Endorectal digital prostate tomosynthesis (endoDPT): a proof-of-concept study.

In this study we present endorectal digital prostate tomosynthesis (endoDPT), a proposed method of high resolution prostate imaging using an endorectal x-ray sensor and an external x-ray source. endoDPT may be useful for visualizing the fine detail of small structures such as low dose rate brachytherapy (LDRBT) seeds that are difficult to visualize with current methods. The resolution of endoDPT was characterized through measurement of the modulation transfer function (MTF) and artifact spread function (ASF) in computational and physical phantoms. The qualitative resolution of endoDPT was assessed relative to computed tomography (CT) through imaging of LDRBT seeds implanted inex vivocanine prostates. The x-ray sensor MTF reached 10% at 11.50 mm-1, the reconstruction algorithm MTF reached a maximum at 7.08 mm-1, and the ASF was 2.5 mm (full-width at half-maximum). Fine structures in LDRBT seeds like the 0.05 mm thick shell were visible with endoDPT but not CT. All endoDPT images exhibited an overshoot artifact. The measured MTFs were consistent with other studies using similar x-ray sensors and demonstrated improved resolution compared to digital breast tomosynthesis; this result was due to the smaller endoDPT x-ray sensor detection element size and quantitatively demonstrates the high resolution of endoDPT. The ASF demonstrated worse depth resolution compared to in-plane resolution, due to partial angular sampling; partial angular sampling also caused the observed overshoot artifact in the endoDPT images. However, endoDPT still was able to visualize fine structures such as the LDRBT seed shell to a much higher degree than CT. This high-resolution visualization may be useful for improvements in patient specific LDRBT dosimetry. Overall, these results indicate endoDPT is capable of high in-plane spatial resolution and is thus well poised for optimization and studies assessing clinical utility.

IGF1 does not overcome sexual dimorphism of body and muscle size in Mstn-/- mice.

Insulin-like growth factor-1 (IGF1) is crucial for regulating post-natal growth and, along with myostatin (MSTN), regulates muscle size. Here, we sought to clarify the roles of these two genes in regulating sexually dimorphic growth of body and muscle mass. In the first study, we established that Igf1 mRNA was increased to a greater extent and Igf1 receptor mRNA increased earlier in male, than in female, gastrocnemius muscles during the rapid phase of growth (from 2 to 6 weeks) were unchanged, thereafter, to 32 weeks of age in WT mice (P < 0.001). In the second study, we sought to determine if supplemental IGF1 could overcome the sexual dimorphism of muscle and body mass, when myostatin is absent. We crossed myostatin null (Mstn-/-) mice with mice over-expressing Igf1 in skeletal muscle (Igf1+) to generate six genotypes; control (Mstn+/+), Mstn+/-, Mstn-/-, Mstn+/+:Igf1+, Mstn+/-:Igf1+ and Mstn-/-:Igf1+ (n = 8 per genotype and sex). In both sexes, body mass at 12 weeks was increased by at least 1.6-fold and muscle mass by at least 3-fold in Mstn-/-:Igf1+ compared with Mstn+/+ mice (P < 0.001). The abundance of AKT was increased in muscles of mice transgenic for Mstn, while phosphorylation of AKTS473 was increased in both male and female mice transgenic for Igf1+. The ratio of phosphorylated to total AKT was 1.9-fold greater in male mice (P < 0.001). Thus, despite increased growth of skeletal muscle and body size when myostatin was absent and IGF1 was in excess, sexual dimorphism persisted, an effect consistent with greater IGF1-induced activation of AKT in skeletal muscles of males.

Determination of Uranium Series Activity Before Secular Equilibrium Is Established.

Timely achievement of uranium series' secular equilibrium is not always feasible. Our objective is to mathematically justify methods for early uranium series gamma spectroscopy measurements that can accurately predict naturally occurring radioactive material equilibrium activities long before equilibrium is established. It was believed that, regardless of prior Rn escape, after sealing a sample for a few hours the activities of Rn, Ra, and U could theoretically be determined with a single measurement of both Pb and Bi. However, when accounting for error, this theory did not work as expected (CV = 14.0 in Ra simulation). A similar approach published by Li et al. in 2015 proved to be much more reliable with the error considered, using Pb activities measured at two different times gave significantly improved results when tested the same way (CV = 0.29 in Ra simulation). Because both Pb and Bi activities are typically available when using gamma spectrometry, we combine these approaches and further increased the accuracy of the calculated activities (CV = 0.21 in Ra simulation).

Magnetic resonance elastography of the brain: A study of feasibility and reproducibility using an ergonomic pillow-like passive driver.

