Clinical Hemorheology and Microcirculation - Volume 43, issue 1-2

Authors: Greis, Christian

Article Type: Research Article

Abstract: Ultrasound contrast agents contain tiny gas-filled microbubbles which on intravenous injection are transported like red blood cells by the bloodstream. They are distributed to the entire macro- and microvascular system without extravasation (blood-pool tracer). Contrast-specific ultrasound modalities allow selective imaging of these microbubble contrast agents in real time, with excellent separation from underlying tissue signals. The dynamic wash-in and wash-out of a contrast bolus allows the detection and quantitative assessment of vascular flow and parenchymal perfusion. On complete filling of vascular structures the microbubble distribution delineates the vascular lumen and depicts the vascular architecture, down to tiny branches within parenchymal …tissue. Mathematical models for bolus kinetics and flash/replenishment kinetics allow precise quantification of relative blood volume and blood flow, with high temporal and spatial resolution. Contrast-enhanced ultrasound examinations can be repeated at short intervals and performed at the bedside, making this diagnostic method convenient for guidance of interventions and therapy monitoring. Future applications include the use of microbubbles as target-specific molecular imaging agents and as delivery systems for local drug and gene therapies. Show more

Keywords: Ultrasound, microbubbles, perfusion, microcirculation, diagnosis, quantification

DOI: 10.3233/CH-2009-1216

Citation: Clinical Hemorheology and Microcirculation, vol. 43, no. 1-2, pp. 1-9, 2009

Authors: Geis, S. | Schreml, S. | Lamby, P. | Obed, A. | Jung, E.M. | Nerlich, M. | Babilas, P. | Szeimies, R.-M. | Prantl, L.

Article Type: Research Article

Abstract: Background: Free flap transplantation is used more and more frequently in order to cover extensive wound defects. The basic prerequisite for successful flap salvage after flap failure is a short time interval from failure until revision. For this reason many different flap monitoring systems have been tested over the last years. But none of them has made the way into clinical routine. Objective: The aim of this clinical study was to study whether luminescence lifetime imaging (LLI) is an adequate method to assess flap viability during the postoperative period. In previous experiments LLI was proven to be a precise …and non-invasive monitoring system for transcutaneous oxygen measurement. Methods: ptc O2 of 9 patients was detected during a postoperative period of 72 hours. In all cases the transplantation was performed by the same experienced surgeon. During the first 4 hours almost constant ptc O2 values were detected (53±0.7 mmHg). During the following time intervals ptc O2 values decreased and reached a more or less constant level after approximately 12 hours. The mean ptc O2 decreased from 53±0.7 mmHg to 39±1.0 mmHg. In one case an immediate decrease of ptc O2 below 10 mmHg was observed and a subsequently intervention was necessary to improve flap perfusion. Conclusion: In this clinical trial, perfusion dynamics after free flap transplantation as well as the detection of vascular complications were demonstrated using LLI. Based on these data, LLI seems to be a sensitive and adequate monitoring system for the evaluation of free flap viability. Show more

Keywords: Oxygen, free flaps, luminescence lifetime imaging

DOI: 10.3233/CH-2009-1217

Citation: Clinical Hemorheology and Microcirculation, vol. 43, no. 1-2, pp. 11-18, 2009

Authors: Jung, E.M. | Prantl, L. | Schreyer, A.G. | Schreyer, C.I. | Rennert, J. | Walter, M. | Jung, W. | Hoffstetter, P. | Herold, T. | Zorger, N. | Feuerbach, S. | Fellner, C.

Article Type: Research Article

Abstract: Purpose: Evaluation of post-surgery tissue perfusion of free flaps of the lower leg with contrast enhanced harmonic imaging (CHI), laser-induced indocyanine green (ICG) fluorescence angiography and magnetic resonance imaging (MRI). Materials and methods: 10 patients with free flaps of the lower limb were evaluated with CHI, ICG-fluorescence angiography and perfusion weighted MRI. Perfusion weighted MRI was performed after intravenous bolus injection of 25 ml Gd-DTPA. The ICG fluorescence was detected by a near-infrared-laser device (λem = 780 nm). Ultrasound was carried out by an experienced examiner with a linear probe after intravenous bolus injection of 2.4 ml SonoVue® …. For MRI time intensity curves as well as color-coded blood volume maps of the whole free flap were qualitatively evaluated. For CHI and ICG time intensity curves in selected regions of interest were analyzed. A score from 1–5 (1 = low, 5 = excellent) was used for analysis of perfusion images by three independent readers. Results: In 3 cases (radialis, parascapular and lateral thigh flap) CHI, MRI and ICG perfusion imaging showed an excellent (score 4–5) contrast enhancement of the cutaneous and subcutaneous part of the free flaps. In 2 cases of osteocutaneous flaps perfusion in central and distal parts of the free flaps was reduced (score 2). Correlation between CHI, MRI and ICG was 0.69–0.83 for the distal parts of the free flaps and 0.74–0.87 for the center of the flaps (Spearman test). Perfusion in the center of the free flaps was significantly different for MRI and ICG and also for MRI and CHI (p<0.05, Wilcoxon test). Conclusion: These first results introduce CHI and MRI perfusion imaging as a promising post-surgery monitoring in patients with free flaps. Show more

