Magnetic resonance guided focused ultrasound thalamotomy for essential tremor

Magnetic resonance guided focused ultrasound thalamotomy for essential tremor

Magnetic resonance guided focused ultrasound is a minimally invasive surgical procedure for symptomatic treatment of Parkinson Disease. With this technology, the ventral intermediate nucleusSTN, and internal globus pallidus have been targeted for therapeutic cerebral ablation, while also minimizing the risk of hemorrhage and infection from more invasive neurosurgical procedures.

In a pilot study published in 2013, essential tremor improved in 15 patients treated with magnetic resonance guided focused ultrasound thalamotomy1).

Clinical trials have confirmed the efficacy of focused ultrasound (FUS) thalamotomy in essential tremor, but its effectiveness and safety for managing tremor-dominant Parkinson disease (TDPD) is unknown.

It might change the way that patients with essential tremor and potentially other disorders are treated 2).

Effectiveness

The post-treatment effectiveness was evaluated using the clinical rating scale for tremors. Thalamic MRgHIFU had substantial therapeutic effects on patients, based on MRgHIFU-mediated improvements in movement control and significant changes in brain mu rhythms. Ultrasonic thalamotomy may reduce hyper-excitable activity in the motor cortex, resulting in normalized behavioral activity after sonication treatment. Thus, non-invasive and spatially accurate MRgHIFU technology can serve as a potent therapeutic tool with broad clinical applications 3).

Safety

Magnetic resonance guided focused ultrasound (MRgFUS) for thalamotomy is a safe, effective and less-invasive surgical method for treating medication-refractory essential tremor (ET). However, several issues must be resolved before clinical application of MRgFUS, including optimal patient selection and management of patients during treatment 4).

Jung et al. found different MRI pattern evolution after MRgFUS for white matter and gray matter. Their results suggest that skull characteristics, such as low skull density, should be evaluated prior to MRgFUS to successfully achieve thermal rise 5).

Nursing management

In a large academic medical center in the mid-Atlantic region, the Department of Neurosurgery conducted a continued access study, recently approved by the Food and Drug Administration, to evaluate the effectiveness of transcranial FUS thalamotomy for the treatment of medication-refractory ET.

One patient’s experience will be introduced, including discussion of evidence-based treatment options for ET and information on the nursing management of the patient undergoing FUS thalamotomy 6).

Prospective randomized clinical trials

In a double-blinded, prospective, sham-controlled randomized controlled trial of MR-guided focused ultrasound thalamotomy for treatment of tremor-dominant PD, 62% of treated patients demonstrated improvement in tremor scores from baseline to 3 months postoperatively, as compared to 22% in the sham group. There has been only one open-label trial of MR-guided focused ultrasound subthalamotomy for patients with PD, demonstrating improvements of 71% for rigidity, 36% for akinesia, and 77% for tremor 6 months after treatment. Among the two open-label trials of MR-guided focused ultrasound pallidotomy for patients with PD, dyskinesia and overall motor scores improved up to 52% and 45% at 6 months postoperatively. Although MR-guided focused ultrasound thalamotomy is now approved by the U.S. Food and Drug Administration for treatment of parkinsonian tremor, additional high-quality randomized controlled trials are warranted and are underway to determine the safety and efficacy of MR-guided focused ultrasound subthalamotomy and pallidotomy for treatment of the cardinal features of PD. These studies will be paramount to aid clinicians to determine the ideal ablative target for individual patients. Additional work will be required to assess the durability of MR-guided focused ultrasound lesions, ideal timing of MR-guided focused ultrasound ablation in the course of PD, and the safety of performing bilateral lesions 7).

Case series

References

1)

Elias WJ, Huss D, Voss T, Loomba J, Khaled M, Zadicario E, Frysinger RC, Sperling SA, Wylie S, Monteith SJ, Druzgal J, Shah BB, Harrison M, Wintermark M. A pilot study of focused ultrasound thalamotomy for essential tremor. N Engl J Med. 2013 Aug 15;369(7):640-8. doi: 10.1056/NEJMoa1300962. PubMed PMID: 23944301.
2)

Lipsman N, Schwartz ML, Huang Y, Lee L, Sankar T, Chapman M, Hynynen K, Lozano AM. MR-guided focused ultrasound thalamotomy for essential tremor: a proof-of-concept study. Lancet Neurol. 2013 May;12(5):462-8. doi: 10.1016/S1474-4422(13)70048-6. Epub 2013 Mar 21. PubMed PMID: 23523144.
3)

