Circulating extracellular vesicles as biomarker for diagnosis, prognosis, and monitoring in glioblastoma patients.

BACKGROUND: Extracellular vesicles (EVs) obtained by noninvasive liquid biopsy from patient blood can serve as biomarkers. Here, we investigated the potential of circulating plasma EVs to serve as an indicator in the diagnosis, prognosis, and treatment response of glioblastoma patients. METHODS: Plasma samples were collected from glioblastoma patients at multiple timepoints before and after surgery. EV concentrations were measured by nanoparticle tracking analysis and imaging flow cytometry. Tumor burden and edema were quantified by 3D reconstruction. EVs and tumors were further monitored in glioma-bearing mice. RESULTS: Glioblastoma patients displayed a 5.5-fold increase in circulating EVs compared to healthy donors (P < .0001). Patients with higher EV levels had significantly shorter overall survival and progression-free survival than patients with lower levels, and the plasma EV concentration was an independent prognostic parameter for overall survival. EV levels correlated with the extent of peritumoral fluid-attenuated inversion recovery hyperintensity but not with the size of the contrast-enhancing tumor, and similar findings were obtained in mice. Postoperatively, EV concentrations decreased rapidly back to normal levels, and the magnitude of the decline was associated with the extent of tumor resection. EV levels remained low during stable disease, but increased again upon tumor recurrence. In some patients, EV resurgence preceded the magnetic resonance imaging detectability of tumor relapse. CONCLUSIONS: Our findings suggest that leakiness of the blood-brain barrier may primarily be responsible for the high circulating EV concentrations in glioblastoma patients. Elevated EVs reflect tumor presence, and their quantification may thus be valuable in assessing disease activity.

Discrimination of benign, atypical, and malignant peripheral nerve sheath tumors in neurofibromatosis type 1 using diffusion-weighted MRI.

Background: Neurofibromatosis type 1 (NF1) is associated with the development of benign (BPNST) and malignant (MPNST) peripheral nerve sheath tumors. Recently described atypical neurofibromas (ANF) are considered pre-malignant precursor lesions to MPNSTs. Previous studies indicate that diffusion-weighted magnetic resonance imaging (DW-MRI) can reliably discriminate MPNSTs from BPNSTs. We therefore investigated the diagnostic accuracy of DW-MRI for the discrimination of benign, atypical, and malignant peripheral nerve sheath tumors. Methods: In this prospective explorative single-center phase II diagnostic study, 44 NF1 patients (23 male; 30.1 ±â€…11.8 years) underwent DW-MRI (b-values 0-800 s/mm²) at 3T. Two radiologists independently assessed mean and minimum apparent diffusion coefficients (ADCmean/min) in areas of largest tumor diameters and ADCdark in areas of lowest signal intensity by manual contouring of the tumor margins of 60 BPNSTs, 13 ANFs, and 21 MPNSTs. Follow-up of ≥ 24 months (BPNSTs) or histopathological evaluation (ANFs + MPNSTs) served as diagnostic reference standard. Diagnostic ADC-based cut-off values for discrimination of the three tumor groups were chosen to yield the highest possible specificity while maintaining a clinically acceptable sensitivity. Results: ADC values of pre-malignant ANFs clustered between BPNSTs and MPNSTs. Best BPNST vs. ANF + MPNST discrimination was obtained using ADCdark at a cut-off value of 1.6 × 10-3 mm2/s (85.3% sensitivity, 93.3% specificity), corresponding to an AUC of 94.3% (95% confidence interval: 85.2-98.0). Regarding BPNST + ANF vs. MPNST, best discrimination was obtained using an ADCdark cut-off value of 1.4 × 10-3 mm2/s (83.3% sensitivity, 94.5% specificity). Conclusions: DW-MRI using ADCdark allows specific and noninvasive discrimination of benign, atypical, and malignant nerve sheath tumors in NF1.

Non-contrast free-breathing 2D CINE compressed SENSE T1-TFE cardiovascular MRI at 3T in sedated young children for assessment of congenital heart disease.

