Imaging of Cardiac Perfusion 36

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A. Huber, MD

Department of Clinical Radiology, University Hospitals – Gross hadern, Ludwig Maximilian University of Munich, Marchioni nistr. 15, 81377 Munich, Germany

C O N T E N T S

36.1 Background 407

36.2 Pathophysiology of Myocardial

Perfusion 408

36.3 Pulse-Sequence Techniques 408 36.4 Parallel-Imaging Techniques 409 36.4.1 GeneRalized Autocalibrating Partially Parallel Acquisitions (GRAPPA) 409 36.4.2 TSENSE 409

36.4.3 Auto-SENSE 411

36.5 Parallel Imaging in the Clinical Assessment of Myocardial Perfusion 412

References 414

Imaging of Cardiac Perfusion 36

Armin Huber

36.1

Background

A decrease in myocardial perfusion represents the ﬁ rst effect of occluding coronary artery disease (CAD). It can be detected before clinical symptoms or left ventricular dysfunction become obvious (Nesto and Kowalchuk 1987). Therefore, the assessment of myocardial perfusion representing the functional relevance of coronary stenoses appears the most promising concept for a noninvasive test to detect early CAD. Imaging of myocardial perfusion is cur- rently dominated by nuclear-medicine techniques.

Single-photon-emission computed tomography (SPECT) using Thallium-201 or TC-99m sestamibi accounts for the majority of clinical studies, whereas positron emission tomography (PET), which must be

considered the standard of reference for perfusion imaging, is available only at specialized centers. For the detection of signiﬁ cant CAD, these techniques provide sensitivity and speciﬁ city values ranging between 83% and 95%, and 53% and 95%, respec- tively (Hannoush et al. 2003; Schwaiger and Melin 1999; Schwaigwer et al. 1994; Muzik et al. 1998;

Demmer et al. 1989). Furthermore, a wide range of clinical studies has documented an important prognostic signiﬁ cance for perfusion deﬁ cits detected by nuclear techniques (Iskander and Iskanderian 1998; Mansoor and Heller 1997). SPECT and PET do, however, have important limitations. These include attenuation artefacts, exposure to ionizing radiation, and poor spatial resolution, which do not allow the reliable detection of subendocardial perfusion defects (Wagner et al. 2003).

With recent hardware and software improvements, magnetic resonance imaging is emerging as an attrac- tive alternative to nuclear medicine techniques for imaging of myocardial perfusion. First-pass myocardial perfusion imaging is based on fast T1-weighted image sets collected during injection of an intra- venously administered contrast bolus resulting in enhancement of healthy myocardial tissue compared to the precontrast images. Although both MRI and nuclear medicine techniques can measure myocardial perfusion, important differences between both methods have to be considered. With Thallium-201 or TC-99m sestamibi SPECT, the signal intensity in the myocardium depends on the myocardial blood fl ow and the amount of viable cells extracting the tracer into the intracellular space. Therefore, areas with decreased myocardial perfusion as well as areas with a reduced number of viable cells result in reduced tracer uptake (Mansoor and Heller 1997; Ragosta and Beller 1993). In contrast, the myocardial signal intensity on MR images during fi rst-pass perfusion of a paramagnetic contrast agent depends on myocardial blood fl ow, vascular permeability, and the size of the extracellular space. The viability of myocardial cells does not affect signal characteristics. Thus, reperfused

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but infarcted myocardium appears dark on SPECT images, whereas it may be hypointense or hyperin- tense to normal myocardium on fi rst-pass MRI at rest. Accurate analysis of fi rst-pass perfusion studies requires profound knowledge of the MR hardware and software potential, the characteristics of paramagnetic contrast agents, and the pathophysiology of myocardial perfusion. In addition, it is necessary to keep in mind differences, advantages, and limitations of MR perfusion measurements with respect to other clinically available methods. This chapter explores the pathophysiologic background, recent technical developments, and current clinical status of fi rst-pass MRI of myocardial perfusion.

36.2

Pathophysiology of Myocardial Perfusion

Stenoses of an epicardial coronary artery lead to reduced perfusion and correspondingly diminished myocardial oxygen delivery. However, at rest, the equilibrium between perfusion, metabolism, and contractile function can be normal even in cases of moderate to severe stenoses. Therefore, these stenoses are clinically occult in perfusion studies at rest.

