Thermal dosimetry for bladder hyperthermia treatment. An overview.

The urinary bladder is a fluid-filled organ. This makes, on the one hand, the internal surface of the bladder wall relatively easy to heat and ensures in most cases a relatively homogeneous temperature distribution; on the other hand the variable volume, organ motion, and moving fluid cause artefacts for most non-invasive thermometry methods, and require additional efforts in planning accurate thermal treatment of bladder cancer. We give an overview of the thermometry methods currently used and investigated for hyperthermia treatments of bladder cancer, and discuss their advantages and disadvantages within the context of the specific disease (muscle-invasive or non-muscle-invasive bladder cancer) and the heating technique used. The role of treatment simulation to determine the thermal dose delivered is also discussed. Generally speaking, invasive measurement methods are more accurate than non-invasive methods, but provide more limited spatial information; therefore, a combination of both is desirable, preferably supplemented by simulations. Current efforts at research and clinical centres continue to improve non-invasive thermometry methods and the reliability of treatment planning and control software. Due to the challenges in measuring temperature across the non-stationary bladder wall and surrounding tissues, more research is needed to increase our knowledge about the penetration depth and typical heating pattern of the various hyperthermia devices, in order to further improve treatments. The ability to better determine the delivered thermal dose will enable clinicians to investigate the optimal treatment parameters, and consequentially, to give better controlled, thus even more reliable and effective, thermal treatments

Respiratory organ motion in interventional MRI : tracking, guiding and modeling

Respiratory organ motion is one of the major challenges in interventional MRI, particularly in interventions with therapeutic ultrasound in the abdominal region. High-intensity focused ultrasound found an application in interventional MRI for noninvasive treatments of different abnormalities. In order to guide surgical and treatment interventions, organ motion imaging and modeling is commonly required before a treatment start. Accurate tracking of organ motion during various interventional MRI procedures is prerequisite for a successful outcome and safe therapy. In this thesis, an attempt has been made to develop approaches using focused ultrasound which could be used in future clinically for the treatment of abdominal organs, such as the liver and the kidney. Two distinct methods have been presented with its ex vivo and in vivo treatment results. In the first method, an MR-based pencil-beam navigator has been used to track organ motion and provide the motion information for acoustic focal point steering, while in the second approach a hybrid imaging using both ultrasound and magnetic resonance imaging was combined for advanced guiding capabilities. Organ motion modeling and four-dimensional imaging of organ motion is increasingly required before the surgical interventions. However, due to the current safety limitations and hardware restrictions, the MR acquisition of a time-resolved sequence of volumetric images is not possible with high temporal and spatial resolution. A novel multislice acquisition scheme that is based on a two-dimensional navigator, instead of a commonly used pencil-beam navigator, was devised to acquire the data slices and the corresponding navigator simultaneously using a CAIPIRINHA parallel imaging method. The acquisition duration for four-dimensional dataset sampling is reduced compared to the existing approaches, while the image contrast and quality are improved as well. Tracking respiratory organ motion is required in interventional procedures and during MR imaging of moving organs. An MR-based navigator is commonly used, however, it is usually associated with image artifacts, such as signal voids. Spectrally selective navigators can come in handy in cases where the imaging organ is surrounding with an adipose tissue, because it can provide an indirect measure of organ motion. A novel spectrally selective navigator based on a crossed-pair navigator has been developed. Experiments show the advantages of the application of this novel navigator for the volumetric imaging of the liver in vivo, where this navigator was used to gate the gradient-recalled echo sequence

Magnetic resonance thermometry: methodology, pitfalls and practical solutions

Clinically established thermal therapies such as thermoablative approaches or adjuvant hyperthermia treatment rely on accurate thermal dose information for the evaluation and adaptation of the thermal therapy. Intratumoural temperature measurements have been correlated successfully with clinical end points. Magnetic resonance imaging is the most suitable technique for non-invasive thermometry avoiding complications related to invasive temperature measurements. Since the advent of MR thermometry two decades ago, numerous MR thermometry techniques have been developed, continuously increasing accuracy and robustness for in vivo applications. While this progress was primarily focused on relative temperature mapping, current and future efforts will likely close the gap towards quantitative temperature readings. These efforts are essential to benchmark thermal therapy efficiency, to understand temperature-related biophysical and physiological processes and to use these insights to set new landmarks for diagnostic and therapeutic applications. With that in mind, this review summarises and discusses advances in MR thermometry, providing practical considerations, pitfalls and technical obstacles constraining temperature measurement accuracy, spatial and temporal resolution in vivo. Established approaches and current trends in thermal therapy hardware are surveyed with respect to potential benefits for MR thermometry

