Evaluation of a Balloon Implant for Simultaneous Magnetic Nanoparticle Hyperthermia and High-Dose-Rate Brachytherapy of Brain Tumor Resection Cavities.

Previous work has reported the design of a novel thermobrachytherapy (TBT) balloon implant to deliver magnetic nanoparticle (MNP) hyperthermia and high-dose-rate (HDR) brachytherapy simultaneously after brain tumor resection, thereby maximizing their synergistic effect. This paper presents an evaluation of the robustness of the balloon device, compatibility of its heat and radiation delivery components, as well as thermal and radiation dosimetry of the TBT balloon. TBT balloon devices with 1 and 3 cm diameter were evaluated when placed in an external magnetic field with a maximal strength of 8.1 kA/m at 133 kHz. The MNP solution (nanofluid) in the balloon absorbs energy, thereby generating heat, while an HDR source travels to the center of the balloon via a catheter to deliver the radiation dose. A 3D-printed human skull model was filled with brain-tissue-equivalent gel for in-phantom heating and radiation measurements around four 3 cm balloons. For the in vivo experiments, a 1 cm diameter balloon was surgically implanted in the brains of three living pigs (40-50 kg). The durability and robustness of TBT balloon implants, as well as the compatibility of their heat and radiation delivery components, were demonstrated in laboratory studies. The presence of the nanofluid, magnetic field, and heating up to 77 °C did not affect the radiation dose significantly. Thermal mapping and 2D infrared images demonstrated spherically symmetric heating in phantom as well as in brain tissue. In vivo pig experiments showed the ability to heat well-perfused brain tissue to hyperthermic levels (≥40 °C) at a 5 mm distance from the 60 °C balloon surface.

Evaluation of intrafraction couch shifts for proton treatment delivery in head-and-neck cancer patients: Toward optimal imaging frequency.

PURPOSE: Treatment planning for head-and-neck (H&N) cancer, in particular oropharynx, nasopharynx, and paranasal sinus cases, at our center requires noncoplanar proton beams due to the complexity of the anatomy and target location. Targeting accuracy for all beams is carefully evaluated by using image guidance before delivering proton beam therapy (PBT). In this study, we analyzed couch shifts to evaluate whether imaging is required before delivering each field with different couch angles. METHODS: After the Institutional Review Board approval, a retrospective analysis was performed on data from 28 H&N patients treated with PBT. Each plan was made with two-to-three noncoplanar and two-to-three coplanar fields. Cone-beam computed tomography and orthogonal kilovoltage (kV) images were acquired for setup and before delivering each field, respectively. The Cartesian (longitudinal, vertical, and lateral) and angular (pitch and roll) shifts for each field were recorded from the treatment summary on the first two fractions and every subsequent fifth fraction. A net magnitude of the three-dimensional (3D) shift in Cartesian coordinates was calculated, and a 3D vector was created from the 6 degrees of freedom coordinates for transforming couch shifts in the system coordinate to the beam's-eye view. RESULTS: A total of 3219 Cartesian and 2146 angular shift values were recorded for 28 patients. Of the Cartesian shifts, 2069 were zero (64.3%), and 1150 (35.7%) were nonzero (range, -7 to 11 mm). Of the angular shifts, 1034 (48.2%) were zero, and 1112 (51.8%) were nonzero (range, -3.0° to 3.2°). For 17 patients, the couch shifts increased toward the end of the treatment course. We also found that patients with higher body mass index (BMI) presented increased net couch shifts (p < 0.001). With BMI < 27, all overall net shift averages were <2 mm, and overall maximum net shifts were <6 mm. CONCLUSIONS: These results confirm the need for orthogonal kV imaging before delivering each field of H&N PBT at our center, where a couch rotation is involved.

Ibuprofen molecular aggregation by direct back-face transmission steady-state fluorescence.

