Quantitative spatial comparison of diffuse optical imaging with blood oxygen level-dependent and arterial spin labeling-based functional magnetic resonance imaging

Abstract

Akin to functional magnetic resonance imaging (fMRI), diffuse optical imaging (DOI) is a noninvasive method for measuring localized changes in hemoglobin levels within the brain. When combined with fMRI methods, multimodality approaches could offer an integrated perspective on the biophysics, anatomy, and physiology underlying each of the imaging modalities. Vital to the correct interpretation of such studies, control experiments to test the consistency of both modalities must be performed. Here, we compare DOI with blood oxygen level-dependent (BOLD) and arterial spin labeling fMRI-based methods in order to explore the spatial agreement of the response amplitudes recorded by these two methods. Rather than creating optical images by regularized, tomographic reconstructions, we project the fMRI image into optical measurement space using the optical forward problem. We report statistically better spatial correlation between the fMRI-BOLD response and the optically measured deoxyhemoglobin (R=0.71, p=1x10(-7)) than between the BOLD and oxyhemoglobin or total hemoglobin measures (R=0.38, p=0.04|0.37, p=0.05, respectively). Similarly, we find that the correlation between the ASL measured blood flow and optically measured total and oxyhemoglobin is stronger (R=0.73, p=5x10(-6) and R=0.71, p=9x10(-6), respectively) than the flow to deoxyhemoglobin spatial correlation (R=0.26, p=0.10).

Fig. 1

Here we show the probe design and placement for DOI measurements. This probe consisted of eight detector positions (most medial and lateral rows) and four source positions (middle row). The source-detector separation was 2.9 cm. This probe was positioned approximately over the subject's contralateral primary motor cortex as the subject lay in the MRI scanner. The probe also contains vitamin E rings placed on the caps of the optodes, which allowed registration of the optode array in the MR structural image.

Fig. 2

Functional and structural data was processed through several stages before comparison between DOI and fMRI. During the experimental session, anatomical and functional MRI scans were preformed along with the simulations optical imaging. The anatomical images were registered and segmented into a five-layered model (skin, skull, CSF, and gray and white matter). This was used to perform Monte Carlo simulations to determine the light propagation through the head and estimate path-length factors. These forward models were then used to project the functional MRI data into the same source-detector measurement space as the optical data.

Fig. 3

Monte Carlo simulations were used to generate the optical sensitivity profiles for each source and detector pair. A representative profile is shown here overlaying the anatomical volume (subject B). This image is shown in logarithmic scale and contours are presented for each order of magnitude. The inset at the top right shows the location of this coronal slice relative to the optical probe. To show the location of the activation, the t map for the BOLD signal (masked at half maximum) is shown overlaying the anatomical volume. The forward modeling of the BOLD signal involves the multiplication of the BOLD activation and the sensitivity matrix (A). This is equivalent to the sensitivity-weighted sum over the volume of the BOLD contrast changes.

Fig. 4

Following the processing stream outlined in Fig. 2, BOLD data was projected through the simulated optical sensitivity (forward) matrices to produce predicted spatiotemporal profiles of the response across the optical probe. Shown above, correspondence was seen between the response predicted from the BOLD-fMRI data and the measured optical HbR response. The DOI and BOLD time courses above have been normalized to the single maximum response to allow comparisons of the amplitudes across the probe. The HbR time courses have been inverted for this comparison.

Fig. 5

In order to better investigate the spatial correlation between the time course shown in Fig. 4, the mean response amplitude of the period of 3 to 9 seconds was calculated for each source-detector pair. Shown as bar graphs above, the amplitude variation across the probe was coincident between the two modalities.

Fig. 6

Similar to the data presented in Fig. 4, ASL data was projected through the simulated optical sensitivity (forward) matrices to produce predicted spatiotemporal profiles of the response across the optical probe. Shown above, correspondence was seen between the response predicted from the ASL-fMRI data and the measured optical HbT response. The DOI and ASL time courses above have been normalized to the single maximum response to allow comparisons of the amplitudes across the probe.

Fig. 7

The maximum response amplitude was calculated from the optically measured HbT and ASL data for each source-detector pair. Shown as bar graphs above, the amplitude variation across the probe was coincident between the two modalities.

Fig. 8

Although both fMRI methods measure hemodynamic responses, the BOLD and ASL activations were observed to locate to slightly displaced positions in the brain. Shown above is a single axial slice from one of the subjects (F) with both the BOLD and ASL effects maps overlaid. Here the t statistics maps are shown with a half-maximum mask. In both images, crosses mark the positions of the centroids of activation in this slice. The average displacement between the BOLD and ASL maps was 7.0 mm±3.1 mm as shown in Table 4. The approximate location of the optical probe is given as an intensity projection and indicated in dotted circles overlaying these images.

Fig. 9

Using the fMRI following projection by the simulated optical forward matrices, region-of-interest average time courses were calculated from the average of all source-detector pairs. The relative amplitudes have not been rescaled following averaging such that response amplitudes within each comparison are comparable.