The feasibility of low iodine dynamic CT angiography with test bolus for evaluation of lower extremity peripheral artery disease

Abstract

Objective

This study aims to determine if low iodine dynamic computed tomography angiography performed after a fixed delay or test bolus acquisition demonstrates high concordance with clinical computed tomography angiography (using a routine amount of iodinated contrast) to display lower extremity peripheral arterial disease.

Methods

After informed consent, low iodine dynamic computed tomography angiography examination (using either a fixed delay or test bolus) using 50 ml of iodine contrast media was performed. A subsequent clinical computed tomography angiography using standard iodine dose (115 or 145 ml) served as the reference standard. A vascular radiologist reviewed dynamic and clinical computed tomography angiography images to categorize the lumen into “not opacified”, “<50% stenosis”, “ 50 ̶70% stenosis”, “>70% stenosis”, and “occluded” for seven arterial segments in each lower extremity. Concordance between low iodine dynamic computed tomography angiography and the routine iodine reference standard was calculated. The clinical utility of 4D volume-rendered images was also evaluated.

Results

Sixty-eight patients (average age 66.1 ± 12.3 years, male; female = 49: 19) were enrolled, with 34 patients each undergoing low iodine dynamic computed tomography angiography using fixed delay and test bolus techniques, respectively. One patient assigned to the test bolus group did not undergo low iodine computed tomography angiography due to unavailable delayed time. The fixed delay was 13 s, with test bolus acquisition resulting in a mean variable delay prior to image acquisition of 19.5 s (range; 8–32 s). Run-off to the ankle was observed using low iodine dynamic computed tomography angiography following fixed delay and test bolus acquisition in 76.4% (26/34) and 100% (33/33) of patients, respectively (p = 0.005). Considering extremities with run-off to the ankle and without severe artifact, the concordance rate between low iodine dynamic computed tomography angiography and the routine iodine reference standard was 86.8% (310/357) using fixed delay and 97.9% (425/434) using test bolus (p < 0.001). 4D volume-rendered images using fixed delay and test bolus demonstrated asymmetric flow in 57.7% (15/26) and 58.1% (18/31) (p = 0.978) of patients, and collateral blood flow in 11.5% (3/26) and 22.6% (7/31) of patients (p = 0.319), respectively.

Conclusion

Low iodine dynamic computed tomography angiography with test bolus acquisition has a high concordance with routine peripheral computed tomography angiography performed with standard iodine dose, resulting in improved run-off to the ankle compared to dynamic computed tomography angiography performed after a fixed delay. This method is useful for minimizing iodine dose in patients at risk for contrast-induced nephropathy. 4D volume-rendered computed tomography angiography images provide useful dynamic information.

Keywords

Computed tomography angiography four-dimensional computed tomography blood circulation time peripheral arterial disease atherosclerosis

Introduction

Peripheral artery disease is caused by arteriosclerotic change in the arteries of the lower extremities.¹ The mean incidence of peripheral artery disease and critical limb ischemia is estimated to be 2.35% and 0.35% in the United States, respectively, with more than 200 million individuals estimated to have peripheral artery disease worldwide.² To decide the therapeutic strategy of revascularization, the anatomical classification including the Trans-Atlantic Inter-Society Consensus (TASC) ³ and the angiosome,⁴ an anatomic unit of tissue fed by a source artery, is required.

Traditionally, angiography is the gold standard to assess peripheral artery disease and its severity. CT angiography (CTA) is gradually replacing diagnostic digital subtraction angiography for pretreatment anatomical assessment of peripheral vascular disease because of accuracy, non-invasiveness, and speed⁵ with a pooled sensitivity of 92% and a pooled specificity of 91%.⁶ Over 100 ml of iodine contrast is generally required for clinical routine CTA examination.^7,8 Patients with lower extremity peripheral artery disease often have chronic kidney disease and may undergo repeated intra-arterial procedures, increasing their risk for post-contrast acute kidney injury.⁹,¹⁰ CTA methods that use substantially less iodine are therefore highly desirable in these patients.

