Minimum and early high-energy sonication protocol of MR-guided focused ultrasound thalamotomy for low-skull density ratio patients with essential tremor and Parkinson's disease.

OBJECTIVE: MR-guided focused ultrasound (MRgFUS) thalamotomy is an incisionless neurosurgical treatment for patients with medically refractory essential tremor and tremor-dominant Parkinson's disease. A low skull density ratio (SDR) < 0.40 is a known risk factor for treatment failure. The aim of this study was to identify useful sonication strategies for patients with a low SDR < 0.40 by modifying the standard sonication protocol using maximum high-energy sonication while minimizing the number of sonications. METHODS: The authors retrospectively analyzed the effects of modified MRgFUS sonication on low-SDR tremor patients. All patients underwent head CT scans to calculate their SDR. The SDR threshold for MRgFUS thalamotomy was 0.35. The patients in the early series underwent the standard sonication protocol targeting the ventral intermediate nucleus contralateral to the treated hand side. The patients with a low SDR < 0.40 in the late series underwent a modified sonication protocol, in which the number of alignment sonications was minimized and high-energy treatment sonication (> 36,000 J) was used. The authors evaluated the lesion volume the following day and tremor improvement and adverse events 3 and 12 months after the procedure. The sonication patterns between low-SDR patients treated using different sonication protocols were examined using Fisher's exact test. ANOVA was used to examine the lesion volume and tremor improvement in high- and low-SDR patients treated using different sonication protocols. RESULTS: Among 41 patients with an SDR < 0.40, 14 underwent standard sonication and 27 underwent modified sonication. Fewer alignment sonications and high-energy treatment sonications were used in the modified sonication group compared with the standard group (p < 0.001). The duration of modified sonication was significantly shorter than that of standard sonication (p < 0.001). The lesion volume and tremor improvement significantly differed among the high- and low-SDR groups with different sonication protocols (p < 0.001). Low-SDR patients treated using modified sonication protocols had comparable lesion volume and tremor improvement to the high-SDR group. The modified sonication protocol did not significantly increase adverse intraprocedural and postprocedural events. CONCLUSIONS: Minimizing alignment sonications and applying high-energy sonication in early treatment help to create an optimal lesion volume and control tremor in low-SDR patients.

Magnetic resonance-guided focused ultrasound thalamotomy for essential tremor patients with low skull density ratio: a case-matched analysis.

Introduction: Skull density ratio (SDR) is the ratio between the mean Hounsfield units of marrow and cortical bone, impacting energy transmission through the skull. Low SDR has been used as an exclusion criterion in major trials of magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy for medication-refractory essential tremor (ET). However, some studies have suggested that patients with low SDR can safely undergo MRgFUS with favorable outcomes. In this case-matched study, we aim to compare the characteristics, sonication parameters, lesion sizes, and clinical outcomes of patients with low SDR vs. patients with high SDR who underwent unilateral MRgFUS thalamotomy for medication-refractory ET. Methods: Between March 2016 and April 2023, all patients (n = 270) who underwent unilateral MRgFUS thalamotomy for medication-refractory ET at a single institution were classified as low SDR (<0.40) and high SDR (≥0.40). All clinical and radiological data was prospectively collected and retrospectively analyzed using non-case-matched and 1:1 case-matched methodology. Results: Thirty-one patients had low SDR, and 239 patients had high SDR. Fifty-six patients (28 in each cohort) were included in 1:1 case-matched analysis. There were no significant differences in baseline characteristics between the two groups in both non-case-matched and 1:1 case-matched analyses. In both analyses, compared to patients with high SDR, patients with low SDR required a significantly higher maximum sonication power, energy, and duration, and reached a lower maximum temperature with smaller lesion volumes. In the non-case-matched and case-matched analyses, low SDR patients did not have significantly less tremor control at any postoperative timepoints. However, there was a higher chance of procedure failure in the low SDR group with three patients not obtaining an appropriately sized lesion. In both analyses, imbalance was observed more often in high SDR patients on postoperative day 1 and month 3. Discussion: ET patients with SDR <0.40 can be safely and effectively treated with MRgFUS, though there may be higher rates of treatment failure and intraoperative discomfort.

Skull Density Ratio as Arm-Allocation Parameter for a Controlled Focused Ultrasound Trial in Parkinson's Disease.

