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DOI:10.2214/AJR.06.0584
AJR 2007; 188:W334-W340
© American Roentgen Ray Society


Pictorial Essay

MR Angiography for Patient Surveillance After Endovascular Repair of Abdominal Aortic Aneurysms

Ryan B. Schwope1, Huntley J. Alper, Adam D. Talenfeld, Emil I. Cohen and Robert A. Lookstein

1 All authors: Department of Interventional Radiology, Mount Sinai Medical Center, One Gustave L. Levy Pl., Box 1234, New York, NY 10029.

Received April 29, 2006; accepted after revision August 1, 2006.

 
Address correspondence to R. A. Lookstein (robert.lookstein{at}msnyuhealth.org).

WEB This is a Web exclusive article.


Abstract
Top
Abstract
Introduction
Abdominal Aortic Endografts
Postoperative Complications
MR Protocol and Technique
Imaging Characteristics in the...
Summary
References
 
OBJECTIVE. The objective of this article is to demonstrate how new imaging sequences and techniques allow characterization of postoperative complications after endovascular surgery and offer the physician more information for planning treatment than ever before.

CONCLUSION. MR angiography is an excellent technique for the surveillance of patients after endovascular repair of abdominal aortic aneurysms because it is highly sensitive for the detection of postoperative complications. A thorough knowledge of the physical properties of the endovascular components is essential to choose the appropriate patients for this form of surveillance.

Keywords: abdominal aortic aneurysms • dynamic MRI • MDCT • MR angiography • MRI • vascular stents


Introduction
Top
Abstract
Introduction
Abdominal Aortic Endografts
Postoperative Complications
MR Protocol and Technique
Imaging Characteristics in the...
Summary
References
 
Since first described in 1991 [1], endovascular aneurysm repair has become increasingly used for the treatment of abdominal aortic aneurysms. Lifelong surveillance of aortic endografts is imperative because postoperative complications, including endoleaks, endotension, limb occlusion, and device migration, are not rare. MDCT angiography (MDCTA) is currently the standard in many institutions for postoperative surveillance. A technique using MRI and MR angiography (MRI/MRA) offers an excellent alternative to MDCTA for patient surveillance after endovascular aneurysm repair [2]. This technique is most useful in patients with nickel-titanium (nitinol)-based devices because this type of endograft is clearly visualized with little or no artifact [3].

Stainless steel devices produce significant metallic artifact, limiting evaluation, and are not suited for postoperative surveillance with MRI. New MR pulse sequences, including "white blood" imaging and time-resolved imaging, allow assessment of the aneurysm sac with improved ability to characterize endoleaks and endotension [4-6]. MRI/MRA is ideal for patients with renal insufficiency and does not use ionizing radiation. Contrast-enhanced MR angiography offers excellent sensitivity for the detection of endoleaks and has been shown in previous reports to be more sensitive than MDCTA [2, 6].


Abdominal Aortic Endografts
Top
Abstract
Introduction
Abdominal Aortic Endografts
Postoperative Complications
MR Protocol and Technique
Imaging Characteristics in the...
Summary
References
 
Several endografts are currently available for endovascular repair. At present, only nitinol-based devices are approved for MRI/MRA [3]. The safety of stainless steel endografts and their use with MRI/MRA has not been established. The AneuRx endograft (Medtronic Medical), the Gore Excluder abdominal aortic device (Gore Medical), and the Endologix endovascular graft (Endologix) are currently approved by the U. S. Food and Drug Administration (FDA) for endovascular aneurysm repair (Figs. 1A, 1B, 1C and 2A, 2B, 2C). All three devices are composed of a nitinol skeleton and therefore create minimal metallic artifact. The Medtronic Talent (Medtronic Medical) device is FDA-approved for investigational use only (Fig. 3A, 3B, 3C) and is also composed of nitinol, making it MRI/MRA compatible. The Zenith endovascular graft (Cook Medical) is FDA-approved for endovascular aneurysm repair; however, due to the stainless steel skeleton, this device is not approved for use with MRI/MRA.


Figure 1
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Fig. 1A —AneuRx (Medtronic Medical) endovascular device designed to treat infrarenal abdominal aortic aneurysms. Photograph (courtesy of Medtronic Vascular, Santa Rosa, CA) (A), radiograph (B), and coronal maximal-intensity-projection image from contrast-enhanced MR angiography (C). Modular, self-expanding endovascular device designed to treat infrarenal abdominal aortic aneurysms. This stent-graft module consists of smooth woven polyester graft that is joined to nitinol exoskeleton.

