publications

2024

1. data analysis

   The fNIRS Reproducibility Study Hub (FRESH): Exploring Variability and Enhancing Transparency in fNIRS Neuroimaging Research

   Meryem Ayşe Yücel, Robert Luke, Rickson Coelho Mesquita, and 106 more authors

   MetaArxiv, 2024

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   In neuroimaging research, efforts to enhance replication and reproducibility have increased the focus on improving transparency, particularly in the complex data analysis processes. We conducted a multi-lab collaborative study involving 38 international teams that analyzed two functional Near-Infrared Spectroscopy (fNIRS) datasets. These teams tested seven group-level and forty individual-level hypotheses, and they submitted detailed reports on their analysis pipelines and testing outcomes. The results showed significant variability in hypothesis testing outcomes due to differences in analytical approaches. There was greater consensus in group-level analyses compared to individual-level analyses. Factors such as the pruning method, hemodynamic response function model and estimation, and statistical analysis space partly account for the variability in hypothesis testing outcomes. Additionally, we have found higher similarity in hypothesis testing outcomes across the researchers who reported higher confidence in their analysis skills. This study underscores the importance of complying with best practices in fNIRS analysis methodologies and the need for standardized analysis protocols to improve reliability and credibility.

2. critical care

   Functional near-infrared spectroscopy: A novel tool for detecting consciousness after acute severe brain injury

   Karnig Kazazian, Androu Abdalmalak, Sergio L Novi, and 7 more authors

   Proceedings of the National Academy of Sciences, 2024

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   Recent advancements in functional neuroimaging have demonstrated that some unresponsive patients in the intensive care unit retain a level of consciousness that is inconsistent with their behavioral diagnosis of awareness. Functional near-infrared spectroscopy (fNIRS) is a portable optical neuroimaging method that can be used to measure neural activity with good temporal and spatial resolution. However, the reliability of fNIRS for detecting the neural correlates of consciousness remains to be established. In a series of studies, we evaluated whether fNIRS can record sensory, perceptual, and command-driven neural processing in healthy participants and in behaviorally nonresponsive patients. At the individual healthy subject level, we demonstrate that fNIRS can detect commonly studied resting state networks, sensorimotor processing, speech-specific auditory processing, and volitional command-driven brain activity to a motor imagery task. We then tested fNIRS with three acutely brain injured patients and found that one could willfully modulate their brain activity when instructed to imagine playing a game of tennis—providing evidence of preserved consciousness despite no observable behavioral signs of awareness. The successful application of fNIRS for detecting preserved awareness among behaviorally nonresponsive patients highlights its potential as a valuable tool for uncovering hidden cognitive states in critical care settings.

2023

1. connectivity

   Improved short-channel regression for mapping resting-state functional connectivity networks using functional near-infrared spectroscopy

   S. L. Novi, A. Abdalmalak, K. Kazazian, and 4 more authors

   bioRxiv, Jun 2023

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   Resting-state functional connectivity (rsFC) is an attractive biomarker of brain function that can vary with brain injury. The simplicity of resting-state protocols coupled with the main features of functional near-infrared spectroscopy (fNIRS), such as portability and versatility, can facilitate the monitoring of unresponsive patients in acute settings at the bedside. However, accurately mapping rsFC networks is challenging due to signal contamination from non-neural components, such as scalp hemodynamics and systemic physiology. Physiological noise may be mitigated through the use of short channels which may be able to provide sufficient information to eliminate the need for additional measurement devices, decreasing the complexity of the experimental setup. To this end, we examined the extent to which systemic physiology is embedded in the short-channel data and improved short-channel regression to account for temporal heterogeneity in the scalp hemodynamics. Our findings indicate that using temporal shifts in the short-channel data increases the agreement, by 70% on average, between short-channel regression and regression that includes short channels and physiological recordings. Overall, this method decreases the need for additional physiological recordings when mapping rsFC networks, providing a viable alternative when such measurements are not available or feasible.

2. editorial

   Special Section Guest Editorial: Thirty Years of Functional Near-Infrared Spectroscopy

   David Highton, David Boas, Yasuyo Minagawa, and 2 more authors

   Neurophotonics, Jul 2023

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   Functional Near-Infrared Spectroscopy (fNIRS) is a non-invasive optical technique that measures cerebral hemodynamics across multiple regions of interest, and thereby characterises brain functional activation. Since its first description in 1993, fNIRS has undergone substantial developments in hardware, analysis techniques, and applications. Thirty years later, this technique is significantly enchancing our understanding in diverse areas of neuroscience research such as neurodevelopment, cognitive neuroscience, psychiatric disorders, neurodegenerative conditions, and brain injury management in intensive care settings. This special issue outlines the latest progress in instrumentation and analysis techniques and showcases some applications within the expanding field of fNIRS over the past decade.

3. development

   Can tactile reactivity in preterm born infants be explained by an immature cortical response to tactile stimulation in the first year? A pilot study

   Ana Carolina C. P. Machado, Livia C. Magalhães, Suelen R. Oliveira, and 4 more authors

   J. Perinatol., Jun 2023

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   This study aimed to compare preterm (PT) and full-term (FT) infants’ adaptive behavior and functional cortical response to tactile stimulus, as measured by Test of Sensory Functions in Infants and functional Near-Infrared Spectroscopy (fNIRS). Outcome measures were taken at 6 (PT = 26/FT = 21 infants) and 12 months (PT = 15/FT = 14 infants). At 6 months, poorer tactile reactivity was observed in PT, but not confirmed at 12 months. At 6 months, cortical response to tactile stimulus was found in the primary sensorimotor cortex and differences between groups did not reach significance. At 12 months, cortical response was found in the primary sensorimotor cortex and premotor area and in the somatosensory associative area, with significant less frequent response in premotor area in PT. The findings reinforce fNIRS as a tool to complement the knowledge of tactile adaptive behaviors in PT in early life.

4. dcs

   Optimizing a two-layer method for hybrid diffuse correlation spectroscopy and frequency-domain diffuse optical spectroscopy cerebral measurements in adults

   Rodrigo M. Forti, Giovani G. Martins, Wesley B. Baker, and 1 more author

   Neurophotonics, May 2023

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   Significance: The sensitivity to extracerebral tissues is a well-known confounder of diffuse optics. Two-layer (2L) head models can separate cerebral signals from extracerebral artifacts, but they also carry the risk of crosstalk between fitting parameters. Aim: We aim to implement a constrained 2L head model for hybrid diffuse correlation spectroscopy (DCS) and frequency-domain diffuse optical spectroscopy (FD-DOS) data and to characterize errors in cerebral blood flow and tissue absorption with the proposed model. Approach: The algorithm uses the analytical solution of a 2L cylinder and an a priori extracerebral layer thickness to fit multidistance FD-DOS (0.8 to 4 cm) and DCS (0.8 and 2.5 cm) data, assuming homogeneous tissue reduced scattering. We characterized the algorithm’s accuracy for simulated data with noise generated using a 2L slab and realistic adult head geometries and for in vitro phantom data. Results: Our algorithm recovered the cerebral flow index with 6.3 [2.8, 13.2]% and 34 [30, 42]% (median absolute percent error [interquartile range]) for slab and head geometries, respectively. Corresponding errors in the cerebral absorption coefficient were 5.0 [3.0, 7.9]% and 4.6 [2.4, 7.2]% for the slab and head geometries and 8 [5, 12]% for our phantom experiment. Our results were minimally sensitive to second-layer scattering changes and were robust to cross-talk between fitting parameters. Conclusions: In adults, the constrained 2L algorithm promises to improve FD-DOS/DCS accuracy compared with the conventional semi-infinite approach.

5. connectivity

   Revealing the spatiotemporal requirements for accurate subject identification with resting-state functional connectivity: a simultaneous fNIRS-fMRI study

   Sergio L. Novi, Alex C. Carvalho, Rodrigo M. Forti, and 3 more authors

   Neurophotonics, Feb 2023

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   Brain fingerprinting refers to identifying participants based on their functional patterns. Despite its success with functional magnetic resonance imaging (fMRI), brain fingerprinting with functional near-infrared spectroscopy (fNIRS) still lacks adequate validation. We investigated how fNIRS-specific acquisition features (limited spatial information and nonneural contributions) influence resting-state functional connectivity (rsFC) patterns at the intra-subject level and, therefore, brain fingerprinting. We performed multiple simultaneous fNIRS and fMRI measurements in 29 healthy participants at rest. Data were preprocessed following the best practices, including the removal of motion artifacts and global physiology. The rsFC maps were extracted with the Pearson correlation coefficient. Brain fingerprinting was tested with pairwise metrics and a simple linear classifier. Our results show that average classification accuracy with fNIRS ranges from 75% to 98%, depending on the number of runs and brain regions used for classification. Under the right conditions, brain fingerprinting with fNIRS is close to the 99.9% accuracy found with fMRI. Overall, the classification accuracy is more impacted by the number of runs and the spatial coverage than the choice of the classification algorithm. This work provides evidence that brain fingerprinting with fNIRS is robust and reliable for extracting unique individual features at the intra-subject level once relevant spatiotemporal constraints are correctly employed.

