Impact of skull density ratio on efficacy and safety of magnetic resonance–guided focused ultrasound treatment of essential tremor

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OBJECTIVE

Skull density ratio (SDR) assesses the transparency of the skull to ultrasound. Magnetic resonance–guided focused ultrasound (MRgFUS) thalamotomy in essential tremor (ET) patients with a lower SDR may be less effective, and the risk for complications may be increased. To address these questions, the authors analyzed clinical outcomes of MRgFUS thalamotomy based on SDRs.

METHODS

In 189 patients, 3 outcomes were correlated with SDRs. Efficacy was based on improvement in Clinical Rating Scale for Tremor (CRST) scores 1 year after MRgFUS. Procedural efficiency was determined by the ease of achieving a peak voxel temperature of 54°C. Safety was based on the rate of the most severe procedure-related adverse event. SDRs were categorized at thresholds of 0.45 and 0.40, selected based on published criteria.

RESULTS

Of 189 patients, 53 (28%) had an SDR < 0.45 and 20 (11%) had an SDR < 0.40. There was no significant difference in improvement in CRST scores between those with an SDR ≥ 0.45 (58% ± 24%), 0.40 ≤ SDR < 0.45 (i.e., SDR ≥ 0.40 but < 0.45) (63% ± 27%), and SDR < 0.40 (49% ± 28%; p = 0.0744). Target temperature was achieved more often in those with an SDR ≥ 0.45 (p < 0.001). Rates of adverse events were lower in the groups with an SDR < 0.45 (p = 0.013), with no severe adverse events in these groups.

CONCLUSIONS

MRgFUS treatment of ET can be effectively and safely performed in patients with an SDR < 0.45 and an SDR < 0.40, although the procedure is more efficient when SDR ≥ 0.45.

ABBREVIATIONS CRST = Clinical Rating Scale for Tremor; ET = essential tremor; FUS = focused ultrasound; MRgFUS = magnetic resonance–guided focused ultrasound; SDR = skull density ratio.

Article Information

Correspondence Pejman Ghanouni: Stanford University, Stanford, CA. ghanouni@stanford.edu.

INCLUDE WHEN CITING Published online April 26, 2019; DOI: 10.3171/2019.2.JNS183517.

C.H.H. and P.G. contributed equally to this work.

Disclosures InSightec provided research funding for clinical trials related to MRgFUS treatment of essential tremor. Drs. Ghanouni, Halpern, Henderson, Elias, Eisenberg, Gwinn, Taira, Chang, Lipsman, Krishna, Igase, Yamada, Kishima, Cosgrove, Rumià, Kaplitt, Hirabayashi, Eisenberg, and Nandi receive research funding from InSightec. Conduct of the study, data analysis and interpretation, and preparation and approval of the manuscript were done independently of InSightec. Initial design of the study was performed by Drs. Ghanouni, Halpern, and Dayan, who is an employee of InSightec. Data collection was performed by Dr. Dayan, who also reviewed the manuscript. Dr. Elias reports receiving support of non–study-related clinical or research efforts that he oversees from InSightec. Dr. Taira reports being a consultant for InSightec Japan. Dr. Lipsman reports having served as chair on the Expert Steering Committee of the Focused Ultrasound Foundation. Dr. Krishna reports receiving funding for a clinical trial from InSightec. Dr. Yamada reports receiving support for the study described from Hokuto Hospital. Dr. Cosgrove reports receiving research funding for clinical trials from InSightec. Dr. Halpern reports receiving speaking honoraria from Mazor Robotics and being a consultant for Medtronic. Dr. Ghanouni reports receiving support of non–study-related clinical or research efforts that he oversees from InSightec. Dr. Dayan is an employee of InSightec.

© AANS, except where prohibited by US copyright law.

Headings

Figures

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    SDR compared to change in CRST score. The percentage change in CRST score at 12 months after MRgFUS did not correlate with the SDR (blue line, r2 = 0.0098; < 1% of the variance in CRST score can be explained by variance in the SDR). Improvement of 50% in CRST scores is marked on the graph (dotted line). Figure is available in color online only.

  • View in gallery

    SDR distribution of 189 patients with ET treated with MRgFUS. Each bar represents the percentage of patients of the cohort within each SDR interval, with each interval representing SDRs less than the higher number in the range. The mean SDR value was 0.52 ± 0.11 (± SD). SDRs ranged from 0.27 to 0.82. Out of 189 patients, 53 (28%) had an SDR < 0.45 and 20 (11%) had an SDR < 0.40. Figure is available in color online only.

