The study was approved by the local institutional review board of the Swedish Ethical Review Authority in Linköping, and all methods were performed in accordance with the relevant guidelines and regulations. Informed written consent was obtained from all patients.
Study population
Forty-three patients who were earlier enrolled in a prospective longitudinal cohort study of early Multiple Sclerosis (MS) at the Department of Neurology at the University Hospital in Linköping, Sweden, were included. Originally, forty-six patients with a clinical suspicion of MS were consecutively enrolled and examined between October 2009 and May 2015. Three patients were excluded, one due to withdrawal of consent, one due to the finding of a trigeminal schwannoma, which explained the patient's clinical findings, and one due to missing quantitative MRI data. All patients had a normal Glomerular Filtration Rate during the study. Table 2 shows details of the patient demographics.
Table 2
No. of subjects
|
43
|
Median age at inclusion (yr)
|
31 (range 21–62)
|
Sex (M/F)
|
9:34
|
MR imaging according to a standard clinical MS protocol with the addition of quantitative MRI (qMRI) before and after administration of Magnevist (gadopentate dimeglumine, 0.2 mL/kg body weight, Bayer HealthCare Pharmaceuticals) was performed at inclusion (baseline) and after one year, two years and four years.
In order to have as homogenous a group as possible, all studies used Magnevist as the contrast agent. Some of the patients had received other contrast agents before the study, and during the study when seeking emergency healthcare. However, none of the patients received another linear contrast agent during the study period (Table 1).
We have chosen six areas for our study; two areas that are most established as targets for gadolinium depositions (the dentate nuclei and globus pallidi), and additionally four areas that are often studied regarding gadolinium depositions (the thalami, pons, white matter and frontal cortex grey matter).
MR imaging acquisition
Images were acquired on a 1.5T MR imaging scanner (Achieva, Philips Healthcare, Best, the Netherlands) by using an eight-channel phased array head coil. The sequence parameters for conventional images have previously been described (9).
The quantitative sequence, QMAP (10, 11) is a multi-section, multi-echo, and multi-saturation delay qMRI technique, used with the following parameters in this study:
-
qMRI (axial): FOV 230 x 182; 43 sections; in plane resolution 1.5 x 1.5 mm; TE, 14, 28, 42, 56, 70 ms; TR 4244 ms; TI 0.0974, 0.5846, 1.8511, 4.0919 seconds; saturation flip angle 120°; scan time 6:09 minutes (11).
All images had a section thickness of 3 mm without an intersection gap. Post-contrast qMRI images were acquired approximately 15 minutes after intravenous injection of Magnevist.
Post-processing
The qMRI sequence yields quantitative maps of longitudinal relaxation rate R1 (R1 = 1/T1), transverse relaxation rate R2, and proton density (PD), which are used for measurements and to create quantitative images matching the conventional ones. The post-processing time of the raw image dataset was approximately one minute on an ordinary PC by using SyMRI Diagnostic software (SyntheticMR, Linköping, Sweden) to create quantitative maps of R1, R2, PD and synthetic T1, T2 and T2 FLAIR images.
Radiologic evaluation
Region of Interests (ROIs) were placed in the quantitative images (Fig. 3) in the area of the dentate nuclei, globus pallidi, thalami, pons, normal-appearing white matter and frontal cortex grey matter (Fig. 4). There were no MS lesions present in the areas of R1 measurements. The segmentations were performed in MeVisLab (MeVis Medical Solutions AG, Bremen, Germany) by a radiology resident (A.L.L.), supervised by an experienced neuro-radiologist (I.B.). Conventional MR images were available for reference to confirm correct ROI placement. R1 of the areas was measured in each MR study (the baseline study and the four-year control).
Statistical analysis
All statistical calculations were performed in IBM SPSS Statistics for Macintosh, Version 27.0 (IBM Corp, Armonk NY). A p-value of ≤ 0.05 was considered significant.
The R1 value from the four-year control was compared to the R1 value of the baseline study for each subject using a Paired-Samples T test, which was performed for each of the above-mentioned six areas in the brain. For areas with a significant increase of R1, an Independent-Samples T test was performed to correlate GBCA doses to the increase in R1 in these areas.