Human brain mapping using co-registered fUS, fMRI and ESM during awake brain surgeries: A proof-of-concept study.

Accurate, depth-resolved functional imaging is key in both understanding and treatment of the human brain. A new sonography-based imaging technique named functional Ultrasound (fUS) uniquely combines high sensitivity with submillimeter-subsecond spatiotemporal resolution available in large fields-of-view. In this proof-of-concept study we show that: (A) fUS reveals the same eloquent regions as found by fMRI while concomitantly visualizing in-vivo microvascular morphology underlying these functional hemodynamics and (B) fUS-based functional maps are confirmed by Electrocortical Stimulation Mapping (ESM), the current gold-standard in awake neurosurgical practice.

Coupling Two Ultra-high-Speed Cameras to Elucidate Ultrasound Contrast-Mediated Imaging and Therapy.

Ultrasound contrast-mediated medical imaging and therapy both rely on the dynamics of micron- and nanometer-sized ultrasound cavitation nuclei, such as phospholipid-coated microbubbles and phase-change droplets. Ultrasound cavitation nuclei respond non-linearly to ultrasound on a nanosecond time scale that necessitates the use of ultra-high-speed imaging to fully visualize these dynamics in detail. In this study, we developed an ultra-high-speed optical imaging system that can record up to 20 million frames per second (Mfps) by coupling two small-sized, commercially available, 10-Mfps cameras.

Real-Time Coded Excitation Imaging Using a CMUT-Based Side Looking Array for Intravascular Ultrasound.

Intravascular ultrasound (IVUS) is a well-established diagnostic method that provides images of the vessel wall and atherosclerotic plaques. We investigate the potential for phased-array IVUS utilizing coded excitation (CE) for improving the penetration depth and image signal-to-noise ratio (SNR). It is realized on a new experimental broadband capacitive micromachined ultrasound transducer (CMUT) array, operated in collapse mode, with 96 elements placed at the circumference of a catheter tip with a 1.

Lipid-rich Plaques Detected by Near-infrared Spectroscopy Are More Frequently Exposed to High Shear Stress.

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.

High-Resolution Imaging of Intracellular Calcium Fluctuations Caused by Oscillating Microbubbles.

Ultrasound insonification of microbubbles can locally enhance drug delivery, but the microbubble-cell interaction remains poorly understood. Because intracellular calcium (Ca) is a key cellular regulator, unraveling the Ca 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 fluctuations and microbubble oscillations.

Opening of endothelial cell-cell contacts due to sonoporation.

Ultrasound insonification of microbubbles can locally increase vascular permeability to enhance drug delivery. To control and optimize the therapeutic potential, we need to better understand the underlying biological mechanisms of the drug delivery pathways. The aim of this in vitro study was to elucidate the microbubble-endothelial cell interaction using the Brandaris 128 ultra-high-speed camera (up to 25 Mfps) coupled to a custom-built Nikon confocal microscope, to visualize both microbubble oscillation and the cellular response.

Functional Ultrasound (fUS) During Awake Brain Surgery: The Clinical Potential of Intra-Operative Functional and Vascular Brain Mapping.

Background And Purpose: Oncological neurosurgery relies heavily on making continuous, intra-operative tumor-brain delineations based on image-guidance. Limitations of currently available imaging techniques call for the development of real-time image-guided resection tools, which allow for reliable functional and anatomical information in an intra-operative setting. Functional ultrasound (fUS), is a new mobile neuro-imaging tool with unprecedented spatiotemporal resolution, which allows for the detection of small changes in blood dynamics that reflect changes in metabolic activity of activated neurons through neurovascular coupling.

Real-time photoacoustic assessment of radiofrequency ablation lesion formation in the left atrium.

In interventional electrophysiology, catheter-based radiofrequency (RF) ablation procedures restore cardiac heart rhythm by interrupting aberrant conduction paths. Real-time feedback on lesion formation and post-treatment lesion assessment could overcome procedural challenges related to ablation of underlying structures and lesion gaps. This study aims to evaluate real-time visualization of lesion progression and continuity during intra-atrial ablation with photoacoustic (PA) imaging, using clinically deployable technology.

Simultaneous Morphological and Flow Imaging Enabled by Megahertz Intravascular Doppler Optical Coherence Tomography.

We demonstrate three-dimensional intravascular flow imaging compatible with routine clinical image acquisition workflow by means of megahertz (MHz) intravascular Doppler Optical Coherence Tomography (OCT). The OCT system relies on a 1.1 mm diameter motorized imaging catheter and a 1.

Combined Confocal Microscope and Brandaris 128 Ultra-High-Speed Camera.

Controlling microbubble-mediated drug delivery requires the underlying biological and physical mechanisms to be unraveled. To image both microbubble oscillation upon ultrasound insonification and the resulting cellular response, we developed an optical imaging system that can achieve the necessary nanosecond temporal and nanometer spatial resolutions. We coupled the Brandaris 128 ultra-high-speed camera (up to 25 million frames per second) to a custom-built Nikon A1R+ confocal microscope.

In vivo intravascular photoacoustic imaging of plaque lipid in coronary atherosclerosis.

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.

Validation of Resting Diastolic Pressure Ratio Calculated by a Novel Algorithm and Its Correlation With Distal Coronary Artery Pressure to Aortic Pressure, Instantaneous Wave-Free Ratio, and Fractional Flow Reserve.

