- Email: [email protected]
CT pulmonary angiography using a reduced volume of high-concentration iodinated contrast medium and multiphasic injection to achieve dose reduction
Clinical Radiology 69 (2014) 36e40
Contents lists available at SciVerse ScienceDirect
Clinical Radiology journal homepage: www.clinicalradiologyonline.net
CT pulmonary angiography using a reduced volume of high-concentration iodinated contrast medium and multiphasic injection to achieve dose reduction E.W. Goble, J.A. Abdulkarim* Department of Radiology, George Eliot Hospital NHS Trust, Nuneaton, Warwickshire, UK
article in formation Article history: Received 11 March 2013 Received in revised form 18 July 2013 Accepted 29 July 2013
AIM: To evaluate whether a reduced volume of a higher-concentration iodinated contrast medium delivered with a multiphasic injection could be used in computed tomography pulmonary angiography (CTPA) to achieve a reduction in dose without adversely affecting image quality. MATERIALS AND METHODS: The CTPA images were retrospectively evaluated of 69 patients who received 100 ml of 300 mg iodine/ml ioversol, injected at constant rate of 5 ml/s and 70 patients who received 75 ml of 350 mg iodine/ml ioversol contrast medium delivered using a multiphasic injection protocol (starting at 5 ml/s and reducing exponentially). The degree of opacification in the proximal pulmonary arteries was measured in Hounsfield units. RESULTS: The groups did not differ in terms of age, sex distribution, or weight. The mean iodine dose was lower in the 75 ml of 350 mg iodine/ml group (26.25 versus 29.5 g, p < 0.0001). Mean opacification did not differ significantly between the 75 ml of 350 mg iodine/ml and 100 ml of 300 mg iodine/ml groups in the main pulmonary artery (365 versus 331, p ¼ 0.055) although it was significantly higher in the 75 ml group in the right (352 versus 315, p ¼ 0.024) and left pulmonary arteries (347 versus 312, p ¼ 0.028). Opacification correlated positively with age and negatively with weight (p < 0.001) and when these effects had been accounted for, the differences in opacification were not statistically significant in the main (p ¼ 0.23), right (p ¼ 0.11), or left pulmonary arteries (p ¼ 0.13). The number of suboptimally opacified studies (opacification of less than 250 HU in main pulmonary artery) did not differ between the groups (12 versus 13, p ¼ 0.83). CONCLUSION: A reduction in iodine dose can be achieved without adversely affecting pulmonary arterial enhancement in CTPA by administering a smaller volume of highconcentration contrast medium using a multiphasic injection protocol. Ó 2013 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
Introduction * Guarantor and correspondent: J.A. Abdulkarim, Department of Radiology, George Eliot Hospital NHS Trust, College Street, Nuneaton, Warwickshire CV10 7DJ, UK. Tel.: þ44 2476 351351. E-mail address: [email protected] (J.A. Abdulkarim).
Computed tomography (CT) pulmonary angiography (CTPA) is widely used in the investigation of suspected pulmonary embolism (PE). The technique is recommended by the National Institute for Health and Care Excellence
0009-9260/$ e see front matter Ó 2013 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.crad.2013.07.023
E.W. Goble, J.A. Abdulkarim / Clinical Radiology 69 (2014) 36e40
37
(NICE) as the initial imaging technique in patients with high clinical likelihood of PE and a good-quality negative CTPA obviates the need for further investigation or treatment for PE.1,2 An important aspect of technical quality is the degree of pulmonary arterial opacification, which is related to the rate of iodine administration.3,4 However a balance must be struck as the risk of developing contrast medium-induced nephrotoxicity (CIN) is increased with larger doses of contrast medium.5,6 CIN (more recently referred to as contrast medium-induced acute kidney injury, CI-AKI)7 is a sudden deterioration in renal function following the recent intravascular administration of iodinated contrast medium in the absence of another nephrotoxic event.8 Although usually self-limiting, CIN has been reported to be associated with increased morbidity, mortality, and incidence of non-renal complications.9e11 Therefore, it is desirable to reduce the risk of CIN through contrast medium dose reduction providing this does not adversely affect arterial opacification and compromise CTPA accuracy.12 This is particularly important in patients with pre-existing renal impairment who are at increased risk of developing CIN.9 Advances in CT technology resulting in faster acquisition times have reduced the period for which the pulmonary arteries must be optimally opacified. This has allowed a reduction in the volume and, therefore, dose of contrast medium required in CTPA.13 In animal models and in CT cerebral angiography, a further dose reduction has been achieved by using a reduced volume of a more concentrated contrast medium.3,14 At the George Eliot Hospital NHS Trust, prior to February 2010, the standard technique for performing CTPA was to administer 100 ml of 300 mg iodine/ml contrast medium. On the basis of manufacturer recommendation, there was a change of practice with the introduction of a new technique using a reduced volume of increased-concentration contrast medium (75 ml of 350 mg iodine/ml) delivered by means of “bolus shaping” software. This software reduces the rate of injection throughout the course of the injection. The new technique was felt to have potential patient safety and cost-saving benefits. The aim of the present retrospective study was to investigate whether the new technique resulted in a reduced dose of contrast medium without adversely affecting pulmonary arterial enhancement.
Sixty-nine patients who had undergone CTPA for suspected PE prior to the change in protocol (imaged from September 2009 to February 2010) and 70 patients who had undergone CTPA for suspected pulmonary embolism after the introduction of the new protocol (imaged from October 2010 to January 2011) were identified retrospectively. All CTPA examinations were performed in a single centre.
Materials and methods
Image assessment
The Department of Audit and Research of George Eliot Hospital NHS Trust approved this retrospective study and the need for ethical approval or informed consent was waived.
Retrospective image review was performed by a single reader using a GE picture archiving and communication system (PACS) workstation. Contrast medium opacification was evaluated with ROI radiodensity measurements in the main pulmonary artery, and right and left pulmonary arteries. Contrast medium opacification was considered to be suboptimal if the attenuation measurement in the main pulmonary artery was less than 250 HU. Although there is no agreed standard for minimal contrast medium opacification, a value of 250 HU has been widely used in research literature as a minimal acceptable standard.15,16
Patient selection At George Eliot Hospital NHS Trust a change in CTPA protocol took place in February 2010 following the introduction of a new pump injector and “Optibolus” bolus shaping software (Mallinckrodt Inc., Hazelwood, MO, USA).
