MRI analysis of simple and aneurysmal bone cysts in the proximal humerus: what actually matters in clinical routine.

OBJECTIVE: To evaluate magnetic resonance imaging (MRI) characteristics of simple and aneurysmal bone cysts (SBC/ABC) of the proximal humerus and the intermittent difficulty in the imaging differentiation between the two in daily clinical routine. MATERIALS AND METHODS: MR images of 26 patients with suspected SBC/ABC in the proximal humerus were retrospectively assessed by two independent radiologists blinded to the final histological result. Based on a standard MRI protocol, different morphologic features and signal intensities of the lesion on non-enhanced and enhanced sequences were documented. The radiological diagnosis was correlated with histology. RESULTS: Eighteen patients had the image-based diagnosis of an SBC, yet the histology confirmed only 12, the residual 6 were identified as an ABC, despite the imaging criteria corresponding unambiguously to the former. One of the main reasons was the unicameral morphology of lesions, found in 9/14 (64.3%) cases of all ABCs, i.e., in 19/26 cases in total. Therefore, the sensitivity of the radiological diagnosis was moderate (57.14%), yet specificity very high (100%). In total, 69.2% (18/26) presented with a pathological fracture at admission, which correlated strongly with both circumferential (MCC = 0.65, p = 0.01) and septal (MCC = 0.42, p = 0.06) enhancement patterns. Circumferential enhancement was also found to correlate strongly with the histological diagnosis, being recognized in all cases of ABC (MCC = 0.44, p = 0.06). CONCLUSION: MRI characteristics of ABCs/SBCs in the proximal humerus are indifferent and ABCs may morphologically present as SBCs. Radiologists should be aware of the different, often confusing presentation of both entities in daily clinical routine.

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.

Acute Gouty Knee Arthritis: Ultrasound Findings Compared With Dual-Energy CT Findings.

OBJECTIVE: The purpose of this study was to compare findings of ultrasound (US) with dual-energy CT (DECT) findings in patients presenting with suspected gouty knee arthritis. SUBJECTS AND METHODS: This prospective study included 65 patients (52 men and 13 women; median age, 61.7 years [range, 38-87 years]) with an initial clinical diagnosis of acute gouty knee arthritis who underwent DECT performed using a 128-MDCT scanner and US performed using a 5-18-MHz transducer. Both intra- and extraarticular findings obtained using each modality were tabulated. RESULTS: DECT identified gout as the final diagnosis for 52 of 65 patients (80.0%). An alternative diagnosis was confirmed for the remaining 13 patients. US detected gout in 31 of 52 patients (sensitivity, 59.6%) and produced findings negative for gout in seven of 13 patients (specificity, 53.8%). The double contour sign on US was positive for gout in 23 of 52 patients (44.2%) and negative in 12 of 13 patients (92.3%). Extraarticular urate deposition was identified by DECT in 44 of 52 patients, compared with identification by US in 11 of 52 patients (p < 0.001). CONCLUSION: The sensitivity of US for the diagnosis of gouty knee arthritis is limited, particularly with respect to extraarticular urate deposition. The double contour sign is the single most valuable sign for the assessment of gouty knee arthritis by US.

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.

Carpal tunnel syndrome assessment with diffusion tensor imaging: Value of fractional anisotropy and apparent diffusion coefficient.

OBJECTIVES: To quantitatively assess carpal tunnel syndrome (CTS) with DTI by evaluating two approaches to determine cut-off values. METHODS: In forty patients with CTS diagnosis confirmed by nerve conduction studies (NCs) and 14 healthy subjects (mean age 58.54 and 57.8 years), cross-sectional area (CSA), apparent diffusion coefficient (ADC) and fractional anisotropy (FA) at single and multiple levels with intraobserver agreement were evaluated. RESULTS: Maximum and mean CSA and FA showed significant differences between healthy subjects and patients (12.85 mm2 vs. 28.18 mm2, p < 0.001, and 0.613 vs. 0.524, p=0.007, respectively) (10.12 mm2 vs. 19.9 mm2, p<0.001 and 0.617 vs. 0.54, p=0.003, respectively), but not maximum and mean ADC (p > 0.05). For cut-off values, mean and maximum CSA showed the same sensitivity and specificity (93.3 %). However, mean FA showed better sensitivity than maximum FA (82.6 % vs. 73.9 %), but lower specificity (66.7 % vs. 80 %), and significant correlation for maximum CSA, 97 % (p < 0.01), with good correlation for maximum ADC and FA, 84.5 % (p < 0.01) and 62 % (p=0.056), respectively. CONCLUSIONS: CSA and FA showed significant differences between healthy subjects and patients. Single measurement at maximum CSA is suitable for FA determination. Key Points • DTI showed that FA is stronger than ADC for CTS diagnosis. • Single- and multiple-level approaches were compared to determine FA and ADC. • Single-level evaluation at the thickest MN cross-sectional area is sufficient.

