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Evidence of brain inflammation in patients with Human T Lymphotropic Virus type 1 associated myelopathy (HAM): A pilot multi modal imaging study using [11C] PBR28 PET, MR T1w and DWI.

Evidence of brain inflammation in patients with Human T Lymphotropic Virus type 1 associated myelopathy (HAM): A pilot multi modal imaging study using [11C] PBR28 PET, MR T1w and DWI.
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Dimber R, Guo Q, Bishop C, Adonis A, Buckley A, Kocsis A, Owen D, Kalk N, Newbould R, Gunn R, Rabiner E, Taylor GP,


Dimber R, Guo Q, Bishop C, Adonis A, Buckley A, Kocsis A, Owen D, Kalk N, Newbould R, Gunn R, Rabiner E, Taylor GP, (click to view)

Dimber R, Guo Q, Bishop C, Adonis A, Buckley A, Kocsis A, Owen D, Kalk N, Newbould R, Gunn R, Rabiner E, Taylor GP,

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Journal of nuclear medicine : official publication, Society of Nuclear Medicine 2016 8 25() pii

Abstract

HAM 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. Using a specific 18KDa Translocator Protein ligand, [(11)C] PBR28, T1-weighted and Diffusion Weighted magnetic resonance imaging, the brains of HTLV-1 infected patients, with and without HAM but no clinical evidence of brain involvement, were examined.

METHODS
Five subjects with HAM and two HTLV-1 asymptomatic carriers (AC) were studied. All underwent clinical neurological assessment including cognitive function and objective measures of gait, quantification of HTLV-1 proviral load in peripheral blood mononuclear cells and HLA DR expression on circulating CD8+ lymphocytes. [(11)C] PBR28 PET and MRI were performed on the same day. [(11)C]PBR28 PET total volume of distribution (VT) and distribution volume ratio (DVR) were estimated using 2-tissue compartment modelling. MRI data was processed using tools from the FMRIB Software Library (FSL) to estimate mean diffusivity (MD) and grey matter (GM) fraction changes. The results were compared with data from age matched healthy volunteers.

RESULTS
Across the whole brain the VT for the subjects with HAM (5.44±0.84) was significantly greater than those of AC (3.44±0.80). The DVR of thalamus in patients with severe and moderate HAM were higher compared to the healthy volunteers suggesting increased TSPO 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 HTLV1-infected patients compared to controls (p<0.001), whilst 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 CNS inflammation. CONCLUSION
This pilot study suggests that some patients with HAM have asymptomatic inflammation in the brain which can be detected and monitored by [(11)C]PBR28 PET together with structural and diffusion-weighted MRI.

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