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Purpose: Cerebral venous oxygenation (Yv) is an important physiological parameter and has potential clinical application in many brain diseases. T2‐relaxation‐under‐spin‐tagging (TRUST) is a commonly used MRI method to measure Yv. Harmonization of this technique across MRI vendors is important for dissemination and multicenter studies of brain oxygenation and metabolism as a disease biomarker. Methods: TRUST pulse sequence components and imaging parameters were carefully matched between two major MRI vendors, Philips and Siemens. Each subject (N = 10) was scanned on both scanners within a 2.5‐h period. On each scanner, the subject was scanned in two sessions to assess intersession reproducibility. A hyperoxia challenge was also included in both sessions and on both scanners to evaluate the sensitivity of the technique to Yv changes. Measured Yv values, confidence interval of Yv estimates ( ε Y v), as well as intrasession and intersession coefficient of variation (CoV) of Yv, were compared between the two scanners. Results: Yv measured on the two vendors were highly compatible and strongly correlated (R2 = 0.957). Yv changes associated with hyperoxia challenge were significant on both scanners (P < 0.001) and were also correlated across scanners (P = 0.007). Intrasession and intersession CoV of measured Yv were less than 3% and showed no difference between scanners. ε Y v were less than 1% on both scanners and showed no difference between scanners when echo times were matched on the two scanners. Conclusion: This work suggests that harmonized TRUST MRI can yield highly compatible Yv measurements across different vendors. Magn Reson Med 80:1125–1131, 2018. © 2018 International Society for Magnetic Resonance in Medicine. [ABSTRACT FROM AUTHOR]

Purpose: To develop a non–contrast‐agent MRI technique to quantify cerebral venous T2 in mice. Methods: We implemented and optimized a T2‐relaxation‐under‐spin‐tagging (TRUST) sequence on an 11.7 Tesla animal imaging system. A flow‐sensitive‐alternating‐inversion‐recovery (FAIR) module was used to generate control and label images, pair‐wise subtraction of which yielded blood signals. Then, a T2‐preparation module was applied to produce T2‐weighted images, from which blood T2 was quantified. We conducted a series of technical studies to optimize the imaging slice position, inversion slab thickness, post‐labeling delay (PLD), and repetition time. We also performed three physiological studies to examine the venous T2 dependence on hyperoxia (N = 4), anesthesia (N = 3), and brain aging (N = 5). Results: Our technical studies suggested that, for efficient data acquisition with minimal bias in estimated T2, a preferred TRUST protocol was to place the imaging slice at the confluence of sagittal sinuses with an inversion‐slab thickness of 2.5‐mm, a PLD of 1000 ms and a repetition time of 3.5 s. Venous T2 values under normoxia and hyperoxia (inhaling pure oxygen) were 26.9 ± 1.7 and 32.3 ± 2.2 ms, respectively. Moreover, standard isoflurane anesthesia resulted in a higher venous T2 compared with dexmedetomidine anesthesia (N = 3; P = 0.01) which is more commonly used in animal functional MRI studies to preserve brain function. Venous T2 exhibited a decrease with age (N = 5; P < 0.001). Conclusion: We have developed and optimized a noninvasive method to quantify cerebral venous blood T2 in mouse at 11.7 T. This method may prove useful in studies of brain physiology and pathophysiology in animal models. Magn Reson Med 80:521–528, 2018. © 2017 International Society for Magnetic Resonance in Medicine. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the venous oxygenation and flow in the brain, and determine how they might change under challenged states.Materials and Methods: Eight healthy human subjects (24-37 years) were studied. T2 -relaxation under spin tagging (TRUST) magnetic resonance imaging (MRI) and phase-contrast MRI were performed to measure venous oxygenation and venous blood flow, respectively, in the superior sagittal sinus (SSS), the straight sinus (SS), and the internal jugular veins (IJVs). Venous oxygenation was assessed at room air (0.03%CO2 , 21%O2 ) and under hyperoxia (O%CO2 , 95%O2 , and 5%N2 ) conditions. Venous blood flow was assessed at room air and under hypercapnia (5%CO2 , 21%O2 , and 74%N2 ) conditions. Whole-brain blood flow was also measured at the four feeding arteries of the brain using phase-contrast MRI. The changes in venous oxygenation and blood flow from room air to hyperoxia or hypercapnia conditions were tested using paired t-tests.Results: Venous oxygenation in the SSS, the SS, and the IJVs was 61 ± 4%, 64 ± 4%, and 62 ± 4%, respectively, at room air, and increased to 70 ± 3% (P < 0.01 compared to room air), 71 ± 5% (P = 0.59), and 68 ± 5% (P < 0.05) under hyperoxic condition. The SSS, SS, and IJV drained 46 ± 9%, 16 ± 4%, and 79 ± 1% of whole-brain blood flow, respectively, and this flow distribution did not change under hypercapnic condition (P > 0.5).Conclusion: The results found in this study provide insight into the venous oxygenation and venous flow distribution and its heterogeneity among different venous structures.Level Of Evidence: 1 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2018;47:1091-1098. [ABSTRACT FROM AUTHOR]

