Zachary B. Rodgers

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.

Rapid T2- and susceptometry-based CMRO2 quantification with interleaved TRUST (iTRUST)

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/100g/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.

Comparison of MRI Methods for Measuring Whole-Brain Venous Oxygen Saturation

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).

MRI-based methods for quantification of the cerebral metabolic rate of oxygen.

The brain depends almost entirely on oxidative metabolism to meet its significant energy requirements. As such, the cerebral metabolic rate of oxygen (CMRO2) represents a key measure of brain function. Quantification of CMRO2 has helped elucidate brain functional physiology and holds potential as a clinical tool for evaluating neurological disorders including stroke, brain tumors, Alzheimer’s disease, and obstructive sleep apnea. In recent years, a variety of magnetic resonance imaging (MRI)-based CMRO2 quantification methods have emerged. Unlike positron emission tomography – the current “gold standard” for measurement and mapping of CMRO2 – MRI is non-invasive, relatively inexpensive, and ubiquitously available in modern medical centers. All MRI-based CMRO2 methods are based on modeling the effect of paramagnetic deoxyhemoglobin on the magnetic resonance signal. The various methods can be classified in terms of the MRI contrast mechanism used to quantify CMRO2: T2*, T2′, T2, or magnetic susceptibility. This review article provides an overview of MRI-based CMRO2 quantification techniques. After a brief historical discussion motivating the need for improved CMRO2 methodology, current state-of-the-art MRI-based methods are critically appraised in terms of their respective tradeoffs between spatial resolution, temporal resolution, and robustness, all of critical importance given the spatially heterogeneous and temporally dynamic nature of brain energy requirements.

Quantitative CMR markers of impaired vascular reactivity associated with age and peripheral artery disease

BackgroundThe aim of this study was to develop and evaluate an integrated CMR method incorporating dynamic oximetry, blood flow and pulse-wave velocimetry to assess vascular reactivity in patients with peripheral artery disease (PAD) and healthy controls.Methods and resultsThe study population consisted of young healthy subjects (YH, 30 ± 7 yrs, N = 19),PAD (71 ± 9 yrs, N = 38), and older healthy controls (OHC, 68 ± 9 yrs, N = 43). Peripheral vascular reactivity was evaluated with two methods, time-resolved quantification of blood flow velocity and oxygenation level in the femoral artery and vein, respectively, performed simultaneously both at rest and hyperemia. Aortic stiffness was assessed via pulse-wave velocity. Oximetric data showed that compared to OHC, the time-course of the hemoglobin oxygen saturation in PAD patients had longer washout time (28.6 ± 1.2 vs 16.9 ± 1.1 s, p < 0.0001), reduced upslope (0.60 ± 0.1 vs 1.3 ± 0.08 HbO2/sec, p < 0.0001) and lower overshoot (8 ± 1.4 vs 14 ± 1.2 HbO2, p = 0.0064). PAD patients also had longer-lasting antegrade femoral artery flow during hyperemia (51 ± 2.1 vs 24 ± 1.8 s, p < 0.0001), and reduced peak-to-baseline flow rate (3.1 ± 0.5 vs 7.4 ± 0.4, p < 0.0001). Further, the pulsatility at rest was reduced (0.75 ± 0.32 vs 5.2 ± 0.3, p < 0.0001), and aortic PWV was elevated (10.2 ± 0.4 vs 8.1 ± 0.4 m/s, p = 0.0048).ConclusionThe proposed CMR protocol quantifies multiple aspects of vascular reactivity and represents an initial step toward development of a potential tool for evaluating interventions, extrapolating clinical outcomes and predicting functional endpoints based on quantitative parameters.

Cerebral metabolic rate of oxygen in obstructive sleep apnea at rest and in response to breath-hold challenge

