Biomedical subjects

Markus Alber

Publications and source records attributed to Markus Alber.

18 recordsLinked to original sources

PubMed2007

Influence of dose engine accuracy on the optimum dose distribution in intensity-modulated proton therapy treatment plans.

Analytical dose computation algorithms like pencil beam algorithms (PB) are presently used for clinical treatment planning in intensity-modulated proton therapy. PB offer fast computation times, but are based on substantial approximations. Monte Carlo algorithms (MC) offer better accuracy, but are slower. We present a comparison of optimized treatment plans for six patients computed either with PB or MC. Both PB and MC are used during optimization, plus MC is used to recompute PB results. PB is used with different accuracy settings that define the coarseness of approximation. We evaluate the errors of PB optimized treatment plans via comparison with MC optimized plans (convergence errors) and MC recomputed plans (systematic errors) occurring for different accuracy settings of the PB. The level of lateral heterogeneities, being one of the main sources of inaccuracies of the PB, is quantified by a formula. In geometries with high levels of lateral heterogeneities, the shortcomings of PB are most obvious. For these geometries, simple PB lead to clinically significant differences and more accurate PB settings have to be used to diminish the error. The most accurate PB settings lead however to longer computing times by approximately a factor of 2 to 4 compared to PB with simple settings. Although the errors can be diminished, they cannot be fully eliminated even with sophisticated PB. Further gain in accuracy can therefore only be reached with MC in optimization. The use of MC in optimization is technically feasible, the computing times are however about 25 to 50 times longer compared to PB with most accurate settings.

Algorithms↗

PubMed2006

Imaging oxygenation of human tumours.

Tumour hypoxia represents a significant challenge to the curability of human tumours leading to treatment resistance and enhanced tumour progression. Tumour hypoxia can be detected by non-invasive and invasive techniques but the inter-relationships between these remains largely undefined. (18)F-MISO and Cu-ATSM-PET, and BOLD-MRI are the lead contenders for human application based on their non-invasive nature, ease of use and robustness, measurement of hypoxia status, validity, ability to demonstrate heterogeneity and general availability, these techniques are the primary focus of this review. We discuss where developments are required for hypoxia imaging to become clinically useful and explore potential new uses for hypoxia imaging techniques including biological conformal radiotherapy.

Cell Hypoxia↗

PubMed2006

Combined uptake of [18F]FDG and [18F]FMISO correlates with radiation therapy outcome in head-and-neck cancer patients.

PURPOSE: FDG PET is frequently used for radiotherapy (RT) planning to determine the tumour extent. Similarly, FMISO is used to assess the hypoxic sub-volume. The relationship between the volumes determined on the basis of FDG and FMISO was investigated. Additionally, the quantitative correlation of the tracers on a voxel basis was studied. METHODS: Twelve head-and-neck cancer (HNC) patients underwent FDG and FMISO PET examinations prior to RT treatment. The tumour volumes assessed by the two tracers and also the voxel-based joint uptake values were investigated. The characteristic shapes and patterns of the determined scatter plots were analyzed. A number of different variables such as the maximum uptake values of FDG and FMISO, the FDG and FMISO positive volumes, the slope m of the regression line and the scatter width sigma of the scatter plots were tested for their ability to stratify the patient group with respect to treatment outcome. RESULTS: A diversity of characteristic FDG-FMISO distributions was observed in the patient group. However, no general correlation of enhanced glucose metabolism and FMISO uptake was observed. The maximum uptake of FMISO (p=0.045) showed borderline significance for stratifying the patient group. FDG positive tumour volume, hypoxic fraction, maximum FDG uptake and m were not significant. Sigma turned out to be the most significant variable (p=0.008) to predict treatment success probabilities. CONCLUSION: FMISO and FDG PET data provide independent information about the examined tumour. A quantification of the correlated tracer uptake seems to be meaningful.

Aged↗

PubMed2006

[Dosimetric consequences of the application of a rectum hull-planning volume for treatment planning of intensity modulated radiotherapy of prostate cancer].