BACKGROUND: MR-guided focused ultrasound (FUS) thermoablation is an established therapy for movement disorders. FUS candidates must meet a predefined threshold of skull density ratio (SDR), a parameter that accounts for the efficiency in reaching ablative temperatures. Randomized sham-controlled trials to provide definitive therapeutic evidence employ pure randomization of subjects into active treatment or control arms. The latter design has several general limitations. OBJECTIVE: To demonstrate that SDR values are not associated with clinically and demographically relevant variables in patients with Parkinson's disease (PD). This in turn would allow using SDR as an arm-allocation parameter, separating patients who will receive active FUS treatment and best medical management treatment (BMT). METHODS: We studied a cohort of 215 PD patients who were candidates for FUS subthalamotomy to determine if the SDR was correlated with demographic or clinical variables that could introduce bias for group allocation in a controlled trial. RESULTS: SDR was unassociated with age, gender, and clinical motor features nor with levodopa daily dose in our cohort of PD patients. A negative association with age was found for the female subgroup. CONCLUSIONS: Our results show that in a PD population considered for FUS subthalamotomy treatment, the SDR may be a valid group-allocation parameter. This could be considered as the basis for a controlled study comparing FUS subthalamotomy vs BMT.

Effectiveness and safety of MR-guided focused ultrasound thalamotomy in patients with essential tremor and low skull density ratio: a study of 101 cases.

OBJECTIVE: The objective was to investigate the effectiveness and safety of MR-guided focused ultrasound (MRgFUS) treatment in patients with essential tremor, particularly those with low skull density ratio (SDR) and including those with very low SDR, and to identify the factors influencing treatment effectiveness and to provide insights into therapeutic approaches for patients with lower SDR. METHODS: Real-world data from 101 patients who underwent MRgFUS between July 2019 and March 2022 at a single institution were analyzed. Tremor severity was assessed using the Fahn-Tolosa-Marin Clinical Rating Scale for Tremor (CRST). The patients were categorized into quartile groups based on their mean SDR, and the characteristics, treatment effectiveness, treatment parameters, and adverse events were evaluated among these subgroups. RESULTS: Patients were classified into 4 quartiles based on the mean SDR: quartile 1 (Q1) (SDR 0.26-0.37), Q2 (SDR 0.38-0.42), Q3 (SDR 0.43-0.49), and Q4 (SDR 0.50-0.75). MRgFUS significantly improved total CRST and tremor score across all SDR subgroups. Additionally, there were no significant differences in the improvement rates among the 4 subgroups. Analysis of the treatment parameters revealed that lower mean SDR was associated with lower target maximum temperature and smaller coagulation volume after focused ultrasound (FUS). Regarding adverse events, headache and nausea during FUS and facial and head edema on the day after surgery were more frequent in the Q1 subgroup (very low-SDR group). In contrast, numbness was more common in the Q4 subgroup. However, all these adverse events had resolved by the 3-month follow-up except numbness. CONCLUSIONS: This study suggested that MRgFUS is effective and safe for patients with medication-resistant essential tremor, including those with very low mean SDR. However, the very low-SDR group had insufficient temperature elevation at the target site compared with the high-SDR group, suggesting the need for a different strategy. Notably, with careful adjustments and considerations, positive outcomes can still be achieved in patients with very low SDR. Therefore, very low SDR should not be considered an absolute exclusion criterion because it is expected to increase the number of patients who benefit from MRgFUS.

Consistency is key: influence of skull density ratio distribution on the formation of clinically effective lesions and long-term tremor suppression following treatment with MR-guided focused ultrasound.

OBJECTIVE: Skull density ratio (SDR) influences the permeability of the skull to the ultrasound waves used in magnetic resonance-guided focused ultrasound (MRgFUS) for the treatment of tremor. SDR values vary across the skull and the mean value is known to be predictive of sonication thermal increase. The aim of this investigation was to explore the effects of the SDR distribution on clinical outcomes following treatment with MRgFUS. METHODS: Data from 61 patients with essential or dystonic tremor treated with MRgFUS targeting the ventral intermediate nucleus (Vim) were retrospectively analyzed. Tremor suppression was assessed using the Clinical Rating Scale for Tremor (CRST) and hand tremor score (HTS). Vim ablation volume was measured on the T1-weighted MR image acquired both at 1 day and 12 months after treatment. The numerical distribution of SDR values measured for each element in the ultrasound transducer was quantified by calculating the mean, standard deviation, skewness, entropy, and kurtosis of the SDR histogram. The effect of the SDR metrics on change in CRST and HTS was examined using a linear mixed-effects model. Additionally, the effect of the regional distribution of SDR values was explored in an element-wise analysis between patients with above- and below-average tremor suppression. RESULTS: A significant positive effect was found between SDR kurtosis and improvement in CRST (ß = 0.33, p = 0.004) and HTS (ß = 0.38, p < 0.001). The effect was found to be significant at 1 month posttreatment (CRST: ß = 0.415, p = 0.008; HTS: ß = 0.369, p = 0.016), and at the most recent clinical follow-up (CRST: ß = 0.395, p < 0.001; HTS: ß = 0.386, p < 0.001). One hundred seventy-one significant elements were identified in the element-wise analysis. The mean percentage difference from the mean SDR in these elements was associated with improvement in CRST (ß = 0.27, p < 0.008) and HTS (ß = 0.27, p < 0.015). Higher SDR kurtosis was associated with increased lesion volume at 12 months (p = 0.040) and less reduction in volume relative to the day-1 lesion volume (p = 0.007). CONCLUSIONS: Greater SDR kurtosis was associated with larger, more stable lesions at 12 months posttreatment and increased tremor suppression at long-term follow-up. SDR kurtosis may provide a more meaningful prognostic factor than the mean SDR.

