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 »  Patient Selectio...
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 » Future Applications
 » Disadvantages
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Table of Contents    
SYMPOSIUM
Year : 2020  |  Volume : 68  |  Issue : 8  |  Page : 202-205

MR-Guided High-Intensity Focused Ultrasound Lesioning: MRgHIFU Breathing Life in the Lost Art of Lesioning for Movement Disorders


1 Department of Neurosurgery, The Functional Neurosurgery Unit, The Focused Ultrasound Institute and Sackler School of Medicine, Tel Aviv University, Israel
2 Sackler School of Medicine, Tel Aviv University, Israel

Date of Web Publication5-Dec-2020

Correspondence Address:
Prof. Zion Zibly
Department of Neurosurgery and Head, The Focused Ultrasound Institute, The Chaim Sheba Medical Center
Israel
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0028-3886.302452

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 » Abstract 


Magnetic resonance-guided high-intensity focused ultrasound (MRgHIFU) is a well-established technology that has been developed during the last decade and is currently used in the treatment of a diverse range of neurodegenerative brain disorders and neuropsychiatric diseases. This innovative noninvasive technology uses nonionizing ultrasound waves to heat and thus ablate brain tissue in selected targets. In comparison with other lesioning and surgical techniques, MRgHIFU has the following advantages: noninvasive, an immediate clinical outcome with no risk of long-standing ionizing radiation injury, no need for general anesthesia, and no device implantation.


Keywords: Focused ultrasound, high-intensity focused ultrasound, MRgHIFU, transcranial-focused ultrasound
Key Message: Magnetic resonance guided focused ultrasound lesioning is a safe clinical alternative.


How to cite this article:
Zibly Z, Averbuch S. MR-Guided High-Intensity Focused Ultrasound Lesioning: MRgHIFU Breathing Life in the Lost Art of Lesioning for Movement Disorders. Neurol India 2020;68, Suppl S2:202-5

How to cite this URL:
Zibly Z, Averbuch S. MR-Guided High-Intensity Focused Ultrasound Lesioning: MRgHIFU Breathing Life in the Lost Art of Lesioning for Movement Disorders. Neurol India [serial online] 2020 [cited 2021 Mar 4];68, Suppl S2:202-5. Available from: https://www.neurologyindia.com/text.asp?2020/68/8/202/302452




The concept of focused ultrasound was first introduced in 1935.[1] Later studies done by Lynn and colleagues in the 1940s demonstrated the feasibility of creating an ablative lesion in bovine liver and animal brain tissue using focused ultrasound.[2],[3] It was not until Fry developed a focused ultrasound device to produce accurate lesions without damaging the surrounding tissue.[4]

First introduced as a commercial machine, “Sonablate 200” was produced in the United States by “Focused Surgery” aiming to treat hyperplasia and prostatic gland cancer. As for the treatment of brain diseases, the “ExAblate 2000” was the first magnetic resonance-guided high-intensity focused ultrasound (MRgHIFU) system to obtain the Food and Drug Administration (FDA) market approval and was produced by the Israeli-based innovator Insightec[5] [Figure 1].
Figure 1: “ExAblate 2000” the first MRgHIFU system to obtain FDA market approval

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In this paper, we will describe the current indication, studies, and future applications of MRgHIFU.


 » Patient Selection and Pretreatment Protocol Top


Before surgery, pretreatment brain magnetic resonance imaging (MRI) planning images are enquired. At our institution, we use either 3 T or 1.5 T images. Besides, it is mandatory to obtain thin slices computed tomography (CT) scan (0.625 mm slice thickness) to evaluate the skull density ratio (SDR). These images will be registered, merged, and used for target definition. SDR is the median ratio of the skull density between the outer and inner cortical bone. This ratio is a major criterion in patient selection with a direct correlation to procedure success, and MRgHIFU should be suggested to patients with an SDR of 0.4 or higher.[6]

With some similarity to radiofrequency lesioning done years ago for the treatment of movement disorders, MRgHIFU surgery is done as an awake procedure. Following fixation of the hamlet which contains 1024 ultrasound beam sources, the patient's head is secured to the MRI table and acquisition scans are done. Since ultrasound waves cannot cross air, the patient's hair needs to be thoroughly shaved and degassed water is used as a barrier. A round elastic silicon membrane is stretched around the patient's head to avoid spillage of the degassed water.

