Maximizing SNR per unit time in diffusion MRI with multiband T-Hex spirals.

PURPOSE: The characterization of tissue microstructure using diffusion MRI (dMRI) signals is rapidly evolving, with increasing sophistication of signal representations and microstructure models. However, this progress often requires signals to be acquired with very high b-values (e.g., b > 30 ms/µm2 ), along many directions, and using multiple b-values, leading to long scan times and extremely low SNR in dMRI images. The purpose of this work is to boost the SNR efficiency of dMRI by combining three particularly efficient spatial encoding techniques and utilizing a high-performance gradient system (Gmax ≤ 300 mT/m) for efficient diffusion encoding. METHODS: Spiral readouts, multiband imaging, and sampling on tilted hexagonal grids (T-Hex) are combined and implemented on a 3T MRI system with ultra-strong gradients. Image reconstruction is performed through an iterative cg-SENSE algorithm incorporating static off-resonance distributions and field dynamics as measured with an NMR field camera. Additionally, T-Hex multiband is combined with a more conventional EPI-readout and compared with state-of-the-art blipped-CAIPIRINHA sampling. The advantage of the proposed approach is furthermore investigated for clinically available gradient performance and diffusion kurtosis imaging. RESULTS: High fidelity in vivo images with b-values up to 40 ms/µm2 are obtained. The approach provides superior SNR efficiency over other state-of-the-art multiband diffusion readout schemes. CONCLUSION: The demonstrated gains hold promise for the widespread dissemination of advanced microstructural scans, especially in clinical populations.

In vivo diffusion MRI of the human heart using a 300 mT/m gradient system.

PURPOSE: This work reports for the first time on the implementation and application of cardiac diffusion-weighted MRI on a Connectom MR scanner with a maximum gradient strength of 300 mT/m. It evaluates the benefits of the increased gradient performance for the investigation of the myocardial microstructure. METHODS: Cardiac diffusion-weighted imaging (DWI) experiments were performed on 10 healthy volunteers using a spin-echo sequence with up to second- and third-order motion compensation ( M 2 $$ {M}_2 $$ and M 3 $$ {M}_3 $$ ) and b = 100 , 450 $$ b=100,450 $$ , and 1000 s / m m 2 $$ \mathrm{s}/\mathrm{m}{\mathrm{m}}^2 $$ (twice the b max $$ {b}_{\mathrm{max}} $$ commonly used on clinical scanners). Mean diffusivity (MD), fractional anisotropy (FA), helix angle (HA), and secondary eigenvector angle (E2A) were calculated for b = [100, 450] s / m m 2 $$ \mathrm{s}/\mathrm{m}{\mathrm{m}}^2 $$ and b = [100, 1000] s / m m 2 $$ \mathrm{s}/\mathrm{m}{\mathrm{m}}^2 $$ for both M 2 $$ {M}_2 $$ and M 3 $$ {M}_3 $$ . RESULTS: The MD values with M 3 $$ {M}_3 $$ are slightly higher than with M 2 $$ {M}_2 $$ with Δ MD = 0 . 05 ± 0 . 05 [ × 1 0 - 3 mm 2 / s ] ( p = 4 e - 5 ) $$ \Delta \mathrm{MD}=0.05\pm 0.05\kern0.3em \left[\times 1{0}^{-3}\kern0.3em {\mathrm{mm}}^2/\mathrm{s}\right]\kern0.3em \left(p=4e-5\right) $$ for b max = 450 s / mm 2 $$ {b}_{\mathrm{max}}=450\kern0.3em \mathrm{s}/{\mathrm{mm}}^2 $$ and Δ MD = 0 . 03 ± 0 . 03 [ × 1 0 - 3 mm 2 / s ] ( p = 4 e - 4 ) $$ \Delta \mathrm{MD}=0.03\pm 0.03\kern0.3em \left[\times \kern0.3em 1{0}^{-3}\kern0.3em {\mathrm{mm}}^2/\mathrm{s}\right]\kern0.3em \left(p=4e-4\right) $$ for b max = 1000 s / mm 2 $$ {b}_{\mathrm{max}}=1000\kern0.3em \mathrm{s}/{\mathrm{mm}}^2 $$ . A reduction in MD is observed by increasing the b max $$ {b}_{\mathrm{max}} $$ from 450 to 1000 s / mm 2 $$ \mathrm{s}/{\mathrm{mm}}^2 $$ ( Δ MD = 0 . 06 ± 0 . 04 [ × 1 0 - 3 mm 2 / s ] ( p = 1 . 6 e - 9 ) $$ \Delta \mathrm{MD}=0.06\pm 0.04\kern0.3em \left[\times \kern0.3em 1{0}^{-3}\kern0.3em {\mathrm{mm}}^2/\mathrm{s}\right]\kern0.3em \left(p=1.6e-9\right) $$ for M 2 $$ {M}_2 $$ and Δ MD = 0 . 08 ± 0 . 05 [ × 1 0 - 3 mm 2 / s ] ( p = 1 e - 9 ) $$ \Delta \mathrm{MD}=0.08\pm 0.05\kern0.3em \left[\times \kern0.3em 1{0}^{-3}\kern0.3em {\mathrm{mm}}^2/\mathrm{s}\right]\kern0.3em \left(p=1e-9\right) $$ for M 3 $$ {M}_3 $$ ). The difference between FA, E2A, and HA was not significant in different schemes ( p > 0 . 05 $$ p>0.05 $$ ). CONCLUSION: This work demonstrates cardiac DWI in vivo with higher b-value and higher order of motion compensated diffusion gradient waveforms than is commonly used. Increasing the motion compensation order from M 2 $$ {M}_2 $$ to M 3 $$ {M}_3 $$ and the maximum b-value from 450 to 1000 s / mm 2 $$ \mathrm{s}/{\mathrm{mm}}^2 $$ affected the MD values but FA and the angular metrics (HA and E2A) remained unchanged. Our work paves the way for cardiac DWI on the next-generation MR scanners with high-performance gradient systems.

