Title:
Reduction of peak acoustic pressure and shaping of heated region by use of multifoci sonications in MR-guided high-intensity focused ultrasound mediated mild hyperthermia.

Abstract:
Ablative hyperthermia (>55 °C) has been used as a definitive treatment for accessible solid tumors not amenable to surgery, whereas mild hyperthermia (40-45 °C) has been shown effective as an adjuvant for both radiotherapy and chemotherapy. An optimal mild hyperthermia treatment is spatially accurate, with precise and homogeneous heating limited to the target region while also limiting the likelihood of unwanted thermal or mechanical bioeffects (tissue damage, vascular shutoff). Magnetic resonance imaging-guided high-intensity focused ultrasound (MR-HIFU) can noninvasively heat solid tumors under image-guidance. In a mild hyperthermia setting, a sonication approach utilizing multiple concurrent foci may provide the benefit of reducing acoustic pressure in the focal region (leading to reduced or no mechanical effects), while providing better control over the heating. The objective of this study was to design, implement, and characterize a multifoci sonication approach in combination with a mild hyperthermia heating algorithm, and compare it to the more conventional method of electronically sweeping a single focus.
Simulations (acoustic and thermal) and measurements (acoustic, with needle hydrophone) were performed. In addition, heating performance of multifoci and single focus sonications was compared using a clinical MR-HIFU platform in a phantom (target = 4-16 mm), in normal rabbit thigh muscle (target = 8 mm), and in a Vx2 tumor (target = 8 mm). A binary control algorithm was used for real-time mild hyperthermia feedback control (target range = 40.5-41 °C). Data were analyzed for peak acoustic pressure and intensity, heating energy efficiency, temperature accuracy (mean), homogeneity of heating (standard deviation [SD], T10 and T90), diameter and length of the heated region, and thermal dose (CEM(43)).
Compared to the single focus approach, multifoci sonications showed significantly lower (67% reduction) peak acoustic pressures in simulations and hydrophone measurements. In a rabbit Vx2 tumor, both single focus and multifoci heating approaches were accurate (mean = 40.82±0.12 °C [single] and 40.70±0.09 °C [multi]) and precise (standard deviation = 0.65±0.05 °C [single] and 0.64±0.04 °C [multi]), producing homogeneous heating (T(10-90) = 1.62 °C [single] and 1.41 °C [multi]). Heated regions were significantly shorter in the beam path direction (35% reduction, p < 0.05, Tukey) for multifoci sonications, i.e., resulting in an aspect ratio closer to one. Energy efficiency was lower for the multifoci approach. Similar results were achieved in phantom and rabbit muscle heating experiments.
A multifoci sonication approach was combined with a mild hyperthermia heating algorithm, and implemented on a clinical MR-HIFU platform. This approach resulted in accurate and precise heating within the targeted region with significantly lower acoustic pressures and spatially more confined heating in the beam path direction compared to the single focus sonication method.The reduction in acoustic pressure and improvement in spatial control suggest that multifoci heating is a useful tool in mild hyperthermia applications for clinical oncology.