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Low-intensity pulsed ultrasound (LIPUS) accelerates fracture healing by stimulating the production of bone callus and the mineralization process. This study compared a novel bimodal acoustic signal (BMAS) device for bone fracture healing to a clinical LIPUS system (EXOGEN; Bioventus, Durham, NC, USA). Thirty rabbits underwent a bilateral fibular osteotomy. Each rabbits' legs were randomized to receive 20-min treatment daily for 18 days with BMAS or LIPUS. The latter utilizes a longitudinal ultrasonic mode only, while the former employs ultrasound-induced shear stress to promote bone formation. Power Doppler imaging (PDI) was acquired days 0, 2, 4, 7, 11, 14, and 18 post-surgery to monitor treatment response and quantified off-line. X-rays were acquired to evaluate fractures on days 0, 14, 18, and 21. Seventeen rabbits completed the study and were euthanized day 21 post-surgery. The fibulae were analyzed to determine maximum torque, initial torsional stiffness, and angular displacement at failure. ANOVAs and paired t-tests were used to compare pair-wise outcome variables for the two treatment modes on a per rabbit basis. The BMAS system induced better fracture healing with greater stiffness (BMAS 0.21 ± 0.19 versus LIPUS 0.16 ± 0.19 [Formula: see text]cm/°, p = 0.050 ) and maximum torque (BMAS 7.84 ± 5.55 versus LIPUS 6.26 ± 3.46 [Formula: see text]cm, p = 0.022 ) than the LIPUS system. Quantitative PDI assessments showed a higher amount of vascularity with LIPUS than BMAS on days 4 and 18 ( ). In conclusion, the novel BMAS technique achieved better bone fracture healing response than the current Food and Drug Administration (FDA)-approved LIPUS system.

Ultrasound (US) accelerates healing by stimulating the production of bone callus and the process of mineralization. A US system (EXOGEN; Bioventus, Durham, NC, USA) using low intensity pulsed ultrasound (LIPUS) and this principle is FDA-approved. This study analyzed the effectiveness of a novel bimodal acoustic signal (BMAS) for bone fracture healing compared to the clinically used LIPUS system in an animal model. Seventeen mature white New Zealand female rabbits, underwent a bilateral fibula osteotomy as part of an IACUC-approved protocol. Afterwards, each rabbits’ legs were randomized to receive 20 minutes treatment daily for 18 days with BMAS or EXOGEN. The latter utilizes a longitudinal ultrasonic mode only, while the former employs US-induced shear stress to promote bone formation. Power Doppler imaging (PDI) was acquired days 0, 2, 4, 7, 11, 14 and 18 post-surgery to monitor treatment response and local inflammation. Images were analyzed off-line using ImageJ (NIH, Bethesda, MD, USA) for amount and intensity of flow. X-rays were acquired to evaluate fractures on days 0, 14, 18 and 21 post-surgery. Rabbits were euthanized day 21 post-surgery, the legs were extracted and their fibulas were analyzed with an electromechanical device to determine maximum torque, initial torsional stiffness and angular displacement at failure. The legs also underwent □ CT DEXA analysis to determine the ratio of bone mineral density (BMD) or bone mineral content (BMC) values at the fracture level over normal bone values. ANOVAs and paired t-tests were used to compare pairwise outcome variables for the 2 treatment modes on a per rabbit basis. The BMAS system induced better fracture healing with greater stiffness (0.042 ± 0.099 Ncm/deg, p = 0.050) and torque (1.574 ± 2.953 Ncm, p = 0.022) at the fracture sites than the LIPUS (EXOGEN) system. Quantitative PDI assessments showed a higher relative amount of vascularity (i.e., difference in pixel counts) with LIPUS (EXOGEN) than BMAS on days 4 and 18 (p 0.25. The novel BMAS technique achieved better bone fracture healing response than the current FDA-approved LIPUS (EXOGEN) system.

