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. 
	NOTE: It is important to rule out differential diagnoses such as dystonic tremor, Parkinson&#39;s Disease, and psychogenic tremor. Further, the neurologist should assess whether adequate trials of medical treatments have been attempted, and the patient deemed treatment-refractory.</li>
	<li>Check for contraindications such as an inability to tolerate an MRI.</li>
	<li>Assess the patient&#39;s medical fitness along with an anesthetist. 
	NOTE: Active heart disease, impaired kidney function, and propensity for bleeding are all contraindications for MRgFUS.</li>
	<li>Obtain bloodwork such as complete blood cell count, electrolytes, creatinine, and coagulation panel as part of the screening process.</li>
	<li>Perform a full neurological exam (Table 1) and use the clinical rating scale for tremor (CRST) to document tremor and disability. It is useful to also administer a standard quality of life scale to capture this information at baseline and to follow it over time.</li>
</ol>
2. Imaging Setup
<ol>
	<li>Obtain a CT scan prior to the day of treatment to assess for any intracranial calcifications and skull thickness. 
	NOTE: The CT scan should have at least 512 by 512 resolution, 1 mm thickness with zero spacing, covering the entire skull from the very top to the skull-base.</li>
	<li>Obtain an MR scan prior to the day of treatment to rule out contraindications such as previous intracranial hemorrhage or brain tumor.</li>
	<li>Use a commercially available helmet transducer with 1,024 independent elements, each with central frequency 650 kHz and integrated with a 3 Tesla MR scanner8. MRI thermometry is available to provide real time feedback of the target temperature.</li>
</ol>
3. Patient Preparation
<ol>
	<li>Advise the patient not to take their medication for essential tremor on the day of treatment and not to have anything by mouth beginning at midnight the night before surgery.</li>
	<li>Check the patient into the hospital, typically through Same Day Surgery.</li>
	<li>Ensure the entire team is present: neurosurgeon, movement disorder neurologist, physicist, imaging technician, and anesthetist. 
	NOTE: An anesthetist should be available to support the patient throughout the procedure in case of discomfort, anxiety, and vertigo/vomiting, while keeping the patient conscious at all times.</li>
	<li>Place suction equipment nearby for emergency airway maintenance and peripheral intravenous lines in case medications need to be administered urgently.</li>
	<li>Attach non-invasive monitors of heart rate, electrocardiogram, blood pressure, and oxygen saturation.</li>
	<li>Insert a Foley catheter, if necessary, for the patient to empty his/her bladder.</li>
	<li>Put graduated compression stockings on the patient to help prevent deep venous thrombosis in the lower limbs.</li>
	<li>Carefully shave the hair completely and check for scalp lesions.</li>
	<li>Place the stereotactic frame with the help of a neurosurgeon and apply local anesthetic (e.g., lidocaine or bupivicaine) at the 4 pin sites.</li>
	<li>Place the rubber diaphragm on the patient&#39;s head. 
	NOTE: Because the space between the transducer and scalp is filled with degassed water, a rubber diaphragm encircles the patient&#39;s head to prevent the water from leaking. Cool water is circulated, carrying away any excess heat from the scalp.</li>
	<li>Ensure the patient does not have any ferrous components before entering the procedure room.</li>
	<li>Have the patient lie flat, headfirst into the ultrasound helmet.</li>
	<li>Cover the patient with a warming blanket to prevent hypothermia. 
	NOTE: The temperature in the treatment room is approximately 15 &#176;C.</li>
</ol>
4. Target Selection of the Vim nucleus of the thalamus
<ol>
	<li>Perform a preliminary 3D localizer MR scan and T2-weighted sequence with at least axial and sagittal planes immediately prior to sonication to register the patient to pre-treatment CT/MRI scans.</li>
	<li>Fuse the new scans with the pre-treatment MRI and CT.</li>
	<li>Contour any lesions on the scalp, calcifications in the brain, sinuses, and air volumes as no-pass zones so the transducers can avoid these specific areas.</li>
