along with working memory, executive control, attention, and processing speed. After permutation tests…

Laser Microdissection and Atmospheric Pressure Chemical Ionization Mass Spectrometry Coupled for Multimodal Imaging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lorenz, Matthias; Ovchinnikova, Olga S; Kertesz, Vilmos

2013-01-01

This paper describes the coupling of ambient laser ablation surface sampling, accomplished using a laser capture microdissection system, with atmospheric pressure chemical ionization mass spectrometry for high spatial resolution multimodal imaging. A commercial laser capture microdissection system was placed in close proximity to a modified ion source of a mass spectrometer designed to allow for sampling of laser ablated material via a transfer tube directly into the ionization region. Rhodamine 6G dye of red sharpie ink in a laser etched pattern as well as cholesterol and phosphatidylcholine in a cerebellum mouse brain thin tissue section were identified and imaged frommore » full scan mass spectra. A minimal spot diameter of 8 m was achieved using the 10X microscope cutting objective with a lateral oversampling pixel resolution of about 3.7 m. Distinguishing between features approximately 13 m apart in a cerebellum mouse brain thin tissue section was demonstrated in a multimodal fashion including co-registered optical and mass spectral chemical images.« less

A Hough transform global probabilistic approach to multiple-subject diffusion MRI tractography.

PubMed

Aganj, Iman; Lenglet, Christophe; Jahanshad, Neda; Yacoub, Essa; Harel, Noam; Thompson, Paul M; Sapiro, Guillermo

2011-08-01

A global probabilistic fiber tracking approach based on the voting process provided by the Hough transform is introduced in this work. The proposed framework tests candidate 3D curves in the volume, assigning to each one a score computed from the diffusion images, and then selects the curves with the highest scores as the potential anatomical connections. The algorithm avoids local minima by performing an exhaustive search at the desired resolution. The technique is easily extended to multiple subjects, considering a single representative volume where the registered high-angular resolution diffusion images (HARDI) from all the subjects are non-linearly combined, thereby obtaining population-representative tracts. The tractography algorithm is run only once for the multiple subjects, and no tract alignment is necessary. We present experimental results on HARDI volumes, ranging from simulated and 1.5T physical phantoms to 7T and 4T human brain and 7T monkey brain datasets. Copyright © 2011 Elsevier B.V. All rights reserved.

Characterization of a time-resolved non-contact scanning diffuse optical imaging system exploiting fast-gated single-photon avalanche diode detection

DOE Office of Scientific and Technical Information (OSTI.GOV)

Di Sieno, Laura, E-mail: laura.disieno@polimi.it; Dalla Mora, Alberto; Contini, Davide

2016-03-15

We present a system for non-contact time-resolved diffuse reflectance imaging, based on small source-detector distance and high dynamic range measurements utilizing a fast-gated single-photon avalanche diode. The system is suitable for imaging of diffusive media without any contact with the sample and with a spatial resolution of about 1 cm at 1 cm depth. In order to objectively assess its performances, we adopted two standardized protocols developed for time-domain brain imagers. The related tests included the recording of the instrument response function of the setup and the responsivity of its detection system. Moreover, by using liquid turbid phantoms with absorbingmore » inclusions, depth-dependent contrast and contrast-to-noise ratio as well as lateral spatial resolution were measured. To illustrate the potentialities of the novel approach, the characteristics of the non-contact system are discussed and compared to those of a fiber-based brain imager.« less

Linking Neurons to Network Function and Behavior by Two-Photon Holographic Optogenetics and Volumetric Imaging.

PubMed

Dal Maschio, Marco; Donovan, Joseph C; Helmbrecht, Thomas O; Baier, Herwig

2017-05-17

We introduce a flexible method for high-resolution interrogation of circuit function, which combines simultaneous 3D two-photon stimulation of multiple targeted neurons, volumetric functional imaging, and quantitative behavioral tracking. This integrated approach was applied to dissect how an ensemble of premotor neurons in the larval zebrafish brain drives a basic motor program, the bending of the tail. We developed an iterative photostimulation strategy to identify minimal subsets of channelrhodopsin (ChR2)-expressing neurons that are sufficient to initiate tail movements. At the same time, the induced network activity was recorded by multiplane GCaMP6 imaging across the brain. From this dataset, we computationally identified activity patterns associated with distinct components of the elicited behavior and characterized the contributions of individual neurons. Using photoactivatable GFP (paGFP), we extended our protocol to visualize single functionally identified neurons and reconstruct their morphologies. Together, this toolkit enables linking behavior to circuit activity with unprecedented resolution. Copyright © 2017 Elsevier Inc. All rights reserved.

