Hua-Shan Liu1,2,3,4, Abbas F Jawad5, Nina Laney6, Erum A Hartung7, Allison M Port8, Ruben C Gur9, Stephen Hooper10, Jerilynn Radcliffe11, Susan L Furth6,12, and John A Detre13
1Department of Neurology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, United States, 2Graduate Institute of Clinical Medicine, Taipei Medical University, Taipei, Taiwan, 3Department of Medical Imaging, Taipei Medical University Hospital, Taipei, Taiwan, 4Translational Imaging Research Center, Taipei Medical University, Taipei, Taiwan, 5Department of Pediatrics, Children’s Hospital of Philadelphia, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, United States, 6Division of Nephrology, Children’s Hospital of Philadelphia, Philadelphia, PA, United States, 7Division of Nephrology, Department of Pediatrics, Children’s Hospital of Philadelphia, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, United States, 8Brain Behavior Laboratory, Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, United States, 9Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, United States, 10Department of Allied Health Sciences, University of North Carolina School of Medicine, Chapel Hill, NC, United States, 11Division of Developmental and Behavioral Pediatrics, Department of Pediatrics, Children's Hospital of Philadelphia, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, United States, 12Division of Nephrology, Departments of Pediatrics and Epidemiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, United States, 13Departments of Neurology and Radiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, United States
Synopsis
We evaluated three
different approaches to blood T1 used to model ASL CBF measurements in a cohort
of children with chronic kidney disease and controls. We observed significant
changes in blood T1 depending on the approach used, leading to different
results for both sex and group differences in CBF. Our results highlight the
importance of blood T1 in ASL CBF quantification and suggest that hematocrit-based
T1 may be the optimal approach if hematocrit can be measured at the time of the
scan, especially for studies in patients with anemia.PURPOSE
Arterial
spin labeling (ASL) provides quantitative tissue perfusion information for
basic and clinical research
1, 2. Models linking ASL signal changes to quantitative perfusion include several
other parameters that must be measured or assumed. One such parameter is blood
T1, used to correct for signal decay between labeling and imaging. In ASL
quantification blood T1 is typically assumed using either a fixed value
3 or a modeled value based on age and sex
4. An alternative strategy is to calculate blood T1 based on measured
hematocrit
3 since blood T1 depends on hematocrit
5. This may be critically important, for studies in patients with anemia. Here we evaluated these approaches to blood T1 used to model ASL CBF
measurements in a cohort of children with chronic kidney disease (CKD) and
controls.
METHODS
61 patients with CKD
(defined as estimated glomerular filtration rate, eGFR <90 ml/min/1.73m
2
using modified Schwartz formula, on dialysis, and post-transplant) and 47
age-matched control subjects were included in this analysis (Table 1). A pCASL labeling scheme was implemented with
2D GE EPI sequence on a Siemens 3T scanner (Verio) using a 32-channel head coil.
The labeling and control RF duration was 1.5 sec with post-labeling delay of
1.2 sec. Multi-slice perfusion maps were acquired with the following parameters:
TR/TE = 4000/17 ms, flip angle=900, bandwidth = 1532 Hz/pixel, slice
thickness = 4mm with 25% distance factor, matrix size = 64×64, FOV = 240×240
mm
2, slice number = 20, GRAPPA factor = 2 in Ky, and 40 label/control pairs. Quantitative
CBF values were calculated by using a standard one-compartment perfusion model
6. Blood T1 values were implemented using three
different approaches: (1) a fixed value of 1664 msec for all subjects, (2) Hct-based
estimation using the equation derived by Lu et al.: T1=1/(0.52*Hct+0.38)
3 based on a Hct
measurement performed at the time of the MRI scan, and (3) age+sex based
estimation according to the method derived by Wu et al. (T1=2115.6-21.5*age-73.3*sex, where
sex=1 for males and 0 for females)
4.
RESULTS
Table
2 shows the results of calculated T1 and CBF values for each subgroup using different
T1 methods. By using paired t-test, blood T1 based on both Hct and age+sex showed
significant larger T1 values than the assumed value (P<0.05), except in
control males where the fixed value of T1 was very close to the result using
Hct correction (P=0.756). In controls, age+sex based estimation overestimated
T1 for both males and females as compared with Hct method (Table 3, P=0.0002
and P <0.00005 for males and females, respectively). In the CKD group, age+sex
based T1 estimation was closer to HCT-corrected T1, but T1 was still
overestimated (Table 3, P=0.86 and P=0.04 for males and females, respectively). Use of a fixed T1 value without considering the
effect of Hct produced strong group differences in CBF between CKD and controls
(P=0.007, 0.048 and 0.0009 for GM, WM and global CBF, respectively, Figure 1), and
Hct based corrected T1 still showed significant group differences in GM and
global CBF (P=0.010 and 0.012, respectively, Figure 1) while age+sex estimated T1
did not yield any significant group differences (P=0.130, 0.669, 0.168 for GM,
WM and global CBF, respectively, Figure 1). In controls, females showed higher
CBF values as compared with males using all of the T1 methods, though
significant differences using fixed T1 (P=0.02) were reduced in HCT based
corrected T1 method (P=0.11). Sex differences in CBF are not present in CKD
using any of the models (P>0.05).
DISCUSSION
We observed significant changes in blood T1 depending on the approach used,
leading to different results for both sex and group differences in CBF. Sex
differences of CBF in controls using fixed T1 were reduced with Hct based T1
correction, suggesting that at least some of these effects are mediated by Hct.
Age+sex based T1 estimation eliminated group differences in CBF expected due to
known rheological effects of anemia
7. The absence of sex difference in CBF in patients with
CKD using any of the models is consistent with delayed sexual differentiation
that is known to occur in children with CKD
8. These results
highlight the importance of blood T1 in ASL CBF quantification and suggest that
Hct-based T1 may be the optimal approach if Hct can be measured at the time of
the scan.
Acknowledgements
This
project is funded, in part, under a Commonwealth Universal Research Enhancement
grant with the Pennsylvania Department of Health, # SAP 4100054843. The
Department specifically disclaims responsibility for any analyses,
interpretations or conclusions.
Study
data were collected and managed using REDCap electronic data capture tools
hosted at The Children’s Hospital of Philadelphia. REDCap (Research Electronic
Data Capture) (Paul A. Harris, Robert
Taylor, Robert Thielke, Jonathon Payne, Nathaniel Gonzalez, Jose G. Conde,
Research electronic data capture (REDCap) - A metadata-driven methodology and
workflow process for providing translational research informatics support, J
Biomed Inform. 2009 Apr;42(2):377-81.) is a secure, web-based application
designed to support data capture for research studies, providing 1) an
intuitive interface for validated data entry; 2) audit trails for tracking data
manipulation and export procedures; 3) automated export procedures for seamless
data downloads to common statistical packages; and 4) procedures for importing
data from external sources.
The
Clinical and Translational Research Center at the Children’s Hospital of
Philadelphia is supported by the National Center for Research Resources and the
National Center for Advancing Translational Sciences, National Institutes of
Health, through Grants UL1RR024134 and UL1TR000003. The content is solely the
responsibility of the authors and does not necessarily represent the official
views of the NIH.
This work was also supported in part by the
National Institutes of Health (grants MH080729 and EB015893).
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