Focal 18 F-FDG uptake predicts progression of pre-invasive squamous bronchial lesions to invasive cancers.

INTRODUCTION: Pre-invasive squamous lesions of the central airways can progress into invasive lung cancers. Identifying these high-risk patients could enable detection of invasive lung cancers at an early stage. In this study, we investigated the value of 18 F-fluorodeoxyglucose (18 F-FDG) positron emission tomography (PET) scans in predicting progression in patients with pre-invasive squamous endobronchial lesions. METHODS: In this retrospective study, patients with pre-invasive endobronchial lesions, who underwent an 18 F-FDG PET scan at the VU University Medical Center Amsterdam, between January 2000 and December 2016, were included. Autofluorescence bronchoscopy (AFB) was used for tissue sampling and was repeated every 3 months. The minimum and median follow-up was 3 and 46.5 months. Study endpoints were the occurrence of biopsy proven invasive carcinoma, time-to-progression and overall survival (OS). RESULTS: A total number of 40 of 225 patients met the inclusion criteria of which 17 (42.5%) patients had a positive baseline 18 F-FDG PET scan. A total of 13 of 17 (76.5%) developed invasive lung carcinoma during follow-up, with a median time to progression of 5.0 months (range, 3.0-25.0). In 23 (57.5%) patients with a negative 18 F-FDG PET scan at baseline, 6 (26%) developed lung cancer, with a median time to progression of 34.0 months (range, 14.0-42.0 months, p < 0.002). With a median OS of 56.0 months (range, 9.0-60.0 months) versus 49.0 months (range, 6.0-60.0 months) (p = 0.876) for the 18 F-FDG PET positive and negative groups, respectively. CONCLUSIONS: Patients with pre-invasive endobronchial squamous lesions and a positive baseline 18 F-FDG PET scan were at high-risk for developing lung carcinoma, highlighting that this patient group requires early radical treatment.

The Additional Value of Ultrafast DCE-MRI to DWI-MRI and 18F-FDG-PET to Detect Occult Primary Head and Neck Squamous Cell Carcinoma.

To evaluate diagnostic accuracy of qualitative analysis and interobserver agreement of single ultrafast-DCE, DWI or 18F-FDG-PET and the combination of modalities for the detection of unknown primary tumor (UPT) in patients presenting with cervical lymph node metastasis from squamous cell carcinoma (SCC). Between 2014-2019, patients with histologically proven cervical lymph node metastasis of UPT SCC were prospectively included and underwent DWI, ultrafast-DCE, and 18F-FDG-PET/CT. Qualitative assessment was performed by two observers per modality. Interobserver agreement was calculated using the proportion specific agreement. Diagnostic accuracy of combined use of DWI, ultrafast-DCE and 18F-FDG-PET/CT was assessed. Twenty-nine patients were included (20 males. [68%], median age 60 years). Nine (31%) primary tumors remained occult. Ultrafast-DCE added reader confidence for suspicious locations (one additional true positive (5%), 2 decisive true malignant (10%). The per-location analysis showed highest specific positive agreement for ultrafast-DCE (77.6%). The per-location rating showed highest sensitivity (95%, 95%CI = 75.1-99.9, YI = 0.814) when either one of all modalities was scored positive, and 97.4% (95%CI = 93.5-99.3, YI = 0.774) specificity when co-detected on all. The per-patient analysis showed highest sensitivity (100%) for 18F-FDG-PET/CT (YI = 0.222) and either DWI or PET (YI = 0.111). Despite highest trends, no significant differences were found. The per-patient analysis showed highest specific positive agreement when co-detected on all modalities (55.6%, 95%CI = 21.2-86.3, YI = 0.456). Ultrafast-DCE showed potential to improve detection of unknown primary tumors in addition to DWI and 18F-FDG-PET/CT in patients with cervical squamous cell carcinoma lymph node metastasis. The combined use of ultrafast-DCE, DWI and 18F-FDG-PET/CT yielded highest sensitivity.

Should vascular wall 18F-FDG uptake be adjusted for the extent of atherosclerotic burden?