The present study evaluated a hull-volume definition strategy for the planning organ at risk volume (PRV) for the rectum in the planning of radiotherapy of prostate cancer. The bounding volumes of rectum contours of 1 to 5 CT scans were compared on the basis of the rectum coverage probabilities for 5 patients. In addition, IMRT treatment plans were optimized using the rectum hull PRV5 of 5 CTs and each of the conventional rectum contours PRV1. The plans were compared on the basis of the organ doses caused by the individual organ motion. PRV5 allowed to cover the rectum with a probability of nearly 90% (PRV1 67%). Rectal wall dose showed a great variability for PRV1, while planned and treatment dose agreed well for PRV5 due to the improved geometric information which resulted in a better rectal sparing. In conclusion, the rectum hull-volume PRV5 is a well suited PRV for planning of IMRT dose distributions allowing dose escalation as well as rectal sparing.

Humans↗

PubMed2006

The influence of noise in full Monte Carlo ML-EM and dual matrix reconstructions in positron emission tomography.

Monte Carlo (MC) simulations in positron emission tomography (PET) play an important role in detector modeling and algorithm testing. Whereas the simulations are widely used in a forward projection manner to accomplish this task, ideally they should be included into the reconstruction process itself. It is therefore desirable to investigate the convergence properties and the propagation of MC noise of these kinds of reconstruction algorithms. MC simulations were integrated into the maximum likelihood expectation maximization (ML-EM) algorithm in two different ways. In the full matrix approach the system matrix was calculated by running MC simulations, including scatter. This matrix was used in both the projector and the backprojector. In the dual matrix (DM) approach, MC simulations were used to incorporate scatter in the projector, whereas the backprojector only comprised attenuation. Repeated reconstructions with different MC seeds allowed a statistical analysis of the error at each iteration step and made it possible to investigate separately the propagation of the MC noise that was introduced by the sinogram, by the projector, and by the matrix. Both approaches resulted in similar images, but the DM approach with unmatched projector and backprojector yielded a faster initial convergence when compared to the ideal full matrix approach. The analysis of the noise sources for the modeled single ring scanner in full matrix reconstruction showed that the noise introduced by the matrix became comparable to the noise introduced by the sinogram when using a matrix that was simulated with 10,000 emissions/voxel.

Algorithms↗

PubMed2005

A normal tissue dose response model of dynamic repair processes.

A model is presented for serial, critical element complication mechanisms for irradiated volumes from length scales of a few millimetres up to the entire organ. The central element of the model is the description of radiation complication as the failure of a dynamic repair process. The nature of the repair process is seen as reestablishing the structural organization of the tissue, rather than mere replenishment of lost cells. The interactions between the cells, such as migration, involved in the repair process are assumed to have finite ranges, which limits the repair capacity and is the defining property of a finite-sized reconstruction unit. Since the details of the repair processes are largely unknown, the development aims to make the most general assumptions about them. The model employs analogies and methods from thermodynamics and statistical physics. An explicit analytical form of the dose response of the reconstruction unit for total, partial and inhomogeneous irradiation is derived. The use of the model is demonstrated with data from animal spinal cord experiments and clinical data about heart, lung and rectum. The three-parameter model lends a new perspective to the equivalent uniform dose formalism and the established serial and parallel complication models. Its implications for dose optimization are discussed.

Animals↗

PubMed2005

Kinetic analysis of dynamic 18F-fluoromisonidazole PET correlates with radiation treatment outcome in head-and-neck cancer.

BACKGROUND: Hypoxia compromises local control in patients with head-and-neck cancer (HNC). In order to determine the value of [18F]-fluoromisonidazole (Fmiso) with regard to tumor hypoxia, a patient study with dynamic Fmiso PET was performed. For a better understanding of tracer uptake and distribution, a kinetic model was developed to analyze dynamic Fmiso PET data. METHODS: For 15 HNC patients, dynamic Fmiso PET examinations were performed prior to radiotherapy (RT) treatment. The data was analyzed using a two compartment model, which allows the determination of characteristic hypoxia and perfusion values. For different parameters, such as patient age, tumor size and standardized uptake value, the correlation to treatment outcome was tested using the Wilcoxon-Mann-Whitney U-test. Statistical tests were also performed for hypoxia and perfusion parameters determined by the kinetic model and for two different metrics based on these parameters. RESULTS: The kinetic Fmiso analysis extracts local hypoxia and perfusion characteristics of a tumor tissue. These parameters are independent quantities. In this study, different types of characteristic hypoxia-perfusion patterns in tumors could be identified. The clinical verification of the results, obtained on the basis of the kinetic analysis, showed a high correlation of hypoxia-perfusion patterns and RT treatment outcome (p = 0.001) for this initial patient group. CONCLUSION: The presented study established, that Fmiso PET scans may benefit from dynamic acquisition and analysis by a kinetic model. The pattern of distribution of perfusion and hypoxia in the tissue is correlated to local control in HNC.