	<li>Choose the target on the axial T2 weighted image cutting through the anterior commissure (AC) and posterior commissure (PC). 
	NOTE: There are different approaches to identifying and targeting the Vim nucleus of the thalamus. Given that the Vim is not visible even on 3T images, its location is deduced relative to known anatomic landmarks (i.e., indirect targeting).
	<ol>
		<li>At the level of the AC-PC line, begin at 25% of the intercommissural distance, anterior to PC. This is typically approximately 6 mm. 
		NOTE: The average AC-PC distance in humans is 24 - 28 mm, and can range from 20 - 30 mm. Dividing the distance into quarters, one begins by defining the point that is &#188; the distance of the anterior-posterior distance, anterior to PC.</li>
		<li>Laterally, select a point midway between the point 14 mm lateral to midline and the point 11.5 mm lateral to the lateral edge of the ventricle at the level of the AC-PC plane.</li>
		<li>Make small adjustments according to the actual length and width of the specific patient&#39;s third ventricle and regional anatomy. 
		NOTE: Third ventricular width can vary widely, especially in elderly patients. It is important to be mindful of internal capsule fibers when determining the laterality of the proposed target. An individualized approach, taking into consideration the patient&#39;s specific anatomy, is critical.</li>
	</ol>
	</li>
</ol>
5. Ultrasound Delivery
<ol>
	<li>Provide a stop button for the patient so they can abort energy delivery at any time.</li>
	<li>Perform a test sonication at low energy by raising the temperature in the target region to around 45 &#176;C.</li>
	<li>Verify the alignment of the heating volume to the target and correct in all three dimensions</li>
	<li>Raise the temperature further to approximately 50 &#176;C.</li>
	<li>After each sonication, perform a screening exam of motor power and sensation to light touch along with a test for the patient&#39;s tremor. 
	NOTE: At this point, the patient may experience transient dizziness, tingling and/or numbness.</li>
	<li>Adjust the target (i.e., moving anterior if the patient reports parasthesias) according to the patient&#39;s responses before increasing the energy to make the permanent lesion around 55-60 oC.</li>
	<li>Repeat the sonication until the tremor is reduced to a satisfactory level. 
	NOTE: 12 - 29 sonications each with a duration of 10 - 25 s are typically administered in increments of 0, 1, or 2 &#176;C in an awake patient.</li>
</ol>
6. Post-treatment
<ol>
	<li>Immediately after treatment, perform a T2-weighted MRI to assess for lesion size and associated radiologic findings such as edema.</li>
	<li>Once satisfactory, take the patient out of the scanner and remove the frame.</li>
	<li>Check pin sites for bleeding. A few minutes of pressure will usually stop this.</li>
	<li>Perform another neurologic exam (Table 1). 
	NOTE: This exam is important to rule out any neurologic deficits such as paresthesia, weakness, speech or visual deficits.</li>
	<li>Admit the patient to a post-surgical unit overnight for observation.</li>
	<li>Perform an MRI on day one post-treatment to confirm the presence of the lesion and rule out any adverse events.</li>
	<li>Request assessment by a neurosurgeon if an adverse event (e.g., mass effect on imaging, intracranial hemorrhage, or decreased level of consciousness) is detected.</li>
	<li>Discharge the patient in the morning if they are doing well.</li>
</ol>
7. Follow-up
<ol>
	<li>Schedule the patient for their first follow-up visit approximately 1 week after treatment.</li>
	<li>Review the patient&#39;s tremor symptoms, side effects, medication changes, and neurologic exam.</li>
	<li>Perform the CRST and quality of life measure to document and follow tremor and disability.</li>
	<li>Document any adverse events including pin-site infection, motor deficits, sensory disturbances, and speech problems.</li>
	<li>Request assessment of an adverse event by a physician, if necessary. Request a CT scan if the patient has a new neurological deficit to rule out intracranial etiology such as hemorrhage.</li>
</ol>

