To investigate the neural mechanism of Magnetic resonance-guided focused ultrasound (MRgFUS) Pallidothalamic Tractotomy in Parkinson's disease through multi-model MRI, and identify imaging biomarkers for triaging candidates and predicting the clinical outcomes.

Parkinson's disease (PD) is the second most progressive neurodegenerative disease with many motor and non-motor symptoms, which brings heavy burden to the family and the society.

MRgFUS pallidothalamic tractotomy allows to address all symptoms of PD without skull opening and with very limited tissue ablation, but with varying effectiveness. The unknown pathogenesis of PD has greatly contributed to this variance. Therefore, in order to optimize the clinical application of MRgFUS pallidothalamic tractotomy, it is important to reveal the pathogenesis of Parkinson's disease by using multiple modality MRI methods, and identify imaging biomarkers to triage suitable candidates and predict clinical outcomes.

Treatment scheme:

All patients will first receive uni- or bilateral MRgFUS PTT. As to bilateral interventions, the second one will take place at least 6 months after the first PTT. Patients with unilateral intervention will be followed to 1 year. Patients with bilateral interventions will be followed to 1 year after the second intervention. Baseline clinical demographics, Unified Parkinson Disease Rating Scale (UPDRS), treatment parameters (energy, power, duration time, temperature, target location) , associated adverse effects were recorded.

Imaging protocols:

T2; T2 Flair; DWI; ESWAN; MRS; 3D ASL 2.0s; 3D-T1; DTI; rs-functional MRI

Imaging evaluation:

1. Lesion appearance and volume are measured by T2, T2 Flair, DWI, ESWAN, 3D-T1;
2. ESWAN and MRS manifests the changes of iron deposition and metabolism, respectively;
3. ASL shows regional cerebral blood flow associated with the procedure;
4. DTI demonstrates the destruction of white matter integrity.
5. Rs-functional MRI reflects alterations of resting-state brain activity.

Treatment:

MRgFUS pallidothalamic tractotomy

Follow-up:

MRI + clinical evaluation: Baseline, 3-day, 1-week, 1-month, 3-months, 6-months,12-months

Inclusion Criteria:

1. Regardless of sex, aged 30 or above, hope to treat bilateral motor symptoms and receive the other side treatment plan at the 6th month;
2. Subjects are able and willing to give informed consent and can participate in whole study visits;
3. It was clinically diagnosed as Parkinson's disease and confirmed by functional neurosurgeons;
4. The subjects should respond to levodopa;
5. In the off-medication state, the subjects' MDS-UPDRS scores were 30 or more.

Exclusion Criteria:

1. The subjects scored 3 or more in the pull-back test;
2. Parkinson's disease symptoms were suspected as the side effects of antipsychotics;
3. severe cognitive impairment confirmed by neuropsychologists;
4. subjects with other neurodegenerative diseases;
5. Subjects with unstable mental illness, defined as active, uncontrolled depression, schizophrenia, delusions, hallucinations or suicide intention;
6. Pregnant or lactating women;
7. Subjects with alcohol or drug abuse;
8. Subjects with unstable heart condition or severe hypertension;
9. Subjects with a history of abnormal bleeding or clotting.

Patients with Parkinson's disease