R2*-relaxometry of the pancreas in patients with human hemochromatosis protein associated hereditary hemochromatosis.

PURPOSE: To evaluate pancreatic iron in patients with human hemochromatosis protein associated hereditary hemochromatosis (HHC) using R2* relaxometry. MATERIALS AND METHODS: 81 patients (58 male, 23 female; median age 49.5, range 10-81 years) with HHC were retrospectively studied. All underwent 1.5T magnetic resonance imaging (MRI) of the abdomen. A fat-saturated multi-gradient echo sequence with 12 echoes (TR=200ms; TE-initial 0.99ms; Delta-TE 1.41ms; 12 echoes; flip-angle: 20°) was used for the R2* quantification of the liver and the pancreas. Parameter maps were analyzed using regions of interest (3 in the liver and 2 in the pancreas) and R2* values were correlated. RESULTS: 59/81 patients had a liver R2*≥70 1/s of which 10/59 patients had a pancreas R2*≥50 1/s. No patient presented with a liver R2*<70 1/s and pancreas R2*≥50 1/s. All patients with pancreas R2* values≥50 1/s had liver R2* values≥70 1/s. ROC analysis resulted in a threshold of 209.4 1/s for liver R2* values to identify HFE positive patients with pancreas R2* values≥50 1/s with a median specificity of 78.87% and a median sensitivity of 90%. CONCLUSION: In patients with HHC R2* relaxometry of the pancreas should be performed when liver iron overload is present and can be omitted in cases with no sign of hepatic iron.

R2* relaxometry for the quantification of hepatic iron overload: biopsy-based calibration and comparison with the literature.

PURPOSE: We compared the calibration of hepatic iron based on R2* relaxometry and liver biopsy with similar studies that have already been published to investigate the transferability of published calibration curves. MATERIALS AND METHODS: 17 patients with clinically suspected hepatic iron overload (HIO) were enrolled. All patients underwent liver biopsy and MRI of the liver using a multi-echo gradient echo sequence (TR = 200 ms; TE-initial 0.99 ms; Delta-TE 1.41 ms; 12 echos; flip-angle: 20 °). R2* parameter maps were analyzed using manually placed regions of interest and R2* values were correlated with liver iron concentration (LIC) obtained from liver biopsy. In addition, the results of our study were compared with 6 similar, already published studies. RESULTS: A linear relationship between R2* and LIC was found. Regression analysis yielded a correlation coefficient of 0.926, a slope of 0.024 (s mg/g) [95 % CI 0.013 - 0.024] and an intercept of 0.277 (mg/g) [95 % CI -0.328 - 2.49]. We found a significant correlation between the calibration curves obtained from our study in comparison to 3/6 similar studies. The other 3 studies used a different reference standard or sequence parameters which lead to a significant difference for slope, intercept or both in comparison to our data. CONCLUSION: Calibration curves from published studies that are based on a correlation of liver biopsy and R2* can be used for the estimation of liver iron concentration, although different scanning parameters and post-processing protocols were used. Low initial TEs might be a prerequisite for pooling data for liver iron quantification. KEY POINTS: • Calibration curves from different studies can be used for liver iron quantification• For that purpose calibration curves from published studies should be based on liver biopsy• Low initial TEs might be a prerequisite for pooling data for liver iron quantification.

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.

Association of aortic stiffness with biomarkers of myocardial wall stress after myocardial infarction.

