scholarly journals In Vivo Detection of Cerebral Cortical Microinfarcts with High-Resolution 7T MRI

2012 ◽  
Vol 33 (3) ◽  
pp. 322-329 ◽  
Author(s):  
Susanne J van Veluw ◽  
Jaco JM Zwanenburg ◽  
JooYeon Engelen-Lee ◽  
Wim GM Spliet ◽  
Jeroen Hendrikse ◽  
...  
Keyword(s):  
High Resolution ◽  
Cognitive Decline ◽  
Ex Vivo ◽  
Brain Slices ◽  
Postmortem Brain ◽  
Vascular Pathology ◽  
Elderly Subjects ◽  
Postmortem Brain Tissue ◽  
Fluid Attenuated Inversion Recovery

Cerebrovascular disease has an important role in cognitive decline and dementia. In this context, cerebral microinfarcts are attracting increasing attention, but these lesions could thus far not be detected in vivo. The aim of this study was to try to identify possible cortical microinfarcts on high-resolution 7T in vivo magnetic resonance imaging (MRI) and to perform a histopathologic validation study on similar appearing lesions on 7T ex vivo MRI of postmortem brain tissue. The study population consisted of 22 elderly subjects, who underwent 7T MRI. The fluid attenuated inversion recovery, T2, and T1 weighted scans of these subjects were examined for possible cortical microinfarcts. In the ex vivo MRI study, 15 formalin-fixed coronal brain slices of 6 subjects with Alzheimer and vascular pathology were examined and subjected to histopathologic verification. On the in vivo scans, 15 cortical lesions could be identified that were likely to be microinfarcts in 6 subjects. In the postmortem tissue, 6 similar appearing lesions were identified of which 5 were verified as cortical microinfarcts on histopathology. This study provides strong evidence that cortical microinfarcts can be detected in vivo, which will be of great value in further studies into the role of vascular disease in cognitive decline and dementia.

scholarly journals A human antibody selective for transthyretin amyloid removes cardiac amyloid through phagocytic immune cells

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Aubin Michalon ◽  
Andreas Hagenbuch ◽  
Christian Huy ◽  
Evita Varela ◽  
Benoit Combaluzier ◽  
...  
Keyword(s):  
Immune Cells ◽  
Ex Vivo ◽  
Phase 1 ◽  
Hereditary Disease ◽  
Elderly Subjects ◽  
Human Antibody ◽  
Cardiac Amyloid ◽  
Healthy Elderly ◽  
Ongoing Phase

AbstractTransthyretin amyloid (ATTR) cardiomyopathy is a debilitating disease leading to heart failure and death. It is characterized by the deposition of extracellular ATTR fibrils in the myocardium. Reducing myocardial ATTR load is a therapeutic goal anticipated to translate into restored cardiac function and improved patient survival. For this purpose, we developed the selective anti-ATTR antibody NI301A, a recombinant human monoclonal immunoglobulin G1. NI301A was cloned following comprehensive analyses of memory B cell repertoires derived from healthy elderly subjects. NI301A binds selectively with high affinity to the disease-associated ATTR aggregates of either wild-type or variant ATTR related to sporadic or hereditary disease, respectively. It does not bind physiological transthyretin. NI301A removes ATTR deposits ex vivo from patient-derived myocardium by macrophages, as well as in vivo from mice grafted with patient-derived ATTR fibrils in a dose- and time-dependent fashion. The biological activity of ATTR removal involves antibody-mediated activation of phagocytic immune cells including macrophages. These data support the evaluation of safety and tolerability of NI301A in an ongoing phase 1 clinical trial in patients with ATTR cardiomyopathy.

scholarly journals In VivoVisualization of Heterogeneous Intratumoral Distribution of Hypoxia-Inducible Factor-1αActivity by the Fusion of High-Resolution SPECT and Morphological Imaging Tests

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Hirofumi Fujii ◽  
Masayuki Yamaguchi ◽  
Kazumasa Inoue ◽  
Yasuko Mutou ◽  
Masashi Ueda ◽  
...  
Keyword(s):  
High Resolution ◽  
Ex Vivo ◽  
Hypoxia Inducible Factor ◽  
Chimeric Protein ◽  
Small Animal ◽  
Ct Scanner ◽  
Heterogeneous Distribution ◽  
Fusion Images ◽  
Intratumoral Distribution

