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.

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.

Dynamic behaviour of selected PET tracers in embryonated chicken eggs

La tomografía por emisión de positrones/tomografía computarizada (PET/TC) es una técnica establecida en la investigación preclínica de enfermedades en modelos de animales peque˜nos y en el diagnóstico clínico de cáncer. Esta técnica combina la información funcional del biomarcador emisor de positrones con los datos anatómicos de la imagen TC, permitiendo de este modo la investigación in vivo de los procesos biológicos en 4 dimensiones. Recientemente, el crecimiento de los huesos de los embriones de pollo se ha podido monitorizar usando PET/TC con 18F fluoruro como trazador óseo. Estamos interesados en la investigación de otros trazadores PET/TC en embriones de pollo como sistema de modelo in vivo. Para ello, evaluamos varios radiotrazadores usados habitualmente en pruebas clínicas o sintetizamos aquellos que no estaban disponibles comercialmente. Utilizando un microPET/TC de animales peque˜nos, evaluamos las características de 18F, 68Ga y 64Cu cloruro en huevos con sondaje. La 2-Deoxy-2[18F]fluorodeoxiglucosa (18F FDG) estaba absorbida en los sitios de crecimiento de los huesos. El 64Cu cloruro y un anticuerpo de unión a fibrillas de amiloide marcado con 68Ga se acumularon en el hígado, mientras que el 68Ga ligado a un conjugado de desferroxamina disminuyó con el tiempo en ese mismo órgano. Los resultados indican que estos biomarcadores pueden ser utilizados para la monitorización de procesos biológicos en huevos de pollo como modelo animal (AU)

Positron emission tomography/computer tomography (PET/CT) is an established method in preclinical research in small animal disease models and the clinical diagnosis of cancer. It combines functional information of the positron-emitting biomarker with the anatomical data obtained from the CT image. Thus, it allows for 4D in vivo investigation of biological processes. Recently, PET/CT was used to monitor bone growth of chicken embryos using 18F-fluoride as a bone-seeking tracer. We are interested in investigating the adequacy of additional PET/CT tracers in chicken embryos as an in vivo model system. For this reason, we evaluated several positron emitting compounds typically used in clinical tests or if these were not commercially available, we synthesised them. We studied the properties of these 18F- and 68Ga-labelled tracers and of 64Cu-chloride in catheterised eggs via small animal microPET/CT. 2-Deoxy-2-[18F]fluoroglucose ([18F]FDG) was primarily absorbed at the sites of bone growth. 64Cu chloride and a 68Ga-labelled amyloid-fibril-binding antibody accumulated in the liver, while the 68Ga-albumin desferrioxamine conjugate signal in liver decreased over time. These results indicate that these biomarkers can potentially be used for the monitoring of biological processes in chicken eggs as an animal model (AU)

Dynamic behaviour of selected PET tracers in embryonated chicken eggs.

Positron emission tomography/computer tomography (PET/CT) is an established method in preclinical research in small animal disease models and the clinical diagnosis of cancer. It combines functional information of the positron-emitting biomarker with the anatomical data obtained from the CT image. Thus, it allows for 4D in vivo investigation of biological processes. Recently, PET/CT was used to monitor bone growth of chicken embryos using (18)F-fluoride as a bone-seeking tracer. We are interested in investigating the adequacy of additional PET/CT tracers in chicken embryos as an in vivo model system. For this reason, we evaluated several positron emitting compounds typically used in clinical tests or if these were not commercially available, we synthesised them. We studied the properties of these (18)F- and (68)Ga-labelled tracers and of (64)Cu-chloride in catheterised eggs via small animal microPET/CT. 2-Deoxy-2-[(18)F]fluoroglucose ([(18)F]FDG) was primarily absorbed at the sites of bone growth. (64)Cu chloride and a (68)Ga-labelled amyloid-fibril-binding antibody accumulated in the liver, while the (68)Ga-albumin desferrioxamine conjugate signal in liver decreased over time. These results indicate that these biomarkers can potentially be used for the monitoring of biological processes in chicken eggs as an animal model.

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.

3D ultrasound DICOM data of the thyroid gland. First experiences in exporting, archiving, second reading and 3D processing.

PURPOSE: It has recently become possible to generate and archive three-dimensional ultrasound (3D-US) volume data with the DICOM standard Enhanced Ultrasound Volume Storage (EUVS). The objective of this study was to examine the application of the EUVS standard based on the example of thyroid ultrasound. PATIENTS, METHODS: 32 patients, who were referred for thyroid diagnosis, were given a 3D-US examination of the thyroid gland (GE Voluson E8, convex 3D probe RAB4-8-D). The 3D data sets were exported to EUVS. Necessary additions to DICOM entries and transformation into an established DICOM standard were carried out. The visual assessment and volume measurements were performed by two experts on nuclear medicine using standard software in our hospital. RESULTS: In 24/32 (75%) of the patients, the whole organ was successfully recorded in a single 3D scan; in 8/32 (25%), only part of organ could be covered. In all cases, 3D-US data could be exported and archived. After supplementing the DICOM entry Patient Orientation and transformation into the DICOM PET format, 3D-US data could be displayed in the correct orientation and size at any viewing workstation and any web browser-based PACS viewer. Afterwards, 3D processing such as multiplanar reformation, volumetric measurements and image fusion with data of other cross sectional modalities could be performed. The intraclass correlation of the volume measurements was 0,94 and the interobserver variability was 5.7%. CONCLUSION: EUVS allows the generation, distribution and archiving of 3D-US data of the thyroid, facilitates a second reading by another physician and creates conditions for advanced 3D processing using routine software.

Treatment with granulocyte-colony stimulating factor in patients with acute myocardial infarction. Evidence for a stimulation of neovascularization and improvement of myocardial perfusion.

