Four-dimensional computational ultrasound imaging of brain hemodynamics.

Four-dimensional ultrasound imaging of complex biological systems such as the brain is technically challenging because of the spatiotemporal sampling requirements. We present computational ultrasound imaging (cUSi), an imaging method that uses complex ultrasound fields that can be generated with simple hardware and a physical wave prediction model to alleviate the sampling constraints. cUSi allows for high-resolution four-dimensional imaging of brain hemodynamics in awake and anesthetized mice.

Time-resolved absolute radius estimation of vibrating contrast microbubbles using an acoustical camera.

Ultrasound (US) contrast agents consist of microbubbles ranging from 1 to 10 µm in size. The acoustical response of individual microbubbles can be studied with high-frame-rate optics or an "acoustical camera" (AC). The AC measures the relative microbubble oscillation while the optical camera measures the absolute oscillation. In this article, the capabilities of the AC are extended to measure the absolute oscillations. In the AC setup, microbubbles are insonified with a high- (25 MHz) and low-frequency US wave (1-2.5 MHz). Other than the amplitude modulation (AM) from the relative size change of the microbubble (employed in Renaud, Bosch, van der Steen, and de Jong (2012a). "An 'acoustical camera' for in vitro characterization of contrast agent microbubble vibrations," Appl. Phys. Lett. 100(10), 101911, the high-frequency response from individual vibrating microbubbles contains a phase modulation (PM) from the microbubble wall displacement, which is the extension described here. The ratio of PM and AM is used to determine the absolute radius, R0. To test this sizing, the size distributions of two monodisperse microbubble populations ( R = 2.1 and 3.5 µm) acquired with the AC were matched to the distribution acquired with a Coulter counter. As a result of measuring the absolute size of the microbubbles, this "extended AC" can capture the full radial dynamics of single freely floating microbubbles with a throughput of hundreds of microbubbles per hour.

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. We have applied fUS during conventional awake brain surgery to determine its clinical potential for both intra-operative functional and vascular brain mapping, with the ultimate aim of achieving maximum safe tumor resection. METHODS: During awake brain surgery, fUS was used to image tumor vasculature and task-evoked brain activation with electrocortical stimulation mapping (ESM) as a gold standard. For functional imaging, patients were presented with motor, language or visual tasks, while the probe was placed over (ESM-defined) functional brain areas. For tumor vascular imaging, tumor tissue (pre-resection) and tumor resection cavity (post-resection) were imaged by moving the hand-held probe along a continuous trajectory over the regions of interest. RESULTS: A total of 10 patients were included, with predominantly intra-parenchymal frontal and temporal lobe tumors of both low and higher histopathological grades. fUS was able to detect (ESM-defined) functional areas deep inside the brain for a range of functional tasks including language processing. Brain tissue could be imaged at a spatial and temporal resolution of 300 µm and 1.5-2.0 ms respectively, revealing real-time tumor-specific, and healthy vascular characteristics. CONCLUSION: The current study presents the potential of applying fUS during awake brain surgery. We illustrate the relevance of fUS for awake brain surgery based on its ability to capture both task-evoked functional cortical responses as well as differences in vascular characteristics between tumor and healthy tissue. As current neurosurgical practice is still pre-dominantly leaning on inherently limited pre-operative imaging techniques for tumor resection-guidance, fUS enters the scene as a promising alternative that is both anatomically and physiologically informative.

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. To allow successful fUS on pigeons we improved the temporal resolution of fUS up to 20,000 frames per second with real-time visualization and continuous recording. We show that this gain in temporal resolution significantly increases the sensitivity for detecting small fluctuations in cerebral blood flow and volume which may reflect increased local neural activity. Through this increased sensitivity we were able to capture the elaborate 3D neural activity pattern evoked by a complex stimulation pattern, such as a moving light source. By pushing the limits of fUS further, we have reaffirmed the enormous potential of this technique as a new standard in functional brain imaging with the capacity to unravel unknown, stimulus related hemodynamics with excellent spatiotemporal resolution with a wide field of view.

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. Our device makes a compressed measurement of the spatial ultrasound field using a plastic aperture mask placed in front of the ultrasound sensor. The aperture mask ensures that every pixel in the image is uniquely identifiable in the compressed measurement. We demonstrate that this device can successfully image two structured objects placed in water. The need for just one sensor instead of thousands paves the way for cheaper, faster, simpler, and smaller sensing devices and possible new clinical applications.

Segmentation of multiple heart cavities in 3-D transesophageal ultrasound images.

