Table 1.

Overview of clinical trials using FUS+MB for the treatment or diagnosis of CNS disease.

Clinical trial (NIH reference)	Clinical trial phase	Condition of interest	Study description & role of inflammation as modulator or side effect
NCT02343991 vi	Phase not applicable	Brain tumors	Evaluate whether FUS can increase passage of tumor-specific biomarkers into the vasculature, improving the quality of liquid biopsy [106]
NCT02253212 iv	Phase III	Glioblastoma (recurrent)	Evaluate BBB opening tolerated by patients before delivery of chemotherapeutics; discusses anticancer immune response in the context of other organ-specific cancers (e.g., breast cancer) and studies in other species (e.g., mouse models) in [107]
NCT02986932 ii	Phase I	Alzheimer’s disease	Reduction of pathological protein aggregate in AD; no mention of inflammation as modulator or in post-treatment evaluation [7]
NCT03321487 i	Phase not applicable	Amyotrophic lateral sclerosis	Evaluation of BBB opening in primary motor cortex; MRI imaging show transient disruption via gadolinium perfusion [6]; the authors reported no significant inflammation 30 days post-procedure.
NCT03551249 vii	Phase not applicable	Glioma	Establishing safety profile for patients using FUS+MB as first line of therapy (standard chemotherapy); no mention of inflammation as immunomodulator for glioma treatment.
NCT03608553 iii	Phase I	Parkinson’s disease dementia	Performed BBB opening in parieto-occipito-temporal regions of the patients’ brains; no adverse effects reported [8]; no mention of inflammation
NCT03616860 viii	Phase I	Glioma	Evaluating FUS+MB to increase quality of liquid biopsy via increasing tumor biomarker perfusion into vasculature through transient BBB opening [108]; no mention of inflammation as possible modulator
NCT03671889 v	Phase II	Alzheimer’s disease	Evaluation of focal, transient BBB opening in the hippocampus; found indications of perivenous blood-meningeal permeability post-barrier disruption which may be indicative of tissue healing process (in the context of inflammation) [100]
NCT03782194 ix	Phase not applicable	Anxiety, obsessive compulsive disorder, posttraumatic stress disorder	Investigate whether usage of FUS pulsation can influence amygdala function to improve emotion regulation
NCT04118764 x	Phase not applicable	Alzheimer’s disease	Prospective study done with non-human primates in which eosinophil count increased; low acoustic pressure leads to minimal inflammatory cell density [109]
NCT04370665 xi	Phase not applicable	Parkinson’s disease	Delivering imiglucerase using Exablate MRgFUS system and Definity to open the BBB; no mention of inflammation
NCT04526262 xii	Phase not applicable	Alzheimer’s disease	Evaluated plaque removal and cognitive functions post-FUS+MB treatment (repeated opening) [110]; no mention of inflammation specific to the study
NCT04620460 xiii	Phase not applicable	Schizophrenia	Investigate whether FUS pulsation can modulate cortical function; no mention of immunomodulation as mechanistic target
NCT04804709 xiv	Phase I	Progressive diffuse midline glioma (DMG)	Evaluate whether FUS+MB delivery of Panobinostat through transient BBB opening is safe (phase I); no discussion on immunomodulation as possible mechanism
NCT05089786 xv	Phase II	Treatment-resistant neurologic and psychiatric indications	To evaluate whether FUS can improve clinical measurements in neurological and psychiatric disorders; no discussion of inflammation