Microglial Activation Imaging Using 18F-DPA-714 PET/MRI for Detecting Autoimmune Encephalitis.

Background Translocator protein (TSPO) PET has been used to visualize microglial activation in neuroinflammation and is a potential imaging tool for detecting autoimmune encephalitis (AIE). Purpose To compare the detection rate between TSPO radioligand fluorine 18 (18F) DPA-714 PET and conventional MRI and assess the relationship between 18F-DPA-714 uptake and clinical features in participants with AIE. Materials and Methods Healthy volunteers and patients with AIE were enrolled in this prospective study between December 2021 and April 2023. All participants underwent hybrid brain 18F-DPA-714 PET/MRI and antibody testing. Modified Rankin scale scoring and AIE-related symptoms were assessed in participants with AIE. Positive findings were defined as intensity of 18F-DPA-714 uptake above a threshold of the mean standardized uptake value ratio (SUVR) plus 2 SD inside the corresponding brain regions of healthy controls. The McNemar test was used to compare the positive detection rate between the two imaging modalities; the independent samples t test was used to compare continuous variables; and correlation with Bonferroni correction was used to assess the relationship between 18F-DPA-714 uptake and clinical features. Results A total of 25 participants with AIE (mean age, 39.24 years ± 19.03 [SD]) and 10 healthy controls (mean age, 28.70 years ± 5.14) were included. The positive detection rate of AIE was 72% (18 of 25) using 18F-DPA-714 PET compared to 44% (11 of 25) using conventional MRI, but the difference was not statistically significant (P = .065). Participants experiencing seizures exhibited significantly higher mean SUVR in the entire cortical region than those without seizures (1.23 ± 0.21 vs 1.15 ± 0.18; P = .003). Of the 13 participants with AIE who underwent follow-up PET/MRI, 11 (85%) demonstrated reduced uptake of 18F-DPA-714 accompanied by relief of symptoms after immunosuppressive treatment. Conclusion 18F-DPA-714 PET has potential value in supplementing MRI for AIE detection. Clinical trial registration no. NCT05293405 © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Zaharchuk in this issue.

Topographic metabolism-function relationships in Alzheimer's disease: A simultaneous PET/MRI study.

Disruptions of neural metabolism and function occur in parallel during Alzheimer's disease (AD). While many studies have shown diverse metabolic-functional relationships in specific brain regions, much less is known about how large-scale network-level functional activity is associated with the topology of metabolism in AD. In this study, we took the advantages of simultaneous PET/MRI and multivariate analyses to investigate the associations between AD-related stereotypical spatial patterns (topographies) of glucose metabolism, measured by fluorodeoxyglucose PET, and functional connectivity, measured by resting-state functional MRI. A total of 101 participants, including 37 patients with AD, 25 patients with mild cognitive impairment (MCI), and 39 cognitively normal controls, underwent PET/MRI scans and cognitive assessments. Three pairs of distinct but optimally correlated metabolic and functional topographies were identified, encompassing large-scale networks including the default-mode, executive and control, salience, attention, and subcortical networks. Importantly, the metabolic-functional associations were not only limited to one-to-one-corresponding regions, but also occur in remote and non-overlapping regions. Furthermore, both glucose metabolism and functional connectivity, as well as their linkages, exhibited various degrees of disruptions in patients with MCI and AD, and were correlated with cognitive decline. In conclusion, our results support distributed and heterogeneous topographic associations between metabolism and function, which are jeopardized by AD. Findings of this study may deepen our understanding of the pathological mechanism of AD through the perspectives of both local energy efficiency and long-term interactions between synaptic disruption and functional disconnection contributing to the clinical symptomatology in AD.

Deep learning-based PET/MR radiomics for the classification of annualized relapse rate in multiple sclerosis.

Background Annualized Relapse Rate (ARR) is one of the most important indicators of disease progression in patients with Multiple Sclerosis (MS). However, imaging markers that can effectively predict ARR are currently unavailable. In this study, we developed a deep learning-based method for the automated extraction of radiomics features from Positron Emission Computed Tomography (PET) and Magnetic Resonance (MR) images to predict ARR in patients with MS. Methods Twenty-five patients with a definite diagnosis of Relapsing-Remitting MS (RRMS) were enrolled in this study. We designed a multi-branch fully convolutional neural network to segment lesions from PET/MR images. After that, radiomics features were extracted from the obtained lesion volume of interest. Three feature selection methods were used to retain features highly correlated with ARR. We combined four classifiers with different feature selection methods to form twelve models for ARR classification. Finally, the model with the best performance was chosen. Results Our network achieved precise automatic lesion segmentation with a Dice Similarity Coefficient (DSC) of 0.81 and a precision of 0.86. Radiomics features from lesions filtered by Recursive Feature Elimination (RFE) achieved the best performance in the Support Vector Machines (SVM) classifier. The classification model performance was best when radiomics from both PET and MR were combined to predict ARR, with high accuracy at 0.88 and Area Under the ROC curves (AUC) at 0.96, which outperformed MR or PET-based model and clinical indicators-based model. Conclusion Our automatic segmentation masks can replace manual ones with excellent performance. Furthermore, the deep learning and PET/MR radiomics-based model in our research is an effective tool in assisting ARR classification of MS patients.

