Regional fractional ventilation mapping in spontaneously breathing mice using hyperpolarized 129Xe MRI

The feasibility of ventilation imaging with hyperpolarized (HP) ¹²⁹Xe MRI has been investigated for quantitative and regional assessment of ventilation in spontaneously breathing mice. The multiple breath ventilation imaging technique was modified to the protocol of spontaneous inhalation of HP ¹²⁹Xe delivered continuously from a ¹²⁹Xe polarizer. A series of ¹²⁹Xe ventilation images was obtained by varying the number of breaths before the ¹²⁹Xe lung imaging. The fractional ventilation, r, was successfully evaluated for spontaneously breathing mice. An attempt was made to detect ventilation dysfunction in the emphysematous mouse lung induced by intratracheal administration of porcine pancreatic elastase (PPE). As a result, the distribution of fractional ventilation could be visualized by the r map. Significant dysfunction of ventilation was quantitatively identified in the PPE‐treated group. The whole‐lung r value of 0.34 ± 0.01 for control mice (N = 4) was significantly reduced, to 0.25 ± 0.07, in PPE‐treated mice (N = 4) (p = 0.038). This study is the first application of multiple breath ventilation imaging to spontaneously breathing mice, and shows that this methodology is sensitive to differences in the pulmonary ventilation. This methodology is expected to improve simplicity as well as noninvasiveness when assessing regional ventilation in small rodents. Copyright © 2014 John Wiley & Sons, Ltd.     

Comparison of hyperpolarized (3)He MRI with Xe-enhanced computed tomography imaging for ventilation mapping of rat lung

Lung ventilation was mapped in five healthy Brown Norway rats (210–377 g) using both hyperpolarized ³He MRI and Xe‐enhanced computed tomography (Xe‐CT) under similar ventilator conditions. Whole‐lung measurements of ventilation r obtained with ³He MRI were not significantly different from those obtained from Xe‐CT (p = 0.1875 by Wilcoxon matched pairs test). The ventilation parameter r is defined as the fraction of refreshed gas per unit volume per breath. Regional ventilation was also measured in four regions of the lung using both methods. A two‐tailed paired t‐test was performed for each region, yielding p > 0.05 for all but the upper portion of the right lung. The distribution of regional ventilation was evaluated by calculating ventilation gradients in the superior/inferior (S/I) direction. The average S/I gradient obtained using the ³He MRI method was found to be 0.17 ± 0.04 cm^?1, whereas the average S/I gradient obtained using the Xe‐CT method was found to be 0.016 ± 0.005 cm^?1. In general, S/I ventilation gradients obtained from both methods were significantly different from each other (p = 0.0019 by two‐tailed paired t‐test). These regional differences in ventilation measurements may be caused by the manner in which the gas contrast agents distribute physiologically and/or by the imaging modality. Copyright © 2011 John Wiley & Sons, Ltd.     

Exercising calf muscle changes correlate with pH,PCr recovery and maximum oxidative phosphorylation

Skeletal muscle metabolism is impaired in disorders like diabetes mellitus or peripheral vascular disease. The skeletal muscle echo planar imaging (EPI) signal (S_EPI) and its relation to energy metabolism are still debated. Localised 31P MRS and S_EPI data from gastrocnemius medialis of 19 healthy subjects were combined in one scanning session to study direct relationships between phosphocreatine (PCr), pH kinetics and parameters of time courses. Dynamic spectroscopy (semi‐LASER) and EPI were performed immediately before, during and after 5 min of plantar flexions. Data were acquired in a 7 T MR scanner equipped with a custom‐built ergometer and a dedicated ³¹P/¹H radio frequency (RF) coil array. Using a form‐fitted multi‐channel ³¹P/¹H coil array resulted in high signal‐to‐noise ratio (SNR). PCr and pH in the gastrocnemius medialis muscle were quantified from each ³¹P spectrum, acquired every 6 s. During exercise, S_EPI(t) was found to be a linear function of tissue pH(t) (cross‐correlation r = –0.85 ± 0.07). Strong Pearson's correlations were observed between post exercise time‐to‐peak (TTP) of S_EPI and (a) the time constant of PCr recovery τ_{PCr recovery} (r = 0.89, p < 10^{? 6}), (b) maximum oxidative phosphorylation using the linear model, Q_{max, lin} (r = 0.65, p = 0.002), the adenosine‐diphosphate‐driven model, Q_max,ADP (r = 0.73, p = 0.0002) and (c) end exercise pH (r = 0.60, p = 0.005). Based on combined accurately localised 31P MRS and weighted MRI, both with high temporal resolution, strong correlations of the skeletal muscle S_EPI during exercise and tissue pH time courses and of post exercise S_EPI and parameters of energy metabolism were observed. In conclusion, a tight coupling between skeletal muscle metabolic activity and tissue signal weighting, probably induced by osmotically driven water shift, exists and can be measured non‐invasively, using NMR at 7 T. © 2014 The Authors. NMR in Biomedicine published by John Wiley & Sons, Ltd.     

