To investigate the presence and evolution of T1 relaxation time abnormalities in normal-appearing white matter (NAWM) and grey matter (GM), early in the course of relapsing–remitting multiple sclerosis (MS).
Methods
Twenty-three patients with early relapsing–remitting MS and 14 healthy controls were imaged six monthly for up to three years. Mean follow-up was 26 months for MS patients and 24 months for controls. Dual-echo fast-spin echo and gradient-echo proton-density and T1-weighted data sets (permitting the calculation of a T1 map) were acquired in all subjects. GM and NAWM T1 histograms were produced and a hierarchical regression model was used to investigate changes in T1 over time.
Results
At baseline, significant patient-control differences were seen, both in NAWM (P = 0.001) and in GM (P = 0.01). At follow-up, there was no evidence for a serial change in either mean T1 or peak-location for either NAWM or GM. There was weak evidence for a decline in patient NAWM peak-height and also evidence for a decline in control GM peak-height.
Conclusion
There are significant and persistent abnormalities of NAWM and GM T1 in early relapsing-remitting MS. Further studies should address whether such T1 measures have a role in prognosis or therapeutic monitoring.
MolyneuxPD, BarkerGJ, BarkhofF, BeckmannK, DahlkeF, FilippiM. Clinical-MRI correlations in a European trial of interferon beta-1b in secondary progressive MS.Neurology2001; 57: 2191–97.
2.
BrexPA, CiccarelliO, O'RiordanJI, SailerM, ThompsonAJ, MillerDH. A longitudinal study of abnormalities on MRI and disability from multiple sclerosis.N Engl J Med2002; 346: 158–64.
3.
BarnesD, MunroPM, YoulBD, PrineasJW, McDonaldWI. The longstanding MS lesion. A quantitative MRI and electron microscopic study.Brain1991; 114: 1271–80.
4.
BrexPA, ParkerGJ, LearySM, MolyneuxPD, BarkerGJ, DavieCA. Lesion heterogeneity in multiple sclerosis: a study of the relations between appearances on T1 weighted images, T1 relaxation times, and metabolite concentrations.J Neurol Neurosurg Psychiatry2000; 68: 627–32.
5.
van WalderveenMA, BarkhofF, PouwelsPJ, van SchijndelRA, PolmanCH, CastelijnsJA. Neuronal damage in T1-hypointense multiple sclerosis lesions demonstrated in vivo using proton magnetic resonance spectroscopy.Ann Neurol1999; 46: 79–87.
6.
HickmanSJ, BrierleyCM, SilverNC, MoseleyIF, ScoldingNJ, CompstonDA. Infratentorial hy-pointense lesion volume on T1-weighted magnetic resonance imaging correlates with disability in patients with chronic cerebellar ataxia due to multiple sclerosis.J Neurol Sci2001; 187: 35–39.
7.
AllenIV, McKeownSR. A histological, histochemical and biochemical study of the macroscopically normal white matter in multiple sclerosis.J Neurol Sci1979; 41: 81–91.
8.
EvangelouN, EsiriMM, SmithS, PalaceJ, MatthewsPM. Quantitative pathological evidence for axonal loss in normal appearing white matter in multiple sclerosis.Ann Neurol2000; 47: 391–95.
9.
FilippiM, CampiA, DoussetV, BarattiC, MartinelliV, CanalN. A magnetization transfer imaging study of normal-appearing white matter in multiple sclerosis.Neurology1995; 45: 478–82.
10.
FuL, MatthewsPM, De StefanoN, WorsleyKJ, NarayananS, FrancisGS. Imaging axonal damage of normal-appearing white matter in multiple sclerosis.Brain1998; 121: 103–13.
11.
WerringDJ, ClarkCA, BarkerGJ, ThompsonAJ, MillerDH. Diffusion tensor imaging of lesions and normal-appearing white matter in multiple sclerosis.Neurology1999; 52: 1626–32.
12.
MillerDH, JohnsonG, ToftsPS, MacManusD, McDonaldWI. Precise relaxation time measurements of normal-appearing white matter in inflammatory central nervous system disease.Magn Reson Med1989; 11: 331–36.
13.
KesselringJ, MillerDH, MacManusDG, JohnsonG, MilliganNM, ScoldingN. Quantitative magnetic resonance imaging in multiple sclerosis: the effect of high dose intravenous methylprednisolone.J Neurol Neurosurg Psychiatry1989; 52: 14–17.
14.
BarbosaS, BlumhardtLD, RobertsN, LockT, EdwardsRH. Magnetic resonance relaxation time mapping in multiple sclerosis: normal appearing white matter and the “invisible” lesion load.Magn Reson Imaging1994; 12: 33–42.
15.
HaughtonVM, YetkinFZ, RaoSM, RimmAA, FischerME, PapkeRA. Quantitative MR in the diagnosis of multiple sclerosis.Magn Reson Med1992; 26: 71–78.
16.
LarssonHB, BarkerGJ, MacKayA. Nuclear magnetic resonance relaxation in multiple sclerosis.J Neurol Neurosurg Psychiatry1998; 64: 70–76.
17.