Successful magnetic resonance-guided focused ultrasound treatment of tremor in patients with a skull density ratio of 0.4 or less.

OBJECTIVE: The use of magnetic resonance-guided focused ultrasound (MRgFUS) for the treatment of tremor-related disorders and other novel indications has been limited by guidelines advocating treatment of patients with a skull density ratio (SDR) above 0.45 ± 0.05 despite reports of successful outcomes in patients with a low SDR (LSDR). The authors' goal was to retrospectively analyze the sonication strategies, adverse effects, and clinical and imaging outcomes in patients with SDR ≤ 0.4 treated for tremor using MRgFUS. METHODS: Clinical outcomes and adverse effects were assessed at 3 and 12 months after MRgFUS. Outcomes and lesion location, volume, and shape characteristics (elongation and eccentricity) were compared between the SDR groups. RESULTS: A total of 102 consecutive patients were included in the analysis, of whom 39 had SDRs ≤ 0.4. No patient was excluded from treatment because of an LSDR, with the lowest being 0.22. Lesioning temperatures (> 52°C) and therapeutic ablations were achieved in all patients. There were no significant differences in clinical outcome, adverse effects, lesion location, and volume between the high SDR group and the LSDR group. SDR was significantly associated with total energy (rho = -0.459, p < 0.001), heating efficiency (rho = 0.605, p < 0.001), and peak temperature (rho = 0.222, p = 0.025). CONCLUSIONS: The authors' results show that treatment of tremor in patients with an LSDR using MRgFUS is technically possible, leading to a safe and lasting therapeutic effect. Limiting the number of sonications and adjusting the energy and duration to achieve the required temperature early during the treatment are suitable strategies in LSDR patients.

Comparison of the impact of skull density ratio with alternative skull metrics on magnetic resonance-guided focused ultrasound thalamotomy for tremor.

OBJECTIVE: One of the key metrics that is used to predict the likelihood of success of MR-guided focused ultrasound (MRgFUS) thalamotomy is the overall calvarial skull density ratio (SDR). However, this measure does not fully predict the sonication parameters that would be required or the technical success rates. The authors aimed to assess other skull characteristics that may also contribute to technical success. METHODS: The authors retrospectively studied consecutive patients with essential tremor who were treated by MRgFUS at their center between 2017 and 2021. They evaluated the correlation between the different treatment parameters, particularly maximum power and energy delivered, with a range of patients' skull metrics and demographics. Machine learning algorithms were applied to investigate whether sonication parameters could be predicted from skull density metrics alone and whether including combined local transducer SDRs with overall calvarial SDR would increase model accuracy. RESULTS: A total of 62 patients were included in the study. The mean age was 77.1 (SD 9.2) years, and 78% of treatments (49/63) were performed in males. The mean SDR was 0.51 (SD 0.10). Among the evaluated metrics, SDR had the highest correlation with the maximum power used in treatment (ρ = -0.626, p < 0.001; proportion of local SDR values ≤ 0.8 group also had ρ = +0.626, p < 0.001) and maximum energy delivered (ρ = -0.680, p < 0.001). Machine learning algorithms achieved a moderate ability to predict maximum power and energy required from the local and overall SDRs (accuracy of approximately 80% for maximum power and approximately 55% for maximum energy), and high ability to predict average maximum temperature reached from the local and overall SDRs (approximately 95% accuracy). CONCLUSIONS: The authors compared a number of skull metrics against SDR and showed that SDR was one of the best indicators of treatment parameters when used alone. In addition, a number of other machine learning algorithms are proposed that may be explored to improve its accuracy when additional data are obtained. Additional metrics related to eventual sonication parameters should also be identified and explored.

Transcranial MR-Guided Focused Ultrasound and Hyperostosis Calvariae Diffusa: Case Report and Systematic Review of the Literature.