BACKGROUND: Aortic pulse wave velocity (PWV) was linked to LV-geometry and -function in patients with kidney disease and non-ischemic cardiomyopathy. The role of aortic compliance after acute STEMI is so far unknown. In the present study, we prospectively investigated the relationship of increased aortic stiffness with biomarkers of myocardial wall stress 4 months after STEMI. METHODS: 48 STEMI patients who were reperfused by primary coronary angioplasty underwent cardiovascular magnetic resonance (CMR) at baseline and at 4-month follow-up. The CMR protocol comprised cine-CMR as well as gadolinium contrast-enhanced CMR. Aortic PWV was determined by velocity-encoded, phase-contrast CMR. Blood samples were routinely drawn at baseline and follow-up to determine N-terminal pro-B-type natriuretic peptide (NT-proBNP). In a subgroup of patients, mid-regional pro-adrenomedullin (MR-proADM) and mid-regional pro-A-type natriuretic peptide (MR-proANP) levels were determined. RESULTS: Patients with a PWV above median (>7.0m/s) had significantly higher NT-proBNP, MR-proADM and MR-proANP concentrations at 4-month follow-up than patients with a PWV below median (all p<0.02). PWV showed moderate to good correlation with NT-proBNP, MR-proAMD and MR-proANP levels 4 months after STEMI (all p<0.05). Multivariate analysis revealed PWV, beside myocardial infarct size, as an independent predictor of 4-month NT-proBNP levels after correction for age, creatinine and LV ejection fraction (model r: 0.781, p<0.001). CONCLUSION: Aortic stiffness is directly associated with biomarkers of myocardial wall stress 4 months after reperfused STEMI, suggesting a role for aortic stiffness in chronic LV-remodelling.

Transperineal ultrasonography as a complementary diagnostic tool in identifying acute perianal sepsis.

BACKGROUND: Successful anal fistula care in complex cases can be assisted by specialized imaging which accurately defines the site of the internal fistula opening and the fistula type. There are currently limited data concerning the clinical indications for and accuracy of transperineal ultrasound (TP-US) in acute perianal sepsis. The aims of this study were to compare the anatomical interpretation of TP-US images with magnetic resonance imaging (MRI) and surgical findings in an unselected patient cohort presenting with acute perianal sepsis. METHODS: Sixty-seven consecutive patients with acute anorectal sepsis referred from the surgical department were examined using TP-US and Gadolinium-enhanced MRI with both examiners blinded to the surgical results. Fistulae were categorized by the Parks' classification of fistula type. RESULTS: Thirty-six abscesses were detected by MRI, 38 by TP-US and 30 by surgical examination. Operatively discordant cases showed only ischiorectal panniculitis. TP-US was more accurate in the diagnosis of superficial sepsis and MRI in the diagnosis of deep-seated perirectal infection. TP-US and MRI show concordance with operative findings in fistula diagnosis with a tendency for TP-US to overdiagnose trans-sphincteric fistulae and MRI to over diagnose extra-sphincteric fistulae. Comparison of TP-US with MRI showed good agreement for perianal abscess diagnosis (τ = 0.82) and for fistula diagnosis (τ = 0.68). For fistulae, TP-US showed moderate agreement with surgery (τ = 0.43) with only fair agreement between MRI and surgery (τ = 0.29). CONCLUSIONS: Transperineal ultrasound complements other imaging modalities in the anatomical diagnosis of acute perianal abscesses and fistulae. It has specific advantages over other techniques and is accurate in the detection of superficially located perirectal sepsis showing concordance with MRI and surgical findings.

Different metabolic responses during incremental exercise assessed by localized 31P MRS in sprint and endurance athletes and untrained individuals.

Until recently, assessment of muscle metabolism was only possible by invasive sampling. 31P magnetic resonance spectroscopy (31P MRS) offers a way to study muscle metabolism non-invasively. The aim of the present study was to use spatially-resolved 31P MRS to assess the metabolism of the quadriceps muscle in sprint-trained, endurance-trained and untrained individuals during exercise and recovery. 5 sprint-trained (STA), 5 endurance-trained (ETA) and 7 untrained individuals (UTI) completed one unlocalized 31P MRS session to measure phosphocreatine (PCr) recovery, and a second session in which spatially-resolved 31P MR spectra were obtained. PCr recovery time constant (τ) was significantly longer in STA (50±17 s) and UTI (41±9 s) than in ETA (30±4 s), (P<0.05). PCr changes during exercise differed between the groups, but were uniform across the different components of the quadriceps within each group. pH during recovery was higher for the ETA than for the UTI (P<0.05) and also higher than for the STA (P<0.01). Muscle volume was greater in STA than in UTI (P<0.05) but not different from ETA. Dynamic 31P MRS revealed considerable differences among endurance and sprint athletes and untrained people. This non-invasive method offers a way to quantify differences between individual muscles and muscle components in athletes compared to untrained individuals.

Evaluation of MR imaging with T1 and T2* mapping for the determination of hepatic iron overload.

