MRI-guided Focused Ultrasound Research Articles

Treatment of vocal tremor with bilateral magnetic resonance imaging-guided focused ultrasound of the ventral intermediate thalamic nucleus: illustrative case.

Essential vocal tremor is a difficult disease entity to treat with a poor response to existing medical management and limited options for surgical management of the disease. Magnetic resonance imaging-guided focused ultrasound (MRgFUS) is an emerging treatment modality with encouraging results for limb tremor in patients with essential tremor, but data are limited for the treatment of vocal tremor. This is the case of a 69-year-old male with a history of essential vocal tremor severely limiting his ability to perform his occupation as an opera singer. He underwent staged bilateral ventral intermediate nucleus of the thalamus thalamotomy with MRgFUS for the treatment of his bilateral upper extremity tremor with near complete resolution of his vocal tremor after a second procedure. Bilateral MRgFUS may be a safe and efficacious option for the treatment of essential vocal tremor. Further research into optimal patient selection, precise target location, and treatment parameters is needed.

Tumor phantom model for MRI-guided focused ultrasound ablation studies.

The persistent development of focused ultrasound (FUS) thermal therapy in the context of oncology creates the need for tissue-mimicking tumor phantom models for early-stage experimentation and evaluation of relevant systems and protocols. This study presents the development and evaluation of a tumor-bearing tissue phantom model for testing magnetic resonance imaging (MRI)-guided FUS (MRgFUS) ablation protocols and equipment based on MR thermometry. Normal tissue was mimicked by a pure agar gel, while the tumor simulator was differentiated from the surrounding material by including silicon dioxide. The phantom was characterized in terms of acoustic, thermal, and MRI properties. US, MRI, and computed tomography (CT) images of the phantom were acquired to assess the contrast between the two compartments. The phantom's response to thermal heating was investigated by performing high power sonications with a 2.4 MHz single element spherically focused ultrasonic transducer in a 3T MRI scanner. The estimated phantom properties fall within the range of literature-reported values of soft tissues. The inclusion of silicon dioxide in the tumor material offered excellent tumor visualization in US, MRI, and CT. MR thermometry revealed temperature elevations in the phantom to ablation levels and clear evidence of larger heat accumulation within the tumor owing to the inclusion of silicon dioxide. Overall, the study findings suggest that the proposed tumor phantom model constitutes a simple and inexpensive tool for preclinical MRgFUS ablation studies, and potentially other image-guided thermal ablation applications upon minimal modifications.

Molecular Identity Changes of Tumor-Associated Macrophages and Microglia After Magnetic Resonance Imaging-Guided Focused Ultrasound-Induced Blood-Brain Barrier Opening in a Mouse Glioblastoma Model.

An orthotopically allografted mouse GL26 glioma model (Ccr2RFP/wt-Cx3cr1GFP/wt) was used to evaluate the effect of transient, focal opening of the blood-brain barrier (BBB) on the composition of tumor-associated macrophages and microglia (TAMs). BBB opening was induced by magnetic resonance imaging (MRI)-guided focused ultrasound (MRgFUS) combined with microbubbles. CX3CR1-GFP cells and CCR2-RFP cells in brain tumors were quantified in microscopic images. Tumors in animals treated with a single session of MRgFUS did not exhibit significant changes in cell numbers when compared with tumors in animals not receiving FUS. However, tumors that received two or three sessions of MRgFUS had significantly increased amounts of both CX3CR1-GFP and CCR2-RFP cells. The effect of MRgFUS on immune cell composition was also characterized and quantified using flow cytometry. Glioma implantation resulted in increased amounts of lymphocytes, monocytes and neutrophils in the brain parenchyma. Tumors administered MRgFUS exhibited increased numbers of monocytes and monocyte-derived TAMs. In addition, MRgFUS-treated tumors exhibited more CD80+ cells in monocytes and microglia. In summary, transient, focal opening of the BBB using MRgFUS combined with microbubbles can activate the homing and differentiation of monocytes and induce a shift toward a more pro-inflammatory status of the immune environment in glioblastoma.