Vascular wall 18F-FDG uptake is often used as a surrogate marker of atherosclerotic plaque inflammation. A potential caveat is that vascular wall 18F-FDG uptake is higher simply because more atherosclerosis is present. To determine if the degree of inflammation is high or low relative to the extent of atherosclerosis, vascular wall 18F-FDG uptake may require statistical adjustment for a non-inflammatory marker reflecting the extent of atherosclerosis, e.g. calcification. Adjustments is probably needed if (1) vascular wall 18F-FDG uptake correlates sufficiently strongly with arterial calcification and (2) adjustment for extent of calcification affects determinants of vascular 18F-FDG uptake. This study addresses these questions. 18F-FDG PET/low-dose-CT scans of 99 patients were used. Cardiovascular risk factors were assessed and PET/CT scans were analysed for standardized 18F-FDG uptake values and calcification. ANOVA was used to establish the association between vascular 18F-FDG uptake and calcification. Multiple linear regression (with and without calcification as independent variable) was used to show whether determinants of vascular 18F-FDG uptake were affected by the degree of calcification. 18F-FDG uptake was related to increased calcification in the aortic arch, descending and abdominal aorta. However, 18F-FDG uptake showed considerable overlap between categories of calcification. Age and body mass index were main determinants of vascular 18F-FDG uptake. In multiple regression analyses, most standardized beta coefficients of these determinants were not affected by adjustment for the degree of calcification. Although vascular 18F-FDG uptake is related to total atherosclerotic burden, as reflected by vascular calcification, the association is weak and unlikely to affect the identification of determinants of atherosclerotic inflammation implicating no need for adjustment in future studies.

Tumor Atelectasis Gives Rise to a Solid Appearance in Pulmonary Adenocarcinomas on High-Resolution Computed Tomography.

INTRODUCTION: Ground-glass opacities in a high-resolution computed tomography (HR-CT) scan correlate, if malignant, with adenocarcinoma in situ. The solid appearance in the HR-CT is often considered indicative of an invasive component. This study aims to compare the radiologic features revealed in the HR-CT and the histologic features of primary adenocarcinomas in resection specimens to find the presence of tumor atelectasis in ground-glass nodules (GGNs) and part-solid and solid nodules. METHODS: HR-CT imaging was evaluated, and lung nodules were classified as GGNs, part-solid nodules, and solid nodules, whereas adenocarcinomas were classified according to WHO classification. Lepidic growth pattern with collapse was considered if there was reduction of air in the histologic section with maintained pulmonary architecture (without signs of pleural or vascular invasion). RESULTS: Radiologic and histologic features were compared in 47 lesions of 41 patients. The number of GGN, part-solid, and solid nodules were two, eight, and 37, respectively. Lepidic growth pattern with collapse was observed in both GGN, seven of the eight part-solid (88%) and 24 of the 37 solid (65%) lesions. Remarkably, more than 50% of the adenocarcinomas with a solid appearance in HR-CT imaging had a preexisting pulmonary architecture with adenocarcinoma with a predominant lepidic growth pattern. In these cases, the solid component can be explained by tumor-related collapse in vivo (tumor atelectasis on radiologic examination). CONCLUSIONS: Tumor atelectasis is a frequent finding in pulmonary adenocarcinomas and may beside a ground glass opacity also result in a solid appearance in HR-CT imaging. A solid appearance on HR-CT cannot be attributed to invasion alone, as has been the assumption until now.

Variability in quantitative analysis of atherosclerotic plaque inflammation using 18F-FDG PET/CT.

