Gyula Kotek - Academia.edu (original) (raw)

Papers by Gyula Kotek

Research paper thumbnail of Image registration improves human knee cartilage T1 mapping with delayed gadolinium-enhanced MRI of cartilage (dGEMRIC)

European Radiology, 2012

Objectives To evaluate the effect of automated registration in delayed gadolinium-enhanced MRI of... more Objectives To evaluate the effect of automated registration in delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) of the knee on the occurrence of movement artefacts on the T1 map and the reproducibility of region-of-interest (ROI)-based measurements. Methods Eleven patients with early-stage knee osteoarthritis and ten healthy controls underwent dGEMRIC twice at 3T. Controls underwent unenhanced imaging. ROIs were manually drawn on the femoral and tibial cartilage. T1 calculation was performed with and without registration of the T1weighted images. Automated three-dimensional rigid registration was performed on the femur and tibia cartilage separately. Registration quality was evaluated using the square root Cramér-Rao lower bound (CRLB σ). Additionally, the reproducibility of dGEMRIC was assessed by comparing automated registration with manual slice-matching. Results Automated registration of the T1-weighted images improved the T1 maps as the 90% percentile of the CRLB σ was significantly (P<0.05) reduced with a median reduction of 55.8 ms (patients) and 112.9 ms (controls). Manual matching and automated registration of the re-imaged T1 map gave comparable intraclass correlation coefficients of respectively 0.89/0.90 (patients) and 0.85/0.85 (controls). Conclusions Registration in dGEMRIC reduces movement artefacts on T1 maps and provides a good alternative to manual slice-matching in longitudinal studies. Key Points • Quantitative MRI is increasingly used for biomedical assessment of knee articular cartilage • Image registration leads to more accurate quantification of cartilage quality and damage • Movement artefacts in delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) are reduced • Automated image registration successfully aligns baseline and follow-up dGEMRIC examinations • Reproducibility of dGEMRIC with registration is similar to that using manual slice-matching

Research paper thumbnail of From signal-based to comprehensive magnetic resonance imaging

Scientific Reports

We present and evaluate a new insight into magnetic resonance imaging (MRI). It is based on the a... more We present and evaluate a new insight into magnetic resonance imaging (MRI). It is based on the algebraic description of the magnetization during the transient response—including intrinsic magnetic resonance parameters such as longitudinal and transverse relaxation times (T1, T2) and proton density (PD) and experimental conditions such as radiofrequency field (B1) and constant/homogeneous magnetic field (B0) from associated scanners. We exploit the correspondence among three different elements: the signal evolution as a result of a repetitive sequence of blocks of radiofrequency excitation pulses and encoding gradients, the continuous Bloch equations and the mathematical description of a sequence as a linear system. This approach simultaneously provides, in a single measurement, all quantitative parameters of interest as well as associated system imperfections. Finally, we demonstrate the in-vivo applicability of the new concept on a clinical MRI scanner.

Research paper thumbnail of Atrophy and decreased activation of fronto-parietal attention areas contribute to higher visual dysfunction in posterior cortical atrophy

Psychiatry Research: Neuroimaging, 2008

Voxel-based morphometry and functional magnetic resonance imaging demonstrated severe atrophy and... more Voxel-based morphometry and functional magnetic resonance imaging demonstrated severe atrophy and decreased activation of visual attention areas and occipital lobes in a patient with early posterior cortical atrophy compared with healthy controls and patients with early Alzheimer&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease. Our complex approach indicates that structures responsible for attention can be damaged early in posterior cortical atrophy and may contribute to the characteristic decline in higher visual functions.

Research paper thumbnail of 163 CELL TRACKING FOR CARTILAGE REPAIR USING SUPERPARAMAGNETIC IRON OXIDES: CLINICAL POTENTIAL

Osteoarthritis and Cartilage, 2010

maintain the mature chondrocyte phenotype avoiding terminal differentiation towards hypertrophy r... more maintain the mature chondrocyte phenotype avoiding terminal differentiation towards hypertrophy represents a major issue and is the objective of this study. Methods: Bone marrow-derived murine MSCs were induced to differentiate towards chondrocytes using the micropellet culture technique in presence of Wnt-6 containing conditioned medium (CM). CM was obtained after incubation of a chondrogenic medium consisting of DMEM supplemented with ITS, proline, ascorbic acid and sodium pyruvate for 48h on confluent NIH-3T3 cells stably transfected to secrete Wnt-6. As controls, CM from NIH-3T3 cells or BMP-2 containing medium was used. Similar conditions were used to obtain CM with osteogenic or adipogenic media. After 21 days, quantitative RT-PCR was performed on total RNA to detect the expression of markers specific for each lineage and staining specific for proteoglycans, mineralization or lipid droplets was performed. Western blotting with antiβ-catenin, anti-JNK or anti-PKC antibodies was performed after migration and transfer on nitrocellulose membranes of 20 μg total proteins extracted from pellets after a time course exposure to the different CM. Results: Pellet culture of murine MSCs in presence of NIH-derived CM or chondrogenic medium alone did not up-regulate the chondrocytic markers. On the contrary, Wnt-6 containing CM was sufficient to induce the differentiation of MSCs into chondrocytes as shown by the induction of collagen type IIB, aggrecan and COMP and a positive staining for proteoglycans. The expression levels of the transcripts were lower than those induced by BMP-2. However, contrary to BMP-2, we observed the lack of induction of the hypertrophic markers collagen type X and alkaline phosphatase when MSCs were cultured in Wnt-6 CM. Interestingly, in osteogenic or adipogenic conditions, MSCs did not up-regulate the markers specific for osteoblasts or adipocytes and rather decreased their expression level. The up-regulation of chondrocytic markers by Wnt-6 was associated with a lack of induction of the β-catenin or JNK pathways and preliminary results suggest that PKC signalling may be induced. Conclusions: Our results suggest that Wnt-6 is one new chondrogenic factor sufficient to specifically induce the generation of chondrocytes and inhibiting their terminal differentiation. Preliminary results suggest that Wnt-6 might induce the PKC-dependent pathway to activate the chondrocyte-specific genes.

