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Focused Ultrasound Neuromodulation of the Hypothalamus

Focused Ultrasound Neuromodulation of the Hypothalamus. Alexander Korb, Ph.D. Mentor: Alexander Bystritsky , M.D., Ph.D. Background. Hypothalamus is important in obesity and diabetes Target for insulin Center for appetite and satiety Deep brain stimulation (DBS) of hypothalamus

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Focused Ultrasound Neuromodulation of the Hypothalamus

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  1. Focused Ultrasound Neuromodulation of the Hypothalamus Alexander Korb, Ph.D. Mentor: Alexander Bystritsky, M.D., Ph.D

  2. Background • Hypothalamus is important in obesity and diabetes • Target for insulin • Center for appetite and satiety • Deep brain stimulation (DBS) of hypothalamus • Stimulation of lateral hypothalamus led to weight loss in rats • Indirect 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

  3. Objective • Develop a non-invasive neuromodulation system that can safely and accurately target the hypothalamus

  4. Neuromodulation • Deep 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

  5. LIFUP • High-frequency pressure waves • Focused mechanical energy • Demonstrated neuromodulation in rats and rabbits ) ) ) ) Transducer Tyler et al, 2008; Tufail et al 2010; Min et al, 2011; Yoo et al, 2011

  6. 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 ) ) )

  7. Results

  8. Challenges with Transcranial US • Skull absorbs energy • Skull changes shape of beam focus • Skull changes location of beam focus • Invisible beam X Ultrasound

  9. For Use in Humans • Accurately target deep brain structures • Visualize beam focus • Ensure patient safety • Monitor temperature ) ) ) ) Transducer

  10. Targeting • Magnetic resonance – acoustic radiation force imaging (MR-ARFI) • Force of US displaces tissue Kaye et al, 2010

  11. MR-ARFI Pulse Sequence Z Y X ADC RF Ultrasound Magnets Time

  12. MR-Thermometry • Proton spin is proportional to temperature • Temperature changes visible as phase differences • Standard fast spin echo pulse sequence

  13. Conclusions • LIFUP 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.

  14. Thank You Thanks to the Friedman Diabetes Institute for their generous support of this project

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