Douglas L. Miller’s research while affiliated with University of Michigan and other places

A 2012 review of therapeutic ultrasound was published to educate researchers and physicians on potential applications and concerns for unintended bioeffects (doi: 10.7863/jum.2012.31.4.623 ). This review serves as an update to the parent article, highlighting advances in therapeutic ultrasound over the past 12 years. In addition to general mechanisms for bioeffects produced by therapeutic ultrasound, current applications, and the pre‐clinical and clinical stages are outlined. An overview is provided for image guidance methods to monitor and assess treatment progress. Finally, other topics relevant for the translation of therapeutic ultrasound are discussed, including computational modeling, tissue‐mimicking phantoms, and quality assurance protocols.

No PDF available ABSTRACT Knowledge of the bulk acoustic properties of human chest wall is useful in the development and study of cardiac and lung ultrasound exposimetry. However, few studies have been performed on human tissue, and there is a need for attenuation data relevant to clinical diagnostic ultrasound. In this study, we measured the bulk acoustic attenuation in unembalmed, never-frozen human chest wall samples, using a GE Vivid 7, clinical diagnostic ultrasound machine. B-mode ultrasound with frequencies from 1.6 to 5.0 MHz was transmitted through human chest wall tissue samples and compared to equivalent-source signals transmitted through normal saline. The recorded signals were analyzed to characterize the acoustic attenuation. Preliminary results based on 9 donors show that both chest wall morphology and bulk attenuation properties vary widely between individuals. Chest wall thicknesses ranged from 2 to 6 cm. The mean linear acoustic attenuation coefficients, across all samples, ranged from 1.1 dB/cm MHz at 1.6 MHz to 1.7 dB/cm MHz at 5.0 MHz, with a frequency-averaged standard deviation of 0.4 dB/cm MHz. Across all donors and frequency and power settings, linear acoustic attenuation coefficients ranged from 0.5 to 2.3 dB/cm MHz. Variation in thoracic exposure may result from variations in the chest wall composition and morphology between patients.

High-intensity focused ultrasound has been shown to drive fountains and atomization at liquid-gas and tissue-gas interfaces. Though these phenomena are not well studied for diagnostic ultrasound, they have been hypothesized to play a role in diagnostic ultrasound-induced pulmonary capillary hemorrhage (PCH). We demonstrate that push pulses used in diagnostic shear wave elastography (SWE) also cause fountaining and atomization at water-air and blood-air interfaces. A focused ultrasound transducer (SSI SL15-4), was aimed upward, through water, at an air interface. An SWE pulse sequence, including four push pulses (amplitude ≤ 8.6 MPa, pulse duration ≅ 650 ms, and center frequency ≅ 5.0 MHz), was initiated. The interface was photographed at 20k fps and four successive fountains were observed. Fountains heights up to 12 and 11 mm were observed for water and blood respectively and ejected water droplets traveled up to 30 cm above the surface. The spacing of the four fountains was measured to be the same as the spacing of four PCH areas observed on rat lungs exposed to the same pulse sequence. Concurrent studies should reveal the relative efficacy of PCH induction from SWE and normal pulse echo and Doppler imaging.

Diagnostic ultrasound can induce pulmonary capillary hemorrhage (PCH) in rats and other mammals. This phenomenon represents the only clearly demonstrated biological effect of (non-contrast enhanced) diagnostic ultrasound and thus presents a uniquely important safety issue. However, the physical mechanism responsible for PCH remains uncertain more than 25 y after its discovery. Experimental research has indicated that neither heating nor acoustic cavitation, the predominant mechanisms for bioeffects of ultrasound, is responsible for PCH. Furthermore, proposed theoretical mechanisms based on gas-body activation, on alveolar resonance and on impulsive generation of liquid droplets all appear unlikely to be responsible for PCH, owing to unrealistic model assumptions. Here, a simple model based on the acoustical radiation surface pressure (ARSP) at a tissue–air interface is hypothesized as the mechanism for PCH. The ARSP model seems to explain some features of PCH, including the approximate frequency independence of PCH thresholds and the dependence of thresholds on biological factors. However, ARSP evaluated for experimental threshold conditions appear to be too weak to fully account for stress failure of pulmonary capillaries, gauging by known stresses for injurious physiologic conditions. Furthermore, consideration of bulk properties of lung tissue suggests substantial transmission of ultrasound through the pleura, with reduced ARSP and potential involvement of additional mechanisms within the pulmonary interior. Although these recent findings advance our knowledge, only a full understanding of PCH mechanisms will allow development of science-based safety assurance for pulmonary ultrasound.