CTPA protocol CTPA examinations were performed using a 32 section CT system (Lightspeed, GE Healthcare, Waukesha, WI, USA). Acquisition parameters were as follows: 120 kVp, automatic mA (dose modulated), 800 mA maximum tube current, 0.6 s rotation time, pitch factor 1.375: 1, noise index 28, 1.25 mm slice thickness with 40 mm beam collimation. Standard practice was to use an 18 G cannula placed in the antecubital fossa. The first group received 100 ml of 300 mg iodine/ml ioversol (Optiray 300, Mallinckrodt Pharmaceuticals) delivered at a constant rate of 5 ml/s (total injection time 20 s) using a power injector. The second group received 75 ml of 350 mg iodine/ml ioversol (Optiray 350, Mallinckrodt Pharmaceuticals) delivered via a power injector at an initial rate of 5 ml/s then decreasing exponentially to 4.2 ml/s over the duration of the injection using bolus shaping software (Optibolus, Mallinckrodt Pharmaceuticals) resulting in a total injection time of 16 s. A saline chaser was not used as is practice in our institution. Initiation of the scan was controlled using a bolustracking method, placing a region of interest (ROI) in the main pulmonary artery. The initial low-dose monitoring image took place at 3 s after starting the injection and was repeated every 2 s. The scans were triggered manually when the threshold of 100 HU was achieved in the main pulmonary artery. There followed a delay of 5.5 s for the scan table to move from the monitoring position to the start position during which time the patients were asked to halt their breathing. CTPAs were obtained in a craniocaudal direction with images obtained from the lung apices to the diaphragm. Demographic data including patient age, sex, and weight was either recorded at time of scanning or obtained retrospectively from the patients’ hospital records.
38
E.W. Goble, J.A. Abdulkarim / Clinical Radiology 69 (2014) 36e40
Statistical analysis
Table 2 Number of suboptimal studies in the two groups.
Categorical variables (gender, number of suboptimal scans) were analysed using the chi-square test. Analysis between the two groups to look for differences in age and weight was performed using the ManneWhitney test. The attenuation values of the pulmonary arteries were analysed using an unpaired t-test after showing no evidence of nonnormality with the AndersoneDarling method. The correlation between weight and age with opacification was analysed with Pearson’s correlation coefficient. General linear model analysis of variance (GLM) was performed to investigate the association between demographic variables and differences in attenuation. All statistical tests were conducted at a significance level of p < 0.05. Statistical analyses were performed using Minitab 16 statistical software (Minitab Inc., State College, PA, USA).
Results In the 100 ml of 300 mg iodine/ml group there were 69 patients, 34 male and 35 female with a mean age of 56.7 years (range 19e94 years) and a mean body weight of 85.4 kg (range 44e133 kg). In the 75 ml of 350 mg iodine/ml group there were 70 patients, 29 male and 41 female with a mean age of 60.25 years (range 22e91 years) and a mean body weight of 80.7 kg (range 38.1e117 kg). There was no significant difference between the groups in either age (p ¼ 0.23), sex (p ¼ 0.35), or body weight (p ¼ 0.31). The mean dose of iodine in the 75 ml group was 26.25 g, which was statistically significantly lower than in the 100 ml group where the mean iodine dose was 29.5 g (p < 0.001). The mean attenuation of the main, right, and left pulmonary arteries is shown in Table 1. Although mean opacification in the main pulmonary artery was higher using 75 ml of 350 mg iodine/ml this did not reach statistical significance. In both the left and right pulmonary arteries, however, mean opacification was significantly higher using the low-dose technique. Correlation analysis was conducted to examine the relationship between age, weight, and opacification. Positive correlation was demonstrated between age and opacification in all three vessels. Pearson’s correlation coefficient was 0.41 (p < 0.001) for the pulmonary trunk, 0.46 (p < 0.001) for the right pulmonary artery, and 0.47 (p < 0.001) for the left pulmonary artery. Negative correlation was demonstrated between weight and opacification in all three vessels. Pearson’s correlation coefficient
Group
Number of suboptimal studies (<250 HU in main pulmonary artery)
100 ml of 300 mg iodine/ml 75 ml of 350 mg iodine/ml
13 12 p ¼ 0.83
was 0.39 (p < 0.001) for the main pulmonary artery, 0.38 (p < 0.001) for the right pulmonary artery, and 0.37 (p < 0.001) for the left pulmonary artery. GLM analysis revealed dependence of opacification on weight and age in all three vessels (p < 0.001). The mean difference in opacification between protocols for the main pulmonary artery after adjustment for age and weight was 18.5, which was not statistically significant (p ¼ 0.23). The corresponding differences in opacification between protocols for the right and left pulmonary arteries were 22.7 and 20.3, respectively, which were no longer statistically significant (p ¼ 0.11 right pulmonary artery, p ¼ 0.13 left pulmonary artery). An optimal degree of attenuation was accepted as being 250 HU in the main pulmonary artery. Using this criteria there were 12 suboptimal studies in the 75 ml group compared to 13 suboptimal studies in the 100 ml group, which was not significantly different (p > 0.8; Table 2).
Discussion The present study utilized a smaller volume (75 ml) of a more concentrated contrast medium (350 mg iodine/ml) delivered with bolus-shaping software to bring about a reduction in the patient iodine dose administered during CTPA investigations. There was no significant difference in opacification in the main pulmonary artery between the two protocols. Greater opacification was achieved in the right and left pulmonary arteries, but after adjustment for weight and age the differences in opacification were no longer statistically significant. Therefore, it was concluded that the new technique enabled a lower contrast medium dose to be used with no reduction in mean opacification. Furthermore, there was no difference in the number of suboptimally opacified studies. This has implications for patient safety as a potential means of contributing to a reduced risk of CIN. The incidence of CIN is reported to be low in the general population (less than 2%) but may be as high as 10e40% in those with risk factors, such as diabetes and pre-existing
Table 1 Comparison of attenuation values in the main, right and left pulmonary arteries for the two groups. Radiodensity (HU) SD Arterial segment
100 ml of 300 mg iodine/ml
75 ml of 350 mg iodine/ml
Mean difference (95% confidence interval)
p-Value
Main pulmonary artery Right pulmonary artery Left pulmonary artery
331 83 315 77 312 75
365 118 352 114 347 107
34 (67.8 to 0.7) 38 (70.4 to 5.1) 35 (66 to 3.8)
0.055 0.024 0.028
Values are expressed in Hounsfield units and as mean standard deviation.
