Non-invasive therapy of brain disorders with focused ultrasound : from animal experiments to clinical transfer

Youliana Younan 1
1 POM - Physique des Ondes pour la Médecine et la Biologie
INSERM - Institut National de la Santé et de la Recherche Médicale : U979, Institut Langevin ondes et images
Abstract : The work presented in this thesis investigates novel modalities to guide Transcranial Magnetic Resonance guided Focused Ultrasound (TcMRgFUS). TcMRgFUS is an emerging and promising non-invasive technique for the treatment of neurological disorders, such as essential tremor or Parkinsonian tremor. A novel Magnetic Resonance Acoustic Radiation Force Imaging (MRARFI) has been used to image the location of the ultrasonic beam produced by a preclinical prototype: an accelerated 2D spin-echo MR ARFI pulse sequence has been introduced to generate undistorted ultrasound-induced displacement maps in ex vivo veal brains with minimum energy deposition. We then investigated direct effects of the ultrasonic beam on brain activity by conducting in vivo ultrasonic neuromodulation, similarly to what is currently achieved with transcranial magnetic stimulation (TMS) but with the millimetric targeting capabilities of the ultrasound. Experiments have been first conducted in an anesthetized rat model to investigate the motor threshold. Numerical simulations have shown that the acoustic pattern in the rat head is affected by reverberations and that special care must be taken when relating acoustic parameters to neurostimulation effects, especially at a low frequency and for small animals. Finally, for the first time, we used low intensity FUS stimulation to causally modulate behavior in an awake nonhuman primate brain. We showed that the latency of an anti-saccade task was delayed significantly in the presence of ultrasonic beam focused in the Frontal Eye Field. Sham experiments did not show any significant change in the latencies.
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Youliana Younan. Non-invasive therapy of brain disorders with focused ultrasound : from animal experiments to clinical transfer. Other [cond-mat.other]. Université Pierre et Marie Curie - Paris VI, 2014. English. ⟨NNT : 2014PA066101⟩. ⟨tel-01066142⟩

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