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.
The effects of e-cigarette (e-cig) aerosol inhalation by nonsmokers have not been examined to date. The present study was designed to evaluate the acute response to aerosol inhalation of ...non-nicotinized e-cigarettes in terms of oxidative stress and indices of endothelial activation in human pulmonary microvascular endothelial cells (HPMVEC). Ten smoking-naïve healthy subjects (mean age ± SD = 28.7 ± 5.5 yr) were subjected to an e-cig challenge, following which their serum was monitored for markers of inflammation C-reactive protein (CRP) and soluble intercellular adhesion molecule (sICAM) and nitric oxide metabolites (NOx). The oxidative stress and inflammation burden of the circulating serum on the vascular network was also assessed by measuring reactive oxygen species (ROS) production and induction of ICAM-1 expression on HPMVEC. Our results show that serum indices of oxidative stress and inflammation increased significantly (
< 0.05 as compared with baseline), reaching a peak at approximately 1-2 h post-e-cig aerosol inhalation and returning to baseline levels at 6 h. The circulatory burden of the serum (ICAM-1 and ROS) increased significantly at 2 h and returned to baseline values 6 h post-e-cig challenge. ROS production by HPMVEC was found to occur via activation of the NADPH oxidase 2 (NOX2) pathways. These findings suggest that even in the absence of nicotine, acute e-cig aerosol inhalation leads to a transient increase in oxidative stress and inflammation. This can adversely affect the vascular endothelial network by promoting oxidative stress and immune cell adhesion. Thus e-cig inhalation has the potential to drive the onset of vascular pathologies.
The endothelium regulates and mediates vascular homeostasis, allowing for dynamic changes of blood flow in response to mechanical and chemical stimuli. Endothelial dysfunction underlies many diseases ...and is purported to be the earliest pathologic change in the progression of atherosclerotic disease. Peripheral vascular function can be interrogated by measuring the response kinetics following induced ischemia or exercise. In the presence of endothelial dysfunction, there is a blunting and delay of the hyperemic response, which can be measured non-invasively using a variety of quantitative magnetic resonance imaging (MRI) methods. In this review, we summarize recent developments in non-contrast, proton MRI for dynamic quantification of blood flow and oxygenation. Methodologic description is provided for: blood oxygenation-level dependent (BOLD) signal that reflect combined effect of blood flow and capillary bed oxygen content; arterial spin labeling (ASL) for quantification of regional perfusion; phase contrast (PC) to quantify arterial flow waveforms and macrovascular blood flow velocity and rate; high-resolution MRI for luminal flow-mediated dilation; and dynamic MR oximetry to quantify oxygen saturation. Overall, results suggest that these dynamic and quantitative MRI methods can detect endothelial dysfunction both in the presence of overt cardiovascular disease (such as in patients with peripheral artery disease), as well as in sub-clinical settings (i.e., in chronic smokers, non-smokers exposed to e-cigarette aerosol, and as a function of age). Thus far, these tools have been relegated to the realm of research, used as biomarkers of disease progression and therapeutic response. With proper validation, MRI-measures of vascular function may ultimately be used to complement the standard clinical workup, providing additional insight into the optimal treatment strategy and evaluation of treatment efficacy.
During the early stages of diabetes, kidney oxygen utilization increases. The mismatch between oxygen demand and supply contributes to tissue hypoxia, a key driver of chronic kidney disease. Thus, ...whole‐organ renal metabolic rate of oxygen (rMRO2) is a potentially valuable biomarker of kidney function. The key parameters required to determine rMRO2 include the renal blood flow rate (RBF) in the feeding artery and oxygen saturation in the draining renal vein (SvO2). However, there is currently no noninvasive method to quantify rMRO2 in absolute physiologic units. Here, a new MRI pulse sequence, Kidney Metabolism of Oxygen via T2 and Interleaved Velocity Encoding (K‐MOTIVE), is described, along with evaluation of its performance in the human kidney in vivo. K‐MOTIVE interleaves a phase‐contrast module before a background‐suppressed T2‐prepared balanced steady‐state‐free‐precession (bSSFP) readout to measure RBF and SvO2 in a single breath‐hold period of 22 s, yielding rMRO2 via Fick's principle. Variants of K‐MOTIVE to evaluate alternative bSSFP readout strategies were studied. Kidney mass was manually determined from multislice gradient recalled echo images. Healthy subjects were recruited to quantify rMRO2 of the left kidney at 3‐T field strength (N = 15). Assessments of repeat reproducibility and comparisons with individual measurements of RBF and SvO2 were performed, and the method's sensitivity was evaluated with a high‐protein meal challenge (N = 8). K‐MOTIVE yielded the following metabolic parameters: T2 = 157 ± 19 ms; SvO2 = 92% ± 6%; RBF = 400 ± 110 mL/min; and rMRO2 = 114 ± 117(μmol O2/min)/100 g tissue. Reproducibility studies of T2 and RBF (parameters directly measured by K‐MOTIVE) resulted in coefficients of variation less than 10% and intraclass correlation coefficients more than 0.75. The high‐protein meal elicited an increase in rMRO2, which was corroborated by serum biomarkers. The K‐MOTIVE sequence measures SvO2 and RBF, the parameters necessary to quantify whole‐organ rMRO2, in a single breath‐hold. The present work demonstrates that rMRO2 quantification is feasible with good reproducibility. rMRO2 is a potentially valuable physiological biomarker.
