Free-breathing abdominal chemical exchange saturation transfer imaging using water presaturation and respiratory gating at 3.0 T.

Free-breathing abdominal chemical exchange saturation transfer (CEST) has great potential for clinical application, but its technical implementation remains challenging. This study aimed to propose and evaluate a free-breathing abdominal CEST sequence. The proposed sequence employed respiratory gating (ResGat) to synchronize the data acquisition with respiratory motion and performed a water presaturation module before the CEST saturation to abolish the influence of respiration-induced repetition time variation. In vivo experiments were performed to compare different respiratory motion-control strategies and B0 offset correction methods, and to evaluate the effectiveness and necessity of the quasi-steady-state (QUASS) approach for correcting the influence of the water presaturation module on CEST signal. ResGat with a target expiratory phase of 0.5 resulted in a higher structural similarity index and a lower coefficient of variation on consecutively acquired CEST S0 images than breath-holding (BH) and respiratory triggering (all p < 0.05). B0 maps derived from the abdominal CEST dataset itself were more stable for B0 correction, compared with the separately acquired B0 maps by a dual-echo time scan and B0 maps derived from the water saturation shift referencing approach. Compared with BH, ResGat yielded more homogeneous magnetization transfer ratio asymmetry maps at 3.5 ppm (standard deviation: 3.96% vs. 3.19%, p = 0.036) and a lower mean squared difference between scan and rescan (27.52‱ vs. 16.82‱, p = 0.004). The QUASS approach could correct the water presaturation-induced CEST signal change, but its necessity for in vivo scanning needs further verification. The proposed free-breathing abdominal CEST sequence using ResGat had an acquisition efficiency of approximately four times that using BH. In conclusion, the proposed free-breathing abdominal CEST sequence using ResGat and water presaturation has a higher acquisition efficiency and image quality than abdominal CEST using BH.

Simultaneous T1, T2, and T2* Mapping of Carotid Plaque: The SIMPLE* Technique.

Background Quantitative T1, T2, and T2* measurements of carotid atherosclerotic plaque are important in evaluating plaque vulnerability and monitoring its progression. Purpose To develop a sequence to simultaneously quantify T1, T2, and T2* of carotid plaque. Materials and Methods The simultaneous T1, T2, and T2* mapping of carotid plaque (SIMPLE*) sequence is composed of three modules with different T2 preparation pulses, inversion-recovery pulses, and acquisition schemas. Single-echo data were used for T1 and T2 quantification, while the multiecho (ME) data were used for T2* quantification. The quantitative accuracy of SIMPLE* was tested in a phantom study by comparing its measurements with those of reference standard sequences. In vivo feasibility of the technique was prospectively evaluated between November 2020 and February 2022 in healthy volunteers and participants with carotid atherosclerotic plaque. The Pearson or Spearman correlation test, Student t test, and Wilcoxon rank-sum test were used. Results T1, T2, and T2* estimated with SIMPLE* strongly correlated with inversion-recovery spin-echo (SE) (correlation coefficient [r] = 0.99), ME-SE (r = 0.99), and ME gradient-echo (r = 0.99) sequences in the phantom study. In five healthy volunteers (mean age, 25 years ± 3 [SD]; three women), measurements were similar between SIMPLE* and modified Look-Locker inversion recovery, or MOLLI (1151 msec ± 71 vs 1098 msec ± 64; P = .14), ME turbo SE (31 msec ± 1 vs 31 msec ± 1; P = .32), and ME turbo field echo (24 msec ± 2 vs 25 msec ± 2; P = .19). In 18 participants with carotid plaque (mean age, 65 years ± 9; 16 men), quantitative T1, T2, and T2* of plaque components were consistent with their signal characteristics on multicontrast images. Conclusion A quantitative technique for simultaneous T1, T2, and T2* mapping of carotid plaque with 100-mm3 coverage and 0.8-mm3 resolution was developed using the proposed SIMPLE* sequence and demonstrated high accuracy and in vivo feasibility. © RSNA, 2023 Supplemental material is available for this article.

MRI Assessment of Renal Lipid Deposition and Abnormal Oxygen Metabolism of Type 2 diabetes Mellitus Based on mDixon-Quant.