Cardiac MRI is a crucial tool for assessing congenital heart disease (CHD). However, its application remains challenging in young children when performed at 3T. The aim of this retrospective single center study was to compare a non-contrast free-breathing 2D CINE T1-weighted TFE-sequence with compressed sensing (FB 2D CINE CS T1-TFE) with 3D imaging for diagnostic accuracy of CHD, image quality, and vessel diameter measurements in sedated young children. FB 2D CINE CS T1-TFE was compared with a 3D non-contrast whole-heart sequence (3D WH) and 3D contrast-enhanced MR angiography (3D CE-MRA) at 3T in 37 CHD patients (20♂, 1.5±1.4 years). Two radiologists independently assessed image quality, type of CHD, and diagnostic confidence. Diameters and measures of contrast and sharpness of the aorta and pulmonary vessels were determined. A non-parametric multi-factorial approach was used to estimate diagnostic accuracy for the diagnosis of CHD. Linear mixed models were calculated to compare contrast and vessel sharpness. Krippendorff's alpha was determined to quantify vessel diameter agreement. FB 2D CINE CS T1-TFE was rated superior regarding image quality, diagnostic confidence, and diagnostic sensitivity for both intra- and extracardiac pathologies compared to 3D WH and 3D CE-MRA (all p<0.05). FB 2D CINE CS T1-TFE showed superior contrast and vessel sharpness (p<0.001) resulting in the highest proportion of measurable vessels (740/740; 100%), compared to 3D WH (530/620; 85.5%) and 3D CE-MRA (540/560; 96.4%). Regarding vessel diameter measurements, FB 2D CINE CS T1-TFE revealed the closest inter-reader agreement (Krippendorff's alpha: 0.94-0.96; 3D WH: 0.78-0.94; 3D CE-MRA: 0.76-0.93). FB 2D CINE CS T1-TFE demonstrates robustness at 3T and delivers high-quality diagnostic results to assess CHD in sedated young children. Its ability to function without contrast injection and respiratory compensation enhances ease of use and could encourage widespread adoption in clinical practice.

Myocardial strain assessment in the human fetus by cardiac MRI using Doppler ultrasound gating and feature tracking.

OBJECTIVES: Assessment of myocardial strain by feature tracking magnetic resonance imaging (FT-MRI) in human fetuses with and without congenital heart disease (CHD) using cardiac Doppler ultrasound (DUS) gating. METHODS: A total of 43 human fetuses (gestational age 28-41 weeks) underwent dynamic cardiac MRI at 3 T. Cine balanced steady-state free-precession imaging was performed using fetal cardiac DUS gating. FT-MRI was analyzed using dedicated post-processing software. Endo- and epicardial contours were manually delineated from fetal cardiac 4-chamber views, followed by automated propagation to calculate global longitudinal strain (GLS) of the left (LV) and right ventricle (RV), LV radial strain, and LV strain rate. RESULTS: Strain assessment was successful in 38/43 fetuses (88%); 23 of them had postnatally confirmed diagnosis of CHD (e.g., coarctation, transposition of great arteries) and 15 were heart healthy. Five fetuses were excluded due to reduced image quality. In fetuses with CHD compared to healthy controls, median LV GLS (- 13.2% vs. - 18.9%; p < 0.007), RV GLS (- 7.9% vs. - 16.2%; p < 0.006), and LV strain rate (1.4 s-1 vs. 1.6 s-1; p < 0.003) were significantly higher (i.e., less negative). LV radial strain was without a statistically significant difference (20.7% vs. 22.6%; p = 0.1). Bivariate discriminant analysis for LV GLS and RV GLS revealed a sensitivity of 67% and specificity of 93% to differentiate between fetuses with CHD and healthy fetuses. CONCLUSION: Myocardial strain was successfully assessed in the human fetus, performing dynamic fetal cardiac MRI with DUS gating. Our study indicates that strain parameters may allow for differentiation between fetuses with and without CHD. CLINICAL RELEVANCE STATEMENT: Myocardial strain analysis by cardiac MRI with Doppler ultrasound gating and feature tracking may provide a new diagnostic approach for evaluation of fetal cardiac function in congenital heart disease. KEY POINTS: • MRI myocardial strain analysis has not been performed in human fetuses so far. • Myocardial strain was assessed in human fetuses using cardiac MRI with Doppler ultrasound gating. • MRI myocardial strain may provide a new diagnostic approach to evaluate fetal cardiac function.

Real-time multi-contrast magnetic particle imaging for the detection of gastrointestinal bleeding.

