PET/CT imaging of c-Myc transgenic mice identifies the genotoxic N-nitroso-diethylamine as carcinogen in a short-term cancer bioassay.

BACKGROUND: More than 100,000 chemicals are in use but have not been tested for their safety. To overcome limitations in the cancer bioassay several alternative testing strategies are explored. The inability to monitor non-invasively onset and progression of disease limits, however, the value of current testing strategies. Here, we report the application of in vivo imaging to a c-Myc transgenic mouse model of liver cancer for the development of a short-term cancer bioassay. METHODOLOGY/PRINCIPAL FINDINGS: µCT and ¹8F-FDG µPET were used to detect and quantify tumor lesions after treatment with the genotoxic carcinogen NDEA, the tumor promoting agent BHT or the hepatotoxin paracetamol. Tumor growth was investigated between the ages of 4 to 8.5 months and contrast-enhanced µCT imaging detected liver lesions as well as metastatic spread with high sensitivity and accuracy as confirmed by histopathology. Significant differences in the onset of tumor growth, tumor load and glucose metabolism were observed when the NDEA treatment group was compared with any of the other treatment groups. NDEA treatment of c-Myc transgenic mice significantly accelerated tumor growth and caused metastatic spread of HCC in to lung but this treatment also induced primary lung cancer growth. In contrast, BHT and paracetamol did not promote hepatocarcinogenesis. CONCLUSIONS/SIGNIFICANCE: The present study evidences the accuracy of in vivo imaging in defining tumor growth, tumor load, lesion number and metastatic spread. Consequently, the application of in vivo imaging techniques to transgenic animal models may possibly enable short-term cancer bioassays to significantly improve hazard identification and follow-up examinations of different organs by non-invasive methods.

Imaging of the brain in polytraumatized patients comparing 64-row spiral CT with incremental (sequential) CT.

INTRODUCTION: Up to now, due to a better image quality, for brain imaging the substantially slower sequential examination mode has been preferred during CT in polytraumatized patients. We aimed to re-evaluate modern ultrafast 64-row spiral CT regarding image quality in brain imaging of polytraumatized patients. METHODS: In 30 polytraumatized patients, both 64-row spiral and sequential CT of the brain were performed within 24h. Retrospectively, two radiologists subjectively evaluated the delineation of the internal capsule, the pons, the medial rectus muscle of the orbita, the differentiation of grey/white matter, and the extent of artifacts at the inner skull. Image noise was also evaluated objectively. Statistics were performed using Cohen's kappa and a two-sided t-test. RESULTS: Perfect or clear agreements were noted regarding the delineation of the inner skull, the medial rectus muscle, the internal capsule, and grey/white matter differentiation. Due to beam hardening artifacts at the level of the pons, no agreement and no superiority of one of the CT-methods was noted. No differences were obtained regarding the objective evaluation of image noise. DISCUSSION: Image quality is generally equivalent. Since 64-row spiral CT can substantially save examination time we recommend to perform a spiral examination of the brain in polytraumatized patients.

Phantom and cadaver measurements of dose and dose distribution in micro-CT of the chest in mice.

BACKGROUND: Micro-computed tomography (CT) allows high-resolution imaging of the chest in mice for small animal research with a significant radiation dose applied. PURPOSE: To report on measurement of the applied radiation dose using different scan protocols in micro-CT of the chest in mice. MATERIAL AND METHODS: Repetitive dose measurements were performed for four different micro-CT protocols (with/without respiratory gating) and for micro-CT fluoroscopy used for chest imaging. Measurements were carried out using thermoluminescence dosimeters (TLD) in mouse cadavers and in a PMMA phantom allowing measurement of the radiation dose in the direct path of rays and assessment of scattered radiation. RESULTS: The dose measured inside and outside the chests of the cadavers varied between 190 und 210 mGy, respectively. The expected mean doses in mice in the direct path of rays for the four examined micro-CT protocols varied between 170 and 280 mGy. The mean values for 1 and 5 minutes of fluoroscopy were 17 mGy and 105 mGy, respectively. CONCLUSION: The measured dose values are similar to the dose values for micro-CT of the chest reported so far. A relevant dose can be delivered by micro-CT of the chest, which could possibly interact with small animal studies. Therefore, the applied dose for a specific protocol should be known and adverse radiation effects be considered.