Chang JW, Min BK, Kim BS, Chang WS, Lee YH. Neurophysiologic correlates of sonication treatment in patients with essential tremor. Ultrasound Med Biol. 2015 Jan;41(1):124-31. doi: 10.1016/j.ultrasmedbio.2014.08.008. Epub 2014 Oct 22. PubMed PMID: 25438838.
4)

Chang WS, Jung HH, Kweon EJ, Zadicario E, Rachmilevitch I, Chang JW. Unilateral magnetic resonance guided focused ultrasound thalamotomy for essential tremor: practices and clinicoradiological outcomes. J Neurol Neurosurg Psychiatry. 2015 Mar;86(3):257-64. doi: 10.1136/jnnp-2014-307642. Epub 2014 May 29. PubMed PMID: 24876191.
5)

Jung HH, Chang WS, Rachmilevitch I, Tlusty T, Zadicario E, Chang JW. Different magnetic resonance imaging patterns after transcranial magnetic resonance-guided focused ultrasound of the ventral intermediate nucleus of the thalamus and anterior limb of the internal capsule in patients with essential tremor or obsessive-compulsive disorder. J Neurosurg. 2015 Jan;122(1):162-8. doi: 10.3171/2014.8.JNS132603. PubMed PMID: 25343176.
6)

Shaw KD, Johnston AS, Rush-Evans S, Prather S, Maynard K. Nursing Management of the Patient Undergoing Focused Ultrasound: A New Treatment Option for Essential Tremor. J Neurosci Nurs. 2017 Aug 16. doi: 10.1097/JNN.0000000000000301. [Epub ahead of print] PubMed PMID: 28817495.
7)

Moosa S, Martínez-Fernández R, Elias WJ, Del Alamo M, Eisenberg HM, Fishman PS. The role of high-intensity focused ultrasound as a symptomatic treatment for Parkinson’s disease. Mov Disord. 2019 Jul 10. doi: 10.1002/mds.27779. [Epub ahead of print] Review. PubMed PMID: 31291491.

Magnetic resonance perfusion imaging in glioblastoma

Indications

Magnetic resonance perfusion imaging, may:

Provide a noninvasive diagnostic tool for properly grading lesions.

Identifying the most malignant region of a tumor for guiding biopsy

Monitoring response to therapy that may precede conventionally assessed changes in tumor morphology and enhancement characteristics.

May help quantitatively predict recurrent glioblastoma/progression for glioblastomas. The active tumor histological fraction correlated with quantitative radiologic measurements including rCBV and rCBF.

The dominant predictors of OS are normalized perfusion parameters Normalized Relative Tumor Blood Volume (n_rTBV) and Normalized Relative Tumor Blood Flow (n_rTBF). Pre-operative perfusion imaging may be used as a surrogate to predict glioblastoma aggressiveness and survival independent of treatment 1).


For metastases, Perfusion MRI may not be as useful in predicting mean active tumor fraction (AT). Clinicians must be judicious with their use of MRP in predicting tumor recurrence and radiation necrosis 2).

While perfusion MRI is not the ideal diagnostic method for differentiating glioma recurrence from pseudoprogression, it could improve diagnostic accuracy. Therefore, further research on combining perfusion MRI with other imaging modalities is warranted 3).

Perfusion-weighted magnetic resonance imaging (PW-MRI) techniques, such as dynamic contrast-enhanced MRI (DCE-MRI) and dynamic susceptibility contrast-MRI (DSC-MRI), have demonstrated much potential as powerful imaging biomarkers for glioma management as they can provide information of vascular hemodynamics 4) 5) 6).

PW-MRI is now rapidly expanding its application spectrum by noninvasively exploring the relationship between imaging parameters and the molecular characteristics of gliomas 7).


Dynamic contrast enhanced magnetic resonance imaging and Dynamic susceptibility weighted contrast enhanced perfusion imaging represent a widely accepted method to assess glioblastoma (GBM) microvasculature.

The aim of Navone et al. from the Laboratory of Experimental Neurosurgery and Cell Therapy, Neurosurgery Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Postgraduate School in Radiodiagnostics Department of Neuroradiology, Milan, was to investigate the correlation between plasma von Willebrand Factor (VWF):Ag, permeability and perfusion MRI parameters, and examine their potential in predicting GBM patient prognosis.

