A major drawback of functional Magnetic Resonance Imaging (fMRI) concerns the lack of detection accuracy of the measured signal. Although this limitation stems in part from the neuro-vascular nature of the fMRI signal, it also reflects particular methodological decisions in the fMRI data analysis pathway. Here we show that the signal detection accuracy of fMRI is affected by the specific way in which whole-brain volumes are created from individually acquired brain slices, and by the method of statistically extracting signals from the sampled data. To address these limitations, we propose a new framework for fMRI data analysis. The new framework creates whole-brain volumes from individual brain slices that are all acquired at the same point in time relative to a presented stimulus. These whole-brain volumes contain minimal temporal distortions, and are available at a high temporal resolution. In addition, statistical signal extraction occurred on the basis of a non-standard time point-by-time point approach. We evaluated the detection accuracy of the extracted signal in the standard and new framework with simulated and real-world fMRI data. The new slice-based data-analytic framework yields greatly improved signal detection accuracy of fMRI signals.