Focused Ultrasound Neuromodulation of the
HypothalamusAlexander Korb, Ph.D.
Mentor: Alexander Bystritsky, M.D., Ph.D
BackgroundHypothalamus is important in obesity and
diabetesTarget for insulin Center for appetite and satiety
Deep brain stimulation (DBS) of hypothalamusStimulation of lateral hypothalamus led to weight loss
in ratsIndirect observations of DBS in humans show potential
for hypothalamic stimulation to lead to weight loss
Obici et al, 2002; Bernardis and Bellinger, 1996; Halpern et al, 2008; Sani et al, 2007; Torres et al 2011
Objective
Develop a non-invasive neuromodulation system that can safely and accurately target the hypothalamus
NeuromodulationDeep Brain Stimulation (DBS)
Successfully targeted hypothalamus to reduce obesity Highly focused Requires invasive brain surgery
Transcranial Magnetic Stimulation (TMS) Non-invasive Large focal area
Low-intensity Focused Ultrasound Pulsations (LIFUP) Non-invasive Highly focused
LIFUPHigh-frequency pressure waves
Focused mechanical energy
Demonstrated neuromodulation in rats and rabbits
Tra
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uce
rTra
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uce
r ) ) ) ) Tyler et al, 2008; Tufail et al 2010; Min et al, 2011; Yoo et al, 2011
Modulating Hypothlamic Activity
Anesthetized mini-pig
Removed upper plate of skull
Polished lower plate of skull Similar thickness to human
temporal bone
Focused US on hypothalamus using stereotactic frame
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Results
Challenges with Transcranial US
Skull absorbs energy
Skull changes shape of beam focus
Skull changes location of beam focus
Invisible beam
UltrasoundX
For Use in HumansAccurately target deep brain structures
Visualize beam focus
Ensure patient safetyMonitor temperature
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rTra
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TargetingMagnetic resonance – acoustic radiation force
imaging (MR-ARFI)Force of US displaces tissue
Kaye et al, 2010
MR-ARFI Pulse SequenceZ
Y
X
A
DC
R
F
Mag
nets
Time
Ultrasound
MR-ThermometryProton spin is proportional to temperature
Temperature changes visible as phase differences
Standard fast spin echo pulse sequence
ConclusionsLIFUP can accomplish neuromodulation in the
hypothalamus
MR-ARFI may be able to guide LIFUP to the appropriate target
MR-Thermometry can be used to detect potentially harmful temperature changes
LIFUP is almost ready for human testing.
Thank YouThanks to the Friedman Diabetes Institute for their generous support of this project