Different narcotic gases and concentrations for immobilization of ostrich embryos for in-ovo imaging.

In-ovo imaging using avian eggs has been described as a potential alternative to animal testing using rodents. However, imaging studies are hampered by embryonal motion producing artifacts. This study aims at systematically comparing isoflurane, desflurane and sevoflurane in three different concentrations in ostrich embryos. Biomagnetic signals of ostrich embryos were recorded analyzing cardiac action and motion. Ten groups comprising eight ostrich embryos each were investigated: Control, isoflurane (2%, 4%, and 6%), desflurane (6%, 12%, and 18%) and sevoflurane (3%, 5%, and 8%). Each ostrich egg was exposed to the same narcotic gas and concentration on development day (DD) 31 and 34. Narcotic gas exposure was upheld for 90 min and embryos were monitored for additional 75 min. Toxicity was evaluated by verifying embryo viability 24 h after the experiments. Initial heart rate of mean 148 beats/min (DD 31) and 136 beats/min (DD 34) decreased over time by 44-48 beats/minute. No significant differences were observed between groups. All narcotic gases led to distinct movement reduction after mean 8 min. Embryos exposed to desflurane 6% showed residual movements. Isoflurane 6% and sevoflurane 8% produced motion-free time intervals of mean 70 min after discontinuation of narcotic gas exposure. Only one embryo death occurred after narcotic gas exposure with desflurane 6%. This study shows that isoflurane, desflurane and sevoflurane are suitable for ostrich embryo immobilization, which is a prerequisite for motion-artifact free imaging. Application of isoflurane 6% and sevoflurane 8% is a) safe as no embryonal deaths occurred after exposure and b) effective as immobilization was observed for approx. 70 min after the end of narcotic gas exposure. These results should be interpreted with caution regarding transferability to other avian species as differences in embryo size and incubation duration exist.

[Selective internal radioembolization in nonresectable hepatocellular carcinoma]. / Selektive interne Radioembolisation beim nichtresektablen hepatozellulären Karzinom.

INTRODUCTION: The role of selective internal radioembolization (SIRT) in the treatment of hepatocellular carcinoma (HCC) is currently unclear. MATERIALS AND METHODS: We investigated 52 patients with nonresectable HCC in cirrhosis who underwent SIRT at the Department of General, Visceral and Vascular Surgery in co-operation with the Department of Nuclear Medicine and the Institute of Diagnostic and Interventional Radiology between April 2011 and October 2015. RESULTS: In five patients, SIRT was employed for bridging to liver transplantation. In patients who had undergone pre-treatment with SIRT, histological examination of the explanted livers showed extensive tumor necrosis in the targeted areas with only minor remnant vital tissue at the margins. Four of the patients who underwent SIRT as local bridging treatment are tumor-free after transplantation. In the 47 palliatively treated patients, a total of 76 radioembolizations were performed. The observed 1­ and 2­year survival rates in these patients were 58 and 29 %, respectively, after the first SIRT. In the multivariate analysis of the observed survival, AFP before the first SIRT >30ng/ml, time interval of <12 months between the initial diagnosis and the first SIRT, largest tumor diameter >5 cm and portal vein thrombosis were independent negative prognostic factors. In the multi-variate analysis, the time to progression was independently influenced only by the AFP level before the first SIRT. In addition to standard treatment with transarterial chemoembolization (TACE), SIRT is feasible in nonresectable HCC, in particular with portal vein thrombosis, with identical results, less interventions and few side effects.

Enhancing 18F-FDG-PET/CT analysis in lung cancer patients. Is CT-CT image fusion helpful in predicting pleural involvement? A pilot study.

AIM: To retrospectively evaluate the feasibility and value of CT-CT image fusion to assess the shift of peripheral lung cancers with/-out chest wall infiltration, comparing computed tomography acquisitions in shallow-breathing (SB-CT) and deep-inspiration breath-hold (DIBH-CT) in patients undergoing FDG-PET/CT for lung cancer staging. METHODS: Image fusion of SB-CT and DIBH-CT was performed with a multimodal workstation used for nuclear medicine fusion imaging. The distance of intrathoracic landmarks and the positional shift of tumours were measured using semi-transparent overlay of both CT series. Statistical analyses were adjusted for confounders of tumour infiltration. Cutoff levels were calculated for prediction of no-/infiltration. RESULTS: Lateral pleural recessus and diaphragm showed the largest respiratory excursions. Infiltrating lung cancers showed more limited respiratory shifts than non-infiltrating tumours. A large respiratory tumour-motility accurately predicted non-infiltration. However, the tumour shifts were limited and variable, limiting the accuracy of prediction. CONCLUSION: This pilot fusion study proved feasible and allowed a simple analysis of the respiratory shifts of peripheral lung tumours using CT-CT image fusion in a PET/CT setting. The calculated cutoffs were useful in predicting the exclusion of chest wall infiltration but did not accurately predict tumour infiltration. This method can provide additional qualitative information in patients with lung cancers with contact to the chest wall but unclear CT evidence of infiltration undergoing PET/CT without the need of additional investigations. Considering the small sample size investigated, further studies are necessary to verify the obtained results.

