This PDF file contains the editorial “In Memoriam: Lee Rosen” for JMI Vol. 3 Issue 02

Retinal image analysis is emerging as a key source of biomarkers of chronic systemic conditions affecting the cardiovascular system and brain. The rapid development and increasing diversity of commercial retinal imaging systems present a challenge to image analysis software providers. In addition, clinicians are looking to extract maximum value from the clinical imaging taking place. We describe how existing and well-established retinal vasculature segmentation and measurement software for fundus camera images has been modulated to analyze scanning laser ophthalmoscope retinal images generated by the dual-modality Heidelberg SPECTRALIS^® instrument, which also features optical coherence tomography.

A diffusion weighted imaging (DWI) approach that is signal-to-noise ratio (SNR) efficient and can be applied to achieve sub-mm resolutions on clinical 3 T systems was developed. The sequence combined a multislab, multishot pulsed gradient spin echo diffusion scheme with spiral readouts for imaging data and navigators. Long data readouts were used to keep the number of shots, and hence total imaging time, for the three-dimensional acquisition short. Image quality was maintained by incorporating a field-inhomogeneity-corrected image reconstruction to remove distortions associated with long data readouts. Additionally, multiple shots were required for the high-resolution images, necessitating motion induced phase correction through the use of efficiently integrated navigator data. The proposed approach is compared with two-dimensional (2-D) acquisitions that use either a spiral or a typical echo-planar imaging (EPI) acquisition to demonstrate the improved SNR efficiency. The proposed technique provided 71% higher SNR efficiency than the standard 2-D EPI approach. The adaptability of the technique to achieve high spatial resolutions is demonstrated by acquiring diffusion tensor imaging data sets with isotropic resolutions of 1.25 and 0.8 mm. The proposed approach allows for SNR-efficient sub-mm acquisitions of DWI data on clinical 3 T systems.

The therapy operating characteristic (TOC) curve, developed in the context of radiation therapy, is a plot of the probability of tumor control versus the probability of normal-tissue complications as the overall radiation dose level is varied, e.g., by varying the beam current in external-beam radiotherapy or the total injected activity in radionuclide therapy. This paper shows how TOC can be applied to chemotherapy with the administered drug dosage as the variable. The area under a TOC curve (AUTOC) can be used as a figure of merit for therapeutic efficacy, analogous to the area under an ROC curve (AUROC), which is a figure of merit for diagnostic efficacy. In radiation therapy, AUTOC can be computed for a single patient by using image data along with radiobiological models for tumor response and adverse side effects. The mathematical analogy between response of observers to images and the response of tumors to distributions of a chemotherapy drug is exploited to obtain linear discriminant functions from which AUTOC can be calculated. Methods for using mathematical models of drug delivery and tumor response with imaging data to estimate patient-specific parameters that are needed for calculation of AUTOC are outlined. The implications of this viewpoint for clinical trials are discussed.

A semi-analytical model describing spectral distortions in photon-counting detectors (PCDs) for clinical computed tomography was evaluated using simulated data. The distortions were due to count rate-independent spectral response effects and count rate-dependent pulse-pileup effects and the model predicted both the mean count rates and the spectral shape. The model parameters were calculated using calibration data. The model was evaluated by comparing the predicted x-ray spectra to Monte Carlo simulations of a PCD at various count rates. The data-model agreement expressed as weighted coefficient of variation (COV_W) was better than COV_W=2.0% for dead time losses up to 28% and COV_W=20% or smaller for dead time losses up to 69%. The accuracy of the model was also tested for the purpose of material decomposition by estimating material thicknesses from simulated projection data. The estimated attenuator thicknesses generally agreed with the true values within one standard deviation of the statistical uncertainty obtained from multiple noise realizations.

