Design and Development of a Bioreactor System for Mechanical Stimulation of Musculoskeletal Tissue

We report on the development of a bioreactor system for mechanical stimulation of musculoskeletal tissues. The ultimate object is to improve the quality of medical treatment following injuries of the enthesis tissue. To this end, the tissue formation process through the effect of mechanical stimulation is investigated. A six-well system was designed, 3D printed and tested. An integrated actuator creates strain by applying a force. A contactless position sensor monitors the travels. An electronic circuit controls the bioreactor using a microcontroller. An IoT platform connects the microcontroller to a smartphone, enabling the user to alter variables, trigger actions and monitor the system. The system was stabilised by implementing two PID controllers and safety measures. The results show that the bioreactor design is suited to execute mechanical stimulation and to investigate the tissue formation and regeneration process. The bioreactor reported here can now be implemented in tissue engineering applications including tissue specimen.</p

Extension of the Stoichiometric Calibration of CT Hounsfield values to Metallic Materials

Nowadays, patients with metallic implants undergoing radiotherapy may suffer from inaccuracy in the treatment plan caused by the implant. To ensure a precise plan an accurate relation between Hounsfield values of the computer tomographic (CT) images and the electron density of the elements and material mixtures is indispensable. In order to extend the stoichiometric calibration approach known for tissues to the regime of metallic materials, the basic physical equations as well as approximations in the parametrization and fitting are carefully reviewed. CT images of a standard calibration phantom and pure metallic samples up to the atomic number Z = 29 were acquired for various energies. Hounsfield values were determined on an extended Hounsfield scale which allows the mapping of material having high atomic number Z. It is found that from basic physics an empirical factorization of the cross-sections into a function of Z and a function of photon energy E is not allowed over a wide range of Z. Specifically, the parameterization for tissue like materials cannot be prolonged to materials with high-Z. Thus, the calibration is subdivided into regions of materials and its accuracy is quantified in each region. It depends, among others, on the knowledge of the X-ray photon spectra, the segmentation of the material samples and the empirical parameterization of the linear-attenuation coefficient

Investigation of avascular tumor–immune system interactions using a CA–PDE model

We report on investigations that illustrate the interaction between the specific immune system and a young avascular tumor growing due to a diffusive nutrient supply. We formulate a hybrid cellular automata-partial differential equation (CA-PDE) model which includes cell cycle dynamics and allows for tracking the spatial and temporal evolution of this elaborate biological system. We present results of two dimensional numerical simulations that, specifically in this work, include special cases of the spherical and papillary tumor growth, the infiltration of immune system cells into the tumor and the escape of tumor cells from the regime of the immune cells

Accuracy of CT numbers and electron density calibration for mixtures of materials with low and high-atomic number

In computed tomography (CT) materials with high-atomic number Z cause image artefacts, thus, errors in CT numbers given in Hounsfield Units (HU). Also, the conventional HU scale (CHU) implemented in CT scanners is truncated, i.e., it does not cover high-Z materials. These restrictions lead to incorrect mapping of CT numbers to electron density, which are used in radiotherapy (RT) treatment planning systems (TPS). Even analytical conversion methods are only permissible for tissue-equivalent materials. In terms of HU-to-density conversion in RT TPS, we investigated the CT numbers of material mixtures up to Z<29 at the CHU and an extended-HU (EHU) scale, respectively, and quantify the systematic errors of image artefacts. In [1] the feasibility of a stoichiometric analytical calibration method were analyzed for metals and adapted for higher accurcy, for energies of 80 kV and 120 kV. In this work, we add results for 100 kV and 140 kV to cover the wide diagnostic range. The CT numbers are effected by physical and machine-based properties and depend strongly on the energy, e.g., for Cu a HU difference of 6 171HU at 80 kV and 140 kV occured. The analytical calibration parameters change with energy by a factor between 2 and 10 depending on the physical process. Although for high- Z materials our calibration procedure remains in conflict with rigorous physics [2], it offers an improved and a practical way to predict electron densities from CT numbers

Numerical examinations of simplified spondylodesis models concerning energy absorption in magnetic resonance imaging

Metallic implants in magnetic resonance imaging (MRI) are a potential safety risk since the energy absorption may increase temperature of the surrounding tissue. The temperature rise is highly dependent on implant size. Numerical examinations can be used to calculate the energy absorption in terms of the specific absorption rate (SAR) induced by MRI on orthopaedic implants. This research presents the impact of titanium osteosynthesis spine implants, called spondylodesis, deduced by numerical examinations of energy absorption in simplified spondylodesis models placed in 1.5 T and 3.0 T MRI body coils. The implants are modelled along with a spine model consisting of vertebrae and disci intervertebrales thus extending previous investigations [1], [2]. Increased SAR values are observed at the ends of long implants, while at the center SAR is significantly lower. Sufficiently short implants show increased SAR along the complete length of the implant. A careful data analysis reveals that the particular anatomy, i.e. vertebrae and disci intervertebrales, has a significant effect on SAR. On top of SAR profile due to the implant length, considerable SAR variations at small scale are observed, e.g. SAR values at vertebra are higher than at disc positions

