Brian MacConaghy

A mechanistic analysis of stone fracture in lithotripsy

In vitro experiments and an elastic wave model were used to analyze how stress is induced in kidney stones by lithotripsy and to test the roles of individual mechanisms-spallation, squeezing, and cavitation. Cylindrical U30 cement stones were treated in an HM-3-style lithotripter. Baffles were used to block specific waves responsible for spallation or squeezing. Stones with and without surface cracks added to simulate cavitation damage were tested in glycerol (a cavitation suppressive medium). Each case was simulated using the elasticity equations for an isotropic medium. The calculated location of maximum stress compared well with the experimental observations of where stones fractured in two pieces. Higher calculated maximum tensile stress correlated with fewer shock waves required for fracture. The highest calculated tensile stresses resulted from shear waves initiated at the proximal corners and strengthened along the side surfaces of the stone by the liquid-borne lithotripter shock wave. Peak tensile stress was in the distal end of the stone where fracture occurred. Reflection of the longitudinal wave from the distal face of the stone--spallation-produced lower stresses. Surface cracks accelerated fragmentation when created near the location where the maximum stress was predicted.

Vibro‐acoustography for targeting kidney stones during lithotripsy

Vibro‐acoustography can be used to measure material properties and detect calcifications within the body. Two transducers (diameter 10 cm, curvature 20 cm, frequency 1.1 MHz) are placed with overlapping foci in degassed water and driven at different frequencies to produce a dynamic radiation force in the range of 5–50 kHz. A LabVIEW program instructs the transducers to sweep through this frequency range at 500‐Hz increments while a synthetic cylindrical kidney stone is held in the focus in one of three ways: with a rubber band, within an acrylamide gel, or within a finger cot. A low‐frequency hydrophone, 10 cm from the focus and 90 deg from the direction of propagation, detects the radiated acoustic emission from the stone. The average amplitude of five signals is recorded to measure the frequency response of the stone. Unbroken stones exhibited higher amplitude response at frequencies near 10, 25, and 35 kHz. Stones are moved to simulate patient breathing and different in‐focus and out‐of‐focus acoustic ...

Ultrasound stylet for non-image-guided ventricular catheterization.

OBJECT Urgent ventriculostomy placement can be a lifesaving procedure in the setting of hydrocephalus or elevated intracranial pressure. While external ventricular drain (EVD) insertion is common, there remains a high rate of suboptimal drain placement. Here, the authors seek to demonstrate the feasibility of an ultrasound-based guidance system that can be inserted into an existing EVD catheter to provide a linear ultrasound trace that guides the user toward the ventricle. METHODS The ultrasound stylet was constructed as a thin metal tube, with dimensions equivalent to standard catheter stylets, bearing a single-element, ceramic ultrasound transducer at the tip. Ultrasound backscatter signals from the porcine ventricle were processed by custom electronics to offer real-time information about ventricular location relative to the catheter. Data collected from the prototype device were compared with reference measurements obtained using standard clinical ultrasound imaging. RESULTS A study of porcine ventricular catheterization using the experimental device yielded a high rate of successful catheter placement after a single pass (10 of 12 trials), despite the small size of pig ventricles and the lack of prior instruction on porcine ventricular architecture. A characteristic double-peak signal was identified, which originated from ultrasound reflections off of the near and far ventricular walls. Ventricular dimensions, as obtained from the width between peaks, were in agreement with standard ultrasound reference measurements (p < 0.05). Furthermore, linear ultrasound backscatter data permitted in situ measurement of the stylet distance to the ventricular wall (p < 0.05), which assisted in catheter guidance. CONCLUSIONS The authors have demonstrated the ability of the prototype ultrasound stylet to guide ventricular access in the porcine brain. The alternative design of the device makes it potentially easy to integrate into the standard workflow for bedside EVD placement. The availability of a fast, easy-to-use, inexpensive guidance system can play a role in reducing the complication rate for EVD placement.

Measurement of reduced stress in model kidney stones with increased rate of shock wave delivery in lithotripsy

Slow clinical shock wave rates more effectively comminute stones. Higher rates create more cavitation bubbles along the focusing axis. Bubble clouds potentially reflect or attenuate the shock wave and also may collapse less energetically. Here, high‐speed photo‐elastography was used to visualize the dynamic stress distribution inside a transparent model stone. Photo‐elastography records constant‐stress lines, making quantification possible. PVDF sensors (4 mm diameter) measured force on the proximal face of the stones. The impulsive force of the shock wave and the cloud collapse at various clinical rates (single shocks, 1 Hz, 2 Hz, 3 Hz) in degassed and non‐degassed water were calculated from the measurements. Impulse forces from the shock wave and cavitation collapse were comparable in the range 4−7×10−4 Ns. At clinical rates in gas‐saturated water, the stress fringes of the tensile component of the shock wave were reduced; the observable maximum stress was decreased; and impulsive force from the shock a...

Ultrasound-based cell sorting with microbubbles: A feasibility study

The isolation and sorting of cells is an important process in research and hospital labs. Most large research and commercial labs incorporate fluorescently or magnetically labeled antibodies adherent to cell surface antigens for cell identification and separation. In this paper, a process is described that merges biochemical labeling with ultrasound-based separation. Instead of lasers and fluorophore tags, or magnets and magnetic particle tags, the technique uses ultrasound and microbubble tags. Streptavidin-labeled microbubbles were mixed with a human acute lymphoblastic leukemia cell line, CCL 119, conjugated with biotinylated anti-CD7 antibodies. Tagged cells were forced under ultrasound, and their displacement and velocity quantified. Differential displacement in a flow stream was quantified against erythrocytes, which showed almost no displacement under ultrasound. A model for the acoustic radiation force on the conjugated pairs compares favorably with observations. This technology may improve on current time-consuming and costly purification procedures.

