Cardiovascular molecular imaging

The recent introduction of novel gene therapies for treatment of cardiac and noncardiac diseases has caused a remarkable need for noninvasive imaging approaches to evaluate and track the progress of these therapies. In the past we have relied on the evaluation of the physiological consequences of therapeutic interventions. With advances in targeted molecular imaging we now have the ability to evaluate early molecular effects of these therapies. The development of dedicated high resolution small animal imaging systems and the establishment of transgenic animal models has enhanced our understanding of cardiovascular disease and has expedited the development of new gene therapies. Noninvasive targeted molecular imaging will allow us to directly track biochemical processes and signaling events that precede the pathophysiological changes. The examples of targeted molecular imaging outlined in this seminar provide some insight into the bright and growing future of cardiovascular molecular imaging. The success of this new field rests on the development of targeted biological markers of molecular and physiological processes, development of new instruments with improved sensitivity and resolution, and the establishment of multidisciplinary teams of experimental and clinical investigators with a wide range of expertise. Molecular imaging already plays a critical role in the experimental laboratory. We expect that, in the near future, targeted molecular imaging will be routinely used in clinical cardiovascular nuclear medicine laboratories in conjunction with existing imaging modalities for both diagnostic and prognostic purposes, as well as for evaluation of new genetic based therapeutic strategies.     

Cardiovascular molecular imaging

The goal of this review is to highlight how molecular imaging will impact the management and improved understanding of the major cardiovascular diseases that have substantial clinical impact and research interest. These topics include atherosclerosis, myocardial ischemia, myocardial viability, heart failure, gene therapy, and stem cell transplantation. Traditional methods of evaluation for these diseases will be presented first, followed by methods that incorporate conventional and molecular imaging approaches.     

Cardiovascular molecular imaging: the road ahead

Despite significant advancements in medical and device-based therapies, cardiovascular disease remains the number one cause of death in the United States. Early detection of atherosclerosis, prevention of myocardial infarction and sudden cardiac death, and modulation of adverse ventricular remodeling still remain elusive goals. Molecular imaging focuses on identifying critical cellular and molecular targets and therefore plays an integral role in understanding these biologic processes in vivo. Because many imaging targets are upregulated before irreversible tissue damage occurs, early detection could ultimately lead to development of novel, preventive therapeutic strategies. This review addresses recent work on radionuclide imaging of cardiovascular inflammation, infection, and infarct healing. We further discuss opportunities provided by multimodality approaches such as PET/MRI and PET/optical imaging.     

Cardiovascular molecular imaging of apoptosis

INTRODUCTION: Molecular imaging strives to visualise processes at the molecular and cellular level in vivo. Understanding these processes supports diagnosis and evaluation of therapeutic efficacy on an individual basis and thereby makes personalised medicine possible. APOPTOSIS AND MOLECULAR IMAGING: Apoptosis is a well-organised mode of cell suicide that plays a role in cardiovascular diseases (CVD). Apoptosis is associated with loss of cardiomyocytes following myocardial infarction, atherosclerotic plaque instability, congestive heart failure and allograft rejection of the transplanted heart. Thus, apoptosis constitutes an attractive target for molecular imaging of CVD. Our current knowledge about the molecular players and mechanisms underlying apoptosis offers a rich palette of potential molecular targets for molecular imaging. However, only a few have been successfully developed so far. AIMS: This review highlights aspects of the molecular machinery and biochemistry of apoptosis relevant to the development of molecular imaging probes. It surveys the role of apoptosis in four major areas of CVD and portrays the importance and future perspectives of apoptosis imaging. The annexin A5 imaging protocol is emphasised since it is the most advanced protocol to measure apoptosis in both preclinical and clinical studies.     

Cardiovascular MR imaging: current level of clinical activity.