Early range of motion results in good elbow function following conservative treatment of non-displaced radial head fractures.

INTRODUCTION: The aim of this study was to evaluate the range of motion (ROM), elbow function and predictors for good elbow function after conservative treatment of non-displaced radial head fractures. MATERIAL AND METHODS: All patients with non-displaced radial head fractures (displacement < 2 mm), that were diagnosed between January 1st 2017 and December 31st 2021 in a level I trauma center, were included in this retrospective case series and the charts were evaluated for ROM and elbow function. Elbow function was categorized as "good" or "bad" depending on the ROM measured defined by Morrey et al. Overall, 73 patients (33 male, 40 female) with an average age of 38 years (+/- 13 years) could be included. RESULTS: Conservative treatment had good clinical results for ROM and elbow function. After 6 weeks mean flexion was 131° (SD 13°), extension 8° (SD 7°), Pronation 83° (SD 11°) and Supination 83° (SD 13). Patients with a good elbow function after one week showed a good elbow function after completing the treatment. CONCLUSIONS: A clinical assessment after one week should always be performed and the study showed that it is a good predictor for good elbow function. In cases of bad elbow function further controls should be considered.

In Vivo Myelin Water Quantification Using Diffusion-Relaxation Correlation MRI: A Comparison of 1D and 2D Methods.

Multidimensional Magnetic Resonance Imaging (MRI) is a versatile tool for microstructure mapping. We use a diffusion weighted inversion recovery spin echo (DW-IR-SE) sequence with spiral readouts at ultra-strong gradients to acquire a rich diffusion-relaxation data set with sensitivity to myelin water. We reconstruct 1D and 2D spectra with a two-step convex optimization approach and investigate a variety of multidimensional MRI methods, including 1D multi-component relaxometry, 1D multi-component diffusometry, 2D relaxation correlation imaging, and 2D diffusion-relaxation correlation spectroscopic imaging (DR-CSI), in terms of their potential to quantify tissue microstructure, including the myelin water fraction (MWF). We observe a distinct spectral peak that we attribute to myelin water in multi-component T1 relaxometry, T1-T2 correlation, T1-D correlation, and T2-D correlation imaging. Due to lower achievable echo times compared to diffusometry, MWF maps from relaxometry have higher quality. Whilst 1D multi-component T1 data allows much faster myelin mapping, 2D approaches could offer unique insights into tissue microstructure and especially myelin diffusion.

