Computational pathology: A survey review and the way forward.

Computational Pathology (CPath) is an interdisciplinary science that augments developments of computational approaches to analyze and model medical histopathology images. The main objective for CPath is to develop infrastructure and workflows of digital diagnostics as an assistive CAD system for clinical pathology, facilitating transformational changes in the diagnosis and treatment of cancer that are mainly address by CPath tools. With evergrowing developments in deep learning and computer vision algorithms, and the ease of the data flow from digital pathology, currently CPath is witnessing a paradigm shift. Despite the sheer volume of engineering and scientific works being introduced for cancer image analysis, there is still a considerable gap of adopting and integrating these algorithms in clinical practice. This raises a significant question regarding the direction and trends that are undertaken in CPath. In this article we provide a comprehensive review of more than 800 papers to address the challenges faced in problem design all-the-way to the application and implementation viewpoints. We have catalogued each paper into a model-card by examining the key works and challenges faced to layout the current landscape in CPath. We hope this helps the community to locate relevant works and facilitate understanding of the field's future directions. In a nutshell, we oversee the CPath developments in cycle of stages which are required to be cohesively linked together to address the challenges associated with such multidisciplinary science. We overview this cycle from different perspectives of data-centric, model-centric, and application-centric problems. We finally sketch remaining challenges and provide directions for future technical developments and clinical integration of CPath. For updated information on this survey review paper and accessing to the original model cards repository, please refer to GitHub. Updated version of this draft can also be found from arXiv.

Focus Quality Assessment of High-Throughput Whole Slide Imaging in Digital Pathology.

One of the challenges facing the adoption of digital pathology workflows for clinical use is the need for automated quality control. As the scanners sometimes determine focus inaccurately, the resultant image blur deteriorates the scanned slide to the point of being unusable. Also, the scanned slide images tend to be extremely large when scanned at greater or equal 20X image resolution. Hence, for digital pathology to be clinically useful, it is necessary to use computational tools to quickly and accurately quantify the image focus quality and determine whether an image needs to be re-scanned. We propose a no-reference focus quality assessment metric specifically for digital pathology images that operate by using a sum of even-derivative filter bases to synthesize a human visual system-like kernel, which is modeled as the inverse of the lens' point spread function. This kernel is then applied to a digital pathology image to modify high-frequency image information deteriorated by the scanner's optics and quantify the focus quality at the patch level. We show in several experiments that our method correlates better with ground-truth z -level data than other methods, which is more computationally efficient. We also extend our method to generate a local slide-level focus quality heatmap, which can be used for automated slide quality control, and demonstrate the utility of our method for clinical scan quality control by comparison with subjective slide quality scores.

Convolutional Deblurring for Natural Imaging.

In this paper, we propose a novel design of image deblurring in the form of one-shot convolution filtering that can directly convolve with naturally blurred images for restoration. The problem of optical blurring is a common disadvantage to many imaging applications that suffer from optical imperfections. Despite numerous deconvolution methods that blindly estimate blurring in either inclusive or exclusive forms, they are practically challenging due to high computational cost and low image reconstruction quality. Both conditions of high accuracy and high speed are prerequisites for high-throughput imaging platforms in digital archiving. In such platforms, deblurring is required after image acquisition before being stored, previewed, or processed for high-level interpretation. Therefore, on-the-fly correction of such images is important to avoid possible time delays, mitigate computational expenses, and increase image perception quality. We bridge this gap by synthesizing a deconvolution kernel as a linear combination of finite impulse response (FIR) even-derivative filters that can be directly convolved with blurry input images to boost the frequency fall-off of the point spread function (PSF) associated with the optical blur. We employ a Gaussian low-pass filter to decouple the image denoising problem for image edge deblurring. Furthermore, we propose a blind approach to estimate the PSF statistics for two Gaussian and Laplacian models that are common in many imaging pipelines. Thorough experiments are designed to test and validate the efficiency of the proposed method using 2054 naturally blurred images across six imaging applications and seven state-of-the-art deconvolution methods.

Encoding Visual Sensitivity by MaxPol Convolution Filters for Image Sharpness Assessment.

In this paper, we propose a novel design of Human Visual System (HVS) response in a convolutional filter form to decompose meaningful features that are closely tied with image sharpness level. No-reference (NR) Image sharpness assessment (ISA) techniques have emerged as the standard of image quality assessment in diverse imaging applications. Despite their high correlation with subjective scoring, they are challenging for practical considerations due to high computational cost and lack of scalability across different image blurs. We bridge this gap by synthesizing the HVS response as a linear combination of Finite Impulse Response (FIR) derivative filters to boost the falloff of high band frequency magnitudes in natural imaging paradigm. The numerical implementation of the HVS filter is carried out with MaxPol filter library that can be arbitrarily set for any differential orders and cutoff frequencies to balance out the estimation of informative features and noise sensitivities. Utilized by HVS filter, we then design an innovative NR-ISA metric called "HVS-MaxPol" that (a) requires minimal computational cost, (b) produce high correlation accuracy with image sharpness level, and (c) scales to assess synthetic and natural image blur. Specifically, the synthetic blur images are constructed by blurring the raw images using Gaussian filter, while natural blur is observed from real-life application such as motion, out-of-focus, luminance contrast, etc. Furthermore, we create a natural benchmark database in digital pathology for validation of image focus quality in whole slide imaging systems called "FocusPath" consisting of 864 blurred images. Thorough experiments are designed to test and validate the efficiency of HVS-MaxPol across different blur databases and state-of-the-art NR-ISA metrics. The experiment result indicates that our metric has the best overall performance with respect to speed, accuracy and scalability.

Derivative Kernels: Numerics and Applications.

A generalized framework for numerical differentiation (ND) is proposed for constructing a finite impulse response (FIR) filter in closed form. The framework regulates the frequency response of ND filters for arbitrary derivative-order and cutoff frequency selected parameters relying on interpolating power polynomials and maximally flat design techniques. Compared with the state-of-the-art solutions, such as Gaussian kernels, the proposed ND filter is sharply localized in the Fourier domain with ripple-free artifacts. Here, we construct 2D MaxFlat kernels for image directional differentiation to calculate image differentials for arbitrary derivative order, cutoff level and steering angle. The resulted kernel library renders a new solution capable of delivering discrete approximation of gradients, Hessian, and higher-order tensors in numerous applications. We tested the utility of this library on three different imaging applications with main focus on the unsharp masking. The reported results highlight the high efficiency of the 2D MaxFlat kernel and its versatility with respect to robustness and parameter control accuracy.

High-accuracy total variation with application to compressed video sensing.

Numerous total variation (TV) regularizers, engaged in image restoration problem, encode the gradients by means of simple [-1, 1] finite-impulse-response (FIR) filter. Despite its low computational processing, this filter severely distorts signal's high-frequency components pertinent to edge/ discontinuous information and cause several deficiency issues known as texture and geometric loss. This paper addresses this problem by proposing an alternative model to the TV regularization problem via high-order accuracy differential FIR filters to preserve rapid transitions in signal recovery. A numerical encoding scheme is designed to extend the TV model into multidimensional representation (tensorial decomposition). We adopt this design to regulate the spatial and temporal redundancy in compressed video sensing problem to jointly recover frames from undersampled measurements. We then seek the solution via alternating direction methods of multipliers and find a unique solution to quadratic minimization step with capability of handling different boundary conditions. The resulting algorithm uses much lower sampling rate and highly outperforms alternative state-of-the-art methods. This is evaluated both in terms of restoration accuracy and visual quality of the recovered frames.