Prenatal MR imaging of congenital diaphragmatic hernias: association of MR fetal lung volume with the need for postnatal prosthetic patch repair.

OBJECTIVE: To assess whether the need for postnatal prosthetic patch repair of the diaphragmatic defect in neonates with a congenital diaphragmatic hernia (CDH) is associated with the antenatal measured observed-to-expected magnetic resonance fetal lung volume (o/e MR-FLV). METHODS: The o/e MR-FLV was calculated in 247 fetuses with isolated CDH. Logistic regression analysis was used to assess the prognostic value of the individual o/e MR-FLV for association with the need for postnatal patch repair. RESULTS: Seventy-seven percent (77%) of patients with a CDH (190/247) required prosthetic patch repair and the defect was closed primarily in 23% (57/247). Patients requiring a patch had a significantly lower o/e MR-FLV (27.7 ± 10.2%) than patients with primary repair (40.8 ± 13.8%, p < 0.001, AUC = 0.786). With an o/e MR-FLV of 20%, 92% of the patients required patch repair, compared to only 24% with an o/e MR-FLV of 60%. The need for a prosthetic patch was further influenced by the fetal liver position (herniation/no herniation) as determined by magnetic resonance imaging (MRI; p < 0.001). Fetal liver position, in addition to the o/e MR-FLV, improves prognostic accuracy (AUC = 0.827). CONCLUSION: Logistic regression analysis based on the o/e MR-FLV is useful for prenatal estimation of the prosthetic patch requirement in patients with a CDH. In addition to the o/e MR-FLV, the position of the liver as determined by fetal MRI helps improve prognostic accuracy. KEY POINTS: • The o/e MR-FLV is associated with the need for postnatal patch repair in CDH. • The need for a patch is associated with a significantly lower o/e MR-FLV (p < 0.001). • The patch requirement is also influenced by fetal liver position. • Fetal liver position, in addition to the o/e MR-FLV, improves prognostic accuracy. • CDH-fetuses with a high probability for patch requirement can be identified prenatally.

Repetitive MR measurements of lung volume in fetuses with congenital diaphragmatic hernia: individual development of pulmonary hypoplasia during pregnancy and calculation of weekly lung growth rates.

OBJECTIVE: To investigate individual changes in fetal lung volume (FLV) in fetuses with isolated congenital diaphragmatic hernia (CDH) and to calculate weekly growth rates of the FLV using serial MR examinations during pregnancy. METHODS: MR-FLV was measured in 89 fetuses with CDH. All fetuses received two MRIs. A mean weekly growth rate of the FLV was determined for each fetus and compared with the growth rate of healthy fetuses. RESULTS: Mean observed-to-expected MR-FLV (o/e MR-FLV) measured at the first MRI was 33.3 ± 12.2% and 29.5 ± 10.9% at the second MRI. In 61% of all fetuses (54/89) the o/e MR-FLV decreased during pregnancy, 26% (23/89) showed an increase in the o/e MR-FLV and 13 % (12/89) had stable values. First and last o/e MR-FLV values were significantly associated with mortality and neonatal extracorporeal membrane oxygenation (ECMO) requirement with a higher prognostic accuracy of MR-FLV measurements near delivery. Patients with CDH had lower weekly lung growth rates than healthy fetuses. There was a significant difference in the mean weekly growth rate between survivors and non-survivors and patients with and without ECMO requirement. CONCLUSION: Individual development of FLV in patients with CDH during pregnancy is extremely variable. Follow-up MR-FLV measurements are advisable before deciding upon pre- and postnatal therapeutic options. KEY POINTS: • Lung development in congenital diaphragmatic hernia (CDH) during pregnancy is extremely variable. • MRI demonstrates that lung growth rate is reduced in fetuses with CDH. • The final observed-to-expected fetal lung volume provides the best prognostic information. • Follow-up measurements are advisable before deciding upon therapeutic options.

MRI-based ratio of fetal lung volume to fetal body volume as a new prognostic marker in congenital diaphragmatic hernia.