Keywords: Free flaps, tissue perfusion, contrast-enhanced ultrasound, MRI, ICG fluorescence angiography

DOI: 10.3233/CH-2009-1218

Citation: Clinical Hemorheology and Microcirculation, vol. 43, no. 1-2, pp. 19-33, 2009

Authors: Lamby, P. | Prantl, L. | Schreml, S. | Pfister, K. | Mueller, M.P. | Clevert, D.-A. | Jung, E.M.

Article Type: Research Article

Abstract: Introduction: High resolution ultrasound (US) techniques as implemented in the latest generation of US machines provide imminently better resolution compared to previous high resolution models. This improvement is based on advanced transducer technologies as well as updated post-processing procedures. Furthermore, matrix linear transducers providing frequencies from 6 to 15 MHz are now available. The aim of the study was the evaluation of these new techniques for the immediate postoperative investigation of microcirculation after free tissue transfer by supplemental use of Contrast-Enhanced Ultrasound Imaging (CEUS). Patients and methods: To this end, we investigated 12 patients who underwent free tissue transfer …in order to cover tissue defects in various body regions. We utilized the new GE Logiq E9 equipped with a linear 6–9 MHz and a matrix 6–15 MHz probe as well as the GE Logiq 9 with the previous version of the linear 6–9 MHz probe. Both machines provide the modalities of SRI® , Cross Beam® and THI® . The perfusion curves were quantitatively analyzed using digital cine sequences (Qontrast® , Bracco, Italy). Furthermore, two independent investigators evaluated the digitally recorded images with respect to the resolution of details based on a scale ranging from 0 to 5, and after application of 2.4 ml SonoVue® (Bracco, Italy), evaluated the image quality regarding the representation of tissue perfusion. Results: None of the free flaps showed clinical or laboratory signs of flap failure during the hospital stay. Several flaps showed typical perfusion patterns relating to the flap type. The combination of SRI® , Cross Beam® and THI® allows, in most cases, a more exact differentiation of tissue graft outlines and tissue composition, in particular the tissue texture, compared to the use of B-scan only. In addition, the high resolution matrix technology combined with the broader spectrum of 6–15 MHz considerably improves the representation of image details compared to multifrequency probes with 6–9 MHz. The use of updated post-processing procedures as well as new transducer technologies in CEUS also results in improved resolution and thus achieves a higher score compared to previous models. Conclusion: At present, these new US technologies combined with the updated 6–9 MHz probe provide the optimal assessment of perfusion in cutaneous, subcutaneous and deeper tissue layers. The additional use of new multifrequency 6–15 MHz matrix probes improves the resolution in the B-mode to an even higher degree. Show more

Keywords: Contrast-enhanced ultrasound, free flap, microcirculation, matrix technologies

DOI: 10.3233/CH-2009-1219

Citation: Clinical Hemorheology and Microcirculation, vol. 43, no. 1-2, pp. 35-49, 2009

Authors: Stephan, B. | Schenk, J.F. | Nemeh, A. | Pindur, G.

Article Type: Research Article

Abstract: Despite increasing advances in microvascular free tissue transfer, flap failures, most commonly resulting from thrombosis at the anastomotic vascular site, remain a significant concern. Although several experimental and clinical studies have been carried out, no consensus has been reached so far on the efficacy, dosage and timing of anticoagulant agents available for the prevention and treatment of thrombosis in microvascular surgery. Inhibition of fibrin formation and platelet function or the use of thrombolytic agents is a common approach in the antithrombotic management. However, some agents exhibit serious side effects and all of them carry the risk of bleedings. The current …literature on the use of antithrombotic agents, targeting at clinical trials in microvascular surgery, is therefore reviewed, to provide an informative basis for recommendations for an appropriate pharmacological approach. Show more

Keywords: Microvascular surgery, free flaps, thrombosis, anticoagulation

DOI: 10.3233/CH-2009-1220

Citation: Clinical Hemorheology and Microcirculation, vol. 43, no. 1-2, pp. 51-56, 2009

Authors: Jung, E.M. | Schreyer, A.G. | Schacherer, D. | Menzel, C. | Farkas, S. | Loss, M. | Feuerbach, S. | Zorger, N. | Fellner, C.

