scholarly journals A multimodal computational pipeline for 3D histology of the human brain

2020 ◽  
Author(s):  
Matteo Mancini ◽  
Adrià Casamitjana ◽  
Loic Peter ◽  
Eleanor Robinson ◽  
Shauna Crampsie ◽  
...  
Keyword(s):  
Human Brain ◽  
Ex Vivo ◽  
Imaging Modality ◽  
3D Structure ◽  
Microscopic Level ◽  
Level Of Detail ◽  
Computational Pipeline ◽  
Volumetric Mri ◽  
Mri Scan

AbstractEx vivo imaging enables analysis of the human brain at a level of detail that is not possible in vivo with MRI. In particular, histology can be used to study brain tissue at the microscopic level, using a wide array of different stains that highlight different microanatomical features. Complementing MRI with histology has important applications in ex vivo atlas building and in modeling the link between microstructure and macroscopic MR signal. However, histology requires sectioning tissue, hence distorting its 3D structure, particularly in larger human samples. Here, we present an open-source computational pipeline to produce 3D consistent histology reconstructions of the human brain. The pipeline relies on a volumetric MRI scan that serves as undistorted reference, and on an intermediate imaging modality (blockface photography) that bridges the gap between MRI and histology. We present results on 3D histology reconstruction of a whole human hemisphere.

A Three-Component-System Hypothesis of Psychosis

1989 ◽  
Vol 155 (S5) ◽  
pp. 37-39 ◽  
Author(s):  
Hinderk M. Emrich
Keyword(s):  
Human Brain ◽  
Causative Factor ◽  
Microscopic Level ◽  
Point Of View ◽  
Component System ◽  
Pathogenetic Factor ◽  
Pet Scans ◽  
The Brain ◽  
Different Levels

Hypotheses as to the pathogenesis of schizophrenia can be discussed at different levels of a possible manifestation of the causative factor: the macroscopic-morphological, the microscopic-morphological, and the molecular. Some abnormalities have been observed on all of them: e.g. increased ventricular-brain ratios in CT, hypofrontality in SPECT and in glucographic PET-scans, and other macromorphological abnormalities (for reviews cf. Bogerts 1984; Mundt, 1986; Bogerts et al, 1987), gliosis on a microscopic level (Stevens, 1982), and an increased dopamine-binding in in vivo receptor studies (PET as well as in post-mortem studies; Cazzullo, 1988). However, the diversity and variability of these findings point to the view that rather than there being a single distinct pathogenetic factor responsible for the pathogenesis of schizophrenic psychoses, a constitutional disposition exists, which can be described as a functional dysequilibrium within the human brain. From this point of view, schizophrenia would not appear as an inherited disorder of metabolism, but as a weakness of a neurobiological ‘system’, i.e. as an interactional disorder of a complex of networks, in which the interaction between different substructures is labile in such a way that under special conditions (e.g. ‘stress’), a decompensation (functional breakdown) results. In this sense, ‘vulnerability’ to schizophrenia may be interpreted as a consequence of a constitutional deficiency of the brain which results in an inability to stabilise, under specially challenging conditions, the interaction between different substructures of the human brain. Before this ‘functional dysequilibrium-hypothesis’ (which is a special form of a constitutional structural deficiency-hypothesis) is discussed, and before the question is raised as to which are the relevant dysequilibrated components, some indication will be given as to why such an hypothesis appears plausible.

scholarly journals Multi-Aspect Optoacoustic Imaging of Breast Tumors under Chemotherapy with Exogenous and Endogenous Contrasts: Focus on Apoptosis and Hypoxia

Biomedicines ◽  
2021 ◽  
Vol 9 (11) ◽  
pp. 1696
Author(s):  
Angelos Karlas ◽  
Antonio Nunes ◽  
Wouter Driessen ◽  
Evangelos Liapis ◽  
Josefine Reber
Keyword(s):  
Breast Cancer ◽  
Ex Vivo ◽  
Imaging Modality ◽  
Therapy Response ◽  
Breast Tumors ◽  
Chemotherapeutic Agents ◽  
Tumor Type ◽  
Optoacoustic Imaging ◽  
Deoxygenated Hemoglobin