Aged↗

PubMed2005

A pencil beam algorithm for intensity modulated proton therapy derived from Monte Carlo simulations.

A pencil beam algorithm as a component of an optimization algorithm for intensity modulated proton therapy (IMPT) is presented. The pencil beam algorithm is tuned to the special accuracy requirements of IMPT, where in heterogeneous geometries both the position and distortion of the Bragg peak and the lateral scatter pose problems which are amplified by the spot weight optimization. Heterogeneity corrections are implemented by a multiple raytracing approach using fluence-weighted sub-spots. In order to derive nuclear interaction corrections, Monte Carlo simulations were performed. The contribution of long ranged products of nuclear interactions is taken into account by a fit to the Monte Carlo results. Energy-dependent stopping power ratios are also implemented. Scatter in optional beam line accessories such as range shifters or ripple filters is taken into account. The collimator can also be included, but without additional scattering. Finally, dose distributions are benchmarked against Monte Carlo simulations, showing 3%/1 mm agreement for simple heterogeneous phantoms. In the case of more complicated phantoms, principal shortcomings of pencil beam algorithms are evident. The influence of these effects on IMPT dose distributions is shown in clinical examples.

Algorithms↗

PubMed2005

Robust treatment planning for intensity modulated radiotherapy of prostate cancer based on coverage probabilities.

BACKGROUND AND PURPOSE: To evaluate an optimization approach where coverage probabilities are incorporated into the optimization of intensity modulated radiotherapy (IMRT) to overcome the problem of margin definition in the case of overlapping planning target volume and organs at risk. PATIENTS AND METHODS: IMRT plans were generated for three optimization approaches: based on a planning CT plus margin (A), on prostate and rectum contours from five pre-treatment CT plus margin (B), and on coverage probabilities (C). For approach (C), the probability of organ occupation was computed for each voxel from five pre-treatment CTs and the population distribution of systematic setup error and it was used as local weight in the costfunctions. Monte Carlo simulations of treatment courses were used to compute the probability distribution of prostate and rectal wall equivalent uniform dose (EUD). RESULTS: Treatment simulations showed best and most robust results for prostate and rectal wall EUD within the population for (C). For (A) the rectal wall EUD was on average about 1.5 Gy greater than in (C), while the prostate EUD was lower than those from (C) for most of the patients for (B) (especially for those with great organ motion). CONCLUSIONS: The incorporation of coverage probabilities as local weights allows for dose escalation as well as improved rectal sparing and results in a safer and more robust IMRT treatment.

Computer Simulation↗

PubMed2005

Intensity modulated radiotherapy for high risk prostate cancer based on sentinel node SPECT imaging for target volume definition.

