Conditionally Increased Acoustic Pressures in Nonfetal Diagnostic Ultrasound Examinations Without Contrast Agents: A Preliminary Assessment

Abstract

The mechanical index (MI) has been used by the US Food and Drug Administration (FDA) since 1992 for regulatory decisions regarding the acoustic output of diagnostic ultrasound equipment. Its formula is based on predictions of acoustic cavitation under specific conditions. Since its implementation over 2 decades ago, new imaging modes have been developed that employ unique beam sequences exploiting higher-order acoustic phenomena, and, concurrently, studies of the bioeffects of ultrasound under a range of imaging scenarios have been conducted. In 2012, the American Institute of Ultrasound in Medicine Technical Standards Committee convened a working group of its Output Standards Subcommittee to examine and report on the potential risks and benefits of the use of conditionally increased acoustic pressures (CIP) under specific diagnostic imaging scenarios. The term "conditionally" is included to indicate that CIP would be considered on a per-patient basis for the duration required to obtain the necessary diagnostic information. This document is a result of that effort. In summary, a fundamental assumption in the MI calculation is the presence of a preexisting gas body. For tissues not known to contain preexisting gas bodies, based on theoretical predications and experimentally reported cavitation thresholds, we find this assumption to be invalid. We thus conclude that exceeding the recommended maximum MI level given in the FDA guidance could be warranted without concern for increased risk of cavitation in these tissues. However, there is limited literature assessing the potential clinical benefit of exceeding the MI guidelines in these tissues. The report proposes a 3-tiered approach for CIP that follows the model for employing elevated output in magnetic resonance imaging and concludes with summary recommendations to facilitate Institutional Review Board (IRB)-monitored clinical studies investigating CIP in specific tissues.

Figure 1

Theoretical thresholds for inertial cavitation of optimally sized air bubbles in materials with various viscoelastic properties for a threshold criterion of T_max = 5000 K. A, Thresholds calculated assuming pressure durations of 1 acoustic period. B, Normalized (by data from 1 acoustic period in A) thresholds for inertial cavitation in each material at a pulse length of 100 acoustic periods. Curves are the best fits of P_t = Bf_cⁿ to the numerical data for water (●) blood (○), heart (□), kidney (■), liver (▽), skeletal muscle (▲), and skin (+). The average value for n (the power of frequency) for the combined curves was 0.75.

Figure 2

Peak rarefactional pressure (p_r) values measured in water (x) and derated by: 0.3 dB cm⁻¹ MHz⁻¹ (x), and 0.5 dB cm⁻¹ MHz⁻¹ (x); p_r derated water measurements linearly extrapolated from small signal values ((−), see appendix A); p_r estimated using a grid of source pressure measurements in water and modeling nonlinear propagation using the 3D KZK model with numerical solution methods described previously (CH4-1 only) assuming propagation through water (■) and milk (■); as well as in situ p_r measurements made in an evaporated milk solution ((●), measured attenuation = 0.5 dB cm⁻¹ MHz⁻¹). Note that derating water values by 0.3 dB cm⁻¹ MHz⁻¹ provides reasonable agreement with the milk measurements (to within 20% for all transducers); however, derating water values by the actual measured attenuation of the milk (0.5 dB cm⁻¹ MHz⁻¹) leads to considerable underestimation of the milk measurements. Additionally, the linear extrapolation approach considerably overestimates the milk measurements for the higher frequency transducers, whereas the source pressure + nonlinear simulation approach (black squares and green squares, left plot) is in good agreement with the milk measurements. Each array transducer was focused with an F/2 lateral focal configuration concurrent with its fixed elevation focus.

Figure 3

Best estimates of in situ rarefactional pressure shown in Table 1. Triangles and circles indicate values for brain and all other tissues, respectively. Curves delineate pressures calculated for the maximum value of the MI in the FDA’s guidance for track 3 devices (solid curve, labeled MI = 1.9) and an effective mechanical index of 4.0 (dashed curve, labeled MIE = 4.0).

Figure 4

a (fundamental) and b (THI pulse inversion), The two sets of curves represent the simulated (full-wave propagation) spectral content from a typical curvilinear array [center frequency = 3.8 MHz (a), 3.0 MHz (b)] at 0 mm (top set) and then at 12 (or 8) cm of depth (bottom set) after propagating through an attenuating medium (0.5 dB cm⁻¹ MHz⁻¹, plus 1.3 dB cm⁻¹ MHz⁻¹ at skin line). For each set, the green (blue) line is the received signal spectra with 120-V transmit, and the pink (red) line is the received signal spectrum with 60-V transmit. The bandwidth difference between the depths is about 0.25 MHz for the fundamental and 1 MHz for the harmonic sequence. c and d, Corresponding peak value of the received pulse as a function of depth for the fundamental (c) and THI (d) cases. Assuming signals below −45 dB will not be detected, these images indicate that a 100% increase in transmit voltage leads to a 1.25-cm (12%, fundamental) and 2.25-cm (25%, THI) increase in depth of penetration. Data provided by Fujifilm SonoSite.

Figure 5

Left, Percentage of successful shear wave speed measurements (8 attempts/patient/energy level) as a function of transmit energy level (E = transmit voltage²/element impedance) from 22 patients with a range of liver fibrosis stages and BMIs (E = 4 mJ is typical for current commercial systems). Right, Shear wave displacement estimation noise level (jitter) in these sequences obtained using harmonic imaging as a function of MI level. Note the increased yield and decreased jitter levels associated with CIP in these data. Data provided from an ongoing IRB-approved study at Duke University.