Dependence of Boiling Histotripsy Treatment Efficiency on HIFU Frequency and Focal Pressure Levels

Boiling histotripsy (BH) is a high-intensity focused ultrasound (HIFU)–based method of mechanical tissue fractionation that utilizes millisecond-long bursts of HIFU shock waves to cause boiling at the focus in milliseconds. The subsequent interaction of the incoming shocks with the vapor bubble mechanically lyses surrounding tissue and cells. The acoustic parameter space for BH has been investigated previously and an inverse dependence between the HIFU frequency and the dimensions of a BH lesion has been observed. The primary goal of the present study was to investigate in more detail the ablation rate and reliability of BH in the frequency range relevant to treatment of deep abdominal tissue targets (1–2 MHz). The second goal was to investigate the effect of focal peak pressure levels and shock amplitude on BH lesion formation, given a constant duty factor, a constant ratio of the pulse duration to the time to reach boiling and a constant number of BH pulses. A custom-built 12-element sector array HIFU transducer with F-number = 1.05 was used in all experiments. BH pulses at 5 different frequencies (1, 1.2, 1.5, 1.7 and 1.9 MHz) were delivered to optically transparent polyacrylamide gel phantoms and ex vivo bovine liver and myocardium tissue to observe cavitation and boiling bubble activity with high-speed photography and B-mode ultrasound imaging, correspondingly. In gel phantoms, a cavitation bubble cloud was shown to form prefocally and to shield the focus in all exposures at 1 and 1.2 MHz and in the highest amplitude exposures at 1.5–1.7 MHz; shielding was not observed at 1.9 MHz. In ex vivo tissue, this shielding effect was observed in 25% of exposures when peak negative in situ pressure exceeded 10.2 MPa at 1 MHz and 14.5 MPa at 1.5 MHz. When shielding occurred, the exposures resulted in mild tissue disruption in the prefocal region, but not liquefaction. The dimensions of liquefied lesions followed the inverse proportionality trend with frequency; consequently, the frequency range of 1.2–1.5 MHz appeared to be preferable for BH exposures in terms of the compromise between the ablation rate and reliability. The lesion size was independent of the duration of the BH pulses (or the total “HIFU on” time), provided that the number of pulses was constant and boiling was induced within each pulse. Thus, the use of shorter (1 ms vs. 10 ms), higher amplitude BH pulses allowed up to 10-fold reduction in treatment time for a given duty factor.     

Effect of magnetite nanoparticle agglomerates on the destruction of tumor spheroids using high intensity focused ultrasound

Magnetite (Fe₃O₄) nanoparticle agglomerates have been shown to enhance the degree of inertial cavitation induced by high-intensity focused ultrasound (HIFU). To investigate the effect of these particles on the destruction of tumor spheroids using HIFU, HeLa spheroids were insonated in the presence and absence of magnetite nanoparticle agglomerates. The HIFU transducer was operated with a frequency of 1.1 MHz, pulse repetition frequency of 1.67 kHz, 5% and 50% duty cycles and peak negative focal pressure of 7.2 MPa for 10 s. The significant increase in the HIFU-induced inertial cavitation caused by the presence of magnetite particles at 50% duty cycle was sufficient to cause cell lysis and disintegrate the whole spheroid (p ≤ 0.001). This suggests that magnetite nanoparticle agglomerates can enhance the efficacy of HIFU in tumor ablation and other related therapies. (E-mail: nkhs2@cam.ac.uk)     

Temporal and Spatial Detection of HIFU-Induced Inertial and Hot-Vapor Cavitation with a Diagnostic Ultrasound System

