Biomedical subjects

K Hynynen

Publications and source records attributed to K Hynynen.

At least 19 recordsLinked to original sources

PubMed2006

Local frequency dependence in transcranial ultrasound transmission.

The development of large-aperture multiple-source transducer arrays for ultrasound transmission through the human skull has demonstrated the possibility of controlled and substantial acoustic energy delivery into the brain parenchyma without the necessitation of a craniotomy. The individual control of acoustic parameters from each ultrasound source allows for the correction of distortions arising from transmission through the skull bone and also opens up the possibility for electronic steering of the acoustic focus within the brain. In addition, the capability to adjust the frequency of insonation at different locations on the skull can have an effect on ultrasound transmission. To determine the efficacy and applicability of a multiple-frequency approach with such a device, this study examined the frequency dependence of ultrasound transmission in the range of 0.6-1.4 MHz through a series of 17 points on four ex vivo human skulls. Effects beyond those that are characteristic of frequency-dependent attenuation were examined. Using broadband pulses, it was shown that the reflected spectra from the skull revealed information regarding ultrasound transmission at specific frequencies. A multiple-frequency insonation with optimized frequencies over the entirety of five skull specimens was found to yield on average a temporally brief 230% increase in the transmitted intensity with an 88% decrease in time-averaged intensity transmission within the focal volume. This finding demonstrates a potential applicability of a multiple-frequency approach in transcranial ultrasound transmission.

Cadaver↗

PubMed2006

Targeted disruption of the blood-brain barrier with focused ultrasound: association with cavitation activity.

Acoustic emission was monitored during focused ultrasound exposures in conjunction with an ultrasound contrast agent (Optison) in order to determine if cavitation activity is associated with the induction of blood-brain barrier disruption (BBBD). Thirty-four locations were sonicated (frequency: 260 kHz) at targets 10 mm deep in rabbit brain (N = 9). The sonications were applied at peak pressure amplitudes ranging from 0.11 to 0.57 MPa (burst length: 10 ms; repetition frequency of 1 Hz; duration: 20 s). Acoustic emission was recorded with a focused passive cavitation detector. This emission was recorded at each location during sonications with and without Optison. Detectable wideband acoustic emission was observed only at 0.40 and 0.57 MPa. BBBD was observed in contrast MRI after sonication at 0.29-0.57 MPa. The appearance of small regions of extravasated erythrocytes appeared to be associated with this wideband emission signal. The results thus suggest that BBBD resulting from focused ultrasound pulses in the presence of Optison can occur without indicators for inertial cavitation in vivo, wideband emission and extravasation. If inertial cavitation is not responsible for the BBBD, other ultrasound/microbubble interactions are likely the source. A significant increase in the emission signal due to Optison at the second and third harmonics of the ultrasound driving frequency was found to correlate with BBBD and might be useful as an online method to indicate when the disruption occurs.

Albumins↗

PubMed2006

Longitudinal and shear mode ultrasound propagation in human skull bone.

Recent studies have attempted to dispel the idea of the longitudinal mode being the only significant mode of ultrasound energy transport through the skull bone. The inclusion of shear waves in propagation models has been largely ignored because of an assumption that shear mode conversions from the skull interfaces to the surrounding media rendered the resulting acoustic field insignificant in amplitude and overly distorted. Experimental investigations with isotropic phantom materials and ex vivo human skulls demonstrated that, in certain cases, a shear mode propagation scenario not only can be less distorted, but at times allowed for a substantial (as much as 36% of the longitudinal pressure amplitude) transmission of energy. The phase speed of 1.0-MHz shear mode propagation through ex vivo human skull specimens has been measured to be nearly half of that of the longitudinal mode (shear sound speed = 1500 +/- 140 m/s, longitudinal sound speed = 2820 +/- 40 m/s), demonstrating that a closer match in impedance can be achieved between the skull and surrounding soft tissues with shear mode transmission. By comparing propagation model results with measurements of transcranial ultrasound transmission obtained by a radiation force method, the attenuation coefficient for the longitudinal mode of propagation was determined to between 14 Np/m and 70 Np/m for the frequency range studied, while the same for shear waves was found to be between 94 Np/m and 213 Np/m. This study was performed within the frequency range of 0.2 to 0.9 MHz.

Acoustics↗

PubMed2005

Resonance frequency of microbubbles in small blood vessels: a numerical study.

