Development and evaluation of a new high-TOF-resolution all-digital brain PET system.

Objective.Time-of-flight (TOF) capability and high sensitivity are essential for brain-dedicated positron emission tomography (PET) imaging, as they improve the contrast and the signal-to-noise ratio (SNR) enabling a precise localization of functional mechanisms in the different brain regions.Approach.We present a new brain PET system with transverse and axial field-of-view (FOV) of 320 mm and 255 mm, respectively. The system head is an array of 6 × 6 detection elements, each consisting of a 3.9 × 3.9 × 20 mm3lutetium-yttrium oxyorthosilicate crystal coupled with a 3.93 × 3.93 mm2SiPM. The SiPMs analog signals are individually digitized using the multi-voltage threshold (MVT) technology, employing a 1:1:1 coupling configuration.Main results.The brain PET system exhibits a TOF resolution of 249 ps at 5.3 kBq ml-1, an average sensitivity of 22.1 cps kBq-1, and a noise equivalent count rate (NECR) peak of 150.9 kcps at 8.36 kBq ml-1. Furthermore, the mini-Derenzo phantom study demonstrated the system's ability to distinguish rods with a diameter of 2.0 mm. Moreover, incorporating the TOF reconstruction algorithm in an image quality phantom study optimizes the background variability, resulting in reductions ranging from 44% (37 mm) to 75% (10 mm) with comparable contrast. In the human brain imaging study, the SNR improved by a factor of 1.7 with the inclusion of TOF, increasing from 27.07 to 46.05. Time-dynamic human brain imaging was performed, showing the distinctive traits of cortex and thalamus uptake, as well as of the arterial and venous flow with 2 s per time frame.Significance.The system exhibited a good TOF capability, which is coupled with the high sensitivity and count rate performance based on the MVT digital sampling technique. The developed TOF-enabled brain PET system opens the possibility of precise kinetic brain PET imaging, towards new quantitative predictive brain diagnostics.

Effects of STN-DBS surgery on cerebral glucose metabolism and distribution of DAT in Parkinson's disease.

INTRODUCTION: Parkinson's disease (PD) is a neurodegenerative disorder that affects millions of people worldwide. Subthalamic nucleus (STN) deep brain stimulation (DBS) has been shown to be an effective treatment for PD; however, the effects of this surgery on cerebral metabolism and presynaptic dopamine transporter (DAT) distribution are still being studied. METHODS: In this study, we included 12 PD patients (6 male and 6 female) who underwent STN-DBS surgery and had both 18 F-FDG and 11 C-CFT PET/CT imaging before and 1 year after the surgery. We used paired t-tests to identify changes in cerebral metabolism and calculated PD-related metabolic covariance pattern (PDRP) scores. We also assessed the uptake of 11 C-CFT in the striatum using striatal-to-occipital ratios (SORs). RESULTS: One year after surgery, we observed significant reductions in tremor, rigidity, akinesia, postural instability/gait disturbance, and Unified Parkinson's Disease Rating Scale Part III scores (p < .01, p < .001, p < .001, p < .001, and p < .001, respectively). Hamilton Depression Rating Scale and quality of life (PDQ-39 SI) were also significantly reduced (p < .05 and p < .01, respectively). The mean PDRP score decreased by 37% from 13.0 ± 6.6 to 8.2 ± 7.9 after STN-DBS surgery (p < .05). We observed decreased 18 F-FDG uptake in several areas, including the temporal lobe (BA22), thalamus, putamen, and cingulate gyrus (BA24), whereas it was increased in the supplementary motor area, postcentral gyrus, lingual gyrus, and precuneus (p < .05). SORs of 11 C-CFT in the bilateral caudate nucleus and ipsilateral posterior putamen were significantly decreased compared to preoperative levels (p < .05). CONCLUSION: Our findings suggest that STN-DBS surgery modifies the metabolic network of PD patients and improves motor symptoms, depression, and quality of life. However, it does not prevent the decrease of DAT in striatal areas.

Biodistribution and radiation dosimetry in cancer patients of the ascorbic acid analogue 6-Deoxy-6-[18F] fluoro-L-ascorbic acid PET imaging: first-in-human study.

