MRI-guided focused ultrasound (MRgFUS) surgery is a treatment that utilizes Magnetic Resonance Imaging (MRI) for planning treatment, controlling closed-loop of energy deposition and target definition (Catane et al. 2007). This delivery therapy system allows people to monitor, localize and target in real time hence ablates the infected tissues without affecting the other body structures. This makes this type of therapy a good alternative to radiotherapy or surgery of unthreatening and malicious tumors. The MRgFUS has been approved for treating uterine fibroids and is undergoing some tests for treatment for brain, breast, prostate, and liver cancer. It is also used to reduce pain to patients suffering from bone metastasis. Also, this treatment can change cell membrane permeability to activate compounds for the targeted gene therapy or delivery of drugs. It provides new therapy approaches that can cause major changes to the management of the patient and some medical disciplines. The purpose of this paper is to create an understanding of the inherent ways in which MRgFUS can be used in the debilitating condition of bone metastasis.
Bone is one of the common tissues that cancer metastasizes. The rise in life expectancy has resulted in many patients been diagnosed with cancer cells which have increased the prevalence of bone metastases and in particular individuals with breast or prostate cancer (Holzapfel, Wagner, Loessner, Holzapfel, Thibaudeau, Crawford & Hutmacher, 2014). However, when chemotherapy manages cancer cells in other parts of the body, bone metastases requires an additional therapy that which helps to prevent problems in the skeletal muscles and improve the quality of life. The major symptom in bone metastases is the pain with about 50%-70% suffering from unadorned pain. Currently, most patients are using the external-beam radiation therapy which is a non-invasive standard type of treatment for reducing local pain. However, about 20%-30% of patients do not get the pain relieved, and instead, the pain recurs in about 25% of patients after using the external-beam radiation therapy.
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Biologic Effects of High-Intensity Focused Ultrasound
Focused ultrasound systems create audio energy by the use of a piezoelectric transducer that works at frequency of about 200 kHz to 4MHz. It intensifies the focal volume of 100-10,000w/cm squared, a high compression pressure of 70MPa and rare factional pressure of 20MPa. Due to this high energy levels, the interaction between the biologic tissues and the focused ultrasound beams lead to the rise in temperature over the treated number of tissues. For this reason, the increased temperature results in coagulative necrosis at a thermal range of approximately 65-85 degrees which depends on the co-efficiency of tissue absorption (Kennedy, 2014).
To get a greater rapid rise in temperature, each sonication is restricted to the volume of about 0.2-5 cubic millimeter with a considerably insignificant effect on the tissue. Sonication is limited to only a few seconds thereby reduces the potential blood flow on energy distribution and detrimental effects of perfusion. The ablation of large sections of the body requires overlaying of multiple sonications to form a homogeneous thermal destruction. Focus ultrasound is also connected with an equivalent non-thermal phenomenon called cavitation (Kennedy, 2014). This takes place when microbubbles form around a targeted tissue. When the volume of micro bubbles reaches the maximum level, they shrink and as a result, produce a micro-shock of waves that can damage the surrounding tissues. However, because their outcome is unpredictable and still under investigation, the cavitation process has been avoided in clinical applications.
Clinical Application of MR Imaging–guided Focused Ultrasound for Bone Ablation
The cortical bone absorbs the ultrasound to a rate of up to 50 times greater hence allows merely a small segment of the energy to infiltrate through the cortex. For pain to reduce in bone metastases, the energy on the upper surface of the cortical bone increases the temperature which helps determine the current damage adjacent to the periosteum. This is because it is the uppermost element of developed bone tissues. The treatment parameters used to control tumor depend on the tuning of the system to increase the levels of energy and time for sonication and which allows the heating temperatures beyond the cortex. These factors are used separately to enable the penetration of the inner cortical bone. In the disruption of the cortical bone, the ultrasound beam with high intensity is steered in a similar manner so as to protect soft-tissues (Catane, Beck, Rabin, Shabshin, Hengst & Kopelman, 2007)
Indications for Treatment and Patient Selection
MR imaging–guided focused ultrasound is known to treat bone metastases or myeloma in patients with malignancy (Liberman, Gianfelice, Inbar, Beck, Rabin, Shabshin, Hanannel, 2009). It is well known for its safety for patients receiving radiation and lack the necessary symptom relief or those who cannot undertake external beam radiation. It contains the exclusion and inclusion criteria for treatment. In the exclusion criteria, patients cannot be treated with MRgFUS due to some medical reasons. These reasons include general inconsistencies to MR, when the targeted section is located in the skull 1cm less from the nerve bundles and when the scarring is extensive in the path of the area that needs treatment. In the inclusion criteria, for patients to performing MRgFUS of bone metastases they must have treatable lesions in the ribs, shoulders, and pelvis. Also, the target lesions should be visible using computed tomographic images (CT) and should be accessible through the focused ultrasound beam. Also, the interfaces between the lesions and bones should be 10mm deep from the skin.