Research paper thumbnail of Clinically Translatable Cell Tracking and Quantification by MRI in Cartilage Repair Using Superparamagnetic Iron Oxides

PLOS One, 2011

Background: Articular cartilage has very limited intrinsic regenerative capacity, making cell-bas... more Background: Articular cartilage has very limited intrinsic regenerative capacity, making cell-based therapy a tempting approach for cartilage repair. Cell tracking can be a major step towards unraveling and improving the repair process of these therapies. We studied superparamagnetic iron oxides (SPIO) for labeling human bone marrow-derived mesenchymal stem cells (hBMSCs) regarding effectivity, cell viability, long term metabolic cell activity, chondrogenic differentiation and hBMSC secretion profile. We additionally examined the capacity of synovial cells to endocytose SPIO from dead, labeled cells, together with the use of magnetic resonance imaging (MRI) for intra-articular visualization and quantification of SPIO labeled cells.

Research paper thumbnail of Der Einfluss der Fütterung auf die Zusammensetzung verschiedener Fettdepots von Jungbullen der Rassen Ungarisches Grauvieh und Holstein Friesian 2. Mitteilung: 1 H- Nuclear Magnetic Resonance (NMR) Untersuchungen

In this attempt the relaxation times using 1 H-NMR spectroscopy from three different (subcutaneou... more In this attempt the relaxation times using 1 H-NMR spectroscopy from three different (subcutaneous, perinephric and internal fat) fat depots of Hungarian Grey and Holstein Friesian extensive or intensive fattened young bulls were measured. The relaxation properties were compared with the analysis of fatty acid compostion. The different diets and the sample location have a higher influence on the relaxation times than the breed. In fat samples from extensive groups the T 1 -relaxation time was longer, while the T 2 -relaxation time was significantly shorter in intensive fed groups. The T 2 -relaxation time, as well as the relaxation time of T 21 -und T 22 -components were the shortest in extensive fed animals, while the proportion of T 21 -component was the highest in kidney fat, furthermore the difference was statistics proved. The T 2 -relaxation time showed a close negative relationship with the ratio of saturated fatty acids (SFA). The ratio of v 21 and v 22 depends on chemical composition of fat samples. In fat tissues with a high SFA percentage caused a higher proportion of v 21 . It is suggested that differences in fatty acid compositon of fat samples caused also alteration in the relaxation time.

Research paper thumbnail of In vivo brain edema classification: New insight offered by large b-value diffusion-weighted MR imaging

Journal of Magnetic Resonance Imaging, 2007

PurposeTo assess the role of large b-value diffusion weighted imaging (DWI) in the characterizati... more PurposeTo assess the role of large b-value diffusion weighted imaging (DWI) in the characterization of the physicochemical properties of the water in brain edema under experimental and clinical conditions.To assess the role of large b-value diffusion weighted imaging (DWI) in the characterization of the physicochemical properties of the water in brain edema under experimental and clinical conditions.Materials and MethodsVasogenic brain edema was induced in mice by means of cold injury. A total of 17 patients with extensive peritumoral brain edema were also investigated. The longitudinal relaxation time (T1) and apparent diffusion coefficient (D) were measured in the edematous area both in humans and in mice. D was calculated by using both mono- (Dmono) and biexponential (Dfast and Dslow) approaches in the low and overall range of b-values, respectively. The D values were correlated with the T1 values.Vasogenic brain edema was induced in mice by means of cold injury. A total of 17 patients with extensive peritumoral brain edema were also investigated. The longitudinal relaxation time (T1) and apparent diffusion coefficient (D) were measured in the edematous area both in humans and in mice. D was calculated by using both mono- (Dmono) and biexponential (Dfast and Dslow) approaches in the low and overall range of b-values, respectively. The D values were correlated with the T1 values.ResultsA strong linear correlation was found between T1 and Dmono in vasogenic brain edema, both in humans and in mice. After breakdown of Dmono into fast and slow diffusing components, only Dfast exhibited a strong correlation with T1; Dslow was unchanged in vasogenic brain edema.A strong linear correlation was found between T1 and Dmono in vasogenic brain edema, both in humans and in mice. After breakdown of Dmono into fast and slow diffusing components, only Dfast exhibited a strong correlation with T1; Dslow was unchanged in vasogenic brain edema.ConclusionLarge b-value DWI can furnish a detailed characterization of vasogenic brain edema, and may provide a quantitative approach for the differentiation of edema types on the basis of the physicochemical properties of the water molecules. Application of the DWI method may permit prediction and follow-up of the effects of antiedematous therapy. J. Magn. Reson. Imaging 2007. © 2006 Wiley-Liss, Inc.Large b-value DWI can furnish a detailed characterization of vasogenic brain edema, and may provide a quantitative approach for the differentiation of edema types on the basis of the physicochemical properties of the water molecules. Application of the DWI method may permit prediction and follow-up of the effects of antiedematous therapy. J. Magn. Reson. Imaging 2007. © 2006 Wiley-Liss, Inc.

Research paper thumbnail of Application of mri for improved local control in complex radiotherapy of cervical cancer

Archive of Oncology, 2006

The aim of this study was to analyze the use of magnetic resonance imaging (MRI) as a modern medi... more The aim of this study was to analyze the use of magnetic resonance imaging (MRI) as a modern medical imaging technique in radiotherapy with special emphasis on the integration of MRI and a novel technique in brachytherapy to optimize treatment outcome in cervical cancer. Methods: In addition to the CT based shrinking volume conformal teletherapy in 31 patients with locally advanced cervical cancer, MRI examination with a special adjustable applicator at the treatment site was performed for the brachytherapy planning. To avoid excessive doses to the healthy structures during complex cervical radiotherapy isodose curves were calculated upon the information of the MR image and dose distribution was evaluated. Results: The consecutive application of CT and MRI limited the possibility for overdosage of the critical organs and undertreatment of the advanced tumor spread in all cases. The overall response rate for the complex treatment was 74.2% with complete regression in 25.8% of the cases. Based on the exact information of the three dimensional digital data radiation doses could be optimized without increasing the possibility of acute complications rate. Conclusion: The introduction of 3D treatment planning for teletherapy pelvic and boost irradiation of cervical carcinoma as well as for the brachytherapy part of the complex treatment is to be recommended.