2022

1. connectivity

   Effects of Systemic Physiology on Mapping Resting-State Networks Using Functional Near-Infrared Spectroscopy

   Androu Abdalmalak, Sergio L. Novi, Karnig Kazazian, and 7 more authors

   Frontiers in Neuroscience, Mar 2022

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   Resting-state functional connectivity (rsFC) has gained popularity mainly due to its simplicity and potential for providing insights into various brain disorders. In this vein, functional near-infrared spectroscopy (fNIRS) is an attractive choice due to its portability, flexibility, and low cost, allowing for bedside imaging of brain function. While promising, fNIRS suffers from non-neural signal contaminations (i.e., systemic physiological noise), which can increase correlation across fNIRS channels, leading to spurious rsFC networks. In the present work, we hypothesized that additional measurements with short channels, heart rate, mean arterial pressure, and end-tidal CO2 could provide a better understanding of the effects of systemic physiology on fNIRS-based resting-state networks. To test our hypothesis, we acquired 12 min of resting-state data from 10 healthy participants. Unlike previous studies, we investigated the efficacy of different pre-processing approaches in extracting resting-state networks. Our results are in agreement with previous studies and reinforce the fact that systemic physiology can overestimate rsFC. We expanded on previous work by showing that removal of systemic physiology decreases intra- and inter-subject variability, increasing the ability to detect neural changes in rsFC across groups and over longitudinal studies. Our results show that by removing systemic physiology, fNIRS can reproduce resting-state networks often reported with functional magnetic resonance imaging (fMRI). Finally, the present work details the effects of systemic physiology and outlines how to remove (or at least ameliorate) their contributions to fNIRS signals acquired at rest.

2. stroke

   Modeling functional network topology following stroke through graph theory: functional reorganization and motor recovery prediction

   S.R.M. Almeida, C.A. Stefano, J. Vicentini, and 4 more authors

   Brazilian Journal of Medical and Biological Research, Aug 2022

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   The study of functional reorganization following stroke has been steadily growing supported by advances in neuroimaging techniques, such as functional magnetic resonance imaging (fMRI). Concomitantly, graph theory has been increasingly employed in neuroscience to model the brain’s functional connectivity (FC) and to investigate it in a variety of contexts. The aims of this study were: 1) to investigate the reorganization of network topology in the ipsilesional (IL) and contralesional (CL) hemispheres of stroke patients with (motor stroke group) and without (control stroke group) motor impairment, and 2) to predict motor recovery through the relationship between local topological variations of the functional network and increased motor function. We modeled the brain’s FC as a graph using fMRI data, and we characterized its interactions with the following graph metrics: degree, clustering coefficient, characteristic path length, and betweenness centrality (BC). For both patient groups, BC yielded the largest variations between the two analyzed time points, especially in the motor stroke group. This group presented significant correlations (P<0.05) between average BC changes and the improvements in upper-extremity Fugl-Meyer (UE-FM) scores at the primary sensorimotor cortex and the supplementary motor area for the CL hemisphere. These regions participate in processes related to the selection, planning, and execution of movement. Generally, higher increases in average BC over these areas were related to larger improvements in UE-FM assessment. Although the sample was small, these results suggest the possibility of using BC as an indication of brain plasticity mechanisms following stroke.

3. cognition

   Differences in brain activity between fast and slow responses on psychomotor vigilance task: an fNIRS study

   Mateus G. Nogueira, Mateus Silvestrin, Cândida S. F. Barreto, and 4 more authors

   Brain Imaging and Behavior, Jan 2022

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   Attention is a basic human function underlying every other cognitive process. It is demonstrated in the functional Magnetic Resonance Imaging literature that frontoparietal networks are involved with attentive performance while default mode networks are involved with inattentive performance. Yet, it is still not clear whether similar results would be found with functional Near-Infrared Spectroscopy. The goal of our study was to investigate differences in hemodynamic activity measured by functional Near-Infrared Spectroscopy between fast and slow responses on a simple sustained attention task both before and after stimulus onset. Thirty healthy adults took part in the study. Our results have shown differences between fast and slow responses only on channels over medial frontal cortex and inferior parietal cortex (p < 0,05). These differences were observed both before and after stimulus presentation. It is discussed that functional Near-Infrared Spectroscopy is a good tool to investigate the frontoparietal network and its relationship with performance in attention tasks; it could be used to further investigate other approaches on attention, such as the dual network model of cognitive control and brain states views based on complex systems analysis; and finally, it could be used to investigate attention in naturalistic settings.

4. review

   Neurophotonic tools for microscopic measurements and manipulation: status report

   Ahmed S. Abdelfattah, Sapna Ahuja, Taner Akkin, and 68 more authors

   Neurophotonics, Apr 2022

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   Neurophotonics was launched in 2014 coinciding with the launch of the BRAIN Initiative focused on development of technologies for advancement of neuroscience. For the last seven years, Neurophotonics’ agenda has been well aligned with this focus on neurotechnologies featuring new optical methods and tools applicable to brain studies. While the BRAIN Initiative 2.0 is pivoting towards applications of these novel tools in the quest to understand the brain, this status report reviews an extensive and diverse toolkit of novel methods to explore brain function that have emerged from the BRAIN Initiative and related large-scale efforts for measurement and manipulation of brain structure and function. Here, we focus on neurophotonic tools mostly applicable to animal studies. A companion report, scheduled to appear later this year, will cover diffuse optical imaging methods applicable to noninvasive human studies. For each domain, we outline the current state-of-the-art of the respective technologies, identify the areas where innovation is needed, and provide an outlook for the future directions.

5. atherosclerosis

   Quantification of the Tissue Oxygenation Delay Induced by Breath-Holding in Patients with Carotid Atherosclerosis

   Andrés Quiroga, Sergio Novi, Giovani Martins, and 6 more authors

   Metabolites, Nov 2022

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   Carotid artery stenosis (CAS) is a common vascular disease with long-term consequences for the brain. Although CAS is strongly associated with impaired cerebral hemodynamics and neurodegeneration, the mechanisms underlying hemodynamic impairment in the microvasculature remain unknown. In this work, we employed functional near-infrared spectroscopy (fNIRS) to introduce a methodological approach for quantifying the temporal delay of the evoked hemodynamic response. The method was validated during a vasodilatory task (breath-holding) in 50 CAS patients and 20 controls. Our results suggest that the hemodynamic response to breath-holding can be delayed by up to 6 s in the most severe patients, a significant increase from the median 4 s measured for the control group (p = 0.01). In addition, the fraction of brain regions that responded to the task decreased as the CAS severity increased, from a median of 90% in controls to 73% in the most severe CAS group (p = 0.04). The presence of collateral circulation increases the response to breath-holding and decreases the average time delays across the brain, although the number of communicating arteries alone cannot predict these fNIRS-based hemodynamic variables (p > 0.09). Overall, this work proposes a method to quantitatively assess impaired cerebral hemodynamics in CAS patients.

6. review

   Optical imaging and spectroscopy for the study of the human brain: status report

   Hasan Ayaz, Wesley B. Baker, Giles Blaney, and 57 more authors

   Neurophotonics, Aug 2022

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   This report is the second part of a comprehensive two-part series aimed at reviewing an extensive and diverse toolkit of novel methods to explore brain health and function. While the first report focused on neurophotonic tools mostly applicable to animal studies, here, we highlight optical spectroscopy and imaging methods relevant to noninvasive human brain studies. We outline current state-of-the-art technologies and software advances, explore the most recent impact of these technologies on neuroscience and clinical applications, identify the areas where innovation is needed, and provide an outlook for the future directions.

2021

1. development

   Potencialidades da espectroscopia funcional por infravermelho próximo (fNIRS) para o estudo do cérebro em desenvolvimento na primeira infância

   Vera Mateus, Júlia Scarano de Mendonça, Helga Oliveira Miguel, and 4 more authors

   In Tecnologias Aplicadas em Educação e Saúde, Aug 2021

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2. editorial

   Upcoming Neurophotonics Status Report

   Anna Devor, Darcy S Peterka, Erin M Buckley, and 1 more author

   Neurophotonics, Dec 2021

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   Forthcoming status report articles provide updates on microscopy and on diffuse optical imaging in neurophotonics.

3. development

   Hearing brain evaluated using near-infrared spectroscopy in congenital toxoplasmosis

   Ana Lívia Libardi Bertachini, Gabriela Cintra Januario, Sergio Luiz Novi, and 5 more authors

   Scientific Reports, May 2021

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   Congenital toxoplasmosis (CT) is a known cause of hearing loss directly caused by Toxoplasma gondii. Hearing loss might result from sensory, neural, or sensorineural lesions. Early treated infants rarely develop hearing loss, but retinochoroidal lesions, intracranial calcifications and hydrocephalus are common. In this study, we aimed to evaluate the brain evoked hemodynamic responses of CT and healthy infants during four auditory stimuli: mother infant directed speech, researcher infant directed speech, mother reading and researcher recorded. Children underwent Transitionally Evoked Otoacoustic Emission Auditory Testing and Automated Brainstem Auditory Response tests with normal auditory results, but with a tendency for greater latencies in the CT group compared to the control group. We assessed brain hemodynamics with functional near-infrared spectroscopy (fNIRS) measurements from 61 infants, and we present fNIRS results as frequency maps of activation and deactivation for each stimulus. By evaluating infants in the three first months of life, we observed an individual heterogeneous brain activation pattern in response to all auditory stimuli for both groups. Each channel was activated or deactivated in less than 30% of children for all stimuli. There is a need of prospective studies to evaluate if the neurologic or auditory changes course with compromise of children outcomes.

4. covid-19

   Peripheral microcirculatory alterations are associated with the severity of acute respiratory distress syndrome in COVID-19 patients admitted to intermediate respiratory and intensive care units.

