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IntroductionA main obstacle that impedes standardized clinical and research applications of arterial spin labeling (ASL), is the substantial differences between the commercial implementations of ASL from major MRI vendors. In this study, we compare a single identical 2D gradient-echo EPI pseudo-continuous ASL (PCASL) sequence implemented on 3T scanners from three vendors (General Electric Healthcare, Philips Healthcare and Siemens Healthcare) within the same center and with the same subjects.Material and methodsFourteen healthy volunteers (50% male, age 26.4±4.7years) were scanned twice on each scanner in an interleaved manner within 3h. Because of differences in gradient and coil specifications, two separate studies were performed with slightly different sequence parameters, with one scanner used across both studies for comparison. Reproducibility was evaluated by means of quantitative cerebral blood flow (CBF) agreement and inter-session variation, both on a region-of-interest (ROI) and voxel level. In addition, a qualitative similarity comparison of the CBF maps was performed by three experienced neuro-radiologists.ResultsThere were no CBF differences between vendors in study 1 (p>0.1), but there were CBF differences of 2-19% between vendors in study 2 (p0.1) but one of the ROIs (p

QUASAR arterial spin labeling (ASL) was used to investigate the role of vascular impairment in Alzheimer's disease (AD). We hypothesized that the hemodynamic parameters monitoring cerebrovascular integrity, i.e., cerebral blood flow (CBF), arterial blood volume (aBV), and arterial transit time (aTT), would be affected. 13 AD patients and 15 healthy control (HC) subjects underwent 3T MRI scanning. Two separate blood flow acquisitions were obtained with 1 slice overlap for whole brain coverage. CBF, aBV, and aTT maps were calculated using in-house software. Preprocessing and statistical analyses were performed on SPM5. Region-of-interest (ROI) studies of ten selected cerebral regions were also conducted. There were significant differences in mini mental status exam (MMSE) (AD: 16.3 ± 4.55, HC: 28.5 ± 2.00) and Alzheimer's disease assessment scale-cognitive subscale (ADAS-cog) scores (AD: 25.25 ± 9.64, HC: 5.51 ± 2.62) between the 2 groups (p < 0.001) but none in age (p = 0.068). CBF decreased significantly (p < 0.01) in AD compared to controls in the right middle cingulate, left cuneus, left inferior and middle frontal, right superior frontal, left inferior parietal, and right supramarginal gyri. ROI studies confirmed significant hemodynamic impairments in AD compared to HC (p < 0.05): CBF in middle and posterior cingulate, aBV in left superior temporal, right inferior parietal, and posterior cingulate, and aTT in left inferior frontal and middle cingulate gyri. CBF correlated positively while aTT correlated negatively to MMSE, and vice versa for ADAS-cog. Using QUASAR ASL, we found patterns of regional hemodynamic impairment typical of moderate AD, suggesting underlying vascular abnormality. As potential biomarkers, these hemodynamic parameters could differentiate patients from volunteers, and possibly indicate the conversion from healthy aging to mild cognitive impairment to AD. [ABSTRACT FROM AUTHOR]

Aims: The aim of this study was to evaluate the kinematics of the elbow following increasing length of the radius with implantation of radial head arthroplasties (RHAs) using dynamic radiostereometry (dRSA)., Methods: Eight human donor arms were examined by dRSA during motor-controlled flexion and extension of the elbow with the forearm in an unloaded neutral position, and in pronation and supination with and without a 10 N valgus or varus load, respectively. The elbows were examined before and after RHA with stem lengths of anatomical size, + 2 mm, and + 4 mm. The ligaments were maintained intact by using a step-cut lateral humeral epicondylar osteotomy, allowing the RHAs to be repeatedly exchanged. Bone models were obtained from CT scans, and specialized software was used to match these models with the dRSA recordings. The flexion kinematics of the elbow were described using anatomical coordinate systems to define translations and rotations with six degrees of freedom., Results: The greatest kinematic changes in the elbows were seen with the longest, + 4 mm, implant, which imposed a mean joint distraction of 2.8 mm in the radiohumeral joint and of 1.1 mm in the ulnohumeral joint, an increased mean varus angle of up to 2.4° for both the radius and the ulna, a mean shift of the radius of 2.0 mm in the ulnar direction, and a mean shift of the ulna of 1.0 mm posteriorly., Conclusion: The kinematics of the elbow deviated increasingly from those of the native joint with a 2 mm to a 4 mm lengthening of the radius. This confirms the importance of restoring the natural length of the radius when undertaking RHA., Competing Interests: J. Frost Teilmann and T. M. Thillemann report material support from Acumed, which provided the implants (radial head arthroplasties) for the study but had no influence on the conduction of the study or the interpretation of the results/publication. J. Frost Teilmann also reports funding from Ortopædkirurgisk Forskningsfond, related to this study, and a research grant from the P. Carl Petersens Fund, unrelated to this study. T. M. Thillemann reports funding from the A. P. Møller Fund (Fonden til lægevidenskabens fremme) and the Familien Hede Nielsen Fund, related to this study. M. Stilling reports a grant from the P. Carl Petersens Fund, unrelated to this study., (© 2024 The British Editorial Society of Bone & Joint Surgery.)

Aims: This study aimed to quantify the shoulder kinematics during an apprehension-relocation test in patients with anterior shoulder instability (ASI) and glenoid bone loss using the radiostereometric analysis (RSA) method. Kinematics were compared with the patient's contralateral healthy shoulder., Methods: A total of 20 patients with ASI and > 10% glenoid bone loss and a healthy contralateral shoulder were included. RSA imaging of the patient's shoulders was performed during a repeated apprehension-relocation test. Bone volume models were generated from CT scans, marked with anatomical coordinate systems, and aligned with the digitally reconstructed bone projections on the RSA images. The glenohumeral joint (GHJ) kinematics were evaluated in the anteroposterior and superoinferior direction of: the humeral head centre location relative to the glenoid centre; and the humeral head contact point location on the glenoid., Results: During the apprehension test, the centre of the humeral head was 1.0 mm (95% CI 0.0 to 2.0) more inferior on the glenoid for the ASI shoulder compared with the healthy shoulder. Furthermore, the contact point of the ASI shoulder was 1.4 mm (95% CI 0.3 to 2.5) more anterior and 2.0 mm (95% CI 0.8 to 3.1) more inferior on the glenoid compared with the healthy shoulder. The contact point of the ASI shoulder was 1.2 mm (95% CI 0.2 to 2.6) more anterior during the apprehension test compared to the relocation test., Conclusion: The humeral head centre was located more inferior, and the GHJ contact point was located both more anterior and inferior during the apprehension test for the ASI shoulders than the healthy shoulders. Furthermore, the contact point displacement between the apprehension and relocation test revealed increased joint laxity for the ASI shoulder than the healthy shoulders. These results contribute to existing knowledge that ASI shoulders with glenoid bone loss may also suffer from inferior shoulder instability., Competing Interests: J. Olsen Kipp reports funding from the Health Research Foundation of Central Denmark Region and Torben og Alice Frimodts Fond, related to this study. M. Stilling reports funding from the Inge og Asker Larsens Fond, Grosser L F Foghts Familien Hede Nielsen, and Danish Rheumatism Association, related to this study. J. Olsen Kipp, E. T. Petersen, J. Frost Teilmann, S. de Raedt, and M. Stilling are affiliated with the AutoRSA Research Group., (© 2024 The British Editorial Society of Bone & Joint Surgery.)

Purpose: Radial head arthroplasty (RHA) reestablishes elbow stability after complex radial head fracture, but complication rates are high, possibly due to inappropriate implant sizing. Knowledge of impact of radial head implant diameter on elbow kinematics is limited and warranted. This study evaluated elbow kinematics of different radial head implant diameters after RHA using dynamic radiostereometric analysis (dRSA)., Methods: Eight human donor arms were examined with dRSA during elbow flexion with the forearm in unloaded neutral position, and in supinated- and pronated position without and with 10N either varus or valgus load, respectively. Elbow kinematics were examined before and after RHA with head diameters of anatomical size, -2 mm (undersized), and +2 mm (oversized). The ligaments were kept intact by use of step-cut humerus osteotomy for repeated RHA exchange. Bone models were obtained from CT, and by AutoRSA software bone models were matched with dRSA recordings. The elbow kinematics were described using anatomical coordinate systems., Results: Compared to the native radial head during elbow flexion, the anatomical sized RHA shifted 2.0 mm in ulnar direction during unloaded pronated forearm position. The undersized RHA shifted 1.5 mm in posterior direction and 2.1 mm in ulnar direction during unloaded pronated forearm position and increased the varus angle by 2.4° during supinated loaded forearm position. The oversized RHA shifted 1.6 mm in radial direction during loaded supinated forearm position., Conclusions: The anatomically sized RHA should be preferred as it maintained native elbow kinematics the best. The kinematic changes with oversized and undersized RHA diameters were small, suggesting forgiveness for the RHA diameter size., Level of Evidence: Level III., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). Journal of Experimental Orthopaedics published by John Wiley & Sons Ltd on behalf of European Society of Sports Traumatology, Knee Surgery and Arthroscopy.)

