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Jelescu IO, Grussu F, Ianus A, Hansen B, Barrett RLC, Aggarwal M, Michielse S, Nasrallah F, Syeda W, Wang N, Veraart J, Roebroeck A, Bagdasarian AF, Eichner C, Sepehrband F, Zimmermann J, Soustelle L, Bowman C, Tendler BC, Hertanu A, Jeurissen B, Verhoye M, Frydman L, van de Looij Y, Hike D, Dunn JF, Miller K, Landman BA, Shemesh N, Anderson A, McKinnon E, Farquharson S, Dell'Acqua F, Pierpaoli C, Drobnjak I, Leemans A, Harkins KD, Descoteaux M, Xu D, Huang H, Santin MD, Grant SC, Obenaus A, Kim GS, Wu D, Le Bihan D, Blackband SJ, Ciobanu L, Fieremans E, Bai R, Leergaard TB, Zhang J, Dyrby TB, Johnson GA, Cohen‐Adad J, Budde MD, Schilling KG. Considerations and recommendations from the ISMRM diffusion study group for preclinical diffusion MRI: Part 1: In vivo small-animal imaging. Magn Reson Med 2025; 93:2507-2534. [PMID: 40008568 PMCID: PMC11971505 DOI: 10.1002/mrm.30429] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2024] [Revised: 12/19/2024] [Accepted: 12/26/2024] [Indexed: 02/27/2025]
Abstract
Small-animal diffusion MRI (dMRI) has been used for methodological development and validation, characterizing the biological basis of diffusion phenomena, and comparative anatomy. The steps from animal setup and monitoring, to acquisition, analysis, and interpretation are complex, with many decisions that may ultimately affect what questions can be answered using the resultant data. This work aims to present selected considerations and recommendations from the diffusion community on best practices for preclinical dMRI of in vivo animals. We describe the general considerations and foundational knowledge that must be considered when designing experiments. We briefly describe differences in animal species and disease models and discuss why some may be more or less appropriate for different studies. We, then, give recommendations for in vivo acquisition protocols, including decisions on hardware, animal preparation, and imaging sequences, followed by advice for data processing including preprocessing, model-fitting, and tractography. Finally, we provide an online resource that lists publicly available preclinical dMRI datasets and software packages to promote responsible and reproducible research. In each section, we attempt to provide guides and recommendations, but also highlight areas for which no guidelines exist (and why), and where future work should focus. Although we mainly cover the central nervous system (on which most preclinical dMRI studies are focused), we also provide, where possible and applicable, recommendations for other organs of interest. An overarching goal is to enhance the rigor and reproducibility of small animal dMRI acquisitions and analyses, and thereby advance biomedical knowledge.
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Affiliation(s)
- Ileana O. Jelescu
- Department of RadiologyLausanne University Hospital and University of LausanneLausanneSwitzerland
- CIBM Center for Biomedical ImagingEcole Polytechnique Fédérale de LausanneLausanneSwitzerland
| | - Francesco Grussu
- Radiomics GroupVall d'Hebron Institute of Oncology, Vall d'Hebron Barcelona Hospital CampusBarcelonaSpain
- Queen Square MS Centre, Queen Square Institute of Neurology, Faculty of Brain SciencesUniversity College LondonLondonUK
| | - Andrada Ianus
- Champalimaud ResearchChampalimaud FoundationLisbonPortugal
- School of Biomedical Engineering and Imaging SciencesKing's College LondonLondonUK
| | - Brian Hansen
- Center of Functionally Integrative NeuroscienceAarhus UniversityAarhusDenmark
| | - Rachel L. C. Barrett
- Department of NeuroimagingInstitute of Psychiatry, Psychology and Neuroscience, King's College LondonLondonUK
- NatBrainLab, Department of Forensics and Neurodevelopmental SciencesInstitute of Psychiatry, Psychology and Neuroscience, King's College LondonLondonUK
| | - Manisha Aggarwal
- Russell H. Morgan Department of Radiology and Radiological ScienceJohns Hopkins University School of MedicineBaltimoreMarylandUSA
| | - Stijn Michielse
- Department of Neurosurgery, School for Mental Health and Neuroscience (MHeNS)Maastricht University Medical CenterMaastrichtThe Netherlands
| | - Fatima Nasrallah
- The Queensland Brain InstituteThe University of QueenslandSt LuciaQueenslandAustralia
| | - Warda Syeda
- Melbourne Neuropsychiatry CentreThe University of MelbourneParkvilleVictoriaAustralia
| | - Nian Wang
- Department of Radiology and Imaging SciencesIndiana UniversityBloomingtonIndianaUSA
- Stark Neurosciences Research InstituteIndiana University School of MedicineBloomingtonIndianaUSA
| | - Jelle Veraart
- Center for Biomedical ImagingNYU Grossman School of MedicineNew YorkNew YorkUSA
| | - Alard Roebroeck
- Faculty of psychology and NeuroscienceMaastricht UniversityMaastrichtThe Netherlands
| | - Andrew F. Bagdasarian
- Department of Chemical and Biomedical Engineering, FAMU‐FSU College of EngineeringFlorida State UniversityTallahasseeFloridaUSA
- Center for Interdisciplinary Magnetic ResonanceNational HIgh Magnetic Field LaboratoryTallahasseeFloridaUSA
| | - Cornelius Eichner
- Department of NeuropsychologyMax Planck Institute for Human Cognitive and Brain SciencesLeipzigGermany
| | - Farshid Sepehrband
- USC Stevens Neuroimaging and Informatics Institute, Keck School of Medicine of USCUniversity of Southern CaliforniaCaliforniaLos AngelesUSA
| | - Jan Zimmermann
- Department of Neuroscience, Center for Magnetic Resonance ResearchUniversity of MinnesotaMinneapolisMinnesotaUSA
| | | | - Christien Bowman
- Bio‐Imaging Lab, Faculty of Pharmaceutical, Biomedical and Veterinary SciencesUniversity of AntwerpAntwerpBelgium
- μNEURO Research Centre of ExcellenceUniversity of AntwerpAntwerpBelgium
| | - Benjamin C. Tendler
- Wellcome Centre for Integrative Neuroimaging, FMRIB, Nuffield Department of Clinical NeurosciencesUniversity of OxfordOxfordUK
| | - Andreea Hertanu
- Department of RadiologyLausanne University Hospital and University of LausanneLausanneSwitzerland
| | - Ben Jeurissen
- imec Vision Lab, Department of PhysicsUniversity of AntwerpAntwerpenBelgium
- Lab for Equilibrium Investigations and Aerospace, Department of PhysicsUniversity of AntwerpAntwerpenBelgium
| | - Marleen Verhoye
- Bio‐Imaging Lab, Faculty of Pharmaceutical, Biomedical and Veterinary SciencesUniversity of AntwerpAntwerpBelgium
- μNEURO Research Centre of ExcellenceUniversity of AntwerpAntwerpBelgium
| | - Lucio Frydman
- Department of Chemical and Biological PhysicsWeizmann Institute of ScienceRehovotIsrael
| | - Yohan van de Looij
- Division of Child Development and Growth, Department of Pediatrics, Gynaecology and Obstetrics, School of MedicineUniversité de GenèveGenèveSwitzerland
| | - David Hike
- Department of Chemical and Biomedical Engineering, FAMU‐FSU College of EngineeringFlorida State UniversityTallahasseeFloridaUSA
- Center for Interdisciplinary Magnetic ResonanceNational HIgh Magnetic Field LaboratoryTallahasseeFloridaUSA
| | - Jeff F. Dunn
- Department of Radiology, Cumming School of MedicineUniversity of CalgaryCalgaryAlbertaCanada
- Hotchkiss Brain Institute, Cumming School of MedicineUniversity of CalgaryCalgaryAlbertaCanada
- Alberta Children's Hospital Research Institute, Cumming School of MedicineUniversity of CalgaryCalgaryAlbertaCanada
| | - Karla Miller
- FMRIB Centre, Wellcome Centre for Integrative Neuroimaging, Nuffield Department of Clinical NeurosciencesUniversity of OxfordOxfordUK
| | - Bennett A. Landman
- Department of Electrical and Computer EngineeringVanderbilt UniversityNashvilleTennesseeUSA
| | - Noam Shemesh
- Champalimaud ResearchChampalimaud FoundationLisbonPortugal
| | - Adam Anderson
- Vanderbilt University Institute of Imaging ScienceVanderbilt UniversityNashvilleTennesseeUSA
- Department of Radiology and Radiological SciencesVanderbilt University Medical CenterNashvilleTennesseeUSA
| | - Emilie McKinnon
- Medical University of South CarolinaCharlestonSouth CarolinaUSA
| | - Shawna Farquharson
- National Imaging FacilityThe University of QueenslandBrisbaneQueenslandAustralia
| | - Flavio Dell'Acqua
- Department of Forensic and Neurodevelopmental SciencesKing's College LondonLondonUK
| | - Carlo Pierpaoli
- Laboratory on Quantitative Medical imaging, NIBIBNational Institutes of HealthBethesdaMarylandUSA
| | - Ivana Drobnjak
- Department of Computer ScienceUniversity College LondonLondonUK
| | - Alexander Leemans
- PROVIDI Lab, Image Sciences InstituteUniversity Medical Center UtrechtUtrechtThe Netherlands
| | - Kevin D. Harkins
- Vanderbilt University Institute of Imaging ScienceVanderbilt UniversityNashvilleTennesseeUSA
- Radiology and Radiological SciencesVanderbilt University Medical CenterNashvilleTennesseeUSA
- Biomedical EngineeringVanderbilt UniversityNashvilleTennesseeUSA
| | - Maxime Descoteaux
- Sherbrooke Connectivity Imaing Lab (SCIL), Computer Science DepartmentUniversité de SherbrookeSherbrookeQuebecCanada
- Imeka SolutionsSherbrookeQuebecCanada
| | - Duan Xu
- Department of Radiology and Biomedical ImagingUniversity of California San FranciscoSan FranciscoCaliforniaUSA
| | - Hao Huang
- Department of Radiology, Perelman School of MedicineUniversity of PennsylvaniaPhiladelphiaPennsylvaniaUSA
- Department of RadiologyChildren's Hospital of PhiladelphiaPhiladelphiaPennsylvaniaUSA
| | - Mathieu D. Santin
- Centre for NeuroImaging Research (CENIR), Inserm U 1127, CNRS UMR 7225Sorbonne UniversitéParisFrance
- Paris Brain InstituteParisFrance
| | - Samuel C. Grant
- Department of Chemical and Biomedical Engineering, FAMU‐FSU College of EngineeringFlorida State UniversityTallahasseeFloridaUSA
- Center for Interdisciplinary Magnetic ResonanceNational HIgh Magnetic Field LaboratoryTallahasseeFloridaUSA
| | - Andre Obenaus
