Loukas G. Astrakas

MRI evaluation of tissue iron burden in patients with β-thalassaemia major

Abstractβ-Thalassaemia major is a hereditary haemolytic anaemia that is treated with multiple blood transfusions. A major complication of this treatment is iron overload, which leads to cell death and organ dysfunction. Chelation therapy, used for iron elimination, requires effective monitoring of the body burden of iron, for which serum ferritin levels and liver iron content measured in liver biopsies are used as markers, but are not reliable. MRI based on iron-induced T2 relaxation enhancement can be used for the evaluation of tissue siderosis. Various MR protocols using signal intensity ratio and mainstream relaxometry methods have been used, sometimes with discrepant results. Relaxometry methods using multiple echoes achieve better sampling of the time domain in which relaxation mechanisms take place and lead to more precise results. In several studies the MRI parameters of liver siderosis have failed to correlate with those of other affected organs, underlining the necessity for MRI iron evaluation in individual organs. Most studies have included children in the evaluated population, but MRI data on very young children are lacking. Wider application of relaxometry methods is indicated, with the establishment of universally accepted MRI protocols, and further studies, including young children, are needed.

T2 relaxometry and fMRI of the brain in late-onset restless legs syndrome

Objective: To assess in patients with late-onset idiopathic restless legs syndrome (RLS) the brain iron content with magnetic resonance relaxometry, and brain activation during dorsiflexion and plantar flexion of both feet, using fMRI. Methods: The study was approved by the institutional review board, and informed consent was obtained. Twenty-five RLS patients (14 women, 11 men; age range 55–82 years; mean 66.5 ± 8.9 years; disease duration 6.5 ± 4.5 years) and 12 sex- and age-matched controls were studied. A T1-weighted high-resolution three-dimensional spoiled gradient echo sequence was used for structural imaging, a multislice spin echo Τ2-weighted sequence was used for T2 relaxometry, and a single-shot multislice gradient echo planar sequence was used for fMRI. The motor paradigm consisted of alternating periods of rest and movement, each 40 seconds in duration. Region of interest analysis was used on the T2 relaxometry maps. Statistical parametric mapping software was used for analysis of the functional data. Results: T2 relaxation time was significantly higher in patients than in controls in the substantia nigra pars compacta. Within-group analysis showed that both patients and controls activated the primary motor cortex, the primary somatosensory cortex, the somatosensory association cortex, and the middle cerebellar peduncles. Patients also activated the thalamus, putamen, middle frontal gyrus, and cingulate gyrus. Between-group analysis showed that patients had higher activation of the dorsolateral prefrontal cortex. Conclusion: Late-onset restless legs syndrome is associated with low iron content of the basal ganglia and increased activity of the dorsolateral prefrontal cortex. GLOSSARY: C = constant offset parameter added to compensate for background noise bias; CN = caudate nucleus; DMT1 = divalent metal transporter 1; DN = dentate nucleus; EPI = echo planar imaging; GP = globus pallidus; IRLS = International RLS Study Group Rating Scale; JHRLSS = Johns Hopkins RLS Severity Scale; MIP = maximum intensity projection; MR = magnetic resonance; PLMS = periodic limb movements in sleep; Pu = putamen; RLS = restless leg syndrome; RN = red nucleus; ROI = region of interest; SN = substantia nigra; SNc = substantia nigra pars compacta; SNr = substantia nigra pars reticulata; So = signal amplitude at echo time = 0; SPM = statistical parametric mapping; S(TE) = signal intensity at echo time; TE = echo time; Th = thalamus; TR = repetition time.

Age-related grey matter changes in preterm infants: An MRI study

Grey matter (GM) maturation has not been previously studied in healthy preterm children. The purpose of this study was to evaluate the age dependency of GM development in 116 GM areas in preterm subjects. Sixty one preterm infants (corrected age: 13.7+/-9.92 months, gestational age: 33.4+/-1.9 weeks) with normal structural appearance on MRI were included in the study. Using a T1-weighted high resolution 3D spoiled gradient echo sequence, volumes of 116 GM areas were calculated after their segmentation using the Voxel Based Morphometry Toolboxes and the Individual Brain Atlas Statistical Parametric Mapping (IBASPM) software packages. Non linear regression analysis assessed age dependency of volume data for every GM area using the monoexponential function y=A-Bexp(-x/C). All supratentorial GM areas followed the monoexponential function model reasonably well. Cerebellar structures had a poor goodness of fit. Volume increase of the individual GM areas followed an inferior to superior and a posterior to anterior pattern. The putamen, thalamus, and caudate nucleus reached 99% of the final volume earlier than most cortical GM areas. The visual cortex and the postcentral and precentral cortices matured earlier than the parietal, frontal and temporal cortices. The fronto-occipital asymmetry or torque seen in adults was observed in the preterm infants; the left occipital areas reached maturation earlier than the right, while the right prefrontal and frontal areas matured earlier than the left. To conclude, GM development progresses in a region-specific manner coinciding with functional, phylogenetical and regional white matter (WM) maturation.

Structural destabilization of chignolin under the influence of oscillating electric fields

The structural response of chignolin to 1 V/nm electric fields of different frequencies has been studied with molecular dynamics simulations and stochastic modeling. It was found that oscillating electric fields induce conformational changes to chignolin that are frequency dependent. For frequencies comparable with or smaller from the orientational self-diffusion rate, the peptide destabilizes after performing an oscillatory motion between the two possible directions of the electric field axis. For higher frequencies the field effects are averaged out and chignolin performs a Brownian rotation diffusion maintaining its native conformation. Stochastic modeling can describe chignolin’s oscillatory motion equally well with the molecular dynamics simulations. The time needed for these changes to take place has a stochastic nature depending, beyond frequency, on factors related with the hydrogen bonds’ stability and their geometrical arrangement in the structure.

