Comparison of Dixon Sequences for Estimation of Percent Breast Fibroglandular Tissue

Objectives

To evaluate sources of error in the Magnetic Resonance Imaging (MRI) measurement of percent fibroglandular tissue (%FGT) using two-point Dixon sequences for fat-water separation.

Methods

Ten female volunteers (median age: 31 yrs, range: 23–50 yrs) gave informed consent following Research Ethics Committee approval. Each volunteer was scanned twice following repositioning to enable an estimation of measurement repeatability from high-resolution gradient-echo (GRE) proton-density (PD)-weighted Dixon sequences. Differences in measures of %FGT attributable to resolution, T₁ weighting and sequence type were assessed by comparison of this Dixon sequence with low-resolution GRE PD-weighted Dixon data, and against gradient-echo (GRE) or spin-echo (SE) based T₁-weighted Dixon datasets, respectively.

Results

%FGT measurement from high-resolution PD-weighted Dixon sequences had a coefficient of repeatability of ±4.3%. There was no significant difference in %FGT between high-resolution and low-resolution PD-weighted data. Values of %FGT from GRE and SE T₁-weighted data were strongly correlated with that derived from PD-weighted data (r = 0.995 and 0.96, respectively). However, both sequences exhibited higher mean %FGT by 2.9% (p < 0.0001) and 12.6% (p < 0.0001), respectively, in comparison with PD-weighted data; the increase in %FGT from the SE T₁-weighted sequence was significantly larger at lower breast densities.

Conclusion

Although measurement of %FGT at low resolution is feasible, T₁ weighting and sequence type impact on the accuracy of Dixon-based %FGT measurements; Dixon MRI protocols for %FGT measurement should be carefully considered, particularly for longitudinal or multi-centre studies.     

CD44 expression positively correlates with Foxp3 expression and suppressive function of CD4+ Treg cells

Background  

CD4⁺CD25⁺ regulatory T (T_reg) cells develop in the thymus and can suppress T cell proliferation, modulated by Foxp3 and cytokines; however, the relevance of CD44 in T_reg cell development is less clear. To address this issue, we analyzed Foxp3 expression in CD44⁺ T_reg cells by using multiple parameters, measured the levels of the immunoregulatory cytokine interleukin (IL)-10 in various thymocyte subsets, and determined the suppressor activity in different splenic T_reg cell populations.     

Influence of DPPE surface undulations on melting temperature determination: UV/Vis spectroscopic and MD study

One of the most distinguished quantities that describes lipid main phase transition, i.e. the transition from the gel (L_β(′)) to the fluid (L_α) phase, is its melting temperature (T_m). Because melting is accompanied by a large change in enthalpy the, L_β(′) → L_α transition can be monitored by various calorimetric, structural and spectroscopic techniques and T_m should be the same regardless of the metric monitored or the technique employed. However, in the case of DPPE multilamellar aggregates there is a small but systematic deviation of T_m values determined by DSC and FTIR spectroscopy. The aim of this paper is to explain this discrepancy by combined UV/Vis spectroscopic and MD computational approach. Multivariate analysis performed on temperature-dependent UV/Vis spectra of DPPE suspensions demonstrated that at 55 ± 1 °C certain phenomenon causes a small but detectable change in suspension turbidity, whereas a dominant change in the latter is registered at 63.2 ± 0.4 °C that coincides with T_m value determined from DSC curve. If this effect should be ignored, the overall data give T_m value the same as FTIR spectra data (61.0 ± 0.4 °C). As the classical MD simulations suggest that about 10° below T_m certain undulations appear at the surface of DPPE bilayers, we concluded that certain discontinuities in curvature fluctuations arise at reported temperature which are to some extent coupled with lipid melting. Ultimately, such events and the associated changes in curvature affect T_m value measured by different techniques.     

Circulating regulatory T cells are reduced in obesity and may identify subjects at increased metabolic and cardiovascular risk

Objective:

Reduced numbers of regulatory T (T_reg) cells have been observed in visceral adipose tissue of obese mice and humans. However, it is unknown whether human obesity affects circulating Treg cells and whether their number is associated with markers of systemic inflammation or glucose intolerance.

Design and Methods:

Peripheral blood mononuclear cells were isolated from venous blood of obese (BMI ≥ 27 kg/m²; n = 30) and nonobese (BMI ≥ 27 kg/m²; n = 13) individuals and analyzed using flow cytometry for the expression of CD4, CD25, and Foxp3.

