Structural and functional imaging of muscle, heart, endocrine pancreas and kidneys in cardiometabolic drug development

Abstract

Introduction Non-invasive imaging is well established in clinical disciplines including neuroscience, respiratory, oncology and cardiovascular medicine. In contrast, the use of imaging in drug development for metabolic diseases, e.g., type 1 and type 2 diabetes, has been less prominent. In part, this difference reflects the fact that imaging has not been a routine method for the clinical assessment of the status of patients with diabetes, which relies more on circulating biomarkers such as glucose and glycated haemoglobin. In contrast to much of the use of imaging in clinical medicine that is used to inform diagnosis and therapeutic decisions, imaging in drug development aims to monitor a change over time of a continuous variable. In recent years, imaging has become more widely used in some aspects of metabolic drug development, notably in the assessment of body composition and nonalcoholic fatty liver disease (NAFLD) where the quest for non-invasive imaging to replace invasive liver biopsy is a major objective. In other metabolic disorders, imaging can provide useful complementary information to other biomarkers. Recent data from major clinical trials of sodium-glucose co-transporter-2 inhibitors and glucagon like peptide-1 receptor agonists have demonstrated unexpected cardioprotective and renoprotective properties. Imaging is well suited to studying the effects of new diabetes drugs on clinical outcomes including atherosclerotic cardiovascular events, heart failure, and renal function. This chapter focuses on recent innovations in non-invasive imaging of the pancreas, skeletal muscle, adipose tissue, kidney, and heart. Key Methods Many of the methods, e.g. ultrasound (US), computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET) are broadly familiar to clinicians and clinical scientists. Each has advantages and limitations with respect to their application to drug development. These include the pathophysiological relevance of the imaging, accuracy, suitability for repeated studies in the context of clinical trials, cost, and availability of expertise in application and interpretation. Several of these imaging methodologies have evolved or have been combined with other investigative techniques to provide additional functional assessments that may be of value in future drug development. Imaging techniques are gaining greater prominence in drug development for diabetes and the microvascular and macrovascular complications of diabetes. Hybrid imaging systems, e.g. PET/ CT and PET/MRI, are becoming more widely available and offer opportunities to combine detailed morphological imaging with functional and molecular imaging.