Integrating near-infrared spectroscopy to synchronous multimodal neuroimaging:applications and novel findings

Abstract Brain disorders such as epilepsy, dementia and other mental illnesses induce increasing costs on health care systems with aging populations. The most effective treatment of these disorders would be either prevention or intervention of the disorder before irreversible damage develops. However, despite the increased interest in different brain diseases, many of them are still detected too late. One reason for this is the lack of appropriate functional imaging modality that can critically sample the targeted physiological phenomenon. Furthermore, it has been shown that one imaging modality is not enough to cover brain functionality properly; a multimodal approach is required. The main goal of this thesis was to validate near-infrared spectroscopy (NIRS) for brain measurement and to integrate it into a multimodal neuroimaging setup that can critically sample basic human physiological phenomena. A novel key element was the combined use of NIRS with ultra-fast magnetic resonance encephalography (MREG), electroencephalography (EEG), continuous non-invasive blood pressure and anesthesia monitoring as a synchronous system. This unique multimodal neuroimaging set-up with a new functional magnetic resonance imaging sequence, MREG, can sample human brain physiology at 10 Hz sampling rate without cardiorespiratory aliasing. The implemented setup was successfully used in scanning multiple patient and control populations. With the help of critical sampling rate, non-stationarity between the measured signals reflecting brain pulsations could be detected. Combined NIRS and EEG showed the capability to monitor therapeutic opening of the blood-brain barrier during treatment of central nervous system lymphoma for the first time in humans. Furthermore, our multimodal neuroimaging setup enabled the mapping of the recently described brain avalanches and glymphatic pulsation mechanisms of the brain. In conclusion, the ultra-fast multimodal laboratory with integrated NIRS offers novel and more comprehensive views on basic brain physiology. The measures from this thesis also have the potential to offer new, quantitative biomarkers for the detection of different brain disorders prior to irreversible damage.Tiivistelmä Aivosairaudet kuten epilepsia, dementia ja muut mielenterveyden häiriöt aiheuttavat kasvavissa määrin kuluja ikääntyvien ihmisten terveydenhuollossa. Näiden tautien tehokkain hoitokeino olisi joko ennaltaehkäisy tai varhainen havaitseminen ennen peruuttamattomien kudosvaurioiden kehittymistä. Lisääntyneestä kiinnostuksesta huolimatta monet aivosairaudet havaitaan edelleen liian myöhään. Osasyy tähän on sopivan toiminnallisen kuvausmenetelmän puuttuminen, jolla voitaisiin kuvata haluttu fysiologinen ilmiö riittävän nopeasti. Onkin osoitettu, ettei yksittäinen kuvausmenetelmä riitä aivojen toiminnan riittävän tarkkaan ymmärtämiseen, vaan siihen tarvitaan eri menetelmien yhdistämistä. Tämän väitöskirjatutkimuksen päätarkoituksena oli arvioida lähi-infrapunaspektroskopian (NIRS) soveltuvuutta aivojen toiminnan mittaamisessa sekä integroida se osaksi multimodaalista neurokuvantamisjärjestelmää. Uutena elementtinä NIRS:iä käytettiin yhdessä ultranopean magneettiresonanssienkefalogrammin (MREG), aivosähkökäyrän (EEG), jatkuva-aikaisen kajoamattoman verenpaineen mittauksen ja anestesiamonitoroinnin kanssa samanaikaisesti, ajallisesti synkronoituna. Yhdessä uuden toiminnallisen magneettikuvaussekvenssin, MREG:n, kanssa tällä ainutlaatuisella multimodaalisella neurokuvantamisjärjestelmällä voidaan kuvata ihmisen aivojen perusfysiologiaa 10 Hz näytteistysnopeudella ilman sydämen sykkeen ja hengityksen laskostumista. Toteutetulla multimodaalisella mittausjärjestelmällä tehtiin useita onnistuneita kuvauksia eri potilasryhmillä ja terveillä koehenkilöillä. Kriittisen näytteistämisen ansiosta voitiin havaita epästationaarisuutta aivojen pulsaatioita heijastelevien signaalien välillä. NIRS:n ja EEG:n samanaikainen mittaaminen mahdollisti ensimmäistä kertaa ihmisen veriaivoesteen aukeamisen monitoroinnin keskushermostolymfoomapotilaiden hoidossa. Lisäksi multimodaalinen neurokuvantamisjärjestelmä mahdollisti hiljattain havaittujen aivojen vyöryjen (engl. avalanches) ja glymfaattisten pulsaatioiden kartoittamisen. Yhteenvetona voidaan todeta, että väitöskirjatyön aikana toteutettu multimodaalinen laboratorio yhdessä NIRS:n kanssa mahdollistaa aivojen perusfysiologian edistyksellisen ja tarkan tutkimisen. Nyt kehitetyt mittarit saattavat myös tarjota uusia, kvantitatiivisia biomarkkereita eri aivosairauksiin ennen vakavien vaurioiden syntymistä

