The optimal contrast media policy in CT of the liver. Part I: Technical notes

Abstract

Latest developments of multidetector computed tomography (MDCT), which is today considered a real volumetric technique, have revolutionized abdominal imaging.

Technological improvements such as higher spatial resolution, larger volume coverage and higher temporal resolution, have reduced scan times allowing CT studies of the abdomen within a single breath-hold.

Furthermore, the increased number of slices, the submillimetric collimation, and the use of multiple dynamic post-contrast phases per single examination, may all contribute to increase the radiation exposure of single patients.

The aim of this review is to discuss different parameters affecting contrast media enhancement, as vascular enhancement, parenchymal enhancement and timing, in order to minimize the amount of contrast medium injected and the radiation exposure.

Keywords

MDCT contrast medium injection protocols vascular enhancement parenchymal enhancement

With the advent of multidetector computed tomography (MDCT) the accuracy of abdominal imaging has been increased significantly. In particular the identification and characterization of liver lesions is strictly dependent on both scanning and contrast medium (CM) injection parameters.

The goal of any MDCT examination is to achieve the best image quality and as high lesion conspicuity as possible with the lowest radiation exposure and the lower CM volumes. In the recent past many CMs with high iodine concentration have been developed to reduce both volume and injection flow. Because side-effects of CM are mainly dependent on the total iodine dose administered to the patient, the optimization of CM volumes is mandatory.

Advantages and disadvantages of different CMs iodine concentration in many different clinical situations have been revealed in the literature (1–4), but, despite those results, it is evident that the most important parameter influencing parenchymal enhancement is the total amount of iodine delivered and its injection flux.

The aim of this review paper is to discuss different parameters affecting contrast media enhancement and image quality to minimize the amount of contrast medium injected and radiation exposure.

Factors affecting contrast enhancement

Vascular and parenchymal enhancements are generally affected by different kinetics. Vascular enhancement is essentially determined by the iodine dose delivered per unit of time while parenchymal enhancement is influenced by the total iodine dose. However, both are significantly influenced by patient-related factors such as body size, gender and age.

Vascular enhancement

Prevalently two variables determine the time-course of vascular enhancement: the iodine delivery rate (IDR) and the injection duration (ID). Arterial enhancement is also influenced by patients' related variables such as cardiovascular status (i.e. cardiac output) and individual body size indexes (i.e. distribution volume) (5–10).

Vascular enhancement is directly proportional to IDR (gI/s). IDR is under the operator control and can be determined by modifying the injection flow rate (FR) according to the iodine concentration of a given contrast medium. An increase of the FR (mL/s) is directly proportional to an increase of the vascular enhancement. As a general rule, if the acquisition of an arterial phase for body imaging is required, IDR should not be less than 1.2 gI/s; better if around 1.6 gI/s since it provides higher conspicuity of hypervascular lesions (11, 12). The required value can be virtually obtained with any concentration of contrast medium according to the following formula:

where [I] is the contrast medium concentration (expressed in mgI/mL) and FR is the injection flow rate. As an example, in order to achieve an IDR of 1.6 gI/s, it would be necessary to inject a contrast medium with a concentration of 320 mgI/mL at a flow rate of 5.0 mL/s, and a contrast medium with a concentration of 400 mgI/mL at a flow rate of 4.0 mL/s.

Once the injection FR is chosen, the contrast volume should also be set on the injector screen. If the acquisition of an arterial phase is required, contrast volume depends from the ID according to the following formula:

For example: if FR is 4.0 mL/s (for a 400 mgI/mL CM) and ID is 13 s, the total volume needed is 52 mL.

Injection duration influences vascular enhancement only in longer acquisitions (>10 s): the longer the ID the higher the arterial enhancement. This is due to the cumulative effects of bolus recirculation phenomenon which contributes to an increase, quantified around 10–20%, of the peak of arterial enhancement and the magnitude of intravascular enhancement. For abdominal acquisition times (>5 s for liver imaging) this parameter is not as important. Injection duration should be longer than the scan time and scan acquisition should be delayed until the maximum intravascular attenuation is achieved. As a ballpark rule for abdominal angiographic acquisitions, scan delay should be delayed 8 s from the reach of a 100 HU threshold in the aorta. Injection duration should be calculated as follows: for a 5-s acquisition, injection duration should be 5 s + 8 s = 13 s (13). Scan delay should be modified according to the clinical needs, and in particular, according to the organ to be studied. This will be discussed in a specific section.

