An 8-Channel Transceiver Coil for Carotid Artery Imaging at 7T Using an Optimized Shield Design.

OBJECTIVE: To design and fabricate a transmit/receive (T/R) radiofrequency (RF) coil array for MRI of the carotid arteries at 7T with optimal shielding to improve transmit performance in parallel transmit (pTx) mode. METHODS: The carotid coil included 8 total RF elements, with left and right subarrays, each consisting of 4 overlapping loops with RF shields. Electromagnetic (EM) simulations were performed to optimize and improve the transmit performance of the array by determining the optimal distance between the RF shield and each subarray. EM simulations were further used to calculate local specific absorption rate (SAR) matrices. Based on the SAR matrices, virtual observation points (VOPs) were applied to ensure safety during parallel transmission. The efficacy of the coil design was evaluated by measuring coil performance metrics when imaging a phantom and by acquiring in-vivo images. RESULTS: The optimal distance between the RF shield and each subarray was determined to be 45 mm. This resulted in a maximum B1+ efficiency of 1.23 µT/ √W in the carotid arteries and a peak, 10-g-average SAR per Watt of 0.86 kg-1 when transmitting in the nominal CP+ mode. Optimizing the RF shield resulted in up to 37% improvement in B1+ efficiency and 14% improvement in SAR efficiency compared to an unshielded design. CONCLUSION AND SIGNIFICANCE: Optimizing the distance between the RF shield and coil array provided significant improvement in the transmit characteristics of the bilateral carotid coil. The bilateral coil topology provides a compelling platform for imaging the carotid arteries with high field MRI.

Neural and behavioral correlates of human pain avoidance in participants with and without episodic migraine.

ABSTRACT: The innate motivation to avoid pain can be disrupted when individuals experience uncontrollable stress, such as pain. This can lead to maladaptive behaviors, including passivity, and negative affect. Despite its importance, motivational aspects of pain avoidance are understudied in humans and their neural mechanisms vastly unknown. Rodent models suggest an important role of the periaqueductal gray, but it is unknown whether it subserves a similar role in humans. Furthermore, it is unclear whether pain avoidance is associated with individual differences in pain coping. Using functional magnetic resonance imaging, networks underlying pain avoidance behavior were examined in 32 participants with and without episodic migraine. Pain avoidance behavior was assessed using an adaptation of the incentive delay task. In each trial of the task, participants tried to avoid a painful stimulus and receive a nonpainful one instead while the difficulty to succeed varied across trials (3 difficulty levels: safe, easy, and difficult). After unsuccessful pain avoidance on the preceding trial, participants showed reduced pain avoidance behavior, especially in the difficult condition. This reduction in behavior was associated with higher helplessness scores only in participants with migraine. Higher helplessness in participants with migraine was further correlated with a stronger decrease in activation of cortical areas associated with motor behavior, attention, and memory after unsuccessful pain avoidance. Of these areas, specifically posterior parietal cortex activation predicted individual's pain avoidance behavior on the next trial. The results link individual pain coping capacity to patterns of neural activation associated with altered pain avoidance in patients with migraine.

Sex moderations in the relationship between aortic stiffness, cognition, and cerebrovascular reactivity in healthy older adults.

It is well established that sex differences exist in the manifestation of vascular diseases. Arterial stiffness (AS) has been associated with changes in cerebrovascular reactivity (CVR) and cognitive decline in aging. Specifically, older adults with increased AS show a decline on executive function (EF) tasks. Interestingly, the relationship between AS and CVR is more complex, where some studies show decreased CVR with increased AS, and others demonstrate preserved CVR despite higher AS. Here, we investigated the possible role of sex on these hemodynamic relationships. Acquisitions were completed in 48 older adults. Pseudo-continuous arterial spin labeling (pCASL) data were collected during a hypercapnia challenge. Aortic pulse wave velocity (PWV) data was acquired using cine phase contrast velocity series. Cognitive function was assessed with a comprehensive neuropsychological battery, and a composite score for EF was calculated using four cognitive tests from the neuropsychological battery. A moderation model test revealed that sex moderated the relationship between PWV and CVR and PWV and EF, but not between CVR and EF. Together, our results indicate that the relationships between central stiffness, cerebral hemodynamics and cognition are in part mediated by sex.

