Electromagnetic modelling and experimentation for the development of a novel microwave thermal ablation therapy for adrenal tumours

Primary Aldosteronism is the main cause of the secondary hypertension, due to the abnormal functioning of the adrenal glands. Adreno-cortical adenomas and bilateral hyperplasia are the most common causes of the abnormal release of the hormone regulating the blood pressure in the adrenal glands. Eradicating the tumours and restoring the normal activity of the adrenal gland is crucial to address this condition. To date, surgical removal of the gland and pharmacotherapy are the gold standard techniques adopted in the management of unilateral adenomas and bilateral hyperplasia, respectively. Both techniques present drawbacks linked to invasiveness and ineffectiveness. Currently, alternative techniques to the standard therapies are under investigation for the treatment of adrenal neoplasms. Recent clinical studies showed promising results in adopting thermal ablation techniques to eradicate solitary and encapsulated adrenal adenomas, and restore normal values of blood pressure and blood-hormone concentrations. However, most of the functional adrenal anomalies arise from the external part of the adrenal cortex and are covered by a fat layer enveloping the adrenal gland. In all these cases, the conventional approach to pierce the tumour and induce extremely high or low temperatures may increase the risk to compound the entire gland and the surrounding structures, with detrimental effects on the outcomes of the procedure. In this thesis, the use of microwave thermal ablation is studied for the selective removal of shallow adenomas. In particular, a ‘side firing’ approach is proposed. This new approach relies on the intrinsic anatomical and dielectric characteristics of the adrenal gland and its surrounding fat capsule. More specifically, this thesis explores the possibility of using the fat layer enveloping the adrenal gland as a tool to selectively direct the electromagnetic energy into the tumour and shield the surrounding tissues. Firstly, an animal model is chosen to study the dielectric properties of the adrenal gland. Next, the dielectric properties of ex vivo human adrenal tissues, both healthy and diseased, are measured and compared with those of the animal model. The dielectric properties of the target tissues are characterised at the operational frequencies typically adopted for microwave thermal ablation. The degree of dielectric contrast with fat tissue is assessed. This contrast supports the proposed ‘side firing’ approach. Secondly, a proof-of-concept study is completed to investigate the effect of the fat layer on the distribution of the electromagnetic energy and temperature in a simplified scenario. A microwave applicator operating at 2.45 GHz is placed at the interface between a muscle and fat layer. The outcomes show that the fat acts as a natural shield, helping to focus the electromagnetic energy toward a preferential direction. The fat-muscle interface is adopted in this preliminary study due to the conservative degree of dielectric contrast existing between muscle and fat compared to the contrast between the adrenal tissues and fat. Also, the large availability both of muscle and fat has facilitated the experimental assessment of the numerical study. Given the positive results of the proof-of-concept study, the same ‘side firing’ approach at the same operating frequency (2.45 GHz) is applied using planar and 3D adrenal models representing the adrenal gland and its fat capsule. The effect of different geometrical characteristics of the target and different orientations of the microwave applicator on the shielding effect of the fat layer is studied numerically. Two levels of energy are considered both for ex vivo and in vivo conditions. Ex vivo and in vivo experimental microwave ablation procedures validate the proposed ‘side firing’ approach. Histology analyses of the ex vivo and in vivo samples confirmed the capability of the fat layer to induce asymmetric ablations and protect the surrounding sensitive structures (i.e. blood vessel). Lastly, a higher MWA operating frequency, 5.8 GHz, is investigated. The higher dielectric contrast observed at higher frequencies compared with 2.45 GHz, suggests that a more focused ‘side firing’ effect is achievable. The shielding effect of the fat layer is confirmed also at 5.8 GHz. Moreover, the increase of the contrast in the electrical conductivity between the fat layer and the adrenal tissue helps to improve the thermal coverage and the sphericity of the ablation zone in the tissue target. In summary, this thesis provides a comprehensive understanding of the role of the fat enveloping the tissue target during microwave ablation procedures and the possibility of using this anatomical characteristic to create directional ablation zones. The results included in this thesis may provide additional information to improve the clinical protocols for the treatment of adreno-cortical adenomas through microwave thermal ablation.2022-09-2