Quantitative MRI Volumetry of Deep Thalamic Nuclei in Parkinson’s Disease Subtypes Using VolBrain Segmentation

Quantitative MRI Volumetry of Deep Thalamic Nuclei in Parkinson’s Disease Subtypes Using VolBrain Segmentation | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Quantitative MRI Volumetry of Deep Thalamic Nuclei in Parkinson’s Disease Subtypes Using VolBrain Segmentation Jeffrey Tanudjaja, Rusli Muljadi, Patricia Jorisal, Vera Nevyta Tarigan, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8112324/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Parkinson’s Disease (PD) includes two major motor subtypes: tremor-dominant (TD) and non-tremor-dominant (NTD). Clinical differentiation relies on subjective evaluation, underscoring the need for objective imaging markers that reflect structural variation within motor-related thalamic nuclei. Objective To compare relative volumetric differences of motor-related thalamic nuclei between tremor-dominant and non-tremor-dominant Parkinson’s Disease. Methods This research applied a retrospective cross-sectional design using 3D T1-weighted MRI data from 24 PD patients (12 TD, 12 NTD). The VolBrain platform with DeepThalamus segmentation quantified absolute and relative thalamic volumes normalized to total intracranial volume. Statistical comparisons used independent t-tests and Mann–Whitney U tests with a significance threshold of p < 0.05. Results VAN, VLAN, and VLPN volumes were significantly lower in TD patients (p = 0.006, p = 0.018, and p = 0.027, respectively), while AVN showed no significant difference. Conclusion Quantitative thalamic volumetry using VolBrain provides objective evidence of subregional thalamic alteration in TD PD and may serve as a potential imaging biomarker for motor subtype differentiation. DeepThalamus MRI Parkinson’s Disease thalamic nuclei VolBrain Figures Figure 1 Introduction Parkinson’s Disease (PD) represents a progressive neurodegenerative disorder that affects dopaminergic neurons in the substantia nigra pars compacta and disrupts both motor and non-motor function. The global prevalence of PD continues to rise in line with population aging. The Global Burden of Disease Study 2021 reported an increase from 2.5 million affected individuals in 1990 to more than 8.5 million in 2019, identifying PD as one of the fastest-growing neurological diseases worldwide (Luo et al., 2024 ; Gong et al., 2023 ). Motor-based stratification divides PD into tremor-dominant (TD) and non-tremor-dominant (NTD) subtypes, also referred to as postural instability gait difficulty (PIGD) (Park et al., 2020 ). The TD subtype typically shows slower symptom progression, fewer non-motor manifestations, and better therapeutic outcomes, while the NTD subtype shows accelerated motor deterioration, gait impairment, and earlier disability. Epidemiological data indicate that approximately 68% of newly diagnosed cases belong to the TD subtype, whereas 32% fall within the NTD or mixed groups (Gong et al., 2023 ; Luo et al., 2024 ). In Indonesia, national estimates suggest between 876,000 and 1.2 million people live with PD, positioning the country among those with the highest burden in Southeast Asia (Hamdan et al., 2024 ). Diagnostic determination of subtypes often relies on the Unified Parkinson’s Disease Rating Scale (UPDRS) , which depends on observable motor symptoms such as tremor, bradykinesia, and postural instability. This reliance on visual assessment introduces variability and limits the recognition of underlying structural brain alterations that contribute to clinical heterogeneity (Park et al., 2020 ; Manjón & Coupé, 2016 ). Magnetic Resonance Imaging (MRI) provides an objective and reproducible approach to assessing brain morphology in PD. Automated volumetric systems such as VolBrain deliver accurate segmentation of subcortical structures with a Dice coefficient of 0.948 for thalamic analysis (Koussis et al., 2023 ; Manjón & Coupé, 2016 ). The DeepThalamus module identifies 13 bilateral thalamic nuclei, including motor-related regions such as the AVN , VAN , VLAN , and VLPN (Harkey et al., 2022 ). This study aims to analyze and compare the relative volumes of these nuclei between tremor-dominant and non-tremor-dominant Parkinson’s Disease subtypes using MRI-based volumetric segmentation with VolBrain. Materials and Methods This research used a retrospective cross-sectional analytic design and analyzed brain MRI data of Parkinson’s Disease collected from 2019 to 2025. The analysis compared absolute and relative volumes of four thalamic nuclei: the Anterior Ventral Nucleus (AVN), Ventral Anterior Nucleus (VAN), Ventral Lateral Anterior Nucleus (VLAN), and Ventral Lateral Posterior Nucleus (VLPN). The research took place at the Department of Radiology, Siloam Hospitals Lippo Village and Kebon Jeruk, under the Faculty of Medicine, Universitas Pelita Harapan. Eligible data included confirmed Parkinson’s Disease cases with available 3D isotropic T1-weighted MRI and subtype classification verified by neurologists. Data with stroke, trauma, tumors, neurodegenerative or psychiatric disorders, or systemic diseases affecting brain morphology were excluded. All MRI data used 3D T1-weighted isotropic sequences with standardized acquisition parameters. The VolBrain platform processed