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Thin-layer liquid crystal thermometry of cells in vitro during hyperthermal microwave irradiation.

A nonperturbing technique of thin-layer liquid crystal thermometry was developed to quantitate heating of Chinese hamster ovary cells and the bacterium Serratia marcescens when exposed to 2450-MHz microwave fields at 0.2-0.5 W/cm2. Cells suspended in culture medium were injected into 5-cm glass microcapillary tubes coated on the inside with a thin layer of liquid crystal. The tubes were sealed and placed parallel to the electric field in a watertight waveguide exposure chamber where they were heated by circulating temperature-controlled water. Even at high circulation rates, liquid crystal color changes indicated local microwave capillary tube heating of 0.1-0.25 degrees C. Precision of measurement was 0.02 degrees C. Observations during microwave heating were significantly different from observations without microwaves at the 1% level, and heating increased as circulating water flow was reduced from 300 ml/s to 100 ml/s. The results of a cell survival assay following hyperthermal treatment were in good agreement with expectations based on the observations of microwave heating using liquid crystals.

Animals↗

Tissue thermal conductivity by magnetic resonance thermometry and focused ultrasound heating.

PURPOSE: To investigate the combined use of magnetic resonance (MR) temperature imaging and focused ultrasound (FUS) for the noninvasive determination of tissue thermal properties. MATERIALS AND METHODS: Brief, spatial impulses of temperature elevation were created in tissue using a spherical, air-backed transducer operating at 1.68 MHz and measured using MR temperature imaging in a 1.5-Tesla clinical scanner. A novel technique based on thermal washout is applied in an analysis of the acquired MR temperature images to estimate tissue thermal conductivity and perfusion. RESULTS: Numerical simulations and experiments in vitro and in vivo demonstrate that thermal conductivity can be measured to within 10% of the true value with MR thermometry at 1.5 Tesla. With the temperature precision available at 1.5 Tesla, however, robust perfusion estimation is feasible only in highly perfused organs or tumors. CONCLUSION: This study has developed a method for determining tissue thermal properties specific to the patient and organ at the site of interest, and allows repeated application. This capability is relevant in thermal therapy planning of tumor ablation using MR-guided FUS systems.

Animals↗

Use of fast spin echo for phase shift magnetic resonance thermometry.

PURPOSE: To propose a modified fast spin echo (FSE) magnetic resonance imaging sequence for MR thermometry, employing the proton resonance frequency (PRF) shift by means of MR phase maps. Despite their obvious advantages of speed and high signal-to-noise ratio (SNR), FSE sequences have not until now been used for this purpose due to the restraints imposed by the Carr-Purcell-Meiboom-Gill (CPMG) conditions. MATERIALS AND METHODS: The new FSE combines a new phase modulation scheme that maintains magnetization that ordinarily is destroyed under CPMG conditions, while employing conventional FSE gradient waveforms. The echoes are read in a single shot using 128 readouts in 650 msec, with a phase sensitive preparation using an optional time shift tau before the start of the refocusing gradient waveforms. This feature allows the quantification of temperature dependent phase shifts. We tested the sequence by imaging a heated agar gel phantom while cooling, using different values for tau. RESULTS: There was good correlation between FSE and fiberoptic-based temperature measurements in the phantom(r(2) >or= 0.95). Temperature sensitivity could be adjusted by varying the tau value. CONCLUSION: With the proposed non-CPMG FSE sequence it is feasible to quantify temperature changes by means of the PRF shift.

Humans↗

Noninvasive MRI thermometry with the proton resonance frequency (PRF) method: in vivo results in human muscle.

The noninvasive thermometry method is based on the temperature dependence of the proton resonance frequency (PRF). High-quality temperature images can be obtained from phase information of standard gradient-echo sequences with an accuracy of 0.2 degrees C in phantoms. This work was focused on the in vivo capabilities of this method. An experimental setup was designed that allows a qualitative in vivo verification. The lower-leg muscles of a volunteer were cooled and afterwards reheated with an external water bolus. The temperature of the bolus water varied between 17 degrees C and 37 degrees C. The in vivo temperature images can be used to extract the temperature in muscle tissue. The data in the fat tissue are difficult to interpret because of the predominance of susceptibility effects. The results confirm the method's potential for hyperthermia control.

