Albumin-based nanoparticles as contrast medium for MRI: vascular imaging, tissue and cell interactions, and pharmacokinetics of second-generation nanoparticles.

This multidisciplinary study examined the pharmacokinetics of nanoparticles based on albumin-DTPA-gadolinium chelates, testing the hypothesis that these nanoparticles create a stronger vessel signal than conventional gadolinium-based contrast agents and exploring if they are safe for clinical use. Nanoparticles based on human serum albumin, bearing gadolinium and designed for use in magnetic resonance imaging, were used to generate magnet resonance images (MRI) of the vascular system in rats ("blood pool imaging"). At the low nanoparticle doses used for radionuclide imaging, nanoparticle-associated metals were cleared from the blood into the liver during the first 4 h after nanoparticle application. At the higher doses required for MRI, the liver became saturated and kidney and spleen acted as additional sinks for the metals, and accounted for most processing of the nanoparticles. The multiple components of the nanoparticles were cleared independently of one another. Albumin was detected in liver, spleen, and kidneys for up to 2 days after intravenous injection. Gadolinium was retained in the liver, kidneys, and spleen in significant concentrations for much longer. Gadolinium was present as significant fractions of initial dose for longer than 2 weeks after application, and gadolinium clearance was only complete after 6 weeks. Our analysis could not account quantitatively for the full dose of gadolinium that was applied, but numerous organs were found to contain gadolinium in the collagen of their connective tissues. Multiple lines of evidence indicated intracellular processing opening the DTPA chelates and leading to gadolinium long-term storage, in particular inside lysosomes. Turnover of the stored gadolinium was found to occur in soluble form in the kidneys, the liver, and the colon for up to 3 weeks after application. Gadolinium overload poses a significant hazard due to the high toxicity of free gadolinium ions. We discuss the relevance of our findings to gadolinium-deposition diseases.

Evaluation of liver iron overload with R2* relaxometry with versus without fat suppression: both are clinically accurate but there are differences.

OBJECTIVES: To assess clinically relevant difference in hepatic iron quantification using R2* relaxometry with (FS) and without (non-FS) fat saturation for the evaluation of patients with suspected hepatic iron overload. METHODS: We prospectively enrolled 134 patients who underwent 1.5-T MRI R2* relaxometry with FS and non-FS gradient echo sequences (12 echoes, initial TE = 0.99 ms). Proton density fat fraction for the quantification of steatosis was assessed. Linear regression analyses and Bland-Altman plots including Lin's concordance correlation coefficient were performed for correlation of FS R2* with non-FS R2*. Patients were grouped into 4 severity classes of iron overload (EASL based), and agreement was evaluated by contingency tables and the proportion of overall agreement. RESULTS: A total of 41.8% of patients showed hepatic iron overload; 67.9% had concomitant steatosis; and 58.2% revealed no iron overload of whom 60.3% had steatosis. The mean R2* value for all FS data was 102.86 1/s, for non-FS 108.16 1/s. Linear regression resulted in an R-squared value of 0.99 (p < 0.001); Bland-Altman plot showed a mean R2* difference of 5.26 1/s (SD 17.82). The concordance correlation coefficient was only slightly lower for patients with steatosis compared with non-steatosis (0.988 vs. 0.993). The overall agreement between FS and non-FS R2* measurements was 94.8% using either method to classify patients according to severity of iron storage. No correlation between R2* and proton density fat fraction was found for both methods. CONCLUSION: R2* relaxometry showed an excellent overall agreement between FS and non-FS acquisition. Both variants can therefore be used in daily routine. However, clinically relevant differences might result when switching between the two methods or during patient follow-up, when fat content changes over time. We therefore recommend choosing a method and keeping it straight in the context of follow-up examinations. KEY POINTS: • Both variants of R2* relaxometry (FS and non-FS) may be used in daily routine. • Clinically relevant differences might result when switching between the two methods or during patient follow-up, when fat content changes over time. • It seems advisable choosing one method and keeping it straight in the context of follow-up examinations.

