Automated 3D trabecular bone structure analysis of the proximal femur—prediction of biomechanical strength by CT and DXA

The standard diagnostic technique for assessing osteoporosis is dual X-ray absorptiometry (DXA) measuring bone mass parameters. In this study, a combination of DXA and trabecular structure parameters (acquired by computed tomography [CT]) most accurately predicted the biomechanical strength of the proximal femur and allowed for a better prediction than DXA alone. An automated 3D segmentation algorithm was applied to determine specific structure parameters of the trabecular bone in CT images of the proximal femur. This was done to evaluate the ability of these parameters for predicting biomechanical femoral bone strength in comparison with bone mineral content (BMC) and bone mineral density (BMD) acquired by DXA as standard diagnostic technique. One hundred eighty-seven proximal femur specimens were harvested from formalin-fixed human cadavers. BMC and BMD were determined by DXA. Structure parameters of the trabecular bone (i.e., morphometry, fuzzy logic, Minkowski functionals, and the scaling index method [SIM]) were computed from CT images. Absolute femoral bone strength was assessed with a biomechanical side-impact test measuring failure load (FL). Adjusted FL parameters for appraisal of relative bone strength were calculated by dividing FL by influencing variables such as body height, weight, or femoral head diameter. The best single parameter predicting FL and adjusted FL parameters was apparent trabecular separation (morphometry) or DXA-derived BMC or BMD with correlations up to r = 0.802. In combination with DXA, structure parameters (most notably the SIM and morphometry) added in linear regression models significant information in predicting FL and all adjusted FL parameters (up to R adj = 0.872) and allowed for a significant better prediction than DXA alone. A combination of bone mass (DXA) and structure parameters of the trabecular bone (linear and nonlinear, global and local) most accurately predicted absolute and relative femoral bone strength

Accelerated stem cell labeling with ferucarbotran and protamine

To develop and characterize a clinically applicable, fast and efficient method for stem cell labeling with ferucarbotran and protamine for depiction with clinical MRI. The hydrodynamic diameter, zeta potential and relaxivities of ferucarbotran and varying concentrations of protamine were measured. Once the optimized ratio was found, human mesenchymal stem cells (MSCs) were labeled at varying incubation times (1–24 h). Viability was assessed via Trypan blue exclusion testing. 150,000 labeled cells in Ficoll solution were imaged with T1-, T2- and T2*-weighted sequences at 3 T, and relaxation rates were calculated. Varying the concentrations of protamine allows for easy modification of the physicochemical properties. Simple incubation with ferucarbotran alone resulted in efficient labeling after 24 h of incubation while assisted labeling with protamine resulted in similar results after only 1 h. Cell viability remained unaffected. R2 and R2* relaxation rates were drastically increased. Electron microscopy confirmed intracellular iron oxide uptake in lysosomes. Relaxation times correlated with results from ICP-AES. Our results show internalization of ferucarbotran can be accelerated in MSCs with protamine, an approved heparin antagonist and potentially clinically applicable uptake-enhancing agent

In-vivo X-ray Dark-Field Chest Radiography of a Pig

X-ray chest radiography is an inexpensive and broadly available tool for initial assessment of the lung in clinical routine, but typically lacks diagnostic sensitivity for detection of pulmonary diseases in their early stages. Recent X-ray dark-field (XDF) imaging studies on mice have shown significant improvements in imaging-based lung diagnostics. Especially in the case of early diagnosis of chronic obstructive pulmonary disease (COPD), XDF imaging clearly outperforms conventional radiography. However, a translation of this technique towards the investigation of larger mammals and finally humans has not yet been achieved. In this letter, we present the first in-vivo XDF full-field chest radiographs (32 × 35 cm²) of a living pig, acquired with clinically compatible parameters (40s scan time, approx. 80 μSv dose). For imaging, we developed a novel high-energy XDF system that overcomes the limitations of currently established setups. Our XDF radiographs yield sufficiently high image quality to enable radiographic evaluation of the lungs. We consider this a milestone in the bench-to-bedside translation of XDF imaging and expect XDF imaging to become an invaluable tool in clinical practice, both as a general chest X-ray modality and as a dedicated tool for high-risk patients affected by smoking, industrial work and indoor cooking

Diagnosis, staging and treatment of hepatocellular carcinoma

Hepatocellular carcinomas are aggressive tumors with a high dissemination power. An early diagnosis of these tumors is of great importance in order to offer the possibility of curative treatment. For an early diagnosis, abdominal ultrasound and serum alpha-fetoprotein determinations at 6-month intervals are suggested for all patients with cirrhosis of the liver, since this disease is considered to be the main risk factor for the development of the neoplasia. Helicoidal computed tomography, magnetic resonance and/or hepatic arteriography are suggested for diagnostic confirmation and tumor staging. The need to obtain a fragment of the focal lesion for cytology and/or histology for a diagnosis of hepatocellular carcinoma depends on the inability of imaging methods to diagnose the lesion. Several classifications are currently available for tumor staging in order to determine patient prognosis. All take into consideration not only the stage of the tumor but also the degree of hepatocellular dysfunction, which is known to be the main factor related to patient survival. Classifications, however, fail to correlate treatment with prognosis and cannot suggest the ideal treatment for each tumor stage. The Barcelona Classification (BCLC) attempts to correlate tumor stage with treatment but requires prospective studies for validation. For single tumors smaller than 5 cm or up to three nodules smaller than 3 cm, surgical resection, liver transplantation and percutaneous treatment may offer good anti-tumoral results, as well as improved patient survival. Embolization or chemoembolization are therapeutic alternatives for patients who do not benefit from curative therapies