Quantitative Analysis of Brain Edema Using Post Mortem Imaging

Brain edema is a common finding during forensic autopsies. The timely origins are threefold: Firstly, it can develop ante mortem and be a part of the cause of death. Secondly, it can arise during the agonal phase and accelerate death.
Thirdly, a post mortem fluid redistribution can appear like an edema. Beside these differences, also various brain edema types exist, with the vasogenic and cytotoxic edema being the most frequent ones. The current gold standard in post mortem assessment of brain edema is the evaluation of the macroscopically visible signs by the forensic pathologists during autopsy. Although the classification into edematous or nonedematous brain is a consensus decision of several forensic pathologists, this assessment method is subjective and depends on the experience of the raters. Thus, a quantitative and objective evaluation method would help the forensic pathologists to make decisions. This evaluation method should also be noninvasive in order to not impair further autopsy results.
This thesis contains six post mortem assessment methods for brain edema: the gold standard, a recently published mathematical formula, the normalized cerebral weight (NCW), histology, the wet-dry weight (WDW) and magnetic resonance imaging (MRI). At the beginning, the mathematical formula to classify brains as edematous or nonedematous was validated. As this method did not show reliable results compared to the gold standard, the NCW method was invented. With the NCW, account is taken for the individual skull sizes. This method reveals results as reliable as the gold standard and, additionally, has the advantage of being objective and quantitative. In several existing publications, the benefit of performing histology for the assessment of brain edema is discussed and no clear conclusion can be drawn. Thus, the use of histology was investigated in this thesis and compared to the gold standard and the NCW. The routine hematoxylin and eosin (H&E) stain did not lead to reliable results, neither compared to the validation methods, nor the interrater agreement. Another post mortem assessment method for brain edema with a long history is the WDW method. Like the histology method, this method is as well critically discussed in former publications. Applying the WDW method in this thesis yielded inconclusive results when it was compared to the gold standard and the NCW. Many studies were performed using MRI to determine brain edema or the water content in the brain. However, they were not applied in situ on human deceased yet. In this thesis, it is shown that the MRI parameters T2 and fractional anisotropy (FA) are suitable to detect brain edema as these parameters correlated significantly with the NCW. However, none of the examined MRI parameters T1, T2, T*2, FA or mean diffusivity (MD) correlated with the gold standard.
To conclude, the aim of this thesis was met by detecting the MRI parameters T2 and FA as reliable biomarkers for the post mortem assessment of brain edema. In addition, MRI offers the possibility to evaluate brain edema noninvasively,
quantitatively and objectively. However, further research will be necessary to be able to differentiate vasogenic and cytotoxic edema.