Open science datasets from PREVENT-AD, a longitudinal cohort of pre-symptomatic Alzheimer's disease.

To move Alzheimer Disease (AD) research forward it is essential to collect data from large cohorts, but also make such data available to the global research community. We describe the creation of an open science dataset from the PREVENT-AD (PResymptomatic EValuation of Experimental or Novel Treatments for AD) cohort, composed of cognitively unimpaired older individuals with a parental or multiple-sibling history of AD. From 2011 to 2017, 386 participants were enrolled (mean age 63 years old ± 5) for sustained investigation among whom 349 have retrospectively agreed to share their data openly. Repositories are findable through the unified interface of the Canadian Open Neuroscience Platform and contain up to five years of longitudinal imaging data, cerebral fluid biochemistry, neurosensory capacities, cognitive, genetic, and medical information. Imaging data can be accessed openly at https://openpreventad.loris.ca while most of the other information, sensitive by nature, is accessible by qualified researchers at https://registeredpreventad.loris.ca. In addition to being a living resource for continued data acquisition, PREVENT-AD offers opportunities to facilitate understanding of AD pathogenesis.

Higher cardiovascular fitness level is associated with lower cerebrovascular reactivity and perfusion in healthy older adults.

Aging is accompanied by vascular and structural changes in the brain, which include decreased grey matter volume (GMV), cerebral blood flow (CBF), and cerebrovascular reactivity (CVR). Enhanced fitness in aging has been related to preservation of GMV and CBF, and in some cases CVR, although there are contradictory relationships reported between CVR and fitness. To gain a better understanding of the complex interplay between fitness and GMV, CBF and CVR, the present study assessed these factors concurrently. Data from 50 participants, aged 55 to 72, were used to derive GMV, CBF, CVR and VO2peak. Results revealed that lower CVR was associated with higher VO2peak throughout large areas of the cerebral cortex. Within these regions lower fitness was associated with higher CBF and a faster hemodynamic response to hypercapnia. Overall, our results indicate that the relationships between age, fitness, cerebral health and cerebral hemodynamics are complex, likely involving changes in chemosensitivity and autoregulation in addition to changes in arterial stiffness. Future studies should collect other physiological outcomes in parallel with quantitative imaging, such as measures of chemosensitivity and autoregulation, to further understand the intricate effects of fitness on the aging brain, and how this may bias quantitative measures of cerebral health.

Age differences in brain signal variability are robust to multiple vascular controls.

A host of studies support that younger, better performing adults express greater moment-to-moment blood oxygen level-dependent (BOLD) signal variability (SDBOLD) in various cortical regions, supporting an emerging view that the aging brain may undergo a generalized reduction in dynamic range. However, the exact physiological nature of age differences in SDBOLD remains understudied. In a sample of 29 younger and 45 older adults, we examined the contribution of vascular factors to age group differences in fixation-based SDBOLD using (1) a dual-echo BOLD/pseudo-continuous arterial spin labeling (pCASL) sequence, and (2) hypercapnia via a computer-controlled gas delivery system. We tested the hypothesis that, although SDBOLD may relate to individual differences in absolute cerebral blood flow (CBF), BOLD cerebrovascular reactivity (CVR), or maximum BOLD signal change (M), robust age differences in SDBOLD would remain after multiple statistical controls for these vascular factors. As expected, our results demonstrated that brain regions in which younger adults expressed higher SDBOLD persisted after comprehensive control of vascular effects. Our findings thus further establish BOLD signal variability as an important marker of the aging brain.

