Thorsten Frenzel

An optical flow based method for improved reconstruction of 4D CT data sets acquired during free breathing

Respiratory motion degrades anatomic position reproducibility and leads to issues affecting image acquisition, treatment planning, and radiation delivery. Four-dimensional (4D) computer tomography (CT) image acquisition can be used to measure the impact of organ motion and to explicitly account for respiratory motion during treatment planning and radiation delivery. Modern CT scanners can only scan a limited region of the body simultaneously and patients have to be scanned in segments consisting of multiple slices. A respiratory signal (spirometer signal or surface tracking) is used to reconstruct a 4D data set by sorting the CT scans according to the couch position and signal coherence with predefined respiratory phases. But artifacts can occur if there are no acquired data segments for exactly the same respiratory state for all couch positions. These artifacts are caused by device-dependent limitations of gantry rotation, image reconstruction times and by the variability of the patients respiratory pattern. In this paper an optical flow based method for improved reconstruction of 4D CT data sets from multislice CT scans is presented. The optical flow between scans at neighboring respiratory states is estimated by a non-linear registration method. The calculated velocity field is then used to reconstruct a 4D CT data set by interpolating data at exactly the predefined respiratory phase. Our reconstruction method is compared with the usually used reconstruction based on amplitude sorting. The procedures described were applied to reconstruct 4D CT data sets for four cancer patients and a qualitative and quantitative evaluation of the optical flow based reconstruction method was performed. Evaluation results show a relevant reduction of reconstruction artifacts by our technique. The reconstructed 4D data sets were used to quantify organ displacements and to visualize the abdominothoracic organ motion.

Contrast-Enhanced [18F]fluorodeoxyglucose-Positron Emission Tomography/Computed Tomography for Staging and Radiotherapy Planning in Patients With Anal Cancer

PURPOSE The practice of surgical staging and treatment of anal cancer has been replaced by noninvasive staging and combined modality therapy. For appropriate patient management, accurate lymph node staging is crucial. The present study evaluated the feasibility and diagnostic accuracy of contrast-enhanced [(18)F]fluoro-2-deoxy-d-glucose ([(18)F]FDG)-positron emission tomography/computed tomography (PET/CT) for staging and radiotherapy planning of anal cancer. METHODS AND MATERIALS A total of 22 consecutive patients (median age, 61 years old) with anal cancer underwent complete staging evaluation including physical examination, biopsy of the primary tumor, and contrast-enhanced (ce)-PET/CT. Patients were positioned as they would be for their subsequent radiotherapy. PET and CT images were evaluated independently for detectability and localization of the primary tumor, pelvic and inguinal lymph nodes, and distant metastasis. The stage, determined by CT or PET alone, and the proposed therapy planning were compared with the stage and management determined by ce-PET/CT. Data from ce-PET/CT were used for radiotherapy planning. RESULTS ce-PET/CT revealed locoregional lymph node metastasis in 11 of 22 patients (50%). After simultaneous reading of PET and CT data sets by experienced observers, 3 patients (14%) were found to have sites of disease not seen on CT that were identified on PET. Two patients had sites of disease not seen on PET that were identified on CT. In summary, 2 patients were upstaged, and 4 patients were downstaged due to ce-PET/CT. However, radiotherapy fields were changed due to the results from ce-PET/CT in 23% of cases compared to CT or PET results alone. CONCLUSIONS ce-PET/CT is superior to PET or CT alone for staging of anal cancer, with significant impact on therapy planning.

4D medical image computing and visualization of lung tumor mobility in spatio-temporal CT image data

The development of 4D CT imaging has introduced the possibility of measuring breathing motion of tumors and inner organs. Conformal thoracic radiation therapy relies on a quantitative understanding of the position of lungs, lung tumors, and other organs during radiation delivery. Using 4D CT data sets, medical image computing and visualization methods were developed to visualize different aspects of lung and lung tumor mobility during the breathing cycle and to extract quantitative motion parameters. A non-linear registration method was applied to estimate the three-dimensional motion field and to compute 3D point trajectories. Specific visualization techniques were used to display the resulting motion field, the tumors appearance probabilities during a breathing cycle as well as the volume covered by the moving tumor. Furthermore, trajectories of the tumor center-of-mass and organ specific landmarks were computed for the quantitative analysis of tumor and organ motion. The analysis of 4D data sets of seven patients showed that tumor mobility differs significantly between the patients depending on the individual breathing pattern and tumor location.

Towards accurate dose accumulation for Step-&-Shoot IMRT: Impact of weighting schemes and temporal image resolution on the estimation of dosimetric motion effects.

