The effectiveness of phase contrast X-ray computed tomography (PCI-CT) in visualizing human patellar cartilage matrix has been demonstrated due to its ability to capture soft tissue contrast on a micrometer resolution scale. Recent studies have shown that off-the-shelf Convolutional Neural Network (CNN) features learned from a nonmedical data set can be used for medical image classification. In this paper, we investigate the ability of features extracted from two different CNNs for characterizing chondrocyte patterns in the cartilage matrix. We obtained features from 842 regions of interest annotated on PCI-CT images of human patellar cartilage using CaffeNet and Inception-v3 Network, which were then used in a machine learning task involving support vector machines with radial basis function kernel to classify the ROIs as healthy or osteoarthritic. Classification performance was evaluated using the area (AUC) under the Receiver Operating Characteristic (ROC) curve. The best classification performance was observed with features from Inception-v3 network (AUC = 0.95), which outperforms features extracted from CaffeNet (AUC = 0.91). These results suggest that such characterization of chondrocyte patterns using features from internal layers of CNNs can be used to distinguish between healthy and osteoarthritic tissue with high accuracy.
We investigate the applicability of a computational framework, called mutual connectivity analysis (MCA), for directed functional connectivity analysis in both synthetic and resting-state functional MRI data. This framework comprises of first evaluating non-linear cross-predictability between every pair of time series prior to recovering the underlying network structure using community detection algorithms. We obtain the non-linear cross-prediction score between time series using Generalized Radial Basis Functions (GRBF) neural networks. These cross-prediction scores characterize the underlying functionally connected networks within the resting brain, which can be extracted using non-metric clustering approaches, such as the Louvain method. We first test our approach on synthetic models with known directional influence and network structure. Our method is able to capture the directional relationships between time series (with an area under the ROC curve = 0.92 ± 0.037) as well as the underlying network structure (Rand index = 0.87 ± 0.063) with high accuracy. Furthermore, we test this method for network recovery on resting-state fMRI data, where results are compared to the motor cortex network recovered from a motor stimulation sequence, resulting in a strong agreement between the two (Dice coefficient = 0.45). We conclude that our MCA approach is effective in analyzing non-linear directed functional connectivity and in revealing underlying functional network structure in complex systems.
KEYWORDS: Functional magnetic resonance imaging, Brain, Statistical analysis, Time series analysis, Neuroimaging, Neurological disorders, Magnetic resonance imaging, Error analysis, Functional imaging, Data modeling, Radiology, Control systems, Biological research, Biomedical optics
The use of functional Magnetic Resonance Imaging (fMRI) has provided interesting insights into our understanding of the brain. In clinical setups these scans have been used to detect and study changes in the brain network properties in various neurological disorders. A large percentage of subjects infected with HIV present cognitive deficits, which are known as HIV associated neurocognitive disorder (HAND). In this study we propose to use our novel technique named Mutual Connectivity Analysis (MCA) to detect differences in brain networks in subjects with and without HIV infection. Resting state functional MRI scans acquired from 10 subjects (5 HIV+ and 5 HIV-) were subject to standard preprocessing routines. Subsequently, the average time-series for each brain region of the Automated Anatomic Labeling (AAL) atlas are extracted and used with the MCA framework to obtain a graph characterizing the interactions between them. The network graphs obtained for different subjects are then compared using Network-Based Statistics (NBS), which is an approach to detect differences between graphs edges while controlling for the family-wise error rate when mass univariate testing is performed. Applying this approach on the graphs obtained yields a single network encompassing 42 nodes and 65 edges, which is significantly different between the two subject groups. Specifically connections to the regions in and around the basal ganglia are significantly decreased. Also some nodes corresponding to the posterior cingulate cortex are affected. These results are inline with our current understanding of pathophysiological mechanisms of HIV associated neurocognitive disease (HAND) and other HIV based fMRI connectivity studies. Hence, we illustrate the applicability of our novel approach with network-based statistics in a clinical case-control study to detect differences connectivity patterns.
KEYWORDS: Brain, Functional magnetic resonance imaging, Magnetic resonance imaging, Time series analysis, Neural networks, Brain imaging, Brain mapping, Radiology, Model-based design, Neurons, Biomedical optics, Control systems
About 50% of subjects infected with HIV present deficits in cognitive domains, which are known collectively as HIV associated neurocognitive disorder (HAND). The underlying synaptodendritic damage can be captured using resting state functional MRI, as has been demonstrated by a few earlier studies. Such damage may induce topological changes of brain connectivity networks. We test this hypothesis by capturing the functional interdependence of 90 brain network nodes using a Mutual Connectivity Analysis (MCA) framework with non-linear time series modeling based on Generalized Radial Basis function (GRBF) neural networks. The network nodes are selected based on the regions defined in the Automated Anatomic Labeling (AAL) atlas. Each node is represented by the average time series of the voxels of that region. The resulting networks are then characterized using graph-theoretic measures that quantify various network topology properties at a global as well as at a local level. We tested for differences in these properties in network graphs obtained for 10 subjects (6 male and 4 female, 5 HIV+ and 5 HIV-). Global network properties captured some differences between these subject cohorts, though significant differences were seen only with the clustering coefficient measure. Local network properties, such as local efficiency and the degree of connections, captured significant differences in regions of the frontal lobe, precentral and cingulate cortex amongst a few others. These results suggest that our method can be used to effectively capture differences occurring in brain network connectivity properties revealed by resting-state functional MRI in neurological disease states, such as HAND.
