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