Magnetic resonance elastography (MRE) can be used to noninvasively resolve the displacement pattern of induced mechanical waves propagating in tissue. The goal of this study is to establish an ergonomically flexible passive-driver design for brain MRE, to evaluate the reproducibility of MRE tissue-stiffness measurements, and to investigate the relationship between tissue-stiffness measurements and driver frequencies. An ergonomically flexible passive pillow-like driver was designed to induce mechanical waves in the brain. Two-dimensional finite-element simulation was used to evaluate mechanical wave propagation patterns in brain tissues. MRE scans were performed on 10 healthy volunteers at mechanical frequencies of 60, 50, and 40 Hz. An axial mid-brain slice was acquired using an echo-planar imaging sequence to map the displacement pattern with the motion-encoding gradient along the through-plane (z) direction. All subjects were scanned and rescanned within 1 h. The Wilcoxon signed-rank test was used to test for differences between white matter and gray matter shear-stiffness values. One-way analysis of variance (ANOVA) was used to test for differences between shear-stiffness measurements made at different frequencies. Scan-rescan reproducibility was evaluated by calculating the within-subject coefficient of variation (CV) for each subject. The finite-element simulation showed that a pillow-like passive driver is capable of efficient shear-wave propagation through brain tissue. No subjects complained about discomfort during MRE acquisitions using the ergonomically designed driver. The white-matter elastic modulus (mean ±â€¯standard deviation) across all subjects was 3.85 ±â€¯0.12 kPa, 3.78 ±â€¯0.15 kPa, and 3.36 ±â€¯0.11 kPa at frequencies of 60, 50, and 40 Hz, respectively. The gray-matter elastic modulus across all subjects was 3.33 ±â€¯0.14 kPa, 2.82 ±â€¯0.16 kPa, and 2.24 ±â€¯0.14 kPa at frequencies of 60, 50, and 40 Hz, respectively. The Wilcoxon signed-rank test confirmed that the shear stiffness was significantly higher in white matter than gray matter at all three frequencies. The ranges of within-subject coefficients of variation for white matter, gray matter, and whole-brain shear-stiffness measurements for the three frequencies were 1.8-3.5% (60 Hz), 4.7-6.0% (50 Hz), and 3.7-4.1% (40 Hz). An ergonomic pneumatic pillow-like driver is feasible for highly reproducible in vivo evaluation of brain-tissue shear stiffness. Brain-tissue shear-stiffness values were frequency-dependent, thus emphasizing the importance of standardizing MRE acquisition protocols in multi-center studies.

Visualizing High-Order Decay after Disequilibria.

High-order decay equations are often difficult to study without significant care taken with variables and assumptions. As parent and progeny activities evolve over time, the effects of uncertainties and approximations confound the quality and interpretation of results. Of particular concern is the situation when decay equilibrium has been disturbed and progenies have arbitrary initial activities. To address this, code was created using Wolfram Mathematica to visualize the time-activity plots of the high order progenies of naturally occurring radioactive material after secular equilibrium is disturbed. The Bateman equation for an un-replenished parent was expanded to calculate activity vs. time for up to 13 progenies at different initial activities. The code uses the formula of Skrable et al., without parent production, expanded to the 13th progeny with arbitrary initial concentration. The code calculates and plots activity vs. time; it also reports the cumulative disintegrations of each progeny over a user-specified time period for comparison to counting measurements. The code could also be modified to incorporate additional production or branched decay schemes. We believe this code may be useful to health physicists and is intended to be accessible for anyone's use. This paper presents the code with explanations and examples on how to use it.

Absence of Myostatin Improves Cardiac Function Following Myocardial Infarction.

BACKGROUND: Myostatin inhibits the development of skeletal muscle and regulates the proliferation of skeletal muscle fibroblasts. However, the role of myostatin in regulating cardiac muscle or myofibroblasts, specifically in acute myocardial infarction (MI), is less clear. This study sought to determine whether absence of myostatin altered left ventricular function post-MI. METHODS: Myostatin-null mice (Mstn-/-) and wild-type (WT) mice underwent ligation of the left anterior descending artery to induce MI. Left ventricular function was measured at baseline, days 1 and 28 post-MI. Immunohistochemistry and immunofluorescence were obtained at day 28 for cellular proliferation, collagen deposition, and myofibroblastic activity. RESULTS: Whilst left ventricular function at baseline and size of infarct were similar, significant differences in favour of Mstn-/- compared to WT mice post-MI include a greater recovery of ejection fraction (61.8±1.1% vs 57.1±2.3%, p<0.01), less collagen deposition (41.9±2.8% vs 54.7±3.4%, p<0.05), and lower mortality (0 vs. 20%, p<0.05). There was no difference in the number of BrdU positive cells, percentage of apoptotic cardiomyocytes, or size of cardiomyocytes post-MI between WT and Mstn-/- mice. CONCLUSIONS: Absence of myostatin potentially protects the function of the heart post-MI with improved survival, possibly by limiting extent of fibrosis.

