Plasma glial fibrillary acidic protein as a biomarker of acute focal brain injury after high-intensity focused ultrasound thalamotomy

The validation of brain injury biomarkers has encountered challenges such as the absence of pre-insult measurements, variability in injury timing and location, and inter-individual differences. In this study, we addressed these limitations by using magnetic resonance-guided high-intensity focused ultrasound (MRgHIFU) thalamotomy to assess plasma biomarker changes after an acute focal brain injury. This prospective study included 30 essential tremor and tremor-dominant Parkinson's disease patients undergoing MRgHIFU thalamotomy at a single academic institution. Blood samples were collected at three specific time points: pre-procedure, 1-h post-procedure, and 48 h post-procedure. Plasma levels of glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), amyloid beta (Aβ40 and Aβ42) and phosphorylated tau 181 (pTau-181) were measured using the quanterix single molecule arrays assay. GFAP levels were significantly increased at 48 h post-MRgHIFU in all patients with a thalamotomy lesion. GFAP levels at 48 h were highly sensitive (89.7%) and specific (96.6%) in detecting the presence of a lesion with a cut-off value of 216.2 pg/ml. NfL, Aβ40 and Aβ42, also showed statistically significant increases post-procedure but were less robust than GFAP. No changes were observed in pTau-181 levels post-MRgHIFU. Plasma GFAP has shown great promise as a sensitive and reliable biomarker for detecting acute brain injury after MRgHIFU thalamotomy. Its significant elevation following the procedure highlights its potential as a diagnostic tool for acute focal brain injuries, such as stroke. Further studies with additional time points are essential to validate the injury cut-off identified in this study and to assess its broader clinical utility for early detection of focal brain lesions.