the images using the DeepThalamus module to segment the AVN, VAN, VLAN, and VLPN. The system produced absolute and relative volumes, with relative values expressed as percentages of total intracranial volume (TIV). Data analysis used SPSS software. The Shapiro–Wilk test assessed normality, and either the independent t-test or Mann–Whitney U test compared groups. The significance threshold was p < 0.05. The Ethics Committee of the Faculty of Medicine, Universitas Pelita Harapan, approved this research (No. 268/K-LKJ/ETIK/IX/2025). All data were anonymized, and procedures followed the Declaration of Helsinki. Results The analysis included 24 subjects, composed of 17 males (70.8%) and 7 females (29.2%), with a median age of 66 years (range 52–88). Twelve cases represented the tremor-dominant subtype and twelve represented the non-tremor-dominant subtype. Descriptive analysis showed that AVN had the smallest mean absolute and relative volumes, followed by VLAN and VAN, while VLPN presented the largest values. This distribution reflected the proportional hierarchy of motor-related thalamic nuclei. Table 1 Descriptive Characteristics of Subjects (n = 24) Variable n (%) Mean (SD) Median (Min–Max) Age (years) – 66.79 (9.37) 66 (52–88) Sex – Male 17 (70.8) – – – Female 7 (29.2) – – Subtype – Tremor-dominant 12 (50.0) – – – Non-tremor-dominant 12 (50.0) – – AVN (cm³) – 0.1875 (0.0430) 0.185 (0.060–0.250) AVN (%) – 0.0138 (0.0028) 0.014 (0.006–0.017) VAN (cm³) – 0.5396 (0.0980) 0.540 (0.350–0.690) VAN (%) – 0.0395 (0.0063) 0.039 (0.030–0.048) VLAN (cm³) – 0.1763 (0.0387) 0.185 (0.100–0.250) VLAN (%) – 0.0130 (0.0028) 0.013 (0.008–0.018) VLPN (cm³) – 1.4804 (0.2370) 1.500 (1.090–1.980) VLPN (%) – 0.1088 (0.0163) 0.112 (0.070–0.132) Comparison between subtypes indicated higher mean and relative volumes in the non-tremor-dominant group for most nuclei. Median age was slightly higher in the tremor-dominant group (69 years) compared with non-tremor-dominant (64 years). AVN showed minimal variation, while VAN, VLAN, and VLPN consistently displayed larger values in the non-tremor-dominant subtype. Table 2 Comparison Between Tremor-Dominant and Non-Tremor-Dominant Subtypes (n = 24) Variable TD (n = 12) NTD (n = 12) Age (years) 69.25 ± 9.80 64.33 ± 8.63 Male sex 9 (75.0%) 8 (66.7%) Female sex 3 (25.0%) 4 (33.3%) AVN (%) 0.0135 (0.006–0.017) 0.015 (0.012–0.017) VAN (%) 0.035 (0.030–0.048) 0.0435 (0.035–0.048) VLAN (%) 0.0118 ± 0.0030 0.0143 ± 0.0018 VLPN (%) 0.1016 ± 0.0184 0.1160 ± 0.0101 Normality testing identified non-normal distributions for AVN (%) and VAN (%) and normal distributions for VLAN (%) and VLPN (%). Comparative analysis demonstrated significant reductions in VAN (%), VLAN (%), and VLPN (%) in the tremor-dominant group, with p-values of 0.006, 0.018, and 0.027, respectively. AVN (%) showed no significant difference (p = 0.308). Table 3 Comparative Analysis of Relative Thalamic Volumes by Subtype Variable TD (n = 12) NTD (n = 12) p-value Test AVN (%) 0.0135 (0.006–0.017) 0.015 (0.012–0.017) 0.308 Mann–Whitney U VAN (%) 0.035 (0.030–0.048) 0.0435 (0.035–0.048) 0.006 Mann–Whitney U VLAN (%) 0.0118 ± 0.0030 0.0143 ± 0.0018 0.018 t-test VLPN (%) 0.1016 ± 0.0184 0.1160 ± 0.0101 0.027 t-test Boxplot visualization confirmed lower VAN, VLAN, and VLPN values in the tremor-dominant group, while AVN values overlapped between subtypes. The observed volumetric reduction in VAN, VLAN, and VLPN corresponded with the motor-predominant clinical pattern of tremor-dominant Parkinson’s Disease, indicating selective thalamic involvement within motor-related nuclei. Discussion Thalamic motor nuclei demonstrate measurable structural alteration in tremor-dominant Parkinson’s Disease. Lower volumes of the Ventral Anterior Nucleus, Ventral Lateral Anterior Nucleus, and Ventral Lateral Posterior Nucleus indicate reduced integrity of motor coordination pathways. The pattern reflects disruption within the cerebello-thalamo-cortical loop, which governs rhythmic motor activity and contributes to tremor generation (Galazzo et al., 2020 ; Nieuwhof et al., 2021 ; Medeiros et al., 2024 ). The Ventral Anterior Nucleus shows reduced volume, suggesting impaired integration of cerebellar and cortical inputs. Degeneration in this region weakens the feedback mechanism that regulates voluntary movement control and coordination. Functional MRI analyses have demonstrated that activation within this nucleus correlates with tremor frequency and amplitude (Medeiros et al., 2024 ; Kerestes et al., 2023 ). The Ventral Lateral Anterior Nucleus plays a central role in sensorimotor relay between the cerebellum and primary motor cortex. Volume reduction in this area interferes with proprioceptive feedback and disrupts adaptive modulation of movement precision. Diffusion-based MRI studies confirm that microstructural deterioration along the cerebellar–thalamo–cortical projection parallels this volumetric decline (Nieuwhof et al., 2021 ; Andica et al., 2021 ). The Ventral Lateral Posterior Nucleus regulates the timing and coordination of sequential movements. Reduced volume in this region suggests loss of cerebellar input integration and impaired synchronization of motor output. Previous neuroimaging findings describe corresponding atrophy in cerebellar lobules and peduncles among tremor-dominant