Magnetic resonance imaging and mathematical modeling of progressive formalin fixation of the human brain

The temporal magnetic resonance (MR) appearance of human brain tissue during formalin fixation was measured and modeled using a diffusion mathematical model of formalin fixation. Coronal MR images of three human brains before formalin fixation and at multiple time points thereafter were acquired. T1 relaxation, T2 relaxation, water apparent diffusion coefficient (ADC), and proton density (PD) maps were calculated. The size of a light “formalin band” region, visible in T1 weighted images, was compared to a mathematical model of diffusive mass transfer of formalin into the brain. T1 relaxation, T2 relaxation, and PD all decreased, in both gray and white matter, as formalin fixation progressed. The ADC remained more or less constant. The location of the inner boundary of the formalin band followed a time course consistent with the steepest formalin concentration gradient in the mathematical model. Based on the diffusion model, the brain is not completely saturated in formalin until after 14.8 weeks of formalin immersion and, based on the observed changes in T1, T2, and PD, fixation is not complete until after 5.4 weeks. During fixation, the ongoing attenuation of T1 relaxation, T2 relaxation, and PD must be taken into consideration when performing postmortem MRI studies. Magn Reson Med 54:324–332, 2005. © 2005 Wiley‐Liss, Inc.

[1]  F. Barkhof,et al.  Axonal loss in multiple sclerosis lesions: Magnetic resonance imaging insights into substrates of disability , 1999, Annals of neurology.

[2]  P Kapeller,et al.  Histopathologic analysis of foci of signal loss on gradient-echo T2*-weighted MR images in patients with spontaneous intracerebral hemorrhage: evidence of microangiopathy-related microbleeds. , 1999, AJNR. American journal of neuroradiology.

[3]  N. Fujita,et al.  Degeneration of the Pyramidal Tracts in Patients with Amyotrophic Lateral Sclerosis , 1997, Journal of neuroimaging : official journal of the American Society of Neuroimaging.

[4]  I. Vavasour,et al.  A pathology-MRI study of the short-T2 component in formalin-fixed multiple sclerosis brain , 2000, Neurology.

[5]  I. Wilkinson,et al.  The assessment of postmortem brain volume; a comparison of stereological and planimetric methodologies , 1999, Neuroradiology.

[6]  Lars-Olof Wahlund,et al.  Postmortem MRI and Histopathology of White Matter Changes in Alzheimer Brains , 2002, Dementia and Geriatric Cognitive Disorders.

[7]  F. Barkhof,et al.  Histopathologic correlate of hypointense lesions on T1-weighted spin-echo MRI in multiple sclerosis , 1998, Neurology.

[8]  R L Kamman,et al.  Changes of relaxation times T1 and T2 in rat tissues after biopsy and fixation. , 1985, Magnetic resonance imaging.

[9]  M. Castillo,et al.  Postmortem MR imaging of the brains of patients with AIDS. , 1997, Neuroimaging clinics of North America.

[10]  F Barkhof,et al.  Post-mortem MRI-guided sampling of multiple sclerosis brain lesions: increased yield of active demyelinating and (p)reactive lesions. , 2001, Brain : a journal of neurology.

[11]  F. Barkhof,et al.  Pre- and post-mortem MR imaging of unsuspected multiple sclerosis in a patient with Alzheimer's disease , 1993, Journal of the Neurological Sciences.

[12]  E P du Boulay,et al.  Histopathology of multiple sclerosis lesions detected by magnetic resonance imaging in unfixed postmortem central nervous system tissue. , 1991, Brain : a journal of neurology.

[13]  M. Bobinski,et al.  The histological validation of post mortem magnetic resonance imaging-determined hippocampal volume in Alzheimer's disease , 1999, Neuroscience.

[14]  Weili Lin,et al.  Current Protocols in Magnetic Resonance Imaging , 2001 .

[15]  I. Wilkinson,et al.  Postmortem MR imaging of the fetal and stillborn central nervous system. , 2003, AJNR. American journal of neuroradiology.

