Skip to main content
Erschienen in: Clinical Neuroradiology 4/2016

18.04.2015 | Original Article

Chronic T2 Lesions in Multiple Sclerosis are Heterogeneous Regarding Phase MR Imaging

verfasst von: S. Siemonsen, MD, K.L. Young, MD, M. Bester, MD, Dr. rer. nat. J. Sedlacik, C. Heesen, MD, J. Fiehler, MD, J.-P. Stellmann, MD

Erschienen in: Clinical Neuroradiology | Ausgabe 4/2016

Einloggen, um Zugang zu erhalten

Abstract

Purpose

Phase imaging provides additional information on multiple sclerosis (MS) lesions and may in combination with mean diffusivity (MD) and magnetization transfer ratio (MTR) help differentiating heterogeneity of MS lesion pathology.

Methods

Magnetic resonance imaging (MRI) was performed in 23 MS patients including diffusion tensor imaging (DTI), magnetization transfer imaging (MTI), and SWI. Mean values (MTR, MD, and homodyne filtered phase) from 138 chronic MS lesions and normal appearing white matter (NAWM) were obtained and correlations examined. For explorative analysis, a divisive hierarchical clustering algorithm was applied.

Results

Phase characteristics were an independent characteristic of chronic T2 lesions, as MTR and MD were not correlated with phase values (R = − 0.23, R = − 0.18). Dependent on MTR, MD, and phase, cluster analysis led to five lesion groups. Of the two groups with phase values close to NAWM, one presented with highest MD and most severe MTR decrease (p  =  0.01), the other with slight MD increase and MTR decrease. Two lesion groups with highest phase values (p  =  0.01) displayed slightly increased MD and moderate decrease in MTR. Clinical data including EDSS, disease duration, and age did not differ significantly between groups.

