Diminished cerebral oxygen extraction and metabolic rate in sickle cell disease using T2 relaxation under spin tagging MRI

Abstract

Purpose T2 MRI oximetry can non-invasively determine oxygen saturation (Y) but requires empirical MR calibration models to convert the measured blood transverse relaxation (T2b) into Y. The accuracy of existing T2b models in the presence of blood disorders such as sickle cell disease (SCD) remains unknown. Methods A Carr Purcell Meiboom Gill T2 preparation sequence was used to make 83 whole blood measurements from 11 subjects with SCD in order to derive an ex-vivo hemoglobin S (HbS) T2b model. Forearm venous blood gas, sagittal sinus T2 (T2 Relaxation Under Spin Tagging) and total brain blood flow (phase contrast MRI) were measured in 37 healthy controls and 33 SCD subjects (age 24.6 ± 10.2 years). Cerebral oxygen saturation, extraction fraction and metabolic rate estimates were calculated using three separate T2b models. Cerebral and forearm oxygen extraction fraction were compared. Results Ex-vivo, SCD blood had greater saturation dependent relaxivity than control blood, with a weak dependence on HbS and no dependence on hematocrit. In-vivo, the HbS T2b model predicted Yv values with lowest coefficient of variation (compared to existing T2b models) and the strongest correlation with peripheral venous oximetry (r2=.29). The HbS T2b model predicted systematically higher Yv measurements in SCD patients (73 ± 5 and 61 ± 6, p<0.0001) which was mirrored by peripheral venous measurements (75 ± 20 and 45 ± 20, p<0.0001). Conclusion Cerebral and peripheral oxygen extraction are decreased in SCD patients, suggesting either blood flow is increased beyond metabolic demands or the presence of physiological arterial-venous shunting.

Pseudo continuous arterial spin labeling quantification in anemic subjects with hyperemic cerebral blood flow

“…However, the appearance of labeled blood in the sagittal sinus implies an arteriovenous transit time of <3.6 seconds (sum of label duration and delay), suggesting that a portion of the bolus may have experienced insufficient residence time in capillary beds for normal gas and nutrient exchange (microvascular shunting). Previous groups have observed a similar phenomenon in subjects with known arterio-venous malformations (40) and young, sickle cells patients(41,42) but we demonstrate that the effect is also present in anemic patients with normal hemoglobin. We propose that rapid arterio-venous transit may represent an independent biomarker of disease severity as well as a source of error between ASL and PC CBF estimate but we lacked statistical power to address this possibility.…”

In vivo validation of T2‐ and susceptibility‐based SvO2 measurements with jugular vein catheterization under hypoxia and hypercapnia

“…However, before the previously discussed biases are confirmed and corrected, caution should be placed when TRUST is used or compared under different physiological conditions. For diseases that provide drastically different blood properties from existing in‐vitro calibration materials, like sickle cell anemia, calibration models should also be reconsidered …”

“…Cerebral oxygen extraction fraction (OEF), defined as the difference between arterial and venous oxygen saturations (S a O 2 and S v O 2 ), is an important parameter for the assessment of brain oxygen consumption and tissue viability. Accurate OEF measurement is required to model the pathophysiology and optimize the treatment of neurological disorders with altered cerebral hemodynamics, including stroke, chronic anemia, and neurodegenerative disorders such as multiple sclerosis . While measurement of S a O 2 can be easily performed with pulse oximetry, standard measurement of cerebral S v O 2 is challenging because of the risks associated with invasive procedures.…”

“…MIAO et Al. cerebral hemodynamics, including stroke, 1 chronic anemia, 2,3 and neurodegenerative disorders such as multiple sclerosis. 4 While measurement of S a O 2 can be easily performed with pulse oximetry, standard measurement of cerebral S v O 2 is challenging because of the risks associated with invasive procedures.…”

“…Despite the increasing applications of TRUST and SBO, [2][3][4][16][17][18] in vivo validation of these two techniques for global cerebral S v O 2 measurement is still lacking. Prior validations of TRUST and SBO were based on cross-correlation with other physiological measurements 9,[16][17][18] rather than on the clinical gold standards.…”