Subhashish Dasgupta

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.

Transport and reaction of nanoliter samples in a microfluidic reactor using electro-osmotic flow

The primary focus of the paper is to establish both numerical and experimental methods to control the concentration of samples in a microreactor well. The concentration of the reacting samples is controlled by varying the initial sample size and electric field. Further, the paper numerically investigates the feasibility of mixing and reacting nanoliter samples with a wide variation in reaction rates in the microreactor driven by electro-osmotic pumping. Two discrete samples are measured and transported to the microreactor simultaneously by electro-osmotic pinching and switching. The transported samples are mixed in the microreactor and floated for 4.5 s for reaction to occur. It is seen that the normalized concentration of the product increases from 0.25 to 0.45 during that period. Also the effects of sample size and applied electric field on sample concentration during the switching process are studied. It is found that the normalized final sample concentration increases from 0.03 to 0.11 with an increase in sample size from 60 to 150 μm, at a constant electric field. Further, by increasing the electric field from 100 to 1000 V cm −1 , at a constant sample size, there is a significant decrease in the final concentration of the sample from 0.14 to 0.04. Our studies also show that the normalized product concentration depends on the reaction rate and increases from 0.28 to 0.48 as the reaction rate increases from 10 L mol −1 s −1 to 10 5 Lm ol −1 s −1 . However, the increase in the reaction rate beyond 10 5 Lm ol −1 s −1 does not influence the product concentration for the present design of the microreactor. Our microreactor with improved mixing can be used for assessing reactions of biological samples. The optimized sample size along with a controlled electric field for sample injection forms the basis for developing a prototype of a microreactor device for high throughput drug screening.

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.

Reduction of Noise From MR Thermometry Measurements During HIFU Characterization Procedures

Magnetic resonance (MR) thermometry is a valuable method for characterizing thermal fields generated by high intensity focused ultrasound (HIFU) transducers in tissue phantoms and excised tissues. However, infiltration of noise signals generated by external rf sources into the scanner orifice limits the ability of the scanner to measure temperature rise during the heating or ablation phase. In this study, magnetic resonance interferometry (MRI) monitored HIFU ablations are performed on freshly excised porcine liver samples, at varying sonication times, 20 s, 30 s, and 40 s at a constant acoustic intensity level of 1244 W/cm 2 . Temperature throughout the procedure was measured using proton resonant frequency MR thermometry. Without filtering, reliable temperature measurements during the heating phase could not be obtained since temperature maps appeared blurred and analysis was impossible. Also, measurements acquired during the cooling phase decayed manifested an unrealistically slow rate of temperature decay. This abnormally slow rate was confirmed with computational results. A low-pass RC filter circuit was subsequently incorporated into the experimental setup to prevent infiltration of noise signals in the MRI orifice. This modified RC filter circuit allowed noninvasive measurement of the HIFU induced temperature rise during the heating phase followed by temperature decay during cooling. The measured data were within 13% agreement with the temperature rise computed by solving the acoustic and heat equations.

Characterization Methods of High-Intensity Focused Ultrasound-Induced Thermal Field

Publisher Summary High-intensity focused ultrasound (HIFU) is a minimally invasive medical procedure used for thermal ablation of tumors and uterine fibroids, vessel cauterization, thrombolysis, drug delivery, and gene activation. Tissue damage via ultrasound is achieved by the conversion of the mechanical energy of acoustic waves to thermal energy as the ultrasound propagates through the tissue. Unlike other hyperthermia techniques such as radio frequency (RF) and laser ablation procedures, during a typical HIFU procedure, a large amount of energy is deposited in a short duration causing sudden, drastic, and localized rise in tissue temperature. This chapter focuses on the new preclinical testing methods developed for acoustic intensity and temperature measurements at HIFU energy levels. A preliminary step in the analysis of new medical devices involving high-intensity ultrasound is the determination of the acoustic intensity field in a liquid medium. Medical ultrasound fields generated by focused transducers are usually characterized in water using calorimetry methods, hydrophones, and radiation force balance techniques. The chapter also describes alternate characterization methods and acoustic streaming-based method. Thin wire thermocouples embedded in tissue-mimicking materials or excised tissues have been popularly used as a cost-effective method for measuring the HIFU-induced transient temperature rise. An improvement in HIFU characterization studies is the development of nonperturbing methods, to assess the thermal field in a tissue medium. In this method direct sonication of thermocouple junctions is avoided to prevent artifacts in the temperature data. The beam is focused at locations off the thermocouple junctions and the temperature rise at the remote junctions is measured.

