SU-E-T-187: Clinical Use of the Software for the Automation of Treatment Field Parameters Verification Prior to Radiation Delivery.

PURPOSE: Verification of treatment field parameters by therapists take place prior to every or first fraction. Such verification or field timeout should be completely independent from record-and-verify system. It is performed manually via reading treatment parameters from linac screen and comparing them to treatment plan. We evaluate clinical use of software allowing automation of field timeout. METHODS: The program for automated timeout performs three tasks.Plan information is extracted from PDF printouts generated by Eclipse (Varian Medical Systems, Palo Alto, CA) treatment planning system. User selects patient, plan and field to be compared with the field moded-up at the linac. Information from the Varian (Varian Medical Systems) linac's screen is extracted using video signal splitter and VGA2USB converter (Epiphan Systems, Ottawa, CA). Image farther undergoes character recognition, which works reliably for 1X, Trilogy and 2100C linacs used in out tests.The plan and linac screen information are output to the computer screen and user is alerted if mismatch is observed. The software uses tolerances established in out clinic. The program also outputs auxiliary information, e.g. bolus, which is not well alerted by or can be omitted in the record and verify system. In the workflow tested, PDF printouts are uploaded for the software during second check and automatic timeout is performed for all treatments except v-sim and first fraction (of each treatment plan). RESULTS: The software has friendly user interface and is easily included in clinical work flow. With the error rate being extremely low, we don't have data yet to claim that automated timeout provides higher safety than manual; however, it definitely cuts timeout time to 2-3sec per fields versus 10sec, if done manually. CONCLUSIONS: Field timeout automation is practicable and fits well into clinical workflow. It improves patient throughput and is expected to improve patient safety. CONFLICT OF INTEREST: S. Kriminski and I. Lysiuk: provisional patent application is submitted to United States Patent and Trademark Office.

SU-E-T-192: Computer Vision for Final Online Treatment Parameter Verification.

PURPOSE: In a typical model of Radiation Oncology data flow, treatment plan is designed on treatment planning station (TPS) under the supervision of physician and physicist, and machine specific parameters are pushed to Record and Verify system (RV) for treatment data storage, where it stays available for daily uploads to treatment station. While various QA programs could be established to verify uncorrupted planning data storage and transfer, the ultimate goal is a daily confirmation of patient treatment parameters versus original treatment plan. METHODS: A new computer vision approach, RTcheck, is used to digitize loaded machine parameters directly from the screen of Varian Clinical Console every time before the beam is turned on by a therapist. The verification engine runs a check against the parameters automatically extracted from the printed postscript planning report (Pinnacle, Philips) prepared during planning stage and approved by physician. All important beam data, MUs, jaws position, beam energy, couch angle, and wedge specifiers are displayed side by side on the screen of RTcheck station. All field verifications are recorded to a log file, periodically reviewed by a physicist. RESULTS: In our clinical tests, the electronic verification of machine treatment parameters shortened patient 'on the table' time, as the manual therapist's 'time out' check before every beam on may take up to several minutes for patient treatments with multiple beams (more than 10). Our analysis of verification logs revealed several instances of a small X1 jaw position discrepancy of 0.1cm for jaw position range of 0 to -2cm. After jaw recalibration, the problem was eliminated. CONCLUSIONS: RTcheck is the end-to-end quality assurance approach to verify data flow from TPS to treatment machine for every patient treatment. Computer vision approach may help reduce human error factor, and shorten patient treatment time. CONFLICT OF INTEREST: S. Kriminski and I. Lysiuk: provisional patent application is submitted to United States Patent and Trademark Office.

Sound velocity and elasticity of tetragonal lysozyme crystals by Brillouin spectroscopy.

Quasilongitudinal sound velocities and the second-order elastic moduli of tetragonal hen egg-white lysozyme crystals were determined as a function of relative humidity (RH) by Brillouin scattering. In hydrated crystals the measured sound velocities in the [110] plane vary between 2.12 +/- 0.03 km/s along the [001] direction and 2.31 +/- 0.08 km/s along the [110] direction. Dehydration from 98% to 67% RH increases the sound velocities and decreases the velocity anisotropy in (110) from 8.2% to 2.0%. A discontinuity in velocity and an inversion of the anisotropy is observed with increasing dehydration providing support for the existence of a structural transition below 88% RH. Brillouin linewidths can be described by a mechanical model in which the phonon is coupled to a relaxation mode of hydration water with a single relaxation time of 55 +/- 5 ps. At equilibrium hydration (98% RH) the longitudinal moduli C(11) + C(12) + 2C(66) = 12.81 +/- 0.08 GPa, C(11) = 5.49 +/- 0.03 GPa, and C(33) = 5.48 +/- 0.05 GPa were directly determined. Inversion of the measured sound velocities in the [110] plane constrains the combination C(44) + (1/2)C(13) to 2.99 +/- 0.05 GPa. Further constraints on the elastic tensor are obtained by combining the Brillouin quasilongitudinal results with axial compressibilities determined from high-pressure x-ray diffraction. We constrain the adiabatic bulk modulus to the range 2.7-5.3 GPa.

Heat transfer from protein crystals: implications for flash-cooling and X-ray beam heating.

