Spiral laminar flow in the abdominal aorta: a predictor of renal impairment deterioration in patients with renal artery stenosis?

J. Graeme Houston1,2, Stephen J. Gandy1, Wendy Milne1, John B. C. Dick, Jill J. F. Belch2 and Peter A. Stonebridge2

1 Tayside University Hospitals, Clinical Radiology, Dundee, UK and 2 Tayside University Hospitals, Tayside Institute for Cardiovascular Research, Dundee, UK

Correspondence and offprint requests to: J. G. Houston, Tayside University Hospitals, Clinical Radiology, Ninewells Hospital, Dundee DD1 9SY, UK. Email: graeme.houston{at}tuht.scot.nhs.uk



   Abstract
 Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 References
 
Background. Spiral or helical arterial blood flow patterns have been widely observed in both animals and humans. The absence of spiral flow has been associated with carotid arterial disease. The aim of this study was to detect the presence of aortic spiral flow using magnetic resonance imaging (MRI) and to evaluate the relationship of the presence of spiral aortic flow with renal arterial disease and renal function in the follow-up of patients with suspected renal atheromatous disease.

Methods. Prospective study of 100 patients with suspected renal arterial disease and 44 patient controls. Using a 1.5T MRI unit (Siemens Symphony), phase contrast flow quantification and three-dimensional contrast enhanced MR angiography of the abdominal aorta were performed. Renal arterial stenoses (RAS) were classified minimal, moderate or severe. Renal function was followed at 3 months before and 6 months after MRI.

Results. Non-spiral flow was more prevalent in patients with more severe RAS. Renal impairment progressed significantly in severe RAS without spiral flow (P = 0.0065), but did not progress significantly in severe RAS with spiral flow (P = 0.12). In minimal or moderate RAS with or without spiral flow there was no significant progression (P = 0.16, 0.13, 0.47, 0.092, respectively).

Conclusions. Aortic spiral blood flow can be assessed with MRI. Lack of aortic spiral blood flow in patients with severe RAS is associated with significant short-term renal function deterioration. Determination of blood flow patterns may be a useful indicator of renal impairment progression in patients with suspected renal artery stenosis.

Keywords: aorta; artery; flow; function; MRI; stenosis



   Introduction
 Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 References
 
Atheromatous renal vascular disease (ARVD) is a common cause of chronic renal failure (CRF) and end-stage renal failure (ESRF) [1]. More than 15% of all patients with ESRF have ARVD. The prevalence of ARVD approaches 25% in the elderly dialysis population [2]. Endovascular renal artery angioplasty, stent replacement and renal artery reconstruction are recognized methods of treating renal artery stenosis [3]. This intervention is based on the significant progression of renal artery stenosis to occlusion with subsequent loss of function [4]. It would be of great clinical value to be able to predict those patients with severe renal artery stenosis most likely to progress and perhaps therefore most likely to benefit from intervention.

MR angiography (MRA) is acceptably accurate as a non-invasive investigation for ARVD in both hypertensive and CRF patients. It has the potential of providing functional information by way of dynamic perfusion imaging as well as providing accurate angiographic information [5,6].

A greater understanding of the blood flow patterns in arterial disease is being achieved with the use of non-invasive imaging. While trans-oesophageal ultrasound has been used to assess blood flow patterns in the ascending and descending arch [7], magnetic resonance imaging (MRI) is well tolerated and allows a number of velocity mapping methods to be employed. Two-dimensional velocity maps can be displayed as vector maps in the vessels or heart [8,9]. Vector mapping has been used in the normal aorta [10], in aortic coarctation [8] and in aneurysms and grafts [11]. The numbers of subjects in these studies has been small and the time of acquisition prolonged.

A spiral or helical blood flow pattern has been widely observed in arteries in both the animal and the human. Ultrasound has been used in the assessment of the aorta in dogs [12] and in the femoral arteries in humans [13], while MRI has been used in humans in the aortic arch [8,10]. In this observed flow pattern in addition to the laminar flow in the direction of the artery, there is a rotation in the plane of the cross-section of the artery (spiral laminar flow). In this study we have adapted a previously reported two-dimensional flow quantitative technique in the aortic arch, as a means of determining rotational or spiral flow patterns in the abdominal aorta [14]. The advantages of the technique were that volume flow rather than particle flow was determined and mean magnitude of vector velocities transverse to the direction of blood flow in the arch could be quantified for different positions in the arch at different times in the cardiac cycle to allow determination of a spiral flow pattern.