Gastrointestinal bleeding, as a potentially life-threatening condition, is typically diagnosed by radiation-based imaging modalities like computed tomography or more invasively catheter-based angiography. Endoscopy enables examination of the upper gastrointestinal tract and the colon but not of the entire small bowel. Magnetic Particle Imaging (MPI) enables non-invasive, volumetric imaging without ionizing radiation. The aim of this study was to evaluate the feasibility of detecting gastrointestinal bleeding by single- and multi-contrast MPI using human-sized organs. A 3D-printed small bowel phantom and porcine small bowel specimens were prepared with a defect within the bowel wall as the source of a bleeding. For multi-contrast MPI, the bowel lumen was filled with an intestinal tracer representing an orally administered tracer. MPI was performed to evaluate the fluid exchange between the vascular compartment of the bowel wall and the lumen while a blood pool tracer was applied. Leakage of the blood pool tracer was observed to the bowel lumen. Multi-contrast MPI enabled co-registration of both tracers at the same location within the bowel lumen indicating gastrointestinal bleeding. Single- and multi-contrast MPI are feasible to visualize gastrointestinal bleeding. Therefore, MPI might emerge as a useful tool for radiation-free detection of bleeding within the entire gastrointestinal tract.

Assessment of aortic diameter in Marfan patients: intraindividual comparison of 3D-Dixon and 2D-SSFP magnetic resonance imaging.

OBJECTIVES: To compare the accuracy and precision of 3D-Dixon and 2D-SSFP MR-imaging for assessment of aortic diameter in Marfan patients. METHODS: This prospective single-center study investigated respiratory-gated 3D-Dixon and breath-hold 2D-SSFP non-contrast MR-imaging at 3 T in 47 Marfan patients (36.0 ± 13.2 years, 28♀,19♂). Two radiologists performed individual diameter measurements at five levels of the thoracic aorta and evaluated image quality on a four-grade scale (1 = poor, 4 = excellent) and artifacts (1 = severe, 4 = none). Aortic root diameters acquired by echocardiography served as a reference standard. Intraclass correlation coefficient, Bland-Altman analyses, F-test, t-test, and regression analyses were used to assess agreement between observers and methods. RESULTS: Greatest aortic diameters were observed at the level of the sinuses of Valsalva (SOV) for 3D-Dixon (38.2 ± 6.8 mm) and 2D-SSFP (38.3 ± 7.1 mm) (p = 0.53). Intra- and interobserver correlation of diameter measurements was excellent at all aortic levels for both 3D-Dixon (r = 0.94-0.99 and r = 0.94-0.98) and 2D-SSFP (r = 0.96-1.00 and r = 0.95-0.99). 3D-Dixon-derived and 2D-SSFP-derived diameter measurements at the level of the SOV revealed a strong correlation with echocardiographic measurements (r = 0.92, p < 0.001 and r = 0.93, p < 0.001, respectively). The estimated mean image quality at the level of SOV was higher for 2D-SSFP compared to that for 3D-Dixon (3.3 (95%-CI: 3.1-3.5) vs. 2.9 (95%-CI: 2.7-3.1)) (p < 0.001). Imaging artifacts were less at all aortic levels for 3D-Dixon compared to 2D-SSFP (3.4-3.8 vs. 2.8-3.1) (all p < 0.002). CONCLUSION: Respiratory-gated 3D-Dixon and breath-hold 2D-SSFP MR-imaging provide accurate and precise aortic diameter measurements. We recommend 3D-Dixon imaging for monitoring of aortic diameter in Marfan patients due to fewer imaging artifacts and the possibility of orthogonal multiplanar reformations of the aortic root. KEY POINTS: • Respiratory-gated 3D-Dixon and breath-hold 2D-SSFP imaging provide accurate and precise aortic diameter measurements in patients suffering from Marfan syndrome. • Imaging artifacts are stronger in 2D-SFFP imaging than in 3D-Dixon imaging. • We recommend 3D-Dixon imaging for monitoring of aortic diameter in Marfan patients due to fewer imaging artifacts and the possibility of orthogonal multiplanar reformations.

Comparison of cine cardiac magnetic resonance and echocardiography derived diameters of the aortic root in a large population-based cohort.

