B-Mode Ultrasound, a Reliable Tool for Monitoring Experimental Intracerebral Hemorrhage

Background: Magnetic resonance imaging (MRI) is currently used for the study of intracerebral hemorrhage (ICH) in animal models. However, ultrasound is an inexpensive, non-invasive and rapid technique that could facilitate the diagnosis and follow-up of ICH. This study aimed to evaluate the feasibility and reliability of B-mode ultrasound as an alternative tool for in vivo monitoring of ICH volume and brain structure displacement in an animal model.Methods: A total of 31 male and female Sprague-Dawley rats were subjected to an ICH model using collagenase-IV in the striatum following stereotaxic references. The animals were randomly allocated into 3 groups: healthy (n = 10), sham (n = 10) and ICH (n = 11). B-mode ultrasound studies with a 13-MHz probe were performed pre-ICH and at 5 h, 48 h, 4 d and 1 mo post-ICH for the assessment of ICH volume and displacement of brain structures, considering the distance between the subarachnoid cisterns and the dura mater. The same variables were studied by MRI at 48 h and 1 mo post-ICH.Results: Both imaging techniques showed excellent correlation in measuring ICH volume at 48 h (r = 0.905) and good at 1 mo (r = 0.656). An excellent correlation was also observed in the measured distance between the subarachnoid cisterns and the dura mater at 1 mo between B-mode ultrasound and MRI, on both the ipsilateral (r = 0.870) and contralateral (r = 0.906) sides of the lesion.Conclusion: B-mode ultrasound imaging appears to be a reliable tool for in vivo assessment of ICH volume and displacement of brain structures in animal models.

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Study of Osteocyte Behavior by High-Resolution Intravital Imaging Following Photo-Induced Ischemia

Molecules ◽

10.3390/molecules23112874 ◽

2018 ◽

Vol 23 (11) ◽

pp. 2874

Author(s):

Hengfeng Yuan ◽

Wen Jiang ◽

Yuanxin Chen ◽

Betty Kim

Keyword(s):

Imaging Techniques ◽

Avascular Osteonecrosis ◽

Functional Changes ◽

Cellular Processes ◽

Non Invasive ◽

Behavioral Dynamics ◽

Bony Anatomy ◽

Magnetic Resonance Imaging Mri

Ischemic injuries and local hypoxia can result in osteocytes dysfunction and play a key role in the pathogenesis of avascular osteonecrosis. Conventional imaging techniques including magnetic resonance imaging (MRI) and computed tomography (CT) can reveal structural and functional changes within bony anatomy; however, characterization of osteocyte behavioral dynamics in the setting of osteonecrosis at the single cell resolution is limited. Here, we demonstrate an optical approach to study real-time osteocyte functions in vivo. Using nicotinamide adenine dinucleotide (NADH) as a biomarker for metabolic dynamics in osteocytes, we showed that NADH level within osteocytes transiently increase significantly after local ischemia through non-invasive photo-induced thrombosis of afferent arterioles followed by a steady decline. Our study presents a non-invasive optical approach to study osteocyte behavior through the modulation of local environmental conditions. Thus it provides a powerful toolkit to study cellular processes involved in bone pathologies in vivo.

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Remote Corticospinal Tract Degeneration After Cortical Stroke in Rats May Not Preclude Spontaneous Sensorimotor Recovery

Neurorehabilitation and Neural Repair ◽

10.1177/15459683211041318 ◽

2021 ◽

pp. 154596832110413

Author(s):

Michel R. T. Sinke ◽

Geralda A. F. van Tilborg ◽

Anu E. Meerwaldt ◽

Caroline L. van Heijningen ◽

Annette van der Toorn ◽

...

Keyword(s):

Functional Connectivity ◽

Corticospinal Tract ◽

Sprague Dawley ◽

Post Stroke ◽

Neuronal Communication ◽

Cortical Stroke ◽

Magnetic Resonance Imaging Mri ◽

And Behavior ◽

Sensorimotor Recovery

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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In vivo imaging techniques: a new era for histochemical analysis

European Journal of Histochemistry ◽

10.4081/ejh.2016.2725 ◽

2016 ◽

Cited By ~ 6

Author(s):

A. Busato ◽

P. Fumene Feruglio ◽

P.P. Parnigotto ◽

P. Marzola ◽

A. Sbarbati

Keyword(s):

