Influence of the Computer-Aided Decision Support System Design on Ultrasound-Based Breast Cancer Classification.

Automation of medical data analysis is an important topic in modern cancer diagnostics, aiming at robust and reproducible workflows. Therefore, we used a dataset of breast US images (252 malignant and 253 benign cases) to realize and compare different strategies for CAD support in lesion detection and classification. Eight different datasets (including pre-processed and spatially augmented images) were prepared, and machine learning algorithms (i.e., Viola-Jones; YOLOv3) were trained for lesion detection. The radiomics signature (RS) was derived from detection boxes and compared with RS derived from manually obtained segments. Finally, the classification model was established and evaluated concerning accuracy, sensitivity, specificity, and area under the Receiver Operating Characteristic curve. After training on a dataset including logarithmic derivatives of US images, we found that YOLOv3 obtains better results in breast lesion detection (IoU: 0.544 ± 0.081; LE: 0.171 ± 0.009) than the Viola-Jones framework (IoU: 0.399 ± 0.054; LE: 0.096 ± 0.016). Interestingly, our findings show that the classification model trained with RS derived from detection boxes and the model based on the RS derived from a gold standard manual segmentation are comparable (p-value = 0.071). Thus, deriving radiomics signatures from the detection box is a promising technique for building a breast lesion classification model, and may reduce the need for the lesion segmentation step in the future design of CAD systems.

Change of Apoptosis and Glucose Metabolism in Lung Cancer Xenografts during Cytotoxic and Anti-Angiogenic Therapy Assessed by Annexin V Based Optical Imaging and 18F-FDG-PET/CT.

Methods: For apoptosis imaging, the near-infrared probe Annexin Vivo750 was used in combination with fluorescence molecular tomography and microcomputed tomography (FMT/µCT). Glucose metabolism was assessed using 18F-FDG-PET/CT. Five groups of nude mice bearing lung cancer xenografts (A549) were investigated: (i) untreated controls and two groups after (ii) cytotoxic (carboplatin) or (iii) anti-angiogenic (sunitinib) treatment for four and nine days, respectively. Imaging data were validated by immunohistochemistry. Results: In response to carboplatin treatment, an inverse relation was found between the change in glucose metabolism and apoptosis in A549 tumors. Annexin Vivo showed a continually increasing tumor accumulation, while the tumor-to-muscle ratio of 18F-FDG continuously decreased during therapy. Immunohistochemistry revealed a significantly higher tumor apoptosis (p=0.007) and a minor but not significant reduction in vessel density only at day 9 of carboplatin therapy. Interestingly, during anti-angiogenic treatment there was an early drop in the tumor-to-muscle ratio between days 0 and 4, followed by a subsequent minor decrease (18F-FDG tumor-to-muscle-ratio: 1.9 ± 0.4; day 4: 1.1 ± 0.2; day 9: 1.0 ± 0.2; p=0.021 and p=0.001, respectively). The accumulation of Annexin Vivo continuously increased over time (Annexin Vivo: untreated: 53.7 ± 36.4 nM; day 4: 87.2 ± 53.4 nM; day 9: 115.1 ± 103.7 nM) but failed to display the very prominent early induction of tumor apoptosis that was found by histology already at day 4 (TUNEL: p=0.0036) together with a decline in vessel density (CD31: p=0.004), followed by no significant changes thereafter. Conclusion: Both molecular imaging approaches enable visualizing the effects of cytotoxic and anti-angiogenic therapy in A549 tumors. However, the early and strong tumor apoptosis induced by the anti-angiogenic agent sunitinib was more sensitively and reliably captured by monitoring of the glucose metabolism as compared to Annexin V-based apoptosis imaging.

[Does SARS-CoV-2 cause lung inflammation even in mild clinical courses? : A multicenter report from outpatient care]. / Verursacht SARS-CoV-2 auch bei milden klinischen Verläufen eine Lungenentzündung? : Ein Multicenterbericht aus der ambulanten Versorgung.

