Brain stiffens post mortem

Alterations in brain rheology are increasingly recognized as a diagnostic marker for various neurological conditions. Magnetic resonance elastography now allows us to assess brain rheology repeatably, reproducibly, and non-invasively in vivo. Recent elastography studies suggest that brain stiffness decreases one percent per year during normal aging, and is significantly reduced in Alzheimer’s disease and multiple sclerosis. While existing studies successfully compare brain stiffnesses across different populations, they fail to provide insight into changes within the same brain. Here we characterize rheological alterations in one and the same brain under extreme metabolic changes: alive and dead. Strikingly, the storage and loss moduli of the cerebrum increased by 26% and 60% within only three minutes post mortem and continued to increase by 40% and 103% within 45 minutes. Immediate post mortem stiffening displayed pronounced regional variations; it was largest in the corpus callosum and smallest in the brainstem. We postulate that post mortem stiffening is a manifestation of alterations in polarization, oxidation, perfusion, and metabolism immediately after death. Our results suggest that the stiffness of our brain–unlike any other organ–is a dynamic property that is highly sensitive to the metabolic environment Our findings emphasize the importance of characterizing brain tissue in vivo and question the relevance of ex vivo brain tissue testing as a whole. Knowing the true stiffness of the living brain has important consequences in diagnosing neurological conditions, planning neurosurgical procedures, and modeling the brain’s response to high impact loading.

[1]  Thibault P. Prevost,et al.  Dynamic mechanical response of brain tissue in indentation in vivo, in situ and in vitro. , 2011, Acta biomaterialia.

[2]  P. Asbach,et al.  Noninvasive assessment of the rheological behavior of human organs using multifrequency MR elastography: a study of brain and liver viscoelasticity , 2007, Physics in medicine and biology.

[3]  van der Tpj Tom Sande,et al.  Mechanical properties of brain tissue by indentation: interregional variation. , 2010, Journal of the mechanical behavior of biomedical materials.

[4]  Tsuyoshi Murata,et al.  {m , 1934, ACML.

[5]  Dagmar Krefting,et al.  The Influence of Physiological Aging and Atrophy on Brain Viscoelastic Properties in Humans , 2011, PloS one.

[6]  C. Jack,et al.  Decreased brain stiffness in Alzheimer's disease determined by magnetic resonance elastography , 2011, Journal of magnetic resonance imaging : JMRI.

[7]  E. Kuhl,et al.  Mechanics of the brain: perspectives, challenges, and opportunities , 2015, Biomechanics and Modeling in Mechanobiology.

[8]  E. H. Clayton,et al.  Quantitative imaging methods for the development and validation of brain biomechanics models. , 2012, Annual review of biomedical engineering.

[9]  Ellen Kuhl,et al.  The mechanical importance of myelination in the central nervous system. , 2017, Journal of the mechanical behavior of biomedical materials.

[10]  Karl J. Friston,et al.  Statistical parametric mapping , 2013 .

[11]  M. Nedergaard,et al.  Drowning stars: reassessing the role of astrocytes in brain edema , 2014, Trends in Neurosciences.

[12]  S. Eaton,et al.  Bridging the gap: large animal models in neurodegenerative research , 2017, Mammalian Genome.

[13]  Dieter Klatt,et al.  Non‐invasive measurement of brain viscoelasticity using magnetic resonance elastography , 2008, NMR in biomedicine.

[14]  Armando Manduca,et al.  Review of MR elastography applications and recent developments , 2012, Journal of magnetic resonance imaging : JMRI.

[15]  E. Kuhl,et al.  Viscoelastic parameter identification of human brain tissue. , 2017, Journal of the mechanical behavior of biomedical materials.

[16]  Huan Wang,et al.  Local mechanical properties of white matter structures in the human brain , 2013, NeuroImage.

[17]  Gorjan Alagic,et al.  #p , 2019, Quantum information & computation.

[18]  L. Taber,et al.  Axons pull on the brain, but tension does not drive cortical folding. , 2010, Journal of biomechanical engineering.

[19]  Dagmar Krefting,et al.  Brain Viscoelasticity Alteration in Chronic-Progressive Multiple Sclerosis , 2012, PloS one.

[20]  B. MacVicar,et al.  The Cellular Mechanisms of Neuronal Swelling Underlying Cytotoxic Edema , 2015, Cell.

[21]  R. Ehman,et al.  Magnetic resonance elastography , 1996, Nature Medicine.

[22]  P V Bayly,et al.  Viscoelastic properties of the ferret brain measured in vivo at multiple frequencies by magnetic resonance elastography. , 2013, Journal of Biomechanics.

[23]  Curtis L. Johnson,et al.  Magnetic resonance elastography (MRE) of the human brain: technique, findings and clinical applications , 2016, Physics in medicine and biology.

[24]  John D. Joannopoulos,et al.  An animal-to-human scaling law for blast-induced traumatic brain injury risk assessment , 2014, Proceedings of the National Academy of Sciences.

[25]  David F. Moore,et al.  In silico investigation of intracranial blast mitigation with relevance to military traumatic brain injury , 2010, Proceedings of the National Academy of Sciences.

