High-energy proton imaging for biomedical applications.

The charged particle community is looking for techniques exploiting proton interactions instead of X-ray absorption for creating images of human tissue. Due to multiple Coulomb scattering inside the measured object it has shown to be highly non-trivial to achieve sufficient spatial resolution. We present imaging of biological tissue with a proton microscope. This device relies on magnetic optics, distinguishing it from most published proton imaging methods. For these methods reducing the data acquisition time to a clinically acceptable level has turned out to be challenging. In a proton microscope, data acquisition and processing are much simpler. This device even allows imaging in real time. The primary medical application will be image guidance in proton radiosurgery. Proton images demonstrating the potential for this application are presented. Tomographic reconstructions are included to raise awareness of the possibility of high-resolution proton tomography using magneto-optics.

Ion beam tracking using ultrasound motion detection.

PURPOSE: The use of motion mitigation techniques such as tracking and gating in particle therapy requires real-time knowledge of tumor position with millimeter precision. The aim of this phantom-based study was to evaluate the option of diagnostic ultrasound (US) imaging (sonography) as real-time motion detection method for scanned heavy ion beam irradiation of moving targets. METHODS: For this pilot experiment, a tumor surrogate was moved inside a water bath along two-dimensional trajectories. A rubber ball was used for this purpose. This ball was moved by a robotic arm in two dimensions lateral to the heavy ion beam. Trajectories having a period of 3 s and peak to peak amplitude of 20 mm were used. Square radiation fields of[Formula: see text] were irradiated on radiosensitive films with a 200 MeV/u beam of calcium ions having a FWHM of 6 mm. Pencil beam scanning and beam tracking were employed. The films were attached on the robotic arm and thus moved with the rubber ball. The position of the rubber ball was continuously measured by a US tracking system (Mediri GmbH, Heidelberg) and sent to the GSI therapy control system (TCS). This position was used as tracking vector. Position reconstruction from the US tracking system and data communication introduced a delay leading to a position error of several millimeters. An artificial neural network (ANN) was implemented in the TCS to predict motion from US measurements and thus to compensate for the delay. RESULTS: Using ANN delay compensation and large motion amplitudes, the authors could produce irradiation patterns with a few percent inhomogeneity and about 1 mm geometrical conformity. CONCLUSIONS: This pilot experiment suggests that diagnostic US should be further investigated as dose-free, high frame-rate, and model-independent motion detection method for scanning heavy ion beam irradiation of moving targets.

Ultrasound tracking for intra-fractional motion compensation in radiation therapy.

Modern techniques as ion beam therapy or 4D imaging require precise target position information. However, target motion particularly in the abdomen due to respiration or patient movement is still a challenge and demands methods that detect and compensate this motion. Ultrasound represents a non-invasive, dose-free and model-independent alternative to fluoroscopy, respiration belt or optical tracking of the patient surface. Thus, ultrasound based motion tracking was integrated into irradiation with actively scanned heavy ions. In a first in vitro experiment, the ultrasound tracking system was used to compensate diverse sinusoidal target motions in two dimensions. A time delay of ∼200 ms between target motion and reported position data was compensated by a prediction algorithm (artificial neural network). The irradiated films proved feasibility of the proposed method. Furthermore, a practicable and reliable calibration workflow was developed to enable the transformation of ultrasound tracking data to the coordinates of the treatment delivery or imaging system - even if the ultrasound probe moves due to respiration. A first proof of principle experiment was performed during time-resolved positron emission tomography (4DPET) to test the calibration workflow and to show the accuracy of an ultrasound based motion tracking in vitro. The results showed that optical ultrasound tracking can reach acceptable accuracies and encourage further research.

Surface damage analysis of retrieved highly crosslinked polyethylene tibial components after short-term implantation.

The use of highly crosslinked polyethylene (PE) in the knee remains controversial, because of reduced fatigue fracture properties of the material. The current study investigated postmelt surface damage as well as potential contributors to this damage in retrieved highly crosslinked PE tibial components, after short-term in vivo durations. Retrieved conventional PE tibial components were examined for comparison, as well as unused time zero highly crosslinked and conventional PE tibial components for inherent manufacturing surface characterization. Predominant surface damage modes on highly crosslinked PE components were machine mark loss and abrasion, while conventional PE components primarily had machine mark loss, abrasion, and delamination. In vivo duration, PE thickness, and conformity of the design were significant predictors of surface damage on retrieved conventional PE components. Donor weight and the conformity of the design were significant predictors of surface damage on retrieved highly crosslinked PE components. This retrieval data on highly crosslinked PE tibial components suggest that in vivo wear occurred, observed as postmelt surface damage. The highly crosslinked Durasul material examined in this retrieval study appeared to outperform the conventional PE components made from 4150 resin, ram-extruded and gamma-sterilized in air, but not the conventional components made from 1020 resin, compression molding and gamma sterilization in nitrogen. Early retrieval data of highly crosslinked PE tibial components are important to serve as a benchmark to be compared with future longer-term retrieval studies investigating whether surface damage translates to clinically relevant particulate wear debris generation and PE clinical performance.