BACKGROUND: The RTOG 94-13 trial has provided evidence that patients with high risk prostate cancer benefit from an additional radiotherapy to the pelvic nodes combined with concomitant hormonal ablation. Since lymphatic drainage of the prostate is highly variable, the optimal target volume definition for the pelvic lymph nodes is problematic. To overcome this limitation, we tested the feasibility of an intensity modulated radiation therapy (IMRT) protocol, taking under consideration the individual pelvic sentinel node drainage pattern by SPECT functional imaging. METHODS: Patients with high risk prostate cancer were included. Sentinel nodes (SN) were localised 1.5-3 hours after injection of 250 MBq 99mTc-Nanocoll using a double-headed gamma camera with an integrated X-Ray device. All sentinel node localisations were included into the pelvic clinical target volume (CTV). Dose prescriptions were 50.4 Gy (5 x 1.8 Gy / week) to the pelvis and 70.0 Gy (5 x 2.0 Gy / week) to the prostate including the base of seminal vesicles or whole seminal vesicles. Patients were treated with IMRT. Furthermore a theoretical comparison between IMRT and a three-dimensional conformal technique was performed. RESULTS: Since 08/2003 6 patients were treated with this protocol. All patients had detectable sentinel lymph nodes (total 29). 4 of 6 patients showed sentinel node localisations (total 10), that would not have been treated adequately with CT-based planning ('geographical miss') only. The most common localisation for a probable geographical miss was the perirectal area. The comparison between dose-volume-histograms of IMRT- and conventional CT-planning demonstrated clear superiority of IMRT when all sentinel lymph nodes were included. IMRT allowed a significantly better sparing of normal tissue and reduced volumes of small bowel, large bowel and rectum irradiated with critical doses. No gastrointestinal or genitourinary acute toxicity Grade 3 or 4 (RTOG) occurred. CONCLUSION: IMRT based on sentinel lymph node identification is feasible and reduces the probability of a geographical miss. Furthermore, IMRT allows a pronounced sparing of normal tissue irradiation. Thus, the chosen approach will help to increase the curative potential of radiotherapy in high risk prostate cancer patients.

Aged↗

PubMed2005

Dose heterogeneity in the target volume and intensity-modulated radiotherapy to escalate the dose in the treatment of non-small-cell lung cancer.

PURPOSE: To quantify the dose escalation achievable in the treatment of non-small-cell lung cancer (NSCLC) by allowing dose heterogeneity in the target volume or using intensity-modulated radiotherapy (IMRT), or both. METHODS AND MATERIALS: Computed tomography data and contours of 10 NSCLC patients with limited movements of the tumor and representing a broad spectrum of clinical cases were selected for this study. Four irradiation techniques were compared: two conformal (CRT) and two IMRT techniques, either prescribing a homogeneous dose in the planning target volume (PTV) (CRT(hom) and IMRT(hom)) or allowing dose heterogeneity (CRT(inhom) and IMRT(inhom)). The dose heterogeneity was allowed only toward high doses, i.e., the minimum dose in the target for CRT(inhom) and IMRT(inhom) could not be lower than for the corresponding homogeneous plan. The dose in the PTV was escalated (fraction size of 2.25 Gy) until either an organ at risk reached the maximum allowed dose or the mean PTV dose reached a maximum level set at 101.25 Gy. RESULTS: When small and convex tumors were irradiated, CRT(hom) could achieve the maximum dose of 101.25 Gy, whereas for bigger and/or concave PTVs the dose level achievable with CRT(hom) was significantly lower, in 1 case even below 60 Gy. The CRT(inhom) allowed on average a 6% dose escalation with respect to CRT(hom). The IMRT(hom) achieved in all except 1 case a mean PTV dose of at least 75 Gy. The gain in mean PTV dose of IMRT(hom) with respect to CRT(hom) ranged from 7.7 to 14.8 Gy and the IMRT(hom) plans were always more conformal than the corresponding CRT(hom) plans. The IMRT(inhom) provided an additional advantage over IMRT(hom) of at least 5 Gy. For all CRT plans the achievable dose was determined by the lung dose threshold, whereas for more than half of the IMRT plans the esophagus was the dose-limiting organ. The IMRT plans were deliverable with 10-12 segments per beam and did not produce an increase of lung volume irradiated at low doses (<20 Gy). CONCLUSIONS: The dose in NSCLC treatments can be escalated by loosening the constraints on maximum dose in the target volume or using IMRT, or both. For large and concave tumors, an average dose escalation of 6% and 17% was possible when dose heterogeneity and IMRT were applied alone. When they were combined, the average dose increase was as high as 35%. Intensity-modulated RT delivered in a static mode can produce homogeneous dose distributions in the target and does not lead to an increase of lung volume receiving (very) low doses, even down to 5 Gy.

Carcinoma, Non-Small-Cell Lung↗

PubMed2005

A kinetic model for dynamic [18F]-Fmiso PET data to analyse tumour hypoxia.