Hyperpolarized 129Xe MRI using isobutene as a new quenching gas

The use of a quenching gas, isobutene, with a low vapor pressure was investigated to enhance the utility of hyperpolarized ¹²⁹Xe (HP Xe) MRI. Xenon mixed with isobutene was hyperpolarized using a home‐built apparatus for continuously producing HP Xe. The isobutene was then readily liquefied and separated almost totally by continuous condensation at about 173 K, because the vapor pressure of isobutene (0.247 kPa) is much lower than that of Xe (157 kPa). Finally, the neat Xe gas was continuously delivered to mice by spontaneous inhalation. The HP Xe MRI was enhanced twofold in polarization level and threefold in signal intensity when isobutene was adopted as the quenching gas instead of N₂. The usefulness of the HP Xe MRI was verified by application to pulmonary functional imaging of spontaneously breathing mice, where the parameters of fractional ventilation (r_a) and gas exchange (f_D) were evaluated, aiming at future extension to preclinical studies. This is the first application of isobutene as a quenching gas for HP Xe MRI.     

Higher Plasma Myeloperoxidase Levels Are Not Associated with an Increased Risk for Cardiovascular Events in HIV-Infected Adults

Abstract

Objectives: Elevated myeloperoxidase (MPO) levels are predictive of high cardiovascular (CV) risk in the general population. The value of MPO as a CV marker in the HIV population has not been investigated. Method: Medical records were reviewed to identify HIV+ patients with a documented CV event (myocardial ischemia/infarction) and stored plasma samples within 12 months prior to the event. HIV+ adults with no CV history and with similarly available stored plasma samples were site-, age-, and gender-matched 1:1 to cases. Results: We identified 124 participants (62 case-control pairs): 94% male, median age 46 years. Median (IQR) MPO levels (pmoles/L) were lower in cases vs. controls: 292 (235–376) vs. 320 (249–467); p = .004. Cases were more likely to have other CV risk factors, including smoking, hypertension, and higher cholesterol and triglycerides. The observed MPO directional difference persisted after controlling for CV risk factors. In the reduced model, observed differences in MPO remained independently and negatively associated with CV event (p = .03) after adjusting for two positively associated risk factors, differences in cholesterol levels (p = .01), and differences in smoking history (ever smoked vs. never smoked; p = .04). Differences in triglyceride levels and hypertension were not statistically significant independent risk factors in this sample (p > .05). Within cases, MPO was negatively correlated with CD4 count (r_s = –0. 40, p = .0023) and age (r_s = ?0. 34, p = .01). In contrast, age at blood draw was positively correlated with MPO in controls (r_s = 0.28, p = .031) and CD4 was uncorrelated (r_s = ?0. 01, p > .9). No other factors were significantly correlated with MPO within groups. Conclusion: In contrast to the general population, higher MPO levels were not predictive of CV events in this study, underscoring the fact that pathways operative in HIV arteriopathy may be distinct from traditional CV disease pathogenesis.     

Development of a fast method for quantitative measurement of hyperpolarized 129Xe dynamics in mouse brain

A fast method has been established for the precise measurement and quantification of the dynamics of hyperpolarized (HP) xenon‐129 (¹²⁹Xe) in the mouse brain. The key technique is based on repeatedly applying radio frequency (RF) pulses and measuring the decrease of HP ¹²⁹Xe magnetization after the brain Xe concentration has reached a steady state due to continuous HP ¹²⁹Xe ventilation. The signal decrease of the ¹²⁹Xe nuclear magnetic resonance (NMR) signal was well described by a simple theoretical model. The technique made it possible to rapidly evaluate the rate constant α, which is composed of cerebral blood flow (CBF), the partition coefficient of Xe between the tissue and blood (λ_i), and the longitudinal relaxation time (T_1i) of HP ¹²⁹Xe in the brain tissue, without any effect of depolarization by RF pulses and the dynamics in the lung. The technique enabled the precise determination of α as 0.103 ± 0.018 s^‐1 (± SD, n = 5) on healthy mice. To investigate the potential of this method for detecting physiological changes in the brain of a kainic acid (KA) ‐induced mouse model of epilepsy, an attempt was made to follow the time course of α after KA injection. It was found that the α value changes characteristically with time, reflecting the change in the physiological state of the brain induced by KA injection. By measuring CBF using ¹H MRI and ¹²⁹Xe dynamics simultaneously and comparing these results, it was suggested that the reduction of T_1i, in addition to the increase of CBF due to KA‐induced epilepsy, are possible causes of the change in ¹²⁹Xe dynamics. Thus, the present method would be useful to detect a pathophysiological state in the brain and provide a novel tool for future brain study. Copyright © 2011 John Wiley & Sons, Ltd.     