The current clinical standard for measuring Bone Mineral Density (BMD) is dual X-ray absorptiometry, however more recently BMD derived from volumetric quantitative computed tomography has been shown to demonstrate a high association with spinal fracture susceptibility. In this study, we propose a method of fracture risk assessment using structural properties of trabecular bone in spinal vertebrae. Experimental data was acquired via axial multi-detector CT (MDCT) from 12 spinal vertebrae specimens using a whole-body 256-row CT scanner with a dedicated calibration phantom. Common image processing methods were used to annotate the trabecular compartment in the vertebral slices creating a circular region of interest (ROI) that excluded cortical bone for each slice. The pixels inside the ROI were converted to values indicative of BMD. High dimensional geometrical features were derived using the scaling index method (SIM) at different radii and scaling factors (SF). The mean BMD values within the ROI were then extracted and used in conjunction with a support vector machine to predict the failure load of the specimens. Prediction performance was measured using the root-mean-square error (RMSE) metric and determined that SIM combined with mean BMD features (RMSE = 0.82 ± 0.37) outperformed MDCT-measured mean BMD (RMSE = 1.11 ± 0.33) (p < 10-4). These results demonstrate that biomechanical strength prediction in vertebrae can be significantly improved through the use of SIM-derived texture features from trabecular bone.
Phase contrast X-ray computed tomography (PCI-CT) has recently emerged as a novel imaging technique that allows visualization of cartilage soft tissue, subsequent examination of chondrocyte patterns, and their correlation to osteoarthritis. Previous studies have shown that 2D texture features are effective at distinguishing between healthy and osteoarthritic regions of interest annotated in the radial zone of cartilage matrix on PCI-CT images. In this study, we further extend the texture analysis to 3D and investigate the ability of volumetric texture features at characterizing chondrocyte patterns in the cartilage matrix for purposes of classification. Here, we extracted volumetric texture features derived from Minkowski Functionals and gray-level co-occurrence matrices (GLCM) from 496 volumes of interest (VOI) annotated on PCI-CT images of human patellar cartilage specimens. The extracted features were then used in a machine-learning task involving support vector regression to classify ROIs as healthy or osteoarthritic. Classification performance was evaluated using the area under the receiver operating characteristic (ROC) curve (AUC). The best classification performance was observed with GLCM features correlation (AUC = 0.83 ± 0.06) and homogeneity (AUC = 0.82 ± 0.07), which significantly outperformed all Minkowski Functionals (p < 0.05). These results suggest that such quantitative analysis of chondrocyte patterns in human patellar cartilage matrix involving GLCM-derived statistical features can distinguish between healthy and osteoarthritic tissue with high accuracy.
We explore a computational framework for functional connectivity analysis in resting-state functional MRI (fMRI) data acquired from the human brain for recovering the underlying network structure and understanding causality between network components. Termed mutual connectivity analysis (MCA), this framework involves two steps, the first of which is to evaluate the pair-wise cross-prediction performance between fMRI pixel time series within the brain. In a second step, the underlying network structure is subsequently recovered from the affinity matrix using non-metric network clustering approaches, such as the so-called Louvain method. Finally, we use convergent cross-mapping (CCM) to study causality between different network components. We demonstrate our MCA framework in the problem of recovering the motor cortex network associated with hand movement from resting state fMRI data. Results are compared with a ground truth of active motor cortex regions as identified by a task-based fMRI sequence involving a finger-tapping stimulation experiment. Our results regarding causation between regions of the motor cortex revealed a significant directional variability and were not readily interpretable in a consistent manner across subjects. However, our results on whole-slice fMRI analysis demonstrate that MCA-based model-free recovery of regions associated with the primary motor cortex and supplementary motor area are in close agreement with localization of similar regions achieved with a task-based fMRI acquisition. Thus, we conclude that our MCA methodology can extract and visualize valuable information concerning the underlying network structure between different regions of the brain in resting state fMRI.