Heating technology for malignant tumors: a review

The therapeutic application of heat is very effective in cancer treatment. Both hyperthermia, i.e., heating to 39-45 degrees C to induce sensitization to radiotherapy and chemotherapy, and thermal ablation, where temperatures beyond 50 degrees C destroy tumor cells directly are frequently applied in the clinic. Achievement of an effective treatment requires high quality heating equipment, precise thermal dosimetry, and adequate quality assurance. Several types of devices, antennas and heating or power delivery systems have been proposed and developed in recent decades. These vary considerably in technique, heating depth, ability to focus, and in the size of the heating focus. Clinically used heating techniques involve electromagnetic and ultrasonic heating, hyperthermic perfusion and conductive heating. Depending on clinical objectives and available technology, thermal therapies can be subdivided into three broad categories: local, locoregional, or whole body heating. Clinically used local heating techniques include interstitial hyperthermia and ablation, high intensity focused ultrasound (HIFU), scanned focused ultrasound (SFUS), electroporation, nanoparticle heating, intraluminal heating and superficial heating. Locoregional heating techniques include phased array systems, capacitive systems and isolated perfusion. Whole body techniques focus on prevention of heat loss supplemented with energy deposition in the body, e.g., by infrared radiation. This review presents an overview of clinical hyperthermia and ablation devices used for local, locoregional, and whole body therapy. Proven and experimental clinical applications of thermal ablation and hyperthermia are listed. Methods for temperature measurement and the role of treatment planning to control treatments are discussed briefly, as well as future perspectives for heating technology for the treatment of tumors

Recent technological advancements in radiofrequency- andmicrowave-mediated hyperthermia for enhancing drug delivery

Hyperthermia therapy is a potent enhancer of chemotherapy and radiotherapy. In particular, microwave (MW) and radiofrequency (RF) hyperthermia devices provide a variety of heating approaches that can treat most cancers regardless the size. This review introduces the physics of MW/RF hyperthermia, the current state-of-the-art systems for both localized and regional heating, and recent advancements in hyperthermia treatment guidance using real-time computational simulations and magnetic resonance thermometry. Clinical trials involving RF/MW hyperthermia as adjuvant for chemotherapy are also presented per anatomical site. These studies favor the use of adjuvant hyperthermia since it significantly improves curative and palliative clinical outcomes. The main challenge of hyperthermia is the distribution of state-of-the-art heating systems. Nevertheless, we anticipate that recent technology advances will expand the use of hyperthermia to chemotherapy centers for enhanced drug delivery. These new technologies hold great promise not only for (image-guided) perfusion modulation and sensitization for cytotoxic drugs, but also for local delivery of various compounds using thermosensitive liposomes

Image-guidance and computational modeling to develop and characterize microwave thermal therapy platforms