- Division of Biomedical SciencesUniversity of California RiversideRiversideCaliforniaUSA
- Preclinical and Translational Imaging CenterUniversity of California IrvineIrvineCaliforniaUSA
| | - Gene S. Kim
- Department of RadiologyWeill Cornell Medical CollegeNew YorkNew YorkUSA
| | - Dan Wu
- Key Laboratory for Biomedical Engineering of Ministry of Education, College of Biomedical Engineering and Instrument ScienceZhejiang UniversityHangzhouChina
| | - Denis Le Bihan
- CEA, DRF, JOLIOT, NeuroSpinGif‐sur‐YvetteFrance
- Université Paris‐SaclayGif‐sur‐YvetteFrance
| | - Stephen J. Blackband
- Department of NeuroscienceUniversity of FloridaGainesvilleFloridaUSA
- McKnight Brain InstituteUniversity of FloridaGainesvilleFloridaUSA
- National High Magnetic Field LaboratoryTallahasseeFloridaUSA
| | - Luisa Ciobanu
- NeuroSpin, UMR CEA/CNRS 9027Paris‐Saclay UniversityGif‐sur‐YvetteFrance
| | - Els Fieremans
- Department of RadiologyNew York University Grossman School of MedicineNew YorkNew YorkUSA
| | - Ruiliang Bai
- Interdisciplinary Institute of Neuroscience and Technology, School of MedicineZhejiang UniversityHangzhouChina
- Frontier Center of Brain Science and Brain‐Machine IntegrationZhejiang UniversityZhejiangChina
| | - Trygve B. Leergaard
- Department of Molecular Biology, Institute of Basic Medical SciencesUniversity of OsloOsloNorway
| | - Jiangyang Zhang
- Department of RadiologyNew York University School of MedicineNew YorkNew YorkUSA
| | - Tim B. Dyrby
- Danish Research Centre for Magnetic ResonanceCentre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Amager and HvidovreHvidovreDenmark
- Department of Applied Mathematics and Computer ScienceTechnical University of DenmarkKongens LyngbyDenmark
| | - G. Allan Johnson
- Duke Center for In Vivo Microscopy, Department of RadiologyDuke UniversityDurhamNorth CarolinaUSA
- Department of Biomedical EngineeringDuke UniversityDurhamNorth CarolinaUSA
| | - Julien Cohen‐Adad
- NeuroPoly Lab, Institute of Biomedical EngineeringPolytechnique MontrealMontrealQuebecCanada
- Functional Neuroimaging Unit, CRIUGMUniversity of MontrealMontrealQuebecCanada
- Mila ‐ Quebec AI InstituteMontrealQuebecCanada
| | - Matthew D. Budde
- Department of NeurosurgeryMedical College of WisconsinMilwaukeeWisconsinUSA
- Clement J Zablocki VA Medical CenterMilwaukeeWisconsinUSA
| | - Kurt G. Schilling
- Vanderbilt University Institute of Imaging ScienceVanderbilt UniversityNashvilleTennesseeUSA
- Radiology and Radiological SciencesVanderbilt University Medical CenterNashvilleTennesseeUSA
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Inglis FM, Taylor PA, Andrews EF, Pascalau R, Voss HU, Glen DR, Johnson PJ. A diffusion tensor imaging white matter atlas of the domestic canine brain. IMAGING NEUROSCIENCE (CAMBRIDGE, MASS.) 2024; 2:1-21. [PMID: 39301427 PMCID: PMC11409835 DOI: 10.1162/imag_a_00276] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 02/17/2024] [Revised: 07/02/2024] [Accepted: 07/23/2024] [Indexed: 09/22/2024]
Abstract
There is increasing reliance on magnetic resonance imaging (MRI) techniques in both research and clinical settings. However, few standardized methods exist to permit comparative studies of brain pathology and function. To help facilitate these studies, we have created a detailed, MRI-based white matter atlas of the canine brain using diffusion tensor imaging. This technique, which relies on the movement properties of water, permits the creation of a three-dimensional diffusivity map of white matter brain regions that can be used to predict major axonal tracts. To generate an atlas of white matter tracts, thirty neurologically and clinically normal dogs underwent MRI imaging under anesthesia. High-resolution, three-dimensional T1-weighted sequences were collected and averaged to create a population average template. Diffusion-weighted imaging sequences were collected and used to generate diffusivity maps, which were then registered to the T1-weighted template. Using these diffusivity maps, individual white matter tracts-including association, projection, commissural, brainstem, olfactory, and cerebellar tracts-were identified with reference to previous canine brain atlas sources. To enable the use of this atlas, we created downloadable overlay files for each white matter tract identified using manual segmentation software. In addition, using diffusion tensor imaging tractography, we created tract files to delineate major projection pathways. This comprehensive white matter atlas serves as a standard reference to aid in the interpretation of quantitative changes in brain structure and function in clinical and research settings.
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Affiliation(s)
- Fiona M Inglis
- Cornell College of Veterinary Medicine, Department of Clinical Sciences, Cornell University, Ithaca, NY, United States
| | - Paul A Taylor
- Scientific and Statistical Computing Core, National Institute of Mental Health, Bethesda, MD, United States
| | - Erica F Andrews
- Cornell College of Veterinary Medicine, Department of Clinical Sciences, Cornell University, Ithaca, NY, United States
| | - Raluca Pascalau
- Faculty of Medicine, "Iuliu Hatieganu" University of Medicine and Pharmacy, Cluj-Napoca, Romania
| | - Henning U Voss
- Cornell Magnetic Resonance Imaging Facility, College of Human Ecology, Cornell University, Cornell, Ithaca, NY, United States
| | - Daniel R Glen
- Scientific and Statistical Computing Core, National Institute of Mental Health, Bethesda, MD, United States
| | - Philippa J Johnson
- Cornell College of Veterinary Medicine, Department of Clinical Sciences, Cornell University, Ithaca, NY, United States
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Liachenko S, Sarkar S. In vivo mapping of rat brain partial white matter content using hexachlorophene-induced neurotoxicity model. Brain Res 2024; 1830:148811. [PMID: 38365131 DOI: 10.1016/j.brainres.2024.148811] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2023] [Revised: 01/26/2024] [Accepted: 02/13/2024] [Indexed: 02/18/2024]
Abstract
Segmentation of the white matter in MRI scans of the rat brain presents a significant challenge due to the low contrast. Existing anatomical reference maps of rat brain are usually constructed from fixed tissue, which may suffer from geometrical distortions due to fixation/processing. To significantly increase the in vivo contrast between white and gray matter in the rat brain we used a known neurotoxicant hexachlorophene, which produces selective white matter damage. This model was used to map white matter in the rat brain and estimate the partial white matter content in any given imaging voxel. Hexachlorophene was administered to rats at a dose of 30 mg/kg orally once a day over five consecutive days. A significant white matter changes were observed using quantitative T2 maps, from which the partial white matter content throughout the whole rat brain was derived. Several assumptions were made: hexachlorophene affects T2 relaxation only in the white matter; T2 of gray matter is relatively uniform in the brain; apparent T2 value in a given voxel is a combination of T2s from white and gray matter portions of that voxel, hexachlorophene affects nearly 100 % of white matter. The partial white matter map of the rat brain was constructed with the resolution of 0.2 × 0.2 × 1.0 mm per voxel. This map could be adjusted for segmentation of the brain tissue with preset threshold of the white matter content, or to establish the tissue composition in any region of interest among other applications.
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Affiliation(s)
- Serguei Liachenko
- Division of Neurotoxicology, National Center for Toxicological Research, US Food and Drug Administration, Jefferson, AR, United States.
| | - Sumit Sarkar
- Division of Neurotoxicology, National Center for Toxicological Research, US Food and Drug Administration, Jefferson, AR, United States
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Ma X, Xing Y, Zhai R, Du Y, Yan H. Development and advancements in rodent MRI-based brain atlases. Heliyon 2024; 10:e27421. [PMID: 38510053 PMCID: PMC10950579 DOI: 10.1016/j.heliyon.2024.e27421] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2023] [Revised: 02/15/2024] [Accepted: 02/28/2024] [Indexed: 03/22/2024] Open
Abstract
Rodents, particularly mice and rats, are extensively utilized in fundamental neuroscience research. Brain atlases have played a pivotal role in this field, evolving from traditional printed histology atlases to digital atlases incorporating diverse imaging datasets. Magnetic resonance imaging (MRI)-based brain atlases, also known as brain maps, have been employed in specific studies. However, the existence of numerous versions of MRI-based brain atlases has impeded their standardized application and widespread use, despite the consensus within the academic community regarding their significance in mice and rats. Furthermore, there is a dearth of comprehensive and systematic reviews on MRI-based brain atlases for rodents. This review aims to bridge this gap by providing a comprehensive overview of the advancements in MRI-based brain atlases for rodents, with a specific focus on mice and rats. It seeks to explore the advantages and disadvantages of histologically printed brain atlases in comparison to MRI brain atlases, delineate the standardized methods for creating MRI brain atlases, and summarize their primary applications in neuroscience research. Additionally, this review aims to assist researchers in selecting appropriate versions of MRI brain atlases for their studies or refining existing MRI brain atlas resources, thereby facilitating the development and widespread adoption of standardized MRI-based brain atlases in rodents.