A new pulse sequence named Kidney Metabolism of Oxygen via T2 and Interleaved Velocity Encoding (K‐MOTIVE) is proposed to quantify renal metabolic rate of oxygen (rMRO2). K‐MOTIVE simultaneously measures venous oxygen saturation (SvO2) and blood flow rate. This work demonstrates the feasibility of rMRO2 quantification for the first time.
Purpose
Renal metabolic rate of oxygen (rMRO2) is a potentially important biomarker of kidney function. The key parameters for rMRO2 quantification include blood flow rate (BFR) and venous oxygen ...saturation (SvO2) in a draining vessel. Previous approaches to quantify renal metabolism have focused on the single organ. Here, both kidneys are considered as one unit to quantify bilateral rMRO2. A pulse sequence to facilitate bilateral rMRO2 quantification is introduced.
Methods
To quantify bilateral rMRO2, measurements of BFR and SvO2 are made along the inferior vena cava (IVC) at suprarenal and infrarenal locations. From the continuity equation, these four parameters can be related to derive an expression for bilateral rMRO2. The recently reported K‐MOTIVE pulse sequence was implemented at four locations: left kidney, right kidney, suprarenal IVC, and infrarenal IVC. A dual‐band variant of K‐MOTIVE (db‐K‐MOTIVE) was developed by incorporating simultaneous‐multi‐slice imaging principles. The sequence simultaneously measures BFR and SvO2 at suprarenal and infrarenal locations in a single pass of 21 s, yielding bilateral rMRO2.
Results
SvO2 and BFR are higher in suprarenal versus infrarenal IVC, and the renal veins are highly oxygenated (SvO2 >90%). Bilateral rMRO2 quantified in 10 healthy subjects (8 M, 30 ± 8 y) was found to be 291 ± 247 and 349 ± 300 (μmolO2/min)/100 g, derived from K‐MOTIVE and db‐K‐MOTIVE, respectively. In comparison, total rMRO2 from combining left and right was 329 ± 273 (μmolO2/min)/100 g.
Conclusion
The present work demonstrates that bilateral rMRO2 quantification is feasible with fair reproducibility and physiological plausibility. The indirect method is a promising approach to compute bilateral rMRO2 when individual rMRO2 quantification is difficult.
Objective
Neurovascular compliance (NVC) is the change in the brain’s arterial tree blood volume, Δ
V
, divided by the change in intra-vascular blood pressure, Δ
P
, during the cardiac cycle. The ...primary aim of this work was to evaluate the performance of MRI measurement of NVC obtained from time-resolved measurements of internal carotid artery (ICA) and vertebral artery (VA) flow rates. A secondary aim was to explore whether NVC could be estimated from common carotid (CCA) flow in conjunction with prior knowledge of mean ICA and VA fractional flow rates, given the small cross-section of ICA and VA in some populations, in particular small children.
Methods
Δ
V
was quantified from the blood flow rate measured at the ICA and VA for actual NVC derivation. It was further estimated from individually measured CCA flow rate and mean flow fractions ICA/CCA and VA/CCA (which could alternatively be obtained from literature data), to yield estimated NVC. Time-resolved blood flow rate in CCA, ICA and VA was obtained via retrospectively-gated 2D PC-MRI at 1.5 T in healthy subjects (N = 16, 8 women, mean age 36
±
13 years). Δ
P
was determined via a brachial pressure measurement.
Results
Actual and estimated mean NVC were 27 ± 15 and 38 ± 15 μL/mmHg, respectively, and the two measurements were strongly correlated (r = 0.80;
p
= 0.0002) with test–retest intra-class correlation coefficients of 0.964 and 0.899.
Conclusion
Both methods yielded excellent retest precision. In spite of a large bias, actual and estimated NVC were strongly correlated.
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.
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