A comparative study of [68Ga]Ga-FAPI-04 PET/MR and [18F]FDG PET/CT in the diagnostic accuracy and resectability prediction of ovarian cancer.

PURPOSE: To provide a theory for guiding clinical treatment by comparing the clinical application value of [18F]fluorodeoxyglucose ([18F]FDG) PET/CT and [68Ga]Ga-FAPI (fibroblast activating protein inhibitor) PET/MR in the diagnosis and evaluation of resectability of ovarian cancer. METHODS: Thirty patients with high clinical suspicion of ovarian malignancies were enrolled from July 2021 to October 2022 and underwent [18F]FDG PET/CT and [68Ga]Ga-FAPI-04 PET/MR within 5 days. Twenty patients underwent [18F]FDG PET/MR at once completing [18F]FDG PET/CT for consistency checking. Images were analysed for comparing SUVs and for judging incomplete resectability according to the peritoneal cancer index (PCI) and SUIDAN scoring system. The expression of FAP, HK2 and Ki67 was analysed by immunohistochemistry staining. RESULTS: There was no significant difference between PET/MR and PET/CT in SUVs-FDG at different locations (p > 0.05), and their diagnostic accuracies were similar. The diagnostic accuracy of [68Ga]Ga-FAPI-04 PET/MR had advantages for peritoneal metastasis since SUVsFAPI were higher (p < 0.01). The sensitivity of [68Ga]Ga-FAPI-04 PET/MR in the diagnosis of peridiaghragmatic metastases was higher because SUVmax in the liver was decreased (p < 0.001). [68Ga]Ga-FAPI-04 PET/MR might have advantages in diagnosing gastrointestinal invasion. In PCI score analysis, [68Ga]Ga-FAPI-04 PET/MR could partially correct missing or underestimated scores by [18F]FDG PET/CT, but the matching probability between left peri-intestinal metastasis scores was low and easy to overestimate. Interestingly, diaphragmatic metastasis detected by [68Ga]Ga-FAPI-04 PET/MR had the greatest correlation with the prediction of incomplete resectability (logistic regression p = 0.02). Through immunohistochemistry, the expression of FAP had a strong correlation with SUVmax-FAPI (p < 0.001), while the expression of HK2 was correlated with SUVmax-FDG (p < 0.01). In addition, SUVmax-FDG with Ki67 ≥ 20% was significantly higher than that with Ki67 < 20% (p < 0.05). CONCLUSIONS: [68Ga]Ga-FAPI-04 PET/MR had obvious advantages for metastases diagnosis and could more accurately assess tumour load and predict incomplete resectability. SUVmax-FDG was conducive to evaluating the degree of tumour malignancy.

The value of 18F-fluorodeoxyglucose positron emission tomography/magnetic resonance whole-body scans and local enhancement scans in the preoperative staging and resectability assessment of pancreatic adenocarcinoma.

Background: In addition to contrast-enhanced multiphase computed tomography (CT) and magnetic resonance imaging (MRI), integrated positron emission tomography (PET)/magnetic resonance (MR) is increasingly being used for the preoperative evaluation of pancreatic cancer. The purpose of this study was to explore the value of hybrid 18F-fluorodeoxyglucose (18F-FDG) PET/MR imaging in preoperative assessment and treatment decision-making. Methods: A retrospective data collection (of imaging, clinical, and pathological information) was conducted on patients who underwent 18F-FDG PET/MR with clinically diagnosed or suspected pancreatic cancer from March 2018 to March 2022 in Ruijin Hospital. The data of 76 patients were initially included, with 1 of the 76 patients eventually being excluded due to a misdiagnosis of inflammatory disease. Of the 75 patients, 38 underwent pancreatic tumor resection and 10 underwent laparoscopic exploration. The accuracy of 18F-FDG PET/MR for pancreatic cancer staging and the assessment of pancreatic resectability was evaluated based on pathological results, intraoperative findings, and documented final clinical stages of illness. The adjustments to patient treatment plans were also analyzed before and after 18F-FDG PET/MR examination. Results: The accuracy of clinical tumor node metastasis (TNM) staging of pancreatic cancer by 18F-FDG PET/MR was 73.3% (55/75). The area under the curve (AUC) of 18F-FDG PET/MR for diagnosing the advanced stage (III-IV) versus the nonadvanced stage (I-II) of disease was 0.922 [95% confidence interval (CI): 0.852-0.993]. The treatment regimen of 20.0% (15/75) of patients was impacted. The accuracy of the evaluation of the resectability of pancreatic cancer with 18F-FDG PET/MR was 91.9% (34/37). With the surgical and pathological results being used as a reference, the overall accuracy of preoperative 18F-FDG PET/MR for T staging was 62.2%, and the AUC for diagnosing T4 versus T1-3 was 0.872 (95% CI: 0.660-1.000). Conclusions: 18F-FDG PET/MR performs well in diagnosing advanced pancreatic cancer and thus may impact the treatment decisions for a considerable number of patients. 18F-FDG PET/MR has a high level of accuracy in evaluating the resectability of pancreatic cancer before surgery.

