Marko Daković

Brain iron MRI: A biomarker for amyotrophic lateral sclerosis

To evaluate the usefulness of MRI detection of hypointensity areas (iron deposits) in the brain using a dedicated MRI technique in patients with ALS in establishing this sign as a potential surrogate biomarker that correlates with the severity of disease.

Cortical thickness, surface area and folding in patients with psychogenic nonepileptic seizures

OBJECTIVE To determine cortical thickness (CTh), cortical surface area (CSA), curvature and sulcal depth (SD) in patients with psychogenic nonepileptic seizures (PNES). METHODS Freesurfer software was used to identify differences between active and control group in Cth, CSA, curvature, and SD. Neuropsychological tests intending to document possible frontal lobe deficit were applied. RESULTS We included 37 patients with PNES (age 37.3±13.8; female/male 31/6; age of disease onset 26.1±10.6; age of disease duration 11.1±11.1), and 37 healthy controls (age 38.4; ±12.7; female/male 26/11). No difference in CSA and curvature was detected between groups. Patients with PNES had increased CTh in the left insula, left and right medial-orbitofrontal, and left lateral-orbitofrontal, and decreased CTh in the left and right precentral, right enthorinal, and right lateral-occipital region than healthy controls. SD was increased at the level of the left and right insula, right rostral anterior cingulate, right posterior cingulate, and left cuneus, and reduced at the level of the right and left medial-orbitofrontal sulci in patients with PNES compared to healthy controls. CONCLUSION Individuals with PNES display a distinct profile of changes in CTh, in association with increase in SD in both insula as compared to controls. Our results may contribute to the understanding of the neurobiological background of PNES. Further research, to include replication of the findings and directed to understand the role of insula is needed.

Diffusion-weighted MRI versus transient elastography in quantification of liver fibrosis in patients with chronic cholestatic liver diseases

PURPOSE To evaluate the diagnostic value of diffusion-weighted magnetic resonance imaging (DWMRI) and transient elastography (TE) in quantification of liver fibrosis in patients with chronic cholestatic liver diseases. MATERIALS AND METHODS Forty-five patients underwent DWMRI, TE, and liver biopsy for staging of liver fibrosis. Apparent diffusion coefficient (ADC) was calculated for six locations in the liver for combination of five diffusion sensitivity values b=0, 50, 200, 400 and 800 s/mm(2). A receiver operating characteristic (ROC) analysis was performed to determine the diagnostic performance of DWMRI and TE. Segmental ADC variations were evaluated by means of coefficient of variation. RESULTS The mean ADCs (× 10(-3)mm(2)/s; b=0-800 s/mm(2)) were significantly different at stage F1 versus F ≥ 2 (p<0.05) and F2 versus F4. However, no significant difference was found between F2 and F3. For prediction of F ≥ 2 and F ≥ 3 areas under the ROC curves were 0.868 and 0.906 for DWMRI, and 0.966 and 0.960 for TE, respectively. The sensitivity and specificity were 90.9% and 89.3% for F ≥ 2 (ADC ≤ 1.65), and 92.3% and 92.1% for F ≥ 3 (ADC ≤ 1.63). Segmental ADC variation was lowest for F4 (CV=9.54 ± 6.3%). CONCLUSION DWMRI and TE could be used for assessment of liver fibrosis with TE having higher diagnostic accuracy and DWMRI providing insight into liver fibrosis distribution.

Profiling differences in chemical composition of brain structures using Raman spectroscopy.

Raman spectroscopy enables non-invasive investigation of chemical composition of biological tissues. Due to similar chemical composition, the analysis of Raman spectra of brain structures and assignment of their spectral features to chemical constituents presents a particular challenge. In this study we demonstrate that standard and independent component analysis of Raman spectra is capable of assessment of differences in chemical composition between functionally related gray and white matter structures. Our results show the ability of Raman spectroscopy to successfully depict variation in chemical composition between structurally similar and/or functionally connected brain structures. The observed differences were attributed to variations in content of proteins and lipids in these structures. Independent component analysis enabled separation of contributions of major constituents in spectra and revealed spectral signatures of low-concentration metabolites. This provided finding of discrepancies between structures of striatum as well as between white matter structures. Raman spectroscopy can provide information about variations in contents of major chemical constituents in brain structures, while the application of independent component analysis performed on obtained spectra can help in revealing minute differences between closely related brain structures.