Does gadoxetate disodium affect MRE measurements in the delayed hepatobiliary phase?

OBJECTIVES: To assess if the administration of gadoxetate disodium (Gd-EOB-DTPA) significantly affects hepatic magnetic resonance elastography (MRE) measurements in the delayed hepatobiliary phase (DHBP). METHODS: A total of 47 patients (15 females, 32 males; age range 23-78 years, mean 54.28 years) were assigned to standard hepatic magnetic resonance imaging (MRI) with application of Gd-EOB-DTPA and hepatic MRE. MRE was performed before injection of Gd-EOB-DTPA and after 40-50 min in the DHBP. Liver stiffness values were obtained before and after contrast media application and differences between pre- and post-Gd-EOB-DTPA values were evaluated using a Bland-Altman plot and the Mann-Whitney-Wilcoxon test. In addition, the data were compared with regard to the resulting fibrosis classification. RESULTS: Mean hepatic stiffness for pre-Gd-EOB-DTPA measurements was 4.01 kPa and post-Gd-EOB-DTPA measurements yielded 3.95 kPa. We found a highly significant individual correlation between pre- and post-Gd-EOB-DTPA stiffness values (Pearson correlation coefficient of r = 0.95 (p < 0.001) with no significant difference between the two measurements (p =0.49)). Bland-Altman plot did not show a systematic effect for the difference between pre- and post-stiffness measurements (mean difference: 0.06 kPa, SD 0.81). Regarding the classification of fibrosis stages, the overall agreement was 87.23% and the intraclass correlation coefficient was 96.4%, indicating excellent agreement. CONCLUSIONS: Administration of Gd-EOB-DTPA does not significantly influence MRE stiffness measurements of the liver in the DHBP. Therefore, MRE can be performed in the DHBP. KEY POINTS: • MRE of the liver can reliably be performed in the delayed hepatobiliary phase. • Gd-EOB-DTPA does not significantly influence MRE stiffness measurements of the liver. • MRE performed in the delayed hepatobiliary-phase is reasonable in patients with reduced liver function.

[Adverse effects of immunotherapy : Clinical aspects, radiological and nuclear medicine results]. / Unerwünschte Wirkungen der Immuntherapie : Klinik, radiologische und nuklearmedizinische Befunde.

BACKGROUND: The increasing use of immunotherapy in oncology increases the need for radiologic evaluation of frequent and severe immune-related adverse events. OBJECTIVE: Determination of the incidence and manifestation of radiologic and nuclear medicine findings of immune-related adverse events. MATERIAL AND METHODS: Literature review of clinical and imaging findings of immune-related adverse events induced by the immune checkpoint inhibitors ipilimumab, nivolumab and pembrolizumab. Findings are illustrated with pictorial examples and contrasted to other relevant differential diagnoses. RESULTS: The most frequent imaging manifestations are colitis, hepatitis, pancreatitis, hypophysitis, pneumonitis, arthritis and sarcoid-like lymphadenopathy. Severe to life-threatening complications may result from colitis, pneumonitis and hypophysitis. A clear differentiation from other autoimmune diseases and discrimination of immune-related and infectious pulmonary findings can be very difficult and need close multidisciplinary collaboration. CONCLUSION: Knowledge of clinical and imaging findings of adverse events induced by immunotherapy is essential for timely and adequate therapeutic decisions. In addition to staging and follow-up imaging, identification and monitoring of immune-related adverse events adds to the radiologic responsibility in oncologic care.

Feasibility of Ultrasound-Guided Sacroiliac Joint Injections in Children Presenting with Sacroiliitis.

