Prof. Dr. Bert Müller Department of Biomedical Engineering Profiles & Affiliations OverviewResearch Publications Projects & Collaborations Projects & Collaborations OverviewResearch Publications Projects & Collaborations Profiles & Affiliations Projects & Collaborations 28 foundShow per page10 10 20 50 X-ray imaging of the entire human brain with one micrometer resolution Research Project | 1 Project MembersImported from Grants Tool 4701396 Fluid Dynamics of the Central Nervous System: 3D Functional Anatomy & Pathophysiology in Mouse Models Research Project | 1 Project MembersNo Description available Laboratory-based phase tomography with micron resolution Research Project | 2 Project MembersNo Description available Nano Engineered Neural Interfaces - NENI Research Project | 6 Project MembersAlzheimer's disease (AD) is an irreversible, progressive neurodegenerative disease that slowly destroys memory and thinking skills eventually leading to death from complete brain failure. It is the most common cause of dementia and affects more than 46 million people globally, with 500'000 new cases diagnosed annually in the United States alone. While there is still no cure for AD, there are several prescription drugs approved by the U.S. Food and Drug Administration to treat its symptoms. Recently, there has been growing excitement around treating neurological diseases using neuromodulation techniques. Flickering strobe lights at gamma-frequency of 40 Hz have shown very promising results in mouse models where microglia immune cells could be activated and contributed to degradation of amyloid-β proteins. Invasive neuromodulation methods can target very specific areas in the brain. The current modulation devices, however, are comparable to that of early cardiac pacemakers, leading to fibrotic encapsulation within weeks. This is mainly predicated on the neural probe's mechanical properties, given by the hard platinum/iridium electrodes from the semiconductor industry. Our proposed approach for ten thousand times softer electrodes is based on nano engineered neural interfaces (NENI) - hybrid microstructured polymer pads covered by ultra-thin and soft nanostructured metal/elastomer compounds. Our NENI probes will allow a rapid reconfiguration to pre-selected brain targets for a patient-specific anatomy and therefore enable the activation of microglia immune cells. This project is in collaboration with 5 project partners from around Switzerland: University Hospital Basel, Empa, PSI, FHNW, and University of Basel. In addition, two companies: Invibio Ltd/United Kingdom, a leading provider of polymeric biomaterials which have been used in around 9 million PEEK medical implants with more than 15 years of proven clinical history and Valtronic SA, a global contract manufacturer for the electronics of medical devices, are supporting this project. Hierarchical X-ray imaging of the entire human brain Research Project | 3 Project MembersThe human brain with a weight of 1.3 kg contains around 1,000,000,000,000 cells. Current protocols for tissue imaging with cellular resolution involve optical and electron microscopies. Here, three-dimensional imaging requires serial sectioning due to the limited penetration depth. Sectioning, however, is destructive and artifact prone, with insufficient spatial resolution (perpendicular to the cuts) for visualizing cells. In the last decade, hard X-ray tomography has created virtual histology for imaging biological tissues with isotropic voxels at the micrometer scale and below. The question now arises: what is the highest achievable resolution for an atlas of the entire human brain? Currently, the best atlas is based on histological sectioning with 20 µm-wide voxels. Recent studies using synchrotron radiation-based hard X rays have imaged a full mouse brain with 0.8 µm pixel size, but the volume of a human brain is 3,000 times larger.The goal of this project is to generate an atlas of the entire human brain with 1 µm resolution. Hierarchical synchrotron radiation-based X-ray imaging will be performed at the beamline BM18 (European Synchrotron Radiation Facility - ESRF, Grenoble, France), which is under construction and will be unique with respect to beam size and transversal coherence. Here, full-field tomography of the entire human brain with voxel sizes of 20 µm and stitched local tomography acquisitions can be combined. The high-resolution imaging of the at least 12 cm-wide human brain poses several challenges, including sample preparation to withstand extreme radiation dose, acquisition protocols to keep the beamtime within limits, and data processing, which comprises slices of 100 GB and a total volume in the PB range.As the synchrotron radiation-based high-resolution X-ray measurements of the human brain can only be performed post mortem, we will make a correspondence from the ex vivo conditions back to the in vivo case in order to put this dataset into a more physiologically relevant context. Non-rigid registration of lower resolution magnetic resonance images of the human brain taken before extraction and throughout the fixation process allow for the quantification of the local deformations introduced during extraction, fixation, and embedding. In addition, the periodic high-resolution X-ray imaging of a mouse brain during the die-off process and subsequent tissue fixation and embedding will enable us to reasonably correct the brain's microanatomy. The synchrotron radiation-based X-ray imaging of the mouse brain with