It is well known that mortality rates are pro-cyclical. In this paper, we attempt to understand why. We find little evidence that cyclical changes in individuals' own employment-related behavior drives the relationship; own-group employment rates are not systematically related to own-group mortality. Further, most additional deaths that occur when the economy is strong are among the elderly, particularly elderly women and those residing in nursing homes. We also demonstrate that staffing in nursing homes moves counter-cyclically. These findings suggest that cyclical fluctuations in the quality of health care may be a critical contributor to cyclical movements in mortality.

We consider statistical inference for regression when data are grouped into clusters, with regression model errors independent across clusters but correlated within clusters. Examples include data on individuals with clustering on village or region or other category such as industry, and state- year differences- in- differences studies with clustering on state. In such settings, default standard errors can greatly overstate estimator precision. Instead, if the number of clusters is large, statistical inference after OLS should be based on cluster- robust standard errors. We outline the basic method as well as many complications that can arise in practice. These include cluster- specifi c fi xed effects, few clusters, multiway clustering, and estimators other than OLS. © 2015 by the Board of Regents of the University of Wisconsin System.

Although lung hemorrhage (LH) remains the only bioeffect of non-contrast, diagnostic ultrasound (DUS) proven to occur in mammals, a fundamental understanding of DUS-induced LH remains lacking. We hypothesize that the fragile capillary beds near the lungs surface may rupture as a result of ultrasound-induced strains and viscous stresses. We perform simulations of DUS waves propagating in tissue (modeled as water) and impinging on a planar lung surface (modeled as air) with hemispherical divots representing individual capillaries (modeled as water). Experimental ultrasound pulse waveforms of frequencies 1.5–7.5 MHz are used for the simulation. A high-order accurate discontinuity-capturing scheme solves the two-dimensional, compressible Navier-Stokes equations to obtain velocities, pressures, stresses, strains, and displacements in the entire domain. The mechanics of the capillaries are studied for a range of US frequencies and amplitudes. Preliminary results indicate a strong dependence of the total strain on the capillary size relative to the wavelength.

Lung hemorrhage (LH) remains the only bioeffect of non-contrast, diagnostic ultrasound (DUS) proven to occur in mammals. While DUS for lung imaging is routine in critical care situations, a fundamental understanding of DUS-induced LH remains lacking. The objective of this study is to numerically simulate DUS-lung interaction to identify potential damage mechanisms, with an emphasis on shear. Experimentally relevant ultrasound waveforms of different frequencies and amplitudes propagate in tissue (modeled as water) and interact with the lung (modeled as air). Different length scales ranging from single capillaries to lung surface sizes are investigated. For the simulations, a high-order accurate discontinuity-capturing scheme solves the two-dimensional, compressible Navier-Stokes equations to obtain velocities, pressures, stresses and interface displacements in the entire domain. In agreement with theoretical acoustic approximations, small interface displacements are observed. At the lung surface, shear stresses indicative of high strains rates develop and are shown to increase nonlinearly with decreasing ratio of interface curvature to ultrasonic wavelength.

Abstract A system for scanning zebrafish embryos with diagnostic ultrasound was developed for research into possible biological effects during development. Two troughs for holding embryos were formed from agarose in a rectangular dish and separated by an ultrasound absorber. A 4.9 MHz linear array ultrasound probe was positioned to uniformly scan all the embryos at the bottom of one trough, with the other used for controls. Zebrafish embryos were scanned continuously from 10-24 h post fertilization (hpf ) during the segmentation period and gross morphological parameters were measured at 30 hpf, including viability, length, number of visible axons, and the progression of the lateral line primordium (LLP). Our initial tests were encumbered by the thermal effects of probe self-heating, which resulted in accelerated development of the zebrafish embryos. After subsequent optimization, our test revealed a significant retardation of primary motor axons and the migration of the LLP in embryos scanned with ultrasound, which indicated a potential for nonthermal effects on neuronal development. This diagnostic ultrasound exposure system is suitable for further investigation of possible subtle bioeffects, such as perturbation of neuronal migration.

In this paper we estimate the causal effects on child mortality from moving into less distressed neighborhood environments. We match mortality data covering the period from 1997 to 2009 with information on every child in public housing that applied for a housing voucher in Chicago in 1997 (N=11,680). Families were randomly assigned to the voucher wait list, and only some families were offered vouchers. The odds ratio for the effects of being offered a housing voucher on overall mortality rates is equal to 1.13 for all children (95% CI 0.73-1.70), 1.34 for boys (95% CI 0.85-2.05) and 0.21 for girls (95% CI 0.01-1.04).