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Non-invasive magnetic resonance thermometry using thulium-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetate (TmDOTA(-)).

Non-invasive thermometry is pivotal to the future advances of regional hyperthermia as a cancer treatment modality. Current magnetic resonance (MR) thermometry methods suffer from poor thermal resolution due to relatively weak dependence of chemical shift of the (1)H water signal on temperature. This study evaluated the feasibility of using thulium-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetate (TmDOTA(-)) for MR thermometry. TmDOTA(-) is non-toxic and the gadolinium complex of DOTA(4-) is widely used as a MR contrast agent. The results demonstrate that the temperature dependence of the TmDOTA(-) proton shifts are about two orders of magnitudes higher than the water proton and, thus, provide excellent accuracy and resolution. In addition, TmDOTA(-) proton shifts are insensitive to the paramagnetic complex concentration, pH, Ca(2+) or presence of plasma macromolecules and ions. Because hyperthermia is known to produce changes in tissue pH and other physiological parameters, these properties of TmDOTA(-) greatly simplify the procedures for using the lanthanide complex for MR thermometry. Application of TmDOTA(-) for measurement of temperature in a subcutaneously implanted human melanoma xenograft is demonstrated. Finally, the feasibility of imaging one of the (1)H resonances of the lanthanide complex is demonstrated in phantom experiments. Overall, TmDOTA(-) appears to be a promising probe for MR thermometry in vivo.

Animals↗

Intra-luminal thermometry: is tissue type assignment a necessity for thermal analysis?

INTRODUCTION: Tissue type assignment, i.e. differentiation tumour from normal tissue, is a normal procedure for interstitial thermometry. In our department, thermometry in patients with a tumour in the lower pelvis is usually restricted to the intra-luminal tracks. It is unknown whether discrimination between normal and tumour tissue is relevant for deep regional hyperthermia thermal dosimetry using only intra-luminal tumour contact and tumour adjacent thermometry. This study has analysed the acquired temperature data in order to answer this question. PATIENTS AND METHODS: Seventy-five patients with locally advanced cervical carcinoma were selected randomly. Patients were treated with a two or three modality combination, i.e. radiotherapy +hyperthermia or radiotherapy + hyperthermia + chemotherapy from October 1997 to September 2003. The first 100 hyperthermia treatments fulfilling the only selection criterion: no displacement of the thermometry catheter along the insertion length during the treatment, were included in the study, resulting in 43 patients with one-to-five treatments/patient (median 2). Using RHyThM (Rotterdam Hyperthermia Thermal Modulator), for each single treatment tissue type, was defined on the basis of information given by a CT scan in radiotherapy position. A step change in the slope of the profile of the first temperature map was identified to verify the insertion length of the catheter. RESULTS: The average T50 (median temperature) in bladder tumour indicative, vagina tumour contact and rectum tumour indicative was 40.9 +/- 0.9 degrees C, 39.7 +/- 0.9 degrees C and 40.6 +/- 0.8 degrees C, respectively. The average normal tissue T50 in bladder, vagina and rectum was 40.8 +/- 0.9 degrees C, 40.1 +/- 0.9 degrees C and 40.7 +/- 0.8 degrees C, respectively. The differences between bladder tumour indicative T50 and bladder normal tissue T50 and also between vagina tumour contact T50 and vagina normal tissue T50 were significant ( p = 0.0001). No statistical difference was found between rectum tumour indicative t50 and rectum normal tissue T50. CONCLUSION: At present the cause of the temperature difference is not known. However, as the difference between tumour (indicative/contact) and normal tissue is very small and considering also the inaccuracy in the tissue type assignment it can be stated that this study does not provide sufficient evidence to conclude that the statistical difference has clinical relevance. Therefore, it was concluded that at this time there is no need to differentiate between normal and tumour tissue in intra-luminal thermometry.

Antineoplastic Agents↗

Cost effectiveness of tympanic thermometry in the pediatric office setting.

