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 (S_vO₂) 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.     

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 (S_vO₂) 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 S_vO₂ 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 S_vO₂ 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 S_vO₂ and tCBF upon recovery from hypercapnia in six subjects.     

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.     

Cerebral blood flow, cerebrovascular resistance and cerebral metabolic rate of oxygen in severe arterial hypoxia in dogs

Cerebral blood flow and cerebral oxygen uptake were studied during severe arterial hypoxia in anesthetized dogs. It was shown that the hypoxic vasodilatation in the brain reaches a limit at an arterial oxygen saturation at about 25% and that this vasodilatation is less than that which may be induced by hypercapnia. A further deepening of the arterial hypoxia at a maintained cerebral perfusion pressure is combined with a continuous decrease in cerebral venous oxygen tension and a reduced oxygen uptake.     

Effect of age and vascular anatomy on blood flow in major cerebral vessels

Measurement of volume flow rates in major cerebral vessels can be used to evaluate the hemodynamic effects of cerebrovascular disease. However, both age and vascular anatomy can affect flow rates independent of disease. We prospectively evaluated 325 healthy adult volunteers using phase contrast quantitative magnetic resonance angiography to characterize these effects on cerebral vessel flow rates and establish clinically useful normative reference values. Flows were measured in the major intracranial and extracranial vessels. The cohort ranged from 18 to 84 years old, with 157 (48%) females. All individual vessel flows and total cerebral blood flow (TCBF) declined with age, at 2.6 mL/minute per year for TCBF. Basilar artery (BA) flow was significantly decreased in individuals with one or both fetal posterior cerebral arteries (PCAs). Internal carotid artery flows were significantly higher with a fetal PCA and decreased with a hypoplastic anterior cerebral artery. Indexing vessel flows to TCBF neutralized the age effect, but anatomic variations continued to impact indexed flow in the BA and internal carotid artery. Variability in normative flow ranges were reduced in distal vessels and by examining regional flows. Cerebral vessel flows are affected by age and cerebrovascular anatomy, which has important implications for interpretation of flows in the disease state.     

The contribution of arterial blood gases in cerebral blood flow regulation and fuel utilization in man at high altitude

The effects of partial acclimatization to high altitude (HA; 5,050 m) on cerebral metabolism and cerebrovascular function have not been characterized. We hypothesized (1) increased cerebrovascular reactivity (CVR) at HA; and (2) that CO₂ would affect cerebral metabolism more than hypoxia. PaO₂ and PaCO₂ were manipulated at sea level (SL) to simulate HA exposure, and at HA, SL blood gases were simulated; CVR was assessed at both altitudes. Arterial–jugular venous differences were measured to calculate cerebral metabolic rates and cerebral blood flow (CBF). We observed that (1) partial acclimatization yields a steeper CO₂-H⁺ relation in both arterial and jugular venous blood; yet (2) CVR did not change, despite (3) mean arterial pressure (MAP)-CO₂ reactivity being doubled at HA, thus indicating effective cerebral autoregulation. (4) At SL hypoxia increased CBF, and restoration of oxygen at HA reduced CBF, but neither had any effect on cerebral metabolism. Acclimatization resets the cerebrovasculature to chronic hypocapnia.     

A novel approach to measure local cerebral haematocrit using MRI

The percentage blood volume occupied by red blood cells is known as haematocrit. While it is straightforward to measure haematocrit in large arteries, it is very challenging to do it in microvasculature (cerebral haematocrit). Currently, this can only be done using invasive methods (e.g. PET), but their use is very limited. Local variations in cerebral haematocrit have been reported in various brain abnormalities (e.g. stroke, tumours). We propose a new approach to image cerebral haematocrit using MRI, which relies on combining data from two measurements: one that provides haematocrit-weighted and other one haematocrit-independent values of the same parameter, thus providing an easily obtainable measurement of this important physiological parameter. Four different implementations are described, with one illustrated as proof-of-concept using data from healthy subjects. Cerebral haematocrit measurements were found to be in general agreement with literature values from invasive techniques (e.g. cerebral/arterial ratios of 0.88 and 0.86 for sub-cortical and cortical regions), and showed good test–retest reproducibility (e.g. coefficient-of-variation: 15% and 13% for those regions). The method was also able to detect statistically significant haematocrit gender differences in cortical regions (p < 0.01). The proposed MRI technique should have important applications in various neurological diseases, such as in stroke and brain tumours.     