On the mechanism of uranium binding to cell wall of Chara fragilis

Biosorption of uranium from nuclear waste liquids and contaminated surface waters and soils has recently attracted special interest. However, the detailed mechanism of uranium uptake by plants is not well understood. The aim of this work is to investigate the role of cell wall components of the freshwater alga Chara fragilis in uranium sequestration from its solution. Three types of algae preparations: extract of cell wall polysaccharides, dried and live algae were subjected to uranium solutions of different concentration and pH. FTIR and X-ray diffraction were used to assess both potential binding sites and the form of the uranyl sequestered by algae. Sorption of uranium by live and dry algae shows remarkable differences both in terms of overall uptake and mechanisms involved. All experiments are consistent with the conclusion that coprecipitation of uranyl species with CaCO3 is the major binding mechanism in uranium sequestration by Chara fragilis, while the direct exchange of Ca2+ with UO22+ has a minor role. Live algae are twice as efficient in sequestering uranium from solution than dried ones due to the formation of different crystalline forms such as aragonite and rutherfordine forming in live algae in the presence of the uranyl species in solution. It therefore appears that metabolic processes such as photosynthesis, most likely through the regulation of pH, play a key role in the uranium uptake by plants. Further understanding of the complex mechanism of metabolic control of the uranium uptake by plants is needed before the planning of bioremediation of this element.

Proton magnetic resonance spectroscopy of the intrinsic tongue muscles in patients with myasthenia gravis with different autoantibodies

OBJECTIVE To assess lipid composition of the intrinsic tongue muscles in patients with myasthenia gravis (MG). METHODS This study included 15 MG patients with antibodies against muscle-specific kinase (MuSK), 15 matched MG patients with antibodies against acetylcholine receptor (AChR) and 15 matched healthy subjects. Middle posterior region of the tongue was analyzed by single voxel point-resolved proton magnetic resonance spectroscopy (MRS) using 1.5T MRI scanner. RESULTS MRS obtained from subject with AChR MG showed a broad resonance arising from methylene groups of lipids (PMN) with no observable shoulder attributed to methyl groups (PML). Full-width at half maximum (FWHM) of PMN+PML peak showed higher value in patients with AChR MG in comparison to healthy subjects and MuSK MG patients (p<0.05). In patients with MuSK MG, the shape and FWHM of PMN+PML peak was similar as in healthy subjects (p>0.05), with tendency toward increased ratio between PMN and resonance from vinyl protons of lipids (PV). In both AChR and MuSK MG, total creatine resonance (creatine+phosphocreatine, CP) was almost absent with significant increase of PMN/CP ratio in comparison to healthy subjects (p<0.05). CONCLUSION MRS is useful in revealing muscle lipid composition in MG. In patients with AChR MG, MRS showed increased lipid content in the tongue muscles due to the lipid migration from intra- to extramyocellular space. Finding in patients with MuSK MG might reflect intramyocellular lipid deposition in the tongue. CP decrease in tongue muscles indicated impairment of oxidative metabolism in both AChR MG and MuSK MG.

Changes of the peripheral blood mononuclear cells membrane fluidity from type 1 Gaucher disease patients: an electron paramagnetic resonance study

Abstract Gaucher disease (GD) is a lysosomal storage disorder, caused by an impaired function of β-glucocerebrosidase, which results in accumulation of glucocerebroside in cells, and altered membrane ordering. Using electron paramagnetic resonance spin labeling, a statistically significant difference in the order parameter between the peripheral blood mononuclear cell membranes of GD patients and healthy controls was observed. Moreover, the results show that the introduction of the enzyme replacement therapy leads to the restoration of the physiological membrane fluidity. Accordingly, this simple method could serve as a preliminary test for GD diagnosis and therapy efficiency.