The aim of this study was to evaluate the relationship between the observed spiral laminar flow pattern in the abdominal aorta and severity of renal arterial stenosis (RAS) and renal function deterioration up to 6 months after initial MRI assessment.



   Subjects and methods
 Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 References
 
Patients
100 patients with suspected renal arterial atheromatous disease on clinical criteria of coexistent vascular disease, presenting with renal impairment (86%), hypertension (25%) and diabetes mellitus (32%) and 44 patients controls with hypertension and no renal impairment or renal artery stenosis were enrolled. Patients older than 90 years, claustrophobic or those unable to achieve reliable ECG gate and acceptable breath hold for MRI angiography were excluded. The study complied with the local ethical committee approval.

MRI
All examinations were performed on a 1.5T Siemens (Erlangen, Germany) Symphony MRI Unit using phased array torso coil and Medrad Spectris II contrast injector. Siemens Numaris 3 software was employed for post-processing image analysis (version 3833D, Erlangen, Germany).

The 3D contrast enhanced MR angiogram was performed using a coronal oblique orientation through the upper abdominal aorta to include kidneys with TR 4.0 ms, TE 1.65 ms, flip angle 25°, matrix 256 x 160, one acquisition, field of view (FOV) 350–430 mm, effective slice thickness 1–1.2 mm, 0.15 mmol/kg gadolinium (Magnevist, Schering Health Care). The blood flow pattern assessment was performed using a two-dimensional velocity encoded phase contrast sequence using a coronal oblique orientation through the upper abdominal aorta. The position of this plane was carefully determined aligned with the middle longitudinal plane of the aorta in the supra-renal aorta. The sequence parameters were TR 46 ms, TE 11 ms, flip angle 30°, matrix 256 x 512, number of excitations (NEX) one, FOV 370–450 mm, slice 6 mm, number of slices 8–12, acquisition window > 75% of R-R interval, velocity encoding of 20 cm/s, time of acquisition 5–7 min. The ECG trigger was set with no delay from the R-R interval, and a minimum of eight phases.

MR angiogram analysis
The contrast enhanced MR angiogram was evaluated by a radiologist blinded to the renal function and blood flow pattern analysis, using maximum intensity projections, double oblique multiple plane reformat and evaluation of source images, for assessment of RAS. The main aortic diameter at the level of the right renal artery was measured in millilitres. Renal stenoses were determined as percentage narrowings over distal patent renal arterial diameter. These were classified as unilateral or bilateral, minimal (< 30% stenosis), moderate (30–60% stenosis) or severe (> 60%) stenoses.

Blood flow pattern analysis
The velocity encoded phase datasets were evaluated by a radiologist blinded to the MRA and renal function analysis. In a similar technique to that reported for the detection of spiral flow in the aortic arch [14], using standard flow quantification software, a standard 4–5 mm circular region of interest (ROI) was placed on the outer third of the aorta on either side (right and left) of the mid-aortic part point, 5–10 cm above (supra-renal) the right renal artery, on the coronal oblique late diastolic source image. The flow quantification graphs produced displayed the time resolved prospective gated mean velocity in cm–1 within each ROI (Figure 1). Evaluation of the velocity encoded phase time resolved images in both static or cine review in early to mid-diastole (250–450 ms) was performed. A rotational or spiral blood flow pattern was determined if the direction of flow of the transverse velocity vector, comparing the right and left regions of interest, were opposite and the magnitude of the velocity vector was > 2 cm–1. A magnitude < 2 cm–1 was considered too small to be significant due to error estimation in the velocity measurement. The source time resolved images were viewed in a cineloop to compare the directional information with the graphical representation for internal correlation. If discordance was observed further ROIs were selected until concordance was achieved.






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Fig. 1. (a) 3 dimensional contrast enhanced MRA of renal arteries of a patient shows minimal stenoses of both renal arteries. (b) Phase contrast source image shows positions of ROIs for flow quantification, (c) right and (d) left flow quantification shows mean velocities in the opposite directions indicating spiral flow.