IGF1 stimulates greater muscle hypertrophy in the absence of myostatin in male mice.

Insulin-like growth factors (IGFs) and myostatin have opposing roles in regulating the growth and size of skeletal muscle, with IGF1 stimulating, and myostatin inhibiting, growth. However, it remains unclear whether these proteins have mutually dependent, or independent, roles. To clarify this issue, we crossed myostatin null (Mstn-/-) mice with mice overexpressing Igf1 in skeletal muscle (Igf1+) to generate six genotypes of male mice; wild type (Mstn+/+ ), Mstn+/-, Mstn-/-, Mstn+/+:Igf1+, Mstn+/-:Igf1+ and Mstn-/-:Igf1+ Overexpression of Igf1 increased the mass of mixed fibre type muscles (e.g. Quadriceps femoris) by 19% over Mstn+/+ , 33% over Mstn+/- and 49% over Mstn-/- (P < 0.001). By contrast, the mass of the gonadal fat pad was correspondingly reduced with the removal of Mstn and addition of Igf1 Myostatin regulated the number, while IGF1 regulated the size of myofibres, and the deletion of Mstn and Igf1+ independently increased the proportion of fast type IIB myosin heavy chain isoforms in T. anterior (up to 10% each, P < 0.001). The abundance of AKT and rpS6 was increased in muscles of Mstn-/-mice, while phosphorylation of AKTS473 was increased in Igf1+mice (Mstn+/+:Igf1+, Mstn+/-:Igf1+ and Mstn-/-:Igf1+). Our results demonstrate that a greater than additive effect is observed on the growth of skeletal muscle and in the reduction of body fat when myostatin is absent and IGF1 is in excess. Finally, we show that myostatin and IGF1 regulate skeletal muscle size, myofibre type and gonadal fat through distinct mechanisms that involve increasing the total abundance and phosphorylation status of AKT and rpS6.

Permanent-magnet energy spectrometer for electron beams from radiotherapy accelerators.

PURPOSE: The purpose of this work was to adapt a lightweight, permanent magnet electron energy spectrometer for the measurement of energy spectra of therapeutic electron beams. METHODS: An irradiation geometry and measurement technique were developed for an approximately 0.54-T, permanent dipole magnet spectrometer to produce suitable latent images on computed radiography (CR) phosphor strips. Dual-pinhole electron collimators created a 0.318-cm diameter, approximately parallel beam incident on the spectrometer and an appropriate dose rate at the image plane (CR strip location). X-ray background in the latent image, reduced by a 7.62-cm thick lead block between the pinhole collimators, was removed using a fitting technique. Theoretical energy-dependent detector response functions (DRFs) were used in an iterative technique to transform CR strip net mean dose profiles into energy spectra on central axis at the entrance to the spectrometer. These spectra were transformed to spectra at 95-cm source to collimator distance (SCD) by correcting for the energy dependence of electron scatter. The spectrometer was calibrated by comparing peak mean positions in the net mean dose profiles, initially to peak mean energies determined from the practical range of central-axis percent depth-dose (%DD) curves, and then to peak mean energies that accounted for how the collimation modified the energy spectra (recalibration). The utility of the spectrometer was demonstrated by measuring the energy spectra for the seven electron beams (7-20 MeV) of an Elekta Infinity radiotherapy accelerator. RESULTS: Plots of DRF illustrated their dependence on energy and position in the imaging plane. Approximately 15 iterations solved for the energy spectra at the spectrometer entrance from the measured net mean dose profiles. Transforming those spectra into ones at 95-cm SCD increased the low energy tail of the spectra, while correspondingly decreasing the peaks and shifting them to slightly lower energies. Energy calibration plots of peak mean energy versus peak mean position of the net mean dose profiles for each of the seven electron beams followed the shape predicted by the Lorentz force law for a uniform z-component of the magnetic field, validating its being modeled as uniform (0.542 ± 0.027 T). Measured Elekta energy spectra and their peak mean energies correlated with the 0.5-cm (7-13 MeV) and the 1.0-cm (13-20 MeV) R90 spacings of the %DD curves. The full-width-half-maximum of the energy spectra decreased with decreasing peak mean energy with the exception of the 9-MeV beam, which was anomalously wide. Similarly, R80-20 decreased linearly with peak mean energy with the exception of the 9 MeV beam. Both were attributed to suboptimal tuning of the high power phase shifter for the recycled radiofrequency power reentering the traveling wave accelerator. CONCLUSIONS: The apparatus and analysis techniques of the authors demonstrated that an inexpensive, lightweight, permanent magnet electron energy spectrometer can be used for measuring the electron energy distributions of therapeutic electron beams (6-20 MeV). The primary goal of future work is to develop a real-time spectrometer by incorporating a real-time imager, which has potential applications such as beam matching, ongoing beam tune maintenance, and measuring spectra for input into Monte Carlo beam calculations.