Algorithms↗

Noninvasive MRI thermometry with the proton resonance frequency method: study of susceptibility effects.

The temperature dependence of proton resonance frequency (PRF) is related to the temperature dependence of the screening constant and of the volume susceptibility constant. To evaluate the relative importance, an experimental setup was designed allowing quantification of both effects in different tissues, notably pure water in a gel structure, and porcine muscle and fat tissue. The temperature varied from 28 to 44 degrees C, a range significant for hyperthermia applications. Good agreement with results from the literature was obtained for water. Porcine muscle tissue behaves like water. Its screening constant varies linearly at a rate of 0.97 10(-8) (degree C)-1 and the effects of temperature-induced changes of the susceptibility constant are negligible for muscle thermometry applications. The PRF-temperature relation in fat tissue, however, is almost completely determined by susceptibility effects.

Adipose Tissue↗

Referenceless PRF shift thermometry.

The proton resonance frequency (PRF) shift provides a means of measuring temperature changes during minimally invasive thermotherapy. However, conventional PRF thermometry relies on the subtraction of baseline images, which makes it sensitive to tissue motion and frequency drift during the course of treatment. In this study, a new method is presented that eliminates these problems by estimating the background phase from each acquired image phase. In this referenceless method, a polynomial is fit to the background phase outside the heated region in a weighted least-squares fit. Extrapolation of the polynomial to the heated region serves as the background phase estimate, which is then subtracted from the actual phase. The referenceless method is demonstrated on a phantom during laser heating, 0 degrees temperature rise images of in vivo human liver, interstitial laser ablation of porcine liver, and transurethral ultrasound ablation of canine prostate. A good correlation between temperature maps reconstructed with the referenceless and subtraction methods was found.

Animals↗

Automatic spatial and temporal temperature control for MR-guided focused ultrasound using fast 3D MR thermometry and multispiral trajectory of the focal point.

Of the different modalities to induce local hyperthermia, focused ultrasound is the only noninvasive technology available at the moment. In addition to the 3D localization of the target region, it has been shown that MRI can provide real-time thermometry and allows online, automatic control of temperature evolution of the focal point. Treatment of a large tissue volume (as compared to the focal spot size, i.e., the ultrasound wavelength) can be achieved rapidly by moving the focal point along an inside-out spiral trajectory. It has been shown previously that under linear conditions of energy deposition versus temperature, the spatial profile of the temperature within a large area can be controlled. In this study, a proportional, integral, and derivative (PID) spatial-and-temporal controller is described for the control of the temperature evolution within the target region under more variable conditions. The aim was to reach a predefined temperature profile after a few successive trajectories. Heat conduction in tissue is exploited to obtain a uniform temperature increase in a volume using discrete sonications without any waiting time. Input data sets consisted of 3D temperature maps provided online by a MR scanner. For each new trajectory, the controller recalculates the number of sonications per surface unit (spatial density of points describing the trajectory) and the applied power. Its performance was tested ex vivo and in vivo. Diameters of the target region ranged from 9 mm to 19 mm. Targeted temperature increase ranged from +8 degrees C to +18 degrees C. Spatiotemporal temperature control showed good stability and fast convergence, for both circular and elliptic ROIs.

Algorithms↗

Optimization of self-reference thermometry using complex field estimation.

Referenceless, or self-reference, thermometry is a technique for mapping temperature differences in the region of interest (ROI) using the baseline phase estimated by extrapolating the field in the surrounding region for estimation (RFE) and subtracting the estimated baseline from the measured field. In the present work a self-reference technique based on complex field estimation using 2D polynomials comprising complex-valued coefficients was proposed and optimized. Numerical simulations with a Gaussian-profiled phase distribution demonstrated that the ROI radius had to be 2.3-2.5 times the standard deviation (SD) of the Gaussian function in order to keep the error below 8% of the peak phase change. The area ratio between the ROI and the RFE had to be larger than 2.0 to maintain the error level. Based on the simulations, and phantom and volunteer experiments, the complex-based method with independently optimized polynomial orders for the two spatial dimensions was compared with the phase-based method using the similar-order optimization strategy. The complex-based method appeared to be useful when phase unwrapping was not removed. Otherwise, the phase-based method yielded equivalent results with less polynomial orders.

