With age, the brain undergoes comprehensive changes in its function and physiology. Cerebral metabolism and blood supply are among the key physiologic processes supporting the daily function of the brain and may play an important role in age-related cognitive decline. Using MRI, it is now possible to make quantitative assessment of these parameters in a noninvasive manner. In the present study, we concurrently measured cerebral metabolic rate of oxygen (CMRO(2)), cerebral blood flow (CBF), and venous blood oxygenation in a well-characterized healthy adult cohort from 20 to 89 years old (N = 232). Our data showed that CMRO(2) increased significantly with age, while CBF decreased with age. This combination of higher demand and diminished supply resulted in a reduction of venous blood oxygenation with age. Regional CBF was also determined, and it was found that the spatial pattern of CBF decline was heterogeneous across the brain with prefrontal cortex, insular cortex, and caudate being the most affected regions. Aside from the resting state parameters, the blood vessels' ability to dilate, measured by cerebrovascular reactivity to 5% CO(2) inhalation, was assessed and was reduced with age, the extent of which was more prominent than that of the resting state CBF.

A better understanding of carbon dioxide (CO 2 ) effect on brain activity may have a profound impact on clinical studies using CO 2 manipulation to assess cerebrovascular reserve and on the use of hypercapnia as a means to calibrate functional magnetic resonance imaging (fMRI) signal. This study investigates how an increase in blood CO 2 , via inhalation of 5% CO 2 , may alter brain activity in humans. Dynamic measurement of brain metabolism revealed that mild hypercapnia resulted in a suppression of cerebral metabolic rate of oxygen (CMRO 2 ) by 13.4% ± 2.3% (N = 14) and, furthermore, the CMRO 2 change was proportional to the subject's end-tidal CO 2 (Et-CO 2 ) change. When using functional connectivity MRI (fcMRI) to assess the changes in resting-state neural activity, it was found that hypercapnia resulted in a reduction in all fcMRI indices assessed including cluster volume, cross-correlation coefficient, and amplitude of the fcMRI signal in the default-mode network (DMN). The extent of the reduction was more pronounced than similar indices obtained in visualevoked fMRI, suggesting a selective suppression effect on resting-state neural activity. Scalp electroencephalogram (EEG) studies comparing hypercapnia with normocapnia conditions showed a relative increase in low frequency power in the EEG spectra, suggesting that the brain is entering a low arousal state on CO 2 inhalation.

Pseudocontinuous arterial spin labeling MRI is a new arterial spin labeling technique that has the potential of combining advantages of continuous arterial spin labeling and pulsed arterial spin labeling. However, unlike continuous arterial spin labeling, the labeling process of pseudocontinuous arterial spin labeling is not strictly an adiabatic inversion and the efficiency of labeling may be subject specific. Here, three experiments were performed to study the labeling efficiency in pseudocontinuous arterial spin labeling MRI. First, the optimal labeling position was determined empirically to be approximately 84 mm below the anterior commissure-posterior commissure line in order to achieve the highest sensitivity. Second, an experimental method was developed to utilize phase-contrast velocity MRI as a normalization factor and to estimate the labeling efficiency in vivo, which was founded to be 0.86 6 0.06 (n 5 10, mean 6 standard deviation). Third, we compared the labeling efficiency of pseudocontinuous arterial spin labeling MRI under normocapnic and hypercapnic (inhalation of 5% CO 2 ) conditions and showed that a higher flow velocity in the feeding arteries resulted in a reduction in the labeling efficiency. In summary, our results suggest that labeling efficiency is a critical parameter in pseudocontinuous arterial spin labeling MRI not only in terms of achieving highest sensitivity but also in quantification of absolute cerebral blood flow in milliliters per minute per 100 g. We propose that the labeling efficiency should be estimated using phase-contrast velocity MRI on a subject-specific basis. Magn Reson Med 63:765-771,

Purpose: To evaluate the feasibility and accuracy of magnetic resonance imaging (MRI)-based treatment planning using pseudo CTs generated through atlas registration. Methods: A pseudo CT, providing electron density information for dose calculation, was generated by deforming atlas CT images previously acquired on other patients. The authors tested 4 schemes of synthesizing a pseudo CT from single or multiple deformed atlas images: use of a single arbitrarily selected atlas, arithmetic mean process using 6 atlases, and pattern recognition with Gaussian process (PRGP) using 6 or 12 atlases. The required deformation for atlas CT images was derived from a nonlinear registration of conjugated atlas MR images to that of the patient of interest. The contrasts of atlas MR images were adjusted by histogram matching to reduce the effect of different sets of acquisition parameters. For comparison, the authors also tested a simple scheme assigning the Hounsfield unit of water to the entire patient volume. All pseudo CT generating schemes were applied to 14 patients with common pediatric brain tumors. The image similarity of real patient-specific CT and pseudo CTs constructed by different schemes was compared. Differences in computation times were also calculated. The real CT in the treatment planning system was replaced with the pseudo CT, and the dose distribution was recalculated to determine the difference. Results: The atlas approach generally performed better than assigning a bulk CT number to the entire patient volume. Comparing atlas-based schemes, those using multiple atlases outperformed the single atlas scheme. For multiple atlas schemes, the pseudo CTs were similar to the real CTs (correlation coefficient, 0.787-0.819). The calculated dose distribution was in close agreement with the original dose. Nearly the entire patient volume (98.3%-98.7%) satisfied the criteria of chi-evaluation (<2% maximum dose and 2 mm range). The dose to 95% of the volume and the percentage of volume receiving at least 95% of the prescription dose in the planning target volume differed from the original values by less than 2% of the prescription dose (root-mean-square, RMS < 1%). The PRGP scheme did not perform better than the arithmetic mean process with the same number of atlases. Increasing the number of atlases from 6 to 12 often resulted in improvements, but statistical significance was not always found. Conclusions: MRI-based treatment planning with pseudo CTs generated through atlas registration is feasible for pediatric brain tumor patients. The doses calculated from pseudo CTs agreed well with those from real CTs, showing dosimetric accuracy within 2% for the PTV when multiple atlases were used. The arithmetic mean process may be a reasonable choice over PRGP for the synthesis scheme considering performance and computational costs.