[68Ga]Ga-DOTA-FAPI-04 PET/MR in patients with acute myocardial infarction: potential role of predicting left ventricular remodeling.

PURPOSE: To assess predictive value of 68Ga-labeled fibroblast activation protein inhibitor-04 ([68Ga]Ga-DOTA-FAPI-04) PET/MR for late left ventricular (LV) remodeling in patients with ST-segment elevated myocardial infarction (STEMI). METHODS: Twenty-six patients with STEMI were included in the study. [68Ga]Ga-DOTA-FAPI-04 PET/MR was performed at baseline and at average 12 months after STEMI. LV remodeling was defined as >10% increase in LV end-systolic volume (LVESV) from baseline to 12 months. RESULTS: The LV remodeling group demonstrated higher [68Ga]Ga-DOTA-FAPI-04 uptake volume (UV) at baseline than the non-LV remodeling group (p < 0.001). [68Ga]Ga-DOTA-FAPI-04 UV at baseline was a significant predictor (OR = 1.048, p = 0.011) for LV remodeling at 12 months after STEMI. Compared to clinical information, MR imaging and cardiac function parameters at baseline, [68Ga]Ga-DOTA-FAPI-04 UV demonstrated better predictive ability (AUC = 0.938, p < 0.001) for late LV remodeling, with sensitivity of 100.0% and specificity of 81.3%. CONCLUSIONS: [68Ga]Ga-DOTA-FAPI-04 PET/MR is an effective tool to non-invasively quantify myocardial fibroblasts activation, and baseline [68Ga]Ga-DOTA-FAPI-04 UV may have potential predictive value for late LV remodeling.

Characteristics of cerebral blood flow in an Eastern sample of multiple sclerosis patients: A potential quantitative imaging marker associated with disease severity.

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system that is rare in China. At present, there are no widespread quantitative imaging markers associated with disease severity in MS. Despite several previous studies reporting cerebral blood flow (CBF) changes in MS, no consensus has been reached. In this study, we enrolled 30 Eastern MS patients to investigate CBF changes in different brain regions using the arterial spin labeling technique and their relationship with disease severity. The average CBF in MS patients were higher than those in health controls in various brain regions except cerebellum. The results indicated that MS patients with strongly increased CBF showed worse disease severity, including higher Expanded Disability Status Scale (EDSS) scores and serum neurofilament light chain (sNfL) values than those with mildly increased CBF in the parietal lobes, temporal lobes, basal ganglia, and damaged white matter (DWM). From another perspective, MS patients with worse disease severity (higher EDSS score and sNfL values, longer disease duration) showed increased CBF in parietal lobes, temporal lobes, basal ganglia, normal-appearing white matter (NAWM), and DWM. Correlation analysis showed that there was a strong association among CBF, EDSS score and sNfL. MS patients with strongly increased CBF in various brain regions had more ratio in relapsing phase than patients with mildly increased CBF. And relapsing patients showed significantly higher CBF in some regions (temporal lobes, left basal ganglia, right NAWM) compared to remitting patients. In addition, MS patients with cognitive impairment had higher CBF than those without cognitive impairment in the right parietal lobe and NAWM. However, there were no significant differences in CBF between MS patients with and without other neurologic dysfunctions (e.g., motor impairment, visual disturbance, sensory dysfunction). These findings expand our understanding of CBF in MS and imply that CBF could be a potential quantitative imaging marker associated with disease severity.

Aerobic glycolysis imaging of epileptic foci during the inter-ictal period.

