Diffusion Coefficient Measurements Research Articles

Europium diffusion in IG-110 nuclear graphite

Europium diffusion in graphite has been recognized to be of interest in high-temperature gas reactor safety analysis, particularly as an indicator of strontium diffusion. However, no measurements of europium diffusion coefficients have been reported in the literature. In this work, the effective diffusion coefficient of europium was measured using a time-release method. Natural europium was loaded into pre-milled unirradiated IG-110 graphite spheres using a pressurized acid digestion vessel. The time-release experiments were performed in the temperature range 1823 K – 1973 K using a SiC diffusion cell connected to an inductively-coupled plasma mass spectrometer (ICP-MS) via a He gas line. The results of this work are:DEu,IG−110=(1.5×10−3m2/s)exp(−2.87×105J/molRT)This effective diffusion coefficient can be used to aid in predictive modelling of europium transport in HTGRs.

Detection of impaired renal allograft function in paediatric and young adult patients using arterial spin labelling MRI (ASL-MRI)

The study aimed to discriminate renal allografts with impaired function by measuring cortical renal blood flow (cRBF) using magnetic resonance imaging arterial spin labelling (ASL-MRI) in paediatric and young adult patients. We included 18 subjects and performed ASL-MRI on 1.5 T MRI to calculate cRBF on parameter maps. cRBF was correlated to calculated glomerular filtration rate (GFR) and compared between patient groups with good (GFR ≥ 60 mL/min/1.73 m2) and impaired allograft function (GFR < 60 mL/min/1.73 m2). Mean cRBF in patients with good allograft function was significantly higher than in patients with impaired allograft function (219.89 ± 57.24 mL/min/100 g vs. 146.22 ± 41.84 mL/min/100 g, p < 0.008), showing a highly significant correlation with GFR in all subjects (r = 0.75, p < 0.0001). Also, the diffusion-weighted imaging (DWI-MRI) apparent diffusion coefficient (ADC) and Doppler measurements of peak-systolic and end-diastolic velocities and the resistive index (PS, ED, RI) were performed and both methods showed no significant difference between groups. ADC implied no correlation with GFR (r = 0.198, p = 0.464), while PS indicated moderate correlation to GFR (r = 0.48, p < 0.05), and PS and ED moderate correlation to cRBF (r = 0.58, p < 0.05, r = 0.56, p < 0.05, respectively). Cortical perfusion as non-invasively measured by ASL-MRI differs between patients with good and impaired allograft function and correlates significantly with its function.

Measurement of diffusion coefficients of hydrogen sulfide in water and brine using in-situ Raman spectroscopy

Diffusion coefficients of hydrogen sulfide in water and brine are critical in geology and chemical industries for hydrogen sulfide geological storage and hydrogen sulfide separation from natural gas. However, previous studies have mostly measured the diffusion coefficient of hydrogen sulfide in water at room temperature and normal pressure and the diffusion coefficient of hydrogen sulfide in brine had not been reported. In this study, ratio of the Raman signal intensity of the H-S bond of hydrogen sulfide to the HO bond of water, HRH2S/H2O, was used to measure the diffusion coefficients of hydrogen sulfide in water at 0.1–2 MPa and 273.1–373.1 K and in four brine solutions (0.62, 1, 2, and 3 mol•kg−1 NaCl) at 1 MPa and 273.1–373.1 K. Results showed that the diffusion coefficient of hydrogen sulfide in water increased with the increasing temperature and was insignificantly affected by the pressure, which follows the relationship derived from the Speedy–Angell power-law: D(cm2/s)=13.013×10−5[T/216.478−1]1.974, where T is in the temperature (K). In brine, the diffusion coefficient of hydrogen sulfide also increased with the temperature and was clearly inhibited by salinity, which can be described using the Ratcliff–Holdcroft model D(cm2/s)=13.013×10−5(T/216.478)1.974(1−0.0755Cs), where Cs is concentration of NaCl in brine (mol•kg−1).

Interstitial Brachytherapy of the Liver for Renal Cell Carcinoma: ADC Measurements Do Not Predict Overall Survival.

