Increasing the scan-efficiency of pulmonary imaging at 0.55 T using iterative concomitant field and motion-corrected reconstruction.

PURPOSE: To develop an iterative concomitant field and motion corrected (iCoMoCo) reconstruction for isotropic high-resolution UTE pulmonary imaging at 0.55 T. METHODS: A free-breathing golden-angle stack-of-spirals UTE sequence was used to acquire data for 8 min with prototype and commercial 0.55 T MRI scanners. The data was binned into 12 respiratory phases based on superior-inferior navigator readouts. The previously published iterative motion corrected (iMoCo) reconstruction was extended to include concomitant field correction directly in the cost function. The reconstruction was implemented within the Gadgetron framework for inline reconstruction. Data were retrospectively reconstructed to simulate scan times of 2, 4, 6, and 8 min. Image quality was assessed using apparent SNR and image sharpness. The technique was evaluated in healthy volunteers and patients with known lung pathology including coronavirus disease 2019 infection, chronic granulomatous disease, lymphangioleiomyomatosis, and lung nodules. RESULTS: The technique provided diagnostic-quality images, and image quality was maintained with a slight loss in SNR for simulated scan times down to 4 min. Parenchymal apparent SNR was 4.33 ± 0.57, 5.96 ± 0.65, 7.36 ± 0.64, and 7.87 ± 0.65 using iCoMoCo with scan times of 2, 4, 6, and 8 min, respectively. Image sharpness at the diaphragm was comparable between iCoMoCo and reference images. Concomitant field corrections visibly improved the sharpness of anatomical structures away from the isocenter. Inline image reconstruction and artifact correction were achieved in <5 min. CONCLUSION: The proposed iCoMoCo pulmonary imaging technique can generate diagnostic quality images with 1.75 mm isotropic resolution in less than 5 min using a 6-min acquisition, on a 0.55 T scanner.

Inline automatic quality control of 2D phase-contrast flow MRI for subject-specific scan time adaptation.

PURPOSE: To develop an inline automatic quality control to achieve consistent diagnostic image quality with subject-specific scan time, and to demonstrate this method for 2D phase-contrast flow MRI to reach a predetermined SNR. METHODS: We designed a closed-loop feedback framework between image reconstruction and data acquisition to intermittently check SNR (every 20 s) and automatically stop the acquisition when a target SNR is achieved. A free-breathing 2D pseudo-golden-angle spiral phase-contrast sequence was modified to listen for image-quality messages from the reconstructions. Ten healthy volunteers and 1 patient were imaged at 0.55 T. Target SNR was selected based on retrospective analysis of cardiac output error, and performance of the automatic SNR-driven "stop" was assessed inline. RESULTS: SNR calculation and automated segmentation was feasible within 20 s with inline deployment. The SNR-driven acquisition time was 2 min 39 s ± 67 s (aorta) and 3 min ± 80 s (main pulmonary artery) with a min/max acquisition time of 1 min 43 s/4 min 52 s (aorta) and 1 min 43 s/5 min 50 s (main pulmonary artery) across 6 healthy volunteers, while ensuring a diagnostic measurement with relative absolute error in quantitative flow measurement lower than 2.1% (aorta) and 6.3% (main pulmonary artery). CONCLUSION: The inline quality control enables subject-specific optimized scan times while ensuring consistent diagnostic image quality. The distribution of automated stopping times across the population revealed the value of a subject-specific scan time.

Substratifying the risk of covert malignancy in significant rectal polyps: Outcomes from a specialist multidisciplinary team (MDT).