Microbubbles are currently used as ultrasound contrast agents. Their potential therapeutic applications are also under investigation. This work is designed to provide some insight into the mechanisms of energy absorption and deposition by a preformed gas bubble in the microvasculature to optimize its efficacy. In the linear regime, the most favourable condition for the transfer of energy from an ultrasonic field to a gas bubble occurs when the centre frequency of the ultrasonic field equals the resonance frequency of the bubble. The resonance frequency of gas microbubbles has been investigated up to now mainly in unbounded liquids; however when bubbles are confined in small regions, their resonance frequency is strongly affected by the surrounding boundaries. A parametric study on how the resonance frequency of microbubbles in blood vessels is affected by the bubble radius, vessel radius and the bubble position in the vessel is presented. The resonance frequency decreases below its free value with decreasing vessel radius for vessels smaller than 200-300 microm depending on the bubble size. This model suggests the possibility of using ultrasound in a range of frequencies that are, in general, lower than the ones used now for therapeutic and diagnostic applications of ultrasound (a few MHz). When microbubbles oscillate at their resonance frequency they absorb and therefore emit more energy. This energy may allow specific blood vessels to be targeted for both diagnostic and therapeutic applications of ultrasound.

Blood Vessels↗

PubMed2005

Theoretical and experimental validation of a dual-frequency excitation method for spatial control of cavitation.

Inertial cavitation has been implicated as the primary mechanism for a host of emerging applications. In all these applications, the main concern is to induce cavitation in perfectly controlled locations in the field; this means specifically to be able to achieve the cavitation threshold at the geometrical focus of the transducer without stimulating its near field. In this study, we develop dual-frequency methods to preferentially lower the cavitation threshold at the focus relative to the rest of the field. Two families of dual-frequency driving waveforms are evaluated in a bubble model incorporating rectified diffusion. Results are then verified by experiment. Finally, the performance of the rest of acoustic field in suppressing cavitation when cavitation is induced at the focus is investigated theoretically and checked experimentally. This study shows that dual-frequency phased arrays could be used to precisely control cavitation. The cavitation threshold is proved to be 1.2 times higher in the near field than at the focus. The concept of cavitation field is introduced and complements cavitation studies concentrating on the focal behaviour only.

Computer Simulation↗

PubMed2005

Ultrasound phase-contrast transmission imaging of localized thermal variation and the identification of fat/tissue boundaries.

We present a new ultrasound technique for registering localized temperature changes in soft tissues. Conversely, small temperature changes may be induced in order to image tissue layers. The concept is motivated by the search for a compact, low cost method for guiding noninvasive thermal therapies; however its utility may extend to a wide range of imaging problems such as tumour imaging in the breast. This method combines ultrasound transmission imaging, planar projection techniques and phase-contrast theory. After outlining the theoretical foundation of the technique, its feasibility is tested by simulating localized heating within homogeneous tissue layers. Success of this imaging method is evaluated as a function of the ultrasound-imaging wavelength for a Gaussian-shaped heated region over the frequency range from 0.1 to 2 MHz. Furthermore we simulate two-dimensional image reconstruction from a receiving array. We conclude that thermal phase-contrast imaging in tissues is plausible for detecting the treatment spot in thermal therapies while operating at frequencies below 1 MHz. Additionally, it may also be possible to use the method for noninvasive thermometry. However, thermometry would require operation at higher frequencies at the tradeoff of increased attenuation and higher sensitivity to scattering, which needs to be further explored.

Body Temperature↗

PubMed2005

Superresolution ultrasound imaging using back-projected reconstruction.

An ultrasound technique for imaging objects significantly smaller than the source wavelength is investigated. Signals from a focused beam are recorded over an image plane in the acoustic farfield and backprojected in the wave-vector domain to the focal plane. A superresolution image recovery method is then used to analyze the Fourier spatial frequency spectrum of the signal in an attempt to deduce the location and size of objects in this plane. The physical foundation for the method is rooted in the fact that high spatial frequencies introduced by the object in fact affect the lower (nonevanescent) spatial frequencies of the overall signal. The technique achieves this by using a priori measurements of the ultrasound focus in water, which gives full spectral information about the image source. A guess is then made regarding the size and location of the object that distorted the field, and this is convolved with the a priori measurement, thus creating a candidate image. A large number of candidates are generated and the one whose spectrum best matches the uncorrected image is accepted. The method is demonstrated using 0.34- and 0.60-mm wires with a focused 1.05-MHz ultrasound signal and then a human hair (approximately 0.03 mm) with a 4.7-MHz signal.