PURPOSE: To evaluate the feasibility and effectiveness of US-guided sacroiliac joint injection in the treatment of sacroiliitis in children. MATERIALS AND METHODS: This study was approved by the institutional review board and informed oral and written consent was obtained from the patients and their parents. In 13 patients (7 females and 6 males), 9 - 16 years (mean +/- std 11.39 +/-1.98), 18 sacroiliac joint (SI joint) injections were performed under US guidance. All patients suffered from severe sacroiliitis. US scanning was performed using a linear-array transducer operating at 5 - 18 MHz. Rating of the patients pain using a 0 - 10 dolorimetry scale on a visual analog score (VAS) was recorded before, immediately after and 3 months after injection to monitor severity and therapeutic response. RESULTS: Injection could be performed in all patients without complication and showed good response immediately and 3 months after the injection with a decrease of the VAS (from mean +/- std 9.44 +/- 1.097 to 3.89 +/- 3.82, p < 0.001 and to 0.56 +/- 1.097, p < 0.05, respectively). CONCLUSION: US-guided SI joint injection was feasible in all children, relatively quick and easy to perform and appeared effective in the treatment of children with sacroiliitis.

Automated two-point dixon screening for the evaluation of hepatic steatosis and siderosis: comparison with R2-relaxometry and chemical shift-based sequences.

OBJECTIVES: To evaluate the automated two-point Dixon screening sequence for the detection and estimated quantification of hepatic iron and fat compared with standard sequences as a reference. METHODS: One hundred and two patients with suspected diffuse liver disease were included in this prospective study. The following MRI protocol was used: 3D-T1-weighted opposed- and in-phase gradient echo with two-point Dixon reconstruction and dual-ratio signal discrimination algorithm ("screening" sequence); fat-saturated, multi-gradient-echo sequence with 12 echoes; gradient-echo T1 FLASH opposed- and in-phase. Bland-Altman plots were generated and correlation coefficients were calculated to compare the sequences. RESULTS: The screening sequence diagnosed fat in 33, iron in 35 and a combination of both in 4 patients. Correlation between R2* values of the screening sequence and the standard relaxometry was excellent (r = 0.988). A slightly lower correlation (r = 0.978) was found between the fat fraction of the screening sequence and the standard sequence. Bland-Altman revealed systematically lower R2* values obtained from the screening sequence and higher fat fraction values obtained with the standard sequence with a rather high variability in agreement. CONCLUSIONS: The screening sequence is a promising method with fast diagnosis of the predominant liver disease. It is capable of estimating the amount of hepatic fat and iron comparable to standard methods. KEY POINTS: • MRI plays a major role in the clarification of diffuse liver disease. • The screening sequence was introduced for the assessment of diffuse liver disease. • It is a fast and automated algorithm for the evaluation of hepatic iron and fat. • It is capable of estimating the amount of hepatic fat and iron.

Sonoelastographic Findings of Carpal Tunnel Injection.

PURPOSE: The objectives of this study were to compare sonoelastographic color findings of the perineural area between carpal tunnel syndrome patients and healthy volunteers, and to analyze elastographic findings in that area before and immediately after intracarpal tunnel injection in carpal tunnel syndrome patients. MATERIALS AND METHODS: We studied both hands of 15 healthy volunteers (7 men, 8 women; mean age: 60.1 years, range: 41 - 88 years) and 72 hands from 70 patients with symptomatic carpal tunnel syndrome (24 men, 46 women; mean age: 54.2 years, range: 24 - 83 years). Sonoelastographic color distribution was assessed in the perineural area between the median nerve and adjacent flexor tendons. The color elastograms were graded using the following system: Grade 1 as red (softest), grade 2 as yellow (soft), grade 3 as green (hard), grade 4 as blue (hardest). The patients were treated with corticosteroid injection and were reassessed with sonoelastography immediately after the injection. RESULTS: The median color grading in the perineural area of carpal tunnel syndrome patients was grade 3 (3.1 ±â€Š0.3, mean ±â€Š95 % Cl), which was stiffer than that of healthy volunteers (grade 1, 1.9 ±â€Š0.4) (p < 0.0001). Immediately after injection, the diffusion of the injected fluid was observed as having a softer appearance (grade 1, 1.4 ±â€Š0.2) (p < 0.0001). CONCLUSION: The perineural area surrounding the median nerve in carpal tunnel syndrome patients was stiffer than that in healthy volunteers. Diffusion of the injected fluid in the carpal tunnel was seen as a softer finding after injection in real time using sonoelastography.