Results:

Reduced circulating T_reg‐cell numbers were detected in obese compared with nonobese study participants (P = 0.038). Circulating CD4⁺CD25⁺CD127^?Foxp3 T_reg cells inversely correlated with body weight (P = 0.009), BMI (P = 0.004) and plasma leptin levels (P = 0.004) and were reduced in subjects with hsCRP ≥ 3.0 mg/L (P = 0.034) or HbA1c ≥ 5.5% (P < 0.005). Receiver operating characteristic curve analysis revealed a cutoff of circulating Treg cells < 1.06% to be predictive for hsCRP levels ≥ 3.0 mg/L, and logistic regression showed that the risk of having hsCRP levels ≥ 3.0 mg/L was increased 9.6‐fold (P = 0.008), if T_reg cells were below this threshold. The T_reg cutoff for HbA1c levels ≥ 5.5% was 0.73%, and this cutoff also predicted an increased risk of having elevated levels of both hsCRP and HbA1c, if only obese subjects were examined.

Conclusion:

Our findings thus reveal an association between circulating T_reg cells and measures of adiposity, inflammation, and glucose intolerance. Although further prospective studies are needed, we present data suggesting that the determination of T_reg cells might be useful to identify obese subjects at increased risk of developing cardiovascular and/or metabolic complications.

     

Texture analysis of cartilage T<Subscript>2</Subscript> maps: individuals with risk factors for OA have higher and more heterogeneous knee cartilage MR T<Subscript>2</Subscript> compared to normal controls - data from the osteoarthritis initiative

Introduction  

The goals of this study were (i) to compare the prevalence of focal knee abnormalities, the mean cartilage T₂ relaxation time, and the spatial distribution of cartilage magnetic resonance (MR) T₂ relaxation times between subjects with and without risk factors for Osteoarthritis (OA), (ii) to determine the relationship between MR cartilage T₂ parameters, age and cartilage morphology as determined with whole-organ magnetic resonance imaging scores (WORMS) and (iii) to assess the reproducibility of WORMS scoring and T₂ relaxation time measurements including the mean and grey level co-occurrence matrix (GLCM) texture parameters.     

High Dynamic Range Processing for Magnetic Resonance Imaging

Purpose

To minimize feature loss in T₁- and T₂-weighted MRI by merging multiple MR images acquired at different T_R and T_E to generate an image with increased dynamic range.

Materials and Methods

High Dynamic Range (HDR) processing techniques from the field of photography were applied to a series of acquired MR images. Specifically, a method to parameterize the algorithm for MRI data was developed and tested. T₁- and T₂-weighted images of a number of contrast agent phantoms and a live mouse were acquired with varying T_R and T_E parameters. The images were computationally merged to produce HDR-MR images. All acquisitions were performed on a 7.05 T Bruker PharmaScan with a multi-echo spin echo pulse sequence.

Results

HDR-MRI delineated bright and dark features that were either saturated or indistinguishable from background in standard T₁- and T₂-weighted MRI. The increased dynamic range preserved intensity gradation over a larger range of T₁ and T₂ in phantoms and revealed more anatomical features in vivo.

Conclusions

We have developed and tested a method to apply HDR processing to MR images. The increased dynamic range of HDR-MR images as compared to standard T₁- and T₂-weighted images minimizes feature loss caused by magnetization recovery or low SNR.     

7 Tesla Magnetic Resonance Imaging to Detect Cortical Pathology in Multiple Sclerosis

Background

Neocortical lesions (NLs) are an important pathological component of multiple sclerosis (MS), but their visualization by magnetic resonance imaging (MRI) remains challenging.

Objectives

We aimed at assessing the sensitivity of multi echo gradient echo (ME-GRE) T₂ ^*-weighted MRI at 7.0 Tesla in depicting NLs compared to myelin and iron staining.

Methods

Samples from two MS patients were imaged post mortem using a whole body 7T MRI scanner with a 24-channel receive-only array. Isotropic 200 micron resolution images with varying T₂ ^* weighting were reconstructed from the ME-GRE data and converted into R₂ ^* maps. Immunohistochemical staining for myelin (proteolipid protein, PLP) and diaminobenzidine-enhanced Turnbull blue staining for iron were performed.

Results

Prospective and retrospective sensitivities of MRI for the detection of NLs were 48% and 67% respectively. We observed MRI maps detecting only a small portion of 20 subpial NLs extending over large cortical areas on PLP stainings. No MRI signal changes suggestive of iron accumulation in NLs were observed. Conversely, R₂ ^* maps indicated iron loss in NLs, which was confirmed by histological quantification.