Patient-related factors contribute to the magnitude of vascular and parenchymal enhancement; the most important are patient body size and cardiac output. Cardiac output is the most important factor affecting the timing of contrast enhancement and cardiovascular circulation. A reduction of cardiac output results in a delayed contrast material arrival, a higher peak arterial enhancement and a prolonged parenchymal enhancement. The slower the CM circulates, the slower its clearance, and the higher its concentration (10, 14, 15). The magnitude of aortic peak and parenchymal enhancement, increase substantially in patients with reduced cardiac output, while the magnitude of hepatic enhancement peak increases only slightly. A reduction of 60% of the cardiac output increases the magnitude of aortic peak enhancement of about 30% and hepatic enhancement of only 2% (16). The factors which affect cardiac output the most are sex and age. It has been demonstrated that CM bolus arrives slightly earlier in female patients than in male patients because of a smaller (around 5–10%) distribution volume (17–19). A recent study (20) demonstrated a reduction of cardiac output proportional to age, suggesting that iodine dose and injection rate can be reduced in elderly patients by 10% to achieve enhancement of the same magnitude.

IDR should also be modified according to the patient's body size. As previous studies demonstrated (21), IDR should be weighed according to patient's lean body weight (LBW) which provides, among other body size indexes (e.g. total body weight [TBW]; blood volume [BV]), the best hepatic arterial enhancement with reduced patient-to-patient variability.

Flow rates for contrast medium with different iodine concentrations and TBW are suggested in Table 1.

Table 1.
Suggestions for injection flow rates of contrast medium, with different iodine concentrations, according to TBW

TBW <55 56–65 66–85 86–95 >95

Iodine concentration (mgI/mL) IDR (gI/sec) 1.2 1.4 1.6 1.8 2.0

300 FR (mL/s) 4 4.7 5.3 6 6.7

320 3.7 4.4 5 5.6 6.2

350 3.4 4 4.6 5.1 5.7

370 3.2 3.8 4.3 4.8 5.4

400 3 3.5 4 4.5 5

TBW = total body weight, IDR = iodine delivery rate, FR = flow rate

Parenchymal enhancement

Parenchymal enhancement is governed by the relationship of total iodine dose (mgI) versus total volume of distribution (intravascular and interstitial spaces).

Historical studies have (9) demonstrated that it is necessary to deliver an adequate amount of Iodine, in the range of 500–600 mgI per kg of TBW, to achieve an optimal parenchymal enhancement of the liver (around 50–60 HU). To calculate the volume of contrast medium required if using a CM with a concentration of 300 mgI/mL, it is necessary to deliver 2 mL/kg of TBW. This figure (2 mL/kg) should be adapted to the concentration of Iodine: thus resulting 1.7 mL/kg for 350 mgI/mL and 1.5 mL/kg for 400 mgI/mL.

However, it has been demonstrated that TBW (21) is not the optimal body size index for adjusting iodine dose because blood volume and liver weight are not directly proportional to TBW. For example, obese patients may have abundant body fat, which has a small vascular and interstitial space and thus contributes little to dispersing or diluting the contrast material in the blood. In these patients, adjusting the iodine dose proportionally to TBW may lead to an overestimation of the amount of contrast material needed. Some authors (21, 22) have reported that calculating the contrast material dose on the basis of LBW leads to increased patient-to-patient uniformity of hepatic parenchymal and vascular enhancement. LBW can be either measured or calculated. To measure LBW, the use of an electronic body fat monitor which estimates the body fat percentage (BFP) is necessary but is not easily available in every structure. Nonetheless, LBW can be calculated applying the following formula:

Body fat percentage can also be estimated on the basis of the patient's weight (in kg) and the visual assessment of their fitness level (23) as summarized in Table 2.

Table 2.
Values of LBW on the basis of patient's weight (in kg) and BFP, estimated by visual assessment of the fitness

Weight

Men Women

Fitness level (BFP) LBW <55 56–65 66–85 86–95 >95 <55 56–65 66–85 86–95 >95

Slim (M = 3%,W = 11%) 53 58 68 87 92 49 53 62 80 85

Athlete (M = 9%,W = 17%) 50 55 64 82 86 46 50 58 75 79

Medium size (M = 15%,W = 22%) 47 51 59 76 81 43 47 55 70 74

Fatty (M = 22%,W = 28%) 43 47 55 70 74 40 43 50 65 68

Obese (M = >32%,W = >35%) 41 45 52 67 71 37 40 48 61 65

BFP = body fat percentage, LBW = lean body weight

It has been demonstrated that no significant differences were found between the liver parenchyma enhancement obtained applying the measured LBW or the calculated LBW (22).