Purpose: The pivot-shift test is used to clinically assess knee instability in patients with anterior cruciate ligament (ACL) lesions; however, it has low interobserver reliability. Dynamic radiostereometry (dRSA) is a highly precise and noninvasive method for the objective evaluation of joint kinematics. The purpose of this study was to quantify precise knee kinematics during a pivot-shift test using dRSA imaging., Method: Eight human donor legs, including hemipelvises, were evaluated. Arthroscopic intervention was performed inducing ligament lesions in the ACL, and anterolateral ligament (ALL) section was performed as a capsular incision. The pivot-shift test was recorded with dRSA on knees with intact ligaments, ACL-deficient and ACL + ALL-deficient knees., Results: A pivot-shift pattern was identifiable after ligament lesion, as a change in tibial posterior drawer velocity from 7.8 mm/s (95% CI: 3.7; 11.9) in ligament intact knees to 30.4 mm/s (95% CI 23.0; 38.8) after ACL lesion to 35.1 mm/s (95% CI 23.4; 46.7) after combined ACL-ALL lesion. The anterior-posterior drawer excursion increased from 2.8 mm (95% CI 2.1; 3.4) in ligament intact knees to 7.2 mm (95% CI 5.5; 8.9) after ACL lesion to 7.6 mm (95% CI 5.5; 9.8) after combined lesion. A statistically significant increase in tibial external rotation towards the end of the pivot-shift motion was observed when progressing from intact to ACL + ALL-deficient knees (p < 0.023)., Conclusion: This experimental study demonstrates the feasibility of dRSA to objectively quantify the kinematic laxity patterns of the knee during the pivot-shift test. The dynamic parameters obtained through dRSA revealed the kinematic changes from ACL to combined ACL-ALL ligament lesion., Level of Evidence: Not applicable., (© 2024 The Authors. Knee Surgery, Sports Traumatology, Arthroscopy published by John Wiley & Sons Ltd on behalf of European Society of Sports Traumatology, Knee Surgery and Arthroscopy.)

Aims: Micromotion of the polyethylene (PE) inlay may contribute to backside PE wear in addition to articulate wear of total knee arthroplasty (TKA). Using radiostereometric analysis (RSA) with tantalum beads in the PE inlay, we evaluated PE micromotion and its relationship to PE wear., Methods: A total of 23 patients with a mean age of 83 years (77 to 91), were available from a RSA study on cemented TKA with Maxim tibial components (Zimmer Biomet). PE inlay migration, PE wear, tibial component migration, and the anatomical knee axis were evaluated on weightbearing stereoradiographs. PE inlay wear was measured as the deepest penetration of the femoral component into the PE inlay., Results: At mean six years' follow-up, the PE wear rate was 0.08 mm/year (95% confidence interval 0.06 to 0.09 mm/year). PE inlay external rotation was below the precision limit and did not influence PE wear. Varus knee alignment did not influence PE wear (p = 0.874), but increased tibial component total translation (p = 0.041)., Conclusion: The PE inlay was well fixed and there was no relationship between PE stability and PE wear. The PE wear rate was low and similar in the medial and lateral compartments. Varus knee alignment did not influence PE wear., Competing Interests: The authors report funding for this study from the A. P. Møller Foundation, Zimmer Biomet, and the Danish Rheumatism Association. M. Stilling is also the unpaid President of the International RSA Society., (© 2024 Jürgens-Lahnstein et al.)

Background and Objectives: Reliable detection of white matter hyperintensities (WMH) is crucial for studying the impact of diffuse white-matter pathology on brain health and monitoring changes in WMH load over time. However, manual annotation of 3D high-dimensional neuroimages is laborious and can be prone to biases and errors in the annotation procedure. In this study, we evaluate the performance of deep learning (DL) segmentation tools and propose a novel volumetric segmentation model incorporating self-attention via a transformer-based architecture. Ultimately, we aim to evaluate diverse factors that influence WMH segmentation, aiming for a comprehensive analysis of the state-of-the-art algorithms in a broader context., Methods: We trained state-of-the-art DL algorithms, and incorporated advanced attention mechanisms, using structural fluid-attenuated inversion recovery (FLAIR) image acquisitions. The anatomical MRI data utilized for model training was obtained from healthy individuals aged 62-70 years in the Live active Successful Aging (LISA) project. Given the potential sparsity of lesion volume among healthy aging individuals, we explored the impact of incorporating a weighted loss function and ensemble models. To assess the generalizability of the studied DL models, we applied the trained algorithm to an independent subset of data sourced from the MICCAI WMH challenge (MWSC). Notably, this subset had vastly different acquisition parameters compared to the LISA dataset used for training., Results: Consistently, DL approaches exhibited commendable segmentation performance, achieving the level of inter-rater agreement comparable to expert performance, ensuring superior quality segmentation outcomes. On the out of sample dataset, the ensemble models exhibited the most outstanding performance., Conclusions: DL methods generally surpassed conventional approaches in our study. While all DL methods performed comparably, incorporating attention mechanisms could prove advantageous in future applications with a wider availability of training data. As expected, our experiments indicate that the use of ensemble-based models enables the superior generalization in out-of-distribution settings. We believe that introducing DL methods in the WHM annotation workflow in heathy aging cohorts is promising, not only for reducing the annotation time required, but also for eventually improving accuracy and robustness via incorporating the automatic segmentations in the evaluation procedure., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Hartwig Roman Siebner has received honoraria as speaker from Sanofi Genzyme, Denmark, Lundbeck AS, Denmark, and Novartis, Denmark, as consultant from Sanofi Genzyme, Denmark, Lophora, Denmark, and Lundbeck AS, Denmark, and as editor-in-chief (Neuroimage Clinical) and senior editor (NeuroImage) from Elsevier Publishers, Amsterdam, The Netherlands. He has received royalties as book editor from Springer Publishers, Stuttgart, Germany, and from Gyldendal Publishers, Copenhagen, Denmark. The remaining authors declare that they have no known conflicts of interest., (Copyright © 2024. Published by Elsevier B.V.)

Background & Aims: In recent years, epidemiological studies have reported links between the consumption of fermented dairy products, such as yogurt, and health; however, evidence from human intervention trials is scarce and inconsistent. We aimed to investigate the effect of consumption of four different types of dairy products (two fermented and two non-fermented) on liver fat (primary outcome) and metabolic risk markers in males with abdominal obesity., Methods: In this parallel randomized controlled trial with four arms, 100 males aged 30-70 years, with body mass index 28.0-45.0 kg/m 2 , and waist circumference ≥102 cm underwent a 16-weeks intervention where they were instructed to consume 400 g/day of either milk, yogurt, heat-treated yogurt, or acidified milk as part of their habitual diet. Liver fat was measured by magnetic resonance imaging., Results: In the complete case analyses (n = 80), no effects of the intervention or differences between groups were detected in anthropometry or body composition including liver fat. Moreover, no effects were detected in inflammatory markers. Main effects of time were detected in blood pressure (decrease; P < 0.001), insulin (decrease; P < 0.001), C-peptide (decrease; P = 0.040), homeostatic model assessment for insulin resistance (decrease; P < 0.001), total cholesterol (decrease; P = 0.016), low-density lipoprotein (decrease; P = 0.033), high-density lipoprotein (decrease; P = 0.006), and alanine transaminase (decrease; P = 0.019). Interactions between group and time failed to reach significance., Conclusions: In conclusion, findings from our study do not confirm that fermented yogurt products are superior in reducing liver fat or improving metabolic risk markers compared to non-fermented milk products. In fact, all intervention products (both fermented yogurt products and non-fermented milk products) did not affect liver fat and caused largely similar modest favorable changes in some metabolic risk markers. The study was registered at www., Clinicaltrials: gov (# NCT04755530)., Competing Interests: Conflict of interest FM has received grants from Arla Foods A/S. TK has received grants from Arla Foods amba and Danish Dairy Research Foundation. HCB has received grants from Danish Dairy Research Foundation. NG has received grants from the Danish Agricultural and Food Council. All other authors report no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Creatine transporter deficiency (CTD), caused by pathogenic variants in SLC6A8, is the second most common cause of X-linked intellectual disability. Symptoms include intellectual disability, epilepsy, and behavioral disorders and are caused by reduced cerebral creatine levels. Targeted treatment with oral supplementation is available, however the treatment efficacy is still being investigated. There are clinical and theoretical indications that heterozygous females with CTD respond better to supplementation treatment than hemizygous males. Unfortunately, heterozygous females with CTD often have more subtle and uncharacteristic clinical and biochemical phenotypes, rendering diagnosis more difficult. We report a new female case who presented with learning disabilities and seizures. After determining the diagnosis with molecular genetic testing confirmed by proton magnetic resonance spectroscopy ( 1 H-MRS), the patient was treated with supplementation treatment including creatine, arginine, and glycine. After 28 months of treatment, the patient showed prominent clinical improvement and increased creatine levels in the brain. Furthermore, we provide a review of the 32 female cases reported in the current literature including a description of phenotypes, genotypes, diagnostic approaches, and effects of supplementation treatment. Based on this, we find that supplementation treatment should be tested in heterozygous female patients with CTD, and a prospective treatment underlines the importance of diagnosing these patients. The diagnosis should be suspected in a broad clinical spectrum of female patients and can only be made by molecular genetic testing. 1 H-MRS of cerebral creatine levels is essential for establishing the diagnosis in females, and especially valuable when assessing variants of unknown significance., Competing Interests: Declaration of Competing Interest Hartwig R. Siebner has received honoraria as speaker from Sanofi Genzyme, Denmark, Lundbeck A/S, Denmark, and Novartis, Denmark, as consultant from Sanofi Genzyme, Denmark, Lophora, Denmark, and Lundbeck A/S, Denmark, and as editor-in-chief (Neuroimage Clinical) and senior editor (NeuroImage) from Elsevier Publishers, Amsterdam, The Netherlands. He has received royalties as book editor from Springer Publishers, Stuttgart, Germany and from Gyldendal Publishers, Copenhagen, Denmark., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: New total knee arthroplasty implant designs attempt to normalize kinematics patterns that may improve functional performance and patient satisfaction. It was hypothesized that a more medial congruent (MC) anatomic bearing design (1) influences the tibiofemoral kinematics and (2) enhances articular congruency compared to a standard symmetrical cruciate retaining (CR) bearing design., Methods: In this double-blinded randomized study, 66 patients with knee osteoarthritis were randomly included in two groups: MC (n = 31) and CR (n = 33). Clinical characteristics such as knee ligament lesions and knee osteoarthritis scores were graded on preoperative magnetic resonance imaging and radiography. At the 1-year follow-up, dynamic radiostereometric analysis was used to assess tibiofemoral joint kinematics and articulation congruency. Patient-reported outcome measures, Oxford Knee Score, the Forgotten Joint Score, and the Knee Osteoarthritis Outcome Score, were assessed preoperatively and at the 1-year follow-up., Results: Compared to the CR bearing, the MC bearing displayed an offset with approximately 3 mm greater anterior tibial drawer (p < 0.001) during the entire motion, and up to approximately 3.5 degrees more tibial external rotation (p = 0.004) from mid-swing to the end of the gait cycle at the 1-year follow-up. Furthermore, the congruency area in the joint articulation was larger during approximately 80% of the gait cycle for the MC bearing compared to the CR. The patient-reported outcome measures improved (p < 0.001), but there were no differences between groups. In addition, there were no differences in clinical characteristics and there were no knee revisions or recognized deep infections during follow-up., Conclusion: The study demonstrates that the MC-bearing design changes tibiofemoral kinematics and increases the area of congruency towards more native knee kinematics than the CR bearing. In perspective this may contribute to a more stabilized knee motion, restoring the patient's confidence in knee function during daily activities., (© 2022. The Author(s) under exclusive licence to European Society of Sports Traumatology, Knee Surgery, Arthroscopy (ESSKA).)

