A comprehensive quality assurance protocol for electromagnetic tracking in brachytherapy.

BACKGROUND: Electromagnetic tracking (EMT) systems have proven to be a valuable source of information regarding the location and geometry of applicators in patients undergoing brachytherapy (BT). As an important element of an enhanced and individualized pre-treatment verification, EMT can play a pivotal role in detecting treatment errors and uncertainties to increase patient safety. PURPOSE: The purpose of this study is two-fold: to design, develop and test a dedicated measurement protocol for the use of EMT-enabled afterloaders in BT and to collect and compare the data acquired from three different radiation oncology centers in different clinical environments. METHODS: A novel quality assurance (QA) phantom composed of a scaffold with supports to fix the field generator, different BT applicators, and reference sensors (sensor verification tools) was used to assess the precision (jitter error) and accuracy (relative distance errors and target registration error) of the EMT sensor integrated into an afterloader prototype. Measurements were repeated in different environments where EMT measurements are likely to be performed, namely an electromagnetically clean laboratory, a BT suite, an operating room, and, if available, a CT suite and an MRI suite dedicated to BT. RESULTS: The mean positional jitter was consistently under 0.1 mm across all measurement points, with a slight trend of increased jitter at greater distances from the field generator. The mean variability of sensor positioning in the tested tandem and ring gynecological applicator was also below 0.1 mm. The tracking accuracy close to the center of the measurement volume was higher than at its edges. The relative distance error at the center was 0.2-0.3 mm with maximum values reaching 1.2-1.8 mm, but up to 5.5 mm for measurement points close to the edges. In general, similar accuracy results were obtained in the clinical environments and in all investigated institutions (median distance error 0.1-0.4 mm, maximum error 1.0-2.0 mm), however, errors were found to be larger in the CT suite (median distance error up to 1.0 mm, maximum error up to 3.6 mm). CONCLUSION: The presented quality assessment protocol for EMT systems in BT has demonstrated that EMT offers a high-accuracy determination of the applicator/implant geometry even in clinical environments. In addition to that, it has provided valuable insights into the performance of EMT-enabled afterloaders across different radiation oncology centers.

Accuracy of an electromagnetic tracking enabled afterloader based on the automated registration with CT phantom images.

BACKGROUND: Electromagnetic tracking (EMT) has been researched for brachytherapy applications, showing a great potential for automating implant reconstruction, and overcoming image-based limitations such as contrast and spatial resolution. One of the challenges of this technology is that it does not intrinsically share the same reference frame as the patient's medical imaging. PURPOSE: To present a novel phantom that can be used for a comprehensive quality assurance (QA) program of brachytherapy EMT systems and use this phantom to validate a novel applicator-based registration method of EMT and image reference frames for gynecological (GYN) interstitial brachytherapy. MATERIALS AND METHODS: Eleven 6F-catheters (20 cm long), one 6F round tip catheter (29.4 cm long) and a tandem and ring gynecological applicator (Elekta, CT/MR 60°, 40 mm long tandem, 30 mm diameter ring) were placed in a rigid custom-made phantom (Elekta Brachytherapy, Veenendaal, The Netherlands) to reconstruct their geometry using a five-degree of freedom EMT sensor attached to an afterloader's check cable. All EMT reconstructions were done in three different environments: disturbance free (no metal nearby), computed tomography (CT)-on-rails brachytherapy suite and magnetic resonance imaging (MRI) brachytherapy suite. Implants were placed parallel to a magnetic field generatorand were reconstructed using two different acquisition methods: step-and-record and continuous motion. In all cases, the acquisition is performed at a rate of approximately 40 Hz. A CT scan of the phantom inside a water cube was obtained. In the treatment planning system (TPS), all catheters in the CT images were manually reconstructed and the applicator reconstruction was achieved by manually placing its solid 3D model, found in the applicator library of the TPS. The Iterative Closest Point and the Coherent Point Drift algorithms were used, initialized with four known points, to register both EMT and CT scan reference frames using corresponding points from the EMT and CT based reconstructions of the phantom, following three approaches: one gynecological applicator, four interstitial catheters inside four calibration plates having an S-shaped path, and four 5 mm diameter ceramic marbles found in each of the four calibration plates. Once registered, the registration error (perpendicular distance) was computed. RESULTS: The absolute median deviation from the expected value for EMT measurements in the disturbance free environment, CT-on-rails brachytherapy suite, and MRI-brachytherapy suite are 0.41, 0.23, and 0.31 mm, respectively, while for the CT scan it is 0.18 mm. These values significantly lie below the sensor's expected accuracy of 0.70 mm (p < 0.001), suggesting that the environment did not have a significant impact on the measurements, given that care is taken in the immediate surroundings. In all three environments, the two acquisitions and three registration approaches have mean and median registration errors that lie at or below 1 mm, which is lower than the clinical acceptable threshold of 2 mm. CONCLUSIONS: The novel phantom allowed to successfully evaluate the accuracy of EMT-based reconstructions of catheters and a GYN tandem and ring applicator in different clinical environments. A registration method based only on the applicator geometry, reconstructed withan EMT sensor and the TPS solid applicator library, was validated and shows clinically acceptable accuracy, comparable to CT-based reconstruction but within a few minutes. Since the applicator is also visible in MRI, this method could potentially be used in clinics in an EMT-MR interstitial GYN brachytherapy workflow.