Once the patient's LBW is evaluated, the amount of iodine required to achieve an adequate enhancement of the liver parenchyma may be calculated by using the following equation:

where I is the amount of Iodine (gr) and ΔHU represents the maximum hepatic enhancement (MHE) desired (which should be around 50–60 HU) (9). The amount of iodine needed, divided by the CM concentration (in gr), results in the exact CM volume in mL.

Examples of CM volume calculated on the basis of LBW are summarized in Table 3.

Table 3.
Amount of CM (iodine dose and CM volume) calculated according to ranges of LBW

LBW range Iodine dose (g) CM concentration (mgI/dL)

CM volume (mL) 300 320 350 370 400

35–39 26.12 87 82 75 71 65

40–44 29.18 97 91 83 79 73

45–49 33.18 111 104 95 90 83

50–54 36.36 121 114 104 98 91

55–59 40.48 135 126 116 109 101

60–64 44.01 147 138 126 119 110

65–69 47.07 157 147 134 127 118

70–74 50.60 169 158 145 137 126

75–79 54.13 180 169 155 146 135

80–84 57.19 191 179 163 155 143

LBW = lean body weight; CM = contrast medium

Contrast medium osmolarity and viscosity

Theoretically the contrast medium enhancement effect is influenced also by its intrinsic chemical and physical properties. Osmolarity and viscosity, indeed, can modify the behaviour of the contrast medium-blood mixture. The exact influence of these properties on the enhancement effect is complex because of the double behaviour of the blood which is a non-Newtonian fluid. It is known that blood viscosity depends on erythrocytes which change their viscous properties at a certain temperature according to the shear rate. At high shear rates (e.g. in main arteries) blood behaves as a Newtonian fluid and its viscosity is mainly influenced by the shearing deformation of the erythrocytes. At low shear rates, as in the capillary, blood behaves as a non-Newtonian fluid because erythrocytes tend to aggregate and viscosity increases with decreasing shear rates. As Poiseuille's law states flow is inversely proportional to viscosity. Thus if high viscosity contrast mediums are mixed to blood its viscosity should increase and flow should be reduced proportionally. This was confirmed by a previous experience (24) which demonstrated a temporary flow decrease, immediately after the CM injection (10 s), followed by a rapid increase till the peak enhancement. This has been related to the stimulation of nitric oxide release, due to the wall stress, which causes vasodilatation (25). Thus, the higher the viscosity, the stronger the vasodilatation, the higher the flow (24). However this effect has not been demonstrated to be significantly influent on enhancement (26). In the microcirculation viscosity is mainly influenced by cells deformation, frictional contact and tendency to aggregate. In this situation CM osmolarity, with its effects on blood cell morphology and aggregation, influences CM–blood mixture viscosity more than CM viscosity. Moreover it has been demonstrated that in capillaries CM–blood mixture viscosity decreases with increasing CM concentration because of the corresponding higher osmolarity (27). The increase in osmolarity leads to a movement of extracellular fluid into the vascular space, which increases flow because of the nitric oxide related vasodilatation. As a drawback, fluid moving in the vascular space decrease CM iodine concentration because of dilution. Thus, the lower the CM osmolarity, the lower its dilution, with higher attenuation, but with slower flow because of a lower vasodilation.

Saline injection

During fast acquisition scans, a substantial volume of the injected CM remains in the dead space of right heart, peripheral veins, and injection tubing. Flushing the venous system with saline immediately after CM pushes the CM column into the systemic circulation (28–31). Thus, the use of a saline flush is helpful in the optimization of CM volumes allowing a reduction of iodine dose with no significant influences on the level of contrast enhancement (27). The reduction of CM volume has been reported to be between 12 mL (32) and 50 mL (28, 33) with a positive effect on the chance of contrast medium induced nephropathy.

The most convenient technique for routine saline ﬂushing after CM injection uses new programmable double-piston power injectors (one syringe for CM, one for saline).

In the field of abdominal CT, there is little evidence of the influence of saline flushing on the vessel and parenchymal enhancement. Previous experiences (34, 35) investigating the effect of saline flushing on aortic, portal, and hepatic enhancement, reported a significant increase of aortic peak and no evidence of improvement on hepatic enhancement. Another recent study (11), confirmed a non-significant increase of hepatic enhancement magnitude while finding a significant increase of portal vein enhancement during the early and late arterial phases. A systematic review published in 2009 (36), has shown that a saline chaser does not improve the magnitude of liver parenchyma enhancement in clinical imaging; whereas, in time density analysis, saline flush significantly improves the time to peak of the liver, portal vein, and aorta enhancement. Furthermore, the CM left in the dead space contributes to vascular enhancement with a slow and late flowing. The cleaning of this CM volume reflects in a more rapid decline of intravascular attenuation after the peak, and scanning during this period may result in an insufficient contrast enhancement (31).