OBJECTIVE: In spring 2020 imaging findings of the lungs were found in several radiological practices and in outpatient clinic patients, which indicated acute or previous viral pneumonia. It was striking that many of the patients affected had only mild symptoms. In this case study it was investigated to what extent SARS-CoV­2 can cause lung involvement even with minor symptoms. MATERIAL AND METHODS: In this study five outpatient radiological centers and two inpatient hospitals in North Rhine-Westphalia and Baden-Württemberg in Germany were involved. The retrospective analysis included outpatients with radiologically detected viral pneumonia, who were examined in March or April 2020. The clinical symptoms were divided into severity levels 1-5 using a simplified clinical score. The lung images were evaluated with respect to features specific for COVID-19 . The presence of a SARS-CoV­2 infection was verified using PCR, antibody testing and/or typical computed tomography (CT) morphology. RESULTS: A total of 50 patients were included, all of whom had radiological signs of viral pneumonia. The majority had no or only few non-specific symptoms (26/50). This was followed by mild symptoms of a flu-like infection (17/50). Severe forms were rare in outpatients (7/50). Detection of COVID-19 was successful in 30/50 cases using PCR and in 4/50 cases using an antibody test. In 16/50 cases the diagnosis was based on typical CT criteria and on the typical COVID patient history. CONCLUSION: A SARS-CoV­2 infection leads to lung involvement more often than previously assumed, namely not only in severely ill hospitalized patients but also in cases with only mild or even non-specific symptoms.

Structured Reporting of Solid and Cystic Pancreatic Lesions in CT and MRI: Consensus-Based Structured Report Templates of the German Society of Radiology (DRG). / Strukturierte Befundung von soliden und zystischen Pankreasläsionen im CT und MRT: Konsensus-basierte Befundvorlagen der Deutschen Röntgengesellschaft (DRG).

BACKGROUND: Radiological reports of pancreatic lesions are currently widely formulated as free texts. However, for optimal characterization, staging and operation planning, a wide range of information is required but is sometimes not captured comprehensively. Structured reporting offers the potential for improvement in terms of completeness, reproducibility and clarity of interdisciplinary communication. METHOD: Interdisciplinary consensus finding of structured report templates for solid and cystic pancreatic tumors in computed tomography (CT) and magnetic resonance imaging (MRI) with representatives of the German Society of Radiology (DRG), German Society for General and Visceral Surgery (DGAV), working group Oncological Imaging (ABO) of the German Cancer Society (DKG) and other radiologists, oncologists and surgeons. RESULTS: Among experts in the field of pancreatic imaging, oncology and pancreatic surgery, as well as in a public online survey, structured report templates were developed by consensus. These templates are available on the DRG homepage under www.befundung.drg.de and will be regularly revised to the current state of scientific knowledge by the participating specialist societies and responsible working groups. CONCLUSION: This article presents structured report templates for solid and cystic pancreatic tumors to improve clinical staging (cTNM, ycTNM) in everyday radiology. KEY POINTS: · Structured report templates offer the potential of optimized radiological reporting with regard to completeness, reproducibility and differential diagnosis.. · This article presents consensus-based, structured reports for solid and cystic pancreatic lesions in CT and MRI.. · These structured reports are available open source on the homepage of the German Society of Radiology (DRG) under www.befundung.drg.de.. CITATION FORMAT: · Persigehl T, Baumhauer M, Baeßler B et al. Structured Reporting of Solid and Cystic Pancreatic Lesions in CT and MRI: Consensus-Based Structured Report Templates of the German Society of Radiology (DRG). Fortschr Röntgenstr 2020; 192: 641 - 655.

Monitoring treatment effects in lung cancer-bearing mice: clinical CT and clinical MRI compared to micro-CT.

