MRI evaluation of cerebral metabolic rate of oxygen (CMRO2) in obstructive sleep apnea.

Patients with obstructive sleep apnea (OSA) are at elevated risk of developing systemic vascular disease and cognitive dysfunction. Here, cerebral oxygen metabolism was assessed in patients with OSA by means of a magnetic resonance-based method involving simultaneous measurements of cerebral blood flow rate and venous oxygen saturation in the superior sagittal sinus for a period of 10 minutes at an effective temporal resolution of 1.3 seconds before, during, and after repeated 24-second breath-holds mimicking spontaneous apneas, yielding, along with pulse oximetry-derived arterial saturation, whole-brain CMRO2 via Fick's Principle. Enrolled subjects were classified based on their apnea-hypopnea indices into OSA (N = 31) and non-sleep apnea reference subjects (NSA = 21), and further compared with young healthy subjects (YH, N = 10). OSA and NSA subjects were matched for age and body mass index. CMRO2 was lower in OSA than in the YH group during normal breathing (105.6 ± 14.1 versus 123.7 ± 22.8 µmol O2/min/100g, P = 0.01). Further, the fractional change in CMRO2 in response to a breath-hold challenge was larger in OSA than in the YH group (15.2 ± 9.2 versus 8.5 ± 3.4%, P = 0.04). However, there was no significant difference in CMRO2 between OSA and NSA subjects. The data suggest altered brain oxygen metabolism in OSA and possibly in NSA as well.

Endogenous T1ρ cardiovascular magnetic resonance in hypertrophic cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is characterized by increased left ventricular wall thickness, cardiomyocyte hypertrophy, and fibrosis. Adverse cardiac risk characterization has been performed using late gadolinium enhancement (LGE), native T1, and extracellular volume (ECV). Relaxation time constants are affected by background field inhomogeneity. T1ρ utilizes a spin-lock pulse to decrease the effect of unwanted relaxation. The objective of this study was to study T1ρ as compared to T1, ECV, and LGE in HCM patients. METHODS: HCM patients were recruited as part of the Novel Markers of Prognosis in Hypertrophic Cardiomyopathy study, and healthy controls were matched for comparison. In addition to cardiac functional imaging, subjects underwent T1 and T1ρ cardiovascular magnetic resonance imaging at short-axis positions at 1.5T. Subjects received gadolinium and underwent LGE imaging 15-20 min after injection covering the entire heart. Corresponding basal and mid short axis LGE slices were selected for comparison with T1 and T1ρ. Full-width half-maximum thresholding was used to determine the percent enhancement area in each LGE-positive slice by LGE, T1, and T1ρ. Two clinicians independently reviewed LGE images for presence or absence of enhancement. If in agreement, the image was labeled positive (LGE + +) or negative (LGE --); otherwise, the image was labeled equivocal (LGE + -). RESULTS: In 40 HCM patients and 10 controls, T1 percent enhancement area (Spearman's rho = 0.61, p < 1e-5) and T1ρ percent enhancement area (Spearman's rho = 0.48, p < 0.001e-3) correlated with LGE percent enhancement area. T1 and T1ρ percent enhancement areas were also correlated (Spearman's rho = 0.28, p = 0.047). For both T1 and T1ρ, HCM patients demonstrated significantly longer relaxation times compared to controls in each LGE category (p < 0.001 for all). HCM patients also showed significantly higher ECV compared to controls in each LGE category (p < 0.01 for all), and LGE -- slices had lower ECV than LGE + + (p = 0.01). CONCLUSIONS: Hyperenhancement areas as measured by T1ρ and LGE are moderately correlated. T1, T1ρ, and ECV were elevated in HCM patients compared to controls, irrespective of the presence of LGE. These findings warrant additional studies to investigate the prognostic utility of T1ρ imaging in the evaluation of HCM patients.

MRI evaluation of cerebrovascular reactivity in obstructive sleep apnea.

