Pre-therapeutic factors for predicting survival after radioembolization: a single-center experience in 389 patients.

PURPOSE: To determine pre-therapeutic predictive factors for overall survival (OS) after yttrium (Y)-90 radioembolization (RE). METHODS: We retrospectively analyzed the pre-therapeutic characteristics (sex, age, tumor entity, hepatic tumor burden, extrahepatic disease [EHD] and liver function [with focus on bilirubin and cholinesterase level]) of 389 consecutive patients with various refractory liver-dominant tumors (hepatocellular carcinoma [HCC], cholangiocarcinoma [CCC], neuroendocrine tumor [NET], colorectal cancer [CRC] and metastatic breast cancer [MBC]), who received Y-90 radioembolization for predicting survival. Predictive factors were selected by univariate Cox regression analysis and subsequently tested by multivariate analysis for predicting patient survival. RESULTS: The median OS was 356 days (95% CI 285-427 days). Stable disease was observed in 132 patients, an objective response in 71 (one of which was complete remission) and progressive disease in 122. The best survival rate was observed in patients with NET, and the worst in patients with MBC. In the univariate analyses, extrahepatic disease (P < 0.001), large tumor burden (P = 0.001), high bilirubin levels (>1.9 mg/dL, P < 0.001) and low cholinesterase levels (CHE <4.62 U/I, P < 0.001) at baseline were significantly associated with poor survival. Tumor entity, tumor burden, extrahepatic disease and CHE were confirmed in the multivariate analysis as independent predictors of survival. Sex, applied RE dose and age had no significant influence on OS. CONCLUSIONS: Pre-therapeutic baseline bilirubin and CHE levels, extrahepatic disease and hepatic tumor burden are associated with patient survival after RE. Such parameters may be used to improve patient selection for RE of primary or metastatic liver tumors.

Robust evidence for long-term survival with 90Y radioembolization in chemorefractory liver-predominant metastatic colorectal cancer.

OBJECTIVES: Our aim was to provide further evidence for the efficacy/safety of radioembolization using yttrium-90-resin microspheres for unresectable chemorefractory liver metastases from colorectal cancer (mCRC). METHODS: We followed 104 consecutively treated patients until death. Overall survival (OS) was calculated from the day of the first radioembolization procedure. Response was defined by changes in tumour volume as defined by Response Evaluation Criteria in Solid Tumours (RECIST) v1.0 and/or a ≥30 % reduction in serum carcinoembryonic antigen (CEA) at 3 months. RESULTS: Survival varied between 23 months in patients who had a complete response to prior chemotherapy and 13 months in patients with a partial response or stable disease. Median OS also significantly improved (from 5.8 months to 17.1 months) if response durability to radioembolization extended beyond 6 months. Patients with a positive trend in CEA serum levels (≥30 % reduction) at 3 months post-radioembolization also had a survival advantage compared with those who did not: 15.0 vs 6.7 months. Radioembolization was well tolerated. Grade 3 increases in bilirubin were reported in 5.0 % of patients at 3 months postprocedure. CONCLUSIONS: After multiple chemotherapies, many patients still have a good performance status and are eligible for radioembolization. This single procedure can achieve meaningful survivals and is generally well tolerated. KEY POINTS: • After multiple chemotherapies, many patients are still eligible for radioembolization (RE). • RE can achieve meaningful survival in patients with chemorefractory liver-predominant metastatic colorectal cancer (mCRC). • Tumour responsiveness to prior systemic treatments is a significant determinant of overall survival (OS) after RE. • Radioembolization in patients with a good performance status is generally well tolerated.

Renal Pseudoaneurysms and Arteriovenous Fistulas as a Complication of Nephron-Sparing Partial Nephrectomy: Technical and Functional Outcomes of Patients Treated With Selective Microcoil Embolization During a Ten-Year Period.

