Optimizing Coronary Computed Tomography Angiography Using a Novel Deep Learning-Based Algorithm.

Coronary computed tomography angiography (CCTA) is an essential part of the diagnosis of chronic coronary syndrome (CCS) in patients with low-to-intermediate pre-test probability. The minimum technical requirement is 64-row multidetector CT (64-MDCT), which is still frequently used, although it is prone to motion artifacts because of its limited temporal resolution and z-coverage. In this study, we evaluate the potential of a deep-learning-based motion correction algorithm (MCA) to eliminate these motion artifacts. 124 64-MDCT-acquired CCTA examinations with at least minor motion artifacts were included. Images were reconstructed using a conventional reconstruction algorithm (CA) and a MCA. Image quality (IQ), according to a 5-point Likert score, was evaluated per-segment, per-artery, and per-patient and was correlated with potentially disturbing factors (heart rate (HR), intra-cycle HR changes, BMI, age, and sex). Comparison was done by Wilcoxon-Signed-Rank test, and correlation by Spearman's Rho. Per-patient, insufficient IQ decreased by 5.26%, and sufficient IQ increased by 9.66% with MCA. Per-artery, insufficient IQ of the right coronary artery (RCA) decreased by 18.18%, and sufficient IQ increased by 27.27%. Per-segment, insufficient IQ in segments 1 and 2 decreased by 11.51% and 24.78%, respectively, and sufficient IQ increased by 10.62% and 18.58%, respectively. Total artifacts per-artery decreased in the RCA from 3.11 ± 1.65 to 2.26 ± 1.52. HR dependence of RCA IQ decreased to intermediate correlation in images with MCA reconstruction. The applied MCA improves the IQ of 64-MDCT-acquired images and reduces the influence of HR on IQ, increasing 64-MDCT validity in the diagnosis of CCS.

Applicability of Gene Expression in Saliva as an Alternative to Blood for Biodosimetry and Prediction of Radiation-induced Health Effects.

As the great majority of gene expression (GE) biodosimetry studies have been performed using blood as the preferred source of tissue, searching for simple and less-invasive sampling methods is important when considering biodosimetry approaches. Knowing that whole saliva contains an ultrafiltrate of blood and white blood cells, it is expected that the findings in blood can also be found in saliva. This human in vivo study aims to examine radiation-induced GE changes in saliva for biodosimetry purposes and to predict radiation-induced disease, which is yet poorly characterized. Furthermore, we examined whether transcriptional biomarkers in blood can also be found equivalently in saliva. Saliva and blood samples were collected in parallel from radiotherapy (RT) treated patients who suffered from head and neck cancer (n = 8) undergoing fractioned partial-body irradiations (1.8 Gy/fraction and 50-70 Gy total dose). Samples were taken 12-24 h before first irradiation and ideally 24 and 48 h, as well as 5 weeks after radiotherapy onset. Due to the low quality and quantity of isolated RNA samples from one patient, they had to be excluded from further analysis, leaving a total of 24 saliva and 24 blood samples from 7 patients eligible for analysis. Using qRT-PCR, 18S rRNA and 16S rRNA (the ratio being a surrogate for the relative human RNA/bacterial burden), four housekeeping genes and nine mRNAs previously identified as radiation responsive in blood-based studies were detected. Significant GE associations with absorbed dose were found for five genes and after the 2nd radiotherapy fraction, shown by, e.g., the increase of CDKN1A (2.0 fold, P = 0.017) and FDXR (1.9 fold increased, P = 0.002). After the 25th radiotherapy fraction, however, all four genes (FDXR, DDB2, POU2AF1, WNT3) predicting ARS (acute radiation syndrome) severity, as well as further genes (including CCNG1 [median-fold change (FC) = 0.3, P = 0.013], and GADD45A (median-FC = 0.3, P = 0.031)) appeared significantly downregulated (FC = 0.3, P = 0.01-0.03). A significant association of CCNG1, POU2AF1, HPRT1, and WNT3 (P = 0.006-0.04) with acute or late radiotoxicity could be shown before the onset of these clinical outcomes. In an established set of four genes predicting acute health effects in blood, the response in saliva samples was similar to the expected up- (FDXR, DDB2) or downregulation (POU2AF1, WNT3) in blood for up to 71% of the measurements. Comparing GE responses (PHPT1, CCNG1, CDKN1A, GADD45A, SESN1) in saliva and blood samples, there was a significant linear association between saliva and blood response of CDKN1A (R2 = 0.60, P = 0.0004). However, the GE pattern of other genes differed between saliva and blood. In summary, the current human in vivo study, (I) reveals significant radiation-induced GE associations of five transcriptional biomarkers in salivary samples, (II) suggests genes predicting diverse clinical outcomes such as acute and late radiotoxicity as well as ARS severity, and (III) supports the view that blood-based GE response can be reflected in saliva samples, indicating that saliva is a "mirror of the body" for certain but not all genes and, thus, studies for each gene of interest in blood are required for saliva.

Development of a Point-of-Care Microfluidic RNA Extraction Slide for Gene Expression Diagnosis after Irradiation.