BACKGROUND: Compared to histology-based methods, imaging can reduce animal usage in preclinical studies. However, availability of dedicated scanners is limited. We evaluated clinical computed tomography (CT) and magnetic resonance imaging (MRI) in comparison to dedicated CT (micro-CT) for assessing therapy effects in lung cancer-bearing mice. METHODS: Animals received cisplatin (n = 10), sham (n = 12), or no treatment (n = 9). All were examined via micro-CT, CT, and MRI before and after treatment. Semiautomated tumour burden (TB) calculation was performed. The Bland-Altman, receiver operating characteristic (ROC), and Spearman statistics were used. RESULTS: All modalities always allowed localising and measuring TB. At all modalities, mice treated with cisplatin showed a TB reduction (p ≤ 0.012) while sham-treated and untreated individuals presented tumour growth (p < 0.001). Mean relative difference (limits of agreement) between TB on micro-CT and clinical scanners was 24.7% (21.7-27.7%) for CT and 2.9% (-4.0-9.8%) for MRI. Relative TB changes before/after treatment were not different between micro-CT and CT (p = 0.074) or MRI (p = 0.241). Mice with cisplatin treatment were discriminated from those with sham or no treatment at all modalities (p ≤ 0.001). Using micro-CT as reference standard, ROC areas under the curves were 0.988-1.000 for CT and 0.946-0.957 for MRI. TB changes were highly correlated across modalities (r ≥ 0.900, p < 0.001). CONCLUSIONS: Clinical CT and MRI are suitable for treatment response evaluation in lung cancer-bearing mice. When dedicated scanners are unavailable, they should be preferred to improve animal welfare.

Nilotinib Enhances Tumor Angiogenesis and Counteracts VEGFR2 Blockade in an Orthotopic Breast Cancer Xenograft Model with Desmoplastic Response.

Vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR)-targeted therapies predominantly affect nascent, immature tumor vessels. Since platelet-derived growth factor receptor (PDGFR) blockade inhibits vessel maturation and thus increases the amount of immature tumor vessels, we evaluated whether the combined PDGFR inhibition by nilotinib and VEGFR2 blockade by DC101 has synergistic therapy effects in a desmoplastic breast cancer xenograft model. In this context, besides immunohistological evaluation, molecular ultrasound imaging with BR55, the clinically used VEGFR2-targeted microbubbles, was applied to monitor VEGFR2-positive vessels noninvasively and to assess the therapy effects on tumor angiogenesis. DC101 treatment alone inhibited tumor angiogenesis, resulting in lower tumor growth and in significantly lower vessel density than in the control group after 14 days of therapy. In contrast, nilotinib inhibited vessel maturation but enhanced VEGFR2 expression, leading to markedly increased tumor volumes and a significantly higher vessel density. The combination of both drugs led to an almost similar tumor growth as in the DC101 treatment group, but VEGFR2 expression and microvessel density were higher and comparable to the controls. Further analyses revealed significantly higher levels of tumor cell-derived VEGF in nilotinib-treated tumors. In line with this, nilotinib, especially in low doses, induced an upregulation of VEGF and IL-6 mRNA in the tumor cells in vitro, thus providing an explanation for the enhanced angiogenesis observed in nilotinib-treated tumors in vivo. These findings suggest that nilotinib inhibits vessel maturation but counteracts the effects of antiangiogenic co-therapy by enhancing VEGF expression by the tumor cells and stimulating tumor angiogenesis.

In situ validation of VEGFR-2 and α v ß 3 integrin as targets for breast lesion characterization.

Vascular endothelial growth factor receptor 2 (VEGFR-2) and α v ß 3 integrin are the most frequently addressed targets in molecular imaging of tumor angiogenesis. In preclinical studies, molecular imaging of angiogenesis has shown potential to detect and differentiate benign and malignant lesions of the breast. Thus, in this retrospective clinical study employing patient tissues, the diagnostic value of VEGFR-2, α v ß 3 integrin and vascular area fraction for the diagnosis and differentiation of breast neoplasia was evaluated. To this end, tissue sections of breast cancer (n = 40), pre-invasive ductal carcinoma in situ (DCIS; n = 8), fibroadenoma (n = 40), radial scar (n = 6) and normal breast tissue (n = 40) were used to quantify (1) endothelial VEGFR-2, (2) endothelial α v ß 3 integrin and (3) total α v ß 3 integrin expression, as well as (4) the vascular area fraction. Sensitivity and specificity to differentiate benign from malignant lesions were calculated for each marker by receiver operating characteristics (ROC) analyses. Whereas vessel density, as commonly used, did not significantly differ between benign and malignant lesions (AUROC: 0.54), VEGFR-2 and α v ß 3 integrin levels were gradually up-regulated in carcinoma versus fibroadenoma versus healthy tissue. The highest diagnostic accuracy for differentiating carcinoma from fibroadenoma was found for total α v ß 3 integrin expression (AUROC: 0.76), followed by VEGFR-2 (AUROC: 0.71) and endothelial α v ß 3 integrin expression (AUROC: 0.68). In conclusion, total α v ß 3 integrin expression is the best discriminator between breast cancer, fibroadenoma and normal breast tissue. With respect to vascular targeting and molecular imaging of angiogenesis, endothelial VEGFR-2 appeared to be slightly superior to endothelial α v ß 3 for differentiating benign from cancerous lesions.

