With the rapid advancement of CT

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1 Cardiopulmonary Imaging Perspective Weininger et al. Contrast Medium Delivery in Cardiothoracic CT Angiography Cardiopulmonary Imaging Perspective FOCUS ON: Markus Weininger 1 J. Michael Barraza 1 Corey A. Kemper 2 John F. Kalafut 2 Philip Costello 1 U. Joseph Schoepf 1,3 Weininger M, Barraza JM, Kemper CA, Kalafut JF, Costello P, Schoepf UJ Keywords: cardiothoracic imaging, contrast enhancement, coronary arteries, CT angiography, pulmonary arteries DOI: /AJR Received September 7, 2010; accepted after revision October 31, U. J. Schoepf is a consultant for and receives research support from Bayer-Schering, Bracco, GE Healthcare, Medrad, and Siemens Healthcare. J. F. Kalafut and C. A. Kemper are employees of Medrad and Bayer Healthcare. 1 Department of Radiology and Radiological Science, Medical University of South Carolina, Ashley River Tower, 25 Courtenay Dr., Charleston, SC Address correspondence to M. Weininger (weininge@musc.edu). 2 Informatics Research, Medrad, Indianola, PA. 3 Department of Medicine, Division of Cardiology, Medical University of South Carolina, Charleston, SC. WEB This is a Web exclusive article. AJR 2011; 196:W260 W X/11/1963 W260 American Roentgen Ray Society Cardiothoracic CT Angiography: Current Contrast Medium Delivery Strategies OBJECTIVE. Over the last decade, rapid technologic evolution in CT has resulted in improved spatial and temporal resolution and acquisition speed, enabling cardiothoracic CT angiography to become a viable and effective noninvasive alternative in the diagnostic algorithm. These new technologic advances have imposed new challenges for the optimization of contrast medium delivery and image acquisition strategies. CONCLUSION. Thorough understanding of contrast medium dynamics is essential for the design of effective acquisition and injection protocols. This article provides an overview of the fundamentals affecting contrast enhancement, emphasizing the modifications to contrast material delivery protocols required to optimize cardiothoracic CT angiography. With the rapid advancement of CT technology, CT angiography (CTA) has gained widespread clinical use as a noninvasive method to provide an accurate diagnostic assessment of vascular structures and pathophysiology, thus becoming an integral component of modern cardiothoracic imaging [1 13]. However, despite ongoing innovations in scanner technology, protocols for the injection of contrast material often have been kept relatively simple, and as new scanning technology is introduced to clinical practice, the contrast medium injection protocols appropriate for the older generation of CT scanners are often used without critically reviewing their appropriateness or effectiveness. Although individualized contrast injection protocols have found clinical use in some CT studies, such as hepatic imaging, most angiographic CT studies of the thorax either use fixed injection protocols or the volume of contrast medium is adjusted to the estimated acquisition duration. Comparatively few studies have been published on the use of body weight adapted injection protocols for cardiothoracic CTA, focusing on key anatomic structures for thoracic CT contrast enhancement namely the pulmonary artery, thoracic aorta, and cardiac structures, including the coronary arteries [14, 15]. The need for consistent and homogeneous vascular contrast enhancement, which is crucial for a diagnostically accurate and high quality cardiothoracic CTA scan, is often neglected and still remains one of the most challenging aspects of image acquisition. Furthermore, most recent advances in CT, including the introduction of two generations of dual-source CT and wide-area detectors, have dramatically increased the image acquisition speed, effectively rendering obsolete the traditional standardized contrast medium delivery approach for CTA of the coronary arteries, pulmonary arteries, and thoracic aorta. Presently, successful performance of CTA requires much greater adaptability to optimize vascular opacification and improve effectiveness of contrast material delivery. Consequently, basic understanding of vascular contrast dynamics is crucial for the appropriate and individualized design of injection techniques. The purpose of this article is to review basic principles of intravascular contrast injection for cardiothoracic CTA studies and to outline state-of-the-art approaches for individualized scanning protocols. Pharmacokinetics and Physiology of Arterial Contrast Enhancement The magnitude of CTA contrast enhancement depends on several patient-, contrast medium, protocol-, and scanner-related factors, including body weight, cardiac output, scan speed, injection rate, saline flush, and volume, type, and concentration of contrast medium (Fig. 1). The magnitude of arterial enhancement in CTA increases proportionally with W260 AJR:196, March 2011

