Biomedical subjects

Fridtjof Nüsslin

Publications and source records attributed to Fridtjof Nüsslin.

18 recordsLinked to original sources

PubMed2006

High-precision radiation therapy with integrated biological imaging and tumor monitoring: evolution of the Munich concept and future research options.

PURPOSE: To describe an emerging concept of high-precision radiotherapy, a modality characterized by adaptation to patient and organ movements, which might occur between fractions or even during radiation delivery. METHODS AND RESULTS: Today's unprecedented technical capabilities to visualize the target volume and create conformal dose distributions allow for avoidance of critical structures or targeted treatment intensification within a conventionally imaged, anatomically defined tumor. The success of selective dose escalation depends on (1) correct staging and target volume identification, which can be improved by biological imaging, and (2) identification of biologically relevant subvolumes, which determine tumor control. Current efforts are directed at different methods, such as positron emission tomography and magnetic resonance spectroscopy, and integrating them into treatment planning. CONCLUSION: Early clinical trials assessing the safety and efficacy of image- and biology-guided radiotherapy are ongoing. The same modalities might be used to determine the individual tumor response during treatment and to adapt therapy. Temporal changes in tumor biology, which might represent both a challenge and a chance with regard to adaptation of treatment, need to be addressed in greater detail.

Animals↗

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↗

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

Off-axis chamber response in the depth of photon dose maximum.

Measurements as well as Monte Carlo simulations are presented to investigate the deviation between the dose to water and the value measured by an ionization chamber. These deviations are evaluated at different depths (1.5 and 10 cm) and at an off-axis position of 15 cm. It is shown that an ionization chamber can produce a measuring signal, which is up to 2.5% too low, compared to the dose, when measurements are performed at shallow depths and far off-axis. The reason for this underresponse is found in the variation of the wall correction factor. As a result of the variation of the radiation spectra with depth and position the dose to the air volume, which originates from the wall, varies and therefore changes the wall correction factor.

Calibration↗

PubMed2005

Clinical quality assurance for 106Ru ophthalmic applicators.

BACKGROUND AND PURPOSE: Episcleral brachytherapy using 106Ru/106Rh ophthalmic applicators is a proven method of therapy of uveal melanomas sparing the globe and in many cases sparing the vision. In the year 2001, an internal clinical quality assurance procedure revealed that part of the ophthalmic applicators leaked and that the calibration was erroneous. Consequently, the producer modernized its production procedures and, in May 2002, introduced a dose rate calibration that is traceable to the NIST standard. This NIST calibration confirmed that the previous calibration had been incorrect. In order to study the effects of the producer's new internal quality assurance procedures on the ophthalmic applicators, applicators of this new generation were submitted to a newly improved internal clinical acceptance test. PATIENTS AND METHODS: The internal clinical acceptance test consists of a leakage test and a dosimetric test of the ophthalmic applicators. The leakage test simulates contact of the ophthalmic applicators with chloride containing body fluid. The dosimetric tests measure depth dose curves and dose rate with a plastic scintillator dosimetric system and compare them with the indications in the producer's certificate. Furthermore, the depth dose profile of the most frequently used applicator (type CCB) was compared with published data. RESULTS: The internal clinical leakage test showed that all of the tested ophthalmic applicators belonging to the new generation (n=17) were tight and not contaminated. The dosimetric acceptance tests applied to seven different types of applicators revealed that the relative depth dose profiles in the therapeutically relevant range (up to a depth of <or=7 mm) deviate from the producer's indications only by -2.7 to +3.2%. The acceptance test of the dose rate values of the ophthalmic applicators at a distance of 2mm from the surface of the applicators resulted in a coefficient of variation of 1.7% (n=17). In the evaluation of the depth dose profile of the type CCB applicator the producer's indications and the results of the entrance test conformed very well to published data. CONCLUSIONS: The internal clinical quality assurance procedure has proved successful in three ways. (1) It had a catalytic effect that led to the development of a new generation of ophthalmic applicators. (2) It could be demonstrated that this new generation of applicators is up to the state of the art in brachytherapy. (3) With this new generation of 106Ru/106Rh ophthalmic applicators it is possible for the first time in the history of their use to apply the dose that is prescribed by the radiooncologist.

Brachytherapy↗

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

Study on the tongue and groove effect of the Elekta multileaf collimator using Monte Carlo simulation and film dosimetry.