Small tears in tendons are a common occurrence in athletes and others involved in strenuous physical activity. Natural healing in damaged tendons can result in disordered regrowth of the underlying collagen matrix of the tendon. These disordered regions are weaker than surrounding ordered regions of normal tendon and are prone to re-injury. Multiple cycles of injury and repair can lead to chronic tendinosis. Current treatment options either are invasive or are relatively ineffective in tendinosis without calcifications. High-intensity focused ultrasound (HIFU) has the potential to treat tendinosis noninvasively. HIFU ablation of tendons is based on a currently-used surgical analog, viz., needle tenotomy. This study tested the ability of HIFU beams to ablate bovine tendons ex vivo. Two ex vivo animal models were employed: a bare bovine Achilles tendon (deep digital flexor) on an acoustically absorbent rubber pad, and a layered model (chicken breast proximal, bovine Achilles tendon central and a glass plate distal to the transducer). The bare-tendon model enables examination of lesion formation under simple, ideal conditions; the layered model enables detection of possible damage to intervening soft tissue and consideration of the possibly confounding effects of distal bone. In both models, the tissues were degassed in normal phosphate-buffered saline. The bare tendon was brought to 23 degrees C or 37 degrees C before insonification; the layered model was brought to 37 degrees C before insonification. The annular array therapy transducer had an outer diameter of 33 mm, a focal length of 35 mm and a 14-mm diameter central hole to admit a confocal diagnostic transducer. The therapy transducer was excited with a continuous sinusoidal wave at 5.25 MHz to produce nominal in situ intensities from 0.23-2.6 kW/cm(2). Insonification times varied from 2-10 s. The focus was set over the range from the proximal tendon surface to 7 mm deep. The angle of incidence ranged from 0 degrees (normal to the tissue surface) to 15 degrees . After insonification, tendons were dissected and photographed, and the dimensions of the lesions were measured. Transmission electron micrographs were obtained from treated and untreated tissue regions. Insonification produced lesions that mimicked the shape of the focal region. When lesions were produced below the proximal tendon surface, no apparent damage to overlying soft tissue was apparent. The low intensities and short durations required for consistent lesion formation, and the relative insensitivity of ablation to small variations in the angle of incidence, highlight the potential of HIFU as a noninvasive treatment option for chronic tendinosis.

Publications in therapeutic ultrasound have been growing exponentially for the past four decades, n = 2 exp((t-1970)/6), R² = 0.965, and reached approximately 1440 papers in 2011. Adoption of new International Electrotechnical Commission standards by regulatory agencies such as the United States Food and Drug Administration will enable more rapid approval of devices and therefore more clinical applications. Thus the exponential growth is likely to continue with a predicted output of 3600 papers by 2015. In order to serve this growing demand, the Journal of Therapeutic Ultrasound (JTU) has been launched. JTU is an online, open access journal designed to accelerate the adoption of focused ultrasound.

Objective. This study evaluated variables relevant to creating myocardial lesions using high-intensity focused ultrasound (HIFU). Without an effective means of tracking heart motion, lesion formation in the moving ventricle can be accomplished by intermittent delivery of HIFU energy synchronized by electrocardiographic triggering. In anticipation of future clinical applications, multiple lesions were created by brief HIFU pulses in calf myocardial tissue ex vivo. Methods. Experiments used f-number 1.1 spherical cap HIFU transducers operating near 5 MHz with in situ spatial average intensities of 13 and 7.4 kW/cm 2 at corresponding depths of 10 and 25 mm in the tissue. The distance from the HIFU transducer to the tissue surface was measured with a 7.5-MHz A-mode transducer coaxial and confocal with the HIFU transducer. After exposures, fresh, unstained tissue was dissected to measure visible lesion length and width. Lesion dimensions were plotted as functions of pulse parameters, cardiac structure, tissue temperature, and focal depth. Results. Lesion size in ex vivo tissue depended strongly on the total exposure time but did not depend strongly on pulse duration. Lesion width depended strongly on the pulse-to-pulse interval, and lesion width and length depended strongly on the initial tissue temperature. Conclusions. High-intensity focused ultrasound creates well-demarcated lesions in ex vivo cardiac muscle without damaging intervening or distal tissue. These initial studies suggest that HIFU offers an effective, noninvasive method for ablating myocardial tissues to treat several important cardiac diseases.