PURPOSE: The aim of this study was to evaluate the clinical and functional outcomes in patients who underwent selective interventional embolization of renal pseudoaneurysms or arteriovenous fistulas at our center. MATERIALS AND METHODS: Our retrospective analysis included all consecutive patients who received selective transcatheter embolization of renal pseudoaneurysms or arteriovenous fistulas after partial nephrectomy in our department from January, 2003 to September, 2013. The technical and clinical success rate and functional outcome of every procedure was collected and analyzed. Furthermore, the change in renal parenchymal volume before and after embolization was determined in a subgroup. RESULTS: A total of 1425 patients underwent partial nephrectomy at our hospital. Of these, 39 (2.7 %) were identified with a pseudoaneurysm or an arteriovenous fistula after partial nephrectomy. The diagnosis of the vascular lesions was made by means of biphasic CT or CEUS. Technical success by means of selective microcoil embolization was achieved in all 39 patients (100 %). Clinical success, defined as no need for further operation or nephrectomy during follow-up, was achieved in 35 of 39 patients (85.7 %). Renal function, as measured by eGFR before and after the intervention, did not change significantly. However, a mean loss of parenchymal volume of 25.2 % was observed in a subgroup. No major or minor complications were attributable to the embolization procedure. CONCLUSION: Transcatheter embolization is a promising method for treating vascular complications which may occur after partial nephrectomy. We confirm the high success rate of this technique while discussing renal functional outcomes and potential safety aspects. KEY POINTS: Arterial pseudoaneurysms and arteriovenous fistulas are rare but severe complications after partial nephrectomy. Selective microcoil embolization is a safe and effective kidney-preserving procedure for treating these complications. Embolization leads to a significant loss of renal parenchymal volume but not to a loss of renal function.

Evaluation of multimodality imaging using image fusion with MRI and CEUS in an experimental animal model.

PURPOSE: To evaluate the diagnostic benefits of multimodality imaging using image fusion with magnetic-resonance-imaging (MRI) and contrast-enhanced-ultrasound (CEUS) in an experimental small-animal-squamous-cell-carcinoma-model for the assessment of tissue hemodynamics and morphology. MATERIAL AND METHODS: Human hypopharynx-carcinoma-cells were injected subcutaneously into the left flank of 15 female athymic nude rats. After 10 daysof subcutaneous tumor growth, CEUS and MRI measurements were performed using a high-end-ultrasound-system and 3-T-MRI. After successful point-to-point or plan registration, the registered MR-images were simultaneously shown with the respective ultrasound sectional plane. Data evaluation was performed using the digitally stored video sequence data sets by two experienced radiologists using a subjective 5-point scale. RESULTS: CEUS and MRI are well-known techniques for the assessment of tissue hemodynamics (score: mean 3.8 ± 0.4 SD and score 3.8 ± 0.4 SD). Real-time image fusion of MRI and CEUS yielded a significant (p <  0.001) improvement in score (score 4.8 ± 0.4 SD). Reliable detection of small necrotic areas was possible in all animals with necrotic tumors. No significant intraobserver and interobserver variability was detected (kappa coefficient = +1). CONCLUSION: Image fusion of MRI and CEUS gives a significant improvement for reliable differentiation between different tumor tissue areas and simplifies investigations by showing the morphology as well as surrounding macro-/microvascularization.

Safety of Radioembolization with (90)Yttrium Resin Microspheres Depending on Coiling or No-Coiling of Aberrant/High-Risk Vessels.

PURPOSE: To evaluate the safety of radioembolization (RE) with (90)Yttrium ((90)Y) resin microspheres depending on coiling or no-coiling of aberrant/high-risk vessels. MATERIALS AND METHODS: Early and late toxicity after 566 RE procedures were analyzed retrospectively in accordance with the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE v3.0). For optimal safety, aberrant vessels were either coil embolized (n = 240/566, coiling group) or a more peripheral position of the catheter tip was chosen to treat right or left liver lobes (n = 326/566, no-coiling group). RESULTS: Clinically relevant late toxicities (≥ Grade 3) were observed in 1% of our overall cohort. The no-coiling group had significantly less "any" (P = 0.0001) or "clinically relevant" (P = 0.0003) early toxicity. There was no significant difference (P > 0.05) in delayed toxicity in the coiling versus the no-coiling group. No RE-induced liver disease was noted after all 566 procedures. CONCLUSION: RE with (90)Y resin microspheres is a safe and effective treatment option. Performing RE without coil embolization of aberrant vessels prior to treatment could be an alternative for experienced centers.

