Characterizing Protein Concentration in Cerebrospinal Fluid with T2 Component Analysis.

Tatsuya Koizumi, Seiko Shimizu, Chihiro Akiba, Hidenori Kakizoe, Hideki Bandai, Kenichi Sato, Hidekazu Nagasawa, Ikuko Ogino, Madoka Nakajima, Shinya Yamada, Koichi Oshio, Masakazu Miyajima
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Abstract

Purpose: T2 values are hypothesized to be reduced where protein accumulates in the cerebrospinal fluid (CSF). We aimed to verify the accuracy of Carr-Purcell-Meiboom-Gil (CPMG) pulses and non-negative least squares (NNLS) analysis in visualizing protein concentrations by mapping the T2 values.

Methods: We first dissolved 1.2g of bovine serum albumin powder in 4 mL of artificial CSF to purify an albumin solution with a concentration of 4.5 mM. Artificial CSF was added thereto, and eight types of albumin solutions, with concentrations of 0.002-4.5 mM, were purified. We acquired this albumin solution with CPMG pulses and NNLS, decomposed the T2 values per pixel, and derived 25 T2 component values of 60-2000 ms. We assessed the change of T2 values by the difference in albumin concentration of a single voxel. Finally, we used the method to assess T2 values from two patients, one with a subdural hematoma and one with a suprasellar cystic tumor. T2 component values were plotted graphically, presented individually, and created in color maps.

Results: T2 component values for albumin concentrations ranging from 0.056 to 4.55 mM showed different T2 peaks, whereas, for concentrations 0.002 to 0.019 mM, the peaks were similar heights and overlapped. Peak width was similar for all concentrations. The color maps successfully reflected the changes in T2 values across both RGB color patterns. T2 components for albumin samples with 2.5 mM and 6.1 mM concentrations within a single voxel were represented separately and reflected the ratio of the two samples in nine different regions of interest within one slice. In the clinical cases, the T2 component map imaged differences in albumin concentrations, similar to those observed in the albumin samples.

Conclusion: The present method with CPMG sequences and NNLS provide adequate images to differentiate accumulating protein concentrations in the CSF, even at the level of a single pixel.

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用 T2 成分分析法表征脑脊液中的蛋白质浓度
目的:据推测,蛋白质在脑脊液(CSF)中聚集时,T2 值会降低。我们旨在通过绘制 T2 值,验证卡尔-普塞尔-梅布姆-吉尔(CPMG)脉冲和非负最小二乘法(NNLS)分析在显示蛋白质浓度方面的准确性:我们首先将 1.2 克牛血清白蛋白粉末溶解在 4 毫升人工 CSF 中,提纯出浓度为 4.5 毫摩尔的白蛋白溶液。将人工 CSF 加入其中,纯化出浓度为 0.002-4.5 mM 的八种白蛋白溶液。我们用 CPMG 脉冲和 NNLS 采集了白蛋白溶液,分解了每个像素的 T2 值,得出了 60-2000 ms 的 25 个 T2 分量值。我们通过单个体素的白蛋白浓度差异来评估 T2 值的变化。最后,我们使用该方法评估了两名患者的 T2 值,其中一名患者患有硬膜下血肿,另一名患者患有鞍上囊性肿瘤。T2 分量值以图表形式绘制,单独显示,并绘制成彩色地图:白蛋白浓度在 0.056 至 4.55 mM 之间的 T2 分量值显示出不同的 T2 峰,而浓度在 0.002 至 0.019 mM 之间的 T2 峰高度相似且重叠。所有浓度的峰宽相似。彩色图谱成功地反映了两种 RGB 颜色模式中 T2 值的变化。单个体素内 2.5 毫摩尔和 6.1 毫摩尔浓度的白蛋白样本的 T2 分量被分别表示出来,反映了一个切片内九个不同感兴趣区中两种样本的比率。在临床病例中,T2分量图成像的白蛋白浓度差异与白蛋白样本中观察到的差异相似:本方法采用 CPMG 序列和 NNLS,可提供足够的图像来区分 CSF 中累积的蛋白质浓度,即使在单个像素的水平上也是如此。
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