KEYWORDS: Functional magnetic resonance imaging, Neurons, Brain, Magnetic resonance imaging, Visualization, Radiology, Neural networks, Linear filtering, Analytical research, Data acquisition
Echo state networks (ESN) are recurrent neural networks where the hidden layer is replaced with a fixed reservoir of neurons. Unlike feed-forward networks, neuron training in ESN is restricted to the output neurons alone thereby providing a computational advantage. We demonstrate the use of such ESNs in our mutual connectivity analysis (MCA) framework for recovering the primary motor cortex network associated with hand movement from resting state functional MRI (fMRI) data. Such a framework consists of two steps - (1) defining a pair-wise affinity matrix between different pixel time series within the brain to characterize network activity and (2) recovering network components from the affinity matrix with non-metric clustering. Here, ESNs are used to evaluate pair-wise cross-estimation performance between pixel time series to create the affinity matrix, which is subsequently subject to non-metric clustering with the Louvain method. For comparison, the ground truth of the motor cortex network structure is established with a task-based fMRI sequence. Overlap between the primary motor cortex network recovered with our model free MCA approach and the ground truth was measured with the Dice coefficient. Our results show that network recovery with our proposed MCA approach is in close agreement with the ground truth. Such network recovery is achieved without requiring low-pass filtering of the time series ensembles prior to analysis, an fMRI preprocessing step that has courted controversy in recent years. Thus, we conclude our MCA framework can allow recovery and visualization of the underlying functionally connected networks in the brain on resting state fMRI.
While the proximal femur is preferred for measuring bone mineral density (BMD) in fracture risk estimation, the introduction of volumetric quantitative computed tomography has revealed stronger associations between BMD and spinal fracture status. In this study, we propose to capture properties of trabecular bone structure in spinal vertebrae with advanced second-order statistical features for purposes of fracture risk assessment. For this purpose, axial multi-detector CT (MDCT) images were acquired from 28 spinal vertebrae specimens using a whole-body 256-row CT scanner with a dedicated calibration phantom. A semi-automated method was used to annotate the trabecular compartment in the central vertebral slice with a circular region of interest (ROI) to exclude cortical bone; pixels within were converted to values indicative of BMD. Six second-order statistical features derived from gray-level co-occurrence matrices (GLCM) and the mean BMD within the ROI were then extracted and used in conjunction with a generalized radial basis functions (GRBF) neural network to predict the failure load of the specimens; true failure load was measured through biomechanical testing. Prediction performance was evaluated with a root-mean-square error (RMSE) metric. The best prediction performance was observed with GLCM feature ‘correlation’ (RMSE = 1.02 ± 0.18), which significantly outperformed all other GLCM features (p < 0.01). GLCM feature correlation also significantly outperformed MDCTmeasured mean BMD (RMSE = 1.11 ± 0.17) (p< 10-4). These results suggest that biomechanical strength prediction in spinal vertebrae can be significantly improved through characterization of trabecular bone structure with GLCM-derived texture features.
Functional MRI (fMRI) is currently used to investigate structural and functional connectivity in human brain networks. To this end, previous studies have proposed computational methods that involve assumptions that can induce information loss, such as assumed linear coupling of the fMRI signals or requiring dimension reduction. This study presents a new computational framework for investigating the functional connectivity in the brain and recovering network structure while reducing the information loss inherent in previous methods. For this purpose, pair-wise mutual information (MI) was extracted from all pixel time series within the brain on resting-state fMRI data. Non-metric topographic mapping of proximity (TMP) data was subsequently applied to recover network structure from the pair-wise MI analysis. Our computational framework is demonstrated in the task of identifying regions of the primary motor cortex network on resting state fMRI data. For ground truth comparison, we also localized regions of the primary motor cortex associated with hand movement in a task-based fMRI sequence with a finger-tapping stimulus function. The similarity between our pair-wise MI clustering results and the ground truth is evaluated using the dice coefficient. Our results show that non-metric clustering with the TMP algorithm, as performed on pair-wise MI analysis, was able to detect the primary motor cortex network and achieved a dice coefficient of 0.53 in terms of overlap with the ground truth. Thus, we conclude that our computational framework can extract and visualize valuable information concerning the underlying network structure between different regions of the brain in resting state fMRI.
Cone beam computed tomography (CBCT) has found use in mammography for imaging the entire breast with sufficient spatial resolution at a radiation dose within the range of that of conventional mammography. Recently, enhancement of lesion tissue through the use of contrast agents has been proposed for cone beam CT. This study investigates whether the use of such contrast agents improves the ability of texture features to differentiate lesion texture from healthy tissue on CBCT in an automated manner. For this purpose, 9 lesions were annotated by an experienced radiologist on both regular and contrast-enhanced CBCT images using two-dimensional (2D) square ROIs. These lesions were then segmented, and each pixel within the lesion ROI was assigned a label – lesion or non-lesion, based on the segmentation mask. On both sets of CBCT images, four three-dimensional (3D) Minkowski Functionals were used to characterize the local topology at each pixel. The resulting feature vectors were then used in a machine learning task involving support vector regression with a linear kernel (SVRlin) to classify each pixel as belonging to the lesion or non-lesion region of the ROI. Classification performance was assessed using the area under the receiver-operating characteristic (ROC) curve (AUC). Minkowski Functionals derived from contrastenhanced CBCT images were found to exhibit significantly better performance at distinguishing between lesion and non-lesion areas within the ROI when compared to those extracted from CBCT images without contrast enhancement (p < 0.05). Thus, contrast enhancement in CBCT can improve the ability of texture features to distinguish lesions from surrounding healthy tissue.
