Update: MRI in Multiple sclerosis
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1 Nyt indenfor MS ved MR Update: MRI in Multiple sclerosis Hartwig Roman Siebner Danish Research Centre for Magnetic Resonance (DRCMR) Copenhagen University Hospital Hvidovre Dansk Radiologisk Selskabs 10. årsmøde Januar 30 th 2015
2 Use of MRI in Multiple Sclerosis Clinically Isolated Syndrome (CIS): Diagnosis, prognosis (early conversion) Multiple Sclerosis: Monitoring disease progression Inflammation: disease activity (frequency & severity of relapses), monitoring (PML), prognosis, predicting treatment response Neurodegeneration: prognosis, predicting treatment response, assessing neuroprotective effect Clinical trials (Reader centre) Stratifying study populations Primary endpoint (phase II clinical trials) Secondary endpoint (phase III clinical trials)
3 Cortical lesion morphology in MS Type I (leukocortical) spanning the grey matter white matter (GM/WM) boundary Type II (intracortical) does not involve the pial surface or GM/WM boundary Type III/IV (subpial) extends from the pial surface to various depths of the cortex without involving the WM
4 Double Inversion Recovery (DIR) MRI Two non-selective inversion pulses applied before a Turbo Spin Echo (TSE) sequence to suppress the signal from two tissues with different longitudinal relaxation times T(1) simultaneously. For brain imaging in MS, DIR is used to selectively image the gray matter (GM) by nulling the signal from white matter (WM) and cerebrospinal fluid (CSF). The main limitation of the technique remains the intrinsic low SNR due to the specific preparation of the longitudinal magnetization. 7T!!!
5 Changes in Brain Volume in Multiple Sclerosis BRAIN VOLUME INCREASE Inflammation Remyelination Gliosis Oedema Hyperhydration BRAIN VOLUME LOSS Axonal loss Demyelination Gliosis Resolution of oedema Hyperhydration Resolution of inflammation (Pseudoatrophy)
6 Use of MRI to assess tissue loss in Multiple Sclerosis Loss of brain tissue (axons / myelin / glia) => Contributes to fixed disability MR-methods used to assess disease-related atrophy: Sensitive: detection of minimal tissue loss Reproducible: Minimal variation over repeated measurements Accurate: Reliable assignment of a voxel to the correct tissue class (white and grey matter, lesion), partial volume effects Automated: Efficient, streamlined, standardized procedure Robust towards variations in image quality
7 Brain atrophy volume loss Brain atrophy is inferred from brain volume shrinkage, which is most readily measured from sequential T1-weighted scans before gadolinium administration. Segmentation-based (Voxel-based morphometry VBM) and/or registration-based analysis (SIENA) techniques are used to determine brain volume changes over time. Temporary brain volume loss due to water shifts, termed pseudoatrophy, can be observed after alcohol intake, and use of steroids and other anti-inflammatory drugs.
8 Progressive multifocal leukoencephalopathy (PML) in multiple sclerosis patients treated with natalizumab MRI: most sensitive detection and monitoring tool in the detection of PML lesions - before clinical symptoms occur and JC-Virus DNA becomes detectable in the CSF. MRI protocol for PML screening: FLAIR (highest overall sensitivity) and DWI (active and acute PML lesions). MRI phenotype of natalizumab-associated PML is rather heterogeneous and fluctuating (showing signs of inflammation and cortical GM involvement. Wattjes and Barkhof Curr Opin Neurol 2014
9 Diagnosis and monitoring of progressive multifocal leukoencephalopathy (PML) in multiple sclerosis patients treated with natalizumab MRI is the most sensitive diagnostic tool in the detection of PML lesions - before clinical symptoms occur and JCV DNA becomes detectable in the CSF. In MRI protocol for PML screening should include FLAIR (highest overall sensitivity) and DWI (depiction of active and acute PML lesions). MRI appearance of natalizumab-associated PML is rather heterogeneous and fluctuating, including signs of inflammation and showing cortical GM involvement. Wattjes and Barkhof Curr Opin Neurol 2014
10 MRI biomarkers in clinical trials: the focus is on acute inflammatory markers Clinical activity MRI activity Relapse free Disability progression free Gd+ lesion free T2 lesion free Challenge: to close the clinical-radiological gap Natalizumab treatment: Risk of progressive multifocal leukoencephalopathy (PML) caused by JC virus (JCV) activation especially in Anti-JCV pos. patients Freedom from disease activity Brain and spinal cord atrophy NAWM & NAGM microstructure (DTI,MTR,MRS) NAWM - Normal appearing white matter NAGM - Normal appearing grey matter
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