Mapping the human connectome using diffusion MRI at 300 mT/m gradient strength: Methodological advances and scientific impact.

Tremendous efforts have been made in the last decade to advance cutting-edge MRI technology in pursuit of mapping structural connectivity in the living human brain with unprecedented sensitivity and speed. The first Connectom 3T MRI scanner equipped with a 300 mT/m whole-body gradient system was installed at the Massachusetts General Hospital in 2011 and was specifically constructed as part of the Human Connectome Project. Since that time, numerous technological advances have been made to enable the broader use of the Connectom high gradient system for diffusion tractography and tissue microstructure studies and leverage its unique advantages and sensitivity to resolving macroscopic and microscopic structural information in neural tissue for clinical and neuroscientific studies. The goal of this review article is to summarize the technical developments that have emerged in the last decade to support and promote large-scale and scientific studies of the human brain using the Connectom scanner. We provide a brief historical perspective on the development of Connectom gradient technology and the efforts that led to the installation of three other Connectom 3T MRI scanners worldwide - one in the United Kingdom in Cardiff, Wales, another in continental Europe in Leipzig, Germany, and the latest in Asia in Shanghai, China. We summarize the key developments in gradient hardware and image acquisition technology that have formed the backbone of Connectom-related research efforts, including the rich array of high-sensitivity receiver coils, pulse sequences, image artifact correction strategies and data preprocessing methods needed to optimize the quality of high-gradient strength diffusion MRI data for subsequent analyses. Finally, we review the scientific impact of the Connectom MRI scanner, including advances in diffusion tractography, tissue microstructural imaging, ex vivo validation, and clinical investigations that have been enabled by Connectom technology. We conclude with brief insights into the unique value of strong gradients for diffusion MRI and where the field is headed in the coming years.

MR Fingerprinting with b-Tensor Encoding for Simultaneous Quantification of Relaxation and Diffusion in a Single Scan.

PURPOSE: Although both relaxation and diffusion imaging are sensitive to tissue microstructure, studies have reported limited sensitivity and robustness of using relaxation or conventional diffusion alone to characterize tissue microstructure. Recently, it has been shown that tensor-valued diffusion encoding and joint relaxation-diffusion quantification enable more reliable quantification of compartment-specific microstructural properties. However, scan times to acquire such data can be prohibitive. Here, we aim to simultaneously quantify relaxation and diffusion using MR fingerprinting (MRF) and b-tensor encoding in a clinically feasible time. METHODS: We developed multidimensional MRF scans (mdMRF) with linear and spherical b-tensor encoding (LTE and STE) to simultaneously quantify T1, T2, and ADC maps from a single scan. The image quality, accuracy, and scan efficiency were compared between the mdMRF using LTE and STE. Moreover, we investigated the robustness of different sequence designs to signal errors and their impact on the maps. RESULTS: T1 and T2 maps derived from the mdMRF scans have consistently high image quality, while ADC maps are sensitive to different sequence designs. Notably, the fast imaging steady state precession (FISP)-based mdMRF scan with peripheral pulse gating provides the best ADC maps that are free of image distortion and shading artifacts. CONCLUSION: We demonstrated the feasibility of quantifying T1, T2, and ADC maps simultaneously from a single mdMRF scan in around 24 s/slice. The map quality and quantitative values are consistent with the reference scans.

A Phase Ib Study to Evaluate the MEK Inhibitor Cobimetinib in Combination with the ERK1/2 Inhibitor GDC-0994 in Patients with Advanced Solid Tumors.

