Development and Assessment of Multiple Illumination Color Fourier Ptychographic Microscopy for High Throughput Sample Digitization.

In this study, we proposed a multiplexed color illumination strategy to improve the data acquisition efficiency of Fourier ptychography microscopy (FPM). Instead of sequentially lighting up one single channel LED, our method turns on multiple white light LEDs for each image acquisition via a color camera. Thus, each raw image contains multiplexed spectral information. An FPM prototype was developed, which was equipped with a 4×/0.13 NA objective lens to achieve a spatial resolution equivalent to that of a 20×/0.4 NA objective lens. Both two- and four-LED illumination patterns were designed and applied during the experiments. A USAF 1951 resolution target was first imaged under these illumination conditions, based on which MTF curves were generated to assess the corresponding imaging performance. Next, H&E tissue samples and analyzable metaphase chromosome cells were used to evaluate the clinical utility of our strategy. The results show that the single and multiplexed (two- or four-LED) illumination results achieved comparable imaging performance on all the three channels of the MTF curves. Meanwhile, the reconstructed tissue or cell images successfully retain the definition of cell nuclei and cytoplasm and can better preserve the cell edges as compared to the results from the conventional microscopes. This study initially validates the feasibility of multiplexed color illumination for the future development of high-throughput FPM scanning systems.

Utilizing a Pathomics Biomarker to Predict the Effectiveness of Bevacizumab in Ovarian Cancer Treatment.

The purpose of this investigation is to develop and initially assess a quantitative image analysis scheme that utilizes histopathological images to predict the treatment effectiveness of bevacizumab therapy in ovarian cancer patients. As a widely accessible diagnostic tool, histopathological slides contain copious information regarding underlying tumor progression that is associated with tumor prognosis. However, this information cannot be readily identified by conventional visual examination. This study utilizes novel pathomics technology to quantify this meaningful information for treatment effectiveness prediction. Accordingly, a total of 9828 features were extracted from segmented tumor tissue, cell nuclei, and cell cytoplasm, which were categorized into geometric, intensity, texture, and subcellular structure features. Next, the best performing features were selected as the input for SVM (support vector machine)-based prediction models. These models were evaluated on an open dataset containing a total of 78 patients and 288 whole slides images. The results indicated that the sufficiently optimized, best-performing model yielded an area under the receiver operating characteristic (ROC) curve of 0.8312. When examining the best model's confusion matrix, 37 and 25 cases were correctly predicted as responders and non-responders, respectively, achieving an overall accuracy of 0.7848. This investigation initially validated the feasibility of utilizing pathomics techniques to predict tumor responses to chemotherapy at an early stage.

Developing a novel image marker to predict the clinical outcome of neoadjuvant chemotherapy (NACT) for ovarian cancer patients.

OBJECTIVE: Neoadjuvant chemotherapy (NACT) is one kind of treatment for advanced stage ovarian cancer patients. However, due to the nature of tumor heterogeneity, the clinical outcomes to NACT vary significantly among different subgroups. Partial responses to NACT may lead to suboptimal debulking surgery, which will result in adverse prognosis. To address this clinical challenge, the purpose of this study is to develop a novel image marker to achieve high accuracy prognosis prediction of NACT at an early stage. METHODS: For this purpose, we first computed a total of 1373 radiomics features to quantify the tumor characteristics, which can be grouped into three categories: geometric, intensity, and texture features. Second, all these features were optimized by principal component analysis algorithm to generate a compact and informative feature cluster. This cluster was used as input for developing and optimizing support vector machine (SVM) based classifiers, which indicated the likelihood of receiving suboptimal cytoreduction after the NACT treatment. Two different kernels for SVM algorithm were explored and compared. A total of 42 ovarian cancer cases were retrospectively collected to validate the scheme. A nested leave-one-out cross-validation framework was adopted for model performance assessment. RESULTS: The results demonstrated that the model with a Gaussian radial basis function kernel SVM yielded an AUC (area under the ROC [receiver characteristic operation] curve) of 0.806 ± 0.078. Meanwhile, this model achieved overall accuracy (ACC) of 83.3%, positive predictive value (PPV) of 81.8%, and negative predictive value (NPV) of 83.9%. CONCLUSION: This study provides meaningful information for the development of radiomics based image markers in NACT treatment outcome prediction.

Evaluating the Effectiveness of 2D and 3D CT Image Features for Predicting Tumor Response to Chemotherapy.

