Contrast Agent Dose Reduction in MRI Utilizing a Generative Adversarial Network in an Exploratory Animal Study.

OBJECTIVES: The aim of this study is to use virtual contrast enhancement to reduce the amount of hepatobiliary gadolinium-based contrast agent in magnetic resonance imaging with generative adversarial networks (GANs) in a large animal model. METHODS: With 20 healthy Göttingen minipigs, a total of 120 magnetic resonance imaging examinations were performed on 6 different occasions, 50% with reduced (low-dose; 0.005 mmol/kg, gadoxetate) and 50% standard dose (normal-dose; 0.025 mmol/kg). These included arterial, portal venous, venous, and hepatobiliary contrast phases (20 minutes, 30 minutes). Because of incomplete examinations, one animal had to be excluded. Randomly, 3 of 19 animals were selected and withheld for validation (18 examinations). Subsequently, a GAN was trained for image-to-image conversion from low-dose to normal-dose (virtual normal-dose) with the remaining 16 animals (96 examinations). For validation, vascular and parenchymal contrast-to-noise ratio (CNR) was calculated using region of interest measurements of the abdominal aorta, inferior vena cava, portal vein, hepatic parenchyma, and autochthonous back muscles. In parallel, a visual Turing test was performed by presenting the normal-dose and virtual normal-dose data to 3 consultant radiologists, blinded for the type of examination. They had to decide whether they would consider both data sets as consistent in findings and which images were from the normal-dose study. RESULTS: The pooled dynamic phase vascular and parenchymal CNR increased significantly from low-dose to virtual normal-dose (pooled vascular: P < 0.0001, pooled parenchymal: P = 0.0002) and was found to be not significantly different between virtual normal-dose and normal-dose examinations (vascular CNR [mean ± SD]: low-dose 17.6 ± 6.0, virtual normal-dose 41.8 ± 9.7, and normal-dose 48.4 ± 12.2; parenchymal CNR [mean ± SD]: low-dose 20.2 ± 5.9, virtual normal-dose 28.3 ± 6.9, and normal-dose 29.5 ± 7.2). The pooled parenchymal CNR of the hepatobiliary contrast phases revealed a significant increase from the low-dose (22.8 ± 6.2) to the virtual normal-dose (33.2 ± 6.1; P < 0.0001) and normal-dose sequence (37.0 ± 9.1; P < 0.0001). In addition, there was no significant difference between the virtual normal-dose and normal-dose sequence. In the visual Turing test, on the median, the consultant radiologist reported that the sequences of the normal-dose and virtual normal-dose are consistent in findings in 100% of the examinations. Moreover, the consultants were able to identify the normal-dose series as such in a median 54.5% of the cases. CONCLUSIONS: In this feasibility study in healthy Göttingen minipigs, it could be shown that GAN-based virtual contrast enhancement can be used to recreate the image impression of normal-dose imaging in terms of CNR and subjective image similarity in both dynamic and hepatobiliary contrast phases from low-dose data with an 80% reduction in gadolinium-based contrast agent dose. Before clinical implementation, further studies with pathologies are needed to validate whether pathologies are correctly represented by the network.

Radiation dose aspects and establishment of diagnostic reference levels for90Y radioembolisation during angiographic procedure.

90Y radioembolisation (RE) is an angiographic procedure used in patients with both primary and secondary hepatic malignancies. Local tumour control can be achieved by short range tumour irradiation by the regional intra-arterial administration of glass or resin microspheres loaded with 90yttrium that accumulate in the tumorous tissue. The aim of this study was to investigate the radiation exposure of RE and to establish a local diagnostic reference level (DRL). In this retrospective study, dose data from 397 procedures in 306 patients (mean age 67.4 ± 10.6 years, 82 female) who underwent RE between 06/2017 and 01/2022 using one of two different angiography systems were analysed. DRL was set as the 75th percentile of the dose distribution. In the overall population, dose area product (DAP) (median (interquartile range, IQR)) was 26 Gy cm2(IQR 12-50) with a median fluoroscopy time (FT) of 4.5 min (IQR 2.9-8.0). FT and DAP increased significantly with the number of infusion positions (median, IQR): one position 23 Gy cm2(12-46), two positions 33 Gy cm2(14-60), three positions 50 Gy cm2(24-82) (p< 0.0001). Local DRL is 47 Gy cm2for RE and 111 Gy cm2for RE with additional embolisation. Radiation exposure and FT are significantly higher with increasing number of infusion positions as well as additional embolisation. Our established DRLs for RE may serve as a benchmark for dose optimisation.

Contrast Media Reduction in Computed Tomography With Deep Learning Using a Generative Adversarial Network in an Experimental Animal Study.

