Andreas Spuler

Assessing the rupture probability of intracranial aneurysms (IAs) remains challenging. Therefore, hemodynamic simulations are increasingly applied toward supporting physicians during treatment planning. However, due to several assumptions, the clinical acceptance of these methods remains limited.

Geometric parameters have been proposed for prediction of cerebral aneurysm rupture risk. Predicting the rupture risk for incidentally detected unruptured aneurysms could help clinicians in their treatment decision. However, assessment of geometric parameters depends on several factors, including the spatial resolution of the imaging modality used and the chosen reconstruction procedure. The aim of this study was to investigate the uncertainty of a variety of previously proposed geometric parameters for rupture risk assessment, caused by variability of reconstruction procedures. 26 research groups provided segmentations and surface reconstructions of five cerebral aneurysms as part of the Multiple Aneurysms AnaTomy CHallenge (MATCH) 2018. 40 dimensional and non-dimensional geometric parameters, describing aneurysm size, neck size, and irregularity of aneurysm shape, were computed. The medians as well as the absolute and relative uncertainties of the parameters were calculated. Additionally, linear regression analysis was performed on the absolute uncertainties and the median parameter values. A large variability of relative uncertainties in the range between 3.9 and 179.8% was found. Linear regression analysis indicates that some parameters capture similar geometric aspects. The lowest uncertainties < 6% were found for the non-dimensional parameters isoperimetric ratio, convexity ratio, and ellipticity index. Uncertainty of 2D and 3D size parameters was significantly higher than uncertainty of 1D parameters. The most extreme uncertainties > 80% were found for some curvature parameters. Uncertainty analysis is essential on the road to clinical translation and use of rupture risk prediction models. Uncertainty quantification of geometric rupture risk parameters provided by this study may help support development of future rupture risk prediction models.

Advanced morphology analysis and image-based hemodynamic simulations are increasingly used to assess the rupture risk of intracranial aneurysms (IAs). However, the accuracy of those results strongly depends on the quality of the vessel wall segmentation.

Ganglioneuroma (GN) of the adult is a rare benign tumour originating from neural crest-derived cells. In most cases, GN is found in the mediastinum or retroperitoneum incidentally and may present with unspecific symptoms caused by space-occupying effects. The correct diagnosis of a retroperitoneal mass is still a challenge. Nevertheless, a preoperatively confirmed diagnosis of GN may support the concept of a less radical approach and may help to prevent unnecessary morbidity or loss of function. We report a case of a symptomatic retroperitoneal paravertebral GN in a 33-year-old woman. She has been referred with abdominal discomfort, lancinating pain in the right leg, headache and nausea. Magnetic resonance imaging revealed a solid paravertebral tumour adjacent to the psoas muscle. Computed tomography-guided core needle biopsy yielded the diagnosis of GN. The tumour was resected completely via a laparotomy. Immunohistopathological examinations confirmed a benign GN. Diagnostic studies and therapeutic interventions of retroperitoneal GN are discussed. In our case, a core needle biopsy preceding complete resection was helpful to prevent too extensive surgical approach.

Muscle satellite cells promote regeneration and could potentially improve gene delivery for treating muscular dystrophies. Human satellite cells are scarce; therefore, clinical investigation has been limited. We obtained muscle fiber fragments from skeletal muscle biopsy specimens from adult donors aged 20 to 80 years. Fiber fragments were manually dissected, cultured, and evaluated for expression of myogenesis regulator PAX7. PAX7⁺ satellite cells were activated and proliferated efficiently in culture. Independent of donor age, as few as 2 to 4 PAX7⁺ satellite cells gave rise to several thousand myoblasts. Transplantation of human muscle fiber fragments into irradiated muscle of immunodeficient mice resulted in robust engraftment, muscle regeneration, and proper homing of human PAX7⁺ satellite cells to the stem cell niche. Further, we determined that subjecting the human muscle fiber fragments to hypothermic treatment successfully enriches the cultures for PAX7⁺ cells and improves the efficacy of the transplantation and muscle regeneration. Finally, we successfully altered gene expression in cultured human PAX7⁺ satellite cells with Sleeping Beauty transposon–mediated nonviral gene transfer, highlighting the potential of this system for use in gene therapy. Together, these results demonstrate the ability to culture and manipulate a rare population of human tissue-specific stem cells and suggest that these PAX7⁺ satellite cells have potential to restore gene function in muscular dystrophies.

