Feature article

PET/MR Imaging: What is its Potential for Assessing Cognitive Impairment After Stroke?

More than 795,000 people in the United States suffer a stroke every year, according to the Centers for Disease Control and Prevention. About 610,000 of these are first strokes, while 1 in 4 are repeat strokes. Stroke is a leading cause of significant, long-term disability, with more than half of stroke survivors who are 65 years or older suffering a reduction in mobility after their stroke.1

As many as 55 percent of stroke patients may develop post-stroke dementia, which is defined as “the presence of dementia identified at three months after an acute, either recurrent or first-ever, stroke." Other patients may have cognitive impairment that does not rise to the level of dementia, but places them at increased risk of further cognitive decline.2

A study in 2015 estimated that up to 72 percent of patients have some form of cognitive impairment after a stroke.3 Another study that looked at 409 patients in Finland found that 83 percent of patients showed impairment in at least one cognitive domain, with 50 percent impaired in multiple domains of cognitive functioning. Even when patients had excellent clinical recovery, the authors found that 71 percent of patients were cognitively impaired. Even mild cognitive deficits related to stroke can negatively affect quality of life, occupational functioning, and independent functioning.4

Researchers do not yet fully understand the mechanisms that underlie post-stroke cognitive impairment. There is also evidence that suggests that post-stroke cognitive impairment may lead not only to vascular cognitive impairment (VCI), formerly called vascular dementia, but that it may also contribute to the pathogenesis of Alzheimer’s disease.5

Current applications of PET/MR in neurofunction

Simultaneous magnetic resonance imaging (MRI) and positron emission tomography (PET) scanning is a fairly recent, and major, development in imaging technology. Achieving integration between MRI and PET systems has proven technologically challenging. But there are synergies that can be achieved with this type of simultaneous PET/MR imaging, particularly in neuroimaging and cognitive neuroscience. MRI has very high sensitivity, and thus is able to image very small changes in both brain structure and function. PET’s strength is in its ability to image numerous molecular targets such as oxygen usage, glucose metabolism, and neurotransmitter distribution in the brain.6

MRI is considered the standard tool for brain imaging in neurodegenerative diseases because of the high spatial resolution and high soft tissue contrast that it yields. MRI is often used to diagnose suspected neurodegenerative disorders, allowing the exclusion of other causes such as brain tumors, inflammatory changes, or vascular disease. And in some neurodegenerative disorders, a particular pattern of brain atrophy may lead to a diagnosis.7

PET imaging has been used in neurodegenerative disease as well, because of its high sensitivity to specific molecular targets. [18F]FDG, the most commonly used PET tracer in imaging neurodegenerative diseases, “represents a universal marker of neuronal and synaptic integrity with relatively disease-specific uptake reduction patterns,” according to a review of the use of hybrid PET/MR in dementia and neurodegenerative diseases. The tracer will show different patterns for Alzheimer’s versus frontotemporal lobar degeneration, or for primary Parkinson’s disease and atypical parkinsonian syndromes. [18F]FDG is a useful tracer for Huntington’s disease, amyotrophic lateral sclerosis, and Creutzfeldt-Jakob disease.

The first series of hybrid PET/MR imaging was published in 2013, using[18F]FDG as the PET tracer, on patients with Alzheimer’s, dementia with Lewy bodies, and frontotemporal lobe degeneration.8 While some additional studies have been done using PET/MRI in dementia and parkinsonian syndromes, there has been little done to look at this imaging system in other neurodegenerative diseases like Huntington’s disease, ALS, or prion diseases.9

Barthel et al., writing in Seminars in Nuclear Medicine, feel there is great potential for the application of PET/MRI “by delivering relevant biomarker information in a one-stop-shop fasion, to significantly improve and simplify early and differential diagnosis” of neurodegenerative diseases.10

How might PET/MR help determine cognitive function in patients who have had a stroke?

MRI is used often in the evaluation and differential diagnosis of stroke. It is able to image the occlusion or rupture of blood vessels in the brain and allow the clinician to determine many parameters: size, age, position, and even the reversibility of the stroke. PET is less often used in the acute stroke setting, but its addition to MRI systems can add important information in determining cognitive functioning and differential diagnosis.