Management strategies for aflatoxin risk mitigation in maize, dairy feeds and milk value chains—case study Kenya

202

Fractional amplitude of physiological fluctuations of resting state fNIRS in Alzheimer’s disease patient and healthy control

Abstract Functional magnetic resonance imaging (fMRI) is a common medical device to diagnose Alzheimer’s disease (AD), but it is not for all subjects due to its cost and other issues. We investigated the potential of functional near-infrared spectroscopy (fNIRS) to separate AD patients from controls as a pre-screening prior to more thorough examination using fMRI. For this purpose, two-channel fNIRS device with 690 nm and 830 nm, sampled at 10 Hz, was placed on the forehead with 3 cm distance between light source and detector to provide resting state fNIRS signals from both sides of pre-frontal cortex. We applied fractional amplitude of physiological fluctuation (fAPF), modified from fractional amplitude of low frequency fluctuation (fALFF), to oxy-, deoxy-, and total-hemoglobin in very low frequency (0.008‐0.1 Hz), respiratory (0.1‐0.6 Hz), and cardiac (0.6‐5 Hz) bands. A t-test at 0.05 significance level was used to evaluate if the fAPF score from AD patients and healthy controls is significantly different. We found that fAPF score of total hemoglobin from both side at cardiac band showed its potential to distinguish AD patients from healthy controls. This finding was in-line with the recent finding that heart failure may co-occur in AD patients with the prevalence of one third of cases

Inverse correlation of fluctuations of cerebral blood and water concentrations in humans

Abstract Near-infrared spectroscopy (fNIRS) measures concentrations of oxygenated (HbO) and deoxygenated (HbR) hemoglobin in the brain. Recently, we demonstrated its potential also for measuring concentrations of cerebral water (cH₂O). We performed fNIRS measurements during rest to study fluctuations in concentrations of cH₂O, HbO and HbR in 33 well-rested healthy control subjects (HC) and 18 acutely sleep-deprived HC. Resting-state fNIRS signal was filtered in full-band, cardiac, respiratory, low-, and very-low-frequency bands. The sum of HbO and HbR constitutes the regional cerebral blood volume (CBV). CBV and cH₂O concentrations were analyzed via temporal correlation and phase synchrony. Fluctuation in concentrations of cH₂O and CBV was strongly anti-correlated across all frequency bands in both frontal and parietal cortices. Fluctuation in concentrations of cH₂O and CBV showed neither a completely synchronous nor a random phase relationship in both frontal and parietal cortices. Acutely sleep-deprived subjects did not show significant differences in temporal correlation or phase synchrony between fluctuations in cH₂O and CBV concentrations compared with well-rested HC. The reciprocal interrelation between fluctuations in CBV and cH₂O concentrations is consistent with the Munro–Kellie doctrine of constant intracranial volume. This coupling may constitute a functional mechanism underlying glymphatic circulation, which persists despite acutely disturbed sleep patterns

Increased very low frequency pulsations and decreased cardiorespiratory pulsations suggest altered brain clearance in narcolepsy

Abstract Background: Narcolepsy is a chronic neurological disease characterized by daytime sleep attacks, cataplexy, and fragmented sleep. The disease is hypothesized to arise from destruction or dysfunction of hypothalamic hypocretin-producing cells that innervate wake-promoting systems including the ascending arousal network (AAN), which regulates arousal via release of neurotransmitters like noradrenalin. Brain pulsations are thought to drive intracranial cerebrospinal fluid flow linked to brain metabolite transfer that sustains homeostasis. This flow increases in sleep and is suppressed by noradrenalin in the awake state. Here we tested the hypothesis that narcolepsy is associated with altered brain pulsations, and if these pulsations can differentiate narcolepsy type 1 from healthy controls. Methods: In this case-control study, 23 patients with narcolepsy type 1 (NT1) were imaged with ultrafast fMRI (MREG) along with 23 age- and sex-matched healthy controls (HC). The physiological brain pulsations were quantified as the frequency-wise signal variance. Clinical relevance of the pulsations was investigated with correlation and receiving operating characteristic analysis. Results: We find that variance and fractional variance in the very low frequency (MREGvlf) band are greater in NT1 compared to HC, while cardiac (MREGcard) and respiratory band variances are lower. Interestingly, these pulsations differences are prominent in the AAN region. We further find that fractional variance in MREGvlf shows promise as an effective bi-classification metric (AUC = 81.4%/78.5%), and that disease severity measured with narcolepsy severity score correlates with MREGcard variance (R = −0.48, p = 0.0249). Conclusions: We suggest that our novel results reflect impaired CSF dynamics that may be linked to altered glymphatic circulation in narcolepsy type 1

