Quantitative Diffusion Tensor Imaging Of Multiple Sclerosis

Purpose:(1)To evaluate retrospectively quantitative diffusion tensor imaging (DTI) values of hyperintense lesions on nonenhanced T1-weighted magnetic resonance (MR) images in patients with multiple sclerosis (MS) to elucidate the degree of demyelination or remyelination associated with Tl hyperintense lesions and study their relationship to MR markers of tissue damage (brain atrophy).(2) To investigate the quantitative DTI changes of normal-appearing corpus callosum (NACC) and other normal-appearing white matter (NAWM) in patient with early MS; and elucidating the pathogenesis of the NACC by Hofer's new scheme in Relapsing-Remitting Multiple Sclerosis (RRMS).(3) The objective of our study was to detect the change of quantitative DTI values in normal-appearing white matter fiber tracts region of brainstem, limbic system, association fibers, projection fibers in the patients with RRMS.(4)The objective of our study was to evaluate the changes of quantitative diffusion tensor (DT) metrics and normalized T2-Signal Intensity (nT2-SI) values of normal-appearing cortical gray matter (CGM) and deep gray matter (DGM) in patients with Multiple Sclerosis (MS).Materials and Methods:Institutional review board approval was obtained; informed consent was waived for this HIPAA-compliant study, we retrospectively reviewed a database of clinical and MR imaging data in consecutive patients with clinically definite MS who were referred to University of Southern California(USC) medical center from Jan 1,2008, to Aug.30,2009, including 100 patients with MS and 40 healthy control subjects without evidence of MS clinically or on imaging.. We excluded patients with any of the following:(a) poor-quality MR images, (b) other major neurologic and/or systemic diseases, or (c) age older than 60 years (to avoid confounding with findings related to age-related hyperintense and age-related atrophy on MR images. All scans were performed on a 3.0 T Signa Echo-speed MRI system (General Electric, Milwaukee, USA). All patients had conventional axial spin echo T2 weighted images (TR 3000 ms, TE 30/122ms; matrix size 256×256; FOV 240 mm; slices thickness 5 mm) and T2-FLAIR(TR 8800 ms, TE 30/158 ms; matrix size 256X256; FOV 240 mm; slice thickness 5 mm). Axial T1-weighted MR images (TR=600 ms, TE=10ms, axial slices 5 mm) were also acquired pre-and 20 min post-administration of 0.3 mmol/kg Gd-DTPA. Axial DTI was then performed using pulsed gradient, spin-echo, echo-planar imaging (repetition time [TR]/echo time [TE],2000/74; matrix,256×256; field of view,240×240 mm; slices 5 mm; b=1000 s/mm2). Diffusion weighting was applied along 15 noncollinear axies. Fractional anisotropy (FA)/mean diffusivity (MD) of lesions, NAWM, NAGM were measured and differences between two groups were analyzed, and the relationship between DTI parameters and brain atrophy were investigated in this study. Analysis of variance (ANOVA) was performed for regression analysis when the dependent variable was continuous and the independent variables were nominal or continuous. The FA values of T1 hyperintense lesions was correlated with age, disease duration, and MR measures of brain atrophy (BPF and third ventricular width) by using the Pearson correlation test. All statistical analysis was performed using SPSS version 13.0 (SPSS Inc, Chicago, IL).Results:(1) At least one T1 hyperintense lesion was found in 16 patients (total, 28 lesions). hyperintense lesion on T1-weighted imaging (T1WI) had lower MD than others signal intensity lesion on T1WI but higher than normal white matter (F=3.931, P<0.001); FA (F=3.24,P<0.001) and volume ratio (VR) (F=1.664, P< 0.001) was higher in hyperintense lesion on T1WI than hypointense/isointense on T1WI but was lower than NAWM and normal white matter in controls. There was correlation between FA and VR (r=0.678; P<0.001) and inverse correlation between FA and MD (r=-0.437; P=0.02), MD and VR (r=-0.423; P=0.025) for T1 hyperintense lesion. The MD values of T1 hyperintense lesions(r=-0.304; P<0.001) and the VR values of T1 hyperintense lesions(r=0.096; P=0.042) were significantly (negative) correlated with Brain parenchymal fraction (BPF; higher BPF score); the FA values of T1 hyperintense lesions (r=-0.111; P=0.018), the MD values of T1 hyperintense lesions (r=0.379; P<0.001) and the VR values of T1 hyperintense lesions (r=-0.142; P=0.003) were significantly correlated with third ventricular width (lower width). However, the FA value of T1 hyperintense lesions was not significantly associated with BPF(r=0.083; P=0.08).(2) In comparison with controls, the patient with early MS had significantly lower FA (P<0.001) and higher MD (P<0.001) for normal-appearing corpus callosum(NACC) regions, but FA values(P=0.216) and MD values(P=0.673) in frontal and occipital regions did not show any significant difference between two group. The change of FA/MD in the entire NACC regions was correlated with the values of Evans (r=0.648, P=0.043) in patients.