Michael C. Langham

MRI Estimation of Global Brain Oxygen Consumption Rate

Measuring the global cerebral metabolic rate of oxygen (CMRO2) is a valuable tool for assessing brain vitality and function. Measurement of blood oxygen saturation (HbO2) and flow in the major cerebral outflow and inflow vessels can provide a global estimate of CMRO2. We demonstrate a rapid noninvasive method for quantifying CMRO2 by simultaneously measuring venous oxygen saturation in the superior sagittal sinus with magnetic resonance susceptometry-based oximetry, a technique that exploits the intrinsic susceptibility of deoxygenated hemoglobin, and the average blood inflow rate with phase-contrast magnetic resonance imaging. The average venous HbO2, cerebral blood flow, and global CMRO2 values in eight healthy, normal study subjects were 64%±4%, 45.2±3.2 mL per 100 g per minute, and 127±7 μmol per 100 g per minute, respectively. These values are in good agreement with those reported in literature. The technique described is noninvasive, robust, and reproducible for in vivo applications, making it ideal for use in clinical settings for assessing the pathologies associated with dysregulation of cerebral metabolism. In addition, the short acquisition time (∼30 seconds) makes the technique suitable for studying the temporal variations in CMRO2 in response to physiologic challenges.

Rapid magnetic resonance measurement of global cerebral metabolic rate of oxygen consumption in humans during rest and hypercapnia

The effect of hypercapnia on cerebral metabolic rate of oxygen consumption (CMRO2) has been a subject of intensive investigation and debate. Most applications of hypercapnia are based on the assumption that a mild increase in partial pressure of carbon dioxide has negligible effect on cerebral metabolism. In this study, we sought to further investigate the vascular and metabolic effects of hypercapnia by simultaneously measuring global venous oxygen saturation (SvO2) and total cerebral blood flow (tCBF), with a temporal resolution of 30 seconds using magnetic resonance susceptometry and phase-contrast techniques in 10 healthy awake adults. While significant increases in SvO2 and tCBF were observed during hypercapnia (P < 0.005), no change in CMRO2 was noted (P > 0.05). Additionally, fractional changes in tCBF and end-tidal carbon dioxide (R2 = 0.72, P < 0.005), as well as baseline SvO2 and tCBF (R2 = 0.72, P < 0.005), were found to be correlated. The data also suggested a correlation between cerebral vascular reactivity (CVR) and baseline tCBF (R2 = 0.44, P = 0.052). A CVR value of 6.1% ± 1.6%/mm Hg was determined using a linear-fit model. Additionally, an average undershoot of 6.7% ± 4% and 17.1% ± 7% was observed in SvO2 and tCBF upon recovery from hypercapnia in six subjects.

Retrospective correction for induced magnetic field inhomogeneity in measurements of large-vessel hemoglobin oxygen saturation by MR susceptometry.

MR susceptometry‐based blood oximetry relies on phase mapping to measure the difference in magnetic susceptibility between intravascular blood and surrounding tissue. The main source of error in MR susceptometry is the static field inhomogeneity caused by an interface between air and tissue or between adjacent tissue types. High‐pass filtering has previously been used in conjunction with shimming to reduce the effect of low spatial‐frequency modulations of the phase caused by large‐scale induced magnetic fields. We demonstrate that high‐pass filtering is not optimum for MR susceptometry because the results are sensitive to filter size. We propose an alternative method that acquires data without scanner‐implemented default shimming, and fits, after appropriate weighting and masking, the static field inhomogeneity to a second‐order polynomial. Compared to shimming the retrospective correction technique improved agreement between hemoglobin saturations measured in different segments of a vessel (femoral versus popliteal artery and vein) from three standard errors to less than one. Magn Reson Med, 2008.