Acoustics↗

PubMed2004

Estimating localized oscillatory tissue motion for assessment of the underlying mechanical modulus.

The technique of harmonic motion imaging (HMI) uses the localized stimulus of the oscillatory ultrasonic radiation force as produced by two overlapping beams of distinct frequencies, and estimates the resulting harmonic displacement in the tissue in order to assess its underlying mechanical properties. In this paper, we studied the relationship between measured displacement and stiffness in gels and tissues in vitro. Two focused ultrasound transducers with a 100 mm focal length were used at frequencies of 3.7500 MHz and either 3.7502 (or 3.7508 MHz), respectively, in order to produce an oscillatory motion at 200 Hz in the gel or tissue. A 1.1 MHz diagnostic transducer (Imasonics, Inc.) was also focused at 100 mm and acquired 5 ms RF signals (pulse repetition frequency (PRF)=3.5 kHz) at 100 MHz sampling frequency during radiation force application. First, three 50x50 mm(2) acrylamide gels were prepared at concentrations of 4%, 8% and 16%. The resulting displacement was estimated using crosscorrelation techniques between successively acquired RF signals with a 2 mm window and 80% window overlap at 1260 W/cm(2). A normal 1-D indentation instrument (TeMPeST) applied oscillatory loads at 0.1-200 Hz with a 5 mm-diameter flat indenter. Then, 12 displacement measurements in 6 porcine muscle specimens (two measurements/case, as above) were made in vitro, before and after ablation which was performed for 10 s at 1260 W/cm(2). In all gel cases, the harmonic displacement was found to linearly increase with intensity and exponentially decrease with gel concentration. The TeMPeST measurements showed that the elastic moduli for the 4%, 8% and 16% gels equaled 3.93+/-0.06, 17.1+/-0.2 and 75+/-2 kPa, respectively, demonstrating that the HMI displacement estimate depends directly on the gel stiffness. Finally, in the tissues samples, the mean displacement amplitude showed a twofold decrease between non-ablated and ablated tissue, demonstrating a correspondence between the HMI response and an increase in stiffness measured with the TeMPeST instrument.

Animals↗

PubMed2004

MRI guided and monitored focused ultrasound thermal ablation methods: a review of progress.

This paper reviews the current status in using magnetic resonance imaging (MRI) to guide and monitor thermal coagulation of tumours using focused ultrasound. The patient treatment procedure with a second generation phased array system will be described. Several clinical trials have found that patient treatments are feasible and that MRI thermometry allows noninvasive monitoring of clinical treatments. Overall, this emerging modality holds significant potential for non-invasive tumour treatment of both benign and malignant tumours.

Humans↗

PubMed2004

Enhanced ultrasound transmission through the human skull using shear mode conversion.

A new transskull propagation technique, which deliberately induces a shear mode in the skull bone, is investigated. Incident waves beyond Snell's critical angle experience a mode conversion from an incident longitudinal wave into a shear wave in the bone layers and then back to a longitudinal wave in the brain. The skull's shear speed provides a better impedance match, less refraction, and less phase alteration than its longitudinal counterpart. Therefore, the idea of utilizing a shear wave for focusing ultrasound in the brain is examined. Demonstrations of the phenomena, and numerical predictions are first studied with plastic phantoms and then using an ex vivo human skull. It is shown that at a frequency of 0.74 MHz the transskull shear method produces an amplitude on the order of--and sometimes higher than--longitudinal propagation. Furthermore, since the shear wave experiences a reduced overall phase shift, this indicates that it is plausible for an existing noninvasive transskull focusing method [Clement, Phys. Med. Biol. 47(8), 1219-1236 (2002)] to be simplified and extended to a larger region in the brain.

Absorption↗

PubMed2004

Forced linear oscillations of microbubbles in blood capillaries.

A theoretical investigation of the forced linear oscillations of a gas microbubble in a blood capillary, whose radius is comparable in size to the bubble radius is presented. The natural frequency of oscillation, the thermal and viscous damping coefficients, the amplitude resonance, the energy resonance, as well as the average energy absorbed by the system, bubble plus vessel, have been computed for different kinds of gas microbubbles, containing air, octafluropropane, and perflurobutane as a function of the bubble radius and applied frequency. It has been found that the bubble behavior is isothermal at low frequencies and for small bubbles and between isothermal and adiabatic for larger bubbles and higher frequencies, with the viscous damping dominating over the thermal damping. Furthermore, the width of the energy resonance is strongly dependent on the bubble size and the natural frequency of oscillation is affected by the presence of the vessel wall and position of the bubble in the vessel. Therefore, the presence of the blood vessel affects the way in which the bubble absorbs energy from the ultrasonic field. The motivation of this study lies in the possibility of using gas microbubbles as an aid to therapeutic focused ultrasound treatments.