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Affiliation(s)
- Xiaoyi Ma
- Department of Geriatrics, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510080, China
| | - Yao Xing
- School of Information Science and Technology, Fudan University, Shanghai, 200433, China
- Wuhan United Imaging Life Science Instrument Co., Ltd., Wuhan, 430071, China
| | - Renkuan Zhai
- Wuhan United Imaging Life Science Instrument Co., Ltd., Wuhan, 430071, China
| | - Yingying Du
- Wuhan United Imaging Life Science Instrument Co., Ltd., Wuhan, 430071, China
| | - Huanhuan Yan
- Shenzhen United Imaging Research Institute of Innovative Medical Equipment, Shenzhen, 518048, China
- Paul C. Lauterbur Research Center for Biomedical Imaging, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China
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Filipiak P, Sajitha TA, Shepherd TM, Clarke K, Goldman H, Placantonakis DG, Zhang J, Chan KC, Boada FE, Baete SH. Improved reconstruction of crossing fibers in the mouse optic pathways with orientation distribution function fingerprinting. Magn Reson Med 2024; 91:1075-1086. [PMID: 37927121 PMCID: PMC11572703 DOI: 10.1002/mrm.29911] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2023] [Revised: 10/10/2023] [Accepted: 10/14/2023] [Indexed: 11/07/2023]
Abstract
PURPOSE The accuracy of diffusion MRI tractography reconstruction decreases in the white matter regions with crossing fibers. The optic pathways in rodents provide a challenging structure to test new diffusion tractography approaches because of the small crossing volume within the optic chiasm and the unbalanced 9:1 proportion between the contra- and ipsilateral neural projections from the retina to the lateral geniculate nucleus, respectively. METHODS Common approaches based on Orientation Distribution Function (ODF) peak finding or statistical inference were compared qualitatively and quantitatively to ODF Fingerprinting (ODF-FP) for reconstruction of crossing fibers within the optic chiasm using in vivo diffusion MRI (n = 18 $$ n=18 $$ healthy C57BL/6 mice). Manganese-Enhanced MRI (MEMRI) was obtained after intravitreal injection of manganese chloride and used as a reference standard for the optic pathway anatomy. RESULTS ODF-FP outperformed by over 100% all the tested methods in terms of the ratios between the contra- and ipsilateral segments of the reconstructed optic pathways as well as the spatial overlap between tractography and MEMRI. CONCLUSION In this challenging model system, ODF-Fingerprinting reduced uncertainty of diffusion tractography for complex structural formations of fiber bundles.
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Affiliation(s)
- Patryk Filipiak
- Center for Advanced Imaging Innovation and Research (CAIR), Department of Radiology, NYU Langone Health, New York, NY, USA
| | | | - Timothy M. Shepherd
- Center for Advanced Imaging Innovation and Research (CAIR), Department of Radiology, NYU Langone Health, New York, NY, USA
| | - Kamri Clarke
- Center for Advanced Imaging Innovation and Research (CAIR), Department of Radiology, NYU Langone Health, New York, NY, USA
| | - Hannah Goldman
- Center for Advanced Imaging Innovation and Research (CAIR), Department of Radiology, NYU Langone Health, New York, NY, USA
| | - Dimitris G. Placantonakis
- Department of Neurosurgery, Perlmutter Cancer Center, Neuroscience Institute, Kimmel Center for Stem Cell Biology, NYU Langone Health, New York, NY, USA
| | - Jiangyang Zhang
- Center for Advanced Imaging Innovation and Research (CAIR), Department of Radiology, NYU Langone Health, New York, NY, USA
| | - Kevin C. Chan
- Center for Advanced Imaging Innovation and Research (CAIR), Department of Radiology, NYU Langone Health, New York, NY, USA
- Department of Ophthalmology, NYU Langone Health, New York, NY, USA
| | - Fernando E. Boada
- Radiological Sciences Laboratory and Molecular Imaging Program at Stanford, Department of Radiology, Stanford University, Stanford, CA, USA
| | - Steven H. Baete
- Center for Advanced Imaging Innovation and Research (CAIR), Department of Radiology, NYU Langone Health, New York, NY, USA
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Strain MM, Tongkhuya S, Wienandt N, Alsadoon F, Chavez R, Daniels J, Garza T, Trevino AV, Wells K, Stark T, Clifford J, Sosanya NM. Exploring combat stress exposure effects on burn pain in a female rodent model. BMC Neurosci 2022; 23:73. [PMID: 36474149 PMCID: PMC9724288 DOI: 10.1186/s12868-022-00759-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2021] [Accepted: 09/27/2022] [Indexed: 12/12/2022] Open
Abstract
In the military, constant physiological and psychological stress encountered by Soldiers can lead to development of the combat and operational stress reaction (COSR), which can effect pain management. Similar effects are seen in other populations subjected to high levels of stress. Using a model of COSR, our lab recently showed that four weeks of stress prior to an injury increases pain sensitivity in male rats. With the roles of women in the military expanding and recent studies indicating sex differences in stress and pain processing, this study sought to investigate how different amounts of prior stress exposure affects thermal injury-induced mechanosensitivity in a female rat model of COSR. Adult female Sprague Dawley rats were exposed to the unpredictable combat stress (UPCS) procedure for either 2 or 4 weeks. The UPCS procedure included exposure to one stressor each day for four days. The stressors include: (1) sound stress for 30 min, (2) restraint stress for 4 h, (3) cold stress for 4 h, and (4) forced swim stress for 15 min. The order of stressors was randomized weekly. Mechanical and thermal sensitivity was tested twice weekly. After the UPCS procedure, a sub-set of rats received a thermal injury while under anesthesia. The development of mechanical allodynia and thermal hyperalgesia was examined for 14 days post-burn. UPCS exposure increased mechanosensitivity after two weeks. Interestingly, with more stress exposure, females seemed to habituate to the stress, causing the stress-induced changes in mechanosensitivity to decrease by week three of UPCS. If thermal injury induction occurred during peak stress-induced mechanosensitivity, after two weeks, this resulted in increased mechanical allodynia in the injured hind paw compared to thermal injury alone. This data indicates a susceptibility to increased nociceptive sensitization when injury is sustained at peak stress reactivity. Additionally, this data indicates a sex difference in the timing of peak stress. Post-mortem examination of the prefrontal cortex (PFC) showed altered expression of p-TrkB in 4-week stressed animals given a thermal injury, suggesting a compensatory mechanism. Future work will examine treatment options for preventing stress-induced pain to maintain the effectiveness and readiness of the Warfighter.
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Affiliation(s)
- Misty M. Strain
- grid.420328.f0000 0001 2110 0308Pain and Sensory Trauma Care, Combat Research Team 5 (CRT5), US Army Institute of Surgical Research (USAISR), JBSA Fort Sam Houston, 3698 Chambers Pass, San Antonio, TX 78234-4504 USA
| | - Sirima Tongkhuya
- grid.420328.f0000 0001 2110 0308Pain and Sensory Trauma Care, Combat Research Team 5 (CRT5), US Army Institute of Surgical Research (USAISR), JBSA Fort Sam Houston, 3698 Chambers Pass, San Antonio, TX 78234-4504 USA
| | - Nathan Wienandt
- grid.420328.f0000 0001 2110 0308Pain and Sensory Trauma Care, Combat Research Team 5 (CRT5), US Army Institute of Surgical Research (USAISR), JBSA Fort Sam Houston, 3698 Chambers Pass, San Antonio, TX 78234-4504 USA
| | - Farah Alsadoon
- grid.420328.f0000 0001 2110 0308Pain and Sensory Trauma Care, Combat Research Team 5 (CRT5), US Army Institute of Surgical Research (USAISR), JBSA Fort Sam Houston, 3698 Chambers Pass, San Antonio, TX 78234-4504 USA
| | - Roger Chavez
- grid.420328.f0000 0001 2110 0308Pain and Sensory Trauma Care, Combat Research Team 5 (CRT5), US Army Institute of Surgical Research (USAISR), JBSA Fort Sam Houston, 3698 Chambers Pass, San Antonio, TX 78234-4504 USA
| | - Jamar Daniels
- grid.420328.f0000 0001 2110 0308Pain and Sensory Trauma Care, Combat Research Team 5 (CRT5), US Army Institute of Surgical Research (USAISR), JBSA Fort Sam Houston, 3698 Chambers Pass, San Antonio, TX 78234-4504 USA
| | - Thomas Garza
- grid.420328.f0000 0001 2110 0308Pain and Sensory Trauma Care, Combat Research Team 5 (CRT5), US Army Institute of Surgical Research (USAISR), JBSA Fort Sam Houston, 3698 Chambers Pass, San Antonio, TX 78234-4504 USA
| | - Alex V. Trevino
- grid.420328.f0000 0001 2110 0308Pain and Sensory Trauma Care, Combat Research Team 5 (CRT5), US Army Institute of Surgical Research (USAISR), JBSA Fort Sam Houston, 3698 Chambers Pass, San Antonio, TX 78234-4504 USA
| | - Kenney Wells
- grid.420328.f0000 0001 2110 0308Pain and Sensory Trauma Care, Combat Research Team 5 (CRT5), US Army Institute of Surgical Research (USAISR), JBSA Fort Sam Houston, 3698 Chambers Pass, San Antonio, TX 78234-4504 USA
| | - Thomas Stark
- grid.420328.f0000 0001 2110 0308Pain and Sensory Trauma Care, Combat Research Team 5 (CRT5), US Army Institute of Surgical Research (USAISR), JBSA Fort Sam Houston, 3698 Chambers Pass, San Antonio, TX 78234-4504 USA
| | - John Clifford
- grid.420328.f0000 0001 2110 0308Pain and Sensory Trauma Care, Combat Research Team 5 (CRT5), US Army Institute of Surgical Research (USAISR), JBSA Fort Sam Houston, 3698 Chambers Pass, San Antonio, TX 78234-4504 USA
| | - Natasha M. Sosanya
- grid.420328.f0000 0001 2110 0308Pain and Sensory Trauma Care, Combat Research Team 5 (CRT5), US Army Institute of Surgical Research (USAISR), JBSA Fort Sam Houston, 3698 Chambers Pass, San Antonio, TX 78234-4504 USA
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Application of Magnetic Resonance DTI Technique in Evaluating the Effect of Postoperative Exercise Rehabilitation. JOURNAL OF HEALTHCARE ENGINEERING 2022; 2022:2385699. [PMID: 35356626 PMCID: PMC8960000 DOI: 10.1155/2022/2385699] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/20/2021] [Accepted: 06/24/2021] [Indexed: 12/02/2022]
Abstract
Magnetic resonance diffusion tensor imaging (DTI) is a new kind of magnetic resonance imaging technology. Its imaging principle is to distinguish different pathological tissues according to the movement of water molecules, which is higher than regular magnetic resonance diffusion-weighted imaging. Magnetic resonance diffusion tensor imaging has exact utility price in medical analysis and sickness evaluation. However, there are few researches on the utility of diffusion tensor imaging in the rehabilitation comparison of patients. This paper explores the utility of magnetic resonance DTI science in evaluating the impact of postoperative patients' exercising rehabilitation. Taking stroke patients as an example, through giving patients rehabilitation training method, using magnetic resonance DTI technology, the motor function rehabilitation of patients was evaluated, and FA changes of the affected side and healthy side and Fugl–Meyer score of two groups of patients before and after rehabilitation were observed. The software outcomes exhibit that, in the contrast of rehabilitation therapy impact of motor feature in sufferers with cerebral infarction, the use of magnetic resonance DTI technological know-how gives a foundation for clinicians to deeply apprehend the CST involvement of patients, which helps to scientifically evaluate the effect and quality of limb motor rehabilitation training of patients and provides a basis for disease treatment.
