X-ray phase tomography with near-field speckles for three-dimensional virtual histology

Abstract

High-contrast, high-resolution imaging of biomedical specimens is indispensable for studying organ function and pathologies. Conventional histology, the gold standard for soft-tissue visualization, is limited by its anisotropic spatial resolution, elaborate sample preparation, and lack of quantitative image information. X-ray absorption or phase tomography have been identified as promising alternatives enabling non-destructive, distortion-free three-dimensional (3D) imaging. However, reaching sufficient contrast and resolution with a simple experimental procedure remains a major challenge. Here, we present a solution based on x-ray phase tomography through speckle-based imaging (SBI). We demonstrate on a mouse kidney that SBI delivers comprehensive 3D maps of hydrated, unstained soft tissue, revealing its microstructure and delivering quantitative tissue-density values at a density resolution of better than <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" display="inline"> <mml:mn>2</mml:mn> <mml:mspace width="thinmathspace"/> <mml:mspace width="thinmathspace"/> <mml:mrow class="MJX-TeXAtom-ORD"> <mml:mi mathvariant="normal">m</mml:mi> <mml:mi mathvariant="normal">g</mml:mi> </mml:mrow> <mml:mrow class="MJX-TeXAtom-ORD"> <mml:mo>/</mml:mo> </mml:mrow> <mml:mrow class="MJX-TeXAtom-ORD"> <mml:msup> <mml:mrow class="MJX-TeXAtom-ORD"> <mml:mi mathvariant="normal">c</mml:mi> <mml:mi mathvariant="normal">m</mml:mi> </mml:mrow> <mml:mrow class="MJX-TeXAtom-ORD"> <mml:mn>3</mml:mn> </mml:mrow> </mml:msup> </mml:mrow> </mml:math> and spatial resolution of better than 8 µm. We expect that SBI virtual histology will find widespread application in biomedicine and will open up new possibilities for research and histopathology.