Recently, dynamic CTA, which acquires multiple sequential contrast phases after the injection of intravenous contrast, has become available due to the faster CT table speeds and newer image post-processing techniques.¹¹ Its utility, however, has only been investigated in a few studies, with dynamic imaging initiated after either a fixed delay ^12,13 or following test bolus injection.^14,15 For diagnostic low iodine dynamic CTA, accurate delay time after administration of iodine contrast is critical because of the small amount of iodine used; late scanning may lead venous contamination, and early scanning will display non-opacified arteries, which will result in non-diagnostic studies.¹⁶ Low iodine dynamic CTA is performed by estimating when the imaging acquisition can be performed to display the vascular tree. CTA acquisition is therefore performed after either a fixed delay or following a test bolus acquisition. A fixed delay, in which scanning is initiated after a fixed delay time, is easy to implement, with the assumption being that the multiple acquisitions of dynamic CTA will compensate for variable speeds in the runoff of the intravenous contrast. On the other hand, a test bolus acquisition uses a small volume of contrast to estimate when image acquisition will best display the injected contrast.

This study aims to determine if low iodine dynamic CT angiography (CTA) performed after a fixed delay or test bolus acquisition demonstrates high concordance with routine iodine clinical CTA to display lower extremity peripheral arterial disease.

Methods

Patients

This prospective study was approved by our institutional review board, and prior written informed consent was obtained from all patients. Patients who were scheduled for clinical CTA exams of the lower extremities for known or suspected peripheral arterial disease were prospectively enrolled in this study. Exclusion criteria were patients who declined participation, pregnant female patients, and patients whose body weight was more than 109 kg, and estimated glomerular filtration rate less than 60 ml/min/1.73 m². Age, gender, body weight, clinical severity (Fontaine classification), ejection fraction on echocardiogram, ankle-brachial index, and toe-brachial index were abstracted from the electronic medical record. Low iodine dynamic CTA was performed for the first 34 patients using the fixed delay; dynamic CTA was performed following test bolus injection was performed for the next 34 patients. All patients underwent clinical CTA at least 10 min after dynamic CTA.

Dynamic CTA protocol

CT imaging was performed using a 192-slice dual-source CT system (SOMATOM Force, Siemens Healthineers, Forchheim, Germany). Intravenous administration of iodine contrast media was carried out using an automated power injector (Stellant, MEDRAD, PA, USA).

In the dynamic CTA protocol utilizing a fixed delay, a total of 50 ml of iohexol (350 mgI/ml) (Omnipaque 350, GE Healthcare Inc., WI, USA) was intravenously injected at 5 ml/s, followed by 30 ml of saline chaser at 5 ml/s. The dynamic CTA scan started after a 13-s fixed delay after the beginning of intravenous iodinated contrast administration (Figure 1(a)). The fixed delay time was determined based on our clinical experience and was chosen before the arrival of iodine contrast to the femoral artery so that at least one-non-contrast scan could be performed prior to the arrival of intra-arterial contrast in order to enable subtraction of the non-contrast scan, and is similar to prior studies.^12,13

Figure 1.

The schema of dynamic and clinical CTA protocols. Dynamic CTA after a fixed delay protocol (a): A total of 50 ml iodine contrast and saline are intravenously injected and the dynamic CTA scan starts after a 13-s fixed delay after the beginning of intravenous iodinated contrast administration. Dynamic CTA after a test bolus acquisition (b): Monitoring scans are obtained every 2 s at the level of the mid-femoral arteries at 5 s after the beginning of 10 ml of iodine contrast and saline injection. Test bolus monitoring determines when iodinated contrast arrives in the femoral artery. Dynamic CTA images begin to be acquired 4 s prior to the time determined from the test bolus. Dynamic CTA acquisition uses 40 ml of iodinated contrast and saline. Clinical CTA (c): Monitoring scans are performed every 2 s beginning at 10 s after administration of 115 or 145 ml iodine contrast. Clinical CTA with one phase scan starts at a fixed transition delay of 6 s after the CT number at the level of the suprarenal abdominal aorta was 120 HU.