Conclusions

High-resolution post mortem imaging using R₂ ^* and magnitude maps permits detection of focal NLs. However, disclosing extensive subpial demyelination with MRI remains challenging.     

The control of CD4<Superscript>+</Superscript>CD25<Superscript>+</Superscript>Foxp3<Superscript>+</Superscript>regulatory T cell survival

   

CD4⁺CD25⁺Foxp3⁺ regulatory T (T_reg) cells are believed to play an important role in suppressing autoimmunity and maintaining peripheral tolerance. How their survival is regulated in the periphery is less clear. Here we show that T_reg cells express receptors for gamma chain cytokines and are dependent on an exogenous supply of these cytokines to overcome cytokine withdrawal apoptosis in vitro. This result was validated in vivo by the accumulation of T_reg cells in Bim^-/- and Bcl-2 tg mice which have arrested cytokine deprivation apoptosis. We also found that CD25 and Foxp3 expression were down-regulated in the absence of these cytokines. CD25⁺ cells from Scurfy mice do not depend on cytokines for survival demonstrating that Foxp3 increases their dependence on cytokines by suppressing cytokine production in T_reg cells. Our study reveals that the survival of T_reg cells is strictly dependent on cytokines and cytokine producing cells because they do not produce cytokines. Our study thus, demonstrates that different gamma chain cytokines regulate T_reg homeostasis in the periphery by differentially regulating survival and proliferation. These findings may shed light on ways to manipulate T_reg cells that could be utilized for their therapeutic applications.     

The effects of gradual or abrupt changes in salinity on digestive enzymes activity of Caspian kutum,Rutilus kutum (Kamensky, 1901) larvae

This study investigates the effects of gradual or abrupt changes in rearing salinity on food transit time and digestive enzymes activity of Caspian kutum (Rutilus kutum) larvae. The larvae (532 ± 0.05 mg) were supplied and randomly allocated into 12 tanks at a density of 45 fish per tank. Experimental treatments were fresh water (salinity 0) [FW] as control, exposure to salinity 5 [T₁], and gradual transfer to salinity 10 in two steps of first to 5 h, then and after 12 h to a salinity of 10 [T₂], and abrupt change (direct transfer to a salinity of 10 [T₃]). Results showed at 8 h after start of feeding that the larvae intestine was filled with food pellets except in treatment T₁. Enzyme activity responded to salinity change as follows: the highest trypsin, amylase, and chymotrypsin activities were observed in T₁; however, these were not significantly different to treatment T₃ (P > 0.05). Trypsin activity peaks in the FW and T₂ groups occurred 8 h after feeding, and in T₃ and T₁ groups 5 h after feeding. Peak chymotrypsin and alkaline phosphatase activity was observed 5 and 8 h after feeding in all experiments, respectively. The highest α amylase activity in FW and T₂ groups occurred 5 h after feeding, while in T₃ and T₁ these peaks were observed 8 h after feeding. These results indicate that salinity had some noticeable effects on the activities of digestive enzymes after feeding.     

Effect of Enhanced UV-B Radiation on Polyamine Content and Membrane Permeability in Cucumber Leaves

Cucumber plants (Cucumis sativus L., cv. Jingchun 3) were grown in a greenhouse under PAR illumination of 400–600 mol/(m² s) at 30/15°C (day/night) temperature. Two enhanced biologically effective UV-B radiation levels per day were applied: 8.82 kJ/m² (T₁) and 12.6 kJ/m² (T₂). Cucumber seedlings were irradiated 7 h per day for 25 days under T₁ and T₂. A comparative study of growth, membrane permeability, and polyamine content in cucumber leaves under T₁ and T₂ treatments was conducted. UV-B radiation resulted in the dose-dependent decrease in leaf area, dry weight of foliage, and plant height. The T₁ and T₂ treatments caused an increase in the contents of putrescine, spermine, and spermidine. However, the total polyamine content declined slightly when electrolyte leakage increased dramatically on the 18th day of treatment, especially after T₂ treatment. It can be concluded that polyamine accumulation in the cucumber leaves is an adaptive mechanism to the stress caused by UV-B radiation.     

Effects of age and leg length upon central loop of the Gastrocnemius-soleus H-reflex latency

Background  

central loop of the gastrocnemius-soleus H-reflex latency (T_c) that looks promising in the diagnosis of S1 radiculopathy; has been investigated in a few studies and only two of them have focused on the constitutional factors affecting it. Although leg length has been shown to contribute to the T_c, the role of age is controversial. More confusing, none of the previously performed studies have used strict criteria to rule out subclinical neuropathy, so the results could be misleading. This study has been performed to determine the influence of leg length and age on T_c among a carefully selected group of healthy volunteers.     

