Correlation between rCBV Delineation Similarity and Overall Survival in a Prospective Cohort of High-Grade Gliomas Patients: The Hidden Value of Multimodal MRI?

PURPOSE: The accuracy of target delineation in radiation treatment planning of high-grade gliomas (HGGs) is crucial to achieve high tumor control, while minimizing treatment-related toxicity. Magnetic resonance imaging (MRI) represents the standard imaging modality for delineation of gliomas with inherent limitations in accurately determining the microscopic extent of tumors. The purpose of this study was to assess the survival impact of multi-observer delineation variability of multiparametric MRI (mpMRI) and [18F]-FET PET/CT. MATERIALS AND METHODS: Thirty prospectively included patients with histologically confirmed HGGs underwent a PET/CT and mpMRI including diffusion-weighted imaging (DWI: b0, b1000, ADC), contrast-enhanced T1-weighted imaging (T1-Gado), T2-weighted fluid-attenuated inversion recovery (T2Flair), and perfusion-weighted imaging with computation of relative cerebral blood volume (rCBV) and K2 maps. Nine radiation oncologists delineated the PET/CT and MRI sequences. Spatial similarity (Dice similarity coefficient: DSC) was calculated between the readers for each sequence. Impact of the DSC on progression-free survival (PFS) and overall survival (OS) was assessed using Kaplan-Meier curves and the log-rank test. RESULTS: The highest DSC mean values were reached for morphological sequences, ranging from 0.71 +/- 0.18 to 0.84 +/- 0.09 for T2Flair and T1Gado, respectively, while metabolic volumes defined by PET/CT achieved a mean DSC of 0.75 +/- 0.11. rCBV variability (mean DSC0.32 +/- 0.20) significantly impacted PFS (p = 0.02) and OS (p = 0.002). CONCLUSIONS: Our data suggest that the T1-Gado and T2Flair sequences were the most reproducible sequences, followed by PET/CT. Reproducibility for functional sequences was low, but rCBV inter-reader similarity significantly impacted PFS and OS.

Mismatch Between Brain MRIs and 18 F-DOPA PET/CT : Impact on the Management of a Long Survivor With EGFR-Mutated Lung Adenocarcinoma.

ABSTRACT: After receiving erlotinib for 4 years, a man with advanced lung adenocarcinoma was treated with stereotactic radiotherapy for a left cerebellar brain metastasis. Local relapse of the metastasis was suspected 14 months after and confirmed on 18 F-DOPA PET. Three additional uptakes were described with no unequivocal MRI pathological signal. A second radiotherapy course was delivered. One year later, isolated local recurrence was suspected on a 3 T MRI, with a suspicious 18 F-DOPA uptake. Five additional 18 F-DOPA uptakes were described among which one increased between the 2 PETs. Because of these MRI/PET mismatches, a switch from erlotinib to osimertinib was preferred over surgery.

Radiotherapy Target Volume Definition in Newly Diagnosed High-Grade Glioma Using 18F-FET PET Imaging and Multiparametric MRI: An Inter Observer Agreement Study.

Background: The aim of this prospective monocentric study was to assess the inter-observer agreement for tumor volume delineations by multiparametric MRI and 18-F-FET-PET/CT in newly diagnosed, untreated high-grade glioma (HGG) patients. Methods: Thirty patients HGG underwent O-(2-[18F]-fluoroethyl)-l-tyrosine(18F-FET) positron emission tomography (PET), and multiparametric MRI with computation of rCBV map and K2 map. Three nuclear physicians and three radiologists with different levels of experience delineated the 18-F-FET-PET/CT and 6 MRI sequences, respectively. Spatial similarity (Dice and Jaccard: DSC and JSC) and overlap (Overlap: OV) coefficients were calculated between the readers for each sequence. Results: DSC, JSC, and OV were high for 18F-FET PET/CT, T1-GD, and T2-FLAIR (>0.67). The Spearman correlation coefficient between readers was ≥0.6 for these sequences. Cross-comparison of similarity and overlap parameters showed significant differences for DSC and JSC between 18F-FET PET/CT and T2-FLAIR and for JSC between 18F-FET PET/CT and T1-GD with higher values for 18F-FET PET/CT. No significant difference was found between T1-GD and T2-FLAIR. rCBV, K2, b1000, and ADC showed correlation coefficients between readers <0.6. Conclusion: The interobserver agreements for tumor volume delineations were high for 18-F-FET-PET/CT, T1-GD, and T2-FLAIR. The DWI (b1000, ADC), rCBV, and K2-based sequences, as performed, did not seem sufficiently reproducible to be used in daily practice.