Obstructive sleep apnea (OSA) is characterized by intermittent obstruction of the airways during sleep. Cerebrovascular reactivity (CVR) is an index of cerebral vessels' ability to respond to a vasoactive stimulus, such as increased CO2. We hypothesized that OSA alters CVR, expressed as a breath-hold index (BHI) defined as the rate of change in CBF or BOLD signal during a controlled breath-hold stimulus mimicking spontaneous apneas by being both hypercapnic and hypoxic. In 37 OSA and 23 matched non sleep apnea (NSA) subjects, we obtained high temporal resolution CBF and BOLD MRI data before, during, and between five consecutive BH stimuli of 24 s, each averaged to yield a single BHI value. Greater BHI was observed in OSA relative to NSA as derived from whole-brain CBF (78.6 ± 29.6 vs. 60.0 ± 20.0 mL/min2/100 g, P = 0.010) as well as from flow velocity in the superior sagittal sinus (0.48 ± 0.18 vs. 0.36 ± 0.10 cm/s2, P = 0.014). Similarly, BOLD-based BHI was greater in OSA in whole brain (0.19 ± 0.08 vs. 0.15 ± 0.03%/s, P = 0.009), gray matter (0.22 ± 0.09 vs. 0.17 ± 0.03%/s, P = 0.011), and white matter (0.14 ± 0.06 vs. 0.10 ± 0.02%/s, P = 0.010). The greater CVR is not currently understood but may represent a compensatory mechanism of the brain to maintain oxygen supply during intermittent apneas.

Calibrated fMRI for dynamic mapping of CMRO2 responses using MR-based measurements of whole-brain venous oxygen saturation.

Functional MRI (fMRI) can identify active foci in response to stimuli through BOLD signal fluctuations, which represent a complex interplay between blood flow and cerebral metabolic rate of oxygen (CMRO2) changes. Calibrated fMRI can disentangle the underlying contributions, allowing quantification of the CMRO2 response. Here, whole-brain venous oxygen saturation (Yv) was computed alongside ASL-measured CBF and BOLD-weighted data to derive the calibration constant, M, using the proposed Yv-based calibration. Data were collected from 10 subjects at 3T with a three-part interleaved sequence comprising background-suppressed 3D-pCASL, 2D BOLD-weighted, and single-slice dual-echo GRE (to measure Yv via susceptometry-based oximetry) acquisitions while subjects breathed normocapnic/normoxic, hyperoxic, and hypercapnic gases, and during a motor task. M was computed via Yv-based calibration from both hypercapnia and hyperoxia stimulus data, and results were compared to conventional hypercapnia or hyperoxia calibration methods. Mean M in gray matter did not significantly differ between calibration methods, ranging from 8.5 ± 2.8% (conventional hyperoxia calibration) to 11.7 ± 4.5% (Yv-based calibration in response to hyperoxia), with hypercapnia-based M values between (p = 0.56). Relative CMRO2 changes from finger tapping were computed from each M map. CMRO2 increased by ∼20% in the motor cortex, and good agreement was observed between the conventional and proposed calibration methods.

High-speed whole-brain oximetry by golden-angle radial MRI.

PURPOSE: To determine whole-brain cerebral metabolic rate of oxygen (CMRO2 ), an improved imaging approach, based on radial encoding, termed radial OxFlow (rOxFlow), was developed to simultaneously quantify draining vein venous oxygen saturation (SvO2 ) and total cerebral blood flow (tCBF). METHODS: To evaluate the efficiency and precision of the rOxFlow sequence, 10 subjects were studied during a paradigm of repeated breath-holds with both rOxFlow and Cartesian OxFlow (cOxFlow) sequences. CMRO2 was calculated at baseline from OxFlow-measured data assuming an arterial O2 saturation of 97%, and the SvO2 and tCBF breath-hold responses were quantified. RESULTS: Average neurometabolic-vascular parameters across the 10 subjects for cOxFlow and rOxFlow were, respectively: SvO2 (%) baseline: 64.6 ± 8.0 versus 64.2 ± 6.6; SvO2 peak: 70.5 ± 8.5 versus 72.6 ± 5.4; tCBF (mL/min/100 g) baseline: 39.2 ± 3.8 versus 40.6 ± 8.0; tCBF peak: 53.2 ± 5.1 versus 56.1 ± 11.7; CMRO2 (µmol O2 /min/100 g) baseline: 111.5 ± 26.8 versus 120.1 ± 19.6. The above measures were not significantly different between sequences (P > 0.05). CONCLUSION: There was good agreement between the two methods in terms of the physiological responses measured. Comparing the two, rOxFlow provided higher temporal resolution and greater flexibility for reconstruction while maintaining high SNR. Magn Reson Med 79:217-223, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Simultaneous measurement of macro- and microvascular blood flow and oxygen saturation for quantification of muscle oxygen consumption.

