Ultrasound imaging and therapeutics have been separately advancing over the past century but
not necessarily in harmony with one another. Despite the fact that ultrasound imaging was
invented after therapeutic ultrasound, the former is ubiquitous while the latter is only recently
crossing to the clinic for treatment of disease such as essential tremors and prostate cancer.
The brain is not exception: transcranial ultrasound has been used extensively for the detection
of stroke or hemorrhage while therapeutic ultrasound has been translated to the clinic mainly
with MRI guidance. This plenary will focus on using these two powerful modalities of ultrasound
first separately for imaging the brain with super-resolution, flow and/or elasticity imaging before
and after treatment with focused ultrasound (FUS) for either drug delivery or neuromodulation
and then in combination, for the theranostic transcranial application in conjunction with
microbubbles.
Treatment of neurological diseases has been at the forefront of medical research for more than
a century with limited success due partly to the blood-brain barrier (BBB) that impedes both
delivery and biodistribution of the drug delivered. Focused ulltrasound methodologies in
conjunction with systemically administered microbubbles have been shown capable of
transcranially and transiently opening the BBB over the past two decades. More recently, those
efforts have resulted into clinical translation in a variety of brain diseases such as brain tumors
and neurodegenerative disease such as Alzheimer’s (AD) and Parkinson’s disease. Findings
will be shown in preclinical studies in mice for the treatment of AD through immunomodulation
and treatment of PD using protein and gene delivery. The findings of two clinical studies will
also be reported. In the first clinical study, five AD patients underwent FUS with microbubbles
with successful BBB opening in their prefrontal cortex while 60% exhibited amyloid reduction in
the sonicated hemisphere. In the second clinical study, four diffuse intrinsic pontine glioma
(DIPG) subjects underwent BBB opening similar procedure with successful BBB opening in the
pons in conjunction with drug delivery. Our group has also been studying the noninvasive
stimulation and inhibition of the central and peripheral nervous systems in live animals. In the
brain, we have shown that focused ultrasound is capable of noninvasively eliciting motor and
sensory responses when distinct brain regions are targeted. In the periphery, when the
ultrasound beam is focused on the sciatic nerve in vivo, the thigh muscle is activated and
muscle twitches can be induced at low ultrasonic intensities while the same twitches can be
inhibited at higher intensities due to associated temperature rise that inhibits nerve firing.
Cellular and fiber responses in excised tissue have confirmed the live animal responses.
Applications in magnetogenetics will also be presented.