Focused Ultrasound Neuromodulation of the Hypothalamus

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

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rTra

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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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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