New technologies for human cancer imaging

Abstract

Despite technical advances in many areas of diagnostic radiology, the detection and imaging of human cancer remains poor. A meaningful impact on cancer screening, staging, and treatment is unlikely to occur until the tumor-to-background ratio improves by three to four orders of magnitude (ie, 10(3)- to 10(4)-fold), which in turn will require proportional improvements in sensitivity and contrast agent targeting. This review analyzes the physics and chemistry of cancer imaging and highlights the fundamental principles underlying the detection of malignant cells within a background of normal cells. The use of various contrast agents and radiotracers for cancer imaging is reviewed, as are the current limitations of ultrasound, x-ray imaging, magnetic resonance imaging (MRI), single-photon emission computed tomography, positron emission tomography (PET), and optical imaging. Innovative technologies are emerging that hold great promise for patients, such as positron emission mammography of the breast and spectroscopy-enhanced colonoscopy for cancer screening, hyperpolarization MRI and time-of-flight PET for staging, and ion beam-induced PET scanning and near-infrared fluorescence-guided surgery for cancer treatment. This review explores these emerging technologies and considers their potential impact on clinical care. Finally, those cancers that are currently difficult to image and quantify, such as ovarian cancer and acute leukemia, are discussed.

Fig 1.

Gompertzian growth curve of a solid tumor and its relationship to cancer detection and imaging. Number of malignant cells (ordinate) as a function of time (abscissa). The transition from first lag to log phase of growth, associated with the transition from diffusion-limited nutrition to neovascularization, is labeled “angiogenic switch.” Remission is shown as the uncertainty of cell number ranging from zero to the current clinical threshold for cancer detection (approximately 10⁹ cells growing as a single mass).

Fig 2.

Three-dimensional development of exogenous, targeted diagnostic or therapeutic agents. Colored box delineates optimal in vivo performance.

Fig 3.

Intraoperative image-guidance using invisible near-infrared (NIR) fluorescent light. Indocyanine green (ICG) mixed with human serum albumin (HSA) creates a sensitive lymphatic tracer (ICG:HSA) of 7 nm in hydrodynamic diameter. After injection (Inj) into the parenchyma of swine colon, lymphatic channels (LCs) are seen within seconds, and within 1 to 2 minutes, the sentinel lymph node (SLN) has been identified (top) and can be resected under image guidance (bottom). Shown for each are the color video (left), 800-nm NIR fluorescence (middle), and merged images (pseudocolored in green; right) of the two. Arrow shows the direction of lymph flow. All images are refreshed at 15 Hz using a previously described intraoperative NIR fluorescence imaging system.