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Triple Imaging with PARASHIFT Probes

Lead Research Organisation: Newcastle University
Department Name: Translational and Clinical Res Institute

Abstract

Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.
 
Description We investigated the use of specific types of metals (lanthanide metals) placed at the core of larger molecules which could be used a contrast agents to enhance the information obtained from magnetic resonance imaging (MRI) scans. Contrast agents are in common use in MRI and normally work by an indirect detection method whereby the presence of the agent changes the strong MRI signal which comes from water in the tissue. The new part of this work is that we directly detect the contrast agent itself. The properties of this directly detected signal vary with factors such as the tissue acidity (pH) and temperature. We are able to then use the signals to measure the local pH and temperature in the tissue, which are important factors when assessing pathological tissue.

We developed new MRI scanning sequences in combination with selecting different metal used in the core of the contrast molecule. We specifically worked with the metals Dysprosium, Terbium, Thulium and Erbium. The signals are extremely weak due to the low concentration of contrast agent which can be injected into living tissue and the agents are quickly removed from the tissue in the blood and excreted, making them very transient (lasting only 10-15 minutes). Although weak, the signals were easily detectable.

We encountered significant challenges in making precise quantification of the pH from the signals due to interference from the large MRI signal arising from water. These challenges were partly overcome using new MRI scanning methods, but remained the limiting factor in further development of this type of approach.
Exploitation Route The work conducted by our partners at Durham University (chemistry expertise and molecule synthesis) also revealed new fundamental understanding of NMR signal behaviour.

The concept of responsive contrast agents based on lanthanide metal cores has been demonstrated and remains an interesting approach. The sensitivity threshold for detection needs to be improved by increasing the residence time in tissue to provide sufficient time for robust data collection.
Sectors Healthcare
 
Description The work conducted has opened up new avenues of investigation and has been taken up internationally and nationally (S Falkner, Oxford). We are no longer able to pursue this avenue as the PI (Parker, Durham) has retired in 2021 and the co-I (Blamire, Newcastle) was unable to continue in the field due to instrument failure.
First Year Of Impact 2021
Sector Healthcare
Impact Types Cultural

Economic
 
Title Data from: Assessment of disease progression in dysferlinopathy - a one year cohort study 
Description Objective: To assess the ability of functional measures to detect disease progression in dysferlinopathy over 6 months and 1 year. Methods: 193 patients with dysferlinopathy were recruited to the Jain Foundation's International Clinical Outcome Study for Dysferlinopathy. Baseline, 6 months and 1 year assessments included: adapted North Star Assessment (a-NSAA), Motor Function Measure (MFM-20), timed function tests, 6 minute walk test (6MWT), Brooke Scale, Jebsen Test, manual muscle testing (MMT) and hand-held dynamometry (HHD). Patients also completed the ACTIVLIM questionnaire. Change in each measure over 6 months and 1 year was calculated and compared between disease severity (ambulant (mild, moderate or severe based on a-NSAA score) or non-ambulant (unable to complete a 10m walk)) and clinical diagnosis. Results: The functional a-NSAA test was the most sensitive to deterioration for ambulant patients overall. The a-NSAA score was the most sensitive test in the mild and moderate group while 6MWT was most sensitive in the severe group. The 10m walk test was the only test showing significant change across all ambulant severity groups. In non-ambulant patients, the MFM domain 3, wrist flexion strength and pinch grip were most sensitive. Progression rates did not differ by clinical diagnosis. Power calculations determined that 46 moderately affected patients are required to determine clinical effectiveness for a hypothetical 1 year clinical trial based on the a-NSAA as a clinical endpoint. Conclusion: Certain functional outcome measures can detect changes over 6 months and one year in dysferlinopathy and potentially be useful in monitoring progression in clinical trials. 
Type Of Material Database/Collection of data 
Year Produced 2019 
Provided To Others? Yes  
URL https://datadryad.org/stash/dataset/doi:10.5061/dryad.tp08m60