Diagnosis of pulmonary embolism: conventional ventilation/perfusion SPECT is superior to the combination of perfusion SPECT and nonenhanced CT.

BACKGROUND: Ventilation/perfusion single-emission photon CT (V/P-SPECT) is widely used to detect pulmonary embolism (PE). Any pathological deficit on P-SPECT with a corresponding unremarkable V-SPECT is considered an embolism. This means that a deficit on P-SPECT with a corresponding deficit on the ventilation scan correlates with other lung pathologies such as pneumonia, bullous emphysema or tumor. In principle, it is possible to identify any of these lung pathologies on nonenhanced chest CT and so this technique has the potential to replace V-SPECT in the diagnosis of PE. Today, SPECT/CT hybrid imaging systems are increasingly applied in clinical routines. OBJECTIVES: We investigated whether embolism can be diagnosed using a combined P-SPECT/CT hybrid imaging approach without V-SPECT. METHODS: Ninety-three patients with clinically suspected embolism were investigated with standard V/P-SPECT and a nonenhanced CT scan on a combined SPECT/CT system. A diagnosis of embolism was based on V/P-SPECT (gold standard). P-SPECT/CT datasets were blinded and analyzed without any knowledge of the V-SPECT data. The accuracy of P-SPECT/CT was compared to the gold standard. RESULTS: Embolism was diagnosed in 24/93 patients using V/P-SPECT. In total, 57 lung lobes were affected. P-SPECT/CT significantly (p < 0.01) overdiagnosed embolism in nonaffected patients. In total, 36 cases with 88 affected lung lobes were shown. The sensitivity was 95.8%, the specificity 82.6%, the false-negative rate 4.2% and the false-positive rate 17.3%. CONCLUSIONS: Our results demonstrate that a nonenhanced CT scan in a novel hybrid imaging system cannot replace V-SPECT in the scintigraphy-based diagnosis of PE. V-SPECT increases specificity and reduces the number of false-positive results when compared to 'perfusion-only' SPECT/CT.

Influence of repetitive contrast agent injections on functional and molecular ultrasound measurements.

Quantitative contrast-enhanced ultrasound plays an important role in tumor characterization and treatment assessment. Besides established functional ultrasound techniques, ultrasound molecular imaging using microbubbles targeted to disease-associated markers is increasingly being applied in pre-clinical studies. Often, repeated injections of non-targeted or targeted microbubbles during the same imaging session are administered. However, the influence of repeated injections on the accuracy of the quantitative data is unclear. Therefore, in tumor-bearing mice, we investigated the influence of multiple injections of non-targeted microbubbles (SonoVue) on time to peak and peak enhancement in liver and tumor tissue and of vascular endothelial growth factor receptor 2 (VEGFR2)-targeted contrast agents (MicroMarker) on specific tumor accumulation. We found significantly decreasing values for time to peak and a tendency for increased values for peak enhancement after multiple injections. Repeated injections of VEGFR2-targeted microbubbles led to significantly increased tumor accumulation, which may result from the exposure of additional binding sites at endothelial surfaces caused by mechanical forces from destroyed microbubbles.

A low molecular weight zinc2+-dipicolylamine-based probe detects apoptosis during tumour treatment better than an annexin V-based probe.

