Alexander Hann

Interactive Volumetry Of Liver Ablation Zones.

Percutaneous radiofrequency ablation (RFA) is a minimally invasive technique that destroys cancer cells by heat. The heat results from focusing energy in the radiofrequency spectrum through a needle. Amongst others, this can enable the treatment of patients who are not eligible for an open surgery. However, the possibility of recurrent liver cancer due to incomplete ablation of the tumor makes post-interventional monitoring via regular follow-up scans mandatory. These scans have to be carefully inspected for any conspicuousness. Within this study, the RF ablation zones from twelve post-interventional CT acquisitions have been segmented semi-automatically to support the visual inspection. An interactive, graph-based contouring approach, which prefers spherically shaped regions, has been applied. For the quantitative and qualitative analysis of the algorithm’s results, manual slice-by-slice segmentations produced by clinical experts have been used as the gold standard (which have also been compared among each other). As evaluation metric for the statistical validation, the Dice Similarity Coefficient (DSC) has been calculated. The results show that the proposed tool provides lesion segmentation with sufficient accuracy much faster than manual segmentation. The visual feedback and interactivity make the proposed tool well suitable for the clinical workflow.

HTC Vive MeVisLab integration via OpenVR for medical applications

Virtual Reality, an immersive technology that replicates an environment via computer-simulated reality, gets a lot of attention in the entertainment industry. However, VR has also great potential in other areas, like the medical domain, Examples are intervention planning, training and simulation. This is especially of use in medical operations, where an aesthetic outcome is important, like for facial surgeries. Alas, importing medical data into Virtual Reality devices is not necessarily trivial, in particular, when a direct connection to a proprietary application is desired. Moreover, most researcher do not build their medical applications from scratch, but rather leverage platforms like MeVisLab, MITK, OsiriX or 3D Slicer. These platforms have in common that they use libraries like ITK and VTK, and provide a convenient graphical interface. However, ITK and VTK do not support Virtual Reality directly. In this study, the usage of a Virtual Reality device for medical data under the MeVisLab platform is presented. The OpenVR library is integrated into the MeVisLab platform, allowing a direct and uncomplicated usage of the head mounted display HTC Vive inside the MeVisLab platform. Medical data coming from other MeVisLab modules can directly be connected per drag-and-drop to the Virtual Reality module, rendering the data inside the HTC Vive for immersive virtual reality inspection.

Tuning IL-2 signaling by ADP-ribosylation of CD25

Control of immunologic tolerance and homeostasis rely on Foxp3+CD4+CD25+ regulatory T cells (Tregs) that constitutively express the high affinity receptor for Interleukin-2, CD25. Tregs proliferate in response to injections of IL-2/anti-IL-2 antibody complexes or low doses of IL-2. However, little is known about endogenous mechanisms that regulate the sensitivity of CD25 to signaling by IL-2. Here we demonstrate that CD25 is ADP-ribosylated at Arg35 in the IL-2 binding site by ecto-ADP-ribosyltransferase ARTC2.2, a toxin-related GPI-anchored ecto-enzyme. ADP-ribosylation inhibits binding of IL-2 by CD25, IL-2- induced phosphorylation of STAT5, and IL-2-dependent cell proliferation. Our study elucidates an as-yet-unrecognized mechanism to tune IL-2 signaling. This newly found mechanism might thwart Tregs at sites of inflammation and thereby permit a more potent response of activated effector T cells.

RFA-Cut: Semi-automatic Segmentation of Radiofrequency Ablation Zones with and without Needles via Optimal s-t-Cuts