OBJECTIVE: The objective of our study was to evaluate the prognostic accuracy of the MRI-based ratio of fetal lung volume (FLV) to fetal body volume (FBV) for predicting survival and the need for extracorporeal membrane oxygenation (ECMO) therapy in fetuses with congenital diaphragmatic hernia (CDH). MATERIALS AND METHODS: MRI was performed in 96 fetuses (34 females and 62 males; mean gestational age, 33 ± 5 [SD] weeks; range, 23-39 weeks) with CDH and 44 healthy control subjects. FLV and FBV were measured for each fetus by one of three investigators, and we calculated the FLV/FBV ratio. Additionally, a subgroup analysis of growth-restricted fetuses was performed. Logistic regression analysis was used to model the dependence of survival and ECMO requirement on the FLV/FBV ratio. Prognostic accuracy was evaluated by applying the area under the curve (AUC). RESULTS: Seventy-eight of the 96 (81%) fetuses survived and 35 (36%) neonates needed ECMO therapy. The FLV/FBV ratio was significantly higher in fetuses who survived (p < 0.0001; AUC = 0.829). Neonates who received ECMO therapy showed a significantly lower prenatal FLV/FBV ratio (p = 0.0001; AUC = 0.811) than neonates who did not need ECMO therapy. A subgroup analysis (n = 13) showed a trend toward a higher FLV/FBV ratio of survivors in comparison with nonsurvivors (p = 0.065; AUC = 0.875). CONCLUSION: In our study, the MRI-based FLV/FBV ratio was able to predict neonatal survival and ECMO requirement in children with CDH with high accuracy. Unlike other prognostic parameters, FLV/FBV ratio is independent of a reference to a control group and may enhance prognostic accuracy particularly in growth-restricted neonatal patients.

Fetal lung volume in congenital diaphragmatic hernia: association of prenatal MR imaging findings with postnatal chronic lung disease.

PURPOSE: To assess whether chronic lung disease (CLD) in surviving infants with congenital diaphragmatic hernia (CDH) is associated with lung hypoplasia on the basis of the results of antenatal observed-to-expected fetal lung volume (FLV) ratio measurement at magnetic resonance (MR) imaging. MATERIALS AND METHODS: The study received approval from the institutional review board, with waiver of informed consent for this retrospective review from patients who had previously given informed consent for prospective studies. The ratio of observed to expected FLV at MR imaging was calculated in 172 fetuses with CDH. At postpartum day 28, the need for supplemental oxygen implicated the diagnosis of CLD. At day 56, patients with CLD were assigned to one of three groups-those with mild, moderate, or severe CLD-according to their demand for oxygen. Logistic regression analysis was used to assess the prognostic value of the individual observed-to-expected FLV ratio for association with postnatal development of CLD. RESULTS: Children with CLD were found to have significantly smaller observed-to-expected FLV ratios at MR imaging than infants without CLD (P < .001). Grading of CLD revealed significant differences in observed-to-expected FLV ratio between patients with mild CLD and those with moderate (P = .012) or severe (P = .007) CLD. For an observed-to-expected FLV ratio of 5%, 99% of patients with CDH developed CLD, compared with less than 5% of fetuses with an observed-to-expected FLV ratio of 50%. Perinatally, development and grade of CLD were further influenced by the need for extracorporeal membrane oxygenation (ECMO) (P < .001) and gestational age at delivery (P = .009). CONCLUSION: Manifestation of CLD in surviving infants with CDH is associated with the prenatally determined observed-to-expected FLV ratio. Early neonatal therapeutic decisions can additionally be based on this ratio. Perinatally, ECMO requirement and gestational age at delivery are useful in further improving the estimated probability of CLD.

Periodic MRI lung volume assessment in fetuses with congenital diaphragmatic hernia: prediction of survival, need for ECMO, and development of chronic lung disease.

