Biomechanical Characterization of Epileptic Brain for Surgical Planning of Intractable Epilepsy

ABSTRACT Neurological disorders, including epilepsy, often manifest with altered brain stiffness, particularly in affected regions. The complex relationship between the biomechanical and microstructural characteristics of epileptic brain (EB) is poorly understood and warrants comprehensive research. This study investigates the in vitro viscoelastic properties of surgically excised EB tissues ( S = 20) and marginal normal brain (NB) ( S = 10) from the same individuals diagnosed with varying epileptogenic substrates. The microstructural characterization including neuron density, myelin and collagen content was also performed. Additionally, in vivo magnetic resonance elastography (MRE) was conducted on one subject to complement the in vitro findings as a pilot investigation. EB exhibited significantly higher stiffness than NB (storage modulus : 6.49 3.83 kPa vs. 1.97 0.40 kPa; loss modulus : 1.53 0.93 kPa vs. 0.61 0.31 kPa; p = 0.001). Among pathological subtypes, mesial temporal sclerosis (MTS) tissues were the stiffest (: 8.42 4.05 kPa and : 1.95 1.03 kPa), while focal cortical dysplasia (FCD) tissues were the softest (: 2.56 0.45 kPa and : 0.83 0.41 kPa). Other etiologies fell between these extremes. Microstructural correlations revealed a strong positive relationship between stiffness and neuronal density ( r = 0.81), a moderate negative correlation with myelin content ( r = −0.52), and no significant association with collagen content ( r = 0.15), indicating that cellular composition, rather than extracellular matrix components, predominantly contributes tissue mechanics. The in vivo MRE findings in an FCD lesion (: 2.65 0.30 kPa; : 0.91 0.25 kPa) showed concordance with the in vitro measurement of specimen from same subject (: 2.50 0.41 kPa; : 0.47 0.36 kPa). A deeper understanding of the mechanical differences between EB and NB has implications for personalized surgical planning, the development of high‐fidelity computational models, and improved elastography and non‐rigid image registration algorithms.