At stress, induced pharmacologically or by physical exercise, there is a three- to fourfold increase in contractile function accompanied by a fourfold increase in oxygen demand and perfusion (Bourdarias 1995;

Wilke et al. 1997). Whereas the fl ow in normal coronary arteries can be increased by vasodilation, moderate and severe stenoses become fl ow limiting, resulting in perfusion defi cits, wall motion abnormalities, and symptomatic angina. Therefore, different stress tests are clinically used to detect myocardial ischemia (Iliceto 1995). In the progression of ischemia, suc- cessive myocardial events occur. These are known as the cascade of ischemia (Nesto and Kowalchuk 1987) (Fig. 36.1). Initially, hypoperfusion can only be detected in the subendocardial layer of the myocardium (Bache and Schwartz 1982). Further reduction of the blood fl ow due to more severe stenoses leads to transmural perfusion defi cits. Progression of ischemia leads to diastolic, followed by systolic, wall motion abnormalities, which can be detected by stress echocardiography or dobutamine stress MRI (Nagel et al. 1999). Finally, electrocardiographic changes can be detected and typical symptomatic angina may occur. As perfusion abnormalities are

the fi rst step in this cascade of ischemia, direct visu- alization of these perfusion defi cits seems to be the diagnostic test of fi rst choice in patients with sus- pected CAD.

36.3

Pulse-Sequence Techniques

Since 1991, imaging of ﬁ rst-pass wash-in effects by the application of a bolus of extravascular contrast agents is possible using gradient-refocused-echo sequences (Schaefer et al. 1992; van Rugge et al.

1991). For successful examinations a magnetic fi eld strength of 1.5 T is necessary to achieve suffi cient signal-to-noise ratio (SNR) and contrast-to-noise ratios (CNR) as well as high-performance gradients to enable fast data acquisition with high spatial resolution. For fi rst-pass MR perfusion imaging of the myocardium contradictory requirements have to be fulfi lled to some degree: Suffi cient temporal resolution to image several slices in each, or at least every second, heartbeat in order to sample the fi rst pass of the contrast bolus is necessary. A temporal resolution with imaging of one slice position every heart beat allows for postprocessing with a semiquantitative or quantitative evaluation (Al-Saadi et al. 2000;

Jerosch-Herold et al. 1998). A temporal resolution with imaging of one slice every second heart beat allows for a visual evaluation (Ishida et al. 2003), not for semiquantitative or quantitative postprocessing.

High spatial resolution including an in-plane resolution of 3 mm is necessary to distinguish the sub-

Fig. 36.1. Ischemic cascade. Hypoperfusion is the ﬁ rst patho- logical change in the myocardium during development of coronary artery disease

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endocardial and subepicardial layers of the myocardium. A slice thickness of 8-10 mm is adequate for discrimination of different perfusion areas in rela- tion to the long axis of the heart. In order to cover the ventricular myocardium as completely as possible, at least four to six slices should be acquired. A nearly linear relationship between contrast dose and signal intensity is mandatory to image normal and ischemic regions of the myocardium with high contrast. To meet these goals, myocardial ﬁ rst-pass perfusion sequences make use of various magnetization preparation techniques. These include inversion recovery, saturation recovery, and partial or notch pulse saturation. The preparation pulses support the T1-contrast of the consecutive perfusion images, acquired with different, fast data readout methods like gradient echo imaging, echo-planar imaging (EPI), or steady- state free precession (SSFP) techniques (Fig. 36.2) (Fenchel et al. 2004; Schreiber 2002; Hunold et al.

2004; Koestler et al. 2004).

Figure 36.3 shows the diagram of a ﬁ rst-pass perfusion sequence using a nonselective saturation-recovery preparation. The combination of magnetization preparation and data readout is repeated as often as it ﬁ ts into the RR interval. To cover a maximum number of slices, the inversion time (TI) between the magnetization preparation and the data readout segment needs to be kept as short as possible.

However, TI plays an important role in determining SNR and CNR (Bertschinger et al. 2001). A short TI permits the collection of more slices per cardiac cycle, whereas a long TI improves SNR and CNR.

A possible solution is presented by a notch pulse saturation technique that combines a long TI with fast multislice data acquisition (Slavin et al. 2001;

Bertschinger et al. 2001) (Fig. 36.4). For data readout, different types of techniques can be used. Fol- lowing a magnetization preparation pulse, a series of gradient-recalled echoes is generated. Using, for example, 100 phase-encoding steps, the data acquisition per slice requires 100×TR. In contrast to standard gradient-echo techniques, which generate only one echo per excitation, segmented EPI sequences collect several echoes per excitation (Sakuma et al. 1999).