Rescue from hemodialysis by late recanalization of renal artery occlusion.

We report on a patient with terminal renal insufficiency undergoing hemodialysis since four months. Imaging studies showed complete renal artery occlusion of a single kidney with collateral perfusion. Interventional recanalization of the renal artery was successful with a drop of serum creatinine from 1138 to 163 mol/l sparing the patient from further hemodialysis.

Micro-computed tomography of pulmonary fibrosis in mice induced by adenoviral gene transfer of biologically active transforming growth factor-ß1.

BACKGROUND: Micro-computed tomography (micro-CT) is a novel tool for monitoring acute and chronic disease states in small laboratory animals. Its value for assessing progressive lung fibrosis in mice has not been reported so far. Here we examined the importance of in vivo micro-CT as non-invasive tool to assess progression of pulmonary fibrosis in mice over time. METHODS: Pulmonary fibrosis was induced in mice by intratracheal delivery of an adenoviral gene vector encoding biologically active TGF-ß1 (AdTGF-ß1). Respiratory gated and ungated micro-CT scans were performed at 1, 2, 3, and 4 weeks post pulmonary adenoviral gene or control vector delivery, and were then correlated with respective histopathology-based Ashcroft scoring of pulmonary fibrosis in mice. Visual assessment of image quality and consolidation was performed by 3 observers and a semi-automated quantification algorithm was applied to quantify aerated pulmonary volume as an inverse surrogate marker for pulmonary fibrosis. RESULTS: We found a significant correlation between classical Ashcroft scoring and micro-CT assessment using both visual assessment and the semi-automated quantification algorithm. Pulmonary fibrosis could be clearly detected in micro-CT, image quality values were higher for respiratory gated exams, although differences were not significant. For assessment of fibrosis no significant difference between respiratory gated and ungated exams was observed. CONCLUSIONS: Together, we show that micro-CT is a powerful tool to assess pulmonary fibrosis in mice, using both visual assessment and semi-automated quantification algorithms. These data may be important in view of pre-clinical pharmacologic interventions for the treatment of lung fibrosis in small laboratory animals.

Teaching surgery, radiology and anatomy together: the mix enhances motivation and comprehension.

PURPOSE: Preclinical and clinical topics are often separated in medical education. For example, surgery and radiology are often taught much later than anatomy. The aim of this study was to establish and to evaluate an interdisciplinary course combining these closely related subjects to enhance medical comprehension. METHODS: Two tutorials each lasting one term were offered to second year medical students, in which clinical topics were implemented linking anatomy to surgical and radiological knowledge. A questionnaire was used to evaluate the success of this approach. RESULTS: The motivation of the students was above average and the practical work was done accurately. The students confirmed that the course improved anatomical comprehension (>95%) and that the learned matters were relevant for their future (90%). Furthermore, interest in the subjects was higher after the course (>85%). Critical suggestions were to extend the course and to include more topics. CONCLUSIONS: A mix of surgery, radiology and anatomy is a teaching concept, which leads to high acceptance and interest in medical students.

Semiautomated segmentation of pleural effusions in MDCT datasets.

