Clinical Hemorheology and Microcirculation - Volume Pre-press, issue Pre-press

Authors: Fu, Tiantian | Ding, Hong | Xu, Chen | Zhu, Yuli | Xue, Liyun | Lin, Feng

Article Type: Research Article

Abstract: BACKGROUND: Fibrolamellar hepatocellular carcinoma (FLHCC) is an unusual variant of hepatocellular carcinoma (HCC). Revealing the imaging features is important to the diagnosis of FLHCC. OBJECTIVE: The aim of this study was to investigate the imaging characteristics of FLHCCs. METHODS: This retrospective study included 29 patients with histopathologically proved FLHCC and 96 patients proved HCC. All patients underwent an ultrasound examination pre-operation. RESULTS: The average maximum diameters of the FLHCC and HCC lesions were 7.4±4.1 cm and 4.1±3.0 cm, respectively. On the ultrasound, 79.3% of the FLHCCs and 12.3% of the HCCs showed the internal hyperechoic area; …48.3% of the FLHCCs and 3.3% of the HCCs displayed a strip-like attenuation. Calcification was noted in 20.7% of the FLHCCs, while none in HCCs. On the contrast-enhanced ultrasound (CEUS), all FLHCC lesions and 87.7% of the HCCs displayed hyperenhancement in the arterial phase. An internal, unenhanced central scar appeared in all FLHCCs, while none in HCCs. CONCLUSIONS: The ultrasonographic features of FLHCC lesions indicate that they are relatively large masses showing the internal hyperechoic area or strip-like attenuation or calcification on the US and hypervascularity with an unenhanced central scar on the CEUS as compared with conventional HCC lesions. Show more

Keywords: Carcinoma, hepatocellular, contrast media, ultrasonography, diagnosis

DOI: 10.3233/CH-200896

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-12, 2020

Authors: Fokam, Danielle | Aali, Maral | Dickson, Kayle | Scott, Cassidy | Holbein, Bruce | Zhou, Juan | Lehmann, Christian

Article Type: Research Article

Abstract: BACKGROUND: Sepsis is the result of a dysregulated host immune response to an infection. An ideal therapy would target both, the underlying infection and the dysregulated immune response. DIBI, a novel iron-binding polymer, was specifically developed as an antimicrobial agent and has also demonstrated in vivo anti-inflammatory properties. OBJECTIVE: This study aimed to further investigate the effects of DIBI with and without the antibiotic imipenem (IMI) in colon ascendens stent peritonitis (CASP)-induced experimental sepsis. METHODS: Vehicle, DIBI and/or IMI were administered in C57BL/6 mice after CASP surgery. Intestinal leukocyte activation and capillary perfusion was evaluated …by intravital microscopy. Moreover, bacterial load in peritoneal lavage fluid and blood, and plasma cytokine levels were assessed. In a second series of experiments, surgery to repair the colon was performed at 5 hr and these mice were followed for long-term survival over 7 days. RESULTS: DIBI reduced leukocyte adhesion, improved capillary blood flow, and decreased key plasma cytokines levels. DIBI also improved survival of infected mice, and greatly improved IMI efficacy. Survivors treated with IMI and DIBI were found to be free of systemic infection. CONCLUSIONS: DIBI has promising potential for sepsis treatment including its use as a sole or an adjunct therapeutic with antibiotics. Show more

DOI: 10.3233/CH-209207

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-21, 2020

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

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. Pre-press, no. Pre-press, pp. 1-7, 2020

Authors: Feder, Anna-Lena | Pion, Eric | Troebs, Johannes | Lenze, Ulrich | Prantl, Lukas | Htwe, Maung Maung | 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. Pre-press, no. Pre-press, pp. 1-9, 2020

Authors: Troeltzsch, Daniel | Niehues, Stefan M. | Fluegge, Tabea V. | 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. Pre-press, no. Pre-press, pp. 1-7, 2020

Authors: Kammerer, S. | Stroszczynski, C. | Jung, E.M.

Article Type: Research Article

Abstract: PURPOSE: The aim of our pilot study is to consider if the new flow presentation of the V-flow allows an assessment of the valve morphology of the crosses with respect to an insufficiency. MATERIAL AND METHODS: We performed a total of 50 investigations in which we documented a complete valve closure at the so called “crosse” at the valve of the large saphenous vein, a delayed valve closure or an incomplete valve closure with consecutive insufficiency at the crosse. The valve function of the crosse is crucial for the development of varicosis. For our study we recorded age …and gender of the patients. One patient in the study was suffering from Covid19. For the examinations we used a 3–9 MHz probe and a high-end ultrasound device. The examination was performed in a lying position and under quiet conditions. Before examination we practiced inhalation and exhalation as well as “pressing” or coughing with the patients, which resulted in a physiological closure of the venous valves. To rule out thrombosis, we carried out compression sonography on the legs. During the examination we documented the B-scan, the Color-Coded Duplex Sonography, the HR-flow and the V-flow for 3 seconds at the estuary of the crosses and incorporated these parameters into our measurements. Via V-flow, vectors can be imaged by representing the flow of erythrocytes and visually indicate a possible insufficiency due to delayed or incomplete valve closure. RESULTS: 31 of 50 patients (age 19–81years) showed a complete valve closure of the crosses, while three patients suffered from thrombosis. In eight of the 50 study participants (age 45–79 years) a delayed valve closure could be diagnosed by V-flow within 1–2 seconds. None of them had a thrombosis, but six of them suffered from cancer. In eleven patients we derived an incomplete valve closure with insufficiency (age 51–88 years). With reflux it took >2 seconds to close the valve. The patient with Covid19 also showed an incomplete valve closure with insufficiency. At the same time this patient showed a Covid19-associated deep vein thrombosis. Eight additional patients also had a thrombosis. Six of them suffered from cancer. Overall, the results were best visualized by V-Flow. CONCLUSION: The crosse as a significant venous structure can be well investigated by V-flow with respect to hemodynamic changes and a resulted reflux. Also associated changes close to the valve can be visualized well. Show more

