Combining a perfectly timed gadolinium contrast agent injection with three-dimensional (3D) spoiled gradient-echo (SPGR) magnetic resonance (MR) imaging produces high signal-to-noise ratio (S/N) MR angiograms covering extensive regions of vascular anatomy within a breath hold (1, 2, 3, 4, 5, 6, 7, 8, 9, 10). This article provides information for radiologists on
1. Principles of 3D gadolinium-enhanced MR angiography.
2. Patient set-up and positioning.
3. Selection of optimal imaging parameters.
4. Timing of the gadolinium bolus.
5. Reconstruction of images on a computer workstation.
6. Identification of normal variants, postoperative cases, and common pathologic entities.
Principles of 3D Gadolinium-enhanced MR Angiography
Gadolinium is one of the rare earth elements in the transition group IIIb of the periodic table. Actually, it is not rare at all, but a rather common element found throughout the earth's crust. It has eight unpaired electrons in its outer shell, which causes its paramagnetic effects. Gadolinium by itself can cause heavy metal poisoning. However, when bound to a chelator, it is safe for intravenous injection, yet remains paramagnetic. It shortens the T1 of blood in the region of the gadolinium molecule according to the following equation (1):
1/T1=1/1,200 + (R1 × [Gd]),
where R1 is the T1 relaxivity of the gadolinium chelate, [Gd] is the gadolinium concentration in the blood, and 1,200 is the blood T1 (in msec) without gadolinium.
Figure 1. Effect of gadolinium concentration on blood T1. (The graph was calculated with Microsoft Excel 97 [Microsoft, Redmond, Wash] by using the above formula.)
The blood [Gd] must be greater than 1.0 mmol/L for T1 to be less than 270 msec, which is the T1 of fat at 1.5 T (1, 5). This is the property which is important for increasing the MR signal intensity of blood on contrast-enhanced SPGR images. Note that this T1 shortening effect is maximized by using gadolinium chelates with the highest relaxivity and by having a high gadolinium concentration in the blood.
Gadolinium Safety
Gadolinium contrast agents have an extraordinarily favorable safety profile. There is no clinically detectable nephrotoxicity for gadopentetate dimeglumine (Magnevist; Berlex Imaging, Wayne, NJ), gadoteridol (ProHance; Bracco Diagnostics, Princeton, NJ), or gadodiamide (Omniscan; Nycomed Amersham, Princeton, NJ) even at high doses (11). In addition, they have a very low frequency of adverse events. Idiosyncratic reactions are rare, and serious adverse events are extremely rare (1 in 20,000) (12). Note that important contraindications to gadolinium include pregnancy and a history of a life-threatening reaction to gadolinium itself. In patients with poor renal function, there may be delayed excretion of gadolinium contrast agents.
Gadolinium Dose
With intravenous injection, gadolinium is initially in the arm vein, then the pulmonary circulation, then the arteries; eventually it is distributed throughout the circulatory system. Within a few minutes, there is redistribution into the extracellular fluid space. To make blood bright compared with all background tissues, it is necessary to give a sufficient dose of gadolinium. Two or three bottles (20 mL each) of the gadolinium contrast agent (about 0.3 mmol/kg gadolinium) is usually sufficient for an average or heavy person when imaging in the equilibrium phase. However, arteries are best imaged during the arterial phase of gadolinium infusion. This gives a higher arterial S/N and eliminates the confusion caused by overlapping venous enhancement. It may seem that a fast acquisition is necessary to capture the contrast agent bolus during the brief moment when the agent is present in the arteries but not yet in the veins. However, it is possible to take advantage of three important effects that allow the relatively slow MR acquisition to capture an arterial-phase image without having to use large amounts of gadolinium.
K Space
The most important effect is related to how MR data are mapped in k space. K space, or Fourier space, does not map to the image pixel by pixel. Rather, the information within k space determines spatial frequency features of the image. The low spatial frequency information, in the center of k space, dominates image contrast, while the higher spatial frequency data, at the periphery of k space, determines image detail. To obtain an arterial-phase image in which arteries are bright and veins are dark, it is essential that the central k-space data (ie, the low spatial frequency data) are acquired while the gadolinium concentration in the arteries is high but relatively lower in the veins. The presence of contrast agent is not as important for acquisition of peripheral k-space data. This trick allows a relatively long MR acquisition to achieve the image contrast associated with a brief window of time. That brief window of time is the instant when central k-space data are acquired. Therefore, it is critical to time the bolus for maximum arterial [Gd] during acquisition of central k-space data. With perfect bolus timing, high S/N arterial-phase images are possible with smaller doses of gadolinium.
Gadolinium Extraction
A second important effect is the extraction of gadolinium in the systemic capillary beds. This extraction results in venous blood tending to have a lower concentration of gadolinium relative to arterial blood, even for relatively long, sustained infusions lasting several minutes. This effect is not present in the cerebrovascular circulation because of the blood-brain barrier. Consequently, arterial-phase imaging in the central nervous system is more difficult.