The advantage of this sequence is related to acquisition time, because the data acquisition time per slice amounts to only 25×TR for 100 phase-encoding steps and an EPI factor of 4.

The use of parallel imaging allows for reduction of the acquisition time required for the readout segment. However, the inversion time remains the same.

Without parallel imaging, the time for the inversion

preparation is similar to the acquisition time for the readout segment. Therefore, an acceleration factor of 2 reduces the time frame per slice only by 25%. In addition to the shorter scan time per slice, artefacts are reduced by the reduction of the acquisition time for the readout segment.

36.4

Parallel-Imaging Techniques

36.4.1

GeneRalized Autocalibrating Partially Parallel Acquisitions (GRAPPA)

In GRAPPA (Griswold et al. 2002), uncombined images without aliasing artefacts are reconstructed for each coil element in the array by generating the missing k-space lines for each coil element (cf.

Chap. 2). A Fourier transform can then be used to reconstruct the uncombined image for each coil. The set of uncombined images can be combined using a normal sum-of-squares reconstruction. Advantages of the GRAPPA algorithm for cardiac perfusion MRI are the integrated acquisition of the reference lines (auto-calibration signals) in the undersampled acquisition of k-space lines during the readout segment, which allows for reduction of the infl uence of motion artefacts and for an update of the coil sensitivity profi le for each time frame. Thus, there is an SNR loss within one frame as known for the use of parallel imaging; however, no additional SNR or CNR loss need to be expected for the signal change over time, which is important for accurate assessment and analysis of the signal-time curves during fi rst- pass for each myocardial segment (Fig. 36.5). A disadvantage compared to the TSENSE and auto-SENSE techniques discussed below is the additional need of acquisition time for the reference lines (Fig. 36.6).

The real (or effective) acceleration factor is reduced by the ratio of the number of additional reference lines and of totally acquired k-space lines (including the reference lines).

36.4.2 TSENSE

TSENSE is a fast imaging technique that can be used for a dynamic acquisition of images in the same slice posi-

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a

b

Fig. 36.2a,b. A 59-year-old woman with high-grade stenosis in the right coronary artery. Perfusion images acquired with a saturation-recovery TrueFISP sequence. The basal and mid- papillary slices show a perfusion defect in the inferior seg- ments under adenosine stress (arrow, ﬁ rst line). In addition, a subendocardial susceptibility artefact can be identiﬁ ed (arrowheads). Invasive coronary angiography reveals an oc- clusion of the right coronary artery (arrow)

tion (Kellman et al. 2001); a detailed description can be found in Chap. 12. In contrast to techniques such as GRAPPA or auto-SMASH and similar to auto-SENSE, no additional reference lines have to be acquired for reconstruction of full images after acquisition of only an undersampled part of the k-space lines per frame, e.g., of every other k-space line for an acceleration factor of R=2. Thus, a nominal acceleration factor of 2 results in a true shortening of the acquisition time per frame by a factor of 0.5 (Fig. 36.7).

36.4.3 Auto-SENSE

Auto-SENSE uses coil sensitivity information acquired during a series of dynamic scans for a SENSE reconstruction (Koestler et al. 2003). By interleaving the acquisition of different undersampled parts of the k- space from a subset of the dynamic series where no changes occur, a full k-space data set can be generated to extract coil sensitivity information. When the

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Fig. 36.5. One image of a dynamic series of 60 images acquired during ﬁ rst pass of the contrast agent is shown. The endocardial and epicardial contours allow deﬁ ning the left-ventricular myocardium. In each of six segments a signal-time curve is calculated by plotting the signal intensity values over the time-point of acquisition. The signal-time curves allow determining semiquantitative perfusion parameters like upslope, maximum signal and area-under-curve

Fig. 36.3. Non-selective saturation-recovery preparation. An inversion time (dotted line) of about 100 ms is necessary for adequate preparation of the T1 contrast. No data acquisition is possible during the inversion time. The number of slices is limited by the length of the RR interval and the length of the inversion time and the read-out segment

Fig. 36.4. Notch pulse saturation with a slice-selective satura- tion pulse allows for acquisition of one slice during preparation of another slice. A higher number of slices can be acquired during one RR interval with an identical inversion time (dot- ted line) compared to a non-selective preparation

patient can hold the breath for the dynamic acquisition of the perfusion images, the whole series can be used to determine the coil sensitivities. Since no additionally acquired lines in k-space are necessary in auto-SENSE, the full maximum acceleration factor of SENSE can be reached. In contrast to conventional SENSE imaging, a separate prescan to determine the coil sensitivity proﬁ les is not needed with auto-SENSE. Thus, auto- SENSE combines the advantages of the self-calibrating

and traditional calibration methods: the elimination of motion-related miscalibration and achievement of the full maximum acceleration factor.