Radiostereometic analysis (RSA) is an accurate method for rigid body pose (position and orientation) in three-dimensional space. Traditionally, RSA is based on insertion of periprosthetic tantalum markers and manual implant contour selection which limit clinically application. We propose an automated image registration technique utilizing digitally reconstructed radiographs (DRR) of computed tomography (CT) volumetric bone models (autorsa-bone) as a substitute for tantalum markers. Furthermore, an automated synthetic volumetric representation of total knee arthroplasty implant models (autorsa-volume) to improve previous silhouette-projection methods (autorsa-surface). As reference, we investigated the accuracy of implanted tantalum markers (marker) or a conventional manually contour-based method (mbrsa) for the femur and tibia. The data are presented as mean (standard deviation). The autorsa-bone method displayed similar accuracy of -0.013 (0.075) mm compared to the gold standard method (marker) of -0.013 (0.085). The autorsa-volume with 0.034 (0.106) mm did not markedly improve the autorsa-surface with 0.002 (0.129) mm, and none of these reached the mbrsa method of -0.009 (0.094) mm. In conclusion, marker-free RSA is feasible with similar accuracy as gold standard utilizing DRR and CT obtained volumetric bone models. Furthermore, utilizing synthetic generated volumetric implant models could not improve the silhouette-based method. However, with a slight loss of accuracy the autorsa methods provide a feasible automated alternative to the semi-automated method., (© 2022 The Authors. Journal of Orthopaedic Research® published by Wiley Periodicals LLC on behalf of Orthopaedic Research Society.)

Background: Non-alcoholic fatty liver disease (NAFLD), and particularly liver fibrosis, has been suggested as a risk factor of chronic kidney disease (CKD). Given that NAFLD affects every fourth person globally, better insight is needed. Our aim was to investigate the association between hepatic fibrosis and CKD in patients with type 2 diabetes and to compare different methods for diagnosing liver fibrosis in this study population., Methods: Cross-sectional study including patients with type 2 diabetes with CKD stages 3-5 (N = 50) or without CKD (N = 50). CKD was defined as estimated glomerular filtration rate &lt;60 mL/min/1.73 m2 with or without proteinuria. Three methods were used to detect significant liver fibrosis defined as either ≥8 kilopascal measured by transient elastography (FibroScan®), fibrosis-4 (FIB-4) score ≥2.67, or NAFLD fibrosis score (NFS) &gt;0.675., Results: Significant liver fibrosis was found in 38% and 28% of the patients with and without CKD, respectively, using at least one of the three methods. Both FIB-4 score and NFS were significantly higher in patients with CKD (p &lt; 0.0009 and p &lt; 0.0001, respectively), although insignificant after adjustments for age, sex, body mass index, and duration of diabetes. In patients without CKD, a significant association between steatosis and fibrosis was observed (p = 0.0007)., Conclusion: Our data do not support any strong independent association between liver fibrosis and established CKD as assessed by FibroScan, FIB-4 score, and NFS, respectively., (© 2023 S. Karger AG, Basel.)

Background: Nonalcoholic fatty liver disease (NAFLD) is suggested as a risk factor for chronic kidney disease (CKD). The incidence of NAFLD is rising globally in parallel to the increasing incidences of obesity and type 2 diabetes. Diabetes remains the leading cause of CKD, but the co-existence of NAFLD, CKD, and type 2 diabetes is not well elucidated. Here, we evaluated the prevalence of NAFLD in patients with type 2 diabetes with and without CKD., Methods: This was a cross-sectional study including 50 patients with type 2 diabetes and CKD stages 3-5 (no dialysis), and 50 patients with type 2 diabetes without CKD. Liver fat content was estimated by proton magnetic resonance spectroscopy and magnetic resonance imaging proton density fat fraction. NAFLD was defined as liver fat fraction ≥5.6% according to guidelines., Results: Mean age was 72 ± 4.9 years in patients with CKD and 65.9 ± 7.8 years in patients without CKD (p < 0.0001). Three out of four participants were men. BMI was 28.6 ± 3.5 kg/m2 and 27 ± 4.0 kg/m2 in patients with and without CKD, respectively (p = 0.0087). NAFLD was identified in 22 (44%) patients with CKD and 19 (38%) patients without CKD (p = 0.6845). Median (IQR) liver fat fraction was 4.7% (3.0-8.5) and 4.1% (2.9-7.7) in patients with and without CKD, respectively (difference in geometric means 5.3%, 95% CI -23; 45, p = 0.7463)., Conclusion: These findings do not support any association between NAFLD and CKD (stages 3-5) in patients with type 2 diabetes., (© 2023 S. Karger AG, Basel.)

Background: Patients with unilateral hip osteoarthritis appear to have between-leg differences in leg extension power (LEP). The Nottingham Leg Extensor Power Rig provides reliable and valid results but requires sensitive equipment. It would be relevant to identify measures closely associated with this test., Objective: (i) To investigate if LEP is lower in the affected leg compared to the non-affected leg. Furthermore, to investigate the associations between LEP and the measures: (ii) Functional performance, (iii) accelerometer-based measurement of physical activity and (iv) patient-reported outcome measures (PROM)., Design: Cross-sectional study including 60 patients (30 men, 30 women) with hip osteoarthritis scheduled for hip replacement., Method: The counter movement jump and 10-m sprint tests were used to determine functional performance, accelerometer-sensors were used to determine physical activity and the Copenhagen Hip and Groin Outcome Score (HAGOS) was used to determine PROM., Results: (i) LEP in the affected leg corresponded to 79% [95% CI 74%; 85%] of the non-affected leg, (ii) LEP was positively associated with functional performance tests (β 0.63 to 0.78, p < 0.05), (iii) positively associated although non-significantly with physical activity (β 0.16 to 0.23, p > 0.05) and (iv) positively associated with the six HAGOS subscales (β 0.25 to 0.54, p < 0.05)., Conclusion: Functional performance tests may be used as feasible, inexpensive and fast ways to assess LEP in clinical settings. These results may suggest that interventions aimed at improving LEP can improve functional performance and PROM, but not physical activity. Future research is needed to confirm the causality of these cross-sectional findings., The Clinical Trial Registration Numbers: Danish Data Protection Agency (1-16-02-640-14), ClinicalTrials.gov (NTC02301182) and approved by the Danish Biomedical Research Ethics Committee (1-10-72- 343-14) prior to data collection., Competing Interests: Declaration of competing interest None declared., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Object: Improve shimming capabilities of ultra-high field systems, with addition of an accessible low-complexity B 0 shim array for head MRI at 7 T., Materials and Methods: An eight channel B 0 shim coil array was designed as a tradeoff between shimming improvement and construction complexity, to provide an easy to use shim array that can be employed with the standard 7 T head coil. The array was interfaced using an open-source eight-channel shim amplifier rack. Improvements in field homogeneity for whole-brain and slice-based shimming were compared to standard second-order shimming, and to more complex higher order dynamic shimming and shim arrays with 32 and 48 channels., Results: The eight-channel shim array provided 12% improvement in whole brain static shimming and provided 33% improvement when using slice-based shimming. With this, the eight-channel array performed similar to third-order dynamic shimming (without the need for higher order eddy current compensation). More complex shim arrays with 32 and 48 channels performed better, but require a dedicated RF coil., Discussion: The designed eight-channel shim array provides a low-complexity and low-cost approach for improving B 0 field shimming on an ultra-high field system. In both static and dynamic shimming, it provides improved B 0 homogeneity over standard shimming., (© 2022. The Author(s).)

