Molecular imaging of stroke
While CT and MR are still the mainstays of detecting ischemic stroke, several SPECT and PET imaging techniques have been developed and are on the way to add comprehensive clinical information in the case of cerebrovascular disease. With this in mind, hybrid imaging such as PET/MR could provide a best-possible map of variables involved in stroke, according to a review published Oct. 9 in the Journal of Nuclear Medicine.
Wolf Dieter Heiss, MD, PhD, from the Max Planck Institute for Neurological Research, Cologne, Germany, wrote the review and listed the most common as well as some emerging radionuclides in this space.
For pathophysiologic changes involved in ischemic stroke, Heiss asserted that PET is especially beneficial, but must be coregistered with either CT or MR, with MR being superior for brain morphology.
“A hybrid system guarantees the same physiologic state for comparative measurements of perfusion by PET and MR imaging,” notes Heiss. “It permits differentiation of the core from the penumbra and can be used to validate a [perfusion-weighted imaging and diffusion-weighted imaging] mismatch. It demonstrates time-dependent growth of infarction and may be used to determine the optimal therapy for a certain time after the stroke.”
SPECT radiopharmaceuticals have been developed for the evaluation of cerebral blood volume, perfusion and hemodynamics. Immediately following stroke, SPECT was found to be 90 percent positive, with sensitivities of 61 percent to 74 percent and specificities of 88 percent to 98 percent.
Commercially available radiopharmaceuticals used for stroke are still lacking in some of the required benchmarks, which include uptake without redistribution in the brain, proper extraction and diffusibility, but they remain clinically valuable due to their approximate adherence to measurements of relative cerebral blood flow.
I-123 isopropyl iodoamphetamine is currently available, but image quality is challenged. Tc-99m agents are helpful due to on-site labeling and Tc-99m hexamethylpropyleneamine oxime (HMPAO) and ethyl cysteinate dimer (ECD) are both rapidly taken up by the brain, but they may underestimate relative cerebral blood flow. Image quality may be better in the latter due to improved stability and brain-to-background activity ratio.
Radionuclides for PET include C-11, O-15 and F-18. Radiotracers using plasma and red cells have been investigated for cerebral blood volume, but some issues with equilibrium and retention regarding the blood-brain barrier have left these hampered. Carbon monoxide labeled C-11 or O-15 inhalation has shown to be useful. Administering a bolus dose of O-15 H2O is the current standard PET method for measuring cerebral blood flow.
“The localization and extent of lesions as a result of defects in blood supply can be assessed by SPECT studies of perfusion and by PET studies of flow or metabolism,” Heiss writes. “Both techniques are more sensitive than CT for detecting both the presence and the extent of infarction.”
As for emerging techniques, F-18 galacto-RGD, a cyclic growth factor receptor peptide, is performing well and showing promise for assessing angiogenesis and revascularization after stroke. This is an area where PET/MR could really shine.
In stroke-related stem cell therapies, grafted stem or progenitor cells are being labeled with iron oxide particles in order to follow the path of migration and propagation at the site of the ischemic lesion. Using MR to scout out cells and PET to assess biologic viability and integration is an up-and-coming technique in the evaluation of stroke treatment.
“With these perspectives, imaging with radioisotopes still has a promising future for research in cerebral ischemia and for clinical management of stroke patients,” concluded Heiss.