Direct back-face transmission steady-state fluorescence was successfully applied to the study of aggregation of ibuprofen and ibuprofenate anion in solution taking advantage of its own fluorescence. The analysis of the experimental data involves the use of the differential reabsorption model to account for re-absorption phenomenon and the closed association model to describe aggregation. The fluorescence quantum yield of ibuprofenate increases when it aggregates in the presence of sodium, but it markedly decreases when 1-butyl-3-methylimidazolium is used as counterion. The proposed methodology allows the accurate determination of the critical aggregation concentrations and the mean aggregation numbers. Results were supported by complementary techniques such as time-resolved fluorescence, 1H-NMR and small-angle neutron and X-ray scattering. The developed technique constitutes a promising strategy to characterize the aggregation of poorly fluorescent surfactants that aggregates at high concentrations and hence at high absorbance values, conditions in which the most common right-angle configuration for fluorescence acquisition is troublesome due to re-absorption.

Review of Thermal and Physiological Properties of Human Breast Tissue.

Electromagnetic thermal therapies for cancer treatment, such as microwave hyperthermia, aim to heat up a targeted tumour site to temperatures within 40 and 44 °C. Computational simulations used to investigate such heating systems employ the Pennes' bioheat equation to model the heat exchange within the tissue, which accounts for several tissue properties: density, specific heat capacity, thermal conductivity, metabolic heat generation rate, and blood perfusion rate. We present a review of these thermal and physiological properties relevant for hyperthermia treatments of breast including fibroglandular breast, fatty breast, and breast tumours. The data included in this review were obtained from both experimental measurement studies and estimated properties of human breast tissues. The latter were used in computational studies of breast thermal treatments. The measurement methods, where available, are discussed together with the estimations and approximations considered for values where measurements were unavailable. The review concludes that measurement data for the thermal and physiological properties of breast and tumour tissue are limited. Fibroglandular and fatty breast tissue properties are often approximated from those of generic muscle or fat tissue. Tumour tissue properties are mostly obtained from approximating equations or assumed to be the same as those of glandular tissue. We also present a set of reliable data, which can be used for more accurate modelling and simulation studies to better treat breast cancer using thermal therapies.

Numerical Analysis of Transcranial Magnetic Stimulation Application in Patients With Orofacial Pain.

In this paper, we monitored the accuracy of non-navigated application of repetitive Transcranial Magnetic Stimulation (rTMS) in 10 patients suffering from orofacial pain by using functional magnetic resonance (fMRI), computer modeling and numerical simulation. Through a unique process, each fMRI scan was used to define a Region of Interest (ROI) where the source of the orofacial pain was located, which was to be stimulated using rTMS. For each patient, MRI scans with a spatial resolution of 0.7 mm were converted into an anatomically accurate head model. The head model including the ROI was then co-registered with a model of the stimulation coil in an electromagnetic field numerical simulator. The accuracy of rTMS application was evaluated based on the calculations of electric field intensity distribution in the ROI. The research has yielded unique insight into ROIs (with average volume 904 mm3) in patients with orofacial pain and has also extended further possibilities of human head MRI image semi-automatic segmentation. According to the calculations performed, the average ROI volume that was stimulated by an electric field with an intensity of over 80 V/m was only 4.4%, with the maximum ROI volume being 20.5%. Furthermore, a numerical study of the impact of coil rotation and translation was performed. It demonstrated a) the optimal placement of the stimulation coil can significantly increase the volume of the stimulated ROI up to 60% and b) patients with orofacial pain would need precise coil positioning with a navigation error lower than 10 mm. Due to an acceptable proccessing time of up to 6 hours, described numerical simulation opens up new options for precise rTMS treatment planning. This planning platform together with patient-specific navigated rTMS, could lead to significant increase of treatment outcomes in patients suffering from orofacial pain.

ESHO benchmarks for computational modeling and optimization in hyperthermia therapy.

BACKGROUND: The success of cancer hyperthermia (HT) treatments is strongly dependent on the temperatures achieved in the tumor and healthy tissues as it correlates with treatment efficacy and safety, respectively. Hyperthermia treatment planning (HTP) simulations have become pivotal for treatment optimization due to the possibility for pretreatment planning, optimization and decision making, as well as real-time treatment guidance. MATERIALS AND METHODS: The same computational methods deployed in HTP are also used for in silico studies. These are of great relevance for the development of new HT devices and treatment approaches. To aid this work, 3 D patient models have been recently developed and made available for the HT community. Unfortunately, there is no consensus regarding tissue properties, simulation settings, and benchmark applicators, which significantly influence the clinical relevance of computational outcomes. RESULTS AND DISCUSSION: Herein, we propose a comprehensive set of applicator benchmarks, efficacy and safety optimization algorithms, simulation settings and clinical parameters, to establish benchmarks for method comparison and code verification, to provide guidance, and in view of the 2021 ESHO Grand Challenge (Details on the ESHO grand challenge on HTP will be provided at https://www.esho.info/). CONCLUSION: We aim to establish guidelines to promote standardization within the hyperthermia community such that novel approaches can quickly prove their benefit as quickly as possible in clinically relevant simulation scenarios. This paper is primarily focused on radiofrequency and microwave hyperthermia but, since 3 D simulation studies on heating with ultrasound are now a reality, guidance as well as a benchmark for ultrasound-based hyperthermia are also included.