BACKGROUND: 18F-FDG-PET(/CT) is increasingly used in studies aiming at quantifying atherosclerotic plaque inflammation. Considerable methodological variability exists. The effect of data acquisition and image analysis parameters on quantitative uptake measures, such as standardized uptake value (SUV) and target-to-background ratio (TBR) has not been investigated extensively. OBJECTIVE: The goal of this study was to explore the effect of several data acquisition and image analysis parameters on quantification of vascular wall 18F-FDG uptake measures, in order to increase awareness of potential variability. METHODS: Three whole-body emission scans and a low-dose CT scan were acquired 38, 60 and 90 minutes after injection of 18F-FDG in six rheumatoid arthritis patients with high cardiovascular risk profiles.Data acquisition (1 and 2) and image analysis (3, 4 and 5) parameters comprised:1. 18F-FDG uptake time, 2. SUV normalisation, 3. drawing regions/volumes of interest (ROI's/VOI's) according to: a. hot-spot (HS), b. whole-segment (WS) and c. most-diseased segment (MDS), 4. Background activity, 5. Image matrix/voxel size.Intraclass correlation coefficients (ICC's) and Bland Altman plots were used to assess agreement between these techniques and between observers. A linear mixed model was used to determine the association between uptake time and continuous outcome variables. RESULTS: 1. Significantly higher TBRmax values were found at 90 minutes (1,57 95%CI 1,35-1,80) compared to 38 minutes (1,30 95%CI 1,21-1,39) (P = 0,024) 2. Normalising SUV for BW, LBM and BSA significantly influences average SUVmax (2,25 (±0,60) vs 1,67 (±0,37) vs 0,058 (±0,013)). 3. Intraclass correlation coefficients were high in all vascular segments when SUVmax HS was compared to SUVmax WS. SUVmax HS was consistently higher than SUVmax MDS in all vascular segments. 4. Blood pool activity significantly decreases in all (venous and arterial) segments over time, but does not differ between segments. 5. Image matrix/voxel size does not influence SUVmax. CONCLUSION: Quantitative measures of vascular wall 18F-FDG uptake are affected mainly by changes in data acquisition parameters. Standardization of methodology needs to be considered when studying atherosclerosis and/or vasculitis.

Cost-effectiveness of response evaluation after chemoradiation in patients with advanced oropharyngeal cancer using 18F-FDG-PET-CT and/or diffusion-weighted MRI.

BACKGROUND: Considerable variation exists in diagnostic tests used for local response evaluation after chemoradiation in patients with advanced oropharyngeal cancer. The yield of invasive examination under general anesthesia (EUA) with biopsies in all patients is low and it may induce substantial morbidity. We explored four response evaluation strategies to detect local residual disease in terms of diagnostic accuracy and cost-effectiveness. METHODS: We built a decision-analytic model using trial data of forty-six patients and scientific literature. We estimated for four strategies the proportion of correct diagnoses, costs concerning diagnostic instruments and the proportion of unnecessary EUA indications. Besides a reference strategy, i.e. EUA for all patients, we considered three imaging strategies consisting of 18FDG-PET-CT, diffusion-weighted MRI (DW-MRI), or both 18FDG-PET-CT and DW-MRI followed by EUA after a positive test. The impact of uncertainty was assessed in sensitivity analyses. RESULTS: The EUA strategy led to 96% correct diagnoses. Expected costs were €468 per patient whereas 89% of EUA indications were unnecessary. The DW-MRI strategy was the least costly strategy, but also led to the lowest proportion of correct diagnoses, i.e. 93%. The PET-CT strategy and combined imaging strategy were dominated by the EUA strategy due to respectively a smaller or equal proportion of correct diagnoses, at higher costs. However, the combination of PET-CT and DW-MRI had the highest sensitivity. All imaging strategies considerably reduced (unnecessary) EUA indications and its associated burden compared to the EUA strategy. CONCLUSIONS: Because the combined PET-CT and DW-MRI strategy costs only an additional €927 per patient, it is preferred over immediate EUA since it reaches the same diagnostic accuracy in detecting local residual disease while leading to substantially less unnecessary EUA indications. However, if healthcare resources are limited, DW-MRI is the strategy of choice because of lower costs while still providing a large reduction in unnecessary EUA indications.

Altered GABAA receptor density and unaltered blood-brain barrier [11C]flumazenil transport in drug-resistant epilepsy patients with mesial temporal sclerosis.

Studies in rodents suggest that flumazenil is a P-glycoprotein substrate at the blood-brain barrier. This study aimed to assess whether [11C]flumazenil is a P-glycoprotein substrate in humans and to what extent increased P-glycoprotein function in epilepsy may confound interpretation of clinical [11C]flumazenil studies used to assess gamma-aminobutyric acid A receptors. Nine drug-resistant patients with epilepsy and mesial temporal sclerosis were scanned twice using [11C]flumazenil before and after partial P-glycoprotein blockade with tariquidar. Volume of distribution, nondisplaceable binding potential, and the ratio of rate constants of [11C]flumazenil transport across the blood-brain barrier (K1/k2) were derived for whole brain and several regions. All parameters were compared between pre- and post-tariquidar scans. Regional results were compared between mesial temporal sclerosis and contralateral sides. Tariquidar significantly increased global K1/k2 (+23%) and volume of distribution (+10%), but not nondisplaceable binding potential. At the mesial temporal sclerosis side volume of distribution and nondisplaceable binding potential were lower in hippocampus (both ∼-19%) and amygdala (both ∼-16%), but K1/k2 did not differ, suggesting that only regional gamma-aminobutyric acid A receptor density is altered in epilepsy. In conclusion, although [11C]flumazenil appears to be a (weak) P-glycoprotein substrate in humans, this does not seem to affect its role as a tracer for assessing gamma-aminobutyric acid A receptor density.