Accuracy and precision of MR blood oximetry based on the long paramagnetic cylinder approximation of large vessels

An accurate noninvasive method to measure the hemoglobin oxygen saturation (%HbO2) of deep‐lying vessels without catheterization would have many clinical applications. Quantitative MRI may be the only imaging modality that can address this difficult and important problem. MR susceptometry–based oximetry for measuring blood oxygen saturation in large vessels models the vessel as a long paramagnetic cylinder immersed in an external field. The intravascular magnetic susceptibility relative to surrounding muscle tissue is a function of oxygenated hemoglobin (HbO2) and can be quantified with a field‐mapping pulse sequence. In this work, the methods accuracy and precision was investigated theoretically on the basis of an analytical expression for the arbitrarily oriented cylinder, as well as experimentally in phantoms and in vivo in the femoral artery and vein at 3T field strength. Errors resulting from vessel tilt, noncircularity of vessel cross‐section, and induced magnetic field gradients were evaluated and methods for correction were designed and implemented. Hemoglobin saturation was measured at successive vessel segments, differing in geometry, such as eccentricity and vessel tilt, but constant blood oxygen saturation levels, as a means to evaluate measurement consistency. The average standard error and coefficient of variation of measurements in phantoms were <2% with tilt correction alone, in agreement with theory, suggesting that high accuracy and reproducibility can be achieved while ignoring noncircularity for tilt angles up to about 30°. In vivo, repeated measurements of %HbO2 in the femoral vessels yielded a coefficient of variation of less than 5%. In conclusion, the data suggest that %HbO2 can be measured reproducibly in vivo in large vessels of the peripheral circulation on the basis of the paramagnetic cylinder approximation of the incremental field. Magn Reson Med, 2009.

Evaluation of Cuff-Induced Ischemia in the Lower Extremity by Magnetic Resonance Oximetry

OBJECTIVES The aim of this study was to evaluate vascular function in the lower extremities by making direct time-course measurement of oxygen saturation in the femoral/popliteal arteries and veins during cuff-induced reactive hyperemia with magnetic resonance imaging-based oximetry. BACKGROUND Magnetic resonance imaging-based oximetry is a new calibration-free technique taking advantage of the paramagnetic nature of blood that depends on the volume fraction of deoxyhemoglobin in red blood cells. METHODS We compared post-occlusive blood oxygenation time-course of femoral/popliteal vessels in: 1) young healthy subjects (YH) (n = 10; mean ankle-brachial index [ABI] 1.0 +/- 0.1, mean age 30 +/- 7 years); 2) peripheral arterial disease (PAD) patients (n = 12; mean ABI 0.6 +/- 0.1, mean age 71 +/- 9 years); and 3) age-matched healthy control subjects (AHC) (n = 8; mean ABI 1.1 +/- 0.1, mean age 68 +/- 9 years). Blood oxygenation was quantified at 3.0-T field strength with a field mapping pulse sequence yielding the magnetic susceptibility difference between blood in the vessels and surrounding muscle tissue from which the intravascular blood oxygen saturation is computed as %HbO(2). RESULTS Significantly longer washout time (42 +/- 16 s vs. 14 +/- 4 s; p < 0.0001) and lower upslope (0.60 +/- 0.20 %HbO(2)/s vs. 1.32 +/- 0.41 %HbO(2)/s; p = 0.0008) were observed for PAD patients compared with healthy subjects (YH and AHC combined). Furthermore, greater overshoot was observed in YH than in AHC (21 +/- 8 %HbO(2) vs. 10 +/- 5 %HbO(2); p = 0.0116). CONCLUSIONS Post-occlusive transient changes in venous blood oxygenation might provide a new measure of vascular competence, which was found to be reduced in subjects with abnormal ABI, manifesting in prolonged recovery during the early phase of hyperemia.

High temporal resolution MRI quantification of global cerebral metabolic rate of oxygen consumption in response to apneic challenge.

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.

Combined measurement of perfusion, venous oxygen saturation, and skeletal muscle T2* during reactive hyperemia in the leg

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.