OBJECTIVE: The purpose of the study was to investigate the ability to predict survival, need for extracorporeal membrane oxygenation (ECMO), and incidence of chronic lung disease in patients with congenital diaphragmatic hernia in the context of a classification into three different times of gestation (< 28, 28-32, and > 32 weeks) by assessing the ratio between observed and expected MRI fetal lung volume. MATERIALS AND METHODS: The data analysis included 226 fetuses with congenital diaphragmatic hernia. MRI was performed at different times of gestation with a T2-weighted HASTE sequence. Receiver operating characteristic curve analysis was performed to investigate the prognostic value of assessment of the ratio between observed and expected MRI fetal lung volumes at different stages of fetal growth. RESULTS: For all reviewed times of gestation, the ratio between observed and expected MRI fetal lung volumes had almost equivalent statistically significant differences for neonatal survival (p ≤ 0.0029), need for ECMO therapy (p ≤ 0.0195), and development of chronic lung disease (p ≤ 0.0064). Results with high prognostic accuracy for early and for medium and late times in gestation also were obtained. Receiver operating characteristic analysis showed the highest area under the curve (≥ 0.819) for neonatal survival. CONCLUSION: In patients with congenital diaphragmatic hernia, the relation between observed and expected MRI fetal lung volume is a valuable prognostic parameter for predicting neonatal mortality, morbidity represented by the development of chronic lung disease, and the need for ECMO therapy in early gestation (< 28 weeks) as well as later gestation with no statistically significant differences.

Preoperative Hilar and Mediastinal Lymph Node Staging in Patients with Suspected or Diagnosed Lung Cancer: Accuracy of 18F-FDG-PET/CT:A Retrospective Cohort Study of 138 Patients.

The aim of this study was to evaluate the diagnostic accuracy of integrated 18F-fluorodeoxyglucose positron emission computed tomography (18F-FDG-PET/CT) in hilar and mediastinal lymph node (HMLN) staging of suspected or proven lung cancer, and to investigate potential risk factors for false negative and false positive HMLN metastases. We retrospectively analyzed 162 consecutive patients with suspected or pathologically proven non-small cell lung cancer (NSCLC). The receiver operating characteristic (ROC) curve was generated to determine the diagnostic efficacy of 18F-FDG-PET/CT. Univariate and multivariate analyses were conducted to detect risk factors of false positives and false negatives. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of integrated 18F-FDG-PET/CT in detecting HMLN metastases were 59.1% (26/44), 69.1% (65/94), 47.3% (26/55), 78.3% (65/83), and 65.9% (91/138), respectively. The ROC curve showed an area under the curve (AUC) of 0.625 (95%-CI 0.468-0.782). The incidence of false negative and false positive HMLN metastases was 21.7% (18/83) and 52.7% (29/55), respectively. Our data shows that integrated 18F-FDG-PET/CT staging provides lower specificity and sensitivity. This confirms the ESTS guideline on lymph node staging for PET-positive HMLN. Yet it advocates more invasive staging even for PET-negative HMLN.

Histology of the Primary Tumor Correlates with False Positivity of Integrated 18F-FDG-PET/CT Lymph Node Staging in Resectable Lung Cancer Patients.

This study aimed to evaluate the diagnostic accuracy and false positivity rate of lymph node (LN) staging assessed by integrated 18F-fluorodeoxyglucose positron emission computed tomography (18F-FDG-PET/CT) in patients with operable lung cancer to the tumor histology. In total, 129 consecutive patients with non-small-cell lung cancer (NSCLC) undergoing anatomical lung resections were included. Preoperative LN staging was evaluated in the relationship to the histology of the resected specimens (group 1: lung adenocarcinoma/LUAD; group 2: squamous cell carcinoma/SQCA). Statistical analysis was performed by the Mann-Whitney U-test, the chi2 test, and binary logistic regression analysis. To establish an easy-to-use algorithm for the identification of LN false positivity, a decision tree including clinically meaningful parameters was generated. In total, 77 (59.7%) and 52 (40.3%) patients were included in the LUAD and SQCA groups, respectively. SQCA histology, non-G1 tumors, and tumor SUVmax > 12.65 were identified as independent predictors of LN false positivity in the preoperative staging. The corresponding ORs and their 95% CIs were 3.35 [1.10-10.22], p = 0.0339; 4.60 [1.06-19.94], p = 0.0412; and 2.76 [1.01-7.55], and p = 0.0483. The preoperative identification of false-positive LNs is an important aspect of the treatment regimen for patients with operable lung cancer; thus, these preliminary findings should be further evaluated in larger patient cohorts.

Re-irradiation in recurrent malignant glioma: prognostic value of [18F]FET-PET.

