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J Am Coll Cardiol, 2005; 46:542-551, doi:10.1016/j.jacc.2005.05.065 (Published online 14 July 2005).
© 2005 by the American College of Cardiology Foundation
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YEAR IN CARDIOLOGY SERIES

The Year in Cardiac Imaging

Raymond J. Gibbons, MD*,* and Philip A. Araoz, MD{dagger}

* Division of Cardiovascular Diseases and Internal Medicine, Department of Medicine, Rochester, Minnesota
{dagger} Division of Cardiovascular Diseases and Internal Medicine, Department of Radiology, Mayo Clinic and Mayo Foundation, Rochester, Minnesota

Manuscript received May 26, 2005; accepted May 31, 2005.

* Reprint requests and correspondence: Dr. Raymond J. Gibbons, Mayo Clinic, Gonda 5, 200 First Street, SW, Rochester, Minnesota 55905 (Email: gibbons.raymond{at}mayo.edu).

In this sequel to our report last year, we have again attempted to highlight the most important recent literature in single-photon emission computerized tomography (SPECT) myocardial perfusion imaging, cardiac positron emission tomography (PET), cardiac computerized tomography (CT), and cardiac magnetic resonance imaging (MRI). In almost all cases, these studies were published between May 31, 2004, and April 30, 2005, in the English-language literature. We have once again had to arbitrarily include some articles and exclude others in the interest of space. We apologize to those whose work we excluded or inadvertently overlooked. The selection of the best literature in any given year is certainly an inexact judgment. We have again organized this summary of the literature around topical themes in an attempt to encourage the reader to think as broadly as possible about the application of imaging to clinical problems.


   Technical advances
Top
 Technical advances
Myocardial viability
 Cardiac Resynchronization...
 CAD
 LV Function
 Molecular imaging
 Conclusions
 References
 
SPECT.   Despite the maturity of SPECT imaging, important technical advances continue. Hatada et al. (1) reported on the use of a new technetium perfusion agent (N-DBODC5) in a rat model. The agent cleared rapidly from the blood pool and had much more rapid liver clearance than either sestamibi or tetrofosmin, suggesting that it may offer the potential for earlier imaging acquisition and less interference from hepatic uptake.

Abidov et al. (2) described the use of an automated method to detect transient ischemic dilation in patients undergoing adenosine myocardial perfusion imaging. Patients with an abnormal automated transient ischemic dilation ratio, first established in a pilot group and then tested in the validation group, were more likely to have severe and extensive coronary artery disease (CAD).

Dupuis et al. (3) described a pilot study of a highly novel method to quantify hyperemic forearm blood flow response during resting myocardial perfusion imaging using tetrofosmin. The ratio of the maximum upslope in the two arms had modest sensitivity and specificity for the detection of CAD but potentially offered an adjunctive measurement that could easily be added to existing imaging protocols.

Fricke et al. (4) examined 140 patients who underwent sestamibi SPECT imaging with attenuation correction using X-ray tomography. A total of 27 patients had pronounced defects in the apical or anterior wall after attenuation correction. Fricke et al. (4) examined these images carefully for misalignment in the Y-direction. With correction of the misalignment, 21 of the 27 defects improved, and 6 resolved completely. Berman et al. (5) carefully derived and validated a conversion algorithm to convert 20-segment perfusion scores to 17-segment perfusion scores. This conversion model will be of considerable interest to investigators.

MRI.   The major recent advance in MRI has been the introduction of 3-T scanners. These scanners were introduced by the vendors in 2002 for clinical use and theoretically are capable of producing twice as much signal as conventional 1.5-T scanners. Some preliminary studies have attempted to use that increased signal to image the coronary arteries (6,7), although these were early technical articles performed in volunteers. As is typically the case with MRI, application of the new technology is being widely applied in neuroimaging, which is the easiest organ system to image with MRI. Cardiovascular applications will likely follow.

