Contrast-enhanced ultrasonography is an ultrasonographic technique used to examine organ microcirculation and applied in veterinary medicine to detect lesions or pathological conditions within organs.1–3 Ultrasonographic contrast agents, which consist of encapsulated microbubbles stabilized by an outer shell, remain in the intravascular space and do not cross the vascular endothelium; this allows for dynamic visualization of microvasculature and quantification of tissue perfusion.4–6 Commercially available contrast agents have been used for CEUS of dogs, and the safety and usefulness of such agents have been assessed.3,7,8 A second-generation contrast agent that consists of perfluorobutane gas microspheres stabilized by a hydrogenated egg phosphatidyl serine membrane has better stability than other contrast agents as well as a delayed parenchymal (Kupffer) phase attributable to phagocytosis of the contrast agent within the reticuloendothelial system of the liver and spleen.8–12 Because of these features, perfluorobutane has been used for evaluation of many organs, including the spleen and liver of dogs.7,13–16
Compared with Doppler ultrasonography, CEUS has higher sensitivity for evaluation of blood circulation or microvascular structures within the kidneys; thus, it is a technique in human and veterinary medicine that has promise for use in the diagnosis of several kidney diseases or detection of renal lesions.3,17,18 Because renal CEUS is a functional imaging technique that can be used for the evaluation of perfusion and function of renal tissues, it can be applied to diffuse renal disorders involving blood flow or structural changes (eg, chronic kidney disease or ischemic renal injury).13,18–22 In human medicine, CEUS with perfluorobutane enables real-time evaluation and prolonged visual examination of the microcirculation of the renal cortex and medulla without causing nephrotoxicosis12,23; however, to our knowledge, use of perfluorobutane for evaluation of the kidneys of dogs has not been reported.
The clinical value of CEUS is complicated because of relatively large variation in several factors, including physiologic condition of an animal, contrast agents, and imaging and quantification settings of ultrasonographic platforms.4,6 Of these factors, injection variables for contrast agents (eg, catheter diameter or injection rate) may affect CEUS perfusion variables.4,6,24–26 During CEUS of humans, the bolus injection method, in which a flush solution is administered after contrast agent injection, is used widely for evaluation of organ perfusion.2 For this method, a 20-gauge catheter and rapid injection rate of the flush solution are recommended.27 However, achieving IV access with a 20-gauge catheter may not be feasible in some small animals. Thus, variation in injection of the flush solution may be a strong source of variability during renal CEUS for evaluation of microvascular flow in small animals because of their animal's smaller blood volume, compared with that of humans.24
The objective of the study reported here was to evaluate the effects of catheter diameter and injection rate of the flush solution on several renal perfusion variables for healthy dogs. It was hypothesized that a 24-gauge catheter would not affect renal perfusion variables but that injection rate of the flush solution would be associated with changes in renal perfusion variables.
Materials and Methods
Animals
Five adult Beagles (3 males and 2 females) were used in the study. Body weight ranged between 8.4 and 14.3 kg (mean ± SD, 11.6 ± 2.74 kg). All dogs were considered healthy on the basis of results of a physical examination, CBC, and serum biochemical analysis; measurement of systolic blood pressure; and no signs of renal disorders. Median body condition score was 6 (range, 4 to 7; scale, 1 to 9). Animal care and experimental procedures were approved by the Institutional Animal Care and Use Committee of Seoul National University.