Purpose Assessment of brain hemodynamics without exogenous contrast agents is of increasing importance in clinical applications. This study aims to develop an MR perfusion technique that can provide noncontrast and multiparametric estimation of hemodynamic markers. Methods We devised an arterial spin labeling (ASL) method based on the principle of MR fingerprinting (MRF), referred to as MRF-ASL. By taking advantage of the rich information contained in MRF sequence, up to seven hemodynamic parameters can be estimated concomitantly. Feasibility demonstration, flip angle optimization, comparison with Look-Locker ASL, reproducibility test, sensitivity to hypercapnia challenge, and initial clinical application in an intracranial steno-occlusive process, Moyamoya disease, were performed to evaluate this technique. Results Magnetic resonance fingerprinting ASL provided estimation of up to seven parameters, including [ABSTRACT FROM AUTHOR]

Purpose To develop a fast protocol for measuring T1 values in the internal carotid artery (ICA), to validate this technique with in vitro measurements, and to evaluate its reproducibility. Methods A modified Look-Locker sequence was optimized to enable rapid determination of T1 in the ICA at 3T. T1 values from the ICA were compared with in vitro measurements on individually sampled venous blood oxygenated to arterial levels. A test-retest reproducibility study was also conducted. Results The group-averaged arterial blood T1 value was 1908 ± 77 ms for six women (hematocrit = 0.39 ± 0.03) and 1785 ± 55 ms for seven men (hematocrit = 0.45 ± 0.02), which is 100-200 ms longer than the widely adopted value obtained from bovine blood experiments. The arterial T1 value per subject correlated significantly with individual hematocrit values. The intrasession and intersession coefficients of variation were 1.1% and 2.1%, respectively, indicating good precision and reproducibility of our method. Reasonable agreement was observed between the in vivo and in vitro results with a correlation coefficient of 0.78. Conclusion The proposed method can provide fast arterial T1 measurement on individual subjects. When not performing such a subject-specific measurement, we recommend the use of 1908 ms and 1785 ms for healthy women and men, respectively, or 1841 ms for adults in general. Magn Reson Med 77:2296-2302, 2017. © 2016 International Society for Magnetic Resonance in Medicine [ABSTRACT FROM AUTHOR]