The ability of Anisotropic Minkowski Functionals (AMFs) to capture local anisotropy while evaluating topological properties of the underlying gray-level structures has been previously demonstrated. We evaluate the ability of this approach to characterize local structure properties of trabecular bone micro-architecture in ex vivo proximal femur specimens, as visualized on multi-detector CT, for purposes of biomechanical bone strength prediction. To this end, volumetric AMFs were computed locally for each voxel of volumes of interest (VOI) extracted from the femoral head of 146 specimens. The local anisotropy captured by such AMFs was quantified using a fractional anisotropy measure; the magnitude and direction of anisotropy at every pixel was stored in histograms that served as a feature vectors that characterized the VOIs. A linear multi-regression analysis algorithm was used to predict the failure load (FL) from the feature sets; the predicted FL was compared to the true FL determined through biomechanical testing. The prediction performance was measured by the root mean square error (RMSE) for each feature set. The best prediction performance was obtained from the fractional anisotropy histogram of AMF Euler Characteristic (RMSE = 1.01 ± 0.13), which was significantly better than MDCT-derived mean BMD (RMSE = 1.12 ± 0.16, p<0.05). We conclude that such anisotropic Minkowski Functionals can capture valuable information regarding regional trabecular bone quality and contribute to improved bone strength prediction, which is important for improving the clinical assessment of osteoporotic fracture risk.
The analysis of large ensembles of time series is a fundamental challenge in different domains of biomedical image processing applications, specifically in the area of functional MRI data processing. An important aspect of such analysis is the ability to reconstruct community network structures based on interactive behavior between different nodes of the network which are captured in such time series. In this study, we start with a previously proposed novel approach that applies the linear Granger Causality concept to very high-dimensional time series. This approach is based on integrating dimensionality reduction into a multivariate time series model. If residuals of dimensionality reduced models can be transformed back into the original space, prediction errors in the high–dimensional space may be computed, and a large scale Granger Causality Index (lsGCI) is properly defined. The primary goal of this study was then to present an approach for recovering network structure from such lsGCI interactions through the application of pair-wise clustering. We specifically focus on a clustering approach based on topographic mapping of proximity data (TMP) for this purpose. We demonstrate our approach with a simulated network composed of five pair-wise different internal networks with varying strengths of community structure (based on the number of inter-network vertices). Our results suggest that such pair-wise clustering with TMP is capable of reconstructing the structure of the original network from lsGCI matrices that record the interactions between different nodes of the network when there is sufficient disparity between the intra- and inter-network vertices.
Regional trabecular bone quality estimation for purposes of femoral bone strength prediction is important for improving the clinical assessment of osteoporotic fracture risk. In this study, we explore the ability of 3D Minkowski Functionals derived from multi-detector computed tomography (MDCT) images of proximal femur specimens in predicting their corresponding biomechanical strength. MDCT scans were acquired for 50 proximal femur specimens harvested from human cadavers. An automated volume of interest (VOI)-fitting algorithm was used to define a consistent volume in the femoral head of each specimen. In these VOIs, the trabecular bone micro-architecture was characterized by statistical moments of its BMD distribution and by topological features derived from Minkowski Functionals. A linear multiregression analysis and a support vector regression (SVR) algorithm with a linear kernel were used to predict the failure load (FL) from the feature sets; the predicted FL was compared to the true FL determined through biomechanical testing. The prediction performance was measured by the root mean square error (RMSE) for each feature set. The best prediction result was obtained from the Minkowski Functional surface used in combination with SVR, which had the lowest prediction error (RMSE = 0.939 ± 0.345) and which was significantly lower than mean BMD (RMSE = 1.075 ± 0.279, p<0.005). Our results indicate that the biomechanical strength prediction can be significantly improved in proximal femur specimens with Minkowski Functionals extracted from on MDCT images used in conjunction with support vector regression.
Breast conserving therapy (BCT) of breast cancer is now widely accepted due to improved cosmetic outcome and improved patients’ quality of life. One of the critical issues in performing breast-conserving surgery is trying to achieve microscopically clear surgical margins while maintaining excellent cosmesis. Unfortunately, unacceptably close or positive surgical margins occur in at least 20-25% of all patients undergoing BCT requiring repeat surgical excision days or weeks later, as permanent histopathology routinely takes days to complete. Our aim is to develop a better method for intraoperative imaging of non-palpable breast malignancies excised by wire or needle localization. Providing non-deformed three dimensional imaging of the excised breast tissue should allow more accurate assessment of tumor margins and consequently allow further excision at the time of initial surgery thus limiting the enormous financial and emotional burden of additional surgery. We have designed and constructed a device that allows preservation of the excised breast tissue in its natural anatomic position relative to the breast as it is imaged to assess adequate excision. We performed initial tests with needle-guided lumpectomy specimens using micro-CT and digital breast tomosynthesis (DBT). Our device consists of a plastic sphere inside a cylindrical holder. The surgeon inserts a freshly excised piece of breast tissue into the sphere and matches its anatomic orientation with the fiducial markers on the sphere. A custom-shaped foam is placed inside the sphere to prevent specimen deformation due to gravity. DBT followed by micro-CT images of the specimen were obtained. We confirmed that our device preserved spatial orientation of the excised breast tissue and that the location error was lower than 10mm and 10 degrees. The initial obtained results indicate that breast lesions containing microcalcifications allow a good 3D imaging of margins providing immediate intraoperative feedback for further excision as needed at the initial operation.
