Periodic Reporting for period 2 - MS-fMRI-QSM (Studying Multiple Sclerosis with a novel simultaneous functional Magnetic Resonance Imaging (fMRI) and Quantitative Susceptibility Mapping (QSM) sequence.)
Okres sprawozdawczy: 2021-08-01 do 2022-07-31
Multiple sclerosis (MS) is the most common autoimmune disorder to affect the central nervous system. The body’s immune system attacks the myelin sheath surrounding nerve cells, slowing electrical signals and causing visual and sensorimotor deficits, cognitive decline and mood changes. Magnetic Resonance Imaging (MRI) plays a central role in the diagnosis of MS through the identification of plaques and active lesions, though MS can often only be definitively diagnosed when the number of lesions has been shown to increase over repeated examinations spanning months or years. Recently, functional MRI (fMRI) and Quantitative Susceptibility Mapping (QSM) have been shown to provide insights into the pathogenesis of MS and possible biomarkers of MS subtypes (relapsing-remitting (RR), primary progressive (PP) and secondary progressive (SP)). fMRI shows aberrant neuronal activation in response to motor tasks and changes to the motor resting state networks which are different in RR, PP and SP MS, for instance, whereas QSM provides images of the magnetic susceptibilities of different tissues, revealing iron deposits and demyelination.
A central objective of this project was the development of a new MRI method which allows functional (fMRI) and structural (QSM) data to be acquired simultaneously rather than in two separate scans. This drastically reduces the scan time. In the second stage of the project, the combined fMRI-QSM sequence has been used to examine, in different MS subtypes, reorganization of motor function and disruption of functional connectivity (from fMRI) in relation to the distribution of plaques, iron and demyelination (from QSM). This promises to allow MS to be diagnosed at an earlier stage, so that patients can begin treatment before damage accumulates. These new imaging methods will contribute to extending the healthy life expectancy of patients and reducing the burden on carers and health and support services.
A central objective of this project was the development of a new MRI method which allows functional (fMRI) and structural (QSM) data to be acquired simultaneously rather than in two separate scans. This drastically reduces the scan time. In the second stage of the project, the combined fMRI-QSM sequence has been used to examine, in different MS subtypes, reorganization of motor function and disruption of functional connectivity (from fMRI) in relation to the distribution of plaques, iron and demyelination (from QSM). This promises to allow MS to be diagnosed at an earlier stage, so that patients can begin treatment before damage accumulates. These new imaging methods will contribute to extending the healthy life expectancy of patients and reducing the burden on carers and health and support services.
The applicant and researchers at the University of Queensland have developed the combined fMRI-QSM sequence, which takes advantage of phase information inherent in the images to correct for distortions which are the usual down-side of rapid methods (Robinson et al., 2021). The sequence was implemented in the MRI Image Reconstruction Environment, and has been tested in 27 subjects on the 3T MRI and 7T MRI scanners at the University of Queenslands’ Centre for Advanced Imaging. The distortion correction was implemented in MATLAB and distributed with the publication reporting that aspect. The imaging has involved the development of an entirely new ‘simultaneous multiple resonance frequency’ (SMURF) approach to fat-water imaging (Bachrata et al., 2021b), which will allow the fMRI-QSM sequence to be applied to fatty tissues around the neck and spinal cord, as well as cerebellum (Bachrata et al., 2021a). The processing of a large number of phase images arising from an fMRI measurement needs a fast and reliable method to remove an image artefact known as phase ‘wrap’ from the EPI. This has been developed (Dymerska et al., 2021) and distributed in open-source form (https://github.com/korbinian90/ROMEO). This has been integrated into the most popular meta-tool for QSM, SEPIA (https://sepia-documentation.readthedocs.io/en/latest/gui/Phase-unwrapping-standalone.html) and into a package for phase imaging which is being used by 34 ultra-high field (7T or higher field strength) MRI sites around the world - approximately one third of the global ultra-high field network. The fMRI-QSM was adapted for use in a clinical research setting at 3T and installed at the Neurology Department of the Medical University of Graz, where it has been used in a study of >70 patients. A further 30 patients have been studied with an additional super-fast scan which allows QSMs to be generated in approximately 10 seconds.
The combined fMRI-QSM sequence allows maps of brain function and the magnetic "susceptibility" of the brain (QSM) to be investigated simultaneously. This is much quicker than performing the fMRI and QSM scans separately. Because it is so fast, the measurement is also robust to patient motion. The results of the two measures are inherently coregistered to each other and – being free of distortion - easy to coregister to other scans, and of an unprecedented resolution compared to prior fMRI studies of Multiple Sclerosis. fMRI-QSM has the potential to identify disruption to motor and resting state network function and to correlate these with demyelination and iron accumulation in a single measurement. Assessing iron accumulation, demyelination and disruption to functional networks in different cohorts - patients with clinically isolated syndrome (CIS), relapsing-remitting MS (RRMS) without disability and RRMS with mild to moderate disability as well as healthy controls is anticipated to provide insight into structural-functional disruptions in different types of Multiple Sclerosis and into possible mechanisms of disease progression. The patient data acquired at the Neurology Department of the Medical University of Graz is under analysis. Initial findings are that most of the multiple sclerosis lesions which are visible using a conventional 5-10 minute MRI scan can be identified with the super-fast (12 seconds) QSM. An assessment of the functional data is underway. The hope is that these will provide candidate imaging biomarkers which will allow Multiple Sclerosis to be identified at an earlier stage and provide an effective means to monitor therapy, improving patient welfare and benefitting carers and society as a whole.