BACKGROUND: Nowadays, multileaf collimation of the treatment fields from medical linear accelerators is a common option. Due to the design of the leaf sides, the tongue and groove effect occurs for certain multileaf collimator applications such as the abutment of fields where the beam edges are defined by the sides of the leaves. MATERIAL AND METHODS: In this study, the tongue and groove effect was measured for two pairs of irregular multileaf collimator fields that were matched along leaf sides in two steps. Measurements were made at 10 cm depth in a polystyrene phantom using Kodak EDR2 films for a photon beam energy of 6 MV on an Elekta Sli-plus accelerator. To verify the measurements, full Monte Carlo simulations were done. In the simulations, the design of the leaf sides was taken into account and one component module of BEAM code was modified to correctly simulate the Elekta multileaf collimator. RESULTS AND CONCLUSION: The results of measurements and simulations are in good agreement and within the tolerance of film dosimetry.

Computer Simulation↗

PubMed2004

On the actual state of industrial quality assurance procedures with regard to (106)Ru ophthalmic plaques.

BACKGROUND: In radiotherapy of intraocular tumors, e. g., in the case of malign choroid melanomas, episcleral brachytherapy with (106)Ru ophthalmic plaques has proven to be successful. In a study, the authors reported on the discovery of the following shortcomings in industrial quality assurance, which are relevant to therapy, during the course of an internal clinical acceptance test of (106)Ru ophthalmic plaques, manufactured by the company Bebig from Berlin, Germany. This consisted of inconsistent dose rate specifications in the manufacturer's certificate, covering a range of 111% and with the risk of leakage of the plaques. Bebig was called upon to adapt state-of-the-art production methods with regard to (106)Ru ophthalmic plaques. MATERIAL AND METHODS: In the meantime, Bebig has modernized production of (106)Ru ophthalmic plaques and adopted all the quality assurance procedures proposed by the authors. Moreover, the requested traceability of the calibration of activity and dose rate of the (106)Ru ophthalmic plaques to standards of the federal authorities in charge of measurement procedures has been implemented. RESULTS: In the year 2002, Bebig updated, among other things, the ASMW (GDR) calibration of the dose rate of the (106)Ru ophthalmic plaques from the years 1987-1989 by a calibration of the NIST (USA). The current NIST calibration, together with the new equipment for the measurement of the depth dose curves, led to the consequence that the new NIST 2001 dose rate values show, in the mean, a deviation of 0.75 times (plaque type CCC) up to 2.06 times (plaque types CCX, CCY, and CCZ) compared to the dose rate values that had been indicated so far in Bebig's certificate, based on the ASMW 1987 calibration. For the 95% confidence interval, Bebig estimated the measurement uncertainty to be +/- 25%. If one takes into consideration the minimal and maximal values in such 95% confidence intervals, it follows that the new NIST 2001 dose rate values deviate between 0.56 times (plaque type CCC) and 2.58 times (plaque types CCX, CCY, and CCZ) from the Bebig certificate (ASMW calibration 1987). As regards leakage, no objections arose in the case of the (106)Ru ophthalmic plaques produced according to the new quality standards. CONCLUSION: Legislation has to make sure that the use of radioactive material on humans be, among other things, permitted as a matter of principle only, if the dose rate calibration can be traced to standards of a federal authority of measurement procedures. Furthermore, special leakage tests for radiation sources which come into direct contact with body fluids should be established. A historical retrospect reveals that the greatest changes have taken place in the indication of the dose rates of (125)I sources. Since the beginning of the use of (125)I sources in brachytherapy in the late 1960s, the dose rate indications, so far, have had to be reduced in small steps over a period of about 35 years by nearly a factor of 2. As regards the (106)Ru ophthalmic plaques, the NIST 2001 calibration has resulted in a comparable reduction of the dose rate indications of up to a factor of 2 within the period of about several months. Thus, in the previous history of radiotherapy this case must be regarded as unique, because for the first time ever, an urgently needed recalibration has been protracted for such an unduly long period of time.

Calibration↗

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

Smoothing Monte Carlo calculated dose distributions by iterative reduction of noise.