Apparent diffusion coefficients in prostate cancer: correlation with molecular markers Ki‐67, HIF‐1α and VEGF

Prostate cancer (PCa) is the second most common cancer in men. The Gleason score (GS) and biomarkers play important roles in the diagnosis and treatment of patients with PCa. The purpose of this study was to investigate the relationship between the apparent diffusion coefficient (ADC) and the molecular markers Ki‐67, hypoxia‐inducible factor‐1α (HIF‐1α) and vascular endothelial growth factor (VEGF) in PCa. Thirty‐nine patients with 39 lesions, who had been diagnosed with PCa, were enrolled in this study. All patients underwent diffusion‐weighted magnetic resonance imaging (DW‐MRI) (b = 800 s/mm²). The expression of Ki‐67, HIF‐1α and VEGF was assessed by immunohistochemistry. Statistical analysis was applied to analyze the association between ADC and prostate‐specific antigen (PSA), GS and the expression of Ki‐67, HIF‐1α and VEGF. The group differences in ADC among different grades of Ki‐67, HIF‐1α and VEGF were also analyzed. The mean ± standard deviation of ADC was (0.76 ± 0.27) × 10^?3 mm²/s. ADC correlated negatively with PSA and GS (p < 0.05). The Ki‐67 staining index (SI), HIF‐1α expression and VEGF expression in PCa were correlated inversely with ADC, controlling for age (r = –0.332, p < 0.05; r = ?0.662, p < 0.0005; and r = ?0.714, p < 0.0005, respectively). ADC showed a significant difference among different grades of Ki‐67 (F = 9.164, p = 0.005), HIF‐1α (F = 40.333, p < 0.0005) and VEGF (F = 22.048, p < 0.0005). In conclusion, ADC was correlated with PSA, GS, and Ki‐67, HIF‐1α and VEGF expression in patients with PCa. ADC may be used to evaluate tumor proliferation, hypoxia and angiogenesis in PCa.     

Sexual dimorphism in hepatic lipids is associated with the evolution of metabolic status in mice

Ectopic lipid accumulation in the liver is implicated in metabolic disease in an age‐ and sex‐dependent manner. The role of hepatic lipids has been well established within the scope of metabolic insults in mice, but has been insufficiently characterized under standard housing conditions, where age‐related metabolic alterations are known to occur. We studied a total of 10 male and 10 female mice longitudinally. At 3, 7 and 11 months of age, non‐invasive ¹H‐magnetic resonance spectroscopy (¹H‐MRS) was used to monitor hepatic lipid content (HLC) and fatty acid composition in vivo, and glucose homeostasis was assessed with glucose and insulin challenges. At the end of the study, hepatic lipids were comprehensively characterized by nuclear magnetic resonance (NMR) and liquid chromatography‐mass spectrometric analyses of liver tissue samples. In males, HLC increased from 1.4 ± 0.1% at 3 months to 2.9 ± 0.3% at 7 months (p < 0.01) and 2.7 ± 0.3% at 11 months (p < 0.05), in correlation with fasting insulin levels (p < 0.01, r = 0.51) and parameters from the insulin tolerance test (ITT; p < 0.001, r = –0.69 versus area under the curve; p < 0.01, r = –0.57 versus blood glucose drop at 1 h post‐ITT; p < 0.01, r = 0.55 versus blood glucose at 3 h post‐ITT). The metabolic performance of females remained the same throughout the study, and HLC was higher than that of males at 3 months (2.7 ± 0.2%, p < 0.01), but comparable at 7 months (2.2 ± 0.2%) and 11 months (2.2 ± 0.1%). Strong sexual dimorphism in bioactive lipid species, including diacylglycerols (higher in males, p < 0.0001), phosphatidylinositols (higher in females, p < 0.001) and omega‐3 polyunsaturated fatty acids (higher in females, p < 0.01), was found to be in good correlation with metabolic scores at 11 months. Therefore, in mice housed under standard conditions, sex‐specific composition of bioactive lipids is associated with metabolic protection in females, whose metabolic performance was independent of hepatic cytosolic lipid content.     

