{'fraction_non_alphanumeric': 0.028754700287547, 'fraction_numerical': 0.018026985180269853, 'mean_word_length': 4.8988910632746245, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Extremely low 18F-fluorodeoxyglucose uptake in the brain of a patient with metastatic neuroblastoma and its recovery after chemotherapy: A case report

Commonly, physiological 18F-fluorodeoxyglucose (FDG) uptake in the brain can be observed in 18F-FDG positron emission tomography. Abnormal uptake of 18F-FDG in the brain suggests disorders of central nervous system. Here, we present a case of extremely low 18F-FDG uptake in the brain of a 4-year-old girl with whole-body metastatic neuroblastoma. Almost missing of physiological 18F-FDG uptake in the brain was ascribed at least partly to the metastatic neuroblastoma. The brain could regain physiological 18F-FDG uptake after chemotherapy.


18
F-fluorodeoxyglucose (FDG) positron emission tomography (PET) is one of functional imaging techniques. 18 Ffluorodeoxyglucose, an analog of glucose, accumulates in tissue with high glucose metabolism. 18 F-fluorodeoxyglucose positron emission tomography is useful to find metastasis of malignant tumors on the whole body. In the living body, some organs, for example, the brain, show physiological uptake of 18 F-FDG. Abnormally low 18 F-FDG uptake in the brain suggests disorders of central nervous system (CNS). Here, we present a case of extremely low 18 F-FDG uptake in the brain of a 4-year-old girl with whole-body metastatic neuroblastoma.

Case report
A 4-year-old girl presented with a 2-week history of malaise, appetite loss, and pain in both legs. She looked pale with eyelid edema. She had no abnormalities in birth or development. There was no significant family history. Laboratory test showed anemia, thrombocytopenia, high neuron-specific enolase (NSE) level, and increased urinary catecholamine metabolites. Bone marrow aspiration revealed infiltration of tumor cells. Computed tomography (CT) showed a 70-mm right adrenal tumor and some satellite lesions. 18 F-fluorodeoxyglucose positron emission tomography/ computed tomography (Philips Vereos digital scanner 1 with high spatial resolution by a semiconductor detector) was performed, providing some interesting images ( Figure 1). A maximum intensity projection (MIP) image showed an impactful appearance like a skeleton. Strong uptake was seen in the bone marrow (SUVmax 7.6 at sacrum) and in the liver (SUVmax 10.0). However, the right adrenal tumor had only a slight accumulation on the margin. A surprising finding is almost missing of physiological 18 F-FDG uptake in the brain ( Figure 2, SUVmax 1.8), mimicking brain death. 2 She did not present with disturbance of consciousness nor neurological signs during the procedure. Magnetic resonance imaging (MRI) revealed no abnormal findings in the brain ( Figure 2). 123 I-metaiodobenzylguanidine (MIBG) scintigraphy showed unclear uptake of the adrenal tumor but remarkable uptake in the bone marrow and in the liver ( Figure 1). Final diagnosis by a biopsy of the right adrenal lesion was neuroblastoma.
We initiated induction chemotherapy. 3 The next day she developed multiple organ failure due to tumor lysis-related bleeding from the liver. After she had been cared for 1 month in an intensive care unit, she resumed chemotherapy. Some laboratory tests and image inspections ( Figure 3) were done to confirm the therapeutic effect. Significant reductions in serum NSE and urinary catecholamine metabolites were revealed. 18 F-fluorodeoxyglucose positron emission tomography/computed tomography (Siemens Biograph 64 TruePoint scanner) demonstrated the disappearance of most of the metastasis. The brain regained its physiological uptake of 18 F-FDG (SUVmax 9.5). 123 Imetaiodobenzylguanidine scintigraphy and bone marrow biopsy also confirmed complete remission of the disease.

