Current research in the field of positron emission tomography (PET) focuses on improving the sensitivity of the scanner with thicker detectors, extended axial field-of-view, and time-of-flight (TOF) capability. These create the need for depth-of-interaction (DOI) encoding to correct parallax errors. We have proposed a method to encode DOI using phosphor-coated crystals. Our initial work using photomultiplier tubes (PMTs) demonstrated the possibilities of the proposed method, however, a major limitation of PMTs for this application is poor quantum efficiency in yellow light, corresponding to the wavelengths of the converted light by the phosphor coating. In contrast, the red-green-blue-high-density (RGB-HD) silicon photomultipliers (SiPMs) have a high photon detection efficiency across the visible spectrum. Excellent coincidence resolving time (CRT; <210  ps) was obtained by coupling RGB-HD SiPMs and  3 × 3 × 20  mm³ lutetium fine silicate crystals coated on a third of one of their lateral sides. Events were classified in three DOI bins (∼6.7-mm width) with an average sensitivity of 83.1%. A CRT of ∼200  ps combined with robust DOI encoding is a marked improvement in the phosphor-coated approach that we pioneered. For the first time, we read out these crystals with SiPMs and clearly demonstrated the potential of the RGB-HD SiPMs for this TOF-DOI PET detector.

The overall goal of this work is to develop a rapid, accurate, and automated software tool to estimate patient-specific organ doses from computed tomography (CT) scans using simulations to generate dose maps combined with automated segmentation algorithms. This work quantified the accuracy of organ dose estimates obtained by an automated segmentation algorithm. We hypothesized that the autosegmentation algorithm is sufficiently accurate to provide organ dose estimates, since small errors delineating organ boundaries will have minimal effect when computing mean organ dose. A leave-one-out validation study of the automated algorithm was performed with 20 head-neck CT scans expertly segmented into nine regions. Mean organ doses of the automatically and expertly segmented regions were computed from Monte Carlo-generated dose maps and compared. The automated segmentation algorithm estimated the mean organ dose to be within 10% of the expert segmentation for regions other than the spinal canal, with the median error for each organ region below 2%. In the spinal canal region, the median error was −7%, with a maximum absolute error of 28% for the single-atlas approach and 11% for the multiatlas approach. The results demonstrate that the automated segmentation algorithm can provide accurate organ dose estimates despite some segmentation errors.

Photon counting detector (PCD)-based computed tomography (CT) is an emerging imaging technique. Compared to conventional energy integrating detector (EID)-based CT, PCD-CT is able to exclude electronic noise that may severely impair image quality at low photon counts. This work focused on comparing the noise performance at low doses between the PCD and EID subsystems of a whole-body research PCD-CT scanner, both qualitatively and quantitatively. An anthropomorphic thorax phantom was scanned, and images of the shoulder portion were reconstructed. The images were visually and quantitatively compared between the two subsystems in terms of streak artifacts, an indicator of the impact of electronic noise. Furthermore, a torso-shaped water phantom was scanned using a range of tube currents. The product of the noise and the square root of the tube current was calculated, normalized, and compared between the EID and PCD subsystems. Visual assessment of the thorax phantom showed that electronic noise had a noticeably stronger degrading impact in the EID images than in the PCD images. The quantitative results indicated that in low-dose situations, electronic noise had a noticeable impact (up to a 5.8% increase in magnitude relative to quantum noise) on the EID images, but negligible impact on the PCD images.

An ultrahigh-resolution (UHR) data collection mode was enabled on a whole-body, research photon counting detector (PCD) computed tomography system. In this mode, 64 rows of 0.45  mm×0.45  mm detector pixels were used, which corresponded to a pixel size of 0.25  mm×0.25  mm at the isocenter. Spatial resolution and image noise were quantitatively assessed for the UHR PCD scan mode, as well as for a commercially available UHR scan mode that uses an energy-integrating detector (EID) and a set of comb filters to decrease the effective detector size. Images of an anthropomorphic lung phantom, cadaveric swine lung, swine heart specimen, and cadaveric human temporal bone were qualitatively assessed. Nearly equivalent spatial resolution was demonstrated by the modulation transfer function measurements: 15.3 and 20.3  lp/cm spatial frequencies were achieved at 10% and 2% modulation, respectively, for the PCD system and 14.2 and 18.6  lp/cm for the EID system. Noise was 29% lower in the PCD UHR images compared to the EID UHR images, representing a potential dose savings of 50% for equivalent image noise. PCD UHR images from the anthropomorphic phantom and cadaveric specimens showed clear delineation of small structures.

