Convolutional Neural Networks (CNNs) have revolutionized the fields of computer vision, machine and automation, achieving remarkable performance on previously-difficult tasks such as image classification, semantic segmentation, and depth estimation.(Shin et al., 2016; Greenspan et al., 2016; Shen et al., 2017; Zhang et al., 2017)
. CNNs are particularly powerful in supervised learning tasks where it is difficult to build an accurate mathematical model for the task at hand. With recent improvements made in training CNNs such as utilizing dropout regularization, skip connections and the advancements made in high-performance computing due to graphical processing units(LeCun et al., 2015; Goodfellow et al., 2016), deep learning models have become much easier to train and vastly more accessible.
To achieve generalization, deep learning models require large amounts of data that are accurately annotated. Obtaining such a dataset for a variety of medical images is challenging because expert annotation can be expensive, time consuming (Gur et al., 2017; Moradi et al., 2016), and often limited by the subjective interpretation (Kerkhof et al., 2007). Moreover, other issues such as privacy and under-representation of rare conditions impede developing such datasets (Wong et al., 2017; Schlegl et al., 2017). This is supplemented with the cross-patient adaptability problem, where networks trained on data from one patient fail to adapt to another patient (Reiter et al., 2016; Mahmood et al., 2018). For medical diagnostics, physicians are interested in diagnostic information which is common across patients rather than patient-specific information.
1.1 Training with Synthetic Medical Images
Recently, the limited availability of medical data has been addressed by the use of synthetic data (Mahmood and Durr, 2018a; Mahmood et al., 2018; Mahmood and Durr, 2018b). Computer graphics engines such as Blender and Unreal have the ability to construct realistic virtual worlds, but are limited by the diversity of 3D assets to create accurate, tissue-equivalent models (Zhang and Yuille, 2016). Other methods for synthetic data generation include Generative Adversarial Networks (GANs), which train a generative deep network to learn and sample a target distribution of realistic images (Goodfellow et al., 2014). This approach, however, suffers from the mode collapse problem, a commonly encountered failure case in GANs where the support size of the learned distribution is low, and thus, the generated images are sampled with low variability (Creswell et al., 2018). Overall, networks trained on synthetic data often fail to generalize to real data, as both of these approaches in synthetic data generation fail to produce realistic, diverse examples necessary for training deep networks in medical images (Mahmood et al., 2018). Cinematic rendering is a recently developed visualization technique that works by simulating the propagation and interaction of light passing through tissue models reconstructed from cross-sectional images such as CT, enabling the generation of photorealistic images that have not previously been possible (Eid et al., 2017). In this paper, we use cinematic rendering to generate a wide range of healthy to pathologic colon tissue with ground truth depth, and fine-tune synthetic data-driven networks with these images to address the problem of the cross-patient adaptability in training deep networks. To our knowledge, this is the first application of cinematic rendering in deep learning for medical image analysis. We test this method for monocular depth estimation in endoscopy, a task with many clinical applications (Durr et al., 2014b) but is challenging to acquire accurately.
1.2 Fine-Tuning Deep Networks
CNNs are trained by solving a typically non-convex error function using local search algorithms such as stochastic gradient descent and other optimizations. Beginning with randomly initialized weights, CNNs seek to minimize their empirical risk over the training dataset by iteratively updating the network parameters in the opposite direction of its error gradient, such that the network’s performance converges towards a minimum on the loss surface(Bottou, 2010). With limited data, poor initialization, and a lack of regularization to control capacity, the network may fail to generalize, and convergence can become slow when traversing saddle points and also lead to sub-optimal local minima (Neyshabur et al., 2017; Choromanska et al., 2015; Zhang et al., 2016; Dauphin et al., 2014; Samala et al., 2018). Initializing weights from a CNN trained for a similar task with a much larger dataset however, allows the network to converge much more easily to a good local minima and necessitates less labeled data (Glorot and Bengio, 2010). This process is called transfer learning, and is widely used in classification and segmentation tasks such as lesion detection in medical imaging, where there exists a paucity of annotated data (Penatti et al., 2015; Azizpour et al., 2015; Girshick et al., 2014; Sonntag et al., 2017; Zhen et al., 2017; Samala et al., 2017). In practice, transfer learning involves transferring weights from an existing network trained on a much larger dataset. For networks trained on similar tasks and datasets, the new network would freeze the first few layers, and train the remaining layers at a low learning rate. This process is called fine-tuning. Intuitively, the first few layers of a CNN hold low-level features that are shared across all types of images, and the last layers hold high-level features that are learned for a specific application (Tajbakhsh et al., 2016; Zhou et al., 2017; Samala et al., 2017). In this specific context, we hypothesize that networks trained on synthetic medical data, that might not have previously adapted to real data, would generalize better if fine-tuned using cinematically rendered photorealistic data. We further hypothesize that such fine-tuned networks require less amount of training data, and would work well in low-resource settings such as endoscopy.
