Combined measurement of tumor perfusion and glucose metabolism for improved tumor characterization in advanced cervical carcinoma. A PET/CT pilot study using [15O]water and [18F]fluorodeoxyglucose.

BACKGROUND AND PURPOSE: The aim of this pilot study was (1) to evaluate the combination of [(18)F]fluorodeoxyglucose (FDG) and [(15)O]water for detection of flow-metabolism mismatch in advanced cervical carcinomas, i.e., increased glycolysis at low blood flow, as a possible parameter for prediction of response to treatment, and (2) to propose a method for automated quantification of its spatial extent. PATIENTS AND METHODS: The study retrospectively included 10 women with advanced cervical carcinoma in whom PET with both FDG and [(15)O]water had been performed prior to therapy. The metabolically active tumor volume was delineated automatically in the FDG images. For computation of the regional blood flow in the tumor, a recovery corrected image-derived arterial input function was used. A tumor voxel was classified as mismatched when the voxel SUV of FDG was larger than the median tumor SUV and the voxel perfusion (K1) was smaller than the median perfusion. The absolute mismatch volume (aMMV) was defined as the volume of all mismatched voxels in ml, and the relative mismatch volume (rMMV) as the ratio of the aMMV to the metabolic tumor volume in percent. RESULTS: The tumors were quite heterogeneous with respect to both FDG uptake and perfusion. The aMMV clustered into 2 groups: "large aMMV" ≥ 10 ml in 40 % of patients and "small aMMV" ≤ 5 ml in 60 % of patients. The rMMV ranged from 12.7-24.9 %. There was no correlation between rMMV and metabolic tumor volume. There was a tendency (p = 0.126) for an association between rMMV and histological grading, rMMV being about 20 % higher in G3 than in G2 tumors. rMMV did not correlate with SUV or perfusion. CONCLUSION: These results suggest that combined PET with FDG and [(15)O]water allows detection and quantitative characterization of flow-metabolism mismatch in advanced cervical carcinomas.

Topographic analysis and evaluation of anatomical landmarks for placement of central venous catheters based on conventional chest X-ray and computed tomography.

BACKGROUND: Positioning central venous catheters (CVCs) in the proper part of the superior vena cava (SVC) is difficult. The aim of this exploratory study was to analyse topographic relationships of the extrapericardial SVC using chest X-ray (CXR) and computed tomography (CT). This included an appraisal of rules for optimal CVC tip placement. METHODS: We retrospectively evaluated 100 patients with CVCs who underwent bedside CXR and CT on the same day. Distances between the sternoclavicular joint (SCJ), tracheal carina, SVC origin, pericardial reflection, and CVC tip were analysed on CT and, if visible, on CXR. These measurements served to locate the extrapericardial SVC in relation to anatomical landmarks. Different strategies for CVC tip positioning were evaluated. RESULTS: The mean (standard deviation) extrapericardial length of the SVC was 26 (12) mm. The average position of the pericardial reflection was 5 mm below the carina (range, 29 mm below to 25 mm above). In our patient population, the best results in terms of tip positions in the extrapericardial SVC would have been achieved by using 85% of the SCJ-to-carina distance (in 86%) or by positioning the CVC tip 9 mm above the carina (in 84% of patients). CONCLUSIONS: The extrapericardial part of the SVC varies considerably in length and position, and rules of thumb based on anatomical landmarks should be used cautiously. In our series, using 85% of the SCJ-to-carina distance or placing the CVC tip 9 mm above the carina would have resulted in a high percentage of positions in the extrapericardial SVC.

Evaluation of interim PET response criteria in paediatric Hodgkin's lymphoma--results for dedicated assessment criteria in a blinded dual-centre read.

