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Biomedical subjects

K Hynynen

Publications and source records attributed to K Hynynen.

At least 37 records · Page 2Linked to original sources
PubMed2001

The role of internal reflection in transskull phase distortion.

Phase distortion due to reflection in transcranial ultrasound propagation is investigated. Understanding of these phase-dependent properties is motivated by efforts to construct a reliable prediction model for noninvasive ultrasound therapy in the brain. The present study measures the phase of an ultrasound wave after propagation through an ex vivo human skull and considers the dependence of this phase on reflections between the transducer and the skull surface in addition to reflections within the skull. Experiments are performed using a human calvarium fragment placed between an underwater ultrasonic transducer and a polyvinylidene difluoride hydrophone. Data are presented indicating the ultrasound phase dependence as a function of burst length and the distance of the transducer element from the skull at a driving frequency of 0.5 MHz. Experimental results are compared with predictions obtained from a propagation model which considers transmission at the skull interfaces as well as multiple reflections within the skull. It is concluded that by using short ultrasound bursts a distance may be indicated that beyond which the contributions of transducer reflections on the phase of the propagating wave may be neglected. Additionally, a comparison of the measurements with simulated data supports the contention that for reasonably small incident angles, reflection within the skull causes minimal phase shift.

Brain↗
PubMed2001

Apoptosis in ultrasound-produced threshold lesions in the rabbit brain.

Focused ultrasound (US) surgery has been used to induce high temperature elevations in tissue to coagulate the proteins and kill the tissue. The introduction of noninvasive online temperature monitoring has made it possible to induce well-controlled thermal exposures. In this study, we used magnetic resonance imaging (MRI) thermometry to monitor thermal exposures near the threshold of tissue damage, and then investigated if apoptosis was induced. Rabbit brains were sonicated with an eight-sector phased array to create a large region of uniform temperature elevation at the end of a 30-s sonication. Histological examination demonstrated that apoptosis was induced in some cells. At 4 h after the sonications, the apoptotic cells constituted 9 +/- 7% of identifiable cells. By 48 h after the sonications, the number of apoptotic cells had increased up to 17 +/- 9%. The impact of this finding for therapy needs to be explored further.

Animals↗
PubMed2001

Thermal effects of focused ultrasound energy on bone tissue.

The effects of focused ultrasound (US) at therapeutic acoustic power levels were studied in vivo on the bone-muscle interface in rabbit thighs. The purpose of this study was to provide direction in establishing safety guidelines for treating tissue masses using focused US on or near bone. A positioning device was used to manipulate a focused US transducer (1.5 MHz) in a magnetic resonance imaging (MRI) scanner. This system was used to sonicate the femurs of 10 rabbits at acoustic power levels of 26, 39, 52 and 65 W for 10 s. The rabbits were euthanized either 4 h or 28 days after the sonications and the bone samples were harvested for histology examinations. In the femurs studied, acoustic power levels from 39 to 65 W resulted in soft tissue damage characterized grossly by coagulated tissue and bone damage depicted by yellow discoloration. Histologic examination of lesions from sonications from 39 to 65 W demonstrated that osteocyte damage and necrosis, characterized by pyknotic cells and empty lacunae, occurred within the ablation area extending through the bone. The follow-up MR images demonstrated an increase in the amount of damage in the femurs at 28 days posttreatment in comparison to images taken immediately after treatment. Focused US directed at the femur caused immediate significant thermal damage to bone in the form of osteocyte necrosis extending through the (approximately) 1 cm bone in this study. The results suggest that, when focused US energy is directed at or near bone-muscle interfaces, precautions should be taken to avoid thermal damage to the bone that can compromise its strength for extended periods.

Animals↗
PubMed2001

A focused ultrasound method for simultaneous diagnostic and therapeutic applications--a simulation study.

Similar to other therapeutic methods, ultrasound surgery requires an imaging modality to monitor the extent of tissue damage during treatment. In this paper, we have considered the method of ultrasound-stimulated acoustic emission (USAE) that uses two ultrasonic beams at high frequency (1.7 MHz) (same as that used for ablation) to locally excite the tissue by generating a low-frequency (1-50 kHz) radiation force. Recording of the tissue response at several locations yields an image. The amplitude of the tissue response depends on the mechanical and acoustic tissue properties, namely its stiffness and absorption. These two properties were initially hypothesized to have counteractive effects on the response amplitude, i.e., the amplitude should increase with absorption and decrease with stiffness. To check this hypothesis as well as the degree to which these properties influence the response, finite-element simulations of a uniform lesion formed inside a homogeneous medium were used. The results show that, as expected, the displacement amplitude decreased with increasing lesion stiffness at lower frequencies (except at resonance) while, contrary to our initial hypothesis, it increased with stiffness at relatively higher frequencies (>22 kHz). At resonance, a frequency upshift occurred with increasing stiffness but was found to be highly spatially variant and system dependent, i.e., not yielding a uniform lesion response when imaged. On the other hand, the absorption increase led to a uniform linear increase of the mechanical response amplitude of the lesion. Therefore, at higher frequencies, increase of the two parameters had a synergistic effect on the tissue response to the applied radiation force. This study showed that relatively higher frequencies constitute the optimal range in the use of USAE for coagulation monitoring. A preliminary experimental verification in vitro is also provided.