AIM: A treatment strategy for patients with a significant polyp or early colon cancer (SPECC) of the rectum presents a challenge due to the significant rate of covert malignancy and lack of standardized assessment. For this reason, NICE recommends multidisciplinary meetings to improve outcomes. The primary aim of the present study was to report the performance of our specialist early rectal cancer (SERC) multidisciplinary team (MDT) in correctly substratifying the risk of cancer and to discuss the limitations of staging investigations in those patients with "poor outcomes". METHOD: This was a retrospective review of patients referred to our SERC MDT from 2014 to 2019. Lesions were assigned by the MDT to three pre-resection categories (low, intermediate, high) according to the risk of covert malignancy. Resection method and final histology were compared to the pre-resection categories. RESULTS: Of 350 SPECC lesions, 174 were assessed as low-risk, 108 intermediate-risk and 68 high-risk. The cancer incidence was 4.8%, 8.3% and 53%, respectively (15.5% overall). Eight lesions were categorized as low-risk but following piecemeal resection were found to be malignant. Five lesions, three of which were categorized as high-risk, were ultimately benign following conventional surgery. One pT1sm1 cancer, removed by anterior resection, may have been treated by local excision. CONCLUSION: A total of 83% of malignant polyps were triaged to an en bloc resection technique and surgical resection avoided for nearly all benign lesions. However, 12 patients from this cohort were deemed to have a poor outcome because of miscategorization. Further comparative research is needed to establish the optimum strategy for rectal SPECC lesion assessment. ORIGINALITY STATEMENT: There is currently no consensus for staging significant polyps of the rectum. This paper reports the effectiveness of a specialist early rectal cancer MDT to correctly risk-stratify significant rectal polyps. It underscores the importance of accurate categorization for treatment decision-making, while acknowledging the limitations of current staging modalities.

Dynamic lung water MRI during exercise stress.

PURPOSE: Exercise-induced dyspnea caused by lung water is an early heart failure symptom. Dynamic lung water quantification during exercise is therefore of interest to detect early stage disease. This study developed a time-resolved 3D MRI method to quantify transient lung water dynamics during rest and exercise stress. METHODS: The method was evaluated in 15 healthy subjects and 2 patients with heart failure imaged in transitions between rest and exercise, and in a porcine model of dynamic extravascular lung water accumulation through mitral regurgitation (n = 5). Time-resolved images were acquired at 0.55T using a continuous 3D stack-of-spirals proton density weighted sequence with 3.5 mm isotropic resolution, and derived using a motion corrected sliding-window reconstruction with 90-s temporal resolution in 20-s increments. A supine MRI-compatible pedal ergometer was used for exercise. Global and regional lung water density (LWD) and percent change in LWD (ΔLWD) were automatically quantified. RESULTS: A ΔLWD increase of 3.3 ± 1.5% was achieved in the animals. Healthy subjects developed a ΔLWD of 7.8 ± 5.0% during moderate exercise, peaked at 16 ± 6.8% during vigorous exercise, and remained unchanged over 10 min at rest (-1.4 ± 3.5%, p = 0.18). Regional LWD were higher posteriorly compared the anterior lungs (rest: 33 ± 3.7% vs 20 ± 3.1%, p < 0.0001; peak exercise: 36 ± 5.5% vs 25 ± 4.6%, p < 0.0001). Accumulation rates were slower in patients than healthy subjects (2.0 ± 0.1%/min vs 2.6 ± 0.9%/min, respectively), whereas LWD were similar at rest (28 ± 10% and 28 ± 2.9%) and peak exercise (ΔLWD 17 ± 10% vs 16 ± 6.8%). CONCLUSION: Lung water dynamics can be quantified during exercise using continuous 3D MRI and a sliding-window image reconstruction.

Concomitant field compensation of spiral turbo spin-echo at 0.55 T.

OBJECTIVE: Diagnostic-quality neuroimaging methods are vital for widespread clinical adoption of low field MRI. Spiral imaging is an efficient acquisition method that can mitigate the reduced signal-to-noise ratio at lower field strengths. As concomitant field artifacts are worse at lower field, we propose a generalizable quadratic gradient-field nulling as an echo-to-echo compensation and apply it to spiral TSE at 0.55 T. MATERIALS AND METHODS: A spiral in-out TSE acquisition was developed with a compensation for concomitant field variation between spiral interleaves, by adding bipolar gradients around each readout to minimize phase differences at each refocusing pulse. Simulations were performed to characterize concomitant field compensation approaches. We demonstrate our proposed compensation method in phantoms and (n = 8) healthy volunteers at 0.55 T. RESULTS: Spiral read-outs with integrated spoiling demonstrated strong concomitant field artifacts but were mitigated using the echo-to-echo compensation. Simulations predicted a decrease of concomitant field phase RMSE between echoes of 42% using the proposed compensation. Spiral TSE improved SNR by 17.2 ± 2.3% compared to reference Cartesian acquisition. DISCUSSION: We demonstrated a generalizable approach to mitigate concomitant field artifacts for spiral TSE acquisitions via the addition of quadratic-nulling gradients, which can potentially improve neuroimaging at low-field through increased acquisition efficiency.

