An In Vitro Study of the Intervertebral Disc Structure Using 3 T Magnetic Resonance Imaging

Study Design. An in vitro magnetic resonance imaging (MRI) study. Objective. Investigate the potential of high-field MRI for producing higher quality images of the intervertebral disc (IVD) to better distinguish structural details. Summary of Background Data. Higher spatial and contrast resolution are important advantages when imaging the complex tissue structures in the spine such as the IVDs. However, at present it is challenging to capture the substructural details in the IVD such as the lamellae. Methods. Three MRI sequences; two-dimensional proton-density-weighted Turbo-Spin-Echo (PD-TSE), 2D T2-weighted Turbo-Spin-Echo (T2W-TSE) with fat-saturation (FS), and 3D Spoiled-Gradient-Echo (3D-GE), were modified based on the image quality and scan duration. IVDs of three intact cadaveric lumbar-spines (T12–S1, Age 83–94 yr) were imaged using these optimized sequences. Thereafter each IVD was transversely sectioned and the exposed surfaces were photographed. Landmark observations from corresponding MRI slices and photographs were compared to confirm the MRI captured morphology. The image quality was evaluated using signal-to-noise ratio (SNR), and relative-contrast values. Finally, the underlying tissue structures, including specific pathological features, were qualitatively compared between the MR images and photographs. Results. Observations from photographs and corresponding MRI slices matched well. The PD-TSE sequence had better overall SNR, but the relative contrast between the tissue types was relatively poor. The 3D-GE sequence had higher relative contrast between the IVD and bone, but not between annulus and nucleus regions. The T2W images provided the best relative contrast between the annulus and nucleus, however the standard deviations here were high. Structural details including fissures, vascular and granular tissue proliferation, and pathologies in the endplate region, were identifiable from the MR images obtained using the optimized sequences. Conclusion. The results demonstrate the potential of high-field MRI to capture the IVD structural details. Since the acquisition durations were within clinically acceptable levels, these methodological improvements have the potential to enhance clinical diagnostics

The effect of ageing on skeletal muscle as assessed by quantitative MR imaging: an association with frailty and muscle strength

Background: Skeletal muscles undergo changes with ageing which can cause sarcopenia that can result in frailty. Quantitative MRI may detect the muscle-deficit component of frailty which could help improve the understanding of ageing muscles. Aims: To investigate whether quantitative MRI measures of T2, fat fraction (FF), diffusion tensor imaging and muscle volume can detect differences within the muscles between three age groups, and to assess how these measures compare with frailty index, gait speed and muscle power. Methods: 18 ‘young’ (18–30 years), 18 ‘middle-aged’ (31–68 years) and 18 ‘older’ (> 69 years) healthy participants were recruited. Participants had an MRI of their dominant thigh. Knee extension and flexion power and handgrip strength were measured. Frailty (English Longitudinal Study of Ageing frailty index) and gait speed were measured in the older participants. Results: Young participants had a lower muscle MRI T2, FF and mean diffusivity than middle-aged and older participants; middle-aged participants had lower values than older participants. Young participants had greater muscle flexion and extension power, muscle volume and stronger hand grip than middle-aged and older participants; middle-aged participants had greater values than the older participants. Quantitative MRI measurements correlated with frailty index, gait speed, grip strength and muscle power. Discussion: Quantitative MRI and strength measurements can detect muscle differences due to ageing. Older participants had raised T2, FF and mean diffusivity and lower muscle volume, grip strength and muscle power. Conclusions: Quantitative MRI measurements correlate with frailty and muscle function and could be used for identifying differences across age groups within muscle

Normal values and test–retest variability of stimulated-echo diffusion tensor imaging and fat fraction measurements in the muscle

