Assessment of structural disconnections in gliomas: comparison of indirect and direct approaches.

Gliomas are amongst the most common primary brain tumours in adults and are often associated with poor prognosis. Understanding the extent of white matter (WM) which is affected outside the tumoral lesion may be of paramount importance to explain cognitive deficits and the clinical progression of the disease. To this end, we explored both direct (i.e., tractography based) and indirect (i.e., atlas-based) approaches to quantifying WM structural disconnections in a cohort of 44 high- and low-grade glioma patients. While these methodologies have recently gained popularity in the context of stroke and other pathologies, to our knowledge, this is the first time they are applied in patients with brain tumours. More specifically, in this work, we present a quantitative comparison of the disconnection maps provided by the two methodologies by applying well-known metrics of spatial similarity, extension, and correlation. Given the important role the oedematous tissue plays in the physiopathology of tumours, we performed these analyses both by including and excluding it in the definition of the tumoral lesion. This was done to investigate possible differences determined by this choice. We found that direct and indirect approaches offer two distinct pictures of structural disconnections in patients affected by brain gliomas, presenting key differences in several regions of the brain. Following the outcomes of our analysis, we eventually discuss the strengths and pitfalls of these two approaches when applied in this critical field.

PET/MR in recurrent glioblastoma patients treated with regorafenib: [18F]FET and DWI-ADC for response assessment and survival prediction.

OBJECTIVE: The use of regorafenib in recurrent glioblastoma patients has been recently approved by the Italian Medicines Agency (AIFA) and added to the National Comprehensive Cancer Network (NCCN) 2020 guidelines as a preferred regimen. Given its complex effects at the molecular level, the most appropriate imaging tools to assess early response to treatment is still a matter of debate. Diffusion-weighted imaging and O-(2-18F-fluoroethyl)-L-tyrosine positron emission tomography ([18F]FET PET) are promising methodologies providing additional information to the currently used RANO criteria. The aim of this study was to evaluate the variations in diffusion-weighted imaging/apparent diffusion coefficient (ADC) and [18F]FET PET-derived parameters in patients who underwent PET/MR at both baseline and after starting regorafenib. METHODS: We retrospectively reviewed 16 consecutive GBM patients who underwent [18F]FET PET/MR before and after two cycles of regorafenib. Patients were sorted into stable (SD) or progressive disease (PD) categories in accordance with RANO criteria. We were also able to analyze four SD patients who underwent a third PET/MR after another four cycles of regorafenib. [18F]FET uptake greater than 1.6 times the mean background activity was used to define an area to be superimposed on an ADC map at baseline and after treatment. Several metrics were then derived and compared. Log-rank test was applied for overall survival analysis. RESULTS: Percentage difference in FET volumes correlates with the corresponding percentage difference in ADC (R = 0.54). Patients with a twofold increase in FET after regorafenib showed a significantly higher increase in ADC pathological volume than the remaining subjects (p = 0.0023). Kaplan-Meier analysis, performed to compare the performance in overall survival prediction, revealed that the percentage variations of FET- and ADC-derived metrics performed at least as well as RANO criteria (p = 0.02, p = 0.024 and p = 0.04 respectively) and in some cases even better. TBR Max and TBR mean are not able to accurately predict overall survival. CONCLUSION: In recurrent glioblastoma patients treated with regorafenib, [18F]FET and ADC metrics, are able to predict overall survival and being obtained from completely different measures as compared to RANO, could serve as semi-quantitative independent biomarkers of response to treatment. ADVANCES IN KNOWLEDGE: Simultaneous evaluation of [18F]FET and ADC metrics using PET/MR allows an early and reliable identification of response to treatment and predict overall survival.

Volumetric histograms-based analysis of apparent diffusion coefficients and standard uptake values for the assessment of pediatric sarcoma at staging: preliminary results of a PET/MRI study.

PURPOSE: To assess the relationship between apparent diffusion coefficients (ADC) and standard uptake values (SUV) of pediatric sarcomas at staging by using volumetric histograms analyses. METHODS: Children with histologically proven sarcoma, referring to our tertiary center for a whole-body 18F-FDG PET/MRI for staging and including diffusion weighted imaging in the MRI protocol were investigated. Firstly, turbo inversion recovery magnitude (TIRM) and PET images were resliced and resampled according to the ADC maps. Regions of interests were drawn along tumor margins on TIRM images and then copied on PET and ADC datasets. Pixel-based SUVs and ADCs were collected from the entire volume of each lesion. Mean, median, skewness, and kurtosis of SUVs and ADCs values were computed, and the Pearson correlation coefficient was then applied (for the entire population and for histological subgroups with more than five patients). RESULTS: Thirteen patients met the inclusion criteria (six females; mean age 8.31 ± 6.03 years). Histology revealed nine rhabdomyosarcomas, three Ewing sarcomas, and one chondroblastic osteosarcoma. A significant negative correlation between ADCs' and SUVs' mean (rmean = - 0.501, P < 0.001), median (rmedian = - 0.519, P < 0,001), and skewness (rskewness = - 0.550, P < 0.001) emerged for the entire population and for rhabdomyosarcomas (rmean = - 0.541, P = 0.001, rmedian = - 0.597, P < 0.001, rskewness = - 0.568, P < 0.001), whereas a significant positive correlation was found for kurtosis (rkurtosis = 0.346, P < 0.001, and rkurtosis = 0.348, P < 0.001 for the entire population and for rhabdomyosarcomas, respectively). CONCLUSION: Our preliminary results demonstrate that, using volumetric histograms, simultaneously collected SUVs and ADCs are dependent biomarkers in pediatric FDG-avid sarcomas. Further studies, on a larger population, are necessary to confirm this evidence and assess its clinical implications.

