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Homotopy reflects the intrinsic functional architecture of the brain through synchronized spontaneous activity between corresponding bilateral regions, measured as voxel mirrored homotopic connectivity (VMHC). Hypercapnia is known to have clear impact on brain hemodynamics through vasodilation, but have unclear effect on neuronal activity. This study investigates the effect of hypercapnia on brain homotopy, achieved by breathing 5% carbon dioxide (CO2 ) gas mixture. A total of 14 healthy volunteers completed three resting state functional MRI (RS-fMRI) scans, the first and third under normocapnia and the second under hypercapnia. VMHC measures were calculated as the correlation between the BOLD signal of each voxel and its counterpart in the opposite hemisphere. Group analysis was performed between the hypercapnic and normocapnic VMHC maps. VMHC showed a diffused decrease in response to hypercapnia. Significant regional decreases in VMHC were observed in all anatomical lobes, except for the occipital lobe, in the following functional hierarchical subdivisions: the primary sensory-motor, unimodal, heteromodal, paralimbic, as well as in the following functional networks: ventral attention, somatomotor, default frontoparietal, and dorsal attention. Our observation that brain homotopy in RS-fMRI is affected by arterial CO2 levels suggests that caution should be used when comparing RS-fMRI data between healthy controls and patients with pulmonary diseases and unusual respiratory patterns such as sleep apnea or chronic obstructive pulmonary disease., (Copyright © 2015 Wiley Periodicals, Inc.)

Purpose: The calibratable relationship between blood oxygenation (Y) and T(2) allows quantification of cerebral venous oxygenation. We aim to establish a calibration plot between blood T(2) , Y, and hematocrit at 7 T, and using T(2) -relaxation-under-spin-tagging MRI, determine human venous blood oxygenation in vivo., Methods: In vitro experiments were performed at 7 T on bovine blood samples using a Carr-Purcell-Meiboom-Gill-T2 sequence, from which we characterized the relationship among T(2) , Y, and hematocrit. T(2) -relaxation-under-spin-tagging MRI was implemented at 7 T to measure venous blood T2 in vivo, from which oxygenation was estimated using the in vitro calibration plot. Hyperoxia was performed to test the sensitivity of the method to oxygenation changes, and the 7 T results were compared with those at 3 T., Results: In vitro data showed that arterial and venous T(2) at 7 T are 68 and 20 ms, respectively, at a typical hematocrit of 0.42. In vivo measurement showed a cerebral venous oxygenation of 64.7 ± 5.0% and a test-retest coefficient-of-variation of 3.6 ± 2.4%. Hyperoxia increased Yv by 9.0 ± 1.4% (P = 0.001) and the 3 and 7 T results showed a strong correlation (R = 0.95) across individuals., Conclusion: We provided an in vitro calibration plot for conversion of blood T(2) to oxygenation at 7 T and demonstrated its utility in vivo., (Copyright © 2013 Wiley Periodicals, Inc.)

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) (three females, age = 72.4 ± 5.6 years, endurance training >15 years), 12 sedentary elderly (SE) similar in age and educational level (four females, age = 74.6 ± 4.3 years), and nine young controls (YC) (four females, age = 27.2 ± 3.6 years) participated. T1-weighted high-resolution (1 × 1 × 1mm(3) ) 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 MA and two SE were unable to complete the magnetic resonance imaging (MRI) study. Both SE and MA showed lower gray matter (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 white matter (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 subgyral, 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., (Copyright © 2013 Wiley Periodicals, Inc.)

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., (Copyright © 2013 Elsevier Inc. All rights reserved.)

A T(2) -relaxation-under-spin-tagging technique was recently developed to estimate cerebral blood oxygenation, providing potentials for noninvasive assessment of the brain's 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 R(2). This study proposes a postsaturation T(2)-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 T(2)-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)., (Copyright © 2011 Wiley Periodicals, Inc.)

Pseudo-continuous arterial spin labeling (PCASL) MRI is a relatively new arterial spin labeling technique and has the potential to extend the cerebral blood flow (CBF) measurement to all tissue types, including white matter. However, the arterial transit time (δ(a)) for white matter is not well established and a limited number of reports using multi-delay methods have yielded inconsistent findings. In this study, we used a different approach and measured white matter δ(a) (mean ± standard deviation, 1541 ± 173  ms) by determining the arrival times of exogenous contrast agent in a bolus tracking experiment. The data also confirmed δ(a) of gray matter to be 912 ± 209  ms. In the second part of this study, we used these parameters in PCASL kinetic models and compared relative CBF (rCBF, with respect to the whole brain) maps with those measured using a single photon emission computed tomography (SPECT) technique. It was found that the use of tissue-specific δ(a) in the PCASL model was helpful in improving the correspondence between the two modalities. On a regional level, the gray/white matter CBF ratios were 2.47 ± 0.39 and 2.44 ± 0.18 for PCASL and SPECT, respectively. On a single-voxel level, the variance between the modalities was still considerable, with an average rCBF difference of 0.27., (Copyright © 2011 John Wiley & Sons, Ltd.)