Background: Venous blood oxygenation (Yv), which can be derived from venous blood T 2 (T 2 b), combined with oxygen-extraction fraction (OEF) and cerebral metabolic rate of oxygen, is considered indicative for tissue viability and brain functioning and frequently assessed in patients with sickle cell disease. Recently, T 2 -Prepared-Blood-Relaxation-Imaging-with-Inversion-Recovery (T 2 -TRIR) was introduced allowing for simultaneous measurements of blood T 2 and T 1 (T 1 b), potentially improving Yv estimation by overcoming the need to estimate hematocrit., Purpose: To optimize and compare T 2 -TRIR with T 2 -relaxation-under-spin-tagging (TRUST) sequence., Study Type: Prospective., Population: A total of 12 healthy volunteers (six female, 27 ± 3 years old) and 7 patients with sickle cell disease (five female, 32 ± 12 years old)., Field Strength/sequence: 3 T; turbo field echo planar imaging (TFEPI), echo planar imaging (EPI), and fast field echo (FFE)., Assessment: T 2 b, Yv, and OEF from TRUST and T 2 -TRIR were compared and T 2 -TRIR-derived T 1 b was assessed. Within- and between-session repeatability was quantified in the controls, whereas sensitivity to hemodynamic changes after acetazolamide (ACZ) administration was assessed in the patients., Statistical Tests: Shapiro-Wilk, one-sample and paired-sample t-test, repeated measures ANOVA, mixed linear model, Bland-Altman analysis and correlation analysis. Sidak multiple-comparison correction was performed. Significance level was 0.05., Results: In controls, T 2 b from T 2 -TRIR (70 ± 11 msec) was higher compared to TRUST (60 ± 8 msec). In patients, T 2 b values were lower pre- compared to post-ACZ administration (TRUST: 80 ± 15 msec and 106 ± 23 msec and T 2 -TRIR: 95 ± 21 msec and 125 ± 36 msec). Consequently, Yv and OEF were lower and higher pre- compared to post-ACZ administration (TRUST Yv: 68% ± 7% and 77% ± 8%, T 2 -TRIR Yv: 74% ± 8% and 80% ± 6%, TRUST OEF: 30% ± 7% and 21% ± 8%, and T 2 -TRIR OEF: 25% ± 8% and 18% ± 6%)., Data Conclusion: TRUST and T 2 -TRIR are reproducible, but T 2 -TRIR-derived T 2 b values are significantly higher compared to TRUST, resulting in higher Yv and lower OEF estimates. This bias might be considered when evaluating cerebral oxygen homeostasis., Evidence Level: 2 TECHNICAL EFFICACY: Stage 2., (© 2022 International Society for Magnetic Resonance in Medicine.)

Type 2 diabetes causes substantial long-term damage in several organs including the brain. Cognitive decline is receiving increased attention as diabetes has been established as an independent risk factor along with the identification of several other pathophysiological mechanisms. Early detection of detrimental changes in cerebral blood flow regulation may represent a useful clinical marker for development of cognitive decline for at-risk persons. Technically, reliable evaluation of neurovascular coupling is possible with several caveats but needs further development before it is clinically convenient. Different modalities including ultrasound, positron emission tomography and magnetic resonance are used preclinically to shed light on the many influences on vascular supply to the brain. In this narrative review, we focus on the complex link between type 2 diabetes, cognition, and neurovascular coupling and discuss how the disease-related pathology changes neurovascular coupling in the brain from the organ to the cellular level. Different modalities and their respective pitfalls are covered, and future directions suggested., Competing Interests: MB has received honoraria as a speaker for Autonomic Technologies Inc. HS has received honoraria as speaker from Sanofi Genzyme, Denmark and Novartis, Denmark, as consultant from Sanofi Genzyme, Denmark, Lophora, Denmark, and Lundbeck AS, Denmark, and as editor-in-chief (Neuroimage Clinical) and senior editor (NeuroImage) from Elsevier Publishers, Amsterdam, The Netherlands. He has received royalties as book editor from Springer Publishers, Stuttgart, Germany and from Gyldendal Publishers, Copenhagen, Denmark. SM: Advisory boards: AstraZeneca; Boehringer Ingelheim; Eli Lilly; Merck Sharp & Dohme; Novo Nordisk; Sanofi, Bayer. Lecture fees: AstraZeneca; Boehringer Ingelheim; Merck Sharp & Dohme; Novo Nordisk; Sanofi. Research Grant Recipient: Novo Nordisk, Boehringer-Ingelheim. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Barloese, Bauer, Petersen, Hansen, Madsbad and Siebner.)

Radiostereometric analysis (RSA) is an accurate and precise radiographic method that can be used to measure micromotion of implants and study joint kinematics in vivo. A calibration cage with radiopaque markers is used to calibrate the RSA images; however, the thickness (250 mm) of the calibration cage restricts the available area for the patient and equipment during RSA recordings. A thinner calibration cage would increase the recording area, facilitate handling of the cage, and ease integration of the cage with the RSA system. We developed a thinner calibration cage without compromise of accuracy and precision. First, we performed numerical simulations of an RSA system, and showed that the calibration cage thickness could be decreased to 140 mm maintaining accuracy and precision using 40 fiducial and 30 control markers. Second, we constructed a new calibration cage (NRT cage) according to the simulation results. Third, we validated the new calibration cage against two state-of-the-art calibration cages (Umeaa cage and Leiden cage) in a phantom study. All cages performed similar for marker-based analysis, except for y-rotation, where the Umeaa cage (SD = 0.064 mm) was less precise compared to the NRT (SD = 0.038 mm) and Leiden cages (0.042 mm) (p = .01). For model-based analysis the NRT cage had superior precision for translations (SD ≤ 0.054 mm) over the Leiden cage (SD ≤ 0.118 mm) and Umeaa cage (SD ≤ 0.093 mm) (p < .01). The combined study confirmed that the new and thinner calibration cage maintained accuracy and precision at the level of existing thicker calibration cages., (© 2021 Orthopaedic Research Society. Published by Wiley Periodicals LLC.)

Background and Purpose: Foveal triangular fibrocartilage complex (TFCC) lesion may cause distal radioulnar joint (DRUJ) instability. Dynamic radiostereometry (dRSA) has been validated for objective measurement of DRUJ kinematics. We evaluated DRUJ kinematics by dRSA before surgery and 12 months following open foveal reinsertion of the TFCC in comparison with contralateral non-injured DRUJs., Patients and Methods: In a prospective cohort study, 21 patients (11 men) of mean age 34 years (22-50) with arthroscopically confirmed foveal TFCC lesion were evaluated preoperatively, and at 6 and 12 months after open foveal TFCC reinsertion with QDASH, PRWE, pain on NRS, and bilateral dRSA imaging during a patient active press test motion cycle, including a force-loaded downstroke and a release phase., Results: Preoperatively, the force-loaded part (> 2.3 kg; 95% CI 1.6-3.0) of the press test motion cycle (from 15% to 75%) revealed a more volar position of the ulnar head in the sigmoid notch (DRUJ position ratio) and increased distance in DRUJs with foveal TFCC lesion compared with the patients' contralateral non-injured DRUJ (p < 0.05). 6 months postoperatively, the DRUJ position was generally normalized and remained normalized at 12 months. However, the DRUJ distance remained higher on the injured side. 12 months postoperatively, patients reported less pain during activities, with improved QDASH and PRWE scores (p < 0.007)., Interpretation: DRUJ kinematics during the press test showed increased DRUJ translation to a more volar position of the ulnar head after foveal TFCC lesion compared with the contralateral non-injured DRUJs. Open foveal TFCC reinsertion had a stabilizing effect on DRUJ kinematics towards normalization, and improved patient-reported outcomes 6 and 12 months after surgery.