Ultrasound-aided Multi-parametric Photoacoustic Microscopy of the Mouse Brain.

PubMed

Ning, Bo; Sun, Naidi; Cao, Rui; Chen, Ruimin; Kirk Shung, K; Hossack, John A; Lee, Jin-Moo; Zhou, Qifa; Hu, Song

2015-12-21

High-resolution quantitative imaging of cerebral oxygen metabolism in mice is crucial for understanding brain functions and formulating new strategies to treat neurological disorders, but remains a challenge. Here, we report on our newly developed ultrasound-aided multi-parametric photoacoustic microscopy (PAM), which enables simultaneous quantification of the total concentration of hemoglobin (CHb), the oxygen saturation of hemoglobin (sO2), and cerebral blood flow (CBF) at the microscopic level and through the intact mouse skull. The three-dimensional skull and vascular anatomies delineated by the dual-contrast (i.e., ultrasonic and photoacoustic) system provide important guidance for dynamically focused contour scan and vessel orientation-dependent correction of CBF, respectively. Moreover, bi-directional raster scan allows determining the direction of blood flow in individual vessels. Capable of imaging all three hemodynamic parameters at the same spatiotemporal scale, our ultrasound-aided PAM fills a critical gap in preclinical neuroimaging and lays the foundation for high-resolution mapping of the cerebral metabolic rate of oxygen (CMRO2)-a quantitative index of cerebral oxygen metabolism. This technical innovation is expected to shed new light on the mechanism and treatment of a broad spectrum of neurological disorders, including Alzheimer's disease and ischemic stroke.

Time reversal for ultrasonic transcranial surgery and echographic imaging

NASA Astrophysics Data System (ADS)

Tanter, Mickael; Aubry, Jean-Francois; Vignon, Francois; Fink, Mathias

2005-09-01

High-intensity focused ultrasound (HIFU) is able to induce non-invasively controlled and selective destruction of tissues by focusing ultrasonic beams within organs, analogous to a magnifying glass that concentrates enough sunlight to burn a hole in paper. The brain is an attractive organ in which to perform ultrasonic tissue ablation, but such an application has been hampered by the strong defocusing effect of the skull bone. Our group has been involved in this topic for several years, providing proofs of concept and proposing technological solutions to this problem. Thanks to a high-power time-reversal mirror, presented here are in vivo thermal lesions induced through the skull of 12 sheep. Thermal lesions were confirmed by T2-weighted magnetic resonance post-treatment images and histological examination. These results provide striking evidence that noninvasive ultrasound brain surgery is feasible. A recent approach for high-resolution brain ultrasonic imaging will also be discussed with a skull aberration correction technique based on twin arrays technology. The correction of transcranial ultrasonic images is implemented on a new generation of time-reversal mirrors relying on a fully programmable transmit and receive beamformer.

Magnetic resonance imaging-three-dimensional printing technology fabricates customized scaffolds for brain tissue engineering

PubMed Central

Fu, Feng; Qin, Zhe; Xu, Chao; Chen, Xu-yi; Li, Rui-xin; Wang, Li-na; Peng, Ding-wei; Sun, Hong-tao; Tu, Yue; Chen, Chong; Zhang, Sai; Zhao, Ming-liang; Li, Xiao-hong