501 Patient-Specific Targeting Method for Improved Quality-of-Life Outcomes from MRgFUS Treatment of Essential Tremor

INTRODUCTION: MRI-guided-focused-ultrasound (MRgFUS) ablation of the ventral intermediate nucleus (VIM) is an FDA-approved treatment for essential tremor (ET). However, the VIM cannot be directly visualized on standard imaging, and the ideal ablation zone within the putative VIM varies inter-individually. Suboptimal lesion location can lead to side effects that impair quality of life (QoL). Patient-specific methods to locate the “go-zone” for MRgFUS ablation for ET that can predict QoL outcome could provide significant benefit over current methods. METHODS: We retrospectively studied 26 ET patients treated with MRgFUS at Stanford. Probabilistic tracking from the thalamus to M1 using each subject’s standard, low-resolution preoperative diffusion MRI generated patient-specific cerebello-thalamic-cortical tracts. Within the thalamus, the personalized hotspot with high probability of being connected to M1 defined the “go-zone.” The normative DISTAL-atlas VIM, which some centers use to target deep brain stimulation, provided a comparison. The lesion was segmented in postoperative MRIs and transformed to the preoperative-MRI space. Similarity/overlap between the “go-zone” and lesion was quantified using the Sorensen-Dice coefficient. Postoperative QoL ("better," "same," or "worse") was determined from each subject’s last-available follow-up. RESULTS: Probabilistic thalamus-to-M1 tracking robustly identified cerebello-thalamo-cortical tracts using standard, clinical diffusion MRIs. Lesion similarity to the patient-specific tractographic "go-zone" was associated with better QoL outcomes. Dice coefficients of the "worse" group were significantly lower than of the combined “same”/”better” group (p = 0.014). This was not seen with the DISTAL-atlas VIM. CONCLUSIONS: We proposed a clinically-feasible probabilistic-tractography-based targeting method for MRgFUS treatment of ET. Lesion similarity to the personalized “go-zone” is associated with better QoL outcome, unlike similarity to the normative DISTAL-atlas VIM. This illustrates the value of our patient-specific targeting approach.

Characteristics of Pain During MRI-Guided Focused Ultrasound Thalamotomy.

Magnetic resonance imaging-guided focused ultrasound (MRgFUS) has become popular as an incisionless mode of neurosurgical treatment. However, head pain during sonication is common and its pathophysiology remains poorly understood. To explore the characteristics of head pain occurring during MRgFUS thalamotomy. Our study comprised 59 patients who answered questions about the pain they experienced during unilateral MRgFUS thalamotomy. The location and features of pain were investigated using a questionnaire including the numerical rating scale (NRS) to estimate maximum pain intensity and the Japanese version of the Short Form of McGill Pain Questionnaire 2 to evaluate the quantitative and qualitative dimensions of pain. Several clinical factors were investigated for possible correlation with pain intensity. Forty-eight patients (81%) reported sonication-related head pain, and the degree of pain was severe (NRS score ≥ 7) in 39 patients (66%). The distribution of sonication-related pain was "localized" in 29 (49%) and "diffuse" in 16 (27%); the most frequent location was the "occipital" region. The pain features most frequently reported were those in the "affective" subscale of the Short Form of McGill Pain Questionnaire 2. Patients with diffuse pain had a higher NRS score and lower skull density ratio than did patients with localized pain. The NRS score negatively correlated with tremor improvement at 6 months post-treatment. Most patients in our cohort experienced pain during MRgFUS. The distribution and intensity of pain varied according to the skull density ratio, indicating that the pain might have had different origins. Our results may contribute to the improvement of pain management during MRgFUS.

Evaluation of a Developed MRI-Guided Focused Ultrasound System in 7 T Small Animal MRI and Proof-of-Concept in a Prostate Cancer Xenograft Model to Improve Radiation Therapy.