They retrospectively analysed pre-operative DCE-, DSC-MRI, and VWF:Ag level of 26 GBM patients. They assessed the maximum values of relative cerebral blood flow (rCBF) and volume (rCBV), volume transfer constant Ktrans, plasma volume (Vp) and reflux rate constant between fractional volume of the extravascular space and blood plasma (Kep). Non-parametric Mann-Withney test and Kaplan-Meier survival analyses were conducted and a p-value<0.05 was considered statistically significant.

The median VWF:Ag value was 248 IU/dL and the median follow-up duration was about 13 months. They divided patients according to low- and high-VWF:Ag and found significant differences in the median follow-up duration (19 months vs 10 months, p=0.04) and in Ktrans (0.31 min-1 vs 0.53 min-1, p=0.02), and Kep (1.79 min-1 vs 3.89 min-1, p=0.005) values. The cumulative 1-year survival was significantly shorter in patients with high-VWF:Ag and high-Kep compared to patients with low-VWF:Ag and low-Kep (37.5% vs. 68%, p = 0.05).

These findings, in a small group of patients, suggest a role for VWF:Ag, similar to Ktrans, and Kep as a prognostic indicator of postoperative GBM patient survival 8).

References

1)

Hou BL, Wen S, Katsevman GA, Liu H, Urhie O, Turner RC, Carpenter J, Bhatia S. MRI Parameters and Their Impact on the Survival of Patients with Glioblastoma: Tumor Perfusion Predicts Survival. World Neurosurg. 2018 Dec 26. pii: S1878-8750(18)32908-5. doi: 10.1016/j.wneu.2018.12.085. [Epub ahead of print] PubMed PMID: 30593971.
2)

Shah AH, Kuchakulla M, Ibrahim GM, Dadheech E, Komotar RJ, Gultekin SH, Ivan ME. The utility of Magnetic Resonance Perfusion imaging in quantifying active tumor fraction and radiation necrosis in recurrent intracranial tumors. World Neurosurg. 2018 Oct 9. pii: S1878-8750(18)32288-5. doi: 10.1016/j.wneu.2018.09.233. [Epub ahead of print] PubMed PMID: 30312826.
3)

Wan B, Wang S, Tu M, Wu B, Han P, Xu H. The diagnostic performance of perfusion MRI for differentiating glioma recurrence from pseudoprogression: A meta-analysis. Medicine (Baltimore). 2017 Mar;96(11):e6333. doi: 10.1097/MD.0000000000006333. PubMed PMID: 28296759; PubMed Central PMCID: PMC5369914.
4)

Jain R. Measurements of tumor vascular leakiness using DCE in brain tumors: clinical applications. NMR in Biomedicine. 2013;26(8):1042–1049. doi: 10.1002/nbm.2994.
5)

O’Connor J. P. B., Jackson A., Parker G. J. M., Roberts C., Jayson G. C. Dynamic contrast-enhanced MRI in clinical trials of antivascular therapies. Nature Reviews Clinical Oncology. 2012;9(3):167–177. doi: 10.1038/nrclinonc.2012.2.
6)

Barajas R. F. R., Cha S. Benefits of dynamic susceptibility-weighted contrast-enhanced perfusion MRI for glioma diagnosis and therapy. CNS oncology. 2014;3(6):407–419. doi: 10.2217/cns.14.44.
7)

Chung C., Metser U., Ménard C. Advances in magnetic resonance imaging and positron emission tomography imaging for grading and molecular characterization of glioma. Seminars in Radiation Oncology. 2015;25(3):164–171. doi: 10.1016/j.semradonc.2015.02.002.
8)

Navone SE, Doniselli FM, Summers P, Guarnaccia L, Rampini P, Locatelli M, Campanella R, Marfia G, Costa A. Correlation of preoperative Von Willebrand Factor with MRI perfusion and permeability parameters as predictors of prognosis in glioblastoma. World Neurosurg. 2018 Oct 9. pii: S1878-8750(18)32271-X. doi: 10.1016/j.wneu.2018.09.216. [Epub ahead of print] PubMed PMID: 30312827.

UpToDate: Dynamic Cervical Magnetic Resonance Imaging

Dynamic Cervical Magnetic Resonance Imaging

Dynamic MRI is useful to determine more accurately the number of levels where the spinal cord is compromised, and to better evaluate narrowing of the canal and intramedullary high-intensity signal (IHIS) changes. New information provided by flexion-extension MRI might change our strategy for CSM management 1).

Imaging of the cervical spine in functional positions has so far been limited to conventional Cervical spine x ray examinations or the scarcely available open magnetic resonance imaging (MRI). An MRI compatible positioning device allows MRI examinations in various positions and even in motion. In combination with high-resolution T2-weighted MRI it allows detailed functional imaging of the cervical spine and nerve roots.