Estimating follow-up CTs from geometric deformations of catheter implants in interstitial breast brachytherapy: A feasibility study using electromagnetic tracking.

BACKGROUND: Electromagnetic tracking (EMT) systems have been shown to provide valuable information on the geometry of catheter implants in breast cancer patients undergoing interstitial brachytherapy (iBT). In the context of an extended patient-specific, pre-treatment verification, EMT can play a key role in determining the potential need and, if applicable, the appropriate time for treatment adaptation. To detect dosimetric shortcomings the relative position between catheters, and target volume and critical structures must be known. Since EMT cannot provide the anatomical context and standard imaging techniques such as cone-beam CT are not yet available in most brachytherapy suites, it is not possible to detect anatomic changes on a daily or fraction basis, so the need for adaptive planning cannot be identified. PURPOSE: The aim of this feasibility study is to develop and evaluate a technique capable of estimating follow-up CTs at any time based on the initial treatment planning CT (PCT) and surrogate information about changes of the implant geometry from an EMT system. METHODS: A deformation vector field is calculated from two different implant reconstructions acquired in treatment position through EMT, the first immediately after the PCT and the second at another time point during the course of treatment. The calculation is based on discrete displacement vectors of pairs of control and target points. These are extrapolated by means of different radial basis functions in order to cover the entire CT volume. The adequate parameters for the calculation of the deformation field were identified. By warping the PCT according to the deformation field, one obtains an estimated CT (ECT) that reflects the geometric changes. For the proof of concept, ECTs were computed for the time point of the clinical follow-up CT (FCT) that is embedded in the treatment workflow after the fourth fraction. RESULTS: ECT and clinical FCTs of 20 patients were compared to each other quantitatively in terms of absolute Hounsfield unit differences in the planning target volume (PTV) and in a convex hull (CH) enclosing the catheters. The median differences were 31.2  and 29.5 HU for the CH and the PTV, respectively. CONCLUSION: The proposed ECT approach was able to approximate the "anatomy of the day" and therefore, in principle, allows a dosimetric appraisal of the treatment plan quality before each fraction. In this way, it can contribute to a more detailed patient-specific quality assurance in iBT of the breast and help to identify the timing for a potential treatment adaptation.

Localization of reference points in electromagnetic tracking data and their application for treatment error detection in interstitial breast brachytherapy.