Channelized Hotelling observer (CHO) models have been shown to correlate well with human observers for several phantom-based detection/classification tasks in clinical computed tomography (CT). A large number of repeated scans were used to achieve an accurate estimate of the model’s template. The purpose of this study is to investigate how the experimental and CHO model parameters affect the minimum required number of repeated scans. A phantom containing 21 low-contrast objects was scanned on a 128-slice CT scanner at three dose levels. Each scan was repeated 100 times. For each experimental configuration, the low-contrast detectability, quantified as the area under receiver operating characteristic curve, A_z, was calculated using a previously validated CHO with randomly selected subsets of scans, ranging from 10 to 100. Using A_z from the 100 scans as the reference, the accuracy from a smaller number of scans was determined. Our results demonstrated that the minimum number of repeated scans increased when the radiation dose level decreased, object size and contrast level decreased, and the number of channels increased. As a general trend, it increased as the low-contrast detectability decreased. This study provides a basis for the experimental design of task-based image quality assessment in clinical CT using CHO.

Energy-discriminating, photon-counting (EDPC) detectors are attractive for their potential for improved detective quantum efficiency and for their spectral imaging capabilities. However, at high count rates, counts are lost, the detected spectrum is distorted, and the advantages of EDPC detectors disappear. Existing EDPC detectors identify counts by analyzing the signal with a bank of comparators. We explored alternative methods for pulse detection for multibin EDPC detectors that could improve performance at high count rates. The detector signal was simulated in a Monte Carlo fashion assuming a bipolar shape and analyzed using several methods, including the conventional bank of comparators. For example, one method recorded the peak energy of the pulse along with the width (temporal extent) of the pulse. The Cramer–Rao lower bound of the variance of basis material estimates was numerically found for each method. At high count rates, the variance in water material (bone canceled) measurements could be reduced by as much as an order of magnitude. Improvements in virtual monoenergetic images were modest. We conclude that stochastic noise in spectral imaging tasks could be reduced if alternative methods for pulse detection were utilized.

Cardiac computed tomography (CT) acquisitions for perfusion assessment can be performed in a dynamic or static mode. Either method may be used for a variety of clinical tasks, including (1) stratifying patients into categories of ischemia and (2) using a quantitative myocardial blood flow (MBF) estimate to evaluate disease severity. In this simulation study, we compare method performance on these classification and quantification tasks for matched radiation dose levels and for different flow states, patient sizes, and injected contrast levels. Under conditions simulated, the dynamic method has low bias in MBF estimates (0 to 0.1  ml/min/g) compared to linearly interpreted static assessment (0.45 to 0.48  ml/min/g), making it more suitable for quantitative estimation. At matched radiation dose levels, receiver operating characteristic analysis demonstrated that the static method, with its high bias but generally lower variance, had superior performance (p<0.05) in stratifying patients, especially for larger patients and lower contrast doses [area under the curve (AUC)=0.95 to 96 versus 0.86]. We also demonstrate that static assessment with a correctly tuned exponential relationship between the apparent CT number and MBF has superior quantification performance to static assessment with a linear relationship and to dynamic assessment. However, tuning the exponential relationship to the patient and scan characteristics will likely prove challenging. This study demonstrates that the selection and optimization of static or dynamic acquisition modes should depend on the specific clinical task.

Respiratory motion is a significant obstacle to the use of quantitative perfusion in clinical practice. Increasingly complex motion correction algorithms are being developed to correct for respiratory motion. However, the impact of these improvements on the final diagnosis of ischemic heart disease has not been evaluated. The aim of this study was to compare the performance of four automated correction methods in terms of their impact on diagnostic accuracy. Three strategies for motion correction were used: (1) independent translation correction for all slices, (2) translation correction for the basal slice with transform propagation to the remaining two slices assuming identical motion in the remaining slices, and (3) rigid correction (translation and rotation) for the basal slice. There were no significant differences in diagnostic accuracy between the manual and automatic motion-corrected datasets (p=0.88). The area under the curve values for manual motion correction and automatic motion correction were 0.93 and 0.92, respectively. All of the automated motion correction methods achieved a comparable diagnostic accuracy to manual correction. This suggests that the simplest automated motion correction method (method 2 with translation transform for basal location and transform propagation to the remaining slices) is a sufficiently complex motion correction method for use in quantitative myocardial perfusion.

