We have no source of funding for this article to acknowledge.

All human experiments were approved by the Institutional Research Ethics Board at Sunnybrook Health Sciences Centre.
1. Patient Identification
<ol>
	<li>Administer informed consent with the patient or substitute decision maker. Explain potential adverse events related to the procedure, such as bleeding and neurological deficits, to the patient.</li>
	<li>Assess the candidate patient for MRgFUS thalamotomy. A physician with expertise in movement disorder should perform the assessment. 
	...

<ol>
	<li>Louis, E. D., Ottman, R., Hauser, W. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=How+common+is+the+most+common+adult+movement+disorder?+Estimates+of+the+prevalence+of+essential+tremor+throughout+the+world.">How common is the most common adult movement disorder? Estimates of the prevalence of essential tremor throughout the world.</a> Mov Disord. 13, 5-10 (1998).</li><li>Louis, E. D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Treatment+of+essential+tremor:+are+there+issues+we+are+overlooking?.">Treatment of essential tremor: are there issues we are overlooking?.</a> Front Neurol. 2, 91 (2011).</li><li>Zesiewicz, T. A., Encarnacion, E., Hauser, R. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Management+of+essential+tremor.">Management of essential tremor.</a> Curr Neurol Neurosci Rep. 2 (4), 324-330 (2002).</li><li>Yu, H., Neimat, J. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+treatment+of+movement+disorders+by+deep+brain+stimulation.">The treatment of movement disorders by deep brain stimulation.</a> Neurotherapeutics. 5 (1), 26-36 (2008).</li><li>Niranjan, A., Raju, S. S., Kooshkabadi, A., Monaco, E., Flickinger, J. C., Lunsford, L. D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Stereotactic+radiosurgery+for+essential+tremor:+Retrospective+analysis+of+a+19-year+experience.">Stereotactic radiosurgery for essential tremor: Retrospective analysis of a 19-year experience.</a> Movement Disorders: Mov Disord. , (2017).</li><li>Lipsman, N., Schwartz, M. L., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=MR-guided+focused+ultrasound+thalamotomy+for+essential+tremor:+a+proof-of-concept+study.">MR-guided focused ultrasound thalamotomy for essential tremor: a proof-of-concept study.</a> The Lancet. Neurology. 12 (5), 462-468 (2013).</li><li>Elias, W. J., Lipsman, N., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+Randomized+Trial+of+Focused+Ultrasound+Thalamotomy+for+Essential+Tremor.">A Randomized Trial of Focused Ultrasound Thalamotomy for Essential Tremor.</a> N Engl J Med. 375 (8), 730-739 (2016).</li><li>Hynynen, K., Jolesz, F. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Demonstration+of+potential+noninvasive+ultrasound+brain+therapy+through+an+intact+skull.">Demonstration of potential noninvasive ultrasound brain therapy through an intact skull.</a> Ultrasound Med Biol. 24 (2), 275-283 (1998).</li><li>Hamani, C., Lozano, A. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Hardware-related+complications+of+deep+brain+stimulation:+a+review+of+the+published+literature.">Hardware-related complications of deep brain stimulation: a review of the published literature.</a> Stereotact Funct Neurosurg. 84, 248-251 (2006).</li><li>Lim, S. Y., Hodaie, M., Fallis, M., Poon, Y. Y., Mazzella, F., Moro, E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Gamma+knife+thalamotomy+for+disabling+tremor:+a+blinded+evaluation.">Gamma knife thalamotomy for disabling tremor: a blinded evaluation.</a> Arch Neurol. 67, 584-588 (2010).</li><li>King, N. K. K., Krishna, V., Basha, D., Elias, G., Sammartino, F., Hodaie, M., Lozano, A. M., Hutchison, W. D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Microelectrode+recording+findings+within+the+tractography-defined+ventral+intermediate+nucleus.">Microelectrode recording findings within the tractography-defined ventral intermediate nucleus.</a> J Neurosurg. 126, 1669-1675 (2017).</li></ol>

KH is an inventor on patents and patent applications related to neuroablation with focused ultrasound. NL and KH have served as paid consultants for Focused Ultrasound Foundation (FUSF). FUSF is an independent, non-profit organization whose objective is the advancement of research in focused ultrasound technology and its applications. YM, YH, BS, MLS, and NS have no conflicts to declare.

MRgFUS at high-intensity can noninvasively create an intracranial lesion. Current high-intensity MRgFUS with continuous wave mode at 650 kHz has been optimized for thermal ablation of deep brain structures, such as the Vim thalamus. The use of MRgFUS has some advantages over existing techniques such as DBS, gamma knife radiosurgery, or radiofrequency ablation for treatment-refractory ET. DBS is an open surgical procedure that can be associated with potential device-related complications, including hardware malfunctions, ...

