Quantification of venous vessel size in human brain in response to hypercapnia and hyperoxia using magnetic resonance imaging.

Hypercapnia and hyperoxia give rise to vasodilation and vasoconstriction, respectively. This study investigates the influence of hypercapnia and hyperoxia on venous vessel size in the human brain. Venous vessel radii were measured in response to hypercapnia and hyperoxia. The venous vessel radii were determined by calculation of the changes in R2 * and R2 that are induced by breathing 6% CO2 or pure oxygen. The experimental paradigm consisted of two 3-min intervals of inhaling 6% CO2 or 100% O2 interleaved with three 2-min intervals of breathing air. Hypercapnic and hyperoxic experiments were performed on eight subjects on a 3T scanner. Parametric maps of mean venous vessel radius were calculated from the changes in R2 * and R2 , which were measured by simultaneous acquisition of gradient-echo and spin-echo signals. The mean venous vessel radii in hypercapnia were 7.3±0.3 µm in gray matter and 6.6±0.5 µm in white matter. The corresponding vessel radii in hyperoxia were 5.6±0.2 µm in gray matter and 5.4±0.2 µm in white matter. These results show that the venous vessel radius was larger in hypercapnia than that in hyperoxia in both gray matter and white matter (P<0.005), which agrees with the hypothesis that hypercapnia causes vasodilation and hyperoxia induces vasoconstriction.

Gray matter nulled and vascular space occupancy dependent fMRI response to visual stimulation during hypoxic hypoxia.

Two cerebral blood volume (CBV)-weighted fMRI techniques, gray matter nulled (GMN) and vascular space occupancy (VASO)-dependent techniques at spatial resolution of 2 × 2 × 5 mm(3), were compared in the study investigating functional responses in the human visual cortex to stimulation in normoxia (inspired O(2) = 21%) and mild hypoxic hypoxia (inspired O(2) = 12%). GMN and VASO signals and T(2)* were quantified in activated voxels. While the CBV-weighted signal changes in voxels activated by visual stimulation were similar in amplitude in both fMRI techniques in both oxygenation conditions, the number of activated voxels during hypoxic hypoxia was significantly reduced by 72 ± 22% in GMN fMRI and 66 ± 23% in VASO fMRI. T(2)* prolonged in GMN and VASO activated voxels in normoxia by 1.6 ± 0.5 ms and 1.7 ± 0.5 ms, respectively. In hypoxia, however, T(2)* shortened in GMN-activated voxels by 0.7 ± 0.6 ms (p < 0.001 relative to normoxia), but prolonged in VASO-activated ones by 1.1 ± 0.6 ms (p < 0.05 relative to normoxia). The data show that the hemodynamic responses to visual stimulation were not affected by hypoxic hypoxia, but T(2)* increases by both CBV-weighted fMRI techniques were smaller in activated voxels in hypoxia. The mechanisms influencing GMN fMRI signal in both oxygenation conditions were explored by simulating effects of the oxygen extraction fraction (OEF) and partial voluming with cerebral spinal fluid (CSF) and white matter in imaging voxels. It is concluded that while GMN fMRI data point to increased, rather than decreased OEF during visual stimulation in hypoxia, partial voluming by CSF is likely to affect the CBV quantification by GMN fMRI under the experimental conditions used.

Magnetic resonance imaging of the mean venous vessel size in the human brain using transient hyperoxia.

Vessel size imaging is an emerging magnetic resonance imaging (MRI) technique which has been demonstrated to provide clinically relevant information about microvascular morphology. While previous studies of vessel size in humans relied on MRI contrast agents or hypercapnia-induced changes in blood oxygenation, the technique described here uses transient hyperoxia to alter the venous blood oxygenation. The experimental paradigm consisted of two 3-minute intervals of breathing 100% O(2) interleaved with three 2-minute intervals of breathing room air. Parametric maps of the mean venous vessel radius were calculated from changes in the blood oxygenation level dependent (BOLD) contrast which were measured using a combined spin-echo (SE) and gradient echo (GE) echo-planar imaging (EPI) sequence. The corresponding mean values in grey and white matter were r=6.5±0.3 µm and r=6.2±0.3 µm (n=6). While the hypercapnia technique requires a specialised gas mixture containing a low concentration of CO(2) (typically 5-6%), the hyperoxia technique presented here uses the inhalation of medical oxygen (100% O(2)) which is routinely available in a clinical environment. Furthermore, 100% O(2) is generally better tolerated than low doses of CO(2) which makes this technique particularly suitable for applications in critically ill patients.

A functional magnetic resonance imaging technique based on nulling extravascular gray matter signal.