To assess the influence of pre-treatment apparent diffusion coefficient (ADC) measurements on outcomes in patients undergoing interstitial brachytherapy (iBT) for liver metastases from renal cell carcinoma. Patients undergoing iBT for renal cell carcinoma (RCC) liver metastases were retrospectively identified. Patients were eligible for inclusion if they had a pre-treatment magnetic resonance imaging (MRI) with diffusion weighted imaging (DWI) sequences. For each lesion, a region of interest (ROI) was placed along the contours of the entire lesion across all slices. For each ROI, ADC minimum, mean and maximum as well as the lesion area were noted, and the average was calculated for each lesion. ADC measurements were correlated with overall survival. The analysis included 17 patients. Median overall survival was 36 months. Neither ADC measurement was significantly associated with overall survival. ADC min (HR=1.00, 95%CI=1.00-1.00, p=0.600), ADC max (HR=1.001, 95%CI=0.998-1.003, p=0.490), ADC mean (HR=0.999, 95%CI=0.996-1.003, p=0.638). ADC is not able to differentiate between groups with good and bad overall survival in patients undergoing iBT for RCC liver metastases.

Accuracy of fractal analysis and PI-RADS assessment of prostate magnetic resonance imaging for prediction of cancer grade groups: a clinical validation study

ObjectivesMultiparametric MRI with Prostate Imaging Reporting and Data System (PI-RADS) assessment is sensitive but not specific for detecting clinically significant prostate cancer. This study validates the diagnostic accuracy of the recently suggested fractal dimension (FD) of perfusion for detecting clinically significant cancer.Materials and methodsRoutine clinical MR imaging data, acquired at 3 T without an endorectal coil including dynamic contrast-enhanced sequences, of 72 prostate cancer foci in 64 patients were analyzed. In-bore MRI-guided biopsy with International Society of Urological Pathology (ISUP) grading served as reference standard. Previously established FD cutoffs for predicting tumor grade were compared to measurements of the apparent diffusion coefficient (25th percentile, ADC25) and PI-RADS assessment with and without inclusion of the FD as separate criterion.ResultsFractal analysis allowed prediction of ISUP grade groups 1 to 4 but not 5, with high agreement to the reference standard (κFD = 0.88 [CI: 0.79–0.98]). Integrating fractal analysis into PI-RADS allowed a strong improvement in specificity and overall accuracy while maintaining high sensitivity for significant cancer detection (ISUP > 1; PI-RADS alone: sensitivity = 96%, specificity = 20%, area under the receiver operating curve [AUC] = 0.65; versus PI-RADS with fractal analysis: sensitivity = 95%, specificity = 88%, AUC = 0.92, p < 0.001). ADC25 only differentiated low-grade group 1 from pooled higher-grade groups 2–5 (κADC = 0.36 [CI: 0.12–0.59]). Importantly, fractal analysis was significantly more reliable than ADC25 in predicting non-significant and clinically significant cancer (AUCFD = 0.96 versus AUCADC = 0.75, p < 0.001). Diagnostic accuracy was not significantly affected by zone location.ConclusionsFractal analysis is accurate in noninvasively predicting tumor grades in prostate cancer and adds independent information when implemented into PI-RADS assessment. This opens the opportunity to individually adjust biopsy priority and method in individual patients.Key Points• Fractal analysis of perfusion is accurate in noninvasively predicting tumor grades in prostate cancer using dynamic contrast-enhanced sequences (κFD = 0.88).• Including the fractal dimension into PI-RADS as a separate criterion improved specificity (from 20 to 88%) and overall accuracy (AUC from 0.86 to 0.96) while maintaining high sensitivity (96% versus 95%) for predicting clinically significant cancer.• Fractal analysis was significantly more reliable than ADC25 in predicting clinically significant cancer (AUCFD = 0.96 versus AUCADC = 0.75).

Probing Allosteric Modulation of Membrane Receptor in the Native State by Data Mining-Integrated Tracking Microscopy

Probing Allosteric Modulation of Membrane Receptor in the Native State by Data Mining-Integrated Tracking Microscopy

Three-dimensional diffusion coefficient measurement by a large depth-of-field rotating point spread function.