10-Year Clinical Experience With 18F-Choline PET/CT: An Italian Multicenter Retrospective Assessment of 3343 Patients.

PURPOSE: The primary aim of this multicenter retrospective analysis is to examine the role of F-choline PET/CT as a diagnostic tool for staging and restaging prostate cancer (PCa) in a large population in the light of 10 years of clinical experience. A secondary aim of the study is to produce data on the predictors of a positive F-choline PET/CT result in the setting of PCa primaries and biochemical recurrences. MATERIALS AND METHODS: This multicenter retrospective cohort study is based on data collected by 9 Italian nuclear medicine departments. Between October 2008 and September 2019, 3343 men underwent F-choline PET/CT scans before receiving definitive treatments for a primary PCa or biochemical recurrence. Inclusion criteria were (1) histologically proven PCa (on surgical specimens or prostate biopsies from patients not treated surgically) and (2) availability of clinical and pathological data, including serum prostate specific antigen (PSA) level at the time of PET/CT scanning. RESULTS: F-choline PET/CT was performed in 545 cases (16.4%) for cancer staging and in 2798 (83.6%) for restaging purposes, and the result was positive in 540 (99.1%) for the former and 1993 (71.2%) for the latter. A positive PET/CT result was always associated with a high Gleason score (>7) and high PSA levels (P < 0.01). The percentage of patients with a PSA threshold less than 1.0 ng/mL for performing PET/CT was higher in the years 2014 to 2019 (n = 341, 25% of cases) than during the previous period (n = 148, 16%; in 2008-2013). When used for staging purposes, receiver operating characteristic analysis showed that PSA levels of 9.2, 16.4, and 16.6 ng/mL were the optimal cutoffs for distinguishing between positive and negative PET/CT findings for local disease, lymph node involvement, and metastasis, respectively. In the restaging setting, a PSA level of 1.27 ng/mL was the optimal cutoff for distinguishing between a positive and negative PET/CT scan. CONCLUSIONS: F-choline PET/CT can help identify early recurrences, even in the case of low PSA levels (<1 ng/mL). Our data suggest that important improvements have been made in the interpretation of F-choline images and in patient selection in the last 5 years.

Radiological Assessment of Paediatric Fungal Infections: A Pictorial Review With Focus on PET/MRI.

Paediatric invasive fungal infections have significantly increased over the past few decades, in particular among the immunocompromised population. Candida and Aspergillus spp. are still the most commonly isolated organisms. Image-based assessment of fungal infections can indeed be challenging especially in oncological patients where the differential diagnosis relative to other infections and neoplastic lesions cannot be often obvious. Therefore, the knowledge of the main radiological features associated with fungal infections is crucial to achieve an early correct diagnosis and address the most appropriate therapeutic approach. Thus, our aim was to review the main radiological features of paediatric fungal infections with particular focus on positron emission tomography/magnetic resonance imaging (PET/MRI), referring to the experience of our tertiary level hospital.

Role and cost-effectiveness of adrenal imaging and image-guided FNA cytology in the management of incidentally discovered adrenal tumours.

Incidentally discovered adrenal masses (incidentalomas) are relatively frequent and unsuspected incidentalomas (AI) of more than 1 cm in size may be found in 1-5% of patients who have undergone abdominal or chest computed tomography (CT)-scan for unrelated reasons. Once an AI is detected, the two major questions are whether the patient has biochemical evidence of adrenal hyperfunction, and whether the mass is an adrenal metastasis or a malignant adrenal tumour. In most cases (>90%) AI are non-functioning, with a low (<10%) risk of being malignant, and an estimated cumulative risk of malignant transformation of less than 1:1000. However, all patients with non-functioning AI usually undergo several imaging studies, but the impact of imaging techniques and image-guided fine-needle aspiration cytology (FNAC) on the cost-effectiveness in the management of patients is not well established. A single test for disease probabilities is not always more cost-effective than two-test approaches and it has been shown that the cumulative sensitivity and accuracy of both FNAC + magnetic resonance imaging (MRI) and FNAC + norcholesterol adrenal scintigraphy reach 100%, at a similar cost-to-accuracy ratio (7.5 vs. 7.0), whilst the strategy CT-scan + MRI together is less sensitive at a lower cost-to-accuracy ratio. In conclusion, the significance of AI, as well as the optimal management approach to treatment, is still under discussion. However, image-guided FNAC in conjunction with MRI as the exclusive imaging test has the major role and cost-effectiveness in the management of patients with AL, and should be considered the strategy of choice in distinguishing between benign and malignant non-functioning adrenal masses of more than 2 cm in diameter.