Implications of sonobiopsy in clinical settings. (A) By opening
the blood-brain barrier (BBB) and releasing proteins from the brain into the
circulation, sonobiopsy can enrich plasma with brain-derived pathologic
protein species. By simply collecting blood samples before and after
sonications, sonobiopsy enables temporally controlled liquid biopsy and
detection of changes in circulating pathologic protein species and other
biomarkers after focused ultrasound. (B) Sonobiopsy can allow
spatially resolved liquid biopsy. This can, in turn, be used for targeted
BBB opening in brain areas with high protein deposits on molecular imaging
(eg, tau or amyloid PET imaging). Sonobiopsy of these brain areas could shed
light on the dominant pathogenic subtypes in heavily involved brain areas.
In addition, the release of abnormal specific protein species can be
colocalized to the brain regions showing the greatest metabolic, structural,
or microstructural deficits. This can help identify the main culprits in
pathogenesis of various neurodegenerative disorders. (C)
Sonobiopsy can be readily integrated into focused ultrasound–induced
BBB opening clinical trials to allow monitoring of treatment response by
assessing changes in brain-derived pathogenic proteins. BBB = blood-brain
barrier, BM = biomarker concentration in plasma, CNS = central nervous
system, FUS = focused ultrasound.