RATIONALE AND OBJECTIVES: To develop and evaluate a novel algorithm for semiautomated segmentation and volumetry of pleural effusions in multidetector computed tomography (MDCT) datasets. MATERIALS AND METHODS: A seven-step algorithm for semiautomated segmentation of pleural effusions in MDCT datasets was developed, mainly using algorithms from the ITK image processing library. Semiautomated segmentation of pleural effusions was performed in 40 MDCT datasets of the chest (males = 22, females = 18, mean age: 56.7 +/- 19.3 years). The accuracy of the semiautomated segmentation as compared with a manual segmentation approach was quantified based on the differences of the segmented volumes, the degree of over-/undersegmentation, and the Hausdorff distance. The time needed for the semiautomated and the manual segmentation process were recorded and compared. RESULTS: The mean volume of the pleural effusions was 557.30 mL (+/- 477.27 mL) for the semiautomated and 553.19 (+/- 473.49 mL) for the manual segmentation. The difference was not statistically significant (Student t-test, P = .133). Regression analysis confirmed a strong relationship between the semiautomated algorithm and the gold standard (r(2) = 0.998). Mean overlap of the segmented areas was 79% (+/- 9.3%) over all datasets with moderate oversegmentation (22% +/- 9.3%) and undersegmentation (21% +/- 9.7%). The mean Hausdorff distance was 17.2 mm (+/- 8.35 mm). The mean duration of the semiautomated segmentation process with user interaction was 8.4 minutes (+/- 2.6 minutes) as compared to 32.9 minutes (+/- 17.4 minutes) for manual segmentation. CONCLUSION: The semiautomated algorithm for segmentation and volumetry of pleural effusions in MDCT datasets shows a high diagnostic accuracy when compared with manual segmentation.

Respiratory-triggered three-dimensional T2-weighted MR cholangiography after injection of gadoxetate disodium: is it still reliable?

PURPOSE: To test the null hypothesis that there is no quantitative or qualitative difference between respiratory-triggered three-dimensional (3D) T2-weighted magnetic resonance (MR) cholangiography performed before or after administration of gadoxetate disodium. MATERIALS AND METHODS: For this retrospective HIPAA-compliant dual-center study, institutional review board approval was obtained, and a waiver of informed consent was granted. Between July and December 2008, 60 patients (age range, 18-82 years) who were referred for liver MR imaging with gadoxetate disodium underwent respiratory-triggered 3D MR cholangiography before and immediately after completion of portal venous phase contrast material-enhanced T1-weighted MR imaging. Quantitative signal-to-noise ratio (SNR) measurements were obtained in the extrahepatic biliary tract in both MR cholangiographic data sets in each patient. Qualitative assessment was performed by four readers with a four-point scale to assess the depiction of extra- and intrahepatic ducts up to the third order. Statistical analysis consisted of a one-sided Wilcoxon signed rank test, with a P value of less than .05 indicating a significant difference. RESULTS: There was a significant decrease in mean SNR in the MR cholangiographic data set after injection of gadoxetate disodium. SNR was 96 + or - 50 [standard deviation] and 78 + or - 47 before and after contrast media administration, respectively (P < .0001). For all readers, qualitative differences were most obvious in the depiction of the common bile duct and second- and third-order biliary branches, with the precontrast MR cholangiographic data sets being preferred (P < .0001). Precontrast data sets were also significantly preferred in the assessment of the right and left hepatic ducts by all readers. CONCLUSION: Gadoxetate disodium adversely affects respiratory-triggered 3D MR cholangiography, both qualitatively and quantitatively. We recommend that such a sequence be performed before injection of gadoxetate disodium.

Informatics in radiology: sliding-thin-slab averaging for improved depiction of low-contrast lesions with radiation dose savings at thin-section CT.

Current multidetector computed tomography (CT) scanners allow volumetric data acquisition with thin-section collimations and overlapping section reconstructions. The resultant nearly isotropic data sets help minimize partial-volume averaging effects and are ideal for two- and three-dimensional postprocessing and software-assisted lesion detection and quantification. However, the section thickness, image noise, and radiation dose are closely related, and when one parameter must be altered to suit the clinical setting, the others may be affected. When the clinical purpose demands both high spatial resolution and low image noise (eg, for the detection of hypoattenuating lesions in organs such as the kidneys and liver), the necessary trade-off--an increase in the radiation dose to the patient--may be unacceptable. The application of a sliding-thin-slab averaging algorithm during image postprocessing and review helps overcome this limitation by reconstructing thicker sections with lower noise levels from thin-section data obtained with dose-saving protocols. In principle, a high noise level is acceptable in the initial reconstruction of the CT volume data set. During image review at the workstation, the section thickness can be interactively increased to minimize image noise and improve lesion detectability. The combination of thin-section scanning with thick-section display allows routine volumetric imaging without a general increase in radiation dose or a reduction in the detectability of low-contrast lesions. Supplemental material available at http://radiographics.rsna.org/lookup/suppl/doi:10.1148/rg.302096007/-/DC1.