PURPOSE: Clinical studies on the use of ascorbic acid (AA) have become a hot spot in cancer research. There remains an unmet need to assess AA utilization in normal tissues and tumors. 6-Deoxy-6-[18F]fluoro-L-ascorbic acid ([18F]DFA) displayed distinctive tumor localization and similar distribution as AA in mice. In this study, to evaluate the distribution, tumor detecting ability and radiation dosimetry of [18F]DFA in humans, we performed the first-in-human PET imaging study. METHODS: Six patients with a variety of cancers underwent whole-body PET/CT scans after injection of 313-634 MBq of [18F]DFA. Five sequential dynamic emission scans in each patient were acquired at 5-60 min. Regions of interest (ROI) were delineated along the edge of the source-organ and tumor on the transverse PET slice. Tumor-to-background ratio (TBR) was obtained using the tumor SUVmax to background SUVmean. Organ residence times were calculated via time-activity curves, and human absorbed doses were estimated from organ residence time using the medical internal radiation dosimetry method. RESULTS: [18F]DFA was well tolerated in all subjects without serious adverse event. The high uptake was found in the liver, adrenal glands, kidneys, choroid plexus, and pituitary gland. [18F]DFA accumulated in tumor rapidly and the TBR increased over time. The average SUVmax of [18F]DFA in tumor lesions was 6.94 ± 3.92 (range 1.62-22.85, median 5.94). The organs with the highest absorbed doses were the liver, spleen, adrenal glands, and kidneys. The mean effective dose was estimated to be 1.68 ± 0.36 E-02 mSv/MBq. CONCLUSIONS: [18F]DFA is safe to be used in humans. It showed a similar distribution pattern as AA, and displayed high uptake and retention in tumors with appropriate kinetics. [18F]DFA might be a promising radiopharmaceutical in identifying tumors with high affinity for SVCT2 and monitoring AA distribution in both normal tissues and tumors. TRIAL REGISTRATION: Chinese Clinical Trial Registry; Registered Number: ChiCTR2200057842 (registered 19 March 2022).

Mitochondrial respiration inhibitor enhances the anti-tumor effect of high-dose ascorbic acid in castration-resistant prostate cancer.

Previous evidences have demonstrated that anti-tumor effect of high-dose ascorbic acid is associated with the generation of reactive oxygen species (ROS) via autoxidation. Hypoxia induces therapy resistance in castration-resistant prostate cancer. As a mitochondrial respiration inhibitor, metformin has the potential to improve tumor oxygenation. In this study, we evaluate the anti-tumor effect of ascorbic acid combined with metformin in prostate cancer. We demonstrated that ascorbic acid inhibits prostate cancer cells proliferation by generating ROS, and metformin enhances the anti-tumor effects of ascorbic acid. Mechanistically, metformin reduces oxygen consumption rate and NADP+/NADPH value in prostate cancer cells, thereby increases the ROS content induced by ascorbic acid. In addition, our data demonstrated that ascorbic acid inhibits p-AKT signaling in a ROS-dependent pathway, leading to inhibition of p-mTOR expression. And metformin inhibits the p-mTOR expression by activating the AMPK signaling pathway, exerting a synergistic effect on tumor suppression with ascorbic acid. Furthermore, metformin improves tumor oxygenation, and the combined treatment effect of ascorbic acid and metformin were demonstrated in a xenograft model of prostate cancer. Taken together, our data demonstrate that metformin enhances the anti-tumor proliferation effect of ascorbic acid by increasing ROS content in castration-resistant prostate cancer. This provides a new strategy for the clinical application of high-dose ascorbic acid as an anti-tumor drug. KEY MESSAGES: Ascorbic acid inhibits tumor growth by inducing ROS generation. As a mitochondrial respiration inhibitor, metformin inhibits cellular oxygen consumption rate to improve oxygenation of prostate cancer. Metformin enhances anti-tumor effect of ascorbic acid by increasing ROS content. Ascorbic acid inhibits the mTOR expression via PI3K-AKT pathway, and metformin inhibits the mTOR expression by inhibiting AMPK signaling in prostate cancer cells.

Role of Fe, Transferrin and Transferrin Receptor in Anti-Tumor Effect of Vitamin C.

High-dose vitamin C (VC) exhibits anti-tumor effects, and the cytotoxicity of VC is correlated with oxidative stress. However, iron, as a redox metal, plays an important effect in redox cycling and free radical formation in cells. This study addresses the role of iron ion in the cytotoxicity of VC. We found that iron supplementation increases the anti-tumor effect of VC, which was influenced by the cellular iron uptake pathway-transferrin (TF)/transferrin receptor (TFR) system. The TFR expression of tumors can be assessed by 68Ga-citrate PET imaging, and it would be helpful to screen out the tumor type which is more sensitive to VC combined with an iron supplementation treatment.

Comparison of 18 F-DOPA and 18 F-DTBZ for PET/CT Imaging of Idiopathic Parkinson Disease.