Anodal transcranial direct current stimulation (aTDCS) of primary motor hand area (M1-HAND) can enhance corticomotor excitability, but it is still unknown which current intensity produces the strongest effect on intrinsic neural firing rates and synaptic activity. Magnetic resonance imaging (MRI) combined with pseudo-continuous Arterial Spin Labeling (pcASL MRI) can map regional cortical blood flow (rCBF). The measured rCBF signal is sensitive to regional changes in neuronal activity due to neurovascular coupling. Therefore, concurrent TDCS and pcASL MRI may reveal the relationship between current intensity and TDCS-induced changes in overall firing rates and synaptic activity in the cortical target. Here we employed pcASL MRI to map acute rCBF changes during short-duration aTDCS of left M1-HAND. Using the rCBF response as a proxy for regional neuronal activity, we investigated if short-duration aTDCS produces an instantaneous dose-dependent rCBF increase in the targeted M1-HAND that may be useful for individual dosing. Nine healthy right-handed participants received 30 s of aTDCS at 0.5, 1.0, 1.5, and 2.0 mA with the anode placed over left M1-HAND and cathode over the right supraorbital region. Concurrent pcASL MRI at 3 T probed TDCS-related rCBF changes in the targeted M1-HAND. Movement-induced rCBF changes were also assessed. Apart from a subtle increase in rCBF at 0.5 mA, short-duration aTDCS did not modulate rCBF in the M1-HAND relative to no-stimulation periods. None of the participants showed a dose-dependent increase in rCBF during aTDCS, even after accounting for individual differences in TDCS-induced electrical field strength. In contrast, finger movements led to robust activation of left M1-HAND before and after aTDCS. Short-duration bipolar aTDCS does not produce consistant instantaneous dose-dependent rCBF increases in the targeted M1-HAND at conventional intensity ranges. Therefore, the regional hemodynamic response profile to short-duration aTDCS may not be suited to inform individual dosing of TDCS intensity., (© 2022. The Author(s).)

Background: Antipsychotic drugs are primarily efficacious in treating positive symptoms by blocking the dopamine D2 receptor, but they fail to substantially improve negative symptoms and cognitive deficits. The limited efficacy may be attributed to the fact that the pathophysiology of psychosis involves multiple neurotransmitter systems. In patients with chronic schizophrenia, memantine, a non-competitive glutamatergic NMDA receptor antagonist, shows promise for ameliorating negative symptoms and improving cognition. Yet, it is unknown how memantine modulates glutamate levels, and memantine has not been investigated in patients with first-episode psychosis., Aims: This investigator-initiated double-blinded randomized controlled trial is designed to (1) test the clinical effects on negative symptoms of add-on memantine to antipsychotic medication, and (2) neurobiologically characterize the responders to add-on memantine., Materials and Equipment: Antipsychotic-naïve patients with first-episode psychosis will be randomized to 12 weeks treatment with [amisulpride + memantine] or [amisulpride + placebo]. We aim for a minimum of 18 patients in each treatment arm to complete the trial. Brain mapping will be performed before and after 12 weeks focusing on glutamate and neuromelanin in predefined regions. Regional glutamate levels will be probed with proton magnetic resonance spectroscopy (MRS), while neuromelanin signal will be mapped with neuromelanin-sensitive magnetic resonance imaging (MRI). We will also perform structural and diffusion weighted, whole-brain MRI. MRS and MRI will be performed at an ultra-high field strength (7 Tesla). Alongside, participants undergo clinical and neuropsychological assessments. Twenty matched healthy controls will undergo similar baseline- and 12-week examinations, but without receiving treatment., Outcome Measures: The primary endpoint is negative symptom severity. Secondary outcomes comprise: (i) clinical endpoints related to cognition, psychotic symptoms, side effects, and (ii) neurobiological endpoints related to regional glutamate- and neuromelanin levels, and structural brain changes., Anticipated Results: We hypothesize that add-on memantine to amisulpride will be superior to amisulpride monotherapy in reducing negative symptoms, and that this effect will correlate with thalamic glutamate levels. Moreover, we anticipate that add-on memantine will restore regional white matter integrity and improve cognitive functioning., Perspectives: By combining two licensed, off-patent drugs, AMEND aims to optimize treatment of psychosis while investigating the memantine response. Alongside, AMEND will provide neurobiological insights to effects of dual receptor modulation, which may enable future stratification of patients with first-episode psychosis before initial antipsychotic treatment., Clinical Trial Registration: [ClinicalTrials.gov], identifier [NCT04789915]., Competing Interests: BE was part of the Advisory Board of Eli Lilly Denmark A/S, Janssen-Cilag, Lundbeck Pharma A/S, and Takeda Pharmaceutical Company Ltd; and has received lecture fees from Bristol-Myers Squibb, Boehringer Ingelheim, Otsuka Pharma Scandinavia AB, Eli Lilly Company, and Lundbeck Pharma A/S. HS has received honoraria as speaker from Sanofi Genzyme, Denmark and Novartis, Denmark, as consultant from Sanofi Genzyme, Denmark, and Lundbeck AS, Denmark, and as editor-in-chief (Neuroimage Clinical) and senior editor (NeuroImage) from Elsevier Publishers, Amsterdam, The Netherlands. He has received royalties as book editor from Springer Publishers, Stuttgart, Germany and from Gyldendal Publishers, Copenhagen, Denmark. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Sandström, Baltzersen, Marsman, Lemvigh, Boer, Bojesen, Nielsen, Lundell, Sulaiman, Sørensen, Fagerlund, Lahti, Syeda, Pantelis, Petersen, Glenthøj, Siebner and Ebdrup.)

Background: Parkinson's disease (PD) causes a loss of neuromelanin-positive, noradrenergic neurons in the locus coeruleus (LC), which has been implicated in nonmotor dysfunction., Objectives: We used "neuromelanin sensitive" magnetic resonance imaging (MRI) to localize structural disintegration in the LC and its association with nonmotor dysfunction in PD., Methods: A total of 42 patients with PD and 24 age-matched healthy volunteers underwent magnetization transfer weighted (MTw) MRI of the LC. The contrast-to-noise ratio of the MTw signal (CNR MTw ) was used as an index of structural LC integrity. We performed slicewise and voxelwise analyses to map spatial patterns of structural disintegration, complemented by principal component analysis (PCA). We also tested for correlations between regional CNR MTw and severity of nonmotor symptoms., Results: Mean CNR MTw of the right LC was reduced in patients relative to controls. Voxelwise and slicewise analyses showed that the attenuation of CNR MTw was confined to the right mid-caudal LC and linked regional CNR MTw to nonmotor symptoms. CNR MTw attenuation in the left mid-caudal LC was associated with the orthostatic drop in systolic blood pressure, whereas CNR MTw attenuation in the caudal most portion of right LC correlated with apathy ratings. PCA identified a bilateral component that was more weakly expressed in patients. This component was characterized by a gradient in CNR MTw along the rostro-caudal and dorso-ventral axes of the nucleus. The individual expression score of this component reflected the overall severity of nonmotor symptoms., Conclusion: A spatially heterogeneous disintegration of LC in PD may determine the individual expression of specific nonmotor symptoms such as orthostatic dysregulation or apathy. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson Movement Disorder Society., (© 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson Movement Disorder Society.)

Deadspace is the tissue and bony defect in a surgical wound after closure. This space is presumably poorly perfused favouring bacterial proliferation and biofilm formation. In arthroplasty surgery, an obligate deadspace surrounding the prosthesis is introduced and deadspace management, in combination with obtaining therapeutic prophylactic antibiotic concentrations, is important for limiting the risk of acquiring a periprosthetic joint infection (PJI). This study aimed to investigate cefuroxime distribution to an orthopaedic surgical deadspace in comparison with plasma and bone concentrations during two dosing intervals (8 h × 2). In a setup imitating shoulder arthroplasty surgery, but without insertion of a prosthesis, microdialysis catheters were placed for cefuroxime sampling in a deadspace in the glenohumeral joint and in cancellous bone of the scapular neck in eighteen pigs. Blood samples were collected as a reference. Cefuroxime was administered according to weight (20 mg/kg). The primary endpoint was time above the cefuroxime minimal inhibitory concentration of the free fraction of cefuroxime for Staphylococcus aureus ( f T > MIC (4 μg/mL)). During the two dosing intervals, mean f T > MIC (4 μg/mL) was significantly longer in deadspace (605 min) compared with plasma (284 min) and bone (334 min). For deadspace, the mean time to reach 4 μg/mL was prolonged from the first dosing interval (8 min) to the second dosing interval (21 min), while the peak drug concentration was lower and half-life was longer in the second dosing interval. In conclusion, weight-adjusted cefuroxime f T > MIC (4 μg/mL) and elimination from the deadspace was longer in comparison to plasma and bone. Our results suggest a deadspace consolidation and a longer diffusions distance, resulting in a low cefuroxime turn-over. Based on theoretical targets, cefuroxime appears to be an appropriate prophylactic drug for the prevention of PJI.

