Ultrasound Thermometry Research Articles

Real-time non-invasive control of ultrasound hyperthermia using high-frequency ultrasonic backscattered energy in ex vivo tissue and in vivo animal 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.

Deep-learning based insitu ultrasound thermometry for thermal ablation monitoring

Noninvasive in situ temperature measurement (thermometry) is an attractive means of mapping the region of thermal damage during thermal ablation treatments. Existing methods of ultrasound thermometry are ineffective beyond 50 °C due to multiple physical limitations, including a non-monotonic relationship between temperature and sound speed that reaches a plateau around 60 °C, tissue phase transitions and deformation. An ultrasound-based technology that can monitor treatment over the entire therapeutic temperature range is desirable clinically. This paper describes a deep learning-based approach that uses thermometry data from the periphery of the heating zone (where temperatures are less than 50 °C) to infer temperature throughout the treatment zone. Spatiotemporal 2D temperature maps from 3–12 s HIFU heating exposures (in 0.5 s increments) were generated (using COMSOL) with a subset used for training the network and the rest for testing. Peripheral temperature values (excluding the first 5 mm closest to the axial focus), scalar time values, and a binary flag indicating heating/cooling were inputs to the network, and the temperature profile axially through the HIFU focus was predicted. The temperature prediction accuracy was better than 0.5 °C during heating and cooling. This paper will also address robustness to noise in the input temperature measurements and discuss future directions including experiments with ultrasound backscatter data and strategies to explicitly incorporate heat diffusion physics into the learning paradigm.

Focused Ultrasound Thermometry: A Two-Dimensional Resistance Temperature Detector Array in a Tissue-Mimicking Material

A two-dimensional resistance temperature detector (RTD) array sensor for the measurement of temperature distribution inside a tissue-mimicking material was proposed to validate focused ultrasound (FUS) devices. The fully two-dimensional $10\times10$ RTD array sensor with 1 mm inter-RTD distance was fabricated on the $2.5~ \boldsymbol {\mu } \text{m}$ thick film and placed inside the tissue-mimicking material. The measurement uncertainty for the RTD array was 0.18 K. The temperature distribution inside the phantom caused by a FUS transducer was measured and compared depending on the input power and focal plane. A tissue-mimicking phantom with an implanted RTD array can be applied to validate the performance and safety of both high- and low-intensity focused ultrasound (HIFU and LIFU) devices.

Ultrasound Thermometry for HIFU-Therapy

Abstract High-Intensity Focused Ultrasound (HIFU) is an alternative tumour therapy with the ability for non-invasive thermal ablation of tissue. For a safe application, the heat deposition needs to be monitored over time, which is currently done with Magnetic Resonance Imaging. Ultrasound (US) based monitoring is a promising alternative, as it is less expensive and allows the use of a single device for both therapy and monitoring. In this work, a method for spatial and temporal US thermometry has been investigated based on simulation studies and in-vitro measurements. The chosen approach is based on the approximately linear dependence between temperature and speed of sound (SoS) in tissue for a given temperature range. By tracking the speckles of successive B-images, the possibility of detecting local changes in SoS and therefore in temperature is given. A speckle tracking algorithm was implemented for 2D and 3D US thermometry using a spatial compounding method to reduce artifacts. The algorithm was experimentally validated in an agar-based phantom and in porcine tissue for temperature rises up to △ 8°C. We used a focusing single element US transducer as therapeutic probe, a linear (/matrix array) transducer with 128 (/32∙32) elements for imaging and thermocouples for validation and calibration. In all experiments, both computational and in-vitro, we succeeded in monitoring the thermal induced SoS changes over time. The in-vitro measurements were in good agreement with the simulation results and the thermocouple measurements (rms temperature difference = 0.53 °C, rms correlation coefficient = 0. 96).