Focused ultrasound (FUS) can be used to physiologically change or destroy tissue in a non-invasive way. A few commercial systems have clinical approval for the thermal ablation of solid tumors for the treatment of neurological diseases and palliative pain management of bone metastases. However, the thermal effects of FUS are known to lead to various biological effects, such as inhibition of repair of DNA damage, reduction in tumor hypoxia, and induction of apoptosis. Here, we studied radiosensitization as a combination therapy of FUS and RT in a xenograft mouse model using newly developed MRI-compatible FUS equipment. Xenograft tumor-bearing mice were produced by subcutaneous injection of the human prostate cancer cell line PC-3. Animals were treated with FUS in 7 T MRI at 4.8 W/cm2 to reach ~45 °C and held for 30 min. The temperature was controlled via fiber optics and proton resonance frequency shift (PRF) MR thermometry in parallel. In the combination group, animals were treated with FUS followed by X-ray at a single dose of 10 Gy. The effects of FUS and RT were assessed via hematoxylin-eosin (H&E) staining. Tumor proliferation was detected by the immunohistochemistry of Ki67 and apoptosis was measured by a TUNEL assay. At 40 days follow-up, the impact of RT on cancer cells was significantly improved by FUS as demonstrated by a reduction in cell nucleoli from 189 to 237 compared to RT alone. Inhibition of tumor growth by 4.6 times was observed in vivo in the FUS + RT group (85.3%) in contrast to the tumor volume of 393% in the untreated control. Our results demonstrated the feasibility of combined MRI-guided FUS and RT for the treatment of prostate cancer in a xenograft mouse model and may provide a chance for less invasive cancer therapy through radiosensitization.

Beyond the AJR: MRI-Guided Focused Ultrasound Focal Therapy for Intermediate-Risk Prostate Cancer.

Beyond the AJR: MRI-Guided Focused Ultrasound Focal Therapy for Intermediate-Risk Prostate CancerSangeet Ghai, MD1 and Nathan Perlis, MD2Audio Available | Share

Formulation of a kit under Good Manufacturing Practices (GMP) for preparing [111In]In-BnDTPA-trastuzumab-NLS injection: a theranostic agent for imaging and Meitner-Auger Electron (MAE) radioimmunotherapy of HER2-positive breast cancer

Background111In[In]-BnDTPA-trastuzumab-NLS is a radiopharmaceutical with theranostic applications for imaging and Meitner-Auger electron (MAE) radioimmunotherapy (RIT) of HER2-positive breast cancer (BC). Nuclear localization sequence (NLS) peptides route the radiopharmaceutical to the nucleus of HER2-positive BC cells following receptor-mediated internalization for RIT with subcellular range MAEs. The γ-photons emitted by 111In permit tumour imaging by SPECT. Our aim was to formulate a kit under Good Manufacturing Practices conditions to prepare 111In[In]-BnDTPA-trastuzumab-NLS injection for a first-in-human clinical trial.ResultsTrastuzumab was derivatized with p-SCN-BnDTPA to introduce Bn-DTPA for complexing 111In, then modified with maleimide groups for conjugation to the thiol on cysteine in NLS peptides [CGYGPKKKRKVGG]. BnDTPA-trastuzumab-NLS (5 mg in 1.0 mL of 0.05 M ammonium acetate buffer, pH 5.5) was dispensed into unit dose sterile glass vials to produce kits for labeling with 100–165 MBq of 111In[In]Cl3. The kits met specifications for protein concentration (4.5–5.5 mg/mL), volume (0.95–1.05 mL), pH (5.5–6.0), appearance (clear, pale-yellow, particulate-free), BnDTPA substitution level (2.0–7.0 BnDTPA/trastuzumab), purity and homogeneity (SDS-PAGE and SE-HPLC), 111In labeling efficiency (> 90%), binding to HER2-positive SK-BR-3 human breast cancer cells (Ka = 1–8 × 108 L/mmol; Bmax = 0.5–2 × 106 sites/cell), NLS peptide conjugation (upward band shift on SDS-PAGE), sterility (USP Sterility Test) and endotoxins (USP Bacterial Endotoxins Test). 111In-BnDTPA-trastuzumab-NLS injection met specifications for pH (5.5–6.5), radiochemical purity (≥ 90%), radionuclide purity (≥ 99%), appearance (clear, colourless, particle-free) and sterility (retrospective USP Sterility Test). Kits were stable stored at 2–8 °C for up to 661 days (d) meeting all key specifications. Protein concentration remained within or just slightly greater than the specification for up to 139 d. 111In[In]-BnDTPA-trastuzumab-NLS injection was stable for up to 24 h. An expiry of 180 d was assigned for the kits and 8 h for the final radiopharmaceutical.ConclusionA kit was formulated under GMP conditions for preparing 111In[In]-BnDTPA-trastuzumab-NLS injection. This radiopharmaceutical was safely administered to 4 patients with HER2-positive BC to trace the uptake of trastuzumab into brain metastases before and after MRI-guided focused ultrasound (MRIg-FUS) by SPECT imaging.