BACKGROUND: Diabetic nephropathy (DN) is the main cause of end-stage renal failure. Multiecho Dixon-based imaging utilizes chemical shift for water-fat separation that may be valuable in detecting changes both fat and oxygen content of the kidney from a single dataset. PURPOSE: To investigate whether multiecho Dixon-based imaging can assess fat and oxygen metabolism of the kidney in a single breath-hold acquisition for patients with type 2 diabetes mellitus (DM). STUDY TYPE: Prospective. SUBJECTS: A total of 40 DM patients with laboratory examination of biochemical parameters and 20 age- and body mass index (BMI)-matched healthy volunteers (controls). FIELD STRENGTH/SEQUENCE: 3D multiecho Dixon gradient-echo sequence at 3.0 T. ASSESSMENT: The DM patients were divided into two groups based on urine albumin-to-creatinine ratio (ACR): type 2 diabetes mellitus (DM, 20 patients, ACR < 30 mg/g) and diabetic nephropathy (DN, 20 patients, ACR ≥ 30 mg/g). In all subjects, fat fraction (FF) and relaxation rate (R2*) maps were derived from the Dixon-based imaging dataset, and mean values in manually drawn regions of interest in the cortex and medulla compared among groups. Associations between MRI and biochemical parameters, including ß2-microglobulin, were investigated. STATISTICAL TESTS: Kruskal-Wallis tests, Spearman correlation analysis, and receiver operating characteristic (ROC) curve analysis. RESULTS: FF and R2* values of the renal cortex and medulla were significantly different among the three groups with control group < DM < DN (FF: control, 1.11± 0.30, 1.10 ± 0.39; DM, 1.52 ± 0.32, 1.57 ± 0.35; DN, 1.99 ± 0.66, 2.21 ± 0.59. R2*: Control, 16.88 ± 0.77, 20.70 ± 0.86; DM, 17.94 ± 0.75, 22.10 ± 1.12; DN, 19.20 ± 1.24, 23.63 ± 1.33). The highest correlation between MRI and biochemical parameters was that between cortex R2* and ß2-microglobulin (r = 0.674). A medulla R2* cutoff of 21.41 seconds-1 resulted in a sensitivity of 80%, a specificity of 85% and achieved the largest area under the ROC curve (AUC) of 0.83 for discriminating DM from the controls. A cortex FF of 1.81% resulted in a sensitivity of 80%, a specificity of 100% and achieved the largest AUC of 0.83 for discriminating DM from DN. DATA CONCLUSION: Multiecho Dixon-based imaging is feasible for noninvasively distinguishing DN, DM and healthy controls by measuring FF and R2* values. EVIDENCE LEVEL: 2. TECHNICAL EFFICACY: Stage 2.

Application of Quantitative MRI in Thyroid Eye Disease: Imaging Techniques and Clinical Practices.

Thyroid eye disease (TED) is a complex autoimmune disorder that impairs various orbital structures, leading to cosmetic damage and vision loss. Magnetic resonance imaging (MRI) is a fundamental diagnostic tool utilized in clinical settings of TED, for its accurate demonstration of orbital lesions and indication of disease conditions. The application of quantitative MRI has brought a new prospect to the management and research of TED, offering more detailed information on morphological and functional changes in the orbit. Therefore, many researchers concentrated on the implementation of different quantitative MRI techniques on TED for the exploration of clinical practices. Despite the abundance of studies utilizing quantitative MRI in TED, there remain considerable barriers and disputes on the best exploitation of this tool. This could possibly be attributed to the complexity of TED and the fast development of MRI techniques. It is necessary that clinical and radiological aspects of quantitative MRI in TED be better integrated into comprehensive insights. Hence, this review traces back 30 years of publications regarding quantitative MRI utilized in TED and elucidates this promising application in the facets of imaging techniques and clinical practices. We believe that a deeper understanding of the application of quantitative MRI in TED will enhance the efficacy of the multidisciplinary management of TED. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 3.

Inflow Angle Impacts Morphology, Hemodynamics, and Inflammation of Side-wall Intracranial Aneurysms.