A method is presented to identify and quantify hypoxia in human head-and-neck tumours based on dynamic [18F]-Fmiso PET patient data, using a model for the tracer transport. A compartmental model was developed, inspired by recent immunohistochemical investigations with the tracer pimonidazole. In order to take the trapping of the tracer and the diffusion in interstitial space into account, the kinetic model consists of two compartments and a specific input function. This voxel-based data analysis allows us to decompose the time-activity curves (TACs) into their perfusion, diffusion and hypoxia-induced retention components. This characterization ranges from well perfused tumours over diffusion limited hypoxia to strong hypoxia and necrosis. The overall shape of the TAC and the model parameters may point at the structural architecture of the tissue sample. The model addresses the two main problems associated with hypoxia imaging with PET. Firstly, the hypoxic areas are spatially separated from well perfused vessels, causing long diffusion times of the tracer. Secondly, tracer uptake occurs only in viable hypoxic cells, which constitute only a small subpopulation in the presence of necrosis. The resulting parameters such as the concentration of hypoxic cells and the perfusion are displayed in parameter plots ('hypoxia map'). Quantification of hypoxia performed with the presented kinetic model is more reliable than a criterion based on static standardized uptake values (SUV) at an early timepoint, because severely hypoxic/necrotic tissues show low uptake and are thus overlooked by SUV threshold identification. The derived independent measures for perfusion and hypoxia may provide a basis for individually adapted treatment planning.

Cell Hypoxia↗

PubMed2005

Dosimetric consequences of the application of off-line setup error correction protocols and a hull-volume definition strategy for intensity modulated radiotherapy of prostate cancer.

PURPOSE: To evaluate the consequences of a planning volume definition based on multiple CTs and the application of off-line setup error correction for the treatment of prostate cancer with intensity-modulated radiotherapy (IMRT). Further, to compare various setup correction protocols (SCP) by their influence on the average dose distributions. MATERIALS AND METHODS: A planning target volume (PTV) consisting of the bounding volume of prostate contours of five CTs (CTV_hull) plus an additional margin of 5mm and a virtual Rectum_hull volume (the solid bounding volume of the five corresponding rectum contours) are used for treatment planning. Simulations of treatment courses with the non-parametric bootstrap method allow to estimate the distribution of the expected equivalent uniform dose (EUD). The impact of off-line setup error correction protocols is evaluated based on estimated EUD distributions. RESULTS: Off-line SCP allow to achieve the intended prostate and rectum EUD and a reliable coverage of the CTV despite the reduced margins. The EUD of the virtual hull volumes is a good estimate for the EUD of prostate and rectal wall. CONCLUSION: Treatment planning based on Rectum_hull and CTV_hull plus setup margin as PTV in combination with SCP results in a robust and safe IMRT planning concept.

Humans↗

PubMed2004

Comparison between manual and automatic segment generation in step-and-shoot IMRT of prostate cancer.

PURPOSE: To compare two methods to generate treatment plans for intensity-modulated radiotherapy (IMRT) of prostate cancer, delivered in a step-and-shoot mode. The first method uses fluence optimization (inverse planning) followed by conversion of the fluence weight map into a limited number of segments. In the second method, segments are manually assigned using a class solution (forward planning), followed by computer optimization of the segment weights. METHODS: Treatment plans for IMRT, utilizing a simultaneous integrated boost, were created. Plans comprise a five-field technique to deliver 78 Gy to the prostate plus seminal vesicles. Five patients were evaluated. Optimization objectives of both planning approaches concerned dose coverage of the target volumes and the dose distribution in the rectal wall. The two methods were evaluated by comparing dose distributions, the complexity of the resulting plan and the time expenditure to generate and to deliver the plan. RESULTS: For both planning approaches 99% of the target volumes received 95% of the prescribed dose, which complies with our planning objectives. Inverse planning resulted in more conformal dose distributions than forward planning (conformity index: 1.37 versus 1.51). Inverse planning reduced the dose to the rectal wall compared to a manually designed plan, albeit to a small extent. The theoretical probability of severe rectal proctitis and/or stenosis was reduced on average by 1.9% with inverse planning. Maximal sparing of the rectal wall was achieved with inverse planning for a patient whose target volume was partly wrapped around the rectum. The number of segments generated with inverse planning ranged between 33 and 52, and between 9 and 13 segments for manually created segments. CONCLUSION: Dose coverage of the planning target volumes is adequate for both approaches of planning. Inverse planning results in slightly better dose distributions with respect to the rectal wall compared to manual planning, at the cost of an increase of the number of segments by a factor of 3.