BACKGROUND: Stem cell therapy has been suggested to be beneficial in patients after acute myocardial infarction (AMI). Strategies of treatment are either a local application of mononuclear bone marrow cells (BMCs) into the infarct-related artery or a systemic therapy with the granulocyte-stimulating factor (G-CSF) to mobilize BMCs. Nevertheless, the mechanisms responsible for improvement of cardiac function and perfusion are speculative at present. This study has been performed to investigate the effect of G-CSF on systemic levels of vascular growth factors and chemokines responsible for neovascularization, that might help to understand the positive effects of a G-CSF therapy after AMI. METHODS AND RESULTS: Five patients in the treatment group and 5 patients in the control group were enrolled in this study. The patients in the treatment group received 10 microg/kg bodyweight/day of G-CSF subcutaneously for a mean treatment duration of 6.6 +/- 1.1 days. In both groups, levels of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and monocyte chemotactic protein-1 (MCP-1) were measured on day 2 to 3 and day 5 after AMI. The regional wall perfusion and the ejection fraction (EF) were evaluated before discharge and after 3 months with ECG-gated MIBI-SPECT and radionuclide ventriculography, respectively. Significant higher levels of VEGF (p < 0.01), bFGF (p < 0.05) and MCP-1 (p < 0.05) were found in the treatment group compared to the control group. Levels of VEGF and bFGF remained on a plateau during the G-CSF treatment and decreased significantly in the control group. The wall perfusion improved significantly within the treatment group and between the groups (p < 0.05), respectively. The EF improved significantly within the treatment group (p < 0.05), but the change of the EF between the groups was not significant. CONCLUSION: In patients with AMI, the treatment with G-CSF modulates the formation of vascular growth factors that might improve neovascularization and result in an improved myocardial perfusion and function.

[Mobilization of stem cells by granulocyte colony-stimulating factor for the regeneration of myocardial tissue after myocardial infarction]. / Mobilisation von Stammzellen durch den Granulozyten-Kolonie stimulierenden Faktor zur Regeneration myokardialen Gewebes nach Herzinfarkt.

BACKGROUND AND OBJECTIVE: Animal data suggest that mobilized bone marrow cells (BMC) may contribute to tissue regeneration after myocardial infarction (MI). However the safety, feasibility and efficacy of treatment with granulocyte colony-stimulating factor (G-CSF) to mobilize BMC after acute myocardial infarction in patients is unknown. We analysed cardiac function and perfusion in 5 patients who were treated with G-CSF in addition to standard therapeutical regimen. METHODS AND RESULTS: 48 h after successful recanalization and stent implantation in 5 patients with acute MI, the patients received 10 micro g/kg bodyweight/day G-CSF subcutaneously for a mean treatment duration of 7.6+/-0.5 days. Peak value of CD34 (+) cells, a multipotent subfraction of bone marrow cells, was reached after 5.0+/-0.7 days. After 3 months of follow-up global left ventricular ejection fraction (determined by radionuclid-ventriculography) increased significantly from 42.2+/-6.6 % to 51.6+/-8.3 % (P<0.05). The wall motion score and the wall perfusion score (determined by ECG gated SPECT) decreased from 13.5+/-3.6 to 9.9+/-3.5 (P<0.05) and from 9.6+/-2.9 to 7.0+/-4.5 (P<0.05), respectively, indicating a significant improvement of myocardial function and perfusion. No severe side effects of G-CSF treatment could be observed. Malignant arrhythmias were not observed either. CONCLUSION: In patients with acute MI, treatment with G-CSF to mobilize BMC appears to be well tolerable under clinical conditions. Improved cardiac function and perfusion may be attributed to BMC-associated promotion of myocardial regeneration and neovascularization.

[The value of fluorodeoxyglucose positron emission tomography (FDG-PET) in differentiation of pancreatic lesions]. / Die Wertigkeit der Fluordeoxyglukose Positronenemissionstomographie (FDG-PET) in der Diagnostik von Pankreasprozessen.

Fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) is a functional imaging modality that is based on the metabolic activity which is higher in most malignant tumors than benign tissues. This short review describes the basics of FDG-PET and gives a discussion of its role in differentiation of focal pancreatic lesions. The diagnostic accuracy in patients with active inflammation or cancer of the pancreas can be improved by dynamic acquisition of focal pancreatic lesions.

Serial positron emission tomographic findings in an atypical presentation of fatal familial insomnia.

BACKGROUND: Genetic analyses of fatal familial insomnia, a prion disease, disclose a broader range of symptoms than previously described. Although insomnia and dysautonomia have been described as hallmarks of the disease, there is substantial variability in clinical presentation. OBJECTIVE: To evaluate serial fluorodeoxyglucose positron emission tomographic and electroencephalographic findings in atypical fatal familial insomnia without clinical insomnia. PATIENT: A 63-year-old man who had a history of gait ataxia developed rapidly progressive dementia with mild dysautonomic features. Genetic investigation confirmed diagnosis of fatal familial insomnia (D178N mutation of the prion protein gene and Val/Met polymorphism on position 129 of the mutated allele) with typical neuropathologic findings. RESULTS: Clinical signs were not specific. An electroencephalogram showed scanty triphasiclike elements and general slowing. We found thalamic hypometabolism in positron emission tomographic scans to be present in a very early stage with progressive deterioration, and patchy cortical alterations showing progression over 6 months. CONCLUSIONS: In the absence of clear clinical signs, an electroencephalogram was of major diagnostic value, although its specificity in fatal familial insomnia is under debate. Selective thalamic hypometabolism seems to be an early marker in fatal familial insomnia, while cortical changes vary with clinical presentation and stage.