Quantification of whole‐brain oxygenation extraction fraction and cerebral metabolic rate of oxygen consumption in adults with sickle cell anemia using individual T₂‐based oxygenation calibrations

Abstract

Purpose: To evaluate different T 2 -oxygenation calibrations for estimating venous oxygenation in people with sickle cell anemia (SCA). Methods: Blood T 2 values were measured at 3 T in the internal jugular veins of 12 healthy volunteers and 11 SCA participants with no history of stroke, recent transfusion, or renal impairment. T 2 -oxygenation relationships of both sickled and normal blood samples were calibrated individually and compared with values generated from published models. After converting venous T 2 values to venous oxygenation, whole-brain oxygen extraction fraction and cerebral metabolic rate of oxygen were calculated. Results: Sickle blood samples' oxygenation values calculated from our individual calibrations agreed well with measurements using a blood analyzer, whereas previous T 2 calibrations based on normal blood samples showed 13%-19% underestimation. Meanwhile, oxygenation values calculated from previous grouped T 2 calibration for sickle blood agreed well with experimental measurement on averaged values, but showed up to 20% variation for several individual samples. Using individual T 2 calibrations, the whole-brain oxygen extraction fraction and cerebral metabolic rate of oxygen of SCA participants were 0.38 ± 0.08 and 172 ± 42 µmol/ min/100 g, respectively, which were comparable to those values measured on healthy volunteers. Conclusion: Our results confirm that sickle blood T 2 values not only depend on the hematocrit and oxygenation values, but also on other hematological factors.The individual T 2 calibrations minimized the effect of heterogeneity of sickle blood between different SCA populations and improved the accuracy of T 2 -based oximetry. | 1067LI et aL.

Validation of T2‐based oxygen extraction fraction measurement with 15O positron emission tomography

“…While this relationship is generally well-understood, 53 different calibration models have been proposed to convert blood T 2 to oxygenation. 10,11,33,54,55 In this work of healthy adults, we used a bovine blood model proposed by Lu et al, 33 which seems to have provided results in excellent agreement with the PET data. Bovine blood has characteristics similar to human blood.…”

“…We note that T 2 ‐based MR oximetry such as TRUST relies on the association between blood T 2 and oxygenation. While this relationship is generally well‐understood, 53 different calibration models have been proposed to convert blood T 2 to oxygenation 10,11,33,54,55 . In this work of healthy adults, we used a bovine blood model proposed by Lu et al, 33 which seems to have provided results in excellent agreement with the PET data.…”

“…Bovine and human hemoglobin both have two α polypeptide chains and two β chains, and both erythrocytes have a biconcave shape of similar diameters (5-6 μm for bovine, ~7 μm for human). 56,57 While reports have shown T 2 variations when using blood of different species, 10,33,54 some of them may be attributed to experimental conditions such as blood preparation procedure (circulating blood vs. static blood), pulse sequence (turbo-field-echo-T 2 vs. conventional T 2 ), and width of the T 2 -preparation RF pulses. A study directly comparing blood types while ensuring other experimental conditions constant is needed to further elucidate this issue.…”

“…Therefore, for adult populations with typical erythrocytes and normal‐range hematocrits, the bovine blood model used appears appropriate. For patient populations with atypical red blood cells, such as patients with sickle cell disease or neonatal patients, other calibration models should be carefully chosen 10,11,54,55 …”

“…Cerebral oxygen extraction fraction (OEF) is a potential biomarker in a variety of diseases, such as Alzheimer's disease, 1,2 cerebrovascular diseases, [3][4][5][6][7][8] multiple sclerosis, 9 and sickle cell anemia. 3,[10][11][12] The current gold-standard for image-based OEF quantification inside the human brain is positron emission tomography (PET) with three different 15 O-labeled radiotracers, 13 including 15 O-labeled carbon monoxide (C 15 O) to estimate cerebral blood volume (CBV), 15 O-labeled water (H 2 15 O) to measure cerebral blood flow (CBF), and 15 O-labeled oxygen ( 15 O 2 ) to measure oxygen utilization. OEF is computed from the three in combination.…”