Real-time non-invasive control of ultrasound hyperthermia using high-frequency ultrasonic backscattered energy inex vivotissue andin vivoanimal studies.

Objective.A reliable, calibrated, non-invasive thermometry method is essential for thermal therapies to monitor and control the treatment. Ultrasound (US) is an effective thermometry modality due to its relatively high sensitivity to temperature changes, and fast data acquisition and processing capabilities.Approach.In this work, the change in backscattered energy (CBE) was used to control the tissue temperature non-invasively using a real-time proportional-integral-derivative (PID) controller. A clinical high-frequency US scanner was used to acquire radio-frequency echo data fromex vivoporcine tissue samples andin vivomice hind leg tissue while the tissue was treated with mild hyperthermia by a focused US applicator. The PID controller maintained the focal temperature at approximately 40 °C for about 4 min.Main results.The results show that the US thermometry based on CBE estimated by a high-frequency US scanner can produce 2D temperature maps of a localized heating region and to estimate the focal temperature during mild hyperthermia treatments. The CBE estimated temperature varied by an average of ±0.85 °C and ±0.97 °C, compared to a calibrated thermocouple, inex vivoandin vivostudies, respectively. The mean absolute deviations of CBE thermometry during the controlled hyperthermia treatment were ±0.45 °C and ±0.54 °C inex vivoandin vivo,respectively.Significance.It is concluded that non-invasive US thermometry via backscattered energies at high frequencies can be used for real-time monitoring and control of hyperthermia treatments with acceptable accuracy. This provides a foundation for an US mediated drug delivery system.

Toward Upconversion (Yb-Er) and near-Infrared (Yb-Ho-Er, Nd-Yb) Thermometry with Sea Urchin Type GdPO4 Nanoarchitectures.

In recent years, optical temperature probes operating in the second near-infrared (BW-II) and third near-infrared (BW-III) biological windows have garnered significant attention in the scientific community. For biological applications these probes offer distinct advantages, including enhanced tissue penetration depth, minimal autofluorescence, and a remarkable improvement in imaging sensitivity and spatial resolution. Moving toward theranostic applications, there is a growing demand for the development of materials that integrate both BW-II and BW-III thermometry systems with drug delivery functionalities. In this study, we concentrate on the development of GdPO4 materials, utilizing both hard and sacrificial template routes to synthesize (hollow) GdPO4 porous sea urchin-like particles. We first investigated the development of a Boltzmann-type thermometer utilizing an Yb-Er upconversion system, designed to operate within the physiological temperature range. Our exploration extends to the potential of GdPO4 particles in near-infrared (NIR) thermometry, spanning the first, second, and third biological windows with systems like Yb-Ho-Er, Nd-Yb, and Ho-Yb, respectively. We further examined the temperature impact of the Yb-Ho-Er system on the NIR emission within a biologically relevant setting, using a phantom that replicates biological tissue. Furthermore, we illustrate the successful loading of these materials with doxorubicin (DOX·HCl), a model anticancer drug, showing these particles exhibit pH-dependent DOX release. This demonstrates the versatility of these materials as upconversion and NIR thermometers while simultaneously serving as an on-demand drug carrier. The investigation involves assessing their cytotoxicity on specific human cells (Normal Human Dermal Fibroblasts (NHDFs)), to determine their viability for potential use in biological applications. The study also investigates how effectively loading the particles with DOX enables targeted delivery to a cellular model of lymphoma (Jurkat E6-1), resulting in cell death. This comprehensive analysis highlights the promising potential of GdPO4 particles for medical applications.

Intravital microscopic thermometry of rat mammary epithelium by fluorescent nanodiamond.

Quantum sensing using the fluorescent nanodiamond (FND) nitrogen-vacancy center enables physical/chemical measurements of the microenvironment, although application of such measurements in living mammals poses significant challenges due to the unknown biodistribution and toxicity of FNDs, the limited penetration of visible light for quantum state manipulation/measurement, and interference from physiological motion. Here, we describe a microenvironmental thermometry technique using FNDs in rat mammary epithelium, an important model for mammary gland biology and breast cancer research. FNDs were injected directly into the mammary gland. Microscopic observation of mammary tissue sections showed that most FNDs remained in the mammary epithelium for at least 8 weeks. Pathological examination indicated no obvious change in tissue morphology, suggesting negligible toxicity. Optical excitation and detection were performed through a skin incision. Periodic movements due to respiration and heartbeat were mitigated by frequency filtering of the signal. Based on these methods, we successfully detected temperature elevation in the mammary epithelium associated with lipopolysaccharide-induced inflammation, demonstrating the sensitivity and relevance of the technique in biological contexts. This study lays the groundwork for expanding the applicability of quantum sensing in biomedical research, providing a tool for real-time monitoring of physiological and pathological processes.