Three problems involving heat transfer from a protein crystal to a cooling agent are analyzed: flash-cooling in a cold nitrogen- or helium-gas stream, plunge-cooling into liquid nitrogen, propane or ethane and crystal heating in a cold gas stream owing to X-ray absorption. Heat transfer occurs by conduction inside the crystal and by convection from the crystal's outer surface to the cooling fluid. For flash-cooling in cold gas streams, heat transfer is limited by the rate of external convection; internal temperature gradients and crystal strains during cooling are very small. Helium gas provides only a threefold improvement in cooling rates relative to nitrogen because its much larger thermal conductivity is offset by its larger kinematic viscosity. Characteristic cooling times vary with crystal size L as L(3/2) and theoretical estimates of these times are consistent with experiments. Plunge-cooling into liquid cryogens, which can give much smaller convective thermal resistances provided that surface boiling is eliminated, can increase cooling rates by more than an order of magnitude. However, the internal conduction resistance is no longer negligible, producing much larger internal temperature gradients and strains that may damage larger crystals. Based on this analysis, factors affecting the success of flash-cooling experiments can be ordered from most to least important as follows: (1) crystal solvent content and solvent composition, (2) crystal size and shape, (3) amount of residual liquid around the crystal, (4) cooling method (liquid plunge versus gas stream), (5) choice of gas/liquid and (6) relative speed between cooling fluid and crystal. Crystal heating by X-ray absorption on present high-flux beamlines should be small. For a fixed flux and illuminated area, heating can be reduced by using crystals with areas normal to the beam that are much larger than the beam area.

Flash-cooling and annealing of protein crystals.

Flash-cooling and annealing of macromolecular crystals have been investigated using in situ X-ray imaging, diffraction-peak lineshape measurements and conventional crystallographic diffraction. The dominant mechanisms by which flash-cooling creates disorder are suggested and a fixed-temperature annealing protocol for reducing this disorder is demonstrated that should be more reliable and flexible than existing protocols. Flash-cooling tetragonal lysozyme crystals degrades diffraction resolution and broadens the distributions of lattice orientations (mosaicity) and lattice spacings. The diffraction resolution strongly correlates with the width of the lattice-spacing distribution. Annealing at fixed temperatures of 253 and 233 K consistently reduces the lattice-spacing spread and improves the resolution for annealing times up to approximately 30s. X-ray images show that this improvement arises from the formation of well ordered domains with characteristic sizes >10 microm and narrower mosaicities than the crystal as a whole. Flash-cooled triclinic crystals of lysozyme, which have a smaller water content than the tetragonal form, diffract to higher resolution with smaller mosaicities and exhibit pronounced ordered domain structure even before annealing. It is suggested that differential thermal expansion of the protein lattice and solvent may be the primary cause of flash-cooling-induced disorder. Mechanisms by which annealing at T << 273 K reduce this disorder are discussed.

Dynamic response of tetragonal lysozyme crystals to changes in relative humidity: implications for post-growth crystal treatments.

The dynamic response of tetragonal lysozyme crystals to dehydration has been characterized in situ using a combination of X-ray topography, high-resolution diffraction line-shape measurements and conventional crystallographic diffraction. For dehydration from 98% relative humidity (r.h.) to above 89%, mosaicity and diffraction resolution show little change and X-ray topographs remain featureless. Lattice constants decrease rapidly but the lattice-constant distribution within the crystal remains very narrow, indicating that water concentration gradients remain very small. Near 88% r.h., the c-axis lattice parameter decreases abruptly, the steady-state mosaicity and diffraction resolution degrade sharply and topographs develop extensive contrast. This transformation exhibits metastability and hysteresis. At fixed r.h. < 88% it is irreversible, but the original order can be almost completely restored by rehydration. These results suggest that this transformation is a first-order structural transition involving an abrupt loss of crystal water. The front between transformed and untransformed regions may propagate inward from the crystal surface and the resulting stresses along the front may degrade mosaicity. Differences in crystal size, shape and initial perfection may produce the observed variations in degradation timescale. Consequently, the success of more general post-growth treatments may often involve identifying procedures that either avoid lattice transitions, minimize disorder created during such transitions or maintain the lattice in an ordered metastable state.

Macromolecular impurities and disorder in protein crystals.

The mechanisms by which macromolecular impurities degrade the diffraction properties of protein crystals have been investigated using X-ray topography, high-resolution diffraction line shape measurements, crystallographic data collection, chemical analysis, and two-photon excitation fluorescence microscopy. Hen egg-white lysozyme crystals grown from solutions containing a structurally unrelated protein (ovotransferrin) and a related protein (turkey egg-white lysozyme) can exhibit significantly broadened mosaicity due to formation of cracks and dislocations but have overall B factors and diffraction resolutions comparable to those of crystals grown from uncontaminated lysozyme. Direct fluorescence imaging of the three-dimensional impurity distribution shows that impurities incorporate with different densities in sectors formed by growth on different crystal faces, and that impurity densities in the crystal core and along boundaries between growth sectors can be much larger than in other parts of the crystal. These nonuniformities create stresses that drive formation of the defects responsible for the mosaic broadening. Our results provide a rationale for the use of seeding to obtain high-quality crystals from heavily contaminated solutions and have implications for the use of crystallization for protein purification. Proteins 1999;36:270-281.