Radiologic and near-infrared/optical spectroscopic imaging: where is the synergy?

Abstract

Objective: Optical and radiologic imaging are commonly used in preclinical research, and research into combined instruments for human applications is showing promise. The purpose of this article is to outline the fundamental limitations and advantages and to review the available systems. The emerging developments and future potential will be summarized.

Conclusion: Integration of hybrid systems is now routine at the preclinical level and appears in the form of specialized packages in which performance varies considerably. The synergy is commonly focused on using spatial localization from radiographs to provide structural data for spectroscopy; however, applications also exist in which the spectroscopy informs the use of radiologic imaging. Examples of clinical systems under research and development are shown.

Fig. 1

Conceptual schematic shows how different imaging techniques compare in terms of their sensitivity to low molecular concentrations. In particular, radiography can image down to millimolar levels and is mostly used to resolve one agent at time, whereas near-infrared (NIR)/optical fluorescence imaging is sensitive to micromolar to nanomolar concentrations and has potential to image up to 10 agents simultaneously.

Fig. 2. Attenuation spectra for radiography and optical/near-infrared (NIR)

A and B, Graphs show spectra for radiology (A) and optical/near-infrared (NIR) (B) in terms of constituents in most tissues. X-ray attenuation is dominated by photoelectric effect absorption, which increases exponentially at lower energies. NIR/visible wavelengths are dominated by elastic scatter, and window of very low absorption occurs from 620 to 1,050 nm, sometimes referred to as diffuse transmission window of tissue. Molecular constituents of tissue in NIR/visible imaging provide significantly stronger absorption peaks that allow molecular spectroscopy of tissue. Hb = hemoglobin.

Fig. 3. Spectra of contrast available

A and B, Graphs show spectra of contrast available in radiography (A) and near-infrared (NIR) fluorescence (B). Contrast from iodinated agents or barium in attenuating x-rays is dominated by enhanced photoelectric effect in 10–200 keV range due to both K-edge effects and general increase in overall absorption of x-rays. Range of organic or biocompatible fluorophores is illustrated with some representative agents in B including protoporphyrin IX, cyanine dyes Cy5.5 and C7, and indocyanine green. Z is atomic number of the element.

Fig. 4. Examples of various systems

A, Example images from Carestream system with radiographic projection and fluorescence within gastrointestinal tract and overlay. This instrument was first system developed for hybrid radiographic/optical fluorescence imaging of mice. B, Photograph shows newly released Quantum radiographic tomography and optical tomography system from Caliper Biosciences. C, Example images from optical tomography combined with radiographic CT are shown for glioma tumor imaged with contrast from endogenously induced fluorescence from protoporphyrin IX within tumor. D, VisEn Medical Systems instrument features animal cassette that allows optical and radiographic tomography in same holder.

Fig. 5. Breast imaging systems

A, Photograph shows SoftScan (ART, Inc.) breast imaging system. B and C, Representative images of total hemoglobin concentration (B) and reduced scatter coefficient (C) images acquired by SoftScan system are shown along with corresponding radiologic images of breast. D, Photograph shows CT Laser Mammography (IMDS Inc.) breast imaging hardware. E and F, Representative images of total hemoglobin concentration are shown along with corresponding radiologic images of breast. G, Photograph of Tomosynthesis/Optical Breast Imaging (TOBI) system from Massachusetts General Hospital. (Copyright IEEE Publishing) H and I, Representative total hemoglobin concentration images are shown along with coregistered tomosynthesis images in plane of interest. (Copyright IEEE Publishing)