Real-time ultrasound and freehand-SPECT. Experiences with sentinel lymph node mapping.

UNLABELLED: Aim of this work is to report first experiences of the feasibility and applicability of a hybrid freehandSPECT/ultrasound (fh-SPECT/US) imaging concept, with regard to SLN imaging, in patients with breast cancer and malignant melanoma. PATIENTS, METHODS: 18 patients with breast cancer or malignant melanoma received standard SLN scintigraphy. Following this, fh-SPECT using declipse®SPECT (SurgicEye, Munich, Germany) was performed, a handheld-gamma camera-based method to visualize activity distribution within a region of interest as a cross-sectional data set. These data were transferred to an ultrasound device and sensor-navigated ultrasound was performed combining fh-SPECT data with ultrasound images, displaying superimposed images. Quality of fh-SPECT and co-registration accuracy was assigned to one of four categories and occurrence of artefacts was assessed. RESULTS: In 4/18 examinations, there was a no deviation regarding co-registration of both data sets. For 9/18 patients, there was a deviation of <1 cm (mean 0.7±0.3 cm, range 0.3-1.0 cm). For 3/18 patients, a deviation >1 cm was present (mean 1.7±0.3 cm, range 1.5-2.0 cm). In 2/18 examinations no lymph node was found in the region of highest activity. Fh-SPECT reconstruction artifacts occurred in 6/18 examinations. CONCLUSION: The fusion imaging concept combining SLN information with ultrasound images presented here proves to be feasible and technically successful. However, significant technical limitations were shown in fh-SPECT quality and fusion precision. Subject to technical optimisation of SPECT quality and co-registration, a meaningful contribution to the preoperative planning of lymph node therapy is imaginable. Thus, fundamentally a preoperative histological examination by fh-SPECT/US-guided biopsy is possible.

Real-time handheld emission spot allocator (rthESA) for simultaneous fusion imaging with ultrasound.

OBJECTIVES: First, to report on initial experiences and technical parameters of a newly developed real-time handheld emission spot allocator (rthESA), and second, to report on the simultaneous acquisition of rthESA and US data as rthESA/US fusion images. METHODS: The rthESA consisted of five semiconductor-detectors arranged in alternate position in two rows. This design allowed the examination of focal activities in the same plane as US. The signals were interpreted by an ad hoc software and the real-time allocation of spot radiation sources within air- and water phantoms was investigated for (99m)Tc, 131I, and 18F. A compact US probe was fixed in plane with the rthESA and connected to a standard US equipment. Experiments with a liver phantom were performed to verify the integration of (99m)Tc-rthESA data and US images. RESULTS: The allocation proved to be successful for all radionuclides. The system showed a noticeable performance latency, most pronounced for positions far from the detector (1 cm distance: 0.7 ± 0.5 s; 4 cm distance: 6.1 ± 3.2 s). Within the liver phantom, the rthESA enabled the correct allocation of a spot radiation source within a live US image. CONCLUSIONS: The rthESA allowed an exact localization of spot radiation sources in single plane, with additional consideration of the distance from the detector, leading to real-time allocation and simultaneous overlay with US images. In spite of clear technical limitations in need of further development, this proof-of-concept study shows that this hybrid detector has the potential to provide integrated simultaneous nuclear medicine and US images.

Early detection of disease progression after palliative chemotherapy in NSCLC patients by (18)F-FDG-PET.

AIM: We investigated whether 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) is capable of detecting renewed disease progression earlier than computed tomography (CT) in patients with inoperable non-small cell lung cancer (NSCLC) who have undergone chemotherapy as part of a palliative treatment plan. PATIENTS, METHODS: 18 patients were studied retrospectively. Three FDG-PET/CT scans for initial and follow-up diagnostic purposes were evaluated. Palliative chemotherapy was administered between the first FDG-PET/CT scan (t0) and the second (t1), followed by a treatment-free interval between the second FDG-PET/CT scan (t1) and the third (t2). Maximum standardized uptake values (SUVmax) and largest diameters of lesions were determined for PET scans and the corresponding CTs. Lesion-based and patient-based assessments were performed, as were assessments according to RECIST/PERCIST. RESULTS: 82 lesions were identified in 18 patients. In interval t1-t2, the increase in diameter in the lesion-based evaluation was 5.0% (non-significant), while the patient-based evaluation showed a non-significant reduction of 2.8%. Considering PET, both the lesion-based and patient-based evaluations found a significant increase in SUVmax by a median of 30.4 % and 45.8 %, respectively. PERCIST criteria at time point t2 identified ten more patients with progression than did RECIST. CONCLUSION: In patients with NSCLC, renewed progression during the treatment-free interval after palliative chemotherapy can be detected earlier with PET than with CT. Thus, FDG-PET appears to be a useful diagnostic imaging procedure regarding this aspect. Its clinical relevance should be investigated in further studies.

