Zong Weiwei, Lee Joon K, Liu Chang, Carver Eric N, Feldman Aharon M, Janic Branislava, Elshaikh Mohamed A, Pantelic Milan V, Hearshen David, Chetty Indrin J, Movsas Benjamin, Wen Ning
Department of Radiation Oncology, Henry Ford Health System, Detroit, MI, 48202, USA.
Medical Physics Division, Department of Oncology, Wayne State University School of Medicine, Detroit, MI, 48201, USA.
Med Phys. 2020 Sep;47(9):4077-4086. doi: 10.1002/mp.14255. Epub 2020 Jun 12.
Deep learning models have had a great success in disease classifications using large data pools of skin cancer images or lung X-rays. However, data scarcity has been the roadblock of applying deep learning models directly on prostate multiparametric MRI (mpMRI). Although model interpretation has been heavily studied for natural images for the past few years, there has been a lack of interpretation of deep learning models trained on medical images. In this paper, an efficient convolutional neural network (CNN) was developed and the model interpretation at various convolutional layers was systematically analyzed to improve the understanding of how CNN interprets multimodality medical images and the predictive powers of features at each layer. The problem of small sample size was addressed by feeding the intermediate features into a traditional classification algorithm known as weighted extreme learning machine (wELM), with imbalanced distribution among output categories taken into consideration.
The training data collection used a retrospective set of prostate MR studies, from SPIE-AAPM-NCI PROSTATEx Challenges held in 2017. Three hundred twenty biopsy samples of lesions from 201 prostate cancer patients were diagnosed and identified as clinically significant (malignant) or not significant (benign). All studies included T2-weighted (T2W), proton density-weighted (PD-W), dynamic contrast enhanced (DCE) and diffusion-weighted (DW) imaging. After registration and lesion-based normalization, a CNN with four convolutional layers were developed and trained on tenfold cross validation. The features from intermediate layers were then extracted as input to wELM to test the discriminative power of each individual layer. The best performing model from the tenfolds was chosen to be tested on the holdout cohort from two sources. Feature maps after each convolutional layer were then visualized to monitor the trend, as the layer propagated. Scatter plotting was used to visualize the transformation of data distribution. Finally, a class activation map was generated to highlight the region of interest based on the model perspective.
Experimental trials indicated that the best input for CNN was a modality combination of T2W, apparent diffusion coefficient (ADC) and DWI . The convolutional features from CNN paired with a weighted extreme learning classifier showed substantial performance compared to a CNN end-to-end training model. The feature map visualization reveals similar findings on natural images where lower layers tend to learn lower level features such as edges, intensity changes, etc, while higher layers learn more abstract and task-related concept such as the lesion region. The generated saliency map revealed that the model was able to focus on the region of interest where the lesion resided and filter out background information, including prostate boundary, rectum, etc. CONCLUSIONS: This work designs a customized workflow for the small and imbalanced dataset of prostate mpMRI where features were extracted from a deep learning model and then analyzed by a traditional machine learning classifier. In addition, this work contributes to revealing how deep learning models interpret mpMRI for prostate cancer patient stratification.
深度学习模型在利用大量皮肤癌图像或肺部X光片数据池进行疾病分类方面取得了巨大成功。然而,数据稀缺一直是直接将深度学习模型应用于前列腺多参数磁共振成像(mpMRI)的障碍。尽管在过去几年中对自然图像的模型解释进行了大量研究,但对于基于医学图像训练的深度学习模型的解释却很少。在本文中,我们开发了一种高效的卷积神经网络(CNN),并系统地分析了各个卷积层的模型解释,以增进对CNN如何解释多模态医学图像以及每层特征预测能力的理解。通过将中间特征输入到一种称为加权极限学习机(wELM)的传统分类算法中,并考虑输出类别之间的不平衡分布,解决了小样本量的问题。
训练数据收集使用了2017年举办的SPIE-AAPM-NCI PROSTATEx挑战赛中的一组前列腺MR研究的回顾性数据集。对201例前列腺癌患者的320个病变活检样本进行诊断,并确定为具有临床意义(恶性)或无意义(良性)。所有研究均包括T2加权(T2W)、质子密度加权(PD-W)、动态对比增强(DCE)和扩散加权(DW)成像。在配准和基于病变的归一化之后,开发了一个具有四个卷积层的CNN,并在十折交叉验证上进行训练。然后提取中间层特征作为wELM的输入,以测试各层的判别能力。从十折中选择性能最佳的模型在来自两个来源的保留队列上进行测试。然后可视化每个卷积层后的特征图,以监测随着层的传播的趋势。使用散点图可视化数据分布的变化。最后,生成类激活图以基于模型视角突出显示感兴趣区域。
实验表明,CNN的最佳输入是T2W、表观扩散系数(ADC)和DWI的模态组合。与CNN端到端训练模型相比,CNN的卷积特征与加权极限学习分类器相结合表现出显著性能。特征图可视化在自然图像上显示了类似的结果,其中较低层倾向于学习较低级别的特征,如边缘、强度变化等,而较高层学习更抽象和与任务相关的概念,如病变区域。生成的显著性图表明,该模型能够聚焦于病变所在的感兴趣区域,并过滤掉背景信息,包括前列腺边界、直肠等。结论:这项工作为前列腺mpMRI的小样本和不平衡数据集设计了一种定制的工作流程,其中从深度学习模型中提取特征,然后由传统机器学习分类器进行分析。此外,这项工作有助于揭示深度学习模型如何解释mpMRI以进行前列腺癌患者分层。