Muscle Ratio Research Articles

Kinetic Analysis and Metabolism of Poly(Adenosine Diphosphate-Ribose) Polymerase-1-Targeted 18F-Fluorthanatrace PET in Breast Cancer.

The poly(adenosine diphosphate-ribose) polymerase inhibitors (PARPi) have demonstrated efficacy in ovarian, breast, and prostate cancers, but current biomarkers do not consistently predict clinical benefit. 18F-fluorthanatrace (18F-FTT) is an analog to rucaparib, a clinically approved PARPi, and is a candidate biomarker for PARPi response. This study intends to characterize 18F-FTT pharmacokinetics in breast cancer and optimize image timing for clinical trials. A secondary aim is to determine whether 18F-FTT uptake in breast cancer correlates with matched frozen surgical specimens as a reference standard for PARP-1 protein. Methods: Thirty prospectively enrolled women with a new diagnosis of breast cancer were injected with 18F-FTT and imaged dynamically 0-60 min after injection over the chest, with an optional static scan over multiple bed positions starting around 70 min. Kinetic analysis of lesion uptake was performed using blood-pool activity with population radiometabolite corrections. Normal breast and normal muscle reference tissue models were compared with PARP-1 protein expression in 10 patients with available tissue. Plasma radiometabolite concentrations and uptake in tumor and normal muscle were investigated in mouse xenografts. Results: Pharmacokinetics of 18F-FTT were well fit by Logan plot reference region models of reversible binding. However, fits of 2-tissue compartment models assuming negligible metabolite uptake were unstable. Rapid metabolism of 18F-FTT was demonstrated in mice, and similar uptake of radiometabolites was found in tumor xenografts and normal muscle. Tumor 18F-FTT distribution volume ratios relative to normal muscle reference tissue correlated with tissue PARP-1 expression (P < 0.02, n = 10). The tumor-to-normal muscle ratio from a 5-min frame between 50 and 60 min after injection, a potential static scan protocol, closely corresponded to the distribution volume ratio relative to normal muscle and correlated to PARP-1 expression (P < 0.02, n = 10). Conclusion: This study of PARPi analog 18F-FTT showed that uptake kinetics invivo corresponded to expression of PARP-1 and that 18F-FTT quantitation is influenced by radiometabolites that are increasingly present late after injection. Radiometabolites can be controlled by using optimal image acquisition timing or normal muscle reference tissue modeling in dynamic imaging or a tumor-to-normal muscle ratio. Optimal image timing for tumor-to-normal muscle quantification in humans appears to be between 50 and 60 min after injection. Therefore, a clinically practical static imaging protocol commencing 45-55 min after injection may sufficiently balance 18F-FTT uptake with background clearance and radiometabolite interference for quantitative interpretation of PARP-1 expression invivo.

Stimulated echo acquisition mode (STEAM) diffusion tensor imaging with different diffusion encoding times in the supraspinatus muscle: Test-retest reliability and comparison to spin echo diffusion tensor imaging.

Diffusion tensor imaging (DTI) provides insight into the skeletal muscle microstructure and can be acquired using a stimulated echo acquisition mode (STEAM)-based approach to quantify time-dependent tissue diffusion. This study examined diffusion metrics and signal-to-noise ratio (SNR) in the supraspinatus muscle obtained with a STEAM-DTI sequence with different diffusion encoding times (Δ) and compared them to measures from a spin echo (SE) sequence. Ten healthy subjects (mean age 31.5 ± 4.7years; five females) underwent 3-Tesla STEAM and SE-DTI of the shoulder in three sessions. STEAM was acquired with Δ of 100/200/400/600 ms. The diffusion encoding time in SE scans was 19ms (b = 500s/mm2). Region of interest-based measurement of fractional anisotropy (FA), mean diffusivity (MD), and SNR was performed. Intraclass correlation coefficients (ICCs) were computed to assess test-retest reliability. ANOVA with post-hoc pairwise tests was used to compare measures between different Δ of STEAM as well as STEAM and SE, respectively. FA was significantly higher (FASTEAM: 0.38-0.46 vs. FASE: 0.26) and MD significantly lower (MDSTEAM: 1.20-1.33 vs. MDSE: 1.62×10-3mm2/s) in STEAM compared to SE (p < 0.001, respectively). SNR was significantly higher for SE (72.3 ± 8.7) than for STEAM (p < 0.001). ICCs were excellent for FA in STEAM (≥0.911) and SE (0.960). For MD, ICCs were good for STEAM100ms-600ms (≥0.759) and SE (0.752). STEAM and SE exhibited excellent reliability for FA and good reliability for MD in the supraspinatus muscle. SNR was significantly higher in SE compared to STEAM.

