Soft-Tissue Imaging in a Human Mummy: Propagation-based Phase-Contrast CT.

Purpose To evaluate phase-contrast CT as a noninvasive alternative to histology in the study of ancient soft tissue. Materials and Methods The imaging was performed between May 8 and June 13, 2017. A mummified human hand from ancient Egypt was imaged in a laboratory phase-contrast CT arrangement with propagation-based imaging. The experimental arrangement for propagation-based imaging included a microfocus x-ray source, a rotation stage for the sample, and an x-ray detector. The mummified hand was imaged in two different modes. First, a CT scan of the whole hand was performed in an overview arrangement. Then, a detailed scan of the tip of the middle finger was performed. With imaging distances tailored for a large magnification and to maximize the phase-contrast signal, the estimated resolution in the final images was 6-9 µm. Results The overview CT allowed identification of the tendons of the hand, as well as identification of arteries and nerves in the dehydrated soft tissue. In the detailed phase-contrast setting, virtual histology of the soft tissues of the fingertip could be performed. Blood vessels in the nail bed and the microanatomy of the bone marrow and hypodermis were imaged, and the layers of the skin could be distinguished. Round structures in the adipose tissue were identified as the remains of adipocytes. Conclusion Laboratory phase-contrast CT enables imaging of the anatomy and microanatomy of mummified soft tissue with sub-10-µm resolution and may serve as a complement or alternative to the classic invasive histologic methods used in soft-tissue paleopathology. © RSNA, 2018 Online supplemental material is available for this article.

Cellular-resolution 3D virtual histology of human coronary arteries using x-ray phase tomography.

High-spatial-resolution histology of coronary artery autopsy samples play an important role for understanding heart disease such as myocardial infarction. Unfortunately, classical histology is often destructive, has thick slicing, requires extensive sample preparation, and is time-consuming. X-ray micro-CT provides fast nondestructive 3D imaging but absorption contrast is often insufficient, especially for observing soft-tissue features with high resolution. Here we show that propagation-based x-ray phase-contrast tomography has the resolution and contrast to image clinically relevant soft-tissue features in intact coronary artery autopsy samples with cellular resolution. We observe microscopic lipid-rich plaques, individual adipose cells, ensembles of few foam cells, and the thin fibrous cap. The method relies on a small-spot laboratory x-ray microfocus source, and provides high-spatial resolution in all three dimensions, fast data acquisition, minimum sample distortion and requires no sample preparation.

High-spatial-resolution x-ray fluorescence tomography with spectrally matched nanoparticles.

Present macroscopic biomedical imaging methods provide either morphology with high spatial resolution (e.g. CT) or functional/molecular information with lower resolution (e.g. PET). X-ray fluorescence (XRF) from targeted nanoparticles allows molecular or functional imaging but sensitivity has so far been insufficient resulting in low spatial resolution, despite long exposure times and high dose. In the present paper, we show that laboratory XRF tomography with metal-core nanoparticles (NPs) provides a path to functional/molecular biomedical imaging with ~100 µm resolution in living rodents. The high sensitivity and resolution rely on the combination of a high-brightness liquid-metal-jet x-ray source, pencil-beam optics, photon-counting energy-dispersive detection, and spectrally matched NPs. The method is demonstrated on mice for 3D tumor imaging via passive targeting of in-house-fabricated molybdenum NPs. Exposure times, nanoparticle dose, and radiation dose agree well with in vivo imaging.

Removal of ring artifacts in microtomography by characterization of scintillator variations.

Ring artifacts reduce image quality in tomography, and arise from faulty detector calibration. In microtomography, we have identified that ring artifacts can arise due to high-spatial frequency variations in the scintillator thickness. Such variations are normally removed by a flat-field correction. However, as the spectrum changes, e.g. due to beam hardening, the detector response varies non-uniformly introducing ring artifacts that persist after flat-field correction. In this paper, we present a method to correct for ring artifacts from variations in scintillator thickness by using a simple method to characterize the local scintillator response. The method addresses the actual physical cause of the ring artifacts, in contrary to many other ring artifact removal methods which rely only on image post-processing. By applying the technique to an experimental phantom tomography, we show that ring artifacts are strongly reduced compared to only making a flat-field correction.

High-resolution short-exposure small-animal laboratory x-ray phase-contrast tomography.

X-ray computed tomography of small animals and their organs is an essential tool in basic and preclinical biomedical research. In both phase-contrast and absorption tomography high spatial resolution and short exposure times are of key importance. However, the observable spatial resolutions and achievable exposure times are presently limited by system parameters rather than more fundamental constraints like, e.g., dose. Here we demonstrate laboratory tomography with few-ten µm spatial resolution and few-minute exposure time at an acceptable dose for small-animal imaging, both with absorption contrast and phase contrast. The method relies on a magnifying imaging scheme in combination with a high-power small-spot liquid-metal-jet electron-impact source. The tomographic imaging is demonstrated on intact mouse, phantoms and excised lungs, both healthy and with pulmonary emphysema.

X-ray phase-contrast tomography for high-spatial-resolution zebrafish muscle imaging.

Imaging of muscular structure with cellular or subcellular detail in whole-body animal models is of key importance for understanding muscular disease and assessing interventions. Classical histological methods for high-resolution imaging methods require excision, fixation and staining. Here we show that the three-dimensional muscular structure of unstained whole zebrafish can be imaged with sub-5 µm detail with X-ray phase-contrast tomography. Our method relies on a laboratory propagation-based phase-contrast system tailored for detection of low-contrast 4-6 µm subcellular myofibrils. The method is demonstrated on 20 days post fertilization zebrafish larvae and comparative histology confirms that we resolve individual myofibrils in the whole-body animal. X-ray imaging of healthy zebrafish show the expected structured muscle pattern while specimen with a dystrophin deficiency (sapje) displays an unstructured pattern, typical of Duchenne muscular dystrophy. The method opens up for whole-body imaging with sub-cellular detail also of other types of soft tissue and in different animal models.