Significant Dose Reduction for Pediatric Digital Subtraction Angiography Without Impairing Image Quality: Preclinical Study in a Piglet Model

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1 Pediatric Imaging Original Research Racadio et al. Dose Reduction for Pediatric DSA Pediatric Imaging Original Research John Racadio 1 Keith Strauss 2 Todd Abruzzo 1 Manish Patel 1 Kamlesh Kukreja 1 Neil Johnson 1 Mark den Hartog 3 Bart Hoornaert 3 Rami Nachabe 1 Racadio J, Strauss K, Abruzzo T, et al. Keywords: digital subtraction angiography (DSA), dose reduction, image quality, pediatrics DOI:1.2214/AJR Received October 24, 213; accepted without revision December 15, 213. Cincinnati Children s Hospital Medical Center, Department of Radiology, Division of Interventional Radiology has a master research agreement with Philips Healthcare. J. Racadio has had travel expenses paid for Philips Healthcare sponsored symposiums. He has not received any speaking honorariums, is not paid by Philips Healthcare, and does not have any stock options or other financial incentives in Philips Healthcare or any Philips Healthcare products. R. Nachabe, M. den Hartog, and B. Hoornaert are employees of Philips Healthcare. However, the authors who are not Philips Healthcare employees had full control of inclusion of any data and information that might present a conflict of interest for those authors who are Philips Healthcare employees. 1 Department of Radiology, Division of Pediatric Interventional Radiology, Cincinnati Children s Hospital, 3333 Burnet Ave, Cincinnati, OH Address correspondence to J. M. Racadio (john.racadio@cchmc.org). 2 Department of Radiology, Children s Hospital of Cincinnati Hospital, Cincinnati, OH. 3 Interventional X-Ray Department, Philips Healthcare, Best, The Netherlands. AJR 214; 23: X/14/ American Roentgen Ray Society Significant Dose Reduction for Pediatric Digital Subtraction Angiography Without Impairing Image Quality: Preclinical Study in a Piglet Model OBJECTIVE. The purpose of this study was to validate the hypothesis that image quality of digital subtraction angiography (DSA) in pediatrics is not impaired when using a lowdose acquisition protocol. MATERIALS AND METHODS. Three piglets corresponding to common pediatric population sizes were used. DSA was performed in the aorta and renal, hepatic, and superior mesenteric arteries using both the commonly used reference standard and novel radiographic imaging noise reduction technologies to ensure pairwise radiation dose and image quality comparison. The air kerma per frame at the interventional reference point for each DSA acquisition was collected as a radiation dose measure, and image quality was evaluated by five interventional radiologists in a randomized blinded fashion using a 5-point scale. RESULTS. The mean air kerma (± SD) at the interventional reference point with the novel x-ray imaging noise reduction technology was significantly lower (1.1 ±.8 mgy/frame) than with the reference technology (4.2 ± 3. mgy/frame, p =.5). However, image quality was statistically similar, with average scores of 3.2 ±.4 and 3.1 ±.5 for the novel and reference technologies, respectively (p =.934); interrater absolute agreement was.77. CONCLUSION. The DSA radiation dose for pediatrics can be reduced by a factor of four with a novel x-ray imaging noise reduction technology without deterioration of image quality. D igital subtraction angiography (DSA) is used for a wide range of vascular procedures in pediatric patients; however, the radiation dose from DSA is relatively high. In a study using anthropomorphic phantoms, the effective radiation dose delivered to the head of a 5-year-old child from 1 DSA frames was estimated to be equivalent to approximately 1 minute of fluoroscopy [1]. In that same study, the authors showed that in a typical cerebral angiography procedure, the radiation dose from DSA is nearly three times that from fluoroscopy [1]. Pediatric patients are more sensitive to the effects of radiation than adults and have a greater lifetime risk of radiation-induced cancer [2]. As part of the Image Gently public service campaign, an interventional radiology phase, Image Gently, Step Lightly, was instituted to encourage radiation protection during pediatric interventional radiology procedures [3]. Specific radiation dose reduction measures for DSA that were suggested in the campaign included tight collimation to the anatomic area of interest and appropriate choice of the acqui- sition frame rate (number of exposures) to adequately evaluate the vascular anatomy of interest [3]. Although measures such as these can help to reduce radiation dose as much as possible, further reduction is limited using existing x-ray imaging technology. In a recent study [4], 2 adult patients underwent two consecutive cerebral DSA examinations performed first with a standard reference