Randomized clinical trial of elective resection versus observation in diverticulitis with extraluminal air or abscess initially managed conservatively.

BACKGROUND: The aim of this RCT was to determine whether elective resection following successful non-operative management of a first episode of acute sigmoid diverticulitis complicated by extraluminal air with or without abscess is superior to observation in terms of recurrence rates. METHODS: This was a single-centre, sequential design RCT. Patients were randomized to elective surgery or observation following non-operative management and colonoscopy. Non-operative management included nil by mouth, intravenous fluids, intravenous antibiotics, CT with intravenous contrast on arrival at hospital, and repeat CT with intravenous and rectal contrast on day 3 in hospital. The primary endpoint was recurrent diverticulitis at 24 months. Patients with a history of sigmoid diverticulitis, immunosuppression or peritonitis were not included. RESULTS: Of 137 screened patients, 107 were assigned randomly to elective surgery (26) or observation (81), and underwent the allocated intervention after successful non-operative management. Conservative management failed in 15 patients. Groups were similar in age, sex, BMI, co-morbidities and colorectal POSSUM. Rates of recurrent diverticulitis differed significantly in the elective surgery and observation groups (8 versus 32 per cent; P = 0·019) at a mean(s.d.) follow-up of 37·8(8·6) and 35·2(9·2) months respectively. There was also a significant difference in time to recurrence (median 11 versus 7 months; P = 0·015). A total of 28 patients presented with recurrent diverticulitis complicated by extraluminal air and/or abscess (2 elective surgery, 26 observation), all of whom recovered with repeat non-operative management. CONCLUSION: The majority of patients observed following conservative management of diverticulitis with local extraluminal air do not require elective surgery. Registration number: NCT01986686 (http://www.clinicaltrials.gov).

Comprehensive patient-specific information preprocessing for cardiac surgery simulations.

PURPOSE: Patient-specific biomechanical simulations of the behavior of soft tissue gain importance in current surgery assistance systems as they can provide surgeons with valuable ancillary information for diagnosis and therapy. In this work, we aim at supporting minimally invasive mitral valve reconstruction (MVR) surgery by providing scenario setups for FEM-based soft tissue simulations, which simulate the behavior of the patient-individual mitral valve subject to natural forces during the cardiac cycle after an MVR. However, due to the complexity of these simulations and of their underlying mathematical models, it is difficult for non-engineers to sufficiently understand and adequately interpret all relevant modeling and simulation aspects. In particular, it is challenging to set up such simulations in automated preprocessing workflows such that they are both patient-specific and still maximally comprehensive with respect to the model. METHODS: In this paper, we address this issue and present a fully automated chain of preprocessing operators for setting up comprehensive, patient-specific biomechanical models on the basis of patient-individual medical data. These models are suitable for FEM-based MVR surgery simulation. The preprocessing methods are integrated into the framework of the Medical Simulation Markup Language and allow for automated information processing in a data-driven pipeline. RESULTS: We constructed a workflow for holistic, patient-individual information preprocessing for MVR surgery simulations. In particular, we show how simulation preprocessing can be both fully automated and still patient-specific, when using a series of dedicated MVR data analytics operators. The outcome of our operator chain is visualized in order to help the surgeon understand the model setup. CONCLUSION: With this work, we expect to improve the usability of simulation-based MVR surgery assistance, through allowing for fully automated, patient-specific simulation setups. Combined visualization of the biomechanical model setup and of the corresponding surgery simulation results fosters the understandability and transparency of our assistance environment.

Interventional real-time ultrasound imaging with an integrated electromagnetic field generator.

PURPOSE: Ultrasound (US) guided procedures are frequently performed for diagnosis and treatment of many diseases. However, there are safety and procedure duration limitations in US-guided interventions due to poor image quality and inadequate visibility of medical instruments in the field of view. To address this issue, we propose an interventional imaging system based on a mobile electromagnetic (EM) field generator (FG) attached to a US probe. METHODS: A standard US probe was integrated with an EM FG to allow combined movement of the FG with real-time imaging to achieve (1) increased tracking accuracy for medical instruments are located near the center of the tracking volume, (2) increased robustness because the FG is distant to large metallic objects, and (3) reduced setup complexity since time-consuming placement of the FG is not required. The new integrated US-FG imaging system was evaluated by assessing tracking and calibration accuracy in a clinical setting. To demonstrate clinical applicability, the prototype US-EMFG probe was tested in needle puncture procedures. RESULTS: The mobile EMFG attached to a US probe yielded sub-millimeter tracking accuracy despite the presence of metal close to the FG. Calibration errors were in the range of 1-2 mm. In an initial phantom study on US-guided needle punctures, targeting errors of about 3 mm were achieved. CONCLUSION: A combined US-EMFG probe is feasible and effective for tracking medical instruments relative to US images with high accuracy and robustness while keeping hardware complexity low.