[Stereotaxy and robotics for ablation - toy or tool?]. / Stereotaxie und Robotik zur Ablation - Spielzeug oder Werkzeug?

CLINICAL AND METHODOLOGICAL ISSUES: Ablative technologies allow local curative tumor treatment by thermal tissue damage. An important prerequisite is the coverage of all tumor cells. Tumor size is the most important limiting factor. STANDARD RADIOLOGICAL METHODS: The drawbacks of conventional computed tomography/ultrasound/magnetic resonance imaging (CT/US/MRI) guided radiofrequency ablation (RFA) are the absence of planning software, imprecise probe placement, imprecise control of probe placement and the ablation zone as well as the lack of reliability and reproducibility. METHODOLOGICAL INNOVATIONS: Stereotactic and robot-assisted systems allow planning of multiple probe positions based on CT/MRI and positron emission tomography (PET) planning data. The probes can be precisely placed according to the coordinates of the image datasets. PERFORMANCE: The 1 and 3 year survival rates after stereotactic RFA (SRFA) of cholangiocellular carcinoma were 91% and 70% respectively and the median overall survival was 60 months. After SRFA of 189 colorectal liver metastases in 63 patients there was no significant difference in local recurrence rates between tumors < 3 cm (17.7%), 3-5 cm (11.1%) and > 5 cm (17.4%). The median overall survival was 33.2 months and the 1, 3, and 5 year overall survival rates after SRFA in patients with resectable colorectal cancer were 92%, 66% and 48%, respectively. ACHIEVEMENTS: In our opinion the excellent and, to a large extent user-independent results justify the increased efforts in time and costs especially for the treatment of patients with large and irregular tumors. PRACTICAL RECOMMENDATIONS: Stereotaxy and robotics are valuable tools for effective tumor ablation especially of large tumors and are likely to gain in importance in the next few years.

[Radiological imaging of osteoarthritis of the knee]. / Radiologische Bildgebung der Kniegelenkarthrose.

CLINICAL/METHODICAL ISSUE: Osteoarthritis is the most common degenerative age-related joint disease leading to typical degradation of articular cartilage with severe pain and limitation of joint motion. STANDARD RADIOLOGICAL METHODS: Although knee radiographs are widely considered as the gold standard for the assessment of knee osteoarthritis in clinical and scientific settings they increasingly have significant limitations in situations when resolution and assessment of cartilage is required. METHODICAL INNOVATIONS: Analysis of osteoarthritis of the knee with conventional x-ray is associated with many technical limitations and is increasingly being replaced by high-quality assessment using magnetic resonance imaging (MRI) or sonography both in the clinical routine and scientific studies. PERFORMANCE: Novel imaging modalities such as MRI or ultrasound enable in vivo visualization of the quality of the cartilaginous structure and bone as well as all articular and periarticular tissue. Therefore, the limitations of radiographs in assessment of knee osteoarthritis could be overcome by these techniques. This review article aims to provide insights into the most important radiological features of knee osteoarthritis and systematic visualization with different imaging approaches. PRACTICAL RECOMMENDATIONS: The demographic development in western industrialized countries predicts an increase of ageing-related osteoarthritis of the knee for the next decades. A systematic radiological evaluation of patients with knee osteoarthritis includes the assessment of the periarticular soft tissue, cartilaginous thickness, cartilage volume, possible cartilage defects, the macromodular network of hyaline cartilage, bone marrow edema, menisci and articular ligaments. Modern imaging modalities, such as MRI and sonography allow the limitations of conventional radiography to be overcome and to visualize the knee structures in great detail to quantitatively assess the severity of knee osteoarthritis.