Lumbar localized fat distribution parameters are independent predictors of osteoporotic vertebral compression re-fractures (OVCRFs) following Percutaneous Kyphoplasty (PKP): a retrospective matched case-control study.

To investigate potential risk factors for osteoporotic vertebral compression re-fractures (OVCRFs) following percutaneous kyphoplasty (PKP). Patients who underwent PKP from January 2012 to January 2020 were included in this study within the same institution. Cases were defined as patients who experienced OVCRFs, while controls were matched based on corresponding clinical characteristics from those patients without OVCRFs. The lumbar localized fat distribution parameters, including the fat infiltration ratio (FIR) in muscles [multifidus (MF), erector spinae (ES), paravertebral muscles (PVM), and psoas major (PS)] and subcutaneous fat thickness (SFT), were compared between the two groups through radiological data. And other clinical data that may be relevant were also compared. Independent risk factors for OVCRFs after PKP were identified through a binary logistic regression analysis. A total of 1391 patients who underwent PKP were included in this study. 51 patients were categorized into the re-fracture group, and 102 patients were selected as matched controls from the remaining cohort. There were statistically significant differences between the two groups in metrics including MF-FIR, ES-FIR, PVM-FIR, PS-FIR, bone mineral density (BMD), body-mass index (BMI), SFT, hemoglobin (Hb), albumin (ALB), alkaline phosphatase (ALP), and triglycerides (TG) (P < 0.05). Binary logistic regression analysis demonstrated that PVM-FIR (P = 0.003), SFT (P < 0.001), BMD (P = 0.011), and ALP (P = 0.005) were independent predictors for the occurrence of OVCRFs. This study discovered that lumbar localized fat distribution parameters including PVM-FIR and SFT are independent predictors of OVCRFs. Additionally, BMD and ALP were found to be independent predictors of OVCRFs.

Body Composition and Progression of Biopsy-Proven Non-Alcoholic Fatty Liver Disease in Patients With Obesity.

Obesity is a significant risk factor for the progression of non-alcoholic fatty liver disease (NAFLD). However, a convenient and efficacious non-invasive test for monitoring NAFLD progression in patients with obesity is currently lacking. This study aims to investigate the associations between CT-based body composition and the progression of biopsy-proven NAFLD in patients with obesity. Liver biopsy was conducted in patients with obesity, and the progression of NAFLD was evaluated by the NAFLD activity score (NAS). Body composition was assessed through abdominal computed tomography (CT) scans. A total of 602 patients with an average age of 31.65 (±9.33) years old were included, comprising 217 male patients and 385 female patients. The wall skeletal muscle index (SMI), total SMI, and visceral fat index (VFI) were positively correlated with NAS in both male and female patients. Multivariate regression analysis demonstrated significant associations between high liver steatosis and wall SMI (HR: 1.60, 95% CI: 1.12 to 2.30), total SMI (HR: 1.50, 95% CI: 1.02 to 2.08), VSI (HR: 2.16, 95% CI: 1.48 to 3.14), visceral fat to muscle ratio (HR: 1.51, 95% CI: 1.05 to 2.18), and visceral to subcutaneous fat ratio (HR: 1.51, 95% CI: 1.07 to 2.12). Non-alcoholic steatohepatitis (NASH) was significantly associated with wall SMI (HR: 1.52, 95% CI: 1.06 to 2.19) and VSI (HR: 1.50, 95% CI: 1.03 to 2.17). Liver fibrosis ≥ F2 was significantly associated with psoas muscle index (HR: 0.64, 95% CI: 0.44 to 0.93) and psoas skeletal muscle density (HR: 0.61, 95% CI: 0.41 to 0.89). Our study suggested that certain CT-based body composition indicators, notably high VFI, were significantly associated with the progression of NAFLD in patients with obesity. Great attentions and timely managements should be given to these patients with body composition characteristics associated with the risk of NAFLD progression.

Efficacy of adipose-derived stem cells in preventing peripheral nerve adhesion and promoting nerve regeneration: A laboratory investigation in a rat model