LESSONS LEARNED: Despite strong preclinical rationale, combined cobimetinib-mediated MEK inhibition and GDC-0994-mediated ERK inhibition was not tolerable on two 28-day dosing schedules in which GDC-0994 was given for 21 days continuously and cobimetinib administered over 21 days either continuously or intermittently. Adverse events were as expected for mitogen-activated protein kinase pathway inhibition, but overlapping and cumulative toxicities could not be managed on either dosing schedule. Pharmacokinetic parameters of cobimetinib and GDC-0994 given in combination were similar to those previously observed in monotherapy studies, so that there was no evidence of drug-drug interaction. Cycle 1 metabolic responses were observed by 18F-fluorodeoxyglucose-positron emission tomography but were not predictive of outcome measured by RECIST 1.1. BACKGROUND: Simultaneous targeting of multiple nodes in the mitogen-activated protein kinase (MAPK) pathway offers the prospect of enhanced activity in RAS-RAF-mutant tumors. This phase Ib trial evaluated the combination of cobimetinib (MEK inhibitor) and GDC-0994 (ERK inhibitor) in patients with locally advanced or metastatic solid tumors. METHODS: Cobimetinib and GDC-0994 were administered orally on two separate dosing schedules. Arm A consisted of concurrent cobimetinib and GDC-0994 once daily for 21 days of a 28-day cycle; Arm B consisted of intermittent dosing of cobimetinib on a 28-day cycle concurrent with GDC-0994 daily for 21 days of a 28-day cycle. RESULTS: In total, 24 patients were enrolled. For Arm A, owing to cumulative grade 1-2 toxicity, the dose of cobimetinib was decreased. For Arm B, dose increases of GDC-0994 and cobimetinib were intolerable with grade 3 dose-limiting toxicities of myocardial infarction and rash. Pharmacokinetic data did not show evidence of a drug-drug interaction. Overall, seven patients had a best overall response of stable disease (SD) and one patient with pancreatic adenocarcinoma had an unconfirmed partial response. CONCLUSION: The safety profile of MEK and ERK inhibition demonstrated classic MAPK inhibitor-related adverse events (AEs). However, overlapping AEs and cumulative toxicity could not be adequately managed on either dosing schedule, restricting the ability to further develop this combination.

Eddy current compensated double diffusion encoded (DDE) MRI.

PURPOSE: Eddy currents might lead to image distortions in diffusion-weighted echo planar imaging. A method is proposed to reduce their effects on double diffusion encoding (DDE) MRI experiments and the thereby derived microscopic fractional anisotropy (µFA). METHODS: The twice-refocused spin echo scheme was adapted for DDE measurements. To assess the effect of individual diffusion encodings on the image distortions, measurements of a grid of plastic rods in water were performed. The effect of eddy current compensation on µFA measurements was evaluated in the brains of six healthy volunteers. RESULTS: The use of an eddy current compensation reduced the signal variation. As expected, the distortions caused by the second encoding were larger than those of the first encoding, entailing a stronger need to compensate for them. For an optimal result, however, both encodings had to be compensated. The artifact reduction strongly improved the measurement of the µFA in ventricles and gray matter by reducing the overestimation. An effect of the compensation on absolute µFA values in white matter was not observed. CONCLUSION: It is advisable to compensate both encodings in DDE measurements for eddy currents. Magn Reson Med 77:328-335, 2017. © 2015 Wiley Periodicals, Inc.

Limits of and Complications after Embolization of the Hepatic Artery and Portal Vein to Induce Segmental Hypertrophy of the Liver: A Large Mini-Pig Study.

BACKGROUND: The aim of this study was to compare arterial embolization (AE) with portal vein embolization (PVE) for the induction of segmental hypertrophy regarding procedural efficacy, safety and outcome. METHODS: A total of 29 mini pigs were subjected to PVE, AE or assigned to the sham (SO) group. Correspondingly, 75% of the hepatic artery or portal vein branches were embolized. Growth and atrophy of the liver lobes, calculating the liver-to-body weight index (LBWI), laboratory data, arteriography, portography, Doppler ultrasound (US) and histopathology were analyzed. RESULTS: After PVE, 2 animals had to be excluded due to technical problems. After AE, 4 animals had to be excluded because of technical problems and early sacrifice. Postprocedural US demonstrated effective AE and PVE of the respective lobes. Four weeks after PVE, portography showed a slow refilling of the embolized lobe by collateral portal venous vessels. Four weeks after AE, arteriography revealed a slight revascularization of the embolized lobes by arterial neovascularization. Segmental AE led to extensive necrotic and inflammatory alterations in the liver and bile duct parenchyma. Significant hypertrophy of the non-embolized lobe was only noted in the PVE group (LBWI: 0.91 ± 0.28%; p = 0.001). There was no increase in the non-embolized lobe in the AE (LBWI: 0.45 ± 0.087%) and SO group (LBWI: 0.45 ± 0.13%). CONCLUSION: PVE is safe and effective to induce segmental hypertrophy. Portal reperfusion by collateral vessels may limit hypertrophy. AE did not increase the segmental hepatic volume but carries the risk of extensive necrotic inflammatory damage.