A smoothing algorithm based on an optimization procedure is presented and evaluated for single electron and photon beams and a full intensity modulated radiation therapy (IMRT) delivery. The algorithm iteratively reduces the statistical noise of Monte Carlo (MC) calculated dose distributions. It is called IRON (iterative reduction of noise). By varying the dose in each voxel, the algorithm minimizes the second partial derivatives of dose with respect to X, Y and Z. An additional restoration term ensures that too large dose changes are prevented. IRON requires a MC calculated one-dimensional or three-dimensional dose distribution with or without known statistical uncertainties as input. The algorithm is tested using three different treatment plan examples, a photon beam dose distribution in water, an IMRT plan of a real patient and an electron beam dose distribution in a water phantom with inhomogeneities. It is shown that smoothing can lead to an additional reduction of MC calculation time by factors of 2 to 10. This is especially useful if MC dose calculation is part of an inverse treatment planning system. In addition to this, it is shown that smoothing a noisy dose distribution may introduce some bias into the final dose values by converting the statistical uncertainty of the dose distribution into a systematic deviation of the dose value.

Algorithms↗

PubMed2003

Monte Carlo dose calculations in the treatment of a pelvis with implant and comparison with pencil-beam calculations.

In the present paper, dose distribution calculated with the Monte Carlo code EGS4 and with a pencil-beam algorithm are compared for the treatment of a pelvis with an implant. Overestimations of dose values inside the target volume by the pencil-beam algorithm of up to 10% were found, which are attributed to the underestimation of the absorption of photons by the implant. The differences in dose distributions are also expressed by comparing the tumor control probability (TCP) of the Monte Carlo dose calculations with the TCP of the pencil-beam calculations. A TCP reduction of order of 30% was found.

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↗

PubMed2003

A virtual photon energy fluence model for Monte Carlo dose calculation.

The presented virtual energy fluence (VEF) model of the patient-independent part of the medical linear accelerator heads, consists of two Gaussian-shaped photon sources and one uniform electron source. The planar photon sources are located close to the bremsstrahlung target (primary source) and to the flattening filter (secondary source), respectively. The electron contamination source is located in the plane defining the lower end of the filter. The standard deviations or widths and the relative weights of each source are free parameters. Five other parameters correct for fluence variations, i.e., the horn or central depression effect. If these parameters and the field widths in the X and Y directions are given, the corresponding energy fluence distribution can be calculated analytically and compared to measured dose distributions in air. This provides a method of fitting the free parameters using the measurements for various square and rectangular fields and a fixed number of monitor units. The next step in generating the whole set of base data is to calculate monoenergetic central axis depth dose distributions in water which are used to derive the energy spectrum by deconvolving the measured depth dose curves. This spectrum is also corrected to take the off-axis softening into account. The VEF model is implemented together with geometry modules for the patient specific part of the treatment head (jaws, multileaf collimator) into the XVMC dose calculation engine. The implementation into other Monte Carlo codes is possible based on the information in this paper. Experiments are performed to verify the model by comparing measured and calculated dose distributions and output factors in water. It is demonstrated that open photon beams of linear accelerators from two different vendors are accurately simulated using the VEF model. The commissioning procedure of the VEF model is clinically feasible because it is based on standard measurements in air and water. It is also useful for IMRT applications because a full Monte Carlo simulation of the treatment head would be too time-consuming for many small fields.

Computer Simulation↗

PubMed2002

[Positioning accuracy in conformational prostatic irradiation using portal imaging].

BACKGROUND: Conformal radiotherapy techniques as used in prostate treatment allow to spare normal tissue by conforming the radiation fields to the shape of the planning target volume (PTV). To be able to fully utilize the advantages of these techniques correct patient positioning is an important prerequisite. This study employing an electronic portal imaging device (EPID) investigated the positioning uncertainties that occur in the pelvic region for different patient positioning devices. PATIENTS AND METHODS: 15 patients with prostate cancer were irradiated with or without rectal balloon/pelvic mask at a linear accelerator with multileaf collimator (MLC). For each patient multiple portal images were taken from different directions and compared to the digitally reconstructed radiographs (DRRs) of the treatment planning system and to simulation films (Table 1, Figure 1). RESULTS: In spite of different positioning devices, all patients showed comparable total positioning uncertainties of 4.0 mm (lateral), 4.5 mm (cranio-caudal) and 1.7 mm (dorso-ventral). The lateral positioning error was reduced for the pelvic mask patients while the cranio-caudal error increased (Table 2, Figure 2). A systematic and a random component sum up to the total positioning error, and a good estimate of the magnitudes of the two is possible from six to eight portal images (Figure 3). CONCLUSIONS: With a small number of portal images it is possible to find out the systematic and random positioning error of a patient. Knowledge of the random error can be used to resize the treatment margin which is clinically relevant since this error differs greatly for different patients (Figure 4). Image analysis with EPID is convenient, yet has some problems. For example, one only gets indirect information on the movement of the ventral rectum wall (Figure 5). The successful operation of positioning devices, although, needs further improvement--especially if one focuses on IMRT.

