Evaluation of commercially available point-of-care ultrasound for automated optic nerve sheath measurement.

BACKGROUND: Measurement of the optic nerve sheath diameter (ONSD) via ultrasonography has been proposed as a non-invasive metric of intracranial pressure that may be employed during in-field patient triage. However, first responders are not typically trained to conduct sonographic exams and/or do not have access to an expensive ultrasound device. Therefore, for successful deployment of ONSD measurement in-field, we believe that first responders must have access to low-cost, portable ultrasound and be assisted by artificial intelligence (AI) systems that can automatically interpret the optic nerve sheath ultrasound scan. We examine the suitability of five commercially available, low-cost, portable ultrasound devices that can be combined with future artificial intelligence algorithms to reduce the training required for and cost of in-field optic nerve sheath diameter measurement. This paper is focused on the quality of the images generated by these low-cost probes. We report results of a clinician preference survey and compare with a lab analysis of three quantitative image quality metrics across devices. We also examine the suitability of the devices in a hypothetical far-forward deployment using operators unskilled in ultrasound, with the assumption of a future onboard AI video interpreter. RESULTS: We find statistically significant differences in clinician ranking of the devices in the following categories: "Image Quality", "Ease of Acquisition", "Software", and "Overall ONSD". We show differences in signal-to-noise ratio, generalized contrast-to-noise ratio, point-spread function across the devices. These differences in image quality result in a statistically significant difference in manual ONSD measurement. Finally, we show that sufficiently wide transducers can capture the optic nerve sheath during blind (no visible B-mode) scans performed by operators unskilled in sonography. CONCLUSIONS: Ultrasound of the optic nerve sheath has the potential to be a convenient, non-invasive, point-of-injury or triage measure for elevated intracranial pressure in cases of traumatic brain injury. When transducer width is sufficient, briefly trained operators may obtain video sequences of the optic nerve sheath without guidance. This data suggest that unskilled operators are able to achieve the images needed for AI interpretation. However, we also show that image quality differences between ultrasound probes may influence manual ONSD measurements.

Interactive, in-browser cinematic volume rendering of medical images.

The diversity and utility of cinematic volume rendering (CVR) for medical image visualization have grown rapidly in recent years. At the same time, volume rendering on augmented and virtual reality systems is attracting greater interest with the advance of the WebXR standard. This paper introduces CVR extensions to the open-source visualization toolkit (vtk.js) that supports WebXR. This paper also summarizes two studies that were conducted to evaluate the speed and quality of various CVR techniques on a variety of medical data. This work is intended to provide the first open-source solution for CVR that can be used for in-browser rendering as well as for WebXR research and applications. This paper aims to help medical imaging researchers and developers make more informed decision when selecting CVR algorithms for their applications. Our software and this paper also provide a foundation for new research and product development at the intersection of medical imaging, web visualization, XR, and CVR.

Detection of pneumothorax on ultrasound using artificial intelligence.

BACKGROUND: Ultrasound (US) for the detection of pneumothorax shows excellent sensitivity in the hands of skilled providers. Artificial intelligence may facilitate the movement of US for pneumothorax into the prehospital setting. The large amount of training data required for conventional neural network methodologies has limited their use in US so far. METHODS: A limited training database was supplied by Defense Advanced Research Projects Agency of 30 patients, 15 cases with pneumothorax and 15 cases without. There were two US videos per patient, of which we were allowed to choose one to train on, so that a limited set of 30 videos were used. Images were annotated for ribs and pleural interface. The software performed anatomic reconstruction to identify the region of interest bounding the pleura. Three neural networks were created to analyze images on a pixel-by-pixel fashion with direct voting determining the outcome. Independent verification and validation was performed on a data set gathered by the Department of Defense. RESULTS: Anatomic reconstruction with the identification of ribs and pleura was able to be accomplished on all images. On independent verification and validation against the Department of Defense testing data, our program concurred with the SME 80% of the time and achieved a 86% sensitivity (18/21) for pneumothorax and a 75% specificity for the absence of pneumothorax (18/24). Some of the mistakes by our artificial intelligence can be explained by chest wall motion, hepatization of the underlying lung, or being equivocal cases. CONCLUSION: Using learning with limited labeling techniques, pneumothorax was identified on US with an accuracy of 80%. Several potential improvements are controlling for chest wall motion and the use of longer videos. LEVEL OF EVIDENCE: Diagnostic Tests; Level III.

