18F-PSMA-1007 PET/CT for response assessment in patients with metastatic renal cell carcinoma undergoing tyrosine kinase or checkpoint inhibitor therapy: preliminary results.

INTRODUCTION: Tyrosine kinase (TKI) and checkpoint inhibitors (CI) prolonged overall survival in metastatic renal cell carcinoma (mRCC). Early prediction of treatment response is highly desirable for the individualization of patient management and improvement of therapeutic outcome; however, serum biochemistry is unable to predict therapeutic efficacy. Therefore, we compared 18F-PSMA-1007 PET imaging for response assessment in mRCC patients undergoing TKI or CI therapy compared to CT-based response assessment as the current imaging reference standard. METHODS: 18F-PSMA-1007 PET/CT was performed in mRCC patients prior to initiation of systemic treatment and 8 weeks after therapy initiation. Treatment response was evaluated separately on 18F-PSMA-PET and CT. Changes on PSMA-PET (SUVmean) were assessed on a per patient basis using a modified PERCIST scoring system. Complete response (CRPET) was defined as absence of any uptake in all target lesions on posttreatment PET. Partial response (PRPET) was defined as decrease in summed SUVmean of > 30%. The appearance of new, PET-positive lesions or an increase in summed SUVmean of > 30% was defined as progressive disease (PDPET). A change in summed SUVmean of ± 30% defined stable disease (SDPET). RECIST 1.1 criteria were used for response assessment on CT. Results of radiographic response assessment on PSMA-PET and CT were compared. RESULTS: Overall, 11 mRCC patients undergoing systemic treatment were included. At baseline PSMA-PET1, all mRCC patients showed at least one PSMA-avid lesion. On follow-up PET2, 3 patients showed CRPET, 3 PRPET, 4 SDPET, and 1 PDPET. According to RECIST 1.1, 1 patient showed PRCT, 9 SDCT, and 1 PDCT. Overall, concordant classifications were found in only 2 cases (2 SDCT + PET). Patients with CRPET on PET were classified as 3 SDCT on CT using RECIST 1.1. By contrast, the patient classified as PRCT on CT showed PSMA uptake without major changes during therapy (SDPET). However, among 9 patients with SDCT on CT, 3 were classified as CRPET, 3 as PRPET, 1 as PDPET, and only 2 as SDPET on PSMA-PET. CONCLUSION: On PSMA-PET, heterogeneous courses were observed during systemic treatment in mRCC patients with highly diverging results compared to RECIST 1.1. In the light of missing biomarkers for early response assessment, PSMA-PET might allow more precise response assessment to systemic treatment, especially in patients classified as SD on CT.

Biodistribution and first clinical results of 18F-SiFAlin-TATE PET: a novel 18F-labeled somatostatin analog for imaging of neuroendocrine tumors.