BACKGROUND: Aneurysm inflow angle has been shown to be associated with hemodynamic changes by computational fluid dynamics. However, these studies were based on single aneurysm model and were limited to side-wall aneurysms. PURPOSE: To investigate the association between inflow angle and morphology, hemodynamic, and inflammation of intracranial side-wall and bifurcation aneurysms. STUDY TYPE: Prospective. POPULATION: A total of 62 patients (aged 58.34 ± 12.39, 44 female) with 59 unruptured side-wall aneurysms and 17 unruptured bifurcation aneurysms were included. FIELD STRENGTH/SEQUENCE: A 3.0 T; 3D fast field echo sequence (TOF-MRA); free-breathing, 3D radio-frequency-spoiled, multi-shot turbo field echo sequence (4D-flow MRI); 3D black-blood T1-weighted volumetric turbo spin echo acquisition sequence (T1 -VISTA) ASSESSMENT: Two neuroradiologists assessed the inflow angle and size for intracranial aneurysms in 3D space with TOF-MRA images. The average and maximum inflow velocity (Vavg-IA , Vmax-IA ), blood flow (Flowavg-IA , Flowmax-IA ), and average wall shear stress (WSSavg-IA ) for aneurysms were assessed from 4D-flow MRI in regions of interest drawn by two neuroradiologists. The aneurysmal wall enhancement (AWE) grades between precontrast and postcontrast T1 -VISTA images were evaluated by three neuroradiologists. STATISTICAL TESTS: Kruskal-Wallis H test, χ2 test, Pearson's correlation coefficient, scatter plots and regression lines, multivariate logistic regression analysis (partial correlation r) were performed. A P < 0.05 was considered statistically significant. RESULTS: The WSSavg-IA (0.52 ± 0.34 vs. 0.27 ± 0.22) and AWE grades (1.38 ± 1.04 vs. 2.02 ± 0.68) between the two inflow angle subgroups of side-wall aneurysms were significantly different. The aneurysm size (rs  = 0.31), WSSavg-IA (rs  = -0.45), and AWE grades (rs  = 0.45) were significantly correlated with inflow angle in side-wall aneurysms. While in bifurcation aneurysms, there were no significant associations between inflow angle and size (P = 0.901), Vavg-IA (P = 0.699), Vmax-IA (P = 0.482), Flowavg-IA (P = 0.550), Flowmax-IA (P = 0.689), WSSavg-IA (P = 0.573), and AWE grades (P = 0.872). DATA CONCLUSION: A larger aneurysm size, a lower WSS and a higher AWE grade were correlated with a larger inflow angle in side-wall aneurysms. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 2.

Identification and analysis of key hypoxia- and immune-related genes in hypertrophic cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy (HCM), an autosomal dominant genetic disease, is the main cause of sudden death in adolescents and athletes globally. Hypoxia and immune factors have been revealed to be related to the pathology of HCM. There is growing evidence of a role for hypoxia and inflammation as triggers and enhancers in the pathology in HCM. However, the role of hypoxia- and immune-related genes in HCM have not been reported. METHODS: Firstly, we obtained four HCM-related datasets from the Gene Expression Omnibus (GEO) database for differential expression analysis. Immune cells significantly expressed in normal samples and HCM were then screened by a microenvironmental cell population counter (MCP-counter) algorithm. Next, hypoxia- and immune-related genes were screened by the LASSO + support vector machine recursive feature elimination (SVM-RFE) and weighted gene co-expression network analysis (WGCNA). Single-gene enrichment analysis and expression validation of key genes were then performed. Finally, we constructed a competing endogenous RNA (ceRNA) network of key genes. RESULTS: In this study, 35 differentially expressed hypoxia genes were found. By using LASSO + SVM-RFE analysis, 10 more targets with differentially expressed hypoxia genes were identified. The MCP-count algorithm yielded five differentially expressed immune cells, and after assessing them for WGCNA characteristics, 612 immune genes were discovered. When hypoxia and immune genes were combined for cross-tabulation analysis, three hypoxia- and immune-related genes (ATP2A2, DDAH1, and OMA1) were identified. CONCLUSION: Based on hypoxia characteristic genes, three key genes were identified. These were also significantly related to immune activation, which proves a theoretical basis and reference value for studying the relationship between HCM and hypoxia and immunity.

Part 1: Evaluating Neck-Strengthening Protocols to Reduce the Incidence of Traumatic Brain Injury: Traditional vs. Nontraditional Neck-Strengthening Techniques.