Breast cancer is a complex tumor type involving many biological processes. Most chemotherapeutic agents exert their antitumoral effects by rapid induction of apoptosis. Another main feature of breast cancer is hypoxia, which may drive malignant progression and confer resistance to various forms of therapy. Thus, multi-aspect imaging of both tumor apoptosis and oxygenation in vivo would be of enormous value for the effective evaluation of therapy response. Herein, we demonstrate the capability of a hybrid imaging modality known as multispectral optoacoustic tomography (MSOT) to provide high-resolution, simultaneous imaging of tumor apoptosis and oxygenation, based on both the exogenous contrast of an apoptosis-targeting dye and the endogenous contrast of hemoglobin. MSOT imaging was applied on mice bearing orthotopic 4T1 breast tumors before and following treatment with doxorubicin. Apoptosis was monitored over time by imaging the distribution of xPLORE-APOFL750©, a highly sensitive poly-caspase binding apoptotic probe, within the tumors. Oxygenation was monitored by tracking the distribution of oxy- and deoxygenated hemoglobin within the same tumor areas. Doxorubicin treatment induced an increase in apoptosis-depending optoacoustic signal of xPLORE-APOFL750© at 24 h after treatment. Furthermore, our results showed spatial correspondence between xPLORE-APO750© and deoxygenated hemoglobin. In vivo apoptotic status of the tumor tissue was independently verified by ex vivo fluorescence analysis. Overall, our results provide a rationale for the use of MSOT as an effective tool for simultaneously investigating various aspects of tumor pathophysiology and potential effects of therapeutic regimes based on both endogenous and exogenous molecular contrasts.

Abstract 1143: Imaging of Vasa Vasorum in Atherosclerotic Plaque with 99m Tc-labeled single chain-VEGF

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Satoru Ohshima ◽  
Shinichiro Fujimoto ◽  
Sotirios Tsimikas ◽  
Frank D Kolodgie ◽  
Renu Virmani ◽  
...  
Keyword(s):  
Atherosclerotic Plaque ◽  
Ex Vivo ◽  
Imaging Modality ◽  
Atherosclerotic Lesion ◽  
Vasa Vasorum ◽  
Intraplaque Hemorrhage ◽  
Control Group ◽  
High Cholesterol Diet ◽  
Single Chain

Introduction: Adventitial vasa vasorum proliferation and neointimal neovascularization are associated with intraplaque hemorrhage, expansion of necrotic core and hence plaque vulnerability. Increased expression of VEGF and its receptors accompany neoangiogenic process. We used 99m Tc -labeled single chain VEGF (TcV) for developing potentially noninvasive imaging modality in experimentally induced aortic atherosclerotic lesion. Methods : Noninva-sive radionuclide imaging was performed with TcV (6.85 ±0. 27 mCi) in 6 NZW rabbits receiving high cholesterol diet (0.2% cholesterol, 4% fat) for one year and compared with 3 control rabbits receiving normal rabbit chow. Four hours after intravenous administration of TcV, micro SPECT/microCT imaging was performed for in vivo localization of tracer activity. Aortas were then explanted, and gamma counted for determination of % injected dose per gram (%ID/g). The aortas were then submitted for histopathologic characterization. Results : The uptake in thoracic aorta was clearly visualized non-invasively by TcV in vivo imaging in 4 of 5 rabbits in hypercholesterolemic rabbits, but not in the control animals. The %ID/g of each parts of aorta in hypercholesterolemic rabbits (Arch : 0.036 ± 0.020 %, Thoracic : 0.026 ± 0.012 %, Abd : 0.019 ± 0.009 %) was about 2.5-fold higher than that in control group (Arch : 0.014 ± 0.004 %, Thoracic : 0.009 ± 0.003 %, Abd : 0.009 ± 0.003 %) (figure a ). Ex vivo images of each group are shown as figure b . Conclusions : This preliminary study suggests a potentially novel strategy for non-invasive imaging of neoangiogenesis in atherosclerotic plaque and may allow identification of unstable plaques.

scholarly journals A new method for accurate in vivo mapping of human brain connections using microstructural and anatomical information

2020 ◽  
Vol 6 (31) ◽  
pp. eaba8245 ◽  
Author(s):  
Simona Schiavi ◽  
Mario Ocampo-Pineda ◽  
Muhamed Barakovic ◽  
Laurent Petit ◽  
Maxime Descoteaux ◽  
...  
Keyword(s):  
Human Brain ◽  
Imaging Modality ◽  
Brain Anatomy ◽  
Major Step ◽  
Wide Range ◽  
Noninvasive Imaging Modality ◽  
Novel Processing ◽  
Brain Data ◽  
Anatomical Information

Diffusion magnetic resonance imaging is a noninvasive imaging modality that has been extensively used in the literature to study the neuronal architecture of the brain in a wide range of neurological conditions using tractography. However, recent studies highlighted that the anatomical accuracy of the reconstructions is inherently limited and challenged its appropriateness. Several solutions have been proposed to tackle this issue, but none of them proved effective to overcome this fundamental limitation. In this work, we present a novel processing framework to inject into the reconstruction problem basic prior knowledge about brain anatomy and its organization and evaluate its effectiveness using both simulated and real human brain data. Our results indicate that our proposed method dramatically increases the accuracy of the estimated brain networks and, thus, represents a major step forward for the study of connectivity.