Examining the influence of short-term implantation on oxidative degradation in retrieved highly crosslinked polyethylene tibial components.

Concerns remain regarding the oxidative resistance of highly crosslinked polyethylene (PE). The study investigated the in vivo performance of Durasul highly crosslinked PE by comparing the oxidation index, density, and percent crystallinity in the weightbearing and nonweightbearing region of retrieved components with unused time zero tibial components. Retrieved and unused Sulene conventional PE tibial components were examined for comparison and the effects of shelf age, in vivo duration, and ex vivo duration were also investigated. The oxidation index was not significantly different between unused time zero and retrieved Durasul PE components. Regression analysis data supported these findings in that neither shelf age, in vivo duration, nor ex vivo duration was a significant predictor of oxidation index in the retrieved Durasul PE components. In contrast, the retrieved conventional PE components had significantly greater oxidation index, density, and percent crystallinity compared with unused time zero PE components. Regression data suggested that in vivo and ex vivo duration, but not shelf aging, influenced the changes observed in the conventional PE components. These data also showed that in vivo loading did not significantly affect the oxidation index, density, or percent crystallinity in either the retrieved Durasul or conventional PE tibial components. This investigation demonstrates that changes in oxidation index, density, and percent crystallinity of retrieved Durasul PE components after short-term in vivo durations are likely not a clinical concern. These data should be used as a benchmark to compare with future studies examining the long-term oxidative resistance of Durasul highly crosslinked PE tibial components.

The cyclization of parent and cyclic hexa-1,3-dien-5-ynes--a combined theoretical and experimental study.

The thermal cycloisomerization of both parent and benzannelated hexa-1,3-dien-5-yne, as well as of carbocyclic 1,3-dien-5-ynes (ring size 7-14), was investigated by using pure density functional theory (DFT) of Becke, Lee, Yang, and Parr (BLYP) in connection with the 6-31G* basis set and the Brueckner doubles coupled-cluster approach [BCCD(T)] with the cc-pVDZ basis set for the parent system. The initial cyclization product is the allenic cyclohexa-1,2,4-triene (isobenzene), while the respective biradical is the transition structure for the enantiomerization of the two allenes. Two consecutive [1,2]-H shifts further transform isobenzene to benzene. For the benzannelated system, the energetics are quite similar and the reaction path is the same with one exception: the intermediate biradical is not a transition state but a minimum which is energetically below isonaphthalene. The cyclization of the carbocyclic 1,3-dien-5-ynes, which follows the same reaction path as the parent system, clearly depends on the ring size. Like the cyclic enediynes, the dienynes were found to cyclize to products with reduced ring strain. This is not possible for the 7- and 8-membered dienynes, as their cyclization products are also highly strained. For 9- to 11-membered carbocycles, all intermediates, transition states, and products lie energetically below the parent system; this indicates a reduced cyclization temperature. All other rings (12- to 14-membered) have higher barriers. Exploratory kinetic experiments on the recently prepared 10- to 14-membered 1,3-dien-5-ynes rings show this tendency, and 10- and 11-membered rings indeed cyclize at lower temperatures.

Carbonyl- and carboxyl-substituted enediynes: synthesis, computations, and thermal reactivity.

The influence of electron-withdrawing groups (carbonyl and carboxyl) at the alkyne termini on the reactivity of enediynes was investigated by a combination of experimental and computational techniques. While the general chemical reactivity of such enediynes, especially if non-benzannelated, is increased markedly, the thermal cyclization, giving rise to Bergman cyclization products, is changed little relative to the parent enediyne system. This is evident from kinetic measurements and from density functional theory (DFT, BLYP/6-31G + thermal corrections) computations of the experimental systems which show that the Bergman cyclization barriers slightly (3-4 kcal/mol) increase, in contrast to earlier theoretical predictions. The effect on the endothermicities is large (DeltaDeltaH(r) = 7-12 kcal/mol). Hence, the increased reactivity of the substituted enediynes is entirely due to nucleophiles or radicals present in solution. This was demonstrated by quantitative experiments with diethylamine and tetramethyl piperidyl oxide (TEMPO) which both give fulvenes through 5-exo-dig cyclizations.