OBJECTIVES: Molecular imaging of apoptosis is frequently discussed for monitoring cancer therapies. Here, we compare the low molecular weight phosphatidylserine-targeting ligand zinc2+-dipicolylamine (Zn2+-DPA) with the established but reasonably larger protein annexin V. METHODS: Molecular apoptosis imaging with the fluorescently labelled probes annexin V (750 nm, 36 kDa) and Zn2+-DPA (794 nm, 1.84 kDa) was performed in tumour-bearing mice (A431). Three animal groups were investigated: untreated controls and treated tumours after 1 or 4 days of anti-angiogenic therapy (SU11248). Additionally, µPET with 18 F-FDG was performed. Imaging data were displayed as tumour-to-muscle ratio (TMR) and validated by quantitative immunohistochemistry. RESULTS: Compared with untreated control tumours, TUNEL staining indicated significant apoptosis after 1 day (P < 0.05) and 4 days (P < 0.01) of treatment. Concordantly, Zn2+-DPA uptake increased significantly after 1 day (P < 0.05) and 4 days (P < 0.01). Surprisingly, annexin V failed to detect significant differences between control and treated animals. Contrary to the increasing uptake of Zn2+-DPA, 18 F-FDG tumour uptake decreased significantly at days 1 (P < 0.05) and 4 (P < 0.01). CONCLUSIONS: Increase in apoptosis during anti-angiogenic therapy was detected significantly better with the low molecular weight probe Zn2+-DPA than with the annexin V-based probe. Additionally, significant treatment effects were detectable as early using Zn2+-DPA as with measurements of the glucose metabolism using 18 F-FDG. KEY POINTS: • The detection of apoptosis by non-invasive imaging is important in oncology. • A new low molecular weight probe Zn2+-DPA shows promise in depicting anti-angiogenic effects. • The small Zn2+-DPA ligand appears well suited for monitoring therapy. • Treatment effects are detectable just as early with Zn2+-DPA as with 18F-FDG.

Recent advances in molecular, multimodal and theranostic ultrasound imaging.

Ultrasound (US) imaging is an exquisite tool for the non-invasive and real-time diagnosis of many different diseases. In this context, US contrast agents can improve lesion delineation, characterization and therapy response evaluation. US contrast agents are usually micrometer-sized gas bubbles, stabilized with soft or hard shells. By conjugating antibodies to the microbubble (MB) surface, and by incorporating diagnostic agents, drugs or nucleic acids into or onto the MB shell, molecular, multimodal and theranostic MBs can be generated. We here summarize recent advances in molecular, multimodal and theranostic US imaging, and introduce concepts how such advanced MB can be generated, applied and imaged. Examples are given for their use to image and treat oncological, cardiovascular and neurological diseases. Furthermore, we discuss for which therapeutic entities incorporation into (or conjugation to) MB is meaningful, and how US-mediated MB destruction can increase their extravasation, penetration, internalization and efficacy.

Prognostic relevance of (18)F-FDG PET/CT in carcinoma of unknown primary.

OBJECTIVES: The aim of this study was to assess whether F-FDG PET combined with x-ray CT (F-FDG PET/CT) findings have a prognostic impact in patients with carcinoma of unknown primary (CUP). PATIENTS AND METHODS: Seventy patients with CUP who were referred for F-FDG PET/CT were included. F-FDG PET/CT results were checked against available histologic diagnosis and follow-up data. For each patient, the SUVmax of the lesion with maximum uptake was measured. RESULTS: In 26% of the patients, a primary tumor was identified. The follow-up period after F-FDG PET/CT scan ranged between 3 and 45 months. Kaplan-Meier analysis revealed 1-year survival rates of 92% in the group without evidence of malignancy on F-FDG PET/CT, 78% in the group with locoregional disease, and 34% in the group with extensive disease on F-FDG PET/CT. Three-year survival rates in these groups were 73%, 71%, and 23%, respectively (P = 0.001). There was no significant survival difference between patients with regionally confined disease without identification of the primary tumor and those in whom the primary tumor was identified on F-FDG PET/CT (P = 0.25). This was also the case for patients with extensive disease (P = 0.26). The SUVmax of the lesion with maximum uptake was not significantly related to survival (P = 0.56). CONCLUSIONS: F-FDG PET/CT is a helpful tool for the identification of the primary tumor in patients with CUP; it is also able to provide an accurate assessment of prognosis based on the extent of the disease without the need for identification of the primary tumor.

