A reporting and analysis framework for structured evaluation of COVID-19 clinical and imaging data.

The COVID-19 pandemic has worldwide individual and socioeconomic consequences. Chest computed tomography has been found to support diagnostics and disease monitoring. A standardized approach to generate, collect, analyze, and share clinical and imaging information in the highest quality possible is urgently needed. We developed systematic, computer-assisted and context-guided electronic data capture on the FDA-approved mint LesionTM software platform to enable cloud-based data collection and real-time analysis. The acquisition and annotation include radiological findings and radiomics performed directly on primary imaging data together with information from the patient history and clinical data. As proof of concept, anonymized data of 283 patients with either suspected or confirmed SARS-CoV-2 infection from eight European medical centers were aggregated in data analysis dashboards. Aggregated data were compared to key findings of landmark research literature. This concept has been chosen for use in the national COVID-19 response of the radiological departments of all university hospitals in Germany.

Pancreatic Atrophy in Hepatocellular Carcinoma Patients Receiving Long-Term Treatment with Sorafenib.

OBJECTIVE: To date, sorafenib is the only approved systemic therapy for advanced hepatocellular carcinoma (HCC). Pancreatic atrophy has recently been reported in 2 patients as a novel side effect after long-term sorafenib treatment. METHODS: We retrospectively analyzed clinical and radiological data of patients with advanced HCC with long-term treatment of sorafenib (median 279 days, range 153-826 days). Pancreata were semi-manually segmented section by section to calculate the pancreas volumes before and under sorafenib treatment. RESULTS: Sorafenib reduced pancreatic volume in 18/19 (95%) HCC patients with a mean pancreatic volume loss of 25% (p = 0.002). Pancreatic volume loss depended on the dose (r = 0.36) and exposure time of sorafenib (r = 0.35) and was detectable as early as after 3 months of sorafenib treatment and already after a cumulative sorafenib dose of <100 g. Median overall survival was 13.2 months (range 7.8-31.3 months) but did not correlate with sorafenib-induced pancreatic volume reduction (hazard ratio 1.002, 95% confidence interval 0.981-1.060, p = 0.24). CONCLUSION: We could confirm pancreatic atrophy as a novel adverse event of sorafenib therapy in HCC patients, correlating with sorafenib dose and exposure time.

Histogram analysis of iodine maps from dual energy computed tomography for monitoring targeted therapy of melanoma patients.

AIM: Iodine quantification with dual energy computed tomography (DECT) enables quantitative assessment of contrast medium uptake. Our purpose was to investigate patterns of enhancement under BRAF inhibitor therapy by performing histogram analyses (HAs) of iodine maps. MATERIALS & METHODS: A total of 11 stage IV melanoma patients (32 metastases) underwent DECT at baseline and at least one follow up. Iodine uptake and HAs including maximum HU value (MAX), mean HU value (MEAN) and standard deviation (STD) was calculated. RESULTS: For BRAF-responders MEAN, MAX and STD decreased significantly (p < 0.05). Nonresponder showed increasing MAX and STD for six out of seven lesions, while MEAN and Iodine uptake decreased (four) and increased (three). CONCLUSION: HA based on DECT enables a quantitative and functional criterion and contributes to accurate response assessment for promising targeted therapies.

The role of perfusion effects in monitoring of chemoradiotherapy of rectal carcinoma using diffusion-weighted imaging.

PURPOSE: The aim of this study was to characterize and understand the therapy-induced changes in diffusion parameters in rectal carcinoma under chemoradiotherapy (CRT). The current literature shows conflicting results in this regard. We applied the intravoxel incoherent motion model, which allows for the differentiation between diffusion (D) and perfusion (f) effects, to further elucidate potential underlying causes for these divergent reports. MATERIALS AND METHODS: Eighteen patients with primary rectal carcinoma undergoing preoperative CRT were examined before, during, and after neoadjuvant CRT using diffusion-weighted imaging. Using the intravoxel incoherent motion approach, f and D were extracted and compared with postoperative tumor downstaging and volume. RESULTS: Initial diffusion-derived parameters were within a narrow range (D1 = 0.94 ± 0.12 × 10(-3) mm(2)/s). At follow-up, D rose significantly (D2 = 1.18 ± 0.13 × 10(-3) mm(2)/s; P < 0.0001) and continued to increase significantly after CRT (D3 = 1.24 ± 0.14 × 10(-3) mm(2)/s; P < 0.0001). The perfusion fraction f did not change significantly (f1 = 9.4 ± 2.0%, f2 = 9.4 ± 1.7%, f3 = 9.5 ± 2.7%). Mean volume (V) decreased significantly (V1 = 16,992 ± 13,083 mm(3); V2 = 12,793 ± 8317 mm(3), V3 = 9718 ± 6154 mm(3)). T-downstaging (10:18 patients) showed no significant correlation with diffusion-derived parameters. CONCLUSIONS: Conflicting results in the literature considering apparent diffusion coefficient (ADC) changes in rectal carcinoma under CRT for patients showing T-downstaging are unlikely to be due to perfusion effects. Our data support the view that under effective therapy, an increase in D/ADC can be observed.