 
Follow-up
Renal function was followed at 3 monthly intervals from 3 months pre- and 6 months post-MRI by serum creatinine determination. The presence or absence of spiral blood flow in the abdominal aorta was determined and compared with the severity of renal artery stenosis and presence of renal function deterioration at 9 months follow-up.

Statistics
Subject data was divided into normal subjects, minimal, moderate or severe RAS. Comparison of datasets was between subject groups, degrees of renal artery stenosis, serum creatinine and presence or absence of supra-renal spiral aortic flow. Statistical comparisons were made using a standard one-sided two-sample t-test. The test for equality or inequality of the variance of each group was determined using a two-sample F-test, with a cut off of P<0.05 for inequality. Due to the small sample sizes further statistical assessment was not performed.



   Results
 Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 References
 
Ninety-one patients and 44 controls gave acceptable, interpretable MR angiograms, ECG gated results and completed renal function follow-up to a minimum of 9 months. Of the nine patients who did not complete the study, four were lost to follow-up and five died, three due to myocardial infarction, and two from stroke. All the patients tolerated the examination with minimal discomfort. The MRI technique was well tolerated and could be added to the standard MRA examination without prolonging the study for > 10 min. While the geometry of the aorta did not allow data acquisition in the whole infra-renal aorta in all patients, acceptable rates of data acquisition were achieved for the aorta in the supra-renal position in all patients.

The patient demography and numbers by severity of RAS is described in Table 1. There was a preponderance of males, and the patients with moderate or severe RAS tended to be older, although the mean ages of each group were comparable. The numbers of patients in the moderate RAS group was small. In the moderate RAS group, two of 14 patients had bilateral RAS, both moderate stenoses. In the severe RAS group, 34 of 45 (75%) patients had bilateral RAS, the contralateral kidney RAS was moderate in 16 patients and severe in 18 patients.


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Table 1. Distribution of patients by severity of renal artery stenosis

 
Flow patterns observed
The prevalence of spiral laminar flow in the supra-renal aorta in controls, minimal, moderate and severe RAS was 66, 62, 36 and 29%, respectively. There is a trend to reduced prevalence in more severe RAS. An example of contrast enhanced MRA and corresponding flow quantitative two-dimensional MRI images are shown in Figure 1.

Renal function follow-up
The results include those patients that completed the short follow-up period of a minimum of 9 months; 3 months pre-MRA (Early) and 6 months post-MRA (Late) in 91 patients and 44 controls. The results are summarized in Figure 2. There was a trend to renal function deterioration in the patient group but not the controls. Significant deterioration in renal function occurred in the severe RAS (t-test, P = 0.0043) and not significant for moderate, minimal RAS or controls (t-test, P = 0.51, 0.21, 0.51). The mean renal function follow-up for all patients in the supra-renal aortic position showed that for those with spiral flow present, the mean serum creatinine rose from 133 (SD 43) to 145 (SD 75) µmol/l, which was not statistically significant (P = 0.082) whereas for those with non-spiral flow the serum creatinine rose from 163 (SD 67) to 191 (SD 101) µmol/l, which was statistically significant (P = 0.0058). The baseline serum creatinine was higher for non-spiral flow patients. There is a trend for renal impairment progression in both groups, more marked for non-spiral flow patients. This difference clearly could have been due to the strong association of lack of spiral flow with RAS severity. To evaluate this effect the follow-up data were analysed by RAS severity according to the presence or absence of spiral flow.



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Fig. 2. Renal function follow-up by severity renal artery stenosis.

 
The renal function follow-up is described by spiral flow presence and RAS severity in Figure 3. The trend of renal impairment progression remains more marked for non-spiral flow patients than for spiral flow patients. Overall, even in this small group of patients, the presence of spiral flow was associated with a trend of less severe progression compared with those patients with no spiral flow. Spiral flow patients in the minimal, moderate and severe RAS groups showed no significant difference in serum creatinine (P = 0.16, 0.13, 0.12, respectively). Non-spiral flow patients in the minimal, and moderate RAS groups showed no significant difference in serum creatinine (P = 0.47, 0.92, respectively). Non-spiral flow patients with severe RAS showed significant progression in renal impairment (P = 0.0066). Allowing for RAS severity the progression of renal impairment was associated with a lack of aortic spiral flow.



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Fig. 3. Renal function follow-up by severity RAS and spiral flow in spiral flow (S.F.) and non-spiral flow (Non S.F.).