In times of war, radiological/nuclear emergency scenarios have become a reemphasized threat. However, there are challenges in transferring whole-blood samples to laboratories for specialized diagnostics using RNA. This project aims to miniaturize the process of unwieldy conventional RNA extraction with its stationed technical equipment using a microfluidic-based slide (MBS) for point-of-care diagnostics. The MBS is thought to be a preliminary step toward the development of a so-called lab-on-a-chip microfluidic device. A MBS would enable early and fast field care combined with gene expression (GE) analysis for the prediction of hematologic acute radiation syndrome (HARS) severity or identification of RNA microbes. Whole blood samples from ten healthy donors were irradiated with 0, 0.5 and 4 Gy, simulating different ARS severity degrees. RNA quality and quantity of a preliminary MBS was compared with a conventional column-based (CB) RNA extraction method. GE of four HARS severity-predicting radiation-induced genes (FDXR, DDB2, POU2AF1 and WNT3) was examined employing qRT-PCR. Compared to the CB method, twice as much total RNA from whole blood could be extracted using the MBS (6.6 ± 3.2 µg vs. 12.0 ± 5.8 µg) in half of the extraction time, and all MBS RNA extracts appeared DNA-free in contrast to the CB method (30% were contaminated with DNA). Using MBS, RNA quality [RNA integrity number equivalent (RINe)] values decreased about threefold (3.3 ± 0.8 vs. 9.0 ± 0.4), indicating severe RNA degradation, while expected high-quality RINe ≥ 8 were found using column-based method. However, normalized cycle threshold (Ct) values, as well as radiation-induced GE fold-changes appeared comparable for all genes utilizing both methods, indicating that no RNA degradation took place. In summary, the preliminary MBS showed promising features such as: 1. halving the RNA extraction time without the burden of heavy technical equipment (e.g., a centrifuge); 2. absence of DNA contamination in contrast to CB RNA extraction; 3. reduction in blood required, because of twice the biological output of RNA; and 4. equal GE performance compared to CB, thus, increasing its appeal for later semi-automatic parallel field applications.

First assessment of flow phenomena of acute and chronic thrombosis in the jugular veins using new ultrasound vector-flow imaging.

AIM: First assessment of flow changes in the jugular veins using high resolution ultrasound vector flow. MATERIAL UND METHODS: 15 patients (8 males, 7 females) with an age range of 35 to 82 years (mean age 58.53±12.26 years) were examined by an experienced examiner using high power ultrasound equipment (Resona R9, Mindray) with probe technology (Mindray L9-3U Linear Array transducer, 2.5 to 9.0 MHz). This group was compared with five healthy subjects (mean age 35.4±13.79 years) as a reference. To assess flow changes, the color-coded duplex sonography and the novel vector flow technique were used. The evaluation was performed of vector morphology changes, turbulence, and wall resistance measurements. RESULTS: There were changes after acute and chronic thrombosis in 9 cases, and venous compression in 7 cases. Turbulence was measurable from 0.01 % to 64.44 %, the average turbulence was 19.73±22.06 %. Wall resistance measurement showed values from 0.01 Pa to 3.14 Pa, depending on the age of the thrombosis or compression. The reference veins showed turbulence of 0.94±1.5 % and a mean wall resistance of 0.05±0.05 Pa. There are statistically significant differences between normal and thrombotic or compressed veins in terms of maximum wall stress (p = 0.006) and mean degree of turbulence (p = 0.012), while the difference in mean wall stress is not statistically significant (p = 0.058). CONCLUSION: Despite still existing technical limitations, the combination of V-flow and wall stress measurements in jugular vein changes suggests a high diagnostic potential.

Advanced multimodal imaging of solid thyroid lesions with artificial intelligence-optimized B-mode, elastography, and contrast-enhanced ultrasonography parametric and with perfusion imaging: Initial results.

 Goal of the study was the assessment of AI-assisted diagnosis of solid thyroid foci with multimodal modern ultrasound imaging. 50 patients (26-81 years, 54.7±13.1 years) were included in the study. Multimodal ultrasound imaging by means of B-mode with linear probe (4-12 MHz) with option of automated documentation of findings by means of AI, with supplementary Ultra MicroAngiography (UMA) was used. Macrovascularisation was assessed by dynamic contrast ultrasonography (CEUS) with parametric evaluation and perfusion analysis, and microvascularization was assessed by combined strain and shear wave elastography on a novel high-performance ultrasound system (Resona R9/Mindray) by an experienced examiner with independent reading. The evaluation was performed according to TI-RADS III-V.The volume of the thyroid lobes on both sides averaged 39 ml±5 ml (27 to 69 ml). The 13 cases of histologically confirmed thyroid carcinomas (8 papillary, 2 medullary, 2 microfollicular, 1 anaplastic CA) with a mean size of 15 mm±6 mm (9-21 mm) were correctly evaluated by TI-RADS V on the basis of irregular shape, induration > 2.5 m/s or > 30kPA and striking wash-out kinetics. Tumor lymph nodes could only be correctly detected preoperatively in one case of medullary carcinoma according to the surgical findings, based on irregular vascularization with UMA in roundish shape with cortex > 4 mm, transverse diameter up to 11 mm. In 25 cases of inhomogeneous nodular goiter an evaluation with TI-RADS III was performed in 31 cases, in 4 cases with incomplete marginal contour, partial marginal vascularization with UMA and partial wash out with indurations up to 2.5 m/s 30 kPA an evaluation with TI-RADS IV and surgical excision for nodular goiter. In 12 cases regressive nodular changes without relevant malignancy criteria resulted in nodular goiter, with focal changes up to 1.5 cm in diameter, classified as requiring control with TI-RADS III. There were no relevant changes in findings in the controls after 6 months. From the AI tool, the 20/25 goiter nodes were assessed as TI-RADS III, 7/12 adenomas, 5 goiter nodes, and 5 adenomas as TI-RADS IV, 5/13 carcinomas as TI-RADS IV, and 8/13 carcinomas as TI-RADS V.Multimodal ultrasound diagnostics supported by AI has a high diagnostic potential for the evaluation of solid thyroid lesions and standardizes the reporting with digital representative image documentation. CEUS perfusion and modern elastography techniques allow targeted follow-up of TI-RADS III findings.

