Biomedical Engineering

Heterogeneity in cardiac tissue microstructure is a potential mechanism for the generation and maintenance of arrhythmias. Abnormal changes in fiber orientation increase the likelihood of arrhythmia. We present optical coherence tomography (OCT) as a method to image myofibers in excised intact heart preparations. Three-dimensional (3-D) image sets were gathered from the rabbit right ventricular free wall (RVFW) using a microscope-integrated OCT system. An automated algorithm for fiber orientation quantification in the plane parallel to the wall surface was developed. The algorithm was validated by comparison with manual measurements. Quantifying fiber orientation in the plane parallel to the wall surface from OCT images can be used to help understand the conduction system of the specific sample being imaged.

With a wide array of multi-modal, multi-protocol, and multi-scale biomedical data available for disease diagnosis and prognosis, there is a need for quantitative tools to combine such varied channels of information, especially imaging and non-imaging data (e.g. spectroscopy, proteomics). The major problem in such quantitative data integration lies in reconciling the large spread in the range of dimensionalities and scales across the different modalities. The primary goal of quantitative data integration is to build combined meta-classifiers; however these efforts are thwarted by challenges in (1) homogeneous representation of the data channels, (2) fusing the attributes to construct an integrated feature vector, and (3) the choice of learning strategy for training the integrated classifier. In this paper, we seek to (a) define the characteristics that guide the 4 independent methods for quantitative data fusion that use the idea of a meta-space for building integrated multi-modal, multi-scale meta-classifiers, and (b) attempt to understand the key components which allowed each method to succeed. These methods include (1) Generalized Embedding Concatenation (GEC), (2) Consensus Embedding (CE), (3) Semi-Supervised Multi-Kernel Graph Embedding (SeSMiK), and (4) Boosted Embedding Combination (BEC). In order to evaluate the optimal scheme for fusing imaging and nonimaging data, we compared these 4 schemes for the problems of combining (a) multi-parametric MRI with spectroscopy for prostate cancer (CaP) diagnosis in vivo, and (b) histological image with proteomic signatures (obtained via mass spectrometry) for predicting prognosis in CaP patients. The kernel combination approach (SeSMiK) marginally outperformed the embedding combination schemes. Additionally, intelligent weighting of the data channels (based on their relative importance) appeared to outperform unweighted strategies. All 4 strategies easily outperformed a naïve decision fusion approach, suggesting that data integration methods will play an important role in the rapidly emerging field of integrated diagnostics and personalized healthcare.

Recently, both Magnetic Resonance (MR) Imaging (MRI) and Spectroscopy (MRS) have emerged as promising tools for detection of prostate cancer (CaP). However, due to the inherent dimensionality differences in MR imaging and spectral information, quantitative integration of T 2 weighted MRI (T 2 w MRI) and MRS for improved CaP detection has been a major challenge. In this paper, we present a novel computerized decision support system called multimodal wavelet embedding representation for data combination (MaWERiC) that employs, (i) wavelet theory to extract 171 Haar wavelet features from MRS and 54 Gabor features from T 2 w MRI, (ii) dimensionality reduction to individually project wavelet features from MRS and T 2 w MRI into a common reduced Eigen vector space, and (iii), a random forest classifier for automated prostate cancer detection on a per voxel basis from combined 1.5 T in vivo MRI and MRS. A total of 36 1.5 T endorectal in vivo T 2 w MRI and MRS patient studies were evaluated per voxel by MaWERiC using a three-fold cross validation approach over 25 iterations. Ground truth for evaluation of results was obtained by an expert radiologist annotations of prostate cancer on a per voxel basis who compared each MRI section with corresponding ex vivo wholemount histology sections with the disease extent mapped out on histology. Results suggest that MaWERiC based MRS T 2 w meta-classifier (mean AUC, m = 0.89 AE 0.02) significantly outperformed (i) a T 2 w MRI (using wavelet texture features) classifier (m = 0.55 AE 0.02), (ii) a MRS (using metabolite ratios) classifier (m = 0.77 AE 0.03), (iii) a decision fusion classifier obtained by combining individual T 2 w MRI and MRS classifier outputs (m = 0.85 AE 0.03), and (iv) a data combination method involving a combination of metabolic MRS and MR signal intensity features (m = 0.66 AE 0.02).

