Chronic assessment of cerebral hemodynamics during rat forepaw electrical stimulation using functional ultrasound imaging.

Functional ultrasound imaging is a method recently developed to assess brain activity via hemodynamics in rodents. Doppler ultrasound signals allow the measurement of cerebral blood volume (CBV) and red blood cells' (RBCs') velocity in small vessels. However, this technique originally requires performing a large craniotomy that limits its use to acute experiments only. Moreover, a detailed description of the hemodynamic changes that underlie functional ultrasound imaging has not been described but is essential for a better interpretation of neuroimaging data. To overcome the limitation of the craniotomy, we developed a dedicated thinned skull surgery for chronic imaging. This procedure did not induce brain inflammation nor neuronal death as confirmed by immunostaining. We successfully acquired both high-resolution images of the microvasculature and functional movies of the brain hemodynamics on the same animal at 0, 2, and 7 days without loss of quality. Then, we investigated the spatiotemporal evolution of the CBV hemodynamic response function (HRF) in response to sensory-evoked electrical stimulus (1 mA) ranging from 1 (200 µs) to 25 pulses (5s). Our results indicate that CBV HRF parameters such as the peak amplitude, the time to peak, the full width at half-maximum and the spatial extent of the activated area increase with stimulus duration. Functional ultrasound imaging was sensitive enough to detect hemodynamic responses evoked by only a single pulse stimulus. We also observed that the RBC velocity during activation could be separated in two distinct speed ranges with the fastest velocities located in the upper part of the cortex and slower velocities in deeper layers. For the first time, functional ultrasound imaging demonstrates its potential to image brain activity chronically in small animals and offers new insights into the spatiotemporal evolution of cerebral hemodynamics.

Real-Time Passive Acoustic Mapping Using Sparse Matrix Multiplication.

Passive acoustic mapping enables the spatiotemporal monitoring of cavitation with circulating microbubbles during focused ultrasound (FUS)-mediated blood-brain barrier opening. However, the computational load for processing large data sets of cavitation maps or more complex algorithms limit the visualization in real-time for treatment monitoring and adjustment. In this study, we implemented a graphical processing unit (GPU)-accelerated sparse matrix-based beamforming and time exposure acoustics in a neuronavigation-guided ultrasound system for real-time spatiotemporal monitoring of cavitation. The system performance was tested in silico through benchmarking, in vitro using nonhuman primate (NHP) and human skull specimens, and demonstrated in vivo in NHPs. We demonstrated the stability of the cavitation map for integration times longer than 62.5 [Formula: see text]. A compromise between real-time displaying and cavitation map quality obtained from beamformed RF data sets with a size of 2000 ×128 ×30 (axial [Formula: see text]) was achieved for an integration time of [Formula: see text], which required a computational time of 0.27 s (frame rate of 3.7 Hz) and could be displayed in real-time between pulses at PRF = 2 Hz. Our benchmarking tests show that the GPU sparse-matrix algorithm processed the RF data set at a computational rate of [Formula: see text]/pixel/sample, which enables adjusting the frame rate and the integration time as needed. The neuronavigation system with real-time implementation of cavitation mapping facilitated the localization of the cavitation activity and helped to identify distortions due to FUS phase aberration. The in vivo test of the method demonstrated the feasibility of GPU-accelerated sparse matrix computing in a close to a clinical condition, where focus distortions exemplify problems during treatment. These experimental conditions show the need for spatiotemporal monitoring of cavitation with real-time capability that enables the operator to correct or halt the sonication in case substantial aberrations are observed.

Influence of Skin and Subcutaneous Tissue on High-Intensity Focused Ultrasound Beam: Experimental Quantification and Numerical Modeling.

High-intensity focused ultrasound (HIFU) enables the non-invasive thermal ablation of tumors. However, numerical simulations of the treatment remain complex and difficult to validate in clinically relevant situations. In this context, needle hydrophone measurements of the acoustic field downstream of seven rabbit tissue layers comprising skin, subcutaneous fat and muscle were performed in different geometrical configurations. Increasing curvature and thickness of the sample were found to decrease the focusing of the beam: typically, a curvature of 0.05 mm(-1) decreased the maximum pressure by 45% and doubled the focal area. A numerical model based on k-Wave Toolbox was found to be in very good agreement with the reported measurements. It was used to extrapolate the effect of the superficial tissues on peak positive and peak negative pressure at focus, which affects both cavitation and target heating. The shape of the interface was found to have a strong influence on the values, and it is therefore an important parameter to monitor or to control in the clinical practice. This also highlights the importance of modeling realistic configurations when designing treatment procedures.