Noninvasive calibrated tissue temperature estimation using backscattered energy of acoustic harmonics

PurposeA real-time and non-invasive thermometry technique is essential in thermal therapies to monitor and control the treatment. Ultrasound is an attractive thermometry modality due to its relatively high sensitivity to change in temperature and fast data acquisition and processing capabilities. A temperature-sensitive acoustic parameter is required for ultrasound thermometry in order to track the changes in that parameter during the treatment. Currently, the main ultrasound thermometry methods are based on variation in the attenuation coefficient, the change in backscattered energy of the signal (CBE), the backscattered radio-frequency (RF) echo-shift due to change in the speed of sound and thermal expansion of the medium, and change in the amplitudes of the acoustic harmonics. In this work, an ultrasound thermometry method based on second harmonic CBE (CBEh2) and combined fundamental and second harmonic CBE (CBEcomb) is used to produce 2D temperature maps, detect localized heated region generated by low intensity focused ultrasound (LIFU), and control temperature in the heated region. Materials and methodsEx vivo pork muscle tissue samples were exposed to localized LIFU heating source and 2D temperature maps were produced from the RF data acquired by a 4.2 MHz linear array probe using a Verasonics Vantage™ ultrasound scanner (Verasonics Inc., Redmond, WA) after the exposure. Calibrated needle thermocouples were also placed in the ex vivo tissue sample close to the LIFU focal zone for temperature calibration purposes. The estimated temperature maps were the established echo-shift technique. A tissue motion compensation algorithm was also used to reduce the susceptibility to motion artifacts. Results2D temperature maps were generated using CBE of acoustic harmonic and echo-shift techniques. The results show a direct correlation between the CBE of acoustic harmonics and focal tissue temperature for a range of temperatures from 37 °C (baseline) to 47 °C. ConclusionsThe findings of this study show that the CBE of acoustic harmonics technique can be used to noninvasively estimate temperature change in tissue in the hyperthermia temperature range.

Ultrasound temperature control during short-term local heating of a test object by focused ultrasound

High Intensity Focused Ultrasound (HIFU) is widely used in modern medicine. One of the important applications is the ablation of internal organ tumors under the HIFU heating. During this procedure, it is necessary to monitor the temperature in healthy adjacent tissues. Ultrasound thermometry (UST) is a promising non-invasive method of temperature control. The paper presents implementation of the UST technique in case of short-term local heating. A new algorithm suggested for ultrasound data processing improves the accuracy of the ultrasound thermometry technique to 2 °C.

A Review of Ultrasound Thermometry Techniques

Acoustic thermometry is one of non-invasive methods to measure the temperature inside tissue area. Especially, when using the thermal therapy techniques such as High Intensity Focused Ultrasound (HIFU) and other thermal based methods, thermal assessment of heated area seems to be necessary. Some of acoustic properties of medium are temperature dependent; therefore, evaluation of temperature dependent parameters will be an indirect and non-invasive approach in thermometry. In this paper some of thermometry methods based on changes in acoustic properties of medium have been reviewed. The published methods are classified in two main categories: passive and active thermometry. In the passive thermometry, the thermal measurement probes, induced no acoustic signals to the medium, but they receive the radiated signals from the heated medium. In active method, the thermometry probe transmits a signal into the heated region and receives the echoes, then the received RF signals are processed in order to measure the temperature.

A Novel Theranostic Platform: Integration of Magnetomotive and Thermal Ultrasound Imaging With Magnetic Hyperthermia.

Nanotheranostic systems integrate therapeutic and diagnostic procedures using nanotechnology. This type of approach has enabled the development of methods for early detection and treatment of different pathologies. Magnetic hyperthermia (MH) has been proposed as an alternative or complementary method of cancer therapy. However, challenges such as delivering and localizing the magnetic nanoparticles (MNPs) within tissues and monitoring the temperature during the treatment hinder this technique to be effectively translated into a clinical routine. Therefore, in this study a theranostic platform has been proposed and examined to address two main issues, localizing MNPs and real-time temperature monitoring, for preclinical MH. The system integrates magnetomotive (MMUS) and thermal ultrasound imaging with MH. An ultrasound device was used to acquire MMUS images to detect MNPs, and ultrasound thermometry to monitor the temperature. This platform was designed such that a single coil generated the magnetic field for MMUS and MH. The feasibility of the system was examined using a tissue mimicking phantom containing an inclusion filled with zinc substituted magnetite NPs. These MNPs were effectively used as contrast agent for MMUS and to generate heat during MH. In addition to localizing MNPs, real-time two-dimensional temperature maps were obtained with substantial concordance (ρc > 0.97) with invasive measurements using fiber optic thermometer. The heating rate was proportional to the displacements in MMUS (r=0.92). Ultrasound thermometry was successfully used to monitor the temperature during MH. In addition, it was shown that acquiring MMUS images prior to MH can qualitatively predict the temperature distribution of the MNP-laden regions.