Artifacts↗

PubMed2002

[Physical and technical quality assurance and radiation protection in transperineal interstitial permanent prostate brachytherapy with 125-iodine seeds].

BACKGROUND: Early stage prostate cancer can be treated successfully by interstitial brachytherapy with 125-iodine seeds. A quality-assurance programme is presented that was designed for this purpose for internal clinical use. Furthermore the requirements of the new German Ordinance Governing Radiation Protection (StrlSchV) that came into force on August 1, 2001, are taken into account. MATERIAL AND METHODS: For the 125-iodine monotherapy of the prostate we used RAPID STRANDS (Amersham Health, Braunschweig, Germany). According to the guidelines of the new Ordinance Governing Radiation Protection, the determination of the body dose of the staff is made to rely on the new measurement quantities H(p) (10) and H(p) (0.07). The nominal air kerma rate of the seeds is measured with a calibrated well-chamber of the type HDR 1000 Plus and an electrometer of the type MAX 4000 (Standard Imaging Inc., USA). The ultrasound images of the prostate are produced by an ultrasound device of the type Falcon 2101 (B-K Medical, Denmark). For treatment planning the programme VariSeed (Varian, Darmstadt, Germany) was employed. Correct loading of the needles is controlled by autoradiography before implantation. After the implantation radiation-protection measurements in the operating room are carried out. RESULTS: As regards the personnel, for the depth personal dose equivalent Hp(10) and relating to two applications each, measurement values between 0 microSv and 14 microSv resulted. The control of the radiation exposure of the hands revealed superficial personal dose values H(p) (0.07) of up to 1 mSv. The nominal air kerma rates of the RAPID STRANDS were all lying within the 95% confidence interval guaranteed by the producer. The autoradiographs documented -- except for one case -- the correct loading of the needles. The interstitial transperineal prostate implantation of the 125-iodine seeds succeeded as planned with all patients. Until now no contamination of the operating room was detected by the radiation-protection measurements. CONCLUSION: The physical-technical quality assurance programme presented here covers the whole physical-technical range of the internal clinical quality assurance and could be integrated into the course of the treatment without any problems. It has th following advantages: The autoradiographic documentation of the correctly loaded needles serves as proof that the prerequisite for the production of the prescribed physical dose distribution is fulfilled. The internal clinical determination of the nominal air kerma rate is the basis for a correct dose application.

Brachytherapy↗

PubMed2002

[Physical basics and clinical realization of interstitial brachytherapy of the prostate with iodine 125].

BACKGROUND: Interstitial brachytherapy with I-125 seeds can be used for successful treatment of early stage prostate cancer. There is presented the technique of permanent transperineal implantation of I-125 seeds with intraoperative treatment planning which is suited for the treatment of prostate cancer up to the clinical stage of T2a. MATERIAL AND METHODS: Some weeks before the implantation of the seeds the prostate volume is determined using transrectal ultrasound (TRUS) so as to estimate the required number of I-125 seeds. At the outset of the treatment the prostate is stabilized by two perineally inserted needles. Subsequently there is carried out an ultrasound guided treatment planning that allows to optimize the distribution of the seeds within the prostate. In interstitial brachytherapy we use RAPID STRANDS((R)), i. e. the I-125 seeds are embedded in vicryl suture at distances of 1 cm. During implantation of the I-125 seeds the transversal placement of the applicator needles is controlled by TRUS and the cranio-caudal placement of the applicator needles is controlled using the fluoroscopic unit as well as TRUS. About 4 weeks after the implantation of the seeds there is carried out a postoperative computation of the dose distribution of the implant using CT imaging. RESULTS: The procedure possesses the advantage that ultrasound imaging, treatment planning and seed implantation are carried out with the prostate remaining in an unaltered position. During implantation the combined imaging of TRUS and fluoroscopy allows a safe placement of the seeds with in the prostate. CONCLUSION: The methods for the calculation of the actually attained dose distribution must still be optimized, because the postoperative examination of the individual results has so far been possible only with difficulties resulting from methodological inconveniences.

Aged↗

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↗