Magnetic Resonance Angiography in Acute Stroke

David Yu, Pamela W. Schaefer, Guy Rordorf, and R. Gilberto Gonzalez

M AGNETIC RESONANCE angiography (MRA) is a range of magnetic resonance

techniques used in neuroradiology to evaluate major arteries, primarily for stenosis and aneu- rysm. Commonly, neck and intracranial arteries are assessed from the common carotid and vertebral artery origins to second order branches of the circle of Willis. Noncontrast enhanced MRA with time of flight (TOF) or phase contrast (PC) techniques is a physiologic evaluation with signal based on flow dynamics compared with contrast enhanced (ceMRA), which is more of an anatomic evalua- tion.

In the evaluation of cerebral ischemia, MRA is used to evaluate severity of stenosis or occlusion as well as collateral flow. At Massachusetts General Hospital, Boston, MA, the MRA protocol consists of a 2-dimensional (2D) TOF and ceMRA through the neck followed by a 3-dimensional (3D) TOF and 2D PC through the circle of Willis. For dissection, a fat saturated pregadolinium axial TI sequence through the neck is added (Fig 1).

NON-ceMRA

Non-ceMRA can be divided into TOF and PC techniques. Both TOF and PC MRA can be ac- quired in slices (2D) or slabs (3D).

TOF

In TOF MRA, vessel and background in an imaging volume are evaluated with a gradient echo sequence. Gradient echo imaging involves apply- ing a radiofrequency (RF) pulse followed by dephasing and rephasing gradients. After a series of RF pulses, the proton spins in the background become saturated and reach a steady state of low contribution to signal. In comparison, with inflow of blood in vessels, saturated proton spins are continuously being replaced by fresh unsaturated spins, and the background steady state is never

From the Neuroradiology Division and Stroke Service, Mas- sachusetts General Hospital and Harvard Medical School, Boston, MA.

Address reprint requests to R. Gilberto Gonzdlez, MD, PhD, Neuroradiology, GRB 285, Fruit Street, Massachusetts General Hospital, Boston, MA 02114-2696.

Copytight 2002, Elsevier Science (USA). All rights, reserved. 0037-198X/02/3703-0007535.00/0 doi: l O.1053/sroe.2002.34567

achieved. With more unsaturated spins, vessels are markedly hyperintense relative to background. The vessel contrast or flow-related enhancement is proportional to the velocity. A presaturation pulse is applied above the imaging volume to saturate the inflowing proton spins from veins so that visual- ization of arteries is not obscured. 1-3

Any process interfering with the inflow of blood into the imaging volume and the replacement of saturated proton spins by unsaturated spins results in loss of vascular signal. In 2D TOF, maximum flow-related enhancement occurs when an artery is perpendicular to the plane of imaging because the arterial segment in the imaging volume is mini- mized. This allows unsaturated spins, with inflow of arterial blood, to more rapidly replace saturated spins. Conversely, vessels traveling in the imaging plane suffer in-plane flow loss of enhancement because the spins are generally more saturated. In-plane loss of flow-related enhancement is often shown within the cavernous and petrous segments of the internal carotid artery (ICA) as well as the C1-C2 turns of the vertebral arteries. Flow turbu- lence similarly decreases the efficiency whereby saturated spins are replaced by unsaturated spins. Turbulence also causes intravoxel phase dispersion whereby spins within a voxel accumulate differing precessional phases varying more than from nor- mal laminar flow during the dephasing gradient. As a result, even with velocity compensation schemes, the rephasing gradient is unable to generate a strong echo. Turbulence-related loss of flow en- hancement is often shown at the carotid and other vessel bifurcations. Differentiation of turbulence- related loss of signal at bifurcations from actual stenosis often requires correlation with ceMRA (Fig 2). Saturation and intravoxel phase dispersion also explain why turbulent flow at and distal to a stenosis results in loss of signal and overestimation of both severity and length of stenosisY

Although normal brain tissue is well saturated and therefore low in signal intensity, substances with intrinsically short T1, such as methemoglobin in a blood clot, will not be completely saturated. This results in hyperintense regions on the TOF MRA. Because of this imaging effect, regions of intrinsically short T1 may be mistaken for regions of flow. If high-signal regions occur in an anatomic structure that does not involve flow, they may