Transthoracic echocardiography (TTE) and cine cardiac magnetic resonance imaging (CMR) are established imaging methods of the aortic root. We aimed to evaluate the comparability of measurements in TTE and standard cine CMR sequences of the aortic root. Our study included 741 subjects (mean age 63.5 ± 8 years, 43.7% female) from the Hamburg City Health Study (HCHS). Subjects underwent CMR and TTE. Aortic root measurements were performed at the level of the aortic annulus (AoAn), sinus of Valsalva (SoV), and sinotubular junction (STJ) by standard cine CMR in left ventricular long axis and left ventricular outflow tract view. Measurements were performed applying the leading-edge to leading-edge (LL) convention and inner-edge to inner-edge (II) convention in TTE and the II convention in CMR. Inter correlation coefficients (ICCs) demonstrated high inter- and intraobserver reproducibility for CMR and TTE measurements of SoV and STJ (ICCs 0.9-0.98) and moderate reproducibility for AoAn (ICCs 0.68-0.91). CMR measurements of SoV and STJ showed strong agreement with TTE: while correlations were comparable (r = 0.75-0.85) bias was lower with TTE II (bias - 0.1 to - 0.74) versus TTE LL measurements (mean bias - 1.49 to - 2.58 mm). The agreement for AoAn was fair (r = 0.51-0.57) with variable bias (mean bias 0.39-3.9). Standard cine CMR and TTE derived aortic root measurements are reproducible and comparable with higher agreement for TTE II instead of LL measurements. These results support an interchangeable application of TTE and standard CMR for screening of aortic root diseases thereby possibly reducing redundant multimodality imaging.

First Dedicated Balloon Catheter for Magnetic Particle Imaging.

Vascular interventions are a promising application of Magnetic Particle Imaging enabling a high spatial and temporal resolution without using ionizing radiation. The possibility to visualize the vessels as well as the devices, especially at the same time using multi-contrast approaches, enables a higher accuracy for diagnosis and treatment of vascular diseases. Different techniques to make devices MPI visible have been introduced so far, such as varnish markings or filling of balloons. However, all approaches include challenges for in vivo applications, such as the stability of the varnishing or the visibility of tracer filled balloons in deflated state. In this contribution, we present for the first time a balloon catheter that is molded from a granulate incorporating nanoparticles and can be visualized sufficiently in MPI. Computed tomography is used to show the homogeneous distribution of particles within the material. Safety measurements confirm that the incorporation of nanoparticles has no negative effect on the balloon. A dynamic experiment is performed to show that the inflation as well as deflation of the balloon can be imaged with MPI.

Systematic evaluation of hydrophobic deep eutectic solvents as alternative media for the extraction of metal ions from aqueous solution.

The recent development of hydrophobic deep eutectic solvents (HDESs) has led to growing interest in these reagents as possible environmentally benign replacements for conventional organic media in a host of applications, among them metal ion separations by liquid-liquid extraction. To evaluate the potential utility of these novel solvents in this application, a systematic examination of the facilitated transfer of selected alkali and alkaline earth cations into representative HDESs from aqueous solution in the presence of a macrocyclic polyether (i.e., a crown ether) has been undertaken. Comparison of the results to those obtained for a series of oxygenated, aliphatic solvents (n-alcohols) and for several 1-alkyl-3-methylimidazolium-based ionic liquids (ILs) under the same conditions indicate that despite frequent suggestions that some HDESs resemble ILs, metal ion distribution in HDES-aqueous systems more closely mimics that seen for the alcohols. Metal ion partitioning in these systems appears less dependent on the water content of the organic phase and on structural variations in the solvent than is the case for either alcohols or ionic liquids, however. The implications of these results for the design and application of HDES-based extraction systems for metal ions are described.

Single-nanometer iron oxide nanoparticles as tissue-permeable MRI contrast agents.

Magnetic nanoparticles are robust contrast agents for MRI and often produce particularly strong signal changes per particle. Leveraging these effects to probe cellular- and molecular-level phenomena in tissue can, however, be hindered by the large sizes of typical nanoparticle contrast agents. To address this limitation, we introduce single-nanometer iron oxide (SNIO) particles that exhibit superparamagnetic properties in conjunction with hydrodynamic diameters comparable to small, highly diffusible imaging agents. These particles efficiently brighten the signal in T1-weighted MRI, producing per-molecule longitudinal relaxation enhancements over 10 times greater than conventional gadolinium-based contrast agents. We show that SNIOs permeate biological tissue effectively following injection into brain parenchyma or cerebrospinal fluid. We also demonstrate that SNIOs readily enter the brain following ultrasound-induced blood-brain barrier disruption, emulating the performance of a gadolinium agent and providing a basis for future biomedical applications. These results thus demonstrate a platform for MRI probe development that combines advantages of small-molecule imaging agents with the potency of nanoscale materials.

Accuracy of preoperative CT staging of acute colonic diverticulitis using the classification of diverticular disease (CDD) - Is there a beneficial impact of water enema and visceral obesity?