THE PARAMAGNETIC PILLARED BENTONITES AS DIGESTIVE TRACT MRI CONTRAST AGENTS

The increased use of imaging techniques in diagnostic studies, such as MRI, has contributed to the development of the wide range of new materials which could be successfully used as image improving agents. However, there is a lack of such substances in the area of gastrointestinal tract MRI. Many of the traditionally popular relaxation altering agents show poor results and disadvantages provoking black bowel, side effects of diarrhea and the presence of artifacts arising from clumping. Paramagnetic species seem to be potentially suitable agents for these studies, but contrast opacification has been reported and less than 60% of the gastrointestinal tract magnetic resonance scans showed improved delineation of abdominal pathologies. The new solution has been proposed as zeolites or smectite clays (hectorite and montmorillonite) enclosing of paramagnetic metal ions obtained by ion-exchange methods. However, such materials have problems of leakage of paramagnetic ions causing the appearance of the various side-effects. In this study we show that Co+2 and Dy+3 paramagnetic-pillared bentonites could be successfully used as MRI digestive tract non-leaching contrast agents, altering the longitudinal and transverse relaxation times of fluids in contact with the clay minerals.

Binding of p-mercaptobenzoic acid and adenine to gold-coated electroless etched silicon nanowires studied by surface-enhanced Raman scattering

Modern diagnostic tools ever aim to reduce the amount of analyte and the time needed for obtaining the result. Surface-enhanced Raman spectroscopy is a method that could satisfy both of these requirements, provided that for each analyte an adequate substrate is found. Here we demonstrate the ability of gold-sputtered silicon nanowires (SiNW) to bind p-mercaptobenzoic acid in 10-3, 10-4 and 10-5M and adenine in 30 and 100μM concentrations. Based on the normal mode analysis, presented here for the first time, the binding of p-mercaptobenzoic acid is deduced. The intensity enhancement of the 1106cm-1 band is explained by involvement of the CS stretching deformation, and the appearance of the broad 300cm-1 band attributed to SAu stretching mode. Adenine SERS spectra demonstrate the existence of the 7H tautomer since the strongest band observed is at 736cm-1. The adenine binding is likely to occur in several ways, because the number of observed bands in the 1200-1600cm-1 interval exceeds the number of observed bands in the normal Raman spectrum of the free molecule.

Migraine with Aura: Surface-Based Analysis of the Cerebral Cortex with Magnetic Resonance Imaging

Objective Previous migraine studies have reported gray matter alterations in various cortical regions with conflicting results. This study aimed to explore a cortical morphometric difference in migraineurs with aura (MA) compared to healthy subjects (HS) and to delineate a possible difference between the cortical morphological features and different aura phenotypes. Materials and Methods Forty-eight MA and 30 HS that were balanced by sex, age, and educational level were selected for this study. T2-weighted and three-dimensional T1-weighted magnetic resonance imaging (MRI) of the brain were acquired using a 1.5T MRI scanner. Surface-based morphometry from the MRI data was used to identify differences between the MA and HS group, and then between MA subgroups. The MA group was subdivided into migraineurs who experienced only visual aura (MVA) and migraineurs who had visual, somatosensory and dysphasic symptoms (MVA+). Results The MVA+ group had significantly reduced cortical surface area of the left rostral middle frontal cortex compared with the MVA group (p < 0.001). Migraine patients had significantly reduced volume of the left fusiform gyrus relative to HS (p < 0.001). Also, the sulcal depth increased at the level of the left temporal pole in the MVA+ group relative to the MVA group (p < 0.001). The vertex-by-vertex analysis did not exhibit any significant difference in cortical thickness between MA and HS, and between MVA+ and MVA, when corrected for multiple comparisons. Conclusion Migraineurs with aura demonstrates different morphometric features from HS in multiple cortical regions. MVA+ have different morphometric features in the left frontal and temporal lobe relative to MVA, which could be a source of distinct symptoms and serve as potential biomarkers of different MA subtypes.