[Joint swelling, reversible arm paresis, and elevated serum IgG4 in a 55-year-old man]. / Gelenkschwellungen, reversible Armparese und erhöhtes Serum-IgG4 bei einem 55-jährigen Patienten.

Only described in the last 10 years, IgG4-related disease is a fibroinflammatory disorder characterized by tumorous lesions with dense lymphoplasmacytic infiltration by IgG4-positive plasma cells and often elevated concentration of serum IgG4. In this paper, we present a male patient with this disease involving the lymph nodes and possibly the joints and kidneys. Infiltration of lymph node tissue with IgG4-positive plasma cells was demonstrated. The general condition of the patient improved considerably by immunosuppressive therapy.

The influence of radioiodine therapy on the number of circulating epithelial cells (CEC) in patients with differentiated thyroid carcinoma - a pilot study.

GOAL: The aim of this pilot study was to investigate the changes of circulating epithelial cells in the blood of patients with differentiated thyroid cancer after radioiodine-therapy with I-131. METHODS: The cells were detected by fluorescence-microscopy via the epithelial-cell-adhesion-molecule (EpCAM), a molecule described to be over-expressed in most carcinoma tissues and also present on circulating cells deriving from primary site. Epithelial cells were assessed before radioiodine-therapy, as well as 2 days, 14 days, and 3 months after therapy. 2 patient groups were examined: 1) patients with thyroid cancer receiving a first radioiodine-therapy after thyroidectomy (RITfirst, n=13), and 2) patients with thyroid cancer in need of repeated radioiodine-therapy due to local or metastatic recurrences (RITrep, n=15). Circulating epithelial cell changes were correlated to changes of serum-thyroglobulin and to clinical response evaluated 3 months after therapy. RESULTS: Patients with an early decrease of cells after radioiodine-therapy (RITfirst 7/13; RITrep 2/15) showed an increase of serum-thyroglobulin in most of the cases (RITfirst 5/7; RITrep 2/2). In the RITrep group, a decrease in cell counts 2 days after radioiodine-therapy indicated a clinical response in 90% of the cases. CONCLUSIONS: This study indicates that the number of circulating epithelial cells in differentiated thyroid cancer undergo changes in response to radioiodine-therapy. The destruction of cells through radioiodine-therapy may induce a short-term release of thyroglobulin in the blood. A clear relationship between the clinical outcome and the cell changes could not be found, but early cell decreases may help identifying patients more likely to respond to radioiodine-therapy.

3D ultrasonography is as accurate as low-dose CT in thyroid volumetry.

AIM: The purpose of this study was to compare thyroid volumetry by three-dimensional mechanically swept ultrasonography (3DmsUS) and low-dose computed tomography (ldCT). PATIENTS, METHODS: 30 subjects referred for radioiodine therapy of benign thyroid diseases were subjected to 3DmsUS and ldCT. A prerequisite of 3DmsUS analyses was that the scans had to capture the entire thyroid, excluding therefore cases with a very large volume or retrosternal portions. The 3DmsUS data were transformed into a DICOM format, and volumetry calculations were performed via a multimodal workstation equipped with standard software for cross-sectional imaging. Volume was calculated applying both the ellipsoid model and a manually tracing method. Statistical analyses included 95% confidence intervals (CI) of the means and limits of agreement according to Bland and Altman, the latter including 95% of all expected values. RESULTS: Volumetric measurements by 3DmsUS and ldCT resulted in very high, significant correlation coefficients, r = 0.997 using the ellipsoid model and r = 0.993 with the manually tracing method. The mean relative differences of the two imaging modalities proved very small (-1.2±4.0% [95% CI -2.62; 0.28] using the ellipsoid model; -1.1±5.2% [95% CI -2.93; 0.80] using the manually tracing method) and the limits of agreement sufficiently narrow (-9.1% to 6.8%; -11.3% to 9.2%, respectively). CONCLUSION: For moderately enlarged thyroids, volumetry with 3DmsUS proved comparable to that of ldCT, irrespective of whether the ellipsoid model or the manually tracing method was applied. Thus, 3DmsUS qualifies as a potential alternative to ldCT, provided that the organ is completely accessible. The use of a standard workstation for cross-sectional imaging with routine software did not prove problematic.

Early dynamic 18F-FDG PET/CT to diagnose chronic osteomyelitis following lower extremity fractures. A pilot study.

