Fluorescence microscopy tensor imaging representations for large-scale dataset analysis

Understanding complex biological systems requires the system-wide characterization of cellular and molecular features. Recent advances in optical imaging technologies and chemical tissue clearing have facilitated the acquisition of whole-organ imaging datasets, but automated tools for their quantitative analysis and visualization are still lacking. We have here developed a visualization technique capable of providing whole-organ tensor imaging representations of local regional descriptors based on fluorescence data acquisition. This method enables rapid, multiscale, analysis and virtualization of large-volume, high-resolution complex biological data while generating 3D tractographic representations. Using the murine heart as a model, our method allowed us to analyze and interrogate the cardiac microvasculature and the tissue resident macrophage distribution and better infer and delineate the underlying structural network in unprecedented detail

Regional variations in ex-vivo diffusion tensor anisotropy are associated with cardiomyocyte remodeling in rats after left ventricular pressure overload

Background Pressure overload left ventricular (LV) hypertrophy is characterized by increased cardiomyocyte width and ventricle wall thickness, however the regional variation of this remodeling is unclear. Cardiovascular magnetic resonance (CMR) diffusion tensor imaging (DTI) may provide a non-invasive, comprehensive, and geometrically accurate method to detect regional differences in structural remodeling in hypertrophy. We hypothesized that DTI parameters, such as fractional and planar anisotropy, would reflect myocyte remodeling due to pressure overload in a regionally-dependent manner. Methods We investigated the regional distributions of myocyte remodeling in rats with or without transverse aortic constriction (TAC) via direct measurement of myocyte dimensions with confocal imaging of thick tissue sections, and correlated myocyte cross-sectional area and other geometric features with parameters of diffusivity from ex-vivo DTI in the same regions of the same hearts. Results We observed regional differences in several parameters from DTI between TAC hearts and SHAM controls. Consistent with previous studies, helix angles from DTI correlated strongly with those measured directly from histological sections (p < 0.001, R2 = 0.71). There was a transmural gradient in myocyte cross-sectional area in SHAM hearts that was diminished in the TAC group. We also found several regions of significantly altered DTI parameters in TAC LV compared to SHAM, especially in myocyte sheet angle dispersion and planar anisotropy. Among others, these parameters correlated significantly with directly measured myocyte aspect ratios. Conclusions These results show that structural remodeling in pressure overload LV hypertrophy is regionally heterogeneous, especially transmurally, with a greater degree of remodeling in the sub-endocardium compared to the sub-epicardium. Additionally, several parameters derived from DTI correlated significantly with measurements of myocyte geometry from direct measurement in histological sections. We suggest that DTI may provide a non-invasive, comprehensive method to detect regional structural myocyte LV remodeling during disease

3D Fiber Orientation in Atherosclerotic Carotid Plaques

Atherosclerotic plaque rupture is the primary trigger of fatal cardiovascular events. Fibrillar collagen in atherosclerotic plaques and their directionality are anticipated to play a crucial role in plaque rupture. This study aimed assessing 3D fiber orientations and architecture in atherosclerotic plaques for the first time.Seven carotid plaques were imaged ex-vivo with a state-of-the-art Diffusion Tensor Imaging (DTI) technique, using a high magnetic field (9.4. Tesla) MRI scanner. A 3D spin-echo sequence with uni-polar diffusion sensitizing pulsed field gradients was utilized for DTI and fiber directions were assessed from diffusion tensor measurements. The distribution of the 3D fiber orientations in atherosclerotic plaques were quantified and the principal fiber orientations (circumferential, longitudinal or radial) were determined.Overall, 52% of the fiber orientations in the carotid plaque specimens were closest to the circumferential direction, 34% to the longitudinal direction, and 14% to the radial direction. Statistically no significant difference was measured in the amount of the fiber orientations between the concentric and eccentric plaque sites. However, concentric plaque sites showed a distinct structural organization, where the principally longitudinally oriented fibers were closer to the luminal side and the principally circumferentially oriented fibers were located more abluminally. The acquired unique information on 3D plaque fiber direction will help understanding pathobiological mechanisms of atherosclerotic plaque progression and pave the road to more realistic biomechanical plaque modeling for rupture assessment

Mixed methodology in human brain research: integrating MRI and histology

Postmortem magnetic resonance imaging (MRI) can provide a bridge between histological observations and the in vivo anatomy of the human brain. Approaches aimed at the co-registration of data derived from the two techniques are gaining interest. Optimal integration of the two research fields requires detailed knowledge of the tissue property requirements for individual research techniques, as well as a detailed understanding of the consequences of tissue fixation steps on the imaging quality outcomes for both MRI and histology. Here, we provide an overview of existing studies that bridge between state-of-the-art imaging modalities, and discuss the background knowledge incorporated into the design, execution and interpretation of postmortem studies. A subset of the discussed challenges transfer to animal studies as well. This insight can contribute to furthering our understanding of the normal and diseased human brain, and to facilitate discussions between researchers from the individual disciplines

Cavitation in soft matter

Cavitation is the sudden, unstable expansion of a void or bubble within a liquid or solid subjected to a negative hydrostatic stress. Cavitation rheology is a field emerging from the development of a suite of materials characterization, damage quantification, and therapeutic techniques that exploit the physical principles of cavitation. Cavitation rheology is inherently complex and broad in scope with wide-ranging applications in the biology, chemistry, materials, and mechanics communities. This perspective aims to drive collaboration among these communities and guide discussion by defining a common core of high-priority goals while highlighting emerging opportunities in the field of cavitation rheology. A brief overview of the mechanics and dynamics of cavitation in soft matter is presented. This overview is followed by a discussion of the overarching goals of cavitation rheology and an overview of common experimental techniques. The larger unmet needs and challenges of cavitation in soft matter are then presented alongside specific opportunities for researchers from different disciplines to contribute to the field