OBJECTIVES: To assess the test–retest variability of both diffusion parameters and fat fraction (FF) estimates in normal muscle, and to assess differences in normal values between muscles in the thigh. METHODS: 29 healthy volunteers (mean age 37 years, range 20–60 years, 17/29 males) completed the study. Magnetic resonance images of the mid-thigh were acquired using a stimulated echo acquisition mode-echoplanar imaging (STEAM-EPI) imaging sequence, to assess diffusion, and 2-point Dixon imaging, to assess FF. Imaging was repeated in 19 participants after a 30 min interval in order to assess test–retest variability of the measurements. RESULTS: Intraclass correlation coefficients (ICCs) for test–retest variability were 0.99 [95% confidence interval, (CI): 0.98, 1] for FF, 0.94 (95% CI: 0.84, 0.97) for mean diffusivity and 0.89 (95% CI: 0.74, 0.96) for fractional anisotropy (FA). FF was higher in the hamstrings than the quadriceps by a mean difference of 1.81% (95% CI:1.63, 2.00)%, p < 0.001. Mean diffusivity was significantly lower in the hamstrings than the quadriceps (0.26 (0.13, 0.39) x10- 3 mm2s−1, p < 0.001) whereas fractional anisotropy was significantly higher in the hamstrings relative to the quadriceps with a mean difference of 0.063 (0.05, 0.07), p < 0.001. CONCLUSIONS: This study has shown excellent test-retest, variability in MR-based FF and diffusion measurements and demonstrated significant differences in these measures between hamstrings and quadriceps in the healthy thigh. ADVANCES IN KNOWLEDGE: Test–retest variability is excellent for STEAM-EPI diffusion and 2-point Dixon-based FF measurements in the healthy muscle. Inter- and intraobserver variability were excellent for region of interest placement for STEAM-EPI diffusion and 2-point Dixon-based FF measurements in the healthy muscle. There are significant differences in FF and diffusion measurements between the hamstrings and quadriceps in the normal muscle

Diffusion Tensor Imaging for Diagnosing Root Avulsions in Traumatic Adult Brachial Plexus Injuries: A Proof-of-Concept Study

Cross-sectional MRI has modest diagnostic accuracy for diagnosing traumatic brachial plexus root avulsions. Consequently, patients either undergo major exploratory surgery or months of surveillance to determine if and what nerve reconstruction is needed. This study aimed to develop a diffusion tensor imaging (DTI) protocol at 3 Tesla to visualize normal roots and identify traumatic root avulsions of the brachial plexus. Seven healthy adults and 12 adults with known (operatively explored) unilateral traumatic brachial plexus root avulsions were scanned. DTI was acquired using a single-shot echo-planar imaging sequence at 3 Tesla. The brachial plexus was visualized by deterministic tractography. Fractional anisotropy (FA) and mean diffusivity (MD) were calculated for injured and avulsed roots in the lateral recesses of the vertebral foramen. Compared to healthy nerves roots, the FA of avulsed nerve roots was lower (mean difference 0.1 [95% CI 0.07, 0.13]; p < 0.001) and the MD was greater (mean difference 0.32 × 10−3 mm2/s [95% CI 0.11, 0.53]; p < 0.001). Deterministic tractography reconstructed both normal roots and root avulsions of the brachial plexus; the negative-predictive value for at least one root avulsion was 100% (95% CI 78, 100). Therefore, DTI might help visualize both normal and injured roots of the brachial plexus aided by tractography. The precision of this technique and how it relates to neural microstructure will be further investigated in a prospective diagnostic accuracy study of patients with acute brachial plexus injuries

MRI in acute muscle tears in athletes: can quantitative T2 and DTI predict return to play better than visual assessment?