technology and then with a novel noise reduction technology that was associated with a one quarter radiation dose protocol. Paired comparison of the DSA images revealed no significant difference in image quality, while the radiation dose was reduced by a factor of four. However, these data cannot necessarily be extrapolated to the pediatric population because the smaller size of the patients may make relatively small changes in image quality more significant. The data also cannot necessarily be extrapolated to other anatomic regions. Because it would be ethically unacceptable to perform an additional DSA examination on pediatric patients and it would be difficult to define image quality in a phantom from a clinical perspective, we chose to use an 94 AJR:23, October 214

2 animal model to validate the findings of the previous study in pediatric patients. Materials and Methods Three of the authors are employees of Philips Healthcare. However, the authors who are not Philips Healthcare employees had full control of inclusion of any data and information that might present a conflict of interest for those authors who are Philips Healthcare employees. This was a prospective study comparing radiation dose and image quality during DSA acquisitions performed with a reference technology (, Philips Healthcare) and with a novel noise-reduction technology (, Philips Healthcare). DSA was performed using the reference and then the novel technology sequentially on the aorta, renal artery, hepatic artery, and superior mesenteric artery in each of three different pediatric-sized piglets. Imaging Technology This study was performed using a monoplane flat-panel detector C-arm angiographic system (FD2, version 8.1.2, Philips Healthcare). The system was adapted so that both the reference and novel x-ray technique factors could be used along with the corresponding image processing for DSA imaging. The differences in acquisition factors included increased spectral filtration and decreased energy per pulse with the use of, which yielded lower radiation dose. With respect to image processing, enabled noise reduction by performing automatic pixel shifting for motion correction and also used improved spatial and temporal filtering algorithms for noise reduction and image enhancement [4]. Animal Study The animal experiments were performed on piglets following the guidelines of the local institution animal care and use committee. Three piglets weighing 5, 14, and 19.5 kg were used, corresponding to pediatric patients of approximately.5, 3, and 5 years old, respectively [5]. The animals were sedated with an intramuscular injection of xylazine (2 mg/kg), ketamine (2 mg/kg), and buprenorphine (.2 mg/kg) and placed under general anesthesia with % isoflurane administrated by endotracheal tube. An 8-French Skater biliary drainage catheter (InterV) was inserted in the bladder to drain the excreted contrast material. At the end of the experiments, the piglets were euthanized with an IV injection of pentobarbital sodium (1 ml/1 kg). All interventional DSA examinations were performed by the same interventional radiologist. Femoral arterial access was obtained under ultrasound guidance using the Seldinger technique; selective catheterization of each vessel of interest (aorta, renal artery, hepatic artery, and superior mesenteric Dose Reduction for Pediatric DSA TABLE 1: Protocol According to Arterial Site and Piglet Size Piglet Size (kg) artery) was then performed. Flush aortography was performed with a 4-French pigtail catheter (Soft Vu, Angiodynamics), whereas selective arteriography was performed with a 4-French JB-1 catheter (Soft Vu, Angiodynamics) in the two larger piglets and with a 4-French hook catheter (Soft Vu, Angiodynamics) in the smallest piglet. Iodinated contrast material (Optiray 35, Covidien) was injected with a power injector (Mark V Provis, Medrad) using a predetermined contrast volume and injection rate depending on the piglet size and arterial site (Table 1). All injections were performed during anesthesiainduced breath-hold. Before initiating a subsequent arteriography, the contrast material from the venous phase of the preceding angiography was cleared. DSA was performed using a common clinically used pediatric multiphase acquisition consisting of two frames per second (fps) for 3 seconds, followed by 1 fps for 6 seconds and then.5 fps for the remainder of the acquisition. All DSA acquisitions on all animals were performed at the same table height of 13 cm and Arterial Site Aorta Renal Artery Hepatic Artery Superior Mesenteric Artery TABLE 2: FOV Diagonal Lengths According to Arterial Site and Piglet Size Piglet Size (kg) FOV Diagonal Length (cm) Aorta Renal Artery Hepatic Artery Superior Mesenteric Artery source-to-detector distance of 19 cm, resulting in a source-to-skin distance (SSD) of 77.5 cm. However, the FOV and