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Yang Y, Zhang Q, Ren J, Zhu Q, Wang L, Geng Z. In vivo symmetric multi-contrast MRI brain templates and atlas for spontaneously hypertensive rats. Brain Struct Funct 2022; 227:1789-1801. [PMID: 35318503 DOI: 10.1007/s00429-022-02472-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2021] [Accepted: 02/07/2022] [Indexed: 12/22/2022]
Abstract
Spontaneously hypertensive rats (SHRs) are a valuable animal model of essential hypertension. The increasing use of SHRs in neuroimaging has generated an urgent demand for a template set that provides a reference for advanced data analysis. Structural T2-weighted magnetic resonance imaging (MRI), diffusion tensor imaging (DTI) and functional MRI scans that were used to build the template set were obtained from 8 SHRs longitudinally scanned in vivo at 10, 24 and 52 weeks of age. These symmetric multi-contrast templates were constructed by iterative registration and averaging. The cortical atlas was derived from the Tohoku atlas, and the subcortical regions were manually delineated based on the templates. A set of SHR brain images named the Hebei Medical University rat brain template set (HRT) comprised 3D symmetric T2WI, raw T2-weighted signal with no added diffusion weighting (B0), fractional anisotropy (FA), mean diffusivity (MD) and blood oxygen level-dependent (BOLD) templates; tissue probability maps (TPMs) of gray matter (GM), white matter (WM) and cerebrospinal fluid (CSF); and a whole-brain atlas with 163 labels. We quantitatively validated the template and characterized the longitudinal changes in brain morphology in different brain tissues as SHRs aged. To our knowledge, the HRT is the first MRI template set for SHRs. We believe that the HRT can serve as a beneficial tool for precise analysis of the SHR brain using structural and functional MRI, which can promote neuroimaging studies on essential hypertension.
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Affiliation(s)
- Yingying Yang
- Graduate School, Hebei Medical University, Hebei, 050000, China.,Department of Imaging, The First Hospital of Qinhuangdao, Hebei, 066000, China
| | - Quan Zhang
- Department of Radiology and Tianjin Key Laboratory of Functional Imaging, Tianjin Medical University General Hospital, Tianjin, 300052, China
| | | | - Qingfeng Zhu
- Department of Medical Imaging, The Second Hospital of Hebei Medical University, No. 215 Heping West Road, Xinhua District, Shijiazhuang City, 050000, Hebei Province, China
| | - Lixin Wang
- Department of Medical Imaging, The Second Hospital of Hebei Medical University, No. 215 Heping West Road, Xinhua District, Shijiazhuang City, 050000, Hebei Province, China
| | - Zuojun Geng
- Department of Medical Imaging, The Second Hospital of Hebei Medical University, No. 215 Heping West Road, Xinhua District, Shijiazhuang City, 050000, Hebei Province, China.
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9
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Glioma invasion along white matter tracts: A dilemma for neurosurgeons. Cancer Lett 2022; 526:103-111. [PMID: 34808285 DOI: 10.1016/j.canlet.2021.11.020] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2021] [Revised: 11/15/2021] [Accepted: 11/16/2021] [Indexed: 12/15/2022]
Abstract
Invasive growth along white matter (WM) tracts is one of the most prominent clinicopathological features of glioma and is also an important reason for surgical treatment failure in glioma patients. A full understanding of relevant clinical features and mechanisms is of great significance for finding new therapeutic targets and developing new treatment regimens and strategies. Herein, we review the imaging and histological characteristics of glioma patients with WM tracts invasion and summarize the possible molecular mechanism. On this basis, we further discuss the correlation between glioma molecular typing, radiotherapy and tumor treating fields (TTFields) and the invasion of glioma along WM tracts.
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10
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Johnson GA, Laoprasert R, Anderson RJ, Cofer G, Cook J, Pratson F, White LE. A multicontrast MR atlas of the Wistar rat brain. Neuroimage 2021; 242:118470. [PMID: 34391877 PMCID: PMC8754086 DOI: 10.1016/j.neuroimage.2021.118470] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2020] [Revised: 07/01/2021] [Accepted: 08/11/2021] [Indexed: 11/23/2022] Open
Abstract
We describe a multi-contrast, multi-dimensional atlas of the Wistar rat acquired at microscopic spatial resolution using magnetic resonance histology (MRH). Diffusion weighted images, and associated scalar images were acquired of a single specimen with a fully sampled Fourier reconstruction, 61 angles and b=3000 s/mm2 yielding 50 um isotropic spatial resolution. The higher angular sampling allows use of the GQI algorithm improving the angular invariance of the scalar images and yielding an orientation distribution function to assist in delineating subtle boundaries where there are crossing fibers and track density images providing insight into local fiber architecture. A multigradient echo image of the same specimen was acquired at 25 um isotropic spatial resolution. A quantitative susceptibility map enhances fiber architecture relative to the magnitude images. An accompanying multi-specimen atlas (n=6) was acquired with compressed sensing with the same diffusion protocol as used for the single specimen atlas. An average was created using diffeomorphic mapping. Scalar volumes from the diffusion data, a T2* weighted volume, a quantitative susceptibility map, and a track density volume, all registered to the same space provide multiple contrasts to assist in anatomic delineation. The new template provides significantly increased contrast in the scalar DTI images when compared to previous atlases. A compact interactive viewer based on 3D Slicer is provided to facilitate comparison among the contrasts in the multiple volumes. The single volume and average atlas with multiple 3D volumes provide an improved template for anatomic interrogation of the Wistar rat brain. The improved contrast to noise in the scalar DTI images and the addition of other volumes (eg. QA,QSM,TDI ) will facilitate automated label registration for MR histology and preclinical imaging.
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Affiliation(s)
- G Allan Johnson
- Center for In Vivo Microscopy, Department of Radiology, Duke University Medical Center, Durham, NC 27710, USA; Department of Biomedical Engineering, Duke University, Durham, NC 27710, USA.
| | - Rick Laoprasert
- Center for In Vivo Microscopy, Department of Radiology, Duke University Medical Center, Durham, NC 27710, USA
| | - Robert J Anderson
- Center for In Vivo Microscopy, Department of Radiology, Duke University Medical Center, Durham, NC 27710, USA
| | - Gary Cofer
- Center for In Vivo Microscopy, Department of Radiology, Duke University Medical Center, Durham, NC 27710, USA
| | - James Cook
- Center for In Vivo Microscopy, Department of Radiology, Duke University Medical Center, Durham, NC 27710, USA
| | - Forrest Pratson
- Center for In Vivo Microscopy, Department of Radiology, Duke University Medical Center, Durham, NC 27710, USA
| | - Leonard E White
- Department of Neurology, Duke University Medical Center, Durham, NC 27710, USA
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11
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Sinke MRT, van Tilborg GAF, Meerwaldt AE, van Heijningen CL, van der Toorn A, Straathof M, Rakib F, Ali MHM, Al-Saad K, Otte WM, Dijkhuizen RM. Remote Corticospinal Tract Degeneration After Cortical Stroke in Rats May Not Preclude Spontaneous Sensorimotor Recovery. Neurorehabil Neural Repair 2021; 35:1010-1019. [PMID: 34546138 PMCID: PMC8593321 DOI: 10.1177/15459683211041318] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Background. Recovery of motor function after stroke appears to be related to the integrity of axonal connections in the corticospinal tract (CST) and corpus callosum, which may both be affected after cortical stroke. Objective. In the present study, we aimed to elucidate the relationship of changes in measures of the CST and transcallosal tract integrity, with the interhemispheric functional connectivity and sensorimotor performance after experimental cortical stroke. Methods. We conducted in vivo diffusion magnetic resonance imaging (MRI), resting-state functional MRI, and behavior testing in twenty-five male Sprague Dawley rats recovering from unilateral photothrombotic stroke in the sensorimotor cortex. Twenty-three healthy rats served as controls. Results. A reduction in the number of reconstructed fibers, a lower fractional anisotropy, and higher radial diffusivity in the ipsilesional but intact CST, reflected remote white matter degeneration. In contrast, transcallosal tract integrity remained preserved. Functional connectivity between the ipsi- and contralesional forelimb regions of the primary somatosensory cortex significantly reduced at week 8 post-stroke. Comparably, usage of the stroke-affected forelimb was normal at week 28, following significant initial impairment between day 1 and week 8 post-stroke. Conclusions. Our study shows that post-stroke motor recovery is possible despite degeneration in the CST and may be supported by intact neuronal communication between hemispheres.
