Comparison and Optimization of Insonation Strategies for Contrast Enhanced Ultrasound Imaging

Evolution of vulnerable carotid plaques are crucial reason for cerebral ischemic strokes and identifying them in the early stage can become very important in avoiding the risk of stroke. In order to improve the identification and quantification accuracy of infancy plaques better visualization techniques are needed. Improving the visualization and quantification of neovascularization in carotid plaque using contrast enhanced ultrasound imaging still remains a challenging task. In this thesis work, three optimization techniques are proposed, which showed an improvement in the sensitivity of contrast agents when compared to the conventional clinical settings and insonation strategies. They are as follows:1) Insonation at harmonic specific (2nd harmonic) resonance frequency instead of resonance frequency based on maximum energy absorption provides enhanced nonlinear contribution.2) At high frequency ultrasound imaging, shorter pulse length will provide improved harmonic signal content when compared to longer pulse lengths. Applying this concept to multi- pulse sequencing (Pulse Inversion and Cadence contrast pulse sequencing) resulted in increased magnitude of the remaining harmonic signal after pulse summations.3) Peak negative pressure optimization of Pulse Inversion and Cadence contrast pulse sequencing was showed to further enhance the nonlinear content of the backscattered signal from contrast microbubbles without increasing the safety limits, defined by the mechanical index.The results presented in this thesis are based on computational modeling (Bubblesim software) and as a future continuation we plan to verify the simulation results with vitro studies

Aversive state processing in the posterior insular cortex

Triggering behavioral adaptation upon the detection of adversity is crucial for survival. The insular cortex has been suggested to process emotions and homeostatic signals, but how the insular cortex detects internal states and mediates behavioral adaptation is poorly understood. By combining data from fiber photometry, optogenetics, awake two-photon calcium imaging and comprehensive whole-brain viral tracings, we here uncover a role for the posterior insula in processing aversive sensory stimuli and emotional and bodily states, as well as in exerting prominent top-down modulation of ongoing behaviors in mice. By employing projection-specific optogenetics, we describe an insula-to-central amygdala pathway to mediate anxiety-related behaviors, while an independent nucleus accumbens-projecting pathway regulates feeding upon changes in bodily state. Together, our data support a model in which the posterior insular cortex can shift behavioral strategies upon the detection of aversive internal states, providing a new entry point to understand how alterations in insula circuitry may contribute to neuropsychiatric conditions