Even though 1 in 6 men in the US, in their lifetime are expected to be diagnosed with prostate cancer (CaP), only 1 in 37 is expected to die on account of it. Consequently, among many men diagnosed with CaP, there has been a recent trend to resort to active surveillance (wait and watch) if diagnosed with a lower Gleason score on biopsy, as opposed to seeking immediate treatment. Some researchers have recently identified imaging markers for low and high grade CaP on multi-parametric (MP) magnetic resonance (MR) imaging (such as T2 weighted MR imaging (T2w MRI) and MR spectroscopy (MRS)). In this paper, we present a novel computerized decision support system (DSS), called Semi Supervised Multi Kernel Graph Embedding (SeSMiK-GE), that quantitatively combines structural, and metabolic imaging data for distinguishing (a) benign versus cancerous, and (b) high-versus low-Gleason grade CaP regions from in vivo MP-MRI. A total of 29 1.5 Tesla endorectal pre-operative in vivo MP MRI (T2w MRI, MRS) studies from patients undergoing radical prostatectomy were considered in this study. Ground truth for evaluation of the SeSMiK-GE classifier was obtained via annotation of disease extent on the preoperative imaging by visually correlating the MRI to the ex vivo whole mount histologic specimens. The SeSMiK-GE framework comprises of three main modules: (1) multi-kernel learning, (2) semi-supervised learning, and (3) dimensionality reduction, which are leveraged for the construction of an integrated low dimensional representation of the different imaging and non-imaging MRI protocols. Hierarchical classifiers for diagnosis and Gleason grading of CaP are then constructed within this unified low dimensional representation.

Segmentation of the prostate boundary on clinical images is useful in a large number of applications including calculating prostate volume during biopsy, tumor estimation, and treatment planning. Manual segmentation of the prostate boundary is, however, time consuming and subject to inter-and intra-reader variability. Magnetic Resonance (MR) imaging (MRI) and MR Spectroscopy (MRS) have recently emerged as promising modalities for detection of prostate cancer in vivo. In this paper we present a novel scheme for accurate and automated prostate segmentation on in vivo 1.5 Tesla multi-modal MRI studies. The segmentation algorithm comprises two steps: (1) A hierarchical unsupervised spectral clustering scheme using MRS data to isolate the region of interest (ROI) corresponding to the prostate, and an Active Shape Model (ASM) segmentation scheme where the ASM is initialized within the ROI obtained in the previous step. The hierarchical MRS clustering scheme in step 1 identifies spectra corresponding to locations within the prostate in an iterative fashion by discriminating between potential prostate and non-prostate spectra in a lower dimensional embedding space. The spatial locations of the prostate spectra so identified are used as the initial ROI for the ASM. The ASM is trained by identifying user-selected landmarks on the prostate boundary on T2 MRI images. Boundary points on the prostate are identified using mutual information (MI) as opposed to the traditional Mahalanobis distance, and the trained ASM is deformed to fit the boundary points so identified. Cross validation on 150 prostate MRI slices yields an average segmentation sensitivity, specificity, overlap, and positive predictive value of 89%, 86%, 83%, and 93% respectively. We demonstrate that the accurate initialization of the ASM via the spectral clustering scheme is necessary for automated boundary extraction. Our method is fully automated, robust to system parameters, and computationally efficient.

