We present a technique for quantifying global cerebral metabolic rate of oxygen consumption (CMRO2) in absolute physiologic units at 3-second temporal resolution and apply the technique to quantify the dynamic CMRO2 response to volitional apnea. Temporal resolution of 3 seconds was achieved via a combination of view sharing and superior sagittal sinus-based estimation of total cerebral blood flow (tCBF) rather than tCBF measurement in the neck arteries. These modifications were first validated in three healthy adults and demonstrated to produce minimal errors in image-derived blood flow and venous oxygen saturation (SvO2) values. The technique was then applied in 10 healthy adults during an apnea paradigm of three repeated 30-second breath-holds. Subject-averaged baseline tCBF, arteriovenous oxygen difference (AVO2D), and CMRO2 were 48.6 ± 7.0 mL/100 g per minute, 29.4 ± 3.4 %HbO2, and 125.1 ± 11.4 μmol/100 g per minute, respectively. Subject-averaged maximum changes in tCBF and AVO2D were 43.5 ± 9.4% and -32.1 ± 5.7%, respectively, resulting in a small (6.0 ± 3.5%) but statistically significant (P=0.00044, two-tailed t-test) increase in average end-apneic CMRO2. This method could be used to investigate neurometabolic-hemodynamic relationships in normal physiology, to better define the biophysical origins of the BOLD signal, and to quantify neurometabolic responsiveness in diseases of altered neurovascular reactivity.

BackgroundThe function of the peripheral microvascular may be interrogated by measuring perfusion, tissue oxygen concentration, or venous oxygen saturation (SvO2) recovery dynamics following induced ischemia. The purpose of this work is to develop and evaluate a magnetic resonance (MR) technique for simultaneous measurement of perfusion, SvO2, and skeletal muscle T2*.MethodsPerfusion, Intravascular Venous Oxygen saturation, and T2* (PIVOT) is comprised of interleaved pulsed arterial spin labeling (PASL) and multi-echo gradient-recalled echo (GRE) sequences. During the PASL post-labeling delay, images are acquired with a multi-echo GRE to quantify SvO2 and T2* at a downstream slice location. Thus time-courses of perfusion, SvO2, and T2* are quantified simultaneously within a single scan. The new sequence was compared to separately measured PASL or multi-echo GRE data during reactive hyperemia in five young healthy subjects. To explore the impairment present in peripheral artery disease patients, five patients were evaluated with PIVOT.ResultsComparison of PIVOT-derived data to the standard techniques shows that there was no significant bias in any of the time-course-derived metrics. Preliminary data show that PAD patients exhibited alterations in perfusion, SvO2, and T2* time-courses compared to young healthy subjects.ConclusionSimultaneous quantification of perfusion, SvO2, and T2* is possible with PIVOT. Kinetics of perfusion, SvO2, and T2* during reactive hyperemia may help to provide insight into the function of the peripheral microvasculature in patients with PAD.

The magnetism of hemoglobin – being paramagnetic in its deoxy and diamagnetic in its oxy state – offers unique opportunities to probe oxygen metabolism in blood and tissues. The magnetic susceptibility χ of blood scales linearly with blood oxygen saturation, which can be obtained by measuring the magnetic field ΔB of the intravascular MR signal relative to tissue. In contrast to χ the induced field ΔB is non-local. Therefore, to obtain the intravascular susceptibility Δχ relative to adjoining tissue from the measured ΔB demands solution of an inverse problem. Fortunately, for ellipsoidal structures, to which a straight, cylindrically shaped blood vessel segment conforms, the solution is trivial. The article reviews the principle of MR susceptometry-based blood oximetry. It then discusses applications for quantification of whole-brain oxygen extraction – typically on the basis of a measurement in the superior sagittal sinus – and, in conjunction with total cerebral blood flow, the cerebral metabolic rate of oxygen (CMRO2). By simultaneously measuring flow and venous oxygen saturation (SvO2) a temporal resolution of a few seconds can be achieved, allowing the study of the response to nonsteady-state challenges such as volitional apnea. Extensions to regional measurements in smaller cerebral veins are also possible, as well as voxelwise quantification of venous blood saturation in cerebral veins accomplished by quantitative susceptibility mapping (QSM) techniques. Applications of susceptometry-based oximetry to studies of metabolic and degenerative disorders of the brain are reviewed. Lastly, the technique is shown to be applicable to other organ systems such as the extremities using SvO2 as a dynamic tracer to monitor the kinetics of the microvascular response to induced ischemia.

