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.

Dual energy CT allows for improved characterization of response to antiangiogenic treatment in patients with metastatic renal cell cancer.

OBJECTIVES: To evaluate the potential role of dual energy CT (DECT) to visualize antiangiogenic treatment effects in patients with metastatic renal cell cancer (mRCC) while treated with tyrosine-kinase inhibitors (TKI). METHODS: 26 patients with mRCC underwent baseline and follow-up single-phase abdominal contrast enhanced DECT scans. Scans were performed immediately before and 10 weeks after start of treatment with TKI. Virtual non-enhanced (VNE) and colour coded iodine images were generated. 44 metastases were measured at the two time points. Hounsfield unit (HU) values for VNE and iodine density (ID) as well as iodine content (IC) in mg/ml of tissue were derived. These values were compared to the venous phase DECT density (CTD) of the lesions. Values before and after treatment were compared using a paired Student's t test. RESULTS: Between baseline and follow up, mean CTD and DECT-derived ID both showed a significant reduction (p < 0.005). The relative reduction measured in percent was significantly greater for ID than for CTD (49.8 ± 36,3 % vs. 29.5 ± 20.8 %, p < 0.005). IC was also significantly reduced under antiangiogenic treatment (p < 0.0001). CONCLUSIONS: Dual energy CT-based quantification of iodine content of mRCC metastases allows for significantly more sensitive and reproducible detection of antiangiogenic treatment effects. KEY POINTS: • A sign of tumour response to antiangiogenic treatment is reduced tumour perfusion. • DECT allows visualizing iodine uptake, which serves as a marker for vascularization. • More sensitive detection of antiangiogenic treatment effects in mRCC is possible.

[Therapy monitoring of neoadjuvant therapy with MRI. RECIST and functional imaging]. / Therapiemonitoring im MRT unter neoadjuvanter Therapie. RECIST und funktionelle Bildgebung.

CLINICAL/METHODICAL ISSUE: Neoadjuvant chemotherapy is increasingly being applied in patients with operable breast cancer. Thus, an early prediction of response to neoadjuvant chemotherapy is of high relevance. STANDARD RADIOLOGICAL METHODS: The interobserver variability of clinical examination, mammography and ultrasonography in the assessment of response to neoadjuvant chemotherapy is high. METHODICAL INNOVATIONS: Magnetic resonance imaging (MRI) allows the assessment of functional parameters in addition to changes in tumor size and morphology. PERFORMANCE: A reliable therapy response monitoring aims at optimizing individualized patient care. ACHIEVEMENTS: This paper summarizes current guidelines for the assessment of response to neoadjuvant chemotherapy in breast cancer according to the response evaluation criteria in solid tumors (RECIST). Furthermore, the technical principles of MRI-based therapy monitoring are described and an overview of the clinical studies that have assessed the feasibility of functional MRI in response to treatment evaluation is given. PRACTICAL RECOMMENDATIONS: The technology of functional MRI offers promising results concerning therapy response monitoring. However, the level of evidence is not sufficiently evaluated for the technologies of functional MRI presented here.

[PET-MR in patients with glioblastoma multiforme]. / PET-MR bei Patienten mit Glioblastoma multiforme.

Glioblastoma multiforme (GBM) is the most common and most aggressive primary tumor of the brain. In recent years newer therapeutic approaches have been developed. To allow for an optimized treatment planning it is important to precisely delineate necrotic tissue, edema and vital tumor tissue and to identify the most aggressive parts of the GBM. The magnetic resonance (MR) portion of an MR-positron emission tomography (PET) examination in patients with GBM should consist of both structural and functional sequences including diffusion-weighted and perfusion sequences. The use of (18)F-fluorodeoxyglucose ((18)F-FDG) is limited in patients with gliomas as glucose metabolism is already physiologically high in parts of the brain but (18)F-FDG is nevertheless a commonly used radiopharmaceutical for neuro-oncological questions. (18)F-fluorothymidine reflects the cellular activity of thymidine kinase 1 and correlates with the expression of KI-67 as an index of mitotic activity. The nitroimidazole derivatives (18)F-fluoromisonidazole and (18)F-fluoroazomycin arabinoside ((18)F-FAZA) allow the detection of hypoxic areas within the tumor. In recent years amino acid tracers, such as (18)F-fluoroethyltyrosine are increasingly being used in the diagnosis of gliomas. The simultaneous PET-MR image acquisition allows new approaches, e.g. motion correction by the simultaneous acquisition of MR data with a high temporal resolution and an improved quantification of the PET signal by integrating the results of functional MR sequences. Moreover, the simultaneous acquisition of these two time-consuming methods leads to reduced imaging times for this, often severely ill patient group.

[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).

Artificial intelligence assistance improves reporting efficiency of thoracic aortic aneurysm CT follow-up.

