Abstract：
OBJECTIVE: 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.
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.
摘要：
目的：脑铁含量的非侵入性措施将对具有脑铁积累（NBIA）的神经变性具有很大的益处，可作为疾病进展和铁螯合治疗评估的生物标志物。尽管磁共振成像（MRI）提供了几种定量测量脑铁含量的方法，对于脑铁负荷严重增加的患者，这些方法均未得到验证。我们的目的是验证R2*作为一个定量的测量脑铁含量在阿瑟纤虫血症，最严重的铁负载NBIA表型。
方法：在1.5T扫描来自50个死后肢端纤毛虫血症脑和对照组的灰质和白质区域的组织样本，以获得R2*，用电感耦合等离子体质谱法进行生化分析。对于Acerulofilememia脑的灰质样本，将样本R2*值与在3T-原位R2*时从同一受试者获得的死后原位MRI数据进行比较。通过线性回归分析确定R2*与组织铁浓度之间的关系。
结果：整个Acerulofilememia脑中的铁浓度中位数比对照组高10至15倍，R2*与铁浓度呈线性关系。对于铁浓度高达1000mg/kg的Acerulofilememia受试者的灰质样品，91%的R2*变化可以用铁解释，3T的原位R2*和1.5T的样品R2*高度相关。对于Acerulofilememia脑的白质区域，R2*中85%的变化可由铁解释。
结论：R2*对严重铁负荷的大脑中铁浓度的变化高度敏感，并且可能被用作一种非侵入性的测量肢端纤溶蛋白血症和潜在的其他NBIA疾病的脑铁含量。
方法：在1.5T扫描来自50个死后肢端纤毛虫血症脑和对照组的灰质和白质区域的组织样本，以获得R2*，用电感耦合等离子体质谱法进行生化分析。对于Acerulofilememia脑的灰质样本，将样本R2*值与在3T-原位R2*时从同一受试者获得的死后原位MRI数据进行比较。通过线性回归分析确定R2*与组织铁浓度之间的关系。
结果：整个Acerulofilememia脑中的铁浓度中位数比对照组高10至15倍，R2*与铁浓度呈线性关系。对于铁浓度高达1000mg/kg的Acerulofilememia受试者的灰质样品，91%的R2*变化可以用铁解释，3T的原位R2*和1.5T的样品R2*高度相关。对于Acerulofilememia脑的白质区域，R2*中85%的变化可由铁解释。
结论：R2*对严重铁负荷的大脑中铁浓度的变化高度敏感，并且可能被用作一种非侵入性的测量肢端纤溶蛋白血症和潜在的其他NBIA疾病的脑铁含量。
