Characterization of the microvascular cerebral blood flow response to obstructive apneic events during night sleep

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Cerebral vasoreactivity in response to a headof-bed position change is altered in patients with moderate and severe obstructive sleep apnea

Obstructive sleep apnea (OSA) can impair cerebral vasoreactivity and is associated with an increased risk of cerebrovascular disease. Unfortunately, an easy-to-use, non-invasive, portable monitor of cerebral vasoreactivity does not exist. Therefore, we have evaluated the use of near-infrared diffuse correlation spectroscopy to measure the microvascular cerebral blood flow (CBF) response to a mild head-of-bed position change as a biomarker for the evaluation of cerebral vasoreactivity alteration due to chronic OSA. Furthermore, we have monitored the effect of two years of continuous positive airway pressure (CPAP) treatment on the cerebral vasoreactivity.Peer ReviewedPostprint (published version

Transcranial diffuse optical assessment of the microvascular reperfusion after thrombolysis for acute ischemic stroke

In this pilot study, we have evaluated bedside diffuse optical monitoring combining diffuse correlation spectroscopy and near-infrared diffuse optical spectroscopy to assess the effect of thrombolysis with an intravenous recombinant tissue plasminogen activator (rtPA) on cerebral hemodynamics in an acute ischemic stroke. Frontal lobes of five patients with an acute middle cerebral artery occlusion were measured bilaterally during rtPA treatment. Both ipsilesional and contralesional hemispheres showed significant increases in cerebral blood flow, total hemoglobin concentration and oxy-hemoglobin concentration during the first 2.5 hours after rtPA bolus. The increases were faster and higher in the ipsilesional hemisphere. The results show that bedside optical monitoring can detect the effect of reperfusion therapy for ischemic stroke in real-time.Peer ReviewedPostprint (published version

Blood flow response to orthostatic challenge identifies signatures of the failure of static cerebral autoregulation in patients with cerebrovascular disease

Autorregulació cerebral; Malaltia cerebrovascular; Òptica difusaAutorregulación cerebral; Enfermedad cerebrovascular; Óptica difusaCerebral autoregulation; Cerebrovascular disease; Diffuse opticsBackground The cortical microvascular cerebral blood flow response (CBF) to different changes in head-of-bed (HOB) position has been shown to be altered in acute ischemic stroke (AIS) by diffuse correlation spectroscopy (DCS) technique. However, the relationship between these relative ΔCBF changes and associated systemic blood pressure changes has not been studied, even though blood pressure is a major driver of cerebral blood flow. Methods Transcranial DCS data from four studies measuring bilateral frontal microvascular cerebral blood flow in healthy controls (n = 15), patients with asymptomatic severe internal carotid artery stenosis (ICA, n = 27), and patients with acute ischemic stroke (AIS, n = 72) were aggregated. DCS-measured CBF was measured in response to a short head-of-bed (HOB) position manipulation protocol (supine/elevated/supine, 5 min at each position). In a sub-group (AIS, n = 26; ICA, n = 14; control, n = 15), mean arterial pressure (MAP) was measured dynamically during the protocol. Results After elevated positioning, DCS CBF returned to baseline supine values in controls (p = 0.890) but not in patients with AIS (9.6% [6.0,13.3], mean 95% CI, p < 0.001) or ICA stenosis (8.6% [3.1,14.0], p = 0.003)). MAP in AIS patients did not return to baseline values (2.6 mmHg [0.5, 4.7], p = 0.018), but in ICA stenosis patients and controls did. Instead ipsilesional but not contralesional CBF was correlated with MAP (AIS 6.0%/mmHg [− 2.4,14.3], p = 0.038; ICA stenosis 11.0%/mmHg [2.4,19.5], p < 0.001). Conclusions The observed associations between ipsilateral CBF and MAP suggest that short HOB position changes may elicit deficits in cerebral autoregulation in cerebrovascular disorders. Additional research is required to further characterize this phenomenon.The funders did not have any role in study design, execution and data interpretation. This work was funded by Redes Temáticas de Investigación Cooperativa (RETICS-INVICTUS RD012/0014 and RD16/0019/0010), Fundació CELLEX Barcelona, Ministerio de Economía y Competitividad/FEDER (PHOTODEMENTIA, PHOTOMETABO, DPI2015–64358-C2–1-R, PRE2018-085082), Instituto de Salud Carlos III/FEDER (FIS PI09/0557, MEDPHOTAGE, DTS16/00087), the “Severo Ochoa” Programme for Centres of Excellence in R&D (SEV-2015-0522), the Obra Social “la Caixa” Foundation (LlumMedBcn), Institució “Centres de Recerca de Catalunya”, “Agència de Gestió d’Ajuts Universitaris i de Recerca”-Generalitat (2017SGR-1380), LASERLAB-EUROPE IV (EU-H2020 654148), Whitaker International Program of the Institute for International Education, T32 HL007954 Multidisciplinary training in cardiovascular biology, Marie Curie initial training network (OILTEBIA 317526), Marie Sklowdowska-Curie-COFUND (H2020, ICFOstepstone 2, 71329), “Fundació La Marató TV3” (201709.30, 201709.31), São Paulo Research Foundation (FAPESP) through 2012/02500–8 and National Institutes of Health (R01-NS060653, K24-NS058386, R24-HD050836, P41-EB015893, DP2-HD101400, U54-HD086984)