 

Figure 2
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Fig. 1B —AneuRx (Medtronic Medical) endovascular device designed to treat infrarenal abdominal aortic aneurysms. Photograph (courtesy of Medtronic Vascular, Santa Rosa, CA) (A), radiograph (B), and coronal maximal-intensity-projection image from contrast-enhanced MR angiography (C). Modular, self-expanding endovascular device designed to treat infrarenal abdominal aortic aneurysms. This stent-graft module consists of smooth woven polyester graft that is joined to nitinol exoskeleton.

 

Figure 3
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Fig. 1C —AneuRx (Medtronic Medical) endovascular device designed to treat infrarenal abdominal aortic aneurysms. Photograph (courtesy of Medtronic Vascular, Santa Rosa, CA) (A), radiograph (B), and coronal maximal-intensity-projection image from contrast-enhanced MR angiography (C). Modular, self-expanding endovascular device designed to treat infrarenal abdominal aortic aneurysms. This stent-graft module consists of smooth woven polyester graft that is joined to nitinol exoskeleton.

 

Figure 4
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Fig. 2A —Gore Excluder (Gore Medical) abdominal aortic device. Photograph (courtesy of Gore Medical) (A), radiograph (B), and coronal maximal-intensity-projection image from contrast-enhanced MR angiography (C). Abdominal aortic device is modular bifurcated endovascular system. Skeleton is made of nitinol, which spans length of each component. Polytetrafluoroethylene (PTFE) graft material is attached to nitinol with polyethylene tape.

 

Figure 5
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Fig. 2B —Gore Excluder (Gore Medical) abdominal aortic device. Photograph (courtesy of Gore Medical) (A), radiograph (B), and coronal maximal-intensity-projection image from contrast-enhanced MR angiography (C). Abdominal aortic device is modular bifurcated endovascular system. Skeleton is made of nitinol, which spans length of each component. Polytetrafluoroethylene (PTFE) graft material is attached to nitinol with polyethylene tape.

 

Figure 6
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Fig. 2C —Gore Excluder (Gore Medical) abdominal aortic device. Photograph (courtesy of Gore Medical) (A), radiograph (B), and coronal maximal-intensity-projection image from contrast-enhanced MR angiography (C). Abdominal aortic device is modular bifurcated endovascular system. Skeleton is made of nitinol, which spans length of each component. Polytetrafluoroethylene (PTFE) graft material is attached to nitinol with polyethylene tape.

 

Figure 7
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Fig. 3A —Medtronic Talent (Medtronic Medical) stent-graft system. Photograph (courtesy of Medtronic Vascular, Santa Rosa, CA) (A), radiograph (B), and coronal maximal-intensity-projection image from contrast-enhanced MR angiography (C). Endograft is self-expanding modular stent-graft system composed of serpentine-shaped nitinol stents inlaid in woven polyester fabric.

 

Figure 8
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Fig. 3B —Medtronic Talent (Medtronic Medical) stent-graft system. Photograph (courtesy of Medtronic Vascular, Santa Rosa, CA) (A), radiograph (B), and coronal maximal-intensity-projection image from contrast-enhanced MR angiography (C). Endograft is self-expanding modular stent-graft system composed of serpentine-shaped nitinol stents inlaid in woven polyester fabric.

 

Figure 9
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Fig. 3C —Medtronic Talent (Medtronic Medical) stent-graft system. Photograph (courtesy of Medtronic Vascular, Santa Rosa, CA) (A), radiograph (B), and coronal maximal-intensity-projection image from contrast-enhanced MR angiography (C). Endograft is self-expanding modular stent-graft system composed of serpentine-shaped nitinol stents inlaid in woven polyester fabric.

 

Postoperative Complications
Top
Abstract
Introduction
Abdominal Aortic Endografts
Postoperative Complications
MR Protocol and Technique
Imaging Characteristics in the...
Summary
References
 
Endoleak
The most common complication, occurring in 10-25% of cases [7], is an endoleak or continued perfusion of the aneurysm sac, possibly leading to its progressive expansion. Several endoleak types have been described. A type 1 endoleak is an incomplete seal of the proximal or distal endograft attachment site (Fig. 4). A type 2 endoleak is related to retro-grade flow into the aneurysm from a patent side branch, most commonly the inferior mesenteric (Fig. 5) or lumbar arteries. A type 3 endoleak results from separation of the modular components or a tear in the endograft fabric. A type 4 endoleak is related to the porosity of the device fabric and is rarely seen in the postoperative setting.


