Objective: Primary and metastatic neoplasia of the liver are a significant source of morbidity and mortality. While surgical resection is the gold standard for management, <20% of these patients are surgical candidates. Minimally-invasive image-guided ablation techniques have shown significant promise as alternative or adjuvant treatments for this patient population. This preliminary investigation seeks to demonstrate the potential using gold nanoshells (NS) in liver to enhance both the safety and delivery of laser induced thermal therapy (LITT) to focal liver disease.

Methods: LITT of colorectal metastasis surrounded by liver parenchyma (+NS and -NS) was modeled using 3D FEM to evaluate the spatiotemporal distribution of temperature at various exposure times, powers and catheter locations. Tissue mimicking phantoms were irradiated under MR temperature imaging guidance using an MR compatible, actively-cooled laser applicator (808 nm) on a 1.5 T clinical MR scanner. Normal mongrel dogs (n=2) were intravenously infused with NS, their livers resected 24 hrs later, artificial “tumor” occlusions inserted, and were irradiated under MR temperature imaging guidance.

Results: NS accumulate significantly in liver after intravenous infusion. Simulations, phantom and ex vivo results demonstrated ablative levels of heating, conforming to the tumor volume, could be achieved for liver+NS. Simulations and phantoms demonstrated substantially less heating in liver-NS (Figure: Phantom treatment; 80s @ 10W; (a-b) liver+NS, (c) liver -NS).

Conclusions: Accumulated NS in liver parenchyma act as a “beam stop” for 808 nm photons during LITT, enhancing both safety of delivery by confining the beam to the tumor volume, regardless of fiber placement. NS in liver act as a heat source at the tumor margins and, due partly to the concave geometry, aids in the heating of the tumor. Results indicate that gold nanoshells in the liver may facilitate rapid, safe and controlled LITT heating for conformal liver tumor ablation. Such a technique may limit the number of applicators/applications needed to reliably treat larger tumors. In vivo studies are needed to verify and validate this.