OBJECTIVE: The aim of this study was to compare 2 imaging tracers, 18 F-DOPA and 18 F-DTBZ, for PET/CT imaging in idiopathic Parkinson disease (PD). METHODS: We recruited 32 PD patients and 12 healthy controls in this study. All subjects underwent both 18 F-DOPA and 18 F-DTBZ PET/CT, and the results were interpreted by visual analysis and semiquantitative analysis (specific uptake ratios [SURs]). A 1-way analysis of variance was used to compare the clinical data and the SURs among the patients at different stages. Regression analysis was performed to analyze the correlation between the SURs and the clinical data. RESULTS: Among the PD patients, there were 7 patients in Hoehn and Yahr stage I, 14 patients in stage II, and 11 patients in stage III. Linear correlation was found in striatal SURs between the 2 tracers ( P < 0.05). In patients of early stages, the striatal SUR decrease percent of 2 tracers had no statistical difference (paired t test, P > 0.05). By initial visual analysis, all the patients were interpreted as positive with 18 F-DBTZ (6 unilaterally, 26 bilaterally), and 31 cases were regarded as positive with 18 F-DOPA (8 unilaterally, 23 bilaterally). After setting the upper limit of SUR images with the putamen SURs of healthy controls (SUR T ), all patients were interpreted as positive with both tracers ( 18 F-DTBZ: 5 unilaterally, 27 bilaterally; 18 F-DOPA: 4 unilaterally, 28 bilaterally). CONCLUSION: 18 F-DTBZ and 18 F-DOPA could reflect the same level of dopaminergic neuron degeneration for PD in early stages, and they have the consistent visual analysis results.

Corticostriatal Hypermetabolism in Moyamoya Disease-Induced Hemichorea: Two Case Reports and a Literature Review.

Moyamoya disease (MMD) is a rare cause of chorea, and its pathophysiological mechanism remains unclear. We explore the use of cerebral positron emission tomography (PET) to study brain functional connectivity in 2 patients with MMD-induced hemichorea. Abnormal metabolism of brain was analyzed by 18F-fluorodeoxyglucose (18F-FDG) PET images. Dopamine transporters (DAT) PET evaluated the integrity of the cerebral dopamine system. A comprehensive systemic literature search of the PubMed database was also conducted. The 18F-FDG imaging of our patients showed no responsible hypometabolism in affected brain areas, while hypermetabolism in the affected caudate nucleus, putamen and fronto-parietal areas could be seen. DAT PET imaging was normal in patient 1 (a 23-year-old woman), while remarkably reduced DAT binding was seen in the left striatum of patient 2 (a 48-year-old woman). The literature review of 9 publications revealed that 11 patients who underwent single photon emission computed tomography (SPECT) showed cerebral hypoperfusion in the cortex and subcortical area; 18F-FDG PET was performed in 3 cases, which revealed hypermetabolism in the affected striatum in 2 cases. These findings suggest that the striatal and cortical hypermetabolism in the first patient result from underactivity in indirect pathway from basal ganglia-thalamocortical circuits, causing increased activity of excitatory glutamatergic thalamostriatal and thalamocortical projection neurons. The collateral vessels in the basal ganglia might lead to disruption of normal basal ganglia signaling. A dominant left hemisphere with corpus callosal connections to the right basal ganglia resulting into left hemichorea is the most probable explanation for the second patient. We have identified abnormal functional connectivity in basal ganglia-thalamocortical circuits in patients with MMD-induced chorea highlighting the corticostriatal pathway plays an important role in the pathogenesis of MMD-induced chorea.

Pharmacological Vitamin C Treatment Impedes the Growth of Endogenous Glutamine-Dependent Cancers by Targeting Glutamine Synthetase.

Purpose: Glutamine synthetase (GS) is the only currently known enzyme responsible for synthesizing endogenous glutamine (Gln). GS exerts a critical role in the oncogenesis of endogenous Gln-dependent cancers, making it an attractive target for anti-tumor therapies. A mixed-function oxidation system consisting of vitamin C (VC), oxygen, and trace metals can oxidize GS and promote its degradation. The current study aims to explore the effect of pharmacological VC treatment on GS. Methods: Endogenous Gln-dependent cancer lines (breast cancer MCF7 and prostate cancer PC3) were selected to establish chronic Gln-deprived MCF7 and PC3 cell models. The expression of GS in parental and chronic Gln-deprived tumor cells exposed to VC treatment and control was determined by Western blot analysis. The anti-cancer effects of VC on parental and chronic Gln-deprived tumor cells were assessed by CCK-8 and annexin V-FITC/PI FACS assays. In addition, changes in cellular reactive oxygen species (ROS), glutathione (GSH) levels and NADPH/NADP + ratio were analyzed to explore the underlying mechanisms. Moreover, BALB/c nude mice xenografting with parental and chronic Gln-deprived prostate cancer cells were constructed to evaluate the in vivo therapeutic effect of VC. Finally, tumor 13N-ammonia uptake in mice bearing prostate cancer xenografts was analyzed following treatment with VC and the expression of GS in xenografts were detected by immunohistochemistry. Results: Cells overexpressing GS were obtained by chronic Gln deprivation. We found that the cytotoxic effect of VC on cancer cells was positively correlated with the expression of GS. Additionally, VC treatment led to a significant increase in ROS production, as well as GSH depletion and NADPH/NADP + reduction. These changes could be reversed by the antioxidant N-acetyl-L-cysteine (NAC). Furthermore, pharmacological VC treatment exhibited a more significant therapeutic effect on xenografts of prostate cancer cells overexpressing GS, that could be well monitored by 13N-ammonia PET/CT imaging. Conclusion: Our findings indicate that VC can kill cancer cells by targeting glutamine synthetase to induce oxidative stress. VC could be used as an anti-cancer treatment for endogenous glutamine-dependent cancers.