   Jaume Mesquida, A. Caballer, L. Cortese, and 65 more authors

   Critical care, Nov 2021

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   COVID-19 is primarily a respiratory disease; however, there is also evidence that it causes endothelial damage in the microvasculature of several organs. The aim of the present study is to characterize in vivo the microvascular reactivity in peripheral skeletal muscle of severe COVID-19 patients.

5. neurovascular

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

   Clara Gregori-Pla, Rickson C. Mesquita, Christopher G. Favilla, and 22 more authors

   BMC Neurology, Apr 2021

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   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. 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. 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). 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.

6. computer vision

   Accurate Image-guided (Re)Placement of NIRS Probes

   Shin-Ting Wu, Jose Angel Ivan Rubianes Silva, Sérgio Luiz Novi, and 3 more authors

   Computer Methods and Programs in Biomedicine, Mar 2021

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   BACKGROUND AND OBJECTIVE: Functional near-infrared spectroscopy (fNIRS) has become an attractive choice to neuroscience because of its high temporal resolution, ease of use, non-invasiveness, and affordability. With the advent of wearable fNIRS technology, on-the-spot studies of brain function have become viable. However, the lack of within-subject reproducibility is one of the barriers to the full acceptability of fNIRS. To support the validation of the claim that within-subject reproducibility of fNIRS could benefit from accurate anatomical information, we present in this paper a method to develop an image-based system that improves the placement of the sensors on the scalp at interactive rates. METHODS: The proposed solution consists of an electromagnetic digitizer and an interactive visualization system that allows monitoring the movements of the digitizer on a real head with respect to the underlying cerebral cortical structures. GPU-based volume raycasting rendering is applied to unveil these structures from the corresponding magnetic resonance imaging volume. Scalp and cortical surface are estimated from the scanned volume to improve depth perception. An alignment algorithm between the real and scanned heads is devised to visually feedback the position of the stylus of the digitizer. Off-screen rendering of the depthmaps of the visible surfaces makes spatial positioning of a 2D interaction pointer possible. RESULTS: We evaluated the alignment accuracy using four to eight anatomical landmarks and found seven to be a good compromise between precision and efficiency. Next, we evaluated reproducibility in positioning five arbitrarily chosen points on three volunteers by four operators over five sessions. In every session, seven anatomical landmarks were applied in the alignment of the real and the scanned head. For the same volunteer, one-way analysis of variance (ANOVA) revealed no significant differences within the five points digitized by the same operator over five sessions (α = 0.05). In addition, preliminary study of motor cortex activation by right-hand finger tapping showed the potential of our approach to increase functional fNIRS reproducibility. CONCLUSIONS: Results of experiments suggest that the enhancement of the visualization of the location of the probes on the scalp, relative to the underlying cortical structures, improves reproducibility of fNIRS measurements. As further work, we plan to study the fNIRS reproducibility in other cortical regions and in clinical settings using the proposed system.

2020

1. data analysis

   Integration of Spatial Information Increases Reproducibility in Functional Near-Infrared Spectroscopy.

   Sérgio Luiz Novi, Edwin Johan Forero, Jose Angel Ivan Rubianes Silva, and 5 more authors

   Frontiers in Neuroscience, Mar 2020

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   As functional near-infrared spectroscopy (fNIRS) is developed as a neuroimaging technique and becomes an option to study a variety of populations and tasks, the reproducibility of the fNIRS signal is still subject of debate. By performing test-retest protocols over different functional tasks, several studies agree that the fNIRS signal is reproducible over group analysis, but the inter-subject and within-subject reproducibility is poor. The high variability at the first statistical level is often attributed to global systemic physiology. In the present work, we revisited the reproducibility of the fNIRS signal during a finger-tapping task across multiple sessions on the same and different days. We expanded on previous studies by hypothesizing that the lack of spatial information of the optodes contributes to the low reproducibility in fNIRS, and we incorporated a real-time neuronavigation protocol to provide accurate cortical localization of the optodes. Our proposed approach was validated in 10 healthy volunteers, and our results suggest that the addition of neuronavigation can increase the within-subject reproducibility of the fNIRS data, particularly in the region of interest. Unlike traditional approaches to positioning the optodes, in which low intra-subject reproducibility has been found, we were able to obtain consistent and robust activation of the contralateral primary motor cortex at the intra-subject level using a neuronavigation protocol. Overall, our findings support the hypothesis that at least part of the variability in fNIRS cannot be only attributed to global systemic physiology. The use of neuronavigation to guide probe positioning, as proposed in this work, has impacts to longitudinal protocols performed with fNIRS.

2. data analysis

   Functional near-infrared spectroscopy for speech protocols: characterization of motion artifacts and guidelines for improving data analysis

   Sergio L Novi, Erin Roberts, Danielle Spagnuolo, and 8 more authors

   Neurophotonics, Jan 2020

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   Monitoring speech tasks with functional near-infrared spectroscopy (fNIRS) enables investigation of speech production mechanisms and informs treatment strategies for speech-related disorders such as stuttering. Unfortunately, due to movement of the temporalis muscle, speech production can induce relative movement between probe optodes and skin. These movements generate motion artifacts during speech tasks. In practice, spurious hemodynamic responses in functional activation signals arise from lack of information about the consequences of speech-related motion artifacts, as well as from lack of standardized processing procedures for fNIRS signals during speech tasks. To this end, we characterize the effects of speech production on fNIRS signals, and we introduce a systematic analysis to ameliorate motion artifacts. The study measured 50 healthy subjects performing jaw movement (JM) tasks and found that JM produces two different patterns of motion artifacts in fNIRS. To remove these unwanted contributions, we validate a hybrid motion-correction algorithm based sequentially on spline interpolation and then wavelet filtering. We compared performance of the hybrid algorithm with standard algorithms based on spline interpolation only and wavelet decomposition only. The hybrid algorithm corrected 94% of the artifacts produced by JM, and it did not lead to spurious responses in the data. We also validated the hybrid algorithm during a reading task performed under two different conditions: reading aloud and reading silently. For both conditions, we observed significant cortical activation in brain regions related to reading. Moreover, when comparing the two conditions, good agreement of spatial and temporal activation patterns was found only when data were analyzed using the hybrid approach. Overall, the study demonstrates a standardized processing scheme for fNIRS data during speech protocols. The scheme decreases spurious responses and intersubject variability due to motion artifacts.

3. instrumentation

   Real-Time Monitoring of Neurocritical Patients with Diffuse Optical Spectroscopies

   Rodrigo Menezes Forti, Marilise Katsurayama, Lenise Valler, and 6 more authors

   Journal of Visualized Experiments, Nov 2020

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   Neurophysiological monitoring is an important goal in the treatment of neurocritical patients, as it may prevent secondary damage and directly impact morbidity and mortality rates. However, there is currently a lack of suitable non-invasive, real-time technologies for continuous monitoring of cerebral physiology at the bedside. Diffuse optical techniques have been proposed as a potential tool for bedside measurements of cerebral blood flow and cerebral oxygenation in case of neurocritical patients. Diffuse optical spectroscopies have been previously explored to monitor patients in several clinical scenarios ranging from neonatal monitoring to cerebrovascular interventions in adults. However, the feasibility of the technique to aid clinicians by providing real-time information at the bedside remains largely unaddressed. Here, we report the translation of a diffuse optical system for continuous real-time monitoring of cerebral blood flow, cerebral oxygenation, and cerebral oxygen metabolism during intensive care. The real-time feature of the instrument could enable treatment strategies based on patient-specific cerebral physiology rather than relying on surrogate metrics, such as arterial blood pressure. By providing real-time information on the cerebral circulation at different time scales with relatively cheap and portable instrumentation, this approach may be especially useful in low-budget hospitals, in remote areas and for monitoring in open fields (e.g., defense and sports).

4. atherosclerosis

   Avaliação da resposta hemodinâmica cerebral através da monitorização com a espectroscopia próxima ao infravermelho (NIRS) em pacientes com doença aterosclerótica da artéria carótida submetidos a endarterectomia

   Letícia Cristina Dalledone Siqueira Rein, Daniel Emílio Dalledone Siqueira, Ana Terezinha Guillaumon, and 3 more authors

   Jornal Vascular Brasileiro, Nov 2020

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   Contexto A espectroscopia próxima ao infravermelho (NIRS) é uma técnica não invasiva que detecta as alterações hemodinâmicas teciduais. A NIRS pode monitorar de forma contínua as informações fisiológicas vasculares intracranianas. Por ser portátil, ela pode ser utilizada à beira do leito e no centro cirúrgico.

5. critical care

   Real-Time Non-invasive Assessment of Cerebral Hemodynamics With Diffuse Optical Spectroscopies in a Neuro Intensive Care Unit: An Observational Case Study.

   Rodrigo M Forti, Marilise Katsurayama, Julien Menko, and 5 more authors

   Frontiers in Medicine, Nov 2020

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   Prevention of secondary damage is an important goal in the treatment of severe neurological conditions, such as major head trauma or stroke. However, there is currently a lack of non-invasive methods for monitoring cerebral physiology. Diffuse optical methods have been proposed as an inexpensive, non-invasive bedside monitor capable of providing neurophysiology information in neurocritical patients. However, the reliability of the technique to provide accurate longitudinal measurement during the clinical evolution of a patient remains largely unaddressed. Here, we report on the translation of a hybrid diffuse optical system combining frequency domain diffuse optical spectroscopy (FD-DOS) and diffuse correlation spectroscopy (DCS) for real-time monitoring of cerebral physiology in a neuro intensive care unit (neuro-ICU). More specifically, we present a case study of a patient admitted with a high-grade aneurysmal subarachnoid hemorrhage, who was monitored throughout hospitalization. We show that the neurophysiological parameters measured by diffuse optics at the bedside are consistent with the clinical evolution of the patient at all the different stages following its brain lesion. These data provide support for clinical translation of DOS/DCS as a useful biomarker of neurophysiology in the neuro-ICU, particularly in locations where other clinical resources are limited.