The onset and presence of inertial cavitation and near-boiling temperatures in high-intensity focused ultrasound (HIFU) therapy have been identified as important indicators of energy deposition for therapy guidance. Passive cavitation detection is commonly used to detect bubble emissions, where a fixed-focus single-element acoustic transducer is typically used as a passive cavitation detector (PCD). This technique is suboptimal for clinical applications, because most PCD transducers are tightly focused and afford limited spatial coverage of the HIFU focal region. A Terason 2000 Ultrasound System was used as a PCD array to expand the spatial detection region for cavitation by operating in passive mode, obtaining the radiofrequency signals corresponding to each scan line and filtering the contribution from scattering of the HIFU signal harmonics. This approach allows for spatially resolved detection of both inertial and stable cavitation throughout the focal region. Measurements with the PCD array during sonication with a 1.1-MHz HIFU source in tissue phantoms were compared with single-element PCD and thermocouple sensing. Stable cavitation signals at the harmonics and superharmonics increased in a threshold fashion for temperatures >90°C, an effect attributed to high vapor pressure in the cavities. Incorporation of these detection techniques in a diagnostic ultrasound platform could result in a powerful tool for improving HIFU guidance and treatment. (E-mail: cfarny@bwh.harvard.edu)     

An Acoustic Backscatter-Based Method for Localization of Lesions Induced by High-Intensity Focused Ultrasound

Ultrasound B-mode visualization of lesions produced in soft tissues using high-intensity focused ultrasound (HIFU) has been shown to be challenging when there is no cavitation activity and, therefore, no hyperechogenecity in the focal region. We investigated a method for the visualization and localization of HIFU-induced lesions after HIFU delivery was complete based on the change in backscattered radio-frequency (RF) signals. A HIFU transducer was used with focal dimension of 8 mm by 2 mm working at 5 MHz. HIFU was applied at different intensities to produce lesions in ex vivo chicken breast, with or without the generation of hyperecho in B-mode images. We compared lesion locations obtained from our RF-processing method, from measurement of physical lesions after exposure and from the B-mode images, if exposures had resulted in hyperecho. The results showed that the RF amplitude decreased as a function of time immediately after stopping the HIFU exposure. The lesions were clearly visualized in two-dimensional (2-D) images of the decay rate of RF amplitude, no matter with or without hyperecho. In experiments with hyperecho, when comparing to physical lesion locations, there was no statistically significant difference in the localization accuracy between the RF-based and the hyperecho-based method (p = 0.76). In cases without hyperecho, the distance between RF-based locations and measured lesion locations was 3.37 ± 1.59 mm (mean ± standard deviation). The axial and lateral difference were 2.00 ± 2.31 mm and 0.85 ± 2.15 mm, respectively, and no statistically significant difference was found between lesion coordinates (axial: p = 0.37 and lateral: p = 0.15). We demonstrated the feasibility of our proposed RF-based method for the localization of HIFU-induced lesions immediately after HIFU treatment. Using the decay rate in RF amplitude as the signature of lesion formation, our method can detect lesion locations even without the appearance of hyperecho. (E-mail: xlzheng@u.washington.edu)     

Control of Acoustic Cavitation for Efficient Sonoporation with Phase-Shift Nanoemulsions

Acoustic cavitation can be used to temporarily disrupt cell membranes for intracellular delivery of large biomolecules. Termed sonoporation, the ability of this technique for efficient intracellular delivery (i.e., >50% of initial cell population showing uptake) while maintaining cell viability (i.e., >50% of initial cell population viable) has proven to be very difficult. Here, we report that phase-shift nanoemulsions (PSNEs) function as inertial cavitation nuclei for improvement of sonoporation efficiency. The interplay between ultrasound frequency, resultant microbubble dynamics and sonoporation efficiency was investigated experimentally. Acoustic emissions from individual microbubbles nucleated from PSNEs were captured using a broadband passive cavitation detector during and after acoustic droplet vaporization with short pulses of ultrasound at 1, 2.5 and 5 MHz. Time domain features of the passive cavitation detector signals were analyzed to estimate the maximum size (R_max) of the microbubbles using the Rayleigh collapse model. These results were then applied to sonoporation experiments to test if uptake efficiency is dependent on maximum microbubble size before inertial collapse. Results indicated that at the acoustic droplet vaporization threshold, R_max was approximately 61.7 ± 5.2, 24.9 ± 2.8, and 12.4 ± 2.1 μm at 1, 2.5 and 5 MHz, respectively. Sonoporation efficiency increased at higher frequencies, with efficiencies of 39.5 ± 13.7%, 46.6 ± 3.28% and 66.8 ± 5.5% at 1, 2.5 and 5 MHz, respectively. Excessive cellular damage was seen at lower frequencies because of the erosive effects of highly energetic inertial cavitation. These results highlight the importance of acoustic cavitation control in determining the outcome of sonoporation experiments. In addition, PSNEs may serve as tailorable inertial cavitation nuclei for other therapeutic ultrasound applications.     

