Color-coded summation images for the evaluation of blood flow in endovascular aortic dissection fenestration.

BACKGROUND: To analyze the benefit of color-coded summation images in the assessment of target lumen perfusion in patients with aortic dissection and malperfusion syndrome before and after fluoroscopy-guided aortic fenestration. METHODS: Between December 2011 and April 2020 25 patients with Stanford type A (n = 13) or type B dissection (n = 12) and malperfusion syndromes were treated with fluoroscopy-guided fenestration of the dissection flap using a re-entry catheter. The procedure was technically successful in 100% of the cases and included additional iliofemoral stent implantation in four patients. Intraprocedural systolic blood pressure measurements for gradient evaluation were performed in 19 cases. Post-processed color-coded DSA images were obtained from all DSA series before and following fenestration. Differences in time to peak (dTTP) values in the compromised aortic lumen and transluminal systolic blood pressure gradients were analyzed retrospectively. Correlation analysis between dTTP and changes in blood pressure gradients was performed. RESULTS: Mean TTP prior to dissection flap fenestration was 6.85 ± 1.35 s. After fenestration, mean TTP decreased significantly to 4.96 ± 0.94 s (p < 0.001). Available systolic blood pressure gradients between the true and the false lumen were reduced by a median of 4.0 mmHg following fenestration (p = 0.031), with significant reductions in Stanford type B dissections (p = 0.013) and minor reductions in type A dissections (p = 0.530). A moderate correlation with no statistical significance was found between dTTP and the difference in systolic blood pressure (r = 0.226; p = 0.351). CONCLUSIONS: Hemodynamic parameters obtained from color-coded DSA confirmed a significant reduction of TTP values in the aortic target lumen in terms of an improved perfusion in the compromised aortic region. Color-coded DSA might thus be a suitable complementary tool in the assessment of complex vascular patterns prevailing in aortic dissections, especially when blood pressure measurements are not conclusive or feasible.

Development of an anthropomorphic spine phantom suitable for fusion of MR neurography with interventional flat-panel CT.

PURPOSE: To design a spine phantom suitable for fusion of MR neurography (MRN) with interventional flat panel computed tomography (FPCT) images from tissue-equivalent agarose gels and artificial nerves in MRI, including material with equal attenuation to bone in computed tomography (CT). METHODS: T1-/T2-relaxation times of target tissue were determined in vivo (n = 5) using MR mapping-techniques. Serial dilution of castor oil lipogels was performed ex vivo in order to define correct composition for tissue-equivalent relaxation times. Similarly, serial dilution series of calcium carbonate (CaCO3) and barium sulphate (BaSO4) in synthetic resin were used to adjust radiodensity of selected vertebral bodies (L1-L5) and sacrum in CT. Nerve tissue was simulated with agarose-impregnated polyethylene fibers. Spine phantom was assembled using respective components in anthropomorphic geometry. A fat-saturated, T2-weighted 3D SPACE STIR sequence was acquired for MRN and subsequently fused with an on-site FPCT scan of the phantom. RESULTS: In vivo T1-/T2-values for fat tissue were found to be at 394 ± 16 ms and 161 ± 16 ms, corresponding to a castor oil concentration of 50%. Analogously, bone marrow-equivalent values were measured at 822 ± 21 ms and 67 ± 6 ms, simulated with 40% castor oil. Cortical bone-like radiodensity of 1'115 ± 80 HU was achieved for artificial bone with 30% CaCO3 and 1.5% BaSO4. Simulated nerves were successfully depicted in MRN and fused with FPCT, combining optimal contrasts for nerves and bones on-site. CONCLUSIONS: The customized phantom showed analogous tissue contrasts to in vivo conditions in both MRN and FPCT, facilitating simulations of fusion-image guided spine interventions.

C-arm flat-panel CT arthrography of the shoulder: Radiation dose considerations and preliminary data on diagnostic performance.