Body Temperature↗

Inter-frame motion correction for MR thermometry.

Noninvasive temperature measurement is feasible with MRI to monitor changes in thermal therapy. Phase shift based MR thermometry gives an estimate of the relative temperature variation between thermal and baseline images. This technique is limited, however, when applied on targets under inter-frame motion. Simple image registration and subtraction are not adequate to recover the temperature properly since the phase shift due to temperature changes is corrupted by an unwanted phase shift. In this work, the unwanted phase shift is predicted from the raw registered phase shift map itself. To estimate the unwanted phase shift, a thin plate smoothing spline is fitted to the values outside the heated region. The spline value in the heated area serves as an estimate for the offset. The estimation result is applied to correct errors in the temperature maps of an ex-vivo experiment.

Algorithms↗

Grip strength test and infrared thermometry as non-invasive methods to complement acute toxicity data in mice.

Acute toxicity testing in-vivo seeks a new approach minimising the number of animals used and increasing the number of quantitative and qualitative observations. The measurement of grip strength of mice (forelimbs), a classical tool for the evaluation of muscular force and the emitted heat measurement, as a tool for evaluation of basic metabolism, have been used. The aim of acute toxicity was, up to now, to determine LD50 level or eventually a minimal lethal dose. These non-invasive tests give an idea of general health condition and allow the determination of the minimal toxic dose while in the search for the minimal lethal dose. A computer-assisted grip strength test and an infrared thermometry test have been developed and calibrated with Na+ pentobarbital, theophylline and diazepam given once orally or intraperitoneally to 10 male NMRI (MAI) mice/dose. The tests were performed within one hour after administration and daily until the values of the surviving animals went back to normal. Dose-response curves were obtained and plotted against control animals (n = 10). Oral and intraperitoneal administration in ascending doses of Na+-pentobarbital, theophylline and diazepam (i.p. only) up to the lethal level have a parallel influence on grip strength and heat emission; the correlation with mortality is clear for Na+-pentobarbital and diazepam but not for theophylline.

Animals↗

Non-invasive transcranial high intensity focused ultrasound (HIFUS) under MRI thermometry and guidance in the treatment of brain lesions.

Non-invasive transcranial high intensity focused ultrasound (HIFUS) therapy given under MRI thermometry and image guidance to awake patients lying within the bore of a 1.5 T MRI scanner (a) to thermally ablate brain lesions such as metastases, (b) to cause precise ablative brain lesions in functional disorders, or (c) to locally open the blood-brain-barrier for targeted therapeutic construct delivery--without the radiation risks of stereotactic radiotherapy--may sound science fiction. Kullervo Hynynen, a Finnish-born ultrasound and MRI physicist, and Ferenc Jolesz, a Hungarian-born neurosurgeon and visionary of image guided surgery, have joined forces at Radiology, Brigham & Women's Hospital, Boston, and they have taken every step to realize the vision above, in highly successful collaboration with the industry (GE, InSightec, TxSonics). The sophisticated transcranial HIFUS instrumentation, supported by profound research data from experimental animals and by the clinical experience from extracranial HIFUS targets (breast fibroadenoma, uterine fibroid), is now coming to a phase I clinical trial in cerebral metastases. It remains to be seen whether transcranial HIFUS will find applications in diffuse gliomas such as (a) thermal ablation of selected areas of glioma tissue, (b) opening the blood-brain-barrier for therapeutic constructs to enter selected areas, or (c) activating such constructs in desired areas. The prophecy of Dr. Jolesz, "this technology will put neurosurgeons out of business", may not fulfill during our lifetime.

Adult↗

Diagnostic value of finger thermometry and photoplethysmography in the assessment of hand-arm vibration syndrome.