Preclinical hyperpolarized 129Xe MRI: ventilation and T2* mapping in mouse lungs at 7 T using multi‐echo flyback UTE

Fast apparent transverse relaxation (short T₂*) is a common obstacle when attempting to perform quantitative ¹H MRI of the lungs. While T₂* times are longer for pulmonary hyperpolarized (HP) gas functional imaging (in particular for gaseous ¹²⁹Xe), T₂* can still lead to quantitative inaccuracies for sequences requiring longer echo times (such as diffusion weighted images) or longer readout duration (such as spiral sequences). This is especially true in preclinical studies, where high magnetic fields lead to shorter relaxation times than are typically seen in human studies. However, the T₂* of HP ¹²⁹Xe in the most common animal model of human disease (mice) has not been reported. Herein, we present a multi‐echo radial flyback imaging sequence and use it to measure HP ¹²⁹Xe T₂* at 7 T under a variety of respiratory conditions. This sequence mitigates the impact of T₁ relaxation outside the animal by using multiple gradient‐refocused echoes to acquire images at a number of effective echo times for each RF excitation. After validating the sequence using a phantom containing water doped with superparamagnetic iron oxide nanoparticles, we measured the ¹²⁹Xe T₂* in vivo for 10 healthy C57Bl/6 J mice and found T₂* ~ 5 ms in the lung airspaces. Interestingly, T₂* was relatively constant over all experimental conditions, and varied significantly with sex, but not age, mass, or the O₂ content of the inhaled gas mixture. These results are discussed in the context of T₂* relaxation within porous media.     

Fractional ventilation mapping using inert fluorinated gas MRI in rat models of inflammation and fibrosis

The purpose of this study was to extend established methods for fractional ventilation mapping using ¹⁹F MRI of inert fluorinated gases to rat models of pulmonary inflammation and fibrosis. In this study, five rats were instilled with lipopolysaccharide (LPS) in the lungs two days prior to imaging, six rats were instilled with bleomycin in the lungs two weeks prior to imaging and an additional four rats were used as controls. ¹⁹F MR lung imaging was performed at 3 T with rats continuously breathing a mixture of sulfur hexafluoride and O₂. Fractional ventilation maps were obtained using a wash‐out approach, by switching the breathing mixture to pure O₂, and acquiring images following each successive wash‐out breath. The mean fractional ventilation (r) was 0.29 ± 0.05 for control rats, 0.23 ± 0.10 for LPS‐instilled rats and 0.19 ± 0.03 for bleomycin‐instilled rats. Bleomycin‐instilled rats had a significantly decreased mean r value compared with controls (P = 0.010). Although LPS‐instilled rats had a slightly reduced mean r value, this trend was not statistically significant (P = 0.556). Fractional ventilation gradients were calculated in the anterior/posterior (A/P) direction, and the mean A/P gradient was ?0.005 ± 0.008 cm^?1 for control rats, 0.013 ± 0.005 cm^?1 for LPS‐instilled rats and 0.009 ± 0.018 cm^?1 for bleomycin‐instilled rats. Fractional ventilation gradients were significantly different for control rats compared with LPS‐instilled rats only (P = 0.016). The ventilation gradients calculated from control rats showed the expected gravitational relationship, while ventilation gradients calculated from LPS‐ and bleomycin‐instilled rats showed the opposite trend. Histology confirmed that LPS‐instilled rats had a significantly elevated alveolar wall thickness, while bleomycin‐instilled rats showed signs of substantial fibrosis. Overall, ¹⁹F MRI may be able to detect the effects of pulmonary inflammation and fibrosis using a simple and inexpensive imaging approach that can potentially be translated to humans. Copyright © 2016 John Wiley & Sons, Ltd.     