Epidemiologic evidence and postmortem studies of cerebral amyloid angiopathy suggest that vascular dysfunction may play an important role in the pathogenesis of Alzheimer's Disease (AD). However, alterations in vascular function under in vivo conditions are poorly understood. In this study, we assessed cerebrovascular-reactivity (CVR) in AD patients and age-matched controls using CO2-inhalation while simultaneously acquiring Blood-Oxygenation-Level-Dependent (BOLD) MR images. Compared to controls, AD patients had widespread reduction in CVR in the rostral brain including prefrontal, anterior cingulate, and insular cortex (p<0.01). The deficits could not be explained by cardiovascular risk factors. The spatial distribution of the CVR deficits differed drastically from the regions of cerebral blood flow (CBF) deficits, which were found in temporal and parietal cortices. Individuals with greater CVR deficit tended to have a greater volume of leukoaraiosis as seen on FLAIR MRI (p=0.004). Our data suggest that early AD subjects have evidence of significant forebrain vascular contractility deficits. The localization, while differing from CBF findings, appears to be spatially similar to PIB amyloid imaging findings.

A T2-Relaxation-Under-Spin-Tagging (TRUST) technique was recently developed to estimate cerebral blood oxygenation, providing potentials for non-invasive assessment of the brain's oxygen consumption. A limitation of the current sequence is the need for long TR, as shorter TR causes an over-estimation in blood R2. The present study proposes a post-saturation TRUST by placing a non-selective 90° pulse after the signal acquisition to reset magnetization in the whole brain. This scheme was found to eliminate estimation bias at a slight cost of precision. To improve the precision, TE of the sequence was optimized and it was found that a modest TE shortening of 3.4ms can reduce the estimation error by 49%. We recommend the use of post-saturation TRUST sequence with a TR of 3000ms and a TE of 3.6ms, which allows the determination of global venous oxygenation with scan duration of 1 minute 12 seconds and an estimation precision of ±1% (in units of oxygen saturation percentage).

A major difference between arterial-spin-labeling MRI and gold-standard radiotracer blood flow methods is that the compartment localization of the labeled spins in the arterialspin-labeling image is often ambiguous, which may affect the quantification of cerebral blood flow. In this study, we aim to probe whether the spins are located in the vascular system or tissue by using T2 of the arterial-spin-labeling signal as a marker. We combined two recently developed techniques, pseudo-continuous arterial spin labeling and T2-RelaxationUnder-Spin-Tagging, to determine the T2 of the labeled spins at multiple postlabeling delay times. Our data suggest that the labeled spins first showed the T2 of arterial blood followed by gradually approaching and stabilizing at the tissue T2. The T2 values did not decrease further toward the venous T2. By fitting the experimental data to a two-compartment model, we estimated gray matter cerebral blood flow, arterial transit time, and tissue transit time to be 74.0 6 10.7 mL/ 100g/min (mean 6 SD, N 5 10), 938 6 156 msec, and 1901 6 181 msec, respectively. The arterial blood volume was calculated to be 1.18 6 0.21 mL/100 g. A postlabeling delay time of 2 s is sufficient to allow the spins to completely enter the tissue space for gray matter but not for white matter. Magn Reson Med 65:120-127,

Purpose To investigate differences in the age-related decline in brain tissue concentration between Masters athletes and sedentary older adults. Materials and Methods Twelve Masters athletes (MA) (3 females, age=72.4±5.6yrs, endurance training>15yrs), 12 sedentary elderly (SE) similar in age and educational level (4 females, age=74.6±4.3yrs), and 9 young controls (YC)(4 females, age=27.2±3.6yrs) participated. T1-weighted-high-resolution (1×1×1mm3) images were acquired. Voxel-based analysis was conducted to identify clusters showing tissue concentration differences with t-tests. Cognitive function was assessed using a standard clinical battery focused on executive function and memory. Results Two Masters athletes and 2 sedentary elderly were unable to complete MRI study. Both SE and MA showed lower GM concentrations than YC in the superior, inferior and middle frontal gyrus, superior temporal gyrus, postcentral gyrus and the cingulate gyrus (PFDR-corrected<0.001) and lower WM concentrations in the inferior frontal gyrus and precentral gyrus (PFDR-corrected<0.005). Notably, MA showed higher GM and WM concentrations than SE in the sub-gyral, cuneus, and precuneus regions related to visuospatial function, motor control, and working memory (PFDR-corrected<0.005). After controlling for estimated intelligence, MA outperformed SE on tasks of letter (p<0.01) and category (p<0.05) fluency. Conclusion Life-long exercise may confer benefits to some aspects of executive function and age-related brain tissue loss in the regions related to visuospatial function, motor control, and working memory in older adults.