Structural and functional dissection of reovirus capsid folding and assembly by the prefoldin-TRiC/CCT chaperone network.

Intracellular protein homeostasis is maintained by a network of chaperones that function to fold proteins into their native conformation. The eukaryotic TRiC chaperonin (TCP1-ring complex, also called CCT for cytosolic chaperonin containing TCP1) facilitates folding of a subset of proteins with folding constraints such as complex topologies. To better understand the mechanism of TRiC folding, we investigated the biogenesis of an obligate TRiC substrate, the reovirus σ3 capsid protein. We discovered that the σ3 protein interacts with a network of chaperones, including TRiC and prefoldin. Using a combination of cryoelectron microscopy, cross-linking mass spectrometry, and biochemical approaches, we establish functions for TRiC and prefoldin in folding σ3 and promoting its assembly into higher-order oligomers. These studies illuminate the molecular dynamics of σ3 folding and establish a biological function for TRiC in virus assembly. In addition, our findings provide structural and functional insight into the mechanism by which TRiC and prefoldin participate in the assembly of protein complexes.

Metabolic activity diffusion imaging (MADI): I. Metabolic, cytometric modeling and simulations.

Evidence mounts that the steady-state cellular water efflux (unidirectional) first-order rate constant (kio [s-1 ]) magnitude reflects the ongoing, cellular metabolic rate of the cytolemmal Na+ , K+ -ATPase (NKA), c MRNKA (pmol [ATP consumed by NKA]/s/cell), perhaps biology's most vital enzyme. Optimal 1 H2 O MR kio determinations require paramagnetic contrast agents (CAs) in model systems. However, results suggest that the homeostatic metabolic kio biomarker magnitude in vivo is often too large to be reached with allowable or possible CA living tissue distributions. Thus, we seek a noninvasive (CA-free) method to determine kio in vivo. Because membrane water permeability has long been considered important in tissue water diffusion, we turn to the well-known diffusion-weighted MRI (DWI) modality. To analyze the diffusion tensor magnitude, we use a parsimoniously primitive model featuring Monte Carlo simulations of water diffusion in virtual ensembles comprising water-filled and -immersed randomly sized/shaped contracted Voronoi cells. We find this requires two additional, cytometric properties: the mean cell volume (V [pL]) and the cell number density (ρ [cells/µL]), important biomarkers in their own right. We call this approach metabolic activity diffusion imaging (MADI). We simulate water molecule displacements and transverse MR signal decays covering the entirety of b-space from pure water (ρ = V = 0; kio undefined; diffusion coefficient, D0 ) to zero diffusion. The MADI model confirms that, in compartmented spaces with semipermeable boundaries, diffusion cannot be described as Gaussian: the nanoscopic D (Dn ) is diffusion time-dependent, a manifestation of the "diffusion dispersion". When the "well-mixed" (steady-state) condition is reached, diffusion becomes limited, mainly by the probabilities of (1) encountering (ρ, V), and (2) permeating (kio ) cytoplasmic membranes, and less so by Dn magnitudes. Importantly, for spaces with large area/volume (A/V; claustrophobia) ratios, this can happen in less than a millisecond. The model matches literature experimental data well, with implications for DWI interpretations.

Metabolic activity diffusion imaging (MADI): II. Noninvasive, high-resolution human brain mapping of sodium pump flux and cell metrics.

