Predicting final lesion characteristics during MR-guided focused ultrasound pallidotomy for treatment of Parkinson's disease.

OBJECTIVE: Magnetic resonance-guided focused ultrasound (MRgFUS) ablation of the globus pallidus interna (GPi) is being investigated for the treatment of advanced Parkinson's disease symptoms. However, GPi lesioning presents unique challenges due to the off-midline location of the target. Furthermore, it remains uncertain whether intraprocedural MR thermometry data can predict final lesion characteristics. METHODS: The authors first performed temperature simulations of GPi pallidotomy and compared the results with those of actual cases and the results of ventral intermediate nucleus (VIM) thalamotomy performed for essential tremor treatment. Next, thermometry data from 13 MRgFUS pallidotomy procedures performed at their institution were analyzed using 46°C, 48°C, 50°C, and 52°C temperature thresholds. The resulting thermal models were compared with resulting GPi lesions noted on postprocedure days 1 and 30. Finally, the treatment efficiency (energy per temperature rise) of pallidotomy was evaluated. RESULTS: The authors' modeled acoustic intensity maps correctly demonstrate the elongated, ellipsoid lesions noted during GPi pallidotomy. In treated patients, the 48°C temperature threshold maps most accurately predicted postprocedure day 1 lesion size, while no correlation was found for day 30 lesions. The average energy/temperature rise of pallidotomy was higher (612 J/°C) than what had been noted for VIM thalamotomy and varied with the patients' skull density ratios (SDRs). CONCLUSIONS: The authors' acoustic simulations accurately depicted the characteristics of thermal lesions encountered following MRgFUS pallidotomy. MR thermometry data can predict postprocedure day 1 GPi lesion characteristics using a 48°C threshold model. Finally, the lower treatment efficiency of pallidotomy may make GPi lesioning challenging in patients with a low SDR.

Three-year follow-up of prospective trial of focused ultrasound thalamotomy for essential tremor.

OBJECTIVE: To test the hypothesis that transcranial magnetic resonance-guided focused ultrasound (tcMRgFUS) thalamotomy is effective, durable, and safe for patients with medication-refractory essential tremor (ET), we assessed clinical outcomes at 3-year follow-up of a controlled multicenter prospective trial. METHODS: Outcomes were based on the Clinical Rating Scale for Tremor, including hand combined tremor-motor (scale of 0-32), functional disability (scale of 0-32), and postural tremor (scale of 0-4) scores, and total scores from the Quality of Life in Essential Tremor Questionnaire (scale of 0-100). Scores at 36 months were compared with baseline and at 6 months after treatment to assess for efficacy and durability. Adverse events were also reported. RESULTS: Measured scores remained improved from baseline to 36 months (all p < 0.0001). Range of improvement from baseline was 38%-50% in hand tremor, 43%-56% in disability, 50%-75% in postural tremor, and 27%-42% in quality of life. When compared to scores at 6 months, median scores increased for hand tremor (95% confidence interval [CI] 0-2, p = 0.0098) and disability (95% CI 1-4, p = 0.0001). During the third follow-up year, all previously noted adverse events remained mild or moderate, none worsened, 2 resolved, and no new adverse events occurred. CONCLUSIONS: Results at 3 years after unilateral tcMRgFUS thalamotomy for ET show continued benefit, and no progressive or delayed complications. Patients may experience mild degradation in some treatment metrics by 3 years, though improvement from baseline remains significant. CLINICALTRIALSGOV IDENTIFIER: NCT01827904. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that for patients with severe ET, unilateral tcMRgFUS thalamotomy provides durable benefit after 3 years.

Targeting of the dentato-rubro-thalamic tract for MR-guided focused ultrasound treatment of essential tremor.

BACKGROUND: Magnetic resonance-guided focused ultrasound ablation of the thalamic ventral intermediate nucleus is a safe and effective treatment for medically refractory essential tremor. However, indirect targeting of the ventral intermediate nucleus using stereotactic coordinates from normal neuroanatomy can be inefficient. We therefore evaluated the feasibility of supplementing this method with direct targeting of the dentato-rubro-thalamic tract. METHODS: We retrospectively identified four patients undergoing magnetic resonance-guided focused ultrasound ablation for essential tremor in which preoperative diffusion tractography imaging of the dentato-rubro-thalamic tract was fused with T2 weighted-imaging and utilized for intra-procedural targeting. The size and location of the dentato-rubro-thalamic tract and 24-hour lesion, as well as the center of the stereotactic coordinates, was evaluated. Finally, the amount of overlap between the dentato-rubro-thalamic tract and the lesion was calculated. RESULTS: The 24-hour lesion size was homogeneous in the cohort (mean 31.3 mm2, range 30-32 mm2), while there was substantial variation in the dentato-rubro-thalamic tract area (mean 14.3 mm2, range 3-24 mm2). The center of the stereotactic coordinates and dentato-rubro-thalamic tract diverged by more than 1 mm in mediolateral and anterposterior directions in all patients, while the dentato-rubro-thalamic tract and lesion centers were in close proximity (mean mediolateral separation 1 mm, range 0.1-2.2 mm; mean anteroposterior separation 0.75 mm, range 0.4-1.2 mm). There was greater than 50% coverage of the dentato-rubro-thalamic tract by the lesion in all patients (mean 82.9%, range 66.7-100%). All patients experienced durable tremor relief. CONCLUSION: Direct targeting of the dentato-rubro-thalamic tract using diffusion tractography imaging fused to T2 weighted-imaging may be a useful strategy for focused ultrasound treatment of essential tremor. Further investigation of the technique is warranted.