Characterization of Ferromagnetic Composite Implants for Tumor Bed Hyperthermia.

Hyperthermia therapy (HT) is becoming a well-recognized method for the treatment of cancer when combined with radiation or chemotherapy. There are many ways to heat a tumor and the optimum approach depends on the treatment site. This study investigates a composite ferromagnetic surgical implant inserted in a tumor bed for the delivery of local HT. Heating of the implant is achieved by inductively coupling energy from an external magnetic field of sub-megahertz frequency. Implants are formed by mechanically filling a resected tumor bed with self-polymerizing plastic mass mixed with small ferromagnetic thermoseeds. Model implants were manufactured and then heated in a 35 cm diameter induction coil of our own design. Experimental results showed that implants were easily heated to temperatures that allow either traditional HT (39-45°C) or thermal ablation therapy (>50°C) in an external magnetic field with a frequency of 90 kHz and amplitude not exceeding 4 kA/m. These results agreed well with a numerical solution of combined electromagnetic and heat transfer equations solved using the finite element method.

Effect of hyperthermia and proton beam radiation as a novel approach in chordoma cells death and its clinical implication to treat chordoma.

PURPOSE: Chordoma is a locally aggressive tumor that most commonly affects the base of the skull/clivus, cervical, and sacral spine. Conventional radiotherapy (RT), cannot be safely increased further to improve disease control due to the risk of toxicity to the surrounding critical structures. Tumor-targeted hyperthermia (HT) combined with Proton Beam Radiation Therapy (PBRT) is known to act as a potent radiosensitizer in cancer control. In this study, we investigated whether PBRT efficacy for chordoma can be enhanced in combination with HT as a radiosensitizer. MATERIAL AND METHODS: Human chordoma cell lines, U-CH2 and Mug-chor1 were treated in vitro with HT followed by PBRT with variable doses. The colony-forming assay was performed, and dose-response was characterized by linear-quadratic model fits. HSP-70 and Brachyury (TBXT) biomarkers for chordoma aggression levels were quantified by western blot analysis. Gene microarray analysis was performed by U133 Arrays. Pathway Analysis was also performed using IPA bioinformatic software. RESULTS: Our findings in both U-CH2 and Mug-Chor1 cell lines demonstrate that hyperthermia followed by PBRT has an enhanced cell killing effect when compared with PBRT-alone (p < .01). Western blot analysis showed HT decreased the expression of Brachyury protein (p < .05), which is considered a biomarker for chordoma tumor aggression. HT with PBRT also exhibited an RT-dose-dependent decrease of Brachyury expression (p < .05). We also observed enhanced HSP-70 expression due to HT, RT, and HT + RT combined in both cell lines. Interestingly, genomic data showed 344 genes expressed by the treatment of HT + RT compared to HT (68 genes) or RT (112 genes) as individual treatment. We also identified activation of death receptor and apoptotic pathway in HT + RT treated cells. CONCLUSION: We found that Hyperthermia (HT) combined with Proton Beam Radiation (PBRT) could significantly increase chordoma cell death by activating the death receptor pathway and apoptosis which has the promise to treat metastatic chordoma.

SENSEI: Direct-Detection Results on sub-GeV Dark Matter from a New Skipper CCD.