Generation of guided waves during burst wave lithotripsy as a mechanism of stone fracture

Burst wave lithotripsy (BWL) is an experimental method to noninvasively fragment urinary stones by short pulses of focused ultrasound. We are investigating physical mechanisms of stone fracture during BWL to better optimize this procedure. In this study, we used photoelasticity imaging as a method to visualize elastic wave dynamics in model stones. Epoxy and glass stone models were made into cylindrical, rectangular, or irregular geometries and exposed in a degassed water bath to focused ultrasound bursts at different frequencies. A high-speed camera was used to record images of the stone during exposure through a circular polariscope backlit by a monochromic flash source. Results showed development of periodic stresses in the stone body with a pattern dependent on frequency. These were identified as guided wave modes in cylinders and plates, which formed standing waves upon reflection from the distal surfaces of the stone model, causing periodic stress positions. Measured phase velocities compared favorably to specific numerically calculated modes dependent on frequency and material. Artificial stones exposed to BWL produced cracks at positions anticipated by this mechanism. These results support guided wave production and reflection as a mechanism of stone fracture in BWL. [Work supported by K01 DK104854 and P01 DK043881.] Burst wave lithotripsy (BWL) is an experimental method to noninvasively fragment urinary stones by short pulses of focused ultrasound. We are investigating physical mechanisms of stone fracture during BWL to better optimize this procedure. In this study, we used photoelasticity imaging as a method to visualize elastic wave dynamics in model stones. Epoxy and glass stone models were made into cylindrical, rectangular, or irregular geometries and exposed in a degassed water bath to focused ultrasound bursts at different frequencies. A high-speed camera was used to record images of the stone during exposure through a circular polariscope backlit by a monochromic flash source. Results showed development of periodic stresses in the stone body with a pattern dependent on frequency. These were identified as guided wave modes in cylinders and plates, which formed standing waves upon reflection from the distal surfaces of the stone model, causing periodic stress positions. Measured phase velocities compared favora...

Toward detection of early apoptosis using labeled microbubbles

Chemotherapy is useful for treating metastases, but on average only 50% of tumors respond to the initial choice of drug(s). Many patients thus suffer from unnecessary side effects while their tumors continue to grow, until the proper drugs are found. Because most drugs kill cancer cells by inducing apoptosis, detection of apoptosis can be used to assess drug efficacy prior to treatment. Current technologies require large cell numbers and several time points for quantification. We propose a simple drug screening tool to monitor early apoptosis using annexin-V labeled microbubbles. We investigated the parameter space for such a tool with a transparent flow chamber such that the acoustic radiation force would be relatively parallel with the focal plane of the microscope’s objective. An uncalibrated PZT was activated with a small voltage from a function generator (1-10 V, 2 MHz), generating sufficient pressure to displace microbubble-labeled cells. Initial studies focused on detection of labeled leukemia cell...

Broad beam for more effective ultrasonic propulsion of kidney stones

Ultrasonic propulsion uses focused bursts of ultrasound to generate radiation force to non-invasively reposition stones. Ultrasonic propulsion has been implemented on a C5-2 curvilinear array and shown to be safe and effective for expelling small stones and fragments in a human feasibility study. Here, we evaluated the efficacy of three different focal beam patterns in moving stones: 1) the existing approach exciting all 128 elements of the C5-2 transducer at 2 MHz, 2) exciting only 40 elements, and 3) implementing a separate single element transducer at 350 kHz. The capability of each method to lift clusters of 1-2 mm and 3-4 mm calcium oxalate stone fragments in a pipette was measured, filmed and compared by calculating the sum of the product of fragment area and distance moved for all fragments. For the same peak pressure, the alternative approaches (2 and 3) lifted greater stone mass than the original output. With 1-2 mm fragments, improvement with the three methods was 14% and 500%. For 3-4 mm, impro...

Design of transmission-mode measurements for estimating ultrasound attenuation and nonlinearity in liver

Previously, it has been shown that ultrasound measurements of sound speed and nonlinearity can be used to quantify the fatty and non-fatty components of liver tissue. In addition, it has been proposed that ultrasound attenuation measurements can be used to distinguish fatty components comprising either sub-micron lipid droplets (microsteatosis) or much larger cell-sized droplets (macrosteatosis). To perform all of these measurements, a caliper device is being developed based on a transmission-mode approach. Design challenges are posed by competing requirements: sub-megahertz frequencies for optimal detection of microsteatosis and nonlinearity estimation based on waveform distortion over relatively short distances. To meet these challenges, a design is proposed in which ultrasound at 667 kHz is generated by a 50 mm piezoceramic disk and all measurements are made in the plane-wave regime. Given geometrical and physical constraints, all analysis was performed in the time domain. The nonlinearity coefficient ...

Toward treatment of abscesses using non-thermal HIFU

Abscesses are infected walled-off collections of pus and bacteria. They can affect any part of the body. Current treatment is typically limited to antibiotics, catheter drainage and hospitalization, or surgical wash-out when inaccessible, loculated or unresponsive to initial care efforts. Although bacteria can develop drug resistance, they remain susceptible to thermal and mechanical damage. High Intensity Focused Ultrasound (HIFU) generates localized heating and cavitation, and represents a potential new noninvasive treatment modality. This talk describes initial experiments in which non-thermal HIFU treatment was used to inactivate small volumes (100 μL—10 mL) of Escherichia colisuspensions (~1 × 109 cells/mL) with 1 or 2-MHz transducers. Free-field focal acoustic pressures were as high as 16 (9.9) MPa peak positive (negative). Survival was assessed by coliform counting, and by alamarBlue® vital staining. At duty factors of 0.01 or 0.2, and the highest acoustic pressures, there was no biologically signi...