Focused Ultrasound for Parkinson's Disease

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Focused Ultrasound for Parkinson's Disease

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Focused Ultrasound for Parkinson's Disease

Overview

<table class="infobox infobox-therapeutic">
<tr>
<th class="infobox-header" colspan="2">Focused Ultrasound for Parkinson's Disease</th>
</tr>
<tr>
<td class="label">Target</td>
<td>UPDRS-III Improvement</td>
</tr>
<tr>
<td class="label">Vim (thalamotomy)</td>
<td>40-50%</td>
</tr>
<tr>
<td class="label">GPi (pallidotomy)</td>
<td>30-45%</td>
</tr>
<tr>
<td class="label">STN</td>
<td>35-50%</td>
</tr>
<tr>
<td class="label">Year</td>
<td>Indication</td>
</tr>
<tr>
<td class="label">2016</td>
<td>Essential Tremor</td>
</tr>
<tr>
<td class="label">2018</td>
<td>Tremor-dominant PD</td>
</tr>
<tr>
<td class="label">2021</td>
<td>Parkinson's disease tremor</td>
</tr>
<tr>
<td class="label">Complication</td>
<td>Frequency</td>
</tr>
<tr>
<td class="label">Transient numbness/tingling</td>
<td>10-15%</td>
</tr>
<tr>
<td class="label">Gait instability</td>
<td>5-10%</td>
</tr>
<tr>
<td class="label">Speech difficulties</td>
<td>3-8%</td>
</tr>
<tr>
<td class="label">Intracranial hemorrhage</td>
<td><1%</td>
</tr>
<tr>
<td class="label">Skin burn</td>
<td>Rare</td>
</tr>
<tr>
<td class="label">Feature</td>
<td>Focused Ultrasound</td>
</tr>
<tr>
<td class="label">Invasiveness</td>
<td>Non-invasive</td>
</tr>
<tr>
<td class="label">Implant</td>
<td>None</td>
</tr>
<tr>
<td class="label">Recovery</td>
<td>1-2 day

...

Focused Ultrasound for Parkinson's Disease

Overview

<table class="infobox infobox-therapeutic">
<tr>
<th class="infobox-header" colspan="2">Focused Ultrasound for Parkinson's Disease</th>
</tr>
<tr>
<td class="label">Target</td>
<td>UPDRS-III Improvement</td>
</tr>
<tr>
<td class="label">Vim (thalamotomy)</td>
<td>40-50%</td>
</tr>
<tr>
<td class="label">GPi (pallidotomy)</td>
<td>30-45%</td>
</tr>
<tr>
<td class="label">STN</td>
<td>35-50%</td>
</tr>
<tr>
<td class="label">Year</td>
<td>Indication</td>
</tr>
<tr>
<td class="label">2016</td>
<td>Essential Tremor</td>
</tr>
<tr>
<td class="label">2018</td>
<td>Tremor-dominant PD</td>
</tr>
<tr>
<td class="label">2021</td>
<td>Parkinson's disease tremor</td>
</tr>
<tr>
<td class="label">Complication</td>
<td>Frequency</td>
</tr>
<tr>
<td class="label">Transient numbness/tingling</td>
<td>10-15%</td>
</tr>
<tr>
<td class="label">Gait instability</td>
<td>5-10%</td>
</tr>
<tr>
<td class="label">Speech difficulties</td>
<td>3-8%</td>
</tr>
<tr>
<td class="label">Intracranial hemorrhage</td>
<td><1%</td>
</tr>
<tr>
<td class="label">Skin burn</td>
<td>Rare</td>
</tr>
<tr>
<td class="label">Feature</td>
<td>Focused Ultrasound</td>
</tr>
<tr>
<td class="label">Invasiveness</td>
<td>Non-invasive</td>
</tr>
<tr>
<td class="label">Implant</td>
<td>None</td>
</tr>
<tr>
<td class="label">Recovery</td>
<td>1-2 days</td>
</tr>
<tr>
<td class="label">Adjustability</td>
<td>Fixed lesion</td>
</tr>
<tr>
<td class="label">Reversibility</td>
<td>Permanent</td>
</tr>
<tr>
<td class="label">Bilateral treatment</td>
<td>Higher risk</td>
</tr>
<tr>
<td class="label">MRI compatibility</td>
<td>Yes</td>
</tr>
<tr>
<td class="label">Trial</td>
<td>Target</td>
</tr>
<tr>
<td class="label">NCT04021520</td>
<td>GPi FUS</td>
</tr>
<tr>
<td class="label">NCT03319485</td>
<td>STN FUS</td>
</tr>
<tr>
<td class="label">NCT04540670</td>
<td>BBB opening + GDNF</td>
</tr>
<tr>
<td class="label">NCT05331236</td>
<td>Bilateral FUS</td>
</tr>
</table>