Objective: Patients with advanced knee osteoarthritis (KOA) frequently alter their gait patterns in an attempt to alleviate symptoms. Understanding the underlying pathomechanics and identifying KOA phenotypes are essential to improve treatments. We investigated kinematics in patients with KOA to identify subgroups of homogeneous knee joint kinematics., Method: A total of 66 patients with symptomatic KOA scheduled for total knee arthroplasty and 15 age-matched healthy volunteers with asymptomatic, non-arthritic knees were included. We used k-means clustering to divide patients into subgroups based on dynamic radiostereometry-assessed tibiofemoral joint kinematics. Clinical characteristics such as knee ligament lesions and KOA scores were graded by magnetic resonance imaging and radiographs, respectively., Results: We identified four clusters that were supported by clinical characteristics. The flexion group (n = 20) consisted primarily of patients with medial KOA. The abduction group (n = 17) consisted primarily of patients with lateral KOA. The anterior draw group (n = 10) was composed of patients with medial KOA, some degree of anterior cruciate ligament lesion and the highest KOA score. The external rotation group (n = 19) primarily included patients with medial collateral and posterior cruciate ligament lesions., Conclusion: Based on tibiofemoral gait patterns, patients with advanced KOA can be divided into four subgroups with specific clinical characteristics and different KOA-affected compartments. The findings add to our understanding of how knee kinematics may affect the patient's development of different types of KOA. This may inspire improved and more patient-specific treatment strategies in the future., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background  Measurement of in vivo distal radioulnar joint (DRUJ) pathomechanics during simple activities can represent the disability experienced by patients and may be useful in diagnostics of DRUJ instability. A first step is to describe the physiological normal limits for DRUJ kinematics in a reproducible and precise test setup, which was the aim of this study. Methods  DRUJ kinematics were evaluated in 33 participants with dynamic radiostereometry (RSA) while performing a standardized press test examination. AutoRSA software was used for image analyses. Computed tomography (CT) forearm bone models were generated, and standardized anatomical axes were applied to estimate kinematic outcomes including, DRUJ translation, DRUJ position ratio, and changes in ulnar variance. Repeatability of dynamic RSA press test double examinations was evaluated to estimate the precision and intraclass correlation coefficient (ICC) test-retest agreement. Results  The maximum force during the press test was 6.0 kg (95% confidence interval [CI]: 5.1-6.9), which resulted in 4.7 mm (95% CI: 4.2-5.1) DRUJ translation, DRUJ position ratio of 0.40 (95% CI: 0.33-0.44), and increase in ulnar variance of 1.1 mm (95% CI: 1.0-1.2). The mean maximum DRUJ translation leveled off after a 5 kg force application. The DRUJ translation ICC coefficient was 0.93 within a prediction interval of ± 0.53mm. Conclusions  This clinical study demonstrates the normal values of DRUJ kinematics and reports excellent agreement and high precision of the press tests examination using an automated noninvasive dynamic RSA imaging method based on patient-specific CT bone models. The next step is the application of the method in patients with arthroscopic verified triangular fibrocartilage complex injuries. Level of Evidence  This is a Level IV, case series study., Competing Interests: Conflict of Interest None declared., (Thieme. All rights reserved.)

Low-grade systemic inflammation contributes to ageing-related cognitive decline, possibly by triggering a neuroinflammatory response through glial activation. Using proton magnetic resonance spectroscopy ( 1 H-MRS) at 7T in normal human individuals from 18 to 79 years in a cross-sectional study, we previously observed higher regional levels of myo-inositol (mIns), total creatine (tCr) and total choline (tCho) in older than younger age groups. Moreover, visuo-spatial working memory (vsWM) correlated negatively with tCr and tCho in anterior cingulate cortex (ACC) and mIns in hippocampus and thalamus. As mIns, tCr and tCho are higher in glia than neurons, this suggest a potential in vivo connection between cognitive ageing and higher regional levels of glia-related metabolites. In the present study, we tested whether these metabolic differences may be related to low-grade systemic inflammation. In the same individuals, plasma concentrations of the proinflammatory markers C-reactive protein (CRP), interleukin 8 (IL-8), and tumour necrosis factor α (TNF-α) were measured on the same day as 1 H-MRS assessments. We tested whether CRP, IL-8, and TNF-α concentrations correlated with the levels of glia-related metabolites. CRP and IL-8, but not TNF-α, were higher in older (69-79 years) than younger (18-26 years) individuals. CRP correlated positively with thalamic mIns and negatively with vsWM. IL-8 correlated positively with ACC tCho and hippocampal mIns, but not with vsWM. Mediation analysis revealed an indirect effect of IL-8 on vsWM via ACC tCho. Together, these findings corroborate the role of glial cells, perhaps via their role in neuroinflammation, as part of the neurobiological link between systemic inflammation and cognitive ageing., (© 2021 International Society for Neurochemistry.)

The major inhibitory neurotransmitter gamma-aminobutyric acid (GABA) and the dominant antioxidant glutathione (GSH) both play a crucial role in brain functioning and are involved in several neurodegenerative and psychiatric diseases. Magnetic resonance spectroscopy (MRS) is a unique way to measure these neurometabolites non-invasively, but the measurement is highly sensitive to head movements, and especially in specific patient groups, motion stabilization in MRS could be valuable. Conventional MRS is acquired at relatively short echo times (TE), however, for unambiguous detection of GABA and GSH, spectral editing techniques are typically used. These depend on longer TEs and use frequency selective spectral editing pulses to separate the low-intensity peaks of GABA and GSH from overlapping resonances, but results in further increased motion sensitivity. Low-intensity metabolite peaks are usually edited one-by-one, however, simultaneous editing of multiple metabolites can be achieved using a Hadamard scheme, resulting in a substantial reduction in scan time. To investigate and correct for motion sensitivity in both conventional short-TE MRS (PRESS) and edited MRS (HERMES), we implemented a navigator-based prospective motion correction strategy including reacquisition of corrupted data. PRESS and HERMES spectra were acquired without motion, with motion with correction (repeated twice), and with motion without correction. Results indicate that when sufficient retrospective outlier removal is used, no significant differences in concentration and spectral quality were observed between motion conditions, even without prospective correction. HERMES spectral editing data showed to be more sensitive to motion, as significant differences in metabolite estimates and variability of spectral quality measures were observed for tCr, GABA+ and GSH when only retrospective outlier removal was applied. When using both prospective and retrospective correction, spectral quality was improved to almost the level of the no-motion acquisition. No differences in metabolite ratios for GABA and GSH could be observed when using motion correction. In conclusion, edited MRS showed to be more prone to motion artifacts, and prospective motion correction can restore most of the spectral quality in both conventional and edited MRS., (Copyright © 2021. Published by Elsevier Inc.)

Radiostereometic analysis (RSA) is a precise method for the functional assessment of joint kinematics. Traditionally, the method is based on tracking of surgically implanted bone markers and analysis is user intensive. We propose an automated method of analysis based on models generated from computed tomography (CT) scans and digitally reconstructed radiographs. The study investigates method agreement between marker-based RSA and the CT bone model-based RSA method for assessment of knee joint kinematics in an experimental setup. Eight cadaveric specimens were prepared with bone markers and bone volume models were generated from CT-scans. Using a mobile fixture setup, dynamic RSA recordings were obtained during a knee flexion exercise in two unique radiographic setups, uniplanar and biplanar. The method agreement between marker-based and CT bone model-based RSA methods was compared using bias and LoA. Results obtained from uniplanar and biplanar recordings were compared and the influence of radiographic setup was considered for clinical relevance. The automated method had a bias of -0.19 mm and 0.11° and LoA within ±0.42 mm and ±0.33° for knee joint translations and rotations, respectively. The model pose estimation of the tibial bone was more precise than the femoral bone. The radiographic setup had no clinically relevant effect on results. In conclusion, the automated CT bone model-based RSA method had a clinical precision comparable to that of marker-based RSA. The automated method is non-invasive, fast, and clinically applicable for functional assessment of knee kinematics and pathomechanics in patients., (© 2020 Orthopaedic Research Society. Published by Wiley Periodicals LLC.)

Background: A modular polyethylene (PE) inlay in total knee arthroplasty (TKA) may wear on both sides. PE particles may induce osteolysis, which can lead to implant loosening. The aim of this study was to determine if PE wear in monobloc TKA differs from that ofmodular TKA at 60-month follow-up., Patients and Methods: In a prospective, patient-blinded trial, 50 patients were randomized to hybrid TKA surgery with either acementless high-porosity trabecular-metal tibial component with a monobloc UHMWPE inlay (MONO-TM) or a cementless low-porosity screw-augmented titanium fiber-mesh tibial component with a modular UHMWPE inlay (MODULAR-FM). Radiostereometry was used to measure PE wear and tibial component migration., Results: At 60-monthfollow-up, mean PE wear of the medial compartment was 0.24 mm and 0.61 mm and mean PE wear of the lateral compartment was 0.31 mm and 0.82 mm for the MONO-TM and the MODULAR-FM groups, respectively (p < 0.01). The PE wear-rate was 0.05 mm (95% CI 0.03-0.08) in the MONO-TM group and 0.14 mm (95% CI 0.12-0.17) in the MODULAR-FM group (p < 0.01). Total translation at 60 months was mean 0.30 mm (95% CI 0.10-0.51) less (p < 0.01) for MONO-TM compared with MODULAR-FM tibial components. The majority of tibial components were stable (<0.2 mm MTPM) from 12 to 24-month and 24 to 60-month follow-up., Conclusion: At mid-term follow-up, monobloc PE inlay wear was approximately 40% of that of the modular PE inlay wear, which suggest that back-side wear of modular PE inlays is a significant contributor of PE wear in hybrid TKA., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Glutamate detection in pons and thalamus using proton magnetic resonance spectroscopy ( 1 H-MRS) after an intervention is of interest for studying various brain disorders. However, 1 H-MRS in these brain regions is challenging and time-consuming, especially in longitudinal study designs. 1 H-MRS of more cortical structures at the ultrahigh magnetic field strength of 7T yields an improved spectral output, including separation of the glutamate signal from the glutamine signal, in a shorter and more feasible scan time, as compared to conventional clinical field strengths. For this purpose, we compared the feasibility of 1 H-MRS at 3T and 7T in pons and thalamus by applying a longitudinal study design of repeated measures on same day and three separate days at both field strength in five healthy participants. Total 1 H-MRS acquisition time was reduced by a factor 3.75 for pons and by a factor 3 for thalamus at 7T as compared to 3T. We found higher spectral signal-to-noise ratio (SNR) ( p < 0.001), lower linewidth ( p = 0.001) and lower Cramér-Rao lower bounds (CRLB) ( p < 0.001) for the combined glutamate and glutamine signal (Glx) in thalamus at 7T as compared to 3T. In pons, CRLB of Glx and SNR were lower at 7T ( p = 0.002 and p = 0.006), with no differences in linewidth compared to 3T. Mean within-subject variability of Glx concentration estimates was lower at 7T compared to 3T for both pons and thalamus. At 7T, it was possible to assess glutamate and γ-aminobutyric acid (GABA) simultaneously in pons and thalamus. In conclusion, 1 H-MRS at 7T resulted in improved spectral quality while allowing shorter scan times than at 3T as well as estimation of the pure glutamate signal in pons and thalamus. This opens up the opportunity for multimodal study designs and multiregional subcortical 1 H-MRS research. Glutamate and GABA measurement at 7T in pons and thalamus is advantageous for future investigations of excitatory-inhibitory mechanisms in brain disorders., (Copyright © 2020 Younis, Hougaard, Christensen, Vestergaard, Petersen, Boer, Paulson, Ashina, Marsman and Larsson.)