BACKGROUND: The aim of this study was to evaluate the use and reliability of the new positron emission tomography (PET)-based response criteria for interim positron emission tomography (iPET) in patients with paediatric Hodgkin's lymphoma (pHL). Particular emphasis was put on interobserver variability and on identification of a visual cut-off defining patients with very low risk for relapse. PATIENTS AND METHODS: The iPET scans of 39 pHL patients were evaluated in two independent centres by two PET-experienced specialists in nuclear medicine (blinded read, centre consensus) each. The iPET scans were interpreted using a 5-point scale and were compared with the outcome. Cohen's kappa-test (κ) was used to analyse the interobserver agreement. RESULTS: Concordant ratings were assessed in 19 patients with iPET-negative findings, in 11 patients with iPET-positive findings and in 2 patients with inconclusive ratings. A 'substantial agreement' between attended centres was achieved (κ = 0.748). All patients suffering relapse were concordantly identified, taking mediastinal blood pool structures (MBPS) as visual cut-off between PET-positive and PET-negative findings, respectively. All pHL patients with uptake lower than or equal to MBPS remained in complete remission. CONCLUSION(S): The iPET interpretation assured low interobserver variability. High sensitivity for identification of pHL patients suffering relapse is achieved if [18F]-fluorodeoxyglucose uptake above the MBPS value is rated as a PET-positive finding.

Predictive Value of Asphericity in Pretherapeutic [111In]DTPA-Octreotide SPECT/CT for Response to Peptide Receptor Radionuclide Therapy with [177Lu]DOTATATE.

PURPOSE: The purpose of this study was to assess the value of the spatial heterogeneity of somatostatin receptor (SSR) volume, quantified as asphericity (ASP), and to predict response to peptide receptor radionuclide therapy (PRRT) in patients with metastatic gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN). PROCEDURES: From June 2011 to May 2013, patients suffering from GEP-NEN who underwent pretherapeutic [111In-DTPA0]octreotide scintigraphy (Octreoscan®) prior to [177Lu-DOTA0-Tyr3]octreotate ([177Lu]DOTATATE)-PRRT were enrolled in this retrospective evaluation. SSR expression in 20 NEN patients was qualitatively and quantitatively assessed using the Krenning score, the metastasis to liver uptake ratio (M/L ratio), and ASP at baseline. Response to PRRT was evaluated based on lesions, which were classified as responding lesions (RL) and non-responding lesions (NRL) after 4- and 12-month follow-ups. The values of the Krenning score, M/L ratio, and ASP for response prediction were compared by using the Mann-Whitney U test, Kruskal-Wallis test, and receiver operating characteristic (ROC) curves. RESULTS: Seventy-seven metastases (liver, n = 40; lymph node, n = 24; bone, n = 11; pancreas, n = 2) showed SSR expression. A higher ASP level was significantly associated with poorer response at both time points. ROC analyses revealed the highest area under the curve (AUC) for discrimination between RL and NRL for ASP after 4 months (AUC 0.97; p = 0.019) and after 12 months (AUC 0.96; p < 0.001), followed by the Krenning score (AUC 0.74; p = 0.082 and AUC 0.85; p < 0.001, respectively) and M/L ratio (AUC 0.77; p = 0.107 and AUC 0.82; p < 0.001). The optimal cutoff value for ASP was 5.12 % (sensitivity, 90 %; specificity, 93 %). CONCLUSION: Asphericity of SSR-expressing lesions in pretherapeutic single-photon emission computed tomography with integrated computed tomography (SPECT/CT) is a promising parameter for predicting response to PRRT in gastroenteropancreatic neuroendocrine neoplasms.

Tumor cell uptake of 99mTc-labeled 1-thio-ß-D-glucose and 5-thio-D-glucose in comparison with 2-deoxy-2-[18F]fluoro-D-glucose in vitro: kinetics, dependencies, blockage and cell compartment of accumulation.

PURPOSE: This study was conducted to investigate the capacity of (99m)Tc-labeled 1-thio-ß-D-glucose ((99m)Tc-1-TG) and 5-thio-D-glucose ((99m)Tc-5-TG) to act as a marker for glucose metabolism in tumor cells in vitro. PROCEDURES: We investigated the cellular uptake of (99m)Tc-1-TG, (99m)Tc-5-TG, and 2-deoxy-2-[(18)F]fluoro-D-glucose((18)F-FDG) in a human colorectal carcinoma and human lung adenocarcinoma cell line (HCT-116, A549) at different time points and varying glucose/insulin concentrations and under transporter blockage by cytochalasin-B and phloretin. Cell compartment analysis was performed. RESULTS: A significant uptake and time dependency thereof, a significant uptake dependency on glucose and insulin and a significant uptake inhibition by cytochalasin-B for (99m)Tc-1-TG and (99m)Tc-5-TG, was shown. Albeit substantial, the uptake was less pronounced in (99m)Tc-1-TG and (99m)Tc-5-TG compared with (18)F-FDG. (99m)Tc-1-TG and (99m)Tc-5-TG showed a higher accumulation in the cell membranes compared with (18)F-FDG. CONCLUSION: Tc-1-TG and (99m)Tc-5-TG showed an uptake in vitro with glucose analog characteristics but with membranous accumulation. Tumor imaging should be investigated in an animal model.