Complete resolution of chronic cluster headache following central lateral thalamotomy using incisionless MRI-guided focused ultrasound with 6 years of follow-up: illustrative case.

The authors reported the case of a 66-year-old male patient with a 14-year history of right-sided severe episodic and therapy-resistant cluster headache (CH) who underwent bilateral central lateral thalamotomy (CLT) using incisionless transcranial magnetic resonance imaging-guided focused ultrasound (MRgFUS). The patient experienced a single cluster headache attack 5 weeks after the procedure. There were no more pain attacks over the next 6 years of follow-up. This treatment success may indicate a common pathophysiology for CH and neurogenic (neuropathic) pain, which has been treated with CLT for more than 30 years. Further experience is needed to assess the reproducibility of this case.

Pretherapeutic functional connectivity of tractography-based targeting of the ventral intermediate nucleus for predicting tremor response in patients with Parkinson's disease after thalamotomy with MRI-guided focused ultrasound.

Tractography-based direct targeting of the ventral intermediate nucleus (T-VIM) is a novel method that provides patient-specific VIM coordinates. This study aimed to explore the accuracy and predictive value of using T-VIM in combination with tractography and resting-state functional connectivity techniques to perform magnetic resonance imaging-guided focused ultrasound (MRgFUS) thalamotomy as a treatment of Parkinson's disease (PD). PD patients underwent MRgFUS thalamotomy and were recruited for functional MRI scanning. A subscore of the Clinical Rating Scale for Tremor was used to evaluate tremor improvement. T-VIM and surgical VIM (S-VIM) were defined on preoperative diffusion tensor MRI and 24-hour postoperative T1-weighted imaging, respectively. The overlapping volume and center distance between S-VIM and T-VIM were measured to determine their correlations with 12-month postoperative tremor improvement. Moreover, pretherapeutic functional connectivity of T-VIM or S-VIM, based on region-of-interest connectivity and whole-brain seed-to-voxel connectivity, was measured with the resting-state functional connectivity technique to investigate their correlations with tremor improvement. All patients had excellent tremor improvement (mean [range] tremor improvement 74.82% [50.00%-94.44%]). The authors found that both overlapping volume and center distance between T-VIM and S-VIM were significantly correlated with tremor improvement (r = 0.788 and p = 0.012 for overlapping volume; r = -0.696 and p = 0.037 for center distance). Pretherapeutic functional connectivity of T-VIM with the ipsilateral sensorimotor cortex (r = 0.876 and p = 0.002), subthalamic nucleus (r = 0.700 and p = 0.036), and visual area (r = 0.911 and p = 0.001) was significantly and positively correlated with tremor improvement. T-VIM may improve the clinical application of MRgFUS thalamotomy as a treatment of PD. Pretherapeutic functional connectivity of T-VIM with the ipsilateral sensorimotor cortex, subthalamic nucleus, and visual area may predict PD tremor responses after MRgFUS thalamotomy.

