Real-time 3-D contrast-enhanced transcranial ultrasound and aberration correction.

Contrast-enhanced (CE) transcranial ultrasound (US) and reconstructed 3-D transcranial ultrasound have shown advantages over traditional methods in a variety of cerebrovascular diseases. We present the results from a novel ultrasound technique, namely real-time 3-D contrast-enhanced transcranial ultrasound. Using real-time 3-D (RT3D) ultrasound and microbubble contrast agent, we scanned 17 healthy volunteers via a single temporal window and nine via the suboccipital window and report our detection rates for the major cerebral vessels. In 71% of subjects, both of our observers identified the ipsilateral circle of Willis from the temporal window, and in 59% we imaged the entire circle of Willis. From the suboccipital window, both observers detected the entire vertebrobasilar circulation in 22% of subjects, and in 44%, the basilar artery. After performing phase aberration correction on one subject, we were able to increase the diagnostic value of the scan, detecting a vessel not present in the uncorrected scan. These preliminary results suggest that RT3D CE transcranial US and RT3D CE transcranial US with phase aberration correction have the potential to greatly impact the field of neurosonology.

Phase-aberration correction with a 3-D ultrasound scanner: feasibility study.

We tested the feasibility of using adaptive imaging, namely phase-aberration correction, with two-dimensional (2-D) arrays and real-time, 3-D ultrasound. Because of the high spatial frequency content of aberrators, 2-D arrays, which generally have smaller pitch and thus higher spatial sampling frequency, and 3-D imaging show potential to improve the performance of adaptive imaging. Phase-correction algorithms improve image quality by compensating for tissue-induced errors in beamforming. Using the illustrative example of transcranial ultrasound, we have evaluated our ability to perform adaptive imaging with a real-time, 3-D scanner. We have used a polymer casting of a human temporal bone, root-mean-square (RMS) phase variation of 45.0 ns, full-width-half-maximum (FWHM) correlation length of 3.35 mm, and an electronic aberrator, 100 ns RMS, 3.76 mm correlation, with tissue phantoms as illustrative examples of near-field, phase-screen aberrators. Using the multilag, least-squares, cross-correlation method, we have shown the ability of 3-D adaptive imaging to increase anechoic cyst identification, image brightness, contrast-to-speckle ratio (CSR), and, in 3-D color Doppler experiments, the ability to visualize flow. For a physical aberrator skull casting we saw CSR increase by 13% from 1.01 to 1.14, while the number of detectable cysts increased from 4.3 to 7.7.

Feasibility study: real-time 3-D ultrasound imaging of the brain.

We tested the feasibility of real-time, 3-D ultrasound (US) imaging in the brain. The 3-D scanner uses a matrix phased-array transducer of 512 transmit channels and 256 receive channels operating at 2.5 MHz with a 15-mm diameter footprint. The real-time system scans a 65 degrees pyramid, producing up to 30 volumetric scans per second, and features up to five image planes as well as 3-D rendering, 3-D pulsed-wave and color Doppler. In a human subject, the real-time 3-D scans produced simultaneous transcranial horizontal (axial), coronal and sagittal image planes and real-time volume-rendered images of the gross anatomy of the brain. In a transcranial sheep model, we obtained real-time 3-D color flow Doppler scans and perfusion images using bolus injection of contrast agents into the internal carotid artery.

Clot retraction affects the extent of ultrasound-enhanced thrombolysis in an ex vivo porcine thrombosis model.

We investigated ultrasound-enhanced thrombolysis in two whole-blood clot models using a Food and Drug Administration-approved contrast agent (Definity, Lantheus Medical Imaging; Billerica, MA USA) and thrombolytic drug (recombinant tissue-type plasminogen activator [rt-PA]) (Genentech; South San Francisco, CA USA). Porcine venous blood was collected from donor hogs and coagulated in vials made of two different materials. This method produced clots with differing compositional properties, as determined by routine scanning electron microscopy and histology. Clots were deployed in an ex vivo porcine thrombosis model, and exposed to an intermittent ultrasound scheme previously developed to maximize stable cavitation while acoustic emissions were detected. Exposure to 3.15 µg/mL rt-PA promoted lysis in both clot models, compared with exposure to plasma alone. However, only unretracted clots experienced significant enhancement of thrombolysis in the presence of rt-PA, Definity, and ultrasound, compared with treatment with rt-PA. In these clots, microscopy revealed loose erythrocyte aggregates, a significantly less extensive fibrin network and a higher porosity, which may facilitate increased penetration of thrombolytics by cavitation.

Ultrasound-enhanced rt-PA thrombolysis in an ex vivo porcine carotid artery model.