Co-registration Analysis of Fluorodopa and Fluorodeoxyglucose Positron Emission Tomography for Differentiating Multiple System Atrophy Parkinsonism Type From Parkinson's Disease.

It is difficult to differentiate between Parkinson's disease and multiple system atrophy parkinsonian subtype (MSA-P) because of the overlap of their signs and symptoms. Enormous efforts have been made to develop positron emission tomography (PET) imaging to differentiate these diseases. This study aimed to investigate the co-registration analysis of 18F-fluorodopa and 18F-flurodeoxyglucose PET images to visualize the difference between Parkinson's disease and MSA-P. We enrolled 29 Parkinson's disease patients, 28 MSA-P patients, and 10 healthy controls, who underwent both 18F-fluorodopa and 18F-flurodeoxyglucose PET scans. Patients with Parkinson's disease and MSA-P exhibited reduced bilateral striatal 18F-fluorodopa uptake (p < 0.05, vs. healthy controls). Both regional specific uptake ratio analysis and statistical parametric mapping analysis of 18F-flurodeoxyglucose PET revealed hypometabolism in the bilateral putamen of MSA-P patients and hypermetabolism in the bilateral putamen of Parkinson's disease patients. There was a significant positive correlation between 18F-flurodeoxyglucose uptake and 18F-fluorodopa uptake in the contralateral posterior putamen of MSA-P patients (rs = 0.558, p = 0.002). Both 18F-flurodeoxyglucose and 18F-fluorodopa PET images showed that the striatum was rabbit-shaped in the healthy control group segmentation analysis. A defective rabbit-shaped striatum was observed in the 18F-fluorodopa PET image of patients with Parkinson's disease and MSA-P. In the segmentation analysis of 18F-flurodeoxyglucose PET image, an intact rabbit-shaped striatum was observed in Parkinson's disease patients, whereas a defective rabbit-shaped striatum was observed in MSA-P patients. These findings suggest that there were significant differences in the co-registration analysis of 18F-flurodeoxyglucose and 18F-fluorodopa PET images, which could be used in the individual analysis to differentiate Parkinson's disease from MSA-P.

Diagnostic efficiency of 68Ga-DOTANOC PET/CT in patients with suspected tumour-induced osteomalacia.

OBJECTIVES: Currently, the main challenge in tumour-induced osteomalacia (TIO) is the difficulty in locating culprit tumours for definitive diagnosis and surgical therapy. Herein, we retrospectively evaluate the efficiency of 68Ga-DOTANOC PET/CT in the localisation and diagnosis of TIO, and compared with 18F-FDG. METHODS: Twenty-four consecutive patients with hypophosphataemic osteomalacia (HO) and suspicion of TIO who were referred to our centre for 68Ga-DOTANOC PET/CT scanning were retrospectively reviewed. The images were evaluated qualitatively as well as semi-quantitatively, and imaging results were compared with the final diagnoses. RESULTS: Among the total of 21 patients who were included in the final analyses, 17 were diagnosed with TIO, while four were proven to have other causes of HO. 68Ga-DOTANOC PET/CT produced positive results in 16 of the 17 patients with TIO, representing a sensitivity of 94.1%. Moreover, the 68Ga-DOTANOC PET/CT results were negative in 3 of the 4 patients without TIO, representing a specificity of 75.0%. The overall accuracy of 68Ga-DOTANOC PET/CT in locating the tumours responsible for TIO is 90.5%. In particular, 68Ga-DOTANOC PET/CT detected the culprit tumours in 4 out of 10 patients with negative results on previous 18F-FDG PET/CT and showed a significantly higher T/M ratio of tumours than 18F-FDG PET/CT in the same patients (n = 10; 4.76 ± 3.08 vs 1.95 ± 1.33, p < 0.05). CONCLUSIONS: 68Ga-DOTANOC PET/CT is an accurate imaging modality in the localisation of tumours for TIO. It is superior to 18F-FDG PET/CT and may be useful in the differential diagnosis of HO. KEY POINTS: • TIO should be considered a possible cause for patients diagnosed with HO, which usually needs to be differentiated from other aetiologies. • 68Ga-DOTANOC PET/CT is an accurate imaging modality in locating culprit tumours for TIO, superior to 18F-FDG PET/CT.

