Olga James

Detection of Left Ventricular Thrombus by Delayed-Enhancement Cardiovascular Magnetic Resonance : Prevalence and Markers in Patients With Systolic Dysfunction

OBJECTIVES This study sought to assess the prevalence and markers of left ventricular (LV) thrombus among patients with systolic dysfunction. BACKGROUND Prior studies have yielded discordant findings regarding prevalence and markers of LV thrombus. Delayed-enhancement cardiovascular magnetic resonance (DE-CMR) identifies thrombus on the basis of tissue characteristics rather than just anatomical appearance and is potentially highly accurate. METHODS Prevalence of thrombus by DE-CMR was determined in 784 consecutive patients with systolic dysfunction (left ventricular ejection fraction [LVEF] <50%) imaged between July 2002 and July 2004. Patients were recruited from 2 separate institutions: a tertiary-care referral center and an outpatient clinic. Comparison to cine-cardiovascular magnetic resonance (CMR) was performed. Follow-up was undertaken for thrombus verification via pathology evaluation or documented embolic event within 6 months after CMR. Clinical and imaging parameters were assessed to determine risk factors for thrombus. RESULTS Among this at-risk population (age 60 +/- 14 years; LVEF 32 +/- 11%), DE-CMR detected thrombus in 7% (55 patients) and cine-CMR in 4.7% (37 patients, p < 0.005). Follow-up was consistent with DE-CMR as a better reference standard than cine-CMR, including 100% detection among 5 patients with thrombus verified by pathology (cine-CMR, 40% detection), and logistic regression analysis testing the contributions of DE-CMR and cine-CMR simultaneously, which showed that only the presence of thrombus by DE-CMR was associated with follow-up end points (p < 0.005). Cine-CMR generally missed small intracavitary and small or large mural thrombus. In addition to traditional indices such as low LVEF and ischemic cardiomyopathy, multivariable analysis showed that increased myocardial scarring, an additional parameter available from DE-CMR, was an independent risk factor for thrombus. CONCLUSIONS In a broad cross section of patients with systolic dysfunction, thrombus prevalence was 7% by DE-CMR and included small intracavitary and small or large mural thrombus missed by cine-CMR. Prevalence increased with worse LVEF, ischemic etiology, and increased myocardial scarring.

Prevalence of Regional Myocardial Thinning and Relationship With Myocardial Scarring in Patients With Coronary Artery Disease

IMPORTANCE Regional left ventricular (LV) wall thinning is believed to represent chronic transmural myocardial infarction and scar tissue. However, recent case reports using delayed-enhancement cardiovascular magnetic resonance (CMR) imaging raise the possibility that thinning may occur with little or no scarring. OBJECTIVE To evaluate patients with regional myocardial wall thinning and to determine scar burden and potential for functional improvement. DESIGN, SETTING, AND PATIENTS Investigator-initiated, prospective, 3-center study conducted from August 2000 through January 2008 in 3 parts to determine (1) in patients with known coronary artery disease (CAD) undergoing CMR viability assessment, the prevalence of regional wall thinning (end-diastolic wall thickness ≤5.5 mm), (2) in patients with thinning, the presence and extent of scar burden, and (3) in patients with thinning undergoing coronary revascularization, any changes in myocardial morphology and contractility. MAIN OUTCOMES AND MEASURES Scar burden in thinned regions assessed using delayed-enhancement CMR and changes in myocardial morphology and function assessed using cine-CMR after revascularization. RESULTS Of 1055 consecutive patients with CAD screened, 201 (19% [95% CI, 17% to 21%]) had regional wall thinning. Wall thinning spanned a mean of 34% (95% CI, 32% to 37% [SD, 15%]) of LV surface area. Within these regions, the extent of scarring was 72% (95% CI, 69% to 76% [SD, 25%]); however, 18% (95% CI, 13% to 24%) of thinned regions had limited scar burden (≤50% of total extent). Among patients with thinning undergoing revascularization and follow-up cine-CMR (n = 42), scar extent within the thinned region was inversely related to regional (r = -0.72, P < .001) and global (r = -0.53, P < .001) contractile improvement. End-diastolic wall thickness in thinned regions with limited scar burden increased from 4.4 mm (95% CI, 4.1 to 4.7) to 7.5 mm (95% CI, 6.9 to 8.1) after revascularization (P < .001), resulting in resolution of wall thinning. On multivariable analysis, scar extent had the strongest association with contractile improvement (slope coefficient, -0.03 [95% CI, -0.04 to -0.02]; P < .001) and reversal of thinning (slope coefficient, -0.05 [95% CI, -0.06 to -0.04]; P < .001). CONCLUSIONS AND RELEVANCE Among patients with CAD referred for CMR and found to have regional wall thinning, limited scar burden was present in 18% and was associated with improved contractility and resolution of wall thinning after revascularization. These findings, which are not consistent with common assumptions, warrant further investigation.