A prominent challenge in single-molecule localization microscopy is the real-time, fast, and accurate localization of nano-objects moving in three-dimensional (3D) samples. A well-established method for 3D single-molecule localization is the double-helix pointspread-function (DH-PSF) engineering, which uses additional optical elements to make the PSF exhibit different rotation angles with different nanoparticle depths. However, the compact main lobe size, effective detection depth, and precise conversion between rotation angle and depth are necessary, posing challenges to the DH-PSF generation method. Here we generate a more compact DH-PSF using Fresnel-zone-based spiral phases, and the pure phase mask achieves high transmission efficiency. The final generated DH-PSFs have a linear rotation rate at each axial position, showing a more accurate rotation angle and depth conversion. The Cramer-Rao lower limit calculation results show that the axial depth of DH-PSF extends to ∼11µm with an axial localization precision of ∼45nm at 3000 photons and average background noise of 15. We measured the diffusion coefficient of nanospheres in different concentrations of glycerol using the generated DH-PSF. The measured results are within 6% error from the theoretical values, indicating the superior performance of the DH-PSF for nanoparticle diffusion coefficient measurements.

Following Molecular Mobility during Chemical Reactions: No Evidence for Active Propulsion.

The reported changes in self-diffusion of small molecules during reactions have been attributed to "boosted mobility". We demonstrate the critical role of changing concentrations of paramagnetic ions on nuclear magnetic resonance (NMR) signal intensities, which led to erroneous measurements of diffusion coefficients. We present simple methods to overcome this problem. The use of shuffled gradient amplitudes allows accurate diffusion NMR measurements, even with time-dependent relaxation rates caused by changing concentrations of paramagnetic ions. The addition of a paramagnetic relaxation agent allows accurate determination of both diffusion coefficients and reaction kinetics during a single experiment. We analyze a copper-catalyzed azide-alkyne cycloaddition "click" reaction, for which boosted mobility has been claimed. With our methods, we accurately measure the diffusive behavior of the solvent, starting materials, and product and find no global increase in diffusion coefficients during the reaction. We overcome NMR signal overlap using an alternative reducing agent to improve the accuracy of the diffusion measurements. The alkyne reactant diffuses slower as the reaction proceeds due to binding to the copper catalyst during the catalytic cycle. The formation of this intermediate was confirmed by complementary NMR techniques and density functional theory calculations. Our work calls into question recent claims that molecules actively propel or swim during reactions and establishes that time-resolved diffusion NMR measurements can provide valuable insight into reaction mechanisms.

Diffusion coefficient analysis method using data statistical processing to reduce interference fringe noise effects

AbstractWe proposed a simple statistical analysis method of minute concentration changes for measuring diffusion coefficient with reduced interference fringe noise effect. In the “Soret‐Facet Mission,” the one‐dimensional diffusion equation discretized by the finite difference method was applied for temporal homogenization processes of the minute concentration gradient induced by the Soret effect with random noises. Measured diffusion coefficient Dexp was determined by evaluating the obtained apparent diffusion coefficient distributions D. The measured value Dexp obtained by the proposed processes was found to be valid because the measured value Dexp was close to the theoretical one Dth calculated by the Darken equation and the reference one Dref calculated in” Facet Mission” in the same solution system, respectively. In addition, by analyzing about 1/16th of the total field of view, it was possible to obtain a diffusion coefficient that are more than 95% convergent for the measured value Dexp obtained from the full field of view analysis.

Synergistic Properties of Arabinogalactan (AG) and Hyaluronic Acid (HA) Sodium Salt Mixtures.

The properties of mixtures of two polysaccharides, arabinogalactan (AG) and hyaluronic acid (HA), were investigated in solution by the measurement of diffusion coefficients D of water protons by DOSY (Diffusion Ordered SpectroscopY), by the determination of viscosity and by the investigation of the affinity of a small molecule molecular probe versus AG/HA mixtures in the presence of bovine submaxillary mucin (BSM) by 1HNMR spectroscopy. Enhanced mucoadhesive properties, decreased mobility of water and decreased viscosity were observed at the increase of AG/HA ratio and of total concentration of AG. This unusual combination of properties can lead to more effective and long-lasting hydration of certain tissues (inflamed skin, dry eye corneal surface, etc.) and can be useful in the preparation of new formulations of cosmetics and of drug release systems, with the advantage of reducing the viscosity of the solutions.

