Table 1.

Advances in imaging outcomes in phase II and III clinical trials in multiple sclerosis.

Imaging technique	Imaging outcome	Treatment	Trial name	Phase	Results
RR-MS
MTI	MTR	Laquinimod	ALLEGRO	III	Significant decrease in MTR at 24 months in placebo-treated patients115
3D-T1 segmented using FIRST*	Thalamic volume	Laquinimod	ALLEGRO	III	Significant decrease in MTR at 24 months in placebo-treated patients115
1H-MRS	NAA/Cr value	Laquinimod	ALLEGRO	III	No significant change115
MTI	MTR	Peginterferon beta-1a	ADVANCE	III	Significant decrease in MTR at 24 months in placebo-treated patients122
MTI	MTR	Dimethyl fumarate	DEFINE	III	Significant decrease in MTR at 24 months in placebo-treated patients123
MTI	MTR	Dimethyl fumarate**	CONFIRM	III	No significant percent change120
MTI	MTR	IgG4 monoclonal antibody GNbAC1	CHANGE-MS	II	Significant benefits in MTR at 24 months115
PMS
MTI	MTR	Ibudilast		II	Significant decrease in MTR at 96 weeks in placebo-treated patients125
MTI	MTR	MIS416		II	NA118
3D-FLAIR postcontrast	LME	Intra-thecal rituximab		II	No changes in LME in treated patients111
NODDI	ODI; NDI	Oxcarbazepine***	PROXIMUS	II	NA118
Sodium imaging	TSC	Oxcarbazepine***	PROXIMUS	II	NA118
MTI	MTR	Amiloride, fluoxetine, riluzole	SMART	II	NA119

^*(www.fmrib.ox.ac.uk/fsl/first).

^**versus glatiramer acetate.

^***add-on to disease-modifying treatment in RR-MS converting to SP-MS.

Inclusion criteria: completed phase II and III trials in RR-MS or PMS.

Sources: https://clinicaltrials.gov; www.clinicaltrialsregister.eu.

¹H-MRS, magnetic resonance spectroscopy; 3D, three dimensional; Ig, immunoglobulin; LME, leptomeningeal contrast enhancement; MTI, magnetization transfer imaging; MTR, magnetization transfer ratio; NA, not available; NAA/Cr: N-acetyl aspartate/creatinine; NDI, neurite density index; NODDI, neurite orientation dispersion and density imaging; ODI, orientation dispersion index; PMS, progressive MS; RR-MS, relapsing–remitting MS; pRFNL, peri-papillary retinal fiber layer; SP-MS, secondary progressive MS.