BACKGROUND: In drug-resistant epilepsy, surgical resection of the epileptic focus can end seizures. However, success is dependent on the ability to identify foci locations and, unfortunately, current methods like electrophysiology and positron emission tomography can give contradictory results. During seizures, glucose is metabolized at epileptic foci through aerobic glycolysis, which can be imaged through the oxygen-glucose index (OGI) biomarker. However, inter-ictal (between seizures) OGI changes have not been studied, which has limited its application. METHODS: 18 healthy controls and 24 inter-ictal, temporal lobe epilepsy patients underwent simultaneous positron emission tomography (PET) and magnetic resonance imaging (MRI) scans. We used [18F]fluorodeoxyglucose-PET (FDG-PET) to detect cerebral glucose metabolism, and calibrated functional MRI to acquire relative oxygen consumption. With these data, we calculated relative OGI maps. FINDINGS: While bilaterally symmetrical in healthy controls, we observed, in patients during the inter-ictal period, higher OGI ipsilateral to the epileptic focus than contralateral. While traditional FDG-PET results and temporal lobe OGI results usually both agreed with invasive electrophysiology, in cases where FDG-PET disagreed with electrophysiology, temporal lobe OGI agreed with electrophysiology, and vice-versa. INTERPRETATION: As either our novel epilepsy biomarker or traditional approaches located foci in every case, our work provides promising insights into metabolic changes in epilepsy. Our method allows single-session OGI measurement which can be useful in other diseases. FUNDING: This work was supported by ShanghaiTech University, the Shanghai Municipal Government, the National Natural Science Foundation of China Grant (No. 81950410637) and Shanghai Municipal Key Clinical Specialty (No. shslczdzk03403). F. H. and P. H. were supported by USA National Institute of Health grants (R01 NS-100106, R01 MH-067528).Z. W. was supported by the Key-Area Research and Development Program of Guangdong Province (2019B030335001), National Natural Science Foundation of China (No. 82151303), and National Key R&D Program of China (No. 2021ZD0204002).

Disrupted coupling between salience network segregation and glucose metabolism is associated with cognitive decline in Alzheimer's disease - A simultaneous resting-state FDG-PET/fMRI study.

The aberrant organization and functioning of three core neurocognitive networks (NCNs), i.e., default-mode network (DMN), central executive network (CEN), and salience network (SN), are among the prominent features in Alzheimer's disease (AD). The dysregulation of both intra- and inter-network functional connectivities (FCs) of the three NCNs contributed to AD-related cognitive and behavioral abnormalities. Brain functional network segregation, integrating intra- and inter-network FCs, is essential for maintaining the energetic efficiency of brain metabolism. The association of brain functional network segregation, together with glucose metabolism, with age-related cognitive decline was recently shown. Yet how these joint functional-metabolic biomarkers relate to cognitive decline along with mild cognitive impairment (MCI) and AD remains to be elucidated. In this study, under the framework of the triple-network model, we performed a hybrid FDG-PET/fMRI study to evaluate the concurrent changes of resting-state brain intrinsic FCs and glucose metabolism of the three NCNs across cognitively normal (CN) (N = 24), MCI (N = 21), and AD (N = 21) groups. Lower network segregation and glucose metabolism were observed in all three NCNs in patients with AD. More interestingly, in the SN, the coupled relationship between network segregation and glucose metabolism existed in the CN group (r = 0.523, p = 0.013) and diminished in patients with MCI (r = 0.431, p = 0.065) and AD (r = 0.079, p = 0.748). Finally, the glucose metabolism of the DMN (r = 0.380, p = 0.017) and the network segregation of the SN (r = 0.363, p = 0.023) were significantly correlated with the general cognitive status of the patients. Our findings suggest that the impaired SN segregation and its uncoupled relationship with glucose metabolism contribute to the cognitive decline in AD.

Combined quantitative T2 mapping and [18F]FDG PET could improve lateralization of mesial temporal lobe epilepsy.

OBJECTIVES: To investigate whether quantitative T2 mapping is complementary to [18F]FDG PET in epileptogenic zone detection, thus improving the lateralization accuracy for drug-resistant mesial temporal lobe epilepsy (MTLE) using hybrid PET/MR. METHODS: We acquired routine structural MRI, T2-weighted FLAIR, whole brain T2 mapping, and [18F]FDG PET in 46 MTLE patients and healthy controls on a hybrid PET/MR scanner, followed with computing voxel-based z-score maps of patients in reference to healthy controls. Asymmetry indexes of the hippocampus were calculated for each imaging modality, which then enter logistic regression models as univariate or multivariate for lateralization. Stereoelectroencephalography (SEEG) recordings and clinical decisions were collected as gold standard. RESULTS: Routine structural MRI and T2w-FLAIR lateralized 47.8% (22/46) of MTLE patients, and FDG PET lateralized 84.8% (39/46). T2 mapping combined with [18F]FDG PET improved the lateralization accuracy by correctly lateralizing 95.6% (44/46) of MTLE patients. The asymmetry indexes of hippocampal T2 relaxometry and PET exhibit complementary tendency in detecting individual laterality, especially for MR-negative patients. In the quantitative analysis of z-score maps, the ipsilateral hippocampus had significantly lower SUVR (LTLE, p < 0.001; RTLE, p < 0.001) and higher T2 value (LTLE, p < 0.001; RTLE, p = 0.001) compared to the contralateral hippocampus. In logistic regression models, PET/T2 combination resulted in the highest AUC of 0.943 in predicting lateralization for MR-negative patients, followed by PET (AUC = 0.857) and T2 (AUC = 0.843). CONCLUSIONS: The combination of quantitative T2 mapping and [18F]FDG PET could improve lateralization for temporal lobe epilepsy. KEY POINTS: • Quantitative T2 mapping and18F-FDG PET are complementary in the characterization of hippocampal alterations of MR-negative temporal lobe epilepsy patients. • The combination of quantitative T2 and18F-FDG PET obtained from hybrid PET/MR could improve lateralization for temporal lobe epilepsy.

