Correlation between fractional anisotropy changes in the targeted ventral intermediate nucleus and clinical outcome after transcranial MR-guided focused ultrasound thalamotomy for essential tremor: results of a pilot study

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This study evaluated changes of fractional anisotropy (FA) in the ventral intermediate nucleus (VIM) of the thalamus after transcranial MR-guided focused ultrasound (TcMRgFUS) thalamotomy and their associations with clinical outcome.


Clinical and radiological data of 12 patients with medically refractory essential tremor (mean age 76.5 years) who underwent TcMRgFUS thalamotomy with VIM targeting were analyzed retrospectively. The Clinical Rating Scale for Tremor (CRST) score was calculated before and at 1 year after treatment. Measurements of the relative FA (rFA) values, defined as ratio of the FA value in the targeted VIM to the FA value in the contralateral VIM, were performed before thalamotomy, and 1 day and 1 year thereafter.


TcMRgFUS thalamotomy was well tolerated and no long-term complications were noted. At 1-year follow-up, 8 patients demonstrated relief of tremor (improvement group), whereas in 4 others persistent tremor was noted (recurrence group). In the entire cohort, mean rFA values in the targeted VIM before treatment, and at 1 day and 1 year after treatment, were 1.12 ± 0.15, 0.44 ± 0.13, and 0.82 ± 0.22, respectively (p < 0.001). rFA values were consistently higher in the recurrence group compared with the improvement group, and the difference reached statistical significance at 1 day (p < 0.05) and 1 year (p < 0.01) after treatment. There was a statistically significant (p < 0.01) positive correlation between rFA values in the targeted VIM at 1 day after thalamotomy and CRST score at 1 year after treatment. Receiver operating characteristic curve analysis revealed that the optimal cutoff value of rFA at 1 day after thalamotomy for prediction of symptomatic improvement at 1-year follow-up is 0.54.


TcMRgFUS thalamotomy results in significant decrease of rFA in the targeted VIM, at both 1 day and 1 year after treatment. Relative FA values at 1 day after treatment showed significant correlation with CRST score at 1-year follow-up. Therefore, FA may be considered a possible imaging biomarker for early prediction of clinical outcome after TcMRgFUS thalamotomy for essential tremor.

ABBREVIATIONS AC-PC = anterior commissure–posterior commissure; AUC = area under the curve; CRST = Clinical Rating Scale for Tremor; DTI = diffusion tensor imaging; FA = fractional anisotropy; FOV = field of view; rFA = relative FA; ROC = receiver operating characteristic; ROI = region of interest; SDR = skull density ratio; TcMRgFUS = transcranial MR-guided focused ultrasound; VIM = ventral intermediate nucleus.

Article Information

Correspondence Yoshihiro Muragaki: Institute of Advanced Biomedical Engineering and Science, Tokyo Women’s Medical University, Tokyo, Japan.

INCLUDE WHEN CITING Published online February 15, 2019; DOI: 10.3171/2018.10.JNS18993.

Disclosures The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.

© AANS, except where prohibited by US copyright law.



  • View in gallery

    Location of the ROI for posttreatment FA measurements in the VIM of both thalami using axial isotropic DTI (A) and a color-coded vector map (B) at the level of the AC-PC line. Of note, ROI was set at the presumed VIM in vicinity to the pyramidal tract (PT), but not at the thalamotomy lesion itself. Figure is available in color online only.

  • View in gallery

    Graph of dynamic changes in rFA in the targeted VIM after TcMRgFUS thalamotomy in cases with clinical improvement (circles) and recurrence of tremor (squares) at 1 year after treatment. Horizontal bars indicate median values for each group.

  • View in gallery

    Correlation between rFA values in the targeted VIM at 1 day after TcMRgFUS thalamotomy, and CRST improvement ratio at 1 year after treatment. Dashed line defines the cutoff value of 0.54 suggested by ROC analysis for prediction of good and durable symptomatic relief. Cases with clinical improvement (circles) and recurrence of tremor (squares) at 1-year follow-up are shown.



Akram HDayal VMahlknecht PGeorgiev DHyam JFoltynie T: Connectivity derived thalamic segmentation in deep brain stimulation for tremor. Neuroimage Clin 18:1301422018


Alexander ALLee JELazar MField AS: Diffusion tensor imaging of the brain. Neurotherapeutics 4:3163292007


Bland JMAltman DG: Statistical methods for assessing agreement between two methods of clinical measurement. Lancet 1:3073101986


Bond AEElias WJ: Predicting lesion size during focused ultrasound thalamotomy: a review of 63 lesions over 3 clinical trials. Neurosurg Focus 44(2):E52018


Chazen JLSarva HStieg PEMin RJBallon DJPryor KO: Clinical improvement associated with targeted interruption of the cerebellothalamic tract following MR-guided focused ultrasound for essential tremor. J Neurosurg 129:3153232018


Coenen VAAllert NMädler B: A role of diffusion tensor imaging fiber tracking in deep brain stimulation surgery: DBS of the dentato-rubro-thalamic tract (drt) for the treatment of therapy-refractory tremor. Acta Neurochir (Wien) 153:157915852011


Coenen VAJenkner CHoney CRMädler B: Electrophysiologic validation of diffusion tensor imaging tractography during deep brain stimulation surgery. AJNR Am J Neuroradiol 37:147014782016


Elias WJHuss DVoss TLoomba JKhaled MZadicario E: A pilot study of focused ultrasound thalamotomy for essential tremor. N Engl J Med 369:6406482013


