In molecular imaging specific processes in living organisms, including gene expresion, protein-protein interaction, dynamic cell tracking throuhout the entire organism
and drug action analysis can be studied. In all cases a specific probe or biomarker has to be found or developed to help image various targets or pathways. Such biomarkers interact chemically with their surroundings and in turn alter the image according to the molecular changes occurring within the area of interest. This ability to image very fine molecular changes opens up an incredible number of exciting possibilities for medical application, including early detection and treatment of diseases as well  as for basic pharmaceutical development such as drug target identification and pre-clinical testing.

The success of molecular imaging over the last years is contributed by
 

• Impressive development of imaging technologies
• Bi- or multicistronic vectors and reporter animals
• Fusion software and digital mouse atlas

Imaging modalities

In the last years different modalities evolved like MRI, PET, SPECT, BLI, FRI, Ultrasound and X-ray CT that can be used for non-invasive molecular imaging of small animals.

On the right of this page different modalities are arranged on a graphic, according to their respective capability of investigating fuctional and anatomical/ morphological features in living organisms.

Magnetic resonance imaging (MRI)
belongs to an own class, because anatomical, physiological and functional imaging is possible, if the magnetic field is high enough. Todays scanners reach magnetic fields of up to 17 Tesla enabeling functional MRI (fMRI).

Nuclear Imaging (NI)
is best choice for functional imaging. Gamma rays emitted by radiotracers such
as 99mTc, 111In, 123I, 201Tl (for SPECT) or emitted after annihilation of positrons from nucleids such as 15O, 18F, 64Cu, 62Cu, 124I, 76Br, 82Rb and 68Ga with nearby electrons (for PET) penetrate tissue without significant absorption and scattering. Other advantages are the fact, that the nuclides are small and will not change properties of targeting
molecule, and sensitivity: a typical PET scanner can detect between 10-11 mol/L to 10-12 mol/L concentrations. Disadvantages are often the short half time of nuclides which have to be produced in a cyclotron.

Optical imaging (OI)
subsummits bioluminescence (BLI) and fluorescence reflectance imaging (FRI), which is also called biofluorescence (BFI) when photoproteins like GFP and their derivatives are used. The major problem of optical imaging is absorption and scattering of
photons in tissue. Since only the photons on the surface can be detected this modality is not quantitative. Anyway, bioluminescence is the most sensitive modality, and most often, also relative data are valuable e. g. tumour growth of orthotopic cancer models.

Anatomical Imaging (AI)
is performed by ultrasound or X-ray CT. Both are not considered as molecular imaging but widely used for fusion with other technologies.

Summary

• There is no all-round imaging method
• Methods are complementary
• Method of choice depends on purpose & availability of probes
• Combination of methods is need to get all required information
  

Animal beds and holders for multimodality imaging

NMR (MRI), PET, CT, SPECT, Ultrasound and Optical Imaging are today's basic technologies applied in molecular imaging research. Each technology has its advantages and provides unique information. Researchers have to do sequential imaging or scanning in different instruments to get the required data.
To benefit from all technologies and to be able to compile and compare the information a mouse has to be kept in the same position during sequential scanning in different instruments. Therefore BERTHOLD TECHNOLOGIES developed different animal beds and holders.

MACU® Multimodal Animal Carrier Unit

For long acquisition times – in MRI up to 4 hours – the animal has to be anaestatized by gas and the temperature controlled.
For this purpose the Medres MACU® - "Multimodal Animal Carrier Unit" - has been developed and adapted to the optical imaging system NightOWL for bioluminescence or bio-fluorescence imaging. With MACU the animal can be imaged with different scanners in one anaesthesia session. Using a rectal temperature probe the unit is heated or cooled with water by a temperature control unit (stability < 0.2 °C). Anaesthesia is supplied by a mask in combination with the bite bar. Surplus gas is removed with a vacuum line. ECG is none invasivly done by forepaw electrodes. For NMR investigation a 30 mm Helmholtz detector can be added to the setup and removed without interfering with the animal. The mobile operation and transportation unit supports all MACU features body temperature, ECG, respiration, etc.

Since the NightOWL camera can be moved vertically inside the light-tight cabinet, the image size can be adjusted to the respective image taken by MRI or PET instruments.
MACU option for NightOWL consists of MACU carrier, flange and MACU plate carrier. To adapt the MACU flange, the NightOWL has to be equipped with the flange option.
The MACU flange´s diameter is 14 cm, so the carrier unit for a 12 cm MRI-bore fits easily. The MACU flange is light-tight, even though transparent tubings for water and gas are used.

On the MACU plate a guide rail is integrated for easy mounting and exact positioning of MACU. A stopper on the plate avoids crashes of the camera with MACU in case of accidential movement.