Effect of methylprednisolone on experimental brain edema in magnetic resonance imaging.

Magnetic resonance imaging has been used for evaluating of a brain edema in experimental animals to assess cytotoxic and vasogenic edema by the apparent diffusion coefficient (ADC) and T2 imaging. This paper brings information about the effectiveness of methylprednisolone (MP) on experimental brain edema. A total of 24 rats were divided into three groups of 8 animals each. Rats with cytotoxic/intracellular brain edema induced by water intoxication were assigned to the group WI. These rats also served as the additional control group CG when measured before the induction of edema. A third group (WIMP) was intraperitoneally administered with methylprednisolone 100 mg/kg during water intoxication treatment. The group WI+MP was injected with methylprednisolone 50 mg/kg into the carotid artery within two hours after the water intoxication treatment. We evaluated the results in four groups. Two control groups (CG, WI) and two experimental groups (WIMP, WI+MP). Rats were subjected to MR scanning 24 h after edema induction. We observed significantly increased ADC values in group WI in both evaluated areas - cortex and hippocampus, which proved the occurrence of experimental vasogenic edema, while ADC values in groups WIMP and WI+MP were not increased, indicating that the experimental edema was not developed and thus confirming the protective effect of MP.

A Trimodal Imaging Platform for Tracking Viable Transplanted Pancreatic Islets In Vivo: F-19 MR, Fluorescence, and Bioluminescence Imaging.

PURPOSE: Combining specific and quantitative F-19 magnetic resonance imaging (MRI) with sensitive and convenient optical imaging provides complementary information about the distribution and viability of transplanted pancreatic islet grafts. In this study, pancreatic islets (PIs) were labeled with positively charged multimodal nanoparticles based on poly(lactic-co-glycolic acid) (PLGA-NPs) with encapsulated perfluoro-15-crown-5-ether and the near-infrared fluorescent dye indocyanine green. PROCEDURES: One thousand and three thousand bioluminescent PIs were transplanted into subcutaneous artificial scaffolds, which served as an alternative transplant site. The grafts were monitored using in vivo F-19 MR, fluorescence, and bioluminescence imaging in healthy rats for 2 weeks. RESULTS: Transplanted PIs were unambiguously localized in the scaffolds by F-19 MRI throughout the whole experiment. Fluorescence was detected in the first 4 days after transplantation only. Importantly, in vivo bioluminescence correlated with the F-19 MRI signal. CONCLUSIONS: We developed a trimodal imaging platform for in vivo examination of transplanted PIs. Fluorescence imaging revealed instability of the fluorescent dye and its limited applicability for longitudinal in vivo studies. A correlation between the bioluminescence signal and the F-19 MRI signal indicated the fast clearance of PLGA-NPs from the transplantation site after cell death, which addresses a major issue with intracellular imaging labels. Therefore, the proposed PLGA-NP platform is reliable for reflecting the status of transplanted PIs in vivo.

Differences in muscle metabolism in patients with type I diabetes - influence of gender and nephropathy studied by (31)P MR spectroscopy.

Type I diabetes mellitus (DM1) is a complex disease with adverse effects on organs and tissues despite compensation by insulin treatment. The goal of our study was to study how kidney diseases change (31)P MR parameters of muscle metabolism in DM1 patients with respect to gender. 51 DM1 patients (19 m/14 f without and 13 m/5 f with nephropathy) and 26 (14 m/12 f) healthy volunteers were examined using (31)P magnetic resonance spectroscopy at 3T tomograph at rest, and during and after a calf muscle exercise. The exercise consisted of a six-minute plantar flexion using a pedal ergometer followed by a six-minute recovery. It is reflected by reduced relative beta-ATP and increased Pi and phosphodiester signals to phosphocreatine (PCr) at rest and prolongation of the PCr recovery time after the exercise. Measurement on healthy volunteers indicated differences between males and females in pH at the rest and after the exercise only. These differences between patients groups were not significant. We have proven that nephropathy affects the metabolism in diabetic patients and our results confirm significant difference between patients with and without nephropathy. Gender differences in pH were observed only between male and female healthy volunteers.

Minipig model of Huntington's disease: ¹H magnetic resonance spectroscopy of the brain.

