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Approaches for Assessing Myocardial Viability With Multidetector-Row CT
Y ASUSHI K OYAMA , MD AND T ERUHITO M OCHIZUKI , MD
INTRODUCTION
Because the myocardial reperfusion status is pivotal to the prognosis of patients who have suffered an acute myocardial infarction (AMI), the assessment of microvascular flow after reperfusion therapy is of great importance.
Gibson et al. (1) have recently reported that patients with both normal epicardial flow (thrombolysis in myocardial infarction [TIMI—see Note 1] grade 3 flow) and normal tissue- level perfusion (TIMI myocardial perfusion [see Note 2] grade 3) are at an extremely low risk for mortality.
Conventionally, myocardial perfusion has been evaluated mainly using nuclear imaging techniques (2,3). Contrast- enhanced dynamic magnetic resonance imaging (MRI) (4–6) and myocardial contrast echocardiography (7–10) are newcom- ers that can assess myocardial perfusion. Electron beam com- puted tomography (EBCT) also provides reliable information on myocardial perfusion (11–13).
In this chapter, we describe the meaning of X-ray CT enhancement and the classification of enhancement patterns as clinical predictors in patients with AMI after successful percu- taneous coronary interventions (PCI).
ENHANCEMENT IN ACUTE MYOCARDIAL INFARCTION (EARLY DEFECT, LATE ENHANCEMENT, RESIDUAL DEFECT)
Early defect (ED) is observed as a myocardial perfusion defect (dark zone) in the early image (30–60 s). Residual defect (RD) is observed as smaller dark regions observed in the subendocardium, surrounded by a partially hyperenhanced zone of late enhancement (LE) in the late image (5–10 min) (Fig. 1).
The density of the ED (30.2 ± 11 Hounsfield units [HU]) was significantly lower than that of normal myocardium (102.1 ± 9.0 HU, p < 0.0001). The LE (112.9 ± 18.5 HU) presented with higher density than RD (59.3 ± 11 HU) (p < 0.0001).
ED IN RELATION TO WALL THICKNESS AND WALL MOTION IN CHRONIC PHASE (1 MO) (14)
In AMI patients after successful PCI, the depth (subendocar- dial or transmural) of the ED can predict wall thickness and wall motion in the chronic phase (1 mo).
The protocol for the contrast-enhanced CT was as follows:
One hundred mL of an iodine contrast medium was intrave- nously injected at a rate of 1.5 mL/s, with the early image being taken 45 s after the start of the injection.
Left ventriculography (LVG) was performed immediately after the acute-phase intervention and again at the chronic phase (1 mo) to evaluate regional wall motion. The wall motion was scored into six grades (5: normal; 4: mild hypokinesia; 3: mod- erate hypokinesia; 2: severe hypokinesia; 1: akinesia; 0: dyski- nesia) and used as the regional wall motion score (RWM). The corresponding LVG segment to the CT site is shown in Fig. 2.
Myocardial enhancement patterns were classified into three groups: Group N (normal), showing no ED, was consid- ered as the normal group; Group SE (region retained in the subendocardium), the region in which ED accounted for less than 50%; and Group TM (region existing transmurally), the region in which ED accounted for more than 50%. Addi- tionally, the mean myocardial wall thickness of the seven regions was calculated and compared in both acute and 1-mo phases.
ED VS WALL THICKNESS
A case of Group SE is shown in Fig. 3A, and a case in the TM group is shown in Fig. 3B.
As shown in Fig. 4A, wall thickness in Group N showed no significant difference between the acute and chronic phases.
In Group SE, the wall thickness decreased slightly in the chronic phase (p < 0.05). In Group TM, the wall thickness significantly decreased in the chronic phase (p < 0.001), whose rate of decrease was larger than that of the SE group. As the depth of the ED increased, wall thickness in the chronic phase decreased.