PURPOSE Breathing-induced motion effects on dose distributions in radiotherapy can be analyzed using 4D CT image sequences and registration-based dose accumulation techniques. Often simplifying assumptions are made during accumulation. In this paper, we study the dosimetric impact of two aspects which may be especially critical for IMRT treatment: the weighting scheme for the dose contributions of IMRT segments at different breathing phases and the temporal resolution of 4D CT images applied for dose accumulation. METHODS Based on a continuous problem formulation a patient- and plan-specific scheme for weighting segment dose contributions at different breathing phases is derived for use in step-&-shoot IMRT dose accumulation. Using 4D CT data sets and treatment plans for 5 lung tumor patients, dosimetric motion effects as estimated by the derived scheme are compared to effects resulting from a common equal weighting approach. Effects of reducing the temporal image resolution are evaluated for the same patients and both weighting schemes. RESULTS The equal weighting approach underestimates dosimetric motion effects when considering single treatment fractions. Especially interplay effects (relative misplacement of segments due to respiratory tumor motion) for IMRT segments with only a few monitor units are insufficiently represented (local point differences >25% of the prescribed dose for larger tumor motion). The effects, however, tend to be averaged out over the entire treatment course. Regarding temporal image resolution, estimated motion effects in terms of measures of the CTV dose coverage are barely affected (in comparison to the full resolution) when using only half of the original resolution and equal weighting. In contrast, occurence and impact of interplay effects are poorly captured for some cases (large tumor motion, undersized PTV margin) for a resolution of 10/14 phases and the more accurate patient- and plan-specific dose accumulation scheme. CONCLUSIONS Radiobiological consequences of reported single fraction local point differences >25% of the prescribed dose are widely unclear and should be subject to future investigation. Meanwhile, if aiming at accurate and reliable estimation of dosimetric motion effects, precise weighting schemes such as the presented patient- and plan-specific scheme for step-&-shoot IMRT and full available temporal 4D CT image resolution should be applied for IMRT dose accumulation.

Detection rate of PET/CT in patients with biochemical relapse of prostate cancer using [ 68 Ga]PSMA I&T and comparison with published data of [ 68 Ga]PSMA HBED-CC

PurposeTo determine the detection rate of PET/CT in biochemical relapse of prostate cancer using [68Ga]PSMA I&T and to compare it with published detection rates of [68Ga]PSMA HBED-CC.MethodsWe performed a retrospective analysis in 83 consecutive patients with documented biochemical relapse after prostatectomy. All patients underwent whole body [68Ga]PSMA I&T PET/CT. PET/CT images were evaluated for presence of local recurrence, lymph node metastases, and distant metastases. Proportions of positive PET/CT results were calculated for six subgroups with increasing prostate specific antigen (PSA) levels (<0.5 ng/mL, 0.5 to <1.0 ng/mL, 1.0 to <2.0 ng/mL, 2.0 to <5.0 ng/mL, 5.0 to <10.0, ≥10.0 ng/mL). Detection rates of [68Ga]PSMA I&T were statistically compared with published detection rates of [68Ga]PSMA HBED-CC using exact Fisher’s test.ResultsMedian PSA was 0.81 (range: 0.01 – 128) ng/mL. In 58/83 patients (70 %) at least one [68Ga]PSMA I&T positive lesion was detected. Local recurrent cancer was present in 18 patients (22 %), lymph node metastases in 29 patients (35 %), and distant metastases in 15 patients (18 %). The tumor detection rate was positively correlated with PSA levels, resulting in detection rates of 52 % (<0.5 ng/mL), 55 % (0.5 to <1.0 ng/mL), 70 % (1.0 to <2.0 ng/mL), 93 % (2.0 to <5.0 ng/mL), 100 % (5.0 to <10.0 ng/mL), and 100 % (≥10.0 ng/mL). There was no significant difference between the detection rate of [68Ga]PSMA I&T and published detection rates of [68Ga]PSMA HBED-CC (all p>0.05).Conclusions[68Ga]PSMA I&T PET/CT has high detection rates of recurrent prostate cancer that are comparable to [68Ga]PSMA HBED-CC.