Repeatability and Reproducibility of ADC Measurements and MRI Signal Intensity Measurements of Bone Marrow in Monoclonal Plasma Cell Disorders: A Prospective Bi-institutional Multiscanner, Multiprotocol Study.

Apparent diffusion coefficient (ADC) and signal intensity (SI) measurements play an increasing role in magnetic resonance imaging (MRI) of monoclonal plasma cell disorders. The purpose of this study was to assess interrater variability, repeatability, and reproducibility of ADC and SI measurements from bone marrow (BM) under variation of MRI protocols and scanners. Fifty-five patients with suspected or confirmed monoclonal plasma cell disorder were prospectively included in this institutional review board-approved study and underwent several measurements after the standard clinical whole-body MR scan, including repeated scan after repositioning, scan with a second MRI protocol, scan at a second 1.5 T scanner with a harmonized MRI protocol, and scan at a 3 T scanner. For T1-weighted, T2-weighted STIR, B800 images, and ADC maps, regions of interest were placed in the BM of the iliac crest and sacral bone, and in muscle tissue for image normalization. Bland-Altman plots were constructed, and absolute bias, relative bias to mean, limits of agreement, and coefficients of variation were calculated. Interrater variability and repeatability experiments showed a maximal relative bias of -0.077 and a maximal coefficient of variation of 16.2% for all sequences. Although the deviations at the second 1.5 T scanner with harmonized MRI protocol to the first 1.5 T scanner showed a maximal relative bias of 0.124 for all sequences, the variation of the MRI protocol and scan at the 3 T scanner led to large relative biases of up to -0.357 and -0.526, respectively. When comparing the 3 T scanner to the 1.5 T scanner, normalization to muscle reduced the bias of T1-weighted and T2-weighted sequences, but not of ADC maps. The MRI scanners with identical field strength and harmonized MRI protocols can provide relatively stable quantitative measurements of BM ADC and SI. Deviations in MRI field strength and MRI protocol should be avoided when applying ADC cutoff values, which were established at other scanners or when performing multicentric imaging trials.

A new boundary condition forging the unprecedented self-consistence of galvanostatic intermittent titration technique

Galvanostatic Intermittent Titration Technique (GITT) is widely applied to undertake the measurement of Li ion diffusion coefficient D in solid phase of electrode materials. However, various parameters adopted in GITT lead to considerable gaps of values of D in previous researches, making the measurement less rigorous. This work tries to introduce an indicator, the first derivative of ∆Eτ (or Eτ) vs t, to sift out the start of time region for the quasi-steady state. Further, by the introduction of a new boundary condition in GITT model, an enabler based on the slope ratio of ∂E/∂t at various titration currents is developed to reveal a more appropriate time region, realizing the high self-consistence of results calculated from GITT with different parameters. Particularly, the time region for Li+ diffusion in solid phase optimized from the enabler is even several orders of magnitude later than time constants derived from equivalent circuits. Based on the optimization of time region, the calculation of D via GITT achieves an unprecedented self-consistence within different titration currents over the un-optimized one. Such optimization may set a standard for calculate ion of Li+ diffusion in electrode materials.

Plasticized 3D-Printed Polymer Electrolytes for Lithium-Ion Batteries

In the current research, we developed and printed by fused-filament fabrication polylactide-polyethylene-oxide blended membranes. The influence of relative content of polymers on the ease of extrusion and printing processes was studied. Ionic liquid N-butyl-N-methylpyrrolidinium bis(trifluoromethane-sulfonyl)imide (Pyr14TFSI) with dissolved LiTFSI salt was infused into the membranes to produce free-standing films of quasi-solid polymer electrolytes. The printed membranes were characterized by ESEM, DSC, XPS, NMR and EIS methods. Neat-printed PLA (polylactide) membrane exhibited poor wetting and low uptake of ionic liquid. However, the XPS tests of 3D-printed PLA-PEO membrane infused with LiTFSI solvated ionic liquid show evidence of the interaction between lithium cations with both, PEO (polyethylene oxide) and PLA. The measurements of diffusion coefficients by PGSE-NMR suggest that the Li+ ions are coordinated by the PEO segments in the polymer blend. Increase of the PEO content at the expense of PLA polymer, leads to more than one order of magnitude improvement of bulk conductivity, approaching 0.2 mS cm−1 at 60