PURPOSE: We evaluated the accuracy of preoperative CT in staging colonic diverticulitis (ACD) by using the classification of diverticular disease (CDD) and investigated the diagnostic impact of water enema (WE) and visceral obesity. METHODS: In this retrospective study, the radiological and hospital information system was searched for patients who underwent CT for clinically suspected ACD prior to surgery between 2009 and 2019. From the initial population (n = 164), we included 155 patients (94.5 %) (85 women; mean age: 58 ±â€¯13 years) matching the following inclusion criteria: i.) clinically suspected ACD, ii.) i.v. contrast-enhanced CT, iii.) surgery for ACD within 1 week after CT, iv.) histopathological report that proved ACD. The remaining 9 patients (5.5 %) were excluded because histopathological reports were lacking (n = 3) or CT was performed without intravenous contrast agent (n = 6). WE (+ butylscopolamine i.v.) was performed in 93 patients (group A, 60 %). 62 patients (group B, 40 %) had no WE. Visceral-to-subcutaneous fat ratio (V/S) was determined for each patient. Two radiologists blinded for final diagnosis independently staged ACD according to CDD and assessed prevalence and confidence ratings of ACD-related CT-findings: pericolonic fat stranding, covered- and free-perforation, local and generalized peritonitis, abscess. Interobserver-agreement of CT-findings were assessed and effects of WE and V/S ratio on the diagnostic accuracy of CT with surgical and histopathological findings as reference were determined by calculating a logistic regression model. RESULTS: CT-staging showed high accuracy (94 %) and excellent interrater-correlation (ICC 0.96) for staging ACD. WE had no positive impact neither on diagnostic accuracy of staging, nor on confidence ratings of ACD-related CT-findings (all p > 0.5). Confidence ratings were significantly higher in examinations without WE for perforation, peritonitis as well as abscesses (all p < 0.5). Confidence ratings for the assessment of local peritonitis improved significantly with higher V/S (p = 0.049). The increase of V/S significantly correlated with the probability for correct CDD staging of ACD in CT (p = 0.023). CONCLUSION: Increase of visceral obesity significantly improves accuracy of CT in preoperative staging acute colonic diverticulitis. However, independently of the degree of visceral obesity, water enema has no diagnostic benefit and may therefore be omitted. Overall, CT proves high accuracy in preoperative staging ACD using the classification of diverticular disease. LEVEL OF EVIDENCE: Retrospective study, observational study.

Pulmonary blood volume estimation in mice by magnetic particle imaging and magnetic resonance imaging.

This methodical work describes the measurement and calculation of pulmonary blood volume in mice based on two imaging techniques namely by using magnetic particle imaging (MPI) and cardiac magnetic resonance imaging (MRI). Besides its feasibility aspects that may influence quantitative analysis are studied. Eight FVB mice underwent cardiac MRI to determine stroke volumes and anatomic MRI as morphological reference for functional MPI data. Arrival time analyses of boli of 1 µl of 1 M superparamagnetic tracer were performed by MPI. Pulmonary transit time of the bolus was determined by measurements in the right and left ventricles. Pulmonary blood volume was calculated out of stroke volume, pulmonary transit time and RR-interval length including a maximal error analysis. Cardiac stroke volume was 31.7 µl ± 2.3 µl with an ejection fraction of 71% ± 6%. A sharp contrast bolus profile was observed by MPI allowing subdividing the first pass into three distinct phases: tracer arrival in the right ventricle, pulmonary vasculature, and left ventricle. The bolus full width at half maximum was 578 ms ± 144 ms in the right ventricle and 1042 ms ± 150 ms in the left ventricle. Analysis of pulmonary transit time revealed 745 ms ± 81 ms. Mean RR-interval length was 133 ms ± 12 ms. Pulmonary blood volume resulted in 177 µl ± 27 µl with a mean maximal error limit of 27 µl. Non-invasive assessment of the pulmonary blood volume in mice was feasible. This technique can be of specific value for evaluation of pulmonary hemodynamics in mouse models of cardiac dysfunction or pulmonary disease. Pulmonary blood volume can complement cardiac functional parameters as a further hemodynamic parameter.

Increased urinary bladder volume improves the detectability of urinary stones at the ureterovesical junction in non-enhanced computed tomography (NECT).

