Magnetic resonance histology for morphologic phenotyping

Johnson, G. Allan; Cofer, Gary P.; Fubara, Boma; Gewalt, Sally L.; Hedlund, Laurence W.; Maronpot, Robert R.

doi:10.1002/jmri.10175

Cited by 112 publications

(93 citation statements)

References 14 publications

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“…Imaging in the mouse requires significant hardware and sequence upgrades compared with standard human clinical scanners. However, despite the technical hurdles involved in mouse imaging, several mouse imaging centers have had success in imaging mouse brains with high neuroanatomical resolution [108][109][110][111][112][113], including ours at the Mouse Imaging Centre at the Hospital for Sick Children in Toronto [93,94,114].…”

Section: Discoveries Of Neuroanatomical Abnormalities In Mouse Modelsmentioning

confidence: 99%

Behavioral and Neuroanatomical Phenotypes in Mouse Models of Autism

2015

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In order to understand the consequences of the mutation on behavioral and biological phenotypes relevant to autism, mutations in many of the risk genes for autism spectrum disorder have been experimentally generated in mice. Here, we summarize behavioral outcomes and neuroanatomical abnormalities, with a focus on highresolution magnetic resonance imaging of postmortem mouse brains. Results are described from multiple mouse models of autism spectrum disorder and comorbid syndromes, including the 15q11-13, 16p11.2, 22q11.2, Cntnap2, Engrailed2, Fragile X, Integrinβ3, MET, Neurexin1a, Neuroligin3, Reelin, Rett, Shank3, Slc6a4, tuberous sclerosis, and Williams syndrome models, and inbred strains with strong autism-relevant behavioral phenotypes, including BTBR and BALB. Concomitant behavioral and neuroanatomical abnormalities can strengthen the interpretation of results from a mouse model, and may elevate the usefulness of the model system for therapeutic discovery.

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Section: Discoveries Of Neuroanatomical Abnormalities In Mouse Modelsmentioning

confidence: 99%

Behavioral and Neuroanatomical Phenotypes in Mouse Models of Autism

2015

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“…The COS study extends the use of MRM beyond that of previous studies (Delnomdedieu et al, 1996;Lester et al, 2000;Johnson et al, 2002), because MRM was used to identify major sites of COS neurotoxicity, and the information gained from MRM positively influenced the outcome of our functional and mechanistic studies.…”

Section: Introductionmentioning

confidence: 92%

“…Magnetic resonance microscopy is based on the same principles of MRI (Wheeler and Withers, 1996), but allows for higher resolution and sensitivity (Johnson et al, 2002). Higher resolution is achieved by the use of encoding gradients that are at least 5X-100X higher than those of clinical human MRI systems (Johnson et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

“…Higher resolution is achieved by the use of encoding gradients that are at least 5X-100X higher than those of clinical human MRI systems (Johnson et al, 2002). Greater sensitivity is enhanced by working at higher magnetic fields through the use of specially constructed probes and specialized pulse sequences (Johnson et al, 2002). In this study, MRM (voxels of .07 × .07 × .140 mm) provided ∼5,000 times greater resolution in the rodent brain than in current clinical human brain MRI (voxel of 1 × 1 × 5 mm).…”

Section: Introductionmentioning

confidence: 99%

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Contribution of Magnetic Resonance Microscopy in the 12-Week Neurotoxicity Evaluation of Carbonyl Sulfide in Fischer 344 Rats

et al. 2004

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In this carbonyl sulfide (COS) study, magnetic resonance microscopy (MRM) and detailed light microscopic evaluation effectively functioned in parallel to assure that the distribution and degree of pathology in the brain was accurately represented. MRM is a powerful imaging modality that allows for excellent identification of neuroanatomical structures coupled with the ability to acquire 200 or more cross-sectional images of the brain, and the ability to display them in multiple planes. F344 rats were exposed to 200-600 ppm COS for up to 12 weeks. Prior to MRM, rats were anesthetized and cardiac perfused with McDowell Trump's fixative containing a gadolinium MR contrast medium. Fixed specimens were scanned at the Duke Center for In Vivo Microscopy on a 9.4 Tesla magnetic resonance system adapted explicitly for microscopic imaging. An advantage of MRM in this study was the ability to identify lesions in rats that appeared clinically normal prior to sacrifice and the opportunity to identify lesions in areas of the brain which would not be included in conventional studies. Other advantages include the ability to examine the brain in multiple planes (transverse, dorsal, sagittal) and obtain and save the MRM images in a digital format that allows for postexperimental data processing and manipulation. MRM images were correlated with neuroanatomical and neuropathological findings. All suspected MRM images were compared to corresponding H&E slides. An important aspect of this study was that MRM was critical in defining our strategy for sectioning the brain, and for designing mechanistic studies (cytochrome oxidase evaluations) and functional assessments (electrophysiology studies) on specifically targeted anatomical sites following COS exposure.

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“…MRH complements more traditional methods of histology in four unique ways-MRH is non-destructive; MRH exploits unique contrast mechanisms of water in the tissue; MRH is three-dimensional; and MRH is inherently digital, which makes it possible to readily share morphologic data over the Internet. A number of authors have demonstrated the utility of MRH in the mouse brain (Benveniste et al, 2000;Johnson et al, 2002a;Kovacevic et al, 2005;Ma et al, 2005;MacKenzie-Graham et al, 2004). However, comparing results between these studies is difficult because a wide range of acquisition strategies with varied tissue contrast has been employed.…”

Section: Introductionmentioning

confidence: 99%

High-throughput morphologic phenotyping of the mouse brain with magnetic resonance histology

et al. 2007

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The Mouse Bioinformatics Research Network (MBIRN) has been established to integrate imaging studies of the mouse brain ranging from three-dimensional (3D) studies of the whole brain to focused regions at a sub-cellular scale. Magnetic resonance (MR) histology provides the entry point for many morphologic comparisons of the whole brain. We describe a standardized protocol that allows acquisition of 3D MR histology (43-micron resolution) images of the fixed, stained mouse brain with acquisition times < 30 minutes. A higher-resolution protocol with isotropic spatial resolution of 21.5 microns can be executed in 2 hours. A third acquisition protocol provides an alternative image contrast (at 43-micron isotropic resolution), which is exploited in a statistically driven algorithm that segments 33 of the most critical structures in the brain. The entire process, from specimen perfusion, fixation and staining, image acquisition and reconstruction, post-processing, segmentation, archiving, and analysis is integrated through a structured workflow. This yields a searchable database for archive and query of the very large (1.2 GB) images acquired with this standardized protocol. These methods have been applied to a collection of both male and female adult murine brains ranging over 4 strains and 6 neurologic knockout models. This collection and acquisition methods are now available to the neuroscience community as a standard web-deliverable service.

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Magnetic resonance histology for morphologic phenotyping

Cited by 112 publications

References 14 publications

Behavioral and Neuroanatomical Phenotypes in Mouse Models of Autism

Behavioral and Neuroanatomical Phenotypes in Mouse Models of Autism

Contribution of Magnetic Resonance Microscopy in the 12-Week Neurotoxicity Evaluation of Carbonyl Sulfide in Fischer 344 Rats

High-throughput morphologic phenotyping of the mouse brain with magnetic resonance histology

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