E.W. Goble, J.A. Abdulkarim / Clinical Radiology 69 (2014) 36e40
renal impairment.5 Because the risk of CIN is dose-dependent,5,6 it is desirable to use as small an amount of contrast medium as possible. The technique employed in the present study led to a reduction of 11% in iodine dose without compromising the degree of opacification. In addition, the reduced volume of contrast medium used per examination in the new protocol has potential cost-saving benefits; these were calculated to be 20% per CTPA, which is in line with other studies.17 The degree of vascular enhancement during CTPA is related to the amount of iodine delivered into the pulmonary circulation per second.4,18,19,20 The iodine delivery rate is influenced by the injection rate and the concentration of contrast medium with an increase in either of these factors resulting in greater arterial enhancement.4 At a given injection rate, a fixed iodine dose can be delivered into the circulation more quickly using a reduced volume of a more concentrated contrast medium. This increases the iodine delivery rate and achieves a higher peak in arterial enhancement for the same total iodine dose. However, the duration of optimal enhancement is reduced leading to a narrowing of the temporal window for CT imaging.21 The higher peak in arterial enhancement obtained with higher concentration contrast medium has been employed in other studies to enable a smaller volume of contrast medium, and lower iodine dose, to be used.3,14 Fujikawa et al.3 found that a reduced volume of a more concentrated contrast medium (370 mg iodine/ml compared to 300 mg iodine/ml) could be used in CT cerebral angiography to reduce the iodine dose by 1.3% without adversely affecting the degree of opacification. A 26% dose reduction was achieved by using a saline chaser after the bolus of contrast medium, enabling a further reduction in contrast medium volume. Administering the iodine dose in a reduced volume of a more concentrated contrast medium results in a higher peak of arterial enhancement but, as previously stated, this is at the expense of duration of peak enhancement.21 This has the disadvantage of narrowing the temporal window for CT imaging at the desired level of enhancement and requires more precise scan timing. Although a standard delivery rate of 5 ml/s was used in the 100 ml group, bolus-shaping software was used in the 75 ml group with the aim of achieving more prolonged and uniform pulmonary arterial enhancement. This utilized a multiphasic injection where the injection rate decreases exponentially throughout the course of delivery (initial rate 5 ml/s, reducing to 4.2 ml/s, injection duration 16 s). With a uniphasic injection the enhancement increases progressively, peaking shortly after completion of injection, followed by a rapid decline.21 By exponentially decreasing the injection rate, the delivery of contrast medium to the vessels is balanced by the contrast medium clearance from the same compartment, resulting in a steady state in the vessels and more uniform vascular enhancement.22 This makes the timing of the scan less critical. This technique has previously been shown to result in more uniform contrast medium opacification in CT angiography.22 Patient factors have been shown to affect the degree of vascular opacification. Studies have previously shown that
39
body weight adversely affects opacification16,23 and this was replicated in the present study. The effects of age are less clear with some studies having demonstrated no correlation15,16; however, other studies have demonstrated arterial opacification to be positively correlated with age,24,25 and this was demonstrated in the present study. This association has been postulated to be due to decreased cardiac output and blood volume, which may be seen in elderly patients.25 When determining the number of suboptimally opacified studies, 250 HU in the main pulmonary artery was taken as the minimum acceptable opacification. There is no overall consensus as to what radiodensity value constitutes a minimum acceptable level of opacification; figures of 200, 250, and 300 HU have been quoted in previous research studies.15,16,23,24,26 However, 250 HU was felt to be a reasonable figure, which has been used in other, similar studies to define the minimum degree of contrast medium opacification.15,16 Furthermore, it is the authors’ experience, anecdotally, that a single radiodensity measurement in the main pulmonary artery is often recorded whilst reporting CTPAs in clinical practice to determine whether opacification is optimal, the idea being that an embolus could not be confidently excluded if opacification is less than 250 HU. Using this figure to define optimal opacification, the 100 ml and 75 ml protocols in the present study resulted in optimally opacified scans in 81% and 83% of cases, respectively. This compares with 88.9% of scans achieving a value of 250 HU in the main pulmonary artery by Nazaroglu et al.27 although a greater contrast medium dose was employed by those authors (100 ml of 350 mg iodine/ml or 370 mg iodine/ ml). There are various limitations of the present study. Firstly, the data collection was performed retrospectively and not all data were available, such as cannulation details and body weight, for all patients. Those patients for whom a body weight was not recorded at time of the examination or could not be obtained from patient hospital records were excluded from the study. Secondly, although there was a reduction in iodine dose using the new protocol patients were not subjected to follow-up monitoring of renal function, so it was not possible to demonstrate any difference in CIN between the two groups. Furthermore, the reduction in iodine dose was small (11%), and it is not possible to state whether a dose reduction of this magnitude is clinically significant. However, it is prudent to strive for any possible reduction in patient iodine dose provided this does not affect the diagnostic quality of the images obtained. This is particularly true in patients with risk factors for CIN.7 Thirdly, a single examiner measured the ROIs who was not blinded to the contrast medium dose. However, as the analysis was restricted to objective measurement and no attempt was made to give a subjective score of image quality, this was acceptable. Finally, assessment of image quality was restricted to radiodensity measurement of the ROI within the central pulmonary vasculature only, whereas it could be argued that a high degree of opacification is more crucial peripherally to help diagnose or exclude small,
40
E.W. Goble, J.A. Abdulkarim / Clinical Radiology 69 (2014) 36e40
peripheral emboli. However, sampling of small peripheral vessels would be technically difficult and potentially inaccurateda problem that has been alluded to previously in a similar study.16 In summary, the present study demonstrates that in routine clinical practice a reduced volume of contrast material with a higher iodine concentration delivered via a multiphasic injection protocol can be used to deliver a reduced iodine dose. This can be achieved without adversely affecting pulmonary arterial opacification or resulting in an increase in the number of suboptimally opacified studies. This has important implications for patient safety and cost saving.
