The effect of Photon Activation Therapy on cisplatin pre-treated human tumour cell lines: comparison with conventional X-ray irradiation.

Cisplatin is an antineoplastic drug widely used for the treatment of several solid tumours. However, the side effects related to cisplatin-based anticancer therapy often outweigh the benefits. Therefore, the identification of new anticancer strategies able to offer a better toxicity profile while maintaining the same level of efficacy as platinum-based treatments would be highly desirable. We assessed the efficacy of synchrotron radiation in triggering the Auger effect in human A549 non-small cell lung cancer and IGROV-1 ovarian cancer cells pre-treated with cisplatin. Cisplatin was chosen as the carrier of platinum atoms in the cells because of its alkylating-like activity and the irradiation was done with monochromatic beams above and below the platinum K-shell edge (78.39 keV). On cisplatin-treated cells, at concentrations allowing 80 percent of cell survival with respect to controls, no differences were observed in cell viability when they were irradiated either above or below the K-shell edge of platinum, suggesting that cisplatin toxicity can mask the enhancement of cell death induced by the irradiation. At lower cisplatin concentrations allowing 95-90 percent of cell survival, an enhancement in cellular death with respect to conventional irradiation conditions was clearly observed in all cancer types when cells were irradiated with beams either above or below the platinum K-shell edge. Our results lend additional support to the suggestion that the Photon Activation Therapy in combination with cisplatin treatment should be further explored in relevant in vivo models of glioma and non-glioma cancer models.

Sound velocities in iron to 110 gigapascals.

The dispersion of longitudinal acoustic phonons was measured by inelastic x-ray scattering in the hexagonal closed-packed (hcp) structure of iron from 19 to 110 gigapascals. Phonon dispersion curves were recorded on polycrystalline iron compressed in a diamond anvil cell, revealing an increase of the longitudinal wave velocity (VP) from 7000 to 8800 meters per second. We show that hcp iron follows a Birch law for VP, which is used to extrapolate velocities to inner core conditions. Extrapolated longitudinal acoustic wave velocities compared with seismic data suggest an inner core that is 4 to 5% lighter than hcp iron.

Life sciences: microorganisms in the space environment.

Preliminary results of the Spacelab 1 experiment on the response of Bacillus subtilis spores to conditions of free space are presented. Exposure to the vacuum of space on the Spacelab pallet reduced viability counts about 50 percent and increased mutation frequencies by a factor of about 10. Interpretation of apparent differences in the photobiological and photochemical data between flight and ground simulation experiments will require more statistical analyses and data from actual fluence measurements.

Biological equivalent dose studies for dose escalation in the stereotactic synchrotron radiation therapy clinical trials.

Synchrotron radiation is an innovative tool for the treatment of brain tumors. In the stereotactic synchrotron radiation therapy (SSRT) technique a radiation dose enhancement specific to the tumor is obtained. The tumor is loaded with a high atomic number (Z) element and it is irradiated in stereotactic conditions from several entrance angles. The aim of this work was to assess dosimetric properties of the SSRT for preparing clinical trials at the European Synchrotron Radiation Facility (ESRF). To estimate the possible risks, the doses received by the tumor and healthy tissues in the future clinical conditions have been calculated by using Monte Carlo simulations (PENELOPE code). The dose enhancement factors have been determined for different iodine concentrations in the tumor, several tumor positions, tumor sizes, and different beam sizes. A scheme for the dose escalation in the various phases of the clinical trials has been proposed. The biological equivalent doses and the normalized total doses received by the skull have been calculated in order to assure that the tolerance values are not reached.

Survival of rats bearing advanced intracerebral F 98 tumors after glutathione depletion and microbeam radiation therapy: conclusions from a pilot project.