Current assessment of cartilage is primarily based on identification of indirect markers such as joint space narrowing and increased subchondral bone density on x-ray images. In this context, phase contrast CT imaging (PCI-CT) has recently emerged as a novel imaging technique that allows a direct examination of chondrocyte patterns and their correlation to osteoarthritis through visualization of cartilage soft tissue. This study investigates the use of topological and geometrical approaches for characterizing chondrocyte patterns in the radial zone of the knee cartilage matrix in the presence and absence of osteoarthritic damage. For this purpose, topological features derived from Minkowski Functionals and geometric features derived from the Scaling Index Method (SIM) were extracted from 842 regions of interest (ROI) annotated on PCI-CT images of healthy and osteoarthritic specimens of human patellar cartilage. The extracted features were then used in a machine learning task involving support vector regression to classify ROIs as healthy or osteoarthritic. Classification performance was evaluated using the area under the receiver operating characteristic (ROC) curve (AUC). The best classification performance was observed with high-dimensional geometrical feature vectors derived from SIM (0.95 ± 0.06) which outperformed all Minkowski Functionals (p < 0.001). These results suggest that such quantitative analysis of chondrocyte patterns in human patellar cartilage matrix involving SIM-derived geometrical features can distinguish between healthy and osteoarthritic tissue with high accuracy.
We investigate the use of different trabecular bone descriptors and advanced machine learning techniques to complement standard bone mineral density (BMD) measures derived from dual-energy x-ray absorptiometry (DXA) for improving clinical assessment of osteoporotic fracture risk. For this purpose, volumes of interest were extracted from the head, neck, and trochanter of 146 ex vivo proximal femur specimens on multidetector computer tomography. The trabecular bone captured was characterized with (1) statistical moments of the BMD distribution, (2) geometrical features derived from the scaling index method (SIM), and (3) morphometric parameters, such as bone fraction, trabecular thickness, etc. Feature sets comprising DXA BMD and such supplemental features were used to predict the failure load (FL) of the specimens, previously determined through biomechanical testing, with multiregression and support vector regression. Prediction performance was measured by the root mean square error (RMSE); correlation with measured FL was evaluated using the coefficient of determination R 2 . The best prediction performance was achieved by a combination of DXA BMD and SIM-derived geometric features derived from the femoral head (RMSE: 0.869±0.121 , R 2 : 0.68±0.079 ), which was significantly better than DXA BMD alone (RMSE: 0.948±0.119 , R 2 : 0.61±0.101 ) (p<10 −4 ). For multivariate feature sets, SVR outperformed multiregression (p<0.05 ). These results suggest that supplementing standard DXA BMD measurements with sophisticated femoral trabecular bone characterization and supervised learning techniques can significantly improve biomechanical strength prediction in proximal femur specimens.
The current approach to evaluating cartilage degeneration at the knee joint requires visualization of the joint space on
radiographic images where indirect cues such as joint space narrowing serve as markers for osteoarthritis. A recent novel approach to visualizing the knee cartilage matrix using phase contrast imaging (PCI) with computed tomography (CT) was shown to allow direct examination of chondrocyte patterns and their subsequent correlation to osteoarthritis. This study aims to characterize chondrocyte cell patterns in the radial zone of the knee cartilage matrix in the presence and absence of osteoarthritic damage through texture analysis. Statistical features derived from gray-level co-occurrence matrices (GLCM) and geometric features derived from the Scaling Index Method (SIM) were extracted from 404 regions of interest (ROI) annotated on PCI images of healthy and osteoarthritic specimens of knee cartilage. These texture features were then used in a machine learning task to classify ROIs as healthy or osteoarthritic. A fuzzy k-nearest neighbor classifier was used and its performance was evaluated using the area under the Receiver Operating Characteristic (ROC) curve (AUC). The best classification performance was observed with high-dimensional
geometrical feature vectors derived from SIM and GLCM correlation features. With the experimental conditions used in
this study, both SIM and GLCM achieved a high classification performance (AUC value of 0.98) in the task of distinguishing between healthy and osteoarthritic ROIs. These results show that such quantitative analysis of
chondrocyte patterns in the knee cartilage matrix can distinguish between healthy and osteoarthritic tissue with high
accuracy.
