Guidelines for a standardized MRI protocol for MS:

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

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

Clinical Threshold Line Clinically Definite MS Clinically Isolated Syndrome Disease Onset Early “MS” (Old Terminology) Time Relapsing MS Progressive Stages

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

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

Monitoring Subclinical Disease This is what MRI is all about!

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

Subclinical Pathological Events New + Enlarging T2 Lesion Profile

From Treatment Trials to Monitoring the Individual Patient ?

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

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

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

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

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. 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) Follow-up meeting in March 2003 to update the guidelines and protocol.(19 participants)

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

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 suspected Indication for follow-up MRI in suspected MS: To establish the diagnosis of MS by detecting silent disease disseminated in time and/or space.

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.

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. established 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. established 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. Guidelines in Clinically Definite MS

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.

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

Sagittal FLAIR FLuid FLuid Attenuated Attenuated Inversion Inversion Recovery Sequences

Axial Proton Density T2 FLAIRSequences Conventional Spin Echo or Fast (Turbo) SE *

Axial (Post) Gadolinium Enhanced T1  Pre-gadolinium axial T1 scans are optional n IV Gadolinium 0.1mmol/kg (single dose) over 30 seconds  Minimum delay of 5 minutes before scanning

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

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

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

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 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) Communication An optional standardized reporting table may be helpful to the radiologist and neurologist. Comparison with previous studies (new, enlarging and/or enhancing lesions, atrophy) Interpretation and Differential diagnosis

Standardized Reporting and Charting

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. Archival & Storage

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

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

The guidelines have been presented at major international meetings