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MRI Signal To Recover Unique Cerebral TissUe Response to changEs

Periodic Reporting for period 1 - MRI-STRUCTURE (MRI Signal To Recover Unique Cerebral TissUe Response to changEs)

Reporting period: 2018-04-01 to 2020-03-31

While several pathologies can affect the brain over the lifespan, all involving different kind of microstructural changes affecting specific tissue compartments like myelin, axons, glia cells or neurons, our ability to diagnose and monitor disease progression, as well as evaluate the efficacy of new therapies, is limited by the lack of specificity of current non-invasive imaging techniques. In other words, current diagnostic tools for looking at brain structure and function can tell us that there is a damage, but often they are not capable of telling us exactly which compartment is damaged. An instrument capable of increasing the specificity of our analysis when looking into the brain is expected to have a tremendous impact on how brain diseases are diagnosed and treated, with a huge benefit for our society. As a matter of fact, the proportion of the global burden of disease that is attributable to neurological, mental health, developmental and substance-use disorders, which is already really high, is expected to rise further in the near future due to the increase in life expectation.
The project MRI-STRUCTURE (Magnetic Resonance Imaging Signal To Recover Unique Cerebral TissUe Response to changEs) aims at developing an innovative imaging technique, based on magnetic resonance, to look at different cell compartments in the brain, in vivo and non-invasively. To develop this framework, I took advantage of the possibility of decomposing the magnetic resonance signal measured in the brain into the contributions of the different cellular compartments. To validate it, I have used the rodent brain to induce a controlled tissue response similar to the reaction observed in different brain pathologies (inflammation, myelin and axonal damage). I then measured the change in the MRI images and compared it with post-mortem histological results, demonstrating that the MRI signal contains the fingerprints of specific cellular compartments, and that these contributions can be teased apart. As a proof of concept of the utility of MRI-STRUCTURE in clinics, I have adapted the imaging protocol to a human scanner to demonstrate the feasibility of the approach. To facilitate even further the adoption of advanced magnetic resonance imaging techniques in hospitals, I have worked with the startup QMENTA to make the analysis platform available in the cloud in a streamlined and easily accessible fashion. All in all, this innovative brain imaging approach is expected to impact on our ability to fight neurodegenerative and inflammatory diseases, by achieving early diagnosis, personalized monitoring of the disease progression and of the efficacy of new therapies.
MRI-STRUCTURE was planned in different steps, integrated with a multi-disciplinary vision.
The first step of the project was to develop a mathematical strategy to decompose the magnetic resonance signal coming from the brain and measured through an MRI scanner into the contributions of the different biological compartments which constitute the tissue. This is possible because the specific MRI acquisition used is sensitive to the displacement of water molecules within the different tissue compartments, and compartments with different shapes (like axons, glia, neurons) mold the signal in a different way. This part of the project has been possible due to the interaction between my background as a physicist specialized in water diffusion dynamics, and the host institution, the Institute of Neuroscience of Alicante, where I was able to find expertise in neurobiology and neuroanatomy.
The second important step was the validation of the framework. This was done by using rat brain as a model for human brain tissue, and generating through manipulations the tissue reactions most frequently associated to brain pathologies: inflammation, myelin and axonal damage. The rats were then scanned in the MRI, and after sacrifice they underwent more invasive procedures to verify the kind and extent of the damage. As such, it was possible to relate brain features measured with MRI in vivo and non-invasively to characteristics of the damaged brain that are so far only measurable postmortem.
The following step was to exploit the great adaptability of the advances developed in the animal MRI scanner to the human MRI scanner; to do so, I have adapted the framework to a human scanner, and acquired MRI of healthy volunteers, demonstrating that the same analysis which was validated in rats can also be performed in humans. This part of the project was realized in the Cardiff University Brain Imaging Centre in the UK, as a part of the first secondment.
The last phase of the project involved dissemination of the results. As a matter of facts, non-invasive diagnosis by advanced MRI has progressed a lot in recent years; however, the transfer of the new methodologies to the clinic remains difficult, and the clinical diagnosis in the daily practice of radiology services is still carried out with very basic means. Therefore, I have worked with the Barcelona-based startup QMENTA to make the analysis platform available in the cloud in a streamlined and easily accessible fashion, with the final aim of transferring the innovative MRI framework to clinical settings, so that it can have a real impact on the diagnosis and daily medical practice. This collaboration was possible thanks to the secondment in Barcelona.
To disseminate the results of the project to the lay public, I have also participated to other important initiatives: MRI-STRUCTURE was chosen by the European Research Council to be presented at the 2019 Science is wonderful! Event during the European research and innovation days in Brussels, with more than 5000 people attending. In addition, during the Spanish 2020 Brain Awareness Week, I have collaborated with the plastic artist Iñaqui Ortega Vidal to exhibit a sculpture inspired by microglia cells, one of the cellular compartments that can be seen and studied thanks to the results obtained by MRI-STRUCTURE.
"Current diagnostic tools for looking inside brain can tell us that there is a damage, but often they are not capable of telling us exactly which compartment is damaged. One cellular compartment which is receiving special attention in the last few years is the glial compartment, the collection of cells involved in the brain’s immune reaction to stimuli or inflammation. In fact, neuroinflammation has become a hot topic in brain research, due to its involvement in several neurodegenerative and psychiatric disorders: to cite only a few, Alzheimer’s and Parkinson’s diseases, multiple sclerosis, stroke, schizophrenia, addiction. If neuroinflammation is closely related to all these pathologies, by targeting the immune cells of the brain in the proper way, it could be possible to slow down the disease progression. Therefore, an instrument to look non-invasively at the status of the inflammatory system in the brain is expected to have a tremendous impact on how brain diseases are diagnosed and treated, with a huge benefit for our society. All in all, the results obtained in the context of this project meet the targets of the European Horizon 2020 programme (specifically: developing better diagnostics and more effective therapies to take care of the ageing population) and the United Nation Agenda 2030 signed by 193 countries worldwide (specifically: #3 Good health and well-being)."
MRI-STRUCTURE imaging framework to detect inflammation non-invasively