ABSTRACT: Schroeder, LH, McDaniel, AT, Wang, Y, Dickens, GM, Pantani, V, and Kubinak, H. Part 1: evaluating neck-strengthening protocols to reduce the incidence of traumatic brain injury: traditional vs. nontraditional neck-strengthening techniques. J Strength Cond Res 38(1): 21-29, 2024-A common cause of traumatic brain injuries (TBIs) is the head's kinematic response to rapid movement, which can be reduced with dynamic neck strengthening. This study aimed to determine the most effective neck-strengthening program by comparing a traditional and nontraditional program. Isometric neck strength was assessed in 32 subjects randomly assigned to one of the traditional and nontraditional neck-strengthening programs. The nontraditional program used a novel neck-strengthening device. After weeks 6 and 10 of training, isometric neck strength was reassessed. With the collected data, linear mixed models were established to compare the changes in neck strength between the 2 groups during the 10-week training period. Statistical analysis results suggest that, for both cervical extension (CE) and cervical flexion (CF), subjects in the novel neck-strengthening device group had a significantly higher gain of strength during the 10 weeks than the traditional group. With test statistics of -2.691 and -3.203 and corresponding 2-sided p-value of 0.01289 and 0.003889, respectively, we conclude that there is a statistically significant difference in the linear slopes of increase for both CE and CF between the 2 groups. As to left cervical lateral flexion and right cervical lateral flexion, the novel neck strength group had increased strength gains compared with the traditional group. However, the increase was not enough to demonstrate significant findings. Results were considered significant at p < 0.05. The results of this study show that the novel neck-strengthening device may be an effective mechanism for preventing mild TBIs.

Optimization of the Contrast Agent Injection Protocol for Carotid Artery Dynamic Contrast-Enhanced Magnetic Resonance Imaging.

BACKGROUND: The injection protocol used in previous carotid artery dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) studies varied. PURPOSE: To investigate the effect of contrast injection protocol and optimize this protocol for carotid artery DCE-MRI. STUDY TYPE: Prospective. SUBJECTS: Digital phantom and seven patients with carotid atherosclerosis. FIELD STRENGTH/SEQUENCE: 3 T, spoiled gradient recalled echo sequence. ASSESSMENT: Different injection doses (0.01-0.3 mmol/kg) and effective injection rates (0.01-1 mmol/sec) were tested using a digital carotid plaque phantom considering the contrast pharmacokinetics, DCE-MRI imaging, contrast variation and flow-related imaging artifacts, random time delay between the contrast injection and image acquisition, and pharmacokinetic analysis process. For each injection protocol, combining the root mean square relative error (RMSRE) of the measured K trans and v P maps within the adventitial vasa vasorum from 10 tested time delays by the root mean square produced RMSREoverall-vv which was used to measure the overall accuracy of the pharmacokinetic parameters. In vivo validation was performed on seven patients with carotid atherosclerosis by imaging them twice using the traditional commonly used protocol and the recommended protocol found by simulation. STATISTICAL TEST: Student's t-test, chi-square test, and paired t-test, P < 0.05 was considered statistically significant. RESULTS: A low region of RMSREoverall-vv with the combination of medium injection dose and low effective injection rate was found. The protocol with injection dose of 0.07 mmol/kg and effective injection rate of 0.06 mmol/sec achieved the minimal RMSREoverall-vv (4.29%), thus was recommended, which showed more accurate arterial input function. Coinciding with the simulation results, this recommended protocol in in vivo experiments produced significantly fewer image artifacts, lower K trans and v P (P all <0.05) than traditional protocol which overestimated these parameters in simulation. DATA CONCLUSION: The contrast injection protocol influenced the accuracy of the pharmacokinetics parameter estimation in carotid artery DCE-MRI. The injection protocol with injection dose of 0.07 mmol/kg and effective injection rate of 0.06 mmol/sec was recommended. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 1.

High-fidelity diffusion tensor imaging of the cervical spinal cord using point-spread-function encoded EPI.

Diffusion tensor imaging (DTI) of the spinal cord is technically challenging due to the size of its structure and susceptibility-induced field inhomogeneity, which impedes clinical applications. This study aimed to achieve high-fidelity spinal cord DTI with reasonable SNR and practical acquisition efficiency. Particularly, a distortion-free multi-shot EPI technique, namely point-spread-function encoded EPI (PSF-EPI), was adopted for diffusion imaging of the cervical spinal cord (CSC). The shot number can be reduced to six for sagittal scans through titled-CAIPI acceleration and partial Fourier undersampling, consequently rendering this technique beneficial in clinics. Fifteen healthy volunteers and seven patients with metallic implants underwent sagittal scans using tilted-CAIPI PSF-EPI at 3T. Unsuppressed fat signals were further removed by retrospective water/fat separation using the intrinsic chemical-shift encoded signals. Compared with multi-shot interleaved EPI method, highly accelerated PSF-EPI method provided evidently improved distortion reduction and higher consistency with anatomical references even with metallic implants. Additionally, axial DTI scans using PSF-EPI were also evaluated quantitatively, and the measured DTI metrics are similar to those obtained from the zonal oblique multi-slice EPI (ZOOM-EPI) method and reported values. The high anatomical consistency, practical scan time and quantitative reliability indicate PSF-EPI's clinical potential for CSC diffusion imaging.