Homoeopathic constitutional medicine helps to cure ovarian cyst: A case report

Introduction: In female’s Ovarian Cyst is a very common benign gynaecological tumour, especially during their reproductive years and affecting 20-50% of women this day. As a result of this disease, so many symptoms are found such as irregular and painful menstruation & also true 75% of cases are asymptomatic. There is only treatment OCs include medical therapies, surgery, and newer options such as MRI-guided focused ultrasound (MRgFUS). The post-operative complication is very common for Ovarian Cyst. We present a case report that constitutional individualized homoeopathic medicines can also recover Ovarian Cyst without any complications & side effects. Homoeopathy can be a good alternative treatment for the management of Ovarian Cyst. Case Summary: A 21-year-old, Hindu, unmarried woman from middle-class status family present at O.P.D of Kharagpur Homoeopathic Hospital. Her chief complaint was painful irregular menstruation with drowsiness. She was suffering from severe pain in the right iliac fossa & lumber region. The character of pain was stitching, cutting & gradually increasing. Pain starts 1 to 2 days prior to menstruation & ended after 3 to 4 days of menstruation.

Re: MRI-guided Focused Ultrasound Focal Therapy for Patients with Intermediate-risk Prostate Cancer: A Phase 2b, Multicentre Study

Re: MRI-guided Focused Ultrasound Focal Therapy for Patients with Intermediate-risk Prostate Cancer: A Phase 2b, Multicentre Study

Treatment-Specific Network Modulation of MRI-Guided Focused Ultrasound Thalamotomy in Essential Tremor

MRI-guided focused ultrasound (MRgFUS) thalamotomy is a novel, effective, and non-invasive treatment for essential tremor (ET). However, the network mediating MRgFUS in treating ET is not precisely known. This study aimed to identify the disease-specific network associated with the therapeutic effects of MRgFUS thalamotomy on ET and investigate its regional characteristics and genetic signatures to gain insights into the neurobiological mechanism of ET and MRgFUS thalamotomy. Twenty-four ET patients treated with MRgFUS thalamotomy underwent resting-state functional MRI at baseline and postoperative 6 months to measure the fractional amplitude of low-frequency fluctuation (fALFF). Ordinal trends canonical variates analysis (OrT/CVA) was performed on the within-subject fALFF data to identify the ET-related network. Genetic functional enrichment analysis was conducted to study the genetic signatures of this ET-related network using brain-wide gene expression data. OrT/CVA analysis revealed a significant ET-related network for which subject expression showed consistent increases after surgery. The treatment-induced increases in subject expression were significantly correlated with concurrent tremor improvement. This network was characterized by increased activity in the sensorimotor cortex and decreased activity in the posterior cingulate cortex. It was correlated with an expression map of a weighted combination genes enriched for mitochondria relevant ontology terms. This study demonstrates that the therapeutic effects of MRgFUS thalamotomy on ET are associated with modulating a distinct ET-related network which may be driven by mitochondria relevant neurobiological mechanism. Quantification of treatment-induced modulation on the ET-related network can provide an objective marker for evaluating the efficacy of MRgFUS thalamotomy.

Update in the clinical application of focused ultrasound.

To review the most recent evidence about the clinical applicability of transcranial MRI-guided focused ultrasound (MRgFUS), including clinical evidence and indications, recent technical developments for its use and future prospects. Unilateral MRgFUS thalamotomy for both essential and parkinsonian tremors is an approved and well established therapy. Recent studies have focused on its long-term safety and efficacy as well as technical advances for refining the approach. Moreover, ultrasound has expanded its application in Parkinson's disease, with clinical trials successfully targeting other brain regions like the subthalamic nucleus, the globus pallidus and the pallidothalamic tract, providing benefits for features that thalamotomy neglects. New indications, such as focal dystonia or neuropsychiatric conditions (namely obsessive-compulsive disorder and depression) have also been explored, with encouraging preliminary results. Finally, the application of ultrasound in low-intensity modality allows other approaches like focal blood-brain barrier opening and neuromodulation, which promise to be highly relevant in translational research. MRgFUS is a growing emergent technique. Its application in clinical routine is becoming widely accepted as a therapeutic option. Novel approaches and new potential applications are anticipated.