A cross-scanner and cross-tracer deep learning method for the recovery of standard-dose imaging quality from low-dose PET.

PURPOSE: A critical bottleneck for the credibility of artificial intelligence (AI) is replicating the results in the diversity of clinical practice. We aimed to develop an AI that can be independently applied to recover high-quality imaging from low-dose scans on different scanners and tracers. METHODS: Brain [18F]FDG PET imaging of 237 patients scanned with one scanner was used for the development of AI technology. The developed algorithm was then tested on [18F]FDG PET images of 45 patients scanned with three different scanners, [18F]FET PET images of 18 patients scanned with two different scanners, as well as [18F]Florbetapir images of 10 patients. A conditional generative adversarial network (GAN) was customized for cross-scanner and cross-tracer optimization. Three nuclear medicine physicians independently assessed the utility of the results in a clinical setting. RESULTS: The improvement achieved by AI recovery significantly correlated with the baseline image quality indicated by structural similarity index measurement (SSIM) (r = -0.71, p < 0.05) and normalized dose acquisition (r = -0.60, p < 0.05). Our cross-scanner and cross-tracer AI methodology showed utility based on both physical and clinical image assessment (p < 0.05). CONCLUSION: The deep learning development for extensible application on unknown scanners and tracers may improve the trustworthiness and clinical acceptability of AI-based dose reduction.

Simultaneous PET/fMRI Detects Distinctive Alterations in Functional Connectivity and Glucose Metabolism of Precuneus Subregions in Alzheimer's Disease.

As a central hub in the interconnected brain network, the precuneus has been reported showing disrupted functional connectivity and hypometabolism in Alzheimer's disease (AD). However, as a highly heterogeneous cortical structure, little is known whether individual subregion of the precuneus is uniformly or differentially involved in the progression of AD. To this end, using a hybrid PET/fMRI technique, we compared resting-state functional connectivity strength (FCS) and glucose metabolism in dorsal anterior (DA_pcu), dorsal posterior (DP_pcu) and ventral (V_pcu) subregions of the precuneus among 20 AD patients, 23 mild cognitive impairment (MCI) patients, and 27 matched cognitively normal (CN) subjects. The sub-parcellation of precuneus was performed using a K-means clustering algorithm based on its intra-regional functional connectivity. For the whole precuneus, decreased FCS (p = 0.047) and glucose hypometabolism (p = 0.006) were observed in AD patients compared to CN subjects. For the subregions of the precuneus, decreased FCS was found in DP_pcu of AD patients compared to MCI patients (p = 0.011) and in V_pcu for both MCI (p = 0.006) and AD (p = 0.008) patients compared to CN subjects. Reduced glucose metabolism was found in DP_pcu of AD patients compared to CN subjects (p = 0.038) and in V_pcu of AD patients compared to both MCI patients (p = 0.045) and CN subjects (p < 0.001). For both FCS and glucose metabolism, DA_pcu remained relatively unaffected by AD. Moreover, only in V_pcu, disruptions in FCS (r = 0.498, p = 0.042) and hypometabolism (r = 0.566, p = 0.018) were significantly correlated with the cognitive decline of AD patients. Our results demonstrated a distinctively disrupted functional and metabolic pattern from ventral to dorsal precuneus affected by AD, with V_pcu and DA_pcu being the most vulnerable and conservative subregion, respectively. Findings of this study extend our knowledge on the differential roles of precuneus subregions in AD.

Amyloid-Beta Influences Memory via Functional Connectivity During Memory Retrieval in Alzheimer's Disease.