Magnetic Resonance ◽

In Vivo Imaging ◽

Diffusion Tensor ◽

Technological Development ◽

Imaging Techniques ◽

Resonance Spectroscopy ◽

Preclinical Research ◽

Tissue Contrast ◽

Magnetic Resonance Imaging Mri

In vivo imaging techniques can be integrated with classical histochemistry to create an actual histochemistry of water. In particular, Magnetic Resonance Imaging (MRI), an imaging technique primarily used as diagnostic tool in clinical/preclinical research, has excellent anatomical resolution, unlimited penetration depth and intrinsic soft tissue contrast. Thanks to the technological development, MRI is not only capable to provide morphological information but also and more interestingly functional, biophysical and molecular. In this paper we describe the main features of several advanced imaging techniques, such as MRI microscopy, Magnetic Resonance Spectroscopy, functional MRI, Diffusion Tensor Imaging and MRI with contrast agent as a useful support to classical histochemistry.

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Animal Models for imaging

Disease Markers ◽

10.1155/2002/760473 ◽

2002 ◽

Vol 18 (5-6) ◽

pp. 365-374 ◽

Cited By ~ 10

Author(s):

Barbara Y. Croft

Keyword(s):

Animal Models ◽

Human Disease ◽

Imaging Techniques ◽

Primary Model ◽

The Future ◽

Research Choices

Animal models can be used in the study of disease. This chapter discusses imaging animal models to elucidate the process of human disease. The mouse is used as the primary model. Though this choice simplifies many research choices, it necessitates compromises forin vivoimaging. In the future, we can expect improvements in both animal models and imaging techniques.

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Magnetic Resonance Imaging in Animal Models of Alzheimer’s Disease Amyloidosis

10.20944/preprints202110.0231.v1 ◽

2021 ◽

Author(s):

Ruiqing Ni

Keyword(s):

Magnetic Resonance Imaging ◽

Magnetic Resonance ◽

Animal Models ◽

Amyloid Beta ◽

High Field ◽

Diffusion Tensor ◽

Small Animal ◽

Resonance Imaging ◽

Magnetic Resonance Imaging Mri

Amyloid-beta plays an important role in the pathogenesis of Alzheimer’s disease. Aberrant amyloid-beta and tau accumulation induce neuroinflammation, cerebrovascular alterations, synaptic deficits, functional deficits, and neurodegeneration, leading to cognitive impairment. Animal models recapitulating the amyloid-beta pathology such as transgenic, knock-in mouse and rat models have facilitated the understanding of disease mechanisms and development of therapeutics targeting at amyloid-beta. There is a rapid advance in high-field MR in small animals. Versatile high-field magnetic resonance imaging (MRI) sequences such as diffusion tensor imaging, arterial spin labelling, resting-state functional MRI, anatomical MRI, MR spectroscopy as well as contrast agents have been developed for the applications in animal models. These tools have enabled high-resolution in vivo structural, functional, and molecular readouts with a whole brain field-of-view. MRI have been utilized to visualize non-invasively the amyloid-beta deposits, synaptic deficits, regional brain atrophy, impairment in white matter integrity, functional connectivity, cerebrovascular and glymphatic system in animal models of amyloidosis. Many of the readouts are translational in clinical MRI in the brain of patients with Alzheimer’s disease. In this review, we summarize the recent advance of using MRI for visualizing the pathophysiology in amyloidosis animal model. We discuss the outstanding challenges in brain imaging using MRI in small animal and propose future outlook in visualizing amyloid-beta-related alterations in brain of animal models.

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NLRP3 Inflammasome Activation Attenuates Neuronal Apoptosis by Upregulating Autophagy through AMPK/Beclin-1 Pathway after Intracerebral Hemorrhage with Ventricular Extension in Rats

10.21203/rs.3.rs-203453/v1 ◽

2021 ◽

Author(s):

Zhaoqi Zhang ◽

Peiwen Guo ◽

Zhengcai Jia ◽

Tunan Chen ◽

Hua Feng

Keyword(s):

