Diagnostic accuracy of susceptibility-weighted magnetic resonance imaging for the evaluation of pineal gland calcification

Lisa C Adams, Sarah M Böker, Yvonne Y Bender, Gerd Diederichs, Eva M Fallenberg, Moritz Wagner, Bernd Hamm, Marcus R Makowski, Lisa C Adams, Sarah M Böker, Yvonne Y Bender, Gerd Diederichs, Eva M Fallenberg, Moritz Wagner, Bernd Hamm, Marcus R Makowski

Abstract

Objectives: To determine the diagnostic performance of susceptibility-weighted magnetic resonance imaging (SWMR) for the detection of pineal gland calcifications (PGC) compared to conventional magnetic resonance imaging (MRI) sequences, using computed tomography (CT) as a reference standard.

Methods: 384 patients who received a 1.5 Tesla MRI scan including SWMR sequences and a CT scan of the brain between January 2014 and October 2016 were retrospectively evaluated. 346 patients were included in the analysis, of which 214 showed PGC on CT scans. To assess correlation between imaging modalities, the maximum calcification diameter was used. Sensitivity and specificity and intra- and interobserver reliability were calculated for SWMR and conventional MRI sequences.

Results: SWMR reached a sensitivity of 95% (95% CI: 91%-97%) and a specificity of 96% (95% CI: 91%-99%) for the detection of PGC, whereas conventional MRI achieved a sensitivity of 43% (95% CI: 36%-50%) and a specificity of 96% (95% CI: 91%-99%). Detection rates for calcifications in SWMR and conventional MRI differed significantly (95% versus 43%, p<0.001). Diameter measurements between SWMR and CT showed a close correlation (R2 = 0.85, p<0.001) with a slight but not significant overestimation of size (SWMR: 6.5 mm ± 2.5; CT: 5.9 mm ± 2.4, p = 0.02). Interobserver-agreement for diameter measurements was excellent on SWMR (ICC = 0.984, p < 0.0001).

Conclusions: Combining SWMR magnitude and phase information enables the accurate detection of PGC and offers a better diagnostic performance than conventional MRI with CT as a reference standard.