OBJECTIVES: To investigate radiation dose and diagnostic performance of C-arm flat-panel CT (FPCT) versus standard multi-detector CT (MDCT) shoulder arthrography using MRI-arthrography as reference standard. METHODS: Radiation dose of two different FPCT acquisitions (5 and 20 s) and standard MDCT of the shoulder were assessed using phantoms and thermoluminescence dosimetry. FPCT arthrographies were performed in 34 patients (mean age 44 ± 15 years). Different joint structures were quantitatively and qualitatively assessed by two independent radiologists. Inter-reader agreement and diagnostic performance were calculated. RESULTS: Effective radiation dose was markedly lower in FPCT 5 s (0.6 mSv) compared to MDCT (1.7 mSv) and FPCT 20 s (3.4 mSv). Contrast-to-noise ratios (CNRs) were significantly (p < 0.05) higher in FPCT 20-s versus 5-s protocols. Inter-reader agreements of qualitative ratings ranged between к = 0.47-1.0. Sensitivities for cartilage and rotator cuff pathologies were low for FPCT 5-s (40 % and 20 %) and moderate for FPCT 20-s protocols (75 % and 73 %). FPCT showed high sensitivity (81-86 % and 89-99 %) for bone and acromioclavicular-joint pathologies. CONCLUSION: Using a 5-s protocol FPCT shoulder arthrography provides lower radiation dose compared to MDCT but poor sensitivity for cartilage and rotator cuff pathologies. FPCT 20-s protocol is moderately sensitive for cartilage and rotator cuff tendon pathology with markedly higher radiation dose compared to MDCT. KEY POINTS: • FPCT shoulder arthrography is feasible with fluoroscopy and CT in one workflow. • A 5-s FPCT protocol applies a lower radiation dose than MDCT. • A 20-s FPCT protocol is moderately sensitive for cartilage and tendon pathology.

Systematic analysis of RBE and related quantities using a database of cell survival experiments with ion beam irradiation.

For tumor therapy with light ions and for experimental aspects in particle radiobiology the relative biological effectiveness (RBE) is an important quantity to describe the increased effectiveness of particle radiation. By establishing and analysing a database of ion and photon cell survival data, some remarkable properties of RBE-related quantities were observed. The database consists of 855 in vitro cell survival experiments after ion and photon irradiation. The experiments comprise curves obtained in different labs, using different ion species, different irradiation modalities, the whole range of accessible energies and linear energy transfers (LETs) and various cell types. Each survival curve has been parameterized using the linear-quadratic (LQ) model. The photon parameters, α and ß, appear to be slightly anti-correlated, which might point toward an underlying biological mechanism. The RBE values derived from the survival curves support the known dependence of RBE on LET, on particle species and dose. A positive correlation of RBE with the ratio α/ß of the photon LQ parameters is found at low doses, which unexpectedly changes to a negative correlation at high doses. Furthermore, we investigated the course of the ß coefficient of the LQ model with increasing LET, finding typically a slight initial increase and a final falloff to zero. The observed fluctuations in RBE values of comparable experiments resemble overall RBE uncertainties, which is of relevance for treatment planning. The database can also be used for extensive testing of RBE models. We thus compare simulations with the local effect model to achieve this goal.

Calculation of the biological effects of ion beams based on the microscopic spatial damage distribution pattern.

