High-Resolution Photoacoustic Imaging of Ocular Tissues

Optical coherence tomography (OCT) and ultrasound (US) are methods widely used for diagnostic imaging of the eye. These techniques detect discontinuities in optical refractive index and acoustic impedance, respectively. Because these both relate to variations in tissue density or composition, OCT and US images share a qualitatively similar appearance. In photoacoustic imaging (PAI), short light pulses are directed at tissues, pressure is generated due to a rapid energy deposition in the tissue volume and thermoelastic expansion results in generation of broadband US. PAI thus depicts optical absorption, which is independent of the tissue characteristics imaged by OCT or US. Our aim was to demonstrate the application of PAI in ocular tissues and to do so with lateral resolution comparable to OCT. We developed two PAI assemblies, both of which used single-element US transducers and lasers sharing a common focus. The first assembly had optical and 35-MHz US axes offset by a 30° angle. The second assembly consisted of a 20-MHz ring transducer with a coaxial optics. The laser emitted 5-ns pulses at either 532 nm or 1064 nm, with spot sizes at the focus of 35 μm for the angled probe and 20 μm for the coaxial probe. We compared lateral resolution by scanning 12.5 μm diameter wire targets with pulse/echo US and PAI at each wavelength. We then imaged the anterior segment in whole ex vivo pig eyes and the choroid and ciliary body region in sectioned eyes. PAI data obtained at 1064 nm in the near infrared had higher penetration but reduced signal amplitude compared to that obtained using the 532 nm green wavelength. Images were obtained of the iris, choroid and ciliary processes. The zonules and anterior cornea and lens surfaces were seen at 532 nm. Because the laser spot size was significantly smaller than the US beamwidth at the focus, PAI images had superior resolution than those obtained using conventional US. (E-mail: rsilverman@rri-usa.org)     

Safety levels for exposure of cornea and lens to very high-frequency ultrasound.

OBJECTIVE: Very high-frequency (50-MHz) ultrasound is widely used for imaging the anterior segment of the eye. Our aim was to determine whether exposures to ultrasound at and above those used in diagnostic imaging systems might cause bioeffects in ocular tissues. METHODS: We characterized the output parameters of a polyvinylidene difluoride transducer using a needle hydrophone. We exposed sites on the cornea or lens of rabbits for up to 30 minutes at a 10-kHz pulse repetition frequency. Tissue obtained immediately or 24 hours after exposure was examined by light microscopy. A numeric model was implemented to calculate expected temperature elevations in the cornea and lens under experimental conditions. RESULTS: No tissue changes were observed directly or by slit lamp. Light microscopy showed no abnormalities attributable to ultrasound exposure. Simulations showed that even long-term exposures should produce temperature elevations of less than 1 degree C in both the cornea and lens. CONCLUSION: With the use of exposure parameters 4 to 5 orders of magnitude greater than encountered in a clinical situation, no tissue changes were observed. This is consistent with the small (0.2 degrees C) temperature rises computed in simulations. The lack of biological effects is attributable to the small dimensions of the focal zone, allowing rapid dissipation of heat, and the low total acoustic power produced by the transducer.     

Simultaneous real-time imaging of the ocular anterior segment including the ciliary muscle during accommodation

We demonstrated a novel approach of imaging the anterior segment including the ciliary muscle using combined and synchronized two spectral domain optical coherence tomography devices (SD-OCT). In one SD-OCT, a Complementary Metal-Oxide-Semiconductor Transistor (CMOS) camera and an alternating reference arm was used to image the anterior segment from the cornea to the lens. Another SD-OCT for imaging the ciliary muscle was equipped with a light source with a center wavelength of 1,310 nm and a bandwidth of 75 nm. Repeated measurements were performed under relaxed and 4.00 D accommodative stimulus states in six eyes from 6 subjects. We also imaged dynamic changes in the anterior segment in one eye during accommodation. The biometry of the anterior segment and the ciliary muscle was obtained. The combined system appeared to be capable to simultaneously real-time image the biometry of the anterior segment, including the ciliary muscle, in vivo during accommodation.OCIS codes: (170.4500) Optical coherence tomography, (170.3880) Medical and biological imaging, (170.4580) Optical diagnostics for medicine, (330.4460) Ophthalmic optics and devices, (330.7322) Visual optics, accommodation     