INTRODUCTION: PET/CT using 68Ga-labeled somatostatin analogs (SSA) targeting somatostatin receptors (SSR) on the cell surface of well-differentiated neuroendocrine tumors (NET) represents the clinical reference standard for imaging. However, economic and logistic challenges of the 68Ge/68Ga generator-based approach have disadvantages over 18F-labeled compounds. Here, we present the first in-human data of 18F-SiFAlin-TATE, a novel 18F-labeled, SSR-targeting peptide. The aim was to compare the intra-individual biodistribution, tumor uptake, and image quality of 18F-SiFAlin-TATE to the clinical reference standard 68Ga-DOTA-TOC. METHODS: Thirteen patients with NET staged with both 68Ga-DOTA-TOC and 18F-SiFAlin-TATE PET/CT have been included in this retrospective analysis. We compared the biodistribution in normal organs and tumor uptake of NET lesions by SUVmean and SUVmax measurement for tracers. Additionally mean and max tumor-to-liver (TLR) and tumor-to-spleen ratios (TSR) have been calculated by division of SUVmean and SUVmax of tumor lesions by the SUVmean of the liver and spleen, respectively. Additionally, image quality was visually rated by 5 blinded readers and an intra-class correlation (ICC) analysis on inter-observer agreement has been performed. RESULTS: Compared with 68Ga-DOTA-TOC, the biodistribution of 18F-SiFAlin-TATE showed somewhat higher, however, statistically not significant higher uptake in the liver, spleen, and adrenal glands. Significantly higher uptake was observed in the kidneys. Tumor uptake was higher in most tumor lesions with significantly higher uptake in common metastatic sites of NET including the liver (SUVmax 18.8 ± 8.4 vs. 12.8 ± 5.6; p < 0.001), lymph nodes (SUVmax 23.8 ± 20.7 vs. 17.4 ± 16.1; p < 0.001) and bone (SUVmax 16.0 ± 10.1 vs. 10.3 ± 5.7; p < 0.01) for 18F-SiFAlin-TATE. The high tumor uptake resulted in favorable TLR and TSR, comparable with that of 68Ga-DOTA-TOC. The ICC analysis on the inter-observer agreement on image quality was substantial and almost perfect. Image quality was rated as excellent in most cases in both 68Ga-DOTA-TOC and 18F-SiFAlin-TATE PET. CONCLUSION: The favorable characteristics of 18F-SiFAlin-TATE with a high image quality, the kit-like labeling procedure, and the promising clinical performance enable improved logistics and diagnostic possibilities for PET imaging of NET. Our first clinical results warrant further systematic studies investigating the clinical use of 18F-SiFAlin-TATE in NET patients.

[Neuroendocrine tumors of the stomach, duodenum and pancreas : Value of (hybrid) radiological diagnostics]. / Neuroendokrine Tumoren von Magen, Duodenum und Pankreas : Stellenwert der (hybriden) radiologischen Diagnostik.

CLINICAL/METHODICAL ISSUE: Neuroendocrine tumors (NET) of the stomach, duodenum and pancreas are rare tumors with a low incidence but the exact tumor localization and staging diagnostics are of critical importance for further planning of treatment. STANDARD RADIOLOGICAL METHODS: Standard primary diagnostic methods include multimodal imaging with computed tomography (CT) and magnetic resonance imaging (MRI) but in 20-50% of the cases the localization of the primary tumor cannot be identified. METHODICAL INNOVATIONS: Modern hybrid imaging procedures combine radiological procedures and functional imaging, e.g. using somatostatin receptor (SSR) positron emission tomography CT (PET)/CT imaging. For the exact diagnostics of the primary tumor and distant metastases morphological and functional aspects can be combined for targeted diagnostics. For primary tumor staging a sensitivity of 80.0% and a specificity of 88.4% are given in the literature. PERFORMANCE: The application of SSR PET/CT led to a change in patient management in 44% of all cases according to a recently published meta-analysis and therefore had a significant influence on the further procedure. ASSESSMENT: The use of SSR PET/CT can provide critical information for further treatment and can lead to a significant change in treatment management in a relevant proportion of patients. PRACTICAL RECOMMENDATIONS: Radiological imaging diagnostics and in particular hybrid functional imaging procedures using PET/CT will become increasingly more relevant for the diagnostics, treatment and follow-up of NET patients.

[Pulmonary carcinoids and carcinoids of the small intestine]. / Karzinoide der Lunge und im Abdomen.

