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E08 Tracking the neurodegeneration pattern of the anterior thalamic radiations in HD: a focus on brain iron, white matter integrity and metabolites
  1. Montserrat Domingo Ayllón1,2,
  2. Clara Garcia-Gorro2,
  3. Saül Martinez-Horta3,4,
  4. Jesus Perez-Perez3,4,
  5. Jaime Kulisevsky3,4,
  6. Nadia Rodriguez-Dechicha5,
  7. Irene Vaquer5,
  8. Susana Subira5,
  9. Matilde Calopa6,
  10. Esteban Muñoz7,8,9,
  11. Pilar Santacruz7,
  12. Jesus Ruiz-Idiago10,
  13. Celia Mareca11,
  14. Ruth de Diego-Balaguer2,12,13,14,
  15. Estela Camara2,12
  1. 1Hospital Universitari Joan XXIII de Tarragona – Institut de Diagnòstic per la Imatge, Tarragona, Spain
  2. 2Cognition and Brain Plasticity Unit [Bellvitge Biomedical Research Institute – IDIBELL], 08097 L’Hospitalet de Llobregat, Barcelona, Spain
  3. 3Biomedical Research Institute Sant Pau (IIB-Sant Pau), Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
  4. 4CIBERNED (Center for Networked Biomedical Research on Neurodegenerative Diseases), Carlos III Institute, Madrid, Spain
  5. 5Hestia Duran i Reynals. Hospital Duran i Reynals, Hospitalet de Llobregat, Spain
  6. 6Hospital Universitari de Bellvitge, Hospitalet de Llobregat, Spain
  7. 7Hospital Clínic de Barcelona, Barcelona, Spain
  8. 8IDIBAPS (Institut d‘Investigacions Biomèdiques August Pi i Sunyer), Barcelona, Spain
  9. 9Facultat de Medicina, University of Barcelona, Barcelona, Spain
  10. 10Hospital Mare de Deu de la Mercè, Barcelona, Spain
  11. 11Universitat Autònoma de Barcelona
  12. 12Department of Cognition, Development and Educational Psychology, Universitat de Barcelona, Barcelona, Spain
  13. 13Institute of Neurosciences, Universitat de Barcelona, Barcelona, Spain
  14. 14ICREA (Catalan Institute for Research and Advanced Studies), Barcelona, Spain

Abstract

Background HD is a suitable model to monitor the whole neurodegeneration process. Huntington’s disease (HD) affects primarily the striatum, but loss of white matter (WM) integrity and iron homeostasis disruption have been also described. These anomalies together with metabolite profiles could unveil the pathophysiologic mechanisms involved.

Aims To assess the temporal and spatial progression of neurodegeneration on both anterior thalamic radiations (ATR).

Methods Thirty-one HD gene carriers and twenty-four controls underwent neuropsychological evaluation and were scanned at 3T-MRI unit. A multimodal study was conducted to measure relaxometry, diffusivity and spectroscopy as proxies of iron, WM microstructure and metabolite composition, respectively. Three statistical approaches (average, segmental, along-the-tract) were performed, with MANOVA and post-hoc Tukey test to evaluate differences among groups and Pearson test to assess correlations.

Results ATR disintegration began in premanifest individuals and progressed in extent and severity in manifest patients. WM damage was more extensive in the right ATR that could translate a higher vulnerability and showed a spatial gradient from subcortical to deep WM in favour of the dying-back hypothesis. Iron was increased in the left ATR in premanifest individuals that might uncover a dysregulated myelination or an abnormal ferritin accumulation. NAA and creatine decreased exclusively in manifest patients suggesting neuronal loss and mitochondrial dysfunction. Furthermore, imaging parameters could be used as biomarkers given their links with clinical scores.

Abstract E08 Figure 1

Relaxometry-based iron tract profiles of the anterior thalamic radiation (ATR) across participant groups. (A) Plots display the left and right mean iron level along the core fiber of the ATR at each of 33 points along the tract for controls, premanifest and manifest huntington’s disease gene-expansion carriers. (B) Illustration of the reconstruction of the ATR. The ATR subregions are deliniated (C) Differences in mean iron levels in three of the segments of the ATR between controls, premanifest and manifest huntington’s disease gene-expansion carriers. Error bars indicate standard deviations. *p-value <0.05

Abstract E08 Figure 2

Mean diffusivity tract profiles of the anterior thalamic radiation (ATR) across participant groups. (A) Plots display the left and right mean MD level along the core fiber of the ATR at each of 33 points along the tract for controls, premanifest and manifest huntington’s disease gene-expansion carriers. (B) Illustration of the reconstruction of the ATR. The ATR subregions are deliniated (C) Differences in mean MD in three of the segments of the ATR between controls, premanifest and manifest huntington’s disease gene-expansion carriers. Error bars indicate standard deviations. *p-value <0.05, **p-value <0.01. ***p-value <0.001. MD=mean diffusivity

Abstract E08 Figure 3

Concentration of metabolites in the left anterior thalamic radiation (ATR) across participant groups. (A) Differences in mean rnetabolite levels of the ATR between controls, premanifest and manifest huntington’s disease gene-expansion carriers. Error bars indicate standard deviations. Data are presented for glutamate (Glu), Myo-inositol (Ins), N-acetyl-aspartate/N-acetyl-aspartylglutamate (NAA/NAAG), Creatine/Phosphocreatine (Cr/PCr), Glycerophosphocholine/Phosphocholine (Cr/PCr) and Glutamate/Glutamine (Glx). *p-value <0.05, **p-value <0.01; (B) Magnetic resonance Spectroscopy volume of interest superimposed on a high-definition structural T1 image representing the localization of the region of interest superior white matter of the left hemisphere of a patient. Image is in radiological convention (meaning left side of the brain is in the right)

Abstract E08 Figure 4

Relationship between iron level and mean diffusivity (MD) values in the left and the right anterior thalamic radiation (ATR) in huntington’s disease gene-expansion carriers. Bivariate plot displaying the significant negative association between iron levels and MD values along the ATR tract Linear regression line is fit for each scatterplot to aid interpretation

Conclusions The complex neurodegeneration pattern of ATR in HD can help to understand the pathophysiological mechanisms underlying HD progression. The multimodal approach and along-the-tract analysis allow for a more comprehensive evaluation of neurodegeneration.

  • anterior thalamic radiation
  • Huntington’s disease
  • neurodegeneration
  • multimodal MRI
  • relaxometry
  • diffusion
  • MRI spectroscopy

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