Associations of DTI Metrics with Structural and Cerebrovascular Disease Imaging Metrics in Idiopathic Normal Pressure Hydrocephalus

BACKGROUND AND PURPOSE: Idiopathic normal pressure hydrocephalus symptoms can be alleviated through shunt placement. However, the identification of suitable patients is often challenging despite several existing biomarkers. DTI is commonly used to assess white matter integrity, with DTI analysis along the perivascular space being a recently described, though less extensively evaluated metric. It has been proposed to monitor glymphatic (glial-lymphatic) activity in the brain, the impairment of which may play a role in several neurologic diseases. The goal of this study is to evaluate the association of DTI along the perivascular space with other diffusion and structural imaging metrics among patients with normal pressure hydrocephalus and healthy controls to provide insight into the etiology of disease-related changes in the DTI along the perivascular space metric and the utility of this metric in disease diagnosis. MATERIALS AND METHODS: This study retrospectively identified 43 patients with idiopathic normal pressure hydrocephalus patients and 86 sex and age matched controls. We compared the DTI along the perivascular space index, fractional anisotropy, ventricular volume, total intracranial volume, white matter hyperintensity volume, and perivascular space load between patients with idiopathic normal pressure hydrocephalus and controls and evaluated the association of the DTI along the perivascular space index and other imaging metrics within each diagnostic group. RESULTS: We found that the DTI analysis along the perivascular space index and fractional anisotropy were significantly lower and ventricular volume, total intracranial volume, white matter hyperintensity volume, and perivascular space load were significantly higher in idiopathic normal pressure hydrocephalus patients compared to controls. The ventricular volume, total intracranial volume, and white matter hyperintensity volume were correlated with the DTI analysis along the perivascular space index in the controls but not the patients with idiopathic normal pressure hydrocephalus. CONCLUSIONS: A lower DTI analysis along the perivascular space index in idiopathic normal pressure hydrocephalus patients may be indicative of morphological disease-related changes. The limited correlations with other imaging metrics suggest that the index is an independent or additive metric compared to existing structural or cerebrovascular disease markers of idiopathic normal pressure hydrocephalus. ABBREVIATIONS: DTI-ALPS = diffusion tensor imaging analysis along the perivascular space; iNPH = idiopathic normal pressure hydrocephalus; (C)DESH = (computation) disproportionately enlarged subarachnoid space hydrocephalus; PVS = perivascular space; WMH = white matter hyperintensity; FA = fractional anisotropy; GCC = genus of corpus callosum; AUROC = area under the receiver operating characteristic curve.