less than 1 µm voxel size will be carried out at the Biomedical beamline ID17 (ESRF, Grenoble, France), which is dedicated to biomedical imaging and radiation therapy.We want to make the big data yielding the microanatomy of the entire human brain freely available to the scientific community and for teaching purposes. This dataset will provide vital advances of relevance to a systems-level understanding of the human brain, maybe even close to physiological conditions. The hierarchical imaging procedure and the handling of the big imaging data is exemplary for further applications including comparatively studying entire healthy and diseased organs, industrially relevant engineering devices, and unique cultural heritage objects. AFM for nano-structural and -mechanical studies of dielectric actuators Research Project | 2 Project MembersAFM for nano-structural and -mechanical studies of dielectric actuators Multi-modal matching of two-dimensional images with three-dimensional data in the field of biomedical engineering Research Project | 3 Project MembersMulti-modal matching is understood as the automatic (elastic) alignment of data, termed regis-tration, from different imaging techniques using the characteristic anatomical features. While satisfying approaches for two-dimensional (2D) to 2D and three-dimensional (3D) to 3D data sets have been developed during the last two decades, the non-rigid 2D-3D registration belongs to the unsolved problems because of the larger degrees of freedom especially for high-resolution 'big data'. The need for 2D-3D registration, however, becomes more and more obvious, as besides the well-established histology, which highlights the functionality in tissue slices according to the selected stain, magnetic resonance (MR) and computed tomography (CT) 3D data with better and better spatial resolution and contrast have been acquired. The combination of the functional information from 2D images with the local physical quantities in 3D recorded, for example, by means of micro CT (µCT) and MR microscopy has been vital to (i) correct preparation artifacts in the histological slices applying the less detailed 3D data, to (ii) identify the issue types in 3D data using the functional information from histology in quantitative manner and to (iii) determine the optimized location and direction of histological slicing. The aim of the project is the development of algorithms for the automatic non-rigid multi-modal 2D-3D registration. Here, we will concentrate on registering histological sections with µCT-data. In a first stage, we will focus on the development of a sparse image registration approach that has the advantage of being robust and computationally efficient. The second stage uses the sparse registration as anchor points while delivering a dense multimodal registration of the two imaging modalities. Finally, the computational effort and the general usability will be optimized to allow the processing of large data sets that are characteristic for high-resolution 3D imaging in biomedical engineering. Micro- and nanoanatomy of human brain tissues Research Project | 6 Project MembersThe human body contains 10^14 cells, which are categorized into 200 to 400 cell types. The human brain accounts for about 2% of the weight of an average person. This is a much larger percentage than in other primates. Despite of its size and complexity one can reasonably assume that it is possible to reveal the individual cells within the human brain and describe its three-dimensional structure on the cellular level. To achieve this goal, we will perform grating-based hard X-ray phase tomography using synchrotron radiation facilities. In addition we will expand the available laboratory system phoenix nanotom® m from GE Healthcare by a grating interferometer. An average human cell contains 10^14 atoms, which are categorized in the 118 elements of the periodic table. Thanks to this clarity, one can reasonably expect that it is possible to reveal the nanostructure of selected pieces of brain tissues. To achieve this, we will perform spatially resolved X-ray scattering experiments at the cSAXS-beamline, Swiss Light Source at the Paul Scherrer Institut. The myelinated axons, for example, which stretch for over 10^8 m if aligned end-to-end, exhibit a quasi-periodical arrangement of the lamellar structure of the myelin sheaths repeating less than every 20 nm. This characteristic periodicity will be used to determine the abundance and the orientation of the myelin fiber bundles in projection images similar to histology and in three-dimensional space applying tomographic reconstruction techniques, which are to be further developed. The interdisciplinary project aims to bridge the gap concerning spatial resolution between the tomography data from clinical modalities (CT and MRI) and histological approaches employed by anatomists and pathologists taking advantage of recent developments in physics: X-ray scattering and phase tomography. Smart muscles for incontinence treatment (SmartSphincter) Research Project | 1 Project MembersThe aim of the proposal is to realize prototype devices acting as artificial muscle, termed anal sphincter, to finally treat patients with severe FI. The device should replace the destroyed natural muscle function using low-voltage electrically activated polymers (EAPs) controlled by implemented pressure sensors and the patient. The unique artificial fecal EAP-based sphincter system is driven by an integrated microprocessor, powered