Animals↗
PubMed2001

Comparison of modelled and observed in vivo temperature elevations induced by focused ultrasound: implications for treatment planning.

Two numerical models for predicting the temperature elevations resulting from focused ultrasound heating of muscle tissue were tested against experimental data. Both models use the Rayleigh-Sommerfeld integral to calculate the pressure field from a source distribution. The first method assumes a source distribution derived from a uniformly radiating transducer whereas the second uses a source distribution obtained by numerically projecting pressure field measurements from an area near the focus backward toward the transducer surface. Both of these calculated ultrasound fields were used as heat sources in the bioheat equation to calculate the temperature elevation in vivo. Experimental results were obtained from in vivo rabbit experiments using eight-element sector-vortex transducers at 1.61 and 1.7 MHz and noninvasive temperature mapping with MRI. Results showed that the uniformly radiating transducer model over-predicted the peak temperature by a factor ranging from 1.4 to 2.8, depending on the operating mode. Simulations run using the back-projected sources were much closer to experimental values, ranging from 1.0 to 1.7 times the experimental results, again varying with mode. Thus, a significant improvement in the treatment planning can be obtained by using actual measured ultrasound field distributions in combination with backward projection.

Acoustics↗
PubMed2001

Temperature monitoring with line scan echo planar spectroscopic imaging.

UNLABELLED: A new magnetic resonance imaging method, line scan echo planar spectroscopic imaging (LSEPSI), is shown capable of providing rapid, internally referenced temperature monitoring from water and fat chemical shifts. METHODS: Orthogonal 90 degrees and 180 degrees slice selective RF pulses inclined by 45 degrees from the image plane solicit a spin echo from a tissue column. The echo is read by asymmetric sampling of 32 gradient echoes spaced 1.4-1.8 ms apart. Sixty-four adjacent columns are sequentially sampled in 4.2-6.4 s with 4,096 voxels sampled with voxel volumes of 0.08-0.13 cm3. Mixed mayonnaise/water phantoms were used to correlate LSEPSI-derived chemical shifts and thermocouple-based temperature measurements from 23 to 60 degrees C with a 1.5 T scanner. Measurement artifacts unrelated to temperature were investigated with the phantom, as was the feasibility of applying the sequence in human breast in vivo. RESULTS: The correlation between LSEPSI and thermocouple-based temperature measurements in the phantom was excellent (r2>0.99). Field drifts affecting the temperature measurements using the water peak alone were corrected by using the water/lipid peak difference. The sequence had an average temperature resolution of 1.4 degrees C in the phantom. The frequency difference measurement reduced the sensitivity to artifacts related to temperature. Both water and lipid peaks were detectable throughout many locations in the breast, suggesting the applicability of LSEPSI in this organ. DISCUSSION: T1-saturation losses occur in conventional and echo-planar based 2D CSI sequences using phase encoding methods with short TR periods. These losses are eliminated when individual columns are sampled in snapshot fashion with LSEPSI since the effective TR becomes the time between scans rather than excitations. T1 saturation can make small spectral peaks difficult to detect at high temperatures and generally lowers the signal-to-noise ratio of the spectra. The rapid acquisition and insensitivity to T1 saturation effects make LSEPSI an attractive technique for monitoring thermal therapies in breast using the internally referenced fat/water frequency separation.

Algorithms↗
PubMed2001

Simulations of the thermo-acoustic lens effect during focused ultrasound surgery.

