High wall shear stress (WSS) and near-infrared spectroscopy (NIRS) detected lipid-rich plaque (LRP) are both known to be associated with plaque destabilization and future adverse cardiovascular events. However, knowledge of spatial co-localization of LRP and high WSS is lacking. This study investigated the co-localization of LRP based on NIRS and high WSS. Fifty-three patients presenting acute coronary syndrome underwent NIRS-intravascular-ultrasound (NIRS-IVUS) imaging of a non-culprit coronary artery. WSS was obtained using WSS profiling in 3D-reconstructions of the coronary arteries based on fusion of IVUS-segmented lumen and CT-derived 3D-centerline. Thirty-eight vessels were available for final analysis and divided into 0.5 mm/45° sectors. LRP sectors, as identified by NIRS, were more often colocalized with high WSS than sectors without LRP. Moreover, there was a dose-dependent relationship between lipid content and high WSS exposure. This study is a first step in understanding the evolution of LRPs to vulnerable plaques.

Ultrasound insonification of microbubbles can locally enhance drug delivery, but the microbub-bleÀcell interaction remains poorly understood. Because intracellular calcium (Ca 2þ i) is a key cellular regulator, unraveling the Ca 2þ i fluctuations caused by an oscillating microbubble provides crucial insight into the underlying bio-effects. Therefore, we developed an optical imaging system at nanometer and nanosecond resolution that can resolve Ca 2þ i fluctuations and microbubble oscillations. Using this system, we clearly distinguished three Ca 2þ i uptake profiles upon sonoporation of endothelial cells, which strongly correlated with the microbubble oscillation amplitude, severity of sonoporation and opening of cellÀcell contacts. We found a narrow operating range for viable drug delivery without lethal cell damage. Moreover, adjacent cells were affected by a calcium wave propagating at 15 mm/s. With the unique optical system, we unraveled the microbubble oscillation behavior required for drug delivery and Ca 2þ i fluctuations, providing new insight into the microbubbleÀcell interaction to aid clinical translation.

Prospective identification of lipid-rich vulnerable plaque has remained an elusive goal. Intravascular photoacoustics, a hybrid optical and ultrasonic technology, was developed as a tool for lipid-rich plaque imaging. Here, we present the first in vivo images of lipid-rich coronary atherosclerosis acquired with this new technology in a large animal model, and relate them to independent catheter-based imaging and histology.

Highlights-We describe a novel ultrafast functional ultrasound technique (HDfUS) -HDfUS offers continuous recording with unmatched spatiotemporal resolution -HDfUS allows to resolve complex 4D neurovascular responses in the brain -First fUS study on non-mammalian species AbstractRecent advances in ultrasound Doppler imaging have allowed to visualize brain activity in small mammalian species such as rats and mice. In birds, this type of functional ultrasound imaging was impossible up to now because birds have physiological characteristics that are unfavorable for current functional ultrasound acquisition schemes. Here, we introduce a high-definition functional ultrasound acquisition method (HDfUS) acquiring 20,000 frames per second continuously. This enabled first successful functional studies on awake pigeons subjected to auditory and visual stimulation. We show that the improved spatiotemporal resolution and sensitivity of HDfUS allows to visualize and investigate the temporally resolved 3D neural activity evoked by a complex stimulation pattern, such as a moving light source. This illustrates the enormous potential of HDfUS imaging to become a new standard functional brain imaging method revealing unknown, stimulus related hemodynamics at excellent signal-to-noise ratio and spatiotemporal resolution. KeywordsHigh definition functional ultrasound imaging Real time ultrafast Doppler 3D pigeon brain Visual and auditory stimulation