[Focal nodular hyperplasia in a 12-year-old boy: case report and considerations]. / Fokale noduläre Hyperplasie bei einem 12-jährigen Jungen: Fallbericht und Themenbetrachtung.

BACKGROUND: Focal nodular hyperplasia (FNH) is a benign hepatic tumor of unknown origin. It is only observed rarely in children (approximately 1-2% of all pediatric liver tumors). CASE REPORT: A 12-year-old boy who suffered from infectious mononucleosis with liver involvement and hepatomegaly underwent a sonographic scan of the liver at an external hospital 3 months after the infection disappeared which revealed a tumor of the left hepatic lobule. Subsequent further examination (abdominal CT and MRT scans) confirmed the diagnosis of a highly vascularized mass about 10 cm in diameter, suspicious for FNH. Due to the high vascularization no biopsy was performed. A preoperative angiographic coiling and complete surgical resection was carried out because of the size and morphologic uncertainty. The diagnosis of FNH was confirmed by histological examination. The annual sonographic examination at follow-up has been uneventful for a 4-year period. CONCLUSIONS: Due to the rarity the diagnosis of FNH in children can be difficult leading to differential diagnostic problems. Due to the risk of bleeding in larger size tumors a biopsy is a point of controversy. Complete resection and histopathological examination of FNHs in childhood is a mandatory therapeutic option, which may be indicated in large tumors or, as in the present case tumors of uncertain biological behaviour.

US-guided therapy of calcific tendinopathy: clinical and radiological outcome assessment in shoulder and non-shoulder tendons.

PURPOSE: To analyze the effectiveness and complication rate of ultrasound (US)-guided perforation and lavage using a two-needle technique with 16 - 18 G needles in the treatment of patients with calcific tendinopathy in the shoulder, elbow, hip, and knee by radiological and clinical follow-up. MATERIALS AND METHODS: A retrospective chart review was performed and 40 patients (13 male, 27 female; mean age, 53.5 years; range 24 -74 years) were identified as having received US-guided perforation and lavage due to symptomatic calcific tendinopathy of the rotator cuff tendons, triceps, extensor and flexor tendons at the elbow, rectus femoris tendon and patellar tendons. The radiographic outcome was assessed by comparison of the size and quality of the calcification before and 6 weeks after the procedure. On US images, the quality of the acoustic shadow was assessed, together with other alterations of the tendon and surrounding tissue. Patients were interviewed by telephone to assess the clinical outcome regarding pre-treatment and post-treatment pain and tendon function. RESULTS: 34 shoulder tendons and 6 non-shoulder tendons were identified. The mean calcium reduction was 39.9 mm(2) (range, 0 - 215; p < 0.001), while 80 % of patient showed a resolution of more than 60 % resulting in good clinical improvement. A very low complication rate was found (1 partial tear). CONCLUSION: The US-guided perforation and lavage technique is an effective and safe treatment for rotator cuff calcifications as well as for other body tendons. Although the two-needle technique and large needles were used in this study, a very low complication rate was detected.

Contrast-enhanced ultrasonography for the detection of joint vascularity in arthritis--subjective grading versus computer-aided objective quantification.

PURPOSE: To compare joint inflammation assessment using subjective grading of power Doppler ultrasonography (PDUS) and contrast-enhanced ultrasonography (CEUS) versus computer-aided objective CEUS quantification. MATERIALS AND METHODS: 37 joints of 28 patients with arthritis of different etiologies underwent B-mode ultrasonography, PDUS, and CEUS using a second-generation contrast agent. Synovial thickness, extent of vascularized pannus and intensity of vascularization were included in a 4-point PDUS and CEUS grading system. Subjective CEUS and PDUS scores were compared to computer-aided objective CEUS quantification using Qontrast® software for the calculation of the signal intensity (SI) and the ratio of SI for contrast enhancement. RESULTS: The interobserver agreement for subjective scoring was good to excellent (κ = 0.8 - 1.0; P < 0.0001). Computer-aided objective CEUS quantification correlated statistically significantly with subjective CEUS (P < 0.001) and PDUS grading (P < 0.05). The Qontrast® SI ratio correlated with subjective CEUS (P < 0.02) and PDUS grading (P < 0.03). Clinical activity did not correlate with vascularity or synovial thickening (P = N. S.) and no correlation between synovial thickening and vascularity extent could be found, neither using PDUS nor CEUS (P = N. S.). CONCLUSION: Both subjective CEUS grading and objective CEUS quantification are valuable for assessing joint vascularity in arthritis and computer-aided CEUS quantification may be a suitable objective tool for therapy follow-up in arthritis.

