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Polarised light imaging (PLI) utilises the birefringence of the myelin sheaths in order to visualise the orientation of nerve fibres in microtome sections of adult human post-mortem brains at ultra-high spatial resolution. The preparation of post-mortem brains for PLI involves fixation, freezing and cutting into 100-μm-thick sections. Hence, geometrical distortions of histological sections are inevitable and have to be removed for 3D reconstruction and subsequent fibre tracking. We here present a processing pipeline for 3D reconstruction of these sections using PLI derived multimodal images of post-mortem brains. Blockface images of the brains were obtained during cutting; they serve as reference data for alignment and elimination of distortion artefacts. In addition to the spatial image transformation, fibre orientation vectors were reoriented using the transformation fields, which consider both affine and subsequent non-linear registration. The application of this registration and reorientation approach results in a smooth fibre vector field, which reflects brain morphology. PLI combined with 3D reconstruction and fibre tracking is a powerful tool for human brain mapping. It can also serve as an independent method for evaluating in vivo fibre tractography.
Signal transmission between different brain regions requires connecting fiber tracts, the structural basis of the human connectome. In contrast to animal brains, where a multitude of tract tracing methods can be used, magnetic resonance (MR)-based diffusion imaging is presently the only promising approach to study fiber tracts between specific human brain regions. However, this procedure has various inherent restrictions caused by its relatively low spatial resolution. Here, we introduce 3D-polarized light imaging (3D-PLI) to map the three-dimensional course of fiber tracts in the human brain with a resolution at a submillimeter scale based on a voxel size of 100 μm isotropic or less. 3D-PLI demonstrates nerve fibers by utilizing their intrinsic birefringence of myelin sheaths surrounding axons. This optical method enables the demonstration of 3D fiber orientations in serial microtome sections of entire human brains. Examples for the feasibility of this novel approach are given here. 3D-PLI enables the study of brain regions of intense fiber crossing in unprecedented detail, and provides an independent evaluation of fiber tracts derived from diffusion imaging data.
Mass spectrometric imaging (MSI) is a young innovative analytical technique and combines different fields of advanced mass spectrometry and biomedical research with the aim to provide maps of elements and molecules, complexes or fragments. Especially essential metals such as zinc, copper, iron and manganese play a functional role in signaling, metabolism and homeostasis of the cell. Due to the high degree of spatial organization of metals in biological systems their distribution analysis is of key interest in life sciences. We have developed analytical techniques termed BrainMet using laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) imaging to measure the distribution of trace metals in biological tissues for biomedical research and feasibility studies—including bioaccumulation and bioavailability studies, ecological risk assessment and toxicity studies in humans and other organisms. The analytical BrainMet techniques provide quantitative images of metal distributions in brain tissue slices which can be combined with other imaging modalities such as photomicrography of native or processed tissue (histochemistry, immunostaining) and autoradiography or with in vivo techniques such as positron emission tomography or magnetic resonance tomography.
Prospective and instrumental developments will be discussed concerning the development of the metalloprotein microscopy using a laser microdissection (LMD) apparatus for specific sample introduction into an inductively coupled plasma mass spectrometer (LMD-ICP-MS) or an application of the near field effect in LA-ICP-MS (NF-LA-ICP-MS). These nano-scale mass spectrometric techniques provide improved spatial resolution down to the single cell level.
Metals are involved in many processes of life. They are needed for enzymatic reactions, are involved in healthy processes but also yield diseases if the metal homeostasis is disordered. Therefore, the interest to assess the spatial distribution of metals is rising in biomedical science. Imaging metal (and non-metal) isotopes by laser ablation mass spectrometry with inductively coupled plasma (LA-ICP-MS) requires a special software solution to process raw data obtained by scanning a sample line-by-line. As no software ready to use was available we developed an interactive software tool for Image Generation and Analysis (IMAGENA). Unless optimised for LA-ICP-MS, IMAGENA can handle other raw data as well. The general purpose was to reconstruct images from a continuous list of raw data points, to visualise these images, and to convert them into a commonly readable image file format that can be further analysed by standard image analysis software. The generation of the image starts with loading a text file that holds a data column of every measured isotope. Specifying general spatial domain settings like the data offset and the image dimensions is done by the user getting a direct feedback by means of a preview image. IMAGENA provides tools for calibration and to correct for a signal drift in the y-direction. Images are visualised in greyscale as well a pseudo-colours with possibilities for contrast enhancement. Image analysis is performed in terms of smoothed line plots in row and column direction.
