Arterial transit time effects in pulsed arterial spin labeling CBF mapping: Insight from a PET and MR study in normal human subjects

Arterial transit time (ATT), a key parameter required to calculate absolute cerebral blood flow in arterial spin labeling (ASL), is subject to much uncertainty. In this study, ASL ATTs were estimated on a per‐voxel basis using data measured by both ASL and positron emission tomography in the same subjects. The mean ATT increased by 260 ± 20 (standard error of the mean) ms when the imaging slab shifted downwards by 54 mm, and increased from 630 ± 30 to 1220 ± 30 ms for the first slice, with an increase of 610 ± 20 ms over a four‐slice slab when the gap between the imaging and labeling slab increased from 20 to 74 mm. When the per‐slice ATTs were employed in ASL cerebral blood flow quantification and the in‐slice ATT variations ignored, regional cerebral blood flow could be significantly different from the positron emission tomography measures. ATT also decreased with focal activation by the same amount for both visual and motor tasks (～80 ms). These results provide a quantitative relationship between ATT and the ASL imaging geometry and yield an assessment of the assumptions commonly used in ASL imaging. These findings should be considered in the interpretation of, and comparisons between, different ASL‐based cerebral blood flow studies. The results also provide spatially specific ATT data that may aid in optimizing the ASL imaging parameters. Magn Reson Med, 2010. © 2009 Wiley‐Liss, Inc.     

Characterization of paramagnetic effects of molecular oxygen on blood oxygenation level‐dependent‐modulated hyperoxic contrast studies of the human brain

In hyperoxic contrast studies modulated by the blood oxygenation level‐dependent effect, it is often assumed that hyperoxia is a purely intravascular, positive contrast agent in T‐weighted images, and the effects that are not due to blood oxygenation level‐dependent contrast are small enough to be ignored. In this study, this assumption is re‐evaluated and non‐blood oxygenation level‐dependent effects in T‐weighted hyperoxic contrast studies of the human brain were characterized. We observed significant negative signal changes in T‐weighted images in the frontal lobes; B₀ maps suggest that this effect was primarily due to increased intravoxel dephasing from increased static field inhomogeneity due to susceptibility changes from oxygen in and around the upper airway. These static field effects were shown to scale with magnetic field strength. Signal changes observed around the brain periphery and in the ventricles suggest the effect of image distortions from oxygen‐induced bulk B₀ shifts, along with a possible contribution from decreased T due to oxygen dissolved in the cerebrospinal fluid. Reducing the concentration of inhaled oxygen was shown to mitigate negative contrast of molecular oxygen due to these effects, while still maintaining sufficient blood oxygenation level‐dependent contrast to produce accurate measurements of cerebral blood volume. Magn Reson Med, 2011. © 2011 Wiley‐Liss, Inc.     

PET measurements of CBF,OEF, and CMRO<Subscript>2</Subscript> without arterial sampling in hyperacute ischemic stroke: Method and error analysis

A method for relative measurement of cerebral blood flow (CBF), oxygen extraction fraction (OEF), and metabolic rate of oxygen (CMRO2) using positron emission tomography (PET) without arterial sampling in patients with hyperacute ischemic stroke was presented. METHODS: The method requires two PET scans, one for H2(15)O injection and one for 15O2 inhalation, and calculates regional CBF, CMRO2, and OEF relative to those at the reference brain region by means of table-lookup method. In this study, we calculated "relative lookup-tables" which relate relative CBF to relative H2(15)O count, relative CMRO2 to relative 15O2 count, and relative OEF to relative 15O2/H2(15)O count. Two assumptions were applied to the lookup-table calculation: 1) In the reference region. CBF and OEF were assumed to be 50.0 ml/min/100 ml and 0.40, respectively, 2) Cerebral blood volume (CBV) was assumed to be constant at 4.0 ml/100 ml over the whole brain. Simulation studies were done to estimate the error of the present method derived from the assumptions. RESULTS: For relative CBF measurements, 20% variation in reference CBF gave about +/- 10% error for measured relative CBF at maximum. Changes in CBV caused relatively large errors in measured OEF and CMRO2 when relative CBF and OEF decreased. Errors for measured relative OEF caused by 50% variation in CBV were within +/- 8% at 0.8 of relative CBF and +/- 12% at 0.4 of relative CBF when relative OEF was greater than 1.0. CONCLUSION: CBV effects caused larger errors in estimated OEF and CMRO2 in the region of the ischemic core with decreasing relative CBF and/or OEF but only slight errors in the region of "misery perfusion" with relative OEF values greater than 1.0. The present method makes PET measurements simpler than with the conventional method and increases understanding of the cerebral circulation and oxygen metabolism in patients with hyperacute stroke of several hours after onset.     