Spectral parameter imaging in both the fundamental and harmonic of backscattered radio-frequency (RF) data were used for immediate visualization of high-intensity focused ultrasound (HIFU) lesion sites. A focused 5-MHz HIFU transducer with a coaxial 9-MHz focused single-element diagnostic transducer was used to create and scan lesions in chicken breast and freshly excised rabbit liver. B-mode images derived from the backscattered RF signal envelope were compared with midband fit (MBF) spectral parameter images in the fundamental (9-MHz) and harmonic (18-MHz) bands of the diagnostic probe. Images of HIFU-induced lesions derived from the MBF to the calibrated spectrum showed improved contrast ( 3 dB) of tumor margins versus surround compared with images produced from the conventional signal envelope. MBF parameter images produced from the harmonic band showed higher contrast in attenuated structures (core, shadow) compared with either the conventional envelope (3.3 dB core; 11.6 dB shadow) or MBF images of the fundamental band (4.4 dB core; 7.4 dB shadow). The gradient between the lesion and surround was 3.4 dB/mm, 6.9 dB/mm and 17.2 dB/mm for B-mode, MBF-fundamental mode and MBF-harmonic mode, respectively. Images of threshold and "popcorn" lesions produced in freshly excised rabbit liver were most easily visualized and boundaries best- defined using MBF-harmonic mode. (E-mail: rsilverman@rrinyc.org © 2006 World Federation for Ultrasound in Medicine & Biology.

The potential therapeutic uses of ultrasound energy in cardiac disease have not been extensively studied. We have developed a means to deliver high-intensity focused ultrasound (HIFU) to myocardial tissue. Unlike other therapy modalities such as radiofrequency catheter ablation, this system has the advantages of not requiring direct tissue contact and the ability to focus intense energy within a small volume.Sections of left and right ventricles from freshly excised canine hearts were treated in vitro with HIFU pulses. Lesions were created using 1-second HIFU pulses with ultrasonic powers ranging from 19.8 to 45.8 W.There was a dose-response relationship between the applied HIFU energy and lesion size (r = 0.70, P.001). Myocardial lesion formation with HIFU was also performed in vivo in a canine open-chest beating heart model. With 200-millisecond HIFU pulses gated to the electrocardiogram, focal myocardial lesions were created ranging in length from 2 to 6 mm depending on the dose used. Furthermore, both in vitro and in vivo, focal lesions were successfully formed in the midmyocardial wall that spared both the endocardial and epicardial surfaces.HIFU is a novel means to create focal myocardial lesions without direct tissue contact. HIFU energy delivery can be gated to the electrocardiogram in an in vivo model, and lesions can be formed intramyocardially. Further application of this technology may prove to be useful for the ablation of myocardial lesions such as arrhythmogenic foci and the hypertrophic ventricular septum in hypertrophic cardiomyopathy. The potential therapeutic uses of ultrasound energy in cardiac diseases have not been well studied. We tested a novel system to deliver high-intensity focused ultrasound energy in vitro and in vivo to canine myocardial samples without direct contact with the target tissue. Focal myocardial lesions were formed in a dose-dependent manner, and myocardial lesions were created. This technology may prove useful for ablation of focal intramyocardial lesions such as arrhythmogenic foci and the hypertrophic left ventricular septum in hypertrophic cardiomyopathy.

The purpose of this study was to evaluate the possibility of using high-intensity focused ultrasound (US), or HIFU, to create lesions in cardiac valves in vitro. Calf mitral valves and aortic valves were examined. Focused US energy was applied with an operating frequency of 4.67 MHz at a nominal acoustic power of 58 W for 0.2, 0.3 and 0.4 s at 4-s intervals. Mitral valve perforation was achieved with 20.8 3.7 exposures of 0.2 s, 15.4 2.1 exposures of 0.3 s or 11.2 2.3 exposures of 0.4 s. Aortic valve perforation was achieved with 13.3 2.4 exposures of 0.2 s, 10.3 2.2 exposures of 0.3 s or 8.4 1.8 exposures of 0.4 s. The mean diameter of the perforated area was 1.09 0.11 mm. The lesions were slightly discolored and coagulation of tissue around the perforation was observed. HIFU was successful in perforating cardiac valves. With further refinement, HIFU may prove useful for valvulotomy or valvuloplasty. (E-mail: otsukaryo@aol.com) © 2005 World Federation for Ultrasound in Medicine & Biology.

The Journal of Therapeutic Ultrasound has been established to provide an open access, online venue for the exponentially growing body of work in biomedical ultrasound therapy.