Association of metformin monotherapy or combined therapy with cardiovascular risks in patients with type 2 diabetes mellitus.

BACKGROUND: Metformin is a first-line drug in type 2 diabetes mellitus (T2DM) treatment, yet whether metformin may increase all-cause or cardiovascular mortality of T2DM patients remains inconclusive. METHODS: We searched PubMed and Embase for data extracted from inception to July 14, 2020, with a registration in PROSPERO (CRD42020177283). This study included randomized controlled trials (RCT) assessing the cardiovascular effects of metformin for T2DM. This study is followed by PRISMA and Cochrane guideline. Risk ratio (RR) with 95% CI was pooled across trials by a random-effects model. Primary outcomes include all-cause mortality and cardiovascular mortality. RESULTS: We identified 29 studies that randomly assigned patients with 371 all-cause and 227 cardiovascular death events. Compared with untreated T2DM patients, metformin-treated patients was not associated with lower risk of all-cause mortality (RR: 0.98; 95%CI: 0.69-1.38; P = 0.90), cardiovascular mortality (RR: 1.13; 95% CI: 0.60, 2.15; P = 0.70), macrovascular events (RR: 0.87; 95%CI: 0.70-1.07; P = 0.19), heart failure (RR: 1.02; 95% CI:0.61-1.71; P = 0.95), and microvascular events (RR: 0.78; 95% CI:0.54-1.13; P = 0.19). Combination of metformin with another hypoglycemic drug was associated with higher risk of all-cause mortality (RR: 1.49; 95% CI: 1.02, 2.16) and cardiovascular mortality (RR: 2.21; 95% CI: 1.22, 4.00) compared with hypoglycemic drug regimens with no metformin. CONCLUSION: The combination of metformin treatment may impose higher risk in all-cause and cardiovascular mortality. This finding, at least in part, shows no evidence for benefits of metformin in combination in terms of all-cause/cardiovascular mortality and cardiovascular events for T2DM. However, the conclusion shall be explained cautiously considering the limitations from UK Prospective Diabetes Study (UKPDS).

Distortion correction of single-shot EPI enabled by deep-learning.

PURPOSE: A distortion correction method for single-shot EPI was proposed. Point-spread-function encoded EPI (PSF-EPI) images were used as the references to correct traditional EPI images based on deep neural network. THEORY AND METHODS: The PSF-EPI method can obtain distortion-free echo planar images. In this study, a 2D U-net based network was trained to achieve the distortion correction of single-shot EPI (SS-EPI) images, using PSF-EPI images as targets in the training stage. Anatomical T2W-TSE images were also fed into the network to improve the quality of the results. The applications in diffusion-weighted images were used as examples in this work. The network was trained on data acquired on healthy volunteers and tested on data of both healthy volunteers and patients. The corrected EPI images from the proposed method were also compared with those from field-mapping and top-up based distortion correction methods. RESULTS: Experimental results showed that the proposed method can correct for EPI distortions better than both the field-mapping and top-up based methods, and the results were close to the distortion-free images from PSF-EPI. Additionally, inclusion of T2W-TSE images helped improve distortion correction of the SS-EPI images without contaminating the output noticeably. The experiments with patients and different MRI platforms demonstrated the generalization feasibility of the proposed method preliminarily. CONCLUSION: Through the correction of diffusion-weighted images, the proposed deep-learning based method was demonstrated to have the feasibility to correct for the distortion of EPI images.

Water/fat separation for distortion-free EPI with point spread function encoding.

PURPOSE: Effective removal of chemical-shift artifacts in echo-planar imaging (EPI) is a challenging problem especially with severe field inhomogeneity. This study aims to develop a reliable water/fat separation technique for point spread function (PSF) encoded EPI (PSF-EPI) by using its intrinsic multiple echo-shifted images. THEORY AND METHODS: EPI with PSF encoding can achieve distortion-free imaging and can be highly accelerated using the tilted-CAIPI technique. In this study, the chemical-shift encoding existing in the intermediate images with different time shifts of PSF-EPI is used for water/fat separation, which is conducted with latest water/fat separation algorithms. The method was tested in T1-weighted, T2-weighted, and diffusion weighted imaging in healthy volunteers. RESULTS: The ability of the proposed method to separate water/fat using intrinsic PSF-EPI signals without extra scans was demonstrated through in vivo T1-weighted, T2-weighted, and diffusion weighted imaging experiments. By exploring different imaging contrasts and regions, the results show that this PSF-EPI based method can separate water/fat and remove fat residues robustly. CONCLUSION: By using the intrinsic signals of PSF-EPI for water/fat separation, fat signals can be effectively suppressed in EPI even with severe field inhomogeneity. This water/fat separation method for EPI can be extended to multiple image contrasts. The distortion-free PSF-EPI technique, thus, has the potential to provide anatomical and functional images with high-fidelity and practical acquisition efficiency.