212 Seminars in Roentgenology, Vol 37, No 3 (July), 2002: pp 212-218

MRA IN ACUTE STROKE 213

Fig 1. Dissection. (A) 2D TOF noncontrast MRA MIP shows short segmental tapered complete loss of flow-related en- hancement in the proximal right cervical ICA (arrow). (B) Fat saturated, nonenhanced axial T1 shows crescentic hyperin- tensity consistent with blood products within the intima of the right proximal ICA (arrow).

obscure signals from flowing vessels on the max- imum intensity projection (MIP) images. The short T1 of orbital and subcutaneous fat also results in significant signals on 3D TOF MRA. Segmenting out the intracranial vessels from these structures before obtaining MIP images or setting the echo time (TE) to 2.3 or 6.9 ms, making fat and water out of phase and therefore decreasing the signal intensity of fatty structures, decreases the obscura- tion of vessels.

In 2D TOF MRA, multiple thin, sequential, 1-mm thick slices are obtained. A large flip angle RF pulse is used to saturate background protons in the imaging slice. However, protons in arterial segments lying within the imaging plane also become rapidly saturated with signal loss. Com- pared with 3D TOF, this technique has fewer saturation effects as spins travel through the mul- tiple thin slices and allows for coverage of a larger

area than 3D TOF techniques. However, it is more susceptible to in-plane saturation effects and loss of signal from intravoxel dephasing.

In 3D TOF MRA, a volume of tissue covering the skull base to the circle of Willis is obtained and divided into 1-mm thick slices with an extra-phase encoding step. A small flip angle RF pulse de- creases the rate of arterial saturation in the imaging slab but also decreases the background saturation as well, whereas a larger flip angle results in arterial saturation especially in the end of the volume. Typically, a ramped flip angle is used to maximize vessel to background contrast while minimizing saturation effects. A magnetization transfer pulse is used to maximize vessel to back- ground contrast. Compared with 2D TOF, this technique has better spatial resolution and vessel contrast but is more susceptible to saturation ef- fects and can only cover a relatively small volume.

214 YU ET AL

Fig 2. ICA origin apparent stenosis. (A) 2D TOF noncom trast NIRA shows focal severe loss of flow related enhance- ment at left ICA origin (arrow). (B) celVIRA shows that loss of signal on noncontrast MRA related to turbulence rather than actual stenosis.

Multiple overlapping thin slab acquisition is a hybrid TOF MRA technique that involves acquir- ing partially overlapping thin imaging slabs and discarding the overlapping end slices of each slab to create one 3D slab. Contrast in the end slices of each slab is usually suboptimal due to saturation. Therefore, multiple overlapping thin slab acquisi- tion extracts the central portion of each overlap- ping thin slab with the optimal vascular signal and background saturation and pieces them together to form a large imaging volume with strong relative vascular signal. This technique has better spatial resolution and image contrast compared with 2D TOF MRA but fewer saturation effects compared with 3D TOF MRA.

PC M R A

PC MRA uses a gradient echo sequence to preferentially enhance vessel over background. In gradient echo imaging, after a RF pulse, dephasing and then rephasing (or bipolar) gradients are ap- plied. Proton precession frequency is proportional to the external magnetic field according to the Larmor equation. Therefore, the phase that is acquired by the spinning proton is greatly influ- enced by the strength of the gradient. The rephas- ing gradient is equal but opposite to the dephasing gradient so that stationary spinning protons will reverse their spins to the same magnitude to refocus and result in a gradient recalled echo. Proton spins in a vessel traveling along the direc- tion of the bipolar gradients move through dephas- ing and then rephasing gradients. Protons moving in the direction of increasing gradients will expe- rience a continuously increasing magnetic field during the dephasing gradient with continuously higher precession frequencies in a positive (or counterclockwise) rotation. The rephasing gradient will cause protons to process at an even higher frequency because the moving protons will have reached an even higher gradient level by this time point in the sequence. However, the rephasing gradient will cause the protons to reverse their precession to a negative (clockwise) direction. Because the protons are now precessing at a higher frequency in tile opposite direction during the rephasing gradient compared with the dephasing gradient, at the time of gradient recalled echo, the moving protons will have a net phase. Proton phase shift is then calculated and translated into signal indicating both magnitude and direction.~-3

