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Serial whole-brain magnetization transfer imaging in patients with relapsing-remitting multiple sclerosis at baseline
N D Richert1, J L Ostuni, C N Bash
1Laboratory of Diagnostic Radiology Research, Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA.
Background And Purpose:
To determine whether occult disease fluctuates with macroscopic lesions during the natural history of multiple sclerosis (MS) and whether therapeutic interventions affect occult disease, we performed serial monthly magnetization transfer (MT) imaging in patients with relapsing-remitting MS in a crossover trial with interferon beta-lb.
Methods:
Serial whole-brain magnetization transfer ratios (MTRs) in eight patients with relapsing-remitting MS and in four control subjects were plotted as normalized histograms, and MTR parameters were compared with contrast-enhancing lesions and bulk white matter lesion load.
Results:
In patients with relapsing-remitting MS, the histographic peak of 0.25+/-0.01 and the histographic mean of 0.21+/-0.01 were statistically lower than corresponding values in control subjects, in whom the histographic peak was 0.27+/-0.01 and the histographic mean was 0.23+/-0.01. When histograms (with MTRs ranging from 0.0 to 0.5) were analyzed by quartiles (quartile 1 to quartile 4) based on histographic area, voxels with low MTRs in quartile 1 (0 to 0.12) increased during the baseline period and corresponded to bulk white matter lesion load. Interferon beta-lb reduced enhancing lesions by 91% and mean bulk white matter lesion load by 15%, but had no effect on MTR in this patient cohort.
Conclusion:
Occult disease in normal-appearing white matter of patients with relapsing-remitting MS measured by MTR parallels the waxing and waning pattern of enhancing lesions and bulk white matter lesion load during the baseline period. MTR is not altered by interferon beta-lb, which raises the possibility of ongoing disease in normal-appearing white matter (not detected by conventional MR sequences).
Insights
Occult multiple sclerosis (MS) disease in normal-appearing white matter fluctuates with visible lesions. Magnetization transfer ratio (MTR) imaging reveals this, but interferon beta-1b did not alter MTR in relapsing-remitting MS patients.
Area of Science:
- Neuroimaging
- Neurology
- Radiology
Background:
- Multiple sclerosis (MS) is a chronic neurological disease characterized by demyelination and axonal damage.
- Occult disease in normal-appearing white matter (NAWM) is a key feature of MS pathogenesis.
- Understanding the natural history and therapeutic impact on occult MS lesions is crucial.
Purpose of the Study:
- To investigate the fluctuation of occult MS disease in NAWM relative to macroscopic lesions.
- To assess the effect of therapeutic interventions, specifically interferon beta-1b, on occult MS disease.
- To utilize serial monthly magnetization transfer (MT) imaging for this evaluation.
Main Methods:
- Serial whole-brain magnetization transfer ratios (MTRs) were acquired monthly in 8 relapsing-remitting MS patients and 4 controls.
- MTR data were analyzed using normalized histograms and compared with contrast-enhancing lesions and white matter lesion load.
- Interferon beta-1b treatment was administered in a crossover trial design.
Main Results:
- Patients with MS exhibited statistically lower MTR peak and mean values compared to controls.
- Low MTR voxels in quartile 1 (0-0.12) increased during the baseline period, correlating with white matter lesion load.
- Interferon beta-1b reduced enhancing lesions by 91% and lesion load by 15% but did not affect MTR.
Conclusions:
- Occult MS disease in NAWM, as measured by MTR, mirrors the dynamic changes of enhancing lesions and bulk white matter lesions.
- Magnetization transfer ratio (MTR) is not altered by interferon beta-1b treatment.
- This suggests potential ongoing disease in NAWM undetectable by conventional MRI sequences.