[26]  Jochen Guck,et al.  Mechanics in neuronal development and repair. , 2013, Annual review of biomedical engineering.

[27]  Dieter Klatt,et al.  The impact of aging and gender on brain viscoelasticity , 2009, NeuroImage.

[28]  Ellen Kuhl,et al.  Magnetic resonance elastography of the brain: A comparison between pigs and humans. , 2018, Journal of the mechanical behavior of biomedical materials.

[29]  Jochen Guck,et al.  Viscoelastic properties of individual glial cells and neurons in the CNS , 2006, Proceedings of the National Academy of Sciences.

[30]  Rémy Willinger,et al.  Assessment of in vivo and post-mortem mechanical behavior of brain tissue using magnetic resonance elastography. , 2008, Journal of biomechanics.

[31]  A. Constantinesco,et al.  Fifty years of brain tissue mechanical testing: from in vitro to in vivo investigations. , 2010, Biorheology.

[32]  Richard L. Ehman,et al.  MR elastography of the brain and its application in neurological diseases , 2017, NeuroImage.

[33]  Ellen Kuhl,et al.  Mechanics of the mitral valve , 2013, Biomechanics and modeling in mechanobiology.

[34]  Ellen Kuhl,et al.  A critical review, an in vivo parameter identification, and the effect of prestrain , 2013 .

[35]  J. Tsuruda,et al.  Cytotoxic brain edema: assessment with diffusion-weighted MR imaging. , 1992, Radiology.

[36]  Rémi Souchon,et al.  Brain palpation from physiological vibrations using MRI , 2015, Proceedings of the National Academy of Sciences.

[37]  Clifford R. Jack,et al.  Measuring the effects of aging and sex on regional brain stiffness with MR elastography in healthy older adults , 2015, NeuroImage.

[38]  K D Paulsen,et al.  Viscoelastic power law parameters of in vivo human brain estimated by MR elastography. , 2017, Journal of the mechanical behavior of biomedical materials.

[39]  Guy M. McKhann,et al.  Regional mechanical properties of human brain tissue for computational models of traumatic brain injury. , 2017, Acta biomaterialia.

[40]  R L Ehman,et al.  Tissue characterization using magnetic resonance elastography: preliminary results. , 2000, Physics in medicine and biology.

[41]  E. Kuhl,et al.  Rheological characterization of human brain tissue. , 2017, Acta biomaterialia.

[42]  Arno Klein,et al.  Evaluation of 14 nonlinear deformation algorithms applied to human brain MRI registration , 2009, NeuroImage.

[43]  O. Ciccarelli,et al.  Nonconventional MRI and microstructural cerebral changes in multiple sclerosis , 2015, Nature Reviews Neurology.

[44]  Curtis L. Johnson,et al.  Magnetic resonance elastography for examining developmental changes in the mechanical properties of the brain , 2017, Developmental Cognitive Neuroscience.

[45]  A. Gefen,et al.  Are in vivo and in situ brain tissues mechanically similar? , 2004, Journal of biomechanics.

[46]  M. Prange,et al.  Regional, directional, and age-dependent properties of the brain undergoing large deformation. , 2002, Journal of biomechanical engineering.

[47]  C. Jack,et al.  Measuring the Characteristic Topography of Brain Stiffness with Magnetic Resonance Elastography , 2013, PLoS ONE.

[48]  Clifford R. Jack,et al.  Magnetic resonance elastography of the brain , 2008, NeuroImage.

[49]  A. Manduca,et al.  Magnetic resonance elastography by direct visualization of propagating acoustic strain waves. , 1995, Science.

[50]  Rjh Rudy Cloots,et al.  Multi-scale mechanics of traumatic brain injury: predicting axonal strains from head loads , 2013, Biomechanics and modeling in mechanobiology.

[51]  Richard L Ehman,et al.  MR Elastography Demonstrates Unique Regional Brain Stiffness Patterns in Dementias. , 2017, AJR. American journal of roentgenology.

[52]  Philip V Bayly,et al.  Measurement of the dynamic shear modulus of mouse brain tissue in vivo by magnetic resonance elastography. , 2008, Journal of biomechanical engineering.

[53]  Ellen Kuhl,et al.  The Incompatibility of Living Systems: Characterizing Growth-Induced Incompatibilities in Expanded Skin , 2015, Annals of Biomedical Engineering.

[54]  Barclay Morrison,et al.  A detailed viscoelastic characterization of the P17 and adult rat brain. , 2011, Journal of neurotrauma.

[55]  W. Hayes,et al.  A mathematical analysis for indentation tests of articular cartilage. , 1972, Journal of biomechanics.

[56]  B. Morrison,et al.  Dynamic, regional mechanical properties of the porcine brain: indentation in the coronal plane. , 2011, Journal of biomechanical engineering.

[57]  D. Dini,et al.  On the characterization of the heterogeneous mechanical response of human brain tissue , 2016, Biomechanics and Modeling in Mechanobiology.

[58]  R. Willinger,et al.  Shear Properties of Brain Tissue over a Frequency Range Relevant for Automotive Impact Situations: New Experimental Results. , 2004, Stapp car crash journal.