Segmentation of the prostate boundary on clinical images is useful in a large number of applications including calculation of prostate volume pre-and post-treatment, to detect extra-capsular spread, and for creating patient-specific anatomical models. Manual segmentation of the prostate boundary is, however, time consuming and subject to inter-and intra-reader variability. T2-weighted (T2-w) magnetic resonance (MR) structural imaging (MRI) and MR spectroscopy (MRS) have recently emerged as promising modalities for detection of prostate cancer in vivo. MRS data consists of spectral signals measuring relative metabolic concentrations, and the metavoxels near the prostate have distinct spectral signals from metavoxels outside the prostate. Active Shape Models (ASM's) have become very popular segmentation methods for biomedical imagery. However, ASMs require careful initialization and are extremely sensitive to model initialization. The primary contribution of this paper is a scheme to automatically initialize an ASM for prostate segmentation on endorectal in vivo multi-protocol MRI via automated identification of MR spectra that lie within the prostate. A replicated clustering scheme is employed to distinguish prostatic from extra-prostatic MR spectra in the midgland. The spatial locations of the prostate spectra so identified are used as the initial ROI for a 2D ASM. The midgland initializations are used to define a ROI that is then scaled in 3D to cover the base and apex of the prostate. A multi-feature ASM employing statistical texture features is then used to drive the edge detection instead of just image intensity information alone. Quantitative comparison with another recent ASM initialization method by Cosio showed that our scheme resulted in a superior average segmentation performance on a total of 388 2D MRI sections obtained from 32 3D endorectal in vivo patient studies. Initialization of a 2D ASM via our MRS-based clustering scheme resulted in an average overlap accuracy (true positive ratio) of 0.60, while the scheme of Cosio yielded a corresponding average accuracy of 0.56 over 388 2D MR image sections. During an ASM segmentation, using no initialization resulted in an overlap of 0.53, using the Cosio based methodology resulted in an overlap of 0.60, and using the MRS-based methodology resulted in an overlap of 0.67, with a paired Student's t-test indicating statistical significance to a high degree for all results. We also show that the final ASM segmentation result is highly correlated (as high as 0.90) to the initialization scheme.

Magnetic resonance spectroscopy ͑MRS͒ has been shown to have great clinical potential as a supplement to magnetic resonance imaging in the detection of prostate cancer ͑CaP͒. MRS provides functional information in the form of changes in the relative concentration of specific metabolites including choline, creatine, and citrate which can be used to identify potential areas of CaP. With a view to assisting radiologists in interpretation and analysis of MRS data, some researchers have begun to develop computer-aided detection ͑CAD͒ schemes for CaP identification from spectroscopy. Most of these schemes have been centered on identifying and integrating the area under metabolite peaks which is then used to compute relative metabolite ratios. However, manual identification of metabolite peaks on the MR spectra, and especially via CAD, is a challenging problem due to low signal-to-noise ratio, baseline irregularity, peak overlap, and peak distortion. In this article the authors present a novel CAD scheme that integrates nonlinear dimensionality reduction ͑NLDR͒ with an unsupervised hierarchical clustering algorithm to automatically identify suspicious regions on the prostate using MRS and hence avoids the need to explicitly identify metabolite peaks. The methodology comprises two stages. In stage 1, a hierarchical spectral clustering algorithm is used to distinguish between extracapsular and prostatic spectra in order to localize the region of interest ͑ROI͒ corresponding to the prostate. Once the prostate ROI is localized, in stage 2, a NLDR scheme, in conjunction with a replicated clustering algorithm, is used to automatically discriminate between three classes of spectra ͑normal appearing, suspicious appearing, and inde-terminate͒. The methodology was quantitatively and qualitatively evaluated on a total of 18 1.5 T in vivo prostate T2-weighted ͑w͒ and MRS studies obtained from the multisite, multi-institutional American College of Radiology ͑ACRIN͒ trial. In the absence of the precise ground truth for CaP extent on the MR imaging for most of the ACRIN studies, probabilistic quantitative metrics were defined based on partial knowledge on the quadrant location and size of the tumor. The scheme, when evaluated against this partial ground truth, was found to have a CaP detection sensitivity of 89.33% and specificity of 79.79%. The results obtained from randomized threefold and fivefold cross validation suggest that the NLDR based clustering scheme has a higher CaP detection accuracy compared to such commonly used MRS analysis schemes as z score and PCA. In addition, the scheme was found to be robust to changes in system parameters. For 6 of the 18 studies an expert radiologist laboriously labeled each of the individual spectra according to a five point scale, with 1 / 2 representing spectra that the expert considered normal and 3 / 4 / 5 being spectra the expert deemed suspicious. When evaluated on these expert annotated datasets, the CAD system yielded an average sensitivity ͑cluster corresponding to suspicious spectra being identified as the CaP class͒ and specificity of 81.39% and 64.71%, respectively.