Dynamic Chemical Shift Imaging for Image-Guided Thermal Therapy

Magnetic resonance temperature imaging (MRTI) is recognized as a noninvasive means to provide temperature imaging for guidance in thermal therapies. The most common method of estimating temperature changes in the body using MR is by measuring the water proton resonant frequency (PRF) shift. Calculation of the complex phase difference (CPD) is the method of choice for measuring the PRF indirectly since it facilitates temperature mapping with high spatiotemporal resolution. Chemical shift imaging (CSI) techniques can provide the PRF directly with high sensitivity to temperature changes while minimizing artifacts commonly seen in CPD techniques. However, CSI techniques are currently limited by poor spatiotemporal resolution. This research intends to develop and validate a CSI-based MRTI technique with intentional spectral undersampling which allows relaxed parameters to improve spatiotemporal resolution. An algorithm based on autoregressive moving average (ARMA) modeling is developed and validated to help overcome limitations of Fourier-based analysis allowing highly accurate and precise PRF estimates. From the determined acquisition parameters and ARMA modeling, robust maps of temperature using the k-means algorithm are generated and validated in laser treatments in ex vivo tissue. The use of non-PRF based measurements provided by the technique is also investigated to aid in the validation of thermal damage predicted by an Arrhenius rate dose model.

Fast magnetic resonance temperature imaging for focused ultrasound thermal therapy

The current standard for temperature sensitive imaging using magnetic resonance (MR) is 2-D, spoiled, fast gradient-echo (fGRE) phase-difference imaging exploiting temperature dependent changes in the proton resonance frequency (PRF). The echo-time (TE) for optimal sensitivity is larger than the typical repetition time (TR) of an fGRE sequence. Since TE must be less than TR in the fGRE sequence, this limits the technique's achievable sensitivity, spatial, and temporal resolution. This adversely affects both accuracy and volume coverage of the measurements. Accurate measurement of the rapid temperature changes associated with pulsed thermal therapies, such as high-intensity focused ultrasound (FUS), at optimal temperature sensitivity requires faster acquisition times than those currently available. ^ Use of fast MR acquisition strategies, such as interleaved echo-planar and spiral imaging, can provide the necessary increase in temporal performance and sensitivity while maintaining adequate signal-to-noise and in-plane spatial resolution. This research explored the adaptation and optimization of several fast MR acquisition methods for thermal monitoring of pulsed FUS thermal therapy. Temperature sensitivity, phase-difference noise and phase-difference to phase-difference-to noise ratio for the different pulse sequences were evaluated under varying imaging parameters in an agar gel phantom to establish optimal sequence parameters for temperature monitoring. The temperature sensitivity coefficient of the gel phantom was measured, allowing quantitative temperature extrapolations. ^ Optimized fast sequences were compared based on the ability to accurately monitor temperature changes at the focus of a high-intensity focused ultrasound unit, volume coverage, and contrast-to-noise ratio in the temperature maps. Operating parameters, which minimize complex phase-difference measurement errors introduced by use of the fast-imaging methods, were established. ^

Determination of the Most Efficient Temperature for Radiofrequency Ablation of Renal Cells: A Prospective Study in Dogs

Background and Purpose: Radiofrequency (RF) ablation of renal tumors is a major technique for tumor cell destruction while preserving healthy renal parenchyma. There is no consensus in the literature regarding the optimal temperature, impedance, and time for RF application for effective cell destruction. This study investigated two variables while keeping time unchanged: Temperature for RF cell destruction and tissue impedance in dog kidneys. Materials and Methods: Sixteen dogs had renal punctures through videolaparoscopy for RF interstitial tissue ablation. A RF generator was applied for 10 minutes to the dog's kidney at different target temperatures: 80 degrees C, 90 degrees C, and 100 degrees C. On postoperative day14, the animals were sacrificed and nephrectomized. All lesions were macroscopically and microscopically examined. The bioelectrical impedance was evaluated at three different temperatures. Results: Renal injuries were wider and deeper at 90 degrees C (P < 0.001), and they were similar at 80 degrees C and 100 degrees C. The bioelectrical impedance was lower at 90 degrees C than at the temperatures of 80 degrees C and 100 degrees C (P < 0.001). Viable cells in the RF ablation tissue area were not found in the microscopic examination. Conclusion: The most effective cell destruction in terms of width and depth was achieved at 90 degrees C, which was also the optimal temperature for tissue impedance. RF ablation of renal cells eliminated all viable cells.