Interplay between endothelin and erythropoietin in astroglia: the role in protection against hypoxia.

We show that, under in vitro conditions, the vulnerability of astroglia to hypoxia is reflected by alterations in endothelin (ET)-1 release and capacity of erythropoietin (EPO) to regulate ET-1 levels. Exposure of cells to 24 h hypoxia did not induce changes in ET-1 release, while 48-72 h hypoxia resulted in increase of ET-1 release from astrocytes that could be abolished by EPO. The endothelin receptor type A (ETA) antagonist BQ123 increased extracellular levels of ET-1 in human fetal astroglial cell line (SV-FHAS). The survival and proliferation of rat primary astrocytes, neural precursors, and neurons upon hypoxic conditions were increased upon administration of BQ123. Hypoxic injury and aging affected the interaction between the EPO and ET systems. Under hypoxia EPO decreased ET-1 release from astrocytes, while ETA receptor blockade enhanced the expression of EPO mRNA and EPO receptor in culture-aged rat astroglia. The blockade of ETA receptor can increase the availability of ET-1 to the ETB receptor and can potentiate the neuroprotective effects of EPO. Thus, the new therapeutic use of combined administration of EPO and ETA receptor antagonists during hypoxia-associated neurodegenerative disorders of the central nervous system (CNS) can be suggested.

Smartphone Bolus Feature Increases Number of Insulin Boluses in People With Low Bolus Frequency.

BACKGROUND: The t:connect mobile app from Tandem Diabetes Care recently added a feature to allow t:slim X2 insulin pump users to initiate an insulin bolus from their personal smartphone. User experience and user interface considerations prioritized safety and ease of use, and we examined whether the smartphone bolus feature changed bolus behavior in individuals who bolused less than three times/day. METHODS: We performed a retrospective analysis of t:slim X2 insulin pump users in the United States who had remotely updated their insulin pump software to be compatible with the smartphone bolus version of the app and who gave less than three boluses per day prior to the smartphone bolus update. RESULTS: Of the 4470 early adopters who met these criteria, the median number of boluses was 2.2 per day (prior to smartphone bolus update) versus 2.7 per day (after smartphone bolus update), equating to approximately half a bolus more delivered per day (P < .001). Overall, a median of one bolus per day was administered by smartphone app as opposed to being initiated from the screen on the insulin pump. CONCLUSION: This analysis found a significant increase in bolusing behavior among early adopters of the smartphone bolus feature of the t:connect mobile app.

Real-World Use of Control-IQ Technology Is Associated with a Lower Rate of Severe Hypoglycemia and Diabetic Ketoacidosis Than Historical Data: Results of the Control-IQ Observational (CLIO) Prospective Study.

Objective: Severe hypoglycemia (SH) and diabetic ketoacidosis (DKA) remain significant risks with intensive insulin therapy. While these adverse event (AE) rates are generally very low in advanced hybrid closed-loop (AHCL) clinical studies, prospectively collected real-world AE rates are lacking. Research Design and Methods: The Control-IQ Observational (CLIO) study was a single-arm, prospective, longitudinal, postmarket surveillance study of individuals with type 1 diabetes (T1D) age 6 years and older who began the use of t:slim X2 insulin pump with Control-IQ technology in the real-world outpatient setting. AEs were reported monthly over 12 months and were compared to historical data from the T1D Exchange. Patient-reported outcomes were assessed quarterly. All study visits were virtual. Results: Three thousand one hundred fifty-seven participants enrolled from August 2020 through March 2022. Two thousand nine hundred ninety-eight participants completed through 12 months. SH rates were significantly lower than historic rates for children (9.31 vs. 19.31 events/100 patient years, d = 0.29, P < 0.01) and adults (9.77 vs. 29.49 events/100 patient years, d = 0.53, P < 0.01). DKA rates were also significantly lower in both groups. Lower observed rates of AEs occurred independent of baseline hemoglobin A1c or prior insulin delivery method. Time in range 70-180 mg/dL was 70.1% (61.0-78.8) for adults, 61.2% (52.4-70.5) for age 6-13, 60.9% (50.1-71.8) for age 14-17, and 67.3% (57.4-76.9) overall. Reduction in diabetes burden was consistently reported. Conclusions: SH and DKA rates were lower for users of t:slim X2 with Control-IQ technology compared to historical data for both adults and children. Real-world use of this AHCL system proved safe and effective in this virtual study design. The study was registered at clinicaltrials.gov (NCT04503174).

