Quantitative magnetic resonance imaging indicates brain tissue alterations in patients after liver transplantation


Autoři: Lukas Laurids Goede aff001;  Henning Pflugrad aff001;  Birte Schmitz aff002;  Heinrich Lanfermann aff002;  Anita Blanka Tryc aff001;  Hannelore Barg-Hock aff004;  Jürgen Klempnauer aff004;  Karin Weissenborn aff001;  Xiao-Qi Ding aff002
Působiště autorů: Department of Neurology, Hannover Medical School, Hannover, Germany aff001;  Institute of Diagnostic and Interventional Neuroradiology, Hannover Medical School, Hannover, Germany aff002;  Integrated Research and Treatment Centre Transplantation (IFB-Tx), Hannover Medical School, Hannover, Germany aff003;  Clinic for Visceral and Transplant Surgery, Hannover Medical School, Hannover, Germany aff004
Vyšlo v časopise: PLoS ONE 14(9)
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pone.0222934

Souhrn

Purpose

To investigate cerebral microstructural alterations in patients treated with calcineurin inhibitors (CNI) after orthotopic liver transplantation (OLT) using quantitative magnetic resonance imaging (qMRI) and a cross-sectional study design.

Methods

Cerebral qMRI was performed in 85 patients in a median 10 years after OLT compared to 31 healthy controls. Patients were treated with different dosages of CNI or with a CNI-free immunosuppression (CNI-free: n = 19; CNI-low: n = 36; CNI-standard: n = 30). T2-, T2*- and T2’- relaxation times, as well as apparent diffusion coefficient (ADC) and fractional anisotropy (FA) were measured in brain gray and white matter by using the regions of interest method.

Results

In comparison to controls, patients revealed significantly increased T2, T2*, T2’, ADC and reduced FA, predominantly in the frontal white matter, indicating microstructural brain alterations represented by increased free water (increased T2), reduced neuronal metabolism (increased T2’) and a lower degree of spatial organization of the nervous fibers (reduced FA). CNI-low and CNI-free patients showed more alterations than CNI-standard patients. Analysis of their history revealed impairment of kidney function while under standard CNI dose suggesting that these patients may be more vulnerable to toxic CNI side-effects.

Conclusion

Our findings suggest that the individual sensitivity to toxic side effects should be considered when choosing an appropriate immunosuppressive regimen in patients after liver transplantation.

Klíčová slova:

Central nervous system – Diffusion tensor imaging – Immunosuppressives – Kidneys – Liver transplantation – Magnetic resonance imaging – Microstructure – Relaxation time


Zdroje

1. Herzer K, Strassburg CP, Braun F, Engelmann C, Guba M, Lehner F, et al. Selection and use of immunosuppressive therapies after liver transplantation: Current German practice. Clin Transplant. 2016;30: 487–501. doi: 10.1111/ctr.12708 26855333

2. Pillai AA, Levitsky J. Overview of immunosuppression in liver transplantation. World Journal of Gastroenterology. 2009. pp. 4225–4233. doi: 10.3748/wjg.15.4225 19750565

3. Åberg F, Isoniemi H, Höckerstedt K. Long-term results of liver transplantation. Scand J Surg. 2011;100: 14–21. doi: 10.1177/145749691110000104 21482501

4. Bernhardt M, Pflugrad H, Goldbecker A, Barg-Hock H, Knitsch W, Klempnauer J, et al. Central nervous system complications after liver transplantation: common but mostly transient phenomena. Liver Transpl. 2015;21: 224–232. doi: 10.1002/lt.24035 25369566

5. Lewis MB, Howdle PD. Neurologic complications of liver transplantation in adults. Neurology. 2003;61: 1174–8. doi: 10.1212/01.wnl.0000089487.42870.c6 14610116

6. Rompianesi G, Montalti R, Cautero N, De Ruvo N, Stafford A, Bronzoni C, et al. Neurological complications after liver transplantation as a consequence of immunosuppression: univariate and multivariate analysis of risk factors. Transpl Int. 2015;28: 864–9. doi: 10.1111/tri.12564 25790037