Acknowledgements
11.
12. 13.
14.
15.
16.
The authors thank Sheena Earl, Adam Ryder, Linda Neale, and the rest of the staff of the Department of Radiology for their invaluable help and advice in completing this study.
17.
References
18.
1. British Thoracic Society Standards of Care Committee Pulmonary Embolism Guideline Development Group. British thoracic society guidelines for the management of suspected acute pulmonary embolism. Thorax 2003;58:470e84. 2. National Institute for Health and Care Excellence. Venous thromboembolic diseases: the management of venous thromboembolic diseases and the role of thrombophilia testing, CG144. London: National Institute for Health and Care Excellence; 2012. 3. Fujikawa A, Tsuchiya K, Imai M, et al. CT angiography covering both cervical and cerebral arteries using high iodine concentration contrast material with dose reduction on a 16 multidetector-row system. Neuroradiology 2010;52:291e5. 4. Fleischmann D. How to design injection protocols for multiple detectorrow CT angiography (MDCTA). Eur Radiol Suppl 2005;15(Suppl. 5):E60e5. 5. Thomsen HS, Morcos SK, Barrett JB. Contrast-induced nephropathy: the wheel has turned 360 degrees. Acta Radiol 2008;49:646e57. 6. Morcos SK, Thomsen HS, Webb JA. Contrast Media Safety Committee of the European Society of Urogenital Radiology (ESUR). Contrast-mediainduced nephrotoxicity: a consensus report. Eur Radiol 1999;9:1602e13. 7. Lewington A, MacTier R, Hoefield R, et al. Prevention of contrast induced acute kidney injury (CI-AKI) in adult patients. Royal College of Radiologist guidelines 2013. Available at: www.rcr.ac.uk/ [accessed 15.03.13]. 8. ACR Committee on Drugs and Contrast Media. ACR Manual on contrast media, v.8. Available at: www.acr.org/Quality-Safety/Resources/ Contrast-Manual. [accessed 11.03.13]. 9. Levy EM, Viscoli CM, Horowitz RI. The effect of acute renal failure on mortalityda cohort analysis. JAMA 1996;275:1489e94. 10. Brown JR, Malenka DJ, DeVries JT, et al. Transient and persistent renal dysfunction are predictors of survival after percutaneous coronary
19. 20.
21. 22.
23.
24.
25.
26.
27.
intervention: insights from the Dartmouth Dynamic Registry. Catheter Cardiovasc Interv 2008;72:347e54. From AM, Batholmai BJ, Williams AW, et al. Mortality associated with nephropathy after radiographic contrast exposure. Mayo Clin Proc 2008;83:1095e100. Ellis JH, Cohan RH. Reducing the risk of contrast-induced nephropathy: a perspective on the controversies. AJR Am J Roentgenol 2009;192:1544e9. Hunsaker AR, Oliva IB, Cai T, et al. Contrast opacification using a reduced volume of iodinated contrast material and low peak kilovoltage in pulmonary CT angiography: objective and subjective evaluation. AJR Am J Roentgenol 2010;195:W118e24. Holalkere NS, Matthes K, Kalva SP, et al. 64-slice multidetector row CT angiography of the abdomen: comparison of low versus high concentration iodinated contrast media in a porcine model. Br J Radiol 2011;84:221e8. Ramadan SU, Kosar P, Sonmez I, et al. Optimisation of contrast medium volume and injection-related factors in CT pulmonary angiography: 64slice CT study. Eur Radiol 2010;20:2100e7. Bae KT, Tao C, Gurel S, et al. Effect of patient weight and scanning duration on contrast enhancement during pulmonary multidetector CT angiography. Radiology 2007;242:582e9. Tsuchiya K, Honya K, Yoshida M, Gomyo M, Nitatori T. Cerebral CT angiography using a reduced dose of contrast material at high iodine concentration in combination with a saline flush. Clin Radiol 2008;63: 1332e5. Radon MR, Kaduthodil MJ, Jagdish J, et al. Potentials and limitations of low-concentration contrast medium (150 mg iodine/ml) in CT pulmonary angiography. Clin Radiol 2011;66:43e9. Fleischmann D. High concentration contrast media in MDCT angiography: principles and rationale. Eur Radiol 2003;13(Suppl. 3):N39e43. Herman S. Computed tomography contrast enhancement principles and the use of high-concentration contrast media. J Comput Assist Tomo 2004;28(Suppl. 1):S7e11. Bae KT. Intravenous contrast medium administration and scan timing at CT: considerations and approaches. Radiology 2010;256:32e61. Bae KT, Tran HQ, Heiken JP. Uniform vascular contrast enhancement and reduced contrast medium volume achieved by using exponentially decelerated contrast material injection method. Radiology 2004;231: 732e6. Schoellnast H, Deutschmann HA, Berghold A, et al. MDCT angiography of the pulmonary arteries: influence of body weight, body mass index, and scan length on arterial enhancement at different iodine flow rates. AJR Am J Roentgenol 2006;187:1074e8. Roggenland D, Peters SA, Lemberg SP, et al. CT angiography in suspected pulmonary embolism: impact of patient characteristics and different venous lines on vessel enhancement and image quality. AJR Am J Roentgenol 2008;190:W351e9. Itoh S, Ikeda M, Satake H, et al. The effect of patient age on contrast enhancement during CT of the pancreatobiliary region. AJR Am J Roentgenol 2006;187:505e10. Lee CH, Goo JM, Lee HJ, et al. Determination of optimal timing window for pulmonary artery MDCT angiography. AJR Am J Roentgenol 2007;188: 313e7. Nazaroglu H, Ozmen CA, Akay HO, et al. 64-MDCT pulmonary angiography and CT venography in the diagnosis of thromboembolic disease. AJR Am J Roentgenol 2009;192:654e61.