Increased Tumoral Microenvironmental pH Improves Cytotoxic Effect of Pharmacologic Ascorbic Acid in Castration-Resistant Prostate Cancer Cells.

BACKGROUND: The anticancer potential of pharmacologic ascorbic acid (AA) has been detected in a number of cancer cells. However, in vivo study suggested a strongly reduced cytotoxic activity of AA. It was known that pH could be a critical influencing factor for multiple anticancer treatments. In this study, we explored the influence of pH on the cytotoxicity of ascorbic acid. We employed castration-resistant prostate cancer (CRPC) cell lines PC3 and DU145 to observe the therapeutic effect of AA on PCa cells that were cultured with different pH in vitro. We also analyzed the influence of pH and extracellular oxidation on cytotoxicity of AA in cancer cells using reactive oxygen species (ROS) assay, cellular uptake of AA, and NADPH assay. Male BALB/c nude mice bearing prostate carcinoma xenografts (PC3 or DU145) were used to assess treatment response to AA with or without bicarbonate in vivo. The cellular uptake of AA in PCa xenografts was detected using positron emission tomography (PET). Small animal PET/CT scans were performed on mice after the administration of 6-deoxy-6-[18F] fluoro-L-ascorbic acid (18F-DFA). RESULTS: Our in vitro studies demonstrate that acidic pH attenuates the cytotoxic activity of pharmacologic ascorbic acid by inhibiting AA uptake in PCa cells. Additionally, we found that the cancer cell-selective toxicity of AA depends on ROS. In vivo, combination of AA and bicarbonate could provide a significant better therapeutic outcome in comparison with controls or AA single treated mice. 18F-DFA PET imaging illustrated that the treatment with NaHCO3 could significantly increase the AA uptake in tumor. CONCLUSIONS: The alkalinity of tumor microenvironment plays an important role in anticancer efficiency of AA in CRPC. 18F-DFA PET/CT imaging could predict the therapeutic response of PCa animal model through illustration of tumoral uptake of AA. 18F-DFA might be a potential PET tracer in clinical diagnosis and treatment for CRPC.

Differentiation of suprasellar meningiomas from non-functioning pituitary macroadenomas by 18F-FDG and 13N-Ammonia PET/CT.

BACKGROUND: Differentiation of suprasellar meningiomas (SSMs) from non-functioning pituitary macroadenomas (NFPMAs) is useful for clinical management. We investigated the utility of 13N-ammonia combined with 18F-FDG positron emission tomography (PET)/computed tomography (CT) in distinguishing SSMs from NFPMAs retrospectively. METHODS: Fourteen NFPMA patients and eleven SSM patients with histopathologic diagnosis were included in this study. Every patient underwent both 18F-FDG and 13N-ammonia PET/CT scans. The tumor to gray matter (T/G) ratios were calculated for the evaluation of tumor uptake. RESULTS: The uptake of 18F-FDG was higher in NFPMAs than SSMs, whereas the uptake of 13N-ammonia was obviously lower in NFPMAs than SSMs. The differences of 18F-FDG and 13N-ammonia uptake between the two groups were significant respectively (0.92[0.46] vs 0.59[0.29], P < 0.05, 18F-FDG; 1.58 ± 0.56 vs 2.80 ± 1.45, P < 0.05, 13N-ammonia). Tumor classification demonstrated a high overall accuracy of 96.0% for differential diagnosis. When the two traces were combined, only 1 SSM was misclassified into the NFPMA group. CONCLUSION: SSMs and NFPMAs have different metabolic characteristics on 18F-FDG and 13N-ammonia PET images. The combination of these two tracers can effectively distinguish SSMs from NFPMAs.

The Xc- inhibitor sulfasalazine improves the anti-cancer effect of pharmacological vitamin C in prostate cancer cells via a glutathione-dependent mechanism.