CLINICAL/METHODICAL ISSUE: Pulmonary carcinoids and carcinoids of the small intestine (jejunum and ileum) are often asymptomatic and can affect various parts of the body, which makes diagnosis difficult. STANDARD RADIOLOGICAL METHODS: Contrast-enhanced computed tomography (CE-CT) is commonly used for primary diagnostics. In case of concomitant pulmonary consolidation (e.g., atelectasis or pneumonia), tumor lesions can be obscured. In addition, differentiation between atypical (AC) and typical carcinoids (TC) is not possible using CT. Small tumors of the small intestine are easily overlooked (sensitivity: 50-85%, specificity: 25-97%, based on the literature). Additional functional imaging evaluation using hybrid imaging techniques can be applied, e.g., positron emission tomography/computed tomography (PET/CT). METHODICAL INNOVATIONS/PERFORMANCE: Depending on the histological characteristics of the tumor, PET/CT scans can be performed with different tracers. Since most carcinoids (e.g., TC) express somatostatin receptors (SSR), 68 gallium-radiolabeled PET tracers (e.g. 68 Ga-DOTA-TOC) are commonly used (sensitivity: 88-93%, specificity: 88-95%, based on the literature). Poorly differentiated carcinoids (e.g., AC) demonstrate lower SSR expression; thus, use of 18F­FDG (sensitivity: 37-72%, based on the literature) is indicated. In principle, these methods enable a noninvasive prognostic differentiation based on SSR expression and 18F­FDG uptake. However, the diagnosis must always be histologically confirmed. ACHIEVEMENTS/PRACTICAL RECOMMENDATIONS: Hybrid imaging with CE-CT and PET is useful to detect pulmonary carcinoids and carcinoids of the small intestine, respectively, and can be utilized for primary diagnostics and restaging.

[Pheochromocytoma and paraganglioma : Importance of diagnostic imaging]. / Phäochromozytom und Paragangliom : Stellenwert der bildgebenden Diagnostik.

CLINICAL BACKGROUND: If pheochromocytoma (PC) or paraganglioma (PGL) is diagnosed based on serologic studies, imaging is required to locate the adrenal mass for further management. Besides pathognomonic hormonal findings, PC/PGL can exhibit typical imaging features. However, PC/PGL can also show morphological overlap with other pathologies. STANDARD RADIOLOGICAL METHODS: The modality of choice for evaluation of PC is CT. In case of extra-adrenal location, MRI is superior to CT. Imaging with PET-CT provides complementary information in the differentiation of PC/PGL and is recommended as the imaging modality of choice for malignant PC/PGL. 68Ga-DOTATATE (or 68Ga-DOTATOC/ 68Ga-DOTANOC) PET-CT has high sensitivity for SDHx-mutated PC/PGL and serves for planning of radioreceptor therapy with somatostatin analogues. In contrast, 123I-metaiodobenzylguanidine (MIBG) scintigraphy is important in assessing the potential efficacy of radioreceptor therapy with MIBG. METHODICAL DETAILS: The CT protocol for PC evaluation should include non-enhanced, arterial, portal-venous and late phases; the latter for the evaluation of wash-out. Recent studies indicate non-enhanced CT alone may be sufficient to rule out PC. For MRI, in- and opposed-phase sequences should be additionally acquired. PRACTICAL RECOMMENDATIONS: A relevant proportion of PC is diagnosed incidentally. Therefore, imaging of PC will gain further importance. Recent studies show better response rates of PC/PGL after radioreceptor therapy with somatostatin analogues (177Lu-DOTATATE) than with MIBG. Therefore, 68Ga-DOTATATE PET-CT gains further importance-for diagnostic imaging and therapy planning.

[Radiological diagnostics in CUP syndrome]. / Radiologische Diagnostik des CUP-Syndroms.

