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Biomedical subjects

G Kraft

Publications and source records attributed to G Kraft.

At least 19 recordsLinked to original sources
PubMed2003

A track structure model for simulation of strand breaks in plasmid DNA after heavy ion irradiation.

We present a track structure model based on the local dose deposited around heavy ion tracks to explain the cross sections for single-strand and double-strand break induction in plasmid DNA in different aqueous buffers. The model is based only on measurable quantities, namely the effect distribution for inducing strand breaks after x-ray irradiation as a function of dose, and the radial dose distribution of the heavy ion track. The effect of indirect DNA damage mediated by free radicals produced in the water surrounding the DNA is accounted for by allowing the radial dose distribution to be smeared in space by an effective target size corresponding to the squared sum of the geometrical extension of the plasmid molecule and the mean free drift path of the radicals in the buffer solution. Our calculations reproduce well the measured cross sections for single-strand and double-strand break induction in SV40 plasmid DNA in various buffer solutions both as a function of the LET and of the specific energy of the heavy ion.

Buffers↗
PubMed2003

Three-dimensional dose verification with x-ray films in conformal carbon ion therapy.

A three-dimensional dose verification with photographic emulsions (x-ray films) was realized within the tumour therapy project at GSI Darmstadt, using carbon ions. We present Bragg-peak measurements for 88, 100 and 200 MeV/u carbon ion beams as the simplest case of dose verification. An actual patient treatment plan, composed by the superposition of Bragg-peaks having different energies and intensities, was used to perform a three-dimensional dose verification of an irregularly formed target volume. The shape of the measured dose distribution from film closely matches the intended irradiation volume. Furthermore, the calculated and measured optical density distribution is in good agreement with a maximum deviation of less than 10%.

Carbon Radioisotopes↗
PubMed2002

Calculation of the x-ray film response to heavy charged particle irradiation.

A model was developed to calculate the response of films to heavy ion irradiation as a function of particle type and energy. It is based on the local effect model and was extended to be applied to the non-homogeneous target of photographic emulsions. The calculation was performed for protons and carbon ions in the energy range from 2 to 430 MeV u(-1). The calculated film responses are in very good agreement with experimental data. Based on this model calculation a data base of film responses was set up. This enables a three-dimensional dose verification with films in the heavy ion tumour therapy project at GSI, Darmstadt.

Carbon↗
PubMed2002

MR nerve imaging in a prospective cohort of patients with suspected carpal tunnel syndrome.

OBJECTIVES: To evaluate the reliability and diagnostic accuracy of high-resolution MRI of the median nerve in a prospectively assembled cohort of subjects with clinically suspected carpal tunnel syndrome (CTS). METHODS: The authors prospectively identified 120 subjects with clinically suspected CTS from five Seattle-area clinics. All subjects completed a hand-pain diagram and underwent a standardized nerve conduction study (NCS). The reference standard for determining CTS status was a classic or probable hand pain diagram and NCS with a difference >0.3 ms between the 8-cm median and ulnar peak latencies. Readers graded multiple imaging parameters of the MRI on four-point scales. The authors also performed quantitative measurements of both the median nerve and carpal tunnel cross-sectional areas. NCS and MRI were interpreted without knowledge of the other study or the hand pain diagram. RESULTS: Intrareader reliability was substantial to near perfect (kappa = 0.76 to 0.88). Interreader agreement was lower but still substantial (kappa = 0.60 to 0.67). Sensitivity of MRI was greatest for the overall impression of the images (96%) followed by increased median nerve signal (91%); however, specificities were low (33 to 38%). The length of abnormal signal on T2-weighted images was significantly correlated with nerve conduction latency, and median nerve area was larger at the distal radioulnar joint (15.8 vs 11.8 mm(2)) in patients with CTS. A logistic regression model combining these two MR variables had a receiver operating characteristic area under the curve of 0.85. CONCLUSIONS: The reliability of MRI is high but the diagnostic accuracy is only moderate compared with a research-definition reference standard.

Adult↗
PubMed2001

Changes of fibrosis-related parameters after high- and low-LET irradiation of fibroblasts.