2019

1. stroke

   Perfusion Enhancement with Respiratory Impedance After Stroke (PERI-Stroke).

   Christopher G Favilla, Rodrigo M Forti, Ahmad Zamzam, and 9 more authors

   Neurotherapeutics, Nov 2019

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   Intrathoracic pressure influences cardiac output and may affect cerebral blood flow (CBF). We aimed to quantify the cerebral hemodynamic response to intrathoracic pressure reduction in patients with acute ischemic stroke using a noninvasive respiratory impedance (RI) device. We assessed low-level (6 cm H2O) and high-level (12 cm H2O) RI in 17 spontaneously breathing patients within 72 h of anterior circulation acute ischemic stroke. Average age was 65 years, and 35% were female. Frontal lobe tissue perfusion and middle cerebral artery velocity (MCAv) were continuously monitored with optical diffuse correlation spectroscopy (DCS) and transcranial Doppler ultrasound, respectively. High-level RI resulted in a 7% increase in MCAv (p = 0.004). MCAv varied across all studied levels (baseline vs low-level vs high-level, p = 0.006), with a significant test of trend (p = 0.002). Changes were not seen in DCS measured tissue perfusion by nonparametric pairwise comparison. Mixed effects regression analysis identified a small increase in both MCAv (low-level RI: β 2.1, p < 0.001; high-level RI: β 5.0, p < 0.001) and tissue-level flow (low-level RI: β 5.4, p < 0.001; high-level RI: β 5.9, p < 0.001). There was a small increase in mean arterial pressure during low-level and high-level RI, 4% (p = 0.013) and 4% (p = 0.017), respectively. End-tidal CO2 remained stable throughout the protocol. RI was well tolerated. Manipulating intrathoracic pressure via noninvasive RI was safe and produced a small but measurable increase in cerebral perfusion in acute ischemic stroke patients. Future studies are warranted to assess whether RI is feasible and tolerable for prolonged use in hyperacute stroke management.

2. stroke

   Cerebral Blood Flow Response During Bolus Normal Saline Infusion After Ischemic Stroke.

   Michael T Mullen, Ashwin B Parthasarathy, Ali Zandieh, and 10 more authors

   Journal of Stroke and Cerebrovascular Diseases, Nov 2019

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   GOALS: We quantified cerebral blood flow response to a 500 cc bolus of 0.9%% normal saline (NS) within 96 hours of acute ischemic stroke (AIS) using diffuse correlation spectroscopy (DCS). MATERIALS AND METHODS: Subjects with AIS in the anterior, middle, or posterior cerebral artery territory were enrolled within 96 hours of symptom onset. DCS measured relative cerebral blood flow (rCBF) in the bilateral frontal lobes for 15 minutes at rest (baseline), during a 30-minute infusion of 500 cc NS (bolus), and for 15 minutes after completion (post-bolus). Mean rCBF for each time period was calculated for individual subjects and median rCBF for the population was compared between time periods. Linear regression was used to evaluate for associations between rCBF and clinical features. RESULTS: Among 57 subjects, median rCBF (IQR) increased relative to baseline in the ipsilesional hemisphere by 17% (-2.0%, 43.1%), P< 0.001, and in the contralesional hemisphere by 13.3% (-4.3%, 36.0%), P < .004. No significant associations were found between ipsilesional changes in rCBF and age, race, infarct size, infarct location, presence of large vessel stenosis, NIH stroke scale, or symptom duration. CONCLUSION: A 500 cc bolus of .9% NS produced a measurable increase in rCBF in both the affected and nonaffected hemispheres. Clinical features did not predict rCBF response.

3. stroke

   Transcranial Optical Monitoring of Cerebral Hemodynamics in Acute Stroke Patients during Mechanical Thrombectomy.

   Rodrigo M Forti, Christopher G Favilla, Jeffrey M Cochran, and 14 more authors

   Journal of Stroke and Cerebrovascular Diseases, Nov 2019

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   INTRODUCTION: Mechanical thrombectomy is revolutionizing treatment of acute stroke due to large vessel occlusion (LVO). Unfortunately, use of the modified Thrombolysis in Cerebral Infarction score (mTICI) to characterize recanalization of the cerebral vasculature does not address microvascular perfusion of the distal parenchyma, nor provide more than a vascular "snapshot." Thus, little is known about tissue-level hemodynamic consequences of LVO recanalization. Diffuse correlation spectroscopy (DCS) and diffuse optical spectroscopy (DOS) are promising methods for continuous, noninvasive, contrast-free transcranial monitoring of cerebral microvasculature. METHODS: Here, we use a combined DCS/DOS system to monitor frontal lobe hemodynamic changes during endovascular treatment of 2 patients with ischemic stroke due to internal carotid artery (ICA) occlusions. RESULTS AND DISCUSSION: The monitoring instrument identified a recanalization-induced increase in ipsilateral cerebral blood flow (CBF) with little or no concurrent change in contralateral CBF and extracerebral blood flow. The results suggest that diffuse optical monitoring is sensitive to intracerebral hemodynamics in patients with ICA occlusion and can measure microvascular responses to mechanical thrombectomy.

4. connectivity

   Identifying individuals using fNIRS-based cortical connectomes.

   Júlia de Souza Rodrigues, Fernanda Lenita Ribeiro, João Ricardo Sato, and 2 more authors

   Biomedical Optics Express, Jun 2019

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   The fMRI-based functional connectome was shown to be sufficiently unique to allow individual identification (fingerprinting). We aimed to test whether a fNIRS-based connectome could also be used to identify individuals. Forty-four participants performed experimental protocols that consisted of two periods of resting-state interleaved by a cognitive task period. Connectome identification was performed for all possible pairwise combinations of the three periods. The influence of hemodynamic global variation was tested using global signal regression and principal component analysis. High identification accuracies well-above chance level (2.3%) were observed overall, being particularly high (93%) to the oxyhemoglobin signal between resting conditions. Our results suggest that fNIRS is a suitable technique to assess connectome fingerprints.

5. development

   Changes of functional response in sensorimotor cortex of preterm and full-term infants during the first year_ An fNIRS study

   Suelen Rosa de Oliveira, Ana Carolina C P Machado, Jonas Jardim de Paula, and 4 more authors

   Early Human Development, Apr 2019

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   Early Human Development, 133 (2019) 23-28. doi:10.1016/j.earlhumdev.2019.04.007

2018

1. dcs

   Noninvasive continuous optical monitoring of absolute cerebral blood flow in critically ill adults.

   Lian He, Wesley B Baker, Daniel Milej, and 12 more authors

   Neurophotonics, Apr 2018

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   We investigate a scheme for noninvasive continuous monitoring of absolute cerebral blood flow (CBF) in adult human patients based on a combination of time-resolved dynamic contrast-enhanced near-infrared spectroscopy (DCE-NIRS) and diffuse correlation spectroscopy (DCS) with semi-infinite head model of photon propogation. Continuous CBF is obtained via calibration of the DCS blood flow index (BFI) with absolute CBF obtained by intermittent intravenous injections of the optical contrast agent indocyanine green. A calibration coefficient ( γ ) for the CBF is thus determined, permitting conversion of DCS BFI to absolute blood flow units at all other times. A study of patients with acute brain injury ( N=7 ) is carried out to ascertain the stability of γ . The patient-averaged DCS calibration coefficient across multiple monitoring days and multiple patients was determined, and good agreement between the two calibration coefficients measured at different times during single monitoring days was found. The patient-averaged calibration coefficient of 1.24×109  (mL/100  g/min)/(cm2/s) was applied to previously measured DCS BFI from similar brain-injured patients; in this case, absolute CBF was underestimated compared with XeCT, an effect we show is primarily due to use of semi-infinite homogeneous models of the head.

2. development

   Association between hemodynamic activity and motor performance in six-month-old full-term and preterm infants: a functional near-infrared spectroscopy study

   Suelen Rosa de Oliveira, Ana Carolina Cabral de Paula Machado, Jonas Jardim de Paula, and 7 more authors

   Neurophotonics, Oct 2018

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   This study aimed to assess task-induced activation in motor cortex and its association with motor performance in full-term and preterm born infants at six months old. A cross-sectional study of 73 six-month-old infants was conducted (35 full-term and 38 preterm infants). Motor performance was assessed using the Bayley Scales of Infant Development third edition—Bayley-III. Brain hemodynamic activity during motor task was measured by functional near-infrared spectroscopy (fNIRS). Motor performance was similar in full-term and preterm infants. However, differences in hemodynamic response were identified. Full terms showed a more homogeneous unilateral and contralateral activated area, whereas in preterm-born the activation response was predominantly bilateral. The full-term group also exhibited a shorter latency for the hemodynamic response than the preterm group. Hemodynamic activity in the left sensorimotor region was positively associated with motor performance measured by Bayley-III. The results highlight the adequacy of fNIRS to assess differences in task-induced activation in sensorimotor cortex between groups. The association between motor performance and the hemodynamic activity require further investigation and suggest that fNIRS can become a suitable auxiliary tool to investigate aspects of neural basis on early development of motor abilities.