Article Type: Research Article

Abstract: Aim: Evaluation and characterization of the vascularisation and perfusion of liver tumors by means of image fusion of dynamic contrast-enhanced ultrasound (CEUS), multidetector-CT (MD-CT) or magnetic resonance imaging (MRI) with the ultrasound navigation technique. Material: For interventional planning a real-time image fusion involving CEUS (LOGIQ E9, GE) was performed in 20 patients (12 men, 8 women, age 43–69 years, median 54) with histologically confirmed malignant liver tumors (9 × hepatocellular carcinoma (HCC), 5 × metastases, 2 × hemangiomas, 1 × cholangiocellular carcinoma (CCC), 1 × lymphoma, 1 × neuroendocrine tumor, 1 × focal nodular hypoplasia (FNH)). In 17 patients …the real-time CEUS was fused with contrast-enhanced MD-CT and in three patients with contrast-enhanced MRI (Gd-DTPA and liver-specific contrast medium Resovist® ). All of the ultrasound examinations were performed by an experienced examiner with a multi-frequency probe (2–5 MHz, LOGIQ E9, GE); dynamic image sequences up to 3 minutes in true agent detection mode of contrast harmonic imaging (CHI) were documented. An evaluation of the tumor was performed by the characterization of the dynamics of the contrast medium and microperfusion with CEUS, fused with MD-CT or MRI. Results: In 18/20 cases there was an accurate agreement with respect to the segmental localization of the tumor lesion. In 2/20 cases the localization was comparable with the image fusion of CEUS and reference imaging (a total of at least 65 lesions: 3 × 1 lesion, 5 × 2 lesions, 8 × 3 lesions, 2 × 5 lesions, 1 × 8 lesions, 1 × at least 10 lesions (multifocal)). With image fusion a certain characterization was attained in 17/20 cases. In 3/20 cases (lymphoma after liver transplantation, multifocal CCC, metastases of a neuroendocrine tumor) the diagnosis was at first doubtful and had to be confirmed histologically. In patients with HCC an evaluation of the tumor perfusion was feasible in all 9 cases (8/9 after local trans-arterial chemoembolization (TACE), 1/9 after radio frequency ablation (RFA)). A tendency toward the identification of more lesions with image fusion of CEUS and CT than with contrast-enhanced CT alone could be recognized (p=0.059). Conclusion: Applying a new real-time fusion technique of MD-CT or MRI with CEUS new possibilities for the evaluation, intervention and monitoring of the therapy of liver lesions were made possible, since the method also comprised the dynamic microperfusion. Show more

Keywords: Real-time image fusion, contrast-enhanced ultrasound (CEUS), liver lesions, CT, MRI

DOI: 10.3233/CH-2009-1221

Citation: Clinical Hemorheology and Microcirculation, vol. 43, no. 1-2, pp. 57-69, 2009

Authors: Fellner, C. | Doenitz, C. | Finkenzeller, T. | Jung, E.M. | Rennert, J. | Schlaier, J.

Article Type: Research Article

Abstract: Geometric distortions and low spatial resolution are current limitations in functional magnetic resonance imaging (fMRI). The aim of this study was to evaluate if application of parallel imaging or significant reduction of voxel size in combination with a new 32-channel head array coil can reduce those drawbacks at 1.5 T for a simple hand motor task. Therefore, maximum t-values (tmax ) in different regions of activation, time-dependent signal-to-noise ratios (SNR(t)) as well as distortions within the precentral gyrus were evaluated. Comparing fMRI with and without parallel imaging in 17 healthy subjects revealed significantly reduced geometric distortions in anterior–posterior direction. Using …parallel imaging, tmax only showed a mild reduction (7–11%) although SNR(t) was significantly diminished (25%). In 7 healthy subjects high-resolution (2 × 2 × 2 mm3 ) fMRI was compared with standard fMRI (3 × 3 × 3 mm3 ) in a 32-channel coil and with high-resolution fMRI in a 12-channel coil. The new coil yielded a clear improvement for tmax (21–32%) and SNR(t) (51%) in comparison with the 12-channel coil. Geometric distortions were smaller due to the smaller voxel size. Therefore, the reduction in tmax (8–16%) and SNR(t) (52%) in the high-resolution experiment seems to be tolerable with this coil. In conclusion, parallel imaging is an alternative to reduce geometric distortions in fMRI at 1.5 T. Using a 32-channel coil, reduction of the voxel size might be the preferable way to improve spatial accuracy. Show more

Keywords: fMRI, BOLD, parallel imaging, spatial resolution, array coil

DOI: 10.3233/CH-2009-1222

Citation: Clinical Hemorheology and Microcirculation, vol. 43, no. 1-2, pp. 71-82, 2009

Authors: Clevert, D.-A. | Stickel, M. | Minaifar, N. | Löhe, F. | Graeb, C. | Jauch, K.W. | Reiser, M.