2 Contrast Medium Delivery in Cardiothoracic CT Angiography PATIENT-RELATED FACTORS Magnitude: Weight, height, cardiac output, age, sex, renal function Timing: Cardiac output and circulation time, venous access Other: Breath-hold, comorbidities CT-RELATED FACTORS Magnitude: Scan duration, scan delay, scan direction Timing: Scan duration, scan delay, scan direction Other: Radiation dose, amount of scan phases the rate of iodine delivery (grams of iodine per second), which corresponds to the product of the contrast medium concentration (milligrams of iodine per milliliter) and the injection rate (milliliters per second). Patient-Related Factors Patient-related factors that most significantly affect contrast enhancement are body size (weight and height) and cardiac output. Less influential factors include age, sex, venous access, renal function, and concomitant comorbidities, as well as various other pathologic conditions [16 20]. A predominant factor affecting the magnitude of vascular contrast enhancement is body weight, which has an inversely proportional relationship to the magnitude of contrast enhancement in a nearly one-to-one ratio [16, 19]. Considering the direct correlation of patient weight to blood volume and extracellular compartment size, larger patients have a larger blood volume in which to dilute the contrast material and therefore require either higher iodine loads or higher delivery rates than do smaller patients to maintain the same degree of arterial enhancement [21]. Several methods have been proposed for calculation of the required contrast material for a given patient s body weight. One simple method implements a 1:1 linear scale, effectively doubling the iodine mass when the patient s body weight doubles [18]. More sophisticated methods have been proposed using parameters such as lean body weight or body surface area [22 24]. The practical drawback to dosing according to these indexes is the added complexity involved in computing them during the image examination because of the need to know the patient s CONTRAST ENHANCEMENT Fig. 1 Overview of different factors involved in contrast enhancement. CONTRAST-RELATED FACTORS Magnitude: Iodine concentration and volume, injection rate, bolus shape, vascular access Timing: Injection rate, injection volume, velocity Other: Injection protocol height in addition to weight. Furthermore, there is limited evidence that dosing by these methods provides more consistent contrast enhancement in CTA compared with dosing by weight alone. The principal patient-related factor affecting the timing of contrast enhancement is the individual s cardiac output [25]. Cardiac output is directly proportional to the contrast bolus arrival time and inversely related to the degree of maximal arterial peak enhancement. When the cardiac output decreases, the circulation of the contrast medium slows, resulting in a delayed contrast bolus arrival, higher peak arterial enhancement, and slower clearance of contrast material from the circulation. Reduced cardiac output results in stronger prolonged contrast enhancement in the vascular territory of interest because of the slow clearance of contrast material. In patients with high cardiac output, the mean contrast enhancement is reduced [25, 26]. Therefore, during cardiothoracic CTA, it is essential to individualize the scan delay for each anatomic region according to each patient s cardiac output by applying test-bolus or bolus-tracking techniques [17, 22]. It is also critical to adjust the contrast volume (or iodine mass) as a function of body weight to account for the impact of cardiac output on the magnitude of contrast enhancement. The chief points regarding patient-related factors are summarized in Appendix 1. CT-Related Factors In addition to the patient, parameters related to the CT scanner itself play a major role in the diagnostically accurate acquisition of contrast-enhanced CT images. Critically important factors include scan duration, scan direction, timing of multiphasic acquisitions, and scan delay in relation to the beginning or completion of contrast material injection. First and foremost, with faster CT scanners and subsequently shorter scan durations, it is essential to know the duration of scan acquisition to tailor the duration of contrast bolus injection as well as to synchronize CT data acquisition with optimal contrast enhancement in the vascular region of interest (ROI) [17]. Information about scan duration is vital for calculation of the injection duration and scan timing, because longer scan durations require an extended contrast agent injection, and shorter scan durations can be acquired with shortened bolus injection durations. For very short scans, however, the injection duration can be decreased only to the extent that the overall enhancement profile is not sacrificed, because contrast medium injected with its duration matched to a short scan duration will likely result in suboptimal contrast enhancement. Contrast-enhanced CT scans are usually performed with the scan direction corresponding to the direction of contrast bolus propagation. This concept applies to angiographic imaging of both the coronary arteries and the thoracic aorta [16]. However, CTA of the pulmonary arteries may benefit from caudocranial scanning. According to Wittram [27], the caudocranial direction is beneficial in pulmonary CTA because most pulmonary emboli are located in the lower lobes, and, if the patient breathes during image acquisition, there is more excursion of the lower lobes than the upper lobes. This is becoming less of a concern with the latest generation of CT scanners and ultrashort acquisition times. In addition to scan duration and direction, exact determination of the contrast material s arrival time is crucial for consistent opacification in patients undergoing CTA. Because of variations in the arterial contrast arrival time in each patient, which is reported to range from 8 seconds to as long as 40 seconds in patients with cardiovascular disease, the scan delay should be individually adjusted according to the vascular territory of interest [17]. The contrast bolus transit time, which is closely associated with each patient s circulation time, can be measured before the diagnostic CT scan and factored into the calculation of scan timing. The individual determination of the transit time or contrast arrival time is typically done using either test-bolus injection or automated bolus-tracking techniques. AJR:196, March 2011 W261