Conclusions

Increased phase is predominantly detectable in lesions with clear MTR decrease but only moderate MD increase. Phase images seem to represent an independent parameter for MS lesion characterization and may provide additional information on MS lesion heterogeneity.
Literatur
1.
Zurück zum Zitat Daumer M, Neuhaus A, Morrissey S, Hintzen R, Ebers GC. MRI as an outcome in multiple sclerosis clinical trials. Neurology. 2009;72(8):705–11. doi:10.1212/01.wnl.0000336916.38629.43.CrossRefPubMed Daumer M, Neuhaus A, Morrissey S, Hintzen R, Ebers GC. MRI as an outcome in multiple sclerosis clinical trials. Neurology. 2009;72(8):705–11. doi:10.1212/01.wnl.0000336916.38629.43.CrossRefPubMed
2.
Zurück zum Zitat Zivadinov R. Can imaging techniques measure neuroprotection and remyelination in multiple sclerosis? Neurology. 2007;68(22 Suppl 3):S72–82. doi:10.1212/01.wnl.0000275236.51129.d2.CrossRefPubMed Zivadinov R. Can imaging techniques measure neuroprotection and remyelination in multiple sclerosis? Neurology. 2007;68(22 Suppl 3):S72–82. doi:10.1212/01.wnl.0000275236.51129.d2.CrossRefPubMed
3.
Zurück zum Zitat Committee for Medicinal Products for Human Use (CHMP) Guideline on clinical investigation of medicinal products for the treatment of Multiple Sclerosis. European Medicines Agency. 2012; EMA/CHMP/771815/2011, Rev2. Committee for Medicinal Products for Human Use (CHMP) Guideline on clinical investigation of medicinal products for the treatment of Multiple Sclerosis. European Medicines Agency. 2012; EMA/CHMP/771815/2011, Rev2.
4.
Zurück zum Zitat Haacke EM, Cheng NY, House MJ, Liu Q, Neelavalli J, Ogg RJ, Khan A, Ayaz M, Kirsch W, Obenaus A. Imaging iron stores in the brain using magnetic resonance imaging. Magn Reson Imaging. 2005;23(1):1–25. doi:10.1016/j.mri.2004.10.001.CrossRefPubMed Haacke EM, Cheng NY, House MJ, Liu Q, Neelavalli J, Ogg RJ, Khan A, Ayaz M, Kirsch W, Obenaus A. Imaging iron stores in the brain using magnetic resonance imaging. Magn Reson Imaging. 2005;23(1):1–25. doi:10.1016/j.mri.2004.10.001.CrossRefPubMed
5.
Zurück zum Zitat Bagnato F, Hametner S, Yao B, van Gelderen P, Merkle H, Cantor FK, Lassmann H, Duyn JH. Tracking iron in multiple sclerosis: a combined imaging and histopathological study at 7 Tesla. Brain. 2011;134(Pt 12):3602–15. doi:10.1093/brain/awr278.CrossRefPubMed Bagnato F, Hametner S, Yao B, van Gelderen P, Merkle H, Cantor FK, Lassmann H, Duyn JH. Tracking iron in multiple sclerosis: a combined imaging and histopathological study at 7 Tesla. Brain. 2011;134(Pt 12):3602–15. doi:10.1093/brain/awr278.CrossRefPubMed
6.
Zurück zum Zitat Yao B, Li TQ, Gelderen P, Shmueli K, de Zwart JA, Duyn JH. Susceptibility contrast in high field MRI of human brain as a function of tissue iron content. Neuroimage. 2009;44(4):1259–66. doi:10.1016/j.neuroimage.2008.10.029.CrossRefPubMed Yao B, Li TQ, Gelderen P, Shmueli K, de Zwart JA, Duyn JH. Susceptibility contrast in high field MRI of human brain as a function of tissue iron content. Neuroimage. 2009;44(4):1259–66. doi:10.1016/j.neuroimage.2008.10.029.CrossRefPubMed
7.
Zurück zum Zitat He X, Yablonskiy DA. Biophysical mechanisms of phase contrast in gradient echo MRI. Proc Natl Acad Sci U S A. 2009;106(32):13558–63. doi:10.1073/pnas.0904899106.CrossRefPubMedPubMedCentral He X, Yablonskiy DA. Biophysical mechanisms of phase contrast in gradient echo MRI. Proc Natl Acad Sci U S A. 2009;106(32):13558–63. doi:10.1073/pnas.0904899106.CrossRefPubMedPubMedCentral
8.