BackgroundNeurolysis alone or administration of anti-adhesion products after neurolysis is performed to treat peripheral nerve adhesion; however, the recovery of nerve function is poor. This study aimed to investigate the efficacy of adipose-derived stem cells (ADSCs) for peripheral nerve adhesion in a rat model. MethodsAs a nerve adhesion procedure, the neural bed was coagulated, and the epineurium of the sciatic nerve was sutured to the coagulated neural bed using nylon. Neurolysis was performed 6 weeks after the nerve adhesion procedure, and saline (control group) or ADSCs (ADSC group) were administered around the nerve where neurolysis was performed. Evaluations were performed 6 weeks after the administration. ResultsThe wet weight ratio of the tibialis anterior muscle and nerve conduction velocity, which are indicators of nerve regeneration, were significantly better, while tensile strength, which is an indicator of the severity of nerve adhesion, was significantly lower in the ADSC group than in the control group. In the nerve, the expression of interleukin-10 and transforming growth factor-β in the nerve was significantly higher and that of tumor necrosis factor-α was significantly lower in the ADSC group than in the control group. Furthermore, significantly fewer M1 macrophages and significantly more M2 macrophages were observed in the ADSC group than in the control group. In the perineural scar, significantly fewer perineural collagen fibers and significantly more vascularization were observed in the ADSC group than in the control group. ConclusionsADSCs prevented peripheral nerve adhesion by reducing perineural scarring and enhancing vascularization. Additionally, ADSCs promoted nerve regeneration by decreasing inflammatory cytokine levels and increasing anti-inflammatory cytokine levels, as ADSCs regulated macrophage polarization from M1 to M2 macrophages. These findings hold promise for using ADSCs to treat nerve adhesion.

Prospective Comparison of FOCUS MUSE and Single-Shot Echo-Planar Imaging for Diffusion-Weighted Imaging in Evaluating Thyroid-Associated Ophthalmopathy.

To prospectively compare single-shot (SS) echo-planar imaging (EPI) and field-of-view optimized and constrained undistorted single-shot multiplexed sensitivity-encoding (FOCUS MUSE) for diffusion-weighted imaging (DWI) in evaluating thyroid-associated ophthalmopathy (TAO). SS EPI and FOCUS MUSE DWIs were obtained from 39 patients with TAO (18 male; mean ± standard deviation: 48.3 ± 13.3 years) and 26 healthy controls (9 male; mean ± standard deviation: 43.0 ± 18.5 years). Two radiologists scored the visual image quality using a 4-point Likert scale. The image quality score, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and apparent diffusion coefficient (ADC) of extraocular muscles (EOMs) were compared between the two DWIs. Differences in the ADC of EOMs were also evaluated. The performance of discriminating active from inactive TAO was assessed using receiver operating characteristic curves. The correlation between ADC and clinical activity score (CAS) was analyzed using Spearman correlation. Compared with SS EPI DWI, FOCUS MUSE DWI demonstrated significantly higher image quality scores (P < 0.001), a higher SNR and CNR on the lateral rectus muscle (LRM) and medial rectus muscle (MRM) (P < 0.05), and a non-significant difference in the ADC of the LRM and MRM. Active TAO showed higher ADC than inactive TAO and healthy controls with both SS EPI and FOCUS MUSE DWIs (P < 0.001). Inactive TAO and healthy controls did not show a significant ADC difference with both DWIs. Compared with SS EPI DWI, FOCUS MUSE DWI demonstrated better discrimination of active from inactive TAO (AUC: 0.925 vs. 0.779; P = 0.007). The ADC was significantly correlated with CAS in SS EPI DWI (r = 0.391, P < 0.001) and FOCUS MUSE DWI (r = 0.645, P < 0.001). FOCUS MUSE DWI provides better images for evaluating EOMs and better performance in diagnosing active TAO than SS EPI DWI. The application of FOCUS MUSE will facilitate the DWI evaluation of TAO.

Dynamic and static nasolabial muscle anatomy of unilateral cleft lip adult patients based on magnetic resonance imaging data.

This study aims to obtain a three-dimensional reconstruction model based on magnetic resonance imaging (MRI) data of patients with different degrees of unilateral cleft lip and analyze the anatomy and changes in multiple groups of nasolabial muscles under dynamic and static conditions. One normal person and four adult patients with unilateral cleft lip were included, and MRI was performed under static (upper and lower lips closed naturally) and dynamic (pout and grin) conditions. 3D Slicer software was used to reconstruct the model and draw the anatomic morphology of nasolabial muscles. The distance between the junction (where the muscle merges into the orbicularis oris) of the levator muscle, zygomaticminor muscle, and zygomatic major muscle to the median sagittal plane, the starting point to the junction point, the dynamic and static junction points, and the angle between the connection of dynamic and static junctions and the horizontal plane were measured under three kinds of movements, and the ratio was calculated. In all patients, under dynamic and static conditions, the distance from the muscle junction to the median sagittal plane, their ratios of the cleft side to the non-cleft side were all greater than 1. While the ratio of the distance from the starting point of the muscle to the junction point is less than 1. At static conditions, the two ratios of the same muscle increased gradiently with the severity of the cleft, and the ratio of the zygomatic minor muscle was prominent in the same patient. The ratio of the cleft side to the non-cleft side was greater than 1, and the value for comparison was the angle of the line from the static to the dynamic junction and the horizontal plane. The symmetry of the insertion site of the orbicularis oris and the linear distance of both sides of the muscle are related to muscle and cleft types. The angle of muscle contraction on the cleft side is greater than that on the non-cleft side.

