Cited by 27Advanced Neuroimaging Techniques and ApplicationsAdvanced MRI Techniques and ApplicationsNMR spectroscopy and applications

Viable and fixed white matter: diffusion magnetic resonance comparisons and contrasts at physiological temperature

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Richardson, Simon, Siow, Bernard, Panagiotaki, Eleftheria, Schneider, Torben, Lythgoe, Mark F., Alexander, Daniel C.·2014·Magnetic Resonance in Medicine

Abstract

PURPOSE: Fixed samples have been used extensively in diffusion MRI (dMRI) studies. However, fixation causes significant structural changes in tissue. The purpose of this study was to evaluate fixed white matter as a surrogate for viable white matter during development and validation of dMRI methods. METHODS: dMRI data was acquired from fixed and viable rat optic nerves maintained in identical conditions in a viable isolated tissue (VIT) chamber. The chamber preserves tissue integrity for 10 h at 37°C. Diffusion tensors (DT) and multi-compartment white matter signal models were fitted to the data. RESULTS: When comparing VIT and fixed tissue, DT parameters demonstrated that fixation causes significant reductions in axial diffusivity and increases in radial diffusivity. However, both tissues exhibited similar responses to changes in diffusion times and gradient strengths. Multicompartment models demonstrated differences in parameter estimates (e.g., directional diffusivities) that were analogous to differences in DT parameters. Similarities in multi-compartment model rankings suggested that tissue water populations were broadly maintained postfixation. CONCLUSIONS: The data demonstrate that fixed tissue, while maintaining the broad water environment of viable tissue, differs significantly in diffusion parameters. Results from dMRI experiments on fixed tissue may correlate with-but will not directly translate into-results from viable tissue.

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  • While temperature and fixation affect diffusivity values, and ADC in fixed tissue is significantly lower than in vivo, anisotropy values are comparable between in vivo and ex vivo samples.

    “While temperature and fixation affect diffusivity values, and ADC in fixed tissue is significantly lower than in vivo (Richardson et al., 2014), anisotropy values are comparable between in vivo and ex vivo samples (Sun et al., 2001, 2003; Zhang et al., 2012).”

    From The role of myelination in measures of white matter integrity: Combination of diffusion tensor imaging and two-photon microscopy of CLARITY intact brains (2017) · cites this paper as Richardson et al., 2014

    The Introduction states that temperature differences greatly affect measured diffusion coefficients, and DTI (Experiment A) reports lower axial diffusivity in fixed than viable isolated tissue. But the study compares fixed tissue with viable isolated tissue, not directly with in vivo samples, and the cited passages do not establish a significantly lower overall ADC. The anisotropy clause is attributed to other sources and is not part of this verdict. (LLM, conf=0.84)

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Research works printed but not linked: 55