The human brain develops rapidly during 32-45 postmenstrual weeks (PMW), a critical stage characterized by dramatic increases of metabolic demand. The increasing metabolic demand can be inferred through measurements of regional cerebral blood flow (CBF), which might be coupled to regional metabolism in preterm brains. Arterial spin labeled (ASL) perfusion MRI is one of the few viable approaches for imaging regional CBF of preterm brains, but must be optimized for the extremely slow blood velocity unique in preterm brains. In this study, we explored the spatiotemporal CBF distribution in newborns scanned at the age of 32-45PMW using a pseudo-continuous ASL (pCASL) protocol adapted to slow blood flow in neonates. A total of 89 neonates were recruited. PCASL MRI was acquired from 34 normal newborns and phase contrast (PC) images from 19 newborns. Diffusion tensor images (DTI) were acquired from all 89 neonates for measuring cortical fractional anisotropy (FA), which characterizes cortical microstructure. Reproducible CBF measurements were obtained with the adjusted pCASL sequence. Global CBF measurement based on PC MRI was found to double its value in the 3rd trimester. Regional CBF increases were heterogeneous across the brain with a significantly higher rate of CBF increase in the frontal lobe and a lower rate of CBF increase in the occipital lobe. A significant correlation was found between frontal cortical CBF and cortical FA measurements (p<0.01). Increasing CBF values observed in the frontal lobe corresponded to lower FA values, suggesting that dendritic arborization and synaptic formation might be associated with an elevated local CBF. These results offer a preliminary account of heterogeneous regional CBF increases in a vital early developmental period and may shed the light on underlying metabolic support for cortical microstructural changes during the developmental period of 32-45PMW. Preterm effects and limitations of pCASL techniques in newborns need to be carefully considered for interpretation these results. [ABSTRACT FROM AUTHOR]

Cerebrovascular reactivity (CVR), the ability of cerebral vessels to dilate or constrict, has been shown to provide valuable information in the diagnosis and treatment evaluation of patients with various cerebrovascular conditions. CVR mapping is typically performed using hypercapnic gas inhalation as a vasoactive challenge while collecting BOLD images, but the inherent need of gas inhalation and the associated apparatus setup present a practical obstacle in applying it in routine clinical use. Therefore, we aimed to develop a new method to map CVR using resting-state BOLD data without the need of gas inhalation. This approach exploits the natural variation in respiration and measures its influence on BOLD MRI signal. In this work, we first identified a surrogate of the arterial CO 2 fluctuation during spontaneous breathing from the global BOLD signal. Second, we tested the feasibility and reproducibility of the proposed approach to use the above-mentioned surrogate as a regressor to estimate voxel-wise CVR. Third, we validated the “resting-state CVR map” with a conventional CVR map obtained with hypercapnic gas inhalation in healthy volunteers. Finally, we tested the utility of this new approach in detecting abnormal CVR in a group of patients with Moyamoya disease, and again validated the results using the conventional gas inhalation method. Our results showed that global BOLD signal fluctuation in the frequency range of 0.02–0.04 Hz contains the most prominent contribution from natural variation in arterial CO 2 . The CVR map calculated using this signal as a regressor is reproducible across runs (ICC=0.91±0.06), and manifests a strong spatial correlation with results measured with a conventional hypercapnia-based method in healthy subjects (r=0.88, p<0.001). We also found that resting-state CVR was able to identify vasodilatory deficit in patients with steno-occlusive disease, the spatial pattern of which matches that obtained using the conventional gas method (r=0.71±0.18). These results suggest that CVR obtained with resting-state BOLD may be a useful alternative in detecting vascular deficits in clinical applications when gas challenge is not feasible. [ABSTRACT FROM AUTHOR]

Diagnosis and treatment monitoring of cerebrovascular diseases routinely require hemodynamic imaging of the brain. Current methods either only provide part of the desired information or require the injection of multiple exogenous agents. In this study, we developed a multiparametric imaging scheme for the imaging of brain hemodynamics and function using gas-inhalation MRI. The proposed technique uses a single MRI scan to provide simultaneous measurements of baseline venous cerebral blood volume (vCBV), cerebrovascular reactivity (CVR), bolus arrival time (BAT), and resting-state functional connectivity (fcMRI). This was achieved with a novel, concomitant O 2 and CO 2 gas inhalation paradigm, rapid MRI image acquisition with a 9.3 min BOLD sequence, and an advanced algorithm to extract multiple hemodynamic information from the same dataset. In healthy subjects, CVR and vCBV values were 0.23±0.03%/mmHg and 0.0056±0.0006%/mmHg, respectively, with a strong correlation (r=0.96 for CVR and r=0.91 for vCBV) with more conventional, separate acquisitions that take twice the scan time. In patients with Moyamoya syndrome, CVR in the stenosis-affected flow territories (typically anterior-cerebral-artery, ACA, and middle-cerebral-artery, MCA, territories) was significantly lower than that in posterior-cerebral-artery (PCA), which typically has minimal stenosis, flow territories (0.12±0.06%/mmHg vs. 0.21±0.05%/mmHg, p <0.001). BAT of the gas bolus was significantly longer ( p =0.008) in ACA/MCA territories, compared to PCA, and the maps were consistent with the conventional contrast-enhanced CT perfusion method. FcMRI networks were robustly identified from the gas-inhalation MRI data after factoring out the influence of CO 2 and O 2 on the signal time course. The spatial correspondence between the gas-data-derived fcMRI maps and those using a separate, conventional fcMRI scan was excellent, showing a spatial correlation of 0.58±0.17 and 0.64±0.20 for default mode network and primary visual network, respectively. These findings suggest that advanced gas-inhalation MRI provides reliable measurements of multiple hemodynamic parameters within a clinically acceptable imaging time and is suitable for patient examinations. [ABSTRACT FROM AUTHOR]

