The purpose of this paper is to perform quantitative measurements of the magnetization transfer rate (Kfor) and native T1 relaxation time (T1free) in the brain tissue of normal individuals and patients with multiple sclerosis (MS) by means of multiple gradient echo acquisitions, and to correlate these measurements with the magnetization transfer ratio (MTR). Quantitative magnetization transfer imaging was performed in five normal volunteers and 12 patients with relapsing-remitting MS on a 1.5 T magnetic resonance (MR) scanner. The T1 relaxation time under magnetization transfer irradiation (T1sat) was calculated by means of fitting the signal intensity over the flip angle in several 3D spoiled gradient echo acquisitions (3 degrees , 15 degrees , 30 degrees , and 60 degrees ), while a single acquisition without MT irradiation (flip angle of 3 degrees ) was utilized to calculate the MTR. The Kfor and T1free constants were quantified on a pixel-by-pixel basis and parametric maps were reconstructed. We performed 226 measurements of Kfor, T1free, and the MTR on normal white matter (NWM) of healthy volunteers (n=50), and normal-appearing white matter (NAWM) and pathological brain areas of MS patients (n=120 and 56, respectively). Correlation coefficients between Kfor-MTR, T1free-MTR, and T1free-Kfor were calculated. Lesions were classified, according to their characteristics on T1-weighted images, into isointense (compared to white matter), mildly hypointense (showing signal intensity lower than white matter and higher than gray matter), and severely hypointense (revealing signal intensity lower than gray matter). "Dirty" white matter (DWM) corresponded to areas with diffused high signal, as identified on T2-weighted images. Strong correlation coefficients were obtained between MTR and Kfor for all lesions studied (r2=0.9, p<0.0001), for mildly hypointense plaques (r2=0.82, p<0.0001), and for DWM (r2=0.78, p=0.0007). In contrast, comparison between MTR and T1free values yielded rather low correlation coefficients for all groups assessed. In severely hypointense lesions, an excellent correlation was found between Kfor and T1free measurements (r2=0.98, p<0.0001). Strong correlations between Kfor and T1free were found for the rest of the subgroups, except for the NAWM, in which a moderate correlation was obtained (r2=0.5, p<0.0001). We conclude that Kfor and T1free measurements are feasible and may improve our understanding of the pathological brain changes that occur in MS patients.

The aim of the current study was to perform T2 relaxation time measurements in multiple sclerosis (MS) patients and correlate them with magnetization transfer ratio (MTR) measurements, in order to investigate in more detail the various histopathological changes that occur in lesions and normal-appearing white matter (NAWM). A total number of 291 measurements of MTR and T2 relaxation times were performed in 13 MS patients and 10 age-matched healthy volunteers. Measurements concerned MS plaques (105), NAWM (80), and "dirty" white matter (DWM; 30), evenly divided between the MS patients, and normal white matter (NWM; 76) in the healthy volunteers. Biexponential T2 relaxation-time analysis was performed, and also possible linearity between MTR and mean T2 relaxation times was evaluated using linear regression analysis in all subgroups. Biexponential relaxation was more pronounced in "black-hole" lesions (16.6%) and homogeneous enhancing plaques (10%), whereas DWM, NAWM, and mildly hypointense lesions presented biexponential behavior with a lower frequency(6.6, 5, and 3.1%, respectively). Non-enhancing isointense lesions and normal white matter did not reveal any biexponential behavior. Linear regression analysis between monoexponential T2 relaxation time and MTR measurements demonstrated excellent correlation for DWM( r=-0.78, p<0.0001), very good correlation for black-hole lesions( r=-0.71, p=0.002), good correlation for isointense lesions( r=-0.60, p=0.005), moderate correlation for mildly hypointense lesions( r=-0.34, p=0.007), and non-significant correlation for homogeneous enhancing plaques, NAWM, and NWM. Biexponential T2 relaxation-time behavior is seen in only very few lesions (mainly on plaques with high degree of demyelination and axonal loss). A strong correlation between MTR and monoexponential T2 values was found in regions where either inflammation or demyelination predominates; however, when both pathological conditions coexist, this linear relationship is lost.

The dynamic susceptibility contrast magnetic resonance imaging perfusion technique was used to investigate possible hemodynamic changes in normal appearing white matter and deep gray matter (DGM) of 30 patients with clinically isolated syndrome (CIS) and 30 patients with relapsing-remitting multiple sclerosis. Thirty normal volunteers were studied as controls. Cerebral blood volume, cerebral blood flow (CBF), and mean transit time values were estimated. Normalization was achieved for each subject with respect to average values of CBF and mean transit time of the hippocampi's dentate gyrus. Measurements concerned three regions of normal white matter of normal volunteers, normal appearing white matter of CIS and patients with relapsing-remitting multiple sclerosis, and DGM regions, bilaterally. All measured normal appearing white matter and DGM regions of the patients with CIS had significantly higher cerebral blood volume and mean transit time values, while averaged DGM regions had significantly lower CBF values, compared to those of normal volunteers (P < 0.001). Regarding patients with relapsing-remitting multiple sclerosis, all measured normal appearing white matter and DGM regions showed lower CBF values than those of normal volunteers and lower cerebral blood volume and CBF values compared to patients with CIS (P < 0.001). These data provide strong evidence that hemodynamic changes--affecting both white and DGM--may occur even at the earliest stage of multiple sclerosis, with CIS patients being significantly different than relapsing-remitting multiple sclerosis patients.