Acoustic properties across the human skull

Abstract

Transcranial ultrasound is emerging as a noninvasive tool for targeted treatments of brain disorders. Transcranial ultrasound has been used for remotely mediated surgeries, transient opening of the blood-brain barrier, local drug delivery, and neuromodulation. However, all applications have been limited by the severe attenuation and phase distortion of ultrasound by the skull. Here, we characterized the dependence of the aberrations on specific anatomical segments of the skull. In particular, we measured ultrasound propagation properties throughout the perimeter of intact human skulls at 500 kHz. We found that the parietal bone provides substantially higher transmission (average pressure transmission 31 ± 7%) and smaller phase distortion (242 ± 44 degrees) than frontal (13 ± 2%, 425 ± 47 degrees) and occipital bone regions (16 ± 4%, 416 ± 35 degrees). In addition, we found that across skull regions, transmission strongly anti-correlated (R=-0.79) and phase distortion correlated (R=0.85) with skull thickness. This information guides the design, positioning, and skull correction functionality of next-generation devices for effective, safe, and reproducible transcranial focused ultrasound therapies.

Keywords: Attenuation; Phase; Skull; Thickness; Transcranial ultrasound; Transmission.

Figure 1:. Through-transmit measurements across intact skulls.

(a) Top view of the setup. Degassed and hydrated ex-vivo skulls were held by a robotic arm and were secured to the skull using two opposing magnets positioned at the center of the sagittal suture (the thin circle shows the position of the magnets). This robotic arm, connected to the magnet at the top of the skull, allowed us to electronically rotate the skull and so collect through-transmit measurements over individual segments of the skull within the imaging plane. The through-transmit measurements were achieved using a transmitting (Tx) and a receiving (Rx) transducer facing each other at a distance of 100 mm. The direction of ultrasound transmission is indicated by the dashed arrow. The through-transmit measurements were acquired at each rotation step of 1 degree. (b) Parameterization of the skull bone into parietal (45–135 and 225–315 degrees), occipital (135–225 degrees), and frontal (315–45 degrees) regions.

Figure 2:. Subjects.

CT scans for the three ex-vivo skulls used in this study. The images were taken at the through-transmit plane.

Figure 3:. Ultrasound transmission throughout the skull.

The figure shows the relative pressure attenuation (skull versus no skull) for each measured segment of the skull. The carrier frequency was 500 kHz.

Figure 4:. Skull thickness across angular position.

Mean thickness of each segment of the skull within the through-transmit plane. Three independent measurements were taken at each position.

Figure 5:. Ultrasound transmission is strongly governed by skull thickness.

Ultrasound pressure transmission (top) and its natural logarithm (bottom) as a function of skull thickness. The R² values listed in the inset provide the amount of variance explained by the linear fits superimposed on the plots.

Figure 6:. Speedup and phase distortion across the skull.

Ultrasound speedup through the skull (τ) and the associated phase distortion (ωτ) as a function of the skull position. Several segments of the occipital and frontal bones in Skull 2 provided extreme aberration, rendering the through-transmit cross-correlation unreliable; values for these segments are therefore not shown.

Figure 7:. Ultrasound phase distortion is proportional to skull thickness.

Ultrasound speedup through individual segments of the skull as a function of skull thickness. The R² values listed in the inset provide the amount of variance explained by the linear fits superimposed on the plots.

Figure 8:. Speed of sound across the skull.

The speed of sound (c_s) determined from the through-transmit τ values (see Materials and Methods) as a function of the skull position.

Figure 9:. Intensity attenuation factor distribution by skull section.

Intensity attenuation factor (T⁻²) varies significantly by region of the skull. The parietal bone’s 5^th to 95^th percentile range is an order of magnitude lower than both the frontal and occipital regions.