Research paper thumbnail of Effects of intra- and extracellular space properties on diffusion and T 2 relaxation in a tissue model

Magnetic Resonance Imaging, 2009

The purpose of this study was to investigate the effects of biophysical factors on the diffusion ... more The purpose of this study was to investigate the effects of biophysical factors on the diffusion and the relaxation time T 2 independently. Certain properties of the extracellular and the intracellular space may change radically in pathological conditions resulting in water diffusion changes. A tissue model consisting of red blood cells was studied. The extra-and intracellular spaces were modified osmotically and by suspending medium concentration. Diffusion measurements were evaluated with regard to the effective medium theory. Neither the nature of the protein in the extracellular space nor an increased level of intracellular hydration caused a significant net water diffusion change in the cell suspension. The relaxation time T 2 exhibited very little dependence on the extracellular volume fraction or the concentration or the nature of the protein in the extracellular space. An increased level of intracellular hydration resulted in systematically larger T 2 values. It seems probable that increases in extracellular protein concentrations or in the extent of intracellular hydration do not play a significant role in the diffusion changes detected in pathological conditions. T 2 appears to depend on the level of hydration or the total water content but is seemingly less dependent of the concentration and the nature of the extracellular protein in our model solutions.

Research paper thumbnail of O-GlcNAc modification of proteins affects volume regulation in Jurkat cells

European Biophysics Journal With Biophysics Letters, 2010

An increasing amount of recent research has demonstrated that the hexosamine biosynthesis pathway... more An increasing amount of recent research has demonstrated that the hexosamine biosynthesis pathway (HBP) plays a significant role in the modulation of intracellular signaling transduction pathways, and affects cellular processes via modification of protein by O-linked β-N-acetylglucosamine (O-GlcNAc). Besides the many known and postulated effects of protein O-GlcNAc modifications, there is little available data on the role of O-GlcNAc in cellular volume regulation. Our objective was to test the effect of increased O-GlcNAc levels on hypotonia-induced volume changes in Jurkat cells. We pretreated Jurkat cells for 1 h with glucosamine (GlcN), PUGNAc (O-(2-acetamido-2-deoxy-d-glucopyranosylidene)-amino-N-phenylcarbamate) an inhibitor of O-GlcNAcase, or a high level of glucose to induce elevated levels of O-GlcNAc. We found that the response of Jurkat cells to hypotonic stress was significantly altered. The hypotonia induced cell-swelling was augmented in both GlcN and PUGNAc-treated cells and, to a lesser extent, in high glucose concentration-treated cells. Evaluated by NMR measurements, GlcN and PUGNAc treatment also significantly reduced intracellular water diffusion. Taken together, increased cell swelling and reduced water diffusion caused by elevated O-GlcNAc show notable analogy to the regulatory volume changes seen by magnetic resonance methods in nervous and other tissues in different pathological states. In conclusion, we demonstrate for the first time that protein O-GlcNAc could modulate cell volume regulation.

Research paper thumbnail of Does obstetric brachial plexus injury influence speech dominance

Annals of Neurology, 2009

ObjectiveRight-handedness and left-sided language lateralization is an unresolved mystery with un... more ObjectiveRight-handedness and left-sided language lateralization is an unresolved mystery with unknown cause/effect relations. Most studies suggest that the language lateralization is related to a fundamental brain asymmetry: right-handedness may be secondary. We analyzed the possibility of an opposite cause/effect relation: whether asymmetric hand usage (as a cause) can influence language lateralization (as a consequence).Right-handedness and left-sided language lateralization is an unresolved mystery with unknown cause/effect relations. Most studies suggest that the language lateralization is related to a fundamental brain asymmetry: right-handedness may be secondary. We analyzed the possibility of an opposite cause/effect relation: whether asymmetric hand usage (as a cause) can influence language lateralization (as a consequence).MethodsWe determined language lateralization by functional magnetic resonance imaging in 15 subjects whose upper limb (UL) had been injured at birth because of unilateral damage of the brachial plexus. These subjects were able to use only one (the noninjured) UL perfectly.We determined language lateralization by functional magnetic resonance imaging in 15 subjects whose upper limb (UL) had been injured at birth because of unilateral damage of the brachial plexus. These subjects were able to use only one (the noninjured) UL perfectly.ResultsWe found correlation between the severity of right-sided UL injuries and hand usage dysfunction and the degree of left-to-right shift of language lateralization. There was, however, not a complete switch of language lateralization.We found correlation between the severity of right-sided UL injuries and hand usage dysfunction and the degree of left-to-right shift of language lateralization. There was, however, not a complete switch of language lateralization.InterpretationRight-sided UL injury can induce a left-to-right shift in language lateralization, suggesting that hand usage can influence language lateralization. These findings may contradict the broadly accepted theory that right-handedness is a secondary phenomenon caused by left-sided hemispheric language lateralization. However, the cause/effect problem between asymmetric hand usage and language lateralization is not resolved in this study. Our findings may support the theory that gestures had a crucial role in human language evolution and is a part of the language system even today. Ann Neurol 2009;65:57–66Right-sided UL injury can induce a left-to-right shift in language lateralization, suggesting that hand usage can influence language lateralization. These findings may contradict the broadly accepted theory that right-handedness is a secondary phenomenon caused by left-sided hemispheric language lateralization. However, the cause/effect problem between asymmetric hand usage and language lateralization is not resolved in this study. Our findings may support the theory that gestures had a crucial role in human language evolution and is a part of the language system even today. Ann Neurol 2009;65:57–66

Research paper thumbnail of Implanted deep brain stimulator and 1.0Tesla magnetic resonance imaging

Journal of Magnetic Resonance Imaging, 2006

There is a great need for MRI examinations of patients who have previously undergone deep brain s... more There is a great need for MRI examinations of patients who have previously undergone deep brain stimulator (DBS) implantation. The current guidelines pertain only to a 1.5-Tesla horizontal-bore scanner complying with strict safety regulations. Moreover, almost all published in vitro and in vivo studies concerning patient safety are carried out on 1.5 Tesla MR scanners. The aim of our work is to share our clinical experience of 1.0-Tesla brain MR imaging. During the past four years, 34 patients with different types of implanted DBS systems underwent 1.0-Tesla MR examinations to answer diagnostic or clinical questions. Apart from the scanner type applied, all other safety instructions were strictly followed. The MRI itself made no significant difference to the measured impedances or the stimulation parameters required to achieve the optimal therapeutic results. From theoretical considerations, it may be assumed that 1.0-Tesla MRI can be performed safely on DBS-implanted patients, provided that all other recommendations are adhered to. J. Magn. Reson. Imaging 2006. © 2006 Wiley-Liss, Inc.

