Exploring the association of glioma tumor residuals from incongruent [18F]FET PET/MR imaging with tumor proliferation using a multiparametric MRI radiomics nomogram.

PURPOSE: The study aimed to using multiparametric MRI radiomics to predict glioma tumor residuals (TRFET over MR) derived from incongruent [18F]fluoroethyl-L-tyrosine ([18F]FET) PET/MR imaging. METHODS: One hundred ten patients with gliomas who underwent [18F]FET PET/MR scanning were retrospectively analyzed. The TRFET over MR was identified by the discrepancy-PET that the extent of resection (EOR) based on MRI subtracted the biological tumor volume on PET images. The MRI parameters and radiomics features were extracted based on EOR and selected by the least absolute shrinkage and selection operator to construct radiomics score (Rad-score). The correlation network analysis of all features was analyzed by Spearman's correlation tests. The methods for evaluating the clinical usefulness consisted of the receiver operating characteristic curve, the calibration curve, and decision curve analysis. RESULTS: The Rad-score of the patients with the TRFET over MR was significantly higher than those with the non TRFET over MR (p < 0.001). The Rad-score was significantly correlated with the discrepancy-PET (r = 0.72, p < 0.001), Ki-67 level (r = 0.76, p < 0.001), and epidermal growth factor receptor (EGFR) of gliomas (r = 0.75, p < 0.001), respectively. Moreover, there was a difference of the correlation network analysis between the TRPET over MR group and non TRFET over MR group. The nomogram combing Rad-score and clinical features had the greatest performance in predicting TRFET over MR (AUC = 0.90/0.87, training/testing). There was a significant difference in prognosis (median OS, 17 m vs. 43 m) between patients with TRFET over MR and non TRFET over MR based on nomogram prediction (p < 0.001). CONCLUSION: The nomogram based on MRI radiomics would predict gliomas tumor residuals caused by the absence of 18F-PET PET examination and adjust EOR to improve prognosis.

Comparison of the diagnostic value of [68 Ga]Ga-FAPI-04 PET/MR and [18F]FDG PET/CT in patients with T stage ≤ 2a2 uterine cervical cancer: a prospective study.

PURPOSE: To compare the diagnostic value of [68 Ga]Ga-FAPI-04 PET/MR and [18F]FDG PET/CT in patients with T stage ≤ 2a2 uterine cervical cancer patients. METHODS: Patients pathologically diagnosed with cervical cancer and with a T stage ≤ T2a2 were prospectively enrolled. All patients underwent whole-body [68 Ga]Ga-FAPI-04 PET/MR and [18F]FDG PET/CT within 2 weeks, and surgical treatment was performed within 10 days after PET. RESULTS: Twenty-five patients were enrolled. Twenty patients underwent radical hysterectomy, among which all of them underwent pelvic lymphadenectomy, and 10 patients underwent para-aortic lymphadenectomy. Three patients received merely laparoscopic lymphadenectomy without hysterectomy. Two patients with both [18F]FDG and [68 Ga]Ga-FAPI-04 lymph node high metabolism were staged as FIGO IIIC1r, and concurrent chemoradiation therapy (CCRT) was performed. [18F]FDG and [68 Ga]Ga-FAPI-04 had equivalent detection ability on primary tumors, with a positive detection rate of 96.0%. The accuracy of T staging using [18F]FDG and [68 Ga]Ga-FAPI-04 was relatively 50% and 55.0%. Elevated and underrated staging was due to misdiagnosis of either vaginal infiltration or tumor size. In terms of lymph node metastasis detection, the specificity of [68 Ga]Ga-FAPI-04 was 100% (95% CI, 84.6% ~ 100.0%), which was significantly higher than [18F]FDG (59.1% (95% CI, 36.4% ~ 79.3%)) (p = 0.004). CONCLUSION: [68 Ga]Ga-FAPI-04 PET/MR and [18F]FDG PET/CT demonstrated an equivalent detection ability on cervical cancer primary tumors. However, [68 Ga]Ga-FAPI-04 PET/MR's diagnostic value in lymph node metastasis was significantly higher than [18F]FDG PET/CT. [68 Ga]Ga-FAPI-04 PET/MR has the potential for more accurate treatment planning, thus clarifying fertility preservation indications for early-stage young patients.

Integrating TSPO PET imaging and transcriptomics to unveil the role of neuroinflammation and amyloid-ß deposition in Alzheimer's disease.