Fat to muscle ratio as a predictor of survival in young females newly diagnosed with breast cancer

Fat to muscle ratio as a predictor of survival in young females newly diagnosed with breast cancer

Electromyographic comparison of exercises for scapulothoracic muscle activation in men with upper crossed syndrome: A cross-sectional study

ObjectiveThis study aimed to determine the optimal exercise for improving Upper Crossed Syndrome (UCS) using electromyographic (EMG) activity of upper trapezius (UT), middle trapezius (MT), lower trapezius (LT), and serratus anterior (SA) during ten exercises. MethodA cross-sectional study involved 30 male students (mean age: 25.3 ± 2.5 years; height: 176.8 ± 7.2 cm; weight: 77.7 ± 2.5 kg; BMI: 23.8 ± 0.72 kg/m2) with UCS. Participants were selected based on postural assessments (forward head posture ≥44°, rounded shoulder ≥49°, thoracic kyphosis ≥42°). EMG was used to measure activation levels of UT, MT, LT, and SA, and the UT activation ratio relative to MT, LT, and SA during ten exercises. One-way ANOVA was applied for data analysis. ResultsSide-lying external rotation, standing diagonal flexion with Thera-band, and lying prone “V” demonstrated the least UT activity, with the highest MT and LT activation. The standing diagonal flexion with Thera-band elicited the highest SA activity. UT/MT, UT/LT, and UT/SA ratios were less than one in multiple exercises. Significant differences in muscle activation levels and ratios were observed across all exercises (P ≤ 0.05). ConclusionThe findings suggest significant clinical implications for UCS rehabilitation. The identified exercises effectively engage MT and LT while minimizing UT activation, addressing muscular imbalances. Favorable UT/MT, UT/LT, and UT/SA ratios further support these exercises in correcting UCS. These exercises may help counteract the underlying muscular imbalance in UCS by promoting a more balanced activity ratio among the shoulder girdle muscles, potentially improving posture and reducing UCS symptoms.

Fibroblast activation protein inhibitor positron emission tomography imaging in muscles of patients with idiopathic inflammatory myopathy.

Mesenchymal stromal cells in muscles participate in regeneration following muscle injury. This study explored the potential of [18F]fibroblast activation protein inhibitor (FAPI)-42 positron emission tomography (PET) targeting mesenchymal stromal cells to evaluate disease activity of idiopathic inflammatory myopathy (IIM). Patients with IIM (n = 26) were prospectively included and underwent [18F]FAPI-42 PET/CT and whole-body MRI between January 2023 and July 2023. Patients with malignancies were retrospectively included in the control group and only underwent [18F]FAPI-42 PET/CT (n = 28). [18F]FAPI-42 PET/CT images were evaluated using for avid-FAPI uptake and the target-to-background ratio (TBR). Whole-body MRI was evaluated for oedema, fatty infiltration, and atrophy in 42 muscles in the IIM group. The global FAPI- and MRI-derived parameters were calculated for each. . Clinical assessment of disease activity and muscle strength were collected. Patients with IIM had significantly higher global FAPI-avid muscle ratios (0.68 [interquartile range (IQR): 0.45, 0.79] vs 0.06 [IQR: 0, 0.11], p< 0.001) and global muscle TBR (2.26 [IQR: 1.71, 2.75] vs 1.23 [IQR: 1.02, 1.52], p< 0.001) compared with controls. In the IIM group, the median TBR was higher in muscles with oedema than in those without (2.44 [IQR: 1.46, 3.27] vs 1.31 [IQR: 0.95, 1.99], p< 0.001). Global FAPI-avid muscle ratios significantly correlated with global oedema score (r = 0.833), muscle strength (r=-0.649), serum creatine kinase (r = 0.456), and disease activity index (r = 0.495-0.621). Increased [18F]FAPI-42 uptake was associated with muscle oedema in IIM. FAPI-derived parameters correlated with IIM disease activity. [18F]FAPI-42 is a promising PET tracer for evaluating IIM disease activity.

Synthesis and Evaluation of 99mTc(CO)3 Complexes with Ciprofloxacin Dithiocarbamate for Infection Imaging.

