Real-time monitoring of thermal and mechanical response to sub-therapeutic HIFU beams in vivo

Abstract

We present first in vivo results of realtime 2D imaging of thermal and mechanical response to sub-therapeutic HIFU beams in a small-animal tumor model. A 2.5 MHz focused transducer with fnumber = 1.05 was used to generate short (≈ 1.5 sec) exposure in LNCap tumors implanted in the hindlimb of nude mice with power levels suitable to produce 4–6 °C rise in tissue (based on results in thermally-calibrated tissue mimicking phantoms). Beamformed RF data was collected at 99 frames per second to allow for capturing tissue displacements due to both temperature and breathing cycles. To ascertain the system's capability to cover an adequate range of periodic tissue motion, the sub-therapeutic HIFU beams were sinusoidally modulated at frequencies higher than the pulsatory frequency in the mouse model. Results from our previously published 2D temperature imaging algorithm demonstrate the capture of strains due to temperature change, pulsatory motions near arteries, and sinusoidal oscillations due to acoustic radiation force effects due to the HIFU-beam modulation. To reduce the effects of mechanical strains due to motion and ARF modulation, an iterative image reconstruction algorithm was used. The method employs alternating projections that employ the non-negativity constraints (TΔ(r, t) ≥ 0) and a multi-dimensional time-varying Gaussian filter derived from the spatio-temporal impulse response of the transient bioheat transfer equation (tBHTE) in each iteration. This method of projection onto convex sets (POCS) allows for the removal of artifacts inconsistent with the temperature evolution model in tissue media while preserving real temperature data until convergence is achieved. Our in vivo results show that the POCS algorithm achieves significant reduction in the temperature artifacts due to breathing and pulsations while preserving true temperature profiles with excellent spatial and temporal resolution. These results clearly demonstrate the sensitivity and specificity of ultrasound thermography to the spatially-confined sub-therapeutic HIFU beams. This performance is unmatched by other noninvasive methods for imaging temperature.