PURPOSE: Despite the revealed role of immunological dysfunctions in the development and progression of Alzheimer's disease (AD) through animal and postmortem investigations, direct evidence regarding the impact of genetic factors on microglia response and amyloid-ß (Aß) deposition in AD individuals is lacking. This study aims to elucidate this mechanism by integrating transcriptomics and TSPO, Aß PET imaging in clinical AD cohort. METHODS: We analyzed 85 patients with PET/MR imaging for microglial activation (TSPO, [18F]DPA-714) and Aß ([18F]AV-45) within the prospective Alzheimer's Disease Immunization and Microbiota Initiative Study Cohort (ADIMIC). Immune-related differentially expressed genes (IREDGs), identified based on AlzData, were screened and verified using blood samples from ADIMIC. Correlation and mediation analyses were applied to investigate the relationships between immune-related genes expression, TSPO and Aß PET imaging. RESULTS: TSPO uptake increased significantly both in aMCI (P < 0.05) and AD participants (P < 0.01) and showed a positive correlation with Aß deposition (r = 0.42, P < 0.001). Decreased expression of TGFBR3, FABP3, CXCR4 and CD200 was observed in AD group. CD200 expression was significantly negatively associated with TSPO PET uptake (r =-0.33, P = 0.013). Mediation analysis indicated that CD200 acted as a significant mediator between TSPO uptake and Aß deposition (total effect B = 1.92, P = 0.004) and MMSE score (total effect B =-54.01, P = 0.003). CONCLUSION: By integrating transcriptomics and TSPO PET imaging in the same clinical AD cohort, this study revealed CD200 played an important role in regulating neuroinflammation, Aß deposition and cognitive dysfunction.

[68Ga]Ga-FAPI-04 PET/MR imaging strategy in management of Krukenberg tumors (KTs) from gastric signet-ring-cell carcinoma: to overcome limitation of [68Ga]Ga-FAPI-04 PET imaging in KTs.

PURPOSE: To compare performance of whole-body [68Ga]Ga-FAPI-04 and [18F]FDG PET imaging in the detection of Krukenberg tumors (KTs), primary site and extra-ovarian metastases of gastric signet-ring-cell carcinoma (GSRCC), and evaluate the value of [68Ga]Ga-FAPI-04 PET/MR imaging strategy and its potential impact on the management of KTs from GSRCC. METHODS: Twelve patients with twenty-three KTs from GSRCC, who underwent both [68Ga]Ga-FAPI-04 pelvic PET/MR and whole-body [68Ga]Ga-FAPI-04 and [18F]FDG PET imaging were retrospectively analyzed. [68Ga]Ga-FAPI-04 and [18F]FDG uptakes were compared by using Wilcoxon signed-rank test or paired t test. McNemar's test was used to compare lesion detectability between two modalities. Two-tailed P<0.05 was considered statistically significant. Immunohistochemistry staining was utilized to analyze the fibroblast activation protein (FAP) expression in KTs. RESULTS: A total of 12 patients with 23 KTs from GSRCC (8 synchronous and 4 metachronous) were evaluated. [68Ga]Ga-FAPI-04 was superior to [18F]FDG PET in detecting primary sites of GSRCC (100% [11/11] vs. 18.2% [2/11], p = 0.002), involved lymph nodes (90.9% [10/11] vs. 54.5% [6/11], p = 0.046) and peritoneal metastases (100% [12/12] vs. 41.7% [5/12], p = 0.008), with higher SUVmax and TBR (all p < 0.005). Both tracers had limited value in identifying KTs, with 100% false negative rate on [68Ga]Ga-FAPI-04 PET and a low detection rate of 8.7% on [18F]FDG PET. Fap immunohistochemistry showed negative or slight FAP expression in neoplastic signet ring cells and ovarian stroma. [68Ga]Ga-FAPI-04 PET/MR imaging strategy greatly improved the detection rate of Krukenberg tumors (87%, 20/23). After adding diffusion-weighted imaging (DWI), the detection rate was further improved (87.5% vs. 100%, p = 0.083). [68Ga]Ga-FAPI-04 PET/MR imaging strategy either upgraded TNM staging or changed treatment management in twelve patients. CONCLUSIONS: [68Ga]Ga-FAPI-04 PET outperformed [18F]FDG PET in detecting primary site and most extra-ovarian metastases of GSRCC, but both tracers had limited value in identifying Krukenberg tumors. Pelvis MRI should be applied to compensate the limitation of [68Ga]Ga-FAPI-04 PET imaging to identify Krukenberg tumours. The [68Ga]Ga-FAPI-04 PET/MR imaging strategy has the potential to impact treatment decisions for GSRCC patients with KTs.

Tri-Compartmental Restriction Spectrum Imaging Based on 18F-FDG PET/MR for Identification of Primary Benign and Malignant Lung Lesions.