We present the first direct-detection search for sub-GeV dark matter using a new ∼2-gram high-resistivity Skipper CCD from a dedicated fabrication batch that was optimized for dark matter searches. Using 24 days of data acquired in the MINOS cavern at the Fermi National Accelerator Laboratory, we measure the lowest rates in silicon detectors of events containing one, two, three, or four electrons, and achieve world-leading sensitivity for a large range of sub-GeV dark matter masses. Data taken with different thicknesses of the detector shield suggest a correlation between the rate of high-energy tracks and the rate of single-electron events previously classified as "dark current." We detail key characteristics of the new Skipper CCDs, which augur well for the planned construction of the ∼100-gram SENSEI experiment at SNOLAB.

Feasibility of removable balloon implant for simultaneous magnetic nanoparticle heating and HDR brachytherapy of brain tumor resection cavities.

AIM: Hyperthermia (HT) has been shown to improve clinical response to radiation therapy (RT) for cancer. Synergism is dramatically enhanced if HT and RT are combined simultaneously, but appropriate technology to apply treatments together does not exist. This study investigates the feasibility of delivering HT with RT to a 5-10mm annular rim of at-risk tissue around a tumor resection cavity using a temporary thermobrachytherapy (TBT) balloon implant. METHODS: A balloon catheter was designed to deliver radiation from High Dose Rate (HDR) brachytherapy concurrent with HT delivered by filling the balloon with magnetic nanoparticles (MNP) and immersing it in a radiofrequency magnetic field. Temperature distributions in brain around the TBT balloon were simulated with temperature dependent brain blood perfusion using numerical modeling. A magnetic induction system was constructed and used to produce rapid heating (>0.2°C/s) of MNP-filled balloons in brain tissue-equivalent phantoms by absorbing 0.5 W/ml from a 5.7 kA/m field at 133 kHz. RESULTS: Simulated treatment plans demonstrate the ability to heat at-risk tissue around a brain tumor resection cavity between 40-48°C for 2-5cm diameter balloons. Experimental thermal dosimetry verifies the expected rapid and spherically symmetric heating of brain phantom around the MNP-filled balloon at a magnetic field strength that has proven safe in previous clinical studies. CONCLUSIONS: These preclinical results demonstrate the feasibility of using a TBT balloon to deliver heat simultaneously with HDR brachytherapy to tumor bed around a brain tumor resection cavity, with significantly improved uniformity of heating over previous multi-catheter interstitial approaches. Considered along with results of previous clinical thermobrachytherapy trials, this new capability is expected to improve both survival and quality of life in patients with glioblastoma multiforme.

Assessment of 53Mn deposition on Earth via accelerator mass spectrometry.

The 53Mn flux onto Earth is a quantity relevant for different extraterrestrial and astrophysical questions. It is a proxy for related fluxes, such as supernova-produced material or interplanetary dust particles. In this work, we performed a first attempt to assess the 53Mn flux by measuring the 53Mn/10Be isotopic ratio in a 1400 L sample of molten Antarctic snow by AMS (Accelerator Mass Spectrometry). Using the 10Be production rate in the atmosphere, an upper limit of 5.5 × 103 atoms cm-2 yr-1 was estimated for the deposition of extraterrestrial 53Mn. This result is compatible with one of the two discrepant values existing in the literature.

Analysis of clinical data to determine the minimum number of sensors required for adequate skin temperature monitoring of superficial hyperthermia treatments.

PURPOSE: Tumor response and treatment toxicity are related to minimum and maximum tissue temperatures during hyperthermia, respectively. Using a large set of clinical data, we analyzed the number of sensors required to adequately monitor skin temperature during superficial hyperthermia treatment of breast cancer patients. METHODS: Hyperthermia treatments monitored with >60 stationary temperature sensors were selected from a database of patients with recurrent breast cancer treated with re-irradiation (23 × 2 Gy) and hyperthermia using single 434 MHz applicators (effective field size 351-396 cm2). Reduced temperature monitoring schemes involved randomly selected subsets of stationary skin sensors, and another subset simulating continuous thermal mapping of the skin. Temperature differences (ΔT) between subsets and complete sets of sensors were evaluated in terms of overall minimum (Tmin) and maximum (Tmax) temperature, as well as T90 and T10. RESULTS: Eighty patients were included yielding a total of 400 hyperthermia sessions. Median ΔT was <0.01 °C for T90, its 95% confidence interval (95%CI) decreased to ≤0.5 °C when >50 sensors were used. Subsets of <10 sensors result in underestimation of Tmax up to -2.1 °C (ΔT 95%CI), which decreased to -0.5 °C when >50 sensors were used. Thermal profiles (8-21 probes) yielded a median ΔT < 0.01 °C for T90 and Tmax, with a 95%CI of -0.2 °C and 0.4 °C, respectively. The detection rate of Tmax ≥43 °C is ≥85% while using >50 stationary sensors or thermal profiles. CONCLUSIONS: Adequate coverage of the skin temperature distribution during superficial hyperthermia treatment requires the use of >50 stationary sensors per 400 cm2 applicator. Thermal mapping is a valid alternative.