High frequency ultrasonic imaging of skin: experimental results

Experimental results are presented demonstrating the application of pulse echo ultrasound to imaging the skin. A laboratory prototype B-mode mechanical scanner was employed to obtain images of human skin, both in vitro and in vivo, using broadband pulsed ultrasound at 25 MHz. Images were formed by processing digitized A-mode waveforms and displaying the resulting two-dimensional cross sections using a digital imaging system. Images obtained by rectifying the A-modes are compared to those derived using a software-based cross-correlation technique. Scans of test targets demonstrate that an axial resolution of 100 m can be achieved at 25 MHz when the digital correlation method is employed. Lateral resolution is limited by the 0.25 mm half-power focal beamwidth of the transducer. Seventeen in vitro ultrasonic scans of human skin were compared to frozen section histology. Average skin depth was well correlated between the two techniques ( = 0.99, p less than 0.001). Application of cross-correlated processing to 25 MHz in vivo images produced good delineation of epidermis, papillary, and reticular dermis. Conversion to a 50 MHz transducer did not delineate skin layers as well as the 25 MHz transducer due to inherent difficulties with transducer reverberations.     

Fast,Low-Frequency Plane-Wave Imaging for Ultrasound Contrast Imaging

Plane-wave ultrasound contrast imaging offers a faster, less destructive means for imaging microbubbles compared with traditional ultrasound imaging. Even though many of the most acoustically responsive microbubbles have resonant frequencies in the lower-megahertz range, higher frequencies (>3 MHz) have typically been employed to achieve high spatial resolution. In this work we implement and optimize low-frequency (1.5-4 MHz) plane-wave pulse inversion imaging on a commercial, phased-array imaging transducer in vitro and illustrate its use in vivo by imaging a mouse xenograft model. We found that the 1.8-MHz contrast signal was about four times that acquired at 3.1 MHz on matched probes and nine times greater than echoes received on a higher-frequency probe. Low-frequency imaging was also much more resilient to motion. In vivo, we could identify sub-millimeter vasculature inside a xenograft tumor model and easily assess microbubble half-life. Our results indicate that low-frequency imaging can provide better signal-to-noise because it generates stronger non-linear responses. Combined with high-speed plane-wave imaging, this method could open the door to super-resolution imaging at depth, while high power pulses could be used for image-guided therapeutics.     

Preclinical Testing of Frequency-Tunable Capacitive Micromachined Ultrasonic Transducer Probe Prototypes

In intracardiac echocardiography (ICE) it may be beneficial to generate ultrasound images acquired at multiple frequencies, having the possibility of high penetration or high-resolution imaging in a single device. The objective of the presented work is to test two frequency-tunable probe prototypes in a preclinical setting: a rigid probe having a diameter of 11 mm and a new flexible and steerable 12-Fr ICE catheter. Both probes feature a forward-looking 32-element capacitive micromachined ultrasonic transducer array (aperture of 2 × 2 mm²) operated in collapse mode, which allows for frequency tuning in the 6-MHz–18-MHz range. The rigid probe prototype is tested ex vivo in a passive heart platform. Images of an aortic valve acquired in high-penetration (6 MHz), generic (12 MHz) and high-resolution (18 MHz) mode combine satisfying image quality and penetration depth between 2.5 cm and 10 cm. The ICE catheter prototype is tested in vivo using a porcine animal model. Images of an aortic valve are acquired in the 3 imaging modes with the ICE catheter placed in an ascending aorta at multiple depths. It was found that the combination of the forward-looking design and frequency-tuning capability allows visualizing intracardiac structures of various sizes at different distances relative to the catheter tip, providing both wide overviews and detailed close-ups.     

A 120-MHz Ultrasound Probe for Tissue Imaging

Ultrasound transducers with center frequency above 100 MHz are expected to be used for future diagnostic tissue characterization because of their high lateral resolution. We have fabricated a 120-MHz transducer that consists of a ZnO piezoelectric film on a sapphire substrate that has a concave acoustic lens. The lateral resolution was calculated as 13 μm. The insertion loss of the transducer, defined as the difference between the received voltage and the transmitted one, was −45 dB. The 6-dB bandwidth of the received signal was approximately 40 MHz. The transducer was mounted in a rod-shaped probe to ensure contact within vivotissue, because of the low penetration of ultrasound in the high frequency region. While the probe is rotated and moved along its axis mechanically, the transducer receives backscattered ultrasound from the surrounding tissue on a cylindrical plane that is kept a constant distance from the probe surface. The feasibility of this high-frequency tissue imaging probe has been demonstrated by obtaining preliminary images of anin vitrobovine kidney.     