Computational fluid dynamics investigation of chronic aortic dissection hemodynamics versus normal aorta.

OBJECTIVES: To evaluate hemodynamic changes during aneurysmal dilatation in chronic type B aortic dissections compared to hemodynamic parameters in the healthy aorta with the use of computational fluid dynamics (CFD). METHODS: True lumen (TL)/false lumen (FL) dimensional changes, changes in total pressure (TP), and wall shear stress (WSS) were evaluated at follow-up (FU) compared to initial examination (IE) with transient CFD simulation with geometries derived from clinical image data and inflow boundary conditions from magnetic resonance images. The TL/FL pressure gradient between ascending and descending aorta (DAo) and maximum WSS at the site of largest dilatation was compared to values for the healthy aorta. RESULTS: Hemodynamic changes at site of largest FL dilatation included 77% WSS reduction and 69% TP reduction. Compared to the healthy aorta, pressure gradient between ascending and DAo was a factor of 1.4 higher in the TL and a factor of 1.5 in the FL and increased at FU (1.6 and 1.7, respectively). Maximum WSS at the site of largest dilatation was a factor of 3 lower than that for the healthy aorta at IE and decreased by more than a factor of 2 at FU. CONCLUSIONS: The FL dilatation at FU favorably reduced TP. In contrast, unfavorable increase in pressure gradient between ascending and DAo was observed with higher values than in the healthy aorta. Maximum WSS was reduced at the site of largest dilation compared to healthy aorta.

Malignant melanoma S3-guideline "diagnosis, therapy and follow-up of melanoma".

This first German evidence-based guideline for cutaneous melanoma was developed under the auspices of the German Dermatological Society (DDG) and the Dermatologic Cooperative Oncology Group (DeCOG) and funded by the German Guideline Program in Oncology. The recommendations are based on a systematic literature search, and on the consensus of 32 medical societies, working groups and patient representatives. This guideline contains recommendations concerning diagnosis, therapy and follow-up of melanoma. The diagnosis of primary melanoma based on clinical features and dermoscopic criteria. It is confirmed by histopathologic examination after complete excision with a small margin. For the staging of melanoma, the AJCC classification of 2009 is used. The definitive excision margins are 0.5 cm for in situ melanomas, 1 cm for melanomas with up to 2 mm tumor thickness and 2 cm for thicker melanomas, they are reached in a secondary excision. From 1 mm tumor thickness, sentinel lymph node biopsy is recommended. For stages II and III, adjuvant therapy with interferon-alpha should be considered after careful analysis of the benefits and possible risks. In the stage of locoregional metastasis surgical treatment with complete lymphadenectomy is the treatment of choice. In the presence of distant metastasis mutational screening should be performed for BRAF mutation, and eventually for CKIT and NRAS mutations. In the presence of mutations in case of inoperable metastases targeted therapies should be applied. Furthermore, in addition to standard chemotherapies, new immunotherapies such as the CTLA-4 antibody ipilimumab are available. Regular follow-up examinations are recommended for a period of 10 years, with an intensified schedule for the first three years.

Hypofractionated carbon ion therapy delivered with scanned ion beams for patients with hepatocellular carcinoma - feasibility and clinical response.