3 Weininger et al. Fig. 2 Typical semiautomated software user interface for individual determination of contrast bolus transit time using test-bolus injection. A C, In this example, region of interest is placed inside target vessels, in this case the pulmonary artery (small circle) and ascending aorta (large circle). D, Resulting enhancement curves display time needed to reach peak of maximum contrast enhancement for test bolus in each vessel. The test-bolus approach is based on the IV injection of a small (~10 20 ml) amount of contrast material during the acquisition of a series of dynamic low-radiation-dose (120 kv, 20 mas) monitoring scans at the level of the vessel of interest (e.g., the ascending aorta for CTA of the coronary arteries and thoracic aorta). An ROI is placed inside the target vessel to generate an enhancement curve, which shows the time needed to reach the peak of maximum enhancement for the test bolus (Fig. 2). Because the measured time to peak enhancement interval determined by the test bolus merely represents the contrast material s arrival time, it should not be simply assumed to serve as the true scan delay but rather as a means of individualizing the scan delay relative to it by including an adequate additional delay before the start of the diagnostic scan [27 31]. The additional delay added to the time to peak should consider the duration of the scan and also the injection duration of the contrast bolus. For the very short scans possible with the latest CT scanners, a longer additional delay is preferable because the longer scan delay ensures that the scan starts closest to maximum contrast opacification. Automated bolus tracking is based on real-time monitoring of the main bolus during injection with the acquisition of a series of dynamic low-dose (120 kv, 20 mas) monitoring scans at the level of the vessel of interest. By placing an ROI, scanning is started manually or automatically once contrast material arrives or after a certain trigger threshold is exceeded [32]. Controversy still exists as to whether testbolus techniques result in actual advantages compared with automated bolus-tracking techniques in terms of optimal vascular attenuation and whether these advantages outweigh the slightly higher overall contrast volume associated with the use of the test-bolus technique. Although some radiologists prefer the bolus-tracking method because of its efficiency and practicality, others continue to use the test-bolus method, particularly for cardiac CTA. The use of a test bolus provides the additional advantage that the patients undergo a test procedure, during which they have the opportunity to practice breath-holding and experience contrast agent infusion before the diagnostic scan. Additionally, a testbolus injection allows mathematic modeling of each patient s cardiovascular and contrast pharmacokinetic response, which can then be used to optimally adjust the diagnostic contrast agent bolus shape [33, 34]. Another key scanning parameter that should be considered when designing contrast agent injection protocols is the applied tube voltage of the x-ray tube. There is a wellknown linear relationship between the attenuation of iodinated contrast media (and the subsequent Hounsfield unit scale) and the energy of the x-rays; as the energy of the x-ray photons approach the K-edge of iodine, the attenuation by the iodine increases. With CTA, the increased attenuation manifests in greater contrast attenuation or image brightness in the contrast medium filled structure. Because the iodinated contrast medium is more efficient at lower tube voltages, it follows that a reduction in volume and flow rate should be possible at the reduced operating voltages. Several authors have reported the ability to reduce contrast dose at reduced tube voltages with thoracic CT [35 38]. Until the recent introduction of iterative reconstruction techniques, a practical limitation for reduced tube voltage CT has been that the increased image noise present at reduced tube voltage examinations could make the image set unusable. However, with the iterative reconstruction algorithms now available in routine clinical use, the tube voltage may be reduced (in certain patients) without affecting the diagnostic quality of the dataset. In these patients, strategies to reduce contrast dose should be entertained as well. A reduction of 20% flow rate and volume may be realized on the basis of initial evidence by Hunsaker et al. [36]. When reducing the tube voltage, attention should be paid to trigger thresholds used with automated bolus-tracking software to avoid scanning too early. For example, with a reduced tube voltage of 80 kv, the contrast attenuation will more quickly pass the threshold set for a 120-kV study. In many W262 AJR:196, March 2011