Background: The accurate diagnosis of bacterial infections remains a critical challenge in clinical practice. Traditional imaging modalities like computed tomography (CT) and magnetic resonance imaging (MRI) often fail to distinguish bacterial infections from sterile inflammation. Nuclear medicine, such as technetium-99m (99mTc) radiopharmaceuticals, offers a promising alternative due to its ideal characteristics. Methods: This study explores the development of [2 + 1] mixed-ligand 99mTc-labeled ciprofloxacin dithiocarbamate (Cip-DTC) complexes combined with various phosphine ligands, including triphenylphosphine (PPh3), tris(4-methoxyphenyl)phosphine (TMPP), methyl(diphenyl)phosphine (MePPh2), dimethylphenylphosphine (DMPP), and 1,3,5-triaza-7-phosphaadamantane (ADAP). The characterization of 99mTc-complexes was conducted using rhenium analogs as structural models to ensure similar coordination. Results: Stability studies demonstrated the high integrity (97-98%) of the complexes under various conditions, including cysteine and histidine challenges. Lipophilicity studies indicated that complexes with higher logD7.4 values (1.6-2.7) exhibited enhanced tissue penetration and prolonged circulation. Biodistribution studies in Swiss Albino mice with induced infections and aseptic inflammation revealed distinct patterns. Specifically, the complex fac-[99mTc(CO)3(Cip-DTC)(PPh3)] (2') showed high infected/normal muscle ratios (4.62 at 120 min), while the complex fac-[99mTc(CO)3(Cip-DTC)(TMPP)] (3') demonstrated delayed but effective targeting (infected/normal muscle ratio of 3.32 at 120 min). Conclusions: These findings highlight the potential of 99mTc-labeled complexes as effective radiopharmaceuticals for the differential diagnosis of bacterial infections, advancing nuclear medicine diagnostics. Future studies will focus on optimizing molecular weight, lipophilicity, and stability to further enhance the diagnostic specificity and clinical utility of these radiopharmaceuticals.

Impact of upgrading from a 25-cm to a 30-cm z-axis field of view digital PET/CT in a pediatric hospital

BackgroundIncreased positron emission tomography (PET) scanner z-axis coverage provides an opportunity in pediatrics to reduce dose, anesthesia, or repeat scans due to motion.ObjectiveRecently, our digital PET scanner was upgraded from a 25-cm to a 30-cm z-axis coverage. We compare the two systems through National Electrical Manufacturing Association (NEMA) testing and evaluation of paired images from patients scanned on both systems.Materials and methodsNEMA testing and a retrospective review of pediatric patients who underwent clinically indicated 18F-fluorodeoxyglucose (FDG) PET computed tomography (PET/CT) on both systems with unchanged acquisition parameters were performed. Image quality was assessed with liver signal to noise ratio (SNR-liver) and contrast to noise ratio (CNR) in the thigh muscle and liver with results compared with an unpaired t-test. Three readers independently reviewed paired (25 cm and 30 cm) images from the same patient, blinded to scanner configuration.ResultsExpansion to 30 cm increased system sensitivity to 29.8% (23.4 cps/kBq to 30.4 cps/kBq). Seventeen patients (6 male/11 female, median age 12.5 (IQR 8.3–15.0) years, median weight 53.7 (IQR 34.2–68.7) kg) were included. SNR-liver and CNR increased by 35.1% (IQR 19.0–48.4%) and 43.1% (IQR 6.2–50.2%) (P-value <0.001), respectively. All readers preferred images from the 30-cm configuration. A median of 1 (IQR 1–1) for fewer bed positions was required with the 30-cm configuration allowing a median of 91 (IQR 47–136) s for shorter scans.ConclusionIncreasing z-axis coverage from 25 to 30 cm on a current-generation digital PET scanner significantly improved PET system performance and patient image quality, and reduced scan duration.

Efficacy of compressed sensing and deep learning reconstruction for adult female pelvic MRI at 1.5 T

BackgroundWe aimed to determine the capabilities of compressed sensing (CS) and deep learning reconstruction (DLR) with those of conventional parallel imaging (PI) for improving image quality while reducing examination time on female pelvic 1.5-T magnetic resonance imaging (MRI).MethodsFifty-two consecutive female patients with various pelvic diseases underwent MRI with T1- and T2-weighted sequences using CS and PI. All CS data was reconstructed with and without DLR. Signal-to-noise ratio (SNR) of muscle and contrast-to-noise ratio (CNR) between fat tissue and iliac muscle on T1-weighted images (T1WI) and between myometrium and straight muscle on T2-weighted images (T2WI) were determined through region-of-interest measurements. Overall image quality (OIQ) and diagnostic confidence level (DCL) were evaluated on 5-point scales. SNRs and CNRs were compared using Tukey’s test, and qualitative indexes using the Wilcoxon signed-rank test.ResultsSNRs of T1WI and T2WI obtained using CS with DLR were higher than those using CS without DLR or conventional PI (p < 0.010). CNRs of T1WI and T2WI obtained using CS with DLR were higher than those using CS without DLR or conventional PI (p < 0.003). OIQ of T1WI and T2WI obtained using CS with DLR were higher than that using CS without DLR or conventional PI (p < 0.001). DCL of T2WI obtained using CS with DLR was higher than that using conventional PI or CS without DLR (p < 0.001).ConclusionCS with DLR provided better image quality and shorter examination time than those obtainable with PI for female pelvic 1.5-T MRI.Relevance statementCS with DLR can be considered effective for attaining better image quality and shorter examination time for female pelvic MRI at 1.5 T compared with those obtainable with PI.Key PointsPatients underwent MRI with T1- and T2-weighted sequences using CS and PI.All CS data was reconstructed with and without DLR.CS with DLR allowed for examination times significantly shorter than those of PI and provided significantly higher signal- and CNRs, as well as OIQ.Graphical