Cross-sectional study to assess the association of color vision with mercury hair concentration in children from Brazilian Amazonian riverine communities.

BACKGROUND: Mercury exposure in the Brazilian Amazon region has been an important concern since the 1980s, when gold mining activities contaminated many Amazonian river basins and the fish therein. Mercury exposure in humans can lead to changes in neural function. The visual system has been used as a functional indicator of methylmercury (organic) and mercury vapour (inorganic) toxicity. Children are particularly vulnerable to this metal exposure. OBJECTIVE: To compare the color vision of children from riverine communities of mercury-exposed (Tapajós basin) and non-exposed Amazonian rivers (Tocantins basin). METHODS: The study sample was 176 children, aged 7-14 years old. Children from two locations in the mercury-exposed Tapajós river basin, Barreiras (n = 71) and São Luiz do Tapajos (n = 41), were compared to children from Limoeiro do Ajuru (n = 64), a non-exposed area in the Tocantins river basin. No caregiver reported that any children had contact with mercury vapour during their lifetime, and probably most of the mercury in their bodies was obtained by fish consumption. Because of this, we decided to evaluate the mercury exposure by total mercury levels in hair samples, a good marker for organic mercury, and not in the urine, a marker for inorganic mercury. Color vision was assessed by the Lanthony Desaturated D-15 test. We used the Vingrys and King-Smith method (1988) to quantify the hue ordering test. The primary visual outcomes from this analysis were C-index (magnitude of the hue ordering error) and angle of the hue ordering. RESULTS: The Tapajós children had a higher mean hair mercury level (mean: 4.5 µg/g; range: 0.26-22.38 µg/g) than that of Tocantins children (mean: 0.49 µg/g; range: 0.03-1.91 µg/g) (p < 0.05). Mean difference was approximately 4.01 µg/g with a 95% confidence interval of 2.79-5.23. The results of the Lanthony D-15d test showed no significant difference between the C-index mean values of the Tapajós and Tocantins groups (p > 0.05). There was a weak linear correlation in the average C-index obtained from both eyes and the total mercury concentration. Multiple logistic regression analysis indicated that the location of the community and the age had a greater influence on the visual outcomes than the sex of the children and within-locale variation in mercury concentration. CONCLUSION: Our results suggest a difference in one aspect of vision, that is, color vision, between children living in two different river basins in the Brazilian Amazon. The association may be related to Hg exposure but also appeared related to the location of the community and age.

Emotional and motor symptoms in riverside dwellers exposed to mercury in the Amazon. / Manifestações emocionais e motoras de ribeirinhos expostos ao mercúrio na Amazônia.

INTRODUCTION:: The investigation of clinical and neurological impactations associated with exposure to mercury levels in exposed populations is necessary in the Amazon. OBJECTIVE:: To analyze emotional and motor symptoms of riverside dwellers exposed by diet in the municipalities of Itaituba and Acará, in Pará, Brazil. METHODS:: Hair samples were collected to assess the total mercury (HgT). Demographic data as well as emotional (depression, anxiety and insomnia) and motor (paresthesia, muscle weakness, loss of balance when walking, tremors, limb pain and dysarthria) symptomatology data were obtained. RESULTS:: Mean levels of HgT in Itaituba were significantly higher (p < 0.0001) than in Acará. Emotional symptoms were identified in 26 (26.5%) participants from Itaituba and in 24 (52.2%) from Acará. Specific motor complaints in Itaituba occurred in 63 (64.3%) volunteers; the most frequently mentioned afflictions were limb pain (36.7%), paresthesia (32.6%) and muscle weakness (27.5%). In Acará, 33 (71.7%) participants had motor symptoms, the majority of which complained of paresthesia (54.3%), limb pain (52.2%) and tremors (34.8%). Average HgT levels in Itaituba in those with emotional and motor symptoms were above the tolerable levels (6 µg/g) determined by the World Health Organization. CONCLUSION:: Results showed that mercury levels in emotional and motor symptoms in Itaituba are higher than in riverside dwellers in Acará. Further studies, including the application of specific qualitative and/or quantitative standard tests, as well as the investigation of other clinical signs are necessary.