4 Contrast Medium Delivery in Cardiothoracic CT Angiography cardiothoracic studies, this early triggering will result in scanning while a majority of the contrast bolus is still in the peripheral veins or the superior vena cava. The chief points regarding CT-related factors are summarized in Appendix 1. Contrast Medium Related Factors In addition to patient- and scanner-related factors, key parameters related to the contrast medium also play an important role in achieving adequate contrast enhancement, including vascular access, injection duration, injection rate, bolus shape, and contrast medium volume and concentration. Establishing appropriate vascular access is fundamental to obtaining diagnostically sufficient contrast enhancement. For cardiac CTA, it is preferable to use the right antecubital vein, because dense contrast medium in the brachiocephalic vein has the potential to obscure the supraaortic branches, which can interfere with the appropriate interpretation of arterial coronary artery bypass grafts utilizing the left internal mammary artery. The appropriate injection duration is determined by the scanning conditions and the clinical objectives of the examination. The injection duration is defined as the total contrast material volume divided by the injection rate and has implications for both the peak time and the magnitude of contrast enhancement. Increasing the injection duration, without reducing the injection rate, results in the administration of a larger volume of contrast material into the body, proportionally increasing the magnitude of contrast enhancement. When the injection duration increases, the time for the maximum deposit of contrast medium is delayed, and the time to peak contrast enhancement subsequently increases. A short injection duration (i.e., low contrast volume or high injection rate) results in an earlier arterial peak enhancement and thus requires a short scan delay to maximize contrast enhancement during the scan. Conversely, a longer injection duration (i.e., high volume or low injection rate) results in a later peak enhancement, necessitating a longer scan delay [18, 25, 28, 39 43]. For cardiothoracic CTA, a rapid contrast delivery rate and short injection duration are desirable for optimal arterial enhancement [44]. Choosing the appropriate injection rate is important for achieving homogeneous enhancement and adequate opacification of smaller vessels. If the contrast volume and concentration are kept constant, the injection rate is directly related to maximal enhancement magnitude and inversely related to both bolus arrival time and maximal enhancement duration. When the duration of injection is fixed, a faster injection rate increases the delivery rate and the total amount of contrast medium delivered, resulting in a higher magnitude of vascular enhancement, which is beneficial for arterial CTA applications [16, 25, 45 47]. One limitation of an increased injection rate is the resulting reduction of the temporal window for CT, thus requiring even more precise scan timing. Injection rates of up to 6 ml/s via an antecubital vein are commonly used for CT coronary angiograms, whereas flow rates of 4 ml/s are reported for pulmonary CTA [14, 27, 48 53]. However, injection rates greater than 8 ml/s do not appear to increase contrast enhancement because of the reflux of contrast agent into the inferior vena cava and hepatic veins, even in patients without right heart failure [54]. Adequate shaping of the injection bolus supports achievement of the desired enhancement pattern while minimizing artifacts, which otherwise could limit diagnostic quality (Fig. 3). Before the introduction of double-headed dual-syringe power injectors, the routine administration of contrast material consisted of a single uniphasic bolus of pure and undiluted contrast material. With this uniphasic injection method, the time enhancement response progressively increases and peaks shortly after the completion of the injection, followed by a rapid decline in enhancement. This enhancement pattern, which lacks a true plateau of peak enhancement, is referred to as a hump or peaked enhancement [16]. With CTA scan times of up to seconds using single-, dual-, and 4-slice CT, image acquisition often occurred during the injection of contrast material and ended while the brachiocephalic veins were still filled with contrast material, leading to streak and beam-hardening artifacts [28, 55, 56]. A common approach to preventing artifacts with earlier generation scanners was adding an extended delay until the contrast material was finished injecting, often at the expense of missing the peak of contrast enhancement. Furthermore, the injection rate of contrast agent with CTA is typically greater than the endogenous flow rate of blood Fig year-old man with acute chest pain. A and B, Multiplanar reformats of coronary CT angiography reveal streak artifacts caused by dense contrast media in superior vena cava (arrow, A), which severely limits diagnostic quality of proximal right coronary artery (arrowheads). C, In 3D volume-rendering view, streak artifacts (arrow) mimic stenosis. Fig. 4 Comparison of different contrast media injection protocols. A, Image illustrates contrast-enhanced coronary CT angiography (CTA) using monophasic injection protocol. Severe streak artifacts (arrows) generated by inflow of high contrast density from superior vena cava limit delineation of right atrium and diagnostic accessibility of proximal right coronary artery. B, Image illustrates contrast-enhanced coronary CTA using biphasic contrast bolus. High and homogeneous contrast attenuation can be seen in left heart. However, low attenuation of chambers of right heart severely decreases visualization of septum and tricuspid valve structures. C, Contrast-enhanced coronary CTA using triphasic injection protocol, allowing high and homogeneous contrast enhancement of left atrium and left ventricle, clearly depicts mitral valve apparatus. Image shows diagnostically sufficient enhancement of right atrium and right ventricle with absence of any streak artifacts. AJR:196, March 2011 W263