Morphological analysis and differentiation of benign cystic neoplasms of the pancreas using computed tomography and magnetic resonance imaging.

PURPOSE: To evaluate morphologic characteristics and establish a standardized diagnostic algorithm to differentiate benign cystic pancreatic tumors (CPTs) in non-pancreatitis patients using multidetector computed tomography (CT) and magnetic resonance imaging (MRI). MATERIALS AND METHODS: Patients with histopathologically proven CPTs who had undergone MRI and/or CT and subsequent tumor resection in our institution were retrospectively identified. Images were analyzed for morphology and enhancement patterns by three independent blinded observers. Preoperative image findings were correlated with histopathological results. Based on the evaluated morphologic parameters, a standardized diagnostic algorithm was designed to help characterize the lesions. RESULTS: A total of 62 consecutive patients with 64 CPTs were identified from the surgical database (21 intraductal papillary mucinous neoplasms; 10 mucinous cystic neoplasms; 12 serous microcystic adenomas; 3 serous oligocystic adenomas; 6 solid pseudopapillary tumors; 12 neuroendocrine neoplasms). The overall averaged accuracy for the 3 observers was 89.9 % for CT and 93.1 % for MRI with increasing overall accuracy in relation to the experience of the observer (88.2 %, 91.5 %, and 93.8 %, respectively). Overall, the generalized kappa value was 0.69 (CT, 0.64; MRI, 0.76); p < 0.001). The accuracy of the standardized diagnostic algorithm was 91.1 %. CONCLUSION: It is possible to characterize benign CPTs with MRI and CT, while MRI appears to be superior to CT. Diagnostic accuracy depends on the observer's experience. The standardized algorithm can aid in the differential diagnosis but still needs to be tested in other patient populations.

Interim PET response criteria in paediatric non-Hodgkin's lymphoma. Results from a retrospective multicenter reading.

AIM: To evaluate the use and reliability of the PET-based response criteria for interim PET (iPET) in terms of interobserver variability in pediatric and adolescent patients suffering from non-Hodgkin´s lymphoma (NHL). Particular attention was given to the identification of visual cutoff to separate patients with a favourable outcome. PATIENTS, METHODS: Retrospective analysis of PET-datasets of 18 children and adolescents suffering from NHL who underwent iPET after two cycles of chemotherapy for response assessment. Datasets were evaluated and rated in three independent review centers (RC) (blinded-read, intra-center consensus) using a visual 5-point response scale. Ratings were compared to clinical outcome. Pairwise interobserver agreement was analysed with Cohen's kappa-test (κ). Overall agreement (between attended RCs) was assessed with Fleiss' κ-test. RESULTS: Four patients suffered relapse (early, n = 2; late, n = 2). Per region analyses on interobserver variability revealed a "substantial" agreement (Fleiss' κ = 0.618). Per patient analyses revealed concordant iPET-ratings in eight patients: iPET-negative (iPET-), n = 5; iPET-positive (iPET+), n = 2; iPET-inconclusive (iPET±), n = 1. Discordant ratings were found in the remaining patients. Patients with early relapse were concordantly identified using mediastinal blood pool structures (MBPS, score ≥ 3) as visual cutoff between iPET+ or iPET-, respectively. However, patients with late relapse were not concordantly identified taking the MBPS as visual cutoff. CONCLUSION: The iPET interpretation using a dedicated PET-based response scale assured a low interobserver variability in per-region but not in per-patient analyses in a multicenter read. Using a sensitive read out (iPET+, score ≥ 3) a reliable identification of patients suffering relapse was limited to those with early relapse.

