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Thermal contribution of compact bone to intervening tissue-like media exposed to planar ultrasound.

The presence of bone in the ultrasound beam path raises concerns, both in diagnostic and therapeutic applications, because significant temperature elevations may be induced at nearby soft tissue-bone interfaces due the facts that ultrasound is (i) highly absorbed in bone and (ii) reflected at soft tissue-bone interfaces in various degrees depending on angle of incidence. Consequently, in ultrasonic thermal therapy, the presence of bone in the ultrasound beam path is considered a major disadvantage and it is usually avoided. However, based on clinical experience and previous theoretical studies, we hypothesized that the presence of bone in superficial unfocused ultrasound hyperthermia can actually be exploited to induce more uniform and enhanced (with respect to the no-bone situation) temperature distributions in superficial target volumes. In particular, we hypothesize that the presence of underlying bone in superficial target volume enhances temperature elevation not only by additional direct power deposition from acoustic reflection, but also from thermal diffusion from the underlying bone. Here we report laboratory results that corroborate previous computational studies and strengthen the above-stated hypothesis. Three different temperature measurement techniques, namely, thermometric (using fibre-optic temperature probes), thermographic (using an infrared camera) and magnetic resonance imaging (using proton resonance frequency shifts), were used in high-power short-exposure, and in low-power extended-exposure, experiments using a 19 mm diameter planar transducer operating at 1.0 and 3.3 MHz (frequencies of clinical relevance). The measurements were performed on three technique-specific phantoms (with and without bone inclusions) and experimental set-ups that resembled possible superficial ultrasound hyperthermia clinical situations. Results from all three techniques were in general agreement and clearly showed that significantly higher heating rates (greater than fourfold) were induced in soft tissue-like phantom materials adjacent (within approximately 5 mm) to a bovine bone as compared to similar experiments without bone inclusions. For low-power long-exposure experiments, where thermal conduction effects are significant, the thermal impact of bone reached at distances > 10 mm from the bone surface (upstream of the bone). Therefore, we hypothesize that underlying bone exposed to planar ultrasound hyperthermia creates a high-temperature thermal boundary at depth that compensates for beam attenuation, thus producing more uniform temperature distribution in the intervening tissue layers. With appropriate technology, this finding may lead to improved thermal doses in superficial treatment sites such as the chest wall and the head/neck.

Animals↗

Aperture size to therapeutic volume relation for a multielement ultrasound system: determination of applicator adequacy for superficial hyperthermia.

Three-dimensional acoustic and thermal models were developed to simulate superficial hyperthermia treatments using a new multielement planar ultrasonic system. Typical power density and steady-state temperature distributions are presented. A parametric study was performed to determine the relationship between therapeutic volume (volume at and above 42 degrees C) and aperture size (number of active elements). The parameters investigated were: maximum allowable temperature, skin surface temperature, blood perfusion (thermal diffusion length), acoustic absorption, and frequency. Results showed that this device produces well distributed sound beams with lateral dimensions comparable to the aperture size. These simulated results were in agreement with experimental measurements. The simulated temperature distributions were uniform at each depth across the applicator's aperture. The main heating characteristics found were: (1) the therapeutic volume was directly proportional to the aperture size; (2) the lateral dimensions of the therapeutic volume were independent of the parameters studied and remained practically constant with depth for several centimeters, with a very rapid increase near the skin surface and a very rapid fall off at depth; and (3) therapeutic penetration was strongly dependent on maximum allowable temperature, frequency, and acoustic absorption; and weakly dependent on blood perfusion and skin surface temperature. These heating characteristics are new in commercial systems for superficial hyperthermia. Despite the well-distributed beams, it was found that in order to produce adequate hyperthermia with this device the lateral dimensions of tumors must be smaller than the applicator's active aperture and that thermal depth coverage must be monitored during treatments. Guidelines for aperture selection and thermometry strategies are discussed.

Acoustics↗

Diffusion in two-temperature thermal plasmas.

Combined diffusion coefficients, which allow species to be grouped into their parent gases, are derived in a thermal plasma in which the kinetic temperature of the electrons is different from that of the heavy species. As in previous calculations of combined diffusion coefficients for a one-temperature plasma, chemical equilibrium is assumed, and a plasma in a mixture of two homonuclear nonreacting gases is treated. Expressions for ambipolar diffusion in a two-temperature plasma are derived. Coupling between the electrons and the heavy species is retained in the calculations. It is confirmed that the values of the diffusion coefficients are consistent with mass conservation, in contrast to previous calculations that were based on a theory in which the electrons and heavy species were decoupled. Illustrative results are presented for a thermal plasma in different mixtures of argon and hydrogen at 1 bar, for temperatures up to 25 000 K and different ratios of electron to heavy species temperature.

