Integration of a 2D ultrasound transducer array with front-end signal conditioning electronics po... more Integration of a 2D ultrasound transducer array with front-end signal conditioning electronics poses significant fabrication and packaging challenges due to the required number of elements and small element pitch. In this paper, we demonstrate a CMUT-in-CMOS approach that produces ultrasonic transducers and circuits on a single chip using a standard foundry CMOS process, augmented only with two blanket post-process steps
Journal of Ultrasound in Medicine Official Journal of the American Institute of Ultrasound in Medicine, Dec 1, 2012
ObjectivesThree-dimensional (3D) umbilical cord blood volume flow measurement with the intention ... more ObjectivesThree-dimensional (3D) umbilical cord blood volume flow measurement with the intention of providing a straightforward, consistent, and accurate method that overcomes the limitations associated with traditional pulsed-wave Doppler flow measurement and provides a means by which to recognize and manage at-risk pregnancies.MethodsThe first study involved 3D ultrasound volume flow measurements in seven healthy ewes whose pregnancies ranged from 18 to 19 weeks’ gestation (7 singletons). Sonographic umbilical arterial and venous flow measurements from each fetus were compared to the corresponding average measured arterial/venous flow to assess feasibility of measurement in a static vessel. A second complementary study involved 3D ultrasound volume flow measurements in seven healthy women whose pregnancies ranged from 17.9 to 36.3 weeks’ gestation (6 singletons, 1 twin). Umbilical venous flow measurements were compared to similar flow measurements reported in the literature. Pregnancy outcomes were abstracted from the medical records of the recruited patients.ResultsIn the fetal sheep model, arterial/venous flow comparisons yielded errors of 10% or less for eight out of the nine measurements. In the clinical study, venous flow measurements showed agreement with the literature over a range of gestational ages. Two of the seven patients in the clinical study demonstrated lower flow than anticipated for gestational age; one was subsequently diagnosed with intrauterine growth restriction and the other with preeclampsia.ConclusionsAccurate measurements of umbilical blood volume flow can be performed with relative ease in both the sheep model and in humans using the proposed 3D ultrasound flow measurement technique. Results encourage further development of the method as a means for diagnosis and identification of at-risk pregnancies.
Nanodroplet-mediated histotripsy (NMH) is a targeted ablation technique combining histotripsy wit... more Nanodroplet-mediated histotripsy (NMH) is a targeted ablation technique combining histotripsy with nanodroplets that can be selectively delivered to tumor cells. In two previous studies, polymer-encapsulated perfluoropentane nanodroplets were used to generate well-defined ablation similar to that obtained with histotripsy, but at significantly lower pressure, when NMH therapy was applied at a pulse repetition frequency (PRF) of 10 Hz. However, cavitation was not maintained over multiple pulses when ultrasound was applied at a lower PRF (i.e., 1-5 Hz). We hypothesized that nanodroplets with a higher-boiling-point perfluorocarbon core would provide sustainable cavitation nuclei, allowing cavitation to be maintained over multiple pulses, even at low PRF, which is needed for efficient and complete tissue fractionation via histotripsy. To test this hypothesis, we investigated the effects of droplet composition on NMH therapy by applying histotripsy at various frequencies (345 kHz, 500 kH...
2010 IEEE International Ultrasonics Symposium, 2010
ABSTRACT As ultrasound imagers become increasingly portable and lower cost, breakthroughs in tran... more ABSTRACT As ultrasound imagers become increasingly portable and lower cost, breakthroughs in transducer technology will be needed in order to provide excellent imaging (ideally 3D/4D) while maintaining the affordability needed for portable systems. This paper presents a 32x32 ultrasound array prototype, manu- factured using a CMUT-in-CMOS approach whereby transducer elements and circuit components are integrated on a single chip using a straightforward and cost-effective manufacturing ap- proach. The array contains 1,024 elements arranged on a hex- agonal grid with half-wavelength pitch (target of 2-4 MHz). On- chip CMOS buffers and multiplexers are used to maintain signal integrity and to reduce the number of output leads. For testing and imaging studies, the array has been interfaced to a commer- cial imager as well as a set of custom transmit and receive elec- tronics. This work sets the stage for full-scale 2D arrays that will provide unprecedented image quality at a very low cost.