Among current modalities, ultrasound uniquely offers both millisecond and millimeter accuracy in noninvasively stimulating brain tissue. In addition, by sweeping the ultrasound beam within the refractory period of the neuronal tissue, ultrasonic neuromodulation can be adapted to target extended or multiply connected regions with quasi-simultaneity. Towards the development of this safe brain stimulus technique, the response of rat hippocampal cultures to ultrasound was investigated. Hippocampal slices, 0.4-mm thick, were obtained from 8-day old Sprague Dawley rats and cultured for 6 days. The in vitro cultures were exposed to multiple 100-ms 4.04-MHz ultrasound pulses from a 42-mm diameter, 90-mm spherical cap transducer. Peak pressure ranged from 0 through about 77 kPa. Responses in the form of electrical potentials from a sixty channel electrode array were digitized and recorded. The DG and CA1 regions of the hippocampus exhibited similar ultrasonically-evoked field potentials.

A new signal interrogation concept, based on Synthetic Structural Imaging (SSI) physics, has been developed to guide therapies. The SSI method was previously successful in radar and sonar imaging; here it is demonstrated for acoustic scattering from penetrable biological targets. Operating at ultrasonic frequencies of several hundred kilohertz, SSI trades the higher resolution of typical B-mode ultrasound imaging for a significantly stronger correlation to target shape and volume, which are among the primary tissue classifiers. Tissue phantom models were fabricated with embedded spheroidal inclusions ranging from 2.41 mm through 6.3 mm in diameter. The phantom medium was 10 wt% porcine gelatin and the inclusions were 28 wt% porcine gelatin. The inclusion dimensions were measured with calipers. The phantom was interrogated with two impulse-excited Panametrics transducers: a model V301 with a peak frequency of 0.50 MHz and a −6 dB bandwidth of 81%, and a model V314 with a peak frequency of 0.99 MHz and a −6 dB bandwidth of 77%. The backscattered RF data were digitized, recorded, and digitally bandpass-filtered. The experimental profile functions were computed. Volumes were estimated by integrating the experimental profile functions. SSI-determined volume ratios were demonstrated to be within 7% to 18% of caliper-determined volume ratios.

Direct and safe manipulation of neurons by external means is an increasingly studied therapeutic modality with the potential to treat many neurological diseases. Anticipating such future applications, we investigated reversible bioeffects of very low dose focused ultrasound on neuronal cell morphology and function in vitro. To test morphological changes, undifferentiated PC12 cells were serum‐cultured. The culture plates were placed on an inverted optical microscope. An f/1.1 ultrasound transducer with a water‐filled coupling cone was focused on the culture and excited with 30‐ms 4.67‐MHz 100‐kPa pulses. To test functional changes, rat hippocampal slices were cultured and individually transferred to the well of a 60‐channel multi electrode array. An f/2.1 ultrasound transducer with a water‐filled coupling cone was focused on a culture and excited with 100‐μs 4.04‐MHz 77‐kPa pulses. The culture was stimulated before and after the ultrasonic stimulus with a 100‐μs 100‐μA biphasic electrical stimulus. Optica...

Mitral regurgitation, when it arises from functional restriction of mitral leaflet closure, can be relieved by surgical cutting of the mitral tendineae chordae. We hypothesized that high intensity focused ultrasound (HIFU) might be useful as a noninvasive extracorporeal technique for cutting mitral chordae. As a pilot study to test this hypothesis, we examined the in vitro feasibility of using HIFU to cut calf mitral chordae with diameters from 0.2 to 1.6 mm. Sixty-seven percent of chordae were completely cut with HIFU, operated at 4.67 MHz and 45 W acoustic power, with up to 120 pulses of 0.3-s duration at 2-s intervals. Forty-five percent were completely cut when the pulse duration was reduced to 0.2 s. The average diameter of those chordae, which were completely cut, was significantly smaller than that of incompletely cut chordae (0.59 +/- 0.30 versus 1.14 +/- 0.30 mm with a pulse duration of 0.2 s, p < 0.0001; 0.68 +/- 0.29 versus 1.32 +/- 0.20 mm with a pulse duration of 0.3 s, p < 0.0001). For each pulse duration, the number of pulses required for complete cutting exhibited a strong positive correlation with the chordae diameter. In conclusion, in vitro feasibility of mitral chordal cutting by HIFU depended on the diameter of chordae but was controllable by HIFU settings. (E-mail: abeyukio@aol.com).

