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Register a new userAdvanced machine learning informatics modeling using clinical and radiological imaging metrics for characterizing breast tumor characteristics with the OncotypeDX gene array
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Purpose-Optimal use of established and imaging methods, such as multiparametric magnetic resonance imaging(mpMRI) can simultaneously identify key functional parameters and provide unique imaging phenotypes of breast cancer. Therefore, we have developed and implemented a new machine-learning informatic system that integrates clinical variables, derived from imaging and clinical health records, to compare with the 21-gene array assay, OncotypeDX. Materials and methods-We tested our informatics modeling in a subset of patients (n=81) who had ER+ disease and underwent OncotypeDX gene expression and breast mpMRI testing. The machine-learning informatic method is termed Integrated Radiomic Informatic System-IRIS was applied to the mpMRI, clinical and pathologic descriptors, as well as a gene array analysis. The IRIS method using an advanced graph theoretic model and quantitative metrics. Summary statistics (mean and standard deviations) for the quantitative imaging parameters were obtained. Sensitivity and specificity and Area Under the Curve were calculated for the classification of the patients. Results-The OncotypeDX classification by IRIS model had sensitivity of 95% and specificity of 89% with AUC of 0.92. The breast lesion size was larger for the high-risk groups and lower for both low risk and intermediate risk groups. There were significant differences in PK-DCE and ADC map values in each group. The ADC map values for high- and intermediate-risk groups were significantly lower than the low-risk group. Conclusion-These initial studies provide deeper understandings of imaging features and molecular gene array OncotypeDX score. This insight provides the foundation to relate these imaging features to the assessment of treatment response for improved personalized medicine.
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Simulation-based image quality metrics are adapted and investigated for characterizing the parameter dependences of linear iterative image reconstruction for DBT. Three metrics based on 2D DBT simulation are investigated: (1) a root-mean-square-error (RMSE) between the test phantom and reconstructed image, (2) a gradient RMSE where the comparison is made after taking a spatial gradient of both image and phantom, and (3) a region-of-interest (ROI) Hotelling observer (HO) for signal-known-exactly/background-known-exactly (SKE/BKE) and signal-known-exactly/background-known-statistically (SKE/BKS) detection tasks. Two simulation studies are performed using the aforementioned metrics, varying voxel aspect ratio and regularization strength for two types of Tikhonov regularized least-squares optimization. The RMSE metrics are applied to a 2D test phantom and the ROI-HO metric is applied to two tasks relevant to DBT: large, low contrast lesion detection and small, high contrast microcalcification detection. The RMSE metric trends are compared with visual assessment of the reconstructed test phantom. The ROI-HO metric trends are compared with 3D reconstructed images from ACR phantom data acquired with a Hologic Selenia Dimensions DBT system. Sensitivity of image RMSE to mean pixel value is found to limit its applicability to the assessment of DBT image reconstruction. Image gradient RMSE is insensitive to mean pixel value and appears to track better with subjective visualization of the reconstructed bar-pattern phantom. The ROI-HO metric shows an increasing trend with regularization strength for both forms of Tikhonov-regularized least-squares; however, this metric saturates at intermediate regularization strength indicating a point of diminishing returns for signal detection. Visualization with reconstructed ACR phantom images appears to show a similar dependence with regularization strength.
