The symptoms of idiopathic normal pressure hydrocephalus (iNPH) can be improved by shunt surgery, but prediction of treatment outcome is not established. We investigated changes of the corticospinal tract (CST) in iNPH before and after shunt surgery by using diffusion microstructural imaging, which infers more specific tissue properties than conventional diffusion tensor imaging. Two biophysical models were used: neurite orientation dispersion and density imaging (NODDI) and white matter tract integrity (WMTI). In both methods, the orientational coherence within the CSTs was higher in patients than in controls, and some normalization occurred after the surgery in patients, indicating axon stretching and recovery. The estimated axon density was lower in patients than in controls but remained unchanged after the surgery, suggesting its potential as a marker for irreversible neuronal damage. In a Monte-Carlo simulation that represented model axons as undulating cylinders, both NODDI and WMTI separated the effects of axon density and undulation. Thus, diffusion MRI may distinguish between reversible and irreversible microstructural changes in iNPH. Our findings constitute a step towards a quantitative image biomarker that reflects pathological process and treatment outcomes of iNPH.
Keywords: AD, axial diffusivity; AWF, axonal water fraction; Axon density; Axon undulation; CSF, cerebrospinal fluid; CST, corticospinal tract; DTI, diffusion tensor imaging; Diffusion MRI; FA, fractional anisotropy; Idiopathic normal pressure hydrocephalus; MD, mean diffusivity; NODDI, neurite orientation dispersion and density imaging; ODI, orientation dispersion index; RD, radial diffusivity; ROI, region of interest; VF, volume fraction; VOI, volume of interest; WMTI, white matter tract integrity; iNPH, idiopathic normal pressure hydrocephalus.