title: Evidence of Brain Inflammation in Patients with Human T-Lymphotropic Virus Type 1-Associated Myelopathy (HAM): A Pilot, Multimodal Imaging Study Using 11C-PBR28 PET, MR T1-Weighted, and Diffusion-Weighted Imaging.
abstract: HTLV-1-associated myelopathy (HAM; HTLV-1 is human T-lymphotropic virus type 1) is a chronic debilitating neuroinflammatory disease with a predilection for the thoracic cord. Tissue damage is attributed to the cellular immune response to HTLV-1-infected lymphocytes. The brains of HTLV-1-infected patients, with and without HAM but no clinical evidence of brain involvement, were examined using a specific 18-kDa translocator protein ligand,11C-PBR28, and T1-weighted and diffusion-weighted MRI.
  
  
  METHODS
  Five subjects with HAM and 2 HTLV-1 asymptomatic carriers were studied. All underwent clinical neurologic assessment including cognitive function and objective measures of gait, quantification of HTLV-1 proviral load in peripheral blood mononuclear cells, and human leukocyte antigen-antigen D related expression on circulating CD8+ lymphocytes.11C-PBR28 PET and MRI were performed on the same day.11C-PBR28 PET total volume of distribution and distribution volume ratio (DVR) were estimated using 2-tissue-compartment modeling. MRI data were processed using tools from the FMRIB Software Library to estimate mean diffusivity (MD) and gray matter (GM) fraction changes. The results were compared with data from age-matched healthy volunteers.
  
  
  RESULTS
  Across the whole brain, the total volume of distribution for the subjects with HAM (5.44 ± 0.84) was significantly greater than that of asymptomatic carriers (3.44 ± 0.80). The DVR of the thalamus in patients with severe and moderate HAM was higher than that in the healthy volunteers, suggesting increased translocator protein binding (z > 4.72). Subjects with more severe myelopathy and with high DR expression on CD8+ lymphocytes had increased DVR and MD (near-significant correlation found for the right thalamus MD: P = 0.06). On the T1-weighted MRI scans, the GM fraction of the brain stem was reduced in all HTLV-1-infected patients compared with controls (P < 0.001), whereas the thalamus GM fraction was decreased in patients with HAM and correlated with the disease severity. There was no correlation between neurocognitive function and these markers of central nervous system inflammation.
  
  
  CONCLUSIONS
  This pilot study suggests that some patients with HAM have asymptomatic inflammation in the brain, which can be detected and monitored by11C-PBR28 PET together with structural and diffusion-weighted MRI.
authors: Imanova, Centre for Imaging Sciences, London, United Kingdom.
authors: Rahul
authors: R
authors: Dimber
authors: Institute of Psychiatry, King's College London, London, United Kingdom.
authors: Qi
authors: Q
authors: Guo
authors: Imanova, Centre for Imaging Sciences, London, United Kingdom.
authors: Courtney
authors: C
authors: Bishop
authors: National Centre for Human Retrovirology, St. Mary's Hospital, Imperial College Healthcare NHS Trust, London, United Kingdom.
authors: Adine
authors: A
authors: Adonis
authors: Department of Clinical Health Psychology, St. Mary's Hospital, Imperial College Healthcare NHS Trust, London, United Kingdom; and.
authors: Aisling
authors: A
authors: Buckley
authors: Department of Clinical Health Psychology, St. Mary's Hospital, Imperial College Healthcare NHS Trust, London, United Kingdom; and.
authors: Agnes
authors: A
authors: Kocsis
authors: Division of Brain Sciences, Imperial College London, London, United Kingdom.
authors: David
authors: D
authors: Owen
authors: Division of Brain Sciences, Imperial College London, London, United Kingdom.
authors: Nicola
authors: N
authors: Kalk
authors: Imanova, Centre for Imaging Sciences, London, United Kingdom.
authors: Rexford
authors: R
authors: Newbould
authors: Imanova, Centre for Imaging Sciences, London, United Kingdom.|Division of Brain Sciences, Imperial College London, London, United Kingdom.
authors: Roger N
authors: RN
authors: Gunn
authors: Imanova, Centre for Imaging Sciences, London, United Kingdom.|Institute of Psychiatry, King's College London, London, United Kingdom.
authors: Eugenii A
authors: EA
authors: Rabiner
authors: National Centre for Human Retrovirology, St. Mary's Hospital, Imperial College Healthcare NHS Trust, London, United Kingdom g.p.taylor@imperial.ac.uk.
authors: Graham P
authors: GP
authors: Taylor
mesh_terms: D000368:Aged; D038524:Diffusion Magnetic Resonance Imaging; D004660:Encephalitis / Q000150:complications* / Q000000981:diagnostic imaging*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D064847:Multimodal Imaging; D015493:Paraparesis, Tropical Spastic / Q000150:complications*; D010865:Pilot Projects; D049268:Positron-Emission Tomography; D011743:Pyrimidines
chemical_list: C526315:(methyl-(11)C)N-acetyl-N-(2-methoxybenzyl)-2-phenoxy-5-pyridinamine; D011743:Pyrimidines
keywords: DWI; HAM; HTLV1; MRI; PET; [11C] PBR28; neuroinflammation