Measuring the Effects of Remifentanil on Cerebral Blood Flow and Arterial Arrival Time Using 3D Grase MRI with Pulsed Arterial Spin Labelling

The APOE 4 allele is a risk factor for late-life pathological changes that is also associated with anatomical and functional brain changes in middle-aged and elderly healthy subjects. We investigated structural and functional effects of the APOE polymorphism in 18 young healthy APOE 4-carriers and 18 matched noncarriers (age range: 20 -35 years). Brain activity was studied both at rest and during an encoding memory paradigm using blood oxygen level-dependent fMRI. Resting fMRI revealed increased ''default mode network'' (involving retrosplenial, medial temporal, and medial-prefrontal cortical areas) coactivation in 4-carriers relative to noncarriers. The encoding task produced greater hippocampal activation in 4-carriers relative to noncarriers. Neither result could be explained by differences in memory performance, brain morphology, or resting cerebral blood flow. The APOE 4 allele modulates brain function decades before any clinical or neurophysiological expression of neurodegenerative processes.hippocampus ͉ memory ͉ neuroimaging ͉ resting connectivity A polipoprotein E (apoE, protein; APOE, gene) is a very-lowdensity lipoprotein that removes cholesterol from the blood and carries it to the liver for processing (1). In the central nervous system, apoE has a key role in coordinating the mobilization and redistribution of cholesterol, phospholipids, and fatty acids, and it is implicated in mechanisms such as neuronal development, brain plasticity, and repair functions (2). The human APOE gene, which is encoded on chromosome 19, has 3 allelic variants ( 2, 3, and 4). The 4 allele has been associated with a higher risk of cardiovascular disease (3), both early-onset (4) and late-onset (5) Alzheimer's disease (AD), poor outcome from traumatic brain injury (6), and age-related cognitive impairment (7).Neuroimaging studies of the APOE polymorphism in healthy subjects have largely focused on gray matter (GM) alterations in middle or late life, particularly in brain regions associated with the greatest AD pathological findings. Even in asymptomatic subjects, hippocampal and frontotemporal GM reduction has been observed in APOE 4-carriers relative to noncarriers (8). Moreover, a reduction of resting glucose metabolism was reported in young and middle-aged cognitively normal APOE 4-carriers in brain regions known to be affected by AD, including the posterior cingulate, parietal, temporal, and prefrontal cortices (9-11). fMRI task-based studies (mainly investigating memory processes) have shown greater activation in middle-aged and elderly APOE 4-carriers relative to noncarriers (12-16). Although these studies suggest an influence of the APOE 4 allele on brain structure and metabolism, they do not make clear at what age these influences initially manifest. Furthermore, although differences in structure, resting metabolism, and function have each been reported in 4-carriers relative to noncarriers, it remains to be established to what extent these characteristics interact.Thus far, reports of structural and functional eff...

show abstract

“…Resting perfusion maps in units of mL⅐100g⅐min were calculated using tools developed in-house (58) and interrogated using ROIs as defined below.…”

Section: Perfusion Mrimentioning

confidence: 99%

Distinct patterns of brain activity in young carriers of the APOE -ε4 allele

Filippini

MacIntosh

Hough

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

1,521

1,180

View full text Add to dashboard Cite

show abstract

“…Volunteers fasted before the first two visits (6 h for solids; 2 h for clear fluids) and were supervised for 1 h after termination of the infusion. Part of the data, pertaining to technical developments of the imaging and analysis, have previously been reported (Harvey et al, 2008;MacIntosh et al, 2008).…”

Section: Subjectsmentioning

confidence: 99%

“…Registration to anatomical and standard space images was performed using FLIRT (Jenkinson et al, 2002). Additional details of the ASL analysis can be found in the study by MacIntosh et al (2008).…”

Section: Asl Analysismentioning

confidence: 99%

“…Nine subjects underwent a whole-brain ASL sequence to measure changes in CBF induced by remifentanil infusion (MacIntosh et al, 2008). These measurements were incorporated into the higher level fMRI analysis to help account for the confounding effects of global CBF changes on the BOLD signal.…”

