Commissioning of a Versa HDTM linear accelerator for three commercial treatment planning systems.

In a mixed-vendor radiation oncology environment, it is advantageous if the department's treatment planning system (TPS) supports the linear accelerators of different vendors. In this publication beam data collection and modeling for the Versa HD linear accelerator in Monaco, Pinnacle, and Eclipse are discussed. In each TPS static field, Intensity-Modulated Radiation Therapy (IMRT) step and shoot, and Volumetric-Modulated Arc Therapy (VMAT) plans for flattened and flattening-filter free photon beams of all available energies were evaluated for field sizes >3 × 3. To compare passing rates, identical beam model validation plans were calculated in each TPS. Eclipse, Monaco, and Pinnacle beam models passed validation measurements in homogeneous materials for a variety of treatment fields, including static, IMRT, and VMAT. In the case of Eclipse, the "dosimetric leaf gap" parameter was found to be critical for passing rates of VMAT plans. The source size parameter plays an important role as well for small fields. In the case of Pinnacle the multileaf collimator offset table needed to be optimized for better VMAT QA results. Each of the investigated treatment planning systems met the criteria to be used clinically in conjunction with Elekta Versa HD linear accelerators. It can be of great advantage to have the option to operate a TPS and linear accelerator from different vendors, as decisions surrounding linear accelerator or TPS purchases are very complicated and not just limited to technical considerations.

Registration of phase-contrast images in propagation-based X-ray phase tomography.

X-ray phase tomography aims at reconstructing the 3D electron density distribution of an object. It offers enhanced sensitivity compared to attenuation-based X-ray absorption tomography. In propagation-based methods, phase contrast is achieved by letting the beam propagate after interaction with the object. The phase shift is then retrieved at each projection angle, and subsequently used in tomographic reconstruction to obtain the refractive index decrement distribution, which is proportional to the electron density. Accurate phase retrieval is achieved by combining images at different propagation distances. For reconstructions of good quality, the phase-contrast images recorded at different distances need to be accurately aligned. In this work, we characterise the artefacts related to misalignment of the phase-contrast images, and investigate the use of different registration algorithms for aligning in-line phase-contrast images. The characterisation of artefacts is done by a simulation study and comparison with experimental data. Loss in resolution due to vibrations is found to be comparable to attenuation-based computed tomography. Further, it is shown that registration of phase-contrast images is nontrivial due to the difference in contrast between the different images, and the often periodical artefacts present in the phase-contrast images if multilayer X-ray optics are used. To address this, we compared two registration algorithms for aligning phase-contrast images acquired by magnified X-ray nanotomography: one based on cross-correlation and one based on mutual information. We found that the mutual information-based registration algorithm was more robust than a correlation-based method.

Characterizing microcrack orientation distribution functions in osteonal bone samples.

Prefailure microdamage in bone tissue is considered to be the most detrimental factor in defining its strength and toughness with respect to age and disease. To understand the influence of microcracks on bone mechanics it is necessary to assess their morphology and three-dimensional distribution. This requirement reaches beyond classic histology and stereology, and methods to obtain such information are currently missing. Therefore, the aim of the study was to develop a methodology that allows to characterize three-dimensional microcrack distributions in bulk bone samples. Four dumbbell-shaped specimens of human cortical bone of a 77-year-old female donor were loaded beyond yield in either tension, compression or torsion (one control). Subsequently, synchrotron radiation micro-computed tomography (SRµCT) was used to obtain phase-contrast images of the damaged samples. A microcrack segmentation algorithm was developed and used to segment microcrack families for which microcrack orientation distribution functions were determined. Distinct microcrack families were observed for each load case that resulted in distinct orientation distribution functions. Microcracks had median areas of approximately 4.7 µm2 , 33.3 µm2 and 64.0 µm2 for tension, compression and torsion. Verifying the segmentation algorithm against a manually segmented ground truth showed good results when comparing the microcrack orientation distribution functions. A size dependence was noted when investigating the orientation distribution functions with respect to the size of the volume of interest used for their determination. Furthermore, a scale separation between tensile, compressive and torsional microcracks was noticeable. Visual comparison to classic histology indicated that microcrack families were successfully distinguished. We propose a methodology to analyse three-dimensional microcrack distributions in overloaded cortical bone. Such information could improve our understanding of bone microdamage and its impact on bone failure in relation to tissue age and disease.