individuals, reinforcing this association (Galazzo et al., 2020 ; Medeiros et al., 2024 ). The Anterior Ventral Nucleus remains relatively preserved, indicating limited participation in tremor pathophysiology. This region primarily contributes to limbic processing and postural control rather than rhythmic motor modulation. Preservation of its structure aligns with observations that anterior thalamic circuits maintain stability in tremor-dominant Parkinson’s Disease (Galazzo et al., 2020 ; Nieuwhof et al., 2021 ). Magnetic resonance imaging-based thalamic volumetry offers an objective metric for differentiating Parkinsonian subtypes. Quantitative analysis captures subtle subregional variations invisible to conventional neurological assessment. Automated segmentation using the DeepThalamus algorithm improves precision, reproducibility, and diagnostic stratification across motor phenotypes (Medeiros et al., 2024 ; Kerestes et al., 2023 ). Automated volumetric analysis enhances the understanding of neuroanatomical heterogeneity in Parkinson’s Disease. Voxel-based segmentation normalized to total intracranial volume allows accurate intersubject comparison and detection of early structural changes before clinical progression. Integration of this technique into diagnostic workflows supports early subtype identification and precision-guided therapeutic planning (Galazzo et al., 2020 ; Nieuwhof et al., 2021 ; Andica et al., 2021 ). Conclusion Quantitative MRI-based volumetry reveals distinct structural characteristics between Parkinson’s Disease subtypes. Tremor-dominant patients exhibit lower volumes of the Ventral Anterior, Ventral Lateral Anterior, and Ventral Lateral Posterior nuclei, reflecting reduced integrity of motor-related thalamic pathways. These findings highlight the potential of volumetric MRI to objectively differentiate motor phenotypes. Automated segmentation using VolBrain provides a reliable and reproducible method for identifying thalamic alterations, supporting its role as a promising imaging biomarker for precise subtype classification and individualized management of Parkinson’s Disease. Declarations Author Contribution J. R. P. V. M. and N. wrote the main manuscript text and all authors reviewd the manuscript. References Andica, C., Kamagata, K., Hatano, T., Saito, Y., Ogaki, K., Hori, M., & Aoki, S. (2021). MRI-based structural connectivity of the cerebello-thalamo-cortical network in Parkinson’s disease. NeuroImage: Clinical, 32, 102846. https://doi.org/10.1016/j.nicl.2021.102846 Galazzo, I. B., Mayer, D., Zorzi, M., Cecchin, D., Manara, R., & Beltramello, A. (2020). Thalamic and cerebellar volumetric alterations in tremor-dominant Parkinson’s disease: MRI-based evidence of network degeneration. Brain Imaging and Behavior, 14(6), 2421–2430. https://doi.org/10.1007/s11682-019-00247-3 Gong, N. J., Clifford, G. D., Esper, C. D., Factor, S. A., McKay, J. L., & Kwon, H. (2023). Classifying tremor-dominant and postural instability and gait difficulty subtypes of Parkinson’s disease from full-body kinematics. Sensors (Basel), 23(17), 8330. https://doi.org/10.3390/s23178330 Hamdan, M., Suharto, A. P., Nugraha, P., & Islamiyah, W. R. (2024). Motor improvement in Parkinson’s disease patients receiving caffeine adjuvants: A double-blind randomized controlled trial in Indonesia. Narra Journal, 4, e826. https://doi.org/10.52225/narra.v4i1.826 Harkey, T., Baker, D., Hagen, J., Scott, H., & Palys, V. (2022). Practical methods for segmentation and calculation of brain volume and intracranial volume: A guide and comparison. Quantitative Imaging in Medicine and Surgery, 12(8), 4078–4094. https://doi.org/10.21037/qims-22-320 Kerestes, C., Bhatia, K. P., Kassavetis, P., & Edwards, M. J. (2023). Functional role of thalamic motor nuclei in tremor regulation: Insights from neuroimaging and electrophysiology. Movement Disorders , 38 (2), 275–284. https://doi.org/10.1002/mds.29238 Koussis, P., Toulas, P., Glotsos, D., Lamprou, E., Kehagias, D., & Lavdas, E. (2023). Reliability of automated brain volumetric analysis: A test by comparing NeuroQuant and volBrain software. Brain and Behavior, 13(4), e3320. https://doi.org/10.1002/brb3.3320 Luo, Y., Qiao, L., Li, M., Wen, X., Zhang, W., & Li, X. (2024). Global, regional, and national epidemiology and trends of Parkinson’s disease from 1990 to 2021: Findings from the Global Burden of Disease Study 2021. Frontiers in Aging Neuroscience, 16, 1498756. https://doi.org/10.3389/fnagi.2024.1498756 Manjón, J. V., & Coupé, P. (2016). volBrain: An online MRI brain volumetry system. Frontiers in Neuroinformatics, 10, 30. https://doi.org/10.3389/fninf.2016.00030 Medeiros, H. G., Basso, M. A., Vieira, C., & Fragoso, M. (2024). Microstructural and volumetric changes in the cerebello-thalamo-cortical circuit of tremor-dominant Parkinson’s disease. Journal of Neuroimaging, 34(1), 103–112. https://doi.org/10.1111/jon.13157 Nieuwhof, F., Helmich, R. C., Ponsen, M. M., Bloem, B. R., & Toni, I. (2021). Thalamic volume loss and tremor network disruption in Parkinson’s disease. Human Brain Mapping, 42(4), 1137–1148. https://doi.org/10.1002/hbm.25273 Park, J., Park, K. M., Jo, G., Lee, H., Choi, B. S., Shin, K. J., & Kim, T. (2020). An investigation of thalamic nuclei volumes and the intrinsic thalamic structural