Quantitative evaluation of pulmonary gas‐exchange function using hyperpolarized 129Xe CEST MRS and MRI

Hyperpolarized ¹²⁹Xe gas MR has been a powerful tool for evaluating pulmonary structure and function due to the extremely high enhancement in spin polarization, the good solubility in the pulmonary parenchyma, and the excellent chemical sensitivity to its surrounding environment. Generally, the quantitative structural and functional information of the lung are evaluated using hyperpolarized ¹²⁹Xe by employing the techniques of chemical shift saturation recovery (CSSR) and xenon polarization transfer contrast (XTC). Hyperpolarized ¹²⁹Xe chemical exchange saturation transfer (Hyper‐CEST) is another method for quantifying the exchange information of hyperpolarized ¹²⁹Xe by using the exchange of xenon signals according to its different chemical shifts, and it has been widely used in biosensor studies in vitro. However, the feasibility of using hyperpolarized ¹²⁹Xe CEST to quantify the pulmonary gas exchange function in vivo is still unclear. In this study, the technique of CEST was used to quantitatively evaluate the gas exchange in the lung globally and regionally via hyperpolarized ¹²⁹Xe MRS and MRI, respectively. A new parameter, the pulmonary apparent gas exchange time constant (T_app), was defined, and it increased from 0.63 s to 0.95 s in chronic obstructive pulmonary disease (COPD) rats (induced by cigarette smoke and lipopolysaccharide exposure) versus the controls with a significant difference (P = 0.001). Additionally, the spatial distribution maps of T_app in COPD rats' pulmonary parenchyma showed a regionally obvious increase compared with healthy rats. These results indicated that hyperpolarized ¹²⁹Xe CEST MR was an effective method for globally and regionally quantifying the pulmonary gas exchange function, which would be helpful in diagnosing lung diseases that are related to gas exchange, such as COPD.     

A protocol for quantifying cardiogenic oscillations in dynamic 129Xe gas exchange spectroscopy: The effects of idiopathic pulmonary fibrosis

The spectral parameters of hyperpolarized ¹²⁹Xe exchanging between airspaces, interstitial barrier, and red blood cells (RBCs) are sensitive to pulmonary pathophysiology. This study sought to evaluate whether the dynamics of ¹²⁹Xe spectroscopy provide additional insight, with particular focus on quantifying cardiogenic oscillations in the RBC resonance. ¹²⁹Xe spectra were dynamically acquired in eight healthy volunteers and nine subjects with idiopathic pulmonary fibrosis (IPF). ¹²⁹Xe FIDs were collected every 20 ms (T_E = 0.932 ms, 512 points, dwell time = 32 μs, flip angle ≈ 20°) during a 16 s breathing maneuver. The FIDs were pre‐processed using the spectral improvement by Fourier thresholding technique (SIFT) and fit in the time domain to determine the airspace, interstitial barrier, and RBC spectral parameters. The RBC and gas resonances were fit to a Lorentzian lineshape, while the barrier was fit to a Voigt lineshape to account for its greater structural heterogeneity. For each complex resonance the amplitude, chemical shift, linewidth(s), and phase were calculated. The time‐averaged spectra confirmed that the RBC to barrier amplitude ratio (RBC:barrier ratio) and RBC chemical shift are both reduced in IPF subjects. Their temporal dynamics showed that all three ¹²⁹Xe resonances are affected by the breathing maneuver. Most notably, several RBC spectral parameters exhibited prominent oscillations at the cardiac frequency, and their peak‐to‐peak variation differed between IPF subjects and healthy volunteers. In the IPF cohort, oscillations were more prominent in the RBC amplitude (16.8 ± 5.2 versus 9.7 ± 2.9%; P = 0.008), chemical shift (0.43 ± 0.33 versus 0.083 ± 0.05 ppm; P < 0.001), and phase (7.7 ± 5.6 versus 1.4 ± 0.8°; P < 0.001). Dynamic ¹²⁹Xe spectroscopy is a simple and sensitive tool that probes the temporal variability of gas exchange and may prove useful in discerning the underlying causes of its impairment.     

Variability in fasting lipid and glycogen contents in hepatic and skeletal muscle tissue in subjects with and without type 2 diabetes: a 1H and 13C MRS study

