scholarly journals Multimodal Magnetic Resonance Histology and Light Sheet Imaging for Quantitative Neurogenetics of the Mouse

2021 ◽  
Author(s):  
G. Allan Johnson ◽  
Gary Cofer ◽  
James Cook ◽  
James Gee ◽  
Adam Hall ◽  
...  
Keyword(s):  
Magnetic Resonance ◽  
Spatial Resolution ◽  
Mouse Brain ◽  
Angular Resolution ◽  
Imaging Techniques ◽  
Brain Connectivity ◽  
Light Sheet ◽  
Whole Brain ◽  
Light Sheet Microscopy

Paul Lauterbur closed his seminal paper on MRI with the statement that "zeugmatographic (imaging) techniques should find many useful applications in studies of the internal structures, states and composition of microscopic objects" {Lauterbur, 1973 #967}. Magnetic resonance microscopy was subsequently demonstrated in 1986 by three groups{Aguayo, 1986 #968}{Eccles, 1986 #969}{Johnson, 1986 #970}. The application of MRI to the study of tissue structure, i.e. magnetic resonance histology (MRH) was suggested in 1993 {Johnson, 1993 #957}. MRH, while based on the same physical principals as MRI is something fundamentally different than the clinical exams which are typically limited to voxel dimensions of ~ 1 mm3. Preclinical imaging systems can acquire images with voxels ~ 1000 times smaller. The MR histology images presented here have been acquired at yet another factor of 1000 increase in spatial resolution. Figure S1 in the supplement shows a comparison of a state-of-the-art fractional anisotropy images of a C57 mouse brain in vivo @ 150 um resolution (voxel volume of 3.3 x10-3 mm3) with the atlas we have generated for this work at 15 um spatial resolution (voxel volume of 3.3 x 10-6 mm3). In previous work, we have demonstrated the utility of MR histology in neurogenetics at spatial/angular resolution of 45 um /46 angles {Wang N, 2020 #972}. At this spatial/angular resolution it is possible to map whole brain connectivity with high correspondence to retroviral tracers {Calabrese, 2015 #895}. But the MRH derived connectomes can be derived in less than a day where the retroviral tracer studies require months/years {Oh, 2014 #971}. The resolution index (angular samples/voxel volume) for this previous work was >500,000 {Johnson, 2018 #894}. Figure S2 shows a comparison between that previous work and the new atlas presented in this paper with a resolution index of 32 million. Light sheet microscopy (LSM) has undergone similar rapid evolution over the last 20 years. The invention of tissue clearing, advances in immuno histochemistry and development of selective plane illumination microscopy (SPIM) now make it possible to acquire whole mouse brain images at submicron spatial resolution with a vast array of cell specific markers{Ueda, 2020 #974}{Park, 2018 #953}{Murray, 2015 #952}{Gao, 2014 #973}. And these advantages can be realized in scan times of < 6hrs. The major limitation from these studies is the distortion in the tissue from dissection from the cranium, swelling from clearing and staining, and tissue damage from handling. We report here the merger of these two methods: 1. MRH with the brain in the skull to provide accurate geometry, cytoarchitectural measures using scalar imaging metrics and whole brain connectivity at 15 um isotropic spatial resolution with super resolution track density images @ 5 um isotropic resolution; 2. whole brain multichannel LSM @ 1.8x1.8x4.0 um; 3. a big image data infrastructure that enables label mapping from the atlas to the MR image, geometric correction to the light sheet data, label mapping to the light sheet volumes and quantitative extraction of regional cell density. These methods make it possible to generate a comprehensive collection of image derived phenotypes (IDP) of cells and circuits covering the whole mouse brain with throughput that can be scaled for quantitative neurogenetics.

scholarly journals Dual-slit confocal light sheet microscopy for in vivo whole-brain imaging of zebrafish

2015 ◽  
Vol 6 (5) ◽  
pp. 1797 ◽  
Author(s):  
Zhe Yang ◽  
Li Mei ◽  
Fei Xia ◽  
Qingming Luo ◽  
Ling Fu ◽  
...  
Keyword(s):  
Brain Imaging ◽  
Light Sheet ◽  
Whole Brain ◽  
Light Sheet Microscopy