In this contribution, we present a semi-automatic segmentation algorithm for radiofrequency ablation (RFA) zones via optimal s-t-cuts. Our interactive graph-based approach builds upon a polyhedron to construct the graph and was specifically designed for computed tomography (CT) acquisitions from patients that had RFA treatments of Hepatocellular Carcinomas (HCC). For evaluation, we used twelve post-interventional CT datasets from the clinical routine and as evaluation metric we utilized the Dice Similarity Coefficient (DSC), which is commonly accepted for judging computer aided medical segmentation tasks. Compared with pure manual slice-by-slice expert segmentations from interventional radiologists, we were able to achieve a DSC of about eighty percent, which is sufficient for our clinical needs. Moreover, our approach was able to handle images containing (DSC=75.9%) and not containing (78.1%) the RFA needles still in place. Additionally, we found no statistically significant difference (p<;0.423) between the segmentation results of the subgroups for a Mann-Whitney test. Finally, to the best of our knowledge, this is the first time a segmentation approach for CT scans including the RFA needles is reported and we show why another state-of-the-art segmentation method fails for these cases. Intraoperative scans including an RFA probe are very critical in the clinical practice and need a very careful segmentation and inspection to avoid under-treatment, which may result in tumor recurrence (up to 40%). If the decision can be made during the intervention, an additional ablation can be performed without removing the entire needle. This decreases the patient stress and associated risks and costs of a separate intervention at a later date. Ultimately, the segmented ablation zone containing the RFA needle can be used for a precise ablation simulation as the real needle position is known.

US-Cut: interactive algorithm for rapid detection and segmentation of liver tumors in ultrasound acquisitions

Ultrasound (US) is the most commonly used liver imaging modality worldwide. It plays an important role in follow-up of cancer patients with liver metastases. We present an interactive segmentation approach for liver tumors in US acquisitions. Due to the low image quality and the low contrast between the tumors and the surrounding tissue in US images, the segmentation is very challenging. Thus, the clinical practice still relies on manual measurement and outlining of the tumors in the US images. We target this problem by applying an interactive segmentation algorithm to the US data, allowing the user to get real-time feedback of the segmentation results. The algorithm has been developed and tested hand-in-hand by physicians and computer scientists to make sure a future practical usage in a clinical setting is feasible. To cover typical acquisitions from the clinical routine, the approach has been evaluated with dozens of datasets where the tumors are hyperechoic (brighter), hypoechoic (darker) or isoechoic (similar) in comparison to the surrounding liver tissue. Due to the interactive real-time behavior of the approach, it was possible even in difficult cases to find satisfying segmentations of the tumors within seconds and without parameter settings, and the average tumor deviation was only 1.4mm compared with manual measurements. However, the long term goal is to ease the volumetric acquisition of liver tumors in order to evaluate for treatment response. Additional aim is the registration of intraoperative US images via the interactive segmentations to the patients pre-interventional CT acquisitions.

Feasibility of alternating induction and maintenance chemotherapy in pancreatic cancer

Chemotherapy regimens for pancreatic ductal adenocarcinoma (PDAC) have changed since the introduction of FOLFIRINOX. Due to toxicity, dosage and number of applied cycles are limited. In analogy to chemotherapy strategies in colon cancer we used a scheme of induction, maintenance and re-induction therapy in PDAC to alleviate such toxicities and increase the number of applied cycles. Here we report first experiences with this approach. Data of all patients who received FOLFIRINOX for metastatic or locally advanced PDAC in our center using induction chemotherapy followed by maintenance therapy from 2011 until November 2016 was collected and analyzed retrospectively. Progression free survival was assessed starting induction therapy until progressive disease (PD) during maintenance or treatment pause (PFS1) and until progression during re-induction therapy (PFS2). 13 patients received induction therapy which was followed by maintenance therapy. Re-induction due to PD during therapy was applied in 11 patients. The median PFS1 was 10.6 months (95% CI; 6.7–14.4), PFS2 was 14.1 months (95% CI; 8.2–19.9) and overall survival was 18.3 months (95% CI; 14.8–21.8). The use of FOLFIRINOX as induction, followed by maintenance and re-induction therapy in case of PD is feasible in the treatment of PDAC and might lead to a prolonged PFS with less toxicity.

Fatal outcome due to CO2 emboli during direct cholangioscopy

In this manuscript, we present two patients with fatal CO2 emboli who underwent direct peroral video cholangioscopy (POC). Emboli due to insufflation of air during such a procedure have been previously described. Because of its high solubility in blood, the use of CO2, but not of air, is strictly recommended to reduce the incidence of emboli. However, based on these fatal experiences, we would strongly suggest to refrain from performing direct cholangioscopy with uncontrolled insufflation of gas, even if CO2 was used, as in the two presented cases. POC is a well-established technique for the diagnosis of bile duct alterations and the treatment of bile duct stones.1 The use of small calibre, transnasal, gastroscopes for direct visualisation of the common bile duct clearly improved the visualisation of bile duct pathologies and allow for obtaining targeted biopsies.2 Mild-to-moderate cholangitis represents the most common adverse event related to this procedure.3 But the most serious adverse events are emboli due to insufflation of air during the procedure. Different publications report fatal outcome of such events.4–7 Because of its high solubility in blood, the use of CO2, but not of air, is strictly recommended to reduce the incidence of such emboli.1 ,8 ,9 To our best knowledge, an embolism adverse event …

