An arterial spin labeling investigation of cerebral blood flow deficits in chronic stroke survivors

Abstract

Although the acute stroke literature indicates that cerebral blood flow (CBF) may commonly be disordered in stroke survivors, limited research has investigated whether CBF remains aberrant in the chronic phase of stroke. A directed study of CBF in stroke is needed because reduced CBF (hypoperfusion) may occur in neural regions that appear anatomically intact and may impact cognitive functioning in stroke survivors. Hypoperfusion in neurologically-involved individuals may also affect BOLD signal in FMRI studies, complicating its interpretation with this population. The current study measured CBF in three chronic stroke survivors with ischemic infarcts (greater than 1 year post-stroke) to localize regions of hypoperfusion, and most critically, examine the CBF inflow curve using a methodology that has never, to our knowledge, been reported in the chronic stroke literature. CBF data acquired with a Pulsed Arterial Spin Labeling (PASL) flow-sensitive alternating inversion recovery (FAIR) technique indicated both delayed CBF inflow curve and hypoperfusion in the stroke survivors as compared to younger and elderly control participants. Among the stroke survivors, we observed regional hypoperfusion in apparently anatomically intact neural regions that are involved in cognitive functioning. These results may have profound implications for the study of behavioral deficits in chronic stroke, and particularly for studies using neuroimaging methods that rely on CBF to draw conclusions about underlying neural activity.

Figure 1

Illustration of a pulsed arterial spin labeling (PASL) perfusion imaging sequence. A radiofrequency pulse inverts the magnetization of inflowing arterial blood (a). This tagged blood flows into the imaging slice over a period of seconds, and an image is acquired. To serve as a control (b), an image is then acquired in the same location, without the use of a tagging pulse to invert the magnetization of blood. Subtraction of control images from tagged images results in an image of only the inflowing tagged blood to the region of interest. Perfusion transit delays (signified by the upward arrows) indicate the amount of time that elapses between tagging inflowing blood and acquiring an image (Illustration courtesy of Patrick J. Lynch, medical illustrator; C. Carl Jaffe, MD, cardiologist).

Figure 2

Neuroanatomical and Cerebral Blood Flow (CBF) images for each stroke survivor: Column A shows images from participant LHD1, Column B shows images from LHD2, and Column C shows images from LHD3. The top row shows a time-of-flight angiogram for each participant, with occlusion of the Middle Cerebral Artery territory indicated by the arrow in each participant's scan. The second and third rows show high-resolution (1mm isotropic voxels) Spoiled Gradient Recalled (SPGR) images from sagittal and axial viewpoints, respectively. Sagittal views show each participant's left hemisphere as affected by stroke. The bottom row shows whole-brain CBF for each participant (scale shown at bottom).

Figure 3

An example of the a) left and b) right hemisphere penumbra mask regions, illustrated with participant LHD2's data. Left hemisphere penumbra regions were defined by outlining the borders of each stroke survivor's lesion and creating a 2 voxel border around the lesion. Right hemisphere mask regions were created by copying the mask from the left hemisphere and transposing it into the homologous region of the right hemisphere. Penumbra masks were equivalent across participants for extent from the lesion (6.88 mm in the right-left direction, 6.88 mm in the anterior posterior direction, and 13.88 mm in the inferior-superior direction) and were equivalent within participants across hemispheres for anatomical location.