Solute transport is modeled using mixture theory, applied to the nanoparticle accumulation and concentration decay in the tissue space for different vascular configurations. A comparison of a single capillary configuration (SBC) with two parallel cylindrical blood vessels (2 BC) and a lymph vessel parallel to a blood vessel (BC_LC) embedded in the tissue cylinder is performed for five solute molecular weights between 0.1 kDa and 70 kDa. We found that the presence of a second capillary reduces the extravascular concentration compared to a single capillary and this reduction is enhanced by the presence of a lymph vessel. Co-current flow direction between two adjacent vessels led to nonhomogeneous nanoparticle distribution for larger particle sizes in the tissue space, while smaller particles (0.1 kDa and 3 kDa) showed the propensity to get trapped locally in the tissue during counter-current flow. Varying the intercapillary distance with respect to vessel diameter shows a deviation of 10-30 % concentration for 2 BC and 45-60% concentration for BC_LC configuration compared to the reference SBC configuration. Finally, we introduce a non-dimensional time scale that captures the concertation as a function of the transport and geometric parameters. We find that the peak solute concentration in the tissue space occurs at a non-dimensional time, T_peak^* = 0.027+/-0.018, irrespective of the solute size, tissue architecture, and microvessel flow direction. This suggests that if indeed such a universal time scale holds, the knowledge of this time would allow estimation of the time window at which solute concentration in tissue peaks. Hence this can aid in the design of future therapeutic efficacy studies as an example for triggering drug release or laser excitation in the case of photothermal therapies.
Measurements of breast density have the potential to improve the efficiency and reduce the cost of screening mammography through personalized screening. Breast density has traditionally been evaluated from the dense area in a mammogram, but volumetric assessment methods, which measure the volumetric fraction of fibro-glandular tissue in the breast, are potentially more consistent and physically sound. The purpose of the present study is to evaluate a method for measuring the volumetric breast density using photon-counting spectral tomosynthesis. The performance of the method was evaluated using phantom measurements and clinical data from a small population (n=18). The precision was determined to 2.4 percentage points (pp) of volumetric breast density. Strong correlations were observed between contralateral (R^2=0.95) and ipsilateral (R^2=0.96) breast-density measurements. The measured breast density was anti-correlated to breast thickness, as expected, and exhibited a skewed distribution in the range [3.7%, 55%] and with a median of 18%. We conclude that the method yields promising results that are consistent with expectations. The relatively high precision of the method may enable novel applications such as treatment monitoring.
Tumor segmentation in oncological PET is challenging, a major reason being the partial-volume effects due to the low system resolution and finite voxel size. The latter results in tissue-fraction effects, i.e. voxels contain a mixture of tissue classes. Most conventional methods perform segmentation by exclusively assigning each voxel in the image as belonging to either the tumor or normal tissue classes. Thus, these methods are inherently limited in modeling the tissue-fraction effects. To address this inherent limitation, we propose an estimation-based approach to segmentation. Specifically, we develop a Bayesian method that estimates the posterior mean of fractional volume that the tumor occupies within each image voxel. The proposed method, implemented using an encoder-decoder network, was first evaluated using clinically realistic 2-D simulation studies with known ground truth, in the context of segmenting the primary tumor in PET images of patients with lung cancer. The evaluation studies demonstrated that the method accurately estimated the tumor-fraction areas and significantly outperformed widely used conventional methods, including a U-net-based method, on the task of segmenting the tumor. In addition, the proposed method was relatively insensitive to partial-volume effects and yielded reliable tumor segmentation for different clinical-scanner configurations. The method was then evaluated using clinical images of patients with stage II and III non-small cell lung cancer from ACRIN 6668/RTOG 0235 multi-center clinical trial. Here, the results showed that the proposed method significantly outperformed all other considered methods and yielded accurate tumor segmentation on patient images with dice similarity coefficient of 0.82 (95% CI: 0.78, 0.86). Overall, this study demonstrates the efficacy of the proposed method to accurately segment tumors in PET images.
The human-associated microbiome is closely tied to human health and is of substantial clinical interest. Metagenomics-based tools are emerging for clinical diagnostics, tracking the spread of diseases, and surveillance of potential pathogens. In some cases, these tools are overcoming limitations of traditional clinical approaches. Metagenomics has limitations barring the tools from clinical validation. Once these hurdles are overcome, clinical metagenomics will inform doctors of the best, targeted treatment for their patients and provide early detection of disease. Here we present an overview of metagenomics methods with a discussion of computational challenges and limitations.
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