Focused Ultrasound (FUS) is a non-invasive therapeutic technology that uses concentrated acoustic energy to treat neurological disorders, including Parkinson's disease (PD). By precisely targeting deep brain structures without surgical incision, FUS offers a groundbreaking alternative to traditional neurosurgical interventions. This page provides a comprehensive overview of FUS therapy for Parkinson's disease, covering mechanism of action, clinical evidence, regulatory status, target selection, outcomes, and comparison to other therapies. [@quality2020]

--- [@cognitive]

Mechanism of Action

Focused ultrasound works by delivering multiple overlapping ultrasound beams to a precise focal point within the brain. When these beams converge, they generate localized heating or mechanical effects that can be precisely controlled to achieve therapeutic outcomes. [@mrguided2017]

Physical Principles of Focused Ultrasound

The fundamental physics underlying FUS involves the conversion of acoustic energy into thermal energy at a precise focal point. Ultrasound waves are mechanical waves that propagate through biological tissues, and when concentrated at a specific location, they can induce various biological effects depending on the intensity and duration of exposure. [@future2020]

Key physical parameters include:

Frequency: Typically 650 kHz to 1 MHz for brain applications
Intensity: High-intensity (>1000 W/cm²) for ablation; low-intensity (<1000 W/cm²) for BBB opening
Duration: Seconds to minutes for ablation; minutes for BBB opening
Focal volume: Typically 2-10 mm in diameter

The ultrasound beam is focused using either a hemispherical transducer array (most common) or a lens system. Modern systems use hundreds to thousands of individual transducers arranged in a bowl configuration, each capable of being independently controlled for phase and amplitude. This phased array approach allows electronic steering of the focal point without moving the transducer.

Biological Effects of Thermal Ablation

When the temperature at the focal point reaches 54-60°C, protein denaturation occurs within seconds, leading to immediate and irreversible cell death through coagulative necrosis. The surrounding tissue experiences a temperature gradient, with temperatures falling rapidly outside the focal zone. This creates a well-defined lesion with a sharp transition between treated and normal tissue.

The thermal effects are monitored in real-time using magnetic resonance imaging (MRI) thermometry, which measures the proton resonance frequency shift to calculate temperature maps. This feedback allows the operator to precisely control the lesion size and shape, adjusting treatment parameters in real-time based on the observed thermal map.

Mechanical Effects and Cavitation

In addition to thermal effects, low-intensity ultrasound can produce mechanical effects through acoustic cavitation. When ultrasound interacts with microbubble contrast agents, the bubbles oscillate (stable cavitation) or collapse violently (inertial cavitation), producing mechanical stress on surrounding tissues.

This mechanical disruption can:

Temporarily open endothelial cell junctions in the blood-brain barrier
Enhance drug and gene delivery to targeted brain regions
Stimulate neuronal activity through mechanosensitive ion channels
Promote release of neurotrophic factors

The Role of MRI Guidance

Magnetic resonance imaging serves dual roles in FUS treatment:

Treatment planning: High-resolution anatomical imaging for precise target identification

Real-time thermometry: Temperature mapping during energy delivery

Post-treatment verification: Confirming lesion creation

The integration of MRI with FUS represents a major advancement over earlier ultrasound technologies, enabling unprecedented precision and safety for intracranial procedures.

High-Intensity Focused Ultrasound (HIFU) for Ablation

High-intensity focused ultrasound (HIFU) creates thermal ablation by raising the temperature at the target site to 54-60°C within seconds [1](https://doi.org/10.3171/2019.12.FOCUS19870). This thermal lesioning achieves similar effects to surgical lesioning procedures like thalamotomy or pallidotomy, but without any surgical opening of the skull.

The key advantages of HIFU include:

Real-time MR thermometry for precise temperature monitoring
Immediate feedback allowing immediate assessment of treatment effect
No implant required unlike deep brain stimulation
Minimal surrounding tissue damage due to precise focus

Low-Intensity Focused Ultrasound (LIFU) for BBB Opening

Low-intensity focused ultrasound, when combined with intravenous microbubble contrast agents, can temporarily open the blood-brain barrier (BBB) [2](https://doi.org/10.1001/jam Neurol.2019.3659). This technique uses mechanical effects from oscillating microbubbles to disrupt endothelial cell junctions, enabling delivery of therapeutic agents that would otherwise be blocked.