Method for estimating average grey-level's measurement uncertainty from ultrasound images for non-invasive estimation of temperature in different tissue types

The objective of this work is to assess, on metrological basis, the average grey-levels (AVGL) calculated from B-Mode images for estimating temperature variations non-invasively in different kinds of tissues. Thermal medicine includes several thermal therapies, being hyperthermia the most noted and well known. Recently, efforts have been made to understand the benefits of ultrasound hyperthermia at mild temperature levels, i.e., between 39 °C and 41 °C. Moreover, the best practices on ultrasound bio-effects research have been encouraged by recommending that temperature rise in the region of interest should be measured even when a thermal mechanism is not being tested. In this work, the average grey-levels (AVGL) calculated from B-Mode images were assessed for non-invasive temperature estimation in a porcine tissue sample containing two different tissue types, fat and muscle, with temperature varying from 35 °C to 41 °C. The sample was continuously imaged with an ultrasound scanner, and simultaneously the temperature was measured. The achieved results were assessed under the light of the measurement uncertainty in order to allow comparability among different ultrasound thermometry methods. The highest expanded uncertainty of estimating temperature variation using AVGL was determined as 0.68 °C.

Application of ultrasound thermometry technique in case of local HIFU heating of test-object

The present work is aimed at development of a method for estimation of the accuracy of ultrasound thermometry (UST) when applying during local HIFU heating of a tissue-mimicking material (TMM). The method is based on comparison of the ultrasound measurement results with a temperature field reconstructed inside the TMM using data of the infrared (IR) camera surface measurements. In the case presented, the HIFU transducer heated up the TMM by 30 °C for 10 s in the focus area. Ultrasound signals were processed using an in-house UST application software. A 3D temperature field inside the TMM was reconstructed using a method based on the neural network approach. As a result, it has been achieved a good agreement between the UST measurement data and the reconstructed temperature field, especially for the points along the HIFU transducer axis.

Preliminary analysis of ultrasound elastography imaging-based thermometry on non-perfused ex vivo swine liver.

Real-time monitoring of tissue temperature during percutaneous tumor ablation improves treatment efficacy, leading clinicians in adjustment of treatment settings. This study aims at assessing feasibility of ultrasound thermometry during laser ablation of biological tissue using a specific ultrasound imaging techniques based on elastography acoustic radiation force impulse (ARFI). ARFI uses high-intensity focused ultrasound pulses to generate 'radiation force' in tissue; this provokes tissue displacements trackable using correlation-based ultrasound methods: the sensitivity of shear waves velocity is able to detect temperature changes. Experiments were carried out using a Nd:YAG laser (power: 5W) in three non-perfused ex vivo pig livers. In each organ, a thermocouple was placed close to the applicator tip (distance range 1.5-2.5cm) used to record a reference temperature. Positioning of laser applicator and thermocouple was eco-guided. The organ was scanned by an echography system equipped with ARFI; propagation velocity was measured in a region of interest of 1 × 0.5cm located close to thermocouple, to investigate influence of tissue temperature on shear waves velocity. Shear wave velocity has a very low sensitivity to temperature up to 55-60°C, and in all cases, velocity is < 5ms-1; for temperature > 55-60°C, velocity shows a steep increment. The system measures a value "over limit", meaning a velocity > 5ms-1. Ultrasound thermometry during laser ablation of biological tissue based on elastography shows an abrupt output change at temperatures > 55-60°C. This issue can have a relevant clinical impact, considering tumor necrosis when temperature crosses 55°C to define the boundary of damaged volume.