Journal Article↗

Use of heating rate and specific absorption rate in the hyperthermia clinic.

The specific absorption rate (SAR), which is the mass-normalized rate of energy absorption by a biological body, has been used by hyperthermia researchers to characterize energy deposition and heating patterns in tissues and in biological models. Before thermal diffusion and blood flow alter the temperature distribution, energy deposition and heating rate (HR) are related by constants. Therefore SAR is usually calculated from the initial rate of temperature rise measured during heating. SAR is an appropriate parameter for theoretical calculations or electric field measurement in tissue. However, the ultimate parameter in hyperthermia is temperature. Instead of computing the temperature rise from SAR (W/kg) and specific heat (kcal/kg.degree C) which were originally obtained from temperature measurements, it is simpler and more convenient to use HR (degree C/W-min) directly, especially when heterogeneous tissues are involved. The advantages of using HR instead of SAR in hyperthermia clinics are discussed.

Body Temperature↗

The radicular dentine temperature during laser irradiation: a numerical modeling.

The boundary element method is well adjusted to the numerical resolution of thermal diffusion problems existing in complex volumes such as teeth. This technique is used to determine the temperatures in the bulk and on the surface of a tooth illuminated by a CO2 laser beam. The parameters taken into account in calculations include power absorbed by the tooth, laser irradiation time, and diameter of the beam on the tooth. In each case, a very fast and short heating period is observed on the tooth surface; then, the temperature decreases slowly. Inside the tooth, temperature variations are small or nonexistent. Temperature increases due to a laser beam remain concentrated at the impact region. Results are in reasonable agreement with experimental results.

Body Temperature↗

Instant myocardial blood flow monitor: its calibration and assessment of flow capacity of the intracoronary shunt tube.

BACKGROUND: We developed a new instant regional myocardial blood flow (RMBF) monitor utilizing the thermal diffusion method in which the RMBF value is presented as the value inversely proportional to the thermocouple voltage output (1/V). The purposes of this study were (1) to validate the accuracy of RMBF measurement by the instant RMBF monitor in comparison with the colored microsphere method for calibration; (2) to investigate influences of it on the RMBF; and (3) to assess changes in RMBF caused by the shunt tube insertion. METHODS: Twenty pigs were used for this study: 4 for comparison between the instant RMBF meter and the colored microsphere method, 4 for validation of reproducibility, and 6 for measurement of RMBF during shunt tube. RESULTS: The relation between RMBF values obtained by the colored microsphere method and 1/V values by instant RMBF monitor was colored microsphere = 140,992 (1/V)--231 in epicardial layer (R2 = 0.819) and colored microsphere = 111,381 (1/V)--165 in endocardial layer (R2 = 0.693). The correlation coefficient and R2 values between RMBF values measured by both methods were 0.985 and 0.839 in epicardial layer, and 0.963 and 0.679 in endocardial layer, respectively. The RMBF at each layer did not change after the attachment of the monitor. Fifteen minutes after shunt tube insertion, RMBF measured by the colored microsphere method decreased to 31.1% (p = 0.0001) and 33.7% (p = 0.0001) in epicardium and endocardium, respectively, and no difference was observed from the value measured by the instant RMBF monitor. CONCLUSIONS: This instant RMBF monitor can provide instantaneous and continuous information of RMBF without requiring tissue examination.

Animals↗

Assessment of hepatic perfusion in pigs by pharmacokinetic analysis of dynamic MR images.

The purpose of this study was to evaluate a new method based on magnetic resonance imaging for the characterization of hepatic perfusion. In nine pigs dynamic MRI was performed before and after partial occlusion of the portal vein. The pharmacokinetic analysis of the contrast enhancement resulted in a set of parameters (amplitude, A; perfusion rate, kp; elimination rate, kappa(e1); lag time, t(lag)) of which kp was expected to correlate with hepatic perfusion. Reference measurements were done with ultrasound flow-meters and with a thermal diffusion probe (TDP). MR perfusion rate kp significantly dropped under partial portal vein occlusion from an average of 11.3 to 4.9 min(-1) (P < 0.001), while the difference in amplitude A was not significant. The correlation between kp and the TDP measurement was r = 0.89 (P < 0.001). Pharmacokinetic analysis of MRI contrast enhancement provides a non-invasive assessment of hepatic perfusion.

