Lucas Alfredo, Vadali Chetan, Mouchtaris Sofia, Arnold T Campbell, Gugger James J, Kulick-Soper Catherine, Josyula Mariam, Petillo Nina, Das Sandhitsu, Dubroff Jacob, Detre John A, Stein Joel M, Davis Kathryn A
Perelman School of Medicine, University of Pennsylvania.
Department of Bioengineering, University of Pennsylvania.
medRxiv. 2024 May 30:2024.05.28.24308027. doi: 10.1101/2024.05.28.24308027.
Positron Emission Tomography (PET) using fluorodeoxyglucose (FDG-PET) is a standard imaging modality for detecting areas of hypometabolism associated with the seizure onset zone (SOZ) in temporal lobe epilepsy (TLE). However, FDG-PET is costly and involves the use of a radioactive tracer. Arterial Spin Labeling (ASL) offers an MRI-based quantification of cerebral blood flow (CBF) that could also help localize the SOZ, but its performance in doing so, relative to FDG-PET, is limited. In this study, we seek to improve ASL's diagnostic performance by developing a deep learning framework for synthesizing FDG-PET-like images from ASL and structural MRI inputs.
We included 68 epilepsy patients, out of which 36 had well lateralized TLE. We compared the coupling between FDG-PET and ASL CBF values in different brain regions, as well as the asymmetry of these values across the brain. We additionally assessed each modality's ability to lateralize the SOZ across brain regions. Using our paired PET-ASL data, we developed FlowGAN, a generative adversarial neural network (GAN) that synthesizes PET-like images from ASL and T1-weighted MRI inputs. We tested our synthetic PET images against the actual PET images of subjects to assess their ability to reproduce clinically meaningful hypometabolism and asymmetries in TLE.
We found variable coupling between PET and ASL CBF values across brain regions. PET and ASL had high coupling in neocortical temporal and frontal brain regions (Spearman's > 0.30, p < 0.05) but low coupling in mesial temporal structures (Spearman's < 0.30, p > 0.05). Both whole brain PET and ASL CBF asymmetry values provided good separability between left and right TLE subjects, but PET (AUC = 0.96, 95% CI: [0.88, 1.00]) outperformed ASL (AUC = 0.81; 95% CI: [0.65, 0.96]). FlowGAN-generated images demonstrated high structural similarity to actual PET images (SSIM = 0.85). Globally, asymmetry values were better correlated between synthetic PET and original PET than between ASL CBF and original PET, with a mean correlation increase of 0.15 (95% CI: [0.07, 0.24], <0.001, Cohen's = 0.91). Furthermore, regions that had poor ASL-PET correlation (e.g. mesial temporal structures) showed the greatest improvement with synthetic PET images.
FlowGAN improves ASL's diagnostic performance, generating synthetic PET images that closely mimic actual FDG-PET in depicting hypometabolism associated with TLE. This approach could improve non-invasive SOZ localization, offering a promising tool for epilepsy presurgical assessment. It potentially broadens the applicability of ASL in clinical practice and could reduce reliance on FDG-PET for epilepsy and other neurological disorders.
使用氟脱氧葡萄糖的正电子发射断层扫描(FDG - PET)是检测颞叶癫痫(TLE)中与癫痫发作起始区(SOZ)相关的低代谢区域的标准成像方式。然而,FDG - PET成本高昂且涉及使用放射性示踪剂。动脉自旋标记(ASL)提供了一种基于磁共振成像(MRI)的脑血流量(CBF)定量方法,这也有助于定位SOZ,但相对于FDG - PET,其在这方面的表现有限。在本研究中,我们试图通过开发一个深度学习框架来提高ASL的诊断性能,该框架可从ASL和结构MRI输入合成类似FDG - PET的图像。
我们纳入了68例癫痫患者,其中36例患有明确单侧化的TLE。我们比较了不同脑区中FDG - PET与ASL CBF值之间的耦合,以及这些值在全脑的不对称性。我们还评估了每种成像方式在不同脑区定位SOZ的能力。利用我们配对的PET - ASL数据,我们开发了FlowGAN,这是一种生成对抗神经网络(GAN),可从ASL和T1加权MRI输入合成类似PET的图像。我们将合成的PET图像与受试者的实际PET图像进行测试,以评估其再现TLE中具有临床意义的低代谢和不对称性的能力。
我们发现全脑不同区域PET与ASL CBF值之间的耦合存在差异。PET与ASL在新皮质颞叶和额叶脑区具有高度耦合(斯皮尔曼相关系数>0.30,p<0.05),但在内侧颞叶结构中耦合度较低(斯皮尔曼相关系数<0.30,p>0.05)。全脑PET和ASL CBF不对称值在左侧和右侧TLE受试者之间都提供了良好的区分度,但PET(曲线下面积[AUC]=0.96,95%置信区间:[0.88,1.00])的表现优于ASL(AUC = 0.81;95%置信区间:[0.65,0.96])。FlowGAN生成的图像与实际PET图像显示出高度的结构相似性(结构相似性指数[SSIM]=0.85)。总体而言,合成PET与原始PET之间的不对称值相关性优于ASL CBF与原始PET之间的相关性,平均相关性增加0.15(95%置信区间:[0.07,0.24],p<0.001,科恩效应量=0.91)。此外,ASL - PET相关性较差的区域(如内侧颞叶结构)在合成PET图像中显示出最大的改善。
FlowGAN提高了ASL的诊断性能,生成的合成PET图像在描绘与TLE相关的低代谢方面与实际FDG - PET非常相似。这种方法可以改善非侵入性SOZ定位,为癫痫术前评估提供一种有前景的工具。它可能会扩大ASL在临床实践中的适用性,并减少癫痫和其他神经系统疾病对FDG - PET的依赖。