PURPOSE: To present details of the recent version of the 'Local Effect Model' (LEM), that has been developed and implemented in treatment planning for the ion beam therapy pilot project performed at GSI Helmholtzzentrum für Schwerionenforschung in Darmstadt, Germany. MATERIALS AND METHODS: The new version of the model is based on a detailed consideration of the spatial distribution of the initial damages, i.e., double-strand breaks (DSB). This spatial distribution of DSB is obtained from the radial dose profile of the ion track using Monte Carlo methods. These distributions are then analyzed with regard to the proximity of DSB. This version of the model also facilitates the calculation of full dose response curves up to arbitrary high doses, thus allowing to thoroughly check the approximations previously used to estimate the quadratic term (ß-term) for the linear-quadratic description of dose response curves. RESULTS: The accuracy of the model predictions is demonstrated by good agreement of the relative biological effectiveness (RBE) as a function of the linear energy transfer (LET) with experimental data obtained for V79 cells after carbon irradiation. The ß-values predicted by the full simulation tend to be larger as compared to the approximation in the intermediate LET range. CONCLUSION: The new version of the model allows a more mechanistic description of the biological effects of ion radiation. The full simulation is a prerequisite for tests of the validity of the approach at high doses, which are of particular interest for application in hypofractionation studies.

Quantification of the relative biological effectiveness for ion beam radiotherapy: direct experimental comparison of proton and carbon ion beams and a novel approach for treatment planning.

PURPOSE: To present the first direct experimental in vitro comparison of the biological effectiveness of range-equivalent protons and carbon ion beams for Chinese hamster ovary cells exposed in a three-dimensional phantom using a pencil beam scanning technique and to compare the experimental data with a novel biophysical model. METHODS AND MATERIALS: Cell survival was measured in the phantom after irradiation with two opposing fields, thus mimicking the typical patient treatment scenario. The novel biophysical model represents a substantial extension of the local effect model, previously used for treatment planning in carbon ion therapy for more than 400 patients, and potentially can be used to predict effectiveness of all ion species relevant for radiotherapy. A key feature of the new approach is the more sophisticated consideration of spatially correlated damage induced by ion irradiation. RESULTS: The experimental data obtained for Chinese hamster ovary cells clearly demonstrate that higher cell killing is achieved in the target region with carbon ions as compared with protons when the effects in the entrance channel are comparable. The model predictions demonstrate agreement with these experimental data and with data obtained with helium ions under similar conditions. Good agreement is also achieved with relative biological effectiveness values reported in the literature for other cell lines for monoenergetic proton, helium, and carbon ions. CONCLUSION: Both the experimental data and the new modeling approach are supportive of the advantages of carbon ions as compared with protons for treatment-like field configurations. Because the model predicts the effectiveness for several ion species with similar accuracy, it represents a powerful tool for further optimization and utilization of the potential of ion beams in tumor therapy.

Response of human hematopoietic stem and progenitor cells to energetic carbon ions.

PURPOSE: To characterise the radiation response of human hematopoietic stem and progenitor cells (HSPC) with respect to X and carbon ion irradiation. MATERIALS AND METHODS: HSPC from peripheral blood of healthy donors treated with granulocyte-colony stimulating factor (G-CSF) were enriched for the transmembrane glycoprotein CD34 (cluster of differentiation) and irradiated with X rays or carbon ions (29 keV/microm monoenergetic beam and 60-85 keV/microm spread-out Bragg peak), mimicking radiotherapy conditions. Apoptotic cell death, cell cycle progression and the frequency of chromosomal aberrations were determined. RESULTS: After radiation exposure no inhibition in the progression of the cell cycle was detected. However, an enhanced frequency of apoptotic cells and an increase in aberrant cells were observed, both effects being more pronounced for carbon ions than X rays, resulting in a relative biological effectiveness (RBE) of 1.4-1.7. The fraction of complex-type aberrations was higher following carbon ion exposure. CONCLUSIONS: RBE values of carbon ions are low, as expected for radiosensitive cells. The observed frequencies of apoptotic cells and chromosome aberrations in HSPC are similar to those reported for human peripheral blood lymphocytes suggesting that at least with respect to apoptosis and chromosomal aberrations mature lymphocytes reflect the respective radiation responses of their proliferating progenitors.

Comparison of biological effectiveness of carbon-ion beams in Japan and Germany.