Analysis of free breathing motion using artifact reduced 4D CT image data

The mobility of lung tumors during the respiratory cycle is a source of error in radiotherapy treatment planning. Spatiotemporal CT data sets can be used for studying the motion of lung tumors and inner organs during the breathing cycle. We present methods for the analysis of respiratory motion using 4D CT data in high temporal resolution. An optical flow based reconstruction method was used to generate artifact-reduced 4D CT data sets of lung cancer patients. The reconstructed 4D CT data sets were segmented and the respiratory motion of tumors and inner organs was analyzed. A non-linear registration algorithm is used to calculate the velocity field between consecutive time frames of the 4D data. The resulting velocity field is used to analyze trajectories of landmarks and surface points. By this technique, the maximum displacement of any surface point is calculated, and regions with large respiratory motion are marked. To describe the tumor mobility the motion of the lung tumor center in three orthogonal directions is displayed. Estimated 3D appearance probabilities visualize the movement of the tumor during the respiratory cycle in one static image. Furthermore, correlations between trajectories of the skin surface and the trajectory of the tumor center are determined and skin regions are identified which are suitable for prediction of the internal tumor motion. The results of the motion analysis indicate that the described methods are suitable to gain insight into the spatiotemporal behavior of anatomical and pathological structures during the respiratory cycle.

Partial body irradiation of small laboratory animals with an industrial X-ray tube

AIMS Dedicated precise small laboratory animal irradiation sources are needed for basic cancer research and to meet this need expensive high precision radiation devices have been developed. To avoid such expenses a cost efficient way is presented to construct a device for partial body irradiation of small laboratory animals by adding specific components to an industrial X-ray tube. METHODS AND MATERIALS A custom made radiation field tube was added to an industrial 200 kV X-ray tube. A light field display as well as a monitor ionization chamber were implemented. The field size can rapidly be changed by individual inserts of MCP96 that are used for secondary collimation of the beam. Depth dose curves and cross sectional profiles were determined with the use of a custom made water phantom. More components like positioning lasers, a custom made treatment couch, and a commercial isoflurane anesthesia unit were added to complete the system. RESULTS With the accessories described secondary small field sizes down to 10 by 10 mm2 (secondary collimator size) could be achieved. The dosimetry of the beam was constructed like those for conventional stereotactical clinical linear accelerators. The water phantom created showed an accuracy of 1 mm and was well suited for all measurements. With the anesthesia unit attached to the custom made treatment couch the system is ideal for the radiation treatment of small laboratory animals like mice. CONCLUSION It was feasible to shrink the field size of an industrial X-ray tube from whole animal irradiation to precise partial body irradiation of small laboratory animals. Even smaller secondary collimator sizes than 10 by 10 mm2 are feasible with adequate secondary collimator inserts. Our custom made water phantom was well suited for the basic dosimetry of the X-ray tube.

Design, performance characteristics and application examples of a new 4D motion platform.

In this publication, a three-dimensionally movable motion phantom is described and its performance characteristics are evaluated. The intended primary fields of application for the phantom are the quality assurance (QA) of respiratory motion management devices in radiation therapy (RT) like gating or tumour tracking systems, training for clinical use of these techniques, and related 4DRT research. Considering especially the QA aspect, the phantom was designed as a motion platform that can be equipped with an appropriate add-on like standard QA phantoms for dosimetric measurements. The platform is driven by three computer-controlled independent linear motors (motion range: 40 × 50 × 50 mm in anterior-posterior/superior-inferior/lateral direction; max. velocity: 3.9 m/s; max. acceleration: 10 m/s(2)), which allow the simulation of normal breathing patterns as well as arbitrary trajectories and anomalous events like coughing or baseline drift. For normal breathing patterns (here: sinusoidal curves with an amplitude of 20mm and a period of 3 s/6 s), the accuracy of the simulated motion paths was measured to be within 0,521 mm even for the ArcCHECK (weight: 20 kg) as a platform load - values that we consider to be sufficient for the intended fields of application. The respective use of the motion phantom is illustrated.

Magnetic resonance imaging for precise radiotherapy of small laboratory animals

AIMS Radiotherapy of small laboratory animals (SLA) is often not as precisely applied as in humans. Here we describe the use of a dedicated SLA magnetic resonance imaging (MRI) scanner for precise tumor volumetry, radiotherapy treatment planning, and diagnostic imaging in order to make the experiments more accurate. METHODS AND MATERIALS Different human cancer cells were injected at the lower trunk of pfp/rag2 and SCID mice to allow for local tumor growth. Data from cross sectional MRI scans were transferred to a clinical treatment planning system (TPS) for humans. Manual palpation of the tumor size was compared with calculated tumor size of the TPS and with tumor weight at necropsy. As a feasibility study MRI based treatment plans were calculated for a clinical 6MV linear accelerator using a micro multileaf collimator (μMLC). In addition, diagnostic MRI scans were used to investigate animals which did clinical poorly during the study. RESULTS MRI is superior in precise tumor volume definition whereas manual palpation underestimates their size. Cross sectional MRI allow for treatment planning so that conformal irradiation of mice with a clinical linear accelerator using a μMLC is in principle feasible. Several internal pathologies were detected during the experiment using the dedicated scanner. CONCLUSION MRI is a key technology for precise radiotherapy of SLA. The scanning protocols provided are suited for tumor volumetry, treatment planning, and diagnostic imaging.