Safety and Feasibility Evaluation of Automated User Profile Settings Initialization and Adaptation With Control-IQ Technology.

BACKGROUND: Optimization of automated insulin delivery (AID) settings is required to achieve desirable glycemic outcomes. We evaluated safety and efficacy of a computerized system to initialize and adjust insulin delivery settings for the t:slim X2 insulin pump with Control-IQ technology in adults with type 1 diabetes (T1D). METHODS: After a 2-week continuous glucose monitoring (CGM) run-in period, adults with T1D using multiple daily injections (MDI) (N = 33, mean age 36.1 years, 57.6% female, diabetes duration 19.7 years) were transitioned to 13 weeks of Control-IQ technology usage. A computerized algorithm generated recommendations for initial pump settings (basal rate, insulin-to-carbohydrate ratio, and correction factor) and weekly follow-up settings to optimize glycemic outcomes. Physicians could override the automated settings changes for safety concerns. RESULTS: Time in range 70 to 180 mg/dL improved from 45.7% during run-in to 69.1% during the last 30 days of Control-IQ use, a median improvement of 18.8% (95% confidence interval [CI]: 13.6-23.9, P < .001). This improvement was evident early in the study and was sustained over 13 weeks. Time <70 mg/dL showed a gradual decreasing trend over time. Percentage of participants achieving HbA1c <7% went from zero at baseline to 55% at study end (P < .001). Only six of the 318 automated settings adaptations (1.9%) were overridden by study investigators. CONCLUSIONS: Computerized initiation and adaptation of Control-IQ technology settings from baseline MDI therapy was safe in adults with T1D. The use of this simplified system for onboarding and optimizing Control-IQ technology may be useful to increase uptake of AID and reduce staff and patient burden in clinical care.

Locking-plate osteosynthesis versus intramedullary nailing for fixation of olecranon fractures: a biomechanical study.

PURPOSE: Intramedullary nailing and locked plating for fixation of olecranon fractures has recently gained popularity. However, these two new technologies have not been compared for their biomechanical efficacy. The aim of this study was to evaluate the biomechanical stability of two newly designed fracture fixation devices for treating olecranon fractures during dynamic continuous loading: the ION intramedullary locking nail and the LCP precontoured locking compression plate. METHODS: Simulated oblique olecranon fractures were created in eight pairs of fresh-frozen cadaver ulnae and stabilised using either the LCP or ION. Specimens were then subjected to continuous dynamic loading (from 25 to 200 N), with a continuous angle alteration between 0° and 90° of flexion, to perform a matched-pairs comparison. Significant differences in the distance between markers surrounding the fracture gap was determined using the Wilcoxon test after four and 300 loading cycles. RESULTS: The ION resulted in significantly less displacement in the fracture gap at 0° extension (P = 0.036), 45° flexion (P = 0.035) and 90° flexion (P = 0.017) after 300 cycles of continuous loading. The measured displacements were small and were probably not of clinical significance. No mechanical failure or hardware migration was seen with either fixation technique. CONCLUSION: This study shows significantly less micromotion for the ION than for the LCP in treating oblique olecranon fractures after 300 cycles of dynamic loading. Both implant types could be appropriate surgical techniques for fixation of selected olecranon fractures and osteotomies.

Practical considerations of diffusion-weighted MRS with ultra-strong diffusion gradients.

