Quantitative susceptibility mapping (QSM) is a novel technique which allows determining the bulk magnetic susceptibility distribution of tissue in vivo from gradient echo magnetic resonance phase images. It is commonly assumed that paramagnetic iron is the predominant source of susceptibility variations in gray matter as many studies have reported a reasonable correlation of magnetic susceptibility with brain iron concentrations in vivo. Instead of performing direct comparisons, however, all these studies used the putative iron concentrations reported in the hallmark study by Hallgren and Sourander (1958) for their analysis. Consequently, the extent to which QSM can serve to reliably assess brain iron levels is not yet fully clear. To provide such information we investigated the relation between bulk tissue magnetic susceptibility and brain iron concentration in unfixed (in situ) post mortem brains of 13 subjects using MRI and inductively coupled plasma mass spectrometry. A strong linear correlation between chemically determined iron concentration and bulk magnetic susceptibility was found in gray matter structures (r = 0.84, p < 0.001), whereas the correlation coefficient was much lower in white matter (r = 0.27, p < 0.001). The slope of the overall linear correlation was consistent with theoretical considerations of the magnetism of ferritin supporting that most of the iron in the brain is bound to ferritin proteins. In conclusion, iron is the dominant source of magnetic susceptibility in deep gray matter and can be assessed with QSM. In white matter regions the estimation of iron concentrations by QSM is less accurate and more complex because the counteracting contribution from diamagnetic myelinated neuronal fibers confounds the interpretation.
Because of their strong linear correlation with iron concentration, both R2 and R2* can be used to measure iron deposition in the brain. Because R2* is more sensitive than R2 to variations in brain iron concentration and can detect differences in white matter, it is the preferred parameter for the assessment of iron concentration in vivo.
Using postmortem multislice computed tomography (MSCT) and magnetic resonance imaging (MRI), 40 forensic cases were examined and findings were verified by subsequent autopsy. Results were classified as follows: (I) cause of death, (II) relevant traumatological and pathological findings, (III) vital reactions, (IV) reconstruction of injuries, (V) visualization. In these 40 forensic cases, 47 partly combined causes of death were diagnosed at autopsy, 26 (55%) causes of death were found independently using only radiological image data. Radiology was superior to autopsy in revealing certain cases of cranial, skeletal, or tissue trauma. Some forensic vital reactions were diagnosed equally well or better using MSCT/MRI. Radiological imaging techniques are particularly beneficial for reconstruction and visualization of forensic cases, including the opportunity to use the data for expert witness reports, teaching, quality control, and telemedical consultation. These preliminary results, based on the concept of “virtopsy,” are promising enough to introduce and evaluate these radiological techniques in forensic medicine.
MR phase images have shown significantly improved contrast between cortical gray and white matter regions compared to magnitude images obtained with gradient echo sequences. A variety of underlying biophysical mechanisms (including iron, blood, myelin content, macromolecular chemical exchange, and fiber orientation) have been suggested to account for this observation but assessing the individual contribution of these factors is limited in vivo.For a closer investigation of iron and myelin induced susceptibility changes, postmortem MRI of six human corpses (age range at death: 56–80 years) was acquired in situ. Following autopsy, the iron concentrations in the frontal and occipital cortex as well as in white matter regions were chemically determined. The magnetization transfer ratio (MTR) was used as an indirect measure for myelin content. Susceptibility effects were assessed separately by determining R2* relaxation rates and quantitative phase shifts. Contributions of myelin and iron to local variations of the susceptibility were assessed by univariate and multivariate linear regression analysis.Mean iron concentration was lower in the frontal cortex than in frontal white matter (26 ± 6 vs. 45 ± 6 mg/kg wet tissue) while an inverse relation was found in the occipital lobe (cortical gray matter: 41 ± 10 vs. white matter: 34 ± 10 mg/kg wet tissue). Multiple regression analysis revealed iron and MTR as independent predictors of the effective transverse relaxation rate R2* but solely MTR was identified as source of MR phase contrast. R2* was correlated with iron concentrations in cortical gray matter only (r = 0.42, p < 0.05).In conclusion, MR phase contrast between cortical gray and white matter can be mainly attributed to variations in myelin content, but not to iron concentration. Both, myelin and iron impact the effective transverse relaxation rate R2* significantly. Magnitude contrast is limited because it only reflects the extent but not the direction of the susceptibility shift.
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