Elias WJLipsman NOndo WGGhanouni PKim YGLee W: A randomized trial of focused ultrasound thalamotomy for essential tremor. N Engl J Med 375:7307392016


Fahn STolosa EMarin C: Clinical rating scale for tremor in Jankovic JTolosa E (eds): Parkinson’s Disease and Movement Disordersed 2. Baltimore: Williams & Wilkins1993 pp 271280


Federau CGoubran MRosenberg JHenderson JHalpern CHSantini V: Transcranial MRI-guided high-intensity focused ultrasound for treatment of essential tremor: a pilot study on the correlation between lesion size, lesion location, thermal dose, and clinical outcome. J Magn Reson Imaging 48:58652018


Gallay MNJeanmonod DLiu JMorel A: Human pallidothalamic and cerebellothalamic tracts: anatomical basis for functional stereotactic neurosurgery. Brain Struct Funct 212:4434632008


Gallay MNMoser DRossi FPourtehrani PMagara AEKowalski M: Incisionless transcranial MR-guided focused ultrasound in essential tremor: cerebellothalamic tractotomy. J Ther Ultrasound 4:52016


Jia LJia-Lin SQin DQing LYan Z: A diffusion tensor imaging study in essential tremor. J Neuroimaging 21:3703742011


Kiss ZHWilkinson MKrcek JSuchowersky OHu BMurphy WF: Is the target for thalamic deep brain stimulation the same as for thalamotomy? Mov Disord 18:116911752003


Klein JCLorenz BKang JSBaudrexel SSeifried Cvan de Loo S: Diffusion tensor imaging of white matter involvement in essential tremor. Hum Brain Mapp 32:8969042011


Krishna VSammartino FAgrawal PChangizi BKBourekas EKnopp MV: Prospective tractography-based targeting for improved safety of focused ultrasound thalamotomy. Neurosurgery 84:1601682019


Lefranc MCarron RRegis J: Prelemniscal radiations: a new reliable landmark of the thalamic nucleus ventralis intermedius location. Stereotact Funct Neurosurg 93:4004062015


Lipsman NSchwartz MLHuang YLee LSankar TChapman M: MR-guided focused ultrasound thalamotomy for essential tremor: a proof-of-concept study. Lancet Neurol 12:4624682013


Maeda T: Lateral coordinates of nucleus ventralis intermedius target for tremor alleviation. Stereotact Funct Neurosurg 52:1911991989


Martin EJeanmonod DMorel AZadicario EWerner B: High-intensity focused ultrasound for noninvasive functional neurosurgery. Ann Neurol 66:8588612009


Mori SCrain BJChacko VPvan Zijl PC: Three-dimensional tracking of axonal projections in the brain by magnetic resonance imaging. Ann Neurol 45:2652691999


Mori SZhang J: Principles of diffusion tensor imaging and its applications to basic neuroscience research. Neuron 51:5275392006


Ohye C: From selective thalamotomy with microrecording to gamma thalamotomy for movement disorders. Stereotact Funct Neurosurg 84:1551612006


Ohye CHiguchi YShibazaki THashimoto TKoyama THirai T: Gamma knife thalamotomy for Parkinson disease and essential tremor: a prospective multicenter study. Neurosurgery 70:5265362012


Rezai ARMachado AGDeogaonkar MAzmi HKubu CBoulis NM: Surgery for movement disorders. Neurosurgery 62 (2 Suppl 2):8098392008


Saini JBagepally BSBhatt MDChandran VBharath RDPrasad C: Diffusion tensor imaging: tract based spatial statistics study in essential tremor. Parkinsonism Relat Disord 18:4774822012


Sammartino FKrishna VKing NKLozano AMSchwartz MLHuang Y: Tractography-based ventral intermediate nucleus targeting: novel methodology and intraoperative validation. Mov Disord 31:121712252016


Sato SOhye CShibazaki TZama ACai X: Neurophysiological evaluation of the optimum target in gamma thalamotomy: indirect evidence. Stereotact Funct Neurosurg 83:1081142005


Shin DHHan BSKim HSLee PH: Diffusion tensor imaging in patients with essential tremor. AJNR Am J Neuroradiol 29:1511532008


Stacy MAElble RJOndo WGWu SCHulihan J: Assessment of interrater and intrarater reliability of the Fahn-Tolosa-Marin Tremor Rating Scale in essential tremor. Mov Disord 22:8338382007


Wintermark MHuss DSShah BBTustison NDruzgal TJKassell N: Thalamic connectivity in patients with essential tremor treated with MR imaging-guided focused ultrasound: in vivo fiber tracking by using diffusion-tensor MR imaging. Radiology 272:2022092014


Yagishita ANakano IOda MHirano A: Location of the corticospinal tract in the internal capsule at MR imaging. Radiology 191:4554601994


Yamada KAkazawa KYuen SGoto MMatsushima STakahata A: MR imaging of ventral thalamic nuclei. AJNR Am J Neuroradiol 31:7327352010


Yamada KKizu OKubota TIto HMatsushima SOouchi H: The pyramidal tract has a predictable course through the centrum semiovale: a diffusion-tensor based tractography study. J Magn Reson Imaging 26:5195242007


Zarei MJohansen-Berg HJenkinson MCiccarelli OThompson AJMatthews PM: Two-dimensional population map of cortical connections in the human internal capsule. J Magn Reson Imaging 25:48542007




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