Section: Magnetic Resonance Imagingmentioning

confidence: 99%

“…One difficulty with imaging opioid effects in the brain is that the associated respiratory depression leads to a rise in arterial carbon dioxide tension (PaCO 2 ) causing an increase in cerebral blood flow (CBF) (MacIntosh et al, 2008), thereby dampening a task-induced blood oxygen level-dependent (BOLD) response (Cohen et al, 2002). Therefore we measured CBF using an arterial spin-labeling (ASL) technique and incorporated these measurements into our data analysis.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Opioids Depress Cortical Centers Responsible for the Volitional Control of Respiration

Pattinson¹,

Governo²,

MacIntosh³

et al. 2009

Journal of Neuroscience

158

138

View full text Add to dashboard Cite

Respiratory depression limits provision of safe opioid analgesia and is the main cause of death in drug addicts. Although opioids are known to inhibit brainstem respiratory activity, their effects on cortical areas that mediate respiration are less well understood. Here, functional magnetic resonance imaging was used to examine how brainstem and cortical activity related to a short breath hold is modulated by the opioid remifentanil. We hypothesized that remifentanil would differentially depress brain areas that mediate sensoryaffective components of respiration over those that mediate volitional motor control. Quantitative measures of cerebral blood flow were used to control for hypercapnia-induced changes in blood oxygen level-dependent (BOLD) signal. Awareness of respiration, reflected by an urge-to-breathe score, was profoundly reduced with remifentanil. Urge to breathe was associated with activity in the bilateral insula, frontal operculum, and secondary somatosensory cortex. Localized remifentanil-induced decreases in breath hold-related activity were observed in the left anterior insula and operculum. We also observed remifentanil-induced decreases in the BOLD response to breath holding in the left dorsolateral prefrontal cortex, anterior cingulate, the cerebellum, and periaqueductal gray, brain areas that mediate task performance. Activity in areas mediating motor control (putamen, motor cortex) and sensory-motor integration (supramarginal gyrus) were unaffected by remifentanil. Breath hold-related activity was observed in the medulla. These findings highlight the importance of higher cortical centers in providing contextual awareness of respiration that leads to appropriate modulation of respiratory control. Opioids have profound effects on the cortical centers that control breathing, which potentiates their actions in the brainstem.

show abstract

Application of whole‐brain CBV‐weighted fMRI to a cognitive stimulation paradigm: Robust activation detection in a stroop task experiment using 3D GRASE VASO

Poser

Norris

2011

Human Brain Mapping

View full text Add to dashboard Cite

Brain activation studies generally utilize blood oxygenation level dependent (BOLD) contrast, most commonly measured using the gradient-echo echo-planar imaging (EPI) technique. BOLD contrast arises from regional changes in cerebral blood flow (CBF), cerebral blood volume (CBV), and the local metabolic rate of oxygen consumption. An alternative to BOLD is the detection of activation through direct measurement of these parameters. A noninvasive approach to measure activation-related CBV changes is the vascular space occupancy (VASO) method, which exploits blood as an endogenous contrast agent by selectively nulling the magnetization of the water spins in the blood. Using a recently developed multislice variant of VASO that enables single-shot whole-brain coverage by virtue of a three-dimensional GRASE readout, we here present the first application of VASO to an fMRI study with a whole-brain cognitive task. Within acceptable measurement times (∼12 minutes), brain activation during a Stroop color-word matching task could be detected reliably both on the group (N = 12) and single subject level, as evident from a qualitative comparison with separately acquired BOLD data and literature reports.

show abstract

Measuring the Effects of Remifentanil on Cerebral Blood Flow and Arterial Arrival Time Using 3D Grase MRI with Pulsed Arterial Spin Labelling

Cited by 82 publications

References 40 publications

Distinct patterns of brain activity in young carriers of the APOE -ε4 allele

Distinct patterns of brain activity in young carriers of the APOE -ε4 allele

Opioids Depress Cortical Centers Responsible for the Volitional Control of Respiration

Application of whole‐brain CBV‐weighted fMRI to a cognitive stimulation paradigm: Robust activation detection in a stroop task experiment using 3D GRASE VASO

Contact Info

Product

Resources

About