We introduce a new 1 H2 O magnetic resonance approach: metabolic activity diffusion imaging (MADI). Numerical diffusion-weighted imaging decay simulations characterized by the mean cellular water efflux (unidirectional) rate constant (kio ), mean cell volume (V), and cell number density (ρ) are produced from Monte Carlo random walks in virtual stochastically sized/shaped cell ensembles. Because of active steady-state trans-membrane water cycling (AWC), kio reflects the cytolemmal Na+ , K+ ATPase (NKA) homeostatic cellular metabolic rate (c MRNKA ). A digital 3D "library" contains thousands of simulated single diffusion-encoded (SDE) decays. Library entries match well with disparate, animal, and human experimental SDE decays. The V and ρ values are consistent with estimates from pertinent in vitro cytometric and ex vivo histopathological literature: in vivo V and ρ values were previously unavailable. The library allows noniterative pixel-by-pixel experimental SDE decay library matchings that can be used to advantage. They yield proof-of-concept MADI parametric mappings of the awake, resting human brain. These reflect the tissue morphology seen in conventional MRI. While V is larger in gray matter (GM) than in white matter (WM), the reverse is true for ρ. Many brain structures have kio values too large for current, invasive methods. For example, the median WM kio is 22s-1 ; likely reflecting mostly exchange within myelin. The kio •V product map displays brain tissue c MRNKA variation. The GM activity correlates, quantitatively and qualitatively, with the analogous resting-state brain 18 FDG-PET tissue glucose consumption rate (t MRglucose ) map; but noninvasively, with higher spatial resolution, and no pharmacokinetic requirement. The cortex, thalamus, putamen, and caudate exhibit elevated metabolic activity. MADI accuracy and precision are assessed. The results are contextualized with literature overall homeostatic brain glucose consumption and ATP production/consumption measures. The MADI/PET results suggest different GM and WM metabolic pathways. Preliminary human prostate results are also presented.

Efficacy of Whole-Blood Model of Gadolinium-Based Contrast Agent Relaxivity in Predicting Vascular MR Signal Intensity In Vivo.

BACKGROUND: Previous in vitro studies have described sub-linear longitudinal and heightened transverse H2 O relaxivities of gadolinium-based contrast agents (GBCAs) in blood due to their extracellular nature. However, in vivo validation is lacking. PURPOSE: Validate theory describing blood behavior of R1 and R2 * in an animal model. STUDY TYPE: Prospective, animal. ANIMAL MODEL: Seven swine (54-65 kg). FIELD STRENGTH/SEQUENCE: 1.5 T; time-resolved 3D spoiled gradient-recalled echo (SPGR) and quantitative Look-Locker and multi-echo fast field echo sequences. ASSESSMENT: Seven swine were each injected three times with 0.1 mmol/kg intravenous doses of one of three GBCAs: gadoteridol, gadobutrol, and gadobenate dimeglumine. Injections were randomized for rate (1, 2, and 3 mL/s) and order, during which time-resolved aortic 3D SPGR imaging was performed concurrently with aortic blood sampling via an indwelling catheter. Time-varying [GBCA] was measured by mass spectrometry of sampled blood. Predicted signal intensity (SI) was determined from a model incorporating sub-linear R1 and R2 * effects (whole-blood model) and simpler models incorporating linear R1 , with and without R2 * effects. Predicted SIs were compared to measured aortic SI. STATISTICAL TESTS: Linear correlation (coefficient of determination, R2 ) and mean errors were compared across the SI prediction models. RESULTS: There was an excellent correlation between predicted and measured SI across all injections and swine when accounting for the non-linear dependence of R1 and high blood R2 * (regression slopes 0.91-1.04, R2 ≥ 0.91). Simplified models (linear R1 with and without R2 * effects) showed poorer correlation (slopes 0.67-0.85 and 0.54-0.64 respectively, both R2 ≥ 0.89) and higher averaged mean absolute and mean square errors (128.4 and 177.4 vs. 42.0, respectively, and 5506 and 11,419 vs. 699, respectively). DATA CONCLUSION: Incorporating sub-linear R1 and high first-pass R2 * effects in arterial blood models allows accurate SPGR SI prediction in an in vivo animal model, and might be utilized when modeling MR blood SI. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 1.

Relationship Between Simulated Gadolinium-Based Contrast Agent Injection Profile and Achievable Resolution Metrics in Contrast-Enhanced Magnetic Resonance Angiography.