Huntington's disease (HD) is an inherited autosomal neurodegenerative disorder affecting predominantly the brain, characterized by motor dysfunctions, behavioral and cognitive disturbances. The aim of this study was to determine changes in the brain of transgenic minipigs before HD onset using (1)H magnetic resonance (MR) spectroscopy. Measurements were performed on a 3 T MR scanner using a single voxel spectroscopy sequence for spectra acquisition in the white matter and chemical shift imaging sequence for measurement in the striatum, hippocampus and thalamus. A decrease of (phospho)creatine (tCr) concentration was found only in the thalamus (p=0.002) of transgenic minipigs, nevertheless we found significant changes in metabolite ratios. Increase of the ratio choline compounds (tCho)/tCr was found in all examined areas: striatum (p=0.010), thalamus (p=0.011) as well as hippocampus (p=0.027). The ratio N-acetylaspartate+N-acetylaspartylglutamate (tNAA)/tCr (p=0.043) and glutamate+glutamine (Glx)/tCr (p=0.039) was elevated in the thalamus, the ratio myo-inositol (Ins)/tCr (p=0.048) was significantly increased in the hippocampus. No significant differences were observed in the metabolite concentrations in the white matter, however we found significant increase of ratios tNAA/tCr (p=0.018) and tCho/tCr (p=0.003) ratios in transgenic boars. We suppose that the majority of the observed changes are predominantly related to changes in energy metabolism caused by decrease of tCr.

The relationships between quantitative MR parameters in hippocampus in healthy subjects and patients with temporal lobe epilepsy.

We introduce a new magnetic resonance (MR) method based on a pixel-by-pixel image processing to examine relationships between metabolic and structural processes in the pathologic hippocampus. The method was tested for lateralization of the epileptogenic zone in patients with temporal lobe epilepsy (TLE). Twenty patients with drug-resistant TLE and fifteen healthy controls were examined at 3T. The measurement protocol contained T2-weighted MR images, spectroscopic imaging, diffusion tensor imaging and T2 relaxometry. Correlations between quantitative MR parameters were calculated on a pixel-by-pixel basis using the CORIMA program which enables automated pixel identification in the normal tissue according to control data. All MR parameters changed in the anteroposterior direction in the hippocampus and correlation patterns and their slopes differed between patients and controls. Combinations of T2 relaxation times with metabolite values represent the best biomarkers of the epileptogenic zone. Correlations with mean diffusivity did not provide sufficiently accurate results due to diffusion image distortions. Quantitative MR analysis non-invasively provides a detailed description of hippocampal pathology and may represent complementary tool to the standard clinical protocol. However, the automated processing should be carefully monitored in order to avoid possible errors caused by MR artifacts.

Detection of pancreatic islet allograft impairment in advance of functional failure using magnetic resonance imaging.

This study evaluated the ability of magnetic resonance imaging (MRI) to predict failure of pancreatic islets (PI) transplanted into the hepatic portal vein. Brown-Norway (n = 18) and Lewis (n = 6) rats received islets isolated from Lewis donors. The rejection process in Brown-Norway recipients was mitigated by two different immunosuppressive regimens [tacrolimus + hydrocortisone for 3 months (n = 6) or tacrolimus for 12 days (n = 12)]. Longitudinal MRI monitoring of recipients at post-transplantation weeks 1, 2, 3, 4, 6, 8, 10, and 12 confirmed the ability to detect SPIO labeled PI after transplantation into the liver. The relative number of MRI signals related to PI isografts remained stable up to study completion. Recipients of PI allografts were normoglycemic until the end of study; signals declined gradually to 44 ± 17% in these animals. In animals with islets failure during post-transplant week 12, the number of signals decreased to 25 ± 10% of initial values. The difference between groups (islet function/failed) became significant post-transplant week 3. Our data demonstrate that the MRI changes attributable to rejection become apparent within 3 weeks after transplantation, i.e. at least 8 weeks before functional allograft failure.

In vivo 31P MR spectroscopy of human kidney grafts using the 2D-chemical shift imaging method.

The aim of this work was to evaluate the possibility to use in vivo (31)P magnetic resonance spectroscopy (MRS) for the diagnosis of kidney graft dysfunction after transplantation. We examined 68 kidney grafted patients using a 1.5 T MR scanner. (31)P MRS was performed using the 2D-chemical shift imaging method. The patients were divided into 4 groups: acute rejection episode; acute tubular necrosis; late graft dysfunction; or good renal function. We measured the signal intensities of phosphomonoesters (PME), inorganic phosphate (Pi), phosphodiesters (PDE), and α-, ß-, γ-adenosine triphosphate (ATP; with contributions of α- and ß-adenosine diphosphate) and their ratios. Patients with an acute rejection episodes showed a significantly elevated PME/ß-ATP and PDE/ß-ATP, PME/Pi, and PDE/Pi signal ratios compared with the control group. The group with acute tubular necrosis had decreased ratios. Patients with late graft dysfunction revealed only an insignificant decrease in PME/Pi and PDE/Pi ratios. We concluded that (31)P MRS was capable of distinguishing the two main causes of graft dysfunction early after transplantation.

Core-shell La(1-x)Sr(x)MnO3 nanoparticles as colloidal mediators for magnetic fluid hyperthermia.