Introduction: Diffusion-weighted magnetic resonance spectroscopy (DW-MRS) offers improved cellular specificity to microstructure-compared to water-based methods alone-but spatial resolution and SNR is severely reduced and slow-diffusing metabolites necessitate higher b-values to accurately characterize their diffusion properties. Ultra-strong gradients allow access to higher b-values per-unit time, higher SNR for a given b-value, and shorter diffusion times, but introduce additional challenges such as eddy-current artefacts, gradient non-uniformity, and mechanical vibrations. Methods: In this work, we present initial DW-MRS data acquired on a 3T Siemens Connectom scanner equipped with ultra-strong (300 mT/m) gradients. We explore the practical issues associated with this manner of acquisition, the steps that may be taken to mitigate their impact on the data, and the potential benefits of ultra-strong gradients for DW-MRS. An in-house DW-PRESS sequence and data processing pipeline were developed to mitigate the impact of these confounds. The interaction of TE, b-value, and maximum gradient amplitude was investigated using simulations and pilot data, whereby maximum gradient amplitude was restricted. Furthermore, two DW-MRS voxels in grey and white matter were acquired using ultra-strong gradients and high b-values. Results: Simulations suggest T2-based SNR gains that are experimentally confirmed. Ultra-strong gradient acquisitions exhibit similar artefact profiles to those of lower gradient amplitude, suggesting adequate performance of artefact mitigation strategies. Gradient field non-uniformity influenced ADC estimates by up to 4% when left uncorrected. ADC and Kurtosis estimates for tNAA, tCho, and tCr align with previously published literature. Discussion: In conclusion, we successfully implemented acquisition and data processing strategies for ultra-strong gradient DW-MRS and results indicate that confounding effects of the strong gradient system can be ameliorated, while achieving shorter diffusion times and improved metabolite SNR.

The anatomy of the proximal radius: implications on fracture implant design.

BACKGROUND: The proximal radius features a complex anatomy. Several studies have been published on the anatomy using different technical approaches; however, most of these studies were conducted with a special focus on parameters relevant to radial prosthetic design. The purpose of our study was to explore the complex geometry of the proximal radius with regard to fracture implant design. METHODS: Our computed tomography-based measurements of 78 multiplanar reformatted radii allow for exact assessment of its geometry and offer a scientific rationale towards the design of fracture implants. We conducted measurements on the radial head, the radial neck, the radial tuberosity, the radial head-to-neck angle, and the safe zone. RESULTS: A wide range of normal anatomy has been demonstrated for all parameters. Sex differences are statistically significant in all registered parameters, except the radial head-to-neck angle. Although measurements of maximum vs minimum radial head, neck, and tuberosity diameters show close correlation, diameter-to-length correlations, such as radial head diameter vs radial head height and radial neck diameter vs radial neck length, are low. CONCLUSIONS: Besides the wide range in size, intraindividual parameter variations have to be taken into account in the design of anatomically precontoured plates. The results of this study indicate that these plates will still need to offer the ability of "bend to match."

Biobehavioral Changes Following Transition to Automated Insulin Delivery: A Large Real-life Database Analysis.

OBJECTIVE: To document glycemic and user-initiated bolus changes following transition from predictive low glucose suspend (PLGS) system to automated insulin delivery (AID) system during real-life use. RESEARCH DESIGN AND METHODS: We conducted analysis of 2,329,166 days (6,381 patient-years) of continuous glucose monitoring (CGM) and insulin therapy data for 19,354 individuals with type 1 Diabetes, during 1-month PLGS use (Basal-IQ technology) followed by 3-month AID use (Control-IQ technology). Baseline characteristics are as follows: 55.4% female, age (median/quartiles/range) 39/19-58/1-92 years, mean ± SD glucose management indicator (GMI) 7.5 ± 0.8. Primary outcome was time in target range (TIR) (70-180 mg/dL). Secondary outcomes included CGM-based glycemic control metrics and frequency of user-initiated boluses. RESULTS: Compared with PLGS, AID increased TIR on average from 58.4 to 70.5%. GMI and percent time above and below target range improved as well: from 7.5 to 7.1, 39.9 to 28.1%, and 1.66 to 1.46%, respectively; all P values <0.0001. Stratification of outcomes by age and baseline GMI revealed clinically significant differences. Glycemic improvements were most pronounced in those <18 years old (TIR improvement 14.0 percentage points) and those with baseline GMI >8.0 (TIR improvement 13.2 percentage points). User-initiated correction boluses decreased from 2.7 to 1.8 per day, while user-initiated meal boluses remained stable at 3.6 to 3.8 per day. CONCLUSIONS: Observed in real life of >19,000 individuals with type 1 diabetes, transitions from PLGS to AID resulted in improvement of all glycemic parameters, equivalent to improvements observed in randomized clinical trials, and reduced user-initiated boluses. However, glycemic and behavioral changes with AID use may differ greatly across different demographic and clinical groups.