Zurück zum Zitat Li TQ, Yao B, van Gelderen P, Merkle H, Dodd S, Talagala L, Koretsky AP, Duyn J. Characterization of T(2)* heterogeneity in human brain white matter. Magn Reson Med. 2009;62(6):1652–7. doi:10.1002/mrm.22156.CrossRefPubMedPubMedCentral Li TQ, Yao B, van Gelderen P, Merkle H, Dodd S, Talagala L, Koretsky AP, Duyn J. Characterization of T(2)* heterogeneity in human brain white matter. Magn Reson Med. 2009;62(6):1652–7. doi:10.1002/mrm.22156.CrossRefPubMedPubMedCentral
9.
Zurück zum Zitat Haacke EM, Makki M, Ge Y, Maheshwari M, Sehgal V, Hu J, Selvan M, Wu Z, Latif Z, Xuan Y, Khan O, Garbern J, Grossman RI. Characterizing iron deposition in multiple sclerosis lesions using susceptibility weighted imaging. J Magn Reson Imaging. 2009;29(3):537–44. doi:10.1002/jmri.21676.CrossRefPubMedPubMedCentral Haacke EM, Makki M, Ge Y, Maheshwari M, Sehgal V, Hu J, Selvan M, Wu Z, Latif Z, Xuan Y, Khan O, Garbern J, Grossman RI. Characterizing iron deposition in multiple sclerosis lesions using susceptibility weighted imaging. J Magn Reson Imaging. 2009;29(3):537–44. doi:10.1002/jmri.21676.CrossRefPubMedPubMedCentral
10.
Zurück zum Zitat Eissa A, Lebel RM, Korzan JR, Zavodni AE, Warren KG, Catz I, Emery DJ, Wilman AH. Detecting lesions in multiple sclerosis at 4.7 T using phase susceptibility-weighting and T2-weighting. J Magn Reson Imaging. 2009;30(4):737–42. doi:10.1002/jmri.21926.CrossRefPubMed Eissa A, Lebel RM, Korzan JR, Zavodni AE, Warren KG, Catz I, Emery DJ, Wilman AH. Detecting lesions in multiple sclerosis at 4.7 T using phase susceptibility-weighting and T2-weighting. J Magn Reson Imaging. 2009;30(4):737–42. doi:10.1002/jmri.21926.CrossRefPubMed
11.
Zurück zum Zitat Walsh AJ, Blevins G, Lebel RM, Seres P, Emery DJ, Wilman AH. Longitudinal MR imaging of iron in multiple sclerosis: an imaging marker of disease. Radiology. 2014;270(1):186–96. doi:10.1148/radiol.13130474.CrossRefPubMed Walsh AJ, Blevins G, Lebel RM, Seres P, Emery DJ, Wilman AH. Longitudinal MR imaging of iron in multiple sclerosis: an imaging marker of disease. Radiology. 2014;270(1):186–96. doi:10.1148/radiol.13130474.CrossRefPubMed
12.
Zurück zum Zitat Walsh AJ, Lebel RM, Eissa A, Blevins G, Catz I, Lu JQ, Resch L, Johnson ES, Emery DJ, Warren KG, Wilman AH. Multiple sclerosis: validation of MR imaging for quantification and detection of iron. Radiology. 2013;267(2):531–42. doi:10.1148/radiol.12120863.CrossRefPubMed Walsh AJ, Lebel RM, Eissa A, Blevins G, Catz I, Lu JQ, Resch L, Johnson ES, Emery DJ, Warren KG, Wilman AH. Multiple sclerosis: validation of MR imaging for quantification and detection of iron. Radiology. 2013;267(2):531–42. doi:10.1148/radiol.12120863.CrossRefPubMed
13.
Zurück zum Zitat Basser PJ, Pierpaoli C. Microstructural and physiological features of tissues elucidated by quantitative-diffusion-tensor MRI. J Magn Reson B. 1996;111(3):209–19.CrossRefPubMed Basser PJ, Pierpaoli C. Microstructural and physiological features of tissues elucidated by quantitative-diffusion-tensor MRI. J Magn Reson B. 1996;111(3):209–19.CrossRefPubMed
14.
Zurück zum Zitat Fox RJ. Picturing multiple sclerosis: conventional and diffusion tensor imaging. Semin Neurol. 2008;28(4):453–66. doi:10.1055/s-0028-1083689.CrossRefPubMed Fox RJ. Picturing multiple sclerosis: conventional and diffusion tensor imaging. Semin Neurol. 2008;28(4):453–66. doi:10.1055/s-0028-1083689.CrossRefPubMed
15.
Zurück zum Zitat Seewann A, Vrenken H, van der Valk P, Blezer EL, Knol DL, Castelijns JA, Polman CH, Pouwels PJ, Barkhof F, Geurts JJ. Diffusely abnormal white matter in chronic multiple sclerosis: imaging and histopathologic analysis. Arch Neurol. 2009;66(5):601–9. doi:10.1001/archneurol.2009.57.CrossRefPubMed Seewann A, Vrenken H, van der Valk P, Blezer EL, Knol DL, Castelijns JA, Polman CH, Pouwels PJ, Barkhof F, Geurts JJ. Diffusely abnormal white matter in chronic multiple sclerosis: imaging and histopathologic analysis. Arch Neurol. 2009;66(5):601–9. doi:10.1001/archneurol.2009.57.CrossRefPubMed