Ultrasonographic examinations
Food was withheld from dogs for at least 12 hours before ultrasonographic examination. All images were acquired in a room maintained at a constant temperature and humidity. A 20-gauge indwelling catheter was placed in a cephalic vein. Sedation was achieved by IV administration of acepromazine maleate (0.01 mg/kg). Hair was clipped over the ventrolateral portion of the abdomen, and coupling gel was applied to the skin. Contrast agenta (0.0125 mL/kg, IV) was injected, which was followed by IV injection of a bolus (5 mL) of flush solution (saline [0.9% NaCl] solution). These injections were not used for analysis because they resulted in lower enhancement, compared with that of subsequent injections.28
Fifteen minutes after the initial injections were completed, physical examination variables (including respiratory and heart rates) were assessed, and systolic blood pressure was measured by use of an oscillometric technique.b Then, CEUS was performed with an ultrasound machinec and linear-array, 10-MHz transducer. Transmitted energy was reduced to a magnitude of 8% by use of a mechanical index setting between 0.17 and 0.19, pulse repetition frequency setting of 30 Hz, and gain of 62%. To reduce variation caused by manipulations, CEUS was performed on the left kidney of each dog, which was easy to access. Sequential CEUS images of the left kidney were continuously obtained for 90 seconds after rapid manual injection of a bolus of contrast agent (0.0125 mL/kg) via the 20-gauge catheter in the cephalic vein by use of a 3-way stopcock. Injection of contrast agent was immediately followed by injection of saline solution (5 mL) at a rate of 1 mL/s by use of a power injector.d Peak injection pressure of the venous catheter was measured by the power injector. After injection of saline solution was completed, physical examination variables and systolic blood pressure were reassessed. To avoid artifacts between subsequent injections, remnant microbubbles were destroyed by setting the acoustic power to the highest level and scanning the caudal abdominal aorta for 2 minutes. Confirmation that there were no remnant microbubbles was achieved by ultrasonographic examination of the caudal abdominal aorta for an additional 5 to 10 minutes. The next set of injections (contrast agent followed by flush solution) was then administered, except the injection rate of the saline solution was 3 mL/s. After data were collected for those injections, a final set of injections was administered, with an injection rate for the saline solution of 5 mL/s. After a 7-day washout period, CEUS images were obtained by repeating the same procedures, except a 24-gauge indwelling catheter was inserted in a cephalic vein. Thus, CEUS was repeated 3 times for each catheter diameter.
Image analysis
Acquired dynamic cine loops were analyzed at a rate of 30 frames/s by use of integrated software.e For each dog, 3 circular ROIs (area of each ROI, 0.11 cm2) were manually drawn in a row in the renal cortex, and 2 circular ROIs were manually drawn in the renal medulla at the same level (Figure 1). Depth of the ROIs (approx 2.5 cm) was measured as the distance between the body wall and left kidney. Location of the ROIs was selected so that vascular structures (eg, arcuate, interlobar, and interlobular arteries) and tissues adjacent to the vascular structures were excluded.
A CEUS image of the left kidney of a Beagle obtained at peak enhancement. Notice the placement of 3 ROIs (black circles) in the renal cortex and 2 ROIs (white circles) in the renal medulla. Area of each ROI was 0.11 cm2.
Citation: American Journal of Veterinary Research 80, 9; 10.2460/ajvr.80.9.825
The software created a time-intensity curve for each ROI. Time-intensity curves were analyzed to determine peak enhancement, TTP, AUC, wash-in, and washout. Wash-in and washout represented the slope of the ascending and descending portions of the time-intensity curves, respectively. Peak enhancement was the number of decibels of the maximum intensity of the time-intensity curve, and TTP was the interval from the start of contrast agent injection to the time of peak enhancement. Wash-in was calculated from data that were between 10% and 90% higher than peak enhancement. Data points with values > 90% of peak enhancement were used to calculate washout. A mean value was calculated for the 3 ROIs in the renal cortex; similarly, a mean value was calculated for the 2 ROIs in the renal medulla. The CV, defined as the SD divided by the mean, was determined for the repeated CEUS procedures.
Statistical analysis
Statistical analysis was performed by use of statistical software.f A repeated-measures ANOVA with a Tukey test and the Jonckheere-Terpstra test were used to compare CEUS perfusion variables obtained with the 20- and 24-gauge catheters at injection rates for the flush solution of 1, 3, and 5 mL/s. The CVs of the CEUS variables obtained for each CEUS procedure were calculated for each injection rate by use of a spreadsheet program.g A repeated-measures ANOVA with a Tukey test was used to evaluate effects of injection rate and catheter diameter on the CV. Mann-Whitney U tests were used to compare CVs of variables for the renal cortex and medulla. Values were considered significantly different at P < 0.05.
Results
Physical examination variables, systolic blood pressure, and venous catheter pressure
Respiratory rate, pulse rate, and systolic blood pressure measurements obtained before and after CEUS were evaluated. There was no significant difference in the mean ± SD values for the 5 dogs before and after CEUS for pulse rate (104.8 ± 25.5 beats/min and 99.9 ± 27.1 beats/min, respectively), respiratory rate (28.4 ± 4.7 breaths/min and 27.5 ± 4.7 breaths/min, respectively), or systolic blood pressure (124.2 ± 20.0 mm Hg and 124.8 ± 18.9 mm Hg, respectively).