ED VS WALL MOTION (RWM SCORE)
The RWM in Group N exhibited no difference between the acute and the chronic phases. In Group SE, the RWM improved in the chronic phase, and in Group TM, the RWM did not improve (Fig. 4B). The RWM in Group SE improved, while in Group TM it remained worse.
Thus ED by contrast-enhanced CT is useful as a predictor of wall thickness and regional wall motion at 1 mo after successful reperfusion therapy in AMI.
20
From: Contemporary Cardiology: CT of the Heart:
Principles and Applications
Edited by: U. Joseph Schoepf © Humana Press, Inc., Totowa, NJ
Fig. 1. Early defect in the early phase (left), and residual defect and delayed enhancement in the delayed phase (right).
Fig. 2. Corresponding segments of CT (A) and left ventriculography (B).
ED VS TL-201 MYOCARDIAL PERFUSION SINGLE PHOTON EMISSION CT (15,16)
When the early defect from the contrast-enhanced CT was compared with the defects on Tl-201 myocardial perfusion single photon emission CT (SPECT), the location and extent were well concordant, indicating that myocardial perfusion can be evaluated with CT. Figure 5 shows an infero-lateral trans-
mural AMI after primary PCI. Figure 6 shows an antero-septal transmural AMI after primary PCI. Location and extent of the perfusion defects were well concordant.
TWO-PHASE CONTRAST-ENHANCED CT (17)
METHOD OF TWO-PHASE CONTRAST-ENHANCED CTInformation regarding myocardial perfusion in the late phase
(5–10 min), along with information in the early phase, seems to
CHAPTER 20 / ASSESSING MYOCARDIAL VIABILITY WITH MDCT 209
209
Fig. 3. (A) A case of Group-SE. The early defect (ED) was observed in the endocardium of the inferior wall by the contrast-enhanced helical CT in the acute phase. At the site, there was no decrease in the wall thickness at 1 mo. (B) A case of Group-TM. By the contrast-enhanced CT in the acute phase, ED was observed in the whole layer of the antero-septal wall. At the site, the wall thickness decreased at 1 mo. As shown by the arrow, there was no improvement of wall motion in the left ventriculography.
Fig. 4. (A) Wall motion (regional wall motion score, RWM) in the chronic phase (1 mo) in Group-N, Group-SE, and Group-TM). RWM in group-SE improved, while in Group-TM it became worse. (B) Wall thickness in the chronic phase (1 mo) in Group-N, Group-SE, and Group- TM). As the depth of early defect increased, wall thickness decreased in the chronic phase.
Fig. 5. A case of infero-lateral transmural acute myocardial infarction after successful primary percutaneous coronary intervention. Location and extent of the perfusion defects were well concordant. The hypoenhanced (dark) region between arrows indicates the perfusion defect by contrast-enhanced CT. Note that the perfusion defect by CT is similar in extent and location to the perfusion defect on Tl-201 myocardial perfusion single photon emission CT. Tx = transaxial image; Sx = short axis; and Be = Bull’s eye map.
CHAPTER 20 / ASSESSING MYOCARDIAL VIABILITY WITH MDCT 211
yield a more detailed prediction of functional recovery in the chronic phase.
The protocol for the contrast-enhanced CT was as follows.
A nonion iodine contrast medium (300 mg iodine/mL) was intravenously administrated at a rate of 1.5 mL/s for the first (early) scan, with the early image being taken 45 s after the start of the administration. Then the same contrast medium was
infused at a rate of 0.1 mL/s for the second scan to acquire the late image, which was taken 7 min after the start of the admin- istration. A total of 150 mL of the contrast medium was used.