Application of calibrated fMRI in Alzheimer's disease.

Calibrated fMRI based on arterial spin-labeling (ASL) and blood oxygen-dependent contrast (BOLD), combined with periods of hypercapnia and hyperoxia, can provide information on cerebrovascular reactivity (CVR), resting blood flow (CBF), oxygen extraction fraction (OEF), and resting oxidative metabolism (CMRO2). Vascular and metabolic integrity are believed to be affected in Alzheimer's disease (AD), thus, the use of calibrated fMRI in AD may help understand the disease and monitor therapeutic responses in future clinical trials. In the present work, we applied a calibrated fMRI approach referred to as Quantitative O2 (QUO2) in a cohort of probable AD dementia and age-matched control participants. The resulting CBF, OEF and CMRO2 values fell within the range from previous studies using positron emission tomography (PET) with 15O labeling. Moreover, the typical parietotemporal pattern of hypoperfusion and hypometabolism in AD was observed, especially in the precuneus, a particularly vulnerable region. We detected no deficit in frontal CBF, nor in whole grey matter CVR, which supports the hypothesis that the effects observed were associated specifically with AD rather than generalized vascular disease. Some key pitfalls affecting both ASL and BOLD methods were encountered, such as prolonged arterial transit times (particularly in the occipital lobe), the presence of susceptibility artifacts obscuring medial temporal regions, and the challenges associated with the hypercapnic manipulation in AD patients and elderly participants. The present results are encouraging and demonstrate the promise of calibrated fMRI measurements as potential biomarkers in AD. Although CMRO2 can be imaged with 15O PET, the QUO2 method uses more widely available imaging infrastructure, avoids exposure to ionizing radiation, and integrates with other MRI-based measures of brain structure and function.

The impact of inspired oxygen levels on calibrated fMRI measurements of M, OEF and resting CMRO2 using combined hypercapnia and hyperoxia.

Recent calibrated fMRI techniques using combined hypercapnia and hyperoxia allow the mapping of resting cerebral metabolic rate of oxygen (CMRO2) in absolute units, oxygen extraction fraction (OEF) and calibration parameter M (maximum BOLD). The adoption of such technique necessitates knowledge about the precision and accuracy of the model-derived parameters. One of the factors that may impact the precision and accuracy is the level of oxygen provided during periods of hyperoxia (HO). A high level of oxygen may bring the BOLD responses closer to the maximum M value, and hence reduce the error associated with the M interpolation. However, an increased concentration of paramagnetic oxygen in the inhaled air may result in a larger susceptibility area around the frontal sinuses and nasal cavity. Additionally, a higher O2 level may generate a larger arterial blood T1 shortening, which require a bigger cerebral blood flow (CBF) T1 correction. To evaluate the impact of inspired oxygen levels on M, OEF and CMRO2 estimates, a cohort of six healthy adults underwent two different protocols: one where 60% of O2 was administered during HO (low HO or LHO) and one where 100% O2 was administered (high HO or HHO). The QUantitative O2 (QUO2) MRI approach was employed, where CBF and R2* are simultaneously acquired during periods of hypercapnia (HC) and hyperoxia, using a clinical 3 T scanner. Scan sessions were repeated to assess repeatability of results at the different O2 levels. Our T1 values during periods of hyperoxia were estimated based on an empirical ex-vivo relationship between T1 and the arterial partial pressure of O2. As expected, our T1 estimates revealed a larger T1 shortening in arterial blood when administering 100% O2 relative to 60% O2 (T1LHO = 1.56±0.01 sec vs. T1HHO = 1.47±0.01 sec, P < 4*10-13). In regard to the susceptibility artifacts, the patterns and number of affected voxels were comparable irrespective of the O2 concentration. Finally, the model-derived estimates were consistent regardless of the HO levels, indicating that the different effects are adequately accounted for within the model.