PURPOSE: Traditional treatment regimens for advanced prostate cancer, especially castration-resistant prostate cancer, result in low survival times with severe side effects. Therefore, new treatment options are required. Vitamin C (VC) has been identified as a promising anti-cancer agent of which the effects depend on the accumulation of H2O2 that is produced through autoxidation. Sulfasalazine (SAS), a cystine transporter (Xc-) inhibitor, is known to suppress cellular glutathione (GSH) biosynthesis. Here, we hypothesized that targeting the Xc- transporter via SAS may improve the anti-cancer activity of VC through regulating GSH biosynthesis, which in turn may result in the accumulation of reactive oxygen species (ROS). METHODS: The anti-cancer effect of VC and/or SAS on prostate cancer cells was assessed using WST-8, colony formation and annexin V-FITC/PI FACS assays. Changes in cellular ROS and GSH levels were determined to verify our hypothesis. Finally, BALB/c nude mice bearing prostate cancer xenografts were used to assess the anti-cancer effects of single or combined VC and SAS therapies. RESULTS: We found that SAS could potentiate the short- and long-term cytotoxicity of VC in prostate cancer cells. We also found that the synergistic effect of SAS and VC led to significant cellular GSH depletion, resulting in increased ROS accumulation. This synergistic effect could be reversed by the antioxidant N-acetyl-L-cysteine (NAC). The synergistic effect of SAS and VC was also noted in prostate cancer xenografts and correlated with immunohistochemistry results. CONCLUSIONS: Our results strongly indicate that SAS, a relatively non-toxic drug that targets cystine transporters, in combination with VC may be superior to their single applications in the treatment of prostate cancer.

Decreased Striatal Vesicular Monoamine Transporter Type 2 Correlates With the Nonmotor Symptoms in Parkinson Disease.

OBJECTIVE: Nonmotor symptoms (NMS) are critical players in the patients' quality of life in Parkinson disease (PD). Vesicular monoamine transporter type 2 (VMAT2) has been reported owing to a role in affecting dopamine neurons in the striatum. Therefore, this study set out to characterize the relationship between VMAT2 distribution in the striatum in relation to the NMS in PD. METHODS: Totally, 21 age-matched normal controls and 37 patients with PD in the moderate stages were included, followed by examination using F-DTBZ (F-AV133) PET/CT. The specific uptake ratio (SUR) of each striatal subregion was then determined with the occipital cortex as the reference background region. The overall NMSs of each individual patient were evaluated. Finally, the role of the striatal SURs in the clinical symptom scores were evaluated through the application of a Spearman correlation analysis as well as a multivariable stepwise regression analysis. RESULTS: Patients with PD, particularly those at a more advanced stage, exhibited a more pronounced reduction in SURs in the bilateral putamen and caudate nucleus (P < 0.05, vs healthy controls). Meanwhile, patients at more advanced PD stages were found to have significantly worse scores in NMS except cognitive function. The Spearman correlation analysis demonstrated that NMS scores, with the exception of cognition scores, were correlated with striatal SURs (P < 0.05). CONCLUSION: The key findings of the study identified a correlation between decreased striatal VMAT2 with a broad spectrum of NMS in patients with PD, highlighting the association between diminished dopamine supply and the development of NMS in PD.

Diagnostic accuracy of 13N-ammonia PET, 11C-methionine PET and 18F-fluorodeoxyglucose PET: a comparative study in patients with suspected cerebral glioma.

BACKGROUND: The treatment of patients with glioma depended on the nature of the lesion and on histological grade of the tumor. Positron emission tomography (PET) using 13N-ammonia (NH3), 11C-methionine (MET) and 18F-fluorodeoxyglucose (FDG) have been used to assess brain tumors. Our aim was to compare their diagnostic accuracies in patients with suspected cerebral glioma. METHODS: Ninety patients with suspicion of glioma based on previous CT/MRI, who underwent NH3 PET, MET PET and FDG PET, were prospectively enrolled in the study. The reference standard was established by histology or clinical and radiological follow-up. Images were interpreted by visual evaluation and semi-quantitative analysis using the lesion-to-normal white matter uptake ratio (L/WM ratio). RESULTS: Finally, 30 high-grade gliomas (HGG), 27 low-grade gliomas (LGG), 10 non-glioma tumors and 23 non-neoplastic lesions (NNL) were diagnosed. On visual evaluation, sensitivity and specificity for differentiating tumors from NNL were 62.7% (42/67) and 95.7% (22/23) for NH3 PET, 94.0% (63/67) and 56.5% (13/23) for MET PET, and 35.8% (24/67) and 65.2% (15/23) for FDG PET. On semi-quantitative analysis, brain tumors showed significantly higher L/WM ratios than NNL both in NH3 and MET PET (both P < 0.001). The sensitivity, specificity and the area under the curve (AUC) by receiver operating characteristic (ROC) analysis, respectively, were 64.2, 100% and 0.819 for NH3; and 89.6, 69.6% and 0.840 for MET. Besides, the L/WM ratios of NH3, MET and FDG PET in HGG all significantly higher than that in LGG (all P < 0.001). The predicted (by ROC) accuracy of the tracers (AUC shown in parentheses) were 86.0% (0.896) for NH3, 87.7% (0.928) for MET and 93.0% (0.964) for FDG. While no significant differences in the AUC were seen between them. CONCLUSION: NH3 PET has remarkably high specificity for the differentiation of brain tumors from NNL, but low sensitivity for the detection of LGG. MET PET was found to be highly useful for detection of brain tumors. However, like FDG, high MET uptake is frequently observed in some NNL. NH3, MET and FDG PET all appears to be valuable for evaluating the histological grade of gliomas.

