Verification of the Ex Vivo Thiel Embalmed Model for Liver Treatment with Magnetic Resonance-guided Focused Ultrasound (MRgFUS) before Clinical Practice
Liver treatment is technically demanding due to the breathing motion and the presence of the ribcage around it, and non-invasive options are desirable. Magnetic Resonance-guided Focused Ultrasound (MRgFUS) is a promising treatment option due to its non-invasive nature and due to the ability to perform MR Thermometry. Thermometry can provide real-time temperature feedback and temperature maps indicating the ablated area. Despite considerable research on liver treatment with MRgFUS, developing a repeatable, safe and efficient ex vivo liver model has not been achieved. The Thiel embalmed model is more favourable than the fresh or formalin-fixed cadavers, due to its long-lasting, tissue-mimicking properties, and limited health risks. This thesis verified the Thiel embalmed liver, as a model for MRgFUS treatment before clinical practice, by using explanted organs and whole cadavers. The first set of experiments involved the measurement of acoustic parameters of Thiel embalmed tissue, and the scrutiny on the temperature response of the embalmed liver on FUS heating. Secondly, baseline phase-referenced Proton Resonance Frequency (PRF) MR Thermometry method was applied on Thiel liver to measure its thermal property (PRF coefficient). By this, the accurate temperature monitoring can be achieved on Thiel tissue. Thirdly, it was examined if the Thiel model is suitable to perform of reference-less PRF Thermometry during MRgFUS sonication. Fourthly, the MRgFUS sonication was performed on explanted liver and on whole human cadaver, in real-patient conditions. These conditions involved vascular visualization (with contrast agent), perfusion, respiratory motion, MR imaging and FUS heating under real-time temperature mapping. The results demonstrate that the acoustic parameters of the Thiel embalmed liver were different from the fresh liver, meaning that more acoustic power needs to be delivered to the target, to achieve ablative levels. Additionally, embalming with Thiel solution affected the temperature response, and resulted in different PRF coefficient. However, by using the measured coefficient, accurate thermometry can be performed with MRgFUS. Testing reference-less Thermometry algorithms was found suitable in a whole cadaver, with similarity between the reference-less algorithm temperatures and the actual temperatures. Vascular visualization with contrast agent was achieved in the explanted liver, and the cadaver proved feasible for respiration, vessel visualization and MRgFUS heating. Thus, the Thiel embalmed ex vivo model is favourable for MRgFUS treatment, in life-like conditions, before clinical practice. Additional spinous work suggested that the maximum temperatures achieved in the vertebrae and the intervertebral discs could achieve coagulative necrosis. The technologies and the research described in this thesis have been shown to overcome many of the present limitation and should therefore be useful for ongoing pre-clinical research on MRgFUS for liver treatment. Nevertheless, it is acknowledged that many crucial issues remain to be solved. These include repeatability studies to scrutinize if the PRF coefficient would change over a wider population of samples, investigation on magnetic susceptibility during measurement of the coefficient, and the combination of the real-time treatment of the liver, during respiratory motion and reference-less temperature mapping in a fully functional human cadaver. This thesis provided the fundamental starting point for testing different process parameters, such as real-time thermometry, FUS beam steering and tracking of the tumour location by using Thiel embalmed human cadavers.
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