Laboratory measurements of soft tissue properties show a dependence of background propagation properties on temperature. For typical focused ultrasound surgery (FUS) applications, only the slow variations in tissue background parameters need to be accounted for when computing the outcome of a FUS sonication. The cumulative effect of slowly varying sound speed has been referred to in the literature as a thermal lens, or a thermo-acoustic lens because of its beam-distorting properties. An algorithm to solve the coupled acoustic-thermal problem is described, and numerical results are presented to illustrate the effects of dynamic sound-speed profiles in layered tissues undergoing FUS. The results of simulations in liver with and without a fat layer indicate that the thermal-acoustic interaction results in more complex dynamics in FUS than a simple model will predict. Both the size and the position of the lesions predicted from the simulations are affected by the thermo-acoustic lens effect. However, the overall effect from short sonications at high power from sharply focused single element sources (F-no. from 0.8 to 1.3) around 1 MHz similar to those used in clinical setups is found to be small.

Acoustics↗
PubMed2001

Numerical analysis of ultrasonic transmission and absorption of oblique plane waves through the human skull.

Ultrasonic transmission and absorption of oblique plane waves through the human skull are analyzed numerically for frequencies ranging from 1/2 to 1 MHz. These frequencies are optimum for noninvasive ultrasound therapy of brain disorders where numerical predictions of skull transmission are used to set the phase and amplitude of source elements in the phased array focusing system. The idealized model of the skull is a three-layer solid with ivory outer and inner layers and a middle marrow layer. Each layer is modeled as a flat, homogeneous, isotropic, linear solid with effective complex wave speeds to account for focused energy losses due to material damping and scattering. The model is used to predict the amplitude and phase of the transmitted wave and volumetric absorption. Results are reported for three different skull thicknesses: 3 mm, 6 mm, and 9 mm. Thickness resonances are observed in the transmitted wave for 3 mm skulls at all frequencies and for the 6 mm skulls below 0.75 MHz. Otherwise, the transmission is dominated by the direct wave. Skull phase errors due to shear waves are shown to minimally degrade the power at the focus for angles of incidence up to 20 degrees from normal even for low material damping. The location of the peak volumetric absorption occurs either in the outer ivory or middle marrow layer and shown to vary due to wave interference.

Humans↗
PubMed2001

Noninvasive MR imaging-guided focal opening of the blood-brain barrier in rabbits.

PURPOSE: To determine if focused ultrasound beams can be used to locally open the blood-brain barrier without damage to surrounding brain tissue and if magnetic resonance (MR) imaging can be used to monitor this procedure. MATERIALS AND METHODS: The brains of 18 rabbits were sonicated (pulsed sonication) in four to six locations, with temporal peak acoustic power ranging from 0.2 to 11.5 W. Prior to each sonication, a bolus of ultrasonographic (US) contrast agent was injected into the ear vein of the rabbit. A series of fast or spoiled gradient-echo MR images were obtained during the sonications to monitor the temperature elevation and potential tissue changes. Contrast material-enhanced MR images obtained minutes after sonications and repeated 1-48 hours later were used to depict blood-brain barrier opening. Whole brain histologic evaluation was performed. RESULTS: Opening of the blood-brain barrier was confirmed with detection of MR imaging contrast agent at the targeted locations. The lowest power levels used produced blood-brain barrier opening without damage to the surrounding neurons. Contrast enhancement correlated with the focal signal intensity changes in the magnitude fast spoiled gradient-echo MR images. CONCLUSION: The blood-brain barrier can be consistently opened with focused ultrasound exposures in the presence of a US contrast agent. MR imaging signal intensity changes may be useful in the detection of blood-brain barrier opening during sonication.

Animals↗
PubMed2001

MR imaging-guided focused ultrasound surgery of fibroadenomas in the breast: a feasibility study.

PURPOSE: To test the feasibility of noninvasive magnetic resonance (MR) imaging-guided focused ultrasound surgery (FUS) of benign fibroadenomas in the breast. MATERIALS AND METHODS: Eleven fibroadenomas in nine patients under local anesthesia were treated with MR imaging-guided FUS. Based on a T2-weighted definition of target volumes, sequential sonications were delivered to treat the entire target. Temperature-sensitive phase-difference-based MR imaging was performed during each sonication to monitor focus localization and tissue temperature changes. After the procedure, T2-weighted and contrast material-enhanced T1-weighted MR imaging were performed to evaluate immediate and long-term effects. RESULTS: Thermal imaging sequences were improved over the treatment period, with 82% (279 of 342) of the hot spots visible in the last seven treatments. The MR imager was used to measure temperature elevation (12.8 degrees -49.9 degrees C) from these treatments. Eight of the 11 lesions treated demonstrated complete or partial lack of contrast material uptake on posttherapy T1-weighted images. Three lesions showed no marked decrease of contrast material uptake. This lack of effective treatment was most likely due to a lower acoustic power and/or patient movement that caused misregistration. No adverse effects were detected, except for one case of transient edema in the pectoralis muscle 2 days after therapy. CONCLUSION: MR imaging-guided FUS can be performed to noninvasively coagulate benign breast fibroadenomas.