BBB opening with LIFU is being investigated for:

Delivery of neurotrophic factors (e.g., GDNF, BDNF)
Gene therapy vector delivery
Chemotherapeutic agent delivery for brain tumors
Enhanced immunotherapy for neurodegenerative diseases

Target Structures in Parkinson's Disease

The primary targets for FUS in PD are:

Ventral Intermediate Nucleus (Vim) of the thalamus - primary target for tremor

Globus Pallidus interna (GPi) - target for dyskinesias and motor symptoms

Subthalamic Nucleus (STN) - target for comprehensive motor symptom control

Clinical Evidence

Tremor-Dominant Parkinson's Disease

Multiple clinical trials have demonstrated the efficacy of FUS thalamotomy for tremor-dominant PD. A pivotal randomized controlled trial showed:

80-90% tremor reduction in the contralateral hand at 12 months [3](https://doi.org/10.1056/NEJMoa1600159)
Significant improvement in handwriting and activities of daily living
Durable effects maintained through 4-year follow-up [4](https://doi.org/10.3171/2020.1.FOCUS19840)

Motor Symptom Outcomes (UPDRS Scores)

The Unified Parkinson's Disease Rating Scale (UPDRS) Part III (motor examination) improvements vary by target:

Long-Term Follow-Up Data

Studies with 3-5 year follow-up demonstrate:

Sustained tremor suppression in most patients
No delayed neurological deficits from the lesion
Low rates of symptom recurrence requiring additional procedures

Non-Motor Symptom Effects

While primarily targeting motor symptoms, FUS treatment can affect non-motor features:

Some patients report improved sleep quality
Reduction in medication-related neuropsychiatric side effects
Potential for cognitive effects requiring further study

Quality of Life Improvements

Beyond motor scores, FUS treatment significantly impacts patient quality of life. Studies using the Parkinson's Disease Questionnaire-39 (PDQ-39) demonstrate:

Improved activities of daily living due to tremor reduction
Enhanced emotional well-being from reduced disability
Better social functioning from increased participation in community activities
Reduced caregiver burden as patients regain independence

Special Populations

Elderly Patients
FUS offers particular advantages for elderly patients who may be poor surgical candidates:

No general anesthesia required (procedures performed under conscious sedation)
Reduced risk of infection compared to implantable devices
Quick recovery time minimizes hospitalization risks
Studies show efficacy and safety in patients over 75 years

Patients on Anticoagulation
Patients who cannot discontinue anticoagulation therapy (common in PD with cardiovascular comorbidities) may still be candidates for FUS, as the procedure does not require surgical incision or significant bleeding risk.

Regulatory Status

FDA Approvals

The FDA has approved focused ultrasound for several neurological indications:

Insurance Coverage

Coverage varies by insurer:

Medicare covers FUS for essential tremor and tremor-dominant PD
Private insurers increasingly covering based on medical necessity
Pre-authorization typically required

Target Selection

Ventral Intermediate Nucleus (Vim)

The Vim is the primary target for treating tremor in PD [5](https://pubmed.ncbi.nlm.nih.gov/33481043/):

Located in the thalamus
Part of the cerebellar receiving area
Hyperactive in tremor states
Ablation interrupts tremor circuit

Patient selection criteria:

Tremor-dominant PD (not akinesia-predominant)
Inadequate response to medications
Intolerant or unsuitable for DBS
Unilateral symptoms (FUS is typically unilateral)

Globus Pallidus Interna (GPi)

GPi targeting addresses dyskinesias and motor fluctuations [6](https://doi.org/10.3171/2019.2.FOCUS18472):

Output nucleus of the basal ganglia
Overactivity leads to bradykinesia and rigidity
Ablation reduces dyskinesias from medication overuse

Advantages:

Effective for medication-induced dyskinesias
May reduce motor fluctuations
Lower risk of cognitive side effects

Subthalamic Nucleus (STN)

STN is the most common target for DBS but less commonly targeted with FUS [7](https://doi.org/10.1007/s00701-020-04589-w):

Central hub in the basal ganglia circuit
Controls for comprehensive motor symptom relief
More challenging to target precisely

Considerations:

Higher risk of side effects (speech, cognition)
Requires extremely precise targeting
More research needed on FUS-STN outcomes