Systemic Artery to Pulmonary Artery Shunt Mimicking Acute Pulmonary Embolism, Unmasked by a Multimodality Imaging Approach.

In this report, we describe the functional imaging findings of systemic artery to pulmonary artery shunt in V/Q SPECT CT imaging. A 63-year-old man with small-cell lung cancer underwent CT pulmonary angiography (CTPA) for suspected acute pulmonary embolism (PE). The CTPA showed an isolated segmental filling defect in the right lower lobe, which was initially interpreted as positive for PE but was actually the consequence of a systemic artery to pulmonary artery shunt due to the recruitment of the bronchial arterial network by the adjacent tumor. A V/Q SPECT/CT scan was also performed, demonstrating a matched perfusion/ventilation defect in the right lower lobe.

Hotspot on 18F-FET PET/CT to Predict Aggressive Tumor Areas for Radiotherapy Dose Escalation Guiding in High-Grade Glioma.

The standard therapy strategy for high-grade glioma (HGG) is based on the maximal surgery followed by radio-chemotherapy (RT-CT) with insufficient control of the disease. Recurrences are mainly localized in the radiation field, suggesting an interest in radiotherapy dose escalation to better control the disease locally. We aimed to identify a similarity between the areas of high uptake on O-(2-[18F]-fluoroethyl)-L-tyrosine (FET) positron emission tomography/computed tomography (PET) before RT-CT, the residual tumor on post-therapy NADIR magnetic resonance imaging (MRI) and the area of recurrence on MRI. This is an ancillary study from the IMAGG prospective trial assessing the interest of FET PET imaging in RT target volume definition of HGG. We included patients with diagnoses of HGG obtained by biopsy or tumor resection. These patients underwent FET PET and brain MRIs, both after diagnosis and before RT-CT. The follow-up consisted of sequential brain MRIs performed every 3 months until recurrence. Tumor delineation on the initial MRI 1 (GTV 1), post-RT-CT NADIR MRI 2 (GTV 2), and progression MRI 3 (GTV 3) were performed semi-automatically and manually adjusted by a neuroradiologist specialist in neuro-oncology. GTV 2 and GTV 3 were then co-registered on FET PET data. Tumor volumes on FET PET (MTV) were delineated using a tumor to background ratio (TBR) ≥ 1.6 and different % SUVmax PET thresholds. Spatial similarity between different volumes was performed using the dice (DICE), Jaccard (JSC), and overlap fraction (OV) indices and compared together in the biopsy or partial surgery group (G1) and the total or subtotal surgery group (G2). Another overlap index (OV') was calculated to determine the threshold with the highest probability of being included in the residual volume after RT-CT on MRI 2 and in MRI 3 (called "hotspot"). A total of 23 patients were included, of whom 22% (n = 5) did not have a NADIR MRI 2 due to a disease progression diagnosed on the first post-RT-CT MRI evaluation. Among the 18 patients who underwent a NADIR MRI 2, the average residual tumor was approximately 71.6% of the GTV 1. A total of 22% of patients (5/23) showed an increase in GTV 2 without diagnosis of true progression by the multidisciplinary team (MDT). Spatial similarity between MTV and GTV 2 and between MTV and GTV 3 were higher using a TBR ≥ 1.6 threshold. These indices were significantly better in the G1 group than the G2 group. In the FET hotspot analysis, the best similarity (good agreement) with GTV 2 was found in the G1 group using a 90% SUVmax delineation method and showed a trend of statistical difference with those (poor agreement) in the G2 group (OV' = 0.67 vs. 0.38, respectively, p = 0.068); whereas the best similarity (good agreement) with GTV 3 was found in the G1 group using a 80% SUVmax delineation method and was significantly higher than those (poor agreement) in the G2 group (OV'= 0.72 vs. 0.35, respectively, p = 0.014). These results showed modest spatial similarity indices between MTV, GTV 2, and GTV 3 of HGG. Nevertheless, the results were significantly improved in patients who underwent only biopsy or partial surgery. TBR ≥ 1.6 and 80-90% SUVmax FET delineation methods showing a good agreement in the hotspot concept for targeting standard dose and radiation boost. These findings need to be tested in a larger randomized prospective study.