Contrast enhancement was clearly visible for injections with both the 20- and 24-gauge catheters. Venous catheter pressure ranged from 0 to 1.77 mm Hg, with a mean pressure of 0.76 mm Hg for the 24-gauge catheter. For the 20-gauge catheter, venous catheter pressure ranged from 0 to 1.02 mm Hg (mean, 0.20 mm Hg). For both catheters, pressure was 0 mm Hg for an injection rate of 1 mL/s.
Perfusion variables
During CEUS, there was early enhancement of the interlobar arteries, and initial contrast enhancement of the renal cortex was homogeneous and intense. Moreover, initial contrast enhancement of the renal medulla was invariably more delayed than that of the renal cortex. The enhancement pattern of the renal medulla typically was heterogeneous, centripetal, and mildly hypoechoic, compared with that of the renal cortex.
Quantitative CEUS variables for the renal cortex and medulla at the 3 injection rates with 20-and 24-gauge catheters were summarized (Table 1). The CEUS variables did not differ significantly between catheter diameters. In the renal cortex, TTPs at an injection rate of 1 mL/s were significantly (P = 0.01) different from those at 3 and 5 mL/s, whereas there was no difference in variables for the renal medulla among injection rates. In the renal cortex, there were significantly lower TTPs at higher injection rates.
Mean ± SD values of perfusion variables for the renal cortex and renal medulla of 5 dogs on the basis of injection rate of the flush solution and catheter diameter.
| 24-gauge catheter | 20-gauge catheter | ||||||
|---|---|---|---|---|---|---|---|
| Location | Variable | 1 mL/s | 3 mL/s | 5 mL/s | 1 mL/s | 3 mL/s | 5 mL/s |
| Cortex | TTP (s) | 9.67 ± 1.25 | 8.20 ± 1.25* | 7.43 ± 1.51* | 9.83 ± 1.36 | 8.09 ± 0.76* | 7.05 ± 0.80* |
| PE | 27.48 ± 4.94 | 28.85 ± 9.17 | 32.07 ± 6.60 | 20.29 ± 4.44 | 26.36 ± 6.17 | 32.09 ± 8.87 | |
| AUC | 12,492 ± 856 | 12,428 ± 1,212 | 13,027 ± 838 | 11,241 ± 879 | 12,068 ± 1,229 | 13,315 ± 1,355 | |
| Wash-in | 42.90 ± 7.83 | 44.99 ± 12.30 | 45.39 ± 13.34 | 36.01 ± 9.66 | 44.34 ± 7.52 | 50.54 ± 6.16 | |
| Washout | −0.93 ± 0.04 | −1.02 ± 0.12 | −1.01 ± 0.15 | −0.88 ± 0.10 | −0.99 ± 0.06 | −0.95 ± 0.10 | |
| Medulla | TTP (s) | 15.00 ± 1.77 | 12.93 ± 1.86 | 12.98 ± 3.37 | 16.77 ± 1.40 | 14.32 ± 1.31 | 13.36 ± 1.28 |
| PE | 11.78 ± 1.21 | 11.11 ± 0.90 | 13.79 ± 2.05 | 9.52 ± 1.44 | 11.91 ± 2.65 | 14.44 ± 2.16 | |
| AUC | 12,300 ± 551 | 12,060 ± 425 | 12,313 ± 556 | 11,286 ± 827 | 11,596 ± 622 | 12,092 ± 974 | |
| Wash-in | 3.35 ± 0.69 | 4.12 ± 1.46 | 5.50 ± 2.56 | 3.37 ± 1.20 | 4.01 ± 1.81 | 6.32 ± 0.97 | |
| Washout | −0.27 ± 0.14 | −0.24 ± 0.04 | −0.27 ± 0.09 | −0.22 ± 0.08 | −0.32 ± 0.17 | −0.42 ± 0.12 | |
Wash-in represented the slope of the ascending portion of time-intensity curves. Washout represented the slope of the descending portion of time-intensity curves.
Within a catheter gauge, value differs significantly (P = 0.01; repeated-measures ANOVA with a Tukey post hoc test) from the value for an injection rate of 1 mL/s.
PE = Peak enhancement.
There are no units associated with the variables, except for TTP.