CLASSIFICATION OF ENHANCEMENT PATTERNS
Enhancement patterns can be classified into three groups (Fig. 7): Group 1, the absence of ED in the early phase, and the presence of LE without RD in the late phase; Group 2, the
Fig. 6. A case of antero-septal transmural acute myocardial infarction after successful primary percutaneous coronary intervention. Location and extent of the perfusion defects were well concordant. The hypoenhanced (dark) region between arrows indicates the perfusion defect by contrast-enhanced CT. Note that the perfusion defect by CT is similar in extent and location to the perfusion defect on Tl-201 myocardial perfusion single photon emission CT. Tx, transaxial image; Sx, short axis; and Be, Bull’s eye map.Fig. 7. Three enhancement patterns. Illustration (A) and typical cases (B). Group 1: the absence of early defect (ED) in the early phase, and the presence of late enhancement (LE) without residual defect (RD) in the late phase. Group 2: the presence of ED in the early phase, and the presence of LE without RD in the late phase. Group 3: the presence of ED in the early phase, and the presence of both LE and RD.
presence of ED in the early phase, and the presence of LE without RD in the late phase; and Group 3, the presence of ED in the early phase, and the presence of both LE and RD in the late phase. Figure 7B shows typical cases of the enhancement patterns.
ENHANCEMENT PATTERNS ON TWO-PHASE CONTRAST-ENHANCED CT VS LEFT-VENTRICULAR FUNCTION AND VOLUME IN THE CHRONIC PHASE (17)
Thirty AMI patients, after successful PCI (4.3 ± 1.2 h after onset), underwent a two-phase contrast-enhanced CT (37 ± 4 h after direct angioplasty). Conventional LVG was performed immediately after the PCI as the acute study. They had both coronary angiography (CAG) and LVG as the chronic study (28 ± 3 d).
COMPARISON OF LEFT-VENTRICULAR VOLUME
AND FUNCTION IN EACH GROUP BY CONVENTIONAL LVG
The left-ventricular volume and functional parameters (end- diastolic volume [EDV], end-systolic volume [ESV], and ejec- tion fraction [EF]) in each group are summarized in Fig. 8.
In Group 1, the left-ventricular ejection fraction (LV-EF) improved. In Group 2, the LVEF was not significantly differ- ent. In Group 3, the EDV increased and the LV-EF decreased.
The lack of evidence of the ED, as seen in Group 1, indicates a functional improvement in the chronic phase. Residual defect, as seen in Group 3, indicates the worst functional outcome, i.e., deterioration in the chronic phase. Diminishment of the ED, as seen in Group 2, exhibited an intermediate functional recovery
between Group 1 and Group 3. Thus, two-phase contrast- enhanced CT predicts left-ventricular functional recovery in patients with AMI after successful reperfusion therapy.
ENHANCEMENT PATTERNS ON TWO-PHASE
CONTRAST-ENHANCED CT VS 201TL/99MTC-PYROPHOSPHATE DUAL-ISOTOPE SPECT
Patients with RD > LE zones showed a perfusion defect of
201
Tl and strong uptake of
99mTc-pyrophosphate (see Note 3).
Patients with RD < LE zones showed an overlap of
201Tl and
99m
Tc- pyrophosphate.
A few patients with subendocardial-early defects, having only wide LE without RD, showed normal perfusion without
99mTc- pyrophsphate accumulations. Thus, a large RD compared with LE indicates the least viability. In other words, RD in the late image suggests an abundance of necrotic tissue injured by AMI.
Fig. 9 shows a comparison of two-phase contrast-enhanced CT with
201Tl/
99mTc-pyrophosphate dual isotope SPECT.
THE MEANING OF EACH ENHANCEMENT PATTERN
SIGNIFICANCE OF AN EDThe contrast medium is thought to reach the microvascular bed in the early phase after an intravenous administration. An EBCT study (13) reported that myocardial enhancement in the early phase reflected the volume of the vascular bed.