  1. Ferguson B, Matyszak MK, Esiri MM, Perry VH. Axonal damage in acute multiple sclerosis lesions. Brain 1997;120:393-399.
  2. Kidwell CS, Alger JR, Di Salle F, Starkman S, Villablanca P, Bentson J, Saver JL. Diffusion MRI in patients with transient ischemic attacks. Stroke 1999;30:1174-1180.
  3. Schaefer PW, Grant PE, Gonzalez RG. Diffusion-weighted MR imaging of the brain. Radiology 2000;217:331-345.
  4. Le Bihan D. Looking into the functional architecture of the brain with diffusion MRI. Nat Rev Neurosci 2003;4:469-480.
  5. Basser PJ, Mattiello J, LeBihan D. MR diffusion tensor spectroscopy and imaging. Biophys J 1994;66:259-267.
  6. Alexander DC, Hubbard PL, Hall MG, Moore EA, Ptito M, Parker GJM, Dyrby TB. Orientationally invariant indices of axon diameter and density from diffusion MRI. NeuroImage 2010;52:1374-1389.
  7. Assaf Y, Blumenfeld-Katzir T, Yovel Y, Basser PJ. Axcaliber: a method for measuring axon diameter distribution from diffusion MRI. Magn Reson Med 2008;59:1347-1354.
  8. Stanisz GJ, Wright GA, Henkelman RM, Szafer A. An analytical model of restricted diffusion in bovine optic nerve. Magn Reson Med 1997;37:103-111.
  9. Behrens TEJ, Woolrich MW, Jenkinson M, Johansen-Berg H, Nunes RG, Clare S, Matthews PM, Brady JM, Smith SM. Characterization and propagation of uncertainty in diffusion-weighted MR imaging. Magn Reson Med 2003;50:1077-1088.
  10. Assaf Y, Basser PJ. Composite hindered and restricted model of diffu- sion (CHARMED) MR imaging of the human brain. NeuroImage 2005; 27:48-58.
  11. Alexander DC. A general framework for experiment design in diffu- sion MRI and its application in measuring direct tissue- microstructure features. Magn Reson Med 2008;60:439-448.
  12. Panagiotaki E, Schneider T, Siow B, Hall MG, Lythgoe MF, Alexander DC. Compartment models of the diffusion MR signal in brain white matter: a taxonomy and comparison. NeuroImage 2012; 59:2241-2254.
  13. Lasic ˇS, Nilsson M, L€ att J, Sta ˚hlberg F, Topgaard D. Apparent exchange rate mapping with diffusion MRI. Magn Reson Med 2011; 66:356-365.
  14. Zhou F-L, Hubbard PL, Eichhorn SJ, Parker GJM. Coaxially electro- spun axon-mimicking fibers for diffusion magnetic resonance imag- ing. ACS Appl Mater Inter 2012;4:6311-6316.
  15. Komlosh ME, € Ozarslan E, Lizak MJ, Horkay F, Schram V, Shemesh N, Cohen Y, Basser PJ. Pore diameter mapping using double pulsed- field gradient MRI and its validation using a novel glass capillary array phantom. J Magn Reson 2011;208:128-135.
  16. Siow B, Drobnjak I, Chatterjee A, Lythgoe MF, Alexander DC. Estima- tion of pore size in a microstructure phantom using the optimised gradient waveform diffusion weighted NMR sequence. J Magn Reson 2012;214:51-60.
  17. Ford JC, Hackney DB, Alsop DC, Jara H, Joseph PM, Hand CM, Black P. MRI characterization of diffusion coefficients in a rat spinal cord injury model. Magn Reson Med 1994;31:488-494.
  18. Holmes AA, Scollan DF, Winslow RL. Direct histological validation of diffusion tensor MRI in formaldehyde-fixed myocardium. Magn Reson Med 2000;44:157-161.
  19. Leergaard TB, White NS, de Crespigny A, Bolstad I, D'Arceuil H, Bjaalie JG, Dale AM. Quantitative histological validation of diffusion MRI fiber orientation distributions in the rat brain. PLoS One 2010;5: e8595.
  20. Dyrby TB, Sïgaard LV, Hall MG, Ptito M, Alexander DC. Contrast and stability of the axon diameter index from microstructure imaging with diffusion MRI. Magn Reson Med 2013;70:711-721.
  21. Le Bihan D, Poupon C, Amadon A, Lethimonnier F. Artifacts and pit- falls in diffusion MRI. J Magn Reson Imaging 2006;24:478-488.
  22. Fox CH, Johnson FB, Whiting J, Roller PP. Formaldehyde fixation. J Histochem Cytochem 1985;33:845-853.
  23. Richardson S, Siow B, Batchelor AM, Lythgoe MF, Alexander DC. A viable isolated tissue system: a tool for detailed MR measurements and controlled perturbation in physiologically stable tissue. Magn Reson Med 2013;69:1603-1610.
  24. Anderson AW, Zhong J, Petroff OA, Szafer A, Ransom BR, Prichard JW, Gore JC. Effects of osmotically driven cell volume changes on diffusion-weighted imaging of the rat optic nerve. Magn Reson Med 1996;35:162-167.
  25. Blackband SJ, Bui JD, Buckley DL, Zelles T, Plant HD, Inglis BA, Phillips MI. MR microscopy of perfused brain slices. Magn Reson Med 1997;38:1012-1015.
  26. Madi S, Hasan KM, Narayana PA. Diffusion tensor imaging of in vivo and excised rat spinal cord at 7 T with an icosahedral encoding scheme. Magn Reson Med 2005;53:118-125.
  27. Thelwall PE, Shepherd TM, Stanisz GJ, Blackband SJ. Effects of tem- perature and aldehyde fixation on tissue water diffusion properties, studied in an erythrocyte ghost tissue model. Magn Reson Med 2006; 56:282-289.
