Therapeutic ultrasound is older than ultrasound imaging and yet has not translated to the clinic until only recently. Focused ultrasound (FUS) has been shown to facilitate drug delivery through the opening of the blood-brain barrier (BBB). Protein and gene delivery will be shown in the neuroprotection and neurorestoration of the nigrostriatal pathway through the combined use of FUS and AAV-GDNF in an early-stage Parkinson’s disease (PD) mouse model. Our group has demonstrated that only the striatum that received a combination of AAV-GDNF and FUS exhibited protection against a subsequent MPTP insult while the mice with already existing and stable MPTP lesions exhibited signs of both behavioral and morphological amelioration following AAV-GDNF and FUS with up to 76% restoration, especially in the neuronal terminals. A second study will also be presented for the treatment of Alzheimer’s disease (AD) in a mouse model expressing both amyloid and tau. In this case, FUS targets the hippocampus and both amyloid and tau are shown to be reduced with behavioral working memory also improved in the FUS-treated group only. FUS has thus the capability of overcoming certain limitations of pharmacological agents that are incapable of permeating the BBB at clinically relevant dosages; thereby opening new avenues for disease-modifying strategies in undertreated neurodegenerative disorders such as PD and AD.
FUS can also affect brain cognition, either with but also without opening the BBB and merely exerting mechanical and/or thermal effects on the brain or peripheral nerves and driving neuronal modulation. Examples of lateralized motor and sensory responses will be shown in mice and improvement in motor and cognitive performance in non-human primates (NHP) will be shown as well as pain suppression in human subjects by targeting the median nerve.
Finally, FUS is used for ablation of tumors in the clinic and in this lecture, an elastographic technique developed by our group, Harmonic Motion Imaging, will be demonstrated in its capability of identifying the type, targeting and treating breast and pancreatic tumors while also monitoring and assessing the procedure before and after chemotherapy based on the change in the underlying tumor stiffness as a result of the treatment.
1. To understand the mechanisms of inducing neurorestoration through protein and gene delivery by opening the blood-brain barrier.
2. To understand the mechanisms of neuromodulation using therapeutic ultrasound in the brain and peripheral nerves.
3. To understand the imaging capabilities of monitoring elasticity changes in tumors to assess responses to chemotherapy and ultrasound ablation.