Optimal transport features for morphometric population analysis.

Brain pathologies often manifest as partial or complete loss of tissue. The goal of many neuroimaging studies is to capture the location and amount of tissue changes with respect to a clinical variable of interest, such as disease progression. Morphometric analysis approaches capture local differences in the distribution of tissue or other quantities of interest in relation to a clinical variable. We propose to augment morphometric analysis with an additional feature extraction step based on unbalanced optimal transport. The optimal transport feature extraction step increases statistical power for pathologies that cause spatially dispersed tissue loss, minimizes sensitivity to shifts due to spatial misalignment or differences in brain topology, and separates changes due to volume differences from changes due to tissue location. We demonstrate the proposed optimal transport feature extraction step in the context of a volumetric morphometric analysis of the OASIS-1 study for Alzheimer's disease. The results demonstrate that the proposed approach can identify tissue changes and differences that are not otherwise measurable.

A Feature-based Affine Registration Method for Capturing Background Lung Tissue Deformation for Ground Glass Nodule Tracking.

Lung nodule tracking assessment relies on cross-sectional measurements of the largest lesion profile depicted in initial and follow-up computed tomography (CT) images. However, apparent changes in nodule size assessed via simple image-based measurements may also be compromised by the effect of the background lung tissue deformation on the GGN between the initial and follow-up images, leading to erroneous conclusions about nodule changes due to disease. To compensate for the lung deformation and enable consistent nodule tracking, here we propose a feature-based affine registration method and study its performance vis-a-vis several other registration methods. We implement and test each registration method using both a lung- and a lesion-centered region of interest on ten patient CT datasets featuring twelve nodules, including both benign and malignant GGO lesions containing pure GGNs, part-solid, or solid nodules. We evaluate each registration method according to the target registration error (TRE) computed across 30 - 50 homologous fiducial landmarks surrounding the lesions and selected by expert radiologists in both the initial and follow-up patient CT images. Our results show that the proposed feature-based affine lesion-centered registration yielded a 1.1 ± 1.2 mm TRE, while a Symmetric Normalization deformable registration yielded a 1.2 ± 1.2 mm TRE, and a least-square fit registration of the 30-50 validation fiducial landmark set yielded a 1.5 ± 1.2 mm TRE. Although the deformable registration yielded a slightly higher registration accuracy than the feature-based affine registration, it is significantly more computationally efficient, eliminates the need for ambiguous segmentation of GGNs featuring ill-defined borders, and reduces the susceptibility of artificial deformations introduced by the deformable registration, which may lead to increased similarity between the registered initial and follow-up images, over-compensating for the background lung tissue deformation, and, in turn, compromising the true disease-induced nodule change assessment. We also assessed the registration qualitatively, by visual inspection of the subtraction images, and conducted a pilot pre-clinical study that showed the proposed feature-based lesion-centered affine registration effectively compensates for the background lung tissue deformation between the initial and follow-up images and also serves as a reliable baseline registration method prior to assessing lung nodule changes due to disease.

Perfusion Imaging: An Advection Diffusion Approach.