This study was designed to see if tympanic thermometry might be more cost effective than cheaper more traditional methods of thermometry when office staff time saved is taken into account. There were 224 patients enrolled from three private pediatric practices. Patients were alternately assigned to have their temperature taken with either a tympanic thermometer or with a rectal or oral thermometer depending on the patient's age. For each child enrolled in the study a nurse was asked to time the temperature taking process. Items included in the cost analysis: a) thermometer costs; b) disposable supply costs; c) personnel costs; d) equipment service costs. The mean duration of temperature taking was 35.2 seconds using tympanic thermometers, 73.4 seconds using electronic predictive thermometers, and 247.2 seconds using glass thermometers. In practices taking an average of 10 temperatures per day, tympanic thermometry saved $2,316/year when compared to glass thermometers and $442/year when compared to electronic predictive thermometers. The data presented in this study show that when nursing time is taken into account, tympanic thermometry is less expensive to perform than traditional methods of thermometry despite the initial higher cost of the thermometer.

Body Temperature↗

[Thermometry of cadavers].

The purpose of this study was to analyze the norm-setting documents on the order of thermometry, regulating the steps of physician during examination at the site where the cadaver was found and of medical expert during expert evaluations and to disclose the relationship between the depth to which the thermometer is inserted during measurements of rectal temperature and thermometry value. The following conclusions are made: 1) even at the same time of death, the data of rectal thermometry are in direct proportion to the depth to which the thermometer is inserted into the rectum; 2) some assumptions in the norm-setting documents regulating the order of cadaver thermometry are to be revised; and 3) thermometers and method of thermometry performed by medical specialists at the site of accident and by experts at thanatological departments of Bureaus of Forensic Medical Expert Evaluations are to be standardized.

Body Temperature↗

The use of infrared thermometry for the detection of fever.

The use of tympanic thermometry is attractive in primary care, but a recent systematic review highlighted the paucity of data comparing tympanic thermometry with conventional methods. We report a study of 94 preschool children presenting to primary care in the United Kingdom (UK) with acute cough in whom tympanic infrared and axillary mercury thermometry are compared. Infrared thermometry showed poor agreement, poor sensitivity and high specificity. Infrared thermometry is too insensitive to be used as a screening test for fever, but when fever is already suspected, for example by touch, it may be useful as a 'rule in' test.

Axilla↗

[Infrared tympanic thermometry. Experience and training does not improve the quality of measurement results].

Nurses, with and without training in the use of infrared tympanic thermometry, performed measurement sequences on patients. One rectal and two repeated measurements with each of two types of equipment for infrared tympanic thermometry (Genius, Core Check) were used in each sequence. Rectal measurements showed temperatures significantly higher than infrared tympanic thermometry, but there were variations (Genius 0.3 +/- 0.58 (SD) degree C, Core Check 0.5 +/- 0.42 (SD) degree C). The sensitivity of infrared tympanic thermometry for fever, as defined by rectal measurements, was 36% for Genius and 21% for Core Check. The quality of the measurements was not improved by training. Our results indicate that infrared tympanic thermometry should be used with caution when screening for fever in hospitals.

Adult↗

[Comparative study of tympanic and mercury thermometry in children].

The aim of the study was to evaluate tympanic thermometry when compared with conventional glass-mercury thermometry, in 186 consecutive pediatric patients. In patients of less than 6 years of age (n = 120), there were no differences between tympanic and rectal measurements, in febrile and afebrile ranges, and significantly different when compared with axillary range. Similar data were reported in children of more than than 6 years of age (n = 65), in whom oral temperatures replace the rectal one. Using the tympanic thermometer as the standard measurement device, the accuracy of rectal, oral and axillary thermometers in determining a febrile state was examined. When tympanic temperature was 38 degrees C, a febrile state was considered, in this condition sensitivity for rectal measurement was of 73%, for oral 64%, and 23 and 29% for the axillary, according to the age group: specificity was of 100% in all the them. According to our data, tympanic measurement was consistent with glass-mercurial, rectal and oral, temperature in a pediatric population. Advantages of tympanic thermometry are its good correlation with central temperature, substantial time reduction of measurement (1 second), easy and non-invasive procedure, improved patient comfort, and lack of mercurial thermometry disadvantages. The conclusion is that tympanic thermometry becomes an acceptable option for pediatric temperature measurement.