Gene Expression Changes in a Prefinal Health Stage of Lethally Irradiated Male and Female Rhesus Macaques.

Radiation-induced gene expression (GE) changes can be used for early and high-throughput biodosimetry within the first three days postirradiation. However, is the method applicable in situations such as the Alexander Litvinenko case or the Goiania accident, where diagnosis occurred in a prefinal health stage? We aimed to characterize gene expression changes in a prefinal health stage of lethally irradiated male and female rhesus macaques. Peripheral blood was drawn pre-exposure and at the prefinal stage of male and female animals, which did not survive whole-body exposure with 700 cGy (LD66/60). RNA samples originated from a blinded randomized Good Laboratory Practice study comprising altogether 142 irradiated rhesus macaques of whom 60 animals and blood samples (15 samples for both time points and sexes) were used for this analysis. We evaluated GE on 34 genes widely used in biodosimetry and prediction of the hematological acute radiation syndrome severity (H-ARS) employing quantitative real-time polymerase chain reaction (qRT-PCR). These genes were run in duplicate and triplicate and altogether 96 measurements per time point and sex could be performed. In addition, 18S ribosomal RNA (rRNA) was measured to depict the ribosome/transcriptome status as well as for normalization purposes and 16S rRNA was evaluated as a surrogate for bacteremia. Mean differential gene expression (DGE) was calculated for each gene and sex including all replicate measurements and using pre-exposure samples as the reference. From 34 genes, altogether 27 genes appeared expressed. Pre-exposure samples revealed no signs of bacteremia and 18S rRNA GE was in the normal range in all 30 samples. Regarding prefinal samples, 46.7% and 40% of animals appeared infected in females and males, respectively, and for almost all males this was associated with out of normal range 18S rRNA values. The total number of detectable GE measurements was sixfold (females) and 15-fold (males) reduced in prefinal relative to pre-exposure samples and about tenfold lower in 80% of prefinal compared to pre-exposure samples (P < 0.0001). An overall 11-fold (median) downregulation in prefinal compared to pre-exposure samples was identified for most of the 27 genes and even FDXR appeared 4-14-fold downregulated in contrast to a pronounced up-regulation according to cited work. This pattern of overall downregulation of almost all genes and the rapid reduction of detectable genes at a prefinal stage was found in uninfected animals with normal range 18S rRNA as well. In conclusion, in a prefinal stage after lethal radiation exposure, the ribosome/transcriptome status remains present (based on normal range 18S rRNA values) in 60-67% of animals, but the whole transcriptome activity in general appears silenced and cannot be used for biodosimetry purposes, but probably as an indicator for an emerging prefinal health stage.

Contrast enhanced ultrasonography (CEUS) a novel tool to detect intestinal epithelial barrier dysfunction in severe COVID-19 disease.

Ten patients with confirmed COVID-19 disease were studied. Nine patients required intensive care treatment, among them four needed extracorporeal membrane oxygenation (ECMO). Contrast enhanced ultrasonography (CEUS) was performed by one experienced investigator as a bolus injection of up to 2.4 ml of sulphur hexafluoride microbubbles via a central venous catheter. B-Mode evaluation and strain elastography showed mural edema of the small bowel with a thickness of up to 10 mm in all patients. We applied color coded Doppler sonography (CCDS) and power mode with flow-adapted parameters and early, dynamic capillary arterial contrast enhancement of bowel wall structures <10 s to assess perfusion of the small bowel. In all patients, reactive hyperemia was seen in the entire small bowel. In a subgroup of seven patients microbubbles translocated into the intestinal lumen. Thus, high-grade intestinal barrier disruption secondary to SARSCoV-2 infection can be postulated in these patients.This is the first description of perfusion changes and a disruption of the small bowel epithelial barrier in COVID-19 Patients using contrast ultrasonography and elastography.

Examining potential confounding factors in gene expression analysis of human saliva and identifying potential housekeeping genes.