Lumen segmentation from clinical intravascular optical coherence tomography (IV-OCT) images has clinical relevance as it provides a full three-dimensional perspective of diseased coronary artery sections. Inaccurate segmentation may occur when there are artifacts in the image, resulting from issues such as inadequate blood clearance. This study proposes a transmittance-based lumen intensity enhancement method that ensures only lumen regions are highlighted. A level-set-based active contour method that utilizes the local speckle distribution properties of the image is then employed to drive an image-specific active contour toward the true lumen boundaries. By utilizing local speckle properties, the intensity variation issues within the image are resolved. This combined approach has been successfully applied to challenging clinical IV-OCT datasets that contains multiple lumens, residual blood flow, and its shadowing artifact. A method to identify the guide-wire and interpolate the lost lumen segments has been implemented. This approach is fast and can be performed even when guide-wire boundaries are not easily identified. Lumen enhancement also makes it easy to identify vessel side branches. This automated approach is not only able to extract the arterial lumen, but also the smaller microvascular lumens that are associated with the vasa vasorum and with atherosclerotic plaque.

Preoperative three-dimensional (3-D) visualization of brain vasculature by digital subtraction angiography from computerized tomography (CT) in neurosurgery is gaining more and more importance, since vessels are the primary landmarks both for organs at risk and for navigation. Surgical embolization of cerebral aneurysms and arteriovenous malformations, epilepsy surgery, and stereoelectroencephalography are a few examples. Contrast-enhanced cone-beam computed tomography (CE-CBCT) represents a powerful facility, since it is capable of acquiring images in the operation room, shortly before surgery. However, standard 3-D reconstructions do not provide a direct distinction between arteries and veins, which is of utmost importance and is left to the surgeon’s inference so far. Pioneering attempts by true four-dimensional (4-D) CT perfusion scans were already described, though at the expense of longer acquisition protocols, higher dosages, and sensible resolution losses. Hence, space is open to approaches attempting to recover the contrast dynamics from standard CE-CBCT, on the basis of anomalies overlooked in the standard 3-D approach. This paper aims at presenting algebraic reconstruction technique (ART) 3.5D, a method that overcomes the clinical limitations of 4-D CT, from standard 3-D CE-CBCT scans. The strategy works on the 3-D angiography, previously segmented in the standard way, and reprocesses the dynamics hidden in the raw data to recover an approximate dynamics in each segmented voxel. Next, a classification algorithm labels the angiographic voxels and artery or vein. Numerical simulations were performed on a digital phantom of a simplified 3-D vasculature with contrast transit. CE-CBCT projections were simulated and used for ART 3.5D testing. We achieved up to 90% classification accuracy in simulations, proving the feasibility of the presented approach for dynamic information recovery for arteries and veins segmentation.

Accurate extraction of structural changes in the blood vessels of the retina is an essential task in diagnosis of retinopathy. Matched filter (MF) technique is the effective way to extract blood vessels, but the effectiveness is reduced due to noisy images. The concept of MF and MF with first-order derivative of Gaussian (MF-FDOG) has been implemented for retina images of the DRIVE database. The optimized particle swarm optimization (PSO) algorithm is used for enhancing the images by edgels to improve the performance of filters. The vessels were detected by the response of thresholding to the MF, whereas the threshold is adjusted in response to the FDOG. The PSO-based enhanced MF response significantly improved the performances of filters to extract fine blood vessels structures. Experimental results show that the proposed method based on enhanced images improved the accuracy to 91.1%, which is higher than that of MF and MF-FDOG, respectively. The peak signal-to-noise ratio was also found to be higher with low mean square error values in enhanced MF response. The accuracy, sensitivity, and specificity values are significantly improved among MF, MF-FDOG, and PSO-enhanced images (P<0.05).

