Andrew E. Arai

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 T1 mapping and extracellular volume quantification: a Society for Cardiovascular Magnetic Resonance (SCMR) and CMR Working Group of the European Society of Cardiology consensus statement

Rapid innovations in cardiovascular magnetic resonance (CMR) now permit the routine acquisition of quantitative measures of myocardial and blood T1 which are key tissue characteristics. These capabilities introduce a new frontier in cardiology, enabling the practitioner/investigator to quantify biologically important myocardial properties that otherwise can be difficult to ascertain clinically. CMR may be able to track biologically important changes in the myocardium by: a) native T1 that reflects myocardial disease involving the myocyte and interstitium without use of gadolinium based contrast agents (GBCA), or b) the extracellular volume fraction (ECV)–a direct GBCA-based measurement of the size of the extracellular space, reflecting interstitial disease. The latter technique attempts to dichotomize the myocardium into its cellular and interstitial components with estimates expressed as volume fractions. This document provides recommendations for clinical and research T1 and ECV measurement, based on published evidence when available and expert consensus when not. We address site preparation, scan type, scan planning and acquisition, quality control, visualisation and analysis, technical development. We also address controversies in the field. While ECV and native T1 mapping appear destined to affect clinical decision making, they lack multi-centre application and face significant challenges, which demand a community-wide approach among stakeholders. At present, ECV and native T1 mapping appear sufficiently robust for many diseases; yet more research is required before a large-scale application for clinical decision-making can be recommended.

Phase-sensitive inversion recovery for detecting myocardial infarction using gadolinium-delayed hyperenhancement.

After administration of gadolinium, infarcted myocardium exhibits delayed hyperenhancement and can be imaged using an inversion recovery (IR) sequence. The performance of such a method when using magnitude‐reconstructed images is highly sensitive to the inversion recovery time (TI) selected. Using phase‐sensitive reconstruction, it is possible to use a nominal value of TI, eliminate several breath‐holds otherwise needed to find the precise null time for normal myocardium, and achieve a consistent contrast. Phase‐sensitive detection is used to remove the background phase while preserving the sign of the desired magnetization during IR. Experimental results are presented which demonstrate the benefits of both phase‐sensitive IR image reconstruction and surface coil intensity normalization for detecting myocardial infarction (MI). The phase‐sensitive reconstruction method reduces the variation in apparent infarct size that is observed in the magnitude images as TI is changed. Phase‐sensitive detection also has the advantage of decreasing the sensitivity to changes in tissue T1 with increasing delay from contrast agent injection. Magn Reson Med 47:372–383, 2002. Published 2002 Wiley‐Liss, Inc.

Ionizing radiation in cardiac imaging: a science advisory from the American Heart Association Committee on Cardiac Imaging of the Council on Clinical Cardiology and Committee on Cardiovascular Imaging and Intervention of the Council on Cardiovascular Radiology and Intervention.

A preliminary report on medical radiation exposures to the US population based on publicly available sources of data estimated that the collective dose received from medical uses of radiation has increased by >700% between 1980 and 2006.1 Computed tomography (CT) has had an annual growth rate of >10% per year and accounted for ≈50% of the collective dose in 2006. Approximately 65% of the collective CT dose is from studies of chest, abdomen, and pelvis. In 2006, cardiac CT accounted for 1.5% of the collective CT dose; however, utilization of cardiac CT is expected to rise, with the potential to further increase exposure to the population.1 Nuclear medicine studies in the United States have increased by 5% annually to 20 million in 2006 and accounted for ≈25% of the 2006 collective medical radiation dose. Among nuclear medicine studies, cardiac imaging represented 57% of the number of studies and ≈85% of the radiation dose.1 A number of publications on imaging with CT, fluoroscopy, or radioisotopes have emphasized the risks that may be associated with exposure to ionizing radiation.2–4 To make informed decisions concerning the use of medical radiation in imaging procedures, the following are important components: (1) A working knowledge of the principles and uncertainties of the estimation of patient dose and biological risk; (2) a comparison of the risks of radiation exposure with the risks of activities in daily life; and (3) recognition of the potential risk of failing to make important diagnoses or treatment decisions if imaging is not performed because of safety concerns. There is no federal regulation of patient radiation dose, with the exception of mammography. Most federal and state regulations are aimed at equipment performance or the handling of nuclear materials. Therefore, appropriate utilization of the equipment or nuclear material in cardiac …

Cardiovascular Function in Multi-Ethnic Study of Atherosclerosis: Normal Values by Age, Sex, and Ethnicity