GABA and glutamate levels correlate with MTR and clinical disability: Insights from multiple sclerosis.

Converging areas of research have implicated glutamate and γ-aminobutyric acid (GABA) as key players in neuronal signalling and other central functions. Further research is needed, however, to identify microstructural and behavioral links to regional variability in levels of these neurometabolites, particularly in the presence of demyelinating disease. Thus, we sought to investigate the extent to which regional glutamate and GABA levels are related to a neuroimaging marker of microstructural damage and to motor and cognitive performance. Twenty-one healthy volunteers and 47 people with multiple sclerosis (all right-handed) participated in this study. Motor and cognitive abilities were assessed with standard tests used in the study of multiple sclerosis. Proton magnetic resonance spectroscopy data were acquired from sensorimotor and parietal regions of the brains' left cerebral hemisphere using a MEGA-PRESS sequence. Our analysis protocol for the spectroscopy data was designed to account for confounding factors that could contaminate the measurement of neurometabolite levels due to disease, such as the macromolecule signal, partial volume effects, and relaxation effects. Glutamate levels in both regions of interest were lower in people with multiple sclerosis. In the sensorimotor (though not the parietal) region, GABA concentration was higher in the multiple sclerosis group compared to controls. Lower magnetization transfer ratio within grey and white matter regions from which spectroscopy data were acquired was linked to neurometabolite levels. When adjusting for age, normalized brain volume, MTR, total N-acetylaspartate level, and glutamate level, significant relationships were found between lower sensorimotor GABA level and worse performance on several tests, including one of upper limb motor function. This work highlights important methodological considerations relevant to analysis of spectroscopy data, particularly in the afflicted human brain. These findings support that regional neurotransmitter levels are linked to local microstructural integrity and specific behavioral abilities that can be affected in diseases such as multiple sclerosis.

Regional Reproducibility of BOLD Calibration Parameter M, OEF and Resting-State CMRO2 Measurements with QUO2 MRI.

The current generation of calibrated MRI methods goes beyond simple localization of task-related responses to allow the mapping of resting-state cerebral metabolic rate of oxygen (CMRO2) in micromolar units and estimation of oxygen extraction fraction (OEF). Prior to the adoption of such techniques in neuroscience research applications, knowledge about the precision and accuracy of absolute estimates of CMRO2 and OEF is crucial and remains unexplored to this day. In this study, we addressed the question of methodological precision by assessing the regional inter-subject variance and intra-subject reproducibility of the BOLD calibration parameter M, OEF, O2 delivery and absolute CMRO2 estimates derived from a state-of-the-art calibrated BOLD technique, the QUantitative O2 (QUO2) approach. We acquired simultaneous measurements of CBF and R2* at rest and during periods of hypercapnia (HC) and hyperoxia (HO) on two separate scan sessions within 24 hours using a clinical 3 T MRI scanner. Maps of M, OEF, oxygen delivery and CMRO2, were estimated from the measured end-tidal O2, CBF0, CBFHC/HO and R2*HC/HO. Variability was assessed by computing the between-subject coefficients of variation (bwCV) and within-subject CV (wsCV) in seven ROIs. All tests GM-averaged values of CBF0, M, OEF, O2 delivery and CMRO2 were: 49.5 ± 6.4 mL/100 g/min, 4.69 ± 0.91%, 0.37 ± 0.06, 377 ± 51 µmol/100 g/min and 143 ± 34 µmol/100 g/min respectively. The variability of parameter estimates was found to be the lowest when averaged throughout all GM, with general trends toward higher CVs when averaged over smaller regions. Among the MRI measurements, the most reproducible across scans was R2*0 (wsCVGM = 0.33%) along with CBF0 (wsCVGM = 3.88%) and R2*HC (wsCVGM = 6.7%). CBFHC and R2*HO were found to have a higher intra-subject variability (wsCVGM = 22.4% and wsCVGM = 16% respectively), which is likely due to propagation of random measurement errors, especially for CBFHC due to the low contrast-to-noise ratio intrinsic to ASL. Reproducibility of the QUO2 derived estimates were computed, yielding a GM intra-subject reproducibility of 3.87% for O2 delivery, 16.8% for the M value, 13.6% for OEF and 15.2% for CMRO2. Although these results focus on the precision of the QUO2 method, rather than the accuracy, the information will be useful for calculation of statistical power in future validation studies and ultimately for research applications of the method. The higher test-retest variability for the more extensively modeled parameters (M, OEF, and CMRO2) highlights the need for further improvement of acquisition methods to reduce noise levels.