<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 ...

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13.8K Views.  Sunnybrook Health Sciences Centre. 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. 

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

MRI-guided Disruption of the Blood-brain Barrier using Transcranial Focused Ultrasound in a Rat Model

Focused ultrasound (FUS) disruption of the blood-brain barrier (BBB) is an increasingly investigated technique for circumventing the BBB1-5. The BBB is a significant obstacle to pharmaceutical treatments of brain disorders as it limits the passage of molecules from the vasculature into the brain tissue to molecules less than approximately 500 Da in size6. FUS induced BBB disruption (BBBD) is temporary and reversible4 and has an advantage over chemical means of inducing BBBD by being highly localized. FUS induced BBBD provides a means for investigating the effects of a wide range of therapeutic agents on the brain, which would not otherwise be deliverable to the tissue in sufficient concentration. While a wide range of ultrasound parameters have proven successful at disrupting the BBB2,5,7, there are several critical steps in the experimental procedure to ensure successful disruption with accurate targeting. This protocol outlines how to achieve MRI-guided FUS induced BBBD in a rat model, with a focus on the critical animal preparation and microbubble handling steps of the experiment.

Microbubble-mediated focused ultrasound disruption of the blood-brain barrier (BBB) is a promising technique for non-invasive targeted drug delivery in the brain1-3. This protocol outlines the experimental procedure for MRI-guided transcranial BBB disruption in a rat model.

Focused ultrasound (FUS) disruption of the blood-brain barrier (BBB) is an increasingly investigated technique for circumventing the BBB1-5. The BBB is a ...

Computerized Dynamic Posturography for Postural Control Assessment in Patients with Intermittent Claudication

Computerized dynamic posturography with the EquiTest is an objective technique for measuring postural strategies under challenging static and dynamic conditions. As part of a diagnostic assessment, the early detection of postural deficits is important so that appropriate and targeted interventions can be prescribed. The Sensory Organization Test (SOT) on the EquiTest determines an individual&#39;s use of the sensory systems (somatosensory, visual, and vestibular) that are responsible for postural control. Somatosensory and visual input are altered by the calibrated sway-referenced support surface and visual surround, which move in the anterior-posterior direction in response to the individual&#39;s postural sway. This creates a conflicting sensory experience. The Motor Control Test (MCT) challenges postural control by creating unexpected postural disturbances in the form of backwards and forwards translations. The translations are graded in magnitude and the time to recover from the perturbation is computed.
Intermittent claudication, the most common symptom of peripheral arterial disease, is characterized by a cramping pain in the lower limbs and caused by muscle ischemia secondary to reduced blood flow to working muscles during physical exertion. Claudicants often display poor balance, making them susceptible to falls and activity avoidance. The Ankle Brachial Pressure Index (ABPI) is a noninvasive method for indicating the presence of peripheral arterial disease and intermittent claudication, a common symptom in the lower extremities. ABPI is measured as the highest systolic pressure from either the dorsalis pedis or posterior tibial artery divided by the highest brachial artery systolic pressure from either arm. This paper will focus on the use of computerized dynamic posturography in the assessment of balance in claudicants.

Individuals with intermittent claudication exhibit poor balance compared to healthy controls. Computerized dynamic posturography is an objective method for measuring an individual's postural responses to balance disturbances. This provides an objective reflection of the person&#x2019;s ability to respond to situations under which sensory stimuli are altered and unexpected perturbations occur.

Computerized dynamic posturography with the EquiTest is an objective technique for measuring postural strategies under challenging static and dynamic ...

Assessment of Vascular Function in Patients With Chronic Kidney Disease

Patients with chronic kidney disease (CKD) have significantly increased risk of cardiovascular disease (CVD) compared to the general population, and this is only partially explained by traditional CVD risk factors. Vascular dysfunction is an important non-traditional risk factor, characterized by vascular endothelial dysfunction (most commonly assessed as impaired endothelium-dependent dilation [EDD]) and stiffening of the large elastic arteries. While various techniques exist to assess EDD and large elastic artery stiffness, the most commonly used are brachial artery flow-mediated dilation (FMDBA) and aortic pulse-wave velocity (aPWV), respectively. Both of these noninvasive measures of vascular dysfunction are independent predictors of future cardiovascular events in patients with and without kidney disease. Patients with CKD demonstrate both impaired FMDBA, and increased aPWV. While the exact mechanisms by which vascular dysfunction develops in CKD are incompletely understood, increased oxidative stress and a subsequent reduction in nitric oxide (NO) bioavailability are important contributors. Cellular changes in oxidative stress can be assessed by collecting vascular endothelial cells from the antecubital vein and measuring protein expression of markers of oxidative stress using immunofluorescence. We provide here a discussion of these methods to measure FMDBA, aPWV, and vascular endothelial cell protein expression.