Utility of FDG PET/CT in Inflammatory Cardiovascular Disease

Inflammatory disorders of the cardiovascular system can affect the myocardium, pericardium, or vessel walls. Patients with myocardial and pericardial disease may present with chest pain, palpitations, and shortness of breath, symptoms resembling myocardial ischemia or infarction. The manifestations of vasculitis may include fever, weight loss, and fatigue, mimicking infectious or malignant processes. Because of the difficulty of differentiating these disease processes, patients frequently undergo multiple diagnostic examinations before obtaining a final diagnosis of myocarditis, pericarditis, or vasculitis. Computed tomography (CT) and magnetic resonance imaging play important roles in the assessment of structural abnormalities of the cardiovascular system, and combined positron emission tomography (PET) and CT may depict inflammatory processes before structural changes occur. Familiarity with the PET/CT appearances of inflammatory processes in the myocardium, pericardium, and vessels is important for accurate and prompt diagnosis.

PET Imaging of Tau Pathology in Alzheimer’s Disease and Tauopathies

Alzheimer’s disease (AD) is a major public health problem affecting nearly 35 million people worldwide with numbers projected to rise to 115.4 million by 2050. Medicare and Medicaid cost of AD is anticipated to increase fourfold to approximately

Cortical β-amyloid levels and neurocognitive performance after cardiac surgery.

600 billion in the next 40 years. AD is the only cause of death among the top 10 causes that has no prevention or cure (1, 2). AD causes are not fully known and clinical drug trials have a greater than 90% failure rate. There is an urgent need to find accurate methods of early detection as well as effective therapies before patients with AD develop significant brain damage. Clinical diagnosis of AD remains a challenge since there are no validated tests for an affirmative diagnosis and dozens of conditions can mimic it. Hallmarks of AD brain are numerous neurons with neurofibrillary tangles of paired helical filaments (PHFs), straight filaments, and extracellular deposits of β-amyloid as the major component of senile (neuritic) plaques in the brain. Definitive diagnosis of AD is made only after an autopsy or biopsy. While AD is the most common cause of dementia in the elderly, accounting for approximately 50–70% of cases, many other causes of dementia can mimic and overlap with AD clinical presentation. Vascular dementia, mixed dementia of vascular and Alzheimer’s etiology, dementia with Lewy bodies (DLB), and frontotemporal dementias are some examples with overlapping clinical and diagnostic features. Clinical diagnosis of probable AD is currently made by excluding other causes using history, exam and labs, structural imaging, and cognitive testing. However, their accuracy is suboptimal. For example, a clinical-autopsy correlative study of more than 900 cases seen at leading academic memory centers found that some 40% of patients clinically diagnosed with non-AD dementia had postmortem histopathology consistent with AD (3). Likewise, nearly 30% of patients, who were thought to have AD, clinically do not meet postmortem pathologic criteria for AD (3). In recent clinical drug trials of mild to moderate AD, it is also estimated that about 30% of patients did not have AD pathology thus making it difficult to determine if failures were due to ineffective drug versus diagnostic errors (4). There is a call for the development and integration of pathologic biomarkers into routine clinical evaluation to establish revised diagnostic criteria for clinical and preclinical AD. Such markers may not only assist with an accurate affirmative diagnosis of AD and disease staging, but may also accelerate drug development (5). Molecular imaging, specifically positron emission tomography (PET), is a promising modality for early detection and disease staging in Alzheimer’s patients. Recently approved amyloid PET tracers (e.g., F-18 florbetapir, F-18 flutemetamol) can detect cortical fibrillary β-amyloid (6). A negative amyloid scan substantially decreases the odds of a person having AD and can impact clinical decision making or treatment. In at-risk subjects, a positive amyloid scan is associated with a threefold greater risk of converting to dementia (7). The limitations of amyloid imaging are that amyloid plaques by themselves are insufficient for a positive diagnosis of AD. Thus, the advent of a PET taupathology tracer may serve as a complimentary tool to aid in affirmative diagnosis, as well as in disease staging. Given the number of tau-based therapies being developed, a tau-PET tracer would also allow for a selection of pathology-positive individuals and monitor the effectiveness of therapy.

