Li-Yueh Hsu

Retrospective Determination of the Area at Risk for Reperfused Acute Myocardial Infarction With T2-Weighted Cardiac Magnetic Resonance Imaging Histopathological and Displacement Encoding With Stimulated Echoes (DENSE) Functional Validations

Background— The aim of this study was to determine whether edema imaging by T2-weighted cardiac magnetic resonance (CMR) imaging could retrospectively delineate the area at risk in reperfused myocardial infarction. We hypothesized that the size of the area at risk during a transient occlusion would be similar to the T2-weighted hyperintense region observed 2 days later, that the T2-weighted hyperintense myocardium would show partial functional recovery after 2 months, and that the T2 abnormality would resolve over 2 months. Methods and Results— Seventeen dogs underwent a 90-minute coronary artery occlusion, followed by reperfusion. The area at risk, as measured with microspheres (9 animals), was comparable to the size of the hyperintense zone on T2-weighted images 2 days later (43.4±3.3% versus 43.0±3.4% of the left ventricle; P=NS), and the 2 measures correlated (R=0.84). The infarcted zone was significantly smaller (23.1±3.7; both P<0.001). To test whether the hyperintense myocardium would exhibit partial functional recovery over time, 8 animals were imaged on day 2 and 2 months later. Systolic strain was mapped with displacement encoding with stimulated echoes. Edema, as detected by a hyperintense zone on T2-weighted images, resolved, and regional radial systolic strain partially improved from 4.9±0.7 to 13.1±1.5 (P=0.001) over 2 months. Conclusions— These findings are consistent with the premise that the T2 abnormality depicts the area at risk, a zone of reversibly and irreversibly injured myocardium associated with reperfused subendocardial infarctions. The persistence of postischemic edema allows T2-weighted CMR to delineate the area at risk 2 days after reperfused myocardial infarction.

Myocardial Edema as Detected by Pre-Contrast T1 and T2 CMR Delineates Area at Risk Associated With Acute Myocardial Infarction

OBJECTIVES The aim of this study was to determine whether cardiac magnetic resonance (CMR) in vivo T1 mapping can measure myocardial area at risk (AAR) compared with microspheres or T2 mapping CMR. BACKGROUND If T2-weighted CMR is abnormal in the AAR due to edema related to myocardial ischemia, then T1-weighted CMR should also be able to detect and accurately quantify AAR. METHODS Dogs (n = 9) underwent a 2-h coronary occlusion followed by 4 h of reperfusion. CMR of the left ventricle was performed for mapping of T1 and T2 prior to any contrast administration. AAR was defined as regions that had a T1 or T2 value (ms) >2 SD from remote myocardium, and regions with microsphere blood flow (ml/min/g) during occlusion <2 SD from remote myocardium. Infarct size was determined by triphenyltetrazolium chloride staining. RESULTS The relaxation parameters T1 and T2 were increased in the AAR compared with remote myocardium (mean ± SD: T1, 1,133 ± 55 ms vs. 915 ± 33 ms; T2, 71 ± 6 ms vs. 49 ± 3 ms). On a slice-by-slice basis (n = 78 slices), AAR by T1 and T2 mapping correlated (R(2) = 0.95, p < 0.001) with good agreement (mean ± 2 SD: 0.4 ± 16.6% of slice). On a whole-heart analysis, T1 measurements of left ventricular mass, AAR, and myocardial salvage correlated to microsphere measures (R(2) = 0.94) with good agreement (mean ± 2 SD: -1.4 ± 11.2 g of myocardium). Corresponding T2 measurements of left ventricular mass, AAR, and salvage correlated to microsphere analysis (R(2) = 0.96; mean ± 2 SD: agreement 1.6 ± 9.2 g of myocardium). This yielded a median infarct size of 30% of the AAR (range 12% to 52% of AAR). CONCLUSIONS For determining AAR after acute myocardial infarction, noncontrast T1 mapping and T2 mapping sequences yield similar quantitative results, and both agree well with microspheres. The relaxation properties T1 and T2 both change in a way that is consistent with the presence of myocardial edema following myocardial ischemia/reperfusion.

Nitrite Anion Provides Potent Cytoprotective and Antiapoptotic Effects as Adjunctive Therapy to Reperfusion for Acute Myocardial Infarction

Background— Accumulating evidence suggests that the ubiquitous anion nitrite (NO2−) is a physiological signaling molecule, with roles in intravascular endocrine nitric oxide transport, hypoxic vasodilation, signaling, and cytoprotection. Thus, nitrite could enhance the efficacy of reperfusion therapy for acute myocardial infarction. The specific aims of this study were (1) to assess the efficacy of nitrite in reducing necrosis and apoptosis in canine myocardial infarction and (2) to determine the relative role of nitrite versus chemical intermediates, such as S-nitrosothiols. Methods and Results— We evaluated infarct size, microvascular perfusion, and left ventricular function by histopathology, microspheres, and magnetic resonance imaging in 27 canines subjected to 120 minutes of coronary artery occlusion. This was a blinded, prospective study comparing a saline control group (n=9) with intravenous nitrite during the last 60 minutes of ischemia (n=9) and during the last 5 minutes of ischemia (n=9). In saline-treated control animals, 70±10% of the area at risk was infarcted compared with 23±5% in animals treated with a 60-minute nitrite infusion. Remarkably, a nitrite infusion in the last 5 minutes of ischemia also limited the extent of infarction (36±8% of area at risk). Nitrite improved microvascular perfusion, reduced apoptosis, and improved contractile function. S-Nitrosothiol and iron-nitrosyl-protein adducts did not accumulate in the 5-minute nitrite infusion, suggesting that nitrite is the bioactive intravascular nitric oxide species accounting for cardioprotection. Conclusions— Nitrite has significant potential as adjunctive therapy to enhance the efficacy of reperfusion therapy for acute myocardial infarction.