The degree of vascular dysfunction and contributing physiological mechanisms can be assessed in patients with chronic kidney disease by measuring brachial artery flow-mediated dilation, aortic pulse-wave velocity, and vascular endothelial cell protein expression.

Patients with chronic kidney disease (CKD) have significantly increased risk of cardiovascular disease (CVD) compared to the general population, and this ...

MRI-guided dmPFC-rTMS as a Treatment for Treatment-resistant Major Depressive Disorder

Here we outline the protocol for magnetic resonance imaging (MRI) guided repetitive transcranial magnetic stimulation (rTMS) to the dorsal medial prefrontal cortex (dmPFC) in patients with major depressive disorder (MDD). Technicians used a neuronavigation system to process patient MRIs to generate a 3-dimensional head model. The head model was subsequently used to identify patient-specific stimulatory targets. The dmPFC was stimulated daily for 20 sessions. Stimulation intensity was titrated to address scalp pain associated with rTMS. Weekly assessments were conducted on the patients using the Hamilton Rating Scale for Depression (HamD17) and Beck Depression Index II (BDI-II). Treatment-resistant MDD patients achieved significant improvements on both HAMD and BDI-II. Of note, angled, double-cone coil rTMS at 120% resting motor threshold allows for optimal stimulation of deeper midline prefrontal regions, which results in a possible therapeutic application for MDD. One major limitation of the rTMS field is the heterogeneity of treatment parameters across studies, including duty cycle, number of pulses per session and intensity. Further work should be done to clarify the effect of stimulation parameters on outcome. Future dmPFC-rTMS work should include sham-controlled studies to confirm its clinical efficacy in MDD.

Here we outline the procedure for MRI-guided repetitive transcranial magnetic stimulation to the dorsomedial prefrontal cortex as an experimental treatment for major depressive disorder.

Here we outline the protocol for magnetic resonance imaging (MRI) guided repetitive transcranial magnetic stimulation (rTMS) to the dorsal medial ...

Bedside Ultrasound for Guiding Fluid Removal in Patients with Pulmonary Edema: The Reverse-FALLS Protocol

Fluid retention is the most common risk factor for mortality and cardiovascular complications in patients with volume-overloaded disease states. The extent of diuresis or fluid removal is frequently determined by physical examination which is subject to inaccuracies.
Bedside ultrasound (US) is a portable tool that brings real-time diagnostic imaging to the patient's bedside. This versatile modality makes it possible for the clinician to investigate patients' extravascular and intravascular volume states. The extravascular volume, particularly in the case of pulmonary edema, can be quantitatively assessed by US of the anterior chest. Intravascular volume is estimated by visualizing the inferior vena cava (IVC) caliber. Taken together, the degree of extravascular lung water and the IVC caliber provide objective data that can guide the clinician to determine the level of diuresis needed to effectively yet safely treat pulmonary edema. 
The objective of this article is threefold: 1) to summarize the findings of previous studies on the efficacy of portable US to guide fluid management, 2) to describe a proposed ultrasound protocol to help guide fluid management, and 3) to elucidate techniques that address the measurement of intravascular and extravascular volumes using portable US.

We describe an imaging protocol that enables the clinician to visualize, in real-time, the patient&#39;s intravascular and extravascular space volumes and set diuresis and fluid removal parameters accordingly for the safe and efficient treatment of pulmonary edema.

Fluid retention is the most common risk factor for mortality and cardiovascular complications in patients with volume-overloaded disease states. The ...