Estimating local trabecular bone quality for purposes of femoral bone strength prediction is important for improving
the clinical assessment of osteoporotic hip fracture risk. In this study, we explore the ability of geometric features
derived from the Scaling Index Method (SIM) in predicting the biomechanical strength of proximal femur specimens
as visualized on multi-detector computed tomography (MDCT) images. MDCT scans were acquired for 50 proximal
femur specimens harvested from human cadavers. An automated volume of interest (VOI)-fitting algorithm was
used to define a consistent volume in the femoral head of each specimen. In these VOIs, the non-linear micro-structure of the trabecular bone was characterized by statistical moments of its BMD distribution and by local scaling properties derived from SIM. Linear multi-regression analysis and support vector regression with a linear kernel (SVRlin) were used to predict the failure load (FL) from the feature sets; the predicted FL was compared to the FL values determined through biomechanical testing. The prediction performance was measured by the root mean square error (RMSE) for each image feature on independent test set. The best prediction result was obtained from the SIM feature set with SVRlin, which had the lowest prediction error (RMSE = 0.842 ± 0.209) and which
was significantly lower than the conventionally used mean BMD (RMSE = 1.103 ± 0.262, , p<0.005). Our results indicate that the biomechanical strength prediction can be significantly improved in proximal femur specimens on MDCT images by using high-dimensional geometric features derived from SIM with support vector regression.
The ability of Minkowski Functionals to characterize local structure in different biological tissue types has been demonstrated in a variety of medical image processing tasks. We introduce anisotropic Minkowski Functionals (AMFs) as a novel variant that captures the inherent anisotropy of the underlying gray-level structures. To quantify the anisotropy characterized by our approach, we further introduce a method to compute a quantitative measure motivated by a technique utilized in MR diffusion tensor imaging, namely fractional anisotropy. We showcase the applicability of our method in the research context of characterizing the local structure properties of trabecular bone micro-architecture in the proximal femur as visualized on multi-detector CT. To this end, AMFs were computed locally for each pixel of ROIs extracted from the head, neck and trochanter regions. Fractional anisotropy was then used to quantify the local anisotropy of the trabecular structures found in these ROIs and to compare its distribution in different anatomical regions. Our results suggest a significantly greater concentration of anisotropic trabecular structures in the head and neck regions when compared to the trochanter region (p < 10-4). We also evaluated the ability of such AMFs to predict bone strength in the femoral head of proximal femur specimens obtained from 50 donors. Our results suggest that such AMFs, when used in conjunction with multi-regression models, can outperform more conventional features such as BMD in predicting failure load. We conclude that such anisotropic Minkowski Functionals can capture valuable information regarding directional attributes of local structure, which may be useful in a wide scope of biomedical imaging applications.
The current approach to evaluating cartilage degeneration at the knee joint requires visualization of the joint space on
radiographic images where indirect cues such as joint space narrowing serve as markers for osteoarthritis. A recent novel
approach to visualizing the knee cartilage matrix using phase contrast CT imaging (PCI-CT) was shown to allow direct
examination of chondrocyte cell patterns and their subsequent correlation to osteoarthritis. This study aims to
characterize chondrocyte cell patterns in the radial zone of the knee cartilage matrix in the presence and absence of
osteoarthritic damage through both gray-level co-occurrence matrix (GLCM) derived texture features as well as
Minkowski Functionals (MF). Thirteen GLCM and three MF texture features were extracted from 404 regions of interest
(ROI) annotated on PCI images of healthy and osteoarthritic specimens of knee cartilage. These texture features were
then used in a machine learning task to classify ROIs as healthy or osteoarthritic. A fuzzy k-nearest neighbor classifier
was used and its performance was evaluated using the area under the ROC curve (AUC). The best classification
performance was observed with the MF features 'perimeter' and 'Euler characteristic' and with GLCM correlation
features (f3 and f13). With the experimental conditions used in this study, both Minkowski Functionals and GLCM
achieved a high classification performance (AUC value of 0.97) in the task of distinguishing between health and
osteoarthritic ROIs. These results show that such quantitative analysis of chondrocyte patterns in the knee cartilage
matrix can distinguish between healthy and osteoarthritic tissue with high accuracy.
To improve the clinical assessment of osteoporotic hip fracture risk, recent computer-aided diagnosis systems
explore new approaches to estimate the local trabecular bone quality beyond bone density alone to predict femoral
bone strength. In this context, statistical bone mineral density (BMD) features extracted from multi-detector
computed tomography (MDCT) images of proximal femur specimens and different function approximations
methods were compared in their ability to predict the biomechanical strength. MDCT scans were acquired in
146 proximal femur specimens harvested from human cadavers. The femurs' failure load (FL) was determined
through biomechanical testing. An automated volume of interest (VOI)-fitting algorithm was used to define a
consistent volume in the femoral head of each specimen. In these VOIs, the trabecular bone was represented
by statistical moments of the BMD distribution and by pairwise spatial occurrence of BMD values using the
gray-level co-occurrence (GLCM) approach. A linear multi-regression analysis (MultiReg) and a support vector
regression algorithm with a linear kernel (SVRlin) were used to predict the FL from the image feature sets.