Cellular Thermal Biology Using Fluorescent Nanothermometers.

It has been known that cells have mechanisms to sense and respond to environmental noxiousness and mild temperature changes, such as heat shock response and thermosensitive TRP channels. Meanwhile, new methods of measuring temperature at the cellular level has recently been developed using fluorescent nanothermometers. Among these thermometers, fluorescent polymeric thermometers and fluorescent nanodiamonds excel in the properties required for intracellular thermometry. By using these novel methods to measure the temperature of single cells in cultures and tissues, it was revealed that spontaneous spatiotemporal temperature fluctuations occur within cells. Furthermore, the temperature fluctuations were related to organelles such as mitochondria and cellular and physiological functions, revealing a close relationship between intracellular temperature and cellular functions.

Evaluation of magnetic resonance thermometry performance during MR-guided hyperthermia treatment of soft-tissue sarcomas in the lower extremities and pelvis.

INTRODUCTION: This study evaluated the performance of magnetic resonance thermometry (MRT) during deep-regional hyperthermia (HT) in pelvic and lower-extremity soft-tissue sarcomas. MATERIALS AND METHODS: 17 pelvic (45 treatments) and 16 lower-extremity (42 treatments) patients underwent standard regional HT and chemotherapy. Pairs of double-echo gradient-echo scans were acquired during the MR protocol 1.4 s apart. For each pair, precision was quantified using phase data from both echoes ('dual-echo') or only one ('single-echo') in- or excluding body fat pixels in the field drift correction region of interest. The precision of each method was compared to that of the MRT approach using a built-in clinical software tool (SigmaVision). Accuracy was assessed in three lower-extremity patients (six treatments) using interstitial temperature probes. The Jaccard coefficient quantified pretreatment motion; receiver operating characteristic analysis assessed its predictability for acceptable precision (<1 °C) during HT. RESULTS: Compared to the built-in dual-echo approach, single-echo thermometry improved the mean temporal precision from 1.32 ± 0.40 °C to 1.07 ± 0.34 °C (pelvis) and from 0.99 ± 0.28 °C to 0.76 ± 0.23 °C (lower extremities). With body fat-based field drift correction, single-echo mean accuracy improved from 1.4 °C to 1.0 °C. Pretreatment bulk motion provided excellent precision prediction with an area under the curve of 0.80-0.86 (pelvis) and 0.81-0.83 (lower extremities), compared to gastrointestinal air motion (0.52-0.58). CONCLUSION: Single-echo MRT exhibited better precision than dual-echo MRT. Body fat-based field-drift correction significantly improved MRT accuracy. Pretreatment bulk motion showed improved prediction of acceptable MRT temporal precision over gastrointestinal air motion.

Infrared Thermometry and Thermography in Detecting Skin Temperature Variations to Predict Venous Leg Ulcer Reulceration: A Case Report.

BACKGROUND: We aimed to determine whether monitoring skin temperature (Tsk) over recently healed venous leg ulcers (VLUs) can provide an objective approach to predicting reulceration. The cases presented in this article were part of a larger, multisite, 6-month randomized clinical trial of a cooling intervention to prevent ulcer recurrence among patients with chronic venous disease (CVD) and with recently healed VLUs. CASES: We report a series of four patients with CVD, three experienced VLU reulceration, and one case remained free of recurrence. Assessments of recurrence likelihood is based on daily patient Tsk self-reports using a handheld infrared (IR) thermometer and clinic visits using a combination digital and long-wave IR camera. All three cases with reulceration demonstrate a persistent 2°C above baseline average Tsk increase and a "dip-and-spike" pattern from -3°C to +5°C for several days prior to reulceration. In contrast, the patient who remained free of VLU recurrence showed a stable pattern of Tsk with minimal daily fluctuations. Thermal images showed Tsk of the affected extremity is warmer compared with the contralateral limb and increased between visits when ulcers recurred. CONCLUSION: Using IR devices to monitor Tsk among patients with CVD at risk of reulceration is an objective and reliable approach to detect changes over time. Consistent Tsk elevation over the affected area as compared to the contralateral limb and a "dip-and-spike" pattern may predict reulceration. Infrared devices showed effectiveness in detecting changes indicative of Tsk changes in recently healed leg skin over scar tissue after VLU healing.