PURPOSE: To investigate the radiation-induced, premature terminal differentiation and collagen production of fibroblasts after heavy ion irradiation. These endpoints are discussed as an underlying cellular mechanism of fibrosis. MATERIALS AND METHODS: Normal human foreskin fibroblasts (AG1522B) were used to determine clonogenic survival, the premature differentiation and synthesis of extracellular matrix (ECM) proteins, e.g. collagen after irradiation with X-rays, 195 and 11.0 MeV u(-1) carbon ions and 9.9 MeV u(-1) nickel ions. Additionally, biopsies from the skin of minipigs were taken. Similar experiments were carried out after irradiation with X-rays and 195 MeV u(-1) carbon ions. RESULTS AND CONCLUSIONS: RBE for clonogenic survival as well as for fibrosis-related parameters for high-energy carbon ions are slightly above unity. Low-energy carbon ions with a higher LET are more efficient than X-rays, whereas the RBE of nickel ions is below unity. The results obtained for the differentiation pattern and protein production of porcine fibroblasts after irradiation with X-rays and high-energy carbon ions are in agreement with those obtained with human fibroblasts. An accumulation of fibrocytes with a concomitant increase in ECM protein production could be seen after in vitro irradiation. There is no indication of a higher RBE for fibrosis-related parameters compared with other endpoints (survival, chromosomal and DNA damage). The dose- and LET-dependence suggest that premature differentiation is a survival strategy after radiation damage.

Animals↗
PubMed2001

Analysis of Ar-ion and X-ray-induced chromatin breakage and repair in V79 plateau-phase cells by the premature chromosome condensation technique.

PURPOSE: The premature chromosome condensation technique has been used to compare chromatin breakage and repair in noncycling V79 cells following high and low LET radiation. MATERIALS AND METHODS: Plateau-phase V79 cells were exposed to graded doses of low energy Ar ions (LET 1233 keV/microm) and X-rays. Cells were fused to mitotic V79 cells immediately after exposure to examine initial chromatin breakage or after various time intervals of post-irradiation incubation to investigate the kinetics of chromatin break rejoining as well as the fraction of unrejoined fragments. RESULTS AND CONCLUSIONS: For both radiation qualities an average initial number of about 2.4 excess PCC fragments per cell per Gy was found increasing linearly with dose. The distributions of PCC chromosomes plus excess fragments among cells followed Poisson statistics after X-ray irradiation, while an overdispersion of the frequencies was observed after Ar-irradiation indicating that a single particle traversal through a cell nucleus can produce multiple chromatin lesions. Moreover, for both radiation types the rejoining of excess fragments has been examined. Both data sets could be fitted well to first-order kinetics with a single component. Despite similar rates of rejoining cellular repair was noticeably less effective for Ar ions than for X-rays. While after 10 h of post-irradiation incubation 60% of Ar ion induced excess fragments remained unrejoined, only 14% of X-ray-induced lesions were not rejoined. Furthermore, comparison of the residual number of excess PCC fragments with recently published data on the yield of chromosome aberrations in first post-irradiation metaphases shows that for both radiation types more aberrations are detected in interphase than in metaphase cells. Yet, for comparable doses this difference is more pronounced for Ar ions indicating that scoring of high LET induced aberrations in metaphase cells might result in a significant underestimation of the produced damage.

Animals↗
PubMed2001

Experimental investigations of the response of films to heavy-ion irradiation.

The response of films to heavy-ion irradiation was investigated systematically by recording dose-response curves for protons and carbon ions in an energy range of 8-430 MeV u(-1). In order to allow for an objective comparison of different experimental results, a practicable method was developed to decouple the value of the net optical density from the film's processing conditions and a precise definition of the film response was deduced. A qualitative explanation of the strong variation of the film response depending on particle type and energy is given, based on the particle's track structure. The data presented here form the basis for using films for dosimetry in mixed particle radiation fields and their application in the heavy-ion therapy project at GSI, Darmstadt.

Carbon↗
PubMed2001

What we can learn from heavy ion therapy for radioprotection in space.

A major problem in manned space flight is the impact of cosmic radiation, especially that of heavy charged particles since they have an elevated biological efficiency (RBE). The RBE estimation determines the potential exposure for man. It is one of the limiting factors for space flight and should be known very precisely. The same is true for heavy-ion tumor therapy where beams of carbon ions are used to treat deep-seated tumors. There, RBE values determine the dose distribution and are estimated using the Local Effect Model (LEM). The clinical results confirm the correctness of LEM and suggest to use the same theoretical approach to assess the impact of cosmic rays.

Carbon↗
PubMed2001

Mathematical models of radiation-induced mitotic delay: time course analysis and statistics of lesions.

Detailed investigations of high and low LET radiation induced chromosome aberrations in various mammalian cell lines have shown that the registered yield of aberrations depends on cell cycle progression delays. The effect of radiation on the cell kinetics can be analyzed in terms of kinetic growth models. The method yields the number of aberrant cells and the number of aberrations as totals obtained after integration over given time-interval.