Cleidocranial dysplasia (CCD) causing respiratory distress syndrome in a newborn infant. A case report.

Cleidocranial dysplasia (CCD), also known as Scheuthauer Marie-Sainton Syndrome, is a rare autosomal dominant inherited disorder, characterized by general retardation in bone ossification, hypoplastic clavicles and various craniofacial and dental abnormalities. Early diagnosis of CCD can be difficult, because the majority of craniofacial abnormalities become obvious only during adolescence. We present a rare case of CCD with neonatal manifestation and would like to promote the awareness of this rare disorder and the importance of early diagnosis.

F-18 FDG PET/CT showing bilateral breast involvement in acute myeloid leukemia relapse.

Isolated extramedullary relapse with involvement of the breasts by acute myeloid leukemia (AML) after allogeneic stem cell transplantation is an uncommon event. We here report the case of a 27-year-old female patient, who was diagnosed with high-risk AML (FAB M5, complex karyotype). Fourteen months after successful bone marrow transplantation, she presented with asymptomatic masses in both breasts. Ultrasound-guided biopsy was performed and histopathology revealed relapsing AML. F-18 FDG PET/CT was performed for whole-body staging and intense multifocal uptake was seen in both breasts and in the abdomen. Isolated extramedullary disease recurrence was confirmed by bone marrow biopsy.

F-18 2-fluoro-2-deoxy-glucose positron emission tomography/computed tomography for the detection of radicular and peripheral neurolymphomatosis: correlation with magnetic resonance imaging and ultrasound.

Neurolymphomatosis is an uncommon extranodal manifestation of non-Hodgkin lymphoma. It may mimic a broad variety of neurologic conditions which renders clinical diagnosis challenging. As blind nerve biopsy is invasive and may be false negative, surrogate criteria for the diagnosis of neurolymphomatosis have been proposed based on magnetic resonance imaging/computed tomography findings. However, these morphologic modalities may suffer from limited sensitivity. Recently, a few reports have been published that discuss a possible advantage of F-18 2-fluoro-2-deoxy-glucose positron emission tomography/computed tomography (F-18 FDG PET/CT) in these patients.We report the case of a 41-year-old man who presented with progressive tetraparesis and dysaesthesia, in which F-18 FDG PET/CT aided to the diagnosis of neurolymphomatosis due to a large B-cell lymphoma. The patient received chemotherapy (R-CHOP) and the neurologic symptoms were clearly regressive. Three months after the end of systemic chemotherapy the patient presented again with progressive neurologic symptoms. A second PET/CT was performed and demonstrated disease recurrence in the right testis as well as widespread neurolymphomatosis. Additional ultrasound and magnetic resonance imaging examinations were performed and confirmed infiltration of the left brachial plexus, the right femoral, and the right sciatic nerve.We present this case to support the hypothesis that F-18 FDG PET/CT is a valuable imaging modality in patients with suspected neurolymphomatosis. It allows one to accurately determine the extent of the disease in a single whole-body examination.

In vivo microCT quantification of lung tumor growth in SPC-raf transgenic mice.