Magnetic and in vitro heating properties of implants formed in situ from injectable formulations and containing superparamagnetic iron oxide nanoparticles (SPIONs) embedded in silica microparticles for magnetically induced local hyperthermia

The biological and therapeutic responses to hyperthermia, when it is envisaged as an anti-tumor treatment modality, are complex and variable. Heat delivery plays a critical role and is counteracted by more or less efficient body cooling, which is largely mediated by blood flow. In the case of magnetically mediated modality, the delivery of the magnetic particles, most often superparamagnetic iron oxide nanoparticles (SPIONs), is also critically involved. We focus here on the magnetic characterization of two injectable formulations able to gel in situ and entrap silica microparticles embedding SPIONs. These formulations have previously shown suitable syringeability and intratumoral distribution in vivo. The first formulation is based on alginate, and the second on a poly(ethylene-co-vinyl alcohol) (EVAL). Here we investigated the magnetic properties and heating capacities in an alternating magnetic field (141 kHz, 12 mT) for implants with increasing concentrations of magnetic microparticles. We found that the magnetic properties of the magnetic microparticles were preserved using the formulation and in the wet implant at 37 degrees C, as in vivo. Using two orthogonal methods, a common SLP (20 Wg(-1)) was found after weighting by magnetic microparticle fraction, suggesting that both formulations are able to properly carry the magnetic microparticles in situ while preserving their magnetic properties and heating capacities. (C) 2010 Elsevier B.V. All rights reserved.

Fontes hidrominerais do Brasil: componentes biologicamente ativos (BAC) naturais

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

The Thermal Effects of Therapeutic Lasers with 810 and 904 nm Wavelengths on Human Skin

Objective: To investigate the effect of therapeutic infrared class 3B laser irradiation on skin temperature in healthy participants of differing skin color, age, and gender. Background: Little is known about the potential thermal effects of Low Level Laser Therapy (LLLT) irradiation on human skin. Methods: Skin temperature was measured in 40 healthy volunteers with a thermographic camera at laser irradiated and control (non-irradiated) areas on the skin. Six irradiation doses (2-12 J) were delivered from a 200mW, 810nm laser and a 60mW, 904nm laser, respectively. Results: Thermal effects of therapeutic LLLT using doses recommended in the World Association for Laser Therapy (WALT) guidelines were insignificant; below 1.5 degrees C in light, medium, and dark skin. When higher irradiation doses were used, the 60mW, 904 nm laser produced significantly (p < 0.01) higher temperatures in dark skin (5.7, SD +/- 1.8 degrees C at 12 J) than in light skin, although no participants requested termination of LLLT. However, irradiation with a 200mW, 810nm laser induced three to six times more heat in dark skin than in the other skin color groups. Eight of 13 participants with dark skin asked for LLLT to be stopped because of uncomfortable heating. The maximal increase in skin temperature was 22.3 degrees C. Conclusions: The thermal effects of LLLT at doses recommended by WALT-guidelines for musculoskeletal and inflammatory conditions are negligible (< 1.5 degrees C) in light, medium, and dark skin. However, higher LLLT doses delivered with a strong 3B laser (200mW) are capable of increasing skin temperature significantly and these photothermal effects may exceed the thermal pain threshold for humans with dark skin color.