We describe a 74-year-old male with intractable essential tremor (ET) and hyperostosis calvariae diffusa who was unsuccessfully treated with magnetic resonance-guided focused ultrasound (MRgFUS). A computed tomography performed prior to the procedure demonstrated a skull density ratio (SDR) of 0.37 and tricortical hyperostosis calvariae diffusa. No lesion was evident on post-MRgFUS MRI, and no improvement in the patient's hand tremor was noted clinically. We systematically reviewed the literature to understand outcomes for those patients with hyperostosis who have undergone MRgFUS. A comprehensive literature search using the PubMed, Cochrane, and Google Scholar databases identified 3 ET patients with hyperostosis who failed treatment with MRgFUS. Clinical findings, skull characteristics, treatment parameters, and outcomes were summarized, demonstrating different patterns/degrees of bicortical hyperostosis and variable SDRs (i.e., from 0.38 to ≥0.45). Although we have successfully treated patients with bicortical hyperostosis frontalis interna (n = 50), tricortical hyperostosis calvariae diffusa appears to be a contraindication for MRgFUS despite acceptable SDRs.

Hyperostosis in Combination With Low Skull Density Ratio: A Potential Contraindication for Magnetic Resonance Imaging-Guided Focused Ultrasound Thalamotomy.

Since its approval in treating a number of movement disorders, magnetic resonance imaging-guided focused ultrasound (MRgFUS) has been adopted rapidly as one of the standard treatment modalities internationally. However, the efficiency of the energy delivered by the ultrasonic waves is largely determined by the highly variable bone morphology and density characteristics of the skull. One of the widely accepted indices used to facilitate patient selection is the skull density ratio (SDR). Earlier literature suggested that an SDR of less than 0.4 would be unfavorable for MRgFUS treatment. Some prior studies have excluded patients with hyperostosis. However, there is little published data regarding the impact of other skull features such as hyperostosis on treatment success. We present the case of a 66-year-old man with medically refractory essential tremor who had an SDR of 0.38 and extensive hyperostosis frontalis interna and underwent attempted MRgFUS thalamotomy treatment. However, intraoperatively the treatment was unsuccessful in generating sufficiently elevated temperature to create a lesion of the usual desired volume, and as expected, there was minimal clinical improvement. For comparison, we also summarize a case series of 4 other patients with an SDR of less than 0.4 who had successful outcomes. We believe that SDR should not be used as the only means of selecting patients for MRgFUS. Instead, important factors such as hyperostosis should be taken into consideration for patient selection and pretreatment counseling.

Predictors of thermal increase in magnetic resonance-guided focused ultrasound treatment for essential tremor: histogram analysis of skull density ratio values for 1024 elements.

OBJECTIVE: Sufficient thermal increase capable of generating thermocoagulation is indispensable for an effective clinical outcome in patients undergoing magnetic resonance-guided focused ultrasound (MRgFUS). The skull density ratio (SDR) is one of the most dominant predictors of thermal increase prior to treatment. However, users currently rely only on the average SDR value (SDRmean) as a screening criterion, although some patients with low SDRmean values can achieve sufficient thermal increase. The present study aimed to examine the numerical distribution of SDR values across 1024 elements to identify more precise predictors of thermal increase during MRgFUS. METHODS: The authors retrospectively analyzed the correlations between the skull parameters and the maximum temperature achieved during unilateral ventral intermediate nucleus thalamotomy with MRgFUS in a cohort of 55 patients. In addition, the numerical distribution of SDR values was quantified across 1024 elements by using the skewness, kurtosis, entropy, and uniformity of the SDR histogram. Next, the authors evaluated the correlation between the aforementioned indices and a peak temperature > 55°C by using univariate and multivariate logistic regression analyses. Receiver operating characteristic curve analysis was performed to compare the predictive ability of the indices. The diagnostic performance of significant factors was also assessed. RESULTS: The SDR skewness (SDRskewness) was identified as a significant predictor of thermal increase in the univariate and multivariate logistic regression analyses (p < 0.001, p = 0.013). Moreover, the receiver operating characteristic curve analysis indicated that the SDRskewness exhibited a better predictive ability than the SDRmean, with area under the curve values of 0.847 and 0.784, respectively. CONCLUSIONS: The SDRskewness is a more accurate predictor of thermal increase than the conventional SDRmean. The authors suggest setting the SDRskewness cutoff value to 0.68. SDRskewness may allow for the inclusion of treatable patients with essential tremor who would have been screened out based on the SDRmean exclusion criterion.

Factors Associated with Energy Efficiency of Focused Ultrasound Through the Skull: A Study of 3D-Printed Skull Phantoms and Its Comparison with Clinical Experiences.

