INTERESTING IMAGE Simultaneous 18F-FDG PET/MRI Assists Diagnosis of a Rare Disease, MELAS Fang Liu, MD, Weiwei Ruan, PhD, Yichun Wang, BS, and Xiaoli Lan, MD, PhD Abstract: MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes) is a rare congenital mitochondrial DNA mutation disease. Here, we report a 4-year-old girl, who presented with short stature, mental retardation, and recurrent seizures, underwent simultaneous 18F-FDG PET/ MRI examination. An interesting contradiction images were found on bilateral frontal, left temporal, occipital, and parietal lobes, which were with high blood flow shown on 3D-ASL perfusion images, but low uptake of 18F-FDG on PET images. The contradiction of high blood flow and low glucose metabolism gave us a clue to make the diagnosis of MELAS. The final diagnosis was MELAS confirmed by genetic testing. Key Words: PET/MR, 18F-FDG, MELAS, diagnosis, simultaneous (Clin Nucl Med 2019;44: 81–82) Received for publication August 14, 2018; revision accepted September 17, 2018. From the *Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology; and †Hubei Key Laboratory of Molecular Imaging, Wuhan, China. Conflicts of interest and sources of funding: This work was supported by the Key Project of Hubei Province Technical Innovation Special Funding (no. 2017ACA182), and the Clinical Research Physician Program of Tongji Medical College, Huazhong University of Science and Technology (no. 5001530008). None declared to all authors. Correspondence to: Xiaoli Lan, MD, PhD, Department of Nuclear Medicine, Union Hospital Tongji Medical College, Huazhong University of Science and Technology, No. 1277 Jiefang Ave, Wuhan 430022, China. E-mail: LXL730724@hotmail.com. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved. ISSN: 0363-9762/19/4401–0081 DOI: 10.1097/RLU.0000000000002344 REFERENCES 1. Bannwarth S, Procaccio V, Lebre AS, et al. Prevalence of rare mitochondrial DNA mutations in mitochondrial disorders. J Med Genet. 2013;50:704–714. 2. Shelly MJ, Kelly P, O'Connell MJ. FDG-PET imaging in the investigation of homonymous hemianopia in a patient with MELAS syndrome. Clin Nucl Med. 2007;32:479–480. 3. El-Hattab AW, Adesina AM, Jones J, et al. MELAS syndrome: Clinical manifestations, pathogenesis, and treatment options. Mol Genet Metab. 2015;116:4–12. 4. Yoshii Y, Yoneda M, Ikawa M, et al. Radiolabeled Cu-ATSM as a novel indicator of overreduced intracellular state due to mitochondrial dysfunction: studies with mitochondrial DNA-less ρ0 cells and cybrids carrying MELAS mitochondrial DNA mutation. Nucl Med Biol. 2012;39:177–185. 5. Ikawa M, Okazawa H, Arakawa K, et al. PET imaging of redox and energy states in stroke-like episodes of MELAS. Mitochondrion. 2009;9:144–148. 6. Ikawa M, Yoneda M, Muramatsu T, et al. Detection of preclinically latent hyperperfusion due to stroke-like episodes by arterial spin-labeling perfusion MRI in MELAS patients. Mitochondrion. 2013;13:676–680. 7. Yoneda M, Ikawa M, Arakawa K, et al. In vivo functional brain imaging and a therapeutic trial of L-arginine in MELAS patients. Biochim Biophys Acta. 2012;1820:615–618. 8. Haast RAM, Ivanov D, IJsselstein RJT, et al. Anatomic & metabolic brain markers of the m.3243A>G mutation: A multi-parametric 7T MRI study. Neuroimage Clin. 2018;18:231–244. Clinical Nuclear Medicine • Volume 44, Number 1, January 2019 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved. www.nuclearmed.com 81 Liu et al Clinical Nuclear Medicine • Volume 44, Number 1, January 2019 FIGURE 1. MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes) is a rare congenital mitochondrial DNA mutation disease. A 4-year-old girl, who presented with short stature, mental retardation, and recurrent seizures, underwent 18 F-FDG PET/MRI examination. A–G, Images from left to right, represent the same level images from base to top of the skull. Diffused atrophy with widening susci was shown on T1- (A) and T2-weighted images (B). Hyperintensity was found in bilateral frontal, left temporal, occipital, and parietal lobes on T2 flair images (C). DWI showed diffusion restricted in the left temporoparietal lobe (D). 3D-ASL perfusion images showed increased cerebral blood flow in the regions consistent with the hyperintensity on T2-flair images (E). However, low 18F-FDG uptake was noticed in bilateral frontal lobe, left temporal, occipital, and parietal cortex on PET images (F) and PET-T2 flair fused images (G), which was contradicted with the hyperperfusion shown on 3D-ASL perfusion images (E). The contradiction of high blood flow and low glucose metabolism gave us a clue to make the diagnosis of MELAS. The final diagnosis was MELAS, which was confirmed by genetic testing with the result of A to G translation at nucleotide 3243 of mitochondrial DNA. MELAS is a rare maternal inheritant diseases mainly caused by m.3243A>G mutation within the mitochondrial DNA (mtDNA)–encoded tRNA leucine 1 (MTTL1) gene.1 This patient was detected m.3243A>G mutation 100% loaded in urine and cerebral spinal fluid, and 72.7% loaded in blood. MELAS has multisystem symptoms with onset typically in childhood. The common triad symptoms are lactic acidosis, seizures, and stroke-like episodes, other symptoms include short stature, sensorineural hearing loss, diabetes, cardiomyopathy, and dementia.2,3 The point mutation in mtDNA induces the metabolic disorders at cellular level, which leads to generate reactive oxygen species, increase oxidative stress, and damage surrounding cells.4,5 Furthermore, it leads to endothelial dysfunction of cerebral blood vessels, which corresponds with cerebral hyperperfusion, vasodilatation, and vasogenic edema in acute lesions. In contrast, the glucose metabolism decreases due to the impaired mitochondrial and respiratory dysfunction.6,7 Simultaneous PET/MRI is an important imaging modality to display the abnormalities of MELAS. 18F-FDG PET shows the glucose metabolism decreased on the lesion, and MRI provides diagnostic information of fine-scale structural and functional properties and changes in the brain.8 Thus, hybrid PET/MRI contributes to a better understanding of the disease pathology. 82 www.nuclearmed.com © 2018 Wolters Kluwer Health, Inc. All rights reserved. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.