Timing

The determination of the optimal temporal window for liver scanning is mandatory to correctly identify and characterize focal or diffuse disease (13, 21, 28).

Contrast medium transit time (tCMT) is the time between the start of intravenous administration of a CM bolus and its arrival in the vascular region of interest. Thus, especially in patients with cardiovascular disease, scan delay should be based on the patient's tCMT. The tCMT can be determined using a test bolus injection or automated bolus triggering techniques.

The use of fixed delay time cannot be recommended any longer, since it cannot guarantee optimal separation between dynamic phases due to inherent variability among individuals, such as patient size and cardiovascular status.

For this reason, a more rational use of MDCT can be accomplished by using a test bolus or a bolus tracking software (37).

The test bolus technique is based on the injection, at the same flow rate of the diagnostic injection calculated, of a small CM bolus (15–20 mL) while acquiring multiple low-dose sequential scans at the starting level of the diagnostic scan. The time-enhancement curve obtained is a reliable method to determine the tCMT from the intravenous injection site to the arterial territory of interest (38). The tCMT equals the time-to-peak enhancement interval, measured in a region of interest (ROI) placed within a reference vessel. Furthermore, time-attenuation curves obtained from one or more regions of interest can be used for individual bolus-shaping techniques using set mathematical models (39). A test bolus is particularly useful in determining the tCMT if unusual CM injection sites need to be used (e.g. lower extremities) or for very short (<3 s) scan times when a bolus triggering software is not suitable.

Many CT scanners have an automatic bolus triggering software built into their system. This method consists in the real-time detection of placing a circular ROI into the target vessel on a non-enhanced image. After 5–10 s from the start of the CM injection, a series of low-dose sequential scans are acquired every 1–3 s; whereas the attenuation within a ROI is monitored or inspected visually. The tCMT equals the time when a predefined enhancement threshold is reached (e.g. 100 HU), plus a diagnostic delay which should be determined according to the specific organ to be studied. The diagnostic delay is the time between the reach of a predefined enhancement threshold and the start of the MDCT acquisition; it depends on the scanner model and on the longitudinal distance between the monitoring series and the starting position of the actual MDCT series. Bolus triggering is a very robust and practical technique for routine use and has the advantage of not requiring an additional test-bolus injection (40–42).

Scanning parameters and radiation issue

Similarly to CM injection parameters, the optimization of scanning parameters is also mandatory to obtain high image quality with the lowest dose achievable. Among all parameters modifiable by the operator, the most important are: slice thickness, pitch, tube current modulation, and tube voltage optimization.

Because 64-row MDCTs use the full detector array in all cases in which there is no difference in dose exposure compared with protocols using thicker collimation, it may be advantageous to take full benefit of a 64-slice acquisition. Inherent noise, clearly evident in images obtained with a sub-millimetre collimation, can be simply reduced by increasing the thickness of reconstructed images. Thus, for liver imaging, the thinnest possible collimation (i.e. 64 × 0.5 or 64 × 0.625) should be used. To improve image quality, intrinsic noise can be reduced reconstructing images with higher thickness (1.25 mm or 2.5 mm). A thinner (1 mm or less) slice thickness should be reserved for cases where multiplanar reformations and three-dimensional reconstructions are needed. For the assessment of liver parenchyma, considering the large number of slices associated with thinner collimation, 2.5 mm slice thickness should be considered the optimal compromise.

One of the most important parameters in MDCT is pitch, which corresponds to the ratio of the table increment (movement in millimetres per rotation) to the total nominal bean width. In spiral CT, both dose and image noise depends on pitch. The higher the pitch, the shorter the scan time (X-ray irradiation time) results. If pitch is higher than 1, there are more gaps in the data with fewer redundant points to average, so image noise increases (43). Thus, pitch value must be adapted and optimized to reduce both scan time and radiation exposure maintaining acceptable image noise levels.

Different dose reduction strategies for CT scanning have been introduced, and the use of low-dose scanning protocols with acceptable image quality have been extensively investigated (44, 45). The most commonly used dose reduction technique is the automatic tube current modulation (ATCM) technique, which employs angular (adjustment of tube current in the x–y axes) or z axis (modulation in the scanning direction) mA modulation. In ATCM with z-axis modulation, the tube current is automatically adjusted according to regional body anatomy, to maintain a constant user-specified quantum image noise level and to improve radiation dose efficiency. A noise index (NI) is provided to allow users to select an acceptable noise level on the reconstructed images. The NI value represents the value of image noise (standard deviation) in the central region of an image obtained by scanning a uniform phantom. The user selects an NI to define image quality and a range of acceptable tube current before the scan. The tube current necessary to obtain images with the selected NI value is determined using the scout images, which include information on patient density, size, and shape. Therefore, the system is designed to ensure that all images have a constant noise level regardless of differences in patient size and anatomy (46, 47). Tube current modulation systems are an effective tool to reduce patient dose without compromising image quality.