 


   Discussion
 Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 References
 
This study demonstrates that spiral flow, while reported previously as a normal finding, is not present in all patients and is more frequently absent in patients with increasing severity of renal artery stenosis and those with more rapid deterioration of renal function. While this has been suggested to be due to loss of arterial elasticity or compliance [15], the relevance of spiral blood flow patterns to atheromatous disease merits further consideration.

There is evidence that blood flow patterns of haemodynamics is directly involved in atherosclerosis. Turbulent flow induces a complex process that promotes atherogenesis by enhancing its three phases of development [16]. In the first phase, the vascular endothelium is damaged, exposing the subendothelial surface to circulating blood. Platelet aggregation and adhesion occur with subsequent microthrombi formation over the micro-fissures induced by the abnormal shear stresses and turbulent flow [17]. The second phase is inflammatory, caused in part by the release of growth factors that induce smooth muscle cell proliferation and stenoses. Lipid accumulation is mediated through abnormal macrophage behaviour and changes in local lipid metabolism, e.g. in sterol regulatory element-binding proteins, which increase the mRNA encoding of the low-density lipoprotein (LDL) receptor and therefore the binding of LDL. Thus, both vascular stenoses and lipid-laden plaque formation are promoted. The third phase, that of abnormal adaptive vascular remodelling is also enhanced, as the shear stresses and turbulent flow increase. All of these processes, occurring as a result of the abnormal vascular shear stresses, increase atherogenesis.

Previous work using a similar MRI technique has shown that aortic arch spiral flow is prevalent in normal individuals and the there is a reduced prevalence of aortic arch spiral flow in those patients with carotid artery atheromatous disease [14]. While it is not clear if the lack of spiral flow is a result of loss of vascular compliance, early work on flow rig using MRI has demonstrated that spiral flow stabilizes flow through stenoses by reducing turbulence compared with non-spiral flow [18]. In addition, atheromatous disease is associated with areas of low wall shear stress [19]. As wall shear stress is related to the velocity of fluid adjacent to the wall, the combination of a rotational velocity vector with the axial velocity would be expected to increase the wall shear stress. We hypothesize that spiral flow may increase the wall shear stress so reducing the stimulus for atherogenesis. This work supports this hypothesis. Further work is required to evaluate the effects of different flow patterns on wall stresses in vivo.

As this study was a prospective evaluation of consecutive patients with suspected RAS due to clinical presence of vascular disease at other sites, and renal impairment, no attempt has been made to control for medication or match for age, sex or baseline renal function between groups. A control group of patients with hypertension but no renal impairment and normal renal MRA was included. Clearly further study with matching within groups and follow-up MRA evaluation would be required. While this preliminary study used serum creatinine as the measure of renal function parameter, in further studies creatinine clearance and assessment of renal blood flow should be included.

The determination of spiral blood flow patterns in clinical practice may be of more interest than allowing possible explanation of factors affecting renal impairment progression or atheroma progression. The techniques described, when used in appropriate context may allow prediction of disease progression in certain patient groups. Previous work by Harden et al. demonstrated that renal artery stent placement could delay or alleviate the decline in renal function displayed by the inverse creatinine plot [20]. The ability to predict this decline from a single examination time-point would be clinically valuable to guide those most suitable for renal artery stent placement. Moreover, given the small but significant morbidity, cost and recurrence rate in such intervention, the addition of further non-invasive methods of determining those patients most suitable for intervention would be expected to be of both clinical value and be cost effective.

In conclusion, aortic spiral blood flow can be assessed in patients being investigated for renal arterial disease with MRI. Lack of aortic spiral blood flow in patients with RAS is associated with significant short-term renal function deterioration in patients with >60% renal artery stenosis. Following further study, lack of aortic spiral blood flow may prove a useful poor prognostic indicator and may have a role in determining those patients most suitable for renal re-vascularization.



   Acknowledgments
 
We are grateful for the assistance from the MRI technical staff of Tayside University Hospitals.

Conflict of interest statement. Two authors are shareholders in Tayside Flow Technologies Ltd, a medical devices company developing vascular grafts and stents. The other authors have no conflict of interest to disclose.



   References
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 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 References
 

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Received for publication: 4.12.03
Accepted in revised form: 25. 2.04