Factors influencing the therapeutic effect of hyperopic correction on esotropia in patients with partially accommodative esotropia.

To collate data on partially accommodative esotropia (PAET) to better understand this condition's aetiology and to evaluate and predict the therapeutic effect of a hyperopic correction on PAET. Eighty-nine consecutive patients diagnosed with PAET with a spherical equivalent (SE) refractive error >+2.50 D were included in this retrospective review. Clinical characteristics, including gender, age, SE, angle of esodeviation, accommodative convergence/accommodation (AC/A) ratio, near-distance disparity (NDD) and anatomical features of the rectus muscles were compared among different PAET subgroups. Multiple linear regression was used to identify independent factors that influenced the therapeutic effect of a hyperopic correction on esotropia. No significant differences were observed for the angle of esodeviation as a function of age in individuals with PAET. The incidence of SE in PAET participants >9 years old was significantly greater than in those <5 and 6-8 years of age. The therapeutic effect of hyperopic correction on esotropia was positively associated with SE both at distance and near. In addition, the limbus insertion distance (LID) of the lateral rectus (LR) muscle was positively associated with NDD at distance, but negatively associated at near. A greater incidence of hyperopia was observed in older (>9 years old) PAET patients. A hyperopic correction had a greater effect on esotropia in individuals with a higher SE, larger LID of the LR muscle and a smaller NDD.

Fat-free noncontrast whole-heart CMR with fast and power-optimized off-resonant water excitation pulses

BackgroundCardiovascular MRI (CMR) faces challenges due to the interference of bright fat signals in visualizing structures like coronary arteries. Effective fat suppression is crucial, especially when using whole-heart CMR techniques. Conventional methods often fall short due to rapid fat signal recovery, leading to residual fat content hindering visualization. Water-selective off-resonant radiofrequency (RF) pulses have been proposed but come with tradeoffs between pulse duration, which increases scan time, and increased RF energy deposit, which limits their applicability due to specific absorption rate (SAR) constraints. The study introduces a lipid-insensitive binomial off-resonant (LIBOR) RF pulse, which addresses concerns about SAR and scan time, and aims to provide a comprehensive quantitative comparison with published off-resonant RF pulses for CMR at 3T. MethodsA short (1ms) LIBOR pulse, with reduced RF power requirements, was developed and implemented in a free-breathing respiratory-self-navigated 3D radial whole-heart CMR sequence at 3T. A binomial off-resonant rectangular (BORR) pulse with matched duration, as well as previously published lipid-insensitive binomial off-resonant excitation (LIBRE) pulses (1ms and 2.2ms), were implemented and optimized for fat suppression in numerical simulations and validated in volunteers (n=3). Whole-heart CMR was performed in volunteers(n=10) with all four pulses. The signal-to-noise ratio (SNR) of ventricular blood, skeletal muscle, myocardium, and subcutaneous fat and the coronary vessel detection rates and sharpness were compared. ResultsExperimental results validated numerical findings and near homogeneous fat suppression was achieved with all four pulses. Comparing the short RF pulses (1ms), LIBOR reduced the RF power nearly two-fold compared with LIBRE, and three-fold compared with BORR, and LIBOR significantly decreased overall fat SNR from cardiac scans, compared to LIBRE and BORR. The reduction in RF pulse duration (from 2.2ms to 1ms) shortened the whole-heart acquisition from 8.5min to 7min. No significant differences in coronary arteries detection and sharpness were found when comparing all four pulses. ConclusionLIBOR pulses enabled whole-heart CMR under 7minutes at 3T, with large volume fat signal suppression, while reducing RF power compared with LIBRE and BORR pulses. LIBOR is an excellent candidate to address SAR problems encountered in CMR sequences where fat suppression remains challenging and short RF pulses are required. AVAILABILITY OF DATA AND MATERIALSAn online repository containing the anonymized human MRI raw data, as well as RF pulse shapes used in this study is publicly available at:https://zenodo.org/records/8338079(PART 1: KNEE V1-V3, HEART V1-V5)https://zenodo.org/records/10715769 (PART 2: HEART V6-V10)Matlab code to 1) simulate the different RF pulses within a GRE sequence and 2) to read and display the anonymized raw data is available from: https://github.com/QIS-MRI/LIBOR_LIBRE_BORR_SimulationCodeThe compiled research sequence can be requested through the Teamplay platform of Siemens Healthineers.