Perfusion imaging is of great clinical importance and is used to assess a wide range of diseases including strokes and brain tumors. Commonly used approaches for the quantitative analysis of perfusion images are based on measuring the effect of a contrast agent moving through blood vessels and into tissue. Contrast-agent free approaches, for example, based on intravoxel incoherent motion and arterial spin labeling, also exist, but are so far not routinely used clinically. Existing contrast-agent-dependent methods typically rely on the estimation of the arterial input function (AIF) to approximately model tissue perfusion. These approaches neglect spatial dependencies. Further, as reliably estimating the AIF is non-trivial, different AIF estimates may lead to different perfusion measures. In this work we therefore propose PIANO, an approach that provides additional insights into the perfusion process. PIANO estimates the velocity and diffusion fields of an advection-diffusion model best explaining the contrast dynamics without using an AIF. PIANO accounts for spatial dependencies and neither requires estimating the AIF nor relies on a particular contrast agent bolus shape. Specifically, we propose a convenient parameterization of the estimation problem, a numerical estimation approach, and extensively evaluate PIANO. Simulation experiments show the robustness and effectiveness of PIANO, along with its ability to distinguish between advection and diffusion. We further apply PIANO on a public brain magnetic resonance (MR) perfusion dataset of acute stroke patients, and demonstrate that PIANO can successfully resolve velocity and diffusion field ambiguities and results in sensitive measures for the assessment of stroke, comparing favorably to conventional measures of perfusion.

Investigating training-test data splitting strategies for automated segmentation and scoring of COVID-19 lung ultrasound images.

Ultrasound in point-of-care lung assessment is becoming increasingly relevant. This is further reinforced in the context of the COVID-19 pandemic, where rapid decisions on the lung state must be made for staging and monitoring purposes. The lung structural changes due to severe COVID-19 modify the way ultrasound propagates in the parenchyma. This is reflected by changes in the appearance of the lung ultrasound images. In abnormal lungs, vertical artifacts known as B-lines appear and can evolve into white lung patterns in the more severe cases. Currently, these artifacts are assessed by trained physicians, and the diagnosis is qualitative and operator dependent. In this article, an automatic segmentation method using a convolutional neural network is proposed to automatically stage the progression of the disease. 1863 B-mode images from 203 videos obtained from 14 asymptomatic individual,14 confirmed COVID-19 cases, and 4 suspected COVID-19 cases were used. Signs of lung damage, such as the presence and extent of B-lines and white lung areas, are manually segmented and scored from zero to three (most severe). These manually scored images are considered as ground truth. Different test-training strategies are evaluated in this study. The results shed light on the efficient approaches and common challenges associated with automatic segmentation methods.

Automatic Spine Ultrasound Segmentation for Scoliosis Visualization and Measurement.

OBJECTIVE: Integrate tracked ultrasound and AI methods to provide a safer and more accessible alternative to X-ray for scoliosis measurement. We propose automatic ultrasound segmentation for 3-dimensional spine visualization and scoliosis measurement to address difficulties in using ultrasound for spine imaging. METHODS: We trained a convolutional neural network for spine segmentation on ultrasound scans using data from eight healthy adult volunteers. We tested the trained network on eight pediatric patients. We evaluated image segmentation and 3-dimensional volume reconstruction for scoliosis measurement. RESULTS: As expected, fuzzy segmentation metrics reduced when trained networks were translated from healthy volunteers to patients. Recall decreased from 0.72 to 0.64 (8.2% decrease), and precision from 0.31 to 0.27 (3.7% decrease). However, after finding optimal thresholds for prediction maps, binary segmentation metrics performed better on patient data. Recall decreased from 0.98 to 0.97 (1.6% decrease), and precision from 0.10 to 0.06 (4.5% decrease). Segmentation prediction maps were reconstructed to 3-dimensional volumes and scoliosis was measured in all patients. Measurement in these reconstructions took less than 1 minute and had a maximum error of 2.2° compared to X-ray. CONCLUSION: automatic spine segmentation makes scoliosis measurement both efficient and accurate in tracked ultrasound scans. SIGNIFICANCE: Automatic segmentation may overcome the limitations of tracked ultrasound that so far prevented its use as an alternative of X-ray in scoliosis measurement.

Patient-Specific Registration of Pre-operative and Post-recurrence Brain Tumor MRI Scans.