BACKGROUND: Contrast bolus variation during contrast-enhanced magnetic resonance angiography (CE-MRA) acquisition may lead to vessel blurring. PURPOSE: To combine knowledge of how contrast signal intensity (SI) evolves for different injection strategies with anatomically familiar parametric computer models to measure and visually assess the effects of a wide range of variables on modeled CE-MRA, and in doing so develop contrast rate injection guidelines. STUDY TYPE: Computer modeling. PHANTOM: Digital three-dimensional phantom consisting of orthogonal "aorta," 7 mm diameter "renal arteries" (with 57% and 86% diameter stenoses), and 7 mm diameter "superior mesenteric artery" (with 57% diameter stenosis). FIELD STRENGTH/SEQUENCE: One millimeter in-plane resolution arterial CE-MRA imaging at 3 T. ASSESSMENT: "Background" (time invariant) and "vascular" (time varying) components of the phantom were each Fourier transformed into the spatial frequency domain, the latter modulated by the SI evolution of a contrast bolus of varying "plateau" lengths and "tail" heights. Data are presented as surface plots of stenosis measurement error and blurring vs. a reference-standard injection. STATISTICAL TESTS: Descriptive. RESULTS: Shorter plateau lengths and lower tail heights resulted in increased measured stenosis error and blurring vs. the reference standard. Under a 44-second acquisition, full width half maximum stenosis error of the 86% stenosis with 25% plateau length and 25% tail height is 24% as compared to that from the reference standard. As plateau length and tail height approach 100%, stenosis error and blurring approach a floor defined by the MR acquisition's limitations. DATA CONCLUSION: We propose that to achieve minimal degradation with CE-MRA, one can create a contrast bolus with either 60% plateau and 50% tail height or 80% plateau with any tail. These considerations may well prove to be of practical importance, possibly via manipulating the tail by means of multiphasic contrast injections. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 1.

Strategically Constructed Bilayer Tin (IV) Oxide as Electron Transport Layer Boosts Performance and Reduces Hysteresis in Perovskite Solar Cells.

Nanostructured tin (IV) oxide (SnO2 ) is emerging as an ideal inorganic electron transport layer in n-i-p perovskite devices, due to superior electronic and low-temperature processing properties. However, significant differences in current-voltage performance and hysteresis phenomena arise as a result of the chosen fabrication technique. This indicates enormous scope to optimize the electron transport layer (ETL), however, to date the understanding of the origin of these phenomena is lacking. Reported here is a first comparison of two common SnO2 ETLs with contrasting performance and hysteresis phenomena, with an experimental strategy to combine the beneficial properties in a bilayer ETL architecture. In doing so, this is demonstrated to eliminate room-temperature hysteresis while simultaneously attaining impressive power conversion efficiency (PCE) greater than 20%. This approach highlights a new way to design custom ETLs using functional thin-film coatings of nanomaterials with optimized characteristics for stable, efficient, perovskite solar cells.

Evaluation of four injection profiles for uniform contrast-enhanced signal intensity profiles in MR angiography.

BACKGROUND: Gadolinium concentration variation during acquisition of contrast-enhanced MR angiography (CE-MRA) may lead to artifacts. PURPOSE: To compare signal intensity (SI) profiles of four different contrast agent injection strategies during CE-MRA with the goal of minimizing SI variation during acquisition. STUDY TYPE: Prospective. SUBJECTS: Forty subjects randomized to receive one of four injection profiles of gadobenate dimeglumine (0.1 mmol/kg), either undiluted (0.5 M) or diluted to 40 ml total volume. Tested profiles: 1) nondiluted single-phase ("standard" NS; 1.6 ml/s), 2) diluted single-phase (DS; 1.6 ml/s), 3) diluted biphasic (DB; 9 ml @ 3.3 ml/s, 29 ml @ 1.4 ml/s), 4) patient-tailored protocol using linear prediction (DT). FIELD STRENGTH/SEQUENCE: Time-resolved SI measured at 3T with spoiled gradient echo sequences having analogous parameters to those of CE-MRA. ASSESSMENT: Plateau arrival time, rise time, duration, peak and tail SI, plateau quality (sum of squared residuals; SSR), average SI for each injection type derived were used. STATISTICAL TEST: Two-tailed t-test. RESULTS: Peak SI, arrival, and rise times were not significantly different between groups, excepting peak SI DB slightly > DS (P = 0.042). Duration of NS vs. the diluted groups was significantly shorter (all P < 0.0001), and DS duration was significantly shorter than that of DT and DB (NS 11.4 ± 3.5 vs. DS 22.9 ± 4.3, DB 25.4 ± 2.3, DT 28.3 ± 4.1 sec). Quality (SSR) of the 20-second plateau was significantly better for DS, DB, DT as compared with NS (all P < 0.001). DATA CONCLUSION: Three different strategies to power-inject diluted gadobenate dimeglumine targeting a 20-second plateau produced SI profiles with longer duration, more consistent plateau, and no significant loss in peak SI. Such injection profiles may provide more uniform SI during CE-MRA, potentially reducing blurring artifacts. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;50:1808-1816.