Antioxidant activity of ß-carotene compounds in different in vitro assays.

ß-Carotene (BC) is the most abundant carotenoid in human diet, almost solely as(all-E)-isomer. Significant amounts of (Z)-isomers of BC are present in processed food as well as in mammalian tissues. Differences are described for the activity of various BC isomers in forming retinal and protecting against cancer and cardiovascular diseases. Eccentric cleavage of BC leads to degradation products such as carotenals. A variety of negative consequences were published for the non-vitamin A active BC metabolites, such as inducing the carcinogenesis of benzo[a]pyrene, impairing mitochondrial function, or increasing CYP activity. To increase the knowledge on the antioxidant activity, a variety of BC isomers and metabolites were tested in various in vitro assays. In the present study, no ferric reducing activity (FRAP assay) was observed for the BC isomers. Between the major BC isomers (all-E, 9Z, and 13Z) no significant differences in bleaching the ABTS●+ (αTEAC assay) or in scavenging peroxyl radicals (ROO●) generated by thermal degradation of AAPH (using a chemiluminescence assay) were detected.However, the (15Z)-isomer was less active, maybe due to its low stability. The degradation to ß-apo-carotenoids increased FRAP activity and ROO● scavenging activity compared to the parent molecule. Dependence on chain length and character of the terminal function was determined in αTEAC assay with following order of increasing activity: ß-apo-8'-carotenal < ß-apo-8'-carotenoic acid ethyl ester < 6'-methyl-ß-apo-6'-carotene-6'-one (citranaxanthin). The results indicate that BC does not lose its antioxidant activity by degradation to long chain breakdown products.

TNF-alpha similarly induces IL-6 and MCP-1 in fibroblasts from colorectal liver metastases and normal liver fibroblasts.

Cancer-associated fibroblasts (CAFs) represent the predominant cell type of the neoplastic stroma of solid tumors, yet their biology and functional specificity for cancer pathogenesis remain unclear. We show here that primary CAFs from colorectal liver metastases express several inflammatory, tumor-enhancing factors, including interleukin (IL)-6 and monocyte-chemoattractant protein (MCP)-1. Both molecules were intensely induced by TNF-alpha on the transcript and protein level, whereas PDGF-BB, TGF-beta1 and EGF showed no significant effects. To verify their potential specialization for metastasis progression, CAFs were compared to fibroblasts from non-tumor liver tissue. Interestingly, these liver fibroblasts (LFs) displayed similar functions. Further analyses revealed a comparable up-regulation of intercellular adhesion molecule-1 (ICAM-1) by TNF-alpha, and of alpha-smooth muscle actin, by TGF-beta1. Moreover, the proliferation of both cell types was induced by PDGF-BB, and CAFs and LFs displayed an equivalent migration towards HT29 colon cancer cells in Boyden chamber assays. In conclusion, colorectal liver metastasis may be supported by CAFs and resident fibroblastic cells competent to generate a prometastatic microenvironment through inflammatory activation of IL-6 and MCP-1.

New intramedullary locking nail for olecranon fracture fixation--an in vitro biomechanical comparison with tension band wiring.

BACKGROUND: The aim of this study was to determine the difference in displacement of a newly designed intramedullary olecranon fracture fixation device compared with multifilament tension band wiring after 4 cycles and 300 cycles of dynamic continuous loading. METHODS: In eight pairs of fresh-frozen cadaver ulnae, oblique olecranon fractures were created and stabilized using either newly designed intramedullary olecranon nail or multifilament tension band wiring. The specimens were then subjected to continuous dynamic loading (from 25 N to 200 N) using matched pairs of cadaveric upper extremities. The Wilcoxon test was used to determine statistical differences of the displacement in the fracture gap. RESULTS: After 4 cycles and 300 cycles, the displacement in the fracture model was significantly higher in the tension band wiring group than in the intramedullary nailing group. CONCLUSIONS: The newly designed interlocking nailing system showed higher stability in comparison with multifilament tension band wiring after continuous dynamic loading.