1.3 Depth Estimation for Endoscopy
For the purpose of validating our hypotheses we focus on the task of depth estimation from monocular endoscopy images. Monocular depth estimation from endoscopy is a challenging problem and has a variety of clinical applications including topographical reconstruction of the lumen, image-guided surgery, endoscopy quality metrics, and enhanced polyp detection, as polyps can lie on convex surfaces and can be occluded by folds in the gastrointestinal tract (Hazirbas et al., 2016; Zhu et al., 2010; Wang et al., 2015). Depth estimation is especially challenging because the tissue being imaged is often deformable, and endoscopes have a single camera with close light sources and a wide field of view. Current approaches either have limited accuracy due to restrictive assumptions (Hong et al., 2014) or require modifying endoscope hardware which has significant regulatory and engineering barriers (Parot et al., 2013; Durr et al., 2014a). Data-driven approaches for depth estimation in endoscopy are additionally complicated because of the lack of clinical images with available ground truth data, since it is difficult to include a depth sensor on an endoscope (Nadeem and Kaufman, 2016). Moreover, networks trained on data from one patient fail to generalize to other patients since they start learning from patient-specific texture and color. Previous work has focused on generating synthetic data and adversarial domain adaptation to overcome these issues (Mahmood and Durr, 2018a; Mahmood et al., 2018). In this paper, we will focus on using synthetic endoscopy data with ground truth depth for training and fine-tuning using photorealistic cinematically rendered data.
2.1 Endoscopy Depth Dataset Generation
We generated three different datasets of endoscopy images with ground truth depth for three different purposes: (a) a large dataset of synthetic endoscopy images for training, (b) a small dataset of cinematically rendered images for fine-tuning, and (c) a small dataset of real endoscopy images of a porcine colon for validation.
2.1.1 Synthetic Endoscopy Data for Training
Though synthetic data has been extensively used to train deep CNN models for real-world images (Su et al., 2015; Gupta et al., 2016; Varol et al., 2017; Planche et al., 2017), this approach has been relatively limited for medical imaging.
Recent work in generating synthetic data for medical images have been applying GANs to retinal images and histopathology images (Costa et al., 2017). However, GAN-synthesized medical data does not cater for the cross-patient adaptability problem. In general, synthetic medical imaging data can be generated given an anatomically correct organ model and a forward model of an imaging device (Fig. 1-Top). Forward models for diagnostic imaging devices are more complicated than typical cameras and anatomic models of organs need to represent a high degree of variation. We developed a forward model of an endoscope with a wide-angle monocular camera and two to three light sources that exhibit realistic inverse square law of intensity fall-off. We use a synthetically-generated and anatomically accurate colon model and image it using the virtual endoscope placed at a variety of angles and varying conditions to mimic the movement of an actual endoscope. We also generate pixel-wise ground truth depth for each rendered image. Using this model, we generated a dataset of 200,000 grayscale endoscopy images, each with a corresponding, error-free ground truth depth map (Fig. 1-Top, Fig. 2).
2.2 Cinematically Rendered Data for Fine-Tuning
While synthetic endoscopy data models the inverse of intensity fall off with depth, it conventionally only considers the surface of the rendered object—it does not simulate light scattering and extinction through turbid media. Moreover, conventional synthetic rendering does not simulate high frequency details in the colon such as texture and color. A model trained on data from one source is often incapable of performing well on a target domain due to distinctions in the distributions of these two domains. Models trained on synthetic data would have a domain bias towards synthetic images, and would not cover the distribution of testing cases found in real patient data. The Cinematic VRT technology developed at Siemens Healthcare provides a natural and photorealistic 3D representation of medical scans, such as Computed Tomography (CT) or Magnetic Resonance Images (MRI) (Comaniciu et al., 2016; Dappa et al., 2016). The cinematic rendering process is computationally complex and depending on the image size it can take to seconds per image (Dappa et al., 2016). Cinematic rendered data covers the testing use cases better than synthetic data. Our fine-tuning approach prevents the network from learning patient-specific features by assigning the same depth to four different cinematic renderings. By including renderings of the same colon image with different colors and textures in the training set, the network can learn more domain-invariant features, which would allow it to generalize well to other tissue models.
