Diffusion Tensor Imaging of the Superior Thalamic Radiation and Cerebrospinal Fluid Distribution in Idiopathic Normal Pressure Hydrocephalus Kyan Younes, Khader M. Hasan, Arash Kamali, Christine E. McGough, Zafer Keser, Omar Hasan, Tomas Melicher, Larry A. Kramer, Paul E. Schulz, the Alzheimer’s Disease Neuroimaging Initiative Researchers From the Department of Neurology, McGovern Medical School, University of Texas Health Science Center (UTHSC), Houston, TX (KY, CEM, ZK, OH, PES); Department of Diagnostic and Interventional Imaging, McGovern Medical School, University of Texas Health Science Center (UTHSC), Houston, TX (KMH, AK, LAK); and Department of Psychiatry, McGovern Medical School, University of Texas Health Science Center (UTHSC), Houston, TX (TM). ABSTRACT BACKGROUND AND PURPOSE: Ventricular enlargement in elderly raises a challenging differential diagnosis to physicians. While Alzheimer’s disease is the most common form of dementia, idiopathic normal pressure hydrocephalus (iNPH) constitutes a potentially reversible syndrome. iNPH has a unique pathophysiology pertaining to cerebrospinal fluid (CSF) dynamics and periventricular white matter. We aimed to determine the effects of iNPH on periventricular white matter bundles and to further characterize its ventricular and sulcal CSF distribution by using diffusion tensor tractography (DTT) and CSF volumetrics on high resolution T1-weighted magnetic resonance imaging data. METHODS: Deterministic DTT and validated volumetric parcellation were performed on 20 healthy elderly, 13 Alzheimer’s disease (AD), and 9 iNPH patients. The superior thalamic radiation, corticospinal tract, and dentatorubrothalamic tract were traced and quantified using DTI studio software. Cloud-based volumetric parcellation was also performed on 138 healthy subjects across the lifespan, 13 AD, and 9 iNPH-patients. Ventricular and sulcal CSF volumes in the three groups were compared. RESULTS: Combining increased mean diffusivity of the superior thalamic radiation with ventricular volume resulted in clear separation of iNPH from the AD and age-matched healthy subject groups. Additionally, ventricular to sulcal CSF ratio, utilizing fully automated methods, was significantly greater in the iNPH patients compared to AD and healthy age-matched controls. CONCLUSIONS: Combined microstructural (DTT) and macrostructural (ventricular volume) changes is a promising radiolog- ical approach in studying ventriculomegaly. Automated estimation of the disproportionate ventricular and sulcal CSF ratio in patients presenting with ventriculomegaly may be important as radiologic markers in differentiating iNPH from other causes of ventriculomegaly. Keywords: dentatorubrothalamic tract, diffusion tensor tractography, normal pressure hydrocephalus, superior thalamic radiation, ventricular volume. Acceptance: Received May 31, 2018, and in revised form October 25, 2018. Accepted for publication October 26, 2018. Correspondence: Address correspondence to Khader M. Hasan, Department of Diagnostic and Interventional Radiology, McGovern Medical School, University of Texas, 6431 Fannin St. Houston, TX 77030. E-mail: Khader.M.Hasan@uth.tmc.edu. Acknowledgements: This study was funded in part by DUNN research foundation to KMH. We wish to thank Vipul Kumar Patel for helping in data acquisition. The Alzheimer’s disease Neuroimaging Initiative Data used in preparation of this article were obtained from the Alzheimer’s disease Neuroimaging Initiative (ADNI) database (adni.loni.usc.edu). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. A complete listing of ADNI investigators can be found at: http://adni.loni.usc.edu/wp-content/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf. Conflicts of Interest: The authors have no potential conflict of interest to disclose. J Neuroimaging 2018;00:1-10. DOI: 10.1111/jon.12581 Introduction Ventriculomegaly is a challenging neuroimaging finding neu- rologists frequently face in the aging population. 1 Hydro- cephalus is a general term that indicates accumulation of cerebrospinal fluid (CSF) in the ventricular system due to im- balance in the production, drainage, or reabsorption of CSF resulting in dilation of the cerebral ventricles. 2 It is classified into obstructive versus nonobstructive and communicating ver- sus noncommunicating hydrocephalus based on the presence or absence of an identifiable near blockage of the CSF flow and at the location of this near blockage when present, respectively. 2 If the increase in the ventricular volume (VV) is due to cerebral atrophy secondary to gray or white matter (WM) volume loss, it is called hydrocephalus ex vacuo. 1 Idiopathic normal pres- sure hydrocephalus (iNPH) is a form of chronic communicating hydrocephalus that results in a treatable syndrome character- ized by the triad of gait impairment, progressive dementia, and urinary incontinence. 3,4 iNPH prevalence is estimated to be 21.9 of 100,000 and increases with age, with an incidence of approximately 5.5 of 100,000 per year. 5 Other neurodegen- erative diseases, such as Alzheimer’s, vascular dementia, and Parkinson’s diseases, are also common in the same age pop- ulation. Studies have shown coexistence of increased rate of Alzheimer’s disease (AD) histopathology in patients with iNPH beyond what can be accounted for by chance alone. 6,7 Stud- ies have shown decrease CSF production and turnover in both ◦ C 2018 by the American Society of Neuroimaging 1