While focused ultrasound (FUS) is non-invasive, the ultrasound energy is attenuated by the skull which results in differences in energy efficiency among patients. In this study, we investigated the effect of skull variables on the energy efficiency of FUS. The thickness and density of the skull and proportion of the trabecular bone were selected as factors that could affect ultrasound energy transmittance. Sixteen 3D-printed skull models were designed and fabricated to reflect the three factors. The energy of each phantom was measured using an ultrasonic sound field energy measurement system. The thickness and proportion of trabecular bone affected the attenuation of transmitted energy. There was no difference in the density of the trabecular bone. In clinical data, the trabecular bone ratio showed a significantly greater correlation with dose/delivered energy than that of thickness and the skull density ratio. Currently, for clinical non-thermal FUS, the data are not sufficient, but we believe that the results of this study will be helpful in selecting patients and appropriate parameters for FUS treatment.

Patient-specific effects on sonication heating efficiency during magnetic resonance-guided focused ultrasound thalamotomy.

PURPOSE: During magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy for refractory tremor, high temperatures must be achieved and sustained for tissue necrosis. We assessed the impact of both patient-specific as well as procedure-related factors on the efficiency of acoustic energy transfer, or heating efficiency (HE). METHODS: Retrospective analysis of 92 consecutive patients (857 sonications) with essential tremor or tremor-dominant Parkinson's disease treated at a single institution. Temperature elevations at the target were measured for each sonication with MR thermometry. HE of each sonication was defined as the ratio of peak temperature elevation and the delivered energy. HE was analyzed with respect to patient skull features (area, thickness, skull density ratio [SDR]), computed from CT scans, as well as demographic and clinical variables (age, sex, diagnosis, and duration of symptoms). RESULTS: Across the full range of sonication energies that can be delivered with current devices (up to 36 kJ), average sonication HE was diminished in patients with lower SDR. In individual subjects, there was a progressive loss in HE as sonication energy was titrated up throughout the course of treatment, with a more rapid decline in patients with higher SDR. This energy-dependent loss in HE was not related to procedural factors, namely, the number of previous sonications, or the cumulative energy deposited during previous sonications. In contrast to SDR, neither skull area nor thickness was an independent predictor of average HE or the rate of its decline with increasing energies. In 11% of patients, all of whom with SDR < 0.45, sonication HE fell below the threshold to reach 54°C even with delivery of maximum energy. In contrast, temperatures ≥ 50°C could be obtained in all but one patient. CONCLUSIONS: SDR is predictive of sonication HE, and determines patient-specific limits on the magnitude of temperature elevation that can be achieved with current devices. These data inform strategies for predictable lesioning in MRgFUS thalamotomy.

The Distribution of Skull Score and Skull Density Ratio in Tremor Patients for MR-Guided Focused Ultrasound Thalamotomy.

OBJECTIVE: Magnetic resonance-guided focused ultrasound (MRgFUS) is a minimum-invasive surgical approach to non-incisionally cause the thermos-coagulation inside the human brain. The skull score (SS) has already been approved as one of the most dominant factors related to a successful MRgFUS treatment. In this study, we first reveal the SS distribution of the tremor patients, and correlate the SS with the image feature from customized skull density ratio (cSDR). This correlation might give a direction to future clinical studies for improving the SS. METHODS: Two hundred and forty-six patients received a computed tomography (CT) scan of the brain, and a bone-enhanced filter was applied and reconstructed to a high spatial resolution CT images. The SS of all patients would be estimated by the MRgFUS system after importing the reconstructed CT images into the MRgFUS system. The histogram and the cumulative distribution of the SS from all the patients were calculated to show the percentage of the patients whose SS lower than 0.3 and 0.4. The same CT images of all patients were utilized to calculated the cSDR by first segmented the trabecular bone and the cortical bone from the CT images and divided the average trabecular bone intensity (aTBI) by the average cortical bone intensity (aCBI). The Pearson's correlations between the SS and the cSDR, aTBI, and the aCBI were calculated, respectively. RESULTS: There were 19.19 and 50% of the patient who had the SS lower than the empirical threshold 0.3 and 0.4, respectively. The Pearson's correlation between the SS and the cSDR, aCBI, and the aTBI were R = 0.8145, 0.5723, and 0.8842. CONCLUSION: Half of the patients were eligible for the MRgFUS thalamotomy based on the SS, and nearly 20% of patients were empirically difficult to achieve a therapeutic temperature during MRgFUS. The SS and our cSDR are highly correlated, and the SS had a higher correlation with aTBI than with aCBI. This is the first report to explicitly reveal the SS population and indicate a potential way to increase the chance to achieve a therapeutic temperature for those who originally have low SS.

Technical and operative factors affecting magnetic resonance imaging-guided focused ultrasound thalamotomy for essential tremor: experience from 250 treatments.

