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.

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.

Blood-brain barrier P-glycoprotein function in Alzheimer's disease.

A major pathological hallmark of Alzheimer's disease is accumulation of amyloid-ß in senile plaques in the brain. Evidence is accumulating that decreased clearance of amyloid-ß from the brain may lead to these elevated amyloid-ß levels. One of the clearance pathways of amyloid-ß is transport across the blood-brain barrier via efflux transporters. P-glycoprotein, an efflux pump highly expressed at the endothelial cells of the blood-brain barrier, has been shown to transport amyloid-ß. P-glycoprotein function can be assessed in vivo using (R)-[(11)C]verapamil and positron emission tomography. The aim of this study was to assess blood-brain barrier P-glycoprotein function in patients with Alzheimer's disease compared with age-matched healthy controls using (R)-[(11)C]verapamil and positron emission tomography. In 13 patients with Alzheimer's disease (age 65 ± 7 years, Mini-Mental State Examination 23 ± 3), global (R)-[(11)C]verapamil binding potential values were increased significantly (P = 0.001) compared with 14 healthy controls (aged 62 ± 4 years, Mini-Mental State Examination 30 ± 1). Global (R)-[(11)C]verapamil binding potential values were 2.18 ± 0.25 for patients with Alzheimer's disease and 1.77 ± 0.41 for healthy controls. In patients with Alzheimer's disease, higher (R)-[(11)C]verapamil binding potential values were found for frontal, parietal, temporal and occipital cortices, and posterior and anterior cingulate. No significant differences between groups were found for medial temporal lobe and cerebellum. These data show altered kinetics of (R)-[(11)C]verapamil in Alzheimer's disease, similar to alterations seen in studies where P-glycoprotein is blocked by a pharmacological agent. As such, these data indicate that P-glycoprotein function is decreased in patients with Alzheimer's disease. This is the first direct evidence that the P-glycoprotein transporter at the blood-brain barrier is compromised in sporadic Alzheimer's disease and suggests that decreased P-glycoprotein function may be involved in the pathogenesis of Alzheimer's disease.

Incidence and treatment of local site recurrences following RFA of colorectal liver metastases.

BACKGROUND: Patients with colorectal liver metastases (CRLM) who are ineligible for curative surgery are potential candidates for radiofrequency ablation (RFA). Although RFA has emerged as a well accepted and documented treatment modality, there are still some reservations because of initially high rates of local site recurrences (LSR). The aim of the present study was to evaluate LSR levels following RFA treatment, with a specific focus on re-treatment and survival. PATIENTS AND METHODS: All patients ineligible for curative resection of CRLM and undergoing RFA alone or in combination with resection were prospectively included from July 2000 to December 2010 and retrospectively analyzed. Patients with untreatable extrahepatic disease were excluded. FDG PET-CT was conducted at 3-6 month intervals after RFA. Patients with LSR were evaluated for re-treatment. RESULTS: A total of 132 patients were treated with RFA, which was combined with resection in 64 patients. A total of 290 lesions were ablated, with a mean number of 2.19 per patient and a mean size of 2.2 cm. Median survival was 41 months, with a 3- and 5-year survival of, respectively, 60 and 30.8 %. Following initial RFA, 39 patients developed an LSR in 40 ablated lesions, and local recurrence was strongly related to lesion size. Re-treatment could be performed in 26/39 patients, of whom eight remained disease-free. CONCLUSIONS: Radiofrequency ablation can be applied to CRLM of less than 3 cm with curative intent. In the absence of extensive intrahepatic or extrahepatic disease, renewed treatment of local recurrences should be considered and is often successful.

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.

Reduced parahippocampal and lateral temporal GABAA-[11C]flumazenil binding in major depression: preliminary results.

