Magnetic resonance imaging versus histological assessment for estimation of lesion volume after experimental spinal cord injury. Laboratory investigation.

OBJECT: The purpose of this study was to compare measures of lesion volume obtained by means of 1.5-T MR imaging to those obtained by the Cavalieri method, 6 weeks after experimental spinal cord injury. METHODS: Nine male Wistar rats were subjected to spinal cord injury by clip compression (50 g) at the T-4 level. Six weeks postinjury, the rats were sacrificed, and spinal cords were analyzed ex vivo for lesion volume by means of 1.5-T MR imaging and subsequently, by the Cavalieri method. In the latter method, cords were cut longitudinally in 25-microm sections and stained with solochrome cyanin for myelin. The area of the lesion was determined for each serial section, and the distance-weighted sum of all area measures was then calculated to estimate the total lesion volume. RESULTS: Bland-Altman analysis showed that the 2 methods had an acceptable level of agreement for lesion volume estimation, but the Cavalieri method was prone to an overestimation bias. The MR imaging estimates of lesion volume were greater than the Cavalieri method estimates in 3 spinal cords, but the difference between measures was within 1 standard deviation of perfect agreement in these 3 lesions, and the mean difference between measures was 18.3%. In contrast, in those lesions in which the Cavalieri method yielded larger lesion volumes (5 lesions), the difference between measures was 2 standard deviations away from perfect agreement for 2 animals and the mean difference between measures was 72.4%. CONCLUSIONS: The results illustrate that the overestimation bias of the Cavalieri method is due, in part, to artifacts produced during processing of the spinal cord tissue.

Effects of polyethylene glycol and magnesium sulfate administration on clinically relevant neurological outcomes after spinal cord injury in the rat.

The purpose of this study was to determine the long-term effects of polyethylene glycol (PEG) and magnesium sulfate (MgSO(4)) on clinically relevant motor, sensory, and autonomic outcomes after spinal cord injury (SCI). Rats were injured by clip compression (50 g; T4) and treated 15 min and 6 hr postinjury intravenously (tail vein) with PEG (1 g/kg, 30% w/w in saline; n = 11), MgSO(4) (300 mg/kg; n = 5), PEG + MgSO(4) (n = 6), or saline (n = 10). Behavioral testing lasted for 6 weeks, followed by histological analysis of the spinal cord. Both PEG and MgSO(4) resulted in enhanced locomotor recovery and lower susceptibility to neuropathic pain (mechanical allodynia) compared with saline. At 6 weeks, BBB scores were 7.3 +/- 0.2, 7.7 +/- 0.4, and 6.4 +/- 0.6 in PEG-treated, MgSO(4)-treated, and saline-treated control groups, respectively. Likewise, at 6 weeks PEG-, MgSO(4)-, and saline-treated control animals showed 3.5 +/- 0.4, 2.8 +/- 0.9, and 5.0 +/- 0.5 avoidance responses to at-level touch, respectively. PEG + MgSO(4) improved locomotor recovery and reduced pain but did not provide additional benefit compared with either treatment alone. Neither treatment, nor their combination, attenuated mean arterial pressure (MAP) increases during autonomic dysreflexia. However, saline-treated controls had significantly lower resting MAP than PEG-treated rats and tended to have lower resting MAP than MgSO(4)-treated rats 6 weeks postinjury. MgSO(4) treatment and PEG + MgSO(4) treatment resulted in significant increases in dorsal myelin sparing, and the latter resulted in significant reductions in lesion volume, compared with saline-treated controls. Furthermore, mean lesion volumes correlated negatively with the corresponding mean BBB scores and positively with the corresponding mean pain scores. In conclusion, both PEG and MgSO(4) enhanced long-term clinical outcomes after SCI.