[16]  P. Goldman-Rakic,et al.  Smaller frontal gray matter volume in postmortem schizophrenic brains. , 2002, The American journal of psychiatry.

[17]  Penny A. Gowland,et al.  T1: The Longitudinal Relaxation Time , 2004 .

[18]  H L Kundel,et al.  Nuclear magnetic resonance characteristics of fresh and fixed tissue: the effect of elapsed time. , 1983, Radiology.

[19]  G J Barker,et al.  Stereotactic co‐registration of magnetic resonance imaging and histopathology in post‐mortem multiple sclerosis brain , 2003, Neuropathology and applied neurobiology.

[20]  F. Barkhof,et al.  Cortical lesions in multiple sclerosis. , 1999, Brain : a journal of neurology.

[21]  T. Yoshiura,et al.  MR imaging of the mamillothalamic tract. , 1998, Radiology.

[22]  I. Wilkinson,et al.  Correlation of MRI and neuropathology in AIDS. , 1997, Journal of neurology, neurosurgery, and psychiatry.

[23]  P. Joseph,et al.  High-resolution MR of the spinal cord in humans and rats. , 1989, AJNR. American journal of neuroradiology.

[24]  K J Klose,et al.  High-resolution diffusion-weighted MR of fresh and fixed cat spinal cords: evaluation of diffusion coefficients and anisotropy. , 1997, AJNR. American journal of neuroradiology.

[25]  A. Blamire,et al.  Optimising Imaging Parameters for Post Mortem MR Imaging of the Human Brain , 1999, Acta radiologica.

[26]  U. Salvolini,et al.  Postmortem MRI as a useful tool for investigation of cerebral microbleeds. , 2003, Stroke.

[27]  E. C. Zachmanoglou,et al.  Introduction to partial differential equations with applications , 1976 .

[28]  V. Haughton,et al.  MR appearance of the internal architecture of Ammon's horn. , 1996, AJNR. American journal of neuroradiology.

[29]  Petra Schmalbrock,et al.  MR imaging visualization of the cerebral microvasculature: a comparison of live and postmortem studies at 8 T. , 2003, AJNR. American journal of neuroradiology.

[30]  T. Crow,et al.  Ventricular enlargement in schizophrenia: a primary change in the temporal lobe? , 2003, Schizophrenia Research.

[31]  Marc Dhenain,et al.  Senile plaques do not induce susceptibility effects in T 2*‐weighted MR microscopic images , 2002, NMR in biomedicine.

[32]  P. Morosan,et al.  Probabilistic Mapping and Volume Measurement of Human Primary Auditory Cortex , 2001, NeuroImage.

[33]  M. Symms,et al.  Hippocampal layers on high resolution magnetic resonance images: real or imaginary? , 1999, Journal of anatomy.

[34]  Sheng-Kwei Song,et al.  Relative indices of water diffusion anisotropy are equivalent in live and formalin‐fixed mouse brains , 2003, Magnetic resonance in medicine.

[35]  T. Okudera,et al.  Volumetric analysis of the germinal matrix and lateral ventricles performed using MR images of postmortem fetuses. , 2001, AJNR. American journal of neuroradiology.

[36]  L. Quan,et al.  Sudden death of an infant with 'an early epileptic encephalopathy'. , 2001, Forensic science international.

[37]  Joseph A Maldjian,et al.  Diffusion anisotropy in the corpus callosum. , 2002, AJNR. American journal of neuroradiology.

[38]  K. Zilles,et al.  Areas 3a, 3b, and 1 of Human Primary Somatosensory Cortex 2. Spatial Normalization to Standard Anatomical Space , 2000, NeuroImage.

[39]  G Macchi,et al.  An in vivo and post mortem MRI study in multiple sclerosis with pathological correlation. , 1992, Italian journal of neurological sciences.

[40]  M. Maier Quantitative MRI of the brain—measuring changes caused by disease , 2004 .