PURPOSE: Major depressive disorder (MDD) has been related to both a dysfunctional gamma-amino butyric acid (GABA) system and to hyperactivity of the hypothalamic-pituitary-adrenal axis (HPA). Although GABA has been suggested to inhibit HPA axis activity, their relationship has never been studied at the level of the central GABA(A)-benzodiazepine receptor in depressed patients or in relation to antidepressant treatment. METHODS: Eleven depressed outpatients were compared, before and after treatment with citalopram, with nine age-matched healthy controls. The subjects were scanned using the positron emission tomography (PET) tracer [(11)C]flumazenil ([(11)C]FMZ). Parametric voxel-by-voxel Logan plots were compared with methods based on regions of interest (ROI), to provide volume of distribution (V(T)) and binding potential (BP(ND)) values. Plasma GABA levels were determined and a dexamethasone-corticotropin releasing hormone (DEX-CRH) test was performed. RESULTS: In MDD, parametric voxel-by-voxel Logan plots showed bilateral reduced [(11)C]FMZ binding in the parahippocampal gyrus and right lateral superior temporal gyrus (p uncorrected < or =0.001). In the temporal area, [(11)C]FMZ binding showed a strong inverse correlation with HPA axis activity. Plasma GABA did not discriminate MDD from controls, but correlated inversely with [(11)C]FMZ binding in the right insula. Following treatment with citalopram, voxel-based analysis revealed reduced binding in the right lateral temporal gyrus and dorsolateral prefrontal cortex. CONCLUSION: The bilateral reduction in limbic parahippocampal and right temporal [(11)C]FMZ binding found in MDD indicates decreased GABA(A)-benzodiazepine receptor complex affinity and/or number. The inverse relationship between GABA(A) binding in the temporal lobe and HPA axis activity, suggests that HPA axis hyperactivity is partly due to reduced GABA-ergic inhibition.

FDG PET and PET/CT: EANM procedure guidelines for tumour PET imaging: version 1.0.

The aim of this guideline is to provide a minimum standard for the acquisition and interpretation of PET and PET/CT scans with [18F]-fluorodeoxyglucose (FDG). This guideline will therefore address general information about[18F]-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET/CT) and is provided to help the physician and physicist to assist to carrying out,interpret, and document quantitative FDG PET/CT examinations,but will concentrate on the optimisation of diagnostic quality and quantitative information.

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.

Improved selection of patients for hepatic surgery of colorectal liver metastases with (18)F-FDG PET: a randomized study.

UNLABELLED: With the increasing possibilities for surgical treatment of colorectal liver metastases, careful selection of patients who may benefit from surgical treatment becomes critical. The addition of PET to (18)F-FDG may significantly improve conventional staging by CT. Up to now, definitive evidence that the addition of (18)F-FDG PET to conventional staging leads to superior clinical results and improved clinical management in these patients has been lacking. In this randomized controlled trial in patients with colorectal liver metastases, we investigated whether the addition of (18)F-FDG PET is beneficial and reduces the number of futile laparotomies. METHODS: A total of 150 patients with colorectal liver metastases selected for surgical treatment by imaging with CT were randomly assigned to CT only (n = 75) or CT plus (18)F-FDG PET (n = 75). Patients were followed up for at least 3 y. The primary outcome measure was futile laparotomy, defined as any laparotomy that did not result in complete tumor treatment, that revealed benign disease, or that did not result in a disease-free survival period longer than 6 mo. RESULTS: Patient and tumor characteristics were similar for both groups. The number of futile laparotomies was 34 (45%) in the control arm without (18)F-FDG PET and 21 (28%) in the experimental arm with (18)F-FDG PET; the relative risk reduction was 38% (95% confidence interval, 4%-60%, P = 0.042). CONCLUSION: The number of futile laparotomies was reduced from 45% to 28%; thus, the addition of (18)F-FDG PET to the work-up for surgical resection of colorectal liver metastases prevents unnecessary surgery in 1 of 6 patients.

Improved detection of recurrent laryngeal tumor after radiotherapy using (18)FDG-PET as initial method.

BACKGROUND AND PURPOSE: Timely detection of recurrent laryngeal tumor after radiation is an important predictive factor for curation as well as preservation of laryngeal function. Direct laryngoscopy under general anesthesia with taking of biopsies is the standard diagnostic procedure to detect recurrence when suspicion is raised. This, however, is an invasive and potentially damaging technique. Hence, a non-invasive diagnostic procedure, such as (18)FDG-PET to stratify patients for direct laryngoscopy could be useful. (18)FDG-PET is interpreted visually so that observer variation may affect clinical practice. In the present study, we therefore investigated this aspect of reproducibility. PATIENTS AND METHODS: Thirty consecutive patients suspected of recurrent laryngeal carcinoma after radiotherapy underwent (18)FDG-PET and direct laryngoscopy under general anesthesia with taking of biopsies. (18)FDG-PET scans were reported by nine nuclear medicine physicians and residents, using a three-point scaling system. The reference was the absence or appearance of a local recurrence in the 12 months following (18)FDG-PET. RESULTS: Eight patients had biopsy proven recurrent laryngeal carcinoma. Sensitivity of (18)FDG-PET was 88% (95% CI 53-98%) and specificity was 82% (95% CI 62-93%). The observers had a moderate to reasonable agreement (weighted kappa 0.45 (95% CI 0.20-0.69)) vs. the clinical gold standard and interobserver kappa was 0.54 (95% CI 0.40-0.69). CONCLUSION: (18)FDG-PET seems to be a promising technique to detect recurrent laryngeal carcinoma after radiotherapy, and selecting patients for direct laryngoscopy. This will avoid futile invasive procedures. Interobserver agreement and variability is reasonable using this technique, but training is necessary. Studies comparing different strategies to select patients for direct laryngoscopy in case of suspected recurrence are warranted.