18F-FET PET/CT in Early Subventricular Zone Recurrence of Adult Glioblastoma.

ABSTRACT: Glioma stem cells (GSCs) are the source of tumor recurrence in glioblastoma and are capable of whole tumor regeneration once the treatment has concluded. Compelling evidence from the last decade suggests that GSC may arise from neural stem cells residing in the adult subventricular zone (SVZ). We report the findings of an 18F-FET PET/CT showing pathological uptake in SVZ with a tumor-background ratio of greater than 1.6, giving evidence for glioblastoma recurrence. This case highlights the particular attention to be paid to the SVZ given the possible development of GSC.

Four-dimensional computed tomography angiography analysis of internal carotid arteries opacification at the skull base to detect delayed cerebral ischemia: a feasibility study.

PURPOSE: Delayed cerebral ischemia represents a significant cause of poor functional outcome for patients with vasospasm after subarachnoid hemorrhage. We investigated whether delayed cerebral ischemia could be detected by the arterial opacification of internal carotid artery at the level of the skull base. METHODS: In this exploratory, nested retrospective cohort diagnostic accuracy study, patients with clinical and/or transcranial Doppler suspicion of vasospasm who underwent four-dimensional computed tomography angiography were included. They were split into two groups for the main endpoint analysis, according to the actually adopted morphological (cerebral infarction) and clinical criteria (neurologic deterioration) of delayed cerebral ischemia. Opacification with a temporal resolution of 0.15 s of both internal carotid arteries at the skull base level was obtained through a semi-automated segmentation method based on skeletonization, and analyzed by a wavelet transform (rbio2.2, level 1). The results obtained by k-means clustering were analyzed with regard to the state of delayed cerebral infarction. RESULTS: Over ten patients included and analyzed, five patients presented a delayed cerebral ischemia, two of them in both side. The semi-automated processing and analysis clustered two different types of opacification curves. The obtaining of a nonlinear opacification pattern was associated (p < 0.001) with delayed cerebral ischemia. CONCLUSIONS: The analysis of arterial opacification of internal carotid arteries at skull base by the proposed processing is feasible and leads to cluster two types of opacification that may help to early detect and prevent delayed cerebral ischemia, in particularly when examinations are artifacted by aneurysm treatment materials.

Radiotherapy target volume definition in newly diagnosed high grade glioma using 18F-FET PET imaging and multiparametric perfusion MRI: A prospective study (IMAGG).

PURPOSE: The aim of this study was to prospectively investigate tumor volume delineation by amino acid PET and multiparametric perfusion magnetic resonance imaging (MRI) in patients with newly diagnosed, untreated high grade glioma (HGG). MATERIALS AND METHODS: Thirty patients with histologically confirmed HGG underwent O-(2-[18F]-fluoroethyl)-l-tyrosine (18F-FET) positron emission tomography (PET), conventional Magnetic Resonance Imaging (MRI) as contrast-enhanced (CE) and fluid-attenuated inversion recovery (FLAIR) and multiparametric MRI as relative cerebral blood volume (rCBV) and permeability estimation map (K2). Areas of MRI volumes were semi-automatically segmented. The percentage overlap volumes, Dice and Jaccard spatial similarity coefficients (OV, DSC, JSC) were calculated. RESULTS: The 18F-FET tumor volume was significantly larger than the CE volume (median 43.5 mL (2.5-124.9) vs. 23.8 mL (1.4-80.3), p = 0.005). The OV between 18F-FET uptake and CE volume was low (median OV 0.59 (0.10-1)), as well as spatial similarity (median DSC 0.52 (0.07-0.78); median JSC 0.35 (0.03-0.64)). Twenty-five patients demonstrated both rCBV and CE on MRI: The median rCBV tumor volume was significantly smaller than the median CE volume (p < 0.001). The OV was high (median 0.83 (0.54-1)), but the spatial similarity was low (median DSC 0.45 (0.04-0.83); median JSC 0.29 (0.07-0.71)). Twenty-eight patients demonstrated both K2 and CE on MRI. The median K2 tumor volume was not significantly larger than the median CE volume. The OV was high (median OV 0.90 (0.61-1)), and the spatial similarity was moderate (median DSC 0.75 (0.01-0.83); median JSC 0.60 (0.11-0.89)). CONCLUSION: We demonstrated that multiparametric perfusion MRI volumes (rCBV, K2) were highly correlated with CE T1 gadolinium volumes whereas 18F-FET PET provided complementary information, suggesting that the metabolically active tumor volume in patients with newly diagnosed untreated HGG is critically underestimated by contrast enhanced MRI. 18F-FET PET imaging may help to improve target volume delineation accuracy for radiotherapy planning.