  28. Reese BE. The distribution of axons according to diameter in the optic nerve and optic tract of the rat. Neuroscience 1987;22:1015- 1024.
  29. Cook P, Bai Y, Gilani N, Seunarine K, Hall M, Parker G, Alexander D. Camino: Open-source diffusion-MRI reconstruction and process- ing. In Proceedings of the 14th Annual Meeting of ISMRM. Seattle, Washington, USA, 2006. p. 2759.
  30. Jones DK, Basser PJ. "Squashing peanuts and smashing pumpkins": how noise distorts diffusion-weighted MR data. Magn Reson Med 2004;52:979-993.
  31. Alexander DC, Barker GJ. Optimal imaging parameters for fiber- orientation estimation in diffusion MRI. NeuroImage 2005;27:357-367.
  32. The probable error of a mean. Biometrika 1908;6:1-25.
  33. Marquardt DW. An algorithm for least-squares estimation of nonlin- ear parameters. Journal of the Society for Industrial & Applied Mathe- matics 1963;11:431-441.
  34. Alexander DC. Modelling, fitting and sampling in diffusion MRI. In: Laidlaw D, Weickert J, editors. Visualization and processing of tensor fields. Berlin, Heidelberg: Springer Berlin Heidelberg; 2009. p. 3-20.
  35. Schwarz G. Estimating the dimension of a model. The Annals of Sta- tistics 1978;6:461-464.
  36. Clark CA, Le Bihan D. Water diffusion compartmentation and anisot- ropy at high b values in the human brain. Magn Reson Med 2000;44: 852-859.
  37. Hui ES, Cheung MM, Chan KC, Wu EX. B-value dependence of DTI quantitation and sensitivity in detecting neural tissue changes. Neu- roImage 2010;49:2366.
  38. Le Bihan D, Turner R, Douek P. Is water diffusion restricted in human brain white matter? An echo-planar NMR imaging study. Neu- roreport 1993;4:887-890.
  39. Clark CA, Hedehus M, Moseley ME. Diffusion time dependence of the apparent diffusion tensor in healthy human brain and white mat- ter disease. Magn Reson Med 2001;45:1126-1129.
  40. Holz M, Heil SR, Sacco A. Temperature-dependent self-diffusion coefficients of water and six selected molecular liquids for calibration in accurate 1H NMR PFG measurements. Phys Chem Chem Phys 2000;2:4740-4742.
  41. Garthwaite G, Goodwin DA, Batchelor AM, Leeming K, Garthwaite J. Nitric oxide toxicity in CNS white matter: an in vitro study using rat optic nerve. Neuroscience 2002;109:145-155.
  42. Einstein A. € Uber die von der molekularkinetischen Theorie der W€ arme geforderte Bewegung von in ruhenden Fl€ ussigkeiten suspen- dierten Teilchen. Ann Phys 1905;322:549-560.
  43. Barazany D, Basser PJ, Assaf Y. In vivo measurement of axon diame- ter distribution in the corpus callosum of rat brain. Brain 2009;132: 1210-1220.
  44. Schachter M, Does M, Anderson A, Gore J. Measurements of restricted diffusion using an oscillating gradient spin-echo sequence. J Magn Reson 2000;147:232-237.
  45. Merboldt K-D, H€ anicke W, Frahm J. Diffusion imaging using stimu- lated echoes. Magn Reson Med 1991;19:233-239.
  46. Farrell JAD, Landman BA, Jones CK, Smith SA, Prince JL, van Zijl PCM, Mori S. Effects of signal-to-noise ratio on the accuracy and reproducibility of diffusion tensor imaging-derived fractional anisot- ropy, mean diffusivity, and principal eigenvector measurements at 1.5T. J. Magn Reson Imaging 2007;26:756-767.
  47. Stanisz GJ, Henkelman RM. Diffusional anisotropy of T2 components in bovine optic nerve. Magn Reson Med 1998;40:405-410.
  48. Dula AN, Gochberg DF, Valentine HL, Valentine WM, Does MD. Mul- tiexponential T2, magnetization transfer, and quantitative histology in white matter tracts of rat spinal cord. Magn Reson Med 2010;63: 902-909.
  49. Emeis D, Anker W, Wittern K-P. Quantitative 13C NMR spectroscopic studies on the equilibrium of formaldehyde with its releasing cos- metic preservatives. Anal Chem 2007;79:2096-2100.
  50. Jones D. Reactions of aldehydes with unsaturated fatty acids during histological fixation. Histochem J 1972;4:421-465.
  51. Alberts B, Johnson A, Lewis J, et al. Membrane transport of small molecules and the electrical properties of membranes. In: Molecular biology of the cell. 4th edition. New York: Garland Science; 2002: 615-658.
  52. Van Harreveld A, Khattab FI. Chloride movements during perfusion fixation with glutaraldehyde. Anat Rec 1968;162:467-477.
  53. Heyderman E. Histotechnology. A self-instructional text. Histopathol- ogy 1992;20:91-91.
  54. Hildebrand C, Hahn R. Relation between myelin sheath thickness and axon size in spinal cord white matter of some vertebrate species. J Neurol Sci 1978;38:421-434.
  55. Paus T, Collins D, Evans A, Leonard G, Pike B, Zijdenbos A. Matura- tion of white matter in the human brain: a review of magnetic reso- nance studies. Brain Res Bull 2001;54:255-266.