collimation were adapted to each anatomic site and animal size as would be done clinically to ensure optimal visualization of the vessels (Table 2). Each DSA acquisition was performed first with the reference technology and then repeated with the novel x-ray imaging noise reduction technology with the same conditions and settings to ensure a fair pairwise comparison. Examples of such DSA acquisitions with both technologies are shown in Figure 1. All DSA acquisitions were sent to the local hospital research PACS (Merge Healthcare) along with a Radiation Dose Structured Report in which air kerma was reported for each single DSA acquisition. By using a lock-in technique, the air kerma was identical for every frame of a given DSA run. Image Quality Assessment Each DSA acquisition (eight acquisitions in each of the three piglets) underwent blinded evalu- TABLE 3: Five-Point Scoring Scale Used for Image Quality Assessment of Digital Subtraction Angiography (DSA) Acquisitions Score Interpretation of DSA Acquisition (Nondiagnostic) Failing to depict arterial structures in any meaningful way 1 (Poor) Enabling diagnostic evaluation of first-order branches relative to the injected vessel only 2 (Intermediate) Enabling diagnostic evaluation up to second-order branches relative to injected vessel 3 (Good) Enabling diagnostic evaluation up to third-order branches relative to injected vessel 4 (Excellent) Enabling diagnostic evaluation up to vessels beyond third-order branches relative to injected vessel AJR:23, October

3 Racadio et al. ation twice by each of five interventional radiologists, yielding a total of 24 scores. A scoring system (Table 3) based on diagnostic visualization of vessel branches relative to the injected vessel was used to reduce rater subjectivity. The scoring system was based on a previously published scale that was validated on a rabbit model [6]. A similar scale has also been used for image quality assessment of DSA acquisitions performed on adult patients who underwent transarterial chemoembolization of liver metastases [7]. Each DSA acquisition was presented on the same high-resolution clinical three-megapixel ( ) PACS workstation (Model E3cHB, NDS Surgical Imaging) for scoring. Image evaluations were performed without a time limit in a dimly lit reading room with full capability of image manipulation of the complete DSA acquisition, such as frame-byframe or cine display and window-level manipulation, to simulate typical clinical evaluation. The system settings were deidentified so that the radiologists were blinded to the type of technology that was used to generate the acquisitions. Each DSA acquisition was scored twice by each radiologist, with an interval of at least 1 week to avoid memory bias. Data Collection and Statistical Analysis The air kerma for each DSA acquisition and corresponding image quality scores assigned by each reader were tabulated. The institutional medical physicist calibrated the displayed air kerma value at the interventional reference point; the correction factor was 1%. The reported air kerma at the interventional reference point corresponds to the value displayed by the system after calibration. For each DSA image quality assessment, the mean image quality score was used for statistical comparison. Interrater agreement among the five readers was computed using a two-way intraclass correlation coefficient (ICC) for absolute agreement. An ICC below.4, between.41 and.59, between.6 and.74, and.75 or above corresponded with poor, fair, good, and excellent agreement, respectively [8]. The Wilcoxon signed rank test was applied to identify statistical differences in air kerma and image quality between the reference and the novel x-ray imaging noise reduction technology. In addition, a Levene test was applied to the image quality scores to evaluate variation in scores. A value of p <.5 indicated statistical significance. All statistical calculations were performed with commercially available software (Matlab, version R211b, Mathworks). Results The mean (± SD) air kerma at the interventional reference point was significantly reduced from 4.2 ± 3. mgy/frame with the reference technology to 1.1 ±.8 mgy/frame with the novel x-ray technology, yielding a dose reduction of 72.3% (p =.5) (Fig. 2). Fig. 1 Examples of digital subtraction angiography acquisitions performed using reference (left) and novel ) (right) x-ray imaging noise reduction technology (both systems, Philips Healthcare). From top to bottom, injected vessels were aorta, renal artery, hepatic artery, and superior mesenteric artery, respectively. Note difference in background noise between reference and novel technologies; realtime automatic pixel shift of novel technology reduces noise in parenchyma of kidney and liver. The mean image quality scores and their variation were statistically similar between the two technologies, with an average score of 3.2 ±.4 for the novel technology versus 3.1 ±.5 for the reference technology (p =.934 for comparison of mean and p =.912 for comparison of variance) as depicted in Figure 3. Interrater absolute agreement was excellent at.77. Discussion In this study, we evaluated the possibility of reducing the radiation dose (air kerma) for DSA acquisitions without impairing image 96 AJR:23, October 214

