Fusion of mass spectrometry and microscopy: a multi-modality paradigm for molecular tissue mapping

A new predictive imaging modality is created through the ‘fusion’ of two distinct technologies: imaging mass spectrometry (IMS) and microscopy. IMS-generated molecular maps, rich in chemical information but having coarse spatial resolution, are combined with optical microscopy maps, which have relatively low chemical specificity but high spatial information. The resulting images combine the advantages of both technologies, enabling prediction of a molecular distribution both at high spatial resolution and with high chemical specificity. Multivariate regression is used to model variables in one technology, using variables from the other technology. Several applications demonstrate the remarkable potential of image fusion: (i) ‘sharpening’ of IMS images, which uses microscopy measurements to predict ion distributions at a spatial resolution that exceeds that of measured ion images by ten times or more; (ii) prediction of ion distributions in tissue areas that were not measured by IMS; and (iii) enrichment of biological signals and attenuation of instrumental artifacts, revealing insights that are not easily extracted from either microscopy or IMS separately. Image fusion enables a new multi-modality paradigm for tissue exploration whereby mining relationships between different imaging sensors yields novel imaging modalities that combine and surpass what can be gleaned from the individual technologies alone.