Research paper thumbnail of Osmotic and diffusive properties of intracellular water in camel erythrocytes: Effect of hemoglobin crowdedness

Cell Biology International, 2005

Camel erythrocytes have exceptional osmotic resistance and is believed to be due to augmented wat... more Camel erythrocytes have exceptional osmotic resistance and is believed to be due to augmented water-binding associated with the high hydrophilicity of camel hemoglobin. In practical terms this means that the proportion of osmotically non-removable water in camel erythrocytes is nearly 3-fold greater than that in human erythrocytes (w65 vs w20%). The relationship between water diffusion and the osmotic characteristics of intracellular water is the subject of this report.

Research paper thumbnail of Quantitative brain proton MR spectroscopy based on measurement of the relaxation time T 1 of water

Journal of Magnetic Resonance Imaging, 2008

PurposeTo provide a straightforward method for metabolite quantitation in the brain. Tissue water... more PurposeTo provide a straightforward method for metabolite quantitation in the brain. Tissue water concentration can be determined in a voxel by measuring T1 and it may provide an internal reference for the calculation of the metabolite concentrations.To provide a straightforward method for metabolite quantitation in the brain. Tissue water concentration can be determined in a voxel by measuring T1 and it may provide an internal reference for the calculation of the metabolite concentrations.Materials and MethodsWater-suppressed stimulated echo acquisition mode spectra were obtained at 1.5T, and the tissue water content was calculated from T1.Water-suppressed stimulated echo acquisition mode spectra were obtained at 1.5T, and the tissue water content was calculated from T1.ResultsThe calculated water content values demonstrated very good agreement with literature data. Metabolite concentrations (mmol/liter) in the gray and white matter: N-acetyl-aspartate = 14.02 ± 1.93, creatine = 9.98 ± 1.03, and choline = 1.14 ± 0.24; N-acetyl-aspartate = 11.08 ± 2.24, creatine = 7.83 ± 0.66, and choline = 2.05 ± 0.38, respectively.The calculated water content values demonstrated very good agreement with literature data. Metabolite concentrations (mmol/liter) in the gray and white matter: N-acetyl-aspartate = 14.02 ± 1.93, creatine = 9.98 ± 1.03, and choline = 1.14 ± 0.24; N-acetyl-aspartate = 11.08 ± 2.24, creatine = 7.83 ± 0.66, and choline = 2.05 ± 0.38, respectively.ConclusionThe water content calculated from T1 can yield an internal reference in MR spectroscopy, and the accurate measurement of metabolite concentrations is feasible. The proposed method is simple and can readily be applied in any MR center without the need for complicated corrections or calibration procedures. J. Magn. Reson. Imaging 2008;28:34–38. © 2008 Wiley-Liss, Inc.The water content calculated from T1 can yield an internal reference in MR spectroscopy, and the accurate measurement of metabolite concentrations is feasible. The proposed method is simple and can readily be applied in any MR center without the need for complicated corrections or calibration procedures. J. Magn. Reson. Imaging 2008;28:34–38. © 2008 Wiley-Liss, Inc.

Research paper thumbnail of History of simple febrile seizures is associated with hippocampal abnormalities in adults

Epilepsia, 2008

Background: It is unclear whether the hippocampal abnormality in temporal lobe epilepsy (TLE) is ... more Background: It is unclear whether the hippocampal abnormality in temporal lobe epilepsy (TLE) is a consequence or the cause of afebrile or febrile seizures (FSs). We investigated whether hippocampal abnormalities are present in healthy adults>15 years after a simple FS.Methods: Eight healthy subjects (5 men) with a history of simple FS (FS+ group) and eight sex- and aged-matched control subjects (FS– group) were investigated by three MR methods: blinded visual inspection of the MRI pictures; automatic voxel-based volumetry; and T2 relaxation time measurements.Results: The mean total volume of the two hippocampi was 5.36 ± 1.33 cm3in the FS+ group and 6.63 ± 1.46 cm3in the FS– group (p = 0.069). The T2 values in the anterior part of the left hippocampus (p = 0.036) and in the middle part of the right hippocampus (p = 0.025) were elevated in the FS+ subjects. The mean volume of the right hippocampus was 3.05 ± 0.8 cm3in the FS+ men and 4.05 ± 0.48 cm3in the FS– men (p = 0.043). The mean total volume of the two hippocampi was 5.38 ± 1.4 cm3in the FS+ men and 7.48 ± 1.14 cm3in the FS– men (p = 0.043). There were three FS+ men in whom hippocampal abnormalities including hippocampal sclerosis (HS) and dysgenesis were observed on visual inspection.Conclusions: A history of simple FS in childhood can be associated with hippocampal abnormalities in adults. These abnormalities are probably more pronounced in men. Simple FS may not be as a benign event as previously thought. Our findings suggest that hippocampal abnormalities associated with FS are not necessarily epileptogenic.

Research paper thumbnail of Atrophy and decreased activation of fronto-parietal attention areas contribute to higher visual dysfunction in posterior cortical atrophy

Psychiatry Research-neuroimaging, 2008

Voxel-based morphometry and functional magnetic resonance imaging demonstrated severe atrophy and... more Voxel-based morphometry and functional magnetic resonance imaging demonstrated severe atrophy and decreased activation of visual attention areas and occipital lobes in a patient with early posterior cortical atrophy compared with healthy controls and patients with early Alzheimer&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease. Our complex approach indicates that structures responsible for attention can be damaged early in posterior cortical atrophy and may contribute to the characteristic decline in higher visual functions.

