The role of 18F-FDG PET in minimizing variability in gross tumor volume delineation of soft tissue sarcomas.

BACKGROUND: Accurate gross tumor volume (GTV) delineation is a critical step in radiation therapy treatment planning. However, it is reader dependent and thus susceptible to intra- and inter-reader variability. GTV delineation of soft tissue sarcoma (STS) often relies on CT and MR images. PURPOSE: This study investigates the potential role of 18F-FDG PET in reducing intra- and inter-reader variability thereby improving reproducibility of GTV delineation in STS, without incurring additional costs or radiation exposure. MATERIALS AND METHODS: Three readers performed independent GTV delineation of 61 patients with STS using first CT and MR followed by CT, MR, and 18F-FDG PET images. Each reader performed a total of six delineation trials, three trials per imaging modality group. Dice Similarity Coefficient (DSC) score and Hausdorff distance (HD) were used to assess both intra- and inter-reader variability using generated simultaneous truth and performance level estimation (STAPLE) GTVs as ground truth. Statistical analysis was performed using a Wilcoxon signed-ranked test. RESULTS: There was a statistically significant decrease in both intra- and inter-reader variability in GTV delineation using CT, MR 18F-FDG PET images vs. CT and MR images. This was translated by an increase in the DSC score and a decrease in the HD for GTVs drawn from CT, MR and 18F-FDG PET images vs. GTVs drawn from CT and MR for all readers and across all three trials. CONCLUSION: Incorporation of 18F-FDG PET into CT and MR images decreased intra- and inter-reader variability and subsequently increased reproducibility of GTV delineation in STS.

Interim FDG-PET improves treatment failure prediction in primary central nervous system Lymphoma: a LOC network prospective multicentric study.

PURPOSE: The purpose of our study was to assess the predictive and prognostic role of 2-18F-fluoro-2-deoxy-D-glucose (FDG) PET/MRI during high-dose methotrexate-based chemotherapy (HD-MBC) in de novo primary central nervous system lymphoma (PCNSL) patients aged 60 and above. METHODS: This prospective multicentric ancillary study included 65 immunocompetents patients who received induction HD-MBC as part of the BLOCAGE01 phase III trial. FDG-PET/MRI were acquired at baseline, post two cycles (PET/MRI2), and post-treatment (PET/MRI3). FDG-PET response was dichotomized, with "positive" indicating persistent tumor uptake higher than the contralateral mirroring brain region. Performances of FDG-PET and International PCNSL Collaborative Group criteria in predicting induction response, progression-free survival (PFS), and overall survival (OS) were compared. RESULTS: Of 48 PET2 scans performed, nine were positive and aligned with a partial response (PR) on MRI2. Among these, eight (89%) progressed by the end of the induction phase. In contrast, 35/39 (90%) of PET2-negative patients achieved complete response (CR). Among the 18 discordant responses at interim (PETCR/MRIPR), 83% ultimately achieved CR. 87% of the PET2-negative patients were disease-free at 6 months versus 11% of the PET2-positive patients (p<0.001). The MRI2 response did not significantly differentiate patients based on their PFS, regardless of whether they were in CR or PR. Both PET2 and MRI2 independently predicted OS in multivariate analysis, with PET2 showing stronger association. CONCLUSION: Our study highlights the potential of interim FDG-PET for early management of PCNSL patients. Response-driven treatment based on PET2 may guide future clinical trials.

Exploring the mechanism of 18F-fluorodopa uptake in recurrent high-grade gliomas: A comprehensive histomolecular-positron emission tomography analysis.

