Dependence of the MR signal on the magnetic susceptibility of blood studied with models based on real microvascular networks.

PURPOSE: The primary goal of this study was to estimate the value of ß , the exponent in the power law relating changes of the transverse relaxation rate and intra-extravascular local magnetic susceptibility differences as ΔR2∗∝(Δχ)ß . The secondary objective was to evaluate any differences that might exist in the value of ß obtained using a deoxyhemoglobin-weighted Δχ distribution versus a constant Δχ distribution assumed in earlier computations. The third objective was to estimate the value of ß that is relevant for methods based on susceptibility contrast agents with a concentration of Δχ higher than that used for BOLD fMRI calculations. METHODS: Our recently developed model of real microvascular anatomical networks is used to extend the original simplified Monte-Carlo simulations to compute ß from the first principles. RESULTS: Our results show that ß=1 for most BOLD fMRI measurements of real vascular networks, as opposed to earlier predictions of ß=1 .5 using uniform Δχ distributions. For perfusion or fMRI methods based on contrast agents, which generate larger values for Δχ , ß=1 for B0≤ 9.4 T, whereas at 14 T ß can drop below 1 and the variation across subjects is large, indicating that a lower concentration of contrast agent with a lower value of Δχ is desired for experiments at high B0 . CONCLUSION: These results improve our understanding of the relationship between R2* and the underlying microvascular properties. The findings will help to infer the cerebral metabolic rate of oxygen and cerebral blood volume from BOLD and perfusion MRI, respectively.

Two-photon microscopy of cortical NADH fluorescence intensity changes: correcting contamination from the hemodynamic response.

Quantification of nicotinamide adenine dinucleotide (NADH) changes during functional brain activation and pathological conditions provides critical insight into brain metabolism. Of the different imaging modalities, two-photon laser scanning microscopy (TPLSM) is becoming an important tool for cellular-resolution measurements of NADH changes associated with cellular metabolic changes. However, NADH fluorescence emission is strongly absorbed by hemoglobin. As a result, in vivo measurements are significantly affected by the hemodynamics associated with physiological and pathophysiological manipulations. We model NADH fluorescence excitation and emission in TPLSM imaging based on precise maps of cerebral microvasculature. The effects of hemoglobin optical absorption and optical scattering from red blood cells, changes in blood volume and hemoglobin oxygen saturation, vessel size, and location with respect to imaging location are explored. A simple technique for correcting the measured NADH fluorescence intensity changes is provided, with the utilization of a parallel measurement of a physiologically inert fluorophore. The model is applied to TPLSM measurements of NADH fluorescence intensity changes in rat somatosensory cortex during mild hypoxia and hyperoxia. The general approach of the correction algorithm can be extended to other TPLSM measurements, where changes in the optical properties of the tissue confound physiological measurements, such as the detection of calcium dynamics.

Monte Carlo simulation of the spatial resolution and depth sensitivity of two-dimensional optical imaging of the brain.

Absorption or fluorescence-based two-dimensional (2-D) optical imaging is widely employed in functional brain imaging. The image is a weighted sum of the real signal from the tissue at different depths. This weighting function is defined as "depth sensitivity." Characterizing depth sensitivity and spatial resolution is important to better interpret the functional imaging data. However, due to light scattering and absorption in biological tissues, our knowledge of these is incomplete. We use Monte Carlo simulations to carry out a systematic study of spatial resolution and depth sensitivity for 2-D optical imaging methods with configurations typically encountered in functional brain imaging. We found the following: (i) the spatial resolution is <200 µm for NA≤0.2 or focal plane depth≤300 µm. (ii) More than 97% of the signal comes from the top 500 µm of the tissue. (iii) For activated columns with lateral size larger than spatial resolution, changing numerical aperature (NA) and focal plane depth does not affect depth sensitivity. (iv) For either smaller columns or large columns covered by surface vessels, increasing NA and/or focal plane depth may improve depth sensitivity at deeper layers. Our results provide valuable guidance for the optimization of optical imaging systems and data interpretation.