Proton phase shift is proportional to proton velocity in PC MRA. Flow-related enhancement is proportional to proton phase shift up to 180 °. A phase shift of greater than 180 ° will result in aliasing as it equates to a decreased phase shift in the opposite direction and therefore decreased flow-related enhancement with an incorrectly re- versed direction. Velocity encoding is a parameter in PC MRA that adjusts the strength of the bipolar gradients so that the phase shift does not exceed 180 ° . Velocity encoding is set to the maximum velocity within the vessel and is measured in cm/s. In normal patients, peak velocity is 63 + 4 crn/s in the carotid arteries, 51 + 4 cm/s in the basilar artery, and 69 + 9 cm/s in the middle cerebral artery. 4

MRA IN ACUTE STROKE 215

Fig. 3. Collateral flow. (A) Phase contrast map with right to left gradient demonstrates normal appearance. (B) Phase contrast map in patient with severe left ICA stenosis shows retrograde collateral flow across the anterior communicating artery and left A1 ACA (arrow).

Direction of blood flow relative to the bipolar gradient is calculated depending on whether the net phase shift is positive or negative. Blood flow in the direction of increasing gradients will result in a negative phase shift and vice versa. As a result, PC MRA not only shows vascular flow but also directionality as indicated by vascular hyperinten- sity or hypointensity to background. Assessment of flow direction is important when assessing collat- eral retrograde supply from anterior or posterior communicating arteries with severe ICA stenosis or when assessing subclavian steal phenomenon (Fig 3). Gradients in PC MRA are oriented in orthogonal directions to obtain 3 directional maps. Orthogonal maps are also combined to form an overall flow related enhancement map without directionality.

ceMRA

First-pass ceMRA involves performing a rapid 3D gradient echo sequence after a bolus of gado- linium. Repetition time (TR) of less than 10 ms is shorter than the T1 relaxation time of spins includ- ing fat and blood so that maximum background saturation is achieved. Intravascular gadolinium reduces the longitudinal relaxation time of proton spins to result in intravascular unsaturated spins and signal. Because ceMRA is not dependent on inflow enhancement, high vascular signal is

present even with turbulent flow at arterial sites of stenosis and bifurcation as well as in-plane flow. Short TR decreases motion artifact relative to nonenhanced MRA (neMRA) (Fig 4). 7

At Massachusetts General Hospital, a gadolin- ium bolus of 20 mL is power injected at a rate of 2 mL/s for ceMRA. Imaging must be accurately timed to occur during the first pass of the gadolin- ium bolus. Improper timing (scanning too early or too late) results in inadequate arterial enhance- ment, Scanning too late also results in venous enhancement obscuring the arterial enhancement. Arrival time of the bolus may be determined with a test bolus of 2 mL of gadolinium and a series of Tl-weighted acquisitions of the first slice of the imaging volume of interest. 5 Acquiring not only the ceMRA but also the center of k space during peak arterial enhancement is important because this is where low spatial frequency information controlling image contrast is stored. Time-resolved imaging of contrast kinetics is a technique in which sampling of the center of k space occurs during arterial enhancement and periphery beyond the enhancement window. 5-7

MIP

MIPs are a series of projections 360 ° around the imaging volume and usually in two orthogonal planes. Projections are then viewed in a cine loop

216 YU ET AL

Fig 4. String sign. (A) 2D TOF noncontrast MRA MIP shows severe segmental stenosis in the proximal left cervical ICA (arrow) in the same patient as in Fig 3B. {B) ceMRA also defines the stenosis and close inspection reveals tiny residual lumen (arrow).

to produce a pseudo-3D display of the vasculature. MIPs are created by first-stacking MRA imaging slices into a 3D volume. At each projection, parallel rays are cast through the 3D stack of slices, and the maximum pixel value along each ray is obtained to create a 2D projection image of max- imal intensity. 2 Segmenting out the nonvascular hyperintensity in each imaging slice before stack-

ing them into a 3D volume is a postprocessing step that creates MIPs with better arterial visualization as extra-arterial hyperintensity is eliminated.

