Clinical Hemorheology and Microcirculation - Volume 76, issue 2

Authors: Hiebl, B. | Krüger-Genge, A. | Jung, F.

Article Type: Editorial

DOI: 10.3233/CH-209200

Citation: Clinical Hemorheology and Microcirculation, vol. 76, no. 2, pp. 121-122, 2020

Authors: Troebs, Johannes | Asam, Claudia | Pion, Eric | Prantl, Lukas | Aung, Thiha | Haerteis, Silke

Article Type: Research Article

Abstract: BACKGROUND: The ability to evaluate tumor development within experimental oncology is of upmost importance. However, determining tumor volumes in 3D in vivo tumor models is challenging. The chick chorioallantoic membrane (CAM) model represents an optimized xenograft model that surpasses many disadvantages that are inherent to rodent models and provides the opportunity of real-time monitoring of tumor growth. OBJECTIVE: The objective of this study was to introduce a new method that enables monitoring of tumor growth within the CAM model throughout the course of the experiment. METHODS: Sarcoma cell lines and sarcoma primary tumors were grafted …onto the CAM of fertilized chicken eggs. A digital microscope (Keyence VHX-6000) was used for 3D volume monitoring before and after tumor excision and compared it to tumor weight. RESULTS: Accuracy of tumor volumes was validated through correlation with tumor weight. In and ex ovo tumor volumes correlated significantly with tumor weight values. CONCLUSIONS: The described method can be used to assess the effects of chemotherapeutic agents on the growth of tumors that have been grafted onto the CAM and further advance personalized cancer therapy. In summary, we established a promising protocol that enables in vivo real-time tracking of tumor growth in the CAM model using a digital microscope. Show more

Keywords: Chorioallantoic membrane (CAM), in vivo tumor model, tumor profiling, rhabdomyosarcoma, sarcoma, volume measurement, 3D volume

DOI: 10.3233/CH-209216

Citation: Clinical Hemorheology and Microcirculation, vol. 76, no. 2, pp. 123-131, 2020

Authors: Feder, Anna-Lena | Pion, Eric | Troebs, Johannes | Lenze, Ulrich | Prantl, Lukas | Htwe, Maung Mg | Phyo, Aung | Haerteis, Silke | Aung, Thiha

Article Type: Research Article

Abstract: BACKGROUND: Osteosarcomas are a rare, heterogeneous and malignant group of bone tumors that have a high potential for metastasis and aggressive growth patterns. Treatment of metastasized osteosarcoma is often insufficient and research is compromised by problems encountered when culturing cells or analyzing genetic alterations due to the high level of intratumoral and intertumoral heterogeneity. The chick chorioallantoic membrane (CAM) model, a 3D-in-vivo -tumor-model, could potentially facilitate the investigation of osteosarcoma heterogeneity at an individual and highly specified level. OBJECTIVE: Objective was to establish the grafting and transplantation of different primary osteosarcoma tissue parts onto several consecutive CAMs for …tumor profiling and investigation of osteosarcoma heterogeneity. METHODS: Various parts of primary osteosarcoma tissue were grafted onto CAMs and were transplanted onto another CAM for five to seven consecutive times, enabling further experimental analyzes. RESULTS: Primary osteosarcoma tissue parts exhibited satisfactory growth patterns and displayed angiogenic development on the CAM. It was possible to graft and transplant different tumor parts several times while the tissue viability was still high and tumor profiling was performed. CONCLUSIONS: Primary osteosarcoma tissue grew on several different CAMs for an extended time period and neovascularization of serial transplanted tumor parts was observed, improving the versatility of the 3D-in-vivo -tumor-model. Show more

Keywords: Osteosarcoma, sarcoma, cancer, tumor heterogeneity, intratumoral heterogeneity, CAM model, 3D-in-vivo-tumor-model

DOI: 10.3233/CH-209204

Citation: Clinical Hemorheology and Microcirculation, vol. 76, no. 2, pp. 133-141, 2020

Authors: Jung, E.M. | Wertheimer, T. | Putz, F.J. | Jung, F. | Kammerer, S. | Pregler, B. | Luerken, L. | Stroszczynski, C. | Beyer, L.

