Studies of DTI in NAWM have revealed decreased FA and increased MD in different regions that appear normal on conventional MRI, (19,20,25,34-39) suggesting the presence of microscopic pathology beyond the resolution of conventional MRI.
A recent study (39) showed significant water diffusion changes in the normal-appearing corpus callosum (NACC) in a group of patients with early MS; however, such significant abnormalities of DTI were not observed in frontal and occipital NAWM regions.
Studies in which diffusion changes measured on DTI in NAWM have been used to precede new lesion formation indicate another clinical application of DTI in terms of studying lesion pathogenesis and natural history.
Several studies have investigated the DTI abnormalities in NAWM and NAGM and found small but widespread MD and FA changes in PP-MS as compared with healthy controls.
Their findings suggested, similarly to ours, that FA was significantly decreased in both low- and high-grade tumors as compared with NAWM, and that FA values were higher within anaplastic tumors than within low-grade lesions.
In addition, macroscopic lesions of both NAWM
and normal appearing grey matter appeared to contribute to cognitive decline in these MS patients (Rovaris et al.
After an initial study comparing an acute lesion with NAWM of one MS case, Whitney et al published a second study using several lesions from two MS cases and white matter from control cases.
23-25,29) In 1979 Allen et al described several histological abnormalities in NAWM that was defined as white matter devoid of macroscopic visible plaques.
23-25,29) The study of Graumann et al compared 12 tissue samples from NAWM of 10 MS cases, with eight white matter tissue samples from seven control cases.
31) An additional study comparing NAWM from MS cases with white matter from age-matched controls, provided evidence of dysfunctional homeostasis and changes related to immune-mediated mechanisms, supporting the concept of MS pathogenesis being a generalized process that involves the entire CNS.
Studying gene expression alterations in NAWM has identified that oligodendrocytes in MS express "anti-inflammatory" as well as "neuroprotective" signalling pathways by which they might modulate its environment possibly influencing the progression of the disease