PURPOSE: To compare the biological effectiveness of 290 MeV/amu carbon-ion beams in Chiba, Japan and in Darmstadt, Germany, given that different methods for beam delivery are used for each. METHODS AND MATERIALS: Murine small intestine and human salivary gland tumor (HSG) cells exponentially growing in vitro were irradiated with 6-cm width of spread-out Bragg peaks (SOBPs) adjusted to achieve nearly identical beam depth-dose profiles at the Heavy-Ion Medical Accelerator in Chiba, and the SchwerIonen Synchrotron in Darmstadt. Cell kill efficiencies of carbon ions were measured by colony formation for HSG cells and jejunum crypts survival in mice. Cobalt-60 gamma rays were used as the reference radiation. Isoeffective doses at given survivals were used for relative biological effectiveness (RBE) calculations and interinstitutional comparisons. RESULTS: Isoeffective D(10) doses (mean +/- standard deviation) of HSG cells ranged from 2.37 +/- 0.14 Gy to 3.47 +/- 0.19 Gy for Chiba and from 2.31 +/- 0.11 Gy to 3.66 +/- 0.17 Gy for Darmstadt. Isoeffective D(10) doses of gut crypts after single doses ranged from 8.25 +/- 0.17 Gy to 10.32 +/- 0.14 Gy for Chiba and from 8.27 +/- 0.10 Gy to 10.27 +/- 0.27 Gy for Darmstadt, whereas isoeffective D(30) doses after three fractionated doses were 9.89 +/- 0.17 Gy through 13.70 +/- 0.54 Gy and 10.14 +/- 0.20 Gy through 13.30 +/- 0.41 Gy for Chiba and Darmstadt, respectively. Overall difference of RBE between the two facilities was 0-5% or 3-7% for gut crypt survival or HSG cell kill, respectively. CONCLUSION: The carbon-ion beams at the National Institute of Radiological Sciences in Chiba, Japan and the Gesellschaft für Schwerionenforschung in Darmstadt, Germany are biologically identical after single and daily fractionated irradiation.

Radiobiological evaluation and correlation with the local effect model (LEM) of carbon ion radiation therapy and temozolomide in glioblastoma cell lines.

PURPOSE: To investigate the cytotoxic effect of high linear-energy transfer (LET) carbon irradiation on glioblastoma cells lines in combination with temozolomide (TMZ). METHODS AND MATERIALS: The cell lines U87-MG expressing wild-type p53 and LN229 expressing both mutant and wild-type p53 were irradiated with monoenergetic carbon ion beams (LET 172 keV/microm) or an extended Bragg peak (LET 103 keV/microm) after treatment with 10 microM or 20 microM TMZ. Cytotoxicity was measured by a clonogenic survival assay, and cell growth as well as cell cycle progression, were examined. RESULTS: The p53 mutant was more sensitive to X-ray irradiation than the p53 wild type cell line, which was also expressed in a shorter G2 block. High LET carbon ions show an increased biological effectiveness in both cell lines, which is consistent with the predictive calculations by the Local Effect Model (LEM) introduced by Scholz et al. The cell line LN229 was more sensitive to TMZ treatment than the U87MG cell line expressing wild-type p53 only. The combination of TMZ and irradiation showed an additive effect in both cell lines. CONCLUSION: High LET carbon ion irradiation is significantly more effective for glioblastoma cell lines compared to photon irradiation. An additional treatment with TMZ may offer a great chance especially for several tumor types.

Biophysical modeling of fragment length distributions of DNA plasmids after X and heavy-ion irradiation analyzed by atomic force microscopy.