Evaluation of multimodality imaging using image fusion with ultrasound tissue elasticity imaging in an experimental animal model.

PURPOSE: To evaluate the ultrasound tissue elasticity imaging by comparison to multimodality imaging using image fusion with Magnetic Resonance Imaging (MRI) and conventional grey scale imaging with additional elasticity-ultrasound in an experimental small-animal-squamous-cell carcinoma-model for the assessment of tissue morphology. METHOD AND MATERIALS: Human hypopharynx carcinoma cells were subcutaneously injected into the left flank of 12 female athymic nude rats. After 10 days (SD ± 2) of subcutaneous tumor growth, sonographic grey scale including elasticity imaging and MRI measurements were performed using a high-end ultrasound system and a 3T MR. For image fusion the contrast-enhanced MRI DICOM data set was uploaded in the ultrasonic device which has a magnetic field generator, a linear array transducer (6-15 MHz) and a dedicated software package (GE Logic E9), that can detect transducers by means of a positioning system. Conventional grey scale and elasticity imaging were integrated in the image fusion examination. After successful registration and image fusion the registered MR-images were simultaneously shown with the respective ultrasound sectional plane. Data evaluation was performed using the digitally stored video sequence data sets by two experienced radiologist using a modified Tsukuba Elasticity score. The colors "red and green" are assigned for an area of soft tissue, "blue" indicates hard tissue. RESULTS: In all cases a successful image fusion and plan registration with MRI and ultrasound imaging including grey scale and elasticity imaging was possible. The mean tumor volume based on caliper measurements in 3 dimensions was ~323 mm3. 4/12 rats were evaluated with Score I, 5/12 rates were evaluated with Score II, 3/12 rates were evaluated with Score III. There was a close correlation in the fused MRI with existing small necrosis in the tumor. None of the scored II or III lesions was visible by conventional grey scale. CONCLUSION: The comparison of ultrasound tissue elasticity imaging enables a secure differentiation between different tumor tissue areas in comparison to image fusion with MRI in our small study group. Therefore ultrasound tissue elasticity imaging might be used for fast detection of tumor response in the future whereas conventional grey scale imaging alone could not provide the additional information. By using standard, contrast-enhanced MRI images for reliable and reproducible slice positioning, the strongly user-dependent limitation of ultrasound tissue elasticity imaging may be overcome, especially for a comparison between baseline and follow-up measurements.

[Computed tomography guidance: fluoroscopy and more]. / CT-Steuerung: Fluoroskopie und mehr.

Although ultrasound and magnetic resonance imaging are competitive imaging modalities for the guidance of needle-based interventions, computed tomography (CT) is the only modality suitable for image-guided interventions in all regions of the body, including the lungs and bone. The ongoing technical development of CT involves accelerated image acquisition, significantly improved spatial resolution, CT scanners with an extended gantry diameter, acceleration of the procedure through joystick control of relevant functions of interventional CT by the interventional radiologist and tube current modulation to protect the hands of the examiner and radiosensitive organs of the patient. CT fluoroscopy can be used as a real-time method (the intervention is monitored under continuous CT fluoroscopy) or as a quick check method (repeated acquisitions of individual CT fluoroscopic images after each change of needle or table position). For the two approaches, multislice CT fluoroscopy (MSCTF) technique with wide detectors is particularly useful because even in the case of needle deviation from the center slice the needle tip is simultaneously visualised in the neighboring slices. With the aid of this technique a precise placement of interventional devices is possible even in angled access routes and in the presence of pronounced respiratory organ movements. As the reduction of CT fluoroscopy time significantly reduces radiation exposure for the patient and staff, the combination of a quick check technique and a low milliampere technique with multislice CT fluoroscopy devices is advantageous.