[New ultrasound technologies for the diagnostics of prostate cancer]. / Neue Ultraschalltechnologien für die Diagnostik des Prostatakarzinoms.

CLINICAL/METHODOLOGICAL ISSUE: Prostate cancer is the most common cancer in men. The diagnosis is based on prostate-specific antigen (PSA), digital rectal examination (DRE) and transrectal ultrasound (TRUS) guided biopsy. These techniques have considerable limitations, which result in unnecessary biopsies. Furthermore the biopsies are associated with morbidity and costs. STANDARD RADIOLOGICAL METHODS: Standard gray-scale ultrasound has a low sensitivity and specificity for prostate cancer detection. METHODOLOGICAL INNOVATIONS: New ultrasound technologies, including color- and power Doppler ultrasound, contrast enhanced US and real-time sonoelastography have shown to improve prostate cancer diagnosis. PERFORMANCE: Contrast-enhanced ultrasound has shown a sensitivity of 100% (95% CI, 95%), a negative predictive value (NPV) of 99.8% and a positive predictive value (PPV) of 88.8% for prostate cancer detection. Real-time sonoelastography has shown a sensitivity of 86%, a specificity of 81% and NPV of 91% for prostate cancer diagnosis. ACHIEVEMENTS: Most studies show that these new ultrasound modalities demonstrate a 1.5 to 2.5 times higher detection of prostate cancer per biopsy specimen compared with systematic biopsy. Multicenter studies results are at present lacking but are, however ongoing. PRACTICAL RECOMMENDATIONS: In patients with suspected prostate cancer (elevated PSA, suspicious DRE) these new ultrasound techniques should be used. These techniques can detect prostate cancer and allow a targeted biopsy approach.

Navigated open, laparoscopic, and percutaneous liver surgery.

Resection and thermal ablation procedures are frequently used for the treatment of primary and secondary liver tumors. Various tools for the virtual planning of liver resections and ablation are available and some of them are already used clinically. Resection planes and ablation volumes can be optimized for sufficient safety margins while preserving a maximal amount of functional liver tissue. Connecting the pre-operative planning with intraoperative guidance based on the 3D imaging data would be desirable. Interactive image guided surgery enables visualization of the actual spatial location of the surgical instrument on preoperatively acquired images in real time. However, extensive soft tissue deformations during open and laparoscopic surgical and ablative procedures may occur, causing unacceptable inaccuracies. The current focus of research is the adaptation of the preoperative virtual planning models to surgery by using intraoperative imaging and biomechanical models. In contrast to open and laparoscopic surgical procedures percutaneous punctures can be performed with high accuracy under stereotactic conditions. Important prerequisites include patient immobilization, respiratory triggering and intraoperative imaging. Due to the high accuracy of probe positioning the virtual preoperative ablation plan can be precisely transferred into the real patient. A total of 350 patients with primary and secondary liver tumors have already successfully been treated with stereotactic radiofrequency ablation (SRFA). Due to its low complication rates and similar local recurrence and survival rates as compared to conventional surgery SRFA is an attractive alternative for the treatment for primary and secondary liver tumors.

Albumin-based nanoparticles as magnetic resonance contrast agents: II. Physicochemical characterisation of purified and standardised nanoparticles.