Another area of technological advance has been MRI-guided interventions. Last year, several groups developed new technology that should make MRI-guided interventions closer to a clinical reality. Rieke et al. (8) developed an X-ray-compatible radiofrequency coil that would allow a patient to have the radiofrequency coil placed over the anatomy of interest while a fluoroscopic procedure was performed, which would make combined fluoroscopic/MRI equipment more feasible. Kuehne et al. (9) placed resonant circuits on stents, which were implanted in large vessels in animals. The resonant circuits allowed MRI visualization of the stents, which has previously been difficult with MRI. In a similar vein, Quick et al. (10) developed a wireless method for catheters to emit signal detectable by MRI.

CT.   Technical advances in CT have been very rapid. Since 1998, a new generation of scanner has been introduced every two years. Each generation of scanner has been marked by an increase in the number of detector rows, which has led to faster acquisitions and better spatial resolution. In 2002, the 16-detector row CT scanner became available. This scanner showed acquisition times fast enough to allow for coronary imaging in very cooperative patients with very slow heart rates. The coronary imaging produced with these scanners is not robust because it is successful only in select patients, but it has sparked a dramatic increase in the literature examining coronary computed tomography angiography (CTA), which is described in the sections that follow. The vendors introduced the 64-detector scanner in the fall of 2004. Although all of last year’s literature discussed the use of the 16-detector scanner, it is expected that next year’s literature will be dominated by new studies performed with the 64-detector scanners. However, although the 64-detector scanner is still brand new, there are reports in the literature about possible new scanners, at least of one which may use a flat-panel detector (11).


   Myocardial viability
Top
 Technical advances
 Myocardial viability
Cardiac Resynchronization...
 CAD
 LV Function
 Molecular imaging
 Conclusions
 References
 
SPECT.   Bax et al. (12) demonstrated the impact of severe left ventricular (LV) dilation on functional recovery after revascularization in patients with viable myocardium by SPECT 18F-deoxyglucose (FDG) imaging. The change in ejection fraction after revascularization was linearly related to baseline LV end-systolic volumes. Event rates during follow-up depended on both viable myocardium and LV size.

Slart et al. (13) compared resting tetrofosmin SPECT and FDG SPECT in 33 patients with CAD (CAD) and LV dysfunction. Of those segments judged viable on FDG SPECT, 89% were classified as viable by tetrofosmin SPECT. With attenuation correction, this percentage increased to 96%.

PET.   Rizzello et al. (14) published long-term follow-up in 66 patients with ischemic cardiomyopathy who underwent revascularization. Most patients with viable myocardium by PET had an increase in LV ejection fraction 12 months after surgery. Of those patients with an increased ejection fraction at 1 year, 93% had persistent improvement at 4.5 years.

Hernandez-Pampaloni et al. (15) studied 116 patients with ischemic cardiomyopathy and ejection fraction ≤40% by PET. Of 834 dysfunctional segments, 72% demonstrated chronic stunning and only 9% demonstrated hibernation, suggesting that chronic stunning is far more prevalent than generally realized.

Santana et al. (16) studied 90 patients with a mean ejection fraction of 26% and LV dysfunction due to CAD by gated FDG PET. End-diastolic volume and end-systolic volume assessed by PET both had greater prognostic value than the ejection fraction. Patients with marked LV dilation showed less improvement in heart failure symptoms with revascularization.

MRI.   The most widely used MRI method for measuring viability is one in which the patient is imaged approximately 10 min after the injection of MRI contrast material. The contrast washes out of normal myocardium but remains in the interstitial space of infarcted myocardium so that the infarcted tissue displays "delayed enhancement" and appears bright.

Although this technique is widely accepted, most of the literature regarding delayed enhancement is based on animal models or on chronic infarctions in humans. Several studies compared MRI delayed enhancement in the acute myocardial infarction (MI) setting to peak biochemical markers (17–20), nuclear medicine SPECT techniques (18,19,21), or functional assessment (Table 1) (20). They reported generally good correlations with the different reference standards, suggesting that delayed enhancement MRI has potential as a surrogate outcome measure of infarct size.