Coils and flow diverters or stents are devices successfully used to treat cerebral aneurysms. Treatment aims to reduce intra-aneurysmal flow, thereby separating the aneurysmal sac from the blood circulation. The focus and this manuscript combining literature review and our original research is an analysis of changes in aneurysmal hemodynamics caused by endovascular treatment devices. Knowledge of post-treatment hemodynamics is a path to successful long-term treatment. Summarizing findings on hemodynamic impact of treatment devices, we conclude: coiling and stenting do not affect post-treatment intra-aneurysmal pressure, but significantly alter aneurysmal hemodynamics through flow reduction and a change in flow structure. The impact of treatment devices on aneurysmal flow depends, however, on a set of parameters including device geometry, course of placement, parent vessel and aneurysm geometry.

Hunterian ligation affecting hemodynamics in vessels was proposed to avoid rebleeding in a case of a fenestrated basilar artery aneurysm after incomplete coil occlusion. We studied the hemodynamics in vitro to predict the hemodynamic changes near the aneurysm remnant caused by Hunterian ligation. A transparent model was fabricated based on three-dimensional rotational angiography imaging. Arteries were segmented and reconstructed. Pulsatile flow in the artery segments near the partially occluded (coiled) aneurysm was investigated by means of particle image velocimetry. The hemodynamic situation was investigated before and after Hunterian ligation of either the left or the right vertebral artery (LVA/RVA). Since post-ligation flow rate in the basilar artery was unknown, reduced and retained flow rates were simulated for both ligation options. Flow in the RVA and in the corresponding fenestra vessel is characterized by a vortex at the vertebrobasilar junction, whereas the LVA exhibits undisturbed laminar flow. Both options (RVA or LVA ligation) cause a significant flow reduction near the aneurysm remnant with a retained flow rate. The impact of RVA ligation is, however, significantly higher. This in vitro case study shows that flow reduction near the aneurysm remnant can be achieved by Hunterian ligation and that this effect depends largely on the selection of the ligated vessel. Thus the ability of the proposed in vitro pipe-line to improve hemodynamic impact of the proposed therapy was successfully proved.

Cyclin A1 regulates cell cycle activity and proliferation in somatic and germ-line cells. Its expression increases in G1/S phase and reaches a maximum in G2 and M phases. Altered cyclin A1 expression might contribute to clinical symptoms in facioscapulohumeral muscular dystrophy (FSHD). Muscle biopsies were taken from the Vastus lateralis muscle for cDNA microarray, RT-PCR, immunohistochemistry and Western blot analyses to assess RNA and protein expression of cyclin A1 in human muscle cell lines and muscle tissue. Muscle fibers diameter was calculated on cryosections to test for hypertrophy. cDNA microarray data showed specifically elevated cyclin A1 levels in FSHD vs. other muscular disorders such as caveolinopathy, dysferlinopathy, four and a half LIM domains protein 1 deficiency and healthy controls. Data could be confirmed with RT-PCR and Western blot analysis showing up-regulated cyclin A1 levels also at protein level. We found also clear signs of hypertrophy within the Vastus lateralis muscle in FSHD-1 patients. In most somatic human cell lines, cyclin A1 levels are low. Overexpression of cyclin A1 in FSHD indicates cell cycle dysregulation in FSHD and might contribute to clinical symptoms of this disease.

Background and Study Aims Image-based computational fluid dynamics (CFD) provides a means for analysis of biofluid mechanical parameters of cerebral aneurysms. This may enable patient-specific rupture risk analysis and facilitate treatment decisions. Application of different imaging methods may, however, alter the geometrical basis of these studies. The present study compares geometry and hemodynamics of an aneurysm phantom model acquired by means of magnetic resonance imaging (MRI), computed tomography (CT), and rotational angiography (3DRA). Materials and Methods The phantom model of a basilaris artery aneurysm was fabricated based on data generated by CT angiography. This model underwent imaging by means of CT, MRI, and 3DRA. We compared the geometrical reconstructions using the original dataset with those obtained from CT, MRI, and 3DRA. Similarly, CFD analyses were performed using the four reconstructions (3DRA, MRI, CT, and original dataset). Results MRI and the 3DRA-based reconstructions yield mean reconstruction errors of 0.097 mm and 0.1 mm, which are by a factor of 2.5 better than the CT reconstruction. The maximal error for the aneurysm radius (7.11 mm) measurement was found in the 3DRA reconstruction and was 3.8% (0.28 mm). A comparison of calculated time-averaged wall shear stress (WSS) shows good correlations for the entire surface and, separately, for the surface of the aneurysmal sack. The maximal error of 8% of the mean WSS calculation of the whole surface was found for the CT reconstruction. The calculations of the aneurysmal sack mean WSS from the MRI reconstruction were estimated to have a maximal error of 7%. Conclusion All three imaging techniques (CT, MRI, 3DRA) adequately reproduce aneurysm geometry and allow meaningful CFD analyses.