Nanodroplet-mediated histotripsy (NMH) is a targeted ultrasound ablation technique combining hist... more Nanodroplet-mediated histotripsy (NMH) is a targeted ultrasound ablation technique combining histotripsy with nanodroplets that can be selectively delivered to tumor cells for targeted tumor ablation. In a previous study, it was reported that by use of extremely short, high-pressure pulses, histotripsy cavitation bubbles were generated in regions containing nanodroplets at significantly lower pressure (∼10.8 MPa) than without nanodroplets (∼28 MPa) at 500 kHz. Furthermore, it was hypothesized that lower frequency would improve the effectiveness of NMH by increasing the size of the focal region, increasing bubble expansion, and decreasing the cavitation threshold. In this study, we investigated the effects of ultrasound frequency (345 kHz, 500 kHz, 1.5 MHz, and 3 MHz) on NMH. First, the NMH cavitation threshold was measured in tissue phantoms with and without nanodroplets, with results indicating that the NMH threshold was significantly below the histotripsy intrinsic threshold at al...
International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group, Jan 24, 2015
In high intensity focused ultrasound (HIFU) therapy, an ultrasound beam is focused within the bod... more In high intensity focused ultrasound (HIFU) therapy, an ultrasound beam is focused within the body to locally affect the targeted site without damaging intervening tissues. The most common HIFU regime is thermal ablation. Recently there has been increasing interest in generating purely mechanical lesions in tissue (histotripsy). This paper provides an overview of several studies on the development of histotripsy methods toward clinical applications. Two histotripsy approaches and examples of their applications are presented. In one approach, sequences of high-amplitude, short (microsecond-long), focused ultrasound pulses periodically produce dense, energetic bubble clouds that mechanically disintegrate tissue. In an alternative approach, longer (millisecond-long) pulses with shock fronts generate boiling bubbles and the interaction of shock fronts with the resulting vapour cavity causes tissue disintegration. Recent preclinical studies on histotripsy are reviewed for treating benign...
Abstract Ultrasound can be used to phase transition perfluorocarbon (PFC) droplets into gas bubbl... more Abstract Ultrasound can be used to phase transition perfluorocarbon (PFC) droplets into gas bubbles, a process known as acoustic droplet vaporization (ADV). In vivo blood flow reductions can then be achieved using the ADV bubbles. An in situ ultrasonic measurement of this blood flow reduction is desirable. Since, in a simple model, initial flow reduction is proportional to the number of bubbles, and the mean echo power (MEP) in a B-mode image is related to the number of bubbles (off resonant scattering), it is hypothesized that the ...
ABSTRACT Spatial and temporal control over the expression of growth/differentiation factors is of... more ABSTRACT Spatial and temporal control over the expression of growth/differentiation factors is of great interest for regeneration of bone, but technologies capable of providing tight and active control over gene expression remain elusive. We propose the use of focused ultrasound for the targeted activation of heat shock-sensitive expression systems in engineered bone. We report in vitro results with cells that express firefly luciferase (fLuc) under the control of a heat shock protein promoter. Cells were embedded in fibrin scaffolds and exposed to focused ultrasound, using a custom 3.3MHz transducer (focal length 4", f-number 1.33", focal dimension 1.2mm lateral FWHM) in CW mode for 2-20 minutes at intensities ISPTA=120-440 W/cm2. The kinetics of ultrasound-mediated activation of the cells was compared with that of strictly thermal activation. Bioluminescence imaging revealed fLuc expression in an area >=2.5mm in diameter at the position of the ultrasound focus, and the diameter and intensity of the signal increased with the amplitude of the acoustic energy. We also found that ultrasound activated fLuc expression with substantially shorter exposures than thermal activation. Our results demonstrate the potential for focused ultrasound to selectively activate the expression of a gene of interest in an engineered tissue and suggest that focused ultrasound activates the heat shock pathway by a combination of thermal and non-thermal mechanisms.
[underline Purpose:] Acoustic droplet vaporization (ADV) shows promise for the spatial control an... more [underline Purpose:] Acoustic droplet vaporization (ADV) shows promise for the spatial control and acceleration of thermal lesion production. In this study, we investigated the hypothesis that ADV bubbles can substantially enhance HIFU ablation by increasing and ...
The Journal of the Acoustical Society of America, 2010
Clinical volumetric blood flow estimation relies on several assumptions. Among them are cylindric... more Clinical volumetric blood flow estimation relies on several assumptions. Among them are cylindrical vessel geometry, symmetric flow profile, and Doppler angle. None of them are known well enough to obtain clinically relevant estimates. 3-D color flow acquisition circumvents these assumptions, posing a viable tool for in vivo blood volume flow analysis. A 4-D cardiac scanner operating a 2-D array for real-time 3-D color flow imaging [GE Healthcare, Milwaukee, WI] was used. The array was positioned to fully intersect a 2-cm-diameter flow tube with the constant-depth plane (CPlane). Blood mimicking fluid was circulated at up to 6 l/min using a cardiac bypass pump (60 and 80 beats/min). A trigger source synchronized the pump and scanner. Data volumes were acquired equally spaced throughout the cardiac cycle. Temporally resolved volume flow was derived from CPlane data integration using Doppler power partial volume correction. Results show less than 7% mean flow error for temporally reso...