Toward Accurate Photoluminescence Nanothermometry Using Rare-Earth Doped Nanoparticles for Biomedical Applications.

ConspectusPhotoluminescence nanothermometry can detect the local temperature at the submicrometer scale with minimal contact with the object under investigation. Owing to its high spatial resolution, this technique shows great potential in biomedicine in both fundamental studies as well as preclinical research. Photoluminescence nanothermometry exploits the temperature-dependent optical properties of various nanoscale optical probes including organic fluorophores, quantum dots, and carbon nanostructures. At the vanguard of these diverse optical probes, rare-earth doped nanoparticles (RENPs) have demonstrated remarkable capabilities in photoluminescence nanothermometry. They distinguish themselves from other luminescent nanoprobes owning to their unparalleled and versatile optical properties that include narrow emission bandwidths, high photostability, tunable lifetimes from microseconds to milliseconds, multicolor emissions spanning the ultraviolet, visible, and near-infrared (NIR) regions, and the ability to undergo upconversion, all with excitation of a single, biologically friendly NIR wavelength. Recent advancements in the design of novel RENPs have led to new fundamental breakthroughs in photoluminescence nanothermometry. Moreover, driven by their excellent biocompatibility, both in vitro and in vivo, their implementation in biomedical applications has also gained significant traction. However, these nanoprobes face limitations caused by the complex biological environments, including absorption and scattering of various biomolecules as well as interference from different tissues, which limit the spatial resolution and detection sensitivity in RENP temperature sensing.Among existing approaches in RENP photoluminescence nanothermometry, the most prevalent implemented mechanisms either leverage the changes in the relative intensity ratio of two emission bands or exploit the lifetimes of various excited states. Photoluminescence intensity ratio (PLIR) nanothermometry has been the mainstream method owing to the readily available spectrometers for photoluminescence acquisition. Despite offering high temperature sensitivity and spatial resolution, this technique is restricted by tedious calibration and undesirable fluctuation in photoluminescence intensity ascribed to factors such as probe concentration, excitation power density, and biochemical surroundings. Lifetime-based nanothermometry uses the lifetime of a specific transition as the contrast mechanism to infer the temperature. This modality is less susceptible to various experimental factors and is compatible with a broader range of photoluminescence nanoprobes. However, due to relatively expensive and complex instrumentation, long data acquisition, and sophisticated data analysis, lifetime-based nanothermometry is still breaking ground with recently emerging techniques lightening its path.In this Account, we provide an overview of RENP nanothermometry and their applications in biomedicine. The architectures and luminescence mechanisms of RENPs are examined, followed by the principles of PLIR and lifetime-based nanothermometry. The in-depth description of each approach starts with its basic principle of accurate temperature sensing, followed by a critical discussion of the representative techniques, applications as well as their strengths and limitations. Special emphasis is given to the emerging modality of lifetime-based nanothermometry in light of the important new developments in the field. Finally, a summary and an outlook are provided to conclude this Account.

Accuracy of 3D real-time MRI temperature mapping in gel phantoms during microwave heating.