Clinical radiation therapy measurements with a new commercial synthetic single crystal diamond detector.

A commercial version of a synthetic single crystal diamond detector (SCDD) in a Schottky diode configuration was recently released as the new type 60019 microDiamond detector (PTW-Freiburg, Germany). In this study we investigate the dosimetric properties of this detector to independently confirm that findings from the developing group of the SCDDs still hold true for the commercial version of the SCDDs. We further explore if the use of the microDiamond detector can be expanded to high-energy photon beams of up to 15 MV and to large field measure- ments. Measurements were performed with an Elekta Synergy linear accelerator delivering 6, 10, and 15 MV X-rays, as well as 6, 9, 12, 15, and 20 MeV electron beams. The dependence of the microdiamond detector response on absorbed dose after connecting the detector was investigated. Furthermore, the dark current of the diamond detector was observed after irradiation. Results are compared to similar results from measurements with a diamond detector type 60003. Energy dependency was investigated, as well. Photon depth-dose curves were measured for field sizes 3 × 3, 10 × 10, and 30 × 30 cm2. PDDs were measured with the Semiflex type 31010 detector, microLion type 31018 detector, P Diode type 60016, SRS Diode type 60018, and the microDiamond type 60019 detector (all PTW-Freiburg). Photon profiles were measured at a depth of 10 cm. Electron depth-dose curves normalized to the dose maximum were measured with the 14 × 14 cm2 electron cone. PDDs were measured with a Markus chamber type 23343, an E Diode type 60017 and the microDiamond type 60019 detector (all PTW-Freiburg). Profiles were measured with the E Diode and microDiamond at half of D90, D90, D70, and D50 depths and for electron cone sizes of 6 × 6 cm2, 14 × 14 cm2, and 20 × 20 cm2. Within a tol- erance of 0.5% detector response of the investigated detector was stable without any preirradiation. After preirradition with approximately 250 cGy the detector response was stable within 0.1%. A dark current after irradiation was not observed. The microDiamond detector shows no energy dependence in high energy photon or electron dosimetry. Electron PDD measurements with the E Diode and micro- Diamond are in good agreement. However, compared to E Diode measurements, dose values in the bremsstrahlungs region are about 0.5% lower when measured with the microDiamond detector. Markus detector measurements agree with E Diode measurements in the bremsstrahlungs region. For depths larger than dmax, depth-dose curves of photon beams measured with the microDiamond detector are in close agreement to those measured with the microLion detector for small fields and with those measured with a Semiflex 0.125 cc ionization chamber for large fields. Differences are in the range of 0.25% and less. For profile measurements, microDiamond detector measurements agree well with microLion and P Diode measurements in the high-dose region of the profile and the penumbra region. For areas outside the open field, P Diode measurements are about 0.5%-1.0% higher than microDiamond and microLion measurements. Thus it becomes evident that the investigated diamond detector (type 60019) is suitable for a wide range of applications in high-energy photon and electron dosimetry and is interesting for relative, as well as absolute, dosimetry. 

Circumferential or sectored beam arrangements for stereotactic body radiation therapy (SBRT) of primary lung tumors: effect on target and normal-structure dose-volume metrics.