BACKGROUND: Dihydroxy-6-[18F]fluoro-L-phenylalanine (18F-FDOPA) positron emission tomography (PET) is a valuable tool for managing high-grade gliomas (HGGs), but there is a lack of literature on its relationship with glioma subtypes since the 2021 reclassification of brain tumors. There is also debate surrounding the mechanism of 18F-FDOPA uptake, particularly after chemoradiation therapy. This study aimed to investigate the correlation between 18F-FDOPA uptake and histomolecular characteristics, particularly L-amino acid transporter 1 (LAT1) expression, in recurrent gliomas, and examine their impact on survival in HGGs. METHODS: Thirty-nine patients with recurrent HGGs (14 isocitrate dehydrogenase [IDH]-mutant, 25 IDH-wildtype) who underwent a brain 18F-FDOPA PET/computed tomography (CT) or PET/magnetic resonance imaging (MRI) followed by surgical resection of the 18F-FDOPA-avid lesion within 6 months, were retrospectively reviewed. PET results were compared with histological examination and for SCL7A5/LAT1 immunostaining. The study also examined the relationship between PET parameters, LAT1 expression, and survival outcomes. RESULTS: Astrocytoma IDH-mutant G4 had higher 18F-FDOPA uptake than glioblastoma IDH-wildtype G4 (maximum tumor-to-normal brain ratio [TBRmax] 5 [3.4-9] vs. 3.8 [2.8-5.9], p = 0.02). IDH-mutant gliomas had higher LAT1 expression than IDH-wildtype gliomas (100 [14-273] vs. 15.5 [0-137], p < 0.05) as well as higher TBRmax (5 [2.4-9] vs. 3.8 [2.8-6], p < 0.05). In survival analysis, LAT1 score >100 was a predictor for longer progression-free survival in IDH-mutant HGGs. CONCLUSIONS: To our knowledge, our study is the first to suggest a link between LAT1 expression and IDH mutation status. We showed that higher TBRmax was associated with higher LAT1 expression and IDH mutation status. Further studies are needed to better understand the mechanisms underlying amino acid PET tracers uptake, especially in the post-radiation and chemotherapy settings.

Image-Guided Precision Medicine in the Diagnosis and Treatment of Pheochromocytomas and Paragangliomas.

In this comprehensive review, we aimed to discuss the current state-of-the-art medical imaging for pheochromocytomas and paragangliomas (PPGLs) diagnosis and treatment. Despite major medical improvements, PPGLs, as with other neuroendocrine tumors (NETs), leave clinicians facing several challenges; their inherent particularities and their diagnosis and treatment pose several challenges for clinicians due to their inherent complexity, and they require management by multidisciplinary teams. The conventional concepts of medical imaging are currently undergoing a paradigm shift, thanks to developments in radiomic and metabolic imaging. However, despite active research, clinical relevance of these new parameters remains unclear, and further multicentric studies are needed in order to validate and increase widespread use and integration in clinical routine. Use of AI in PPGLs may detect changes in tumor phenotype that precede classical medical imaging biomarkers, such as shape, texture, and size. Since PPGLs are rare, slow-growing, and heterogeneous, multicentric collaboration will be necessary to have enough data in order to develop new PPGL biomarkers. In this nonsystematic review, our aim is to present an exhaustive pedagogical tool based on real-world cases, dedicated to physicians dealing with PPGLs, augmented by perspectives of artificial intelligence and big data.

Clinical Value of Hybrid PET/MR Imaging: Brain Imaging Using PET/MR Imaging.

Hybrid PET/MR imaging offers a unique opportunity to acquire MR imaging and PET information during a single imaging session. PET/MR imaging has numerous advantages, including enhanced diagnostic accuracy, improved disease characterization, and better treatment planning and monitoring. It enables the immediate integration of anatomic, functional, and metabolic imaging information, allowing for personalized characterization and monitoring of neurologic diseases. This review presents recent advances in PET/MR imaging and highlights advantages in clinical practice for neuro-oncology, epilepsy, and neurodegenerative disorders. PET/MR imaging provides valuable information about brain tumor metabolism, perfusion, and anatomic features, aiding in accurate delineation, treatment response assessment, and prognostication.

[18F]FDG PET-MRI provides survival biomarkers in primary central nervous system lymphoma in the elderly: an ancillary study from the BLOCAGE trial of the LOC network.

PURPOSE: Primary central nervous system lymphoma (PCNSL) incidence is rising among elderly patients, presenting challenges due to poor prognosis and treatment-related toxicity risks. This study explores the potential of combining [18F]fluorodeoxyglucose ([18F]FDG) PET scans and multimodal MRI for improving management in elderly patients with de novo PCNSL. METHODS: Immunocompetent patients over 60 years with de novo PCNSL were prospectively enrolled in a multicentric study between January 2016 and April 2021. Patients underwent brain [18F]FDG PET-MRI before receiving high-dose methotrexate-based chemotherapy. Relationships between extracted PET (metabolic tumor volume (MTV), sum of MTV for up to five lesions (sumMTV), metabolic imaging lymphoma aggressiveness score (MILAS)) and MRI parameters (tumor contrast-enhancement size, cerebral blood volume (CBV), cerebral blood flow (CBF), apparent diffusion coefficient (ADC)) and treatment response and outcomes were analyzed. RESULTS: Of 54 newly diagnosed diffuse large B-cell PCNSL patients, 52 had positive PET and MRI with highly [18F]FDG-avid and contrast-enhanced disease (SUVmax: 27.7 [22.8-36]). High [18F]FDG uptake and metabolic volume were significantly associated with low ADCmean values and high CBF at baseline. Among patients, 69% achieved an objective response at the end of induction therapy, while 17 were progressive. Higher cerebellar SUVmean and lower sumMTV at diagnosis were significant predictors of complete response: 6.4 [5.7-7.7] vs 5.4 [4.5-6.6] (p = 0.04) and 5.5 [2.1-13.3] vs 15.9 [4.2-19.5] (p = 0.01), respectively. Two-year overall survival (OS) was 71%, with a median progression-free survival (PFS) of 29.6 months and a median follow-up of 37 months. Larger tumor volumes on PET or enhanced T1-weighted MRI were significant predictors of poorer OS, while a high MILAS score at diagnosis was associated with early death (< 1 year). CONCLUSION: Baseline cerebellar metabolism and sumMTV may predict response to end of chemotherapy in PCNSL. Tumor volume and MILAS at baseline are strong prognostic factors.

