Artificial intelligence for breast cancer precision pathology

Breast cancer is the most common cancer type in women globally but is associated with a continuous decline in mortality rates. The improved prognosis can be partially attributed to effective treatments developed for subgroups of patients. However, nowadays, it remains challenging to optimise treatment plans for each individual. To improve disease outcome and to decrease the burden associated with unnecessary treatment and adverse drug effects, the current thesis aimed to develop artificial intelligence based tools to improve individualised medicine for breast cancer patients. In study I, we developed a deep learning based model (DeepGrade) to stratify patients that were associated with intermediate risks. The model was optimised with haematoxylin and eosin (HE) stained whole slide images (WSIs) with grade 1 and 3 tumours and applied to stratify grade 2 tumours into grade 1-like (DG2-low) and grade 3-like (DG2-high) subgroups. The efficacy of the DeepGrade model was validated using recurrence free survival where the dichotomised groups exhibited an adjusted hazard ratio (HR) of 2.94 (95% confidence interval [CI] 1.24-6.97, P = 0.015). The observation was further confirmed in the external test cohort with an adjusted HR of 1.91 (95% CI: 1.11-3.29, P = 0.019). In study II, we investigated whether deep learning models were capable of predicting gene expression levels using the morphological patterns from tumours. We optimised convolutional neural networks (CNNs) to predict mRNA expression for 17,695 genes using HE stained WSIs from the training set. An initial evaluation on the validation set showed that a significant correlation between the RNA-seq measurements and model predictions was observed for 52.75% of the genes. The models were further tested in the internal and external test sets. Besides, we compared the model's efficacy in predicting RNA-seq based proliferation scores. Lastly, the ability of capturing spatial gene expression variations for the optimised CNNs was evaluated and confirmed using spatial transcriptomics profiling. In study III, we investigated the relationship between intra-tumour gene expression heterogeneity and patient survival outcomes. Deep learning models optimised from study II were applied to generate spatial gene expression predictions for the PAM50 gene panel. A set of 11 texture based features and one slide average gene expression feature per gene were extracted as input to train a Cox proportional hazards regression model with elastic net regularisation to predict patient risk of recurrence. Through nested cross-validation, the model dichotomised the training cohort into low and high risk groups with an adjusted HR of 2.1 (95% CI: 1.30-3.30, P = 0.002). The model was further validated on two external cohorts. In study IV, we investigated the agreement between the Stratipath Breast, which is the modified, commercialised DeepGrade model developed in study I, and the Prosigna® test. Both tests sought to stratify patients with distinct prognosis. The outputs from Stratipath Breast comprise a risk score and a two-level risk stratification whereas the outputs from Prosigna® include the risk of recurrence score and a three-tier risk stratification. By comparing the number of patients assigned to ‘low’ or ‘high’ risk groups, we found an overall moderate agreement (76.09%) between the two tests. Besides, the risk scores by two tests also revealed a good correlation (Spearman's rho = 0.59, P = 1.16E-08). In addition, a good correlation was observed between the risk score from each test and the Ki67 index. The comparison was also carried out in the subgroup of patients with grade 2 tumours where similar but slightly dropped correlations were found

Predicting Molecular Phenotypes from Histopathology Images: A Transcriptome-Wide Expression-Morphology Analysis in Breast Cancer

Molecular profiling is central in cancer precision medicine but remains costly and is based on tumor average profiles. Morphologic patterns observable in histopathology sections from tumors are determined by the underlying molecular phenotype and therefore have the potential to be exploited for prediction of molecular phenotypes. We report here the first transcriptome-wide expression-morphology (EMO) analysis in breast cancer, where individual deep convolutional neural networks were optimized and validated for prediction of mRNA expression in 17,695 genes from hematoxylin and eosin-stained whole slide images. Predicted expressions in 9,334 (52.75%) genes were significantly associated with RNA sequencing estimates. We also demonstrated successful prediction of an mRNA-based proliferation score with established clinical value. The results were validated in independent internal and external test datasets. Predicted spatial intratumor variabilities in expression were validated through spatial transcriptomics profiling. These results suggest that EMO provides a cost-efficient and scalable approach to predict both tumor average and intratumor spatial expression from histopathology images.Significance: Transcriptome-wide expression morphology deep learning analysis enables prediction of mRNA expression and proliferation markers from routine histopathology whole slide images in breast cancer

Characteristics of Nd and Sr Isotopes and Trace Elements for late Cretaceous Volcanic Rocks in King George Island, Antarctica: Implications for Source of the Volcanics from Depleted Mantle

Rb-Sr isotropic isochron dating of the volcanic rock samples from the Upper Cretaceous Half Three Point Formation on the King George Island is 71.33 (plus, minus) 0.3Ma