Article Type: Research Article

Abstract: Purpose: This study compared the efficacy of contrast-enhanced ultrasound (CEUS) using a second generation contrast medium versus CT or MRA in the assessment of vascular and biliary complications in postoperative follow-up of liver transplantation. Methods and materials: The study group consisted of 36 consecutive liver transplant recipients who underwent post-transplantation CEUS examination after developing ascites and/or unclear liver function tests. Real time CEUS was performed after a bolus injection of SonoVue® (1.6–2.4 ml, Bracco, Imaging Germany) followed by 10 ml of saline solution. Using contrast harmonic imaging (CHI) technique (Logiq 9, GE) with a 2.5–4-MHz transducer, a low …mechanical index was chosen to avoid early destruction of the microbubbles (MI 0.1–0.2). In order to confirm the results, the patients underwent contrast-enhanced MRI or CT. Results: Complications were identified in 16 of 36 patients (44.4%). Five transplants (14%) had hepatic artery thrombosis (n=2) or significant stenosis (n=3). Six transplants (16%) developed portal vein stenosis (n=4) or portal vein thrombosis (n=2). MRI or CT confirmed the findings of the CEUS in all 11 cases. Biliary stricture at the anastomotic site was detected in 5 patients. MR-CP confirmed the findings of all strictures. Conclusion: Due to advances in contrast-enhanced US, vascular and biliary complications in the postoperative period following liver transplantation can be reliably diagnosed non-invasively on the intensive care unit. CEUS shows vascular as well as biliary complications in the postoperative patient with a high degree of accuracy. Show more

Keywords: Liver transplantation, contrast-enhanced ultrasound

DOI: 10.3233/CH-2009-1223

Citation: Clinical Hemorheology and Microcirculation, vol. 43, no. 1-2, pp. 83-94, 2009

Authors: Clevert, D.-A. | Stock, K. | Klein, B. | Slotta-Huspenina, J. | Prantl, L. | Heemann, U. | Reiser, M.

Article Type: Research Article

Abstract: Purpose: It was the aim of our study to combine the findings of contrast-enhanced ultrasound and ARFI-imaging in the evaluation of renal masses in comparison to the histological findings. Materials and methods: Fifteen patients with unclear kidney lesions were analyzed. We used a high-end ultrasound machine (Siemens ACUSON S2000™, Siemens Healthcare, Erlangen, Germany) with a multifrequency curved array 4 MHz or linear 9 MHz transducer. Contrast-enhanced ultrasound (bolus injection 1.6–2.4 ml SonoVue® ) was carried out. We obtained fifteen ARFI measurements from each patient with at least five values for quantification. The ARFI-ROI (region of interest) was placed in …the ventral margin of the kidney tumor and the whole ROI was covered by the tumor. The “reference-ROI” was placed in the ventral kidney parenchyma of the patient at a distance of at least two centimeters from the tumor. All renal tumors were surgically resected. In cases of complex renal cysts or anatomic variations mimicking renal tumors (“pseudo-tumors”), constant results of ultrasound examinations and additional MRI or multiphase CT over 6 months were required. Results: Fifteen patients were included in the study and were examined using the diagnostic ultrasound tools of our study The kidney tumors of our patients had diameters ranging from 1.5 to 8 cm and were located at depths ranging from 2 to 5.5 cm. ARFI imaging was also performed in all patients. A field up to a depth of 10 cm could be visualized for diagnostic use. Performing ARFI quantification using Siemens Virtual Touch™ Tissue Quantification we obtained minimum and maximum tissue shear velocities ranging from 1.6 to 3.42 m/s. The reference tissue ROIs showed values from 1.31 to 4.4 m/s. 12 cases were accepted for surgical resection. The visualization of lesions with Virtual Touch™ Tissue Imaging confirmed the measurements of ARFI quantification and were able to depict the different areas of stiffness in the kidney tissue. No infiltration of kidney veins or vena cava was detected by contrast-enhanced ultrasound. Of the 12 cases two “complicated” renal cysts were examined, and both showed Bosniak-III findings. Conclusion: ARFI imaging improves visualization of unclear renal masses in comparison to fundamental B-scan and adds new information about the tissue stiffness in a less time-consuming and more reproducible way. CEUS with SonoVue® allows an early evaluation of renal masses or complex cysts. Show more

Keywords: Acoustic Radiation Force Impulse (ARFI), renal tumors, contrast-enhanced ultrasound

DOI: 10.3233/CH-2009-1224

Citation: Clinical Hemorheology and Microcirculation, vol. 43, no. 1-2, pp. 95-107, 2009

Authors: Zuber-Jerger, I. | Schacherer, D. | Woenckhaus, M. | Jung, E.M. | Schölmerich, J. | Klebl, F.

