Tim Wollenweber

Characterizing the Inflammatory Tissue Response to Acute Myocardial Infarction by Clinical Multimodality Noninvasive Imaging

Background—Myocardial infarction (MI) triggers a systemic inflammatory response which determines subsequent healing. Experimentally, cardiac positron emission tomography and magnetic resonance imaging have been used successfully to obtain mechanistic insights. We explored the translational potential in patients early after MI. Methods and Results—Positron emission tomography/computed tomography and cardiac magnetic resonance were performed in 15 patients <7 days after first MI. Cardiac magnetic resonance showed regional transmural late gadolinium enhancement and edema exceeding the area of late gadolinium enhancement. Using F-18 deoxyglucose with heparin pretreatment, metabolic rate of glucose (MRGlc) was significantly increased in infarct versus remote myocardium (median, 2.0 versus 0.4 mg/min per 100 mL; P=0.0001). MRGlc in infarct correlated with remote myocardium (&rgr;=0.64; P=0.01), spleen (&rgr;=0.82; P=0.0002), and bone marrow(&rgr;=0.57; P=0.03), but not with muscle or liver. Regionally, F-18 deoxyglucose score was highest in segments with late gadolinium enhancement versus edema only and remote (median, 2.0 versus 1.8 versus 0.4; P<0.0001). Patients requiring repeat intervention during preliminary follow-up of 11±5 months tended to have higher early post-MI MRGlc. Five patients with chronic, stable MI served as controls. Opposite to acute MI, MRGlc was lower in infarct (median infarct/remote ratio, 0.6 versus 3.2 for acute MI; P=0.001), and there was no correlation with bone marrow or spleen MRGlc. Conclusions—Increased glucose utilization after heparin-induced suppression of myocyte uptake appears to mostly reflect inflammatory activity in damaged myocardium early after MI. Consistent with prior preclinical observations, and in contrast to chronic MI, this is associated with activity in spleen and bone marrow as sources of inflammatory cells. Positron emission tomography and cardiac magnetic resonance multimodality characterization of the acutely infarcted, inflamed myocardium may provide multiparametric end points for clinical studies aiming at support of infarct healing.

Simultaneous dual-isotope solid-state detector SPECT for improved tracking of white blood cells in suspected endocarditis.

Aims High-energy resolution and sensitivity of novel cadmium-zinc-telluride (CZT) detector equipped SPECT systems facilitate simultaneous imaging of multiple isotopes and may enhance the detection of molecular/cellular signals. This may refine the detection of endocarditis. This study was designed to determine the feasibility and diagnostic accuracy of simultaneous imaging of inflammation with 111In-labeled white blood cells (WBCs) and myocardial perfusion with 99mTc-sestamibi, for localization of WBCs relative to the valve plane in suspected endocarditis. Methods and results A dedicated cardiac CZT camera (Discovery 530c, GE Healthcare) was employed. Anthropomorphic thorax phantom studies were followed by clinical studies in 34 patients with suspected infection of native valves (n = 12) or implants (n = 22). Simultaneous 111In-WBC/99mTc perfusion imaging was performed, and compared with standard 111In-WBC planar scintigraphy and SPECT-CT. Phantom studies ruled out significant radioisotope crosstalk. Downscatter on 99mTc images was not observed for 111In activity as high as 2.5*99mTc activity. In patients, image quality was superior for CZT imaging vs. conventional SPECT-CT and planar scintigraphy (P < 0.01). Cadmium-zinc-telluride dual isotope imaging improved reader confidence for detection of inflammatory foci. Diagnostic accuracy based on surgery or Duke Criteria during follow-up was highest for CZT imaging (P < 0.001). Conclusion Novel CZT SPECT technology improves the accuracy of molecular/cellular cardiac imaging. Simultaneous multi-isotope imaging with 111In and 99mTc is feasible and aids in the workup of suspected endocarditis.

Cardiac Molecular Imaging

Molecular imaging enables the visualization and interrogation of specific biologic targets and pathways that precede or underlie changes in morphology, physiology, and function of the heart. Accordingly, it aims at identifying precursors or early stages of cardiac disease, and it may facilitate monitoring and guidance of novel, increasingly specific and versatile cardiovascular therapies. Although SPECT and PET imaging of myocardial metabolism and autonomic innervation are already embedded in clinical practice, various additional targets, probes, and techniques are under development. These techniques hold promise to become a future key in personalizing cardiovascular care.

Molecular imaging to predict ventricular arrhythmia in heart failure

Ventricular tachycardia (VT) is a major cause of sudden cardiac death (SCD) in patients with heart failure (HF). Left ventricular ejection fraction (LVEF) and heart failure class according to the New York Heart association (NYHA) are in most common use to identify patients that may benefit from implantable cardioverter defibrillator (ICD) therapy. But during 3 years of follow up only 35% of patients receive appropriate ICD action. Therefore, there is a continued need for refinement of selection criteria for ICD implantation. In this regard, molecular imaging of the autonomic nervous system, which plays a central role in HF progression and cardiac electro-mechanical regulation, can make a substantial contribution. This article reviews the currently available literature concerning the value of molecular neuronal cardiac imaging for prediction of ventricular arrhythmias in HF patients.

The axial charge of the nucleon on the lattice and in chiral perturbation theory

We present recent Monte Carlo data for the axial charge of the nucleon obtained by the QCDSF-UKQCD collaboration for N_f=2 dynamical quarks. We compare them with formulae from chiral perturbation theory in finite and infinite volume and find a remarkably consistent picture.