Bone metabolism after total hip revision surgery with impacted grafting: evaluation using H2 15O and [18F]fluoride PET; a pilot study.

PURPOSE: To evaluate bone blood flow and bone formation in patients after total hip revision surgery with impacted bone grafting using H2 15O and [18F]fluoride positron emission tomography (PET). PROCEDURES: To asses bone blood flow and bone metabolism in bone allograft after impaction grafting, four patients treated with total hip revision surgery were enrolled prospectively in this study. Six patients scheduled for primary hip arthroplasties were included as a control group. The study protocol consisted of three H2 15O and [18F]fluoride PET scans in each patient. RESULTS: Bone blood flow increased significantly compared to the preoperative state in patients treated for primary hip arthroplasty. In patients undergoing revision surgery, bone blood flow was twofold to threefold higher compared to the preoperative state, but did not reach significance. Bone metabolism in patients undergoing revision was threefold higher 2 weeks postoperatively compared to the primary hip group. We found a significant correlation between Ki and bone blood flow. CONCLUSIONS: Allogeneic bone grafts induce a higher rate of local periprosthetic bone formation compared to periprosthetic bone formation after a primary total hip placement. In vivo coupling between bone blood flow and bone metabolism suggests that bone metabolism in allogeneic bone grafts may partly rely on bone blood flow adaptations.

The Netherlands protocol for standardisation and quantification of FDG whole body PET studies in multi-centre trials.

INTRODUCTION: Several studies have shown the usefulness of positron emission tomography (PET) quantification using standardised uptake values (SUV) for diagnosis and staging, prognosis and response monitoring. Many factors affect SUV, such as patient preparation procedures, scan acquisition, image reconstruction and data analysis settings, and the variability in methodology across centres prohibits exchange of SUV data. Therefore, standardisation of 2-[(18)F] fluoro-2-deoxy-D-glucose (FDG) PET whole body procedures is required in multi-centre trials. METHODS: A protocol for standardisation of quantitative FDG whole body PET studies in the Netherlands (NL) was defined. This protocol is based on standardisation of: (1) patient preparation; (2) matching of scan statistics by prescribing dosage as function of patient weight, scan time per bed position, percentage of bed overlap and image acquisition mode (2D or 3D); (3) matching of image resolution by prescribing reconstruction settings for each type of scanner; (4) matching of data analysis procedure by defining volume of interest methods and SUV calculations and; (5) finally, a multi-centre QC procedure is defined using a 20-cm diameter phantom for verification of scanner calibration and the NEMA NU 2 2001 Image Quality phantom for verification of activity concentration recoveries (i.e., verification of image resolution and reconstruction convergence). DISCUSSION: This paper describes a protocol for standardization of quantitative FDG whole body multi-centre PET studies. CONCLUSION: The protocol was successfully implemented in the Netherlands and has been approved by the Netherlands Society of Nuclear Medicine.

Retrospective attenuation correction of PET data for radiotherapy planning using a free breathing CT.

PURPOSE: To evaluate the image quality of retrospectively attenuation corrected Positron Emission Tomography (PET) scans used for gross tumor volume (GTV) delineation in lung cancer patients. MATERIALS AND METHODS: Data of 13 lymph node positive lung cancer patients were acquired on separate CT and PET scanners under free breathing conditions (for radiotherapy planning). First we determined a protocol for CT/PET registration. Second, we compared the image quality of attenuation-corrected PET images using positron transmission images and CT images, in terms of signal-to-noise ratio (SNR) and lesion-to-background ratio (contrast). RESULTS: The largest differences between manual and automatic CT/PET registration were found in the anterior-posterior direction with a mean of 1.8 mm (SD 1.0 mm). Differences in rotations were always smaller than 1.0 degrees . The attenuation-corrected images using CT showed a larger SNR (mean 30%, SD 17%) and larger contrast (mean 14.0%, SD 8.5%) compared to attenuation-corrected images using positron transmission. For lymph nodes, the mean contrast was 16% (SD 6.4%) larger. CONCLUSIONS: This study demonstrated that attenuation correction based on CT provides a better image quality for GTV delineation than when using positron transmission for attenuation correction. Retrospective attenuation correction of PET scans based on registered CT is a good alternative for a dedicated PET/CT scanner if a free-breathing CT is available, e.g., for radiotherapy planning, and allows the use of CT with diagnostic quality for attenuation correction.