Auto-SENSE has been reported to be more robust for heart perfusion imaging than alternative approaches such as UNFOLD or TSENSE. Image artefacts such as those presented by Madore (1999) or Kellman et al. (2001) for SENSE reconstruction were not noticed in the study of Koestler et al. (2003),

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possibly because of the improved determination of coil sensitivity information particularly in the lungs.

Due to the accelerated image acquisition compared to commonly used turbo-FLASH sequences (Wilke et al. 1997; Jerosch-Herold et al. 1998) without parallel imaging, auto-SENSE heart perfusion imaging allows a complete coverage of the human heart with a single contrast-agent administration.

36.5

Parallel Imaging in the

Clinical Assessment of Myocardial Perfusion

Reports in the literature for evidence of superiority of parallel imaging concerning the diagnostic accuracy for detection of coronary artery stenoses or occlusions or for the assessment of the hemodynamic relevance of intermediate lesions are still limited, especially in larger

patient populations with correlation of MR perfusion results with coronary angiography, scintigraphy or PET. The GRAPPA technique seems to be most promising in preserving the contrast change from frame to frame, which is important for the detection and accurate assessment of the short upslope segment of the signal-time curve from the foot-point to the signal maximum. The introduction of the GRAPPA technique may improve the diagnostic accuracy for a visual assessment of the images as the number of myocardial segments with susceptibility artefacts is reduced from 15% to 5% by this technique (Figs. 36.8-10) (Hubert et al. 2006). The most important disadvantage of the GRAPPA technique is that the additional acquisition of reference lines is time consuming. Usually 12 to 24 reference lines have to be acquired.

In contrast to the GRAPPA technique, both auto- SENSE and TSENSE do not require acquisition of additional k-space lines. Thus, the theoretical acceleration factor of, e.g., 2 can be used. However, there may be a loss of contrast sharpness for image contrast change from frame to frame by temporal smearing (Fig. 36.11). This may be a problem for the auto-SENSE (Madore et al. 1999) and the TSENSE technique (Kellman et al. 2001).

The readout technique of choice for the use of parallel imaging is probably the gradient-echo readout. The gradient-echo EPI hybrid technique causes more noise and in the combination with parallel imaging, which causes an additional SNR loss, the gradient-echo EPI- readout technique can be expected to be inferior. The SSFP technique allows for achieving a higher SNR and CNR per frame (Fenchel et al. 2004; Schreiber 2002;

Hunold et al. 2004), however, the linearity of contrast agent concentration and signal intensity in the myocardium (Koestler et al. 2004) is inferior compared to gradient-echo techniques. Therefore, hypoperfused areas can appear bright in spite of a low contrast agent concentration in the myocardium. Thus, an evaluation by eye-ball may underestimate pathological ﬁ ndings when an SSFP readout technique is used.

Fig. 36.6. Parallel imaging with an acceleration factor R=2 and integrated acquisition of reference lines. Every second k-space line is acquired. In addition reference lines (dashed lines) are acquired to estimate the coil sensitivity proﬁ les

Fig. 36.7. The even k-space lines are acquired during the 1st, 3rd and n-th RR interval. The odd lines are acquired during the 2nd, 4th and (n+1)-th RR interval. From two frames, a full k-space information can be obtained

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Fig. 36.8. A 62-year-old man with suspicion of coronary artery disease. Three short-axis images were acquired with a saturation-recovery turboFLASH pulse sequence without parallel imaging. The ﬁ rst line shows images that were acquired during adenosine infusion. The images in the second line were acquired at rest. The dark subendocardial rim (arrow) is a typical susceptibility artefact. No perfusion defect can be identiﬁ ed

Fig. 36.9. A 71-year-old man with suspicion of coronary artery disease. Four short-axis images were acquired with a saturation- recovery turboFLASH pulse sequence with parallel imaging (acceleration factor R=2). The ﬁ rst line shows images which were acquired during adenosine infusion. The images in the second line were acquired at rest. The dark area in the anterolateral and inferolateral segment (arrowhead) is caused by a perfusion defect, which is visible during adenosine stress, not at rest. A susceptibility artefact cannot be identiﬁ ed

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