The combination of 13N-ammonia and 18F-FDG PET/CT in the identification of metabolic phenotype of primary human brain tumors.

AIM: This pilot study made a preliminary attempt to distinguish different metabolic phenotypes of primary human brain tumors with dual tracer 13N-ammonia and 18F-FDG. METHODS: 74 patients were included in this study including 12 benign meningiomas (B-MEN), 4 malignant meningiomas (M-MEN), 15 low-grade gliomas (LGG), 32 high-grade gliomas (HGG) and 11 primary central nervous system lymphomas (PCNSL). All patients underwent 13N-ammonia and 18F-FDG PET imaging. Semi-quantification analysis by tumor-to-gray matter (T/G) ratios was used for the evaluation of tracer uptakes. After the calculation of canonical discriminant functions, cross validation was done for all cases to evaluate the differential efficacy of dual tracers. RESULTS: According to the visual analysis, B-MEN were characterized by lower uptake of 18F-FDG and higher uptake of 13N-ammonia, while PCNSLs displayed contrary results. Both M-MEN and HGG had higher uptake of 18F-FDG and 13N-ammonia, while LGG displayed negative results for both tracers. According to the T/G ratios analysis, the accuracy of predicted tumor classification by means of canonical discriminant analysis for B-MEN, LGG, HGG and PCNSL was 91.7 %, 100 %, 84.4 % and 93.3 % respectively; the overall accuracy was 90.5 %. CONCLUSION: The combination of dual tracer 13N-ammonia and 18F-FDG has a certain potential in distinguishing different types of brain tumors (meningiomas, gliomas and PCNSL). However, an advantage of the additional use of 13N-ammonia PET compared to a combined diagnosis with MRI and 18F-FDG PET could not be demonstrated and requires further studies.

The role of 13N-ammonia in the differential diagnosis of gliomas and brain inflammatory lesions.

OBJECTIVE: To investigate the utility of 13N-ammonia PET/CT imaging in the differential diagnosis of gliomas and brain inflammations. METHODS: 13N-ammonia PET/CT imaging data of 77 patients with gliomas and 34 patients with brain inflammations were retrospectively analyzed. No patients received any treatment before 13N-ammonia imaging. All the patients were diagnosed by stereotactic biopsy or clinical follow-up. Visual and semi-quantitative analysis was performed to analyze the results of 13N-ammonia imaging. Finally, the uptake ratios of each lesion were calculated and its differences among different groups were tested with one-way ANOVA. RESULTS: 29.4% inflammations, 51.6% low-grade gliomas and 91.3% high-grade gliomas were positive by visual analysis in 13N-ammonia imaging. The sensitivity, specificity and accuracy for the diagnosis of gliomas were 75.3%, 55.8% and 67.8%, respectively. As for semi-quantitative analysis, the T/G ratios of inflammatory lesions, low-grade gliomas and high-grade gliomas were 0.88 ± 0.24, 1.04 ± 0.43 and 1.43 ± 0.49, respectively. One-way ANOVA revealed that the T/G ratios of high-grade gliomas were significantly higher than those of low-grade gliomas and inflammations (P < 0.05), but there was no statistical difference between low-grade gliomas and inflammations (P = 0.118). Among the inflammatory lesions, T/G ratios were not statistically different between infectious and demyelinating lesions (P > 0.05). ROC curve analysis showed that the optimal cut-off value of T/G ratio in distinguishing gliomas from inflammations was 1.21 with the AUC 0.78. The sensitivity, specificity, accuracy, PPV and NPV were 52.9%, 94.4%, 65.3%, 95.7% and 45.9%, respectively. ROC curve analysis showed that the optimal cut-off value of T/G ratio in distinguishing high-grade gliomas from low-grade gliomas was 1.06 with the AUC 0.78. The sensitivity, specificity, accuracy, PPV and NPV were 81.5%, 67.7%, 76.5%, 81.5% and 67.7%, respectively. ROC curve analysis showed that the optimal cut-off value of T/G ratio in distinguishing high-grade gliomas from low-grade gliomas and inflammations was 1.19 with the AUC 0.84. The sensitivity, specificity, accuracy, PPV and NPV were 70.4%, 85.1%, 78.5%, 79.2% and 78.1%, respectively. CONCLUSIONS: 13N-ammonia imaging is effective in distinguishing high-grade gliomas from low-grade gliomas and inflammations, but its role in the differential diagnosis of low-grade gliomas and brain inflammatory lesions is limited, and the accuracy needs to be improved.