Measurement of effective Sr diffusion coefficients in IG-110 graphite

Radionuclide transport and release from operating HTGR cores during normal and off-normal operations carries the possibility of increased exposure risk to reactor personnel as well as radionuclide release to the surrounding environment in the event of a depressurization accident. Diffusion is one of the primary processes by which this radionuclide transport takes place. 90Sr is one of several fission products which is commonly investigated within the context of high-temperature gas-cooled reactors due to its low volatility and ability to migrate through intact TRISO fuel particles. Effective diffusion coefficients for strontium in unirradiated IG-110 graphite have been experimentally determined over the temperature range 1773 K – 1973 K using a time-release method coupled to an inductively-coupled plasma mass spectrometer. The results of this work are: DSr,IG−110=(1.7×10−1m2/s)exp(−3.46×105J/molRT)

Convective Transport of Ce3+ in Nafion® Membrane

Proton exchange membrane fuel cells (PEMFC) are often loaded with various metal cations (Ce3+, Co2+, etc.) within the ion-conducting membrane. These proton-displacing cations can be introduced at beginning-of-life (BOL) for chemical degradation mitigation purposes or may passively accumulate over run time via Pt-alloy catalyst dissolution or other contamination sources.1 Within the proton conducting ionomer phase of the membrane electrode assembly (MEA), the metal cations ion pair with the sulfonate anions of the polymer. During operation over less than 100 hours, the metal cations are observed to migrate or redistribute on cm-length scales in the plane of the MEA. The movement of cations within the MEA plane is governed by cation charge, ionic radius, local water content (λ = n H2O/-SO3 -) and water content gradients (Δλ). Previous studies have shown that the cation isotropic concentration-gradient diffusion coefficients vary strongly with the membrane hydration level.2 The resulting redistribution of cations can have a significant impact on cell performance and mitigation of chemical degradation processes. Accordingly, there is great interest in understanding and quantifying the factors that govern cation movement to optimize fuel cell efficiency and durability.We will report the in-plane convective migration of Ce3+ and Co2+ in Nafion® membranes at 80 °C under the influence of controlled λ gradients. The cation migration studies were performed using a two-chamber RH cell as shown in Figure 1a. The test design can investigate the migration of both discreet (positions 2-4) and continuous uniform cation distributions (position 1), allowing a comprehensive understanding of the migration physics.Figure 1b depicts the convective migration of Ce3+ in Nafion® membrane (NR211, 12 mol%) over 288 hours of treatment in the two-chamber cell at 80 °C. Significant net migration of Ce3+ from the wet (95%RH) to the dry chamber (50% RH) is observed, including wet-side Ce3+ depletion and dry-side concentration. In addition to the convective migration, isotropic concentration gradient diffusion coefficient measurements were obtained from positions 3 and 4 (Figure 1a).Using the fundamental diffusion coefficients determined at various RH values, a robust 1-D transient model of the convective transport has been developed that captures experimental observations of cation migration across a wide range of membrane hydration gradients and cation concentrations. References A. Kusoglu and A. Weber, Chem Rev. 117, 987, (2017)A. M. Baker, S. K. Babu, K. Chintam, A. Kusoglu, R. Mukundan, and R. L. Borup, ECS Trans., 92 (8), 429 (2019) Figure 1. Depiction of the convective cation migration apparatus and representative data. The two-chamber device (a) accommodates four test samples that can support a range of t=0 cation distributions. Experimental 80°C time series data of a uniform 12 mol% Ce3+ Nafion® sample subjected to 95 and 50% RH in the wet and dry chambers, respectively. Figure 1

Intra- and Interobserver Variability in Magnetic Resonance Imaging Measurements in Rectal Cancer Patients.