VaithianatharL, TenchCR, MorganPS, LinX, BlumhardtLD. White matter T(1) relaxation time histograms and cerebral atrophy in multiple sclerosis.J Neurol Sci2002; 197: 45–50.
18.
GriffinCM, DehmeshkiJ, ChardDT, ParkerGJ, BarkerGJ, ThompsonAJ. T1 histograms of normal-appearing brain tissue are abnormal in early relapsing-remitting multiple sclerosis.Mult Scler2002; 8: 211–16.
19.
ParryA, ClareS, JenkinsonM, SmithS, PalaceJ, MatthewsPM. White matter and lesion T1 relaxation times increase in parallel and correlate with disability in multiple sclerosis.J Neurol2002; 249: 1279–86.
20.
ParryA, ClareS, JenkinsonM, SmithS, PalaceJ, MatthewsPM. MRI brain T1 relaxation time changes in MS patients increase over time in both the white matter and the cortex.J Neuroimaging2003; 13: 234–39.
21.
ParkerGJ, BarkerGJ, ToftsPS. Accurate multislice gradient echo T(1) measurement in the presence of non-ideal RF pulse shape and RF field nonuniformity.Magn Reson Med2001; 45: 838–45.
22.
DaviesGR, AltmannDR, HadjiprocopisA, RashidW, ChardDT, GriffinCM. Increasing normal-appearing grey and white matter magnetisation transfer ratio abnormality in early relapsing-remitting multiple sclerosis.J Neurol2005; 252: 1037–44.
23.
ChardDT, GriffinCM, RashidW, DaviesGR, AltmannDR, KapoorR. Progressive grey matter atrophy in clinically early relapsing-remitting multiple sclerosis.Mult Scler2004; 10: 387–91.
24.
TiberioM, ChardDT, AltmannDR, DaviesG, GriffinCM, RashidW. Gray and white matter volume changes in early RRMS: A 2-year longitudinal study.Neurology2005; 64: 1001–1007.
25.
TiberioM, ChardDT, AltmannDR, DaviesG, GriffinCM, McLeanMA. Metabolite changes in early relapsing-remitting multiple sclerosis: a two year follow-up study.J Neurol2006; 253: 224–30.
26.
ChardDT, GriffinCM, McLeanMA, KapellerP, KapoorR, ThompsonAJ. Brain metabolite changes in cortical grey and normal-appearing white matter in clinically early relapsing-remitting multiple sclerosis.Brain2002; 125: 2342–52.
27.
RovarisM, AgostaF, SormaniMP, IngleseM, MartinelliV, ComiG. Conventional and magnetisation transfer MRI predictors of clinical multiple sclerosis evolution: a medium-term follow-up study.Brain2003; 126: 2323–32.
28.
McFarlandHF, BarkhofF, AntelJ, MillerDH. The role of MRI as a surrogate outcome measure in multiple sclerosis.Mult Scler2002; 8: 40–51.
29.
PoserCM, PatyDW, ScheinbergL, McDonaldWI, DavisFA, EbersGC. New diagnostic criteria for multiple sclerosis: guidelines for research protocols.Ann Neurol1983; 13: 227–31.
30.
LublinFD, ReingoldSC. Defining the clinical course of multiple sclerosis: results of an international survey. National Multiple Sclerosis Society (USA) Advisory Committee on Clinical Trials of New Agents in Multiple Sclerosis.Neurology1996; 46: 907–11.
31.
KurtzkeJF. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS).Neurology1983; 33: 1444–52.
GriffinCM, ChardDT, ParkerGJ, BarkerGJ, ThompsonAJ, MillerDH. The relationship between lesion and normal appearing brain tissue abnormalities in early relapsing remitting multiple sclerosis.J Neurol2002; 249: 193–99.
38.
NaruseS, HorikawaY, TanakaC, HirakawaK, NishikawaH, YoshizakiK. Proton nuclear magnetic resonance studies on brain edema.J Neurosurg1982; 56: 747–52.
39.
BarnesD, McDonaldWI, LandonDN, JohnsonG. The characterization of experimental gliosis by quantitative nuclear magnetic resonance imaging.Brain1988; 111: 83–94.
40.
FischerHW, Van HaverbekeY, Schmitz-FeuerhakeI, MullerRN. The uncommon longitudinal relaxation dispersion of human brain white matter.Magn Reson Med1989; 9: 441–46.
41.
FischerHW, RinckPA, Van HaverbekeY, MullerRN. Nuclear relaxation of human brain gray and white matter: analysis of field dependence and implications for MRI.Magn Reson Med1990; 16: 317–34.
42.
JacksonJS, TozerDJ, ToftsPS. Measurement of subtle scanner changes using a constant temperature phantom. ESMRMB 21st Annual meeting 2004: 431.
43.
DaviesGR, Ramio-TorrentaL, HadjiprocopisA, ChardDT, GriffinCM, RashidW. Evidence for grey matter MTR abnormality in minimally disabled patients with early relapsing-remitting multiple sclerosis.J Neurol Neurosurg Psychiatry2004; 75: 998–1002.
44.
SchmiererK, ScaravilliF, AltmannDR, BarkerGJ, MillerDH. Magnetization transfer ratio and myelin in postmortem multiple sclerosis brain.Ann Neurol2004; 56: 407–15.