2017

1. connectivity

   Development of Novel Methods to Investigate the Brain at Rest

   Sergio Luiz Novi Junior, Wagner Alan Aparecido da Rocha, Alex de Castro Carvalho, and 6 more authors

   Revista Brasileira de Física Médica, Nov 2017

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   O funcionamento cerebral parece ser altamente organizado mesmo na ausência de tarefas específicas. Neste trabalho usamos teoria de grafos num experimento de neuroimagem multimodal com ressonância magnética funcional e espectroscopia no infravermelho próximo para entender melhor a conectividade funcional durante o estado de repouso. Nossos resultados sugerem que, independentemente das diferenças entre voluntários, suas propriedades de grafos é muito similar. Além disso, propomos uma nova abordagem para analisar a conectividade de um grupo baseado na frequência de distribuição de links.

2. atherosclerosis

   Use of near-infrared spectroscopy to probe occlusion severity in patients diagnosed with carotid atherosclerotic disease

   E J Forero, S L Novi, W M Avelar, and 7 more authors

   Medical Research Archives, Jun 2017

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   Atherosclerotic disease has been associated with increased risk of severe neurovascular consequences including transient ischemic attacks, ischemic strokes, and even mortality. Following the onset of carotid stenosis, the brain undergoes different compensatory mechanisms to provide adequate perfusion in order to maintain brain metabolism. In this study, we employed near-infrared spectroscopy (NIRS) to better ...

3. cognition

   Drug abusers have impaired cerebral oxygenation and cognition during exercise

   Kell Grandjean da Costa, Vanessa Soares Rachetti, Weslley Quirino Alves da Silva, and 8 more authors

   Plos One, Nov 2017

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   Background Individuals with Substance Use Disorder (SUD) have lower baseline metabolic activity of the prefrontal cortex (PFC) associated with impairment of cognitive functions in decision-making and inhibitory control. Aerobic exercise has shown to improve PFC function and cognitive performance, however, its effects on SUD individuals remain unclear. Purpose To verify the cognitive performance and oxygenation of the PFC during an incremental exercise in SUD individuals. Methods Fourteen individuals under SUD treatment performed a maximum graded exercise test on a cycle ergometer with continuous measurements of oxygen consumption, PFC oxygenation, and inhibitory control (Stroop test) every two minutes of exercise at different intensities. Fifteen non-SUD individuals performed the same protocol and were used as control group. Results Exercise increased oxyhemoglobin (O2Hb) and total hemoglobin (tHb) by 9% and 7%, respectively. However, when compared to a non-SUD group, this increase was lower at high intensities (p<0.001), and the inhibitory cognitive control was lower at rest and during exercise (p<0.007). In addition, PFC hemodynamics during exercise was inversely correlated with inhibitory cognitive performance (reaction time) (r = -0.62, p = 0.001), and a lower craving perception for the specific abused substance (p = 0.0189) was reported immediately after exercise. Conclusion Despite SUD individuals having their PFC cerebral oxygenation increased during exercise, they presented lower cognition and oxygenation when compared to controls, especially at elevated intensities. These results may reinforce the role of exercise as an adjuvant treatment to improve PFC function and cognitive control in individuals with SUD.

4. cognition

   Affect during incremental exercise: The role of inhibitory cognition, autonomic cardiac function, and cerebral oxygenation

   Weslley Quirino Alves da Silva, Eduardo Bodnariuc Fontes, Rodrigo Menezes Forti, and 8 more authors

   Plos One, Nov 2017

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   Background Pleasure is a key factor for physical activity behavior in sedentary individuals. Inhibitory cognitive control may play an important role in pleasure perception while exercising, especially at high intensities. In addition, separate work suggests that autonomic regulation and cerebral hemodynamics influence the affective and cognitive responses during exercise. Purpose We investigated the effects of exercise intensity on affect, inhibitory control, cardiac autonomic function, and prefrontal cortex (PFC) oxygenation. Methods Thirty-seven sedentary young adults performed two experimental conditions (exercise and control) in separate sessions in a repeated-measures design. In the exercise condition, participants performed a maximum graded exercise test on a cycle ergometer as we continuously measured oxygen consumption, heart rate variability (HRV), and PFC oxygenation. At each of 8 intensity levels we also measured inhibitory control (Stroop test), associative and dissociative thoughts (ADT), and affective/pleasure ratings. In the control condition, participants sat motionless on a cycle ergometer without active pedaling, and we collected the same measures at the same points in time as the exercise condition. We evaluated the main effects and interactions of exercise condition and intensity level for each measure using two-way repeated measures ANOVAs. Additionally, we evaluated the relationship between affect and inhibitory control, ADT, HRV, and PFC oxygenation using Pearson’s correlation coefficients. Results For exercise intensities below and at the ventilatory threshold (VT), participants reported feeling neutral, with preservation of inhibitory control, while intensities above the VT were associated with displeasure (p<0.001), decreased inhibitory control and HRV (p<0.001), and increased PFC oxygenation (p<0.001). At the highest exercise intensity, pleasure was correlated with the low-frequency index of HRV (r = -0.34; p<0.05) and the low-frequency/high-frequency HRV ratio (r = -0.33; p<0.05). PFC deoxyhemoglobin was correlated with pleasure two stages above the VT (r = -0.37; p<0.05). Conclusion Our results support the notion that exercise at high intensities influences inhibitory control and one’s perception of pleasure, which are linked to changes in cardiac autonomic control and cerebral hemodynamics. These findings strengthen the existence of an integrated brain-heart-body system and highlight the importance of exercise intensity in exercise-related behavior in sedentary individuals.

5. modelling

   Noninvasive optical monitoring of critical closing pressure and arteriole compliance in human subjects

   Wesley B Baker, Ashwin B Parthasarathy, Kimberly P Gannon, and 12 more authors

   Journal of Cerebral Blood Flow & Metabolism, Nov 2017

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   The critical closing pressure (CrCP) of the cerebral circulation depends on both tissue intracranial pressure and vasomotor tone. CrCP defines the arterial blood pressure (ABP) at which cerebral blood flow approaches zero, and their difference (ABP − CrCP) is an accurate estimate of cerebral perfusion pressure. Here we demonstrate a novel non-invasive technique for continuous monitoring of CrCP at the bedside. The methodology combines optical diffuse correlation spectroscopy (DCS) measurements of pulsatile cerebral blood flow in arterioles with concurrent ABP data during the cardiac cycle. Together, the two waveforms permit calculation of CrCP via the two-compartment Windkessel model for flow in the cerebral arterioles. Measurements of CrCP by optics (DCS) and transcranial Doppler ultrasound (TCD) were carried out in 18 healthy adults; they demonstrated good agreement (R = 0.66, slope = 1.14 ± 0.23) with means of 11.1 ± 5.0 and 13.0 ± 7.5 mmHg, respectively. Additionally, a potentially useful and rarely measured arteriole compliance parameter was derived from the phase difference between ABP and DCS arteriole blood flow waveforms. The measurements provide evidence that DCS signals originate predominantly from arteriole blood flow and are well suited for long-term continuous monitoring of CrCP and assessment of arteriole compliance in the clinic.

2016

1. complexity

   Self-Organization and Brain Function

   Jörg P Pfannmöller, Rickson C Mesquita, Luis C T Herrera, and 1 more author

   GigaScience, Nov 2016

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2. editorial

   Recent Advances in Optical Spectroscopic and Imaging Methods for Medicine and Biology

   Yu Shang, Zhiyu Qian, Rickson C. Mesquita, and 1 more author

   Journal of Spectroscopy, Nov 2016

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3. connectivity

   Resting state connectivity patterns with near-infrared spectroscopy data of the whole head.

   Sergio L Novi, Renato B M L Rodrigues, and R C Mesquita

   Biomedical Optics Express, Jul 2016

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   Resting state cerebral dynamics has been a useful approach to explore the brain’s functional organization. In this study, we employed graph theory to deeply investigate resting state functional connectivity (rs-FC) as measured by near-infrared spectroscopy (NIRS). Our results suggest that network parameters are very similar across time and subjects. We also identified the most frequent connections between brain regions and the main hubs that participate in the spontaneous activity of brain hemodynamics. Similar to previous findings, we verified that symmetrically located brain areas are highly connected. Overall, our results introduce new insights in NIRS-based functional connectivity at rest.

2015

1. spinal cord

   Fiber-optic Monitoring of Spinal Cord Hemodynamics in Experimental Aortic Occlusion

   Angela S. Kogler, Thomas V. Bilfinger, Robert M. Galler, and 5 more authors

   Anesthesiology, Dec 2015

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   Background: Spinal cord ischemia occurs frequently during thoracic aneurysm repair. Current methods based on electrophysiology techniques to detect ischemia are indirect, non-specific, and temporally slow. In this article, the authors report the testing of a spinal cord blood flow and oxygenation monitor, based on diffuse correlation and optical spectroscopies, during aortic occlusion in a sheep model. Methods: Testing was carried out in 16 Dorset sheep. Sensitivity in detecting spinal cord blood flow and oxygenation changes during aortic occlusion, pharmacologically induced hypotension and hypertension, and physiologically induced hypoxia/hypercarbia was assessed. Accuracy of the diffuse correlation spectroscopy measurements was determined via comparison with microsphere blood flow measurements. Precision was assessed through repeated measurements in response to pharmacologic interventions. Results: The fiber-optic probe can be placed percutaneously and is capable of continuously measuring spinal cord blood flow and oxygenation preoperatively, intraoperatively, and postoperatively. The device is sensitive to spinal cord blood flow and oxygenation changes associated with aortic occlusion, immediately detecting a decrease in blood flow (−65 ± 32%; n = 32) and blood oxygenation (−17 ± 13%, n = 11) in 100% of trials. Comparison of spinal cord blood flow measurements by the device with microsphere measurements led to a correlation of R2 = 0.49, P < 0.01, and the within-sheep coefficient of variation was 9.69%. Finally, diffuse correlation spectroscopy is temporally more sensitive to ischemic interventions than motor-evoked potentials. Conclusion: The first-generation spinal fiber-optic monitoring device offers a novel and potentially important step forward in the monitoring of spinal cord ischemia.