Isolation of RNA from whole saliva, a non-invasive and easily accessible biofluid that is an attractive alternative to blood for high-throughput biodosimetry of radiological/nuclear victims might be of clinical significance for prediction and diagnosis of disease. In a previous analysis of 12 human samples we identified two challenges to measuring gene expression from total RNA: (1) the fraction of human RNA in whole saliva was low and (2) the bacterial contamination was overwhelming. To overcome these challenges, we performed selective cDNA synthesis for human RNA species only by employing poly(A)+-tail primers followed by qRT-PCR. In the current study, this approach was independently validated on 91 samples from 61 healthy donors. Additionally, we used the ratio of human to bacterial RNA to adjust the input RNA to include equal amounts of human RNA across all samples before cDNA synthesis, which then ensured comparable analysis using the same base human input material. Furthermore, we examined relative levels of ten known housekeeping genes, and assessed inter- and intra-individual differences in 61 salivary RNA isolates, while considering effects of demographical factors (e.g. sex, age), epidemiological factors comprising social habits (e.g. alcohol, cigarette consumption), oral hygiene (e.g. flossing, mouthwash), previous radiological diagnostic procedures (e.g. number of CT-scans) and saliva collection time (circadian periodic). Total human RNA amounts appeared significantly associated with age only (P ≤ 0.02). None of the chosen housekeeping genes showed significant circadian periodicity and either did not associate or were weakly associated with the 24 confounders examined, with one exception, 60% of genes were altered by mouthwash. ATP6, ACTB and B2M represented genes with the highest mean baseline expression (Ct-values ≤ 30) and were detected in all samples. Combining these housekeeping genes for normalization purposes did not decrease inter-individual variance, but increased the robustness. In summary, our work addresses critical confounders and provides important information for the successful examination of gene expression in human whole saliva.

Dynamic endoluminal contrast enhanced ultrasound (CEUS) for display of drainages in inflammatory abdominal fluid collections1.

AIM: To evaluate the additive clinical value of endoluminal contrast enhanced ultrasound (CEUS) after interventional placement of drainages in abdominal fluid collections. MATERIAL/METHOD: Examination of 30 patients using a 1-6 MHz convex probe (Resona 7, Mindray) to locate the fluid collection in B-Mode. Additionally, dynamic endoluminal CEUS with 1 ml sulphur-hexafluoride microbubbles was performed to measure the extent of the percutaneously drained abscesses. Independent assessment of dynamically stored images in PACS in DICOM format. Correlation to reference imaging using computed tomography (CT). RESULTS: A total of 30 patients were examined (17 m, 19-78 years, mean 56.1 years). Drainages were positioned in the liver in 15 cases, in the pelvis after kidney transplantation in 4 cases, close to the spleen in 1 case, and in the abdomen in 10 cases. In all cases abscesses showed marginal hyperaemia with reactive septations in CEUS. The drainage position was assessed by means of B-mode in all cases first and then by CEUS. In 4 cases CEUS showed a fistula to the pleura, in 5 cases to the peritoneum, in 2 cases to the intestine, in 5 cases to the biliary tract, corresponding to the CT. In 2 cases there was a hint of an anastomotic leakage after intestinal anastomosis, which was reliably detected by CT. The drainage was removed in 11 cases within a period of 2 to 5 days after CEUS control, in 9 cases within a period of 5 to 10 days. Another operation was necessary in 3 cases. A new drainage was placed in 2 cases. The required amount of ultrasound contrast medium is 1 ml endoluminally diluted to 9 ml sodium chloride. CONCLUSION: CEUS facilitates the exact localization and characterization of inflammatory abdominal fluid collections. Furthermore, possible fistulas can be detected that cannot be seen with conventional ultrasound.

Role of clinical and CT findings in the identification of adult small-bowel intussusception requiring surgical intervention.

BACKGROUND: In adults, intussusception has been considered traditionally to have an underlying aetiology. The aim of this study was to determine CT and clinical features of small-bowel intussusceptions that required surgical intervention. METHODS: Adult patients were identified in whom small-bowel intussusceptions were noted on CT images. The appearance, number, type (enteroenteric versus enterocolic), length and maximum short-axis diameter of intussusceptions, and presence of bowel obstruction (short-axis diameter of proximal small bowel greater than 3 cm) were analysed. The outcome was defined as surgical (complicated) or self-limiting (uncomplicated). Associations between complicated and uncomplicated intussusceptions and patient characteristics were investigated. RESULTS: Among 75 patients (56 male) with a mean age of 45 years, 103 intussusceptions were identified, of which 98 (95 per cent) were enteroenteric and 5 (5 per cent) enterocolic. Only 12 of 103 intussusceptions (12 per cent) in 12 of 75 (16 per cent) patients required surgical therapy and were considered to be complicated, with half of these having a neoplastic lead point. Length (P < 0.001), diameter (P < 0.001) and type (P = 0.002) of intussusception as well as presence of vessels (P = 0.023) within an intussusception on a CT scan, clinical symptoms (P = 0.007) and signs of bowel obstruction (P < 0.001) were associated with a surgical outcome. CONCLUSION: Clinical symptoms, signs of bowel obstruction, type and length of intussusception, and a visible tumour within an intussusception on CT scan were critical signs of complicated intussusception, requiring surgical intervention.

High-performance sonographical multimodal imaging of non cystic thyroid lesions: Chances of the preoperative diagnostics in relation to histopathology.