In the dynamic CTA protocol after test bolus acquisition, 10 ml of iohexol (350 mgI/ml) was initially administrated intravenously at 5 ml/s for the test bolus scan, followed by a 10 ml saline chaser. Test bolus images (monitoring images) were obtained at the superior end of the scan range, which was at the level of the mid-femoral arteries. The monitoring image was acquired beginning at 5 s after the initiation of injection, and obtained every 2 s (Figure 1(b)). The test bolus images were loaded into a commercial software on the scanner (DynEva, Siemens Healthineers) to determine the time of arrival of the iodinated contrast media in the femoral artery by the radiologic technologist performing the exam using graphical data. Dynamic CTA images were acquired beginning at 4 s prior to the arrival of intravenous contrast as determined from test bolus monitoring in order for at least one-non-contrast scan to be performed prior to the arrival of intra-arterial contrast (i.e. so subtraction images could be created). For dynamic CTA acquisition, 40 ml of iohexol (350 mgI/ml) contrast was administered at 5 ml/s, followed by 30 ml of saline chaser at 5 ml/s for the dynamic CTA scan, which was initiated based upon test bolus results, as described above. The delay time (i.e. the time between the beginning of intravenous iodine contrast media injection and dynamic CTA acquisition) was recorded for each patient undergoing dynamic CTA after test bolus. The total amount of iodine contrast used for the dynamic CTA using test bolus protocol was consequently identical to that using dynamic CTA with fixed delay, as the amount of contrast injected for dynamic CTA was reduced to account for the 10 ml used for the test bolus (Table 1). However, the examination time of dynamic CTA using test bolus protocol is slightly longer by approximately 10 min than the fixed delay owing to the need for test bolus acquisition.

Table 1.

Total amount of iodine contrast media used for each in scan protocol.

Scan protocol	Total amount of iohexol
Dynamic CTA with fixed delay protocol (n = 34)	Total amount: 50 ml -Dynamic CTA: 50 ml]
Dynamic CTA with test bolus protocol (n = 34)	Total amount 50 ml -Test bolus: 10 ml -Dynamic CTA: 40 ml]
Clinical peripheral CTA (n = 64)	Total amount: 115 ml (body weight:<64 kg; n = 11)Total amount: 145 ml (body weight 64–109 kg; n = 57)]

Dynamic CTA image acquisition was performed the same way for both protocols once scanning was initiated: a total of 11 repeated scans, with the cycle time of 3 s between acquisitions for the first seven scans, and 6 s between acquisitions for the remaining four scans (Figure 1(a) and (b)). The scan range was set at 80 cm proximal to the toes, which extended to the mid femur in every patient. The scan parameters of dynamic CTA were as follows: tube voltage, 70 kV; effective tube current and rotation time product, 125 mAs; collimation, 48 × 1.2 mm; tube rotation time, 0.25 s. The parameters of reconstruction were as follows; slice thickness, 2 mm; increment, 1.2 mm; Kernel: Bv44 (medium sharp vascular kernel); the reconstructed field of view (mm) was individually adapted depending on patient size.