Robust Image Matching Based on Image Feature and Depth Information Fusion

In this paper, we propose a robust image feature extraction and fusion method to effectively fuse image feature and depth information and improve the registration accuracy of RGB-D images. The proposed method directly splices the image feature point descriptors with the corresponding point cloud feature descriptors to obtain the fusion descriptor of the feature points. The fusion feature descriptor is constructed based on the SIFT, SURF, and ORB feature descriptors and the PFH and FPFH point cloud feature descriptors. Furthermore, the registration performance based on fusion features is tested through the RGB-D datasets of YCB and KITTI. ORBPFH reduces the false-matching rate by 4.66~16.66%, and ORBFPFH reduces the false-matching rate by 9~20%. The experimental results show that the RGB-D robust feature extraction and fusion method proposed in this paper is suitable for the fusion of ORB with PFH and FPFH, which can improve feature representation and registration, representing a novel approach for RGB-D image matching

Physics-Based TOF Imaging Simulation for Space Targets Based on Improved Path Tracing

Aiming at the application of close-up space measurement based on time-of-flight (TOF) cameras, according to the analysis of the characteristics of the space background environment and the imaging characteristics of the TOF camera, a physics-based amplitude modulated continuous wave (AMCW) TOF camera imaging simulation method for space targets based on the improved path tracing is proposed. Firstly, the microfacet bidirectional reflection distribution function (BRDF) model of several typical space target surface materials is fitted according to the measured BRDF data in the TOF camera response band to make it physics-based. Secondly, an improved path tracing algorithm is developed to adapt to the TOF camera by introducing a cosine component to characterize the modulated light in the TOF camera. Then, the imaging link simulation model considering the coupling effects of the BRDF of materials, the suppression of background illumination (SBI), optical system, detector, electronic equipment, platform vibration, and noise is established, and the simulation images of the TOF camera are obtained. Finally, ground tests are carried out, and the test shows that the relative error of the grey mean, grey variance, depth mean, and depth variance is 2.59%, 3.80%, 18.29%, and 14.58%, respectively; the MSE, SSIM, and PSNR results of our method are also better than those of the reference method. The ground test results verify the correctness of the proposed simulation model, which can provide image data support for the ground test of TOF camera algorithms for space targets

Binary Feature Description of 3D Point Cloud Based on Retina-like Sampling on Projection Planes

A binary feature description and registration algorithm for a 3D point cloud based on retina-like sampling on projection planes (RSPP) are proposed in this paper. The algorithm first projects the point cloud within the support radius around the key point to the XY, YZ, and XZ planes of the Local Reference Frame (LRF) and performs retina-like sampling on the projection plane. Then, the binarized Gaussian density weight values at the sampling points are calculated and encoded to obtain the RSPP descriptor. Finally, rough registration of point clouds is performed based on the RSPP descriptor, and the RANSAC algorithm is used to optimize the registration results. The performance of the proposed algorithm is tested on public point cloud datasets. The test results show that the RSPP-based point cloud registration algorithm has a good registration effect under no noise, 0.25 mr, and 0.5 mr Gaussian noise. The experimental results verify the correctness and robustness of the proposed registration method, which can provide theoretical and technical support for the 3D point cloud registration application

Space-Based THz Radar Fly-Around Imaging Simulation for Space Targets Based on Improved Path Tracing

Aiming at the space target detection application of a space-based terahertz (THz) radar, according to the imaging mechanism of broadband THz radars, a THz radar imaging simulation method based on improved path tracing is proposed. Firstly, the characterization method of THz scattering characteristics based on Kirchhoff’s approximation method is introduced. The multi-parameter THz bidirectional reflectance distribution function (THz-BRDF) models of aluminum (Al), white-painted Al, and polyimide film at 0.215 THz are fitted according to the theoretical data, with fitting errors below 4%. Then, the THz radar imaging simulation method based on improved path tracing is presented in detail. The simulation method utilizes path tracing to simulate parallelized THz radar echo signal data, considering multi-path energy scattering based on the THz-BRDF model. Finally, we conducted THz radar imaging simulation experiments. The influences in the imaging process of different fly-around motions are analyzed, and a comparison experiment is conducted with the fast-physical optics (FPO) method. The comparative results indicate that the proposed method exhibits richer and more realistic features compared with the FPO method. The simulation experiments results demonstrate that the proposed method can provide a data source for ground algorithm testing of THz radars, particularly in evaluating the target detection and recognition algorithm based on deep learning, providing strong support for the application of space-based THz radars in the future

Physics-Based TOF Imaging Simulation for Space Targets Based on Improved Path Tracing