PURPOSE: Photon-based radiation therapy does currently not play a major role as local ablative treatment for hepatocellular carcinoma (HCC). Carbon ions offer distinct physical and biological advantages. Due to their inverted dose profile and the high local dose deposition within the Bragg peak, precise dose application and sparing of normal tissue is possible. Furthermore, carbon ions have an increased relative biological effectiveness (RBE) compared to photons. METHODS AND MATERIALS: A total of six patients with one or more HCC-lesions were treated with carbon ions delivered by the raster-scanning technique according to our clinical trial protocol. Diagnosis of HCC was confirmed by histology or two different imaging modalities (CT and MRI) according to the AASLD-guidelines. Applied fractionation scheme was 4 × 10 Gy(RBE). Correct dose application was controlled by in-vivo PET measurement of ß + -activity in the irradiated tissue shortly after treatment. RESULTS: Patients were observed for a median time period of 11.0 months (range, 3.4 - 12.7 months). Imaging studies showed a partial response in 4/7 lesions and a stable disease in 3/7 lesions in follow-up CT- and MRI scans. Local control was 100%. One patient with multifocal intrahepatic disease underwent liver transplantation 3 months after carbon ion therapy. During radiotherapy and the follow-up period no severe adverse events have occurred. CONCLUSIONS: We report the first clinical results of patients with HCC undergoing carbon ion therapy using the rasterscanning technique at our institution. All patients are locally controlled and experienced no higher toxicities in a short follow-up period. Further patients will be included in our prospective Phase-I clinical trial PROMETHEUS-01 (NCT01167374).

Therapy response assessment in metastatic melanoma patients treated with a BRAF inhibitor: adapted Choi criteria can reflect early therapy response better than does RECIST.

PURPOSE: Targeted therapy can lead to considerable tumor reduction and may result initially in altered tissue at constant tumor size. In this setting, Response Evaluation Criteria in Solid Tumors (RECIST) can be inadequate for assessing early treatment response. Choi-criteria combine both size and density measurements. Our purpose was to evaluate computed tomography (CT) images of melanoma patients under BRAF-inhibitor therapy according to Choi-criteria which were adapted to our study (aChoi). MATERIAL AND METHODS: Twelve patients (four male, eight female, mean age 49) with stage IV melanoma treated with a BRAF inhibitor were included. Response was assessed according to RECIST for 39 lesions in contrast-enhanced CT. Target volumes are semiautomatically segmented to calculate mean density for aChoi-criteria, thus using a two-dimensional nonstandardized region of interest could be prevented. RESULTS: Eight patients are RECIST responders. aChoi-criteria indicate therapy response earlier compared to RECIST in five of eight patients. In seven cases, tumor density in CT had decreased 8 weeks after therapy start, whereas in some cases tumor size diminished less or even increased. Response according to aChoi was diagnosed in seven patients who showed in RECIST-evaluation stable disease in five and partial response in two cases. Fifteen weeks after therapy start almost all patients within the aChoi responders were RECIST responders, too. Only one aChoi responder showed still stable disease in RECIST. CONCLUSION: Our initial data indicate that aChoi-criteria can reflect response to vemurafenib earlier compared to RECIST. This is of clinical significance as BRAF-inhibitors are cost-intensive targeted therapies and can cause severe side effects, so criteria for early therapy response have to be evaluated.

Quantitative therapy response assessment by volumetric iodine-uptake measurement: initial experience in patients with advanced hepatocellular carcinoma treated with sorafenib.

OBJECTIVES: To investigate the volumetric iodine-uptake (VIU) changes by dual-energy CT (DECT) in assessing the response to sorafenib treated hepatocellular carcinoma (HCC) patients, compared with AASLD (American Association for the Study of Liver Diseases) and Choi criteria. MATERIALS AND METHODS: Fifteen patients with HCC receiving sorafenib, monitored with contrast-enhanced DECT scans at baseline and a minimum of one follow-up (8-12 weeks) were retrospectively evaluated. 30 target lesions in total were analyzed for tumor response according to VIU and adapted Choi criteria and compared with the standard AASLD. RESULTS: According to AASLD criteria, 67% target lesions showed disease control: partial response (PR) in 3% and stable disease (SD) in 63%. 33% lesions progressed (PD). Disease control rate presented by VIU (60%) was similar to AASLD (67%) and Choi (63%) (P>0.05). For disease control group, change in mean VIU was from 149.5 ± 338.3mg to 108.5 ± 284.1mg (decreased 19.1 ± 42.9%); and for progressive disease group, change in mean VIU was from 163.7 ± 346.7 mg to 263.9 ± 537.2 mg (increased 230.5 ± 253.1%). Compared to AASLD (PR, 3%), VIU and Choi presented more PR (33% and 30%, respectively) in disease control group (P<0.05). VIU has moderate consistency with both AASLD (kappa=0.714; P<0.005) and Choi (kappa=0.648; P<0.005), while VIU showed a better consistency and correlation with AASLD (kappa=0.714; P<0.005; r=0.666, P<0.005) than Choi with AASLD (kappa=0.634, P<0.005; r=0.102, P=0.296). CONCLUSION: VIU measurements by DECT can evaluate the disease control consistent with the current standard AASLD. Measurements are semi-automatic and therefore easy and robust to apply. As VIU reflects vital tumor burden in HCC, it is likely to be an optimal tumor response biomarker in HCC.