The combination of a mechanical positioning device and a high-resolution 3D T2-weighted sequence (SPACE) on a conventional 1.5 T MRI allows kinematic imaging of the cervical spine as well as high-resolution imaging in the end positions, even in the presence of metal implants. In this proof of concept study a good visualization of narrowing of the spinal canal in functional positions could be achieved, showing the potential of MRI in functional positions for clinical and research applications 2).

The Dynamic Cervical Magnetic Resonance Imaging demonstrated a major number of findings and spinal cord compressions compared to the static exam. The dynamic exam is able to provide useful information in these patients, but Nigro et al., suggested a careful evaluation of the findings in the extension exam since they are probably over-expressed 3).

It is useful in correlating symptoms with the dynamic changes only noted on dMRI, and has reduced the incidence of misdiagnosis of myelopathy4).

In a study of Pratali et al., Dynamic cervical MRI was obtained using a standard protocol with the neck in neutral, flexion, and extension positions. The morphometric parameters considered were anterior length of the spinal cord (ALSC), posterior length of the spinal cord (PLSC), spinal canal diameter (SCD) and spinal cord width (SCW). Two observers analyzed the parameters independently, and the inter- and intra-observer reliabilities were assessed by the intraclass correlation coefficient (ICC).

18 patients were included in the study and all completed the dynamic MRI acquisition protocol. The inter- and intra-observer reliabilities demonstrated “almost perfect agreement” (ICC > 0.9, p < 0.001) for ALSC and PLSC in all positions. The SCD had inter- and intra-observer reliability classified as “almost perfect agreement” (ICC: 0.83-0.98, p < 0.001 and ICC: 0.90-0.99, p < 0.001, respectively) in all positions. The SCW had inter- and intra-observer reliability classified as “substantial agreement” (ICC: 0.73-0.94, p < 0.001 and ICC: 0.79-0.96, p < 0.001, respectively) in all positions. ALSC and PLSC in neutral, flexion and extension positions from the present study were significantly greater compared to the measurements previously published (P < 0.001).

The dynamic MRI protocol presented was safe and may allow a more complete evaluation of variations in the cervical spine in patients with CSM than traditional MRI protocols. The morphometric parameters based on this protocol demonstrated excellent inter- and intra-observer reliabilities 5).

References

1)

Zhang L, Zeitoun D, Rangel A, Lazennec JY, Catonné Y, Pascal-Moussellard H. Preoperative evaluation of the cervical spondylotic myelopathy with flexion-extension magnetic resonance imaging: about a prospective study of fifty patients. Spine (Phila Pa 1976). 2011 Aug 1;36(17):E1134-9. doi: 10.1097/BRS.0b013e3181f822c7. PubMed PMID: 21785299.

2)

Gerigk L, Bostel T, Hegewald A, Thomé C, Scharf J, Groden C, Neumaier-Probst E. Dynamic magnetic resonance imaging of the cervical spine with high-resolution 3-dimensional T2-imaging. Clin Neuroradiol. 2012 Mar;22(1):93-9. doi: 10.1007/s00062-011-0121-2. Epub 2011 Dec 23. PubMed PMID: 22193978.

3)

Nigro L, Donnarumma P, Tarantino R, Rullo M, Santoro A, Delfini R. Static and dynamic cervical MRI: two useful exams in cervical myelopathy. J Spine Surg. 2017 Jun;3(2):212-216. doi: 10.21037/jss.2017.06.01. PubMed PMID: 28744502; PubMed Central PMCID: PMC5506301.

4)

Kolcun JP, Chieng LO, Madhavan K, Wang MY. The Role of Dynamic Magnetic Resonance Imaging in Cervical Spondylotic Myelopathy. Asian Spine J. 2017 Dec;11(6):1008-1015. doi: 10.4184/asj.2017.11.6.1008. Epub 2017 Dec 7. Review. PubMed PMID: 29279758; PubMed Central PMCID: PMC5738303.

5)

Pratali RR, Smith JS, Ancheschi BC, Maranho DAC, Savarese A, Nogueira-Barbosa MH, Herrero CFPS. A Technique for Dynamic Cervical Magnetic Resonance Imaging Applied to Cervical Spondylotic Myelopathy: A Reliability Study. Spine (Phila Pa 1976). 2018 Jun 26. doi: 10.1097/BRS.0000000000002765. [Epub ahead of print] PubMed PMID: 29952883.
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