Actinic cheilitis (AC) is a disease caused by prolonged and cumulative sun exposure that mostly affects the lower lip, which can progress to a lip squamous cell carcinoma. Routine diagnosis relies on clinician experience and training. We investigated the diagnostic efficacy of wide-field fluorescence imaging coupled to an automated algorithm for AC recognition. Fluorescence images were acquired from 57 patients with confirmed AC and 46 normal volunteers. Three different algorithms were employed: two based on the emission characteristics of local heterogeneity, entropy and intensity range, and one based on the number of objects after K-mean clustering. A classification model was obtained using a fivefold cross correlation algorithm. Sensitivity and specificity rates were 86% and 89.1%, respectively.

Optimization-based segmentation approaches deriving from discrete graph-cuts and continuous max-flow have become increasingly nuanced, allowing for topological and geometric constraints on the resulting segmentation while retaining global optimality. However, these two considerations, topological and geometric, have yet to be combined in a unified manner. The concept of “shape complexes,” which combine geodesic star convexity with extendable continuous max-flow solvers, is presented. These shape complexes allow more complicated shapes to be created through the use of multiple labels and super-labels, with geodesic star convexity governed by a topological ordering. These problems can be optimized using extendable continuous max-flow solvers. Previous approaches required computationally expensive coordinate system warping, which are ill-defined and ambiguous in the general case. These shape complexes are demonstrated in a set of synthetic images as well as vessel segmentation in ultrasound, valve segmentation in ultrasound, and atrial wall segmentation from contrast-enhanced CT. Shape complexes represent an extendable tool alongside other continuous max-flow methods that may be suitable for a wide range of medical image segmentation problems.

Cancer is the second leading cause of death in US after cardiovascular disease. Image-based computer-aided diagnosis can assist physicians to efficiently diagnose cancers in early stages. Existing computer-aided algorithms use hand-crafted features such as wavelet coefficients, co-occurrence matrix features, and recently, histogram of shearlet coefficients for classification of cancerous tissues and cells in images. These hand-crafted features often lack generalizability since every cancerous tissue and cell has a specific texture, structure, and shape. An alternative approach is to use convolutional neural networks (CNNs) to learn the most appropriate feature abstractions directly from the data and handle the limitations of hand-crafted features. A framework for breast cancer detection and prostate Gleason grading using CNN trained on images along with the magnitude and phase of shearlet coefficients is presented. Particularly, we apply shearlet transform on images and extract the magnitude and phase of shearlet coefficients. Then we feed shearlet features along with the original images to our CNN consisting of multiple layers of convolution, max pooling, and fully connected layers. Our experiments show that using the magnitude and phase of shearlet coefficients as extra information to the network can improve the accuracy of detection and generalize better compared to the state-of-the-art methods that rely on hand-crafted features. This study expands the application of deep neural networks into the field of medical image analysis, which is a difficult domain considering the limited medical data available for such analysis.

Computerized methods promise quick, objective, and sensitive tools to quantify progression of radiological damage in rheumatoid arthritis (RA). Measurement of joint space width (JSW) in finger and wrist joints with these systems performed comparable to the Sharp–van der Heijde score (SHS). A next step toward clinical use, validation of precision and accuracy in hand joints with minimal damage, is described with a close scrutiny of sources of error. A recently developed system to measure metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints was validated in consecutive hand images of RA patients. To assess the impact of image acquisition, measurements on radiographs from a multicenter trial and from a recent prospective cohort in a single hospital were compared. Precision of the system was tested by comparing the joint space in mm in pairs of subsequent images with a short interval without progression of SHS. In case of incorrect measurements, the source of error was analyzed with a review by human experts. Accuracy was assessed by comparison with reported measurements with other systems. In the two series of radiographs, the system could automatically locate and measure 1003/1088 (92.2%) and 1143/1200 (95.3%) individual joints, respectively. In joints with a normal SHS, the average (SD) size of MCP joints was 1.7±0.2 and 1.6±0.3  mm in the two series of radiographs, and of PIP joints 1.0±0.2 and 0.9±0.2  mm. The difference in JSW between two serial radiographs with an interval of 6 to 12 months and unchanged SHS was 0.0±0.1  mm, indicating very good precision. Errors occurred more often in radiographs from the multicenter cohort than in a more recent series from a single hospital. Detailed analysis of the 55/1125 (4.9%) measurements that had a discrepant paired measurement revealed that variation in the process of image acquisition (exposure in 15% and repositioning in 57%) was a more frequent source of error than incorrect delineation by the software (25%). Various steps in the validation of an automated measurement system for JSW of MCP and PIP joints are described. The use of serial radiographs from different sources, with a short interval and limited damage, is helpful to detect sources of error. Image acquisition, in particular repositioning, is a dominant source of error.

