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Montréal, Canada
Montréal, Canada
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Gauthier C.J.,University of Montréal | Desjardins-Crepeau L.,CRIUGM | Madjar C.,CRIUGM | Bherer L.,CRIUGM | Hoge R.D.,University of Montréal
NeuroImage | Year: 2012

We have recently described an extension of calibrated MRI, which we term QUO2 (for QUantitative O2 imaging), providing absolute quantification of resting oxidative metabolism (CMRO2) and oxygen extraction fraction (OEF0). By combining BOLD, arterial spin labeling (ASL) and end-tidal O2 measurements in response to hypercapnia, hyperoxia and combined hyperoxia/hypercapnia manipulations, and the same MRI measurements during a task, a comprehensive set of vascular and metabolic measurements can be obtained using a generalized calibration model (GCM). These include the baseline absolute CBF in units of ml/100g/min, cerebrovascular reactivity (CVR) in units of %δ CBF/mm Hg, M in units of percent, OEF0 and CMRO2 at rest in units of μmol/100g/min, percent evoked CMRO2 during the task and n, the value for flow-metabolic coupling associated with the task. The M parameter is a calibration constant corresponding to the maximal BOLD signal that would occur upon removal of all deoxyhemoglobin. We have previously shown that the GCM provides estimates of the above resting parameters in grey matter that are in excellent agreement with literature. Here we demonstrate the method using functionally-defined regions-of-interest in the context of an activation study. We applied the method under high and low signal-to-noise conditions, corresponding respectively to a robust visual stimulus and a modified Stroop task. The estimates fall within the physiological range of literature values, showing the general validity of the GCM approach to yield non-invasively an extensive array of relevant vascular and metabolic parameters. © 2012 Elsevier Inc.


Gauthier C.J.,University of Montréal | Madjar C.,Criugm | Tancredi F.B.,University of Montréal | Stefanovic B.,University of Toronto | Hoge R.D.,University of Montréal
NeuroImage | Year: 2011

Breathing a mixture of 10% CO2 with 90% O2 (referred to here as carbogen-10) increases blood flow due to the vasodilatory effect of CO2, and raises blood O2 saturation due to the enriched oxygen level. These effects both tend to reduce the level of deoxygenated hemoglobin in brain tissues, thereby reducing the potential for further increases in BOLD contrast. In the present study, blocks of intense visual stimulation (60s) were presented amid longer blocks (180s) during which subjects breathed various fractional concentrations (0-100%) of carbogen-10 diluted with medical air. When breathing undiluted carbogen-10, the BOLD response to visual stimulation was reduced below the level of noise against the background of the carbogen-10 response. At these concentrations, the total (visual+carbogen) BOLD response amplitude (7.5±1.0%, n=6) converged toward that seen with carbogen alone (7.5±1.0%, n=6). In spite of the almost complete elimination of the visual BOLD response, pseudo-continuous arterial spin-labeling on a separate cohort indicated a largely preserved perfusion response (89±34%, n=5) to the visual stimulus during inhalation of carbogen-10.The previously discussed observations suggest that venous saturation can be driven to very high levels during carbogen inhalation, a finding which has significant implications for calibrated MRI techniques. The latter methods involve estimation of the relative change in venous O2 saturation by expressing activation-induced BOLD signal increases as a fraction of the maximal BOLD signal M that would be observed as venous saturation approaches 100%. While the value of M has generally been extrapolated from much smaller BOLD responses induced using hypercapnia or hyperoxia, our results suggest that these effects could be combined through carbogen inhalation to obtain estimates of M based on larger BOLD increases. Using a hybrid BOLD calibration model taking into account changes in both blood flow and arterial oxygenation, we estimated that inhalation of carbogen-10 led to an average venous saturation of 91%, allowing us to compute an estimated M value of 9.5%. © 2010 Elsevier Inc.


