Poster No:
2041
Submission Type:
Abstract Submission
Authors:
Randy Hirschtick1, Sarasa Tohyama2, Michael Datko2, Ludovica Brusaferri3, Lillian Kinder3, Jack Schnieders3, Mackenzie Hyman3, Alison Goldstein2, Melaina Gilbert2, Hope Housman2, Vi Le3, Frances Marin4, Megan Heffernan3, Kassandra Round2, Ronald Garcia3, Robert Edwards5, Bruce Rosen3, Nouchine Hadjikhani3, Hsinlin Cheng6, Zev Schuman-Olivier7, Marco Loggia3, Vitaly Napadow2
Institutions:
1Dept. Psychiatry & Martinos Center, MGH, Harvard Med School, Boston, MA, 2Dept Physical Medicine & Rehabilitation, Spaulding Rehabilitation Hospital, Harvard Medical School, Boston, MA, 3Martinos Center, Dept Radiology, MGH, Harvard Med School, Boston, MA, 4Center for Mindfulness and Compassion, Dept of Psychiatry, Cambridge Health Alliance, HMS, Cambridge, MA, 5Dept of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women’s Hospital, HMS, Boston, MA, 6Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 7Center for Mindfulness and Compassion, Cambridge Health Alliance, Cambridge, MA
First Author:
Co-Author(s):
Sarasa Tohyama
Dept Physical Medicine & Rehabilitation, Spaulding Rehabilitation Hospital, Harvard Medical School
Boston, MA
Michael Datko
Dept Physical Medicine & Rehabilitation, Spaulding Rehabilitation Hospital, Harvard Medical School
Boston, MA
Lillian Kinder
Martinos Center, Dept Radiology, MGH, Harvard Med School
Boston, MA
Jack Schnieders
Martinos Center, Dept Radiology, MGH, Harvard Med School
Boston, MA
Mackenzie Hyman
Martinos Center, Dept Radiology, MGH, Harvard Med School
Boston, MA
Alison Goldstein
Dept Physical Medicine & Rehabilitation, Spaulding Rehabilitation Hospital, Harvard Medical School
Boston, MA
Melaina Gilbert
Dept Physical Medicine & Rehabilitation, Spaulding Rehabilitation Hospital, Harvard Medical School
Boston, MA
Hope Housman
Dept Physical Medicine & Rehabilitation, Spaulding Rehabilitation Hospital, Harvard Medical School
Boston, MA
Vi Le
Martinos Center, Dept Radiology, MGH, Harvard Med School
Boston, MA
Frances Marin
Center for Mindfulness and Compassion, Dept of Psychiatry, Cambridge Health Alliance, HMS
Cambridge, MA
Megan Heffernan
Martinos Center, Dept Radiology, MGH, Harvard Med School
Boston, MA
Kassandra Round
Dept Physical Medicine & Rehabilitation, Spaulding Rehabilitation Hospital, Harvard Medical School
Boston, MA
Ronald Garcia
Martinos Center, Dept Radiology, MGH, Harvard Med School
Boston, MA
Robert Edwards
Dept of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women’s Hospital, HMS
Boston, MA
Bruce Rosen
Martinos Center, Dept Radiology, MGH, Harvard Med School
Boston, MA
Hsinlin Cheng
Department of Neurology, Massachusetts General Hospital, Harvard Medical School
Boston, MA
Zev Schuman-Olivier
Center for Mindfulness and Compassion, Cambridge Health Alliance
Cambridge, MA
Marco Loggia
Martinos Center, Dept Radiology, MGH, Harvard Med School
Boston, MA
Vitaly Napadow
Dept Physical Medicine & Rehabilitation, Spaulding Rehabilitation Hospital, Harvard Medical School
Boston, MA
Introduction:
Migraine, a highly prevalent and disabling neurological condition, involves sensitization of the trigeminal system (Charles, 2018; Noseda and Burstein, 2013) and patients with this condition often report sensory hypersensitivities such as allodynia and hyperalgesia (Minguez-Olaondo et al. 2022; Toriyama et al. 2017). Our study using [11C]PBR28 PET/MRI in combination with ultra-high field (7T) MRI to investigate the function-structure associations of the trigeminal system in participants with migraine disorder enabled us to examine the association between this functional response, white matter structural integrity of the trigeminal nerve, and a PET imaging marker of neuroinflammatory marker 18kDa translocator protein (TSPO) (Albrecht, 2019).