A Study of Bubble Activity Generated in Ex Vivo Tissue by High Intensity Focused Ultrasound

Cancer treatment by extracorporeal high-intensity focused ultrasound (HIFU) is constrained by the time required to ablate clinically relevant tumour volumes. Although cavitation may be used to optimize HIFU treatments, its role during lesion formation is ambiguous. Clear differentiation is required between acoustic cavitation (noninertial and inertial) effects and bubble formation arising from two thermally-driven effects (the vapourization of liquid into vapour, and the exsolution of formerly dissolved permanent gas out of the liquid and into gas spaces). This study uses clinically relevant HIFU exposures in degassed water and ex vivo bovine liver to test a suite of cavitation detection techniques that exploit passive and active acoustics, audible emissions and the electrical drive power fluctuations. Exposure regimes for different cavitation activities (none, acoustic cavitation and, for ex vivo tissue only, acoustic cavitation plus thermally-driven gas space formation) were identified both in degassed water and in ex vivo liver using the detectable characteristic acoustic emissions. The detection system proved effective in both degassed water and tissue, but requires optimization for future clinical application. (E-mail: jmclaughlan7@gmail.com)     

The effects of continuous wave and pulsed ultrasound on rat thymocytes in vitro

Rat thymocytes in suspension were exposed to continuous wave and pulsed ultrasound at frequencies of 0.5 and 1 MHz. In qualitative confirmation of the observations of Chapman et al. (1979), cell lysis and cell survival were found to depend upon ultrasound intensity, frequency and time of exposure. Cell survival after 10 min, 2 W/cm², 0.5 MHz was approx. 40 percent of control. Pulsed exposures at 0.5 MHz with the same temporal average intensity but with a temporal peak intensity of 30 W/cm² showed no statistically significant decrease in survival in comparison with controls. The thymocyte observations provide no support for the belief that diagnostic ultrasound may cause biological effects in the fluids of the body.     

Non-invasive High-Intensity Focused Ultrasound Treatment of Liver Tissues in an In Vivo Porcine Model: Fast,Large and Safe Ablations Using a Toroidal Transducer

A toroidal high-intensity focused ultrasound (HIFU) transducer was used to non-invasively treat liver tissues in vivo in a pig model. The transducer was divided into 32 concentric rings with equal surface areas operating at 2.5 MHz. First, attenuation of skin, fat, muscle and liver tissues was measured in fresh animal samples to adjust the energy delivered to the focal zone. Then, 8 animals were included in the present protocol and placed in a dorsal decubitus proclive position at an angle of 15°. The device was held by hand, and sonications were performed during apnea. Two thermal HIFU lesions were created in 40 s in each animal. The average abdominal wall thickness was 14.8 ± 1.3 mm (12.5–17.6 mm). The longest and shortest axes of the HIFU ablations were 20.9 ± 6.3 mm (14.0–33.7 mm) and 14.2 ± 5.5 mm (7.0–22.0 mm), respectively. All HIFU lesions were visible on sonograms. The correlation between the dimensions of the HIFU lesions observed on sonograms and those obtained during gross examination was r = 0.84. Creating large and fast ablations with reliable ultrasound imaging guidance in the liver using this handheld device may represent a new therapeutic option for patients with liver tumors.     