Differentiating high-grade glioma progression from treatment-related changes with dynamic [18F]FDOPA PET: a multicentric study.

OBJECTIVES: Diagnostic accuracy of amino-acid PET for distinguishing progression from treatment-related changes (TRC) is currently based on single-center non-homogeneous glioma populations. Our study assesses the diagnostic value of static and dynamic [18F]FDOPA PET acquisitions to differentiate between high-grade glioma (HGG) recurrence and TRC in a large cohort sourced from two independent nuclear medicine centers. METHODS: We retrospectively identified 106 patients with suspected glioma recurrences (WHO GIII, n = 38; GIV, n = 68; IDH-mutant, n = 35, IDH-wildtype, n = 71). Patients underwent dynamic [18F]FDOPA PET/CT (n = 83) or PET/MRI (n = 23), and static tumor-to-background ratios (TBRs), metabolic tumor volumes and dynamic parameters (time to peak and slope) were determined. The final diagnosis was either defined by histopathology or a clinical-radiological follow-up at 6 months. Optimal [18F]FDOPA PET parameter cut-offs were obtained by receiver operating characteristic analysis. Predictive factors and clinical parameters were assessed using univariate and multivariate Cox regression survival analyses. RESULTS: Surgery or the clinical-radiological 6-month follow-up identified 71 progressions and 35 treatment-related changes. TBRmean, with a threshold of 1.8, best-differentiated glioma recurrence/progression from post-treatment changes in the whole population (sensitivity 82%, specificity 71%, p < 0.0001) whereas curve slope was only significantly different in IDH-mutant HGGs (n = 25). In survival analyses, MTV was a clinical independent predictor of progression-free and overall survival on the multivariate analysis (p ≤ 0.01). A curve slope > -0.12/h was an independent predictor for longer PFS in IDH-mutant HGGs CONCLUSION: Our multicentric study confirms the high accuracy of [18F]FDOPA PET to differentiate recurrent malignant gliomas from TRC and emphasizes the diagnostic and prognostic value of dynamic acquisitions for IDH-mutant HGGs. KEY POINTS: • The diagnostic accuracy of dynamic amino-acid PET, for distinguishing progression from treatment-related changes, is currently based on single-center non-homogeneous glioma populations. • This multicentric study confirms the high accuracy of static [18F]FDOPA PET images for differentiating progression from treatment-related changes in a homogeneous population of high-grade gliomas and highlights the diagnostic and prognostic value of dynamic acquisitions for IDH-mutant high-grade gliomas. • Dynamic acquisitions should be performed in IDH-mutant glioma patients to provide valuable information for the differential diagnosis of recurrence and treatment-related changes.

Role of Positron Emission Tomography in Primary Central Nervous System Lymphoma.

The incidence of primary central nervous system lymphoma has increased over the past two decades in immunocompetent patients and the prognosis remains poor. A diagnosis and complete evaluation of the patient is needed without delay, but histologic evaluation is not always available and PCNSL can mimic a variety of brain lesions on MRI. In this article, we review the potential role of 18F-FDG PET for the diagnosis of PCNSL in immunocompetent and immunocompromised patients. Its contribution to systemic assessment at the time of diagnosis has been well established by expert societies over the past decade. In addition, 18F-FDG provides valuable information for differential diagnosis and outcome prediction. The literature also shows the potential role of 18F-FDG as a therapeutic evaluation tool during the treatment and the end of the treatment. Finally, we present several new radiotracers that may have a potential role in the management of PCNSL in the future.

Hybrid [18F]-F-DOPA PET/MRI Interpretation Criteria and Scores for Glioma Follow-up After Radiotherapy.