A new functional magnetic resonance imaging (fMRI) technique is proposed based on nulling the extravascular gray matter (GM) signal, using a spatially nonselective inversion pulse. The remaining MR signal provides cerebral blood volume (CBV) information from brain activation. A theoretical framework is provided to characterize the sources of GM-nulled (GMN) fMRI signal, effects of partial voluming of cerebrospinal fluid (CSF) and white matter, and behaviors of GMN fMRI signal during brain activation. Visual stimulation paradigm was used to explore the GMN fMRI signal behavior in the human brain at 3T. It is shown that the GMN fMRI signal increases by 7.2%+/-1.5%, which is two to three times more than that obtained with vascular space occupancy (VASO)-dependent fMRI (-3.2%+/-0.2%) or blood oxygenation level-dependent (BOLD) fMRI (2.9%+/-0.7%), using a TR of 3,000 ms and a resolution of 2 x 2 x 5 mm(3). Under these conditions the fMRI signal-to-noise ratio (SNR(fMRI)) for BOLD, GMN, and VASO images was 4.97+/-0.76, 4.56+/-0.86, and 2.43+/-1.06, respectively. Our study shows that both signal intensity and activation volume in GMN fMRI depend on spatial resolution because of partial voluming from CSF. It is shown that GMN fMRI is a convenient tool to assess CBV changes associated with brain activation.

The BOLD response and vascular reactivity during visual stimulation in the presence of hypoxic hypoxia.

A disproportionate increase in cerebral blood flow (CBF) relative to the cerebral metabolic rate of oxygen (CMRO(2)), in response to neuronal activation, results in a decreased oxygen extraction fraction (OEF) and hence local 'hyperoxygenation'. The mismatch is the key 'physiological substrate' for blood oxygenation level dependent (BOLD) fMRI. The mismatch may reflect inefficient O(2) diffusion in the brain tissue, a factor requiring maintenance of a steep [O(2)] gradient between capillary bed and neural cell mitochondria. The aim of this study was to assess vascular responsiveness to reduced blood oxygen saturation, using both BOLD fMRI and the CBV-weighted vascular space occupancy (VASO)-dependent fMRI technique, during visual activation in hypoxic hypoxia. Our fMRI results show decreased amplitude and absence of initial sharp overshoot in the BOLD response, while VASO signal was not influenced by decreasing oxygen saturation down to 0.85. The results suggest that the OEF during visual activation may be different in hypoxia relative to normoxia, due to a more efficient oxygen extraction under compromised oxygen availability. The data also indicate that vascular reactivity to brain activation is not affected by mild hypoxia.

Correlations between MRS and DTI in cerebral small vessel disease.

Cerebral small vessel disease results in lacunar infarcts and cognitive impairment. Diffusion tensor imaging (DTI) demonstrates a reduction in fractional anisotropy and increase in mean diffusivity, which correlates more strongly with cognition than conventional MRI. The underlying pathological basis for these DTI changes is not known. In this study magnetic resonance spectroscopy was used to determine the biochemical basis of these DTI alterations. Twenty-five patients with lacunar stroke and radiological leukoaraiosis were recruited. Chemical shift imaging (CSI) and DTI were performed on a 1.5 T MRI scanner. A region of interest was positioned in the white matter of the centrum semiovale. Multivoxel CSI data were processed and the metabolite ratios estimated. DTI parameters corresponding to the exact region of tissue excited by CSI were obtained. Mean spectroscopy data and DTI values for each subject were correlated. Univariate analysis revealed a positive correlation between N-acetyl aspartate-creatine (NAA/Cr) and fractional anisotropy (r = 0.52, p = 0.008), and a negative correlation with mean diffusivity (r = -0.51, p = 0.009). Results remained little changed after controlling for mean percentage lesion and mean percentage white matter per voxel (with fractional anisotropy r = 0.54, p = 0.008, and with mean diffusivity r = -0.52, p = 0.01). These findings are consistent with axonal loss or dysfunction, or both, accounting for at least part of the DTI abnormalities found in patients with small vessel disease. It provides evidence that DTI identifies axonal disruption in white matter tracts.

Reduced fractional anisotropy on diffusion tensor magnetic resonance imaging after hypoxic-ischemic encephalopathy.