OBJECTIVE MRI provides accurate and high-resolution measurements of cardiac anatomy and function. The purpose of this study was to describe the imaging protocol and normal values of left ventricular (LV) function and mass in the Multi-Ethnic Study of Atherosclerosis (MESA). SUBJECTS AND METHODS Eight hundred participants (400 men, 400 women) in four age strata (45-54, 55-64, 65-74, 75-84 years) were chosen at random. Participants with the following known cardiovascular risk factors were excluded: current smoker, systolic blood pressure > 140 mm Hg, diastolic blood pressure > 90 mm Hg, fasting glucose > 110 mg/dL, total cholesterol > 240 mg/dL, and high-density lipoprotein (HDL) cholesterol < 40 mg/dL. Cardiac MR images were analyzed using MASS software (version 4.2). Mean values, SDs, and correlation coefficients in relationship to patient age were calculated. RESULTS There were significant differences in LV volumes and mass between men and women. LV volumes were inversely associated with age (p < 0.05) for both sexes except for the LV end-systolic volume index. For men, LV mass was inversely associated with age (slope = -0.72 g/year, p = 0.0021), but LV mass index was not associated with age (slope = -0.179 g/m2/year, p = 0.075). For women, LV mass (slope = -0.15 g/year, p = 0.30) and LV mass index (slope = 0.0044 g/m2/year, p = 0.95) were not associated with age. LV mass was the largest in the African-American group (men, 181.6 +/- 35.8 [SD] g; women, 128.8 +/- 28.1 g) and was smallest in the Asian-American group (men, 129.1 +/- 20.0 g; women, 89.4 +/- 13.3 g). CONCLUSION The normal LV differs in volume and mass between sexes and among certain ethnic groups. When indexed by body surface area, LV mass was independent of age for both sexes. Studies that assess cardiovascular risk factors in relationship to cardiac function and structure need to account for these normal variations in the population.

Stem Cells for Myocardial Regeneration

Stem cells are being investigated for their potential use in regenerative medicine. A series of remarkable studies suggested that adult stem cells undergo novel patterns of development by a process referred to as transdifferentiation or plasticity. These observations fueled an exciting period of discovery and high expectations followed by controversy that emerged from data suggesting cell-cell fusion as an alternate interpretation for transdifferentiation. However, data supporting stem cell plasticity are extensive and cannot be easily dismissed. Myocardial regeneration is perhaps the most widely studied and debated example of stem cell plasticity. Early reports from animal and clinical investigations disagree on the extent of myocardial renewal in adults, but evidence indicates that cardiomyocytes are generated in what was previously considered a postmitotic organ. On the basis of postmortem microscopic analysis, it is proposed that renewal is achieved by stem cells that infiltrate normal and infarcted myocardium. To further understand the role of stem cells in regeneration, it is incumbent on us to develop instrumentation and technologies to monitor myocardial repair over time in large animal models. This may be achieved by tracking labeled stem cells as they migrate into myocardial infarctions. In addition, we must begin to identify the environmental cues that are needed for stem cell trafficking and we must define the genetic and cellular mechanisms that initiate transdifferentiation. Only then will we be able to regulate this process and begin to realize the full potential of stem cells in regenerative medicine.

Detecting Acute Coronary Syndrome in the Emergency Department With Cardiac Magnetic Resonance Imaging

Background—Managing chest pain in the emergency department remains a challenge with current diagnostic strategies. We hypothesized that cardiac MRI could accurately identify patients with possible or probable acute coronary syndrome. Methods and Results—The diagnostic performance of MRI was evaluated in a prospective study of 161 consecutive patients. Enrollment required 30 minutes of chest pain compatible with myocardial ischemia but an ECG not diagnostic of acute myocardial infarction. MRI was performed at rest within 12 hours of presentation and included perfusion, left ventricular function, and gadolinium-enhanced myocardial infarction detection. MRI was interpreted qualitatively but also analyzed quantitatively. The sensitivity and specificity, respectively, for detecting acute coronary syndrome were 84% and 85% by MRI, 80% and 61% by an abnormal ECG, 16% and 95% for strict ECG criteria for ischemia (ST depression or T-wave inversion), 40% and 97% for peak troponin-I, and 48% and 85% for a TIMI risk score ≥3. The MRI was more sensitive than strict ECG criteria for ischemia (P <0.001), peak troponin-I (P <0.001), and the TIMI risk score (P =0.004), and MRI was more specific than an abnormal ECG (P <0.001). Multivariate logistic regression analysis showed MRI was the strongest predictor of acute coronary syndrome and added diagnostic value over clinical parameters (P <0.001). Conclusions—Resting cardiac MRI exhibited diagnostic operating characteristics suitable for triage of patients with chest pain in the emergency department. Performed urgently to evaluate chest pain, MRI accurately detected a high fraction of patients with acute coronary syndrome, including patients with enzyme-negative unstable angina.

