Effect of tissue perfusion on temperature elevation.
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Animals↗
Biomedical subjects
K Hynynen
Publications and source records attributed to K Hynynen.
Induction of hyperthermia using an intracavitary multielement ultrasonic applicator.
In this paper, the possibility of inducing controlled hyperthermia in rectal or vaginal wall tumors using an intracavitary ultrasonic applicator was investigated. A computer model that took into account the thermal and ultrasonic properties of tissues and surface cooling was used to optimize the transducer parameters to obtain desirable temperature distributions for different perfusion situations in the tumor. Also, an applicator that consisted of a cylindrical array of five independently controllable ultrasonic transducers was developed. This array was then tested in degassed water to determine the functional characteristics. This same applicator, modified to include water cooling of the tissue surface, was tested in vivo in dogs. The temperature distributions were found to be promising and with modifications this approach will be used in clinical treatments of suitable tumors.
Animals↗
Demonstration of enhanced temperature elevation due to nonlinear propagation of focussed ultrasound in dog's thigh in vivo.
The results of an experimental study quantifying the temperature elevation gains produced by nonlinear propagation of focussed ultrasound fields in dogs' thighs in vivo are presented. Also, the intensity dependence of power absorption from a focussed ultrasound field was studied. The absorbed power appeared to elevate above intensities of 150-250 W cm-2 at 1 MHz in vivo. Enhanced temperature elevations were demonstrated at the same intensity levels, with the size of the elevation increasing with intensity. This phenomenon was large enough to be useful during focussed ultrasound hyperthermia since the maximum temperature gain was about 2 degrees C when a 5 degrees C temperature elevation was induced in the tissue. Using multiple overlapping beams, this effect was further increased.
Animals↗
Errors in temperature measurement by thermocouple probes during ultrasound induced hyperthermia.
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Animals↗
The effect of thermal conduction during local hyperthermia induced by ultrasound: a phantom study.
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Hot Temperature↗
The effects of some physical factors on the production of hyperthermia by ultrasound in neoplastic tissues.
A one-dimensional and a three-dimensional computer model have been built in order to study the importance of blood flow and ultrasonic absorption in tissues during local hyperthermia. The decreased blood flow in the interior of certain tumours and possibly the increased ultrasonic absorption of the malignant tissue in some cases may cause selectively higher temperatures inside the tumours though the heat input is the same as in the surrounding tissues. Also, the vasodilation of blood vessels in normal tissues as a response to heat causes a therapeutically useful temperature difference. These blood flow differences can lead to enhanced effects during sonication to produce hyperthermia in the tumour. The inhomogeneity of blood flow in the tumour causes a non-uniform temperature distribution leaving the well-perfused cells in the advancing front at a much lower temperature than the cells in the necrotic centre. Thus, the combination of local hyperthermia with radio-and chemotherapy seems to offer the most attractive means of destroying malignant tissue.
Fever↗
Design of ultrasonic transducers for local hyperthermia.
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Acoustics↗
Erythrocyte damage caused by the Haemotherm microwave blood warmer.
Blood units (59) were warmed with the Haemotherm microwave blood warmer and seven units were warmed in a water bath for comparison. The influence of the final blood temperature, the size and the hematocrit of the units on the erythrocyte lesion was studied. Extracellular hemoglobin and potassium, hematocrit, osmotic fragility and mean cellular volume were used as indicators of red cell damage. Warming in the water bath caused no erythrocyte damage at temperatures below +46.8 degrees C. Higher temperatures caused progressive morphological changes and hemolysis. Units of red cells in saline warmed to temperatures above +46.3 degrees C with the Haemotherm showed intense hemolysis and changes in all parameters used. Below this temperature no erythrocyte damage occurred. When the amount of blood warmed was less than 300 g or when the hematocrit exceeded 0.70, the blood mixing mechanism became insufficient, leading to local overheating and hemolysis. Therefore, erythrocyte concentrates in a Fenwal blood bag should never be warmed by the Haemotherm. The mean plasma hemoglobin increase of the ten whole blood units warmed by the Haemotherm to +36.0-36.8 degrees C was 123 mg/l. The results of the present study indicate that microwaves per se are not harmful to erythrocytes but that poor penetrance of microwaves, together with insufficient blood mixing during warming, are the critical factors leading to hemolysis.
Blood Transfusion↗
On-line monitoring of ultrasonic surgery with MR imaging.
Ultrasonic surgery was performed in rabbits and dogs under the guidance of magnetic resonance (MR) imaging. Two different MR techniques were used to guide the ultrasound beam. T2-weighted images showed lesion formation within a few minutes after sonication. T1-weighted GRASS (gradient-recalled acquisition in the steady state) images were sensitive to temperature elevations, permitting monitoring of lesion creation with MR imaging. Short TR T1-weighted GRASS images were not as helpful in detecting temperature elevation because of a reduction in signal-to-noise ratio. T2-weighted fast spin-echo images were compared with conventional T2-weighted spin-echo images. The former produced high-quality images in a fraction of the imaging time. This study shows that it is possible to monitor and guide ultrasonic surgery with MR imaging.
