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High-resolution magnetic resonance histology of the embryonic and neonatal mouse: a 4D atlas and morphologic database.

ABSTRACT: Engineered mice play an ever-increasing role in defining connections between genotype and phenotypic expression. The potential of magnetic resonance microscopy (MRM) for morphologic phenotyping in the mouse has previously been demonstrated; however, applications have been limited by long scan times, availability of the technology, and a foundation of normative data. This article describes an integrated environment for high-resolution study of normal, transgenic, and mutant mouse models at embryonic and neonatal stages. Three-dimensional images are shown at an isotropic resolution of 19.5 microm (voxel volumes of 8 pL), acquired in 3 h at embryonic days 10.5-19.5 (10 stages) and postnatal days 0-32 (6 stages). A web-accessible atlas encompassing this data was developed, and for critical stages of embryonic development (prenatal days 14.5-18.5), >200 anatomical structures have been identified and labeled. Also, matching optical histology and analysis tools are provided to compare multiple specimens at multiple developmental stages. The utility of the approach is demonstrated in characterizing cardiac septal defects in conditional mutant embryos lacking the Smoothened receptor gene. Finally, a collaborative paradigm is presented that allows sharing of data across the scientific community. This work makes magnetic resonance microscopy of the mouse embryo and neonate broadly available with carefully annotated normative data and an extensive environment for collaborations.

SUBMITTER: Petiet AE

PROVIDER: S-EPMC2527911 | biostudies-literature | 2008 Aug

REPOSITORIES: biostudies-literature

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High-resolution magnetic resonance histology of the embryonic and neonatal mouse: a 4D atlas and morphologic database.

Petiet Alexandra E AE Kaufman Matthew H MH Goddeeris Matthew M MM Brandenburg Jeffrey J Elmore Susan A SA Johnson G Allan GA

Proceedings of the National Academy of Sciences of the United States of America 20080819 34

Engineered mice play an ever-increasing role in defining connections between genotype and phenotypic expression. The potential of magnetic resonance microscopy (MRM) for morphologic phenotyping in the mouse has previously been demonstrated; however, applications have been limited by long scan times, availability of the technology, and a foundation of normative data. This article describes an integrated environment for high-resolution study of normal, transgenic, and mutant mouse models at embryo ...[more]

PMID: 18713865

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Project description:Numerous shown consequences of age-related hearing loss have been unveiled; however, the relationship of the cortical and subcortical structures of the auditory pathway with aging is not well known. Investigations into neural structure analysis remain sparse due to difficulties of doing so in animal models; however, recent technological advances have been able to achieve a resolution adequate to perform such studies even in the small mouse. We utilize 12 members of the BXD family of recombinant inbred mice and aged separate cohorts. Utilizing novel magnetic resonance histology imaging techniques, we imaged these mice and generated high spatial resolution three dimensional images which were then comprehensively labeled. We completed volumetric analysis of 12 separate regions of interest specific to the auditory pathway brainstem nuclei and cortical areas with focus on the effect of aging upon said structures. Our results showed significant interstrain variation in the age-related effect on structure volume supporting a genetic influence in this interaction. Through multivariable modeling, we observed heterogenous effects of aging between different structures. Six of the 12 regions of interests demonstrated a significant age-related effect. The auditory cortex and ventral cochlear nucleus were found to decrease in volume with age, while the medial division of the medial geniculate nucleus, lateral lemniscus and its nucleus, and the inferior colliculus increased in size with age. Additionally, no sex-based differences were noted, and we observed a negative relationship between auditory cortex volume and mouse weight. This study is one of the first to perform comprehensive magnetic resonance imaging and quantitative analysis in the mouse brain auditory pathway cytoarchitecture, offering both novel insights into the neuroanatomical basis of age-related changes in hearing as well as evidence toward a genetic influence in this interaction. High resonance magnetic resonance imaging provides a promising efficacious avenue in future mouse model hearing loss investigations.

Project description:ObjectivesThe aim of this study was to develop and verify a method to obtain good temporal resolution T2-weighted 4-dimensional (4D-T2w) magnetic resonance imaging (MRI) by using motion information from T1-weighted 4D (4D-T1w) MRI, to support treatment planning in MR-guided radiotherapy.Materials and methodsTen patients with primary non-small cell lung cancer were scanned at 1.5 T axially with a volumetric T2-weighted turbo spin echo sequence gated to exhalation and a volumetric T1-weighted stack-of-stars spoiled gradient echo sequence with golden angle spacing acquired in free breathing. From the latter, 20 respiratory phases were reconstructed using the recently developed 4D joint MoCo-HDTV algorithm based on the self-gating signal obtained from the k-space center. Motion vector fields describing the respiratory cycle were obtained by deformable image registration between the respiratory phases and projected onto the T2-weighted image volume. The resulting 4D-T2w volumes were verified against the 4D-T1w volumes: an edge-detection method was used to measure the diaphragm positions; the locations of anatomical landmarks delineated by a radiation oncologist were compared and normalized mutual information was calculated to evaluate volumetric image similarity.ResultsHigh-resolution 4D-T2w MRI was obtained. Respiratory motion was preserved on calculated 4D-T2w MRI, with median diaphragm positions being consistent with less than 6.6 mm (2 voxels) for all patients and less than 3.3 mm (1 voxel) for 9 of 10 patients. Geometrical positions were coherent between 4D-T1w and 4D-T2w MRI as Euclidean distances between all corresponding anatomical landmarks agreed to within 7.6 mm (Euclidean distance of 2 voxels) and were below 3.8 mm (Euclidean distance of 1 voxel) for 355 of 470 pairs of anatomical landmarks. Volumetric image similarity was commensurate between 4D-T1w and 4D-T2w MRI, as mean percentage differences in normalized mutual information (calculated over all respiratory phases and patients), between corresponding respiratory phases of 4D-T1w and 4D-T2w MRI and the tie-phase of 4D-T1w and 3-dimensional T2w MRI, were consistent to 0.41% ± 0.37%. Four-dimensional T2w MRI displayed tumor extent, structure, and position more clearly than corresponding 4D-T1w MRI, especially when mobile tumor sites were adjacent to organs at risk.ConclusionsA methodology to obtain 4D-T2w MRI that retrospectively applies the motion information from 4D-T1w MRI to 3-dimensional T2w MRI was developed and verified. Four-dimensional T2w MRI can assist clinicians in delineating mobile lesions that are difficult to define on 4D-T1w MRI, because of poor tumor-tissue contrast.

Dataset Information

High-resolution magnetic resonance histology of the embryonic and neonatal mouse: a 4D atlas and morphologic database.

Publications

High-resolution magnetic resonance histology of the embryonic and neonatal mouse: a 4D atlas and morphologic database.

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