MITK-US: real-time ultrasound support within MITK.

PURPOSE: Intra-procedural acquisition of the patient anatomy is a key technique in the context of computer-assisted interventions (CAI). Ultrasound (US) offers major advantages as an interventional imaging modality because it is real time and low cost and does not expose the patient or physician to harmful radiation. To advance US-related research, the purpose of this paper was to develop and evaluate an open-source framework for US-based CAI applications. MATERIALS AND METHODS: We developed the open-source software module MITK-US for acquiring and processing US data as part of the well-known medical imaging interaction toolkit (MITK). To demonstrate its utility, we applied the module to implement a new concept for US-guided needle insertion. Performance of the US module was assessed by determining frame rate and latency for both a simple sample application and a more complex needle guidance system. RESULTS: MITK-US has successfully been used to implement both sample applications. Modern laptops achieve frame rates above 24 frames per second. Latency is measured to be approximately 250 ms or less. CONCLUSION: MITK-US can be considered a viable rapid prototyping environment for US-based CAI applications.

[Database supported electronic retrospective analyses in radiation oncology: establishing a workflow using the example of pancreatic cancer]. / Datenbankbasierte digitale retrospektive Auswertung von Patientenkollektiven in der Radioonkologie: Etablierung eines Workflows am Beispiel des Pankreaskarzinoms.

PURPOSE: Especially in the field of radiation oncology, handling a large variety of voluminous datasets from various information systems in different documentation styles efficiently is crucial for patient care and research. To date, conducting retrospective clinical analyses is rather difficult and time consuming. With the example of patients with pancreatic cancer treated with radio-chemotherapy, we performed a therapy evaluation by using an analysis system connected with a documentation system. MATERIALS AND METHODS: A total number of 783 patients have been documented into a professional, database-based documentation system. Information about radiation therapy, diagnostic images and dose distributions have been imported into the web-based system. RESULTS: For 36 patients with disease progression after neoadjuvant chemoradiation, we designed and established an analysis workflow. After an automatic registration of the radiation plans with the follow-up images, the recurrence volumes are segmented manually. Based on these volumes the DVH (dose volume histogram) statistic is calculated, followed by the determination of the dose applied to the region of recurrence. All results are saved in the database and included in statistical calculations. CONCLUSION: The main goal of using an automatic analysis tool is to reduce time and effort conducting clinical analyses, especially with large patient groups. We showed a first approach and use of some existing tools, however manual interaction is still necessary. Further steps need to be taken to enhance automation. Already, it has become apparent that the benefits of digital data management and analysis lie in the central storage of data and reusability of the results. Therefore, we intend to adapt the analysis system to other types of tumors in radiation oncology.

Electromagnetic tracking for US-guided interventions: standardized assessment of a new compact field generator.

PURPOSE: One of the main challenges related to electromagnetic tracking in the clinical setting is a placement of the field generator (FG) that optimizes the reliability and accuracy of sensor localization. Recently, a new mobile FG for the NDI Aurora(®) tracking system has been presented. This Compact FG is the first FG that can be attached directly to an ultrasound (US) probe. The purpose of this study was to assess the precision and accuracy of the Compact FG in the presence of nearby mounted US probes. MATERIALS AND METHODS: Six different US probes were mounted onto the Compact FG by means of a custom-designed mounting adapter. To assess precision and accuracy of the Compact FG, we employed a standardized assessment protocol. Utilizing a specifically manufactured plate, we measured positional data on three levels of distances from the FG as well as rotational data. RESULTS: While some probes had negligible influence on tracking accuracy two probes increased the mean distance error up to 1.5 mm compared with a reference measurement of 0.5 mm. The jitter error consistently stayed below 0.2 mm in all cases. The mean relative error in orientation was found to be smaller than 3°. CONCLUSION: Attachment of an US probe to the Compact FG does not have a critical influence on tracking accuracy in most cases. Clinical benefit of this promising mobile FG must be shown in future studies.

Whole-abdominal IMRT for advanced ovarian carcinoma: planning issues and feasibility.

