Correlation of proton transverse relaxation rates (R2) with iron concentrations in postmortem brain tissue from alzheimer's disease patients

Iron accumulates in the Alzheimer's disease (AD) brain and is directly associated with β‐amyloid pathology. The proton transverse relaxation rate (R₂) has a strong linear relationship with iron concentrations in healthy brain tissue; however, an independent test of this relationship has not been extended to AD brain tissue. In this study in vitro single spin‐echo (SE) measurements were made on tissue samples from four human AD brains using a 4.7T MRI research scanner. R₂ values were calculated for 14 cortical and subcortical gray matter (GM) and white matter (WM) regions. Atomic absorption spectroscopy was used to measure iron concentrations in the corresponding excised brain regions. Significant positive linear correlations were observed between R₂ values and iron concentrations in GM regions assessed across individual tissue samples and data averaged by brain region. With the use of a predictive model for R₂, a threshold iron concentration of 55 μg Fe/g wet tissue was determined above which R₂ appears to be dominated by the affects of iron in AD brain tissue. High‐field MRI may therefore be a useful research tool for assessing brain iron changes associated with AD. Magn Reson Med 57:172–180, 2007. © 2006 Wiley‐Liss, Inc.     

In vivo measurements of irreversible and reversible transverse relaxation rates in human basal ganglia at 7 T: making inferences about the microscopic and mesoscopic structure of iron and calcification deposits

The goal of this study was to measure irreversible and reversible transverse relaxation rates in the globus pallidus and putamen at 7 T, and to use these rates to make inferences about the sub‐voxel structure of iron and calcification deposits. Gradient Echo Sampling of a Spin Echo (GESSE) data were acquired at 7 T on eighteen volunteers spanning a large range of ages (23–85 years), with calcifications in the globus pallidus incidentally observed in one volunteer. Maps of transverse relaxation rates were derived from the GESSE data, and the mean value of these rates in globus pallidus and putamen was estimated for each volunteer. Both irreversible and reversible transverse relaxation rates increased with the expected age‐dependent iron content in these structures, except for the individual with calcifications for whom extremely large reversible relaxation rates but normal irreversible relaxation rates were found in the globus pallidus. Given the sensitivity of irreversible and reversible transverse relaxation rates to microscopic and mesoscopic field variations, respectively, our findings suggest that joint consideration of these rates may yield information not only about the amount of iron and calcification deposited in the brain, but also about the sub‐voxel structure of these deposits, perhaps revealing certain aspects of their geometry and cellular distribution.     

MRI evaluation of microvascular obstruction in experimental reperfused acute myocardial infarction using a T1 and T2 preparation pulse sequence

PURPOSE: To investigate a T1 and T2 preparation pulse sequence to evaluate microvascular obstruction (MO) in a porcine model of reperfused acute myocardial infarction (AMI). MATERIALS AND METHODS: A total of 14 pigs with reperfused AMI underwent MRI examinations at baseline and three to four hours after reperfusion. MRI scans included a left ventricular functional study, T1 and T2 measurement on a 1.5T MRI system. At reperfusion, first-pass myocardial perfusion (FPMP) images were obtained after bolus injection of gadopentetate dimeglumine followed by an intravenous drip. Delayed contrast-enhanced MRI (DE-MRI) and T1 measurements were performed 30 and 45 minutes, respectively, after the bolus, during a constant infusion of gadopentetate dimeglumine. RESULTS: In 11 pigs MO was hypoenhanced in FPMP and DE-MRI. In later T1 preparation difference images postcontrast, MO was hyperenhanced while delayed hyperenhanced (DHE) regions appeared dark. MO areas on DE-MRI and T1 images were comparable. T1 reduction (%) postcontrast in MO was small compared to measurements from DHE regions (P < 0.0001) and similar to those from control segments (P = 0.66). Precontrast T1 and T2 values at reperfusion from MO and DHE regions were larger than in control regions. CONCLUSION: Using T1 preparation under a constant gadopentetate dimeglumine (Gd-DTPA) infusion, delayed imaging at 30 to 45 minutes demonstrates MO as a positive contrast with larger T1 values. Elevated T1 and T2 values in MO precontrast may also help to differentiate them from both control and DHE regions.     

On using T2 to assess extrinsic magnetic field inhomogeneity effects on T2* measurements in myocardial siderosis in thalassemia

Magnetic resonance T₂* has been validated as a noninvasive means of assessing myocardial iron overload. However, the effect on myocardial T₂* of factors such as shimming, variations in capillary geometry, and susceptibility in relation to the effects of iron has not been fully clarified. Since T₂ is not affected by extrinsic magnetic field inhomogeneity and has different sensitivity to capillary geometry, investigation into the in vivo relationship between myocardial T₂* and T₂ measurements can shed light on this important issue. This study was performed in 136 thalassemia patients. The myocardial T₂ and T₂* thresholds for normality created identical no‐iron‐overload and iron‐overloaded patient groups. In the no‐iron group, there was no correlation between myocardial T₂ and T₂*. In the iron‐overloaded patients, there was a linear correlation (R² = 0.89) between myocardial T₂* and T₂ measurements, which indicates that the iron deposition is the dominant factor in determining these two relaxation values in this scenario. Magn Reson Med, 2009. © 2008 Wiley‐Liss, Inc.     