Reference standard routine iodine clinical peripheral CTA

Routine iodine clinical peripheral CTA scans served as the standard reference for low iodine dynamic CTA exams. These reference standard routine iodine CTA exams were performed in spiral CT mode using a routine amount of iodinated contrast, and were obtained following a delay of at least 10 min to permit wash out of intravenous contrast in all patients. Routine iodine reference peripheral CTA exams were performed using 115 or 145 ml of iohexol (350 mgI/mL) using a weight-based table, as follows: for patients <64 kg, 20 ml of iohexol (350 mgI/ml) at 4 ml/s and 95 ml of iohexol (350 mgI/ml) at 3 ml/s, followed by 30 ml of saline chaser at 3 ml/s; for patients 64–109 kg in size, 25 ml of iohexol (350 mgI/ml) at 5 ml/s and 120 ml of iohexol (350 mgI/ml) at 4 ml/s, followed by 30 ml of saline chaser at 4 ml/s (Table 1; Figure 1(c)). The start time of the scan was decided by bolus tracking software (CARE bolus; Siemens Healthineers; Malvern, PA). The monitoring scan was performed at the level of the suprarenal abdominal aorta. Monitoring images were obtained every 2 s starting 10 s after the beginning administration of iodine contrast media. The reference clinical CTA scan started at fixed transition delay of 6 s after the CT number at the level of the suprarenal abdominal aorta reached 120 HU, with images acquired from the top of the liver to the toes (Figure 1(c)). The scan parameters of clinical peripheral CTA were as follows; automatic exposure control and kV selection (CARE kV and CARE Dose 4 D; Siemens Healthineers; Malvern, PA); base protocol quality reference mAs, 180 quality reference mAs at 120 kV; collimation; 192 × 0.6 mm; pitch, 0.4; tube rotation time 0.5 s. The parameters of reconstruction of axial images were as follows; slice thickness, 2 mm; increment 1.2 mm, ADMIRE, 2; Kernel Br44.

Image processing

Assessed images were processed on a workstation (Syngo.via platform, Siemens Healthineers) for the evaluation of peripheral artery disease. Axial, coronal, and sagittal maximum intensity projections were reconstructed. Time-resolved maximum intensity projections, which reflect the maximum densities in every projected slice across all of the acquired phases in dynamic CTA, were processed with and without calcium using a prototype software. 4D volume renderings were created by combining in series 3D volume rendering images at each phase, potentially demonstrating flow dynamics. 4D volume renderings with bones were processed in the anterior and posterior views, and without bones in the posterior view. Dynamic CTA takes approximately 10–15 min longer processing time compared to clinical CTA owing to the large number of phases and images to be processed.

Image quality evaluation

For each dynamic CTA acquisition method, the authors in consensus evaluated if runoff to the ankle was present or not. Additionally, prior to the evaluation of CTA images, a non-reader radiologist with 11 years of experience, who was blind to injection protocol, reviewed image quality for artifacts that might affect interpretation, indicating arterial segments that could not be evaluated due to metallic or motion artifacts.

Concordance of dynamic CTA findings to reference clinical CTA

A radiologist with 25 years of experience in vascular imaging, blinded to acquisition technique, evaluated all low iodine dynamic CTA images for each patient on a workstation (syngo.via platform, Siemens Healthineers). For each lower extremity, the radiologist evaluated seven vascular segments, including the (1) superficial femoral artery, (2) popliteal artery, (3) posterior tibial artery, (4) anterior tibial artery, (5) peroneal artery, (6) dorsalis pedis artery, and (7) plantar arcade, grading luminal narrowing and opacification as “not opacified”, “ <50% stenosis”, “ 50–70% stenosis”, “>70% stenosis”, and “occluded”. In the case of multiple stenoses in an arterial segment, the grade of the worst stenosis was recorded. After evaluation of dynamic CTA images, the same radiologist evaluated all clinical peripheral CTA using axial, coronal, and sagittal plane, maximum intensity projection images along with 3D volume renderings, again grading the most significant stenosis in each vascular segment. Additional information provided by 4D volume rendering images, including the presence of asymmetric blood flow and collateral blood flow, was also assessed.