Recently, reduced signal intensity on first-pass MRI con- trast images has been shown to indicate reduced blood flow
(18). Therefore, the ED observed on CT would also reflect a Fig. 8. Left-ventricular volume (end-diastolic volume [EDV], end-systolic volume [ESV] and functional parameters (left-ventricular ejection fraction) in Group 1 to 3 are summarized. In Group 1, the ejection fraction (EF) significantly improved from 61 ± 14% to 78 ± 10% (p < 0.05).In Group 2, the EF was not significantly different. In Group 3, the EDV significantly increased from 117 ± 38 mL to 147 ± 41 mL and the EF significantly decreased from 63 ± 13% to 51 ± 15%.
CHAPTER 20 / ASSESSING MYOCARDIAL VIABILITY WITH MDCT 213
Fig. 9. Comparison of two-phase contrast-enhanced CT with 201Tl/99mTc-pyrophosphate dual isotope single photon emission CT. Case 1 was a patient with acute myocardial infarction (AMI) after left ascending coronary artery reperfusion (white arrows), such as Group 1 (an almost normal enhancement pattern of CT), who had a normal uptake of 201Tl and an absence of 99mTc-pyrophosphate (99mTc-PYP) accumulations.
Case 3 was a patient with AMI after left ascending coronary artery reperfusion, and Case 4 was a patient with AMI after left ascending coronary artery reperfusion, such as Group 3 (early defect [ED] (+), late enhancement [LE] (+), residual defect [RD] (+)). The ED is similar to the uptake of 201Tl. However, subendo-ED of Case 2, who was a patient with AMI after circumflex coronary artery reperfusion, such as Group 2 (ED [+], LE [+], RD [-]), had a mismatch of uptake of 201Tl and ED. Especially the infracted area of LE in Case 2 had an absence of 99mTc-PYP, on the other hand, the infarct area of LE with small RD of Case 3 had a small accumulation of 99mTc-PYP. That is, LE was not the necrotic area of AMI. RDs in Case 3 and Case 4 appear to be the necrotic areas, because these RD areas correlated well with the accumulation of 99mTc-PYP.
These findings are important in evaluating the myocardial viability of using CT.
decrease in the volume of the vascular bed, i.e., a decrease of the myocardial blood flow.
Using an experimental infarct-reperfusion model in dogs, Braunwald et al. (19) classified the condition of myocardial tissue into four layers from the endocardial side. The first layer corresponded to a viable and very thin myocardium, receiving oxygen directly from the left ventricle; the second layer to myocardial necrosis with extensive capillary (microcirculation) disorder; the third layer to myocardial necrosis, in which blood supply was preserved to some extent; and the fourth layer to stunned myocardium that had escaped from necrosis.
The ED in our study may correspond to myocardial necro- sis with extensive capillary (microcirculation) disorder, or to myocardial necrosis in which blood supply was preserved to
some extent—that is, tissue showed mild to severe micro- vascular damage and myocardial necrosis, owing to the wall thickness in Group 2 and Group 3, showing that the ED was significantly reduced.
SIGNIFICANCE OF RD AND LE
After the contrast medium reaches the microvascular bed, it gradually flows into the interstitium (extracellular space), remains for some time, and then washed out slowly. Therefore, myocardial enhancement in the late phase mainly reflects the characteristics of the interstitium—that is, the volume of the interstitial space (12,13).
When the RD was detected, as in Group 3, functional recov-
ery was not observed. However, when ED turned into LE, as in
Group 2, deterioration of left-ventricular function was mini-
mal, or less than that observed in Group 3. We speculate that the area of the RD might correspond to myocardial necrosis with extensive capillary disorder—i.e., microvascular no-reflow—
and that LE might correspond to the layer where blood supply was preserved to some degree, indicating the possibility of residual myocardial viability, although microvascular flow was disturbed by edema within 48 h after PCI.
Considering the findings of SPECT studies and our results, we conclude that the RD indicated a necrotic area as a result of severe microvascular obstruction “microvascular no-reflow”
by red blood cells and necrotic debris (20), as seen in the “wave front” phenomenon of ischemic necrosis (21,22). Since the presence of
99mTc-pyrophosphate in Group 3 was well corre- lated with RD, the myocardial enhancement pattern in Group 3 indicates less antegrade microvascular flow beyond the point of microvascular obstruction than seen in Group-2. As a result of the incomplete perfusion in the microvascular level, the necrotic area of Group 3 increased among three groups.