Research paper thumbnail of Image registration improves human knee cartilage T1 mapping with delayed gadolinium-enhanced MRI of cartilage (dGEMRIC)

European Radiology, 2012

Objectives To evaluate the effect of automated registration in delayed gadolinium-enhanced MRI of... more Objectives To evaluate the effect of automated registration in delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) of the knee on the occurrence of movement artefacts on the T1 map and the reproducibility of region-of-interest (ROI)-based measurements. Methods Eleven patients with early-stage knee osteoarthritis and ten healthy controls underwent dGEMRIC twice at 3T. Controls underwent unenhanced imaging. ROIs were manually drawn on the femoral and tibial cartilage. T1 calculation was performed with and without registration of the T1weighted images. Automated three-dimensional rigid registration was performed on the femur and tibia cartilage separately. Registration quality was evaluated using the square root Cramér-Rao lower bound (CRLB σ). Additionally, the reproducibility of dGEMRIC was assessed by comparing automated registration with manual slice-matching. Results Automated registration of the T1-weighted images improved the T1 maps as the 90% percentile of the CRLB σ was significantly (P<0.05) reduced with a median reduction of 55.8 ms (patients) and 112.9 ms (controls). Manual matching and automated registration of the re-imaged T1 map gave comparable intraclass correlation coefficients of respectively 0.89/0.90 (patients) and 0.85/0.85 (controls). Conclusions Registration in dGEMRIC reduces movement artefacts on T1 maps and provides a good alternative to manual slice-matching in longitudinal studies. Key Points • Quantitative MRI is increasingly used for biomedical assessment of knee articular cartilage • Image registration leads to more accurate quantification of cartilage quality and damage • Movement artefacts in delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) are reduced • Automated image registration successfully aligns baseline and follow-up dGEMRIC examinations • Reproducibility of dGEMRIC with registration is similar to that using manual slice-matching

Research paper thumbnail of From signal-based to comprehensive magnetic resonance imaging

Scientific Reports

We present and evaluate a new insight into magnetic resonance imaging (MRI). It is based on the a... more We present and evaluate a new insight into magnetic resonance imaging (MRI). It is based on the algebraic description of the magnetization during the transient response—including intrinsic magnetic resonance parameters such as longitudinal and transverse relaxation times (T1, T2) and proton density (PD) and experimental conditions such as radiofrequency field (B1) and constant/homogeneous magnetic field (B0) from associated scanners. We exploit the correspondence among three different elements: the signal evolution as a result of a repetitive sequence of blocks of radiofrequency excitation pulses and encoding gradients, the continuous Bloch equations and the mathematical description of a sequence as a linear system. This approach simultaneously provides, in a single measurement, all quantitative parameters of interest as well as associated system imperfections. Finally, we demonstrate the in-vivo applicability of the new concept on a clinical MRI scanner.

Research paper thumbnail of Atrophy and decreased activation of fronto-parietal attention areas contribute to higher visual dysfunction in posterior cortical atrophy

Psychiatry Research: Neuroimaging, 2008

Voxel-based morphometry and functional magnetic resonance imaging demonstrated severe atrophy and... more Voxel-based morphometry and functional magnetic resonance imaging demonstrated severe atrophy and decreased activation of visual attention areas and occipital lobes in a patient with early posterior cortical atrophy compared with healthy controls and patients with early Alzheimer&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease. Our complex approach indicates that structures responsible for attention can be damaged early in posterior cortical atrophy and may contribute to the characteristic decline in higher visual functions.

Research paper thumbnail of 163 CELL TRACKING FOR CARTILAGE REPAIR USING SUPERPARAMAGNETIC IRON OXIDES: CLINICAL POTENTIAL

Osteoarthritis and Cartilage, 2010

maintain the mature chondrocyte phenotype avoiding terminal differentiation towards hypertrophy r... more maintain the mature chondrocyte phenotype avoiding terminal differentiation towards hypertrophy represents a major issue and is the objective of this study. Methods: Bone marrow-derived murine MSCs were induced to differentiate towards chondrocytes using the micropellet culture technique in presence of Wnt-6 containing conditioned medium (CM). CM was obtained after incubation of a chondrogenic medium consisting of DMEM supplemented with ITS, proline, ascorbic acid and sodium pyruvate for 48h on confluent NIH-3T3 cells stably transfected to secrete Wnt-6. As controls, CM from NIH-3T3 cells or BMP-2 containing medium was used. Similar conditions were used to obtain CM with osteogenic or adipogenic media. After 21 days, quantitative RT-PCR was performed on total RNA to detect the expression of markers specific for each lineage and staining specific for proteoglycans, mineralization or lipid droplets was performed. Western blotting with antiβ-catenin, anti-JNK or anti-PKC antibodies was performed after migration and transfer on nitrocellulose membranes of 20 μg total proteins extracted from pellets after a time course exposure to the different CM. Results: Pellet culture of murine MSCs in presence of NIH-derived CM or chondrogenic medium alone did not up-regulate the chondrocytic markers. On the contrary, Wnt-6 containing CM was sufficient to induce the differentiation of MSCs into chondrocytes as shown by the induction of collagen type IIB, aggrecan and COMP and a positive staining for proteoglycans. The expression levels of the transcripts were lower than those induced by BMP-2. However, contrary to BMP-2, we observed the lack of induction of the hypertrophic markers collagen type X and alkaline phosphatase when MSCs were cultured in Wnt-6 CM. Interestingly, in osteogenic or adipogenic conditions, MSCs did not up-regulate the markers specific for osteoblasts or adipocytes and rather decreased their expression level. The up-regulation of chondrocytic markers by Wnt-6 was associated with a lack of induction of the β-catenin or JNK pathways and preliminary results suggest that PKC signalling may be induced. Conclusions: Our results suggest that Wnt-6 is one new chondrogenic factor sufficient to specifically induce the generation of chondrocytes and inhibiting their terminal differentiation. Preliminary results suggest that Wnt-6 might induce the PKC-dependent pathway to activate the chondrocyte-specific genes.