Interactive segmentation is becoming of increasing interest to the medical imaging community in that it combines the positive aspects of both manual and automated segmentation. However, general-purpose tools have been lacking in terms of segmenting multiple regions simultaneously with a high degree of coupling between groups of labels. Hierarchical max-flow segmentation has taken advantage of this coupling for individual applications, but until recently, these algorithms were constrained to a particular hierarchy and could not be considered general-purpose. In a generalized form, the hierarchy for any given segmentation problem is specified in run-time, allowing different hierarchies to be quickly explored. We present an interactive segmentation interface, which uses generalized hierarchical max-flow for optimization-based multiregion segmentation guided by user-defined seeds. Applications in cardiac and neonatal brain segmentation are given as example applications of its generality.

Among all types of cancer, gynecological malignancies belong to the fourth most frequent type of cancer among women. In addition to chemotherapy and external beam radiation, brachytherapy is the standard procedure for the treatment of these malignancies. In the progress of treatment planning, localization of the tumor as the target volume and adjacent organs of risks by segmentation is crucial to accomplish an optimal radiation distribution to the tumor while simultaneously preserving healthy tissue. Segmentation is performed manually and represents a time-consuming task in clinical daily routine. This study focuses on the segmentation of the rectum/sigmoid colon as an organ-at-risk in gynecological brachytherapy. The proposed segmentation method uses an interactive, graph-based segmentation scheme with a user-defined template. The scheme creates a directed two-dimensional graph, followed by the minimal cost closed set computation on the graph, resulting in an outlining of the rectum. The graph’s outline is dynamically adapted to the last calculated cut. Evaluation was performed by comparing manual segmentations of the rectum/sigmoid colon to results achieved with the proposed method. The comparison of the algorithmic to manual result yielded a dice similarity coefficient value of 83.85±4.08, in comparison to 83.97±8.08% for the comparison of two manual segmentations by the same physician. Utilizing the proposed methodology resulted in a median time of 128  s/dataset, compared to 300 s needed for pure manual segmentation.

Analysis of intravascular optical coherence tomography (IVOCT) data has potential for real-time in vivo plaque classification. We developed a processing pipeline on a three-dimensional local region of support for estimation of optical properties of atherosclerotic plaques from coronary artery, IVOCT pullbacks. Using realistic coronary artery disease phantoms, we determined insignificant differences in mean and standard deviation estimates between our pullback analyses and more conventional processing of stationary acquisitions with frame averaging. There was no effect of tissue depth or oblique imaging on pullback parameter estimates. The method’s performance was assessed in comparison with observer-defined standards using clinical pullback data. Values (calcium 3.58±1.74  mm−¹, lipid 9.93±2.44  mm−¹, and fibrous 1.96±1.11  mm−¹) were consistent with previous measurements obtained by other means. Using optical parameters (μ_t, 〈I〉, I₀), we achieved feature space separation of plaque types and classification accuracy of 92.5±3%. Despite the rapid z motion and varying incidence angle in pullbacks, the proposed computational pipeline appears to work as well as a more standard “stationary” approach.

Qualitative screening for colorectal polyps via fiber bundle microendoscopy imaging has shown promising results, with studies reporting high rates of sensitivity and specificity, as well as low interobserver variability with trained clinicians. A quantitative image quality control and image feature extraction algorithm (QFEA) was designed to lessen the burden of training and provide objective data for improved clinical efficacy of this method. After a quantitative image quality control step, QFEA extracts field-of-view area, crypt area, crypt circularity, and crypt number per image. To develop and validate this QFEA, a training set of microendoscopy images was collected from freshly resected porcine colon epithelium. The algorithm was then further validated on ex vivo image data collected from eight human subjects, selected from clinically normal appearing regions distant from grossly visible tumor in surgically resected colorectal tissue. QFEA has proven flexible in application to both mosaics and individual images, and its automated crypt detection sensitivity ranges from 71 to 94% despite intensity and contrast variation within the field of view. It also demonstrates the ability to detect and quantify differences in grossly normal regions among different subjects, suggesting the potential efficacy of this approach in detecting occult regions of dysplasia.