BACKGROUND: Interventional magnetic resonance imaging (MRI) can provide a comprehensive setting for microwave ablation of tumors with real-time monitoring of the energy delivery using MRI-based temperature mapping. The purpose of this study was to quantify the accuracy of three-dimensional (3D) real-time MRI temperature mapping during microwave heating in vitro by comparing MRI thermometry data to reference data measured by fiber-optical thermometry. METHODS: Nine phantom experiments were evaluated in agar-based gel phantoms using an in-room MR-conditional microwave system and MRI thermometry. MRI measurements were performed for 700 s (25 slices; temporal resolution 2 s). The temperature was monitored with two fiber-optical temperature sensors approximately 5 mm and 10 mm distant from the microwave antenna. Temperature curves of the sensors were compared to MRI temperature data of single-voxel regions of interest (ROIs) at the sensor tips; the accuracy of MRI thermometry was assessed as the root-mean-squared (RMS)-averaged temperature difference. Eighteen neighboring voxels around the original ROI were also evaluated and the voxel with the smallest temperature difference was additionally selected for further evaluation. RESULTS: The maximum temperature changes measured by the fiber-optical sensors ranged from 7.3 K to 50.7 K. The median RMS-averaged temperature differences in the originally selected voxels ranged from 1.4 K to 3.4 K. When evaluating the minimum-difference voxel from the neighborhood, the temperature differences ranged from 0.5 K to 0.9 K. The microwave antenna and the MRI-conditional in-room microwave generator did not induce relevant radiofrequency artifacts. CONCLUSION: Accurate 3D real-time MRI temperature mapping during microwave heating with very low RMS-averaged temperature errors below 1 K is feasible in gel phantoms. RELEVANCE STATEMENT: Accurate MRI-based volumetric real-time monitoring of temperature distribution and thermal dose is highly relevant in clinical MRI-based interventions and can be expected to improve local tumor control, as well as procedural safety by extending the limits of thermal (e.g., microwave) ablation of tumors in the liver and in other organs. KEY POINTS: Interventional MRI can provide a comprehensive setting for the microwave ablation of tumors. MRI can monitor the microwave ablation using real-time MRI-based temperature mapping. 3D real-time MRI temperature mapping during microwave heating is feasible. Measured temperature errors were below 1 °C in gel phantoms. The active in-room microwave generator did not induce any relevant radiofrequency artifacts.

An In Vivo Assessment of a Novel Temperature Control Flexible Ureteroscope System for Monitoring and Controlling Intrarenal Temperature During Flexible Ureteroscopy.

OBJECTIVE: To evaluate the efficacy of a novel temperature control flexible ureteroscope system in the precise monitoring and control of intrarenal temperature (IRT) during ureteroscopy. METHODS: We developed a novel temperature control flexible ureteroscope system (PT-Scope), including a temperature-monitoring ureteroscope and a irrigation-suction platform for temperature regulation. A porcine thermometry model was established to observe temperature changes under varying holmium laser powers (10, 20, 30 W) and irrigation rates (0, 20, 50 mL/min), utilizing percutaneous nephrostomy thermometry and PT-Scope measurements, with subsequent evaluation of temperature variations at different distances from the laser fiber tip. A porcine kidney stone model was established while porcine was randomly assigned to two groups: In the temperature control group, PT-Scope was connected to the irrigation-suction platform with temperature regulation, while in the nontemperature control group without temperature regulation. Comparative analysis was performed to evaluate differences in IRT between the two groups. RESULTS: Across various laser powers and irrigation rates, the temperature measurement capability of the PT-Scope was precise, demonstrating consistency with percutaneous nephrostomy temperature measurements. The temperature obtained from the PT-Scope reflect the temperature approximately 0.05 cm away from the fiber tip, whereas temperatures close to fiber tip were significantly higher. The peak temperature of the temperature control group vs nontemperature control group were 31.70 ± 2.609°C and 44.37 ± 3.318 °C, respectively (P < 0.01). The mean temperature of the temperature control group vs nontemperature control group was 27.40 ± 2.107 °C vs 35.9 ± 1.921 °C (P < 0.01). CONCLUSION: PT-Scope has demonstrated the capability to precisely monitor and control IRT within a safe threshold.

Magnetic resonance thermometry for hyperthermia in the oropharynx region.

Magnetic resonance thermometry (MRT) can measure in-vivo 3D-temperature changes in real-time and noninvasively. However, for the oropharynx region and the entire head and neck, motion potentially introduces large artifacts. Considering long treatment times of 60-90 min, this study aims to evaluate whether MRT around the oropharynx is clinically feasible for hyperthermia treatments and quantify the effects of breathing and swallowing on MRT performance. A 3D-ME-FGRE sequence was used in a phantom cooling down and around the oropharynx of five volunteers over ∼75 min. The imaging protocol consisted of imaging with acceleration (ARC = 2), number of image averages (NEX = 1,2 and 3). For volunteers, the acquisitions included a breath-hold scan and scans with deliberate swallowing. MRT performance was quantified in neck muscle, spinal cord and masseter muscle, using mean average error (MAE), mean error (ME) and spatial standard deviation (SD). In phantom, an increase in NEX leads to a significant decrease in SD, but MAE and ME were unchanged. No significant difference was found in volunteers between the different scans. There was a significant difference between the regions evaluated: neck muscle had the best MAE (=1.96 °C) and SD (=0.82 °C), followed by spinal cord (MAE = 3.17 °C, SD = 0.92 °C) and masseter muscle (MAE = 4.53 °C, SD = 1.16 °C). Concerning the ME, spinal cord did best, then neck muscle and masseter muscle, with values of -0.64 °C, 1.15 °C and -3.05 °C respectively. Breathing, swallowing, and different ways of imaging (acceleration and NEX) do not significantly influence the MRT performance in the oropharynx region. The ROI selected however, leads to significant differences.