Ultrasound molecular imaging of E-selectin in tumor vessels using poly n-butyl cyanoacrylate microbubbles covalently coupled to a short targeting peptide.

OBJECTIVES: The purposes of this study were the development and preclinical evaluation of clinically translatable E-selectin-specific ultrasound contrast agents based on a peptide ligand with the recognition sequence IELLQAR. MATERIALS AND METHODS: The E-selectin-specific peptide was synthesized through solid phase peptide synthesis and covalently attached to poly n-butylcyanoacrylate-stabilized microbubbles with an air core. Quantification of the microbubble surface coverage with peptides was performed through flow cytometry. Targeted adhesion of peptide-coated microbubbles was investigated in vitro using parallel plate flow chamber assays on tumor necrosis factor-α-stimulated human umbilical vein endothelial cells. In vivo imaging was performed in nude mice bearing human ovarian carcinoma xenografts (MLS), followed by ex vivo immunohistochemistry validation of E-selectin expression. RESULTS: Success of peptide synthesis was validated through preparative reverse phase high-pressure liquid chromatography and electronspray ionization-mass spectrometry. Results of the flow cytometry revealed approximately 4000 E-selectin-specific peptides/microbubble surface. Results of the in vitro experiments demonstrated the specificity of peptide-coated microbubbles to E-selectin (1.10 ± 0.48 vs 0.19 ± 0.09 bound microbubbles per cell, before and after competition respectively; P < 0.01). The in vivo imaging enabled specific assessment of E-selectin expression in MLS carcinoma xenografts (5.21 ± 3.41 vs 1.37 ± 0.67 contrast intensity before and after competition, respectively; P < 0.05). CONCLUSIONS: Clinically translatable microbubbles that were covalently coupled to the short E-selectin-specific peptide (IELLQAR) enabled specific imaging of the E-selectin expression in tumor vessels in vivo.

The influence of different contrast medium concentrations and injection protocols on quantitative and clinical assessment of FDG-PET/CT in lung cancer.

OBJECTIVES: To compare the effects of two different contrast medium concentrations for use in computed X-ray tomography (CT) employing two different injection protocols on positron emission tomography (PET) reconstruction in combined 2-(18)F-desoxyglucose (FDG) PET/CT in patients with a suspicion of lung cancer. METHODS: 120 patients with a suspicion of lung cancer were enrolled prospectively. PET images were reconstructed with the non-enhanced and venous phase contrast CT obtained after injection of iopromide 300 mg/ml or 370 mg/ml using either a fixed-dose or a body surface area adapted injection protocol. Maximum and mean standardized uptake values (SUV(max) and SUV(mean)) and contrast enhancement (HU) were determined in the subclavian vein, ascending aorta, abdominal aorta, inferior vena cava, portal vein, liver and kidney and in the suspicious lung lesion. PET data were evaluated visually for the presence of malignancy and image quality. RESULTS: At none of the sites a significant difference in the extent of the contrast enhancement between the four different protocols was found. However, the variability of the contrast enhancement at several anatomical sites was significantly greater in the fixed dose groups than in the BSA groups for both contrast medium concentrations. At none of the sites a significant difference was found in the extent of the SUV(max) and SUV(mean) increase as a result of the use of the venous phase contrast enhanced CT for attenuation. Visual clinical evaluation of lesions showed no differences between contrast and non-contrast PET/CT (P=0.32). CONCLUSIONS: Contrast enhanced CT for attenuation correction in combined PET/CT in lung cancer affects neither the clinical assessment nor image quality of the PET-images. A body surface adapted contrast medium protocol reduces the interpatient variability in contrast enhancement.

Simultaneous dual-isotope SPECT/CT with (99m)Tc- and (111)In-labelled albumin microspheres in treatment planning for SIRT.