Figure 10
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Fig. 4 —81-year-old man with proximal type 1 endoleak 6 months after endovascular aneurysm repair with Talent (Medtronic Medical) bifurcated device. Coronal maximal-intensity-projection image from contrast-enhanced MR angiography shows large collection of contrast material to left of device, originating (arrow) from proximal seal zone.

 

Figure 11
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Fig. 5 —76-year-old man with type 2 endoleak after endovascular aneurysm repair with Talent (Medtronic Medical) device. Selected frame from coronal contrast-enhanced MR angiography shows perfusion of aneurysm sac and patent inferior mesenteric artery (arrow).

 
Several studies have shown that MR angiography is more sensitive for endoleak detection than MDCTA [2, 6]. Similar research has shown MR angiography to be more specific for characterizing the extent of an endoleak and determining its type [2]. Time-resolved or dynamic contrast-enhanced MR angiography allows rapid visualization of vascular flow from which a virtual MR flush angiogram is created [4-6]. This allows visualization of flow direction in an endoleak and, therefore, determination of the endoleak type (Fig. 6A, 6B, 6C). In one study at a single institution from June 2002 to June 2003, 12 patients with documented endoleaks after endovascular repair of aortic aneurysms (10 abdominal and two thoracic) underwent time-resolved MR angiography to identify and characterize the endoleak [4]. All time-resolved MR angiography findings correlated with conventional angiography in characterization of the endoleak type.


Figure 12
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Fig. 6A —69-year-old man with type 2 endoleak after endovascular aneurysm repair with Gore Excluder (Gore Medical). Selected frames from coronal time-resolved MR angiography sequence show this endoleak originating from inferior mesenteric artery, which is perfused via arc of Riolan (arrow, B) to left of endograft.

 

Figure 13
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Fig. 6B —69-year-old man with type 2 endoleak after endovascular aneurysm repair with Gore Excluder (Gore Medical). Selected frames from coronal time-resolved MR angiography sequence show this endoleak originating from inferior mesenteric artery, which is perfused via arc of Riolan (arrow, B) to left of endograft.

 

Figure 14
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Fig. 6C —69-year-old man with type 2 endoleak after endovascular aneurysm repair with Gore Excluder (Gore Medical). Selected frames from coronal time-resolved MR angiography sequence show this endoleak originating from inferior mesenteric artery, which is perfused via arc of Riolan (arrow, B) to left of endograft.

 
Endotension
Previous authors have suggested that aneurysm sac expansion can occur even in the absence of an endoleak [7]. This rare phenomenon is known as endotension, and its mechanism remains controversial. In the strictest sense, endotension is defined as persistent elevated pressure within the excluded aneurysm sac in the absence of any demonstrable endoleak, with or without growth in sac diameter. It has been postulated that endotension may result from transudation of serous blood components and pressure through the stent-graft and thrombus, which seal the aneurysm sac from flowing blood. This fluid accumulation is conceptually analogous to a hygroma (Fig. 7A, 7B, 7C, 7D, 7E, 7F). Other proposed causes of endotension include missed endoleaks and endograft migration.


Figure 15
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Fig. 7A —82-year-old woman with enlarging aneurysm sac after thoracic endovascular aneurysm repair with Gore Excluder (Gore Medical). CT angiogram from July 1999 (A) shows aneurysm diameter of 7.0 cm; CT angiogram from July 2003 (B) shows aneurysm diameter of 10.0 cm.

 

Figure 16
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Fig. 7B —82-year-old woman with enlarging aneurysm sac after thoracic endovascular aneurysm repair with Gore Excluder (Gore Medical). CT angiogram from July 1999 (A) shows aneurysm diameter of 7.0 cm; CT angiogram from July 2003 (B) shows aneurysm diameter of 10.0 cm.