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Affiliation(s)
- Michel R T Sinke
- Biomedical MR Imaging and Spectroscopy Group, Center for Image Sciences, University Medical Center Utrecht and Utrecht University, Utrecht, The Netherlands
| | - Geralda A F van Tilborg
- Biomedical MR Imaging and Spectroscopy Group, Center for Image Sciences, University Medical Center Utrecht and Utrecht University, Utrecht, The Netherlands
| | - Anu E Meerwaldt
- Biomedical MR Imaging and Spectroscopy Group, Center for Image Sciences, University Medical Center Utrecht and Utrecht University, Utrecht, The Netherlands
| | - Caroline L van Heijningen
- Biomedical MR Imaging and Spectroscopy Group, Center for Image Sciences, University Medical Center Utrecht and Utrecht University, Utrecht, The Netherlands
| | - Annette van der Toorn
- Biomedical MR Imaging and Spectroscopy Group, Center for Image Sciences, University Medical Center Utrecht and Utrecht University, Utrecht, The Netherlands
| | - Milou Straathof
- Biomedical MR Imaging and Spectroscopy Group, Center for Image Sciences, University Medical Center Utrecht and Utrecht University, Utrecht, The Netherlands
| | - Fazle Rakib
- Department of Chemistry and Earth Sciences, 108740College of Arts and Sciences, Qatar University, Doha, Qatar
| | - Mohamed H M Ali
- Neurological Disorders Research Center, Qatar Biomedical Research Institute (QBRI), 370593Hamad Bin Khalifa University (HBKU), Doha, Qatar
| | - Khalid Al-Saad
- Department of Chemistry and Earth Sciences, 108740College of Arts and Sciences, Qatar University, Doha, Qatar
| | - Willem M Otte
- Biomedical MR Imaging and Spectroscopy Group, Center for Image Sciences, University Medical Center Utrecht and Utrecht University, Utrecht, The Netherlands.,Department of Child Neurology, University Medical Center Utrecht and Utrecht University, 526115UMC Utrecht Brain Center, Utrecht, The Netherlands
| | - Rick M Dijkhuizen
- Biomedical MR Imaging and Spectroscopy Group, Center for Image Sciences, University Medical Center Utrecht and Utrecht University, Utrecht, The Netherlands
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12
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Bubb EJ, Nelson AJD, Cozens TC, Aggleton JP. Organisation of cingulum bundle fibres connecting the anterior thalamic nuclei with the rodent anterior cingulate and retrosplenial cortices. Brain Neurosci Adv 2020. [PMID: 32964131 PMCID: PMC7488606 DOI: 10.1177/2398212820957160] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022] Open
Abstract
Despite considerable interest in the properties of the cingulum bundle, descriptions of the composition of this major pathway in the rodent brain have not kept pace with advances in tract tracing. Using complementary approaches in rats and mice, this study examined the dense, reciprocal connections the anterior thalamic nuclei have with the cingulate and retrosplenial cortices, connections thought to be major contributors to the rodent cingulum bundle. The rat data came from a mixture of fluorescent and viral tracers, some injected directly into the bundle. The mouse data were collated from the Allen Mouse Brain Atlas. The projections from the three major anterior thalamic nuclei occupied much of the external medullary stratum of the cingulum bundle, where they were concentrated in its more medial portions. These anterior thalamic projections formed a rostral-reaching basket of efferents prior to joining the cingulum bundle, with anteromedial efferents taking the most rostral routes, often reaching the genu of the corpus callosum, while anterodorsal efferents took the least rostral route. In contrast, the return cortico-anterior thalamic projections frequently crossed directly through the bundle or briefly joined the internal stratum of the cingulum bundle, often entering the internal capsule before reaching the anterior thalamus. These analyses confirm that anterior thalamic connections comprise an important component of the rodent cingulum bundle, while also demonstrating the very different routes used by thalamo-cortical and cortico-thalamic projections. This information reveals how the composition of the cingulum bundle alters along its length.
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Affiliation(s)
- Emma J. Bubb
- School of Psychology, Cardiff University, Cardiff, Wales, UK
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13
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Müller HP, Roselli F, Rasche V, Kassubek J. Diffusion Tensor Imaging-Based Studies at the Group-Level Applied to Animal Models of Neurodegenerative Diseases. Front Neurosci 2020; 14:734. [PMID: 32982659 PMCID: PMC7487414 DOI: 10.3389/fnins.2020.00734] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2020] [Accepted: 06/22/2020] [Indexed: 12/11/2022] Open
Abstract
The understanding of human and non-human microstructural brain alterations in the course of neurodegenerative diseases has substantially improved by the non-invasive magnetic resonance imaging (MRI) technique of diffusion tensor imaging (DTI). Animal models (including disease or knockout models) allow for a variety of experimental manipulations, which are not applicable to humans. Thus, the DTI approach provides a promising tool for cross-species cross-sectional and longitudinal investigations of the neurobiological targets and mechanisms of neurodegeneration. This overview with a systematic review focuses on the principles of DTI analysis as used in studies at the group level in living preclinical models of neurodegeneration. The translational aspect from in-vivo animal models toward (clinical) applications in humans is covered as well as the DTI-based research of the non-human brains' microstructure, the methodological aspects in data processing and analysis, and data interpretation at different abstraction levels. The aim of integrating DTI in multiparametric or multimodal imaging protocols will allow the interrogation of DTI data in terms of directional flow of information and may identify the microstructural underpinnings of neurodegeneration-related patterns.
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Affiliation(s)
| | - Francesco Roselli
- Department of Neurology, University of Ulm, Ulm, Germany.,German Center for Neurodegenerative Diseases (DZNE), Ulm, Germany
| | - Volker Rasche
- Core Facility Small Animal MRI, University of Ulm, Ulm, Germany
| | - Jan Kassubek
- Department of Neurology, University of Ulm, Ulm, Germany
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14
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Marinković I, Tatlisumak T, Abo-Ramadan U, Brkić BG, Aksić M, Marinković S. A basic MRI anatomy of the rat brain in coronal sections for practical guidance to neuroscientists. Brain Res 2020; 1747:147021. [PMID: 32755602 DOI: 10.1016/j.brainres.2020.147021] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2019] [Revised: 07/08/2020] [Accepted: 07/16/2020] [Indexed: 11/16/2022]
Abstract
Identification of the brain structures in the magnetic resonance imaging (MRI) of the rat is very important for the experimental work of many neuroscientists. Our intention was to recognize most of the structures without overlapping the MRI sections with the histological templates. Three live rats were used for this study who were examined in a micro-MRI apparatus by performing T2-weighted sequences in serial brain sections. Most of the white matter structures were easily identified, e.g. the anterior commissure, corpus callosum with forceps minor and major, cingulum, external and internal capsules, fornix, stria medullaris and terminalis, cranial nerves, mammillothalamic tract, fasciculus retroflexus, medial and lateral lemniscus, posterior commissure, commissures of the superior and inferior colliculi, medial longitudinal fasciculus, and the cerebral peduncle. Large and small gray matter structures were recognized as well, for example, the anterior olfactory structures, nucleus accumbens, caudate putamen, claustrum, bed nucleus of the stria terminalis, pituitary gland, globus pallidus, amygdala, some midline and intralaminar thalamic nuclei, certain hypothalamic nuclei, hippocampal formation, pineal body, periaqueductal gray matter, lateral and medial geniculate bodies, superior and inferior colliculi, and cranial nerves nuclei. All in all, of the total 160 recognized brain structures, 77 were identified without using the corresponding histological atlases. We believe that our labeled MRI pictures could be an important way for quick orientation for evaluating the effects of the experimental work regarding the rat brain.
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Affiliation(s)
- Ivan Marinković
- Clinical Neuroscience, Neurology, Helsinki University Hospital, Haartmaninkatu 4, 00290 Helsinki, Finland.
| | - Turgut Tatlisumak
- Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Blå Stråket 7, Plan 3, Sahlgrenska 41345, Gothenburg, Sweden; Department of Neurology, Sahlgrenska University Hospital, Blå Stråket 7, Plan 3, Sahlgrenska 41345, Gothenburg, Sweden.
| | - Usama Abo-Ramadan
- VTT Technical Research Centre of Finland Ltd, University of Helsinki, Tietotie 4E, 02150 Espoo, Finland
| | | | - Milan Aksić
- Department of Neuroanatomy, Institute of Anatomy, Faculty of Medicine, University of Belgrade, Belgrade, Serbia
| | - Slobodan Marinković
- Department of Neuroanatomy, Institute of Anatomy, Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
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15
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Lee TH, Yang JT, Lin JR, Hu CJ, Chou WH, Lin CP, Chi NF. Protective effects of ischemic preconditioning against neuronal apoptosis and dendritic injury in the hippocampus are age-dependent. J Neurochem 2020; 155:430-447. [PMID: 32314365 DOI: 10.1111/jnc.15029] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2020] [Revised: 04/02/2020] [Accepted: 04/03/2020] [Indexed: 12/13/2022]
Abstract
Ischemic preconditioning with non-lethal ischemia can be protective against lethal forebrain ischemia. We hypothesized that aging may aggravate ischemic susceptibility and reduce brain plasticity against preconditioning. Magnetic resonance diffusion tensor imaging (DTI) is a sensitive tool to detect brain integrity and white matter architecture. This study used DTI and histopathology to investigate the effect of aging on ischemic preconditioning. In this study, adult and middle-aged male Mongolian gerbils were subjected to non-lethal 5-min forebrain ischemia (ischemic preconditioning) or sham-operation, followed by 3 days of reperfusion, and then lethal 15-min forebrain ischemia. A 9.4-Tesla MR imaging system was used to study DTI indices, namely fractional anisotropy (FA), mean diffusivity (MD), and intervoxel coherence (IC) in the hippocampal CA1 and dentate gyrus (DG) areas. In situ expressions of microtubule-associated protein 2 (MAP2, dendritic marker protein) and apoptosis were also examined. The 5-min ischemia did not cause dendritic and neuronal injury and any significant change in DTI indices and MAP2 in adult and middle-aged gerbils. The 15-min ischemia-induced significant delayed neuronal apoptosis and early dendritic injury evidenced by DTI and MAP2 studies in both CA1 and DG areas with more severe injury in middle-aged gerbils than adult gerbils. Ischemic preconditioning could improve neuronal apoptosis in CA1 area and dendritic integrity in both CA1 and DG areas with better improvement in adult gerbils than middle-aged gerbils. This study thus suggests an age-dependent protective effect of ischemic preconditioning against both neuronal apoptosis and dendritic injury in hippocampus after forebrain ischemia.
