Evaluation of PCASL Imaging and T2* Mapping for the Assessment of Cerebrovascular Reactivity in the Hippocampus
Xiufeng Li1, Nicholas Evanoff2, Lynn E. Eberly 3, Anne M. Murray4, Gregory J. Metzger1, and Donald R. Dengel2

1Center for Magnetic Resonance Research, School of Medicine, University of Minnesota, Minneapolis, MN, United States, 2Laboratory of Integrative Human Physiology, School of Kinesiology, University of Minnesota, Minneapolis, MN, United States, 3Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, MN, United States, 4Berman Center for Clinical Research, Hennepin County Medical Center, Minneapolis, MN, United States

Synopsis

The hippocampus is significantly affected in cognitive impairment, including Alzheimer’s disease. Cerebrovascular endothelial dysfunction (CeV-ED) plays an essential role in the initiation and progression of cerebrovascular disease (CeV-D) and cognitive decline. CeV-ED can be assessed with the evaluation of cerebrovascular reactivity (CeV-R) by performing MRI studies with a respiratory challenge, such as the manipulation of end-tidal partial pressure of CO2 (PetCO2) and O2 (PetO2). In the presented studies, ASL imaging and T2* mapping were evaluated for the assessment of the CeV-R in the hippocampus to determine the benefits and disadvantages of each imaging method and to facilitate the imaging method selection for future application studies.

PURPOSE

The hippocampus is significantly affected in cognitive impairment, including Alzheimer’s disease 1-5. Cerebrovascular endothelial dysfunction (CeV-ED) plays an essential role in the initiation and progression of cerebrovascular disease (CeV-D) and cognitive decline 6. CeV-ED can be assessed with the evaluation of cerebrovascular reactivity (CeV-R) by performing blood oxygen level dependent (BOLD) 7, arterial spin labeling (ASL) imaging 8 or T2* mapping 9 with a respiratory challenge, such as the manipulation of end-tidal partial pressure of CO2 (PetCO2) and O2 (PetO2). In contrast to BOLD imaging, ASL imaging with a respiratory challenge can simultaneously provide quantitative baseline CBF and the assessment of the CeV-R, but requires long acquisition time due to its intrinsic low perfusion signal-to-noise ratio (SNR). Compared to ASL imaging, T2* mapping with a respiratory challenge can also provide the estimates of the CeV-R, but with higher resolution and shorter acquisition time. In this study, ASL imaging and T2* mapping were evaluated for the assessment of the CeV-R in the hippocampus to facilitate the imaging method selection for future application studies.

METHODS

Studies were performed with five healthy volunteers (age: 53 ± 18 years) on a Siemens 3T MRI scanner using a 32-channel head coil under an IRB approved protocol with informed written consent. Precise and repeatable control of PetCO2 is crucial to avoid the confounding effects of ventilatory response and minimize inter-subject and inter-session variability for CeV-R measurements 10. A prospective PetCO2 targeting approach was employed to produce PetCO2 values to within ±1 mmHg and constrained PetO2 (< 10 mmHg) 11. PetCO2 and PetO2 were independently targeted via the administration of gases containing mixtures of O2, CO2, and N2 to a sequential gas-delivery breathing circuit by a computer-controlled gas blender (RespirAct, Thornhill Inc.) 12. The targeted PetCO2 challenge was achieved by increasing the level of PetCO2 10 mmHg above each subject’s baseline while PetO2 was held constant during targeted PetCO2 challenge (Figure 1). The major parameters for pseudo-continuous arterial spin labeling (PCASL) imaging are: resolution = 3.0 x 3.0 x 5.0 mm3, labeling duration/post-bolus delay = 1.5/1.6 s, and total number of measurements = 372. T2* mapping was performed with one 3-minute hypercapnia acquisition preceded and followed by 3-minute normocapnia acquisitions, and used a 3D multi-echo gradient recalled echo (GRE) sequence with the following major parameters: resolution = 1.6 x 1.6 x 3.6 mm3, and TE = {4, 10, 16, 22, 28, 34} ms. To avoid potential confounding effects from the transition of respiratory conditions (Figure 3), T2* mapping was performed 20 s after the change of respiratory condition and lasted about 2 and a half minutes.

Similar image processing methods, such as the segmentation of the hippocampus and its co-registration to parametric maps, were applied to estimate hippocampal CBF and T2* values 5,13. The CeV-R was evaluated as the PetCO2-induced percent changes of hippocampal CBF and T2* value. For hippocampal CBF estimation, three pairs of label and control images (about 20 s) following the change of respiratory condition were excluded. To minimize the effects of hyper-intensive T2* values from the nearby CSF and susceptibility-associated signal loss, trimmed mean values within hippocampal ROI were used for the estimation of hippocampal T2* by excluding the 5% of voxels with the lowest values and 5% voxels with highest values.

RESULTS AND DISCUSSION

Both PCASL imaging and T2* mapping exhibit a significant cerebrovascular response to the targeted PetCO2, and the response by PCASL imaging is significantly higher than that by T2* mapping (Figures 2-4). The percent changes of hippocampal CBFs tend to correlate with the percent changes of hippocampal T2* values (Figure 5). Compared to PCASL imaging, T2* mapping suffers from severe susceptibility effects in the middle-inferior brain regions (Figure 1) and the hyper-intensive T2* signals from the CSF, affecting the reliability of hippocampal T2* estimation and resulting in larger inter-subject variability than PCASL imaging: 21% coefficient of variation for T2* mapping and 16% coefficient variation for PCASL imaging. Decreasing the applied longest TE for T2* mapping can reduce susceptibility effects, but may affect the accuracy of T2* estimation. To reduce the partial volume effects on hippocampal CBF estimation, PCASL imaging should be applied with higher imaging resolution for future studies, which can be facilitated by employing an advanced imaging method, such as multi-band EPI PCASL imaging 14.

CONCLUSION

The CeV-R in the hippocampus has been successfully assessed by using both T2* mapping and PCASL imaging. Although compared to T2* mapping, PCASL imaging appears to be a more attractive approach, higher imaging resolution is needed to reduce the partial volume effects on hippocampal CBF estimation.

Acknowledgements

P41 EB015894, P30 NS076408, Human Connectome Project (1U54 MH091657) and UL1TR000114. This research work is also supported by the University of Minnesota Foundation. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

References

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Figures

Figure 1. Illustration of PetCO2 targeting paradigm for the evaluation of cerebrovascular reactivity (CeVR) using PCASL imaging. ΔPetCO2 is the relative changes of end tidal partial pressure of CO2.

Figure 2. One subject’s T2* maps from 3D multi-echo GRE imaging and CBF maps from PCASL perfusion imaging under normocapnic and hypercapnic respiratory conditions.

Figure 3. CBF time course in the hippocampus from an average of the two periods in a given gas challenge acquisition. Green and red blocks represent normocapnic and hypercapnic respiratory conditions, respectively, and vertical red lines indicate 20 s after the changes of respiratory conditions.

Figure 4. Hippocampal CBF (left) and T2* (right) measurements under normocapnic (green) and hypercapnic (red) respiratory conditions. Error bars represent one standard error of the mean.

Figure 5. Scatter plots for relative percent changes of hippocampal CBF and T2* between normocapnic and hypercapnic respiratory conditions.



Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)
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