by an energy harvesting device and an implantable battery, rechargeable by transcutaneous energy transfer (TCT) controlling the fluid flow intentionally by the patient and automatically with pressure gauges. The remote control will allow the physician to perform patient-specific adjustments. Tomography of microvascular structures in murine brain tumors Research Project | 2 Project MembersThe three-dimensional vascular structures down to the smallest capillaries have been of vital interest in cancer research because of the demand for alternatives to the established treatments (surgery, medication and radiation). The present research efforts range from in vivo imaging (MRI, US, and PET), via post mortem methods, including micro computed computer tomography. In a previous study, we showed that synchrotron radiation-based necessary spatial resolution and contrast to capture the smallest vessels from casts. Tumors with damaged vessel walls are inappropriate for casting. Therefore, phase tomography was applied to visualize the capillaries. Grating-based tomography yields the necessary contrast but vessels with a diameter smaller than 20 provides the necessary spatial resolution but hardly enough contrast. Consequently, we propose first to improve the spatial resolution of grating-based tomography, second to identify rather simple in-line tomography approaches such as the one introduced by Paganin searching for better contrast, and third to combine tomograms from both approaches to gain additional information toward the smallest capillaries. 123 123 OverviewResearch Publications Projects & Collaborations
Projects & Collaborations 28 foundShow per page10 10 20 50 X-ray imaging of the entire human brain with one micrometer resolution Research Project | 1 Project MembersImported from Grants Tool 4701396 Fluid Dynamics of the Central Nervous System: 3D Functional Anatomy & Pathophysiology in Mouse Models Research Project | 1 Project MembersNo Description available Laboratory-based phase tomography with micron resolution Research Project | 2 Project MembersNo Description available Nano Engineered Neural Interfaces - NENI Research Project | 6 Project MembersAlzheimer's disease (AD) is an irreversible, progressive neurodegenerative disease that slowly destroys memory and thinking skills eventually leading to death from complete brain failure. It is the most common cause of dementia and affects more than 46 million people globally, with 500'000 new cases diagnosed annually in the United States alone. While there is still no cure for AD, there are several prescription drugs approved by the U.S. Food and Drug Administration to treat its symptoms. Recently, there has been growing excitement around treating neurological diseases using neuromodulation techniques. Flickering strobe lights at gamma-frequency of 40 Hz have shown very promising results in mouse models where microglia immune cells could be activated and contributed to degradation of amyloid-β proteins. Invasive neuromodulation methods can target very specific areas in the brain. The current modulation devices, however, are comparable to that of early cardiac pacemakers, leading to fibrotic encapsulation within weeks. This is mainly predicated on the neural probe's mechanical properties, given by the hard platinum/iridium electrodes from the semiconductor industry. Our proposed approach for ten thousand times softer electrodes is based on nano engineered neural interfaces (NENI) - hybrid microstructured polymer pads covered by ultra-thin and soft nanostructured metal/elastomer compounds. Our NENI probes will allow a rapid reconfiguration to pre-selected brain targets for a patient-specific anatomy and therefore enable the activation of microglia immune cells. This project is in collaboration with 5 project partners from around Switzerland: University Hospital Basel, Empa, PSI, FHNW, and University of Basel. In addition, two companies: Invibio Ltd/United Kingdom, a leading provider of polymeric biomaterials which have been used in around 9 million PEEK medical implants with more than 15 years of proven clinical history and Valtronic SA, a global contract manufacturer for the electronics of medical devices, are supporting this project. Hierarchical X-ray imaging of the entire human brain Research Project | 3 Project MembersThe human brain with a weight of 1.3 kg contains around 1,000,000,000,000 cells. Current protocols for tissue imaging with cellular resolution involve optical and electron microscopies. Here, three-dimensional imaging requires serial sectioning due to the limited penetration depth. Sectioning, however, is destructive and artifact prone, with insufficient spatial resolution (perpendicular to the cuts) for visualizing cells. In the last decade, hard X-ray tomography has created virtual histology for imaging biological tissues with isotropic voxels at the micrometer scale and below. The question now arises: what is the highest achievable resolution for an atlas of the entire human brain? Currently, the best atlas is based on histological sectioning with 20 µm-wide voxels. Recent studies using synchrotron radiation-based hard X rays have imaged a full mouse brain with 0.8 µm pixel size, but the volume of a human brain is 3,000 times larger.The goal of this project is to generate an atlas of the entire human brain with 1 µm resolution. Hierarchical synchrotron radiation-based X-ray imaging will be performed at the beamline BM18 (European Synchrotron Radiation Facility - ESRF, Grenoble, France), which is under construction and will be unique with respect to beam size and transversal coherence. Here, full-field tomography of the entire human brain with voxel sizes of 20 µm and stitched local tomography acquisitions can be combined. The high-resolution imaging of the at least 12 cm-wide human brain poses several challenges, including sample preparation to withstand extreme radiation dose, acquisition protocols to keep the beamtime within limits, and data processing, which comprises slices of 100 GB and a total volume in the PB range.As the synchrotron radiation-based high-resolution X-ray measurements of the human brain can only be performed post mortem, we will make a correspondence from the ex vivo conditions back to the in vivo case in order to put this dataset into a more physiologically relevant context. Non-rigid registration of lower resolution magnetic resonance images of the human brain taken before extraction and throughout the fixation process allow for the quantification of the local deformations introduced during extraction, fixation, and embedding. In addition, the periodic high-resolution X-ray imaging of a mouse brain during the die-off process and subsequent tissue fixation and embedding will enable us to reasonably correct the brain's microanatomy. The synchrotron radiation-based X-ray imaging of the mouse brain with less than 1 µm voxel size will be carried out at the Biomedical beamline ID17 (ESRF, Grenoble, France), which is dedicated to biomedical imaging and radiation therapy.We want to make the big data yielding the microanatomy of the entire human brain freely available to the scientific community and for teaching purposes. This dataset will provide vital advances of relevance to a systems-level understanding of the human brain, maybe even close to physiological conditions. The hierarchical imaging procedure and the handling of the big imaging data is exemplary for further applications including comparatively studying entire healthy and diseased organs, industrially relevant engineering devices, and unique cultural heritage objects. AFM for nano-structural and -mechanical studies of dielectric actuators Research Project | 2 Project MembersAFM for nano-structural and -mechanical studies of dielectric actuators Multi-modal matching of two-dimensional images with three-dimensional data in the field of biomedical engineering Research Project | 3 Project MembersMulti-modal matching is understood as the automatic (elastic) alignment of data, termed regis-tration, from different imaging techniques using the characteristic anatomical features. While satisfying approaches for two-dimensional (2D) to 2D and three-dimensional (3D) to 3D data sets have been developed during the last two decades, the non-rigid 2D-3D registration belongs to the unsolved problems because of the larger degrees of freedom especially for high-resolution 'big data'. The need for 2D-3D registration, however, becomes more and more obvious, as besides the well-established histology, which highlights the functionality in tissue slices according to the selected stain, magnetic resonance (MR) and computed tomography (CT) 3D data with better and better spatial resolution and contrast have been acquired. The combination of the functional information from 2D images with the local physical quantities in 3D recorded, for example, by means of micro CT (µCT) and MR microscopy has been vital to (i) correct preparation artifacts in the histological slices applying the less detailed 3D data, to (ii) identify the issue types in 3D data using the functional information from histology in quantitative manner and to (iii) determine the optimized location and direction of histological slicing. The aim of the project is the development of algorithms for the automatic non-rigid multi-modal 2D-3D registration. Here, we will concentrate on registering histological sections with µCT-data. In a first stage, we will focus on the development of a sparse image registration approach that has the advantage of being robust and computationally efficient. The second stage uses the sparse registration as anchor points while delivering a dense multimodal registration of the two imaging modalities. Finally, the computational effort and the general usability will be optimized to allow the processing of large data sets that are characteristic for high-resolution 3D imaging in biomedical engineering. Micro- and nanoanatomy of human brain tissues Research Project | 6 Project MembersThe human body contains 10^14 cells, which are categorized into 200 to 400 cell types. The human brain accounts for about 2% of the weight of an average person. This is a much larger percentage than in other primates. Despite of its size and complexity one can reasonably assume that it is possible to reveal the individual cells within the human brain and describe its three-dimensional structure on the cellular level. To achieve this goal, we will perform grating-based hard X-ray phase tomography using synchrotron radiation facilities. In addition we will expand the available laboratory system phoenix nanotom® m from GE Healthcare by a grating interferometer. An average human cell contains 10^14 atoms, which are categorized in the 118 elements of the periodic table. Thanks to this clarity, one can reasonably expect that it is possible to reveal the nanostructure of selected pieces of brain tissues. To achieve this, we will perform spatially resolved X-ray scattering experiments