**1. Introduction**

Huntington's disease (HD) is caused by the expansion of cytosine-adenine-guanine (CAG) repeats in the *huntingtin* gene, and the CAG repeat length is associated with an earlier disease onset [1]. About 5% of HD cases occur before the age of 21 years, which are classified as juvenile-onset Huntington's disease (JOHD) [1]. Adult-onset HD (AOHD) is characterized by involuntary movements (chorea), whereas JOHD often causes bradykinesia [1].

Patients with JOHD experience similar patterns of neurodegeneration as patients with AOHD with some distinct exceptions. Specifically, patients with JOHD have proportionally larger cerebellar volumes relative to controls, and they do not experience thinning of the motor cortex [2] as is seen in AOHD [3]. Since these brain regions are relatively spared, it has been hypothesized that they may play a compensatory role in JOHD. Additionally, both the cerebellum and motor strip play key roles in maintaining motor control, and patients with JOHD experience markedly di fferent motor symptoms compared to patients with AOHD. However, these hypotheses are based solely on volumetric data, and little is known regarding the functional activity of the neurons in these brain regions. T1 relaxation in the rotating frame (T1ρ) is a novel neuroimaging modality that allows for analysis of biochemical changes in the brain that are undetectable by existing MRI techniques. The use of a spin-locking radio-frequency field increases sensitivity to proton exchange, which is influenced by pH, glucose, glutamate, water, and proteins. T1ρ MRI has previously been used to characterize progressive changes in other neurodegenerative diseases. Specifically, cross-sectional studies have shown that patients with Alzheimer's disease have increased T1ρ relaxation times in the hippocampus compared to controls [4–7]. Similar findings of longer T1ρ relaxation times have been reported in patients with Parkinson's disease [4,8,9], bipolar disorder [10], and multiple sclerosis [11]. These studies all employed cross-sectional designs. T1ρ relaxation times were also shown to increase in the striatum of participants with premanifest patients with AOHD [12].

To the best of our knowledge, T1ρ relaxation times have never been evaluated in patients with JOHD, but may be an important biomarker for progression in this unique subset of patients with HD. Longitudinal changes in the volume of the caudate and putamen have been studied extensively in AOHD and may serve as a valid biomarker for disease progression in that patient population. However, striatal degeneration likely begins very early in life in JOHD and may not change significantly enough over time to serve as a valid biomarker of disease progression for future clinical trials. Here, we aimed to determine if T1ρ relaxation times in subcortical regions of the brain in patients with JOHD were significantly di fferent from healthy controls.

#### **2. Materials and Methods**