Safety of Magnetic Resonance Imaging in Patients With Cardiovascular Devices An American Heart Association Scientific Statement From the Committee on Diagnostic and Interventional Cardiac Catheterization, Council on Clinical Cardiology, and the Council on Cardiovascular Radiology and Intervention: Endorsed by the American College of Cardiology Foundation, the North American Society for Cardiac Imaging, and the Society for Cardiovascular Magnetic Resonance

Advances in magnetic resonance (MR) imaging over the past 2 decades have led to MR becoming an increasingly attractive imaging modality. With the growing number of patients treated with permanent implanted or temporary cardiovascular devices, it is becoming ever more important to clarify safety issues in regard to the performance of MR examinations in patients with these devices. Extensive, although not complete, ex vivo, animal, and clinical data are available from which to generate recommendations regarding the safe performance of MR examination in patients with cardiovascular devices, as well as to ascertain caveats and contraindications regarding MR examination for such patients. Safe MR imaging involves a careful initial patient screening, accurate determination of the permanent implanted or temporary cardiovascular device and its properties, a thoughtful analysis of the risks and benefits of performing the examination at that time, and, when indicated, appropriate physician management and supervision. This scientific statement is intended to summarize and clarify issues regarding the safety of MR imaging in patients with cardiovascular devices.

Computed tomography angiography and perfusion to assess coronary artery stenosis causing perfusion defects by single photon emission computed tomography: the CORE320 study

AIMS To evaluate the diagnostic power of integrating the results of computed tomography angiography (CTA) and CT myocardial perfusion (CTP) to identify coronary artery disease (CAD) defined as a flow limiting coronary artery stenosis causing a perfusion defect by single photon emission computed tomography (SPECT). METHODS AND RESULTS We conducted a multicentre study to evaluate the accuracy of integrated CTA-CTP for the identification of patients with flow-limiting CAD defined by ≥50% stenosis by invasive coronary angiography (ICA) with a corresponding perfusion deficit on stress single photon emission computed tomography (SPECT/MPI). Sixteen centres enroled 381 patients who underwent combined CTA-CTP and SPECT/MPI prior to conventional coronary angiography. All four image modalities were analysed in blinded independent core laboratories. The prevalence of obstructive CAD defined by combined ICA-SPECT/MPI and ICA alone was 38 and 59%, respectively. The patient-based diagnostic accuracy defined by the area under the receiver operating characteristic curve (AUC) of integrated CTA-CTP for detecting or excluding flow-limiting CAD was 0.87 [95% confidence interval (CI): 0.84-0.91]. In patients without prior myocardial infarction, the AUC was 0.90 (95% CI: 0.87-0.94) and in patients without prior CAD the AUC for combined CTA-CTP was 0.93 (95% CI: 0.89-0.97). For the combination of a CTA stenosis ≥50% stenosis and a CTP perfusion deficit, the sensitivity, specificity, positive predictive, and negative predicative values (95% CI) were 80% (72-86), 74% (68-80), 65% (58-72), and 86% (80-90), respectively. For flow-limiting disease defined by ICA-SPECT/MPI, the accuracy of CTA was significantly increased by the addition of CTP at both the patient and vessel levels. CONCLUSIONS The combination of CTA and perfusion correctly identifies patients with flow limiting CAD defined as ≥50 stenosis by ICA causing a perfusion defect by SPECT/MPI.

The ClinSeq Project: Piloting large-scale genome sequencing for research in genomic medicine

ClinSeq is a pilot project to investigate the use of whole-genome sequencing as a tool for clinical research. By piloting the acquisition of large amounts of DNA sequence data from individual human subjects, we are fostering the development of hypothesis-generating approaches for performing research in genomic medicine, including the exploration of issues related to the genetic architecture of disease, implementation of genomic technology, informed consent, disclosure of genetic information, and archiving, analyzing, and displaying sequence data. In the initial phase of ClinSeq, we are enrolling roughly 1000 participants; the evaluation of each includes obtaining a detailed family and medical history, as well as a clinical evaluation. The participants are being consented broadly for research on many traits and for whole-genome sequencing. Initially, Sanger-based sequencing of 300-400 genes thought to be relevant to atherosclerosis is being performed, with the resulting data analyzed for rare, high-penetrance variants associated with specific clinical traits. The participants are also being consented to allow the contact of family members for additional studies of sequence variants to explore their potential association with specific phenotypes. Here, we present the general considerations in designing ClinSeq, preliminary results based on the generation of an initial 826 Mb of sequence data, the findings for several genes that serve as positive controls for the project, and our views about the potential implications of ClinSeq. The early experiences with ClinSeq illustrate how large-scale medical sequencing can be a practical, productive, and critical component of research in genomic medicine.