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Scaling down imaging: molecular mapping of cancer in mice

Nature Reviews Cancer volume 2, pages 11–18 (2002)Cite this article

Key Points

  • Traditional approaches of monitoring cancer growth in mouse models have largely used surface-implanted tumours and caliper measurements.

  • A variety of non-invasive high-resolution imaging methods are now available for the detection and monitoring of deep-seated cancers, as well as their metastases, in transgenic models.

  • Magnetic resonance imaging (MRI) and computed tomography (CT) are primarily used to display internal anatomy of mouse models and are useful tools for phenotyping.

  • The availability of radioisotope, magnetic and/or fluorescent tags is continuously improving our ability to image specific molecular markers in vivo.

  • The use of 'smart' sensors for MRI and optical imaging holds particular promise in sensing and reporting molecular signatures.

  • Technologies are being developed that will ultimately allow cellular protein and signal-pathway profiling. This will further extend our understanding of the molecular pathology of cancer, speed up drug development and can lead to patient-tailored therapies.

Abstract

The development of miniaturized imaging equipment and reporter probes has improved our ability to study animal models of disease, such as transgenic and knockout mice. These technologies can now be used to continuously monitor in vivo tumour development, the effects of therapeutics on individual populations of cells, or even specific molecules. If these techniques prove effective in mice, they might be translated into the clinic in the future, where they could be used to non-invasively detect and monitor treatment of human cancers.

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Figure 1: Mouse computed tomography imaging.
Figure 2: Optical imaging.
Figure 3: Fluorescence-mediated tomography.

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Authors and Affiliations

  1. Harvard Medical School, Center for Molecular Imaging Research, Massachusetts General Hospital, Boston, 02129, Massachusetts, USA

    Ralph Weissleder

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  1. Ralph Weissleder
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DATABASES

CancerNet:

bladder tumours

bone tumours

brain tumour

breast cancer

colon cancer

prostate cancer

 LocusLink:

bombesin receptor

caspases

cathepsins

cathepsin B

cathepsin D

ERBB2

E-selectin

folate receptor

MMP

MMP-2

somatostatin

thymidine kinase

transferrin receptor

FURTHER INFORMATION

Berkeley Labs, Center for Functional Imaging (associated with UCSF)

Biomedical imaging programme at NCI

Duke Center for in vivo microscopy

Journal of Molecular Imaging

MGH Center for Molecular Imaging Research

Ralph Weissleder's lab

The Society for Molecular Imaging

UCLA Crump Institute for Molecular Imaging

Glossary

MAGNETIC RESONANCE IMAGING

(MRI). A powerful diagnostic imaging method that uses radiowaves in the presence of a magnetic field to extract information from certain atomic nuclei (most commonly hydrogen). It is primarily used for producing anatomical images, but also gives information on: the physico-chemical state of tissues, flow, diffusion, motion and, more recently, molecular targets.

X-RAY COMPUTED TOMOGRAPHY

(CT). As generated X-rays pass through different types of tissue, they are deflected or absorbed to different degrees. CT uses X-rays to obtain three-dimensional images by rotating an X-ray source around the subject and measuring the intensity of transmitted X-rays from different angles.

ULTRASOUND IMAGING

Acoustic waves with high frequencies (usually > 10 MHz) are used to generate images based on acoustic echoes.

CHARGE-COUPLED DEVICE

(CCD). Instrument containing semiconductors that are connected so that the output of one serves as the input of the next. Sensitive digital cameras used for image acquisition (for example, in CT, fluorescence and bioluminescence imaging) all use CCD arrays.

'SMART' REPORTER PROBE

Molecular probe that changes its physicochemical properties after target interaction. Occasionally referred to as a sensor, beacon or activatable probe.

SINGLE PHOTON EMISSION TOMOGRAPHY

(SPECT). The rotation of a photon detector array around the body to acquire data from many angles following the injection of a γ-emitting radionuclide (isotope decaying with γ-ray emission of 30–300 KeV energy).

POSITRON EMISSION TOMOGRAPHY

(PET). Tomographic imaging technique detects nuclides as they decay by positron emission. The emitted positrons collide with a free electron, resulting in the conversion of matter to two γ-rays, which emerge in opposite directions.

VOXEL

Also known as 'volume pixel element', it is the smallest distinguishable piece of a three-dimensional image. Clinical magnetic resonance images, for example, often consist of 256 × 256 or 512 × 512 voxel matrices.

SUPERPARAMAGNETIC NANOPARTICLES

Magnetic particles with dimensions in the order of tens of nanometres that are used as reporters in magnetic resonance imaging. Superparamagnetism refers to the fact that the particles do not have magnetic properties outside a magnetic field (unlike ferromagnets).

MR SPECTROSCOPY

(MRS). Nuclear magnetic resonance spectroscopy method used to detect the concentration of specific metabolites in a particular region of a tumour or organ. Individual compounds or ratios might be predictive of response to radiation and chemotherapy.

CYCLOTRON

Device used to produce positron-emitting radionuclides for PET imaging by bombarding non-radioactive target atoms with nuclei (for example, protons or deuterons) that are accelerated to high energies.

LEAD COLLIMATORS

Perforated sheets of lead that are used to focus X-rays or γ-rays. Collimators are crucial elements that determine the sensitivity, resolution and contrast of obtained images.

FLUORESCENCE REFLECTANCE IMAGING

(FRI). Simple method of image acquisition similar to fluorescence microscopy, except that different optics allow image acquisition of whole animals. Mostly suited for surface tumours or surgically exposed tumours.

FLUORESCENCE-MEDIATED TOMOGRAPHY

(FMT). Tomographic reconstruction method developed for in vivo imaging of fluorescent probes. Images of deep structures are mathematically reconstructed by solving diffusion equations, under the assumption that photons have been scattered many times.

PHOTOPROTEIN

Class of proteins that give off light following oxidation or oxidative conversion of a substrate such as luciferin. Usually also requires ATP, oxygen and catalysts.

THREE-DIMENSIONAL MAPPING

Segmenting and volume reconstruction of specific targets, disease processes or organs after image acquisition. Mapping aids in visualizing complex information of tens to hundreds of images.

MULTIMODAL DATA FUSION

Fusion of anatomical (for example, derived from CT or MRI) and physiological or molecular (for example, derived from nuclear or optical imaging) images, into a new synthetic image.

MULTI-WAVELENGTH IMAGING

Fluorescence or absorption imaging at different, non-overlapping wavelengths (also referred to as multicolour imaging). Allows the imaging of multiple targets simultaneously.

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Weissleder, R. Scaling down imaging: molecular mapping of cancer in mice. Nat Rev Cancer 2, 11–18 (2002). https://doi.org/10.1038/nrc701

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