Long-term outcomes of patients with end-stage kidney disease due to membranoproliferative glomerulonephritis: an ANZDATA registry study.

BACKGROUND: Membranoproliferative glomerulonephritis (MPGN) is an uncommon cause of end stage kidney disease (ESKD) and the clinical outcomes of patients with MPGN who commence kidney replacement therapy have not been comprehensively studied. METHODS: All adult patients with ESKD due to glomerulonephritis commencing kidney replacement therapy in Australia and New Zealand from January 1, 1996 to December 31, 2016 were reviewed. Patients with ESKD due to MPGN were compared to patients with other forms of glomerulonephritis. Patient survival on dialysis and following kidney transplantation, kidney recovery on dialysis, time to transplantation, allograft survival, death-censored allograft survival and disease recurrence post-transplant were compared between the two groups using Kaplan Meier survival curves and Cox proportional hazards regression. RESULTS: Of 56,481 patients included, 456 (0.8%) had MPGN and 12,660 (22.4%) had another form of glomerulonephritis. Five-year patient survival on dialysis and following kidney transplantation were similar between patients with ESKD from MPGN and other forms of glomerulonephritis (Dialysis: 59% vs. 62% p = 0.61; Transplant: 93% vs. 93%, p = 0.49). Compared to patients with other forms of glomerulonephritis, patients with MPGN had significantly poorer 5-year allograft survival (70% vs. 81% respectively, p = 0.02) and death censored allograft survival (74% vs. 87%, respectively; p < 0.01). The risk of disease recurrence was significantly higher in patients with MPGN compared to patients with other glomerulonephritidites (18% vs. 5%; p < 0.01). In patients with MPGN who had allograft loss, patients with MPGN recurrence had a significantly shorter time to allograft loss compared to patients with MPGN who had allograft loss due to any other cause (median time to allograft loss 3.2 years vs. 4.4 years, p < 0.01). CONCLUSIONS: Compared with other forms of glomerulonephritis, patients with MPGN experienced comparable rates of survival on dialysis and following kidney transplantation, but significantly higher rates of allograft loss due to disease recurrence.

Initial Clinical Experience with Dual-Agent Relaxation Contrast for Isolated Lymphatic Channel Mapping.

Purpose To evaluate the clinical performance of dual-agent relaxation contrast (DARC) magnetic resonance (MR) lymphangiography compared with that of conventional MR lymphangiography in the creation of isolated lymphatic maps in patients with secondary lymphedema. Materials and Methods This retrospective study was approved by the institutional review board. The diagnostic quality of 42 DARC MR lymphangiographic studies was compared with that of 42 conventional MR lymphangiographic studies. Two independent readers rated venous contamination as absent, mild, or moderate to severe. Interreader agreement on venous contamination grades was assessed by using the linearly weighted Cohen κ statistic. The Mann-Whitney U test was used to compare the distribution of grades at each station between conventional MR lymphangiography and DARC MR lymphangiography for each reader separately. Results DARC MR lymphangiography had significantly less venous contamination than did conventional MR lymphangiography (P < .001). The two radiologists rated venous contamination as moderate to severe in 64% (27 of 42) and 69% (29 of 42) of distal limbs, 23% (10 of 42) of midlimbs, and 2% (one of 42) and 9% (four of 42) of proximal limbs at conventional MR lymphangiography compared with 0% (0 of 42) of distal limbs, 2% (one of 42) of midlimbs, and 0% (0 of 42) of proximal limbs at DARC MR lymphangiography. Lymphatic signal was partially attenuated (median 45% decrease) when longer echo times were used for venous suppression, but it did not subjectively degrade diagnostic quality. Conclusion DARC MR lymphangiography yields isolated lymphatic maps through nulling of venous contamination, thereby simplifying diagnostic interpretation and communication with surgical colleagues. © RSNA, 2017.

