Imaging the Human Body Down to the Molecular Level
KeywordsGray Matter Fringe Pattern Insertion Device Clinical Compute Tomography Tooth Hard Tissue
The human body consists of nanometer-sized units including proteins, apatite crystallites, collagen, and myelin fibers. Imaging, here, means the identification, localization, and quantification of these units within the human body.
Three-dimensional (3D) imaging in daily clinical practice of well-equipped hospitals reaches a spatial resolution of a fraction of a millimeter, as indicated by the magnetic resonance imaging (MRI) in Fig. 1. Hence, the spatial resolution of medical imaging facilities is far from the molecular scale. In engineering and research, however, methods are known that allow imaging structures down to the world of atoms. As shown in the overview of Fig. 1, micro-computed tomography (μCT) is well established in materials science and yields a spatial resolution as low as a fraction of a micrometer in real space. The necessary dose for the subcellular level, however, is so high that only postmortem studies are permitted. Although the spatial resolution is high enough to visualize individual biological cells, the contrast is, contrary to hard tissues, too low. Monochromatic X-ray beams, as applied in synchrotron radiation-based μCT (SRμCT), provide much better contrast. Therefore, SRμCT has allowed visualizing individual cells in human tissue after appropriate staining . Grating-based phase-contrast SRμCT has been shown to give rise to even orders of magnitude better contrast for human tissues . Here, non-stained, individual Purkinje cells located in the brain come to light (see Fig. 1). In order to make visible nanostructures between 1 nm and 100 nm in real space, however, X-ray optics have to be integrated into the setup and the accessible volumes become as small as for electron-based techniques.
Diffraction and scattering methods are established techniques to quantitatively characterize the arrangement of atoms or molecules in reciprocal space . Therefore, they give rise to average values within the illuminated volume. The combination of small probing beams and scanning provides spatially resolved data for the nanometer range and below. X-ray-based methods are especially suitable for human tissues. They are termed scanning small-angle X-ray scattering (scanning SAXS) and scanning wide-angle X-ray scattering (scanning WAXS). While SAXS covers the entire nanometer range, WAXS depicts the interatomic distances on the sub-nanometer scale (see Fig. 1).
Key Research Findings
Future Research Directions
The human body is fascinating because of its huge complexity. Clinical CT facilities reach a resolution of a fraction of a millimeter. This limit will not be much shifted toward true micrometer scale, as (i) the amount of data has to be (semi-)automatically analyzed and (ii) the dose becomes dangerous for the patient. Dose reduction has been one of the major research topics in clinical CT. For postmortem visualization, μCT in absorption-contrast mode has been developed to a standard technique. The contrast for soft tissues is so weak that phase-contrast methods are required. Fine-tuning of the most advanced systems is a prerequisite to reveal cellular structures within the organs of the human body. For the visualization of the nanostructures, however, scattering methods seem to be much better suited. Besides the well-established 2D projection data, several approaches for the 3D tomographic reconstruction of tissue anisotropy and orientation were recently presented [13, 14, 15, 16]. These techniques require sophisticated reconstruction algorithms and extended data acquisition times in the order of tens of hours. The wealth of information obtained from such data will however warrant increased interest in these techniques, leading to the development of optimized, faster, and more powerful acquisition protocols.
The structural information of the human body down to the nanometer level will provide a sound basis for developing nature analogue biomaterials and biomimetic implants  to be launched for the benefit of patients. These biomimetic products will exhibit micro- and nanostructures including their preferential orientation (anisotropy) as found in nature and revealed by highly advanced imaging techniques applying sophisticated software tools for data treatment and medical image analysis. Learning from nature will lead to solutions of health problems in our aging society.
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