The segmentation of bone surfaces from magnetic resonance imaging (MRI) data has applications in the quantitative measurement of knee osteoarthritis, surgery planning for patient-specific total knee arthroplasty, and its subsequent fabrication of artificial implants. However, due to the problems associated with MRI imaging, such as low contrast between bone and surrounding tissues, noise, bias fields, and the partial volume effect, segmentation of bone surfaces continues to be a challenging operation. A framework is presented for the enhancement of knee MRI scans prior to segmentation in order to obtain high contrast bone images. During the first stage, a contrast enhanced relative total variation regularization method is used in order to remove textural noise from the bone structures and surrounding soft tissue interface. This salient bone edge information is further enhanced using a sparse gradient counting method based on L₀ gradient minimization, which globally controls how many nonzero gradients are resulted in order to approximate prominent bone structures in a structure-sparsity-management manner. The last stage of the framework involves incorporation of local phase bone boundary information in order to provide an intensity invariant enhancement of contrast between the bone and surrounding soft tissue. The enhanced images are segmented using a fast random walker algorithm. Validation against expert segmentation was performed on 20 clinical knee MRI volumes and achieved a mean dice similarity coefficient of 0.949.

In the assessment of nodules in CT scans of the lungs, a number of image-derived features are diagnostically relevant. Currently, many of these features are defined only qualitatively, so they are difficult to quantify from first principles. Nevertheless, these features (through their qualitative definitions and interpretations thereof) are often quantified via a variety of mathematical methods for the purpose of computer-aided diagnosis (CAD). To determine the potential usefulness of quantified diagnostic image features as inputs to a CAD system, we investigate the predictive capability of statistical learning methods for classifying nodule malignancy. We utilize the Lung Image Database Consortium dataset and only employ the radiologist-assigned diagnostic feature values for the lung nodules therein, as well as our derived estimates of the diameter and volume of the nodules from the radiologists’ annotations. We calculate theoretical upper bounds on the classification accuracy that are achievable by an ideal classifier that only uses the radiologist-assigned feature values, and we obtain an accuracy of 85.74 (±1.14)%, which is, on average, 4.43% below the theoretical maximum of 90.17%. The corresponding area-under-the-curve (AUC) score is 0.932 (±0.012), which increases to 0.949 (±0.007) when diameter and volume features are included and has an accuracy of 88.08 (±1.11)%. Our results are comparable to those in the literature that use algorithmically derived image-based features, which supports our hypothesis that lung nodules can be classified as malignant or benign using only quantified, diagnostic image features, and indicates the competitiveness of this approach. We also analyze how the classification accuracy depends on specific features and feature subsets, and we rank the features according to their predictive power, statistically demonstrating the top four to be spiculation, lobulation, subtlety, and calcification.

Retinopathy of prematurity (ROP), a disorder of the retina occurring in preterm infants, is the leading cause of preventable childhood blindness. An active phase of ROP that requires treatment is associated with the presence of plus disease, which is diagnosed clinically in a qualitative manner by visual assessment of the existence of a certain level of increase in the thickness and tortuosity of retinal vessels. The present study performs computer-aided diagnosis (CAD) of plus disease via quantitative measurement of tortuosity in retinal fundus images of preterm infants. Digital image processing techniques were developed for the detection of retinal vessels and measurement of their tortuosity. The total lengths of abnormally tortuous vessels in each quadrant and the entire image were then computed. A minimum-length diagnostic-decision-making criterion was developed to assess the diagnostic sensitivity and specificity of the values obtained. The area (A_z) under the receiver operating characteristic curve was used to assess the overall diagnostic accuracy of the methods. Using a set of 19 retinal fundus images of preterm infants with plus disease and 91 without plus disease, the proposed methods provided an overall diagnostic accuracy of A_z=0.98. Using the total length of all abnormally tortuous vessel segments in an image, our techniques are capable of CAD of plus disease with high accuracy without the need for manual selection of vessels to analyze. The proposed methods may be used in a clinical or teleophthalmological setting.