OBJECTIVE: Follow-up of aortic aneurysms by computed tomography (CT) is crucial to balance the risks of treatment and rupture. Artificial intelligence (AI)-assisted radiology reporting promises time savings and reduced inter-reader variabilities. METHODS: The influence of AI assistance on the efficiency and accuracy of aortic aneurysm reporting according to the AHA / ESC guidelines was quantified based on 324 AI measurements and 1944 radiological measurements: 18 aortic aneurysm patients, each with two CT scans (arterial contrast phase, electrocardiogram-gated) with an interval of at least six months have been included. One board-certified radiologist and two residents (8/4/2 years of experience in vascular imaging) independently assessed aortic diameters at nine landmark positions. Aneurysm extensions were compared with original CT reports. After three weeks washout period, CTs were re-assessed, based on graphically illustrated AI measurements. RESULTS: Time-consuming guideline-compliant aortic measurements revealed additional affections of the root / arch for 80 % of aneurysms that had initially been reported to be limited to the ascending aorta. AI assistance reduced mean reporting time by 63 % from 13:01 to 04:46 min including manual corrections of AI measurements (performed for 33.6 % of all measurements with predominance at the sinuses of Vasalva). AI assistance reduced total diameter inter-reader variability by 42.5 % (0.42 / 1.16 mm with / without AI assistance, mean of all patients and landmark positions, significant reduction for 6 out of 9 measuring positions). Conventional and AI-assisted quantification aneurysm progress varied to small extent (mean of 0.75 mm over all patients / landmark positions) not significantly exceeding radiologist's inter-reader variabilities. CONCLUSIONS: Guideline-compliant aorta measurement is crucial to report detailed aneurysm extension which might affect the strategy of interventional repair. AI assistance promises improved reporting efficiency and has high potential to reduce radiologist's inter-reader variabilities that can hamper diagnostic follow-up accuracy. KEY POINT: The time-consuming guideline-compliant aorta aneurysm assessment is crucial to report aneurysm extension in detail; AI-assisted measurement reduces reporting time, improves extension evaluation and reduces inter-reader variability.

[Magnetic resonance imaging of pulmonary perfusion. Technical requirements and diagnostic impact]. / MRT der Lungenperfusion. Technische Voraussetzungen und diagnostischer Stellenwert.

With technical improvements in gradient hardware and the implementation of innovative k-space sampling techniques, such as parallel imaging, the feasibility of pulmonary perfusion MRI could be demonstrated in several studies. Dynamic contrast-enhanced 3D gradient echo sequences as used for time-resolved MR angiography have been established as the preferred pulse sequences for lung perfusion MRI. With these techniques perfusion of the entire lung can be visualized with a sufficiently high temporal and spatial resolution. In several trials in patients with acute pulmonary embolism, pulmonary hypertension and airway diseases, the clinical benefit and good correlation with perfusion scintigraphy have been demonstrated. The following review article describes the technical prerequisites, current post-processing techniques and the clinical indications for MR pulmonary perfusion imaging using MRI.

Impact of fitting algorithms on errors of parameter estimates in dynamic contrast-enhanced MRI.

Parameter estimation in dynamic contrast-enhanced MRI (DCE MRI) is usually performed by non-linear least square (NLLS) fitting of a pharmacokinetic model to a measured concentration-time curve. The two-compartment exchange model (2CXM) describes the compartments 'plasma' and 'interstitial volume' and their exchange in terms of plasma flow and capillary permeability. The model function can be defined by either a system of two coupled differential equations or a closed-form analytical solution. The aim of this study was to compare these two representations in terms of accuracy, robustness and computation speed, depending on parameter combination and temporal sampling. The impact on parameter estimation errors was investigated by fitting the 2CXM to simulated concentration-time curves. Parameter combinations representing five tissue types were used, together with two arterial input functions, a measured and a theoretical population based one, to generate 4D concentration images at three different temporal resolutions. Images were fitted by NLLS techniques, where the sum of squared residuals was calculated by either numeric integration with the Runge-Kutta method or convolution. Furthermore two example cases, a prostate carcinoma and a glioblastoma multiforme patient, were analyzed in order to investigate the validity of our findings in real patient data. The convolution approach yields improved results in precision and robustness of determined parameters. Precision and stability are limited in curves with low blood flow. The model parameter v e shows great instability and little reliability in all cases. Decreased temporal resolution results in significant errors for the differential equation approach in several curve types. The convolution excelled in computational speed by three orders of magnitude. Uncertainties in parameter estimation at low temporal resolution cannot be compensated by usage of the differential equations. Fitting with the convolution approach is superior in computational time, with better stability and accuracy at the same time.

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.

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.

Quantification of pulmonary perfusion with free-breathing dynamic contrast-enhanced MRI--a pilot study in healthy volunteers.

