. Significance: High density diffuse optical tomography (HD-DOT) as applied in functional near-infrared spectroscopy (fNIRS) is largely limited to continuous wave (CW) data. Using a single modulation frequency, frequency domain (FD) HD-DOT has recently demonstrated better localization of focal activation as compared to CW data. We show that combining CW and FD measurements and multiple modulation frequencies increases imaging performance in fNIRS. Aim: We evaluate the benefits of multiple modulation frequencies, combining different frequencies as well as CW data in fNIRS HD-DOT. Approach: A layered model was used, with activation occurring within a cortex layer. CW and FD measurements were simulated at 78, 141, and 203 MHz with and without noise. The localization error, full width half maximum, and effective resolution were evaluated. Results: Across the average of the three metrics, at 141 MHz, FD performed 8.4% better than CW, and the combination of CW and FD was 21.7% better than CW. FD measurements at 203 MHz performed 5% better than 78 MHz. Moreover, the three combined modulation frequencies of FD and CW performed up to 3.92% better than 141 MHz alone. Conclusions: We show that combining CW and FD measurements offers better performance than FD alone, with higher modulation frequencies increasing accuracy. Combining CW and FD measurements at multiple modulation frequencies yields the best overall performance.

Frequency domain (FD) high density diffuse optical tomography (HD-DOT) utilising varying or combined modulation frequencies (mFD) has shown to theoretically improve the imaging accuracy as compared to conventional continuous wave (CW) measurements. Using intensity and phase data from a solid inhomogeneous phantom (NEUROPT) with three insertable rods containing different contrast anomalies, at modulation frequencies of 78 MHz, 141 MHz and 203 MHz, HD-DOT is applied and quantitatively evaluated, showing that mFD outperforms FD and CW for both absolute (iterative) and temporal (linear) tomographic imaging. The localization error (LOCA), full width half maximum (FWHM) and effective resolution (ERES) were evaluated. Across all rods, the LOCA of mFD was 61.3% better than FD and 106.1% better than CW. For FWHM, CW was 6.0% better than FD and mFD and for ERES, mFD was 1.20% better than FD and 9.83% better than CW. Using mFD data is shown to minimize the effect of inherently noisier FD phase data whilst maximising its strengths through improved contrast.

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