S. K. Patch

Optimum electromagnetic heating of nanoparticle thermal contrast agents at rf frequencies

Enhanced heating of nanoparticles for applications such as thermoacoustic imaging and therapeutic heat delivery is considered. The optimum electrical conductivity to achieve maximum electromagnetic energy deposition in a given nanoparticle is obtained, with emphasis on rf frequencies, where plasmon resonances associated with negative permittivity are generally not possible. Spheres, coated spheres, nanowires, and carbon nanotubes are considered. In all cases, it is found that relatively small conductivity values (e.g., σ⪡1 S/m for spheres) provide the maximum absorption of rf energy, and thus maximizes heat production in the nanoparticle. Therefore, lossy dielectrics may be a better choice for maximizing nanoparticle heat production than metallic particles.

Measurement of Broadband Temperature-Dependent Ultrasonic Attenuation and Dispersion Using Photoacoustics

The broadband ultrasonic characterization of biological fluids and tissues is important for the continued development and application of high-resolution ultrasound imaging modalities. Here, a photoacoustic technique for the transmission measurement of temperature-dependent ultrasonic attenuation and dispersion is described. The system uses a photoacoustic plane wave source constructed from a polymethylmethacrylate substrate with a thin optically absorbent layer. Broadband ultrasonic waves are generated by illuminating the absorbent layer with nanosecond pulses of laser light. The transmitted ultrasound waves are detected by a planar 7-mum high-finesse Fabry-Perot interferometer. Temperature- induced thickness changes in the Fabry-Perot interferometer are tracked to monitor the sample temperature and maintain the sensor sensitivity. The measured -6-dB bandwidth for the combined source and sensor is 1 to 35 MHz, with an attenuation corrected signal level at 100 MHz of -10 dB. The system is demonstrated through temperature-dependent ultrasound measurements in castor oil and olive oil. Power law attenuation parameters are extracted by fitting the experimental attenuation data to a frequency power law while simultaneously fitting the dispersion data to the corresponding Kramers-Kronig relation. The extracted parameters are compared with other calibration measurements previously reported in the literature.

rf testbed for thermoacoustic tomography

Thermoacoustic signal excitation is a function of intrinsic tissue properties and illuminating electric field. De-ionized (DI) water is a preferred acoustic coupling medium for thermoacoustics because acoustic and electromagnetic waves propagate in DI water with very little loss. We have designed a water-filled testbed propagating a controlled electric field with respect to pulse shape, power, and polarization. Directional coupler line sections permit measurement of incident, reflected, and transmitted powers. Both S-parameters and E(y) measurement show that the electric-field distribution is relatively uniform in testbed. Comparing baseline power measurements to those taken with a test object in place yields power loss in the object, which should correlate to thermoacoustic signal strength. Moreover, power loss--and therefore thermoacoustic computerized tomography signal strength--is sensitive to the orientation of the object to the polarization of the electric field. This testbed will enable quantitative characterization of the thermoacoustic contrast mechanism in ex vivo tissue specimens.

Ex Vivo Thermoacoustic Imaging Over Large Fields of View With 108 MHz Irradiation

Thermoacoustic signals are generated over a large field of view by 900 ns TE10 pulses with 108 MHz carrier frequency. Test specimens selectively absorb the TE10 pulse energy producing rapid thermal expansions that generate ultrasonic pulses. 108 MHz irradiation provides excellent depth penetration in soft tissue, allowing blood and physiologic saline to generate strong signals. Thermoacoustic signal generation from a depth of several cm is well above our systems noise floor. Rotating the test specimen provides single-slice tomographic signal encoding. Filtered back-projection reconstruction yields images over a 6.4 cm field of view. Reconstructions of tissue mimicking prostate phantoms and fresh porcine kidney tissue are presented.

The Effect of Sample Holder Geometry on Electromagnetic Heating of Nanoparticle and NaCl Solutions at 13.56 MHz

Electromagnetic absorption and subsequent heating of nanoparticle solutions and simple NaCl ionic solutions is examined for biomedical applications in the radiofrequency range at 13.56 MHz. It is shown via both theory and experiment that for in vitro measurements the shape of the solution container plays a major role in absorption and heating.

Volumetric Thermoacoustic Imaging over Large Fields of View

The thermoacoustic (TA) contrast mechanism relies on rapid tissue heating and subsequent thermal expansion. TA computerized tomography (TCT) is therefore inverse source imaging. The TA contrast mechanism provides information complementary to that revealed by current diagnostic imaging techniques, but has been limited to just a few centimeters depth penetration. In this article, whole organ TCT is demonstrated on a large swine kidney. TA sinograms show that TA signal generated by high-power, very high frequency (VHF) electromagnetic pulses is detectable after travel through 6 cm of soft tissue. Reconstructed images provide resolution sufficient to track progression of calyces throughout the kidney. Because VHF electromagnetic energy can easily penetrate the abdomen of large adults, our results indicate that whole organ TA imaging is feasible in vivo, provided an ultrasound array can be placed near the region of interest. Pulses of 22 to 25 kW with carrier frequency 108 MHz and 900 ns pulse width were applied at a 100-Hz pulse repetition frequency to generate a 13-kV/m electric field and TA signal. Only 2 to 5 mJ was absorbed in the kidney per pulse, causing temperature and pressure jumps of only 5e-6°C and 4 Pa averaged throughout the 141-g specimen. TA pulses were detected by focused, single-element transducers (V306, Panametrics), amplified by 54 dB and averaged 64 times to reduce electronic noise. Data were measured over a cylindrical measurement aperture of radius 5 cm and length 6 cm, by rotating the specimen 1.8 degrees between tomographic views and translating 2 mm between slices. Reconstruction via filtered backprojection yields in-plane resolution better than 5 mm, but suffers significant blurring between planes. Both in-plane resolution and slice sensitivity profile could be improved by applying shorter irradiation pulsewidths and using less directional transducers. Both hardware changes would be recommended for a clinical prototype.