Basically, the pharmacokinetic properties of X-ray con- trast agents are similar to those of the well-known gadolinium complexes (23–25) for MRI. Judd et al. reported that the hyperintense regions observed on delayed MRI images were generally smaller than the risk region and larger than regions of necrosis as defined by triphenyltetrazolium chloride stain- ing (26). This would indicate that at least part of the delayed hyperintense region was viable myocardium. Yokota et al.
investigated Gd-enhanced MRI images 5 to 10 min after an intravenous gadopentate dimeglumine (Gd-DTPA) injection in patients with nonreperfused myocardial infarction (27).
They qualitatively analyzed Gd-enhanced MRI findings in relation to peak creatine phosphokinase levels, wall motion, and coronary angiography, and concluded that subendo- cardial or transmural hyper-enhancement could reflect the existence of viable myocardium, while subendocardial hypo- enhancement was associated with necrotic myocardium.
In general, there is a consensus that delayed hyper-enhance- ment on MRI reflects nonviable myocardium (28). But in our study, the LE presented both in Group 1 and in Group 2, indi- cating that the LE included viable myocardium, at least in con- trast-enhanced CT studies within 48 h after reperfusion therapy, as seen in our results in this chapter.
The myocardium and the microvasculature changes dynami- cally during the healing stage in the acute phase after successful reperfusion; therefore, timing of the CT study after reperfusion therapy is important in order to assess the myocardial enhance- ment pattern with contrast-enhanced CT.
RELATIONSHIP BETWEEN ED, RD, AND THE NO-REFLOW PHENOMENON
The causes of the no-reflow phenomenon include experi- mental obstruction of the lumen of vascular vessels by neutro- phils or platelets, compression towing to edema of myocardial cells out of the vascular vessels, and a change in the viscosity of blood (29).
In our study, the ED and RD existed even after successful reperfusion at the epicardial coronary artery level and improve- ment of coronary blood flow, indicating that the circulation disorder at the level of coronary microcirculation level, that is, the no-reflow at the regional microcirculation level, still per-
sisted after successful reperfusion. Additionally, in patients showing RD in our study, this no-reflow phenomenon exists, regardless of its various degrees and causes, in the coronary microcirculation system after successful reperfusion in coro- nary arteriography. We believe that the no-reflow at the level of regional microcirculation is involved in decreases in cardiac function and wall motion in the chronic phase.
We conclude that contrast-enhanced CT is useful in evalu- ating myocardial enhancement, which may serve as a predictor of changes in wall motion and thickness, left-ventricular func- tion, and myocardial viability after PCI in patients with AMI.
PITFALLS OF ENHANCEMENT PATTERNS In the assessment of perfusion, there are some pitfalls.
In patients with old myocardial infarction, or re-AMI, we may also detect lipid degeneration in the left-ventricular myo- cardium (Fig. 10A). This is always clearly detectable in plain images without the administration of a contrast medium. This should not be interpreted as ED or RD on two-phase contrast- enhanced CT. In patients with old myocardial infarction, or re-AMI, we may detect a thrombus in the left ventriculum (Fig. 10B), which is always clearly detectable in both early and late images. This should not be misinterpreted as ED or RD. In patients with old myocardial infarction or re-AMI, we may even detect calcium in the left-ventricular myocardium (Fig.
10C). This is clearly detectable in plain CT, and should not be misinterpreted as LE on two-phase contrast-enhanced CT.