Background: Instantaneous wave-free ratio (iFR) offers a reliable non-hyperemic assessment of coronary physiology but requires dedicated proprietary software with a fully automated algorithm. We hypothesized that dPR (diastolic pressure ratio), calculated with novel universal software, has a strong correlation with iFR, similar diagnostic accuracy relative to resting distal coronary artery pressure/aortic pressure and fractional flow reserve (FFR).

Methods And Results: The dPR study is an observational, retrospective, single-center cohort study including patients who underwent iFR or FFR.

3D functional ultrasound imaging of pigeons.

Recent advances in ultrasound Doppler imaging have facilitated the technique of functional ultrasound (fUS) which enables visualization of brain-activity due to neurovascular coupling. As of yet, this technique has been applied to rodents as well as to human subjects during awake craniotomy surgery and human newborns. Here we demonstrate the first successful fUS studies on awake pigeons subjected to auditory and visual stimulation.

Sparse Ultrasound Image Reconstruction From a Shape-Sensing Single-Element Forward-Looking Catheter.

Objective: Minimally invasive procedures, such as intravascular and intracardiac interventions, may benefit from guidance with forward-looking (FL) ultrasound. In this work, we investigate FL ultrasound imaging using a single-element transducer integrated in a steerable catheter, together with an optical shape sensing (OSS) system.

Methods: We tested the feasibility of the proposed device by imaging the surface of a tissue-mimicking (TM) phantom and an ex vivo human carotid plaque.

Compressive 3D ultrasound imaging using a single sensor.

Three-dimensional ultrasound is a powerful imaging technique, but it requires thousands of sensors and complex hardware. Very recently, the discovery of compressive sensing has shown that the signal structure can be exploited to reduce the burden posed by traditional sensing requirements. In this spirit, we have designed a simple ultrasound imaging device that can perform three-dimensional imaging using just a single ultrasound sensor.

Focal areas of increased lipid concentration on the coating of microbubbles during short tone-burst ultrasound insonification.

Acoustic behavior of lipid-coated microbubbles has been widely studied, which has led to several numerical microbubble dynamics models that incorporate lipid coating behavior, such as buckling and rupture. In this study we investigated the relationship between microbubble acoustic and lipid coating behavior on a nanosecond scale by using fluorescently labeled lipids. It is hypothesized that a local increased concentration of lipids, appearing as a focal area of increased fluorescence intensity (hot spot) in the fluorescence image, is related to buckling and folding of the lipid layer thereby highly influencing the microbubble acoustic behavior.

Real-time volumetric lipid imaging in vivo by intravascular photoacoustics at 20 frames per second.

Lipid deposition can be assessed with combined intravascular photoacoustic/ultrasound (IVPA/US) imaging. To date, the clinical translation of IVPA/US imaging has been stalled by a low imaging speed and catheter complexity. In this paper, we demonstrate imaging of lipid targets in swine coronary arteries in vivo, at a clinically useful frame rate of 20 s.

Measuring submicrometer displacement vectors using high-frame-rate ultrasound imaging.

Measuring the magnitude and direction of tissue displacement provides the basis for the assessment of tissue motion or tissue stiffness. Using conventional displacement tracking by ultrasound delay estimation, only one direction of tissue displacement can be estimated reliably. In this paper, we describe a new technique for estimating the complete two-dimensional displacement vector using high-frame-rate ultrasound imaging.

Unique pumping-out fracturing mechanism of a polymer-shelled contrast agent: an acoustic characterization and optical visualization.

This work describes the fracturing mechanism of air-filled microbubbles (MBs) encapsulated by a cross-linked poly(vinyl alcohol) (PVA) shell. The radial oscillation and fracturing events following the ultrasound exposure were visualized with an ultrahigh-speed camera, and backscattered timedomain signals were acquired with the acoustic setup specific for harmonic detection. No evidence of gas emerging from defects in the shell with the arrival of the first insonation burst was found.

High-definition imaging of carotid artery wall dynamics.

The carotid artery (CA) is central to cardiovascular research, because of the clinical relevance of CA plaques as culprits of stroke and the accessibility of the CA for cardiovascular screening. The viscoelastic state of this artery, essential for clinical evaluation, can be assessed by observing arterial deformation in response to the pressure changes throughout the cardiac cycle. Ultrasound imaging has proven to be an excellent tool to monitor these dynamic deformation processes.

Plane-wave ultrasound beamforming using a nonuniform fast Fourier transform.

Beamforming of plane-wave ultrasound echo signals in the Fourier domain provides fast and accurate image reconstruction. Conventional implementations perform a k-space interpolation from the uniform sampled grid to a nonuniform acoustic dispersion grid. In this paper, we demonstrate that this step can be replaced by a nonuniform Fourier transform.

Brandaris 128 ultra-high-speed imaging facility: 10 years of operation, updates, and enhanced features.

The Brandaris 128 ultra-high-speed imaging facility has been updated over the last 10 years through modifications made to the camera's hardware and software. At its introduction the camera was able to record 6 sequences of 128 images (500 × 292 pixels) at a maximum frame rate of 25 Mfps. The segmented mode of the camera was revised to allow for subdivision of the 128 image sensors into arbitrary segments (1-128) with an inter-segment time of 17 μs.

High shear stress induces a strain increase in human coronary plaques over a 6-month period.

Aims: Atherosclerotic plaques develop in low shear stress regions. In the more advanced phase of the disease, plaques are exposed to altered shear stress levels, which could influence plaque composition. We investigated changes in plaque composition in human coronary arteries over a 6-month period and how these changes are related to shear stress.