High-Intensity Focused Ultrasound for Pain Management in Patients with Cancer

Abstract

Cancer-related pain affects up to 80% of patients with malignancies. Pain is an important distressing symptom that diminishes the quality of life and negatively affects the survival of patients. Opioid analgesics are generally the primary therapy for cancer-related pain, with surgery, radiation therapy, chemotherapy, and other interventions used in cases of treatment-resistant pain. These treatments, which can be associated with substantial side effects and systemic toxicity, may not be effective. High-intensity focused ultrasound is an entirely noninvasive technique that is approved for treatment of uterine fibroids, bone metastases, and essential tremors. With magnetic resonance imaging or ultrasonographic guidance, high-intensity ultrasound waves are focused on a small well-demarcated region to result in precise localized ablation. This treatment may represent a multimodality approach to treating patients with malignant diseases-facilitating pain palliation, enhanced local drug delivery and radiation therapy effects, and stimulation of anticancer specific immune responses, and potentially facilitating local tumor control. Focused ultrasound can be used to achieve pain palliation by producing several effects, including tissue denervation, tumor mass reduction, and neuromodulation, that can influence different pathways at the origin of the pain. This technology has several key advantages compared with other analgesic therapies: It is completely noninvasive, might be used to achieve rapid pain control, can be safely repeated, and can be used in combination with chemotherapy and radiation therapy to enhance their effects. Online supplemental material is available for this article. RSNA, 2018.

MRI‐guided treatment in the breast

“…The most used temperature‐sensitive sequence is represented by the proton resonance frequency (PRF) shift technique: it is based on the temperature dependence of the water proton‐resonance frequency shift, which approximately corresponds to 0.01 ppm per degree Celsius . After each sonication, sonication parameters (energy, power, and frequency) can be adjusted in order to reach the desired temperature within the focal point …”

“…47 The most used temperature-sensitive sequence is represented by the proton resonance frequency (PRF) shift technique: it is based on the temperature dependence of the water proton-resonance frequency shift, which approximately corresponds to 0.01 ppm per degree Celsius. 47,[51][52][53] After each sonication, sonication parameters (energy, power, and frequency) can be adjusted in order to reach the desired temperature within the focal point. 47 The main limit of the PRF shift method is represented by the lack of capability to correctly measure the temperature within the fat tissue, since there is no hydrogen bonding among the methylene protons that supply the bulk of the fat signal.…”

High-Intensity Focused Ultrasound Ablation of Pancreatic Cancer

“…The waves generated by each element interfere constructively only at a desired focal point. 16,17 While diagnostic US transducers operate at the pressures of 0.001 to 0.003 MPa, which corresponds to time-averaged intensity of 0.1 to 100 mW/cm 2 , HIFU transducers produce up to 70-MPa peak compressional pressures and up to 20-MPa peak rarefactional pressures, which correspond to intensities of up to 20,000 W/cm 14,16 at the focused spot. The lesion targeting and monitoring during HIFU treatment could be US-guided (USgHIFU) or MR-guided (MRgHIFU).…”

“…Several different sources of cancer-related pain can be controlled using the following procedures: ablation-induced fibrosis and shrinkage of the tumor mass lead to pain reduction by relieving the pressure on nearby nerves; tissue heating damages nociceptive fibers and decreases their density, resulting in local denervation; and cavitation and acoustic pressure can temporarily modify cell morphology, causing the dysfunction of membrane proteins and stretch-activated ion channels, with a resultant imbalance of the cation influx and subsequent alteration of the membrane potential. 17 These changes alter neuronal excitability and propagation of the action potential, with pain palliation achieved by means of neuromodulation of noxious stimuli in the central or peripheral nervous system. 33 In addition to the well-established effects just described, there may be other benefits, in using HIFU, which are being investigated in preclinical and early clinical studies.…”

HIFU for Bone Metastases and other Musculoskeletal Applications

“…When considering bone metastases, there are multiple mechanisms that can explain the effects of HIFU in terms of pain relief, including periosteum denervation, tumor debulking (with reduction in the pain related to the expansion of the mass), and the reduction of chemical mediators' release and the degree of osteoclast-mediated osteolysis. 20 MRgFUS has received U.S. Food and Drug Administration approval for pain palliation in patients with bone metastases. Pain treatment is reported to be effective in 60 to 100% of patients.…”