7. Mueller AR, Platz K-P, Bechstein W-O, Schattenfroh N, Stoltenburg-Didinger G, Blumhardt G, et al. Neurotoxicity after orthotopic liver transplantation: A comparison between cyclosporine and fk506. Transplantation. 1994;58: 155–170. 7518974

8. García Martínez R, Rovira A, Alonso J, Aymerich FX, Huerga E, Jacas C, et al. A long-term study of changes in the volume of brain ventricles and white matter lesions after successful liver transplantation. Transplantation. 2010;89: 589–594. doi: 10.1097/TP.0b013e3181ca7bb3 20118844

9. Ding XQ, Wittkugel O, Goebell E, Förster AF, Grzyska U, Zeumer H, et al. Clinical applications of quantitative T2 determination: A complementary MRI tool for routine diagnosis of suspected myelination disorders. Eur J Paediatr Neurol. 2008;12: 298–308. doi: 10.1016/j.ejpn.2007.08.012 17964834

10. Ding XQ, Sun Y, Kruse B, Illies T, Zeumer H, Fiehler J, et al. Microstructural callosal abnormalities in normal-appearing brain of children with developmental delay detected with diffusion tensor imaging. Eur Radiol. 2009;19: 1537–1543. doi: 10.1007/s00330-009-1296-7 19184035

11. Ding XQ, Fiehler J, Kohlschütter B, Wittkugel O, Grzyska U, Zeumer H, et al. MRI abnormalities in normal-appearing brain tissue of treated adult PKU patients. J Magn Reson Imaging. 2008;27: 998–1004. doi: 10.1002/jmri.21289 18425822

12. Leppert IR, Almli CR, McKinstry RC, Mulkern R V., Pierpaoli C, Rivkin MJ, et al. T2 relaxometry of normal pediatric brain development. J Magn Reson Imaging. 2009;29: 258–267. doi: 10.1002/jmri.21646 19161173

13. Weissenborn K, Bültmann E, Donnerstag F, Giesemann AM, Götz F, Worthmann H, et al. Quantitative MRI shows cerebral microstructural damage in hemolytic-uremic syndrome patients with severe neurological symptoms but no changes in conventional MRI. Neuroradiology. 2013;55: 819–825. doi: 10.1007/s00234-013-1176-3 23559401

14. Herynek V, Wagnerová D, Hejlová I, Dezortová M, Hájek M. Changes in the brain during long-term follow-up after liver transplantation. J Magn Reson Imaging. 2012;35: 1332–7. doi: 10.1002/jmri.23599 22315008

15. Pflugrad H, Schrader A-K, Tryc AB, Ding X-Q, Lanfermann H, Jäckel E, et al. Longterm calcineurin inhibitor therapy and brain function in patients after liver transplantation. Liver Transplant. 2018;24: 56–66. doi: 10.1002/lt.24984 29156491

16. Randolph C, Tierney MC, Mohr E, Chase TN. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS): Preliminary Clinical Validity. J Clin Exp Neuropsychol (Neuropsychology, Dev Cogn Sect A). 1998;20: 310–319. doi: 10.1076/jcen.20.3.310.823 9845158

17. Goldbecker A, Weissenborn K, Shahrezaei GH, Afshar K, Rümke S, Barg-Hock H, et al. Comparison of the most favoured methods for the diagnosis of hepatic encephalopathy in liver transplantation candidates. Gut. 2013;62: 1497–1504. doi: 10.1136/gutjnl-2012-303262 23297006

18. Mooney S, Hasssanein TI, Hilsabeck RC, Ziegler EA, Carlson M, Maron LM, et al. Utility of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) in patients with end-stage liver disease awaiting liver transplant. Arch Clin Neuropsychol. 2007;22: 175–186. doi: 10.1016/j.acn.2006.12.005 17280813

19. Eylers V V, Maudsley AA, Bronzlik P, Dellani PR, Lanfermann H, Ding XQ. Detection of normal aging effects on human brain metabolite concentrations and microstructure with whole-brain MR spectroscopic imaging and quantitative MR imaging. AJNR Am J Neuroradiol. 2016;37: 447–454. doi: 10.3174/ajnr.A4557 26564440

