Images from MARS spectral CT scanners show that there is much diagnostic value from using small pixels and good energy data. MARS scanners use energy-resolving photon-counting CZT Medipix3RX detectors that measure the energy of photons on a five-point scale and with a spatial resolution of 110 microns. The energy information gives good material discrimination and quantification. The 3D reconstruction gives a voxel size of 70 microns. We present images of pre-clinical specimens, including excised atheroma, bone and joint samples, and nanoparticle contrast agents along with images from living humans. Images of excised human plaque tissue show the location and extent of lipid and calcium deposition within the artery wall. The presence of intraplaque haemorrhage, where the blood leaks into the artery wall following a rupture, has also been visualised through the detection of iron. Several clinically important bone and joint problems have been investigated including: site-specific bone mineral density, bone-metal interfaces (spectral CT reduces metal artefacts), cartilage health using ionic contrast media, gout and pseudogout crystals, and microfracture assessment using nanoparticles. Metallic nanoparticles have been investigated as a cellular marker visible in MARS images. Cell lines of different cancer types (Raji and SK-BR3) were incubated with monoclonal antibody-functionalised AuNPs (Herceptin and Rituximab). We identified and quantified the labelled AuNPs demonstrating that Herceptin-functionalised AuNPs bound to SK-BR3 breast cancer cells but not to the Raji lymphoma cells. In vivo human images show the bone microstructure. Fat, water, and calcium concentrations are quantifiable.
The aim is to perform qualitative and quantitative assessment of metal induced artefacts of small titanium biomaterials using photon counting spectral CT. The energy binning feature of some photon counting detectors enables the measured spectrum to be segmented into low, mid and high energy bins in a single exposure. In this study, solid and porous titanium implants submerged in different concentrations of calcium solution were scanned using the small animal MARS photon counting spectral scanner equipped with a polyenergetic X-ray source operated at 118 kVp. Five narrow energy bins (7-45 keV, 45-55 keV, 55-65 keV, 65-75 keV and 75-118 keV) in charge summing mode were utilised. Images were evaluated in the energy domain (spectroscopic images) as well as material domain (material segmentation and quantification). Results show that calcium solution outside titanium implants can be accurately quantified. However, there was an overestimation of calcium within the pores of the scaffold. This information is critical as it can severely limit the assessment of bone ingrowth within metal structures. The energy binning feature of the spectral scanner was exploited and a correction factor, based on calcium concentrations adjacent to and within metal structures, was used to minimise the variation. Qualitative and quantitative evaluation of bone density and morphology with and without titanium screw shows that photon counting spectral CT can assess bone-metal interface with less pronounced artefacts. Quantification of bone growth in and around the implants would help in orthopaedic applications to determine the effectiveness of implant treatment and assessment of fracture healing.
Purpose: We aimed to determine the in-vitro diagnostic performance of multi-energy spectral photon-counting CT (SPCCT) in crystal-related arthropathies. Methods: Four crystal types (monosodium urate, MSU; calcium pyrophosphate, CPP; octacalcium phosphate, OCP; and calcium hydroxyapatite, CHA) were synthesized and blended with agar at the following concentrations: 240, 88, 46, and 72 mg/mL, respectively. Crystal suspensions were scanned on a pre-clinical SPCCT system at 80 kVp using the following four energy thresholds: 20, 30, 40, and 50 keV. Differences in linear attenuation coefficients between the various crystal suspensions were compared using the receiver operating characteristic (ROC) paradigm. Areas under the ROC curves (AUC), sensitivities, specificities, and diagnostic accuracies were calculated. Crystal differentiation was considered successful if AUC>0.95. Results: For each paired comparison of crystal suspensions, AUCs were significantly higher in the first energy range (20-30 keV). In the first energy range, MSU was confidently differentiated from CPP (sensitivity, 0.978; specificity, 0.990; accuracy, 0.984) and CHA (sensitivity, 0.957; specificity, 0.970; accuracy, 0.964), while only moderately distinguished from OCP (sensitivity, 0.663; specificity, 0.714; accuracy, 0.688). CPP was confidently differentiated from OCP (sensitivity, 0.950; specificity, 0.954; accuracy, 0.952), while only moderately from CHA (sensitivity, 0.564; specificity, 0.885; accuracy, 0.727). OCP was accurately differentiated from CHA (sensitivity, 0.898; specificity, 0.917; accuracy, 0.907). Conclusions: Multi-energy SPCCT can accurately differentiate MSU from CPP and CHA, CPP from OCP, and OCP from CHA in vitro. The distinction between MSU and OCP, and CPP and CHA is more challenging.
Calcium compounds within tissues are usually a sign of pathology, and calcium crystal type is often a pointer to the diagnosis. There are clinical advantages in being able to determine the quantity and type of calcifications non-invasively in cardiovascular, genitourinary and musculoskeletal disorders, and treatment differs depending on the crystal type and quantity. The problem arises when trying to distinguish between different calcium compounds within the same image due to their similar attenuation properties. There are spectroscopic differences between calcium salts at very low energies. As calcium oxalate and calcium hydroxyapatite can co-exist in breast and musculoskeletal pathologies of the breast, we wished to determine whether Spectral CT could distinguish between them in the same image at clinical X-ray energy ranges. Energy thresholds of 15, 22, 29 and 36keV and tube voltages of 50, 80 and 110kVp were chosen, and images were analysed to determine the percentage difference in the attenuation coefficients of calcium hydroxyapatite samples at concentrations of 54.3, 211.7, 808.5 and 1169.3mg/ml, and calcium oxalate at a concentration of 2000 mg/ml. The two lower concentrations of calcium hydroxyapatite were distinguishable from calcium oxalate at all energies and all tube voltages, whereas the ability to discriminate oxalate from hydroxyapatite at higher concentrations was dependent on the threshold energy but only mildly dependent on the tube voltage used. Spectral CT shows promise for distinguishing clinically important calcium salts.
Combining bone structure and density measurement in 3D is required to assess site-specific fracture risk. Spectral
molecular imaging can measure bone structure in relation to bone density by measuring macro and microstructure of bone
in 3D. This study aimed to optimize spectral CT methodology to measure bone structure in excised bone samples. MARS
CT with CdTe Medipix3RX detector was used in multiple energy bins to calibrate bone structure measurements. To
calibrate thickness measurement, eight different thicknesses of Aluminium (Al) sheets were scanned one in air and the
other around a falcon tube and then analysed. To test if trabecular thickness measurements differed depending on scan
plane, a bone sample from sheep proximal tibia was scanned in two orthogonal directions. To assess the effect of air on
thickness measurement, two parts of the same human femoral head were scanned in two conditions (in the air and in PBS).
The results showed that the MARS scanner (with 90μm voxel size) is able to accurately measure the Al (in air) thicknesses
over 200μm but it underestimates the thicknesses below 200μm because of partial volume effect in Al-air interface. The
Al thickness measured in the highest energy bin is overestimated at Al-falcon tube interface. Bone scanning in two
orthogonal directions gives the same trabecular thickness and air in the bone structure reduced measurement accuracy. We
have established a bone structure assessment protocol on MARS scanner. The next step is to combine this with bone
densitometry to assess bone strength.