PMMA-induced biofilm promotes Schwann cells migration and proliferation mediated by EGF/Tnc/FN1 to improve sciatic nerve defect

ObjectiveThe purpose of this study is to investigate the role of PMMA-induced biofilm in nerve regeneration compared with silicone-induced biofilm involved in the mechanism. MethodsPMMA or silicon rods were placed next to the sciatic nerve to induce a biological membrane which was assayed by PCR, Western blot, immunohistochemistry, immunofluorescence and proteomics. A 10 mm sciatic nerve gaps were repaired with the autologous nerve wrapped in an induced biological membrane. The repair effects were observed through general observation, functional evaluation of nerve regeneration, ultrasound examination, neural electrophysiology, the wet weight ratio of bilateral pretibial muscle and histological evaluation. Cell proliferation and migration of Schwann cells co-cultured with EGF-treated fibroblasts combined with siRNA were investigated. ResultsThe results indicated that expression of GDNF, NGF and VEGF along with neovascularization was similar in the silicone and PMMA group and as the highest at 6 weeks after operation. Nerve injury repair mediated by toluidine blue and S100β/NF200 expression, the sensory and motor function evaluation, ultrasound, target organ muscle wet-weight ratio, percentage of collagen fiber, electromyography and histochemical staining were not different between the two groups and better than blank group. EGF-treated fibroblasts promoted proliferation and migration may be Tnc expression dependently. ConclusionOur study suggested that PMMA similar to silicon induced biofilm may promote autogenous nerve transplantation to repair nerve defects through EGF/Tnc/FN1 to increase Schwann cells proliferation and migration.

A thiourea-bridged 99mTc(CO)3-dipicolylamine-2-nitroimidazole complex for targeting tumor hypoxia: Utilizing metabolizable thiourea-bridge to improve pharmacokinetics.

The 2-nitroimidazole based 99mTc-radiopharmaceuticals are widely explored for imaging tumor hypoxia. Radiopharmaceuticals for targeting hypoxia are often lipophilic and therefore, show significant uptake in liver and other vital organs. In this context, lipophilic radiopharmaceuticals with design features enabling faster clearance from liver may be more desirable. A dipicolylamine-NCS bifunctional chelator that could generate a thiourea-bridge up on conjugation to primary amine bearing molecule was used to synthesize a 2-nitroimidazole-dipicolyl amine ligand for radiolabeling with 99mTc(CO)3 core. Corresponding Re(CO)3-analogue was prepared to establish the structure of 2-nitroimidazole-99mTc(CO)3 complex prepared in trace level. The 2-nitroimidazole-99mTc(CO)3 complex showed a hypoxic to normoxic ratio of ~2.5 in CHO cells at 3 h. In vivo, the complex showed accumulation and retention in tumor with high tumor to blood and tumor to muscle ratio. The study demonstrated the utility of metabolizable thiourea-bridge in 2-nitroimidazole-99mTc(CO)3 complex in inducing faster clearance of the radiotracer from liver. The dipicolylamine-NCS bifunctional chelator reported herein can also be used for radiolabeling other class of target specific molecules with 99mTc(CO)3 core.

Blocking TSP1 Ameliorates Diabetes Mellitus-Induced Erectile Dysfunction by Inhibiting the TGF-β/SMAD Pathway.