The effect of dissolved oxygen on the susceptibility of blood.

PURPOSE: It has been predicted that, during hyperoxia, excess O2 dissolved in arterial blood will significantly alter the blood's magnetic susceptibility. This would confound the interpretation of the hyperoxia-induced blood oxygenation level-dependent signal as arising solely from changes in deoxyhemoglobin. This study, therefore, aimed to determine how dissolved O2 affects the susceptibility of blood. THEORY AND METHODS: We present a comprehensive model for the effect of dissolved O2 on the susceptibility of blood and compare it with another recently published model, referred to here as the ideal gas model (IGM). For validation, distilled water and samples of bovine plasma were oxygenated over a range of hyperoxic O2 concentrations and their susceptibilities were determined using multiecho gradient echo phase imaging. RESULTS: In distilled water and plasma, the measured changes in susceptibility were very linear, with identical slopes of 0.062 ppb/mm Hg of O2. This change was dramatically less than previously predicted using the IGM and was close to that predicted by our model. The primary source of error in the IGM is the overestimation of the volume fraction occupied by dissolved O2. CONCLUSION: Under most physiological conditions, the susceptibility of dissolved O2 can be disregarded in MRI studies employing hyperoxia.

Test-retest reliability of cerebral blood flow and blood oxygenation level-dependent responses to hypercapnia and hyperoxia using dual-echo pseudo-continuous arterial spin labeling and step changes in the fractional composition of inspired gases.

PURPOSE: To assess the reproducibility of blood oxygenation level-dependent / cerebral blood flow (BOLD/CBF) responses to hypercapnia/hyperoxia using dual-echo pseudo-continuous arterial spin labeling (pCASL) and step changes in inspired doses. MATERIALS AND METHODS: Eight subjects were scanned twice, within 24 hours, using the same respiratory manipulation and imaging protocol. Imaging comprised a 5-minute anatomical acquisition, allowing segmentation of the gray matter (GM) tissue for further analysis, and an 18-minute pCASL functional scan. Hypercapnia/hyperoxia were induced by increasing the fraction of inspired CO2 to 5% and inspired O2 to 60%, alternately. Reproducibility of BOLD and CBF pCASL measures was assessed by computing the inter-session coefficient of variation (CV) of the respective signals in GM. RESULTS: BOLD and CBF measures in GM were robust and consistent, yielding CV values below 10% for BOLD hypercapnic/hyperoxic responses (which averaged 1.9 ± 0.1% and 1.14 ± 0.02%) and below 20% for the CBF hypercapnic response (which averaged 35 ± 2 mL/min/100g). The CV for resting CBF was 3.5%. CONCLUSION: It is possible to attain reproducible measures of the simultaneous BOLD and CBF responses to blood gases, within a reasonable scan time and with whole brain coverage, using a simple respiratory manipulation and dual-echo pCASL.

Hearts and minds: linking vascular rigidity and aerobic fitness with cognitive aging.

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 ± 211.10 ms 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 ± 0.82 m/s, respectively) and lower VO2 max (29.04 ± 6.92 vs. 42.32 ± 7.31 mL 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.

A simple breathing circuit allowing precise control of inspiratory gases for experimental respiratory manipulations.