CLINICAL/METHODICAL ISSUE: Imaging plays an essential role in the therapeutic management of cancer of unknown primary (CUP) patients for localizing the primary tumor, for the identification of tumor entities for which a dedicated therapy regimen is available and for the characterization of clinicopathological subentities that direct the subsequent diagnostic and therapeutic strategy. STANDARD RADIOLOGICAL METHODS: Modalities include conventional x-ray, computed tomography (CT), magnetic resonance imaging (MRI) and ultrasound as well as positron emission tomography (PET)-CT and MRI-PET. PERFORMANCE: In whole body imaging CT has a high sensitivity for tumor entities which frequently present as a metastasized cancer illness. According to the current literature CT is diagnostic in 86% of patients with pancreatic carcinoma, in 36% of patients with colon carcinoma and in 74% of patients with lung carcinoma. Additionally a meta-analysis showed that for patients with squamous cell carcinoma and cervical lymph node metastases a positive diagnosis was possible in 22% of the cases using CT, in 36% using MRI and in 28-57% using 18F-fluorodeoxyglucose PET-CT ((18)F-FDG PET-CT). In addition, MRI plays an important role in the localization of primary occult tumors (e.g. breast and prostate) because of its high soft tissue contrast and options for functional imaging. ACHIEVEMENTS: At the beginning of the diagnostic algorithm stands the search for a possible primary tumor and CT of the neck, thorax and abdomen is most frequently used for whole body staging. Subsequent organ-specific imaging examinations follow, e.g. mammography in women with axillary lymphadenopathy. For histological and immunohistochemical characterization of tumor tissue, imaging is also applied to identify the most accessible and representative tumor manifestation for biopsy. Tumor biopsy may be guided by CT, MRI or ultrasound and MRI also plays a central role in the localization of primary occult tumors because of superior soft tissue contrast and options for functional imaging (perfusion, diffusion), e.g. investigation of breast carcinoma or prostate carcinoma. PRACTICAL RECOMMENDATIONS: Whole body staging stands at the beginning of the diagnostic algorithm in CUP syndrome to localize a potential primary tumor. Clinically, contrast-enhanced CT of the neck, thorax and abdomen is frequently applied; however, many studies have demonstrated augmented sensitivity of (18)F-FDG PET-CT for the detection of primary tumors and metastatic tumor manifestations.

[Imaging of neuroendocrine tumors of the gastrointestinal tract : Value of (hybrid) imaging diagnostics in radiology]. / Bildgebung von neuroendokrinen Tumoren des Gastrointestinaltrakts : Bedeutung der (hybriden) bildgebenden Diagnostik in der Radiologie.

CLINICAL/METHODICAL ISSUE: Neuroendocrine tumors (NET) represent a heterogeneous group of rare tumors that predominantly arise in the gastrointestinal tract. At the time of initial diagnosis, the NET has already spread locoregionally in about half of the patients, and 27% of patients have already developed distant metastases. Since this plays a crucial role in therapy planning, accurate diagnostic imaging is important. STANDARD RADIOLOGICAL METHODS: Due to its high temporal and spatial resolution (multiphasic including arterial phase), computed tomography (CT) plays a decisive role in primary staging and follow-up care, while magnetic resonance imaging (MRI) with its excellent soft tissue contrast offers advantages in the assessment of parenchymal organs in the upper abdomen. METHODICAL INNOVATIONS: Somatostatin receptor (SSR) positron emission tomography (PET) provides additional functional information that not only helps to detect the primary tumor and distant metastases, but also has a significant influence on therapeutic management in a theranostic approach. PERFORMANCE: Hybrid imaging using SSR-PET/CT has proven to be particularly effective in the detection of NET. Compared to conventional imaging, it provides additional information in 68% of patients, which has a significant impact on clinical management. ACHIEVEMENTS: Imaging of NET requires the combined use of various methods such as ultrasound, CT, MRI, and PET/CT to enable accurate diagnosis and effective treatment planning. PRACTICAL RECOMMENDATIONS: SSR-PET/CT is a valuable tool for the accurate staging of neuroendocrine tumors of the gastrointestinal tract, especially with small metastases, while MRI with hepatocyte-specific contrast agent and diffusion-weighted imaging is useful for the specific assessment of liver metastases.

Diagnostic accuracy of SSR-PET/CT compared to histopathology in the identification of liver metastases from well-differentiated neuroendocrine tumors.