Article Type: Research Article

Abstract: AIM: To evaluate the use of dynamic contrast enhanced ultrasound (CEUS) with parametric color-coded imaging and time intensity curve analysis (TIC) for planning and follow-up after prostate arterial embolization (PAE). MATERIAL/METHOD: Before and after selective iliacal embolization by PAE with a follow up of 6 months 18 male patients (43–78 years, mean 63±3.5 years) with histopathological proven benign prostate hyperplasia were examined by one experienced examiner. A multifrequency high resolution probe (1–6 MHz) was used for transabdominal ultrasound and CEUS with bolus injections of 2.4 ml sulphur-hexafluoride microbubbles. Independent evaluation of color-coded parametric imaging before and after PAE by in …PACS stored DICOM loops from arterial phase (10–15 s) up to 1min were performed. Criteria for successful treatment were reduction of early arterial enhancement by changes of time to peak (TTP) and area under the curve (AUC) by measurements in 8 regions of interest (ROI) of 5 mm in diameter at the margin and in the center and changes from hyperenhancement in parametric imaging (perfusion evaluation of arterial enhancement over 15 s) from red and yellow to blue and green by partial infarctions. Reference imaging method was the contrast high resolution 3 tesla magnetic resonance tomography (MRI) using 3D vibe sequences before and after PAE and for the follow up after 3 and 6 months. RESULTS: PAE was technically and clinically successful in all 18 patients with less clinical symptoms and reduction of the gland volume. In all cases color-coded CEUS parametric imaging was able to evaluate partial infarction after embolization with changes from red and yellow to green and blue colors in the embolization areas. Relevant changes could be evaluated for TIC-analysis of CEUS with reduced arterial enhancement in the arterial phase and prolonged enhancement of up to 1 min with significant changes (p  = 0.0024). The area under the curve (AUC) decreased from 676±255.04 rU (160 rU–1049 rU) before PAE to 370.43±255.19 rU (45 rU–858 rU) after PAE. Time to peak (TTP) did not change significantly (p  = 0.6877); TTP before PAE was 25.82±9.04 s (12.3 s–42.5 s) and after PAE 24.43±9.10 s (12–39 s). Prostate volume decreased significantly (p  = 0.0045) from 86.93±34.98 ml (30–139 ml) before PAE to 50.57±26.26 ml (19–117 ml) after PAE. There were no major complications and, in most cases (14/18) a volume reduction of the benign prostate hyperplasia occurred. CONCLUSION: Performed by an experienced examiner CEUS with parametric imaging and TIC-analysis is highly useful to further establish prostatic artery embolization (PAE) as a successful minimal invasive treatment of benign prostatic hyperplasia. Show more

Keywords: Contrast enhanced ultrasound (CEUS), parametric imaging, time intensity curve analysis (TIC), prostate arterial embolization (PAE)

DOI: 10.3233/CH-209202

Citation: Clinical Hemorheology and Microcirculation, vol. 76, no. 2, pp. 143-153, 2020

Authors: Schwarze, V. | Marschner, C. | Völckers, W. | de Figueiredo, G. Negrão | Rübenthaler, J. | Clevert, D.-A.

Article Type: Research Article

Abstract: BACKGROUND: HCC is the most frequent primary liver cancer entity. Major risk factors comprise chronic HBC and HCV infections, ALD or NAFLD. Apart from the anamnesis, the clinical examination and serologic analysis, an essential part of the diagnostic HCC work-up is due to imaging findings from sonography, CT or MRI scans. HCC lesions feature a distinct vascularization pattern: hyperenhancement during early arterial and hypoenhancement/wash-out during portal venous or delayed phases. CEUS facilitates dynamic assessment of microperfusion patterns of suspicious liver lesions. PURPOSE: The purpose of the present retrospective single-center study was to determine the diagnostic value of CEUS …for assessing HCC by comparison with findings from MRI scans. MATERIALS AND METHODS: Between 2004-2018 292 patients with suspicious liver lesions underwent CEUS and MRI. All patients underwent native B-mode, Color Doppler and CEUS after given informed consent. The applied contrast agent was a second-generation blood pool agent (SonoVue ®, Bracco, Milan, Italy). Every CEUS examination was performed and interpreted by a single experienced radiologist (EFSUMB Level 3). RESULTS: CEUS was performed on all included patients without occurrence of any adverse effects. CEUS showed a sensitivity of 96%, a specificity of 91%, a PPV of 95% and a NPV of 94% for analyzing HCC in comparison with MRI as the diagnostic gold standard. CONCLUSION: With a distinguished safety profile CEUS shows a high diagnostic accuracy in assessing HCC compared to corresponding results from MRI scans. Show more

Keywords: Hepatocellular cancer, HCC, liver, CEUS, MRI

DOI: 10.3233/CH-209213

Citation: Clinical Hemorheology and Microcirculation, vol. 76, no. 2, pp. 155-160, 2020

Authors: Huf, V.I. | Wohlgemuth, W.A. | Uller, W. | Piehler, A.P. | Goessmann, H. | Stroszczynski, C. | Jung, E.M.