BACKGROUND: Electromagnetic tracking (EMT) is a promising technology that holds great potential to advance patient-specific pre-treatment verification in interstitial brachytherapy (iBT). It allows easy determination of the implant geometry without line-of-sight restrictions and without dose exposure to the patient. What it cannot provide, however, is a link to anatomical landmarks, such as the exit points of catheters or needles on the skin surface. These landmarks are required for the registration of EMT data with other imaging modalities and for the detection of treatment errors such as incorrect indexer lengths, and catheter or needle shifts. PURPOSE: To develop an easily applicable method to detect reference points in the positional data of the trajectory of an EMT sensor, specifically the exit points of catheters in breast iBT, and to apply the approach to pre-treatment error detection. METHODS: Small metal objects were attached to catheter fixation buttons that rest against the breast surface to intentionally induce a local, spatially limited perturbation of the magnetic field on which the working principle of EMT relies. This perturbation can be sensed by the EMT sensor as it passes by, allowing it to localize the metal object and thus the catheter exit point. For the proof-of-concept, different small metal objects (magnets, washers, and bushes) and EMT sensor drive speeds were used to find the optimal parameters. The approach was then applied to treatment error detection and validated in-vitro on a phantom. Lastly, the in-vivo feasibility of the approach was tested on a patient cohort of four patients to assess the impact on the clinical workflow. RESULTS: All investigated metal objects were able to measurably perturb the magnetic field, which resulted in missing sensor readings, that is two data gaps, one for the sensor moving towards the tip end and one when retracting from there. The size of the resulting data gaps varied depending on the choice of gap points used for calculation of the gap size; it was found that the start points of the gaps in both directions showed the smallest variability. The median size of data gaps was ⩽8 mm for all tested materials and sensor drive speeds. The variability of the determined object position was ⩽0.5 mm at a speed of 1.0 cm/s and ⩽0.7 mm at 2.5 cm/s, with an increase up to 2.3 mm at 5.0 cm/s. The in-vitro validation of the error detection yielded a 100% detection rate for catheter shifts of ≥2.2 mm. All simulated wrong indexer lengths were correctly identified. The in-vivo feasibility assessment showed that the metal objects did not interfere with the routine clinical workflow. CONCLUSIONS: The developed approach was able to successfully detect reference points in EMT data, which can be used for registration to other imaging modalities, but also for treatment error detection. It can thus advance the automation of patient-specific, pre-treatment quality assurance in iBT.

Automating implant reconstruction in interstitial brachytherapy of the breast: A hybrid approach combining electromagnetic tracking and image segmentation.

BACKGROUND AND PURPOSE: To develop a method for automatic reconstruction of catheter implants in interstitial brachytherapy (iBT) of the breast by means of electromagnetic tracking (EMT) with the goal of making treatment planning as time-effective and accurate as possible. MATERIALS AND METHODS: The implant geometry of 64 patients was recorded using an afterloader prototype with EMT functionality immediately after the planning CT. EMT data were transferred to the CT image space by rigidly registering the catheter fixation buttons as landmarks. To further improve reconstruction accuracy, the EMT reconstruction points were used as starting points to define small regions of interest (ROI) in the CT image. Within these ROIs, the catheter track was segmented in the CT using image processing operations such as thresholding and blob detection, thus refining the reconstruction. The perpendicular distance between the refined EMT implant reconstruction points and the manually reconstructed catheters by an experienced treatment planner was calculated as a measure of their geometric agreement. RESULTS: Geometrically, the refined EMT based implant reconstruction shows excellent agreement with the manual reconstruction. The median distance across all patients is 0.25 mm and the 95th percentile is 1 mm. Refinement takes approximately 0.5 s per reconstruction point and typically does not exceed 3 min per implant at no user interaction. CONCLUSION: The refined EMT based implant reconstruction proved to be extremely accurate and fast compared to manual reconstruction. The presented procedure can in principle be easily transferred to clinical routine and therefore has enormous potential to provide significant time savings in iBT treatment planning whilst improving reconstruction accuracy.

Influence and compensation of patient motion in electromagnetic tracking based quality assurance in interstitial brachytherapy of the breast.