Volumetric medical images of a single subject can be acquired using different imaging modalities, such as computed tomography, magnetic resonance imaging (MRI), and positron emission tomography. In this work, we present a semiautomatic segmentation algorithm that can leverage the synergies between different image modalities while integrating interactive human guidance. The algorithm provides a statistical segmentation framework partly automating the segmentation task while still maintaining critical human oversight. The statistical models presented are trained interactively using simple brush strokes to indicate tumor and nontumor tissues and using intermediate results within a patient’s image study. To accomplish the segmentation, we construct the energy function in the conditional random field (CRF) framework. For each slice, the energy function is set using the estimated probabilities from both user brush stroke data and prior approved segmented slices within a patient study. The progressive segmentation is obtained using a graph-cut-based minimization. Although no similar semiautomated algorithm is currently available, we evaluated our method with an MRI data set from Medical Image Computing and Computer Assisted Intervention Society multimodal brain segmentation challenge (BRATS 2012 and 2013) against a similar fully automatic method based on CRF and a semiautomatic method based on grow-cut, and our method shows superior performance.

Deep brain stimulation of the medial globus pallidus (GPm) is a surgical procedure for treating patients suffering from Parkinson’s disease. Its therapeutic effect may be limited by the presence of pyramidal tract side effect (PTSE). PTSE is a contraction time-locked to the stimulation when the current spreading reaches the motor fibers of the pyramidal tract within the internal capsule. The objective of the study was to propose a preoperative predictive model of PTSE. A machine learning-based method called PyMAN (PTSE model based on artificial neural network) accounting for the current used in stimulation, the three-dimensional electrode coordinates and the angle of the trajectory, was designed to predict the occurrence of PTSE. Ten patients implanted in the GPm have been tested by a clinician to create a labeled dataset of the stimulation parameters that trigger PTSE. The kappa index value between the data predicted by PyMAN and the labeled data was 0.78. Further evaluation studies are desirable to confirm whether PyMAN could be a reliable tool for assisting the surgeon to prevent PTSE during the preoperative planning.

Stereoscopic medical videos are recorded, e.g., in stereo endoscopy or during video recording medical/dental operations. This paper examines quality issues in the recorded stereoscopic medical videos, as insufficient quality may induce visual fatigue to doctors. No attention has been paid to stereo quality and ensuing fatigue issues in the scientific literature so far. Two of the most commonly encountered quality issues in stereoscopic data, namely stereoscopic window violations and bent windows, were searched for in stereo endoscopic medical videos. Furthermore, an additional stereo quality issue encountered in dental operation videos, namely excessive disparity, was detected and fixed. The conducted experiments prove the existence of such quality issues in stereoscopic medical data and highlight the need for their detection and correction.

Fetal motion manifests as signal degradation and image artifact in the acquired time series of blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) studies. We present a robust preprocessing pipeline to specifically address fetal and placental motion-induced artifacts in stimulus-based fMRI with slowly cycled block design in the living fetus. In the proposed pipeline, motion correction is optimized to the experimental paradigm, and it is performed separately in each phase as well as in each region of interest (ROI), recognizing that each phase and organ experiences different types of motion. To obtain the averaged BOLD signals for each ROI, both misaligned volumes and noisy voxels are automatically detected and excluded, and the missing data are then imputed by statistical estimation based on local polynomial smoothing. Our experimental results demonstrate that the proposed pipeline was effective in mitigating the motion-induced artifacts in stimulus-based fMRI data of the fetal brain and placenta.

Quantitative fat-water MRI (FWMRI) methods provide valuable information about the distribution, volume, and composition of adipose tissue (AT). Ultra high field FWMRI of animal models may have the potential to provide insights into the progression of obesity and its comorbidities. Here, we present quantitative FWMRI with all known confounder corrections on a 15.2T preclinical scanner for noninvasive in vivo monitoring of an established diet-induced obesity mouse model. Male C57BL/6J mice were placed on a low-fat (LFD) or a high-fat diet (HFD). Three-dimensional (3-D) multiple gradient echo MRI at 15.2T was performed at baseline, 4, 8, 12, and 16 weeks after diet onset. A 3-D fat-water separation algorithm and additional processing were used to generate proton-density fat fraction (PDFF), local magnetic field offset, and R*₂ maps. We examined these parameters in perirenal AT ROIs from LFD and HFD mice. The data suggest that PDFF, local field offset, and R*₂ have different time course behaviors between LFD and HFD mice over 16 weeks. This work suggests FWMRI at 15.2T may be a useful tool for longitudinal studies of adiposity due to the advantages of ultra high field although further investigation is needed to understand the observed time course behavior.