Contents lists available at SciVerse ScienceDirect
Clinical Radiology journal homepage: www.clinicalradiologyonline.net
CT pulmonary angiography using a reduced volume of high-concentration iodinated contrast medium and multiphasic injection to achieve dose reduction E.W. Goble, J.A. Abdulkarim* Department of Radiology, George Eliot Hospital NHS Trust, Nuneaton, Warwickshire, UK
article in formation Article history: Received 11 March 2013 Received in revised form 18 July 2013 Accepted 29 July 2013
AIM: To evaluate whether a reduced volume of a higher-concentration iodinated contrast medium delivered with a multiphasic injection could be used in computed tomography pulmonary angiography (CTPA) to achieve a reduction in dose without adversely affecting image quality. MATERIALS AND METHODS: The CTPA images were retrospectively evaluated of 69 patients who received 100 ml of 300 mg iodine/ml ioversol, injected at constant rate of 5 ml/s and 70 patients who received 75 ml of 350 mg iodine/ml ioversol contrast medium delivered using a multiphasic injection protocol (starting at 5 ml/s and reducing exponentially). The degree of opacification in the proximal pulmonary arteries was measured in Hounsfield units. RESULTS: The groups did not differ in terms of age, sex distribution, or weight. The mean iodine dose was lower in the 75 ml of 350 mg iodine/ml group (26.25 versus 29.5 g, p < 0.0001). Mean opacification did not differ significantly between the 75 ml of 350 mg iodine/ml and 100 ml of 300 mg iodine/ml groups in the main pulmonary artery (365 versus 331, p ¼ 0.055) although it was significantly higher in the 75 ml group in the right (352 versus 315, p ¼ 0.024) and left pulmonary arteries (347 versus 312, p ¼ 0.028). Opacification correlated positively with age and negatively with weight (p < 0.001) and when these effects had been accounted for, the differences in opacification were not statistically significant in the main (p ¼ 0.23), right (p ¼ 0.11), or left pulmonary arteries (p ¼ 0.13). The number of suboptimally opacified studies (opacification of less than 250 HU in main pulmonary artery) did not differ between the groups (12 versus 13, p ¼ 0.83). CONCLUSION: A reduction in iodine dose can be achieved without adversely affecting pulmonary arterial enhancement in CTPA by administering a smaller volume of highconcentration contrast medium using a multiphasic injection protocol. Ó 2013 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
Introduction * Guarantor and correspondent: J.A. Abdulkarim, Department of Radiology, George Eliot Hospital NHS Trust, College Street, Nuneaton, Warwickshire CV10 7DJ, UK. Tel.: þ44 2476 351351. E-mail address: [email protected] (J.A. Abdulkarim).
Computed tomography (CT) pulmonary angiography (CTPA) is widely used in the investigation of suspected pulmonary embolism (PE). The technique is recommended by the National Institute for Health and Care Excellence
0009-9260/$ e see front matter Ó 2013 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.crad.2013.07.023
E.W. Goble, J.A. Abdulkarim / Clinical Radiology 69 (2014) 36e40
37
(NICE) as the initial imaging technique in patients with high clinical likelihood of PE and a good-quality negative CTPA obviates the need for further investigation or treatment for PE.1,2 An important aspect of technical quality is the degree of pulmonary arterial opacification, which is related to the rate of iodine administration.3,4 However a balance must be struck as the risk of developing contrast medium-induced nephrotoxicity (CIN) is increased with larger doses of contrast medium.5,6 CIN (more recently referred to as contrast medium-induced acute kidney injury, CI-AKI)7 is a sudden deterioration in renal function following the recent intravascular administration of iodinated contrast medium in the absence of another nephrotoxic event.8 Although usually self-limiting, CIN has been reported to be associated with increased morbidity, mortality, and incidence of non-renal complications.9e11 Therefore, it is desirable to reduce the risk of CIN through contrast medium dose reduction providing this does not adversely affect arterial opacification and compromise CTPA accuracy.12 This is particularly important in patients with pre-existing renal impairment who are at increased risk of developing CIN.9 Advances in CT technology resulting in faster acquisition times have reduced the period for which the pulmonary arteries must be optimally opacified. This has allowed a reduction in the volume and, therefore, dose of contrast medium required in CTPA.13 In animal models and in CT cerebral angiography, a further dose reduction has been achieved by using a reduced volume of a more concentrated contrast medium.3,14 At the George Eliot Hospital NHS Trust, prior to February 2010, the standard technique for performing CTPA was to administer 100 ml of 300 mg iodine/ml contrast medium. On the basis of manufacturer recommendation, there was a change of practice with the introduction of a new technique using a reduced volume of increased-concentration contrast medium (75 ml of 350 mg iodine/ml) delivered by means of “bolus shaping” software. This software reduces the rate of injection throughout the course of the injection. The new technique was felt to have potential patient safety and cost-saving benefits. The aim of the present retrospective study was to investigate whether the new technique resulted in a reduced dose of contrast medium without adversely affecting pulmonary arterial enhancement.
Sixty-nine patients who had undergone CTPA for suspected PE prior to the change in protocol (imaged from September 2009 to February 2010) and 70 patients who had undergone CTPA for suspected pulmonary embolism after the introduction of the new protocol (imaged from October 2010 to January 2011) were identified retrospectively. All CTPA examinations were performed in a single centre.
Materials and methods
Image assessment
The Department of Audit and Research of George Eliot Hospital NHS Trust approved this retrospective study and the need for ethical approval or informed consent was waived.
Retrospective image review was performed by a single reader using a GE picture archiving and communication system (PACS) workstation. Contrast medium opacification was evaluated with ROI radiodensity measurements in the main pulmonary artery, and right and left pulmonary arteries. Contrast medium opacification was considered to be suboptimal if the attenuation measurement in the main pulmonary artery was less than 250 HU. Although there is no agreed standard for minimal contrast medium opacification, a value of 250 HU has been widely used in research literature as a minimal acceptable standard.15,16
Patient selection At George Eliot Hospital NHS Trust a change in CTPA protocol took place in February 2010 following the introduction of a new pump injector and “Optibolus” bolus shaping software (Mallinckrodt Inc., Hazelwood, MO, USA).
