Marieke van Rosmalen

Chapter 8 142 The results of our study indicate thatmotor and sensory nerves can be specific targets for pathophysiological processes in inflammatory neuropathies. We think that a widespread thickening of the peripheral nerves is likely to be caused by specific isolated changes in motor or sensory nerves in CIDP and MMN. This first study on MRI of the intraspinal roots contributes to our understanding of the pathophysiology of CIDP and MMN. Quantitative MRI of the brachial plexus MRI is a versatile tool and with adjustments of the acquisition parameters quantitative MRI data can be obtained. Innovative MRI techniques, such as diffusion tensor imaging (DTI), T2 mapping and fat fraction analysis, provide quantitative parameters ( chapter 1 ). These parameters are assumed to give information on microstructural integrity of (nervous) tissue and could contribute to our understanding of pathophysiology, for example by correlating these quantitative MRI parameters to histological findings. The basic principle is summarized in chapter 1, Figure 1.3 . Correlations of diffusion parameters with histology are mainly based on small experimental mice studies. 62,63 One study compared diffusion parameters (i.e. fractional anisotropy (FA), radial diffusivity (RD) and axial diffusivity (AD)) between shiverer mice (mouse model with myelin defects, n = 7) and control mice. 63 Histology of white matter tracts in the brain, the optic nerve and the trigeminal nerve of the shiverer mice showed a lack of myelin sheaths and DTI of these tissues showed a lower FA and a higher RD compared to the control mice, while AD did not differ. Another study evaluated RD, AD and histology of the optic nerve on four points in time in Swiss Webster mice (normal laboratory mice, n = 11) with and without retinal ischemia. 62 AD was lower in the injured nerve after three days of ischemia and remained low, while RD remained stable and started to increase after one week. Mice were sacrificed in subgroups to correlate diffusion parameters to histology at different time points. Histological analysis after three days and seven days showed axonal loss, while myelin sheets remained intact after three days but were affected after seven days. The corresponding decrease of AD after three days and increase of RD after seven days suggests that AD correlates with axonal loss and RD with demyelination. These findings were corroborated by a comparable DTI study. 64 It is a clear limitation that only a few studies are at the base of our assumption that AD and RD correlate with axonal loss and demyelination, respectively. It seems obvious that these diffusion parameters may not only reflect axonal loss and demyelination. For example, RD reflects the degree of diffusion of water perpendicular on tissue and an increase of RD might therefore also be the result of the breakdown of the axolemma or a change in its permeability, loss of neurofilaments and microtubules, axonal swelling or an increase of the extracellular space. Changes in diffusion parameters should therefore always be carefully interpreted in the pathophysiological context of the disease.

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