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Affiliation(s)
- Tsong-Hai Lee
- Stroke Center and Department of Neurology, Chang Gung Memorial Hospital, Linkou Medical Center, and College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Jen-Tsung Yang
- Department of Neurosurgery, Chiayi Chang Gung Memorial Hospital and College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Jr-Rung Lin
- Clinical Informatics and Medical Statistics Research Center, Chang Gung University, Taoyuan, Taiwan
| | - Chaur-Jong Hu
- Department of Neurology, Shuang-Ho Hospital, Taipei Medical University, New Taipei City, Taiwan
| | - Wen-Hai Chou
- Center for Neuropsychiatric Research, National Health Research Institutes, Miaoli, Taiwan
| | - Ching-Po Lin
- Institute of Neuroscience, National Yang-Ming University, Taipei, Taiwan
| | - Nai-Fang Chi
- Department of Neurology, Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan
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16
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Barrière DA, Magalhães R, Novais A, Marques P, Selingue E, Geffroy F, Marques F, Cerqueira J, Sousa JC, Boumezbeur F, Bottlaender M, Jay TM, Cachia A, Sousa N, Mériaux S. The SIGMA rat brain templates and atlases for multimodal MRI data analysis and visualization. Nat Commun 2019; 10:5699. [PMID: 31836716 PMCID: PMC6911097 DOI: 10.1038/s41467-019-13575-7] [Citation(s) in RCA: 75] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2019] [Accepted: 10/23/2019] [Indexed: 11/08/2022] Open
Abstract
Preclinical imaging studies offer a unique access to the rat brain, allowing investigations that go beyond what is possible in human studies. Unfortunately, these techniques still suffer from a lack of dedicated and standardized neuroimaging tools, namely brain templates and descriptive atlases. Here, we present two rat brain MRI templates and their associated gray matter, white matter and cerebrospinal fluid probability maps, generated from ex vivo [Formula: see text]-weighted images (90 µm isotropic resolution) and in vivo T2-weighted images (150 µm isotropic resolution). In association with these templates, we also provide both anatomical and functional 3D brain atlases, respectively derived from the merging of the Waxholm and Tohoku atlases, and analysis of resting-state functional MRI data. Finally, we propose a complete set of preclinical MRI reference resources, compatible with common neuroimaging software, for the investigation of rat brain structures and functions.
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Affiliation(s)
- D A Barrière
- NeuroSpin, Institut des Sciences du Vivant Frédéric Joliot, Commissariat à l'Énergie Atomique et aux Énergies Alternatives, 91191, Gif-Sur-Yvette, France
- Université Paris-Saclay, 91191, Gif-Sur-Yvette, France
- Université de Paris, Institut de Psychiatrie et Neurosciences de Paris, INSERM, 75005, Paris, France
| | - R Magalhães
- NeuroSpin, Institut des Sciences du Vivant Frédéric Joliot, Commissariat à l'Énergie Atomique et aux Énergies Alternatives, 91191, Gif-Sur-Yvette, France
- Université Paris-Saclay, 91191, Gif-Sur-Yvette, France
- Life And Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, 4710-057, Braga, Portugal
- ICVS/3B's, PT Government Associate Laboratory, Braga, Guimarães, Portugal
| | - A Novais
- Life And Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, 4710-057, Braga, Portugal
- ICVS/3B's, PT Government Associate Laboratory, Braga, Guimarães, Portugal
| | - P Marques
- Life And Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, 4710-057, Braga, Portugal
- ICVS/3B's, PT Government Associate Laboratory, Braga, Guimarães, Portugal
| | - E Selingue
- NeuroSpin, Institut des Sciences du Vivant Frédéric Joliot, Commissariat à l'Énergie Atomique et aux Énergies Alternatives, 91191, Gif-Sur-Yvette, France
- Université Paris-Saclay, 91191, Gif-Sur-Yvette, France
| | - F Geffroy
- NeuroSpin, Institut des Sciences du Vivant Frédéric Joliot, Commissariat à l'Énergie Atomique et aux Énergies Alternatives, 91191, Gif-Sur-Yvette, France
- Université Paris-Saclay, 91191, Gif-Sur-Yvette, France
| | - F Marques
- Life And Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, 4710-057, Braga, Portugal
- ICVS/3B's, PT Government Associate Laboratory, Braga, Guimarães, Portugal
| | - J Cerqueira
- Life And Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, 4710-057, Braga, Portugal
- ICVS/3B's, PT Government Associate Laboratory, Braga, Guimarães, Portugal
| | - J C Sousa
- Life And Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, 4710-057, Braga, Portugal
- ICVS/3B's, PT Government Associate Laboratory, Braga, Guimarães, Portugal
| | - F Boumezbeur
- NeuroSpin, Institut des Sciences du Vivant Frédéric Joliot, Commissariat à l'Énergie Atomique et aux Énergies Alternatives, 91191, Gif-Sur-Yvette, France
- Université Paris-Saclay, 91191, Gif-Sur-Yvette, France
| | - M Bottlaender
- NeuroSpin, Institut des Sciences du Vivant Frédéric Joliot, Commissariat à l'Énergie Atomique et aux Énergies Alternatives, 91191, Gif-Sur-Yvette, France
- Université Paris-Saclay, 91191, Gif-Sur-Yvette, France
| | - T M Jay
- Université de Paris, Institut de Psychiatrie et Neurosciences de Paris, INSERM, 75005, Paris, France
| | - A Cachia
- Université de Paris, Institut de Psychiatrie et Neurosciences de Paris, INSERM, 75005, Paris, France
- Université de Paris, Laboratoire de Psychologie du Développement et de l'Éducation de l'Enfant, CNRS, 75005, Paris, France
- Institut Universitaire de France, 75005, Paris, France
| | - N Sousa
- Life And Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, 4710-057, Braga, Portugal.
- ICVS/3B's, PT Government Associate Laboratory, Braga, Guimarães, Portugal.
| | - S Mériaux
- NeuroSpin, Institut des Sciences du Vivant Frédéric Joliot, Commissariat à l'Énergie Atomique et aux Énergies Alternatives, 91191, Gif-Sur-Yvette, France.
- Université Paris-Saclay, 91191, Gif-Sur-Yvette, France.
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17
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Sosanya NM, Garza TH, Stacey W, Crimmins SL, Christy RJ, Cheppudira BP. Involvement of brain-derived neurotrophic factor (BDNF) in chronic intermittent stress-induced enhanced mechanical allodynia in a rat model of burn pain. BMC Neurosci 2019; 20:17. [PMID: 31014242 PMCID: PMC6480655 DOI: 10.1186/s12868-019-0500-1] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2018] [Accepted: 04/10/2019] [Indexed: 12/30/2022] Open
Abstract
BACKGROUND Reports show that stressful events before injury exacerbates post-injury pain. The mechanism underlying stress-induced heightened thermal pain is unclear. Here, we examined the effects of chronic intermittent stress (CIS) on nociceptive behaviors and brain-derived nerve growth factor (BDNF) system in the prefrontal cortex (PFC) and hypothalamus of rats with and without thermal injury. RESULTS Unstressed rats showed transient mechanical allodynia during stress exposure. Stressed rats with thermal injury displayed persistent exacerbated mechanical allodynia (P < 0.001). Increased expression of BDNF mRNA in the PFC (P < 0.05), and elevated TrkB and p-TrkB (P < 0.05) protein levels in the hypothalamus were observed in stressed rats with thermal injury but not in stressed or thermally injured rats alone. Furthermore, administration of CTX-B significantly reduced stress-induced exacerbated mechanical allodynia in thermally injured rats (P < 0.001). CONCLUSION These results indicate that BDNF-TrkB signaling in PFC and hypothalamus contributes to CIS-induced exacerbated mechanical allodynia in thermal injury state.
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Affiliation(s)
- Natasha M Sosanya
- Battlefield Pain Management Research Group, United States Army Institute of Surgical Research, 3698 Chambers Pass, JBSA Fort Sam Houston, San Antonio, TX, 78234-4504, USA
| | - Thomas H Garza
- Battlefield Pain Management Research Group, United States Army Institute of Surgical Research, 3698 Chambers Pass, JBSA Fort Sam Houston, San Antonio, TX, 78234-4504, USA
| | - Winfred Stacey
- Battlefield Pain Management Research Group, United States Army Institute of Surgical Research, 3698 Chambers Pass, JBSA Fort Sam Houston, San Antonio, TX, 78234-4504, USA
| | - Stephen L Crimmins
- Battlefield Pain Management Research Group, United States Army Institute of Surgical Research, 3698 Chambers Pass, JBSA Fort Sam Houston, San Antonio, TX, 78234-4504, USA
| | - Robert J Christy
- Battlefield Pain Management Research Group, United States Army Institute of Surgical Research, 3698 Chambers Pass, JBSA Fort Sam Houston, San Antonio, TX, 78234-4504, USA
| | - Bopaiah P Cheppudira
- Battlefield Pain Management Research Group, United States Army Institute of Surgical Research, 3698 Chambers Pass, JBSA Fort Sam Houston, San Antonio, TX, 78234-4504, USA.
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Rat brain digital stereotaxic white matter atlas with fine tract delineation in Paxinos space and its automated applications in DTI data analysis. Magn Reson Imaging 2017; 43:122-128. [DOI: 10.1016/j.mri.2017.07.011] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2017] [Revised: 07/07/2017] [Accepted: 07/13/2017] [Indexed: 12/25/2022]
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19
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Song H, Jung W, Lee E, Park JY, Kim MS, Lee MC, Kim HI. Capsular stroke modeling based on somatotopic mapping of motor fibers. J Cereb Blood Flow Metab 2017; 37:2928-2937. [PMID: 27837188 PMCID: PMC5536800 DOI: 10.1177/0271678x16679421] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Recently, several capsular stroke models have been reported with different targets of destruction. This study was performed to establish an accurate internal capsule (IC) target for capsular stroke modeling in rats. We injected adeno-associated virus serotype 5 (AAV)-CaMKII-EYFP into forelimb motor cortex and AAV-CaMKII-mCherry into hindlimb motor cortex (n = 9) to anterogradely trace the pyramidal fibers and map their somatotopic distribution in the IC. On the basis of the neural tracing results, we created photothrombotic infarct lesions in rat forelimb and hindlimb motor fiber (FMF and HMF) areas of the IC (n = 29) and assessed motor behavior using a forelimb-use asymmetry test, a foot-fault test, and a single-pellet reaching test. We found that the FMFs and HMFs were primarily distributed in the inferior portion of the posterior limb of the IC, with the FMFs located largely ventral to the HMFs but with an area of partial overlap. Photothrombotic lesions in the FMF area resulted in persistent motor deficits. In contrast, lesions in the HMF area did not result in persistent motor deficits. These results indicate that identification of the somatotopic distribution of pyramidal fibers is critical for accurate targeting in animal capsular stroke models: only infarcts in the FMF area resulted in long-lasting motor deficits.