OBJECTIVES: To investigate simultaneous dual-isotope SPECT/CT with two differently radioisotope-labelled albumin-microsphere fractions for treatment planning of hepatic radioembolisation. METHODS: In addition to (99m)Technetium-labelled albumin microspheres (commercially available), we performed labelling with (111)Indium. Binding stability of (111)Indium-labelled microspheres was tested in vitro and in vivo in mice. Simultaneous dual-isotope SPECT/CT imaging was validated in an anthropomorphic torso phantom; subsequently, dual-isotope SPECT/CT was performed under in-vivo conditions in pigs (n = 3) that underwent transarterial injection of (99m)Technetium- and (111)Indium-labelled microspheres in the liver (right and left hepatic artery, respectively), in both kidneys and in the gluteal musculature. In total, n = 18 transarterial injections were performed. RESULTS: In-vitro testing and in-vivo studies in mice documented high binding stability for both (99m)Technetium-labelled and (111)Indium-labelled microsphere fractions. In phantom studies, simultaneous dual-isotope SPECT/CT enabled reliable separation of both isotopes. In pigs, the identified deposition of both isotopes could be accurately matched with intended injection targets (100 %, 18/18 intended injection sites). Furthermore, an incidental deposition of (99m)Technetium-labelled microspheres in the stomach could be correlated to the test injection into a right hepatic artery. CONCLUSION: Simultaneous dual-isotope SPECT/CT after transarterial injection with (99m)Technetium- and (111)Indium-labelled microspheres is feasible. Thus, it may offer additional, valuable information compared to single (99m)Technetium-labelled albumin examinations. KEY POINTS: • Simultaneous dual-isotope SPECT/CT with (111) In- and (99m) Tc-labelled albumin microspheres is feasible. • Differentiation of two microsphere fractions after transarterial injection is possible. • The origin of an extra-hepatic microsphere deposition can be correlated to the corresponding artery. • This technique could reduce the setup time for selective internal radiation treatment.

Identification of the iodine concentration that yields the highest intravascular enhancement in MDCT angiography.

OBJECTIVE: The objective of our study was to identify the iodine concentration that yields the highest intravascular contrast enhancement in MDCT angiography by intraindividual comparison in an animal model. MATERIALS AND METHODS: Six pigs underwent repeated chest MDCT examinations under standardized conditions using the same contrast medium (iopromide) with different iodine concentrations (150, 240, 300, and 370 mg I/mL). The contrast injection protocol was adapted to ensure an identical iodine delivery rate of 1.5 g I/s and the same total iodine dose of 300 mg/kg of body weight for all studies. Dynamic CT scans were acquired at the levels of the pulmonary artery and the ascending and descending aorta. Pulmonary and aortic peak enhancement values as well as time to peak (TTP) were calculated from time-enhancement curves. RESULTS: Pulmonary and aortic peak contrast enhancement values were significantly higher with the 240 and 300 mg I/mL contrast media than the 150 and 370 mg I/mL contrast media (e.g., ascending aorta: 240 vs 150, p = 0.0070; 300 vs 150, p = 0.0096; 240 vs 370, p = 0.0262; 300 vs 370, p = 0.0079). TTP values tended to be lower for the 150 mg I/mL contrast medium than for the contrast media with higher iodine concentrations. CONCLUSION: Comparison of contrast media with iodine concentrations ranging from 150 to 370 mg I/mL showed that contrast enhancement was significantly improved with the use of 240 and 300 mg I/mL contrast media given a fixed identical iodine delivery and normalized total iodine load in a porcine model. Contrast media with a moderate iodine concentration are most suitable for obtaining the highest intravascular contrast enhancement in CT angiography.

Accuracy of a clinical PET/CT vs. a preclinical µPET system for monitoring treatment effects in tumour xenografts.