Comparison of consecutive bolus tracking and flash replenishment measurements for the assessment of tissue hemodynamics using contrast-enhanced ultrasound (CEUS) in an experimental human squamous cell carcinoma model.

PURPOSE: To evaluate "bolus-tracking" (BT) and "flash-replenishment" (FR) for the assessment of tissue hemodynamics by contrast-enhanced ultrasound (CEUS) in an experimental small-animal-squamous-cell-carcinoma-model. Since the underlying tissue is the same, strong correlations between parameter outcomes of both techniques are expected. METHODS AND MATERIALS: Human hypopharynx-carcinoma-cells were subcutaneously injected into the left flank of 18 female athymic-nude-rats. After 10 days of subcutaneous tumour growth, bolus tracking and flash-replenishment measurements were performed consecutively in the same imaging plane in each rat after bolus-injection of SonoVue via the lateral tail vein using a high-end ultrasound system with a 15 MHz probe. Video-sequences were analysed with dedicated software (VueBox®, Bracco-Suisse®). From BT measurements, the parameters peak enhancement (PEBT), wash-in area-under-the-curve (Wi-AUCBT), mean transit time (MTTBT), wash-in-rate (WiRBT) and perfusion-index (Wi-PIBT) were derived; FR yielded estimates of relative-blood-volume (rBVFR), mean transit time MTTFR, relative blood flow rBFFR and wash-in rate Wi-RFR. RESULTS: In all rats, BT and FR measurements could be completed successfully. Highly significant correlations were observed between rBVFR and PEBT, rBVFR and Wi-AUCBT, rBVFR and MTTBT, rBVFR and WiPIBT, MTTFR and MTTBT, rBFFR and PEBT, rBFFR and Wi-AUCBT, rBFFR and WiRBT, rBFFR and WiPIBT, WiRFR and PEBT, WiRFR and Wi-AUCBT, WiRFR and WiRBT and WiRFR and WiPIBT. CONCLUSION: Whereas bolus tracking can be used in a wide range of modalities including CEUS, CT and MR, FR as a technique for the assessment of tissue hemodynamics is unique to CEUS. Although BT and FR yield different parameters, the underlying tissue hemodynamics are equal. In this work, we were able to demonstrate strong correlations between different parameters of both modalities in a small-animal-tumor-model, indicating that flash-replenishment is a valid alternative to the more established bolus-tracking technique. Although the lack of absolute, quantitative parameters hinders a direct comparison of both modalities, FR and BT should both be suitable for a relative comparison, e.g. between baseline and follow-up examinations.

Image fusion in the management of thermal tumor ablation of the liver.

PURPOSE: The purpose of this study was to evaluate whether image fusion with contrast enhanced ultrasound (CEUS) and CT is effective in the pre-, intra- and post-interventional management of liver lesions during microwave or radiofrequency ablation. METHODS AND MATERIALS: Fifteen patients with a single hepatocellular carcinoma (HCC) up to 3 cm diameter, identified on both contrast-enhanced CT (Siemens Somatom Definition AS and Definition Edge, Siemens Healthcare, Erlangen, Germany) and ultrasound (Siemens ACUSON S2000™ or S3000™, Siemens Healthcare, Erlangen, Germany) were retrospectively enrolled between July 2011 and May 2012. Either automatic registration or plane match registration was chosen on CT and ultrasound for the pre-, intra- and postinterventional management of all treated liver lesions during microwave or radiofrequency ablation. Using conventional ultrasound B-mode, CEUS and image fusion including B-mode and CEUS the detectability of the liver lesions was evaluated semi-quantitatively by comparing the image sequences in a consensus reading. Eight patients underwent radiofrequency ablation and seven patients underwent microwave ablation. RESULTS: All patients were examined using all diagnostic ultrasound tools of the study. The results show that the procedure is easy and convenient to perform, as well as efficient. The co-registration procedure took approximately 5 to 10 minutes depending on the amount of DICOM volume-data and the habitus of the patient. The results show that the use of image fusion with CT and contrast-enhanced ultrasound could improve the diagnostic assessment capabilities in comparison to the examination without image fusion in the pre-, intra- and postinterventional management of malignant liver lesions during thermal ablation. CONCLUSION: Percutaneous thermal ablation guided by contrast-enhanced ultrasound and image fusion seems to be an efficient approach for malignant liver lesions especially if these are not clearly demarcated by B-mode. The use of the image fusion technique in the pre-, intra- and postinterventional management can increase operator confidence, the accuracy of the procedure, and technical success in real time.