INTRODUCTION: Despite enormous efforts to improve therapeutic strategies for patients with advanced ovarian carcinoma, outcome remains poor even with the advent cisplatinum-based chemotherapy regimen or taxanes with over 70% of patients developing local failure. Several trials were able to establish the potential benefit of adjuvant whole abdominal RT (WAI) though at the cost of sometimes marked side-effects. New technologies like IMRT have the potential of sparing normal tissues thus also potentially limiting treatment-related toxicity, hence a phase I trial was initiated to evaluate potential clinical benefit of WAI with IMRT. We intended to demonstrate that whole-abdominal IMRT is feasible and can be used in a routine clinical setting. METHODS: A water-equivalent phantom containing OARs was created simulating organ shape of the upper abdomen to investigate the necessary number of beams for the upper abdominal target irrespective of the number of segments and hence treatment times. We prescribed a total dose of 30 Gy in 1.5 Gy fractions to the median of the target. IMRT treatment plans for three patients with advanced ovarian cancer were created using 2 isocentres and between 12 and 14 beams while restricting the number of segments so as to restrict treatment times to less than 45 min. Dose to OARs such as kidneys and liver was strictly limited even below established maxima. RESULTS: In the phantom plans, no clear indication as to the optimum number of beams could be shown though there seems to be a slight trend toward a higher number of beams yielding better results. Examples demonstrating clinically inacceptable dose distributions for plans using only 9 beams. Acceptable treatment plans for real patients could be achieved using 12-14 beams and 2 isocentres. Treatment plans consisted of 264-286 segments resulting in an overall treatment time of approximately 37-45 min. Mean doses to the kidneys could be limited to 29.3% [23.1-33.2%] (right), and 26.8% [21-30.4%] (left). 50% of the liver received less than 72.4% [61-83%]. CONCLUSION: IMRT for whole abdominal irradiation in patients with advanced ovarian carcinoma is applicable and feasible though treatment planning is complex and time-consuming. There is a significant reduction of dose to critical organs by using IMRT while maintaining target volume coverage.

Detection of respiratory motion in fluoroscopic images for adaptive radiotherapy.

Respiratory motion limits the potential of modern high-precision radiotherapy techniques such as IMRT and particle therapy. Due to the uncertainty of tumour localization, the ability of achieving dose conformation often cannot be exploited sufficiently, especially in the case of lung tumours. Various methods have been proposed to track the position of tumours using external signals, e.g. with the help of a respiratory belt or by observing external markers. Retrospectively gated time-resolved x-ray computed tomography (4D CT) studies prior to therapy can be used to register the external signals with the tumour motion. However, during treatment the actual motion of internal structures may be different. Direct control of tissue motion by online imaging during treatment promises more precise information. On the other hand, it is more complex, since a larger amount of data must be processed in order to determine the motion. Three major questions arise from this issue. Firstly, can the motion that has occurred be precisely determined in the images? Secondly, how large must, respectively how small can, the observed region be chosen to get a reliable signal? Finally, is it possible to predict the proximate tumour location within sufficiently short acquisition times to make this information available for gating irradiation? Based on multiple studies on a porcine lung phantom, we have tried to examine these questions carefully. We found a basic characteristic of the breathing cycle in images using the image similarity method normalized mutual information. Moreover, we examined the performance of the calculations and proposed an image-based gating technique. In this paper, we present the results and validation performed with a real patient data set. This allows for the conclusion that it is possible to build up a gating system based on image data, solely, or (at least in avoidance of an exceeding exposure dose) to verify gates proposed by the various external systems.

Kilovoltage CT using a linac-CT scanner combination.

Modern radiotherapy techniques such as intensity modulation are capable of generating complex dose distributions whose high dose areas tightly conform to the tumour target volume, sparing critical organs even when they are located in close proximity. This potential can only be exploited to its full extent when the accumulated dose actually delivered over the complete treatment course is sufficiently close to the dose computed on the initial CT scan used for treatment planning. Exact patient repositioning is mandatory, but also other sources of error, e.g. changes of the patient's anatomy under therapy, should be taken into account. At the German Cancer Research Center, we use a combination of a linear accelerator and a CT scanner installed in one room and sharing the same couch. It allows the quantification and correction of interfractional variations between planning and treatment delivery. In this paper, we describe treatments of prostate, paraspinal and head and neck tumours. All patients were immobilized by customized fixation devices and treated in a stereotactic setup. For each patient, frequent CT scans were taken during the treatment course. Each scan was compared with the original planning CT using manual checks and automatic rigid matching algorithms. Depending on the individual case, the adaptation to variations was carried out offline after several fractions or in real-time between the CT scan and linac irradiation. We discuss the techniques for detecting and correcting interfractional errors and outline the procedural steps of a linac-CT scanner-supported radiation treatment course.

