Superharmonic and Microultrasound Imaging With Plane Wave Beamforming Techniques

Abstract

Superharmonic contrast imaging (SpHI) suppresses tissue clutter and allows high-contrast visualization of the vasculature. An array-based dual-frequency (DF) probe has been developed for SpHI, integrating a 21-MHz, 256-element microultrasound imaging array with a 2-MHz, 32-element array to take advantage of the broadband nonlinear responses from microbubble (MB) contrast agents. In this work, ultrafast imaging with plane waves was implemented for SpHI to increase the acquisition frame rate. Ultrafast imaging was also implemented for microultrasound B-mode imaging (HFPW B-mode) to enable high-resolution visualization of the tissue structure. Coherent compounding was demonstrated in vitro and in vivo in both imaging modes. Acquisition frame rates of 4.5 kHz and 187 Hz in HFPW B-mode imaging were achieved for imaging up to 21 mm with one and 25 angles, respectively, and 3.5 kHz and 396 Hz in the SpHI mode with one and nine coherently compounded angles, respectively. SpHI images showed suppression of tissue clutter prior to and after the introduction of MBs in vitro and in vivo. The nine-angle coherently compounded 2-D SpHI images of contrast-filled flow channel showed a contrast-to-tissue ratio (CTR) of 26.0 dB, a 2.5-dB improvement relative to images reconstructed from 0° steering. Consistent with in vitro imaging, the nine-angle compounded 2-D SpHI of a Lewis lung cancer tumor showed a 2.6-dB improvement in contrast enhancement, relative to 0° steering, and additionally revealed a region of nonviable tissue. The 3-D display of the volumetric SpHI data acquired from a xenograft mouse tumor using both 0° steering and nine-angle compounding allowed the visualization of the tumor vasculature. A small vessel visible in the compounded SpHI image, measuring around [Formula: see text], is not visualized in the 0° steering SpHI image, demonstrating the superiority of the latter in detecting fine structures within the tumor.

Fig. 1.

Schematics of (a) the experimental setup using two VevoF2 programmable beamforming systems for controlling the high-frequency and low-frequency arrays of the dual-frequency probe used in superharmonic imaging and micro-ultrasound imaging; (b) setup for pressure profile and wavefront measurements; (c) in vitro flow channel phantom imaging and (d) in vivo mouse tumor imaging. A mechanical translation motor system was used in (d) to acquire volumetric data.

Fig. 2.

Schematics showing the pulse sequences used in (a) superharmonic imaging using the dual-frequency probe with the entire 32-element in the active transmit aperture (green) and the 4 successively active HF receive sub-apertures (blue) each consisting of 64 HF elements; and (b) micro-ultrasound B-mode imaging using the high-frequency array alone with plane wave beams. 3 HF transmit sub-apertures (green) consisting of 128 elements are successively active on transmit, while 6 HF sub-apertures (blue) of 64 elements are successively active on receive. HF receive sub-apertures are numbered chronologically. (c) Relevant parameters used in the calculation of the round-trip time-of-flight for beamforming for a Tx beam steered at an angle of $\theta$.

Fig. 3.

Measured pressure fields of plane wave beams transmitted from the 2 MHz linear array for two representative angles of (a) −10° and (b) 0° and displayed with 20 dB dynamic range after normalizing to the peak pressure (227.5 kPa) found at 0° as marked by the black cross in (b). Contour at −6 dB (purple) below the peak pressure at 0° are overlaid. Measured wavefronts of the two beams at 10 mm depth below the probe surface are shown in (c) at −10° steering and (d) at 0°. A red dashed line was plotted at 6.7 μs, corresponding to 10 mm depth, to show the tilt of the wavefront. (e) Pressure magnitudes measured laterally at 10 mm depth and on-axis for all 9 steering angles, as shown by the yellow dashed lines on (a) and (b). Pressure magnitudes were normalized to the peak on-axis pressures found at each steering angle. (f) The measured on-axis pressure of the LF waveform at 10 mm depth (blue) and its frequency spectrum (black) were plotted. The pressure peak positives and negative (magenta), as well as the peak frequency (black) were indicated with the markers (filled circles).

Fig. 4.