Performance of immuno-positron emission tomography with zirconium-89-labeled chimeric monoclonal antibody U36 in the detection of lymph node metastases in head and neck cancer patients.

PURPOSE: Immuno-positron emission tomography (PET), the combination of PET with monoclonal antibodies (mAb), is an attractive option to improve tumor detection and to guide mAb-based therapy. The long-lived positron emitter zirconium-89 ((89)Zr) has ideal physical characteristics for immuno-PET with intact mAbs but has never been used in a clinical setting. In the present feasibility study, we aimed to evaluate the diagnostic imaging performance of immuno-PET with (89)Zr-labeled-chimeric mAb (cmAb) U36 in patients with squamous cell carcinoma of the head and neck (HNSCC), who were at high risk of having neck lymph node metastases. EXPERIMENTAL DESIGN: Twenty HNSCC patients, scheduled to undergo neck dissection with or without resection of the primary tumor, received 75 MBq (89)Zr coupled to the anti-CD44v6 cmAb U36 (10 mg). All patients were examined by computed tomography (CT) and/or magnetic resonance imaging (MRI) and immuno-PET before surgery. Six patients also underwent PET with (18)F-fluoro-2-deoxy-d-glucose. Immuno-PET scans were acquired up to 144 hours after injection. Diagnostic findings were recorded per neck side (left or right) as well as per lymph node level (six levels per side), and compared with histopathologic outcome. For this purpose, the CT/MRI scores were combined and the best of both scores was used for analysis. RESULTS: Immuno-PET detected all primary tumors (n = 17) as well as lymph node metastases in 18 of 25 positive levels (sensitivity 72%) and in 11 of 15 positive sides (sensitivity 73%). Interpretation of immuno-PET was correct in 112 of 121 operated levels (accuracy 93%) and in 19 of 25 operated sides (accuracy 76%). For CT/MRI, sensitivities of 60% and 73% and accuracies of 90% and 80% were found per level and side, respectively. In the six patients with seven tumor-involved neck levels and sides, immuno-PET and (18)F-fluoro-2-deoxy-d-glucose PET gave comparable diagnostic results. CONCLUSION: In this study, immuno-PET with (89)Zr-cmAb U36 performed at least as good as CT/MRI for detection of HNSCC lymph node metastases.

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.

Reduction of observer variation using matched CT-PET for lung cancer delineation: a three-dimensional analysis.

PURPOSE: Target delineation using only CT information introduces large geometric uncertainties in radiotherapy for lung cancer. Therefore, a reduction of the delineation variability is needed. The impact of including a matched CT scan with 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) and adaptation of the delineation protocol and software on target delineation in lung cancer was evaluated in an extensive multi-institutional setting and compared with the delineations using CT only. METHODS AND MATERIALS: The study was separated into two phases. For the first phase, 11 radiation oncologists (observers) delineated the gross tumor volume (GTV), including the pathologic lymph nodes of 22 lung cancer patients (Stages I-IIIB) on CT only. For the second phase (1 year later), the same radiation oncologists delineated the GTV of the same 22 patients on a matched CT-FDG-PET scan using an adapted delineation protocol and software (according to the results of the first phase). All delineated volumes were analyzed in detail. The observer variation was computed in three dimensions by measuring the distance between the median GTV surface and each individual GTV. The variation in distance of all radiation oncologists was expressed as a standard deviation. The observer variation was evaluated for anatomic regions (lung, mediastinum, chest wall, atelectasis, and lymph nodes) and interpretation regions (agreement and disagreement; i.e., >80% vs. <80% of the radiation oncologists delineated the same structure, respectively). All radiation oncologist-computer interactions were recorded and analyzed with a tool called "Big Brother." RESULTS: The overall three-dimensional observer variation was reduced from 1.0 cm (SD) for the first phase (CT only) to 0.4 cm (SD) for the second phase (matched CT-FDG-PET). The largest reduction in the observer variation was seen in the atelectasis region (SD 1.9 cm reduced to 0.5 cm). The mean ratio between the common and encompassing volume was 0.17 and 0.29 for the first and second phases, respectively. For the first phase, the common volume was 0 in 4 patients (i.e., no common point for all GTVs). In the second phase, the common volume was always >0. For all anatomic regions, the interpretation differences among the radiation oncologists were reduced. The amount of disagreement was 45% and 18% for the first and second phase, respectively. Furthermore, the mean delineation time (12 vs. 16 min, p<0.001) and mean number of corrections (25 vs. 39, p<0.001) were reduced in the second phase compared with the first phase. CONCLUSION: For high-precision radiotherapy, the delineation of lung target volumes using only CT introduces too great a variability among radiation oncologists. Implementing matched CT-FDG-PET and adapted delineation protocol and software reduced observer variation in lung cancer delineation significantly with respect to CT only. However, the remaining observer variation was still large compared with other geometric uncertainties (setup variation and organ motion).

