[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.

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.

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.

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.

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.

The high angiogenic activity in very early breast cancer enables reliable imaging with VEGFR2-targeted microbubbles (BR55).

OBJECTIVES: Tumour xenografts of well-discernible sizes can be examined well by molecular ultrasound. Here, we investigated whether very early breast carcinomas express sufficient levels of VEGFR2 for reliable molecular ultrasound imaging with targeted microbubbles. METHODS: MCF-7 breast cancer xenografts were orthotopically implanted in nude mice (n = 26). Tumours measuring from 4 mm(3) (2 mm diameter) up to 65 mm(3) (5 mm diameter) were examined with automated 3D molecular ultrasound using clinically translatable VEGFR2-targeted microbubbles (BR55). Additionally, the relative tumour blood volume was assessed with non-targeted microbubbles (BR38). In vivo ultrasound data were validated by quantitative immunohistochemistry. RESULTS: Very small lesions 2 mm in diameter showed the highest binding of VEGFR2-specific microbubbles. In larger tumours significantly less BR55 accumulated (p = 0.023). Nonetheless, binding of VEGFR2-targeted microbubbles was still high enough for imaging. The relative blood volume was comparable at all tumour sizes. Both findings were confirmed by immunohistochemistry. Additionally, a significantly enhanced number of large and mature vessels were detected with increasing tumour size (p < 0.01), explaining the decrease in VEGFR2 expression during tumour growth. CONCLUSIONS: 3D molecular ultrasound using BR55 is very well suited to depicting the angiogenic activity in very small breast lesions, suggesting its potential for detecting and characterising these lesions.

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.

PET/CT in lung cancer: Influence of contrast medium on quantitative and clinical assessment.

OBJECTIVES: To evaluate the influence of intravenous contrast medium and different contrast medium phases on attenuation correction, PET image quality and clinical staging in combined PET/CT in patients with a suspicion of lung cancer. METHODS: Sixty patients with a suspicion of lung cancer were prospectively enrolled for combined (18)F-FDG-PET/CT examination. PET images were reconstructed with non-enhanced and arterial and venous phase contrast CT. Maximum and mean standardised uptake values (SUVmax and SUVmean) and contrast enhancement (HU) were determined in the subclavian vein, ascending aorta, abdominal aorta, inferior vena cava, portal vein, liver and kidney and lung tumour. PET data were evaluated visually for clinical staging and image quality. RESULTS: SUVmax was significantly increased between contrast and non-contrast PET/CT at all anatomic sites (all P < 0.001). SUVmax was significantly increased for arterial PET/CT compared to venous PET/CT in the arteries (all P < 0.001). Venous PET/CT resulted in significantly higher SUVmax values compared to arterial PET/CT in the parenchymatous organs (all P < 0.05). Visual clinical evaluation of malignant lesions showed no differences between contrast and non-contrast PET/CT (P = 1.0). CONCLUSIONS: Contrast enhanced CT is suitable for attenuation correction in combined PET/CT in lung cancer; it affects neither the clinical assessment nor image quality of the PET images. KEY POINTS : • Positron emission tomography combined with computed tomography is now a mainstream investigation • There has been debate about whether CT contrast agents affect PET results • Contrast-enhanced CT is satisfactory for attenuation correction in lung cancer PET/CT • Multiphase CT does not affect PET; additional unenhanced CT is unnecessary • For quantitative follow-up PET analysis, an identical PET/CT protocol is required.

Development and validation of an intrinsic landmark-based gating protocol applicable for functional and molecular ultrasound imaging.

OBJECTIVES: To implement a retrospective intrinsic landmark-based (ILB) gating protocol for contrast-enhanced ultrasound (CEUS) and to compare its efficiency to non-gated, manually gated and extrinsically gated CEUS. METHODS: CEUS of the liver was performed in healthy mice (n = 5) and in NEMO knockout mice with dysplastic livers (n = 5). In healthy animals, first-pass kinetics of non-specific microbubbles was recorded. Knockout mice were analysed regarding retention of VEGFR2-specific microbubbles. For retrospective gating, a landmark which showed respiratory movement was encircled as a region of interest (ROI). During inspiration, the signal intensity within the ROI altered, which served as gating signal. To evaluate the accuracy, non-gated, extrinsically gated and ILB-gated time-intensity curves were created. For each curve, descriptive parameters were calculated and compared to the gold standard (manual frame-by-frame gating). RESULTS: No significant differences in the variation of ILB- and extrinsically gated time-intensity curves from the gold standard were observed. Non-gated data showed significantly higher variations. Also the variation of molecular ultrasound data was significantly lower for ILB-gated compared to non-gated data. CONCLUSION: ILB gating is a robust and easy method to improve data accuracy in functional and molecular ultrasound liver imaging. This technique can presumably be translated to contrast-enhanced ultrasound examinations in humans. KEY POINTS: • Quantitative analysis of the uptake of contrast agents during ultrasound is complex. • Intrinsic landmark-based gating (ILB) offers a simple implementable method for motion correction. • Results using ILB-gating are comparable to extrinsic gating using external biomonitoring devices. • Functional and molecular imaging of mobile organs will benefit from ILB gating.

