Spatial distribution of tumor infiltrating lymphocytes (TILs) and cancer cells in the tumor microenvironment (TME) along with tumor gene mutation status are of vital importance to the guidance of cancer immunotherapy and prognoses. In this work, we developed a deep learning-based computational framework, termed ImmunoAIzer, which involves: (1) the implementation of a semi-supervised strategy to train a cellular biomarker distribution prediction network (CBDPN) to make predictions of spatial distributions of CD3, CD20, PanCK, and DAPI biomarkers in the tumor microenvironment with an accuracy of 90.4%; (2) using CBDPN to select tumor areas on hematoxylin and eosin (H&E) staining tissue slides and training a multilabel tumor gene mutation detection network (TGMDN), which can detect APC, KRAS, and TP53 mutations with area-under-the-curve (AUC) values of 0.76, 0.77, and 0.79. These findings suggest that ImmunoAIzer could provide comprehensive information of cell distribution and tumor gene mutation status of colon cancer patients efficiently and less costly; hence, it could serve as an effective auxiliary tool for the guidance of immunotherapy and prognoses. The method is also generalizable and has the potential to be extended for application to other types of cancers other than colon cancer.

Fluorescence molecular tomography (FMT) is a new type of medical imaging technology that can quantitatively reconstruct the three-dimensional distribution of fluorescent probes in vivo. Traditional Lp norm regularization techniques used in FMT reconstruction often face problems such as over-sparseness, over-smoothness, spatial discontinuity, and poor robustness. To address these problems, this paper proposes an adaptive parameter search elastic net (APSEN) method that is based on elastic net regularization, using weight parameters to combine the L1 and L2 norms. For the selection of elastic net weight parameters, this approach introduces the L0 norm of valid reconstruction results and the L2 norm of the residual vector, which are used to adjust the weight parameters adaptively. To verify the proposed method, a series of numerical simulation experiments were performed using digital mice with tumors as experimental subjects, and in vivo experiments of liver tumors were also conducted. The results showed that, compared with the state-of-the-art methods with different light source sizes or distances, Gaussian noise of 5%-25%, and the brute-force parameter search method, the APSEN method has better location accuracy, spatial resolution, fluorescence yield recovery ability, morphological characteristics, and robustness. Furthermore, the in vivo experiments demonstrated the applicability of APSEN for FMT.

The traditional finite element method-based fluorescence molecular tomography (FMT)/ X-ray computed tomography (XCT) imaging reconstruction suffers from complicated mesh generation and dual-modality image data fusion, which limits the application of in vivo imaging. To solve this problem, a novel standardized imaging space reconstruction (SISR) method for the quantitative determination of fluorescent probe distributions inside small animals was developed. In conjunction with a standardized dual-modality image data fusion technology, and novel reconstruction strategy based on Laplace regularization and L1-fused Lasso method, the in vivo distribution can be calculated rapidly and accurately, which enables standardized and algorithm-driven data process. We demonstrated the method’s feasibility through numerical simulations and quantitatively monitored in vivo programmed death ligand 1 (PD-L1) expression in mouse tumor xenografts, and the results demonstrate that our proposed SISR can increase data throughput and reproducibility, which helps to realize the dynamically and accurately in vivo imaging.

In this study, the prognostic value of cellular morphology and spatial configurations in melanoma has been examined, aiming to complement traditional prognostic indicators like mitotic activity and tumor thickness. Through a computational pipeline using machine learning and deep learning methods, we quantified nuclei sizes within different spatial regions and analyzed their prognostic significance using univariate and multivariate Cox models. Nuclei sizes in the invasive band demonstrated a significant hazard ratio (HR) of 1.1 (95% CI: 1.03, 1.18). Similarly, the nuclei sizes of tumor cells and Ki67 S100 co-positive cells in the invasive band achieved HRs of 1.07 (95% CI: 1.02, 1.13) and 1.09 (95% CI: 1.04, 1.16), respectively. Our findings reveal that nuclei sizes, particularly in the invasive band, are potentially prognostic factors. Correlation analyses further demonstrated a meaningful relationship between cellular morphology and tumor progression, notably showing that nuclei size within the invasive band correlates substantially with tumor thickness. These results suggest the potential of integrating spatial and morphological analyses into melanoma prognostication.