Multimodal Imaging of MS Reveals the Smoldering Inflammation

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.

Inclusion criteria

Active MS-patients:

• Informed consent form
• At least one 0,5 cm diameter active gadolinium enhancing lesion detected lately
• Diagnosed MS-disease according to McDonald criteria

SPMS patients

• Informed consent form
• Diagnosed MS-disease according to McDonald criteria
• SPMS disease

Healthy controls:

• Informed consent form
• healthy
• age and sex matched with MS-patients in RRMS and SPMS groups

Exclusion criteria

MS-patients:

• Patients suffering from another brain disease or other autoimmune disease in addition to multiple sclerosis
• Steroid treatment 4 weeks prior to the scan
• Significant pathology in the MRI scan other than MS-related lesions
• Patients suffering from claustrophobia or panic disorder, or patients who have exhibited hypersensitivity of PET markers (practical obstacle to the scan)
• Exposure to experimental radioactivity in the last 12 months such that the dosimetry threshold would be exceeded due to participation in the study
• Age over 70

Healthy controls:

• autoimmune disease, CNS disease or other serious disease
• Steroid treatment 4 weeks prior to the scan or other regular medication
• persons suffering from claustrophobia or panic disorder, or persons who have exhibited hypersensitivity of PET markers (practical obstacle to the scan)
• Exposure to experimental radioactivity in the last 12 months such that the dosimetry threshold would be exceeded due to participation in the study
• Age over 70