BACKGROUND: Resistance to radiotherapy is frequently encountered in patients with glioblastoma multiforme. It is caused at least partially by the high glutathione content in the tumour tissue. Therefore, the administration of the glutathione synthesis inhibitor Buthionine-SR-Sulfoximine (BSO) should increase survival time. METHODS: BSO was tested in combination with an experimental synchrotron-based treatment, microbeam radiation therapy (MRT), characterized by spatially and periodically alternating microscopic dose distribution. One hundred thousand F98 glioma cells were injected into the right cerebral hemisphere of adult male Fischer rats to generate an orthotopic small animal model of a highly malignant brain tumour in a very advanced stage. Therapy was scheduled for day 13 after tumour cell implantation. At this time, 12.5% of the animals had already died from their disease. The surviving 24 tumour-bearing animals were randomly distributed in three experimental groups: subjected to MRT alone (Group A), to MRT plus BSO (Group B) and tumour-bearing untreated controls (Group C). Thus, half of the irradiated animals received an injection of 100 µM BSO into the tumour two hours before radiotherapy. Additional tumour-free animals, mirroring the treatment of the tumour-bearing animals, were included in the experiment. MRT was administered in bi-directional mode with arrays of quasi-parallel beams crossing at the tumour location. The width of the microbeams was ≈28 µm with a center-to-center distance of ≈400 µm, a peak dose of 350 Gy, and a valley dose of 9 Gy in the normal tissue and 18 Gy at the tumour location; thus, the peak to valley dose ratio (PVDR) was 31. RESULTS: After tumour-cell implantation, otherwise untreated rats had a mean survival time of 15 days. Twenty days after implantation, 62.5% of the animals receiving MRT alone (group A) and 75% of the rats given MRT + BSO (group B) were still alive. Thirty days after implantation, survival was 12.5% in Group A and 62.5% in Group B. There were no survivors on or beyond day 35 in Group A, but 25% were still alive in Group B. Thus, rats which underwent MRT with adjuvant BSO injection experienced the largest survival gain. CONCLUSIONS: In this pilot project using an orthotopic small animal model of advanced malignant brain tumour, the injection of the glutathione inhibitor BSO with MRT significantly increased mean survival time.

Technology solutions for better outcomes: integrated information management in key to productivity increases in medicine.

The challenges to healthcare systems around the world are primarily impacted by two topics: demographic factors and progress in medicine. An ageing population inherently needs more medical services which add financial burdens, in particular, to public healthcare. Since the level of medical education is growing at the same time, we are observing an increased demand for sophisticated (in general expensive) medicine. Drastic changes in financing seem unavoidable. Multiple diagnoses, repeated examinations, trial-and-error, overcapacities and other signs of missing economical considerations are reinforced by reimbursement systems. In a world where, in principle, all information is available everywhere, more than a patient's history should be accessible. Other industries have knowledge management systems in place that make state-of-the-art expertise available everywhere. Intelligent patient databases could consist of learning cycles that (i) enable the individual to benefit from structured knowledge, in addition to personal experience of the physician, and (ii) use the knowledge generated from the individual to extend the database. The novel area of molecular medicine fits perfectly well into these scenarios. Only attached to an IT backbone can the flood of information be managed in a beneficial way. Efficiency improvements in healthcare address the needs of all parties in the system: patients, providers, and payers. The opportunities, however, can only materialize if everyone is prepared to change. IT will set the standards for the biggest challenge in healthcare: The paradigm shift in medicine.

In-line phase-contrast breast tomosynthesis: a phantom feasibility study at a synchrotron radiation facility.

The major objective is to adopt, apply and test developed in-house algorithms for volumetric breast reconstructions from projection images, obtained in in-line phase-contrast mode. Four angular sets, each consisting of 17 projection images obtained from four physical phantoms, were acquired at beamline ID17, European Synchroton Radiation Facility, Grenoble, France. The tomosynthesis arc was ±32°. The physical phantoms differed in complexity of texture and introduced features of interest. Three of the used phantoms were in-house developed, and made of epoxy resin, polymethyl-methacrylate and paraffin wax, while the fourth phantom was the CIRS BR3D. The projection images had a pixel size of 47 µm × 47 µm. Tomosynthesis images were reconstructed with standard shift-and-add (SAA) and filtered backprojection (FBP) algorithms. It was found that the edge enhancement observed in planar x-ray images is preserved in tomosynthesis images from both phantoms with homogeneous and highly heterogeneous backgrounds. In case of BR3D, it was found that features not visible in the planar case were well outlined in the tomosynthesis slices. In addition, the edge enhancement index calculated for features of interest was found to be much higher in tomosynthesis images reconstructed with FBP than in planar images and tomosynthesis images reconstructed with SAA. The comparison between images reconstructed by the two reconstruction algorithms shows an advantage for the FBP method in terms of better edge enhancement. Phase-contrast breast tomosynthesis realized in in-line mode benefits the detection of suspicious areas in mammography images by adding the edge enhancement effect to the reconstructed slices.