Objectives To assess the ability of quantitative T2, diffusion tensor imaging (DTI) and radiologist’s scores to detect muscle changes following acute muscle tear in soccer and rugby players. To assess the ability of these parameters to predict return to play times. Methods In this prospective, longitudinal study, 13 male athletes (age 19 to 34 years; mean 25 years) underwent MRI within 1 week of suffering acute muscle tear. Imaging included measurements of T2 and DTI parameters. Images were also assessed using modified Peetrons and British athletics muscle injury classification (BAMIC) scores. Participants returned for a second scan within 1 week of being determined fit to return to play. MRI measurements were compared between visits. Pearson’s correlation between visit 1 measurements and return to play times was assessed. Results There were significant differences between visits in BAMIC scores (Z = − 2.088; p = 0.037), modified Peetrons (Z = − 2.530; p = 0.011) and quantitative MRI measurements; T2, 13.12 ms (95% CI, 4.82 ms, 21.42 ms; p = 0.01); mean diffusivity (0.22 (0.04, 0.39); p = 0.02) and fractional anisotropy (0.07 (0.01, 0.14); p = 0.03). BAMIC scores showed a significant correlation with return to play time (Rs = 0.64; p = 0.02), but modified Peetrons scores and quantitative parameters did not. Conclusions T2 and DTI measurements in muscle can detect changes due to healing following muscle tear. Although BAMIC scores correlated well with return to play times, in this small study, quantitative MRI values did not, suggesting that T2 and DTI measurements are inferior predictors of return to play time compared with visual scoring. Key Points • Muscle changes following acute muscle tear can be measured using T2 and diffusion measurements on MRI. • Measurements of T2 and diffusion using MRI are not as good as a radiologist’s visual report at predicting return to play time after acute muscle tear

The efficacy of iron chelator regimes in reducing cardiac and hepatic iron in patients with thalassaemia major: a clinical observational study

<p>Abstract</p> <p>Background</p> <p>Available iron chelation regimes in thalassaemia may achieve different changes in cardiac and hepatic iron as assessed by MR. The aim of this study was to assess the efficacy of four available iron chelator regimes in 232 thalassaemia major patients by assessing the rate of change in repeated measurements of cardiac and hepatic MR.</p> <p>Results</p> <p>For the heart, deferiprone and the combination of deferiprone and deferoxamine significantly reduced cardiac iron at all levels of iron loading. As patients were on deferasirox for a shorter time, a second analysis ("Initial interval analysis") assessing the change between the first two recorded MR results for both cardiac and hepatic iron (minimum interval 12 months) was made. Combination therapy achieved the most rapid fall in cardiac iron load at all levels and deferiprone alone was significantly effective with moderate and mild iron load. In the liver, deferasirox effected significant falls in iron load and combination therapy resulted in the most rapid decline.</p> <p>Conclusion</p> <p>With the knowledge of the efficacy of the different available regimes and the specific iron load in the heart and the liver, appropriate tailoring of chelation therapy should allow clearance of iron. Combination therapy is best in reducing both cardiac and hepatic iron, while monotherapy with deferiprone or deferasirox are effective in the heart and liver respectively. The outcomes of this study may be useful to physicians as to the chelation they should prescribe according to the levels of iron load found in the heart and liver by MR.</p

A Secular Trend toward Earlier Male Sexual Maturity: Evidence from Shifting Ages of Male Young Adult Mortality

This paper shows new evidence of a steady long-term decline in age of male sexual maturity since at least the mid-eighteenth century. A method for measuring the timing of male maturity is developed based on the age at which male young adult mortality accelerates. The method is applied to mortality data from Sweden, Denmark, Norway, the United Kingdom, and Italy. The secular trend toward earlier male sexual maturity parallels the trend toward earlier menarche for females, suggesting that common environmental cues influence the speed of both males' and females' sexual maturation

Proteomic analysis of the Plasmodium male gamete reveals the key role for glycolysis in flagellar motility.

