Multimodal imaging of the human knee down to the cellular level

Abstract

Abstract. Computed tomography reaches the best spatial resolution for the three-dimensional visualization of human tissues among the available nondestructive clinical imaging techniques. Nowadays, sub-millimeter voxel sizes are regularly obtained. Regarding investigations on true micrometer level, lab-based micro-CT (µCT) has become gold standard. The aim of the present study is firstly the hierarchical investigation of a human knee post mortem using hard X-ray µCT and secondly a multimodal imaging using absorption and phase contrast modes in order to investigate hard (bone) and soft (cartilage) tissues on the cellular level. After the visualization of the entire knee using a clinical CT, a hierarchical imaging study was performed using the labsystem nanotom® m. First, the entire knee was measured with a pixel length of 65 µm. The highest resolution with a pixel length of 3 µm could be achieved after extracting cylindrically shaped plugs from the femoral bones. For the visualization of the cartilage, grating-based phase contrast µCT (I13-2, Diamond Light Source) was performed. With an effective voxel size of 2.3 µm it was possible to visualize individual chondrocytes within the cartilage.

X-ray computed tomography in life sciences

“…For the most part, synchrotron Xray beamlines are highly coherent, giving high contrast interference fringes, which makes PCT relatively straightforward, whereas few laboratory systems currently exhibit sufficient coherence to undertake phase contrast imaging without the use of gratings or masks [31]. PCT is being increasingly applied to the 3D imaging of soft tissues across a wide variety of applications including non-calcified musculoskeletal tissues (such as cartilage and tendon) [32,33], the circulatory system [34] and plants [35]. PCT has proven particularly useful for fossilised specimens, where alternative means of contrast enhancement (such as staining) are not suitable [36].…”

Implementation of a double-grating interferometer for phase-contrast computed tomography in a conventional system nanotom® m

“…As it was previously shown, synchrotron radiation-based grating interferometry enables label-free imaging of a human knee down to the cellular level. 6 It is expected that further sensitivity increase of the laboratory set-up can enable visualizing individual chondrocytes and potentially their automatic counting, which in turn will lead to clear detection of individual cartilage layers.…”

“…38 The system has a temperature stabilized digital GE DXR 500L detector with a pixel size of 100 lm (3072 Â 2400 pixels) based on endurance TM scintillator technology. 39 Experimental parameters 016106- 6 Khimchenko et al APL Bioeng. 2, 016106 (2018) are listed in Table I.…”

“…The synchrotron radiation based XDGI measurements were carried out at the DiamondManchester Imaging Branchline I13-2 (Diamond Light Source, UK) 6 …”

“…In the hard X-ray regime, phase contrast is often preferred over conventional absorption contrast for soft tissue imaging 3,4 and visualizing weak X-ray absorbing species in the direct neighborhood of stronger absorbing components, 5 in particular, for three-dimensional imaging of a cartilage which is involved in the degenerative changes of a joint, [6][7][8][9][10] providing imaging data of morphological features with unprecedented contrast. Disorders associated with cartilage degeneration, such as debilitating joint diseases, are one of the leading causes of disability worldwide.…”