The measurement of tissue lipid and glycogen contents and the establishment of normal levels of variability are important when assessing changes caused by pathology or treatment. We measured hepatic and skeletal muscle lipid and glycogen levels using ¹H and ¹³C MRS at 3 T in groups of subjects with and without type 2 diabetes. Within‐visit reproducibility, due to repositioning and instrument errors was determined from repeat measurements made over 1 h. Natural variability was assessed from separate measurements made on three occasions over 1 month. Hepatic lipid content was greater in subjects with diabetes relative to healthy subjects (p = 0.03), whereas levels of hepatic and skeletal muscle glycogen, and of intra‐ and extra‐myocellular lipid, were similar. The single‐session reproducibility values (coefficient of variation, CV) for hepatic lipid content were 12% and 7% in groups of subjects with and without diabetes, respectively. The variability of hepatic lipid content over 1 month was greater than the reproducibility, with CV = 22% (p = 0.08) and CV = 44% (p = 0.004) in subjects with and without diabetes, respectively. Similarly, levels of variation in basal hepatic glycogen concentrations (subjects with diabetes, CV = 38%; healthy volunteers, CV = 35%) were significantly larger than single‐session reproducibility values (CV = 17%, p = 0.02 and CV = 13%, p = 0.05, respectively), indicating substantial biological changes in basal concentrations over 1 month. There was a decreasing correlation in measurements of both hepatic lipid and glycogen content with increasing time between scans. Levels of variability in intra‐ and extra‐myocellular lipid in the soleus muscle, and glycogen concentrations in the gastrocnemius muscle, tended to be larger than expected from single‐session reproducibility, although these did not reach significance. Copyright © 2013 John Wiley & Sons, Ltd.     

Characterization of clear cell renal cell carcinoma with diffusion kurtosis imaging: correlation between diffusion kurtosis parameters and tumor cellularity

The aim of this study was to evaluate the role of diffusion kurtosis imaging (DKI) in the characterization of clear cell renal cell carcinoma (ccRCC) and to correlate DKI parameters with tumor cellularity. Fifty‐nine patients with pathologically diagnosed ccRCCs were evaluated by DKI on a 3‐T scanner. Regions of interest were drawn on the maps of the mean diffusion coefficient (MD) and mean diffusion kurtosis (MK). All ccRCCs were histologically graded according to the Fuhrman classification system. Tumor cellularity was measured by the nuclear‐to‐cytoplasm (N/C) ratio and the number of tumor cell nuclei (NTCN). ccRCCs were classified as grade 1 (n = 23), grade 2 (n = 24), grade 3 (n = 10) and grade 4 (n = 3). Both MD and MK could readily discriminate between normal renal parenchyma and ccRCCs (p < 0.001), and receiver operating characteristic (ROC) curve analysis showed that MK exhibited a better performance with an area under the ROC curve of 0.874 and sensitivity/specificity of 68.33%/100% (p < 0.001). Further, MD and MK were significantly different between grade 1 and grades 3 and 4 (p = 0.01, p < 0.001) and between grade 2 and grades 3 and 4 (p = 0.015, p < 0.005), respectively. However, no significant difference was found between grade 1 and grade 2 (p > 0.05) for both MD and MK. With regard to NTCN, no significant difference was found between any two grades (p > 0.05), and the N/C ratio changed significantly with grade (p < 0.01, between any two grades). Negative correlations were found between MK and MD (r = –0.56, p < 0.001), and between MD and N/C ratio (r = –0.36, p < 0.005), whereas MK and the N/C ratio were positively correlated (r = 0.45, p = 0.003). DKI could quantitatively characterize ccRCC with different grades by probing non‐Gaussian diffusion properties related to changes in the tumor microenvironment or tissue complexities in the tumor. Copyright © 2016 John Wiley & Sons, Ltd.     

High‐temporospatial‐resolution dynamic contrast‐enhanced (DCE) wrist MRI with variable‐density pseudo‐random circular Cartesian undersampling (CIRCUS) acquisition: evaluation of perfusion in rheumatoid arthritis patients

This study is to evaluate highly accelerated three‐dimensional (3D) dynamic contrast‐enhanced (DCE) wrist MRI for assessment of perfusion in rheumatoid arthritis (RA) patients. A pseudo‐random variable‐density undersampling strategy, circular Cartesian undersampling (CIRCUS), was combined with k–t SPARSE‐SENSE reconstruction to achieve a highly accelerated 3D DCE wrist MRI. Two healthy volunteers and 10 RA patients were studied. Two patients were on methotrexate (MTX) only (Group I) and the other eight were treated with a combination therapy of MTX and anti‐tumor necrosis factor (TNF) therapy (Group II). Patients were scanned at baseline and 3 month follow‐up. DCE MR images were used to evaluate perfusion in synovitis and bone marrow edema pattern in the RA wrist joints. A series of perfusion parameters was derived and compared with clinical disease activity scores of 28 joints (DAS28). 3D DCE wrist MR images were obtained with a spatial resolution of 0.3 × 0.3 × 1.5 mm³ and temporal resolution of 5 s (with an acceleration factor of 20). The derived perfusion parameters, most notably transition time (dT) of synovitis, showed significant negative correlations with DAS28‐ESR (r = ?0.80, p < 0.05) and DAS28‐CRP (r = ?0.87, p < 0.05) at baseline and also correlated significantly with treatment responses evaluated by clinical score changes between baseline and 3 month follow‐up (with DAS28‐ESR r = ?0.79, p < 0.05, and DAS28‐CRP r = ?0.82, p < 0.05). Highly accelerated 3D DCE wrist MRI with improved temporospatial resolution has been achieved in RA patients and provides accurate assessment of neovascularization and perfusion in RA joints, showing promise as a potential tool for evaluating treatment responses. Copyright © 2015 John Wiley & Sons, Ltd.     

