Merged magnetic resonance and light sheet microscopy of the whole mouse brain.

We have developed workflows to align 3D magnetic resonance histology (MRH) of the mouse brain with light sheet microscopy (LSM) and 3D delineations of the same specimen. We start with MRH of the brain in the skull with gradient echo and diffusion tensor imaging (DTI) at 15 μm isotropic resolution which is ~ higher than that of most preclinical MRI. Connectomes are generated with superresolution tract density images of ~5 μm.

Volumetric analysis of the aging auditory pathway using high resolution magnetic resonance histology.

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.

Prenatal heroin exposure alters brain morphology and connectivity in adolescent mice.

The United States is experiencing a dramatic increase in maternal opioid misuse and, consequently, the number of individuals exposed to opioids in utero. Prenatal opioid exposure has both acute and long-lasting effects on health and wellbeing. Effects on the brain, often identified at school age, manifest as cognitive impairment, attention deficit, and reduced scholastic achievement.

Tractography of Porcine Meniscus Microstructure Using High-Resolution Diffusion Magnetic Resonance Imaging.

To noninvasively evaluate the three-dimensional collagen fiber architecture of porcine meniscus using diffusion MRI, meniscal specimens were scanned using a 3D diffusion-weighted spin-echo pulse sequence at 7.0 T. The collagen fiber alignment was revealed in each voxel and the complex 3D collagen network was visualized for the entire meniscus using tractography.

Resolution and b value dependent structural connectome in ex vivo mouse brain.

Diffusion magnetic resonance imaging has been widely used in both clinical and preclinical studies to characterize tissue microstructure and structural connectivity. The diffusion MRI protocol for the Human Connectome Project (HCP) has been developed and optimized to obtain high-quality, high-resolution diffusion MRI (dMRI) datasets. However, such efforts have not been fully explored in preclinical studies, especially for rodents.

A time-course study of actively stained mouse brains: Diffusion tensor imaging parameters and connectomic stability over 1 year.

While the application of diffusion tensor imaging (DTI), tractography, and connectomics to fixed tissue is a common practice today, there have been limited studies examining the effects of fixation on brain microstructure over extended periods. This mouse model time-course study reports the changes of regional brain volumes and diffusion scalar parameters, such as fractional anisotropy, across 12 representative brain regions as measures of brain structural stability. The scalar DTI parameters and regional volumes were highly variable over the first 2 weeks after fixation.

A multicontrast MR atlas of the Wistar rat brain.

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/mm 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.

Ex Vivo MR Histology and Cytometric Feature Mapping Connect Three-dimensional in Vivo MR Images to Two-dimensional Histopathologic Images of Murine Sarcomas.

Purpose To establish a platform for quantitative tissue-based interpretation of cytoarchitecture features from tumor MRI measurements. Materials and Methods In a pilot preclinical study, multicontrast in vivo MRI of murine soft-tissue sarcomas in 10 mice, followed by ex vivo MRI of fixed tissues (termed ), was performed. Paraffin-embedded limb cross-sections were stained with hematoxylin-eosin, digitized, and registered with MRI.

Mapping the peripheral nervous system in the whole mouse via compressed sensing tractography.

The peripheral nervous system (PNS) connects the central nervous system with the rest of the body to regulate many physiological functions and is therapeutically targeted to treat diseases such as epilepsy, depression, intestinal dysmotility, chronic pain, and more. However, we still lack understanding of PNS innervation in most organs because the large span, diffuse nature, and small terminal nerve bundle fibers have precluded whole-organism, high resolution mapping of the PNS. We sought to produce a comprehensive peripheral nerve atlas for use in future interrogation of neural circuitry and selection of targets for neuromodulation.

A high-resolution interactive atlas of the human brainstem using magnetic resonance imaging.

Conventional atlases of the human brainstem are limited by the inflexible, sparsely-sampled, two-dimensional nature of histology, or the low spatial resolution of conventional magnetic resonance imaging (MRI). Postmortem high-resolution MRI circumvents the challenges associated with both modalities. A single human brainstem specimen extending from the rostral diencephalon through the caudal medulla was prepared for imaging after the brain was removed from a 65-year-old male within 24 h of death.

Optimizing Diffusion Imaging Protocols for Structural Connectomics in Mouse Models of Neurological Conditions.

Network approaches provide sensitive biomarkers for neurological conditions, such as Alzheimer's disease (AD). Mouse models can help advance our understanding of underlying pathologies, by dissecting vulnerable circuits. While the mouse brain contains less white matter compared to the human brain, axonal diameters compare relatively well (e.

Microcephaly with altered cortical layering in GIT1 deficiency revealed by quantitative neuroimaging.

G Protein-Coupled Receptor Kinase-Interacting Protein-1 (GIT1) regulates neuronal functions, including cell and axon migration and synapse formation and maintenance, and GIT1 knockout (KO) mice exhibit learning and memory deficits. We noted that male and female GIT1-KO mice exhibit neuroimaging phenotypes including microcephaly, and altered cortical layering, with a decrease in neuron density in cortical layer V. Micro-CT and magnetic resonance microscopy (MRM) were used to identify morphometric phenotypes for the skulls and throughout the GIT1-KO brains.