Subregional 6-[<Superscript>18</Superscript>F]fluoro-ʟ-<Emphasis Type="Italic">m</Emphasis>-tyrosine Uptake in the Striatum in Parkinson's Disease

Background  

In idiopathic Parkinson's disease (PD) the clinical features are heterogeneous and include different predominant symptoms. The aim of the present study was to determine the relationship between subregional aromatic l-amino acid decarboxylase (AADC) activity in the striatum and the cardinal motor symptoms of PD using high-resolution positron emission tomography (PET) with an AADC tracer, 6-[¹⁸F]fluoro-ʟ-m-tyrosine (FMT).     

Kernel based methods for accelerated failure time model with ultra-high dimensional data

Background  

Most genomic data have ultra-high dimensions with more than 10,000 genes (probes). Regularization methods with L ₁ and L _p penalty have been extensively studied in survival analysis with high-dimensional genomic data. However, when the sample size n ≪ m (the number of genes), directly identifying a small subset of genes from ultra-high (m > 10, 000) dimensional data is time-consuming and not computationally efficient. In current microarray analysis, what people really do is select a couple of thousands (or hundreds) of genes using univariate analysis or statistical tests, and then apply the LASSO-type penalty to further reduce the number of disease associated genes. This two-step procedure may introduce bias and inaccuracy and lead us to miss biologically important genes.     

Magnetic Resonance Water Proton Relaxation in Protein Solutions and Tissue: T1ρ Dispersion Characterization

Background

Image contrast in clinical MRI is often determined by differences in tissue water proton relaxation behavior. However, many aspects of water proton relaxation in complex biological media, such as protein solutions and tissue are not well understood, perhaps due to the limited empirical data.

Principal Findings

Water proton T₁, T₂, and T_1ρ of protein solutions and tissue were measured systematically under multiple conditions. Crosslinking or aggregation of protein decreased T₂ and T_1ρ, but did not change high-field T₁. T_1ρ dispersion profiles were similar for crosslinked protein solutions, myocardial tissue, and cartilage, and exhibited power law behavior with T_1ρ(0) values that closely approximated T₂. The T_1ρ dispersion of mobile protein solutions was flat above 5 kHz, but showed a steep curve below 5 kHz that was sensitive to changes in pH. The T_1ρ dispersion of crosslinked BSA and cartilage in DMSO solvent closely resembled that of water solvent above 5 kHz but showed decreased dispersion below 5 kHz.

Conclusions

Proton exchange is a minor pathway for tissue T₁ and T_1ρ relaxation above 5 kHz. Potential models for relaxation are discussed, however the same molecular mechanism appears to be responsible across 5 decades of frequencies from T_1ρ to T₁.     

Magnetic Resonance Evaluation of Multiple Myeloma at 3.0 Tesla: How Do Bone Marrow Plasma Cell Percentage and Selection of Protocols Affect Lesion Conspicuity?

Purpose

To compare various pulse sequences in terms of percent contrast and contrast-to-noise ratio (CNR) for detection of focal multiple myeloma lesions and to assess the dependence of lesion conspicuity on the bone marrow plasma cell percent (BMPC%).

Materials and Methods

Sagittal T₁-weighted FSE, fat-suppressed T₂-weighted FSE (FS- T₂ FSE), fast STIR and iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL) imaging of the lumbar spine were performed (n = 45). Bone marrow (BM)-focal myeloma lesion percent contrast and CNR were calculated. Spearman rank correlation coefficients were obtained between percent contrast, CNR and BMPC%. Percent contrasts and CNRs were compared among the three imaging sequences.

Results

BM-focal lesion percent contrasts, CNRs and BMPC% showed significant negative correlations in the three fat-suppression techniques. Percent contrast and CNRs were significantly higher for FS- T2 FSE than for STIR (P<0.01, P<0.05, respectively), but no significant differences were found among the three fat-suppression methods in the low tumor load BM group.

Conclusion

The higher BMPC% was within BM, the less conspicuous the focal lesion was on fat-suppressed MRI. The most effective protocol for detecting focal lesions was FS- T₂ FSE. In the high tumor load BM group, no significant differences in lesion conspicuity were identified among the three fat-suppression techniques.     