OBJECTIVES: To evaluate the influence of the urinary bladder volume on the detectability of urolithiasis at the ureterovesical junction (UVJ) using a low-dose CT (LD-CT) with iterative reconstruction (IR) and a standard-dose CT (SD-CT) without IR in a large cohort. METHODS: Four hundred patients (278 males (69.5%), mean 44.6 ± 14.7 years) with urolithiasis at the UVJ were investigated either by an LD-CT with IR (n = 289, 72%) or an SD-CT without IR (n = 111, 28%) protocol. The detectability of distal urolithiasis was assessed by a dichotomous assessment (definite or questionable) by two radiologists in consensus and by a quantitative analysis of the signal density distribution across a line drawn parallel to the distal ureter. Based on the resulting graph, minimum/maximum density values and mean/maximum upslopes and downslopes were derived and calculated automatically. In all patients, the total bladder volume was calculated by a slice-by-slice approach on axial CT images. RESULTS: Patients with definite stones showed significantly higher urinary bladder volumes compared to patients with questionable stones in both LD-CT and SD-CT (p < 0.01). These results were independent of stones' length and patients' BMI values. Using cutoffs of 92 ml for LD-CT and 69 ml for SD-CT, high positive predictive values/accuracy rates of 96%/85% (LD-CT) and 98%/86% (SD-CT) were observed to identify definite urinary stones. CONCLUSIONS: Urinary bladder volume has a significant impact on the detectability of distal urolithiasis. Moderate bladder filling by pre-CT hydration with subsequent CT scan at the time of high urge to void increases the detectability of urinary stones at the UVJ in clinical routine. KEY POINTS: • Urinary bladder volume significantly affects the detectability of distal urolithiasis • Higher bladder volumes are associated with improved detectability of distal urinary stones • Oral pre-CT hydration for urolithiasis is easily applicable and cost-effective.

Differentiation of peripheral nerve sheath tumors in patients with neurofibromatosis type 1 using diffusion-weighted magnetic resonance imaging.

BACKGROUND: We sought to determine the value of diffusion-weighted (DW) magnetic resonance imaging (MRI) for characterization of benign and malignant peripheral nerve sheath tumors (PNSTs) in patients with neurofibromatosis type 1 (NF1). METHODS: Twenty-six patients with NF1 and suspicion of malignant transformation of PNSTs were prospectively enrolled and underwent DW MRI at 3T. For a set of benign (n = 55) and malignant (n = 12) PNSTs, functional MRI parameters were derived from both biexponential intravoxel incoherent motion (diffusion coefficient D and perfusion fraction f) and monoexponential data analysis (apparent diffusion coefficients [ADCs]). A panel of morphological MRI features was evaluated using T1- and T2-weighted imaging. Mann-Whitney U-test, Fisher's exact test, and receiver operating characteristic (ROC) analyses were applied to assess the diagnostic accuracy of quantitative and qualitative MRI. Cohen's kappa was used to determine interrater reliability. RESULTS: Malignant PNSTs demonstrated significantly lower diffusivity (P < 0.0001) compared with benign PNSTs. The perfusion fraction f was significantly higher in malignant PNSTs (P < 0.001). In ROC analysis, functional MRI parameters showed high diagnostic accuracy for differentiation of PNSTs (eg, ADCmean, 92% sensitivity with 98% specificity, AUC 0.98; Dmean, 92% sensitivity with 98% specificity, AUC 0.98). By contrast, morphological imaging features had only limited sensitivity (18-94%) and specificity (18-82%) for identification of malignancy. Interrater reliability was higher for monoexponential data analysis. CONCLUSION: DW imaging shows better diagnostic performance than morphological features and allows accurate differentiation of benign and malignant peripheral nerve sheath tumors in NF1.

Systematic evaluation of hydrophobic deep-melting eutectics as alternative solvents for the extraction of organic solutes from aqueous solution.

The partitioning of a number of organic compounds, including a series of n-alkanols and various simple, substituted benzene derivatives, between several hydrophobic (i.e., water-immiscible) deep eutectic solvents (HDESs) and water has been examined. The extent of extraction is shown to vary with the charge state of the molecule and the composition of the eutectic. In addition, the HDES-water distribution of a given solute is found to be directly proportional to (but typically less than) its partitioning in the octanol-water system, consistent with a significant role for solute hydrophobicity in the observed extraction behavior. Comparison of solute extraction into an HDES to that observed for other "unconventional" solvents (e.g., room-temperature ionic liquids and a soybean-derived oil) shows that hydrophobic deep eutectic solvents provide comparable or superior extraction efficiency.