Tyrosinase inhibitory activity of Sargassum fusiforme and characterisation of bioactive compounds.

INTRODUCTION: Sargassum fusiforme (Harvey) Setchell, also known as Tot (in Korean) and Hijiki (in Japanese), is widely consumed in Korea, Japan, and China due to its health promoting properties. However, the bioactive component behind the biological activity is still unknown. OBJECTIVES: We aimed to optimise the extraction conditions for achieving maximum tyrosinase inhibition activity by using two sophisticated statistical tools, that is, response surface methodology (RSM) and artificial neural network (ANN). Moreover, high-resolution mass spectrometry (HRMS) was used to tentatively identify the components, which are then further studied for molecular docking study using 2Y9X protein. METHODOLOGY: RSM central composite design was used to conduct extraction using microwave equipment, which was then compared to ANN. Electrospray ionisation tandem mass spectrometry (ESI-MS/MS) was used to tentatively identify bioactive components, which were then docked to the 2Y9X protein using AutoDock Vina and MolDock software. RESULTS: Maximum tyrosinase inhibition activity of 79.530% was achieved under optimised conditions of time: 3.27 min, temperature: 128.885°C, ethanol concentration: 42.13%, and microwave intensity: 577.84 W. Furthermore, 48 bioactive compounds were tentatively identified in optimised Sargassum fusiforme (OSF) extract, and among them, seven phenolics, five flavonoids, five lignans, six terpenes, and five sulfolipids and phospholipids were putatively reported for the first time in Sargassum fusiforme. Among 48 bioactive components, trifuhalol-A, diphlorethohydroxycarmalol, glycyrrhizin, and arctigenin exhibited higher binding energies for 2Y9X. CONCLUSION: Taken together, these findings suggest that OSF extract can be used as an effective skin-whitening source on a commercial level and could be used in topical formulations by replacing conventional drugs.

Association of heavy metals and trace elements in carcinoma urinary bladder: A case-controlled study.

Introduction: Abnormal levels of heavy metals (HM) and trace elements (TE) affect body metabolism and can induce carcinogenesis. This study aims to evaluate the role of HM and TE in carcinoma urinary bladder (CAUB). Methods: Patients with biopsy-proven CAUB (n = 100) were taken as the study group, while age-and sex-matched healthy volunteers were taken as control (n = 100). Blood and urine samples were compared for Arsenic (As), Copper (Cu), Manganese (Mn), Selenium (Se), Cadmium (Cd), Lead (Pb), and Mercury (Hg) levels. Serum glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and lipid peroxidation (LPO) levels were assessed to know the redox status between the two groups. Results: A significantly higher blood level of As, Mn, and Pb was observed in CAUB cases as compared to controls. Blood Se level was significantly lower in CAUB patients. On comparing urinary levels, CAUB patients had a higher As, Mn, and Pb levels compared to controls. Further, 68% and 59% of patients had their blood and urinary HM and TE levels above the permitted level, respectively. CAUB cases also had a lower GSH-Px (113.5 ± 44.7 vs. 163.9 ± 120.5, P = 0.0002), lower SOD levels (11.35 ± 5.6 vs. 13.75 ± 3.9, P = 0.008), and a higher LPO levels (15.5 ± 14.7 vs. 11.18 ± 11.2, P = 0.02) in the serum. Conclusions: A significantly higher concentration of As, Mn, and Pb was noted in the blood and urine of CAUB patients compared to controls. CAUB cases also had lower serum GSH-Px and SOD levels with a concomitant increased serum LPO assay suggesting underlying oxidative stress.

Self-gated 3D stack-of-spirals UTE pulmonary imaging at 0.55T.