Following imaging acquisition, the target for lesioning is selected by the surgeon. Since microelectrode recording is nonfeasible (as MRgHIFU is an incision-less procedure), trail sonication is done with the escalation of the temperature to a non-ablative degree. One should remember that during sonication (transfer of the ultrasonic energy to the brain), real-time thermometry is done [Figure 2]. By doing so, transitional functional damage is done to the treated tissue, and clinical examination of the patient can help the surgeon localize the efficacy and proximity to eloquent structures.[7] Following both clinical and radiologic confirmation, a thermal lesion is done at the desired target with an elevation of the temperature to more than 55°C. This increase in temperature causes a highly accurate hyperthermic ablative necrosis that can be observed via intraoperative imaging studies during MRgHIFU [Figure 3]. Lesion volume depends on multiple factors but typically a 4–5 mm diameter lesion can be obtained at a peak sonication temperature of 57–60°C (T2-weighted-MRI [T2-WMRI] is typically used to measure the lesion size). The accuracy of MRgHIFU is less than 2 mm, which is comparable with radiosurgery and gamma knife.[8]
Figure 2: Real-time thermometry during MRgHIFU treatment

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Figure 3: Real-time T2-WMR images showing thermal lesioning of the VIM during MRgHIFU (arrow)

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With accumulating clinical and neuroradiological data from multiple experienced centers using MRgHIFU for the treatment of movement disorders, and establishing a database, outcomes will defiantly improve. Since most diseases progress with time, there might be a need to retreat a group of patients with disease progression and tremors recurrence, as the long-term durability of MRgHIFU is yet to be established.

Current and future applications of MRgHIFU are shown in [Table 1].
Table 1: Current and future applications of MRgHIFU

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 » Review of the Literature Top


The introduction of MRgHIFU for the treatment of essential tremor (ET) was done by Elias and colleagues in their pilot study comprising of 15 patients treated with unilateral ventral intermediate nucleus (VIM) thermal ablation.[9] In their study, they proved the efficacy and safety of the procedure with a marked reduction of tremors and improvement in the quality of life. Since then multiple studies and reports were done to prove and assess the efficacy, safety, and cost-effectiveness of MRgHIFU in comparison to traditional procedures for the treatment of movement disorders. Richard et al., in a systematic literature review, conducted to identify the clinical, health-related quality of life, and economics of movement disorder surgeries concluded that MRI-guided focused ultrasound (MRgFUS) has similar short-term cost-effectiveness compared to deep brain stimulation (DBS) surgery.[10] Halpern and colleagues reported in their study that when compared to DBS and radiosurgery, MRgHIFU thalamotomy is more effective than both.[11] In a meta-analysis, Nanda et al. reported transient dizziness as the most common complication (occurring in 45.5% of patients), followed by nausea and vomiting.[12] He additionally reported that the most common long-term complication was ataxia (occurring in 32.8%), followed by paresthesia (occurring in 25.1% of the patients). At 1 year, the ataxia had significantly recovered, and paresthesia became the most common persisting complication, at 15.3%.

For the treatment of non-ET tremors, Lozano in his study of three patients with Parkinson's disease (PD), two patients with dystonic tremor, and one patient with dystonia gene-associated tremor, who were treated with MRgHIFU targeting the VIM, reported a significant, immediate, and sustained improvement of the contralateral tremor.[13]

In patients with PD, there are published reports of MRgHIFU ablation of the subthalamic nucleus (STN) and the globus pallidus internus (GPi). Chang reported a 53% decrease in dyskinesia following unilateral MRgHIFU pallidotomy.[14] Overall, the clinical improvement of PD patients treated with GPi or pallidothalamic tract thermal ablation is lower compared to improvement achieved with DBS surgery.[6]


 » Future Applications Top


As MRgHIFU thermal ablative is the most studied mechanism, there are some clinical studies and reports of its use in the following areas:

Obsessive-compulsive disorder (OCD): Kim et al. in their report of 11 patients with treatment-refractory OCD treated via bilateral thermal ablation of the anterior limb of the internal capsule using MRgHIFU, showed a significant improvement in both depressive and anxiety symptoms.[15] Lipsman and his group examined the safety profile, clinical response, and imaging correlates of MRgHIFU bilateral anterior capsulotomy in patients with refractory OCD and major depressive disorder (MDD).[16] They reported no serious adverse effects with a positive response rate of 50%, with OCD patients showing a superior response rate.