Quantitative myocardial perfusion analysis with a dual-bolus contrast-enhanced first-pass MRI technique in humans.

To compare fully quantitative and semiquantitative analysis of rest and stress myocardial blood flow (MBF) and myocardial perfusion reserve (MPR) using a dual‐bolus first‐pass perfusion MRI method in humans.

Magnetic resonance imaging delineates the ischemic area at risk and myocardial salvage in patients with acute myocardial infarction.

Background—The area at risk (AAR) is a key determinant of myocardial infarction (MI) size. We investigated whether magnetic resonance imaging (MRI) measurement of AAR would be correlated with an angiographic AAR risk score in patients with acute MI. Methods and Results—Bright-blood, T2-prepared, steady-state, free-precession MRI was used to depict the AAR in 50 consecutive acute MI patients, whereas infarct size was measured on gadolinium late-contrast-enhancement images. AAR was also estimated by the APPROACH and DUKE angiographic jeopardy scores and ST-segment elevation score. Myocardial salvage was calculated as AAR minus infarct size. Results are mean±SD unless specified otherwise. Patients were 61±12 years of age, 76% had an ST-segment elevation MI, and 20% had a prior MI. All underwent MRI 4±2 days after initial presentation. The relation between MRI and the APPROACH angiographic estimates of AAR was similar (overall size relative to left ventricular mass was 32±12% vs 30±12%, respectively, P=0.33), correlated well (r=0.78, P<0.0001), and had a 2.5% bias on Bland-Altman analysis. The DUKE jeopardy score underestimated AAR relative to infarct size and was correlated less well with MRI (r=0.39, P=0.0055). ST-segment elevation score underestimated infarct size in 19 subjects (50%) and was not correlated with MRI (r=0.27, P=0.06). Myocardial salvage varied according to Thrombolysis in Myocardial Infarction flow grade at the end of angiography/percutaneous coronary intervention (P=0.04), and Thrombolysis in Myocardial Infarction flow grade was a univariable predictor of myocardial salvage (P=0.011). In multivariable analyses, infarct size was predicted by T2-prepared, steady-state, free-precession MRI (P<0.0001). Conclusions—T2-prepared, steady-state, free-precession MRI delineates the AAR and enables estimation of myocardial salvage when coupled with a measurement of infarct size.

In vivo T2-weighted magnetic resonance imaging can accurately determine the ischemic area at risk for 2-day-old nonreperfused myocardial infarction.

Objectives:To determine whether in vivo T2-weighted cardiac magnetic resonance imaging (MRI) delineates the area at risk (AAR) in 2-day-old nonreperfused myocardial infarction (MI). AAR was defined as the size of the perfusion defect on day 0. MI and the residual ischemic viable border zone comprise the AAR. Materials and Methods:Fourteen dogs with permanent coronary artery occlusion were imaged on day 0 and day 2. The size of the AAR as measured by first-pass magnetic resonance perfusion on day 0 was compared with retrospectively determined AAR using day 2 T2-weighted MRI. Triphenyltetrazolium chloride staining was used to measure infarct size. Microspheres were used to detect residual perfusion. Results:Hyperintense zones on day 2 T2-weighted magnetic resonance images accurately depicted the AAR as measured by first-pass perfusion on day 0 (38.9 ± 3.0 vs. 36.3% ± 3.3% of left ventricular, P = 0.07). Good correlation (R = 0.91) and Bland-Altman agreement was observed between the AAR measurements and the corresponding T2-weighted hyperintense regions. Both measures of AAR were larger than the infarcted zone (25.6% ± 2.5% of left ventricular area; P < 0.001). Conclusions:Hyperintense regions visualized with in vivo T2-weighted cardiac MRI allow determination of the AAR 2 days postinfarction in nonreperfused MI.

Motion-Corrected Free-Breathing Delayed Enhancement Imaging of Myocardial Infarction

Following administration of Gd‐DTPA, infarcted myocardium exhibits delayed enhancement and can be imaged using an inversion‐recovery sequence. A conventional segmented acquisition requires a number of breath‐holds to image the heart. Single‐shot phase‐sensitive inversion‐recovery (PSIR) true‐FISP may be combined with parallel imaging using SENSE to achieve high spatial resolution. SNR may be improved by averaging multiple motion‐corrected images acquired during free breathing. PSIR techniques have demonstrated a number of benefits including consistent contrast and appearance over a relatively wide range of inversion recovery times (TI), improved contrast‐to‐noise ratio, and consistent size of the enhanced region. Comparison between images acquired using segmented breath‐held turbo‐FLASH and averaged, motion‐corrected, free‐breathing true‐FISP show excellent agreement of measured CNR and infarct size. In this study, motion correction was implemented using image registration postprocessing rather than navigator correction of individual frames. Navigator techniques may be incorporated as well. Magn Reson Med 53:194–200, 2005. Published 2004 Wiley‐Liss, Inc.