OBJECTIVE: Apparent diffusion coefficients (ADC) that are measured by diffusion-weighted imaging are reduced in severe white matter (WM) and in some severe basal ganglia and thalamic (BGT) injury in infants who present with hypoxic-ischemic encephalopathy (HIE). However, ADC values may pseudonormalize or even be high during this time in some less severe but clinically significant injuries. We hypothesized that fractional anisotropy (FA), a measure of the directional diffusivity of water made using diffusion tensor imaging, may be abnormal in these less severe injuries; therefore, the objective of this study was to use diffusion tensor imaging to measure ADC and FA in infants with moderate and severe hypoxic-ischemic brain injury. METHODS: Twenty infants with HIE and 7 normal control infants were studied. All infants were born at >36 weeks' gestational age, and MRI scans were obtained within 3 weeks of delivery. Data were examined for normality, and comparisons were made using analysis of variance or Kruskal-Wallis as appropriate. RESULTS: During the first week, FA values were decreased with both severe and moderate WM and BGT injury as assessed by conventional imaging, whereas ADC values were reduced only in severe WM injury and some severe BGT injury. Abnormal ADC values pseudonormalized during the second week, whereas FA values continued to decrease. CONCLUSION: FA is reduced in moderate brain injury after HIE. A low FA may reflect a breakdown in WM organization. Moderate BGT injury may result in atrophy but not overt infarction; it is possible that delayed apoptosis is more marked than immediate necrosis, and this may account for normal early ADC values. The accompanying low FA within some severe and all moderate gray matter lesions, which is associated with significant later impairment, may help to confirm clinically significant abnormality in infants with normal ADC values.

Axial and radial diffusivity in preterm infants who have diffuse white matter changes on magnetic resonance imaging at term-equivalent age.

OBJECTIVE: Diffuse excessive high signal intensity (DEHSI) is observed in the majority of preterm infants at term-equivalent age on conventional MRI, and diffusion-weighted imaging has shown that apparent diffusion coefficient values are elevated in the white matter (WM) in DEHSI. Our aim was to obtain diffusion tensor imaging on preterm infants at term-equivalent age and term control infants to test the hypothesis that radial diffusivity was significantly different in the WM in preterm infants with DEHSI compared with both preterm infants with normal-appearing WM on conventional MRI and term control infants. METHODS: Diffusion tensor imaging was obtained on 38 preterm infants at term-equivalent age and 8 term control infants. Values for axial (lambda1) and radial [(lambda2 + lambda3)/2] diffusivity were calculated in regions of interest positioned in the central WM at the level of the centrum semiovale, frontal WM, posterior periventricular WM, occipital WM, anterior and posterior portions of the posterior limb of the internal capsule, and the genu and splenium of the corpus callosum. RESULTS: Radial diffusivity was elevated significantly in the posterior portion of the posterior limb of the internal capsule and the splenium of the corpus callosum, and both axial and radial diffusivity were elevated significantly in the WM at the level of the centrum semiovale, the frontal WM, the periventricular WM, and the occipital WM in preterm infants with DEHSI compared with preterm infants with normal-appearing WM and term control infants. There was no significant difference between term control infants and preterm infants with normal-appearing WM in any region studied. CONCLUSIONS: These findings suggest that DEHSI represents an oligodendrocyte and/or axonal abnormality that is widespread throughout the cerebral WM.

Correction of high-order eddy current induced geometric distortion in diffusion-weighted echo-planar images.

Diffusion-weighted images acquired with the echo-planar imaging technique are highly sensitive to eddy current induced geometric distortions that vary with the magnitude and direction of the diffusion sensitizing gradients. Such distortions cause misalignment of images acquired with different diffusion strengths and orientations. This in turn can result in errors when calculating maps of the apparent diffusion coefficient and diffusion tensor. Previous correction methods either require separate calibration data or only deal with low-order errors. In this study, we demonstrate a method that can correct for higher-order errors. The method relies on collecting pairs of images with diffusion sensitizing gradients reversed. This paired data are first corrected for shifts and linear distortion and then combined to cancel higher-order errors. All acquired data contribute to the final results. The method has been tested by simulation, on phantoms, on adult volunteers, and on neonatal brain examinations.

Effects of random vibration in high-speed phase-shifting speckle pattern interferometry.

The influence of random vibrations on the performance of a dynamic phase-shifting speckle pattern interferometer is investigated by means of experiments and numerical simulations. Two aspects are evaluated: first, temporal unwrapping reliability, second, vibration-induced phase noise. The former is found to be a significant constraint, even for peak velocities well below the Nyquist velocity limit of the interferometer. Shorter sampling windows and higher framing rates are shown to increase the unwrapping success rate, but longer windows reduce the phase error. Three analytical criteria for determining the expected unwrapping success rate are proposed and compared.

Real-time speckle interferometry fringe formation with an adaptive phase mask.

We describe what we believe is a novel speckle-pattern interferometry method of applying a spatial light modulator (SLM) as an adaptive phase mask to obtain real-time fringes of a deformed object without using conventional correlation methods of electronic subtraction or addition. The method is to use a SLM to cancel initial phase in the speckled image before the object is deformed. The fringes from the deformed object can be visualized directly after the initial phase has been canceled. A commercial liquid-crystal television is used as a SLM. The performance of using this SLM in an out-of-plane speckle interferometer is demonstrated.