Aiming at the application of close-up space measurement based on time-of-flight (TOF) cameras, according to the analysis of the characteristics of the space background environment and the imaging characteristics of the TOF camera, a physics-based amplitude modulated continuous wave (AMCW) TOF camera imaging simulation method for space targets based on the improved path tracing is proposed. Firstly, the microfacet bidirectional reflection distribution function (BRDF) model of several typical space target surface materials is fitted according to the measured BRDF data in the TOF camera response band to make it physics-based. Secondly, an improved path tracing algorithm is developed to adapt to the TOF camera by introducing a cosine component to characterize the modulated light in the TOF camera. Then, the imaging link simulation model considering the coupling effects of the BRDF of materials, the suppression of background illumination (SBI), optical system, detector, electronic equipment, platform vibration, and noise is established, and the simulation images of the TOF camera are obtained. Finally, ground tests are carried out, and the test shows that the relative error of the grey mean, grey variance, depth mean, and depth variance is 2.59%, 3.80%, 18.29%, and 14.58%, respectively; the MSE, SSIM, and PSNR results of our method are also better than those of the reference method. The ground test results verify the correctness of the proposed simulation model, which can provide image data support for the ground test of TOF camera algorithms for space targets

Geochemistry of eolian dust and its elemental contribution to Lake Qinghai sediment

Located at the midpoint of the Asian &quot;airborne dust corridor&#39;&#39;, Lake Qinghai receives substantial dust annually, which may impact the biogeochemical cycles of the system. In order to determine quantitatively the flux and chemical contributions of dust to Lake Qinghai sediment, dust samples were collected monthly at two sites surrounding the lake from June 2009 to May 2011. The results demonstrate similar chemical compositions of dust samples to the local loess, implying strong representativeness of regional dust. The average dust deposition flux is 265.7 +/- 55.0 g/m(2)/a, constituting 56.6 +/- 11.7% of the modern sediment, approximating to previous estimates (similar to 65%). Contributions of dust-derived elements in the sediment differ substantially, with a minimum of 16.7% for Sr and a maximum of 83.9% for Cu. Among these elements, the contribution of lithophile elements (Na, Al, K, Ti, Mn, Fe and Rb) is close to that of the bulk dust; the contributions of mobile elements (Mg, Ca and Sr) are low, only 16.7% (Sr)-26.1% (Mg), whereas potentially harmful metals (Cu, Zn and Pb) have high contributions (70.3-83.9%). Seasonal variations of elemental inputs indicate that springtime contributions dominate the annual dust fluxes for all elements into the sediment, in agreement with the high dust flux in spring. These observations not only quantify the contribution of dust to the sediment of Lake Qinghai, but also highlight the important role of dust in the accumulation of various elements in the sediment, especially for potentially harmful metals.</p

Transcriptional intra-tumour heterogeneity predicted by deep learning in routine breast histopathology slides provides independent prognostic information

Background: Intra-tumour heterogeneity (ITH) causes diagnostic challenges and increases the risk for disease recurrence. Quantification of ITH is challenging and has not been demonstrated in large studies. It has previously been shown that deep learning can enable spatially resolved prediction of molecular phenotypes from digital histopathology whole slide images (WSIs). Here we propose a novel method (Deep-ITH) to predict and measure ITH, and we evaluate its prognostic performance in breast cancer. Methods: Deep convolutional neural networks were used to spatially predict gene-expression (PAM50 set) from WSIs. For each predicted transcript, 12 measures of heterogeneity were extracted in the training data set (N = 931). A prognostic score to dichotomise patients into Deep-ITH low- and high-risk groups was established using an elastic-net regularised Cox proportional hazards model (recurrence-free survival). Prognostic performance was evaluated in two independent data sets: SöS-BC-1 (N = 1358) and SCAN-B-Lund (N = 1262). Results: We observed an increase in risk of recurrence in the high-risk group with hazard ratio (HR) 2.11 (95%CI:1.22–3.60; p = 0.007) using nested cross-validation. Subgroup analyses confirmed the prognostic performance in oestrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative, grade 3, and large tumour subgroups. The prognostic value was confirmed in the independent SöS-BC-1 cohort (HR = 1.84; 95%CI:1.03–3.3; p = 3.99 × 10−2). In the other external cohort, significant HR was observed in the subgroup of histological grade 2 patients, as well as in the subgroup of patients with small tumours (<20 mm). Conclusion: We developed a novel method for an automated, scalable, and cost-efficient measure of ITH from WSIs that provides independent prognostic value for breast cancer. Significance: Transcriptional ITH predicted by deep learning models enables prediction of patient survival from routine histopathology WSIs in breast cancer