Minor changes in the macrocyclic ligands but major consequences on the efficiency of gold nanoparticles designed for radiosensitization.

Many studies have been devoted to adapting the design of gold nanoparticles to efficiently exploit their promising capability to enhance the effects of radiotherapy. In particular, the addition of magnetic resonance imaging modality constitutes an attractive strategy for enhancing the selectivity of radiotherapy since it allows the determination of the most suited delay between the injection of nanoparticles and irradiation. This requires the functionalization of the gold core by an organic shell composed of thiolated gadolinium chelates. The risk of nephrogenic systemic fibrosis induced by the release of gadolinium ions should encourage the use of macrocyclic chelators which form highly stable and inert complexes with gadolinium ions. In this context, three types of gold nanoparticles (Au@DTDOTA, Au@TADOTA and Au@TADOTAGA) combining MRI, nuclear imaging and radiosensitization have been developed with different macrocyclic ligands anchored onto the gold cores. Despite similarities in size and organic shell composition, the distribution of gadolinium chelate-coated gold nanoparticles (Au@TADOTA-Gd and Au@TADOTAGA-Gd) in the tumor zone is clearly different. As a result, the intravenous injection of Au@TADOTAGA-Gd prior to the irradiation of 9L gliosarcoma bearing rats leads to the highest increase in lifespan whereas the radiophysical effects of Au@TADOTAGA-Gd and Au@TADOTA-Gd are very similar.

New irradiation geometry for microbeam radiation therapy.

Microbeam radiation therapy (MRT) has the potential to treat infantile brain tumours when other kinds of radiotherapy would be excessively toxic to the developing normal brain. MRT uses extraordinarily high doses of x-rays but provides unusual resistance to radioneurotoxicity, presumably from the migration of endothelial cells from 'valleys' into 'peaks', i.e., into directly irradiated microslices of tissues. We present a novel irradiation geometry which results in a tolerable valley dose for the normal tissue and a decreased peak-to-valley dose ratio (PVDR) in the tumour area by applying an innovative cross-firing technique. We propose an MRT technique to orthogonally crossfire two arrays of parallel, nonintersecting, mutually interspersed microbeams that produces tumouricidal doses with small PVDRs where the arrays meet and tolerable radiation doses to normal tissues between the microbeams proximal and distal to the tumour in the paths of the arrays.

A software platform for phase contrast x-ray breast imaging research.

PURPOSE: To present and validate a computer-based simulation platform dedicated for phase contrast x-ray breast imaging research. METHODS: The software platform, developed at the Technical University of Varna on the basis of a previously validated x-ray imaging software simulator, comprises modules for object creation and for x-ray image formation. These modules were updated to take into account the refractive index for phase contrast imaging as well as implementation of the Fresnel-Kirchhoff diffraction theory of the propagating x-ray waves. Projection images are generated in an in-line acquisition geometry. To test and validate the platform, several phantoms differing in their complexity were constructed and imaged at 25 keV and 60 keV at the beamline ID17 of the European Synchrotron Radiation Facility. The software platform was used to design computational phantoms that mimic those used in the experimental study and to generate x-ray images in absorption and phase contrast modes. RESULTS: The visual and quantitative results of the validation process showed an overall good correlation between simulated and experimental images and show the potential of this platform for research in phase contrast x-ray imaging of the breast. The application of the platform is demonstrated in a feasibility study for phase contrast images of complex inhomogeneous and anthropomorphic breast phantoms, compared to x-ray images generated in absorption mode. CONCLUSIONS: The improved visibility of mammographic structures suggests further investigation and optimisation of phase contrast x-ray breast imaging, especially when abnormalities are present. The software platform can be exploited also for educational purposes.