AIM: To improve preoperative diagnostics of solid non-cystic thyroid lesions by using new high-performance ultrasound techniques: optimized B-mode morphology, elastography, Color-Coded Doppler-Sonography (CCDS) and contrast enhanced ultrasound (CEUS)MATERIALS AND METHODS:In 33 cases solid, non-cystic thyroid lesions were rated as TIRADS 3 and up from conventional B-mode examinations. Additional high resolution Power Doppler including HR- and Glazing-Flow as optimized macrovascularization techniques, shear wave elastography and CEUS were performed on these patients by one experienced examiner. For CEUS a bolus of 1-2.4 ml Sulfurhexafluorid microbubbles (SonoVue®, Bracco, Milan, Italy) was injected into a cubital vein and then the distribution kinetics of the contrast agent were documented from the early arterial phase (10 to 15 seconds after injection) to the late venous phase (5 minutes after injection). Postoperative histopathology was the diagnostic gold standard as it provides the most reliable proof. RESULTS: 33 patients (13 males, 20 females; age 29 -77 years; mean 55 years; SD 13 years) were included in this study. 28 of them had benign regressive thyroid nodules, 3 had adenomas and 4 were diagnosed with carcinomas (3 were histologically identified as papillary thyroid carcinomas, one as a medullary thyroid carcinoma). The volume of the thyroid gland ranged from 6.6 to 401.3 cm2 (mean 72.6±92.0 cm2).The adenoma diameters ranged from 9 to 40 mm (mean 22±16 mm) and the carcinoma diameters ranged from 19 to 33 mm (mean 26±6 mm). The 3 adenomas had different echogenicities: One was completely echofree, one was hypoechoic and one isoechoic. The 4 carcinomas however were equally characterized as hypoechoic and echofree. Two of three adenomas and all of the carcinomas showed an incomplete or diffuse margin. Micro-calcifications were found in one adenoma and in every carcinoma. However, no micro-calcifications were observed in cases of benign regressive nodules.Performing shear-wave elastography the adenomas showed lower values than the carcinomas: The tissue velocity of the adenomas ranged from 2.86 m/s to 3.85 m/s (mean 3.32±0.5 m/s) and in carcinomas from 3.89 m/s to 5.66 m/s (mean 4.18±0.3 m/s).Marginal hypervascularization was detected in two adenomas after applying CCDS. One adenoma was hypovascularized. The four carcinomas showed an irregular extreme hypervascularization along their margins as well as an irregular central normo- or hypervascularization in CCDS. The additional HR-Flow helped reducing artefacts.In CEUS the dynamic capillary microvascularization of all carcinomas was very irregular with early enhancement and followed by partial or complete wash-out. In CEUS two adenomas had no wash-out and the other one showed a partial wash-out. CONCLUSION: Using modern multimodal imaging offers new possibilities for the differentiation between benign and malignant thyroid lesions. It is a very important diagnostic tool in addition to the B-Mode TIRADS classification and eases the decision between TIRADS 3, 4 and 5. However, additional multicenter studies are required for more detailed evaluations.

High resolution flow (HR Flow) and Glazing Flow in cases of hepatic flow changes: Comparison to color-coded Doppler sonography (CCDS).

AIM: To evaluate the possibilities of flow detection using high resolution flow (HR Flow) and Glazing Flow technique in patients with liver parenchymal changes and flow changes in comparison to color-coded Doppler sonography (CCDS). MATERIAL AND METHODS: All examinations were performed using a multi frequency matrix convex probe with high resolution technique (SC6-1U/Resona7, Mindray, Shenzhen, China) by one experienced examiner to evaluate the venous, portal venous and arterial liver flow with digital documentation of the dynamic flow parameters like peak systolic flow, end-diastolic flow and resistance index. For liver parenchymal stiffness changes shear wave elastography was performed with at least 10 measurements. By two independent readers an elevation was performed to evaluate the image quality and the degree of flow artefacts, from 0 = not available to 5 points with excellent image quality without flow artefacts. RESULTS: All 40 patients (24 men, 16 women, age 27-83 years, mean 56±5 years) showed morphology changes from B-Mode of the liver parenchyma to inhomogeneous tissue with higher stiffness evaluated by the shear wave elastography (1.45 m/s up to 2.79 m/s±1.79 m/s, considering F1 up to F4 fibrosis) and in 15 cases histopathologically proven liver cirrhosis. In 9 cases after non-acute thrombosis flow reduction of the portal vein was the reason for the diameter less than 5 mm. Flow parameters for the venous flow were between 8 cm/s up to 29 cm/s, mean 14±4 cm/s, for the hepatic portal vein 5 cm/s up to 57 cm/s, mean 17±5 cm/s, for the hepatic artery systolic flow between 50 cm/s up to 127±33 cm/s, end-diastolic flow from 22 cm/s up to 47±8 cm/s. Resistance index for the hepatic artery was between 0.41 up to 0.73, mean 0.67±0.25. The image quality for CCDS over all cases was evaluated for CCDS between 1 up to 4. The mean quality was 2.5±0.5, for HR Flow in combination with Glazing Flow 3±0.5, with significant differences for the 2 readers (P < 0.01). CONCLUSION: Combination of HR Flow with Glazing Flow could be helpful to evaluate morphological und hemodynamic changes of liver arterial flow, portal venous and venous flow. Reduction of flow artefacts in combination with a higher image quality could be helpful for optimizing the digital measurements also for follow up examinations.

