title: Near infrared spectroscopy--investigations in neurovascular diseases.
abstract: The purpose of this thesis was to explore and develop methods, where continuous wave near infrared spectroscopy (CW-NIRS) can be applied in different neurovascular diseases, in order to find biological markers that are useful in clinical neurology. To develop a new method to detect changes in cerebral blood flow (CBF), the first study investigated a multi-source detector separation configuration and indocyanine green (ICG) as a tracer to calculate a corrected blood flow index (BFI) value. The study showed no correlation between CBF changes measured by 133Xenon single photon emission computer tomography (133Xe-SPECT) and the corrected BFI value. It was concluded, that it was not possible to obtain reliable BFI data with the ICG CW-NIRS method. NIRS measurements of low frequency oscillations (LFOs) may be a reliable method to investigate vascular alterations in neurovascular diseases, but this requires an acceptable LFOs variation between hemispheres and over time in the healthy brain. The second study therefore investigated day-to-day and hemispheric variations in LFOs with NIRS. It was shown that NIRS might be useful in assessing LFOs between hemispheres, as well as interhemispheric phase and gain directly and over time. Migraine may be associated with persistent impairment of neurovascular coupling, but there is no experimental evidence to support this. The third study therefore investigated interictal neurovascular coupling during a mental task by a Stroop test in migraine without aura (MO) patients, which is the most common type of migraine. The study showed intact neurovascular coupling in the prefrontal cortex outside of attacks in patients with MO. The fourth study aimed to investigate possible changes in LFOs amplitude following nitric oxide (NO) donor infusion in familial hemiplegic migraine (FHM), which is a rare Mendelian subtype of migraine with aura. This study showed increased LFOs amplitude only in FHM patients with co-existing common type of migraine, but not in patients with pure FHM phenotype. This suggests that the sensitivity to NO resides within the common migraine phenotypes rather than the FHM phenotype. Stimulation of the sphenopalatine ganglion (SPG) may lead to parasympathetic outflow and cause pain in cluster headache (CH). The fifth study therefore investigated pain and autonomic symptoms in relation to high or low SPG frequency stimulation in chronic CH patients. Cortical changes in oxygenated hemoglobin (HbO) were also recorded with NIRS and showed a moderate HbO increase, which was most pronounced on the ipsilateral CH side following high frequency stimulation. A possible application of NIRS to assess cerebral vascular changes due to sympathetic activity was investigated in obstructive sleep apnoea (OSA) patients, who have increased sympathetic activity and risk of stroke. Following successful continuous positive airway pressure (CPAP) therapy, OSA patients decreased their LFOs amplitude, which was interpreted as a marker of decreased sympathetic activity in cortical vessels. Finally, a novel hybrid technique, combining NIRS and ultrasound, was tested to detect CBF changes after acetazolamide injection in healthy volunteers using a cerebral flow index (CFI). The study showed an increase in CFI, which correlated with CBF measured with 133Xe-SPECT at 15 min. but not 60 min. Further methodological and explorative clinical studies are needed to assess the feasibility of ultrasound-tagged NIRS in clinical neurology. In summary, the thesis presents several novel approaches, by which NIRS may be used in clinical neurology, and potentials of NIRS to investigate complex mechanisms in neurovascular diseases.
authors.affiliation: henrikschytz@hotmail.com.
authors.forename: Henrik Winther
authors.initials: HW
authors.lastname: Schytz
mesh_terms: D000086:Acetazolamide; D000328:Adult; D001921:Brain / Q000378:metabolism; D002560:Cerebrovascular Circulation / Q000502:physiology*; D002561:Cerebrovascular Disorders / Q000503:physiopathology*; D054022:Cerebrum / Q000503:physiopathology; D003027:Cluster Headache / Q000503:physiopathology; D005260:Female; D006801:Humans; D007208:Indocyanine Green; D008297:Male; D020325:Migraine with Aura / Q000235:genetics / Q000503:physiopathology; D020326:Migraine without Aura / Q000235:genetics / Q000503:physiopathology; D000069336:Neurovascular Coupling / Q000502:physiology; D020030:Nitric Oxide Donors; D010641:Phenotype; D017397:Prefrontal Cortex / Q000503:physiopathology; D020181:Sleep Apnea, Obstructive / Q000503:physiopathology; D019265:Spectroscopy, Near-Infrared / Q000379:methods*; D057190:Stroop Test; D013564:Sympathetic Nervous System / Q000503:physiopathology; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods
chemical_list: D020030:Nitric Oxide Donors; D007208:Indocyanine Green; D000086:Acetazolamide