Steady-State Fluorescence of Highly Absorbing Samples in Transmission Geometry: A Simplified Quantitative Approach Considering Reabsorption Events.

A simplified methodology to acquire steady-state emission spectra and quantum yields of highly absorbing samples is presented. The experimental setup consists of a commercial spectrofluorometer adapted to transmission geometry, allowing the detection of the emitted light at 180° with respect to the excitation beam. The procedure includes two different mathematical approaches to describe and reproduce the distortions caused by reabsorption on emission spectra and quantum yields. Toluene solutions of 9,10-diphenylanthracence, DPA, with concentrations ranging between 1.12 × 10-5 and 1.30 × 10-2 M, were used to validate the proposed methodology. This dye has significant probability of reabsorption and re-emission in concentrated solutions without showing self-quenching or aggregation phenomena. The results indicate that the reabsorption corrections, applied on molecular emission spectra and quantum yields of the samples, accurately reproduce experimental data. A further discussion is performed concerning why the re-emitted radiation is not detected in the experiments, even at the highest DPA concentrations.

Focused ultrasound for treatment of bone tumours.

PURPOSE: Focused ultrasound (FUS) is a modality with rapidly expanding applications across the field of medicine. Treatment of bone lesions with FUS including both benign and malignant tumours has been an active area of investigation. Recently, as a result of a successful phase III trial, magnetic resonance-guided FUS is now a standardised option for treatment of painful bone metastases. This report reviews the clinical applications amenable to treatment with FUS and provides background on FUS and image guidance techniques, results of clinical studies, and future directions. METHODS: A comprehensive literature search and review of abstracts presented at the recently completed fourth International Focused Ultrasound Symposium was performed. Case reports and older publications revisited in more recent studies were excluded. For clinical studies that extend beyond bone tumours, only the data regarding bone tumours are presented. RESULTS: Fifteen studies assessing the use of focused ultrasound in treatment of primary benign bone tumours, primary malignant tumours, and metastatic tumours meeting the search criteria were identified. For these clinical studies the responders group varied within 91-100%, 85-87% and 64-94%, respectively. Major complications were reported in the ranges 0%, 0-28% and 0-4% for primary benign, malignant and metastatic tumours, respectively. CONCLUSIONS: Image-guided FUS is both safe and effective in the treatment of primary and secondary tumours. Additional phase III trials are warranted to more fully define the role of FUS in treatment of both benign and malignant bone tumours.

Reaction Chemistry Generated by Nanosecond Pulsed Dielectric Barrier Discharge Treatment is Responsible for the Tumor Eradication in the B16 Melanoma Mouse Model.

Melanoma is one of the most aggressive metastatic cancers with resistance to radiation and most chemotherapy agents. This study highlights an alternative treatment for melanoma based on nanosecond pulsed dielectric barrier discharge (nsP DBD). We show that a single nsP DBD treatment, directly applied to a 5 mm orthotopic mouse melanoma tumor, completely eradicates it 66% (n = 6; p ≤ 0.05) of the time. It was determined that reactive oxygen and nitrogen species produced by nsP DBD are the main cause of tumor eradication, while nsP electric field and heat generated by the discharge are not sufficient to kill the tumor. However, we do not discount that potential synergy between each plasma generated component (temperature, electric field and reactive species) can enhance the killing efficacy.

Design and optimization of an ultra wideband and compact microwave antenna for radiometric monitoring of brain temperature.