Methods:
We enrolled 60 patients and 20 healthy controls who completed electronic daily headache diaries for at least one month (patients: 4-15 headache days/month, 55F, mean age±SD: 36.28±11.95 years; controls 19F, 35.45±13.30 years). All participants underwent a 7T MRI session to acquire an fMRI scan (SMS acceleration factor = 4, TR = 1.19s, TE = 22ms, resolution = 1.5mm isotropic) and DTI scan (64 directions, b=1,000, TR = 5.9s, TE = 68ms, resolution = 1mm isotropic) and a PET scan if they were either high-affinity (N=20) or mixed-affinity (N=20) binders (HABs/MABs), based on their polymorphism in the TSPO gene. [11C]PBR28 PET scanning was performed with a 3T Tim Trio whole-body MRI with a dedicated brain PET insert (Kolb, 2012). Innocuous electrical forehead stimulation was applied to investigate brainstem fMRI response to trigeminal sensory afference. Stimulation was delivered at 5 Hz with amplitude 7 mA, unless rated as imperceptible or above pain threshold before fMRI (0-10: no sensation-pain detection threshold), and applied using a block fMRI design (ON: 8s, OFF: 14s). Daily diaries prior to the MRI session provided the number of headache days and headache pain intensity (0-10: no pain-worst possible pain).
A group-averaged general linear model (GLM) yielded a fMRI activation map for both whole-brain and brainstem response to trigeminal sensory stimulation. To explore function-structure associations, fractional anisotropy (FA) from the root entry zone of both trigeminal nerves was added as covariate to the fMRI GLM. All group-level analyses were carried out using FMRIB's Local Analysis of Mixed Effects (FSL, FLAME 1+2) for the whole-brain (Z > 2.3, p < 0.05) and brainstem (thresholded at uncorrected p < 0.05), respectively. SUV ratio (SUVR) images were obtained from the PET scans and intensity normalized using the cerebellum as a pseudo-reference region (Lyoo, 2015). FA was compared between patients and controls. FA was also correlated with the PET signal and brainstem fMRI response in the migraine cohort. Associations between imaging and headache characteristics were also explored.
Results:
Migraine patients demonstrated altered white matter microstructure at the trigeminal nerve root (n=53), including reduced FA, compared to controls (n=18). In patients, lower FA was accompanied by elevated [11C]-PBR28 PET signal at the nerve root (n=36) and lower fMRI activation in an ipsilateral pontine cluster consistent with spinal trigeminal nucleus (n=51). These findings were more robust on the right side, consistent with the observation that right headache dominant patients demonstrated higher migraine severity compared to left headache dominant patients in our cohort.
Conclusions:
Migraine patients demonstrate altered trigeminal nerve white matter microstructure and SpV fMRI response to trigeminal sensory afference. Furthermore, the greater the microstructural alteration of the nerve, the greater the neuroinflammation in the same anatomical region and less functional communication present in its associated brainstem nuclei. Trigeminal system remodeling may be an important aspect of the dynamics underlying migraine pathophysiology.
Modeling and Analysis Methods:
Diffusion MRI Modeling and Analysis
Novel Imaging Acquisition Methods:
Diffusion MRI
Multi-Modal Imaging 2
PET
Perception, Attention and Motor Behavior:
Perception: Pain and Visceral 1
Keywords:
Brainstem
FUNCTIONAL MRI
HIGH FIELD MR
Pain
Positron Emission Tomography (PET)
Tractography
Other - Migraine
1|2Indicates the priority used for review
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Please indicate below if your study was a "resting state" or "task-activation” study.
Resting state
Task-activation
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Healthy subjects only or patients (note that patient studies may also involve healthy subjects):
Patients
Was this research conducted in the United States?
Yes
Are you Internal Review Board (IRB) certified?
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Were any human subjects research approved by the relevant Institutional Review Board or ethics panel?
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Yes
Were any animal research approved by the relevant IACUC or other animal research panel?
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Not applicable
Please indicate which methods were used in your research:
PET
Functional MRI
Structural MRI
Diffusion MRI
For human MRI, what field strength scanner do you use?
7T
Which processing packages did you use for your study?
SPM
FSL
Provide references using APA citation style.
Charles A. (2018) The pathophysiology of migraine: implications for clinical management. Lancet Neurol., 17(2):174-182.
Noseda R, Burstein R. (2013) Migraine pathophysiology: anatomy of the trigeminovascular pathway and associated neurological symptoms, CSD, sensitization and modulation of pain. Pain, 154 Suppl 1:S44-53.
Minguez-Olaondo A, et al. (2022) Cutaneous Allodynia in Migraine: A Narrative Review. Front Neurol., 12:831035.
Toriyama T, Horiuchi T, Hongo K. (2017) Characterization of migraineurs presenting interictal widespread pressure hyperalgesia identified using a tender point count: a cross-sectional study. J Headache Pain, 18(1):117.
Albrecht DS, Mainero C, Ichijo E, et al. (2019) Imaging of neuroinflammation in migraine with aura: A [11C]PBR28 PET/MRI study. Neurology, 92(17):e2038–50.
Kolb A, et al. (2012) Technical performance evaluation of a human brain PET/MRI system. Eur Radiol, 22(8):1776–88.
Lyoo CH, et al. (2015) Cerebellum Can Serve As a Pseudo-Reference Region in Alzheimer Disease to Detect Neuroinflammation Measured with PET Radioligand Binding to Translocator Protein. J Nucl Med Off Publ Soc Nucl Med., 56(5):701–6.
No