Guidelines for a standardized MRI protocol for MS:

1. Guidelines for a standardized MRI protocol for MS:

2. Rationale for Standardized MRI Applying knowledge from population studies to understanding the individual

3. Applying knowledge from population studies to understanding the individual • Early diagnosis- “MS” • Monitoring subclinical disease • activity & extent • Monitoring treatment efficacy • Identifying factors influencing prognosis

4. Early “MS” (Old Terminology) Clinical ThresholdLine Clinically Isolated Syndrome Relapsing MS Clinically Definite MS Disease Onset Progressive Stages Time

5. Early Diagnosis of MS - New Criteria Clinically Isolated Syndrome MS Classic MS

6. Clinically Isolated Syndrome + Positive MRI Experience and Technique Determine Result Formal evaluation median 7 Formal evaluation 3mm non-gapped slices median 13 lesions For 5 mm /gapped slices median reported at 5 lesions

7. Monitoring Subclinical Disease This is what MRI is all about!

8. Most MS pathology is clinically silent • Disease activity by MRI is 5-10 fold greater than clinical activity • The reversible & irreversible accumulating BOD relatively clinically silent but may become important over time

9. Subclinical Pathological Events New + Enlarging T2 Lesion Profile

10. From Treatment Trials to Monitoring the Individual Patient ?

11. Phase III clinical trial data Counting enhancing (or new T2) lesions to monitor an individualRichert et al, 2000

12. Advantages to standardization of MRI in individuals: • Lesion detection, characterization - early diagnosis • Detecting new lesions –patient management & treatment issues • Lesion characterization - common terminology • Consistent reporting & charting of findingsover time

13. Standardized MRI Protocol PRESCRIPTIVE GUIDELINES Standardized Clinical Indications for MRI & follow-up MRI Standardized Charting of Disease Activity Standardized MRI Acquisition Standardized MRI Report Standardized Interpretation of MRI

14. CMSC MRI Guidelines Meetings • Organizing Committee: • Don Paty, Joe Frank, Pat Coyle, • David Li, Jack Simon, Jerry Wolinsky, Tony Traboulsee • Participants: • North American, NZ, and European • clinical and research MS Neurologists, Neuroradiologists and MRI Technologists • Representatives: RSNA,ASNR

15. Consensus workshop in November 2001 sponsored by the CMSC. ( 35 participants) • Two working groups: one for the clinical guidelines and one for the standardized MRI protocol. • Follow-up meeting in March 2003 to update the guidelines and protocol.(19 participants)

16. Objective for theclinical guidelines: • When should MRI be performed to diagnose and follow MS patients? • Objective for the MRI protocol: • What is a reasonable standardized clinical MRI protocol that will allow comparison between studies?

17. Guideline--Suspected MS When available, a brain MRI that meets the standardized protocol should be done as part of the initial evaluation and for diagnosis Indication for follow-up MRI in suspected MS: To establish the diagnosis of MS by detecting silent disease disseminated in time and/or space.

18. Indications for spinal MRI - 1: • If the main presenting symptoms are at the level of the spinal cord, and have not resolved, then a spinal cord MRI and brain MRI are recommended. • Indications for spinal MRI - 2: • When the brain MRI gives equivocal results, spinal MRI provides increased specificity in patients with an abnormal brain MRI or increased sensitivity in patients with a negative brain MRI.

19. Guidelines in Clinically Definite MS The baseline evaluation of a patient with established MS includes a brain MRI that meets the standardized protocol in addition to a comprehensive neurological history and examination. In the absence of clinical indications, routine follow-up MRI (at pre-defined intervals) in established MS is not validated at this time, whether the patient is on disease modifying therapy or not. Indications for follow-up MRI in established MS include: Re-assessment for initiation or modification of treatment. Unexpected clinical worsening Suspicion of a secondary diagnosis. If a follow-up MRI is to be done, it should be performed by the standardized MRI protocol and compared to previous studies.

20. Regarding the use of gadolinium: Suspected MS – recommended. If lesions are not seen on PD, T2 or flair sequences, then it may not be necessary to give gadolinium. Baseline evaluation of established MS – optional. Follow-up evaluation – optional It was generally agreed that gadolinium provides useful additional information about new, inflammatory activity.

21. Standardized MRI Methodology • 1.0 Tesla or higher • < 3 mm, no gap if possible; otherwise 5 mm, no gap

22. Sequences Sagittal FLAIR FLuidAttenuatedInversionRecovery

23. Proton Density T2 FLAIR Sequences Axial * Conventional Spin Echo or Fast (Turbo) SE

24. Axial (Post) Gadolinium Enhanced T1 • IV Gadolinium 0.1mmol/kg (single dose) over 30 seconds • Minimum delay of5 minutes before scanning • Pre-gadolinium axial T1 scans are optional

25. Sequences Sagittal FLAIR Recommended Optional Axial PD/T2 Recommended Recommended Axial FLAIR Recommended Recommended * Optional Gadoliniumenhanced T1 Recommended *Gadolinium may not be necessary if no lesions on the PD/T2 or FLAIR images Brain MRI Protocols Suspected MS Diagnosis Established MSBaseline or FU

26. Spine • Slice thickness:< 3 mm, no gap • In plane resolution:< 1mm x 1mm • No additional gadolinium required if spinal cord study immediately follows Gad-enhanced brain MRI

27. Sagittal PD/T2 Recommended Sagittal pre-Gad T1 Recommended Sagittal post-gad T1 Axial post-gad T1 Through suspicious lesions Axial T2 Helpful to confirm suspicious lesions Spinal Cord MRI Protocol Sequences For suspicious lesions

28. Communication The referring physician should indicate on the request for the standardized MRI brain and/or spinal cord protocol (in addition to appropriate clinical information) one of the following indications: • Suspected MS • Baseline evaluation of MS • Follow-up of MS

29. Communication The radiology report should use common language and include: • Description of findings (lesion number, location, size, shape, character and qualitative assessment of brain atrophy) • Comparison with previous studies (new, enlarging and/or enhancing lesions, atrophy) • Interpretation and Differential diagnosis An optional standardized reporting table may be helpful to the radiologist and neurologist.

30. Standardized Reporting and Charting

31. Archival & Storage Copies of these MRI studies should be retained permanently and be available. Studies should be stored in a standard format (example DICOM). It may be useful for patients to keep their own studies on portable digital media.

32. CMSC MRI Guidelines Implementation strategies • Presentations at local and international meetings. • Booth at annual meetings. • CME (use and interpretation training) – Web or CD based. • Manufacturer specific protocols. • Technologists web sites and newsletters. • Improved access to CMSC website. • Examples on website (lesions, subcallosal line, protocols). • Publications.

33. The guidelines will need to be updated as new information becomes available. Future

34. The guidelines have been presented at major international meetings