The SIGMA rat brain templates and atlases for multimodal MRI data analysis and visualization

AbstractPreclinical 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 $${\mathrm{T}}_2^ \ast$$T2*-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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Neurochemical and Pharmacological Properties of Tianeptine, A Novel Antidepressant

The British Journal of Psychiatry ◽

10.1192/s0007125000296694 ◽

1992 ◽

Vol 160 (S15) ◽

pp. 56-60 ◽

Cited By ~ 25

Author(s):

C. Labrid ◽

E. Mocaër ◽

A. Kamoun

Keyword(s):

Rat Brain ◽

Ex Vivo ◽

Animal Experiments ◽

Pyramidal Cells ◽

Human Platelets ◽

Clinical Findings ◽

Tricyclic Antidepressant ◽

Laboratory Animals ◽

5 Ht Uptake

Tianeptine is a tricyclic antidepressant with an unusual chemical structure (a long lateral chain grafted on to a substituted dibenzothiazepin nucleus), and with biochemical and animal-behavioural properties which are strikingly different from those of classical tricyclics. Unlike the latter, which decrease serotonin (5-HT) uptake, acute and chronic tianeptine treatment enhances 5-HT uptake in rat brain and in rat and human platelets ex vivo. In vivo, tianeptine potentiates the depletion of rat brain 5-HT by 4-methyl-alpha-ethyl metatyramine and increases rat hippocampal 5-HIAA; 5-HT uptake inhibitors (e.g. fluoxetine) have opposite effects. On iontophoretic injection into CA1 pyramidal cells, tianeptine shortens the period of neuronal hypoactivity caused by GABA or 5-HT, whereas other tricyclics prolong it, and it enhances attention, learning, and memory in laboratory animals, while classical tricyclics have opposite effects. However, the relationships between these effects of tianeptine in animal experiments and their relevance to clinical findings remain to be determined.

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Regional distribution of SGLT activity in rat brain in vivo

AJP Cell Physiology ◽

10.1152/ajpcell.00317.2012 ◽

2013 ◽

Vol 304 (3) ◽

pp. C240-C247 ◽

Cited By ~ 51

Author(s):

Amy S. Yu ◽

Bruce A. Hirayama ◽

Gerald Timbol ◽

Jie Liu ◽

Ana Diez-Sampedro ◽

...

Keyword(s):

Rat Brain ◽

Ex Vivo ◽

Osmotic Shock ◽

Regional Distribution ◽

The Body ◽

Specific Substrate ◽

Ex Vivo Autoradiography ◽

Molecular Imaging Probe ◽

The Brain

Na+-glucose cotransporter (SGLT) mRNAs have been detected in many organs of the body, but, apart from kidney and intestine, transporter expression, localization, and functional activity, as well as physiological significance, remain elusive. Using a SGLT-specific molecular imaging probe, α-methyl-4-deoxy-4-[18F]fluoro-d-glucopyranoside (Me-4-FDG) with ex vivo autoradiography and immunohistochemistry, we mapped in vivo the regional distribution of functional SGLTs in rat brain. Since Me-4-FDG is not a substrate for GLUT1 at the blood-brain barrier (BBB), in vivo delivery of the probe into the brain was achieved after opening of the BBB by an established procedure, osmotic shock. Ex vivo autoradiography showed that Me-4-FDG accumulated in regions of the cerebellum, hippocampus, frontal cortex, caudate nucleus, putamen, amygdala, parietal cortex, and paraventricular nucleus of the hypothalamus. Little or no Me-4-FDG accumulated in the brain stem. The regional accumulation of Me-4-FDG overlapped the distribution of SGLT1 protein detected by immunohistochemistry. In summary, after the BBB is opened, the specific substrate for SGLTs, Me-4-FDG, enters the brain and accumulates in selected regions shown to express SGLT1 protein. This localization and the sensitivity of these neurons to anoxia prompt the speculation that SGLTs may play an essential role in glucose utilization under stress such as ischemia. The expression of SGLTs in the brain raises questions about the potential effects of SGLT inhibitors under development for the treatment of diabetes.

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Volumetric assessment and longitudinal changes of brain structures in formalinized Beagle brains

10.1101/2021.12.03.471167 ◽

2021 ◽

Author(s):

Francesca Del Signore ◽

Germain Arribarat ◽

Leonardo Della Salda ◽

Giovanni Mogicato ◽

Alexandra Deviers ◽

...