Cytoarchitecture of the mouse brain by high resolution diffusion magnetic resonance imaging.

MRI has been widely used to probe the neuroanatomy of the mouse brain, directly correlating MRI findings to histology is still challenging due to the limited spatial resolution and various image contrasts derived from water relaxation or diffusion properties. Magnetic resonance histology has the potential to become an indispensable research tool to mitigate such challenges. In the present study, we acquired high spatial resolution MRI datasets, including diffusion MRI (dMRI) at 25 ​μm isotropic resolution and quantitative susceptibility mapping (QSM) at 21.

Characterization complex collagen fiber architecture in knee joint using high-resolution diffusion imaging.

Purpose: To evaluate the complex fiber orientations and 3D collagen fiber network of knee joint connective tissues, including ligaments, muscle, articular cartilage, and meniscus using high spatial and angular resolution diffusion imaging.

Methods: Two rat knee joints were scanned using a modified 3D diffusion-weighted spin echo pulse sequence with the isotropic spatial resolution of 45 μm at 9.4T.

Neurite orientation dispersion and density imaging of mouse brain microstructure.

Advanced biophysical models like neurite orientation dispersion and density imaging (NODDI) have been developed to estimate the microstructural complexity of voxels enriched in dendrites and axons for both in vivo and ex vivo studies. NODDI metrics derived from high spatial and angular resolution diffusion MRI using the fixed mouse brain as a reference template have not yet been reported due in part to the extremely long scan time required. In this study, we modified the three-dimensional diffusion-weighted spin-echo pulse sequence for multi-shell and undersampling acquisition to reduce the scan time.

Diffusion tractography of the rat knee at microscopic resolution.

Purpose: To evaluate whole knee joint tractography, including articular cartilage, ligaments, meniscus, and growth plate using diffusion tensor imaging (DTI) at microscopic resolution.

Methods: Three rat knee joints were scanned using a modified 3D diffusion-weighted spin echo pulse sequence with 90- and 45-μm isotropic spatial resolution at 9.4T.

Accelerating quantitative susceptibility imaging acquisition using compressed sensing.

To evaluate the feasibility of compressed sensing (CS) for accelerating quantitative susceptibility mapping (QSM) acquisition in MR histology, control, demyelination, and remyelination mice were scanned using a modified 3D gradient echo (GRE) pulse sequence (allowing undersampling the k-space in two phase dimensions) at 9.4 T. Fully sampled and CS data at various acceleration factors (AF) (4.

Whole mouse brain connectomics.

Methods have been developed to allow quantitative connectivity of the whole fixed mouse brain by means of magnetic resonance imaging (MRI). We have translated what we have learned in clinical imaging to the very special domain of the mouse brain. Diffusion tensor imaging (DTI) of perfusion fixed specimens can now be performed with spatial resolution of 45 μm , that is, voxels that are 21,000 times smaller than the human connectome protocol.

Whole mouse brain structural connectomics using magnetic resonance histology.

Diffusion tensor histology holds great promise for quantitative characterization of structural connectivity in mouse models of neurological and psychiatric conditions. There has been extensive study in both the clinical and preclinical domains on the complex tradeoffs between the spatial resolution, the number of samples in diffusion q-space, scan time, and the reliability of the resultant data. We describe here a method for accelerating the acquisition of diffusion MRI data to support quantitative connectivity measurements in the whole mouse brain using compressed sensing (CS).

Postmortem diffusion MRI of the entire human spinal cord at microscopic resolution.

The human spinal cord is a central nervous system structure that plays an important role in normal motor and sensory function, and can be affected by many debilitating neurologic diseases. Due to its clinical importance, the spinal cord is frequently the subject of imaging research. Common methods for visualizing spinal cord anatomy and pathology include histology and magnetic resonance imaging (MRI), both of which have unique benefits and drawbacks.

Diffusion tensor imaging using multiple coils for mouse brain connectomics.

The correlation between brain connectivity and psychiatric or neurological diseases has intensified efforts to develop brain connectivity mapping techniques on mouse models of human disease. The neural architecture of mouse brain specimens can be shown non-destructively and three-dimensionally by diffusion tensor imaging, which enables tractography, the establishment of a connectivity matrix and connectomics. However, experiments on cohorts of animals can be prohibitively long.

Susceptibility tensor imaging and tractography of collagen fibrils in the articular cartilage.

Purpose: To investigate the B orientation-dependent magnetic susceptibility of collagen fibrils within the articular cartilage and to determine whether susceptibility tensor imaging (STI) can detect the 3D collagen network within cartilage.

Methods: Multiecho gradient echo datasets (100-μm isotropic resolution) were acquired from fixed porcine articular cartilage specimens at 9.4 T.