PURPOSE: To investigate the relationship between blood flow and oxygen consumption in skeletal muscle, a technique called "Velocity and Perfusion, Intravascular Venous Oxygen saturation and T2*" (vPIVOT) is presented. vPIVOT allows the quantification of feeding artery blood flow velocity, perfusion, draining vein oxygen saturation, and muscle T2*, all at 4-s temporal resolution. Together, the measurement of blood flow and oxygen extraction can yield muscle oxygen consumption ( V˙O2) via the Fick principle. METHODS: In five subjects, vPIVOT-derived results were compared with those obtained from stand-alone sequences during separate ischemia-reperfusion paradigms to investigate the presence of measurement bias. Subsequently, in 10 subjects, vPIVOT was applied to assess muscle hemodynamics and V˙O2 following a bout of dynamic plantar flexion contractions. RESULTS: From the ischemia-reperfusion paradigm, no significant differences were observed between data from vPIVOT and comparison sequences. After exercise, the macrovascular flow response reached a maximum 8 ± 3 s after relaxation; however, perfusion in the gastrocnemius muscle continued to rise for 101 ± 53 s. Peak V˙O2 calculated based on mass-normalized arterial blood flow or perfusion was 15.2 ± 6.7 mL O2 /min/100 g or 6.0 ± 1.9 mL O2 /min/100 g, respectively. CONCLUSIONS: vPIVOT is a new method to measure blood flow and oxygen saturation, and therefore to quantify muscle oxygen consumption. Magn Reson Med 79:846-855, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

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 © 2016 John Wiley & Sons, Ltd.

Calibrated bold fMRI with an optimized ASL-BOLD dual-acquisition sequence.

Calibrated fMRI techniques estimate task-induced changes in the cerebral metabolic rate of oxygen (CMRO2) based on simultaneous measurements of cerebral blood flow (CBF) and blood-oxygen-level-dependent (BOLD) signal changes evoked by stimulation. To determine the calibration factor M (corresponding to the maximum possible BOLD signal increase), BOLD signal and CBF are measured in response to a gas breathing challenge (usually CO2 or O2). Here we describe an ASL dual-acquisition sequence that combines a background-suppressed 3D-GRASE readout with 2D multi-slice EPI. The concatenation of these two imaging sequences allowed separate optimization of the acquisition for CBF and BOLD data. The dual-acquisition sequence was validated by comparison to an ASL sequence with a dual-echo EPI readout, using a visual fMRI paradigm. Results showed a 3-fold increase in temporal signal-to-noise ratio (tSNR) of the ASL time-series data while BOLD tSNR was similar to that obtained with the dual-echo sequence. The longer TR of the proposed dual-acquisition sequence, however, resulted in slightly lower T-scores (by 30%) in the BOLD activation maps. Further, the potential of the dual-acquisition sequence for M-mapping on the basis of a hypercapnia gas breathing challenge and for quantification of CMRO2 changes in response to a motor activation task was assessed. In five subjects, an average gray matter M-value of 8.71±1.03 and fractional changes of CMRO2 of 12.5±5% were found. The new sequence remedies the deficiencies of prior combined BOLD-ASL acquisition strategies by substantially enhancing perfusion tSNR, which is essential for accurate BOLD calibration.

Measurement of skeletal muscle perfusion dynamics with pseudo-continuous arterial spin labeling (pCASL): Assessment of relative labeling efficiency at rest and during hyperemia, and comparison to pulsed arterial spin labeling (PASL).