Distortion correction for high-resolution single-shot EPI DTI using a modified field-mapping method.

PURPOSE: The widely used single-shot EPI (SS-EPI) diffusion tensor imaging (DTI) suffers from strong image distortion due to B0 inhomogeneity, especially for high-resolution imaging. Traditional methods such as the field-mapping method and the top-up method have various deficiencies in high-resolution SS-EPI DTI distortion correction. This study aims to propose a robust distortion correction approach, which combines the advantages of traditional methods and overcomes their deficiencies, for high-resolution SS-EPI DTI. METHODS: The proposed correction method is based on the echo planar spectroscopic imaging field-mapping followed by an intensity correction procedure. To evaluate the efficacy of distortion correction, the proposed method was compared with the conventional field-mapping method and the top-up method, using a newly developed quantitative evaluation framework. The correction results were also compared with multi-shot EPI DTI to investigate whether the proposed method can provide high-resolution SS-EPI DTI with high geometric fidelity and high time efficiency. RESULTS: The results show that accurate field-mapping and intensity correction are critical to distortion correction in high-resolution SS-EPI DTI. The proposed method can provide more precise field maps and better correction results than the other two methods (p < 0.0001), and the corrected images show higher geometric fidelity than those from MS-EPI DTI. CONCLUSION: An effective method is proposed to reduce image distortion in high-resolution SS-EPI DTI. It is practical to achieve high-resolution DTI with high time efficiency and high structure accuracy using this method.

Melatonin attenuates chronic pain related myocardial ischemic susceptibility through inhibiting RIP3-MLKL/CaMKII dependent necroptosis.

Chronic pain aggravates cardiovascular injury via incompletely understood mechanisms. While melatonin may participate in the pathophysiological process of chronic pain, its cardiovascular effects under chronic pain states remains unknown. In this study, chronic pain was induced by spared nerve injury model (SNI) for 4 weeks. We showed decreased the ipsilateral hind paw withdrawal mechanical threshold (PWMT) in SNI mice. High dose melatonin treatment (60 mg/kg, i.p.) could reversed nociceptive threshold in SNI mice. To verify the effect of chronic pain on the cardiac tolerance to ischemic stress, mice were subjected to myocardial ischemia-reperfusion (MI/R) in vivo. SNI mice showed exaggerated MI/R-induced detrimental effects and myocardial necroptosis compared with control group (P < .05). Mechanically, an increased level of tumor necrosis factor-α (TNF-α) was found in SNI group following by a robust interaction of RIP1/RIP3. RIP3-induced phosphor-MLKL and CaMKII more significantly in SNI mice (P < .05). We found that RIP3 deficiency provided a comparable protection against MI/R-induced necroptosis under chronic pain conditions. More importantly, low dose melatonin (20 mg/kg, i.p.) treatment 10 min before reperfusion decreased the level of TNF-α following with a negatively regulating the RIP3 induced phosphor-MLKL/CaMKII signaling, thus significantly reduced ROS production and cardiomyocyte necroptosis and ameliorated cardiac function. In summarize, our results demonstrated that chronic pain sensitizes heart to MI/R injury and myocardial necrosis plays an important role in this pathophysiological process. We also define melatonin acted as triple cardioprotective effects: ameliorating TNF-α level, suppressing RIP3-MLKL/CaMKII signaling induced necroptosis and exerting analgesia effect.

Carotid Intraplaque Hemorrhage Imaging with Quantitative Vessel Wall T1 Mapping: Technical Development and Initial Experience.

