Signal Recovery Using a Spiked Mixture Model

We introduce the spiked mixture model (SMM) to address the problem of estimating a set of signals from many randomly scaled and noisy observations. Subsequently, we design a novel expectation-maximization (EM) algorithm to recover all parameters of the SMM. Numerical experiments show that in low signal-to-noise ratio regimes, and for data types where the SMM is relevant, SMM surpasses the more traditional Gaussian mixture model (GMM) in terms of signal recovery performance. The broad relevance of the SMM and its corresponding EM recovery algorithm is demonstrated by applying the technique to different data types. The first case study is a biomedical research application, utilizing an imaging mass spectrometry dataset to explore the molecular content of a rat brain tissue section at micrometer scale. The second case study demonstrates SMM performance in a computer vision application, segmenting a hyperspectral imaging dataset into underlying patterns. While the measurement modalities differ substantially, in both case studies SMM is shown to recover signals that were missed by traditional methods such as k-means clustering and GMM.

Virtual Staining of Label-Free Tissue in Imaging Mass Spectrometry

Imaging mass spectrometry (IMS) is a powerful tool for untargeted, highly multiplexed molecular mapping of tissue in biomedical research. IMS offers a means of mapping the spatial distributions of molecular species in biological tissue with unparalleled chemical specificity and sensitivity. However, most IMS platforms are not able to achieve microscopy-level spatial resolution and lack cellular morphological contrast, necessitating subsequent histochemical staining, microscopic imaging and advanced image registration steps to enable molecular distributions to be linked to specific tissue features and cell types. Here, we present a virtual histological staining approach that enhances spatial resolution and digitally introduces cellular morphological contrast into mass spectrometry images of label-free human tissue using a diffusion model. Blind testing on human kidney tissue demonstrated that the virtually stained images of label-free samples closely match their histochemically stained counterparts (with Periodic Acid-Schiff staining), showing high concordance in identifying key renal pathology structures despite utilizing IMS data with 10-fold larger pixel size. Additionally, our approach employs an optimized noise sampling technique during the diffusion model's inference process to reduce variance in the generated images, yielding reliable and repeatable virtual staining. We believe this virtual staining method will significantly expand the applicability of IMS in life sciences and open new avenues for mass spectrometry-based biomedical research.