Absolute arterial cerebral blood volume quantification using inflow vascular-space-occupancy with dynamic subtraction magnetic resonance imaging

In patients with steno-occlusive disease of the internal carotid artery (ICA), cerebral blood flow may be maintained by autoregulatory increases in arterial cerebral blood volume (aCBV). Therefore, characterizing aCBV may be useful for understanding hemodynamic compensation strategies. A new ‘inflow vascular-space-occupancy with dynamic subtraction (iVASO-DS)'' MRI approach is presented where aCBV (mL blood/100 mL parenchyma) is quantified without contrast agents using the difference between images with and without inflowing blood water signal. The iVASO-DS contrast mechanism is investigated (3.0 T, spatial resolution=2.4 × 2.4 × 5 mm³) in healthy volunteers (n=8; age=29±5 years), and patients with mild (n=7; age=72±8 years) and severe (n=10; age=73±8 years) ICA stenoses. aCBV was quantified in right and left hemispheres in controls, and, alongside industry standard dynamic susceptibility contrast (DSC), contralateral (cont), and ipsilateral (ips) to maximum stenosis in patients. iVASO contrast significantly correlated (R=0.67, P<0.01) with DSC-CBV after accounting for transit time discrepancies. Gray matter aCBV (mL/100 mL) was 1.60±0.10 (right) versus 1.61±0.20 (left) in controls, 1.59±0.38 (cont) and 1.65±0.37 (ips) in mild stenosis patients, and 1.72±0.18 (cont) and 1.58±0.20 (ips) in severe stenosis patients. aCBV was asymmetric (P<0.01) in 41% of patients whereas no asymmetry was found in any control. The potential of iVASO-DS for autoregulation studies is discussed in the context of existing hemodynamic literature.     

Cerebral blood flow quantification using vessel-encoded arterial spin labeling

Arterial spin labeling (ASL) techniques are gaining popularity for visualizing and quantifying cerebral blood flow (CBF) in a range of patient groups. However, most ASL methods lack vessel-selective information, which is important for the assessment of collateral flow and the arterial supply to lesions. In this study, we explored the use of vessel-encoded pseudocontinuous ASL (VEPCASL) with multiple postlabeling delays to obtain individual quantitative CBF and bolus arrival time maps for each of the four main brain-feeding arteries and compared the results against those obtained with conventional pseudocontinuous ASL (PCASL) using matched scan time. Simulations showed that PCASL systematically underestimated CBF by up to 37% in voxels supplied by two arteries, whereas VEPCASL maintained CBF accuracy since each vascular component is treated separately. Experimental results in healthy volunteers showed that there is no systematic bias in the CBF estimates produced by VEPCASL and that the signal-to-noise ratio of the two techniques is comparable. Although more complex acquisition and image processing is required and the potential for motion sensitivity is increased, VEPCASL provides comparable data to PCASL but with the added benefit of vessel-selective information. This could lead to more accurate CBF estimates in patients with a significant collateral flow.     

Physiological origin for the BOLD poststimulus undershoot in human brain: vascular compliance versus oxygen metabolism

The poststimulus blood oxygenation level-dependent (BOLD) undershoot has been attributed to two main plausible origins: delayed vascular compliance based on delayed cerebral blood volume (CBV) recovery and a sustained increased oxygen metabolism after stimulus cessation. To investigate these contributions, multimodal functional magnetic resonance imaging was employed to monitor responses of BOLD, cerebral blood flow (CBF), total CBV, and arterial CBV (CBV_a) in human visual cortex after brief breath hold and visual stimulation. In visual experiments, after stimulus cessation, CBV_a was restored to baseline in 7.9±3.4 seconds, and CBF and CBV in 14.8±5.0 seconds and 16.1±5.8 seconds, respectively, all significantly faster than BOLD signal recovery after undershoot (28.1±5.5 seconds). During the BOLD undershoot, postarterial CBV (CBV_pa, capillaries and venules) was slightly elevated (2.4±1.8%), and cerebral metabolic rate of oxygen (CMRO₂) was above baseline (10.6±7.4%). Following breath hold, however, CBF, CBV, CBV_a and BOLD signals all returned to baseline in ∼20 seconds. No significant BOLD undershoot, and residual CBV_pa dilation were observed, and CMRO₂ did not substantially differ from baseline. These data suggest that both delayed CBV_pa recovery and enduring increased oxidative metabolism impact the BOLD undershoot. Using a biophysical model, their relative contributions were estimated to be 19.7±15.9% and 78.7±18.6%, respectively.     

