**Subcortical T1-Rho MRI Abnormalities in Juvenile-Onset Huntington's Disease**

**Alexander V. Tereshchenko 1,**†**, Jordan L. Schultz 1,2,3,\*,**†**, Ansley J. Kunnath 4, Joel E. Bruss 1,2, Eric A. Epping 1, Vincent A. Magnotta 1,5 and Peg C. Nopoulos 1,3,6**


Received: 15 July 2020; Accepted: 6 August 2020; Published: 8 August 2020

**Abstract:** Huntington's disease (HD) is a fatal neurodegenerative disease caused by the expansion of cytosine-adenine-guanine (CAG) repeats in the *huntingtin* gene. An increased CAG repeat length is associated with an earlier disease onset. About 5% of HD cases occur under the age of 21 years, which are classified as juvenile-onset Huntington's disease (JOHD). Our study aims to measure subcortical metabolic abnormalities in JOHD participants. T1-Rho (T1ρ) MRI was used to compare brain regions of 13 JOHD participants and 39 controls. Region-of-interest analyses were used to assess differences in quantitative T1ρ relaxation times. We found that the mean relaxation times in the caudate (*p* < 0.001), putamen (*p* < 0.001), globus pallidus (*p* < 0.001), and thalamus (*p* < 0.001) were increased in JOHD participants compared to controls. Furthermore, increased T1ρ relaxation times in these areas were significantly associated with lower volumes amongs<sup>t</sup> participants in the JOHD group. These findings sugges<sup>t</sup> metabolic abnormalities in brain regions previously shown to degenerate in JOHD. We also analyzed the relationships between mean regional T1ρ relaxation times and Universal Huntington's Disease Rating Scale (UHDRS) scores. UHDRS was used to evaluate participants' motor function, cognitive function, behavior, and functional capacity. Mean T1ρ relaxation times in the caudate (*p* = 0.003), putamen (*p* = 0.005), globus pallidus (*p* = 0.009), and thalamus (*p* = 0.015) were directly proportional to the UHDRS score. This suggests that the T1ρ relaxation time may also predict HD-related motor deficits. Our findings sugges<sup>t</sup> that subcortical metabolic abnormalities drive the unique hypokinetic symptoms in JOHD.

**Keywords:** juvenile-onset Huntington's disease; T1-Rho; neuroimaging