Infusion Rate and Cardiac Output
A third effect is the relationship between arterial gadolinium concentration, the infusion rate, and cardiac output as follows:
[Gd]Arterial=Injection Rate/Cardiac Output
Figure 2. T1 versus injection rate at differing cardiac outputs.
This graph is a computer model generated for different cardiac outputs. Note that this graph is for static, nonmoving blood. The actual T1 of moving blood is even less than in the above graph. Notice that an injection rate of 0.2-0.3 mL/sec is required to decrease the blood T1 value to less than 150 msec in a patient with a cardiac output of 5 L/min. This is sufficiently below the T1 of fat (270 msec at 1.5 T) so that only the gadolinium in blood produces high signal intensity on T1-weighted SPGR images.
Arterial [Gd] is maximized by relaxing the patient to reduce cardiac output and by using a high infusion rate. However, fast infusion rates lasting for at least half of the acquisition time require large doses of gadolinium. The dose can be kept to a reasonable level by scanning rapidly. Fast acquisitions (<45 seconds) are possible with high performance gradient systems that allow short repetition and echo times, without having to make the bandwidth too wide. Fast acquisition has the additional benefit of making it possible for the cooperative patient to suspend breathing and to hold perfectly still.
Saline Flush and Intravenous Tubing
It is important to use intravenous (IV) line tubing that allows simultaneous attachment of separate syringes for the contrast agent and saline flush. The SmartSet (TopSpins, Ann Arbor, Mich), developed at the University of Michigan, has one-way valves that allow automatic switching between the contrast agent injection and saline flush so that there will be one continuous bolus with no gaps. By using the same tubing set for all patients receiving dynamic contrast agent injection, the operator becomes familiar with performing the injections and especially with the resistance to injection. It is then easier to concentrate on correctly timing the bolus and instructing the patient to suspend breathing.
Click here to view IV setup and use of SmartSet.
At least 20 mL of saline is recommended to adequately flush the contrast agent through the IV tubing and arm vein. By starting with a 30-mL saline-filled syringe, it is possible to initially prime the SmartSet with 8 mL of saline, test the IV once or twice with a 1-mL saline injection, and still have 20 mL left for the dynamic flush.
Gadolinium Dose
When beginning, we recommend use of two bottles (42 mL) for the average-size patient and three bottles (63 mL) for patients weighing more than 100 kg. Once you learn how to time the contrast agent injections perfectly, you will find it is possible to reduce the dose and still obtain diagnostic images.
Contrast Agent Bolus Timing
Perfect contrast agent bolus timing is crucial to ensure that the maximum arterial [Gd] occurs during the middle of the acquisition, when central k-space data are acquired. It is also essential that [Gd] not change too rapidly, as this will create a "ringing" artifact (13) (click here for example). Minimizing the ringing artifact requires that the contrast agent infusion last for at least half the duration of the 3D image acquisition. Bolus timing is difficult because the time required for the contrast agent bolus to travel from the injection site (typically an antecubital vein) to the artery being imaged is highly variable. For renal arteries, it may be only 10 seconds in a young, healthy person with a central intravenous line, or it may be as long as 50 seconds in an older patient with congestive heart failure and an intravenous line in the hand or wrist.
Timing for Long Acquisitions
For long acquisitions, lasting more than 100 seconds, timing is easy because errors of 10-15 seconds are small relative to the total scan duration. Use sequential ordering of k space, so that the center of k space is collected during the middle of the acquisition. Sequential ordering tends to result in fewer artifacts. Begin injecting the gadolinium just after initiating imaging. Finish the injection just after the midpoint of the acquisition, being careful to maintain the maximum injection rate for the approximately 10-30 seconds prior to the middle of the acquisition. This will ensure a maximum arterial [Gd] during the middle of the acquisition, when central k-space data are collected. To ensure full use of the entire dose of contrast agent, it is useful to flush the IV tubing with 20 mL of normal saline. This can be facilitated by using the SmartSet, which has ports for simultaneous attachment of contrast agent and saline syringes and valves for automatic switching between syringes. In this way, there is no delay between finishing the contrast agent injection and beginning the saline flush.
