Department of Psychiatric Research, Diakonhjemmet Hospital, Oslo 0319, Norway; NORMENT, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Department of Psychiatric Research, Diakonhjemmet Hospital, Oslo 0319, Norway; NORMENT, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Neuroimage. 2021 Dec 15;245:118709. doi: 10.1016/j.neuroimage.2021.118709. Epub 2021 Nov 27.
The ratio of T1-weighted (T1w) and T2-weighted (T2w) magnetic resonance imaging (MRI) images is often used as a proxy measure of cortical myelin. However, the T1w/T2w-ratio is based on signal intensities that are inherently non-quantitative and known to be affected by extrinsic factors. To account for this a variety of processing methods have been proposed, but a systematic evaluation of their efficacy is lacking. Given the dependence of the T1w/T2w-ratio on scanner hardware and T1w and T2w protocols, it is important to ensure that processing pipelines perform well also across different sites.
We assessed a variety of processing methods for computing cortical T1w/T2w-ratio maps, including correction methods for nonlinear field inhomogeneities, local outliers, and partial volume effects as well as intensity normalisation. These were implemented in 33 processing pipelines which were applied to four test-retest datasets, with a total of 170 pairs of T1w and T2w images acquired on four different MRI scanners. We assessed processing pipelines across datasets in terms of their reproducibility of expected regional distributions of cortical myelin, lateral intensity biases, and test-retest reliability regionally and across the cortex. Regional distributions were compared both qualitatively with histology and quantitatively with two reference datasets, YA-BC and YA-B1+, from the Human Connectome Project.
Reproducibility of raw T1w/T2w-ratio distributions was overall high with the exception of one dataset. For this dataset, Spearman rank correlations increased from 0.27 to 0.70 after N3 bias correction relative to the YA-BC reference and from -0.04 to 0.66 after N4ITK bias correction relative to the YA-B1+ reference. Partial volume and outlier corrections had only marginal effects on the reproducibility of T1w/T2w-ratio maps and test-retest reliability. Before intensity normalisation, we found large coefficients of variation (CVs) and low intraclass correlation coefficients (ICCs), with total whole-cortex CV of 10.13% and whole-cortex ICC of 0.58 for the raw T1w/T2w-ratio. Intensity normalisation with WhiteStripe, RAVEL, and Z-Score improved total whole-cortex CVs to 5.91%, 5.68%, and 5.19% respectively, whereas Z-Score and Least Squares improved whole-cortex ICCs to 0.96 and 0.97 respectively.
In the presence of large intensity nonuniformities, bias field correction is necessary to achieve acceptable correspondence with known distributions of cortical myelin, but it can be detrimental in datasets with less intensity inhomogeneity. Intensity normalisation can improve test-retest reliability and inter-subject comparability. However, both bias field correction and intensity normalisation methods vary greatly in their efficacy and may affect the interpretation of results. The choice of T1w/T2w-ratio processing method must therefore be informed by both scanner and acquisition protocol as well as the given study objective. Our results highlight limitations of the T1w/T2w-ratio, but also suggest concrete ways to enhance its usefulness in future studies.
T1 加权（T1w）和 T2 加权（T2w）磁共振成像（MRI）图像的比值常被用作皮质髓鞘的替代指标。然而，T1w/T2w 比值基于固有非定量的信号强度，且已知受外在因素的影响。为了解决这个问题，已经提出了各种处理方法，但缺乏对其效果的系统评估。鉴于 T1w/T2w 比值依赖于扫描仪硬件以及 T1w 和 T2w 协议，确保处理管道在不同站点也能良好运行非常重要。
我们评估了用于计算皮质 T1w/T2w 比值图的各种处理方法，包括用于非线性磁场不均匀性、局部异常值和部分容积效应的校正方法以及强度归一化。这些方法在 33 个处理管道中实现，并应用于四个测试-再测试数据集，总共在四台不同的 MRI 扫描仪上采集了 170 对 T1w 和 T2w 图像。我们根据皮质髓鞘的预期区域分布、横向强度偏差以及区域和整个皮质的测试-再测试可靠性，评估处理管道在数据集之间的可重复性。区域分布既与组织学进行了定性比较，也与人类连接组计划（Human Connectome Project）中的 YA-BC 和 YA-B1+ 两个参考数据集进行了定量比较。
除了一个数据集之外，原始 T1w/T2w 比值分布的重现性总体较高。对于该数据集，与 YA-BC 参考相比，经过 N3 偏置校正后，Spearman 秩相关系数从 0.27 增加到 0.70，与 YA-B1+ 参考相比，经过 N4ITK 偏置校正后，Spearman 秩相关系数从-0.04 增加到 0.66。部分容积和异常值校正对 T1w/T2w 比值图的重现性和测试-再测试可靠性只有微小影响。在进行强度归一化之前，我们发现变异系数（CV）较大且组内相关系数（ICC）较低，原始 T1w/T2w 比值的全皮质总 CV 为 10.13%，全皮质 ICC 为 0.58。使用 WhiteStripe、RAVEL 和 Z-Score 进行强度归一化后，全皮质总 CV 分别提高到 5.91%、5.68%和 5.19%，而 Z-Score 和最小二乘法则分别将全皮质 ICC 提高到 0.96 和 0.97。
在存在大的强度非均匀性的情况下，为了与已知的皮质髓鞘分布达到可接受的对应关系，需要进行偏置场校正，但在强度不均匀性较小的数据集上，偏置场校正可能会产生不利影响。强度归一化可以提高测试-再测试的可靠性和受试者间的可比性。然而，偏置场校正和强度归一化方法在效果上差异很大，可能会影响结果的解释。因此，T1w/T2w 比值处理方法的选择必须同时考虑扫描仪和采集协议以及给定的研究目标。我们的结果突出了 T1w/T2w 比值的局限性，但也为提高其在未来研究中的实用性提供了具体途径。