Research paper thumbnail of Clinically Translatable Cell Tracking and Quantification by MRI in Cartilage Repair Using Superparamagnetic Iron Oxides

PLOS One, 2011

Background: Articular cartilage has very limited intrinsic regenerative capacity, making cell-bas... more Background: Articular cartilage has very limited intrinsic regenerative capacity, making cell-based therapy a tempting approach for cartilage repair. Cell tracking can be a major step towards unraveling and improving the repair process of these therapies. We studied superparamagnetic iron oxides (SPIO) for labeling human bone marrow-derived mesenchymal stem cells (hBMSCs) regarding effectivity, cell viability, long term metabolic cell activity, chondrogenic differentiation and hBMSC secretion profile. We additionally examined the capacity of synovial cells to endocytose SPIO from dead, labeled cells, together with the use of magnetic resonance imaging (MRI) for intra-articular visualization and quantification of SPIO labeled cells.

Research paper thumbnail of Der Einfluss der Fütterung auf die Zusammensetzung verschiedener Fettdepots von Jungbullen der Rassen Ungarisches Grauvieh und Holstein Friesian 2. Mitteilung: 1 H- Nuclear Magnetic Resonance (NMR) Untersuchungen

In this attempt the relaxation times using 1 H-NMR spectroscopy from three different (subcutaneou... more In this attempt the relaxation times using 1 H-NMR spectroscopy from three different (subcutaneous, perinephric and internal fat) fat depots of Hungarian Grey and Holstein Friesian extensive or intensive fattened young bulls were measured. The relaxation properties were compared with the analysis of fatty acid compostion. The different diets and the sample location have a higher influence on the relaxation times than the breed. In fat samples from extensive groups the T 1 -relaxation time was longer, while the T 2 -relaxation time was significantly shorter in intensive fed groups. The T 2 -relaxation time, as well as the relaxation time of T 21 -und T 22 -components were the shortest in extensive fed animals, while the proportion of T 21 -component was the highest in kidney fat, furthermore the difference was statistics proved. The T 2 -relaxation time showed a close negative relationship with the ratio of saturated fatty acids (SFA). The ratio of v 21 and v 22 depends on chemical composition of fat samples. In fat tissues with a high SFA percentage caused a higher proportion of v 21 . It is suggested that differences in fatty acid compositon of fat samples caused also alteration in the relaxation time.

Research paper thumbnail of In vivo brain edema classification: New insight offered by large b-value diffusion-weighted MR imaging

Journal of Magnetic Resonance Imaging, 2007

PurposeTo assess the role of large b-value diffusion weighted imaging (DWI) in the characterizati... more PurposeTo assess the role of large b-value diffusion weighted imaging (DWI) in the characterization of the physicochemical properties of the water in brain edema under experimental and clinical conditions.To assess the role of large b-value diffusion weighted imaging (DWI) in the characterization of the physicochemical properties of the water in brain edema under experimental and clinical conditions.Materials and MethodsVasogenic brain edema was induced in mice by means of cold injury. A total of 17 patients with extensive peritumoral brain edema were also investigated. The longitudinal relaxation time (T1) and apparent diffusion coefficient (D) were measured in the edematous area both in humans and in mice. D was calculated by using both mono- (Dmono) and biexponential (Dfast and Dslow) approaches in the low and overall range of b-values, respectively. The D values were correlated with the T1 values.Vasogenic brain edema was induced in mice by means of cold injury. A total of 17 patients with extensive peritumoral brain edema were also investigated. The longitudinal relaxation time (T1) and apparent diffusion coefficient (D) were measured in the edematous area both in humans and in mice. D was calculated by using both mono- (Dmono) and biexponential (Dfast and Dslow) approaches in the low and overall range of b-values, respectively. The D values were correlated with the T1 values.ResultsA strong linear correlation was found between T1 and Dmono in vasogenic brain edema, both in humans and in mice. After breakdown of Dmono into fast and slow diffusing components, only Dfast exhibited a strong correlation with T1; Dslow was unchanged in vasogenic brain edema.A strong linear correlation was found between T1 and Dmono in vasogenic brain edema, both in humans and in mice. After breakdown of Dmono into fast and slow diffusing components, only Dfast exhibited a strong correlation with T1; Dslow was unchanged in vasogenic brain edema.ConclusionLarge b-value DWI can furnish a detailed characterization of vasogenic brain edema, and may provide a quantitative approach for the differentiation of edema types on the basis of the physicochemical properties of the water molecules. Application of the DWI method may permit prediction and follow-up of the effects of antiedematous therapy. J. Magn. Reson. Imaging 2007. © 2006 Wiley-Liss, Inc.Large b-value DWI can furnish a detailed characterization of vasogenic brain edema, and may provide a quantitative approach for the differentiation of edema types on the basis of the physicochemical properties of the water molecules. Application of the DWI method may permit prediction and follow-up of the effects of antiedematous therapy. J. Magn. Reson. Imaging 2007. © 2006 Wiley-Liss, Inc.

Research paper thumbnail of Application of mri for improved local control in complex radiotherapy of cervical cancer

Archive of Oncology, 2006

The aim of this study was to analyze the use of magnetic resonance imaging (MRI) as a modern medi... more The aim of this study was to analyze the use of magnetic resonance imaging (MRI) as a modern medical imaging technique in radiotherapy with special emphasis on the integration of MRI and a novel technique in brachytherapy to optimize treatment outcome in cervical cancer. Methods: In addition to the CT based shrinking volume conformal teletherapy in 31 patients with locally advanced cervical cancer, MRI examination with a special adjustable applicator at the treatment site was performed for the brachytherapy planning. To avoid excessive doses to the healthy structures during complex cervical radiotherapy isodose curves were calculated upon the information of the MR image and dose distribution was evaluated. Results: The consecutive application of CT and MRI limited the possibility for overdosage of the critical organs and undertreatment of the advanced tumor spread in all cases. The overall response rate for the complex treatment was 74.2% with complete regression in 25.8% of the cases. Based on the exact information of the three dimensional digital data radiation doses could be optimized without increasing the possibility of acute complications rate. Conclusion: The introduction of 3D treatment planning for teletherapy pelvic and boost irradiation of cervical carcinoma as well as for the brachytherapy part of the complex treatment is to be recommended.