Design and first results of a phantom study on the suitability of iterative reconstruction for lung-cancer screening with low-dose computer tomography

In this research computer tomography (CT) iterative reconstruction (IR) algorithms are investigated, specifically the impact of their statistical and model-based strength on image quality in low-dose lung screening CT protocols in comparison to filtered back projection (FBP). It has been probed whether statistical, model-based IR in conjunction with low-dose, and ultra-low-dose protocols are suitable for lungcancer screening. To this end, artificial lung nodules shaped as spheres and spicules made from material with calibrated Hounsfield units (HU) were attached on marked positions in the lung structure of an anthropomorphic phantom. Nodule positions were selected by distinguished radiologists. The phantom with nodules was scanned on a CT Scanner using standard high contrast (SHC), low-dose (LD) and ultra low-dose (ULD) protocol. For reconstruction FBP and the IR algorithm ADMIRE at three different strength levels were used. Volume CT dose index (CTDIvol) and dose-length product were recorded. Radiologists assessed subjective image quality using a six-point Likert scale by reading all image series in terms detectability of lung nodules. As a measurable objective image quality parameter signal-to-noise ratios (SNR) were investigated. The CTDIvol decreases by more than 70% for all protocols and nodules compared to diagnostic reference value for chest CT (p<0.00001). The evaluation of image quality parameters, i.e. SNR, indicates that LD and ULD protocols in conjunction with IR assert high quality lung-nodule detection. The results reveal that IR algorithm with moderate to high strength is an indispensable alternative to FBP in low-dose scanning, thus, potentially suitable for lung-tumour screening

Validation of iterative CT reconstruction by inter and intra observer performance assessment of artificial lung foci

We investigate the suitability of statistical and model-based iterative reconstruction (IR) algorithm strengths and their influence on image quality and diagnostic performance in low-dose computer tomography (CT) protocols for lung-cancer screening procedures. We evaluate the inter- and intra-observer performance for the assessment of iterative CT reconstruction. Artificial lung foci shaped as spheres and spicules made from material with calibrated Hounsfield units were pressed within layered granules in lung lobes of an anthropomorphic phantom. Adaptively, a soft-tissue- and fat- extension ring were attached. The phantom with foci was scanned using standard high contrast, low-dose and ultra lowdose protocols. For reconstruction the IR algorithm ADMIRE at four different strength levels were used. Two ranking tests and Friedman statistics were performed. Fleiss k and modified Cohen’s kneywere used to quantify inter- and intra-observer performance. In conjunction with the standard lung kernel BL75 radiologists evaluated medium to high IR strength, with preference to S4, as suitable for lung foci detection. When varying reconstruction kernels the ranking became more random than with varying phantom diameter. The inter-observer reliability shows poor to slight agreement expressed by k0.90 for the second ranking test was observed. In conclusion, our validation suggests radiological preference of medium to high iteration strengths, especially S4, for lung foci detection. An investigation of the correlation between diagnostic experience and the subjective perception of IR reconstructed CT images still needs to be investigated

Comparison of treatment plans calculated by Ray Tracing and Monte Carlo algorithms for head and thorax radiotherapy with Cyberknife

This study investigates differences between treatment plans generated by Ray Tracing (RT) and Monte Carlo (MC) calculation algorithms in homogeneous and heterogeneous body regions. Particularly, we focus on the head and on the thorax, respectively, for robotic stereotactic radiotherapy and radiosurgery with Cyberknife. Radiation plans for tumors located in the head and in the thorax region have been calculated and compared to each other in 47 cases and several tumor types

Design and Development of a Bioreactor System for Mechanical Stimulation of Musculoskeletal Tissue

We report on the development of a bioreactor system for mechanical stimulation of musculoskeletal tissues. The ultimate object is to improve the quality of medical treatment following injuries of the enthesis tissue. To this end, the tissue formation process through the effect of mechanical stimulation is investigated. A six-well system was designed, 3D printed and tested. An integrated actuator creates strain by applying a force. A contactless position sensor monitors the travels. An electronic circuit controls the bioreactor using a microcontroller. An IoT platform connects the microcontroller to a smartphone, enabling the user to alter variables, trigger actions and monitor the system. The system was stabilised by implementing two PID controllers and safety measures. The results show that the bioreactor design is suited to execute mechanical stimulation and to investigate the tissue formation and regeneration process. The bioreactor reported here can now be implemented in tissue engineering applications including tissue specimen