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  		Table 1. Papers Evaluating MRI Delayed Enhancement in the Setting of Acute MI
 
CT.   In contrast to SPECT, PET, and MRI, viability with CT is in a very developmental stage. Because CT contrast material is cleared by the same mechanisms as MRI contrast material, a CT "delayed-enhancement" approach is possible. In 58 patients studied at 2 days, 28 days, and 1 year after MI, Koyama et al. (22) found CT-delayed enhancement in 36 (62%) of the patients. Wall thickening at follow-up was significantly less for patients with this finding than for those without. Although this study was limited by small patient numbers and the lack of a gold standard, it suggested that a delayed enhancement technique might be applicable with CT.


   Cardiac Resynchronization Therapy (CRT)
Top
 Technical advances
 Myocardial viability
 Cardiac Resynchronization...
CAD
 LV Function
 Molecular imaging
 Conclusions
 References
 
PET.   Lindner et al. (23) compared 31 study patients with severe dilated cardiomyopathy and left bundle branch block with 14 control patients who had mild-to-moderate dilated cardiomyopathy without left bundle branch block. The patients showed a heterogeneous distribution of both MVO2 and myocardial blood flow, both of which were increased in the lateral wall. The control group did not show these differences.

Knuuti et al. (24) studied the right ventricle in 10 patients with idiopathic dilated cardiomyopathy who had undergone CRT. They reported a significant correlation (R = –0.66, p = 0.03) between Kmono in the right ventricle and LV stroke volume response to CRT, as well as an increase in right ventricular oxidative metabolism with CRT during dobutamine-induced stress.

O’Neill et al. (25) examined 44 patients with nonischemic dilated cardiomyopathy. Evidence of scarring was found, using PET, in 91% of the patients, involving a mean of 25% of the LV, predominantly in the left anterior descending artery distribution. The QRS duration correlated positively with the degree of scarring. The authors suggested that cardiac resynchronization therapy might be less effective in the presence of such scarring and suggested the need for further studies.

MRI.   There is a small-but-growing amount of literature suggesting that MRI might be safely performed on patients with pacemakers. Few studies have examined the safety of implantable cardioverter defibrillators (ICDs) in an MRI environment. To fill this gap, Roguin et al. (26) studied 17 ICD and 9 pacemaker models both in vitro (in gel phantoms) and in vivo (in dogs). They evaluated the different devices for heating, force exerted by the magnetic field, and function after scanning.

Although they found some lead-tip heating and some force acting upon the devices, the authors felt these were not significant for pacemakers and for ICDs manufactured after the year 2000. Because ICDs interpreted the magnetic field as an arrhythmia, the authors suggested, ICDs should be set to "monitor-on/therapy-off" mode during MRI. Several ICD models were irreversibly damaged and could not be subsequently interrogated. Finally, there were minor battery, parameter, and memory changes in some of the remaining ICDs. They recommended that models that were damaged or underwent even minor battery changes should not undergo MRI.

In contrast to ICDs, they found that the MRI field did not modify function for pacemakers. They concluded that MRI of the pacemakers studied was safe, although they recommended setting pacemakers to VOO for pacemaker-dependent patients and to ODO for nondependent patients. Nevertheless, the authors cautioned that their findings might not be completely applicable in humans and applied only to the ICD and pacemaker models studied.


   CAD
Top
 Technical advances
 Myocardial viability
 Cardiac Resynchronization...
 CAD
LV Function
 Molecular imaging
 Conclusions
 References
 
Diagnosis.   SPECT
Danias et al. (27) used gated SPECT imaging to identify underlying CAD in 164 patients with an ejection fraction of ≤40%. The combined assessment of perfusion, reversibility, and regional wall motion had a relatively high sensitivity of 94% but a poor specificity of only 45%. A negative SPECT study might therefore eliminate the need for coronary angiography.

