Prognostic Value of SSTR-derived Volumetric Parameters from a Hybrid Standardized Uptake Value Thresholding Method in Patients with 68Ga-DOTATATE-avid Stage IV Neuroendocrine Neoplasms: A preliminary study.

INTRODUCTION: The ability of PET/CT imaging to delineate neuroendocrine neoplasms (NENs) and predict prognosis in affected patients is often compromised by substantial uptake heterogeneity. We hereby proposed a hybrid standardized uptake value (SUV) thresholding algorithm to extract volumetric parameters from somatostatin receptor (SSTR) PET/CT imaging, and investigate their prognostic performance in patients with 68Ga-DOTATATE-avid stage IV NENs. METHODS: For 38 retrospectively enrolled patients, we used either fixed SUV thresholding of normal liver parenchyma (method A), 41% of the SUVmax for each lesion (method B), or a hybrid method (method A for liver metastases; fixed SUV threshold of normal bone for bone metastases; method B for primary tumors and other metastases) to quantify the whole-body SSTR-expressing tumor volume (SRETVwb) and total lesion SSTR expression (TLSREwb). Patient survival was also recorded and analyzed. RESULTS: PET/CT images revealed heterogeneous uptake of 68Ga-DOTATATE at primary and metastatic sites. Progression-free (PFS) and overall survival (OS) were negatively correlated with the extent of liver or bone metastases (P < 0.05), but not significantly correlated with tumor grade or 18F-FDG PET/CT positivity. By the hybrid method, PFS was significantly shorter in patients with high SRETVwb, and OS was significantly shorter in those with high SRETVwb and TLSREwb (P < 0.05). However, when derived from method A or method B, neither SRETVwb nor TLSREwb could predict patient outcomes. CONCLUSION: Compared with other methods used in 68Ga-DOTATATE-avid stage IV NENs, our hybrid SUV thresholding method demonstrated robustness, with greater precision, reliability, and prognostic power.

Lateralization of the crossed cerebellar diaschisis-associated metabolic connectivities in cortico-ponto-cerebellar and cortico-rubral pathways.

This study aimed to explore the glucose metabolic profile of extrapyramidal system in patients with crossed cerebellar diaschisis (CCD). Furthermore, the metabolic connectivities in cortico-ponto-cerebellar and cortico-rubral pathways associated with CCD were also investigated. A total of 130 CCD positive (CCD+) and 424 CCD negative (CCD-) patients with unilateral cerebral hemisphere hypometabolism on 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) were enrolled. Besides, the control group consisted of 56 subjects without any brain structural and metabolic abnormalities. Apart from the "autocorrelation", metabolic connectivity pattern of right or left affected cerebellar hemisphere involved unilateral (left or right, respectively) caudate, pallidum, putamen, thalamus and red nucleus, in CCD+ patients with left or right supratentorial lesions, respectively (Puncorrected < 0.001, cluster size > 200). CCD+ group had significantly lower asymmetry index (AI) in cortico-ponto-cerebellar pathway (including ipsilateral cerebral white matter, ipsilateral pons, contralateral cerebellum white matter and contralateral cerebellum exterior cortex) and cortico-rubral pathway (including ipsilateral caudate, thalamus proper, pallidum, putamen, ventral diencephalon and red nucleus) than those of both CCD- and control groups (all P < 0.05). AI in contralateral cerebellum exterior cortex was significantly positively correlated with that in ipsilateral caudate, putamen, pallidum, thalamus proper, ventral diencephalon, red nucleus and pons among CCD+ group (all P < 0.01), but only with that in ipsilateral caudate and putamen among CCD- group (both P < 0.001). These results provide additional insight into the involvement of both cortico-ponto-cerebellar and cortico-rubral pathways in the presence of CCD, underlining the need for further investigation about the role of their aberrant metabolic connectivities in the associated symptoms of CCD.

Towards characterizing the regional cerebral perfusion in evaluating the severity of major depression disorder with SPECT/CT.