18
F-fluorodeoxyglucose positron emission tomography is one of the functional imaging techniques. 18 F-fluorodeoxyglucose, an analog of glucose, is taken up into cells by glucose transporters. 4 Subsequently, 18 F-FDG is converted to 18 F-FDG-6-phosphate by the enzyme hexokinase and is trapped inside cells. 18 F-fluorodeoxyglucose positron emission tomography can be used to assess regional glucose metabolism in the human body. Major usage of 18 F-FDG PET is to find metastasis of malignant tumors on the whole body.
When it comes to neuroblastoma, 123 I-MIBG scintigraphy is generally used as a disease-specific imaging modality. In addition, 18 F-FDG PET is combined to it because better sensitivity and specificity are achieved. 5 In this case, the accumulation of 123 I-MIBG to the right adrenal tumor was unclear due to most necrosis inside the tumor. However, 18 F-FDG PET with high spatial resolution revealed slight accumulation on the margin of the tumor and wholebody metastasis including a tiny lesion on the cranium.    Physiological accumulation of 18 F-FDG in some organs is one of the pitfalls when interpreting acquired images of 18 F-FDG PET. 6 For example, the liver or the heart shows high uptake of 18 F-FDG, which reflects its physiologically high glucose metabolism. The urinary tract (renal pelvis, ureter, and urinary bladder) exhibits high accumulation because of excretion of 18 F-FDG into urine. The brain also highly metabolizes glucose due to almost limited energy source to glucose for neuron and glial cells.
Deviation from physiological uptake pattern of 18 F-FDG suggests some abnormality. 18 F-fluorodeoxyglucose positron emission tomography imaging of the brain is used for assessment of CNS disorders with glucose metabolic changes related to neuronal and synaptic activity. Brain death is indicated by absence of 18 F-FDG uptake in the brain. 2 Neurodegeneration diseases, such as Alzheimer's disease or other dementias, present specific hypometabolic patterns. 7 Central nervous system tumors show hypo-or hypermetabolism depending on the malignancy of the tumor in the localized lesions. 8 Infectious or autoimmune encephalitis demonstrates abnormal glucose metabolism reflecting brain inflammation. 9,10 In epilepsy, a scan is performed in the seizure-free interval and can detect low metabolic area corresponding to the focus of epilepsy. 11 In other literature, anomalies of 18 F-FDG uptake in the brain were reported in some neurological or psychiatric disorder. 12,13 Here, we experienced a case of extremely low 18 F-FDG uptake in the brain of a 4-year-old girl with whole-body metastatic neuroblastoma. Almost missing of physiological uptake of 18 F-FDG first suggested an error of pre-inspection conditions about blood glucose level. 14 She had no history of diabetes. The fasting time before 18 F-FDG injection was 20 h and no uptake elevation in the skeletal muscle was observed. Next, some CNS disorder was suspected. However, she was clearly conscious and exhibited no neurological signs during the procedure. MRI did not reveal brain atrophy or other anomalies except small metastasis on the cranium. CNS metastasis was not recognized at diagnosis and possibility of CNS relapse during the course was thought to be low because lumbar puncture, one of risk factors, was not done although MYCN amplification, another risk factor, was not inspected.
Injected dosage of 18 F-FDG was about 4.5 MBq/kg. A loss of dosage is negligible when a small lesion exists. However, a larger volume of the lesion possibly effects the distribution. For example, running promoted glucose metabolism in the large skeletal muscle of the lower extremities. Increased accumulation of 18 F-FDG in the skeletal muscle was balanced by reduction of uptake in the abdominal organs. 15 However, brain uptake did not show statistically significant change because biological homeostasis regulated blood flow and preserved brain function. In recent studies for malignancy, metabolic tumor volume or total lesion glycolysis (TLG) was used to evaluate malignant tumors. [16][17][18] Total lesion glycolysis is a product of mean SUV and tumor volume. A study reported that TLG was negatively correlated with a 18 F-FDG uptake in the brain. 19 Higher TLG means that a significant part of injected 18 F-FDG is caught to tumor and a less portion of the tracer is distributed to whole-body organs.
Regarding this case, an outstanding picture of 18 F-FDG PET/CT MIP reflected large volume of metastatic neuroblastoma and strong accumulation of 18 F-FDG with high SUV value. Pathologically, the worse condition of the disease was confirmed because of poorly differentiated subtype and high mitosis-karyorrhexis index in a pathological diagnosis 20 and high-risk group as International Neuroblastoma Risk Group. 21 A large amount of tumor with high SUV value was thought to affect extremely low uptake of 18 F-FDG in the brain. Regaining physiological uptake after chemotherapy could prove the normal CNS and support this idea.
In conclusion, we present a rare case of extremely low uptake of 18 F-FDG in the brain. We thought that this phenomenon was ascribed at least partly to the elevated metabolism in the metastatic neuroblastoma. Our finding can provide an idea to avoid one of the pitfalls in oncological imaging.