Clinical utility of endomyocardial biopsies in the diagnosis of arrhythmogenic right ventricular cardiomyopathy in children.

BACKGROUND: Histomorphometry of endomyocardial biopsies is one component of arrhythmogenic right ventricular cardiomyopathy (ARVC) diagnosis, although there is a need for stricter diagnostic criteria for this disease in pediatrics. The clinical utility of biopsy analysis as a component of ARVC diagnosis was evaluated in pediatric patients. METHODS: Histomorphometric analysis of fibrofatty infiltrate was completed on pediatric right ventricular endomyocardial biopsy samples. Myocardial replacement by fat and fibrosis was quantified. ARVC diagnosis was established using the 2010 ARVC Task Force criteria, with the biopsy measures compared across various ARVC diagnoses (definite, borderline, possible, or no ARVC). Receiver-operating characteristic (ROC) curve analysis was also completed using biopsy measures. RESULTS: The greatest proportion of fat, fibrosis, and myocardial replacement was in the definite ARVC cohort, and was significantly larger than for the other diagnosis cohorts. ROC curve analysis (with the biopsy analysis removed from the diagnostic classification) produced cutoff values of 15 and 25% myocardial replacement, which is lower than current adult diagnosis criteria. CONCLUSION: We propose modifications in pediatric major and minor biopsy diagnosis criteria to allow for improved sensitivity. This study suggests that biopsy analysis in children is most significant for subjects with a more severe disease presentation.

3D true-phase polarity recovery with independent phase estimation using three-tier stacks based region growing (3D-TRIPS).

OBJECTIVES: A postprocessing technique termed 3D true-phase polarity recovery with independent phase estimation using three-tier stacks based region growing (3D-TRIPS) was developed, which directly reconstructs phase-sensitive inversion-recovery images without acquisition of phase-reference images. The utility of this technique is demonstrated in myocardial late gadolinium enhancement (LGE) imaging. MATERIALS AND METHODS: A data structure with three tiers of stacks was used for 3D-TRIPS to directly achieve reliable region growing for successful background-phase estimation. Fifteen patients undergoing postgadolinium 3D phase-sensitive inversion recovery (PSIR) cardiac LGE magnetic resonance imaging (MRI) were recruited, and 3D-TRIPS LGE reconstructions were compared with standard PSIR. Objective voxel-by-voxel comparison was performed. Additionally, blinded review by two radiologists compared scar visibility, clinical acceptability, voxel polarity error, or groups and blurring. RESULTS: 3D-TRIPS efficiently reconstructed postcontrast phase-sensitive myocardial LGE images. Objective analysis showed an average 95% voxel-by-voxel agreement between 3D-TRIPS and PSIR images. Blinded radiologist review demonstrated similar image quality between 3D-TRIPS and PSIR reconstruction. CONCLUSION: 3D-TRIPS provided similar image quality to PSIR for phase-sensitive myocardial LGE MRI reconstruction. 3D-TRIPS does not require acquisition of a reference image and can therefore be used to accelerate phase-sensitive LGE imaging.

Human whole blood 1 H2 O transverse relaxation with gadolinium-based contrast reagents: Magnetic susceptibility and transmembrane water exchange.