at the cSAXS-beamline, Swiss Light Source at the Paul Scherrer Institut. The myelinated axons, for example, which stretch for over 10^8 m if aligned end-to-end, exhibit a quasi-periodical arrangement of the lamellar structure of the myelin sheaths repeating less than every 20 nm. This characteristic periodicity will be used to determine the abundance and the orientation of the myelin fiber bundles in projection images similar to histology and in three-dimensional space applying tomographic reconstruction techniques, which are to be further developed. The interdisciplinary project aims to bridge the gap concerning spatial resolution between the tomography data from clinical modalities (CT and MRI) and histological approaches employed by anatomists and pathologists taking advantage of recent developments in physics: X-ray scattering and phase tomography. Smart muscles for incontinence treatment (SmartSphincter) Research Project | 1 Project MembersThe aim of the proposal is to realize prototype devices acting as artificial muscle, termed anal sphincter, to finally treat patients with severe FI. The device should replace the destroyed natural muscle function using low-voltage electrically activated polymers (EAPs) controlled by implemented pressure sensors and the patient. The unique artificial fecal EAP-based sphincter system is driven by an integrated microprocessor, powered by an energy harvesting device and an implantable battery, rechargeable by transcutaneous energy transfer (TCT) controlling the fluid flow intentionally by the patient and automatically with pressure gauges. The remote control will allow the physician to perform patient-specific adjustments. Tomography of microvascular structures in murine brain tumors Research Project | 2 Project MembersThe three-dimensional vascular structures down to the smallest capillaries have been of vital interest in cancer research because of the demand for alternatives to the established treatments (surgery, medication and radiation). The present research efforts range from in vivo imaging (MRI, US, and PET), via post mortem methods, including micro computed computer tomography. In a previous study, we showed that synchrotron radiation-based necessary spatial resolution and contrast to capture the smallest vessels from casts. Tumors with damaged vessel walls are inappropriate for casting. Therefore, phase tomography was applied to visualize the capillaries. Grating-based tomography yields the necessary contrast but vessels with a diameter smaller than 20 provides the necessary spatial resolution but hardly enough contrast. Consequently, we propose first to improve the spatial resolution of grating-based tomography, second to identify rather simple in-line tomography approaches such as the one introduced by Paganin searching for better contrast, and third to combine tomograms from both approaches to gain additional information toward the smallest capillaries. 123 123
X-ray imaging of the entire human brain with one micrometer resolution Research Project | 1 Project MembersImported from Grants Tool 4701396
Fluid Dynamics of the Central Nervous System: 3D Functional Anatomy & Pathophysiology in Mouse Models Research Project | 1 Project MembersNo Description available
Laboratory-based phase tomography with micron resolution Research Project | 2 Project MembersNo Description available
Nano Engineered Neural Interfaces - NENI Research Project | 6 Project MembersAlzheimer's disease (AD) is an irreversible, progressive neurodegenerative disease that slowly destroys memory and thinking skills eventually leading to death from complete brain failure. It is the most common cause of dementia and affects more than 46 million people globally, with 500'000 new cases diagnosed annually in the United States alone. While there is still no cure for AD, there are several prescription drugs approved by the U.S. Food and Drug Administration to treat its symptoms. Recently, there has been growing excitement around treating neurological diseases using neuromodulation techniques. Flickering strobe lights at gamma-frequency of 40 Hz have shown very promising results in mouse models where microglia immune cells could be activated and contributed to degradation of amyloid-β proteins. Invasive neuromodulation methods can target very specific areas in the brain. The current modulation devices, however, are comparable to that of early cardiac pacemakers, leading to fibrotic encapsulation within weeks. This is mainly predicated on the neural probe's mechanical properties, given by the hard platinum/iridium electrodes from the semiconductor industry. Our proposed approach for ten thousand times softer electrodes is based on nano engineered neural interfaces (NENI) - hybrid microstructured polymer pads covered by ultra-thin and soft nanostructured metal/elastomer compounds. Our NENI probes will allow a rapid reconfiguration to pre-selected brain targets for a patient-specific anatomy and therefore enable the activation of microglia immune cells. This project is in collaboration with 5 project partners from around Switzerland: University Hospital Basel, Empa, PSI, FHNW, and University of Basel. In addition, two companies: Invibio Ltd/United Kingdom, a leading provider of polymeric biomaterials which have been used in around 9 million PEEK medical implants with more than 15 years of proven clinical history and Valtronic SA, a global contract manufacturer for the electronics of medical devices, are supporting this project.
