Combined X-ray CT and mass spectrometry for biomedical imaging applications

Imaging technologies play a key role in many branches of science, especially in biology and medicine. They provide an invaluable insight into both internal structure and processes within a broad range of samples. There are many techniques that allow one to obtain images of an object. Different techniques are based on the analysis of a particular sample property by means of a dedicated imaging system, and as such, each imaging modality provides the researcher with different information. The use of multimodal imaging (imaging with several different techniques) can provide additional and complementary information that is not possible when employing a single imaging technique alone.

In this study, we present for the first time a multi-modal imaging technique where X-ray computerized tomography (CT) is combined with mass spectrometry imaging (MSI). While X-ray CT provides 3-dimensional information regarding the internal structure of the sample based on X-ray absorption coefficients, MSI of thin sections acquired from the same sample allows the spatial distribution of many elements/molecules, each distinguished by its unique mass-to-charge ratio (m = z), to be determined within a single measurement and with a spatial resolution as low as 1 m m or even less. The aim of the work is to demonstrate how molecular information from MSI can be spatially correlated with 3D structural information acquired from X-ray CT.

In these experiments, frozen samples are imaged in an X-ray CT setup using Medipix based detectors equipped with a CO2 cooled sample holder. Single projections are pre-processed before tomographic reconstruction using a signal-to-thickness calibration. In the second step, the object is sliced into thin sections (circa 20 mu m) that are then imaged using both matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) and secondary ion (SIMS) mass spectrometry, where the spatial distribution of specific molecules within the sample is determined.

The combination of two vastly different imaging approaches provides complementary information (i.e., anatomical and molecular distributions) that allows the correlation of distinct structural features with specific molecules distributions leading to unique insights in disease development.