Diabetic foot infection is the leading cause of non-traumatic lower limb amputations worldwide. In addition, diabetes mellitus and sequela of the disease are increasing in prevalence. In 2017, 9.4% of Americans were diagnosed with diabetes mellitus (DM). The growing pervasiveness and financial implications of diabetic foot infection (DFI) indicate an acute need for improved clinical assessment and treatment. Complex pathophysiology and suboptimal specificity of current non-invasive imaging modalities have made diagnosis and treatment response challenging. Current anatomical and molecular clinical imaging strategies have mainly targeted the host’s immune responses rather than the unique metabolism of the invading microorganism. Advances in imaging have the potential to reduce the impact of these problems and improve the assessment of DFI, particularly in distinguishing infection of soft tissue alone from osteomyelitis (OM). This review presents a summary of the known pathophysiology of DFI, the molecular basis of current and emerging diagnostic imaging techniques, and the mechanistic links of these imaging techniques to the pathophysiology of diabetic foot infections.

Currently, obesity is one of the leading causes death in the world. Shortly before 2000, researchers began describing metabolically active adipose tissue on cancer-surveillance ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in adult humans. This tissue generates heat through mitochondrial uncoupling and functions similar to classical brown and beige adipose tissue in mice. Despite extensive research, human brown/beige fat’s role in resistance to obesity in humans has not yet been fully delineated. FDG uptake is the de facto gold standard imaging technique when studying brown adipose tissue, although it has not been rigorously compared to other techniques. We, therefore, present a concise review of established and emerging methods to image brown adipose tissue activity in humans. Reviewed modalities include anatomic imaging with CT and magnetic resonance imaging (MRI); molecular imaging with FDG, fatty acids, and acetate; and emerging techniques. FDG-PET/CT is the most commonly used modality because of its widespread use in cancer imaging, but there are mechanistic reasons to believe other radiotracers may be more sensitive and accurate at detecting brown adipose tissue activity. Radiation-free modalities may help the longitudinal study of brown adipose tissue activity in the future.

Obesity is a leading cause of preventable death and morbidity. To elucidate the mechanisms connecting metabolically active brown adipose tissue (BAT) and metabolic health may provide insights into methods of treatment for obesity-related conditions. ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸FDG-PET/CT) is traditionally used to image human BAT activity. However, the primary energy source of BAT is derived from intracellular fatty acids and not glucose. Beta-methyl-p-iodophenylpentadecanoic acid (BMIPP) is a fatty acid analogue amenable to in vivo imaging by single photon emission computed tomography/CT (SPECT/CT) when radiolabeled with iodine isotopes. In this study, we compare the use of ¹⁸FDG-PET/CT and ¹²⁵I-BMIPP-SPECT/CT for fat imaging to ascertain whether BMIPP is a more robust candidate for the non-invasive evaluation of metabolically active adipose depots. Interscapular BAT, inguinal white adipose tissue (iWAT), and gonadal white adipose tissue (gWAT) uptake of ¹⁸FDG and ¹²⁵I-BMIPP was quantified in mice following treatment with the BAT-stimulating drug CL-316,243 or saline vehicle control. After CL-316,243 treatment, uptake of both radiotracers increased in BAT and iWAT. The standard uptake value (SUV_mean) for ¹⁸FDG and ¹²⁵I-BMIPP significantly correlated in these depots, although uptake of ¹²⁵I-BMIPP in BAT and iWAT more closely mimicked the fold-change in metabolic rate as measured by an extracellular flux analyzer. Herein, we find that imaging BAT with the radioiodinated fatty acid analogue BMIPP yields more physiologically relevant data than ¹⁸FDG-PET/CT, and its conventional use may be a pivotal tool for evaluating BAT in both mice and humans.