BACKGROUND: Histopathology is the reference standard for diagnosing liver metastases of neuroendocrine tumors (NETs). Somatostatin receptor-positron emission tomography / computed tomography (SSR-PET/CT) has emerged as a promising non-invasive imaging modality for staging NETs. We aimed to assess the diagnostic accuracy of SSR-PET/CT in the identification of liver metastases in patients with proven NETs compared to histopathology. METHODS: Histopathologic reports of 139 resected or biopsied liver lesions of patients with known NET were correlated with matching SSR-PET/CTs and the positive/negative predictive value (PPV/NPV), sensitivity, specificity, and diagnostic accuracy of SSR-PET/CT were evaluated. PET/CT reading was performed by one expert reader blinded to histopathology and clinical data. RESULTS: 133 of 139 (95.7%) liver lesions showed malignant SSR-uptake in PET/CT while initial histopathology reported on 'liver metastases of NET´ in 127 (91.4%) cases, giving a PPV of 91.0%. Re-biopsy of the initially histopathologically negative lesions (reference standard) nevertheless diagnosed 'liver metastases of NET' in 6 cases, improving the PPV of PET/CT to 95.5%. Reasons for initial false-negative histopathology were inadequate sampling in the sense of non-target biopsies. The 6 (4.3%) SSR-negative lesions were all G2 NETs with a Ki-67 between 2-15%. CONCLUSION: SSR-PET/CT is a highly accurate imaging modality for the diagnosis of liver metastases in patients with proven NETs. However, we found that due to the well-known tumor heterogeneity of NETs, specifically in G2 NETs approximately 4-5% are SSR-negative and may require additional imaging with [18F]FDG PET/CT.

[Preclinical imaging in animal models of radiation therapy]. / Präklinische Bildgebung im Tiermodell bei Strahlentherapie.

CLINICAL/METHODICAL ISSUE: Modern radiotherapy benefits from precise and targeted diagnostic and pretherapeutic imaging. STANDARD RADIOLOGICAL METHODS: Standard imaging modalities, such as computed tomography (CT) offer high morphological detail but only limited functional information on tumors. METHODICAL INNOVATIONS: Novel functional and molecular imaging modalities provide biological information about tumors in addition to detailed morphological information. PERFORMANCE: Perfusion magnetic resonance imaging (MRI) CT or ultrasound-based perfusion imaging as well as hybrid modalities, such as positron emission tomography (PET) CT or MRI-PET have the potential to identify and precisely delineate viable and/or perfused tumor areas, enabling optimization of targeted radiotherapy. Functional information on tissue microcirculation and/or glucose metabolism allow a more precise definition and treatment of tumors while reducing the radiation dose and sparing the surrounding healthy tissue. ACHIEVEMENTS: In the development of new imaging methods for planning individualized radiotherapy, preclinical imaging and research plays a pivotal role, as the value of multimodality imaging can only be assessed, tested and adequately developed in a preclinical setting, i.e. in animal tumor models. PRACTICAL RECOMMENDATIONS: New functional imaging modalities will play an increasing role for the surveillance of early treatment response during radiation therapy and in the assessment of the potential value of new combination therapies (e.g. combining anti-angiogenic drugs with radiotherapy).

[Contrast-enhanced ultrasound in animal models]. / Kontrastverstärkter Ultraschall der Skelettmuskulatur.

In the past the detection of tumor perfusion was achieved solely via invasive procedures, such as intravital microscopy or with the help of costly modalities, such as multidetector computed tomography (MDCT), magnetic resonance tomography (MRT) or the combined use of positron emission tomography and computed tomography (PET/CT). Ultrasound offers the non-invasive display of organs without usage of ionizing radiation and it is widely available. However, colour-coded ultrasound and power Doppler do not allow the detection of tumor microcirculation. The introduction of contrast-enhanced ultrasound (CEUS) as well as new high-frequency ultrasound probes made it possible to detect and quantify tumor microcirculation with high resolution. CEUS has been used clinically on human beings for more than 10 years. During the last years different tumor models in experimental animals were used for the establishment of this new technique, e.g. in rats, hamsters and mice. CEUS allows the detection of functional parameters, such as the angiogenetic metabolic status of tissue pretreatment and posttreatment. Further research is required to solve the problems of absolute quantification of these perfusion parameters to allow the comparison of CEUS with other modalities (e.g. MRT and CT).

[New aspects of MRI for diagnostics of large vessel vasculitis and primary angiitis of the central nervous system]. / Neue Aspekte der MRT-Bildgebung zur Diagnostik der Großgefäßvaskulitiden sowie der primären Angiitis des zentralen Nervensystems.