• A novel MRI technique was developed to provide a non-invasive assessment of oxygen extraction fraction in the medial temporal lobe (MTL-OEF) in less than 5 minutes. • MTL-OEF was measured to be 23.9±3.6% in healthy adults and was significantly lower (P <0.0001) than the OEF of 33.3±2.9% in superficial cortical tissues. • In caffeine ingestion challenges, MTL-OEF was elevated by 9.1±4.0%. • MTL-OEF increased with age (MTL-OEF=20.997+0.100 × age; P =0.02). The medial temporal lobe (MTL) is a key area implicated in many brain diseases, such as Alzheimer's disease. As a functional biomarker, the oxygen extraction fraction (OEF) of MTL may be more sensitive than structural atrophy of MTL, especially at the early stages of diseases. However, there is a lack of non-invasive techniques to measure MTL-OEF in humans. The goal of this work is to develop an MRI technique to assess MTL-OEF in a clinically practical time without using contrast agents. The proposed method measures venous oxygenation (Y v) in the basal veins of Rosenthal (BVs), which are the major draining veins of the MTL. MTL-OEF can then be estimated as the arterio-venous difference in oxygenation. We developed an MRI sequence, dubbed arterial-suppressed accelerated T 2 -relaxation-under-phase-contrast (AS-aTRUPC), to quantify the blood T 2 of the BVs, which was then converted to Y v through a well-established calibration model. MTL-OEF was calculated as (Y a −Y v)/Y a × 100%, where Y a was the arterial oxygenation. The feasibility of AS-aTRUPC to quantify MTL-OEF was evaluated in 16 healthy adults. The sensitivity of AS-aTRUPC in detecting OEF changes was assessed by a caffeine ingestion (200 mg) challenge. For comparison, T 2 -relaxation-under-spin-tagging (TRUST) MRI, which is a widely used global OEF technique, was also acquired. The dependence of MTL-OEF on age was examined by including another seven healthy elderly subjects. The results showed that in healthy adults, MTL-OEF of the left and right hemispheres were correlated (P =0.005). MTL-OEF was measured to be 23.9±3.6% (mean±standard deviation) and was significantly lower (P <0.0001) than the OEF of 33.3±2.9% measured in superior sagittal sinus (SSS). After caffeine ingestion, there was an absolute percentage increase of 9.1±4.0% in MTL-OEF. Additionally, OEF in SSS measured with AS-aTRUPC showed a strong correlation with TRUST OEF (intra-class correlation coefficient=0.94 with 95% confidence interval [0.91, 0.96]), with no significant bias (P =0.12). MTL-OEF was found to increase with age (MTL-OEF=20.997+0.100 × age; P =0.02). In conclusion, AS-aTRUPC MRI provides non-invasive assessments of MTL-OEF and may facilitate future clinical applications of MTL-OEF as a disease biomarker. [ABSTRACT FROM AUTHOR]