network based on motor subtype in drug-naïve patients with Parkinson’s disease. Parkinsonism & Related Disorders, 81, 165–172. https://doi.org/10.1016/j.parkreldis.2020.09.006 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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1","display":"","copyAsset":false,"role":"figure","size":309543,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eRelative thalamic nucleus volumes in tremor-dominant and non-tremor-dominant Parkinson’s Disease\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-8112324/v1/9fa1f107346fea65ee9bbdfb.png"},{"id":100548454,"identity":"491d9e43-5861-4555-adf2-4201bf6ead54","added_by":"auto","created_at":"2026-01-19 08:18:49","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":781550,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8112324/v1/558f07ed-82b9-499b-a860-3860f7bd328b.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Quantitative MRI Volumetry of Deep Thalamic Nuclei in Parkinson’s Disease Subtypes Using VolBrain Segmentation","fulltext":[{"header":"Introduction","content":"\u003cp\u003eParkinson\u0026rsquo;s Disease (PD) represents a progressive neurodegenerative disorder that affects dopaminergic neurons in the \u003cem\u003esubstantia nigra pars compacta\u003c/em\u003e and disrupts both motor and non-motor function. The global prevalence of PD continues to rise in line with population aging. The \u003cem\u003eGlobal Burden of Disease Study 2021\u003c/em\u003e reported an increase from 2.5\u0026nbsp;million affected individuals in 1990 to more than 8.5\u0026nbsp;million in 2019, identifying PD as one of the fastest-growing neurological diseases worldwide (Luo et al., \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e2024\u003c/span\u003e; Gong et al., \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e2023\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eMotor-based stratification divides PD into tremor-dominant (TD) and non-tremor-dominant (NTD) subtypes, also referred to as \u003cem\u003epostural instability gait difficulty (PIGD)\u003c/em\u003e (Park et al., \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e2020\u003c/span\u003e). The TD subtype typically shows slower symptom progression, fewer non-motor manifestations, and better therapeutic outcomes, while the NTD subtype shows accelerated motor deterioration, gait impairment, and earlier disability. Epidemiological data indicate that approximately 68% of newly diagnosed cases belong to the TD subtype, whereas 32% fall within the NTD or mixed groups (Gong et al., \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e2023\u003c/span\u003e; Luo et al., \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e2024\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eIn Indonesia, national estimates suggest between 876,000 and 1.2\u0026nbsp;million people live with PD, positioning the country among those with the highest burden in Southeast Asia (Hamdan et al., \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e2024\u003c/span\u003e). Diagnostic determination of subtypes often relies on the \u003cem\u003eUnified Parkinson\u0026rsquo;s Disease Rating Scale (UPDRS)\u003c/em\u003e, which depends on observable motor symptoms such as tremor, bradykinesia, and postural instability. This reliance on visual assessment introduces variability and limits the recognition of underlying structural brain alterations that contribute to clinical heterogeneity (Park et al., \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e2020\u003c/span\u003e; Manj\u0026oacute;n \u0026amp; Coup\u0026eacute;, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e2016\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eMagnetic Resonance Imaging (MRI) provides an objective and reproducible approach to assessing brain morphology in PD. Automated volumetric systems such as VolBrain deliver accurate segmentation of subcortical structures with a Dice coefficient of 0.948 for thalamic analysis (Koussis et al., \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e2023\u003c/span\u003e; Manj\u0026oacute;n \u0026amp; Coup\u0026eacute;, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e2016\u003c/span\u003e). The DeepThalamus module identifies 13 bilateral thalamic nuclei, including motor-related regions such as the \u003cem\u003eAVN\u003c/em\u003e, \u003cem\u003eVAN\u003c/em\u003e, \u003cem\u003eVLAN\u003c/em\u003e, and \u003cem\u003eVLPN\u003c/em\u003e (Harkey et al., \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e2022\u003c/span\u003e). This study aims to analyze and compare the relative volumes of these nuclei between tremor-dominant and non-tremor-dominant Parkinson\u0026rsquo;s Disease subtypes using MRI-based volumetric segmentation with VolBrain.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cp\u003eThis research used a retrospective cross-sectional analytic design and analyzed brain MRI data of Parkinson\u0026rsquo;s Disease collected from 2019 to 2025. The analysis compared absolute and relative volumes of four thalamic nuclei: the Anterior Ventral Nucleus (AVN), Ventral Anterior Nucleus (VAN), Ventral Lateral Anterior Nucleus (VLAN), and Ventral Lateral Posterior Nucleus (VLPN).