BACKGROUND: Restriction spectrum imaging (RSI), as an advanced quantitative diffusion-weighted magnetic resonance imaging technique, has the potential to distinguish primary benign and malignant lung lesions. OBJECTIVE: To explore how well the tri-compartmental RSI performs in distinguishing primary benign from malignant lung lesions compared with diffusion-weighted imaging (DWI), and to further explore whether positron emission tomography/magnetic resonance imaging (PET/MRI) can improve diagnostic efficacy. STUDY TYPE: Prospective. POPULATION: 137 patients, including 108 malignant and 29 benign lesions (85 males, 52 females; average age = 60.0 ± 10.0 years). FIELD STRENGTH/SEQUENCE: T2WI, T1WI, multi-b value DWI, MR-based attenuation correction, and PET imaging on a 3.0 T whole-body PET/MR system. ASSESSMENT: The apparent diffusion coefficient (ADC), RSI-derived parameters (restricted diffusion f 1 $$ {f}_1 $$ , hindered diffusion f 2 $$ {f}_2 $$ , and free diffusion f 3 $$ {f}_3 $$ ) and the maximum standardized uptake value (SUVmax) were calculated and analyzed for diagnostic efficacy individually or in combination. STATISTICAL TESTS: Student's t-test, Mann-Whitney U test, receiver operating characteristic (ROC) curves, Delong test, Spearman's correlation analysis. P < 0.05 was considered statistically significant. RESULTS: The f 1 $$ {f}_1 $$ , SUVmax were significantly higher, and f 3 $$ {f}_3 $$ , ADC were significantly lower in the malignant group [0.717 ± 0.131, 9.125 (5.753, 13.058), 0.194 ± 0.099, 1.240 (0.972, 1.407)] compared to the benign group [0.504 ± 0.236, 3.390 (1.673, 6.030), 0.398 ± 0.195, 1.485 ± 0.382]. The area under the ROC curve (AUC) values ranked from highest to lowest as follows: AUC (SUVmax) > AUC ( f 3 $$ {f}_3 $$ ) > AUC ( f 1 $$ {f}_1 $$ ) > AUC (ADC) > AUC ( f 2 $$ {f}_2 $$ ) (AUC = 0.819, 0.811, 0.770, 0.745, 0549). The AUC (AUC = 0.900) of the combined model of RSI with PET was significantly higher than that of either single-modality imaging. CONCLUSION: RSI-derived parameters ( f 1 $$ {f}_1 $$ , f 3 $$ {f}_3 $$ ) might help to distinguish primary benign and malignant lung lesions and the discriminatory utility of f 2 $$ {f}_2 $$ was not observed. The RSI exhibits comparable or potentially enhanced performance compared with DWI, and the combined RSI and PET model might improve diagnostic efficacy. TECHNICAL EFFICACY: Stage 2.

Predicting FDG-PET Images From Multi-Contrast MRI Using Deep Learning in Patients With Brain Neoplasms.

BACKGROUND: 18 F-fluorodeoxyglucose (FDG) positron emission tomography (PET) is valuable for determining presence of viable tumor, but is limited by geographical restrictions, radiation exposure, and high cost. PURPOSE: To generate diagnostic-quality PET equivalent imaging for patients with brain neoplasms by deep learning with multi-contrast MRI. STUDY TYPE: Retrospective. SUBJECTS: Patients (59 studies from 51 subjects; age 56 ± 13 years; 29 males) who underwent 18 F-FDG PET and MRI for determining recurrent brain tumor. FIELD STRENGTH/SEQUENCE: 3T; 3D GRE T1, 3D GRE T1c, 3D FSE T2-FLAIR, and 3D FSE ASL, 18 F-FDG PET imaging. ASSESSMENT: Convolutional neural networks were trained using four MRIs as inputs and acquired FDG PET images as output. The agreement between the acquired and synthesized PET was evaluated by quality metrics and Bland-Altman plots for standardized uptake value ratio. Three physicians scored image quality on a 5-point scale, with score ≥3 as high-quality. They assessed the lesions on a 5-point scale, which was binarized to analyze diagnostic consistency of the synthesized PET compared to the acquired PET. STATISTICAL TESTS: The agreement in ratings between the acquired and synthesized PET were tested with Gwet's AC and exact Bowker test of symmetry. Agreement of the readers was assessed by Gwet's AC. P = 0.05 was used as the cutoff for statistical significance. RESULTS: The synthesized PET visually resembled the acquired PET and showed significant improvement in quality metrics (+21.7% on PSNR, +22.2% on SSIM, -31.8% on RSME) compared with ASL. A total of 49.7% of the synthesized PET were considered as high-quality compared to 73.4% of the acquired PET which was statistically significant, but with distinct variability between readers. For the positive/negative lesion assessment, the synthesized PET had an accuracy of 87% but had a tendency to overcall. CONCLUSION: The proposed deep learning model has the potential of synthesizing diagnostic quality FDG PET images without the use of radiotracers. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 2.

In vivo PET of synaptic density as potential diagnostic marker for cognitive disorders: prospective comparison with current imaging markers for neuronal dysfunction and relation to symptomatology - study protocol.