OBJECTIVE: HIFU is a promising technique for treating cardiac ventricular diseases such as sustained ventricular tachycardia. Ablations can potentially destroy arrhythmogenic foci and block reentrant circuits. Towards this end, we have learned to control HIFU lesions in the canine model in vivo. METHODS: Experiment — Thoracotomies were performed on anesthetized dogs, following IACUC guidelines. In this open‐chest configuration, a polyethylene water‐filled bag was coupled to the myocardium with degassed ultrasound gel. The transducer was lowered into the water. Ventricular locations were targeted and insonified with multiple 200‐ms HIFU bursts of 60‐W acoustic power; the bursts were triggered with the electrocardiogram QRS complex. The therapeutic transducer was a 35‐mm focal length, 33‐mm diameter PZT annular array, excited at 5.25 MHz. Its −3dB focal region dimensions were 2.5 mm axially and 0.3 mm transversely. A confocal diagnostic transducer was used for aiming and for recording backscattered radiofrequency ultrasound data. Theory — A comprehensive acoustic model has been developed. Individual modules numerically simulate physical processes such as ultrasound beam propagation, energy transfer, and heat flow within tissue. One set of modules simulates HIFU ablation in moving tissue. Tissue motion was obtained from digitized B‐mode videos of transverse cross sections of a beating canine heart. Epicardial and endocardial surface positions were extracted from the video frames. Additional simulations of static tissue compared linear and nonlinear propagation models. RESULTS: Significant agreement between simulated and measured lesion sizes and between linear and nonlinear propagation models was demonstrated.

Background High-intensity focused ultrasound (HIFU) produces immediate focal lesions without direct tissue contact. Previously, we reported the HIFU potential for cardiac ablation. The purpose of this study was to evaluate the possibility of myocardial ablation in the left ventricle of beating dog hearts with monitoring by 2-dimensional echocardiography. Methods The operating frequency and the acoustic intensity were 5.25 MHz and 23 kW/cm 2 , and the focal length and diameter were 3.3 mm axial and 0.37 mm wide at a distance of 35 mm from the transducer. Three dogs underwent a left-sided thoracotomy. The right ventricular surface was coupled with the transducer. The timing of the HIFU exposure was set during the early systolic phase using an electrocardiographic triggering system. The focal point was set in the left ventricular septum using 2-dimensional echocardiography mounted in the HIFU transducer. Ultrasound energy was delivered for 0.2 seconds. For each dog, we created 18 lesions. Exposures were performed 20, 30, or 40 times. Lesion size was assessed by manually measuring its length and width. Results All lesions except one were clearly visible. The histologic lesion area was 18.7 ± 8.3, 26.3 ± 8.7, and 35.5 ± 15.7 mm 2 (20, 30, and 40 times, respectively). The intraclass correlation coefficients were found to be 0.72, 0.63, 0.75, and 0.73 for lesion length, width, area, and depth, respectively. Conclusion HIFU can be used to create targeted, well-demarcated thermal lesions in the ventricular septum myocardium during cardiac contraction.

HIFU dose curves (lesion size vs. exposure parameters) exhibit scatter because of local variations in the acoustic properties of tissue. Therefore, clinical applications of HIFU, such as cardiac and cancer ablation, will benefit from the ability to distinguish treated from normal tissue, which can provide the surgeon with lesion monitoring. However, HIFU lesions, especially protein‐denaturing lesions (PDLs), may be difficult to visualize with conventional B‐mode ultrasound. In this study, spectrum analysis of backscattered radiofrequency (RF) ultrasound was successful in imaging lesions. HIFU lesions were formed at 5 MHz for various intensities and durations in model tissues including degassed chicken breast in vitro, fresh rabbit liver ex vivo, and canine cardiac left ventricle in vivo. The tissues were scanned pre‐ and post‐exposure using confocal array and single‐element diagnostic probes incorporated into the HIFU transducer assembly. The diagnostic probes were excited with a monocycle pulse under conditions previously shown to generate a second harmonic comparable in amplitude to the fundamental, and RF echo‐signal data were recorded. In an alternate set, the therapy and diagnostic transducers were operated pitch‐catch, with the therapy transducer sending out a series of 0.4 ms pulses and the diagnostic transducer in passive receive mode. Spectrum analysis of the RF data was performed separately on first (fundamental) and second harmonic frequency bands. Linear regression fits to spectra computed for sliding regions‐of‐interest yielded 3 parameters: midband fit (integrated backscatter), y‐intercept and slope; grayscale images were produced for each parameter. Differences among the B‐mode and parameter images, and between the lesion site and adjacent untreated tissues, were characterized statistically. The results indicate that midband fit images of both the fundamental and harmonic offer improved contrast and lateral resolution compared to conventional images. PDLs and bubbly lesions that are not clearly visible in B‐mode images can be imaged with harmonic band spectrum analysis.

