Evolutionary Strategies AI Addresses Multiple Technical Challenges in Deep Learning Deployment: Proof-of-Principle Demonstration for Neuroblastoma Brain Metastasis Detection.

Two significant obstacles hinder the advancement of Radiology AI. The first is the challenge of overfitting, where small training data sets can result in unreliable outcomes. The second challenge is the need for more generalizability, the lack of which creates difficulties in implementing the technology across various institutions and practices. A recent innovation, deep neuroevolution (DNE), has been introduced to tackle the overfitting issue by training on small data sets and producing accurate predictions. However, the generalizability of DNE has yet to be proven. This paper strives to overcome this barrier by demonstrating that DNE can achieve satisfactory results in diverse external validation sets. The main innovation of the work is thus showing that DNE can generalize to varied outside data. Our example use case is predicting brain metastasis from neuroblastoma, emphasizing the importance of AI with limited data sets. Despite image collection and labeling advancements, rare diseases will always constrain data availability. We optimized a convolutional neural network (CNN) with DNE to demonstrate generalizability. We trained the CNN with 60 MRI images and tested it on a separate diverse collection of images from over 50 institutions. For comparison, we also trained with the more traditional stochastic gradient descent (SGD) method, with the two variants of (1) training from scratch and (2) transfer learning. Our results show that DNE demonstrates excellent generalizability with 97% accuracy on the heterogeneous testing set, while neither form of SGD could reach 60% accuracy. DNE's ability to generalize from small training sets to external and diverse testing sets suggests that it or similar approaches may play an integral role in improving the clinical performance of AI.

Direct Evaluation of Treatment Response in Brain Metastatic Disease with Deep Neuroevolution.

Cancer centers have an urgent and unmet clinical and research need for AI that can guide patient management. A core component of advancing cancer treatment research is assessing response to therapy. Doing so by hand, for example, as per RECIST or RANO criteria, is tedious and time-consuming, and can miss important tumor response information. Most notably, the prevalent response criteria often exclude lesions, the non-target lesions, altogether. We wish to assess change in a holistic fashion that includes all lesions, obtaining simple, informative, and automated assessments of tumor progression or regression. Because genetic sub-types of cancer can be fairly specific and patient enrollment in therapy trials is often limited in number and accrual rate, we wish to make response assessments with small training sets. Deep neuroevolution (DNE) is a novel radiology artificial intelligence (AI) optimization approach that performs well on small training sets. Here, we use a DNE parameter search to optimize a convolutional neural network (CNN) that predicts progression versus regression of metastatic brain disease. We analyzed 50 pairs of MRI contrast-enhanced images as our training set. Half of these pairs, separated in time, qualified as disease progression, while the other 25 image pairs constituted regression. We trained the parameters of a CNN via "mutations" that consisted of random CNN weight adjustments and evaluated mutation "fitness" as summed training set accuracy. We then incorporated the best mutations into the next generation's CNN, repeating this process for approximately 50,000 generations. We applied the CNNs to our training set, as well as a separate testing set with the same class balance of 25 progression and 25 regression cases. DNE achieved monotonic convergence to 100% training set accuracy. DNE also converged monotonically to 100% testing set accuracy. We have thus shown that DNE can accurately classify brain metastatic disease progression versus regression. Future work will extend the input from 2D image slices to full 3D volumes, and include the category of "no change." We believe that an approach such as ours can ultimately provide a useful and informative complement to RANO/RECIST assessment and volumetric AI analysis.

Integrating Eye Tracking and Speech Recognition Accurately Annotates MR Brain Images for Deep Learning: Proof of Principle.