Proton MR spectroscopy ( 1 H-MRS) has been used to assess regional neurochemical brain changes during normal ageing, but results have varied. Exploiting the increased sensitivity at ultra-high field, we performed 1 H-MRS in 60 healthy human volunteers to asses age-related differences in metabolite levels and their relation to cognitive ageing. Sex was balanced, and participants were assigned to a younger, middle, and older group according to their age, ranging from 18 to 79 years. They underwent 7T 1 H-MRS of the ACC, DLPFC, hippocampus, and thalamus and performed a visuospatial working memory task outside the scanner. A multivariate ANCOVA revealed a significant overall effect of age group on metabolite levels in all regions. Higher levels in the middle than the younger group were observed for myo-inositol (mIns) in DLPFC and hippocampus and total choline (tCho) in ACC. Higher levels in the older than the younger group were observed for mIns in hippocampus and thalamus, total creatine (tCr) and tCho in ACC and hippocampus; lower levels of glutamate (Glu) were observed in DLPFC. Higher levels in the older than the middle group were observed for mIns in hippocampus, tCr in ACC and hippocampus, tCho in hippocampus, and total N -acetyl aspartate (tNAA) in hippocampus. Working memory performance correlated negatively with tCr and tCho levels in ACC and mIns levels in hippocampus and thalamus, but not with tNAA or glutamate levels. As NAA and Glu are commonly regarded to reflect neuronal health and function and concentrations of mIns, tCr, and tCho are higher in glia than neurons, the findings of this study suggest a potential in vivo connection between cognitive ageing and higher regional levels of glia-related metabolites. SIGNIFICANCE STATEMENT Neurochemical ageing is an integral component of age-related cognitive decline. Proton MR spectroscopy ( 1 H-MRS) studies of in vivo neurochemical changes across the lifespan have, however, yielded inconclusive results. 1 H-MRS at ultra-high field strength can potentially improve the consistency of findings. Using 7T 1 H-MRS, we assessed levels of mIns, tCr, and tCho (glia-related metabolites) and tNAA and Glu (neuron-related metabolites) in ACC, DLPFC, hippocampus, and thalamus. We found higher levels of glia-related metabolites in all brain regions in older individuals. Working memory performance correlated negatively with regional levels of glia-related metabolites. This study is the first to investigate normal ageing in these brain regions using 7T 1 H-MRS and findings indicate that glia-related metabolites could be valuable in cognitive ageing studies., (Copyright © 2020 the authors.)

Cerebral cortical microinfarcts (CMIs) are small ischemic lesions associated with cognitive impairment and dementia. CMIs are frequently observed in cortical watershed areas suggesting that hypoperfusion contributes to their development. We investigated if presence of CMIs was related to a decrease in cerebral perfusion, globally or specifically in cortex surrounding CMIs. In 181 memory clinic patients (mean age 72 ± 9 years, 51% male), CMI presence was rated on 3-T magnetic resonance imaging (MRI). Cerebral perfusion was assessed from cortical gray matter of the anterior circulation using pseudo-continuous arterial spin labeling parameters cerebral blood flow (CBF) (perfusion in mL blood/100 g tissue/min) and spatial coefficient of variation (CoV) (reflecting arterial transit time (ATT)). Patients with CMIs had a 12% lower CBF (beta = -.20) and 22% higher spatial CoV (beta = .20) (both p  < .05) without a specific regional pattern on voxel-based CBF analysis. CBF in a 2 cm region-of-interest around the CMIs did not differ from CBF in a reference zone in the contralateral hemisphere. These findings show that CMIs in memory clinic patients are primarily related to global reductions in cerebral perfusion, thus shedding new light on the etiology of vascular brain injury in dementia.

Purpose: To interleave global and local higher order shimming for single voxel MRS. Single voxel MR spectroscopy requires optimization of the B 0 field homogeneity in the region of the voxel to obtain a narrow linewidth and provide high data quality. However, the optimization of local higher order fields on a localized MRS voxel typically leads to large field offsets outside that volume. This compromises interleaved MR sequence elements that benefit from global field homogeneity such as water suppression, interleaved MRS-fMRI, and MR motion correction., Methods: A shimming algorithm was developed to optimize the MRS voxel homogeneity and the whole brain homogeneity for interleaved sequence elements, using static higher order shims and dynamic linear terms (HOS-DLT). Shimming performance was evaluated using 6 brain regions and 10 subjects. Furthermore, the benefits of HOS-DLT was demonstrated for water suppression, MRS-fMRI, and motion corrected MRS using fat-navigators., Results: The HOS-DLT algorithm was shown to improve the whole brain homogeneity compared to an MRS voxel-based shim, without compromising the MRS voxel homogeneity. Improved water suppression over the brain, reduced image distortions in MRS-fMRI, and improved quality of motion navigators were demonstrated using the HOS-DLT method., Conclusion: HOS-DLT shimming allowed for both local and global field homogeneity, providing excellent MR spectroscopy data quality, as well as good field homogeneity for interleaved sequence elements, even without the need for dynamic higher order shimming capabilities., (© 2020 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine.)

Background: The Mohs Appropriate Use Criteria (MAUC) have come into question recently regarding the most appropriate treatment for superficial basal cell carcinoma (sBCC). At the heart of this debate is the limited body of evidence describing tumor behavior of sBCC based on clinical factors relevant to the MAUC., Objective: To determine whether sBCC is more likely to harbor aggressive subtypes in high-risk anatomical locations and in immunocompromised patients., Materials and Methods: A single institution retrospective review produced 133 evaluable Mohs cases performed on sBCC over a 10-year period. All slides from the respective cases were reviewed for the presence of histologic patterns other than known sBCC. Cases were then grouped by both MAUC anatomical zone (H, M, and L) and patient immune status for statistical analysis., Results: A significantly higher rate of mixed histology (MH) was observed when comparing Zone H with Zone L across all patients, healthy patients, and immunocompromised patients. The same was true when comparing Zone M with Zone L for all patients and healthy patients (immunocompromised did not reach significance)., Conclusion: The authors' data very clearly demonstrate a higher rate of MH in sBCC of the head and neck which provides strong support to the current MAUC scoring.

In sickle cell disease (SCD), oxygen delivery is impaired due to anemia, especially during times of increased metabolic demand, and cerebral blood flow (CBF) must increase to meet changing physiologic needs. But hyperemia limits cerebrovascular reserve (CVR) and ischemic risk prevails despite elevated CBF. The cerebral metabolic rate of oxygen (CMRO 2 ) directly reflects oxygen supply and consumption and may therefore be more insightful than flow-based CVR measures for ischemic risk in SCD. We hypothesized that adults with SCD have impaired CMRO 2 at rest and that a vasodilatory challenge with acetazolamide would improve CMRO 2 . CMRO 2 was calculated from CBF and oxygen extraction fraction (OEF), measured with arterial spin labeling and T 2 -prepared tissue relaxation with inversion recovery (T 2 -TRIR) MRI. We studied 36 adults with SCD without a clinical history of overt stroke, and nine healthy controls. As expected, CBF was higher in patients with SCD versus controls (mean ± SD: 74 ± 16 versus 46 ± 5 mL/100 g/min, P < .001), resulting in similar oxygen delivery (SCD: 377 ± 67 versus controls: 368 ± 42 μmol O 2 /100g/min, P = .69). OEF was lower in patients versus controls (27 ± 4 versus 35 ± 4%, P < .001), resulting in lower CMRO 2 in patients versus controls (102 ± 24 versus 127 ± 20 μmol O 2 /100g/min, P = .002). After acetazolamide, CMRO 2 declined further in patients (P < .01) and did not decline significantly in controls (P = .78), indicating that forcing higher CBF worsened oxygen utilization in SCD patients. This lower CMRO 2 could reflect variation between healthy and unhealthy vascular beds in terms of dilatory capacity and resistance whereby dysfunctional vessels become more oxygen-deprived, hence increasing the risk of localized ischemia., (© 2020 The Authors. American Journal of Hematology published by Wiley Periodicals, Inc.)