Effects of Microchannel Cross-Section and Applied Electric Field on Electroosmotic Mobility

In this work we report on the numerical and experimental investigation of the effects of channel cross-section and applied electric field on electroosmotic flow (EOF) mobility in polydimethylsiloxane (PDMS)/glass hybrid microchannels. The experimental results are used to calibrate and validate the simulation model to solve the Navier-Stokes equation for fluid flow and Poisson equation to resolve the external electric field. According to the Helmholtz Smoluchowski equation the electroosmotic mobility (muEO) is independent of channel cross-section and applied electric field. Contrary to the above relationship, the results presented in this work indicate that muEO is not constant but changes with channel cross-section as well as the applied electric field. The results of this work will be useful in determining the optimum channel dimensions for a desired electroosmotic velocity at a given applied electric field.

Electroosmotic Injection and Chemical Kinetics in Micro Reactors

The study of fluid flow in microchannels is of significant interest due to its application in a wide area of fields ranging from microscale flow injection, cooling of microchips, fuel vaporizer and micro reactors for chemical and biological systems. Design of effective electrokinetic micro reactors requires in-depth understanding of the electrokinetic phenomena and bulk reactions of species in the micro reactor. Although electrokinetic flows are popularly used for applications in the field of capillary electrophoresis (CE) [1], the phenomena of electroosmosis can be conveniently used for bulk transport and mixing of reagents. Electroosmosis occurs when the electrical double layer (EDL) near a solid-liquid interface is created by an external electric field. The uniqueness of electroosmotic flow (EOF) is characterized by plug velocity profile having uniform flow. Devasenathipathy et al. [2] showed that EOF offers a number of significant advantages over conventional pressure driven flow like reduced sample diffusion and controlled sample movement.Copyright

Temperature Rise in Tissue Mimicking Material During HIFU Procedures

High Intensity Focused Ultrasound (HIFU) has shown considerable promise as a minimally-invasive technique for various therapeutic applications such as tumor ablation and vessel cauterization. The efficacies of these HIFU procedures depend on various operational parameters such as total acoustic power, pulse duration and transducer dimensions. In this study, the effect of total acoustic power on the tissue temperature rise is studied both experimentally and numerically. Experimentally, HIFU ablations, at different acoustic powers, were carried out in a tissue mimicking material embedded with thermocouples. Temperature rise measured from the in-vitro experiments were then validated with the numerical computations. Results show that experimental and numerical temperature rise match accurately. Our numerical model was able to predict the peak temperature rise within ∼12% of the experimental results. Results also show that the tissue temperature rise is linearly proportional to the input acoustic power. For the acoustic power levels considered in this study, the results suggest that acoustic non-linearity does not play a major role on the tumor ablation procedure.© 2007 ASME

Delineation of Noise Signals From MRI Measured Temperature Rise During HIFU Ablation Procedure

A relatively recent and non invasive method for characterizing thermal fields generated by high intensity focused ultrasound (HIFU) transducers is Magnetic Resonance (MR) Thermometry method. However, noise signals generated by external RF sources infiltrate the scanner orifice and limit its ability to measure temperature rise during the heating or ablation phase. In this study, MRI monitored HIFU ablations are performed on freshly excised porcine liver samples, at varying sonication times, 20, 30 and 40 s at a constant acoustic intensity level of 1244 W/cm2. Temperature rise during the procedure is measured using Proton Resonant Frequency MR thermometry. Preliminary experiments without an adequate noise filter, failed to record temperature rise during the heating phase. A low pass R-C filter circuit is subsequently incorporated into the experimental set up to prevent infiltration of noise signals in the MRI orifice. This modified RC filter enables measurement of temperature rise during the heating phase followed by temperature decay during cooling. The measured data is within 12% agreement with the temperature rise computed by solving the acoustic and heat equations.© 2011 ASME

Reduction in Beam Positioning Error During HIFU Ablation Studies in Tissue Phantoms

Measurements of high intensity focused ultrasound (HIFU) induced temperature rise using thermocouples in tissue phantoms are subject to several types of error which must be accounted for in order to accurately assess the thermal field and predict the outcome of clinical procedures. Thermocouple artifacts due to viscous heating is one source of error. A second source of error involves displacement of the beam relative to the targeted thermocouple junction, due to the difficulty in precisely positioning the very narrow beam. This paper presents an iterative method for removing inaccuracies due to positioning error from the measured temperature data. The refined data is used to quantify the effect of blood flow through large vessels on the efficacy of HIFU procedures. It was determined that blood flow cooling effect causes an order of magnitude decrease in thermal dose at the target within 2 mm of the blood vessel, potentially resulting in incomplete ablation of the tumor. The technique also reveals that thermocouple artifacts exist in significant proportions from about 0.5 to 2.2 times the computed temperature rise in the initial few seconds. The iterative method can aid in clinical procedure planning, especially in predicting the proper HIFU intensity and duration for complete destruction of tumors.Copyright