Trends in Nanotechnology for in vivo Cancer Diagnosis: Products and Patents

2020 ◽  
Vol 26 (18) ◽  
pp. 2167-2181
Author(s):  
Tatielle do Nascimento ◽  
Melanie Tavares ◽  
Mariana S.S.B. Monteiro ◽  
Ralph Santos-Oliveira ◽  
Adriane R. Todeschini ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Quantum Dots ◽  
Magnetic Resonance ◽  
Metal Nanoparticles ◽  
Cancer Diagnosis ◽  
Imaging Techniques ◽  
Tumor Detection ◽  
Abnormal Growth ◽  
Pharmaceutical Nanotechnology

Background: Cancer is a set of diseases formed by abnormal growth of cells leading to the formation of the tumor. The diagnosis can be made through symptoms’ evaluation or imaging tests, however, the techniques are limited and the tumor detection may be late. Thus, pharmaceutical nanotechnology has emerged to optimize the cancer diagnosis through nanostructured contrast agent’s development. Objective: This review aims to identify commercialized nanomedicines and patents for cancer diagnosis. Methods: The databases used for scientific articles research were Pubmed, Science Direct, Scielo and Lilacs. Research on companies’ websites and articles for the recognition of commercial nanomedicines was performed. The Derwent tool was applied for patent research. Results: This article aimed to research on nanosystems based on nanoparticles, dendrimers, liposomes, composites and quantum dots, associated to imaging techniques. Commercialized products based on metal and composite nanoparticles, associated with magnetic resonance and computed tomography, have been observed. The research conducted through Derwent tool displayed a small number of patents using nanotechnology for cancer diagnosis. Among these patents, the most significant number was related to the use of systems based on metal nanoparticles, composites and quantum dots. Conclusion: Although few systems are found in the market and patented, nanotechnology appears as a promising field for the development of new nanosystems in order to optimize and accelerate the cancer diagnosis.

scholarly journals Hyperpolarized 13C-glucose magnetic resonance highlights reduced aerobic glycolysis in vivo in infiltrative glioblastoma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mor Mishkovsky ◽  
Olga Gusyatiner ◽  
Bernard Lanz ◽  
Cristina Cudalbu ◽  
Irene Vassallo ◽  
...  
Keyword(s):  
Magnetic Resonance ◽  
Tumor Recurrence ◽  
Aerobic Glycolysis ◽  
Imaging Techniques ◽  
Tumor Type ◽  
Hyperpolarized 13C ◽  
Metabolic Heterogeneity ◽  
Metabolic Information ◽  
Opposite Response

AbstractGlioblastoma (GBM) is the most aggressive brain tumor type in adults. GBM is heterogeneous, with a compact core lesion surrounded by an invasive tumor front. This front is highly relevant for tumor recurrence but is generally non-detectable using standard imaging techniques. Recent studies demonstrated distinct metabolic profiles of the invasive phenotype in GBM. Magnetic resonance (MR) of hyperpolarized 13C-labeled probes is a rapidly advancing field that provides real-time metabolic information. Here, we applied hyperpolarized 13C-glucose MR to mouse GBM models. Compared to controls, the amount of lactate produced from hyperpolarized glucose was higher in the compact GBM model, consistent with the accepted “Warburg effect”. However, the opposite response was observed in models reflecting the invasive zone, with less lactate produced than in controls, implying a reduction in aerobic glycolysis. These striking differences could be used to map the metabolic heterogeneity in GBM and to visualize the infiltrative front of GBM.

scholarly journals Tracking Transplanted Stem Cells Using Magnetic Resonance Imaging and the Nanoparticle Labeling Method in Urology

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Jae Heon Kim ◽  
Hong J. Lee ◽  
Yun Seob Song
Keyword(s):  
Magnetic Resonance Imaging ◽  
Stem Cells ◽  
Molecular Imaging ◽  
Magnetic Resonance ◽  
Imaging Modality ◽  
Imaging Techniques ◽  
Image Resolution ◽  
Imaging Method ◽  
Resonance Imaging

A reliablein vivoimaging method to localize transplanted cells and monitor their viability would enable a systematic investigation of cell therapy. Most stem cell transplantation studies have used immunohistological staining, which does not provide information about the migration of transplanted cellsin vivoin the same host. Molecular imaging visualizes targeted cells in a living host, which enables determining the biological processes occurring in transplanted stem cells. Molecular imaging with labeled nanoparticles provides the opportunity to monitor transplanted cells noninvasively without sacrifice and to repeatedly evaluate them. Among several molecular imaging techniques, magnetic resonance imaging (MRI) provides high resolution and sensitivity of transplanted cells. MRI is a powerful noninvasive imaging modality with excellent image resolution for studying cellular dynamics. Several types of nanoparticles including superparamagnetic iron oxide nanoparticles and magnetic nanoparticles have been used to magnetically label stem cells and monitor viability by MRI in the urologic field. This review focuses on the current role and limitations of MRI with labeled nanoparticles for tracking transplanted stem cells in urology.

