Osterode Wolf, Falkenberg Gerald, Regele Heinz
Universitätsklinik für Innere Medizin II, Medical University of Vienna, A-1090 Vienna, Austria.
Photon Science, Deutsches Elektronen-Synchrotron (DESY), D-22603 Hamburg, Germany.
J Imaging. 2022 Sep 21;8(10):254. doi: 10.3390/jimaging8100254.
This study aimed to investigate gadolinium (Gd) and bio-metals in a renal allograft of a patient who was shortly after transplantation repeatedly exposed to a Gd-based contrast agent (GBCA), with the purpose of determining whether Gd can be proven and spatially and quantitatively imaged. Further elemental associations between Gd and bio-metals were also investigated.
Archival paraffin-embedded kidney tissue (eight weeks after transplantation) was investigated by microscopic synchrotron X-ray fluorescence (µSRXRF) at the DORIS III storage ring, beamline L, at HASYLAB/DESY (Hamburg, Germany). For the quantification of elements, X-ray spectra were peak-fitted, and the net peak intensities were normalized to the intensity of the incoming monochromatic beam intensity. Concentrations were calculated by fundamental parameter-based program quant and external standardization.
Analysis of about 15,000 µSRXRF spectra (comprising allograft tissue of four cm) Gd distribution could be quantitatively demonstrated in a near histological resolution. Mean Gd resulted in 24 ± 55 ppm with a maximum of 2363 ppm. The standard deviation of ±55 ppm characterized the huge differences in Gd and not in detection accuracy. Gd was heterogeneously but not randomly distributed and was mostly found in areas with interstitial fibrosis and tubular atrophy. Concentrations of all other investigated elements in the allograft resembled those found in normal kidney tissue. No correlations between Gd and bio-metals such as calcium, strontium or zinc below ~40 ppm Gd existed. In areas with extremely high Gd, Gd was associated with iron and zinc.
We could show that no dose-dependent association between Gd and bio-metals exists-least in renal tissue-at Gd concentrations below ~40 ppm Gd. This was proven compared with a GBCA-exposed end-stage renal failure in which the mean Gd was ten-fold higher. Our results could shed additional light on Gd metabolism.
本研究旨在调查一名移植后不久反复接触钆基造影剂(GBCA)的患者肾移植中的钆(Gd)和生物金属,目的是确定是否能证实Gd并对其进行空间和定量成像。还研究了Gd与生物金属之间的进一步元素关联。
通过在德国汉堡HASYLAB/DESY的DORIS III储存环L光束线进行微观同步加速器X射线荧光(µSRXRF)分析存档的石蜡包埋肾组织(移植后8周)。为了对元素进行定量,对X射线光谱进行峰拟合,并将净峰强度归一化为入射单色光束强度。通过基于基本参数的程序quant和外标法计算浓度。
分析约15,000个µSRXRF光谱(包括4厘米的同种异体移植组织),可以在接近组织学分辨率下定量显示Gd分布。平均Gd含量为24±55 ppm,最高为2363 ppm。±55 ppm的标准偏差表征了Gd的巨大差异,而非检测准确性。Gd分布不均匀但并非随机分布,主要存在于间质纤维化和肾小管萎缩区域。同种异体移植中所有其他研究元素的浓度与正常肾组织中的浓度相似。在Gd浓度低于约40 ppm时,Gd与钙、锶或锌等生物金属之间不存在相关性。在Gd含量极高的区域,Gd与铁和锌有关。
我们可以证明,在Gd浓度低于约40 ppm时,Gd与生物金属之间不存在剂量依赖性关联——至少在肾组织中如此。与平均Gd含量高十倍的暴露于GBCA的终末期肾衰竭相比,这一点得到了证实。我们的结果可能会为Gd代谢提供更多线索。