Background and Objective: 2D and 3D tumor features are widely used in a variety of medical image analysis tasks. However, for chemotherapy response prediction, the effectiveness between different kinds of 2D and 3D features are not comprehensively assessed, especially in ovarian-cancer-related applications. This investigation aims to accomplish such a comprehensive evaluation. Methods: For this purpose, CT images were collected retrospectively from 188 advanced-stage ovarian cancer patients. All the metastatic tumors that occurred in each patient were segmented and then processed by a set of six filters. Next, three categories of features, namely geometric, density, and texture features, were calculated from both the filtered results and the original segmented tumors, generating a total of 1403 and 1595 features for the 2D and 3D tumors, respectively. In addition to the conventional single-slice 2D and full-volume 3D tumor features, we also computed the incomplete-3D tumor features, which were achieved by sequentially adding one individual CT slice and calculating the corresponding features. Support vector machine (SVM)-based prediction models were developed and optimized for each feature set. Five-fold cross-validation was used to assess the performance of each individual model. Results: The results show that the 2D feature-based model achieved an AUC (area under the ROC curve (receiver operating characteristic)) of 0.84 ± 0.02. When adding more slices, the AUC first increased to reach the maximum and then gradually decreased to 0.86 ± 0.02. The maximum AUC was yielded when adding two adjacent slices, with a value of 0.91 ± 0.01. Conclusions: This initial result provides meaningful information for optimizing machine learning-based decision-making support tools in the future.

Developing a Novel Image Marker to Predict the Responses of Neoadjuvant Chemotherapy (NACT) for Ovarian Cancer Patients.

OBJECTIVE: Neoadjuvant chemotherapy (NACT) is one kind of treatment for advanced stage ovarian cancer patients. However, due to the nature of tumor heterogeneity, the patients' responses to NACT varies significantly among different subgroups. To address this clinical challenge, the purpose of this study is to develop a novel image marker to achieve high accuracy response prediction of the NACT at an early stage. METHODS: For this purpose, we first computed a total of 1373 radiomics features to quantify the tumor characteristics, which can be grouped into three categories: geometric, intensity, and texture features. Second, all these features were optimized by principal component analysis algorithm to generate a compact and informative feature cluster. Using this cluster as the input, an SVM based classifier was developed and optimized to create a final marker, indicating the likelihood of the patient being responsive to the NACT treatment. To validate this scheme, a total of 42 ovarian cancer patients were retrospectively collected. A nested leave-one-out cross-validation was adopted for model performance assessment. RESULTS: The results demonstrate that the new method yielded an AUC (area under the ROC [receiver characteristic operation] curve) of 0.745. Meanwhile, the model achieved overall accuracy of 76.2%, positive predictive value of 70%, and negative predictive value of 78.1%. CONCLUSION: This study provides meaningful information for the development of radiomics based image markers in NACT response prediction.

Using symmetric illumination and color camera to achieve high throughput Fourier ptychographic microscopy.

This study aims to develop a high throughput Fourier ptychographic microscopy (FPM) technique based on symmetric illumination and a color detector, which is able to accelerate image acquisition by up to 12 times. As an emerging technology, the efficiency of FPM is limited by its data acquisition process, especially for color microscope image reconstruction. To overcome this, we built an FPM prototype equipped with a color camera and a 4×/0.13 NA objective lens. During the image acquisition, two symmetric LEDs illuminate the sample simultaneously using white light, which doubles the light intensity and reduces the total captured raw patterns by half. A standard USAF 1951 resolution target was used to measure the system's modulation transfer function (MTF) curve, and the H&E-stained ovarian cancer samples were then imaged to assess the feature qualities depicted on the reconstructed images. The results showed that the measured MTF curves of red, green, and blue channels are generally comparable to the corresponding curves generated by conventional FPM, while symmetric illumination FPM preserves more tissue details, which is superior to the results captured by conventional 20×/0.4 NA objective lens. This investigation initially verified the feasibility of symmetric illumination based color FPM.

Transformers Improve Breast Cancer Diagnosis from Unregistered Multi-View Mammograms.

Deep convolutional neural networks (CNNs) have been widely used in various medical imaging tasks. However, due to the intrinsic locality of convolution operations, CNNs generally cannot model long-range dependencies well, which are important for accurately identifying or mapping corresponding breast lesion features computed from unregistered multiple mammograms. This motivated us to leverage the architecture of Multi-view Vision Transformers to capture long-range relationships of multiple mammograms from the same patient in one examination. For this purpose, we employed local transformer blocks to separately learn patch relationships within four mammograms acquired from two-view (CC/MLO) of two-side (right/left) breasts. The outputs from different views and sides were concatenated and fed into global transformer blocks, to jointly learn patch relationships between four images representing two different views of the left and right breasts. To evaluate the proposed model, we retrospectively assembled a dataset involving 949 sets of mammograms, which included 470 malignant cases and 479 normal or benign cases. We trained and evaluated the model using a five-fold cross-validation method. Without any arduous preprocessing steps (e.g., optimal window cropping, chest wall or pectoral muscle removal, two-view image registration, etc.), our four-image (two-view-two-side) transformer-based model achieves case classification performance with an area under ROC curve (AUC = 0.818 ± 0.039), which significantly outperforms AUC = 0.784 ± 0.016 achieved by the state-of-the-art multi-view CNNs (p = 0.009). It also outperforms two one-view-two-side models that achieve AUC of 0.724 ± 0.013 (CC view) and 0.769 ± 0.036 (MLO view), respectively. The study demonstrates the potential of using transformers to develop high-performing computer-aided diagnosis schemes that combine four mammograms.