OBJECTIVE: 18F­fluoro-L­3,4­dihydroxyphenylalanine positron emission tomography (F­DOPA PET) is used in glioma follow-up after radiotherapy to discriminate treatment-related changes (TRC) from tumor progression (TP). We compared the performances of a combined PET and MRI analysis with F­DOPA current standard of interpretation. METHODS: We included 76 consecutive patients showing at least one gadolinium-enhanced lesion on the T1­w MRI sequence (T1G). Two nuclear medicine physicians blindly analyzed PET/MRI images. In addition to the conventional PET analysis, they looked for F­DOPA uptake(s) outside T1G-enhanced areas (T1G/PET), in the white matter (WM/PET), for T1G-enhanced lesion(s) without sufficiently concordant F­DOPA uptake (T1G+/PET), and F­DOPA uptake(s) away from hemorrhagic changes as shown with a susceptibility weighted imaging sequence (SWI/PET). We measured lesions' F­DOPA uptake ratio using healthy brain background (TBR) and striatum (T/S) as references, and lesions' perfusion with arterial spin labelling cerebral blood flow maps (rCBF). Scores were determined by logistic regression. RESULTS: 53 and 23 patients were diagnosed with TP and TRC, respectively. The accuracies were 74% for T/S, 76% for TBR, and 84% for rCBF, with best cut-off values of 1.3, 3.7 and 1.25, respectively. For hybrid variables, best accuracies were obtained with conventional analysis (82%), T1G+/PET (82%) and SWI/PET (81%). T1G+/PET, SWI/PET and rCBF ≥ 1.25 were selected to construct a 3-point score. It outperformed conventional analysis and rCBF with an AUC of 0.94 and an accuracy of 87%. CONCLUSIONS: Our scoring approach combining F­DOPA PET and MRI provided better accuracy than conventional PET analyses for distinguishing TP from TRC in our patients after radiation therapy.

Relevance of Dynamic 18F-DOPA PET Radiomics for Differentiation of High-Grade Glioma Progression from Treatment-Related Changes.

This study evaluates the relevance of 18F-DOPA PET static and dynamic radiomics for differentiation of high-grade glioma (HGG) progression from treatment-related changes (TRC) by comparing diagnostic performances to the current PET imaging standard of care. Eighty-five patients with histologically confirmed HGG and investigated by dynamic 18F-FDOPA PET in two institutions were retrospectively selected. ElasticNet logistic regression, Random Forest and XGBoost machine models were trained with different sets of features-radiomics extracted from static tumor-to-background-ratio (TBR) parametric images, radiomics extracted from time-to-peak (TTP) parametric images, as well as combination of both-in order to discriminate glioma progression from TRC at 6 months from the PET scan. Diagnostic performances of the models were compared to a logistic regression model with TBRmean ± clinical features used as reference. Training was performed on data from the first center, while external validation was performed on data from the second center. Best radiomics models showed only slightly better performances than the reference model (respective AUCs of 0.834 vs. 0.792, p < 0.001). Our current results show similar findings at the multicentric level using different machine learning models and report a marginal additional value for TBR static and TTP dynamic radiomics over the classical analysis based on TBR values.

Updated Trends in Imaging Practices for Pancreatic Neuroendocrine Tumors (PNETs): A Systematic Review and Meta-Analysis to Pave the Way for Standardization in the New Era of Big Data and Artificial Intelligence.

PURPOSE: Medical imaging plays a central and decisive role in guiding the management of patients with pancreatic neuroendocrine tumors (PNETs). Our aim was to synthesize all recent literature of PNETs, enabling a comparison of all imaging practices. METHODS: based on a systematic review and meta-analysis approach, we collected; using MEDLINE, EMBASE, and Cochrane Library databases; all recent imaging-based studies, published from December 2014 to December 2019. Study quality assessment was performed by QUADAS-2 and MINORS tools. RESULTS: 161 studies consisting of 19852 patients were included. There were 63 'imaging' studies evaluating the accuracy of medical imaging, and 98 'clinical' studies using medical imaging as a tool for response assessment. A wide heterogeneity of practices was demonstrated: imaging modalities were: CT (57.1%, n=92), MR (42.9%, n=69), PET/CT (13.3%, n=31), and SPECT/CT (9.3%, n=15). International imaging guidelines were mentioned in 2.5% (n=4/161) of studies. In clinical studies, imaging protocol was not mentioned in 30.6% (n=30/98) of cases and only mentioned imaging modality without further information in 63.3% (n=62/98), as compared to imaging studies (1.6% (n=1/63) of (p<0.001)). QUADAS-2 and MINORS tools deciphered existing biases in the current literature. CONCLUSION: We provide an overview of the updated current trends in use of medical imaging for diagnosis and response assessment in PNETs. The most commonly used imaging modalities are anatomical (CT and MRI), followed by PET/CT and SPECT/CT. Therefore, standardization and homogenization of PNETs imaging practices is needed to aggregate data and leverage a big data approach for Artificial Intelligence purposes.