First use of MRI-guided focused ultrasound to treat patients with essential tremor in Russia

Introduction. Treatment with MRI-guided focused ultrasound (MRgFUS) is a new, non-invasive surgical technique for treating extrapyramidal movement disorders. This article presents the first use of MRgFUS in Russia for treating patients with essential tremor (ET).
 Materials and methods. Patients (n = 26; 17 men and 9 women) aged 2182 years (median age 46.0 years) and with severe and refractory ET, underwent MRgFUS thalamotomy (ExAblate 4000, Insightec). One side was treated in 22 patients (left thalamus in 18 and right thalamus in 6), both sides were treated concurrently in two patients, and both sides were treated consecutively in two patients. Tremor was assessed using the Clinical Rating Scale for Tremor (CRST). Because international clinical specialists could not visit Russia due to the COVID-19 pandemic, MRgFUS was performed via telehealth on May 5, 2020, in a world first.
 Results. A satisfactory result was achieved in 25 (96%) out of 26 patients. CRST scores improved by 64.7% on the side of the operation, by 10.2% on the control side, and by 37.5% overall. Intraoperative side effects included headache during sonication (42.3%), vertigo (15.4%), nausea (11.5%), vomiting (7.7%), numbness (3.8%), ataxia (3.8%), and pathological response to cold exposure (3.8%). The symptoms resolved immediately after surgery. Unstable gait was noted in five patients, which completely resolved two weeks after surgery. Median postoperative follow-up duration was 109 days [53; 231], with a maximum of 625 days. No relapses (if the hyperkinesia had completely disappeared) or increased tremor (if reduced after surgery) were observed.
 Conclusion. The efficacy of MRgFUS for ET was 96%, with no long-term complications. Both bilateral concurrent and bilateral consecutive MRgFUS thalamotomy is possible, but its efficacy and safety should be assessed in a randomized study. In a world first, MRgFUS was successfully implemented using telehealth.

A Modified Bowel Displacement Technique for Magnetic Resonance Imaging–Guided Focused Ultrasound Surgery in the Treatment of Uterine Fibroids and Adenomyosis

The clinical application of magnetic resonance imaging-guided focused ultrasound (MRgFUS) surgery for treatment of symptomatic uterine fibroids is often limited because of the bowel between the abdominal wall and uterus. If bowels are in the pathway of sonication path, firstly filling the bladder, then filling the rectum, and emptying the bladder subsequently can be used to avoid them in recent research. The purpose of this study was to evaluate whether the modified bowel displacement technique (rectal filling first and then bladder filling, with or without subsequent bladder emptying) was feasible to create secure acoustic window. A total of 78 patients who had undergone MRgFUS treatment for uterine fibroids and adenomyosis from January 2020 to November 2020 were included in this retrospective study. Of the 78 patients, 19 patients were treated using a modified bowel displacement technique, whereas the rest of the patients did not require intestinal displacement. High-intensity focused ultrasound was performed using GE Sightec HDXT 1.5 Tesla MR and ExAblate high-intensity focused ultrasound system. Of the 19 patients requiring bowel displacement techniques, 17 patients successfully completed MRgFUS surgery. Magnetic resonance imaging-guided focused ultrasound surgery was feasible in 4 patients after rectal filling, bladder filling, and subsequent bladder emptying. The others received ablation through the extended bladder because of bowel descending after emptying the bladder. The surgery caused no intestinal or uterine complications and no serious discomfort to the patient. The modified bowel displacement technique was effective in displacing interposed bowels during MRgFUS treatment to create safe acoustic pathway for ablating uterine fibroids and adenomyosis.

Correlation of visual area with tremor improvement after MRgFUS thalamotomy in Parkinson's disease.