 

Figure 17
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Fig. 7C —82-year-old woman with enlarging aneurysm sac after thoracic endovascular aneurysm repair with Gore Excluder (Gore Medical). Axial, contrast-enhanced fat-saturated T1-weighted MR image from August 2003 (C) and axial steady-state free procession (SSFP) image from August 2003 (D). Four years after thoracic endovascular aneurysm repair, CT angiogram (B) shows no evidence of endoleak, but aneurysm sac has grown by 3.0 cm. Axial, contrast-enhanced fat-saturated T1-weighted MR image (C) also shows no endoleak, but axial SSFP image (D) shows diffuse high signal within aneurysm sac, suggesting endotension.

 

Figure 18
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Fig. 7D —82-year-old woman with enlarging aneurysm sac after thoracic endovascular aneurysm repair with Gore Excluder (Gore Medical). Axial, contrast-enhanced fat-saturated T1-weighted MR image from August 2003 (C) and axial steady-state free procession (SSFP) image from August 2003 (D). Four years after thoracic endovascular aneurysm repair, CT angiogram (B) shows no evidence of endoleak, but aneurysm sac has grown by 3.0 cm. Axial, contrast-enhanced fat-saturated T1-weighted MR image (C) also shows no endoleak, but axial SSFP image (D) shows diffuse high signal within aneurysm sac, suggesting endotension.

 

Figure 19
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Fig. 7E —82-year-old woman with enlarging aneurysm sac after thoracic endovascular aneurysm repair with Gore Excluder (Gore Medical). To confirm diagnosis of endotension, patient underwent direct aneurysm sac aspiration with CT guidance (arrow, E) to sample contents of sac. Approximately 150 mL of serosanguineous fluid was sampled and is shown in photograph (F). This confirmed diagnosis of sac hygroma, which is one possible cause of endotension.

 

Figure 20
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Fig. 7F —82-year-old woman with enlarging aneurysm sac after thoracic endovascular aneurysm repair with Gore Excluder (Gore Medical). To confirm diagnosis of endotension, patient underwent direct aneurysm sac aspiration with CT guidance (arrow, E) to sample contents of sac. Approximately 150 mL of serosanguineous fluid was sampled and is shown in photograph (F). This confirmed diagnosis of sac hygroma, which is one possible cause of endotension.

 
Embolization Follow-Up
The radiologist performing MR surveillance must be cognizant of previous embolization procedures because stainless steel coils create significant bloom artifact, which limits evaluation of the device and the aortic aneurysm (Fig. 8A, 8B). Platinum embolization coils are nearly transparent on MRI/MRA and are well suited for patients undergoing postoperative surveillance (Fig. 9A, 9B).


Figure 21
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Fig. 8A —82-year-old man after endovascular aneurysm repair with AneuRx endograft (Medtronic Medical). Follow-up imaging shows enlarging aneurysm sac. Any stainless steel products (coils, bare stents, and covered stents) produce significant metallic artifact on MRI, preventing evaluation of aneurysm sac with this technique, as shown in this axial, contrast-enhanced fat-saturated T1-weighted MR image (A). Patient underwent embolization of one internal iliac artery with four stainless steel coils. Patient eventually underwent MDCT angiography (B), which revealed complex type 1 endoleak. As result, many institutions have shifted to use of only platinum coils for embolization procedures.

 

Figure 22
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Fig. 8B —82-year-old man after endovascular aneurysm repair with AneuRx endograft (Medtronic Medical). Follow-up imaging shows enlarging aneurysm sac. Any stainless steel products (coils, bare stents, and covered stents) produce significant metallic artifact on MRI, preventing evaluation of aneurysm sac with this technique, as shown in this axial, contrast-enhanced fat-saturated T1-weighted MR image (A). Patient underwent embolization of one internal iliac artery with four stainless steel coils. Patient eventually underwent MDCT angiography (B), which revealed complex type 1 endoleak. As result, many institutions have shifted to use of only platinum coils for embolization procedures.

 

Figure 23
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Fig. 9A —72-year-old man after endovascular aneurysm repair with Talent (Medtronic Medical) device and embolization of type 2 endoleak with platinum coils. MDCT angiography follow-up shows significant metallic artifact, preventing detailed visualization and analysis of aneurysm sac to determine if there is persistent endoleak.

 

Figure 24
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Fig. 9B —72-year-old man after endovascular aneurysm repair with Talent (Medtronic Medical) device and embolization of type 2 endoleak with platinum coils. Axial, contrast-enhanced, fat-saturated T1-weighted MR image provides optimal visualization of the aneurysm sac because platinum coils produce little or no artifact on MRI. No endoleak is noted.

