Penetrating neural probe technologies allow investigators to record electrical signals in the brain. Implantation of probes causes acute tissue damage, partially due to vasculature disruption during probe implantation. This trauma can cause abnormal electrophysiological responses, temporary increases in neurotransmitter levels, and perpetuate chronic immune responses. A significant challenge for investigators is examining neurovascular features below the surface of the brain in vivo. The objective of this study was to investigate localized bleeding resulting from inserting microscale neural probes into cortex using two-photon microscopy (TPM) and to explore an approach to minimize blood vessel disruption through insertion methods and probe design. 3D TPM images of cortical neurovasculature were obtained from mice and used to select preferred insertion positions for probe insertion to reduce neurovasculature damage. There was an 82.8±14.3% reduction in neurovascular damage for probes inserted in regions devoid of major (> 5 µm) sub-surface vessels. Also, the deviation of surface vessels from the vector normal to the surface as a function of depth and vessel diameter was measured and characterized. 68% of the major vessels were found to deviate less than 49 µm from their surface origin up to a depth of 500 µm. Inserting probes more than 49 µm from major surface vessels can reduce chances of severing major sub-surface neurovasculature without using TPM.
In open surgical procedures, image-ablate ultrasound arrays performed thermal ablation and imaging on rabbit liver lobes with implanted VX2 tumor. Treatments included unfocused (bulk ultrasound ablation, N = 10) and focused (high-intensity focused ultrasound ablation, N = 13) exposure conditions. Echo decorrelation and integrated backscatter images were formed from pulse-echo data recorded during rest periods after each therapy pulse. Echo decorrelation images were corrected for artifacts using decorrelation measured prior to ablation. Ablation prediction performance was assessed using receiver operating characteristic curves. Results revealed significantly increased echo decorrelation and integrated backscatter in both ablated liver and ablated tumor relative to unablated tissue, with larger differences observed in liver than in tumor. For receiver operating characteristic curves computed from all ablation exposures, both echo decorrelation and integrated backscatter predicted liver and tumor ablation with statistically significant success, and echo decorrelation was significantly better as a predictor of liver ablation. These results indicate echo decorrelation imaging is a successful predictor of local thermal ablation in both normal liver and tumor tissue, with potential for real-time therapy monitoring.
Echo decorrelation imaging, a method for mapping ablation-induced ultrasound echo changes, is analyzed. Local echo decorrelation is shown to approximate the decoherence spectrum of tissue reflectivity. Effects of the ultrasound measurement system, echo signal windowing, electronic noise, and tissue motion on echo decorrelation images are determined theoretically, leading to a method for reduction of motion and noise artifacts. Theoretical analysis is validated by simulations and experiments. Simulated decoherence of the scattering medium was recovered with root-mean-square error less than 10% with accuracy dependent on the correlation window size. Motion-induced decorrelation measured in an ex vivo pubovisceral muscle model showed similar trends to theoretical motion-induced decorrelation for a 2.1 MHz curvilinear array with decorrelation approaching unity for 3-4 mm elevational displacement or 1-1.6 mm range displacement. For in vivo imaging of porcine liver by a 7 MHz linear array, theoretical decorrelation computed using image-based motion estimates correlated significantly with measured decorrelation (r = 0.931, N = 10). Echo decorrelation artifacts incurred during in vivo radiofrequency ablation in the same porcine liver were effectively compensated based on the theoretical echo decorrelation model and measured pre-treatment decorrelation. These results demonstrate the potential of echo decorrelation imaging for quantification of heat-induced changes to the scattering tissue medium during thermal ablation.
The ability to control high-intensity focused ultrasound (HIFU) thermal ablation using echo decorrelation imaging feedback was evaluated in ex vivo bovine liver. Sonications were automatically ceased when the minimum cumulative echo decorrelation within the region of interest exceeded an ablation control threshold, determined from preliminary experiments as -2.7 (log-scaled decorrelation per millisecond), corresponding to 90% specificity for local ablation prediction. Controlled HIFU thermal ablation experiments were compared with uncontrolled experiments employing two, five or nine sonication cycles. Means and standard errors of the lesion width, area and depth, as well as receiver operating characteristic curves testing ablation prediction performance, were computed for each group. Controlled trials exhibited significantly smaller average lesion area, width and treatment time than five-cycle or nine-cycle uncontrolled trials and also had significantly greater prediction capability than two-cycle uncontrolled trials. These results suggest echo decorrelation imaging is an effective approach to real-time HIFU ablation control.
This paper demonstrates the ability to form sound speed images using two opposed commercial linear arrays to mimic ultrasound image acquisition in the compressed mammographic geometry. The ability to create reasonably good speed of sound images in the compressed mammographic geometry allows images to be readily coregistered to tomosynthesis image volumes for breast cancer detection and characterization studies.
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