Feasibility Study of Multi-application, Multi-Walled Carbon Nanotube for Magnetic Resonance Temperatrue Imaging Guided Laser Induced Thermal Therapy

In this work multi-application, multi-walled carbon nanotubes (MWCNTs) as super MR contrast agents and Near-Infared Radiation (NIR) laser absorbers are combined with Proton Resonance Frequency (PRF) based Magnetic Resonance Temperature Imaging (MRTI) to improve the safety and efficacy of Laser Induced Thermal Therapy (LITT). Instilled MWCNTs enable precise tumor localization and killing of the tumor through preferential high temperature while protecting surrounding healthy tissue by monitoring the 3D temperature distribution. As advanced MR contrast agents (CA), Fe-containing MWCNTs produced by chemical vapor deposition (CVD) with 600mg Ferrocene, show up to 5 times greater efficiency in changing T2 relaxation properties compared to the clinical MR CA, Feridex. Moreover, MWCNTs behave as super efficient dipole antennae and have a strong NIR absorbance, giving them potential use as a super heating generator in thermal ablation therapy. In this investigation MRTI-guided-MWCNTs-LITT was first evaluated using 3 tissue equivalent gel phantoms: alginate-only, MWCNTs-instilled and MWCNTs-implanted (sub-surface, simulating a subcutaneous tumor containing MWCNTs). For in vivo performance observations, 4 RENCA kidney tumors in their right flanks for four mice were thermally treated using an external laser beam after direct MWCNTs injection, and monitored by MRTI throughout the treatment. MRTI-guided-MWCNTs-LITT in phantom and in vivo experiments were performed using MR-compatible laser systems (fiber-optic and external laser beam) in a 7T MRI small animal scanner (Bruker Biospin). The 3D MRTI at 7T field strength provides high temporal resolution with reasonable special resolution, as well as accurate 3-D volume temperature measurement. Phantom results show that the MWCNTs–instilled phantom heated preferentially. During minimally-invasive fiber-optic laser heating (ø 0.6mm, 1 min @ 0.1W), (from 20°C to 47°C; Δt=+27°C), compared to the alginated-only phantom (from 20°C to 25°C; Δt=+5°C). With external non-invasive laser heating (ø 10mm, 0.5 min @ 1.8W), the implanted region of the MWCNTs-implanted phantom showed significantly elevated temperatures compared to the nearby alginate-only medium (Δt=+15°C). Similar temperature differentials were observed in vivo for the implanted RENCA kidney flank tumors with and without (with: maximum of 77°C, Δt=+51°C without: maximum of 44°C, Δt=+18°C) after a single 30s 3W/cm2 non-invasive laser irradiation. At two weeks post-treatment, a complete response was observed for flank tumors with MWCNTs + laser treatment, while no response was observed for flank tumors in two control groups that received no MWCNTs + laser or no MWCNTs and no laser. This investigation shows the successful combination of MWCNT and MRTI both in phantoms and in vivo for a small, pre-clinical study using flank tumors in mice. The in vivo results show significant improvement in tumor response for LITT with instilled MWCNTs, therefore, this technology shows feasibility and may be applicable for treatment of superficial tumors in humans.

Grantor dc:publisher

Wake Forest University

Year dc:date.issued

2009

Author dc:creator

• Xuanfeng, Ding

• Carbon Nanotube

Language dc:language.iso

en_US

Handle dc:identifier.uri

http://hdl.handle.net/10339/14806

OAI identifier oai:identifier

oai:wakespace.lib.wfu.edu:10339/14806