MRA EVALUATION OF ACUTE STROKE

Typically, we evaluate the neck vessels from the arch to the skull base with ceMRA for the follow- ing reasons: (1) ceMRA is not susceptible to signal

MRA IN ACUTE STROKE 217

Fig 5. Complete occlusion. (A) 2D TOF nonconrast MRA MIP of the neck shows complete loss of flow-related enhance- ment beginning at the origin (arrow) and extending along the course of the right ICA. (B) 3D TOF MRA MIP of the circle of Willis shows complete loss of flow-related enhancement in the distal right ICA to its bifurcation (arrow) indicating com- plete occlusion or very slow flow. In this patient, there was occlusion by thrombus.

loss from turbulence, slow flow, nor in-plane flow compared with TOF and PC techniques; (2) ceMRA allows better vessel to background con- trast compared with TOF and PC techniques; (3) the lack of signal loss from saturation effects allows coverage of a larger region (arch to skull base) compared with TOF techniques; (4) ceMRA allows much shorter imaging times; and (5) with a short TR, ceMRA is less susceptible to motion artifact compared with TOF and PC techniques.

Because incorrect timing of imaging with re- spect to the contrast bolus may occur and the sequence cannot be repeated, we typically perform a 2D TOF MRA through the neck before the ceMRA. If dissection is of clinical concern, we perform fat saturated axial Tl-weighted images from C3 to the pons. This technique is sensitive for

detecting T1 hyperintense hematoma in the false lumen.

For the detection of ICA stenosis greater than 70%, ceMRA has a sensitivity of 93% to 94% and specificity of 85% to 100% compared with digital subtractive angiography (DSA) based on recent reports, l°,ll Sensitivity and specificity for neMRA is lower. Compared with DSA, 2D TOF has 85% sensitivity and 70% specificity for detection of stenosis greater than 60%, 12 and 3D TOF has an 88% to 98% sensitivity and 72% to 94% specificity for stenosis greater than 70% (Fig 5). l°,13

The relative low specificity of MRA for detect- ing clinically significant stenosis is related to apparent overestimation of the degree of stenosis. ceMRA eliminates overestimation of stenosis re- lated to turbulence causing intravoxel dephasing

218 YU ET AL

for neMRA. However, overestimation of stenosis

may result from artifactual loss of faint intralumi-

nal signal during MIP construction for MRA. In

addition, the greater number of projections avail-

able with MRA compared with DSA may provide

a more accurate estimate of nonconcentric stenosis

and result in an apparent overestimation of stenosis based on DSA as the gold standard.14

Although ceMRA techniques have resolved the

problems of signal dropout from intravoxe]

dephasing and saturation effects, they are not adequate to differentiate a string sign from occlu-

sion. If no flow-related enhancement is identified

within a vessel on a neck MRA, we typically

perform a computed tomography angiogram or

conventional angiogram to determine vessel pa-

tency. Typically, we evaluate the circle of Willis with

3D TOF MRA. This technique has better spatial

resolution compared with ceMRA and 2D tech-

niques and is much faster than 3D PC with a

similar spatial resolution. 3D is also preferred over

2D TOF for intracranial use because of its in-

creased signal to noise ratio and decreased signal

loss caused by in-plane flow.

In general, in the setting of acute stroke, there is

good correlation between intracranial ICA and

proximal MCA, anterior cerebral artery, and pos-

terior cerebral artery abnormalities identified on

MRA compared with angiography. Despite optimi-

zation of technique with short echo times, partial

echo sampling, small voxel size and flow compen-

sation, 3D TOF techniques tend to overestimate

stenoses in the region of the circle of Willis. The

carotid siphon is particularly problematic because

of the complex flow pattern in that region.

MRA techniques are not reliable for detecting

stenoses distal to the major branch points in the

circle of Willis. If vasculitis or distal atheroscle-

rotic lesions are suspected, we typically perform a

conventional angiogram. In acute stroke, in addi-

tion to the 3D TOF sequence, we perform a 2D PC

with 3 axial slabs, 10 mm thick, from the mid ports

to just above the sella. This sequence allows for

evaluation of collateral flow. For example, if a

carotid artery is occluded, we can evaluate for

reversal of flow in the posterior communicating

artery or in the A1 segment of the anterior cerebral

artery. If there is a midbasilar stenosis or occlu-

sion, we can evaluate for reversal of flow in the

distal basilar artery.

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