Stephen Barnes

Spatial and Temporal-Controlled Tissue Heating on a Modified Clinical Ultrasound Scanner for Generating Mild Hyperthermia in Tumors

A new system is presented for generating controlled tissue heating with a clinical ultrasound scanner, and initial in vitro and in vivo results are presented that demonstrate both transient and sustained heating in the mild-hyperthermia range of 37°C-42°C. The system consists of a Siemens Antares ultrasound scanner, a custom dual-frequency three-row transducer array and an external temperature feedback control system. The transducer has two outer rows that operate at 1.5 MHz for tissue heating and a center row that operates at 5 MHz for B-mode imaging to guide the therapy. We compare the field maps obtained using a hydrophone against calculations of the ultrasound beam based on monochromatic and linear assumptions. Using the finite-difference time-domain (FDTD) method, we compare predicted time-dependent thermal profiles to measured profiles for soy tofu as a tissue-mimicking phantom. In vitro results show differential heating of 6°C for chicken breast and tofu. In vivo tests of the system were performed on three mice bearing Met-1 tumors, which is a model of aggressive, metastatic, and highly vascular breast cancer. In superficially implanted tumors, we demonstrate controlled heating to 42°C. We show that the system is able to maintain the temperature to within 0.1°C of the desired temperature both in vitro and in vivo.

5A-3 Spatial and Temporal Controlled Tissue Heating on a Modified Clinical Ultrasound Scanner for Generating Mild Hyperthermia in Tumors

We present a new system for generating controlled tissue heating with a clinical ultrasound scanner and initial in vitro and in vivo results that demonstrate both transient and sustained heating in the mild- hyperthermia range of 37-42degC. The system consists of a Siemens Antarestrade ultrasound scanner, a custom dual-frequency 3-row transducer array, and an external temperature feedback control system. The transducer has 2 outer rows that operate at 1.5 MHz for tissue heating and a center row that operates at 5 MHz for B-mode imaging. Temperature measurement is accomplished using a thermocouple encased within a 29 gauge stainless steel needle. The temperature measurements are fed into a modified proportional-differential-integral (PID) control loop programmed in LabVIEWtrade running on an external PC. Modifications to the PID loop include a limited bandwidth differential section and integrator anti-windup. The PID loop controls duty cycle by varying the PRF on a SIEMENS Antares ultrasound scanner, and the resulting PRF update rate is approximately 3 Hz. The heating beam is directed using the pulsed-Doppler cursor with reference to a 5 MHz B-mode image. B-mode updates also occur at approximately 3 Hz. In vitro results show differential heating of chicken breast of 8degC at the beam focus. We show that the system is able to maintain the temperature to within 0.1degC of the desired temperature both in vitro and in vivo. In vivo tests of the system were performed on a mouse bearing Met-1 tumors, which is a model of aggressive, metastatic and highly vascular breast cancer. In superficially implanted tumors, we demonstrate controlled heating to temperatures in the 39-42degC range, which is ideal for releasing drugs from thermally-sensitive liposomes.

Acoustic backscatter and effective scatterer size estimates using a 2D CMUT transducer

Compared to conventional piezoelectric transducers, new capacitive microfabricated ultrasonic transducer (CMUT) technology is expected to offer a broader bandwidth, higher resolution and advanced 3D/4D imaging inherent in a 2D array. For ultrasound scatterer size imaging, a broader frequency range provides more information on frequency-dependent backscatter, and therefore, generally more accurate size estimates. Elevational compounding, which can significantly reduce the large statistical fluctuations associated with parametric imaging, becomes readily available with a 2D array. In this work, we show phantom and in vivo breast tumor scatterer size image results using a prototype 2D CMUT transducer (9 MHz center frequency) attached to a clinical scanner. A uniform phantom with two 1 cm diameter spherical inclusions of slightly smaller scatterer size was submerged in oil and scanned by both the 2D CMUT and a conventional piezoelectric linear array transducer. The attenuation and scatterer sizes of the sample were estimated using a reference phantom method. RF correlation analysis was performed using the data acquired by both transducers. The 2D CMUT results indicate that at a 2 cm depth (near the transmit focus for both transducers) the correlation coefficient reduced to less than 1/e for 0.2 mm lateral or 0.25 mm elevational separation between acoustic scanlines. For the conventional array this level of decorrelation requires a 0.3 mm lateral or 0.75 mm elevational translation. Angular and/or elevational compounding is used to reduce the variance of scatterer size estimates. The 2D array transducer acquired RF signals from 140 planes over a 2.8 cm elevational direction. If no elevational compounding is used, the fractional standard deviation of the size estimates is about 12% of the mean size estimate for both the spherical inclusion and the background. Elevational compounding of 11 adjacent planes reduces it to 7% for both media. Using an experimentally estimated attenuation of 0.6 dB cm(-1) MHz(-1), scatterer size estimates for an in vivo breast tumor also demonstrate improvements using elevational compounding with data from the 2D CMUT transducer.