[Ultrasound-guided image fusion with computed tomography and magnetic resonance imaging. Clinical utility for imaging and interventional diagnostics of hepatic lesions]. / Ultraschallgestützte Bildfusion mittels CT und MRT. Klinische Bedeutung für die bildgebende und interventionelle Diagnostik von Leberläsionen.

Abdominal ultrasound is often the first-line imaging modality for assessing focal liver lesions. Due to various new ultrasound techniques, such as image fusion, global positioning system (GPS) tracking and needle tracking guided biopsy, abdominal ultrasound now has great potential regarding detection, characterization and treatment of focal liver lesions. Furthermore, these new techniques will help to improve the clinical management of patients before and during interventional procedures. This article presents the principle and clinical impact of recently developed techniques in the field of ultrasound, e.g. image fusion, GPS tracking and needle tracking guided biopsy and discusses the results based on a feasibility study on 20 patients with focal hepatic lesions.

Practical vascular anatomy in the preparation of radioembolization.

As the incidence of primary and metastatic liver cancer continues to increase, the use of minimally invasive techniques as a treatment option is becoming more common. Radioembolization, a form of intra-arterial brachytherapy, is a technique where particles of glass or resin, impregnated with the isotope 90yttrium (90Y), are infused through a catheter directly into the hepatic arteries. This modality is based on the fact that hepatic malignancies receive their blood supply from the hepatic artery, whereas normal hepatocytes are perfused mostly from the portal circulation, which allows delivery of high doses to the tumor vasculature with relative sparing of normal liver tissue. This has been shown to be effective for both primary and metastatic tumors. A variety of complications may be related to hepatic intra-arterial treatments, especially to the gastroduodenal region. These complications are known to come from inadvertent extrahepatic infusion of 90Y particles, through arteries originating from the hepatic arterial branches such as the falciform artery, cystic artery, arteries from the pancreaticoduodenal arcade, gastroduodenal artery, or right gastric artery. Surgeons and interventional radiologists rely on accurate imaging and assessment of the hepatic arterial supply. It is important to know the common anatomic variations and technical considerations before radioembolization. We recommend an aggressive occlusion of all the above-mentioned arteries; further, clinicians should watch out for any other aberrant branches, and if in doubt, they ought to be coiled.

[Latest developments in ultrasound of the liver]. / Die letzten Entwicklungen beim Ultraschall der Leber.

Abdominal ultrasound (US) is often the first-line imaging modality used to assess focal liver lesions. Due to various new gray-scaled US techniques, such as tissue harmonic imaging (THI), spatial compounding technique and speckle reduction technique, as well as contrast-enhanced techniques, abdominal ultrasound nowadays has great potential regarding detection and characterization of focal liver lesions. Furthermore, image fusion with computed tomography (CT), magnetic resonance imaging (MRI) and 3D ultrasound will most likely help to improve clinical management before and after interventional procedures. This article illustrates the principles and clinical impact of recently developed techniques in the field of ultrasound.

[Contrast-enhanced ultrasound in animal models]. / Kontrastverstärkter Ultraschall der Skelettmuskulatur.