Hauser et al. (28) carefully examined the relationship between ST-segment depression during exercise and the magnitude of myocardial ischemia by SPECT imaging in 1,006 patients. The magnitude of ST-segment depression, the number of leads with ST-segment depression, and the occurrence of ST-segment depression at a low exercise workload were all highly associated with the magnitude of ischemia assessed by the summed stress score, confirming that ST-segment depression is caused by ischemia.

Akinboboye et al. (29) studied bicycle and mental stress testing in 58 patients with CAD. Mental stress ischemia was more frequent in patients with severe LV dysfunction than in those with normal LV function, suggesting that mental stress may be of particular importance in patients with LV dysfunction.

Aboul-Enein et al. (30) examined the impact of collaterals in patients with single-vessel chronic total occlusion and no previous MI. Resting wall motion abnormalities were more frequent in those with poor collaterals. Severe and extensive stress SPECT perfusion defects were similar in patients with excellent collaterals and poor collaterals. Resting perfusion was near-normal in both groups, indicating that wall motion abnormalities were likely due to chronic stunning rather than hibernation.

Mowatt et al. (31) reported a systematic review of the effectiveness and cost-effectiveness of myocardial perfusion imaging for CAD for the United Kingdom National Health Service. This extensive, lengthy document emphasized the need for further research regarding both gated and attenuation-corrected SPECT.

PET
Mishra et al. (32) carefully examined the relationship between changes in myocardial blood flow as assessed by N-13 ammonia with PET and changes in heart rate and blood pressure during adenosine infusion. The change in heart rate and change in blood pressure were extremely poor predictors of coronary flow reserve; the greatest correlation coefficient was only R = 0.11. Thus, the common practice of using heart rate and blood pressure to assess adenosine response is ill-advised (Fig. 1).



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  		Figure 1 Correlation between change in heart rate and change in blood pressure during adenosine with changes in myocardial blood flow assessed by N-13 ammonia. From Mishra et al. (32).

 
Chow et al. (33) demonstrated the feasibility of exercise rubidium PET imaging. Compared with dipyridamole stress, exercise image quality was superior.

MRI: functional detection of CAD
With MRI, perfusion imaging and wall motion assessment can be performed in the same examination, as Paetsch et al. (34) reported in a study of 79 patients referred for clinically indicated cardiac catheterization. Before catheterization, these patients underwent a complex MRI examination, which included adenosine stress perfusion imaging, rest wall motion imaging, adenosine stress wall motion imaging, and high dose dobutamine stress wall motion imaging, which all were performed in the same examination. Cardiac catheterization was the gold standard, with any 50% or greater stenosis being considered a positive result.

Dobutamine stress wall motion assessment had the best sensitivity and accuracy, both of which were significantly better than adenosine perfusion (Fig. 2). Although stress echocardiographers might find these results encouraging, it is unclear whether the findings in this study might translate to other modalities.



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  		Figure 2 Sensitivity and specificity of perfusion and wall motion parameters obtained from a single magnetic resonance imaging examination. Dobutamine stress wall motion assessment had the best diagnostic performance. Open bars = sensitivity; solid bars = specificity. From Paetsch et al. (34).

 
CT: coronary calcium scanning
Two articles investigated the relationship between atherosclerotic burden as detected by CT coronary calcium scanning and myocardial perfusion abnormalities as detected by SPECT. Anand et al. (35) studied 220 asymptomatic patients with moderate-to-severe amounts of coronary calcium (Agatston score ≥100), who all underwent SPECT myocardial perfusion imaging. They discovered that SPECT was abnormal in 18% of patients with moderate levels of calcium (scores ranging from 100 to 399) and in 45% of patients with severe levels of calcium (scores ≥400).