BACKGROUND: 18F-FDG brain PET is clinically used for differential diagnosis in cognitive dysfunction of unclear etiology and for exclusion of a neurodegenerative cause in patients with cognitive impairment in late-life psychiatric disorders. 18F-FDG PET measures regional glucose metabolism, which represents a combination of neuronal/synaptic activity but also astrocytic activity and neuroinflammation. Recently, imaging of synaptic vesicle protein 2 A (SV2A) has become available and was shown to be a proxy of synaptic density. This prospective study will investigate the use of 18F-SynVesT-1 for imaging SV2A and its discriminative power for differential diagnosis in cognitive disorders in a head-to-head comparison to 18F-FDG PET. In addition, simultaneous PET/MR allows an evaluation of contributing factors and the additional value of advanced MRI imaging to FDG/SV2A PET imaging will be investigated. In this work, the study design and protocol are depicted. METHODS: In this prospective, multimodal imaging study, 110 patients with uncertain diagnosis of cognitive impairment who are referred for 18F-FDG PET brain imaging in their diagnostic work-up in a tertiary memory clinic will be recruited. In addition, 40 healthy volunteers (HV) between 18 and 85 years (M/F) will be included. All study participants will undergo simultaneous 18F-SynVesT-1 PET/MR and an extensive neuropsychological evaluation. Amyloid status will be measured by PET using 18FNAV4694, in HV above 50 years of age. Structural T1-weighted and T2-weighted fluid-attenuated inversion recovery MR images, triple-tagging arterial spin labeling (ASL) and resting-state functional MRI (rs-fMRI) will be obtained. The study has been registered on ClinicalTrials.gov (NCT05384353) and is approved by the local Research Ethics Committee. DISCUSSION: The main endpoint of the study will be the comparison of the diagnostic accuracy between 18F-SynVesT-1 and 18F-FDG PET in cognitive disorders with uncertain etiology and in exclusion of a neurodegenerative cause in patients with cognitive impairment in late-life psychiatric disorders. The strength of the relationship between cognition and imaging data will be assessed, as well as the potential incremental diagnostic value of including MR volumetry, ASL perfusion and rs-fMRI.

Impact of attenuation correction of radiotherapy hardware for positron emission tomography-magnetic resonance in ano-rectal radiotherapy patients.

BACKGROUND: Positron Emission Tomography-Magnetic Resonance (PET-MR) scanners could improve ano-rectal radiotherapy planning through improved Gross Tumour Volume (GTV) delineation and enabling dose painting strategies using metabolic measurements. This requires accurate quantitative PET images acquired in the radiotherapy treatment position. PURPOSE: This study aimed to evaluate the impact on GTV delineation and metabolic parameter measurement of using novel Attenuation Correction (AC) maps that included the radiotherapy flat couch, coil bridge and anterior coil to see if they were necessary. METHODS: Seventeen ano-rectal radiotherapy patients received a 18 F $\mathrm{^{18}F}$ -FluoroDeoxyGlucose PET-MR scan in the radiotherapy position. PET images were reconstructed without ( CTAC std $\mathrm{CTAC_{std}}$ ) and with ( CTAC cba $\mathrm{CTAC_{cba}}$ ) the radiotherapy hardware included. Both AC maps used the same Computed Tomography image for patient AC. Semi-manual and threshold GTVs were delineated on both PET images, the volumes compared and the Dice coefficient calculated. Metabolic parameters: Standardized Uptake Values SUV max $\mathrm{SUV_{max}}$ , SUV mean $\mathrm{SUV_{mean}}$ and Total Lesion Glycolysis (TLG) were compared using paired t-tests with a Bonferroni corrected significance level of p = 0.05 / 8 = 0.006 $p = 0.05/8 = 0.006$ . RESULTS: Differences in semi-manual GTV volumes between CTAC cba $\mathrm{CTAC_{cba}}$ and CTAC std $\mathrm{CTAC_{std}}$ were approaching statistical significance (difference - 15.9 % ± 1.6 % $-15.9\%\pm 1.6\%$ , p = 0.007 $p = 0.007$ ), with larger differences in low FDG-avid tumours ( SUV mean < 8.5 g mL - 1 $\mathrm{SUV_{mean}} < 8.5\;\mathrm{g\: mL^{-1}}$ ). The CTAC cba $\mathrm{CTAC_{cba}}$ and CTAC std $\mathrm{CTAC_{std}}$ GTVs were concordant with Dice coefficients 0.89 ± 0.01 $0.89 \pm 0.01$ (manual) and 0.98 ± 0.00 $0.98 \pm 0.00$ (threshold). Metabolic parameters were significantly different, with SUV max $\mathrm{SUV_{max}}$ , SUV mean $\mathrm{SUV_{mean}}$ and TLG differences of - 11.5 % ± 0.3 % $-11.5\%\ \pm 0.3\%$ ( p < 0.001 $p < 0.001$ ), - 11.6 % ± 0.3 % $-11.6\% \pm 0.3\%$ ( p < 0.001 $p < 0.001$ ) and - 13.7 % ± 0.6 % $-13.7\%\ \pm 0.6\%$ ( p = 0.003 $p = 0.003$ ) respectively. The TLG difference resulted in 1/8 rectal cancer patients changing prognosis group, based on literature TLG cut-offs, when using CTAC cba $\mathrm{CTAC_{cba}}$ rather than CTAC std $\mathrm{CTAC_{std}}$ . CONCLUSIONS: This study suggests that using AC maps with the radiotherapy hardware included is feasible for patient imaging. The impact on tumour delineation was mixed and needs to be evaluated in larger cohorts. However using AC of the radiotherapy hardware is important for situations where accurate metabolic measurements are required, such as dose painting and treatment prognostication.