Lung cancer is the most common cancer worldwide. Early detection might reduce morbidity. In this study we evaluate a microCT imaging algorithm to assess in-vivo tumour load and quantification of tumour growth in a transgenic disease model of lung adenocarcinomas. MicroCT was carried out with n=10 SPC-raf transgenic mice without gating in spontaneously breathing and isoflurane anaesthetised animals. Segmentation of the air-filled spaces was obtained using a region growing algorithm by 3 independent observers. Inter- and intra-observer variability of the algorithm was determined and compared against an alternative region growing algorithm. Due to the multiple very small tumor nodules that occur and the low signal-to-noise ratio direct volumetric measurement of solitary tumor nodules is not feasible. However, tumor growth can be assessed by measuring the decrease in the segmented volume of the aerated lung areas. The presented algorithm can thus be used to evaluate therapeutic efficacies of novel treatment strategies. The imaging algorithm allows in vivo quantification of lung tumor load and tumor growth in transgenic mice with an acceptable intra- and interobserver variability.

Combined microPET/CT for imaging of hepatocellular carcinoma in mice.

The EGF-transgenic mouse is a genetic model of hepatocellular carcinoma that allows for a comprehensive study of signal pathways, molecular interactions and the evaluation of novel therapeutic concepts. In this regard, non-invasive imaging tools for serial in-vivo monitoring of tumor load and growth are highly desirable. This study therefore aimed at demonstrating the feasibility of non-invasive in-vivo imaging of primary liver malignancies in mice using combined contrast-enhanced microCT and F-18 FDG microPET. In our murine disease model, microCT enabled imaging of primary liver tumors down to a lesional diameter of 0.9 mm. F-18 FDG tumor-to-non-tumor ratio of HCCs was observed to be dependent on lesion size and linked to overpression of glucose transporters and hexokinase isoenzymes as determined by gene expression studies. Histopathologic analyses indicated an increased cellular dedifferentiation with increase lesion size, as well.

Percutaneous interventions for treating ischemic complications of aortic dissection.

The aim of this study was to evaluate the role of percutaneous interventions in treating ischemia complicating aortic dissection. Forty-five patients with ischemia complicating aortic dissection were treated by balloon fenestration, true lumen stenting, angioplasty, or thrombolysis. Clinical and laboratory examinations were performed before and after intervention, and at the end of follow-up (median 37 months). Eighteen dissections were acute, 9 sub-acute, and 18 chronic. Mesenterohepatic ischemia resolved in 16 of 18 patients; lactate and SGOT values fell from 2.89 to 1.23 mmol/L (p=0.006) and from 165.9 to 59.7 U/L (p=0.034), respectively. In patients with renal ischemia, creatinine levels fell from 360.1 to 196.3 micromol/L (p=0.007) accompanied by a significant reduction in blood pressure. Limb-threatening ischemia resolved in three of four patients; in 21 claudicants, the mean walking distance improved from 272 to 1,283 m (p=0.001). Spinal ischemia resolved completely or partially in six of eight patients. Adjunctive surgical measures were necessary in six patients. Overall 30-day mortality in the 45 patients was 6.7%; all three deaths were in patients with acute dissections (mortality in this subgroup 16.7%). Ischemia complicating aortic dissection can be effectively treated by percutaneous interventions resulting in good early and mid-term outcomes.

Chronic thromboembolic pulmonary hypertension: evaluation with 64-detector row CT versus digital substraction angiography.

The aim of the study was to evaluate the role of 64-row CT in the diagnostic workup of patients with chronic thromboembolic pulmonary hypertension (CTEPH) using digital substraction angiography (DSA) as the method of diagnostic reference. CT and DSA studies of 27 patients (54 main, 162 lobar and 540 segmental arteries) with a clinical suspicion of CTEPH were included in this retrospective and blinded analysis. Axial images and multiplanar thin maximum intensity projections (MIPs) (3mm) were consequently used for exact image interpretation whereas additional reconstructed thick MIPs gave an overview of the entire vascular tree comparable to DSA. Sensitivity and specificity of CT regarding CTEPH-related pathological changes in general were 98.3% and 94.8% at main/lobar level and 94.1% and 92.9% at segmental level, respectively. Sensitivity and specificity of CT regarding the different pathological criteria of CTEPH (complete obstruction, intimal irregularities, bands and webs, indirect signs) were 88.9-100% and 96.1-100% at main/lobar level and 84.3-90.5% and 92-98.7% at segmental level, respectively. Our results show that CT is an accurate and reliable non-invasive alternative to conventional DSA in the diagnostic workup in patients with CTEPH.