STUDY LIMITATIONS AND FUTURE OF MDCT
ADVANTAGES OF CARDIAC CT FOR PATIENTS WITH AMIThe advantages of cardiac CT are generally as follows: (1) no blind area; (2) shorter acquisition time (less than 30 s); (3) metal devices such as an infusion pump, pacemaker, and intra-aortic balloon pump (IABP) are acceptable, whereas they are com- monly contraindicated for MRI, and therefore the CT is able to utilize them for the acute phase of AMI; (4) coronary arteries can be evaluated with the same data.
DISADVANTAGES OF CT FOR PATIENTS WITH AMI
The disadvantages of CT over other noninvasive modalities are the use of an iodine contrast medium (however, there were neither major nor minor complications in this study) and X-ray exposure of the two-phase contrast CT. Although the two-phase study requires double dose compared to the single-phase study, overlapping reconstruction does not increase the radiation dose—i.e., it is exactly the same as nonoverlapping reconstruc- tion. The exposed range for cardiac CT (12 cm) is smaller than that of whole-lung or abdominal CT scans. Therefore, the radiation dose is not a limitation.
CLINICAL IMPLICATIONS OF CARDIAC CT
Although cardiac CT is a retrospective analysis, and not a real-time analysisas is echocardiography, it provides a lot of information from data obtained during a 30-s breath-hold acquisition (30–35). The assessment of the myocardial enhance-ment patterns was one of clinical implications of car- diac CT.
NOTES
1. TIMI grade: grade 0 perfusion is no antegrade flow beyond the point of occlusion; grade 1 is minimal incomplete per-
CHAPTER 20 / ASSESSING MYOCARDIAL VIABILITY WITH MDCT 215
fusion of the contrast medium around the clot; grade 2 (partial perfusion) is complete but delayed perfusion of the distal coronary bed with contrast material; and grade 3 (complete perfusion) is antegrade flow to the entire distal bed at a normal rate.
2. TIMI myocardial perfusion grade (TMPG): in TMPG 0, there is minimal or no myocardial blush; in TMPG 1, dye stains the myocardium and this stain persists until the next injection; in TMPG 2, dye enters the myocardium but washes out slowly so that the dye is strongly persistent at the end of the injection; and in TMPG 3, there is normal entrance and exit of dye in the myocardium so that dye is mildly persistent at the end of the injection.
3. 99mTc-pyrophosphate localizes to denatured proteins within the mitochondria in areas of myocardial necrosis, highlighting AMI region during the 7 to 10 d after the onset.
ACKNOWLEDGMENTS
We are grateful to Taketoshi Ito, MD, Hiroshi Matsuoka, MD, Hiroshi Higashino, MD, Hideo Kawakami., MD, Jun Aono, MD, Kana Sakamoto, MD, and Junko Kato, MD, in the Department of Cardiology and Radiology, Imabari Hospital; Kazuhisa Nishimura, MD, Hideki Okayama, MD, Takumi Sumimoto, MD,
in the Kitaishikai Hospital; and Shigru Nakata, RT, Katsuji Inoue, MD, Tsuyoshi Matsunaka, MD, and Jitsuo Higaki, MD, the Chairman of the 2nd Department of Internal Medicine in Ehime University School of Medicine, for their excellent assistance in publication. We are very grateful to Masaya Doi, RT, Masato Imai, RT, Yasuyuki Takahashi, RT, Hideyuki Chiba, RT, Takashi Okamoto, RT, Isao Ouchi, RT, and Hiroshi Miguchi, RT, for their excellent technical assistance.
REFERENCES
1. Gibson CM, Cannon CP, Murphy SA, et al. Relationship of TIMI myocardial perfusion grade to mortality after administration of thrombolytic drugs. Circulation 2000;101:125–130.
2. Abe M, Kazatani Y, Fukuda H, Tatsuno H, Habara H, Shinbata H.
Left ventricular volumes, ejection fraction, and regional wall motion calculated with gated technetium-99m tetrofosmin SPECT in reperfused acute myocardial infarction at super-acute phase: com- parison with left ventriculography. J Nucl Cardiol 2000;7:569–574.
