Noninvasive Thermometry in High-Intensity Focused Ultrasound Ablation Yufeng Zhou, PhD Abstract: High-intensity focused ultrasound (HIFU) is emerging as an effective and promising treatment modality for the formation of coagulative necrosis inside the cancer/tumor noninvasively. To guaran- tee the efficacy and efficiency of HIFU ablation, the temperature field and consequent thermal dose should be monitored accurately in a high temporal and spatial resolution in real time. However, because of the significant variations of the tissue properties and deep penetration of HIFU beam, especially in the abdominal application, noninvasive ther- mometry is a very challenging topic, which may hamper the wide ac- ceptance of HIFU by physicians worldwide. In this article, currently available thermometry techniques are reviewed, and their translation from hyperthermia range to the higher temperature for irreversible le- sion production is discussed. With the technology improvement and/ or development of new approaches, the performance of noninvasive thermometry may meet the clinical requirements. Key Words: noninvasive thermometry, high-intensity focused ultrasound (HIFU), coagulative necrosis, magnetic resonance (MR), sonography, microwave radiometer, fluorescence (Ultrasound Quarterly 2017;33: 253–260) S olid tumor and cancer are the second leading mortality rea- son for human beings. There are estimated 595,690 cancer deaths and 1.685 million new cases in 2016 in the United States. 1 Conventional treatment modalities are surgical removal, radiotherapy and chemotherapy, and thermal ablation (ie, radio- frequency, microwave, laser, cryoablation, ferromagnetic ablation, and irreversible electroporation). The complexity of anatomy may limit the applicability of surgery, and radiother- apy and chemotherapy have significant adverse effects (ie, cardiotoxicity and nephrotoxicity and immune suppression). Thermal ablation requires high expert skills for adaptation and has limitations of invasiveness and small thermal volumes. 2 High-intensity focused ultrasound (HIFU) was translated to the clinical trial in the middle of 1990s after the advances in clinical diagnosis and guidance, computer control, and the ultra- sound (US) transducer, although the concept was introduced in the 1950s. Tissue absorbs the acoustic energy and then converts it to thermal energy. As a result, the temperature at the focus of HIFU could reach over 65°C within seconds to generate irre- versible protein denaturation. The gap between the coagulative necrosis and normal tissue is only approximately 50 μm. There- fore, the target could be precisely and noninvasively ablated if scanning the focus throughout the whole tumor volume. In Asia and Europe, 100,000 patients with prostate, breast, pancre- atic, liver, kidney, and bone cancers and uterine fibroids have been involved in with quite promising results, such as longer survival time, improved life quality, and reduced metastasis possibility. 3 High-intensity focused ultrasound is especially useful in the treatment of deeply seated targets that are inacces- sible or difficult to reach. However, the clinical performance of HIFU is not always satisfactory, which may be due to the inability to monitor the temperature elevation and its distribution as well as the extent of tissue necrosis formation in real time or quasi-real time. Like the other thermal ablation modalities, one of the challenges is that cancer cells close to the boundary of the thermal lesion may not be completely destroyed because of the existence of rel- atively small cold spots, which may induce the cancer recur- rence and should be avoided. On the other hand, overheating in normal tissue could lead to unacceptable morbidity. In addi- tion, respiratory motion in the upper abdomen (ie, 10–26 mm and 10–40 mm motion of liver during quiet and deep inspira- tion, respectively 4 ) complicates HIFU ablation (ie, misfocusing of target and wide spread of thermal field). In comparison, respi- ratory motion in the pelvic is not significant. The imaging must be fast enough, not only to prevent motion-related blurring ef- fect but also to control the US beam steering in the planned son- ication region, because breath holds or general anesthesia or single lung ventilation to minimize the respiratory motion may not be applicable for all patients. Therefore, a good HIFU system does need not only effective therapy but also reliable and accurate monitoring approach to quantitatively determine the progress of ablation as a feedback to the control program for its appropriate end point. 3 Thermal dosimetry with 3-dimension (3D) tempera- ture distribution at the good resolution (ie, ~0.5°C) and intraop- erative detection of lesion formation are necessary and desirable for wide clinical acceptance of HIFU as a standardized protocol. THERMOMETRY APPROACHES A variety of thermometry approaches have been used in the hyperthermia and tissue ablation. Their working princi- ple, performance, and limitation in HIFU are introduced and discussed. Received for publication December 27, 2016; accepted March 27, 2017. School of Mechanical and Aerospace Engineering, Nanyang Technological Uni- versity, Singapore. The author declares no conflict of interest. Address correspondence to: Yufeng Zhou, PhD, School of Mechanical and Aerospace Engineering, Nanyang Technological University, 50 Nanyang Ave, Singapore, 639798 (e‐mail: yfzhou@ntu.edu.sg). Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved. DOI: 10.1097/RUQ.0000000000000300 Ultrasound Quarterly • Volume 33, Number 4, December 2017 www.ultrasound-quarterly.com 253 REVIEW ARTICLE Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.