Blood flow response to orthostatic challenge identifies signatures of the failure of static cerebral autoregulation in patients with cerebrovascular disease

Background: The cortical microvascular cerebral blood flow response (CBF) to different changes in head-of-bed (HOB) position has been shown to be altered in acute ischemic stroke (AIS) by diffuse correlation spectroscopy (DCS) technique. However, the relationship between these relative ¿CBF changes and associated systemic blood pressure changes has not been studied, even though blood pressure is a major driver of cerebral blood flow. Methods: Transcranial DCS data from four studies measuring bilateral frontal microvascular cerebral blood flow in healthy controls (n = 15), patients with asymptomatic severe internal carotid artery stenosis (ICA, n = 27), and patients with acute ischemic stroke (AIS, n = 72) were aggregated. DCS-measured CBF was measured in response to a short head-of-bed (HOB) position manipulation protocol (supine/elevated/supine, 5 min at each position). In a sub-group (AIS, n = 26; ICA, n = 14; control, n = 15), mean arterial pressure (MAP) was measured dynamically during the protocol. Results: After elevated positioning, DCS CBF returned to baseline supine values in controls (p = 0.890) but not in patients with AIS (9.6% [6.0,13.3], mean 95% CI, p < 0.001) or ICA stenosis (8.6% [3.1,14.0], p = 0.003)). MAP in AIS patients did not return to baseline values (2.6 mmHg [0.5, 4.7], p = 0.018), but in ICA stenosis patients and controls did. Instead ipsilesional but not contralesional CBF was correlated with MAP (AIS 6.0%/mmHg [- 2.4,14.3], p = 0.038; ICA stenosis 11.0%/mmHg [2.4,19.5], p < 0.001). Conclusions: The observed associations between ipsilateral CBF and MAP suggest that short HOB position changes may elicit deficits in cerebral autoregulation in cerebrovascular disorders. Additional research is required to further characterize this phenomenon.Peer ReviewedPostprint (published version

Concurrent measurement of cerebral hemodynamics and electroencephalography during transcranial direct current stimulation

Transcranial direct current stimulation (tDCS) is currently being used for research and treatment of some neurological and neuropsychiatric disorders, as well as for improvement of cognitive functions. In order to better understand cerebral response to the stimulation and to redefine protocols and dosage, its effects must be monitored. To this end, we have used functional diffuse correlation spectroscopy (fDCS) and time-resolved functional near-infrared spectroscopy (TR-fNIRS) together with electroencephalography (EEG) during and after stimulation of the frontal cortex. Twenty subjects participated in two sessions of stimulation with two different polarity montages and twelve also underwent a sham session. Cerebral blood flow and oxyhemoglobin concentration increased during and after active stimulation in the region under the stimulation electrode while deoxyhemoglobin concentration decreased. The EEG spectrum displayed statistically significant power changes across different stimulation sessions in delta (2 to 4 Hz), theta (4 to 8 Hz), and beta (12 to 18 Hz) bands. Results suggest that fDCS and TR-fNIRS can be employed as neuromonitors of the effects of transcranial electrical stimulation and can be used together with EEG.Peer ReviewedPostprint (published version

Cerebral vasoreactivity in response to a head-of-bed position change is altered in patients with moderate and severe obstructive sleep apnea

