140 likes | 352 Views
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
E N D
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 • 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
Objective • Develop a non-invasive neuromodulation system that can safely and accurately target the hypothalamus
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
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
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 ) ) )
Challenges with Transcranial US • Skull absorbs energy • Skull changes shape of beam focus • Skull changes location of beam focus • Invisible beam X Ultrasound
For Use in Humans • Accurately target deep brain structures • Visualize beam focus • Ensure patient safety • Monitor temperature ) ) ) ) Transducer
Targeting • Magnetic resonance – acoustic radiation force imaging (MR-ARFI) • Force of US displaces tissue Kaye et al, 2010
MR-ARFI Pulse Sequence Z Y X ADC RF Ultrasound Magnets Time
MR-Thermometry • Proton spin is proportional to temperature • Temperature changes visible as phase differences • Standard fast spin echo pulse sequence
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.
Thank You Thanks to the Friedman Diabetes Institute for their generous support of this project