An enhanced block matching algorithm for fast elastic registration in adaptive radiotherapy.

Image registration has many medical applications in diagnosis, therapy planning and therapy. Especially for time-adaptive radiotherapy, an efficient and accurate elastic registration of images acquired for treatment planning, and at the time of the actual treatment, is highly desirable. Therefore, we developed a fully automatic and fast block matching algorithm which identifies a set of anatomical landmarks in a 3D CT dataset and relocates them in another CT dataset by maximization of local correlation coefficients in the frequency domain. To transform the complete dataset, a smooth interpolation between the landmarks is calculated by modified thin-plate splines with local impact. The concept of the algorithm allows separate processing of image discontinuities like temporally changing air cavities in the intestinal track or rectum. The result is a fully transformed 3D planning dataset (planning CT as well as delineations of tumour and organs at risk) to a verification CT, allowing evaluation and, if necessary, changes of the treatment plan based on the current patient anatomy without time-consuming manual re-contouring. Typically the total calculation time is less than 5 min, which allows the use of the registration tool between acquiring the verification images and delivering the dose fraction for online corrections. We present verifications of the algorithm for five different patient datasets with different tumour locations (prostate, paraspinal and head-and-neck) by comparing the results with manually selected landmarks, visual assessment and consistency testing. It turns out that the mean error of the registration is better than the voxel resolution (2 x 2 x 3 mm(3)). In conclusion, we present an algorithm for fully automatic elastic image registration that is precise and fast enough for online corrections in an adaptive fractionated radiation treatment course.

An optimized workflow for the integration of biological information into radiotherapy planning: experiences with T1w DCE-MRI.

Planning of radiotherapy is often difficult due to restrictions on morphological images. New imaging techniques enable the integration of biological information into treatment planning and help to improve the detection of vital and aggressive tumour areas. This might improve clinical outcome. However, nowadays morphological data sets are still the gold standard in the planning of radiotherapy. In this paper, we introduce an in-house software platform enabling us to combine images from different imaging modalities yielding biological and morphological information in a workflow driven approach. This is demonstrated for the combination of morphological CT, MRI, functional DCE-MRI and PET data. Data of patients with a tumour of the prostate and with a meningioma were examined with DCE-MRI by applying pharmacokinetic two-compartment models for post-processing. The results were compared with the clinical plans for radiation therapy. Generated parameter maps give additional information about tumour spread, which can be incorporated in the definition of safety margins.

Real-time dose calculation and visualization for the proton therapy of ocular tumours.

A new real-time dose calculation and visualization was developed as part of the new 3D treatment planning tool OCTOPUS for proton therapy of ocular tumours within a national research project together with the Hahn-Meitner Institut Berlin. The implementation resolves the common separation between parameter definition, dose calculation and evaluation and allows a direct examination of the expected dose distribution while adjusting the treatment parameters. The new tool allows the therapist to move the desired dose distribution under visual control in 3D to the appropriate place. The visualization of the resulting dose distribution as a 3D surface model, on any 2D slice or on the surface of specified ocular structures is done automatically when adapting parameters during the planning process. In addition, approximate dose volume histograms may be calculated with little extra time. The dose distribution is calculated and visualized in 200 ms with an accuracy of 6% for the 3D isodose surfaces and 8% for other objects. This paper discusses the advantages and limitations of this new approach.

Technical aspects of internet-based knowledge presentation in radiotherapy.

Three-dimensional radiotherapy planning is a complex and time-consuming optimization process which requires much experience. To simplify and to speed up the process of treatment planning as well as to exchange experience and therapeutic knowledge, the department of Medical Physics at the German Cancer Research Centre (DKFZ) in Heidelberg is developing an Internet-based 3D Radiotherapy planning and Information System (IRIS). IRIS designed internet-based client-server application, implemented using Java, CORBA and PVM. The concept of IRIS combines the functionality of an interactive tutorial with a discussion forum, teleconferencing tool and an atlas of dose distributions. Furthermore an integral knowledge-based system provides automatically generated, preoptimized treatment plans. This paper explains the technical design of the system and gives an overview of experiences gained by the technical realization of a first prototype using currently available internet technology. The prototype is currently running for testing in the intranet of DKFZ.

Limitations for three-dimensional ultrasound imaging through a bore-hole trepanation.