Ultrasound is known to enhance recombinant tissue plasminogen activator (rt-PA) thrombolysis. In this study, occlusive porcine whole blood clots were placed in flowing plasma within living porcine carotid arteries. Ultrasonically induced stable cavitation was investigated as an adjuvant to rt-PA thrombolysis. Aged, retracted clots were exposed to plasma alone, plasma containing rt-PA (7.1 ± 3.8 µg/mL) or plasma with rt-PA and Definity® ultrasound contrast agent (0.79 ± 0.47 µL/mL) with and without 120-kHz continuous wave ultrasound at a peak-to-peak pressure amplitude of 0.44 MPa. An insonation scheme was formulated to promote and maximize stable cavitation activity by incorporating ultrasound quiescent periods that allowed for the inflow of Definity®-rich plasma. Cavitation was measured with a passive acoustic detector throughout thrombolytic treatment. Thrombolytic efficacy was measured by comparing clot mass before and after treatment. Average mass loss for clots exposed to rt-PA and Definity® without ultrasound (n = 7) was 34%, and with ultrasound (n = 6) was 83%, which constituted a significant difference (p < 0.0001). Without Definity® there was no thrombolytic enhancement by ultrasound exposure alone at this pressure amplitude (n = 5, p < 0.0001). In the low-oxygen environment of the ischemic artery, significant loss of endothelium occurred but no correlation was observed between arterial tissue damage and treatment type. Acoustic stable cavitation nucleated by an infusion of Definity® enhances rt-PA thrombolysis without apparent treatment-related damage in this ex vivo porcine carotid artery model.

Comparison of 3-D multi-lag cross- correlation and speckle brightness aberration correction algorithms on static and moving targets.

Phase correction has the potential to increase the image quality of 3-D ultrasound, especially transcranial ultrasound. We implemented and compared 2 algorithms for aberration correction, multi-lag cross-correlation and speckle brightness, using static and moving targets. We corrected three 75-ns rms electronic aberrators with full-width at half-maximum (FWHM) auto-correlation lengths of 1.35, 2.7, and 5.4 mm. Cross-correlation proved the better algorithm at 2.7 and 5.4 mm correlation lengths (P < 0.05). Static cross-correlation performed better than moving-target cross-correlation at the 2.7 mm correlation length (P < 0.05). Finally, we compared the static and moving-target cross-correlation on a flow phantom with a skull casting aberrator. Using signal from static targets, the correction resulted in an average contrast increase of 22.2%, compared with 13.2% using signal from moving targets. The contrast-to-noise ratio (CNR) increased by 20.5% and 12.8% using static and moving targets, respectively. Doppler signal strength increased by 5.6% and 4.9% for the static and moving-targets methods, respectively.

The ultrasound brain helmet: feasibility study of multiple simultaneous 3D scans of cerebral vasculature.

We describe early stage experiments to test the feasibility of an ultrasound brain helmet to produce multiple simultaneous real-time three-dimensional (3D) scans of the cerebral vasculature from temporal and suboccipital acoustic windows of the skull. The transducer hardware and software of the Volumetrics Medical Imaging (Durham, NC, USA) real-time 3D scanner were modified to support dual 2.5 MHz matrix arrays of 256 transmit elements and 128 receive elements which produce two simultaneous 64 degrees pyramidal scans. The real-time display format consists of two coronal B-mode images merged into a 128 degrees sector, two simultaneous parasagittal images merged into a 128 degrees x 64 degrees C-mode plane and a simultaneous 64 degrees axial image. Real-time 3D color Doppler scans from a skull phantom with latex blood vessel were obtained after contrast agent injection as a proof of concept. The long-term goal is to produce real-time 3D ultrasound images of the cerebral vasculature from a portable unit capable of internet transmission thus enabling interactive 3D imaging, remote diagnosis and earlier therapeutic intervention. We are motivated by the urgency for rapid diagnosis of stroke due to the short time window of effective therapeutic intervention.

Autonomous surgical robotics using 3-D ultrasound guidance: feasibility study.

The goal of this study was to test the feasibility of using a real-time 3D (RT3D) ultrasound scanner with a transthoracic matrix array transducer probe to guide an autonomous surgical robot. Employing a fiducial alignment mark on the transducer to orient the robot's frame of reference and using simple thresholding algorithms to segment the 3D images, we tested the accuracy of using the scanner to automatically direct a robot arm that touched two needle tips together within a water tank. RMS measurement error was 3.8% or 1.58 mm for an average path length of 41 mm. Using these same techniques, the autonomous robot also performed simulated needle biopsies of a cyst-like lesion in a tissue phantom. This feasibility study shows the potential for 3D ultrasound guidance of an autonomous surgical robot for simple interventional tasks, including lesion biopsy and foreign body removal.