🔊 1. Ultrasound Basics
Ultrasound = sound waves above 20,000 Hz (beyond human hearing).
FUS typically uses frequencies between 200 kHz to several MHz.
Ultrasound travels as longitudinal pressure waves through tissues, causing oscillations in the particles of the medium.
Just like light can be focused with a lens, ultrasound waves can be focused using:
Concave transducers (geometrical focusing)
Phased arrays (electronic focusing via time delays)
This concentrates the energy in a small focal zone (millimeter-sized), enabling precise targeting.
There are thermal and mechanical effects depending on intensity and duration:
🌡️ Thermal Effects (High-Intensity FUS) Absorption of ultrasound energy leads to tissue heating.
If temp > 60°C, it causes coagulative necrosis (e.g., in tumor ablation).
Acoustic cavitation: formation and collapse of microbubbles (in liquids or tissues with gas), which can:
Increase BBB permeability
Causes microstreaming and shear stress
Radiation force: ultrasound can push or displace tissue, used in neuromodulation or drug delivery.
MRgFUS (MRI-guided focused ultrasound) is used for:
Thalamotomy for essential tremor
Reversible BBB opening (for chemo delivery in glioblastoma)
Neuromodulation without thermal damage (low-intensity FUS)
Parameter Description
Frequency (f) Affects penetration and resolution Intensity (I) Power per unit area, determines heating/mechanics Focal length Distance from transducer to focus Beam width Size of focal zone, smaller = higher precision Duty cycle % of time the ultrasound is “on” Pulse repetition Relevant in pulsed FUS (for non-thermal effects)
🧠 CNS Anatomical Targets & Indications 1. Thalamus Target: Ventral intermediate nucleus (Vim) of the thalamus
Application:
🔹 Essential tremor
🔹 Parkinsonian tremor
Mechanism: High-intensity focused ultrasound (HIFU) causes thermocoagulative lesioning for tremor suppression.
Guidance: MRI-guided (MRgFUS)
2. Globus Pallidus Internus (GPi) Application:
🔹 Parkinson’s disease (dyskinesia, rigidity)
🔹 Dystonia
Mechanism: Lesioning via thermal ablation
3. Subthalamic Nucleus (STN) Application:
🔹 Advanced Parkinson’s disease
Note: Currently less used than Vim or GPi due to anatomical complexity and potential for side effects.
4. Anterior Limb of the Internal Capsule (ALIC) Application:
🔹 Obsessive-compulsive disorder (OCD)
🔹 Major depressive disorder (MDD)
Mechanism: Capsulotomy using FUS as a non-invasive psychiatric neurosurgical intervention.
5. Hippocampus Application:
🔹 Experimental seizure control in temporal lobe epilepsy
Mechanism: Lesioning or neuromodulation (research phase)
6. Brain Tumors & Metastases Targets: Variable — glioblastoma, meningioma, metastases
Application:
🔹 BBB opening for chemotherapy delivery
🔹 Thermal ablation of tumors (in selected cases)
Mechanism:
Reversible blood-brain barrier (BBB) disruption using microbubble-enhanced low-intensity FUS
Experimental direct ablation (only in accessible areas)
7. Brainstem / Pons / Cerebellum Application: Mostly experimental
🔹 Neuromodulation
🔹 Pain control (e.g., central post-stroke pain)
Challenge: Proximity to critical structures → requires very precise targeting
8. Spinal Cord (experimental) Research into neuromodulation of the dorsal columns or motor tracts
Challenging due to acoustic shadowing by vertebral bone and narrow intervertebral windows
🧬 Non-CNS Targets Prostate: Ablation for prostate cancer or BPH
Uterus: Fibroid treatment
Liver, kidney, pancreas: Tumor ablation
Bone metastases: Pain palliation
🧭 Summary Table Target Area FUS Application Mechanism Vim (Thalamus) Essential tremor, Parkinsonian tremor Lesioning GPi Parkinson’s, Dystonia Lesioning ALIC OCD, Depression Capsulotomy Tumor areas BBB opening, Ablation Cavitation / Thermal Hippocampus Epilepsy (research) Lesion / Modulation Spinal Cord Neuromodulation (research) Modulation
see MRgFUS
see High Intensity focused ultrasound.
Focused ultrasound is a unique noninvasive technique that can transiently disrupt the blood-brain barrier (BBB) and increase accumulation of drugs within targeted areas of the brain.
Arsiwala et al. summarized the current understanding of different types of targeted ultrasound mediated BBB/BTB disruption techniques. We also discuss influence of the tumor microenvironment on BBB opening, as well as the role of immunological response following disruption. Lastly, we highlight the gaps between evaluation of the parameters governing opening of the BBB/BTB. A deeper understanding of physical opening of the BBB/BTB and the biological effects following disruption can potentially enhance treatment strategies for patients with brain tumors 1).