Presynaptic density determined by SV2A PET is closely associated with postsynaptic metabotropic glutamate receptor 5 availability and independent of amyloid pathology in early cognitive impairment.

INTRODUCTION: Metabotropic glutamate receptor 5 (mGluR5) is involved in regulating integrative brain function and synaptic transmission. Aberrant mGluR5 signaling and relevant synaptic failure play a key role in the pathophysiological mechanism of Alzheimer's disease (AD). METHODS: Ten cognitively impaired (CI) individuals and 10 healthy controls (HCs) underwent [18F]SynVesT-1 and [18F]PSS232 positron emission tomography (PET)/magnetic resonance to assess synaptic density and mGluR5 availability. The associations between mGluR5 availability and synaptic density were examined. A mediation analysis was performed to investigate the possible mediating effects of mGluR5 availability and synaptic loss on the relationship between amyloid deposition and cognition. RESULTS: CI patients exhibited lower mGluR5 availability and synaptic density in the medial temporal lobe than HCs. Regional synaptic density was closely associated with regional mGluR5 availability. mGluR5 availability and synaptic loss partially mediated the relationship between amyloid deposition and cognition. CONCLUSIONS: Reductions in mGluR5 availability and synaptic density exhibit similar spatial patterns in AD and are closely linked. HIGHLIGHTS: Cognitively impaired patients exhibited lower mGluR5 availability and synaptic density in the medial temporal lobe than HCs. Reductions in mGluR5 availability and synaptic density exhibit similar spatial patterns in AD. Regional synaptic density was closely associated with regional mGluR5 availability. mGluR5 availability and synaptic loss partially mediated the relationship between amyloid deposition and global cognition. With further research, modulating mGluR5 availability might be a potential therapeutic strategy for improving synaptic function in AD.

Q.Clear reconstruction for reducing the scanning time for 68 Ga-DOTA-FAPI-04 PET/MR imaging.

PURPOSE: This study aims to determine whether Q.Clear positron emission tomography (PET) reconstruction may reduce tracer injection dose or shorten scanning time in 68Gallium-labelled fibroblast activation protein inhibitor (68 Ga-FAPI) PET/magnetic resonance (MR) imaging. METHODS: We retrospectively collected cases of 68 Ga-FAPI whole-body imaging performed on integrated PET/MR. PET images were reconstructed using three different methods: ordered subset expectation maximization (OSEM) reconstruction with full scanning time, OSEM reconstruction with half scanning time, and Q.Clear reconstruction with half scanning time. We then measured standardized uptake values (SUVs) within and around lesions, alongside their volumes. We also evaluated image quality using lesion-to-background (L/B) ratio and signal-to-noise ratio (SNR). We then compared these metrics across the three reconstruction techniques using statistical methods. RESULTS: Q.Clear reconstruction significantly increased SUVmax and SUVmean within lesions (more than 30%) and reduced their volumes in comparison with OSEM reconstruction. Background SUVmax also increased significantly, while background SUVmean showed no difference. Average L/B values for Q.Clear reconstruction were only marginally higher than those from OSME reconstruction with half-time. SNR decreased significantly in Q.Clear reconstruction compared with OSEM reconstruction with full time (but not half time). Differences between Q.Clear and OSEM reconstructions in SUVmax and SUVmean values within lesions were significantly correlated with SUVs within lesions. CONCLUSIONS: Q.Clear reconstruction was useful for reducing PET injection dose or scanning time while maintaining the image quality. Q.Clear may affect PET quantification, and it is necessary to establish diagnostic recommendations based on Q.Clear results for Q.Clear application.

[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.

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.

PET/MR of pediatric bone tumors: what the radiologist needs to know.

Integrated 2-deoxy-2-[fluorine-18]fluoro-D-glucose (18F-FDG) positron emission tomography (PET)/magnetic resonance (MR) imaging can provide "one stop" local tumor and whole-body staging in one session, thereby streamlining imaging evaluations and avoiding duplicate anesthesia in young children. 18F-FDG PET/MR scans have the benefit of lower radiation, superior soft tissue contrast, and increased patient convenience compared to 18F-FDG PET/computerized tomography scans. This article reviews the 18F-FDG PET/MR imaging technique, reporting requirements, and imaging characteristics of the most common pediatric bone tumors, including osteosarcoma, Ewing sarcoma, primary bone lymphoma, bone and bone marrow metastases, and Langerhans cell histiocytosis.