CTPA protocol CTPA examinations were performed using a 32 section CT system (Lightspeed, GE Healthcare, Waukesha, WI, USA). Acquisition parameters were as follows: 120 kVp, automatic mA (dose modulated), 800 mA maximum tube current, 0.6 s rotation time, pitch factor 1.375: 1, noise index 28, 1.25 mm slice thickness with 40 mm beam collimation. Standard practice was to use an 18 G cannula placed in the antecubital fossa. The first group received 100 ml of 300 mg iodine/ml ioversol (Optiray 300, Mallinckrodt Pharmaceuticals) delivered at a constant rate of 5 ml/s (total injection time 20 s) using a power injector. The second group received 75 ml of 350 mg iodine/ml ioversol (Optiray 350, Mallinckrodt Pharmaceuticals) delivered via a power injector at an initial rate of 5 ml/s then decreasing exponentially to 4.2 ml/s over the duration of the injection using bolus shaping software (Optibolus, Mallinckrodt Pharmaceuticals) resulting in a total injection time of 16 s. A saline chaser was not used as is practice in our institution. Initiation of the scan was controlled using a bolustracking method, placing a region of interest (ROI) in the main pulmonary artery. The initial low-dose monitoring image took place at 3 s after starting the injection and was repeated every 2 s. The scans were triggered manually when the threshold of 100 HU was achieved in the main pulmonary artery. There followed a delay of 5.5 s for the scan table to move from the monitoring position to the start position during which time the patients were asked to halt their breathing. CTPAs were obtained in a craniocaudal direction with images obtained from the lung apices to the diaphragm. Demographic data including patient age, sex, and weight was either recorded at time of scanning or obtained retrospectively from the patients’ hospital records.
38
E.W. Goble, J.A. Abdulkarim / Clinical Radiology 69 (2014) 36e40
Statistical analysis
Table 2 Number of suboptimal studies in the two groups.
Categorical variables (gender, number of suboptimal scans) were analysed using the chi-square test. Analysis between the two groups to look for differences in age and weight was performed using the ManneWhitney test. The attenuation values of the pulmonary arteries were analysed using an unpaired t-test after showing no evidence of nonnormality with the AndersoneDarling method. The correlation between weight and age with opacification was analysed with Pearson’s correlation coefficient. General linear model analysis of variance (GLM) was performed to investigate the association between demographic variables and differences in attenuation. All statistical tests were conducted at a significance level of p < 0.05. Statistical analyses were performed using Minitab 16 statistical software (Minitab Inc., State College, PA, USA).
Results In the 100 ml of 300 mg iodine/ml group there were 69 patients, 34 male and 35 female with a mean age of 56.7 years (range 19e94 years) and a mean body weight of 85.4 kg (range 44e133 kg). In the 75 ml of 350 mg iodine/ml group there were 70 patients, 29 male and 41 female with a mean age of 60.25 years (range 22e91 years) and a mean body weight of 80.7 kg (range 38.1e117 kg). There was no significant difference between the groups in either age (p ¼ 0.23), sex (p ¼ 0.35), or body weight (p ¼ 0.31). The mean dose of iodine in the 75 ml group was 26.25 g, which was statistically significantly lower than in the 100 ml group where the mean iodine dose was 29.5 g (p < 0.001). The mean attenuation of the main, right, and left pulmonary arteries is shown in Table 1. Although mean opacification in the main pulmonary artery was higher using 75 ml of 350 mg iodine/ml this did not reach statistical significance. In both the left and right pulmonary arteries, however, mean opacification was significantly higher using the low-dose technique. Correlation analysis was conducted to examine the relationship between age, weight, and opacification. Positive correlation was demonstrated between age and opacification in all three vessels. Pearson’s correlation coefficient was 0.41 (p < 0.001) for the pulmonary trunk, 0.46 (p < 0.001) for the right pulmonary artery, and 0.47 (p < 0.001) for the left pulmonary artery. Negative correlation was demonstrated between weight and opacification in all three vessels. Pearson’s correlation coefficient
Group
Number of suboptimal studies (<250 HU in main pulmonary artery)
100 ml of 300 mg iodine/ml 75 ml of 350 mg iodine/ml
13 12 p ¼ 0.83
was 0.39 (p < 0.001) for the main pulmonary artery, 0.38 (p < 0.001) for the right pulmonary artery, and 0.37 (p < 0.001) for the left pulmonary artery. GLM analysis revealed dependence of opacification on weight and age in all three vessels (p < 0.001). The mean difference in opacification between protocols for the main pulmonary artery after adjustment for age and weight was 18.5, which was not statistically significant (p ¼ 0.23). The corresponding differences in opacification between protocols for the right and left pulmonary arteries were 22.7 and 20.3, respectively, which were no longer statistically significant (p ¼ 0.11 right pulmonary artery, p ¼ 0.13 left pulmonary artery). An optimal degree of attenuation was accepted as being 250 HU in the main pulmonary artery. Using this criteria there were 12 suboptimal studies in the 75 ml group compared to 13 suboptimal studies in the 100 ml group, which was not significantly different (p > 0.8; Table 2).
Discussion The present study utilized a smaller volume (75 ml) of a more concentrated contrast medium (350 mg iodine/ml) delivered with bolus-shaping software to bring about a reduction in the patient iodine dose administered during CTPA investigations. There was no significant difference in opacification in the main pulmonary artery between the two protocols. Greater opacification was achieved in the right and left pulmonary arteries, but after adjustment for weight and age the differences in opacification were no longer statistically significant. Therefore, it was concluded that the new technique enabled a lower contrast medium dose to be used with no reduction in mean opacification. Furthermore, there was no difference in the number of suboptimally opacified studies. This has implications for patient safety as a potential means of contributing to a reduced risk of CIN. The incidence of CIN is reported to be low in the general population (less than 2%) but may be as high as 10e40% in those with risk factors, such as diabetes and pre-existing
Table 1 Comparison of attenuation values in the main, right and left pulmonary arteries for the two groups. Radiodensity (HU) SD Arterial segment
100 ml of 300 mg iodine/ml
75 ml of 350 mg iodine/ml
Mean difference (95% confidence interval)
p-Value
Main pulmonary artery Right pulmonary artery Left pulmonary artery
331 83 315 77 312 75
365 118 352 114 347 107
34 (67.8 to 0.7) 38 (70.4 to 5.1) 35 (66 to 3.8)
0.055 0.024 0.028
Values are expressed in Hounsfield units and as mean standard deviation.