PURPOSE: To develop an isotropic high-resolution stack-of-spirals UTE sequence for pulmonary imaging at 0.55 Tesla by leveraging a combination of robust respiratory-binning, trajectory correction, and concomitant-field corrections. METHODS: A stack-of-spirals golden-angle UTE sequence was used to continuously acquire data for 15.5 minutes. The data was binned to a stable respiratory phase based on superoinferior readout self-navigator signals. Corrections for trajectory errors and concomitant field artifacts, along with image reconstruction with conjugate gradient SENSE, were performed inline within the Gadgetron framework. Finally, data were retrospectively reconstructed to simulate scan times of 5, 8.5, and 12 minutes. Image quality was assessed using signal-to-noise, image sharpness, and qualitative reader scores. The technique was evaluated in healthy volunteers, patients with coronavirus disease 2019 infection, and patients with lung nodules. RESULTS: The technique provided diagnostic quality images with parenchymal lung SNR of 3.18 ± 0.0.60, 4.57 ± 0.87, 5.45 ± 1.02, and 5.89 ± 1.28 for scan times of 5, 8.5, 12, and 15.5 minutes, respectively. The respiratory binning technique resulted in significantly sharper images (p < 0.001) as measured with relative maximum derivative at the diaphragm. Concomitant field corrections visibly improved sharpness of anatomical structures away from iso-center. The image quality was maintained with a slight loss in SNR for simulated scan times down to 8.5 minutes. Inline image reconstruction and artifact correction were achieved in <5 minutes. CONCLUSION: The proposed pulmonary imaging technique combined efficient stack-of-spirals imaging with robust respiratory binning, concomitant field correction, and trajectory correction to generate diagnostic quality images with 1.75 mm isotropic resolution in 8.5 minutes on a high-performance 0.55 Tesla system.

Myocardial blood flow is the dominant factor influencing cardiac magnetic resonance adenosine stress T2.

Stress imaging identifies ischemic myocardium by comparing hemodynamics during rest and hyperemic stress. Hyperemia affects multiple hemodynamic parameters in myocardium, including myocardial blood flow (MBF), myocardial blood volume (MBV), and venous blood oxygen levels (PvO2 ). Cardiac T2 is sensitive to these changes and therefore is a promising non-contrast option for stress imaging; however, the impact of individual hemodynamic factors on T2 is poorly understood, making the connection from altered T2 to changes within the tissue difficult. To better understand this interplay, we performed T2 mapping and measured various hemodynamic factors independently in healthy pigs at multiple levels of hyperemic stress, induced by different doses of adenosine (0.14-0.56 mg/kg/min). T1 mapping quantified changes in MBV. MBF was assessed with microspheres, and oxygen consumption was determined by the rate pressure product (RPP). Simulations were also run to better characterize individual contributions to T2. Myocardial T2, MBF, oxygen consumption, and MBV all changed to varying extents between each level of adenosine stress (T2 = 37.6-41.8 ms; MBF = 0.48-1.32 mL/min/g; RPP = 6507-4001 bmp*mmHg; maximum percent change in MBV = 1.31%). Multivariable analyses revealed MBF as the dominant influence on T2 during hyperemia (significant ß-values >7). Myocardial oxygen consumption had almost no effect on T2 (ß-values <0.002); since PvO2 is influenced by both oxygen consumption and MBF, PvO2 changes detected by T2 during adenosine stress can be attributed to MBF. Simulations varying PvO2 and MBV confirmed that PvO2 had the strongest influence on T2, but MBV became important at high PvO2 . Together, these data suggest a model where, during adenosine stress, myocardial T2 responds predominantly to changes in MBF, but at high hyperemia MBV is also influential. Thus, changes in adenosine stress T2 can now be interpreted in terms of the physiological changes that led to it, enabling T2 mapping to become a viable non-contrast option to detect ischemic myocardial tissue.

Imaging gravity-induced lung water redistribution with automated inline processing at 0.55 T cardiovascular magnetic resonance.