Integration of the HTC Vive into the medical platform MeVisLab

Virtual Reality (VR) is an immersive technology that replicates an environment via computer-simulated reality. VR gets a lot of attention in computer games but has also great potential in other areas, like the medical domain. Examples are planning, simulations and training of medical interventions, like for facial surgeries where an aesthetic outcome is important. However, importing medical data into VR devices is not trivial, especially when a direct connection and visualization from your own application is needed. Furthermore, most researcher don’t build their medical applications from scratch, rather they use platforms, like MeVisLab, Slicer or MITK. The platforms have in common that they integrate and build upon on libraries like ITK and VTK, further providing a more convenient graphical interface to them for the user. In this contribution, we demonstrate the usage of a VR device for medical data under MeVisLab. Therefore, we integrated the OpenVR library into MeVisLab as an own module. This enables the direct and uncomplicated usage of head mounted displays, like the HTC Vive under MeVisLab. Summarized, medical data from other MeVisLab modules can directly be connected per drag-and-drop to our VR module and will be rendered inside the HTC Vive for an immersive inspection.

Targeted deep sequencing of circulating tumor DNA in metastatic pancreatic cancer

Purpose Precision medicine in pancreatic ductal adenocarcinoma (PDAC) could be substantially supported by tools that allow to establish and monitor the molecular setup of the tumor. In particular, noninvasive approaches are desirable, but not validated. Characterization of circulating tumor DNA (ctDNA) may help to achieve this goal. Experimental Design Blood samples from patients with metastatic PDAC prior to and during palliative treatment were collected. ctDNA and corresponding tumor tissue were analyzed by targeted next generation sequencing and droplet digital PCR for the 7 most frequently mutated genes in PDAC (TP53, SMAD4, CDKN2A, KRAS, APC, ATM, and FBXW7). Findings were correlated with clinical and imaging data. Results A total of 20 patients (therapy naïve n = 11; pretreated n = 9) were included. All therapy naïve patients (n = 11/11) presented with detectable ctDNA at baseline. In pretreated patients, 3/7 (prior to 2nd line treatment) and 2/2 (prior to 3rd line chemotherapy) had detectable ctDNA. The combined mutational allele frequency (CMAF) of KRAS and TP53 was chosen to reflect the amount of ctDNA. The median CMAF level significantly decreased during treatment (P = 0.0027) and increased at progression (P = 0.0104). CA19-9 analyses did not show significant differences. In treatment naïve patients, the CMAF levels during therapy significantly correlated with progression-free survival (Spearman, r = −0.8609, P = 0.0013). Conclusions Monitoring of ctDNA and its changes during treatment may enable to adapt therapeutic strategies to the specific molecular changes present at a certain time during treatment of mPDAC.

Interactive Outlining of Pancreatic Cancer Liver Metastases in Ultrasound Images

Ultrasound (US) is the most commonly used liver imaging modality worldwide. Due to its low cost, it is increasingly used in the follow-up of cancer patients with metastases localized in the liver. In this contribution, we present the results of an interactive segmentation approach for liver metastases in US acquisitions. A (semi-) automatic segmentation is still very challenging because of the low image quality and the low contrast between the metastasis and the surrounding liver tissue. Thus, the state of the art in clinical practice is still manual measurement and outlining of the metastases in the US images. We tackle the problem by providing an interactive segmentation approach providing real-time feedback of the segmentation results. The approach has been evaluated with typical US acquisitions from the clinical routine, and the datasets consisted of pancreatic cancer metastases. Even for difficult cases, satisfying segmentations results could be achieved because of the interactive real-time behavior of the approach. In total, 40 clinical images have been evaluated with our method by comparing the results against manual ground truth segmentations. This evaluation yielded to an average Dice Score of 85% and an average Hausdorff Distance of 13 pixels.