Vasculitis is a rare disease and clinical symptoms are often unspecific. Accurate and early diagnosis is mandatory in order to prevent complications, such as loss of vision or stroke. Imaging techniques can contribute to establishing a definite diagnosis and to evaluate disease activity and the extent of the disease in various vascular regions. Conventional imaging methods, such as computed tomography (CT) and magnetic resonance (MR) angiography, as well as digital subtraction angiography allow the vessel lumen but not the vessel wall to be depicted. However, vasculitis is a disease which primarily affects the vessel wall, therefore conventional imaging modalities often fail to make a definite diagnosis. Recently black-blood high resolution MR in vivo imaging has been used to visualize cervical and intracranial vasculitis. This review article presents imaging protocols for intracranial and cervical black-blood MR imaging and clinical cases with large vessel vasculitis and vasculitis of the central nervous system. Furthermore the current literature, examples of the most common differential diagnoses of cervical and cranial arteriopathy and the potential of other imaging modalities, such as PET/CT and ultrasound will be discussed.

Advanced Molecular Imaging in Histologically Verified Metanephric Adenoma.

Metanephric adenoma (MA) describes a rare renal tumor and is generally considered a benign lesion. However, there are cases with regional lymphogenic and distant metastases. Noninvasive diagnosis of MA using conventional imaging remains challenging. Here, we describe a case of histologically verified MA with additional advanced molecular imaging consisting of 18F-PSMA-1007 PET/CT, 99mTc-Sestamibi SPECT and contrast-enhanced ultrasound.

Alternate vehicles for diagnostic patch testing: an update.

AIM: The aim of the present study was to review the literature subsequent to 2001 for recent information on alternate vehicles for diagnostic patch testing. AIM: Patch testing is a standard tool in dermatoallergology used in particular in the diagnostic process of allergic contact dermatitis. While petrolatum is employed in most cases, the way vehicles can influence results may not be neglected. Alternate vehicles may clarify hitherto negative or doubtful results. METHODS: The authors searched the most important medical databases using as search terms ''contact dermatitis'', ''patch test'' and ''vehicle''. RESULTS: Data obtained by local lymph node assay and in vitro percutaneous absorption experiments suggest methods to improve penetration and immunologic response by either adding substances to petrolatum or replacing it altogether. Still, an adequate hypoirritant substitute for petrolatum remains to be discovered. In addition, one study reveals the lack of a general recommendation as to which quantity of petrolatum, and therefore dose, to apply. In the meantime, a negative or unclear patch test in a patient with allergen exposition and maybe even a history of contact dermatitis might be repeated using the scratch method, a higher allergen concentration or sodium lauryl sulphate either in the vehicle or as a control. The authors review the literature subsequent to 2001 for recent evolution of knowledge on vehicles. CONCLUSION: Little conclusive research has been done on alternate vehicles in patch testing. However, the authors recognize some interesting tendencies as to either improve the characteristics of petrolatum as a vehicle by adding substances that may heighten the immunologic response or replace it.

[Incidence and risk factors of HCV infection in a cohort of intravenous drug users in the North and East of France]. / Incidence et facteurs de risque de la séroconversion au virus de l'hépatite C dans une cohorte d'usagers de drogue intraveineux du nord-est de la France.