OBJECTIVE: Magnetic resonance imaging-guided focused ultrasound (MRgFUS) provides real-time monitoring of patients to assess tremor control and document any adverse effects. MRgFUS of the ventral intermediate nucleus (VIM) of the thalamus has become an effective treatment option for medically intractable essential tremor (ET). The aim of this study was to analyze the correlations of clinical and technical parameters with 12-month outcomes after unilateral MRgFUS thalamotomy for ET to help guide future clinical treatments. METHODS: From October 2013 to January 2019, data on unilateral MRgFUS thalamotomy from the original pivotal study and continued-access studies from three different geographic regions were collected. Authors of the present study retrospectively reviewed those data and evaluated the efficacy of the procedure on the basis of improvement in the Clinical Rating Scale for Tremor (CRST) subscore at 1 year posttreatment. Safety was based on the rates of moderate and severe thalamotomy-related adverse events. Treatment outcomes in relation to various patient- and sonication-related parameters were analyzed in a large cohort of patients with ET. RESULTS: In total, 250 patients were included in the present analysis. Improvement was sustained throughout the 12-month follow-up period, and 184 (73.6%) of 250 patients had minimal or no disability due to tremor (CRST subscore < 10) at the 12-month follow-up. Younger age and higher focal temperature (Tmax) correlated with tremor improvement in the multivariate analysis (OR 0.948, p = 0.013; OR 1.188, p = 0.025; respectively). However, no single statistically significant factor correlated with Tmax in the multivariate analysis. The cutoff value of Tmax in predicting a CRST subscore < 10 was 55.8°C. Skull density ratio (SDR) was positively correlated with heating efficiency (ß = 0.005, p < 0.001), but no significant relationship with tremor improvement was observed. In the low-temperature group, 1-3 repetitions to the right target with 52°C ≤ Tmax ≤ 54°C was sufficient to generate sustained tremor suppression within the investigated follow-up period. The high-temperature group had a higher rate of balance disturbances than the low-temperature group (p = 0.04). CONCLUSIONS: The authors analyzed the data of 250 patients with the aim of improving practices for patient screening and determining treatment endpoints. These results may improve the safety, efficacy, and efficiency of MRgFUS thalamotomy for ET.

Correction of the skull density ratio for transcranial MRI-guided focused ultrasound thalamotomy: clinical significance of predicting therapeutic temperature.

OBJECTIVE: In transcranial magnetic resonance imaging-guided focused ultrasound (TcMRgFUS), a high skull density ratio (SDR) is advantageous to achieve a sufficiently high temperature at the target. However, it is not easy to estimate the temperature rise because the SDR shows different values depending on the reconstruction filter used. The resolution characteristic of a computed tomography (CT) image depends on a modulation transfer function (MTF) defined by the reconstruction filter. Differences in MTF induce unstable SDRs. The purpose of this study was both to standardize SDR by developing a method to correct the MTF and to enable effective patient screening prior to TcMRgFUS treatment and more accurate predictions of focal temperature. METHODS: CT images of a skull phantom and five subjects were obtained using eight different reconstruction filters. A frequency filter (FF) was calculated using the MTF of each reconstruction filter, and the validity of SDR standardization was evaluated by comparing the variation in SDR before and after FF correction. Subsequently, FF processing was similarly performed using the CT images of 18 patients who had undergone TcMRgFUS, and statistical analyses were performed comparing the relationship between the SDRs before and after correction and the maximum temperature in the target during TcMRgFUS treatment. RESULTS: The FF was calculated for each reconstruction filter based on one manufacturer's BONE filter. In the CT images of the skull phantom, the SDR before FF correction with five of the other seven reconstruction filters was significantly smaller than that with the BONE filter (p < 0.01). After FF correction, however, a significant difference was recognized under only one condition. In the CT images of the five subjects, variation of the SDR due to imaging conditions was significantly improved after the FF correction. In 18 cases treated with TcMRgFUS, there was no correlation between SDR before FF correction and maximum temperature (rs = 0.31, p > 0.05); however, a strong positive correlation was observed after FF correction (rs = 0.71, p < 0.01). CONCLUSIONS: After FF correction, the difference in SDR due to the reconstruction filter used is smaller, and the correlation with temperature is stronger. Therefore, the SDR can be standardized by applying the FF, and the maximum temperature during treatment may be predicted more accurately.

Technical Comparison of Treatment Efficiency of Magnetic Resonance-Guided Focused Ultrasound Thalamotomy and Pallidotomy in Skull Density Ratio-Matched Patient Cohorts.