 
Limb Occlusion
Limb occlusions are less common than endoleaks, occurring in approximately 3% of aneurysms treated with endografts [8]. This complication occurs when the limbs of the endograft become twisted or kinked, obscuring blood flow to the ipsilateral lower extremity and possibly causing acute limb ischemia (Fig. 10A, 10B).


Figure 25
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Fig. 10A —77-year-old man with sudden onset of left leg pain 3 months after endovascular aneurysm repair with AneuRx endograft (Medtronic Medical). Coronal maximal-intensity-projection image from contrast-enhanced MR angiography (A) and axial contrast-enhanced fat-saturated T1-weighted MR image (B) show occluded left iliac limb (arrow, B). Patient underwent urgent femoral-femoral bypass to treat acute limb ischemia.

 

Figure 26
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Fig. 10B —77-year-old man with sudden onset of left leg pain 3 months after endovascular aneurysm repair with AneuRx endograft (Medtronic Medical). Coronal maximal-intensity-projection image from contrast-enhanced MR angiography (A) and axial contrast-enhanced fat-saturated T1-weighted MR image (B) show occluded left iliac limb (arrow, B). Patient underwent urgent femoral-femoral bypass to treat acute limb ischemia.

 

MR Protocol and Technique
Top
Abstract
Introduction
Abdominal Aortic Endografts
Postoperative Complications
MR Protocol and Technique
Imaging Characteristics in the...
Summary
References
 
The routine protocol used at our institution for postoperative endovascular aneurysm repair surveillance includes unenhanced and contrast-enhanced T1-weighted images and axial T2-weighted and steady-state free procession (SSFP) images. The contrast material is administered dynamically and divided into two injections. The first injection is used for time-resolved MR angiography to aid in endoleak detection, and the second injection is used with higher-spatial-resolution MR angiography for better depiction of anatomy.

SSFP imaging produces high signal-to-noise ratio images with T2 and T1 weighting [4-6]. Chronic thrombus shows low signal intensity, and noncoagulated blood exhibits high signal intensity on this sequence, making it an ideal tool for characterizing aneurysm sac contents and determining whether there is an endoleak or endotension (Fig. 11A, 11B, 11C).


Figure 27
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Fig. 11A —Three different patients (72-year-old woman [A], 68-year-old man [B], and 73-year-old man [C]) who underwent endovascular aneurysm repair. Steady-state free procession (SSFP) images of AneuRx (Medtronic Medical) (A), Talent (Medtronic Medical) (B), and Gore (Gore Medical) (C) endografts show aneurysm sac and characterize its contents without artifact from stent-graft. Sac contents appear as low signal when there is no endoleak and thrombus has begun to involute (A). When there is endoleak, there is heterogeneous signal within aneurysm sac, with focal areas of high signal (B). When aneurysm sac contents are uniformly bright in signal (C) and sac either is stable in diameter or has started to expand, endotension is thought to be present. In this scenario, there is typically no enhancement of sac contents after contrast administration.

 

Figure 28
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Fig. 11B —Three different patients (72-year-old woman [A], 68-year-old man [B], and 73-year-old man [C]) who underwent endovascular aneurysm repair. Steady-state free procession (SSFP) images of AneuRx (Medtronic Medical) (A), Talent (Medtronic Medical) (B), and Gore (Gore Medical) (C) endografts show aneurysm sac and characterize its contents without artifact from stent-graft. Sac contents appear as low signal when there is no endoleak and thrombus has begun to involute (A). When there is endoleak, there is heterogeneous signal within aneurysm sac, with focal areas of high signal (B). When aneurysm sac contents are uniformly bright in signal (C) and sac either is stable in diameter or has started to expand, endotension is thought to be present. In this scenario, there is typically no enhancement of sac contents after contrast administration.