Translational signalling, atrogenic and myogenic gene expression during unloading and reloading of skeletal muscle in myostatin-deficient mice.

Skeletal muscles of myostatin null (Mstn(-/-)) mice are more susceptible to atrophy during hind limb suspension (HS) than are muscles of wild-type mice. Here we sought to elucidate the mechanism for this susceptibility and to determine if Mstn(-/-) mice can regain muscle mass after HS. Male Mstn(-/-) and wild-type mice were subjected to 0, 2 or 7 days of HS or 7 days of HS followed by 1, 3 or 7 days of reloading (n = 6 per group). Mstn(-/-) mice lost more mass from muscles expressing the fast type IIb myofibres during HS and muscle mass was recovered in both genotypes after reloading for 7 days. Concentrations of MAFbx and MuRF1 mRNA, crucial ligases regulating the ubiquitin-proteasome system, but not MUSA1, a BMP-regulated ubiquitin ligase, were increased more in muscles of Mstn(-/-) mice, compared with wild-type mice, during HS and concentrations decreased in both genotypes during reloading. Similarly, concentrations of LC3b, Gabarapl1 and Atg4b, key effectors of the autophagy-lysosomal system, were increased further in muscles of Mstn(-/-) mice, compared with wild-type mice, during HS and decreased in both genotypes during reloading. There was a greater abundance of 4E-BP1 and more bound to eIF4E in muscles of Mstn(-/-) compared with wild-type mice (P<0.001). The ratio of phosphorylated to total eIF2α increased during HS and decreased during reloading, while the opposite pattern was observed for rpS6. Concentrations of myogenic regulatory factors (MyoD, Myf5 and myogenin) mRNA were increased during HS in muscles of Mstn(-/-) mice compared with controls (P<0.001). We attribute the susceptibility of skeletal muscles of Mstn(-/-) mice to atrophy during HS to an up- and downregulation, respectively, of the mechanisms regulating atrophy of myofibres and translation of mRNA. These processes are reversed during reloading to aid a faster rate of recovery of muscle mass in Mstn(-/-) mice.

Accuracy and precision of cone-beam computed tomography guided intensity modulated radiation therapy.

PURPOSE: To assess the accuracy and precision of cone-beam computed tomography (CBCT)-guided intensity modulated radiation therapy (IMRT). METHODS AND MATERIALS: A 7-field intensity modulated radiation therapy plan was constructed for an anthropomorphic head phantom loaded with a custom cassette containing radiochromic film. The phantom was positioned on the treatment table at 9 locations: 1 "correct" position and 8 "misaligned" positions along 3 orthogonal axes. A commercial kilovoltage cone-beam computed tomography (kV-CBCT) system (VolumeView, Elekta AB, Stockholm, Sweden) was then used to align the phantom prior to plan delivery. The treatment plan was delivered using the radiation therapy delivery system (Infinity; Elekta AB) 3 times for each of the 9 positions, allowing film measurement of the delivered dose distribution in 3 orthogonal planes. Comparison of the planned and delivered dose profiles along the major axes provided an estimate of the accuracy and precision of CBCT-guided IMRT. RESULTS: On average, targeting accuracy was found to be within 1 mm in all 3 major anatomic planes. Over all 54 measured dose profiles, the means and standard errors of the displacement of the center of the field between the measured and calculated profiles for each of the right-left, anterior-posterior, and superior-inferior axes were +0.08 ± 0.07 mm, +0.60 ± 0.08 mm, and +0.78 ± 0.16 mm, respectively. Agreement between planned and measured 80% profiles was less than 0.4 mm on either side along the right-left axis. A systematic shift of the measured profile of slightly less than 1 mm in anterior and superior directions was noted along the anterior-posterior and superior-inferior axes, respectively. CONCLUSIONS: Submillimeter targeting accuracy can be achieved using a commercial kV-CBCT IGRT system.