2. neurophysiology

   Cerebral hemodynamics at altitude: effects of hyperventilation and acclimatization on cerebral blood flow and oxygenation.

   Matthew R Sanborn, Mark E Edsell, Meeri N Kim, and 8 more authors

   Wilderness & Environmental Medicine, Dec 2015

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   OBJECTIVE: Alterations in cerebral blood flow (CBF) and cerebral oxygenation are implicated in altitude-associated diseases. We assessed the dynamic changes in CBF and peripheral and cerebral oxygenation engendered by ascent to altitude with partial acclimatization and hyperventilation using a combination of near-infrared spectroscopy, transcranial Doppler ultrasound, and diffuse correlation spectroscopy. METHODS: Peripheral (Spo2) and cerebral (Scto2) oxygenation, end-tidal carbon dioxide (ETCO2), and cerebral hemodynamics were studied in 12 subjects using transcranial Doppler and diffuse correlation spectroscopy (DCS) at 75 m and then 2 days and 7 days after ascending to 4559 m above sea level. After obtaining baseline measurements, subjects hyperventilated to reduce baseline ETCO2 by 50%, and a further set of measurements were obtained. RESULTS: Cerebral oxygenation and peripheral oxygenation showed a divergent response, with cerebral oxygenation decreasing at day 2 and decreasing further at day 7 at altitude, whereas peripheral oxygenation decreased on day 2 before partially rebounding on day 7. Cerebral oxygenation decreased after hyperventilation at sea level (Scto2 from 68.8% to 63.5%; P<.001), increased after hyperventilation after 2 days at altitude (Scto2 from 65.6% to 69.9%; P=.001), and did not change after hyperventilation after 7 days at altitude (Scto2 from 62.2% to 63.3%; P=.35). CONCLUSIONS: An intensification of the normal cerebral hypocapnic vasoconstrictive response occurred after partial acclimatization in the setting of divergent peripheral and cerebral oxygenation. This may help explain why hyperventilation fails to improve cerebral oxygenation after partial acclimatization as it does after initial ascent. The use of DCS is feasible at altitude and provides a direct measure of CBF indices with high temporal resolution.

3. modelling

   Pressure modulation algorithm to separate cerebral hemodynamic signals from extracerebral artifacts.

   Wesley B Baker, Ashwin B Parthasarathy, Tiffany S Ko, and 8 more authors

   Neurophotonics, Dec 2015

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   We introduce and validate a pressure measurement paradigm that reduces extracerebral contamination from superficial tissues in optical monitoring of cerebral blood flow with diffuse correlation spectroscopy (DCS). The scheme determines subject-specific contributions of extracerebral and cerebral tissues to the DCS signal by utilizing probe pressure modulation to induce variations in extracerebral blood flow. For analysis, the head is modeled as a two-layer medium and is probed with long and short source-detector separations. Then a combination of pressure modulation and a modified Beer-Lambert law for flow enables experimenters to linearly relate differential DCS signals to cerebral and extracerebral blood flow variation without a priori anatomical information. We demonstrate the algorithm’s ability to isolate cerebral blood flow during a finger-tapping task and during graded scalp ischemia in healthy adults. Finally, we adapt the pressure modulation algorithm to ameliorate extracerebral contamination in monitoring of cerebral blood oxygenation and blood volume by near-infrared spectroscopy.

4. molecular biology

   HIF modulation of Wnt signaling regulates skeletal myogenesis in vivo.

   Amar J Majmundar, David S M Lee, D S M Lee, and 12 more authors

   Development, Jul 2015

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   Deeper insight into the molecular pathways that orchestrate skeletal myogenesis should enhance our understanding of, and ability to treat, human skeletal muscle disease. It is now widely appreciated that nutrients, such as molecular oxygen (O2), modulate skeletal muscle formation. During early stages of development and regeneration, skeletal muscle progenitors reside in low O2 environments before local blood vessels and differentiated muscle form. Moreover, low O2 availability (hypoxia) impedes progenitor-dependent myogenesis in vitro through multiple mechanisms, including activation of hypoxia inducible factor 1α (HIF1α). However, whether HIF1α regulates skeletal myogenesis in vivo is not known. Here, we explored the role of HIF1α during murine skeletal muscle development and regeneration. Our results demonstrate that HIF1α is dispensable during embryonic and fetal myogenesis. However, HIF1α negatively regulates adult muscle regeneration after ischemic injury, implying that it coordinates adult myogenesis with nutrient availability in vivo. Analyses of Hif1a mutant muscle and Hif1a-depleted muscle progenitors further suggest that HIF1α represses myogenesis through inhibition of canonical Wnt signaling. Our data provide the first evidence that HIF1α regulates skeletal myogenesis in vivo and establish a novel link between HIF and Wnt signaling in this context.

2014

1. stroke

   Response to Letter Regarding Article, “Optical Bedside Monitoring of Cerebral Blood Flow in Acute Ischemic Stroke Patients During Head-of-Bed Manipulation”

   Rickson C. Mesquita, Christopher G. Favilla, Arjun G. Yodh, and 1 more author

   Stroke, Jul 2014

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2. modelling

   Modified Beer-Lambert law for blood flow

   Wesley B. Baker, Ashwin B. Parthasarathy, David R. Busch, and 3 more authors

   Biomedical Optics Express, Jul 2014

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   We develop and validate a Modified Beer-Lambert law for blood flow based on diffuse correlation spectroscopy (DCS) measurements. The new formulation enables blood flow monitoring from temporal intensity autocorrelation function data taken at single or multiple delay-times. Consequentially, the speed of the optical blood flow measurement can be substantially increased. The scheme facilitates blood flow monitoring of highly scattering tissues in geometries wherein light propagation is diffusive or non-diffusive, and it is particularly well-suited for utilization with pressure measurement paradigms that employ differential flow signals to reduce contributions of superficial tissues.

3. stroke

   Optical bedside monitoring of cerebral blood flow in acute ischemic stroke patients during head-of-bed manipulation.

   Christopher G Favilla, R C Mesquita, Michael Mullen, and 8 more authors

   Stroke, Jul 2014

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   BACKGROUND AND PURPOSE: A primary goal of acute ischemic stroke (AIS) management is to maximize perfusion in the affected region and surrounding ischemic penumbra. However, interventions to maximize perfusion, such as flat head-of-bed (HOB) positioning, are currently prescribed empirically. Bedside monitoring of cerebral blood flow (CBF) allows the effects of interventions such as flat HOB to be monitored and may ultimately be used to guide clinical management. METHODS: Cerebral perfusion was measured during HOB manipulations in 17 patients with unilateral AIS affecting large cortical territories in the anterior circulation. Simultaneous measurements of frontal CBF and arterial flow velocity were performed with diffuse correlation spectroscopy and transcranial Doppler ultrasound, respectively. Results were analyzed in the context of available clinical data and a previous study. RESULTS: Frontal CBF, averaged over the patient cohort, decreased by 17% (P=0.034) and 15% (P=0.011) in the ipsilesional and contralesional hemispheres, respectively, when HOB was changed from flat to 30°. Significant (cohort-averaged) changes in blood velocity were not observed. Individually, varying responses to HOB manipulation were observed, including paradoxical increases in CBF with increasing HOB angle. Clinical features, stroke volume, and distance to the optical probe could not explain this paradoxical response. CONCLUSIONS: A lower HOB angle results in an increase in cortical CBF without a significant change in arterial flow velocity in AIS, but there is variability across patients in this response. Bedside CBF monitoring with diffuse correlation spectroscopy provides a potential means to individualize interventions designed to optimize CBF in AIS.

4. critical care

   Continuous Optical Monitoring of Cerebral Hemodynamics During Head-of-Bed Manipulation in Brain-Injured Adults.

   Meeri N Kim, Brian L Edlow, T Durduran, and 6 more authors

   Neurocritical Care, May 2014

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   INTRODUCTION: Head-of-bed manipulation is commonly performed in the neurocritical care unit to optimize cerebral blood flow (CBF), but its effects on CBF are rarely measured. This pilot study employs a novel, non-invasive instrument combining two techniques, diffuse correlation spectroscopy (DCS) for measurement of CBF and near-infrared spectroscopy (NIRS) for measurement of cerebral oxy- and deoxy-hemoglobin concentrations, to monitor patients during head-of-bed lowering. METHODS: Ten brain-injured patients and ten control subjects were monitored continuously with DCS and NIRS while the head-of-bed was positioned first at 30° and then at 0°. Relative CBF (rCBF) and concurrent changes in oxy- (ΔHbO2), deoxy- (ΔHb), and total-hemoglobin concentrations (ΔTHC) from left/right frontal cortices were monitored for 5 min at each position. Patient and control response differences were assessed. RESULTS: rCBF, ΔHbO2, and ΔTHC responses to head lowering differed significantly between brain-injured patients and healthy controls (P < 0.02). For patients, rCBF changes were heterogeneous, with no net change observed in the group average (0.3 ± 28.2 %, P = 0.938). rCBF increased in controls (18.6 ± 9.4 %, P < 0.001). ΔHbO2, ΔHb, and ΔTHC increased with head lowering in both groups, but to a larger degree in brain-injured patients. rCBF correlated moderately with changes in cerebral perfusion pressure (R = 0.40, P < 0.001), but not intracranial pressure. CONCLUSION: DCS/NIRS detected differences in CBF and oxygenation responses of brain-injured patients versus controls during head-of-bed manipulation. This pilot study supports the feasibility of continuous bedside measurement of cerebrovascular hemodynamics with DCS/NIRS and provides the rationale for further investigation in larger cohorts.