BACKGROUND: Quantitative assessment of dynamic lung water accumulation is of interest to unmask latent heart failure. We develop and validate a free-breathing 3D ultrashort echo time (UTE) sequence with automated inline image processing to image changes in lung water density (LWD) using high-performance 0.55 T cardiovascular magnetic resonance (CMR). METHODS: Quantitative lung water CMR was performed on 15 healthy subjects using free-breathing 3D stack-of-spirals proton density weighted UTE at 0.55 T. Inline image reconstruction and automated image processing was performed using the Gadgetron framework. A gravity-induced redistribution of LWD was provoked by sequentially acquiring images in the supine, prone, and again supine position. Quantitative validation was performed in a phantom array of vials containing mixtures of water and deuterium oxide. RESULTS: The phantom experiment validated the capability of the sequence in quantifying water density (bias ± SD 4.3 ± 4.8%, intraclass correlation coefficient, ICC = 0.97). The average global LWD was comparable between imaging positions (supine 24.7 ± 3.4%, prone 22.7 ± 3.1%, second supine 25.3 ± 3.6%), with small differences between imaging phases (first supine vs prone 2.0%, p < 0.001; first supine vs second supine - 0.6%, p = 0.001; prone vs second supine - 2.7%, p < 0.001). In vivo test-retest repeatability in LWD was excellent (- 0.17 ± 0.91%, ICC = 0.97). A regional LWD redistribution was observed in all subjects when repositioning, with a predominant posterior LWD accumulation when supine, and anterior accumulation when prone (difference in anterior-posterior LWD: supine - 11.6 ± 2.7%, prone 5.5 ± 2.7%, second supine - 11.4 ± 2.9%). Global LWD maps were calculated inline within 23.2 ± 0.3 s following the image reconstruction using the automated pipeline. CONCLUSIONS: Redistribution of LWD due to gravitational forces can be depicted and quantified using a validated free-breathing 3D proton density weighted UTE sequence and inline automated image processing pipeline on a high-performance 0.55 T CMR system.

Robust autocalibrated structured low-rank EPI ghost correction.

PURPOSE: We propose and evaluate a new structured low-rank method for echo-planar imaging (EPI) ghost correction called Robust Autocalibrated LORAKS (RAC-LORAKS). The method can be used to suppress EPI ghosts arising from the differences between different readout gradient polarities and/or the differences between different shots. It does not require conventional EPI navigator signals, and is robust to imperfect autocalibration data. METHODS: Autocalibrated LORAKS is a previous structured low-rank method for EPI ghost correction that uses GRAPPA-type autocalibration data to enable high-quality ghost correction. This method works well when the autocalibration data are pristine, but performance degrades substantially when the autocalibration information is imperfect. RAC-LORAKS generalizes Autocalibrated LORAKS in two ways. First, it does not completely trust the information from autocalibration data, and instead considers the autocalibration and EPI data simultaneously when estimating low-rank matrix structure. Second, it uses complementary information from the autocalibration data to improve EPI reconstruction in a multi-contrast joint reconstruction framework. RAC-LORAKS is evaluated using simulations and in vivo data, including comparisons to state-of-the-art methods. RESULTS: RAC-LORAKS is demonstrated to have good ghost elimination performance compared to state-of-the-art methods in several complicated EPI acquisition scenarios (including gradient-echo brain imaging, diffusion-encoded brain imaging, and cardiac imaging). CONCLUSIONS: RAC-LORAKS provides effective suppression of EPI ghosts and is robust to imperfect autocalibration data.

Oxygen-enhanced functional lung imaging using a contemporary 0.55 T MRI system.

The purpose of this study was to evaluate oxygen-enhanced pulmonary imaging at 0.55 T with 3D stack-of-spirals ultrashort-TE (UTE) acquisition. Oxygen-enhanced pulmonary MRI offers the measurement of regional lung ventilation and perfusion using inhaled oxygen as a contrast agent. Low-field MRI systems equipped with contemporary hardware can provide high-quality structural lung imaging by virtue of the prolonged T2 *. Fortuitously, the T1 relaxivity of oxygen increases at lower field strengths, which is expected to improve the sensitivity of oxygen-enhanced lung MRI. We implemented a breath-held T1 -weighted 3D stack-of-spirals UTE acquisition with a 7 ms spiral-out readout. Measurement repeatability was assessed using five repetitions of oxygen-enhanced lung imaging in healthy volunteers (n = 7). The signal intensity at both normoxia and hyperoxia was strongly dependent on lung tissue density modulated by breath-hold volume during the five repetitions. A voxel-wise correction for lung tissue density improved the repeatability of percent signal enhancement maps (coefficient of variation = 34 ± 16%). Percent signal enhancement maps were compared in 15 healthy volunteers and 10 patients with lymphangioleiomyomatosis (LAM), a rare cystic disease known to reduce pulmonary function. We measured a mean percent signal enhancement of 9.0 ± 3.5% at 0.55 T in healthy volunteers, and reduced signal enhancement in patients with LAM (5.4 ± 4.8%, p = 0.02). The heterogeneity, estimated by the percent of lung volume exhibiting low enhancement, was significantly increased in patients with LAM compared with healthy volunteers (11.1 ± 6.0% versus 30.5 ± 13.1%, p = 0.01), illustrating the capability to measure regional functional deficits.

