Multiscale Imaging //
Science

Scope

Our group is a multidisciplinary team which is interested in the application and combination of multiscale imaging modalities. Our overall aim is to assess complex patterns of pathological tissue alterations in the brain using advanced magnetic resonance (MRI) techniques, and modern histopathological methods.

During neurodegenerative disease, or after brain injury, several pathological processes take place in the brain, such as neurodegeneration, inflammation, plasticity, axonal injury, or demyelination, which alter the brain tissue microenvironment. These microstructural changes can be detected by MRI. However, there is a lack of understanding of how specific tissue substrates affect the MRI contrast. This knowledge is crucial to identify biomarkers for early diagnosis, prediction of outcomes, and guidance for development of novel treatment strategies of neurodegenerative diseases and brain damage.

Research interests

  • To apply advance MRI techniques and analysis methods to animal models of disease.
  • To characterize underlying MRI changes in brain tissue using advanced microscopic techniques.
  • To integrate microstructural damage information to assess alterations of the brain network.

Methodological approach

Advanced diffusion magnetic resonance imaging (MRI) techniques and analyses: Non-invasive MRI techniques may provide imaging markers which are increasingly valuable for making robust pre¬dictions of clinical outcome of patients. Our work has been focused to explore the potential of more advanced MRI methods which might provide new insights into the non-invasive detection of the brain pathology. Furthermore, we utilize new analyses tools to find new ways of studying the alterations in the brain network.

We have extensively applied diffusion MRI techniques, such as diffusion tensor imaging (DTI), in the study of potential biomarkers for epileptogenesis in animal models of epilepsy and traumatic brain injury. DTI is the gold standard to image tissue microstructure, and moreover, fiber tracking of white matter. Recently, we implemented more advanced diffusion acquisitions and data analyses which receive the generic name of high-angular-resolution diffusion imaging (HARDI). HARDI can resolve multiple intravoxel populations with different orientations. More accurate estimate fiber orientation distribution functions (ODFs) improves tractography methods, and may give more info from tissue microstructure in normal and pathological brain. Additionally to these approaches, we are currently exploring the potential of super-resolution techniques, such as track-density imaging (TDI), high-spatial-resolution and outstanding anatomical contrast at both, microscopic and large scales. 

Histology and 3D electron microscopy: Even though advanced MRI methodologies are promising tools to be used in the clinic, their application is limited because of their ambiguous biological interpretation. For that, we investigate underlying microstructural substrates responsible of MRI changes using light and electron microscopy. Using histochemistry and immunohistochemistry, we assess alterations in the cytoarchitecture and myeloarchitecture of the brain tissue, as well as axonal and cytoskeletal damage, inflammation, or plasticity after brain injury. These processes are able to alter the microstructural environment detectable by DTI or HARDI.

A step forward in the characterization of the MRI contrast is to extract information at the level of the MRI voxel. For that, we applied a more advanced microscopic technique, serial block-face scanning electron microscopy (SBEM), which produces 3D visualization of tissue microstructure in high resolution (~50 nm) at mesoscopic scale (few hundreds µm). Currently, we develop automatic segmentation strategies to extract information of individual cellular components of the tissue. Furthermore, we develop quantitative mathematical tools based on Fourier, structure tensor and Monte Carlo random walk simulation approaches to extract 3D metrics from SBEM data sets which can be directly comparable to DTI and HARDI data. Altogether, this may provide further understanding of the complex relationships between MRI measurements and the pathological effects in the brain.

Funding

Academy of Finland, Jane and Aatos Erkko Foundation, National Institutes of Health (NIH), and Doctoral Program in Molecular Medicine (UEF).

Selected publications

  1. DeepACSON: Automated White Matter Segmentation. A. Abdollahzadeh, I. Belevich, E. Jokitalo, A. Sierra and J. Tohka. BioRxiv 2019;828541; doi: https://doi.org/10.1101/828541.
  2. Cylindrical Shape Decomposition Algorithm for 3D Segmentation. A. Abdollahzadeh, A. Sierra and J. Tohka. ArXiv 2019;1911.00571;  doi: https://arxiv.org/abs/1911.00571.
  3. Automated 3D Axonal Morphometry of White Matter. A. Abdollahzadeh, I. Belevich, E. Jokitalo, J. Tohka, and A. Sierra. Sci Rep. 2019 Apr 15;9(1):6084.
  4. Quantification of anisotropy and orientation in 3D electron microscopy and diffusion tensor imaging in injured rat brain. R.A. Salo, I. Belevich, E. Jokitalo, O. Gröhn, and A. Sierra. Neuroimage. 2018 May 15;172:404-414.
  5. Quantitative susceptibility mapping reveals thalamic nuclei-specific deposits of iron and calcium in the rat brain after status epilepticus. M. Aggarwal, X. Li, O. Gröhn and A. Sierra. J Magn Reson Imaging. Jun 5, 2017.
  6. In vivo characterization of microstructural changes during epileptogenesis by high resolution diffusion tensor imaging of rat hippocampal subfields. R. Salo, T. Miettinen, T. Laitinen, O. Gröhn and A. Sierra. Neuroimage. 4;152:221-236, 2017.
  7. Magnetization transfer SWIFT MRI consistently detects histologically verified myelin loss in the thalamocortical pathway after a traumatic brain injury in rat. L.J. Lehto, A. Sierra and O. Gröhn. NMR Biomed. 30(2), 2017.
  8. Imaging of microstructural damage and plasticity in the hippocampus during epileptogenesis. A. Sierra, O. Gröhn and A. Pitkänen. Neuroscience 2015 Apr 28.
  9. Diffusion tensor imaging of hippocampal network plasticity. A. Sierra, T. Laitinen, O. Gröhn and A. Pitkänen. Brain Struct Funct. 2015 Mar;220(2):781-801.
  10. Diffusion Tensor MRI of axonal plasticity in the rat hippocampus. T. Laitinen, A. Sierra, A. Pitkänen, and O. Gröhn. NeuroImage. 2010 Jun;51(2):521-30.