Registering brain magnetic resonance imaging (MRI) scans containing pathologies is challenging primarily due to large deformations caused by the pathologies, leading to missing correspondences between scans. However, the registration task is important and directly related to personalized medicine, as registering between baseline pre-operative and post-recurrence scans may allow the evaluation of tumor infiltration and recurrence. While many registration methods exist, most of them do not specifically account for pathologies. Here, we propose a framework for the registration of longitudinal image-pairs of individual patients diagnosed with glioblastoma. Specifically, we present a combined image registration/reconstruction approach, which makes use of a patient-specific principal component analysis (PCA) model of image appearance to register baseline pre-operative and post-recurrence brain tumor scans. Our approach uses the post-recurrence scan to construct a patient-specific model, which then guides the registration of the pre-operative scan. Quantitative and qualitative evaluations of our framework on 10 patient image-pairs indicate that it provides excellent registration performance without requiring (1) any human intervention or (2) prior knowledge of tumor location, growth or appearance.

Image-Based Methods for Phase Estimation, Gating, and Temporal Superresolution of Cardiac Ultrasound.

OBJECTIVE: Ultrasound is an effective tool for rapid noninvasive assessment of cardiac structure and function. Determining the cardiorespiratory phases of each frame in the ultrasound video and capturing the cardiac function at a much higher temporal resolution are essential in many applications. Fulfilling these requirements is particularly challenging in preclinical studies involving small animals with high cardiorespiratory rates, requiring cumbersome and expensive specialized hardware. METHODS: We present a novel method for the retrospective estimation of cardiorespiratory phases directly from the ultrasound videos. It transforms the videos into a univariate time series preserving the evidence of periodic cardiorespiratory motion, decouples the signatures of cardiorespiratory motion with a trend extraction technique, and estimates the cardiorespiratory phases using a Hilbert transform approach. We also present a robust nonparametric regression technique for respiratory gating and a novel kernel-regression model for reconstructing images at any cardiac phase facilitating temporal superresolution. RESULTS: We validated our methods using two-dimensional echocardiography videos and electrocardiogram (ECG) recordings of six mice. Our cardiac phase estimation method provides accurate phase estimates with a mean-phase-error range of 3%-6% against ECG derived phase and outperforms three previously published methods in locating ECGs R-wave peak frames with a mean-frame-error range of 0.73-1.36. Our kernel-regression model accurately reconstructs images at any cardiac phase with a mean-normalized-correlation range of 0.81-0.85 over 50 leave-one-out-cross-validation rounds. CONCLUSION AND SIGNIFICANCE: Our methods can enable tracking of cardiorespiratory phases without additional hardware and reconstruction of respiration-free single cardiac-cycle videos at a much higher temporal resolution.

Ultrasound Measurement of Vascular Density to Evaluate Response to Anti-Angiogenic Therapy in Renal Cell Carcinoma.

BACKGROUND: Functional and molecular changes often precede gross anatomical changes, so early assessment of a tumor's functional and molecular response to therapy can help reduce a patient's exposure to the side effects of ineffective chemotherapeutics or other treatment strategies. OBJECTIVE: Our intent was to test the hypothesis that an ultrasound microvascular imaging approach might provide indications of response to therapy prior to assessment of tumor size. METHODS: Mice bearing clear-cell renal cell carcinoma xenograft tumors were treated with antiangiogenic and Notch inhibition therapies. An ultrasound measurement of microvascular density was used to serially track the tumor response to therapy. RESULTS: Data indicated that ultrasound-derived microvascular density can indicate response to therapy a week prior to changes in tumor volume and is strongly correlated with physiological characteristics of the tumors as measured by histology ([Formula: see text]). Furthermore, data demonstrated that ultrasound measurements of vascular density can determine response to therapy and classify between-treatment groups with high sensitivity and specificity. CONCLUSION/SIGNIFICANCE: Results suggests that future applications utilizing ultrasound imaging to monitor tumor response to therapy may be able to provide earlier insight into tumor behavior from metrics of microvascular density rather than anatomical tumor size measurements.

A new preclinical ultrasound platform for widefield 3D imaging of rodents.

