Birkl Christoph, Panzer Marlene, Kames Christian, Birkl-Toeglhofer Anna Maria, Rauscher Alexander, Glodny Bernhard, Gizewski Elke R, Zoller Heinz
Department of Radiology, Medical University of Innsbruck, Innsbruck, Austria.
Neuroimaging Research Core Facility, Medical University of Innsbruck, Innsbruck, Austria.
Eur Radiol Exp. 2025 Aug 23;9(1):80. doi: 10.1186/s41747-025-00622-w.
R2* and quantitative susceptibility mapping (QSM) are regarded as robust techniques for assessing iron content in the brain. While these techniques are established for normal or moderate iron levels, their usability in extreme iron overload, as seen in aceruloplasminemia (ACP), is unclear. We aimed to evaluate various R2* and QSM algorithms in assessing brain iron levels in patients with ACP compared to healthy controls.
We acquired a three-dimensional multiecho gradient-echo sequence for R2* and QSM in three patients with ACP and three healthy subjects. Six algorithms each for R2* and QSM were compared. QSM was performed with referencing to whole brain, to cerebrospinal fluid and without referencing. R2* and QSM values were assessed in the caudate nucleus, putamen, globus pallidus, and thalamus.
R2* values varied significantly across algorithms, particularly in the putamen (F(5,50) = 16.51, p < 0.001). For QSM, reference region choice (F(5,150) = 264, p < 0.001) and algorithm selection (F(2,9) = 10, p < 0.001) had an impact on susceptibility values. In patients, referencing to whole brain yielded lower susceptibility values than cerebrospinal fluid (median = 0.147 ppm, range = 0.527 ppm versus median = 0.279 ppm, range = 0.593 ppm).
Extreme iron overload amplifies variability in R2* and QSM measurements. QSM referencing is particularly challenging in diffuse whole-brain iron accumulation; thus, analysis with multiple reference regions might mitigate bias. Both algorithm selection and referencing approaches play a pivotal role in determining measurement accuracy and clinical interpretation under extreme brain iron overload.
As QSM transitions into clinical use, it will encounter cases of extreme iron overload. Our study in patients with aceruloplasminemia revealed that the choice of reference region significantly influences susceptibility values, with variations exceeding algorithm-dependent differences.
R2* and QSM vary across algorithms in brain tissue with iron overload. Whole-brain referenced QSM leads to lower susceptibility values in aceruloplasminemia patients. QSM, if properly processed, provides reliable maps in iron overload brain regions. In brain regions with extremely high iron content, R2* mapping might fail.
R2和定量磁化率成像（QSM）被视为评估脑内铁含量的可靠技术。虽然这些技术已用于正常或中等铁水平的评估，但其在如无铜蓝蛋白血症（ACP）所见的极端铁过载情况下的可用性尚不清楚。我们旨在评估各种R2和QSM算法在评估ACP患者与健康对照者脑铁水平方面的情况。
我们为3例ACP患者和3名健康受试者采集了用于R2和QSM的三维多回波梯度回波序列。比较了R2和QSM各自的6种算法。QSM分别参照全脑、脑脊液进行，以及不进行参照。在尾状核、壳核、苍白球和丘脑评估R2*和QSM值。
R2*值在各算法间差异显著，尤其是在壳核（F(5,50) = 16.51，p < 0.001）。对于QSM，参照区域的选择（F(5,150) = 264，p < 0.001）和算法选择（F(2,9) = 10，p < 0.001）对磁化率值有影响。在患者中，参照全脑得到的磁化率值低于参照脑脊液（中位数 = 0.147 ppm，范围 = 0.527 ppm 对比中位数 = 0.279 ppm，范围 = 0.593 ppm）。
极端铁过载会放大R2*和QSM测量的变异性。在弥漫性全脑铁沉积中，QSM参照尤其具有挑战性；因此，使用多个参照区域进行分析可能会减轻偏差。在极端脑铁过载情况下，算法选择和参照方法在确定测量准确性和临床解读方面都起着关键作用。
随着QSM过渡到临床应用，将会遇到极端铁过载的病例。我们对无铜蓝蛋白血症患者的研究表明，参照区域的选择显著影响磁化率值，其变化超过算法相关的差异。
在铁过载的脑组织中，R2和QSM因算法而异。在无铜蓝蛋白血症患者中，参照全脑的QSM导致较低的磁化率值。如果处理得当，QSM可在铁过载脑区提供可靠的图谱。在铁含量极高的脑区，R2成像可能会失败。