Purpose To develop a three-dimensional (3D) high-spatial-resolution time-efficient sequence for use in quantitative vessel wall T1 mapping. Materials and Methods A previously described sequence, simultaneous noncontrast angiography and intraplaque hemorrhage (SNAP) imaging, was extended by introducing 3D golden angle radial k-space sampling (GOAL-SNAP). Sliding window reconstruction was adopted to reconstruct images at different inversion delay times (different T1 contrasts) for voxelwise T1 fitting. Phantom studies were performed to test the accuracy of T1 mapping with GOAL-SNAP against a two-dimensional inversion recovery (IR) spin-echo (SE) sequence. In vivo studies were performed in six healthy volunteers (mean age, 27.8 years ± 3.0 [standard deviation]; age range, 24-32 years; five male) and five patients with atherosclerosis (mean age, 66.4 years ± 5.5; range, 60-73 years; five male) to compare T1 measurements between vessel wall sections (five per artery) with and without intraplaque hemorrhage (IPH). Statistical analyses included Pearson correlation coefficient, Bland-Altman analysis, and Wilcoxon rank-sum test with data permutation by subject. Results Phantom T1 measurements with GOAL-SNAP and IR SE sequences showed excellent correlation (R2 = 0.99), with a mean bias of -25.8 msec ± 43.6 and a mean percentage error of 4.3% ± 2.5. Minimum T1 was significantly different between sections with IPH and those without it (mean, 371 msec ± 93 vs 944 msec ± 120; P = .01). Estimated T1 of normal vessel wall and muscle were 1195 msec ± 136 and 1117 msec ± 153, respectively. Conclusion High-spatial-resolution (0.8 mm isotropic) time-efficient (5 minutes) vessel wall T1 mapping is achieved by using the GOAL-SNAP sequence. This sequence may yield more quantitative reproducible biomarkers with which to characterize IPH and monitor its progression. © RSNA, 2017.

Segmentation of gray matter, white matter, and CSF with fluid and white matter suppression using MP2RAGE.

BACKGROUND: MP2RAGE can generate uniform T1 -weighted images, which have been used for brain segmentation. However, there remain concerns about carrying out fast brain segmentation. PURPOSE: To propose an acquisition-based method for fast segmentation of gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF) of healthy human brains with fluid and white matter suppression (FLAWS) using MP2RAGE. STUDY TYPE: Prospective. SUBJECTS: 12 volunteers (23-28 years, seven subjects; 51-62 years, five subjects). FIELD STRENGTH/SEQUENCES: 3T/3D MPRAGE and FLAWS. ASSESSMENT: The proposed method was evaluated by calculating tissue volumes and the spatial overlap with the segmentation results from FSL and SPM12. The processing time was recorded. STATISTICAL TESTS: A paired t-test was used to compare the tissue volumes of the proposed method with those from other segmentation methods RESULTS: For the 12 subjects, the tissue volume difference between the proposed and SPM12 were 3.2 ± 2.8%, 4.2 ± 2.5%, 18.2 ± 13.1% for GM, WM, and CSF, respectively. The relative difference between the proposed and FSL was over 14% for all tissue classes. The spatial overlap between the proposed and other methods were 87-94% for GM and WM and less than 80% for CSF. The GM and WM volumes of the proposed method were not significantly different from those of SPM12 using MPRAGE as the input (P = 0.5540 and P = 0.3115, respectively). The rest of the comparisons all showed significant differences between the proposed and other methods. Statistical analysis of the two subgroups yielded similar results. The mean processing time of one subject was 6.5, 185, and 165 seconds for the proposed method, FSL, and SPM12, respectively. DATA CONCLUSION: Our method may be accurate for the segmentation of most brain structures using FLAWS. In addition, the proposed method is fast and applicable to the two distinct age ranges. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2018;48:1540-1550.

Three-dimensional free breathing whole heart cardiovascular magnetic resonance T1 mapping at 3 T.

BACKGROUND: This study demonstrates a three-dimensional (3D) free-breathing native myocardial T1 mapping sequence at 3 T. METHODS: The proposed sequence acquires three differently T1-weighted volumes. The first two volumes receive a saturation pre-pulse with different recovery time. The third volume is acquired without magnetization preparation and after a significant recovery time. Respiratory navigator gating and volume-interleaved acquisition are adopted to mitigate misregistration. The proposed sequence was validated through simulation, phantom experiments and in vivo experiments in 12 healthy adult subjects. RESULTS: In phantoms, good agreement on T1 measurement was achieved between the proposed sequence and the reference inversion recovery spin echo sequence (R2 = 0.99). Homogeneous 3D T1 maps were obtained from healthy adult subjects, with a T1 value of 1476 ± 53 ms and a coefficient of variation (CV) of 6.1 ± 1.4% over the whole left-ventricular myocardium. The averaged septal T1 was 1512 ± 60 ms with a CV of 2.1 ± 0.5%. CONCLUSION: Free-breathing 3D native T1 mapping at 3 T is feasible and may be applicable in myocardial assessment. The proposed 3D T1 mapping sequence is suitable for applications in which larger coverage is desired beyond that available with single-shot parametric mapping, or breath-holding is unfeasible.