Objective: Amnesia in Alzheimer's disease (AD) appears early and could be caused by encoding deficiency, consolidation dysfunction, and/or impairment in the retrieval of stored memory information. The relationship between AD pathology biomarker ß-amyloid and memory dysfunction is unclear. Method: The memory task functional MRI and amyloid PET were simultaneously performed to investigate the relationship between memory performance, memory phase-related functional connectivity, and cortical ß-amyloid deposition. We clustered functional networks during memory maintenance and compared network connectivity between groups in each memory phase. Mediation analysis was performed to investigate the mediator between ß-amyloid and related cognitive performance. Results: Alzheimer's disease was primarily characterized by decreased functional connectivity in a data-driven network composed of an a priori default mode network, limbic network, and frontoparietal network during the memory maintenance (0.205 vs. 0.236, p = 0.04) and retrieval phase (0.159 vs. 0.183, p = 0.017). Within the network, AD had more regions with reduced connectivity during the retrieval than the maintenance and encoding phases (chi-square p = 0.01 and < 0.001). Furthermore, the global cortical ß-amyloid negatively correlated with network connectivity during the memory retrieval phase (R = - 0.247, p = 0.032), with this relationship mediating the effect of cortical ß-amyloid on memory performance (average causal mediation effect = - 0.05, p = 0.035). Conclusion: We demonstrated that AD had decreased connectivity in specific networks during the memory retrieval phase. Impaired functional connectivity during memory retrieval mediated the adverse effect of ß-amyloid on memory. These findings help to elucidate the involvement of cortical ß-amyloid (Aß) in the memory performance in the early stages of AD.

18F-florbetapir PET/MRI for quantitatively monitoring myelin loss and recovery in patients with multiple sclerosis: A longitudinal study.

BACKGROUND: Amyloid positron emission tomography (PET) can measure in-vivo demyelination in patients with multiple sclerosis (MS). However, the value of 18F-labeled amyloid PET tracer, 18F-florbetapir in the longitudinal study for monitoring myelin loss and recovery has not been confirmed. METHODS: From March 2019 to September 2020, twenty-three patients with MS and nine healthy controls (HCs) underwent a hybrid PET/MRI at baseline and expanded disability status scale (EDSS) assessment, and eight of 23 patients further underwent follow-up PET/MRI. The distribution volume ratio (DVR) and standard uptake value ratio (SUVR) of 18F-florbetapir in damaged white matter (DWM) and normal-appearance white matter (NAWM) were obtained from dynamic and static PET acquisition. Diffusion tensor imaging-derived parameters were also calculated. Data were expressed as mean ± standard deviation with 99% confidence interval (99%CI). FINDING: The mean DVR (1.08 ± 0.12, 99%CI [1.02 ~ 1.14]) but not the mean SUVR of DWM lesions was lower than that of NAWM in patients with MS (1.25 ± 0.10, 99%CI [1.20 ~ 1.31]) and HCs (1.29 ± 0.08, 99%CI [1.23 ~ 1.36]). A trend toward lower mean fractional anisotropy (374.95 ± 45.30 vs. 419.07 ± 4.83) and higher mean radial diffusivity (0.45 ± 0.05 vs. 0.40 ± 0.01) of NAWM in patients with MS than those in HCs was found. DVR decreased in DWM lesions with higher MD (rho = -0.261, 99%CI [-0.362 ~ -0.144]), higher AD (rho = -0.200, 99%CI [-0.318 ~ -0.070]) and higher RD (rho = -0.198, 99%CI [-0.313 ~ -0.075]). Patients' EDSS scores were reduced (B = 0.04, 99%CI [-0.005 ~ 0.084]) with decreased index of global demyelination in the longitudinal study. INTERPRETATION: Our exploratory study suggests that dynamic 18F-florbetapir PET/MRI may be a very promising tool for quantitatively monitoring myelin loss and recovery in patients with MS. FUNDING: Shanghai Pujiang Program, Shanghai Municipal Key Clinical Specialty, Shanghai Shuguang Plan Project, Shanghai Health and Family Planning Commission Research Project, Clinical Research Plan of SHDC, French-Chinese program "Xu Guangqi".

Performance of 18F-FDG PET/CT Radiomics for Predicting EGFR Mutation Status in Patients With Non-Small Cell Lung Cancer.

OBJECTIVE: To assess the performance of pretreatment 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) radiomics features for predicting EGFR mutation status in patients with non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: We enrolled total 173 patients with histologically proven NSCLC who underwent preoperative 18F-FDG PET/CT. Tumor tissues of all patients were tested for EGFR mutation status. A PET/CT radiomics prediction model was established through multi-step feature selection. The predictive performances of radiomics model, clinical features and conventional PET-derived semi-quantitative parameters were compared using receiver operating curves (ROCs) analysis. RESULTS: Four CT and two PET radiomics features were finally selected to build the PET/CT radiomics model. Compared with area under the ROC curve (AUC) equal to 0.664, 0.683 and 0.662 for clinical features, maximum standardized uptake values (SUVmax) and total lesion glycolysis (TLG), the PET/CT radiomics model showed better performance to discriminate between EGFR positive and negative mutations with the AUC of 0.769 and the accuracy of 67.06% after 10-fold cross-validation. The combined model, based on the PET/CT radiomics and clinical feature (gender) further improved the AUC to 0.827 and the accuracy to 75.29%. Only one PET radiomics feature demonstrated significant but low predictive ability (AUC = 0.661) for differentiating 19 Del from 21 L858R mutation subtypes. CONCLUSIONS: EGFR mutations status in patients with NSCLC could be well predicted by the combined model based on 18F-FDG PET/CT radiomics and clinical feature, providing an alternative useful method for the selection of targeted therapy.

