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NEUROLOGICAL APPLICATIONS OF FOCUSED ULTRASOUND · NEUROLOGICAL APPLICATIONS OF FOCUSED ULTRASOUND...
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NEUROLOGICAL APPLICATIONS OF FOCUSED ULTRASOUND
SHELDON JORDAN, M.D., F.A.A.N., DABPN, DABAM, DABCN, DABIPPUCLA DEPARTMENT OF NEUROLOGY, NEUROLOGICAL ASSOCIATES OF WEST LOS ANGELES
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DISCLOSURE
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DISCLOSURE
• Chief investigator Pfizer supported study for Tyrosine Kinase Inhibitors for treatment of Alzheimer’s and Parkinsons
• Chief investigator Focused Ultrasound study for delivery of Tyrosine Kinase Inhibitor to hippocampus
• Chief investigator Focused Ultrasound study for delivery of Tyrosine Kinase Inhibitor to Substantia Nigra
• Chief investigator autologous adipose derived stem cell injections for chronic migraine
• Chief investigator microbubble enhanced opening of blood brain barrier with focused ultrasound
• Consultant/collaborator BrainSonix
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NEUROLOGICAL APPLICATIONS OF FOCUSED ULTRASOUND
• Ablation
• Sonothrombolysis
• Drug delivery and opening blood brain barrier
• Neuromodulation
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FOCUSING SOUND
• Ear of Dionysius, Sicily, 367 B.C.E.
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FOCUSING SOUND
• Saint Paul Whispering Gallery,
London, 1711
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FOCUSING SOUND
• Megaphone
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WHAT IS ULTRASOUND?
Media College
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WHAT IS ULTRASOUND?
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WHAT IS ULTRASOUND?
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WHAT IS ULTRASOUND?
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WHAT IS ULTRASOUND?
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WHAT IS ULTRASOUND?
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WHAT IS ULTRASOUND? Electrical Energy transformed into ultrasound: PIEZOELECTIC EFFECT
Churchill Livingston, 2009
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WHAT IS ULTRASOUND?
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WHAT IS ULTRASOUND?
Churchill Livingston, 2009
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WHAT IS ULTRASOUND?
Churchill Livingston,2009
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WHAT IS ULTRASOUND?
Churchill Livingston, 2009
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WHAT IS ULTRASOUND?
Churchill Livingston, 2009
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WHAT ARE THE EFFECTS OF ULTRASOUND ON TISSUE?
• MECHANICAL
• THERMAL
• STIMULATION
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ULTRASOUND VS. SKULL AND BRAIN
• Reflection: Loss of penetrating waves, chance for reflection with standing waves and excess effects
• Refraction: Loss of precision targeting
• Absorption: Loss of penetrating waves, inadvertent scalp heating
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MRI GUIDED FOCUSED ULTRASOUND
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SOLUTIONS TO LIMITATIONS
• Single piezoelectric probe, single lens through acoustic window
• Multiple probe over entire skull with phase correction and monitoring (in MRI scanner)
• Hybrid (in and out of MRI scanner)
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SOLUTIONS FOR LIMITATIONS
• Standard Windows through skull
• Individualized Window assessment using MRI/MRA coordinates
• Re evaluation of power and temperature deposition limits
• Phase Correction with CT based data sets
• Accurate/real time temperature and mechanical monitoring
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APPLICATIONS
• Ablation, High Intensity Focused Ultrasound; tissue necrosis at center, penumbra of apoptotic effects
• Sonolysis; break up clot, potential for bleeding at frequencies less than one hertz
• drug and particulate delivery; increase blood flow, open tight junctions, possible increased transcellular migration
• Stimulation; release of synaptic vesicles or deformation of post synaptic channels
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MRI GUIDED FOCUSED ULTRASOUNDWITHMULTIPLE PROBES
2017
Fishman, et al, 2017
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MRI GUIDED FOCUSED ULTRASOUND
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MRI GUIDED FOCUSED ULTRASOUND
Lost Planet, 1953
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MRI GUIDED FOCUSED ULTRASOUND
2017
Kyriakou, et al, 2014
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MRI GUIDED FOCUSED ULTRASOUND
2017
Kyriakou, et al, 2014
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MRI GUIDED FOCUSED ULTRASOUND
2017
MRI-ARFI Acoustic Radiation Force Imaging
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MRI GUIDED FOCUSED ULTRASOUND
Wintermark, et al, 2014
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MRI GUIDED FOCUSED ULTRASOUND
Wintermark, et al, 2013
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MRI GUIDED FOCUSED ULTRASOUND
Hectors, et al, 2016
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MRI GUIDED FOCUSED ULTRASOUND
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MRI GUIDED FOCUSED ULTRASOUND
ELIAS, et al,NEJM, 2016
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MRI GUIDED FOCUSED ULTRASOUND FOR ESSENTIAL TREMOR
• Variable response effect and durability
• Substantial side effect rate particularly if done bilaterally
• Very expensive and demanding of resources
• Uncertain target localization from functional standpoint
• Limited to central brain targets
• Competes with DBS
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MRI GUIDED FOCUSED ULTRASOUND
COLUCCIA, et al,2014
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MRI GUIDED FOCUSED ULTRASOUND FOR TUMOR ABLATION
• Unable to treat larger tumors
• Able to target tumors limited to central/thalamic regions
• Competes with Laser, radiation and other modalities
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FOCUSED ULTRASOUND FOR SONOLYSIS
• Thrombus sonolysis
• Safe and effective at frequencies greater than 1 megahertz
• Hemorrhage at frequencies less than 1 megahertz due to greater energy, penetrance and standing waves
• Amyloid plaque lysis
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MRI GUIDED FOCUSED ULTRASOUND FOR DELIVERING MOLECULAR AGENTS, NANOPARTICLE AND CELLULAR AGENTS
• Open blood brain barrier, facilitate trans endothelial migration
• Interaction of mechanical power, penetration effects with lower frequencies
• Enhanced effects with microbubbles
• Greater sized particles, cells require lower frequency (penetration) and power with resultant bleed risk
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FOCUSED ULTRASOUNDOPENING OF BLOOD BRAIN BARRIER
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MRI GUIDED FOCUSEDULTRASOUND FOR DRUG AND CELL DELIVERY
Alternative strategy to forceful opening of BBB with high intensity ultrasound; instead use pulsed low intensity ultrasound (LIFUP) aimed at hippocampus for Alzheimer’s disease
Intrinsic or extrinsic neural stimulation would normally result in sufficient NVC
In Alzheimer’s there is loss of coupling; with neural activation there is insufficient blood flow
Insufficient blood flow is likely trigger of inflammatory cascade
Stem cells home to inflammatory cytokines with trans endothelial migration
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MRI GUIDED FOCUSED ULTRASOUND FOR STIMULATION
Monti, et al, Brain Stimulation, 2016
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THE END