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      Quantitative Ex Vivo MRI Changes due to Progressive Formalin Fixation in Whole Human Brain Specimens: Longitudinal Characterization of Diffusion, Relaxometry, and Myelin Water Fraction Measurements at 3T

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          Abstract

          Purpose

          Postmortem MRI can be used to reveal important pathologies and establish radiology–pathology correlations. However, quantitative MRI values are altered by tissue fixation. Therefore, the purpose of this study was to investigate time-dependent effects of formalin fixation on MRI relaxometry (T 1 and T 2), diffusion tensor imaging (fractional anisotropy, FA; and mean diffusivity, MD), and myelin water fraction (MWF) measurements throughout intact human brain specimens.

          Methods

          Two whole, neurologically-healthy human brains were immersed in 10% formalin solution and scanned at 13 time points between 0 and 1,032 h. Whole-brain maps of longitudinal (T 1) and transverse (T 2) relaxation times, FA, MD, and MWF were generated at each time point to illustrate spatiotemporal changes, and region-of-interest analyses were then performed in eight brain structures to quantify temporal changes with progressive fixation.

          Results

          Although neither of the diffusion measures (FA nor MD) showed significant changes as a function of formalin fixation time, both T 1 and T 2-relaxation times significantly decreased, and MWF estimates significantly increased with progressive fixation until (and likely beyond) our final measurements were taken at 1,032 h.

          Conclusion

          These results suggest that T 1-relaxation, T 2-relaxation and MWF estimates must be performed quite early in the fixation process to avoid formalin-induced changes compared to in vivo values; and furthermore, that different ex vivo scans within an experiment must be acquired at consistent (albeit still early) fixation intervals to avoid fixative-related differences between samples. Conversely, ex vivo diffusion measures (FA and MD) appear to depend more on other factors (e.g., pulse sequence optimization, sample temperature, etc.).

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          Most cited references46

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          Computing Large Deformation Metric Mappings via Geodesic Flows of Diffeomorphisms

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            In vivo visualization of myelin water in brain by magnetic resonance.

            We exploit the intrinsic difference in magnetic resonance spin-spin relaxation time, T2, between water associated with myelin sheaths and water in other central nervous system tissue in order to measure myelin water content within any region of an image or to generate indirectly a myelin map of the brain. In normal volunteers, myelin water maps give the expected myelin distribution. In multiple sclerosis patients, lesions exhibit different myelin water contents providing insight into the demyelination process unavailable from conventional magnetic resonance images. In vivo myelin measurement has important applications in the clinical management of multiple sclerosis and other white matter diseases.
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              Chemical and physical basics of routine formaldehyde fixation

              Formaldehyde is the widely employed fixative that has been studied for decades. The chemistry of fixation has been studied widely since the early 20th century. However, very few studies have been focused on the actual physics/chemistry aspect of process of this fixation. This article attempts to explain the chemistry of formaldehyde fixation and also to study the physical aspects involved in the fixation. The factors involved in the fixation process are discussed using well documented mathematical and physical formulae. The deeper understanding of these factors will enable pathologist to optimize the factors and use them in their favor.
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                Author and article information

                Contributors
                Journal
                Front Med (Lausanne)
                Front Med (Lausanne)
                Front. Med.
                Frontiers in Medicine
                Frontiers Media S.A.
                2296-858X
                20 February 2018
                2018
                : 5
                : 31
                Affiliations
                [1] 1Biomedical Engineering Graduate Program, University of Manitoba , Winnipeg, MB, Canada
                [2] 2Neuroscience Research Program, Kleysen Institute for Advanced Medicine, Winnipeg Health Sciences Centre , Winnipeg, MB, Canada
                [3] 3Department of Radiology, University of Manitoba , Winnipeg, MB, Canada
                [4] 4Division of Diagnostic Imaging, Winnipeg Health Sciences Centre , Winnipeg, MB, Canada
                [5] 5Department of Pathology, University of Manitoba , Winnipeg, MB, Canada
                [6] 6Department of Psychological and Brain Sciences, Johns Hopkins University , Baltimore, MD, United States
                Author notes

                Edited by: Juarez Antonio Simões Quaresma, Instituto Evandro Chagas, Brazil

                Reviewed by: Juergen Hench, University Hospital of Basel, Switzerland; Robert Turner, Max Planck Institute for Human Cognitive and Brain Sciences (MPG), Germany

                *Correspondence: Chase R. Figley, chase.figley@ 123456umanitoba.ca

                Specialty section: This article was submitted to Pathology, a section of the journal Frontiers in Medicine

                Article
                10.3389/fmed.2018.00031
                5826187
                29515998
                d0ba99c3-22a8-4407-a9d1-1daf76d82c9f
                Copyright © 2018 Shatil, Uddin, Matsuda and Figley.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 17 November 2017
                : 29 January 2018
                Page count
                Figures: 9, Tables: 3, Equations: 0, References: 59, Pages: 15, Words: 8753
                Categories
                Medicine
                Original Research

                ex vivo,fixation,formalin,longitudinal,postmortem,human brain,mri,myelin,diffusion,t1,t2

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