Utility of hybrid PET/MRI multiparametric imaging in navigating SEEG placement in refractory epilepsy.

PURPOSE: Stereo-electroencephalography (SEEG) implantation before epilepsy surgery is critical for precise localization and complete resection of the seizure onset zone (SOZ). Combined metabolic and morphological imaging using hybrid PET/MRI may provide supportive information for the optimization of the SEEG coverage of brain structures. In this study, we originally imported PET/MRI images into the SEEG positioning system to evaluate the application of PET/MRI in guiding SEEG implantation in refractory epilepsy patients. MATERIALS: Forty-two patients undergoing simultaneous PET/MRI examinations were recruited. All the patients underwent SEEG implantation guided by hybrid PET/MRI and surgical resection or ablation of epileptic lesion. Surgery outcome was assessed using a modified Engel classification one year (13.60 ± 2.49 months) after surgery. Areas of SOZ were identified using hybrid PET/MRI and concordance with SEEG was evaluated. Logistic regression analysis was used to predict the presence of a favorable outcome with the coherence of concordance of PET/MRI and SEEG. RESULTS: Hybrid PET/MRI (including visual PET, MRI, plus MI Neuro) identified SOZ lesions in 38 epilepsy patients (90.47 %). PET/MRI showed the same SOZ localization with SEEG in 29 patients (69.05 %), which was considered to be concordant. The concordance between the PET/MRI and SEEG findings was significantly predictive of a successful surgery outcome (odds ratio = 20.41; 95 % CI = 2.75-151.4, P = 0.003**). CONCLUSION: Hybrid PET/MRI combined visual PET, multiple sequences MRI and SPM PET helps identify epilepsy lesions particularly in subtle hypometabolic areas. Patients with concordant epileptic lesion localization on PET/MRI and SEEG demonstrated a more favorable outcome than those with inconsistent localization between modalities.

Performance of Multiparametric Functional Imaging and Texture Analysis in Predicting Synchronous Metastatic Disease in Pancreatic Ductal Adenocarcinoma Patients by Hybrid PET/MR: Initial Experience.

Objectives: To assess the imaging biomarkers of glucose metabolic activity and diffusion-weighted imaging (DWI) derived from pretreatment integrated 18F-fluorodeoxyglucose positron emission tomography-magnetic resonance (18F-FDG PET/MR) imaging as potential predictive factors of metastasis in patients with pancreatic ductal adenocarcinoma (PDAC). Patients and Methods: We retrospectively included 17 consecutive patients with pathologically confirmed PDAC by pretreatment 18F-FDG PET/MR. The study subjects were divided into a non-metastatic group (M0, six cases) and a metastatic group (M1, 11 cases). The 18F-FDG PET/MR images were reviewed independently by two board certificated nuclear medicine physicians and one radiologist. Conventional characteristics and quantitative parameters from both PET and apparent diffusion coefficient (ADC) were assessed. The texture features were extracted from LIFEx packages (www.lifexsoft.org), and a 3D tumor volume of interest was manually drawn on fused PET/ADC images. Chi-square tests, independent-samples t-tests and Mann-Whitney U-tests were used to compare the differences in single parameters between the two groups. A logistic regression analysis was performed to determine independent predictors. A receiver operating characteristic (ROC) curve analysis was performed to assess the discriminatory power of the selected parameters. Correlations between metabolic parameters and ADC features were calculated with Spearman's rank correlation coefficient test. Results: For conventional parameters, univariable analysis demonstrated that the M1 group had a significantly larger size and a higher peak of standardized uptake value (SUVpeak), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) than those of the M0 group (p < 0.05 for all). TLG remained significant predictor in the multivariable analysis, but there were no significant differences for the area under the ROC curve (AUC) among the four conventional features in differential diagnoses (p > 0.05 for all). For the texture features, there were four features from the PET image and 13 from the ADC map that showed significant differences between the two groups. Multivariate analysis indicated that one feature from PET and three from the ADC were significant predictors. TLG was associated with ADC-GLRLM_GLNU (r = 0.659), ADC-GLRLM_LRHGE (r = 0.762), and PET-GLRLM_LRHGE (r = 0.806). Conclusions: Multiple parameters and texture features of primary tumors from 18F-FDG PET/MR images maybe reliable biomarkers to predict synchronous metastatic disease for the pretreatment PDAC.