Keyword(s):

Ex Vivo ◽

Brain Mri ◽

Brain Structures ◽

Formalin Fixation ◽

Post Mortem ◽

Intrinsic Variability ◽

Advanced Technique ◽

Longitudinal Changes ◽

Beagle Dog ◽

Volumetric Assessment

AbstractHigh field MRI represents an advanced technique both for diagnostic and research purposes on animal models such as the Beagle dog. The increasing interest in non-invasive neuroscience, aging, and neuropathological research led to a need of reference values (in terms of volumetric assessment) for the typical brain structures involved and, nowadays, several canine brain MRI atlases have been provided. Since no reports are available regarding the measurements reproducibility and few information are available about formalin fixation effect on brain structures when applied to MRI segmentation, we assessed the segmentation variability of selected structures as a function of the operator (two operators segmented the same data) and their intrinsic variability within a sample of 11 Beagle dogs (9 females and 2 males, 1.6 ± 0.2 years). Then, we analyzed for one further Beagle dog (2 years old) the longitudinal changes in the brain segmentations of these structures corresponding four conditions: in vivo, post mortem (after euthanasia), ex vivo (brain extracted and studied after 1 month in formalin and after 11 months); all the MRI images were collected with a 3 T MRI scanner. Our findings suggest that the segmentation procedure can be considered overall reproducible since only slight statistical differences were detected, apart from the ventricles.Furthermore, in the post mortem/ ex vivo comparison, the majority of the structures showed a higher contrast leading to more reproducible segmentations across operators and a net increase of volume of the studied structures; this could be justified by the intrinsic relaxation time changes observed as a consequence of formalin fixation, that led to an improvement of brain structures visualization and then segmentation.To conclude, MRI based segmentation seems to be a useful and accurate tool that allows longitudinal studies, especially when applied to formalin fixed brains.

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Abstract 474: Early Events in Dissecting Aneurysms Induced by Angiotensin-II Infusion: The Geometry-Driven Aspect of a Multifaceted Problem

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvb.37.suppl_1.474 ◽

2017 ◽

Vol 37 (suppl_1) ◽

Author(s):

Lydia Aslanidou ◽

Bram Trachet ◽

Mauro Ferraro ◽

Alessandra Piersigilli ◽

Rodrigo Fraga-Silva ◽

...

Keyword(s):

Finite Element ◽

Angiotensin Ii ◽

Ex Vivo ◽

Apoptotic Cell ◽

Morphological Changes ◽

Aortic Tissue ◽

Isotropic Resolution ◽

Circumferential Distribution ◽

Dissecting Aneurysms

While research on dissecting aneurysms in Angiotensin-II infused mice spans more than a decade, the temporal sequence of initial events still remains unclear. Recent findings in our group suggested that focal medial tears at the vicinity of suprarenal side branches are the primary event in disease formation. In this study we used a combined experimental-computational approach to investigate the hypothesis that initial events of dissecting AAAs originate at branching sites along the aorta. Male apolipoprotein-deficient mice were infused with Angiotensin-II (n=11) and saline 0.9% (n=6) for 3 days and scanned with contrast-enhanced microCT prior to sacrifice. One animal presented an in-vivo rupture during the microCT scan, and was rescanned after 2.5 hours to observe real-time morphological changes. In all other animals, the excised aortic tissue was imaged with Phase Contrast X-Ray Tomographic Microscopy (PCXTM) at 6.5um isotropic resolution. An automatic morphing code was developed to map the ex-vivo geometry onto the in vivo geometry, and a finite element simulation yielded a stress distribution that represents an estimation of the wall tension, not only due to the pressurization, but also due to the local stretch field. We found that the nanoparticulate microCT contrast agent had infiltrated the aortic wall in 11/11 Ang-II infused animals, while no infiltration was observed in 6/6 control mice. The infiltration affected at least one pair of intercostal arteries in 11/11 mice, and in 9/11 mice the coeliac region was also affected. Image-guided histology allowed us to determine the circumferential distribution of microlesions at branching sites, including disruption of elastin fibers, apoptotic cell appearance, subintimal leukocyte infiltration and intramural hematomas. In the animal whose aorta had ruptured during the in vivo scan, the initial hematoma had originated around 3 pairs of intercostal arteries and quickly propagated afterwards. Mouse-specific finite element simulations revealed a co-location of computed peak stresses at the vessel wall and histologically identified vascular damage. We conclude that the aortic geometry, and side branches in particular, play a pivotal role in the onset of dissecting AAA.

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Comparison of in vivo and ex vivo [3H]flumazenil binding assays to determine occupancy at the benzodiazepine binding site of rat brain GABAA receptors

Neuropharmacology ◽

10.1016/j.neuropharm.2006.03.020 ◽

2006 ◽

Vol 51 (1) ◽

pp. 168-172 ◽

Cited By ~ 28

Author(s):

Jennifer Li ◽

Rebecca L. Fish ◽

Susan M. Cook ◽

Frederick D. Tattersall ◽

John R. Atack

Keyword(s):

Binding Site ◽

Rat Brain ◽

Gabaa Receptors ◽

Ex Vivo ◽

Binding Assays ◽

Benzodiazepine Binding

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Navigator-Free Submillimeter Diffusion Imaging Using Multishot-Encoded Simultaneous Multi-Slice (MUSIUM)

10.21203/rs.3.rs-131073/v1 ◽

2020 ◽

Author(s):

Wei-Tang Chang ◽

Khoi Huynh ◽

Pew-Thian Yap ◽

Weili Lin

Keyword(s):