Adolescent↗

Noninvasive MR thermometry using paramagnetic lanthanide complexes of 1,4,7,10-tetraazacyclodoecane-alpha,alpha',alpha'',alpha'''-tetramethyl-1,4,7,10-tetraacetic acid (DOTMA4-).

Noninvasive techniques to monitor temperature have numerous useful biomedical applications. However, MR thermometry techniques based on the chemical shift, relaxation rates, and molecular diffusion rate of the water 1H signal suffer from poor thermal resolution. The feasibility of MR thermometry based on the strong temperature dependence of the hyperfine-shifted 1H signal from the paramagnetic lanthanide complex thulium-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetate (TmDOTA-) was recently demonstrated. The use of paramagnetic lanthanide complexes for MR thermometry can be further enhanced by improving the signal-to-noise ratio (SNR) of the observed signal. In this study, the use of lanthanide complexes of a methyl-substituted analog of DOTA4-, 1,4,7,10-tetramethyl 1,4,7,10-tetra azacyclodoecane-1,4,7,10-tetraacetic acetate (DOTMA4-) was evaluated. DOTMA4- complexes have 12 magnetically equivalent methyl protons, which provide an intense and sharper resonance compared to the corresponding DOTA- complexes. Experiments with paramagnetic Pr3+, Yb3+, Tb3+, Dy3+, and Tm3+ complexes of DOTMA4- showed that the Tm3+ complex is most favorable for MR thermometery because of the high temperature dependence of its chemical shift and its relatively narrow linewidth. The chemical shift of the methyl 1H signal from TmDOTMA- was approximately 60 times more sensitive to temperature than the water 1H shift and was insensitive to changes in concentration, pH, [Ca2+], or the presence of other ions and macromolecules. The application of TmDOTMA- for measuring temperature in a subcutaneously implanted tumor model was demonstrated. Lastly, the feasibility of obtaining 3D images from the methyl 1H resonance of TmDOTMA- was demonstrated in phantom and live animal experiments. Overall, TmDOTMA- appears to be a promising probe for MR thermometry in vivo.

Algorithms↗

High dose-rate induced temperature artifacts: thermometry considerations for simultaneous interstitial thermoradiotherapy.

PURPOSE: The goal of the present study was to investigate the effect of high dose-rate radiation on a flouroptic thermometry system commonly used during microwave hyperthermia. METHODS AND MATERIALS: Measurements were performed by placing the flouroptic thermometry sensors at distances of < or = 1.5, 5, 10, and 15 mm from a remote afterloading high dose-rate 192Ir source in a water bath (at two different temperatures) and in a tissue equivalent radiation bolus medium. A simulated volumetric clinical setup using a radiation bolus medium was performed with thermometry sensors placed at 1.5, 7.5, 8.4, and 10.6 mm from a scanning high dose-rate source. RESULTS: It was found that high dose-rate radiation caused thermometry artifacts greater than 1.5 degrees C within 2 min for flouroptic thermometers placed 1.5 mm from a 5 Ci activity high dose-rate source. Simple calculations showed that artifacts of this magnitude could not be due to any heating caused by the energy deposited by the high dose-rate source. The artifact decayed, but was still evident 24 h after the exposure. The effect strongly depended on distance with a 0.7 degrees C artifactual increase in temperature seen for the probe 5 mm from the high dose-rate source. Moreover, experiments performed under conditions that represented a clinical setup with a 7 Ci high dose-rate source showed that for exposure times of 10 s, at distances of 1.5 mm, significant artifacts (> 0.5 degrees C) are produced. CONCLUSIONS: These findings indicate that high dose-rate-induced temperature artifacts should be taken into account in the quality assurance procedures for the treatment of patients with simultaneous interstitial thermoradiotherapy.