Measured pressure fields of plane wave beams transmitted from the 21 MHz linear array for two representative angles of (a) −11.76° and (b) 0° and displayed with 20 dB dynamic range after normalizing to the peak pressure (1.9 MPa) found at 0° as marked by the black cross in (b). Contours at −6 dB from the peak pressure at 0° are overlaid in purple. The plane wave beams were generated using elements #65 to #192 (middle 128 elements). Measured wavefronts of the two beams at 10 mm depth below the probe surface are shown in (c) at −11.76° steering and (d) at 0°. A red dashed line was plotted at 6.8 μs, corresponding to 10 mm depth, to show the tilt of the wavefront. (e) Pressure magnitudes measured at 10 mm depth for all 25 steering angles. Pressure magnitudes were normalized to the peak pressure (1.6 MPa) found at 10 mm depth at 0°.

Fig. 5.

Acoustic pressure profiles of plane wave beams transmitted from the three active apertures of the HF array (left: elements 1–128; middle: 65–192; right: 129–256) at 10 mm depth with (a) 0° and (b) 11.76° steering; and at 30 mm depth with (c) 0° and (d) 11.76° steering. Pressures at each depth were normalized to the peak pressure at 0° transmit. Red dashed boxes indicate low pressure transmitted from left and right apertures. Yellow shaded areas (−2.9 to 2.9 mm) indicate regions requiring wave transmission from the middle aperture.

Fig. 6.

Reconstructed images from SpHI of sparsely distributed MBs in water (a) at 0° LF transmit steering and (b) with 9-angle compounding. Insets at bottom left show an enlarged region containing a single MB. Signal envelopes are normalized to the peak MB signal found in each imaging mode. Lateral and axial FWHMs of individual MBs found over 50 frames are shown as scatter plots in (c) and (d) for 0° LF transmit steering and with 9-angle compounding, respectively. Mean and standard errors of lateral and axial FWHMs are computed for MBs located within the same 1 mm depth range, starting from 2–3 mm to 24–25 mm. Values for each depth range are plotted at midpoints (e.g. 2.5 mm for depth range 2–3 mm). The theoretical one-way lateral FWHM of the Rx aperture (20 MHz; f-number = 1.5) is plotted as a dashed line.

Fig. 7.

Superharmonic contrast imaging and HFPW imaging of a flow channel phantom filled with water and MBs. From top to bottom, SpHI using a walking aperture, with 0° plane wave, and coherently compounded from 9-angles of Tx beam steering, then HFPW imaging with 0° plane wave, and coherently compounding using 25 Tx angles. Images are normalized to the peak MB signal found on MB-filled channel in each imaging mode. All images are displayed with a −50 dB dynamic range. Image axes are in millimeters. A ROI used for CTR computation (green) is shown on the water-filled channel image in line-by-line SpHI.

Fig. 8.

Superharmonic contrast imaging and HFPW imaging of a subcutaneous Lewis lung cancer tumor (top row) prior to and (bottom row) after MB injection. From left to right, SpHI using a walking aperture, with 0° plane wave, and coherently compounded from 9-angles of Tx beam steering, then HFPW imaging with 0° plane wave, and coherently compounding using 25 Tx angles. Each image pair is normalized to its mean noise levels outside the tumor region (ROI #1). Displayed dynamic range is from 3 dB below the noise floor to the peak MB signal in each image pair to show the contrast enhancement. Image axes are in millimeters; a 3-mm scale bar is shown. Image artifacts are indicated with arrow heads. ROIs used for mean contrast enhancement computation (yellow) are shown for vascularized regions.

Fig. 9.

(a) Volume rendered superharmonic contrast images of a subcutaneous breast cancer tumor xenograft. Images acquired with (left) 0° transmit (right) 9-angle coherent compounding both (top) prior to and (bottom) after injection of the MB contrast agent. The tumor volume is delineated with a dashed line. Scale bars along the 3 orthogonal axes shown at the bottom right represent 1 mm. Representative fine structures are indicated by arrowheads. Image artifacts due to air bubbles in the ultrasound gel are visible. (b) 9-Angle coherently compounded 2D SpHI images of the same tumor post-injection at two representative motor locations that are −2 and +2 mm away from the central position. Images are normalized to the peak signal enveloped found at each motor position.