Thermal mapping: Assessing the optimal sites for temperature measurement in the human body and emerging technologies.

Numerous body locations have been utilized to obtain an accurate body temperature. While some are commonly used, their accuracy, response time, invasiveness varies greatly, and determines their potential clinical and/or research use. This review discusses human body temperature locations, their accuracy, ease of use, advantages, and drawbacks. We explain the concept of core body temperature and which of the locations achieve the best correlation to this temperature. The body locations include axilla, oral cavity, rectum, digestive and urinary tracts, skin, tympanic, nasopharynx, esophagus, and pulmonary artery. The review also discusses the latest temperature technologies, heat-flux technology and telemetric ingestible temperature pills, and the body locations used to validate these devices. Rectal and esophageal measurements are the most frequently used.

Assessment of NIR-triggered PEG-coated NaGdF4:Tm3+/Yb3+bio-compatible upconversion nanoparticles for contrast enhancement in OCT imaging and optical thermometry.

In this investigation, we embarked on the synthesis of polyethylene glycol coated NaGdF4:Tm3+/Yb3+upconversion nanoparticles (UCNPs), aiming to assess their utility in enhancing image contrast within the context of swept source optical coherence tomography (OCT) and photo-thermal OCT imaging. Our research unveiled the remarkable UC emissions stemming from the transitions of Tm3+ions, specifically the1G4→3H6transitions, yielding vibrant blue emissions at 472 nm. We delved further into the UC mechanism, meticulously scrutinizing decay times and the nanoparticles' capacity to convert radiation into heat. Notably, these nanoparticles exhibited an impressive photo-thermal conversion efficiency of 37.5%. Furthermore, our investigations into their bio-compatibility revealed a promising outcome, with more than 90% cell survival after 24 h of incubation with HeLa cells treated with UCNPs. The nanoparticles demonstrated a notable thermal sensitivity of 4.7 × 10-3K-1at 300 K, signifying their potential for precise temperature monitoring at the cellular level.

2D ultrasound thermometry during thermal ablation with high-intensity focused ultrasound.

The clinical use of high intensity focused ultrasound (HIFU) therapy for noninvasive tissue ablation has recently gained momentum. Guidance is provided by either magnetic resonance imaging (MRI) or conventional B-mode ultrasound imaging, each with its own advantages and disadvantages. The main limitation of ultrasound imaging is its inability to provide temperature measurements over the ranges corresponding to the target temperatures during ablative thermal therapies (between 55 °C and 70 °C). Here, variations in ultrasound backscattered energy (ΔBSE) were used to monitor temperature increases in liver tissue up to an absolute value of 90 °C during and after HIFU treatment. In vitro experimental measurements were performed in 47 bovine liver samples using a toroidal HIFU transducer operating at 2.5 MHz to increase the temperature of tissues. An ultrasound imaging probe working at 7.5 MHz was placed in the center of the HIFU transducer to monitor the backscattered signals. The free-field acoustic power was set to 9 W, 12 W or 16 W in the different experiments. HIFU sonications were performed for 240 s using a duty cycle of 83 % to allow ultrasound imaging and raw radiofrequency data acquisition during exposures. Measurements showed a linear relationship between ΔBSE (in dB) and temperature (r = 0.94, p < 0.001) over a temperature range from 37 °C to 90 °C, with a high reliability of temperature measurements below 75 °C. Monitoring can be performed at the frame rate of ultrasound imaging scanners with an accuracy within an acceptable threshold of 5 °C, given the temperatures targeted during thermal ablations. If the maximum temperature reached is below 70 °C, ΔBSE is also a reliable approach for estimating the temperature during cooling. Histological analysis shown the impact of the treatment on the spatial arrangement of cells that can explain the observed variation of ΔBSE. These results demonstrate the ability of ΔBSE measurements to estimate temperature in ultrasound images within an effective therapeutic range. This method can be implemented clinically and potentially applied to other thermal-based therapies.