PURPOSE: To generate and assess an algorithm combining eye tracking and speech recognition to extract brain lesion location labels automatically for deep learning (DL). MATERIALS AND METHODS: In this retrospective study, 700 two-dimensional brain tumor MRI scans from the Brain Tumor Segmentation database were clinically interpreted. For each image, a single radiologist dictated a standard phrase describing the lesion into a microphone, simulating clinical interpretation. Eye-tracking data were recorded simultaneously. Using speech recognition, gaze points corresponding to each lesion were obtained. Lesion locations were used to train a keypoint detection convolutional neural network to find new lesions. A network was trained to localize lesions for an independent test set of 85 images. The statistical measure to evaluate our method was percent accuracy. RESULTS: Eye tracking with speech recognition was 92% accurate in labeling lesion locations from the training dataset, thereby demonstrating that fully simulated interpretation can yield reliable tumor location labels. These labels became those that were used to train the DL network. The detection network trained on these labels predicted lesion location of a separate testing set with 85% accuracy. CONCLUSION: The DL network was able to locate brain tumors on the basis of training data that were labeled automatically from simulated clinical image interpretation.© RSNA, 2020.

A threshold-based method to predict thyroid nodules on scintigraphy scans.

Nuclear Medicine imaging is an important modality to follow up abnormalities of thyroid function tests and to uncover and characterize thyroid nodules either de novo or as previously seen on other imaging modalities, namely ultrasound. In general, the hypofunctioning 'cold' nodules pose a higher malignancy potential than hyperfunctioning 'hot' nodules, for which the risk is <1%. Hot nodules are detected by the radiologist as a region of focal increased radiotracer uptake, which appears as a density of pixels that is higher than surrounding normal thyroid parenchyma. Similarly, cold nodules show decreased density of pixels, corresponding to their decreased uptake of radiotracer, and are photopenic. Partly because Nuclear Medicine images have poor resolution, these density variations can sometimes be subtle, and a second reader computer-aided detection (CAD) scheme that can highlight hot/cold nodules has the potential to reduce false negatives by bringing the radiologists' attention to the occasional overlooked nodules. Our approach subdivides thyroid images into small regions and employs a set of pixel density cutoffs, marking regions that fulfill density criteria. Thresholding is a fundamental tool in image processing. In nuclear medicine, scroll bars to adjust standardized uptake value cutoffs are already in wide commercial use in PET/CT display systems. A similar system could be used for planar thyroid images, whereby the user varies threshold and highlights suspect regions after an initial reader survey of the images. We hypothesized that a thresholding approach would accurately detect both hot and cold thyroid nodules relative to expert readers. Analyzing 22 nodules, half of them hot and the other half cold, we found good agreement between highlighted candidate nodules and the consensus selections of two expert readers, with nonzero overlap between expert and CAD selections in all cases.

The normal mode analysis shape detection method for automated shape determination of lung nodules.

Surface morphology and shape in general are important predictors for the behavior of solid-type lung nodules detected on CT. More broadly, shape analysis is useful in many areas of computer-aided diagnosis and essentially all scientific and engineering disciplines. Automated methods for shape detection have all previously, to the author's knowledge, relied on some sort of geometric measure. I introduce Normal Mode Analysis Shape Detection (NMA-SD), an approach that measures shape indirectly via the motion it would undergo if one imagined the shape to be a pseudomolecule. NMA-SD allows users to visualize internal movements in the imaging object and thereby develop an intuition for which motions are important, and which geometric features give rise to them. This can guide the identification of appropriate classification features to distinguish among classes of interest. I employ normal mode analysis (NMA) to animate pseudomolecules representing simulated lung nodules. Doing so, I am able to assign a testing set of nodules into the classes circular, elliptical, and irregular with roughly 97 % accuracy. This represents a proof-of-principle that one can obtain shape information by treating voxels as pseudoatoms in a pseudomolecule, and analyzing the pseudomolecule's predicted motion.

Pilot study of a novel tool for input-free automated identification of transition zone prostate tumors using T2- and diffusion-weighted signal and textural features.

PURPOSE: To present results of a pilot study to develop software that identifies regions suspicious for prostate transition zone (TZ) tumor, free of user input. MATERIALS AND METHODS: Eight patients with TZ tumors were used to develop the model by training a Naïve Bayes classifier to detect tumors based on selection of most accurate predictors among various signal and textural features on T2-weighted imaging (T2WI) and apparent diffusion coefficient (ADC) maps. Features tested as inputs were: average signal, signal standard deviation, energy, contrast, correlation, homogeneity and entropy (all defined on T2WI); and average ADC. A forward selection scheme was used on the remaining 20% of training set supervoxels to identify important inputs. The trained model was tested on a different set of ten patients, half with TZ tumors. RESULTS: In training cases, the software tiled the TZ with 4 × 4-voxel "supervoxels," 80% of which were used to train the classifier. Each of 100 iterations selected T2WI energy and average ADC, which therefore were deemed the optimal model input. The two-feature model was applied blindly to the separate set of test patients, again without operator input of suspicious foci. The software correctly predicted presence or absence of TZ tumor in all test patients. Furthermore, locations of predicted tumors corresponded spatially with locations of biopsies that had confirmed their presence. CONCLUSION: Preliminary findings suggest that this tool has potential to accurately predict TZ tumor presence and location, without operator input.

