Possible use of digital variance angiography in uterine fibroid embolization: a retrospective observational study.

In this single-center retrospective observational study, 56 patients (mean ± SD age: 44.2 ± 5.3 years) were included who had previously undergone UFE at the Medical Imaging Center, Semmelweis University, Budapest, Hungary, between February 2021 and June 2022. All procedures were conducted in accordance with the 1964 Helsinki Declaration and its later amendments. The study was approved by the Regional Institutional Scientific and Research Ethics Committee, Semmelweis University, Budapest, Hungary (SE RKEB), approval no. 186/2022 on September 26, 2022. Due to the retrospective nature of the study, informed consent was waived. One pre-embolization posteroanterior (PA) pelvic acquisition was included from each patient. Pre-embolization acquisition was preferred as it depicts small arteries and tissue blush of the fibroid, thereby providing a better basis for performance comparison. DSA and DVA images were generated retrospectively from the same unsubtracted acquisition using the GE Advantage Workstation (GE Healthcare, Chicago, Ill., U.S.A.) and the Kinepict Medical Imaging Tool software (Kinepict Ltd., Budapest), respectively. Absolute CNR values and ratios were calculated for each image pair, and visual image quality was assessed by readers in a blinded and randomized manner using a 4-grade Likert scale. All procedures followed institutional protocols. UFE was performed on a GE Innova IGS 5 angiography system by an experienced interventional radiologist with over 20 years of experience. A 4F UF (Cordis, Miami Lakes, FL, U.S.A.) catheter was introduced via right femoral access. Aortography was performed to assess arterial filling of the fibroids. A Medrad Avanta (Bayer AG, Leverkusen, Germany) automated injector was used to inject 20 mL of iodinated contrast media (Ultravist 370, Bayer) at a flow rate of 10 mL/s. A 4F Cobra 1 Glidecath (Terumo, Leuven, Belgium) was positioned in the left uterine artery, followed by the right uterine artery. Hand injections of contrast media (3–6 mL) were performed for the selective angiograms into the uterine arteries. Standard PA pelvic acquisitions (2 fps) were obtained on both sides before and after embolization. DSA runs were saved on the GE workstation, and the unsubtracted files were later used to generate stacked DSA and DVA images as described above. Regions of interest (ROIs) were defined on vessels and background regions using ImageJ (v.2.0.0-rc-68/1.52e, Creative Commons License, NIH). As adjacent regions of blood vessels often contained signals from small arteries or tumor blush, background ROIs were placed outside the fibroid area. Vascular and background ROIs were paired accordingly. The CNR values were calculated for all ROI pairs individually using the following formula [21], where Mean v and Mean b represent the mean pixel intensity values of the vascular and background ROIs, respectively, and Std b is the background SD: CNR = Mean v - Mean b Std b CNRDVA/CNRDSA ratios (R) were also calculated for each corresponding DVA and DSA ROI. Evaluations were conducted by three interventional radiologists with at least 5 years of experience in UFE. The readers were not involved in the treatment of enrolled patients. A randomized, paired evaluation was performed with corresponding DSA and DVA image pairs. The readers were blinded to the imaging modality. The diagnostic value of the acquisitions was compared based on the visibility of large vessels, small vessels, tissue blush (if visible), and the extent of background noise ( Figure 1 ). Diagnostic value was graded using the following 4-grade bidirectional Likert scale: 0. Identical 1. Slightly better/less noise 2. Clear-cut advantage/less noise, no interference with structures 3. Better in every aspect/less noise, no interference, background clear Each image pair was evaluated only once during the survey, and scores were automatically collected in a database for later processing. Radiation dose (total dose-area prod­uct - DAP) and total fluoroscopy time were gathered from the radiation dose information provided for each patient in the “X-ray Radiation Dose Report” of the GE Innova IGS 5 angiography system. Data are presented as median (interquartile range). Calculations of CNR and R medians, along with interquartile ranges (IQR), were performed using Excel 2016 (Microsoft, Redmond, WA). CNR values were compared using the Wilcoxon signed-rank test (Prism 8.4.2, GraphPad). For visual evaluation scores, the mean and standard error of the mean were calculated. Due to the non-Gaussian distribution of the data, the median and IQR were also determined. To assess potential differences between modalities, image pair scores were compared with 0 (equal quality level) using the one-sample Wilcoxon test. Interrater agreement was characterized by Kendall’s W value. The level of significance was set at P < 0.05 for all tests.