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Affiliation(s)
- Hanlim Song
- 1 Department of Biomedical Science and Engineering, Gwangju Institute of Science and Technology, Gwangju, Republic of Korea
| | - Wonbin Jung
- 1 Department of Biomedical Science and Engineering, Gwangju Institute of Science and Technology, Gwangju, Republic of Korea
| | - Eulgi Lee
- 1 Department of Biomedical Science and Engineering, Gwangju Institute of Science and Technology, Gwangju, Republic of Korea
| | - Ji-Young Park
- 1 Department of Biomedical Science and Engineering, Gwangju Institute of Science and Technology, Gwangju, Republic of Korea
| | - Min Sun Kim
- 2 Department of Physiology, Wonkwang University School of Medicine, Iksan, Republic of Korea
| | - Min-Cheol Lee
- 3 Department of Pathology, Chonnam National University Medical School, Gwangju, Republic of Korea
| | - Hyoung-Ihl Kim
- 1 Department of Biomedical Science and Engineering, Gwangju Institute of Science and Technology, Gwangju, Republic of Korea.,4 Department of Neurosurgery, Presbyterian Medical Center, Jeonju, Republic of Korea
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20
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Yang GT, Zhao HY, Kong Y, Sun NN, Dong AQ. Study of the effects of nesfatin-1 on gastric function in obese rats. World J Gastroenterol 2017; 23:2940-2947. [PMID: 28522911 PMCID: PMC5413788 DOI: 10.3748/wjg.v23.i16.2940] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/01/2016] [Revised: 02/15/2017] [Accepted: 03/02/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate the effects of nesfatin-1 on gastric function in obese rats.
METHODS The obese rat model was induced by a high-fat diet. The gastric emptying rate and gastric acid secretory capacity of the rats were determined after treatment with different drug concentrations of nesfatin-1 and administration routes. Based on this, the expression of H+/K+-ATPase was measured using RT-PCR and western blot to preliminarily explore the mechanism of gastric acid secretion changes.
RESULTS Body weight, body length, and Lee’s index of the rats significantly increased in the high-fat diet-induced obese rat model. Two hours after lateral intracerebroventricular injection of nesfatin-1, the gastric emptying rate and gastric acid secretory capacity of rats decreased. Four hours after injection, both were restored to normal levels. In addition, the expression of H+/K+-ATPase decreased and moved in line with changes in gastric acid secretory capacity. This in vivo experiment revealed that intracerebroventricular injection of nesfatin-1, rather than intravenous injection, could suppress gastric function in obese rats. Moreover, its effect on the gastric emptying and gastric acid secretory capacity of rats is dose-dependent within a certain period of time.
CONCLUSION Through this research, we provide a theoretical basis for further studies on nesfatin-1, a potential anti-obesity drug.
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21
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Azimi N, Yadollahikhales G, Argenti JP, Cunningham MG. Discrepancies in stereotaxic coordinate publications and improving precision using an animal-specific atlas. J Neurosci Methods 2017; 284:15-20. [PMID: 28392415 DOI: 10.1016/j.jneumeth.2017.03.019] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2017] [Revised: 03/24/2017] [Accepted: 03/27/2017] [Indexed: 10/19/2022]
Abstract
Rodent brain atlases have traditionally been used to identify brain structures in three-dimensional space for a variety of stereotaxic procedures. As neuroscience becomes increasingly sophisticated, higher levels of precision and consistency are needed. Observations of various atlases currently in use across labs reveal numerous coordinate discrepancies. Here we provide examples of inconsistencies by comparing the coordinates of the boundaries of various brain structures across six atlas publications. We conclude that the coordinates determined by any particular atlas should be considered as only a first approximation of the actual target coordinates for the experimental animal for a particular study. Furthermore, the coordinates determined by one research team cannot be assumed to be universally applicable and accurate in other experimental settings. To optimize precision, we describe a simple protocol for the construction of a customized atlas that is specific to the surgical approach and to the species, gender, and age of the animal used in any given study.
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Affiliation(s)
- Nima Azimi
- Laboratory for Neural Reconstruction, McLean Hospital Department of Psychiatry, 115 Mill Street Belmont, MA 02478, United States
| | - Golnaz Yadollahikhales
- Laboratory for Neural Reconstruction, McLean Hospital Department of Psychiatry, 115 Mill Street Belmont, MA 02478, United States
| | - John Paul Argenti
- Laboratory for Neural Reconstruction, McLean Hospital Department of Psychiatry, 115 Mill Street Belmont, MA 02478, United States
| | - Miles G Cunningham
- Laboratory for Neural Reconstruction, McLean Hospital Department of Psychiatry, 115 Mill Street Belmont, MA 02478, United States.
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22
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Tudela R, Muñoz-Moreno E, López-Gil X, Soria G. Effects of Orientation and Anisometry of Magnetic Resonance Imaging Acquisitions on Diffusion Tensor Imaging and Structural Connectomes. PLoS One 2017; 12:e0170703. [PMID: 28118397 PMCID: PMC5261617 DOI: 10.1371/journal.pone.0170703] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2016] [Accepted: 01/09/2017] [Indexed: 11/19/2022] Open
Abstract
Diffusion-weighted imaging (DWI) quantifies water molecule diffusion within tissues and is becoming an increasingly used technique. However, it is very challenging as correct quantification depends on many different factors, ranging from acquisition parameters to a long pipeline of image processing. In this work, we investigated the influence of voxel geometry on diffusion analysis, comparing different acquisition orientations as well as isometric and anisometric voxels. Diffusion-weighted images of one rat brain were acquired with four different voxel geometries (one isometric and three anisometric in different directions) and three different encoding orientations (coronal, axial and sagittal). Diffusion tensor scalar measurements, tractography and the brain structural connectome were analyzed for each of the 12 acquisitions. The acquisition direction with respect to the main magnetic field orientation affected the diffusion results. When the acquisition slice-encoding direction was not aligned with the main magnetic field, there were more artifacts and a lower signal-to-noise ratio that led to less anisotropic tensors (lower fractional anisotropic values), producing poorer quality results. The use of anisometric voxels generated statistically significant differences in the values of diffusion metrics in specific regions. It also elicited differences in tract reconstruction and in different graph metric values describing the brain networks. Our results highlight the importance of taking into account the geometric aspects of acquisitions, especially when comparing diffusion data acquired using different geometries.
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Affiliation(s)
- Raúl Tudela
- CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Barcelona, Spain
| | | | | | - Guadalupe Soria
- CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Barcelona, Spain
- Experimental MRI 7T Unit, IDIBAPS, Barcelona, Spain
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23
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Naumova AV, Akulov AE, Khodanovich MY, Yarnykh VL. High-resolution three-dimensional macromolecular proton fraction mapping for quantitative neuroanatomical imaging of the rodent brain in ultra-high magnetic fields. Neuroimage 2016; 147:985-993. [PMID: 27646128 DOI: 10.1016/j.neuroimage.2016.09.036] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2016] [Revised: 09/14/2016] [Accepted: 09/16/2016] [Indexed: 11/24/2022] Open
Abstract
A well-known problem in ultra-high-field MRI is generation of high-resolution three-dimensional images for detailed characterization of white and gray matter anatomical structures. T1-weighted imaging traditionally used for this purpose suffers from the loss of contrast between white and gray matter with an increase of magnetic field strength. Macromolecular proton fraction (MPF) mapping is a new method potentially capable to mitigate this problem due to strong myelin-based contrast and independence of this parameter of field strength. MPF is a key parameter determining the magnetization transfer effect in tissues and defined within the two-pool model as a relative amount of macromolecular protons involved into magnetization exchange with water protons. The objectives of this study were to characterize the two-pool model parameters in brain tissues in ultra-high magnetic fields and introduce fast high-field 3D MPF mapping as both anatomical and quantitative neuroimaging modality for small animal applications. In vivo imaging data were obtained from four adult male rats using an 11.7T animal MRI scanner. Comprehensive comparison of brain tissue contrast was performed for standard R1 and T2 maps and reconstructed from Z-spectroscopic images two-pool model parameter maps including MPF, cross-relaxation rate constant, and T2 of pools. Additionally, high-resolution whole-brain 3D MPF maps were obtained with isotropic 170µm voxel size using the single-point synthetic-reference method. MPF maps showed 3-6-fold increase in contrast between white and gray matter compared to other parameters. MPF measurements by the single-point synthetic reference method were in excellent agreement with the Z-spectroscopic method. MPF values in rat brain structures at 11.7T were similar to those at lower field strengths, thus confirming field independence of MPF. 3D MPF mapping provides a useful tool for neuroimaging in ultra-high magnetic fields enabling both quantitative tissue characterization based on the myelin content and high-resolution neuroanatomical visualization with high contrast between white and gray matter.
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Affiliation(s)
- Anna V Naumova
- University of Washington, Department of Radiology, 850 Republican Street, Seattle, WA, USA; National Research Tomsk State University, Research Institute of Biology and Biophysics, 36 Lenina Avenue, Tomsk, Russia
| | - Andrey E Akulov
- Institute of Cytology and Genetics, The Siberian Branch of the Russian Academy of Sciences, 10 Lavrentyeva Avenue, Novosibirsk, Russia
| | - Marina Yu Khodanovich
- National Research Tomsk State University, Research Institute of Biology and Biophysics, 36 Lenina Avenue, Tomsk, Russia
| | - Vasily L Yarnykh
- University of Washington, Department of Radiology, 850 Republican Street, Seattle, WA, USA; National Research Tomsk State University, Research Institute of Biology and Biophysics, 36 Lenina Avenue, Tomsk, Russia.