Intracerebral Hemorrhage ◽

Nlrp3 Inflammasome ◽

Neuronal Apoptosis ◽

Specific Inhibitor ◽

Beclin 1 ◽

Tunel Staining ◽

Inflammasome Activation ◽

Sprague Dawley

Abstract BackgroundIn brain, NLRP3 inflammasome, mainly derived from macrophage/microglia, is involved in proinflammatory and neurodeficits after hemorrhage, and autophagy is vital for neuronal homeostasis and functions. Accumulating evidence suggested that NLRP3 inflammasome and autophagy played an important role in intracerebral hemorrhage (ICH). Thus, this study was designed to further explore the pathogenesis of neurodeficits after in posthemorrhagic hydrocephalus.MethodsAutologous blood injection model was induced to mimic ICH with ventricular extension (ICH-IVH) in Sprague-Dawley rats. To elucidate the underlying mechanism, the NLRP3 inflammasome inhibitor MCC950 was administered abdominally at 1 h after ICH-IVH. Magnetic resonance imaging, neurobehavioral tests, immunofluorescence, western blotting, Fluoro-Jade C- staining, Tunel staining, and Quantitative RNA Sequencing were performed.ResultsIn the acute phase of ICH-IVH, both the expression of NLRP3 inflammasome and the autophagy of neurons were upregulated. The activated NLRP3 in macrophage/microglia promoted the release of IL-1β to extracellular, which contributed to excessive autophagy, leading to neurons apoptosis both in vivo and in vitro. AMPK/Beclin-1 pathway played an important role in NLRP3-related neurons autophagy. Using MCC950(NLRP3 inflammasome specific inhibitor) treatment after ICH-IVH significantly reduced ventricles dilation, improved neurofunction, down-regulated the release of IL-1β, and alleviated neuroinflammation and excessive autophagy.ConclusionsOur finding demonstrated that NLRP3 inflammasome activated in microglia/macrophage aggravated neurological outcomes and neuronal apoptosis by upregulating autophagy after ICH-IVH, which was partly mediated by the AMPK/Beclin-1 pathway. Therefore, inhibiting the activation of NLRP3 may be a potential therapeutic strategy for the neurodeficits of ICH-IVH patients.

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New chemical biopsy tool for spatially resolved profiling of human brain tissue in vivo

Scientific Reports ◽

10.1038/s41598-021-98973-y ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Joanna Bogusiewicz ◽

Katarzyna Burlikowska ◽

Kamil Łuczykowski ◽

Karol Jaroch ◽

Marcin Birski ◽

...

Keyword(s):

Human Brain ◽

Grey Matter ◽

Solid Phase ◽

Imaging Techniques ◽

Brain Structures ◽

Limited Information ◽

Human Brain Tissue ◽

Sampling Device ◽

Spatially Resolved

AbstractIt is extremely challenging to perform chemical analyses of the brain, particularly in humans, due to the restricted access to this organ. Imaging techniques are the primary approach used in clinical practice, but they only provide limited information about brain chemistry. Solid-phase microextraction (SPME) has been presented recently as a chemical biopsy tool for the study of animal brains. The current work demonstrates for the first time the use of SPME for the spatially resolved sampling of the human brain in vivo. Specially designed multi-probe sampling device was used to simultaneously extract metabolites from the white and grey matter of patients undergoing brain tumor biopsies. Samples were collected by inserting the probes along the planned trajectory of the biopsy needle prior to the procedure, which was followed by metabolomic and lipidomic analyses. The results revealed that studied brain structures were predominantly composed of lipids, while the concentration and diversity of detected metabolites was higher in white than in grey matter. Although the small number of participants in this research precluded conclusions of a biological nature, the results highlight the advantages of the proposed SPME approach, as well as disadvantages that should be addressed in future studies.

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Evaluating the In Vivo Specificity of [18F]UCB-H for the SV2A Protein, Compared with SV2B and SV2C in Rats Using microPET

Molecules ◽

10.3390/molecules24091705 ◽

2019 ◽

Vol 24 (9) ◽

pp. 1705 ◽

Cited By ~ 3

Author(s):

Maria Elisa Serrano ◽

Guillaume Becker ◽

Mohamed Ali Bahri ◽

Alain Seret ◽

Nathalie Mestdagh ◽

...

Keyword(s):

Synaptic Vesicle ◽

Brain Structures ◽

Input Function ◽

Population Based ◽

The Other ◽

Sprague Dawley ◽

Logan Plot ◽

Sprague Dawley Rats ◽

Inferior Colliculi

The synaptic vesicle protein 2 (SV2) is involved in synaptic vesicle trafficking. The SV2A isoform is the most studied and its implication in epilepsy therapy led to the development of the first SV2A PET radiotracer [18F]UCB-H. The objective of this study was to evaluate in vivo, using microPET in rats, the specificity of [18F]UCB-H for SV2 isoform A in comparison with the other two isoforms (B and C) through a blocking assay. Twenty Sprague Dawley rats were pre-treated either with the vehicle, or with specific competitors against SV2A (levetiracetam), SV2B (UCB5203) and SV2C (UCB0949). The distribution volume (Vt, Logan plot, t* 15 min) was obtained with a population-based input function. The Vt analysis for the entire brain showed statistically significant differences between the levetiracetam group and the other groups (p < 0.001), but also between the vehicle and the SV2B group (p < 0.05). An in-depth Vt analysis conducted for eight relevant brain structures confirmed the statistically significant differences between the levetiracetam group and the other groups (p < 0.001) and highlighted the superior and the inferior colliculi along with the cortex as regions also displaying statistically significant differences between the vehicle and SV2B groups (p < 0.05). These results emphasize the in vivo specificity of [18F]UCB-H for SV2A against SV2B and SV2C, confirming that [18F]UCB-H is a suitable radiotracer for in vivo imaging of the SV2A proteins with PET.

