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.

Epac1 links prostaglandin E2 to ß-catenin-dependent transcription during epithelial-to-mesenchymal transition.

In epithelial cells, ß-catenin is localized at cell-cell junctions where it stabilizes adherens junctions. When these junctions are disrupted, ß-catenin can translocate to the nucleus where it functions as a transcriptional cofactor. Recent research has indicated that PGE2 enhances the nuclear function of ß-catenin through cyclic AMP. Here, we aim to study the role of the cyclic AMP effector Epac in ß-catenin activation by PGE2 in non-small cell lung carcinoma cells. We show that PGE2 induces a down-regulation of E-cadherin, promotes cell migration and enhances ß-catenin translocation to the nucleus. This results in ß-catenin-dependent gene transcription. We also observed increased expression of Epac1. Inhibition of Epac1 activity using the CE3F4 compound or Epac1 siRNA abolished the effects of PGE2 on ß-catenin. Further, we observed that Epac1 and ß-catenin associate together. Expression of an Epac1 mutant with a deletion in the nuclear pore localization sequence prevents this association. Furthermore, the scaffold protein Ezrin was shown to be required to link Epac1 to ß-catenin. This study indicates a novel role for Epac1 in PGE2-induced EMT and subsequent activation of ß-catenin.