Artifacts↗

Comparison of laser Doppler flowmetry and thermometry in the postoperative monitoring of replantations.

Reliable postoperative monitoring in microvascular surgery is necessary to improve the success rate of reexplorations following vascular compromise. Surface thermometry is known as an easy and inexpensive objective postoperative monitor and therefore is used by many microsurgeons. Reliability, however, is not satisfactory, and therefore several other instrumental methods have been tested of which laser Doppler flowmetry shows the most promising results. This study compared laser Doppler flowmetry to thermometry in the postoperative monitoring after replantation surgery. In 34 patients, 45 replantations and revascularizations were monitored by laser Doppler flowmetry and thermometry. A reliable alarm value of 10 PU was defined for replantations and revascularizations, with a sensitivity of 93% and a specificity of 94%. Thermometry showed a sensitivity of 84% and a specificity of 86% at 29 degrees C.

Adolescent↗

Implications of using thermocouple thermometry in 27 MHz capacitively coupled interstitial hyperthermia.

The 27 MHz Multi Electrode Current Source (MECS) interstitial hyperthermia system uses segmented electrodes, 10-20 mm long, to steer the 3D power deposition. This power control at a scale of 1-2 cm requires detailed and accurate temperature feedback data. To this end seven-point thermocouples are integrated into the probes. The aim of this work was to evaluate the feasibility and reliability of integrated thermometry in the 27 MHz MECS system, with special attention to the interference between electrode and thermometry and its effect on system performance. We investigated the impact of a seven-sensor thermocouple probe (outer diameter 150 microns) on the apparent impedance and power output of a 20 mm dual electrode (O.D. 1.5 mm) in a polyethylene catheter in a muscle equivalent medium (sigma 1 = 0.6 S m-1). The cross coupling between electrode and thermocouple was found to be small (1-2 pF) and to cause no problems in the dual-electrode mode, and only minimal problems in the single-electrode mode. Power loss into the thermometry system can be prevented using simple filters. The temperature readings are reliable and representative of the actual tissue temperature around the electrode. Self-heating effects, occurring in some catheter materials, are eliminated by sampling the temperature after a short power-off interval. We conclude that integrated thermocouple thermometry is compatible with 27 MHz capacitively coupled interstitial hyperthermia. The performance of the system is not affected and the temperatures measured are a reliable indication of the maximum tissue temperatures.

Electrodes↗

Adoption of thermometry into clinical practice in the United States.

Technologic advances in thermometer design and conceptual advances in the understanding of homeostasis between 1700 and 1850 led to recognition of the usefulness of measuring body temperature in human disease. These advances took place in Europe and Great Britain, culminating in the publication in 1868 of the seminal work on fever in human disease by Carl Wunderlich. In the United States thermometry was popularized by a number of distinguished American physicians who used European data that had appeared in British and American journals even before 1868. Thus Edward Seguin and Austin Flint included fever curves and vital signs in articles that appeared in 1866. Flint and Jacob DaCosta added sections on thermometry to their medical textbooks in 1866-1867, and Edouard Seguin (the father of Edward) encouraged the use of thermometry by the public at large in a series of articles in the medical and lay press. Within just two decades thermometry became recognized as an indispensable medical tool, which it remains to the present time.

Body Temperature↗

A three-compartment thermometry model for the improved estimation of changes in body heat content.