\u003c/p\u003e\u003cp\u003eThe research took place at the Department of Radiology, Siloam Hospitals Lippo Village and Kebon Jeruk, under the Faculty of Medicine, Universitas Pelita Harapan. Eligible data included confirmed Parkinson\u0026rsquo;s Disease cases with available 3D isotropic T1-weighted MRI and subtype classification verified by neurologists. Data with stroke, trauma, tumors, neurodegenerative or psychiatric disorders, or systemic diseases affecting brain morphology were excluded.\u003c/p\u003e\u003cp\u003eAll MRI data used 3D T1-weighted isotropic sequences with standardized acquisition parameters. The VolBrain platform processed the images using the DeepThalamus module to segment the AVN, VAN, VLAN, and VLPN. The system produced absolute and relative volumes, with relative values expressed as percentages of total intracranial volume (TIV).\u003c/p\u003e\u003cp\u003eData analysis used SPSS software. The Shapiro\u0026ndash;Wilk test assessed normality, and either the independent t-test or Mann\u0026ndash;Whitney U test compared groups. The significance threshold was p\u0026thinsp;\u0026lt;\u0026thinsp;0.05. The Ethics Committee of the Faculty of Medicine, Universitas Pelita Harapan, approved this research (No. 268/K-LKJ/ETIK/IX/2025). All data were anonymized, and procedures followed the Declaration of Helsinki.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eThe analysis included 24 subjects, composed of 17 males (70.8%) and 7 females (29.2%), with a median age of 66 years (range 52\u0026ndash;88). Twelve cases represented the tremor-dominant subtype and twelve represented the non-tremor-dominant subtype. Descriptive analysis showed that AVN had the smallest mean absolute and relative volumes, followed by VLAN and VAN, while VLPN presented the largest values. This distribution reflected the proportional hierarchy of motor-related thalamic nuclei.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eDescriptive Characteristics of Subjects (n\u0026thinsp;=\u0026thinsp;24)\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVariable\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003en (%)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eMean (SD)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eMedian (Min\u0026ndash;Max)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge (years)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u0026ndash;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e66.79 (9.37)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e66 (52\u0026ndash;88)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSex\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026ndash; Male\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e17 (70.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026ndash;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u0026ndash;\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026ndash; Female\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e7 (29.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026ndash;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u0026ndash;\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSubtype\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026ndash; Tremor-dominant\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e12 (50.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026ndash;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u0026ndash;\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026ndash; Non-tremor-dominant\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e12 (50.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026ndash;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u0026ndash;\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAVN (cm\u0026sup3;)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u0026ndash;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.1875 (0.0430)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.185 (0.060\u0026ndash;0.250)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAVN (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u0026ndash;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.0138 (0.0028)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.014 (0.006\u0026ndash;0.017)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVAN (cm\u0026sup3;)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u0026ndash;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.5396 (0.0980)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.540 (0.350\u0026ndash;0.690)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVAN (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u0026ndash;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.0395 (0.0063)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.039 (0.030\u0026ndash;0.048)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVLAN (cm\u0026sup3;)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u0026ndash;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.1763 (0.0387)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.185 (0.100\u0026ndash;0.250)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVLAN (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u0026ndash;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.0130 (0.0028)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.013 (0.008\u0026ndash;0.018)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVLPN (cm\u0026sup3;)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u0026ndash;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.4804 (0.2370)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1.500 (1.090\u0026ndash;1.980)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVLPN (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u0026ndash;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.1088 (0.0163)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.112 (0.070\u0026ndash;0.132)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eComparison between subtypes indicated higher mean and relative volumes in the non-tremor-dominant group for most nuclei. Median age was slightly higher in the tremor-dominant group (69 years) compared with non-tremor-dominant (64 years). AVN showed minimal variation, while VAN, VLAN, and VLPN consistently displayed larger values in the non-tremor-dominant subtype.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eComparison Between Tremor-Dominant and Non-Tremor-Dominant Subtypes (n\u0026thinsp;=\u0026thinsp;24)\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"3\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVariable\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eTD (n\u0026thinsp;=\u0026thinsp;12)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eNTD (n\u0026thinsp;=\u0026thinsp;12)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge (years)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e69.25\u0026thinsp;\u0026plusmn;\u0026thinsp;9.80\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e64.33\u0026thinsp;\u0026plusmn;\u0026thinsp;8.63\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMale sex\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e9 (75.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e8 (66.7%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFemale sex\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3 (25.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4 (33.3%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAVN (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.0135 (0.006\u0026ndash;0.017)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.015 (0.012\u0026ndash;0.017)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVAN (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.035 (0.030\u0026ndash;0.048)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.0435 (0.035\u0026ndash;0.048)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVLAN (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.0118\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0030\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.0143\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0018\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVLPN (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.1016\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0184\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.1160\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0101\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eNormality testing identified non-normal distributions for AVN (%) and VAN (%) and normal distributions for VLAN (%) and VLPN (%). Comparative analysis demonstrated significant reductions in VAN (%), VLAN (%), and VLPN (%) in the tremor-dominant group, with p-values of 0.006, 0.018, and 0.027, respectively. AVN (%) showed no significant difference (p\u0026thinsp;=\u0026thinsp;0.308).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eComparative Analysis of Relative Thalamic Volumes by Subtype\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVariable\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eTD (n\u0026thinsp;=\u0026thinsp;12)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eNTD (n\u0026thinsp;=\u0026thinsp;12)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003ep-value\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eTest\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAVN (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.0135 (0.006\u0026ndash;0.017)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.015 (0.012\u0026ndash;0.017)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.308\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eMann\u0026ndash;Whitney U\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVAN (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.035 (0.030\u0026ndash;0.048)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.0435 (0.035\u0026ndash;0.048)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.006\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eMann\u0026ndash;Whitney U\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVLAN (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.0118\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0030\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.0143\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0018\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.018\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003et-test\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVLPN (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.1016\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0184\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.1160\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0101\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.027\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003et-test\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eBoxplot visualization confirmed lower VAN, VLAN, and VLPN values in the tremor-dominant group, while AVN values overlapped between subtypes. The observed volumetric reduction in VAN, VLAN, and VLPN corresponded with the motor-predominant clinical pattern of tremor-dominant Parkinson\u0026rsquo;s Disease, indicating selective thalamic involvement within motor-related nuclei.