OBJECTIVE: This feasibility study aimed to use optimized virtual contrast enhancement through generative adversarial networks (GAN) to reduce the dose of iodine-based contrast medium (CM) during abdominal computed tomography (CT) in a large animal model. METHODS: Multiphasic abdominal low-kilovolt CTs (90 kV) with low (low CM, 105 mgl/kg) and normal contrast media doses (normal CM, 350 mgl/kg) were performed with 20 healthy Göttingen minipigs on 3 separate occasions for a total of 120 examinations. These included an early arterial, late arterial, portal venous, and venous contrast phase. One animal had to be excluded because of incomplete examinations. Three of the 19 animals were randomly selected and withheld for validation (18 studies). Subsequently, the GAN was trained for image-to-image conversion from low CM to normal CM (virtual CM) with the remaining 16 animals (96 examinations). For validation, region of interest measurements were performed in the abdominal aorta, inferior vena cava, portal vein, liver parenchyma, and autochthonous back muscles, and the contrast-to-noise ratio (CNR) was calculated. In addition, the normal CM and virtual CM data were presented in a visual Turing test to 3 radiology consultants. On the one hand, they had to decide which images were derived from the normal CM examination. On the other hand, they had to evaluate whether both images are pathological consistent. RESULTS: Average vascular CNR (low CM 6.9 ± 7.0 vs virtual CM 28.7 ± 23.8, P < 0.0001) and parenchymal (low CM 1.5 ± 0.7 vs virtual CM 3.8 ± 2.0, P < 0.0001) CNR increased significantly by GAN-based contrast enhancement in all contrast phases and was not significantly different from normal CM examinations (vascular: virtual CM 28.7 ± 23.8 vs normal CM 34.2 ± 28.8; parenchymal: virtual CM 3.8 ± 2.0 vs normal CM 3.7 ± 2.6). During the visual Turing testing, the radiology consultants reported that images from normal CM and virtual CM were pathologically consistent in median in 96.5% of the examinations. Furthermore, it was possible for the examiners to identify the normal CM data as such in median in 91% of the cases. CONCLUSIONS: In this feasibility study, it could be demonstrated in an experimental setting with healthy Göttingen minipigs that the amount of CM for abdominal CT can be reduced by approximately 70% by GAN-based contrast enhancement with satisfactory image quality.

Evaluation of hearing preservation in adults with a slim perimodiolar electrode.

PURPOSE: Numerous endeavors have been undertaken to preserve hearing in cochlear implant (CI) patients. Particularly, optimization of electrode array design aims at preservation of residual hearing (RH). This study examines whether a slim perimodiolar (PM) electrode array could bear the capability to preserve hearing. METHODS: A total of 47 patients underwent cochlear implantation receiving the PM electrode. (i) Patients with pure tone audiogram (PTA) thresholds better than 85 dB and/or hearing loss for Freiburg speech test numbers less than 60 dB and more than 50% maximum monosyllabic understanding were assigned to the RH group (n = 17), while all others belonged to the noRH group (n = 30). (ii) Another group implanted with a slim straight, lateral wall (LW) electrode was recruited for comparison. RESULTS: We compared 17 RH-30 noRH patients all receiving the PM electrode. RH in PM recipients decreased faster than in LW recipients. No significant differences were observed between both (RH v/s noRH) groups in NRT thresholds, Freiburg speech test and A§E® phonemes. Analogous satisfaction levels were indicated through the questionnaires in terms of sound quality, hearing in silence, noise and directional hearing in both groups. CONCLUSIONS: The results suggest that hearing preservation is influenced not only by electrode shape but various factors. This study opens an avenue for further investigations to elucidate and enumerate the causes for progressive hearing loss.

18F-FDG PET/MR versus MR Alone in Whole-Body Primary Staging and Restaging of Patients with Rectal Cancer: What Is the Benefit of PET?

BACKGROUND: To investigate and compare the diagnostic performance of 18F-Fluorodeoxyglucose (18F-FDG) PET/MR and MR alone in whole-body primary staging and restaging of patients with rectal cancer. METHODS: A retrospective analysis was performed to evaluate diagnostic accuracies of combined reading of PET/MR and MR alone in T, N and M staging against the reference standard. Inter-observer agreement regarding TNM staging was calculated separately for PET/MR and MR alone. RESULTS: A total of 39 studies of 34 patients could be evaluated. Diagnostic accuracies of PET/MR and MR alone were the same in locoregional T staging. For predicting N+ stage, the specificity of combined reading of PET and MR (0.917 and 0.833 for reader 1 and 2, respectively) was slightly higher than MR alone (0.833 and 0.75) without significantly increasing the overall accuracy (0.783 vs. 0.783 and 0.783 vs. 0.739). For detecting distant metastasis, the sensitivities of PET/MR and MR alone were shown equal (1.0 vs. 1.0 and 0.938 vs. 0.938), while the specificity of PET/MR was marginally lower (0.87 vs. 0.913 and 0.826 vs. 0.87). The inter-observer agreements were good to excellent in M (κ = 0.64 and 0.637 for PET/MR and MR alone, p < 0.001) and N staging (0.819 and 0.738, p < 0.001). CONCLUSION: PET did not yield a significant improvement in diagnostic accuracy of PET/MR in TNM staging of rectal cancer, since MR alone facilitated accurate classification of disease stage with good to excellent inter-observer agreement.

