Prasanna Hariharan

HIFU procedures at moderate intensities : effect of large blood vessels

A three-dimensional computational model is presented for studying the efficacy of high-intensity focused ultrasound (HIFU) procedures targeted near large blood vessels. The analysis applies to procedures performed at intensities below the threshold for cavitation, boiling and highly nonlinear propagation, but high enough to increase tissue temperature a few degrees per second. The model is based upon the linearized KZK equation and the bioheat equation in tissue. In the blood vessel the momentum and energy equations are satisfied. The model is first validated in a tissue phantom, to verify the absence of bubble formation and nonlinear effects. Temperature rise and lesion-volume calculations are then shown for different beam locations and orientations relative to a large vessel. Both single and multiple ablations are considered. Results show that when the vessel is located within about a beam width (few mm) of the ultrasound beam, significant reduction in lesion volume is observed due to blood flow. However, for gaps larger than a beam width, blood flow has no major effect on the lesion formation. Under the clinically representative conditions considered, the lesion volume is reduced about 40% (relative to the no-flow case) when the beam is parallel to the blood vessel, compared to about 20% for a perpendicular orientation. Procedures involving multiple ablation sites are affected less by blood flow than single ablations. The model also suggests that optimally focused transducers can generate lesions that are significantly larger (>2 times) than the ones produced by highly focused beams.

Multilaboratory Particle Image Velocimetry Analysis of the FDA Benchmark Nozzle Model to Support Validation of Computational Fluid Dynamics Simulations

This study is part of a FDA-sponsored project to evaluate the use and limitations of computational fluid dynamics (CFD) in assessing blood flow parameters related to medical device safety. In an interlaboratory study, fluid velocities and pressures were measured in a nozzle model to provide experimental validation for a companion round-robin CFD study. The simple benchmark nozzle model, which mimicked the flow fields in several medical devices, consisted of a gradual flow constriction, a narrow throat region, and a sudden expansion region where a fluid jet exited the center of the nozzle with recirculation zones near the model walls. Measurements of mean velocity and turbulent flow quantities were made in the benchmark device at three independent laboratories using particle image velocimetry (PIV). Flow measurements were performed over a range of nozzle throat Reynolds numbers (Re(throat)) from 500 to 6500, covering the laminar, transitional, and turbulent flow regimes. A standard operating procedure was developed for performing experiments under controlled temperature and flow conditions and for minimizing systematic errors during PIV image acquisition and processing. For laminar (Re(throat)=500) and turbulent flow conditions (Re(throat)≥3500), the velocities measured by the three laboratories were similar with an interlaboratory uncertainty of ∼10% at most of the locations. However, for the transitional flow case (Re(throat)=2000), the uncertainty in the size and the velocity of the jet at the nozzle exit increased to ∼60% and was very sensitive to the flow conditions. An error analysis showed that by minimizing the variability in the experimental parameters such as flow rate and fluid viscosity to less than 5% and by matching the inlet turbulence level between the laboratories, the uncertainties in the velocities of the transitional flow case could be reduced to ∼15%. The experimental procedure and flow results from this interlaboratory study (available at http://fdacfd.nci.nih.gov) will be useful in validating CFD simulations of the benchmark nozzle model and in performing PIV studies on other medical device models.

Characterization of high intensity focused ultrasound transducers using acoustic streaming

A new approach for characterizing high intensity focused ultrasound (HIFU) transducers is presented. The technique is based upon the acoustic streaming field generated by absorption of the HIFU beam in a liquid medium. The streaming field is quantified using digital particle image velocimetry, and a numerical algorithm is employed to compute the acoustic intensity field giving rise to the observed streaming field. The method as presented here is applicable to moderate intensity regimes, above the intensities which may be damaging to conventional hydrophones, but below the levels where nonlinear propagation effects are appreciable. Intensity fields and acoustic powers predicted using the streaming method were found to agree within 10% with measurements obtained using hydrophones and radiation force balances. Besides acoustic intensity fields, the streaming technique may be used to determine other important HIFU parameters, such as beam tilt angle or absorption of the propagation medium.