Purpose In this work, we compare susceptometry-based oximetry (SBO) and two T2-based methods for estimating resting baseline SvO2 in the superior sagittal sinus (SSS). Methods SBO is a field-mapping technique whereas in T2-based methods the intravascular blood signal is isolated either with velocity-encoded projections [projection-based T2 (PT2)] or a tag-control scheme [T2-relaxation under spin tagging (TRUST)] after T2-preparation. The measurements were performed on twelve healthy subjects (mean age=33±6 years) at 3 Tesla field strength. The reliability, precision, and reproducibility were examined for the three techniques. Results The mean (± standard deviation) SvO2 quantified by SBO, PT2, and TRUST were found to be 65.9±3.3, 65.6±3.5, and 63.2±4.1%. The standard deviation (SD) for 10 consecutive measurements in the quantified SvO2 was less than 2.7%, 4.7%, and 5.0% for SBO, PT2, and TRUST across all subjects. In testing reproducibility across different days, the resulting SDs were 2.6, 3.5, and 2.0% for SBO, PT2, and TRUST. Conclusion The results indicate that all three SvO2 quantification techniques to be reliable with good agreement between PT2 and SBO while TRUST yielded slightly lower values compared with the other two techniques.

Susceptometry-based oximetry (SBO) and T2-relaxation-under-spin-tagging (TRUST) are two promising methods for quantifying the cerebral metabolic rate of oxygen (CMRO2), a critical parameter of brain function. We present a combined method, interleaved TRUST (iTRUST), which achieves rapid, simultaneous quantification of both susceptometry- and T2-based CMRO2 via insertion of a flow-encoded, dual-echo gradient-recalled echo (OxFlow) module within the T1 recovery portion of the TRUST sequence. In addition to allowing direct comparison between SBO- and TRUST-derived venous oxygen saturation (Yv) values, iTRUST substantially improves TRUST temporal resolution for CMRO2 quantification and obviates the need for a separate blood flow measurement following TRUST acquisition. iTRUST was compared directly to TRUST and OxFlow alone in three resting subjects at baseline, exhibiting close agreement with the separate techniques and comparable precision. These baseline data as well as simulation results support the use of two instead of the traditional four T2 preparation times for T2 fitting, allowing simultaneous quantification of susceptometry- and T2-based Yv (and CMRO2) with three- and six-second temporal resolution, respectively. In 10 young healthy subjects, iTRUST was applied during a 5% CO2 gas mixture-breathing paradigm. T2-based Yv values were lower at baseline relative to susceptometry (62.3 ± 3.1 vs. 66.7 ± 5.1 %HbO2, P < 0.05), but increased more in response to hypercapnia. As a result, T2-based CMRO2 decreased from 140.4 ± 9.7 to 120.0 ± 9.5 μMol/100 g/min, a significant − 14.6 ± 3.6% response (P < 0.0001), whereas susceptometry-based CMRO2 changed insignificantly from 123.4 ± 18.7 to 127.9 ± 25.7, a 3.3 ± 9.7% response (P = 0.31). These differing results are in accord with previous studies applying the parent OxFlow or TRUST sequences individually, thus supporting the reliability of iTRUST but also strongly suggesting that a systematic bias exists between the susceptometry- and T2-based Yv quantification techniques.