In situ temperature determination using magnetic resonance spectroscopy thermometry for noninvasive postmortem examinations.

Magnetic resonance spectroscopy (MRS) thermometry offers a noninvasive, localized method for estimating temperature by leveraging the temperature-dependent chemical shift of water relative to a temperature-stable reference metabolite under suitable calibration. Consequentially, this technique has significant potential as a tool for postmortem MR examinations in forensic medicine and pathology. In these examinations, the deceased are examined at a wide range of body temperatures, and MRS thermometry may be used for the temperature adjustment of magnetic resonance imaging (MRI) protocols or for corrections in the analysis of MRI or MRS data. However, it is not yet clear to what extent postmortem changes may influence temperature estimation with MRS thermometry. In addition, N-acetylaspartate, which is commonly used as an in vivo reference metabolite, is known to decrease with increasing postmortem interval (PMI). This study shows that lactate, which is not only present in significant amounts postmortem but also has a temperature-stable chemical shift, can serve as a suitable reference metabolite for postmortem MRS thermometry. Using lactate, temperature estimation in postmortem brain tissue of severed sheep heads was accurate up to 60 h after death, with a mean absolute error of less than 0.5°C. For this purpose, published calibrations intended for in vivo measurements were used. Although postmortem decomposition resulted in severe metabolic changes, no consistent deviations were observed between measurements with an MR-compatible temperature probe and MRS thermometry with lactate as a reference metabolite. In addition, MRS thermometry was applied to 84 deceased who underwent a MR examination as part of the legal examination. MRS thermometry provided plausible results of brain temperature in comparison with rectal temperature. Even for deceased with a PMI well above 60 h, MRS thermometry still provided reliable readings. The results show a good suitability of MRS thermometry for postmortem examinations in forensic medicine.

Implication of thermal signaling in neuronal differentiation revealed by manipulation and measurement of intracellular temperature.

Neuronal differentiation-the development of neurons from neural stem cells-involves neurite outgrowth and is a key process during the development and regeneration of neural functions. In addition to various chemical signaling mechanisms, it has been suggested that thermal stimuli induce neuronal differentiation. However, the function of physiological subcellular thermogenesis during neuronal differentiation remains unknown. Here we create methods to manipulate and observe local intracellular temperature, and investigate the effects of noninvasive temperature changes on neuronal differentiation using neuron-like PC12 cells. Using quantitative heating with an infrared laser, we find an increase in local temperature (especially in the nucleus) facilitates neurite outgrowth. Intracellular thermometry reveals that neuronal differentiation is accompanied by intracellular thermogenesis associated with transcription and translation. Suppression of intracellular temperature increase during neuronal differentiation inhibits neurite outgrowth. Furthermore, spontaneous intracellular temperature elevation is involved in neurite outgrowth of primary mouse cortical neurons. These results offer a model for understanding neuronal differentiation induced by intracellular thermal signaling.

Pixel Screening in Lifetime-Based Temperature Mapping Using ß-NaYF4:Nd3+,Yb3+ by Time-Gated Near-Infrared Fluorescence Imaging on Deep Tissue in Live Mice.

Near-infrared fluorescence (NIRF) thermometry is an emerging method for the noncontact measurement of in vivo deep temperatures. Fluorescence-lifetime-based methods are effective because they are unaffected by optical loss due to excitation or detection paths. Moreover, the physiological changes in body temperature in deep tissues and their pharmacological effects are yet to be fully explored. In this study, we investigated the potential application of the NIRF lifetime-based method for temperature measurement of in vivo deep tissues in the abdomen using rare-earth-based particle materials. ß-NaYF4 particles codoped with Nd3+ and Yb3+ (excitation: 808 nm, emission: 980 nm) were used as NIRF thermometers, and their fluorescence decay curves were exponential. Slope linearity analysis (SLA), a screening method, was proposed to extract pixels with valid data. This method involves performing a linearity evaluation of the semilogarithmic plot of the decay curve collected at three delay times after cutting off the pulsed laser irradiation. After intragastric administration of the thermometer, the stomach temperature was monitored by using an NIRF time-gated imaging setup. Concurrently, a heater was attached to the lower abdomens of the mice under anesthesia. A decrease in the stomach temperature under anesthesia and its recovery via the heater indicated changes in the fluorescence lifetime of the thermometer placed inside the body. Thus, NaYF4:Nd3+/Yb3+ functions as a fluorescence thermometer that can measure in vivo temperature based on the temperature dependence of the fluorescence lifetime at 980 nm under 808 nm excitation. This study demonstrated the ability of a rare-earth-based NIRF thermometer to measure deep tissues in live mice, with the proposed SLA method for excluding the noisy deviations from the analysis for measuring temperature using the NIRF lifetime of a rare-earth-based thermometer.