Biomechanical Phenomena↗

PubMed2003

MRI-guided gas bubble enhanced ultrasound heating in in vivo rabbit thigh.

In this study, we propose a focused ultrasound surgery protocol that induces and then uses gas bubbles at the focus to enhance the ultrasound absorption and ultimately create larger lesions in vivo. MRI and ultrasound visualization and monitoring methods for this heating method are also investigated. Larger lesions created with a carefully monitored single ultrasound exposure could greatly improve the speed of tumour coagulation with focused ultrasound. All experiments were performed under MRI (clinical, 1.5 T) guidance with one of two eight-sector, spherically curved piezoelectric transducers. The transducer, either a 1.1 or 1.7 MHz array, was driven by a multi-channel RF driving system. The transducer was mounted in an MRI-compatible manual positioning system and the rabbit was situated on top of the system. An ultrasound detector ring was fixed with the therapy transducer to monitor gas bubble activity during treatment. Focused ultrasound surgery exposures were delivered to the thighs of seven New Zealand while rabbits. The experimental, gas-bubble-enhanced heating exposures consisted of a high amplitude 300 acoustic watt, half second pulse followed by a 7 W, 14 W or 21 W continuous wave exposure for 19.5 s. The respective control sonications were 20 s exposures of 14 W, 21 W and 28 W. During the exposures, MR thermometry was obtained from the temperature dependency of the proton resonance frequency shift. MRT2-enhanced imaging was used to evaluate the resulting lesions. Specific metrics were used to evaluate the differences between the gas-bubble-enhanced exposures and their respective control sonications: temperatures with respect to time and space, lesion size and shape, and their agreement with thermal dose predictions. The bubble-enhanced exposures showed a faster temperature rise within the first 4 s and higher overall temperatures than the sonications without bubble formation. The spatial temperature maps and the thermal dose maps derived from the MRI thermometry closely correlated with the resulting lesion as examined by T2-weighted imaging. The lesions created with the gas-bubble-enhanced heating exposures were 2-3 times larger by volume, consistently more spherical in shape and closer to the transducer than the control exposures. The study demonstrates that gas bubbles can reliably be used to create significantly larger lesions in vivo. MRI thermometry techniques were successfully used to monitor the thermal effects mediated by the bubble-enhanced exposures.

Adipose Tissue↗

PubMed2003

MRI feedback temperature control for focused ultrasound surgery.

A temperature feedback controller routine using a physical model for temperature evolution was developed for use with focused ultrasound surgery. The algorithm for the controller was a multi-input, single-output linear quadratic regulator (LQR) derived from Pennes' bioheat transfer equation. The controller was tested with simulated temperature data that had the same characteristics as those obtained with magnetic resonance imaging (MRI). The output of the controller was the appropriate power level to be used by the transducer. Tissue parameters estimated prior to the simulated treatments were used to determine the controller parameters. The controller performance was simulated in three dimensions with varying system parameters, and sufficient temperature tracking was achieved. The worst-case overshoot was 7 degrees C and the steady-state error was 5 degrees C. The simulated behaviour of the controller suggests satisfactory performance and that the controller may be useful in controlling the power output during MRI-monitored ultrasound surgery.

Computer Simulation↗

PubMed2003

Non-invasive opening of BBB by focused ultrasound.

Blood brain barrier (BBB) is a major barrier for delivering therapeutic agents in the brain. In this study we investigated the feasibility of open the BBB by using focused ultrasound. Rabbit brains were exposed to pulsed focused ultrasound while injecting ultrasound contrast agent containg microbubbles intravenously. The BBB opening was measured after the sonications by injecting MRI contrast agent i.v. and evaluating the local enhancement in the brain. Low ultrasound powers and pressure amplitudes were found to cause focal enhancement. Before sacrificing the animals trypan blue was also injected i.v.. After the sacrifice of the animals blue spots were found in the brain in the sonicated locations. This method may have potential for targeted delivery of macromolecules in the brain.

Animals↗

PubMed2003

Preliminary results using ultrasound transmission for image-guided thermal therapy.