DSM-TACE of HCC: Evaluation of Tumor Response in Patients Ineligible for Other Systemic or Loco-Regional Therapies.

PURPOSE: To analyze tumor response, survival and safety in patients with non-resectable hepatocellular carcinoma (HCC) treated with transarterial hepatic chemoembolization using degradable starch microspheres (DSM-TACE) combined with doxorubicin who had no local interventional or systemic therapy alternative according to an interdisciplinary conference. MATERIALS AND METHODS: In this retrospective study, 28 patients (23 male, 5 female, median age 67 years) with unresectable HCC, serum bilirubin levels < 3 mg/dl and contraindications to Sorafenib, RFA, SIRT or cTACE were included. DSM-TACE was performed using Embocept® S (15 ml) and doxorubicin (50 mg/25 ml) three times every 4-6 weeks. Patients were initially staged using the Barcelona Clinic Liver Cancer System (BCLC). Basic liver function was evaluated with the MELD-score. Tumor response was assessed using the modified Response Evaluation Criteria in Solid Tumors (mRECIST). RESULTS: DSM-TACE could be technically successfully performed in all 28 patients. At control imaging after three treatments, the overall rates of complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD) were 14.3 %, 25 %, 39.3 % and 21.4 %, respectively, according to mRECIST. With regard to BCLC stages, the results were as follows (CR, PR, PD): BCLC A (n = 8): 7.1 %, 7.1 %, 10.7 %, 1.2 %; BCLC B (n = 12): 0 %, 10.7 %, 17.9 %, 14.3 %; BCLC C (n = 5): 0 %, 3.6 %, 10.7 %, 3.6 %; BCLC D (n = 3): 3.6 %, 3.6 %, 0 %, 3.6 %. According to this, DSM-TACE showed an overall good median survival of 682 days, although the patients' survival was strictly dependent on BCLC stage. CONCLUSION: DSM-TACE is a safe and promising treatment alternative for patients with unresectable HCC who are ineligible for other loco-regional therapies. KEY POINTS: · DSM-TACE is a safe treatment alternative for patients ineligible for other local or systemic treatments.. · DSM-TACE did not influence the MELD-score in our study population.. · Patients treated with DSM-TACE showed an overall good median survival of 682 days, strictly dependent on BCLC stage.. CITATION FORMAT: · Haubold J, Reinboldt MP, Wetter A et al. DSM-TACE of HCC: Evaluation of Tumor Response in Patients Ineligible for Other Systemic or Loco-Regional Therapies. Fortschr Röntgenstr 2020; 192: 862 - 869.

Anti-inflammatory properties of ursodeoxycholyl lysophosphatidylethanolamide in endotoxin-mediated inflammatory liver injury.

AIM: Endotoxin-mediated liver inflammation is a key component of many acute and chronic liver diseases contributing to liver damage, fibrosis and eventually organ failure. Here, we investigated ursodeoxycholyl lysophosphatidylethanolamide (UDCA-LPE), a synthetic bile acid-phospholipid conjugate regarding its anti-inflammatory and anti-fibrogenic properties. METHODS: Anti-inflammatory properties of UDCA-LPE were evaluated in a mouse model of D-galactosamine/lipopolysaccharide (GalN/LPS)-induced acute liver injury, LPS treated RAW264.7 macrophages and murine primary Kupffer cells. Furthermore, anti-inflammatory and anti-fibrotic effects of UDCA-LPE were studied on primary hepatic stellate cells (HSC) incubated with supernatant from LPS±UDCA-LPE treated RAW264.7 cells. RESULTS: UDCA-LPE ameliorated LPS-induced increase of IL-6, TNF-α, TGF-ß, NOX-2 in the GalN/LPS model by up to 80.2% for IL-6. Similarly, UDCA-LPE markedly decreased the expression of inflammatory cytokines IL-6, TNF-α and TGF-ß as well as the chemokines MCP1 and RANTES in LPS-stimulated RAW 264.7 cells. Anti-inflammatory effects were also observed in primary murine Kupffer cells. Mechanistic evaluation revealed a reversion of LPS-activated pro-inflammatory TLR4 pathway by UDCA-LPE. Moreover, UDCA-LPE inhibited iNOS and NOX-2 expression while activating eNOS via phosphorylation of AKT and pERK1/2 in RAW264.7 cells. HSC treated with conditioned medium from LPS±UDCA-LPE RAW264.7 cells showed lower fibrogenic activation due to less SMAD2/3 phosphorylation, reduced expression of profibrogenic CTGF and reduced pro-inflammatory chemokine expression. CONCLUSION: In the setting of endotoxin-mediated liver inflammation, UDCA-LPE exerts profound anti-inflammatory and anti-fibrotic effect implying a promising potential for the drug candidate as an experimental approach for the treatment of acute and chronic liver diseases.