Statistical analysis

Acquisition methods for dynamic CTA were compared by counting the number of cases showing runoff to the level of the ankle and patient demographic features, including age, gender, body weight, clinical severity, ejection fraction, ankle-brachial index, toe-brachial index, and anatomical distribution of arterial stenosis > 70%. The time that image acquisition started was recorded for test bolus exams. Concordance between dynamic and conventional CTA (i.e. differences in the assignment of the degree of vascular stenosis between dynamic CTA and clinical CTA reference) was achieved when the dynamic CTA demonstrated the identical grade of stenosis. So that timing of acquisition did not affect this estimation, concordance was only evaluated in extremities in which the arterial tree in both legs reached the level of the ankle and were visualized (i.e. after additional exclusion with severe motion or metallic artifacts). A patient could therefore have one extremity that was evaluated in the concordance comparison and one that was not. The number of cases in which 4D volume rendering added significant diagnostic information to conventional clinical CTA was recorded. Each evaluated item was compared between dynamic CTA following fixed delay acquisition and dynamic CTA following test bolus acquisition using the t-test for ratio scale, Wilcoxon rank sum test for ordinal scale, Chi-square test or Fisher exact test for nominal scale, as appropriate, with a p value less than 0.05 was considered statistically significant. Statistics were performed with JMP Pro (version 14.1.0, Statistical Discovery from SAS, NC, USA).

Results

A total 68 patients (average age; 66.1 ± 12.3 years, male: female = 49: 19) were consecutively enrolled between August 2017 and March 2019. The first 34 patients (average age; 63.9 ± 13.4 years, body weight; 92.6 ± 17.3 kg, male: female = 21: 13) were examined using dynamic CTA acquisition after a fixed delay of 13 s, and the next 34 patients (average age; 68.3 ± 10.8 years, body weight; 108.4 ± 155.1 kg, male: female = 28: 6) underwent dynamic CTA after test bolus acquisition. The CT dose volume index, a measure of scanner radiation output was 19.3 mGy (a fixed value for every patient) for dynamic CTA scans and 6.3 ± 3.0 mGy for routine iodine clinical reference CTA.

Table 2 shows patient clinical characteristics for patients undergoing low iodine dynamic CTA following fixed delay or test bolus acquisition. The mean ankle-brachial index was 0.77 ± 0.22 vs. 0.60 ± 0.32 (p = 0.005), for the fixed delay vs. test bolus technique, respectively, indicating potentially greater PAD burden in the test bolus arm. Other clinical characteristics were distributed similarly between the two tests.

Table 2.

Patient clinical characteristics in each arm of the low iodine dynamic CTA study.

	Fixed delay (SD)	Test bolus (SD)	p value
Patient level
Age (year)	63.9 (13.4)	68.3 (10.6)	0.14
Number of Females	13	6	0.94
Body weight (kg)	82.6 (17.3)	108.4 (155.1)	0.35

Fontaine classification
1	12	11	0.35
2	17	14
3	5	4
4	0	5
Ejection fraction (%)	59.6 (10.9)	56.5 (6.9)	0.26
Extremity level
Ankle brachial index	0.77 (0.22)	0.60 (0.32)	<0.05*
Toe brachial index	0.48 (0.24)	0.41 (0.26)	0.15
Stenosis (>70%) distribution
Thigh - knee	14	18	0.32
Lower leg	18	20	0.47
Foot	16	21	0.15

*p < 0.05.

Note: There are 34 patients in each arm, except for ejection fraction (with echocardiography performed in 22 and 24 patients using fixed delay vs. test bolus acquisition, respectively) and ankle-brachial and toe-brachial index (available 23 and 28 patients undergoing fixed delay vs. test bolus acquisition, respectively). Values shown as mean (standard deviation). For severe stenoses, a patient was counted as positive if any vessel had more than 70% stenosis at the named anatomic level.