Strongly Focused HIFU Transducers With Simultaneous Optical Observation for Treatment of Skin at 20 MHz

High-intensity focused ultrasound (HIFU) transducers are proposed as a new treatment modality for dermatology. The shape and size of pressure fields generated by strongly focused transducers with an f-number equal to 0.75 operating at frequencies up to 20 MHz are analyzed analytically using the Lucas–Muir model and numerically with the wide-angle Khokhlov–Zabolotskaya–Kuznetsov method. The modeling results under quasi-linear conditions are compared against measurements performed in an acoustic tank with the aid of a fiberoptic hydrophone. The size of the focal zone expressed by their depth of focus and focal diameter is found to be directly controlled by their operating frequency and f-number. Devices manufactured for an operating frequency of 20 MHz are characterized by their 6 dB depth of focus of 490 μm and focal diameter of 80.6 µm. The devices are further studied at high power levels using a polyacrylic tissue-mimicking phantom. The devices are equipped with an optical observation system allowing simultaneous treatment and observation of the skin surface. In comparison to conventional cosmetic applications of HIFU, the devices analyzed are concluded to be ideal for treatment of precisely selected and confined layers of the human skin.     

Cancer treatment using an optically inert Rose Bengal derivative combined with pulsed focused ultrasound

Pulsed high intensity focused ultrasound (HIFU) has been combined with a photo-insensitive Rose Bengal derivative (RB2) to provide a synergistic cytotoxicity requiring the presence of both ultrasonic cavitation and drug. In vitro tests have shown that a short treatment (less than 30 s) of pulsed HIFU with peak negative pressure > 7 MPa (~ 27 W acoustic power at 1.4 MHz) destroys > 95% of breast cancer cells MDA-MB-231 in suspension with > 10 μM of the compound. Neither the pulsed HIFU nor the RB2 compound was found to have any significant impact on the viability of the cells when used alone. Introducing an antioxidant (N-acetylcysteine) reduced the effectiveness of the treatment. In vivo tests using these same cells growing as a xenograft in nu/nu mice were also done. An ultrasound contrast agent (Optison) and lower frequency (1.0 MHz) was used to help initiate cavitation at the tumor site. We were able to demonstrate tumor regression with cavitation alone, however, addition of RB2 compound injected i.v. yielded a substantial synergistic improvement.     

Hyperecho in ultrasound images of HIFU therapy: involvement of cavitation

High-intensity focused ultrasound (US), or HIFU, treatment of soft tissues has been shown to result in a hyperechoic region in B-mode US images. We report on detecting cavitation in vivo in correlation with the appearance of a hyperechoic region. The US system consisted of a HIFU transducer (3.3 MHz), a broadband A-mode transducer for active and passive cavitation detection and an US-imaging probe that were all confocal and synchronized. HIFU, at in situ intensities of 220 to 1710 W/cm(2), was applied for 10 s to pig muscles in vivo. Active and passive cavitation detection results showed a strong correlation between the onset of cavitation and the appearance of a hyperechoic region. Passive cavitation detection results showed that inertial cavitation typically occurred prior (within 0.5 s) to the appearance of a hyperechoic region. The observed cavitation activity confirms that bubbles are present during the formation of a hyperechoic region at the HIFU focus.     

Attenuation and De-focusing During High-Intensity Focused Ultrasound Therapy Through Peri-nephric Fat