Purpose. We aimed to clearly visualize heterogeneous distribution of hypoxia-inducible factor 1α(HIF) activity in tumor tissuesin vivo.Methods. We synthesized of125I-IPOS, a125I labeled chimeric protein probe, that would visualize HIF activity. The biodistribution of125I-IPOS in FM3A tumor-bearing mice was evaluated. Then, the intratumoral localization of this probe was observed by autoradiography, and it was compared with histopathological findings. The distribution of125I-IPOS in tumors was imaged by a small animal SPECT/CT scanner. The obtainedin vivoSPECT-CT fusion images were compared withex vivoimages of excised tumors. Fusion imaging with MRI was also examined.Results.125I-IPOS well accumulated in FM3A tumors. The intratumoral distribution of125I-IPOS by autoradiography was quite heterogeneous, and it partially overlapped with that of pimonidazole. High-resolution SPECT-CT fusion images successfully demonstrated the heterogeneity of125I-IPOS distribution inside tumors. SPECT-MRI fusion images could give more detailed information about the intratumoral distribution of125I-IPOS.Conclusion. High-resolution SPECT images successfully demonstrated heterogeneous intratumoral distribution of125I-IPOS. SPECT-CT fusion images, more favorably SPECT-MRI fusion images, would be useful to understand the features of heterogeneous intratumoral expression of HIF activityin vivo.

scholarly journals Understanding the Effects of General Anesthetics on Cortical Network Activity Using Ex Vivo Preparations

2019 ◽  
Vol 130 (6) ◽  
pp. 1049-1063 ◽  
Author(s):  
Logan J. Voss ◽  
Paul S. García ◽  
Harald Hentschke ◽  
Matthew I. Banks
Keyword(s):  
Molecular Mechanisms ◽  
Ex Vivo ◽  
Brain Slices ◽  
Brain Regions ◽  
Cortical Network ◽  
Network Activity ◽  
Common Mechanism ◽  
General Anesthetics ◽  
Neural Basis

Abstract General anesthetics have been used to ablate consciousness during surgery for more than 150 yr. Despite significant advances in our understanding of their molecular-level pharmacologic effects, comparatively little is known about how anesthetics alter brain dynamics to cause unconsciousness. Consequently, while anesthesia practice is now routine and safe, there are many vagaries that remain unexplained. In this paper, the authors review the evidence that cortical network activity is particularly sensitive to general anesthetics, and suggest that disruption to communication in, and/or among, cortical brain regions is a common mechanism of anesthesia that ultimately produces loss of consciousness. The authors review data from acute brain slices and organotypic cultures showing that anesthetics with differing molecular mechanisms of action share in common the ability to impair neurophysiologic communication. While many questions remain, together, ex vivo and in vivo investigations suggest that a unified understanding of both clinical anesthesia and the neural basis of consciousness is attainable.

scholarly journals Inhibition of Autism-Related Crm1 Disrupts Mitosis and Induces Apoptosis of the Cortical Neural Progenitors

2020 ◽  
Vol 30 (7) ◽  
pp. 3960-3976
Author(s):  
Xue Li ◽  
Yue Feng ◽  
Meifang Yan ◽  
Xiaomeng Tu ◽  
Bin Xie ◽  
...  
Keyword(s):  
Chromosome Segregation ◽  
Spindle Assembly Checkpoint ◽  
De Novo ◽  
Ex Vivo ◽  
Brain Slices ◽  
Neural Progenitors ◽  
Embryonic Brain ◽  
Mitotic Slippage ◽  
Developing Mouse Brain

Abstract De novo microdeletion of chromosome 2p15–16.1 presents clinically recognizable phenotypes that include mental retardation, autism, and microcephaly. Chromosomal maintenance 1 (CRM1) is a gene commonly missing in patients with 2p15–16.1 microdeletion and one of two genes found in the smallest deletion case. In this study, we investigate the role and mechanism of Crm1 in the developing mouse brain by inhibiting the protein or knocking down the gene in vivo. Inhibition of Crm1 reduces the proliferation and increases p53-dependent apoptosis of the cortical neural progenitors, thereby impeding the growth of embryonic cerebral cortex. Live imaging of mitosis in ex vivo embryonic brain slices reveals that inhibition of CRM1 arrests the cortical progenitors at metaphase. The arrested cells eventually slip into a pseudo-G1 phase without chromosome segregation. The mitotic slippage cells are marked by persistent expression of the spindle assembly checkpoint (SAC), repressing of which rescues the cells from apoptosis. Our study reveals that activating the SAC and inducing the mitotic slippage may lead to apoptosis of the cortical neural progenitors. The resulting cell death may well contribute to microcephaly associated with microdeletion of chromosome 2p15–16.1 involving CRM1.