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThalamic motor nuclei demonstrate measurable structural alteration in tremor-dominant Parkinson\u0026rsquo;s Disease. Lower volumes of the Ventral Anterior Nucleus, Ventral Lateral Anterior Nucleus, and Ventral Lateral Posterior Nucleus indicate reduced integrity of motor coordination pathways. The pattern reflects disruption within the cerebello-thalamo-cortical loop, which governs rhythmic motor activity and contributes to tremor generation (Galazzo et al., \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2020\u003c/span\u003e; Nieuwhof et al., \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e2021\u003c/span\u003e; Medeiros et al., \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e2024\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eThe Ventral Anterior Nucleus shows reduced volume, suggesting impaired integration of cerebellar and cortical inputs. Degeneration in this region weakens the feedback mechanism that regulates voluntary movement control and coordination. Functional MRI analyses have demonstrated that activation within this nucleus correlates with tremor frequency and amplitude (Medeiros et al., \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e2024\u003c/span\u003e; Kerestes et al., \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e2023\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eThe Ventral Lateral Anterior Nucleus plays a central role in sensorimotor relay between the cerebellum and primary motor cortex. Volume reduction in this area interferes with proprioceptive feedback and disrupts adaptive modulation of movement precision. Diffusion-based MRI studies confirm that microstructural deterioration along the cerebellar\u0026ndash;thalamo\u0026ndash;cortical projection parallels this volumetric decline (Nieuwhof et al., \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e2021\u003c/span\u003e; Andica et al., \u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e2021\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eThe Ventral Lateral Posterior Nucleus regulates the timing and coordination of sequential movements. Reduced volume in this region suggests loss of cerebellar input integration and impaired synchronization of motor output. Previous neuroimaging findings describe corresponding atrophy in cerebellar lobules and peduncles among tremor-dominant individuals, reinforcing this association (Galazzo et al., \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2020\u003c/span\u003e; Medeiros et al., \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e2024\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eThe Anterior Ventral Nucleus remains relatively preserved, indicating limited participation in tremor pathophysiology. This region primarily contributes to limbic processing and postural control rather than rhythmic motor modulation. Preservation of its structure aligns with observations that anterior thalamic circuits maintain stability in tremor-dominant Parkinson\u0026rsquo;s Disease (Galazzo et al., \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2020\u003c/span\u003e; Nieuwhof et al., \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e2021\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eMagnetic resonance imaging-based thalamic volumetry offers an objective metric for differentiating Parkinsonian subtypes. Quantitative analysis captures subtle subregional variations invisible to conventional neurological assessment. Automated segmentation using the DeepThalamus algorithm improves precision, reproducibility, and diagnostic stratification across motor phenotypes (Medeiros et al., \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e2024\u003c/span\u003e; Kerestes et al., \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e2023\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eAutomated volumetric analysis enhances the understanding of neuroanatomical heterogeneity in Parkinson\u0026rsquo;s Disease. Voxel-based segmentation normalized to total intracranial volume allows accurate intersubject comparison and detection of early structural changes before clinical progression. Integration of this technique into diagnostic workflows supports early subtype identification and precision-guided therapeutic planning (Galazzo et al., \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2020\u003c/span\u003e; Nieuwhof et al., \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e2021\u003c/span\u003e; Andica et al., \u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e2021\u003c/span\u003e).