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Early detection of doxorubicin-induced cardiotoxicity in rats by its cardiac metabolic signature assessed with hyperpolarized MRI

Communications Biology ◽

10.1038/s42003-020-01440-z ◽

2020 ◽

Vol 3 (1) ◽

Cited By ~ 1

Author(s):

Kerstin N. Timm ◽

Charith Perera ◽

Vicky Ball ◽

John A. Henry ◽

Jack J. Miller ◽

...

Keyword(s):

Mitochondrial Dysfunction ◽

Real Time ◽

Chemotherapeutic Agent ◽

Imaging Techniques ◽

Functional Decline ◽

Metabolic Fluxes ◽

Key Factor ◽

Hyperpolarized Mri ◽

Magnetic Resonance Imaging Mri

AbstractDoxorubicin (DOX) is a widely used chemotherapeutic agent that can cause serious cardiotoxic side effects culminating in congestive heart failure (HF). There are currently no clinical imaging techniques or biomarkers available to detect DOX-cardiotoxicity before functional decline. Mitochondrial dysfunction is thought to be a key factor driving functional decline, though real-time metabolic fluxes have never been assessed in DOX-cardiotoxicity. Hyperpolarized magnetic resonance imaging (MRI) can assess real-time metabolic fluxes in vivo. Here we show that cardiac functional decline in a clinically relevant rat-model of DOX-HF is preceded by a change in oxidative mitochondrial carbohydrate metabolism, measured by hyperpolarized MRI. The decreased metabolic fluxes were predominantly due to mitochondrial loss and additional mitochondrial dysfunction, and not, as widely assumed hitherto, to oxidative stress. Since hyperpolarized MRI has been successfully translated into clinical trials this opens up the potential to test cancer patients receiving DOX for early signs of cardiotoxicity.

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Advances in spinal cord imaging in multiple sclerosis

Therapeutic Advances in Neurological Disorders ◽

10.1177/1756286419840593 ◽

2019 ◽

Vol 12 ◽

pp. 175628641984059 ◽

Cited By ~ 16

Author(s):

Marcello Moccia ◽

Serena Ruggieri ◽

Antonio Ianniello ◽

Ahmed Toosy ◽

Carlo Pozzilli ◽

...

Keyword(s):

Multiple Sclerosis ◽

Spinal Cord ◽

Imaging Techniques ◽

Quantitative Imaging ◽

Automated Analysis ◽

Spinal Cord Atrophy ◽

Recent Developments ◽

Magnetic Resonance Imaging Mri ◽

Spinal Cord Imaging

The spinal cord is frequently affected in multiple sclerosis (MS), causing motor, sensory and autonomic dysfunction. A number of pathological abnormalities, including demyelination and neuroaxonal loss, occur in the MS spinal cord and are studied in vivo with magnetic resonance imaging (MRI). The aim of this review is to summarise and discuss recent advances in spinal cord MRI. Advances in conventional spinal cord MRI include improved identification of MS lesions, recommended spinal cord MRI protocols, enhanced recognition of MRI lesion characteristics that allow MS to be distinguished from other myelopathies, evidence for the role of spinal cord lesions in predicting prognosis and monitoring disease course, and novel post-processing methods to obtain lesion probability maps. The rate of spinal cord atrophy is greater than that of brain atrophy (−1.78% versus −0.5% per year), and reflects neuroaxonal loss in an eloquent site of the central nervous system, suggesting that it can become an important outcome measure in clinical trials, especially in progressive MS. Recent developments allow the calculation of spinal cord atrophy from brain volumetric scans and evaluation of its progression over time with registration-based techniques. Fully automated analysis methods, including segmentation of grey matter and intramedullary lesions, will facilitate the use of spinal cord atrophy in trial designs and observational studies. Advances in quantitative imaging techniques to evaluate neuroaxonal integrity, myelin content, metabolic changes, and functional connectivity, have provided new insights into the mechanisms of damage in MS. Future directions of research and the possible impact of 7T scanners on spinal cord imaging will be discussed.

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