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Hyun Ho Jung, Won Seok Chang, Itay Rachmilevitch, Tal Tlusty, Eyal Zadicario, and Jin Woo Chang

OBJECT

The authors report different MRI patterns in patients with essential tremor (ET) or obsessive-compulsive disorder (OCD) after transcranial MR-guided focused ultrasound (MRgFUS) and discuss possible causes of occasional MRgFUS failure.

METHODS

Between March 2012 and August 2013, MRgFUS was used to perform unilateral thalamotomy in 11 ET patients and bilateral anterior limb capsulotomy in 6 OCD patients; in all patients symptoms were refractory to drug therapy. Sequential MR images were obtained in patients across a 6-month follow-up period.

RESULTS

For OCD patients, lesion size slowly increased and peaked 1 week after treatment, after which lesion size gradually decreased. For ET patients, lesions were visible immediately after treatment and markedly reduced in size as time passed. In 3 ET patients and 1 OCD patient, there was no or little temperature rise (i.e., < 52°C) during MRgFUS. Successful and failed patient groups showed differences in their ratio of cortical-to-bone marrow thickness (i.e., skull density).

CONCLUSIONS

The authors 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.

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Won Seok Chang, Hyun Ho Jung, Eyal Zadicario, Itay Rachmilevitch, Tal Tlusty, Shuki Vitek, and Jin Woo Chang

OBJECT

Magnetic resonance-guided focused ultrasound surgery (MRgFUS) was recently introduced as treatment for movement disorders such as essential tremor and advanced Parkinson’s disease (PD). Although deep brain target lesions are successfully generated in most patients, the target area temperature fails to increase in some cases. The skull is one of the greatest barriers to ultrasonic energy transmission. The authors analyzed the skull-related factors that may have prevented an increase in target area temperatures in patients who underwent MRgFUS.

METHODS

The authors retrospectively reviewed data from clinical trials that involved MRgFUS for essential tremor, idiopathic PD, and obsessive-compulsive disorder. Data from 25 patients were included. The relationships between the maximal temperature during treatment and other factors, including sex, age, skull area of the sonication field, number of elements used, skull volume of the sonication field, and skull density ratio (SDR), were determined.

RESULTS

Among the various factors, skull volume and SDR exhibited relationships with the maximum temperature. Skull volume was negatively correlated with maximal temperature (p = 0.023, r2 = 0.206, y = 64.156 − 0.028x, whereas SDR was positively correlated with maximal temperature (p = 0.009, r2 = 0.263, y = 49.643 + 11.832x). The other factors correlate with the maximal temperature, although some factors showed a tendency to correlate.

CONCLUSIONS

Some skull-related factors correlated with the maximal target area temperature. Although the number of patients in the present study was relatively small, the results offer information that could guide the selection of MRgFUS candidates.

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So Hee Park, Myung Ji Kim, Hyun Ho Jung, Won Seok Chang, Hyun Seok Choi, Itay Rachmilevitch, Eyal Zadicario, and Jin Woo Chang

OBJECTIVE

Glioblastoma (GBM) remains fatal due to the blood-brain barrier (BBB), which interferes with the delivery of chemotherapeutic agents. The purpose of this study was to evaluate the safety and feasibility of repeated disruption of the BBB (BBBD) with MR-guided focused ultrasound (MRgFUS) in patients with GBM during standard adjuvant temozolomide (TMZ) chemotherapy.

METHODS

This study was a prospective, single-center, single-arm study. BBBD with MRgFUS was performed adjacent to the tumor resection margin on the 1st or 2nd day of the adjuvant TMZ chemotherapy at the same targets for 6 cycles. T2*-weighted/gradient echo (GRE) MRI was performed immediately after every sonication trial, and comprehensive MRI was performed at the completion of all sonication sessions. Radiological, laboratory, and clinical evaluations were performed 2 days before each planned BBBD.

RESULTS

From September 2018, 6 patients underwent 145 BBBD trials at various locations in the brain. The authors observed gadolinium-enhancing spots at the site of BBBD on T1-weighted MRI in 131 trials (90.3%) and 93 trials (64.1%) showed similar spots on T2*-weighted/GRE MRI. When the 2 sequences were combined, BBBD was observed in 134 targets (92.4%). The spots disappeared on follow-up MRI. There were no imaging changes related to BBBD and no clinical adverse effects during the 6 cycles.

CONCLUSIONS

This study is the first in which repetitive MRgFUS was performed at the same targets with a standard chemotherapy protocol for malignant brain tumor. BBBD with MRgFUS was performed accurately, repeatedly, and safely. Although a longer follow-up period is needed, this study allows for the possibility of other therapeutic agents that previously could not be used due to the BBB.

Clinical trial registration no.: NCT03712293 (clinicaltrials.gov)

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Myung Ji Kim, So Hee Park, Kyung Won Chang, Yuhee Kim, Jing Gao, Maya Kovalevsky, Itay Rachmilevitch, Eyal Zadicario, Won Seok Chang, Hyun Ho Jung, and Jin Woo Chang

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 (β = 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.