The requirement for large aircraft components to have Al-Zn-Mg-Cu alloys with high strength and low quenching sensitivity has been increasing. The quenching sensitivity of 7085 and 7050 alloys used for thick plate applications was characterized via hardness tests and microstructure observation. A quenching precipitation model was established to predict the evolution of grain boundary and intragranular precipitates during air quenching process, and the effect of composition on the quenching precipitation behavior was investigated using this model. The quenching precipitation kinetic results show that the 7085 alloy has a low quenching sensitivity because the density of the precipitates in the Al 3 Zr dispersoids and at the grain boundary is lower compared with that of the 7050 alloy. This result is in agreement with experimental results. Furthermore, the thermodynamic calculation results illustrate that the increase in the Zn/Mg ratio and the decrease in Cu element cause the α phase region to expand, thereby reducing the quenching sensitivity of the 7085 alloy. [ABSTRACT FROM AUTHOR]

Purpose: Knowledge of blood T1 and T2 is of major importance in many applications of MRI in neonates. However, to date, there has not been a systematic study to examine neonatal blood T1/T2 relaxometry. This present study aims to investigate this topic. Methods: Using freshly collected blood samples from human umbilical cord, we performed in vitro experiments under controlled physiological conditions to measure blood T1 and T2 at 3 Tesla (T) and their dependence on several factors, including hematocrit (Hct), oxygenation (Y) and temperature. Results: The arterial T1 in neonates was 1825 ± 184 ms (Hct = 0.42 ± 0.08), longer than that of adult blood. Neonatal blood T1 was strongly dependent on Hct (P<0.001) and Y (P = 0.005), and the dependence of T1 on Y was more prominent at higher Hct. The arterial T2 of neonatal blood was 191 ms at an Hct of 0.42, which was also longer than adult blood. Neonatal blood T2 was positively associated with blood oxygenation and negatively associated with hematocrit level, and can be characterized by an exchange model. Neonatal blood T1 was also positively associated with temperature (P<0.001). Conclusion: The values provided in this report may provide important reference and calibration information for sequence optimization and quantification of in vivo neonatal MRI studies. [ABSTRACT FROM AUTHOR]

Purpose Venous oxygenation (Yv) is an important index of brain physiology and may be indicative of brain diseases. A T2-relaxation-under-spin-tagging (TRUST) MRI technique was recently developed to measure Yv. A multisite evaluation of this technique would be an important step toward broader availability and potential clinical utilizations of Yv measures. Methods TRUST MRI was performed on a total of 250 healthy subjects, 125 from the developer's site and 25 each from five other sites. All sites were equipped with a 3 Tesla (T) MRI of the same vendor. The estimated Yv and the standard error (SE) of the estimation εYv were compared across sites. Results The averaged Yv and εYv across six sites were 61.1% ± 1.4% and 1.3% ± 0.2%, respectively. Multivariate regression analysis showed that the estimated Yv was dependent on age ( P = 0.009) but not on performance site. In contrast, the SE of the Yv estimation was site-dependent ( P = 0.024) but was less than 1.5%. Further analysis revealed that εYv was positively associated with the amount of subject motion ( P < 0.001) but negatively associated with blood signal intensity ( P < 0.001). Conclusion This work suggests that TRUST MRI can yield equivalent results of Yv estimation across different sites. Magn Reson Med 75:680-687, 2016. © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

The pre-mRNA splicing regulator serine-arginine protein kinase 1 (SRPK1) promotes cancer development and various pathophysiological processes. However, the clinical relevance of SRPK1 in hepatocellular carcinoma (HCC) is not clear. This study investigates the expression and prognostic value of SRPK1 in HCC. We found that SRPK1 expression was significantly upregulated at the mRNA and protein level in all HCC cell lines or HCC tissue samples compared with the hepatic cell line or matched noncancerous tissue samples, respectively. Higher SRPK1 expression significantly correlated with clinical staging ( p = 0.031), survival time ( p = 0.004), and gender ( p = 0.011) of HCC patients. Together, our study showed that SRPK1 is overexpressed in HCC and may be a promising indicator of prognosis for HCC patients. [ABSTRACT FROM AUTHOR]