We present the modeling efforts on antenna design and frequency selection to monitor brain temperature during prolonged surgery using noninvasive microwave radiometry. A tapered log-spiral antenna design is chosen for its wideband characteristics that allow higher power collection from deep brain. Parametric analysis with the software HFSS is used to optimize antenna performance for deep brain temperature sensing. Radiometric antenna efficiency (η) is evaluated in terms of the ratio of power collected from brain to total power received by the antenna. Anatomical information extracted from several adult computed tomography scans is used to establish design parameters for constructing an accurate layered 3-D tissue phantom. This head phantom includes separate brain and scalp regions, with tissue equivalent liquids circulating at independent temperatures on either side of an intact skull. The optimized frequency band is 1.1-1.6 GHz producing an average antenna efficiency of 50.3% from a two turn log-spiral antenna. The entire sensor package is contained in a lightweight and low-profile 2.8 cm diameter by 1.5 cm high assembly that can be held in place over the skin with an electromagnetic interference shielding adhesive patch. The calculated radiometric equivalent brain temperature tracks within 0.4 °C of the measured brain phantom temperature when the brain phantom is lowered 10 °C and then returned to the original temperature (37 °C) over a 4.6-h experiment. The numerical and experimental results demonstrate that the optimized 2.5-cm log-spiral antenna is well suited for the noninvasive radiometric sensing of deep brain temperature.

Non-invasive measurement of brain temperature with microwave radiometry: demonstration in a head phantom and clinical case.

This study characterizes the sensitivity and accuracy of a non-invasive microwave radiometric thermometer intended for monitoring body core temperature directly in brain to assist rapid recovery from hypothermia such as occurs during surgical procedures. To study this approach, a human head model was constructed with separate brain and scalp regions consisting of tissue equivalent liquids circulating at independent temperatures on either side of intact skull. This test setup provided differential surface/deep tissue temperatures for quantifying sensitivity to change in brain temperature independent of scalp and surrounding environment. A single band radiometer was calibrated and tested in a multilayer model of the human head with differential scalp and brain temperature. Following calibration of a 500MHz bandwidth microwave radiometer in the head model, feasibility of clinical monitoring was assessed in a pediatric patient during a 2-hour surgery. The results of phantom testing showed that calculated radiometric equivalent brain temperature agreed within 0.4°C of measured temperature when the brain phantom was lowered 10°C and returned to original temperature (37°C), while scalp was maintained constant over a 4.6-hour experiment. The intended clinical use of this system was demonstrated by monitoring brain temperature during surgery of a pediatric patient. Over the 2-hour surgery, the radiometrically measured brain temperature tracked within 1-2°C of rectal and nasopharynx temperatures, except during rapid cooldown and heatup periods when brain temperature deviated 2-4°C from slower responding core temperature surrogates. In summary, the radiometer demonstrated long term stability, accuracy and sensitivity sufficient for clinical monitoring of deep brain temperature during surgery.

Numerical 3D modeling of heat transfer in human tissues for microwave radiometry monitoring of brown fat metabolism.

BACKGROUND: Brown adipose tissue (BAT) plays an important role in whole body metabolism and could potentially mediate weight gain and insulin sensitivity. Although some imaging techniques allow BAT detection, there are currently no viable methods for continuous acquisition of BAT energy expenditure. We present a non-invasive technique for long term monitoring of BAT metabolism using microwave radiometry. METHODS: A multilayer 3D computational model was created in HFSS™ with 1.5 mm skin, 3-10 mm subcutaneous fat, 200 mm muscle and a BAT region (2-6 cm3) located between fat and muscle. Based on this model, a log-spiral antenna was designed and optimized to maximize reception of thermal emissions from the target (BAT). The power absorption patterns calculated in HFSS™ were combined with simulated thermal distributions computed in COMSOL® to predict radiometric signal measured from an ultra-low-noise microwave radiometer. The power received by the antenna was characterized as a function of different levels of BAT metabolism under cold and noradrenergic stimulation. RESULTS: The optimized frequency band was 1.5-2.2 GHz, with averaged antenna efficiency of 19%. The simulated power received by the radiometric antenna increased 2-9 mdBm (noradrenergic stimulus) and 4-15 mdBm (cold stimulus) corresponding to increased 15-fold BAT metabolism. CONCLUSIONS: Results demonstrated the ability to detect thermal radiation from small volumes (2-6 cm3) of BAT located up to 12 mm deep and to monitor small changes (0.5 °C) in BAT metabolism. As such, the developed miniature radiometric antenna sensor appears suitable for non-invasive long term monitoring of BAT metabolism.