2017-01-01

Conventional fabrication methods lack the ability to control both macro- and micro-structures of generated scaffolds. Three-dimensional printing is a solid free-form fabrication method that provides novel ways to create customized scaffolds with high precision and accuracy. In this study, an electrically controlled cortical impactor was used to induce randomized brain tissue defects. The overall shape of scaffolds was designed using rat-specific anatomical data obtained from magnetic resonance imaging, and the internal structure was created by computer-aided design. As the result of limitations arising from insufficient resolution of the manufacturing process, we magnified the size of the cavity model prototype five-fold to successfully fabricate customized collagen-chitosan scaffolds using three-dimensional printing. Results demonstrated that scaffolds have three-dimensional porous structures, high porosity, highly specific surface areas, pore connectivity and good internal characteristics. Neural stem cells co-cultured with scaffolds showed good viability, indicating good biocompatibility and biodegradability. This technique may be a promising new strategy for regenerating complex damaged brain tissues, and helps pave the way toward personalized medicine. PMID:28553343

Direct visualization of anatomic subfields within the superior aspect of the human lateral thalamus by MRI at 7T.

PubMed

Kanowski, M; Voges, J; Buentjen, L; Stadler, J; Heinze, H-J; Tempelmann, C

2014-09-01

The morphology of the human thalamus shows high interindividual variability. Therefore, direct visualization of landmarks within the thalamus is essential for an improved definition of electrode positions for deep brain stimulation. The aim of this study was to provide anatomic detail in the thalamus by using inversion recovery TSE imaging at 7T. The MR imaging protocol was optimized on 1 healthy subject to segment thalamic nuclei from one another. Final images, acquired with 0.5(2)-mm2 in-plane resolution and 3-mm section thickness, were compared with stereotactic brain atlases to assign visualized details to known anatomy. The robustness of the visualization of thalamic nuclei was assessed with 4 healthy subjects at lower image resolution. Thalamic subfields were successfully delineated in the dorsal aspect of the lateral thalamus. T1-weighting was essential. MR images had an appearance very similar to that of myelin-stained sections seen in brain atlases. Visualized intrathalamic structures were, among others, the lamella medialis, the external medullary lamina, the reticulatum thalami, the nucleus centre médian, the boundary between the nuclei dorso-oralis internus and externus, and the boundary between the nuclei dorso-oralis internus and zentrolateralis intermedius internus. Inversion recovery-prepared TSE imaging at 7T has a high potential to reveal fine anatomic detail in the thalamus, which may be helpful in enhancing the planning of stereotactic neurosurgery in the future. © 2014 by American Journal of Neuroradiology.

High-sensitivity brain SPECT system using cadmium telluride (CdTe) semiconductor detector and 4-pixel matched collimator.

PubMed

Suzuki, Atsuro; Takeuchi, Wataru; Ishitsu, Takafumi; Tsuchiya, Katsutoshi; Morimoto, Yuichi; Ueno, Yuichiro; Kobashi, Keiji; Kubo, Naoki; Shiga, Tohru; Tamaki, Nagara

2013-11-07

For high-sensitivity brain imaging, we have developed a two-head single-photon emission computed tomography (SPECT) system using a CdTe semiconductor detector and 4-pixel matched collimator (4-PMC). The term, '4-PMC' indicates that the collimator hole size is matched to a 2 × 2 array of detector pixels. By contrast, a 1-pixel matched collimator (1-PMC) is defined as a collimator whose hole size is matched to one detector pixel. The performance of the higher-sensitivity 4-PMC was experimentally compared with that of the 1-PMC. The sensitivities of the 1-PMC and 4-PMC were 70 cps/MBq/head and 220 cps/MBq/head, respectively. The SPECT system using the 4-PMC provides superior image resolution in cold and hot rods phantom with the same activity and scan time to that of the 1-PMC. In addition, with half the usual scan time the 4-PMC provides comparable image quality to that of the 1-PMC. Furthermore, (99m)Tc-ECD brain perfusion images of healthy volunteers obtained using the 4-PMC demonstrated acceptable image quality for clinical diagnosis. In conclusion, our CdTe SPECT system equipped with the higher-sensitivity 4-PMC can provide better spatial resolution than the 1-PMC either in half the imaging time with the same administered activity, or alternatively, in the same imaging time with half the activity.