Discovery of a mammalian splice variant of myostatin that stimulates myogenesis.

Myostatin plays a fundamental role in regulating the size of skeletal muscles. To date, only a single myostatin gene and no splice variants have been identified in mammals. Here we describe the splicing of a cryptic intron that removes the coding sequence for the receptor binding moiety of sheep myostatin. The deduced polypeptide sequence of the myostatin splice variant (MSV) contains a 256 amino acid N-terminal domain, which is common to myostatin, and a unique C-terminus of 65 amino acids. Western immunoblotting demonstrated that MSV mRNA is translated into protein, which is present in skeletal muscles. To determine the biological role of MSV, we developed an MSV over-expressing C2C12 myoblast line and showed that it proliferated faster than that of the control line in association with an increased abundance of the CDK2/Cyclin E complex in the nucleus. Recombinant protein made for the novel C-terminus of MSV also stimulated myoblast proliferation and bound to myostatin with high affinity as determined by surface plasmon resonance assay. Therefore, we postulated that MSV functions as a binding protein and antagonist of myostatin. Consistent with our postulate, myostatin protein was co-immunoprecipitated from skeletal muscle extracts with an MSV-specific antibody. MSV over-expression in C2C12 myoblasts blocked myostatin-induced Smad2/3-dependent signaling, thereby confirming that MSV antagonizes the canonical myostatin pathway. Furthermore, MSV over-expression increased the abundance of MyoD, Myogenin and MRF4 proteins (P<0.05), which indicates that MSV stimulates myogenesis through the induction of myogenic regulatory factors. To help elucidate a possible role in vivo, we observed that MSV protein was more abundant during early post-natal muscle development, while myostatin remained unchanged, which suggests that MSV may promote the growth of skeletal muscles. We conclude that MSV represents a unique example of intra-genic regulation in which a splice variant directly antagonizes the biological activity of the canonical gene product.

Photon counting spectral breast CT: effect of adaptive filtration on CT numbers, noise, and contrast to noise ratio.

PURPOSE: Photon counting spectral (PCS) computed tomography (CT) shows promise for breast imaging. An issue with current photon-counting detectors is low count rate capabilities, artifacts resulting from nonuniform count rate across the field of view, and suboptimal spectral information. These issues are addressed in part by using tissue-equivalent adaptive filtration of the x-ray beam. The purpose of the study was to investigate the effect of adaptive filtration on different aspects of PCS breast CT. METHODS: The theoretical formulation for the filter shape was derived for different filter materials and evaluated by simulation and an experimental prototype of the filter was fabricated from a tissue-like material (acrylic). The PCS CT images of a glandular breast phantom with adipose and iodine contrast elements were simulated at 40, 60, 90, and 120 kVp tube voltages, with and without adaptive filter. The CT numbers, CT noise, and contrast-to-noise ratio (CNR) were compared for spectral CT images acquired with and without adaptive filters. Similar comparison was made for material-decomposed PCS CT images. RESULTS: The adaptive filter improved the uniformity of CT numbers, CT noise, and CNR in both ordinary and material decomposed PCS CT images. At the same tube output the average CT noise with adaptive filter, although uniform, was higher than the average noise without adaptive filter due to x-ray absorption by the filter. Increasing tube output, so that average skin exposure with the adaptive filter was same as without filter, made the noise with adaptive filter comparable to or lower than that without adaptive filter. Similar effects were observed when energy weighting was applied, and when material decompositions were performed using energy selective CT data. CONCLUSIONS: An adaptive filter decreases count rate requirements to the photon counting detectors which enables PCS breast CT based on commercially available detector technologies. Adaptive filter also improves image quality in PCS breast CT by decreasing beam hardening artifacts and by eliminating spatial nonuniformities of CT numbers, noise, and CNR.

Dose-response curve of EBT, EBT2, and EBT3 radiochromic films to synchrotron-produced monochromatic x-ray beams.