The aim of the present study is to determine new positron emission tomography (PET) imaging-related factors predictive of progression-free survival as well as survival in patients with recurrent malignant glioma (MG) prior to and after re-irradiation. Fifty-six patients with recurrent MG who underwent re-irradiation treatment and pretherapeutic dynamic [(18)F]-fluoroethyl-L-tyrosine (FET)-PET scan were retrospectively analyzed. The prognostic value of different parameters, such as biological tumor volume, maximal tumor uptake (SUV(max)/BG), mean tumor uptake (SUV(mean)/BG), as well as uptake kinetics, was evaluated. [(18)F]FET uptake kinetics was classified according to a five-point rating as category G(1-2) (strongly/mainly increasing kinetics), G(3) (mixed 1:1), or G(4-5) (mainly/strongly decreasing kinetics). Patients within the pretherapeutic kinetic group G(4-5) had significantly worse survival than the other two groups (p = 0.01). Multivariate analysis revealed that histologic grade, Karnofsky Performance Score (KPS), and kinetic group were independent significant predictors for survival after re-irradiation. The uptake kinetics of [(18)F]FET-PET is an independent determinant of overall and to a lesser extent also progression-free survival. Thus, [(18)F]FET-PET kinetics may provide valuable additional prognostic information for treatment decisions.

Right- versus left-sided congenital diaphragmatic hernia: postnatal outcome at a specialized tertiary care center.

OBJECTIVE: To systematically investigate the impact of the location of the defect in congenital diaphragmatic hernia on neonatal mortality and morbidity with a special focus on survival at discharge, extracorporeal membrane oxygenation requirement, and the development of chronic lung disease. DESIGN: Retrospective tertiary care center study with a matched-pair analysis of all fetuses that were treated for congenital diaphragmatic hernia between 2004 and 2009. SETTING: A specialized tertiary care center for fetuses with congenital diaphragmatic hernia. PATIENTS: Complete sets of data were available for 106 patients with congenital diaphragmatic hernia. For 17 of 18 infants with right-sided congenital diaphragmatic hernia we were able to allocate infants with left-sided congenital diaphragmatic hernia with no relevant difference in previously described prognostic factors, such as pulmonary hypoplasia and liver herniation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: There was a strong trend toward better survival in infants with right-sided congenital diaphragmatic hernia than with left-sided congenital diaphragmatic hernia (94% vs. 70%; p = .07). More neonates with left-sided congenital diaphragmatic hernia died of severe pulmonary hypertension despite extracorporeal membrane oxygenation. Fewer neonates with right-sided congenital diaphragmatic hernia died, yet higher degrees of pulmonary hypoplasia and oxygen requirement were observed despite extracorporeal membrane oxygenation. CONCLUSIONS: In congenital diaphragmatic hernia, the location of the defect has a substantial impact on postnatal survival and the development of chronic lung disease. In left-sided congenital diaphragmatic hernia, pulmonary hypertension resistant to therapeutic management, including extracorporeal membrane oxygenation, is more common and is associated with a higher rate of neonatal demise. Right-sided congenital diaphragmatic hernia infants have an increased benefit from extracorporeal membrane oxygenation but the better survival entails a higher rate of chronic lung disease.

Congenital diaphragmatic hernia: predictive value of MRI relative lung-to-head ratio compared with MRI fetal lung volume and sonographic lung-to-head ratio.

OBJECTIVE: The purpose of this study was to evaluate the prognostic accuracy of a new MRI-based relative lung-to-head ratio in regard to neonatal survival and need for extracorporeal membrane oxygenation (ECMO) in the care of fetuses with congenital diaphragmatic hernia (CDH) and to compare it with the previously described sonographic relative lung-to-head ratio and relative fetal lung volume assessed at antenatal MRI. MATERIALS AND METHODS: Sonographic lung-to-head ratio and MRI fetal lung volume were measured in 90 fetuses (mean gestational age, 31.4+/-4.1 weeks) with CDH. Sonographic relative lung-to-head ratio and MRI relative fetal lung volume were assessed by expressing the observed sonographic lung-to-head ratio and MRI fetal lung volume as a percentage of the expected parameter value. The new MRI relative lung-to-head ratio was assessed as a percentage of the expected MRI lung-to-head ratio based on MRI fetal lung volume and MRI head circumference measurements. Measurements for survival and ECMO requirement were determined with the area under the curve (AUC). Data were analyzed for left-sided defects, right-sided defects, and associated liver herniation. RESULTS: Among fetuses with left-sided CDH, all parameters were excellent in determining neonatal survival and need for ECMO therapy (p

MR lung volume in fetal congenital diaphragmatic hernia: logistic regression analysis--mortality and extracorporeal membrane oxygenation.

