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Dynamic and multi-nuclear magnetic resonance imaging for the assessment of nutrient and drug delivery in the human gastrointestinal tract

Final Report Summary - GI-MRI (Dynamic and multi-nuclear magnetic resonance imaging for the assessment of nutrient and drug delivery in the human gastrointestinal tract)

Gastrointestinal (GI) mechanisms for the transport of luminal contents through the stomach and small intestine have a decisive influence on the effectiveness of nutrient digestion and also medication. In patient groups, such as in patients suffering from diabetes, physiological variables describing the GI transport - such as GI transit time - may vary considerably from normal values. Therefore, it is urgently necessary to determine gastrointestinal transport mechanisms by means of fitting robust methods. To date, standard methods such as endoscopy or manometry do not provide such means. In recent years, it has been shown that magnetic resonance imaging (MRI) is valuable for determining a number of GI functions. Compared with other imaging modalities such as computed tomography (CT) or positron emission tomography (PET), MRI is characterised among other things by a high degree of flexibility with regard to the achieved image contrast, a very high soft tissue contrast and the absence of harmful ionising radiation. Therefore, there is hope that MRI could also be used for the determination of GI transport mechanisms. However, keeping track of GI content by standard clinical MRI is challenging due to constant peristaltic movement, a complex three-dimensional (3D) arrangement of the small intestine and a generally low contrast in the gastrointestinal area. Clinical Imaging is usually determined by the hydrogen nucleus (1H). Water and fat are examples of structures which can be visualised and distinguished by 1H MRI. However, MRI in the same way allows imaging of structures that do not contain 1H nuclei, e.g. imaging of perfluorocarbons containing only carbon and the fluorine nuclide 19-fluorine (19F). Exogenously administered 19F based substances can be visualised and their 3D position in the human body can be tracked over a long period of time due to the essentially zero abundance of 19F in the human body. The present work describes methods which use 19F MR imaging in conjunction with exogenously introduced 19F substances to investigate transport mechanisms in the human small intestine and to obtain spatial and temporal control over tools that are introduced into the human body for diagnostic or interventional purposes.

In an initial proof-of-principle study, we demonstrated the measurement of intestinal transit and motor function by means of 19F labelled capsules that were orally administered and tracked inside the human gastrointestinal (GI) tract by rapid 19F MRI. The acquired 3D data made it also possible to carry out a 3D reconstruction of the complex geometry of the small intestine. An additional study showed that unique capsule identification is possible by using different 19F solutions of different 19F resonance frequencies. The 19F capsules used in this first study were further optimised in a second step for future large-scale human application. Three different capsule types with two different 19F solutions were systematically tested for bio-compatibility and leakage using statistical analysis. One capsule type was selected for the in vivo experiments.

The developed 19F MRI methodology for the tracking of point-like objects in the human abdomen was enhanced in order to simultaneously track a greater number of administered 19F capsules. Three identical 19F capsules in the small intestine and four identical capsules placed along a gastroduodenal catheter could be simultaneously traced in the gastro-oesophageal region. To make this possible, a special MRI sequence was used which is based on a 3D extension of the so-called golden means and shows advantageous properties in many respects. Using this sequence, it was e.g. possible to develop an image reconstruction algorithm, which allowed adjustments to the chosen temporal resolution even after the completion of the image data acquisition. This property was used to determine the optimal temporal resolution for the tracking of gastroduodenal catheters that were labelled with 19F capsules (multi-point 19F gastroduodenal catheter). Three different algorithms for localisation of capsule positions were developed and compared. It was found that appropriate prior knowledge of the geometry of the tracked object - in this particular case, prior knowledge of the geometry of a gastroduodenal catheter - leads to a reduced number of falsely identified capsule positions. The results of the study showed that a stable tracking of the developed multi-point gastroduodenal catheter is possible and that the described methodology can also be used for the tracking of multiple independent small capsules in physiological studies.

The developed method for the tracking of multi-point catheters was used in an additional study to calculate in real-time parameters for 1H imaging, which is carried out along the catheter position. Such 19F based 1H imaging can be applied for example in the area of the oesophagus, where fast dynamic 1H imaging can be performed order along the 3D position of a nasally inserted catheter for the visualisation of swallowing or reflux events. The calculation of the catheter position was carried out on an external computer, which was fed in real-time with data from the MRI machine. It was shown that it is possible to visualise and project information on the position and velocity of the catheter in the MRI scan room with minimal latency.

Finally, in a pilot study on 15 healthy volunteers that received two differently 19F labelled capsules on two study days was performed. One capsule was labelled with perfluoro-15-crown-5-ether ether (PCE) and the other capsule with hexafluorobenzene (HFB). The two capsules were swallowed simultaneously and their passage through the small intestine was tracked. The performance of the two liquids was compared with respect to signal gain and first physiological parameters were calculated. It was shown that PCE signal gain was about 25 % higher than for HFB. The 3D geometries of the small intestine reconstructed from the positions of the two capsules showed a good agreement. The pilot measurements also showed a similar behaviour of the two capsules with respect to their velocities.

The methods developed in this work show the potential of 19F MR imaging in humans. Possible application areas for the developed methods are mainly physiological and pharmacological studies, as well as the clinical use. For physiological studies, the quantification of transit time, local motor activity and segmentation of small intestinal contents as well as the analysis of the intestinal 3D structure are most relevant. In pharmacological studies, statements about transport and dissolving processes can be made by integrating 19F capsules into conventional medical capsules or tablets. Finally, clinical diagnosis of functional gastrointestinal disorders can be supplemented by the developed methods, and gastroduodenal devices such as endoscopes can be tracked in clinical applications.

For further details and images on the 19F MRI project, please contact Dr Andreas Steingoetter at the Division of Gastroenterology ad Hepatology, University Zurich. Email: andreas.steingoetter@uzh.ch

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