Brain tumors and neuro-oncology: There have been several reports for using focused ultrasound as a thermal ablative procedure. Early in 2006, Ram reported a trial to treat patients with brain stem glioma, and later McDannols in his study reported a trial to treat three patients with high-grade brain tumors.[17],[18] Both studied could not be continued due to immature technical issues that did not enable sufficient accurate and volumetric thermal ablation. Further developments are needed to establish and use MRgHIFU for the treatment of brain tumors, and these are currently being investigated. These studies will probably include using microbubbles injections to enhance the efficacy of MRgHIFU.

Epilepsy and pain: The classic therapeutical approach to epilepsy is either ablation of the epileptogenic focus or disrupting the epileptogenic complex connectivity network. It is most appropriate to use MRgHIFU whenever there is an obvious target to be ablated, such as a hypothalamic hamartoma, cortical dysplasia, etc., Hoffman et al. described a computerized model for the treatment of medically refractory mesial temporal sclerosis (MTS) epilepsy patients requiring surgery. In the described model, MRgFUS surgical plans ablating sites of the posterior hippocampal disconnection were done and concluded that treatment with this modality is both feasible and safe.[19]

Zibly et al., in a phantom experiment, tested the feasibility, safety, and efficacy of MRgFUS for treating facet joint pain.[20] In their animal study, they proved that targeting the facet joint with energies of 150–450 J provides controlled and accurate heating at the facet joint edge without penetration to the vertebral body, spinal canal, or root foramina. Monteith et al. in a cadaver study demonstrated the feasibility of targeting the trigeminal root entry zone and was able to avoid technical obstacles such as bone and brain stem heating.[21]


 » Disadvantages Top


Currently, the FDA has not yet approved the use of MRgHIFU for bilateral thermal ablation, so only one side of the affected limbs can be treated. Clinical studies are being done to assess the safety and efficacy of bilateral ablation, and these are yet to be evaluated.[22]

The present MRgHIFU systems present a narrow therapeutic area which is of 3 cm radius around the mid-commissural point. This makes treatment possible by targeting the thalamus and the basal ganglia but reduces the treatment efficacy of cortical and subcortical regions.[6]

When passing through the inner and outer cortical table of the skull, the ultrasound waves may cause transient heating of the bone and even necrosis (asymptomatic).[22],[23] Due to a similar mechanism, the scalp is also subjected to overheating and there have been rare reports of scalp burns.[8]

Since MRgHIFU is an ablative procedure, neurological adverse effects can be immediate and long-lasting. The side effects are mainly attributed to the location of the thermal ablation and can be resolved with the resolution of perilesional edema.


 » Conclusion Top


Amid as a lost art, lesioning of brain tissue for the treatment of a diversity of central nervous system disorders, MRgHIFU is a promising flourishing noninvasive technology. It guarantees both patients and physicians, the ability to target deep brain areas in conjunction with the accuracy and feasibility of invasive stereotactic surgery. Future studies will undoubtfully expose new indications of its safe use in neurosurgery.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
 » References Top

1.
Gruetzmacher, J. Piezoelektrischer kristall mit ultraschallkonvergenz. Z. Physik 1935;96:342-9.  Back to cited text no. 1
    
2.
Lynn JG, Putnam TJ. Histology of cerebral lesions produced by focused ultrasound. Am J Pathol 1944;20:637-49.  Back to cited text no. 2
    
3.
Lynn JG, Zwemer RL, Chick AJ, Miller AE. A new method for the generation and use of focused ultrasound in experimental biology. J Gen Physiol 1942;26:179-93.  Back to cited text no. 3
    
4.
Jung NY, Chang JW. Magnetic resonance-guided focused ultrasound in neurosurgery: Taking lessons from the past to inform the future. J Korean Med Sci 2018;33:e279.  Back to cited text no. 4
    
5.
Food and Drug Administration Approval, ExAblate® 2000 System.  Back to cited text no. 5
    
6.
Krishna V, Sammartino F, Rezai A. A review of the current therapies, challenges, and future directions of transcranial focused ultrasound technology. JAMA Neurol 2018;75:246-54.  Back to cited text no. 6
    
7.
Harnof S, Zibly Z, Cohen Z, Shaw A, Schlaff C, Kassel NF. Cranial nerve threshold for thermal injury induced by MRI- guided high- intensity focused ultrasound (MRgHIFU): Preliminary results on an optic nerve model. IEEE Trans Ultrason Ferroelectr Freq Control 2013;60:702-5.  Back to cited text no. 7
    
8.
Martin E, Jeanmonod D, Morel A, Zadicario E, Werner B. High intensity focused Ultrasound for non invasive functional neurosurgery. Ann Neurol. 2009;66:858-61.  Back to cited text no. 8
    
