Traumatic brain injury (TBI) is the world's leading cause of neurological disability in the young adult and middle-aged population. The role of computed tomography (CT) and magnetic resonance imaging (MRI) in patient management is limited due to the widespread presence of clinically-relevant, but imaging-occult injury. We propose new metrics of TBI damage obtained from sodium (23Na) MRI and proton MR spectroscopy (1H MRS). The central hypothesis is that conjoint 23Na MRI/1H MRS will provide metabolic imaging markers for loss of ion homeostasis and neurodegeneration, which will predict patients? long-term clinical outcome. Sodium MRI is a non-invasive modality based on the direct detection of Na+ ions using dedicated MRI software and hardware. It can assess loss of Na+ homeostasis, which can be disturbed by processes where ionic imbalance is the driving force behind the cascade of cell damage. The Na+/K+ exchange pump can be affected by energy deficits due to mitochondrial dysfunction, as well as by diffuse axonal injury, the histopathological signature of TBI. This would result in variations of the intracellular sodium concentration (C1), while inflammation, gliosis and cell loss would be reflected in variations of the extracellular volume fraction (alpha2). We propose to combine the 23Na metrics C1 and alpha2 with 1H MRS, from which quantification of N-acetylaspartate (NAA), creatine (Cr), choline (Cho) and myo-inositol (mI) can be used to infer neuronal health/density (NAA), cellular energy/density (Cr), membrane turnover (Cho) and astrocytic activation (mI).
Specific aims are:
AIM 1 : Methodology. (1.a) To optimize ultrashort echo-time 23Na MRI with and without fluid suppression at 3 T. To optimize image reconstruction with denoising and compressed sensing to increase signal-to-noise ratio, resolution and speed of acquisition. To develop C1 and alpha2 quantification based on 23Na spin dynamics simulation and reference phantoms. (1.b) To implement whole-brain 1H MRS acquisition with 4th order shimming.
AIM 2 : Clinical application. (2.a) To compare C1 and alpha2 in TBI patients and controls at baseline (?10 days after TBI) and their rates of change over time (2- month and 1-year follow-ups for TBI, 1-year follow-up for controls), adjusted for MRI (FLAIR, SWI, DTI) and 1H MRS. (2.b) To correlate the baseline values of the MR metrics, and their rates of change over time, with clinical outcome at the two follow-ups. To assess the added value of C1 and alpha2 to MRI and 1H MRS.
AIM 3 : Mechanistic model. (3.a) Given the interdependence between ATP and both NAA and C1, to determine whether TBI-related changes in C1 are glial or neuronal. (3.b) To test whether, based on a mechanistic model of neurodegeneration: (i) baseline 23Na MRI and 1H MRS findings will be moderated by injury severity; (ii) longitudinal 23Na MRI and 1H MRS changes consistent with neurodegeneration will correlate with worse clinical outcome at the two follow-ups. (3.c) To determine which MR measurements (or combinations thereof) are best predictors of long-term TBI outcome, based on the mechanistic model and the longitudinal data.
Every year over two million people suffer traumatic brain injury (TBI), which can lead to permanent neurological deficits, the biological correlates of which are often missed by conventional imaging. We propose the use of sodium MRI and proton MR spectroscopy to study a class of metabolic injury, previously not investigated in TBI. The central premise is that the use of both techniques will inform about TBI pathogenesis and provide new imaging markers for the injury underlying patients? disabilities and symptoms.
|Nunes Neto, Lucidio P; Madelin, Guillaume; Sood, Terlika Pandit et al. (2018) Quantitative sodium imaging and gliomas: a feasibility study. Neuroradiology 60:795-802|
|Khegai, Oleksandr; Madelin, Guillaume; Brown, Ryan et al. (2018) Dynamic phosphocreatine imaging with unlocalized pH assessment of the human lower leg muscle following exercise at 3T. Magn Reson Med 79:974-980|
|Madelin, Guillaume; Xia, Ding; Brown, Ryan et al. (2018) Longitudinal study of sodium MRI of articular cartilage in patients with knee osteoarthritis: initial experience with 16-month follow-up. Eur Radiol 28:133-142|
|Lakshmanan, Karthik; Brown, Ryan; Madelin, Guillaume et al. (2018) An eight-channel sodium/proton coil for brain MRI at 3 T. NMR Biomed 31:|
|Hoch, Sarah E; Kirov, Ivan I; Tal, Assaf (2017) When are metabolic ratios superior to absolute quantification? A statistical analysis. NMR Biomed 30:|
|Kirov, Ivan I; Liu, Shu; Tal, Assaf et al. (2017) Proton MR spectroscopy of lesion evolution in multiple sclerosis: Steady-state metabolism and its relationship to conventional imaging. Hum Brain Mapp 38:4047-4063|
|Davitz, Matthew S; Wu, William E; Soher, Brian J et al. (2017) Quantifying global-brain metabolite level changes with whole-head proton MR spectroscopy at 3T. Magn Reson Imaging 35:15-19|
|Gilles, Alina; Nagel, Armin M; Madelin, Guillaume (2017) Multipulse sodium magnetic resonance imaging for multicompartment quantification: Proof-of-concept. Sci Rep 7:17435|
|Shepherd, Timothy M; Kirov, Ivan I; Charlson, Erik et al. (2017) New rapid, accurate T2 quantification detects pathology in normal-appearing brain regions of relapsing-remitting MS patients. Neuroimage Clin 14:363-370|
|Kirov, Ivan I; Wu, William E; Soher, Brian J et al. (2017) Global brain metabolic quantification with whole-head proton MRS at 3 T. NMR Biomed 30:|
Showing the most recent 10 out of 11 publications