  • View in gallery

    Cumulative percent improvement in CRST scores at 1 year after MRgFUS for patients based on SDR categories. For patients with an SDR ≥ 0.45 (green line), 68% demonstrated at least a 50% improvement in CRST score at the 1-year follow-up (n = 136; the mean percentage improvement in CRST score was 58% ± 24%). For patients with 0.40 ≤ SDR < 0.45 (red line), 79% demonstrated at least a 50% improvement in CRST score at the 1-year follow-up (n = 33; the mean percentage improvement in CRST was 63% ± 27%). For patients with an SDR < 0.40 (blue line), 50% demonstrated at least a 50% improvement in CRST score at the 1-year follow-up (n = 20; the mean percentage improvement in CRST score was 49% ± 28%). The dashed line intersects each curve at the point where patients have at least a 50% improvement in CRST scores 1 year after MRgFUS. The threshold value of 50% improvement was chosen based on previous publications reporting the average results of MRgFUS treatment in patients with ET.5,7 Figure is available in color online only.

References

  • 1

    Abe KTaira T: Focused ultrasound treatment, present and future. Neurol Med Chir (Tokyo) 57:3863912017

  • 2

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

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 3

    Boutet ARanjan MZhong JGermann JXu DSchwartz ML: Focused ultrasound thalamotomy location determines clinical benefits in patients with essential tremor. Brain 141:340534142018

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4

    Butts Pauly KFederau CWerner BHalpern CGhanouni P: Inflection of temperature vs. power curve in tcMRgFUS: correlation with lesion location. J Therapeutic Ultrasound 4 (Suppl 1):A192016 (Abstract A19)

    • Search Google Scholar
    • Export Citation
  • 5

    Chang JWPark CKLipsman NSchwartz MLGhanouni PHenderson JM: A prospective trial of magnetic resonance-guided focused ultrasound thalamotomy for essential tremor: results at the 2-year follow-up. Ann Neurol 83:1071142018

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6

    Chang WSJung HHZadicario ERachmilevitch ITlusty TVitek S: Factors associated with successful magnetic resonance-guided focused ultrasound treatment: efficiency of acoustic energy delivery through the skull. J Neurosurg 124:4114162016

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7

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

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8

    Fishman PSElias WJGhanouni PGwinn RLipsman NSchwartz M: Neurological adverse event profile of magnetic resonance imaging-guided focused ultrasound thalamotomy for essential tremor. Mov Disord 33:8438472018

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 9

    Hughes AHuang YSchwartz MLHynynen K: The reduction in treatment efficiency at high acoustic powers during MR-guided transcranial focused ultrasound thalamotomy for essential tremor. Med Phys 45:292529362018

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10

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

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11

    Laitinen LV: Brain targets in surgery for Parkinson’s disease. Results of a survey of neurosurgeons. J Neurosurg 62:3493511985

  • 12

    Ravikumar VKParker JJHornbeck TSSantini VEPauly KBWintermark M: Cost-effectiveness of focused ultrasound, radiosurgery, and DBS for essential tremor. Mov Disord 32:116511732017

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13

    Sammartino FBeam DWSnell JKrishna V: Kranion, an open-source environment for planning transcranial focused ultrasound surgery: technical note. J Neurosurg [epub ahead of print March 1 2019. DOI: 10.3171/2018.11.JNS181995]

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 14

    Schwartz MLYeung RHuang YLipsman NKrishna VJain JD: Skull bone marrow injury caused by MR-guided focused ultrasound for cerebral functional procedures. J Neurosurg 130:7587622019

    • Search Google Scholar
    • Export Citation
  • 15

    Vyas UGhanouni PHalpern CHElias JPauly KB: Predicting variation in subject thermal response during transcranial magnetic resonance guided focused ultrasound surgery: comparison in seventeen subject datasets. Med Phys 43:517051802016

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16

    Wang TRBond AEDallapiazza RFBlanke ATilden DHuerta TE: Transcranial magnetic resonance imaging-guided focused ultrasound thalamotomy for tremor: technical note. Neurosurg Focus 44(2):E32018

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 17

    Webb TDLeung SARosenberg JGhanouni PDahl JJPelc NJ: Measurements of the relationship between CT Hounsfield units and acoustic velocity and how it changes with photon energy and reconstruction method. IEEE Trans Ultrason Ferroelectr Freq Control 65:111111242018

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 18

    Zesiewicz TAChari AJahan IMiller AMSullivan KL: Overview of essential tremor. Neuropsychiatr Dis Treat 6:4014082010

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