Radiofrequency Ablation to Improve Survival After Conversion Chemotherapy for Colorectal Liver Metastases.

INTRODUCTION: Systemic chemotherapy is able to convert colorectal liver metastases (CRLM) that are initially unsuitable for local treatment into locally treatable disease. Surgical resection further improves survival in these patients. Our aim was to evaluate disease-free survival (DFS), overall survival, and morbidity for patients with CRLM treated with RFA following effective downstaging by chemotherapy, and to identify factors associated with recurrence and survival. MATERIALS AND METHODS: Included patients had liver-dominant CRLM initially unsuitable for local treatment but eligible for RFA or RFA with resection after downstaging by systemic chemotherapy. Chemotherapeutic regimens consisted predominantly of CapOx, with or without bevacizumab. Follow-up was conducted with PET-CT or thoraco-pelvic CT. RESULTS: Fifty-one patients had a total of 325 CRLM (median = 7). Following chemotherapy, 183 lesions were still visible on CT (median = 3). Twenty-six patients were treated with RFA combined with resection. During surgery, 309 CRLM were retrieved on intraoperative ultrasound (median = 5). Median survival was 49 months and was associated with extrahepatic disease at time of presentation and recurrences after treatment. Estimated cumulative survival at 1, 3 and 4 years was 90, 63 and 45 %, respectively. Median DFS was 6 months. Twelve patients remained free of recurrence after a mean follow-up of 32.6 months. CONCLUSION: RFA of CRLM after conversion chemotherapy provides potential local control and a good overall survival. To prevent undertreatment, the involvement of a multidisciplinary team in follow-up imaging and assessment of local treatment possibilities after palliative chemotherapy for liver-dominant CRLM should always be considered.

Effectiveness of an (18)F-FDG-PET based strategy to optimize the diagnostic trajectory of suspected recurrent laryngeal carcinoma after radiotherapy: The RELAPS multicenter randomized trial.

PURPOSE: The purpose of this study is to evaluate the efficacy of (18)F-FDG-PET as first-line diagnostic investigation, prior to performing a direct laryngoscopy with biopsy under general anesthesia, in patients suspected of recurrent laryngeal carcinoma after radiotherapy. PATIENTS AND METHODS: 150 patients suspected of recurrent T2-4 laryngeal carcinoma at least two months after prior (chemo)radiotherapy with curative intent for resectable disease were randomized to direct laryngoscopy (CWU: conventional workup strategy) or to (18)F-FDG-PET only followed by direct laryngoscopy if PET was assessed 'positive' or 'equivocal' (PWU: PET based workup strategy), to compare the effectiveness of these strategies. Primary endpoint was the number of indications for direct laryngoscopies classified as unnecessary based on absence of recurrence, both on direct laryngoscopy and on six month follow up. Safety endpoints comprised resectability of recurrent lesions and completeness of surgical margins following salvage laryngectomy. RESULTS: Intention-to-treat analyses were performed on all randomized patients (CWU: n=74, PWU: n=76). Tumor recurrence was similar in both groups: 45 patients (30%; 21 CWU, 24 PWU) within six months. In 53 patients in the CWU arm (72%, 95% CI: 60-81) unnecessary direct laryngoscopies were performed compared to 22 in the PWU arm (29%, 95% CI: 19-40) (p<0·0001). The percentage of salvage laryngectomies (resectability) and positive surgical margins were similar between CWU and PWU (81%, 63% respectively, p=0·17, and 29%, 7%, respectively, p=0.20). The prevalence of the combination of local unresectability and positive margins is in the CWU group 24% and in the PWU group 8%. No difference (p=0.32) in disease specific survival between both groups was found. CONCLUSION: In patients with suspected laryngeal carcinoma after radiotherapy, PET as the first diagnostic procedure can reduce the need for direct laryngoscopy by more than 50% without jeopardizing quality of treatment.

Colorectal liver metastatic disease: efficacy of irreversible electroporation--a single-arm phase II clinical trial (COLDFIRE-2 trial).