Essential tremor (ET) is the most common movement disorder, with a prevalence of up to 4% among individuals 40 year of age or older1. It is characterized by a postural and intention tremor at a frequency of approximately 4 - 7 Hz. It typically affects the upper extremities as well as the head and voice but can also be seen in the legs. ET can be severely debilitating, affecting the ability to manage simple activities of daily living. 15 - 25% of patients are forced to retire prematurely as a result of ET, and 60% of patients do not apply for jobs or promotions due to uncontrollable shaking2. Despite the effectiveness of first line medical therapies, such as propranolol or primidone3, a significant proportion of patients cannot tolerate or are resistant to medical treatments. Patients who remain symptomatic and significantly disabled after trying at least two medications, or who develop intolerable side effects, are considered medication-refractory.
Medically-refractory cases of ET are eligible for surgical interventions. Targeting of the ventralis intermedius (Vim) nucleus of the thalamus, a key cerebello-motor relay structure, with deep brain stimulation (DBS)4 electrodes or radiofrequency ablation can help alleviate tremors5,6. However, both are open neurosurgical procedures, with potential complications including infection and hemorrhage. DBS further involves chronic implantation of an intracranial electrode and battery over the pectoralis major. Furthermore, patients require anesthetics, and in the case of DBS a general anesthetic, as well as hospital stays ranging from one to several days.
MR-guided Focused ultrasound (MRgFUS) is an emerging noninvasive technique to treat various neurologic and psychiatric disorders. The device consists of a helmet that focuses over 1000 ultrasound beams from independent transducers through the intact skull. High-intensity MRgFUS can generate heat at the target leading to coagulative necrosis. A multi-centered randomized sham-controlled trial of thalamotomy for essential tremor demonstrated 47% improvement in tremor score that was durable at 12 months7. This result has led to regulatory approval of MRgFUS as a treatment modality and the subsequent addition of MRgFUS to the clinician&#39;s armamentarium for tremor management. This protocol details the steps of patient selection, preparation, and sonication, as well as the important elements of patient follow-up.

<table>
	<tbody>
		<tr>
			<td>InSightec ExAblate Neuro system</td>
			<td>InSightec</td>
			<td></td>
			<td>The ExAblate Neuro consists of a helmet transducer with 1,024 independent elements, each with central frequency 650 kHz and is integrated with a 3 Tesla MR scanner.</td>
		</tr>
		<tr>
			<td>3 Tesla MRI scanner</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>MRI compatible Cosman-Roberts-Wells (CRW) stereotactic frame</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>20 mL of 1% lidocaine with 1:100,000 epinephrine</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>hair shaver/clipper</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>warming blanket</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>compression stockings</td>
			<td></td>
			<td></td>
			<td></td>
		</tr>
	</tbody>
</table>

mri-guided focused ultrasound thalamotomy for patients with medically-refractory essential tremor

Essential tremor (ET) is the most common type of tremor in adults. While ET does not result in decreased life expectancy, the disabilities associated with ET can have a significant impact on quality of life, mood, functional activities, and socialization. Patients suffering from ET not sufficiently treated with first line medications may be eligible for alternative strategies such as deep brain stimulation, radiofrequency ablation, and MRI guided focused ultrasound (MRgFUS). High-intensity MRgFUS is an emerging modality to treat ET, its attraction for patients being that it is noninvasive and associated with short recovery time, as patients are home the day after treatment. While MRgFUS centers are still limited, it will become important for clinicians to consider MRgFUS as a treatment alternative, particularly in the case of a patient for whom open surgery is contraindicated. This article outlines the steps of patient selection, equipment setup, sonication, and post-treatment follow-up, as well as critical steps to be aware of when performing a MRgFUS procedure.

Long-term reduction in tremor in the treated extremity is on average 50% at 3 months and 40% at 12 months. Treatment success can be immediately evaluated after sonication through radiologic findings of a lesion at the Vim (Figure 1) and performance on clinical measures such as the hand-drawn spiral test (Figure 2). Additionally, intraoperative MR thermography provides real-time feedback to the target temperature. A permanent lesi...

