MRgFUS has just been made available for the 1.7 million Parkinson's disease patients in China. Despite its non-invasive and rapid therapeutic advantages for involuntary tremor, some concerns have emerged about outcomes variability, non-specificity, and side-effects, as little is known about its impact on the long-term plasticity of brain structure. We sought to dissect the characteristics of long-term changes in brain structure caused by MRgFUS lesion and explored potential biological mechanisms. One-year multimodal imaging follow-ups were conducted for nine tremor-dominant Parkinson's disease patients undergoing unilateral MRgFUS thalamotomy. A structural connectivity map was generated for each patient to analyze dynamic changes in brain structure. The human brain transcriptome was extracted and spatially registered for connectivity vulnerability. Genetic functional enrichment analysis was performed and further clarified using in vivo emission computed tomography data. MRgFUS not only abolished tremors but also significantly disrupted the brain network topology. Network-based statistics identified a U-shape MRgFUS-sensitive subnetwork reflective of hand tremor recovery and surgical process, accompanied by relevant cerebral blood flow and gray matter alteration. Using human brain gene expression data, we observed that dopaminergic signatures were responsible for the preferential vulnerability associated with these architectural alterations. Additional PET/SPECT data not only validated these gene signatures, but also suggested that structural alteration was significantly correlated with D1 and D2 receptors, DAT, and F-DOPA measures. There was a long-term dynamic loop between structural alteration and dopaminergic signature for MRgFUS thalamotomy, which may be closely related to the long-term improvements in clinical 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.

Purpose: To investigate the efficacy of the integration of functional magnetic resonance imaging and diffusion-tensor imaging tractography data into CyberKnife radiosurgery for intracranial tumor management. Materials and Methods: Functional neuroimaging, anatomical magnetic resonance imaging, and computed tomography images of patients with brain lesions in critical areas were acquired before radiosurgery. The acquired data sets were coregistered using the MIM image fusion software module and then were imported into the CyberKnife Robotic Radiosurgery System (Multiplan 4.0.2) for delineating the target, organs at risk, and possible nearby functionally relevant cortical and subcortical areas. Radiation dose distributions with and without the functionally relevant cortical and subcortical areas into the optimization process were developed and compared. Results: There were significant differences between the treatment plans with and without the functionally relevant cortical and subcortical areas into the optimization process. An average 22.71% reduction in the maximum dose to functional areas was observed. No neurological complication due to radiation damage was observed in the follow-up period. Conclusion: The functional neuroimaging could be easily and reliably integrated into the CyberKnife treatment planning. Consideration of functional structures and fiber tracts during treatment planning could clinically reduce the radiation doses to these critical structures, thereby preserving its unique function of brain.

[18F]ML-10 is a novel apoptosis radiotracer for positron emission tomography (PET). We assess the apoptosis response of intracranial tumor early after CyberKnife (CK) treatment by [18F]ML-10 PET imaging. 29 human subjects (30 lesions), diagnosed with intracranial tumors, underwent CK treatment at 14–24 Gy in 1–3 fractions, had [18F]ML-10 positron emission tomography/computed tomography (PET/CT) before (pre-CK) and 48 hours after (post-CK) CK treatment. Magnetic resonance imaging (MRI) scans were taken before and 8 weeks after CK treatment. Voxel-based analysis was used for the imaging analysis. Heterogeneous changes of apoptosis in tumors before and after treatment were observed on voxel-based analysis of PET images. A positive correlation was observed between the change in radioactivity (X) and subsequent tumor volume (Y) (r=0.862, p<0.05), with a regression equation of Y=1.018∗X−0.016. Malignant tumors tend to be more sensitive to CK treatment, but the treatment outcome is not affected by pre-CK apoptotic status of tumor cells; [18F]ML-10 PET imaging could be taken as an assessment 48 h after CK treatment.

Objective: To evaluate the efficacy and safety of hypofractionated stereotactic radiotherapy using CyberKnife for high volume cavernous sinus cavernous hemangiomas. Materials and Methods: We collected data from 12 patients with high volume cavernous sinus cavernous hemangiomas treated with hypofractionated stereotactic radiotherapy using CyberKnife in our institute, including 2 men and 10 women/female child, aged 4 to 60 years. Initial tumor volumes ranged from 11.8 to 96.6 cm³ with a median of 24.3 cm³. Irradiation doses were 19.5 Gy with 3 fractions in 2 patients, 21 Gy with 3 fractions in 8 patients, 25 Gy with 5 fractions in 1 patient, and 30 Gy with 3 fractions in 1 patient. We used 109 to 155 beams during treatment, and target volumes reached over 95% of the prescribed dose. Follow-up ranged from 3 to 54 months. We evaluated the efficacy and safety of the CyberKnife system based on changes in the diagnostic images and involved cranial nerves or symptoms. Results: Of the 12 patients, 11 were followed for 3 to 54 months with a mean follow-up of 16.3 months; 1 patient was lost to in-person follow-up. Lesion volumes in the followed 11 patients were calculated after fractionated radiotherapy. All tumor volumes decreased (28.6%-94.1%) and symptoms improved (including blurred vision, visual field defects, diplopia, headaches, and facial numbness) after therapy. Postoperative magnetic resonance images revealed a tumor volume range of 2.8 to 41.0 cm³ (median, 6.5 cm³), significantly lower compared with the pretreatment range of 11.8 to 70.1 cm³ (median, 24.3 cm³; T = 0.00, P = .003 < .05). A single patient experienced radiotherapy-related cerebral edema, which resolved after 5 days of mannitol and dexamethasone. Conclusions: Based on the current results, though preliminary, hypofractionated stereotactic radiotherapy using CyberKnife is an effective and safe alternative for high volume cavernous sinus cavernous hemangiomas and is the recommended primary treatment in high-risk patients with this condition.