SUMMARY: Joint analysis of mass spectrometry images (MS images) and microscopy images of hematoxylin and eosin (H&E) stained tissues assists pathologists in characterizing the morphological structure of the tissues, and in performing diagnosis. Unfortunately, the analysis is undermined by substantial differences between these modalities in terms of aspect ratios, spatial resolution, number of channels in each image, as well as by large global or small local elastic spatial deformations of one image with respect to the other. Therefore, accurate coregistration of the images is a critical pre-requisite for their joint interpretation. We introduce MSIreg, an open-source R package for coregistration of MSI and H&E images. MSIreg is designed for high-dimensional MSI experiments where each spatial location is represented by thousands of mass features. Unlike most existing coregistration methods, MSIreg implements a landmark free workflow, and quantitative metrics for performance evaluation. We evaluate the performance of MSIreg on six case studies, including coregistration of contiguous tissues with large deformations, as well as simultaneous coregistration of 29 tissue microarray cores. AVAILABILITY AND IMPLEMENTATION: The R package, installation instructions, and fully reproducible vignettes describing methods and Case Studies are available open-source under the GPL-3.0 license at https://github.com/sslakkimsetty/msireg/.

MOTIVATION: Mass spectrometry imaging (MSI) characterizes the molecular composition of tissues at spatial resolution, and has a strong potential for distinguishing tissue types, or disease states. This can be achieved by supervised classification, which takes as input MSI spectra, and assigns class labels to subtissue locations. Unfortunately, developing such classifiers is hindered by the limited availability of training sets with subtissue labels as the ground truth. Subtissue labeling is prohibitively expensive, and only rough annotations of the entire tissues are typically available. Classifiers trained on data with approximate labels have sub-optimal performance. RESULTS: To alleviate this challenge, we contribute a semi-supervised approach mi-CNN. mi-CNN implements multiple instance learning with a convolutional neural network (CNN). The multiple instance aspect enables weak supervision from tissue-level annotations when classifying subtissue locations. The convolutional architecture of the CNN captures contextual dependencies between the spectral features. Evaluations on simulated and experimental datasets demonstrated that mi-CNN improved the subtissue classification as compared to traditional classifiers. We propose mi-CNN as an important step toward accurate subtissue classification in MSI, enabling rapid distinction between tissue types and disease states. AVAILABILITY AND IMPLEMENTATION: The data and code are available at https://github.com/Vitek-Lab/mi-CNN_MSI.

The objectives of this work are (1) to develop a classifier application for tumor staging based on a formal representation of the Tumor-Node-Metastasis classification system (TNM), and (2) to show the feasibility of this approach on real data. This paper presents a classifier application for colorectal tumors based on the TNM-O ontology. It was developed in the JAVA using the OWL-API. The TNM-O uses the Foundational Model of Anatomy for representing anatomical entities and BioTopLite2 as a domain-top-level ontology. The classifier application processes input data via a user interface or tabular data. The classification starts with the creation of RDF Individuals for each pathological information item formally described in the ontology. These Individuals are then classified by the HermiT Description Logics reasoner by A-Box classification. A dataset with 382 entries was provided by the pathology department of a university hospital. It was automatically classified with regard to metastatic regional lymph nodes. Results or expert classification by pathologists and automatic classification were compared. The automatic process helped to detect and explain inconsistencies between expert and automatic classifications. This work, we demonstrate the use of semantic technologies in a TNM classifier application separating underlying medical knowledge represented in OWL from process logics. The presented prototypical TNM classifier application shows the potential to be integrated in larger software systems.