Article Type: Research Article

Abstract: Purpose: The use of contrast enhancers has widened the possibilities of sonographic imaging, and allows the differentiation of characteristic enhancement patterns leading to diagnosis in focal liver lesions. The aim of our study was to evaluate contrast ultrasound signs in diagnosing malignant liver lesions. Methods: 86 patients with 100 solid liver lesions were enrolled. A baseline gray-scale sonogram was obtained with a multifrequency 4 C convex array probe, followed by contrast-enhanced sonography with a low mechanical index (<0.2) over 300 seconds. Final diagnosis was confirmed by histology or in case of haemangioma by CT/NMR and quantitative contrast harmonic imaging …(CHI) with perfusion analysis (qontrast). Results: 55 malignant (6 HCC, 46 secondary malignant lesions – 3 of them lymphoma, 3 cholangiocarcinoma), and 45 benign lesions (8 FNH, 1 von Meyenburg complex, 1 granuloma, 3 adenoma, 21 hemangioma, 2 focal fat storage imbalances, 7 abscesses, one scar, and in one case normal liver) were found. 51/55 malignant (all but one filia and three HCC), but also 17/45 benign lesions showed hypoperfusion in the late phase. The ultrasound pattern in the arterial phase differed in malignant lesions: 22 lesions were initially hypervascular, 20 had rim enhancement and in 13 lesions there was a non-specific vascularisation. In all but one malignant lesion a diminishing of contrast agent in the late phase compared to the arterial phase with respect to the surrounding liver tissue was observed. Only three benign lesions with this later sign were falsely diagnosed as malignant: one adenoma, one epitheloid granuloma, and a scar. Quantitative perfusion pattern was analyzed exemplary. Diminishing of contrast agent in the late phase compared to the arterial phase with respect to the surrounding liver tissue as a sign for malignancy had a positive predictive value of 95%, a sensitivity of 98%, a negative predictive value of 98%, and a specificity of 93%. Conclusions: Diminishing of contrast agent in the late phase compared to the arterial phase with respect to the surrounding liver tissue is a helpful sign in contrast enhanced ultrasound to diagnose malignancies. Show more

Keywords: Contrast ultrasound, liver lesion, late phase

DOI: 10.3233/CH-2009-1225

Citation: Clinical Hemorheology and Microcirculation, vol. 43, no. 1-2, pp. 109-118, 2009

Authors: Pfister, K. | Rennert, J. | Uller, W. | Schnitzbauer, A.A. | Stehr, A. | Jung, W. | Hofstetter, P. | Zorger, N. | Kasprzak, P.M. | Jung, E.M.

Article Type: Research Article

Abstract: Objective: Is Contrast Harmonic Imaging (CHI) comparable to computed tomography angiography (CTA) scan in detecting and characterizing suspected endoleaks after endovascular abdominal aneurysm repair in a non-selected group including reintervention procedure and branched endografts in daily practice? Material/methods: In a prospective study computed tomography angiography (CTA) and contrast-enhanced ultrasound (CEUS) were performed in 30 consecutive patients (26 males, 4 females, mean age: 72 years, range: 38–87) with suspected endoleaks in follow-up (mean 13 months, range: 1–95) after endovascular abdominal aneurysm repair or procedure in dissection or penetrated ulcer of the aorta (25 infrarenal, 5 suprarenal stent grafts, mean aortic …diameter 56 mm, range: 27–98). CTA was supposed to be gold standard for determining the presence of endoleaks (multislice CT, collimation 16 × 0.75 mm, 100 ml of iodized contrast agent bolus). Ultrasonography used a multi-frequency probe (1–4 MHz) with the modalities of colour coded Doppler sonography (CCDS), power Doppler (PD) combined with contrast enhancement and the technique of contrast harmonic imaging (CHI) and low mechanical index (MI < 0.2). 2.4 ml of SonoVue® (Bracco, Altana Pharma GmbH, Italy) were administered to each patient intravenously as a bolus injection. Results: Out of 30 patients, 21 endoleaks were identified in CTA (6 type I or III, 15 type II), 22 in CHI. Thus, sensitivity for CHI was therefore 99%, its specificity 85% (Spearman correlation coefficient (CC) 0.92). In follow-up the localizations of endoleak type I or III exclusively detected by CHI were confirmed as true positive by angiography. Due to its dynamic characteristic CHI seemed to be more helpful in characterization of endoleaks than CTA. In case of a rupture after reintervention a type III endoleak leads to prompt intervention before receiving the result of the CT scan. Altogether, CHI failed to identify 1 combined type I and II endoleak (sensitivity 0.99). Both, CCDS and PD were positive only in 6/30 patients (CC 0.33 and 0.39). Interestingly the application of contrast agent doubles the detection rate of endoleaks (12/30) in CCDS and PD (CC 0.39). Conclusion: Contrast harmonic imaging (CHI) compared to computed tomography angiography (CTA) accurately depicts endoleaks after endovascular abdominal aneurysm repair and stent-graft procedure in dissected and ulcerated aorta. It seems to be superior in characterization of the type of endoleaks and can be established in order to reduce iodized contrast agent and radiation exposure in follow-up. In contrast to CTA scan CHI can be offered to patients with chronic renal insufficiency and allows a dynamic examination and a perfusion analysis. Show more

