Conventional methods for assessing cerebral blood flow (CBF) are single photon emission computer tomography (SPECT), positron emission tomography (PET), transcranial Doppler and magnetic resonance imaging in humans. The limitations of these methods are that they are expensive, that the access is limited and in addition PET and SPECT expose patients to radiation.
Near-infrared spectroscopy (NIRS) is well established as a non-invasive method of detecting changes in brain total haemoglobin concentration and oxygenation. NIRS provides a unique opportunity for continuous and non-invasive bedside recording of brain oxygenation in patients with stroke [1
] and head injury [3
]. The method is based on the fact that near-infrared light can penetrate biological tissue and is predominantly absorbed by haemoglobin. The NIRS method has an excellent temporal resolution, whereas the spatial resolution is limited depending on the source detector (SD) distance and number of detectors [5
The use of the optical dye indocyanine green (ICG) as an intravascular tracer to measure relative changes in CBF with NIRS has been suggested as an easy, safe and reliable method for serial bedside measurements of relative CBF changes within a subject [7
]. The method is based on monitoring the first passage of an injected ICG bolus through the cerebral vasculature by NIRS and is believed to be a specific indicator of cerebral, not extracerebral, circulation [9
]. The accuracy of the method was confirmed in a piglet model, in which the NIRS blood flow index (BFI), a relative measure of CBF, significantly correlated with the gold standard microspheres technique [9
]. Human studies have shown that repeated measurements of BFI have an acceptable coefficient of variation during baseline recordings [8
]. However, no studies so far have correlated the BFI method to established methods of measuring CBF in humans, such as SPECT or PET.
Furthermore, the vast majority of studies using NIRS measurement of an ICG bolus to estimate CBF were performed using a continuous wave (CW) system and a single SD separation configuration [1
]. This method is known to be impaired by strong contamination of the cerebral signal from superficial tissue layers [13
]. As an alternative to this commonly used configuration, Kohl-Bareis et al.
] used a time-domain NIRS system and Steinbrink et al.
] a frequency-domain NIRS system to track the passage of an ICG bolus in healthy subjects and patients undergoing cardiopulmonary bypass respectively. By measuring the time-of-flight of photons, they were able to get depth-resolved measurements of the bolus time course and therefore to distinguish between extracerebral and intracerebral signals. Furthermore, both studies showed that a conventional single-distance CW analysis would have failed to detect changes in CBF because the contamination by skin blood flow was too high at least in some subjects.
In the present study, we investigate an alternative approach where a simple CW system was used in a multi SD separation configuration. The method uses short SD (1 cm) separation to assess the contribution of skin blood flow, which contaminates the BFI values [13
], and subtracts it from the signal obtained at larger SD (3 cm) separation. To test this method, we collected NIRS and Xe-SPECT data during and after an acetazolamide challenge. We correlated the relative changes found with the BFI method to CBF changes measured by 133