Cited by

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Authors
Richardson, S., Siow, B., Panagiotaki, E., Schneider, T., Lythgoe, M. F., & Alexander, D. C.
Affiliations
  • University College London (GB)
  • UCL Queen Square Institute of Neurology (GB)
Corresponding author
Richardson, Simon
Venue
Magnetic Resonance in Medicine
Publisher
Wiley
Published
2013-11-14
Volume
72
Issue
4
Pages
1151-1161
ISSN
  • 0740-3194 (ISSN-L)
  • 1522-2594
OpenAlex
W1920754069
Cited by
27
References
4
Citations by year
2026: 2 · 2025: 1 · 2024: 2 · 2022: 1 · 2020: 5 · 2019: 4 · 2018: 3 · 2017: 3 · 2016: 2 · 2015: 2 · 2014: 1 · 2013: 1
FWCI
1.55
Type
journal article
Language
en
Open access
Locations
  • Magnetic Resonance in Medicine (publishedVersion)
  • PubMed (publishedVersion)
  • UCL Discovery (University College London) (submittedVersion)
Funders
Engineering and Physical Sciences Research Council (EP/G007748/1, EP/H046410/1)
Topics
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced Neuroimaging Techniques and Applications
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced MRI Techniques and Applications
  • Physical Sciences › Physics and Astronomy › Nuclear and High Energy Physics › NMR spectroscopy and applications
Keywords
tissue fixation, white matter, diffusion MRI, optic nerve, axial diffusivity, radial diffusivity, diffusion tensor, rats, physiological temperature
MeSH terms
Animals, Male, Optic Nerve, Sensitivity and Specificity, Specimen Handling, Reproducibility of Results, Artifacts, Tissue Embedding, Rats, Sprague-Dawley, Models, Animal, Rats, Diffusion Tensor Imaging, White Matter, In Vitro Techniques

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