Signal To Noise Ratio ◽

Diffusion Imaging ◽

Brain Structures ◽

Peak Amplitude ◽

Acquisition Time ◽

Rf Power ◽

Isotropic Resolution ◽

Low Snr ◽

Scan Time

Abstract The ability to achieve submillimter isotropic resolution diffusion MR imaging (dMRI) is critically important to study fine-scale brain structures. One of the major challenges in submillimeter dMRI is the inherently low signal-to-noise ratio (SNR). While approaches capable of mitigating the low SNR have been proposed, namely simultaneous multi-slab (SMSlab) and generalized slice dithered enhanced resolution with simultaneous multislice (gSlider-SMS), limitations are associated with these approaches. The SMSlab sequences suffer from the slab boundary artifacts and require additional navigators for phase estimation. On the other hand, gSlider sequences require relatively high RF power and peak amplitude, which increase the SAR and complicate the RF excitation. In this work, we developed a navigator-free multishot-encoded simultaneous multi-slice (MUSIUM) imaging approach, achieving enhanced SNR, low RF power and peak amplitude, and being free from slab boundary artifacts. The dMRI with ultrahigh resolution (0.86 mm isotropic), whole brain coverage and ~12.5 minute acquisition time were achieved, revealing detailed structures at cortical and white matter areas. The simulated and in vivo results also demonstrated that the MUSIUM imaging was minimally affected by the motion. Taken together, the MUSIUM imaging is a promising approach to achieve submillimeter diffusion imaging on 3T scanner within clinically feasible scan time.

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Subcortical Atlas of the Rhesus Macaque (SARM) for Magnetic Resonance Imaging

10.1101/2020.09.16.300053 ◽

2020 ◽

Author(s):

Renée Hartig ◽

Daniel Glen ◽

Benjamin Jung ◽

Nikos K. Logothetis ◽

George Paxinos ◽

...

Keyword(s):

Magnetic Resonance Imaging ◽

Magnetic Resonance ◽

Rhesus Macaque ◽

Ex Vivo ◽

Brain Structures ◽

List Type ◽

Resonance Imaging ◽

Magnetic Resonance Imaging Mri ◽

Dorsal Lateral Geniculate

AbstractDigitized neuroanatomical atlases are crucial for localizing brain structures and analyzing functional networks identified by magnetic resonance imaging (MRI). To aid in MRI data analysis, we have created a comprehensive parcellation of the rhesus macaque subcortex using a high-resolution ex vivo structural imaging scan. The structural scan and its parcellation were warped to the updated NIMH Macaque Template (NMT v2), an in vivo population template, where the parcellation was refined to produce the Subcortical Atlas of the Rhesus Macaque (SARM). The subcortical parcellation and nomenclature reflect those of the 4th edition of the Rhesus Monkey Brain in Stereotaxic Coordinates (RMBSC4; Paxinos et al., in preparation). The SARM features six parcellation levels, arranged hierarchically from fine regions-of-interest (ROIs) to broader composite regions, suited for fMRI studies. As a test, we ran a functional localizer for the dorsal lateral geniculate (DLG) nucleus in three macaques and found significant fMRI activation in this atlas region. The SARM has been made openly available to the neuroimaging community and can easily be used with common MR data processing software, such as AFNI, where the atlas can be embedded into the software alongside cortical macaque atlases.HighlightsWe present the Subcortical Atlas of the Rhesus Macaque (SARM).SARM provides a neuroanatomical reference frame for neuroimaging analysis.The entire subcortex is mapped, including the thalamus, basal ganglia, and brainstem.ROIs are grouped hierarchically, making SARM useful at multiple spatial resolutions.SARM is in the NMT v2 template space and complements the CHARM atlas for the cortex.

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Preparation of Ex Vivo Rodent Phantoms for Developing, Testing, and Training MR Imaging of the Kidney and Other Organs

Methods in Molecular Biology - Preclinical MRI of the Kidney ◽

10.1007/978-1-0716-0978-1_5 ◽

2021 ◽

pp. 75-85

Author(s):

Jason M. Millward ◽

João S. Periquito ◽

Paula Ramos Delgado ◽

Christian Prinz ◽

Thoralf Niendorf ◽

...

Keyword(s):

Mr Imaging ◽

Ex Vivo ◽

In Vivo Studies ◽

The European Union ◽

Target Organs ◽

Preclinical Mri ◽

Renal Mri ◽

And Training

AbstractHere we describe a simple and inexpensive protocol for preparing ex vivo rodent phantoms for use in MR imaging studies. The experimental animals are perfused and fixed with formaldehyde, and then wrapped with gauze and sealed with liquid latex. This yields a phantom that preserves all organs in situ, and which avoids the need to keep fixed animals and organs in containers that have dimensions very different from living animals. This is especially important for loading in MR detectors, and specifically the RF coils, they are usually used with. The phantom can be safely stored and conveniently reused, and can provide MR scientists with a realistic phantom with which to establish protocols in preparation for preclinical in vivo studies—for renal, brain, and body imaging. The phantom also serves as an ideal teaching tool, for trainees learning how to perform preclinical MRI investigations of the kidney and other target organs, while avoiding the need for handling living animals, and reducing the total number of animals required.This protocol chapter is part of the PARENCHIMA initiative “MRI Biomarkers for CKD” (CA16103), a community-driven Action of the European Cooperation in Science and Technology (COST) program of the European Union, which aims to improve the reproducibility and standardization of renal MRI biomarkers.

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