2013

1. modelling

   A method for choosing the smoothing parameter in a semi-parametric model for detecting change-points in blood flow

   Sung Wan Han, R C Mesquita, Theresa M Busch, and 1 more author

   Journal of Applied Statistics, May 2013

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   In a smoothing spline model with unknown change-points, the choice of the smoothing parameter strongly influences the estimation of the change-point locations and the function at the change-points. In a tumor biology example, where change-points in blood flow in response to treatment were of interest, choosing the smoothing parameter based on minimizing generalized cross-validation (GCV) gave unsatisfactory estimates of the change-points. We propose a new method, aGCV, that re-weights the residual sum of squares and generalized degrees of freedom terms from GCV. The weight is chosen to maximize the decrease in the generalized degrees of freedom as a function of the weight value, while simultaneously minimizing aGCV as a function of the smoothing parameter and the change-points. Compared with GCV, simulation studies suggest that the aGCV method yields improved estimates of the change-point and the value of the function at the change-point.

2. muscle

   Diffuse optical characterization of an exercising patient group with peripheral artery disease

   R C Mesquita, Mary Putt, Malavika Chandra, and 9 more authors

   Journal of Biomedical Optics, May 2013

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   Peripheral artery disease (PAD) is a common condition with high morbidity. While measurement of tissue oxygen saturation (S(t)O(2)) has been demonstrated, this is the first study to assess both S(t)O(2) and relative blood flow (rBF) in the extremities of PAD patients. Diffuse optics is employed to measure hemodynamic response to treadmill and pedal exercises in 31 healthy controls and 26 patients. For S(t)O(2), mild and moderate/severe PAD groups show pronounced differences compared with controls. Pre-exercise mean S(t)O(2) is lower in PAD groups by 9.3% to 10.6% compared with means of 63.5% to 66.2% in controls. For pedal, relative rate of return of S(t)O(2) to baseline is more rapid in controls (p < 0.05). Patterns of rBF also differ among groups. After both exercises, rBF tend to occur at depressed levels among severe PAD patients compared with healthy (p < 0.05); post-treadmill, rBF tend to occur at elevated levels among healthy compared with severe PAD patients (p < 0.05). Additionally, relative rate of return to baseline S(t)O(2) is more rapid among subjects with reduced levels of depression in rBF (p = 0.041), even after adjustment for ankle brachial index. This suggests a physiologic connection between rBF and oxygenation that can be measured using diffuse optics, and potentially employed as an evaluative tool in further studies.

3. modelling

   Influence of probe pressure on the diffuse correlation spectroscopy blood flow signal: extra-cerebral contributions

   R C Mesquita, Steven S Schenkel, David L Minkoff, and 8 more authors

   Biomedical Optics Express, May 2013

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   A pilot study explores relative contributions of extra-cerebral (scalp/skull) versus brain (cerebral) tissues to the blood flow index determined by diffuse correlation spectroscopy (DCS). Microvascular DCS flow measurements were made on the head during baseline and breath-holding/hyperventilation tasks, both with and without pressure. Baseline (resting) data enabled estimation of extra-cerebral flow signals and their pressure dependencies. A simple two-component model was used to derive baseline and activated cerebral blood flow (CBF) signals, and the DCS flow indices were also cross-correlated with concurrent Transcranial Doppler Ultrasound (TCD) blood velocity measurements. The study suggests new pressure-dependent experimental paradigms for elucidation of blood flow contributions from extra-cerebral and cerebral tissues.

4. spinal cord

   Optical monitoring and detection of spinal cord ischemia.

   R C Mesquita, Angela D’Souza, Thomas V Bilfinger, and 5 more authors

   Plos One, May 2013

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   Spinal cord ischemia can lead to paralysis or paraparesis, but if detected early it may be amenable to treatment. Current methods use evoked potentials for detection of spinal cord ischemia, a decades old technology whose warning signs are indirect and significantly delayed from the onset of ischemia. Here we introduce and demonstrate a prototype fiber optic device that directly measures spinal cord blood flow and oxygenation. This technical advance in neurological monitoring promises a new standard of care for detection of spinal cord ischemia and the opportunity for early intervention. We demonstrate the probe in an adult Dorset sheep model. Both open and percutaneous approaches were evaluated during pharmacologic, physiological, and mechanical interventions designed to induce variations in spinal cord blood flow and oxygenation. The induced variations were rapidly and reproducibly detected, demonstrating direct measurement of spinal cord ischemia in real-time. In the future, this form of hemodynamic spinal cord diagnosis could significantly improve monitoring and management in a broad range of patients, including those undergoing thoracic and abdominal aortic revascularization, spine stabilization procedures for scoliosis and trauma, spinal cord tumor resection, and those requiring management of spinal cord injury in intensive care settings.

5. brain modulation

   Blood flow and oxygenation changes due to low-frequency repetitive transcranial magnetic stimulation of the cerebral cortex

   R C Mesquita, Olufunsho K Faseyitan, Peter E Turkeltaub, and 8 more authors

   Journal of Biomedical Optics, May 2013

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   Transcranial magnetic stimulation (TMS) modulates processing in the human brain and is therefore of interest as a treatment modality for neurologic conditions. During TMS administration, an electric current passing through a coil on the scalp creates a rapidly varying magnetic field that induces currents in the cerebral cortex. The effects of low-frequency (1 Hz), repetitive TMS (rTMS) on motor cortex cerebral blood flow (CBF) and tissue oxygenation in seven healthy adults, during/after 20 min stimulation, is reported. Noninvasive optical methods are employed: diffuse correlation spectroscopy (DCS) for blood flow and diffuse optical spectroscopy (DOS) for hemoglobin concentrations. A significant increase in median CBF (33%) on the side ipsilateral to stimulation was observed during rTMS and persisted after discontinuation. The measured hemodynamic parameter variations enabled computation of relative changes in cerebral metabolic rate of oxygen consumption during rTMS, which increased significantly (28%) in the stimulated hemisphere. By contrast, hemodynamic changes from baseline were not observed contralateral to rTMS administration (all parameters, p>0.29). In total, these findings provide new information about hemodynamic/metabolic responses to low-frequency rTMS and, importantly, demonstrate the feasibility of DCS/DOS for noninvasive monitoring of TMS-induced physiologic effects.

2012

1. cancer

   Tumor Blood Flow Differs between Mouse Strains: Consequences for Vasoresponse to Photodynamic Therapy

   R C Mesquita, Sung Wan Han, Joann Miller, and 7 more authors

   Plos One, May 2012

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   Fluctuations in tumor blood flow are common and attributed to factors such as vasomotion or local vascular structure, yet, because vessel structure and physiology are host-derived, animal strain of tumor propagation may further determine blood flow characteristics. In the present report, baseline and stress-altered tumor hemodynamics as a function of murine strain were studied using radiation-induced fibrosacomas (RIF) grown in C3H or nude mice. Fluctuations in tumor blood flow during one hour of baseline monitoring or during vascular stress induced by photodynamic therapy (PDT) were measured by diffuse correlation spectroscopy. Baseline monitoring revealed fluctuating tumor blood flow highly correlated with heart rate and with similar median periods (i.e., ∼9 and 14 min in C3H and nudes, respectively). However, tumor blood flow in C3H animals was more sensitive to physiologic or stress-induced perturbations. Specifically, PDT-induced vascular insults produced greater decreases in blood flow in the tumors of C3H versus nude mice; similarly, during baseline monitoring, fluctuations in blood flow were more regular and more prevalent within the tumors of C3H mice versus nude mice; finally, the vasoconstrictor L-NNA reduced tumor blood flow in C3H mice but did not affect tumor blood flow in nudes. Underlying differences in vascular structure, such as smaller tumor blood vessels in C3H versus nude animals, may contribute to strain-dependent variation in vascular function. These data thus identify clear effects of mouse strain on tumor hemodynamics with consequences to PDT and potentially other vascular-mediated therapies.

2. molecular biology

   O-2 Regulates Skeletal Muscle Progenitor Differentiation through Phosphatidylinositol 3-Kinase/AKT Signaling

   Amar J Majmundar, Nicolas Skuli, R C Mesquita, and 4 more authors

   Molecular and Cellular Biology, May 2012

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   Skeletal muscle stem/progenitor cells, which give rise to terminally differentiated muscle, represent potential therapies for skeletal muscle diseases. Delineating the factors regulating these precursors will facilitate their reliable application in human muscle repair. During embryonic development and adult regeneration, skeletal muscle progenitors reside in low-O(2) environments before local blood vessels and differentiated muscle form. Prior studies established that low O(2) levels (hypoxia) maintained muscle progenitors in an undifferentiated state in vitro, although it remained unclear if progenitor differentiation was coordinated with O(2) availability in vivo. In addition, the molecular signals linking O(2) to progenitor differentiation are incompletely understood. Here we show that the muscle differentiation program is repressed by hypoxia in vitro and ischemia in vivo. Surprisingly, hypoxia can significantly impair differentiation in the absence of hypoxia-inducible factors (HIFs), the primary developmental effectors of O(2). In order to maintain the undifferentiated state, low O(2) levels block the phosphatidylinositol 3-kinase/AKT pathway in a predominantly HIF1α-independent fashion. O(2) deprivation affects AKT activity by reducing insulin-like growth factor I receptor sensitivity to growth factors. We conclude that AKT represents a key molecular link between O(2) and skeletal muscle differentiation.