The aim of this study was to use whole body calorimetry to directly measure the change in body heat content (DeltaH(b)) during steady-state exercise and compare these values with those estimated using thermometry. The thermometry models tested were the traditional two-compartment model of "core" and "shell" temperatures, and a three-compartment model of "core," "muscle," and "shell" temperatures; with individual compartments within each model weighted for their relative influence upon DeltaH(b) by coefficients subject to a nonnegative and a sum-to-one constraint. Fifty-two participants performed 90 min of moderate-intensity exercise (40% of Vo(2 peak)) on a cycle ergometer in the Snellen air calorimeter, at regulated air temperatures of 24 degrees C or 30 degrees C and a relative humidity of either 30% or 60%. The "core" compartment was represented by temperatures measured in the esophagus (T(es)), rectum (T(re)), and aural canal (T(au)), while the "muscle" compartment was represented by regional muscle temperature measured in the vastus lateralis (T(vl)), triceps brachii (T(tb)), and upper trapezius (T(ut)). The "shell" compartment was represented by the weighted mean of 12 skin temperatures (T(sk)). The whole body calorimetry data were used to derive optimally fitting two- and three-compartment thermometry models. The traditional two-compartment model was found to be statistically biased, systematically underestimating DeltaH(b) by 15.5% (SD 31.3) at 24 degrees C and by 35.5% (SD 21.9) at 30 degrees C. The three-compartment model showed no such bias, yielding a more precise estimate of DeltaH(b) as evidenced by a mean estimation error of 1.1% (SD 29.5) at 24 degrees C and 5.4% (SD 30.0) at 30 degrees C with an adjusted R(2) of 0.48 and 0.51, respectively. It is concluded that a major source of error in the estimation of DeltaH(b) using the traditional two-compartment thermometry model is the lack of an expression independently representing the heat storage in muscle during exercise.

Absorptiometry, Photon↗

Responses of children, parents, and nurses to tympanic thermometry in the pediatric office.

This study was designed to assess children's behavioral responses to tympanic thermometry. In addition, parents' and nurses' impressions of this new technology were evaluated. 224 patients were enrolled from three private pediatric practices. Patients were alternately assigned to have their temperature taken with either a tympanic thermometer or with a rectal or oral thermometer. Parents and nurses were then asked to fill out a short questionnaire to describe their observations of the child's behavior during temperature taking and to describe their own feelings about the temperature taking method used. Parents were also asked to assess their usual method of temperature taking at home and their child's usual behavioral response. Tympanic thermometry was rated higher by both parents and nurses for speed, ease, cleanliness, and safety. Parents and nurses were more confident in the accuracy of traditional temperature taking methods. Children whose temperatures were taken rectally were more likely to be observed by both parents (p = .02) and nurses (p = .01) to have a negative behavioral reaction to the procedure than children whose temperatures were taken by tympanic thermometry. There was no difference observed between the behavioral responses of children who had temperatures taken orally and those who had tympanic thermometry.

Adolescent↗

Closed chamber thermometry and humidity measurements in normal and dry eye patients: a pilot study.

PURPOSE: To verify the diagnostic value of closed chamber thermometry and humidity measurement in normal and dry eye patients. METHODS: In 20 patients (40 eyes) with dry eye and 20 normal sex- and age-matched controls (40 eyes), aged from 11 to 61 years (mean 37.52 yrs, standard deviation, (SD) 14.81) temperature was measured by infrared thermometry and humidity measured in a closed chamber 15 mm from the cornea. The temperature reading in degrees C and humidity in % (RH) were noted on closing and then opening the eye for five seconds. RESULTS: The temperature rose significantly, by 0.11 degrees C +/- 0.02, between the closed and open eye positions (p < 0.000) in normal eyes, but there was no change in dry eyes. The humidity in normal eyes in the closed position was 49.50 +/- 4.67% and 50.03 +/- 4.65% in the open position (p < 0.00001). Humidity in the closed and open positions in dry eyes was 52.77 +/- 7.13% and 53.59 +/- 6.75% (p < 0.00000). The difference between closed and open dry eyes was 1.25 +/- 0.40%, compared to 0.54 +/- 0.20% in normal controls (p < 0.005). No relationship was found with age or sex. CONCLUSIONS: Thermometry and humidity measurements in a dry eye patient had a 100% diagnostic value. The reading of no change in thermometry and more than 1% change in humidity were highly diagnostic of dry eyes.

Adolescent↗

MR thermometry characterization of a hyperthermia ultrasound array designed using the k-space computational method.