PURPOSE: To characterize transverse relaxation in oxygenated whole blood with extracellular gadolinium-based contrast reagents by experiment and simulation. METHODS: Experimental measurements of transverse 1 H2 O relaxation from oxygenated whole human blood and plasma were made at 1.5 and 3.0 Tesla. Spin-echo refocused and free-induction decays are reported for blood and plasma samples containing four different contrast reagents (gadobenate, gadoteridol, gadofosveset, and gadobutrol), each present at concentrations ranging from 1 to 18 mM (i.e., mmol (contrast reagent (CR))/L (blood)). Monte Carlo simulations were conducted to ascertain the molecular mechanisms underlying relaxation. These consisted of random walks of water molecules in a large ensemble of randomly oriented erythrocytes. Bulk magnetic susceptibility (BMS) differences between the extra- and intracellular compartments were taken into account. All key parameters for these simulations were taken from independent published measurements: they include no adjustable variables. RESULTS: Transverse relaxation is much more rapid in whole blood than in plasma, and the large majority of this dephasing is reversible by spin echo. Agreement between the experimental data and simulated results is remarkably good. CONCLUSION: Extracellular field inhomogeneities alone make very small contributions, whereas the orientation-dependent BMS intracellular resonance frequencies lead to the majority of transverse dephasing. Equilibrium exchange of water molecules between the intra- and extracellular compartments plays a significant role in transverse dephasing. Magn Reson Med 77:2015-2027, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Effect of injection rate on contrast-enhanced MR angiography image quality: Modulation transfer function analysis.

PURPOSE: Contrast-enhanced (CE)-MRA optimization involves interactions of sequence duration, bolus timing, contrast recirculation, and both R1 relaxivity and R2*-related reduction of signal. Prior data suggest superior image quality with slower gadolinium injection rates than typically used. METHODS: A computer-based model of CE-MRA was developed, with contrast injection, physiologic, and image acquisition parameters varied over a wide gamut. Gadolinium concentration was derived using Verhoeven's model with recirculation, R1 and R2* calculated at each time point, and modulation transfer curves used to determine injection rates, resulting in optimal resolution and image contrast for renal and carotid artery CE-MRA. Validation was via a vessel stenosis phantom and example patients who underwent carotid CE-MRA with low effective injection rates. RESULTS: Optimal resolution for renal and carotid CE-MRA is achieved with injection rates between 0.5 to 0.9 mL/s and 0.2 to 0.3 mL/s, respectively, dependent on contrast volume. Optimal image contrast requires slightly faster injection rates. Expected signal-to-noise ratio varies with both contrast volume and cardiac output. Simulated vessel phantom and clinical carotid CE-MRA exams at an effective contrast injection rate of 0.4 to 0.5 mL/s demonstrate increased resolution. CONCLUSION: Optimal image resolution is achieved at intuitively low, effective injection rates (0.2-0.9 mL/s, dependent on imaging parameters and contrast injection volume). Magn Reson Med 78:357-369, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

3D printing from MRI Data: Harnessing strengths and minimizing weaknesses.

3D printing facilitates the creation of accurate physical models of patient-specific anatomy from medical imaging datasets. While the majority of models to date are created from computed tomography (CT) data, there is increasing interest in creating models from other datasets, such as ultrasound and magnetic resonance imaging (MRI). MRI, in particular, holds great potential for 3D printing, given its excellent tissue characterization and lack of ionizing radiation. There are, however, challenges to 3D printing from MRI data as well. Here we review the basics of 3D printing, explore the current strengths and weaknesses of printing from MRI data as they pertain to model accuracy, and discuss considerations in the design of MRI sequences for 3D printing. Finally, we explore the future of 3D printing and MRI, including creative applications and new materials. LEVEL OF EVIDENCE: 5 J. Magn. Reson. Imaging 2017;45:635-645.

Sudden death in a pediatric heart transplant recipient with peripheral eosinophilia and eosinophilic myocardial infiltrates.

Eosinophilia has been rarely reported in pediatric heart transplant recipients and has been suggested to play a role in graft rejection. We report a case of a young female patient with peripheral blood eosinophilia who died suddenly 2 years following ABO-incompatible heart transplantation. She was found at autopsy to have myocardial infiltration of not only T-lymphocytes and macrophages expected in acute cellular rejection but also of eosinophils, B-lymphocytes, and plasma cells indicating myocarditis.

The increasing rates of acute interstitial nephritis in Australia: a single centre case series.