BACKGROUND: Respiratory manipulations modulating blood flow and oxygenation levels have become an important component of modern functional MRI applications. Manipulations often consist of temporarily switching inspired fractions of CO2 and O2; and have typically been performed using simple oxygen masks intended for applications in respiratory therapy. However, precise control of inspired gas composition is difficult using this type of mask due to entrainment of room air and resultant dilution of inspired gases. We aimed at developing a gas delivery apparatus allowing improved control over the fractional concentration of inspired gases, to be used in brain fMRI studies. FINDINGS: The breathing circuit we have conceived allowed well controlled step changes in FiO2 and FiCO2, at moderate flow rates achievable on standard clinical flow regulators. In a two run test inside the scanner we demonstrate that tightly controlled simple gas switching manipulations can afford good intra-subject reproducibility of induced hyperoxia/hypercapnia responses. Although our approach requires a non-vented mask fitting closely to the subject's face, the circuit ensures a continuous supply of breathable air even if the supply of medical gases is interrupted, and is easily removable in case of an emergency. The apparatus we propose is also compact and MRI compatible, allowing subject placement in confined spaces such as an MRI scanner for brain examinations. CONCLUSIONS: We have reported a new approach for the controlled administration of medical gases, and describe an implementation of the breathing circuit that is MRI compatible and uses commercially available parts. The resultant apparatus allows simple, safe and precise manipulations of FiO2 and FiCO2.

Cerebrovascular perfusion among older adults is moderated by strength training and gender.

Cerebral perfusion is important in older adults as it is linked to cognitive declines. Physical activity can improve blood flow in the body but little is known about the relationship between physical activity and cerebral perfusion in older adults. In particular, no study has investigated the relation between strength training and cerebral perfusion. We examined whether different types of physical activity (assessed with the Rapid Assessment of Physical Activity questionnaire) were associated with MRI cerebrovascular perfusion in 59 older adults. There was a significant interaction between gender and strength training, such that women who engaged in strength training (weight lifting or calisthenics) at least once per week exhibited significantly greater cerebrovascular perfusion than women who did not. This interaction remained significant after controlling for other physical activity, demographics, and health variables. These findings suggest that regular strength training can be beneficial for cerebrovascular health in women.

Comparison of cerebral vascular reactivity measures obtained using breath-holding and CO2 inhalation.

Stimulation of cerebral vasculature using hypercapnia has been widely used to study cerebral vascular reactivity (CVR), which can be expressed as the quantitative change in cerebral blood flow (CBF) per mm Hg change in end-tidal partial pressure of CO2 (PETCO2). We investigate whether different respiratory manipulations, with arterial spin labeling used to measure CBF, lead to consistent measures of CVR. The approaches included: (1) an automated system delivering variable concentrations of inspired CO2 for prospective targeting of PETCO2, (2) administration of a fixed concentration of CO2 leading to subject-dependent changes in PETCO2, (3) a breath-hold (BH) paradigm with physiologic modeling of CO2 accumulation, and (4) a maneuver combining breath-hold and hyperventilation. When CVR was expressed as the percent change in CBF per mm Hg change in PETCO2, methods 1 to 3 gave consistent results. The CVR values using method 4 were significantly lower. When CVR was expressed in terms of the absolute change in CBF (mL/100 g per minute per mm Hg), greater discrepancies became apparent: methods 2 and 3 gave lower absolute CVR values compared with method 1, and the value obtained with method 4 was dramatically lower. Our findings indicate that care must be taken to ensure that CVR is measured over the linear range of the CBF-CO2 dose-response curve, avoiding hypocapnic conditions.

Sleep spindles predict neural and behavioral changes in motor sequence consolidation.