Test bolus acquisition was successful in 33/34 patients. One patient was a technical failure owing to heavily calcified femoral arteries, as the CT number in the femoral arteries did not change after the test bolus injection, and the subsequent dynamic CTA acquisition was cancelled. In patients undergoing dynamic CTA after test bolus, the mean delay prior to image acquisition was 19.5 s (median; 20 s, range; 8 ̶ 32 s), with 84.3% (27/32) of patients having a delay of 13 s or more (Figure 2). Run-off to the level of the ankle was observed in 100% (33/33) of patients using dynamic CTA following test bolus acquisition, compared to 76.4% (26/34) of patients undergoing dynamic CTA with fixed bolus technique (p = 0.005) (Figures 3 and 4) despite a smaller amount of intravenous contrast being used for dynamic CTA (because 10 ml of contrast was required for test bolus acquisition).

Figure 2.

Dynamic CTA exams performed after test bolus demonstrated a wide range in delay times prior to CTA acquisition (mean; 19.5 s, median; 20 s, range; 8–32 s).

Figure 3.

Dynamic CTA performed after test bolus injection with 40 ml of contrast demonstrating run-off to the ankle in a 37-year-old with risk factors including smoking and hyperlipidemia. Time-resolved maximum intensity projections image demonstrates whole lower extremities anatomy (a). Serial 4D volume rendering images from dynamic CTA after test bolus acquisition show contrast media reaches to the proximal superficial femoral artery at the 4th phase (b-1) and run-off to the level of the ankle at 9th phase (b-6).

Figure 4.

Dynamic CTA performed using fixed delay protocol with 50 ml of contrast demonstrating run-off to the knee in an 88-year-old with the left popliteal aneurysm. Contrast media reached to the knee but not ankle on time-resolved maximum intensity with (a) and without calcium (b). The aneurysm is seen in the left popliteal artery (a, b: arrow).

Figure 5 shows the number of patients who underwent concordance analysis between low iodine dynamic CTA and reference standard routine iodine peripheral CTA. Only patients with runoff to the level of the ankle but without severe motion or metallic artifact precluding image evaluation were included in this comparison, as we intended to compare low iodine acquisition techniques and not patient groups. For the concordance comparison between dynamic CTA and conventional CTA, 357 arterial segments in 26 patients (51 extremities) were included in the fixed delay group, and 434 arterial segments in 31 patients (62 extremities) were included in the test bolus group.

Figure 5.

The number of patients who underwent concordance analysis between low iodine dynamic CTA and reference standard clinical CTA using routine iodine dose.

The concordance between the degree of stenosis for all arterial segments between dynamic CTA using a fixed delay and the clinical reference CTA was 86.8% (310/357) versus 97.9% (425/434) concordance with dynamic CTA using test bolus (p < 0.001). This difference in concordance was greater below the ankle (68.6% [70/102] with fixed delay vs. 94.4% [117/124] with test bolus, p < 0.001, Figure 6) compared to above the ankle (94.1% [240/255] with fixed delay vs. 99.4% [308/310] with test bolus, p < 0.001).

Figure 6.

Bar graph of maximum luminal stenosis per arterial segment for low iodine dynamic CTA and routine iodine, clinical reference routine peripheral CTA using dynamic CTA obtained after fixed delay (a) and after test bolus acquisition (b).

4D volume renderings demonstrated asymmetric flow in 57.7% (15/26) of patients undergoing dynamic CTA with fixed delay and in 58.1% (18/31) of patients undergoing dynamic CTA with test bolus (p = 0.978) (Figure 7). 4D volume renderings demonstrated blood supply from collateral circulation in 11.5% (3/26) of patients undergoing fixed delay dynamic CTA and in 22.6% (7/31) of patients undergoing dynamic CTA with test bolus (p = 0.319) (Figure 8).

Figure 7.

A 62-year-old male with right femoral endarterectomy with common and external iliac stenting for right leg claudication. Volume rendering on clinical CTA demonstrates symmetric vascular anatomy (a). 4D volume rendering corresponding to the 7th phase from dynamic CTA with test bolus showing unopacified arteries of the left lower extremity (b). The time-resolved maximum intensity projection without calcium demonstrates distal runoff (c). These findings indicate asymmetric blood flow.