Article Type: Research Article

Abstract: INTRODUCTION: Percutaneous sclerotherapy is a well-established treatment option for venous malformations (VM). A recently established sclerosing agent is ethanol-gel. Aim of this study was to identify, if contrast-enhanced ultrasound (CEUS) with an integrated perfusion analysis allows for differentiation between untreated VM, healthy tissue, and with gelified ethanol treated malformation tissue. MATERIAL AND METHODS: In this institutional review board approved prospective study symptomatic VM patients underwent CEUS at exactly the same position before and after sclerotherapy with ethanol-gel. Two experienced sonographers performed all examinations after the bolus injection of microbubbles using a multi-frequency probe with 6 –9 MHz of …a high-end ultrasound machine. An integrated perfusion analysis was applied in the center of the VM and in healthy, surrounding tissue. For both regions peak enhancement (peak), time to peak (TTP), area under the curve (AUC), and mean transit time (MTT) were evaluated. Wilcoxon signed rank test was executed; p -values <0.05 were regarded statistically significant. RESULTS: In 23 patients including children (mean age 25.3 years, 19 females) before treatment all identified parameters were significantly higher in the VM center compared to healthy tissue (peak: p  < 0.01; TTP: p  < 0.01; AUC: p  < 0.01; MTT: p  < 0.01). Comparing the VM center before and after treatment, TTP (p  < 0.02) and MTT (p  < 0.01) reduced significantly after sclerotherapy. In surrounding tissue only peak changed after treatment in comparison to pre-treatment results (p  = 0.04). Comparing data in the VM center with surrounding tissue after sclerotherapy, results still differed significantly for peak (p  < 0.01), TTP (p  < 0.01), and AUC (p  < 0.01), but assimilated for MTT (p  = 0.07). CONCLUSION: All with CEUS identified parameters seem to be excellent tools for differentiating between VM and healthy tissue. TTP and MTT could distinguish between with ethanol-gel sclerotized VM portions and untreated malformation parts and thereby might assist the monitoring of sclerotherapy with ethanol-gel. Show more

Keywords: Contrast-enhanced ultrasound, perfusion analysis, venous malformation, sclerotherapy, ethanol-gel

DOI: 10.3233/CH-209215

Citation: Clinical Hemorheology and Microcirculation, vol. 76, no. 2, pp. 161-170, 2020

Authors: Troeltzsch, Daniel | Niehues, Stefan Markus | Fluegge, Tabea | Neckel, Norbert | Heiland, Max | Hamm, Bernd | Shnayien, Seyd

Article Type: Research Article

Abstract: BACKGROUND: Detecting local tumor recurrence from post-treatment changes in head and neck cancer (HNC) remains a challenge. Based on the hypothesis that post-therapeutically altered tissue is bradytroph, lower perfusion values are expected in perfusion CT (PCT) while higher perfusion values are expected in recurrent malignant tissue. OBJECTIVES: This prospective study investigates PCT for post-treatment recurrent HNC detection with a maximum slope algorithm. METHODS: A total of 80 patients who received PCT of the head and neck for post-therapy follow-up, of which 63 had no tumor recurrence and 17 presented a histopathologically confirmed recurrence were examined. Regions …of interest were placed in the location of the initial tumor, in reference ipsilateral nuchal muscle tissue and the corresponding internal carotid artery. Perfusion was calculated using a single-input maximum slope algorithm. RESULTS: With PCT, recurrent HNC can be differentiated from post-treatment tissue (p  < 0.05). It further allows delineating recurrent tumor tissue from benign nuchal tissue of reference (p  < 0.05). PCT data of patients with and without recurrent HNC are comparable as perfusion values of reference tissues in patients with and without HNC do not differ (p  > 0.05). CONCLUSIONS: PCT in combination with a commercially available maximum slope algorithm offers radiologists a reliable imaging tool to detect recurrent head and neck cancer within post-therapeutically altered tissue. Show more

Keywords: Head and neck cancer, perfusion computed tomography, tumor recurrence

DOI: 10.3233/CH-209209

Citation: Clinical Hemorheology and Microcirculation, vol. 76, no. 2, pp. 171-177, 2020

Authors: Rickert, Dorothee | Steinhart, Helmut | Lendlein, Andreas

Article Type: Research Article

Abstract: BACKGROUND: The pharyngeal reconstruction is a challenging aspect after pharyngeal tumor resection. The pharyngeal passage has to be restored to enable oral alimentation and speech rehabilitation. Several techniques like local transposition of skin, mucosa and/or muscle, regional flaps and free vascularized flaps have been developed to reconstruct pharyngeal defects following surgery, in order to restore function and aesthetics. The reconstruction of the pharynx by degradable, multifunctional polymeric materials would be a novel therapeutical option in head and neck surgery. MATERIALS AND METHODS: Samples of an ethylene-oxide sterilized polymer (diameter 10 mm, 200μ m thick) were implanted for the reconstruction …of a standardized defect of the gastric wall in rats in a prospective study. The stomach is a model for a “worst case” application site to test the stability of the implant material under extreme chemical, enzymatical, bacterial, and mechanical load. RESULTS: Fundamental parameters investigated in this animal model were a local tight closure between the polymer and surrounding tissues, histological findings of tissue regeneration and systemic responses to inflammation. A tight anastomosis between the polymer and the adjacent stomach wall was found in all animals after polymer implantation (n  = 42). Histologically, a regeneration with glandular epithelium was found in the polymer group. No differences in the systemic responses to inflammation were found between the polymer group (n  = 42) and the control group (n  = 21) with primary wound closure of the defect of the gastric wall. CONCLUSIONS: A sufficient stability of the polymeric material is a requirement for the pharyngeal reconstruction with implant materials. Show more