In 2015, Werner et al. published a case series utilizing hybrid PET/MRI and [15O]H2O as a tracer with ten patients who had symptoms of stroke with the goal of identifying critically hypoperfused brain tissue. While the study had limitations, the authors conclude that hybrid PET/MR is a “promising tool for validating MR-based stroke imaging concepts.”11

While this study looked at patients within the first hours after stroke, there is little published research so far that applies the principles of PET/MR imaging to cognitive impairment after stroke, which can develop in the weeks and months following the event. However, while post-stroke cognitive impairment is often thought of as separate from mild cognitive impairment, the “borders between degenerative and vascular dementias are not sharp and mixed pathologies may be found in 20% of patients with cognitive impairment,” write Brainin et al. Thus, the techniques that apply to imaging in other neurodegenerative disorders may be of use in stroke patients with cognitive impairment as well.12

For example, MRI can be used to show the size of the infarct and location of the vascular lesion, as well as involvement of any fiber tracts between functional networks. Because vascular (including post-stroke) dementia causes changes in the cerebral blood flow and glucose metabolism, FDG-PET is useful to help differentially diagnose types of dementia—distinguishing Alzheimer’s disease from vascular dementia, for example.13 Combining the two technologies to take simultaneous PET/MR images may yield the synergistic benefit of a complementary combination—providing new levels of information greater than either can provide alone.

References

  1. Stroke Facts. Centers for Disease Control and Prevention. https://www.cdc.gov/stroke/facts.htm Last accessed December 23, 2018.
  2. Cognitive Impairment After Stroke. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4627858/ Last accessed December 23, 2018.
  3. Cognitive Impairment After Stroke. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4627858/ Last accessed December 23, 2018.
  4. Post-Stroke Cognitive Impairment Is Common Even After Successful Clinical Recovery. European Journal of Neurology. https://onlinelibrary.wiley.com/doi/full/10.1111/ene.12743 Last accessed December 23, 2018.
  5. Post-Stroke Cognitive Impairment: Epidemiology, Mechanisms and Management. Annals of Translational Medicine. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4200648/ Last accessed December 23, 2018.
  6. From Simultaneous to Synergistic MR-PET Brain Imaging: A Review of Hybrid MR-PET Imaging Methodologies. Human Brain Mapping. https://onlinelibrary.wiley.com/journal/10970193 Last accessed December 23, 2018.
  7. PET/MR in Dementia and Other Neurodegenerative Diseases. Seminars in Nuclear Medicine. https://www.sciencedirect.com/science/article/pii/S0001299814001469 Last accessed December 23, 2018.
  8. Clinical Applications of Hybrid PET/MRI in Neuroimaging. Clinical Nuclear Medicine. https://journals.lww.com/nuclearmed/Abstract/2013/01000/Clinical_Applications_of_Hybrid_PET_MRI_in.25.aspx Last accessed December 23, 2018.
  9. PET/MR in Dementia and Other Neurodegenerative Diseases. Seminars in Nuclear Medicine. https://www.sciencedirect.com/science/article/pii/S0001299814001469 Last accessed December 23, 2018.
  10. PET/MR in Dementia and Other Neurodegenerative Diseases. Seminars in Nuclear Medicine. https://www.sciencedirect.com/science/article/pii/S0001299814001469 Last accessed December 23, 2018.
  11. Current Status and Future Role of Brain PET/MRI in Clinical and Research Settings. European Journal of Nuclear Medicine and Molecular Imaging. https://link.springer.com/article/10.1007/s00259-014-2970-9 Last accessed December 23, 2018.
  12. Post-stroke Cognitive Decline: An Update and Perspectives for Clinical Research. European Journal of Neurology. https://onlinelibrary.wiley.com/doi/full/10.1111/ene.12626 Last accessed December 23, 2018.
  13. Post-stroke Cognitive Decline: An Update and Perspectives for Clinical Research. European Journal of Neurology. https://onlinelibrary.wiley.com/doi/full/10.1111/ene.12626 Last accessed December 23, 2018.