20. Abràmoff MD, Magalhães PJ, Ram SJ. Image processing with imageJ. Biophotonics International. 2004. pp. 36–41. doi: 10.1117/1.3589100 21721809

21. Howell DC. Statistical Methods for Psychology. 8th ed. The Statistician. Belmont: Wadsworth Publishing Co Inc; 2011. doi: 10.2307/2348956

22. Ding X-Q, Kucinski T, Wittkugel O, Goebell E, Grzyska U, Görg M, et al. Normal brain maturation characterized with age-related T2 relaxation times: an attempt to develop a quantitative imaging measure for clinical use. Invest Radiol. 2004;39: 740–746. doi: 10.1097/00004424-200412000-00005 15550835

23. Holland BA, Haas DK, Norman D, Brant-Zawadzki M, Newton TH. MRI of normal brain maturation. AJNR Am J Neuroradiol. 1986;7: 201–208. 3082150

24. Dawe RJ, Bennett DA, Schneider JA, Leurgans SE, Kotrotsou A, Boyle PA, et al. Ex vivo T2 relaxation: Associations with age-related neuropathology and cognition. Neurobiol Aging. 2014;35: 1549–1561. doi: 10.1016/j.neurobiolaging.2014.01.144 24582637

25. Wagner M, Jurcoane A, Volz S, Magerkurth J, Zanella FE, Neumann-Haefelin T, et al. Age-related changes of cerebral autoregulation: New insights with quantitative T2′-mapping and pulsed arterial spin-labeling MR imaging. AJNR Am J Neuroradiol. 2012;33: 2081–2087. doi: 10.3174/ajnr.A3138 22700750

26. Wagner M, Magerkurth J, Volz S, Jurcoane A, Singer OC, Neumann-Haefelin T, et al. T2’- and PASL-based perfusion mapping at 3 Tesla: Influence of oxygen-ventilation on cerebral autoregulation. J Magn Reson Imaging. 2012;36: 1347–1352. doi: 10.1002/jmri.23777 22911952

27. Holst B, Siemonsen S, Finsterbusch J, Bester M, Schippling S, Martin R, et al. T2’ imaging indicates decreased tissue metabolism in frontal white matter of MS patients. Mult Scler. 2009;15: 701–7. doi: 10.1177/1352458509103713 19482862

28. Blinkenberg M, Jensen C V, Holm S, Paulson OB, Sørensen PS. A longitudinal study of cerebral glucose metabolism, MRI, and disability in patients with MS. Neurology. 1999;53: 149–153. doi: 10.1212/wnl.53.1.149 10408551

29. Bammer R. Basic principles of diffusion-weighted imaging. Eur J Radiol. 2003;45: 169–184. S0720048X02003030 [pii] doi: 10.1016/s0720-048x(02)00303-0 12595101

30. Lyng H, Haraldseth O, Rofstad EK. Measurement of cell density and necrotic fraction in human melanoma xenografts by diffusion weighted magnetic resonance imaging. Magn Reson Med. 2000;43: 828–836. doi: 10.1002/1522-2594(200006)43:6<828::aid-mrm8>3.0.co;2-p 10861877

31. Loubinoux I, Volk A, Borredon J, Guirimand S, Tiffon B, Seylaz J, et al. Spreading of vasogenic edema and cytotoxic edema assessed by quantitative diffusion and T2 magnetic resonance imaging. Stroke. 1997;28: 419–426. doi: 10.1161/01.str.28.2.419 9040700

32. Dogan F, Dokumaci D Sen, Yildirim A, Bozdogan E, Boyaci FN, Koca B, et al. Brain diffusion changes in Eisenmenger syndrome. Br J Radiol. 2016;89: 20151007. doi: 10.1259/bjr.20151007 27767324

33. Filippi M, Cercignani M, Inglese M, Horsfield MA, Comi G. Diffusion tensor magnetic resonance imaging in multiple sclerosis. Neurology. 2001;56: 304–311. doi: 10.1212/wnl.56.3.304 11171893


Článek vyšel v časopise

PLOS One


2019 Číslo 9
Nejčtenější tento týden