The intraoperative shift of neuroanatomical landmarks that serve as reference points is an unsolved problem in current neuronavigation. Monitoring the position of these landmarks requires repeated intraoperative imaging. We analyzed the effectiveness of a 3-D ultrasound system for imaging through a bore-hole trepanation. A tissue-mimicking ultrasound phantom and plastic pads with bore-holes were utilized for in vitro tests of the system. Reducing the diameter of the simulated bore-hole decreased the image quality and reduced the field of view. The multiple plane mode of the 3-D ultrasound system allows reconstruction of images in arbitrary imaging planes on the basis of intraoperatively acquired 3-D datasets. Selecting planes that are coplanar with preoperative MRI scans, we were able to identify neuroanatomical landmarks in the reconstructed ultrasound images. Repeated 3-D ultrasound during a procedure might, therefore, allow recognition of a shift of these landmarks.

Inverse radiotherapy planning for a concave-convex PTV in cervical and upper mediastinal regions. Simulation of radiotherapy using an Alderson-RANDO phantom. Planning target volume.

AIM: Three-dimensional inverse treatment planning with modulated beams was applied for dosimetric optimization of a lengthy (22 cm) and complex (concave-convex) shaped planning target volume (PTV) in the cervical and upper mediastinal regions. MATERIAL AND METHOD: The planning was done for 9 coplanar beams spaced evenly at 40 intervals. Properties of 15 MV photons from a linear accelerator were simulated. The optimization of the fluence modulation profiles for each beam was based on a definition of the desired/permitted relative dose levels in the PTV and organs at risk, and a definition of the strengths of the constraints to achieve these objectives. RESULTS: An adequate dose delivery to the PTV and protection of the spinal cord are completely achievable. The dose delivered to the lungs is clinically acceptable with respect to the risk of radiation-induced pneumonitis. For reasons of physics, no further decrease in the radiation burden on the lungs can be attained with X-rays without compromising the PTV coverage. The radiation burden on some critical part of normal tissues was effectively reduced by application of a dummy organ at risk. CONCLUSION: The inverse planning is an effective method for conformal radiotherapy of large tumors as well. However, the power of the technique is insufficient when the tolerance dose of the neighbouring normal tissue is too low and its volume effect is high. Although requiring further operator interactions, introduction of dummy organs at risk may be of help in reducing the radiation burden on normal tissues.

[Image-guided therapy planning for interventional stereotactic therapy of brain tumors]. / Bildgestützte Therapieplanung für die interventionelle stereotaktische Therapie von Hirntumoren.

A treatment planning system for stereotactical neurosurgery has been developed. A modular system has been designed which is readily extendable. Different modalities of tomography (CT, MRI) can be correlated and presented simultaneously in transverse, frontal and sagittal reconstructions. The volumes of interest are segmented with respect to the different modalities, and the positions of the catheters are defined. The calculation of dose must be adapted to the physical requirements of the therapy and is designed as an independent process. The calculated data are shown in various presentations. The treatment planning system is applied to intratumoral chemotherapy. The drug is encapsulated in small carriers for prolonged release and injected via catheters directly into the tumor interstitium, bypassing the blood-brain barrier. The dose is calculated using the time-dependent, three-dimensional finite elements method. To achieve homogeneous temporal and spatial drug distribution it is necessary to use a great number of catheters due to the limited diffusion of drug, which is not practical in neurosurgery. Therefore this therapy concept is useful for small volumes only. Interstitial hyperthermia and brachytherapy, in contrast to intratumoral chemotherapy, show successful clinical results.

[Computerized procedures in 3-dimensional radiotherapy planning]. / Computerverfahren in der dreidimensionalen Strahlentherapieplanung.

UNLABELLED: The aim of 3D radiotherapy treatment planning is to match the dose as closely as possible to the target volume, thus avoiding side effects in healthy tissue and radiosensitive organs at risk. A virtual radiotherapy simulator designed for the definition of treatment parameters and the analysis of precalculated dose distributions enables iterative optimization of treatment plans. METHODS: VOXELPLAN is a software package for 3D radiotherapy treatment planning developed at the German Cancer Research Center; it consists of user interfaces for image segmentation, virtual therapy simulation, dose calculation, plan evaluation and patient documentation. It is written in C and FORTRAN and runs on VAXstation 4000, IBM RS/6000 and DEC ALPHA hardware. RESULTS: Since 1990 a pilot installation of VOXELPLAN has been applied in clinical routine at the Center and at the University Clinic for Radiology, Heidelberg. Treatment for more than 1500 patients has been planned and carried out using the system, proving its technical and organizational applicability. CONCLUSIONS: We expect better acceptance and further dissemination of the techniques described, conformation therapy as well as (after its technical realization) inverse planning, from continuous optimization of the planning process.