Preoperative evaluation of pelvine lymph node metastasis in high risk prostate cancer with intravoxel incoherent motion (IVIM) MRI.

OBJECTIVES: To evaluate benign and malignant pelvine lymph nodes in prostate cancer patients with biexponential intravoxel incoherent motion (IVIM) MRI of the prostate prior to radical prostatectomy. METHODS: The ethics committee approved this retrospective study with waiver of informed consent. From February 2012 to November 2013 43 patients with histopathologically proven prostatic cancer were included. All patients were examined applying a standardized MRI protocol including IVIM diffusion weighted imaging with multiple b-values ranging from 0 to 950 s/mm². MR imaging was performed one day prior to radical prostatectomy. Thereafter, extended lymph node resection was performed. For each MRI all visible lymph nodes were registered and calculated as individual regions of interest. These findings were correlated with postoperative pathology. The apparent diffusion coefficient ADC, the diffusion coefficient D and the perfusion fraction f were calculated from IVIM DWI using a biexponential fit. RESULTS: A total of 120 lymph nodes were detected on MRI. 95 of these were determined as benign and 25 as malignant. The average ADC was significantly lower in malignant compared to benign lymph nodes (0.88 × 10-³ vs 1.67 × 10-³ mm²/s, p < 0.001). Likewise, the average diffusion coefficient D was significantly lower in lymph node metastasis (0.54 × 10-³ vs 1.10 × 10-³ mm²/s, p < .001). The signal rate due to perfusion was significantly higher in malignant compared to benign nodes (33.4% vs. 27.1%, p = 0.02). CONCLUSIONS: Applying biexponential IVIM MRI demonstrates significant differences in diffusion parameters ADC and D, as well as in the perfusion fraction f for benign and malignant lymph nodes. Therefore, IVIM might help to further improve the preoperative assessment of lymph nodes in MRI.

T2 relaxation times of the anterolateral femoral cartilage in patients after ACL-reconstruction with and without a deep lateral femoral notch sign.

PURPOSE: To quantitatively assess T2 relaxation times of the anterolateral femoral cartilage following anterior cruciate ligament (ACL)-reconstruction with and without a positive deep lateral femoral notch sign (DLNS) at post-traumatic MRI. MATERIALS AND METHODS: In 52 patients post-traumatic MRI as well as 12 months after ACL-rupture (ACLR) and surgical treatment were analysed. In 28 patients a positive DLNS was present at post-traumatic MRI. For quantitative analysis, T2 relaxation time measurements (7 TE: 10-70 ms) were performed at time of re-evaluation. Three polygonal ROIs encompassing the full cartilage layer were placed in the anterolateral femoral cartilage. Clinical assessment included Lysholm-Tegner-Activity-Score, Rasmussen's clinical score and modified Cincinnati-Rating-System-Questionnaire. Description and differences were calculated as means and confidence intervals of means, controlled for the cluster effect of person, if appropriate. RESULTS: In patients with a positive DLNS after ACLR, relaxation times in the notch region were significantly prolonged compared to patients without a positive DLNS (Δ 7.4 ms, CI: 5.6-9.2; p-value <0.001) as well as to the adjacent anterior (Δ 5.7 ms, CI: 4.7-6.7; p-value <0.001) and central femoral cartilage (Δ 6.6 ms, CI: 5.7-7.6; p-value <0.001). Solely insignificant differences were noticed in the performed clinical scores comparing the two groups (p > 0.05). CONCLUSION: Significantly prolonged T2 relaxation times of the anterolateral femoral cartilage were found in patients with a positive DLNS following ACL-reconstruction compared to patients without a DLNS. Based on these results, it has to be assumed that a positive DLNS is associated with higher cartilage degradation.

Inter- and Intraobserver reproducibility of T2 relaxation times of the discus interpubicus: A feasibility study at 3 Tesla.