The first Australian Baseline Series: Recommendations for patch testing in suspected contact dermatitis.

BACKGROUND AND OBJECTIVES: Patch testing is a standard diagnostic tool used in the identification of causative allergens in allergic contact dermatitis. Ongoing surveillance of rates of allergen positivity is vitally important to detect trends and allow comparisons between countries. The objective of this study was to propose the first evidence-based Australian baseline series, based on retrospective review of our patch test data. We aimed to identify the most important and most relevant allergens in our population. METHODS: We conducted a 10-year (2001-2010) retrospective review of data from the contact dermatitis clinic and the occupational dermatitis clinic from our institution. RESULTS: We patch tested 5281 patients in all. The top 20 allergens with the highest number of relevant positive patch test reactions were: fragrance mix 1: nickel, potassium dichromate, Myroxylon pereirae, formaldehyde, p-phenylenediamine (PPD), thiuram mix, colophony (rosin), dermatophagoides mix, ammonium persulfate, quaternium-15, cobalt chloride, methylchloroisothiazolinone or methylisothiazolinone, diazolidinylurea, epoxy resin, 1,3-dimethylol-5,5-dimethyl hydantoin, Compositae mix, toluenesulfonamide formaldehyde resin, basic red 46 and imidazolidinyl urea. CONCLUSION: We have elucidated the most frequent and relevant contact allergens in our patient population and used this information to construct the first Australian baseline series.

Melatonin enhanced the cardioprotective effects of HTK solution on Langendorff-perfused mouse hearts subjected to ischemia/reperfusion.

Objectives: Cardiac arrest is a crucial procedure in various cardiac surgeries, during which the heart is subjected to an ischemic state. The occurrence of ischemia/reperfusion (I/R) injury is inevitable due to aortic blockage and opening. The Histidine-tryptophan-ketoglutarate (HTK) solution is commonly used as an organ protection liquid to mitigate cardiac injury during cardiac surgery. Despite its widespread use, there is significant potential for improving its protective efficacy. Materials and Methods: The cardioprotective effect of HTK solution with and without melatonin was evaluated using the isolated Langendorff-perfused mouse heart model. The isolated C57bL/6 mouse hearts were randomly divided into four groups: control, I/R, HTK solution treatment before reperfusion (HTK+I/R), and HTK solution combined with melatonin before reperfusion (HTK+M+I/R). Cardiac function and myocardial injury markers were then measured. AMP-activated protein kinase α2 (AMPKα2) KO mice were used to investigate the underlying mechanism. Results: In our study, we found that melatonin significantly improved the protective effects of HTK solution in an isolated Langendorff-perfused mouse model, mechanistically by reducing mitochondrial damage, improving energy metabolism, inhibiting cardiomyocyte apoptosis, and reducing myocardial infarction size. We also observed that the HTK solution alone was ineffective in inhibiting ER stress, but when melatonin was added, there was a significant reduction in ER stress. Furthermore, melatonin was found to alleviate carbonyl stress during cardiac I/R. Interestingly, our results showed that the cardioprotective properties of melatonin were dependent on AMPKα2. Conclusion: The findings presented in this study offer a valuable empirical foundation for the development of perioperative cardioprotective strategies.

Double lung transplantation is better than single lung transplantation for end-stage chronic obstructive pulmonary disease: a meta-analysis.

BACKGROUND: Lung transplantation is one of the most common treatment options for patients with end-stage chronic obstructive pulmonary disease. However, the choice between single and double lung transplantation for these patients remains a matter of debate. Therefore, we performed a systematic search of medical databases for studies on single lung transplantation, double lung transplantation, and chronic obstructive pulmonary disease. METHODS: The rate ratio and hazard ratio of survival were analyzed. The meta-analysis included 15 case-control and retrospective registry studies. RESULTS: The rate ratios of the 3-year survival (0.937 and P = 0.041) and 5-year survival (0.775 and P = 0.000) were lower for single lung transplantation than for double lung transplantation. However, the hazard ratio did not differ significantly between the two. CONCLUSIONS: Double lung transplantation was found to provide better benefits than single lung transplantation in terms of the long-term survival in patients with chronic obstructive pulmonary disease.