Animals↗

High performance DNA sequencing, and the detection of mutations and polymorphisms, on the Clipper sequencer.

The Visible Genetics Clipper sequencer is a new platform for automated DNA sequencing which employs disposable MicroCel cassettes and 50 microm thick polyacrylamide gels. Two DNA ladders can be analyzed simultaneously in each of 16 lanes on a gel, after labeling with far-red absorbing dyes such as Cy5 and Cy5.5. This allows a simultaneous bidirectional sequencing of four templates. We have evaluated the Clipper sequencer, by cycle-sequencing of an M13 single-stranded DNA standard, and by coupled amplification and sequencing (CLIP) of reverse-transcribed human immunodeficiency virus (HIV-1) RNA standards and clinical patient samples. (i) Limitations of instrument. We have examined basic instrument parameters such as detector stability, background, digital sampling rate, and gain. With proper usage, the optical and electronic subsystems of the Clipper sequencer do not limit the data collection or sequence-determination processes. (ii) Limitations of gel performance. We have also examined the physics of DNA band separation on 50 microm thick MicroCel gels. We routinely obtain well-resolved sequence which can be base-called with 98.5% accuracy to position approximately 450 on an 11 cm gel, and to position approximately 900 on a 25 cm gel. Resolution on 5 and 11 cm gels ultimately is limited by a sharp decrease in spacing between adjacent bands, in the biased reptation separation regime. Fick's (thermal) diffusion appears to be of minor importance on 6 cm or 11 cm gels, but becomes an additional resolution-limiting factor on 25 cm gels. (iii) Limitations of enzymology. Template quality, primer nesting, choice of DNA polymerase, and choice between dye primers and dye terminators are key determinants of the ability to detect mutations and polymorphisms on the Clipper sequencer, as on other DNA sequencers. When CLIP is used with dye-labeled primers and a DNA polymerase of the F667Y, delta(5'--> 3' exo) class, we can routinely detect single-nucleotide mutations and polymorphisms over the 0.35-0.65 heterozygosity range. We present an example of detecting therapeutically relevant mutations in a clinical HIV-1 RNA isolate.

Bacteriophage M13↗

Experimental observation of light-induced solitary waves of analyte bands in capillary electrophoresis.

The phenomenon of electrophoresis in free solution has been studied theoretically down to the molecular level for decades. In addition, intermolecular photo-induced proton transfer reactions, which occur in a wide class of molecules (phenols and aminoarenes) as well as proteins (green fluorescent protein), were also studied extensively. However, the study of the effect of light-induced electrophoretic mobility changes of the analytes in electrophoresis was begun only recently. In the present work, capillary zone electrophoresis was chosen as the environment to measure the magnitude of these electrophoretic mobility shifts induced by light. Background electrolytes (running electrolytes) with high refractive indices were developed, allowing the capillary to work like an optical fiber. The experimental conditions for obtaining stable coupling and guided laser light along the liquid core are discussed. Experimental evidence of band compression is observed, leading to a solitary wave behavior of the analyte band (2-naphthol). These solitary waves result from competition between thermal diffusion (dispersion mechanism) and a nonlinear (band compression) effect due to the combined electrophoresis phenomenon and absorption of guided light by the molecules of the band (which are subjected to a "reversible intermolecular proton transfer reaction" as one of their decay routes). The possibilities of applying this effect to different methods and techniques are also discussed.

Buffers↗

Separating DNA sequencing fragments without a sieving matrix.

The possibility of separating appropriately labeled DNA fragments using free-flow capillary electrophoresis was predicted a few years ago based on simple theoretical arguments. Free-flow separation of double-stranded DNA (dsDNA) fragments in the 100-1000 base range was later demonstrated using a streptavidin label. In this article, we now report that end-labeled free-flow electrophoresis (ELFSE) can also be used to sequence single-stranded DNA (ssDNA). The first 100 bases of a DNA sequencing reaction were read without any sieving matrix when fractionated streptavidin was added to the 5'-end of the ssDNA fragments. These separations required only 18 min and did not require coated capillaries. An analysis of the results indicates that sample injection, analyte-wall interactions and thermal diffusion are the limiting factors at this time. Extrapolating from our data, we predict that several hundred bases could be sequenced in less than 30 min with the proper conditions. ELFSE thus offers an attractive potential alternative to polymer solutions for DNA sequencing in capillaries and microchips.

Buffers↗

Discrimination between peak spreading in capillary zone electrophoresis of proteins due to interaction with the capillary wall and due to protein microheterogeneity.