CVs for perfusion variables
The CVs for the CEUS variables were summarized (Table 2). There were no significant differences in CVs associated with catheter diameter. The CEUS variable with the lowest CV among injection rates was TTP for the renal cortex. Although there were no significant differences in CVs between injection rates of 1 and 3 mL/s or between 3 and 5 mL/s, there was a significant difference in CVs between the injection rates of 1 and 5 mL/s. Moreover, the CV of TTP obtained for the renal cortex for both catheter diameters decreased significantly (P = 0.01) as the injection rate increased. The CV for the wash-in of the time-intensity curve measured for the renal cortex was significantly higher than the CVs for TTP, peak enhancement, and AUC of the cortex. The CVs for wash-in and washout of the time-intensity curve measured for the renal medulla were significantly higher than the CVs for TTP, peak enhancement, and AUC of the medulla. Slope parameters for the time-intensity curve were significantly higher for the renal medulla than the renal cortex. Moreover, no significant differences were detected between the renal cortex and medulla for the other variables.
Mean ± SD values of the CV for perfusion variables of the renal cortex and renal medulla of 5 dogs on the basis of injection rate of the flush solution and catheter diameter.
| 24-gauge catheter | 20-gauge catheter | ||||||
|---|---|---|---|---|---|---|---|
| Location | Variable | 1 mL/s | 3 mL/s | 5 mL/s | 1 mL/s | 3 mL/s | 5 mL/s |
| Cortex | TTP | 8.8 ± 1.8 | 5.3 ± 2.2 | 4.7 ± 1.9* | 11.4 ± 9.3 | 5.8 ± 4.0 | 3.5 ± 1.5* |
| PE | 14.3 ± 5.7 | 11.9 ± 6.8 | 10.6 ± 9.5 | 12.7 ± 8.0 | 12.6 ± 4.2 | 12.2 ± 6.7 | |
| AUC | 16.6 ± 10.8 | 18.0 ± 4.3 | 10.8 ± 6.8 | 14.1 ± 8.4 | 18.7 ± 8.6 | 20.2 ± 7.3 | |
| Wash-in† | 39.8 ± 16.9 | 35.1 ± 23.7 | 16.9 ± 5.6 | 20.9 ± 8.8 | 31.0 ± 12.3 | 26.6 ± 7.5 | |
| Washout | 16.0 ± 6.9 | 25.5 ± 24.8 | 13.3 ± 13.0 | 14.1 ± 9.4 | 12.3 ± 9.3 | 16.9 ± 10.1 | |
| Medulla | TTP | 15.9 ± 5.2 | 16.6 ± 6.4‡ | 18.7 ± 15.1‡ | 17.0 ± 11.5 | 10.3 ± 6.2 | 13.5 ± 4.7‡ |
| PE | 13.9 ± 5.5 | 14.4 ± 6.3 | 14.2 ± 7.3 | 7.5 ± 4.3 | 12.4 ± 6.4 | 12.0 ± 5.7 | |
| AUC | 11.8 ± 7.3 | 13.5 ± 3.4 | 9.4 ± 6.5 | 7.8 ± 4.7 | 12.0 ± 5.1 | 14.4 ± 6.9 | |
| Wash-in† | 55.1 ± 14.1‡ | 56.0 ± 17.6‡ | 46.7 ± 32.9‡ | 59.0 ± 21.3‡ | 40.2 ± 17.3‡ | 56.0 ± 30.8‡ | |
| Washout† | 57.7 ± 18.8‡ | 62.1 ± 53.9‡ | 45.2 ± 26.5‡ | 45.7 ± 32.0‡ | 33.0 ± 14.8‡ | 41.3 ± 19.1‡ | |
Values reported are percentages.
Within a catheter gauge, value differs significantly (P < 0.05; repeated-measures ANOVA with a Tukey post hoc test) from the value for an injection rate of 1 mL/s.
Values differ significantly (P < 0.05; Mann-Whitney U test) from values for TTP, PE, and AUC.
Value differs significantly (P < 0.05) from the corresponding value for the renal cortex.
Discussion
Differences in renal perfusion variables attributable to changes in catheter diameter and injection rate of flush solution during CEUS with perfluorobutane in dogs were evaluated in the study reported here. Among the renal perfusion variables examined, TTP and the reproducibility of TTP were affected by injection rates of the flush solution. Renal perfusion variables other than TTP and the reproducibility of those variables were not affected by catheter diameter for 20- and 24-gauge catheters.