Keywords: Valve insufficiency, crosses, FKDS (color-coded duplex sonography), V-flow

DOI: 10.3233/CH-209205

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-12, 2020

Authors: Nie, Yan | Xu, Xun | Wang, Weiwei | Ma, Nan | Lendlein, Andreas

Article Type: Research Article

Abstract: BACKGROUND: Keratinocytes are exposed to a thermal gradient throughout epidermal layers in human skin depending on environmental temperatures. OBJECTIVE: Here, the effect of cyclic temperature changes (Δ T) on HaCaT cell behaviors was explored. METHODS: HaCaT cells were cultured at constant temperature (37°C or 25°C) or under Δ T conditions. The morphology, mechanics, cell cycle progression, proliferation, and lipid synthesis of HaCaT cells were determined. RESULTS: Δ T conditions led to the inhomogeneous arrangement of the cytoskeleton in HaCaT cells, which resulted in enlarged size, rounder shape, and increased stiffness. Accumulation in the G2/M …phase in the cell cycle, a decreased proliferation rate, and a delayed lipogenesis were detected in HaCaT cells cultured under Δ T conditions. CONCLUSIONS: Δ T conditions resulted in the re-arrangement of the cytoskeleton in HaCaT cells, which showed similarity to the temperature-induced disassemble and re-assemble of cytoskeletons in keratinocyte in vivo . The altered cytoskeleton arrangement resulted in the cell enlargement and stiffening, which reflected the changes in cellular functions. The application of oscillatory temperature in the in vitro culture of keratinocytes provides a way to gain more insights into the role of skin in response to environmental stimuli and maintaining its homeostasis in vivo . Show more

Keywords: Oscillatory temperature, HaCaT cells, mechanics, morphology, proliferation

DOI: 10.3233/CH-209208

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-11, 2020

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

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 were 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. Pre-press, no. Pre-press, pp. 1-6, 2020

Authors: Bitterer, Florian | Hornung, Matthias | Platz Batista da Silva, Natascha | Schlitt, Hans J. | Stroszczynski, Christian | Wege, Anja K. | Jung, Ernst-Michael

Article Type: Research Article

Abstract: OBJECTIVE: To investigate the diagnostic accuracy of high-resolution ultrasound (HRU) for the detection of hepatic metastases of breast cancer in a humanized tumour mouse (HTM) using clinical standard technology. In addition, the efficiency of standard contrast-enhanced ultrasound (CEUS) [microbubbles of sulphur hexafluoride] and CEUS using a novel VEGFR2-targeted contrast agent [BR55 ® ] was examined. METHODS: A total of 14 HTM were sonographically examined twice. In addition to a human immune system, the animals developed hepatic tumour lesions after intrahepatic injection of BT-474 breast cancer cells. Digital cine loops from the arterial phase (15–35 sec), the portal venous phase (35–90 sec) …and the late phase (3–15 min) of the entire liver were analysed. Data were correlated to histopathology. RESULTS: After 9 months, half of the mice (7/14) revealed the development of hepatic breast cancer metastases. The detection limit was 1 mm tumour diameter. In particular, the use of targeted contrast media reduced the needed tumour diameter and helped to precisely classify tumour tissue. In 93% (13/14), the findings of ultrasound could be approved by histological examination by the pathologist. CONCLUSIONS: This study in HTM demonstrated the high feasibility of tumour specific contrast media and standard HRU contrast agents to detect early liver metastases. Show more

Keywords: Abdomen, contrast-enhanced ultrasound (CEUS), BR55 ® , SonoVue ® , humanized tumour mice (HTM)

DOI: 10.3233/CH-200898

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-14, 2020

Authors: Romano Bruno, Raphael | Schemmelmann, Mara | Wollborn, Jakob | Kelm, Malte | Jung, Christian

Article Type: Research Article

Abstract: OBJECTIVE: Diagnostic and risk stratification in intensive and emergency medicine must be fast, accurate, and reliable. The assessment of sublingual microcirculation is a promising tool for this purpose. However, its value is limited because the measurement is time-consuming in unstable patients. This proof-of-concept validation study examines the non-inferiority of a reduced frame rate in image acquisition regarding quality, measurement results, and time. METHODS: This prospective observational study included healthy volunteers. Sublingual measurement of microcirculation was performed using a sidestream dark field camera (SDF, MicroVision Medical®). Video-quality was evaluated with a modified MIQS (microcirculation image quality score). AVA 4.3C …software calculated microcirculatory parameters. RESULTS: Thirty-one volunteers were included. There was no impact of the frame rate on the time needed by the software algorithm to measure one video was 4.5 + 0.5 Minutes for AVA 4.3C. 86 frames per video provided non inferior video quality (MIQS 1.8 + 0.7 for 86 frames versus MIQS 2.2 + 0.6 for 215 frames, p  <  0.05), equal results for all microcirculatory parameters, but did not result in an advantage in terms of speed. No complications occurred. CONCLUSION: Video captures with 86 frames offer equal video quality and results for consensus parameters compared to 215 frames. However, there was no advantage regarding the time needed for the overall measurement procedure. Show more

Keywords: Microcirculation, risk-stratification, SDF-imaging, point-of-care measurement

DOI: 10.3233/CH-209201

Citation: Clinical Hemorheology and Microcirculation, vol. Pre-press, no. Pre-press, pp. 1-11, 2020