Influence of Intracerebral Hemorrhage Location on Outcomes in Patients With Severe Intraventricular Hemorrhage.

Background and Purpose- We investigated the prognostic significance of spontaneous intracerebral hemorrhage location in presence of severe intraventricular hemorrhage. Methods- We analyzed diagnostic computed tomography scans from 467/500 (excluding primary intraventricular hemorrhage) subjects from the CLEAR (Clot Lysis: Evaluating Accelerated Resolution of Intraventricular Hemorrhage) III trial. We measured intracerebral hemorrhage engagement with specific anatomic regions, and estimated association of each region with blinded assessment of dichotomized poor stroke outcomes: mortality, modified Rankin Scale score of 4 to 6, National Institutes of Health Stroke Scale score of >4, stroke impact scale score of <60, Barthel Index <86, and EuroQol visual analogue scale score of <50 and <70 at days 30 and 180, respectively, using logistic regression models. Results- Frequency of anatomic region involvement consisted of thalamus (332 lesions, 71.1% of subjects), caudate (219, 46.9%), posterior limb internal capsule (188, 40.3%), globus pallidus/putamen (127, 27.2%), anterior limb internal capsule (108, 23.1%), and lobar (29, 6.2%). Thalamic location was independently associated with mortality (days 30 and 180) and with poor outcomes on most stroke scales at day 180 on adjusted analysis. Posterior limb internal capsule and globus pallidus/putamen involvement was associated with increased odds of worse disability at days 30 and 180. Anterior limb internal capsule and caudate locations were associated with decreased mortality on days 30 and 180. Anterior limb internal capsule lesions were associated with decreased long-term morbidity. Conclusions- Acute intracerebral hemorrhage lesion topography provides important insights into anatomic correlates of mortality and functional outcomes even in severe intraventricular hemorrhage causing obstructive hydrocephalus. Models accounting for intracerebral hemorrhage location in addition to volumes may improve outcome prediction and permit stratification of benefit from aggressive acute interventions. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifier: NCT00784134.

A Randomized Trial of Focused Ultrasound Thalamotomy for Essential Tremor.

BACKGROUND: Uncontrolled pilot studies have suggested the efficacy of focused ultrasound thalamotomy with magnetic resonance imaging (MRI) guidance for the treatment of essential tremor. METHODS: We enrolled patients with moderate-to-severe essential tremor that had not responded to at least two trials of medical therapy and randomly assigned them in a 3:1 ratio to undergo unilateral focused ultrasound thalamotomy or a sham procedure. The Clinical Rating Scale for Tremor and the Quality of Life in Essential Tremor Questionnaire were administered at baseline and at 1, 3, 6, and 12 months. Tremor assessments were videotaped and rated by an independent group of neurologists who were unaware of the treatment assignments. The primary outcome was the between-group difference in the change from baseline to 3 months in hand tremor, rated on a 32-point scale (with higher scores indicating more severe tremor). After 3 months, patients in the sham-procedure group could cross over to active treatment (the open-label extension cohort). RESULTS: Seventy-six patients were included in the analysis. Hand-tremor scores improved more after focused ultrasound thalamotomy (from 18.1 points at baseline to 9.6 at 3 months) than after the sham procedure (from 16.0 to 15.8 points); the between-group difference in the mean change was 8.3 points (95% confidence interval [CI], 5.9 to 10.7; P<0.001). The improvement in the thalamotomy group was maintained at 12 months (change from baseline, 7.2 points; 95% CI, 6.1 to 8.3). Secondary outcome measures assessing disability and quality of life also improved with active treatment (the blinded thalamotomy cohort)as compared with the sham procedure (P<0.001 for both comparisons). Adverse events in the thalamotomy group included gait disturbance in 36% of patients and paresthesias or numbness in 38%; these adverse events persisted at 12 months in 9% and 14% of patients, respectively. CONCLUSIONS: MRI-guided focused ultrasound thalamotomy reduced hand tremor in patients with essential tremor. Side effects included sensory and gait disturbances. (Funded by InSightec and others; ClinicalTrials.gov number, NCT01827904.).

State of the art head and neck imaging for the endovascular specialist.

Recent technologic advances including multidetector CT, dynamic CT angiography, high-field MR imaging, four-dimensional MR angiography, and physiologic studies, such as perfusion imaging, have revolutionized the imaging work-up of head, neck, and skull base lesions. These techniques not only provide accurate diagnostic information, but also help plan endovascular therapy. The future holds great promise for interventional neuroradiologists because excellent imaging tools are becoming available that are capable of providing morphologic, hemodynamic, and physiologic information. Furthermore, availability of faster, real-time guidance systems and hybrid systems improves the ability to perform procedures not only in a rapid and safe manner but also with great precision.