Hierarchical X-ray imaging of the entire human brain Research Project | 3 Project MembersThe human brain with a weight of 1.3 kg contains around 1,000,000,000,000 cells. Current protocols for tissue imaging with cellular resolution involve optical and electron microscopies. Here, three-dimensional imaging requires serial sectioning due to the limited penetration depth. Sectioning, however, is destructive and artifact prone, with insufficient spatial resolution (perpendicular to the cuts) for visualizing cells. In the last decade, hard X-ray tomography has created virtual histology for imaging biological tissues with isotropic voxels at the micrometer scale and below. The question now arises: what is the highest achievable resolution for an atlas of the entire human brain? Currently, the best atlas is based on histological sectioning with 20 µm-wide voxels. Recent studies using synchrotron radiation-based hard X rays have imaged a full mouse brain with 0.8 µm pixel size, but the volume of a human brain is 3,000 times larger.The goal of this project is to generate an atlas of the entire human brain with 1 µm resolution. Hierarchical synchrotron radiation-based X-ray imaging will be performed at the beamline BM18 (European Synchrotron Radiation Facility - ESRF, Grenoble, France), which is under construction and will be unique with respect to beam size and transversal coherence. Here, full-field tomography of the entire human brain with voxel sizes of 20 µm and stitched local tomography acquisitions can be combined. The high-resolution imaging of the at least 12 cm-wide human brain poses several challenges, including sample preparation to withstand extreme radiation dose, acquisition protocols to keep the beamtime within limits, and data processing, which comprises slices of 100 GB and a total volume in the PB range.As the synchrotron radiation-based high-resolution X-ray measurements of the human brain can only be performed post mortem, we will make a correspondence from the ex vivo conditions back to the in vivo case in order to put this dataset into a more physiologically relevant context. Non-rigid registration of lower resolution magnetic resonance images of the human brain taken before extraction and throughout the fixation process allow for the quantification of the local deformations introduced during extraction, fixation, and embedding. In addition, the periodic high-resolution X-ray imaging of a mouse brain during the die-off process and subsequent tissue fixation and embedding will enable us to reasonably correct the brain's microanatomy. The synchrotron radiation-based X-ray imaging of the mouse brain with less than 1 µm voxel size will be carried out at the Biomedical beamline ID17 (ESRF, Grenoble, France), which is dedicated to biomedical imaging and radiation therapy.We want to make the big data yielding the microanatomy of the entire human brain freely available to the scientific community and for teaching purposes. This dataset will provide vital advances of relevance to a systems-level understanding of the human brain, maybe even close to physiological conditions. The hierarchical imaging procedure and the handling of the big imaging data is exemplary for further applications including comparatively studying entire healthy and diseased organs, industrially relevant engineering devices, and unique cultural heritage objects.