A 100 MHz B-scan ultrasound backscatter microscope

The construction and operation of a 100 MHz B-mode ultrasound backscatter microscope are described. The powerful B-mode technique is extended into the domain of microscopy allowing the imaging of internal structure in living specimens on a microscopic scale. A frame rate of 5 frames per second is achieved which gives rapid feedback to the operator. Specially designed components of the scanner are described in detail, including the transducer, motion system and scan converter. An f/2 transducer is employed, leading to a scanner resolution of approximately 36 micron in both the lateral and axial directions. The benefits of such high resolution are demonstrated in preliminary images of multicellular spheroids and intact human ocular tissue.     

Laser Doppler holography of the anterior segment for blood flow imaging,eye tracking,and transparency assessment

Laser Doppler holography (LDH) is a full-field blood flow imaging technique able to reveal human retinal and choroidal blood flow with high temporal resolution. We here report on using LDH in the anterior segment of the eye without making changes to the instrument. Blood flow in the bulbar conjunctiva and episclera as well as in corneal neovascularization can be effectively imaged. We additionally demonstrate simultaneous holographic imaging of the anterior and posterior segments by simply adapting the numerical propagation distance to the plane of interest. We used this feature to track the movements of the retina and pupil with high temporal resolution. Finally, we show that the light backscattered by the retina can be used for retro-illumination of the anterior segment. Hence digital holography can reveal opacities caused by absorption or diffusion in the cornea and eye lens.     

Effect of Corneal Hydration on Ultrasound Velocity and Backscatter

The cornea's acoustic properties (speed-of-sound, backscatter, attenuation) are related to its state of hydration. Our aim was to determine these properties as a function of corneal hydration using high-frequency ultrasound. Bovine corneas were suspended in a Dexsol-equivalent corneal preservation medium at 33 °C and then immersed successively in 75%, 50% and 25% medium and distilled water. Using a 38-MHz focused ultrasound transducer, we measured speed-of-sound and corneal thickness (n = 8) and stromal backscatter (n = 6) after 45-min immersion in each medium. Corneal speed-of-sound was modeled as a function of corneal thickness. We found the mean speed-of-sound to be 1605.4 ± 2.9 m/s in normotensive medium. The maximum observed speed-of-sound was 1616 m/s. As we decreased medium tonicity, the cornea swelled and the speed-of-sound decreased, reaching 1563.0 ± 2.2 m/s in water. Average corneal thickness increased from 969 ± 93 μm in 100% medium to 1579 ± 104 μm in water. Going from 100% medium to water, stromal backscatter (midband-fit) increased from –60.0 ± 0.8 dBr to –52.5 ± 3.5 dBr, spectral slope increased from –0.119 ± 0.021 to –0.005 ± 0.030 dB/MHz and attenuation coefficient decreased from 0.927 ± 0.434 to 0.010 ± 0.581 dB/cm-MHz. The observed correlation between acoustic backscatter and attenuation with the speed-of-sound offers a potential means for more accurate determination of speed-of-sound and, hence, thickness in edematous corneas. (E-mail: ros2012@med.cornell.edu)     

Ultrasound measurement of the effect of temperature on microperfusion in the eye

Recent developments in ultrasound (US) technology have allowed the study of microperfusion in the anterior segment of the eye. Our aim was to determine the effect of the thermal environment on blood flow in the anterior segment. We measured blood flow in the major arterial circle of five rabbits. A 38-MHz US transducer was coupled to the eye with a normal saline water-bath with temperature controlled from 1 degrees C to 38 degrees C. The major arterial circle was localized and imaged using the swept-scan technique and M-mode data were then acquired for measurement of pulsatile flow. Peak systolic and mean velocity averaged 4.51 and 1.32 mm/s, respectively. Positive correlations were found between peak systolic (1.69%/ degrees C) and mean (1.76%/ degrees C) velocities and temperature. Vessel diameter (mean = 178 microm) did not show any significant change with temperature. High-resolution US flowmetry demonstrated decreasing flow rates in the iris with decreasing temperature.     