High-intensity focused ultrasound (HIFU) is an attractive therapy for kidney cancer, but its efficacy can be limited by heat deposition in the pre-focal tissues, notably in fat around the kidney (peri-nephric fat), the acoustic properties of which have not been well characterized. Measurements of attenuation were made using a modified insertion-loss technique on fresh, unfixed peri-nephric fat obtained from patients undergoing kidney surgery for cancer. The de-focusing effect of changing the position of the fat layers was also investigated using fresh subcutaneous fat from euthanized pigs. The mean attenuation of human peri-nephric fat was found to be 11.9 ± 0.9 Np/m (n = 10) at 0.8 MHz, the frequency typically used for HIFU ablation of kidney tumors, with a frequency dependence of f^1.2. A typical 2- to 4-cm thickness of peri-nephric fat would result in a de-rated intensity of 3%–62% at 0.8 MHz compared with a hypothetical patient with no peri-nephric fat. Through the use of freshly excised porcine subcutaneous fat, the presence of fat 100 mm in front of the focus was found to have a de-focusing effect of approximately 1 mm in both transverse directions, which corresponds to a full HIFU beam width off-target. Peri-nephric fat may significantly affect both the intensity and accuracy of HIFU fields used for the ablation of kidney cancer.     

The Destruction of Escherichia Coli Biofilms Using High-Intensity Focused Ultrasound

High-intensity focused ultrasound (HIFU) has shown great potential for replacing surgery in many applications. In this work, HIFU was used to destroy Escherichia coli (E. coli) biofilms that had been grown on chambered microscope slides. Biofilms are central to the pathogenesis and persistence of nosocomial (hospital-acquired) infections associated with indwelling medical devices. The slides were exposed to 9.1 μs pulses at a pulse repetition frequency of 1000 Hz. The pulses were generated by a 1.1 MHz spherically focused source with a focal length of 6.3 cm and an active diameter of 7 cm. The peak rarefactional pressure for the pulses was varied as 3.1, 4.1, 5.2, 6.2 and 7.6 MPa in addition to a sham where the biofilms were not exposed. The effectiveness of the treatment was assessed by determining the number of colony forming units (CFU) remaining following exposure of the bacteria to HIFU. Most of the biofilms treated at the higher exposures of 6.2 and 7.6 MPa had no detectable CFU, indicating that bacteria in the biofilm were killed by the treatment or that treatment disrupted the biofilm and released bacteria from the slide. However, the ability of some bacteria to survive at the higher exposure settings needs to be resolved prior to implementing the treatment clinically. (E-mail: bigelow@iastate.edu).     

Calibration of Ultrasound Backscatter Temperature Imaging for High-Intensity Focused Ultrasound Treatment Planning

High-intensity focused ultrasound (HIFU) is rapidly gaining acceptance as a non-invasive method for soft tissue tumor ablation, but improvements in the methods of treatment delivery, planning and monitoring are still required. Backscatter temperature imaging (BTI) uses ultrasound to visualize heating-induced echo strain and may be used to indicate the position of the HIFU focal region using low-power “sub-lesioning” exposure. The technique may also provide a quantitative tool for assessing the efficacy of treatment delivery if apparent strain measurements can be related to the underlying temperature rise. To obtain temperature estimates from strain measurements, the relationship between these variables has to be either measured or otherwise assumed from previous calibrations in similar tissues. This article describes experimental measurements aimed at deriving the relationship between temperature rise and apparent strain in the laboratory environment using both ex vivo bovine liver tissue samples and normothermically perfused porcine livers. A BTI algorithm was applied to radiofrequency ultrasound echo data acquired from a clinical ultrasound scanner (Z.One, Zonare Medical Systems, Mountain View, CA, USA) where the imaging probe was aligned with the focal region of a HIFU transducer. Temperature measurements were obtained using needle thermocouples implanted in the liver tissue. A series of “non-ablative” HIFU exposures giving peak temperatures below 10°C were made in three separate ex vivo bovine livers, yielding an average strain/temperature coefficient of 0.126 ± 0.088 percentage strain per degree Celsius. In the perfused porcine livers at a starting temperature of 38°C (normal body temperature) the strain/temperature coefficients were found to be 0.040 ± 0.029 percentage strain per degree Celsius. The uncertainty in these results is directly linked to the precision of the strain measurement, as well as the naturally occurring variance between different tissue samples, indicating that BTI may lack the accuracy required to be implemented successfully in practice as a quantitative treatment planning technique at a sub-lesioning exposure level. This is because, to be of use in treatment planning, temperature-rise estimates may require an accuracy greater (<10%) than that offered by BTI measurement. BTI may, however, still play a role in ensuring the correct positioning of the focal region and as a treatment monitoring modality capable of detecting an increased rate of heating in tissue after HIFU ablation.     