OBJECTIVE: MR-guided focused ultrasound (MRgFUS) is increasingly being used to treat patients with essential tremor (ET) and Parkinson's disease (PD) with thalamotomy and pallidotomy, respectively. Pallidotomy is performed off-center within the cranium compared to thalamotomy and may present challenges to therapeutic lesioning due to this location. However, the impact of target location on treatment efficiency and ability to create therapeutic lesions has not been studied. This study aimed to compare the physical efficiency of MRgFUS thalamotomy and pallidotomy. METHODS: Treatment characteristics were compared between patients treated with thalamotomy (n = 20) or pallidotomy (n = 20), matched by skull density ratios (SDR). Aspects of treatment efficiency were compared between these groups. Demographic and comparative statistics were conducted to assess these differences. Acoustic field simulations were performed to compare and validate the simulated temperature profile for VIM and GPi ablation. RESULTS: Lower SDR values were associated with greater energy requirement for thalamotomy (R2 = 0.197, p = 0.049) and pallidotomy (R2 = 0.342, p = 0.007). The impact of low SDR on efficiency reduction was greater for pallidotomy, approaching significance (p = 0.061). A nearly two-fold increase in energy was needed to reach 50°C in pallidotomy (10.9kJ) than in thalamotomy (5.7kJ), (p = 0.002). Despite lower energy requirement, the maximum average temperature reached was higher in thalamotomy (56.7°C) than in pallidotomy (55.0°C), (p = 0.017). Mean incident angle of acoustic beams was lesser in thalamotomy (12.7°) than in pallidotomy (18.6°), (p < 0.001). For all patients, a lesser mean incident angle correlated with a higher maximum average temperature reached (R2 = 0.124, p = 0.026), and less energy needed to reach 50°C (R2=0.134, p = 0.020). Greater skull thickness was associated with a higher maximum energy for a single sonication for thalamotomy (R2 = 0.206, p = 0.045) and pallidotomy (R2 = 0.403, p = 0.003). An acoustic and temperature field simulation validated similar findings for thalamotomy and pallidotomy in a single patient. CONCLUSION: The centrally located VIM offers a more efficient location for therapeutic lesioning compared to GPi pallidotomy in SDR matched cohort of patients. The impact on therapeutic lesioning with lower SDR may be greater for pallidotomy patients. As newer off-center targets are investigated, these findings can inform patient selection and treatment requirements for lesion production.

Technical and radiographic considerations for magnetic resonance imaging-guided focused ultrasound capsulotomy.

OBJECTIVE: Magnetic resonance imaging-guided focused ultrasound (MRgFUS) is an emerging treatment modality that enables incisionless ablative neurosurgical procedures. Bilateral MRgFUS capsulotomy has recently been demonstrated to be safe and effective in treating obsessive-compulsive disorder (OCD) and major depressive disorder (MDD). Preliminary evidence has suggested that bilateral MRgFUS capsulotomy can present increased difficulties in reaching lesional temperatures as compared to unilateral thalamotomy. The authors of this article aimed to study the parameters associated with successful MRgFUS capsulotomy lesioning and to present longitudinal radiographic findings following MRgFUS capsulotomy. METHODS: Using data from 22 attempted MRgFUS capsulotomy treatments, the authors investigated the relationship between various sonication parameters and the maximal temperature achieved at the intracranial target. Lesion volume and morphology were analyzed longitudinally using structural and diffusion tensor imaging. A retreatment procedure was attempted in one patient, and their postoperative imaging is presented. RESULTS: Skull density ratio (SDR), skull thickness, and angle of incidence were significantly correlated with the maximal temperature achieved. MRgFUS capsulotomy lesions appeared similar to those following MRgFUS thalamotomy, with three concentric zones observed on MRI. Lesion volumes regressed substantially over time following MRgFUS. Fractional anisotropy analysis revealed a disruption in white matter integrity, followed by a gradual return to near-baseline levels concurrent with lesion regression. In the patient who underwent retreatment, successful bilateral lesioning was achieved, and there were no adverse clinical or radiographic events. CONCLUSIONS: With the current iteration of MRgFUS technology, skull-related parameters such as SDR, skull thickness, and angle of incidence should be considered when selecting patients suitable for MRgFUS capsulotomy. Lesions appear to follow morphological patterns similar to what is seen following MRgFUS thalamotomy. Retreatment appears to be safe, although additional cases will be necessary to further evaluate the associated safety profile.

What factors impact the clinical outcome of magnetic resonance imaging-guided focused ultrasound thalamotomy for essential tremor?

