Physiological Biomarkers of the Central Nervous System in fMRI

In functional magnetic resonance imaging the primary contrast is blood oxygen level dependent (BOLD) signal, changes of which are caused by a number of factors. Filtering the BOLD signal to the low frequency oscillation (LFO) band (0.01-0.1 Hz) yields the long-term fluctuations in signal from metabolic or systemic changes. A prominent component of the LFO band has been shown to originate from outside the brain, dubbed the systemic LFO (sLFO). Correlating averaged regional sLFO signals acts as an endogenous bolus to track the flow of blood. Shifts between maximal correlation correspond to the relative delay of blood arrival at these regions of interest. This provides a useful and non-invasive method to evaluate blood flow changes.

In Sickle Cell Disease (SCD) this method was used to evaluate the abnormal blood flow common within the condition. In healthy patients, the relationship between the brain and its major venous outflow, the superior sagittal sinus (SSS), was normal with the SSS lagging. However, it was found that in all SCD individuals there was also a leading signal, possibly suggesting two pathways for blood to reach the SSS. These are hypothesized to be a normal pathway through the capillary bed and an alternative shunted pathway wherein blood flow bypasses the capillary bed and highly oxygenated blood reaches the venous system. Novelly, the magnitude of this shunted pathway signal increased with disease severity, implying a novel biomarker for SCD progression.

Similarly, the hemodynamic relationship between the brain and spinal cord, an under-investigated topic, was assessed using sLFO techniques. It was found that the brain-spinal cord relationship is comprised of two distinct signals, one with the spinal cord leading the brain and one with it lagging. The early signal is proposed to be carried by arterial flow, reaching the spinal cord before the brain. The late path is believed to be outflow from the brain via the vertebral venous plexus, a network of veins connecting the lower brain to the cervical spine. This could provide a valuable biomarker for vascular damage in spinal cord injury.