Activation of a Classic Hunger Circuit Slows Luteinizing Hormone Pulsatility

2019 ◽  
Vol 110 (7-8) ◽  
pp. 671-687 ◽  
Author(s):  
Eulalia A. Coutinho ◽  
Melanie Prescott ◽  
Sabine Hessler ◽  
Christopher J. Marshall ◽  
Allan E. Herbison ◽  
...  
Keyword(s):  
Luteinizing Hormone ◽  
Ex Vivo ◽  
Polycystic Ovary ◽  
Brain Slices ◽  
Pulse Frequency ◽  
Pulse Generation ◽  
Electrophysiological Studies ◽  
The Impact ◽  
Lh Secretion

Introduction: The central regulation of fertility is carefully coordinated with energy homeostasis, and infertility is frequently the outcome of energy imbalance. Neurons in the hypothalamus expressing neuropeptide Y and agouti-related peptide (NPY/AgRP neurons) are strongly implicated in linking metabolic cues with fertility regulation. Objective: We aimed here to determine the impact of selectively activating NPY/AgRP neurons, critical regulators of metabolism, on the activity of luteinizing hormone (LH) pulse generation. Methods: We employed a suite of in vivo optogenetic and chemogenetic approaches with serial measurements of LH to determine the impact of selectively activating NPY/AgRP neurons on dynamic LH secretion. In addition, electrophysiological studies in ex vivo brain slices were employed to ascertain the functional impact of activating NPY/AgRP neurons on gonadotropin-releasing hormone (GnRH) neurons. Results: Selective activation of NPY/AgRP neurons significantly decreased post-castration LH secretion. This was observed in males and females, as well as in prenatally androgenized females that recapitulate the persistently elevated LH pulse frequency characteristic of polycystic ovary syndrome (PCOS). Reduced LH pulse frequency was also observed when optogenetic stimulation was restricted to NPY/AgRP fiber projections surrounding GnRH neuron cell bodies in the rostral preoptic area. However, electrophysiological studies in ex vivo brain slices indicated these effects were likely to be indirect. Conclusions: These data demonstrate the ability of NPY/AgRP neuronal signaling to modulate and, specifically, reduce GnRH/LH pulse generation. The findings suggest a mechanism by which increased activity of this hunger circuit, in response to negative energy balance, mediates impaired fertility in otherwise reproductively fit states, and highlight a potential mechanism to slow LH pulsatility in female infertility disorders, such as PCOS, that are associated with hyperactive LH secretion.

scholarly journals Smartphone microendoscopy for high resolution fluorescence imaging

2016 ◽  
Vol 09 (05) ◽  
pp. 1650046 ◽  
Author(s):  
Xiangqian Hong ◽  
Vivek K. Nagarajan ◽  
Dale H. Mugler ◽  
Bing Yu
Keyword(s):  
High Resolution ◽  
Rural Areas ◽  
Ex Vivo ◽  
Cost Effective ◽  
Internal Organs ◽  
Middle Income ◽  
Middle Income Countries ◽  
The Past

High resolution optical endoscopes are increasingly used in diagnosis of various medical conditions of internal organs, such as the cervix and gastrointestinal (GI) tracts, but they are too expensive for use in resource-poor settings. On the other hand, smartphones with high resolution cameras and Internet access have become more affordable, enabling them to diffuse into most rural areas and developing countries in the past decade. In this paper, we describe a smartphone microendoscope that can take fluorescence images with a spatial resolution of 3.1 [Formula: see text]m. Images collected from ex vivo, in vitro and in vivo samples using the device are also presented. The compact and cost-effective smartphone microendoscope may be envisaged as a powerful tool for detecting pre-cancerous lesions of internal organs in low and middle-income countries (LMICs).

scholarly journals A computational atlas of the hippocampal formation using ex vivo , ultra-high resolution MRI: Application to adaptive segmentation of in vivo MRI

NeuroImage ◽  
2015 ◽  
Vol 115 ◽  
pp. 117-137 ◽  
Author(s):  
Juan Eugenio Iglesias ◽  
Jean C. Augustinack ◽  
Khoa Nguyen ◽  
Christopher M. Player ◽  
Allison Player ◽  
...  
Keyword(s):  
High Resolution ◽  
Hippocampal Formation ◽  
Ex Vivo ◽  
Adaptive Segmentation ◽  
High Resolution Mri
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