Magnetic Resonance Elastography for the Measurement of Annulus Fibrosus Material Properties

2011 ◽  
Author(s):  
Daniel H. Cortes ◽  
Lachlan J. Smith ◽  
Sung M. Moon ◽  
Jeremy F. Magland ◽  
Alexander C. Wright ◽  
...  
Keyword(s):  
Mechanical Properties ◽  
Magnetic Resonance ◽  
Shear Modulus ◽  
Disc Degeneration ◽  
Annulus Fibrosus ◽  
Pulse Sequence ◽  
Imaging Techniques ◽  
Mechanical Vibration ◽  
Magnetic Resonance Elastography

Intervertebral disc degeneration is characterized by a progressive cascade of structural, biochemical and biomechanical changes affecting the annulus fibrosus (AF), nucleus pulposus (NP) and end plates (EP). These changes are considered to contribute to the onset of back pain. It has been shown that mechanical properties of the AF and NP change significantly with degeneration [1,2]. Therefore, mechanical properties have the potential to serve as a biomarker for diagnosis of disc degeneration. Currently, disc degeneration is diagnosed based on the detection of structural and compositional changes using MRI, X-ray, discography and other imaging techniques. These methods, however, do not measure directly the mechanical properties of the extracellular matrix of the disc. Magnetic Resonance Elastography (MRE) is a technique that has been used to measure in vivo mechanical properties of soft tissue by applying a mechanical vibration and measuring displacements with a motion-sensitized MRI pulse sequence [3]. The mechanical properties (e.g., the shear modulus) are calculated from the displacement field using an inverse method. Since the applied displacements are in the order of few microns, fibers may not be stretched enough to remove crimping. Therefore, it is unknown if the anisotropy of the AF due to the contribution of the fibers is detectable using MRE. The objective of this study is twofold: to measure shear properties of AF in different orientations to determine the degree of AF anisotropy observable by MRE, and to identify the contribution of different AF constituents to the measured shear modulus by applying different biochemical treatments.

scholarly journals Spatiotemporal co-dependency between macrophages and exhausted CD8+ T cells in cancer

2021 ◽  
Author(s):  
Kelly Kersten ◽  
Kenneth H Hu ◽  
Alexis J Combes ◽  
Bushra Samad ◽  
Tory Harwin ◽  
...  
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Light Sheet ◽  
Light Sheet Microscopy ◽  
Spatially Resolved ◽  
Hypoxic Conditions ◽  
Synaptic Interactions ◽  
Positive Feedback Circuit ◽  
Major Impediment

T cell exhaustion is a major impediment to anti-tumor immunity. However, it remains elusive how other immune cells in the tumor microenvironment (TME) contribute to this dysfunctional state. Here we show that the biology of tumor-associated macrophages (TAM) and exhausted T cells (Tex) in the TME is extensively linked. We demonstrate that in vivo depletion of TAM reduces exhaustion programs in tumor-infiltrating CD8+ T cells and reinvigorates their effector potential. Reciprocally, transcriptional and epigenetic profiling reveals that Tex express factors that actively recruit monocytes to the TME and shape their differentiation. Using lattice light sheet microscopy, we show that TAM and CD8+ T cells engage in unique long-lasting antigen-specific synaptic interactions that fail to activate T cells, but prime them for exhaustion, which is then accelerated in hypoxic conditions. Spatially resolved sequencing supports a spatiotemporal self-enforcing positive feedback circuit that is aligned to protect rather than destroy a tumor.

scholarly journals In vivo imaging techniques: a new era for histochemical analysis

2016 ◽  
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.

Multiphoton Light-sheet Microscopy at Optimal Pulse Frequency for Fast In Vivo Imaging

2020 ◽  
Author(s):  
Vincent Maioli ◽  
Antoine Boniface ◽  
Pierre Mahou ◽  
Júlia Ferrer Ortas ◽  
Lamiae Abdeladim ◽  
...  
Keyword(s):  
In Vivo Imaging ◽  
Light Sheet ◽  
Pulse Frequency ◽  
Light Sheet Microscopy
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