Obstructive sleep apnea (OSA) is associated with extensive neurologic comorbidities. It is hypothesized that the repeated nocturnal apneas experienced in patients with OSA may inhibit the normal apneic response, resulting in hypoxic brain injury and subsequent neurologic dysfunction. In this study, we applied the recently developed OxFlow MRI method for rapid quantification of cerebral metabolic rate of oxygen (CMRO2) during a volitional apnea paradigm. MRI data were analyzed in 11 OSA subjects and 10 controls (mean ± SD apnea-hypopnea index (AHI): 43.9 ± 18.1 vs. 2.9 ± 1.6 events/hour, P < 0.0001; age: 53.8 ± 8.2 vs. 45.3 ± 8.5 years, P = 0.027; BMI: 36.6 ± 4.4 vs. 31.9 ± 2.2 kg/m2, P = 0.0064). Although total cerebral blood flow and arteriovenous oxygen difference were not significantly different between apneics and controls (P > 0.05), apneics displayed reduced baseline CMRO2 (117.4 ± 37.5 vs. 151.6 ± 29.4 µmol/100 g/min, P = 0.013). In response to apnea, CMRO2 decreased more in apneics than controls (−10.9 ± 8.8 % vs. −4.0 ± 6.7 %, P = 0.036). In contrast, group differences in flow-based cerebrovascular reactivity were not significant. Results should be interpreted with caution given the small sample size, and future studies with larger independent samples should examine the observed associations, including potential independent effects of age or BMI. Overall, these data suggest that dysregulation of the apneic response may be a mechanism for OSA-associated neuropathology.

Cerebrovascular reactivity measured with arterial spin labeling and blood oxygen level dependent techniques.

PURPOSE To compare cerebrovascular reactivity (CVR) quantified with pseudo-continuous arterial spin labeling (pCASL) and blood oxygen level dependent (BOLD) fMRI techniques. MATERIALS AND METHODS Sixteen healthy volunteers (age: 37.8±14.3years; 6 women and 10 men; education attainment: 17±2.1years) were recruited and completed a 5% CO2 gas-mixture breathing paradigm at 3T field strength. ASL and BOLD images were acquired for CVR determination assuming that mild hypercapnia does not affect the cerebral metabolic rate of oxygen. Both CVR quantifications were derived as the ratio of the fractional cerebral blood flow (CBF) or BOLD signal change over the change in end-tidal CO2 pressure. RESULTS The absolute CBF, BOLD and CVR measures were consistent with literature values. CBF derived CVR was 5.11±0.87%/mmHg in gray matter (GM) and 4.64±0.37%/mmHg in parenchyma. BOLD CVR was 0.23±0.04%/mmHg and 0.22±0.04%/mmHg for GM and parenchyma respectively. The most significant correlations between BOLD and CBF-based CVRs were also in GM structures, with greater vascular response in occipital cortex than in frontal and parietal lobes (6.8%/mmHg versus 4.5%/mmHg, 50% greater). Parenchymal BOLD CVR correlated significantly with the fractional change in CBF in response to hypercapnia (r=0.61, P=0.01), suggesting the BOLD response to be significantly flow driven. GM CBF decreased with age in room air (-5.58mL/100g/min per decade for GM; r=-0.51, P=0.05), but there was no association of CBF with age during hypercapnia. A trend toward increased pCASL CVR with age was observed, scaling as 0.64%/mmHg per decade for GM. CONCLUSION Consistent with previously reported CVR values, our results suggest that BOLD and CBF CVR techniques are complementary to each other in evaluating neuronal and vascular underpinning of hemodynamic processes.

Method for rapid MRI quantification of global cerebral metabolic rate of oxygen.

A recently reported quantitative magnetic resonance imaging (MRI) method denoted OxFlow has been shown to be able to quantify whole-brain cerebral metabolic rate of oxygen (CMRO2) by simultaneously measuring oxygen saturation (S v O 2 ) in the superior sagittal sinus and cerebral blood flow (CBF) in the arteries feeding the brain in 30 seconds, which is adequate for measurement at baseline but not necessarily in response to neuronal activation. Here, we present an accelerated version of the method (referred to as F-OxFlow) that quantifies CMRO2 in 8 seconds scan time under full retention of the parent methods capabilities and compared it with its predecessor at baseline in 10 healthy subjects. Results indicate excellent agreement between both sequences, with mean bias of 2.2% (P = 0.18, two-tailed t-test), 3.4% (P = 0.08, two-tailed t-test), and 2.0% (P = 0.56, two-tailed t-test) for SvO2, CBF, and CMRO2, respectively. F-OxFlows potential to monitor dynamic changes in SvO2, CBF, and CMRO2 is illustrated in a paradigm of volitional apnea applied to five of the study subjects. The sequence captured an average increase in SvO2, CBF, and CMRO2 of 10.1 ± 2.5%, 43.2 ± 9.2%, and 7.1 ± 2.2%, respectively, in good agreement with literature values. The method may therefore be suited for monitoring alterations in CBF and SvO2 in response to neurovascular stimuli.

Susceptibility-based time-resolved whole-organ and regional tissue oximetry.

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 non‐steady‐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. Copyright