The prediction performance was measured by the root mean square error (RMSE) for each image feature on
independent test sets; in addition the coefficient of determination R2 was calculated. The best prediction
result was obtained with a GLCM feature set using SVRlin, which had the lowest prediction error (RSME =
1.040±0.143, R2 = 0.544) and which was significantly lower that the standard approach of using BMD.mean and
MultiReg (RSME = 1.093±0.133, R2 = 0.490, p<0.0001). The combined sets including BMD.mean and GLCM
features had a similar or slightly lower performance than using only GLCM features. The results indicate that the
performance of high-dimensional BMD features extracted from MDCT images in predicting the biomechanical
strength of proximal femur specimens can be significantly improved by using support vector regression.
The tumor extracellular matrix has been focused on by newer approaches to cancer therapy owing to its important
functions in the process of drug delivery and cellular metastasis. This study aims to characterize tumor extracellular
matrix structures in the presence and absence of therapy, as observed on second harmonic generation (SHG) images
through both gray-level co-occurrence matrix (GLCM) derived texture features as well as Minkowski Functionals (MF)
that focus on the underlying gray-level topology and geometry of the texture patterns. Thirteen GLCM texture features
and three MF texture features were extracted from 119 regions of interest (ROI) annotated on SHG images of treated and
control samples of tumor extracellular matrix. These texture features were then used in a machine learning task to
classify ROIs as belonging to treated or control samples. A fuzzy k-nearest neighbor classifier was optimized using
random sub-sampling cross-validation for each texture feature and the classification performance was calculated on an
independent test set using the area under the ROC curve (AUC); AUC distributions of different features were compared
using a Mann-Whitney U-test. Two GLCM features f3 and f13 exhibited a significantly higher classification
performance when compared to other GLCM features (p < 0.05). The MF feature Area exhibited the best classification
performance among the MF features while also being comparable to that obtained with the best GLCM features. These
results show that both statistical and topological texture features can be used as quantitative measures is evaluating the
effects of therapy on the tumor extracellular matrix.
Morphological characterization of lesions on dynamic breast MRI exams through texture analysis has typically involved
the computation of gray-level co-occurrence matrices (GLCM), which serve as the basis for second order statistical
texture features. This study aims to characterize lesion morphology through the underlying topology and geometry with
Minkowski Functionals (MF) and investigate the impact of using such texture features extracted dynamically over a time
series in classifying benign and malignant lesions. 60 lesions (28 malignant & 32 benign) were identified and annotated
by experienced radiologists on 54 breast MRI exams of female patients where histopathological reports were available
prior to this investigation. 13 GLCM-derived texture features and 3 MF features were then extracted from lesion ROIs
on all five post-contrast images. These texture features were combined into high dimensional texture feature vectors and
used in a lesion classification task. A fuzzy k-nearest neighbor classifier was optimized using random sub-sampling
cross-validation for each texture feature and the classification performance was calculated on an independent test set
using the area under the ROC curve (AUC); AUC distributions of different features were compared using a Mann-
Whitney U-test. The MF feature 'Area' exhibited significantly improvements in classification performance (p<0.05)
when compared to all GLCM-derived features while the MF feature 'Perimeter' significantly outperformed 12 out of 13
GLCM features (p<0.05) in the lesion classification task. These results show that dynamic texture tracking of
morphological characterization that relies on topological texture features can contribute to better lesion character
classification.
Local scaling properties of texture regions were compared in their ability to classify morphological patterns
known as 'honeycombing' that are considered indicative for the presence of fibrotic interstitial lung diseases
in high-resolution computed tomography (HRCT) images. For 14 patients with known occurrence of honeycombing,
a stack of 70 axial, lung kernel reconstructed images were acquired from HRCT chest exams. 241
regions of interest of both healthy and pathological (89) lung tissue were identified by an experienced radiologist.
Texture features were extracted using six properties calculated from gray-level co-occurrence matrices (GLCM),
Minkowski Dimensions (MDs), and the estimation of local scaling properties with Scaling Index Method (SIM).
A k-nearest-neighbor (k-NN) classifier and a Multilayer Radial Basis Functions Network (RBFN) were optimized
in a 10-fold cross-validation for each texture vector, and the classification accuracy was calculated on independent
test sets as a quantitative measure of automated tissue characterization. A Wilcoxon signed-rank test was used
to compare two accuracy distributions including the Bonferroni correction. The best classification results were
obtained by the set of SIM features, which performed significantly better than all the standard GLCM and
MD features (p < 0.005) for both classifiers with the highest accuracy (94.1%, 93.7%; for the k-NN and RBFN
classifier, respectively). The best standard texture features were the GLCM features 'homogeneity' (91.8%,
87.2%) and 'absolute value' (90.2%, 88.5%). The results indicate that advanced texture features using local
scaling properties can provide superior classification performance in computer-assisted diagnosis of interstitial
lung diseases when compared to standard texture analysis methods.
