Feasibility of Using Lateral Mode Coupling Method for a Large Scale Ultrasound Phased Array for Noninvasive Transcranial Therapy

A hemispherical-focused, ultrasound phased array was designed and fabricated using 1372 cylindrical piezoelectric transducers that utilize lateral coupling for noninvasive transcranial therapy. The cylindrical transducers allowed the electrical impedance to be reduced by at least an order of magnitude, such that effective operation could be achieved without electronic matching circuits. In addition, the transducer elements generated the maximum acoustic average surface intensity of $hbox{27 W/cm}^{2}$. The array, driven at the low (306-kHz) or high frequency (840-kHz), achieved excellent focusing through an ex vivo human skull and an adequate beam steering range for clinical brain treatments. It could electronically steer the ultrasound beam over cylindrical volumes of 100-mm in diameter and 60-mm in height at 306 kHz, and 30-mm in diameter and 30-mm in height at 840 kHz. A scanning laser vibrometer was used to investigate the radial and length mode vibrations of the element. The maximum pressure amplitudes through the skull at the geometric focus were predicted to be 5.5 MPa at 306 kHz and 3.7 MPa at 840 kHz for RF power of 1 W on each element. This is the first study demonstrating the feasibility of using cylindrical transducer elements and lateral coupling in construction of ultrasound phased arrays.      

Calibration of water proton chemical shift with temperature for noninvasive temperature imaging during focused ultrasound surgery

Long-standing ulcerative colitis is considered to be a precancerous condition. Therefore, a practical and reliable method is required for monitoring the progress of the disease. Liberation of the S-phase from karyokinesis occurs in DNA amplification and endoreplication, producing nuclei with more than 4 c DNA. The amount of Feulgen DNA was quantified with an image microphotometer in 8 microns sections for interphase nuclei and in 15 microns sections for chromosome division figures (CDFs). Development of ulcerative colitis was investigated in low grade dysplasia (n = 93 cases; score 3-7) and high grade dysplasia (n = 22; score 8-10). Bacterial colitis (n = 34) and invasive adenocarcinoma (n = 26) provided a basis for data interpretation in dysplasia. Lymphocyte nuclei served as an internal DNA standard. CDFs represent a novel type of aberrant 'mitoses'; they are different from and much more frequent than figures with multipolar spindles. Endoreplication began with low grade dysplasia in interphase nuclei as well as with CDFs; it was fully established in high grade dysplasia and carcinoma. Endoreplicated interphase nuclei and CDFs represent an early morphological mosaic of genomic instability. Both characteristics support a reproducible two-level classification of low and high grade dysplasia in ulcerative colitis.     

Design and evaluation of a feedback based phased array system for ultrasound surgery

A driving system has been designed for phased array ultrasound applicators. The system is designed to-operate in the bandwidth 1.2 to 1.8 MHz, with independent channel power control up to 60 W (8 bit resolution) for each array element. To reduce power variation between elements, the system utilizes switching regulators in a feedback loop to automatically adjust the DC supply of a class D/E power converter. This feedback reduces the RF electrical power variation from 20% to 1% into a 16 element array. DC-to-RF efficiencies close to 70% for all power levels eliminates the need for large heat sinks. In addition to power control, each channel may be phase shifted 360 degrees with a minimum of 8 bit resolution. To ensure proper operation while driving ultrasound arrays with varying element sizes, each RF driving channel implements phase feedback such that proper phase of the driving signal is produced either at the amplifier output before the matching circuitry or after the matching circuitry at the transducer face. This feedback has been experimentally shown to increase the focal intensities by 20 to 25% of two tested phased arrays without array calibration using a hydrophone.     

Experimental evaluation of two simple thermal models using hyperthermia in muscle in vivo

The predictions from two simple field equation models for calculating temperature distributions in tissue, namely, the Pennes' bioheat transfer equation (BHTE) and an effective thermal conductivity equation (ETCE), were compared to in vivo experimental temperature measurements made under hyperthermic conditions generated by scanned focused ultrasound. The models were kept simple (i.e. homogenous isotropic properties, no separate blood vessels included) in order to concentrate attention on the predictive abilities of these field equations using a minimum number of free parameters. Simulated results were fitted to the experimental data (multiple, linear temperature profiles in the thigh muscles of greyhound dogs) by minimizing a performance index using a golden section searth. This search determined a value for the single free parameter in each model (blood perfusion in the BHTE, and effective thermal conductivity in the ETCE) which minimized the square error difference between the experimental and simulated temperatures. The results showed that (a) the simple BHTE model could qualitatively reproduce the major features of the temperature patterns seen experimentally better than the ETCE model could, and (b) the simple BHTE model produced better quantitative fits to the experimental data than did the simple ETCE model. In addition, blood perfusion predictions from the BHTE model compared well to measurements done with coloured microspheres. Finally, the experimental results showed that individual, large blood vessels appeared to have a major influence in producing asymmetries in the experimental data in 21% of the measured temperature profiles.     

Trans-skull ultrasound therapy: the feasibility of using image-derived skull thickness information to correct the phase distortion

Recent papers have shown that focused ultrasound therapy may be feasible in the brain through an intact human skull by using phased arrays to correct the phase distortion induced by the skull bone. The hypothesis of this study is that the required phase shifts for the phased array can be calculated from the skull shape and thickness provided by modern imaging techniques. The shape and thickness of a piece of human skull was traced from the serial images and used in a theoretical model to calculate the phase distribution for a phased array. A 76-element phased array was manufactured and used in the tests. The piece of skull and the transducer array were positioned in a waterbath, and the ultrasound field distributions were mapped with and without the phase correction. The image-derived phase correction produced a sharp focus through the skull. These results showed that ultrasound brain therapy may be executed completely noninvasively through an intact skull by using a phased array and the skull thickness information derived from MRI scans.     