(3) This study indicates that 1) there was FA heterogeneity in the corpus callosum(CC) subdivisions of Hofer's new scheme in healthy volunteers and RRMS patients:FA(regionsⅤ)> FA(regionsⅠ)> FA(regionsⅣ)> FA(regionsⅡ)> FA(regionsⅢ), FA(regionsⅤ)>FA(regionsⅠ)>FA(regionsⅡ)>FA(regionsⅢ)> FA(regionsⅣ), respectively; 2) FA in the RRMS group was significantly decreased in the regionsⅡ(F=4.159,P=0.046), regionsⅢ(F=9.257,P=0.004) and regionsⅣ(F=12.234,P=0.001) of Hofer's new scheme; and 3) the FA of the regionsⅠwas relatively intact in the MS patients compared to the healthy age-matched controls (P=0.787), while the regionsⅤshowed an insignificant trend of reduced FA values (P=0.179). The decrease in FA in every of the NACC subdivisions did not correlate with BPF (P:0.086-0.969) or T2 lesion volume (P:0.127-0.658).(4) In comparison with controls, decreasing FA values in cpt/cst (L:P=0.03; R: P=0.02), icp (L:P=0.03; R:P=0.037), scp (L:P=0.036; R:P=0.041) and ml (L P=0.014; R:P=0.035), as well as increasing MD values in cpt/cst (L:P=0.004; R: P=0.046), icp (L:P=0.047; R:P=0.011), scp (L:P=0.021; R:P=0.011) and ml (L: P=0.002; R:P=0.044) were found in patients with RRMS. No significant difference of FA and MD values was found in mcp between patients with RRMS and controls (P>0.05). None of the MD or FA values in fiber tracts of the brainstem in patients with RRMS was correlated with brain parenchymal fraction (BPF) or T2 lesion volume.(5) In comparison with controls, the RRMS patients had diminished FA values in fornix bundle (F=15.605, P=0.000135), right fornix/stria terminalis bundle (F=15.772, P=0.000127) and left fornix/stria terminalis bundle(F=8.53, P=0.004); the RRMS patients had increased MD values in fornix bundle (F=13.28, P=0.0004), right fornix/stria terminalis bundle (F=7.326, P=0.008) and right stria terminalis bundle (F=10.943, P=0.002). FA and MD values in other regions of limbic system fiber bundle did not show any significant differences between two groups.(6) In comparison with controls, the RRMS patients had diminished FA values in unc(L:F=5.498, P=0.024; R:F=5.158, P=0.029),ilf(L:F=8.267, P=0.007; R:F=5.108, P=0.03), cc/ifo(L:F=5.669, P=0.022; R:F=7.162, P=0.011),ifo/ilf (L:F=4.521, P=0.04; R:F=5.437, P=0.025); the RRMS patients had diminished MD values in ilf(L:F=5.012, P=0.031; R:F=5.48, P=0.025),ifo/ilf(L:F=8.318, P=0.006; R:F=12.882, P=0.00094),cc/ifo(L:F=5.426, P=0.025; R:F=5.8, P=0.021). FA and MD values in other regions of association fiber bundle did not show any significant differences between two groups.(7) In comparison with controls, the RRMS patients had diminished FA values in ptr(L:F=12.158, P=0.001;R:F=4.401, P=0.043), cpt/atr(L:F=6.545, P=0.015;R:F=5.371, P=0.026), cpt/ptr(L:F=12.141, P=0.001;R:F=4.682, P=0.037), cpt/cst/str(L:F=8.794,P=0.005;R:F=5.446,P=0.025); the RRMS patients had diminished MD values in cpt/ptr(L:F=7.466, P=0.009;R:F=7.205, P=0.011), cpt/cst/str(L:F=2.653,P=0.02;R:F=10.36,P=0.0035). FA and MD values in other regions of Projection Fibers bundle did not show any significant differences between two groups.(8) MS patients showed larger MD/smaller FA values in CGM region compared with controls (P<0.05). However, MD/FA values were not statistical significance in the DGM between MS and healthy control group. In DGM of MS patients, a significant decrease of nT2-SI values were observed when compared to controls (P<0.05), but nT2-SI values in CGM of MS patients showed no significant decrease. In CGM, only MD values of frontal lobes in MS patients were significantly (negatively) correlated with BPF(R:P=0.009, L:P=0.036) or T2 LV (R: P=0.002, L:P=0.047). nT2-SI values in all DGM regions of MS patients were significantly correlated with BPF (r=0.282 to 0.504, P<0.05) except for the left thalamus, bilateral red nucleus. There was no correlation between nT2-SI in all DGM regions and T2 LV of MS patients.Conclusion:(1) The quantitative DTI values of T1 hyperintense MS plaques were between hypo-/isointense lesions and NAWM or normal white matter, and correlated with BPF and third ventricular width. Our results supports the notion that axonal remyelination may be the reason for T1 hyperintense lesions.(2) The quantitative DTI values (FA and MD) changes indicate that in early phase of MS there is a preferential occult injury of CC, which is likely due to the corpus callosum construction features; FA values in CC subdivisions of Hofer's new scheme may represent a rewarding strategy for understanding the subtle clinical deficits of patients with RRMS.(3) The results suggest that there may be pathology change in part of normal-appearing white matter fiber tracts region of limbic system, brainstem, association fibers, projection fibers in RRMS patients. The change of quantitative DTI values detected can help to determine the neural fiber bundle of projection fibers micro pathology change in RRMS patients sensitively.(4) In CGM, the change of quantitative DT metrics of MS patients and the association with BPF and T2 LV, suggest the existence of microstructural destruction corresponding to inflammation, demyelination, or Wallerian degeneration, but the changes of CGM were independent of the concomitant changes of BPF and T2 lesion. In DGM, a decrease of nT2-SI in MS patients and the correlation of nT2-SI values with BPF (brain atrophy), suggest excessive iron deposition related to chronic destruction. Our investigation indicates the possibility of different mechanism of pathological change in CGM and DGM.