Our study attempts to find an approach to distinguishing between the contribution to peak spreading in capillary zone electrophoresis (CZE) due to protein microheterogeneity and that due to interaction with the capillary wall, by analyzing correlations between observed peak spreading and peak asymmetry. The peak asymmetry was measured as ln[(tm-t1)/(t2-tm)] where tm, t1, and t2 are migration times at the mode of the peak and at the intersection of the peak width at half-height with the ascending and descending limbs, respectively. Two isoforms of recombinant green fluorescent protein (GFP-1 and GFP-2, 27 kDa molecular mass), glucose-6-phosphate dehydrogenase (GPD, 104 kDa), and the naturally fluorescent protein R-phycoerythrin (PHYCO, 240 kDa) were subjected to CZE in polyacrylamide-coated fused-silica capillaries of 50 and 100 microns diameters under varying conditions of protein concentration, field strength, and the initial zone length. Under conditions such that contributions to peak spreading from axial diffusion, thermal effects, and electrophoretic dispersion are negligible, the analysis of the interrelations between peak width and peak asymmetry was found to allow a conclusion as to the cause of peak spreading in CZE of protein. It appears that the peak width of GFP-2 originates mostly in protein microheterogeneity while that of GFP-1 is due to protein-capillary wall interactions. For PHYCO, both microheterogeneity and protein-capillary wall interactions contribute to peak spreading. GPD exhibits relatively little microheterogeneity or interaction with capillary walls. Thus, its peak width appears to be mostly affected by an extracolumn source of spreading such as the initial zone length.

Electrophoresis, Capillary↗

The effect of alpha-adrenergic innervation on caudate blood flow.

A thermal diffusion probe, with cannulas for intracerebral microinfusion of drugs and an electrode to monitor electroencephalographic (EEG) activity, was used to examine the local effect of vasoactive amines in a 4 to 5 mm sphere of caudate nucleus in cats. The results demonstrated that it is possible to alter local cerebral blood flow (CBF) without causing any change in systemic blood pressure or heart rate, or in CBF and the EEG in the opposite caudate. One-microliter intracerebral injections, containing varying amounts of phenylephrine, increased local CBF in proportion to dose. The effect was blocked by intracerebral infusion of phentolamine. However, local alpha-adrenergic blockade did not inhibit vascular responses to blood pressure elevation or to metabolic influences on local blood flow.

Adrenergic Fibers↗

Comparative study of shortwave heating patterns in phantoms with polyethylene and silk partitions.

Specific absorption rate (SAR) and effective depths of heating patterns induced by a shortwave, pancake diathermy applicator in fat-muscle phantom are measured. Midplane partitions of polyethylene and silk screen with and without contact chemicals are used. Thermographically obtained SAR data show nearly the same value for silk-screen partitions with and without contact chemicals and slightly lower values with polyethylene partitions, provided that the partition midplanes are tightly pressed against each other. Thermometry data indicate that for low-power exposures the major error in thermographic measurements obtained after termination of heating is due to thermal diffusion and not evaporative cooling in the opened midplane of the phantom.

Diathermy↗

Double-level cauda equina compression: an experimental study with continuous monitoring of intraneural blood flow in the porcine cauda equina.

Compression of the spinal nerve roots may occur clinically at multiple levels at the same time; however, the basic pathophysiology of multi-level compression is largely unknown. In this study, the intraneural blood flow was analyzed continuously in the uncompressed segment between two compression balloons, with a pig used as an experimental model and a thermal diffusion method. At 10 mm Hg compression, there was a 64% reduction of total blood flow in the uncompressed segment compared with pre-compression values. Total ischemia occurred at pressures 10-20 mm Hg below the mean arterial blood pressure. After two-level compression at 200 mm Hg for 10 min, there was a gradual recovery of the intraneural blood flow towards the baseline. Recovery was less rapid and less complete after 2 h of compression. Double-level compression of the cauda equina can thus induce impairment of blood flow, not only at the compression sites, but also in the intermediate nerve segments located between two compression sites, even at very low pressures. These findings may have clinical importance in the understanding of the pathophysiology of multiple-level cauda equina compression.

Animals↗

Comparison of Er:YAG and 9.6-microm TE CO(2) lasers for ablation of skull tissue.

