To evaluate active MS plaque evolution with conventional MRI, QSM-post processing, TSPO-PET imaging and P2X7-PET imaging.
Objective: To establish the QSM-MRI-method as a part of MS-patient research protocol in TPC and to quantify the time and space dependent correlation of QSM-MRI signal and PET-imaging signal with both 11C-PK11195 and 11C-SMW139 radioligands in the brain of MS-patients with active disease, secondary progressive MS-patients and healthy controls. Background: In MS brain the inflammatory lesions change over time from active to chronic active and finally to chronic inactive plaques. Conventional MRI-imaging is used to detect the lesions but it is not able to differentiate the plaque types. The most acute lesions with blood-brain-barrier defect can be identified using conventional MRI and gadolinium enhancing, but follow-up of the later plaque development with microglial activation at plaque edge is not possible using MRI. Furthermore, the diffuse microglial activation in the NAWM is not detectable with conventional MRI. In previous studies it has been shown that chronic active plaques have a rim of active microglial cells around them. With QSM-MRI method it is possible to detect and quantify these iron containing active microglia cells around the chronic active plaque. Active microglial cells can also be detected with PET imaging and TSPO-binding radioligand 11C-PK11195 or P2X7 binding radioligand 11C-SMW139. The investigators expect that the microglial activation signals detected with QSM-MRI and PET are co-localized and that these methods would help to differentiate the plaque types and to evaluate the MS plaque evolution. Study population: 10 MS-patients with acute gadolinium enhancing ≥0,5cm diameter lesion will be imaged at baseline and 4 and 18 months after that. For comparison 10 secondary progressive patients and 20 healthy controls will be imaged at baseline. Methods: Clinical evaluation, brain QSM-MRI and PET imaging with 11C-PK11195 radiotracer will be performed at baseline, 4 months and 18 months. PET imaging with 11C-CSMW139 radiotracer will be performed at 4 months and 18 months. For healthy controls, brain QSM-MRI, PET imaging with 11C-PK11195 radiotracer and PET imaging with 11C-SMW139 radiotracer will be performed at baseline. For 12 healthy controls a test-retest imaging with 11C-SMW139 radiotracer will be performed.
Study Type
OBSERVATIONAL
Enrollment
40
Turku PET Centre
Turku, Southwest Finland, Finland
11C-PK11195 binding in MS patient brain
Change in microglia-activity in MS patients during 18 months as measured by \[11C\]PK11195 PET imaging
Time frame: Baseline, 4 months 18 months
11C-SMW139 binding in MS patient brain
Change in microglia-activity in MS patients during 18 months as measured by \[11C\]SMW139 PET imaging
Time frame: Baseline, 4 months 18 months
QSM-signal in MS patient brain
Change in microglia-activity in MS patients during 18 months as measured by QSM-MRI
Time frame: Baseline, 4 months 18 months
11C-PK11195 binding in healthy control brain
Change in microglia-activity in healthy controls during 18 months as measured by PET imaging and \[11C\]PK11195
Time frame: Baseline
11C-SMW139 binding in healthy control brain
Change in microglia-activity in healthy controls during 18 months as measured by PET imaging \[11C\]SMW139
Time frame: Baseline
QSM-signal in healthy control brain
Change in microglia-activity in healthy controls during 18 months as measured by QSM-MRI
Time frame: Baseline
MRI metrics
To evaluate lesion load of the white matter MS plaques
Time frame: Baseline, 4 months, 18 months
EDSS
Expanded Disability Status Scale. The scale ranges from 0 to 10 in 0.5 unit increments that represent higher levels of disability.
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Time frame: Baseline, 4 months, 18 months
MSFC
Multiple Sclerosis Composite Score which consists of three assessments of walking speed, processing speed and finger dexterity. The scores are combined to provide a Z-score. Lower scores represent greater abnormality.
Time frame: Baseline, 4 months, 18 months
Fatigue severity scale
Fatigue Severity Scale is a self-reported, 9-item fatigue scale. Participants rate all 9 items on a 7-point Likert scale (1-2-3-4-5-6-7) depending on how appropriate they felt the statement applied to them over the preceding week. The total score is calculated by adding up the answer from each item and divide by 9. Lower scores indicate better outcomes. Maximum score is 7.
Time frame: Baseline, 4 months, 18 months
Modified Fatigue Impact Scale
The Modified Fatigue Impact Scale is a self-report survey that contains 21 items. Each item is rated 0-4. Higher scores indicate a greater impact of fatigue on a person's activities.
Time frame: Baseline, 4 months, 18 months