18F-FDG PET versus CT for the detection of enteropathy-associated T-cell lymphoma in refractory celiac disease.

UNLABELLED: Refractory celiac disease (RCD) can evolve into enteropathy-associated T-cell lymphoma (EATL). 18F-FDG PET has been reported to discriminate between RCD and EATL. Because prospective data are lacking, we designed a prospective study to evaluate the potential of 18F-FDG PET for detection of EATL in patients with RCD and compared the results with those obtained using abdominal CT in a referral center. METHODS: Between April 2003 and April 2005, 8 consecutive patients (median age, 66 y; range, 52-89 y) with EATL and 30 patients (median age, 61 y; range, 44-71 y) with RCD were included. CT and 18F-FDG PET were performed on all patients. Histologic evidence of EATL was identified in tissue samples obtained during upper gastrointestinal endoscopy or surgical resection. RESULTS: Villous atrophy was found in all patients with RCD and all (except 1) patients with EATL in nontumoral mucosa. Histologic examination of 1 patient with EATL localized in the duodenum showed intraepithelial lymphocytosis only. 18F-FDG PET could reveal sites histologically proven to be EATL in all 8 patients, whereas CT showed normal findings in 1 patient with EATL. 18F-FDG PET detected unsuspected extraintestinal sites affected by EATL in 2 patients. CT showed abnormalities such as a thickened small-bowel wall or lymphadenopathy in 14 patients with RCD lacking evidence of EATL at follow-up. 18F-FDG PET findings were positive in 3 and equivocal in another 3 patients with RCD. 18F-FDG PET was more sensitive and specific than CT (100% vs. 87% and 90% vs. 53%, respectively). CONCLUSION: Our data show that 18F-FDG PET is more sensitive in detecting EATL in patients with RCD than is CT. 18F-FDG PET, in addition to conventional CT, is recommended for evaluating patients with RCD.

Microvessel density and p53 in detecting cervical cancer by FDG PET in cases of suspected recurrence.

PURPOSE: Cervical cancer is the second most frequently diagnosed cancer in women worldwide. About one-third of patients experience recurrent disease. A better chance of survival might be achieved by the early detection of recurrent cervical cancer. [(18)F]fluoro-2-deoxy-D-glucose (FDG) PET could be a promising imaging modality for this purpose, given that FDG PET has high diagnostic efficacy. Ideally, pre-selection of patients should be performed before considering FDG PET. The purpose of this study was to investigate parameters of primary cervical cancer associated with recurrence as a basis for pre-selection of patients in whom FDG PET should be performed. METHODS: Thirty-eight cervical cancer patients, clinically suspected of having recurrent disease, underwent FDG PET. Tissue from primary tumours and nine histologically confirmed metastases was analysed for biomarkers possibly related to glucose metabolism and prognosis (vascular endothelial growth factor, CD31 for microvessel density, glucose transporter-1, hexokinases I, II and III, Ki67, p53, hypoxia-inducible factor 1alpha, and degree of infiltration by lymphocytes and macrophages). RESULTS: Based on clinical outcome, sensitivity and specificity of FDG PET were 96% and 100%, respectively. Cox regression revealed microvessel density and p53 (tumour suppressor protein) to be the two most important biomarkers for prediction of recurrence (hazard ratios 2.54 and 2.28, respectively). By combining these two biomarkers in a parallel test, sensitivity and specificity in predicting recurrence were 87% and 71%, respectively. Leave-one-out cross-validation demonstrated predictive validity of a model based on microvessel density and p53. CONCLUSION: In this first study of its kind, we have demonstrated that microvessel density and p53 profiles could be important in pre-selecting cervical cancer patients for detection of recurrence by FDG PET.