The Sonocare CST‐100 Therapeutic Ultrasound System, designed for the treatment of glaucoma, was developed in the 1980s and became the first high intensity focused ultrasound (HIFU) device to receive Food and Drug Administration approval. The system arose from studies done by F.L. Lizzi, Eng.Sc.D., of Riverside Research Institute and D.J. Coleman, M.D., of Cornell Medical Center/New York Hospital on the safety of ultrasound diagnosis of the eye. As safety limits were probed, therapeutic regimes were discovered. Optimization of operational parameters, clinical experience, and engineering design came together through a spin‐off company, Sonocare, Inc., formed to produce and market the ophthalmic device. Various precedents were set during the approval process, including the acceptance by the FDA of radiation momentum imparted to an absorber as a measure of acoustic power. Many devices were sold, but the laser industry, grandfathered into the therapeutic field, eventually out‐marketed Sonocare. The CST‐100 remains as a model of elegant industrial design, and existing units are used daily in HIFU laboratory experiments.

A versatile biomedical ultrasound system has been developed and tested. The system controls and monitors high‐intensity focused ultrasound (HIFU) exposures designed to produce therapeutic tissue lesions primarily by thermal phenomena. The system is used with custom HIFU transducer arrays that contain central diagnostic transducer arrays. The diagnostic and visualization functions are performed using a subsystem that provides full digital control over high‐resolution diagnostic ultrasound arrays. Custom software controls all aspects of the imaging (e.g., electronic focusing and frame rates) with scripts and a graphical user interface. The HIFU transducer is excited using a 16‐channel power amplifier controlled by a digital subsystem and waveform synthesizers. Software operator control is also provided for desired HIFU exposure parameters (apodization, frequency, time duration, focal length, intensity) and a variety of synchronous excitation modes for the HIFU and diagnostic arrays.

The potential for cardiac applications of HIFU remains largely unexplored. In order to create reproducible lesions in a beating heart, it is necessary to maintain focusing at a certain position within moving myocardial tissue. One technique is to use multiple short HIFU exposures (0.2 s) and to synchronize them with an EKG signal and respiration. In order to investigate the interaction of HIFU exposures and cardiac tissues, a series of in‐vitro experiments was conducted. The left ventricular free wall (LVFW) of calf hearts were cut into 4‐cm cubes, degassed in phosphate buffer saline (PBS), and heated to 37C. Several transducers were employed. Most experiments used a 33‐mm diameter spherical‐cap transducer with focal length of 35 mm, operated at a frequency of 5.075 MHz and a focused intensity of 13 kW/cm2 (in‐situ spatial average over the half‐power points of the focused beam). The transducer was coupled to the LVFW using degassed PBS. First, the effects of pericardial fat, focal depth, and temperature on lesion size were individually evaluated. We compared the effect of different time pulse duration (0.2 s and 0.3 s) and number of applied pulses. Dimensions of all lesions were measured by visual examination of the fresh, unstained tissue. Histopathological examination of the lesions was also performed.