Obstructive sleep apnea (OSA) can impair cerebral vasoreactivity and is associated with an increased risk of cerebrovascular disease. Unfortunately, an easy-to-use, non-invasive, portable monitor of cerebral vasoreactivity does not exist. Therefore, we have evaluated the use of near-infrared diffuse correlation spectroscopy to measure the microvascular cerebral blood flow (CBF) response to a mild head-of-bed position change as a biomarker for the evaluation of cerebral vasoreactivity alteration due to chronic OSA. Furthermore, we have monitored the effect of two years of continuous positive airway pressure (CPAP) treatment on the cerebral vasoreactivity. CBF was measured at different head-of-bed position changes (supine to 30° to supine) in sixty-eight patients with OSA grouped according to severity (forty moderate to severe, twenty-eight mild) and in fourteen control subjects without OSA. A subgroup (n = 13) with severe OSA was measured again after two years of CPAP treatment. All patients and controls showed a similar CBF response after changing position from supine to 30° (p = 0.819), with a median (confidence interval) change of -17.5 (-10.3, -22.9)%. However, when being tilted back to the supine position, while the control group (p = 0.091) and the mild patients with OSA (p = 0.227) recovered to the initial baseline, patients with moderate and severe OSA did not recover to the baseline (9.8 (0.8,12.9)%, p < 0.001) suggesting altered cerebral vasoreactivity. This alteration was correlated with OSA severity defined by the apnea-hypopnea index, and with mean nocturnal arterial oxygen saturation. The CBF response was normalized after two years of CPAP treatment upon follow-up measurements. In conclusion, microvascular CBF response to a head-of-bed challenge measured by diffuse correlation spectroscopy suggests that moderate and severe patients with OSA have altered cerebral vasoreactivity related to OSA severity. This may normalize after two years of CPAP treatment

Characterization of the microvascular cerebral blood flow response to obstructive apneic events during night sleep

Altres ajuts: This work was funded by the "Severo Ochoa" Programme for Centres of Excellence in R&D (Grant No. SEV-2015-0522), the Obra Social "la Caixa" Foundation (Grant Nos. LlumMedBcn, Programa de Matemàtica Col·laborativa), LASERLABEUROPE IV (Grant No. EU-H2020 654148), Marie Curie initial training network (Grant No. OILTEBIA 317526), Societat Catalana de Pneumologia (SOCAP), and Sociedad Española de Neumología y Cirugía Torácica (SEPAR).Obstructive apnea causes periodic changes in cerebral and systemic hemodynamics, which may contribute to the increased risk of cerebrovascular disease of patients with obstructive sleep apnea (OSA) syndrome. The improved understanding of the consequences of an apneic event on the brain perfusion may improve our knowledge of these consequences and then allow for the development of preventive strategies. Our aim was to characterize the typical microvascular, cortical cerebral blood flow (CBF) changes in an OSA population during an apneic event. Sixteen patients (age , 75% male) with a high risk of severe OSA were measured with a polysomnography device and with diffuse correlation spectroscopy (DCS) during one night of sleep with 1365 obstructive apneic events detected. All patients were later confirmed to suffer from severe OSA syndrome with a mean of apneas and hypopneas per hour. DCS has been shown to be able to characterize the microvascular CBF response to each event with a sufficient contrast-to-noise ratio to reveal its dynamics. It has also revealed that an apnea causes a peak increase of microvascular CBF () at the end of the event followed by a drop () similar to what was observed in macrovascular CBF velocity of the middle cerebral artery. This study paves the way for the utilization of DCS for further studies on these populations

Microvascular cerebral blood flow fluctuations in association with apneas and hypopneas in acute ischemic stroke