Interactive effects of adiposity and insulin resistance on the impaired lung function in asthmatic adults: cross-sectional analysis of NHANES data

Background: Obesity is considered a risk factor for both asthma and insulin resistance in adults. Insulin resistance (IR) also influences pulmonary function in the non-obese population.

Aim: To investigate the modifying effect of insulin resistance on the predictive role of anthropometric measures in the estimation of impaired lung function among asthmatic adults.

Subjects and methods: A cross-sectional study of 1276 adults extracted from the NHANES 2009–2012 database was performed. Adjusted multiple linear regression was conducted to analyse the contributory role of obesity and IR in predicting lung function among asthmatic adults.

Results: BMI, waist circumference (WC) and waist-to-height ratio (WHtR) showed significantly negative correlations with FVC (r=–0.24, –0.18, –0.39, respectively; p?<?0.001), FEV1(r=–0.24, –0.21, –0.40, respectively; p?<?0.001) and FEF 25–75% (r=–0.15, –0.18, –0.27, respectively; p?<?0.001). Even after adjustment for the covariates (age, gender, smoking history and standing height), BMI and HOMA-IR had significant relationships with FVC (β=??10.3; p?<?0.01 and β=??16.0; p?<?0.05) and FEV1 (β=??8.7; p?<?0.01 and β=??11.7; p?<?0.05). BMI could significantly predict the decreased FVC (β=??13.7; p?<?0.01) and FEV1 (β=??10.7; p?<?0.01) only in the insulin resistant asthmatics.

Conclusion: WHtR and IR predict impaired lung function in overweight/obese asthmatic adults independently. IR also modifies the association between excessive adiposity and respiratory function in asthmatic adults.     

The Effect of Regional Variations of the Trabecular Bone Properties on the Compressive Strength of Human Vertebral Bodies

Cancellous centrum is a major component of the vertebral body and significantly contributes to its structural strength and fracture risk. We hypothesized that the variability of cancellous bone properties in the centrum is associated with vertebral strength. Microcomputed tomography (micro-CT)-based gray level density (GLD), bone volume fraction (BV/TV), and finite element modulus (E) were examined for different regions of the trabecular centrum and correlated with vertebral body strength determined experimentally. Two sets of images in the cancellous centrum were digitally prepared from micro-CT images of eight human vertebral bodies (T10–L5). One set included a cubic volume (1 per vertebral centrum, n = 8) in which the largest amount of cancellous material from the centrum was included but all the shell materials were excluded. The other set included cylindrical volumes (6 per vertebral centrum, n = 48) from the anterior (4 regions: front, center, left, and right of the midline of vertebra) and the posterior (2 regions: left and right) regions of the centrum. Significant positive correlations of vertebral strength with GLD (r ² = 0.57, p = 0.03) and E (r ² = 0.63, p = 0.02) of the whole centrum and with GLD (r ² = 0.65, p = 0.02), BV/TV (r ² = 0.72, p = 0.01) and E (r ² = 0.85, p = 0.001) of the central region of the vertebral centrum were found. Vertebral strength decreased with increasing coefficient of variation of GLD, BV/TV, and E calculated from subregions of the vertebral centrum. The values of GLD, BV/TV, and E in centrum were significantly smaller for the anterior region than for the posterior region. Overall, these findings supported the significant role of regional variability of centrum properties in determining the whole vertebral strength.     

