MR imaging for the quantitative assessment of brain iron in aceruloplasminemia: A postmortem validation study
Lena H.P. Vroegindeweij,
Piotr A. Wielopolski,
Agnita J.W. Boon,
J.H. Paul Wilson,
Rob M. Verdijk,
Sipeng Zheng,
Sylvestre Bonnet,
Lucia Bossoni,
Louise van der Weerd,
Juan A. Hernandez-Tamames,
Janneke G. Langendonk
Affiliations
Lena H.P. Vroegindeweij
Department of Internal Medicine, Center for Lysosomal and Metabolic Diseases, Porphyria Center Rotterdam, Erasmus University Medical Center, Erasmus MC, Rotterdam, the Netherlands
Piotr A. Wielopolski
Department of Radiology and Nuclear Medicine, Erasmus University Medical Center, Erasmus MC, Rotterdam, the Netherlands
Agnita J.W. Boon
Department of Neurology, Erasmus University Medical Center, Erasmus MC, Rotterdam, the Netherlands
J.H. Paul Wilson
Department of Internal Medicine, Center for Lysosomal and Metabolic Diseases, Porphyria Center Rotterdam, Erasmus University Medical Center, Erasmus MC, Rotterdam, the Netherlands
Rob M. Verdijk
Department of Pathology, Erasmus University Medical Center, Erasmus MC, Rotterdam, the Netherlands
Sipeng Zheng
Leiden Institute of Chemistry, Leiden University, Leiden, the Netherlands
Sylvestre Bonnet
Leiden Institute of Chemistry, Leiden University, Leiden, the Netherlands
Lucia Bossoni
C.J. Gorter Center for High field MRI, Department of Radiology, Leiden University Medical Center, Leiden, the Netherlands
Louise van der Weerd
C.J. Gorter Center for High field MRI, Department of Radiology, Leiden University Medical Center, Leiden, the Netherlands; Department of Human Genetics, Leiden University Medical Center, Leiden, the Netherlands
Juan A. Hernandez-Tamames
Department of Radiology and Nuclear Medicine, Erasmus University Medical Center, Erasmus MC, Rotterdam, the Netherlands
Janneke G. Langendonk
Department of Internal Medicine, Center for Lysosomal and Metabolic Diseases, Porphyria Center Rotterdam, Erasmus University Medical Center, Erasmus MC, Rotterdam, the Netherlands; Corresponding author.
Aims: Non-invasive measures of brain iron content would be of great benefit in neurodegeneration with brain iron accumulation (NBIA) to serve as a biomarker for disease progression and evaluation of iron chelation therapy. Although magnetic resonance imaging (MRI) provides several quantitative measures of brain iron content, none of these have been validated for patients with a severely increased cerebral iron burden. We aimed to validate R2* as a quantitative measure of brain iron content in aceruloplasminemia, the most severely iron-loaded NBIA phenotype. Methods: Tissue samples from 50 gray- and white matter regions of a postmortem aceruloplasminemia brain and control subject were scanned at 1.5 T to obtain R2*, and biochemically analyzed with inductively coupled plasma mass spectrometry. For gray matter samples of the aceruloplasminemia brain, sample R2* values were compared with postmortem in situ MRI data that had been obtained from the same subject at 3 T – in situ R2*. Relationships between R2* and tissue iron concentration were determined by linear regression analyses. Results: Median iron concentrations throughout the whole aceruloplasminemia brain were 10 to 15 times higher than in the control subject, and R2* was linearly associated with iron concentration. For gray matter samples of the aceruloplasminemia subject with an iron concentration up to 1000 mg/kg, 91% of variation in R2* could be explained by iron, and in situ R2* at 3 T and sample R2* at 1.5 T were highly correlated. For white matter regions of the aceruloplasminemia brain, 85% of variation in R2* could be explained by iron. Conclusions: R2* is highly sensitive to variations in iron concentration in the severely iron-loaded brain, and might be used as a non-invasive measure of brain iron content in aceruloplasminemia and potentially other NBIA disorders.