3. Watanabe K, Sekiya M, Ikeda S, Miyagawa M, Kinoshita M, Kumano S. Comparison of adenosine triphosphate and dipyridamole in diagnosis by thallium-201 myocardial scintigraphy. J Nucl Med 1997;38:577–581.
4. Al-Saadi N, Nagel E, Gross M, et al. Noninvasive detection of myocardial ischemia from perfusion reserve based on cardiovascu- lar magnetic resonance. Circulation 2000;101:1379–1383.
Fig. 10. Pitfalls of enhancement patterns. Fatty degeneration in old myocardial infarction (A). Left-ventricular thrombus (B). Left-ventricular calcium deposit (C).
5. Rogers WJ Jr, Kramer CM, Geskin G, et al. Early contrast-enhanced MRI predicts late functional recovery after reperfused myocardial infarction. Circulation 1999;99:744–750.
6. Pislaru SV, Ni Y, Pislaru C, et al. Noninvasive measurements of infarct size after thrombolysis with a necrosis-avid MRI contrast agent. Circulation 1999;99:690–696.
7. Bogaert J, Maes A, Van de Werf F, et al. Functional recovery of subepicardial myocardial tissue in transmural myocardial infarction after successful reperfusion: an important contribution to the improvement of regional and global left ventricular function. Circu- lation 1999;99:36–43.
8. Ito H, Tomooka T, Sakai N, et al. Lack of myocardial perfusion immediately after successful thrombolysis. A predictor of poor recovery of left ventricular function in anterior myocardial infarc- tion. Circulation 1992;85:1699–1705.
9. Scherrer-Crosbie M, Liel-Cohen N, Otsuji Y, et al. Myocardial per- fusion and wall motion in infarction border zone: assessment by myocardial contrast echocardiography. J Am Soc Echocardiogr 2000;13:353–357.
10. Lepper W, Hoffmann R, Kamp O, et al. Assessment of myocardial reperfusion by intravenous myocardial contrast echocardiography and coronary flow reserve after primary percutaneous transluminal coronary angioplasty [correction of angiography] in patients with acute myocardial infarction. Circulation 2000;101:2368–2374.
11. Hamada S, Naito H, Takamiya M. Evaluation of myocardium in ischemic heart disease by ultrafast computed tomography. Jpn Circ J 1992;56:627–631.
12. Naito H, Saito H, Takamiya M, et al. Quantitative assessment of myocardial enhancement with iodinated contrast medium in patients with ischemic heart disease by using ultrafast x-ray computed tomography. Invest Radiol 1992;27:436–442.
13. Naito H, Saito H, Ohta M, Takamiya M. Significance of ultrafast computed tomography in cardiac imaging: usefulness in assessment of myocardial characteristics and cardiac function. Jpn Circ J 1990;
54:322–327.
14. Koyama Y, Matsuoka H, Higashino H, et al. Wall motion and wall thickness analysis of after receiving successful reperfusion therapy in acute myocardial infarction: an assessment of early perfusion defect by enhanced helical CT. Jpn J Interv Cardiol 2001;16:
233–242.
15. Koyama Y, Matsuoka H, Higasino H, et al. Assessment of Myocar- dial Infarct Volume by Contrast Enhancement CT. The Radiological Society of North America 87th Scientific Assembly and Annual Meeting November 25–30, 2001 Supplement to Radiology 2001;
221(P):196.
16. Koyama Y, Matsuoka H, Higasino H, et al. Assessment of Myocar- dial Infarct Size by Contrast Enhanced CT. American Heart Associa- tion Scientific Sessions 2001, November 11–14, 2001 Supplement to Circulation 2001;104(17):II-477.
17. Koyama Y, Matsuoka H, Higasino H, et al. Early Myocardial Perfu- sion Defect and Late Enhancement on Enhancement CT Predict Clinical Outcome in Patients with Acute Myocardial Infarction after Reperfusion Therapy. The Radiological Society of North America 87th Scientific Assembly and Annual Meeting November 25–30, 2001. Supplement to Radiology 2001;221(P):196.