Acoustic hemostasis of porcine superficial femoral artery: Simulation and in-vivo experimental studies

In-vivo focused ultrasound studies were computationally simulated and conducted experimentally with the aim of occluding porcine superficial femoral arteries (SFA) via thermal coagulation. A multi-array HIFU applicator was used which electronically scanned multiple beam foci around the target point. The spatio-temporally averaged acoustic and temperature fields were simulated in a fluid dynamics and acousto-thermal finite element model with representative tissue fields, including muscle, vessel and blood. Simulations showed that with an acoustic power of 200W and a dose time of 60s, perivascular tissue reached 91°C; and yet blood reached a maximum 59°C, below the coagulation objective for this dose regime (75°C). Per simulations, acoustic-streaming induced velocity in blood reached 6.1cm/s. In in-vivo experiments, several arteries were treated. As simulated, thermal lesions were observed in muscle surrounding SFA in all cases. In dosing limited to 30 to 60 seconds, it required 257W to provide occlusion (o...

Thermal efficiency in sonotherapy array design

The use of ultrasound for therapeutic applications involving innovative drug delivery methodologies is a promising area of research to enhance the effectiveness of drug treatment to treat a wide range of diseases, including cancer, peripheral vascular disease, and stroke. Rather than use destructive heating, we have designed and built a family of multi-functional arrays which can ultrasonically identify a target tissue and produce mild heating within this specific tissue site for activated delivery of drug-encapsulated vehicles. These triple array probes are truly multifunctional, operating on a standard commercial imaging system. As sonotherapeutic devices, however, the internal heating and heat dissipation pathways are a concern for design optimization. We have compared three different triple-array probe designs for thermal efficiency and heat transfer characteristics. Each of these multifunctional arrays are comprised of a single center array row of 128 elements operating at 5.3 MHz for imaging, and two 1.5 MHz, 64 element outer arrays operated in parallel for sonotherapy. The laboratory verified KLM model for the low frequency array pair in each probe design has been used to derive estimates of array transmission power and efficiency. Using the key parameters of each design, we can determine the array heat source function and apply analytical expressions to explain the heat dissipation pathways in the probe itself. Our analytical techniques use simplifying assumptions and include the use of both equivalent lumped element thermal circuits for the transducer front port path, and a solution of the PDE heat equation for transient conduction with constant surface heat flux boundary conditions at the transducer backing. The metalized traces of the flex circuits act as the third heat escape pathway. The multifunctional array probes can be used to deliver up to 5 Watts of total acoustic power in mild hyperthermia experiments with small animals. Our analytical expressions have been verified with temperature measurements made in the array backing material and on the array surface. Our early design, the G3, has a triple layer array stack and flex circuit interface connections to support these layers; a later design, the G4, has only a single layer array piezoceramic but has an optimized front port for heat dissipation. The G5 has a further optimized front port and changes in array interconnects. These three probe designs have produced very different thermal dissipation power path distributions; the front, back and flex trace heat path distributions for the three are a) 16%, 2%, 82%, b) 42%, 7%, 51%, and c) 86%, 8%, 6% for the G3, G4, and G5 designs respectively. These results can be directly related to optimized design features which improve the heat routing in sonotherapy array devices.

Acoustic hemostasis device for automated treatment of bleeding in limbs

A research prototype automated image-guided acoustic hemostasis system for treatment of deep bleeding was developed and tested in limb phantoms. The system incorporated a flexible, conformal acoustic applicator cuff. Electronically steered and focused therapeutic arrays (Tx) populated the cuff to enable dosing from multiple Txs simultaneously. Similarly, multiple imaging arrays (Ix) were deployed on the cuff to enable 3D compounded images for targeting and treatment monitoring. To affect a lightweight cuff, highly integrated Tx electrical circuitry was implemented, fabric and lightweight structural materials were used, and components were minimized. Novel cuff and Ix and Tx mechanical registration approaches were used to insure targeting accuracy. Two-step automation was implemented: 1) targeting (3D image volume acquisition and stitching, Power and Pulsed Wave Doppler automated bleeder detection, identification of bone, followed by closed-loop iterative Tx beam targeting), and 2) automated dosing (auto-selection of arrays and Tx dosing parameters, power initiation and then monitoring by acoustic thermometry for power shut-off). In final testing the device automatically detected 65% of all bleeders (with various bleeder flow rates). Accurate targeting was achieved in HIFU phantoms with end-dose (30 sec) temperature rise reaching the desired 33-58°C. Automated closed-loop targeting and treatment was demonstrated in separate phantoms.A research prototype automated image-guided acoustic hemostasis system for treatment of deep bleeding was developed and tested in limb phantoms. The system incorporated a flexible, conformal acoustic applicator cuff. Electronically steered and focused therapeutic arrays (Tx) populated the cuff to enable dosing from multiple Txs simultaneously. Similarly, multiple imaging arrays (Ix) were deployed on the cuff to enable 3D compounded images for targeting and treatment monitoring. To affect a lightweight cuff, highly integrated Tx electrical circuitry was implemented, fabric and lightweight structural materials were used, and components were minimized. Novel cuff and Ix and Tx mechanical registration approaches were used to insure targeting accuracy. Two-step automation was implemented: 1) targeting (3D image volume acquisition and stitching, Power and Pulsed Wave Doppler automated bleeder detection, identification of bone, followed by closed-loop iterative Tx beam targeting), and 2) automated dosing (auto-...