Relative to other clinical magnetic resonance (MR) imaging activities, cardiovascular (CV) MR imaging has been slow to demonstrate a clinical presence. To better understand the present situation in clinical CV MR imaging, a survey of Society for Magnetic Resonance Imaging (SMRI) members was conducted. A large majority (78%) of the 90 sites responding to the survey reported clinical activity in CV MR imaging. Of these 70 sites, 46% restricted such activity to routine clinical work, while 3% restricted it to clinical research. The remaining 51% conducted both. At all clinical sites, the overall frequency of performance of clinical CV MR imaging was variable (mean, 4.2 and 13.8 cases per month at routine-only and combined routine-research sites, respectively). In clinical CV studies, gated static, multi-level spin-echo and dynamic gradient-echo (cine) techniques were most common. At the 68 sites involved in routine clinical CV MR imaging, primarily anatomic studies composed a much higher proportion of the total (mean, 86%) than primarily functional studies. The evaluation of acquired thoracic aortic disease, congenital cardiac malformation, and para- or intracardiac mass were the most prevalent anatomic indications overall. Approximately half of the same sites assessed functional aspects of CV disease. The assessment of ventricular dysfunction and valvular dysfunction were the most common functional objectives. The survey indicated that the level of clinical activities in CV MR imaging was low and that most responding sites were involved in clinical CV MR imaging primarily for detection and delineation of anatomic abnormalities.     

Diagnostic imaging of spinal trauma

The radiologist has a pivotal role in evaluation of spinal trauma patients because proper treatment cannot begin before the abnormality is diagnosed. Plain films remain the screening modality of choice, and by understanding the radiographic signs of injury, patterns produced by various traumatic mechanisms can be recognized. As radiologists we can then provide insight to our clinical colleagues into the optimal methods of further investigation. The objective is to eliminate the possibility of further damage and to identify lesions amenable to correction.     

Diagnostic imaging of craniofacial fractures

This article reviews common fractures involving the facial skeleton and describes their typical radiographic appearance. The roles of conventional radiography, supplemental projections, conventional tomography, and computed tomography are discussed. Nasofrontal, orbital, zygomatic, maxillary, and mandibular fractures are described and illustrated.     

Diagnostic imaging of bone metastases

PURPOSE: To present an "algorithm" for detection and diagnosis of skeletal metastases, which may be applied differently in symptomatic and asymptomatic cancer patients. MATERIAL AND METHODS: February to March 1999 we randomly selected and retrospectively reviewed the clinical charts of 100 cancer patients (70 women and 30 men; mean age: 63 years, range: 55-87). All the patients had been staged according to TNM criteria and had undergone conventional radiography and bone scan; when findings were equivocal, CT and MRI had been performed too. RESULTS: The primary lesions responsible for bone metastases were sited in the: breast (51 cases), colon (30 cases: 17 men and 13 women), lung (7 cases: 6 men and 1 woman), stomach (4 cases: 2 men and 2 women), skin (4 cases: 3 men and 1 woman), kidney (2 men), pleura (1 woman), and finally liver (1 men). The most frequent radiographic pattern was the lytic type (52%), followed by osteosclerotic, mixed, lytic vs. mixed and osteosclerotic vs lytic patterns. The patients were divided into two groups: group A patients were asymptomatic and group B patients had local symptoms and/or pain. DISCUSSION: Skeletal metastases are the most common malignant bone tumors: the spine and the pelvis are the most frequent sites of metastasis, because of the presence of high amounts of red (hematopoietic active) bone marrow. Pain is the main symptom, even though many bone metastases are asymptomatic. Pathological fractures are the most severe consequences. With the algorithm for detection and diagnosis of skeletal metastases two different diagnostic courses are available for asymptomatic and symptomatic patients. Bone scintigraphy remains the technique of choice in asymptomatic patients in whom skeletal metastases are suspected. However this technique, though very sensitive, is poorly specific, and thus a negative bone scan finding is double-checked with another physical examination: if the findings remain negative, the diagnostic workup is over. On the contrary, in patients with a positive bone scan or with local symptoms and pain, radiography and CT are used for screening of metastatic lesions: results may be negative (for low sensitivity of conventional radiology) or questionable (in which case bone biopsy is necessary), or else symptoms may be due to different causes than metastatic lesions (i.e., osteoarthritis). Before bone biopsy is made, MRI must be performed, because it is the only technique that allows to distinguish between bone marrow components. The limitation of MRI is the poor specificity of its findings, which may provide misleading findings.