Toward quantitative neuroimaging biomarkers for Friedreich's ataxia at 7 Tesla: Susceptibility mapping,diffusion imaging,R2 and R1 relaxometry

Friedreich's ataxia (FRDA) is a rare genetic disorder leading to degenerative processes. So far, no effective treatment has been found. Therefore, it is important to assist the development of medication with imaging biomarkers reflecting disease status and progress. Ten FRDA patients (mean age 37 ± 14 years; four female) and 10 age- and sex-matched controls were included. Acquisition of magnetic resonance imaging (MRI) data for quantitative susceptibility mapping, R₁, R₂ relaxometry and diffusion imaging was performed at 7 Tesla. Results of volume of interest (VOI)-based analyses of the quantitative data were compared with a voxel-based morphometry (VBM) evaluation. Differences between patients and controls were assessed using the analysis of covariance (ANCOVA; p < 0.01) with age and sex as covariates, effect size of group differences, and correlations with disease characteristics with Spearman correlation coefficient. For the VBM analysis, a statistical threshold of 0.001 for uncorrected and 0.05 for corrected p-values was used. Statistically significant differences between FRDA patients and controls were found in five out of twelve investigated structures, and statistically significant correlations with disease characteristics were revealed. Moreover, VBM revealed significant white matter atrophy within regions of the brainstem, and the cerebellum. These regions overlapped partially with brain regions for which significant differences between healthy controls and patients were found in the VOI-based quantitative MRI evaluation. It was shown that two independent analyses provided overlapping results. Moreover, positive results on correlations with disease characteristics were found, indicating that these quantitative MRI parameters could provide more detailed information and assist the search for effective treatments.     

New Composite Hydrogel Based on Whey and Gelatin Crosslinked with Copper Sulphate

By-products from the meat and dairy industries are important sources of high biological value proteins. This paper explores possibilities for improving the swelling and integrity of a cross-linked whey and gelatin hydrogel with different amounts of CuSO₄ × 5H₂O. Overall, swelling tests demonstrate that cross-linked samples show a better hydration capacity and stability in the hydration medium, but different copper concentrations lead to different swelling behavior. At concentrations smaller than 0.39%, the sample lasts for 75 h in a water environment before beginning to disintegrate. At a concentration of copper sulphate higher than 0.55%, the stability of the sample increased substantially. The swelling kinetics has been investigated. The diffusion constant values increased with the increase in copper concentration, but, at the highest concentration of copper (0.86%), its value has decreased. Spectroscopy analyses such as Fourier transform infrared (FT-IR), X-ray diffraction (XRD), ultraviolet-visible spectroscopy (UV-VIS), and nuclear magnetic resonance (NMR) relaxometry analyses revealed changes in the secondary and tertiary structure of proteins as a result of the interaction of Cu²⁺ ions with functional groups of protein chains. In addition to its cross-linking ability, CuSO₄ × 5H₂O has also shown excellent antibacterial properties over common bacterial strains responsible for food spoilage. The result of this research demonstrates the potential of this hydrogel system as a unique material for food packaging.     

Relaxometry model of strong dipolar perturbers for balanced-SSFP: application to quantification of SPIO loaded cells.

Magnetic resonance microscopy using magnetically labeled cells is an emerging discipline offering the potential for non-destructive studies targeting numerous cellular events in medical research. The present work develops a technique to quantify superparamagnetic iron-oxide (SPIO) loaded cells using fully balanced steady state free precession (b-SSFP) imaging. An analytic model based on phase cancellation was derived for a single particle and extended to predict mono-exponential decay versus echo time in the presence of multiple randomly distributed particles. Numerical models verified phase incoherence as the dominant contrast mechanism and evaluated the model using a full range of tissue decay rates, repetition times, and flip angles. Numerical simulations indicated a relaxation rate enhancement (DeltaR(2b)=0.412 gamma . LMD) proportional to LMD, the local magnetic dose (the additional sample magnetization due to the SPIO particles), a quantity related to the concentration of contrast agent. A phantom model of SPIO loaded cells showed excellent agreement with simulations, demonstrated comparable sensitivity to gradient echo DeltaR(*) (2) enhancements, and 14 times the sensitivity of spin echo DeltaR(2) measurements. We believe this model can be used to facilitate the generation of quantitative maps of targeted cell populations.