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24
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A diffusion tensor imaging atlas of white matter in tree shrew. Brain Struct Funct 2016; 222:1733-1751. [PMID: 27624528 DOI: 10.1007/s00429-016-1304-z] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2016] [Accepted: 09/04/2016] [Indexed: 10/21/2022]
Abstract
Tree shrews are small mammals now commonly classified in the order of Scandentia, but have relatively closer affinity to primates than rodents. The species has a high brain-to-body mass ratio and relatively well-differentiated neocortex, and thus has been frequently used in neuroscience research, especially for studies on vision and neurological/psychiatric diseases. The available atlases on tree shrew brain provided only limited information on white matter (WM) anatomy. In this study, diffusion tensor imaging (DTI) was used to study the WM anatomy of tree shrew, with the goal to establish an image-based WM atlas. DTI and T2-weighted anatomical images were acquired in vivo and from fixed brain samples. Deterministic tractography was used for three-dimensional reconstruction and rendering of major WM tracts. Myelin and neurofilaments staining were used to study the microstructural properties of certain WM tracts. Taking into account prior knowledge on tree shrew neuroanatomy, tractography results, and comparisons to the homologous structures in rodents and primates, an image-based WM atlas of tree shrew brain was constructed, which is available to research community upon request.
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25
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Zhuo Y, Guo H, Cheng Y, Wang C, Wang C, Wu J, Zou Z, Gan D, Li Y, Xu J. Inhibition of phosphodiesterase-4 reverses the cognitive dysfunction and oxidative stress induced by Aβ25-35 in rats. Metab Brain Dis 2016; 31:779-91. [PMID: 26920899 DOI: 10.1007/s11011-016-9814-1] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/09/2015] [Accepted: 02/23/2016] [Indexed: 02/05/2023]
Abstract
Phosphodiesterase-4 (PDE4) inhibitors prevent the breakdown of the second messenger cAMP and have been demonstrated to improve learning in several animal models of cognition. In this study, we explored the antioxidative effects of rolipram in Alzheimer's disease (AD) by using bilateral Aβ25-35 injection into the hippocampus of rats, which were used as an AD model. Rats received 3 intraperitoneal (i.p.) doses of rolipram (0.1, 0.5 and 1.25 mg/kg) daily after the injection of Aβ25-35 for 25 days. Chronic administration of rolipram prevented the memory impairments induced by Aβ25-35, as assessed using the passive avoidance test and the Morris water maze test. Furthermore, rolipram significantly reduced the oxidative stress induced by Aβ25-35, as evidenced by the decrease in the levels of reactive oxygen species (ROS) and malondialdehyde (MDA), and restored the reduced GSH levels and superoxide dismutase (SOD) activity. Moreover, western blotting and real-time reverse transcription polymerase chain reaction (RT-PCR) analysis showed that rolipram remarkably upregulated thioredoxin (Trx) and inhibited the inducible nitric oxide synthase/nitric oxide (iNOS/NO) pathway in the hippocampus. These results demonstrated that rolipram improved the learning and memory abilities in an Aβ25-35-induced AD rat model. The mechanism underlying these effects may be due to the noticeable antioxidative effects of rolipram.
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Affiliation(s)
- Yeye Zhuo
- Department of Pharmacology, Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, Guangdong, 510515, China
- The first affiliated hospital of Shantou University Medical College, Shantou, Guangdong, 515041, China
| | - Haibiao Guo
- Department of Pharmacology, Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, Guangdong, 510515, China
| | - Yufang Cheng
- Department of Pharmacology, Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, Guangdong, 510515, China
| | - Chuang Wang
- Ningbo Key Laboratory of Behavioral Neuroscience, 818 Fenghua Road, Ningbo, Zhejiang, 315211, China
| | - Canmao Wang
- Department of Pharmacy, Shenzhen Hospital of Southern Medical University, Shenzhen, Guangdong, 518000, China
| | - Jingang Wu
- Department of Pharmacology, Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, Guangdong, 510515, China
| | - Zhengqiang Zou
- Department of Pharmacology, Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, Guangdong, 510515, China
| | - Danna Gan
- Department of Pharmacy, Shenzhen Hospital of Southern Medical University, Shenzhen, Guangdong, 518000, China
| | - Yiwen Li
- Department of Pharmacology, Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, Guangdong, 510515, China
| | - Jiangping Xu
- Department of Pharmacology, Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, Guangdong, 510515, China.
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26
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Bao L, Si L, Wang Y, Wuyun G, Bo A. Effect of two GABA-ergic drugs on the cognitive functions of rapid eye movement in sleep-deprived and recovered rats. Exp Ther Med 2016; 12:1075-1084. [PMID: 27446323 DOI: 10.3892/etm.2016.3445] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2015] [Accepted: 03/16/2016] [Indexed: 01/05/2023] Open
Abstract
Rapid eye movement (REM) sleep is closely associated with nervous functions. The present study aimed to evaluate the effects of gabazine and tiagabine on the cognitive functions (CF) of REM sleep-deprived and sleep recovered rats. Rats were divided into REM sleep deprivation, blank control (CC) and environmental groups. The REM sleep deprivation group was further divided into non-operation (nonOP), sham-operated (Sham), gabazine (SR) and tiagabine groups. Each group was evaluated over five time points: Sleep deprived for 1 day (SD 1 day), SD 3 day, SD 5 day, sleep recovery 6 h (RS 6 h) and RS 12 h. A rat model of REM sleep deprivation was established by a modified multi-platform water method, with CF assessed by Morris water maze. Hypothalamic γ-aminobutyric acid (GABA) and glutamic acid contents were measured via high performance liquid chromatography. The number and morphology of hypocretin (Hcrt) neurons and Fos in the hypothalamus, and GABAARα1-induced integral optical density were detected by immunofluorescence. Compared to the CC group, the nonOP and Sham group rats CF were significantly diminished, Fos-positive and Fos-Hcrt double positive cells were significantly increased, and GABA content and GABAARα1 expression levels were significantly elevated (P<0.05). The tiagabine and CC groups exhibited similar results at three time points. The CF of rats in the SR group were diminished and the number of Fos-positive and Fos-Hcrt double positive cells were significantly increased (P<0.05) at RS 6 h and RS l2 h. GABA content and GABAARα1 expression levels were significantly increased in the SR group at all time points (P<0.05), whereas only GABAARα1 expression levels were significantly increased in the tiagabine group at SD 5 day (P<0.05). The results of the present study indicated that REM sleep deprivation diminished CF, increased the number of Hcrt neurons, GABA content and GABAARα1 expression. Furthermore, all alterations were positively correlated with deprivation time and corrected by sleep recovery, as demonstrated by single-factor multi-level variance analysis at the various time points in each group. Therefore, the Hcrt nervous system may be an eligible therapeutic target for the treatment of insomnia.
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Affiliation(s)
- Lidao Bao
- College of Traditional Mongolian Medicine, Inner Mongolia Medical University, Hohhot, Inner Mongolia 010110, P.R. China; Department of Pharmacy, Affiliated Hospital of Inner Mongolia Medical University, Hohhot, Inner Mongolia 010059, P.R. China
| | - Lengge Si
- College of Traditional Mongolian Medicine, Inner Mongolia Medical University, Hohhot, Inner Mongolia 010110, P.R. China
| | - Yuehong Wang
- College of Traditional Mongolian Medicine, Inner Mongolia Medical University, Hohhot, Inner Mongolia 010110, P.R. China
| | - Gerile Wuyun
- College of Traditional Mongolian Medicine, Inner Mongolia Medical University, Hohhot, Inner Mongolia 010110, P.R. China
| | - Agula Bo
- College of Traditional Mongolian Medicine, Inner Mongolia Medical University, Hohhot, Inner Mongolia 010110, P.R. China
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27
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Schier LA, Blonde GD, Spector AC. Bilateral lesions in a specific subregion of posterior insular cortex impair conditioned taste aversion expression in rats. J Comp Neurol 2015; 524:54-73. [PMID: 26053891 DOI: 10.1002/cne.23822] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2015] [Revised: 05/27/2015] [Accepted: 05/27/2015] [Indexed: 11/09/2022]
Abstract
The gustatory cortex (GC) is widely regarded for its integral role in the acquisition and retention of conditioned taste aversions (CTAs) in rodents, but large lesions in this area do not always result in CTA impairment. Recently, using a new lesion mapping system, we found that severe CTA expression deficits were associated with damage to a critical zone that included the posterior half of GC in addition to the insular cortex (IC) that is just dorsal and caudal to this region (visceral cortex). Lesions in anterior GC were without effect. Here, neurotoxic bilateral lesions were placed in the anterior half of this critical damage zone, at the confluence of the posterior GC and the anterior visceral cortex (termed IC2 ), the posterior half of this critical damage zone that contains just VC (termed IC3), or both of these subregions (IC2 + IC3). Then, pre- and postsurgically acquired CTAs (to 0.1 M NaCl and 0.1 M sucrose, respectively) were assessed postsurgically in 15-minute one-bottle and 96-hour two-bottle tests. Li-injected rats with histologically confirmed bilateral lesions in IC2 exhibited the most severe CTA deficits, whereas those with bilateral lesions in IC3 were relatively normal, exhibiting transient disruptions in the one-bottle sessions. Groupwise lesion maps showed that CTA-impaired rats had more extensive damage to IC2 than did unimpaired rats. Some individual differences in CTA expression among rats with similar lesion profiles were observed, suggesting idiosyncrasies in the topographic representation of information in the IC. Nevertheless, this study implicates IC2 as the critical zone of the IC for normal CTA expression.
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Affiliation(s)
- Lindsey A Schier
- Department of Psychology and Program in Neuroscience, Florida State University, Tallahassee, Florida, 32306
| | - Ginger D Blonde
- Department of Psychology and Program in Neuroscience, Florida State University, Tallahassee, Florida, 32306
| | - Alan C Spector
- Department of Psychology and Program in Neuroscience, Florida State University, Tallahassee, Florida, 32306
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