scholarly journals Imaging Multiple Sclerosis Pathology at 160μm Isotropic Resolution by Human Whole-Brain Ex Vivo Magnetic Resonance Imaging at 3T

2021 ◽  
Author(s):  
Weigel Matthias ◽  
Dechent Peter ◽  
Galbusera Riccardo ◽  
Bahn Erik ◽  
Nair Govind ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Multiple Sclerosis ◽  
Magnetic Resonance ◽  
Human Brain ◽  
Ex Vivo ◽  
Molecular Layer ◽  
Cortical Lesion ◽  
Resonance Imaging ◽  
Whole Brain

AbstractPostmortem magnetic resonance imaging (MRI) of the fixed healthy and diseased human brain facilitates spatial resolutions and image quality that is not achievable with in vivo MRI scans. Though challenging - and almost exclusively performed at 7T field strength - depicting the tissue architecture of the entire brain in fine detail is invaluable since it enables the study of neuroanatomy and uncovers important pathological features in neurological disorders. The objectives of the present work were (i) to develop a 3D isotropic ultra-high-resolution imaging approach for human whole-brain ex vivo acquisitions working on a standard clinical 3T MRI system, and (ii) to explore the sensitivity and specificity of this concept for specific pathoanatomical features of multiple sclerosis. The reconstructed images demonstrate unprecedented resolution and soft tissue contrast of the diseased human brain at 3T, thus allowing visualization of sub-millimetric lesions in the different cortical layers and in the cerebellar cortex, as well as unique cortical lesion characteristics such as the presence of incomplete / complete iron rims, and patterns of iron accumulation. Further details such as the subpial molecular layer, the line of Gennari, and some intrathalamic nuclei are also well distinguishable.

scholarly journals Development of Magnetic Particle Imaging (MPI) for Cell Tracking and Detection

2020 ◽  
Author(s):  
Kierstin P Melo ◽  
Ashley V Makela ◽  
Natasha N Knier ◽  
Amanda M Hamilton ◽  
Paula J Foster
Keyword(s):  
Iron Content ◽  
Cell Tracking ◽  
Magnetic Particle ◽  
Ex Vivo ◽  
Imaging Modality ◽  
Superparamagnetic Iron Oxide ◽  
Cell Injection ◽  
Magnetic Particle Imaging ◽  
Particle Imaging

AbstractIntroductionMagnetic particle imaging (MPI) is a new imaging modality that sensitively and specifically detects superparamagnetic iron oxide nanoparticles (SPIONs) within a sample. SPION-based MRI cell tracking has very high sensitivity, but low specificity and quantification of iron labeled cells is difficult. MPI cell tracking could overcome these challenges.MethodsMDM-AB-231BR cells labeled with MPIO, mice were intracardially injected with either 2.5 × 105 or 5.0 × 105 cells. MRI was performed in vivo the same day at 3T using a bSSFP sequence. After mice were imaged ex vivo with MPI. In a second experiment Mice received an intracardiac injection of either 2.5 × 10 5 or 5 × 10 4 MPIO-labeled 231BR cells. In a third experiment, mice were injected with 5 × 10 4 4T1BR cells, labelled with either MPIO or the SPION Vivotrax. MRI and MPI was performed in vivo.ResultsSignal from MPI and signal voids from MRI both showed more iron content in mice receiving an injection of 5.0 × 105 cells than the 2.5 × 105 injection. In the second experiment, Day 0 MRI showed signal voids and MPI signal was detected in all mouse brains. The MPI signal and iron content measured in the brains of mice that were injected with 2.5 × 10 5 cells were approximately four times greater than in brains injected with 5 × 10 4 cells. In the third experiment, in vivo MRI was able to detect signal voids in the brains of mice injected with Vivotrax and MPIO, although voids were fainter in Vivotrax labeled cells. In vivo MPI signal was only detectable in mice injected with MPIO-labeled cells.ConclusionThis is the first example of the use of MPIO for cell tracking with MPI. With an intracardiac cell injection, approximately 15% of the injected cells are expected to arrest in the brain vasculature. For our lowest cell injection of 5.0 × 104 cells this is ∼10000 cells.

scholarly journals Human cerebrospinal fluid induces neuronal excitability changes in resected human neocortical and hippocampal brain slices