Wireless point-of-care ultrasound: First experiences with a new generation handheld device.

AIM: To evaluate the diagnostic reliability of a new generation wireless point-of care ultrasound device for abdominal and thoracic findings. MATERIAL AND METHODS: 40 patients (16 females, 24 males 19 -80 years, on average 56.1 years) were scanned by an experienced examiner using the new wireless Vscan Air device for abdominal and thoracic findings. The probe frequencies were 2-5 MHz (convex probe) and 3-12 MHz for the linear probe. As a reference standard, all patients were also examined using high-end ultrasound (LOGIQ E9/LOGIQ E10). Results were interpreted independently by two examiners in consensus, also with regard to the image quality (0-4, from not assessable = 0, to excellent 4). RESULTS: In all 40 patients (100%) examination with conventional high-end ultrasound and the Vscan Air ultrasound device was feasible. Sensitivity, specificity, positive and negative predictive value for the diagnosis of abdominal and thoracic findings were 63.3%, 100%, 100%, and 40%, respectively. Most main diagnostic findings were detected using the mobile device compared to the high-end ultrasound. Limitations were found regarding characterization and classification of hepatic and renal tumorous lesions.Image quality revealed mostly minor diagnostic limitations for the mobile device, mean 2.9 (SD ± 0.300) and was excellent or with only minor diagnostic limitations for conventional high-end ultrasound, mean 3.25 (SD ± 0.438). CONCLUSION: Due to its easy application and its high diagnostic reliability, point-of-care ultrasound systems of the latest generation represent a valuable imaging method for the primary assessment of abdominal and thoracic findings, especially in patients on intensive care units or in emergency situations.

Predicting the Radiation Sensitivity of Male and Female Rhesus Macaques Using Gene Expression.

Radiosensitivity differs in humans and likely among closely-related primates. Reasons for variation in radiosensitivity are not well known. We examined preirradiation gene expression in peripheral blood among male and female rhesus macaques which did or did not survive (up to 60 days) after whole-body irradiation with 700 cGy (LD66/60). RNA samples originated from a blinded randomized Good Laboratory Practice study in 142 irradiated rhesus macaques. Animals were untreated (placebo), or treated using recombinant human IL-12, G-CSF or combination of the two. We evaluated gene expression in a two-phase study design where phase I was a whole genome screen [next generation sequencing (NGS)] for mRNAs (RNA-seq) using five RNA samples from untreated male and female animals per group of survivor and non-survivor (total n = 20). Differential gene expression (DGE) was defined as a statistically significant and ≥2-fold up- or downregulation of mRNA species and was calculated between groups of survivors and non-survivors (reference) and by gender. Altogether 659 genes were identified, but the overlapping number of differentially expressed genes (DGE) observed in both genders was small (n = 36). Fifty-eight candidate mRNAs were chosen for independent validation in phase II using the remaining samples (n = 122) evaluated with qRT-PCR. Among the 58 candidates, 16 were of significance or borderline significance (t test) by DGE. Univariate and multivariate logistic regression analysis and receiver operating characteristic (ROC) curve analysis further refined and identified the most outstanding validated genes and gene combinations. For untreated male macaques, we identified EPX (P = 0.005, ROC=1.0), IGF2BP1 (P = 0.05, ROC=0.74) and the combination of EPX with SLC22A4 (P = 0.03, ROC=0.85) which appeared most predictive for the clinical outcome for treated and combined (untreated and treated) male macaque groups, respectively. For untreated, treated and both combined female macaque groups the same gene (MBOAT4, P = 0.0004, ROC = 0.81) was most predictive. Based on the probability function of the ROC curves, up to 74% of preirradiation RNA measurements predicted survival with a positive and negative predictive value ranging between 85-100% and associated odds ratios reflecting a 2-3-fold elevated risk for surviving per unit change (cycle threshold value) in gene expression. In conclusion, we identified gender-dependent genes and gene combinations in preirradiation blood samples for survival prediction after irradiation in rhesus macaques.

Contrast enhanced ultrasound (CEUS) with parametric imaging and time intensity curve analysis (TIC) for evaluation of the success of prostate arterial embolization (PAE) in cases of prostate hyperplasia.