BACKGROUND: Irreversible electroporation (IRE) is a novel image-guided tumor ablation technique that has shown promise for the ablation of lesions in proximity to vital structures such as blood vessels and bile ducts. The primary aim of the COLDFIRE-2 trial is to investigate the efficacy of IRE for unresectable, centrally located colorectal liver metastases (CRLM). Secondary outcomes are safety, technical success, and the accuracy of contrast-enhanced (ce)CT and (18)F-FDG PET-CT in the detection of local tumor progression (LTP). METHODS/DESIGN: In this single-arm, multicenter phase II clinical trial, twenty-nine patients with (18)F-FDG PET-avid CRLM ≤ 3,5 cm will be prospectively included to undergo IRE of the respective lesion. All lesions must be unresectable and unsuitable for thermal ablation due to vicinity of vital structures. Technical success is based on ceMRI one day post-IRE. All complications related to the IRE procedure are registered. Follow-up consists of (18)F-FDG PET-CT and 4-phase liver CT at 3-monthly intervals during the first year of follow-up. Treatment efficacy is defined as the percentage of tumors successfully eradicated 12 months after the initial IRE procedure based on clinical follow-up using both imaging modalities, tumor marker and (if available) histopathology. To determine the accuracy of (18)F-FDG PET-CT and ceCT, both imaging modalities will be individually scored by two reviewers that are blinded for the final oncologic outcome. DISCUSSION: To date, patients with a central CRLM unsuitable for resection or thermal ablation have no curative treatment option and are given palliative chemotherapy. For these patients, IRE may prove a life-saving treatment option. The results of the proposed trial may represent an important step towards the implementation of IRE for central liver tumors in the clinical setting. TRIAL REGISTRATION NUMBER: NCT02082782.

Response evaluation after chemoradiotherapy for advanced nodal disease in head and neck cancer using diffusion-weighted MRI and 18F-FDG-PET-CT.

OBJECTIVES: Evaluation of accuracy and interobserver variation of diffusion-weighted magnetic resonance imaging (DW-MRI) and 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDGPET-CT) to detect residual lymph node metastases after chemoradiotherapy (CRT) in advanced staged head and neck squamous cell carcinoma (HNSCC). MATERIALS AND METHODS: Retrospectively, routinely performed DW-MRI (n=73) and 18F-FDG-PET-CT (n=58) 3months after CRT in HNSCC-patients with advanced nodal disease (N2-N3) were assessed by two radiologists and two nuclear medicine physicians (individually and in consensus). Imaging was scored dichotomously and on a five-point Likert scale. We also explored different scenarios for the potential added value of DW-MRI to PET-CT using the consensus Likert scale. Histopathology and a follow-up of 9months after CRT served as reference standard. RESULTS: Five patients (7%) had residual regional disease. DW-MRI showed a sensitivity of 60% and a specificity of 93%, vs. 100% and 84% for PET-CT, respectively. DW-MRI and PET-CT observers had 'moderate' and 'substantial' interobserver agreement (κ=0.58 and κ=0.64, respectively) with the dichotomous system. The combination of PET-CT and DW-MRI showed a sensitivity of 100% and a specificity of 95%. CONCLUSION: The high sensitivity of PET-CT authorizes a neck dissection in all patients with a positive test result and the high specificity of DW-MRI justifies avoidance of invasive neck dissections if the test is negative. Interobserver agreement varied as a function of test positivity criteria. Adding DW-MRI to PET-CT seemed to increase the specificity of PET-CT alone, thereby ensuring that less patients are exposed to unnecessary neck dissections.

Diffusion-weighted EPI- and HASTE-MRI and 18F-FDG-PET-CT early during chemoradiotherapy in advanced head and neck cancer.