Digital photoplethysmography and skin thermometry are both measures of circulation in the skin of the fingers. These methods and a cold provocation test were performed on 29 chain-saw workers grouped in stages 0, 1, 2, or 3 according to the Stockholm Workshop scale of hand-arm vibration syndrome, and on 16 controls. The reduction of photoplethysmographic amplitude after the cold test reflects the degree of vasoconstriction, and the recovery rate demonstrates passive vasodilatative capacity. Both tests were found to distinguish all vibration--exposed subjects, including those without clinically manifest vibration-induced white fingers, from the controls. With a 75% reduction in photoplethysmographic amplitude as a discriminating threshold, the sensitivity for the detection of Raynaud's phenomenon was 62% and the specificity, 87%. The discriminating threshold of 90% for recovery rate yielded a sensitivity of 69% and a specificity of 72%.

Adult↗

How should body heat storage be determined in humans: by thermometry or calorimetry?

The aim of this study was to determine whether in humans there are differences in the heat storage calculated by partitional calorimetry (S, the balance of heat gains and heat losses) compared to the heat storage obtained by conventional methods (thermometry) via either core temperature or mean body temperatures (Tb = 0.8Tc + 0.2Tsk, where Tc is core temperature and Tsk is mean skin temperature) when two different sites are used as an index of Tc [rectal (T(re)) and auditory canal (T(ac)) temperatures]. Since women respond to the heat differently than men, both sexes were studied. After a stabilisation period at thermal neutrality, six men and seven women were exposed to a globe temperature of 50 degrees C, relative humidity of 17% and wind speed of 0.8-1.0 m.s-1 for 90 min semi-nude at rest, where T(re), T(ac), Tsk, metabolic rate, dry (radiant + convective heat exchange) and evaporative heat losses, S, heat storage by Tc (STc) and heat storage by Tb (STb) were assessed every minute. In the mean, S was equal to 350.8(SEM 49.6) kJ whereas STc amounted to only 114.6(SEM 16.2) and 196.7(SEM 32.3) kJ for T(re) and T(ac), respectively (P less than 0.05). Final STb(re) underestimated S by 49% [177.7(SEM 23.0) kJ; P less than 0.05] whereas STb(ac) was not significantly different than S [255.7(SEM 37.9) kJ]. In the women, S corresponded to a total of 294.3(SEM 23.2) kJ, a value that was very similar to the STb(ac) [262.6(SEM 31.0) kJ], whereas STb(re) under-predicated S by 35% [190.4(SEM 26.3) kJ; P less than 0.05].(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Thermometry and dosimetry of heat with specific reference to the liquid-crystal optical fiber temperature probe.

A temperature sensing probe was designed utilizing the unique optical properties of thermotropic liquid crystals. An electronic and fiberoptic system coupled to the sensor was used to monitor temperature-dependent interactions of light (660 nm) with the liquid crystal mixture. The probe is a nonmetallic, nonperturbing thermal sensor for continuous temperature measurements of biological specimens subjected to electromagnetic fields. The advantages and disadvantages of the Liquid Crystal Optical Fiber (LCOF) temperature probe are discussed along with some typical applications where accurate dosimetry and thermometry are important parameters in experimental studies.

Animals↗

Effect of the status after ear surgery and ear pathology on the results of infrared tympanic thermometry.

Most publications that deal with infrared tympanic thermometry (ITT) have performed a comparison between the established temperature measurements and ITT. However, to date an understanding of the influence of pathological ear findings on ITT test results is incomplete. Therefore, in the present study ITT was performed in healthy adults (n =21), adult patients with monaural central perforation (n =31) or strong scar formations (n =24) of the tympanic membrane and 18 adult patients after monaural canal wall down surgery. Right and left ear and oral temperature were measured three times by one investigator in a room with a constant temperature of 20-22 degrees C. Between every measurement there was a free time interval of 2 min. In healthy adults (36.50 degrees C vs. 36.51 degrees C) patients with monaural central perforation of the tympanic membrane (36.41 degrees C vs. 36.34 degrees C) and with monaural strong scar formations in the tympanic membrane (36.39 degrees C vs. 36.45 degrees C), no significant difference between the right and left ear could be proved. In contrast to this, a significantly higher temperature in the surgically treated ear compared to the healthy side (36.97 degrees C vs. 36.31 degrees C; P <0.001) occurred in patients with a status of after monaural canal wall down surgery. In summary, it could be demonstrated that, in contrast to minor ear surgery, major ear surgery such as canal wall down has a significant influence on the results of ITT. If a patient's history gives reference to previous ear surgery, an otoscopic examination is necessary in order to exclude the presence of an after-canal-wall-down surgery status and thus to avoid false ITT test results.