5 Weininger et al. draining through the peripheral veins. Upon termination of the contrast injection, the column of contrast agent in the peripheral veins slows to the endogenous flow rate in the vessels, potentially leading to an excessive broadening of the contrast material bolus. With the availability of dual-syringe power injectors, biphasic injection protocols have been introduced. Biphasic injection protocols typically consist of injection of contrast material followed by a saline bolus, usually injected at the same flow rate as the contrast material. The rationale behind the introduction of this saline chaser or flush immediately after the contrast media was to alleviate the problems encountered with monophasic injection Enhancement (HU) Enhancement (HU) mg l/ml 320 mg l/ml 370 mg l/ml Time (s) A 80 ml 100 ml 120 ml Time (s) C Enhancement (HU) protocols [30, 57 61]. According to a study by Yamaguchi et al. [62], at least 18 ml of saline flush, injected at the same flow rate of the contrast bolus, is needed to ensure a tight bolus of contrast material into the central circulation and allows the reduction of streak and beam-hardening artifacts provoked by contrast material in peripheral veins or the right atrium and ventricle of the heart, respectively [16]. An additional benefit is a more economical use of contrast by recruiting contrast material for vascular enhancement that would otherwise not be used [63, 64]. A slight modification of this biphasic protocol (one injection of undiluted contrast material followed by an undiluted saline chaser) is a biphasicconcentration protocol. A biphasic-concentration protocol utilizes two boluses, each consisting of a different contrast concentration (an initial undiluted contrast bolus followed by a diluted contrast bolus), which improves right ventricular enhancement and reduces artifacts from undiluted contrast material in the superior vena cava. A thoughtful use of a saline chaser in a biphasic protocol results in contrast enhancement without streak artifacts. However, a limitation of this technique in cardiac CT is that the right ventricle may be completely unenhanced, limiting the visualization of the ventricular septum or pathologic abnormalities, such as thromboembolisms or tumors. T Peak = 25 s T Peak = 28 s T Peak = 32 s 4 ml/s 5 ml/s 6 ml/s Time (s) B Fig. 5 Simulation of different time enhancement curves in 40-year-old, 75 kg, 6-foot-tall man using Bae-Heiken-Brink [25] full-body contrast pharmacokinetic model. A, Graph shows relationship between contrast enhancement and concentration of contrast material. Contrast volume and flow rate were held constant (80 ml at 5 ml/s) but concentration was varied at 300, 320, and 370 mg I/mL. B, Injection of three different flow rates (100 ml volume) of 370 mg I/mL contrast material and predicted enhancement in thoracic aorta were simulated. For higher flow rates (and shorter injection duration), peak of enhancement occurs sooner than with lower flow rates. C, Graph outlines simulation of same patient with three different volumes of contrast material injected. W264 AJR:196, March 2011

6 Contrast Medium Delivery in Cardiothoracic CT Angiography TABLE 1: Overview of Key Contrast Enhancement Variables for Selected Cardiothoracic CT Angiography Protocols Flow Rate Volume Scan Timing Contrast Agent Concentration Test Bolus Bolus Triggering Fixed (mg I/mL) Fixed Weight Based Dilution Phase Optional (10%) Fixed or Examination Based Indication, Examination Not recommended 320, 350, 370, 400 b 4 5 ml/s > 120 kg, 5 ml/s; 120 kg, 4.5 ml/s (Scan duration + 3 s) flow rate (minimum 70 ml) ROI in pulmonary artery; threshold, 180 HU (80 kv use 250 HU) Pulmonary Time to peak arteries a plus 3 s Coronary arteries a Optional (30%) Not recommended 320, 350, 370, 400 b 5 6 ml/s > 120 kg, 5 ml/s; 120 kg, 4.5 ml/s (Scan duration + 2 s) flow rate (minimum 50 ml) ROI in ascending aorta; threshold, 120 HU (80 kv use 200 HU) CT angiography Time to peak plus 2 s Optional (20%) Not recommended 320, 350, 370, 400 b 5 ml/s > 120 kg, 5 ml/s; 120 kg, 4.5 ml/s (Scan duration + 2 s) flow rate (minimum 70 ml) ROI in descending aorta; threshold, 120 HU (80 kv use 200 HU) Time to peak plus 3 s Coronary artery bypass graft Optional (20%) Not recommended 320, 350, 370, 400 b 5 ml/s > 120 kg, 5 ml/s; 120 kg, 4.5 ml/s (Scan duration + 2 s) flow rate (minimum 80 ml) ROI in descending aorta; threshold, 120 HU (80 kv use 200 HU) Function Time to peak plus 3 s Optional (20%) Not recommended 320, 350, 370, 400 b 5 ml/s > 120 kg, 5 ml/s; 120 kg, 4.5 ml/s (Scan duration + 2 s) flow rate (minimum 50 ml) ROI in left ventricle; threshold, 120 HU (80 kv use 200 HU) Pulmonary veins a Time to peak plus 2 s Optional (10%) 320, 350, 370, 400 b 4 5 ml/s > 120 kg, 5 ml/s; 120 kg, 4.5 ml/s (Scan duration + 4 s) flow rate (minimum 80 ml) 20 s after administration of contrast agent ROI in descending aorta; threshold, 140 HU (80 kv use 200 HU) Thoracic aorta a Time