PURPOSE: To prospectively assess the results of logistic regression analysis that were based on magnetic resonance (MR) image fetal lung volume (FLV) measurements to predict survival and the corresponding need for extracorporeal membrane oxygenation (ECMO) therapy in fetuses with congenital diaphragmatic hernia (CDH) before and after 30 weeks gestation. MATERIALS AND METHODS: Written informed consent was obtained and the study was approved by the local research ethics committee. FLV was measured on MR images in 95 fetuses (52 female neonates, 43 male neonates) with CDH between 22 and 39 weeks gestation by using multiplanar T2-weighted half-Fourier acquired single-shot turbo spin-echo MR imaging. On the basis of logistic regression analysis results, mortality and the need for ECMO therapy were calculated for fetuses before and after 30 weeks gestation. RESULTS: Overall, higher FLV was associated with improved survival (P < .001) and decreasing probability of need for ECMO therapy (P = .008). Survival at discharge was 29.2% in neonates with an FLV of 5 mL, compared with 99.7% in neonates with an FLV of 25 mL. The corresponding need for ECMO therapy was 56.1% in fetuses with an FLV of 5 mL and 8.7% in fetuses with an FLV of 40 mL. Prognostic power was considerably lower before 30 weeks gestation. CONCLUSION: Beyond 30 weeks gestation, logistic regression analysis that is based on MR FLV measurements is useful to estimate neonatal survival rates and ECMO requirements. Prior to 30 weeks gestation, the method is not reliable and the FLV measurement should be repeated, particularly in fetuses with small lung volumes, before a decision is made about therapeutic options.

MR relative fetal lung volume in congenital diaphragmatic hernia: survival and need for extracorporeal membrane oxygenation.

PURPOSE: To retrospectively evaluate the accuracy of the absolute fetal lung volume (FLV) measured at magnetic resonance (MR) imaging and seven formulas for calculating relative FLV to predict neonatal survival and the need for extracorporeal membrane oxygenation (ECMO) in fetuses with congenital diaphragmatic hernia (CDH). MATERIALS AND METHODS: This retrospective study was approved by the research ethics committee, and informed consent was received from all mothers for previous prospective studies. In total, 68 fetuses with CDH were assessed by using MR image FLV measurement within 23-39 weeks gestation. The relative FLV was expressed as a percentage of the predicted lung volume calculated with biometric parameters according to seven formulas previously described in the literature. Applying the area under the curve (AUC), the various relative FLVs and the absolute FLV were investigated for their prognostic accuracy to predict neonatal survival and the need for ECMO therapy. RESULTS: All relative FLVs and the absolute FLV revealed a significant difference in mean lung volume between neonates who survived and neonates who did not survive (P = .001 to P < .001) and measurement accuracy was excellent for each method (AUC, 0.800-0.900). For predicting neonatal ECMO requirement, differences in FLVs were smaller but still significant (P = .05 to <.009) and measurement accuracy was acceptable throughout (AUC, 0.653-0.739). CONCLUSION: The various relative FLVs and the absolute FLV measured at MR planimetry are each highly valuable in predicting survival in fetuses with CDH. For predicting whether neonatal ECMO therapy is required, the accuracy of the absolute FLV (AUC, 0.68) and that of the relative FLVs (AUC, 0.653-0.739) was acceptable.

Reliability and validity of MR image lung volume measurement in fetuses with congenital diaphragmatic hernia and in vitro lung models.

