Small-Animal Molecular Imaging Methods

Abstract

Rationale The ability to trace or identify specific molecules within a specific anatomic location provides insight into metabolic pathways, tissue components and tracing of solute transport mechanisms. With the increasing use of small animals for research such imaging must have sufficiently high spatial resolution to allow anatomic localization as well as sufficient specificity and sensitivity to provide an accurate description of the molecular distribution and concentration. Methods Imaging methods based on electromagnetic radiation, such as PET, SPECT, MRI and CT, are increasingly applicable due to recent advances in novel scanner hardware, image reconstruction software and availability of novel molecules which have enhanced sensitivity in these methodologies. Results Micro-PET has been advanced by development of detector arrays that provide higher resolution and positron emitting elements that allow new molecular tracers to be labeled. Micro-MRI has been improved in terms of spatial resolution and sensitivity by increased magnet field strength and development of special purpose coils and associated scan protocols. Of particular interest is the associated ability to image local mechanical function and solute transport processes which can be directly related to the molecular information. This is further strengthened by the synergistic integration of the PET with MRI. Micro-SPECT has been improved by use of coded aperture imaging approaches as well as image reconstruction algorithms which can better deal with the photon limited scan data. The limited spatial resolution can be partially overcome by integrating the SPECT with CT. Micro-CT by itself provides exquisite spatial resolution of anatomy, but recent developments of high spatial resolution photon counting and spectrally-sensitive imaging arrays, combined with x-ray optical devices, have promise for actual molecular identification by virtue of the chemical bond lengths of molecules, especially of bio-polymers. Conclusion With the increasing use of small animals for evaluating new clinical imaging techniques as well as providing increased insights into patho-physiological phenomena, the availability of improved detection systems, scanning protocols and associated software, the repertoire of molecular imaging is greatly increased in sensitivity and specificity.

A View on Imaging in Drug Research and Development for Respiratory Diseases

“…Table 1 provides an overview of current imaging modalities of interest for imaging the lungs. Refer to other reviews for detailed descriptions of each method for small-animal applications (Beckmann et al, 2007a,b;De Kemp et al, 2010) or human applications (Harris and Schuster, 2007;Petersson et al, 2007;Ley-Zaporozhan et al, 2008a;Sundaram et al, 2010). In many respects the imaging techniques are complementary; there is no "all-in-one" imaging modality providing optimal sensitivity, specificity, and temporo-spatial resolution.…”

Tumor glucose metabolism imagedin vivoin small animals with whole-body photoacoustic computed tomography

“…In this report, we have demonstrated that RC-PACT provided tumor glucose metabolism and anatomic images with ultrasound-defined spatial resolution in a single imaging modality. While PET-CT and PET-MRI have been well established in the field, 3 RC-PACT is a promising and less expensive alternative with the advantages of non-ionizing laser radiation, non-radioactive optical contrast, and endogenous hemoglobin contrast. Additionally, image co-registration of anatomical and metabolic assessments is automatic.…”

Imaging in animal models

“…Similar to CT, micro-MRI has a high spatial resolution and has wide applications of use including functional, anatomical and molecular imaging [10]. The advantage of micro-MRI is that it provides excellent soft tissue resolution between 100-200 µm [11] and even up to 50 µm [12] in high strength magnetic fields, allowing imaging of tumour growth and development. Another strength of MRI is its sensitivity to biological processes including perfusion and flow, enabling imaging of tumour vasculature.…”

“…Due to these disadvantages, there is increasing emphasis on multimodal imaging such as micro-CT/MRI although this impractical for many laboratories due to cost and need for specialist equipment. However, newer generation PET scanners are in development with higher resolution of around 1 μl [11]. Further advances are expected in this field with refinement of the technology, to improve imaging of tumour cell response to therapeutic agents.…”