PURPOSE: To compare calf skeletal muscle perfusion measured with pulsed arterial spin labeling (PASL) and pseudo-continuous arterial spin labeling (pCASL) methods, and to assess the variability of pCASL labeling efficiency in the popliteal artery throughout an ischemia-reperfusion paradigm. MATERIALS AND METHODS: At 3T, relative pCASL labeling efficiency was experimentally assessed in five subjects by measuring the signal intensity of blood in the popliteal artery just distal to the labeling plane immediately following pCASL labeling or control preparation pulses, or without any preparation pulses throughout separate ischemia-reperfusion paradigms. The relative label and control efficiencies were determined during baseline, hyperemia, and recovery. In a separate cohort of 10 subjects, pCASL and PASL sequences were used to measure reactive hyperemia perfusion dynamics. RESULTS: Calculated pCASL labeling and control efficiencies did not differ significantly between baseline and hyperemia or between hyperemia and recovery periods. Relative to the average baseline, pCASL label efficiency was 2 ± 9% lower during hyperemia. Perfusion dynamics measured with pCASL and PASL did not differ significantly (P > 0.05). Average leg muscle peak perfusion was 47 ± 20 mL/min/100g or 50 ± 12 mL/min/100g, and time to peak perfusion was 25 ± 3 seconds and 25 ± 7 seconds from pCASL and PASL data, respectively. Differences of further metrics parameterizing the perfusion time course were not significant between pCASL and PASL measurements (P > 0.05). CONCLUSION: No change in pCASL labeling efficiency was detected despite the almost 10-fold increase in average blood flow velocity in the popliteal artery. pCASL and PASL provide precise and consistent measurement of skeletal muscle reactive hyperemia perfusion dynamics. J. MAGN. RESON. IMAGING 2016;44:929-939.

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.

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 developedOxFlowMRI 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/m(2),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, CMRO2decreased 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.

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 (SvO2) 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 method's 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-OxFlow's 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.

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.

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.

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.

Time-resolved MRI oximetry for quantifying CMRO(2) and vascular reactivity.

This brief review of magnetic resonance susceptometry summarizes the methods conceived in the authors' laboratory during the past several years. This article shows how venous oxygen saturation is quantified in large draining veins by field mapping and how this information, in concert with simultaneous measurement of cerebral blood flow, yields cerebral metabolic rate of oxygen, the brain's rate of oxygen consumption. The accuracy of this model-based approach in which the blood vessel is approximated as a long, straight cylinder, for which an analytical solution for the induced field exists, is discussed. It is shown that the approach is remarkably robust, allowing for time-resolved quantification of whole-brain metabolism at rest and in response to stimuli, thereby providing detailed information on cerebral physiology in health and disease not previously amenable by noninvasive methods.

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

BACKGROUND: The 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*. METHODS: Perfusion, 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. RESULTS: Comparison 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. CONCLUSION: Simultaneous 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.

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.

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

BACKGROUND: The 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 RESULTS: The 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). CONCLUSION: The 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.

High-resolution imaging and antitumor effects of GFP(+) bone marrow-derived cells homing to syngeneic mouse colon tumors.

Bone marrow-derived cells (BMDCs) participate in the growth and spread of tumors of the breast, brain, lung, and stomach. To date, there are limited reports of bone marrow involvement in colon cancer pathogenesis, but such findings would have the potential to generate novel treatments for colon cancer patients. We have established a mouse model for imaging BMDCs from whole tumor to single-cell resolution, whereby the bone marrow of lethally irradiated host animals is reconstituted with EGFP-expressing bone marrow cells from matched TgActb(EGFP) donors. The BM transplants yield mice with fluorescently labeled bone marrow, and so BMDCs can subsequently be monitored within a tumor through optical imaging. Successful BM reconstitution was confirmed at 8 weeks after transplantation, when surviving BALB/c mice were injected with CT26 mouse colon cancer cells. We find that up to 45% of cells dissociated from the tumors are GFP(+) and approximately 50% of Lin(+), CD11b(+), and CD3(+) cells express high levels of GFP. Notably, tumor growth is reduced in BM transplanted animals, compared with untransplanted host mice or EGFP-expressing BM donor mice. A needed next step is to separate the molecular and cellular (eg, T cells, NK cells, macrophages) bases of the antitumor effect of the BMDCs from any protumorigenic effect that could be subverted for therapeutic gain.