The design and use of a dual-frequency surface coil providing proton images for improved localization in 31P spectroscopy of small lesions.

Nuclear magnetic resonance (NMR) spectroscopy of small lesions is restricted by the difficulties of localizing the surface coil with respect to the lesion and the problem of ensuring that signal is only obtained from the lesion and not from surrounding tissue. A double-tuned coil has been developed that permits NMR proton images to be obtained from a region of interest, prior to carrying out 31P spectroscopy of the same region with the same coil, without the need for further adjustment. The coil provides a means of accurately localizing the region from which the 31P signal is obtained, whilst offering a means of accurately applying 31P signal localization methods, and the possibility of making corrections for the nonuniform sensitivity of a given surface coil. The coil makes use of two parallel resonant circuits, with independent rf connections, but sharing a common coil. Simulated shorted and open circuit lambda /4 cables are used, respectively, to open circuit each circuit at the resonant frequency of the other circuit and ensure that the simulated lambda /4 line is short circuited for each circuit at the circuit's resonant frequency. At 63.6 MHz, the Q of the coil was 190 unloaded and 90 loaded, and at 25.7 MHz the Q was 210 unloaded and 140 loaded, for a 4-cm-diam coil. The coil has been used to obtain proton images and 31P spectra. A circuit employing only one input was also developed.

Degenerative cartilage lesions of the hip--magnetic resonance evaluation.

The capability of magnetic resonance imaging (MRI) to visualize early degenerative arthritis of the hip was investigated. The study was performed on 8 healthy students and 45 elderly volunteers. Images were obtained by using an electronically variable Helmholtz coil (switched-array coil, SAC). In order to diagnose degenerative lesions of the joint cartilage, FISP sequences with a flip angle of 70 degrees were found preferable to compared sequences. MRI-detectable signs of degenerative arthritis of the hip were narrowed joint space due to partially thinned cartilage layers, focal areas of either increased or decreased signal intensity in the hyaline cartilage, complete loss of cartilage, and signal variation in the bone marrow. MRI of the hip may be appropriate to detect early degenerative changes in the hips of young high-risk patients to facilitate therapy planning.

[Magnetic resonance tomography of the orbit using surface coils. Study technic, anatomy and initial clinical experience]. / Kernspintomographie der Orbita mit Oberflächenspulen. Untersuchungstechnik, Anatomie und erste klinische Erfahrungen.

MRI of the orbit is strongly improved by the use of surface coils due to a higher signal-to-noise ratio. Oblique views without moving the patient present the optic nerve in full length on one slice. First experience with a small number of cases demonstrates normal anatomy and lesions in detail only at T1-weighted pulse sequences. Losses in contrast variation and detail accuracy are caused by movements of the eyeballs. Edge artifacts due to chemical shifting impair the image quality. So far there are no pointers towards tissue-specific signal intensity behaviour. Procedure and most favourable parameters at 1 tesla are given.

[High-resolution nuclear spin tomography of the hip joint using a Helmholtz surface coil]. / Hochauflösende Kernspintomographie des Hüftgelenks unter Anwendung einer Helmholtz-Oberflächenspule.

A specially constructed Helmholtz surface coil enables one to obtain high resolution nuclear tomograms of the hip. Anatomical structures which are clinically important and which can regularly be shown are described. A pilot study has been carried out on 16 patients and typical findings are described in necrosis of the femoral head, osteoarthritis and changes resulting from tumours in the region. Possible further applications are discussed.

[MR tomographic demonstration of liquor pulsation]. / MR-tomographische Darstellung von Liquorpulsationen.

With ECG-gated FLASH-sequences motion of cerebrospinal fluid (CSF) is demonstrated in axial slices of the zervikal vertebral column. The course of the movement is dissolved by signal enhancement of flowing structures in magnitude images and by velocity-dependent phases. It is shown with both methods, that the oscillation of the CSF within the cardiac cycle is superimposed by a directed movement, with is cranial directed in the lateral cervical subarachnoidal spaces and caudal in the ventral subarachnoidal spaces.

[A simplified technic in high-resolution MR tomography of the shoulder: ZEPRA (Zoom of Eccentric Positioned Regions by active Aliasing)]. / Vereinfachte Technik bei der hochauflösenden MR-Tomographie der Schulter: ZEPRA.

