Time Of Flight Magnetic Resonance Angiography Biology Essay


Magnetic Resonance Angiography (MRA) refers to a group of techniques based on Magnetic Resonance Imaging (MRI) to image blood vessels. MRA may be performed with various techniques, each with its advantages, disadvantages, and pitfalls. Early attempts at vessel analysis made use of time-of-flight and phase-contrast techniques, while more recently contrast-enhanced MRA has gained wide acceptance, in many cases relegating conventional angiography to a secondary role during image guided vascular intervention (Westbrooke et al 2005).

Time of flight MRA (TOF) is a noninvasive technique to image arterial or venous blood vessels without the need of a contrast agent. It is used for the imaging of vessels, most commonly in the head and neck. It produces vascular contrast by manipulating the longitudinal magnetization of the stationary spins, and is dependent on the flow and the movement of protons in blood through the imaging plane. TOF MRA uses a coherent gradient echo pulse sequence in combination with gradient moment rephrasing to enhance flow (Muhs et al 2007).

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In TOF-MRA, a single measurement is performed, with the stationary tissue signal suppressed relative to the flowing tissue signal. The signal in the slice that is to be imaged is saturated with rapid RF pulses. Background or stationary tissues will be suppressed by the RF pulse, whereas fresh-moving blood entering the slice after the RF pulse will retain its signal intensity. A volume of blood will be at a different location at the time of each excitation pulse due to its motion during TR. The signal from the blood volume is largest at the entry point of the slice because it has not undergone any excitation pulse. As the blood volume travels through the slice, it becomes increasingly saturated (Vlaardingerbroek et al 2003). The degree of blood saturation, and the contrast between blood and background tissue thus depends on the slice thickness, TR, excitation angle, and flow velocity.

TOF MRA may be acquired in either 2D (slice by slice) or 3D (volume) acquisition modes, and is still used as an essential component of neurovascular imaging because it is very sensitive to flow and can be performed with very high resolution. In 2D TOF MRA, a flip angle of 45-60 degrees combined with a TR of 40-50ms us usually sufficient to maximize signal without suppressing signal from the flowing blood volume. To evaluate arterial flow signals, saturation pulses may be applied in the direction of venous flow. 3D volume imaging offers high signal to noise ratio (SNR) and thin contiguous slices for good resolution. 3D TOF-MRA is time-consuming, taking approximately 5 to 10 minutes, depending on coverage and desired spatial resolution. For this reason, its applications are limited to structures such as the head and neck, which can be immobilized during the acquisition (Brown & Semelka 2010). Because of the widespread acceptance of neurovascular MR imaging (MRI), 3D TOF-MRA of the intracranial arteries is the single most widely used MRA technique of any kind. It is also commonly used for imaging the cervical carotid arteries. 2D TOF is optimal in areas of slower velocity flow, and when a large area of coverage is required (Mitra 2006).

TOF techniques suffer from various limitations. One is that they provide only a qualitative assessment of flow velocity. TOF-MRA is hampered by flow voids or low signal intensity regions intravascularly. Flow voids can be caused by in-plane saturation, which occurs when a blood vessel travels in the same plane as the imaging slice, thereby saturating the aortic blood, and also by post-stenotic turbulence distal to a stenosis, which accelerates the phase dispersion (Westbrooke et al 2005).

Another limitation is that there is incomplete suppression of the background tissue, due to the faster T1 relaxation times of the stationary tissues relative to the blood, particularly fat. This can be minimized by choosing a relatively short TE so that the signals from water and fat remain out of phase with each other, thereby cancelling each other out. Another option is to use magnetization transfer contrast (MTC). With MTC, off resonance RF pulses are applied to the imaging sequences to suppress the signals from macromolecules, such as those found in gray and white matter in brain tissue, thus enhancing the ability for small vessel detection at the expense of increased TR and relative fat signal (Brown & Semelka 2010). Figure 1 demonstrates the effects of using MT pulse. There is a clear reduction of background gray and white matter in image 1c compared to 1a, and improved visualization of vessels in 1d compared to 1b.

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The main advantages of TOF MRA is the reasonably imaging times, its sensitivity to slow flow, and reduced sensitivity to intra-voxel dephasing. However, TOF MRA tends to be sensitive to T1 effects and has saturation of in-plane flow. Enhancement is also limited to either flow entering the field of view (FOV), or very high velocity flow (Westbrooke et al 2005).