The Journal of the Acoustical Society of America, 2010
Micron- and nano-sized colloids are being studied in diagnostic and therapeutic applications of u... more Micron- and nano-sized colloids are being studied in diagnostic and therapeutic applications of ultrasound (US). Unlike clinically utilized microbubbles, emulsions possess unique physiochemical properties that could translate into distinct, clinical benefits beyond conventional contrast agents. Droplets, composed of a superheated liquid, can be phase transitioned into bubbles using US, a process known as acoustic droplet vaporization (ADV). Droplets, transpulmonary in size, transition into bubbles upon ADV and can reach diameters that occlude capillaries and arrest blood flow in the vascular bed. Examples of ADV in diagnostic and therapeutic applications will be presented. First, ADV has been used in phase aberration correction in transcranial US imaging. Second, ADV-generated microbubbles can reduce and occlude renal perfusion in vivo. Third, the effects of thermal therapy using high-intensity focused ultrasound (HIFU) has been enhanced and controlled more effectively using ADV. Fo...
Acoustic vaporization dynamics of a superheated dodecafluoropentane (DDFP) microdroplet inside a ... more Acoustic vaporization dynamics of a superheated dodecafluoropentane (DDFP) microdroplet inside a microtube and the resulting bubble evolution is investigated in the present work. This work is motivated by a developmental gas embolotherapy technique that is intended to treat cancers by infarcting tumors using gas bubbles. A combined theoretical and computational approach is utilized and compared with the experiments to understand the evolution process and to estimate the resulting stress distribution associated with vaporization event. The transient bubble growth is first studied by ultra-high speed imaging and then theoretical and computational modeling is used to predict the entire bubble evolution process. The evolution process consists of three regimes: an initial linear rapid spherical growth followed by a linear compressed oval shaped growth and finally a slow asymptotic nonlinear spherical bubble growth. Although the droplets are small compared to the tube diameter, the bubble...
Integration of a 2D ultrasound transducer array with front-end signal conditioning electronics po... more Integration of a 2D ultrasound transducer array with front-end signal conditioning electronics poses significant fabrication and packaging challenges due to the required number of elements and small element pitch. In this paper, we demonstrate a CMUT-in-CMOS approach that produces ultrasonic transducers and circuits on a single chip using a standard foundry CMOS process, augmented only with two blanket post-process steps
Journal of Ultrasound in Medicine Official Journal of the American Institute of Ultrasound in Medicine, Dec 1, 2012
ObjectivesThree-dimensional (3D) umbilical cord blood volume flow measurement with the intention ... more ObjectivesThree-dimensional (3D) umbilical cord blood volume flow measurement with the intention of providing a straightforward, consistent, and accurate method that overcomes the limitations associated with traditional pulsed-wave Doppler flow measurement and provides a means by which to recognize and manage at-risk pregnancies.MethodsThe first study involved 3D ultrasound volume flow measurements in seven healthy ewes whose pregnancies ranged from 18 to 19 weeks’ gestation (7 singletons). Sonographic umbilical arterial and venous flow measurements from each fetus were compared to the corresponding average measured arterial/venous flow to assess feasibility of measurement in a static vessel. A second complementary study involved 3D ultrasound volume flow measurements in seven healthy women whose pregnancies ranged from 17.9 to 36.3 weeks’ gestation (6 singletons, 1 twin). Umbilical venous flow measurements were compared to similar flow measurements reported in the literature. Pregnancy outcomes were abstracted from the medical records of the recruited patients.ResultsIn the fetal sheep model, arterial/venous flow comparisons yielded errors of 10% or less for eight out of the nine measurements. In the clinical study, venous flow measurements showed agreement with the literature over a range of gestational ages. Two of the seven patients in the clinical study demonstrated lower flow than anticipated for gestational age; one was subsequently diagnosed with intrauterine growth restriction and the other with preeclampsia.ConclusionsAccurate measurements of umbilical blood volume flow can be performed with relative ease in both the sheep model and in humans using the proposed 3D ultrasound flow measurement technique. Results encourage further development of the method as a means for diagnosis and identification of at-risk pregnancies.