To compare 2 beam arrangements, sectored (beam entry over ipsilateral hemithorax) vs circumferential (beam entry over both ipsilateral and contralateral lungs), for static-gantry intensity-modulated radiation therapy (IMRT) and volumetric-modulated arc therapy (VMAT) delivery techniques with respect to target and organs-at-risk (OAR) dose-volume metrics, as well as treatment delivery efficiency. Data from 60 consecutive patients treated using stereotactic body radiation therapy (SBRT) for primary non-small-cell lung cancer (NSCLC) formed the basis of this study. Four treatment plans were generated per data set: IMRT/VMAT plans using sectored (-s) and circumferential (-c) configurations. The prescribed dose (PD) was 60Gy in 5 fractions to 95% of the planning target volume (PTV) (maximum PTV dose ~ 150% PD) for a 6-MV photon beam. Plan conformality, R50 (ratio of volume circumscribed by the 50% isodose line and the PTV), and D2cm (Dmax at a distance ≥2cm beyond the PTV) were evaluated. For lungs, mean doses (mean lung dose [MLD]) and percent V30/V20/V10/V5Gy were assessed. Spinal cord and esophagus Dmax and D5/D50 were computed. Chest wall (CW) Dmax and absolute V30/V20/V10/V5Gy were reported. Sectored SBRT planning resulted in significant decrease in contralateral MLD and V10/V5Gy, as well as contralateral CW Dmax and V10/V5Gy (all p < 0.001). Nominal reductions of Dmax and D5/D50 for the spinal cord with sectored planning did not reach statistical significance for static-gantry IMRT, although VMAT metrics did show a statistically significant decrease (all p < 0.001). The respective measures for esophageal doses were significantly lower with sectored planning (p < 0.001). Despite comparable dose conformality, irrespective of planning configuration, R50 significantly improved with IMRT-s/VMAT-c (p < 0.001/p = 0.008), whereas D2cm significantly improved with VMAT-c (p < 0.001). Plan delivery efficiency improved with sectored technique (p < 0.001); mean monitor unit (MU)/cGy of PD decreased from 5.8 ± 1.9 vs 5.3 ± 1.7 (IMRT) and 2.7 ± 0.4 vs 2.4 ± 0.3 (VMAT). The sectored configuration achieves unambiguous dosimetric advantages over circumferential arrangement in terms of esophageal, contralateral CW, and contralateral lung sparing, in addition to being more efficient at delivery.

Identification of a crushable foam material model and application to strength and damage prediction of human femur and vertebral body.

Finite element (FE) models allow quantitative predictions of bone strength and fracture location and, thus, became increasingly popular for assessing fracture risk or effectiveness of osteoporosis therapies. However, predictions crucially depend on the used material models, which are usually complex and rely on a large number of parameters. Therefore, the goal of this study was to propose a simple crushable foam (CF) material model and to perform an extensive comparison with data from the literature. Material parameters of the CF plasticity model were identified based on previously published yield stress data. Voxel-based FE models of thirty-six femora pairs and thirty-eight vertebral bodies were generated from QCT images. The femora models were analyzed with boundary conditions simulating one-legged stance and fall on the greater trochanter. The vertebral body models were subjected to uniaxial compression. Load-displacement curves, ultimate forces and damage distributions computed with the CF material model were compared to a reference material model as well as to in vitro experiments. The result showed that the FE models with CF material provided reasonable quantitative predictions of the ultimate forces measured in the experiments (R(2)>0.80). Comparison of the FE results obtained with CF and reference material model showed very similar outcomes regarding ultimate force, load-displacement behavior and damage patterns for all investigated anatomical sites and loading conditions. In conclusion, the identified CF material model provided good strength and damage predictions, required only few material parameters and is already implemented in many commercial FE solvers. Thus, it can be easily used in other studies.

A generalized anisotropic quadric yield criterion and its application to bone tissue at multiple length scales.

Nonlinear computational analysis of materials showing elasto-plasticity or damage relies on knowledge of their yield behavior and strengths under complex stress states. In this work, a generalized anisotropic quadric yield criterion is proposed that is homogeneous of degree one and takes a convex quadric shape with a smooth transition from ellipsoidal to cylindrical or conical surfaces. If in the case of material identification, the shape of the yield function is not known a priori, a minimization using the quadric criterion will result in the optimal shape among the convex quadrics. The convexity limits of the criterion and the transition points between the different shapes are identified. Several special cases of the criterion for distinct material symmetries such as isotropy, cubic symmetry, fabric-based orthotropy and general orthotropy are presented and discussed. The generality of the formulation is demonstrated by showing its degeneration to several classical yield surfaces like the von Mises, Drucker-Prager, Tsai-Wu, Liu, generalized Hill and classical Hill criteria under appropriate conditions. Applicability of the formulation for micromechanical analyses was shown by transformation of a criterion for porous cohesive-frictional materials by Maghous et al. In order to demonstrate the advantages of the generalized formulation, bone is chosen as an example material, since it features yield envelopes with different shapes depending on the considered length scale. A fabric- and density-based quadric criterion for the description of homogenized material behavior of trabecular bone is identified from uniaxial, multiaxial and torsional experimental data. Also, a fabric- and density-based Tsai-Wu yield criterion for homogenized trabecular bone from in silico data is converted to an equivalent quadric criterion by introduction of a transformation of the interaction parameters. Finally, a quadric yield criterion for lamellar bone at the microscale is identified from a nanoindentation study reported in the literature, thus demonstrating the applicability of the generalized formulation to the description of the yield envelope of bone at multiple length scales.