The Generalized Matrix Learning Vector Quantization (GMLVQ) is used to estimate the relevance of texture
features in their ability to classify interstitial lung disease patterns in high-resolution computed tomography
(HRCT) images. After a stochastic gradient descent, the GMLVQ algorithm provides a discriminative distance
measure of relevance factors, which can account for pairwise correlations between different texture features and
their importance for the classification of healthy and diseased patterns. Texture features were extracted from
gray-level co-occurrence matrices (GLCMs), and were ranked and selected according to their relevance obtained
by GMLVQ and, for comparison, to a mutual information (MI) criteria. A k-nearest-neighbor (kNN) classifier
and a Support Vector Machine with a radial basis function kernel (SVMrbf) were optimized in a 10-fold crossvalidation
for different texture feature sets. In our experiment with real-world data, the feature sets selected by
the GMLVQ approach had a significantly better classification performance compared with feature sets selected
by a MI ranking.
Haralick texture features derived from gray-level co-occurrence matrices (GLCM) were used to classify the character of
suspicious breast lesions as benign or malignant on dynamic contrast-enhanced MRI studies. Lesions were identified and
annotated by an experienced radiologist on 54 MRI exams of female patients where histopathological reports were
available prior to this investigation. GLCMs were then extracted from these 2D regions of interest (ROI) for four
principal directions (0°, 45°, 90° & 135°) and used to compute Haralick texture features. A fuzzy k-nearest neighbor (k-
NN) classifier was optimized in ten-fold cross-validation for each texture feature and the classification performance was
calculated on an independent test set as a function of area under the ROC curve. The lesion ROIs were characterized by
texture feature vectors containing the Haralick feature values computed from each directional-GLCM; and the classifier
results obtained were compared to a previously used approach where the directional-GLCMs were summed to a nondirectional
GLCM which could further yield a set of texture feature values. The impact of varying the inter-pixel
distance while generating the GLCMs on the classifier's performance was also investigated. Classifier's AUC was found
to significantly increase when the high-dimensional texture feature vector approach was pursued, and when features
derived from GLCMs generated using different inter-pixel distances were incorporated into the classification task. These
results indicate that lesion character classification accuracy could be improved by retaining the texture features derived
from the different directional GLCMs rather than combining these to yield a set of scalar feature values instead.
Trabecular bone parameters extracted from magnetic resonance (MR) images are compared in their ability to
predict biomechanical properties determined through mechanical testing. Trabecular bone density and structural
changes throughout the proximal tibia are indicative of several musculoskeletal disorders of the knee joint involving
changes in the bone quality and the surrounding soft tissue. Recent studies have shown that MR imaging,
most frequently applied in soft tissue imaging, also allows non-invasive 3-dimensional characterization of bone
microstructure. Sophisticated MR image features that estimate local structural and geometric properties of the
trabecular bone may improve the ability of MR imaging to determine local bone quality in vivo. The purpose
of the current study is to use whole joint MR images to compare the performance of trabecular bone features
extracted from the images in predicting biomechanical strength properties measured on the corresponding ex
vivo specimens. The regional apparent bone volume fraction (appBVF) and scaling index method (SIM) derived
features were calculated; a Multilayer Radial Basis Functions Network was then optimized to calculate the prediction
accuracy as measured by the root mean square error (RSME) for each bone feature. The best prediction
result was obtained with a SIM feature with the lowest prediction error (RSME=0.246) and the highest coefficient
of determination (R2 = 0.769). The current study demonstrates that the combination of sophisticated
bone structure features and supervised learning techniques can improve MR imaging as an in vivo imaging tool
in determining local trabecular bone quality.
Topological texture features were compared in their ability to classify morphological patterns known as 'honeycombing'
that are considered indicative for the presence of fibrotic interstitial lung diseases in high-resolution
computed tomography (HRCT) images. For 14 patients with known occurrence of honey-combing, a stack of 70
axial, lung kernel reconstructed images were acquired from HRCT chest exams. A set of 241 regions of interest
of both healthy and pathological (89) lung tissue were identified by an experienced radiologist. Texture features
were extracted using six properties calculated from gray-level co-occurrence matrices (GLCM), Minkowski Dimensions
(MDs), and three Minkowski Functionals (MFs, e.g. MF.euler). A k-nearest-neighbor (k-NN) classifier
and a Multilayer Radial Basis Functions Network (RBFN) were optimized in a 10-fold cross-validation for each
texture vector, and the classification accuracy was calculated on independent test sets as a quantitative measure
of automated tissue characterization. A Wilcoxon signed-rank test was used to compare two accuracy distributions
and the significance thresholds were adjusted for multiple comparisons by the Bonferroni correction.
The best classification results were obtained by the MF features, which performed significantly better than all
the standard GLCM and MD features (p < 0.005) for both classifiers. The highest accuracy was found for
MF.euler (97.5%, 96.6%; for the k-NN and RBFN classifier, respectively). The best standard texture features
were the GLCM features 'homogeneity' (91.8%, 87.2%) and 'absolute value' (90.2%, 88.5%). The results indicate
that advanced topological texture features can provide superior classification performance in computer-assisted
diagnosis of interstitial lung diseases when compared to standard texture analysis methods.
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