Biological applications like vesicle membrane analysis involve the precise segmentation of 3D structures in noisy volumetric data, obtained by techniques like magnetic resonance imaging (MRI) or laser scanning microscopy (LSM). Dealing with such data is a challenging task and requires robust and accurate segmentation methods. In this article, we propose a novel energy model for 3D segmentation fusing various cues like regional intensity subdivision, edge alignment and orientation information. The uniqueness of the approach consists in the definition of a new anisotropic regularizer, which accounts for the unbalanced slicing of the measured volume data, and the generalization of an efficient numerical scheme for solving the arising minimization problem, based on linearization and fixed-point iteration. We show how the proposed energy model can be optimized globally by making use of recent continuous convex relaxation techniques. The accuracy and robustness of the presented approach are demonstrated by evaluating it on multiple real data sets and comparing it to alternative segmentation methods based on level sets. Although the proposed model is designed with focus on the particular application at hand, it is general enough to be applied to a variety of different segmentation tasks.
GraphMIC is a cross-platform image processing application utilizing the libraries ITK and OpenCV. The abstract structure of image processing pipelines is visually represented by user interface components based on modern QtQuick technology and allows users to focus on arrangement and parameterization of operations rather than implementing the equivalent functionality natively in C++. The application's central goal is to improve and simplify the typical workflow by providing various high level features and functions like multi threading, image sequence processing and advanced error handling. A built-in python interpreter allows the creation of custom nodes, where user defined algorithms can be integrated to extend basic functionality. An embedded 2d/3d visual-izer gives feedback of the resulting image of an operation or the whole pipeline. User inputs like seed points, contours or regions are forwarded to the processing pipeline as parameters to offer semi-automatic image computing. We report the main concept of the application and introduce several features and their implementation. Finally, the current state of development as well as future perspectives of GraphMIC are discussed
Despite multimodal treatment, the prognosis of high-grade gliomas is grim. As tumor growth is critically dependent on new blood vessel formation, antiangiogenic treatment approaches offer an innovative treatment strategy. Bevacizumab, a humanized monoclonal antibody, has been in the spotlight of antiangiogenic approaches for several years. Currently, MRI including contrast-enhanced T1-weighted and T2/fluid-attenuated inversion recovery (FLAIR) images is routinely used to evaluate antiangiogenic treatment response (Response Assessment in Neuro-Oncology criteria). However, by restoring the blood–brain barrier, bevacizumab may reduce T1 contrast enhancement and T2/FLAIR hyperintensity, thereby obscuring the imaging-based detection of progression. The aim of this review is to highlight the recent role of imaging biomarkers from MR and PET imaging on measurement of disease progression and treatment effectiveness in antiangiogenic therapies. Based on the reviewed studies, multimodal imaging combining standard MRI with new physiological MRI techniques and metabolic PET imaging, in particular amino acid tracers, may have the ability to detect antiangiogenic drug susceptibility or resistance prior to morphological changes. As advances occur in the development of therapies that target specific biochemical or molecular pathways and alter tumor physiology in potentially predictable ways, the validation of physiological and metabolic imaging biomarkers will become increasingly important in the near future.
Medical image processing provides core innovation for medical imaging. This paper is focused on recent developments from science to applications analyzing the past fifteen years of history of the proceedings of the German annual meeting on medical image processing (BVM). Furthermore, some members of the program committee present their personal points of views: (i) multi-modality for imaging and diagnosis, (ii) analysis of diffusion-weighted imaging, (iii) model-based image analysis, (iv) registration of section images, (v) from images to information in digital endoscopy, and (vi) virtual reality and robotics. Medical imaging and medical image computing is seen as field of rapid development with clear trends to integrated applications in diagnostics, treatment planning and treatment.