Berman et al. (36) retrospectively studied 1,195 patients who underwent both CT coronary calcium scanning and myocardial perfusion scanning for clinical indications. In contrast to the study by Anand et al. (35), Berman et al. included patients with low scores and patients with symptoms (49% of the study group). Berman et al. reported a lower frequency of abnormal scans: 2% of patients with mild levels of calcium (scores <100), 5% of patients with moderate levels of calcium (scores ranging from 100 to 399), 9% of patients with more severe scores (400 to 999), and 20% of patients with the most severe scores (≥1,000) (Fig. 3).



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  		Figure 3 Frequency of ischemic single-photon emission computerized tomography myocardial perfusion scan (open bars) and of a moderately-to-severely ischemic scan (solid bars) for patients divided into six groupings based on the coronary artery calcium (CAC) score. From Berman et al. (36).

 
Anand et al. (35) suggested that clinicians should consider both the calcium score and clinical parameters before referring patients to perfusion imaging. However, Berman et al. (36) concluded that perfusion imaging generally is not indicated for patients with a coronary calcium score <100 and that clinical parameters have the most impact on the decision to proceed with perfusion imaging for patients with scores ranging from 100 to 400. Both authors felt that high calcium scores (>400) warranted consideration for myocardial perfusion scanning.

CT: noninvasive angiography
The most recent generation of scanner, the 16-detector scanner introduced in 2002, has made coronary CTA feasible in select patients. In Table 2, we list the studies to date comparing 16-detector coronary CTA with cardiac catheterization. We have only included studies that were prospective and in which 16-detector coronary CTA was performed before cardiac catheterization (37–46).


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  		Table 2. 16-Detector Computed Tomography Coronary Angiography Versus Catheter Coronary Angiography
 
Although many of the studies excluded segments that were considered not analyzable, overall the results are encouraging; coronary CTA appears to have high specificity and good negative predictive value (Fig. 4A). However, some caveats are in order.



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  		Figure 4 (A) True-positive 16-detector coronary computed tomography angiography (CTA). (a) Axial images show a calcified and uncalcified plaque in the proximal left anterior descending (LAD) (arrow). (b) A cross section through the plaque shows calcium on the periphery and a low-attenuation, soft plaque obstructing much of the lumen (arrow). A small residual lumen with contrast is visible at approximately the one-o’clock position in the vessel lumen. The axial image is overlaid in the lower left-hand corner and the plane of the cross section is shown (line). (c) Catheter angiography shows an eccentric stenosis (75% diameter, arrow) corresponds to the plaque observed at CT. From Ropers et al. (38). (B) False-positive 16-detector coronary CTA. (a) A multiplanar reformat of the CT data, intended to display the LAD in a projection equivalent to a right anterior oblique projection at catheter angiography. Extensive calcification can be found along the course of the LAD artery. Proximally, there is a heavily calcified plaque, which is shown bisected with a white line. (b) A cross section of the vessel (the plane defined by the line in a). The cross section is entirely white, meaning it appears the vessel lumen is completely replaced with calcified plaque. (c) A catheter angiogram. At the site of the calcified plaque shown in (a) and (b) (line bisecting the LAD), there is mild stenosis but not the occlusion, as shown on the CT images from (a) and (b). For technical reasons, calcium appears to occupy more space on CT scans than it does in reality. For this reason, stenosis caused by calcified plaques is overestimated by CT. From Hoffmann et al. (40).

 
First, a low burden of coronary calcium is important for diagnostic images. For a variety of technical reasons, calcium appears to occupy an artifactually large space on CT images (Fig. 4B). For this reason, calcium outside the lumen may appear to cause a stenosis, and most reports cite coronary calcification as a major source of false-positive results. Because coronary calcium increases with age, it is important to note that all of the studies enrolled relatively young patients.

Second, low heart rates are required for diagnostic images. In all of the studies, patients were given beta blockers to slow the heart rate, and in one study (45) patients with heart rate >65 beats/min were excluded. Despite the low heart rates in these studies, image blurring was still a limiting factor, especially in the right coronary artery (42).

