Solaiyappan Meiyappan, Bharti Santosh Kumar, Sharma Raj Kumar, Dbouk Mohamad, Nizam Wasay, Brock Malcolm V, Goggins Michael G, Bhujwalla Zaver M
Department of Radiology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Commun Med (Lond). 2025 Jan 21;5(1):24. doi: 10.1038/s43856-024-00727-0.
Routine screening to detect silent but deadly cancers such as pancreatic ductal adenocarcinoma (PDAC) can significantly improve survival, creating an important need for a convenient screening test. High-resolution proton (1H) magnetic resonance spectroscopy (MRS) of plasma identifies circulating metabolites that can allow detection of cancers such as PDAC that have highly dysregulated metabolism.
We first acquired 1H MR spectra of human plasma samples classified as normal, benign pancreatic disease and malignant (PDAC). We next trained a system of artificial neural networks (ANNs) to process and discriminate these three classes using the full spectrum range and resolution of the acquired spectral data. We then identified and ranked spectral regions that played a salient role in the discrimination to provide interpretability of the results. We tested the accuracy of the ANN performance using blinded plasma samples.
We show that our ANN approach yields, in a cross validation-based training of 170 samples, a sensitivity and a specificity of 100% for malignant versus non-malignant (normal and disease combined) discrimination. The trained ANNs achieve a sensitivity and specificity of 87.5% and 93.1% respectively (AUC: ROC = 0.931, P-R = 0.854), with 45 blinded plasma samples. Further, we show that the salient spectral regions of the ANN discrimination correspond to metabolites of known importance for their role in cancers.
Our results demonstrate that the ANN approach presented here can identify PDAC from 1H MR plasma spectra to provide a convenient plasma-based assay for population-level screening of PDAC. The ANN approach can be suitably expanded to detect other cancers with metabolic dysregulation.
常规筛查以检测诸如胰腺导管腺癌(PDAC)等隐匿但致命的癌症可显著提高生存率,因此迫切需要一种便捷的筛查测试。血浆的高分辨率质子(1H)磁共振波谱(MRS)可识别循环代谢物,从而能够检测出代谢高度失调的癌症,如PDAC。
我们首先获取了分类为正常、良性胰腺疾病和恶性(PDAC)的人体血浆样本的1H MR波谱。接下来,我们训练了一个人工神经网络(ANN)系统,以使用所采集光谱数据的全谱范围和分辨率来处理和区分这三类样本。然后,我们识别并排列了在区分过程中起显著作用的光谱区域,以提供结果的可解释性。我们使用盲法血浆样本测试了ANN性能的准确性。
我们表明,在基于170个样本的交叉验证训练中,我们的ANN方法对恶性与非恶性(正常和疾病合并)的区分具有100%的敏感性和特异性。对于45个盲法血浆样本,训练后的ANN分别实现了87.5%的敏感性和93.1%的特异性(AUC:ROC = 0.931,P-R = 0.854)。此外,我们表明ANN区分的显著光谱区域对应于因其在癌症中的作用而已知具有重要意义的代谢物。
我们的结果表明,本文提出的ANN方法可从1H MR血浆波谱中识别出PDAC,从而为基于血浆的PDAC人群水平筛查提供一种便捷的检测方法。ANN方法可适当地扩展以检测其他代谢失调的癌症。