Animals↗
MR monitoring of focused ultrasonic surgery of renal cortex: experimental and simulation studies.
The aim of the study was to test the hypothesis that magnetic resonance (MR) imaging-guided and -monitored noninvasive ultrasonic surgery can be performed in highly perfused tissues from outside the body. A simulation study was performed to evaluate the optimal sonication parameters. An MR-compatible positioning device was then used to manipulate a focused ultrasound transducer in an MR imager, which was used to sonicate kidneys of five rabbits at various power levels and different durations. Temperature elevation during sonication was monitored with a T1-weighted spoiled gradient-echo sequence. The simulation study demonstrated that a sharply focused transducer and relatively short sonication times (30 seconds or less) are necessary to prevent damage to the overlying skin and muscle tissue, which have a much lower blood perfusion rate than kidney. The experiments showed that the imaging sequence was sensitive enough to show temperature elevation during sonication, thereby indicating the location of the beam focus. Histologic evaluations showed that kidney necrosis could be consistently induced without damage to overlying skin and muscle. The study demonstrated that highly perfused tissues such as the renal cortex can be coagulated from outside the body with focused ultrasound and that MR imaging can be used to guide and monitor this surgery.
Animals↗
MRI evaluation of thermal ablation of tumors with focused ultrasound.
MRI was used to target and evaluate the tissue effects of focused ultrasound ablation on tumors implanted in the skeletal muscle of rabbits in vivo. First, MRI was used to localize the tumors and plan the ultrasound therapy. Second, temperature-sensitive phase-difference images were acquired to monitor the location of the ultrasound focus and to estimate the effects of temperature rise. After the treatment, the spatial and temporal temperature profiles for defining boundaries of tissue coagulation were calculated. Finally, these boundaries were compared to T2-weighted and contrast-enhanced T1-weighted images obtained immediately after therapy. The results indicate that using MRI for planning and evaluating focused ultrasound surgery is feasible. We showed a linear relationship between applied power and shifts in the proton resonant frequency. Fluctuations in the location of the focus about the target location were on the order of the resolution of the MR images. The temperature rise and lesion size varied significantly. Regions of tissue coagulation calculated from MR data correlated well with post-therapy imaging.
Animals↗
Brain edema development after MRI-guided focused ultrasound treatment.
The aim of this study was to investigate a potential technique for image-guided minimally invasive neurosurgical interventions. Focused ultrasound (FUS) delivers thermal energy without an invasive probe, penetrating the dura mater, entering through the cerebrospinal fluid (CSF) space, or harming intervening brain tissue. We applied continuous on-line monitoring by MRI to demonstrate the effect of the thermal intervention on the brain tissue. For this, seven rabbits had a part of their skull removed to create access for the FUS beam into the brain through an acoustic window of 11 mm in diameter. Dura was left intact and skin was sutured. One week later, the rabbits were sonicated for 3 seconds with 21 W acoustic power, and the FUS focus was visualized with a temperature-sensitive T1-weighted MRI pulse sequence. The tissue reaction was documented over 7 days with T2-weighted images of the brain. The initial area of the central low signal intensity in the axial plane was .4+/-.3 mm2, and for the bright hyperintensity surrounding the lesion, it was 2.3+/-.6 mm2 (n = 7). In the coronal plane, the corresponding values were .4+/-.1 mm2 and 3.4+/-.9 mm2 (n = 5). The developing brain edema culminated 48 hours later and thereafter diminished during the next 5 days. Histology revealed a central necrosis in the white matter surrounded by edematous tissue with inflammatory cells. In summary, the image-guided thermal ablation technique described here produced a relatively small lesion in the white matter at the targeted location. This was accomplished without opening the dura or the need for a stereotactical device. MRI allowed on-line monitoring of the lesion setting and the deposition of thermal energy and demonstrated the tissue damage after the thermal injury.
Animals↗
Calibration of water proton chemical shift with temperature for noninvasive temperature imaging during focused ultrasound surgery.