PURPOSE: This work investigates the dose-response curves of GAFCHROMIC(®) EBT, EBT2, and EBT3 radiochromic films using synchrotron-produced monochromatic x-ray beams. EBT2 film is being utilized for dose verification in photoactivated Auger electron therapy at the Louisiana State University Center for Advanced Microstructures and Devices (CAMD) synchrotron facility. METHODS: Monochromatic beams of 25, 30, and 35 keV were generated on the tomography beamline at CAMD. Ion chamber depth-dose measurements were used to determine the dose delivered to films irradiated at depths from 0.7 to 8.5 cm in a 10 × 10 × 10-cm(3) polymethylmethacrylate phantom. AAPM TG-61 protocol was applied to convert measured ionization into dose. Films were digitized using an Epson 1680 Professional flatbed scanner and analyzed using the net optical density (NOD) derived from the red channel. A dose-response curve was obtained at 35 keV for EBT film, and at 25, 30, and 35 keV for EBT2 and EBT3 films. Calibrations of films for 4 MV x-rays were obtained for comparison using a radiotherapy accelerator at Mary Bird Perkins Cancer Center. RESULTS: The sensitivity (NOD per unit dose) of EBT film at 35 keV relative to that for 4-MV x-rays was 0.73 and 0.76 for doses 50 and 100 cGy, respectively. The sensitivity of EBT2 film at 25, 30, and 35 keV relative to that for 4-MV x-rays varied from 1.09-1.07, 1.23-1.17, and 1.27-1.19 for doses 50-200 cGy, respectively. For EBT3 film the relative sensitivity was within 3% of unity for all three monochromatic x-ray beams. CONCLUSIONS: EBT and EBT2 film sensitivity showed strong energy dependence over an energy range of 25 keV-4 MV, although this dependence becomes weaker for larger doses. EBT3 film shows weak energy dependence, indicating that it would be a better dosimeter for kV x-ray beams where beam hardening effects can result in large changes in the effective energy.

Verification of TG-61 dose for synchrotron-produced monochromatic x-ray beams using fluence-normalized MCNP5 calculations.

PURPOSE: Ion chamber dosimetry is being used to calibrate dose for cell irradiations designed to investigate photoactivated Auger electron therapy at the Louisiana State University Center for Advanced Microstructures and Devices (CAMD) synchrotron facility. This study performed a dosimetry intercomparison for synchrotron-produced monochromatic x-ray beams at 25 and 35 keV. Ion chamber depth-dose measurements in a polymethylmethacrylate (PMMA) phantom were compared with the product of MCNP5 Monte Carlo calculations of dose per fluence and measured incident fluence. METHODS: Monochromatic beams of 25 and 35 keV were generated on the tomography beamline at CAMD. A cylindrical, air-equivalent ion chamber was used to measure the ionization created in a 10 × 10 × 10-cm(3) PMMA phantom for depths from 0.6 to 7.7 cm. The American Association of Physicists in Medicine TG-61 protocol was applied to convert measured ionization into dose. Photon fluence was determined using a NaI detector to make scattering measurements of the beam from a thin polyethylene target at angles 30°-60°. Differential Compton and Rayleigh scattering cross sections obtained from xraylib, an ANSI C library for x-ray-matter interactions, were applied to derive the incident fluence. MCNP5 simulations of the irradiation geometry provided the dose deposition per photon fluence as a function of depth in the phantom. RESULTS: At 25 keV the fluence-normalized MCNP5 dose overestimated the ion-chamber measured dose by an average of 7.2 ± 3.0%-2.1 ± 3.0% for PMMA depths from 0.6 to 7.7 cm, respectively. At 35 keV the fluence-normalized MCNP5 dose underestimated the ion-chamber measured dose by an average of 1.0 ± 3.4%-2.5 ± 3.4%, respectively. CONCLUSIONS: These results showed that TG-61 ion chamber dosimetry, used to calibrate dose output for cell irradiations, agreed with fluence-normalized MCNP5 calculations to within approximately 7% and 3% at 25 and 35 keV, respectively.

Potential of discrete Gaussian edge feathering method for improving abutment dosimetry in eMLC-delivered segmented-field electron conformal therapy.