BACKGROUND: Ultrasound induced hyperthermia is a useful adjuvant to radiation therapy in the treatment of prostate cancer. A uniform thermal dose (43 degrees C for 30 minutes) is required within the targeted cancerous volume for effective therapy. This requires specific ultrasound phased array design and appropriate thermometry method. Inhomogeneous, acoustical, three-dimensional (3D) prostate models and economical computational methods provide necessary tools to predict the appropriate shape of hyperthermia phased arrays for better focusing. This research utilizes the k-space computational method and a 3D human prostate model to design an intracavitary ultrasound probe for hyperthermia treatment of prostate cancer. Evaluation of the probe includes ex vivo and in vivo controlled hyperthermia experiments using the noninvasive magnetic resonance imaging (MRI) thermometry. METHODS: A 3D acoustical prostate model was created using photographic data from the Visible Human Project. The k-space computational method was used on this coarse grid and inhomogeneous tissue model to simulate the steady state pressure wavefield of the designed phased array using the linear acoustic wave equation. To ensure the uniformity and spread of the pressure in the length of the array, and the focusing capability in the width of the array, the equally-sized elements of the 4 x 20 elements phased array were 1 x 14 mm. A probe was constructed according to the design in simulation using lead zerconate titanate (PZT-8) ceramic and a Delrin plastic housing. Noninvasive MRI thermometry and a switching feedback controller were used to accomplish ex vivo and in vivo hyperthermia evaluations of the probe. RESULTS: Both exposimetry and k-space simulation results demonstrated acceptable agreement within 9%. With a desired temperature plateau of 43.0 degrees C, ex vivo and in vivo controlled hyperthermia experiments showed that the MRI temperature at the steady state was 42.9 +/- 0.38 degrees C and 43.1 +/- 0.80 degrees C, respectively, for 20 minutes of heating. CONCLUSION: Unlike conventional computational methods, the k-space method provides a powerful tool to predict pressure wavefield in large scale, 3D, inhomogeneous and coarse grid tissue models. Noninvasive MRI thermometry supports the efficacy of this probe and the feedback controller in an in vivo hyperthermia treatment of canine prostate.

Acoustics↗

Temperature and SAR measurements in deep-body hyperthermia with thermocouple thermometry.

Multisensor (7-14) thermocouple thermometry is used at our department for temperature measurement with our 'Coaxial TEM' regional hyperthermia system. A special design of the thermometry system with high resolution (0.005 degrees C) and fast data-acquisition (all channels within 320 ms) together with a pulsed power technique allows assessment of specific absorption rate (SAR) information in patients along catheter tracks. A disadvantage of thermocouple thermometry, EM interference, is almost entirely eliminated by application of absorbing ferrite beads around the probe leads. We investigated the effect of remaining disturbance on the temperature decay after power-off, both experimentally in phantoms and in the clinic, and with numerical simulations. Probe and tissue characteristics influence the response time tau dist of the decay of the disturbance. In our clinical practice a normal pulse sequence is 50 s power-on, 10 s power-off: a response time longer than the power-off time results in a deflection of the temperature course at the start. Based on analysis of temperature decays correction of temperature is possible. A double-pulse technique is introduced to provide an initial correction of temperature, and fast information about accuracy. Sometimes disturbance with a relatively long response time occurs, probably due to a bad contact between probe, catheter and/or tissue. Thermocouple thermometry proved to be suitable to measure the SAR along a catheter track. This is used to optimize the SAR distribution by patient positioning before treatment. A clinical example illustrates this.

Body Temperature↗

Guidelines for thermometry in clinical hyperthermia.

High quality thermometry is needed in hyperthermia to (1) ensure safe delivery of adequate therapy and (2) provide the quantitative information needed to develop prognostic parameters which will aid research into planning and dosimetry. Currently, only invasive thermometry which is subject to several sources of artifact is available to address these requirements. This paper summarizes techniques which have been developed to reduce these artifacts to acceptable levels, outlines quality assurance requirements ensuring good practice in the use of invasive thermometry during clinical treatments and ends with a brief discussion of thermometry requirements for control of various hyperthermia systems.

Electromagnetic Fields↗