Figure 8.

A 69-year-old female who presented with left lower extremity claudication and left groin pain demonstrates blood supply from collateral circulation. The corkscrew-like artery is demonstrated on the left thigh on time-resolved maximum intensity projection image (a: arrow). 4D volume rendering reveals the corkscrew-like artery supplies blood flow to the distal left lower extremity at the same speed as the right side (b: arrows). VR: volume rendering.

Discussion

Because patients with peripheral arterial disease often have chronic kidney disease or intra-arterial procedures, using a large amount of iodinated contrast media for CTA assessment may place them at increased risk of further renal impairment. Therefore, this study investigated low iodine dynamic CTA for assessment of peripheral arterial disease with image acquisition initiated after either a fixed delay or after test bolus acquisition, using routine iodine clinical CTA as the standard reference. The low iodine dynamic CTA protocol utilized about 34.5% of our standard intravenous iodine dose for patients 64–109 kg in size. Reducing the iodine load for CTA may be especially important to patients with lower extremity peripheral artery disease who suffer from chronic kidney disease.¹⁰ Importantly, complete opacification of vascular tree occurred more often when a test bolus was employed (100% vs. 76.4%, p = 0.005) despite the fact that the ankle-brachial index in test bolus arm was significantly worse than in the fixed delay arm. Additionally, even considering only extremities with a run-off to the ankle, the concordance of the degree of stenosis for each segment was higher in the test bolus group (97.9%) than that in the fixed delay group (86.8%; p < 0.001).

A few prior studies have examined low iodine dynamic CTA in lower extremities employing a fixed delay protocol,^12,13 while others have examined dynamic CTA using a test bolus protocol.^14,15 However, no prior work compares these two acquisition methods. Therefore, we initially performed dynamic CTA using a fixed delay protocol to determine the need for individualization of variable delays, as the dynamic CTA technique performs 11 volume acquisitions, and a fixed delay would be clinically efficient; however, a substantial number of cases demonstrated that acquisition must have been initiated too early as run-off to the ankle was not achieved. The patient results from dynamic CTA after test bolus showed a wide range of delay times (8–32 s), with 84.3% patients having a delay of 13 s or greater. These findings are consistent with a recent study demonstrating that individualized delays for abdominal CTA are substantially longer than generally thought, even when using bolus tracking with a fixed transition delay, and that optimizing CTA acquisition can result in diagnostic studies with less iodine injected at a slower rate.¹⁷ The arterial blood flow to lower extremities is influenced by underlying vascular disease and an individual’s cardiovascular status, and these factors may be amplified in the lower extremities compared to the abdominal region. The monitoring scans obtained in test bolus protocol take additional examination time (approximately 5–10 min) compared to fixed delay protocol; however, the test bolus protocol can provide individual adaptation for impaired cardiac status or upstream atherosclerosis, which is not available using a fixed delay, and which may be risky in the femoral arteries using bolus tracking. Technical failure of the test bolus technique occurred in one patient due to dense, confluent femoral artery calcifications; if this occurred in clinical practice, a subsequent low iodine dynamic CTA with fixed delay could be performed.

The concordance rate for the degree of stenosis for each segment between dynamic CTA following test bolus and clinical CTA (97.9%) and significantly higher than that in the fixed delay group although it was compared after exclusion cases without run-off to the ankle. Much of this improvement using test bolus protocol likely resulted from opacification in the arteries of the foot, including the dorsalis pedis and plantar arcade artery. Low iodine dynamic CTA using test bolus should be considered as an alternative to clinical peripheral CTA when providers need to image lower extremity peripheral arterial disease but they or their patients are reticent to undergo standard CTA exam due to the higher iodine load out of concerns for contrast-induced nephropathy. There is a slight radiation penalty associated with the multiple low dose acquisitions of required for dynamic CTA, but the radiation scanner output is similar to routine abdominopelvic CT exams. Post-processing and interpretation time is also longer in dynamic CTA because of multiple phases of image acquisition and dynamic flow information. Dynamic CTA is available with CT systems from multiple vendors but requires fast table speeds or wide volume detectors.