Continuous‐wave saturation considerations for efficient xenon depolarization

The combination of hyperpolarized Xe with chemical exchange saturation transfer (Hyper‐CEST) is a powerful NMR technique to detect highly dilute concentrations of Xe binding sites using RF saturation pulses. Crucially, that combination of saturation pulse strength and duration that generates the maximal Hyper‐CEST effect is a priori unknown. In contrast to CEST in proton MRI, where the system reaches a steady‐state for long saturation times, Hyper‐CEST has an optimal saturation time, i.e. saturating for shorter or longer reduces the Hyper‐CEST effect. Here, we derive expressions for this optimal saturation pulse length. We also found that a pulse strength, B₁, corresponding to five times the Xe exchange rate, k_BA (i.e. B₁ = 5 k_BA/γ with the gyromagnetic ratio of ¹²⁹Xe, γ), generates directly and without further optimization 96 % of the maximal Hyper‐CEST contrast while preserving spectral selectivity. As a measure that optimizes the amplitude and the width of the Hyper‐CEST response simultaneously, we found an optimal saturation pulse strength corresponding to times the Xe exchange rate, i.e. . When extremely low host concentration is detected, then the expression for the optimum saturation time simplifies as it approaches the longitudinal relaxation time of free Xe. Copyright © 2015 John Wiley & Sons, Ltd.     

Oxygen‐dependent hyperpolarized 129Xe brain MR

Hyperpolarized (HP) ¹²⁹Xe MR offers unique advantages for brain functional imaging (fMRI) because of its extremely high sensitivity to different chemical environments and the total absence of background noise in biological tissues. However, its advancement and applications are currently plagued by issues of signal strength. Generally, xenon atoms found in the brain after inhalation are transferred from the lung via the bloodstream. The longitudinal relaxation time (T₁) of HP ¹²⁹Xe is inversely proportional to the pulmonary oxygen concentration in the lung because oxygen molecules are paramagnetic. However, the T₁ of ¹²⁹Xe is proportional to the pulmonary oxygen concentration in the blood, because the higher pulmonary oxygen concentration will result in a higher concentration of diamagnetic oxyhemoglobin. Accordingly, there should be an optimal pulmonary oxygen concentration for a given quantity of HP ¹²⁹Xe in the brain. In this study, the relationship between pulmonary oxygen concentration and HP ¹²⁹Xe signal in the brain was analyzed using a theoretical model and measured through in vivo experiments. The results from the theoretical model and experiments in rats are found to be in good agreement with each other. The optimal pulmonary oxygen concentration predicted by the theoretical model was 21%, and the in vivo experiments confirmed the presence of such an optimal ratio by reporting measurements between 25% and 35%. These findings are helpful for improving the ¹²⁹Xe signal in the brain and make the most of the limited spin polarization available for brain experiments. Copyright © 2016 John Wiley & Sons, Ltd.     

Correlation of Choline/Creatine and Apparent Diffusion Coefficient values with the prognostic parameters of Head and Neck Squamous Cell Carcinoma

The aim of this study was to measure choline/creatine (Ch/Cr) levels through ¹H‐MRS and apparent diffusion coefficient (ADC) values through diffusion‐weighted MRI, and to correlate these values with the prognostic parameters of head and neck squamous cell carcinoma (HNSCC). The institutional review board approved this study and informed written consent was obtained from all study participants. A prospective study of 43 patients (31 men and 12 women; mean age, 65 years) with HNSCC was conducted. Single‐voxel ¹H‐MRS was performed at the tumor or metastatic cervical lymph node with point‐resolved spectroscopy (PRESS) at TE = 135 ms. Diffusion‐weighted MR images with b values of 0, 500 and 1000 s/mm² and contrast MRI of the head and neck were performed. The Ch/Cr levels and ADC values of HNSCC were calculated. The gross tumor volume (GTV) was also calculated. The degree of tumor differentiation was determined through pathological examination. The HNSCC Ch/Cr level was negatively correlated with the ADC value (r = ?0.662, p = 0.001). There was a significant difference in the Ch/Cr and ADC values at different degrees of tumor differentiation (p = 0.003 and p = 0.001) and with different GTVs (p = 0.122 and p = 0.001). The following prognostic parameter categories were used: (i) poorly differentiated and undifferentiated versus well differentiated to moderately differentiated; and (ii) HNSCC with GTV < 30 cm³ versus GTV > 30 cm³. The cut‐off values for Cho/Cr and ADC for each category were 1.83, 0.95 and 1.94, 0.99, respectively, and the areas under the curve were 0.771, 0.967 and 0.726, 0.795, respectively, for each category. We conclude that the Ch/Cr levels determined using ¹H‐MRS and the ADC values are well correlated with several prognostic parameters of HNSCC. Copyright © 2016 John Wiley & Sons, Ltd.