MAIN PROBLEM: Diffusion-weighted MRI (DW-MRI) has potential to predict chemoradiotherapy (CRT) response in head and neck squamous cell carcinoma (HNSCC) and is generally performed using echo-planar imaging (EPI). However, EPI-DWI is susceptible to geometric distortions. Half-fourier acquisition single-shot turbo spin-echo (HASTE)-DWI may be an alternative. This prospective pilot study evaluates the potential predictive value of EPI- and HASTE-DWI and 18F-fluorodeoxyglucose PET-CT (18F-FDG-PET-CT) early during CRT for locoregional outcome in HNSCC. METHODS: Eight patients with advanced HNSCC (7 primary tumors and 25 nodal metastases) scheduled for CRT, underwent DW-MRI (using both EPI- and HASTE-DWI) and 18F-FDG-PET(-CT) pretreatment, early during treatment and three months after treatment. Median follow-up time was 38 months. RESULTS: No local recurrences were detected during follow-up. Median Apparent Diffusion Coefficient (ADC)EPI-values in primary tumors increased from 77×10(-5) mm(2)/s pretreatment, to 113×10(-5) mm(2)/s during treatment (P=0.02), whereas ADCHASTE did not increase (74 and 74 mm(2)/s, respectively). Two regional recurrences were diagnosed. During treatment, ADCEPI tended to be higher for patients with regional control [(117.3±12.1)×10(-5) mm(2)/s] than for patients with a recurrence [(98.0±4.2)×10(-5) mm(2)/s]. This difference was not seen with ADCHASTE. No correlations between ΔADCEPI and ΔSUV (Standardized Uptake Value) were found in the primary tumor or nodal metastases. CONCLUSIONS: HASTE-DWI seems to be inadequate in early CRT response prediction, compared to EPI-DWI which has potential to predict locoregional outcome. EPI-DWI and 18F-FDG-PET-CT potentially provide independent information in the early response to treatment, since no correlations were found between ΔADCEPI and ΔSUV.

The use of PET-MRI in the follow-up after radiofrequency- and microwave ablation of colorectal liver metastases.

BACKGROUND: Thermal ablation of colorectal liver metastases (CRLM) may result in local progression, which generally appear within a year of treatment. As the timely diagnosis of this progression allows potentially curative local treatment, an optimal follow-up imaging strategy is essential. PET-MRI is a one potential imaging modality, combining the advantages of PET and MRI. The aim of this study is evaluate fluorine-18 deoxyglucose positron emission tomography (FDG) PET-MRI as a modality for detection of local tumor progression during the first year following thermal ablation, as compared to the current standard, FDG PET-CT. The ability of FDG PET-MRI to detect new intrahepatic lesions, and the extent to which FDG PET-MRI alters clinical management, inter-observer variability and patient preference will also be included as secondary outcomes. METHODS/DESIGN: Twenty patients undergoing treatment with radiofrequency or microwave ablation for (recurrent) CRLM will be included in this prospective trial. During the first year of follow-up, patients will be scanned at the VU University Medical Center at 3-monthly intervals using a 4-phase liver CT, FDG PET-CT and FDG PET-MRI. Patients treated with chemotherapy <6 weeks prior to scanning or with a contra-indication for MRI will be excluded. MRI will be performed using both whole body imaging (mDixon) and dedicated liver sequences, including diffusion-weighted imaging, T1 in-phase and opposed-phase, T2 and dynamic contrast-enhanced imaging. The results of all modalities will be scored by 4 individual reviewers and inter-observer agreement will be determined. The reference standard will be histology or clinical follow-up. A questionnaire regarding patients' experience with both modalities will also be completed at the end of the follow-up year. DISCUSSION: Improved treatment options for local site recurrences following CRLM ablation mean that accurate post-ablation staging is becoming increasingly important. The combination of the sensitivity of MRI as a detection method for small intrahepatic lesions with the ability of FDG PET to visualize enhanced metabolism at the ablation site suggests that FDG PET-MRI could potentially improve the accuracy of (early) detection of progressive disease, and thus allow swifter and more effective decision-making regarding appropriate treatment. TRIAL REGISTRATION NUMBER: NCT01895673.

Can we increase the yield of FDG-PET in the preoperative work-up for epilepsy surgery?