Passive Cavitation Detection during Pulsed HIFU Exposures of Ex Vivo Tissues and In Vivo Mouse Pancreatic Tumors

Pulsed high-intensity focused ultrasound (pHIFU) has been shown to enhance vascular permeability, disrupt tumor barriers and enhance drug penetration into tumor tissue through acoustic cavitation. Monitoring of cavitation activity during pHIFU treatments and knowing the ultrasound pressure levels sufficient to reliably induce cavitation in a given tissue are therefore very important. Here, three metrics of cavitation activity induced by pHIFU and evaluated by confocal passive cavitation detection were introduced: cavitation probability, cavitation persistence and the level of the broadband acoustic emissions. These metrics were used to characterize cavitation activity in several ex vivo tissue types (bovine tongue and liver and porcine adipose tissue and kidney) and gel phantoms (polyacrylamide and agarose) at varying peak-rare factional focal pressures (1–12 MPa) during the following pHIFU protocol: frequency 1.1 MHz, pulse duration 1 ms and pulse repetition frequency 1 Hz. To evaluate the relevance of the measurements in ex vivo tissue, cavitation metrics were also investigated and compared in the ex vivo and in vivo murine pancreatic tumors that develop spontaneously in transgenic KrasLSL.G12 D/+; p53 R172 H/+; PdxCretg/+ (KPC) mice and closely re-capitulate human disease in their morphology. The cavitation threshold, defined at 50% cavitation probability, was found to vary broadly among the investigated tissues (within 2.5–10 MPa), depending mostly on the water-lipid ratio that characterizes the tissue composition. Cavitation persistence and the intensity of broadband emissions depended both on tissue structure and lipid concentration. Both the cavitation threshold and broadband noise emission level were similar between ex vivo and in vivo pancreatic tumor tissue. The largest difference between in vivo and ex vivo settings was found in the pattern of cavitation occurrence throughout pHIFU exposure: it was sporadic in vivo, but it decreased rapidly and stopped over the first few pulses ex vivo. Cavitation activity depended on the interplay between the destruction and circulation of cavitation nuclei, which are not only used up by HIFU treatment but also replenished or carried away by circulation in vivo. These findings are important for treatment planning and optimization in pHIFU-induced drug delivery, in particular for pancreatic tumors.     

高强度聚焦超声对兔乳腺肿瘤急性损伤的研究

目的　应用高强度聚集超声(HIFU)对兔移植性乳腺肿瘤进行急性损伤研究。方法　以纯种荷瘤新西兰兔为实验对象,将1mm3VX2肿瘤组织块移植于兔乳腺组织内制作出VX2兔乳腺肿瘤动物模型。HIFU治疗探头频率为1.6MHz,焦域声强为5800W/cm2,连续超声波照射6s。结果　HIFU能准确地定位损伤靶区内兔乳腺肿瘤,其损伤程度为不可逆性。结论　实验结果表明HIFU能准确破坏乳腺肿瘤,为进一步开展临床研究提供了一定的实验依据     

An ex Vivo Human Lung Model for Ultrasound-Guided High-Intensity Focused Ultrasound Therapy Using Lung Flooding

The usability of an ex vivo human lung model for ablation of lung cancer tissue with high-intensity focused ultrasound (HIFU) is described. Lung lobes were flooded with saline, with no gas remaining after complete atelectasis. The tumor was delineated sono-morphologically. Speed of sound, tissue density and ultrasound attenuation were measured for flooded lung and different pulmonary cancer tissues. The acoustic impedance of lung cancer tissue (1.6–1.9 mega-Rayleighs) was higher than that of water, as was its attenuation coefficient (0.31–0.44 dB/cm/MHz) compared with that of the flooded lung (0.12 dB/cm/MHz). After application of HIFU, the temperature in centrally located lung cancer surrounded by the flooded lung increased as high as 80°C, which is sufficient for treatment. On the basis of these preliminary results, ultrasound-guided HIFU ablation of lung cancer, by lung flooding with saline, appears feasible and should be explored in future clinical studies.     