Keywords: Contrast-enhanced ultrasound, endovascular abdominal aneurysm repair, endoleak, surveillance

DOI: 10.3233/CH-2009-1226

Citation: Clinical Hemorheology and Microcirculation, vol. 43, no. 1-2, pp. 119-128, 2009

Authors: Clevert, D.-A. | Horng, A. | Clevert, D.-A. | Jung, E.M. | Sommer, W.H. | Reiser, M.

Article Type: Research Article

Abstract: Purpose: To evaluate the diagnostic results of different ultrasound techniques: B-scan, color-coded Doppler sonography (CCDS) and contrast-enhanced ultrasound in the diagnosis of abdominal aortic dissection in comparison to multislice computed tomography (MS-CT). Materials and methods: Between March 2006 and December 2008, 35 patients (28 males, 7 females) with a mean age of 58 years (range 37–87 years) with abdominal aortic dissection and 15 patients (11 males, 4 females) with a mean age of 53 years (range 42–78 years) without abdominal aortic dissection as a control group were examined with B-scan, CCDS and contrast-enhanced ultrasound (CEUS) after injection of 1.0–1.2 …cc of SonoVue (Bracco, Italy). The examinations were performed using a Sequoia 512 (Siemens/Acuson, Mountain View) system with CPS software. Standardized MS-CTA using a 16 or 64 row scanner (Somatom Sensation 16 or 64, Siemens Medical Systems, Forchheim, Germany) served as the reference standard. Results: The sensitivity of B-scan and CCDS for detecting abdominal aortic dissections were both 23/35 (68%); for contrast-enhanced ultrasound it was 34/35 (97%). Dissection membrane, differentiation of true and false lumen and flow direction within the true and false lumen were better detected by CEUS than by CCDS. The lack of angle dependence of the US probe and lack of flow and pulsations artifacts in CEUS made the examination procedure easier. All findings were confirmed by MS-CT. Conclusion: With contrast-enhanced ultrasound, diagnostic accuracy sensitivity and specificity for the diagnosis of abdominal aortic dissections is improved as compared to B-scan and CCDS. Dissection membrane and flow within the true and false lumen are clearly differentiated by CEUS. Thus CEUS is a promising alternative for patients whose condition does not allow an examination by CTA. Show more

Keywords: Dissection, contrast-enhanced ultrasound, MS-CT

DOI: 10.3233/CH-2009-1227

Citation: Clinical Hemorheology and Microcirculation, vol. 43, no. 1-2, pp. 129-139, 2009

Authors: Girlich, C. | Jung, E.M. | Iesalnieks, I. | Schreyer, A.G. | Zorger, N. | Strauch, U. | Schacherer, D.

Article Type: Research Article

Abstract: Patients with inflammatory bowel disease (IBD) often undergo several radiologic imaging studies, which – with the exception of magnetic resonance imaging (MRI) and B-scan ultrasound (US) – subject patients to ionizing radiation. With contrast enhanced ultrasound microvascular imaging of the bowel is possible. Hence, the aim of our study was to assess the perfusion pattern of inflamed bowel walls in Crohn's disease compared with healthy volunteers quantitatively using a specific quantification software. We evaluated 4 volunteers and 20 patients with proven Crohn's disease, who went through an active episode based on clinical symptoms and complementary imaging by MRI (19 …patients) and computed tomography (1 patient), respectively, with dynamic contrast-enhanced ultrasound (CEUS) using a second generation contrast agent (SonoVue® , Bracco, Germany). Retrospectively, we applied the quantification software Qontrast® (Bracco, Italy) to obtain contrast-enhanced sonographic perfusion maps for each lesion. Patients had significant higher peak values (median 46.86, lower quartile 37.91, upper quartile 53.20) and significant higher regional blood volume (median 2133.65, lower quartile 1202.90, upper quartile 2820.44) than volunteers. Considering the very low peak value of the healthy, it is easy to understand that the time-to-peak was significantly shorter in the volunteers (median 4.45, lower quartile 1.82, upper quartile 6.88) than in the patients (median 12.15, lower quartile 9.18, upper quartile 15.74). Our study showed clear differences between inflamed and normal bowel wall vascularity regarding all perfusion parameters. These results show that a quantitative assessment of the bowel wall vascularisation and inflammation, respectively, is possible. The software used here enables us to collect data, not only in a semi-quantitative but also in a reproducible, quantitative manner which is comparable with the evaluation of CT or MRI generated data. Show more