Adult↗

An improved estimation of mean body temperature using combined direct calorimetry and thermometry.

The conventional method used to estimate the change in mean body temperature (dMBT) is by taking X% of a body core temperature and (1-X)% of weighted mean skin temperature, the value of X being dependent upon ambient temperature. This technique is used widely, despite opposition from calorimetrists. In the present paper we attempt to provide a better method. Minute-by-minute changes in dMBT, as assessed using calorimetry, and 21 (20 if esophageal temperature was unavailable) various regional temperatures (dRBTs), as assessed using thermometry, including 6 subcutaneous measures, were collected from 7 young male adults at 6 calorimeter temperatures. Since a calorimeter measures only changes in heat storage, which can be converted to dMBT, all body temperatures are expressed as changes from the reasonably constant pre-exposure temperatures. The following three aspects were investigated. (1) The prediction of dMBT from the 21 (or 20) dRBTs with multi-linear regression analysis (MLR). This yields two results, model A with rectal temperature (dTre) alone, and model B with dTre and esophageal temperature (dTes). (2) The prediction of dMBT from dTre with or without dTes and 13 skin surface temperatures combined to one weighted mean skin temperature (dTsk), using MLR. This results in models C and D. Six more models (E-J) were added, representing the above two sets in various combinations with four factors. (3) The conventional method calculated with four values for X. Model A predicted better than 0.3 degree C in 70% of the cases. Model I was the best amongst the models with 13 weighted skin temperatures (better than 0.3 degree C in 60% of the cases). The conventional method was erratic.

Adult↗

Design and thermometry of an intracavitary microwave applicator suitable for treatment of some vaginal and rectal cancers.

The construction of a modified coaxial cable as an intracavitary microwave applicator suitable for use in some vaginal and rectal cancers is presented. Thermometry was performed for microwave frequencies of 300, 400, 650, and 915 MHz. Temperature profiles in tissue phantoms were obtained with non-perturbing temperature probes and thermography, and the data were compared with those obtained in dogs. The temperature profiles were dependent on the frequency of the microwaves and the insertion depth of the applicator. In addition, an acrylic cylindrical spacer external to the applicator also altered the heating pattern. Therefore, with proper combinations of frequency, insertion depth and spacer, the applicator can be used for heating tumors in some clinical situations.

Animals↗

Hyperthermia thermometry evaluation: criteria and guidelines.

Results of the evaluation of thermometry devices used during hyperthermia treatments at 14 different clinics in the USA are presented. Measurements were made by the Hyperthermia Physics Center (HPC, a national hyperthermia quality assurance program under NCI contract No. N01-CM-37512) according to a protocol. Our sample included thermocouples, fiberoptic thermometers, and high lead resistance thermistors. We found that only some but not all of the thermometers of each kind performed within the +/- 0.2 degrees C acceptability criteria of accuracy. The precision, stability, and response times achieved with each type of thermometer are presented. A summary of perturbations and artifacts typical for each system is presented together with suggested precautions to avoid them during clinical usage. We conclude that although the technology used with each thermometer system is capable of producing a temperature accuracy of 0.2 degrees C, this accuracy is clinically achievable only with a concerted effort and a constant alertness on the part of the investigator. Based on the combined experience of this survey, the clinical investigators we visited, and published reports, we present certain guidelines and procedures that can help to reduce the inaccuracies and improve the reliability of temperature data obtained in clinical hyperthermia trials.

Fiber Optic Technology↗