Microbubble-Enhanced Heating: Exploring the Effect of Microbubble Concentration and Pressure Amplitude on High-Intensity Focused Ultrasound Treatments

High-intensity focused ultrasound (HIFU) is a non-invasive tool that can be used for targeted thermal ablation treatments. Currently, HIFU is clinically approved for treatment of uterine fibroids, various cancers, and certain brain applications. However, for brain applications such as essential tremors, HIFU can only be used to treat limited areas confined to the center of the brain because of geometrical limitations (shape of the transducer and skull). A major obstacle to advancing this technology is the inability to treat non-central brain locations without causing damage to the skin and/or skull. Previous research has indicated that cavitation-induced bubbles or microbubble contrast agents can be used to enhance HIFU treatments by increasing ablation regions and shortening acoustic exposures at lower acoustic pressures. However, little research has been done to explore the interplay between microbubble concentration and pressure amplitude on HIFU treatments. We developed an in vitro experimental setup to study lesion formation at three different acoustic pressures and three microbubble concentrations. Real-time ultrasound imaging was integrated to monitor initial microbubble concentration and subsequent behavior during the HIFU treatments. Depending on the pressure used for the HIFU treatment, there was an optimal concentration of microbubbles that led to enhanced heating in the focal area. If the concentration of microbubbles was too high, the treatment was detrimentally affected because of non-linear attenuation by the pre-focal microbubbles. Additionally, the real-time ultrasound imaging provided a reliable method to monitor microbubble activity during the HIFU treatments, which is important for translation to in vivo HIFU applications with microbubbles.     

Experimental Measurements of Ultrasound Attenuation in Human Chest Wall and Assessment of the Mechanical Index for Lung Ultrasound

Knowledge of the acoustic attenuation characteristics of the chest wall is necessary to estimate the acoustic exposure at the pleural surface during lung ultrasound and is useful in the prediction of bio-effects (e.g., pulmonary capillary hemorrhage) and the development of safe, effective lung imaging. Currently, this property is not well characterized in humans. The aim of this work was to characterize ultrasonic attenuation in human chest wall such that the ultrasound exposures of the lung can be estimated for clinically relevant conditions. In this study, we experimentally measured ultrasound transmitted through the intercostal tissue of 15 human cadaver chest wall samples relative to ultrasound transmitted through saline to determine attenuation coefficients for each sample. A GE Vivid 7 diagnostic ultrasound machine (GE Vingmed, Horten, Norway) and 3 S and 5 S phased array probes were used at center frequencies from 1.6 to 5 MHz. The chest wall samples varied in thickness from 2.3–5.5 cm with a median thickness of 3.8 cm. The frequency-normalized attenuation coefficient was approximately 1.44 dB/cm/MHz based on a linear best fit through all attenuation measurements. Attenuation characteristics varied appreciably between samples, and the sample-averaged linear attenuation coefficient was 1.43 ± 0.32 (mean ± standard deviation) dB/cm/MHz. This attenuation is higher than that previously measured in mammalian chest wall samples (1.1–1.3 dB/cm/MHz for mice and rats) and is much greater than that used by the mechanical index (0.3 dB/cm/MHz). Mechanical index values calculated using saline values de-rated by 0.3 dB/cm/MHz were up to 1.2 MPa/MHz^1/2 greater than those calculated using the measured through-tissue ultrasound waves. We conclude that the mechanical index overestimates exposures for lung ultrasound and thus may not be an appropriate dosimetry metric for pulmonary ultrasound.