Nanodroplet-mediated histotripsy (NMH) is a targeted ablation technique combining histotripsy wit... more Nanodroplet-mediated histotripsy (NMH) is a targeted ablation technique combining histotripsy with nanodroplets that can be selectively delivered to tumor cells. In two previous studies, polymer-encapsulated perfluoropentane nanodroplets were used to generate well-defined ablation similar to that obtained with histotripsy, but at significantly lower pressure, when NMH therapy was applied at a pulse repetition frequency (PRF) of 10 Hz. However, cavitation was not maintained over multiple pulses when ultrasound was applied at a lower PRF (i.e., 1-5 Hz). We hypothesized that nanodroplets with a higher-boiling-point perfluorocarbon core would provide sustainable cavitation nuclei, allowing cavitation to be maintained over multiple pulses, even at low PRF, which is needed for efficient and complete tissue fractionation via histotripsy. To test this hypothesis, we investigated the effects of droplet composition on NMH therapy by applying histotripsy at various frequencies (345 kHz, 500 kH...
2010 IEEE International Ultrasonics Symposium, 2010
ABSTRACT As ultrasound imagers become increasingly portable and lower cost, breakthroughs in tran... more ABSTRACT As ultrasound imagers become increasingly portable and lower cost, breakthroughs in transducer technology will be needed in order to provide excellent imaging (ideally 3D/4D) while maintaining the affordability needed for portable systems. This paper presents a 32x32 ultrasound array prototype, manu- factured using a CMUT-in-CMOS approach whereby transducer elements and circuit components are integrated on a single chip using a straightforward and cost-effective manufacturing ap- proach. The array contains 1,024 elements arranged on a hex- agonal grid with half-wavelength pitch (target of 2-4 MHz). On- chip CMOS buffers and multiplexers are used to maintain signal integrity and to reduce the number of output leads. For testing and imaging studies, the array has been interfaced to a commer- cial imager as well as a set of custom transmit and receive elec- tronics. This work sets the stage for full-scale 2D arrays that will provide unprecedented image quality at a very low cost.
Nanodroplet-mediated histotripsy (NMH) is a targeted ultrasound ablation technique combining hist... more Nanodroplet-mediated histotripsy (NMH) is a targeted ultrasound ablation technique combining histotripsy with nanodroplets that can be selectively delivered to tumor cells for targeted tumor ablation. In a previous study, it was reported that by use of extremely short, high-pressure pulses, histotripsy cavitation bubbles were generated in regions containing nanodroplets at significantly lower pressure (∼10.8 MPa) than without nanodroplets (∼28 MPa) at 500 kHz. Furthermore, it was hypothesized that lower frequency would improve the effectiveness of NMH by increasing the size of the focal region, increasing bubble expansion, and decreasing the cavitation threshold. In this study, we investigated the effects of ultrasound frequency (345 kHz, 500 kHz, 1.5 MHz, and 3 MHz) on NMH. First, the NMH cavitation threshold was measured in tissue phantoms with and without nanodroplets, with results indicating that the NMH threshold was significantly below the histotripsy intrinsic threshold at al...
International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group, Jan 24, 2015
In high intensity focused ultrasound (HIFU) therapy, an ultrasound beam is focused within the bod... more In high intensity focused ultrasound (HIFU) therapy, an ultrasound beam is focused within the body to locally affect the targeted site without damaging intervening tissues. The most common HIFU regime is thermal ablation. Recently there has been increasing interest in generating purely mechanical lesions in tissue (histotripsy). This paper provides an overview of several studies on the development of histotripsy methods toward clinical applications. Two histotripsy approaches and examples of their applications are presented. In one approach, sequences of high-amplitude, short (microsecond-long), focused ultrasound pulses periodically produce dense, energetic bubble clouds that mechanically disintegrate tissue. In an alternative approach, longer (millisecond-long) pulses with shock fronts generate boiling bubbles and the interaction of shock fronts with the resulting vapour cavity causes tissue disintegration. Recent preclinical studies on histotripsy are reviewed for treating benign...
Abstract Ultrasound can be used to phase transition perfluorocarbon (PFC) droplets into gas bubbl... more Abstract Ultrasound can be used to phase transition perfluorocarbon (PFC) droplets into gas bubbles, a process known as acoustic droplet vaporization (ADV). In vivo blood flow reductions can then be achieved using the ADV bubbles. An in situ ultrasonic measurement of this blood flow reduction is desirable. Since, in a simple model, initial flow reduction is proportional to the number of bubbles, and the mean echo power (MEP) in a B-mode image is related to the number of bubbles (off resonant scattering), it is hypothesized that the ...