18. Rochitte CE, Lima JA, Bluemke DA, et al. Magnitude and time course of microvascular obstruction and tissue injury after acute myocardial infarction. Circulation 1998;98:1006–1014.
19. Braunwald E, Kloner RA. Myocardial reperfusion: a double-edged sword? J Clin Invest 1985;76:1713–1719.
20. Engler RL, Schmid-Schonbein GW, Pavelec RS. Leukocyte capil- lary plugging in myocardial ischemia and reperfusion in the dog.
Am J Pathol 1983;111:98–111.
21. Reimer KA, Lowe JE, Rasmussen MM, Jennings RB. The wavefront phenomenon of ischemic cell death. 1. Myocardial infarct size vs duration of coronary occlusion in dogs. Circulation 1977;56:786–794.
22. Reimer KA, Jennings RB. The “wavefront phenomenon” of myo- cardial ischemic cell death. II. Transmural progression of necrosis within the framework of ischemic bed size (myocardium at risk) and collateral flow. Lab Invest 1979;40:633–644.
23. Mutzel W, Speck U, Weinmann HJ. Pharmacokinetics of iopromide in rat and dog. Fortschr Geb Rontgenstrahlen Nuklearmed Erganzungsbd 1983;118:85–90.
24. Allard M, Doucet D, Kien P, Bonnemain B, Caille JM. Experimental study of DOTA-gadolinium. Pharmacokinetics and pharmacologic properties. Invest Radiol 1988;23 Suppl 1:S271–274.
25. Tauber U, Mutzel W, Schulze PE. Whole body autoradiographic distribution studies on nonionic x-ray contrast agents in pregnant rats. Fortschr Geb Rontgenstrahlen Nuklearmed Erganzungsbd 1989;128:215–219
26. Judd RM, Lugo-Olivieri CH, Arai M, et al. Physiological basis of myocardial contrast enhancement in fast magnetic resonance images of 2-day-old reperfused canine infarcts. Circulation 1995;92:
1902–1910.
27. Yokota C, Nonogi H, Miyazaki S, et al. Gadolinium-enhanced mag- netic resonance imaging in acute myocardial infarction. Am J Cardiol 1995;75:577–581.
28. Wu K, Zerhouni E, Judd R, et al. Prognostic significance of microvascular obstruction by magnetic resonance imaging in patients with acute myocardial infarction. Circulation 1998;97:765–772.
29. Engler RL, Schmid-Schönbein GW, Pavelec RS. Leukocyte capil- lary plugging in myocardial ischemia and reperfusion in the dog.
Am J Pathol 1983;111:98–111.
30. Becker CR, Ohnesorge BM, Schoepf UJ, Reiser MF. Current devel- opment of cardiac imaging with multidetector-row CT. Eur J Radiol 2000;36:97–103.
31. Mochizuki T, Murase K, Higashino H, et al. Two- and three-dimen- sional CT ventriculography: a new application of helical CT. AJR 2000;174:203–208.
32. Mochizuki T, Murase K, Koyama Y, Higashino H, Ikezoe J. LAD stenosis detected by subsecond spiral CT. Circulation 1999;99:1523.
33. Mochizuki T, Koyama Y, Tanaka H, Ikezoe J, Shen Y, Azemoto S.
Left ventricular thrombus detected by two- and three-dimensional computed tomographic ventriculography: a new application of helical CT. Circulation 1998;98:933–934.
34. Koyama Y, Matsuoka H, Higasino H, et al. Four-dimensional cardiac image by helical computed tomography. Circulation 1999;100:e61–e62.
35. Koyama Y, Matsuoka H, Higashino H, et al. Left ventricular hyper- trophy demonstrated by four-dimensional myocardiography by helical computed tomography. Circulation 2001;103:e15–e17.
