Table 1.

Quantitative spinal imaging studies in ALS, ALS, amyotrophic lateral sclerosis; ALSFRS-r, the revised ALS functional scale; FA, fractional anisotropy; CSA, cross-sectional area; CST, corticospinal tract; FVC, force vital capacity; ihMT, inhomogeneous magnetization transfer; ihMTR, inhomogeneous magnetization transfer ratio; MD, mean diffusivity; MT, magnetization transfer; MTR, magnetization transfer ratio; MMT, manual muscle testing; SC, spinal cord; SOD1, superoxide dismutase 1 gene.

Author year of publication (references)	Patient cohort n	Controls n	Spinal imaging technique	Spinal cord region evaluated	Main findings
Valsasina et al. (80)	28 Sporadic ALS	20	CSA/DTI	Cervical spinal cord	Decreased FA and CSA decreased in ALS. Strong correlation between FA and the ALSFRS and moderate correlation between spinal and brain FA
Agosta et al. (81)	17/17 at baseline/follow-up (9 months) Sporadic ALS	20	CSA/DTI	Cervical spinal cord	Longitudinal FA, MD, and CSA changes detected. Brain CST diffusivity measurements are stable over time and do not correlate with cord measures
Nair et al. (82)	14 Sporadic ALS	15	DTI	C2-C6 vertebral levels	Reduced FA and RD in ALS. FA and RD correlate with finger and foot tapping rates. RD correlates with FVC and ALSFRS-R
Carew et al. (31)	23 sporadic ALS, 24 presymptomatic SOD1carriers	29	1H-MRS	C2 vertebral level	Reduced NAA/Cr and NAA/Myo ratios in both SOD1+ and sporadic ALS. Reduced Myo/Cr in SOD1+ subjects but not in sporadic ALS. Reduced NAA/Cho in sporadic ALS but not in SOD1+ subjects
Carew et al. (83)	14 Sporadic ALS	16	1H-MRS	C2 vertebral level	Reduced NAA/Cr and NAA/Myo ratios in ALS. NAA/Myo and NAA/Cho reductions correlate with FVC
Ikeda et al. (84)	19 Sporadic ALS	20	1H-MRS	C2 vertebral level	Reduced NAA/Cr and NAA/Myo ratios in ALS. NAA/Cr and NAA/Myo correlate with ALSFRS and FVC. NAA/Cr, NAA/m-Ins, and m-Ins/Cr are markedly altered in patients with C2 denervation and neurogenic changes
Cohen-Adad et al. (69)	27 sporadic ALS, 2 SOD1-linked familial ALS	21	CSA/DTI/MT	C2-T2 vertebral levels	Altered DTI and MT metrics in the lateral and dorsal columns. FA correlates with ALSFRS-r. Segmental cord atrophy is associated with disability. FA profile of the cervical cord is suggestive of retrograde CST degeneration i.e., “dying back”
Branco et al. (70)	25 Sporadic ALS	43	CSA	C2 vertebral level	Decreased CSA in ALS. CSA correlates with disease duration, ALSFRS-r, and ALS severity scale
El Mendili et al. (73)	29 at baseline, 14 at follow-up	–	CSA/DTI/MT	C2-T2 vertebral levels	CSA correlates with MMT. At follow-up, CSA predicts upper limb ALSFSR-R subscores, and FA predicts lower limb disability. CSA and MTR decrease between baseline and follow-up
Wang et al. (85)	24 Sporadic ALS	16	DTI	C2-C4 vertebral levels	CST FA and ADC changes in ALS. No difference in FA or ADC between patients with “definite” and “probable” ALS. No correlations between DTI parameters and modified Norris or ALSFRS-r scores
Iglesias et al. (86)	21 Sporadic ALS	21	DTI	Cervical spinal cord	Abnormal DTI metrics indicate decreased integrity of ascending sensory fibers. Significant correlation between DTI metrics and the depression of the peripheral afferent volley. The combination of SEP and DTI reveals sub-clinical sensory deficits in 85% ALS patients
Rasoanandrianina et al. (58)	10 Sporadic ALS	20	CSA/DTI/MT/ihMT	Cervical spinal cord	Spinal GM and WM atrophy in ALS. GM atrophy correlates with UMN scores. FA and MTR decrease in the CST. Axial diffusivity and ihMT decreased in the CST and dorsal columns. CSA correlates with the ALSFRS-r and spinal ALSFRS-R subscores. DTI and MT/ihMT metrics correlate with disease duration and MRC scores
de Albuquerque et al. (87)	27 at baseline, 27 at follow-up 8 months apart	27	CSA/DTI	C2 vertebral level	Longitudinal reduction in CSA. Cord area reduction correlates with change in ALSFRS-r
Querin et al. (79)	49 sporadic ALS	–	CSA/DTI/MT	C2-T2 vertebral levels	Spinal MRI parameters are more predictive of survival than clinical variables (ALSFRS-R, MMT, and disease duration)
Paquin et al. (72)	27 sporadic, 2 SOD1-linked familial ALS	22	CSA	C3-C6 vertebral levels	Spinal gray matter metrics are more sensitive to discriminate ALS patients from controls than overall cord CSA. Gray matter and spinal cord CSA correlates with ALSFRS-r and MMT arm scores. ALSFRS-r prediction improves when including a combination of gray and white matter CSA
Querin et al. (76)	60 sporadic ALS	45	CSA/DTI/MT	Cervical spinal cord	Random forest classification algorithm leads to good diagnostic performance distinguishing patients with ALS from controls with a sensitivity of 88% and specificity of 85%. The highest discrimination ability was achieved by evaluating RD, followed by FA, and CSA at the C5 spinal level
Piaggio et al. (88)	23 Sporadic ALS	18	CSA	Level of the Foramen magnum	Spinal cord area at the foramen magnum is significantly lower in ALS patients than in control subjects and is significantly correlated to ALSFRS-r. Spinal cord CSA at the foramen magnum correlates with disability in ALS independently of cerebral measures
Grolez et al. (89)	40 at baseline, 40 at follow-up 3 months apart	21	SC volume	Cervical spinal cord	Longitudinal change in cervical spinal cord volume is predictive of slow vital capacity decline and is also associated with survival