16.
Zurück zum Zitat Schmierer K, Scaravilli F, Altmann DR, Barker GJ, Miller DH. Magnetization transfer ratio and myelin in postmortem multiple sclerosis brain. Ann Neurol. 2004;56(3):407–15. doi:10.1002/ana.20202.CrossRefPubMed Schmierer K, Scaravilli F, Altmann DR, Barker GJ, Miller DH. Magnetization transfer ratio and myelin in postmortem multiple sclerosis brain. Ann Neurol. 2004;56(3):407–15. doi:10.1002/ana.20202.CrossRefPubMed
17.
Zurück zum Zitat Filippi M, Agosta F. Magnetization transfer MRI in multiple sclerosis. J Neuroimaging. 2007;17(Suppl 1):22S–6S. doi:10.1111/j.1552-6569.2007.00132.x.CrossRefPubMed Filippi M, Agosta F. Magnetization transfer MRI in multiple sclerosis. J Neuroimaging. 2007;17(Suppl 1):22S–6S. doi:10.1111/j.1552-6569.2007.00132.x.CrossRefPubMed
18.
Zurück zum Zitat Polman CH, Reingold SC, Banwell B, Clanet M, Cohen JA, Filippi M, Fujihara K, Havrdova E, Hutchinson M, Kappos L, Lublin FD, Montalban X, O'Connor P, Sandberg-Wollheim M, Thompson AJ, Waubant E, Weinshenker B, Wolinsky JS. Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol. 2011;69(2):292–302. doi:10.1002/ana.22366.CrossRefPubMedPubMedCentral Polman CH, Reingold SC, Banwell B, Clanet M, Cohen JA, Filippi M, Fujihara K, Havrdova E, Hutchinson M, Kappos L, Lublin FD, Montalban X, O'Connor P, Sandberg-Wollheim M, Thompson AJ, Waubant E, Weinshenker B, Wolinsky JS. Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol. 2011;69(2):292–302. doi:10.1002/ana.22366.CrossRefPubMedPubMedCentral
19.
Zurück zum Zitat van Waesberghe JH, Kamphorst W, De Groot CJ, van Walderveen MA, Castelijns JA, Ravid R, Lycklama à Nijeholt GJ, van der Valk P, Polman CH, Thompson AJ, Barkhof F. Axonal loss in multiple sclerosis lesions: magnetic resonance imaging insights into substrates of disability. Ann Neurol. 1999;46(5):747–54.CrossRefPubMed van Waesberghe JH, Kamphorst W, De Groot CJ, van Walderveen MA, Castelijns JA, Ravid R, Lycklama à Nijeholt GJ, van der Valk P, Polman CH, Thompson AJ, Barkhof F. Axonal loss in multiple sclerosis lesions: magnetic resonance imaging insights into substrates of disability. Ann Neurol. 1999;46(5):747–54.CrossRefPubMed
20.
Zurück zum Zitat Jenkinson M, Smith S. A global optimisation method for robust affine registration of brain images. Med Image Anal. 2001;5(2):143–56.CrossRefPubMed Jenkinson M, Smith S. A global optimisation method for robust affine registration of brain images. Med Image Anal. 2001;5(2):143–56.CrossRefPubMed
21.
Zurück zum Zitat Hammond KE, Metcalf M, Carvajal L, Okuda DT, Srinivasan R, Vigneron D, Nelson SJ, Pelletier D. Quantitative in vivo magnetic resonance imaging of multiple sclerosis at 7 Tesla with sensitivity to iron. Ann Neurol. 2008;64(6):707–13. doi:10.1002/ana.21582.CrossRefPubMed Hammond KE, Metcalf M, Carvajal L, Okuda DT, Srinivasan R, Vigneron D, Nelson SJ, Pelletier D. Quantitative in vivo magnetic resonance imaging of multiple sclerosis at 7 Tesla with sensitivity to iron. Ann Neurol. 2008;64(6):707–13. doi:10.1002/ana.21582.CrossRefPubMed
22.
Zurück zum Zitat Yao B, Bagnato F, Matsuura E, Merkle H, van Gelderen P, Cantor FK, Duyn JH. Chronic multiple sclerosis lesions: characterization with high-field-strength MR imaging. Radiology. 2012;262(1):206–15. doi:10.1148/radiol.11110601.CrossRefPubMedPubMedCentral Yao B, Bagnato F, Matsuura E, Merkle H, van Gelderen P, Cantor FK, Duyn JH. Chronic multiple sclerosis lesions: characterization with high-field-strength MR imaging. Radiology. 2012;262(1):206–15. doi:10.1148/radiol.11110601.CrossRefPubMedPubMedCentral