PURPOSE: Electromagnetic tracking (EMT) is a versatile and viable technique for various quality assurance (QA) tasks in interstitial brachytherapy (iBT). As the duration of EMT measurements in iBT is on the order of minutes, they can be strongly affected by patient motion, especially breathing, which gives rise to motion artefacts. Since the centrepiece of EMT-related QA in iBT is to assess the geometry of the iBT implant or applicator, the absence of adequate motion compensation techniques could impede the use of EMT for QA purposes. A common way to compensate for this is to reference the data to either external or internal reference sensors (ERS, IRS) which are fixated on the patient's body or inside the applicator and therefore move with the patient. The purpose of the presented study is to provide a quantitative and in-depth analysis on the use of reference sensors for motion compensation. METHODS: First, the need for adequate motion compensation is identified both qualitatively and quantitatively using a phantom subjected to simulated breathing motion. An evaluation routine is developed to assess the influence of motion compensation using reference sensors on the acquired EMT data. The evaluation metric is based on the observed displacement of the EMT sensor from its mean position while dwelling at a dwell position (DP) for a dwell time of 1 s. After that, the routine is applied to a cohort of 54 breast cancer patients treated with iBT, and the quality of an ERS based compensation approach is assessed. In a subgroup of four patients, an IRS is inserted into the iBT implant and IRS-based compensation is compared to the ERS-based approach. Moreover, a correlation analysis of the ERS and IRS approach is performed, also including respiratory signals derived from the trajectories of the different reference sensors. RESULTS: It was found that motion compensation with ERS effectively reduced the mean sensor displacement per DP to median values as low as 0.11 mm in both phantom and patient measurements, which is below the precision of the EMT system (0.48 mm). Compensation using the IRS yielded comparable results and was as good as compensation with ERS. The results obtained from both approaches showed a strong correlation. Also the respiratory signals calculated from the different reference sensors were well correlated in most cases. CONCLUSION: These results indicate that motion compensation with ERS can effectively remove motion artefacts in EMT data. While compensation with an IRS leads to comparable results, the IRS occupies one catheter whose geometry hence cannot be assessed. The use of ERS has proven to be both effective and practical in clinical routine.

Plectin ensures intestinal epithelial integrity and protects colon against colitis.

Plectin, a highly versatile cytolinker protein, provides tissues with mechanical stability through the integration of intermediate filaments (IFs) with cell junctions. Here, we hypothesize that plectin-controlled cytoarchitecture is a critical determinant of the intestinal barrier function and homeostasis. Mice lacking plectin in an intestinal epithelial cell (IEC; PleΔIEC) spontaneously developed colitis characterized by extensive detachment of IECs from the basement membrane (BM), increased intestinal permeability, and inflammatory lesions. Moreover, plectin expression was reduced in the colons of ulcerative colitis (UC) patients and negatively correlated with the severity of colitis. Mechanistically, plectin deficiency in IECs led to aberrant keratin filament (KF) network organization and the formation of dysfunctional hemidesmosomes (HDs) and intercellular junctions. In addition, the hemidesmosomal α6ß4 integrin (Itg) receptor showed attenuated association with KFs, and protein profiling revealed prominent downregulation of junctional constituents. Consistent with the effects of plectin loss in the intestinal epithelium, plectin-deficient IECs exhibited remarkably reduced mechanical stability and limited adhesion capacity in vitro. Feeding mice with a low-residue liquid diet that reduced mechanical stress and antibiotic treatment successfully mitigated epithelial damage in the PleΔIEC colon.

High-Force Magnetic Tweezers with Hysteresis-Free Force Feedback.

Magnetic tweezers based on a solenoid with an iron alloy core are widely used to apply large forces (∼100 nN) onto micron-sized (∼5 µm) superparamagnetic particles for mechanical manipulation or microrheological measurements at the cellular and molecular level. The precision of magnetic tweezers, however, is limited by the magnetic hysteresis of the core material, especially for time-varying force protocols. Here, we eliminate magnetic hysteresis by a feedback control of the magnetic induction, which we measure with a Hall sensor mounted to the distal end of the solenoid core. We find that the generated force depends on the induction according to a power-law relationship and on the bead-tip distance according to a stretched exponential relationship. Combined, they describe with only three parameters the induction-force-distance relationship, enabling accurate force calibration and force feedback. We apply our method to measure the force dependence of the viscoelastic and plastic properties of fibroblasts using a protocol with stepwise increasing and decreasing forces. We group the measured cells in a soft and a stiff cohort and find that softer cells show an increasing stiffness but decreasing plasticity with higher forces, indicating a pronounced stress stiffening of the cytoskeleton. By contrast, stiffer cells show no stress stiffening but an increasing plasticity with higher forces. These findings indicate profound differences between soft and stiff cells regarding their protection mechanisms against external mechanical stress. In summary, our method increases the precision, simplifies the handling, and extends the applicability of magnetic tweezers.