Altres ajuts: The authors thank Dr. Arjun Yodh, Dr. John A. Detre, Dr. Janos Lückl, and Rosa Maria Miralda for their useful discussions. They acknowledge the support from Redes Temáticas de Investigación Cooperativa (RETICS-INVICTUS RD012/0014 and RETICS-INVICTUS PLUS RD16/0019/0010), the "Severo Ochoa" Programme for Centres of Excellence in R&D (SEV-2015-0522), the Obra Social "la Caixa" Foundation (LlumMedBcn) LASERLAB-EUROPE IV (EU-H2020 654148), "Fundació La Marató TV3" (201709.31), Marie Curie initial training network (OILTEBIA 317526), Societat Catalana de Pneumologia (SOCAP), and Sociedad Española de Neumología y Cirugía Torácica (SEPAR).In a pilot study on acute ischemic stroke (AIS) patients, unexpected periodic fluctuations in microvascular cerebral blood flow (CBF) had been observed. Motivated by the relative lack of information about the impact of the emergence of breathing disorders in association with stroke on cerebral hemodynamics, we hypothesized that these fluctuations are due to apneic and hypopneic events. A total of 28 patients were screened within the first week after stroke with a pulse oximeter. Five (18%) showed fluctuations of arterial blood oxygen saturation (=3%) and were included in the study. Near-infrared diffuse correlation spectroscopy (DCS) was utilized bilaterally to measure the frontal lobe CBF alongside respiratory polygraphy. Biphasic CBF fluctuations were observed with a bilateral increase of 27.1% 17.7% and 29.0% 17.4% for the ipsilesional and contralesional hemispheres, respectively, and a decrease of -19.3% 9.1% and -21.0% 8.9% for the ipsilesional and contralesional hemispheres, respectively. The polygraph revealed that, in general, the fluctuations were associated with apneic and hypopneic events. This study motivates us to investigate whether the impact of altered respiratory patterns on cerebral hemodynamics can be detrimental in AIS patients

Correlates of cerebral vasoreactivity measured by non-invasive diffuse optical measurements as biomarkers of brain injury risk

Aplicat embargament des de la data de defensa fins a l'11/1/2021I have used and developed a practical new platform in the clinics for the noninvasive estimation of cerebral hemodynamics. The latform combines two diffuse optical techniques: near-infrared spectroscopy and diffuse correlation spectroscopy. To study patients at a high risk of cerebrovascular accidents, and those who have recently suffered an ischemic stroke, several protocols were devised and carried out. This set of multi-disciplinary studies was performed in close collaboration with the Stroke Unit and the Sleep Unit at Hospital de la Santa Creu i Sant Pau (Barcelona, Spain) with the ultimate goal to identify new biomarkers for the assessment of cerebral autoregulation and cerebral vasoreactivity, and, ultimately, cerebral well-being. The bulk of the studies on these patients focused on the investigation of microvascular cerebral physiology in response to a non-invasive and benign challenge, without the need of patient collaboration nor any additional equipment. This challenge involved an alteration of the patient head-of-bed positioning. Interestingly, the head-of-bed challenge with the measurement of microvascular cerebral blood ow has been shown as a potential protocol to tell us about the status of cerebral autoregulation in these patients. This in turn was shown to track impairments over time, and the patients' response to treatments, and to predict long-term outcome. Overall, this thesis pushes the limits of the clinical translation of hybrid diffuse optics, paving the way for new clinical applications at the point-of-care and in the neurocritical care.En aquest treball he utilitzat i desenvolupat una nova plataforma d'ús clínic per a l'estimació no invasiva de l'hemodinàmica de teixits que combina dues tècniques híbrides d'òptica difusa: l'espectroscòpia de l'infraroig proper i l'espectroscòpia de correlació difusa. S'han ideat i dut a terme diferents protocols per estudiar pacients amb un alt risc d'accidents cerebrovasculars i pacients que han patit recentment un accident cerebrovascular isquèmic. Aquest conjunt d'estudis multidisciplinars s'han pogut dur a terme gràcies a l'estreta col·laboració amb la Unitat d'Ictus i la Unitat de Trastorns Respiratoris del Son de l'Hospital de la Santa Creu i Sant Pau (Barcelona, Espanya), amb la finalitat d'identificar nous biomarcadors per a l'avaluació del funcionament de l'autoregulació cerebral i la vasorreactivitat cerebral, i globalment, del bon funcionament cerebral. Aquests estudis s'han centrat en la investigació de la fisiologia cerebral microvascular en resposta a un estímul no invasiu, sense la necessitat de la col·laboració dels pacients, ni tampoc de cap material addicional; aquest estímul és un simple canvi de posició de la capçalera del llit. Curiosament, el dit canvi de posició de la capçalera del llit, juntament amb la mesura del flux sanguini cerebral de la microvasculatura, han demostrat ser un protocol amb potencial per aportar informació sobre l'estat de l'autoregulació cerebral. A més a més, a través d'aquest protocol s'han pogut estudiar l'estat del benestar cerebral al llarg del temps, els canvis deguts possiblement al tractament, així com les correlacions amb el pronòstic d'aquests pacients. En resum, aquesta tesi amplia els límits de l'òptica difusa, obrint camí a noves aplicacions clíniques en els hospitalsPostprint (published version