BACKGROUND AND OBJECTIVE: Craniotomy by using a drill and saw frequently results in fragmentation of the skull plate. Lasers have the potential to remove the skull plate intact, simplifying the reconstructive surgery. STUDY DESIGN/MATERIALS AND METHODS: Transverse-excited CO(2) lasers operating at the peak absorption wavelength of bone (lambda = 9.6 microm) and with pulse durations of 5-8 microsec, approximately the thermal relaxation time in hard tissue, produced high ablation rates and minimal peripheral thermal damage. Both thick (2 mm) and thin (250 microm) bovine skull samples were perforated and the ablation rates calculated. Results were compared with Q-switched and free-running Er:YAG lasers (lambda = 2.94 microm, tau(p) = 0.5 microsec and 300 microsec). RESULTS: The CO(2) laser produced ablation rates of up to 60 and 15 microm per pulse for thin and thick sections, respectively, and perforated thin and thick sections with fluences of less than 1 J/cm(2) and 6 J/cm(2), respectively. There was no discernible thermal damage and no need for water irrigation during ablation. Pulse durations > or =20 microsec resulted in significant tissue charring, which increased with the pulse duration. Although the free-running Er:YAG laser produced ablation rates of up to 100 microm per pulse, fluences of 10 J/cm(2) and 30 J/cm(2) were required to perforate thin and thick samples, respectively, and peripheral thermal damage measured 25-40 microm. CONCLUSIONS: In summary, the novel 5- to 8-microsec pulse length of the TE CO(2) laser is long enough to avoid a marked reduction in the ablation rate due to plasma formation and short enough to avoid peripheral thermal damage through thermal diffusion during the laser pulse. Furthermore, in vivo animal studies with the TE CO(2) laser are warranted for potential clinical application in craniotomy and craniofacial procedures.

Animals↗

Effect of laser radiation on tissue during laser angioplasty.

The thermal properties of adipose and ceramic atherosclerotic plaque deposits and normal arterial vessel wall were measured in the temperature range of 25-95 degrees C. In general, the data indicate that fatty plaques exhibit the lowest thermal conductivity and thermal diffusivity of the three types, whereas calcified plaques seem to have the highest values. By using a video scanning thermograph, temperature rise was recorded in normal vessel wall and plaque during ablation of tissue. Theoretical analysis suggested that realistic modeling of laser angioplasty should account for scattering of light, water content, and ablation. This paper is a preliminary report of these results.

Arteriosclerosis↗

Effects of surface irrigation on the thermal response of tissue during laser irradiation.

Effects of surface irrigation on the thermal response of tissue during laser irradiation are investigated. In particular, influence of temperature and flow rate of the irrigation fluid on the resulting temperature distributions and coagulation depths are studied. Intraluminal Nd:YAG laser irradiation of bovine muscle is performed in vitro for a fixed value of the irrigation flow rate while the irrigation temperature is varied, and for a fixed irrigation temperature while the irrigation flow rate is kept constant. Thermocouples are used to measure the temperatures within the tissue for various irradiation and irrigation conditions. Higher temperatures and deeper coagulation depths are achieved as the temperature of the irrigation fluid is increased. For sufficiently low values of irradiance and exposure time, the use of cold irrigation is shown to prevent or delay tissue carbonization. Beyond a critical irradiance and an exposure time, use of cold irrigation does not prevent tissue carbonization. Coagulation depths and temperature distributions are not affected by a change in the flow rate of laminar irrigation. Application of stagnant irrigation, however, results in an increase in coagulation depth. Results of this study suggest that the dominating mechanism of heat transfer during application of laminar irrigation is thermal diffusion as compared to the bulk motion of the fluid.

Animals↗

Comparative mathematical analyses of freezing in lung and solid tissue.

In contrast to most organs of the body, the lung is composed 80% of air and 20% of tissue. Because freezing of the lung is fundamental to cryomicroscopy, cryopreservation, and cryosurgery, mathematical analyses of freezing in lung and solid tissue were performed to determine differences in freezing behavior resulting from differences in tissue composition. A comparison of the cooling rates of these tissues is presented. At the microscopic level ultrarapid solidification is more rapid in the subpleural region of the lung than in the same region of solid tissue. In this region, the air insulates the lung tissue and prevents transfer of heat from surrounding regions. Cooling rates on the order of 10(6) K/s can be achieved in the pleura and outermost alveolar wall because their aggregate thickness is less than 5 microns in the rat. At the macroscopic level and after steady-state freezing has occurred, one-dimensional analyses show that freezing front propagation in the lung and solid tissue differs by less than 10%. This occurs even though the lung is less conductive than solid tissue; however, by having less heat storage capacity, the thermal diffusive property of lung is similar to that of solid tissue.

Air↗