Rationale for the Combination of Nuclear Medicine with Magnetic Resonance for Pre-clinical Imaging

Abstract

Multi-modality combinations of SPECT/CT and PET/CT have proven to be highly successful in the clinic and small animal SPECT/CT and PET/CT are becoming the norm in the research and drug development setting. However, the use of ionizing radiation from a high-resolution CT scanner is undesirable in any setting and particularly in small animal imaging (SAI), in laboratory experiments where it can result in radiation doses of sufficient magnitude that the experimental results can be influenced by the organism's response to radiation. The alternative use of magnetic resonance (MR) would offer a high-resolution, non-ionizing method for anatomical imaging of laboratory animals. MR brings considerably more than its 3D anatomical capability, especially regarding the imaging of laboratory animals. Dynamic MR imaging techniques can facilitate studies of perfusion, oxygenation, and diffusion amongst others. Further, MR spectroscopy can provide images that can be related to the concentration of endogenous molecules in vivo. MR imaging of injected contrast agents extends MR into the domain of molecular imaging. In combination with nuclear medicine (NM) SPECT and PET modalities in small animal imaging, MR would facilitate studies of dynamic processes such as biodistribution, pharmacokinetics, and pharmacodynamics. However, the detectors for nearly all PET and SPECT systems are still based on vacuum tube technology, namely: photomultiplier tubes (PMT's) in which the signal is generated by transporting electrons over a substantial distance within an evacuated glass tube, making them inoperable in even small magnetic fields. Thus the combination of SPECT or PET with MR has not been practical until the recent availability of semiconductor detectors such as silicon avalanche photodiodes (APD's) for PET and CdZnTe (CZT) detectors for SPECT coupled with the availability of high-density low noise ASIC electronics to read out the semiconductor detectors. The strong advantage of these technologies over PMT's is their insensitivity to magnetic fields which makes their use in co-axial multi-modality nuclear medicine/magnetic resonance instrumentation possible.

SPECT Low-Field MRI System for Small-Animal Imaging

“…In our experiments, an isotropic spatial resolution of 1 mm was obtained by pinhole SPECT with a reconstructed voxel of 0.47 · 0.47 · 0.47 mm 3 (14,23). It is also obvious that isotropic voxel MR images are recommended for optimal coregistration with SPECT.…”

“…As physiologic movements of the animal and tissues due to circulation, respiration, and fluid flow cannot be systematically controlled, it also seems unrealistic to aim for MR spatial in-plane resolution below 0.2 · 0.2 mm 2 (25,26). Compared with high and very high magnetic fields, dealing with the relative voxel sizes achieved by each of the combined technologies also does not make sense to merge SPECT data, whose spatial resolutions are on the order of 1 mm 3 , with MR spatial resolutions of 0.001 mm 3 . Of course, the major, but almost only, disadvantage of a low magnetic field compared with a high field (proton spectroscopic information notwithstanding) is the reduction in the signal-to-noise (S/N) ratio.…”

“…Images were reconstructed with an inhouse efficient algebraic cone beam reconstruction method based on an algebraic reconstruction technique (ART) algorithm that takes into account the variation of the radius of rotation and is able to achieve an isotropic 1 · 1 · 1 mm 3 spatial resolution (efficient algebraic reconstruction [EAR] method (14)). The size of the isotropic reconstructed voxel was 0.47 · 0.47 · 0.47 mm 3 . The cost of the complete pinhole SPECT apparatus was around $50,000.…”

“…Therefore, localization of regions with increased uptake of radiotracer is greatly facilitated when using coregistration of SPECT with anatomic images of the same animal, from CT or MRI. Over the last few years, SPECT/ CT dual modality has been widely proposed by manufacturers but MRI presents specific advantages compared with CT, including lack of ionizing radiation, high soft-tissue contrast, and sensitivity to tissue alterations evidenced by specific imaging sequences (2,3). Yet, compared with CT, the use of MRI for coregistration of both functional and structural information has, to our knowledge, essentially served to demonstrate the potential interest of using coregistration of images after data acquisition in separate nuclear and MR rooms.…”

“…In addition, separate dual-modality scans (followed by image fusion) are also potential sources of misalignment of images due to uncontrolled movements and displacements of tissues and organs. Moreover, multiple anesthesia sessions are needed when SPECT and MRI devices are located in separate places, involving the risk of different biologic responses to anesthesia (3). After early rodent MRI works done on clinical low-field systems operating at 0.35 T (8), smallanimal MRI is now performed exclusively at very high magnetic fields operating at values up to 14 T, in a desire to achieve high anatomic resolution benefiting from a higher signal-to-noise ratio but leading to field susceptibility artifacts and preventing close proximity of the SPECT scanner (2,9).…”