[Change in health-related quality of life and change in clinical symptoms after uterine artery embolization in patients with symptomatic adenomyosis uteri - evaluation using a standardized questionnaire]. / Änderung der gesundheitsbezogenen Lebensqualität und der klinischen Beschwerdestärke nach Uterusarterienembolisation bei symptomatischer Adenomyosis uteri evaluiert mittels standardisiertem Fragebogen.

AIM: To evaluate the clinical response of uterine artery embolization (UAE) in women with symptomatic uterine adenomyosis by comparing health-related quality of life and symptom severity before and after UAE using a standardized questionnaire. MATERIAL AND METHODS: This longitudinal study at two time points included 17 patients with a median age of 47.1 years with symptomatic uterine adenomyosis (n = 7 pure adenomyosis; n = 10 with concomitant fibroids). The diagnosis was based on clinical symptoms and magnetic resonance imaging (MRI) criteria. Data on health-related quality of life and severity of symptoms before and after UAE were obtained by the standardized "Uterine Fibroid Symptom and Quality of Life" (UFS-QOL) questionnaire and correlated in the following. Treatment failure was defined as the need for a second invasive procedure because of recurrent symptoms or persistent symptoms after UAE. RESULTS: The median interval between the evaluation of the UFS-QOL questionnaire before and after UAE was 46.0 months. 70.6 % (12/17; 95 % confidence interval 44.0 %  - 88.6 %) of the patients had therapy response with a significant improvement of health-related quality of life and clinical symptoms (p-value = 0.002). The therapy failure rate was 29.4 % (5/17; 95 % confidence interval 11.4 %  - 56.0 %). One patient underwent dilatation and curettage and four patients underwent hysterectomy because of therapy failure. CONCLUSION: UAE to treat symptomatic adenomyosis uteri can significantly improve the health-related quality of life and clinical symptoms. However, therapy failure is possible in up to one-third of patients.

MR imaging findings in flexed abducted supinated (FABS) position and clinical presentation following refixation of distal biceps tendon rupture using bioabsorbable suture anchors.

PURPOSE: To correlate MRI findings after suture anchor repair of distal biceps tendons with symptoms. MATERIALS AND METHODS: 24 men with 25 distal biceps tendon ruptures (one bilateral) treated with suture anchor repair were retrospectively included. Follow-up after a mean of 31 months (range, 12-74) included clinical examination and MRI. The pain level and flexion strength compared to the uninvolved arm were recorded. MRI was performed at 1.5 T obtaining FABS position images (both elbows in 7 patients) and evaluated for artifacts, signal abnormalities, and rerupture by two experienced readers in consensus and blinded to symptoms. Pain and loss of flexion strength>20% were tested against MRI findings as dichotomous data using Fisher's exact chi-square tests (p<0.05). Crosssectional areas of operated and uninvolved tendons were measured and evaluated with the Wilcoxon signed rank test (p<0.05). RESULTS: FABS views enabled good evaluation in 96% of tendons. Rerupture was present in 3 of 25 elbows. Tendinous signal increase was seen in 59% of intact tendons. We found activity-related pain or pain at rest in 32% and a loss of flexion strength in 27 % of these cases. Testing revealed no significant correlation for any of the MRI features with any of the clinical parameters (p>0.05). There was a 2.7-fold mean increase of the tendon cross-sectional area on the repaired side compared to the uninvolved contralateral tendon (p=0.02). CONCLUSION: We found good MRI visualization of postoperative tendons, but no correlation between symptoms and MRI signal abnormalities or rerupture. The increase in caliber of the repaired tendon might promote an impingement in pronation.

MRI versus bone scintigraphy. Evaluation for diagnosis and grading of stress injuries.

