Remote acoustic sensing as a safety mechanism during exposure of metal implants to alternating magnetic fields

<div><p>Treatment of prosthetic joint infections often involves multiple surgeries and prolonged antibiotic administration, resulting in a significant burden to patients and the healthcare system. We are exploring a non-invasive method to eradicate biofilm on metal implants utilizing high-frequency alternating magnetic fields (AMF) which can achieve surface induction heating. Although proof-of-concept studies demonstrate the ability of AMF to eradicate biofilm in vitro, there is a legitimate safety concern related to the potential for thermal damage to surrounding tissues when considering heating implanted metal objects. The goal of this study was to explore the feasibility of detecting acoustic emissions associated with boiling at the interface between a metal implant and surrounding soft tissue as a wireless safety sensing mechanism. Acoustic emissions generated during in vitro and in vivo AMF exposures were captured with a hydrophone, and the relationship with surface temperature analyzed. The effect of AMF exposure power, surrounding media composition, implant location within the AMF transmitter, and implant geometry on acoustic detection during AMF therapy was also evaluated. Acoustic emissions were reliably identified in both tissue-mimicking phantom and mouse studies, and their onset coincided with the implant temperature reaching the boiling threshold. The viscosity of the surrounding medium did not impact the production of acoustic emissions; however, emissions were not present when the medium was oil due to the higher boiling point. Results of simulations and in vivo studies suggest that short-duration, high-power AMF exposures combined with acoustic sensing can be used to minimize the amount of thermal damage in surrounding tissues. These studies support the hypothesis that detection of boiling associated acoustic emissions at a metal/tissue interface could serve as a real-time, wireless safety indicator during AMF treatment of biofilm on metallic implants.</p></div

Time to boiling decreases with increasing AMF power in both tissue-mimicking phantom and in vivo.

<p>The red curve (squares) depicts the result for a ball embedded in a tissue-mimicking phantom, while the blue curve (triangles) depicts the result for the same ball embedded in the thigh muscle of mice. The relationship between time to boiling and power was similar for both experimental groups. Statistics: mean ± std (n = 4).</p

The influence of implant positioning within the coil on heating efficiency and time to boiling.

<p>(a) A diagram showing how a metal ball was moved in the axial and lateral direction from center towards the edge of the coil; (b) The relationship between the time to boiling and axial position; (c) The relationship between the time to boiling and lateral position. The experiments were conducted in low-viscosity hydrogel. Statistics: mean ± std (n = 3).</p

AMF exposures produce highly localized tissue damage in vivo.

<p>H&E-stained sections through the thighs of mice receiving AMF exposures. The cavity (CAV) represents the location of a surgically implanted 4.8 mm stainless steel ball. A sham-treated mouse (a) 7 days after surgical implantation shows a residual inflammatory response at the edge of the cavity. A mouse receiving a 190 W AMF exposure for 220 s (b) exhibits a rim of thermal damage surrounding the implant and extending approximately 3 mm from the cavity. The boundary between the damaged area and normal tissue is marked by a yellow-dashed line. A similar pattern of damage is seen for a mouse exposed to 800 W for 15 seconds (c), however the radial extent is only approximately 1.3 mm. A mouse after a 4300 W AMF exposure for 1.5 s (d) exhibits a circumferential pattern of damage extending to approximately 0.6 mm from the cavity rim. In all cases, the transition from damaged to normal muscle (dashed line in top panels) is abrupt. Scale bars represent 1 mm. To representatively show the details in the transition zone, a high-magnification image of the area indicated by a blue-dashed box in (c) was obtained and showed as the inset with the scale bar of 200 μm. (e-f) Numerical simulations of the mouse AMF exposures shows the relationship between AMF power, duration and thermal damage. The distance to the 240 CEM43 boundary (extent of irreversible thermal damage), the 80 CEM43 boundary (extent of reversible damage), and 16 CEM43 boundary (extent of initial bone damage) from the surface of the implanted metal ball are shown as a function of the time required to reach a surface temperature of 100°C on the ball. The construct of the 2D axisymmetric model is shown in e), while the trend for the damage contours is shown in f). The graph shows the rapidly reduced thermal damage distance as the time to boiling is decreased due to the increasing AMF power, indicating the enhanced safety of high power short AMF exposures. In addition, the distance between the black and red curves decreases as the time to boiling decreases, indicating a sharper thermal gradient in tissue for these exposures.</p

Comparison between H&E- and Masson’s trichrome-stained sections showing tissue thermal damage.

<p>A mouse 7 days after an 800 W AMF exposure lasting 4 seconds exhibits a circumferential pattern of damage in both (a) H&E staining and (b) Masson’s trichrome staining. In H&E-stained section (a), robust regenerative activity is seen at the edge of the thermal damage boundary (purple area). To representatively show the details, a high-magnification image of the area indicated by a blue-dashed box in was obtained and showed as the inset with the scale bar of 200 μm. In Masson’s trichrome-stained section (b), the blue area indicates necrotic muscle fibers, matching that seen in H&E-stained sections. (c,d) A mouse 7 days after a 4300 W AMF exposure shows similar findings. In all cases, the transition from damaged to normal muscle is abrupt and is best visualized on Masson’s trichrome stain. Scale bars represent 1 mm.</p

Boiling detection of a human-sized knee phantom.

<p>(a) A human-scale AMF system set up, including a human-sized knee implant, a customized coil which fits the knee size, and a hydrophone on top. (b) Sound signal during AMF-induction heating. The red dashed line indicates boiling signal detection threshold (0.001). The figure demonstrates that efficient heating on the human knee implant was achieved with the customized AMF system, and acoustic emissions related to boiling were successfully detected. Power: 4300 W.</p

Boiling detection and temperature characterization of ball bearing in different media.

<p>(a) tissue-mimicking phantom; (b) motor oil; hydrogel with viscosities of (c) 1 mm²/s and (d) 528 mm²/s. Similar boiling signal and temperature curve were observed in (a), (c) and (d). However, since the boiling point of oil is much higher than 100°C, boiling was not detected even when temperature of the ball bearing reached 160°C.</p

Frequency spectrum of the sound signals acquired from the hydrophone.

<p>(a) Frequency spectrum with no boiling occurrence in vivo (T<100°C, n = 3). The inset is the same data shown in the log scale. (b) Frequency spectrum at the onset of boiling (T = 100°C) both <i>in vivo</i> (n = 4) and in tissue-mimicking phantoms (n = 4); +: environmental noise. The figure shows that there are several consistent peaks between 0.4–1 kHz which are associated with boiling. These peaks were selected as boiling signatures and the area under curve (AUC) within 0.4–1 kHz was calculated to represent the sound signal strength. Statistics: mean ± std.</p

Relationship between temperature and AUC during AMF exposures of a ball bearing embedded in a tissue-mimicking phantom.

<p>The left y axis and blue curve represent the AUC of the acoustic signal and the right y axis and orange curve show the temperature of the ball. The green arrow indicates when a boiling signal was detected. The powers corresponding to (a)-(f) are 200, 250, 300, 400, 800, and 4300 W, respectively. The temperature was always approximately 100°C when boiling was detected. Furthermore, the time required to reach boiling significantly decreased with increasing power.</p

Boiling detection for implants with different geometry.

<p>(a) Ball; (b) Washer; and (c) Ring. The red dashed lines indicate the boiling signal detection threshold (0.003). Power utilized in the experiments: (a) 800, (b) 650, and (c) 650 W. The figure shows that boiling was detected for all implants irrespective of their geometry. The time to reach boiling was different however, due to the different heating efficiencies of each implant.</p