Noninvasive in vivo imaging technologies enable researchers and clinicians to detect the presence of disease and longitudinally study its progression. By revealing anatomical, functional, or molecular changes, imaging tools can provide a near real-time assessment of important biological events. At the preclinical research level, imaging plays an important role by allowing disease mechanisms and potential therapies to be evaluated noninvasively. Because functional and molecular changes often precede gross anatomical changes, there has been a significant amount of research exploring the ability of different imaging modalities to track these aspects of various diseases. Herein, we present a novel robotic preclinical contrast-enhanced ultrasound system and demonstrate its use in evaluating tumors in a rodent model. By leveraging recent advances in ultrasound, this system favorably compares with other modalities, as it can perform anatomical, functional, and molecular imaging and is cost-effective, portable, and high throughput, without using ionizing radiation. Furthermore, this system circumvents many of the limitations of conventional preclinical ultrasound systems, including a limited field-of-view, low throughput, and large user variability.

SCOLIOSIS SCREENING AND MONITORING USING SELF CONTAINED ULTRASOUND AND NEURAL NETWORKS.

We aim to diagnose scoliosis using a self contained ultrasound device that does not require significant training to operate. The device knows its angle relative to vertical using an embedded inertial measurement unit, and it estimates its angle relative to a vertebrae using a neural network analysis of its ultrasound images. The composition of those angles defines the angle of a vertebrae from vertical. The maximum difference between vertebrae angles collected from a scan of a spine yields the Cobb angle measure that is used to quantify scoliosis severity.

Brain extraction from normal and pathological images: A joint PCA/Image-Reconstruction approach.

Brain extraction from 3D medical images is a common pre-processing step. A variety of approaches exist, but they are frequently only designed to perform brain extraction from images without strong pathologies. Extracting the brain from images exhibiting strong pathologies, for example, the presence of a brain tumor or of a traumatic brain injury (TBI), is challenging. In such cases, tissue appearance may substantially deviate from normal tissue appearance and hence violates algorithmic assumptions for standard approaches to brain extraction; consequently, the brain may not be correctly extracted. This paper proposes a brain extraction approach which can explicitly account for pathologies by jointly modeling normal tissue appearance and pathologies. Specifically, our model uses a three-part image decomposition: (1) normal tissue appearance is captured by principal component analysis (PCA), (2) pathologies are captured via a total variation term, and (3) the skull and surrounding tissue is captured by a sparsity term. Due to its convexity, the resulting decomposition model allows for efficient optimization. Decomposition and image registration steps are alternated to allow statistical modeling of normal tissue appearance in a fixed atlas coordinate system. As a beneficial side effect, the decomposition model allows for the identification of potentially pathological areas and the reconstruction of a quasi-normal image in atlas space. We demonstrate the effectiveness of our approach on four datasets: the publicly available IBSR and LPBA40 datasets which show normal image appearance, the BRATS dataset containing images with brain tumors, and a dataset containing clinical TBI images. We compare the performance with other popular brain extraction models: ROBEX, BEaST, MASS, BET, BSE and a recently proposed deep learning approach. Our model performs better than these competing approaches on all four datasets. Specifically, our model achieves the best median (97.11) and mean (96.88) Dice scores over all datasets. The two best performing competitors, ROBEX and MASS, achieve scores of 96.23/95.62 and 96.67/94.25 respectively. Hence, our approach is an effective method for high quality brain extraction for a wide variety of images.

Exploratory Population Analysis with Unbalanced Optimal Transport.

The plethora of data from neuroimaging studies provide a rich opportunity to discover effects and generate hypotheses through exploratory data analysis. Brain pathologies often manifest in changes in shape along with deterioration and alteration of brain matter, i.e., changes in mass. We propose a morphometry approach using unbalanced optimal transport that detects and localizes changes in mass and separates them from changes due to the location of mass. The approach generates images of mass allocation and mass transport cost for each subject in the population. Voxelwise correlations with clinical variables highlight regions of mass allocation or mass transfer related to the variables. We demonstrate the method on the white and gray matter segmentations from the OASIS brain MRI data set. The separation of white and gray matter ensures that optimal transport does not transfer mass between different tissues types and separates gray and white matter related changes. The OASIS data set includes subjects ranging from healthy to mild and moderate dementia, and the results corroborate known pathology changes related to dementia that are not discovered with traditional voxel-based morphometry. The transport-based morphometry increases the explanatory power of regression on clinical variables compared to traditional voxel-based morphometry, indicating that transport cost and mass allocation images capture a larger portion of pathology induced changes.