Third, the examination requires a cooperative patient who can hold his or her breath. All of the studies listed used clinically stable patients. Mollet et al. (39) required an adequate breath-hold as an inclusion criteria. Kuetner et al. (41) excluded one patient because the patient did not perform an adequate breath-hold during scanning. Given these caveats, CT may prove to be less useful in the highest risk patients—the elderly, the unstable, the uncooperative—and may be most useful in a lower risk group.

Prognosis.   Single-photon emission computerized tomography
Elhendy et al. (47) demonstrated the prognostic significance of peri-infarction ischemia in 345 patients with previous MI. Peri-infarction ischemia was a surprisingly better prognostic indicator than remote ischemia.

Liao et al. (48) reported on 997 patients who underwent exercise SPECT imaging and also had first-pass ejection fraction measured at peak exercise. They evaluated the prognostic power of the Duke treadmill score, peak ejection fraction, and the summed stress score. Although each of the three parameters was univariately significant, in clinical risk-adjusted models, first-pass ejection fraction was clearly superior to either the treadmill score or summed stress score for the prediction of cardiovascular death.

Azarbal et al. (49) reported on the potential prognostic value of chronotropic incompetence in patients undergoing exercise SPECT. The percent heart rate reserve achieved added to the severity of SPECT abnormality in the prediction of cardiac death. The authors concluded that this parameter should be incorporated into routine clinical reporting and risk stratification algorithms.

Navare et al. (50) reported a meta-analysis of 14,918 patients from 24 studies evaluating the prognosis of patients studied with either pharmacologic or exercise stress SPECT. The analysis showed higher annual event rates in patients with normal images after pharmacologic stress (1.78%) compared with exercise stress (0.65%). They also reported higher event rates with abnormal tests after pharmacologic stress compared with exercise stress. These differences appeared to reflect the different intrinsic risk of the two patient populations.

Hachamovitch et al. (51) derived and validated an algorithm for predicting cardiac death after adenosine SPECT. Their models, including age, percent ischemic myocardium by SPECT, percent fixed myocardium by SPECT, dyspnea, rest heart rate, peak heart rate, and resting electrocardiogram (ECG) abnormalities, suggested the importance of all of these parameters in test interpretation.

Special patient groups.   Acute chest pain triage
Kapetanopoulos et al. (52) reported on 341 diabetic patients in a substudy of the Emergency Room Assessment of Sestamibi for the Evaluation of Chest Pain (ERASE Chest Pain) trial. Acute triage of chest pain using resting myocardial perfusion imaging appeared to be just as effective in diabetic patients as in nondiabetic patients.

Kaul et al. (53) reported the results of a multicenter study employing contrast echocardiography and gated SPECT in acute chest pain assessment in 205 patients. Both imaging studies offered diagnostic and prognostic information that was incremental to clinical and electrocardiographic assessment.

Diabetes mellitus
Wackers et al. (54) reported baseline findings from the Detection of Ischemia in Asymptomatic Diabetics (DIAD) study. In 522 patients randomized to stress testing, 113 patients (22%) had silent ischemia, including 83 with SPECT perfusion defects, of whom 33 had moderate or large perfusion defects. This study added to the growing evidence of silent CAD in middle-aged diabetics.

Rajagopalan et al. (55) reported clinical and laboratory correlates of high-risk SPECT scans in 1,427 asymptomatic patients with diabetes. High-risk scans, which occurred in 18% of the patients, were associated with seven different variables on multivariate analysis, the most important of which were ECG Q waves and peripheral arterial disease.

Resting ECG abnormalities
Kwok et al. (56) demonstrated the incremental prognostic value of exercise thallium-201 SPECT in 939 patients with nonspecific ST- and T-wave abnormalities on their resting ECG. Most of the incremental prognostic value of SPECT was in those patients who were classified as intermediate-risk on the basis of clinical and exercise ECG parameters.