23.
Zurück zum Zitat Droogan AG, Clark CA, Werring DJ, Barker GJ, McDonald WI, Miller DH. Comparison of multiple sclerosis clinical subgroups using navigated spin echo diffusion-weighted imaging. Magn Reson Imaging. 1999;17(5):653–61. doi:S0730-725X(99)00011-9.CrossRefPubMed Droogan AG, Clark CA, Werring DJ, Barker GJ, McDonald WI, Miller DH. Comparison of multiple sclerosis clinical subgroups using navigated spin echo diffusion-weighted imaging. Magn Reson Imaging. 1999;17(5):653–61. doi:S0730-725X(99)00011-9.CrossRefPubMed
24.
Zurück zum Zitat Rovaris M, Gambini A, Gallo A, Falini A, Ghezzi A, Benedetti B, Sormani MP, Martinelli V, Comi G, Filippi M. Axonal injury in early multiple sclerosis is irreversible and independent of the short-term disease evolution. Neurology. 2005;65(10):1626–30. doi:10.1212/01.wnl.0000184493.06254.a6.CrossRefPubMed Rovaris M, Gambini A, Gallo A, Falini A, Ghezzi A, Benedetti B, Sormani MP, Martinelli V, Comi G, Filippi M. Axonal injury in early multiple sclerosis is irreversible and independent of the short-term disease evolution. Neurology. 2005;65(10):1626–30. doi:10.1212/01.wnl.0000184493.06254.a6.CrossRefPubMed
25.
Zurück zum Zitat Basser PJ. Inferring microstructural features and the physiological state of tissues from diffusion-weighted images. NMR Biomed. 1995;8(7–8):333–44.CrossRefPubMed Basser PJ. Inferring microstructural features and the physiological state of tissues from diffusion-weighted images. NMR Biomed. 1995;8(7–8):333–44.CrossRefPubMed
26.
Zurück zum Zitat De Groot CJ, Bergers E, Kamphorst W, Ravid R, Polman CH, Barkhof F, van der Valk P. Post-mortem MRI-guided sampling of multiple sclerosis brain lesions: increased yield of active demyelinating and (p)reactive lesions. Brain. 2001;124(Pt 8):1635–45.CrossRefPubMed De Groot CJ, Bergers E, Kamphorst W, Ravid R, Polman CH, Barkhof F, van der Valk P. Post-mortem MRI-guided sampling of multiple sclerosis brain lesions: increased yield of active demyelinating and (p)reactive lesions. Brain. 2001;124(Pt 8):1635–45.CrossRefPubMed
27.
Zurück zum Zitat Bitsch A, Kuhlmann T, Stadelmann C, Lassmann H, Lucchinetti C, Bruck W. A longitudinal MRI study of histopathologically defined hypointense multiple sclerosis lesions. Ann Neurol. 2001;49(6):793–6.CrossRefPubMed Bitsch A, Kuhlmann T, Stadelmann C, Lassmann H, Lucchinetti C, Bruck W. A longitudinal MRI study of histopathologically defined hypointense multiple sclerosis lesions. Ann Neurol. 2001;49(6):793–6.CrossRefPubMed
28.
Zurück zum Zitat Barkhof F, Bruck W, De Groot CJ, Bergers E, Hulshof S, Geurts J, Polman CH, van der Valk P. Remyelinated lesions in multiple sclerosis: magnetic resonance image appearance. Arch Neurol. 2003;60(8):1073–81. doi:10.1001/archneur.60.8.1073.CrossRefPubMed Barkhof F, Bruck W, De Groot CJ, Bergers E, Hulshof S, Geurts J, Polman CH, van der Valk P. Remyelinated lesions in multiple sclerosis: magnetic resonance image appearance. Arch Neurol. 2003;60(8):1073–81. doi:10.1001/archneur.60.8.1073.CrossRefPubMed
29.
Zurück zum Zitat Bruck W, Bitsch A, Kolenda H, Bruck Y, Stiefel M, Lassmann H. Inflammatory central nervous system demyelination: correlation of magnetic resonance imaging findings with lesion pathology. Ann Neurol. 1997;42(5):783–93. doi:10.1002/ana.410420515.CrossRefPubMed Bruck W, Bitsch A, Kolenda H, Bruck Y, Stiefel M, Lassmann H. Inflammatory central nervous system demyelination: correlation of magnetic resonance imaging findings with lesion pathology. Ann Neurol. 1997;42(5):783–93. doi:10.1002/ana.410420515.CrossRefPubMed
30.