BACKGROUND: The Australian Institute of Health and Welfare's first report into acute kidney injury demonstrated a significant increase in the incidence of acute-tubulo interstitial nephritis, the ICD-10 code representing both acute interstitial nephritis and pyelonephritis, in women aged less than 55 years. In contrast, recent case series have reported rising rates of drug induced acute interstitial nephritis predominantly among elderly patients. Due to several limitations with the Australian Institute of Health and Welfare report, this new trend requires further investigation to determine if rates of acute interstitial nephritis are truly increasing among younger Australian women. METHODS: Patients who underwent a renal biopsy at a single center from 2000 to 2015 were reviewed and those with biopsy confirmed acute interstitial nephritis were selected. Cause of acute interstitial nephritis, patient demographics, co-morbidities and renal indices for these patients when available were recorded and compared. RESULTS: Eight hundred ninety-eight patients who underwent renal biopsy from 2000 to 2015 were reviewed and 40 patients were identified with biopsy confirmed acute interstitial nephritis. The rate of acute interstitial nephritis increased significantly over the study period (4 patients/2.2% of biopsies performed in 2000-03 vs. 19 patients/6.7% of all biopsies performed in 2012-15; p = 0.002). There was a marked increase in the number of women with AIN in the last four years of the study (2 patients and 2.1% of biopsies performed in women in 2000-2003 compared with 13 patients and 9.0% of biopsies performed in women in 2012-2015). Immune mediated causes of acute interstitial nephritis and NSAID associated AIN were more common in women (9 females vs. 3 males), occurred more frequently in the last eight years of the study and predominantly in patients under 55 years of age. CONCLUSIONS: Our study demonstrates a significant increase in the number of patients with biopsy confirmed AIN. Also, we provide preliminary evidence in support of an increase in rates of younger women with immune mediated acute interstitial nephritis. These results support the findings of the Australian Institute of Health and Welfare and suggest that younger women may be at higher risk of immune mediated and NSAID associated acute interstitial nephritis.

Evaluation of a tailored injection profile (TIP) algorithm for uniform contrast-enhanced signal intensity profiles in MR angiography.

PURPOSE: To evaluate a contrast agent injection method that provides constant magnetic resonance imaging (MRI) signal intensity throughout a contrast-enhanced MR angiography acquisition. MATERIALS AND METHODS: A tailored injection profile (TIP) algorithm was developed that used the signal intensity profile from a test bolus as an impulse response function, and predicted the response to various multiphasic injection profiles. Antecubital vein injections were administered via a commercially available multiphasic power injector. The TIP algorithm evaluated the predicted responses and selected the injection that best matched the desired (20-sec plateau) profile. Resulting signal intensity profiles from tailored and standard injection profiles were compared in 20 subjects (10 each). All subjects received a weight-based single-dose (0.1 mmol/kg) of gadoteridol, and abdominal aorta signal intensities were measured at 3T with a time-resolved, thick-slice, 3D spoiled-gradient-echo MR sequence with parameters approximating contrast-enhanced MR angiography. The single-phase, standard injection was injected at 1.6 mL/sec. RESULTS: Full-width at 80% maximum (FW80M) signal intensity was significantly longer for the tailored injection profiles (23.0 ± 2.2 vs. 9.0 ± 4.2 sec; P < 0.01). Concurrently, the profile peak signal intensity was reduced by 19% for the tailored profiles (12.0 ± 3.1 vs. 14.8 ± 2.8 times baseline; P = 0.058), nearly reaching significance. CONCLUSION: Multiphasic tailored injections from a power injector produced longer signal intensity profiles (156% increase in FW80M) with an accompanying decrease (19%) in peak signal intensity compared to a standard, single-phase injection. J. Magn. Reson. Imaging 2016. J. Magn. Reson. Imaging 2016;44:1664-1672.

Patient-specific timing for bolus-chase peripheral MR angiography.

