title: Effects of formalin fixation and temperature on MR relaxation times in the human brain.
abstract: Post-mortem MRI of the brain is increasingly applied in neuroscience for a better understanding of the contrast mechanisms of disease induced tissue changes. However, the influence of chemical processes caused by formalin fixation and differences in temperature may hamper the comparability with results from in vivo MRI. In this study we investigated how formalin fixation and temperature affect T1, T2 and T2* relaxation times of brain tissue. Fixation effects were examined with respect to changes in water content and crosslinking. Relaxometry was performed in brain slices from five deceased subjects at different temperatures. All measurements were repeated after 190 days of formaldehyde immersion. The water content of unfixed and fixed tissue was determined using the wet-to-dry ratio following drying. Protein weight was determined with sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). Fixation caused a strong decrease of all relaxation times, the strongest effect being seen on T1, with a reduction of up to 76%. The temperature coefficient of T1 was lower in the fixed than unfixed tissue, which was in contrast to T2, where an increase of the temperature coefficient was observed following fixation. The reduction of the water content after fixation was in the range of 1-6% and thus not sufficient to explain the changes in relaxation time. Results from SDS-PAGE indicated a strong increase of the protein size above 260 kDa in all brain structures examined. Our results suggest that crosslinking induced changes of the macromolecular matrix are responsible for T1 shortening and a decreased temperature dependency. The relaxation times provided in this work should allow optimization of post-mortem MRI protocols for the brain.
authors.affiliation: Department of Neurology, Medical University of Graz, Austria.
authors.forename: Christoph
authors.initials: C
authors.lastname: Birkl
authors.affiliation: Department of Neurology, Medical University of Graz, Austria.|MGH Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Harvard Medical School, Boston, MA, USA.
authors.forename: Christian
authors.initials: C
authors.lastname: Langkammer
authors.affiliation: Department of Neuropathology, Institute of Pathology, Medical University of Graz, Austria.
authors.forename: Nicole
authors.initials: N
authors.lastname: Golob-Schwarzl
authors.affiliation: Department of Neuropathology, Institute of Pathology, Medical University of Graz, Austria.
authors.forename: Marlene
authors.initials: M
authors.lastname: Leoni
authors.affiliation: Department of Neuropathology, Institute of Pathology, Medical University of Graz, Austria.
authors.forename: Johannes
authors.initials: J
authors.lastname: Haybaeck
authors.affiliation: Institute of Chemistry, Analytical Chemistry, University of Graz, Austria.
authors.forename: Walter
authors.initials: W
authors.lastname: Goessler
authors.affiliation: Department of Neurology, Medical University of Graz, Austria.
authors.forename: Franz
authors.initials: F
authors.lastname: Fazekas
authors.affiliation: Department of Neurology, Medical University of Graz, Austria.
authors.forename: Stefan
authors.initials: S
authors.lastname: Ropele
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001921:Brain / Q000000981:diagnostic imaging*; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D005557:Formaldehyde / Q000737:chemistry*; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D013696:Temperature; D013997:Time Factors; D016707:Tissue Fixation / Q000379:methods*; D014867:Water
chemical_list: D014867:Water; D005557:Formaldehyde
keywords: MRI; formalin fixation; human brain; post-mortem MRI; relaxation times; temperature