Hypothetical applications of MR-guided focused ultrasound in central nervous system tuberculosis: blood-brain barrier disruption, granulomatous lesion modulation, targeted drug delivery, and immune microenvironment reprogramming.

Central nervous system tuberculosis (CNS-TB) comprises tuberculous meningitis (TBM), parenchymal tuberculomas, and spinal arachnoiditis. It accounts for 5% to 10% of extrapulmonary TB and is more common in immunocompromised individuals, particularly those with HIV. Despite early diagnosis and treatment, mortality remains high, exceeding 30% in TB meningitis, and, as a consequence, many survivors develop cognitive, motor, or visual deficits. Management has proven to be difficult due to the blood-brain barrier and blood-cerebrospinal fluid barrier, which limit drug penetration, especially in early or non-inflammatory stages. Even after disruption of these barriers owing to inflammation, drug delivery remains inconsistent and often fails to reach the required concentrations. Tuberculomas further compound this problem due to their granulomatous, avascular, and fibrotic architecture, which protects Mycobacterium tuberculosis from both host immunity and antibiotics. Magnetic resonance-guided focused ultrasound (MRgFUS) is an established, non-invasive neurosurgical technology that may offer a platform to transiently disrupt physiological barriers or modulate lesion structure using microbubble-mediated cavitation. Although MRgFUS is FDA-approved for movement disorders and under investigation in brain tumors, its application in CNS-TB remains entirely untested. Conceptually, MRgFUS could enhance drug delivery to protected CNS compartments, theoretically alter granulomatous architecture to improve antimicrobial penetration, and facilitate targeted delivery of immunomodulatory agents. This narrative and hypothesis-generating review explores the theoretical role of MRgFUS as an adjunctive strategy in CNS-TB, while explicitly acknowledging current evidence gaps and safety uncertainties.