Diagnostic performance of [18F]-FDG PET/MR in evaluating colorectal cancer: a systematic review and meta-analysis.

PURPOSE: To calculate the diagnostic performance of [18F]-FDG PET/MR in colorectal cancer (CRC). METHODS: This study was designed following the PRISMA-DTA guidelines. To be included, published original articles (until December 31, 2021) that met the following criteria were considered eligible: (1) evaluated [18F]-FDG PET/MR as the diagnostic method to detect CRC; (2) compared [18F]-FDG PET/MR with histopathology as the reference standard, or clinical/imaging composite follow-up when pathology was not available; (3) provided adequate crude data for meta-analysis. The diagnostic pooled measurements were calculated at patient and lesion levels. Regarding sub-group analysis, diagnostic measurements were calculated in "TNM staging," "T staging," "N staging," "M staging," and "liver metastasis" sub-groups. Additionally, we calculated the pooled performances in "rectal cancer: patient-level" and "rectal cancer: lesion-level" sub-groups. A hierarchical method was used to pool the performances. The bivariate model was conducted to find the summary points. Analyses were performed using STATA 16. RESULTS: A total of 1534 patients from 18 studies were entered. The pooled sensitivities in CRC lesion detection (tumor, lymph nodes, and metastases) were 0.94 (95%CI: 0.89-0.97) and 0.93 (95%CI: 0.82-0.98) at patient-level and lesion-level, respectively. The pooled specificities were 0.89 (95%CI: 0.84-0.93) and 0.95 (95%CI: 0.90-0.98) at patient-level and lesion-level, respectively. In sub-groups, the highest sensitivity (0.97, 95%CI: 0.86-0.99) and specificity (0.99, 95%CI: 0.84-1.00) were calculated for "M staging" and "rectal cancer: lesion-level," respectively. The lowest sensitivity (0.81, 95%CI: 0.65-0.91) and specificity (0.79, 95%CI: 0.52-0.93) were calculated for "N staging" and "T staging," respectively. CONCLUSION: This meta-analysis showed an overall high diagnostic performance for [18F]-FDG PET/MR in detecting CRC lesions/metastases. Thus, this modality can play a significant role in several clinical scenarios in CRC staging and restaging. Specifically, one of the main strengths of this modality is ruling out the existence of CRC lesions/metastases. Finally, the overall diagnostic performance was not found to be affected in the post-treatment setting.

Regional glucose metabolic decreases with ageing are associated with microstructural white matter changes: a simultaneous PET/MR study.

PURPOSE: Human ageing is associated with a regional reduction in cerebral neuronal activity as assessed by numerous studies on brain glucose metabolism and perfusion, grey matter (GM) density and white matter (WM) integrity. As glucose metabolism may impact energetics to maintain myelin integrity, but changes in functional connectivity may also alter regional metabolism, we conducted a cross-sectional simultaneous FDG PET/MR study in a large cohort of healthy volunteers with a wide age range, to directly assess the underlying associations between reduced glucose metabolism, GM atrophy and decreased WM integrity in a single ageing cohort. METHODS: In 94 healthy subjects between 19.9 and 82.5 years (mean 50.1 ± 17.1; 47 M/47F, MMSE ≥ 28), simultaneous FDG-PET, structural MR and diffusion tensor imaging (DTI) were performed. Voxel-wise associations between age and grey matter (GM) density, RBV partial-volume corrected (PVC) glucose metabolism, white matter (WM) fractional anisotropy (FA) and mean diffusivity (MD), and age were assessed. Clusters representing changes in glucose metabolism correlating significantly with ageing were used as seed regions for tractography. Both linear and quadratic ageing models were investigated. RESULTS: An expected age-related reduction in GM density was observed bilaterally in the frontal, lateral and medial temporal cortex, striatum and cerebellum. After PVC, relative FDG uptake was negatively correlated with age in the inferior and midfrontal, cingulate and parietal cortex and subcortical regions, bilaterally. FA decreased with age throughout the entire brain WM. Four white matter tracts were identified connecting brain regions with declining glucose metabolism with age. Within these, relative FDG uptake in both origin and target clusters correlated positively with FA (0.32 ≤ r ≤ 0.71) and negatively with MD (- 0.75 ≤ r ≤ - 0.41). CONCLUSION: After appropriate PVC, we demonstrated that regional cerebral glucose metabolic declines with age and that these changes are related to microstructural changes in the interconnecting WM tracts. The temporal course and potential causality between ageing effects on glucose metabolism and WM integrity should be further investigated in longitudinal cohort PET/MR studies.

Comparison of nodal staging between CT, MRI, and [18F]-FDG PET/MRI in patients with newly diagnosed breast cancer.