For the study reported here, TTPs decreased significantly as a function of injection rate from 1 to 5 mL/s. Injection rates can affect perfusion variables,4,24,26 and manual bolus injection of contrast agents and saline solution is widely used in studies of dogs3,20,21,29,30 and cats.22,28,31–35 However, injection procedure can be a factor that increases the variation observed for CEUS performed at small animal veterinary clinics.6,18,27 The association between injection rate and TTP in the present study is in agreement with results of previous studies of CEUS for experimental animals; however, the association between injection rate and other variables, including peak enhancement, is in conflict with results of other studies.4,26 Although the cause of this discrepancy is unknown, animals used in previous studies had extremely low body weights and may have been more sensitive to the amount of contrast agent administered. Moreover, this discrepancy may have been attributable to physiologic differences among species or body weights.
Perfusion of the renal cortex, which is the main structure receiving blood flow to the kidneys, is related to renal dysfunction, which causes changes in cortical perfusion.33,36,37 It is important to improve reproducibility of TTP for the renal cortex because TTP is delayed in dogs and cats with nephropathy (eg, chronic kidney disease), compared with TTP for healthy dogs and cats, and early changes in renal perfusion are caused by nephropathy.19,22,29,36,38 In the study reported here, CVs for TTP of the renal cortex were influenced by injection rate of the flush solution. An injection rate of 5 mL/s resulted in less variation, compared with variation for an injection rate of 1 mL/s. Peak enhancement and TTP of the time-intensity curve depend on the injection rate of a contrast agent. A slow injection rate for a contrast agent induces low concentrations of bubbles during perfusion, which creates heterogeneous and inadequate enhancement; this situation can be corrected with a rapid injection rate.6,26,39 Findings for the present study indicated that an injection rate of 5 mL/s was sufficient to reduce TTP variation in renal CEUS of Beagles. Therefore, considering the importance of TTP, results of the present study would be expected to have an important role in future studies of renal CEUS and diagnosis of renal disease.
Use of 20- and 24-gauge catheters did not result in significant changes to renal CEUS variables in the present study. Catheter diameter is one of the factors related to an increase in hydrostatic pressure that causes microbubble destruction.25,40,41 In other studies of renal perfusion in dogs20,21,30 and cats,22,28,34,35 20- or 22-gauge catheters were used during renal CEUS to avoid microbubble destruction. However, these catheter diameters are not likely to be applicable for use at small animal clinics, and use of catheters of a minimal diameter required for administration of contrast agent and flush solution should allow for easier and less painful insertion of such catheters in the veins of small animals. For dogs and cats, CEUS renal perfusion has been performed by use of 24- or 25-gauge catheters.29,31,32 However, investigators of those studies29,31,32 did not confirm whether microbubbles were destroyed. Variables for the time-intensity curve derived by use of the bolus technique allow for estimation of blood flow and volume within organs.2 Assuming that CEUS signal intensity is proportional to the amount of intravascular microbubbles, peak enhancement and AUC correlated with ROI blood volume can be used to evaluate whether microbubble destruction has occurred.2,25 In the study reported here, there were no significant differences in peak enhancement and AUC between the 20- and 24-gauge catheters, which indicated that catheter diameter did not affect microbubble destruction. However, there is debate about the association between injection rate and microbubble destruction, and it is possible that microbubble destruction occurs at high or low injection rates with small-diameter catheters.40,41 In the present study, there were no differences in peak enhancement and AUC among injection rates of the flush solution, which indicated that microbubble destruction was not affected by the flush solution injection rates used.
Contrast-enhanced ultrasonography is associated with a relatively high degree of variability, and minimization of variability and improvements of reproducibility are important issues for the use of CEUS in clinical research.2,4,6 In the present study, slope parameters had the highest variation and had relatively higher variation than those of TTP, peak enhancement, and AUC. For the renal cortex and medulla, the CV of peak enhancement or AUC was lower, compared with that previously reported33 for feline kidneys, which ranged from 41% to 67% for manual injections. Compared with results for a study36 of the kidneys of dogs, variability of peak enhancement or AUC of the renal cortex and medulla was lower in the present study. For the renal cortex, the CV of peak enhancement or AUC was similar to that observed in a study24 of the renal cortex of mice that involved use of a controlled injection method. In that study,9 CV for peak enhancement or AUC ranged from 8% to 16%. Variation of all perfusion variables is higher for the renal medulla of dogs and cats, compared with variation of perfusion variables for the renal cortex25,33; however, in the present study, no variables were significantly increased for the renal medulla, except for the slope parameters.