Timing for Fast (Breath-hold) Scans
For fast scans, less than 45 seconds in duration, contrast agent bolus timing is more critical and challenging. This is because bolus timing errors of 15 seconds can ruin a fast breath-hold scan. There are several approaches to determining the optimal bolus timing for these fast scans. The simplest, although least successful approach, is to guess on the basis of patient age, cardiac status, presence of aortic aneurysmal disease, and IV location. For a typical breath-hold scan duration of 35-45 seconds in a reasonably healthy patient with an IV site in the antecubital vein, a delay of approximately 10-12 seconds is appropriate. Therefore, in this scenario, begin the injection, and then 10 seconds later start imaging while the patient suspends breathing. If there is no convenient clock available to time this delay, take advantage of the natural rhythm of the patient's respiration. One deep breath in followed by a deep breath out takes approximately 4 seconds. Two breaths are eight seconds, followed by a deep breath in, 10 seconds, which represents the optimum delay between start of injection and beginning of scanning. If a patient is older and has a history of cardiac or aortic aneurysmal disease, add one or two extra breaths to the delay. Also, if the IV site is in the wrist, add an extra breath to the delay. Alternatively, if the patient is a marathon runner or you are injecting via a central line, it may be suitable to use only 1½ breaths of delay, or 6 seconds. A firm injection is necessary to keep the contrast agent bolus together. However, if the injection is too vigorous, it may cause rupture of the vein, with resulting extravasation of the contrast agent.
More reliable and precise techniques for determining the contrast travel time are also available. These include using a test bolus (14) to precisely measure the contrast travel time, using an automatic pulse sequence that monitors signal in the aorta and then initiates imaging after contrast is detected arriving in the aorta (Fluoroscopic triggering or MR SmartPrep) (15, 16), or imaging so rapidly that bolus timing is unimportant (10). A typical monitor signal graph is shown below.
Figure 3. Tracking signal versus time.
Blue line - MR signal intensity in volume of interest.
Green line - Level at which signal is 100% above baseline.
Red arrows - Time of injection and optimal time for imaging.
Note that the centric ordering of k space for the triggered acquisitions may create artifacts if the contrast agent bolus is still arriving when the scan is started. Sometimes this artifact may be reduced with sequential ordering. This artifact may also be reduced by delaying 5-8 seconds after detecting the leading edge of the bolus to give the contrast agent time to flow in completely and reach the plateau phase of the bolus.
Postprocessing of MR Data
Substantial improvement in image quality, and especially image contrast, can be attained through postprocessing techniques.
* Zero Padding
Image resolution can be increased with interpolation. One particularly useful interpolation scheme is known as zero padding. This involves filling out peripheral lines of k-space data with zeroes prior to performing the Fourier transform. Although no additional time is required for data collection, the Fourier transform will reconstruct more images with a smaller spacing. For example, with two-fold zero padding, if the partition thickness is 3 mm, the Fourier transform will reconstruct additional images that also have a 3-mm slice thickness but at 1.5-mm spacing with 50% overlap. This helps eliminate volume averaging and creates smooth visualization of small vessels on the reformatted maximum intensity projection (MIP) images. If available, two-fold zero padding in the slice direction is recommended.
* MR Digital Subtraction Angiography (DSA)
Image contrast can be improved by digital subtraction of precontrast image data from dynamic, arterial, or venous phase image data. This subtraction can be performed either slice-by-slice or prior to the Fourier transform by using a complex subtraction method. The improvement in contrast achieved with DSA may reduce the gadolinium dose required. However, there must be no change in the patient position between the precontrast and dynamic contrast-enhanced imaging. This requirement for no motion is easily met in the pelvis and legs, which can be sandbagged and strapped down. It is more difficult to achieve in the chest and abdomen, where respiratory, cardiac, and peristaltic motions are more difficult to avoid. Note that complex subtraction is generally performed automatically by the scanner before creating any of the images.
Multiplanar Reconstructions
Reformations and MIPs are essential for optimal assessment of vascular anatomy. Single-voxel-thick reformations and narrow subvolume MIPs show bifurcations and branch vessels in profile. This is important because atherosclerotic disease tends to be most severe at branch points. By creating subvolume MIPs of the 3D image data, these techniques help unfold tortuous vessels and eliminate the confusing overlap of vascular anatomy.
Creating an MIP Image
One approach to performing a subvolume MIP is to first load the entire 3D volume of arterial phase image data into the computer workstation 3D analysis program. Display a coronal MIP of the entire volume, an axial reformation, and an oblique view. On the coronal view, move the dot (which tracks the location) cranially and caudally while watching the axial reconstruction window to find the renal arteries. Display this subvolume of sagittal data as an MIP. Make this oblique MIP thick enough to encompass most of the aorta. Be certain to align the axis of the subvolume MIP so that it is parallel to the origin of the vessel. Although the entire length of the vessel may not be seen on this image, it will be an accurate representation of the vessel's origin, with no overlap from the aorta. This may then be repeated by moving the tracker dot on the axial image and watching the oblique view to create a sagittal view of the celiac and superior mesenteric arteries. This will show the celiac and superior and inferior mesenteric arteries, as well as the anterior and posterior margins of the aorta to best advantage.
Renal Artery Stenosis
Renal artery stenosis is an important cause of hypertension and renal failure (17, 18, 19, 20). This should be imaged with a comprehensive approach (11) that includes both morphologic and functional assessment of the renal vasculature.Many sequences are available which provide important information (21, 10, 22, 23, 24). We have chosen to do 3D phase contrast because of its simplicity and reliability (2).
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