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Development and evaluation of ingestible microbubble-based contrast agents for meal pressure MRI within the human stomach

Abdurakman, E. ORCID: 0000-0002-7043-052X (2019). Development and evaluation of ingestible microbubble-based contrast agents for meal pressure MRI within the human stomach. (Unpublished Doctoral thesis, Nottingham Trent University)

Abstract

Gas-filled microbubbles suspended in a liquid or suitable gel are useful as a pressure probe for MRI. These microbubbles create size-dependent magnetic perturbation in their immediate vicinity, which alters the measured MR signal. The flexibility of these biocompatible bubbles enables them to undergo a change in size due to a change in pressure, resulting in a measurable MR signal change. The novel work we present here focuses on demonstrating, by in-vitro and in-vivo investigations, that phospholipid microbubbles entrapped in alginate spheres can be used as a contrast agent to measure pressure variations in the human stomach. The development of the pressure-sensitive contrast agent by entrapping microbubbles into alginate gel spheres is first presented. The T2eff relaxation time of the alginate spheres has been assessed using an MSME sequence and is found to decrease by a factor of 2 in the presence of microbubbles. Furthermore, by applying increasing pressure on to the alginate spheres containing microbubbles, the T2eff is seen to increase as the pressure increases, with a sensitivity of 43% change per bar. The pressure sensitivity of the contrast agent is further assessed, in-vitro, by performing rapid pressure cycle experiments with the use of the RARE sequence, which exhibited around 40% signal change per bar, in both the 2.35T small animal Bruker and the 3T whole body Philips MRI scanners. Although this sensitivity is seen to decrease in the presence of a simulated gastric acid solution, the effect has been minimised by suspending the alginate spheres in a locust bean gum gel with a 2% w/v concentration. The gel solution is also acting as an immobiliser tool preventing the spheres from rising due to the buoyancy of the microbubbles. The capability of the contrast agent in sensing the dynamic pressure change in the stomach is then tested through in-vivo investigation. The study has been carried out on healthy human volunteers by preparing contrast agent as a meal for direct ingestion and v further imaged with the 3T whole body scanner. Initial results with the RARE sequence showed the signal change was dominated by the breathing movement, an artefact which was then dramatically reduced by the use of the BTFE sequence. However, the heterogeneity of the meal being captured in different images of the dynamic measurement was found to be another contributing artefact and we attempted to minimise this by locking the image acquisition to a specific volume of the meal with the use of respiratory triggering. As a result, the signal intensity change exhibited in the meal within the antrum region is between 5 to 10%. This is slightly higher than expected signal variation which should be around 1.6 to 4.3%, when considering the typical 40% per bar sensitivity. Nevertheless, a novel pressure-sensitive contrast agent has been produced and its capability in measuring pressure changes in simulated human gastric conditions has been demonstrated. Furthermore, the preliminary in-vivo study demonstrates that this contrast agent shows great potential in sensing the dynamic pressure change in the human stomach. As a medical diagnostic tool, this will be useful for the clinician as an alternative avenue from the current invasive methods in diagnosing the clinical conditions related to functional dyspepsia.

Publication Type: Thesis (Doctoral)
Additional Information: This work is the intellectual property of the author. You may copy up to 5% of this work for private study, or personal, non-commercial research. Any re-use of the information contained within this document should be fully referenced, quoting the author, title, university, degree level and pagination. Queries or requests for any other use, or if a more substantial copy is required, should be directed to the owner(s) of the Intellectual Property Rights.
Subjects: R Medicine
Departments: School of Health Sciences > Midwifery & Radiography
URI: http://openaccess.city.ac.uk/id/eprint/22798
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