Keywords: Contrast-enhanced ultrasound, Crohn's disease, quantitative perfusion analysis, inflammatory bowel disease

DOI: 10.3233/CH-2009-1228

Citation: Clinical Hemorheology and Microcirculation, vol. 43, no. 1-2, pp. 141-148, 2009

Authors: Franke, R.P. | Fuhrmann, R. | Hiebl, B. | Mrowietz, C. | Jung, F.

Article Type: Research Article

Abstract: The permeability of a material is described by the amount of substances (gases, liquids, particles) passing through pores and/or interstices of the material in a certain time. In medicine and biotechnology the permeability is given usually as the amount of water (ml × cm−2 × min−1 ) permeating per area and time unit through the material. Vascular prostheses are described e.g. as high porous prostheses (e.g. Dacron™: 1500–4000 (ml × cm−2 × min−1 )) or as low porous prostheses (e.g. ePTFE: 200–1000 (ml × cm−2 × min−1 )). The permeability of blood capillaries is characterized by …the exchange of nutrients, metabolites and breathing gases. Capillary permeability and the transport of the permeates through tissues are the key processes for the supply of organs and tissues where especially the protein transport through tissues is described by diffusive and/or convective terms. The vascular permeability is governed by the permeability of the intimal endothelial cells. The major influence is exerted by the interendothelial binding which can change drastically in a very short time. This is demonstrated by the fast development of interstitial lung oedema in case of septical shock. The permeability is an integral indicator of tissue and organ function. It is possible to assess the permeability of native and engineered tissues precisely with a recently developed system. First results will be shown. Show more

Keywords: Vascular permeability, water, culture medium, endothelial cells, nylon 6,6, PETP

DOI: 10.3233/CH-2009-1229

Citation: Clinical Hemorheology and Microcirculation, vol. 43, no. 1-2, pp. 149-155, 2009

Authors: Hoepken, S. | Fuhrmann, R. | Jung, F. | Franke, R.P.

Article Type: Research Article

Abstract: A variety of medical grade polymeric materials are used in tissue engineering and biomedical technology. Dense non-porous polymeric foils were used as substrates for endothelial cell layers. Half a the test samples (polymers and control materials) were seeded with bovine corneal endothelial cells (BCEC) which more or less covered the substrates with an extracellular matrix (ECM) in the consecutive culturing period. Afterwards the ECM covered as well as the uncovered materials were seeded with human umbilical venous endothelial cells (HUVEC). HUVEC seeded samples were cultured either under static or under dynamical conditions in a cone/plate rheometer with a mean low …arterial shear stress of 8.2 dyn/cm2 to simulate the flow conditions in a coronary vein graft. With the exemption of polyvinyl chloride all other materials could be coated with ECM at least partially. Under static conditions the best results with respect to complete coverage with ECM and HUVEC were seen on polyester and polyurethane. Under shear load, however, the complete HUVEC layer together with the ECM detached from the polymer surface within a short time. ECM and HUVEC remained no longer than 43 minutes on anyone of the materials tested. The materials as supplied and tested were clearly not appropriate as implants in contact to the flowing blood. Show more

Keywords: Endothelial cells, extracellular matrix, shear stress, vascular graft, polymers, biomedical materials

DOI: 10.3233/CH-2009-1230

Citation: Clinical Hemorheology and Microcirculation, vol. 43, no. 1-2, pp. 157-166, 2009

Authors: Leithäuser, B. | Mrowietz, C. | Hiebl, B. | Pindur, G. | Jung, F.