The purpose of this work is to describe the LUNGx Challenge for the computerized classification of lung nodules on diagnostic computed tomography (CT) scans as benign or malignant and report the performance of participants’ computerized methods along with that of six radiologists who participated in an observer study performing the same Challenge task on the same dataset. The Challenge provided sets of calibration and testing scans, established a performance assessment process, and created an infrastructure for case dissemination and result submission. Ten groups applied their own methods to 73 lung nodules (37 benign and 36 malignant) that were selected to achieve approximate size matching between the two cohorts. Area under the receiver operating characteristic curve (AUC) values for these methods ranged from 0.50 to 0.68; only three methods performed statistically better than random guessing. The radiologists’ AUC values ranged from 0.70 to 0.85; three radiologists performed statistically better than the best-performing computer method. The LUNGx Challenge compared the performance of computerized methods in the task of differentiating benign from malignant lung nodules on CT scans, placed in the context of the performance of radiologists on the same task. The continued public availability of the Challenge cases will provide a valuable resource for the medical imaging research community.

A three-dimensional breast density estimation method is presented for high spectral and spatial resolution (HiSS) MR imaging. Twenty-two patients were recruited (under an Institutional Review Board--approved Health Insurance Portability and Accountability Act-compliant protocol) for high-risk breast cancer screening. Each patient received standard-of-care clinical digital x-ray mammograms and MR scans, as well as HiSS scans. The algorithm for breast density estimation includes breast mask generating, breast skin removal, and breast percentage density calculation. The inter- and intra-user variabilities of the HiSS-based density estimation were determined using correlation analysis and limits of agreement. Correlation analysis was also performed between the HiSS-based density estimation and radiologists’ breast imaging-reporting and data system (BI-RADS) density ratings. A correlation coefficient of 0.91 (p<0.0001) was obtained between left and right breast density estimations. An interclass correlation coefficient of 0.99 (p<0.0001) indicated high reliability for the inter-user variability of the HiSS-based breast density estimations. A moderate correlation coefficient of 0.55 (p=0.0076) was observed between HiSS-based breast density estimations and radiologists’ BI-RADS. In summary, an objective density estimation method using HiSS spectral data from breast MRI was developed. The high reproducibility with low inter- and low intra-user variabilities shown in this preliminary study suggest that such a HiSS-based density metric may be potentially beneficial in programs requiring breast density such as in breast cancer risk assessment and monitoring effects of therapy.

The purpose of this work was to develop a clinically viable laparoscopic augmented reality (AR) system employing stereoscopic (3-D) vision, laparoscopic ultrasound (LUS), and electromagnetic (EM) tracking to achieve image registration. We investigated clinically feasible solutions to mount the EM sensors on the 3-D laparoscope and the LUS probe. This led to a solution of integrating an externally attached EM sensor near the imaging tip of the LUS probe, only slightly increasing the overall diameter of the probe. Likewise, a solution for mounting an EM sensor on the handle of the 3-D laparoscope was proposed. The spatial image-to-video registration accuracy of the AR system was measured to be 2.59±0.58  mm and 2.43±0.48  mm for the left- and right-eye channels, respectively. The AR system contributed 58-ms latency to stereoscopic visualization. We further performed an animal experiment to demonstrate the use of the system as a visualization approach for laparoscopic procedures. In conclusion, we have developed an integrated, compact, and EM tracking-based stereoscopic AR visualization system, which has the potential for clinical use. The system has been demonstrated to achieve clinically acceptable accuracy and latency. This work is a critical step toward clinical translation of AR visualization for laparoscopic procedures.

