B80-4-43 Estimating the Elastic Modulus and Fracture Energy of Lung Tumors via Needle-induced Cavitation and Real-time Needle Tip Pressure Monitoring During Intratumoral Injections

Rationale

Intratumoral injection of anticancer agents into lung tumors under endobronchial ultrasound guidance is a strategy that aims to improve treatment efficacy and reduce systemic exposure and its associated side effects by concentrating the agent within the relevant tumor. During intratumoral injections at clinically applicable flow rates (on the order of ml/min), sequential fractures within the tumor are hypothesized to govern drug transport. At present, the parameters relevant to mathematically describe pressure induced tissue fracture are poorly characterized in lung tumors. Here, we present an estimate of the elastic modulus and fracture energy of a resected canine pulmonary carcinoma using the needle-induced cavitation framework.

Methods

A freshly resected canine pulmonary carcinoma (106.59g, 53mm x 44mm x 44mm) was injected with the contrast agent Visipaque (320mg/mL, GE Healthcare) at 0.1mL/min through an 18G needle using a syringe pump (PHD Ultra, Harvard Apparatus). Needle tip pressure was monitored throughout injection (SPR-1000, Millar Instruments, Houston, TX). The critical pressure (Pc) is defined as the initial major peak pressure and corresponds to the onset of cavitation. Pc was further used to determine the plane-strain elastic modulus using Equation 1 in Figure1C. After the major pressure peak, the subsequent pressure signal decay over the following 6 seconds was plotted on a log-log scale. The slope of decay fell in the range of a plane strain fracture. We, therefore, fitted our data to Equation 2 in Figure 1D.

Results

The elastic modulus was found to be 8.17 kPa, and the fracture energy was calculated to be 72.85 J/m2. The slope of the log-log linear regression was -0.326, which was well within the range of the plane-strain case considered in Equation 2 in Figure 1D.

Conclusions

Presented here is, to the best of our knowledge, the first published value for the tissue fracture energy of a lung tumor. At 72.85 J/m2, this value is higher than that previously published for healthy porcine lung tissue (13.8 ± 7.3 J/m2), whereas the elastic modulus of 8.17 kPa is within the range of previously published tumor data. A comprehensive estimation of the fracture energy across lung tumors can inform the maximum volume and the maximum flow rate that can be applied in lung tumors during intratumoral injections, thereby minimizing risks of extravasation and contributing to a personalized dosing and injection strategy.

This abstract is funded by: Johnson & Johnson Interventional Oncology