Assessment of thoracic aortic conformational changes by four-dimensional computed tomography angiography in patients with chronic aortic dissection type b.

To characterize the heartbeat-related distension of dissected and non-dissected thoracic aortic segments in chronic aortic dissection type b (CADB) ECG-gated computed tomography angiography was performed in ten CADB patients. For 20 time points of the R-R interval, multiplanar reformations were taken at non-dissected (A, B) and dissected (C) aorta: ascending aorta (A), aortic vertex (B), 10 cm distal to left subclavian (Ct, true channel; Cf, false channel). Relative amplitudes of aortic area and major and minor axis diameter changes were quantified. Area amplitudes were 12.9 +/- 3.7%, 11.4 +/- 1.8%, 16.5 +/- 5.9% and 10.5 +/- 5.7% at A, B, Ct and Cf, respectively. Area amplitudes were significantly greater at Ct than at Cf and B (p < 0.05). Major axis diameter amplitudes were 7.7 +/- 1.9%, 6.2 +/- 1.3%, 5.9 +/- 2.0% and 6.1 +/- 3.6% at A, B, Ct and Cf, respectively. There were no differences in major axis diameter amplitudes. Minor axis diameter amplitudes were 6.7 +/- 2.1%, 8.4 +/- 1.9%, 12.7 +/- 6.3% and 6.0 +/- 2.2% at A, B, Ct and Cf, respectively. Minor axis diameter amplitudes were significantly the greatest at Ct (p < 0.05). In CADB, the heartbeat-related distension of aortic area and diameter is evenly distributed over the non-dissected aortic arch. As a result from different blood flow properties, there are significantly greater conformational changes in the true channel of the dissected aorta.

Heartbeat-related displacement of the thoracic aorta in patients with chronic aortic dissection type B: quantification by dynamic CTA.

PURPOSE: The purpose of this study was to characterize the heartbeat-related displacement of the thoracic aorta in patients with chronic aortic dissection type B (CADB). MATERIALS AND METHODS: Electrocardiogram-gated computed tomography angiography was performed during inspiratory breath-hold in 11 patients with CADB: Collimation 16 mm x 1 mm, pitch 0.2, slice thickness 1mm, reconstruction increment 0.8 mm. Multiplanar reformations were taken for 20 equidistant time instances through both ascending (AAo) and descending aorta (true lumen, DAoT; false lumen, DAoF) and the vertex of the aortic arch (VA). In-plane vessel displacement was determined by region of interest analysis. RESULTS: Mean displacement was 5.2+/-1.7 mm (AAo), 1.6+/-1.0 mm (VA), 0.9+/-0.4 mm (DAoT), and 1.1+/-0.4mm (DAoF). This indicated a significant reduction of displacement from AAo to VA and DAoT (p<0.05). The direction of displacement was anterior for AAo and cranial for VA. CONCLUSION: In CADB, the thoracic aorta undergoes a heartbeat-related displacement that exhibits an unbalanced distribution of magnitude and direction along the thoracic vessel course. Since consecutive traction forces on the aortic wall have to be assumed, these observations may have implications on pathogenesis of and treatment strategies for CADB.

Motion characterization of aortic wall and intimal flap by ECG-gated CT in patients with chronic B-dissection.