4 Dose Reduction for Pediatric DSA Air Kerma (mgy/frame) A Air Kerma (mgy/frame) Fig. 2 Air kerma rate for each digital subtraction angiography (DSA) acquisition. A and B, Wilcoxon plots of air kerma rate for each DSA acquisition show pairwise comparison between reference and novel x-ray technologies (A) (both systems, Philips Healthcare) and corresponding boxplot (B). B Image Quality Score Fig. 3 Graph shows image quality score mean and SD for reference () and novel () x-ray technologies (both systems, Philips Healthcare). quality in a pediatric animal model. DSA has a wide range of uses in pediatric patients, although depending on local expertise and referral patterns, the types of procedures may differ considerably. Some pediatric indications for DSA include renal arteriography for evaluation and treatment of renovascular hypertension [9, 1], hepatic arteriography to evaluate liver transplant vascular pathology [9], superior mesenteric arteriography for diagnosis and treatment of gastrointestinal bleeding (particularly in immunosuppressed patients) [11], bronchial arteriography to evaluate and treat hemoptysis (particularly in cystic fibrosis patients) [12], evaluation and treatment of arteriovenous dialysis grafts, trauma [13], cerebral arteriography for diagnosis and treatment of arteriovenous malformations and aneurysms [14, 15], and evaluation and treatment of vascular malformations [16]. Use of DSA for such complex interventional procedures can expose pediatric patients to relatively high radiation doses. A review of adult patient doses in interventional neuroradiology showed that approximately 66% of the patient exposure during interventional neuroradiologic procedures came from DSA [17]. In a study of adult patients undergoing DSA of the abdominal aorta and lower limbs, it was noted that although DSA accounted for.1% of the procedure time, it contributed more than 88% of the radiation dose [18]. Pediatric institutions are therefore cautious in using DSA because of the importance of minimizing radiation exposure in children. In the previous study that compared the reference technology and novel noise reduction technology in adults undergoing cerebral DSA [4], two consecutive DSA datasets (one using the reference technology and one using the novel technology) were acquired in each patient and reviewed by three neuroradiologists in a randomized blinded fashion. The authors found that a radiation dose reduction of 75% occurred using the novel technology; there was no decrease in image quality in their adult study population. The current study was designed to perform a pairwise comparison with confirmation that there was no significant image quality degradation associated with the same level of dose reduction using the new technology in pediatric patients with smaller vessels. A similar study could not be performed on children for ethical reasons because of their increased sensitivity to radiation-induced cancer [2]; therefore, three different sized piglets that corresponded to pediatric patients at.5, 3, and 5 years old were used. In this piglet model, the use of the noise-reduction algorithm and one quarter dose protocol did not result in any significant decrease in image quality. Such a significant dose reduction to patients will also benefit the interventional radiology staff by reducing their occupational radiation exposure from x- ray scatter. Because the angiography in this study was performed with a power injector and not hand injected, no bias was introduced to image quality due to differences in injection forces. We chose to perform selective angiography on the aorta, renal artery, hepatic artery, and superior mesenteric artery because they are commonly injected arterial vessels in interventional pediatric radiology. Although pediatric cerebral DSA is also commonly performed, it was not performed in this study because, in our experience, the piglet is a poor cerebrovascular model because the thickness of the skull makes visualization difficult. Conclusion The DSA radiation dose for pediatrics can be reduced by a factor of four with the introduction of the novel x-ray technology without deterioration of image quality. References 1. Miksys N, Gordon CL, Thomas K, Connolly BL. Estimating effective dose to pediatric patients undergoing interventional radiology procedures using anthropomorphic phantoms and MOSFET dosimeters. 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