PURPOSE: The purpose of this work was to investigate the potential of discrete Gaussian edge feathering of the higher energy electron fields for improving abutment dosimetry in the planning volume when using an electron multileaf collimator (eMLC) to deliver segmented-field electron conformal therapy (ECT). METHODS: A discrete (five-step) Gaussian edge spread function was used to match dose penumbras of differing beam energies (6-20 MeV) at a specified depth in a water phantom. Software was developed to define the leaf eMLC positions of an eMLC that most closely fit each electron field shape. The effect of 1D edge feathering of the higher energy field on dose homogeneity was computed and measured for segmented-field ECT treatment plans for three 2D PTVs in a water phantom, i.e., depth from the water surface to the distal PTV surface varied as a function of the x-axis (parallel to leaf motion) and remained constant along the y-axis (perpendicular to leaf motion). Additionally, the effect of 2D edge feathering was computed and measured for one radially symmetric, 3D PTV in a water phantom, i.e., depth from the water surface to the distal PTV surface varied as a function of both axes. For the 3D PTV, the feathering scheme was evaluated for 0.1-1.0-cm leaf widths. Dose calculations were performed using the pencil beam dose algorithm in the Pinnacle(3) treatment planning system. Dose verification measurements were made using a prototype eMLC (1-cm leaf width). RESULTS: 1D discrete Gaussian edge feathering reduced the standard deviation of dose in the 2D PTVs by 34, 34, and 39%. In the 3D PTV, the broad leaf width (1 cm) of the eMLC hindered the 2D application of the feathering solution to the 3D PTV, and the standard deviation of dose increased by 10%. However, 2D discrete Gaussian edge feathering with simulated eMLC leaf widths of 0.1-0.5 cm reduced the standard deviation of dose in the 3D PTV by 33-28%, respectively. CONCLUSIONS: A five-step discrete Gaussian edge spread function applied in 2D improves the abutment dosimetry but requires an eMLC leaf resolution better than 1 cm.

Improved x-ray spectroscopy with room temperature CZT detectors.

Compact, room temperature x-ray spectroscopy detectors are of interest in many areas including diagnostic x-ray imaging, radiation protection and dosimetry. Room temperature cadmium zinc telluride (CZT) semiconductor detectors are promising candidates for these applications. One of the major problems for CZT detectors is low-energy tailing of the energy spectrum due to hole trapping. Spectral post-correction methods to correct the tailing effect do not work well for a number of reasons; thus it is advisable to eliminate the hole trapping effect in CZT using physical methods rather than correcting an already deteriorated energy spectrum. One method is using a CZT detector with an electrode configuration which modifies the electric field in the CZT volume to decrease low-energy tailing. Another method is to irradiate the CZT surface at a tilted angle, which modifies depth of interaction to decrease low-energy tailing. Neither method alone, however, eliminates the tailing effect. In this work, we have investigated the combination of modified electric field and tilted angle irradiation in a single detector to further decrease spectral tailing. A planar CZT detector with 10 × 10 × 3 mm³ size and CZT detector with 5 × 5 × 5 mm³ size and cap-shaped electrode were used in this study. The cap-shaped electrode (referred to as CAPture technology) modifies the electric field distribution in the CZT volume and decreases the spectral tailing effect. The detectors were investigated at 90° (normal) and 30° (tilted angle) irradiation modes. Two isotope sources with 59.6 and 122 keV photon energies were used for gamma-ray spectroscopy experiments. X-ray spectroscopy was performed using collimated beams at 60, 80 and 120 kVp tube voltages, in both normal and tilted angle irradiation. Measured x-ray spectra were corrected for K x-ray escape fractions that were calculated using Monte Carlo methods. The x-ray spectra measured with tilted angle CAPture detector at 60, 80 and 120 kVp tube voltages were compared to corresponding theoretical spectra. The low-energy tailing was nearly completely eliminated from 59.6 and 122 keV isotope spectra, and 60, 80 and 120 kVp x-ray spectra, when CAPture detector was used with 30° tilted angle irradiation. It is concluded that using a CZT detector with modified electric field in tilted angle configuration resolves problem of the tailing effect in CZT detectors, opening promising possibilities in gamma-ray and x-ray spectroscopy applications.

Intravascular imaging with a storage phosphor detector.

The aim of this study is to develop and test an intravascular positron imaging system based on a storage phosphor detector for imaging and detecting vulnerable plaques of human coronary arteries. The radiotracer F18-FDG accumulates in vulnerable plaques with inflammation of the overlying cap. The vulnerable plaques can, therefore, be imaged by recording positrons emitted from F18-FDG with a detector inserted into the artery. A prototype intravascular detector was constructed based on storage phosphor. The detector uses a flexible storage phosphor tube with 55 mm length, 2 mm diameter and 0.28 mm wall thickness. The intravascular detector is guided into the vessel using x-ray fluoroscopy and the accumulated x-ray signal must be erased prior to positron imaging. For this purpose, a light diffuser, 0.9 mm in diameter and 55 mm in length, was inserted into the detector tube. The light diffuser was connected to a laser source through a 2 m long optical fiber. The diffuser redirected the 0.38 W laser light to the inner surface of the phosphor detector to erase it. A heart phantom with 300 cm(3) volume and three coronary arteries with 3.2 mm diameter and with several plaques was constructed. FDG solution with 0.5 microCi cm(-3) activity concentration was filled in the heart and coronary arteries. The detector was inserted in a coronary artery and the signal from the plaques and surrounding background activity was recorded for 2 min. Then the phosphor detector was extracted and read out using a storage phosphor reader. The light diffuser erased the signal resulting from fluoroscopic exposure to level below that encountered during positron imaging. Vulnerable plaques with area activities higher than 1.2 nCi mm(-2) were visualized by the detector. This activity is a factor of 10-20 lower than that expected in human vulnerable plaques. The detector was able to image the internal surface of the coronary vessels with 50 mm length and 360 degrees circumference. Spatial resolution was 0.6-1.2 mm FWHM with a readout pixel resolution of 80 microm. The detector is flexible, reusable and easy to handle; it provides virtually real-time imaging. An intravascular imaging detector based on storage phosphor has shown a potential for imaging human coronary artery plaques. The detector provides the sensitivity, spatial resolution, flexibility and short imaging times necessary for clinical applications. Future research will decrease the detector diameter from 2 mm to 1 mm, and will apply the design to in vivo animal experiments.