Conflict of interest statement

Competing Interests: MRM has received grants from the Deutsche Forschungsgesellschaft (DFG) and GIF (German Israel Research Foundation). BH has received research grants for the Department of Radiology, Charité – Universitätsmedizin Berlin from the following companies: 1. Abbott, 2. Actelion Pharmaceuticals, 3. Bayer Schering Pharma, 4. Bayer Vital, 5. BRACCO Group, 6. Bristol-Myers Squibb, 7. Charite research organisation GmbH, 8. Deutsche Krebshilfe, 9. Dt. Stiftung für Herzforschung, 10. Essex Pharma, 11. EU Programmes, 12. Fibrex Medical Inc., 13. Focused Ultrasound Surgery Foundation, 14. Fraunhofer Gesellschaft, 15. Guerbet, 16. INC Research, 17. lnSightec Ud., 18. IPSEN Pharma, 19. Kendlel MorphoSys AG, 20. Lilly GmbH, 21. Lundbeck GmbH, 22. MeVis Medical Solutions AG, 23. Nexus Oncology, 24. Novartis, 25. Parexel Clinical Research Organisation Service, 26. Perceptive, 27. Pfizer GmbH, 28. Philipps, 29. Sanofis-Aventis S.A, 30. Siemens, 31. Spectranetics GmbH, 32. Terumo Medical Corporation, 33. TNS Healthcare GMbH, 34. Toshiba, 35. UCB Pharma, 36. Wyeth Pharma, 37. Zukunftsfond Berlin (TSB), 38. Amgen, 39. AO Foundation, 40. BARD, 41. BBraun, 42. Boehring Ingelheimer, 43. Brainsgate, 44. PPD (Clinical Research Organisation), 45. CELLACT Pharma, 46. Celgene, 47. CeloNova BioSciences, 48. Covance, 49. DC Deviees, Ine. USA, 50. Ganymed, 51. Gilead Sciences, 52. Glaxo Smith Kline, 53. ICON (Clinical Research Organisation), 54. Jansen, 55. LUX Bioseienees, 56. MedPass, 57. Merek, 58. Mologen, 59. Nuvisan, 60. Pluristem, 61. Quintiles, 62. Roehe, 63. Sehumaeher GmbH (Sponsoring eines Workshops), 64. Seattle Geneties, 65. Symphogen, 66. TauRx Therapeuties Ud., 67. Accovion, 68. AIO: Arbeitsgemeinschaft Internistische Onkologie, 69. ASR Advanced sleep research, 70. Astellas, 71. Theradex, 72. Galena Biopharma, 73. Chiltern, 74. PRAint, 75. lnspiremd, 76. Medronic, 77. Respicardia, 78. Silena Therapeutics, 79. Spectrum Pharmaceuticals, 80. St. Jude., 81. TEVA, 82. Theorem, 83. Abbvie, 84. Aesculap, 85. Biotronik, 86. Inventivhealth, 87. ISA Therapeutics, 88. LYSARC, 89. MSD, 90. novocure, 91. Ockham oncology, 92. Premier-research, 93. Psi-cro, 94. Tetec-ag, 94. Tetec-ag, 95. Winicker-norimed, 96. Achaogen Inc, 97. ADIR, 98. AstraZenaca AB, 99. Demira Inc, 100.Euroscreen S.A., 101. Galmed Research and Development Ltd., 102. GETNE, 103. Guidant Europe NV, 104. Holaira Inc., 105. Immunomedics Inc., 106. Innate Pharma, 107. Isis Pharmaceuticals Inc, 108. Kantar Health GmbH, 109. MedImmune Inc, 110. Medpace Germany GmbH (CRO), 111. Merrimack Pharmaceuticals Inc, 112. Millenium Pharmaceuticals Inc, 113. Orion Corporation Orion Pharma, 114. Pharmacyclics Inc, 115. PIQUR Therapeutics Ltd, 116. Pulmonx International Sárl, 117. Servier (CRO), 118. SGS Life Science Services (CRO), 119. Treshold Pharmaceuticals Inc. The remaining authors have no conflicts of interest and did not receive any funds. There are no patents, products in development or marketed products to declare. This does not alter the authors' adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1. Imaging findings of a 63-year-old…
Fig 1. Imaging findings of a 63-year-old man with a calcified pineal gland.
(A), CT shows a sharply defined oval-shaped pineal calcification with a diameter of 7 mm. In axial T1-weighted MRI (B) and in axial T2-weighted MRI (C) it is hardly possible to demarcate the calcified area against the surrounding tissue. In conventional MRI, it is not possible to reliably identify the hypointense foci as calcifications. The inverted SWMR magnitude image (D) and the phase image (E) show well-defined focal hyperintensities in the pineal region area. While the image information solely derived from the magnitude image is not superior to conventional MRI sequences, the combination of SWMR magnitude and phase image allows for a clear and reliable identification of diamagnetic calcifications. Magnified images are provided for (B), (C), (D) and (E). As CT and MRI of the brain have diverged reference lines with the bicommissural line used as a convenience standard for MRI and the orbitomeatal line used for CT, the slice angles vary slightly.
Fig 2. Imaging findings of a 55-year-old…
Fig 2. Imaging findings of a 55-year-old woman with a calcified pineal gland.
(A), CT shows a sharply defined oval-shaped pineal calcification with a diameter of 11 mm. In axial T1-weighted MRI (B) and in axial T2-weighted MRI (C) it is hardly possible to demarcate the calcified area against the surrounding tissue. In conventional MRI, it is not possible to reliably identify the hypointense foci as calcifications. The inverted SWMR magnitude image (D) and the phase image (E) show well-defined focal hyperintensities in the pineal region area. While the image information solely derived from the magnitude image is not superior to conventional MRI sequences, the combination of SWMR magnitude and phase image allows for a clear and reliable identification of diamagnetic calcifications. Magnified images are provided for (B), (C), (D) and (E). As CT and MRI of the brain have diverged reference lines with the bicommissural line used as a convenience standard for MRI and the orbitomeatal line used for CT, the slice angles vary accordingly.
Fig 3
Fig 3
Bland–Altman plots for the assessment of intraobserver variability for diameter measurements of calcifications in meningiomas in conventional MRI (A) and SWMR (B). The mean ratio was 1.00 for conventional MRI (CI: 0.79 to 1.22) and 1.01 for SWMR magnitude images (CI: 0.82 to 1.19). The mean ratio of the data is illustrated by the central horizontal line. Upper and lower reference lines show the upper and lower limits of agreement (95% confidence intervals).
Fig 4. Linear regression and Bland–Altman plot…
Fig 4. Linear regression and Bland–Altman plot for the assessment of interobserver variability for diameter measurements of calcifications in meningiomas in SWMR.
Diameter measurements show an excellent correlation (R2 = 0.91) with a mean ratio of 1.00 (CI: 0.72 to 1.29) between calcification measurements of the two readers in SWMR magnitude images. The mean ratio of diameter measurements of readers 1 and 2 is illustrated by the central horizontal line. Upper and lower reference lines show the upper and lower limits of agreement (95% confidence intervals).
Fig 5
Fig 5
Linear regression and Bland-Altman plot of the difference between diameter measurements of calcifications in CT and SWMR (A) and of the difference between diameter measurements of calcifications in CT and MRI T1 and T2 weighted images (B). Diameter measurements show a strong correlation (R2 = 0.85) between SWMR magnitude images and the reference standard CT with a mean difference of 1.13 (CI: 0.73 to 1.53). In comparison, correlation between MRI T1 and T2 weighted images and CT is only moderate (R2 = 0.49) with a mean difference of 0.92 (CI: 0.53 to 1.30). The mean difference of the data is illustrated by the central horizontal line. Upper and lower reference lines show the upper and lower limits of agreement (95% confidence intervals).

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