PURPOSE: To prospectively assess the reliability of magnetic resonance (MR) image volume measurement in fetuses with congenital diaphragmatic hernia (CDH) and the reliability and validity of measurements in in vitro lung models. MATERIALS AND METHODS: This study was approved by the ethics committee, and informed consent was obtained. MR fetal lung volume (FLV) was measured in 40 consecutive fetuses with CDH by using half-Fourier acquired single-shot turbo spin-echo MR imaging and true fast imaging with steady-state precession at 24-36 weeks gestation (mean gestational age, 30.6 weeks +/- 3.5 [standard deviation]). Lung volumes were independently assessed in three orthogonal section planes by two experienced observers. Additionally, 28 in vitro lung models of defined volumes of 1-60 mL were evaluated the same way. To assess measurement validity and reliability, the intraclass correlation coefficient (ICC) and the Bland-Altman plot were used. RESULTS: The interobserver reliability was high for both the lung models and FLV measurements (ICC, 0.999 and 0.928, respectively). Measurement validity was also good, with a mean difference between the calculated volume and the true volume of 0.4 mL (95% confidence interval: 0.30, 0.48). Measurement reliability and validity did not depend, to any considerable degree, on imaging plane or sequence (ICC range, 0.878-0.999) or on total volume. CONCLUSION: The reliability and validity of MR volume measurements are high. The method is independent of the sequence and the imaging plane and can be performed with a very good interobserver agreement, even in small volumes.

Prediction of mortality and need for neonatal extracorporeal membrane oxygenation in fetuses with congenital diaphragmatic hernia: logistic regression analysis based on MRI fetal lung volume measurements.

OBJECTIVE: The purpose of this study was to use logistic regression analysis of prenatal MRI fetal lung volume measurements to calculate mortality and the need for extracorporeal membrane oxygenation (ECMO) therapy among fetuses with congenital diaphragmatic hernia (CDH). SUBJECTS AND METHODS: The fetal lung volume measurements of 65 fetuses with CDH were obtained between 32 and 34 weeks' gestation by means of MRI performed with multiplanar T2-weighted HASTE and true fast imaging with steady-state precession sequences. Logistic regression analysis was used to assess the prognostic value of the fetal lung volume measurements for prenatal prediction of fetal survival and need for neonatal ECMO. RESULTS: Fetal lung volume was a highly significant predictor of survival (p < 0.0001) and neonatal ECMO requirement (p = 0.0006). The mortality was 84% and the ECMO requirement 80% among fetuses with a lung volume of 5 mL. The mortality was 0.4% and the ECMO requirement 20% among patients with a fetal lung volume of 30 mL. CONCLUSION: Logistic regression analysis of MRI fetal lung volume measurements is highly valuable in predicting mortality among neonates with CDH, and it may help to estimate the need for neonatal ECMO. The method is feasible for facilitating parental guidance and may help in choosing postnatal therapeutic options, including ECMO therapy.

Comparison of five cluster validity indices performance in brain [18 F]FET-PET image segmentation using k-means.

PURPOSE: Dynamic [18 F]fluoro-ethyl-L-tyrosine positron emission tomography ([18 F]FET-PET) is used to identify tumor lesions for radiotherapy treatment planning, to differentiate glioma recurrence from radiation necrosis and to classify gliomas grading. To segment different regions in the brain k-means cluster analysis can be used. The main disadvantage of k-means is that the number of clusters must be pre-defined. In this study, we therefore compared different cluster validity indices for automated and reproducible determination of the optimal number of clusters based on the dynamic PET data. METHODS: The k-means algorithm was applied to dynamic [18 F]FET-PET images of 8 patients. Akaike information criterion (AIC), WB, I, modified Dunn's and Silhouette indices were compared on their ability to determine the optimal number of clusters based on requirements for an adequate cluster validity index. To check the reproducibility of k-means, the coefficients of variation CVs of the objective function values OFVs (sum of squared Euclidean distances within each cluster) were calculated using 100 random centroid initialization replications RCI100 for 2 to 50 clusters. k-means was performed independently on three neighboring slices containing tumor for each patient to investigate the stability of the optimal number of clusters within them. To check the independence of the validity indices on the number of voxels, cluster analysis was applied after duplication of a slice selected from each patient. CVs of index values were calculated at the optimal number of clusters using RCI100 to investigate the reproducibility of the validity indices. To check if the indices have a single extremum, visual inspection was performed on the replication with minimum OFV from RCI100 . RESULTS: The maximum CV of OFVs was 2.7 × 10-2 from all patients. The optimal number of clusters given by modified Dunn's and Silhouette indices was 2 or 3 leading to a very poor segmentation. WB and I indices suggested in median 5, [range 4-6] and 4, [range 3-6] clusters, respectively. For WB, I, modified Dunn's and Silhouette validity indices the suggested optimal number of clusters was not affected by the number of the voxels. The maximum coefficient of variation of WB, I, modified Dunn's, and Silhouette validity indices were 3 × 10-2 , 1, 2 × 10-1 and 3 × 10-3 , respectively. WB-index showed a single global maximum, whereas the other indices showed also local extrema. CONCLUSION: From the investigated cluster validity indices, the WB-index is best suited for automated determination of the optimal number of clusters for [18 F]FET-PET brain images for the investigated image reconstruction algorithm and the used scanner: it yields meaningful results allowing better differentiation of tissues with higher number of clusters, it is simple, reproducible and has an unique global minimum.