The structure of the cornified claw sheath in the domesticated cat (Felis catus): implications for the claw-shedding mechanism and the evolution of cornified digital end organs.

The morphology of cornified structures is notoriously difficult to analyse because of the extreme range of hardness of their component tissues. Hence, a correlative approach using light microscopy, scanning electron microscopy, three-dimensional reconstructions based on x-ray computed tomography data, and graphic modeling was applied to study the morphology of the cornified claw sheath of the domesticated cat as a model for cornified digital end organs. The highly complex architecture of the cornified claw sheath is generated by the living epidermis that is supported by the dermis and distal phalanx. The latter is characterized by an ossified unguicular hood, which overhangs the bony articular base and unguicular process of the distal phalanx and creates an unguicular recess. The dermis covers the complex surface of the bony distal phalanx but also creates special structures, such as a dorsal dermal papilla that points distally and a curved ledge on the medial and lateral sides of the unguicular process. The hard-cornified external coronary horn and proximal cone horn form the root of the cornified claw sheath within the unguicular recess, which is deeper on the dorsal side than on the medial and lateral sides. As a consequence, their rate of horn production is greater dorsally, which contributes to the overall palmo-apical curvature of the cornified claw sheath. The external coronary and proximal cone horn is worn down through normal use as it is pushed apically. The hard-cornified apical cone horn is generated by the living epidermis enveloping the base and free part of the dorsal dermal papilla. It forms nested horn cones that eventually form the core of the hardened tip of the cornified claw. The sides of the cornified claw sheath are formed by the newly described hard-cornified blade horn, which originates from the living epidermis located on the slanted face of the curved ledge. As the blade horn is moved apically, it entrains and integrates the hard-cornified parietal horn on its internal side. It is covered by the external coronary and proximal cone horn on its external side. The soft-cornified terminal horn extends distally from the parietal horn and covers the dermal claw bed at the tip of the uniguicular process, thereby filling the space created by the converging apical cone and blade horn. The soft-cornified sole horn fills the space between the cutting edges of blade horn on the palmar side of the cornified claw sheath. The superficial soft-cornified perioplic horn is produced on the internal side of the unguicular pleat, which surrounds the root of the cornified claw sheath. The shedding of apical horn caps is made possible by the appearance of microcracks in the superficial layers of the external coronary and proximal cone horn in the course of deformations of the cornified claw sheath, which is subjected to tensile forces during climbing or prey catching. These microcracks propagate tangentially through the coronary horn and do not injure the underlying living epidermal and dermal tissues. This built-in shedding mechanism maintains sharp claw tips and ensures the freeing of the claws from the substrate.

Botulinum toxin-induced paralysis leads to slower myosin heavy chain isoform composition and reduced titin content in juvenile rat gastrocnemius muscle.

Intramuscular injections of botulinum toxin A (Btx-A) and exercise are used in the treatment of muscle spasticity in children with cerebral palsy. However, little is known about the biological changes within muscle subsequent to Btx-A-induced paralysis and how the combination of Btx-A and exercise might affect the growing muscle. The wet mass, myosin heavy chain (MHC) composition, and titin content of the juvenile rat gastrocnemius muscle were determined 3 weeks after Btx-A injections and subsequent voluntary wheel-running exercise. Btx-A increased the proportion of type IIa (+121%) and IIx (+65%) MHC while decreasing the proportion of type IIb MHC (-51%) and reducing the titin content (-18%). Exercise did not amplify or reduce the changes induced by Btx-A. Thus, we conclude that although the sarcomeric stability of paralyzed muscle might be impaired, moderate mechanical loading does not seem to affect paralyzed muscle protein composition.