BACKGROUND: Major depressive disorder (MDD) is a common mental disorder worldwide, but now there is a lack of clinically effective assessment and management of MDD. In this study, we used technetium-99 m ethylcysteinate dimer ([99mTc]ECD) SPECT/CT to characterize the regional cerebral blood flow (rCBF) status of MDD patients, and to explore an objective image assessment model of MDD which is non- or minimally-invasive, convenient and accurate in a clinical setting. METHODS: The severity of MDD was assessed by three trained psychiatrists, based on scores obtained from HAMD and HAMA. [99mTc]ECD rCBF SPECT/CT was performed in 20 healthy controls and 74 unipolar MDD patients before receiving the treatment. The CT attenuation-corrected SPECT images data were automatically registered, analyzed simultaneously by 3D-SSP and eZIS. RESULTS: The mean score of HAMD and HAMA in the MDD patients was 25.49 ± 6.00, and 23.12 ± 5.83, respectively. There was a positive correlation between two scores. The MDD women had higher HAMD scores than MDD men. The decreased rCBF of MDD patients in frontal lobes (bilateral B11, B47 and right B4, B6, B10, B46), temporal lobe (right B21, B41, B42) and cingulated cortex (bilateral B24, B33), while their increased rCBF in occipital lobe (bilateral B17, B19 and left B18). Additionally, the depression severity was negatively correlated with decreased rCBF in left ventral anterior cingulate cortex B24, and was positively correlated with decreased rCBF in left inferior prefrontal gyrus B47 and increased rCBF in right associative visual cortex B19. The anxiety severity was negatively correlated with decreased rCBF in left subgenual cortex B25. CONCLUSIONS: Although the mechanism underlying the correlation is not yet fully understood, our findings indicated that the rCBF SPECT/CT may provide an objective assessment for MDD severity. It might be used monitoring therapeutic efficacy in the management of MDD.

The remodeling of metabolic brain pattern in patients with extracranial diffuse large B-cell lymphoma.

BACKGROUND: Owing to the advances in diagnosis and therapy, survival or remission rates for lymphoma have improved prominently. Apart from the lymphoma- and chemotherapy-related somatic symptom burden, increasing attention has been drawn to the health-related quality of life. The application of 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET/CT) has been routinely recommended for the staging and response assessment of FDG-avid lymphoma. However, up till now, only a few researches have investigated the brain metabolic impairments in patients with pre-treatment lymphoma. The determination of the lymphoma-related metabolic brain pattern would facilitate exploring the tailored therapeutic regimen to alleviate not only the physiological, but also the psychological symptoms. In this retrospective study, we aimed to establish the diffuse large B-cell lymphoma-related pattern (DLBCLRP) of metabolic brain network and investigate the correlations between DLBCLRP and several indexes of the staging and response assessment. RESULTS: The established DLBCLRP was characterized by the increased metabolic activity in bilateral cerebellum, brainstem, thalamus, striatum, hippocampus, amygdala, parahippocampal gyrus and right middle temporal gyrus and by the decreased metabolic activity in bilateral occipital lobe, parietal lobe, anterior cingulate gyrus, midcingulate cortex and medial frontal gyrus. Significant difference in the baseline expression of DLBCLRP was found among complete metabolic response (CMR), partial metabolic response (PMR) and progressive metabolic disease (PMD) groups (P < 0.01). DLBCLRP expressions were also significantly or tended to be positively correlated with international prognostic index (IPI) (rs = 0.306, P < 0.05), lg(total metabolic tumor volume, TMTV) (r = 0.298, P < 0.05) and lg(total lesion glycolysis, TLG) (r = 0.233, P = 0.064). Though no significant correlation of DLBCLRP expression was found with Ann Arbor staging or tumor SUVmax (P > 0.05), the post-treatment declines of DLBCLRP expression were significantly positively correlated with Ann Arbor staging (rs = 0.284, P < 0.05) and IPI (rs = 0.297, P < 0.05). CONCLUSIONS: The proposed DLBCLRP would lay the foundation for further investigating the cerebral dysfunction related to DLBCL itself and/or treatments. Besides, the expression of DLBCLRP was associated with the tumor burden of lymphoma, implying a potential biomarker for prognosis.

Voxel-based analysis of the metabolic asymmetrical and network patterns in hypermetabolism-associated crossed cerebellar diaschisis.