Although computed tomography (CT) perfusion (CTP) imaging enables rapid diagnosis and prognosis of ischemic stroke, current CTP analysis methods have several shortcomings. We propose a fast nonlinear regression method with a box-shaped model (boxNLR) that has important advantages over the current state-of-the-art method, block-circulant singular value decomposition (bSVD). These advantages include improved robustness to attenuation curve truncation, extensibility, and unified estimation of perfusion parameters. The method is compared with bSVD and with a commercial SVD-based method. The three methods were quantitatively evaluated by means of a digital perfusion phantom, described by Kudo et al. and qualitatively with the aid of 50 clinical CTP scans. All three methods yielded high Pearson correlation coefficients (<0.9) with the ground truth in the phantom. The boxNLR perfusion maps of the clinical scans showed higher correlation with bSVD than the perfusion maps from the commercial method. Furthermore, it was shown that boxNLR estimates are robust to noise, truncation, and tracer delay. The proposed method provides a fast and reliable way of estimating perfusion parameters from CTP scans. This suggests it could be a viable alternative to current commercial and academic methods.

Evidence suggests high-resolution, high-contrast, 100  frames/s intravascular optical coherence tomography (IVOCT) can distinguish plaque types, but further validation is needed, especially for automated plaque characterization. We developed experimental and three-dimensional (3-D) registration methods to provide validation of IVOCT pullback volumes using microscopic, color, and fluorescent cryo-image volumes with optional registered cryo-histology. A specialized registration method matched IVOCT pullback images acquired in the catheter reference frame to a true 3-D cryo-image volume. Briefly, an 11-parameter registration model including a polynomial virtual catheter was initialized within the cryo-image volume, and perpendicular images were extracted, mimicking IVOCT image acquisition. Virtual catheter parameters were optimized to maximize cryo and IVOCT lumen overlap. Multiple assessments suggested that the registration error was better than the 200-μm spacing between IVOCT image frames. Tests on a digital synthetic phantom gave a registration error of only +1.3±2.7  μm (signed distance). Visual assessment of randomly presented nearby frames suggested registration accuracy within 1 IVOCT frame interval (−25.0±174.3  μm). This would eliminate potential misinterpretations confronted by the typical histological approaches to validation, with estimated 1-mm errors. The method can be used to create annotated datasets and automated plaque classification methods and can be extended to other intravascular imaging modalities.

The evolution of cloud computing is driving the next generation of medical imaging systems. However, privacy and security concerns have been consistently regarded as the major obstacles for adoption of cloud computing by healthcare domains. OpenID Connect, combining OpenID and OAuth together, is an emerging representational state transfer-based federated identity solution. It is one of the most adopted open standards to potentially become the de facto standard for securing cloud computing and mobile applications, which is also regarded as “Kerberos of cloud.” We introduce OpenID Connect as an authentication and authorization service in cloud-based diagnostic imaging (DI) systems, and propose enhancements that allow for incorporating this technology within distributed enterprise environments. The objective of this study is to offer solutions for secure sharing of medical images among diagnostic imaging repository (DI-r) and heterogeneous picture archiving and communication systems (PACS) as well as Web-based and mobile clients in the cloud ecosystem. The main objective is to use OpenID Connect open-source single sign-on and authorization service and in a user-centric manner, while deploying DI-r and PACS to private or community clouds should provide equivalent security levels to traditional computing model.