OBJECTIVE: Magnetic resonance imaging-guided focused ultrasound (MRgFUS) is a novel and useful treatment for essential tremor (ET); however, the factors impacting treatment outcome are unknown. The authors conducted this study to determine the factors affecting the outcome of MRgFUS. METHODS: From May 2016 through August 2017, 15 patients with ET were admitted to Ohnishi Neurological Center and treated with MRgFUS. To determine the factors impacting treatment outcome, the authors retrospectively studied correlations between the Clinical Rating Scale for Tremor (CRST) improvement rate and age, disease duration, baseline CRST score, skull density ratio (SDR), skull volume, maximum delivered energy, or maximum temperature. RESULTS: The mean CRST score was 18.5 ± 5.8 at baseline and 4.6 ± 5.7 at 1 year. The rate of improvement in the CRST score was 80% ± 22%. Younger age and lower baseline CRST score were correlated with a higher CRST improvement rate (p = 0.025 and 0.007, respectively). To obtain a CRST improvement rate ≥ 50%, a maximum temperature ≥ 55°C was necessary. There was no correlation between SDR and CRST improvement rate (p = 0.658). A lower SDR and higher skull volume required significantly higher maximum delivered energy (p = 0.014 and 0.016, respectively). A higher maximum temperature was associated with a significantly larger lesion volume (p = 0.026). CONCLUSIONS: Younger age and lower baseline CRST score were favorable outcome factors. It is important to assess predictive factors when applying MRgFUS.

Skull Factors Affecting Outcomes of Magnetic Resonance-Guided Focused Ultrasound for Patients with Essential Tremor.

PURPOSE: Magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy has become a standard treatment for medically intractable essential tremor (ET). Skull density ratio (SDR) and skull volume in patients with ET are currently considered useful indicators of the successful application of MRgFUS. We compared the clinical outcomes of MRgFUS thalamotomy with SDR above 0.4 and 0.45. We also described patterns of SDR and skull volume in Korean patients with ET who were eligible to be screened for MRgFUS. MATERIALS AND METHODS: In screening 318 ET patients, we evaluated patterns of skull density and skull volume according to age and sex. Fifty patients with ET were treated with MRgFUS. We investigated the effects of SDR and skull volume on treatment parameters and the outcomes of ET. RESULTS: The mean SDR of the 318 ET patients was 0.45±0.11, and that for skull volume was 315.74±40.95 cm³. The male patients had a higher SDR than female patients (p=0.047). Skull volume significantly decreased with aging. SDR and skull volume exhibited a linear negative relationship. Among therapeutic parameters, maximal temperature was positively related to SDR, while sonication number was not related to either SDR or skull volume. Tremor outcome was also not related to SDR or skull volume. CONCLUSION: SDR varied widely from 0.11 to 0.73, and men had a higher SDR. Therapeutic parameters and clinical outcomes were not affected by SDR or skull volume.

Magnetic resonance-guided focused ultrasound thalamotomy for essential tremor: a 5-year single-center experience.

OBJECTIVE: The authors report their experience in treating patients suffering from medication-resistant essential tremor (ET) with MR-guided focused ultrasound (MRgFUS) thalamotomy over a 5-year period. METHODS: Forty-four ET patients treated with unilateral MRgFUS ventral intermediate nucleus (VIM) thalamotomy were assessed using the Clinical Rating Scale for Tremor (CRST) score and the Quality of Life in Essential Tremor Questionnaire (QUEST) over a 5-year span. RESULTS: Tremor was significantly improved immediately following MRgFUS in all patients and ceased completely in 24 patients. CRST scores in the treated hand at baseline (median 19; range 7-32, 44 patients) improved by a median of 16 at 1 month (44 patients; p < 0.0001), 17 at 6 months (31 patients; p < 0.0001), 15 at 1 year (24 patients; p < 0.0001), 18 at 2 years (15 patients; p < 0.0001), 19 at 3 years, (10 patients; p < 0.0001), 21 at 4 years (6 patients; p < 0.01), and 23 at 5 years (2 patients, significance not tested). Return of tremor that impacted activities of daily living was reported in 5 patients (11%). QUEST scores showed significant improvement, with median change of 35 points (p < 0.0001; 44 patients) at 1 month, 33 (p < 0.0001; 31 patients) at 6 months, 27 (p < 0.0001; 24 patients) at 1 year, 26 (p < 0.001; 15 patients) at 2 years, 25 (p < 0.001; 10 patients) at 3 years, 33 (p < 0.001; 6 patients) at 4 years, and 28 (significance not tested, 2 patients) at 5 years. Adverse events after the procedure were reversible in all but 5 patients (11%). CONCLUSIONS: MRgFUS thalamotomy for ET is an effective and safe procedure that provides long-term tremor relief and improvement in quality of life even in patients with medication-resistant disabling tremor. Additional studies with a larger group of patients is needed to substantiate these favorable results.