To examine the role and mechanism of thrombospondin-1 (TSP1) in the development of fibrosis in diabetes mellitus-induced erectile dysfunction (DMED). DMED was induced by intraperitoneal streptozotocin injection. All rats were categorized into three groups: control group (n=8), DMED group (n=8) and DMED+Leu-Ser-Lys-Leu (LSKL) group (n=8). After eight weeks following the induction of diabetes mellitus, the DMED+LSKL group was subjected to intraperitoneal injections of LSKL twice weekly for four weeks. To measure intracavernous pressure (ICP), a 25-gauge needle connected to a PE tube containing heparin was inserted into the corpus cavernosum (CC). Additionally, a needle was inserted into the carotid artery to measure mean arterial pressure (MAP). Sirius red staining and Masson trichrome staining were utilized to assess CC fibrosis. Moreover, high glucose (HG)-induced CC smooth muscle cells (CCSMCs) and CC fibroblasts (CCFs) were treated with or without LSKL. Western blotting and immunofluorescence were utilized to assess the phosphorylation and expression of related proteins. Compared with those in the control group, the ratio of the maximum ICP to the MAP markedly decreased in the DMED group, as did the ratio of smooth muscle to collagen and the ratio of collagen I to collagen III. These ratios were greater in the DMED+LSKL group than in the DMED group. TSP1 was highly expressed in the CC of DMED rats. In vitro experiments indicated that TSP1 expression significantly increased in the medium of CCSMCs and CCFs cultured in HG media and that the TGF-β pathway was activated in CCSMCs. Collagen IV was overexpressed in CCSMCs, indicating severe fibrosis was severe. Adding LSKL or knocking TSP1 down can prevent the activation of TGF-β signaling, as well as the overexpression of collagen IV in CCSMCs promoted by TSP1 secreted from CCSMCs itself or CCFs. TSP1 expression is increased in the CC of DMED rats. HG-induced TSP1 secretion via autocrine signaling from CCSMCs and/or paracrine signaling from CCFs to accelerate penile fibrosis. LSKL, an antagonist of TSP1, could improve erectile dysfunction by inhibiting the TGF-β/SMAD pathway.

O-GlcNAcylation of SERCA protects skeletal muscle in hibernating Spermophilus dauricus from disuse atrophy

Long-term inactivity of skeletal muscle results in muscular disuse atrophy; however, hibernating animals do not experience muscular disuse atrophy during the hibernation period. The molecular mechanism underlining the anti-atrophy effect in these animals is unclear. O-linked N acetyl-β-D-glucosaminylation (O-GlcNAcylation) and its effect on cell signaling pathways are important mechanisms underlying muscular disuse atrophy; thus, in this study, we investigated O-GlcNAcylation changes during hibernation in Spermophilus dauricus to explore the role of O-GlcNAcylation in the muscle disuse atrophy resistance of hibernating animals. The results showed that during hibernation, the muscle fiber cross-sectional area and ratio of muscle fiber did not change, and the morphological structure of the muscle remained intact, with normal contractile function. The level of O-GlcNAcylation decreased during hibernation, but quickly returned to normal in the periodic arousal stage. The O-GlcNAcylation level of sarcoplasmic/endoplasmic reticulum calcium ATPase 1 (SERCA1) decreased, whereas its activity increased. The decrease in O-GlcNAcylation of SERCA could result in the decreased binding of phospholamban to SERCA1, thus decreasing its inhibition to SERCA1 activity. This in turn can inhibit muscle cell calcium overload, maintain muscle cell calcium homeostasis, and stabilize the calpain proteolytic pathway, ultimately inhibiting skeletal muscle atrophy. Our results demonstrate that periodic arousal along with returning O-GlcNAcylation level to normal are important mechanisms in preventing disuse atrophy of skeletal muscle during hibernation.

Characteristics and radiological hazard assessment of 210Po in tilapia (Oreochromis niloticus) in Vietnam.

210Po is one of the most toxic natural radionuclides. This isotope's characteristics and radiological hazard assessment have been concerned in different objects. In this study, the 210Po activities were determined in different tilapia organs/parts of 20 sample groups by alpha spectrometry. The 210Po activities in muscle, bone, intestine organs, and stomach contents unevenly distributed with a wide range from 0.5 ± 0.2 to 2.8 ± 0.4 and 1.4 ± 0.2Bq·kg-1 wet.wt on average, from 0.6 ± 0.3 to 6.3 ± 0.7 and 3.5 ± 0.4Bq·kg-1 wet.wt on average, from 46.3 ± 2.9 to 263 ± 9.7 and 115 ± 6Bq·kg-1 wet.wt on average, and 20.9 ± 1.2 to 800 ± 29 and 197 ± 9Bq·kg-1 wet.wt on average, respectively. The average 210Po activities in different parts of tilapia trend in order of CMuscle < CBone < CIntestine < CStomach contents. Insignificant correlations were observed between 210Po activities in tilapia organs with their total fish mass. The result could depend on feeding types, diet, different nutrient levels, metabolism, and excretion of 210Po in different ages. The concentration ratios (CRs) of tilapia muscle and bone organs were recorded with low values, while it was far greater than the CRs for the intestine organ. Annual committed effective doses contributing from 210Po concentration due to tilapia fish consumption were within the allowable limits for muscle and bone organs, while those values for intestine organs were far higher than the allowable limit value (assuming similar amount consumption of 30kg·year-1 for each organ). The Erica tool was used to estimate the dose and risk to tilapia from 210Po exposure. Based on the calculated results, it can be seen that there was insignificant concern for tilapia due to ionizing radiation in the study area.