Core-shell nanoparticles consisting of La(0.75)Sr(0.25)MnO(3) cores covered by silica were synthesized by a procedure consisting of several steps, including the sol-gel method in the presence of citric acid and ethylene glycol, thermal and mechanical treatment, encapsulation employing tetraethoxysilane and final separation by centrifugation in order to get the required size fraction. Morphological studies revealed well-separated particles that form a stable water suspension. Magnetic studies include magnetization measurements and investigation of the ferromagnetic-superparamagnetic-paramagnetic transition. Magnetic heating experiments in 'calorimetric mode' were used to determine the heating efficiency of the particles in water suspension and further employed for biological studies of extracellular and intracellular effects analysed by tests of viability.

Lesion evolution after gamma knife irradiation observed by magnetic resonance imaging.

PURPOSE: Our study is focused on the magnetic resonance imaging (MRI) observation of lesion development and hippocampus related functional impairments in rats after irradiation with a Leksell Gamma knife (LGK). MATERIALS AND METHODS: We exposed 32 three-month-old Long-Evans rats to various radiation doses (25 Gy, 50 Gy or 75 Gy). The rats were scanned by a 4.7 T magnetic resonance (MR) spectrometer at several timepoints (1 - 18 months) after irradiation. The lesion size was evaluated by manual segmentation; the animals were behaviorally tested in a Morris water maze and examined histologically. RESULTS: We found that a dose of 25 Gy induced no edema, necrosis or behavioral change. The response of the rats to higher doses was not uniform; the first occurrence of lesions in the rat brains irradiated with 50 and 75 Gy was detected six months post-irradiation. Functional impairment correlated well with the lesion size and histology. CONCLUSIONS: Rat brains showed the development of expanding delayed lesions after 50 or 75 Gy doses from the LGK during the first year after irradiation.

Chronic liver disease: relaxometry in the brain after liver transplantation.

Relaxometry revealed changes in the basal ganglia in T(1) and T(2) relaxation times due to liver disease. Manganese is probably responsible for T(1) and T(2) shortening (as the concentration is known to be higher in both the liver and blood due to hepatic cirrhosis). The aim of this study was to follow possible recovery after liver transplantation by MR relaxometry. Together with a group of 20 healthy volunteers we scanned 53 patients before and after liver transplantation (some of them repeatedly). Both T(1) and T(2) values were evaluated in the basal ganglia, thalamus, and frontal white matter. T(1) relaxation time was shortened by approx. 20-25% compared to the control group, probably the result of manganese deposition in the brain caused by hepatic cirrhosis. After liver transplantation the relaxation time recovered gradually with almost normal values reached approx. 2 years after surgery. T(1) recovery was observed in all evaluated structures. Similar results were observed with T(2) relaxation in the basal ganglia and thalamus. In the white matter T(2) remained low even 2 years after surgery.

Dynamic relaxometry: application to iron uptake by ferritin.

We introduce dynamic relaxometry as a novel technique for studying biochemical reactions, such as those leading to mineral formation (biomineralization). This technique was applied to follow the time course of iron oxidation and hydrolysis by the protein ferritin. Horse spleen apoferritin was loaded with single additions of 4, 10, 20, 40, and 100 ferrous ions per protein, and with multiple additions of 4, 10, 20, and 100 ferrous ions. The NMR T2 relaxation time was then measured sequentially and continuously for up to 24 h. At low loading factors of 4-10 Fe atoms/molecule, the iron is rapidly bound and oxidized by the protein on a time scale of approximately 15 s to several minutes. At intermediate loading factors (10-40), rapid initial oxidation was observed, followed by the formation of antiferromagnetic clusters. This process occurred at a much slower rate and continued for up to several hours, but was inhibited at lower pH values. At higher loading factors (40-1000), iron oxidation may occur directly on the core, and this process may continue for up to 24 h following the initial loading. Dynamic relaxometry appears to be a potentially powerful technique that may well have applications beyond the study of iron uptake by the ferritin protein.

Neurotransplantation of magnetically labeled oligodendrocyte progenitors: magnetic resonance tracking of cell migration and myelination.

Demyelination is a common pathological finding in human neurological diseases and frequently persists as a result of failure of endogenous repair. Transplanted oligodendrocytes and their precursor cells can (re)myelinate axons, raising the possibility of therapeutic intervention. The migratory capacity of transplanted cells is of key importance in determining the extent of (re)myelination and can, at present, be evaluated only by using invasive and irreversible procedures. We have exploited the transferrin receptor as an efficient intracellular delivery device for magnetic nanoparticles, and transplanted tagged oligodendrocyte progenitor cells into the spinal cord of myelin-deficient rats. Cell migration could be easily detected by using three-dimensional magnetic resonance microscopy, with a close correlation between the areas of contrast enhancement and the achieved extent of myelination. The present results demonstrate that magnetic resonance tracking of transplanted oligodendrocyte progenitors is feasible; this technique has the potential to be easily extended to other neurotransplantation studies involving different precursor cell types.