Crossed cerebellar diaschisis (CCD) has been widely investigated in patients with supratentorial hypometabolism, however, the available evidence about the metabolic feature of CCD in patients with contralateral supratentorial hypermetabolism is lacking. This study aimed to assess the metabolic asymmetrical profile, network pattern and predisposing factors for the hypermetabolism-associated CCD, by using voxel-based asymmetry index (AI) and brain network analyses. Seventy CCD positive (CCD+) and 99 CCD negative (CCD-) patients with unilateral supratentorial hypermetabolism were introduced. Among different brain regions with AImax or AImin, striatum & thalamus was accompanied by the highest positive rate of CCD (85.7% or 70.1%, respectively). CCD+ group had significantly greater AImax (median [IQR], 0.62 [0.44-0.84] vs. 0.47 [0.35-0.61]), supratentorial hypermetabolic volume (1183.5 [399.3-3026.8] vs. 386.0 [152.0-1193.0]) and hypometabolic volume (37796.5 [24741.8-53278.0] vs. 3337.0 [1020.0-17193.0]), and lower AImin (-0.85 [-1.05--0.73] vs. -0.49 [-0.68--0.35]) compared with CCD- group (all P < 0.001). Logistic regression analysis manifested that patients with AImin located at striatum & thalamus were 16.4 times more likely to present CCD than those at frontal lobe (OR = 16.393; 95% CI, 4.463-60.207; P < 0.001), and the occurrence of CCD was also associated with AImax (OR = 49.594; 95% CI, 5.519-445.653; P < 0.001) and AImin (OR = 3.133 × 10-4, 95% CI, 1.693 × 10-5-5.799 × 10-3, P < 0.001). Brain network analysis indicated that the relative hypermetabolism in the contralateral supplementary motor cortex (SMC) and precuneus gyrus were constant in the CCD related patterns. These results demonstrated that the greater AImax, lower AImin and AImin located at striatum & thalamus should be predisposing factors for CCD in patients with unilateral supratentorial hypermetabolism. Relative increased activities in the contralateral SMC and precuneus gyrus might be attributed to a compensatory mechanism for the abnormal brain network related to CCD.

The Anti-Inflammatory Effect of Preventive Intervention with Ketogenic Diet Mediated by the Histone Acetylation of mGluR5 Promotor Region in Rat Parkinson's Disease Model: A Dual-Tracer PET Study.

Materials and Methods: The neuroprotective effect of ketosis state prior to the onset of PD (preventive KD, KDp) was compared with that receiving KD after the onset (therapeutic KD, KDt) in the lipopolysaccharide- (LPS-) induced rat PD model. A total of 100 rats were randomly assigned to the following 4 groups: sham, LPS, LPS + KDp, and LPS + KDt groups. Results: Significant dopamine deficient behaviors (rotational behavior and contralateral forelimb akinesia), upregulation of proinflammatory mediators (TNF-α, IL-1ß, and IL-6), loss of dopaminergic neurons, reduction of mGluR5+ microglia cells, increase of TSPO+ microglia cells, reduction of H3K9 acetylation in the mGluR5 promoter region and mGluR5 mRNA expression, and decline in the phosphorylation levels of Akt/GSK-3ß/CREB pathway were observed after the intervention of LPS (P < 0.01). TSPO and DAT PET imaging revealed the increased uptake of 18F-DPA-714 in substantia nigra and decreased uptake of 18F-FP-CIT in substantia nigra and striatum in LPS-treated rats (P < 0.001). These impairments were alleviated by the dietary intervention of KD, especially with the strategy of KDp (P < 0.05). Conclusions: The anti-inflammatory effect of KD on PD was supposed to be related to the modulation of Akt/GSK-3ß/CREB signaling pathway mediated by the histone acetylation of mGluR5 promotor region. The KD intervention should be initiated prior to the PD onset in high-risk population to achieve a more favorable outcome.

Comparison of 18F-FDG, 68Ga-FAPI, and 68Ga-DOTATATE PET/CT in a Patient With Pancreatic Neuroendocrine Tumor.

