Experimental demonstration of passive acoustic imaging in the human skull cavity using CT-based aberration corrections

Abstract

Purpose: Experimentally verify a previously described technique for performing passive acoustic imaging through an intact human skull using noninvasive, computed tomography (CT)-based aberration corrections Jones et al. [Phys. Med. Biol. 58, 4981-5005 (2013)].

Methods: A sparse hemispherical receiver array (30 cm diameter) consisting of 128 piezoceramic discs (2.5 mm diameter, 612 kHz center frequency) was used to passively listen through ex vivo human skullcaps (n = 4) to acoustic emissions from a narrow-band fixed source (1 mm diameter, 516 kHz center frequency) and from ultrasound-stimulated (5 cycle bursts, 1 Hz pulse repetition frequency, estimated in situ peak negative pressure 0.11-0.33 MPa, 306 kHz driving frequency) Definity™ microbubbles flowing through a thin-walled tube phantom. Initial in vivo feasibility testing of the method was performed. The performance of the method was assessed through comparisons to images generated without skull corrections, with invasive source-based corrections, and with water-path control images.

Results: For source locations at least 25 mm from the inner skull surface, the modified reconstruction algorithm successfully restored a single focus within the skull cavity at a location within 1.25 mm from the true position of the narrow-band source. The results obtained from imaging single bubbles are in good agreement with numerical simulations of point source emitters and the authors' previous experimental measurements using source-based skull corrections O'Reilly et al. [IEEE Trans. Biomed. Eng. 61, 1285-1294 (2014)]. In a rat model, microbubble activity was mapped through an intact human skull at pressure levels below and above the threshold for focused ultrasound-induced blood-brain barrier opening. During bursts that led to coherent bubble activity, the location of maximum intensity in images generated with CT-based skull corrections was found to deviate by less than 1 mm, on average, from the position obtained using source-based corrections.

Conclusions: Taken together, these results demonstrate the feasibility of using the method to guide bubble-mediated ultrasound therapies in the brain. The technique may also have application in ultrasound-based cerebral angiography.

FIG. 1.

(a) Receiver element distribution. (b) Experimental setup.

FIG. 2.

Coronal and sagittal views of the hemispherical array, inner and outer skull surfaces, and source locations investigated for each of the specimens used in this study. The black x’s (circles) indicate locations investigated in the fixed source (tube phantom) experiments.

FIG. 3.

(a) Illustration of source- and CT-based skull aberration calculations at the array’s geometric focus for Skull B. Measured and simulated signals (f = 516 kHz) captured with and without the skull in place are shown for one receiver element (top row), along with the delayed skull signals (middle row). Envelopes of the aligned signals are shown (bottom row) to demonstrate amplitude correction calculation. (b) Skull amplitude and delay terms for the entire 128-element array. The vertical black line indicates the receiver chosen for the plots in (a).

FIG. 4.

Contour images of the fixed source emitter located at the array’s geometric focus, reconstructed in water, through a human skullcap (Skull C) without skull corrections, with source-based skull delay corrections, and CT-based skull delay corrections. Lateral (Z = 0) and axial (Y = 0) reconstructions are shown. The peak intensity (I_max) for each image is given normalized to the water control case at [0,0,0]. Linear contours are displayed at 10% intervals.

FIG. 5.

Contour images of the fixed source emitter located at [0,0,0], [20,0,0], and [40,0,0] mm. Reconstructions in water and through a human skullcap (Skull C) with source-based and CT-based skull delay corrections. Lateral (Z = 0) reconstructions are shown. The peak intensity (I_max) for each image is given normalized to the water control case at [0,0,0]. Linear contours are displayed at 10% intervals.

FIG. 6.

Image SNR as a function of fixed source location. (a) Results from transcranial (Skull C) reconstructions without skull corrections, with source-based and CT-based skull corrections, and water-path control reconstructions. (b) Results from transcranial (Skull C) reconstructions without skull corrections, with skull delay corrections (source- and CT-based) calculated from a single point (chosen to be [0,0,0]), and with location-specific skull delay corrections (source- and CT-based), as presented in (a).

FIG. 7.

Summary of the results from all fixed source experiments. The (a) positional error, (b) −3 dB volume, (c) peak sidelobe ratio, and (d) image SNR are plotted (averaged over 62 locations tested at least 25 mm from the inner skull surface, error bars denote one standard deviation) for each transcranial reconstruction case and for the water-path control case. Results for each skullcap investigated are shown, along with a mean value across all skulls.

FIG. 8.

Normalized maximum pixel projection images of the tube phantom, obtained through a human skullcap (Skull B), generated by electronically scanning the transmit focus (grid dimensions: 20 × 5 × 12 mm³; step size: 0.5 mm in X, 1 mm in Y, and 4 mm in Z). Transcranial images formed without skull corrections (n_frames = 9), with source-based skull delay corrections (n_frames = 238), and CT-based (n_frames = 194) skull delay corrections are shown. The cross sectional images (bottom row) were generated by taking the maximum pixel projection within the range of [−1,1] mm in X.

FIG. 9.

(a) Normalized intensity profiles along the X, Y, and Z directions for a single bubble located near the array’s geometric focus. Transcranial (Skull B) reconstructions with CT- and source-based skull delay corrections are shown. (b) Image quality metrics [full width at half maximum (FWHM), peak sidelobe ratio, image SNR] averaged over ten bubbles are plotted for measured (CT- and source-based skull delay corrections) and simulated data. Error bars denote one standard deviation.

FIG. 10.

(a) Maps of microbubble activity generated in a rat model through an ex vivo human skullcap (Skull B) during FUS exposure at pressure levels below (location 1; estimated in situ pressure = 0.24 MPa) and above (location 2; 0.33 MPa) the threshold for BBB opening. Lateral planes of maximum intensity are shown for reconstructions with no skull corrections and with source- and CT-based skull delay corrections. Linear contours are displayed at 10% intervals. (b) Contrast-enhanced T₁-weighted (CE-T1W) MR image of the same rat postsonication showing enhancement at sonication location 2. The sonication direction is into the page.