Genital invasion or perigenital spread may pose a risk of marginal misses for Intensity Modulated Radiotherapy (IMRT) in anal cancer.

BACKGROUND: While intensity modulated radiotherapy (IMRT) in anal cancer is feasible and improves high-dose conformality, the current RTOG/AGITG contouring atlas and planning guidelines lack specific instructions on how to proceed with external genitalia. Meanwhile, the RTOG-Protocol 0529 explicitly recommends genital sparing on the basis of specific genital dose constraints. Recent pattern-of-relapse studies based on conventional techniques suggest that marginal miss might be a potential consequence of genital sparing. Our goal is to outline the potential scope and increase the awareness for this clinical issue. METHODS: We present and discuss four patients with perigenital spread in anal cancer in both early and advanced stages (three at time of first diagnosis and one in form of relapse). Genital/perigenital spread was observed once as direct genital infiltration and thrice in form of perigenital lymphatic spread. RESULTS: We review the available data regarding the potential consequences of genital sparing in anal cancer. Pattern-of-relapse studies in anal cancer after conventional radiotherapy and the current use of IMRT in anal cancer are equivocal but suggest that genital sparing may occasionally result in marginal miss. An obvious hypothesis suggested by our report is that perigenital lymphovascular invasion might be associated with manifest inguinal N+ disease. CONCLUSIONS: Local failure has low salvage rates in recent anal cancer treatment series. Perigenital spread may pose a risk of marginal misses in IMRT in anal cancer. To prevent marginal misses, meticulous pattern-of-relapse analyses of controlled IMRT-series are warranted. Until their publication, genital sparing should be applied with caution, PET/CT should be used when possible and meeting genital dose constraints should not be prioritized over CTV coverage, especially (but not only) in stage T3/4 and N+ disease.

Quantitative and qualitative assessment of Yttrium-90 PET/CT imaging.

Yttrium-90 is known to have a low positron emission decay of 32 ppm that may allow for personalized dosimetry of liver cancer therapy with (90)Y labeled microspheres. The aim of this work was to image and quantify (90)Y so that accurate predictions of the absorbed dose can be made. The measurements were performed within the QUEST study (University of Sydney, and Sirtex Medical, Australia). A NEMA IEC body phantom containing 6 fillable spheres (10-37 mm ∅) was used to measure the 90Y distribution with a Biograph mCT PET/CT (Siemens, Erlangen, Germany) with time-of-flight (TOF) acquisition. A sphere to background ratio of 8:1, with a total (90)Y activity of 3 GBq was used. Measurements were performed for one week (0, 3, 5 and 7 d). he acquisition protocol consisted of 30 min-2 bed positions and 120 min-single bed position. Images were reconstructed with 3D ordered subset expectation maximization (OSEM) and point spread function (PSF) for iteration numbers of 1-12 with 21 (TOF) and 24 (non-TOF) subsets and CT based attenuation and scatter correction. Convergence of algorithms and activity recovery was assessed based on regions-of-interest (ROI) analysis of the background (100 voxels), spheres (4 voxels) and the central low density insert (25 voxels). For the largest sphere, the recovery coefficient (RC) values for the 30 min -2-bed position, 30 min-single bed and 120 min-single bed were 1.12 ± 0.20, 1.14 ± 0.13, 0.97 ± 0.07 respectively. For the smaller diameter spheres, the PSF algorithm with TOF and single bed acquisition provided a comparatively better activity recovery. Quantification of Y-90 using Biograph mCT PET/CT is possible with a reasonable accuracy, the limitations being the size of the lesion and the activity concentration present. At this stage, based on our study, it seems advantageous to use different protocols depending on the size of the lesion.