Elderly patients
Schinkel et al. (57) demonstrated the prognostic value of dobutamine tetrofosmin SPECT in 272 patients older than 65 years of age. Abnormal scan findings added significantly to clinical data, and identified low-risk and high-risk subsets. Valeti et al. (58) examined 274 patients 75 years or older with exercise thallium-201 SPECT. The summed stress score by SPECT classified most patients into useful low- and high-risk categories and was much more effective than the Duke treadmill score.

Monitoring of therapy.   Tio et al. (59) carefully studied 35 patients with end-stage CAD who were randomized to therapy with vascular endothelial growth factor, endomyocardial laser therapy, or conventional medical therapy. Using quantitative N-13 ammonia PET imaging, stress perfusion improved in the ischemic area with vascular endothelial growth factor therapy. Most noteworthy in this study was the ability to demonstrate a therapeutic benefit in a very small number of patients.

Mahmarian et al. (60) described the design and baseline characteristics of the Adenosine Sestamibi SPECT Post-Infarction Evaluation (INSPIRE) trial, a randomized, prospective multicenter trial using sestamibi SPECT for risk assessment after acute MI. Dobert et al. (61) examined myocardial perfusion with both PET and SPECT in 15 patients who received intracoronary bone marrow derived cells and 11 patients who received intracoronary blood-derived endothelial progenitor cells after MI. They demonstrated an increase in signal intensity in the infarct zone by both PET and SPECT, but there were no controls in this study.


   LV Function
Top
 Technical advances
 Myocardial viability
 Cardiac Resynchronization...
 CAD
 LV Function
Molecular imaging
 Conclusions
 References
 
SPECT.   Liu et al. (62) performed an extensive phantom and patient validation of a new quantitative method for gated SPECT. Their technique showed very close agreement (R = 0.90; SEE = 6.2%) with ejection fraction measured by equilibrium radionuclide angiography.

MRI.   Although different types of cardiac function are measurable with MRI, notably flow measurements in large vessels, the main functional assessment performed with MRI is the measurement of cardiac volumes. In much of the literature involving both MRI and cardiac volumes, MRI is now used as a gold standard against which other methods were measured. Last year, MRI was used in this manner in studies of three-dimensional echocardiography (63), contrast echocardiography (64), and CT (discussed in the following section).

One limitation of MRI for cardiac volumes is that the procedure is relatively slow. Currently, the acquisition of each anatomic level typically requires a separate breath-hold. Coverage of the whole heart usually takes 10 to 12 breath-holds, which may be difficult for some patients. A faster, near real-time acquisition would be desirable. In a small study, Peters tested such an acquisition (65). In 10 healthy volunteers they performed the standard, multibreath-hold acquisition and a novel, faster single breath-hold acquisition. Using Bland-Altman analysis, the mean difference in LV ejection fraction between the techniques was small (0.6%), although the 95% confidence intervals of this difference were considerable (±7.7%).

CT.   The main limitation of CT for functional imaging is that a bolus of contrast is required to distinguish the myocardium from the ventricular cavity. This bolus usually is visible for only a minute; therefore, all the required data must be acquired in that time. Unlike SPECT, PET, and MRI, which can use many beats to acquire images, CT requires extremely fast acquisitions.

These types of acquisitions are just recently becoming available. Five studies compared LV volumes, measured by 16-detector CT, to a gold standard (Table 3) (66–70). The initial results look very good, with excellent correlation coefficients and mean differences between CT and the gold standard, which were consistently <2%.


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  		Table 3. 16-Detector Computed Tomography for Left Ventricular Ejection Fraction
 

   Molecular imaging
Top
 Technical advances
 Myocardial viability
 Cardiac Resynchronization...
 CAD
 LV Function
 Molecular imaging
Conclusions
 References
 
As we indicated last year, the numerous papers in this field covering an enormous range of topics are well beyond the scope of this article. We have again chosen a few articles as examples of this rich literature.

