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Doctoral defence of Isabel San Martin Molina, MSc, 5 Dec 2023: A multiscale imaging approach to assess subtle brain damage experimentally

The doctoral dissertation in the field of Biomedical Imaging will be examined at the Faculty of Health Sciences at Kuopio campus. The public examination will be streamed online.

What is the topic of your doctoral research? Why is it important to study the topic?

Brain damage is a common health and economic problem worldwide. Many individuals do not receive medical attention due to the lack of biomarkers. Conventional magnetic resonance imaging (MRI) techniques used in clinics cannot detect subtle structural and functional changes after brain damage, leading to long-term consequences for patients. Therefore, this thesis assesses the potential and limitations of advanced non-invasive MRI such as diffusion tensor imaging (DTI) to investigate microstructural changes in brain damage pathology. The goal is to shed light on the mechanisms connecting DTI and tissue pathological changes in two conditions: mild traumatic brain injury (mTBI) and epilepsy. To achieve this, a multimodal imaging approach is employed by using light microscopy and scanning micro-X-ray diffraction (SμXRD), aiming to provide a comprehensive understanding of the relationship between DTI findings and the underlying tissue alterations in these conditions in rats. The integration of multiscale tissue information using this multimodal imaging approach provides valuable insights into the pathophysiology of brain damage and will improve diagnostic and treatment strategies, ultimately reducing the consequences of brain damage.

What are the key findings or observations of your doctoral research?

This thesis offers new possibilities for studying tissue damage and interpreting DTI imaging results in future research. It provides new insights into the potential and limitations of DTI as a non-invasive structural MRI method for investigating tissue microstructure in brain diseases and disorders. Furthermore, the use of multiple imaging techniques like DTI, light microscopy, and SμXRD is a robust approach to evaluate tissue damage in pathological conditions. Therefore, the findings of this thesis highlight  the potential of using multimodal imaging approaches, which can be  translated into clinical applications.

How can the results of your doctoral research be utilised in practice?

In clinical practice, the interpretation of MRI data presents challenges. However, by studying brain diseases experimentally, there is an opportunity to characterize the brain at the cellular and subcellular levels using light microscopy and ex vivo imaging techniques like scanning micro-X-ray diffraction to understand the tissue structure. By comparing and interpreting both MRI and tissue data, it becomes possible to improve the understanding and interpretation of MRI findings in clinical patients. This thesis incorporated DTI, light microscopy, and scanning micro-X-ray diffraction as imaging modalities to comprehensively assess tissue damage at multiple scales, offering a complete structural characterization of the tissue damage, and improve the diagnosis in patients with brain damage in the clinics.

What are the key research methods and materials used in your doctoral research?

This thesis employed various advanced methods to evaluate the tissue microstructure following brain damage experimentally. Study I focused on utilizing in vivo DTI to examine microstructural damage during the acute and subacute phases of mTBI. Advanced automated quantitative histological analyses were performed to extract tissue-derived metrics comparable to DTI, and correlations were established between DTI and histological parameters. In Study II, a statistical multivariate model was developed to extend the interpretation of in vivo DTI by incorporating multiple tissue histological parameters in an animal model of epilepsy. Predictive modeling was also employed to evaluate in vivo DTI performance in detecting histopathological tissue changes. In study III, I evaluated the potential of ex vivo DTI using a multiscale imaging approach, comparing it with light microscopy and SμXRD in the subacute phase of mTBI. The integration of multiple advanced imaging modalities in this thesis expands the possibilities for obtaining a comprehensive understanding of tissue damage and interpreting DTI imaging results in future research studies.

The doctoral dissertation of Isabel San Martin Molina, entitled A multiscale imaging approach to assess brain damage in rats, will be examined at the Faculty of Health Sciences. The Opponent in the public examination will be Assistant Professor Eduardo A. Garza-Villarreal of the National Autonomous University of Mexico, and the Custos will be Docent Alejandra Sierra López of the University of Eastern Finland.

Doctoral defence 


For further information, please contact:

Isabel San Martin Molina, MSc, isabelsa(a)