E.W. Goble, J.A. Abdulkarim / Clinical Radiology 69 (2014) 36e40
renal impairment.5 Because the risk of CIN is dose-dependent,5,6 it is desirable to use as small an amount of contrast medium as possible. The technique employed in the present study led to a reduction of 11% in iodine dose without compromising the degree of opacification. In addition, the reduced volume of contrast medium used per examination in the new protocol has potential cost-saving benefits; these were calculated to be 20% per CTPA, which is in line with other studies.17 The degree of vascular enhancement during CTPA is related to the amount of iodine delivered into the pulmonary circulation per second.4,18,19,20 The iodine delivery rate is influenced by the injection rate and the concentration of contrast medium with an increase in either of these factors resulting in greater arterial enhancement.4 At a given injection rate, a fixed iodine dose can be delivered into the circulation more quickly using a reduced volume of a more concentrated contrast medium. This increases the iodine delivery rate and achieves a higher peak in arterial enhancement for the same total iodine dose. However, the duration of optimal enhancement is reduced leading to a narrowing of the temporal window for CT imaging.21 The higher peak in arterial enhancement obtained with higher concentration contrast medium has been employed in other studies to enable a smaller volume of contrast medium, and lower iodine dose, to be used.3,14 Fujikawa et al.3 found that a reduced volume of a more concentrated contrast medium (370 mg iodine/ml compared to 300 mg iodine/ml) could be used in CT cerebral angiography to reduce the iodine dose by 1.3% without adversely affecting the degree of opacification. A 26% dose reduction was achieved by using a saline chaser after the bolus of contrast medium, enabling a further reduction in contrast medium volume. Administering the iodine dose in a reduced volume of a more concentrated contrast medium results in a higher peak of arterial enhancement but, as previously stated, this is at the expense of duration of peak enhancement.21 This has the disadvantage of narrowing the temporal window for CT imaging at the desired level of enhancement and requires more precise scan timing. Although a standard delivery rate of 5 ml/s was used in the 100 ml group, bolus-shaping software was used in the 75 ml group with the aim of achieving more prolonged and uniform pulmonary arterial enhancement. This utilized a multiphasic injection where the injection rate decreases exponentially throughout the course of delivery (initial rate 5 ml/s, reducing to 4.2 ml/s, injection duration 16 s). With a uniphasic injection the enhancement increases progressively, peaking shortly after completion of injection, followed by a rapid decline.21 By exponentially decreasing the injection rate, the delivery of contrast medium to the vessels is balanced by the contrast medium clearance from the same compartment, resulting in a steady state in the vessels and more uniform vascular enhancement.22 This makes the timing of the scan less critical. This technique has previously been shown to result in more uniform contrast medium opacification in CT angiography.22 Patient factors have been shown to affect the degree of vascular opacification. Studies have previously shown that
39
body weight adversely affects opacification16,23 and this was replicated in the present study. The effects of age are less clear with some studies having demonstrated no correlation15,16; however, other studies have demonstrated arterial opacification to be positively correlated with age,24,25 and this was demonstrated in the present study. This association has been postulated to be due to decreased cardiac output and blood volume, which may be seen in elderly patients.25 When determining the number of suboptimally opacified studies, 250 HU in the main pulmonary artery was taken as the minimum acceptable opacification. There is no overall consensus as to what radiodensity value constitutes a minimum acceptable level of opacification; figures of 200, 250, and 300 HU have been quoted in previous research studies.15,16,23,24,26 However, 250 HU was felt to be a reasonable figure, which has been used in other, similar studies to define the minimum degree of contrast medium opacification.15,16 Furthermore, it is the authors’ experience, anecdotally, that a single radiodensity measurement in the main pulmonary artery is often recorded whilst reporting CTPAs in clinical practice to determine whether opacification is optimal, the idea being that an embolus could not be confidently excluded if opacification is less than 250 HU. Using this figure to define optimal opacification, the 100 ml and 75 ml protocols in the present study resulted in optimally opacified scans in 81% and 83% of cases, respectively. This compares with 88.9% of scans achieving a value of 250 HU in the main pulmonary artery by Nazaroglu et al.27 although a greater contrast medium dose was employed by those authors (100 ml of 350 mg iodine/ml or 370 mg iodine/ ml). There are various limitations of the present study. Firstly, the data collection was performed retrospectively and not all data were available, such as cannulation details and body weight, for all patients. Those patients for whom a body weight was not recorded at time of the examination or could not be obtained from patient hospital records were excluded from the study. Secondly, although there was a reduction in iodine dose using the new protocol patients were not subjected to follow-up monitoring of renal function, so it was not possible to demonstrate any difference in CIN between the two groups. Furthermore, the reduction in iodine dose was small (11%), and it is not possible to state whether a dose reduction of this magnitude is clinically significant. However, it is prudent to strive for any possible reduction in patient iodine dose provided this does not affect the diagnostic quality of the images obtained. This is particularly true in patients with risk factors for CIN.7 Thirdly, a single examiner measured the ROIs who was not blinded to the contrast medium dose. However, as the analysis was restricted to objective measurement and no attempt was made to give a subjective score of image quality, this was acceptable. Finally, assessment of image quality was restricted to radiodensity measurement of the ROI within the central pulmonary vasculature only, whereas it could be argued that a high degree of opacification is more crucial peripherally to help diagnose or exclude small,
40
E.W. Goble, J.A. Abdulkarim / Clinical Radiology 69 (2014) 36e40
peripheral emboli. However, sampling of small peripheral vessels would be technically difficult and potentially inaccurateda problem that has been alluded to previously in a similar study.16 In summary, the present study demonstrates that in routine clinical practice a reduced volume of contrast material with a higher iodine concentration delivered via a multiphasic injection protocol can be used to deliver a reduced iodine dose. This can be achieved without adversely affecting pulmonary arterial opacification or resulting in an increase in the number of suboptimally opacified studies. This has important implications for patient safety and cost saving.