[59]  D. Le Bihan,et al.  Water diffusion in brain cortex closely tracks underlying neuronal activity , 2013, Proceedings of the National Academy of Sciences.

[60]  Edgar Santos,et al.  Radial, spiral and reverberating waves of spreading depolarization occur in the gyrencephalic brain , 2014, NeuroImage.

[61]  M. D. Del Bigio,et al.  Simultaneous determination of mechanical properties and physiologic parameters in living rat brain , 2009, Biomechanics and modeling in mechanobiology.

[62]  S. Kirov,et al.  Persistent astroglial swelling accompanies rapid reversible dendritic injury during stroke‐induced spreading depolarizations , 2012, Glia.

[63]  E. Kuhl,et al.  Mechanical properties of gray and white matter brain tissue by indentation. , 2015, Journal of the mechanical behavior of biomedical materials.

[64]  Rémy Willinger,et al.  Magnetic resonance elastography compared with rotational rheometry for in vitro brain tissue viscoelasticity measurement , 2007, Magnetic Resonance Materials in Physics, Biology and Medicine.

[65]  R. Ehman,et al.  Magnetic resonance elastography: A review , 2010, Clinical anatomy.

[66]  Alain Goriely,et al.  Stress Singularities in Swelling Soft Solids. , 2016, Physical review letters.

[67]  Jane Mummery,et al.  Regional , 2019, M/C Journal.

[68]  Ralph Sinkus,et al.  Demyelination reduces brain parenchymal stiffness quantified in vivo by magnetic resonance elastography , 2012, Proceedings of the National Academy of Sciences.

[69]  C. Birkl,et al.  Mechanical characterization of human brain tissue. , 2017, Acta biomaterialia.

[70]  P V Bayly,et al.  Frequency-dependent viscoelastic parameters of mouse brain tissue estimated by MR elastography , 2011, Physics in Medicine and Biology.

[71]  Aref Samadi-Dooki,et al.  A combined experimental, modeling, and computational approach to interpret the viscoelastic response of the white matter brain tissue during indentation. , 2018, Journal of the mechanical behavior of biomedical materials.

[72]  Jochen Guck,et al.  Mechanical difference between white and gray matter in the rat cerebellum measured by scanning force microscopy. , 2010, Journal of biomechanics.

[73]  Yan Li,et al.  Mechanical Properties of Porcine Brain Tissue in the Coronal Plane: Interregional Variations of the Corona Radiata , 2015, Annals of Biomedical Engineering.

[74]  J. F. Greenleaf,et al.  Magnetic resonance elastography: Non-invasive mapping of tissue elasticity , 2001, Medical Image Anal..

[75]  Curtis L. Johnson,et al.  The Relationship of Three-Dimensional Human Skull Motion to Brain Tissue Deformation in Magnetic Resonance Elastography Studies. , 2017, Journal of biomechanical engineering.

[76]  Barclay Morrison,et al.  Non-ideal effects in indentation testing of soft tissues , 2014, Biomechanics and modeling in mechanobiology.

[77]  Andrea Bergmann,et al.  Statistical Parametric Mapping The Analysis Of Functional Brain Images , 2016 .

[78]  Clifford R. Jack,et al.  Regional brain stiffness changes across the Alzheimer's disease spectrum☆ , 2015, NeuroImage: Clinical.

[79]  K Miller,et al.  Mechanical properties of brain tissue in-vivo: experiment and computer simulation. , 2000, Journal of biomechanics.

[80]  Andreas Meisel,et al.  Sugar for the brain: the role of glucose in physiological and pathological brain function , 2013, Trends in Neurosciences.

[81]  R T Cotton,et al.  Development of a geometrically accurate and adaptable finite element head model for impact simulation: the Naval Research Laboratory–Simpleware Head Model , 2016, Computer methods in biomechanics and biomedical engineering.

[82]  G. G. Stokes "J." , 1890, The New Yale Book of Quotations.

[83]  A. Lindblad,et al.  Persistent , 2020, Definitions.

[84]  R L Ehman,et al.  Complex‐valued stiffness reconstruction for magnetic resonance elastography by algebraic inversion of the differential equation , 2001, Magnetic resonance in medicine.

[85]  D. Kleinfeld,et al.  Fluctuating and sensory-induced vasodynamics in rodent cortex extend arteriole capacity , 2011, Proceedings of the National Academy of Sciences.

[86]  G. Genin,et al.  Measurements of mechanical anisotropy in brain tissue and implications for transversely isotropic material models of white matter. , 2013, Journal of the mechanical behavior of biomedical materials.

[87]  E Kuhl,et al.  Brain stiffness increases with myelin content. , 2016, Acta biomaterialia.

[88]  Aref Samadi-Dooki,et al.  An Indirect Indentation Method for Evaluating the Linear Viscoelastic Properties of the Brain Tissue. , 2017, Journal of biomechanical engineering.

[89]  Curtis L. Johnson,et al.  Observation of direction-dependent mechanical properties in the human brain with multi-excitation MR elastography. , 2016, Journal of the mechanical behavior of biomedical materials.