Effect of sand-stabilizing shrubs on soil respiration in a temperate desert

Aims

Explore how soil CO₂ efflux and its components change after moving sand dunes are stabilized with shrubs, and how abiotic factors affect those components at different scales.

Methods

Soil CO₂ efflux from a sand-stabilized area was compared to that from moving sand dunes in the Tengger Desert. To partition rhizosphere respiration (R_R) from soil basal respiration (R_B), a root-isolation plot was established.

Results

Compared to moving sand dunes, total soil respiration (R_T) in the sand-stabilized area increased 3.2 fold to 0.28?±?0.08 μmol CO₂ m^-2?s^-1, two thirds of which was from R_B. Shrub patchiness produced spatial variation in soil respiration, whereas temporal dynamics of soil respiration were affected mainly by soil water content. Shallow soil water content (0–20 cm) influenced R_T and R_B, whereas deep soil water content (30–210 cm) influenced R_R and the ratio R_R/R_T. During most of the year when soil water content was below field capacity, diurnal changes in soil respiration were partially decoupled from soil temperature but could be modeled using soil temperature and photosynthetic active radiation.

Conclusions

Sand-dune stabilization increased soil respiration, and increased R_B from biological soil crust and altered soil properties such as increased soil organic matter contributed more than increased R_R from increased shrubs.     

Effects of triiodothyronine on turnover rate and metabolizing enzymes for thyroxine in thyroidectomized rats

Aim

Previous studies in rats have indicated that surgical thyroidectomy represses turnover of serum thyroxine (T₄). However, the mechanism of this process has not been identified. To clarify the mechanism, we studied adaptive variation of metabolic enzymes involved in T₄ turnover.

Main methods

We compared serum T₄ turnover rates in thyroidectomized (Tx) rats with or without infusion of active thyroid hormone, triiodothyronine (T₃). Furthermore, the levels of mRNA expression and activity of the metabolizing enzymes, deiodinase type 1 (D1), type 2 (D2), uridine diphosphate-glucuronosyltransferase (UGT), and sulfotransferase were also compared in several tissues with or without T₃ infusion.

Key findings

After the T₃ infusion, the turnover rate of serum T₄ in Tx rats returned to normal. Although mRNA expression and activity of D1 decreased significantly in both liver and kidneys without T₃ infusion, D2 expression and activity increased markedly in the brain, brown adipose tissue, and skeletal muscle. Surprisingly, hepatic UGT mRNA expression and activity in Tx rats increased significantly in comparison with normal rats, and returned to normal after T₃ infusion.

Significance

This study suggests that repression of the disappearance of serum T₄ in rats after Tx is a homeostatic response to decreased serum T₃ concentrations. Additionally, T₄ glucuronide is a storage form of T₄, but may also have biological significance. These results suggest strongly that repression of deiodination of T₄ by D1 in the liver and kidneys plays a major role in thyroid hormone homeostasis in Tx rats, and that hepatic UGT also plays a key role in this mechanism.     

Effect of lamellarity and size on calorimetric phase transitions in single component phosphatidylcholine vesicles

Nano-differential scanning calorimetry (nano-DSC) is a powerful tool in the investigation of unilamellar (small unilamellar, SUVs, or large unilamellar, LUVs) vesicles, as well as lipids on supported bilayers, since it measures the main gel-to-liquid phase transition temperature (T_m), enthalpies and entropies. In order to assign these transitions in single component systems, where T_m often occurred as a doublet, nano-DSC, dynamic light scattering and cryo-transmission electron microscopy (cryo-TEM) data were compared. The two T_ms were not attributable to decoupled phase transitions between the two leaflets of the bilayer, i.e. nano-DSC measurements were not able to distinguish between the outer and inner leaflets of the vesicle bilayers. Instead, the two T_ms were attributed to mixtures of oligolamellar and unilamellar vesicles, as confirmed by cryo-TEM images. T_m for the oligolamellar vesicles was assigned to the peak closest to that of the parent multilamellar vesicle (MLV) peak. The other transition was higher than that of the parent MLVs for 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), and increased in temperature as the vesicle size decreased, while it was lower in temperature than that of the parent MLVs for 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), and decreased as the vesicle size decreased. These subtle shifts arose due to small differences in the values of ΔH and ΔS, since T_m is determined by their ratio (ΔH/ΔS). It was not possible to completely eliminate oligolamellar structures for MLVs extruded with the 200 nm pore size filter, even after 120 passes, while these structures were eliminated for MLVs extruded through the 50 nm pore size filter.