Adult↗
PubMed2000

External beam radiotherapy and hyperthermia in the treatment of patients with locally advanced prostate carcinoma.

BACKGROUND: The current study was conducted to evaluate the combination of external beam radiation therapy and hyperthermia in the treatment of patients with locally advanced prostate carcinoma. METHODS: Twenty-six patients were treated on a Phase I/II protocol between June 1990 and April 1993. The median age of the patients was 69 years. Nine patients had well differentiated adenocarcinoma, ten patients had moderately differentiated adenocarcinoma, and six patients had poorly differentiated adenocarcinoma. All patients had American Urologic Society Stage C2-D1 adenocarcinoma. The median pretreatment prostate specific antigen (PSA) level was 29 ng/mL (range, 6-104 ng/mL). All patients received external beam radiation therapy using a four-field technique. The median radiation dose was 6,800 centigrays (cGy) given in 200-cGy fractions. Hyperthermia was administered concurrently with radiation therapy to temperatures of 42.5 degrees C for 30 minutes using a transrectal ultrasound applicator with 3 thermometry probes, given as either a single treatment (9 patients) or as two treatments (17 patients). Overall survival (OS) and biochemical no evidence of disease (bNED) status were calculated using Kaplan-Meier analysis. A consensus conference definition of PSA failure was used. The Cox proportional hazards model was used for multivariate analysis. The median follow-up for all patients was 71 months. RESULTS: The median time to PSA nadir was 15 months with a median PSA nadir value of 1.0 ng/mL. The median and 5-year OS was 88 months and 73%, respectively, and the median and 5-year bNED survival was 36 months and 35%, respectively. Multivariate analysis revealed only the pretreatment PSA level (P = 0.03) and the PSA nadir reached (P < 0.01) to be significant predictors of bNED survival. The duration of hyperthermia therapy showed a trend toward significance for OS (P = 0.06). CONCLUSIONS: The current Phase I/II protocol evaluating the combination of prostate hyperthermia and external beam radiation therapy for the treatment of patients with locally advanced prostate carcinoma suggests prostate hyperthermia to be feasible with no apparent significant increased toxicity, although there was no significant improvement in treatment outcome when compared with other studies reported in the literature evaluating external beam radiation therapy with or without androgen suppression. However, further investigation into the duration as well as the temperature of the hyperthermia with a greater number of patients is warranted.

Adenocarcinoma↗
PubMed2000

Temperature mapping using the water proton chemical shift: self-referenced method with echo-planar spectroscopic imaging.

An echo-planar spectroscopic imaging method of temperature mapping is proposed. This method is sufficiently faster than the so-called 3D magnetic resonance spectroscopic imaging (3D-MRSI) method and does not require image subtractions, unlike the conventional phase mapping method when an internal reference signal is detectable. The water proton chemical shift measured by using the tissue lipid as an internal reference clearly visualized the temperature change in a porcine liver sample in vitro. It was also demonstrated that the internally referenced echo-planar spectroscopic imaging method could markedly reduce a temperature error caused by a simple, translational motion between scans compared with the phase-mapping method.

Animals↗
PubMed2000

Temperature monitoring in fat with MRI.

The aim of the study was to test the hypothesis that fast spin echo T(1)-weighted images can be used to quantify the temperature in fat during thermal therapy in vivo. An MR compatible positioning device was used to manipulate focused ultrasound transducers in an MRI scanner. This system was used to sonicate fat tissue around the kidneys of 12 rabbits at various power levels for 10 to 20 sec. The scan parameters of T(1)-weighted fast spin echo (FSE) sequence were varied to optimize signal intensity characteristics while maintaining short scan times. An invasive optical probe was used to calibrate the temperature related signal intensity changes. For the T(1)-weighted FSE sequence, the signal intensity decreased with the temperature elevation at the rate of 0.97+/-0.02%/ degrees C. The single focused transducer produced a contrast-to-noise ratio more than 10 at power levels below the tissue damage threshold. The signal intensity was linearly dependent on the power, despite the measured temperatures being well above the coagulation threshold. This study demonstrates that T(1)-weighted FSE MRI sequences can be used to quantify the temperature elevation in fat in vivo during short focused ultrasound exposures. This can be very important for breast tumor surgery, fat ablation, and for treating deep seated tumors through superficial fat layers. Magn Reson Med 43:901-904, 2000.