Systemic hypertension is a causative factor in left ventricular hypertrophy (LVH). This study is motivated by the potential to reverse or manage the dysfunction associated with structural remodeling of the myocardium in this pathology. Using diffusion tensor magnetic resonance imaging, we present an analysis of myocardial fiber and laminar sheet orientation in ex vivo hypertrophic (6 SHR) and normal (5 WKY) rat hearts using the covariance of the diffusion tensor. First, an atlas of normal cardiac microstructure was formed using the WKY b0 images. Then, the SHR and WKY b0 hearts were registered to the atlas. The acquired deformation fields were applied to the SHR and WKY heart tensor fields followed by the preservation of principal direction (PPD) reorientation strategy. A mean tensor field was then formed from the registered WKY tensor images. Calculating the covariance of the registered tensor images about this mean for each heart, the hypertrophic myocardium exhibited significantly increased myocardial fiber derangement (p=0.017) with a mean dispersion of 38.7 deg, and an increased dispersion of the laminar sheet normal (p=0.030) of 54.8 deg compared with 34.8 deg and 51.8 deg, respectively, in the normal hearts. Results demonstrate significantly altered myocardial fiber and laminar sheet structure in rats with hypertensive LVH.

Prostate segmentation on T2w MRI is important for several diagnostic and therapeutic procedures for prostate cancer. Manual segmentation is time-consuming, labor-intensive, and subject to high interobserver variability. This study investigated the suitability of computer-assisted segmentation algorithms for clinical translation, based on measurements of interoperator variability and measurements of the editing time required to yield clinically acceptable segmentations. A multioperator pilot study was performed under three pre- and postediting conditions: manual, semiautomatic, and automatic segmentation. We recorded the required editing time for each segmentation and measured the editing magnitude based on five different spatial metrics. We recorded average editing times of 213, 328, and 393 s for manual, semiautomatic, and automatic segmentation respectively, while an average fully manual segmentation time of 564 s was recorded. The reduced measured postediting interoperator variability of semiautomatic and automatic segmentations compared to the manual approach indicates the potential of computer-assisted segmentation for generating a clinically acceptable segmentation faster with higher consistency. The lack of strong correlation between editing time and the values of typically used error metrics (ρ<0.5) implies that the necessary postsegmentation editing time needs to be measured directly in order to evaluate an algorithm’s suitability for clinical translation.

The aim of this study is to compare longitudinal two-dimensional (2-D) and three-dimensional (3-D) ultrasound (US) estimates of ventricle size in preterm neonates with posthemorrhagic ventricular dilatation (PHVD) using quantitative measurements of the lateral ventricles. Cranial 2-D US and 3-D US images were acquired from neonatal patients with diagnosed PHVD within 10 min of each other one to two times per week and analyzed offline. Ventricle index, anterior horn width, third ventricle width, and thalamo-occipital distance were measured on the 2-D images and ventricle volume (VV) was measured from 3-D US images. Changes in the measurements between successive image sets were also recorded. No strong correlations were found between VV and 2-D US measurements (R² between 0.69 and 0.36). Additionally, weak correlations were found between changes in 2-D US measurements and 3-D US VV (R² between 0.13 and 0.02). A trend was found between increasing 2-D US measurements and 3-D US-based VV, but this was not the case when comparing changes between 3-D US VV and 2-D US measurements. If 3-D US-based VV provides a more accurate estimate of ventricle size than 2-D US measurements, moderate–weak correlations with 3-D US suggest that monitoring preterm patients with PHVD using 2-D US measurements alone might not accurately represent whether the ventricles are progressively dilating. A volumetric measure (3-D US or MRI) could be used instead to more accurately represent changes.