AIM: To evaluate the use of dynamic contrast enhanced ultrasound (CEUS) with parametric color-coded imaging and time intensity curve analysis (TIC) for planning and follow-up after prostate arterial embolization (PAE). MATERIAL/METHOD: Before and after selective iliacal embolization by PAE with a follow up of 6 months 18 male patients (43-78 years, mean 63±3.5 years) with histopathological proven benign prostate hyperplasia were examined by one experienced examiner. A multifrequency high resolution probe (1-6 MHz) was used for transabdominal ultrasound and CEUS with bolus injections of 2.4 ml sulphur-hexafluoride microbubbles. Independent evaluation of color-coded parametric imaging before and after PAE by in PACS stored DICOM loops from arterial phase (10-15 s) up to 1min were performed. Criteria for successful treatment were reduction of early arterial enhancement by changes of time to peak (TTP) and area under the curve (AUC) by measurements in 8 regions of interest (ROI) of 5 mm in diameter at the margin and in the center and changes from hyperenhancement in parametric imaging (perfusion evaluation of arterial enhancement over 15 s) from red and yellow to blue and green by partial infarctions. Reference imaging method was the contrast high resolution 3 tesla magnetic resonance tomography (MRI) using 3D vibe sequences before and after PAE and for the follow up after 3 and 6 months. RESULTS: PAE was technically and clinically successful in all 18 patients with less clinical symptoms and reduction of the gland volume. In all cases color-coded CEUS parametric imaging was able to evaluate partial infarction after embolization with changes from red and yellow to green and blue colors in the embolization areas. Relevant changes could be evaluated for TIC-analysis of CEUS with reduced arterial enhancement in the arterial phase and prolonged enhancement of up to 1 min with significant changes (p = 0.0024). The area under the curve (AUC) decreased from 676±255.04 rU (160 rU-1049 rU) before PAE to 370.43±255.19 rU (45 rU-858 rU) after PAE. Time to peak (TTP) did not change significantly (p = 0.6877); TTP before PAE was 25.82±9.04 s (12.3 s-42.5 s) and after PAE 24.43±9.10 s (12-39 s). Prostate volume decreased significantly (p = 0.0045) from 86.93±34.98 ml (30-139 ml) before PAE to 50.57±26.26 ml (19-117 ml) after PAE. There were no major complications and, in most cases (14/18) a volume reduction of the benign prostate hyperplasia occurred. CONCLUSION: Performed by an experienced examiner CEUS with parametric imaging and TIC-analysis is highly useful to further establish prostatic artery embolization (PAE) as a successful minimal invasive treatment of benign prostatic hyperplasia.

Functional ultrasound imaging of the venous valve of the great saphenous vein in the area around the crosse using the novel vector flow technique.

PURPOSE: The aim of our pilot study is to consider if the new flow presentation of the vector flow (V-flow) allows an assessment of the valve morphology of the crosses with respect to an insufficiency. MATERIAL AND METHODS: We performed a total of 50 investigations in which we documented a complete valve closure at the so called "crosse" at the valve of the large saphenous vein, a delayed valve closure or an incomplete valve closure with consecutive insufficiency at the crosse. The valve function of the crosse is crucial for the development of varicosis. For our study we recorded age and gender of the patients. One patient in the study was suffering from Covid19. For the examinations we used a 3-9 MHz probe and a high-end ultrasound device. The examination was performed in a lying position and under quiet conditions. Before examination we practiced inhalation and exhalation as well as "pressing" or coughing with the patients, which resulted in a physiological closure of the venous valves. To rule out thrombosis, we carried out compression sonography on the legs. During the examination we documented the B-scan, the Color-Coded Duplex Sonography, the HR-flow and the V-flow for 3 seconds at the estuary of the crosses and incorporated these parameters into our measurements. Via V-flow, vectors can be imaged by representing the flow of erythrocytes and visually indicate a possible insufficiency due to delayed or incomplete valve closure. RESULTS: 31 of 50 patients (age 19-81years) showed a complete valve closure of the crosses, three of them suffered from thrombosis. In eight of the 50 study participants (age 45-79 years) a delayed valve closure could be diagnosed by V-flow within 1-2 seconds. None of them had a thrombosis, but six of them suffered from cancer. In eleven patients we derived an incomplete valve closure with insufficiency (age 51-88 years). With reflux it took >2 seconds to close the valve. The patient with Covid19 also showed an incomplete valve closure with insufficiency. At the same time this patient showed a Covid19-associated deep vein thrombosis. Eight additional patients also had a thrombosis. Six of them suffered from cancer. Overall, the results were best visualized by V-Flow. CONCLUSION: The crosse as a significant venous structure can be well investigated by V-flow with respect to hemodynamic changes and a resulted reflux. Also associated changes close to the valve can be visualized well.

Contrast-enhanced ultrasound with perfusion analysis in patients with venous malformations before and after percutaneous treatment with ethanol-gel.

INTRODUCTION: Percutaneous sclerotherapy is a well-established treatment option for venous malformations (VM). A recently established sclerosing agent is ethanol-gel. Aim of this study was to identify, if contrast-enhanced ultrasound (CEUS) with an integrated perfusion analysis allows for differentiation between untreated VM, healthy tissue, and with gelified ethanol treated malformation tissue. MATERIAL AND METHODS: In this institutional review board approved prospective study symptomatic VM patients underwent CEUS at exactly the same position before and after sclerotherapy with ethanol-gel. Two experienced sonographers performed all examinations after the bolus injection of microbubbles using a multi-frequency probe with 6 -9 MHz of a high-end ultrasound machine. An integrated perfusion analysis was applied in the center of the VM and in healthy, surrounding tissue. For both regions peak enhancement (peak), time to peak (TTP), area under the curve (AUC), and mean transit time (MTT) were evaluated. Wilcoxon signed rank test was executed; p-values <0.05 were regarded statistically significant. RESULTS: In 23 patients including children (mean age 25.3 years, 19 females) before treatment all identified parameters were significantly higher in the VM center compared to healthy tissue (peak: p < 0.01; TTP: p < 0.01; AUC: p < 0.01; MTT: p < 0.01). Comparing the VM center before and after treatment, TTP (p < 0.02) and MTT (p < 0.01) reduced significantly after sclerotherapy. In surrounding tissue only peak changed after treatment in comparison to pre-treatment results (p = 0.04). Comparing data in the VM center with surrounding tissue after sclerotherapy, results still differed significantly for peak (p < 0.01), TTP (p < 0.01), and AUC (p < 0.01), but assimilated for MTT (p = 0.07). CONCLUSION: All with CEUS identified parameters seem to be excellent tools for differentiating between VM and healthy tissue. TTP and MTT could distinguish between with ethanol-gel sclerotized VM portions and untreated malformation parts and thereby might assist the monitoring of sclerotherapy with ethanol-gel.

