Periodic Reporting for period 4 - C-MORPH (Noninvasive cell specific morphometry in neuroinflammation and degeneration)
Berichtszeitraum: 2023-06-01 bis 2025-01-31
Brain structure determines function. Disentangling regional microstructural properties and understanding how these properties constitute brain function is a central goal of neuroimaging of the human brain and a key prerequisite for a mechanistic understanding of brain diseases and their treatment. Previous studies using magnetic resonance (MR) imaging have established links between regional brain microstructure and inter- individual variation in brain function, but this line of research has been limited by the non-specificity of MR-derived markers. This hampers the application of MR imaging as a tool to identify specific fingerprints of the underlying disease process.
Neurodegenerative and neuroinflammatory diseases, such as Multiple Sclerosis, impair the quality of life for the diseased and their families and pose a big cost for society. Better and more precise
In this project, we advance methodology on state-of-the-art MR hardware and harvest the synergy of these methods to realize Cell-specific in vivo MORPHometry (C-MORPH) of the intact human brain and spinal cord. In focus is the hybrid of advanced diffusion encoding strategies, spectroscopy and novel imaging approaches. Our aim is to establish methods and analyses to derive cell-type specific tissue properties in the healthy and diseased brain. In particular, we aim for isolating the severity of specific pathological processes and their development over time. To date, such processes are more or less superimposed in conventional clinical imaging data. Once validated, the experimental methods and analyses will be simplified and adapted to provide clinically applicable tools. This will push the frontiers of MR-based personalized medicine, guiding therapeutic decisions by providing sensitive probes of cell-specific microstructural changes caused by inflammation, neurodegeneration or treatment response.
Neurodegenerative and neuroinflammatory diseases, such as Multiple Sclerosis, impair the quality of life for the diseased and their families and pose a big cost for society. Better and more precise
In this project, we advance methodology on state-of-the-art MR hardware and harvest the synergy of these methods to realize Cell-specific in vivo MORPHometry (C-MORPH) of the intact human brain and spinal cord. In focus is the hybrid of advanced diffusion encoding strategies, spectroscopy and novel imaging approaches. Our aim is to establish methods and analyses to derive cell-type specific tissue properties in the healthy and diseased brain. In particular, we aim for isolating the severity of specific pathological processes and their development over time. To date, such processes are more or less superimposed in conventional clinical imaging data. Once validated, the experimental methods and analyses will be simplified and adapted to provide clinically applicable tools. This will push the frontiers of MR-based personalized medicine, guiding therapeutic decisions by providing sensitive probes of cell-specific microstructural changes caused by inflammation, neurodegeneration or treatment response.
Initial work has been performed on building up theory and analysis for our new approaches. Experimental work has been performed on preclinical systems demonstrating a new contrast mechanism in brain imaging. As a spin off we have engaged collaborators to adapt our techniques for work in tissue outside the brain which is work currently in progress.
We are in the ongoing work exploring the translation of these techniques to human applications which will fuel our final goal of characterising neurodegeneration and inflammation in individuals with multiple sclerosis.
We are in the ongoing work exploring the translation of these techniques to human applications which will fuel our final goal of characterising neurodegeneration and inflammation in individuals with multiple sclerosis.
This project has provided new tools for characterising and isolating effects for disentangling structural features of cells in biological tissue with particular focus on neuronal tissue. Our work on spectrally modulated gradients demonstrate how our novel independent contrast mechanisms can provide simultaneous differentiation of shape and size of structures on a µm length scale.
Beyond the planned method development, or work has lead to the discovery of a new effect. We have in within the project explored a new concept for microstructural imaging with diffusion weighted magnetic resonance imaging called spectral anisotropy. This concept was first presented in a book chapter and we have subsequent peer reviewed conference contributions investigated this phenomenon first in theory, with simulations and in very recent work also shown the effects in experimental data for the first time. We are currently exploring to what extent we can add this additional information to upcoming studies in patients.
We have further in proof of concept work demonstrated that our methods also provide a useful contrats in heart tissue which we anticipate will further increase the value of the methods developed within the project.
Beyond the planned method development, or work has lead to the discovery of a new effect. We have in within the project explored a new concept for microstructural imaging with diffusion weighted magnetic resonance imaging called spectral anisotropy. This concept was first presented in a book chapter and we have subsequent peer reviewed conference contributions investigated this phenomenon first in theory, with simulations and in very recent work also shown the effects in experimental data for the first time. We are currently exploring to what extent we can add this additional information to upcoming studies in patients.
We have further in proof of concept work demonstrated that our methods also provide a useful contrats in heart tissue which we anticipate will further increase the value of the methods developed within the project.