to peak plus 4 s Optional (10%) 320, 350, 370, 400 b 4 5 ml/s > 120 kg, 5 ml/s; 120 kg, 4.5 ml/s (Scan duration + 5 s) flow rate (minimum 90 ml) 20 s after administration of contrast agent ROI in descending aorta; threshold, 140 HU (80 kv use 200 HU) Time to peak plus 4 s Thoracic aorta with aneurysm Note ROI = region of interest. a Also consider the use of commercially available contrast protocol generation software. b Not commercially available in the United States. As reported in the literature, a triphasic contrast protocol can overcome the challenge of reduced right-heart opacification [30, 57, 58, 65] (Fig. 4). Triphasic protocols typically consist of three distinct contrast phases: a contrast material only phase, followed by a contrast material or saline mixture injected at the same rate of the first phase, and completed by a saline flush phase as the third component. To achieve the mixed middle phase, a power injector capable of simultaneous contrast agent and saline injection is required. The middle phase, though, can also consist of a small volume of contrast agent injected at a lower rate than the first phase. However, a theoretic disadvantage of reducing the flow rate between phases is that the contrast column loses momentum, which may result in timing deficiencies or a very broad enhancement profile. According to the literature, applying a triphasic protocol consisting of a 50-mL 70% saline and 30% contrast medium mixture and 30 ml of saline, all injected at 6 ml/s, improved the visualization of right heart structures while maintaining left heart image quality, including coronary arteries [65]. To further refine contrast injection, Bae et al. [66, 67] investigated multiphasic injection schemes using a computer-based compartmental model of the cardiovascular system. They concluded that uniform prolonged vascular enhancement could be achieved by applying a multiphasic protocol with an exponentially decelerating injection. It is worth noting that the validation studies testing these exponentially decelerated injections were performed on 4- and 16-MDCT scanners on which the typical scan durations for thoracic CTA examinations were seconds. It is uncertain whether CTA examinations performed with contemporary scan acquisitions would benefit from these methods because the goal for optimal enhancement is less achieving uniform enhancement over an extended scan duration but rather coordinating scan acquisition at the peak of contrast enhancement in the vessel. Because the degree of vascular enhancement over time is proportional to the amount of iodine administered, the concentration of contrast medium is another essential variable in achieving optimal enhancement. When contrast volume, injection rate, and scan parameters (kilovoltage and tube current) are kept constant, a significantly higher attenuation of the vessels can be reached by using contrast agents with high iodine concentrations, which is desirable for arterial cardiotho- AJR:196, March 2011 W265

7 Weininger et al. racic CTA [68]. Clinically, the iodine delivery rate can be adjusted by either changing the iodine concentration of the contrast material or modifying the injection rate. Furthermore, the same degree of vascular enhancement can be obtained with contrast agents with low iodine concentrations by increasing the injection flow rate. Because high iodine administration rates (1.6 2 g I/s) are optimal for arterial enhancement of HU, the routine use of contrast agents with high iodine concentrations (i.e., 350, 370, or 400 mg I/mL) allows the injection rate to be decreased, thus minimizing the risk of contrast extravasation. However, to prevent perivenous streak artifacts at the level of the brachiocephalic veins, agents with high iodine concentrations are not recommended if a uniphasic injection is applied [68, 69]. Furthermore, the increased viscosity of agents with high iodine concentrations requires warming of contrast material before administration. Constant efforts are made to further individualize contrast administration to each patient. The work of Bae et al. [25, 66, 67], Fleischmann [70], and Fleischmann and Hittmair [71] show the feasibility and benefit of individually customized contrast protocols based on additional factors beyond weight, including procedure information, patient characteristics, and data from test-bolus injections, allowing individualization of scan delay computation. With knowledge of scan delay and scan duration, further refinements and customizations of the contrast protocol are possible. Numeric simulations based on the Bae-Heiken-Brink [25] fullbody pharmacokinetic model were used to refine the relationship between the rate of iodine administration and patient weight (Fig. 5). Furthermore, Fleischmann and Hittmair [71] developed a novel mathematic approach for designing injection protocols based on the detailed analysis and sophisticated manipulation of test bolus data with the ability to further reduce individual enhancement variability. More advanced individualized contrast protocols that use test-bolus data derived from multiple ROIs in the cardiopulmonary anatomy are in development, allowing the radiologist to prospectively choose a contrast enhancement target in the vascular territory of interest while attempting to deliver a minimally sufficient dose of contrast material to the patient [72]. Although the principles of contrast protocol design are thoroughly investigated in the literature, a