Watch this Scientific Journal Video about MRI-guided Focused Ultrasound Thalamotomy for Patients with Medically-refractory Essential Tremor at JoVE.com

MRI-guided Focused Ultrasound Thalamotomy for Patients with Medically-refractory Essential Tremor

High-intensity MRI guided focused ultrasound is an emerging noninvasive technique to precisely ablate brain tissue. It has been shown to be safe and effective in treating medically-refractory essential tremor. This article describes the protocol for thalamotomy from patient selection to equipment setup to post-treatment follow-up.

Essential tremor (ET) is the most common type of tremor in adults. While ET does not result in decreased life expectancy, the disabilities associated with ...

The overall goal of this magnetic resonance guided focused ultrasound is to treat patients with medically refractory essential tremor by thermal ablation of the ventral intermediate nucleus of the thalamus. This method will help us answer key questions in the field of neuroscience about less invasive treatments for treatment refractory essential tremor. The main advantages of this technique are that it's less invasive, feedback is immediate and possibly more cost-effective than other open neurosurgical approaches.Implications of this technique extends to treatment of other movement disorders such as Parkinson's disease. Our experiences with MR guided focus ultrasound can provide insight about motor circuits inside the brain. Multidisciplinary teamwork is important for a successful treatment.The patient should be seen by a movement disorder specialist to determine the suitability for this procedure. Before beginning the procedure, completely shave the head of the patient and check for scalp lesions. Have a neurosurgeon put the stereotactic frame in place and inject local anesthetic at the four pin sites.Place a rubber diaphragm on the patient's head to prevent leakage of the degassed water that circulates between the ultrasound transducers and the scalp and check the patient for metal pieces. Have the patient lie head first in the ultrasound helmet in the supine position and cover the patient with a warming blanket. Give the patient a stop button to allow pausing of the procedure at any time.Then, after performing a preliminary 3D localizer magnetic resonance scan and a t2 weighted sequence, contour any lesions on the scalp, calcifications in the brain or sinuses and air volumes as no-pass zones, so the transducers can avoid these specific areas. You have to customize the lesion to the patient. The width of the third ventricle may vary widely in elderly patients, and you have to be mindful of the internal capsule as you extend the lesion laterally.To select the target, start the anterior posterior commissure line at 25 percent of the intercommissural distance anterior to the posterior commissure, locating the target midway between points 14 millimeters lateral to the midline and 11.5 millimeters lateral to the lateral edge of the ventricle. To perform a test sonication, raise the transducer temperature in the target region to 45 degrees Celsius and verify the alignment of the heated volume to the expected target. Correct the alignment in all three dimensions and raise the temperature to approximately 50 degrees Celsius.Adjust the target according to the patient's responses and increase the energy in 0 to 2 degree increments to make a permanent lesion at the target around 55 to 60 degrees Celsius. You have to adjust the target according to the patient's real-time responses. A knowledge of neuroanatomy is critical.Obtain a second t2 weighted MRI to assess the lesion size and any evidence of adverse events such as hemorrhage. If the results are satisfactory, help the patient out of the scanner and remove the frame. After treatment, assess the patient's hand tremor.Admit the patient to a post surgical unit overnight for observation and perform a third MRI the next morning to confirm the presence of the lesion and to rule out any adverse events followed by a full neurological exam as outlined in the table. The success of the treatment can be immediately evaluated after sonication, through the radiologic observation of the lesion at the Vim as well as the patient's performance on clinical measures such as the Clinical Rating Scale for Tremor or CRST. The Archimedean spiral is a part of the CRST used to measure the severity of the essential tremor and to follow patients'improvement after treatment.The CRST also requires the patient to complete several line drawings which should also demonstrate significant improvement after treatment. With experience this procedure can be performed in between three to four hours. While performing this procedure it's important to remain in constant communication with both the patient and the rest of the team.After watching this video you should have a good understanding of how a team works together to perform a MR guided focus ultrasound thalamotomy for essential tremor. Focus ultrasound thalamotomy is an effective less invasive surgical procedure for patients with refractory essential tremor, that reduces the risks associated with open neurosurgical procedures. Researchers are also investigating the use of focus ultrasound in other neurologic and psychiatric disorders such as Parkinson's disease and obsessive compulsive disorder.

mri-guided-focused-ultrasound-thalamotomy-for-patients-with-medically

Research

JoVE Journal

Medicine

13.7K Görüntüleme.  Sunnybrook Health Sciences Centre. The overall goal of this magnetic resonance guided focused ultrasound is to treat patients with medically refractory essential tremor by thermal ablation of the ventral intermediate nucleus of the thalamus. This method will help us answer key questions in the field of neuroscience about less invasive treatments for treatment refractory essential tremor. The main advantages of this technique are that it's less invasive, feedback is immediate and possibly more cost-effective than other open neu...