An investigation of the interrelationship between manipulative therapy-induced hypoalgesia and sympathoexcitation

Objective: To investigate a proposed model in which manipulative therapy produces a treatment-specific initial hypoalgesic and sympathoexcitatory effect by activating a descending pain inhibitory system. The a priori hypothesis tested was that manipulative therapy produces mechanical hypoalgesia and sympatho-excitation beyond that produced by placebo or control. Furthermore, these effects would be correlated, thus supporting the proposed model. Design: A randomized, double-blind, placebo-controlled, repeated-measures study of the initial effect of treatment. Setting: Clinical neurophysiology laboratory. Subjects: Twenty-four subjects (13 women and 11 men; mean age, 49 yr) with chronic lateral epicondylalgia (average duration, 6.2 months). Intervention: Cervical spine lateral glide oscillatory manipulation, placebo and control. Outcome Measures: Pressure pain threshold, thermal pain threshold, pain-free grip strength test, upper limb tension test 2b, skin conductance, pileous and glabrous skin temperature and blood flux. Results: Treatment produced hypoalgesic and sympathoexcitatory changes significantly grater than those of placebo and control (p < .03). Confirmatory factor-analysis modeling, which was performed on the pain-related measures and the indicators of sympathetic nervous system function, demonstrated a significant correlation (r = .82) between the latencies of manipulation-induced hypoalgesia and sympathoexcitation. The Lagrange Multiplier test and Wald test indicated that the two latent factors parsimoniously and appropriately represented their observed variables. Conclusions: Manual therapy produces a treatment-specific initial hypoalgesic and sympathoexcitatory effect beyond that of placebo or control. The strong correlation between hypoalgesic and sympathoexcitatory effects suggests that a central control mechanism might be activated by manipulative therapy.

Naloxone fails to antagonize initial hypoalgesic effect of a manual therapy treatment for lateral epicondylalgia

Background: Recent research has shown that Mulligan's Mobilization With Movement treatment technique for the elbow (MWM), a peripheral joint mobilization technique, produces a substantial and immediate pain relief in chronic lateral epicondylalgia (48% increase in pain-free grip strength).(1) This hypoalgesic effect is far greater than that previously reported with spinal manual therapy treatments, prompting speculation that peripheral manual therapy treatments may differ in mechanism of action to spinal manual therapy techniques. Naloxone antagonism and tolerance studies, which employ widely accepted tests for the identification of endogenous opioid-mediated pain control mechanisms, have shown that spinal manual therapy-induced hypoalgesia does not involve an opioid mechanism. Objective: The aim of this study was to evaluate the effect of naloxone administration on the hypoalgesic effect of MWM. Methods: A randomized, controlled trial evaluated the effect of administering naloxone, saline, or no-substance control injection on the MWM-induced hypoalgesia in 18 participants with lateral epicondylalgia. Pain-free grip strength, pressure pain threshold, thermal pain threshold, and upper limb neural tissue provocation test 2b were the outcome measures. Results: The results demonstrated that the initial hypoalgesic effect of the MWM was not antagonized by naloxone, suggesting a nonopioid mechanism of action. Conclusions: The studied peripheral mobilization treatment technique appears to have a similar effect profile to previously studied spinal manual therapy techniques, suggesting a nonopioid-mediated hypoalgesia following manual therapy.

Target-specific multiphysics modeling for thermal medicine applications

Dissertation to obtain the degree of Doctor of Philosophy in Biomedical Engineering

Histological analyses of thermal effect caused by 1.2 W diode laser irradiation at rat periodontal pockets

The aim of this in vivo study was to evaluate the thermal effects caused by 810 nm 1.2 W diode laser irradiation of periodontal tissues. Despite all data available concerning the laser application for periodontal treatment, one of the most relevant challenges is to prevent the harmful tissue heating induced by different clinical protocols. Periodontal pockets were induced at molars in 96 rats. Several irradiation powers under CW mode were investigated: 0, 400, 600, 800, 1000, 1200 mW. The pockets were irradiated using a 300 A mu m frontal illumination fiber. The animals were killed at 4 or 10 days after irradiation. The mandible was surgically removed and histologically processed. The histological sections stained with H/E demonstrated that irradiation parameters up to 1000 mW were thermally safe for the periodontal tissues. The sections stained with Brown & Brenn technique evidenced bacteria in the periodontal tissues. Consequently, the diode laser irradiation as a unique treatment was not capable to eliminate bacteria of the biofilm present in the pockets. According to the methodology used here, it was concluded that the thermal variation promoted by a diode laser can cause damage to periodontal tissues depending on the energy density used. The 1.2 W diode laser irradiation itself does not control the bacteria present in the biofilm of the periodontal pockets without mechanical action. The knowledge of proper high intensity laser parameters and methods of irradiation for periodontal protocols may prevent any undesirable thermal damage to the tissues.