MRI-guided focused ultrasound (MRgFUS) thalamotomy is a novel and minimally invasive alternative for medication-refractory tremor in Parkinson's disease (PD). However, the impact of MRgFUS thalamotomy on spontaneous neuronal activity in PD remains unclear. The purpose of the current study was to evaluate the effects of MRgFUS thalamotomy on local fluctuations in neuronal activity as measured by the fractional amplitude of low-frequency fluctuations (fALFF) in patients with PD. Participants with PD undergoing MRgFUS thalamotomy were recruited. Tremor scores were assessed before and 3 and 12 months after treatment using the Clinical Rating Scale for Tremor. MRI data were collected before and 1 day, 1 week, 1 month, 3 months, and 12 months after thalamotomy. The fALFF was calculated. A whole-brain voxel-wise paired t-test was used to identify significant changes in fALFF at 12 months after treatment compared to baseline. Then fALFF in the regions with significant differences were extracted from fALFF maps of patients for further one-way repeated-measures ANOVA to investigate its dynamic alterations. The association between fALFF changes induced by thalamotomy and tremor improvement were evaluated using the nonparametric Spearman rank test. Nine participants with PD (mean age ± SD 64.7 ± 6.1 years, 8 males) were evaluated. Voxel-based analysis showed that fALFF in the left occipital cortex (Brodmann area 17 [BA17]) significantly decreased at 12 months after thalamotomy compared to baseline (voxel p < 0.001, cluster p < 0.05 family-wise error [FWE] corrected). At baseline, fALFF in the left occipital BA17 in patients was elevated compared with that in 9 age- and gender-matched healthy subjects (p < 0.05). Longitudinal analysis displayed the dynamic changes of fALFF in this region (F (5,40) = 3.61, p = 0.009). There was a significant positive correlation between the falling trend in fALFF in the left occipital BA17 and hand tremor improvement after treatment over 3 time points (Spearman's rho = 0.44, p = 0.02). The present study investigated the impact of MRgFUS ventral intermediate nucleus thalamotomy on spontaneous neural activity in medication-refractory tremor-dominant PD. The visual area is, for the first time, reported as relevant to tremor improvement in PD after MRgFUS thalamotomy, suggesting a distant effect of MRgFUS thalamotomy and the involvement of specific visuomotor networks in tremor control in PD.

Essential Tremor-Do We Have Better Therapeutics? A Review of Recent Advances and Future Directions.

Essential tremor (ET) is a very common condition that significantly impacts quality of life. Current medical treatments are quite limited, and while surgical treatments like deep brain stimulation (DBS) can be very effective, they come with their own limitations as well as procedural risks. This article reviews updates on recent advances and future directions in the treatment of ET. A new generation of pharmacologic agents specifically designed for ET is in clinical trials. Advances in DBS technology continue to improve this therapy. MRI-guided focused ultrasound (MRgFUS) is now an approved noninvasive ablative treatment for ET that is effective and shows potential for continuing improvement. The first peripheral stimulation device for ET has also now been approved. This article reviews updates on the treatment of ET, encompassing pharmacologic agents in clinical trials, DBS, MRgFUS, and noninvasive stimulation therapies. Recent treatment advances and future directions of development show a great deal of promise for ET therapeutics.

Feasibility of Magnetic Resonance-Guided Focused Ultrasound Thalamotomy for Essential Tremor in the Setting of Prior Craniotomy.

Magnetic resonance imaging-guided focused ultrasound (MRgFUS) thalamotomy is a rapidly evolving therapy for the treatment of essential tremor. Although the skull is a major determinant of the delivery of acoustic energy to the target, how the presence of a prior craniotomy must be accounted for during lesioning is unclear. To demonstrate novel application of this therapeutic option in a patient with a history of prior craniotomies for unrelated intracranial pathologies. A 55-yr-old man with a history of right frontal craniotomy for resection of a colloid cyst underwent a left ventrointermedius nucleus thalamotomy through MRgFUS. The prior craniotomy flap was not excluded in the treatment plan; however, all bony defects and hardware were marked as "no-pass" regions. Clinical outcomes were collected at the 6-mo follow-up. Transducer elements whose acoustic paths would have been altered by the craniotomy defect were turned off. Sonications reaching lesional temperatures of up to 56°C were successfully delivered. The procedure was well-tolerated, without any persistent intra-ablation or postablation adverse effects. The presence of a lesion was confirmed on MRI, which was associated with a significant reduction in the patient's tremor that was sustained at the 6-mo follow-up. This case demonstrates the safety and efficacy of MRgFUS thalamotomy in a patient with prior craniotomies and highlights our strategy for acoustic lesioning in this setting.

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.