Support vector machine learning‐based cerebral blood flow quantification for arterial spin labeling MRI

Purpose : To develop a multivariate machine learning classification‐based cerebral blood flow (CBF) quantification method for arterial spin labeling (ASL) perfusion MRI. Methods : The label and control images of ASL MRI were separated using a machine‐learning algorithm, the support vector machine (SVM). The perfusion‐weighted image was subsequently extracted from the multivariate (all voxels) SVM classifier. Using the same pre‐processing steps, the proposed method was compared with standard ASL CBF quantification method using synthetic data and in‐vivo ASL images. Results : As compared with the conventional univariate approach, the proposed ASL CBF quantification method significantly improved spatial signal‐to‐noise‐ratio (SNR) and image appearance of ASL CBF images. Conclusion : the multivariate machine learning‐based classification is useful for ASL CBF quantification. Hum Brain Mapp 35:2869–2875, 2014. © 2013 Wiley Periodicals, Inc.     

A brief report on MRI investigation of experimental traumatic brain injury

Traumatic brain injury is a major cause of death and disability. This is a brief report based on a symposium presentation to the2014 Chinese Neurotrauma Association Meeting in San Francisco, USA. It covers the work from our laboratory in applying multimodal MRI to study experimental traumatic brain injury in rats with comparisons made to behavioral tests and histology. MRI protocols include structural, perfusion, manganese-enhanced, diffusion-tensor MRI, and MRI of blood-brain barrier integrity and cerebrovascular reactivity.     

急性重症脑梗死患者脑血流灌注状态及其与预后的关系

目的 探讨急性重症脑梗死患者脑血流灌注状态及其与预后的关系.方法 回顾性分析10例急性重症脑梗死患者的临床及MR资料.结果 本组患者患侧局部脑血流量(rCBF)和局部脑血容量(rCBV)明显下降9例(90%),与对侧脑组织相比分别降低64.1%和49.7%,两侧比较有统计学意义(P=0.001;P=0.01);MRA显示本组10例患者(100%)患侧大血管(颈内动脉或大脑中动脉)均闭塞,同时合并对侧大血管狭窄或闭塞7例(70%).死亡2例,重残8例.结论 急性重症脑梗死患者的脑血流灌注明显降低,预后很差.     

The bidirectional association between reduced cerebral blood flow and brain atrophy in the general population

The question remains whether reduced cerebral blood flow (CBF) leads to brain atrophy or vice versa. We studied the longitudinal relation between CBF and brain volume in a community-dwelling population. In the Rotterdam Study, 3011 participants (mean age 59.6 years (s.d. 8.0)) underwent repeat brain magnetic resonance imaging to quantify brain volume and CBF at two time points. Adjusted linear regression models were used to investigate the bidirectional relation between CBF and brain volume. We found that smaller brain volume at baseline was associated with a steeper decrease in CBF in the whole population (standardized change per s.d. increase of total brain volume (TBV)=0.296 (95% confidence interval (CI) 0.200; 0.393)). Only in persons aged ⩾65 years, a lower CBF at baseline was associated with steeper decline of TBV (standardized change per s.d. increase of CBF=0.003 (95% CI −0.004; 0.010) in the whole population and 0.020 (95% CI 0.004; 0.036) in those aged ⩾65 years of age). Our results indicate that brain atrophy causes CBF to decrease over time, rather than vice versa. Only in persons aged >65 years of age did we find lower CBF to also relate to brain atrophy.     