Depolarization-induced retrograde synaptic inhibition in the mouse cerebellar cortex is mediated by 2-arachidonoylglycerol.

Endocannabinoids acting on CB(1) cannabinoid receptors are involved in short- and long-term depression of synaptic transmission. The aim of the present study was to determine which endocannabinoid, anandamide or 2-arachidonoylglycerol (2-AG), is involved in depolarization-induced suppression of inhibition (DSI) in the cerebellar cortex, which is the most widely studied form of short-term depression. Depolarization of Purkinje cells in the mouse cerebellum led to an increase in intracellular calcium concentration and to suppression of the inhibitory input to these neurons (i.e. DSI occurred). Orlistat and RHC80267, two blockers of sn-1-diacylglycerol lipase, the enzyme catalysing 2-AG formation, abolished DSI by acting downstream of calcium influx. In contrast, DSI occurred also in the presence of a phospholipase C inhibitor. Intact operation of the calcium-dependent messengers calmodulin and Ca(2+)-calmodulin-dependent protein kinase II were necessary for DSI. DSI was potentiated by an inhibitor of the main 2-AG-degrading enzyme, monoacylglycerol lipase. Interference with the anandamide metabolizing enzyme, fatty acid amide hydrolase, did not modify DSI. Thus, three kinds of observations identified 2-AG as the endocannabinoid involved in DSI in the mouse cerebellum: DSI was abolished by diacylglycerol lipase inhibitors; DSI was potentiated by a monoglyceride lipase inhibitor; and DSI was not changed by an inhibitor of fatty acid amide hydrolase. Further experiments indicated that 2-AG is the endocannabinoid mediating short-term retrograde signalling also at other synapses: orlistat abolished DSI in the rat cerebellum, DSI in the mouse substantia nigra pars reticulata and depolarization-induced suppression of excitation in the mouse cerebellum.

Monte Carlo dose calculations in the treatment of a pelvis with implant and comparison with pencil-beam calculations.

In the present paper, dose distribution calculated with the Monte Carlo code EGS4 and with a pencil-beam algorithm are compared for the treatment of a pelvis with an implant. Overestimations of dose values inside the target volume by the pencil-beam algorithm of up to 10% were found, which are attributed to the underestimation of the absorption of photons by the implant. The differences in dose distributions are also expressed by comparing the tumor control probability (TCP) of the Monte Carlo dose calculations with the TCP of the pencil-beam calculations. A TCP reduction of order of 30% was found.

The volume effect of detectors in the dosimetry of small fields used in IMRT.

In this study we investigate the effect of detector size in the dosimetry of small fields and steep dose gradients with a particular emphasis on IMRT measurements. Comparisons of calculated and measured cross-profiles and absolute dose values of IMRT treatment plans are presented. As a consequence of the finite size of the detector that was used for the commissioning of the IMRT tool, local discrepancies of more than 10% are found between calculated cross-profiles of intensity modulated beams and intensity modulated profiles measured with film. Absolute dose measurements of intensity modulated fields with a 0.6 cm3 Farmer chamber show significant differences of more than 6% between calculated and measured dose values at the isocenter of an IMRT treatment plan. Differences of not more than 2% are found in the same experiment for dose values measured with a 0.015 cm3 pinpoint ion chamber. A method to correct for the spatial response of finite-sized detectors and to obtain the "real" penumbra width of cross-profiles from measurements is introduced. Output factor measurements are performed with different detectors and are presented as a function of detector size for a 1 x 1 cm2 field. Because of its high spatial resolution and water equivalence, a diamond detector is found to be suitable as an alternative to other detectors used for small field dosimetry as there are photographic and photochromic film, TLDs, or water-equivalent scintillation detectors.

Comparison of TG-43 dose calculations to pinpoint ion chamber and diamond detector measurements.

Brachytherapy is an area of radiation therapy where the availability of high-resolution detectors with a low energy-dependence is of great importance. The suitability of two detectors is investigated in this study. Measurements in the proximity of an Ir-192 source were performed with a diamond detector type 60003 and a pinpoint chamber type 31006 (both PTW-Freiburg). For comparison, dose values were calculated with the dose calculation formalism recommended by the task group 43 (Nath et al 1995 Med. Phys. 22 209-34).