The physical rendering algorithm, based on a Monte Carlo path-tracing technique closely simulates the complex interaction of light rays with tissues found in the scanned volume. Compared to traditional volume ray casting, where only light emission and absorption along a straight ray is considered, path tracing considers light paths with multiple random scattering events and light extinction. Although this lighting model requires more computational power as hundreds of light paths must be calculated, it considerably enhances depth and shape perception. By putting the anatomical structures within the medical scans in a virtual lighting condition that mimics the physical lighting experienced in reality, soft shadows, ambient occlusions and volumetric scattering effects can be observed in the cinematic rendered images. Monte Carlo path tracing and interaction can be used to calculate the radiant flux, at a distance received from the direction along a ray using the following multidimensional rendering equation,
where, represents all possible light directions and D represents the maximum distance. The optical properties of the tissue under consideration are defined by , which describes the fraction of light traveling along a direction being scattered into direction is the radiance arriving at distance from direction . Surface interactions are modeled with a bidirectional reflectance distribution function (BRDF) and tissue scattering is modeled using a Henyey-Greenstein phase function (Toublanc, 1996). represents the optical depth and its corresponding excitation coefficient is represented by the sum of absorption and scattering coefficients, (Comaniciu et al., 2016). Compared to conventional medical rendering, this technique considerably enhances depth and shape perception by putting the anatomical structures within the medical scans in a virtual lighting condition that mimics the physical lighting experienced in reality. Cinematic rendering has been used for a variety of medical imaging visualization tasks (Johnson et al., 2017; Rowe et al., 2018b; Chu et al., 2018; Rowe et al., 2018a).
Using this Cinematic VRT technology, colonic images were generated together with their corresponding depth maps, by saving the gradient and the position of the rays once their accumulated opacity had reached a given threshold (Fig. 1-Middle). Four different sets of rendering parameters were used to generate a diverse set of renderings for each scene. This was done to prevent the network from learning texture and color in the renderings (Fig. 1-Middle, Fig. 2). We used a total of 1200 rendered images for fine-tuning from 300 different scenes. The CT colonoscopy data used was acquired from 9 patients from the NIH Cancer Imaging Archive (TCIA) (Johnson et al., 2008). Cinematic rendered data covers the testing use cases better than synthetic data, as it presents a possible solution to the domain adaptation problem with a more realistic forward model of the light-tissue interaction and by modeling both high frequency features and depth cues. Our fine-tuning approach prevents the network from learning patient-specific features by assigning the same depth to four different cinematic renderings. By including renderings of the same colon image with different colors and textures in the training set, the network can learn more domain-invariant features, which would allow it to generalize well to other tissue models.
2.3 Real Pig Colon Optical Endoscopy Data
To validate our approach, we tested the depth-estimation performance on a dataset of real endoscopy images. We created a dataset of ex-vivo pig colon optical endoscopy images with ground truth depth determined from CT. In particular, we fixed a porcine colon to a tubular scaffold and conducted optical endoscopy imaging using a Misumi Endoscope (MO-V5006L). Subsequently, we collected cone beam CT data from the same scaffold. A 3D model of this fixed colon was reconstructed using filtered-back projection with a Ram-Lak filter (Natterer, 1986). The reconstructed density was then imaged using a virtual endoscope with same camera parameters as the optical Misumi endoscope. The resulting virtual endoscopy images were registered to optical endoscopy views using a one-plus-one evolutionary optimizer (Styner et al., 2000; Zitzler et al., 2004). Once registered, the depth for each virtual endoscopy view was used as the depth for the corresponding optical endoscopy view (Fig.1-Bottom, Fig. 2).
2.4 Monocular Endoscopy Depth Estimation using CNN-CRF Joint Training
To train an endoscopy depth estimation network using synthetic data and fine-tuning using cinematically rendered data we used a joint CNN and Conditional Random Fields (CRF) network similar to the setup described in (Mahmood and Durr, 2018a; Liu et al., 2016). Intuitively, a CNN-CRF setup is more context-aware than a simple CNN, as it takes into account the smooth transitions and abrupt changes that are characteristic of an endoscopy depth map. Assuming is an endoscopy image which has been divided into super-pixels, , and
where, is the energy CRF function. In order to predict the depth of a new image we need to solve a maximum aposteriori (MAP) problem, .
Let and be unary and pairwise potentials over nodes and edges of . Where, predicts the depth from a single superpixel and encourages smoothness between neighboring pairwise superpixels. The two potentials must be learned in a single unified framework. Based on (Liu et al., 2016; Mahmood and Durr, 2018a) the unary potential can be defined as,
where is the depth of a superpixel and represents CNN parameters. The pairwise potential function is based on standard CRF vertex and edge feature functions studied extensively in (Qin et al., 2009) and other works. Let be the parameters of the network and be the similarity index matrix where represents a metric between the and super-pixel. In this case, we used intensity and greyscale histogram as pairwise similarities which were expressed in form. The pairwise potential can then be simply written as,
Simplifying the energy function,
During training, the negative log likelihood of the probability density function which can be derived from Eq. 1 is minimized with respect to the two learning parameters. Regularization termsare added to the objective function to suppress heavily weighted vectors. Let be the number of images in the training data then the objective function can be stated as,
This optimization problem is solved using stochastic gradient decent-based back propagation. Our network operates for the unary part on a superpixel patch level and is composed of 5 convolutional and 4 fully connected layers (Fig. 3). The fully connected layers are fine-tuned using cinematically rendered data. The pairwise part operates on similarity
similarity metrics between neighboring superpixels based on intensity and grayscale histogram followed by a fully connected layer. The network architecture is illustrated in Fig. 3. The network was initially trained on gray scale synthetic images with three channels, each channel assigned the same grayscale value. The network is then fine-tuned with color RGB cinematically rendered data. The network was trained using MatConvNet with Matlab 2017b. The momentum was set to 0.8 and the weight decay parameters were set to 0.0005. The network was trained for 200 epochs and the learning rate was set to 0.0002 and linearly decreased after the first 20 epochs. All parameters were tuned on synthetic data and cinematically rendered data, none of the real endoscopy test images were used for training or parameter tuning.