Patient and tumor characteristics predictive of an elevated hepatopulmonary shunt fraction before radioembolization of hepatic tumors.

Introduction Neurological and neurocognitive dysfunction occurs frequently in the large number of increasingly elderly patients undergoing cardiac surgery every year. Perioperative cognitive deficits have been shown to persist after discharge and up to several years after surgery. More importantly, perioperative cognitive decline is predictive of long-term cognitive dysfunction, reduced quality of life and increased mortality. The proposed mechanisms to explain the cognitive decline associated with cardiac surgery include the neurotoxic accumulation of β-amyloid. This study will be the first to provide molecular imaging to assess the relationship between neocortical β-amyloid deposition and postoperative cognitive dysfunction. Methods and analysis 40 patients providing informed consent for participation in this Institutional Review Board-approved study and undergoing cardiac (coronary artery bypass graft (CABG), valve or CABG+valve) surgery with cardiopulmonary bypass will be enrolled based on defined inclusion and exclusion criteria. At 6 weeks after surgery, participants will undergo 18F-florbetapir positron emission tomography imaging to assess neocortical β-amyloid burden along with a standard neurocognitive battery and blood testing for apolipoprotein E ε-4 genotype. Results The results will be compared to those of 40 elderly controls and 40 elderly patients with mild cognitive impairment who have previously completed 18F-florbetapir imaging. Ethics and dissemination This study has been approved by the Duke University Institutional Review Board. The results will provide novel mechanistic insights into postoperative cognitive dysfunction that will inform future studies into potential treatments or preventative therapies of long-term cognitive decline after cardiac surgery.

Resolution recovery and noise regularization in nuclear cardiology

ObjectiveTo determine whether any patient or hepatic tumor characteristics are predictive of hepatopulmonary shunt fraction when performed before radioembolization. Materials and methodsA retrospective review was performed on 190 patients who underwent preradioembolization hepatic arteriography with calculation of hepatopulmonary shunt fraction using technetium-99m-labeled macroaggregated albumin perfusion scintigraphy. Patient and tumor characteristics including imaging features were reviewed for correlation with absolute shunt fraction, shunt fraction greater than 10%, and shunt fraction greater than 20%. ResultsMost tumor types showed some cases of elevated shunt fraction greater than 10%. Six patients had a shunt fraction greater than 20%: four were hepatocellular carcinoma and two were neuroendocrine tumor metastases. Univariate analysis showed that dominant tumor diameter, hepatic tumor burden, vascular invasion, hepatic venous invasion, and hypervascularity on angiography were associated with a shunt fraction greater than 10%. Only dominant tumor diameter and vascular invasion were associated with a shunt fraction greater than 20%. On multivariate analysis, only tumor diameter (odds ratio 1.2) and hepatic venous invasion (odds ratio 23.0) were associated independently with an increased shunt fraction greater than 10%. ConclusionMultiple patient and tumor-related characteristics were significantly correlated with the hepatopulmonary shunt fraction on univariate analysis. However, on multivariate analysis, only the dominant tumor diameter and presence of hepatic venous invasion were associated independently with a greater than 10% shunt fraction.