Gallium-68 Ventilation/Perfusion PET-CT and CT Pulmonary Angiography for Pulmonary Embolism Diagnosis: An Interobserver Agreement Study.

Objectives: 68Ga Ventilation/Perfusion V/Q PET-CT is a promising imaging tool for pulmonary embolism diagnosis. However, no study has verified whether the interpretation is reproducible between different observers. The aim of this study was to assess the interobserver agreement in the interpretation of V/Q PET-CT for the diagnosis of acute PE, and to compare it to the interobserver agreement of CTPA interpretation. Methods: Twenty-four cancer patients with suspected acute PE underwent V/Q PET-CT and CTPA within 24 h as part of a prospective pilot study evaluating V/Q PET-CT for the management of patients with suspected PE. V/Q PET-CT and CTPA scans were reassessed independently by four nuclear medicine physicians and four radiologists, respectively. Physicians had different levels of expertise in reading V/Q scintigraphy and CTPA. Interpretation was blinded to the initial interpretation and any clinical information or imaging test result. For each modality, results were reported on a binary fashion. V/Q PET/CT scans were read as positive if there was at least one segmental or two subsegmental mismatched perfusion defects. CTPA scans were interpreted as positive if there was a constant intraluminal filling defect. Interobserver agreement was assessed by calculating kappa (κ) coefficients. Results: Out of the 24 V/Q PET-CT scans, the diagnostic conclusion was concordantly negative in 22 patients and concordantly positive in one patient. The remaining scan was interpreted as positive by one reader and negative by three readers. Out of the 24 CTPA scans, the diagnostic conclusion was concordantly negative in 16 and concordantly positive in one. Out of the seven remaining scans, PE was reported by one reader in four cases, by two readers in two cases, by three readers in one case. Most of discordant results on CTPA were related to clots reported on subsegmental arteries. Mean kappa coefficient was 0.79 for V/Q PET-CT interpretation and 0.39 for CTPA interpretation. Conclusions: Interobserver agreement in the interpretation of V/Q PET-CT for PE diagnosis was substantial (kappa 0.79) in a population with a low prevalence of significant PE. Agreement was lower with CTPA, mainly as a result of discrepancies at the level of the subsegmental arteries.

Volume variation may be a relevant metric in the study of aneurysm pulsatility: a study using ECG-gated 4D-CTA (PULSAN).

​BACKGROUND AND PURPOSE: Intracranial aneurysms are a frequently occurring disease, with an estimated prevalence of 2-5% in the general population. They usually remain silent until rupture occurs, with a mortality rate of 35-50% and a high rate of morbidity, including long-term disability. However, preventative treatments have their own risk of complications and morbi-mortality rates, including stroke and hemorrhage. ECG-gated four-dimensional CT angiography (4D-CTA) allows the acquisition of time-resolved three-dimensional reconstructions. The aim of our study was to evaluate different intracranial aneurysm metrics over the cardiac cycle using ECG-gated 4D-CTA. ​MATERIALS AND METHODS: ECG-gated 4D-CTA datasets were acquired in patients presenting with intracranial aneurysms. Seven aneurysm metrics, including aneurysm height, aneurysm length, ostium width, aspect ratio, ostium area, volume, and volume-to-ostium ratio, were analysed over different cardiac phases. Intra-reader agreement, inter-reader agreement, and inter-cycle agreement were calculated through the intraclass correlation coefficient. ​RESULTS: Twenty-one aneurysms from 11 patients were considered for inclusion. Post-processing failed for three aneurysms, and 18 aneurysms were finally analysed. There was good intra-reader agreement for each metric (ICC >0.9). Agreements among three consecutive cardiac cycles were calculated for six aneurysms and were especially good for the volume metric (ICC >0.9). Volume variation appears to be the most relevant metric and seems especially perceptible for aneurysms larger than 5 mm. ​CONCLUSIONS: Quantification of aneurysm volume changes during the cardiac cycle seems quantitatively possible and reproducible, especially for aneurysms larger than 5 mm. Further studies need to be conducted to validate this parameter for intracranial aneurysm assessment.