Ryan M. Jones, Shona Kamps, Yuexi Huang, Nadia Scantlebury, Nir Lipsman, Michael L. Schwartz and Kullervo Hynynen
The object of this study was to correlate lesion size with accumulated thermal dose (ATD) in transcranial MRI-guided focused ultrasound (MRgFUS) treatments of essential tremor with focal temperatures limited to 50°C–54°C.
Seventy-five patients with medically refractory essential tremor underwent MRgFUS thalamotomy at the authors’ institution. Intraoperative MR thermometry was performed to measure the induced temperature and thermal dose distributions (proton resonance frequency shift coefficient = −0.00909 ppm/°C). In 19 patients, it was not possible to raise the focal temperature above 54°C because of unfavorable skull characteristics and/or the pain associated with cranial heating. In this patient subset, sonications with focal temperatures between 50°C and 54°C were repeated (5.1 ± 1.5, mean ± standard deviation) to accumulate a sufficient thermal dose for lesion formation. The ATD profile sizes (17, 40, 100, 200, and 240 cumulative equivalent minutes at 43°C [CEM43]) calculated by combining axial MR thermometry data from individual sonications were correlated with the corresponding lesion sizes measured on axial T1-weighted (T1w) and T2-weighted (T2w) MR images acquired 1 day posttreatment. Manual corrections were applied to the MR thermometry data prior to thermal dose accumulation to compensate for off-resonance–induced spatial-shifting artifacts.
Mean lesion sizes measured on T2w MRI (5.0 ± 1.4 mm) were, on average, 28% larger than those measured on T1w MRI (3.9 ± 1.4 mm). The ATD thresholds found to provide the best correlation with lesion sizes measured on T2w and T1w MRI were 100 CEM43 (regression slope = 0.97, R2 = 0.66) and 200 CEM43 (regression slope = 0.98, R2 = 0.89), respectively, consistent with data from a previous study of MRgFUS thalamotomy via repeated sonications at higher focal temperatures (≥ 55°C). Two-way linear mixed-effects analysis revealed that dominant tremor subscores on the Fahn-Tolosa-Marin Clinical Rating Scale for Tremor (CRST) were statistically different from baseline at 3 months and 1 year posttreatment in both low-temperature (50°C–54°C) and high-temperature (≥ 55°C) patient cohorts. No significant fixed effect on the dominant tremor scores was found for the temperature cohort factor.
In transcranial MRgFUS thalamotomy for essential tremor, repeated sonications with focal temperatures between 50°C and 54°C can accumulate a sufficient thermal dose to generate lesions for clinically relevant tremor suppression up to 1 year posttreatment, and the ATD can be used to predict the size of the resulting ablation zones measured on MRI. These data will serve to guide future clinical MRgFUS brain procedures, particularly those in which focal temperatures are limited to below 55°C.
Ying Meng, Christopher B. Pople, Suneil K. Kalia, Lorraine V. Kalia, Benjamin Davidson, Luca Bigioni, Daniel Zhengze Li, Suganth Suppiah, Karim Mithani, Nadia Scantlebury, Michael L. Schwartz, Clement Hamani and Nir Lipsman
The development of transcranial MR-guided focused ultrasound (MRgFUS) has revitalized the practice of lesioning procedures in functional neurosurgery. Previous health economic analysis found MRgFUS thalamotomy to be a cost-effective treatment for patients with essential tremor, supporting its reimbursement. With the publication of level I evidence in support of MRgFUS thalamotomy for patients with tremor-dominant Parkinson’s disease (TDPD), the authors performed a health economic comparison between MRgFUS, deep brain stimulation (DBS), and medical therapy.
The authors used a decision tree model with rollback analysis and one-factor sensitivity analysis. Literature searches of MRgFUS thalamotomy and unilateral DBS of the ventrointermediate nucleus of the thalamus for TDPD were performed to determine the utility and probabilities for the model. Costs in Canadian dollars (CAD) were derived from the Schedule of Benefits and Fees in Ontario, Canada, and expert opinion on usage.
MRgFUS was associated with an expected cost of $14,831 CAD. Adding MRgFUS to continued medical therapy resulted in an incremental cost-effectiveness ratio of $30,078 per quality-adjusted life year (QALY), which remained cost-effective under various scenarios in the sensitivity analysis. Comparing DBS to MRgFUS, while DBS did not achieve the willingness-to-pay threshold ($56,503 per QALY) in the base case scenario, it did so under several scenarios in the sensitivity analysis.
MRgFUS thalamotomy is a cost-effective treatment for patients with TDPD, particularly over continued medical therapy. While MRgFUS remains competitive with DBS, the cost-effectiveness advantage is less substantial. These results will help inform the integration of this technology in the healthcare system.
Iska Moxon-Emre, Eric Bouffet, Michael D. Taylor, Normand Laperriere, Michael B. Sharpe, Suzanne Laughlin, Ute Bartels, Nadia Scantlebury, Nicole Law, David Malkin, Jovanka Skocic, Logan Richard and Donald J. Mabbott
Craniospinal irradiation damages the white matter in children treated for medulloblastoma, but the treatment-intensity effects are unclear. In a cross-sectional retrospective study, the effects of treatment with the least intensive radiation protocol versus protocols that delivered more radiation to the brain, in addition to the effects of continuous radiation dose, on white matter architecture were evaluated.
Diffusion tensor imaging was used to assess fractional anisotropy, mean diffusivity, radial diffusivity, and axial diffusivity. First, regional white matter analyses and tract-based spatial statistics were conducted in 34 medulloblastoma patients and 38 healthy controls. Patients were stratified according to those treated with 1) the least intensive radiation protocol, specifically reduced-dose craniospinal irradiation plus a boost to the tumor bed only (n = 17), or 2) any other dose and boost combination that delivered more radiation to the brain, which was also termed the “all-other-treatments” group (n = 17), and comprised patients treated with standard-dose craniospinal irradiation plus a posterior fossa boost, standard-dose craniospinal irradiation plus a tumor bed boost, or reduced-dose craniospinal irradiation plus a posterior fossa boost. Second, voxel-wise dose-distribution analyses were conducted on a separate cohort of medulloblastoma patients (n = 15).
The all-other-treatments group, but not the reduced-dose craniospinal irradiation plus tumor bed group, had lower fractional anisotropy and higher radial diffusivity than controls in all brain regions (all p < 0.05). The reduced-dose craniospinal irradiation plus tumor bed boost group had higher fractional anisotropy (p = 0.05) and lower radial diffusivity (p = 0.04) in the temporal region, and higher fractional anisotropy in the frontal region (p = 0.04), than the all-other-treatments group. Linear mixed-effects modeling revealed that the dose and age at diagnosis together 1) better predicted fractional anisotropy in the temporal region than models with either alone (p < 0.005), but 2) did not better predict fractional anisotropy in comparison with dose alone in the occipital region (p > 0.05).
Together, the results show that white matter damage has a clear association with increasing radiation dose, and that treatment with reduced-dose craniospinal irradiation plus tumor bed boost appears to preserve white matter in some brain regions.