Measurement of spinal cord atrophy using phase sensitive inversion recovery (PSIR) imaging in motor neuron disease

Abstract

Background: The spectrum of motor neuron disease (MND) includes numerous phenotypes with various life expectancies. The degree of upper and lower motor neuron involvement can impact prognosis. Phase sensitive inversion recovery (PSIR) imaging has been shown to detect in vivo gray matter (GM) and white matter (WM) atrophy in the spinal cord of other patient populations but has not been explored in MND.

Methods: In this study, total cord, WM and GM areas of ten patients with a diagnosis within the MND spectrum were compared to those of ten healthy controls (HC). Patients' diagnosis included amyotrophic lateral sclerosis (ALS), primary lateral sclerosis, primary muscular atrophy, facial onset sensory and motor neuronopathy and ALS-Frontotemporal dementia. Axial 2D PSIR images were acquired at four cervical disc levels (C2-C3, C3-C4, C5-C6 and C7-T1) with a short acquisition time (2 minutes) protocol. Total cross-sectional areas (TCA), GM and WM areas were measured using a combination of highly reliable manual and semi-automated methods. Cord areas in MND patients were compared with HC using linear regression analyses adjusted for age and sex. Correlation of WM and GM areas in MND patients was explored to gain insights into underlying atrophy patterns.

Results: MND patients as a group had significantly smaller cervical cord GM area compared to HC at all four levels (C2-C3: p = .009; C3-C4: p = .001; C5-C6: p = .006; C7-T1: p = .002). WM area at C5-C6 level was significantly smaller (p = .001). TCA was significantly smaller at C3-C4 (p = .018) and C5-C6 (p = .002). No significant GM and WM atrophy was detected in the two patients with predominantly bulbar phenotype. Concomitant GM and WM atrophy was detected in solely upper or lower motor neuron level phenotypes. There was a significant correlation between GM and WM areas at all four levels in this diverse population of MND.

Conclusion: Spinal cord GM and WM atrophy can be detected in vivo in patients within the MND spectrum using a short acquisition time 2D PSIR imaging protocol. PSIR imaging shows promise as a method for quantifying spinal cord involvement and thus may be useful for diagnosis, prognosis and for monitoring disease progression.

Fig 1. Illustration of PSIR acquisition on two motor neuron disease patients.

A) Sagittal short tau inversion recovery (STIR) image used to prescribe the PSIR acquisitions at the four cervical disc levels (yellow lines). B-E) PSIR acquisitions (phase-sensitive reconstructed images are shown) of a patient with predominantly bulbar symptoms at C2-C3, C3-C4, C5-C6 and C7-T1 disc level, respectively; F-I) PSIR acquisitions of the patient with PLS at C2-C3, C3-C4, C5-C6 and C7-T1 disc level, respectively. Notice how gray and white matter are visibly reduced at all four levels in the PLS patient when compared with the patient with bulbar involvement.

Fig 2. Spinal cord gray (GM) and white matter (WM) areas of individual motor neuron disease (MND) patients.

GM and WM areas of the 10 MND patients (subject 1–10) at the four cervical levels (circles) compared to 10 healthy controls (solid line, data from Papinutto 2015[28]). Whiskers represent standard deviations.

Fig 3. Spinal cord gray (GM) and white matter (WM) areas of all 10 motor neuron disease (MND) patients and healthy controls.

Average GM (left) and WM area (right) of the 10 MND patients at the four cervical levels (circles) compared to 10 healthy controls (solid line, data from Papinutto 2015[28]). Whiskers represent standard deviations.

Fig 4. Association of gray and white matter spinal cord atrophy.

Gray matter area (x-axis) and white matter area (y-axis) for the 10 MND patients at the four cervical levels (indicated at the bottom right of each subfigure).