OBJECTIVE: To quantify standard values of the discus interpubicus in healthy subjects and to determine reliability and repeatability using T2 relaxation time measurements at 3T. METHODS: 20 asymptomatic participants (10 male, 10 female; mean age: 27.3 years ±4.1, BMI: 22.2 ±1.8) underwent a 3T Magnetic Resonance Imaging (MRI) of the pelvic region in a supine position. We included sagittal and para-axial T2w sequences centred over the pubic symphysis in order to identify the complete discus interpubicus. For quantitative analysis, a multi-echo Turbo Spin Echo (TSE) sequence (including 12 echo times between 6.4 and 76.8 ms) was acquired and analysed by using an in-house developed quantification plugin tool (qMapIt) extending ImageJ. Two readers in consensus defined three central slices of the pubic symphysis with the greatest length. For each slice, both readers separately placed three regions-of-interest (ROI) covering the whole discus interpubicus. Both readers repeated the ROI placements in identical fashion after a four-week interval on the original MRI images. Statistical analysis included intraclass correlation coefficient (ICC), nonparametric Wilcoxon test, Fisher exact test and mean relaxation time in ms and 95% confidence intervals. RESULTS: T2 relaxation time analysis was performed for all 20 participants. In total, a mean relaxation time of all analysed segments for both observers was 48.6 (±6.3 ms), with a mean relaxation time for observer 1 of 48.7 (±6.0 ms) and for observer 2 of 48.5 ms (±6.6ms). The calculated ICC comparing inter- and intrarater reproducibility was excellent in all segments (≥0.75). CONCLUSION: T2 mapping of the discus interpubicus demonstrates good inter- and intrarater repeatability as well as reliability. Mean relaxation times were calculated with 48.6ms in healthy volunteers.

Evaluating size-dependent relaxivity of PEGylated-USPIOs to develop gadolinium-free T1 contrast agents for vascular imaging.

Ultra-small superparamagnetic iron oxide (USPIO) nanoparticles provide a safer alternative to gadolinium-based contrast agents (GBCAs) in T1-weighted MR imaging. MRI contrast behavior of USPIOs depends on their magnetic properties, which in turn depend on their physicochemical composition. Identifying and tailoring USPIO structural characteristics that influence proton relaxation in MRI is crucial to developing effective gadolinium-free T1 contrast agents. Here, we present a systematic empirical evaluation of the relationship between USPIO size and MRI relaxivity (r1 and r2 values). Monodisperse USPIO cores, with precisely controlled core diameter (dC ) were synthesized via the thermal decomposition of iron(III)-oleate precursor. USPIOs with dC = 6.34, 7.58, 8.58, and 9.50nm, were dispersed in aqueous phase via ligand exchange with silane or dopamine-modified polyethylene glycol (PEG) polymers. Relaxivity characterization in a 1.5 T clinical MRI scanner showed the r2 /r1 ratio increased linearly with USPIO core diameter (R2 = 0.95), but varied little with both hydrodynamic diameter (dH ) and PEG molecular weight. One sample, DOPA-6-20 (6.34nm USPIO cores coated with 20 kDa dopamine-modified PEG), provided the lowest r2 /r1 value (3.44) and thus promise as a potential T1 contrast agent. In a preliminary study, we evaluated DOPA-6-20 for in vivo angiography imaging in a mouse with a 7 T scanner and observed strong T1-weighted enhancement of the mouse blood pool. Key anatomical features in the vascular network were visible even 5 min after intravenous administration. Using empirical data, we have presented the basis of a structure-property relationship that can help develop optimized USPIO-based T1 contrast agents. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A:2440-2447, 2018.

Magnetic particle imaging for in vivo blood flow velocity measurements in mice.

Magnetic particle imaging (MPI) is a new imaging technology. It is a potential candidate to be used for angiographic purposes, to study perfusion and cell migration. The aim of this work was to measure velocities of the flowing blood in the inferior vena cava of mice, using MPI, and to evaluate it in comparison with magnetic resonance imaging (MRI). A phantom mimicking the flow within the inferior vena cava with velocities of up to 21 cm s-1 was used for the evaluation of the applied analysis techniques. Time-density and distance-density analyses for bolus tracking were performed to calculate flow velocities. These findings were compared with the calibrated velocities set by a flow pump, and it can be concluded that velocities of up to 21 cm s-1 can be measured by MPI. A time-density analysis using an arrival time estimation algorithm showed the best agreement with the preset velocities. In vivo measurements were performed in healthy FVB mice (n = 10). MRI experiments were performed using phase contrast (PC) for velocity mapping. For MPI measurements, a standardized injection of a superparamagnetic iron oxide tracer was applied. In vivo MPI data were evaluated by a time-density analysis and compared to PC MRI. A Bland-Altman analysis revealed good agreement between the in vivo velocities acquired by MRI of 4.0 ± 1.5 cm s-1 and those measured by MPI of 4.8 ± 1.1 cm s-1. Magnetic particle imaging is a new tool with which to measure and quantify flow velocities. It is fast, radiation-free, and produces 3D images. It therefore offers the potential for vascular imaging.