Article Type: Research Article

Abstract: Background: Oral anticoagulants are routinely used for prevention of thromboembolism in cardiac, arterial or venous diseases. Hemorrhages are serious treatment complications, frequently occurring under long-term and/or high-dose regiments. From animal experiments it is known that coumarin-type anticoagulants may cause capillary dilatation and increased permeability, red blood cell extravasation and punctate bleeding. Controlled human trials are lacking. Methods: 31 patients under oral anticoagulation were examined by video capillary microscopy. 52 patients with comparable diseases and treatment but without oral anticoagulation served as controls. Nailfold capillaries of four fingers of each hand were examined and analyzed off-line according to the following …criteria: (1) numbers of capillaries investigated, (2) numbers of capillary bleedings, and (3) bleeding incidence (bleedings per 100 capillaries). Results: In 23 out of 31 patients (74.2%) capillary bleedings were observed. The bleeding incidence ranged from 0.33 to 4.29 per 100 capillaries. In contrast, only 4 out of 52 controls were detected with capillary bleedings (2.1%, p<0.001). The bleeding incidence was 0.34–2.41. In patients on anticoagulation there was no correlation between the number of capillary bleedings and the INR or Quick values. During a two year follow-up of patients on oral anticoagulation no significant difference was found in terms of clinically obvious bleedings in patients with or without capillary bleedings. Conclusion: This study shows that capillary bleedings can be demonstrated in patients on oral anticoagulation. Bleedings occur independent of the INR-value. Thus, other factors than the vitamin-k-dependent coagulation effect seem to be causal for the damage of microvessels. Further, the evidence of capillary bleedings is not a prognostic indicator for future hemorrhage. Show more

Keywords: Microcirculation, capillary, bleeding, cumarin

DOI: 10.3233/CH-2009-1231

Citation: Clinical Hemorheology and Microcirculation, vol. 43, no. 1-2, pp. 167-171, 2009

Authors: Hiebl, B. | Mrowietz, C. | Braune, S. | Franke, R.P. | Plendl, J. | Jung, F.

Article Type: Research Article

Abstract: Several methods are available today for the investigation of microcirculation in animal models, but they can be invasive and time-consuming depending on the area investigated. In particular, non-invasive methods that can be conducted rapidly and without dye or tracer injections are in demand. The cutaneous microcirculation can be easily studied in the dorsal corium limbi of the third toe of the porcine forelimb using intravital microscopy – analogous to nail fold capillary microscopy in humans. The capillary microscopy system consists of a reflected-light microscope with a cold light source, green and infrared filters and a video camera. The video …sequences were recorded using the image capture system Framegrabber (Imagenation PXC-200) and a PC (with an Intel Core 2 Duo processor, 1024 MB RAM, 160 GB hard disk, Windows XP Pro), and stored via a DVD recorder (Panasonic LQ-MD800). Quantification of capillary erythrocyte flow velocities was performed using the computer-assisted image analysis system Cap Image Version 8.5 which includes a movie tool as a video sequence storage medium. The method allows estimation of capillary density and tortuosity as well as capillary circulation in the anesthetized pig within a few minutes. First measurements were made after anesthesia induction followed by further measurements during anesthesia maintenance (3 minutes each). No differences in capillary circulation were found. The present method is thus very well suited for long-term microcirculation measurements in pigs, e.g., to evaluate therapeutic interventions in the ischemic limb model. Show more

Keywords: Microcirculation, animal model, capillary microscopy

DOI: 10.3233/CH-2009-1232

Citation: Clinical Hemorheology and Microcirculation, vol. 43, no. 1-2, pp. 173-179, 2009

Authors: Franke, R.P. | Fuhrmann, R. | Hiebl, B. | Jung, F.

Article Type: Research Article

Abstract: Besides the desirable effect of roentgen ray absorption radiographic contrast media (RCM) can also have varying adverse effects. Under discussion, as a possible cause, are microcirculatory disorders resulting from morphological alterations in erythrocytes and endothelial cells. Therefore, the contrast media-induced release of vasoactive substances (prostacyclin, endothelin-1, and nitric oxide (NO)) from human endothelial cells (HUVEC) induced by two commercially available RCMs (Iodixanol 320, Iomeprol 350) was tested in a controlled in-vitro study. The results show that RCMs lead to endothelial cell trauma in vitro, which is apparent in the release of prostacyclin and endothelin-1, while NO release was …not affected. The endothelin-1 release after incubation with Iodixanol was similar to the release in the control cultures. In comparison, lower endothelin-1 levels were measured in the cultures incubated with Iomeprol at all 3 time points indicating a more significant cell trauma. Prostacyclin release – also an indicator of traumatization of endothelial cells – increased after addition of both contrast agents. The highest release was found after incubation with Iomeprol 350. Show more

Keywords: Endothelin, prostacyclin, NO, radiographic contrast media, primary human endothelial cells

DOI: 10.3233/CH-2009-1233

Citation: Clinical Hemorheology and Microcirculation, vol. 43, no. 1-2, pp. 181-187, 2009