Recurrent Scapular Metastasis From Hepatoblastoma Shown on FDG PET/CT and F-DOPA PET/CT.

We report the case of a 4-year-old girl with a biochemical relapse (plasma α-fetoprotein of 57,987.6 µg/L) after hepatoblastoma and extrahepatic metastases removal and adjuvant chemotherapy. Abdominal ultrasound, CT, and MRI failed to determine the site of recurrence. F-FDG PET/CT showed increased activity in the region of left scapula and adjacent soft tissue, which was incorrectly interpreted as the postoperative repair or inflammatory change. F-DOPA PET/CT showed increased activity and noticeable progressed lesion in the same place. Finally, the left scapula was identified as the site of recurrent metastasis from hepatoblastoma by pathological examination.

Cerebral Reorganization in Subacute Stroke Survivors after Virtual Reality-Based Training: A Preliminary Study.

BACKGROUND: Functional magnetic resonance imaging (fMRI) is a promising method for quantifying brain recovery and investigating the intervention-induced changes in corticomotor excitability after stroke. This study aimed to evaluate cortical reorganization subsequent to virtual reality-enhanced treadmill (VRET) training in subacute stroke survivors. METHODS: Eight participants with ischemic stroke underwent VRET for 5 sections per week and for 3 weeks. fMRI was conducted to quantify the activity of selected brain regions when the subject performed ankle dorsiflexion. Gait speed and clinical scales were also measured before and after intervention. RESULTS: Increased activation in the primary sensorimotor cortex of the lesioned hemisphere and supplementary motor areas of both sides for the paretic foot (p < 0.01) was observed postintervention. Statistically significant improvements were observed in gait velocity (p < 0.05). The change in voxel counts in the primary sensorimotor cortex of the lesioned hemisphere is significantly correlated with improvement of 10 m walk time after VRET (r = -0.719). CONCLUSIONS: We observed improved walking and increased activation in cortical regions of stroke survivors after VRET training. Moreover, the cortical recruitment was associated with better walking function. Our study suggests that cortical networks could be a site of plasticity, and their recruitment may be one mechanism of training-induced recovery of gait function in stroke. This trial is registered with ChiCTR-IOC-15006064.

PET-CT for Evaluation of Spleen and Liver 18F-FDG Diffuse Uptake Without Lymph Node Enlargement in Lymphoma.

The aim of the study was to compare differences between lymphoma and inflammation as indicated by high diffuse uptake of F-fluorodeoxyglucose (F-FDG) in the spleen, liver, and bone marrow without increased F-FDG uptake in the lymph nodes and without enlarged peripheral lymph nodes.Eighteen lymphoma patients and 14 inflammation patients were examined with F-FDG positron emission tomography-computer tomography (PET-CT). All patients displayed high diffuse uptake of F-FDG in the spleen, liver, and bone marrow without increased F-FDG uptake in the lymph nodes and without enlarged peripheral lymph nodes. Our analyses compared the maximum standardized uptake values (SUVmax) of F-FDG uptake ratios between the spleen/liver, the spleen/bone marrow, and the liver/bone marrow and further compared spleen sizes between lymphoma and inflammation patients.Using Student t test, no significant differences were found in the SUVmax ratios of spleen/liver and liver/bone marrow between the lymphoma and inflammation patients (t = 0.853, P = 0.401 > 0.05; t = 1.622, P = 0.115 > 0.05). However, the SUVmax ratio of the spleen/bone marrow of the lymphoma patients was significantly different from that of the inflammation patients (t = 2.426, P = 0.021 < 0.05). The spleen size between the lymphoma and inflammation patients was also significantly different (t = 2.911, P = 0.007 < 0.05).As indicated by F-FDG PET-CT, our study demonstrated that lymphoma and inflammation patients displayed a few differences despite both having high diffuse uptake of F-FDG in the spleen, liver, and bone marrow without enlarged peripheral lymph nodes and without increased F-FDG uptake in lymph nodes.