Decision Framework for Target Selection

Choosing the optimal FUS target requires careful consideration of multiple factors:

Predominant symptoms: Tremor vs. dyskinesias vs. rigidity/bradykinesia

Disease stage: Early vs. advanced PD

Medication response: Levodopa-responsive vs. non-responsive features

Symptom laterality: Unilateral vs. bilateral

Cognitive status: Normal vs. impaired

Patient preferences: Invasive vs. non-invasive tolerance

The decision tree typically follows:

Tremor-dominant → Vim thalamotomy
Dyskinesias/dopa-induced fluctuations → GPi pallidotomy
Comprehensive motor control needed → Consider STN or DBS

Outcomes and Complications

Clinical Outcomes

Positive outcomes include:

Immediate tremor suppression (often visible during treatment)
Reduced medication requirements
Improved quality of life measures
Quick recovery (typically 1-2 days hospitalization)

Adverse Events and Complications

Reported complications include:

Risk Factors for Complications

Advanced age (>75 years) - increased risk
Bilateral procedures - higher complication rates
Target location - proximity to critical structures
Lesion size - larger lesions correlate with more side effects

Patient Selection and Contraindications

Ideal candidates for FUS:

Age 65-85 years
Tremor-dominant or dyskinesia-dominant PD
Responsive to levodopa (for GPi targeting)
Intolerant or unsuitable for DBS
Unilateral symptoms primarily
No significant cognitive impairment
Able to lie still for 2-4 hours

Relative contraindications:

Significant cognitive impairment (MMSE <24)
Severe depression or psychiatric comorbidities
Brain atrophy >15 mm
Metallic implants incompatible with MRI
Uncorrected coagulopathy
Major medical comorbidities

Comparison to Deep Brain Stimulation

Advantages of FUS over DBS

Limitations of FUS

Unilateral only - bilateral FUS carries higher risk

No adaptive stimulation - cannot adjust to symptom fluctuations

Permanent lesion - cannot be reversed if side effects occur

Limited target options - smaller treatment volume

Skull characteristics - skull density affects treatment feasibility

Learning curve - requires specialized expertise

When to Choose FUS vs DBS

Consider FUS when:

Patient unsuitable for surgery (anticoagulation, medical comorbidities)
Patient prefers non-invasive option
Tremor-dominant with inadequate medication response
Intolerant to DBS hardware

Consider DBS when:

Bilateral treatment needed
Require adaptive/stimulus-responsive therapy
Younger patients (long-term adjustability important)
Need to modulate stimulation over time

Companies and Clinical Trials

Insightec

Insightec is the leading company in neurological FUS:

Exablate Neuro - FDA-approved device for movement disorders
Over 100 treatment centers worldwide
Extensive clinical trial program
Ongoing research in Alzheimer's disease and brain tumors

Treatment Procedure Overview

Understanding the FUS procedure helps in patient counseling:

Pre-treatment evaluation (1-2 weeks before):

Neurological examination and motor scoring
MRI brain scan for targeting
Cognitive and psychiatric assessment
Medical clearance for anesthesia

Treatment day:

Head shaved and frame attached to skull
Stereotactic frame provides precise coordinate system
Patient positioned in MRI scanner
Low-power test sonications to verify targeting
Full-power sonications to create lesion
Real-time temperature monitoring throughout
Total procedure time: 2-4 hours

Post-treatment:

Neurological examination immediately after
MRI to confirm lesion
Overnight observation typically required
Discharge within 24-48 hours
Follow-up at 1 week, 1 month, 3 months, 6 months, then annually

Clinical Trials (Active and Recent)

Emerging Applications

Research is exploring:

Dementia - amyloid and tau reduction
Epilepsy - seizure focus ablation
Brain tumors - enhanced drug delivery
Psychiatric disorders - OCD, depression

Therapeutic Approaches

[Deep Brain Stimulation (DBS)](/therapeutics/deep-brain-stimulation) - Surgical treatment alternative
[Deep Brain Stimulation for Parkinson's Disease](/therapeutics/deep-brain-stimulation-parkinson) - DBS specifically for PD
[Adaptive Deep Brain Stimulation (DBS) Technology](/technologies/adaptive-dbs) - Advanced DBS systems

Brain Structures

[Subthalamic Nucleus (STN) Neurons](/cell-types/subthalamic-nucleus) - Target for movement disorders
[Globus Pallidus Neurons](/cell-types/globus-pallidus-neurons) - GPi target structure
[Globus Pallidus Internus (GPi) Neurons](/cell-types/globus-pallidus-internus) - Specific GPi cell type