A fairly easy method for high-resolution MR imaging of the shoulder is described. The combination of a defined arrangement of the gradients with a small-volume Helmholtz coil provides the possibility of a high zoom of structures apart from the magnet's centre. The maximal achievable zoom factor depends on the ratio of FOV/sensitive coil volume. The ZEPRA method acts by phase-encoded aliasing only. With this technique all interesting soft tissue of the shoulder may readily be visualized in every direction and with every type of sequence.

[Results of magnetic resonance tomography of the temporomandibular joint using optimized surface coils]. / Ergebnisse der Kernspintomographie des Temporomandibulargelenkes mittels optimierter Oberflächenspulen.

One hundred temporo-mandibular joints were examined with a super-conducting nuclear resonance tomograph (1.0 Tesla) using various high resolution surface coils. The optimal method proved to be a spin echo sequence with a repetition time of 1,000 msec and an echo period of 28 msec with a 4 mm slice width. There were significant advantages from the non-invasive MRT diagnosis of the temporo-mandibular joints when compared with CT and with arthrography in recognising abnormal discs, changes in the tissues and for post-operative control.

[Indications for the application of a high resolution coil in MR tomography]. / Indikationen zur Applikation einer Hochauflösungsspule in der MR-Tomographie.

This is the first study with high spatial resolution Magnetic Resonance Imaging (MRI), performed with a high resolution coil in a clinical whole-body system. Measurements were recorded with a slice thickness of 2 mm. A 256 x 256 matrix and a 2.5 cm field of view were used resulting in a pixel size of 0.01 mm2. MR images of the skin, hand, wrist, knee and ankle of 14 healthy volunteers, of three anatomic pathology tissue specimens and of three formalin-fixed specimens were obtained. Normal anatomy was identified and compared with the three gross anatomic pathology sections. The skin, hands, wrists and ankles of 30 patients were examined and a variety of pathological lesions were detected, including cutaneous neoplasms and ulceration, acute and chronic tendon lesions and pathologic features of the bone and wrist. Based on the excellent imaging of anatomic detail and superior contrast resolution, high resolution MRI proved an important complement for preoperative diagnosis.

[MRT of the eye: the normal anatomy and detection of the smallest lesions with a high-resolution surface coil]. / MRT des Auges: Normalanatomie und Nachweis kleinster Läsionen mit einer hochauflösenden Oberflächenspule.

PURPOSE: A new, high-resolution surface coil for MRI of the eye was evaluated with regard to practicability, image quality and sensitivity for small lesions. MATERIAL AND METHODS: 48 patients in whom a space-occupying lesion of the eye or orbit was suspected were examined (1.5 T tomograph, 5 cm surface coil, T1- and T2-weighted spin-echo sequences, the former before and after i.v. gadolinium DTPA). RESULTS: 45/48 patients tolerated MR with the high-resolution surface coil. No adverse effects were experienced by the patients. In 11/48 patients a space occupying lesion of the eye was detected (melanoma, 5; metastases, 2; haemorrhage, 1; malformation, hamartoma and scarring after melanoma, one each). The smallest detectable lesion had a thickness of < 1 mm. CONCLUSION: First experiences with the high-resolution surface coil indicate that this device is suited for detection of very small lesions of the eye.

Microorganisms and biomolecules in space environment experiment ES 029 on Spacelab-1.

Bacterial spores are proper test organisms for studying problems of space biology and exobiology. During the Spacelab 1 mission, studies on the limiting factors for survival of Bacillus subtilis spores in free space have been performed. An exposure tray on the pallet of Spacelab 1 accomodated 316 samples of dry spores for treatment with space vacuum and/or the following selected wavelengths of solar UV: > 170 nm, 220 nm, 240nm, 260nm and 280 nm. After recovery, inactivation, mutation induction, reparability, and photochemical damages in DNA and protein have been studied. The results contribute to the understanding of the mechanisms of increased UV sensitivity of bacterial spores in vacuo and to a better assessment of the chance of survival of resistant forms in space and of interplanetary transfer of life.