In the past the detection of tumor perfusion was achieved solely via invasive procedures, such as intravital microscopy or with the help of costly modalities, such as multidetector computed tomography (MDCT), magnetic resonance tomography (MRT) or the combined use of positron emission tomography and computed tomography (PET/CT). Ultrasound offers the non-invasive display of organs without usage of ionizing radiation and it is widely available. However, colour-coded ultrasound and power Doppler do not allow the detection of tumor microcirculation. The introduction of contrast-enhanced ultrasound (CEUS) as well as new high-frequency ultrasound probes made it possible to detect and quantify tumor microcirculation with high resolution. CEUS has been used clinically on human beings for more than 10 years. During the last years different tumor models in experimental animals were used for the establishment of this new technique, e.g. in rats, hamsters and mice. CEUS allows the detection of functional parameters, such as the angiogenetic metabolic status of tissue pretreatment and posttreatment. Further research is required to solve the problems of absolute quantification of these perfusion parameters to allow the comparison of CEUS with other modalities (e.g. MRT and CT).

[Contrast-enhanced ultrasound imaging of the carotid artery]. / Kontrastverstärkte Ultraschallbildgebung der A. carotis.

A conventional grey scale, Doppler sonography and color-coded Doppler ultrasound examination should be the first step in the diagnosis of the vessels supplying the brain and have a major impact in diagnostic imaging. This ultrasound examination allows the simultaneous acquisition of morphologic and hemodynamic information with high spatial and temporal resolution. Most of the pathological changes of the extracranial arteries can thus be reliably detected. Contrast-enhanced ultrasound (CEUS) is a promising new non-invasive method for the diagnosis and follow-up of complex carotid abnormalities. In addition to improving current carotid structural scans, CEUS has the potential to improve or provide additional information on carotid arterial diseases, such as the reliable differentiation between internal carotid artery (ICA) occlusion and pseudo-occlusion, improved visualization of in-stent stenosis, extracranial ICA aneurysms and carotid dissection.In this article the contribution of color-coded duplex ultrasound and CEUS in assessing various pathologies of the carotid artery will be addressed.

Non-invasive contrast enhanced ultrasound for quantitative assessment of tumor microcirculation. Contrast mixed mode examination vs. only contrast enhanced ultrasound examination.

PURPOSE: To evaluate the different ultrasound techniques for quantification of contrast enhanced ultrasound (CEUS) in an experimental rat prostate carcinoma model. METHOD AND MATERIALS: Prostate carcinoma (MLLB-2) cells were subcutaneously injected into the right flank of male rat (Charles River, Sulzfeld, Germany, 180 to 220 g body weight). Following 18 days of subcutaneous tumor growth 9 rats underwent CEUS examination. Real time CEUS was performed after a bolus injection of SonoVue (0.2 ml, Bracco, Italy) via the lateral tail vein using a high end ultrasound system (Siemens Sequoia 512®/Acuson, Mountain View) with an 15 Mhz probe. Two different CEUS techniques, pure contrast (pc) and contrast with background (cbg) examination, were analyzed (CPS-software). Exported signal intensity (SI)-time curves and the normalized area under the curve (AUC) for the active tumor tissue, whole tumor and necrosis were compared. RESULTS: The mean normalized AUC for the active tumor tissue and the whole tumor was 0.84 and 0.5 in the pure contrast examination group and 0.49 and 0.3 for the contrast examination with background signal. Therefore the signal intensity of the pc group was in every examination significant higher than of the cbg group (p < 0.02). The advantage of using the additional background information is to detect the anatomic landmarks in the solid tumor model in comparison to the pure contrast enhanced ultrasound examination. CONCLUSION: The complete extension of the tumor is much easier to detect with the cbg technique due to orientation of the anatomic landmarks. As the signal intensity of the pc group is always significant higher we recommend this technique for quantification of contrast enhanced ultrasound, especially for the follow up of tumor microcirculation.