13-06 Molecular Imaging

Definition. Catchwords like personalized medicine are fashionable. Molecular imaging is another one, a misnomer used as an umbrella term for all biological and medical imaging technologies and methods that aim at picturing anatomy, histology as well as features and processes at the cellular and molecular level [re­view articles: ⇒ James, ⇒ Weissleder]. It is basically an extension of ra­dio­iso­tope tracer scanning and imaging into other fields of medical imaging. Com­mon­ly, molecular imaging is just a synonym of contrast-enhanced imaging. Mo­le­cu­lar imaging media are contrast agents of one kind or another (plain contrast en­han­cers, static tracers, or responsive agents).

However, although MR imaging does not possess sufficient sensitivity to ima­ge single molecules, responsive MR agents can dynamically change one or more of their physicochemical properties when interacting with their intended mo­le­cu­lar biomarker. A good review of responsive MR agents has been published by Hingorani, Bernstein, and Pagel [⇒ Hingorani].

Given the increasing understanding of molecular mechanisms of disease and the development of innovative therapies at the genetic level, molecular imaging is aimed at the exploitation of specific molecules as the source of image contrast (Figure 13-18). For the time being, clinical molecular imaging will stay in the realm of radioisotope scanning and contrast-agent enhanced imaging, some­times related to hybrid systems such as PET/MRI or PET/CT.

Figure 13-18: (a) Whole body screening: radioisotope scan; (b) organ level: MR spine study without con­trast enhancement; (c) tissue level: bone histology; (d) genetic level: chromosome screening. At the organ level, diagnostic imaging to­day is able to visualize gross parameters of disease and to describe, e.g., tumor bur­den. In the future, it will be possible to mark tumors and to target drugs as well as contrast agents. At the genetic level researchers hope to highlight genetic mu­ta­tions and thus perform gene targeting and therapy.

Researchers will try to leave some of the existing pathways in contrast agent and tracer development. Instead of looking for relatively gross parameters of disease, they will try to explore beyond the tissue level on the cell or even the molecular level. They will try to connect diagnosis with therapy; one of the main goals being the imaging assessment of therapeutic effectiveness at the molecular level, long before phenotypic changes occur [⇒ Weissleder 1999].

Magnetic Resonance Imaging and Molecular Imaging. MEMRI (manganese enhanced MRI) of the heart is a good example of one of the few promising mo­le­cu­lar imaging methods, because the same manganese-based compound can be used for diagnostics and treatment of, e.g., myocardial infarctions, cancer, and drug intoxication (theragnostic properties), is inexpensive, and addresses a mass market.

In general however, whereas the spatial resolution of MR imaging is very good, its sensitivity is low and thus limiting. Present software and hardware im­pro­ve­ments, such as more sophisticated coil design, seem not to be able to bridge the existing gap. Any increase of field strength beyond today's ultrahigh fields (3 Tesla) to gain crucial signal strength is restricted by the specific absorption rate (SAR) and by potential side effects of the magnetic fields. A detour would possibly be the use of hyperpolarization; however, hy­per­po­la­riz­ed clinical ventilation imaging was not promising and abandonded for com­mer­cial reasons.

Intelligent agents might be feasible in magnetic resonance imaging. They could alter their relaxivity according to local temperature, pH, or chemical ac­ti­vi­ty. There are a lot of uncertainties in this kind of research, and with the advent of in vitro screening techniques such as easy-to-use blood test for Alzheimer's di­sea­se, molecular imaging will be increasingly challenged. However, molecular imaging will remain one of the major R&D topics in diagnostic and therapeutic imaging and contrast agent research of the coming decades.

How molecular is "molecular imaging"?
When will it reach clinical routine?
A comment.