Music-Evoked Emotions—Current Studies

PubMed Central

Schaefer, Hans-Eckhardt

2017-01-01

The present study is focused on a review of the current state of investigating music-evoked emotions experimentally, theoretically and with respect to their therapeutic potentials. After a concise historical overview and a schematic of the hearing mechanisms, experimental studies on music listeners and on music performers are discussed, starting with the presentation of characteristic musical stimuli and the basic features of tomographic imaging of emotional activation in the brain, such as functional magnetic resonance imaging (fMRI) and positron emission tomography (PET), which offer high spatial resolution in the millimeter range. The progress in correlating activation imaging in the brain to the psychological understanding of music-evoked emotion is demonstrated and some prospects for future research are outlined. Research in psychoneuroendocrinology and molecular markers is reviewed in the context of music-evoked emotions and the results indicate that the research in this area should be intensified. An assessment of studies involving measuring techniques with high temporal resolution down to the 10 ms range, as, e.g., electroencephalography (EEG), event-related brain potentials (ERP), magnetoencephalography (MEG), skin conductance response (SCR), finger temperature, and goose bump development (piloerection) can yield information on the dynamics and kinetics of emotion. Genetic investigations reviewed suggest the heredity transmission of a predilection for music. Theoretical approaches to musical emotion are directed to a unified model for experimental neurological evidence and aesthetic judgment. Finally, the reports on musical therapy are briefly outlined. The study concludes with an outlook on emerging technologies and future research fields. PMID:29225563

Tissue Localization of Glycosphingolipid Accumulation in a Gaucher Disease Mouse Brain by LC-ESI-MS/MS and High-Resolution MALDI Imaging Mass Spectrometry.

PubMed

Jones, E Ellen; Zhang, Wujuan; Zhao, Xueheng; Quiason, Cristine; Dale, Stephanie; Shahidi-Latham, Sheerin; Grabowski, Gregory A; Setchell, Kenneth D R; Drake, Richard R; Sun, Ying

2017-12-01

To better understand regional brain glycosphingolipid (GSL) accumulation in Gaucher disease (GD) and its relationship to neuropathology, a feasibility study using mass spectrometry and immunohistochemistry was conducted using brains derived from a GD mouse model (4L/PS/NA) homozygous for a mutant GCase (V394L [4L]) and expressing a prosaposin hypomorphic (PS-NA) transgene. Whole brains from GD and control animals were collected using one hemisphere for MALDI FTICR IMS analysis and the other for quantitation by LC-ESI-MS/MS. MALDI IMS detected several HexCers across the brains. Comparison with the brain hematoxylin and eosin (H&E) revealed differential signal distributions in the midbrain, brain stem, and CB of the GD brain versus the control. Quantitation of serial brain sections with LC-ESI-MS/MS supported the imaging results, finding the overall HexCer levels in the 4L/PS-NA brains to be four times higher than the control. LC-ESI-MS/MS also confirmed that the elevated hexosyl isomers were glucosylceramides rather than galactosylceramides. MALDI imaging also detected differential analyte distributions of lactosylceramide species and gangliosides in the 4L/PS-NA brain, which was validated by LC-ESI-MS/MS. Immunohistochemistry revealed regional inflammation, altered autophagy, and defective protein degradation correlating with regions of GSL accumulation, suggesting that specific GSLs may have distinct neuropathological effects.

Hierarchical organization of brain functional networks during visual tasks.

PubMed

Zhuo, Zhao; Cai, Shi-Min; Fu, Zhong-Qian; Zhang, Jie

2011-09-01

The functional network of the brain is known to demonstrate modular structure over different hierarchical scales. In this paper, we systematically investigated the hierarchical modular organizations of the brain functional networks that are derived from the extent of phase synchronization among high-resolution EEG time series during a visual task. In particular, we compare the modular structure of the functional network from EEG channels with that of the anatomical parcellation of the brain cortex. Our results show that the modular architectures of brain functional networks correspond well to those from the anatomical structures over different levels of hierarchy. Most importantly, we find that the consistency between the modular structures of the functional network and the anatomical network becomes more pronounced in terms of vision, sensory, vision-temporal, motor cortices during the visual task, which implies that the strong modularity in these areas forms the functional basis for the visual task. The structure-function relationship further reveals that the phase synchronization of EEG time series in the same anatomical group is much stronger than that of EEG time series from different anatomical groups during the task and that the hierarchical organization of functional brain network may be a consequence of functional segmentation of the brain cortex.

