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

We present first in vivo results of realtime 2D imaging of thermal andmechanical response to sub-therapeutic HIFU beams in a small-animal tumor model.A 2.5 MHz focused transducer with f_number 1.05 was used to generateshort (1.5 sec) exposure in LNCap tumors implanted in the hindlimb of nude micewith power levels suitable to produce 4-6 C rise in tissue (based on results inthermally-calibrated tissue mimicking phantoms). Beamformed RF data wascollected at 99 frames per second to allow for capturing tissue displacementsdue to both temperature and breathing cycles. To ascertain the system'scapability to cover an adequate range of periodic tissue motion, thesub-therapeutic HIFU beams were sinusoidally modulated at frequencies higherthan the pulsatory frequency in the mouse model. Results from our previouslypublished 2D temperature imaging algorithm demonstrate the capture of strainsdue to temperature change, pulsatory motions near arteries, and sinusoidaloscillations due to acoustic radiation force effects due to the HIFU-beammodulation. To reduce the effects of mechanical strains due to motion and ARFmodulation, an iterative image reconstruction algorithm was used. The methodemploys alternating projections that employ the non-negativity constraints (T(r,t) 0) and a multi-dimensional time-varying Gaussian filter derived from thespatio-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 evolutionmodel in tissue media while preserving real temperature data until convergenceis achieved. Our in vivo results show that the POCS algorithm achievessignificant reduction in the temperature artifacts due to breathing andpulsations while preserving true temperature profiles with excellent spatial andtemporal resolution. These results clearly demonstrate the sensitivity andspecificity of ultrasound thermography to the spatially-confined sub-therapeuticHIFU beams. This performance is unmatched by other noninvasive methods forimaging temperature.