PURPOSE: [(18)F] Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) is a semi-invasive, interictal method of localization of hypometabolic epileptic foci. FDG-PET can be useful in the clinical work-up prior to epilepsy surgery, especially in equivocal cases. We investigated whether we could increase the yield of presurgical FDG-PET in patients with difficult epilepsy requiring chronic subdural electrocorticography (ECoG). METHODS: We retrospectively studied patients with refractory focal epilepsy in whom there was uncertainty about the focus localization and who underwent FDG-PET and ECoG. Two experts (epileptologist and nuclear medicine radiologist) together systematically re-assessed the scans visually (PETRE), blinded to their initial reports. Scans were also re-analyzed by comparing them to a normal control dataset with Statistical Parametric Mapping (SPM), using a liberal (PETSPM1), and strict (PETSPM2) statistical threshold. Regions with hypometabolism and regions containing the seizure onset zone (SOZ) in ECoG were marked as positive anatomical regions (PARs). We compared the concordance of these PARs for the different PET re-assessments. We calculated the sensitivity, specificity and accuracy of the PET results for the SOZ. The added value of the re-assessments was evaluated with emphasis on scans initially reported as negative. RESULTS: 41 Patients (63% extra-temporal) were included. PETRE identified the SOZ best, with a sensitivity of 62% and specificity of 93%. PETSPM1 had a sensitivity of 62% and specificity 69%, for PETSPM2 this was 35% and 85% respectively. The overlap between PETRE vs. PETSPM1 and vs. PETSPM2 was 71% and 37%. Visual re-assessment and PETSPM1 identified the SOZ in four out of five scans that were initially reported as negative. CONCLUSIONS: Pre-surgical re-assessment of PET scans is worthwhile in epilepsy patients who undergo ECoG, especially when results were reported as negative before. Visual re-assessment itself has a higher combined specificity, sensitivity and accuracy than SPM analysis alone. SPM analysis could be used as a guide for visual (re-)assessment, because of its high sensitivity.

Transcatheter CT arterial portography and CT hepatic arteriography for liver tumor visualization during percutaneous ablation.

PURPOSE: To evaluate the feasibility of combining transcatheter computed tomography (CT) arterial portography or transcatheter CT hepatic arteriography with percutaneous liver ablation for optimized and repeated tumor exposure. MATERIALS AND METHODS: Study participants were 20 patients (13 men and 7 women; mean age, 59.4 y; range, 40-76 y) with unresectable liver-only malignancies--14 with colorectal liver metastases (29 lesions), 5 with hepatocellular carcinoma (7 lesions), and 1 with intrahepatic cholangiocarcinoma (2 lesions)--that were obscure on nonenhanced CT. A catheter was placed within the superior mesenteric artery (CT arterial portography) or in the hepatic artery (CT hepatic arteriography). CT arterial portography or CT hepatic arteriography was repeatedly performed after injecting 30-60 mL 1:2 diluted contrast material to plan, guide, and evaluate ablation. The operator confidence levels and the liver-to-lesion attenuation differences were assessed as well as needle-to-target mismatch distance, technical success, and technique effectiveness after 3 months. RESULTS: Technical success rate was 100%; there were no major complications. Compared with conventional unenhanced CT, operator confidence increased significantly for CT arterial portography or CT hepatic arteriography cases (P < .001). The liver-to-lesion attenuation differences between unenhanced CT, contrast-enhanced CT, and CT arterial portography or CT hepatic arteriography were statistically significant (mean attenuation difference, 5 HU vs 28 HU vs 70 HU; P < .001). Mean needle-to-target mismatch distance was 2.4 mm ± 1.2 (range, 0-12.0 mm). Primary technique effectiveness at 3 months was 87% (33 of 38 lesions). CONCLUSIONS: In patients with technically unresectable liver-only malignancies, single-session CT arterial portography-guided or CT hepatic arteriography-guided percutaneous tumor ablation enables repeated contrast-enhanced imaging and real-time contrast-enhanced CT fluoroscopy and improves lesion conspicuity.

Whole-body-MR imaging including DWIBS in the work-up of patients with head and neck squamous cell carcinoma: a feasibility study.

OBJECTIVES: To assess the feasibility of whole-body magnetic resonance imaging (WB-MRI) including diffusion-weighted whole-body imaging with background-body-signal-suppression (DWIBS) for the evaluation of distant malignancies in head and neck squamous cell carcinoma (HNSCC); and to compare WB-MRI findings with (18)F-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG-PET/CT) and chest-CT. METHODS: Thirty-three patients with high risk for metastatic spread (26 males; range 48-79 years, mean age 63 ± 7.9 years (mean ± standard deviation) years) were prospectively included with a follow-up of six months. WB-MRI protocol included short-TI inversion recovery and T1-weighted sequences in the coronal plane and half-fourier acquisition single-shot turbo spin-echo T2 and contrast-enhanced-T1-weighted sequences in the axial plane. Axial DWIBS was reformatted in the coronal plane. Interobserver variability was assessed using weighted kappa and the proportion specific agreement (PA). RESULTS: Two second primary tumors and one metastasis were detected on WB-MRI. WB-MRI yielded seven clinically indeterminate lesions which did not progress at follow-up. The metastasis and one second primary tumor were found when combining (18)F-FDG-PET/CT and chest-CT findings. Interobserver variability for WB-MRI was κ=0.91 with PA ranging from 0.82 to 1.00. For (18)F-FDG-PET/CT κ could not be calculated due to a constant variable in the table and PA ranged from 0.40 to 0.99. CONCLUSIONS: Our WB-MRI protocol with DWIBS is feasible in the work-up of HNSCC patients for detection and characterization of distant pathology. WB-MRI can be complementary to (18)F-FDG-PET/CT, especially in the detection of non (18)F-FDG avid second primary tumors.