9.
Elias WJ, Huss D, Voss T, Loomba J, Khaled M, Zadicario E, et al. A pilot study of focused ultrasound thalamotomy for essential tremor. N Engl J Med 2013;369:640-8.  Back to cited text no. 9
    
10.
Langford BE, Ridley CJA, Beale RC, Caseby SCL, Marsh WJ, Richard L. Focused ultrasound thalamotomy and other interventions for medication-refractory essential tremor: An indirect comparison of short-term impact on health-related quality of life. Value Health 2018;21:1168-75.  Back to cited text no. 10
    
11.
Ravikumar VK, Parker JJ, Hornbeck TS, Santini VE, Pauly KB, Wintermark M, et al. Cost-effectiveness of focused ultrasound, radiosurgery, and DBS for essential tremor. Mov Disord 2017;32:1165-73.  Back to cited text no. 11
    
12.
Mohammed N, Patra D, Nanda A. A meta-analysis of outcomes and complications of magnetic resonance-guided focused ultrasound in the treatment of essential tremor. Neurosurg Focus 2018;44:E4.  Back to cited text no. 12
    
13.
Fasano A, Llinas M, Munhoz RP, Hlasny E, Kucharczyk W, Lozano AM. MRI-guided focused ultrasound thalamotomy in non-ET tremor syndromes. Neurology 2017;89:771-5.  Back to cited text no. 13
    
14.
Na YC, Chang WS, Jung HH, Kweon EJ, Chang JW. Unilateral magnetic resonance guided focused ultrasound pallidotomy for Parkinson disease. Neurology 2015;85:549-51.  Back to cited text no. 14
    
15.
Kim SJ, Roh D, Jung HH, Chang WS, Kim C-H, Chang JW. A study of novel bilateral thermal capsulotomy with focused ultrasound for treatment-refractory obsessive-compulsive disorder: 2-year follow-up. J Psychiatry Neurosci 2018;43:327-37.  Back to cited text no. 15
    
16.
Davidson B, Hamani C, Rabin JS, Goubran M, Meng Y, Huang Y, et al. Magnetic resonance-guided focused ultrasound capsulotomy for refractory obsessive compulsive disorder and major depressive disorder: Clinical and imaging results from two phase I trials. Mol Psychiatry 2020;25:1946-57.  Back to cited text no. 16
    
17.
Ram Z, Cohen ZR, Harnof S, Tal S, Faibel M, Nass D, et al. Magnetic resonance imaging-guided, high-intensity focused ultrasound for brain tumor therapy. Neurosurgery 2006;59:949-55.  Back to cited text no. 17
    
18.
McDannold N, Clement GT, Black P, Jolesz F, Hynynen K. Transcranial magnetic resonance imaging- guided focused ultrasound surgery of brain tumors: Initial findings in 3 patients. Neurosurgery 2010;66:323-32.  Back to cited text no. 18
    
19.
Parker WE, Weidman EK, Chazen JL, Niogi SN, Uribe-Cardenas R, Kaplitt MG, et al. Magnetic resonance-guided focused ultrasound for ablation of mesial temporal epilepsy circuits: Modeling and theoretical feasibility of a novel noninvasive approach. J Neurosurg 2019;1-8. doi: 10.3171/2019.4.JNS182694.  Back to cited text no. 19
    
20.
Harnof S, Zibly Z, Shay L, Dogadkin O, Hanannel A, Inbar Y, et al. Magnetic resonance-guided focused ultrasound treatment of facet joint pain: Summary of preclinical phase. J Ther Ultrasound 2014;2:9.  Back to cited text no. 20
    
21.
Monteith SJ, Medel R, Kassell NF, Wintermark M, Eames M, Snell J, et al. Transcranial magnetic resonance-guided focused ultrasound surgery for trigeminal neuralgia: A cadaveric and laboratory feasibility study. J Neurosurg 2013;118:319-28.  Back to cited text no. 21
    
22.
Pinton G, Aubry JF, Bossy E, Muller M, Pernot M, Tanter M, et al. Attenuation, scattering and absorption of ultrasound in the skull bone. Med Phys 2012;39:299-307.  Back to cited text no. 22
    
23.
Pernot M, Aubry J-F, Tanter M, Andre F, Fink M. Prediction of the skull overheating during high intensity focused ultrasound transcranial brain therapy. IEEE; 2004.  Back to cited text no. 23
    


    Figures

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