3D fiber orientation in atherosclerotic carotid plaques

Atherosclerotic plaque rupture is the primary trigger of fatal cardiovascular events. Fibrillar collagen in atherosclerotic plaques and their directionality are anticipated to play a crucial role in plaque rupture. This study aimed assessing 3D fiber orientations and architecture in atherosclerotic plaques for the first time. Seven carotid plaques were imaged ex-vivo with a state-of-the-art Diffusion Tensor Imaging (DTI) technique, using a high magnetic field (9.4 Tesla) MRI scanner. A 3D spin-echo sequence with uni-polar diffusion sensitizing pulsed field gradients was utilized for DTI and fiber directions were assessed from diffusion tensor measurements. The distribution of the 3D fiber orientations in atherosclerotic plaques were quantified and the principal fiber orientations (circumferential, longitudinal or radial) were determined. Overall, 52% of the fiber orientations in the carotid plaque specimens were closest to the circumferential direction, 34% to the longitudinal direction, and 14% to the radial direction. Statistically no significant difference was measured in the amount of the fiber orientations between the concentric and eccentric plaque sites. However, concentric plaque sites showed a distinct structural organization, where the principally longitudinally oriented fibers were closer the luminal side and the principally circumferentially oriented fibers were located more abluminally. The acquired unique information on 3D plaque fiber direction will help understanding pathobiological mechanisms of atherosclerotic plaque progression and pave the road to more realistic biomechanical plaque modeling for rupture assessment.</p

Analysis and Visualization of Higher-Order Tensors: Using the Multipole Representation

Materialien wie Kristalle, biologisches Gewebe oder elektroaktive Polymere kommen häufig in verschiedenen Anwendung, wie dem Prothesenbau oder der Simulation von künstlicher Muskulatur vor. Diese und viele weitere Materialien haben gemeinsam, dass sie unter gewissen Umständen ihre Form und andere Materialeigenschaften ändern. Um diese Veränderung beschreiben zu können, werden, abhängig von der Anwendung, verschiedene Tensoren unterschiedlicher Ordnung benutzt. Durch die Komplexität und die starke Abhängigkeit der Tensorbedeutung von der Anwendung, gibt es bisher kein Verfahren Tensoren höherer Ordnung darzustellen, welches standardmäßig benutzt wird. Auch bezogen auf einzelne Anwendungen gibt es nur sehr wenig Arbeiten, die sich mit der visuellen Darstellung dieser Tensoren auseinandersetzt. Diese Arbeit beschäftigt sich mit diesem Problem. Es werden drei verschiedene Methoden präsentiert, Tensoren höherer Ordnung zu analysieren und zu visualisieren. Alle drei Methoden basieren auf der sogenannte deviatorischen Zerlegung und der Multipoldarstellung. Mit Hilfe der Multipole können die Symmetrien des Tensors und damit des beschriebenen Materials bestimmt werden. Diese Eigenschaft wird in für die Visualisierung des Steifigkeitstensors benutzt. Die zweite Methode basiert direkt auf den Multipolen und kann damit beliebige Tensoren in drei Dimensionen darstellen. Dieses Verfahren wird anhand des Kopplungs Tensors, ein Tensor dritter Ordnung, vorgestellt. Die ersten zwei Verfahren sind lokale Glyph-basierte Verfahren. Das dritte Verfahren ist ein erstes globales Tensorvisualisierungsverfahren, welches Tensoren beliebiger Ordnung und Symmetry in drei Dimensionen mit Hilfe eines linienbasierten Verfahrens darstellt.Materials like crystals, biological tissue or electroactive polymers are frequently used in applications like prosthesis construction or the simulation of artificial musculature. These and many other materials have in common that they change their shape and other material properties under certain circumstances. To describe these changes, different tensors of different order, dependent of the application, are used. Due to the complexity and the strong dependency of the tensor meaning of the application, there is, by now, no visualization method that is used by default. Also for specific applications there are only a few methods that address the visual analysis of higher-order tensors. This work adresses this problem. Three different methods to analyse and visualize tensors of higher order will be provided. All three methods are based on the so called deviatoric decomposition and the multipole representation. Using the multipoles the symmetries of a tensor and, therefore, of the described material, can be calculated. This property is used to visualize the stiffness tensor. The second method uses the multipoles directly and can be used for each tensor of any order in three dimensions. This method is presented by analysing the third-order coupling tensor. These two techniques are glyph-based visualization methods. The third one, a line-based method, is, according to our knowledge, a first global visualization method that can be used for an arbitrary tensor in three dimensions

Bento: a toolkit for subcellular analysis of spatial transcriptomics data

The spatial organization of molecules in a cell is essential for their functions. While current methods focus on discerning tissue architecture, cell-cell interactions, and spatial expression patterns, they are limited to the multicellular scale. We present Bento, a Python toolkit that takes advantage of single-molecule information to enable spatial analysis at the subcellular scale. Bento ingests molecular coordinates and segmentation boundaries to perform three analyses: defining subcellular domains, annotating localization patterns, and quantifying gene-gene colocalization. We demonstrate MERFISH, seqFISH + , Molecular Cartography, and Xenium datasets. Bento is part of the open-source Scverse ecosystem, enabling integration with other single-cell analysis tools