In-depth understanding of the diaphragm’s anatomy and physiology has been of great interest to the medical community, as it is the most important muscle of the respiratory system. While noncontrast four-dimensional (4-D) computed tomography (CT) imaging provides an interesting opportunity for effective acquisition of anatomical and/or functional information from a single modality, segmenting the diaphragm in such images is very challenging not only because of the diaphragm’s lack of image contrast with its surrounding organs but also because of respiration-induced motion artifacts in 4-D CT images. To account for such limitations, we present an automatic segmentation algorithm, which is based on a priori knowledge of diaphragm anatomy. The novelty of the algorithm lies in using the diaphragm’s easy-to-segment contacting organs—including the lungs, heart, aorta, and ribcage—to guide the diaphragm’s segmentation. Obtained results indicate that average mean distance to the closest point between diaphragms segmented using the proposed technique and corresponding manual segmentation is 2.55±0.39  mm, which is favorable. An important feature of the proposed technique is that it is the first algorithm to delineate the entire diaphragm. Such delineation facilitates applications, where the diaphragm boundary conditions are required such as biomechanical modeling for in-depth understanding of the diaphragm physiology.

Multipath scattering, or reverberation, takes a substantial toll on image quality in many clinical exams. We have suggested a model-based solution to this problem, which we refer to as aperture domain model image reconstruction (ADMIRE). For ADMIRE to work well, it must be trained with precisely characterized data. To solve this specific problem and the general problem of efficiently simulating reverberation, we propose an approach to simulate reverberation with linear simulation tools. Our simulation method defines total propagation time, first scattering site, and a final scattering site. We use a linear simulation package, such as Field II, to simulate scattering from the final site and then shift the simulated wavefront later in time based on the total propagation time and the geometry of the first scattering site. We validate our simulations using theoretical descriptions of clutter in the literature and data acquired from ex vivo tissue. We found that ex vivo tissue clutter had a mean speckle SNR of 1.40±0.23, which we could simulate with about 2 scatterers per resolution cell. Axial clutter distributions drawn from an exponential distribution with a mean of 5 mm and at least 0.5 scatters per resolution cell resulted in clutter that was statistically indistinguishable from the van Cittert–Zernike behavior predicted by literature.

The registration of two-dimensional histology images to reference images from other modalities is an important preprocessing step in the reconstruction of three-dimensional histology volumes. This is a challenging problem because of the differences in the appearances of histology images and other modalities, and the presence of large nonrigid deformations which occur during slide preparation. This paper shows the feasibility of using densely sampled scale-invariant feature transform (SIFT) features and a SIFTFlow deformable registration algorithm for coregistering whole-mount histology images with blockface optical images. We present a method for jointly optimizing the regularization parameters used by the SIFTFlow objective function and use it to determine the most appropriate values for the registration of breast lumpectomy specimens. We demonstrate that tuning the regularization parameters results in significant improvements in accuracy and we also show that SIFTFlow outperforms a previously described edge-based registration method. The accuracy of the histology images to blockface images registration using the optimized SIFTFlow method was assessed using an independent test set of images from five different lumpectomy specimens and the mean registration error was 0.32±0.22  mm.

Quantitative histomorphometry (QH) is the process of computerized feature extraction from digitized tissue slide images to predict disease presence, behavior, and outcome. Feature stability between sites may be compromised by laboratory-specific variables including dye batch, slice thickness, and the whole slide scanner used. We present two new measures, preparation-induced instability score and latent instability score, to quantify feature instability across and within datasets. In a use case involving prostate cancer, we examined QH features which may detect cancer on whole slide images. Using our method, we found that five feature families (graph, shape, co-occurring gland tensor, sub-graph, and texture) were different between datasets in 19.7% to 48.6% of comparisons while the values expected without site variation were 4.2% to 4.6%. Color normalizing all images to a template did not reduce instability. Scanning the same 34 slides on three scanners demonstrated that Haralick features were most substantively affected by scanner variation, being unstable in 62% of comparisons. We found that unstable feature families performed significantly worse in inter- than intrasite classification. Our results appear to suggest QH features should be evaluated across sites to assess robustness, and class discriminability alone should not represent the benchmark for digital pathology feature selection.

This PDF file contains the errata for “JMI Vol. 3 Issue 04 Paper JMI-2016-1013-ERR” for JMI Vol. 3 Issue 04

This PDF file contains the errata for “JMI Vol. 3 Issue 04 Paper JMI-2016-1208-ERR” for JMI Vol. 3 Issue 04