False-positive uptake of 124I in a laryngeal cyst mimicking thyroid remnant after thyroidectomy and 131i therapy for follicular thyroid carcinoma.

A 46-year-old woman underwent total thyroidectomy followed by I therapy for follicular thyroid carcinoma stage T3 N0 M0. Eleven years after diagnosis, the patient complained about voice changes and feared recurrent disease. Follow-up I PET/CT scan revealed focal uptake in the neck, in the absence of any anatomic substrate on CT. Physical examination including laryngoscopy did not show any tumor or signs of recurrent disease. MRI of the neck demonstrated an oval-shaped lesion in the right false vocal cord. The lesion was removed in toto using carbon dioxide laser. Histological examination demonstrated a benign cyst, and the patient recovered entirely.

18 F-FDG PET standard uptake values of the normal pons in children: establishing a reference value for diffuse intrinsic pontine glioma.

BACKGROUND: Positron emission tomography (PET) scanning with [18 F]fluorodeoxyglucose (18 F-FDG) is a useful diagnostic and prediction tool in brain tumors, but its value in childhood diffuse intrinsic pontine glioma (DIPG) is still unclear. For interpretation of 18 F-FDG PET results in DIPG, uptake values of the normal pons of children of increasing ages are mandatory. The aim of this study was to determine 18 F-FDG standard uptake value ratios (SUVr) of the normal pons and to compare these to those of DIPG. METHODS: We studied 36 subjects with a normal, non-affected pons (aged 5 to 23 years) and 6 patients with DIPG (aged 4 to 17 years) who underwent 18 F-FDG PET scanning. Magnetic resonance imaging (MRI) was co-registered to define the regions of interest. SUVr and SUVrmax for the pons/cerebellum (SUVrp/c) and the pons/occipital lobe (SUVrp/o) were calculated. Independent-samples t tests and Mann-Whitney U tests were used to compare the mean SUVr and Pearson's test for correlations. RESULTS: For the normal pons, mean SUVrp/c and SUVrp/o were 0.65 (±0.054) and 0.51 (±0.056), respectively. No significant correlations were found between the SUVr of the normal pons and sex, age, nor pontine volume. A modest but statistically significant correlation was found between SUVr and post-injection time acquisition timing. For DIPG, mean SUVrp/c and SUVrp/o were 0.74 (±0.20) and 0.65 (±0.30), respectively, while mean SUVrp(max)/c and SUVrp(max)/o were 1.95 (±0.48) and 1.81 (±0.20), respectively. CONCLUSION: The SUVr of the unaffected pons are strikingly constant between children, irrespective of sex and age, and can therefore be well used as a reference value for 18 F-FDG PET studies in DIPG.

Benefit of a second opinion: From metastatic disease to resectable lung cancer with sarcoid-like reaction.

BACKGROUND: Mediastinal lymphadenopathy in combination with lung cancer is suggestive for lymph node metastases but can also have other origins. CASE REPORT: We describe a patient diagnosed with stage IV lung cancer presenting with parenchymal lesions and enlarged mediastinal lymph nodes. A second opinion including FDG-PET scan review and a mediastinoscopy followed by surgery revealed tumor specimens originating from a single primary tumor with a sarcoid-like reaction in the mediastinal lymph nodes, changing the diagnosis from metastasized to resectable lung cancer. DISCUSSION: PET positive lesions are not always synonymous with metastatic disease in the presence of a malignant tumor. Conscientious review of FDG-PET scans and tissue sampling are therefore mandatory to determine definitive staging and subsequent interventions.