EFFICIENT REGISTRATION OF PATHOLOGICAL IMAGES: A JOINT PCA/IMAGE-RECONSTRUCTION APPROACH.

Registration involving one or more images containing pathologies is challenging, as standard image similarity measures and spatial transforms cannot account for common changes due to pathologies. Low-rank/Sparse (LRS) decomposition removes pathologies prior to registration; however, LRS is memory-demanding and slow, which limits its use on larger data sets. Additionally, LRS blurs normal tissue regions, which may degrade registration performance. This paper proposes an efficient alternative to LRS: (1) normal tissue appearance is captured by principal component analysis (PCA) and (2) blurring is avoided by an integrated model for pathology removal and image reconstruction. Results on synthetic and BRATS 2015 data demonstrate its utility.

Automatic Estimation of the Optic Nerve Sheath Diameter from Ultrasound Images.

We present an algorithm to automatically estimate the diameter of the optic nerve sheath from ocular ultrasound images. The optic nerve sheath diameter provides a proxy for measuring intracranial pressure, a life threating condition frequently associated with head trauma. Early treatment of elevated intracranial pressures greatly improves outcomes and drastically reduces the mortality rate. We demonstrate that the proposed algorithm combined with a portable ultrasound device presents a viable path for early detection of elevated intracranial pressure in remote locations and without access to trained medical imaging experts.

Ultrasound Augmentation: Rapid 3-D Scanning for Tracking and On-Body Display.

By using a laser projector and high speed camera, we can add three capabilities to an ultrasound system: tracking the probe, tracking the patient, and projecting information onto the probe and patient. We can use these capabilities to guide an untrained operator to take high quality, well framed ultrasound images for computer-augmented, point-of-care ultrasound applications.

Increasing the impact of medical image computing using community-based open-access hackathons: The NA-MIC and 3D Slicer experience.

The National Alliance for Medical Image Computing (NA-MIC) was launched in 2004 with the goal of investigating and developing an open source software infrastructure for the extraction of information and knowledge from medical images using computational methods. Several leading research and engineering groups participated in this effort that was funded by the US National Institutes of Health through a variety of infrastructure grants. This effort transformed 3D Slicer from an internal, Boston-based, academic research software application into a professionally maintained, robust, open source platform with an international leadership and developer and user communities. Critical improvements to the widely used underlying open source libraries and tools-VTK, ITK, CMake, CDash, DCMTK-were an additional consequence of this effort. This project has contributed to close to a thousand peer-reviewed publications and a growing portfolio of US and international funded efforts expanding the use of these tools in new medical computing applications every year. In this editorial, we discuss what we believe are gaps in the way medical image computing is pursued today; how a well-executed research platform can enable discovery, innovation and reproducible science ("Open Science"); and how our quest to build such a software platform has evolved into a productive and rewarding social engineering exercise in building an open-access community with a shared vision.

Registration of Pathological Images.

This paper proposes an approach to improve atlas-to-image registration accuracy with large pathologies. Instead of directly registering an atlas to a pathological image, the method learns a mapping from the pathological image to a quasi-normal image, for which more accurate registration is possible. Specifically, the method uses a deep variational convolutional encoder-decoder network to learn the mapping. Furthermore, the method estimates local mapping uncertainty through network inference statistics and uses those estimates to down-weight the image registration similarity measure in areas of high uncertainty. The performance of the method is quantified using synthetic brain tumor images and images from the brain tumor segmentation challenge (BRATS 2015).