3.1 Quantitative Evaluation
We evaluated based on metrics our depth estimation paradigm and the capability of fine-tuning using the following metrics:
Relative Error (rel):
Average Error ():
Root Mean Square Error (rms):
Where is the ground truth depth is the estimated depth and is the total number of samples. Table 1 and 2 and Fig. 4 show results based on these metrics for cinematically data and porcine colon real endoscopy data. None of the test data was or images within the close proximity were used for training. Tables I and II validate our hypotheses that CNN-CRF fine-tuned networks (CNN-CRF-FT) works better than networks trained only on synthetic data and that a smaller amount of data is required for initial full training if the last layers are fine-tuned. We also observed that fine-tuning with four renderings of a scene improved performance over fine-tuning with just one rendering (Table 2). This is because in supplying multiple renderings of the same scene with the same depth map, the CNN-CRF was able to better learn the context-aware features for depth estimation such as intensity differences between superpixels, and overcome noisy details such as texture or color. As a result, the network was able to work well on real data such as the pig colon data used in this study. Table 3 shows that fine-tuning with just images from one kind of rendering gives a worse result compared to fine-tuning with images each from four different kinds of renderings. Our experimentation demonstrated that training with only cinematically rendered data resulted in overfitting to high frequency features of the data. We found that training on synthetic data with lower frequency details and fine tuning on cinematically rendered data worked much better.
Despite the recent advances in computer vision and deep learning algorithms, their applicability to medical images is often limited by the scarcity of annotated data. The problem is further complicated by the underrepresentation of rare conditions. For example, getting annotated data for polyp localization is difficult because in a 20 minute colonoscopy examination of the 1.5 meter colon, only a few 10 mm polyps may be present. Depending on the field-of-view of the camera, the polyps may also be occluded by folds in the gastrointestinal tract (Wang et al., 2015). Using depth with RGB images has shown to improve localization in natural scenes by helping recover rich structural information with less annotated data and better cross-dataset adaptability (Hazirbas et al., 2016).
Within the constrained setting of endoscopy, estimating depth from monocular views is difficult because ground truth depth is hard to acquire. Problems where ground truth is difficult or impossible to acquire have been tackled for natural scenes by generating synthetic data. However, there are few examples of synthetic data driven medical imaging applications (Mahmood et al., 2018; Mahmood and Durr, 2018a; Nie et al., 2017). This is because synthetic data-driven models often fail to generalize to the real datasets, and is often complimented by the cross patient network adaptability problem, where networks that work well on one patient do not generalize to other patients.
In this work, we demonstrate one of the first successful uses of cinematically rendered data for generalizing a network trained on synthetic data to real data. Additionally, our approach successfully addresses the issue of the domain adaptation or cross-patient network adaptability. We show that a synthetic data-driven CNN-CRF model can be successfully trained for accurate depth estimation on real tissue given no real optical endoscopy training data. Moreover, we prevent the network from learning from texture or color by providing the network with a variety of renderings assigned to the same depth value. We observed that depth estimation accuracy increases when trained with a variety of renderings for the same scene. We believe this improvement is due to the multiple rendering facilitating the networking learning to predict depth from cues that are invariant among different patients such as colon shape and light intensity fall-off with depth.
The shortcomings of this method include errors and artifacts in CT rendering. Unlike the synthetic data the ground truth for rendered CT data suffers from errors due to CT reconstruction artifacts, resolution limits, and imperfect registration. This error can be propagated in the learning process when fine-tuning with cinematically rendered data and when evaluating our model with real endoscopy data registered to CT.
Beyond accurate depth estimation, future work will investigate semantic segmentation in endoscopy by fusing depth as an additional input (Hazirbas et al., 2016). Our future work will also focus on generalizing this concept to other medical imaging modalities.
The authors would like to thank Sermet Onel for his help with internal lighting and Kaloian Petkov for his help with multiple aspects of the cinematic renderer.
This feature is based on research, and is not commercially available. Due to regulatory reasons its future availability cannot be guaranteed.
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