practical challenge remains how to translate these findings into clinical routine for application in everyday patient care. To date, the routine individualization of sophisticated contrast protocols at the point of care remains a challenge for technologists. However, with further integration and enhanced connectivity between the power injector and the imaging technique, these advanced algorithms may become more robust and easier to apply in routine clinical settings, potentially enhancing a technologist s workflow and enabling accurate contrast delivery data collection. With respect to overall image quality, advanced integration furthermore has the potential to allow the implementation of contrast protocol design and delivery strategies envisioned by Bae et al. [25], Fleischmann and Hittmair [71], and Mahnken et al. [73]. An additional means to facilitate routine application of sophisticated injection algorithms has been the recent introduction of commercial software solutions that enable the individual computation of patient- and procedure-specific protocols directly at the point of care in the CT suite [74]. Software algorithms customize the injection protocol using patient weight, scan duration, contrast material concentration, and attributes of a timing bolus scan, adapting the iodine delivery rate (grams of iodine per second) according to a nonlinear relationship among these factors. According to a study published by Seifarth et al. [74], the individualized construction of the contrast injection protocol according to patient-specific parameters and contrast dynamics determined by a test bolus leads not only to a more homogeneous attenuation of the coronary arteries at coronary CTA but also to a smaller impact of the patient s body mass index on coronary opacification compared with that seen with standard injection protocols. With individualized contrast protocol technology, the potential exists to minimize the frequency of subdiagnostic scans in cardiothoracic CTA Fig. 6 Examples of high-quality contrast-enhanced coronary CT angiography studies necessary to reliably exclude coronary artery stenosis. A C, Curved multiplanar reformations of right coronary artery display strong homogeneous contrast enhancement of all vascular segments. D F, Images from 3D volume-rendering technique provide additional high-quality anatomic overview. W266 AJR:196, March 2011

8 Contrast Medium Delivery in Cardiothoracic CT Angiography studies due to poor contrast delivery and scan synchronization [75]. Several studies investigating contrast enhancement of CT pulmonary angiography discovered that up to 40% of indeterminate CT pulmonary angiograms were attributable to poor contrast bolus enhancement [76 80]. For these reasons, software integrated into the clinical workflow holds promise to reduce the variation in contrast agent delivery across patients, indications, and clinicians while ensuring adequate opacification, thereby leading to enhanced patient care. The chief points regarding contrast material related factors are summarized in Appendix 1. Clinical Considerations With cardiothoracic CTA, the key anatomic structures to be considered are the thoracic aorta, including cardiac structures, and the pulmonary artery. Thus, imaging protocols should be designed to facilitate optimal contrast enhancement of these structures (Table 1). Aorta and Coronary Arteries Continuous advances in CT technology currently allow second and subsecond acquisitions of high-resolution motion-free images of the heart and coronary arteries within one single breath-hold and high diagnostic accuracy [3, 81 83] (Fig. 6). According to the literature, attenuation of HU for the thoracic aorta and HU for the coronary arteries can be considered diagnostically sufficient enhancement with moderngeneration scanners [16, 39, 84 87]. A wide range of contrast material administration and scanning protocols has been proposed, grouping the thoracic aorta and coronary arteries together because of their circulatory proximity, applying contrast volumes of ml and injection rates of 3 8 ml/s [33, 50, 68, 69, Fig. 7 Contrast-enhanced pulmonary CT angiography. A, Image illustrates ill-timed contrast bolus with resulting washout of main pulmonary arteries and subsequent contrast enhancement of less than 300 HU. In this example, pulmonary veins have higher magnitude of enhancement than pulmonary arteries do. B, Image illustrates application of individualized contrast protocol leading to bright homogeneous enhancement of main pulmonary arteries (400 HU) and segmental and subsegmental arteries ]. Because scan durations have continuously been shortened with newer-generation scanners, the literature has tended to favor application of smaller contrast volumes for average-sized adult patients with invariable use of saline chasers [16, 97 99]. In addition, the newest CT scanners are expected to further reduce the required amount of contrast material to a mere physiologic minimum, with the effect of the scan duration itself becoming insignificant in the determination of iodine dose, making a precise coordination between scan time and contrast administration crucial for adequate contrast enhancement [16, 100]. To achieve optimal levels of contrast enhancement, it is recommended to individually adjust the required iodine dose and injection duration according to the body size, iodine delivery rate, injection duration, and CT scan speed [16, 17]. Different calculation schemes