Low-Cost High-Performance MRI

NASA Astrophysics Data System (ADS)

Sarracanie, Mathieu; Lapierre, Cristen D.; Salameh, Najat; Waddington, David E. J.; Witzel, Thomas; Rosen, Matthew S.

2015-10-01

Magnetic Resonance Imaging (MRI) is unparalleled in its ability to visualize anatomical structure and function non-invasively with high spatial and temporal resolution. Yet to overcome the low sensitivity inherent in inductive detection of weakly polarized nuclear spins, the vast majority of clinical MRI scanners employ superconducting magnets producing very high magnetic fields. Commonly found at 1.5-3 tesla (T), these powerful magnets are massive and have very strict infrastructure demands that preclude operation in many environments. MRI scanners are costly to purchase, site, and maintain, with the purchase price approaching $1 M per tesla (T) of magnetic field. We present here a remarkably simple, non-cryogenic approach to high-performance human MRI at ultra-low magnetic field, whereby modern under-sampling strategies are combined with fully-refocused dynamic spin control using steady-state free precession techniques. At 6.5 mT (more than 450 times lower than clinical MRI scanners) we demonstrate (2.5 × 3.5 × 8.5) mm3 imaging resolution in the living human brain using a simple, open-geometry electromagnet, with 3D image acquisition over the entire brain in 6 minutes. We contend that these practical ultra-low magnetic field implementations of MRI (<10 mT) will complement traditional MRI, providing clinically relevant images and setting new standards for affordable (<$50,000) and robust portable devices.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xu, C. Shan; Hayworth, Kenneth J.; Lu, Zhiyuan

Focused Ion Beam Scanning Electron Microscopy (FIB-SEM) can automatically generate 3D images with superior z-axis resolution, yielding data that needs minimal image registration and related post-processing. Obstacles blocking wider adoption of FIB-SEM include slow imaging speed and lack of long-term system stability, which caps the maximum possible acquisition volume. Here, we present techniques that accelerate image acquisition while greatly improving FIB-SEM reliability, allowing the system to operate for months and generating continuously imaged volumes > 10 6 ?m 3 . These volumes are large enough for connectomics, where the excellent z resolution can help in tracing of small neuronal processesmore » and accelerate the tedious and time-consuming human proofreading effort. Even higher resolution can be achieved on smaller volumes. We present example data sets from mammalian neural tissue, Drosophila brain, and Chlamydomonas reinhardtii to illustrate the power of this novel high-resolution technique to address questions in both connectomics and cell biology.« less

Enhanced FIB-SEM systems for large-volume 3D imaging.

PubMed

Xu, C Shan; Hayworth, Kenneth J; Lu, Zhiyuan; Grob, Patricia; Hassan, Ahmed M; García-Cerdán, José G; Niyogi, Krishna K; Nogales, Eva; Weinberg, Richard J; Hess, Harald F

2017-05-13

Focused Ion Beam Scanning Electron Microscopy (FIB-SEM) can automatically generate 3D images with superior z-axis resolution, yielding data that needs minimal image registration and related post-processing. Obstacles blocking wider adoption of FIB-SEM include slow imaging speed and lack of long-term system stability, which caps the maximum possible acquisition volume. Here, we present techniques that accelerate image acquisition while greatly improving FIB-SEM reliability, allowing the system to operate for months and generating continuously imaged volumes > 10 6 µm 3 . These volumes are large enough for connectomics, where the excellent z resolution can help in tracing of small neuronal processes and accelerate the tedious and time-consuming human proofreading effort. Even higher resolution can be achieved on smaller volumes. We present example data sets from mammalian neural tissue, Drosophila brain, and Chlamydomonas reinhardtii to illustrate the power of this novel high-resolution technique to address questions in both connectomics and cell biology.