Effects of motivational interviewing with conventional physical therapy on rehabilitation of chronic musculoskeletal disorders: A quasi-experimental study.

OBJECTIVE: To compare the effects of motivational interviewing with conventional physical therapy in the rehabilitation of chronic musculoskeletal disorders compared to conventional physical therapy alone. METHODS: The quasi-experimental study was conducted from September 2017 to March 2018 after approval from the University of Health Sciences, Lahore, Pakistan, and comprised patients with chronic musculoskeletal disorders enrolled from various outpatient physical therapy clinics in Lahore. The subjects were alternatively allocated to intervention group A and control group B, with the former receiving motivational interviewing along with conventional physical therapy, and the latter receiving conventional physical therapy alone. The effects of the intervention were measured using visual analogue scale, patient-specific functional scale and exercise compliance chart with two-week follow-up. Data was analysed using SPSS 21. RESULTS: Of the 96 subjects, there were 48(50%) in each of the two groups. There were 21(44%) males and 27(56%) females in group A with a mean age of 50.10±10.35 years, and 23(48%) males and 25(52%) females in group B with a mean age of 50.18±11.58 years. Pain score and functional status were significantly better in group A compared to group B from the baseline to day 14 (p<0.001). Exercise compliance was significantly different between the groups (p<0.001). Intra-group effects of pain intensity, functional status and exercise compliance were also significant (p<0.001). CONCLUSION: Integration of motivational interviewing with conventional physical therapy was found to decrease pain and functional limitations and improve exercise compliance.

Single-shot EPI for ASL-CMR.

PURPOSE: To evaluate single-shot echo planar imaging (SS-EPI), as an alternative to snapshot balanced steady state free precession (bSSFP) imaging, for arterial-spin-labeled cardiac MR (ASL-CMR). This study presents a practical implementation SS-EPI tailored to the needs of ASL-CMR at 3T and demonstrates sequential multi-slice ASL with no increase in scan time. METHODS: Reduced field of view SS-EPI was performed using a 2DRF pulse. A spin-echo was used with crushers optimized to maximize blood suppression and minimize myocardial signal loss, based on experiments in 4 healthy volunteers. SS-EPI was evaluated against the widely used bSSFP reference method in single-slice ASL-CMR in 4 healthy volunteers, during both systole and diastole. Sequential multi-slice ASL-CMR with SS-EPI was demonstrated during diastole (3 slices: basal, mid, and apical short-axis) and during systole (2 slices: mid and apical short-axis), in 3 volunteers. RESULTS: Global myocardial perfusion for diastolic SS-EPI (1.66 ± 0.73 mL/g/min) and systolic SS-EPI (1.50 ± 0.36 mL/g/min) were found to be statistically equivalent (2 one-sided test with a difference of 0.4 mL/g/min) to diastolic bSSFP (duration of 1 cardiac cycle, 1.60 ± 0.80 mL/g/min) with P-values of 0.022 and 0.031, respectively. Global myocardial perfusion for sequential multi-slice experiments was 1.64 ± 0.47, 1.34 ± 0.29, and 1.88 ± 0.58 for basal, mid, and apical SAX slices during diastole and was 1.61 ± 0.35, and 1.66 ± 0.49 for mid and apical slice during systole. These values are comparable to published ASL-CMR and positron emission tomography studies. CONCLUSION: SS-EPI is a promising alternative to bSSFP imaging for ASL-CMR and can potentially improve the spatial coverage of ASL-CMR by 3-fold during diastole and 2-fold during systole, without increasing scan time.

Improved velocity-selective labeling pulses for myocardial ASL.