have been proposed to estimate the individual amount of contrast medium and injection rate required to achieve diagnostically satisfactory contrast enhancement in the aorta and coronary arteries [15, 16, 22, 101]. In addition, several calculation algorithms have been outlined to determine optimal scan delay con- Fig. 8 Contrast-enhanced pulmonary CT angiography. A, Image shows ill-timed contrast administration resulting in poor overall contrast enhancement; however, emboli (arrows) in right main pulmonary artery and left lower lobe pulmonary artery can still be depicted. B, In comparison, well-timed opacification is seen, leading to bright and homogeneous enhancement of pulmonary arteries and thoracic aorta with clear delineation of massive emboli (arrows) in both main pulmonary arteries involving all lobar arteries. C, Corresponding 3D volume-rendering image of same patient illustrates resulting reduced quantity of perfused pulmonary arteries. AJR:196, March 2011 W267

9 Weininger et al. Fig. 10 Emerging CT applications. A D, Myocardial perfusion imaging (A and B) and myocardial viability imaging (C and D) often need to depict the slightest changes in myocardial iodine concentrations (arrows, B D). Therefore, consistent and exact contrast delivery is crucial. Fig. 9 Contrast-enhanced CT angiography of thoracic aorta. A C, Images illustrate incorrect coordination between contrast bolus arrival and scan delay, resulting in contrast washout and heterogeneous contrast enhancement of thoracic aorta (arrow). D F, In comparison, appropriate synchronization of relevant variables, leading to homogeneous enhancement, as illustrated in curved multiplanar reformation of thoracic aorta (D) and corresponding 3D volume-rendering images (E and F). sidering the key factors of contrast medium injection duration, contrast arrival time, and scan duration [16, 22, 25, 102]. Besides the optimization of contrast enhancement magnitude and scan timing, minimizing contrast medium related artifacts is crucial. In addition to individualization of contrast protocols according to patient-related factors, several studies suggest the integration of spilt bolus approaches to further reduce the risk streak artifacts [30, 57 59, 65]. Pulmonary Arteries Pulmonary CTA has become firmly established as the new reference standard for the diagnosis of pulmonary embolism and has mostly replaced scintigraphic studies and conventional pulmonary angiography [ ]. Because exact timing of the contrast bolus often remains challenging in routine pulmonary CTA (Fig. 7), a constant refinement of contrast protocols has been observed in accordance with the evolution of CT technology, similar to that seen with aortic and coronary artery imaging [ ]. Reported contrast volumes range from 80 to 150 ml, and injection rates range from 2 to 5 ml/s [51, 52, ]. Because the mean attenuation of acute and chronic emboli was reported to be 33 and 87 HU, respectively, a theoretic minimum attenuation of 211 HU was suggested for the pulmonary arteries with diagnostically preferred pulmonary artery attenuations of HU [27, ]. Using 16- and 64-MDCT, Bae et al. [123] reported that a mean pulmonary artery opacification of 211 HU could be achieved with 1.0 ml/kg of 350 mg I/mL injected at 4 ml/s. Although scanning techniques applying fixed scan delays may be sufficient in most pulmonary CTA studies, precise and individualized adjustment is suggested when a tight contrast injection of less than 15 seconds injection duration is desired, or in patients with elevated cardiac output, cardiac dysfunction, pulmonary artery hypertension, or compromised venous flow [115, 124]. To W268 AJR:196, March 2011

10 Contrast Medium Delivery in Cardiothoracic CT Angiography individualize the scan delay, it has been recommended to measure contrast agent arrival time with either the test-bolus or bolustracking technique by placing an ROI in the main pulmonary artery or the right ventricle and calculating the delay accordingly [43, 53, 123, 125]. In a recent study, Henzler et al. [126] compared both test-bolus and bolustracking techniques for the determination of scan delay with dual-energy CTA of the lungs and concluded that homogeneous opacification can be achieved with either approach. For appropriate adjustment of the scan delay, it is important to consider that pulmonary enhancement declines rapidly after the enhancement peak if no additional contrast medium flows into the pulmonary artery, supporting the application of split-bolus protocols for pulmonary CTA as well [58, 127]. Figure 8 provides an example of timing-related variations in contrast enhancement. Summary With ongoing advances in CT scanner technology, contrast medium delivery remains an integral part of state-of-the art cardiothoracic CTA. With the multitude of different CT scanners, no single injection protocol strategy can currently be applied universally for cardiothoracic CTA. Although CT technology continues to evolve, the physiologic and pharmacokinetic principles of arterial enhancement will remain unchanged in the foreseeable future. Therefore, understanding these basic principles is crucial for designing optimal injection protocols according to each specific clinical scenario, independently of scanner technology. Current trends favor high injection rates and contrast materials with higher iodine concentrations to maximize the magnitude of vascular enhancement. 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