PET/MRI: Where We Are, Where Were Going
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The promise of PET /MRI imaging comes from the metabolic functionalinformation that PET provides and the detailed anatomicmorphology of MRI —without the radiation dose of CT. PET/MRI ’s simultaneous imaging also ensures more exact scanning. Because of the excellent soft tissue contrast, the morphological information provided by MRI is superior to CT for neurological studies, providing the anatomical context for analyzing the metabolic PET data.
The uniting of PET and MRI allows researchers to acquire data about brain physiology and biochemistry, which provides more definitive determination of cognitive impairment. The hybrid uses a minimally invasive method yielding quantitative, reliable information that can be used to treat and manage neurodegenerative diseases such as Alzheimer’s and Parkinson’s. Some researchers say it could help physicians locate salvageable brain tissue in stroke patients.
PET/MRI data also could be used to treat pancreatic and brain tumors, and researchers say the information is also useful in cardiovascular applications to study heart function.
PET/MRI development also has its challenges. Current PET instrumentation must be re-engineered with solid-state detectors because the MRI magnet affects the photomultiplier tubes essential for CT . Also, the MR image cannot be converted into an attenuation map for PET as easily as with CT. Yet, engineers and researchers are confident the challenges will be overcome.
Progress in preclinical
Simon R. Cherry, PhD, a professor in the Department of Biomedica lEngineering and director of the Center for Molecular and Genomic Imaging at the University of California, Davis, is a pioneer in microPET and microPET/MR technology. He is using the technology to image the brains of mice, rats and monkeys seeking information to treat Alzheimer’s disease in humans.Cherry has developed a preclinical microPET prototype system integrated into a standard Bruker 7T BioSpin MR unit designedfor animal imaging with a spatial resolution of 1.2 mm, axial field-of-view of 12 mm and transaxial field-of-view of 35 mm.
Technological developments in the combined modalities now allow researchers to correct for physiological motion artifacts, providing the ability to monitor the heart and respiration. “You can image the beating heart, you can look at how the wall is moving, and you can actually estimate the stress and strain on the heart so you can combine all this information and really learn a lot about what’s going on,” Cherry explains.
He also predicts PET/MRI will someday be useful in studying stem cell therapies in humans. “We’re going to need [imaging] techniques that will tell us what’s happening to these cells after we put them in the body, and the ability to monitor these stem cells that we put in—what happens to them and whether they proliferate, how they differentiate,” he says.
Cherry just received a grant from the U.S. National Institutes of Health to build the next-generation PET insert for his micro-PET/MRI system which will provide higher spatial resolution and higher sensitivity.
About a quarter turn around the globe from Cherry, Professor Bernd Pichler, PhD, head of the Laboratory for Preclinical Imaging and Imaging Technology at the University Hospital in Tübingen, Germany, is developing microPET/MRI as well. Pichler is using a different detector approach for the two systems he is developing—one preclinical and one clinical—both focusing on brain imaging.
“We can get multi-functional information from PET/MRI along with high-resolution, which allows us to study tumor oncology like perfusion and tracer uptake, hypoxia, proliferation, glucose metabolism and do a lot of studies in brain imaging like perfusion and tracer uptake for studying Alzheimer’s disease,” Pichler says.
The preclinical small animal research is focused on oncology applications particular to pancreatic and brain tumors, neurologic imaging of Alzheimer’s and Parkinson’s diseases and the dopaminergic system as well as applications in cardiology using simultaneously acquired PET/MRI infarcted mouse hearts. The preclinical scanner uses a PET insert that his team built which is integrated with a 7T MRI from Bruker.
Pichler’s clinical system is used primarily to study the human brain, focusing on neuro-oncology applications to measure PET tracer uptake at the same time with MRI information such as contrast agent enhancement or proton spectroscopy.
The PET scanner is integrated into a standard Siemens 3TMagnetom Trio MRI unit. The PET/MRI system has a spatia lresolution of ~3 mm, axial field-of-view of 19 cm and transaxial field-of-view of 30 cm.
Pichler says there are several advantages of the combined systems: better quantification of the PET signal; complementary MRI information (fMRI perfusion, blood oxygenation and highanatomic resolution) with molecular PET information (tracer uptake for proliferation and glucose metabolism); and simultaneous measurement of PET/MRI data to allow for compensation of motion artifacts, he explains.
Back in the U.S., clinical PET/MRI work is underway in Boston. Ciprian Catana, MD, PhD, a former student of Cherry’s who is now an instructor in radiology at Harvard Medical School and an assistant in neuroscience at Massachusetts General Hospital’s Department of Radiology, is using the only U.S.-based clinical PET/MRI prototype scanner (Siemens). Catana—working witha group led by A. Gregory Sorensen, MD , the associate director of the Martinos Center for Biomedical Imaging, co-director of the Cancer Imaging Program at the Dana Farber/Harvard Cancer Center, and director of the Biomedical Imaging Core of the MGH General Clinical Research Center—has completed about 10 human brain tumor studies during the last year.
The PET/MRI scanner is integrated into a standard 3T Magnetom Trio MRI unit. Using advanced MRI techniques has offered additional information about brain physiology including cerebral blood flow and water diffusivity.
PET and MRI provide complementary information that allows more precise probing of disease pathophysiology and assessment of drug response, Catana says. On one hand, understanding the mechanism of action of different therapeutic agents would allow a better selection of those patients who are likely to benefit from a particular therapy. On the other hand, a more reliable method to evaluate the therapeutic response would reduce the number of subjects required to answer a specific question in a clinical trial.
“All this wealth of information is obtained without additional radiation exposure as is the case with CT,” Catana notes.
Beyond the potential for PET/MRI, future success in human scanning depends on whether its clinical applications add clinical, speed and financial benefits over existing technology, Cherrynotes. “If it turns out we can’t find clinical applications where PET/MRI adds some significant value at a price insurers are willing to pay, then this technology will fall flat on its face,” he observes. “The companies [developing systems] will pull out because they won’t be able to make money, and it will remain just a research tool.”
But now that Siemens and Philips are both developing systems designed to use the hybrid modality for expanded human scanning, the prospects look promising, Cherry says.
“I think in the next year or two we’ll see commercial availability of whole-body PET/MRI for humans and microPET/MRI for animals,” Cherry predicts.
It also is worth pointing out that while MR imaging is currently used in only a miniscule percentage of oncology scans compared with CT or PET/CT —the use of PET coupled with MRI has the potential to widen greatly. And while it’s too early to speculate on PET/MRI ’s long-term patient care benefits, preclinical PET/MRI is excelling in all uses. It is, thus, moving biological research forward as well as technology development—and in the future this will likely translate into better instrumentation.