Figure 1. TOF MRA showing effects of MTC pulse. (a) Source image from data set acquired without MT pulse. (b) Transverse processed image of (a). (c) Source image from data set acquired with MT pulse. (d) Transverse processed image of (c) (Brown & Semelka 2010).

Phase Contrast MRA

Phase contrast magnetic resonance angiography (PC-MRA) also involves exploiting the motion of blood, although it is not limited by the in-plane flow voids that plague TOF-MRA. PC-MRA uses the velocity differences, and hence the phase shifts in moving spins, to provide image contrast in flowing vessels. It is sensitive to flow within, and that coming perpendicularly into the FOV and the slice (Hashemi et al 2003).

PC-MRA involves using a bipolar flow-encoding gradient, which is basically a magnetic field gradient that reverses directions at the midpoint. This bipolar gradient will induce a velocity-dependent phase shift in moving systems but no phase shift in stationary ones. During PC-MRA, two images are obtained immediately after each other, typically using opposite bipolar gradients, which will induce opposite phase shifts in the moving blood data (see Figure 2). The images are subtracted from each other, which amplifies the signal from vascular tissue flow in which the subtraction of opposite phase shifts results in an addition. The unsubtracted combinations of flow sensitized image data are known as magnitude images, while the subtracted combinations are called phase images (Muhs et al 2007). Static tissues such as muscle or bone will subtract out.

Figure 2. Magnitude (left) and phase (right) images of a PC-MRA of the aortic arch. The flow-encoding gradients encode for flow in the superior-inferior direction, with flow in the superior direction being bright and that in the inferior direction appearing dark. The variation in color is an indicator of the change in velocity (Muhs et al 2007).

PC-MRA can also be sensitized to flow velocity. Velocity encoding technique (VENC) is the maximum encoding velocity, and it compensates for projected flow velocity within vessels by controlling the amplitude or strength of the bipolar gradient (Hashemi et al 2003). The magnitude and duration of the flow-encoding gradient determine the VENC that can be encoded for over a phase range of negative 180 degrees to positive 180 degrees. If the VENC is not chosen correctly, flow velocities greater than this value can generate an aliasing artifact owing to the phase aliasing over the negative 180 degrees to positive 180 degrees range. When the VENC is chosen correctly, the phase shift is proportional to the velocity of the blood and can be used to determine the velocity of the blood (Goyen & Heuser 2000). With high VENC settings, intraluminal signal is improved, but vessel wall delineation is compromised.

PC-MRA can be acquired with the use of either 2D or 3D acquisition strategies. 2D techniques provide acceptable imaging times and flow direction information. However, 2D acquisitions cannot be reformatted and viewed in other imaging planes. 3D PC-MRA offers superior SNR and spatial resolution to 2D imaging techniques, and the ability to reformat in a number of imaging planes retrospectively. However, the trade-off is that imaging time would increase with the TR, NEX, the number of phase encoding steps, the number of slices, and the number of flow encoding axes selected (Goyen & Heuser 2000). For this reason, scan times are at times long.

Many post-processing techniques use the complex data from the PC-MRA images to determine velocity and volume flow rate in the blood vessels. This technique is particularly useful when flow and velocity information is needed, as in cardiac and thoracic aorta imaging. Despite the slowness of this method, the strength of the technique is that in addition to imaging flowing blood, quantitative measurements of blood flow can occur at the same time, there is reduced intra-voxel dephasing, and increased background suppression. However, PC-MRA can be more sensitive to turbulence, and has longer imaging times with 3D techniques (Vlaardingerbroek et al 2003).

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Contrast Enhanced MRA

Contrast-enhanced MRA (ceMRA) is a more invasive technique that involves the introduction of a bolus injection of contrast medium followed by a 3D T1 gradient echo sequence during a dynamic imaging sequence. Gadolinium chelate agents are typically used for ceMRA because they are paramagnetic. This means that they cause shortening of the T1 relaxation of blood compared with background tissue leading to the high signal intensity of blood on T1 weighted sequences. Unlike TOF MRA or PC MRA imaging, the signal of the blood in ceMRA is based on the intrinsic T1 signal of blood rather than on flow effects, hence making this technique less flow sensitive. This sequence is commonly timed to the arterial phase and then repeated several times to acquire images during intermediate and venous phases of the vascular system (U-King-Im et al 2004).