AIM: This study was set up to determine the value of magnetic resonance imaging (MRI) and bone scintigraphy (BS) for the diagnosis of stress injuries in athletes, and furthermore to assess reliability and prediction of healing time. PATIENTS, METHODS: Imaging data was analyzed retrospectively from 28 athletes who had received MRI and BS examinations for suspected stress injuries. MRI- and BS-data were rated by three specialists each in a blinded read, using a 5-point score (i.e. 0-4: inconspicuous to high-grade stress fracture). An interdisciplinary expert truth-panel set the reference standard. Standard statistical parameters, Fleiss' kappa (κ), and group comparisons were calculated. RESULTS: The sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) for detection of stress injuries were 71.4%, 85.7%, 78.6%, 83.3% and, 75.0%, for MRI and 92.9%, 73.8%, 83.3%, 78.0% and, 91.2% for BS, respectively. Interobserver reliability for the diagnosis of a stress injury was κ = 0.9 for BS and κ = 0.85 for MRI. Mean healing times of mild (grades 1 and 2) and severe (grades 3 and 4) stress injuries were 88 days (d) versus 142d for BS and 57d versus 116d for MRI. No significant difference in healing time could be shown. CONCLUSIONS: MRI and BS reliably detect stress injuries. MRI is to be recommended as the primary imaging modality due to its potential for assessment of differential diagnoses and the lack of radiation exposure, the value of BS lies in the exclusion of stress fractures after inconclusive MRI examinations.

Qualitative JPEG 2000 compression in digital mammography - evaluation using 480 mammograms of the CDMAM phantom.

PURPOSE: The DICOM standard supports both quantitative and qualitative lossy compression of mammograms.The purpose of this study was to investigate qualitative JPEG 2000 lossy compression and how different factors such as object thickness, radiation dose, and lossy compression levels affect image quality. MATERIALS AND METHODS: The CDMAM phantom Artinis 3.4 was radiographed with 4 different object thicknesses and 5 different doses. The images were compressed at 10 different compression levels. The image quality was assessed by the software interpolated IQFinv value. RESULTS: Lossy 90 resulted in 89 % data reduction, lossy 70 in 95 % data reduction and lossy 60 in 96 % data reduction. At higher compression levels (lossy 30), the resulting image quality ranged from 80 - 36 %, and at low compression levels (lossy 90), it ranged from 89 - 93 %. The object thickness was found to significantly interact with the compression level with regard to the resulting image quality: a higher object thickness resulted in increasingly poor image quality at increasing compression levels (p < 0.05). CONCLUSION: Higher qualitative JPEG 2000 compression levels contribute only little additional data reduction, while the resulting image quality cannot be reliably predicted. Factors affecting image quality such as radiation dose and object thickness should be taken into account when performing image compression. Large object thicknesses should be compressed with caution because the loss of image quality is greater when intelligent data compression algorithms are used.

Volume measurement of liver metastases using multidetector computed tomography: comparison of lesion diameter and volume segmentation - a phantom study.

PURPOSE: To compare lesion volume determination by applying diameter measurement and three different segmentation algorithms at different slice thicknesses reconstructed from computed tomography (CT) of a phantom model for hepatic colorectal metastases. MATERIALS AND METHODS: Based on CT attenuation measurements obtained retrospectively from 20 patients with colorectal liver metastases, a phantom model was designed with a sponge soaked with a dilution of contrast agent and 6 embedded polyamide spheres (diameter, 8 - 30 mm) to simulate the contrast behavior of liver metastases. CT scans were obtained and reconstructed at different slice thicknesses (0.625/1.25/2.5/3.75 mm; increment, 1). One observer performed software-aided volume determination using the maximum diameter, manual segmentation, seed point method, and threshold method six times for each lesion in a randomized order. Statistical analysis revealed the absolute and relative differences from the actual lesion volumes and the intraobserver differences as well as the influence of slice thickness for each method. RESULTS: The mean relative differences of the seed point method (1.2 - 5.9%) and manual segmentation (2.6 - 4.9%) were significantly lower than the threshold method (5.4 - 12.8%) and diameter measurement (12.3 - 18.5%; p < 0.01). Volume determination by manual segmentation and the seed point method benefited from the use of thin-slice CT datasets. The intraobserver variation was lowest when using the manual segmentation (1.5 - 3.3%) and the seed point method (2.2 - 3.9%; p < 0.001). CONCLUSION: Manual segmentation and the seed point method for thin CT slices were the methods with the lowest volume differences and intraobserver variation.