Semi-quantitative Assessment Using [18F]FDG Tracer in Patients with Severe Brain Injury

Patients with severe traumatic brain injury (sTBI) have difficulty knowing whether they are accurately expressing their thoughts and emotions because of disorders of consciousness, disrupted higher brain function, and verbal disturbances. As a consequence of an insufficient ability to communicate, objective evaluations are needed from family members, medical staff, and caregivers. One such evaluation is the assessment of functioning brain areas. Recently, multimodal brain imaging has been used to explore the function of damaged brain areas. [18F]-fluorodeoxyglucose positron emission tomography-computed tomography ([18F]FDG-PET/CT) is a successful tool for examining brain function. However, the assessment of brain glucose metabolism based on [18F]FDG-PET/CT is not standardized and depends on several varying parameters, as well as the patient&#39;s condition. Here, we describe a series of semiquantitative assessment protocols for a region-of-interest (ROI) image analysis using self-produced [18F]FDG tracers in patients with sTBI. The protocol focuses on screening the participants, preparing the [18F]FDG tracer in the hot lab, scheduling the acquisition of [18F]FDG-PET/CT brain images, and measuring glucose metabolism using the ROI analysis from a targeted brain area.

Semi-quantitative Assessment Using [18F]FDG Tracer in Patients with Severe Brain Injury

[18F]-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography is useful for studying glucose metabolism related to brain function. Here, we present a protocol for an [18F]FDG tracer set-up and semiquantitative assessment of the region-of-interest analysis for targeted brain areas associated with clinical manifestations in patients with severe traumatic brain injury.

Patients with severe traumatic brain injury (sTBI) have difficulty knowing whether they are accurately expressing their thoughts and emotions because of ...

Fertility Preservation in Patients with Severe Ovarian Dysfunction

Ovarian function progressively declines during aging and in some pathophysiological conditions including karyotype abnormality, autoimmune diseases, chemo- and radiation-therapies, as well as ovarian surgeries. In unmarried women with severe ovarian dysfunction, fertility preservation is important for future pregnancies. Although oocyte cryopreservation is an established method for fertility preservation, these patients could only preserve a limited number of oocytes even after ovarian hyperstimulation, leading to repeated stimulations to ensure sufficient oocytes to guarantee future pregnancy. To solve this issue, we have recently developed a drug-free in vitro activation (IVA) procedure, which enable us to stimulate early stages of ovarian follicles to develop to the preantral follicle stage. These preantral follicles can respond to the unique protocol of gonadotropin stimulation, resulting in increased number of retrieved oocytes per ovarian stimulation for cryopreservation. The drug-free IVA comprised from the surgical approach and ovarian stimulation. We removed a part of cortex from one or both ovaries from patients under laparoscopic surgery. The ovarian cortical tissues were cut into small cubes to disrupt the Hippo signaling pathway and stimulate the development of early stage follicles. These cubes were grafted orthotropically into remaining ovaries as well as beneath the serosa of both Fallopian tubes. We have already published the surgical procedure of the drug-free IVA and the protocol of subsequent ovarian stimulation, but herein we present the details of laboratory methods required for drug-free IVA.

We present details of laboratory procedures for drug-free in vitro activation (IVA) of ovarian follicles for patients with severe ovarian dysfunction. This method could increase the number of retrievable oocytes per ovarian hyperstimulation and benefit fertility preservation for those patients.

Ovarian function progressively declines during aging and in some pathophysiological conditions including karyotype abnormality, autoimmune diseases, ...

Modified Posterior Vertebral Column Resection for Patients with Thoracolumbar Kyphotic Deformity

Old compression vertebrae fracture or congenital kyphoscoliosis with abnormal vertebral body development and other diseases that invade the spine may cause severe thoracolumbar kyphotic deformity, often accompanied by intractable low back pain or compression of the spinal cord, leading to severe neurological symptoms or even paralysis. If conservative treatment cannot relieve the symptoms or correct the deformities, surgical treatment is usually needed. For severe kyphotic deformity, reconstruction of the physiological curvature and rigid fixation determine the prognosis of the patients. Osteotomy and orthopedics are the standard procedure for deformities with severe compression of the front and middle column, but the trauma to the patients is high, with a long operation time and massive blood loss. To avoid these disadvantages, we have developed a modified technique to remove the diseased vertebra unilaterally. In this technique, we use a modified trephine to resect the vertebral columns like in the pedicle screw technique by adding a locking instrument that can restrict the trephine to lower the risk of osteotomy and shorten the surgery time and blood loss.