 

Figure 29
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Fig. 11C —Three different patients (72-year-old woman [A], 68-year-old man [B], and 73-year-old man [C]) who underwent endovascular aneurysm repair. Steady-state free procession (SSFP) images of AneuRx (Medtronic Medical) (A), Talent (Medtronic Medical) (B), and Gore (Gore Medical) (C) endografts show aneurysm sac and characterize its contents without artifact from stent-graft. Sac contents appear as low signal when there is no endoleak and thrombus has begun to involute (A). When there is endoleak, there is heterogeneous signal within aneurysm sac, with focal areas of high signal (B). When aneurysm sac contents are uniformly bright in signal (C) and sac either is stable in diameter or has started to expand, endotension is thought to be present. In this scenario, there is typically no enhancement of sac contents after contrast administration.

 

Imaging Characteristics in the Postoperative Patient
Top
Abstract
Introduction
Abdominal Aortic Endografts
Postoperative Complications
MR Protocol and Technique
Imaging Characteristics in the...
Summary
References
 
If there is no endoleak or endotension post-operatively, the aneurysm sac contents will show hypointensity on both T1-weighted and T2-weighted images, no areas of enhancement after dynamic contrast administration, and diffuse low signal on SSFP imaging. Typical MRI findings associated with endoleaks include aneurysm sac contents with intermixed areas of variably increased or decreased intensity on T1-weighted and T2-weighted images and areas of enhancement after dynamic contrast administration. These heterogeneous areas appear as increased signal on SSFP imaging, and correlation with site and direction of flow enables characterization of the endoleak type. MRI characteristics of endotension include aneurysm sac contents that show low T1 signal and high T2 signal, no areas of enhancement after dynamic contrast administration, and uniform high signal on SSFP imaging (Figs. 7A, 7B, 7C, 7D, 7E, 7F and 11A, 11B, 11C). In the setting of limb occlusion, there is no flow identified in the stent-graft (Fig. 10A, 10B).


Summary
Top
Abstract
Introduction
Abdominal Aortic Endografts
Postoperative Complications
MR Protocol and Technique
Imaging Characteristics in the...
Summary
References
 
MR angiography and CT angiography are both used for the surveillance of patients after abdominal aortic aneurysm endovascular repair. Although both techniques are noninvasive, MR angiography offers improved sensitivity and specificity for detecting complications in patients after endograft placement compared with CT angiography. Time-resolved MR angiography characterizes the endoleak type, and SSFP pulse sequencing detects the presence of an endoleak or endotension with-out the use of IV contrast material.


References
Top
Abstract
Introduction
Abdominal Aortic Endografts
Postoperative Complications
MR Protocol and Technique
Imaging Characteristics in the...
Summary
References
 

  1. Parodi JC, Palmaz JC, Barone HD. Transfemoral intraluminal graft implantation for abdominal aortic aneurysms. Ann Vasc Surg 1991; 5:491 -499[CrossRef][Medline]
  2. Pitton MB, Schweitzer H, Herber S, et al. MRI versus helical CT for endoleak detection after endovascular aneurysm repair. AJR 2005; 185:1275 -1281[Abstract/Free Full Text]
  3. van der Laan MJ, Bartels LW, Bakker CJ, Viergever MA, Blankensteijn JD. Suitability of 7 aortic stentgraft models for MRI-based surveillance. J Endovasc Ther 2004;11 : 336-371[Medline]
  4. Lookstein RA, Goldman J, Pukin L, Marin ML. Time-resolved magnetic resonance angiography as a noninvasive method to characterize endoleaks: initial results compared with conventional angiography. J Vasc Surg 2004; 39:27 -33[CrossRef][Medline]
  5. Lookstein RA, Honig S, Cohen EI, et al. MRI of aortic stent grafts using SSFP to diagnose endoleaks and endotension: single center experience. AJR 2006;186 [American Roentgen Ray Society 106th Annual Meeting Abstract Book suppl]: A37-A38
  6. van der Laan MJ, Bakker CJ, Blankensteijn JD, Bartels LW. Dynamic CE-MRA for endoleak classification after endovascular aneurysm repair. Eur J Vasc Endovasc Surg 2006;31 : 130-135[CrossRef][Medline]
  7. White GH, May J, Petrasek P, Waugh R, Stephen M, Harris J. Endotension: an explanation for continued AAA growth after successful endoluminal repair. J Endovasc Surg 1999;6 : 308-315[CrossRef][Medline]
  8. Ohki T, Veith F, Shaw P, et al. Increasing incidence of midterm and long-term complications after endovascular graft repair of abdominal aortic aneurysms: a note of caution based on a 9-year experience. Ann Surg 2001; 234:323 -334[CrossRef][Medline]

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