We are developing a nanoparticulate histochemical reagent designed for histochemistry in living animals (molecular imaging), which should finally be useful in clinical imaging applications. The iterative development procedure employed involves conceptual design of the reagent, synthesis and testing of the reagent, then redesign based on data from the testing; each cycle of testing and development generates a new generation of nanoparticles, and this report describes the synthesis and testing of the third generation. The nanoparticles are based on human serum albumin and the imaging modality selected is magnetic resonance imaging (MRI). Testing the second particle generation with newly introduced techniques revealed the presence of impurities in the final product, therefore we replaced dialysis with diafiltration. We introduced further testing methods including thin layer chromatography, arsenazo III as chromogenic assay for gadolinium, and several versions of polyacrylamide gel electrophoresis, for physicochemical characterisation of the nanoparticles and intermediate synthesis compounds. The high grade of chemical purity achieved by combined application of these methodologies allowed standardised particle sizes to be achieved (low dispersities), and accurate measurement of critical physicochemical parameters influencing particle size and imaging properties. Regression plots confirmed the high purity and standardisation. The good degree of quantitative physicochemical characterisation aided our understanding of the nanoparticles and allowed a conceptual model of them to be prepared. Toxicological screening demonstrated the extremely low toxicity of the particles. The high magnetic resonance relaxivities and enhanced mechanical stability of the particles make them an excellent platform for the further development of MRI molecular imaging.

Albumin-based nanoparticles as magnetic resonance contrast agents: I. Concept, first syntheses and characterisation.

To develop a platform for molecular magnetic resonance imaging, we prepared gadolinium-bearing albumin-polylactic acid nanoparticles in the size range 20-40 nm diameter. Iterative cycles of design and testing upscaled the synthesis procedures to gram amounts for physicochemical characterisation and for pharmacokinetic testing. Morphological analyses showed that the nanoparticles were spheroidal with rough surfaces. Particle sizes were measured by direct transmission electron microscopical measurements from negatively contrasted preparations, and by use of photon correlation spectroscopy; the two methods each documented nanoparticle sizes less than 100 nm and generally 10-40 nm diameter, though with significant intrabatch and interbatch variability. The particles' charge sufficed to hold them in suspension. HSA retained its tertiary structure in the particles. The nanoparticles were stable against turbulent flow conditions and against heat, though not against detergents. MRI imaging of liquid columns was possible at nanoparticle concentrations below 10 mg/ml. The particles were non-cytotoxic, non-thrombogenic and non-immunogenic in a range of assay systems developed for toxicity testing of nanoparticles. They were micellar prior to lyophilisation, but loosely structured aggregated masses after lyophilisation and subsequent resuspension. These nanoparticles provide a platform for further development, based on non-toxic materials of low immunogenicity already in clinical use, not expensive, and synthesized using methods which can be upscaled for industrial production.

Real-time sonoelastography: findings in patients with symptomatic achilles tendons and comparison to healthy volunteers.

PURPOSE: Real-time sonoelastography (SE), a newly introduced ultrasound technique, has already shown conclusive results in breast, prostate, and thyroid tumor diagnostics. This study investigated the performance of SE for the differentiation of Achilles tendon alterations of tendinopathy compared to clinical examination and conventional ultrasound (US). MATERIALS AND METHODS: Achilles tendons in 25 consecutive patients with chronic Achilles tendinopathy and 25 healthy volunteers were examined clinically by US and by SE. RESULTS: In the healthy volunteers, SE showed the tendon to be hard (93 %), while distinct softening was found in 57 % of the patients. SE showed more frequent involvement of the distal (64 %) and middle third (80 %) than the proximal third (28 %) of the Achilles tendon. Using SE a mean sensitivity of 94 %, specificity of 99 %, and accuracy of 97 % were found when clinical examination was used as the reference standard. The correlation to US was 0.89. Mild softening was found in 7 % of the healthy volunteers and in 11 % of the patients. CONCLUSION: Our results emphasize that only distinct softening of Achilles tendons is comparable to clinical examination and US findings. However, mild softening might be explained by very early changes in tissue elasticity in the case of Achilles tendinopathy, which should be assessed in follow-up studies.