Adipose Tissue↗
PubMed2000

Simultaneous measurements of temperature and pH in vivo using NMR in conjunction with TmDOTP5-.

NMR techniques for temperature and pH measurements have attracted increasing interest in recent years, motivated in part by the growing importance of medical hyperthermia for the treatment of cancer. The chemical shifts of thulium 1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetrakis(methylene phosphonate) (TmDOTP5-) have been studied as a function of temperature and pH. The results demonstrate that TmDOTP5- resonance shifts are highly sensitive to temperature (approximately 1.0 ppm/degrees C) and pH (approximately 3.2 ppm/pH unit) at clinically relevant field strengths. A new method is presented which utilizes two magnetically non-equivalent protons in TmDOTP5- for simultaneous NMR measurements of both temperature and pH. The difference in the chemical shift values of pairs of 1H resonances provides a temperature sensitivity of about 1.6 ppm/ degrees C. The technique is demonstrated in live rats undergoing ultrasound-induced hyperthermia therapy.

Animals↗
PubMed2000

MRI detection of the thermal effects of focused ultrasound on the brain.

This study tested the hypothesis that MRI thermometry can be correlated with the different degrees of tissue damage observed after focused ultrasound (US) exposure of brain. The brains of 6 rabbits were sonicated to calibrate the MRI proton resonant shift with temperature. In addition, 13 rabbits were sonicated at acoustic powers ranging from 3.5 to 17.5 W. The experiments were performed in a 1.5-T MRI scanner with the temperature-sensitive phase imaging used during the sonications of 4-5 different locations in each rabbit. MR images were obtained 2 h and 2 days after the sonications, depending on when the animals were sacrificed. Whole brain histologic evaluation was performed by sectioning the brain and performing a microscopic investigation. The MRI-derived temperature elevation was found to correlate well with the degree of tissue damage. In addition to the common histology findings, apoptotic cells were observed in the lesions. The T1-weighted contrast enhanced and T2-weighted scans both detected the brain damage. The applied acoustic power did not correlate well with the degree of damage. As a conclusion, the results showed that the measurement of temperature elevations by MRI during sonications can improve the accuracy and safety of clinical US brain surgery.

Animals↗
PubMed2000

A hemisphere array for non-invasive ultrasound brain therapy and surgery.

Ultrasound phased arrays may offer a method for non-invasive deep brain surgery through the skull. In this study a hemispherical phased array system is developed to test the feasibility of trans-skull surgery. The hemispherical shape is incorporated to maximize the penetration area on the skull surface, thus minimizing unwanted heating. Simulations of a 15 cm radius hemisphere divided into 11, 64, 228 and 512 elements are presented. It is determined that 64 elements are sufficient for correcting scattering and reflection caused by trans-skull propagation. An optimal operating frequency near 0.7 MHz is chosen for the array from numerical and experimental thermal gain measurements comparing the power between the transducer focus and the skull surface. A 0.665 MHz air-backed PZT array is constructed and evaluated. The array is used to focus ultrasound through an ex vivo human skull and the resulting fields are measured before and after phase correction of the transducer elements. Finally, to demonstrate the feasibility of trans-skull therapy, thermally induced lesions are produced through a human skull in fresh tissue placed at the ultrasound focus inside the skull.

Algorithms↗
PubMed2000

Investigation of a large-area phased array for focused ultrasound surgery through the skull.

Non-invasive treatment of brain disorders using ultrasound would require a transducer array that can propagate ultrasound through the skull and still produce sufficient acoustic pressure at a specific location within the brain. Additionally, the array must not cause excessive heating near the skull or in other regions of the brain. A hemisphere-shaped transducer is proposed which disperses the ultrasound over a large region of the skull. The large surface area covered allows maximum ultrasound gain while minimizing undesired heating. To test the feasibility of the transducer two virtual arrays are simulated by superposition of multiple measurements from an 11-element and a 40-element spherically concave test array. Each array is focused through an ex vivo human skull at four separate locations around the skull surface. The resultant ultrasound field is calculated by combining measurements taken with a polyvinylidene difluoride needle hydrophone providing the fields from a 44-element and a 160-element virtual array covering 88% and 33% of a hemisphere respectively. Measurements are repeated after the phase of each array element is adjusted to maximize the constructive interference at the transducer's geometric focus. An investigation of mechanical and electronic beam steering through the skull is also performed with the 160-element virtual array, phasing it such that the focus of the transducer is located 14 mm from the geometric centre. Results indicate the feasibility of focusing and beam steering through the skull using an array spread over a large surface area. Further, it is demonstrated that beam steering through the skull is plausible.

Bone and Bones↗