Jinsoo Uh

The influence of carbon dioxide on brain activity and metabolism in conscious humans

A better understanding of carbon dioxide (CO2) effect on brain activity may have a profound impact on clinical studies using CO2 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 CO2, via inhalation of 5% CO2, 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 subjects end-tidal CO2 (Et-CO2) 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 visual-evoked 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 CO2 inhalation.

Estimation of labeling efficiency in pseudocontinuous arterial spin labeling

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 ± 0.06 (n = 10, mean ± standard deviation). Third, we compared the labeling efficiency of pseudocontinuous arterial spin labeling MRI under normocapnic and hypercapnic (inhalation of 5% CO2) 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, 2010.

Forebrain-dominant deficit in cerebrovascular reactivity in Alzheimer's disease.

Epidemiologic evidence and postmortem studies of cerebral amyloid angiopathy suggest that vascular dysfunction may play an important role in the pathogenesis of Alzheimers 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 CO(2)-inhalation while simultaneously acquiring Blood-Oxygenation-Level-Dependent (BOLD) MR images. Compared with 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.

Determination of spin compartment in Arterial Spin Labeling MRI

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 arterial‐spin‐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‐Relaxation‐Under‐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 ± 10.7 mL/100g/min (mean ± SD, N = 10), 938 ± 156 msec, and 1901 ± 181 msec, respectively. The arterial blood volume was calculated to be 1.18 ± 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, 2010.

Alterations in resting functional connectivity due to recent motor task

The impact of recent experiences of task performance on resting functional connectivity MRI (fcMRI) has important implications for the design of many neuroimaging studies, because, if an effect is present, the fcMRI scan then must be performed before any evoked fMRI or after a time gap to allow it to dissipate. The present study aims to determine the effect of simple button presses, which are used in many cognitive fMRI tasks as a response recording method, on later acquired fcMRI data. Human volunteers were subject to a 23-minute button press motor task. Their resting-state brain activity before and after the task was assessed with fcMRI. It was found that, compared to the pre-task resting period, the post-task resting fcMRI revealed a significantly higher (p=0.002, N=24) cross correlation coefficient (CC) between left and right motor cortices. These changes were not present in sham control studies that matched the paradigm timing but had no actual task. The amplitude of fcMRI signal fluctuation (AF) also demonstrated an increase in the post-task period compared to pre-task. These changes were observed using both the right-hand-only task and the two-hand task. Study of the recovery time course of these effects revealed that the CC changes lasted for about 5 min while the AF change lasted for at least 15 min. Finally, voxelwise analysis revealed that the pre/post-task differences were also observed in several other brain regions, including the auditory cortex, visual areas, and the thalamus. Our data suggest that the recent performance of the simple button press task can result in elevated fcMRI CC and AF in relevant brain networks and that fcMRI scan should be performed either before evoked fMRI or after a sufficient time gap following fMRI.

On improving the speed and reliability of T2-Relaxation-Under-Spin-Tagging (TRUST) MRI

A T2‐relaxation‐under‐spin‐tagging technique was recently developed to estimate cerebral blood oxygenation, providing potentials for noninvasive assessment of the brains oxygen consumption. A limitation of the current sequence is the need for long repetition time, as shorter repetition time causes an over‐estimation in blood R2. This study proposes a postsaturation T2‐relaxation‐under‐spin‐tagging by placing a nonselective 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, echo time of the sequence was optimized and it was found that a modest echo time shortening of 3.4 ms can reduce the estimation error by 49%. We recommend the use of postsaturation T2‐relaxation‐under‐spin‐tagging sequence with a repetition time of 3000 ms and a echo time of 3.6 ms, which allows the determination of global venous oxygenation with scan duration of 1 min 12 s and an estimation precision of ±1% (in units of oxygen saturation percentage). Magn Reson Med, 2012.

Masters Athletes Exhibit Larger Regional Brain Volume and Better Cognitive Performance than Sedentary Older Adults

To investigate differences in the age‐related decline in brain tissue concentration between Masters athletes and sedentary older adults.

In vivo vascular hallmarks of diffuse leukoaraiosis

To characterize multiple patterns of vascular changes in leukoaraiosis using in vivo magnetic resonance imaging (MRI) techniques.

White matter cerebral blood flow is inversely correlated with structural and functional connectivity in the human brain

White matter provides anatomic connections among brain regions and has received increasing attention in understanding brain intrinsic networks and neurological disorders. Despite significant progresses made in characterizing the white matters structural properties using post-mortem techniques and in vivo diffusion-tensor-imaging (DTI) methods, its physiology remains poorly understood. In the present study, cerebral blood flow (CBF) of the white matter was investigated on a fiber tract-specific basis using MRI (n=10, 25-33 years old). It was found that CBF in the white matter varied considerably, up to a factor of two between fiber groups. Furthermore, a paradoxically inverse correlation was observed between white matter CBF and structural and functional connectivities (P<0.001). Fiber tracts that had a higher CBF tended to have a lower fractional anisotropy in water diffusion, and the gray matter terminals connected to the tract also tended to have a lower temporal synchrony in resting-state BOLD signal fluctuation. These findings suggest a clear association between white matter perfusion and gray matter activity, but the nature of this relationship requires further investigations given that they are negatively, rather than positively, correlated.

Validation of VASO cerebral blood volume measurement with positron emission tomography

Cerebral blood volume (CBV) has been shown to be an important biomarker in a number of neurological disorders and in the quantitative interpretation of functional MRI. One approach to determine CBV in humans is vascular‐space‐occupancy MRI, and this technique has been applied to the studies of brain glioma, Schizophrenia, and Alzheimers disease. However, validation of this technique with a gold standard method has not been reported. In this study, we compared vascular‐space‐occupancy MRI with a radiotracer‐based positron emission tomography technique in a group of healthy subjects. It was found that regional CBV measured with vascular‐space‐occupancy MRI was highly correlated with that of the positron emission tomography data (R = 0.79 ± 0.10, N = 8). Furthermore, absolute CBV values quantified by vascular‐space‐occupancy were also in excellent agreement with those by positron emission tomography (slope = 1.00 ± 0.15). Because of the differences in the labeling principles between the two modalities, systematic CBV differences were observed in large vessel and ventricle regions. Magn Reson Med, 2011.