A case of colorectal cancer with metastasis to the chest wall and subsequent hematoma formation.

We report a rare case of a patient with colorectal cancer with chest wall metastases. The development of bleeding at the site of the metastasis ultimately resulted in the development of a hematoma, necessitating resection of the tumor along with part of the chest wall. Literature on chest wall metastases of colonic adenocarcinoma is reviewed and discussed. The teaching point is that a chest wall mass seen on imaging should prompt consideration of metastatic cancer in the differential diagnosis. The colon is a rare though reported primary site.

The self-overlap method for assessment of lung nodule morphology in chest CT.

Surface morphology is an important indicator of malignant potential for solid-type lung nodules detected at CT, but is difficult to assess subjectively. Automated methods for morphology assessment have previously been described using a common measure of nodule shape, representative of the broad class of existing methods, termed area-to-perimeter-length ratio (APR). APR is static and thus highly susceptible to alterations by random noise and artifacts in image acquisition. We introduce and analyze the self-overlap (SO) method as a dynamic automated morphology detection scheme. SO measures the degree of change of nodule masks upon Gaussian blurring. We hypothesized that this new metric would afford equally high accuracy and superior precision than APR. Application of the two methods to a set of 119 patient lung nodules and a set of simulation nodules showed our approach to be slightly more accurate and on the order of ten times as precise, respectively. The dynamic quality of this new automated metric renders it less sensitive to image noise and artifacts than APR, and as such, SO is a potentially useful measure of cancer risk for solid-type lung nodules detected on CT.

Bend-twist-stretch model for coarse elastic network simulation of biomolecular motion.

The empirical harmonic potential function of elastic network models (ENMs) is augmented by three- and four-body interactions as well as by a parameter-free connection rule. In the new bend-twist-stretch (BTS) model the complexity of the parametrization is shifted from the spatial level of detail to the potential function, enabling an arbitrary coarse graining of the network. Compared to distance cutoff-based Hookean springs, the approach yields a more stable parametrization of coarse-grained ENMs for biomolecular dynamics. Traditional ENMs give rise to unbounded zero-frequency vibrations when (pseudo)atoms are connected to fewer than three neighbors. A large cutoff is therefore chosen in an ENM (about twice the average nearest-neighbor distance), resulting in many false-positive connections that reduce the spatial detail that can be resolved. More importantly, the required three-neighbor connectedness also limits the coarse graining, i.e., the network must be dense, even in the case of low-resolution structures that exhibit few spatial features. The new BTS model achieves such coarse graining by extending the ENM potential to include three-and four-atom interactions (bending and twisting, respectively) in addition to the traditional two-atom stretching. Thus, the BTS model enables reliable modeling of any three-dimensional graph irrespective of the atom connectedness. The additional potential terms were parametrized using continuum elastic theory of elastic rods, and the distance cutoff was replaced by a competitive Hebb connection rule, setting all free parameters in the model. We validate the approach on a carbon-alpha representation of adenylate kinase and illustrate its use with electron microscopy maps of E. coli RNA polymerase, E. coli ribosome, and eukaryotic chaperonin containing T-complex polypeptide 1, which were difficult to model with traditional ENMs. For adenylate kinase, we find excellent reproduction (>90% overlap) of the ENM modes and B factors when BTS is applied to the carbon-alpha representation as well as to coarser descriptions. For the volumetric maps, coarse BTS yields similar motions (70%-90% overlap) to those obtained from significantly denser representations with ENM. Our Python-based algorithms of ENM and BTS implementations are freely available.