Cyclic changes in blood echogenicity under pulsatile flow are frequency dependent

Previous in vivo and in vitro studies have demonstrated that blood echogenicity varies under pulsatile flow, but such changes could not always be measured at physiological stroke rates. The apparent contradiction between these studies could be a result of the use of different ultrasound frequencies. Backscattered signals from porcine blood were measured in a pulsatile Couette flow apparatus. Cyclic changes in shear rate for stroke rates of 20 to 70 beats per minute (BPM) were applied to the Couette system, and different blood samples were analyzed (normal blood and blood with hyperaggregating erythrocytes promoted with dextran). To confirm that cyclic echogenicity variations were observable, spectral analysis was performed to verify if changes in echo-amplitude corresponded to the stroke rate applied to the flow. Echogenicity was measured with two single-element transducers at 10 and 35 MHz. At 35 MHz, cyclic variations in backscatter were observed from 20 to 70 BPM. However at 10 MHz, they were detected only at 20 BPM. For all cases except for hyperaggregating red blood cells (RBCs) at 20 BPM, the magnitude of the cyclic variations were higher at 35 MHz. We conclude that cyclic variations in RBC aggregation exist at physiological stroke rates, unlike what has been demonstrated in previous in-vitro studies at frequencies of 10 MHz. The increased sensitivity at 35 MHz to small changes in aggregate size might be the explanation for the better characterization of RBC aggregation at high stroke rates. Our results corroborate in-vivo observations of cyclic blood echogenicity variations in patients using a 30-MHz intravascular ultrasound catheter.     

Effect of ultrasound transducer frequency on the appearance of the fetal bowel.

We evaluated how ultrasound transducer frequency affected the appearance of the fetal bowel. One hundred women with singleton pregnancies, who were undergoing routine ultrasonographic examination, were assessed at a single institution. Patients with known fetal anomalies, abnormal biochemical screening results, or a history of cystic fibrosis were excluded. Images of the fetal abdomen were obtained in all patients using a single multi-Hertz transducer, with transducer frequencies set at 5 MHz and 8 MHz. Images were read separately by two radiologists, blinded to patient name and transducer frequency. Observers rated the presence or absence of echogenic bowel, defined as bowel with echogenicity greater than or equal to that of adjacent bone. Using the 8 MHz frequency, the radiologists interpreted 31% of the cases as having echogenic bowel, whereas using the 5 MHz frequency, the radiologists interpreted only 3% of the cases as having echogenic bowel (P<0.0001). A fetus was 10 times as likely to be given a diagnosis of echogenic bowel by both observers when the 8 MHz transducer was used than when the 5 MHz transducer was used by one observer (relative risk 10, 95% CI 3-11). Furthermore, using the 8 MHz frequency transducer, at least one of the radiologists interpreted echogenic bowel in 62% of the cases. We concluded that echogenic fetal bowel is a very common observation when imaging is performed with an 8 MHz transducer, and thus echogenic bowel diagnosed with an 8 MHz transducer is unlikely to reflect underlying abnormality. Identification of echogenic bowel with an 8 MHz transducer should not prompt further testing.     

Multiple-frequency ultrasonic imaging by transmitting pulsed waves of two frequencies

Purpose  The aim of this study was realization of a broadband measurement system that is capable of effectively carrying out a frequency compound method. In the present method, the secondary wave components of difference and sum frequencies are generated along with the higher harmonic components through the nonlinear interaction of two-frequency ultrasound. A multiple-frequency beam is generated together with the initially radiated frequency components. Methods  For the structure of a transducer capable of simultaneously radiating two sound waves with different frequencies, a coaxial arrangement of a circular-disc piezoelectric transducer and a ring piezoelectric transducer was designed. The radiating frequencies chosen were 2 and 8 MHz. In addition to the 4-MHz second harmonic sound of the 2-MHz primary sound, sounds of the 6-MHz difference frequency and the 10-MHz sum frequency can be generated. Results  By measuring the acoustic pressure distribution, the formation of a multiple-frequency beam was confirmed. The signal-to-noise ratio in an agar-gel phantom image was increased by 5–6 dB with application of the frequency compound method. The validity of the proposed method was demonstrated through the generation of a human finger image. Further, it was found that the influence of the Doppler effect was small enough that almost all the secondary waves were attributable to the nonlinear propagation of sounds. Conclusions  A multiple-frequency sound beam was realized by radiating a two-frequency sound. The effectiveness of the presented method was demonstrated through actual imaging.     