PURPOSE: To develop a timing algorithm for three-station moving-table MR angiography of the peripheral arteries (pMRA) based on individual patient hemodynamics that optimizes arterial opacification and minimizes venous enhancement. METHODS: Two separate patient cohorts were identified for this retrospective study. The first consisted of 71 patients for development of a patient specific timing algorithm to calculate multiple contrast agent bolus transit times at 1.5 Tesla using a spoiled gradient echo sequence. This timing data was applied to a separate group of 59 patients in which one of four predetermined pMRA protocols was performed based on a time-resolved MRA of the calves. Image quality was evaluated by two blinded readers grading venous enhancement and arterial opacification. RESULTS: Transit time from abdominal aorta to foot (Ao-F) ranged from 5-46 s, with a mean of 17.8 ± 8.2 s. Arteriovenous window (AVW) transit time ranged from -5 to 65 s, with a mean of 18.3 ± 16.0 s. Ischemic patients had longer injection site-to-arterial transit times (25.6 versus 20.7 s; P < 0.01). Of the 59 patients who underwent diagnostic pMRA, 81 and 83% (two readers, respectively) showed no or minimal venous enhancement, and all of the exams were diagnostic. Venous enhancement grades were significantly greater (P < 0.04) for ischemic versus nonischemic patients. CONCLUSION: Performing pMRA using a timing algorithm based on each patient's unique hemodynamics can minimize lower station venous enhancement.

MR lymphangiography: How i do it.

Lymphedema is a chronic progressive edematous disease that in the United States is most commonly related to malignancy and its treatment. Lymphaticovenular anastomosis is a recently introduced microsurgical treatment option for lymphedema that requires the identification and mapping of individual lymphatic channels. While nuclear medicine lymphoscintigraphy has been the primary imaging modality performed to evaluate suspected lymphedema, lymphoscintigraphy does not provide the spatial information necessary for presurgical planning. High-resolution dynamic 3D magnetic resonance imaging (MRI) can noninvasively image abnormal lymphatic channels to both diagnose lymphedema and depict the location and number of individual lymphatic channels for surgical planning. MR lymphangiography can be performed at 1.5T or 3.0T using multichannel phased array surface coils. The main components of the exam are a heavily T2 -weighted 3D sequence to define the severity and extent of edema, a high-resolution dynamic 3D gradient echo imaging after intracutaneous contrast injection to visualize lymphatic channels, and a delayed 3D gradient echo sequence after intravenous contrast to define veins. This article reviews the pathophysiology and microsurgical treatment of lymphedema, presents the imaging protocol used at our institution, and describes exam interpretation and the image postprocessing performed for surgical planning.

The SYNERGY biodegradable polymer everolimus eluting coronary stent: Porcine vascular compatibility and polymer safety study.

AIMS: SYNERGY is a novel platinum chromium alloy stent that delivers abluminal everolimus from an ultrathin poly-lactide-co-glycide (PLGA) biodegradable polymer. This study evaluated the in vivo degradation of the polymer coating, everolimus release time course, and vascular compatibility of the SYNERGY stent. METHODS AND RESULTS: SYNERGY stents were implanted in arteries of domestic swine. Devices were explanted at predetermined time points (up to 120 days) and the extent of PLGA coating or everolimus remaining on the stents was quantified. Everolimus levels in the arterial tissue were also evaluated. A pathological analysis on coronary arteries of single and overlapping stents was performed at time points between 5 and 270 days. PLGA bioabsorption began immediately after implantation, and drug release was essentially complete by 90 days; PLGA absorption was substantially complete by 120 days (>90% of polymer was absorbed) leaving a bare metal SYNERGY stent. Vascular response was similar among SYNERGY and control stents (bare metal, polymer-only, and 3× polymer-only). Mild increases in para-strut fibrin were seen for SYNERGY at an early time point with no significant differences in all other morphological and morphometric parameters through 270 days or endothelial function (eNOS immunostaining) at 90 or 180 days. Inflammation was predominantly minimal to mild for all device types. CONCLUSION: In a swine model, everolimus was released by 90 days and PLGA bioabsorption was complete shortly thereafter. The SYNERGY stent and its biodegradable polymer, even at a 3× safety margin, demonstrated vascular compatibility similar to bare metal stent controls.