Blood T1 and CBF Quantification in ASL MRI
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 value3 or a modeled value based on age and sex4. An alternative strategy is to calculate blood T1 based on measured hematocrit3 since blood T1 depends on hematocrit5. 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/1.73m2 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 mm2, 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 model6. 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 anemia7. 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 CKD8. 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).

References

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4. Wu WC, Jain V, Li C, Giannetta M, Hurt H, Wehrli FW, et al. In vivo venous blood t1 measurement using inversion recovery true-fisp in children and adults. Magn Reson Med. 2010;64:1140-1147

5. Gevers S, Nederveen AJ, Fijnvandraat K, van den Berg SM, van Ooij P, Heijtel DF, et al. Arterial spin labeling measurement of cerebral perfusion in children with sickle cell disease. J Magn Reson Imaging. 2012;35:779-787

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Figures

Table 1. Subject demographics and hematocrit measurements. *P<0.05

Table 2. Calculated CBF and T1 values using three different models.

Table 3. Comparison of calculated T1 values using different methods. HCT based: Hct-based estimation using the equation derived by Lu et al.: T1=1/(0.52*Hct+0.38); Age+Sex based: 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); fixed T1: a fixed value of 1664 msec for all subjects. *P<0.05

Figure 1. Gray matter (GM) CBF measurements using three different T1 methods (fixed T1, Hct based, and age+sex based) in each subgroup (males and females in CKD, and males and females in controls). *P<0.05



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