Cerebral blood flow and metabolism following subarachnoid haemorrhage: cerebral oxygen uptake and global blood flow during the acute period in patients with SAH

Forty-eight patients with subarachnoid haemorrhage were studied with repeated rCBF and CMRO2 measurements. Cortical rCBF was measured using xenon-inhalation technique. CMRO2 was calculated as AVDO2 x CBF. When first studied the 29 conscious patients showed relative hyperaemia with CBF at 50 ml and reduced CMRO2 at 2.17 ml. In the following week CBF decreased to 41. CMRO2 remained reduced and constant. The 19 unconscious patients showed initially pronounced reduction in CMRO2 to 1.26, followed by gradual increase to 1.73 in 4-5 days. Simultaneously CBF increased from 18 ml to slightly above 30 ml. In the conscious patients the early reduction in CMRO2 and the concomitant luxury perfusion may be explained by global ischaemia because of very high ICP at the time of the haemorrhage. The reduced CBF in the unconscious group could be due to increased ICP, as ventricular drainage increased CBF to levels of relative hyperaemia as demonstrated in one case. As no decrease in CMRO2 was seen during the first 2 weeks, it is suggested that ischaemia at the time of aneurysm rupture is the most important single factor in reduction of global CMRO2.     

Determination of the rate of cerebral oxygen consumption and regional cerebral blood flow by non-invasive 17O in vivo NMR spectroscopy and magnetic resonance imaging: Part 1. Theory and data analysis methods Daniel Fiat and Seho Kang

Abstract

Theory and novel data analysis methods of 170 inhalation measurements are presented for the calculation of CMR02, regional cerebral blood flow (rCBF), the reflow (R), the arterial venous difference (AVD) and the partition coefficient (X). Several of the methods proposed for the determination of CMR02 do not require measurements of regional cerebral blood flow and H2170 arterial concentration. All methods'of analysis are based on the Kety-Schmidt approach. [Neurol Res 1992; 14: 303-311]     

Regional cerebral oxygen utilization and blood flow in normal man using oxygen-15 and positron emission tomography

Quantitative determination of regional cerebral blood flow (rCBF), regional cerebral oxygen utilization (rCMRO₂) and regional oxygen extraction ratio (rOER) was performed in 11 normal volunteers by an oxygen-15 inhalation method and positron emission tomography.
Regional values comparable with figures from the literature have been obtained.
This non-invasive approach offers the possibility of a simultaneous quantitative evaluation of these physiological parameters in health and disease.     

Measurement of cerebral blood flow responses to the thigh cuff maneuver: a comparison of TCD with a novel MRI method

Cerebral autoregulation (CA) describes the mechanism responsible for maintaining cerebral blood flow (CBF) relatively constant, despite changes in mean arterial blood pressure (ABP). This paper introduces a novel method for assessing CA using magnetic resonance imaging (MRI). Images are rapidly and repeatedly acquired using a gradient-echo echo-planar imaging pulse sequence for a period of 4 minutes, during which a transient decrease in ABP is induced by rapid release of bilateral thigh cuffs. The method was validated by comparing the observed MRI signal intensity change with the CBF velocity change in the middle cerebral arteries, as measured by transcranial Doppler (TCD) ultrasound, using a standardized thigh cuff maneuver in both cases. Cross-correlation analysis of the response profiles from the left and right hemispheres showed a greater consistency for MRI measures than for TCD, both for interhemisphere comparisons and for repeated measures. The new MRI method may provide opportunities for assessing regional autoregulatory changes following acute stroke, and in other conditions in which poor autoregulation is implicated.     

History of International Society for Cerebral Blood Flow and Metabolism

Interest in the brain's circulation dates back more than a century and has been steadily growing. Quantitative methods for measurements of cerebral blood flow (CBF) and energy metabolism became available in the middle of the 20th century and gave a new boost to the research. Scientific meetings dealing with CBF and metabolism were arranged, and the fast growing research led to a demand for a specialized journal. In this scientific environment, the International Society for Cerebral Blood Flow and Metabolism (ISCBFM) and its official Journal of Cerebral Metabolism were established in 1981 and has since then been a major success. The development of new brain imaging methods has had a major impact. Regulation of CBF and ischemia has been the main topics at the meetings. A new field of brain mapping research emerged and has now its own society and meetings. Brain emission tomography research has grown within the society and is now an integrated part. The ISCBFM is a sound society, and support of young scientists is among its goals. Several awards have been established. Other activities including summer schools, courses, satellite meetings, and Gordon conferences have contributed to the success of the society and strengthened the research.