This study aimed to validate T2- and susceptibility-based cerebral venous oxygen saturation (SvO2) measurements with the clinical standard, jugular vein catheterization. T2-relaxation-under-tagging (TRUST) and susceptibility-based oximetry (SBO) were performed on two healthy subjects with jugular catheterization and eleven subjects without catheterization under baseline, hypoxia and hypercapnia. TRUST tightly agreed with the jugular reference under hypercapnia but significantly underestimated SvO2 under baseline and hypoxia. Bias between SBO and the reference was independent on the physiological state. A proportional bias was observed comparing TRUST and SBO. The results suggested caution for inter-subject comparison of absolute SvO2 measurements using either TRUST or SBO.
Thirteen healthy subjects (24–35 years) were studied after providing written informed consent under an IRB approved protocol. Blood hematocrit (Hct) was measured on the same day of their MRI scans. MRI was performed on a clinical 3T scanner (Philips Achieva) with a 32-channel head coil. Subjects were placed on a 2-liter reservoir rebreathing circuit and imaged under three oxygenation conditions: 1) hypoxia (12% O2 and 88% N2), 2) hypercapnia (5% CO2 and room air), and 3) baseline (room air). Eleven subjects were scanned without catheterization under these three oxygenation conditions. Test-retest agreement was assessed under baseline.
Two subjects were scanned after internal jugular vein catheterization with 3-French tracker catheter. During the entire imaging session, blood was drawn from the catheter every 3 min by a cardiologist for SvO2 measurement using a portable co-oximeter (Accriva Diagnostics, Avoximeter 4000). The co-oximeter measurement was used as ground truth. The sequence (Table 1), calibration model and image processing used for TRUST were provided by Lu et al2. Following a recent system upgrade, the post-saturation module in the TRUST sequence12 was inadvertently deactivated, forcing us to retrospectively correct the resultant T2 underestimation via Bloch simulation. SBO data were acquired using a 3D multi-echo GRE sequence (Table 1) with full flow compensation13 and processed in a 3D manner (Figure 1). The magnetic field shift inside the vessel,$$$\Delta B_0$$$, was converted to SvO2 using:
$$\Delta B_0=\frac{1}{6}\text{Hct}\cdot\Delta\chi_{do} (1-S_vO_2) \cdot (3cos^2\theta - 1)\cdot B_0$$
where $$$\Delta\chi_{do} = 4 \pi(0.27)$$$ ppm, and $$$\theta$$$ is the vessel tilt angle with respect to the main B0 field.
TRUST and SBO had excellent test-retest agreement of 1.4% and 2.2%. In Figure 2, SvO2-TRUST and SvO2-SBO were highly correlated (Pearson r = 0.91, R2 = 0.84). However, Bland-Altman analysis revealed a significant proportional bias (p < 0.01). Compared with SBO, TRUST presented greater response of SvO2 to stimulus, particularly for the hypercapnia challenge.
In both subjects scanned with jugular catheterization, SvO2-TRUST measurements closely matched the jugular reference under hypercapnia but were lower than reference under hypoxia and baseline (Figure 3A-B). In contrast, the discrepancy between SvO2-SBO and reference was independent on the physiological states. On average, the bias between SvO2-TRUST and the reference was -9.2% (p < 0.0001), while the bias between SvO2-SBO and reference was -1.0% (p = 0.45) (Figure 3C-D).
The proportional bias between TRUST and SBO has been suggested by several prior studies10,14, but we demonstrated it more convincingly with the broad range of oxygenation produced. The large discrepancy between TRUST and the jugular reference is unlikely to relate to physiological distinction between the two veins. The saturation difference between jugular vein and SSS has been well characterized (only 2-3% at baseline15). We suspect that the TRUST bias may originate from the calibration models themselves3,16,17, which were obtained from in-vitro blood experiments that may fail to mimic the changing venous blood environment under gas challenges (e.g. venous pCO2 varied from 30-55 torr in this experiment).
Although SBO had smaller bias from the jugular reference compared to TRUST, SBO has major challenges for use in SSS. The acquisition of 3D multi-echo phase data allowed us to perform 2D SBO processing for all axial slices with vessel tilt < 20°. The predicted SvO2 values varied by an absolute saturation range of 22% along the slice direction (Figure 4). Such high variance along the slice direction will lessen the confidence of using 2D SBO processing for absolute SvO2 quantification.
Conclusion
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