A dual-transducer system was used to test concepts for on-line guidance and lesion monitoring during ultrasound therapy. The system used a spherical-cap therapy transducer with a central, A-mode transducer. Three operational modes were successfully tested in in-vitro liver specimens. Mode 1 senses in-situ therapy-beam harmonics that affect absorption and heating. The therapy transducer emits a 2 /spl mu/s pulse at the same amplitude used in therapy; echoes from this pulse are received with the A-mode transducer and digitally filtered to produce A-scans at the therapy frequency and its harmonics. Mode 2 detects lesions by virtue of their increased stiffness. A 1-ms therapy-transducer pulse produces radiation force and internal tissue motion that is tracked by cross-correlating sequential A-scans. The procedure is repeated after therapy to detect motion changes due to formed lesions. Mode 3 uses the A-mode transducer (pulse-echo) to sense lesions with increased attenuation and scattering using sliding-window spectrum analysis.

This report describes a monitoring technique for high-intensity focused ultrasound (US), or HIFU, lesions, including protein-denaturing lesions (PDLs) and those made for noninvasive cardiac therapy and tumor treatment in the eye, liver and other organs. Designed to sense the increased stiffness of a HIFU lesion, this technique uniquely utilizes the radiation force of the therapeutic US beam as an elastographic push to detect relative stiffness changes. Feasibility was demonstrated with computer simulations (treating acoustically induced displacements, concomitant heating, and US displacement-estimation algorithms) and pilot in vitro experimental studies, which agree qualitatively in differentiating HIFU lesions from normal tissue. Detectable motion can be induced by a single 5 ms push with temperatures well below those needed to form a lesion. Conversely, because the characteristic heat diffusion time is much longer than the characteristic relaxation time following a push, properly timed multiple therapy pulses will form lesions while providing precise control during therapy. (E-mail: muratore@rrinyc.org) © 2003 World Federation for Ultrasound in Medicine & Biology.

Probabilistic modelling of continuous current sources is applied to the analysis of MEG signals generated by current dipoles implanted in the head of a living human subject. Estimates of the distribution of activity within a circular disk are obtained from signals generated by a single implanted dipole and by a pair of simultaneously active implanted dipoles. The orientation and depth of the disc is determined in advance from the experimental geometry and the measurements. The resulting reconstructions constitute the first in vivo validation of distributed source imaging; they provide a complementary test to earlier works using computer generated data and tests using point source analysis of signals generated by a single implanted dipole. In this work we provide a literal test of spatial resolution by resolving two nearby point-like sources. Temporal resolution is addressed in a de facto manner by imaging at one millisecond intervals. Computer simulations, with controlled amount of noise, are used to demonstrate the robustness of the results, and show the interplay between high spatial accuracy and noise insensitivity.

Magnetoencephalography (MEG) is a new, noninvasive functional test equivalent to EEG. It has been used to localize the sources of evoked responses and interictal and ictal epileptiform discharges and to study patients with psychiatric illnesses, cerebrovascular accidents, and migraine. In epilepsy research, it is hoped that MEG will provide information similar to that yielded by depth or subdural electrode recording, or that the combination of these methods will provide more information than either one alone. The application of MEG appears to be widening, although it is not yet a routine clinical diagnostic tool. The utility of MEG is limited by technological problems, but new and more efficient systems are becoming available. Within several years, advances in the technology and understanding of MEG may modify the course of its application.

To understand and prevent brain injuries from head trauma, researchers study mechanically stressed neuronal tissue. To anticipate future application of controllable ultrasonic in‐vivo stress, we investigated the effects of acoustic radiation force on in‐vitro PC12 cells. Undifferentiated PC12 cells were serum‐cultured in DMEM/F12 on poly‐L‐lysine‐coated polystyrene. Some cultures were DAPI stained. The culture plates were placed on an inverted phase‐contrast microscope. An f/1.1 ultrasound transducer with a water‐filled coupling cone was focused on the culture at a 45‐degree angle‐of‐incidence, and excited with 30‐ms 4.7‐MHz pulses. Acoustic power was 8 W, and peak pressure was estimated at 300 kPa. Digital images were recorded before, during, and after insonification. Incident‐light and fluorescence images revealed three populations: cells that were stationary (apparently outside the effective force field region), cells that elongated about 2 μm under radiation force and returned to approximately their o...

Diagnostic ultrasound is used to measure distance from a transducer to selected tissue structure. In one arrangement, the focal point of a high intensity focused ultrasound transducer is adjusted in accordance with measured distance to the selected tissue structure. In a second arrangement a transducer transport apparatus moves a transducer to maintain a selected distance from tissue structure.