BACKGROUND: In order to evaluate the incidence and risk factors of infection by hepatitis C virus (HCV) among intravenous drug users we conducted a prospective cohort study of HCV and HIV negative IVDU in the North and East of France. METHODS: Two hundred and thirty-one IVDU who had injected drug at least once in their lifetime and were negative for anti-HCV and anti-HIV were followed-up every three months over a 12-month period. Serum anti-HCV and anti-HIV antibodies were tested at inclusion in the study and at the end of the follow-up. Data on injection practices and behaviours were collected at inclusion and at each visit, and a test for anti-HCV antibodies was performed on a saliva sample. When this proved positive, an ELISA test for serum anti-HCV antibodies was carried out. RESULTS: Of the 231 participants included, 165 (71.4%) underwent a final HCV and HIV serum test. The incidence was nil for HIV infection and 9% (95% CI: 4.6-13.4) person-years for HCV infection. Among IVDU who injected at least once during the last 6 months HCV infection incidence was 11% (95% CI: 4.7-17.1) person-years. The multivariate analysis carried out on the inclusion data found female sex alone to be an independent predictive factor of HCV seroconversion. In a Cox proportional hazard multivariate analysis that took into account time-dependent exposures and covariates, we found that syringe and cotton sharing were, after adjusting for other covariates, the only independent predictive factors of HCV seroconversion: hazard ratio: 6.3 [corrected] (95% CI: 1.1-35.4; [corrected] p<0.05) and 16.4 (95% CI: 1.4-190.6; [corrected] p<0.05), respectively. CONCLUSION: The transmission of the HCV virus persists among French IVDU despite an ongoing national harm reduction program. Injecting material and cotton sharing are the two major determinants of transmission in this cohort.

Evaluation of multimodality imaging using image fusion with MRI and CEUS in an experimental animal model.

PURPOSE: To evaluate the diagnostic benefits of multimodality imaging using image fusion with magnetic-resonance-imaging (MRI) and contrast-enhanced-ultrasound (CEUS) in an experimental small-animal-squamous-cell-carcinoma-model for the assessment of tissue hemodynamics and morphology. MATERIAL AND METHODS: Human hypopharynx-carcinoma-cells were injected subcutaneously into the left flank of 15 female athymic nude rats. After 10 daysof subcutaneous tumor growth, CEUS and MRI measurements were performed using a high-end-ultrasound-system and 3-T-MRI. After successful point-to-point or plan registration, the registered MR-images were simultaneously shown with the respective ultrasound sectional plane. Data evaluation was performed using the digitally stored video sequence data sets by two experienced radiologists using a subjective 5-point scale. RESULTS: CEUS and MRI are well-known techniques for the assessment of tissue hemodynamics (score: mean 3.8 ± 0.4 SD and score 3.8 ± 0.4 SD). Real-time image fusion of MRI and CEUS yielded a significant (p <  0.001) improvement in score (score 4.8 ± 0.4 SD). Reliable detection of small necrotic areas was possible in all animals with necrotic tumors. No significant intraobserver and interobserver variability was detected (kappa coefficient = +1). CONCLUSION: Image fusion of MRI and CEUS gives a significant improvement for reliable differentiation between different tumor tissue areas and simplifies investigations by showing the morphology as well as surrounding macro-/microvascularization.

Citalopram versus fluoxetine: a double-blind, controlled, multicentre, phase III trial in patients with unipolar major depression treated in general practice.

Two selective serotonin reuptake inhibitors (SSRIs), citalopram and fluoxetine, both at a daily dose of 20 mg, were compared in patients with unipolar major depression treated in general practice. This was a multicentre, double-blind, randomized trial carried out in France. The duration of treatment was 8 weeks. Patients were assessed by means of the Montgomery-Asberg Depression Rating Scale (MADRS), the 17 items Hamilton Depression Rating Scale (HAMD) and the investigator's Clinical Global Impressions (CGI), Observed and spontaneously reported adverse events were also recorded. A total of 357 patients of both sexes, aged between 21 and 73 years, entered the double-blind phase of the trial. A clear reduction of both the MADRS and the HAMD mean total scores was observed in both treatment groups with no statistically significant differences between treatments. Apart from back pain recorded more frequently in the citalopram group, no significant difference was found between the two treatment groups with regard to adverse events, and both citalopram and fluoxetine were considered to be well tolerated. It was concluded that citalopram was as effective as fluoxetine in the treatment of unipolar major depression. Citalopram showed an earlier onset of recovery than fluoxetine.

What are the reciprocal influences of randomized clinical trials and the patient-psychiatrist relationship?