PURPOSE: To develop and evaluate an improved velocity-selective (VS) labeling pulse for myocardial arterial spin labeling (ASL) perfusion imaging that addresses two limitations of current pulses: (1) spurious labeling of moving myocardium and (2) low labeling efficiency. METHODS: The proposed myocardial VSASL labeling pulse is designed using a Fourier Transform based Velocity-Selective labeling pulse train. The pulse utilizes bipolar velocity-encoding gradients, a 9-tap velocity-encoding envelope, and double-refocusing pulses with Malcolm Levitt phase cycling. Amplitudes of the velocity-encoding envelope were optimized to minimize the labeling of myocardial velocities during stable diastole (±2-3 cm/s) and maximize the labeling of coronary velocities (10-130 cm/s during rest/stress or 10-70 cm/s during rest). Myocardial ASL experiments were performed in seven healthy subjects using the previously developed VS-ASL protocol by Jao et al with the two proposed VS pulses and original VS pulse. Myocardial ASL experiments were also performed using FAIR ASL. Myocardial perfusion and physiological noise (PN) were evaluated and compared. RESULTS: Bloch simulations of the first and second proposed pulses show <2% labeling over ±3 cm/s and ±2 cm/s, respectively. Bloch simulations also show the mean labeling efficiency of arterial blood is 1.23 over the relevant coronary arterial ranges. In-vivo VSASL experiments show the proposed pulses provided comparable measurements to FAIR ASL and reduced TSNR in 5 of 7 subjects compared to the original VS pulse. CONCLUSION: We demonstrate an improved VS labeling pulse specifically for myocardial ASL perfusion imaging to reduce spurious labeling of moving myocardium and PN.

Numerical approximation to the general kinetic model for ASL quantification.

PURPOSE: To develop a numerical approximation to the general kinetic model for arterial spin labeling (ASL) quantification that will enable greater flexibility in ASL acquisition methods. THEORY: The Bloch-McConnell equations are extended to include the effects of single-compartment inflow and outflow on both the transverse and longitudinal magnetization. These can be solved using an extension of Jaynes' matrix formalism with piecewise constant approximation of incoming labeled arterial flow and a clearance operator for outgoing venous flow. METHODS: The proposed numerical approximation is compared with the general kinetic model using simulations of pulsed labeling and pseudo-continuous labeling and a broad range of transit time and bolus duration for tissue blood flow of 0.6 mL/g/min. Accuracy of the approximation is studied as a function of the timestep using Monte-Carlo simulations. Three additional scenarios are demonstrated: (1) steady-pulsed ASL, (2) MR fingerprinting ASL, and (3) balanced SSFP and spoiled gradient-echo sequences. RESULTS: The proposed approximation was found to be arbitrarily accurate for pulsed labeling and pseudo-continuous labeling. The pulsed labeling/pseudo-continuous labeling approximation error compared with the general kinetic model was less than 0.002% (<0.002%) and less than 0.05% (<0.05%) for timesteps of 3 ms and 35 ms, respectively. The proposed approximation matched well with customized signal expressions of steady-pulsed ASL and MR fingerprinting ASL. The simulations of simultaneous modeling of flow, T2 , and magnetization transfer showed an increase in steady-state balanced SSFP and spoiled gradient signals. CONCLUSION: We demonstrate a numerical approximation of the "Bloch-McConnell flow" equations that enables arbitrarily accurate modeling of pulsed ASL and pseudo-continuous labeling signals comparable to the general kinetic model. This enables increased flexibility in the experiment design for quantitative ASL.

Feasibility of coronary endothelial function assessment using arterial spin labeled CMR.