Dynamic CTA can provide flow dynamics information.¹⁸ 4D volume rendering image offered additional information on arterial flow dynamics like digital subtraction angiography and could reveal asymmetric and collateral blood flow.

There were limitations in this study. First, we excluded patients with estimated glomerular filtration less than 60 ml/min/1.73 m², even though these patients would be those that would benefit from a low iodine CTA exam. Our rationale was that our study required back-to-back low iodine CTA and clinical CTA exams. The total iodine limit was well within that set at our institution for patients receiving iodinated contrast; however, we did not want to administer this amount to patients with evidence of renal impairment.⁹ Second, clinical CTA was used as the standard reference instead of digital subtraction angiography because the current CTA could replace it. Third, dynamic CTA using fixed delay to compare with that with test bolus was performed in different groups of patients due to the desire to minimize radiation and iodine dose. Forth, we utilized only a single vascular radiologist for each portion of the study and did not examine inter-observer agreement as our purpose was to compare the efficacy of the two dynamic CTA techniques rather than deriving a performance estimate of accuracy. The vascular radiologist assessing for concordance always examined dynamic CTA images first, potentially leading to bias. Therefore, concordance estimates in this study should not be viewed as performance estimates for this new CTA technique. Readers should be aware that the craniocaudal distance of dynamic CTA scanning is constrained by the table speed, length of the CT detector, and the number of acquisitions required for this scanning mode (from the mid-femoral arteries to the toes in our study), and dynamic CTA is available on not only premium CT systems but also a broad range of single- and dual-source CT systems.

Although this study enrolled patients with known or suspected lower peripheral arterial disease, dynamic CTA using a routine amount of contrast can provide important diagnostic information in other vascular diseases where imaging over time may add additional important diagnostic information: for example, dynamic CTA has been shown to provide additional information such as dynamic ejection of contrast into the false lumen, and dynamic obstruction of the left renal artery and dynamic change in renal perfusion, compared to standard CTA, in patients with aortic dissection.¹⁹ Dynamic CTA has also been shown to be useful in the evaluation of endoleaks after endovascular aortic aneurysm repair, where endoleaks may demonstrate enhancement later than that observed with conventional CTA.²⁰ Further investigation is of low iodine technique coupled with dynamic CTA may be warranted for these diagnostic tasks, when clinically indicated.

Conclusion

Dynamic CTA following test bolus acquisition using a small amount of iodine contrast media results in high concordance with clinical CTA, and improves run-off to the ankles compared to a fixed delay protocol. Dynamic CTA can also provide additional diagnostic information, including asymmetric flow using 4D volume renderings, in a substantial proportion of patients with suspected peripheral arterial disease.

Footnotes

Acknowledgements

The authors acknowledge the assistance of Sonia Watson, PhD, in editing the manuscript, and Taylor Moen for assisting the radiologists during interpretation sessions. This study was approved by the Mayo Clinic Institutional Review Board. This paper was presented at 105^th Radiological Society of North America (Chicago, IL, U.S.A.) between from Dec/1/2019 to Dec/6/2019.

Declaration of conflicting interests

The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Ahmed Halaweish, PhD and Irene Dube were employees of Siemens AG at the time the study was completed. Cynthia H. McCollough is supported by an industry grant from Siemens AG. Shuai Leng has a license agreement with Bayer AG. Joel G. Fletcher is supported by industry grants from Siemens AG and Takeda Pharmaceutical Ltd, and a consultant of Medtronic. The other authors have no conflicts of interest to declare.

Funding

The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Funding was provided by Mayo Clinic and Siemens AG.

ORCID iDs

Akitoshi Inoue

Joel G Fletcher

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