AIM: The study investigates whether early dynamic PET/CT (edPET/CT) using 18F-fluorodeoxyglucose (FDG) discriminates between affected versus non-affected sites in patients with complicated, protracted fracture healing and suspected COM in the lower extremities. PATIENTS, METHODS: In nine consecutive patients (1 woman, 8 men; age 54 ± 13 years), before standard late FDG-PET/CT, altogether 10 edFDG-PET/CT examinations were performed in list mode over 5 min starting with radiopharmaceutical injection. Eight consecutive time intervals (frames), four 15-s, then four 60-s, were reconstructed. For every patient, several volumes-of-interest were selected. To measure early FDG influx and accumulation, maximum and mean ed standardized uptake values (respectively, edSUVmax, edSUVmean) were calculated in each volume-of-interest during each frame. Results were compared between affected and non-affected (contralateral) bone. RESULTS: Starting in the 31-45s frame, the affected bone area showed significantly higher edSUVmax and edSUVmean than did the healthy contralateral region. In conventional PET/CT, affected bone areas also significantly differed from non-affected contralateral regions. CONCLUSION: This pilot study suggests that edFDG-PET may offer a less time consuming add on to standard FDG-PET/CT while being equally accurate. The results should be validated prospectively in larger trials.

Relationship between estimated glomerular filtration rate and biological half-life of 131I. Retrospective analysis in patients with differentiated thyroid carcinoma.

AIM: This retrospective study sought to investigate the relationship between biological half-life (t1/2 biol) of 131I and estimated glomerular filtration rate (eGFR) in patients with thyroid carcinoma. PATIENTS, METHODS: 96 patients with differentiated thyroid carcinoma (69 women, 27 men, mean age 64.0 ± 13.6 years) and diagnostic and therapeutic administration of 131I were considered. Patients with pronounced specific iodine storage were not included in the study. The eGFR was estimated according to the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula, the t1/2 biol via dosimetry. Patients were subdivided in groups with normal clearance (NC) (n = 37, 38.5%), medium clearance (MC) (n = 48, 50.0%), and low clearance (LC) (n = 11, 11.5%) (eGFR ≥ 90; 60-89; 15-59 ml/min per 1.73 m2, respectively). The relationship between eGFR and t1/2 biol of 131I was modeled using a power function. RESULTS: The groups significantly differed in terms of age (NC 53.8, MC 68.6, and 78.0 years, respectively), serum creatinine levels (NC: 0.71; MC: 0.85; LC: 1.18 mg/dl), and t1/2 biol (NC: 0.53; MC: 0.71; LC: 1.01 days). The t1/2 biol was significantly influenced only by eGFR, and not by age, gender, or body weight. The relationship between t1/2 biol of 131I and eGFR was described by the formula t1/2 biol = 20.3 · eGFR-0.782. CONCLUSIONS: The calculated relationship between renal function and t1/2 biol of 131I can be used in principle to estimate a dose reduction for patients with renal insufficiency. The model, however, gives erroneous results in individual cases and therefore a routine utilization cannot be recommended. Prospective studies are necessary, based on larger patient numbers and more accurate methods for dose rate measurement and GFR.

Circulating epithelial cells in patients with thyroid carcinoma. Can they be identified in the blood?

GOAL: To investigate whether circulating epithelial cells (CEC) recognized via the epithelial cell adhesion molecule (EpCAM) can be identified in the blood of patients with thyroid carcinoma, given that CEC have already been detected in other types of carcinoma and are considered a potential marker of tumour dissemination. PATIENTS, METHODS: Blood samples of patients with active differentiated thyroid carcinoma (DTC) (n = 50) were compared to samples of patients with: a) recent surgical excision of a thyroid carcinoma (postOP-DTC) (n = 16); b) athyreotic, tumour-free status after radioiodine ablation (AT-DTC) (n= 33); and c) benign thyroid diseases (BTD) (n = 51). Samples of volunteers with normal thyroid parameters (NT) (n = 12) were also investigated. Cells from EDTA-blood were subjected to erythrocyte lysis, isolated by centrifugation, and incubated with a fluorescence-labeled antibody against EpCAM. The numbers of vital cells were counted via fluorescence microscopy. RESULTS: CEC were identified in all groups, with the postOP-DTC group showing the highest mean CEC numbers of all groups. The DTC group had significantly higher CEC numbers than the NT group, and numerically higher numbers than the other groups, although not reaching statistical significance. Within the DTC group there was a correlation between levels of serum thyroglobulin and numbers of CEC (r = 0.409, p = 0.003). CONCLUSIONS: High CEC numbers were not specific to thyroid carcinoma. The methodology used here, based on a single measurement does not allow to identify severe forms of DTC, emphasizing the need of longitudinal measurements throughout therapy. Detection and characterization of tumour thyroid cells in circulation should be based on additional consideration of tissue-specific characteristics.