Agreement between three noninvasive temperature monitoring devices during spinal anaesthesia for caesarean delivery: a prospective observational study.

Hypothermia during obstetric spinal anaesthesia is a common and important problem, yet temperature monitoring is often not performed due to the lack of a suitable, cost-effective monitor. This study aimed to compare a noninvasive core temperature monitor with two readily available peripheral temperature monitors during obstetric spinal anaesthesia. We undertook a prospective observational study including elective and emergency caesarean deliveries, to determine the agreement between affordable reusable surface temperature monitors (Welch Allyn SureTemp® Plus oral thermometer and the Braun 3-in-1 No Touch infrared thermometer) and the Dräger T-core© (using dual-sensor heat flux technology), in detecting thermoregulatory changes during obstetric spinal anaesthesia. Predetermined clinically relevant limits of agreement (LOA) were set at ± 0.5 °C. We included 166 patients in our analysis. Hypothermia (heat flux temperature < 36 °C) occurred in 67% (95% CI 49 to 78%). There was poor agreement between devices. In the Bland-Altman analysis, LOA for the heat flux monitor vs. oral thermometer were 1.8 °C (CI 1.7 to 2.0 °C; bias 0.5 °C), for heat flux monitor vs. infrared thermometer LOA were 2.3 °C (CI 2.1 to 2.4 °C; bias 0.4 °C) and for infrared vs. oral thermometer, LOA were 2.0 °C (CI 1.9 to 2.2 °C; bias 0.1 °C). Error grid analysis highlighted a large amount of clinical disagreement between methods. While monitoring of core temperature during obstetric spinal anaesthesia is clinically important, agreement between monitors was below clinically acceptable limits. Future research with gold-standard temperature monitors and exploration of causes of sensor divergence is needed.

Thermometry mapping during CT-guided thermal ablations: proof of feasibility and internal validation using spectral CT.

Objective. Conventional computed tomography (CT) imaging does not provide quantitative information on local thermal changes during percutaneous ablative therapy of cancerous and benign tumors, aside from few qualitative, visual cues. In this study, we have investigated changes in CT signal across a wide range of temperatures and two physical phases for two different tissue mimicking materials, each.Approach. A series of experiments were conducted using an anthropomorphic phantom filled with water-based gel and olive oil, respectively. Multiple, clinically used ablation devices were applied to locally cool or heat the phantom material and were arranged in a configuration that produced thermal changes in regions with inconsequential amounts of metal artifact. Eight fiber optic thermal sensors were positioned in the region absent of metal artifact and were used to record local temperatures throughout the experiments. A spectral CT scanner was used to periodically acquire and generate electron density weighted images. Average electron density weighted values in 1 mm3volumes of interest near the temperature sensors were computed and these data were then used to calculate thermal volumetric expansion coefficients for each material and phase.Main results. The experimentally determined expansion coefficients well-matched existing published values and variations with temperature-maximally differing by 5% of the known value. As a proof of concept, a CT-generated temperature map was produced during a heating time point of the water-based gel phantom, demonstrating the capability to map changes in electron density weighted signal to temperature.Significance. This study has demonstrated that spectral CT can be used to estimate local temperature changes for different materials and phases across temperature ranges produced by thermal ablations.

Superparamagnetic iron oxide nanoparticle enhanced percutaneous microwave ablation: Ex-vivo characterization using magnetic resonance thermometry.