Transfontanelle photoacoustic imaging: ultrasound transducer selection analysis

Transfontanelle ultrasound imaging (TFUI) is the conventional approach for diagnosing brain injury in neonates. Despite being the first stage imaging modality, TFUI lacks accuracy in determining the injury at an early stage due to degraded sensitivity and specificity. Therefore, a modality like photoacoustic imaging that combines the advantages of both acoustic and optical imaging can overcome the existing TFUI limitations. Even though a variety of transducers have been used in TFUI, it is essential to identify the transducer specification that is optimal for transfontanelle imaging using the photoacoustic technique. In this study, we evaluated the performance of 6 commercially available ultrasound transducer arrays to identify the optimal characteristics for transfontanelle photoacoustic imaging. We focused on commercially available linear and phased array transducer probes with center frequencies ranging from 2.5MHz to 8.5MHz which covers the entire spectrum of the transducer arrays used for brain imaging. The probes were tested on both in vitro and ex vivo brain tissue, and their performance in terms of transducer resolution, size, penetration depth, sensitivity, signal to noise ratio, signal amplification and reconstructed image quality were evaluated. The analysis of selected transducers in these areas allowed us to determine the optimal transducer for transfontanelle imaging, based on vasculature depth and blood density in tissue using ex vivo sheep brain. The outcome of this evaluation identified the two most suitable ultrasound transducer probes for transfontanelle photoacoustic imaging.     

Acoustic techniques for assessing the Optison destruction threshold.

OBJECTIVE: The purpose of this study was to identify the pressure threshold for the destruction of Optison (octafluoropropane contrast agent; Amersham Health, Princeton, NJ) using a laboratory-assembled 3.5-MHz pulsed ultrasound system and a clinical diagnostic ultrasound scanner. METHODS: A 3.5-MHz focused transducer and a linear array with a center frequency of 6.9 MHz were positioned confocally and at 90 degrees to each other in a tank of deionized water. Suspensions of Optison (5-8x10(4) microbubbles/mL) were insonated with 2-cycle pulses from the 3.5-MHz transducer (peak rarefactional pressure, or Pr, from 0.0, or inactive, to 0.6 MPa) while being interrogated with fundamental B-mode imaging pulses (mechanical index, or MI,=0.04). Scattering received by the 3.5-MHz transducer or the linear array was quantified as mean backscattered intensity or mean digital intensity, respectively, and fit with exponential decay functions (Ae-kt+N, where A+N was the amplitude at time 0; N, background echogenicity; and k, decay constant). By analyzing the decay constants statistically, a pressure threshold for Optison destruction due to acoustically driven diffusion was identified. RESULTS: The decay constants determined from quantified 3.5-MHz radio frequency data and B-mode images were in good agreement. The peak rarefactional pressure threshold for Optison destruction due to acoustically driven diffusion at 3.5 MHz was 0.15 MPa (MI=0.08). Furthermore, the rate of Optison destruction increased with increasing 3.5-MHz exposure pressure output. CONCLUSIONS: Optison destruction was quantified with a laboratory-assembled 3.5-MHz ultrasound system and a clinical diagnostic ultrasound scanner. The pressure threshold for acoustically driven diffusion was identified, and 3 distinct mechanisms of ultrasound contrast agent destruction were observed with acoustic techniques.     

Developmental changes in integrated ultrasound backscatter from embryonic blood in vivo in mice at high US frequency

Mouse blood imaged using high-frequency ultrasound (US) is more echogenic in embryos than in adults. Studying changes in blood echogenicity in embryos may be of fundamental interest in studies on the genetic regulation of normal and abnormal blood development in mutant mice. Embryonic red blood cells (RBCs) are large and nucleated in midgestation but decrease in size and become enucleated as they mature. We therefore hypothesised that these structural alterations are responsible for variations in echogenicity of embryonic blood with gestational age and development. The objective of the current study was to quantify these structural changes in echogenicity (echo brightness) and apparent integrated backscatter (AIB) from embryonic blood at high US frequencies in vivo in mice. Results from anaesthetised pregnant mice studied using transcutaneous US showed that echogenicity of embryonic blood in the heart, aorta and umbilical cord and AIB within the heart chambers peaked at embryonic day (ED) 13.5 and then decreased progressively toward term. Between EDs 13.5 and 17.5 (near term), RBC mean cell volume decreased from 133 to 109 fL, haematocrit increased from 12 to 34%, and the percentage of nucleated RBCs decreased from 59 to 2%. Relative to younger ages, RBC nuclei at ED 13.5 were small and dense (pyknotic) which may have contributed to the peak in echogenicity and AIB at this age. To calculate the AIB, radiofrequency (RF) signals with centre frequencies of 28 MHz and 35 MHz were integrated over the 16- to 35-MHz and 21- to 42-MHz frequency range, respectively. At 28 MHz, mean apparent integrated backscatter of blood in the embryonic heart increased significantly from 0.0023 +/- 0.0004 Sr.cm(-1) (mean +/- SEM) at ED 12.5 to peak at 0.0037 +/- 0.0005 Sr.cm(-1) at ED 13.5. The mean AIB then decreased progressively with advancing gestation to 0.0002 +/- 0.0001 Sr.cm(-1) at ED 17.5. At 35 MHz, the mean AIB changed similarly with gestational age, except that values were lower than at 28 MHz at all ages. Higher attenuation of US at 35 MHz than at 28 MHz in tissue likely accounted for the lower AIB of blood insonified at 35 MHz. We speculate that developmental changes in red cell morphology are responsible for the observed changes in echogenicity and AIB of embryonic blood with gestational age in mice.     