The goal of this prospective investigation was to study the course and the quality of patient-psychiatrist relationships during phase II / phase III clinical trials of antidepressant medication prescribed for depressive disorders. All patients who participated in the clinical trials (and subsequently in this survey) signed written informed consent statements and were subject to random double blind treatment assignment. Retrospective analysis of 118 investigations was carried out, and the patients involved were questioned concerning their experiences and impressions during and after the study. Data show that the outcome of clinical trials of antidepressant drugs are not a function of pre-existing good patient-psychiatrist relationships. On the other hand, no effects on the patient-psychiatrist relationship were found as a result of the experimental procedure, and it can be concluded that no detrimental effects on future patient-psychiatrist relationships were incurred.

Evaluation of multimodality imaging using image fusion with ultrasound tissue elasticity imaging in an experimental animal model.

PURPOSE: To evaluate the ultrasound tissue elasticity imaging by comparison to multimodality imaging using image fusion with Magnetic Resonance Imaging (MRI) and conventional grey scale imaging with additional elasticity-ultrasound in an experimental small-animal-squamous-cell carcinoma-model for the assessment of tissue morphology. METHOD AND MATERIALS: Human hypopharynx carcinoma cells were subcutaneously injected into the left flank of 12 female athymic nude rats. After 10 days (SD ± 2) of subcutaneous tumor growth, sonographic grey scale including elasticity imaging and MRI measurements were performed using a high-end ultrasound system and a 3T MR. For image fusion the contrast-enhanced MRI DICOM data set was uploaded in the ultrasonic device which has a magnetic field generator, a linear array transducer (6-15 MHz) and a dedicated software package (GE Logic E9), that can detect transducers by means of a positioning system. Conventional grey scale and elasticity imaging were integrated in the image fusion examination. After successful registration and image fusion the registered MR-images were simultaneously shown with the respective ultrasound sectional plane. Data evaluation was performed using the digitally stored video sequence data sets by two experienced radiologist using a modified Tsukuba Elasticity score. The colors "red and green" are assigned for an area of soft tissue, "blue" indicates hard tissue. RESULTS: In all cases a successful image fusion and plan registration with MRI and ultrasound imaging including grey scale and elasticity imaging was possible. The mean tumor volume based on caliper measurements in 3 dimensions was ~323 mm3. 4/12 rats were evaluated with Score I, 5/12 rates were evaluated with Score II, 3/12 rates were evaluated with Score III. There was a close correlation in the fused MRI with existing small necrosis in the tumor. None of the scored II or III lesions was visible by conventional grey scale. CONCLUSION: The comparison of ultrasound tissue elasticity imaging enables a secure differentiation between different tumor tissue areas in comparison to image fusion with MRI in our small study group. Therefore ultrasound tissue elasticity imaging might be used for fast detection of tumor response in the future whereas conventional grey scale imaging alone could not provide the additional information. By using standard, contrast-enhanced MRI images for reliable and reproducible slice positioning, the strongly user-dependent limitation of ultrasound tissue elasticity imaging may be overcome, especially for a comparison between baseline and follow-up measurements.

Microbubbles as a scattering contrast agent for grating-based x-ray dark-field imaging.

In clinically established-absorption-based-biomedical x-ray imaging, contrast agents with high atomic numbers (e.g. iodine) are commonly used for contrast enhancement. The development of novel x-ray contrast modalities such as phase contrast and dark-field contrast opens up the possible use of alternative contrast media in x-ray imaging. We investigate using ultrasound contrast agents, which unlike iodine-based contrast agents can also be administered to patients with renal impairment and thyroid dysfunction, for application with a recently developed novel x-ray dark-field imaging modality. To produce contrast from these microbubble-based contrast agents, our method exploits ultra-small-angle coherent x-ray scattering. Such scattering dark-field x-ray images can be obtained with a grating-based x-ray imaging setup, together with refraction-based differential phase-contrast and the conventional attenuation contrast images. In this work we specifically show that ultrasound contrast agents based on microbubbles can be used to produce strongly enhanced dark-field contrast, with superior contrast-to-noise ratio compared to the attenuation signal. We also demonstrate that this method works well with an x-ray tube-based setup and that the relative contrast gain even increases when the pixel size is increased from tenths of microns to clinically compatible detector resolutions about up to a millimetre.