A Sparse and Spatially Constrained Generative Regression Model for fMRI Data Analysis

In this study, we present an advanced Bayesian framework for the analysis of functional magnetic resonance imaging (fMRI) data that simultaneously employs both spatial and sparse properties. The basic building block of our method is the general linear regression model that constitutes a well-known probabilistic approach. By treating regression coefficients as random variables, we can apply an enhanced Gibbs distribution function that captures spatial constrains and at the same time allows sparse representation of fMRI time series. The proposed scheme is described as a maximum a posteriori approach, where the known expectation maximization algorithm is applied offering closed-form update equations for the model parameters. We have demonstrated that our method produces improved performance and functional activation detection capabilities in both simulated data and real applications.

Dynamic Contrast-Enhanced Subtraction MRI for Characterizing Intratesticular Mass Lesions

OBJECTIVE The objective of our study was to analyze the enhancement patterns of various intratesticular mass lesions at dynamic contrast-enhanced subtraction MRI and assess the value of the technique in distinguishing between benign and malignant lesions. MATERIALS AND METHODS We retrospectively evaluated the records and images of 44 consecutive men (11 benign and 16 malignant intratesticular lesions) who presented to the department of urology with a variety of clinical symptoms and were referred for imaging. Dynamic contrast-enhanced subtraction MRI was performed using a 3D fast-field echo sequence after the administration of paramagnetic contrast medium. Patients were divided into three groups according to the final diagnosis: benign intratesticular lesions, malignant intratesticular lesions, and normal testes. The patterns of contrast enhancement of both the normal testes and the intratesticular lesions were evaluated. Time-signal intensity plots were created and classified according to shape: Type I presented a linear increase of contrast enhancement throughout the examination, type II showed an initial upstroke followed by either a plateau or a gradual increase in the late contrast-enhanced phase, and type III presented an initial upstroke followed by gradual washout of the contrast medium. The relative percentages of peak height, maximum time, and mean slope were also calculated. RESULTS Normal testes enhanced homogeneously with a type I curve. Most benign intratesticular lesions showed inhomogeneous or homogeneous contrast enhancement and a type II curve. Testicular carcinomas showed heterogeneous contrast enhancement with a type III curve. The relative percentages of maximum time to peak proved the most important discriminating factor in differentiating malignant from benign intratesticular masses (p < 0.001). CONCLUSION Dynamic contrast-enhanced MRI may be used to distinguish between benign and malignant intratesticular mass lesions.

Shifting from region of interest (ROI) to voxel-based analysis in human brain mapping

Current clinical studies involve multidimensional high-resolution images containing an overwhelming amount of structural and functional information. The analysis of such a wealth of information is becoming increasingly difficult yet necessary in order to improve diagnosis, treatment and healthcare. Voxel-wise analysis is a class of modern methods of image processing in the medical field with increased popularity. It has replaced manual region of interest (ROI) analysis and has provided tools to make statistical inferences at voxel level. The introduction of voxel-based analysis software in all modern commercial scanners allows clinical use of these techniques. This review will explain the main principles, advantages and disadvantages behind these methods of image analysis.

Electric field effects on chignolin conformation

The effect of homogeneous and constant external electric fields on the structural stability of chignolin, a typical β-hairpin peptide, has been studied for 10ns using molecular dynamics simulations. The peptide aligns quickly its total dipole moment with the external electric field and then a constant stress is applied on its charged residues. For weaker fields this has mixed effects on the creation, destruction or strength of hydrogen bonds, but ultimately for strong fields chignolin unfolds starting by the separation of the terminal residues. Since the function of proteins is critically linked to their three-dimensional structures, these findings indicate that exposure to external electric fields may induce changes in conformation that can potentially initiate severe cellular dysfunction.

Voxel‐Based Morphometry and Voxel‐Based Relaxometry in Parkinsonian Variant of Multiple System Atrophy

Multiple system atrophy (MSA) is a progressive neurodegenerative disorder divided into a parkinsonian (MSA‐P) and a cerebellar variant. The purpose of this study was to assess regional brain atrophy and iron content using Voxel‐based morphometry (VBM) and Voxel‐based relaxometry (VBR) respectively, in MSA‐P.

Diffusion tensor and dynamic susceptibility contrast MRI in glioblastoma.

OBJECTIVE We prospectively investigated the correlation between diffusion tensor (DTI), dynamic susceptibility contrast (DSC) perfusion MRI metrics and Ki-67 labelling index in glioblastomas. METHODS We studied seventeen patients who were operated on for glioblastoma. DTI and DSC MRI were performed within a week prior to surgical excision. Lesion/normal ratios were calculated for the apparent diffusion coefficient (ADC), fractional anisotropy (FA), relative cerebral blood volume (rCBV), relative cerebral blood flow (rCBF) and relative mean transit time (rMTT) ratio. In the excised tumour specimens Ki-67 antigen expression was evaluated by the MIB-1 immunostaining method. RESULTS A significant correlation was observed between Ki-67 index and ADC ratio (r = -0.528, p = 0.029) and FA ratio (r = 0.589, p = 0.012). rCBV and rMTT presented a trend towards significant correlation with Ki-67 index (r = 0.628, p = 0.07 and r = 0.644, p = 0.06 respectively). There was a trend towards better survival for patients with gross total tumour excision and FA values lower than 0.48 (p = 0.1 and p = 0.09 respectively). No significant correlation was found between ADC ratio, rCBV, rCBF, rMTT and overall survival. CONCLUSION ADC ratio, FA ratio, rCBV and rMTT tumour/normal tissue ratios may represent indicators of glioma proliferation. FA values may hold promise for predicting survival in patients with glioblastoma.