[Medium-term results using the cement-free link endoprosthesis. Ribbed shaft V socket]. / Mittelfristige Ergebnisse mit der zementfreien "link"-Endoprothese. Rippenschaft-Typ V Schraubring.

Since 3/84 340 primary implantations with the uncemented "Link" hip system (Rib-Type V socket) were done. The results with an average follow up of 3.2 years are published. Only 2.17% revision had to be suffered in the rib stem, while 0.77% socket revision had to be done. According to the score of Merle d'Aubigné the values of pain increased from 2.87% to 5.38%, walking ability from 3.68% to 5.27% and the range of motion from 133 degrees to 199 degrees. A high rate of good and satisfying results proved this anatomical implant system to be a good alternative in total hip replacement in younger patients.

Electroencephalography and evoked potentials: a PC-based analysis program for laboratory courses in physiology.

A computer program (EEG Analysis) was developed for the preclinical laboratory course in physiology held for medical and dental students. It offers an off-line analysis of a set of typical and frequently occurring physiological and pathological electroencephalogram (EEG) and evoked potential (EP) recordings, which are stored in an IBM-compatible personal computer (PC) system. The users are requested to measure and analyze the data sets and to work through a base of questions relevant in the frame of the particular topic. The program is structured in several exercises: calibration, pickup of non-EEG signals (eye movements, chewing), waveforms in EEG recordings from awake subjects (alpha-waves, beta-waves), desynchronization of cerebral activity (visual activation, acoustic activation, mental activation), habituation of cerebral activity upon acoustic stimuli, EEG recordings from asleep subjects (different sleep stages, sleep-specific EEG signals), epileptic seizures, and EPs (principle of averaging, visually evoked potentials in different cortical areas). The program runs under MS-DOS and is network capable. The software structure ensures maximal flexibility for rapid changes and adaptations of the program to specific needs of a particular EEG course. The program has been used for three years, and the response from > 800 students has been consistently positive.

The contractile response of vascular smooth muscle to thrombin and its inhibition by thrombin inhibitors.

Thrombin (0.1-30 NIH-U/ml) caused a contractile response of rabbit aortic rings. The vasocontraction was independent upon intact endothelium, however in deendothelialized vessels the contractile effect was more pronounced. The thrombin-induced vasocontraction was diminished in calcium-free medium; the same effect was attained by the calcium channel blocker verapamil at high concentrations. In human femoral and saphenous vein strips thrombin produced a contractile effect, too, which was very low and inconsistent in femoral arterial strips. To inhibit the contractile response of vascular smooth muscle to thrombin, higher concentrations of both the specific tight-binding inhibitors hirudin and beta Nas-Gly-(pAM)Phe-Pip were required than for the inhibition of fibrinogen clotting.

Dailysate calcium and plasma calcium fractions during and after haemodialysis.

Dialysate calcium and plasma calcium fractions during and after haemodialysis: The effect of differenct dialysate Ca concentrations on the plasma Ca fractions was examined in 28 patients. In 10 patients dialysed with a dialysate Ca concentration of 3.0 mEq/l the Ca fractions were determined at the start and end of dialysis. 8 patients were dialysed with dialysate with dialysate Ca of 3.5 mEq/l. In this group the Ca fractions were also estimated in the dialysis-free interval. The third group was dialysed with a dialysate Ca of 4.5 mEq/l. Total calcium and protein-bound calcium rose significantly in all groups. Ionised calcium in the first group was significantly reduced, in the second group it remained constant and in the third group it was significantly raised. Since parathyroid function depends on the plasma ionised calcium it is concluded that a dialysed concentration of 3.0 mEq/l is partly responsible for the pathogenesis of secondary hyperparathyroidism and of renal osteodystophy. In normocalcaemic patients a dialysate Ca concentration of 3.5 to 4.0 mEq/l is optimal. In patients entering long-term haemodialysis treatment with pronounced calcium deficiency symptoms a dialysate Ca of up to 4.5 mEq/l may be indicated for a short period after having normalized the inorganic phosphate levels in order to prevent extraosseous calcification.