PURPOSE: To compare CT, MRI, and [18F]-fluorodeoxyglucose positron emission tomography ([18F]-FDG PET/MRI) for nodal status, regarding quantity and location of metastatic locoregional lymph nodes in patients with newly diagnosed breast cancer. MATERIALS AND METHODS: One hundred eighty-two patients (mean age 52.7 ± 11.9 years) were included in this prospective double-center study. Patients underwent dedicated contrast-enhanced chest/abdomen/pelvis computed tomography (CT) and whole-body ([18F]-FDG PET/) magnet resonance imaging (MRI). Thoracal datasets were evaluated separately regarding quantity, lymph node station (axillary levels I-III, supraclavicular, internal mammary chain), and lesion character (benign vs. malign). Histopathology served as reference standard for patient-based analysis. Patient-based and lesion-based analyses were compared by a McNemar test. Sensitivity, specificity, positive and negative predictive values, and accuracy were assessed for all three imaging modalities. RESULTS: On a patient-based analysis, PET/MRI correctly detected significantly more nodal positive patients than MRI (p < 0.0001) and CT (p < 0.0001). No statistically significant difference was seen between CT and MRI. PET/MRI detected 193 lesions in 75 patients (41.2%), while MRI detected 123 lesions in 56 patients (30.8%) and CT detected 104 lesions in 50 patients, respectively. Differences were statistically significant on a lesion-based analysis (PET/MRI vs. MRI, p < 0.0001; PET/MRI vs. CT, p < 0.0001; MRI vs. CT, p = 0.015). Subgroup analysis for different lymph node stations showed that PET/MRI detected significantly more lymph node metastases than MRI and CT in each location (axillary levels I-III, supraclavicular, mammary internal chain). MRI was superior to CT only in axillary level I (p = 0.0291). CONCLUSION: [18F]-FDG PET/MRI outperforms CT or MRI in detecting nodal involvement on a patient-based analysis and on a lesion-based analysis. Furthermore, PET/MRI was superior to CT or MRI in detecting lymph node metastases in all lymph node stations. Of all the tested imaging modalities, PET/MRI showed the highest sensitivity, whereas CT showed the lowest sensitivity, but was most specific.

The effect of modern PET technology and techniques on the EANM paediatric dosage card.

AIM: Recent advancements in PET technology have brought with it significant improvements in PET performance and image quality. In particular, the extension of the axial field of view of PET systems, and the introduction of semiconductor technology into the PET detector, initially for PET/MR, and more recently available long-field-of-view PET/CT systems (≥ 25 cm) have brought a step change improvement in the sensitivity of PET scanners. Given the requirement to limit paediatric doses, this increase in sensitivity is extremely welcome for the imaging of children and young people. This is even more relevant with PET/MR, where the lack of CT exposures brings further dose reduction benefits to this population. In this short article, we give some details around the benefits around new PET technology including PET/MR and its implications on the EANM paediatric dosage card. MATERIAL AND METHODS : Reflecting on EANM adult guidance on injected activities, and making reference to bed overlap and the concept of MBq.min bed-1 kg-1, we use published data on image quality from PET/MR systems to update the paediatric dosage card for PET/MR and extended axial field of view (≥ 25 cm) PET/CT systems. However, this communication does not cover the expansion of paediatric dosing for the half-body and total-body scanners that have recently come to market. RESULTS: In analogy to the existing EANM dosage card, new parameters for the EANM paediatric dosage card were developed (class B, baseline value: 10.7 MBq, minimum recommended activity 10 MBq). The recommended administered activities for the systems considered in this communication range from 11 MBq [18F]FDG for a child with a weight of 3 kg to 149 MBq [18F]FDG for a paediatric patient weight of 68 kg, assuming a scan of 3 min per bed position. The mean effective dose over all ages (1 year and older) is 2.85 mSv. CONCLUSION: With this, recommendations for paediatric dosing are given for systems that have not been considered previously.

Decoupling of regional neural activity and inter-regional functional connectivity in Alzheimer's disease: a simultaneous PET/MR study.

PURPOSE: Alzheimer's disease (AD) and mild cognitive impairment (MCI) are characterized by both aberrant regional neural activity and disrupted inter-regional functional connectivity (FC). However, the effect of AD/MCI on the coupling between regional neural activity (measured by regional fluorodeoxyglucose imaging (rFDG)) and inter-regional FC (measured by resting-state functional magnetic resonance imaging (rs-fMRI)) is poorly understood. METHODS: We scanned 19 patients with MCI, 33 patients with AD, and 26 healthy individuals by simultaneous FDG-PET/rs-fMRI and assessed rFDG and inter-regional FC metrics (i.e., clustering coefficient and degree centrality). Next, we examined the potential moderating effect of disease status (MCI or AD) on the link between rFDG and inter-regional FC metrics using hierarchical moderated multiple regression analysis. We also tested this effect by considering interaction between disease status and inter-regional FC metrics, as well as interaction between disease status and rFDG. RESULTS: Our findings revealed that both rFDG and inter-regional FC metrics were disrupted in MCI and AD. Moreover, AD altered the relationship between rFDG and inter-regional FC metrics. In particular, we found that AD moderated the effect of inter-regional FC metrics of the caudate, parahippocampal gyrus, angular gyrus, supramarginal gyrus, frontal pole, inferior temporal gyrus, middle frontal, lateral occipital, supramarginal gyrus, precuneus, and thalamus on predicting their rFDG. On the other hand, AD moderated the effect of rFDG of the parietal operculum on predicting its inter-regional FC metric. CONCLUSION: Our findings demonstrated that AD decoupled the link between regional neural activity and functional segregation and global connectivity across particular brain regions.

