Nov 17, 2010
Optical-PET study bags PMB citations prize
A research paper on tomographic bioluminescence imaging has won its authors the 2010 Physics in Medicine & Biology (PMB) citations prize – an annual award for the PMB research paper that received the most citations in the preceding five years (according to ISI).
The winning paper – Tomographic bioluminescence imaging by use of a combined optical-PET (OPET) system: a computer simulation feasibility study – was authored by George Alexandrakis, now at the University of Texas at Arlington, Fernando Rannou from Universidad de Santiago in Chile, and Arion Chatziioannou from the University of California, Los Angeles (Phys. Med. Biol. 50 4225).
The study describes a combined optical and PET (OPET) small-animal imaging system. The authors investigated the system's potential by simulating the image formation process using a micro-MRI-based virtual mouse phantom. The phantom's internal organs were assigned appropriate optical properties at wavelengths spanning the emission spectrum of the firefly luciferase bioluminescence probe.
The researchers then simulated OPET measurements for single-point, two-point and distributed bioluminescence sources located in different organs within the mouse. This revealed that spectrally resolved measurements were necessary for tomographic imaging. Simulated measurements at a single wavelength were unable to achieve three-dimensional source localization. OPET measurements at two wavelengths, however, could produce tomographic images, while additional wavelengths further improved source localization.
The simulations also demonstrated that the true location of emission sources relied on knowledge of the mouse background optical properties. The assumption of a homogeneous optical background led to inaccurate source localization in the reconstructed images.
"I think that the novelty [of this work] came from the combination of two different imaging techniques, bioluminescence tomography and PET, in a single setup," Alexandrakis told medicalphysicsweb. "The concept was that the PET detectors also capture the bioluminescence signal so that images from both modalities are intrinsically co-registered in space."
This feature allows PET imaging to be employed to validate or augment the capacity of bioluminescence tomography for quantitative imaging. It also enables simultaneous acquisition of the different types of physiological information offered by PET tracers and bioluminescence reporters.
In the five years since the PMB paper was published, the imaging side of this field has become more computationally intensive, with researchers working to reconstruct more accurate and sharper images. Alexandrakis points out, however, that the computational resources required to implement such improvements remain significant, limiting the widespread use of such methods.
Most efforts are now focused on expanding the range of biological applications for tomographic bioluminescence imaging. "Current directions include following the kinetics of transplanted stem cells, the evolution of infectious and neurodegenerative diseases, and tumour response to cancer treatments in small animal models, to name a few," said Alexandrakis.
On the biochemistry side, he noted, the "holy grail" remains the creation of enzyme mutants that generate bioluminescence emission shifted towards red and near-infrared wavelengths, which would enable deeper and more sensitive tissue imaging. "This goal remains elusive to date."
The PMB citations prize is marked with the presentation of the Rotblat medal. The medal, named in honour of Prof. Sir Joseph Rotblat (PMB's second and longest serving editor), was awarded to the authors at the recent IEEE Medical Imaging Conference in Knoxville, TN.
"I am of course very happy to receive this prize," said Alexandrakis. "It was a big surprise – the announcement came out of the blue. I had noticed that the article was being cited, as I was following up on the literature, but I had not realized that it was that popular. I am very grateful for having the luck to cross paths with my then postdoctoral advisor, Dr Chatziioannou, as well as Dr Rannou, who is now a professor in Chile. They are intelligent and kind colleagues who made this work possible."
• The winner of the 2010 Physics in Medicine & Biology (PMB) citations prize is: Tomographic bioluminescence imaging by use of a combined optical-PET (OPET) system: a computer simulation feasibility study Phys. Med. Biol. 50 4225.
About the author
Tami Freeman is editor of medicalphysicsweb.