PURPOSE: The assessment of pulmonary perfusion using dynamic contrast-enhanced (DCE) MRI is still limited in the clinical routine due to the necessity of breath holding. An acquisition technique for the quantitative assessment of pulmonary perfusion in free breathing was investigated in our study. MATERIALS AND METHODS: 10 healthy male volunteers underwent pulmonary DCE-MRI on a 1.5 T scanner. Each volunteer was examined twice: (a) in breath-hold half expiration and (b) during shallow free breathing. The pulmonary parenchyma was segmented automatically. The pulmonary plasma flow (PPF) and pulmonary plasma volume (PPV) were determined pixel-wise using a one-compartment model. RESULTS: All examinations were of diagnostic image quality. The measured mean values of the PPV were significantly lower in the breath-hold technique than during free breathing ((10.2 ±â€Š2.8) ml/100 ml vs. (12.7 ±â€Š3.9) ml/100 ml); p < 0.05). A significant difference was also observed between both PPF measurements (mean PPF (206.2 ±â€Š104.0) ml/100 ml/min in breath-hold technique vs. (240.6 ±â€Š114.0) ml/100 ml/min during free breathing; p < 0.05). CONCLUSION: Free-breathing DCE-MRI appears to be suitable for the quantitative assessment of the pulmonary perfusion in healthy volunteers. The proposed segmentation and quantification approach does not suffer from the increased motion, as compared to the breath-holding measurement. The increased PPV and PPF during free breathing are in accordance with the results of previous studies concerning breathing influence on perfusion parameters. Overall, free-breathing DCE-MRI may be a promising technique for the assessment of pulmonary perfusion in various pathologies.

Microbubbles as a scattering contrast agent for grating-based x-ray dark-field imaging.

In clinically established-absorption-based-biomedical x-ray imaging, contrast agents with high atomic numbers (e.g. iodine) are commonly used for contrast enhancement. The development of novel x-ray contrast modalities such as phase contrast and dark-field contrast opens up the possible use of alternative contrast media in x-ray imaging. We investigate using ultrasound contrast agents, which unlike iodine-based contrast agents can also be administered to patients with renal impairment and thyroid dysfunction, for application with a recently developed novel x-ray dark-field imaging modality. To produce contrast from these microbubble-based contrast agents, our method exploits ultra-small-angle coherent x-ray scattering. Such scattering dark-field x-ray images can be obtained with a grating-based x-ray imaging setup, together with refraction-based differential phase-contrast and the conventional attenuation contrast images. In this work we specifically show that ultrasound contrast agents based on microbubbles can be used to produce strongly enhanced dark-field contrast, with superior contrast-to-noise ratio compared to the attenuation signal. We also demonstrate that this method works well with an x-ray tube-based setup and that the relative contrast gain even increases when the pixel size is increased from tenths of microns to clinically compatible detector resolutions about up to a millimetre.

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.

MR-perfusion (MRP) and diffusion-weighted imaging (DWI) in prostate cancer: quantitative and model-based gadobenate dimeglumine MRP parameters in detection of prostate cancer.

BACKGROUND: Various MR methods, including MR-spectroscopy (MRS), dynamic, contrast-enhanced MRI (DCE-MRI), and diffusion-weighted imaging (DWI) have been applied to improve test quality of standard MRI of the prostate. PURPOSE: To determine if quantitative, model-based MR-perfusion (MRP) with gadobenate dimeglumine (Gd-BOPTA) discriminates between prostate cancer, benign tissue, and transitional zone (TZ) tissue. MATERIAL AND METHODS: 27 patients (age, 65±4 years; PSA 11.0±6.1 ng/ml) with clinical suspicion of prostate cancer underwent standard MRI, 3D MR-spectroscopy (MRS), and MRP with Gd-BOPTA. Based on results of combined MRI/MRS and subsequent guided prostate biopsy alone (17/27), biopsy and radical prostatectomy (9/27), or sufficient negative follow-up (7/27), maps of model-free, deconvolution-based mean transit time (dMTT) were generated for 29 benign regions (bROIs), 14 cancer regions (cROIs), and 18 regions of transitional zone (tzROIs). Applying a 2-compartment exchange model, quantitative perfusion analysis was performed including as parameters: plasma flow (PF), plasma volume (PV), plasma mean transit time (PMTT), extraction flow (EFL), extraction fraction (EFR), interstitial volume (IV) and interstitial mean transit time (IMTT). Two-sided T-tests (significance level p<0.05) discriminated bROIs vs. cROIs and cROIs vs. tzROIs, respectively. RESULTS: PMTT discriminated best between bROIs (11.8±3.0 s) and cROIs (24.3±9.6 s) (p<0.0001), while PF, PV, PS, EFR, IV, IMTT also differed significantly (p 0.00002-0.0136). Discrimination between cROIs and tzROIs was insignificant for all parameters except PV (14.3±2.5 ml vs. 17.6±2.6 ml, p<0.05). CONCLUSIONS: Besides MRI, MRS and DWI quantitative, 2-compartment MRP with Gd-BOPTA discriminates between prostate cancer and benign tissue with several parameters. However, distinction of prostate cancer and TZ does not appear to be reliable.