Periodic Reporting for period 4 - DiSCo MRI SFN (Developing Integrated Susceptibility and Conductivity MRI for Next Generation Structural and Functional Neuroimaging)
Reporting period: 2023-10-01 to 2024-09-30
MRI is indispensable in the diagnosis of neurodegenerative diseases. These are poorly understood while their prevalence and socio-economic burden continue to rise. Structural and functional MRI can provide biomarkers for early diagnosis and potential therapeutic intervention. My research vision is to develop novel MRI methods for structural and functional mapping of tissue magnetic susceptibility and electrical conductivity as these show great promise for neuroimaging in diseases such as Alzheimer’s (AD).
Susceptibility mapping (SM), which I pioneered, is uniquely sensitive to tissue composition including iron content affected in AD while conductivity mapping (CM) may reflect cellular disruption in AD. Resting-state functional MRI (rsfMRI) reveals how AD affects brain networks without any tasks or stimulation equipment. However, each technique currently needs a separate time-consuming MRI scan. I will develop an integrated scan for simultaneous structural SM and CM, and rsfMRI functional connectivity characterisation. This efficient scan, ideal for AD patients, will reveal new resting-state networks based on electromagnetic properties: resting-state functional SM (rsfSM) and resting-state functional CM for the first time. As changes in blood susceptibility underlie conventional fMRI, rsfSM should measure functional connectivity more directly. This also makes it sensitive to physiological noise so I will develop noise removal methods building on fMRI techniques I established. Initial fSM studies have been at 7 Tesla but I will target the more widespread 3T field to maximise applicability. As a leader in both SM and rsfMRI physiological noise removal, I have the ideal background to integrate SM and CM with fMRI and extend them for ground-breaking functional electromagnetic connectivity. This research will yield a rich set of novel, multimodal MRI contrasts to allow development of new combined structural and functional biomarkers for early diagnosis of AD and other diseases.
Susceptibility mapping (SM), which I pioneered, is uniquely sensitive to tissue composition including iron content affected in AD while conductivity mapping (CM) may reflect cellular disruption in AD. Resting-state functional MRI (rsfMRI) reveals how AD affects brain networks without any tasks or stimulation equipment. However, each technique currently needs a separate time-consuming MRI scan. I will develop an integrated scan for simultaneous structural SM and CM, and rsfMRI functional connectivity characterisation. This efficient scan, ideal for AD patients, will reveal new resting-state networks based on electromagnetic properties: resting-state functional SM (rsfSM) and resting-state functional CM for the first time. As changes in blood susceptibility underlie conventional fMRI, rsfSM should measure functional connectivity more directly. This also makes it sensitive to physiological noise so I will develop noise removal methods building on fMRI techniques I established. Initial fSM studies have been at 7 Tesla but I will target the more widespread 3T field to maximise applicability. As a leader in both SM and rsfMRI physiological noise removal, I have the ideal background to integrate SM and CM with fMRI and extend them for ground-breaking functional electromagnetic connectivity. This research will yield a rich set of novel, multimodal MRI contrasts to allow development of new combined structural and functional biomarkers for early diagnosis of AD and other diseases.
We have made advances in conductivity mapping (CM) techniques: New Approaches for Phase-based Quantitative Conductivity Mapping in Noisy Images (A Karsa, U Katscher, B Bachrata, B Dymerska, S Robinson, K Shmueli) presented at the 2021 annual meeting of the International Society for Magnetic Resonance in Medicine (ISMRM). Dr Karsa’s software implementation of these methods (https://xip.uclb.com/product/MRI_conductivity(opens in new window)) has been downloaded several times despite the small international CM community.