Purpose: To compare cerebral blood flow (CBF) and cerebrovascular reserve (CVR) quantification from Turbo-QUASAR (quantitative signal targeting with alternating radiofrequency labeling of arterial regions) arterial spin labeling (ASL) and single post-labeling delay pseudo-continuous ASL (PCASL)., Methods: A model-based method was developed to quantify CBF and arterial transit time (ATT) from Turbo-QUASAR, including a correction for magnetization transfer effects caused by the repeated labeling pulses. Simulations were performed to assess the accuracy of the model-based method. Data from an in vivo experiment conducted on a healthy cohort were retrospectively analyzed to compare the CBF and CVR (induced by acetazolamide) measurement from Turbo-QUASAR and PCASL on the basis of global and regional differences. The quality of the two ASL data sets was examined using the coefficient of variation (CoV)., Results: The model-based method for Turbo-QUASAR was accurate for CBF estimation (relative error was 8% for signal-to-noise ratio = 5) in simulations if the bolus duration was known. In the in vivo experiment, the mean global CVR estimated by Turbo-QUASAR and PCASL was between 63% and 64% and not significantly different. Although global CBF values of the two ASL techniques were not significantly different, regional CBF differences were found in deep gray matter in both pre- and postacetazolamide conditions. The CoV of Turbo-QUASAR data was significantly higher than PCASL., Conclusion: Both ASL techniques were effective for quantifying CBF and CVR, despite the regional differences observed. Although CBF estimated from Turbo-QUASAR demonstrated a higher variability than PCASL, Turbo-QUASAR offers the advantage of being able to measure and control for variation in ATT., (© 2019 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine.)

Advanced cutaneous squamous cell carcinoma (cSCC) accounts for only 5% of all cases of cSCC but up to 60% of disease related deaths. Historically, this disease has lacked effective treatment options due to a combination of poor response rate, poor response durability and significant treatment-associated morbidity. Autumn of 2018 marked the first time ever that an agent received US FDA approval for advanced cSCC and the future is looking much brighter for this previously neglected patient population. The purpose of this article is to review the various systemic treatment options for advanced cSCC moving from the past to the present, highlighting their relative merits and shortcomings, and to briefly speculate on future developments in the field of advanced cSCC.

Introduction: Subject movements lead to severe artifacts in magnetic resonance (MR) brain imaging. In this study we evaluate the diagnostic image quality in T1-weighted, T2-weighted, and time-of-flight angiographic MR sequences when using a flexible, navigator-based prospective motion correction system (iMOCO)., Methods: Five healthy volunteers were scanned during different movement scenarios with and without (+/-) iMOCO activated. An experienced neuroradiologist graded images for image quality criteria (grey-white-matter discrimination, basal ganglia, and small structure and vessel delineation), and general image quality on a four-grade scale., Results: In scans with deliberate motion, there was a significant improvement in the image quality with iMOCO compared to the scans without iMOCO in both general image impression (T1 p<0.01, T2 p<0.01, TOF p = 0.03) and in anatomical grading (T1 p<0.01, T2 p<0.01, TOF p = 0.01). Subjective image quality was considered non-diagnostic in 91% of the scans with motion -iMOCO, but only in 4% of the scans with motion +iMOCO. iMOCO performed best in the T1-weighted sequence and least well in the angiography sequence. iMOCO was not shown to have any negative effect on diagnostic image quality, as no significant difference in diagnostic quality was seen between scans -iMOCO and +iMOCO with no deliberate movement., Conclusion: The evaluation showed that iMOCO enables substantial improvements in image quality in scans affected by subject movement, recovering important diagnostic information in an otherwise unusable scan., Competing Interests: MA is an employee of Philips Danmark A/S.

Background: Sildenafil and calcitonin gene-related peptide both dilate the intradural segments of the middle meningeal artery measured with 3.0 tesla (T) MR angiography. Here we hypothesized that an increase in field strength to 7.0 T and concomitant enhanced voxel resolution would lower variance in measurements of dilation in the intradural middle meningeal artery., Methods: Five subjects completed two sessions at respectively 3.0 T and 7.0 T. Each session comprised MR angiography scans once before and twice after administration of sildenafil, calcitonin gene-related peptide or placebo in a three-way, crossover, double-blind, placebo-controlled design., Results: Standard deviations of arterial circumference revealed no difference between 3.0 T and 7.0 T measurements (p = 0.379). We found a decrease in standard deviation from our original angiography analysis software (QMra) to a newer (LAVA) software package (p < 0.001). Furthermore, we found that the dilation after sildenafil and calcitonin gene-related peptide were comparable between 3.0 T and 7.0 T., Conclusions: Our findings suggest no gain from the increase in voxel resolution but cemented dilatory findings from earlier. The implemented software update improved variance in circumference measurements in the intradural middle meningeal artery, which should be exploited in future studies., Trial Registration: The study is part of a parent study, which is registered at ClinicalTrials.gov ( NCT03143465 ).

Sickle cell disease is characterized by chronic hemolytic anemia and vascular inflammation, which can diminish the vasodilatory capacity of the small resistance arteries, making them less adept at regulating cerebral blood flow. Autoregulation maintains adequate oxygen delivery, but when vasodilation is maximized, the low arterial oxygen content can lead to ischemia and silent cerebral infarcts. We used magnetic resonance imaging of cerebral blood flow to quantify whole-brain cerebrovascular reserve in 36 adult patients with sickle cell disease (mean age, 31.9±11.3 years) and 11 healthy controls (mean age, 37.4±15.4 years), and we used high-resolution 3D FLAIR magnetic resonance imaging to determine the prevalence of silent cerebral infarcts. Cerebrovascular reserve was calculated as the percentage change in cerebral blood flow after a hemodynamic challenge with acetazolamide. Co-registered lesion maps were used to demonstrate prevalent locations for silent cerebral infarcts. Cerebral blood flow was elevated in patients with sickle cell disease compared to controls (median [interquartile range]: 82.8 [20.1] vs 51.3 [4.8] mL/100g/min, P <0.001). Cerebral blood flow was inversely associated with age, hemoglobin, and fetal hemoglobin, and correlated positively with bilirubin, and LDH, indicating that cerebral blood flow may reflect surrogates of hemolytic rate. Cerebrovascular reserve in sickle cell disease was decreased by half compared to controls (34.1 [33.4] vs 69.5 [32.4] %, P <0.001) and was associated with hemoglobin and erythrocyte count indicating anemia-induced hemodynamic adaptations. In total, 29/36 patients (81%) and 5/11 controls (45%) had silent cerebral infarcts (median volume of 0.34 vs 0.02 mL, P =0.03). Lesions were preferentially located in the borderzone. In conclusion, patients with sickle cell disease have a globally reduced cerebrovascular reserve as determined by arterial spin labeling with acetazolamide and reflects anemia-induced impaired vascular function in sickle cell disease. This study was registered at clinicaltrials.gov identifier 02824406 ., (Copyright© 2019 Ferrata Storti Foundation.)

Background: Sildenafil and calcitonin gene-related peptide are vasoactive substances that induce migraine attacks in patients. The intradural arteries are thought to be involved, but these have never been examined in vivo. Sildenafil is the only migraine-inducing compound for which cephalic, extracranial artery dilation is not reported. Here, we investigate the effects of sildenafil and calcitonin gene-related peptide on the extracranial and intradural parts of the middle meningeal artery., Methods: In a double-blind, randomized, three-way crossover, placebo-controlled head-to-head comparison study, MR-angiography was recorded in healthy volunteers at baseline and twice after study drug (sildenafil/ calcitonin gene-related peptide/saline) administration. Circumferences of extracranial and intradural middle meningeal artery segments were measured using semi-automated analysis software. The area under the curve for circumference change was compared using paired t-tests between study days., Results: Twelve healthy volunteers completed the study. The area under the curve Baseline-120min was significantly larger on both the sildenafil and the calcitonin gene-related peptide day in the intradural middle meningeal artery (calcitonin gene-related peptide, p = 0.013; sildenafil, p = 0.027) and the extracranial middle meningeal artery (calcitonin gene-related peptide, p = 0.0003; sildenafil, p = 0.021), compared to placebo. Peak intradural middle meningeal artery dilation was 9.9% (95% CI [2.9-16.9]) after sildenafil (T 30min ) and 12.5% (95% CI [8.1-16.8]) after calcitonin gene-related peptide (T 30min ). Peak dilation of the extracranial middle meningeal artery after calcitonin gene-related peptide (T 30min ) was 15.7% (95% CI [11.2-20.1]) and 18.9% (95% CI [12.8-24.9]) after sildenafil (T 120min )., Conclusion: An important novel finding is that both sildenafil and calcitonin gene-related peptide dilate intradural arteries, supporting the notion that all known pharmacological migraine triggers dilate cephalic vessels. We suggest that intradural artery dilation is associated with headache induced by calcitonin gene-related peptide and sildenafil.