Beam localization in HIFU temperature measurements using thermocouples, with application to cooling by large blood vessels

Experimental studies of thermal effects in high-intensity focused ultrasound (HIFU) procedures are often performed with the aid of fine wire thermocouples positioned within tissue phantoms. Thermocouple measurements are subject to several types of error which must be accounted for before reliable inferences can be made on the basis of the measurements. Thermocouple artifact due to viscous heating is one source of error. A second is the uncertainty regarding the position of the beam relative to the target location or the thermocouple junction, due to the error in positioning the beam at the junction. This paper presents a method for determining the location of the beam relative to a fixed pair of thermocouples. The localization technique reduces the uncertainty introduced by positioning errors associated with very narrow HIFU beams. The technique is presented in the context of an investigation into the effect of blood flow through large vessels on the efficacy of HIFU procedures targeted near the vessel. Application of the beam localization method allowed conclusions regarding the effects of blood flow to be drawn from previously inconclusive (because of localization uncertainties) data. Comparison of the position-adjusted transient temperature profiles for flow rates of 0 and 400ml/min showed that blood flow can reduce temperature elevations by more than 10%, when the HIFU focus is within a 2mm distance from the vessel wall. At acoustic power levels of 17.3 and 24.8W there is a 20- to 70-fold decrease in thermal dose due to the convective cooling effect of blood flow, implying a shrinkage in lesion size. The beam-localization technique also revealed the level of thermocouple artifact as a function of sonication time, providing investigators with an indication of the quality of thermocouple data for a given exposure time. The maximum artifact was found to be double the measured temperature rise, during initial few seconds of sonication.

Radio-Frequency Ablation in a Realistic Reconstructed Hepatic Tissue

This study uses a reconstructed vascular geometry to evaluate the thermal response of tissue during a three-dimensional radiofrequency (rf) tumor ablation. MRI images of a sectioned liver tissue containing arterial vessels are processed and converted into a finite-element mesh. A rf heat source in the form of a spherically symmetric Gaussian distribution, fit from a previously computed profile, is employed. Convective cooling within large blood vessels is treated using direct physical modeling of the heat and momentum transfer within the vessel. Calculations of temperature rise and thermal dose are performed for transient rf procedures in cases where the tumor is located at three different locations near the bifurcation point of a reconstructed artery. Results demonstrate a significant dependence of tissue temperature profile on the reconstructed vasculature and the tumor location. Heat convection through the arteries reduced the steady-state temperature rise, relative to the no-flow case, by up to 70% in the targeted volume. Blood flow also reduced the thermal dose value, which quantifies the extent of cell damage, from approximately 3600 min, for the no-flow condition, to 10 min for basal flow (13.8 cms). Reduction of thermal dose below the threshold value of 240 min indicates ablation procedures that may inadequately elevate the temperature in some regions, thereby permitting possible tumor recursion. These variations are caused by vasculature tortuosity that are patient specific and can be captured only by the reconstruction of the realistic geometry.

Development and characterization of a dynamic lesion phantom for the quantitative evaluation of dynamic contrast-enhanced MRI

PURPOSE To develop a dynamic lesion phantom that is capable of producing physiological kinetic curves representative of those seen in human dynamic contrast-enhanced MRI (DCE-MRI) data. The objective of this phantom is to provide a platform for the quantitative comparison of DCE-MRI protocols to aid in the standardization and optimization of breast DCE-MRI. METHODS The dynamic lesion consists of a hollow, plastic mold with inlet and outlet tubes to allow flow of a contrast agent solution through the lesion over time. Border shape of the lesion can be controlled using the lesion mold production method. The configuration of the inlet and outlet tubes was determined using fluid transfer simulations. The total fluid flow rate was determined using x-ray images of the lesion for four different flow rates (0.25, 0.5, 1.0, and 1.5 ml/s) to evaluate the resultant kinetic curve shape and homogeneity of the contrast agent distribution in the dynamic lesion. High spatial and temporal resolution x-ray measurements were used to estimate the true kinetic curve behavior in the dynamic lesion for benign and malignant example curves. DCE-MRI example data were acquired of the dynamic phantom using a clinical protocol. RESULTS The optimal inlet and outlet tube configuration for the lesion molds was two inlet molds separated by 30° and a single outlet tube directly between the two inlet tubes. X-ray measurements indicated that 1.0 ml/s was an appropriate total fluid flow rate and provided truth for comparison with MRI data of kinetic curves representative of benign and malignant lesions. DCE-MRI data demonstrated the ability of the phantom to produce realistic kinetic curves. CONCLUSIONS The authors have constructed a dynamic lesion phantom, demonstrated its ability to produce physiological kinetic curves, and provided estimations of its true kinetic curve behavior. This lesion phantom provides a tool for the quantitative evaluation of DCE-MRI protocols, which may lead to improved discrimination of breast cancer lesions.