Multimodal brain imaging with magnetoencephalography:a method for measuring blood pressure and cardiorespiratory oscillations

Abstract Studies with magnetoencephalography (MEG) are still quite rarely combined simultaneously with methods that can provide a metabolic dimension to MEG investigations. In addition, continuous blood pressure measurements which comply with MEG compatibility requirements are lacking. For instance, by combining methods reflecting neurovascular status one could obtain more information on low frequency fluctuations that have recently gained increasing interest as a mediator of functional connectivity within brain networks. This paper presents a multimodal brain imaging setup, capable to non-invasively and continuously measure cerebral hemodynamic, cardiorespiratory and blood pressure oscillations simultaneously with MEG. In the setup, all methods apart from MEG rely on the use of fibre optics. In particular, we present a method for measuring of blood pressure and cardiorespiratory oscillations continuously with MEG. The potential of this type of multimodal setup for brain research is demonstrated by our preliminary studies on human, showing effects of mild hypercapnia, gathered simultaneously with the presented modalities

Respiratory-related brain pulsations are increased in epilepsy:a two-centre functional MRI study

Abstract Resting-state functional MRI has shown potential for detecting changes in cerebral blood oxygen level-dependent signal in patients with epilepsy, even in the absence of epileptiform activity. Furthermore, it has been suggested that coefficient of variation mapping of fast functional MRI signal may provide a powerful tool for the identification of intrinsic brain pulsations in neurological diseases such as dementia, stroke and epilepsy. In this study, we used fast functional MRI sequence (magnetic resonance encephalography) to acquire ten whole-brain images per second. We used the functional MRI data to compare physiological brain pulsations between healthy controls (n = 102) and patients with epilepsy (n = 33) and furthermore to drug-naive seizure patients (n = 9). Analyses were performed by calculating coefficient of variation and spectral power in full band and filtered sub-bands. Brain pulsations in the respiratory-related frequency sub-band (0.11–0.51 Hz) were significantly (P < 0.05) increased in patients with epilepsy, with an increase in both signal variance and power. At the individual level, over 80% of medicated and drug-naive seizure patients exhibited areas of abnormal brain signal power that correlated well with the known clinical diagnosis, while none of the controls showed signs of abnormality with the same threshold. The differences were most apparent in the basal brain structures, respiratory centres of brain stem, midbrain and temporal lobes. Notably, full-band, very low frequency (0.01–0.1 Hz) and cardiovascular (0.8–1.76 Hz) brain pulses showed no differences between groups. This study extends and confirms our previous results of abnormal fast functional MRI signal variance in epilepsy patients. Only respiratory-related brain pulsations were clearly increased with no changes in either physiological cardiorespiratory rates or head motion between the subjects. The regional alterations in brain pulsations suggest that mechanisms driving the cerebrospinal fluid homeostasis may be altered in epilepsy. Magnetic resonance encephalography has both increased sensitivity and high specificity for detecting the increased brain pulsations, particularly in times when other tools for locating epileptogenic areas remain inconclusive

Continuous blood pressure recordings simultaneously with functional brain imaging:studies of the glymphatic system

Abstract The lymph system is responsible for cleaning the tissues of metabolic waste products, soluble proteins and other harmful fluids etc. Lymph flow in the body is driven by body movements and muscle contractions. Moreover, it is indirectly dependent on the cardiovascular system, where the heart beat and blood pressure maintain force of pressure in lymphatic channels. Over the last few years, studies revealed that the brain contains the so-called glymphatic system, which is the counterpart of the systemic lymphatic system in the brain. Similarly, the flow in the glymphatic system is assumed to be mostly driven by physiological pulsations such as cardiovascular pulses. Thus, continuous measurement of blood pressure and heart function simultaneously with functional brain imaging is of great interest, particularly in studies of the glymphatic system. We present our MRI compatible optics based sensing system for continuous blood pressure measurement and show our current results on the effects of blood pressure variations on cerebral brain dynamics, with a focus on the glymphatic system. Blood pressure was measured simultaneously with near-infrared spectroscopy (NIRS) combined with an ultrafast functional brain imaging (fMRI) sequence magnetic resonance encephalography (MREG, 3D brain 10 Hz sampling rate)