Research paper thumbnail of Effects of intra- and extracellular space properties on diffusion and T 2 relaxation in a tissue model

Magnetic Resonance Imaging, 2009

The purpose of this study was to investigate the effects of biophysical factors on the diffusion ... more The purpose of this study was to investigate the effects of biophysical factors on the diffusion and the relaxation time T 2 independently. Certain properties of the extracellular and the intracellular space may change radically in pathological conditions resulting in water diffusion changes. A tissue model consisting of red blood cells was studied. The extra-and intracellular spaces were modified osmotically and by suspending medium concentration. Diffusion measurements were evaluated with regard to the effective medium theory. Neither the nature of the protein in the extracellular space nor an increased level of intracellular hydration caused a significant net water diffusion change in the cell suspension. The relaxation time T 2 exhibited very little dependence on the extracellular volume fraction or the concentration or the nature of the protein in the extracellular space. An increased level of intracellular hydration resulted in systematically larger T 2 values. It seems probable that increases in extracellular protein concentrations or in the extent of intracellular hydration do not play a significant role in the diffusion changes detected in pathological conditions. T 2 appears to depend on the level of hydration or the total water content but is seemingly less dependent of the concentration and the nature of the extracellular protein in our model solutions.

Research paper thumbnail of O-GlcNAc modification of proteins affects volume regulation in Jurkat cells

European Biophysics Journal With Biophysics Letters, 2010

An increasing amount of recent research has demonstrated that the hexosamine biosynthesis pathway... more An increasing amount of recent research has demonstrated that the hexosamine biosynthesis pathway (HBP) plays a significant role in the modulation of intracellular signaling transduction pathways, and affects cellular processes via modification of protein by O-linked β-N-acetylglucosamine (O-GlcNAc). Besides the many known and postulated effects of protein O-GlcNAc modifications, there is little available data on the role of O-GlcNAc in cellular volume regulation. Our objective was to test the effect of increased O-GlcNAc levels on hypotonia-induced volume changes in Jurkat cells. We pretreated Jurkat cells for 1 h with glucosamine (GlcN), PUGNAc (O-(2-acetamido-2-deoxy-d-glucopyranosylidene)-amino-N-phenylcarbamate) an inhibitor of O-GlcNAcase, or a high level of glucose to induce elevated levels of O-GlcNAc. We found that the response of Jurkat cells to hypotonic stress was significantly altered. The hypotonia induced cell-swelling was augmented in both GlcN and PUGNAc-treated cells and, to a lesser extent, in high glucose concentration-treated cells. Evaluated by NMR measurements, GlcN and PUGNAc treatment also significantly reduced intracellular water diffusion. Taken together, increased cell swelling and reduced water diffusion caused by elevated O-GlcNAc show notable analogy to the regulatory volume changes seen by magnetic resonance methods in nervous and other tissues in different pathological states. In conclusion, we demonstrate for the first time that protein O-GlcNAc could modulate cell volume regulation.

Research paper thumbnail of Does obstetric brachial plexus injury influence speech dominance

Annals of Neurology, 2009

ObjectiveRight-handedness and left-sided language lateralization is an unresolved mystery with un... more ObjectiveRight-handedness and left-sided language lateralization is an unresolved mystery with unknown cause/effect relations. Most studies suggest that the language lateralization is related to a fundamental brain asymmetry: right-handedness may be secondary. We analyzed the possibility of an opposite cause/effect relation: whether asymmetric hand usage (as a cause) can influence language lateralization (as a consequence).Right-handedness and left-sided language lateralization is an unresolved mystery with unknown cause/effect relations. Most studies suggest that the language lateralization is related to a fundamental brain asymmetry: right-handedness may be secondary. We analyzed the possibility of an opposite cause/effect relation: whether asymmetric hand usage (as a cause) can influence language lateralization (as a consequence).MethodsWe determined language lateralization by functional magnetic resonance imaging in 15 subjects whose upper limb (UL) had been injured at birth because of unilateral damage of the brachial plexus. These subjects were able to use only one (the noninjured) UL perfectly.We determined language lateralization by functional magnetic resonance imaging in 15 subjects whose upper limb (UL) had been injured at birth because of unilateral damage of the brachial plexus. These subjects were able to use only one (the noninjured) UL perfectly.ResultsWe found correlation between the severity of right-sided UL injuries and hand usage dysfunction and the degree of left-to-right shift of language lateralization. There was, however, not a complete switch of language lateralization.We found correlation between the severity of right-sided UL injuries and hand usage dysfunction and the degree of left-to-right shift of language lateralization. There was, however, not a complete switch of language lateralization.InterpretationRight-sided UL injury can induce a left-to-right shift in language lateralization, suggesting that hand usage can influence language lateralization. These findings may contradict the broadly accepted theory that right-handedness is a secondary phenomenon caused by left-sided hemispheric language lateralization. However, the cause/effect problem between asymmetric hand usage and language lateralization is not resolved in this study. Our findings may support the theory that gestures had a crucial role in human language evolution and is a part of the language system even today. Ann Neurol 2009;65:57–66Right-sided UL injury can induce a left-to-right shift in language lateralization, suggesting that hand usage can influence language lateralization. These findings may contradict the broadly accepted theory that right-handedness is a secondary phenomenon caused by left-sided hemispheric language lateralization. However, the cause/effect problem between asymmetric hand usage and language lateralization is not resolved in this study. Our findings may support the theory that gestures had a crucial role in human language evolution and is a part of the language system even today. Ann Neurol 2009;65:57–66

Research paper thumbnail of Implanted deep brain stimulator and 1.0Tesla magnetic resonance imaging

Journal of Magnetic Resonance Imaging, 2006

There is a great need for MRI examinations of patients who have previously undergone deep brain s... more There is a great need for MRI examinations of patients who have previously undergone deep brain stimulator (DBS) implantation. The current guidelines pertain only to a 1.5-Tesla horizontal-bore scanner complying with strict safety regulations. Moreover, almost all published in vitro and in vivo studies concerning patient safety are carried out on 1.5 Tesla MR scanners. The aim of our work is to share our clinical experience of 1.0-Tesla brain MR imaging. During the past four years, 34 patients with different types of implanted DBS systems underwent 1.0-Tesla MR examinations to answer diagnostic or clinical questions. Apart from the scanner type applied, all other safety instructions were strictly followed. The MRI itself made no significant difference to the measured impedances or the stimulation parameters required to achieve the optimal therapeutic results. From theoretical considerations, it may be assumed that 1.0-Tesla MRI can be performed safely on DBS-implanted patients, provided that all other recommendations are adhered to. J. Magn. Reson. Imaging 2006. © 2006 Wiley-Liss, Inc.