Three-dimensional transesophageal echocardiography (TEE) is an excellent modality for real-time visualization of the heart and monitoring of interventions. To improve the usability of 3-D TEE for intervention monitoring and catheter guidance, automated segmentation is desired. However, 3-D TEE segmentation is still a challenging task due to the complex anatomy with multiple cavities, the limited TEE field of view, and typical ultrasound artifacts. We propose to segment all cavities within the TEE view with a multi-cavity active shape model (ASM) in conjunction with a tissue/blood classification based on a gamma mixture model (GMM). 3-D TEE image data of twenty patients were acquired with a Philips X7-2t matrix TEE probe. Tissue probability maps were estimated by a two-class (blood/tissue) GMM. A statistical shape model containing the left ventricle, right ventricle, left atrium, right atrium, and aorta was derived from computed tomography angiography (CTA) segmentations by principal component analysis. ASMs of the whole heart and individual cavities were generated and consecutively fitted to tissue probability maps. First, an average whole-heart model was aligned with the 3-D TEE based on three manually indicated anatomical landmarks. Second, pose and shape of the whole-heart ASM were fitted by a weighted update scheme excluding parts outside of the image sector. Third, pose and shape of ASM for individual heart cavities were initialized by the previous whole heart ASM and updated in a regularized manner to fit the tissue probability maps. The ASM segmentations were validated against manual outlines by two observers and CTA derived segmentations. Dice coefficients and point-to-surface distances were used to determine segmentation accuracy. ASM segmentations were successful in 19 of 20 cases. The median Dice coefficient for all successful segmentations versus the average observer ranged from 90% to 71% compared with an inter-observer range of 95% to 84%. The agreement against the CTA segmentations was slightly lower with a median Dice coefficient between 85% and 57%. In this work, we successfully showed the accuracy and robustness of the proposed multi-cavity segmentation scheme. This is a promising development for intraoperative procedure guidance, e.g., in cardiac electrophysiology.

Improved Segmentation of Multiple Cavities of the Heart in Wide-View 3-D Transesophageal Echocardiograms.

Minimally invasive interventions in the heart such as in electrophysiology are becoming more and more important in clinical practice. Currently, preoperative computed tomography angiography (CTA) is used to provide anatomic information during electrophysiology interventions, but this does not provide real-time feedback and burdens the patient with additional radiation and side effects of the contrast agent. Three-dimensional transesophageal echocardiography (TEE) is an excellent modality for visualization of anatomic structures and instruments in real time, but some cavities, especially the left atrium, suffer from the limited coverage of the 3-D TEE volumes. This leads to difficulty in segmenting the left atrium. We propose replacing or complementing pre-operative CTA imaging with wide-view TEE. We tested this proposal on 20 patients for which TEE image volumes covering the left atrium and CTA images were acquired. The TEE images were manually registered, and wide-view volumes were generated. Five heart cavities in single-view and wide-view TEE were segmented and compared with atlas based-segmentations derived from the CTA images. We found that the segmentation accuracy (Dice coefficients) improved relative to segmentation of single-view images by 5, 15 and 9 percentage points for the left atrium, right atrium and aorta, respectively. Average anatomic coverage was improved by 2, 29, 62 and 49 percentage points for the right ventricle, left atrium, right atrium and aorta, respectively. This finding confirms that wide-view 3-D TEE can be useful in supporting electrophysiology interventions.

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. We describe how a new technique called high-frame-rate ultrasound imaging captures the tissue deformation dynamics throughout the cardiac cycle in unprecedented detail. Local tissue motion exhibits distinct features of sub-micrometer displacements on a sub-millisecond time scale. We present a high-definition motion analysis technique based on plane wave ultrasound imaging able to capture these features. We validated this method by screening a group of healthy volunteers and compared the results with those for two patients known to have atherosclerosis to illustrate the potential utility of this technique.

Very different performance of the power Doppler modalities of several ultrasound machines ascertained by a microvessel flow phantom.

INTRODUCTION: In many patients with rheumatoid arthritis (RA) subclinical disease activity can be detected with ultrasound (US), especially using power Doppler US (PDUS). However, PDUS may be highly dependent on the type of machine. This could create problems both in clinical trials and in daily clinical practice. To clarify how the PDUS signal differs between machines we created a microvessel flow phantom. METHODS: The flow phantom contained three microvessels (150, 1000, 2000 microns). A syringe pump was used to generate flows. Five US machines were used. Settings were optimised to assess the lowest detectable flow for each US machine. RESULTS: The minimal detectable flow velocities showed very large differences between the machines. Only two of the machines may be able to detect the very low flows in the capillaries of inflamed joints. There was no clear relation with price. One of the lower-end machines actually performed best in all three vessel sizes. CONCLUSIONS: We created a flow phantom to test the sensitivity of US machines to very low flows in small vessels. The sensitivity of the power Doppler modalities of 5 different machines was very different. The differences found between the machines are probably caused by fundamental differences in processing of the PD signal or internal settings inaccessible to users. Machines considered for PDUS assessment of RA patients should be tested using a flow phantom similar to ours. Within studies, only a single machine type should be used.