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 matter's 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., (Copyright © 2011 Elsevier Inc. All rights reserved.)

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 Alzheimer's 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., (Copyright © 2010 Wiley-Liss, Inc.)

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 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 CO(2) inhalation.

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., (© 2010 Wiley-Liss, Inc.)

A vascular component is increasingly recognized as important in Alzheimer's disease (AD). We measured cerebral blood volume (CBV) in patients with probable AD or Mild Cognitive Impairment (MCI) and in elderly non-demented subjects using a recently developed Vascular-Space-Occupancy (VASO) MRI technique. While both gray and white matters were examined, significant CBV deficit regions were primarily located in white matter, specifically in frontal and parietal lobes, in which CBV was reduced by 20% in the AD/MCI group. The regions with CBV deficit also showed reduced tissue structural integrity as indicated by increased apparent diffusion coefficients, whereas in regions without CBV deficits no such correlation was found. Subjects with lower CBV tended to have more white matter lesions in FLAIR MRI images and showed slower psychomotor speed. These data suggest that the vascular contribution in AD is primarily localized to frontal/parietal white matter and is associated with brain tissue integrity., (Copyright © 2008 Elsevier Inc. All rights reserved.)

Purpose: To characterize multiple patterns of vascular changes in leukoaraiosis using in vivo magnetic resonance imaging (MRI) techniques., Materials and Methods: We measured cerebral blood flow (CBF), cerebrovascular reactivity (CVR), and blood-brain-barrier (BBB) leakage in a group of 33 elderly subjects (age: 72.3 +/- 6.8 years, 17 males, 16 females). Leukoaraiosis brain regions were identified in each subject using fluid-attenuated inversion-recovery (FLAIR) MRI. Vascular parameters in the leukoaraiosis regions were compared to those in the normal-appearing white matter (NAWM) regions. Vascular changes in leukoaraiosis were also compared to structural damage as assessed by diffusion tensor imaging., Results: CBF and CVR in leukoaraiosis regions were found to be 39.7 +/- 5.2% (P < 0.001) and 52.5 +/- 11.6% (P = 0.005), respectively, of those in NAWM. In subjects who did not have significant leukoaraiosis, CBF and CVR in regions with high risk for leukoaraiosis showed a slight reduction compared to the other white matter regions. Significant BBB leakage was also detected (P = 0.003) in leukoaraiosis and the extent of BBB leakage was positively correlated with mean diffusivity. In addition, CVR in NAWM was lower than that in white matter of subjects without significant leukoaraiosis., Conclusion: Leukoaraiosis was characterized by reduced CBF, CVR, and a leakage in the BBB., ((c) 2010 Wiley-Liss, Inc.)

Recently, a vascular-space-occupancy (VASO) MRI technique was developed for quantitative assessment of cerebral blood volume (CBV). This method uses the T(1)-shortening effect of gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA) with imaging parameters chosen that null the precontrast blood magnetization but allow the postcontrast blood magnetization to recover to equilibrium. A key advantage of VASO CBV estimation is that it provides a straightforward procedure for converting MR signals to absolute physiologic values. However, as with other T(1)-based steady-state approaches, several important factors need to be considered that influence the accuracy of CBV values obtained with VASO MRI. Here, the transverse relaxation (T(2)/T(2) (*)) effect in VASO MRI was investigated using multiecho spin-echo and gradient-echo experiments, resulting in underestimation of CBV by 14.9% +/- 1.1% and 16.0% +/- 2.5% for spin echo (TE = 10 ms) and gradient echo (TE = 6 ms), respectively. In addition, the influence of contrast agent clearance was studied by acquiring multiple postcontrast VASO images at 2.2-min intervals, which showed that the concentration of Gd-DTPA in the first 14 min (single dose) was sufficient for the blood magnetization to fully recover to equilibrium. Finally, the effect of vascular Gd-DTPA leakage was assessed for scalp tissue, and signal extrapolation as a function of postinjection time was demonstrated to be useful in minimizing the associated errors. Specific recommendations for VASO MRI acquisition and processing strategies are provided.