Recommended implementation of arterial spin‐labeled perfusion MRI for clinical applications: A consensus of the ISMRM perfusion study group and the European consortium for ASL in dementia

This review provides a summary statement of recommended implementations of arterial spin labeling (ASL) for clinical applications. It is a consensus of the ISMRM Perfusion Study Group and the European ASL in Dementia consortium, both of whom met to reach this consensus in October 2012 in Amsterdam. Although ASL continues to undergo rapid technical development, we believe that current ASL methods are robust and ready to provide useful clinical information, and that a consensus statement on recommended implementations will help the clinical community to adopt a standardized approach. In this review, we describe the major considerations and trade‐offs in implementing an ASL protocol and provide specific recommendations for a standard approach. Our conclusion is that as an optimal default implementation, we recommend pseudo‐continuous labeling, background suppression, a segmented three‐dimensional readout without vascular crushing gradients, and calculation and presentation of both label/control difference images and cerebral blood flow in absolute units using a simplified model. Magn Reson Med 73:102–116, 2015. © 2014 Wiley Periodicals, Inc.     

Database of normal human cerebral blood flow, cerebral blood volume, cerebral oxygen extraction fraction and cerebral metabolic rate of oxygen measured by positron emission tomography with 15O-labelled carbon dioxide or water, carbon monoxide and oxygen: a multicentre study in Japan

Measurement of cerebral blood flow (CBF), cerebral blood volume (CBV), cerebral oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO₂) by positron emission tomography (PET) with oxygen-15 labelled carbon dioxide (C¹⁵O₂) or ¹⁵O-labelled water (H₂ ¹⁵O), ¹⁵O-labelled carbon monoxide (C¹⁵O) and ¹⁵O-labelled oxygen (¹⁵O₂) is useful for diagnosis and treatment planning in cases of cerebrovascular disease. The measured values theoretically depend on various factors, which may differ between PET centres. This study explored the applicability of a database of ¹⁵O-PET by examining between-centre and within-centre variation in values. Eleven PET centres participated in this multicentre study; seven used the steady-state inhalation method, one used build-up inhalation and three used bolus administration of C¹⁵O₂ (or H₂ ¹⁵O) and ¹⁵O₂. All used C¹⁵O for measurement of CBV. Subjects comprised 70 healthy volunteers (43 men and 27 women; mean age 51.8±15.1 years). Overall mean±SD values for cerebral cortical regions were: CBF=44.4±6.5 ml 100 ml^–1 min^–1; CBV=3.8±0.7 ml 100 ml^–1; OEF=0.44±0.06; CMRO₂=3.3±0.5 ml 100 ml^–1 min^–1. Significant between-centre variation was observed in CBV, OEF and CMRO₂ by one-way analysis of variance. However, the overall inter-individual variation in CBF, CBV, OEF and CMRO₂ was acceptably small. Building a database of normal cerebral haemodynamics obtained by the¹⁵O-PET methods may be practicable.     

Effects of inflow and radiofrequency spoiling on the arterial input function in dynamic contrast‐enhanced MRI: A combined phantom and simulation study

The arterial input function is crucial in pharmacokinetic analysis of dynamic contrast‐enhanced MRI data. Among other artifacts in arterial input function quantification, the blood inflow effect and nonideal radiofrequency spoiling can induce large measurement errors with subsequent reduction of accuracy in the pharmacokinetic parameters. These errors were investigated for a 3D spoiled gradient‐echo sequence using a pulsatile flow phantom and a total of 144 typical imaging settings. In the presence of large inflow effects, results showed poor average accuracy and large spread between imaging settings, when the standard spoiled gradient‐echo signal equation was used in the analysis. For example, one of the investigated inflow conditions resulted in a mean error of about 40% and a spread, given by the coefficient of variation, of 20% for K^trans. Minimizing inflow effects by appropriate slice placement, combined with compensation for nonideal radiofrequency spoiling, significantly improved the results, but they remained poorer than without flow (e.g., 3–4 times larger coefficient of variation for K^trans). It was concluded that the 3D spoiled gradient‐echo sequence is not optimal for accurate arterial input function quantification and that correction for nonideal radiofrequency spoiling in combination with inflow minimizing slice placement should be used to reduce the errors. Magn Reson Med, 2011. © 2011 Wiley‐Liss, Inc.     

No adverse effects of statins on muscle function and health‐related parameters in the elderly: An exercise study

The aim of the present study was to investigate the effects of a repeated bout of eccentric exercise on health‐related parameters and muscle performance on subjects undergoing atorvastatin therapy. Twenty‐eight elderly men participated in the investigation and were assigned either in a control (n = 14) or in a statin therapy group (n = 14). All participants performed two isokinetic eccentric exercise bouts separated by 3 weeks. Muscle damage indices, resting energy expenditure, substrate metabolism, lipid and lipoprotein profile, as well as insulin sensitivity, were evaluated before and after eccentric. No differences in muscle function were observed between the two groups either at rest or after exercise. Eccentric exercise increased resting energy expenditure, increased fat oxidation, improved lipid profile, and increased insulin resistance 2 days after both eccentric exercise bouts. However, these changes appeared to lesser extent after the second bout. No differences were observed in the responses in the health‐related parameters in the control and in the statin therapy group. Eccentric exercise affected similarly the control and the atorvastatin‐treated individuals. The present results indicate that atorvastatin‐treated elderly individuals may participate in various physical activities, even high‐intensity muscle‐damaging activities, without negative impact on muscle function and adaptation.