In vivo evaluation of two-dimensional temperature variation in perirenal fat of pigs with B-mode ultrasound

Benefiting from their minimally or noninvasive nature, thermal therapies are becoming increasingly important in tumor treatment, in which real-time monitoring of in vivo temperature based on ultrasonic imaging has shown great promise. In this work, an improved dynamic frame selection algorithm and a modified adaptive filtering method were combined with a thermal expansion model, and in vivo temperature monitoring with improved accuracy was achieved. The ultimate aim being the use of thermometry in the thermal treatment of hypertension, experiments targeting the perirenal fat of living pigs were carried out, in which microwaves were applied as a heat source at different power levels. By comparing the echo shift of the ultrasound (US) and the temperature—sensed via a thermocouple—a constant temperature evaluation coefficient was determined. As the tissue was raised to 6.4, 9.8, and 19.3 °C above its base temperature, the root-mean-square evaluation error (ɛrms) was about 0.3, 0.5, and 0.8 °C, respectively. High precision and a high signal-to-noise ratio can help US thermometry play a more important role in monitoring the application of thermal therapies.

Development of Ultrasound Thermometry Technique Using Tissue-Mimicking Phantom

A phantom with heating of tissue-equivalent material has been designed to elaborate the method of ultrasound thermometry. Algorithms have been developed to evaluate backscatter ultrasound signals shift caused by temperature-sensitivity of the speed of sound. Time-dependent material temperature field needed for estimation of the method accuracy was measured with thermistor probes.

Ultrasound thermal monitoring with an external ultrasound source for customized bipolar RF ablation shapes.

Thermotherapy is a clinical procedure which delivers thermal energy to a target, and it has been applied for various medical treatments. Temperature monitoring during thermotherapy is important to achieve precise and reproducible results. Medical ultrasound can be used for thermal monitoring and is an attractive medical imaging modality due to its advantages including non-ionizing radiation, cost-effectiveness and portability. We propose an ultrasound thermal monitoring method using a speed-of-sound tomographic approach coupled with a biophysical heat diffusion model. We implement an ultrasound thermometry approach using an external ultrasound source. We reconstruct the speed-of-sound images using time-of-flight information from the external ultrasound source and convert the speed-of-sound information into temperature by using the a priori knowledge brought by a biophysical heat diffusion model. Customized treatment shapes can be created using switching channels of radio frequency bipolar needle electrodes. Simulations of various ablation lesion shapes in the temperature range of 21-59[Formula: see text]C are performed to study the feasibility of the proposed method. We also evaluated our method with ex vivo porcine liver experiments, in which we generated temperature images between 22 and 45[Formula: see text]C. In this paper, we present a proof of concept showing the feasibility of our ultrasound thermal monitoring method. The proposed method could be applied to various thermotherapy procedures by only adding an ultrasound source.

Velocimetric ultrasound thermometry applied to myocardium protection monitoring

Tissue temperature control during cardiac surgery is crucial for myocardial protection. To preserve the tissue, a hypothermic cardioplegia is applied in order to decrease the heart temperature down to around 10°C. The monitoring of the thermal evolution of the myocardium is then of importance to minimize deleterious effects on the heart. The present work aims at evaluating the potential of an ultrasonic velocimetric thermometry on the monitoring of in vitro tissues heating. An indentation process is first proposed to identify the experimental linear relationship linking, in myocardia, the speed of the ultrasonic longitudinal wave to the tissue temperature. An extension of this method based on the echo-tracking principle is then proposed to approach surgical conditions. Temperature changes are measured by monitoring the induced time delays of backscattered ultrasonic echoes. These results are compared to T-type thermocouple reference measurements. They are then discussed in terms of measurement precision and in situ applications.

Temperature monitoring by channel data delays: Feasibility based on estimated delays magnitude for cardiac ablation

Ultrasound thermometry is based on measuring tissue temperature by its impact on ultrasound wave propagation. This study focuses on the use of transducer array channel data (not beamformed) and examines how a layer of increased velocity (heat induced) affects the travel-times of the ultrasound backscatter signal. Based on geometric considerations, a new equation was derived for the change in time delay as a function of temperature change. The resulting expression provides insight into the key factors that link change in temperature to change in travel time. It shows that velocity enters in combination with heating geometry: complementary information is needed to compute velocity from the changes in travel time. Using the bio-heat equation as a second source of information in the derived expressions, the feasibility of monitoring the temperature increase during cardiac ablation therapy using channel data was investigated. For an intra-cardiac (ICE) probe, using this “time delay error approach” would not be feasible, while for a trans-esophageal array transducer (TEE) transducer it might be feasible.

Reconstruction of Internal Temperature Distribution in Solid Structure by Ultrasound Thermometry

Reconstruction of Internal Temperature Distribution in Solid Structure by Ultrasound Thermometry

Laser thermal therapy monitoring using complex differential variance in optical coherence tomography.