High‐intensity focused ultrasound (HIFU) (4.5–7.5 MHz) was used to form lesions in cardiac tissue, with an ultimate objective of treating conditions such as hypertrophic cardiomyopathy and ventricular tachycardia. Ultrasound attenuation coefficients were experimentally determined in vitro for calf myocardial tissue, both muscle and pericardial fat. These coefficients were employed in computational models of linear beam propagation, tissue heating profiles and thermal lesion formation for a variety of focused transducers. Modeling was performed for continuous and pulsed exposures. These models suggested initial power levels and exposure durations for in vitro experiments on calf ventricles and septa and ex vivo experiments on canine whole hearts. Repeatability of lesion size and placement was studied as power and exposure parameters varied around the initial values. With these experimental results, power and exposure parameters were selected to create lesions in vivo in canine ventricles and septa in open‐...

The potential for cardiac applications of HIFU remains unexamined. In order to create reproducible lesions in a beating heart, it is necessary to maintain focusing at a certain position within moving myocardial tissue. One technique is to use multiple short HIFU exposures (0.2 s) and synchronize them with an EKG signal and respiration. The left ventricular free wall (LVFW) of calf hearts were cut into 4‐cm cubes, degassed in phosphate buffer saline (PBS), and heated to 37 °C. An 80‐mm‐diam spherical‐cap transducer with a focus of 90 mm was operated at a frequency of 4.67 MHz and a nominal focal point intensity of 26.9 kW/cm2. The transducer was coupled to the LVFW using degassed PBS. First, the effect of pericardial fat, focal depth, and temperature on lesion size was individually evaluated. Then the 0.2‐s HIFU exposure was applied 10 to 30 times at 4‐s intervals. The same HIFU transducer was applied to an open‐chest canine LVFW with the same triggering protocol. Dimensions of all lesions were measured by visual examination of the fresh, unstained tissue. A histopathological examination of the lesion was also performed. The in vivo lesions were created in similar size to those in vitro.

Investigations are being conducted to develop a method using motion induced by radiation force to monitor HIFU lesions, by virtue of their increased stiffness. A therapeutic transducer, periodically excited at subthreshold levels, generates the radiation force: a collinear diagnostic transducer monitors the degree and time‐course of induced motion. Lesions are detected by changes in pre‐ and post‐treatment motion patterns. In vitro experiments and computer simulations have been performed to clarify the roles of several phenomena so that optimized systems can be designed for practical on‐line applications. Lesion attenuation has been found to be a key factor since it directly affects radiation force. Lesions with near‐normal attenuation exhibit less motion than normal, because of increased stiffness. Lesions with significantly higher attenuation can exhibit increased motion, due to increased force, but they demonstrate spatial patterns differing from normal. The profile of the push beam was found to affect...

We have developed a dual‐transducer technique to monitor tissue deformation induced by therapeutic ultrasound. The technique is designed to monitor and control therapeutic lesion size and location. Currently, the technique employs a spherical‐cap high‐intensity transducer with a central, co‐linear diagnostic transducer. A‐mode rf echo signals are first acquired using the diagnostic transducer to document pre‐exposure conditions within the target tissue. A short (10 ms) intense exposure is then delivered with the spherical‐cap transducer in order to induce tissue motion by radiation force. A‐mode rf signals are then acquired for 0.2 s. Pre‐ and post‐exposure A‐mode signals are analyzed using correlation processing to determine the extent of induced tissue motion. The time constant associated with return to initial tissue positions is also calculated. These procedures have been applied in vitro to liver specimens using the spherical‐cap transducer to periodically induce motion and to produce thermal lesions...

Antiprotons are presently produced and stored at CERN and Fermilab at a rate of about 10 7 p/s. Efforts are underway to develop transportable storage devices, ‘bottles’, which would store as much as 10 12 antiprotons for months, or years and make the antiprotons available anywhere. A workshop held last year at the RAND Corporation assessed the science and technology of antimatter and the enabling tools. The biomedical potential of antiprotons was discussed and appears to be promising at current antimatter collection capabilities. Two applications have been studied using computer simulations: direct 3-D d E /d x imaging and the treatment of tumors with antiprotons. We discuss antiprotonic imaging and make comparisons with X-ray CT scans. The potential of antiprotons for monitoring precise delivery of radiation as well as treatment will also be discussed.