Ultrasonography is a widely used imaging modality to visualize anatomical structures due to its low cost and ease of use; however, it is challenging to acquire acceptable image quality in deep tissue. Synthetic aperture (SA) is a technique used to increase image resolution by synthesizing information from multiple subapertures, but the resolution improvement is limited by the physical size of the array transducer. With a large F-number, it is difficult to achieve high resolution in deep regions without extending the effective aperture size. We propose a method to extend the available aperture size for SA—called synthetic tracked aperture ultrasound (STRATUS) imaging—by sweeping an ultrasound transducer while tracking its orientation and location. Tracking information of the ultrasound probe is used to synthesize the signals received at different positions. Considering the practical implementation, we estimated the effect of tracking and ultrasound calibration error to the quality of the final beamformed image through simulation. In addition, to experimentally validate this approach, a 6 degree-of-freedom robot arm was used as a mechanical tracker to hold an ultrasound transducer and to apply in-plane lateral translational motion. Results indicate that STRATUS imaging with robotic tracking has the potential to improve ultrasound image quality.

Automated three-dimensional breast ultrasound (ABUS) is a valuable adjunct to x-ray mammography for breast cancer screening of women with dense breasts. High image quality is essential for proper diagnostics and computer-aided detection. We propose an automated image quality assessment system for ABUS images that detects artifacts at the time of acquisition. Therefore, we study three aspects that can corrupt ABUS images: the nipple position relative to the rest of the breast, the shadow caused by the nipple, and the shape of the breast contour on the image. Image processing and machine learning algorithms are combined to detect these artifacts based on 368 clinical ABUS images that have been rated manually by two experienced clinicians. At a specificity of 0.99, 55% of the images that were rated as low quality are detected by the proposed algorithms. The areas under the ROC curves of the single classifiers are 0.99 for the nipple position, 0.84 for the nipple shadow, and 0.89 for the breast contour shape. The proposed algorithms work fast and reliably, which makes them adequate for online evaluation of image quality during acquisition. The presented concept may be extended to further image modalities and quality aspects.

Many pulse-echo imaging systems use focused beams to improve lateral resolution. The beam width is determined by the choice of source and apodization function, the frequency, and the physics of focusing. Postprocessing strategies to improve lateral resolution can be limited by the need for conditioning the mathematics of inverse filtering, due to instabilities. We present an analysis that defines key constraints on sampled versions of lateral beampatterns. Within these constraints are useful symmetric beampatterns, which, when properly sampled, can have a stable inverse filter. A framework for analysis and processing is described and applied to phantoms and tissues to demonstrate the improvements that can be realized.

Invasive ductal breast carcinomas (IDBCs) are the most frequent and aggressive subtypes of breast cancer, affecting a large number of Canadian women every year. Part of the diagnostic process includes grading the cancerous tissue at the microscopic level according to the Nottingham modification of the Scarff-Bloom-Richardson system. Although reliable, there exists a growing interest in automating the grading process, which will provide consistent care for all patients. This paper presents a solution for automatically detecting regions expressing IDBC in images of microscopic tissue, or whole digital slides. This represents the first stage in a larger solution designed to automatically grade IDBC. The detector first tessellated whole digital slides, and image features were extracted, such as color information, local binary patterns, and histograms of oriented gradients. These were presented to a random forest classifier, which was trained and tested using a database of 66 cases diagnosed with IDBC. When properly tuned, the detector balanced accuracy, F1 score, and Dice’s similarity coefficient were 88.7%, 79.5%, and 0.69, respectively. Overall, the results seemed strong enough to integrate our detector into a larger solution equipped with components that analyze the cancerous tissue at higher magnification, automatically producing the histopathological grade.

This paper proposes a digital image analysis method to support quantitative pathology by automatically segmenting the hepatocyte structure and quantifying its morphological features. To structurally analyze histopathological hepatic images, we isolate the trabeculae by extracting the sinusoids, fat droplets, and stromata. We then measure the morphological features of the extracted trabeculae, divide the image into cords, and calculate the feature values of the local cords. We propose a method of calculating the nuclear–cytoplasmic ratio, nuclear density, and number of layers using the local cords. Furthermore, we evaluate the effectiveness of the proposed method using surgical specimens. The proposed method was found to be an effective method for the quantification of the Edmondson grade.

This PDF file contains the errata for “JMI Vol. 3 Issue 02 Paper JMI-2016-0509-ERR” for JMI Vol. 3 Issue 02