ABSTRACT: We present image findings of 18F-FDG, 68Ga-FAPI, and 68Ga-DOTATATE PET/CT in a 35-year-old woman with multiple metastases of pancreatic neuroendocrine tumor. The images of PET/CTs using 3 different tracers all showed multiple foci of increased activities in the liver and pancreas body, in which 68Ga-FAPI PET/CT displayed the highest tumor-to-liver ratios. However, 68Ga-DOTATATE PET/CT detected more small metastatic lymph node and bone metastases, which were missed by both FDG and FAPI PET/CT.

Prostate-specific membrane antigen expression in hepatocellular carcinoma, cholangiocarcinoma, and liver cirrhosis.

BACKGROUND: Primary liver cancer includes three subtypes: Hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (CCA), and combined hepatocellular carcinoma. Patients with primary liver cancer experienced poor prognosis and high mortality, so early detection of liver cancer and improved management of metastases are both key strategies to reduce the death toll from liver cancer. Prostate-specific membrane antigen (PSMA) expression in the tumor-associated neovasculature of nonprostate malignancies including liver cancer has been reported recently, but conclusive evidence of PSMA expression based on the pathological type of liver cancer remains limited. AIM: To study the expression of PSMA in HCC, CCA, and liver cirrhosis. METHODS: A total of 446 formalin-fixed paraffin-embedded (FFPE) liver tumor and liver cirrhosis tissue samples were obtained retrospectively from the Pathology Department of Tongji Hospital. Immunohistochemistry was used to detect PSMA expression in these 446 FFPE liver biopsy specimens (213 HCC, 203 CCA, and 30 liver cirrhosis). The tumor compartment and the associated neovascular endothelium were separately analyzed. PSMA expression was examined by two certified pathologists, and the final results were presented in a 4-point scoring system (0-3 points). Correlation between PSMA expression and clinicopathological information was also assessed. RESULTS: PSMA was expressed primarily in the neovascular endothelium associated with tumors. The positive rate of PSMA staining in HCC was significantly higher than that in CCA (86.8% vs 79.3%; P = 0.001) but was only 6.6% in liver cirrhosis (P = 0.000). HCC cases had more 3-score PSMA staining than CCA had (89/213, 41.8% vs 35/203, 17.2%; P = 0.001). PSMA expression correlated positively with the stage and grade of HCC and CCA. In both liver cancer subtypes, there were more PSMA+ cases in stages III-V diseases than in stages I and II. High staining intensity of PSMA was more frequently observed in liver cancers at high grade and advanced stage. There was no significant association of PSMA expression with sex, age, region, α-fetoprotein, hepatitis B surface antigen, or tumor size in both tumor subtypes. CONCLUSION: Neovascular PSMA may be a promising marker to differentiate HCC from liver cirrhosis and a prognostic marker for anti-tumor angiogenesis therapy for HCC.

Combined clinical parameters improve the diagnostic efficacy of 18F-FDG PET/CT in patients with fever of unknown origin (FUO) and inflammation of unknown origin (IUO): A prospective study in China.

OBJECTIVES: To improve the diagnostic efficacy of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) for Chinese patients with fever of unknown origin (FUO) and inflammation of unknown origin (IUO), with combined clinical parameters. MATERIALS AND METHODS: FUO/IUO patients who underwent a standard diagnostic work-up and 18F-FDG PET/CT scanning were enrolled and divided into a local uptake lesion subgroup and a non-specific abnormal uptake subgroup. Beneficial clinical parameters for improving the diagnostic efficacy of PET/CT were identified. RESULTS: From January 2014 to January 2019, 253 FUO/IUO patients were studied. In total, 147 patients had local uptake lesions and 106 patients had non-specific abnormal uptake. In the local uptake lesion group, the positioning accuracy of PET/CT was 37.2% in grades 1 and 2, and 66.3% in grades 3 and 4. With the following combination of clinical parameters, the positioning accuracy increased to 75.0% and 90.0%, respectively: time from admission to performing PET/CT scanning <6.5 days and C-reactive protein level >95 mg/l. In the non-specific abnormal uptake group, the combination of sex (male), bicytopenia, and lactic dehydrogenase improved the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for diagnosing malignancy from 64.3%, 69%, 60%, and 72.7%, respectively, to 83.3%, 81%, 81.4%, and 82.9%, respectively. With the combination of sex (male), white blood count, serum ferritin level, and hepatosplenomegaly, the infection prediction model had a sensitivity, specificity, PPV, and NPV of 78%, 76.2%, 76.6%, and 77.6%, respectively. CONCLUSIONS: Combined clinical parameters improved the localization diagnostic value of 18F-FDG PET/CT in the local uptake lesion subgroup and the etiological diagnostic value in the non-specific abnormal uptake subgroup.