Fda Benchmark Medical Device Flow Models for Cfd Validation.

Computational fluid dynamics (CFD) is increasingly being used to develop blood-contacting medical devices. However, the lack of standardized methods for validating CFD simulations and blood damage predictions limits its use in the safety evaluation of devices. Through a U.S. Food and Drug Administration (FDA) initiative, two benchmark models of typical device flow geometries (nozzle and centrifugal blood pump) were tested in multiple laboratories to provide experimental velocities, pressures, and hemolysis data to support CFD validation. In addition, computational simulations were performed by more than 20 independent groups to assess current CFD techniques. The primary goal of this article is to summarize the FDA initiative and to report recent findings from the benchmark blood pump model study. Discrepancies between CFD predicted velocities and those measured using particle image velocimetry most often occurred in regions of flow separation (e.g., downstream of the nozzle throat, and in the pump exit diffuser). For the six pump test conditions, 57% of the CFD predictions of pressure head were within one standard deviation of the mean measured values. Notably, only 37% of all CFD submissions contained hemolysis predictions. This project aided in the development of an FDA Guidance Document on factors to consider when reporting computational studies in medical device regulatory submissions. There is an accompanying podcast available for this article. Please visit the journal’s Web site (www.asaiojournal.com) to listen.

HIFU lesion volume as a function of sonication time, as determined by MRI, histology, and computations.

Characterization of high-intensity focused ultrasound (HIFU) systems using ex vivo tissues is an important part of the preclinical testing for new HIFU devices. In ex vivo characterization, the lesion volume produced by the absorption of HIFU energy is quantified as operational parameters are varied. This paper examines the three methods used for lesion-volume quantification: histology, magnetic resonance (MR) imaging, and numerical calculations. The methods were studied in the context of a clinically relevant problem for HIFU procedures--that of quantifying the change in the lesion volume with changing sonication time. The lesion volumes of sonicated samples of porcine liver were determined using the three methods, at focal intensities ranging from 800 W/cm(2) to 1700 W/cm(2) and sonication times between 20 s and 40 s. It was found that histology consistently yielded lower lesion volumes than the other two methods, and the calculated values were below magnetic resonance imaging (MRI) at high applied energies. Still, the three methods agreed with each other to within a +/-10% difference for all of the experiments. Increasing the sonication time produced much larger changes in the lesion volume than increasing the acoustic intensity, for the same total energy expenditure, at lower energy (less than 1000 J) levels. At higher energy levels, (around 1500 J), increasing the sonication time and increasing the intensity produced roughly the same change in the lesion volume for the same total energy expenditure.

Localization of focused-ultrasound beams in a tissue phantom, using remote thermocouple arrays

In focused-ultrasound procedures such as vessel cauterization or clot lysis, targeting accuracy is critical. To investigate the targeting accuracy of the focused-ultrasound systems, tissue phantoms embedded with thermocouples can be employed. This paper describes a method that utilizes an array of thermocouples to localize the focused ultrasound beam. All of the thermocouples are located away from the beam, so that thermocouple artifacts and sensor interference are minimized. Beam propagation and temperature rise in the phantom are simulated numerically, and an optimization routine calculates the beam location that produces the best agreement between the numerical temperature values and those measured with thermocouples. The accuracy of the method was examined as a function of the array characteristics, including the number of thermocouples in the array and their orientation. For exposures with a 3.3-MHz source, the remote-thermocouple technique was able to predict the focal position to within 0.06 mm. Once the focal location is determined using the localization method, temperatures at desired locations (including the focus) can be estimated from remote thermocouple measurements by curve fitting an analytical solution to the heat equation. Temperature increases in the focal plane were predicted to within 5% agreement with measured values using this method.

Enhancement of ICRP's Lung Deposition Model for Pathogenic Bioaerosols

Terrorist attacks using pathogenic bioaerosols pose a significant public-health threat. Modeling the risk associated with such attacks is valuable from the standpoint of disaster preparedness. To attain greater flexibility in bioterrorism risk modeling, we have developed an open-source lung deposition code based on the International Committee for Radiological Protection (ICRP) Publication 66 (ICRP 1994). This article describes modifications to ICRPs lung deposition model to fit the bioaerosol context and discusses the impact of exposure from a few monodisperse pathogenic toxins such as botulinum toxin, influenza virus, and Bacillus anthracis to infants and adults. As most existing commercial lung deposition codes are not open-source, this code provides users a platform template that can be modified to meet their needs.