Patient dose in interventional radiology: a European survey.

Patient doses for a few common fluoroscopy-guided procedures in interventional radiology (IR) (excluding cardiology) were collected from a few radiological departments in 13 European countries. The major aim was to evaluate patient doses for the basis of the reference levels. In total, data for 20 procedures for about 1300 patients were collected. There were many-fold variations in the number of IR equipment and procedures per population, in the entrance dose rates, and in the patient dose data (total dose area product or DAP, fluoroscopy time and number of frames). There was no clear correlation between the total DAP and entrance dose rate, or between the total DAP and fluoroscopy time, indicating that a number of parameters affect the differences. Because of the limited number of patients, preliminary reference levels were proposed only for a few procedures. There is a need to improve the optimisation of IR procedures and their definitions and grouping, in order to account for their different complexities.

Evaluation of an accelerated 3D SPACE sequence with compressed sensing and free-stop scan mode for imaging of the knee.

PURPOSE: To prospectively evaluate a prototypical 3D turbo-spin-echo proton-density-weighted sequence with compressed sensing and free-stop scan mode for preventing motion artefacts (3D-PD-CS-SPACE free-stop) for knee imaging in a clinical setting. METHODS AND MATERIALS: 80 patients underwent 3T magnetic resonance imaging (MRI) of the knee with our 2D routine protocol and with 3D-PD-CS-SPACE free-stop. In case of a scan-stop caused by motion (images are calculated nevertheless) the sequence was repeated without free-stop mode. All scans were evaluated by 2 radiologists concerning image quality of the 3D-PD-CS-SPACE (with and without free-stop). Important knee structures were further assessed in a lesion based analysis and compared to our reference 2D-PD-fs sequences. RESULTS: Image quality of the 3D-PD-CS-SPACE free-stop was found optimal in 47/80, slightly compromised in 21/80, moderately in 10/80 and severely in 2/80. In 29/80, the free-stop scan mode stopped the 3D-PD-CS-SPACE due to subject motion with a slight increase of image quality at longer effective acquisition times. Compared to the 3D-PD-CS-SPACE with free-stop, the image quality of the acquired 3D-PD-CS-SPACE without free-stop was found equal in 6/29, slightly improved in 13/29, improved with equal contours in 8/29, and improved with sharper contours in 2/29. The lesion based analysis showed a high agreement between the results from the 3D-PD-CS-SPACE free-stop and our 2D-PD-fs routine protocol (overall agreement 96.25%-100%, Cohen's Kappa 0.883-1, p < 0.001). CONCLUSION: 3D-PD-CS-SPACE free-stop is a reliable alternative for standard 2D-PD-fs protocols with acceptable acquisition times.

Integrating interventional oncology in the treatment of liver tumors.

BACKGROUND: Percutaneous ablation techniques offer a vast armamentarium for local, minimally invasive treatment of liver tumors, nowadays representing an established therapeutic option, which is integrated in treatment algorithms, especially for non-resectable liver tumors. The results of ablative treatment compare very well to surgical treatment in liver lesions, and confirm that these techniques are a valuable option for bridging for transplantation. Different techniques have been established to perform tumor ablation, and the feasibility varies according to the procedure and technical skills of the operator, depending on the size and location of the liver lesion. In recent years, stereotactic multi-needle techniques using 3D trajectory planning, general anesthesia, and tube disconnection during needle placement have had a strong impact on the application range of ablation for liver tumors. CONCLUSION: It is well known that creating a sufficient ablation margin and overlapping ablation zones is one key issue to enable ablation of large liver lesions with tumor-free margins (A0 ablation in analogy to R0 resection). Image fusion during treatment and follow-up assure highly accurate staging procedures and interventional planning. NOVEL ASPECTS: Review on the standards in ablation techniques for the treatment of liver tumors. Update on different ablation techniques, indications, and contraindications for percutaneous liver tumor treatment. Summary of recently published reports on liver tumor ablation.