A quantitative pixel-wise measurement of myocardial blood flow by contrast-enhanced first-pass CMR perfusion imaging: microsphere validation in dogs and feasibility study in humans.

OBJECTIVES The aim of this study was to evaluate fully quantitative myocardial blood flow (MBF) at a pixel level based on contrast-enhanced first-pass cardiac magnetic resonance (CMR) imaging in dogs and in patients. BACKGROUND Microspheres can quantify MBF in subgram regions of interest, but CMR perfusion imaging may be able to quantify MBF and differentiate blood flow at a much higher resolution. METHODS First-pass CMR perfusion imaging was performed in a dog model with local hyperemia induced by intracoronary adenosine. Fluorescent microspheres were the reference standard for MBF validation. CMR perfusion imaging was also performed on patients with significant coronary artery disease (CAD) by invasive coronary angiography. Myocardial time-signal intensity curves of the images were quantified on a pixel-by-pixel basis using a model-constrained deconvolution analysis. RESULTS Qualitatively, color CMR perfusion pixel maps were comparable to microsphere MBF bulls-eye plots in all animals. Pixel-wise CMR MBF estimates correlated well against subgram (0.49 ± 0.14 g) microsphere measurements (r = 0.87 to 0.90) but showed minor underestimation of MBF. To reduce bias due to misregistration and minimize issues related to repeated measures, 1 hyperemic and 1 remote sector per animal were compared with the microsphere MBF, which improved the correlation (r = 0.97 to 0.98), and the bias was close to zero. Sector-wise and pixel-wise CMR MBF estimates also correlated well (r = 0.97). In patients, color CMR stress perfusion pixel maps showed regional blood flow decreases and transmural perfusion gradients in territories served by stenotic coronary arteries. MBF estimates in endocardial versus epicardial subsectors, and ischemic versus remote sectors, were all significantly different (p < 0.001 and p < 0.01, respectively). CONCLUSIONS Myocardial blood flow can be quantified at the pixel level (∼32 μl of myocardium) on CMR perfusion images, and results compared well with microsphere measurements. High-resolution pixel-wise CMR perfusion maps can quantify transmural perfusion gradients in patients with CAD.

Nonlinear myocardial signal intensity correction improves quantification of contrast-enhanced first-pass MR perfusion in humans

To study the nonlinearity of myocardial signal intensity and gadolinium contrast concentration during first‐pass perfusion MRI, and to compare quantitative perfusion estimates using nonlinear myocardial signal intensity correction.

Bright-blood T(2)-weighted MRI has high diagnostic accuracy for myocardial hemorrhage in myocardial infarction: a preclinical validation study in swine.

Background— Myocardial hemorrhage after myocardial infarction (MI) usually goes undetected. We investigated the diagnostic accuracy of bright-blood T2-weighted cardiac MRI for myocardial hemorrhage in experimental MI. Methods and Results— MI was created in swine by occluding the left anterior descending (n=10) or circumflex (n=5) coronary arteries for 90 minutes followed by reperfusion for ⩽3 days (n=2), 10 days (n=7), or 60 days (n=6). MRI was performed at 1.5 T, using bright-blood T2-prepared steady-state free-precession, T2* and early (1 minute) and late (10–15 minutes) gadolinium enhancement (EGE, LGE, respectively) MRI. Left ventricular sections and histology were assessed for hemorrhage by an experienced cardiac pathologist blinded to the MRI data. Hypointense regions on T2-weighted and contrast-enhanced MRI were independently determined by 3 cardiologists experienced in MRI who were also blinded to the pathology results. Eighty ventricular pathological sections were matched with MRI (n=68 for EGE MRI). All sections with evidence of MI (n=63, 79%) also exhibited hyperintense zones consistent with edema on T2-weighted MRI and infarct on LGE MRI. Myocardial hemorrhage occurred in 49 left ventricular sections (61%) and corresponded with signal voids on 48 T2-weighted (98%) and 26 LGE-MRI (53%). Alternatively, signal voids occurred in the absence of hemorrhage in 3 T2-weighted (90% specificity) and 5 LGE MRI (84% specificity). On EGE MRI, 27 of 43 cases of early microvascular obstruction corresponded with hemorrhage (63% sensitivity), whereas 5 of 25 defects occurred in the absence of hemorrhage (80% specificity). The positive and negative predictive values for pathological evidence of hemorrhage were 94% and 96% for T2-weighted, 84% and 55% for LGE MRI, and 85% and 56% for EGE MRI. Conclusions— Bright-blood T2-weighted MRI has high diagnostic accuracy for myocardial hemorrhage.