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Thao T. Tran, BSc, ARMRIT Director of Clinical Services/Senior MR Tech Advanced Imaging & Spectroscopy Center Huntington Medical Research Institutes 10 Pico Street, Pasadena, CA 91105 Orest B. Boyko MD PhD University of Southern California Keck School of Medicine 1500 San Pablo Avenue Los Angeles CA 90033 Disclosure O Boyko- Speakers Bureau Bracco Diagnostics, Guerbet LLC T Tran- No Disclosures PURPOSE Our initial study utilizes magnetic resonance spectroscopy to evaluate possible changes of MRS biomarkers Choline, Myo-inositol, and N-acetyl aspartate changes in the dentate nuclei region of patients who have had multiple Gd contrast injections and demonstrated T1 hyperintensity in the Dentate Nuclei. MATERIALS AND METHODS Two subjects (1 brain tumor and 1 multiple sclerosis) with histories of multiple gadolinium-based contrast injections and four patients with no history of gadoliniumbased contrast injections underwent magnetic resonance (MR) examinations on a General Electric 1.5T clinical scanner in the region of the dentate nucleus using single voxel point resolved spectroscopy (PRESS) TE 35 msec TR 1500 msec (Fig. 1). RESULTS Fig 1 RESULTS The two subjects with history of multiple gadolinium-based contrast administrations demonstrate (Fig. 2A,B) : 1. Increase in mI/Cr compared to normal controls (p < 0.05) 2.Cho/Cr also was elevated but minimally. Bright Dentate Nucleus Subjects Red Square and Green Tirangle Normal control atients no Bright Dentate Nucleus Blue Diamond NeuroMetabolites of MRS and Their Histologic Correlates MRS NeuroMetabolites- A Primer A. 2.0 ppm - N acetyl aspartate 2.0 ppm (NAA): Is an aminoacid derivative synthesized in neurons and transported along axons. It is therefore a "marker" of viable neurons, axons, and dendrites B. 2.1 and 2.4 ppm - Glutamate—Glutamine—Gammaamino butyrate (Glx): A mixture of closely related amino acids, amines and derivatives involved in excitatory neurotransmission Glx is a vital marker(s) in MRS of stroke, lymphoma, hypoxia, and many metabolic brain disorders. glutamine is mainly synthesized in the glia from synaptic glutamate and has been used as an index of glutamatergic neurotransmission. GABA is the principal inhibitory neurotransmitter in the CNS C. 3.0 ppm - Creatine (Cr): It is the central energy marker of both neurons and astrocytes and remains relatively constant MRS NeuroMetabolites- A Primer A. 3.2 ppm - Choline (Cho): Choline includes several soluble components of brain myelin and fluid-cell membranes. Because by far the majority of cholinecontaining brain constituents are not normally soluble, pathological alterations in membrane turnover (tumor, leukodystrophy, multiple sclerosis) result in a massive increase in MRS-visible Cho. B. 3.6 ppm - Myo-inositol (mI): A little known polyol (sugar-like molecules) and as an astrocyte marker and osmolyte, mI contributes specificity in dementia diagnoses1, inflammation, low grade gliomas and an almost absolute specificity to hepatic encephalopathy and hyponatremic brain syndromes. Myoinositol is a precursor in the phosphatidylinositol second messenger system, and is also a glial marker. CONCLUSIONS Currently, there are no noninvasive methods to evaluate metabolic changes in the brains of patient who exhibit T1 hyperintense signal in the dentate nucleus after multiple gadolinium injections. Magnetic resonance spectroscopy has been shown to be a reliable and reproducible method of assessing chemical changes in the brain and potentially can be established as a monitoring tool for metabolic changes in patients receiving medical necessary multiple gadolinium injections. REFERENCES 1. Kanda T, Ishii, K, Kawaguchi H, et al. High Signal Intensity in the Dentate Nucleus and Globus Pallidus on Unenhanced T1-weighted MR Images: Relationship with Increasing Cumulative Dose of a Gadolinium-based Contrast Material. Radiology 2014; 270(3):834-841. 2. Huang DQ, Prince M, Shih G, Cao Y. Signal changes in dentate nuclei with 10 or more gadolinium-based contrast administrations: comparison of linear versus macrocytic contrast agents. Proc ISMRM 2015: EPS07ABSTRACT 3229 3. De Stefano N, Dotti MT, Mortilla M, Federico A. Magnetic resonance imaging and spectroscopic changes in brains of patients with cerebrotendinous xanthomatosis. Brain 2001; 121:121-131. 4. Wallis LI, Griffiths PD, Ritchie SJ, Romanowski CA, Darwent G, Wilkinson ID. Proton spectroscopy and imaging at 3T in ataxia-telangiectasia. AJNR 2007; 28:79-83. 5. Rogosnitzky M, Branch S. Gadolinium-based contrast agent toxicity: a review of known and proposed mechanisms. BioMetals 2016; online April 6 2016 <link.springer.com/article/10.1007/s10534-106-9931-7>