Effects of MRI protocols on brain FDG uptake in simultaneous PET/MR imaging.

PURPOSE: To investigate the potential effects of MRI protocols on brain FDG uptake in simultaneous PET/MR imaging. METHODS: Seventy healthy subjects and ten patients with temporal lobe epilepsy were enrolled. Healthy subjects were divided to three groups to undergo different PET/MR scan protocols: "continuous MRI" with MRI stimulation presented during the whole scan, "late MRI" with MRI stimulation started after 40 min glucose uptake, and "no MRI" without MRI stimulation at all. Region-wise and voxel-wise differences in FDG uptake among the three protocols were compared. All epilepsy patients were scanned with the "continuous MRI" scan protocol. The effects of MRI protocol stimulation on pathological interpretation were evaluated. RESULTS: Highest global averaged metabolism was found in the normal dataset with continuous MRI scan protocol (P < 0.05). Specifically, we observed higher FDG uptake in the primary auditory cortex, putamen, and lower FDG uptake in the occipital lobe and cerebellum during the "continuous MRI" scan protocol. However, MRI protocol stimulation after 40 min glucose uptake did not cause any significant differences in FDG uptake. Respectively compared to the normal dataset, patients with epilepsy showed consistent hypometabolism in the temporal lobe. Besides, significant metabolism changes in the primary auditory cortex, vermis, and occipital lobe were found in the "late MRI" protocol. CONCLUSION: The effects of MRI protocol on brain FDG uptake were varied. The effects, including from other practical setting, were conspicuous for scans where MRI protocol started immediately after glucose uptake, but would dramatically decrease to negligible 40 min later. Hence, it would be necessary for pathology studies to collect data from a normal control group using the same scan protocol for unbiased evaluation.

Comparison of the diagnostic efficacy of 68 Ga-FAPI-04 PET/MR and 18F-FDG PET/CT in patients with pancreatic cancer.

PURPOSE: We sought to assess the performance of 68 Ga-FAPI-04 PET/MR for the diagnosis of primary tumours as well as metastatic lesions in patients with pancreatic cancer and to compare the results with those of 18F-FDG PET/CT. METHODS: Prospectively, we evaluated 33 patients suspected to have pancreatic adenocarcinoma, of whom thirty-two were confirmed by histopathology, and one had autoimmune pancreatitis confirmed by needle biopsy and glucocorticoid treatment. Within 1 week, each patient underwent both 68 Ga-FAPI-04 PET/MR and 18F-FDG PET/CT. Comparisons of the detection abilities for primary tumours, lymph nodes, and metastases were conducted for the two imaging approaches. The original maximum standard uptake values (SUVmax) and normalised SUVmax (SUVmax/SUVbkgd) of paired lesions on 68 Ga-FAPI-04 PET/MR and 18F-FDG PET/CT were measured and compared. RESULTS: Thirty pancreatic cancer patients and three pancreatitis patients were enrolled. 68 Ga-FAPI-04 PET/MR and 18F-FDG PET/CT exhibited equivalent (100%) detection rates for primary tumours. The original/normalised SUVmax of primary tumours on 68 Ga-FAPI-04 PET was markedly higher than that on 18F-FDG (p < 0.05). Sixteen pancreatic cancer patients had pancreatic parenchymal uptake, whereas 18F-FDG PET images showed parenchymal uptake in only four patients (53.33% vs. 13.33%, p < 0.001). 68 Ga-FAPI-04 PET detected more positive lymph nodes than 18F-FDG PET (42 vs. 30, p < 0.001), while 18F-FDG PET was able to detect more liver metastases than 68 Ga-FAPI-04 (181 vs. 104, p < 0.001). In addition, multisequence MR imaging helped explain ten pancreatic cancers that could not be definitively revealed due to 68 Ga-FAPI-04 inflammatory uptake and identified more liver metastases than 18F-FDG (256 vs. 181, p < 0.001). CONCLUSION: 68 Ga-FAPI-04 PET might be better than 18F-FDG PET in the detection of suspicious lymph node metastases. MR multiple sequence imaging of 68 Ga-FAPI-04 PET/MR was helpful for explaining pancreatic lesions in patients with obstructive inflammation and detecting tiny liver metastases.