CeMRA is based on the presence of gadolinium in the blood, independent of the flow waveform and flow velocity in the vessels. It does not rely upon the physiologic flow of in-phase spins for signal generation and is free from many of the limitations of TOF MRA and PC-MRA that were considered above. The basic pulse sequence for ceMRA is an ultra-short TR/TE 3D spoiled gradient echo sequence and has a relatively simple structure. The TR is made as short as possible to speed up image acquisition and capture the first pass of contrast (Yang et al 2005). The presence of contrast makes the blood immune to saturation, so the short TR tends to saturate only background tissue. The TE is also made as short as possible, so as to limit any flow-induced dephasing effects. For this reason, vessel diameters measured on high-quality ceMRA studies tend to have far less exaggeration of stenosis due to turbulent flow (Zhang et al 2007).

Several important issues must be taken into consideration for image optimization, including the timing, amount, and rate of the injection of contrast agent. The goal is to record the central region of k-space during the maximum enhancement of the artery. The center of k-space should be acquired during the time of highest contrast agent concentration. Also, a high rate of change of the contrast agent concentration during the acquisition of central k-space must be avoided to prevent ringing artifacts, arising in the Fourier transform. When agent administration and imaging are timed properly, ringing artifacts can be reduced or even eliminated (Zhang et al 2007). CeMRA has proven to be highly accurate, especially when compared with non-contrast techniques. It is a robust, reproducible technique that can be performed in seconds rather than minutes with few flow-related artifacts. Overestimation of stenosis that can occur in other techniques such as TOF MRA is also avoided with ceMRA (see Figure 3).

Figure 3 a) Conventional digital subtraction angiogram of the iliac and common femoral arteries. B) 2D TOF MIP image. C) 3D ceMRA MIP. The ceMRA image demonstrates the overestimation of stenoses in the right common iliac and left common femoral arteries on the TOF images. The arrows indicate stenoses and how the same stenosis is imaged differently with different techniques (Yang et al 2005).


3D TOF-MRA has long been the technique of choice for non-invasive imaging of the head and neck arteries. Indeed, when using an optimized technique on a cooperative patient, TOFMRA allows superb visualization of the circle of Willis, which provides information about vascular patency, caliber, and the presence and location of intracranial aneurysms. However, knowledge of the limitations of TOF MRA is important so that artifactual stenoses and occlusions are recognized. The importance of a complete data review, particularly of the source data images, cannot be stressed enough, so that these artifacts are not misinterpreted. Recently, hardware technology has evolved to the point at which image quality with ceMRA may rival or exceed that of TOF MRA in the supra-aortic circulation (Mitra et al 2006). It could be argued that, with advanced machine hardware, ceMRA may supersede TOF MRA for most applications in the head and neck.

The potential application of PC MRA to a variety of vascular territories has been evaluated, with generally satisfactory results. The strength of this method lies in its ability to depict directional flow, as well as allowing quantitative analysis of flow characteristics. However, with the recent development of rapid high-resolution volumetric ceMRA techniques, PC-MRA is often reserved for research applications (Goyen & Heuser 2000).

The spatial resolution of modern ceMRA continues to increase to such a degree that confident visualization of peripheral vessels measuring only 2 to 3 mm is now possible. As a result, ceMRA has replaced conventional catheter angiography in many applications, allowing an alternative, less invasive, and clinically viable approach to vascular imaging (U-King-Im et al 2004). For this reason, ceMRA has been successfully applied to every anatomic region, such that, in the absence of specific contraindications, its use should always be considered.


The advent of parallel imaging has helped to consolidate the role of ceMRA as a practical diagnostic tool. Nonetheless, the versatility of non-enhanced techniques, such as TOF MRA and PC MRA, renders them viable alternatives to ceMRA in patients in whom a contrast agent is contraindicated, refused, or undesirable. As MR technology continues to evolve, newer and more powerful implementations of both contrast-enhanced and nonââ‚¬"contrast-enhanced MRA will undoubtedly emerge.