Doctor of PhilosophyDepartment of Electrical and Computer EngineeringPunit PrakashThis dissertation focuses on the development of magnetic resonance imaging (MRI)-guided microwave thermal therapy systems for driving experimental studies in small animals, and to experimentally validate computational models of microwave ablation, which are widely employed for device design and characterization. MRI affords noninvasive monitoring of spatial temperature profiles, thereby providing a means to to quantitatively monitor and verify delivery of prescribed thermal doses in experimental studies and clinical use, as well as a means to validate thermal profiles predicted by computational models of thermal therapy. A contribution of this dissertation is the development and demonstration of a system for delivering mild hyperthermia to small animal targets, thereby providing a platform for driving basic research studies investigating the use of heating as part of cancer treatment strategies. An experimentally validated 3D computational model was employed to design and characterize a non-invasive directional water-cooled microwave hyperthermia applicator for MRI guided delivery of hypethermia in small animals. Following a parametric model-based design approach, a reflector aperture angle of 120°, S-shaped monopole antenna with 0.6 mm displacement, and a coolant flow rate of 150 ml/min were selected as applicator parameters that enable conformal delivery of mild hyperthermia to tumors in experimental animals. The system was integrated with real-time high-field 14.1 T MRI thermometry and feedback control to monitor and maintain target temperature elevations in the range of 4 – 5 °C (hypethermic range). 2 - 4 mm diameter targets positioned 1 – 3 mm from the applicator surface were heated to hyperthermic temperatures, with target coverage ratio ranging between 76 - 93 % and 11 – 26 % of non-targeted tissue heated. Another contribution of this dissertation is using computational models to determine how the fibroids altered ablation profile of a microwave applicator for global endometrial ablation. Uterine fibroids are benign pelvic tumors located within the myometrium or endometrium,and may alter the profile of microwave ablation applicators deployed within the uterus for delivering endometrial ablation. A 3D computational model was employed to investigate the effect of 1 – 3 cm diameter uterine fibroids in different locations around the uterine cavity on endometrial ablation profiles of microwave exposure with a 915 MHz microwave triangular loop antenna. The maximum change in simulated ablation depths due to the presence of fibroids was 1.1 mm. In summary, this simulation study suggests that 1 – 3 cm diameter uterine fibroids can be expected to have minimal impact on the extent of microwave endometrial ablation patterns achieved with the applicator studied in this dissertation. Another contribution of this dissertation is the development of a method for experimental validation of 3D transient temperature profiles predicted by computational models of MWA. An experimental platform was developed integrating custom designed MR-conditional MWA applicators for use within the MR environment. This developed platform was employed to conduct 30 - 50 W, 5 - 10 min MWA experiments in ex vivo tissue. Microwave ablation computational models, mimicking the experimental setting in MRI, were implemented using the finite element method, and incorporated temperature-dependent changes in tissue physical properties. MRI-derived Arrhenius thermal damage maps were compared to Model-predicted ablation zone extents using the Dice similarity coefficient (DSC). Mean absolute error between MR temperature measurements and fiber-optic temperature probes, used to validate the accuracy of MR temperature measurements, during heating was in the range of 0.5 – 2.8 °C. The mean DSC between model-predicted ablation zones and MRI-derived Arrhenius thermal damage maps for 13 experimental set-ups was 0.95. When comparing simulated and experimentally (i.e. using MRI) measured temperatures, the mean absolute error (MAE %) relative to maximum temperature change was in the range 5 % - 8.5 %

Design and evaluation of a hybrid radiofrequency applicator for magnetic resonance imaging and RF induced hyperthermia: electromagnetic field simulations up to 14.0 Tesla and proof-of-concept at 7.0 Tesla

This work demonstrates the feasibility of a hybrid radiofrequency (RF) applicator that supports magnetic resonance (MR) imaging and MR controlled targeted RF heating at ultrahigh magnetic fields (B0>/=7.0T). For this purpose a virtual and an experimental configuration of an 8-channel transmit/receive (TX/RX) hybrid RF applicator was designed. For TX/RX bow tie antenna electric dipoles were employed. Electromagnetic field simulations (EMF) were performed to study RF heating versus RF wavelength (frequency range: 64 MHz (1.5T) to 600 MHz (14.0T)). The experimental version of the applicator was implemented at B0 = 7.0T. The applicators feasibility for targeted RF heating was evaluated in EMF simulations and in phantom studies. Temperature co-simulations were conducted in phantoms and in a human voxel model. Our results demonstrate that higher frequencies afford a reduction in the size of specific absorption rate (SAR) hotspots. At 7T (298 MHz) the hybrid applicator yielded a 50% iso-contour SAR (iso-SAR-50%) hotspot with a diameter of 43 mm. At 600 MHz an iso-SAR-50% hotspot of 26 mm in diameter was observed. RF power deposition per RF input power was found to increase with B0 which makes targeted RF heating more efficient at higher frequencies. The applicator was capable of generating deep-seated temperature hotspots in phantoms. The feasibility of 2D steering of a SAR/temperature hotspot to a target location was demonstrated by the induction of a focal temperature increase (DeltaT = 8.1 K) in an off-center region of the phantom. Temperature simulations in the human brain performed at 298 MHz showed a maximum temperature increase to 48.6C for a deep-seated hotspot in the brain with a size of (19x23x32)mm(3) iso-temperature-90%. The hybrid applicator provided imaging capabilities that facilitate high spatial resolution brain MRI. To conclude, this study outlines the technical underpinnings and demonstrates the basic feasibility of an 8-channel hybrid TX/RX applicator that supports MR imaging, MR thermometry and targeted RF heating in one device