Simple SummaryColorectal cancer is the second most common cancer and was the second most common cause of cancer-related death in Europe in 2018. Accurate lymph node staging in primary rectal cancer staging is essential for the selection of the proper treatment regimen. In 2018, The European Society of Gastrointestinal and Abdominal Radiology published consensus recommendations for primary rectal cancer staging, and suggested that lymph nodes be assessed by size, morphology, and location in- or outside the mesorectal fascia. Our study aimed to assess the inter- and intraobserver variability in size, apparent diffusion coefficient measurements, and morphological characterization among inexperienced and experienced radiologists. Our data indicate that subjective variables like morphological characteristics are less reproducible than numerical variables, regardless of the level of experience of the observers.Colorectal cancer is the second most common cancer in Europe, and accurate lymph node staging in rectal cancer patients is essential for the selection of their treatment. MRI lymph node staging is complex, and few studies have been published regarding its reproducibility. This study assesses the inter- and intraobserver variability in lymph node size, apparent diffusion coefficient (ADC) measurements, and morphological characterization among inexperienced and experienced radiologists. Four radiologists with different levels of experience in MRI rectal cancer staging analyzed 36 MRI scans of 36 patients with rectal adenocarcinoma. Inter- and intraobserver variation was calculated using interclass correlation coefficients and Cohens-kappa statistics, respectively. Inter- and intraobserver agreement for the length and width measurements was good to excellent, and for that of ADC it was fair to good. Interobserver agreement for the assessment of irregular border was moderate, heterogeneous signal was fair, round shape was fair to moderate, and extramesorectal lymph node location was moderate to almost perfect. Intraobserver agreement for the assessment of irregular border was fair to substantial, heterogeneous signal was fair to moderate, round shape was fair to moderate, and extramesorectal lymph node location was substantial to almost perfect. Our data indicate that subjective variables such as morphological characteristics are less reproducible than numerical variables, regardless of the level of experience of the observers.

Incorporating diffusion-weighted imaging in a diagnostic algorithm for multiparametric MR mammography.

Apparent diffusion coefficient (ADC) measurements are not incorporated in BI-RADS classification. To assess the probability of malignancy of breast lesions at magnetic resonance mammography (MRM) at 3 T, by combining ADC measurements with the BI-RADS score, in order to improve the specificity of MRM. A total of 296 biopsy-proven breast lesions were included in this prospective study. MRM was performed at 3 T, using a standard protocol with dynamic sequence (DCE-MRI) and an extra echo-planar diffusion-weighted sequence. A freehand region of interest was drawn inside the lesion, and ADC values were calculated. Each lesion was categorized according to the BI-RADS classification. Logistic regression analysis was employed to predict the probability of malignancy of a lesion. The model combined the BI-RADS classification and the ADC value. Sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy were calculated. In total, 153 malignant and 143 benign lesions were analyzed; 257 lesions were masses and 39 lesions were non-mass-like enhancements. The sensitivity and specificity of the combined method were 96% and 86%, respectively, in contrast to 95% and 81% with BI-RADS classification alone. We propose a method of assessing the probability of malignancy in breast lesions by combining BI-RADS score and ADC values into a single formula, increasing sensitivity and specificity compared to BI-RADS classification alone.

P-017: Repeatability and reproducibility of apparent diffusion coefficient measurements of bone marrow in magnetic resonance imaging of multiple myeloma patients