AFM for nano-structural and -mechanical studies of dielectric actuators Research Project | 2 Project MembersAFM for nano-structural and -mechanical studies of dielectric actuators
Multi-modal matching of two-dimensional images with three-dimensional data in the field of biomedical engineering Research Project | 3 Project MembersMulti-modal matching is understood as the automatic (elastic) alignment of data, termed regis-tration, from different imaging techniques using the characteristic anatomical features. While satisfying approaches for two-dimensional (2D) to 2D and three-dimensional (3D) to 3D data sets have been developed during the last two decades, the non-rigid 2D-3D registration belongs to the unsolved problems because of the larger degrees of freedom especially for high-resolution 'big data'. The need for 2D-3D registration, however, becomes more and more obvious, as besides the well-established histology, which highlights the functionality in tissue slices according to the selected stain, magnetic resonance (MR) and computed tomography (CT) 3D data with better and better spatial resolution and contrast have been acquired. The combination of the functional information from 2D images with the local physical quantities in 3D recorded, for example, by means of micro CT (µCT) and MR microscopy has been vital to (i) correct preparation artifacts in the histological slices applying the less detailed 3D data, to (ii) identify the issue types in 3D data using the functional information from histology in quantitative manner and to (iii) determine the optimized location and direction of histological slicing. The aim of the project is the development of algorithms for the automatic non-rigid multi-modal 2D-3D registration. Here, we will concentrate on registering histological sections with µCT-data. In a first stage, we will focus on the development of a sparse image registration approach that has the advantage of being robust and computationally efficient. The second stage uses the sparse registration as anchor points while delivering a dense multimodal registration of the two imaging modalities. Finally, the computational effort and the general usability will be optimized to allow the processing of large data sets that are characteristic for high-resolution 3D imaging in biomedical engineering.
Micro- and nanoanatomy of human brain tissues Research Project | 6 Project MembersThe human body contains 10^14 cells, which are categorized into 200 to 400 cell types. The human brain accounts for about 2% of the weight of an average person. This is a much larger percentage than in other primates. Despite of its size and complexity one can reasonably assume that it is possible to reveal the individual cells within the human brain and describe its three-dimensional structure on the cellular level. To achieve this goal, we will perform grating-based hard X-ray phase tomography using synchrotron radiation facilities. In addition we will expand the available laboratory system phoenix nanotom® m from GE Healthcare by a grating interferometer. An average human cell contains 10^14 atoms, which are categorized in the 118 elements of the periodic table. Thanks to this clarity, one can reasonably expect that it is possible to reveal the nanostructure of selected pieces of brain tissues. To achieve this, we will perform spatially resolved X-ray scattering experiments at the cSAXS-beamline, Swiss Light Source at the Paul Scherrer Institut. The myelinated axons, for example, which stretch for over 10^8 m if aligned end-to-end, exhibit a quasi-periodical arrangement of the lamellar structure of the myelin sheaths repeating less than every 20 nm. This characteristic periodicity will be used to determine the abundance and the orientation of the myelin fiber bundles in projection images similar to histology and in three-dimensional space applying tomographic reconstruction techniques, which are to be further developed. The interdisciplinary project aims to bridge the gap concerning spatial resolution between the tomography data from clinical modalities (CT and MRI) and histological approaches employed by anatomists and pathologists taking advantage of recent developments in physics: X-ray scattering and phase tomography.
Smart muscles for incontinence treatment (SmartSphincter) Research Project | 1 Project MembersThe aim of the proposal is to realize prototype devices acting as artificial muscle, termed anal sphincter, to finally treat patients with severe FI. The device should replace the destroyed natural muscle function using low-voltage electrically activated polymers (EAPs) controlled by implemented pressure sensors and the patient. The unique artificial fecal EAP-based sphincter system is driven by an integrated microprocessor, powered by an energy harvesting device and an implantable battery, rechargeable by transcutaneous energy transfer (TCT) controlling the fluid flow intentionally by the patient and automatically with pressure gauges. The remote control will allow the physician to perform patient-specific adjustments.
Tomography of microvascular structures in murine brain tumors Research Project | 2 Project MembersThe three-dimensional vascular structures down to the smallest capillaries have been of vital interest in cancer research because of the demand for alternatives to the established treatments (surgery, medication and radiation). The present research efforts range from in vivo imaging (MRI, US, and PET), via post mortem methods, including micro computed computer tomography. In a previous study, we showed that synchrotron radiation-based necessary spatial resolution and contrast to capture the smallest vessels from casts. Tumors with damaged vessel walls are inappropriate for casting. Therefore, phase tomography was applied to visualize the capillaries. Grating-based tomography yields the necessary contrast but vessels with a diameter smaller than 20 provides the necessary spatial resolution but hardly enough contrast. Consequently, we propose first to improve the spatial resolution of grating-based tomography, second to identify rather simple in-line tomography approaches such as the one introduced by Paganin searching for better contrast, and third to combine tomograms from both approaches to gain additional information toward the smallest capillaries.