Keywords: Oncological head and neck surgery, pharyngocutaneous fistulae, multifunctional polymeric materials, reconstruction of pharyngeal defects, animal model

DOI: 10.3233/CH-209212

Citation: Clinical Hemorheology and Microcirculation, vol. 76, no. 2, pp. 179-189, 2020

Authors: Schwarze, V. | Marschner, C. | de Figueiredo, G. Negrão | Rübenthaler, J. | Clevert, D.-A.

Article Type: Research Article

Abstract: BACKGROUND: Popliteal artery aneurysms (PAA) are the most common peripheral artery aneurysms. Most common cause is arteriosclerosis. Acute thromboembolic limb ischemia and rupture of the PAA depict severe complications. Diagnostic tools for identifying PAAs are (Doppler) ultrasound, CT/MR angiography and DSA. PURPOSE: The aim of the present retrospective single-center study is to assess the application and safety of CEUS for assessing untreated and treated PAAs. MATERIALS AND METHODS: 13 patients were included in this study on whom CEUS was performed between 2007–2016. CEUS examinations were performed and interpreted by an experienced single radiologist (EFSUMB Level 3). …RESULTS: CEUS allowed for the detection of PAAs in all cases. CEUS allowed for detection of partial thrombosis of PAA in 7/8 of untreated patients, proper exclusion of PAA upon femoro-popliteal bypass in 3 patients, incomplete exclusion of PAA upon femoro-popliteal bypass in 1 patient and ruling out of in-stent stenosis in 1 patient. CONCLUSION: CEUS is a useful and safe tool for in real-time evaluation of PAAs in the pre-/post-treatment status. In addition to conventional (Doppler) ultrasound and as an alternative tool to more elaborate imaging modalities, CEUS might be integrated in the future diagnostic work-up and follow-up of PAA patients. Show more

Keywords: Popliteal arterial aneurysm, PAA, arteriosclerosis, ultrasound, CEUS

DOI: 10.3233/CH-209214

Citation: Clinical Hemorheology and Microcirculation, vol. 76, no. 2, pp. 191-197, 2020

Authors: Curio, Jonathan | Abulgasim, Kamal | Kasner, Mario | Rroku, Andi | Lauten, Alexander | Lendlein, Andreas | Landmesser, Ulf | Reinthaler, Markus

Article Type: Research Article

Abstract: BACKGROUND: Transesophageal echocardiography (TEE) as a guiding tool for edge-to-edge transcatheter tricuspid valve repair (EETVr) using MitraClip (Abbott Vascular, Santa Clara, USA) may not offer sufficient image quality in a significant proportion of patients. OBJECTIVES: Intracardiac echocardiography (ICE) as additional guiding tool in EETVr with the MitraClip device. METHODS: Appropriate angulations of the ICE catheter to visualize each commissure of the tricuspid valve were established in 3D printed heart models. In a single tertiary-care center ICE was used to support EETVr as additional guidance when TEE image quality was insufficient. Procedural safety and outcomes up to …30-days were compared between ICE/TEE and TEE only guided patients. RESULTS: In 6 of 11 patients (54.5%) undergoing EETVr with MitraClip TEE alone was unsatisfactory, necessitating additional ICE guidance. In 4 of these 6 patients ICE enabled a successful completion of the procedure. The steering maneuvers identified in the 3D models were well applicable in all patients, providing examples for potential future ICE implementation in EETVr. Under both TEE alone (n  = 5) and ICE (n  = 6) guidance the rate of procedural complications was 0%. According to vena contracta values at discharge significant TR reduction was achievable in the treated cohort (p  = 0.011). At 30-days follow-up one patient (ICE guided) died following global heart failure, not associated with the procedure itself. CONCLUSIONS: ICE guidance may offer an additional tool to guide EETVr with the MitraClip device in patients with poor TEE quality, as it enables successful results without impairing procedural safety. Show more

Keywords: Intracardiac ultrasound, tricuspid regurgitation, transcatheter tricuspid valve repair, edge-to-edge repair

DOI: 10.3233/CH-209211

Citation: Clinical Hemorheology and Microcirculation, vol. 76, no. 2, pp. 199-210, 2020