Diagnostic accuracy of 18F choline PET/CT using time-of-flight reconstruction algorithm in prostate cancer patients with biochemical recurrence.

PURPOSE: Image quality (IQ) of PET in voluminous body regions can be limited, which impairs the assessment of small metastatic lesions. Time-of-flight (TOF) reconstruction algorithm may deliver an increase of spatial resolution. The purpose of this study was to evaluate the impact of TOF on IQ, lesion detection rate, lesion volume (V) and SUVmax in F choline PET/CT of prostate cancer patients with biochemical recurrence compared to standard PET/CT reconstruction (standard). PATIENTS AND MATERIALS: During a period of 9 months, 32 patients with prostate cancer (mean [SD] age, 71 [7.8] years) and biochemical recurrence were included in this prospective institutional review board-approved study. Each patient underwent a state-of-the-art 3-dimensional F choline PET/CT. A total of 76 lesions were assessed by 2 board-certified nuclear medicine physicians and a third-year resident. Lesion volume and SUVmax of local recurrence, lymph nodes, and organ metastases were compared between TOF and standard. Image quality and lesion demarcation were rated according to a 5-point Likert-type scale. Interobserver agreement was assessed. RESULTS: Eight additional lesions were detected using TOF (SUVmax, 3.64 [0.95]; V, 0.58 cm [0.50]). Image quality was reduced (IQ standard, 1.28; TOF, 1.77; P < 0.01) in calculated TOF images, although quality of lesion demarcation was improved (lesion demarcation: standard, 1.66; TOF, 1.26; P < 0.01). SUVmax was significantly increased in TOF images (SUVmax standard, 6.9 [4.1]; TOF, 8.1 [4.1]; P < 0.01), whereas V did not show significant differences (V standard, 5.3 [10.4] cm; TOF, 5.4 [10.3] cm; P = 0.41). Interobserver agreement was good for combined ratings (1 + 2 and 3 + 4). CONCLUSIONS: Application of TOF seems to be of additional value to detect small metastatic lesions in patients with prostate cancer and biochemical recurrence, which may have further clinical implications for secondary treatment.

Impact of blood glucose, diabetes, insulin, and obesity on standardized uptake values in tumors and healthy organs on 18F-FDG PET/CT.

INTRODUCTION: Chronically altered glucose metabolism interferes with (18)F-FDG uptake in malignant tissue and healthy organs and may therefore lower tumor detection in (18)F-FDG PET/CT. The present study assesses the impact of elevated blood glucose levels (BGL), diabetes, insulin treatment, and obesity on (18)F-FDG uptake in tumors and biodistribution in normal organ tissues. METHODS: (18)F-FDG PET/CT was analyzed in 90 patients with BGL ranging from 50 to 372 mg/dl. Of those, 29 patients were diabetic and 21 patients had received insulin prior to PET/CT; 28 patients were obese with a body mass index >25. The maximum standardized uptake value (SUV(max)) of normal organs and the main tumor site was measured. Differences in SUV(max) in patients with and without elevated BGLs, diabetes, insulin treatment, and obesity were compared and analyzed for statistical significance. RESULTS: Increased BGLs were associated with decreased cerebral FDG uptake and increased uptake in skeletal muscle. Diabetes and insulin diminished this effect, whereas obesity slightly enhanced the outcome. Diabetes and insulin also increased the average SUV(max) in muscle cells and fat, whereas the mean cerebral SUV(max) was reduced. Obesity decreased tracer uptake in several healthy organs by up to 30%. Tumoral uptake was not significantly influenced by BGL, diabetes, insulin, or obesity. CONCLUSIONS: Changes in BGLs, diabetes, insulin, and obesity affect the FDG biodistribution in muscular tissue and the brain. Although tumoral uptake is not significantly impaired, these findings may influence the tumor detection rate and are therefore essential for diagnosis and follow-up of malignant diseases.