Animals↗
PubMed2001

High-LET-induced chromosomal damage: time-dependent expression.

Chromosome aberrations are routinely analysed in metaphase cells at one sampling time post-irradiation. Yet, accumulating evidence shows that radiation-induced cycle perturbations and mitotic delay influence the yield of aberrations detectable in mitosis. In extended time-course studies a drastic increase in the number of aberrations with sampling time has been observed after particle irradiation, while after the exposure to sparsely ionizing radiation a less pronounced effect has been found. This difference in the time-course of chromosomal damage is particularly important for the determination of accurate RBE values. As will be discussed, meaningful RBE values for particles can only be obtained, if cells are analysed at multiple sampling times and the complete time-course of aberrations is considered. Otherwise, particle-induced damage will be over- or underestimated. Moreover, depending on the cell system chosen for the analysis, factors like the loss of damaged cells due to apoptosis or a permanent cell cycle arrest complicate the determination of accurate RBE values based on chromosome data.

Animals↗
PubMed2001

Heavy ion production of single- and double-strand breaks in plasmid DNA in aqueous solution.

Preliminary measurements on the production of single- and double-strand breaks in SV40 and phi X174 plasmid DNA by various heavy ions in radioprotective Tris buffer are presented. The dependence of the recorded yields on the LET of the incoming ions is discussed and shown to be comprehensible within the framework of a model based on the X-ray sensitivity of the exposed DNA and the local dose distribution inside the heavy ion track. The question of the influence of the chemical environment is addressed by comparing the measured cross sections to data recorded previously in more radiosensitive TE buffer. The results indicate that also for systems with high scavenging capacity RBE values larger than unity can be achieved with maximum values in the LET range 100-1000 keV micrometers-1.

Bacteriophage phi X 174↗
PubMed2000

[Carbon ion irradiation of skull base tumors at GSI. First clinical results and future perspectives].

BACKGROUND: Radiobiological and physical examinations suggest clinical advantages of heavy ion irradiation. We report the results of 23 women and 22 men (median age 48 years) with skull base tumors irradiated with carbon ion beams at the Gesellschaft für Schwerionenforschung (GSI), Darmstadt, from December 1997 until September 1999. PATIENTS AND METHODS: The study included patients with chordomas (17), chondrosarcomas (10) and other skull base tumors (Table 1). It is the first time that the intensity-controlled rasterscan-technique and the application of positron-emission tomography (PET) for quality assurance was used. All patients had computed tomography for three-dimensional-treatment planning (Figure 1). Patients with chordomas and chondrosarcomas underwent fractionated carbon ion irradiation in 20 consecutive days (median total dose 60 GyE). Other histologies were treated with a carbon ion boost of 15 to 18 GyE delivered to the macroscopic tumor after fractionated stereotactic radiotherapy (median total dose 63 GyE). RESULTS: Mean follow-up was 9 months. Irradiation was well tolerated by all patients. Partial tumor remission was seen in 7 patients (15.5%) (Figure 2). One-year local control rate was 94%. One patient (2.2%) deceased. No severe toxicity and no local recurrence within the treated volume were observed. CONCLUSION: Clinical effectiveness and technical feasibility of this therapy modality could clearly be demonstrated in our study. To evaluate the clinical relevance of the different beam modalities studies with larger patient numbers are necessary. To continue our project a new heavy ion accelerator exclusively for clinical use is planned to be constructed in Heidelberg.

Adolescent↗
PubMed2000

High-LET-induced chromosome aberrations in V79 cells analysed in first and second post-irradiation metaphases.

PURPOSE: As an extension of previous studies, the time-course of high-LET-induced chromosomal damage was investigated in first- and second-cycle V79 Chinese hamster cells. MATERIALS AND METHODS: Cells were exposed in G1 to 10.4 MeV/u Ar ions (LET = 1226 keV/microm) and chromosomal damage was measured at 2h sampling intervals between 10 h and 34 h after irradiation. To distinguish between cells in different post-irradiation cycles, the fluorescence-plus-Giemsa technique was applied. RESULTS: For first- and second-generation cells, the number of aberrant metaphases and aberrations per metaphase were found to increase markedly with sampling time, demonstrating that cell cycle progression was delayed according to the number of lesions carried by the cell. To account for the time-dependent expression of chromosomal damage a mathematical approach was used based on the integrated flux of aberrant cells entering mitosis. Moreover, the analysis of Ar ion-induced chromosome lesions confirmed that high-LET radiation results in specific changes in the spectrum of aberration types. In particular, an increased rate of chromatid-type aberrations as well as a high frequency of chromosomal breaks was found, although the cells were exposed in G1. CONCLUSIONS: Due to the fact that cells collected at one sampling time are not representative of the entire population, the complete time-course of chromosomal damage has to be taken into account for the determination of a meaningful RBE value. Otherwise, the analysis of chromosomal damage can result in a pronounced over- or underestimation of the RBE depending on the subpopulation of cells entering mitosis at that particular sampling time.