BACKGROUND: Percutaneous microwave ablation (pMWA) is a minimally invasive procedure that uses a microwave antenna placed at the tip of a needle to induce lethal tissue heating. It can treat cancer and other diseases with lower morbidity than conventional surgery, but one major limitation is the lack of control over the heating region around the ablation needle. Superparamagnetic iron oxide nanoparticles have the potential to enhance and control pMWA heating due to their ability to absorb microwave energy and their ease of local delivery. PURPOSE: The purpose of this study is to experimentally quantify the capabilities of FDA-approved superparamagnetic iron oxide Feraheme nanoparticles (FHNPs) to enhance and control pMWA heating. This study aims to determine the effectiveness of locally injected FHNPs in increasing the maximum temperature during pMWA and to investigate the ability of FHNPs to create a controlled ablation zone around the pMWA needle. METHODS: PMWA was performed using a clinical ablation system at 915 MHz in ex-vivo porcine liver tissues. Prior to ablation, 50 uL 5 mg/mL FHNP injections were made on one side of the pMWA needle via a 23-gauge needle. Local temperatures at the FHNP injection site were directly compared to equidistant control sites without FHNP. First, temperatures were compared using directly inserted thermocouples. Next, temperatures were measured non-invasively using magnetic resonance thermometry (MRT), which enabled comprehensive four-dimensional (volumetric and temporal) assessment of heating effects relative to nanoparticle distribution, which was quantified using dual-echo ultrashort echo time (UTE) subtraction MR imaging. Maximum heating within FHNP-exposed tissues versus control tissues were compared at multiple pMWA energy delivery settings. The ability to generate a controlled asymmetric ablation zone using multiple FHNP injections was also tested. Finally, intra-procedural MRT-derived heat maps were correlated with gold standard gross pathology using Dice similarity analysis. RESULTS: Maximum temperatures at the FHNP injection site were significantly higher than control (without FHNP) sites when measured using direct thermocouples (93.1 ± 6.0°C vs. 57.2 ± 8.1°C, p = 0.002) and using non-invasive MRT (115.6 ± 13.4°C vs. 49.0 ± 10.6°C, p = 0.02). Temperature difference between FHNP-exposed and control sites correlated with total energy deposition: 66.6 ± 17.6°C, 58.1 ± 8.5°C, and 20.8 ± 9.2°C at high (17.5 ± 2.2 kJ), medium (13.6 ± 1.8 kJ), and low (8.8 ± 1.1 kJ) energies, respectively (all pairwise p < 0.05). Each FHNP injection resulted in a nanoparticle distribution within 0.9 ± 0.2 cm radially of the injection site and a local lethal heating zone confined to within 1.1 ± 0.4 cm radially of the injection epicenter. Multiple injections enabled a controllable, asymmetric ablation zone to be generated around the ablation needle, with maximal ablation radius on the FHNP injection side of 1.6 ± 0.2 cm compared to 0.7 ± 0.2 cm on the non-FHNP side (p = 0.02). MRT intra-procedural predicted ablation zone correlated strongly with post procedure gold-standard gross pathology assessment (Dice similarity 0.9). CONCLUSIONS: Locally injected FHNPs significantly enhanced pMWA heating in liver tissues, and were able to control the ablation zone shape around a pMWA needle. MRI and MRT allowed volumetric real-time visualization of both FHNP distribution and FHNP-enhanced pMWA heating that was useful for intra-procedural monitoring. This work strongly supports further development of a FHNP-enhanced pMWA paradigm; as all individual components of this approach are approved for patient use, there is low barrier for clinical translation.

Technical advances in motion-robust MR thermometry.

Proton resonance frequency shift (PRFS) MR thermometry is the most common method used in clinical thermal treatments because of its fast acquisition and high sensitivity to temperature. However, motion is the biggest obstacle in PRFS MR thermometry for monitoring thermal treatment in moving organs. This challenge arises because of the introduction of phase errors into the PRFS calculation through multiple methods, such as image misregistration, susceptibility changes in the magnetic field, and intraframe motion during MRI acquisition. Various approaches for motion correction have been developed for real-time, motion-robust, and volumetric MR thermometry. However, current technologies have inherent trade-offs among volume coverage, processing time, and temperature accuracy. These tradeoffs should be considered and chosen according to the thermal treatment application. In hyperthermia treatment, precise temperature measurements are of increased importance rather than the requirement for exceedingly high temporal resolution. In contrast, ablation procedures require robust temporal resolution to accurately capture a rapid temperature rise. This paper presents a comprehensive review of current cutting-edge MRI techniques for motion-robust MR thermometry, and recommends which techniques are better suited for each thermal treatment. We expect that this study will help discern the selection of motion-robust MR thermometry strategies and inspire the development of motion-robust volumetric MR thermometry for practical use in clinics.