Humans↗

PubMed2003

A revision of the gamma-evaluation concept for the comparison of dose distributions.

A method for the quantitative four-dimensional (4D) evaluation of discrete dose data based on gradient-dependent local acceptance thresholds is presented. The method takes into account the local dose gradients of a reference distribution for critical appraisal of misalignment and collimation errors. These contribute to the maximum tolerable dose error at each evaluation point to which the local dose differences between comparison and reference data are compared. As shown, the presented concept is analogous to the gamma-concept of Low et al (1998a Med. Phys. 25 656-61) if extended to (3+1) dimensions. The pointwise dose comparisons of the reformulated concept are easier to perform and speed up the evaluation process considerably, especially for fine-grid evaluations of 3D dose distributions. The occurrences of false negative indications due to the discrete nature of the data are reduced with the method. The presented method was applied to film-measured, clinical data and compared with gamma-evaluations. 4D and 3D evaluations were performed. Comparisons prove that 4D evaluations have to be given priority, especially if complex treatment situations are verified, e.g., non-coplanar beam configurations.

Algorithms↗

PubMed2003

A comparison of forward and inverse treatment planning for intensity-modulated radiotherapy of head and neck cancer.

BACKGROUND AND PURPOSE: To compare intensity-modulated treatment plans of patients with head and neck cancer generated by forward and inverse planning. MATERIALS AND METHODS: Ten intensity-modulated treatment plans, planned and treated with a step&shoot technique using a forward planning approach, were retrospectively re-planned with an inverse planning algorithm. For this purpose, two strategies were applied. First, inverse planning was performed with the same beam directions as forward planning. In addition, nine equidistant, coplanar incidences were used. The main objective of the optimisation process was the sparing of the parotid glands beside an adequate treatment of the planning target volume (PTV). Inverse planning was performed both with pencil beam and Monte Carlo dose computation to investigate the influence of dose computation on the result of the optimisation. RESULTS: In most cases, both inverse planning strategies managed to improve the treatment plans distinctly due to a better target coverage, a better sparing of the parotid glands or both. A reduction of the mean dose by 3-11Gy for at least one of the parotid glands could be achieved for most of the patients. For three patients, inverse planning allowed to spare a parotid gland that had to be sacrificed by forward planning. Inverse planning increased the number of segments compared to forward planning by a factor of about 3; from 9-15 to 27-46. No significant differences for PTV and parotid glands between both inverse planning approaches were found. Also, the use of Monte Carlo instead of pencil beam dose computation did not influence the results significantly. CONCLUSION: The results demonstrate the potential of inverse planning to improve intensity-modulated treatment plans for head and neck cases compared to forward planning while retaining clinical utility in terms of treatment time and quality assurance.

Head and Neck Neoplasms↗

PubMed2003

[Fluence-modulated radiotherapy with an optimization-integrated sequencer].

On the basis of two clinical cases, we present fluence-modulated radiotherapy with a sequencer integrated into the optimization of our treatment-planning software HYPERION. In each case, we achieved simple relations for the dependence of the total number of segments on the complexity of the sequencing, as well as for the dependence of the dose-distribution quality on the number of segments. For both clinical cases, it was possible to obtain treatment plans that complied with the clinical demands on dose distribution and number of segments. Also, compared to the widespread concept of equidistant steps, our method of sequencing with fluence steps of variable size led to a significant reduction of the number of segments, while maintaining the quality of the dose distribution. Our findings substantiate the value of the integration of the sequencer into the optimization for the clinical efficiency of IMRT.

Humans↗

PubMed2002

[A concept for the optimization of clinical IMRT].

The present paper introduces a concept for the description of treatment objectives of IMRT which emphasizes the assurance of an acceptable dose distribution in risk organs. A number of DVH manipulation tools are available to take into account both the volume effects of normal tissue and the influence of dose fractionation. The optimization of the dose distribution strictly obeys the prescribed risks of complications, as well as the limits of dose homogeneity in the target volume. The application of IMRT is made more efficient by limiting the modulation of the fluence profiles. The use of this algorithm could simplify IMRT in a way that a larger number of patients can profit from this type of treatment.

Humans↗