ABSTRACT Spatial and temporal control over the expression of growth/differentiation factors is of... more ABSTRACT Spatial and temporal control over the expression of growth/differentiation factors is of great interest for regeneration of bone, but technologies capable of providing tight and active control over gene expression remain elusive. We propose the use of focused ultrasound for the targeted activation of heat shock-sensitive expression systems in engineered bone. We report in vitro results with cells that express firefly luciferase (fLuc) under the control of a heat shock protein promoter. Cells were embedded in fibrin scaffolds and exposed to focused ultrasound, using a custom 3.3MHz transducer (focal length 4", f-number 1.33", focal dimension 1.2mm lateral FWHM) in CW mode for 2-20 minutes at intensities ISPTA=120-440 W/cm2. The kinetics of ultrasound-mediated activation of the cells was compared with that of strictly thermal activation. Bioluminescence imaging revealed fLuc expression in an area >=2.5mm in diameter at the position of the ultrasound focus, and the diameter and intensity of the signal increased with the amplitude of the acoustic energy. We also found that ultrasound activated fLuc expression with substantially shorter exposures than thermal activation. Our results demonstrate the potential for focused ultrasound to selectively activate the expression of a gene of interest in an engineered tissue and suggest that focused ultrasound activates the heat shock pathway by a combination of thermal and non-thermal mechanisms.
[underline Purpose:] Acoustic droplet vaporization (ADV) shows promise for the spatial control an... more [underline Purpose:] Acoustic droplet vaporization (ADV) shows promise for the spatial control and acceleration of thermal lesion production. In this study, we investigated the hypothesis that ADV bubbles can substantially enhance HIFU ablation by increasing and ...
The Journal of the Acoustical Society of America, 2010
Clinical volumetric blood flow estimation relies on several assumptions. Among them are cylindric... more Clinical volumetric blood flow estimation relies on several assumptions. Among them are cylindrical vessel geometry, symmetric flow profile, and Doppler angle. None of them are known well enough to obtain clinically relevant estimates. 3-D color flow acquisition circumvents these assumptions, posing a viable tool for in vivo blood volume flow analysis. A 4-D cardiac scanner operating a 2-D array for real-time 3-D color flow imaging [GE Healthcare, Milwaukee, WI] was used. The array was positioned to fully intersect a 2-cm-diameter flow tube with the constant-depth plane (CPlane). Blood mimicking fluid was circulated at up to 6 l/min using a cardiac bypass pump (60 and 80 beats/min). A trigger source synchronized the pump and scanner. Data volumes were acquired equally spaced throughout the cardiac cycle. Temporally resolved volume flow was derived from CPlane data integration using Doppler power partial volume correction. Results show less than 7% mean flow error for temporally reso...
The Journal of the Acoustical Society of America, 2010
Micron- and nano-sized colloids are being studied in diagnostic and therapeutic applications of u... more Micron- and nano-sized colloids are being studied in diagnostic and therapeutic applications of ultrasound (US). Unlike clinically utilized microbubbles, emulsions possess unique physiochemical properties that could translate into distinct, clinical benefits beyond conventional contrast agents. Droplets, composed of a superheated liquid, can be phase transitioned into bubbles using US, a process known as acoustic droplet vaporization (ADV). Droplets, transpulmonary in size, transition into bubbles upon ADV and can reach diameters that occlude capillaries and arrest blood flow in the vascular bed. Examples of ADV in diagnostic and therapeutic applications will be presented. First, ADV has been used in phase aberration correction in transcranial US imaging. Second, ADV-generated microbubbles can reduce and occlude renal perfusion in vivo. Third, the effects of thermal therapy using high-intensity focused ultrasound (HIFU) has been enhanced and controlled more effectively using ADV. Fo...
Acoustic vaporization dynamics of a superheated dodecafluoropentane (DDFP) microdroplet inside a ... more Acoustic vaporization dynamics of a superheated dodecafluoropentane (DDFP) microdroplet inside a microtube and the resulting bubble evolution is investigated in the present work. This work is motivated by a developmental gas embolotherapy technique that is intended to treat cancers by infarcting tumors using gas bubbles. A combined theoretical and computational approach is utilized and compared with the experiments to understand the evolution process and to estimate the resulting stress distribution associated with vaporization event. The transient bubble growth is first studied by ultra-high speed imaging and then theoretical and computational modeling is used to predict the entire bubble evolution process. The evolution process consists of three regimes: an initial linear rapid spherical growth followed by a linear compressed oval shaped growth and finally a slow asymptotic nonlinear spherical bubble growth. Although the droplets are small compared to the tube diameter, the bubble...
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Papers by Jeffrey Fowlkes