BACKGROUND: Gametogenesis and fertilization play crucial roles in malaria transmission. While male gametes are thought to be amongst the simplest eukaryotic cells and are proven targets of transmission blocking immunity, little is known about their molecular organization. For example, the pathway of energy metabolism that power motility, a feature that facilitates gamete encounter and fertilization, is unknown. METHODS: Plasmodium berghei microgametes were purified and analysed by whole-cell proteomic analysis for the first time. Data are available via ProteomeXchange with identifier PXD001163. RESULTS: 615 proteins were recovered, they included all male gamete proteins described thus far. Amongst them were the 11 enzymes of the glycolytic pathway. The hexose transporter was localized to the gamete plasma membrane and it was shown that microgamete motility can be suppressed effectively by inhibitors of this transporter and of the glycolytic pathway. CONCLUSIONS: This study describes the first whole-cell proteomic analysis of the malaria male gamete. It identifies glycolysis as the likely exclusive source of energy for flagellar beat, and provides new insights in original features of Plasmodium flagellar organization

Identification of alternative splice variants in Aspergillus flavus through comparison of multiple tandem MS search algorithms

<p>Abstract</p> <p>Background</p> <p>Database searching is the most frequently used approach for automated peptide assignment and protein inference of tandem mass spectra. The results, however, depend on the sequences in target databases and on search algorithms. Recently by using an alternative splicing database, we identified more proteins than with the annotated proteins in <it>Aspergillus flavus</it>. In this study, we aimed at finding a greater number of eligible splice variants based on newly available transcript sequences and the latest genome annotation. The improved database was then used to compare four search algorithms: Mascot, OMSSA, X! Tandem, and InsPecT.</p> <p>Results</p> <p>The updated alternative splicing database predicted 15833 putative protein variants, 61% more than the previous results. There was transcript evidence for 50% of the updated genes compared to the previous 35% coverage. Database searches were conducted using the same set of spectral data, search parameters, and protein database but with different algorithms. The false discovery rates of the peptide-spectrum matches were estimated < 2%. The numbers of the total identified proteins varied from 765 to 867 between algorithms. Whereas 42% (1651/3891) of peptide assignments were unanimous, the comparison showed that 51% (568/1114) of the RefSeq proteins and 15% (11/72) of the putative splice variants were inferred by all algorithms. 12 plausible isoforms were discovered by focusing on the consensus peptides which were detected by at least three different algorithms. The analysis found different conserved domains in two putative isoforms of UDP-galactose 4-epimerase.</p> <p>Conclusions</p> <p>We were able to detect dozens of new peptides using the improved alternative splicing database with the recently updated annotation of the <it>A. flavus </it>genome. Unlike the identifications of the peptides and the RefSeq proteins, large variations existed between the putative splice variants identified by different algorithms. 12 candidates of putative isoforms were reported based on the consensus peptide-spectrum matches. This suggests that applications of multiple search engines effectively reduced the possible false positive results and validated the protein identifications from tandem mass spectra using an alternative splicing database.</p

Tear fluid biomarkers in ocular and systemic disease: potential use for predictive, preventive and personalised medicine

In the field of predictive, preventive and personalised medicine, researchers are keen to identify novel and reliable ways to predict and diagnose disease, as well as to monitor patient response to therapeutic agents. In the last decade alone, the sensitivity of profiling technologies has undergone huge improvements in detection sensitivity, thus allowing quantification of minute samples, for example body fluids that were previously difficult to assay. As a consequence, there has been a huge increase in tear fluid investigation, predominantly in the field of ocular surface disease. As tears are a more accessible and less complex body fluid (than serum or plasma) and sampling is much less invasive, research is starting to focus on how disease processes affect the proteomic, lipidomic and metabolomic composition of the tear film. By determining compositional changes to tear profiles, crucial pathways in disease progression may be identified, allowing for more predictive and personalised therapy of the individual. This article will provide an overview of the various putative tear fluid biomarkers that have been identified to date, ranging from ocular surface disease and retinopathies to cancer and multiple sclerosis. Putative tear fluid biomarkers of ocular disorders, as well as the more recent field of systemic disease biomarkers, will be shown