Characterization of ultrasound propagation through ex-vivo human temporal bone

Adjuvant therapies that lower the thrombolytic dose or increase its efficacy would represent a significant breakthrough in the treatment of patients with ischemic stroke. The objective of this study was to perform intracranial measurements of the acoustic pressure field generated by 0.12, 1.03 and 2.00-MHz ultrasound transducers to identify optimal ultrasound parameters that would maximize penetration and minimize aberration of the beam. To achieve this goal, in vitro experiments were conducted on five human skull specimens. In a water-filled tank, two unfocused transducers (0.12 and 1.03 MHz) and one focused transducer (2.00 MHz) were consecutively placed near the right temporal bone of each skull. A hydrophone, mounted on a micropositioning system, was moved to an estimated location of the middle cerebral artery (MCA) origin, and measurements of the surrounding acoustic pressure field were performed. For each measurement, the distance from the position of maximum acoustic pressure to the estimated origin of the MCA inside the skulls was quantified. The -3 dB depth-of-field and beamwidth in the skull were also investigated as a function of the three frequencies. Results show that the transducer alignment relative to the skull is a significant determinant of the detailed behavior of the acoustic field inside the skull. For optimal penetration, insonation normal to the temporal bone was needed. The shape of the 0.12-MHz intracranial beam was more distorted than those at 1.03 and 2.00 MHz because of the large aperture and beamwidth. However, lower ultrasound pressure reduction was observed at 0.12 MHz (22.5%). At 1.03 and 2.00 MHz, two skulls had an insufficient temporal bone window and attenuated the beam severely (up to 96.6% pressure reduction). For all frequencies, constructive and destructive interference patterns were seen near the contralateral skull wall at various elevations. The 0.12-MHz ultrasound beam depth-of-field was affected the most when passing through the temporal bone and showed a decrease in size of more than 55% on average. The speed of sound in the temporal bone of each skull was estimated at 1.03 MHz and demonstrated a large range (1752.1 to 3285.3 m/s). Attenuation coefficients at 1.03 and 2.00 MHz were also derived for each of the five skull specimens. This work provides needed information on ultrasound beam shapes inside the human skull, which is a necessary first step for the development of an optimal transcranial ultrasound-enhanced thrombolysis device.     

Ultrasound properties of human prostate tissue during heating

Changes in the ultrasound (US) properties of tissue during heating affect the delivery of US thermal therapy and may provide a basis for US image monitoring of thermal therapy. The US attenuation coefficient and backscatter power of fresh human prostate tissue were measured as the tissue was heated. Samples of human prostate were obtained directly from autopsies and heated rapidly to final temperatures of 45 degrees C, 50 degrees C, 55 degrees C, 60 degrees C and 65 degrees C. A 5.0-MHz transducer was scanned in a raster pattern over the tissue and radiofrequency (RF) data were collected at 36 uncorrelated positions. Both attenuation and backscatter were measured over the frequency range 3.5 to 7.0 MHz at each min of a 30-min heating. Little change was observed in attenuation or backscatter at 55 degrees C or less. The attenuation coefficient and backscatter power increased by factors of 1.25 and 5, respectively, during the 60 degrees C heating. During the 65 degrees C heating, the same properties showed increases by factors of 2.7 and 9.     

Improved visualization of high-intensity focused ultrasound lesions

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 (approximately 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.