Micro-receiver guided transcranial beam steering

A new method for focusing ultrasound energy in brain tissue through the skull is investigated. The procedure is designed for use with a therapeutic transducer array and a small catheter-inserted hydrophone receiver placed in the brain to guide the array's focus. When performed at high-intensity, a focal intensity on the order of several hundred watts per centimeter-squared is achieved, and cells within a target volume are destroyed. The present study tests the feasibility and range of the method using an ex vivo human skull. Acoustic phase information is obtained from the stationary receiver and used to electrically shift the beam to new locations as well as correct for aberrations due to the skull. The method is applied to a 104-element 1.1 MHz array and a 120-element 0.81 MHz array. Using these array configurations, it is determined that the method can reconstruct and steer a focus over a distance of 50 mm. Application of this minimally invasive technique for ultrasound brain therapy and surgery also is investigated in vitro with a 64-element 0.664 MHz hemisphere array designed for transskull surgery. Tissue is placed inside of a skull and a catheter-inserted receiver is inserted into the tissue. A focus intense enough to coagulate the tissue is achieved at a predetermined location 10 mm from the receiver, the maximum distance that this large element array can electronically steer the focus.     

Lateral mode coupling to reduce the electrical impedance of small elements required for high power ultrasound therapy phased arrays

A method that uses lateral coupling to reduce the electrical impedance of small transducer elements in generating ultrasound waves was tested. Cylindrical, radially polled transducer elements were driven at their length resonance frequency. Computer simulation and experimental studies showed that the electrical impedance of the transducer element could be controlled by the cylinder wall thickness, while the operation frequency was determined by the cylinder length. Acoustic intensity (averaged over the cylinder diameter) over 10 W/cm² (a therapeutically relevant intensity) was measured from these elements.     

Modeling of anomalies due to hydrophones in continuous-wave ultrasound fields

Needle and spot-poled membrane hydrophones using polyvinylidene fluoride (PVDF) sensors are widely used for characterization of biomedical ultrasound fields. It is known that, in measurements of continuous-wave (CW) fields, standing waves may be generated between the transducer and the hydrophone, distorting the field and possibly alternating the signal of the hydrophone. This study uses a three-dimensional, full-wave method to computationally simulate the distortion in the CW field caused by needle and membrane hydrophones. The physical model used in simulations is based on the linear time-harmonic wave equation, which therefore neglects the effects of nonlinear wave propagation. The significance of the distortion is examined by comparing fields emitted by 0.5-5.0 MHz planar circular transducers in the absence and presence of the hydrophones. In addition, the effect of the field distortions on the signal of the hydrophones is studied with simulated measurements. The simulations showed an observable standing wave pattern between the source and the needle hydrophone if the diameter of the needle was larger than a half of the wavelength. However, the standing waves had no clear effect on the signal of the hydrophone. The presence of membrane hydrophone in the CW field generated notable standing waves. Furthermore, the standing waves caused a periodic distortion to the signal of the membrane hydrophone.     

Large improvement of the electrical impedance of imaging and high-intensity focused ultrasound (HIFU) phased arrays using multilayer piezoelectric ceramics coupled in lateral mode

With a change in phased-array configuration from one dimension to two, the electrical impedance of the array elements is substantially increased because of their decreased width (w)-to-thickness (t) ratio. The most common way to compensate for this impedance increase is to employ electrical matching circuits at a high cost of fabrication complexity and effort. In this paper, we introduce a multilayer lateral-mode coupling method for phased-array construction. The direct comparison showed that the electrical impedance of a single-layer transducer driven in thickness mode is 1/(n2(1/(w/t))2) times that of an n-layer lateral mode transducer. A large reduction of the electrical impedance showed the impact and benefit of the lateral-mode coupling method. A one-dimensional linear 32-element 770-kHz imaging array and a 42-element 1.45-MHz high-intensity focused ultrasound (HIFU) phased array were fabricated. The averaged electrical impedances of each element were measured to be 58 Ω at the maximum phase angle of -1.2° for the imaging array and 105 Ω at 0° for the HIFU array. The imaging array had a center frequency of 770 kHz with an averaged -6-dB bandwidth of approximately 52%. For the HIFU array, the averaged maximum surface acoustic intensity was measured to be 32.8 W/cm2 before failure.     

Bulk Doping of Millimeter‐Thick Conjugated Polymer Foams for Plastic Thermoelectrics

Foaming of plastics allows for extensive tuning of mechanical and physicochemical properties. Utilizing the foam architecture for plastic semiconductors can be used to improve ingression of external molecular species that govern the operation of organic electronic devices. In case of plastic thermoelectrics, utilizing solid semiconductors with realistic (millimeter (mm)‐thick) dimensions does not permit sequential doping—while sequential doping offers the higher thermoelectric performance compared to other methods—because this doping methodology is diffusion limited. In this work, a fabrication process for poly(3‐hexylthiophene) (P3HT) foams is presented, based on a combination of salt leaching and thermally induced phase separation. The obtained micro‐ and nanoporous architecture permits rapid and uniform doping of mm‐thick foams with 2,3,5,6‐tetrafluoro‐7,7,8,8‐tetracyanoquinodimethane, while thick solid P3HT structures suffer from protracted doping times and a dopant‐depleted central region. Importantly, the thermoelectric performance of a P3HT foam is largely retained when normalized with regard to the quantity of used material.