For the study reported here, there was an association between the slope parameters for the renal cortex and medulla, which likely were related to anatomic and physiologic features of medullary blood flow.33,36 However, the reason there were no differences in TTP, peak enhancement, and AUC between the renal cortex and medulla is unknown. In mice and rats, manual injection of contrast agents increases variation in renal CEUS perfusion variables.4,24 Such bias for CEUS measurements could be overcome by the use of controlled injections.4,24 Therefore, it is possible that the controlled injection method used in the present study influenced the results.
To our knowledge, the study reported here represented the first report of renal CEUS with perfluorobutane for evaluation of the kidneys of healthy dogs. Perfluorobutane has a phospholipid shell for each microbubble and provides stable long-term contrast enhancement, compared with properties of first-generation contrast agents.12 In contrast to other second-generation agents (eg, sulfur hexafluoride or perflutren lipid microspheres), perfluorobutane has a delayed parenchymal phase caused by the uptake of the contrast agent by Kupffer cells.8,42 The contrast enhancement pattern was similar to that in studies29,36,43 of CEUS evaluation of the kidneys of healthy dogs by the use of other second-generation contrast media. Perfluorobutane is tolerated better and has higher stability than other second-generation contrast agents.9–11 In human medicine, renal perfusion performed by use of dynamic CEUS after bolus injection of perfluorobutane enables prolonged visual examination of the renal microcirculation.12,23 In special situations (eg, deep lesions, obese patients, or cirrhotic lesions), a relatively high mechanical index value is required.44 For these reasons, renal CEUS with perfluorobutane may be more appropriate for evaluation of renal perfusion in veterinary medicine.
Excessive pressure in a venous catheter can cause complications such as extravasation, air embolism, or pain.45,46 In the study reported here, pressure in the catheter was lower than the pressure that can cause adverse effects.45,46 Moreover, there was no evidence of vascular rupture after CEUS procedures, and the absence of significant changes in systolic blood pressure, respiratory rate, or pulse rate before and after CEUS suggested that the dogs were not uncomfortable or irritated. Therefore, the catheters and injection rates used in the present study did not cause complications.
The study reported here had some limitations. First, it included a small number of Beagles, which typically weigh more than many small-breed dogs. Therefore, the study results did not confirm that there would be no bubble destruction in small-breed dogs when a 24-gauge catheter is used. It also was unclear whether the injection rate of the flush solution would affect renal CEUS perfusion. Although the main factors for bubble destruction are injection rate and inner diameter of the catheter, it is thought that differences in body size do not substantially affect bubble destruction.25,41 Findings for the present study did not indicate the manner in which flush solution injection rate in dogs smaller than Beagles would affect renal CEUS perfusion variables; however, effects attributable to injection rate of the flush solution would be expected to be evident in small-breed dogs because they have small blood volumes. Additional studies may provide a clear correlation between injection rates and perfusion variables.
The study reported here indicated that a CEUS procedure performed with a 24-gauge catheter did not alter renal perfusion variables of healthy Beagles. Results also indicated that the use of a flush solution injection rate of 5 mL/s enhanced reproducibility of the perfusion variables. Therefore, we believe a 24-gauge catheter can be used. We recommend that a flush solution injection rate of 5 mL/s be used for Beagles to provide better precision. Additional studies will be needed to determine the efficacy for use of 24-gauge catheters and a flush solution injection rate of 5 mL/s for other breeds of dogs and dogs with other conformations.
Acknowledgments
Supported in part by the Research Institute for Veterinary Science at Seoul National University. Funding sources did not have any involvement in the study design, data analysis and interpretation, or writing and publication of the manuscript.
The authors declare that there were no conflicts of interest.
ABBREVIATIONS
| AUC | Area under the time-intensity curve |
| CEUS | Contrast-enhanced ultrasonography |
| CV | Coefficient of variation |
| ROI | Region of interest |
| TTP | Time to peak enhancement |
Footnotes
Sonazoid, Daiichi Sankyo Corp, Tokyo, Japan.
SunTech Vet20, SunTech Medical Inc, Morrisville, NC.
ProSound Alpha 7, Hitachi-Aloka, Tokyo, Japan.
Stellant, Medrad Inc, Pittsburgh, Pa.
SOP-ALPHA 7–14, Hitachi-Aloka, Tokyo, Japan.
IBM SPSS statistics, version 23.0, IBM Corp, Armonk, NY.
Microsoft Excel, version 2013, Microsoft Corp, Redmond, Wash.
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