Phase-1 Clinical Trial Results of High-Specific-Activity Carrier-Free 123I-Iobenguane

Radionuclide myocardial perfusion imaging (MPI) is one of the most established and validated diagnostic modalities in the evaluation of patients with hemodynamically significant coronary artery disease (CAD). Growing public awareness and media attention toward the radiation exposure raised appropriate concerns related to the potential harmful effects of the radionuclide use. In 2010, American Society of Nuclear Cardiology (ASNC) issued a statement titled ‘‘Recommendations for reducing radiation exposure in myocardial perfusion imaging’’ addressing these issues. The use of appropriateness criteria for MPI, decreased radiotracer activity administration, utilization of newer solid state cameras, and novel image reconstruction are some of the ways to diminish ionizing radiation exposure in patients and healthcare professionals. This article will address image reconstruction possibilities for myocardial perfusion imaging (Figures 1, 2). The traditional method of image reconstruction in nuclear cardiology has been filtered backprojection (FPB). Its drawbacks are relatively lesser quality, lowcount SPECT (single-photon emission computerized tomography) images related to amplified noise, and inability to correct for photon attenuation and scatter. This reconstruction algorithm does not compensate for the limitations related to the detector, such as collimator geometry and distance from the emitting source. FBP images are prone to blurring and star artifacts, requiring filtering prior to backprojection, potentially decreasing imaging resolution. Low-count images in FBP preclude a further decrease in radiopharmaceutical administration. This limits the ability to diminish the effective radiation dose to the patient as a result, requiring longer acquisition times, which may lead to motion artifacts due to poor patient cooperation. Ideally, the reconstruction method should allow the lowest amount of radiopharmaceutical without loss of image quality and diagnostic accuracy. Following significant improvements in the computational processing power, iterative reconstruction, namely maximal likelihood expectation maximization (MLEM) technique, replaced FBP over a decade ago. Another addition to the iterative method was an introduction of ordered subset expectation maximization (OSEM). It uses a subset of the data at each iteration, producing a faster rate of conversion. OSEM reconstructions allow the detector variables to be incorporated, also attenuation correction maps, scatter, and the variation between source and detector positions. Resolution recovery reconstruction method addresses noise reduction and resolution recovery simultaneously for low-count density data. A statistically based noise suppression algorithm is applied to the images, allowing quality improvement. At the present time, there are several iterative reconstruction packages available on the market: Evolution (GE healthcare, Milwaukee, WI, USA), widebeam reconstruction (UltraSPECT, Haifa, Israel), Astonish (Phillips), Flash 3D (Siemens), and nSPEED (Digirad), all offering resolution recovery and noise reduction. Wide-beam reconstruction incorporates resolution recovery and controls noise during the reconstruction process. The modification is done without applying the post-processing filter and is a great adjunct tool for the low-count statistics studies with inherently higher noise level. It is an iterative reconstruction method designed to focus on resolution recovery and noise reduction at the same time, therefore helping improve image quality in studies with significantly less photon counts. This technology incorporates the physics and geometry modeling of the emission and detection process. There are several factors such modeling focuses on. First, pixel-voxel weighting values are aligned to the Reprint requests: Olga James, MD, Duke University Medical Center, Durham, NC; olga.g.james@dm.duke.edu J Nucl Cardiol 2017;24:138–41. 1071-3581/

Two-day lymphoscintigraphic imaging for melanoma.

34.00 Copyright 2016 American Society of Nuclear Cardiology.

18F-florbetapir Positron Emission Tomography–determined Cerebral β-Amyloid Deposition and Neurocognitive Performance after Cardiac Surgery

A first-in-human phase 1 clinical study was performed on 12 healthy adults with a high-specific-activity carrier-free formulation of 123I-iobenguane. Clinical data are presented on the behavior of this receptor-targeting imaging agent. Methods: Whole-body and thoracic planar and SPECT imaging were performed over 48 h for calculation of tissue radiation dosimetry and for evaluation of clinical safety and efficacy. Results: A reference clinical imaging database acquired over time for healthy men and women injected with high-specific-activity 123I-iobenguane showed organ distribution and whole-body retention similar to those of conventional 123I-iobenguane. The heart-to-mediastinum ratios for the high-specific-activity formulation were statistically higher than for conventional formulations, and the predicted radiation dosimetry estimations for some organs varied significantly from those based on animal distributions. Conclusion: Human normal-organ kinetics, radiation dosimetry, clinical safety, and imaging efficacy provide compelling evidence for the use of high-specific-activity 123I-iobenguane.