Semi-quantitative analysis of 99mTc-sestamibi retention level for preoperative differential diagnosis of parathyroid carcinoma.

BACKGROUND: To investigate the role of 99mTc-labeled sestamibi (99mTc-MIBI) retention level in the assessment of malignant potential of parathyroid lesions. METHODS: Twenty patients with parathyroid carcinomas and forty controls with benign parathyroid lesions who underwent preoperatively 99mTc-MIBI dual-phase planar and SPECT/CT imaging were retrospectively enrolled in this study. The mean and peak of retention index (RImean and RIpeak) were measured for evaluating the retention level of 99mTc-MIBI in the parathyroid lesions. Diagnostic accuracies of RI for differentiating malignant parathyroid lesions from benign ones were assessed by receiver operating characteristic analyses (area under the curve; AUC). RESULTS: RIpeak (AUC =0.87, P<0.001) and RImean (AUC =0.78, P<0.001) showed significant difference between the malignant and benign lesions. The diagnostic sensitivity, specificity, positive and negative predictive values, accuracy of RIpeak were respectively 80.0%, 85.0%, 72.7%, 89.5% and 83.3% when its cutoff value was -19.03%. In addition, the level of serum parathyroid hormone (PTH) slightly correlated with RIpeak (r=0.260, P=0.044) or RImean (r=0.281, P=0.029). CONCLUSIONS: Parathyroid carcinomas have higher retention level of 99mTc-MIBI than benign parathyroid lesions. RIpeak may contribute to preoperative differential diagnosis of parathyroid carcinoma.

Value of 99mTc-MIBI SPECT/CT parathyroid imaging and ultrasonography for concomitant thyroid carcinoma.

PURPOSE: We aimed to assess the frequency of carcinoma in cases with suspected parathyroid adenoma and test the value of Tc-methoxyisobutylisonitrile (Tc-MIBI) single-photon emission computed tomography/computed tomography (SPECT/CT) parathyroid imaging and neck ultrasonography in detecting concomitant thyroid carcinoma. PATIENTS AND METHODS: We enrolled 741 patients with clinically suspected parathyroid adenoma who underwent Tc-MIBI planer scans and SPECT/CT of the skull base, neck, and thorax; patients also underwent ultrasonography within 1 month before SPECT/CT. Each case with suspected lesion was analyzed and correlated with pathology. We estimated the frequency of carcinoma detection on SPECT/CT performed for suspected parathyroid adenoma. The sensitivity, specificity, and accuracy of detecting thyroid carcinoma were estimated for both SPECT/CT and ultrasonography. RESULTS: In total, 222 patients with 250 pathology results were assessed. Of these, 54 patients showed carcinoma. With respect to the anatomical distribution of the incidental findings, 19 (35.19%) had parathyroid carcinoma, 20 (37.04%) had papillary thyroid carcinoma, three (5.56%) had follicular thyroid carcinoma, six (11.11%) had medullary thyroid carcinoma, and six (11.11%) had other carcinomas. For thyroid carcinoma detection, the sensitivity, specificity, and accuracy were 35.71, 88.16, and 80.49% for SPECT/CT and 73.81, 95.10, and 91.99% for ultrasonography, respectively. CONCLUSION: The frequency of carcinoma is high on Tc-MIBI SPECT/CT performed for suspected parathyroid adenoma. Although Tc-MIBI SPECT/CT plays an important role in the diagnosis and location of parathyroid adenoma, ultrasonography appears to be more suitable for identifying a concomitant thyroid carcinoma. This may vitally influence the choice of therapeutic regimen in patients with primary hyperparathyroidism.

Increases in the risk of cognitive impairment and alterations of cerebral ß-amyloid metabolism in mouse model of heart failure.

Epidemiological and clinico-pathological studies indicate a causal relationship between heart disease and Alzheimer's disease (AD). To learn whether heart disease causes an onset of AD, mice with myocardial infarction (MI) and congestive heart failure (HF) were used to test neuropsychiatric and cognitive behaviors as well as for measurements of AD related protein markers. To this end, adult mice were subjected to ligation of left anterior descending artery (LAD) and about two weeks later high-frequency echocardiography was performed to exam the resulting cardiac structure and function. Three months after successful induction of chronic heart failure (CHF) these mice showed an impairment of learning in the Morris Water Maze task. In addition, the expression of selected molecules, which are involved in ß-amyloid metabolism, apoptosis and inflammation on the level of gene transcription and translation, was altered in CHF mice. Our findings provide a plausible explanation that CHF increases the risk of cognitive impairments and alters cerebral ß-amyloid metabolism. In addition, our data indicate that the cerebral compensatory mechanisms in response to CHF are brain area and gender specific.