Download
targeting and safety monitoring for lifup in first human trials n.
Skip this Video
Loading SlideShow in 5 Seconds..
Targeting and Safety Monitoring for LIFUP in First Human Trials PowerPoint Presentation
Download Presentation
Targeting and Safety Monitoring for LIFUP in First Human Trials

Targeting and Safety Monitoring for LIFUP in First Human Trials

92 Views Download Presentation
Download Presentation

Targeting and Safety Monitoring for LIFUP in First Human Trials

- - - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - - -
Presentation Transcript

  1. Targeting and Safety Monitoring for LIFUP in First Human Trials Alexander Korb, PhD Mentor: Alexander Bystritsky, M.D., Ph.D

  2. Objective Develop a non-invasive neuromodulation system that can safely and accurately target the hypothalamus )))) ) Transducer

  3. Outline • Background • Technology • Experiments • Next Steps

  4. Background • Hypothalamus • Target for insulin • Center for appetite and satiety • Deep Brain Stimulation (DBS) of lateral hypothalamus • Weight loss in rats • Indirect results in humans show potential • Obici et al, 2002; Bernardis and Bellinger, 1996; Halpern et al, 2008; Sani et al, 2007; Torres et al 2011

  5. DBS = X

  6. Alternative to DBS • Low-Intensity Ultrasound Pulsations (LIFUP) • Highly focused • Non-invasive • Safe ) ) ) ) )

  7. Outline • Background • Technology • Experiments • Next Steps

  8. Ultrasound • Traditional US Imaging • Reflect acoustic energy • Focused US • Absorb acoustic energy • Increased intensity to a small region ) ) ) ) ) ) ) ) ) ) Transducer ) ) ) ) ) Transducer

  9. LIFUP Neuromodulation • Hippocampal excitation • Motor activation • Suppression of visual response • Suppression of seizure activity Tyler et al, 2008; Tufail et al 2010; Min et al, 2011; Yoo et al, 2011

  10. Challenges for Human LIFUP • Skull absorbs energy • Skull changes shape of beam focus • Skull changes location of beam focus • Invisible beam X Ultrasound

  11. Goals of Experiments • Assess feasibility • Develop targeting • Test safety

  12. Outline • Background • Technology • Experiments • Next Steps

  13. Feasibility in Large Mammalian Brain • Anesthetized mini-pig • Prepared skull • Targeted hypothalamus with stereotactic frame ) ) ) Mulgaonkar et al 2012

  14. Hypothalamic Stimulation P

  15. Targeting with Thermometry • Continuous US to cause heating • Proton resonant frequency is proportional to temperature 9cm 20s 40s 60s 80s 100s 120s 140s 160s Δ0.36°C Δ0°C FUS ON 9cm FUS OFF

  16. Skull Heating During LIFUP • Near FDA limit for diagnostic US • Only mild heating even after 5 minutes

  17. Skull Heating During CW US • 60s of continuous US • 13.4W/cm2 Ispta

  18. Goals of Experiments • Assess feasibility • Develop targeting • Test safety ✓ ✓ ✓

  19. Conclusions • LIFUP can accomplish neuromodulation in deep brain structures • MR-Thermometry can be used for targeting • LIFUP is ready for human testing

  20. Outline • Background • Technology • Experiments • Next Steps

  21. First Human Experiments • 10 patients with temporal lobe epilepsy • Concurrent LIFUP and fMRI • Outcomes: • Absence of histological damage • Neuromodulation • Changes in epileptic activity • Changes in seizure frequency

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