Effect of Er : YAG and diode laser irradiation on the root surface: Morphological and thermal analysis

Background: the aim of the present study was to compare the effects of Er:YAG and diode laser treatments of the root surface on intrapulpal temperature after scaling and root planing with hand instruments.Methods: Fifteen extracted single-rooted teeth were scaled and root planed with hand instruments. The teeth were divided into 3 groups of 5 each and irradiated on their buccal and lingual surfaces: group A: Er:YAG laser, 2.94 mum/100 mJ/10 Hz/ 30 seconds; group B: diode laser, 810 nm/1.0 W/0.05 ms/30 seconds; group C: diode laser, 810 nm/1.4 W/0.05 ms/30 seconds. The temperature was monitored by means of a type T thermocouple (copper-constantan) positioned in the pulp chamber to assess pulpal temperature during and before irradiation. Afterwards, the specimens were longitudinally sectioned, and the buccal and lingual surfaces of each root were analyzed by scanning electron microscopy.Results: In the Er:YAG laser group, the thermal analysis revealed an average temperature of -2.2 +/- 1.5degreesC, while in the diode laser groups, temperatures were 1.6 +/- 0.8degreesC at 1.0 W and 3.3 +/- 1.0degreesC at 1.4 W. Electronic micrographs revealed that there were no significant morphological changes, such as charring, melting, or fusion, in any group, although the specimens were found to be more irregular in the Er:YAG laser group.Conclusions: the application of Er:YAG and diode lasers at the utilized parameters did not induce high pulpal temperatures. Root surface irregularities were more pronounced after irradiation with an Er:YAG laser than with a diode laser.

Toxicity of photodynamic therapy with LED associated to Photogem (R): An in vivo study

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Clinical evaluation of low-level laser therapy and fluoride varnish for treating cervical dentinal hypersensitivity

The aim of this study was to evaluate in vivo the use of low-level galium-aluminium-arsenide (GaAlAs) (BDP 600) laser and sodium fluoride varnish (Duraphat((R))) in the treatment of cervical dentine hypersensitivity. Twelve patients, with at least two sensitive teeth were selected. A total of 60 teeth were included in the trial. Prior to desensitizing treatment, dentine hypersensitivity was assessed by a thermal stimulus and patients' response to the examination was considered to be a control. The GaAlAs laser (15 mW, 4 J/cm(2)) was irradiated on contact mode and fluoride varnish was applied at cervical region. The efficiency of the treatments was assessed at three examination periods: immediately after first application, 15 and 30 days after the first application. The degree of sensitivity was determined following predefined criteria. Data were submitted to analysis and no statistically significant difference was observed between fluoride varnish and laser. Considering the treatments separately, there was no significant difference for the fluoride varnish at the three examination periods, and for laser therapy, significant difference (P < 0.05) was found solely between the values obtained before the treatment and 30 days after the first application. It may be concluded that both treatments may be effective in decreasing cervical dentinal hypersensitivity. Moreover, the low-level GaAlAs laser showed improved results for treating teeth with higher degree of sensitivity.

Toxicity of photodynamic therapy with LED associated to Photogem (R): An in vivo study

The aims of this study were to evaluate the effects of PhotogemA (R)-mediated photosensitization on rat palatal mucosa and the biodistribution of the photosensitizer in this tissue. A solution of PhotogemA (R) (500 or 1000 mg/l) was applied to the palatal mucosa for 30 min and the exposure time to blue LED (460 nm) was 20 min (144 J/cm(2)). At 0, 1, 3, and 7 days, palatal mucosa was photographed for macroscopic analysis. After killing, the palate was removed for microscopic analysis. Thermal mapping evaluated temperature change in the tissue during irradiation. All experimental groups revealed intact mucosa in the macroscopic analysis. Tissue alterations were observed microscopically for only four out of 80 animals subjected to PDT. Fluorescence emitted by PhotogemA (R) was identified and was limited to the epithelial layer. A temperature increase from 35 to 41A degrees C was recorded. PhotogemA (R)- mediated PDT was not toxic to the rat palatal mucosa.