The investigation of fragment length distributions of plasmid DNA gives insight into the influence of localized energy distribution on the induction of DNA damage, particularly the clustering of double-strand breaks. We present an approach that determines the fragment length distributions of plasmid DNA after heavy-ion irradiation by using the Local Effect Model. We find a good agreement of our simulations with experimental fragment distributions derived from atomic force microscopy (AFM) studies by including experimental constraints typical for AFM. Our calculations reveal that by comparing the fragmentation in terms of fluence, we can uniquely distinguish the effect of different radiation qualities. For very high-LET irradiation using nickel or uranium ions, no difference between their fragment distributions can be expected for the same dose level. However, for carbon ions with an intermediate LET, the fragmentation pattern differs from the distribution for very high-LET particles. The results of the model calculations can be used to determine the optimal experimental parameters for a demonstration of the influence of track structure on primary radiation damage. Additionally, we compare the results of our model for two different plasmid geometries.

Accuracy of the local effect model for the prediction of biologic effects of carbon ion beams in vitro and in vivo.

PURPOSE: To analyze the accuracy of relative biologic effectiveness (RBE) values for treatment planning in carbon ion radiotherapy based on the local effect model (LEM) and to discuss the implications on the clinically relevant depth dose profiles. METHODS AND MATERIALS: Predictions of the LEM are compared with a broad panel of experimental data in vitro and to the tolerance of the rat spinal cord in vivo. To improve the accuracy of the LEM, the description of track structure is modified by taking into account a velocity-dependent extension of the inner part of the track. RESULTS: The original version of the LEM (LEM I) underestimates the therapeutic ratio of carbon ions (i.e., the ratio of RBE in the Bragg peak region as compared with the RBE in the entrance channel). Although significantly reduced, the cluster extension of the LEM (LEM II) still shows the same tendency. Implementation of the modified track structure (LEM III) almost completely compensates these systematic deviations, and predictions of RBE by LEM III for high and low energetic carbon ions show good agreement for a wide panel of different cell lines, as well as for the tolerance of the rat spinal cord. As a consequence, the expected RBE in the normal tissue surrounding the tumor becomes significantly lower than estimated with the LEM in its original version (LEM I). CONCLUSIONS: The modified track structure description represents an empiric approach to improve the accuracy of the LEM for treatment planning. This will be particularly useful for further optimization of carbon ion therapy in general and with respect to comparison with other treatment modalities, such as protons or intensity-modulated radiotherapy.

Biophysical calculation of cell survival probabilities using amorphous track structure models for heavy-ion irradiation.

Both the microdosimetric kinetic model (MKM) and the local effect model (LEM) can be used to calculate the surviving fraction of cells irradiated by high-energy ion beams. In this study, amorphous track structure models instead of the stochastic energy deposition are used for the MKM calculation, and it is found that the MKM calculation is useful for predicting the survival curves of the mammalian cells in vitro for (3)He-, (12)C- and (20)Ne-ion beams. The survival curves are also calculated by two different implementations of the LEM, which inherently used an amorphous track structure model. The results calculated in this manner show good agreement with the experimental results especially for the modified LEM. These results are compared to those calculated by the MKM. Comparison of the two models reveals that both models require three basic constituents: target geometry, photon survival curve and track structure, although the implementation of each model is significantly different. In the context of the amorphous track structure model, the difference between the MKM and LEM is primarily the result of different approaches calculating the biological effects of the extremely high local dose in the center of the ion track.

Cluster effects within the local effect model.

The local effect model predicts the relative biological effectiveness (RBE) for different ions and cell lines starting from the corresponding experimental photon data and an amorphous track structure model. Here we present an extension of the model that takes cluster effects of single-strand breaks (SSBs) at the nanometer scale into account. In line with the main idea of the local effect model, we take the yields of SSBs and double-strand breaks (DSBs) from experimental photon data and use a Monte Carlo method to distribute them onto the DNA. We score clusters of SSBs where individual SSBs are separated by less than 25 bp as additional DSBs. Assuming that the number of DSBs is a measure of cell lethality, we derive a modified cell survival curve for photons that takes these cluster effects into account. In combination with an improved radial dose distribution, we find that the extended local effect model including cluster effects reproduces most experimental data better than the original local effect model and thus enhances the accuracy of the local effect model.