Poster No:
2441
Submission Type:
Abstract Submission
Authors:
Minhae Kim1, Angelica Sandstrom1, Aarushi Tandon1, Akila Weerasekera1, Kelly Castro-Blanco1, Shibani Mukerji2, Vitaly Napadow3, Robert Edwards4, Eva-Maria Ratai1, Marco Loggia1
Institutions:
1A.A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 2Massachusetts General Hospital, Harvard Medical School, Boston, MA, 3Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, 4Brigham and Women’s Hospital, Harvard Medical School, Boston, MA
First Author:
Minhae Kim
A.A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School
Boston, MA
Co-Author(s):
Angelica Sandstrom
A.A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School
Boston, MA
Aarushi Tandon
A.A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School
Boston, MA
Akila Weerasekera
A.A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School
Boston, MA
Kelly Castro-Blanco
A.A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School
Boston, MA
Shibani Mukerji
Massachusetts General Hospital, Harvard Medical School
Boston, MA
Vitaly Napadow
Massachusetts General Hospital, Harvard Medical School
Charlestown, MA
Eva-Maria Ratai
A.A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School
Boston, MA
Marco Loggia, PhD
A.A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School
Boston, MA
Introduction:
Approximately 38 million people worldwide live with human immunodeficiency virus (HIV). A common neurological complication of HIV and its treatment in people living with HIV (PWH) is HIV-associated sensory neuropathy, with neuropathic pain being its most highly prevalent and debilitating symptom. Our group has previously observed elevated levels of the 18kDa translocator protein (TSPO), a marker of glial activation and neuroinflammation, in human chronic pain and HIV using [11C]PBR28 positron emission tomography (PET) [1-2]. In this study, we used [11C]PBR28 PET to evaluate the hypothesis that HIV-related neuropathic pain is accompanied by elevated levels of TSPO expression in PWH.
Methods:
Twenty-six PWH (11 with neuropathic pain, PWHpain; 15 without pain, PWHnopain) and 27 healthy controls (HC) completed [11C]PBR28 PET/MRI scans. All participants were genotyped for the Ala147Thr polymorphism in the TSPO gene, which predicts binding affinity to [11C]PBR28, and low affinity binders were considered ineligible. All PWH were on stable antiretroviral therapy and virally suppressed (plasma HIV RNA <200 copies/mL) at the time of screening. PWH completed the PainDETECT self-reported questionnaire, where higher scores (range: 0-38) indicate higher levels of neuropathic pain. Standardized uptake values (SUV) were computed from 60-90 min post-[11C]PBR28 injection data, spatially smoothed (FWHM=8mm), and normalized to the MNI template using FSL and FreeSurfer. A T1-weighted volume (MEMPRAGE; TR/TE1/TE2/TE3/TE4=2530/1.64/3.5/5.36/7.22ms, flip angle=7º, voxel size=1x1x1mm3) was used for attenuation correction of PET data and spatial normalization to the MNI space. Whole-brain voxel-wise analyses were run with Randomize, using a cluster-forming threshold of z=2.3 and including genotype as a covariate of no interest. PHW vs. HC comparison utilized occipital lobe normalization to increase sensitivity to widespread [11C]PBR28 signal, while within-PWH comparisons and correlation utilized whole brain normalization to detect regionally specific pain-related neuroinflammatory signals.
Results:
PWH showed elevated TSPO expression compared to HC in the frontal white and grey matter including the ventrolateral, ventromedial, and dorsolateral prefrontal cortices, frontal pole, and secondary somatosensory cortex. PWHpain showed higher TSPO expression compared to PWHnopain in the anterior and posterior midcingulate (aMCC and pMCC, respectively) and posterior cingulate cortices, dorsolateral and dorsomedial prefrontal cortices (dLPFC and dMPFC, respectively), precentral gyrus, superior parietal lobule (SPL), supplementary motor area (SMA), and primary somatosensory and motor cortices (S1 and M1, respectively). In PWH, TSPO expression was positively correlated with PainDETECT scores in the cuneus, aMCC, pMCC, SMA, dMPFC, dLPFC, SPL, S1 and M1.
Conclusions:
Overall, PWH showed elevated TSPO expression compared to HC, and PWHpain showed elevated [11C]PBR28 signal in the cingulate and prefrontal cortices and somatosensory and sensorimotor areas compared to PWHnopain. In PWH, [11C]PBR28 signal was positively correlated with PainDETECT scores in the prefrontal, cingulate, and primary somatosensory and motor cortices, suggesting an association between neuropathic pain and neuroinflammation. Future research with a larger sample size is required to assess the generalizability and validity of these observations.
Disorders of the Nervous System:
Neurodegenerative/ Late Life (eg. Parkinson’s, Alzheimer’s)
Novel Imaging Acquisition Methods:
PET 1
Physiology, Metabolism and Neurotransmission :
Physiology, Metabolism and Neurotransmission Other 2
Keywords:
Astrocyte
Glia
Infections
MRI
Pain
Positron Emission Tomography (PET)
1|2Indicates the priority used for review
Provide references using author date format
[1] Loggia et al. (2015). Evidence for brain glial activation in chronic pain patient. Brain, 138(3), 604-615.
[2] Sari et al. (2022). Multimodal investigation of neuroinflammation in aviremic patients with HIV on antiretroviral therapy and HIV elite controllers. Neurology Neuroimmunology Neuroinflammation, 9(2), e1144.