The present work was performed to calibrate water proton chemical shift change with tissue temperature in vivo to establish a method of quantitative temperature imaging during focused ultrasound surgery. The chemical shift change measured with a phase-mapping method using spoiled gradient-recalled acquisition in steady state (SPGR) (TR = 26 msec, TE = 12.8 msec, matrix = 256 x 128) was calibrated with the corresponding temperature elevation (0-50 degrees C, 32-84 degrees C in absolute temperature) measured with a copper-constantan thermocouple (.05-mm-diameter bare wires) in rabbit skeletal muscle (16 animals) under focused ultrasound exposures (10-100 W radiofrequency [RF] power, 20-second sonication). A linear calibration with a regression coefficient of (-8.76+/-.69) x 10(-3) ppm/degrees C (P < .01 [P, significance level]) was obtained. Temperature distributions during a 20-second sonication were visualized every 3.3 seconds with a 2.3-mm3 spatial resolution and 4 degrees C temperature uncertainty.
Animals↗
Tissue temperature monitoring with multiple gradient-echo imaging sequences.
The inherent sensitivity of multiple gradient-echo sequences to the chemical shift is exploited to rapidly map muscle water frequency shifts caused by ultrasonic heating. The use of multiple echoes is shown to offer several advantages over single gradient-echo approaches previously proposed for temperature measurement. An increase in the effective bandwidth significantly reduces aliasing problems observed with single gradient-echo methods in high temperature applications. Of greater significance is the improved immunity to intrascan motion found for multi-echo versus single echo gradient methods, making the former more attractive for clinical applications. Finally, a sensitivity to the presence of multiple spectral components unavailable with single gradient-echo methods is obtained.
Animals↗
Local hyperthermia induced by focussed and overlapping ultrasonic fields--an in vivo demonstration.
Axial temperature distributions were measured in living and post mortem porcine tissues during sonication with plane, focussed and overlapping ultrasonic fields. With the focussed field it was always possible to induce the temperature maxima at depths up to 50 mm, although the actual temperatures achieved varied from animal to animal. The plane 0.75 MHz transducer produced a maximum temperature close to the skin surface. With 7 overlapping plane fields a relatively uniform temperature distribution was produced in a large tissue volume. The blood perfusion in tissue has a significant effect not only on the magnitude of the temperature increase, but also on the temperature distribution.
Animals↗
The construction and assessment of lenses for local treatment of malignant tumours by ultrasound.
A simple method to build ultrasound lenses from araldite has been developed. The focussing properties of these lenses as a function of sonic frequency and lens diameter were studied using a computer model. The optimum frequency and diameter of these lens were found to be around 1 MHz and between 40 and 60 mm respectively, for deep tissue heating. The stability of the power output as well as the temperature distributions produced in vitro and in vivo have also been studied. It appears to be possible to produce larger temperature elevations near the acoustical focus than near the skin surface in vivo. Therefore the lenses seem to be suitable for local cancer treatment.
Animals↗
Measurement of ultrasound energy density distributions in vivo.
Thermocouple junctions coated with absorbing material have been used for measurement of ultrasound energy density distribution in vivo. The response of this type of probe has been measured in tumours implanted in rats, in ox liver, and in a water bath, using 1 and 3 MHz focussed ultrasound, and these measurements are reported in this paper. The initial rapid rate of temperature rise during the first 60 ms after the ultrasound is switched on provides a reliable index of ultrasound energy density. The coating material increases the magnitude of the temperature rise and reduces variations caused by differences in tissue properties and changes in blood flow. The response is a linear function of ultrasound energy density over the range of interest for therapeutic applications. Thus probes calibrated in known ultrasound fields in water tanks can be used to estimate energy densities in tissue directly.
Animals↗
Control system for an MRI compatible intracavitary ultrasound array for thermal treatment of prostate disease.
A 16-channel ultrasound intracavitary array is currently being used in a clinical setting for localized hyperthermia treatment of prostate tumours. Currently, the individual power to each array element is adjusted based on the clinician's judgement of the temperature measured at the locations of invasive thermocouple probes. MRI-derived temperature measurements may be useful for a feedback control system that non-invasively regulates the temperature distribution by adjusting the power to the elements of the array. MRI has been shown to provide accurate, high resolution, non-invasive thermometry. A proportional-plus-integral, single-input, single-output controller was designed to evaluate the feasibility of MRI-derived temperature feedback with this applicator. Input parameters for the controller were determined by modelling the tissue response to the heating from the array. Ex vivo and in vivo experiments evaluated the ability of the MRI-based temperature feedback control system to achieve and maintain a target temperature for a sustained period similar to that of a clinical hyperthermia treatment. With the controller set to a reference temperature of 43 degrees C and a rise time of 6 min, the temperatures within the ex vivo tissue (n = 6) were 43.1 +/- 0.3 degrees C after reaching the reference temperature and had a rise time of 9.5 +/- 0.3 min. In vivo results using rabbit thigh muscle (n = 7) showed that the steady state temperatures were within +/- 1 degree C of their target temperatures. These results demonstrated the feasibility of a temperature feedback for controlling the heating from an intracavitary transrectal array based on temperature information from MR images.
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