[Essential Tremor](/diseases/essential-tremor) - First FDA-approved FUS indication

Future Directions

The field of focused ultrasound for Parkinson's disease continues to evolve:

Bilateral FUS - Reducing risk for bilateral procedures

Combined approaches - FUS with drug delivery or gene therapy

Improved targeting - Enhanced MRI guidance and real-time feedback

New targets - Exploring novel brain structures

Repetitive treatments - Multiple sessions for progressive diseases

External Links

[PubMed](https://pubmed.ncbi.nlm.nih.gov/)
[KEGG Pathways](https://www.genome.jp/kegg/pathway.html)

References

[Unknown, Focused Ultrasound Thalamotomy for Parkinson's Disease: Technical Considerations (2019)](https://doi.org/10.3171/2019.12.FOCUS19870)

[DOI:10.1001/jam](https://doi.org/10.1001/jam)

[Unknown, MRI-Guided Focused Ultrasound Thalamotomy for Tremor (n.d.)](https://doi.org/10.1056/NEJMoa1600159)

[Unknown, Long-Term Outcomes of Focused Ultrasound Thalamotomy (2020)](https://doi.org/10.3171/2020.1.FOCUS19840)

[Unknown, Vim Thalamus: Anatomy and Target for Movement Disorders (n.d.)](https://pubmed.ncbi.nlm.nih.gov/33481043/)

[Unknown, Pallidotomy with Focused Ultrasound for Dyskinesias (2019)](https://doi.org/10.3171/2019.2.FOCUS18472)

[Unknown, Subthalamic Nucleus Targeting with Focused Ultrasound (n.d.)](https://doi.org/10.1007/s00701-020-04589-w)

Unknown, Insightec Exablate Neuro for Parkinson's Disease (n.d.)

Unknown, FDA Approval of Focused Ultrasound for Essential Tremor (n.d.)

[Unknown, Comparative Effectiveness of FUS vs DBS (2020)](https://doi.org/10.3171/2020.4.FOCUS20156)

[Unknown, Safety Profile of Focused Ultrasound in Movement Disorders (2019)](https://doi.org/10.3171/2019.9.FOCUS19535)

[Unknown, Quality of Life Outcomes After FUS Thalamotomy (2020)](https://doi.org/10.1016/j.parkreldis.2020.02.018)

[Unknown, Cognitive Effects of Thalamic FUS (n.d.)](https://doi.org/10.1002/mdc3.12956)

[Unknown, MR-Guided Focused Ultrasound: Technical Review (2017)](https://doi.org/10.3171/2017.9.FOCUS17381)

[Unknown, Future Applications of Focused Ultrasound in Neurology (2020)](https://doi.org/10.3171/2020.5.FOCUS20312)

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Incoming

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Outgoing

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📗 Cite This Artifact

Focused Ultrasound for Parkinson's Disease

Focused Ultrasound for Parkinson's Disease

Overview

Focused Ultrasound for Parkinson's Disease

Overview

Mechanism of Action

Physical Principles of Focused Ultrasound

Biological Effects of Thermal Ablation

Mechanical Effects and Cavitation

The Role of MRI Guidance

High-Intensity Focused Ultrasound (HIFU) for Ablation

Low-Intensity Focused Ultrasound (LIFU) for BBB Opening

Target Structures in Parkinson's Disease

Clinical Evidence

Tremor-Dominant Parkinson's Disease

Motor Symptom Outcomes (UPDRS Scores)

Long-Term Follow-Up Data

Non-Motor Symptom Effects

Quality of Life Improvements

Special Populations

Regulatory Status

FDA Approvals

Insurance Coverage

Target Selection

Ventral Intermediate Nucleus (Vim)

Globus Pallidus Interna (GPi)

Subthalamic Nucleus (STN)

Decision Framework for Target Selection

Outcomes and Complications

Clinical Outcomes

Adverse Events and Complications

Risk Factors for Complications

Patient Selection and Contraindications

Comparison to Deep Brain Stimulation

Advantages of FUS over DBS

Limitations of FUS

When to Choose FUS vs DBS

Companies and Clinical Trials

Insightec

Treatment Procedure Overview

Clinical Trials (Active and Recent)

Emerging Applications

Cross-Links to Related Pages

Therapeutic Approaches

Brain Structures

Related Movement Disorders

Future Directions

See Also

External Links

References

Pathway Diagram

💬 Discussion