Conventional thermal therapy monitoring techniques based on temperature are often invasive, limited by point sampling, and are indirect measures of tissue injury, while techniques such as magnetic resonance and ultrasound thermometry are limited by their spatial resolution. The visualization of the thermal coagulation zone at high spatial resolution is particularly critical to the precise delivery of thermal energy to epithelial lesions. In this work, an integrated thulium laser thermal therapy monitoring system was developed based on complex differential variance (CDV), which enables the 2D visualization of the dynamics of the thermal coagulation process at high spatial and temporal resolution with an optical frequency domain imaging system. With proper calibration to correct for noise, the CDV-based technique was shown to accurately delineate the thermal coagulation zone, which is marked by the transition from high CDV upon heating to a significantly reduced CDV once the tissue is coagulated, in 3 different tissue types ex vivo: skin, retina, and esophagus. The ability to delineate thermal lesions in multiple tissue types at high resolution opens up the possibility of performing microscopicimage-guided procedures in a vast array of epithelial applications ranging from dermatology, ophthalmology, to gastroenterology and beyond.

Calibration and Evaluation of Ultrasound Thermography Using Infrared Imaging

Real-time monitoring of the spatiotemporal evolution of tissue temperature is important to ensure safe and effective treatment in thermal therapies including hyperthermia and thermal ablation. Ultrasound thermography has been proposed as a non-invasive technique for temperature measurement, and accurate calibration of the temperature-dependent ultrasound signal changes against temperature is required. Here we report a method that uses infrared thermography for calibration and validation of ultrasound thermography. Using phantoms and cardiac tissue specimens subjected to high-intensity focused ultrasound heating, we simultaneously acquired ultrasound and infrared imaging data from the same surface plane of a sample. The commonly used echo time shift-based method was chosen to compute ultrasound thermometry. We first correlated the ultrasound echo time shifts with infrared-measured temperatures for material-dependent calibration and found that the calibration coefficient was positive for fat-mimicking phantom (1.49 ± 0.27) but negative for tissue-mimicking phantom (−0.59 ± 0.08) and cardiac tissue (−0.69 ± 0.18°C-mm/ns). We then obtained the estimation error of the ultrasound thermometry by comparing against the infrared-measured temperature and revealed that the error increased with decreased size of the heated region. Consistent with previous findings, the echo time shifts were no longer linearly dependent on temperature beyond 45°C–50°C in cardiac tissues. Unlike previous studies in which thermocouples or water bath techniques were used to evaluate the performance of ultrasound thermography, our results indicate that high-resolution infrared thermography is a useful tool that can be applied to evaluate and understand the limitations of ultrasound thermography methods.

Spatial and Temporal Control of Hyperthermia Using Real Time Ultrasonic Thermal Strain Imaging with Motion Compensation, Phantom Study.

Mild hyperthermia has been successfully employed to induce reversible physiological changes that can directly treat cancer and enhance local drug delivery. In this approach, temperature monitoring is essential to avoid undesirable biological effects that result from thermal damage. For thermal therapies, Magnetic Resonance Imaging (MRI) has been employed to control real-time Focused Ultrasound (FUS) therapies. However, combined ultrasound imaging and therapy systems offer the benefits of simple, low-cost devices that can be broadly applied. To facilitate such technology, ultrasound thermometry has potential to reliably monitor temperature. Control of mild hyperthermia was previously achieved using a proportional-integral-derivative (PID) controller based on thermocouple measurements. Despite accurate temporal control of heating, this method is limited by the single position at which the temperature is measured. Ultrasound thermometry techniques based on exploiting the thermal dependence of acoustic parameters (such as longitudinal velocity) can be extended to create thermal maps and allow an accurate monitoring of temperature with good spatial resolution. However, in vivo applications of this technique have not been fully developed due to the high sensitivity to tissue motion. Here, we propose a motion compensation method based on the acquisition of multiple reference frames prior to treatment. The technique was tested in the presence of 2-D and 3-D physiological-scale motion and was found to provide effective real-time temperature monitoring. PID control of mild hyperthermia in presence of motion was then tested with ultrasound thermometry as feedback and temperature was maintained within 0.3°C of the requested value.