背景:经皮微波消融(pMWA)是一种微创手术,该手术使用放置在针尖的微波天线来诱导致命的组织加热。它可以治疗癌症和其他疾病,发病率低于传统手术,但一个主要的限制是缺乏对消融针周围的加热区域的控制。超顺磁性氧化铁纳米颗粒具有增强和控制pMWA加热的潜力,这归因于它们吸收微波能量的能力以及它们易于局部递送。
目的:这项研究的目的是通过实验量化FDA批准的超顺磁性氧化铁铁血红素纳米颗粒(FHNP)增强和控制pMWA加热的能力。本研究旨在确定局部注射FHNP在pMWA期间提高最高温度的有效性,并研究FHNP在pMWA针头周围创建受控消融区的能力。
方法:使用915MHz的临床消融系统在离体猪肝组织中进行PMWA。消融前,通过23号针在pMWA针的一侧进行50uL5mg/mLFHNP注射。将FHNP注射部位的局部温度与无FHNP的等距对照部位直接比较。首先,使用直接插入的热电偶比较温度。接下来,使用磁共振测温法(MRT)无创测量温度,这使得能够对相对于纳米颗粒分布的热效应进行全面的四维(体积和时间)评估,使用双回波超短回波时间(UTE)减法MR成像进行量化。在多个pMWA能量递送设置下比较FHNP暴露的组织与对照组织内的最大加热。还测试了使用多次FHNP注射产生受控非对称消融区的能力。最后,使用Dice相似性分析,将术中MRT衍生的热图与金标准大体病理相关联.
结果:使用直接热电偶测量时,FHNP注射部位的最高温度显着高于对照(无FHNP)部位(93.1±6.0°C与57.2±8.1°C,p=0.002),并使用非侵入性MRT(115.6±13.4°C与49.0±10.6°C,p=0.02)。与总能量沉积相关的FHNP暴露位点和对照位点之间的温差:66.6±17.6°C,58.1±8.5°C,和20.8±9.2°C(17.5±2.2kJ),介质(13.6±1.8kJ),和低(8.8±1.1kJ)能量,分别(所有成对p<0.05)。每次FHNP注射导致纳米颗粒分布在注射部位径向0.9±0.2cm内,局部致死加热区限制在注射中心径向1.1±0.4cm内。多次注射启用了可控的,在消融针周围产生的非对称消融区,FHNP注射侧的最大消融半径为1.6±0.2cm,而非FHNP侧的最大消融半径为0.7±0.2cm(p=0.02)。MRT术中预测消融区与术后金标准大体病理评估密切相关(Dice相似性0.9)。
结论:局部注射FHNP可显著增强肝组织中的pMWA加热,并且能够控制pMWA针周围的消融区形状。MRI和MRT允许FHNP分布和FHNP增强的pMWA加热的体积实时可视化,这对于术中监测很有用。这项工作有力地支持了FHNP增强的pMWA范例的进一步发展;因为该方法的所有单个组件都被批准用于患者使用,临床翻译的障碍很低。
BACKGROUND: 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.
OBJECTIVE: 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.
METHODS: PMWA was performed using a clinical ablation system at 915 MHz in ex-vivo porcine liver tissues. Prior to ablation, 50 uL 5 mg/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.
RESULTS: 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 ± 2.2 kJ), medium (13.6 ± 1.8 kJ), and low (8.8 ± 1.1 kJ) energies, respectively (all pairwise p < 0.05). Each FHNP injection resulted in a nanoparticle distribution within 0.9 ± 0.2 cm radially of the injection site and a local lethal heating zone confined to within 1.1 ± 0.4 cm 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 ± 0.2 cm compared to 0.7 ± 0.2 cm 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).
CONCLUSIONS: 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.