Unilateral tibia vara in a toddler caused by focal fibrocartilaginous dysplasia.

Focal fibrocartilaginous dysplasia (FFCD) of the tibia is a rare tumor like lesion probably caused by a failure of differentiation in the pes anserinus area. The children usually present with unilateral tibia vara and conspicuous walking features. The radiographic appearance of FFCD is pathognomic. In most cases this benign condition undergoes spontaneous resolution. Curettage or corrective osteotomy is only indicated when the deformity is persistent or progressive. We report the case of a 14 months old toddler diagnosed with FFCD. The characteristic radiographic and MRI features are presented. Further, we present for the first time the sonographic appearance of FFCD.

Distal aortic surgery following arch replacement with a frozen elephant trunk.

OBJECTIVE: The frozen elephant trunk technique allows the repair of concomitant aortic arch and proximal descending aortic pathology in a single stage by using a hybrid prosthesis consisting of a vascular graft with a distal stented end. There are patients, however, who will require a second distal operation despite this new technique due to progression of their aortic disease. It has been unclear whether the presence of the stented segment of the hybrid prosthesis results in unexpected technical difficulties or possibly advantages for further vascular reconstruction. METHODS: Six patients out of our initial cohort of 39 treated with a hybrid prosthesis from 2001 through 2006 have since required an additional distal aortic reconstruction. Two received endoluminal stent grafts, four had extensive open replacements. RESULTS: There was no 30-day mortality, one patient died on day 133 having been discharged from hospital of an unrelated MRSA septicaemia. Complete thrombosis of the proximally covered aneurysm or the false lumen had occurred in all patients so that the replacements reached from the end of the stented portion of the hybrid prosthesis to the desired distal level. The operative approach proved to be facilitated by the hybrid prosthesis in terms of the necessary exposure and operative trauma. Postoperative recovery was uneventful as related to the hybrid prosthesis with few pulmonary complications and at least comparable to contemporary results for second stage elephant trunk procedures. CONCLUSIONS: The distal operative replacement of the aorta following a frozen elephant operation is safe and technically feasible. Early experience suggests that there is an advantage as compared to the conventional elephant technique in terms of intraoperative handling and postoperative recovery.

Comparison of 1.0 M gadobutrol and 0.5 M gadopentate dimeglumine-enhanced MRI in 471 patients with known or suspected renal lesions: results of a multicenter, single-blind, interindividual, randomized clinical phase III trial.

The purpose of this phase III clinical trial was to compare two different extracellular contrast agents, 1.0 M gadobutrol and 0.5 M gadopentate dimeglumine, for magnetic resonance imaging (MRI) in patients with known or suspected focal renal lesions. Using a multicenter, single-blind, interindividual, randomized study design, both contrast agents were compared in a total of 471 patients regarding their diagnostic accuracy, sensitivity, and specificity to correctly classify focal lesions of the kidney. To test for noninferiority the diagnostic accuracy rates for both contrast agents were compared with CT results based on a blinded reading. The average diagnostic accuracy across the three blinded readers ('average reader') was 83.7% for gadobutrol and 87.3% for gadopentate dimeglumine. The increase in accuracy from precontrast to combined precontrast and postcontrast MRI was 8.0% for gadobutrol and 6.9% for gadopentate dimeglumine. Sensitivity of the average reader was 85.2% for gadobutrol and 88.7% for gadopentate dimeglumine. Specificity of the average reader was 82.1% for gadobutrol and 86.1% for gadopentate dimeglumine. In conclusion, this study documents evidence for the noninferiority of a single i.v. bolus injection of 1.0 M gadobutrol compared with 0.5 M gadopentate dimeglumine in the diagnostic assessment of renal lesions with CE-MRI.