Animals↗
PubMed2000

Treatment planning for heavy-ion radiotherapy: physical beam model and dose optimization.

We describe a novel code system, TRiP, dedicated to the planning of radiotherapy with energetic ions, in particular 12C. The software is designed to cooperate with three-dimensional active dose shaping devices like the GSI raster scan system. This unique beam delivery system allows us to select any combination from a list of 253 individual beam energies, 7 different beam spot sizes and 15 intensity levels. The software includes a beam model adapted to and verified for carbon ions. Inverse planning techniques are implemented in order to obtain a uniform target dose distribution from clinical input data, i.e. CT images and patient contours. This implies the automatic generation of intensity modulated fields of heavy ions with as many as 40000 raster points, where each point corresponds to a specific beam position, energy and particle fluence. This set of data is directly passed to the beam delivery and control system. The treatment planning code has been in clinical use since the start of the GSI pilot project in December 1997. Forty-eight patients have been successfully planned and treated.

Algorithms↗
PubMed2000

Depth scanning for a conformal ion beam treatment of deep seated tumours.

Only target-conformal treatment allows one to exploit the advantages of ion beams (the increased dose and high biological efficiency at the end of the particle range) to a maximum extent. Up to now, target-conformal treatments such as spot scanning or intensity-controlled raster scanning have used fast magnetic lateral deflection in one or two directions perpendicular to the beam axis and a slow range variation in the longitudinal axis by active or passive energy variation. The present paper describes a new method for conformal irradiation with a fast intensity-controlled longitudinal scan in the beam direction, called 'depth scanning'. Its advantages and disadvantages will be discussed. First experimental results from depth scanning will be presented.

Dose-Response Relationship, Radiation↗
PubMed2000

Three-dimensional BANG gel dosimetry in conformal carbon ion radiotherapy.

In this study we applied BANG polymer-gel dosimetry using magnetic resonance imaging (MRI) to densely ionizing radiation such as carbon ion beams. BANG polymer gels were irradiated with a quadratic field of monoenergetic 12C ions at different beam energies in the range of 135 MeV u(-1) to 410 MeV u(-1). They were irradiated at the radiotherapy facility of the GSI, Darmstadt, Germany. Our object was to examine the saturation effect for densely ionizing radiation that occurs at high values of linear energy transfer (LET). The examination yielded the first effectiveness values that will be discussed in the following sections. A solid sphere and a hollow sphere were both irradiated with a horizontal pencil beam from the raster scanning facility at energies of 268 MeV u(-1) (solid sphere) and 304 MeV u(-1) (hollow sphere) respectively. MR dosimetry measurements were compared with data from a planning system. As far as quality is concerned, there is good agreement between the measured dose distributions of both samples and the dose maps from the planning software. The measured MR signals cannot be converted into absolute dose, since the relative efficiency is still unknown for mixed radiation fields of primary carbon ions and it is known only to a limited extent for nuclear fragments with different energies from highly energetic photon radiation. Model calculations are in progress in order to facilitate conversions of measured MR signals into dose.

Acrylamides↗
PubMed1999

Peripheral neuropathy caused by proteolipid protein gene mutations.

Pelizaeus-Merzbacher disease (PMD) is a dysmyelinating disorder of the central nervous system typically caused by duplications or missense mutations of the proteolipid protein (PLP) gene. Most investigators have found that peripheral nerve function and structure is normal in PMD patients. We have found that null mutations of the PLP gene cause demyelinating peripheral neuropathy, whereas duplications and a proline 14 to leucine mutation do not affect nerve function. A family with a nonsense mutation at position 144, which affects only PLP but not the alternatively spliced gene product DM20, has a very mild syndrome, including normal peripheral nerve function. Our findings suggest that DM20 alone is sufficient to maintain normal nerve function and that there may be domains of PLP/DM20 that have a relatively more active role in the peripheral nervous system compared with that in the central nervous system.

Amino Acid Sequence↗