Coronary endothelial dysfunction (CED) is an independent predictor of cardiovascular disease, but its assessment has been limited to invasive coronary angiography. Myocardial perfusion imaging using arterial spin labeled (ASL) cardiac magnetic resonance (CMR) may be an effective non-invasive alternative for detection of CED. Thirty-four patients were recruited: 10 healthy volunteers, 13 at high-risk for coronary artery disease (CAD), and 11 with established CAD. ASL-CMR was performed continuously in a single mid-short axis slice during rest, stress, and recovery. Stress was induced with sustained isometric handgrip exercise, an endothelial dependent stressor. Myocardial perfusion (MP) during rest, peak stress, and recovery were calculated and compared. After excluding subjects unable to complete the protocol or who exhibited poor data quality, 6 healthy, 10 high-risk, and 7 CAD patients were included in the analysis. Average MP (ml/g/min) was 1.31 ± 1.23, 1.61 ± 1.12, and 1.40 ± 0.97 at rest, and 1.64 ± 1.49, 2.31 ± 1.61, and 2.84 ± 1.77 during stress, for the CAD, high-risk and healthy group, respectively. The average MP response (MPstress - MPrest , ml/g/min) was 0.32 ± 1.93, 0.69 ± 1.34, and 1.44 ± 1.46 for CAD, high-risk and healthy group, respectively. MP during handgrip stress was significantly lower for both the CAD (p = 0.0005) and high-risk groups (p = 0.05) compared to the healthy volunteers. In only the healthy subjects, MP was significantly higher in stress compared to rest (p = 0.0002). Participants with CAD had significantly lower MP response compared to healthy volunteers, as detected by ASL-CMR. These findings support the feasibility of ASL-CMR for non-invasive assessment of CED.

RSM- and ANN-Based Multifrequency Ultrasonic Extraction of Polyphenol-Rich Sargassum horneri Extracts Exerting Antioxidative Activity via the Regulation of MAPK/Nrf2/HO-1 Machinery.

Sargassum horneri (SH) is widely consumed as a healthy seaweed food in the Asia-Pacific region. However, the bioactive components contributing to its biological activity remain unknown. Herein, we optimized multifrequency ultrasonic-assisted extraction conditions to achieve higher antioxidant activity using a response surface methodology and an artificial neural network. High-resolution mass spectrometry (HRMS; negative mode) was used to tentatively identify the secondary metabolites in the optimized SH extract, which were further tested against oxidative stress in RAW264.7 cells. Additionally, the identified compounds were analyzed in silico to determine their binding energies with the Keap1 protein (4L7B). We identified 89 compounds using HRMS, among which 19 metabolites (8 polyphenolics, 2 flavonoids, 2 lignans, 2 terpenes, 2 tannins, 2 sulfolipids, and 1 phospholipid) were putatively reported for the first time in SH. The in vitro results revealed that optimized SH extract inhibited oxidative stress via the Nrf2/MAPKs/HO-1 pathway in a dose-dependent manner. This result was validated by performing in silico simulation, indicating that sargaquinoic acid and glycitein-7-O-glucuronide had the highest binding energies (-9.20 and -9.52 Kcal/mol, respectively) toward Keap1 (4L7B). This study offers a unique approach for the scientific community to identify potential bioactive compounds by optimizing the multivariant extraction processing conditions, which could be used to develop functional and nutraceutical foods.

Glycoprotein from Sargassum fusiforme exhibiting anti-inflammatory responses in vitro and in vivo via modulation of TLR4/MyD88 and NF-κB signaling.

This study focuses on the identification and characterization of a glycoprotein from Sargassum fusiforme (Harvey) Setchell (SFGP), as well as investigating its potential anti-inflammatory properties both in vitro and in vivo, along with the underlying mechanism. SDS-PAGE analysis revealed a prominent band with a molecular weight of <10 kDa, consisting of 58.39 % protein and 41.61 % carbohydrates, which was confirmed through glycoprotein staining and Coomassie blue staining. Various analytical techniques, including high-resolution mass spectrometry (HRMS), FTIR, amino acid analysis, and UV-visible spectrometry, provided evidence for the presence of monosaccharides (such as d-glucose and mannose) and 17 amino acids linked by an O-glycopeptide bond. In vitro and in vivo studies were conducted to assess the anti-inflammatory activities of SFGP. The results demonstrated that SFGP effectively attenuated nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expressions in LPS-treated RAW264.7 cells. Moreover, SFGP administration significantly and dose-dependently suppressed TLR4/MyD88 signaling as well as the phosphorylation of MAPKs, IκB, and NF-κB, leading to a reduction in the production of TNF-α, IL-1ß, and IL-6 in LPS-stimulated RAW264.7 cells. Furthermore, the anti-inflammatory efficacy of SFGP was validated in a carrageenan-induced inflammatory mouse model. These findings indicate that SFGP exhibits anti-inflammatory characteristics and has the potential to be utilized as a novel anti-inflammatory agent.