PET.   Wu et al. (71) demonstrated the feasibility of molecular imaging with microPET in a rat model to monitor angiogenic gene expression with PET reporter genes. Cardiac transgene expression peaked at one day and declined over the next two weeks. The in vivo PET reporter gene expression correlated closely with ex vivo gamma counting as well as myocardial tissue enzyme activity.

Miyagawa et al. (72) compared two approaches to PET reporter gene imaging, a wild-type herpes simplex virus type 1 thymidine kinase (HSV1-tk) gene labeled with an iodine-124 iodouracil and a mutant HSV1-tk gene labeled with a fluorine-18-labeled guanine. The fluorine-labeled reporter gene appeared to be superior on the basis of continuous accumulation over time and a better imaging contrast.

MRI.   To date, most MRI-based molecular imaging methods use one of two approaches: cell labeling with iron, and antibody labeling with nanoparticles. In the cell-labeling method, iron (which is detectable by MRI) is phagocytized into cells, usually stem cells, which are then tracked. The use of this method is rapidly increasing because the iron particles are commercially available and the labeling procedure is not difficult. One study was an excellent example of careful cell labeling methods, even though the authors did not study the cardiovascular system (73). Bos et al. (73) carefully described the iron content per cell and how iron loading affected cellular proliferation and differentiation. The authors studied the in vitro relationship between cell concentration and MRI signal, showed the time course of uptake of the cells, and validated their results with histology.

In the antibody method, investigators create a particle (often called a nanoparticle) that binds to a target of interest and also gives off a detectable signal. Compared with phagocytotic cell labeling, nanoparticle creation is very difficult. However, once created, nanoparticles may contain many, sometimes thousands, of signal-generating components and also can be specifically targeted. For example, in an early, technical communication, Frias et al. (74) reported the creation of a high-density lipoprotein-like nanoparticle that could contain either 15 to 20 particles of MRI contrast material or fluorescent phospholipids (74). Kelly et al. (75) created a particle that targeted vascular adhesion molecule-1, which contained both MRI contrast agents and fluorescent particles. Using this particle, they were able to detect this particle in atherosclerotic plaques in an animal model.


   Conclusions
Top
 Technical advances
 Myocardial viability
 Cardiac Resynchronization...
 CAD
 LV Function
 Molecular imaging
 Conclusions
References
 
We hope that this review has successfully highlighted some of the most important new literature in cardiac imaging and stimulated you the reader to examine at least a few of the original articles in detail.


   Footnotes
 
Dr. Gibbons’ current research grants include: Radiant Medical, Boston Scientific, Boehringer Ingelheim, Spectranetics, KAI Pharmaceuticals, TargeGen, and TherOx. He is also a consultant for CV Therapeutics, King Pharmaceutical, Hawaii Biotech, Cardiovascular Clinical Studies (WOMEN), TherOx, Consumers Union, and the TIMI 37A trial.


   References
Top
 Technical advances
 Myocardial viability
 Cardiac Resynchronization...
 CAD
 LV Function
 Molecular imaging
 Conclusions
 References
 

  1. Hatada K, Riou LM, Ruiz M, et al. 99mTc-N-DBODC5, a new myocardial perfusion imaging agent with rapid liver clearancecomparison with 99mTc-sestamibi and 99mTc-Tetrofosmin in rats. J Nucl Med 2004;45:2095-2101.[Abstract/Free Full Text]
  2. Abidov A, Bax JJ, Hayes SW, et al. Integration of automatically measured transient ischemic dilation ratio into interpretation of adenosine stress myocardial perfusion SPECT for detection of severe and extensive CAD J Nucl Med 2004;45:1999-2007.[Abstract/Free Full Text]
  3. Dupuis J, Arsenault A, Meloche B, Harel F, Staniloae C, Gregoire J. Quantitative hyperemic reactivity in opposed limbs during myocardial perfusion imaginga new marker of CAD. J Am Coll Cardiol 2004;44:1473-1477.[Abstract/Free Full Text]
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