OBJECTIVES: To evaluate MRI using T1 and T2* mapping sequences in patients with suspected hepatic iron overload (HIO). METHODS: Twenty-five consecutive patients with clinically suspected HIO were retrospectively studied. All underwent MRI and liver biopsy. For the quantification of liver T2* values we used a fat-saturated multi-echo gradient echo sequence with 12 echoes (TR = 200 ms, TE = 0.99 ms + n × 1.41 ms, flip angle 20°). T1 values were obtained using a fast T1 mapping sequence based on an inversion recovery snapshot FLASH sequence. Parameter maps were analysed using regions of interest. RESULTS: ROC analysis calculated cut-off points at 10.07 ms and 15.47 ms for T2* in the determination of HIO with accuracy 88 %/88 %, sensitivity 84 %/89.5 % and specificity 100 %/83 %. MRI correctly classified 20 patients (80 %). All patients with HIO only had decreased T1 and T2* relaxation times. There was a significant difference in T1 between patients with HIO only and patients with HIO and steatohepatitis (P = 0.018). CONCLUSIONS: MRI-based T2* relaxation diagnoses HIO very accurately, even at low iron concentrations. Important additional information may be obtained by the combination of T1 and T2* mapping. It is a rapid, non-invasive, accurate and reproducible technique for validating the evidence of even low hepatic iron concentrations. KEY POINTS: • Hepatic iron overload causes fibrosis, cirrhosis and increases hepatocellular carcinoma risk. • MRI detects iron because of the field heterogeneity generated by haemosiderin. • T2* relaxation is very accurate in diagnosing hepatic iron overload. • Additional information may be obtained by T1 and T2* mapping.

Thiolated polyacrylic acid-modified iron oxide nanoparticles for in vitro labeling and MRI of stem cells.

PURPOSE: The purpose of this study was to develop and characterize new surface-modified iron oxide nanoparticles demonstrating the efficiency to be internalized by human endothelial progenitor cells (EPCs) from umbilical cord blood. METHODS: Iron oxide nanoparticles were coated with polyacrylic acid-cysteine (PAA-Cys) by either in situ precipitation or postsynthesis. The nanoparticles were characterized by X-ray powder diffraction. EPCs were labeled with PAA-Cys-modified iron oxide nanoparticles or with uncoated nanoparticles. The relaxivity of uncoated and coated iron oxide nanoparticles as well as EPCs labeled with PAA-Cys-modified iron oxide were determined. RESULTS: Addition of PAA-Cys increased the particle size from 10.4 to 144 and 197 nm, respectively. The X-ray powder diffraction pattern revealed that the particles consist of Fe(3)O(4) with a spinal structure. Postsynthesis coated particles showed a cellular uptake of 85% and 15.26 pg iron/cell. For both types of particles the relaxivity ratio was at least 2-fold higher than that of the gold standard Resovist(®). CONCLUSION: The PAA-Cys coated iron oxide nanoparticles are a promising tool for labeling living cells such as stem cells for diagnostic and therapeutic application in cell-based therapies due to their high relaxivities and their easy uptake by cells.

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.

[Magnetic resonance imaging of radiofrequency current-induced coagulation zones in the ex vivo bovine liver]. / Magnetresonanztomografie von durch Radiofrequenzablation erzeugten Koagulationszonen in der Ex-vivo-Rinderleber.

PURPOSE: To compare different magnetic resonance imaging sequences for correct representation and discrimination between non-ablated, partially ablated, and completely ablated tissue after radiofrequency ablation (RFA) in the ex vivo, non-perfused bovine liver model. MRI is the method of choice for imaging of the induced coagulation zones ex vivo. However, the optimal imaging sequence has not been determined yet. MATERIALS AND METHODS: RFA, which is a method to locally destroy malignant cells with heat and which has been established for the treatment of non-resectable liver tumors, was applied to bovine livers. After the RF ablation procedure, the livers were sliced for visual inspection of the coagulation zones. As a result, non-ablated, partially ablated, and completely ablated tissues were distinguished. For the subsequent MR imaging, markers were used to indicate the borders of the different zones. For every imaging sequence the tissue representation at the site of these markers was classified as "exact", "overestimating", "underestimating" and "not determinable". Additionally, T 1, T 2, and proton density (PD) maps were measured. RESULTS: It was found that both T 1 and T 2 values gradually decrease from non-ablated to ablated tissue, with T 1 showing a stronger relative change compared to T 2. For PD no change was observed between non-ablated and partially ablated tissue and a clear decrease was detected for the completely ablated zone. CONCLUSION: Sequences with a strong PD influence resulted in the highest accuracy for discrimination between completely ablated and partially ablated tissue. The differences in image quality and contrast could be explained by the observed T 1, T 2 and PD changes.

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.