Superparamagnetic iron oxide nanoparticle enhanced percutaneous microwave ablation: Ex-vivo characterization using magnetic resonance thermometry.

Abstract

Percutaneous microwave ablation (pMWA) is a minimally invasive procedure that uses a microwave antenna placed at the tip of a needle to induce lethal tissue heating. It can treat cancer and other diseases with lower morbidity than conventional surgery, but one major limitation is the lack of control over the heating region around the ablation needle. Superparamagnetic iron oxide nanoparticles have the potential to enhance and control pMWA heating due to their ability to absorb microwave energy and their ease of local delivery. The purpose of this study is to experimentally quantify the capabilities of FDA-approved superparamagnetic iron oxide Feraheme nanoparticles (FHNPs) to enhance and control pMWA heating. This study aims to determine the effectiveness of locally injected FHNPs in increasing the maximum temperature during pMWA and to investigate the ability of FHNPs to create a controlled ablation zone around the pMWA needle. PMWA was performed using a clinical ablation system at 915MHz in ex-vivo porcine liver tissues. Prior to ablation, 50uL 5mg/mL FHNP injections were made on one side of the pMWA needle via a 23-gauge needle. Local temperatures at the FHNP injection site were directly compared to equidistant control sites without FHNP. First, temperatures were compared using directly inserted thermocouples. Next, temperatures were measured non-invasively using magnetic resonance thermometry (MRT), which enabled comprehensive four-dimensional (volumetric and temporal) assessment of heating effects relative to nanoparticle distribution, which was quantified using dual-echo ultrashort echo time (UTE) subtraction MR imaging. Maximum heating within FHNP-exposed tissues versus control tissues were compared at multiple pMWA energy delivery settings. The ability to generate a controlled asymmetric ablation zone using multiple FHNP injections was also tested. Finally, intra-procedural MRT-derived heat maps were correlated with gold standard gross pathology using Dice similarity analysis. Maximum temperatures at the FHNP injection site were significantly higher than control (without FHNP) sites when measured using direct thermocouples (93.1±6.0°C vs. 57.2±8.1°C, p=0.002) and using non-invasive MRT (115.6±13.4°C vs. 49.0±10.6°C, p=0.02). Temperature difference between FHNP-exposed and control sites correlated with total energy deposition: 66.6±17.6°C, 58.1±8.5°C, and 20.8±9.2°C at high (17.5±2.2kJ), medium (13.6±1.8kJ), and low (8.8±1.1kJ) energies, respectively (all pairwise p<0.05). Each FHNP injection resulted in a nanoparticle distribution within 0.9±0.2cm radially of the injection site and a local lethal heating zone confined to within 1.1±0.4cm radially of the injection epicenter. Multiple injections enabled a controllable, asymmetric ablation zone to be generated around the ablation needle, with maximal ablation radius on the FHNP injection side of 1.6±0.2cm compared to 0.7±0.2cm on the non-FHNP side (p=0.02). MRT intra-procedural predicted ablation zone correlated strongly with post procedure gold-standard gross pathology assessment (Dice similarity 0.9). Locally injected FHNPs significantly enhanced pMWA heating in liver tissues, and were able to control the ablation zone shape around a pMWA needle. MRI and MRT allowed volumetric real-time visualization of both FHNP distribution and FHNP-enhanced pMWA heating that was useful for intra-procedural monitoring. This work strongly supports further development of a FHNP-enhanced pMWA paradigm; as all individual components of this approach are approved for patient use, there is low barrier for clinical translation.