Mechanical characterization of brain tissue: experimental techniques, human testing considerations, and perspectives

Understanding the mechanical behavior of brain tissue is crucial for advancing both fundamental neuroscience and clinical applications. Yet, accurately measuring these properties remains challenging due to the brain's unique mechanical attributes and complex anatomical structures. This review provides a comprehensive overview of commonly used techniques for characterizing brain tissue mechanical properties, covering both invasive methods-such as atomic force microscopy, indentation, axial mechanical testing, and oscillatory shear testing-and noninvasive approaches like magnetic resonance elastography and ultrasound elastography. Each technique is evaluated in terms of working principles, applicability, representative studies, and experimental limitations. We further summarize existing publications that have used these techniques to measure human brain tissue mechanical properties. With a primary focus on invasive studies, we systematically compare their sample preparation, testing conditions, reported mechanical parameters, and modeling strategies. Key sensitivity factors influencing testing outcomes (e.g., sample size, anatomical location, strain rate, temperature, conditioning, and post-mortem interval) are also discussed. Additionally, selected noninvasive studies are reviewed to assess their potential for in vivo characterization. A comparative discussion between invasive and noninvasive methods, as well as in vivo versus ex vivo testing, is included. This review aims to offer practical guidance for researchers and clinicians in selecting appropriate mechanical testing approaches and contributes a curated dataset to support constitutive modeling of human brain tissue. STATEMENT OF SIGNIFICANCE: Accurate characterization of brain tissue mechanics is essential for both neurological research and the development of predictive biomechanical models. This review synthesizes current experimental approaches used in brain mechanical testing-spanning both invasive and noninvasive methods-with a focus on their principles, applications, and limitations. We further systematically compile and analyze a comprehensive set of invasive studies-supplemented by representative noninvasive reports-on human brain tissue mechanical properties. The collected dataset offers valuable support for constitutive modeling. Additionally, we discuss key factors affecting testing outcomes, offering practical insights to guide the design and interpretation of future brain mechanical research.