Accuracy of the cylinder approximation for susceptometric measurement of intravascular oxygen saturation

Susceptometry‐based MR oximetry has previously been shown suitable for quantifying hemoglobin oxygen saturation in large vessels for studying vascular reactivity and quantification of global cerebral metabolic rate of oxygen utilization. A key assumption underlying this method is that large vessels can be modeled as long paramagnetic cylinders. However, bifurcations, tapering, noncircular cross‐section, and curvature of these vessels produce substantial deviations from cylindrical geometry, which may lead to errors in hemoglobin oxygen saturation quantification. Here, the accuracy of the “long cylinder” approximation is evaluated via numerical computation of the induced magnetic field from 3D segmented renditions of three veins of interest (superior sagittal sinus, femoral and jugular vein). At a typical venous oxygen saturation of 65%, the absolute error in hemoglobin oxygen saturation estimated via a closed‐form cylinder approximation was 2.6% hemoglobin oxygen saturation averaged over three locations in the three veins studied and did not exceed 5% for vessel tilt angles <30° at any one location. In conclusion, the simulation results provide a significant level of confidence for the validity of the cylinder approximation underlying MR susceptometry‐based oximetry of large vessels. Magn Reson Med, 2012.

High temporal resolution in vivo blood oximetry via projection-based T2 measurement

Measuring venous oxygen saturation (HbO2) in large blood vessels can provide important information about oxygen delivery and its consumption in vital organs. Quantification of bloods T2 value via MR can be utilized to determine HbO2 noninvasively. We propose a fast method for in vivo blood T2 quantification via computing the complex difference of velocity‐encoded projections. As blood flows continuously, its signal can be robustly isolated from the surrounding tissue by computing the complex difference of two central k‐space lines with different velocity encodings. This resultant signal can then be measured as a function of echo time for rapidly quantifying T2 of blood. We applied the method to quantify HbO2 in three cerebral veins at rest and in one of the veins in response to hypercapnia. Average HbO2 measurements in superior sagittal sinus (SSS), straight sinus and internal jugular vein in the group were 63 ± 3%, 68 ± 4% and 65 ± 4%, respectively. Average HbO2 values in SSS during baseline, hypercapnia, and recovery were 63 ± 2%, 79 ± 5%, and 61 ± 3%, respectively. When compared with standard T2 quantification techniques, the proposed method is fast, reliable, and robust against partial volume effects. Magn Reson Med 70:785–790, 2013.

Assessing intracranial vascular compliance using dynamic arterial spin labeling

Vascular compliance (VC) is an important marker for a number of cardiovascular diseases and dementia, which is typically assessed in the central and peripheral arteries indirectly by quantifying pulse wave velocity (PWV), and/or pulse pressure waveform. To date, very few methods are available for the quantification of intracranial VC. In the present study, a novel MRI technique for in-vivo assessment of intracranial VC was introduced, where dynamic arterial spin labeling (ASL) scans were synchronized with the systolic and diastolic phases of the cardiac cycle. VC is defined as the ratio of change in arterial cerebral blood volume (ΔCBV) and change in arterial pressure (ΔBP). Intracranial VC was assessed in different vascular components using the proposed dynamic ASL method. Our results show that VC mainly occurs in large arteries, and gradually decreases in small arteries and arterioles. The comparison of intracranial VC between young and elderly subjects shows that aging is accompanied by a reduction of intracranial VC, in good agreement with the literature. Furthermore, a positive association between intracranial VC and cerebral perfusion measured using pseudo-continuous ASL with 3D GRASE MRI was observed independent of aging effects, suggesting loss of VC is associated with a decline in perfusion. Finally, a significant positive correlation between intracranial and central (aortic arch) VC was observed using an ungated phase-contrast 1D projection PWV technique. The proposed dynamic ASL method offers a promising approach for assessing intracranial VC in a range of cardiovascular diseases and dementia.