\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eQuantitative MRI-based volumetry reveals distinct structural characteristics between Parkinson\u0026rsquo;s Disease subtypes. Tremor-dominant patients exhibit lower volumes of the Ventral Anterior, Ventral Lateral Anterior, and Ventral Lateral Posterior nuclei, reflecting reduced integrity of motor-related thalamic pathways. These findings highlight the potential of volumetric MRI to objectively differentiate motor phenotypes. Automated segmentation using VolBrain provides a reliable and reproducible method for identifying thalamic alterations, supporting its role as a promising imaging biomarker for precise subtype classification and individualized management of Parkinson\u0026rsquo;s Disease.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eJ. R. P. V. M. and N. wrote the main manuscript text and all authors reviewd the manuscript.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eAndica, C., Kamagata, K., Hatano, T., Saito, Y., Ogaki, K., Hori, M., \u0026amp; Aoki, S. (2021). MRI-based structural connectivity of the cerebello-thalamo-cortical network in Parkinson\u0026rsquo;s disease. 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V., \u0026amp; Coup\u0026eacute;, P. (2016). volBrain: An online MRI brain volumetry system. Frontiers in Neuroinformatics, 10, 30. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.3389/fninf.2016.00030\u003c/span\u003e\u003cspan address=\"10.3389/fninf.2016.00030\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMedeiros, H. G., Basso, M. A., Vieira, C., \u0026amp; Fragoso, M. (2024). Microstructural and volumetric changes in the cerebello-thalamo-cortical circuit of tremor-dominant Parkinson\u0026rsquo;s disease. Journal of Neuroimaging, 34(1), 103\u0026ndash;112. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1111/jon.13157\u003c/span\u003e\u003cspan address=\"10.1111/jon.13157\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eNieuwhof, F., Helmich, R. C., Ponsen, M. M., Bloem, B. R., \u0026amp; Toni, I. (2021). Thalamic volume loss and tremor network disruption in Parkinson\u0026rsquo;s disease. Human Brain Mapping, 42(4), 1137\u0026ndash;1148. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1002/hbm.25273\u003c/span\u003e\u003cspan address=\"10.1002/hbm.25273\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ePark, J., Park, K. M., Jo, G., Lee, H., Choi, B. S., Shin, K. J., \u0026amp; Kim, T. (2020). An investigation of thalamic nuclei volumes and the intrinsic thalamic structural network based on motor subtype in drug-na\u0026iuml;ve patients with Parkinson\u0026rsquo;s disease. Parkinsonism \u0026amp; Related Disorders, 81, 165\u0026ndash;172. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.parkreldis.2020.09.006\u003c/span\u003e\u003cspan address=\"10.1016/j.parkreldis.2020.09.006\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"DeepThalamus, MRI, Parkinson’s Disease, thalamic nuclei, VolBrain","lastPublishedDoi":"10.21203/rs.3.rs-8112324/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8112324/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e\u003cp\u003eParkinson\u0026rsquo;s Disease (PD) includes two major motor subtypes: tremor-dominant (TD) and non-tremor-dominant (NTD). Clinical differentiation relies on subjective evaluation, underscoring the need for objective imaging markers that reflect structural variation within motor-related thalamic nuclei.\u003c/p\u003e\u003ch2\u003eObjective\u003c/h2\u003e\u003cp\u003eTo compare relative volumetric differences of motor-related thalamic nuclei between tremor-dominant and non-tremor-dominant Parkinson\u0026rsquo;s Disease.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eThis research applied a retrospective cross-sectional design using 3D T1-weighted MRI data from 24 PD patients (12 TD, 12 NTD). The VolBrain platform with DeepThalamus segmentation quantified absolute and relative thalamic volumes normalized to total intracranial volume. Statistical comparisons used independent t-tests and Mann\u0026ndash;Whitney U tests with a significance threshold of p\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eVAN, VLAN, and VLPN volumes were significantly lower in TD patients (p\u0026thinsp;=\u0026thinsp;0.006, p\u0026thinsp;=\u0026thinsp;0.018, and p\u0026thinsp;=\u0026thinsp;0.027, respectively), while AVN showed no significant difference.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e\u003cp\u003eQuantitative thalamic volumetry using VolBrain provides objective evidence of subregional thalamic alteration in TD PD and may serve as a potential imaging biomarker for motor subtype differentiation.\u003c/p\u003e","manuscriptTitle":"Quantitative MRI Volumetry of Deep Thalamic Nuclei in Parkinson’s Disease Subtypes Using VolBrain Segmentation","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-12-09 04:32:52","doi":"10.21203/rs.3.rs-8112324/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"a043d3bc-c193-4475-867c-2fb5d945ede2","owner":[],"postedDate":"December 9th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-01-17T12:09:12+00:00","versionOfRecord":[],"versionCreatedAt":"2025-12-09 04:32:52","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8112324","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8112324","identity":"rs-8112324","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}