Guide for treatment
The first step of treatment is the lesion localization and characterizing is using both the CT and MR imaging to allow adequate planning for treatment. The CT is performed to evaluate the mineralized component in the lesions and the integrity of adjacent cortical bone. The MR is carried out with combination of T1 and T2 weighted morphologic. After that, the three-dimensional dynamic contrast material and the diffusion-weighted imaging sequences are performed to help obtain useful information to determine the effects of treatment during follow-up. Ultrasound beam conformation and getting the optimal acoustic window is the most critical part in performing MRgFUS. This is because air and gasses interfere with the proliferation of the ultrasound beam in the body thus concealing targets beyond interfaces. The effects in the interfaces require much attention because it is a potential site of reflection. In treating lesions along the ribs, it is necessary for ribs to have enough to prevent the energy from heating the lung tissues.
The second step of treatment is the anesthetization. Anesthetization depends on the location of the lesion and clinical data such as respirator risk factors, pharmacologic therapy, and infections. It is preferable to use local anesthetics because they are efficient in intraoperative anesthesia, has small side effects and guarantees patient’s safety. However, the use of general anesthetics is always limited to procedures which involve the upper trunk lesions. The next step is planning and treatment which is conducted when the patient is lying on a table in the MR imaging unit. The patient is placed in a position that the lesion is targeted directly on the focused ultrasound transducer.
Treatment plan consists of calibration, loading, segmentation, planning, verification and treatment stage. In the calibration stage, the physician selects and approves the preliminary orientation and position of the transducer on the lesion. In the loading stage, MR images are attained to start the treatment planning and the acquired CT images are used for the process of registration. In the segmentation stage, targeted areas such as the skin, bone cortex and surrounding areas of the target are defined annually. During the planning stage, the computerized software calculates the treatment plan automatically and generates it displaying the sonication areas. This plan takes into account the regions needing low energy density to protect the adjacent organs and tissues. The verification stage follows in which a test in low-energy sonication is done to confirm the path and to correct the direction of the ultrasound beam to the targeted area. The treatment stage begins when the physician proceeds in treating the lesions by the use of sonication with full energy in the affected areas.
Benefits of MRgFUS for bone metastases
MRgFUS is well known for its few benefits to the patient undergoing therapy. It is known to be a non-invasive treatment procedure in which every session of therapy is performed on an outpatient basis. In the case of experiencing discomfort, the patient returns to his or her normal activities the following day without any complications. This procedure does not have negative effects on the bone marrow, and no ionizing radiation exposure takes place. It can also be used to treat osteoblastic and osteolytic tumors. Retreating symptom recurrence is possible after the first therapy is another benefit. Additionally, it reduces the need for opioids and non-narcotic analgesics thus eliminate potential side effects from the medications.
In conclusion, MRgFUS is a therapy that relieves pain and improves the function in a patient with bone metastases. Its major advantage is its non-invasive nature and the ability to execute three-dimensional MR imaging visualization. It also has precise treatment planning and has continuous temperature mapping for treating tissues using MR thermometry. The thermometry method used for MRgFUS is independent and can be used in all stages of treatment. Given the effects of these clinically substantial results and covered by positive side effects, MRgFUS should be deliberated as a sustainable treatment alternative for bone metastases. However, further research is needed to assess the importance of MRgFUS in individuals with bone metastasis as the leading option of therapy.
References
Catane, R., Beck, A., Inbar, Y., Rabin, T., Shabshin, N., Hengst, S., ... & Kopelman, D. (2007). MR-guided focused ultrasound surgery (MRgFUS) for the palliation of pain in patients with bone metastases—preliminary clinical experience. Annals of Oncology , 18(1), 163- 167.
Holzapfel, B. M., Wagner, F., Loessner, D., Holzapfel, N. P., Thibaudeau, L., Crawford, R., ... & Hutmacher, D. W. (2014). Species-specific homing mechanisms of human prostate cancer metastasis in tissue engineered bone. Biomaterials , 35(13), 4108-4115.
Kennedy, J. E., Ter Haar, G. R., & Cranston, D. (2014). High intensity focused ultrasound: surgery of the future?. The British journal of radiology .
Liberman, B., Gianfelice, D., Inbar, Y., Beck, A., Rabin, T., Shabshin, N., ... & Hanannel, A. (2009). Pain palliation in patients with bone metastases using MR-guided focused ultrasound surgery: a multicenter study. Annals of surgical oncology , 16(1), 140-146.