Patients (n = 56, mean ± SD age: 44.2 ± 5.3 years) with previously diagnosed uterine fibroids received UFE treatment between February 2021 and June 2022 at the Medical Imaging Center, Semmelweis University, Budapest, and were retrospectively enrolled for image analysis in a consecutive manner. A total of 695 ROI pairs were analyzed from 56 pre-embolization image pairs. The results of the CNR measurements are summarized in Table 1 . The median CNR of DVA images was significantly higher than that of DSA images [29.55 (IQR: 24.96) vs. 16.23 (IQR: 13.24), Wilcoxon signed-rank test, P < 0.001). The R (CNRDVA/CNRDSA) value was 1.96 (IQR: 0.88) ( Figure 2 ). Readers evaluated 56 DSA-DVA image pairs using the 4-grade bidirectional Likert scale, where 0 represented identical image quality. According to the score settings, negative values indicated an advantage for DSA, whereas positive values indicated an advantage for DVA ( Table 2 ). The median (IQR) Likert scores were 0.00 (1.00) for large vessels, −0.33 (1.33) for small vessels, 0.00 (0.67) for tissue blush, and 0.00 (0.75) for background noise ( Figure 3 ). None of these values were significantly different from zero (one-sample Wilcoxon test). Despite moderate interrater agreement levels, ratings were significantly associated with large vessels (W = 0.568, P < 0.001) and small vessels (W = 0.502, P < 0.01). However, agreement was only slight and not significant for tissue blush (W = 0.285, P = 0.766) and background noise (W = 0.349, P = 0.378). Total DAP was 57.0 (21–284) Gy·cm 2 , and total fluoroscopy time was 736 (360–1570) sec.

Our aim was to investigate whether the previously described advantages of DVA can also be observed in UFE intervention. Therefore, we compared the CNR and visual performance of DSA and DVA images in this retrospective observational study. Our results show that DVA provides a significantly higher (about twofold) CNR than DSA, but there is no difference in the visibility of large vessels, small vessels, tissue blush, and background noise. The poor interrater agreement in the latter two categories might reflect that the judgment of tissue blush and background noise is even more subjective. These findings are partly inconsistent with previous observations, as earlier studies demonstrated that DVA was always superior to DSA in both parameters. 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 However, in the present study, angiography conditions were different, as the catheter was in the uterine artery, very close to the target area, ensuring a highly selective injection of contrast media, and the acquisition was performed at a standard radiation level. Under these conditions, DSA provides excellent visual representation, which cannot be outperformed (ceiling effect). Nevertheless, the improved CNR value clearly indicates the quality reserve of DVA. Previous studies have demonstrated that the quality reserve of DVA can be effectively utilized for dose management. A reduction of dose/frame value by 70% provided non-inferior or superior image quality in lower limb interventions compared with full-dose DSA acquisitions. 20 A subsequent randomized controlled trial showed that applying a similar low-dose protocol reduced total DSA-related DAP by 63% and total procedural DAP by 46% without compromising image quality or the diagnostic value of angiograms. 21 The quality reserve of DVA can also be used to reduce contrast media, as DVA provided non-inferior image quality in carotid angiography compared with full-dose DSA when only 50% of the contrast media amount was used. 8 Our preliminary unpublished observation suggests that an 80% reduction in contrast media achieved through dilution still provides excellent image quality in UFE using DVA images, whereas the concomitant DSA images under the same conditions appear poor. Our finding may have important clinical implications if further studies prove the relevance of the increased CNR and increased quality reserve. UFE is a good alternative for the treatment of uterine fibroids, as it presents less burden and less risk for patients than surgical solutions. Nevertheless, this endovascular intervention requires several X-ray angiography acquisitions and repeated injections of iodinated contrast media. These steps carry their own risks, including possible acute and long-term side effects of radiation and potential impairment of kidney function. Obviously, the dose management capabilities, especially the radiation dose reduction ability of DVA, could be very beneficial in UFE, as patients are often of reproductive age. In addition, lower radiation exposure would reduce the risk of radiation-induced occupational hazards for medical staff. The reduction of contrast media usage could also be advantageous by lowering the risk of contrast-induced nephropathy. Our results reveal the potential of DVA for dose management in UFE; nevertheless, further clinical studies are required to validate these claims. Such a study has already been initiated at our center. The radiation dose from our center serves as a baseline for such a study; our data fall well within the range of recent literature [DAP (Gy·cm 2 ; median, range): Nocum et al. 22 : 113.1 (21.9–792); Lacayo et al. 23 : 74.8 (0.32–795); our data: 57 (21–284); total fluoroscopy time (minutes, median, range): Nocum et al. 22 : 11.1 (6.2–33.6); Lacayo et al. 23 : 13.5 (5.7–104); our data: 12.2 (6.0–26.2)]. Our study has some limitations. Due to its retrospective observational nature, the acquisition protocol was predefined and optimized for DSA; therefore, we could not detect any differences in the visual performance of DSA and DVA images. The full validation of DVA in UFE requires prospective clinical trials in which the protocol is appropriately modified to achieve dose management and DVA images are available for the interventional radiologist in real-time in the operating room. 24 In conclusion, our data show that DVA has a substantial quality reserve in uterine artery angiography compared with the traditionally used DSA technology. Although a visual advantage was not observed in the current clinical setting, the twofold CNR of DVA images provides a solid basis for prospective clinical trials, where the dose management capabilities of DVA can be validated in the endovascular treatment of fibroids and adenomyosis. These trials aim to achieve a 70% reduction in dose/frame value while maintaining non-inferior or superior image quality, as already demonstrated in lower limb interventions. Thus, our study indicates that DVA has the potential to reduce the applied radiation dose during UFE for both patients and personnel.