RATIONALE AND OBJECTIVES: To evaluate whether dynamic computed tomography (CT)-imaging can provide functional vessel information in patients with chronic aortic dissection type Stanford-B (ADB). MATERIALS AND METHODS: In 32 patients, ECG-gated CT-angiography images were obtained. Cross-sectional area change and wall distensibility were investigated by semiautomatic vessel area segmentation at the end of aortic arch. Significance of distensibility differences was tested with regard to the aortic diameter, and the oscillation of the intimal flap was analyzed. RESULTS: The aorta could be segmented successfully in all patients. These were separated into three subgroups: (A) 6 patients with an aortic diameter <4 cm and without a visible intimal flap, (B) 9 patients with an aortic diameter <4 cm, and (C) 17 individuals with an aortic diameter > or = 4 cm; (B) and (C) having a visible intimal flap. Differences in distensibility between the subgroups were not significant. Overall mean distensibility was D(tot)=(1.3+/-0.6) x 10(-5) Pa(-1). Analysis of intimal flap oscillation showed a pulsatile short axis diameter decrease of the true lumen of up to 29%. CONCLUSION: Dynamic, ECG-gated CT-angiography can demonstrate pulsatile changes in aortic area and a highly variable motion of the intimal flap. Aortic distensibility appears independent of diameter or presence of a intimal flap. Follow-up studies may show correlation with possible complications.

Quantification of aortic distensibility in abdominal aortic aneurysm using ECG-gated multi-detector computed tomography.

RATIONALE AND OBJECTIVES: To detect distensibility changes that might be an indicator for an increased risk of rupture, cross-sectional area changes of abdominal aortic aneurysms (AAA) have been determined using ECG-gated CT. MATERIALS AND METHODS: Distensibility measurements of the aorta were performed in 67 patients with AAA. Time-resolved images were acquired with a four detector-row CT system using a modified CT-angiography protocol. Pulsatility-related cross-sectional area changes were calculated above and at AAA level by semiautomatic segmentation; distensibility values were obtained using additional systemic blood pressure measurements. Values were compared for small Ø<5 cm (n=44) and large Ø>5 cm (n=23) aneurysms. RESULTS: The aorta could be segmented successfully in all patients. Upstream AAA distensibility D was significantly higher than at AAA level for both groups: means above AAA (at AAA) D(above)=(1.3+/-0.8) x 10(-5) Pa(-1) (D(AAA )=(0.6+/-0.5) x 10(-5) Pa(-1)) t-test p(D)<0.0001. Differences of the distensibility between smaller and larger aneurysms were not found to be significant. CONCLUSION: Distensibility can be measured non-invasively with ECG-gated CT. The reduction of distensibility within aneurysms compared to normal proximal aorta is subtle; the lack of difference between both small and large aneurysms suggests that this reduction occurs early in the aneurysm's development. Hence, reduced distensibility might be a predictive parameter in patients with high risk of aortic disease.

Representation of cerebral bridging veins in infants by postmortem computed tomography.

The postmortem diagnosis of shaken baby syndrome, a severe form of child abuse, may be difficult, especially when no other visible signs of significant trauma are obvious. An important finding in shaken baby syndrome is subdural haemorrhage, typically originating from ruptured cerebral bridging veins. Since these are difficult to detect at autopsy, we have developed a special postmortem computed tomographic (PMCT) method to demonstrate the intracranial vein system in infants. This method is minimally invasive and can be carried out conveniently and quickly on clinical computed tomography (CT) systems. Firstly, a precontrast CT is made of the infant's head, to document the original state. Secondly, contrast fluid is injected manually via fontanel puncture into the superior sagittal sinus, followed by a repeat CT scan. This allows the depiction of even very small vessels of the deep and superficial cerebral veins, especially the bridging veins, without damaging them. Ruptures appear as extravasation of contrast medium, which helps to locate them at autopsy and examine them histologically, whenever necessary.

[Visualization of bridging veins by means of postmortem computed tomography]. / Darstellung der Brückenvenen mit der postmortalen Computertomographie.

At autopsy, visualization of lesions of the bridging veins, a frequent source of subdural bleeding, is difficult due to their anatomical localization. On the other hand their demonstration is of great importance for the assignment to a chronologically defined trauma. For this reason a postmortem method using computed tomography was developed to visualize the intracranial venous system by means of X-ray contrast media. In subdural bleedings, in which the skull had not been opened up, ruptured vessels could be accurately localized with this method, so that targeted dissection was possible during the subsequent autopsy.