Contribution of PET-MRI in brain diseases in clinical practice.

PURPOSE OF REVIEW: Hybrid PET- MRI is a technique that has the ability to improve diagnostic accuracy in many applications, whereas PET and MRI performed separately often fail to provide accurate responses to clinical questions. Here, we review recent studies and current developments in PET-MRI, focusing on clinical applications. RECENT FINDINGS: The combination of PET and MRI imaging methods aims at increasing the potential of each individual modality. Combined methods of image reconstruction and correction of PET-MRI attenuation are being developed, and a number of applications are being introduced into clinical practice. To date, the value of PET-MRI has been demonstrated for the evaluation of brain tumours in epilepsy and neurodegenerative diseases. Continued advances in data analysis regularly improve the efficiency and the potential application of multimodal biomarkers. SUMMARY: PET-MRI provides simultaneous of anatomical, functional, biochemical and metabolic information for the personalized characterization and monitoring of neurological diseases. In this review, we show the advantage of the complementarity of different biomarkers obtained using PET-MRI data. We also present the recent advances made in this hybrid imaging modality and its advantages in clinical practice compared with MRI and PET separately.

18F-FDOPA PET/CT Findings in a Patient With Primary Cerebral Amyloidoma.

Amino acid PET, including F-FDOPA, is recommended for initial characterization, delineation of tumor extent, and follow-up of gliomas because of its high diagnostic performances. F-FDOPA accumulates inside tumor cells via the L-type amino acid transporter 1 (LAT1) whose expression is increased in gliomas. We report here a case of a histopathologically proven brain amyloidoma that was first addressed for a suspected glioma. Congo red staining showed scattered extracellular deposits of amyloid and immunohistochemistry-highlighted LAT1 expression, explaining the high F-FDOPA uptake found in this lesion. This case indicates that differential diagnosis of the F-FDOPA uptake in brain lesions should include amyloidoma.

Imaging-guided precision medicine in non-resectable gastro-entero-pancreatic neuroendocrine tumors: A step-by-step approach.

The majority of gastroenteropancreatic (GEP) neuroendocrine tumors (NETs) are diagnosed at a non-resectable stage due to non-specific clinical syndromes, late manifestations from mass effects, or incidental detection of a clinically silent disease. Management strategies include curative or cytoreduction surgery, imaging-guided intervention, chemotherapy, immunotherapy, and radionuclide therapies. In this step-by-step review, we provide a structured approach for standardized reading and reporting of medical imaging studies covering content and terminology. This review explains which imaging studies should be used for different NETs and what should be reported when interpreting these studies. This standardized data collection guide should enable precision medicine for the management of patients with GEP-NETs of neuroectodermal origin: gastrointestinal-NETs (giNETs) and pancreatic NETs (pNETs). To improve outcomes from GEP-NETs, it contains a comprehensive evaluation of imaging aids for determining surgical non-resectability, and serves as a surrogate measure for tumor differentiation and proliferation, assessing the spatial and temporal heterogeneity of the tumor sites with prognostic and therapeutic implications.

The role of multimodal imaging in guiding resectability and cytoreduction in pancreatic neuroendocrine tumors: focus on PET and MRI.

Pancreatic neuroendocrine tumors (pNETs) are rare neoplasms that secrete peptides and neuro-amines. pNETs can be sporadic or hereditary, syndromic or non-syndromic with different clinical presentations and prognoses. The role of medical imaging includes locating the tumor, assessing its extent, and evaluating the feasibility of curative surgery or cytoreduction. Pancreatic NETs have very distinctive phenotypes on CT, MRI, and PET. PET have been demonstrated to be very sensitive to detect either well-differentiated pNETs using 68Gallium somatostatin receptor (SSTR) radiotracers, or more aggressive undifferentiated pNETS using 18F-FDG. A comprehensive interpretation of multimodal imaging guides resectability and cytoreduction in pNETs. The imaging phenotype provides information on the differentiation and proliferation of pNETs, as well as the spatial and temporal heterogeneity of tumors with prognostic and therapeutic implications. This review provides a structured approach for standardized reading and reporting of medical imaging studies with a focus on PET and MR techniques. It explains which imaging approach should be used for different subtypes of pNET and what a radiologist should be looking for and reporting when interpreting these studies.