Research paper thumbnail of Osmotic and diffusive properties of intracellular water in camel erythrocytes: Effect of hemoglobin crowdedness

Cell Biology International, 2005

Camel erythrocytes have exceptional osmotic resistance and is believed to be due to augmented wat... more Camel erythrocytes have exceptional osmotic resistance and is believed to be due to augmented water-binding associated with the high hydrophilicity of camel hemoglobin. In practical terms this means that the proportion of osmotically non-removable water in camel erythrocytes is nearly 3-fold greater than that in human erythrocytes (w65 vs w20%). The relationship between water diffusion and the osmotic characteristics of intracellular water is the subject of this report.

Research paper thumbnail of Quantitative brain proton MR spectroscopy based on measurement of the relaxation time T 1 of water

Journal of Magnetic Resonance Imaging, 2008

PurposeTo provide a straightforward method for metabolite quantitation in the brain. Tissue water... more PurposeTo provide a straightforward method for metabolite quantitation in the brain. Tissue water concentration can be determined in a voxel by measuring T1 and it may provide an internal reference for the calculation of the metabolite concentrations.To provide a straightforward method for metabolite quantitation in the brain. Tissue water concentration can be determined in a voxel by measuring T1 and it may provide an internal reference for the calculation of the metabolite concentrations.Materials and MethodsWater-suppressed stimulated echo acquisition mode spectra were obtained at 1.5T, and the tissue water content was calculated from T1.Water-suppressed stimulated echo acquisition mode spectra were obtained at 1.5T, and the tissue water content was calculated from T1.ResultsThe calculated water content values demonstrated very good agreement with literature data. Metabolite concentrations (mmol/liter) in the gray and white matter: N-acetyl-aspartate = 14.02 ± 1.93, creatine = 9.98 ± 1.03, and choline = 1.14 ± 0.24; N-acetyl-aspartate = 11.08 ± 2.24, creatine = 7.83 ± 0.66, and choline = 2.05 ± 0.38, respectively.The calculated water content values demonstrated very good agreement with literature data. Metabolite concentrations (mmol/liter) in the gray and white matter: N-acetyl-aspartate = 14.02 ± 1.93, creatine = 9.98 ± 1.03, and choline = 1.14 ± 0.24; N-acetyl-aspartate = 11.08 ± 2.24, creatine = 7.83 ± 0.66, and choline = 2.05 ± 0.38, respectively.ConclusionThe water content calculated from T1 can yield an internal reference in MR spectroscopy, and the accurate measurement of metabolite concentrations is feasible. The proposed method is simple and can readily be applied in any MR center without the need for complicated corrections or calibration procedures. J. Magn. Reson. Imaging 2008;28:34–38. © 2008 Wiley-Liss, Inc.The water content calculated from T1 can yield an internal reference in MR spectroscopy, and the accurate measurement of metabolite concentrations is feasible. The proposed method is simple and can readily be applied in any MR center without the need for complicated corrections or calibration procedures. J. Magn. Reson. Imaging 2008;28:34–38. © 2008 Wiley-Liss, Inc.

Research paper thumbnail of History of simple febrile seizures is associated with hippocampal abnormalities in adults

Epilepsia, 2008

Background: It is unclear whether the hippocampal abnormality in temporal lobe epilepsy (TLE) is ... more Background: It is unclear whether the hippocampal abnormality in temporal lobe epilepsy (TLE) is a consequence or the cause of afebrile or febrile seizures (FSs). We investigated whether hippocampal abnormalities are present in healthy adults>15 years after a simple FS.Methods: Eight healthy subjects (5 men) with a history of simple FS (FS+ group) and eight sex- and aged-matched control subjects (FS– group) were investigated by three MR methods: blinded visual inspection of the MRI pictures; automatic voxel-based volumetry; and T2 relaxation time measurements.Results: The mean total volume of the two hippocampi was 5.36 ± 1.33 cm3in the FS+ group and 6.63 ± 1.46 cm3in the FS– group (p = 0.069). The T2 values in the anterior part of the left hippocampus (p = 0.036) and in the middle part of the right hippocampus (p = 0.025) were elevated in the FS+ subjects. The mean volume of the right hippocampus was 3.05 ± 0.8 cm3in the FS+ men and 4.05 ± 0.48 cm3in the FS– men (p = 0.043). The mean total volume of the two hippocampi was 5.38 ± 1.4 cm3in the FS+ men and 7.48 ± 1.14 cm3in the FS– men (p = 0.043). There were three FS+ men in whom hippocampal abnormalities including hippocampal sclerosis (HS) and dysgenesis were observed on visual inspection.Conclusions: A history of simple FS in childhood can be associated with hippocampal abnormalities in adults. These abnormalities are probably more pronounced in men. Simple FS may not be as a benign event as previously thought. Our findings suggest that hippocampal abnormalities associated with FS are not necessarily epileptogenic.

Research paper thumbnail of Atrophy and decreased activation of fronto-parietal attention areas contribute to higher visual dysfunction in posterior cortical atrophy

Psychiatry Research-neuroimaging, 2008

Voxel-based morphometry and functional magnetic resonance imaging demonstrated severe atrophy and... more Voxel-based morphometry and functional magnetic resonance imaging demonstrated severe atrophy and decreased activation of visual attention areas and occipital lobes in a patient with early posterior cortical atrophy compared with healthy controls and patients with early Alzheimer&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease. Our complex approach indicates that structures responsible for attention can be damaged early in posterior cortical atrophy and may contribute to the characteristic decline in higher visual functions.