Modulation of cardio-respiratory activity in mice via transcranial focused ultrasound.

OBJECTIVE: The objective of this study was to investigate the effect of FUS on autonomic nervous system activity, including heart and respiratory rates, and to separate the thermal modulation from combined thermal and mechanical FUS effects. METHODS: The thalamus and hypothalamus of wild-type mice were sonicated with a continuous-wave, 2 MHz FUS transducer at pressures of 425 and 850 kPa for 60 seconds. Cardiac and respiratory rates were monitored as signs of autonomic nervous activity. FUS-induced changes in autonomic activity were compared to FUS targeted to a spatially-distant motor region and to laser-induced heating. RESULTS: FUS delivered to the primary target over the thalamus and hypothalamus at 850 kPa reversibly increased the respiratory rate by 6.5±3.2 breaths per minute and decreased the heart rate by 3.2±1.8 beats per minute. No significant changes occurred in this region at 425 kPa or when targeting the motor regions at 850 kPa. Laser heating with the same temperature rise profile produced by 850 kPa sonication resulted in cardiorespiratory modulation similar to that of FUS. CONCLUSIONS: FUS is capable of reversibly and non-invasively modulating cardiorespiratory activity in mice. Localized changes in temperature may constitute the main cause for this activity, though further investigation is warranted into the distinct and complementary mechanisms of mechanically- and thermally-induced FUS neuromodulation. Close monitoring of vital signs during FUS neuromodulation may be warranted to monitor systemic responses to stimulation.

Iterative Curve Fitting of the Bioheat Transfer Equation for Thermocouple-Based Temperature Estimation In Vitro and In Vivo.

Temperature measurements with thin thermocouples embedded in ultrasound fields are strongly subjected to a viscous heating artifact (VHA). The artifact contribution decays over time; therefore, it can be minimized at late temperature readings. However, previous studies have failed to demonstrate a rigorous method for determining the optimal time point at which the artifact contribution is negligible. In this study, we present an iterative processing method based on successive curve fittings using an artifact-independent model. The fitting starting point moves at each iteration until the maximum R2 indicates where the viscous heating is minimum. A solution of the bioheat transfer equation is used to account for blood perfusion, thus enabling in vivo measurements. Three T-type thermocouples with different diameters and sensitivities were assessed in an excised canine liver and in the mouse brain in vivo. We found that the artifact constitutes up to 81% ± 5% of wire thermocouple readings. The best-fit time varied in the liver samples ( n = 3 ) from 0 to 3.335 ± 0.979 s and in the mouse brain ( n = 5 ) from 0 to 0.498 ± 0.457 s at variable experimental conditions, which clearly demonstrates the need of the method for finding the appropriate starting time point of the fit. This study introduces a statistical method to determine the best time to fit a curve that can back-estimate temperature in tissues under ultrasound exposure using thermocouples. This method allows temperature evaluation in vivo and in vitro during a validation and safety assessment of a wide range of therapeutic and diagnostic ultrasound modalities.