Shruti Agarwal1, Jun Hua2,3, Haris I. Sair1, Sachin K. Gujar1, Hanzhang Lu2,3, and Jay J. Pillai1,4
1Division of Neuroradiology, Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, United States, 2Division of MR Research, Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, United States, 3F. M. Kirby Research Center For Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, United States, 4Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD, United States
Synopsis
Cerebrovascular reactivity (CVR) provides clinical insight into vascular
health and is useful for identifying cortical regions affected by neurovascular
uncoupling (NVU). BOLD imaging using breath-hold (BH) tasks can be effectively
used for CVR mapping. At 7T, spatial specificity can be improved relative to
standard 3T imaging, but optimization of CVR maps is often problematic. We
propose temporal correction of the theoretical hemodynamic response function
(HRF) to account for subject-wise temporal adjustment of the average
respiration-induced hemodynamic response to a BH task to optimize 7T BH CVR
maps in cases of poor patient task compliance.
Purpose
Cerebrovascular reactivity (CVR) can
be useful for identification of cortical regions affected by neurovascular
uncoupling (NVU).1
CVR is defined as the change in cerebral blood flow (CBF) per unit change in a
vasoactive stimulus. CVR mapping can be accomplished using BOLD imaging with a
breath hold (BH) task. BOLD image contrast mechanisms differ at conventional (≤
3T) and ultrahigh (≥ 7T) fields. At 7T,
BOLD signal more closely reflects the concentration of deoxyhemoglobin in
capillaries rather than in larger veins (unlike at 3T), and therefore, spatial
specificity is improved since cortical neuronal activity is more closely linked
to blood flow changes in the microvasculature than in larger vessels.2,3 In this study,
we propose a temporal correction of the theoretical hemodynamic response
function (HRF) for optimization of 7T BH CVR maps in light of subject-wise
temporal variability of the average respiration-induced hemodynamic response to
a BH task. Methods
Fourteen patients with de novo primary
brain tumor referred for routine 3T clinical presurgical fMRI mapping at our
institution also underwent a ultra-high field (7T)
fMRI study on the same day or at most within three
weeks of the clinical fMRI scan and prior to surgical resection or initiation
of chemoradiation therapy. This study was approved by our Institutional Review
Board. Imaging was performed on a 3.0 T Siemens Trio MRI with a
12-channel head matrix coil using a 3D T1 MPRAGE for structural imaging and
multiple 2D GE-EPI T2* weighted BOLD sequences for task functional imaging. 7T
scanning was performed using research sequences on a 7.0T Philips MRI system
with a 32-channel head matrix coil using a 3D T1 3D MPRAGE imaging sequence for
structural imaging and multiple 2D fast echo planar imaging T2*-weighted BOLD sequences
for functional imaging. The breath hold (BH) task includes normal breathing
period of 40 seconds followed by a 4 second block of slow controlled inspiration
that immediately preceded each 16-second BH period.4
This cycle was repeated four times and at the end of the last BH period an
additional normal breathing period of 20 seconds was added. SPM12 software was
used for preprocessing of BH data (slice timing correction, realignment,
normalization to MNI space at 2mm voxel resolution, and spatially smoothing
using a 6 mm FWHM Gaussian kernel). Z-score maps for BH tasks were obtained
using general linear model (GLM) analysis using a theoretical HRF5 reflecting
hypercapnia vs. baseline. Cortical regions in the contralesional hemisphere
were automatically parcellated using an Automated Anatomical Labeling (AAL)
template6 for each patient. The average time course (TC) of
contralesional voxels in the 7T BH CVR map was obtained (see plot in Fig 1). Goodness
of fit between peaks in the TC plot and those in the theoretical HRF (see black
dotted curve in the plot) using root mean square error (RMSE) was calculated
for various time shifts of the HRF to obtain the optimal time shift where the
best fit occurs according to least RMSE. This time shift was considered as the
optimal temporal correction for the HRF. GLM analysis was then performed using
the temporally corrected HRF. The obtained corrected 7T BH CVR maps were then
compared with 3T BH CVR maps. Four 3T cases
and one 7T case were discarded due to motion degraded BH data. Of the remaining
nine cases, six cases (67%) demonstrated substantial improvement in the BH CVR
map quality following application of this HRF temporal correction method.
Results
7T BH CVR
maps for a patient obtained pre-correction (i.e. before application of the temporal
HRF correction algorithm) and post-correction (i.e. after temporal HRF correction)
are depicted along with the corresponding 3T BH CVR map in Figure 1. Table 1
depicts the RMSEs between the time courses and the theoretical HRF which was
used for GLM analysis of 3T BH, uncorrected 7T BH and temporally corrected 7T
BH data. The RMSE reveals the superior goodness of fit following application of
temporal correction of the theoretical HRF.Discussion
In this preliminary study we have demonstrated the feasibility of
optimization of 7T BH CVR maps in the setting of brain tumors through use of a correction
algorithm based on novel temporal correction of the standard theoretical HRF
described by Birn and colleagues.Conclusion
In patients with brain tumors, application
of our novel HRF optimization method based on temporal correction of the HRF
provides superior quality BH CVR maps at ultra-high field.Acknowledgements
This work was supported by a Johns Hopkins Univ. Brain Science Institute
grant and partially by NIH grant R42 CA173976-02 (NCI).References
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