PURPOSE: Small animal imaging is of growing importance for preclinical research and drug development. Tumour xenografts implanted in mice can be visualized with a clinical PET/CT (cPET); however, it is unclear whether early treatment effects can be monitored. Thus, we investigated the accuracy of a cPET versus a preclinical µPET using (18)F-FDG for assessing early treatment effects. MATERIALS AND METHODS: The spatial resolution and the quantitative accuracy of a clinical and preclinical PET were evaluated in phantom experiments. To investigate the sensitivity for assessing treatment response, A431 tumour xenografts were implanted in nude mice. Glucose metabolism was measured in untreated controls and in two therapy groups (either one or four days of antiangiogenic treatment). Data was validated by γ-counting of explanted tissues. RESULTS: In phantom experiments, cPET enabled reliable separation of boreholes≥5mm whereas µPET visualized boreholes≥2mm. In animal studies, µPET provided significantly higher tumour-to-muscle ratios for untreated control tumours than cPET (3.41±0.87 vs. 1.60±.0.28, respectively; p<0.01). During treatment, cPET detected significant therapy effects at day 4 (p<0.05) whereas µPET revealed highly significant therapy effects even at day one (p<0.01). Correspondingly, γ-counting of explanted tumours indicated significant therapy effects at day one and highly significant treatment response at day 4. Correlation with γ-counting was good for cPET (r=0.74; p<0.01) and excellent for µPET (r=0.85; p<0.01). CONCLUSION: Clinical PET is suited to investigate tumour xenografts≥5mm at an advanced time-point of treatment. For imaging smaller tumours or for the sensitive assessment of very early therapy effects, µPET should be preferred.

Liver dysplasia: US molecular imaging with targeted contrast agent enables early assessment.

PURPOSE: To investigate the ability of vascular endothelial growth factor receptor type 2 (VEGFR2)-targeted ultrasonographic (US) microbubbles for the assessment of liver dysplasia in transgenic mice. MATERIALS AND METHODS: Animal experiments were approved by the governmental review committee. Nuclear factor-κB essential modulator knock-out mice with liver dysplasia and wild-type mice underwent liver imaging by using a clinical US system. Two types of contrast agents were investigated: nontargeted, commercially available, second-generation microbubbles (SonoVue) and clinically translatable PEGylated VEGFR2-targeted microbubbles (BR55). Microbubble kinetics was investigated over the course of 4 minutes. Targeted contrast material-enhanced US signal was quantified 5 minutes after injection. Competitive in vivo binding experiments with BR55 were performed in knock-out mice. Immunohistochemical and hematoxylin-eosin staining of liver sections was performed to validate the in vivo US results. Groups were compared by using the Mann-Whitney test. RESULTS: Peak enhancement after injection of SonoVue and BR55 did not differ in healthy and dysplastic livers (SonoVue, P = .46; BR55, P = .43). Accordingly, immunohistochemical findings revealed comparable vessel densities in both groups. The specificity of BR55 to VEGFR2 was proved by in vivo competition (P = .0262). While the SonoVue signal decreased similarly in healthy and dysplastic livers during the 4 minutes, there was an accumulation of BR55 in dysplastic livers compared with healthy ones. Furthermore, targeted contrast-enhanced US signal indicated a significantly higher site-specific binding of BR55 in dysplastic than healthy livers (P = .005). Quantitative immunohistologic findings confirmed significantly higher VEGFR2 levels in dysplastic livers (P = .02). CONCLUSION: BR55 enables the distinction of early stages of liver dysplasia from normal liver.

Evaluation of bone substitute materials: comparison of flat-panel based volume CT to conventional multidetector CT.

Over the last decade tissue engineering has emerged as a key factor in bone regeneration within the field of cranio-maxillofacial surgery. Despite this in vivo analysis of tissue-engineered-constructs to monitor bone rehabilitation are difficult to conduct. Novel high-resolving flat-panel based volume CTs (fp-VCT) are increasingly used for imaging bone structures. This study compares the potential value of novel fp-VCT with conventional multidetector CT (MDCT) based on a sheep sinus floor elevation model. Calcium-hydroxyapatite reinforced collagen scaffolds were populated with autologous osteoblasts and implanted into sheep maxillary sinus. After 8, 16 and 24 weeks MDCT and fp-VCT scans were performed to investigate the volume of the augmented area; densities of cancellous and compact bone were assessed as comparative values. fp-VCT imaging resulted in higher spatial resolution, which was advantageous when separating closely related anatomical structures (i.e. trabecular and compact bone, biomaterials). Fp-VCT facilitated imaging of alterations occurring in test specimens over time. fp-VCTs therefore displayed high volume coverage, dynamic imaging potential and superior performance when investigating superfine bone structures and bone remodelling of biomaterials. Thus, fp-VCTs may be a suitable instrument for intraoperative imaging and future in vivo tissue-engineering studies.