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.