Gauthier C.J.,University of Montréal | Gauthier C.J.,Max Planck Institute for Human Cognitive and Brain Sciences | Lefort M.,University Pierre and Marie Curie | Mekary S.,CRIUGM | And 16 more authors.
Neurobiology of Aging | Year: 2015

Human aging is accompanied by both vascular and cognitive changes. Although arteries throughout the body are known to become stiffer with age, this vessel hardening is believed to start at the level of the aorta and progress to other organs, including the brain. Progression of this vascular impairment may contribute to cognitive changes that arise with a similar time course during aging. Conversely, it has been proposed that regular exercise plays a protective role, attenuating the impact of age on vascular and metabolic physiology. Here, the impact of vascular degradation in the absence of disease was investigated within 2 groups of healthy younger and older adults. Age-related changes in executive function, elasticity of the aortic arch, cardiorespiratory fitness, and cerebrovascular reactivity were quantified, as well as the association between these parameters within the older group. In the cohort studied, older adults exhibited a decline in executive functions, measured as a slower performance in a modified Stroop task (1247.90 ± 204.50 vs. 898.20 ± 211.10ms on the inhibition and/or switching component, respectively) than younger adults. Older participants also showed higher aortic pulse wave velocity (8.98 ± 3.56 vs. 3.95 ± 0.82m/s, respectively) and lower VO2 max (29.04 ± 6.92 vs. 42.32 ± 7.31mL O2/kg/min, respectively) than younger adults. Within the older group, faster performance of the modified Stroop task was associated with preserved aortic elasticity (lower aortic pulse wave velocity; p = 0.046) and higher cardiorespiratory fitness (VO2 max; p = 0.036). Furthermore, VO2 max was found to be negatively associated with blood oxygenation level dependent cerebrovascular reactivity to CO2 in frontal regions involved in the task (p = 0.038) but positively associated with cerebrovascular reactivity in periventricular watershed regions and within the postcentral gyrus. Overall, the results of this study support the hypothesis that cognitive status in aging is linked to vascular health, and that preservation of vessel elasticity may be one of the key mechanisms by which physical exercise helps to alleviate cognitive aging. © 2015 Elsevier Inc.


Gauthier C.J.,University of Montréal | Madjar C.,CRIUGM | Desjardins-Crepeau L.,CRIUGM | Bellec P.,CRIUGM | And 3 more authors.
Neurobiology of Aging | Year: 2013

Functional magnetic resonance imaging (fMRI) studies of cognitive aging have generally compared the amplitude and extent of blood oxygen level-dependent (BOLD) signal increases evoked by a task in older and younger groups. BOLD is thus used as a direct index of neuronal activation and it is assumed that the relationship between neuronal activity and the hemodynamic response is unchanged across the lifespan. However, even in healthy aging, differences in vascular and metabolic function have been observed that could affect the coupling between neuronal activity and the BOLD signal. Here we use a calibrated fMRI method to explore vascular and metabolic changes that might bias such BOLD comparisons. Though BOLD signal changes evoked by a cognitive task were found to be similar between a group of younger and older adults (e.g., 0.50 ± 0.04% vs. 0.50 ± 0.05% in right frontal areas), comparison of BOLD and arterial spin labelling (ASL) responses elicited in the same set of structures by a controlled global hypercapnic manipulation revealed significant differences between the 2 groups. Older adults were found to have lower responses in BOLD and flow responses to hypercapnia (e.g., 1.48 ± 0.07% vs. 1.01 ± 0.06% over gray matter for BOLD and 24.92 ± 1.37% vs. 20.67 ± 2.58% for blood flow), and a generally lower maximal BOLD response M (5.76 ± 0.2% vs. 5.00 ± 0.3%). This suggests that a given BOLD response in the elderly might represent a larger change in neuronal activity than the same BOLD response in a younger cohort. The results of this study highlight the importance of ancillary measures such as ASL for the correct interpretation of BOLD responses when fMRI responses are compared across populations who might exhibit differences in vascular physiology. © 2013 Elsevier Inc.

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