The feasibility of using an acoustic camera as a real-time imaging device for thermal surgery was investigated. The study compares camera images of tissue samples taken before, during and after a volume of tissue was thermally coagulated using focused ultrasound (US). This apparatus has analogous acoustic counterparts to an optical charge couple device (CCD) camera. The setup was operated in transmission mode, with a tissue sample placed between the camera and a 10-MHz illuminating transducer. A high-intensity continuous-wave US signal from a therapeutic transducer was focused inside the sample tissue. A reversible, time-dependent variation in image intensity was observed in the region of the therapeutic sonications in all tissues tested: bovine fat and porcine and rabbit livers. Correlations between image intensities and temperatures were shown; rabbit liver resulted in a correlation coefficient (R(2)) of 0.6694 and bovine fat resulted in an R(2) of 0.9455. When temperatures high enough to coagulate tissue were reached, permanent changes in the images were observed. Lesion locations and dimensions from the images were found to be comparable to the sectioned tissue samples. An R(2) of 0.919 resulted when lesion size detected from the camera was compared to the actual lesion size. Preliminary results may indicate that the camera has an application for monitoring thermal surgery.

Animals↗

PubMed2003

Focused ultrasound (HIFU) induces localized enhancement of reporter gene expression in rabbit carotid artery.

The development of accurate, safe, and efficient gene delivery remains a major challenge towards the realization of gene therapeutic prevention and treatment of cardiovascular diseases. In this study, we investigated the ability of high-intensity focused ultrasound (HIFU), a form of mechanical wave transmission, to act as a noninvasive tool for the enhancement of in vivo gene transfer into rabbit carotid arteries. Segments of the common carotid arteries of New Zealand white rabbits were isolated and infused with plasmid DNA encoding the reporter beta-galactosidase either with or without the addition of ultrasound contrast agent consisting of small (approximately 2-5 microm) gas-filled human albumin microspheres to augment cavitation. Infused arteries were exposed to pulsed ultrasound for 1 min (frequency 0.85 MHz, burst length 50 ms, repetition frequency 1 Hz, duration 60 s, peak pressure amplitude of 15 MPa). At 6.3 MPa, HIFU enhanced gene expression eight-fold, and 17.5-fold in the presence of contrast. We found increasing amounts of beta-galactosidase expression in the carotid vessel with increasing pressure amplitude. This dose-response relation was present with and without contrast. Without contrast, no vessel damage was detected up to 15 MPa, while the addition of contrast induced side effects above a threshold of 6.3 MPa peak pressure. The entire procedure was feasible and safe for the animals, and the results suggest that HIFU has the potential to assist in the noninvasive spatial regulation of gene transfer into the vascular system.

Animals↗

PubMed2002

A non-invasive method for focusing ultrasound through the human skull.

A technique for focusing ultrasound through the human skull is described and verified. The approach is based on a layered wavevector-frequency domain model, which propagates ultrasound from a hemisphere-shaped transducer through the skull using input from CT scans of the head. The algorithm calculates the driving phase of each transducer element in order to maximize the signal at the intended focus. This approach is tested on ten ex vivo human skulls using a 0.74 MHz, 320-element array. A stereotaxic reference frame is affixed to the skulls in order to provide accurate registration between the CT images and the transducer. The focal quality is assessed with a hydrophone placed inside the skull. In each trial the phase correction algorithm successfully restored the focus inside the skull at a location within 1 mm from the intended focal point. The results demonstrate the feasibility of using the method for completely non-invasive ultrasound brain surgery and therapy.

Humans↗

PubMed2001

MRI monitoring of the thermal ablation of tissue: effects of long exposure times.

MRI-derived thermometry based on the temperature-dependence of the proton resonant frequency (PRF) is extremely sensitive to changes in tissue unrelated to temperature changes, including tissue swelling. This study investigated the maximum amount of time that this phase-subtraction-based method can be used to accurately monitor temperature changes in vivo. Long-duration focused ultrasound sonications were delivered in rabbit thigh muscle with a phased-array transducer, and the time that tissue swelling began was monitored. Tissue swelling began to occur at about one minute. The temperature correlated well with an implanted thermocouple up to this time. After this time, severe artifacts in the phase-difference maps were observed. The thermal dose model predicted the extent of tissue damage well for subsequent one minute sonications. These results will have implications for MRI guidance of thermal therapies with long exposure times.

Animals↗