Concurrent Metastatic Pheochromocytomas and Lung Adenocarcinoma on 18F-FDG and 68Ga-DOTATATE PET/CT Images.

Both F-FDG and Ga-DOTATATE PET/CT are used in the evaluation of pheochromocytomas. We reported F-FDG and Ga-DOTATATE PET/CT findings in a 60-year-old man who had recurrent metastatic pheochromocytoma coexisting with lung adenocarcinoma. The metastatic pheochromocytoma showed increased activity on both F-FDG and Ga-DOTATATE PET/CT, whereas the lung adenocarcinoma lesion showed no obvious DOTATATE activity.

Telbivudine-Induced Myopathy Incidentally Detected by FDG PET/CT Imaging in a Patient With History of Hepatocellular Carcinoma.

Myopathy is an adverse effect of telbivudine. We describe a case of telbivudine-induced myopathy visualized on FDG PET/CT in a 75-year-old man with history of chronic HBV infection and hepatocellular carcinoma. FDG PET/CT images demonstrate no abnormal uptake characteristic of hypermetabolic malignancy. However, intense hypermetabolic activity in muscles of the abdominal wall was noted. Three months after telbivudine withdrawal, a second FDG PET/CT showed normal muscle activity in the abdominal wall.

Anal Malignant Melanoma Manifesting Hepatic Metastases Shown on FDG PET/CT.

Multiple hepatic metastases are uncommon as initial presentation of primary anal malignant melanoma. We report FDG PET/CT findings of pathology-proven hepatic metastases from anal malignant melanoma of unknown origin in a 43-year-old woman whose initial presentation was worsening abdominal pain.

Elevated 68Ga-DOTATATE Activity in IgG4-Related Lymphadenopathy.

Ga-DOTATATE PET/CT was performed in a 60-year-old man to detect culprit tumor responsible for tumor-induced osteomalacia (TIO). The images revealed multiple foci of abnormal activity in soft tissue lesion, which were not typical of tumor causing TIO in Ga-DOTATATE PET/CT. Considering other neoplastic processes, FDG PET/CT were subsequently performed, which showed all same lesions, although the lesions with highest activity were different between the scans. Pathological examination demonstrated that the patient experienced TIO caused by 1 lesion, but other lesions were due to IgG4-related lymphadenopathy.

Prognostic Value of 99mTc-Sestamibi Parathyroid Scintigraphy in Predicting Future Surgical Eligibility in Patients With Asymptomatic Primary Hyperparathyroidism.

PURPOSE: Patients with asymptomatic primary hyperparathyroidism might have a positive Tc-sestamibi parathyroid but do not meet criteria for surgical resection when the disease is diagnosed. However, many of these asymptomatic patients will become symptomatic or meet criteria for surgery later on. The aim of this study was to determine whether a positive sestamibi scan can precede future surgical eligibility in these patients. METHODS: This retrospective study reviewed the records of 94 asymptomatic patients who had hyperparathyroidism and underwent Tc-sestamibi study with SPECT/CT imaging. Among them, 35 patients, including 12 with positive and 23 with negative sestamibi parathyroid scan, did not meet the criteria for surgery at the time of imaging, and follow-up record for at least 1 year was assessed on these patients. The imaging findings and the eligibility for surgery at the end of the follow-up were compared. RESULTS: With a median follow-up of 2.4 years (range, 1-4 years), among all 35 patients who were initially not eligible for surgery, 6 of 12 patients with a positive sestamibi scan became eligible for surgery, whereas 20 of 23 patients with negative scans remained ineligible for surgery. CONCLUSIONS: Positive parathyroid SPECT/CT predicted a higher possibility of meeting surgical criteria over time in asymptomatic hyperparathyroidism patients who are not surgery eligible at the time of presentation.