We describe a modified technique for resecting the posterior vertebral column unilaterally based on a modified trephine for patients with thoracolumbar kyphotic deformity.

Old compression vertebrae fracture or congenital kyphoscoliosis with abnormal vertebral body development and other diseases that invade the spine may ...

Enema of Traditional Chinese Medicine for Patients with Severe Acute Pancreatitis

Severe acute pancreatitis (SAP) is characterized by high mortality rates, numerous complications, and extreme difficulties in treatment. A traditional Chinese medicine (TCM) enema has been widely utilized in clinical and experimental studies of SAP. It has been demonstrated to have beneficial effects in protecting pancreatic function and delaying disease progression. The procedure of TCM enema is to perfuse the Chinese medicinal liquid of raw rhubarb (Rheum officinale Baill. DaHuang) from the anus into the rectum and colon. Basic steps of the procedure include boiling the herbal solution in advance, using a disposable enema kit to assist patients in taking a left lying position, raising the patient's hip 10 cm, and carefully inserting the enema 30-35 cm into the anus, with a drip speed of 60-80 drops/min. The medicine liquid temperature should be equivalent to the patient's body temperature, typically between 37-39 &#176;C. The end of the enema operation should be slow, and Tui na (massage therapy) should be administered before extubation. The medication liquid should be kept in the rectum for more than 1 h. After issuing an enema, it is essential to observe the patient's feces and abdomen, and to evaluate the remission of abdominal signs and symptoms.

An enema is a type of traditional Chinese medicine (TCM) therapy used to treat severe acute pancreatitis (SAP). The therapy involves instilling a TCM liquid into the rectum and colon through the anus to keep the liquid in the intestine, absorbing through the intestinal mucosa. This study aims to standardize the enema procedure for SAP patients.

Severe acute pancreatitis (SAP) is characterized by high mortality rates, numerous complications, and extreme difficulties in treatment. A traditional ...

Microscopic Cyst Resection for the Treatment of Patients Diagnosed with Epididymal Cyst

Epididymal cysts mostly occur in men aged 20-40 years old. Previous reports have covered concerns about postoperative complexes, including postoperative asoedema, hematoma, sustaining pain, and seminal tract obstruction in patients who have undertaken nonmicroscopic epididymal cyst resection or epididymal resection. Nonmicroscopic epididymal cyst surgery is suggested for patients with childbirth plans as a precaution. The treatment of male epididymal cysts via microtechnology is obviously a beneficial option; we took the lead in carrying out microscopic epididymal exploration and cyst resection surgery in China. From September 2017 to April 2021, 41 young and middle-aged male patients diagnosed with epididymal cysts underwent microtechnology treatment in a program titled &#34;microscopic epididymal exploration and cystectomy&#34;. The postoperative follow-up lasted for 3-50 months. The results confirmed that, as microscopic manipulation largely improved visualization of the subtle tissue structures of the epididymis, the cyst could be clearly dissected apart and completely removed intact under the microscope. Bleeding during the operation was significantly reduced (2-3 mL) and wound drainage was not required. According to follow-up data, microscopic treatment significantly reduced the incidence of postoperative scrotal hematoma, edema, and long-term postoperative pain, thereby promising a higher surgical success rate as well as recurrence prevention. Besides, preliminary experience and reflection suggest that microscopic epididymal exploration and cystectomy provide efficient preservation of the epididymal patency through refined treatment, while a better prognosis can be achieved. We recommend that surgery be carried out before the epididymal cyst develops to 0.8 cm in diameter, for fear that a larger epididymal cyst (&#62;0.9 cm in diameter) could cause the complete destruction of all tubules of the ipsilateral epididymis - a more severe case with damage to the testicular output network.

Here, we present a protocol to treat patients diagnosed with an epididymal cyst using microscopic cyst resection. Based on microscopic manipulation, a largely improved visualization of the subtle tissue structures of the epididymis was obtained, so the cyst could be clearly dissected apart and completely removed intact.

Epididymal cysts mostly occur in men aged 20-40 years old. Previous reports have covered concerns about postoperative complexes, including postoperative ...