2019 ◽  
Author(s):  
Jenny Wickham ◽  
Andrea Corna ◽  
Niklas Schwarz ◽  
Betül Uysal ◽  
Nikolas Layer ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Human Brain ◽  
Brain Tissue ◽  
Ex Vivo ◽  
Brain Slices ◽  
Electrophysiological Recording ◽  
Recording Medium ◽  
Human Brain Tissue ◽  
Human Cerebrospinal Fluid

AbstractHuman cerebrospinal fluid (hCSF) have proven advantageous over conventional medium when culturing both rodent and human brain tissue. Increased excitability and synchronicity, similar to the active state exclusively recorded in vivo, reported in rodent slice and cell-cultures with hCSF as recording medium, indicates properties of the hCSF not matched by the artificial cerebrospinal fluid (aCSF) commonly used for electrophysiological recording. To evaluate the possible importance of using hCSF as electrophysiological recording medium of human brain tissue, we compared the general excitability in ex vivo human brain tissue slice cultures during perfusion with hCSF and aCSF. For measuring the general activity from a majority of neurons within neocortical and hippocampal human ex vivo slices we used a microelectrode array (MEA) recording technique with 252 electrodes covering an area of 3.2 x 3.2 mm2 and a second CMOS-based MEA with 4225 electrodes on a 2 x 2 mm2 area for detailed mapping of action potential waveforms. We found that hCSF increase the number of active neurons and the firing rate of the neurons in the slices as well as increasing the numbers of bursts while leaving the duration of the bursts unchanged. Interestingly, not only an increase in the overall activity in the slices was observed, but a reconfiguration of the network functionality could be detected with specific activation and inactivation of subpopulations of neuronal ensembles. In conclusion, hCSF is an important component to consider for future human tissue studies, especially for experiments designed to mimic the in vivo situation.

scholarly journals Detection of human brain cancer infiltration ex vivo and in vivo using quantitative optical coherence tomography

2015 ◽  
Vol 7 (292) ◽  
pp. 292ra100-292ra100 ◽  
Author(s):  
Carmen Kut ◽  
Kaisorn L. Chaichana ◽  
Jiefeng Xi ◽  
Shaan M. Raza ◽  
Xiaobu Ye ◽  
...  
Keyword(s):  
Optical Coherence Tomography ◽  
Human Brain ◽  
Brain Cancer ◽  
Ex Vivo ◽  
Optical Coherence

Ex vivo and in vivo imaging of human brain tissue with different OCT systems

2019 ◽  
Author(s):  
Paul Strenge ◽  
Birgit Lange ◽  
Christin Grill ◽  
Wolfgang Draxinger ◽  
Veit Danicke ◽  
...  
Keyword(s):  
Human Brain ◽  
Brain Tissue ◽  
In Vivo Imaging ◽  
Ex Vivo ◽  
Human Brain Tissue

scholarly journals Superficial white matter fiber systems impede detection of long-range cortical connections in diffusion MR tractography

2015 ◽  
Vol 112 (21) ◽  
pp. E2820-E2828 ◽  
Author(s):  
Colin Reveley ◽  
Anil K. Seth ◽  
Carlo Pierpaoli ◽  
Afonso C. Silva ◽  
David Yu ◽  
...  
Keyword(s):  
White Matter ◽  
High Resolution ◽  
Human Brain ◽  
Long Range ◽  
Ex Vivo ◽  
Cortical Surface ◽  
Tracer Injection ◽  
Axonal Projections ◽  
Probabilistic Tracking

In vivo tractography based on diffusion magnetic resonance imaging (dMRI) has opened new doors to study structure–function relationships in the human brain. Initially developed to map the trajectory of major white matter tracts, dMRI is used increasingly to infer long-range anatomical connections of the cortex. Because axonal projections originate and terminate in the gray matter but travel mainly through the deep white matter, the success of tractography hinges on the capacity to follow fibers across this transition. Here we demonstrate that the complex arrangement of white matter fibers residing just under the cortical sheet poses severe challenges for long-range tractography over roughly half of the brain. We investigate this issue by comparing dMRI from very-high-resolution ex vivo macaque brain specimens with histological analysis of the same tissue. Using probabilistic tracking from pure gray and white matter seeds, we found that ∼50% of the cortical surface was effectively inaccessible for long-range diffusion tracking because of dense white matter zones just beneath the infragranular layers of the cortex. Analysis of the corresponding myelin-stained sections revealed that these zones colocalized with dense and uniform sheets of axons running mostly parallel to the cortical surface, most often in sulcal regions but also in many gyral crowns. Tracer injection into the sulcal cortex demonstrated that at least some axonal fibers pass directly through these fiber systems. Current and future high-resolution dMRI studies of the human brain will need to develop methods to overcome the challenges posed by superficial white matter systems to determine long-range anatomical connections accurately.

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