Tube voltage is another fundamental parameter to be optimized because it has been demonstrated that by using lower kV values the radiation burden is reduced and lower CM volume and IDR can be used (48–50). There is an exponential relationship between kilovolt and radiation dose; dose is reduced by the square of the tube voltage change (i.e. square of the ratio of final and initial peak voltage), and image noise is approximately inversely proportional (51). The effects on image quality are complex since a reduction in kilovoltage (kV) increases image noise, but also improves tissue contrast. Furthermore, for a given reduction of kV value there is a proportional increase of CM attenuation values because X-ray voltage gets closer to the iodine k edge of 33 keV (39, 52). From a practical point of view, every mg of iodine corresponds to an increase of 26 HU at 120 kV, 32 HU at 100 kV and 41 HU at 80 kV (46). A fundamental requirement to use reduced kV values is the patient's body size. For higher BMI values (>25) a kV value of 120 is recommended, while for lower BMIs 100 kV can be used. As mentioned for lower kV values, image noise increases proportionally; thus higher mA values should be used to increase image quality with a minimal increase in dose.

Conclusions

The last ameliorative technological developments of MDCT, as higher spatial resolution, larger volume coverage and faster scanning time, have revolutionized abdominal imaging, improving diagnostic accuracy.

To obtain an optimal vascular ad parenchymal enhancement, we have to take into consideration many parameters: patient related factors (gender, age, BMI, LBW), CM injection protocols (Iodine dose, Iodine administration rate), and scanning parameters (slice thickness, pitch, tube current, tube voltage, noise index).

Today, it's possible to obtain optimal images quality, reducing the amount of CM injected according to LBW and reducing radiation exposure according to patient's BMI.

Conflict of interest: None.

	TBW	<55	56–65	66–85	86–95	>95
300	FR (mL/s)	4	4.7	5.3	6	6.7
320		3.7	4.4	5	5.6	6.2
350		3.4	4	4.6	5.1	5.7
370		3.2	3.8	4.3	4.8	5.4
400		3	3.5	4	4.5	5

		Weight
Fitness level (BFP)	LBW	<55	56–65	66–85	86–95	>95	<55	56–65	66–85	86–95	>95
Slim (M = 3%,W = 11%)		53	58	68	87	92	49	53	62	80	85
Athlete (M = 9%,W = 17%)		50	55	64	82	86	46	50	58	75	79
Medium size (M = 15%,W = 22%)		47	51	59	76	81	43	47	55	70	74
Fatty (M = 22%,W = 28%)		43	47	55	70	74	40	43	50	65	68
Obese (M = >32%,W = >35%)		41	45	52	67	71	37	40	48	61	65

LBW range	Iodine dose (g)	CM concentration (mgI/dL)
		CM volume (mL)	300	320	350	370	400
35–39	26.12		87	82	75	71	65
40–44	29.18		97	91	83	79	73
45–49	33.18		111	104	95	90	83
50–54	36.36		121	114	104	98	91
55–59	40.48		135	126	116	109	101
60–64	44.01		147	138	126	119	110
65–69	47.07		157	147	134	127	118
70–74	50.60		169	158	145	137	126
75–79	54.13		180	169	155	146	135
80–84	57.19		191	179	163	155	143

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	TBW	<55	56–65	66–85	86–95	>95
Iodine concentration (mgI/mL)	IDR (gI/sec)	1.2	1.4	1.6	1.8	2.0
300	FR (mL/s)	4	4.7	5.3	6	6.7
320		3.7	4.4	5	5.6	6.2
350		3.4	4	4.6	5.1	5.7
370		3.2	3.8	4.3	4.8	5.4
400		3	3.5	4	4.5	5

		Weight
		Men					Women
Fitness level (BFP)	LBW	<55	56–65	66–85	86–95	>95	<55	56–65	66–85	86–95	>95
Slim (M = 3%,W = 11%)		53	58	68	87	92	49	53	62	80	85
Athlete (M = 9%,W = 17%)		50	55	64	82	86	46	50	58	75	79
Medium size (M = 15%,W = 22%)		47	51	59	76	81	43	47	55	70	74
Fatty (M = 22%,W = 28%)		43	47	55	70	74	40	43	50	65	68
Obese (M = >32%,W = >35%)		41	45	52	67	71	37	40	48	61	65