The purpose of this study was to investigate the predictive function of sleep spindles in motor sequence consolidation. BOLD responses were acquired in 10 young healthy subjects who were trained on an explicitly known 5-item sequence using their left nondominant hand, scanned at 9:00 pm while performing that same task and then were retested and scanned 12 h later after a night of sleep during which polysomnographic measures were recorded. An automatic algorithm was used to detect sleep spindles and to quantify their characteristics (i.e., density, amplitude, and duration). Analyses revealed significant positive correlations between gains in performance and the amplitude of spindles. Moreover, significant increases in BOLD signal were observed in several motor-related areas, most of which were localized in the right hemisphere, particularly in the right cortico-striatal system. Such increases in BOLD signal also correlated positively with the amplitude of spindles at several derivations. Taken together, our results show that sleep spindles predict neural and behavioral changes in overnight motor sequence consolidation.

Age dependence of hemodynamic response characteristics in human functional magnetic resonance imaging.

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.

A generalized procedure for calibrated MRI incorporating hyperoxia and hypercapnia.

Calibrated MRI techniques use the changes in cerebral blood flow (CBF) and blood oxygenation level-dependent (BOLD) signal evoked by a respiratory manipulation to extrapolate the total BOLD signal attributable to deoxyhemoglobin at rest (M). This parameter can then be used to estimate changes in the cerebral metabolic rate of oxygen consumption (CMRO(2)) based on task-induced BOLD and CBF signals. Different approaches have been described previously, including addition of inspired CO(2) (hypercapnia) or supplemental O(2) (hyperoxia). We present here a generalized BOLD signal model that reduces under appropriate conditions to previous models derived for hypercapnia or hyperoxia alone, and is suitable for use during hybrid breathing manipulations including simultaneous hypercapnia and hyperoxia. This new approach yields robust and accurate M maps, in turn allowing more reliable estimation of CMRO(2) changes evoked during a visual task. The generalized model is valid for arbitrary flow changes during hyperoxia, thus benefiting from the larger total oxygenation changes produced by increased blood O(2) content from hyperoxia combined with increases in flow from hypercapnia. This in turn reduces the degree of extrapolation required to estimate M. The new procedure yielded M estimates that were generally higher (7.6 ± 2.6) than those obtained through hypercapnia (5.6 ± 1.8) or hyperoxia alone (4.5 ± 1.5) in visual areas. These M values and their spatial distribution represent a more accurate and robust depiction of the underlying distribution of tissue deoxyhemoglobin at rest, resulting in more accurate estimates of evoked CMRO(2) changes.

Comparison of pulsed and pseudocontinuous arterial spin-labeling for measuring CO2 -induced cerebrovascular reactivity.

PURPOSE: To compare the performance of pulsed and pseudocontinuous arterial spin-labeling (PASL and pCASL) methods in measuring CO(2) -induced cerebrovascular reactivity (CVR). MATERIALS AND METHODS: Subjects were scanned using both ASL sequences during a controlled hypercapnia procedure and visual stimulation. CVR was computed as the percent CO(2) -induced increase in cerebral blood flow (Δ%CBF) per mmHg increase in end-tidal PCO(2) . Visually evoked responses were expressed as Δ%CBF. Resting CBF and temporal signal-to-noise ratio were also computed. Regionally averaged values for the different quantities were compared in gray matter (GM) and visual cortex (VC) using t-tests. RESULTS: Both PASL and pCASL yielded comparable respective values for resting CBF (56 ± 3 and 56 ± 4 mL/min/100g) and visually evoked responses (75 ± 5% and 81 ± 4%). Values of CVR determined using pCASL (GM 4.4 ± 0.2, VC 8 ± 1 Δ%CBF/mmHg), however, were significantly higher than those measured using PASL (GM 3.0 ± 0.6, VC 5 ± 1 Δ%CBF/mmHg) in both GM and VC. The percentage of GM voxels in which statistically significant hypercapnia responses were detected was also higher for pCASL (27 ± 5% vs. 16 ± 3% for PASL). CONCLUSION: pCASL may be less prone to underestimation of CO(2) -induced flow changes due to improved label timing control.