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

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. PURPOSE: 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.

Ocular Pulse Amplitude Correlates With Ocular Rigidity at Native IOP Despite the Variability in Intraocular Pulse Volume With Each Heartbeat.

Purpose: The purpose of this study was to assess ocular coat mechanical behavior using controlled ocular microvolumetric injections (MVI) of 15 µL of balanced salt solution (BSS) infused over 1 second into the anterior chamber (AC) via a syringe pump. Methods: Intraocular pressure (IOP) was continuously recorded at 200 Hz with a validated implantable IOP telemetry system in 7 eyes of 7 male rhesus macaques (nonhuman primates [NHPs]) during 5 MVIs in a series at native (3 trials), 15 and 20 mm Hg baseline IOPs, repeated in 2 to 5 sessions at least 2 weeks apart. Ocular rigidity coefficients (K) and ocular pulse volume (PV) were calculated for each trial. Data were averaged across sessions within eyes; PV was analyzed with a three-level nested ANOVA, and parameter relationships were analyzed with Pearson Correlation and linear regression. Results: After MVI at native baseline IOP of 10.4 ± 1.6 mm Hg, IOP increased by 9.1 ± 2.8 mm Hg (∆IOP) at a 9.6 ± 2.7 mm Hg/s slope, ocular pulse amplitude (OPA) was 0.70 ± 0.13 mm Hg on average; the average K was 0.042 ± 0.010 µL-1 and average PV was 1.16 ± 0.43 µL. PV varied significantly between trials, days, and eyes (P ≤ 0.05). OPA was significantly correlated with K at native IOP: Pearson coefficients ranged from 0.71 to 0.83 (P ≤ 0.05) and R2 ranged from 0.50 to 0.69 (P ≤ 0.05) during the first trial. Conclusions: The MVI-driven ∆IOP and slope can be used to assess ocular coat mechanical behavior and measure ocular rigidity. Translational Relevance: Importantly, OPA at native IOP is correlated with ocular rigidity despite the significant variability in PV between heartbeats.

IOP, IOP Transient Impulse, Ocular Perfusion Pressure, and Mean Arterial Pressure Relationships in Nonhuman Primates Instrumented With Telemetry.

Purpose: To characterize relationships between intraocular pressure (IOP), mean arterial pressure (MAP), ocular perfusion pressure (OPP), IOP transient impulse, and IOP baseline impulse using continuous telemetry in nonhuman primates. Methods: We used our validated implantable telemetry system to wirelessly record bilateral IOP and arterial BP at 500 Hz in 7 eyes of 4 male rhesus macaques, aged 4 to 5 years. IOP, MAP, OPP, IOP transient impulse, and IOP baseline impulse were averaged into 1-hour periods over 20 days for each NHP. IOP transient impulse was defined as the portion of total IOP due to transient IOP fluctuations <0.5 seconds duration alone and IOP baseline impulse as the remaining area under the IOP versus time curve. OPP was defined as arterial BP-IOP (calculated continuously), and MAP was the hourly average of the continuous BP curve. Relationships between the variables were analyzed for each 24-hour period using either multivariate linear regression or Spearman Correlation Coefficients as appropriate. Results: Over twenty 24-hour periods, IOP transient impulse and OPP showed significant positive relationship in all eyes, which was driven largely by the data during waking hours. There was no significant relationship between IOP and MAP, IOP transient impulse and MAP, or IOP baseline impulse and IOP transient impulse. Conclusions: There are significant positive relationships between the frequency and/or size of transient IOP fluctuations (IOP transient impulse) and OPP. A possible explanation of this finding is that higher OPP, as well as a greater number of blinks and saccades (the primary sources of IOP transients), are associated with increased activity.