Imaging of breast implant and implant-associated complications: Capsular contracture and intra- or extracapsular rupture.

BACKGROUND: In recent years, follow-up after breast reconstruction with silicone implants and the detection of complications have been relieved by the possibility of improved diagnostic methods. METHODS: Between January 2015 and December 2019 a total of 40 patients (29-84 years) with silicone implants were included in this retrospective study. The implants were examined clinically and with modern imaging: general ultrasound imaging (US), magnetic resonance imaging (MRI), high resolution computed tomography (CT) and positron emission tomography -computed tomography (PET-CT). If necessary, a histological/cytological sample was taken. The breast implants were assessed by three radiologists specialized in breast imaging. The grade of capsular contracture was classified according to the Baker classification. RESULTS: All 40 women obtained a clinical examination and an US diagnostic to identify early and more common complications such as implant folding and capsular fibrosis. Depending on the clinical examination and ultrasound findings additional MRI (n = 10), CT (n = 9) and/or PET-CT (n = 2) were performed. 16 patients had implants folding proven with US (n = 16), MRI (n = 6) and CT (n = 1). The grade of capsular fibrosis was determined according to the Baker classification. The following results were obtained in our study: 25 breast implants with Baker grade I and eleven breast implants with Baker grade II, both proven with US; one breast implants with Baker grade III and one breast implant with Baker grade IV, proven with US (n = 2), MRI (n = 1) and CT (n = 1). One patient had intracapsular rupture and one patient had extracapsular rupture, both detected on CT and surgically proven. No patient had a silicone accumulation in the lymph nodes. One patient had pathologically enlarged axillary lymph nodes, which were evaluated as inflammatory changes in PET-CT. Long-term complications such as the development of malignant breast tumors could not be observed. CONCLUSION: To detect early complications after breast implant surgery, a regular clinical examination is indispensable. Imaging methods complement each other and if they are used multimodal, it is easier to identify early complications. Modern diagnostic modalities like ultrasound and magnetic resonance imaging expand the spectrum and improve diagnostic safety.

Contrast enhanced ultrasound (CEUS) to assess pleural pulmonal changes in severe COVID-19 infection: First results.

AIM: Use of contrast enhanced ultrasound (CEUS) in severe cases of COVID-19 infection to assess pulmonary changes near the pleura. MATERIAL AND METHODS: Bedside examinations by an experienced intensive care unit examiner using a multi-frequency probe (C1-6 MHz) with B-mode and CEUS to assess pleural-near changes in severe cases of COVID-19 infection with respiratory failure. CEUS with bolus delivery via a central venous catheter of 2.4 ml Sulphur hexafluoride microbubbles from the arterial phase (10-15 s) to the late phase of 5 min. Digital storage of cine sequences of the lung sound with abdomen for independent assessment with the subsequently performed contrast-enhanced dual-source CT. RESULTS: In 11 intubated and ventilated patients (arithmetic mean 62 years, 48 to 78 years, 3 women) with confirmed severe COVID-19 infections, a peripherally accentuated consolidation with irregular hyperemia was found in the CEUS and also in the CT examination. Of the 5 cases with pulmonary arterial embolisms, signs of right ventricular failure were found. In all cases, using CEUS low perfused areas of the pleura with adjacent hyperemia could be detected, while, with CT segmental contrast medium, gaps with subpleural compressions were found. Interstitial changes near the pleura led to B-lines and to ground glass opacities in the CT. Near the diaphragm a delayed arterial contrast of the liver was observed. In addition, in 2 cases partial atelectasis, in 3 cases marginal pleural effusions were found. CONCLUSION: CEUS opens up new possibilities for bedside monitoring of pleural reactive inflammatory or peripheral thrombus embolism in severe cases of COVID-19 infection.

Contrast enhanced ultrasonography (CEUS) to detect abdominal microcirculatory disorders in severe cases of COVID-19 infection: First experience.

In the hands of experienced examiners, the contrast enhanced sonography (CEUS) offers the possibility to analyze dynamic microcirculatory disturbances in real time dynamically without any risk for kidneys and thyroid gland even in severe progressing disease bedside. Based on severe COVID-19 infections, first experiences with abdominal CEUS examinations are presented. In the stage of an imminent organ failure with significantly reduced kidney and liver function, CEUS can be used to show a narrowing of the organ-supplying arteries, as well as a delayed capillary filling of vessels near the capsule, a regional reduced parenchymal perfusion or an inflammatory hyperemia with capillary hypercirculation. It is possible to quickly rule out organ infarction and to dynamically record the mesenteric arterial and venous blood flow.