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.

Virtual elastic sphere processing enables reproducible quantification of vessel stenosis at CT and MR angiography.

PURPOSE: To develop and evaluate a user-friendly tool to enable efficient, accurate, and reproducible quantification of blood vessel stenosis in computed tomographic (CT) and magnetic resonance (MR) angiographic data sets. MATERIALS AND METHODS: All clinical experiments were approved by the institutional review board, and informed patient consent was acquired. Animal experiments were approved by the governmental review committee on animal care. A virtual elastic sphere passes through a blood vessel specified by user-provided start and end points, and the adapting diameter over the course of the vessel is recorded. The program was tested in phantoms to determine the accuracy of diameter estimation, and it was applied in micro-CT data sets of mice with induced vessel stenosis. Dual-energy CT angiography and MR angiography were performed in 16 patients with carotid artery stenosis, and reproducibility and required reader time of this automated technique were compared with manual measurements. Additionally, the effect of dual-energy CT-based discrimination between iodine- and calcium-based enhancement was investigated. Differences between carotid artery diameters of mice and between automated and manual measurement durations were assessed with a paired t test. Reproducibility of stenosis scores was evaluated with the Fisher z test. RESULTS: Phantom diameters were determined with an average error of 0.094 mm. Diameters of normal and injured carotid arteries of mice were significantly different (P < .01). For patient data, automated interreader variability was significantly (P < .01) lower than manual intra- and interreader variability, while time efficiency was improved (P < .01). CONCLUSION: The virtual elastic sphere tool is applicable to CT, dual-energy CT, and MR angiography, and it improves reproducibility and efficiency over that achieved with manual stenosis measurements.

Molecular and functional ultrasound imaging in differently aggressive breast cancer xenografts using two novel ultrasound contrast agents (BR55 and BR38).

OBJECTIVES: To characterise clinically translatable long-circulating (BR38) and VEGFR2-targeted (BR55) microbubbles (MB) and to assess their ability to discriminate breast cancer models with different aggressiveness. METHODS: The circulation characteristics of BR38 and BR55 were investigated in healthy mice. The relative blood volume (rBV) of MDA-MB-231 (n = 5) or MCF-7 (n = 6) tumours was determined using BR38. In the same tumours in-vivo binding specificity of BR55 was tested and VEGFR2 expression assessed. Data validation included quantitative immunohistological analysis. RESULTS: BR38 had a longer blood half-life than BR55 (>600 s vs. 218 s). BR38-enhanced ultrasound showed greater vascularisation in MDA-MB-231 tumours (p = 0.022), which was in line with immunohistology (p = 0.033). In-vivo competitive binding experiments proved the specificity of BR55 to VEGFR2 (p = 0.027). Binding of BR55 was significantly higher in MDA-MB-231 than in MCF-7 tumours (p = 0.049), which corresponded with the VEGFR2 levels found histologically (p = 0.015). However, differences became smaller when normalising the levels of BR55 to the rBV. CONCLUSIONS: BR38 and BR55 are well suited to characterising and distinguishing breast cancers with different angiogenesis and aggressiveness. Long-circulating BR38 MB allow extensive 3-dimensional examinations of larger or several organs. BR55 accumulation faithfully reflects the VEGFR2 status in tumours and depicts even small differences in angiogenesis.

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.

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.

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.

Intrarenal artery delineation with ultra high resolution, flat panel based, volume computerized tomography: outer limits of spatial resolution.

