Calibration of T2 oximetry MRI for subjects with sickle cell disease

Abstract

Purpose: Cerebral T₂ oximetry is a non-invasive imaging method to measure blood T₂ and cerebral venous oxygenation. Measured T₂ values are converted to oximetry estimates using carefully validated and potentially disease-specific calibrations. In sickle cell disease, red blood cells have abnormal cell shape and membrane properties that alter T₂ oximetry calibration relationships in clinically meaningful ways. Previous in vitro works by two independent groups established potentially competing calibration models.

Methods: This study analyzed pooled datasets from these two studies to establish a unified and more robust sickle-specific calibration to serve as a reference standard in the field.

Results: Even though the combined calibration did not demonstrate statistical superiority compared to previous models, the calibration was unbiased compared to blood-gas co-oximetry and yielded limits of agreement of (-10.1%, 11.6%) in non-transfused subjects with sickle cell disease. In transfused patients, this study proposed a simple correction method based on individual hemoglobin S percentage that demonstrated reduced bias in saturation measurement compared to previous uncorrected sickle calibrations.

Conclusion: The combined calibration is based on a larger range of hematocrit, providing greater confidence in the hematocrit-dependent model parameters, and yielded unbiased estimates to blood-gas co-oximetry measurements from both sites. Additionally, this work also demonstrated the need to correct for transfusion in T₂ oximetry measurements for hyper-transfused sickle cell disease patients and proposes a correction method based on patient-specific hemoglobin S concentration.

Keywords: T2 oximetry; calibration; sickle cell disease; venous saturation.

Figure 1.

HbS-specific Li-Bush calibration for non-transfused SCD patients. Linear dependence of (A) A and (B) B coefficients on hematocrit using pooled datasets from Bush et al. and Li et al.

Figure 2.

Individual and group sickle calibration models in a subset of 2 subjects from Li et al. and 2 non-transfused HbSS subjects from Bush et al. Individual calibration data (black filled circles) were fitted with individual calibration (dotted line), Li population calibration (red solid line), Bush population calibration (blue), Li-Bush combined calibration (green), bovine calibration (purple) and HbA calibration (orange). In Li Subject 2, Bush Subjects 1 and 2, the blue Bush calibration overlaps and is plotted underneath the red Li-Bush combined calibration.

Figure 3.

Bland-Altman analyses of different calibration models on non-transfused SCD subjects (closed circle, 5 from Bush et al. and 11 from Li et al.) and transfused subjects (open circle, 3 from Bush et al.). Each data point represents a set of in vitro blood saturation measurement by cerebral T₂ oximetry and blood-gas co-oximetry. (A) Subject-specific calibration gave the highest accuracy and lowest bias but is infeasible for routine clinical use. (B) Bovine and (C) healthy human blood HbA models exhibited large bias and variance when used in subjects with sickle cell disease. Sickle-specific population models by (D) Bush et al. and (E) Li et al. displayed comparable results. Therefore, (F) a combined consensus Li-Bush HbS model was reported and recommended for use in non-transfused SCD subjects. (G) In hyper-transfused patients, subject-specific calibration yielded low bias and variance, whereas (H) the Li-Bush consensus sickle calibration displayed a bias in transfused subjects. To correct for this bias, (I) a mixture HbS-weighted model was developed that demonstrated a smaller bias for use in transfused SCD patients.