We have developed methods to improve susceptibility mapping (SM) including a new phase unwrapping technique and a tilted acquisiton correction technique:
B Dymerska, K Eckstein, B Bachrata, B Siow, S Trattnig, K Shmueli, SD Robinson (2020). Phase unwrapping with a rapid open source minimum spanning tree algorithm (ROMEO). Magn Reson Med, https://doi.org/10.1002/mrm.28563(opens in new window) highlighted here: https://blog.ismrm.org/2021/03/26/reproducible-research-insights-with-barbara-dymerska-korbinian-eckstein-and-simon-robinson/(opens in new window).
O Kiersnowski, A Karsa, S Wastling, J Thornton, K Shmueli. The Effect of Oblique Image Acquisition on the Accuracy of Quantitative Susceptibility Mapping and a Robust Tilt Correction Method https://doi.org/10.1101/2021.11.30.470544(opens in new window).
To achieve our aims, we plan to use an echo-planar imaging (EPI) sequence with Simultaneous Multi-Slice Acceleration and have shown that this has no effect on SM quality and accuracy. This work will be presented at the 2022 ISMRM: O Kiersnowski, P Fuchs, S Wastling, J Thornton, K Shmueli. Simultaneous Multi-Slice Acceleration of Multi-Echo EPI Provides Rapid and Accurate QSM.
We have participated in several inter-disciplinary collaborations, applying some of the SM techniques we have developed to gain insights into different brain diseases and pathologies. For example, our SM techniques, correlated with gene transcription maps have provided new insights into neurodegeneration in Parkinson’s disease i.e. we identified the profile of gene transcription in the healthy brain that underlies increased cortical magnetic susceptibility values in PD patients relative to controls. See, Thomas GEC, Zarkali A, Ryten M, Shmueli K, Gil-Martinez AL, Leyland LA, McColgan P, Acosta-Cabronero J, Lees AJ, Weil RS. Regional brain iron and gene expression provide insights into neurodegeneration in Parkinson's disease. Brain. 2021 Jul 28; 144(6):1787-1798. https://doi.org/10.1093/brain/awab084(opens in new window).
We have developed methods to improve susceptibility mapping (SM) including a new phase unwrapping technique and a tilted acquisiton correction technique:
B Dymerska, K Eckstein, B Bachrata, B Siow, S Trattnig, K Shmueli, SD Robinson (2020). Phase unwrapping with a rapid open source minimum spanning tree algorithm (ROMEO). Magn Reson Med, https://doi.org/10.1002/mrm.28563(opens in new window) highlighted here: https://blog.ismrm.org/2021/03/26/reproducible-research-insights-with-barbara-dymerska-korbinian-eckstein-and-simon-robinson/(opens in new window).
O Kiersnowski, A Karsa, S Wastling, J Thornton, K Shmueli. The Effect of Oblique Image Acquisition on the Accuracy of Quantitative Susceptibility Mapping and a Robust Tilt Correction Method https://doi.org/10.1101/2021.11.30.470544(opens in new window).
To achieve our aims, we plan to use an echo-planar imaging (EPI) sequence with Simultaneous Multi-Slice Acceleration and have shown that this has no effect on SM quality and accuracy. This work will be presented at the 2022 ISMRM: O Kiersnowski, P Fuchs, S Wastling, J Thornton, K Shmueli. Simultaneous Multi-Slice Acceleration of Multi-Echo EPI Provides Rapid and Accurate QSM.
We have participated in several inter-disciplinary collaborations, applying some of the SM techniques we have developed to gain insights into different brain diseases and pathologies. For example, our SM techniques, correlated with gene transcription maps have provided new insights into neurodegeneration in Parkinson’s disease i.e. we identified the profile of gene transcription in the healthy brain that underlies increased cortical magnetic susceptibility values in PD patients relative to controls. See, Thomas GEC, Zarkali A, Ryten M, Shmueli K, Gil-Martinez AL, Leyland LA, McColgan P, Acosta-Cabronero J, Lees AJ, Weil RS. Regional brain iron and gene expression provide insights into neurodegeneration in Parkinson's disease. Brain. 2021 Jul 28; 144(6):1787-1798. https://doi.org/10.1093/brain/awab084(opens in new window).