Thermoacoustic range verification using a clinical ultrasound array provides perfectly co-registered overlay of the Bragg peak onto an ultrasound image.

The potential of particle therapy due to focused dose deposition in the Bragg peak has not yet been fully realized due to inaccuracies in range verification. The purpose of this work was to correlate the Bragg peak location with target structure, by overlaying the location of the Bragg peak onto a standard ultrasound image. Pulsed delivery of 50 MeV protons was accomplished by a fast chopper installed between the ion source and the cyclotron inflector. The chopper limited the train of bunches so that 2 Gy were delivered in [Formula: see text]. The ion pulse generated thermoacoustic pulses that were detected by a cardiac ultrasound array, which also produced a grayscale ultrasound image. A filtered backprojection algorithm focused the received signal to the Bragg peak location with perfect co-registration to the ultrasound images. Data was collected in a room temperature water bath and gelatin phantom with a cavity designed to mimic the intestine, in which gas pockets can displace the Bragg peak. Phantom experiments performed with the cavity both empty and filled with olive oil confirmed that displacement of the Bragg peak due to anatomical change could be detected. Thermoacoustic range measurements in the waterbath agreed with Monte Carlo simulation within 1.2 mm. In the phantom, thermoacoustic range estimates and first-order range estimates from CT images agreed to within 1.5 mm.

Thermoacoustic contrast of prostate cancer due to heating by very high frequency irradiation.

Prostate cancer may be a good application for thermoacoustic imaging induced by very high frequency (VHF) radiation for several reasons. Mechanical properties of healthy and cancerous prostate tissue are well matched, so the assumption of constant sound speed is accurate. Signal production by VHF irradiation is proportional to ionic content, and ionic content of prostatic fluids produced by healthy tissue in the peripheral zone are approximately three times higher than in blood and plasma whereas cancer suppress ionic content of prostatic fluid. Signal strength is expected to decrease with extent of cancerous involvement. To test the utility of VHF-induced thermoacoustics to prostate cancer imaging we imaged fresh human prostate specimens ex vivo and compared to the gold standard, histology. Specimens were scanned immediately after radical prostatectomy performed as part of normal care.

Specific heat capacity of freshly excised prostate specimens

The specific heat capacity of tissue is a critical parameter for thermal therapies that act over a long period of time. It is also critical for thermoacoustic signal generation. We present ex vivo measurements of specific heat capacity performed by a dual-pin probe with tight temperature control of the specimen. One 30 mm × 1.28 mm probe heats steadily for 30 s, while another measurement probe measures temperatures 6 mm away from the center of the heater probe. Specific heat values ranging from 2.9 to 4 J cm(-3) °C(-1) were measured on 20 lobes from ten fresh prostate specimens with varying degrees of cancerous involvement as confirmed by histology.

Toward Quantitative Whole Organ Thermoacoustics With a Clinical Array Plus One Very Low-Frequency Channel Applied to Prostate Cancer Imaging

Thermoacoustics has the potential to provide quantitative images of intrinsic tissue properties, most notably electrical conductivity in Siemens/meter, much as shear wave elastography provides tissue stiffness in kilopascal. Although thermoacoustic imaging with optical excitation has been commercialized for small animals, it has not yet made the transition to clinic for whole organ imaging in humans. The purpose of this work was to develop and validate specifications for a clinical ultrasound array for quantitative whole organ thermoacoustic imaging. Imaging a large organ requires exciting thermoacoustic pulses throughout the volume and broadband detection of those pulses because tomographic image reconstruction preserves frequency content. Applying the half-wavelength limit to a 200-μm inclusion inside a 7.5-cm diameter organ requires measurement sensitivity to frequencies ranging from 4 MHz to 10 kHz, respectively. A dual-transducer system utilizing a P4-1 array connected to a Verasonics V1 system as well as a focused single-element transducer sensitive to lower frequencies was developed. Very high-frequency (VHF) irradiation generated thermoacoustic pulses throughout a 6 × 6 × 5 cm3 volume. In the VHF regime, electrical conductivity drives thermoacoustic signal production. Simultaneous acquisition of thermoacoustic pulses by both transducers enabled comparison of transducer performance. Data from the clinical array generated a stack of 96 images with a separation of 0.3 mm, whereas the single-element transducer imaged only in a single plane. In-plane resolution and quantitative accuracy were quantified at isocenter. The array provided volumetric imaging capability with superior resolution whereas the single-element transducer provided superior quantitative accuracy in axial images. Combining axial images from both transducers preserved resolution of the P4-1 array and improved image contrast. Neither transducer was sensitive to frequencies below 50 kHz, resulting in a dc offset and low-frequency shading over fields of view exceeding 15 mm. Fresh human prostates were imaged ex vivo and volumetric reconstructions reveal structures rarely seen in diagnostic images. In conclusion, quantitative whole-organ thermoacoustic tomography will be feasible by sparsely interspersing transducer elements sensitive to the low end of the ultrasonic range.