<h3>Introduciton</h3> Diffusion weighed imaging (DWI) within whole-body magnetic resonance imaging (wb-MRI) is now recommended for imaging of patients with monoclonal plasma cell disorders, and quantitative ADC measurements are of high relevance for reading and reporting of wb-MRIs. However, the evidence on repeatability and especially on multicentric reproducibility of ADC measurements of the bone marrow (BM) is very limited. The goal of this study was to quantify interrater-variability, repeatability and reproducibility of ADC measurements under variation of MRI scanners and MRI sequences. <h3>Methods</h3> Fifty-five patients were prospectively included in this IRB-approved prospective study and underwent multiple scans in different settings within a maximum of 3 days between the scans. A standard scan (clinical 1.5T-MRI scanner, standard MRI-protocol) of the pelvic bone marrow was performed. Additionally, several measurements were performed: First, a retest after new positioning of the patient (same 1.5T scanner, same protocol, i.e., repeatability; n=37 paired scans). Second, retest at the same scanner but with different MRI protocol (n=37 paired scans). Third, retest at another 1.5T scanner with a harmonized MRI protocol to the initial setting (n=34 paired scans). Fourth, retest at another scanner with different field strength of 3T (n=40 paired scans). For measurement of ADC, one radiologist manually placed regions of interest (ROI) in a representative area of BM at the posterior iliac crest and a ROI in representative muscle tissue in the same slice. A second rater independently performed a second read of the standard scan. The Bland-Altman-approach was used to assess agreement of the different settings and mean bias, limits of agreement (LoA) and coefficients of variation (CoV) were calculated. <h3>Results</h3> Absolute bias / relative bias to mean / CoV of ADC measurements for the different retest measurements compared to the standard-scan were as follows: interrater setting -37.9mm² s^-1/-0.077/15.8%, repeatability -13.0mm² s^-1/-0.027/14.5%, second protocol -205.1mm² s^-1/-0.357/33.5%, second 1.5T scanner 5.8mm² s^-1/0.013/17.0%, 3T scanner 146.8mm² s^-1/0.371/41.3%. Normalization to muscle tissue did not improve the high relative bias of the second protocol or the 3T scanner to the standard setting. <h3>Conclusion</h3> In this study we quantified interrater-variability, repeatability and reproducibility of BM ADC measurements in repeated scans after patient repositioning, different protocols, different MRI scanners and different radiologists. Bias and CoV between two different 1.5T MRI scanners with harmonized protocols were in the range of interrater-variability and repeatability. On the contrary, variation of MRI protocols and field strength of the MRI scanner led to marked bias between ADC-measurements which could not be solved by normalization to muscle tissue. These findings are of high importance for planning of multicentric imaging studies in myeloma.

Interactions between PAMAM-NH2 and 6-Mercaptopurine: Qualitative and Quantitative NMR studies.

Despite being used as an anti-leukemic drug, the poor solubility of 6-mercaptopurine (6-MP) limits its use in topical and parenteral applications. Dendrimers are commonly used as drug carriers to improve their solubility in aqueous solution. In this work, the interactions between 6-MP and the amine-terminated poly(amidoamine) dendrimers (PAMAM-NH2 ) were investigated by various NMR technology. The chemical shift titrations disclosed that the 6-MP interacted with the surface of PAMAM-NH2 mainly through electrostatics. The determination of diffusion coefficient and relaxation measurements further confirmed the presence of interactions in 6-MP/PAMAM-NH2 complexes. In addition, the encapsulation of 6-MP within the cavity of PAMAM-NH2 was revealed through nuclear Overhauser effect spectroscopy and Saturation Transfer Double Difference analysis. Finally, the binding strength (H-8 is 100% and H-2 is 70%) of 6-MP to PAMAM-NH2 was quantitatively expressed using epitope maps. This study provides a systematic methodology for qualitative and quantitative studies of the interactions between dendrimers and drug molecules in general.

Whole brain in vivo neuropathology: Imaging site-specific changes in brain structure over time following trimethyltin exposure in rats

Presented is a diffusion weighted imaging protocol with measures of apparent diffusion coefficient which when registered to a 3D MRI rat brain atlas provides site-specific information on 173 different brain areas. This protocol coined “in vivo neuropathology” was used to follow the progressive neurotoxic effects of trimethyltin on global gray matter microarchitecture. Four rats were given an IP injection of 7 mg/kg of the neurotoxin trimethyltin and imaged for changes in water diffusivity at 3- and 7-days post injections. At 3 days, there was a significant decrease in apparent diffusion coefficient, a proxy for cytotoxic edema, in several cortical areas and cerebellum. At 7 days the level of injury expanded to include most of the cerebral cortex, hippocampus, olfactory system, and cerebellum/brainstem corroborating much of the work done with traditional histopathology. Analysis is achieved with a minimum number of rats adhering to the laws and regulations around the humane care and use of laboratory animals, providing an alternative to the traditional tests for assessing drug neurotoxicity. “In vivo neuropathology” can minimize the cost, expedite the process, and identify subtle changes in site-specific brain microarchitecture across the entire brain.