MR relaxometry on a whole-body imager: quality control.

Long-term monitoring of the average proton relaxation time T2 of phantoms measured on a Siemens MR whole-body imager showed very good repeatability and reproducibility. The repeatability (short-term precision) and reproducibility (long-term precision) of the average values of a relaxation time T2 approximately/= 81 ms, obtained by a standard 16-echo CPMG pulse sequence, were 2.6% and 9.7%, respectively. The Siemens Vision imager proved to be a suitable tool for T2 evaluation in vivo. Quality control was performed using the techniques of control diagrams developed by Shewhart, which proved to be an appropriate method for continuous quality control of relaxation time determination.

Synthesis and relaxometry of high-generation (G = 5, 7, 9, and 10) PAMAM dendrimer-DOTA-gadolinium chelates.

A series of high-generation (G) ethylenediamine-core polyamidoamine (PAMAM) dendrimers corresponding to G = 5, 7, 9, and 10 were conjugated with the bifunctional chelate 2-(4-isothiocyanatobenzyl)- 1,4,7,10-tetraazacyclododecane-N,N',N",N"'-tetraacetate (p-SCN-Bz-DOTA). Gadolinium (III) ion was added to the macromolecules, and the 1/T1 and 1/T2 NMRD profiles were measured at 3 degrees, 23 degrees, and 37 degrees C. The synthesis resulted in preparations that ranged from an average of 127 chelates and 96 Gd3+ ions per G = 5 dendrimer to an average of 3727 chelates and 1860 Gd3+ ions per G = 10 dendrimer. At 20 MHz and 23 degrees C, the 1/T1 ion relaxivity increased from 30 mM(-1) s(-1) for the G = 5 to 35 mM(-1) s(-1) for the G = 7 PAMAM dendrimer-DOTA-Gd, reaching a plateau at 36 mM(-1) s(-1) for the G = 9 and G = 10 dendrimers. A similar plateau was observed for 1/T2 with values of 36 mM(-1) s(-1) for G = 5, 42 mM(-1) s(-1) for G = 7, and 45 mM(-1) s(-1) for the G = 9 and G = 10 dendrimers. This "saturation" of ion relaxivity for high-generation dendrimers occurred over the entire frequency range studied. The 1/T1 and 1/T2 relaxivities decreased as the temperature decreased for each generation of dendrimer studied, implying that slow water exchange of bound water molecules with the bulk solvent limits the relaxivity. In such circumstances, increases in the rotational correlation time of the macromolecules associated with higher generations of dendrimer does not result in significant increases in the ion relaxivity. Although the ion relaxivity does not increase, the total molecular relaxivities increased from 2880 mM(-1) s(-1) to 66960 mM(-1) s(-1) for the G = 5 to the G = 10 dendrimer. The current findings are relevant for the design of high-generation dendrimer-based receptor agents.

T2 relaxation time study of the pig renal allografts.

A previous study showed the possibility of the dependence of the T2 maps measured by Siemens Magnetom MR imager 1.5 T on the viability of the cadaveric kidney. For the T2 relaxometry study the pig model was used. Ten pig renal allografts were examined during 68 h after removal. Significant differences were found in the change of the initial Tini2 values in the histogram within the first 20 h [delta 1 = Tini2 (2) - Tini2 (20)] or 8 h [delta 2 = Tini2 (2) - Tini2 (8)] after removal between the groups of the damaged kidneys (delta 1 = 20.2 +/- 6.8 ms, delta 2 = 19.4 +/- 3.0) and the kidneys without apparent damage (delta 1 = 9.4 +/- 8.5 ms, delta 2 = 5.4 +/- 5.8).

Potential of 31P magnetic resonance spectroscopy in monitoring the viability of human renal grafts stored in Euro-Collins perfusion solution.

The relative concentrations of inorganic phosphate and phosphomonoesters (PME) of 18 human cadaveric kidneys stored in Euro-Collins perfusion solution were measured by 31P MR spectroscopy. The signals of intracellular inorganic phosphate (Pii) and inorganic phosphate contained in the perfusion solution (Pie) were separated by the deconvolution technique. The ratio of the signal intensities of phosphomonoesters and intracellular inorganic phosphate (PME/Pii) was used as a marker of kidney viability and correlated with kidney function after transplantation. Separation of the Pii and Pie signals in the measured spectra was successful in 72% of kidneys. The results of MR analysis satisfactorily agree in 78% with the post-transplant function of kidneys.