Acknowledgements
11.
12. 13.
14.
15.
16.
The authors thank Sheena Earl, Adam Ryder, Linda Neale, and the rest of the staff of the Department of Radiology for their invaluable help and advice in completing this study.
17.
References
18.
1. British Thoracic Society Standards of Care Committee Pulmonary Embolism Guideline Development Group. British thoracic society guidelines for the management of suspected acute pulmonary embolism. Thorax 2003;58:470e84. 2. National Institute for Health and Care Excellence. Venous thromboembolic diseases: the management of venous thromboembolic diseases and the role of thrombophilia testing, CG144. London: National Institute for Health and Care Excellence; 2012. 3. Fujikawa A, Tsuchiya K, Imai M, et al. CT angiography covering both cervical and cerebral arteries using high iodine concentration contrast material with dose reduction on a 16 multidetector-row system. Neuroradiology 2010;52:291e5. 4. Fleischmann D. How to design injection protocols for multiple detectorrow CT angiography (MDCTA). Eur Radiol Suppl 2005;15(Suppl. 5):E60e5. 5. Thomsen HS, Morcos SK, Barrett JB. Contrast-induced nephropathy: the wheel has turned 360 degrees. Acta Radiol 2008;49:646e57. 6. Morcos SK, Thomsen HS, Webb JA. Contrast Media Safety Committee of the European Society of Urogenital Radiology (ESUR). Contrast-mediainduced nephrotoxicity: a consensus report. Eur Radiol 1999;9:1602e13. 7. Lewington A, MacTier R, Hoefield R, et al. Prevention of contrast induced acute kidney injury (CI-AKI) in adult patients. Royal College of Radiologist guidelines 2013. Available at: www.rcr.ac.uk/ [accessed 15.03.13]. 8. ACR Committee on Drugs and Contrast Media. ACR Manual on contrast media, v.8. Available at: www.acr.org/Quality-Safety/Resources/ Contrast-Manual. [accessed 11.03.13]. 9. Levy EM, Viscoli CM, Horowitz RI. The effect of acute renal failure on mortalityda cohort analysis. JAMA 1996;275:1489e94. 10. Brown JR, Malenka DJ, DeVries JT, et al. Transient and persistent renal dysfunction are predictors of survival after percutaneous coronary
19. 20.
21. 22.
23.
24.
25.
26.
27.
intervention: insights from the Dartmouth Dynamic Registry. Catheter Cardiovasc Interv 2008;72:347e54. From AM, Batholmai BJ, Williams AW, et al. Mortality associated with nephropathy after radiographic contrast exposure. Mayo Clin Proc 2008;83:1095e100. Ellis JH, Cohan RH. Reducing the risk of contrast-induced nephropathy: a perspective on the controversies. AJR Am J Roentgenol 2009;192:1544e9. Hunsaker AR, Oliva IB, Cai T, et al. Contrast opacification using a reduced volume of iodinated contrast material and low peak kilovoltage in pulmonary CT angiography: objective and subjective evaluation. AJR Am J Roentgenol 2010;195:W118e24. Holalkere NS, Matthes K, Kalva SP, et al. 64-slice multidetector row CT angiography of the abdomen: comparison of low versus high concentration iodinated contrast media in a porcine model. Br J Radiol 2011;84:221e8. Ramadan SU, Kosar P, Sonmez I, et al. Optimisation of contrast medium volume and injection-related factors in CT pulmonary angiography: 64slice CT study. Eur Radiol 2010;20:2100e7. Bae KT, Tao C, Gurel S, et al. Effect of patient weight and scanning duration on contrast enhancement during pulmonary multidetector CT angiography. Radiology 2007;242:582e9. Tsuchiya K, Honya K, Yoshida M, Gomyo M, Nitatori T. Cerebral CT angiography using a reduced dose of contrast material at high iodine concentration in combination with a saline flush. Clin Radiol 2008;63: 1332e5. Radon MR, Kaduthodil MJ, Jagdish J, et al. Potentials and limitations of low-concentration contrast medium (150 mg iodine/ml) in CT pulmonary angiography. Clin Radiol 2011;66:43e9. Fleischmann D. High concentration contrast media in MDCT angiography: principles and rationale. Eur Radiol 2003;13(Suppl. 3):N39e43. Herman S. Computed tomography contrast enhancement principles and the use of high-concentration contrast media. J Comput Assist Tomo 2004;28(Suppl. 1):S7e11. Bae KT. Intravenous contrast medium administration and scan timing at CT: considerations and approaches. Radiology 2010;256:32e61. Bae KT, Tran HQ, Heiken JP. Uniform vascular contrast enhancement and reduced contrast medium volume achieved by using exponentially decelerated contrast material injection method. Radiology 2004;231: 732e6. Schoellnast H, Deutschmann HA, Berghold A, et al. MDCT angiography of the pulmonary arteries: influence of body weight, body mass index, and scan length on arterial enhancement at different iodine flow rates. AJR Am J Roentgenol 2006;187:1074e8. Roggenland D, Peters SA, Lemberg SP, et al. CT angiography in suspected pulmonary embolism: impact of patient characteristics and different venous lines on vessel enhancement and image quality. AJR Am J Roentgenol 2008;190:W351e9. Itoh S, Ikeda M, Satake H, et al. The effect of patient age on contrast enhancement during CT of the pancreatobiliary region. AJR Am J Roentgenol 2006;187:505e10. Lee CH, Goo JM, Lee HJ, et al. Determination of optimal timing window for pulmonary artery MDCT angiography. AJR Am J Roentgenol 2007;188: 313e7. Nazaroglu H, Ozmen CA, Akay HO, et al. 64-MDCT pulmonary angiography and CT venography in the diagnosis of thromboembolic disease. AJR Am J Roentgenol 2009;192:654e61.