PURPOSE: New methods of noninvasive high resolution imaging may improve the delineation of tumor microvessels and, thus, be of significant help in surgical planning and cost-effective monitoring of novel anti-angiogenic therapy. We determined the maximum delineation of intrarenal microvessels with a novel flat panel based volume computerized tomography system in an experimental setting. MATERIALS AND METHODS: We prospectively evaluated 13 porcine renal specimens for intrarenal vessel delineation using a prototype gantry based, flat panel, cone beam computerized tomography system. The gantry incorporates an array of a 40 x 30 cm(2) CsI amorphous silicon flat panel detector consisting of a 2,048 x 1,536 matrix. After catheterizing the renal artery with a 5Fr end hole catheter a contrast enhanced scan was performed using BaS as contrast medium at a dilution of 200 mg/ml. The diameter of all definable arterial branches was determined using a software tool based on Medical Imaging and Interaction Toolkit, allowing semi-automatic segmentation of the vessel tree. In step 1 the vessel tree is segmented by a 3-dimensional region growing algorithm. Following its medial axis the vessel tree is extracted and converted to a representation, including the diameter of the vessels. RESULTS: In each kidney an average +/- SD of 47,454 +/- 22,382 arterial branches could be delineated. The diameter of the branches was 0.029 (mean 0.032 +/- 0.0025) to 3.444 mm (mean 1.813 +/- 0.6139) with a median of 0.263 mm. Of visible intrarenal arteries 2.7% had a vessel diameter of 0.029 mm. CONCLUSIONS: Flat panel based volume computerized tomography can visualize intrarenal microvessels down to a diameter of 0.03 mm. It may improve the assessment of renal microvessel architecture in healthy patients and in those with pathological conditions.

Molecular profiling of angiogenesis with targeted ultrasound imaging: early assessment of antiangiogenic therapy effects.

Molecular ultrasound is capable of elucidating the expression of angiogenic markers in vivo. However, the capability of the method for volumetric "multitarget quantification" and for the assessment of antiangiogenic therapy response has rather been investigated. Therefore, we generated cyanoacrylate microbubbles linked to vascular endothelial growth factor receptor 2 (VEGFR2) and alphavbeta3 integrin binding ligands and quantified their accumulation in squamous cell carcinoma xenografts (HaCaT-ras-A-5RT3) in mice with the quantitative volumetric ultrasound scanning technique, sensitive particle acoustic quantification. Specificity of VEGFR2 and alphavbeta3 integrin binding microbubbles was shown, and changes in marker expression during matrix metalloproteinase inhibitor treatment were investigated. In tumors, accumulation of targeted microbubbles was significantly higher compared with nonspecific ones and could be inhibited competitively by addition of the free ligand in excess. Also, multimarker imaging could successfully be done during the same imaging session. Molecular ultrasound further indicated a significant increase of VEGFR2 and alphavbeta3 integrin expression during tumor growth and a considerable decrease in both marker densities after matrix metalloproteinase inhibitor treatment. Histologic data suggested that the increasing VEGFR2 and alphavbeta3 integrin concentrations in tumors during growth are related to an up-regulation of its expression by the endothelial cells, whereas its decrease under therapy is more related to the decreasing relative vessel density. In conclusion, targeted ultrasound appears feasible for the longitudinal molecular profiling of tumor angiogenesis and for the sensitive assessment of therapy effects in vivo.

Pharmacodynamics of streptavidin-coated cyanoacrylate microbubbles designed for molecular ultrasound imaging.

OBJECTIVES: To assess the pharmacodynamic behavior of cyanoacrylate, streptavidin-coated microbubbles (MBs) and to investigate their suitability for molecular ultrasound imaging. MATERIALS AND METHODS: Biodistribution of MBs was analyzed in tumor-bearing mice using gamma-counting, immunohistochemistry, flow cytometry, and ultrasound. Further, vascular endothelial growth factor receptor 2-antibody coupled MBs were used to image tumor neovasculature. RESULTS: After 1 minute >90% of MBs were cleared from the blood and pooled in the lungs, liver, and spleen. Subsequently, within 1 hour a decent reincrease of MB-concentration was observed in the blood. The remaining MBs were removed by liver and spleen macrophages. About 30% of the phagocytosed MBs were intact after 48 hours. Shell fragments were found in the kidneys only. No relevant MB-accumulation was observed in tumors. In contrast, vascular endothelial growth factor receptor 2-specific MBs accumulated significantly within the tumor vasculature (P < 0.05). CONCLUSIONS: The pharmacokinetic behavior of streptavidin-coated cyanoacrylate MBs has been studied. In this context, the low amount of MBs in tumors after >5 minutes is beneficial for specific targeting of angiogenesis.