Zurück zum Zitat Sahraian MA, Radue EW, Haller S, Kappos L. Black holes in multiple sclerosis: definition, evolution, and clinical correlations. Acta Neurol Scand. 2010;122(1):1–8. doi:10.1111/j.1600-0404.2009.01221.x.CrossRefPubMed Sahraian MA, Radue EW, Haller S, Kappos L. Black holes in multiple sclerosis: definition, evolution, and clinical correlations. Acta Neurol Scand. 2010;122(1):1–8. doi:10.1111/j.1600-0404.2009.01221.x.CrossRefPubMed
31.
Zurück zum Zitat van Walderveen MA, Kamphorst W, Scheltens P, van Waesberghe JH, Ravid R, Valk J, Polman CH, Barkhof F. Histopathologic correlate of hypointense lesions on T1-weighted spin-echo MRI in multiple sclerosis. Neurology. 1998;50(5):1282–8.CrossRefPubMed van Walderveen MA, Kamphorst W, Scheltens P, van Waesberghe JH, Ravid R, Valk J, Polman CH, Barkhof F. Histopathologic correlate of hypointense lesions on T1-weighted spin-echo MRI in multiple sclerosis. Neurology. 1998;50(5):1282–8.CrossRefPubMed
32.
Zurück zum Zitat Barkhof F, Karas GB, van Walderveen MA. T1 hypointensities and axonal loss. Neuroimaging Clin N Am. 2000;10(4):739–52.PubMed Barkhof F, Karas GB, van Walderveen MA. T1 hypointensities and axonal loss. Neuroimaging Clin N Am. 2000;10(4):739–52.PubMed
33.
Zurück zum Zitat Lassmann H. The pathologic substrate of magnetic resonance alterations in multiple sclerosis. Neuroimaging Clin N Am. 2008;18(4):563–76. doi:10.1016/j.nic.2008.06.005.CrossRefPubMed Lassmann H. The pathologic substrate of magnetic resonance alterations in multiple sclerosis. Neuroimaging Clin N Am. 2008;18(4):563–76. doi:10.1016/j.nic.2008.06.005.CrossRefPubMed
34.
Zurück zum Zitat Rovaris M, Gass A, Bammer R, Hickman SJ, Ciccarelli O, Miller DH, Filippi M. Diffusion MRI in multiple sclerosis. Neurology. 2005;65(10):1526–32. doi:10.1212/01.wnl.0000184471.83948.e0.CrossRefPubMed Rovaris M, Gass A, Bammer R, Hickman SJ, Ciccarelli O, Miller DH, Filippi M. Diffusion MRI in multiple sclerosis. Neurology. 2005;65(10):1526–32. doi:10.1212/01.wnl.0000184471.83948.e0.CrossRefPubMed
35.
Zurück zum Zitat Yablonskiy DA, Luo J, Sukstanskii AL, Iyer A, Cross AH. Biophysical mechanisms of MRI signal frequency contrast in multiple sclerosis. Proc Natl Acad Sci U S A. 2012;109(35):14212–7. doi:10.1073/pnas.1206037109.CrossRefPubMedPubMedCentral Yablonskiy DA, Luo J, Sukstanskii AL, Iyer A, Cross AH. Biophysical mechanisms of MRI signal frequency contrast in multiple sclerosis. Proc Natl Acad Sci U S A. 2012;109(35):14212–7. doi:10.1073/pnas.1206037109.CrossRefPubMedPubMedCentral
36.
Zurück zum Zitat Wiggermann V, Hernandez Torres E, Vavasour IM, Moore GR, Laule C, MacKay AL, Li DK, Traboulsee A, Rauscher A. Magnetic resonance frequency shifts during acute MS lesion formation. Neurology. 2013;81(3):211–8. doi:10.1212/WNL.0b013e31829bfd63.CrossRefPubMedPubMedCentral Wiggermann V, Hernandez Torres E, Vavasour IM, Moore GR, Laule C, MacKay AL, Li DK, Traboulsee A, Rauscher A. Magnetic resonance frequency shifts during acute MS lesion formation. Neurology. 2013;81(3):211–8. doi:10.1212/WNL.0b013e31829bfd63.CrossRefPubMedPubMedCentral
Metadaten
Titel
Chronic T2 Lesions in Multiple Sclerosis are Heterogeneous Regarding Phase MR Imaging
verfasst von
S. Siemonsen, MD
K.L. Young, MD
M. Bester, MD
Dr. rer. nat. J. Sedlacik
C. Heesen, MD
J. Fiehler, MD
J.-P. Stellmann, MD
Publikationsdatum
18.04.2015
Verlag
Springer Berlin Heidelberg
Erschienen in
Clinical Neuroradiology / Ausgabe 4/2016
Print ISSN: 1869-1439
Elektronische ISSN: 1869-1447
DOI
https://doi.org/10.1007/s00062-015-0389-8

Weitere Artikel der Ausgabe 4/2016

Clinical Neuroradiology 4/2016 Zur Ausgabe

Update Radiologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.