High Accuracy of Virtual Simulation with the Laser System Dorado CT4

Purpose:To evaluate the accuracy of virtual simulation, which is less time-consuming than physical simulation, with the new laser system Dorado CT4 in 96 prostate cancer patients.Patients and Methods:Virtual simulation was based on a spiral scan with 8 mm reconstruction index and 8 mm slice thickness in 64 patients (group A), and 3 mm reconstruction index and 3 mm slice thickness in 32 patients (group B). Both groups were evaluated for impact on maximum difference (Δmax) regarding the isocenters obtained from virtual simulation versus those obtained from physical simulation.Results:In the entire cohort, mean differences were as follows: Δmax 5.7 ± 3.5 mm, Δx (left/right) 2.8 ± 2.9 mm, Δy (anterior/posterior) 4.5 ± 3.8 mm, and Δz (cranial/caudal) 2.1 ± 2.2 mm. In group A, mean values were Δmax 6.2 ± 3.8 mm, Δx 2.9 ± 3.1 mm, Δy 4.9 ± 4.2 mm, and Δz 2.3 ± 2.3 mm. In group B, mean values were Δmax 4.8 ± 2.8 mm, Δx 2.7 ± 2.7 mm, Δy 3.7 ± 2.7 mm, and Δz 1.7 ± 2.0 mm. Time of radiotherapy (primary vs. salvage RT) and radiation regimen (external-beam radiotherapy [EBRT] vs. high-dose-rate brachytherapy [HDR-BT] plus EBRT) had no significant impact on Δmax.Conclusion:Virtual simulation with the new laser system Dorado CT4 was very precise for both primary and salvage RT in the treatment of prostate cancer patients. High precision was achieved for both EBRT and HDR-BT plus EBRT. Virtual simulation should be performed with a planning CT with 3 mm reconstruction index and 3 mm slice thickness for high accuracy.Hintergrund und Ziel:Diese Studie untersucht die Präzision der virtuellen Simulation mit dem neuen Lasersystem Dorado CT4 bei 96 Patienten mit Prostatakarzinom.Patienten und Methodik:Die virtuelle Simulation (Abbildung 1) basierte bei 64 Patienten (Gruppe A) auf einem Spiral-CT mit 8 mm Schichtdicke und 8 mm Rekonstruktionsindex, bei 32 Patienten (Gruppe B) auf einem Spiral-CT mit 3 mm Schichtdicke und 3 mm Rekonstruktionsindex (Tabelle 1). Beide Gruppen wurden hinsichtlich der maximalen Differenz (Δmax) zwischen den Isozentren der virtuellen Simulation und den Isozentren der konventionellen Simulation verglichen.Ergebnisse:Im Gesamtkollektiv waren die mittleren Differenzen folgendermaßen: Δmax 5,7 ± 3,5 mm, Δx (links/rechts) 2,8 ± 2,9 mm, Δy (anterior/posterior) 4,5 ± 3,8 mm, Δz (kranial/kaudal) 2,1 ± 2,2 mm (Tabelle 2). In Gruppe A ergaben sich folgende Mittelwerte: Δmax 6,2 ± 3,8 mm, Δx 2,9 ± 3,1 mm, Δy 4,9 ± 4,2 mm, Δz 2,3 ± 2,3 mm. Die Mittelwerte in Gruppe B waren 4,8 ± 2,8 mm für Δmax, 2,7 ± 2,7 mm für Δx, 3,7 ± 2,7 mm für Δy und 1,7 ± 2,0 mm für Δz. Der Zeitpunkt der Strahlentherapie (primäre vs. Salvage-RT) und das RT-Regime (perkutane RT vs. High-Dose-Rate-Brachytherapie [HDR-BT] plus perkutane RT) hatten keinen signifikanten Einfluss auf Δmax (Tabelle 3).Schlussfolgerung:Die virtuelle Simulation mit dem Lasersystem Dorado CT4 bei der RT von Patienten mit Prostatakarzinom ist sehr präzise, und zwar unabhängig vom Zeitpunkt der RT (primäre RT, Salvage-RT) und vom RT-Regime (perkutane RT, HDR-BT plus perkutane RT). Schichtdicke und Rekonstruktionsindex des für die virtuelle Simulation verwendeten Planungs-CT sollten 3 mm betragen, um eine hohe Präzision zu erreichen.