3. molecular biology

   Endothelial HIF-2 alpha regulates murine pathological angiogenesis and revascularization processes

   Nicolas Skuli, Amar J Majmundar, Bryan L Krock, and 11 more authors

   Journal of Clinical Investigation, May 2012

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   Localized tissue hypoxia is a consequence of vascular compromise or rapid cellular proliferation and is a potent inducer of compensatory angiogenesis. The oxygen-responsive transcriptional regulator hypoxia-inducible factor 2α (HIF-2α) is highly expressed in vascular ECs and, along with HIF-1α, activates expression of target genes whose products modulate vascular functions and angiogenesis. However, the mechanisms by which HIF-2α regulates EC function and tissue perfusion under physiological and pathological conditions are poorly understood. Using mice in which Hif2a was specifically deleted in ECs, we demonstrate here that HIF-2α expression is required for angiogenic responses during hindlimb ischemia and for the growth of autochthonous skin tumors. EC-specific Hif2a deletion resulted in increased vessel formation in both models; however, these vessels failed to undergo proper arteriogenesis, resulting in poor perfusion. Analysis of cultured HIF-2α-deficient ECs revealed cell-autonomous increases in migration, invasion, and morphogenetic activity, which correlated with HIF-2α-dependent expression of specific angiogenic factors, including delta-like ligand 4 (Dll4), a Notch ligand, and angiopoietin 2. By stimulating Dll4 signaling in cultured ECs or restoring Dll4 expression in ischemic muscle tissue, we rescued most of the HIF-2α-dependent EC phenotypes in vitro and in vivo, emphasizing the critical role of Dll4/Notch signaling as a downstream target of HIF-2α in ECs. These results indicate that HIF-1α and HIF-2α fulfill complementary, but largely nonoverlapping, essential functions in pathophysiological angiogenesis.

4. dcs

   Validation of diffuse correlation spectroscopic measurement of cerebral blood flow using phase-encoded velocity mapping magnetic resonance imaging

   Erin M Buckley, Dalton Hance, Thomas Pawlowski, and 9 more authors

   Journal of Biomedical Optics, May 2012

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   Diffuse correlation spectroscopy (DCS) is a novel optical technique that appears to be an excellent tool for assessing cerebral blood flow in a continuous and non-invasive manner at the bedside. We present new clinical validation of the DCS methodology by demonstrating strong agreement between DCS indices of relative cerebral blood flow and indices based on phase-encoded velocity mapping magnetic resonance imaging (VENC MRI) of relative blood flow in the jugular veins and superior vena cava. Data were acquired from 46 children with single ventricle cardiac lesions during a hypercapnia intervention. Significant increases in cerebral blood flow, measured both by DCS and by VENC MRI, as well as significant increases in oxyhemoglobin concentration, and total hemoglobin concentration, were observed during hypercapnia. Comparison of blood flow changes measured by VENC MRI in the jugular veins and by DCS revealed a strong linear relationship, R=0.88, p<0.001, slope=0.91±0.07. Similar correlations were observed between DCS and VENC MRI in the superior vena cava, R=0.77, slope=0.99±0.12, p<0.001. The relationship between VENC MRI in the aorta and DCS, a negative control, was weakly correlated, R=0.46, slope=1.77±0.45, p<0.001.

2011

1. review

   Direct measurement of tissue blood flow and metabolism with diffuse optics.

   R C Mesquita, T Durduran, Guoqiang Yu, and 6 more authors

   Philosophical Transactions Royal Soc. A, Nov 2011

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   Diffuse optics has proven useful for quantitative assessment of tissue oxy- and deoxyhaemoglobin concentrations and, more recently, for measurement of microvascular blood flow. In this paper, we focus on the flow monitoring technique: diffuse correlation spectroscopy (DCS). Representative clinical and pre-clinical studies from our laboratory illustrate the potential of DCS. Validation of DCS blood flow indices in human brain and muscle is presented. Comparison of DCS with arterial spin-labelled MRI, xenon-CT and Doppler ultrasound shows good agreement (0.50<r<0.95) over a wide range of tissue types and source detector distances, corroborating the potential of the method to measure perfusion non-invasively and in vivo at the microvasculature level. All-optical measurements of cerebral oxygen metabolism in both rat brain, following middle cerebral artery occlusion, and human brain, during functional activation, are also described. In both situations, the use of combined DCS and diffuse optical spectroscopy/near-infrared spectroscopy to monitor changes in oxygen consumption by the tissue is demonstrated. Finally, recent results spanning from gene expression-induced angiogenic response to stroke care and cancer treatment monitoring are discussed. Collectively, the research illustrates the capability of DCS to quantitatively monitor perfusion from bench to bedside, providing results that match up both with literature findings and with similar experiments performed with other techniques.

2. speech

   Use of diffuse correlation spectroscopy to measure brain blood flow differences during speaking and nonspeaking tasks for fluent speakers and persons who stutter

   G M Tellis, R C Mesquita, and Arjun G Yodh

   Perspectives on Fluency and Fluency Disorders, Nov 2011

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   ... SIG 4 Perspectives on Fluency and Fluency Disorders November 2011, Vol.21, 96-106. doi: 10.1044 / ffd21 . 3.96 . SIG 4 Perspectives on Fluency and Fluency Disorders November 2011, Vol.21, 96-106. doi: 10.1044 / ffd21 . 3.96 . ... doi: 10.1044 / ffd21 . 3.96 . Download citation file: ...

3. review

   Diffuse Optics: fundamentals and tissue applications

   Rickson C. Mesquita, and Arjun G. Yodh

   In Proceedings of the International School of Physics “Enrico Fermi” Course CLXXIII “Nano Optics and Atomics: Transport of Light and Matter Waves”, Nov 2011

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   The material in this paper is different from the mainstream topics in this summer’s International School of Physics “Enrico Fermi”. It should become apparent, however, that the roots of these biomedical optics research problems share common features with much of the light scattering and transport research taught in the Varenna summer school. Here, our intention is to provide an informal review that establishes the roots of diffuse optics, and then demonstrates how diffuse optics is finding application in medicine. This paper will have two main themes. After a brief motivation of the problem, the first theme will provide a coherent discussion about light transport in turbid media. The second theme is oriented towards problems in biomedicine. As such, a short discussion of hemodynamics will be followed by representative current work from our lab, particularly with breast and brain.

2010

1. dcs

   Hemodynamic and metabolic diffuse optical monitoring in a mouse model of hindlimb ischemia

   R C Mesquita, Nicolas Skuli, Meeri N Kim, and 5 more authors

   Biomedical Optics Express, Nov 2010

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   Murine hindlimb ischemia is a useful model for investigation of the mechanisms of peripheral arterial disease and for understanding the role of endothelial cells and generic factors affecting vascular regeneration or angiogenesis. To date, important research with these models has explored tissue reperfusion following ischemia with Laser Doppler methods, methods which provide information about superficial (\textbackslashtextasciitildemm) vascular regeneration. In this work, we employ diffuse correlation spectroscopy (DCS) and diffuse optical spectroscopy (DOS) in mice after hindlimb ischemia. We hypothesize that vascular re-growth is not uniform in tissue, and therefore, since diffuse optical methods are capable of probing deep tissues, that the diffuse optics approach will provide a more complete picture of the angiogenesis process throughout the whole depth profile of the limb. Besides increased depth penetration, the combined measurements of DCS and DOS enable all-optical, noninvasive, longitudinal monitoring of tissue perfusion and oxygenation that reveals the interplay between these hemodynamic parameters during angiogenesis. Control mice were found to reestablish 90% of perfusion and oxygen consumption during this period, but oxygen saturation in the limb only partially recovered to about 30% of its initial value. The vascular recovery of mice with endothelial cell-specific deletion of HIF-2α was found to be significantly impaired relative to control mice, indicating that HIF-2α is important for endothelial cell functions in angiogenesis. Comparison of DOS/DCS measurements to parallel measurements in the murine models using Laser Doppler Flowmetry reveal differences in the reperfusion achieved by superficial versus deep tissue during neoangiogenesis; findings from histological analysis of blood vessel development were further correlated with these differences. In general, the combination of DCS and DOS enables experimenters to obtain useful information about oxygenation, metabolism, and perfusion throughout the limb. The results establish diffuse optics as a practical noninvasive method to evaluate the role of transcription factors, such as the endothelial cell-specific HIF-2α, in genetic ally modified mice.

2. connectivity

   Resting state functional connectivity of the whole head with near-infrared spectroscopy.

   R C Mesquita, Maria A Franceschini, and David A Boas

   Biomedical Optics Express, Nov 2010

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   Resting state connectivity aims to identify spontaneous cerebral hemodynamic fluctuations that reflect neuronal activity at rest. In this study, we investigated the spatial-temporal correlation of hemoglobin concentration signals over the whole head during the resting state. By choosing a source-detector pair as a seed, we calculated the correlation value between its time course and the time course of all other source-detector combinations, and projected them onto a topographic map. In all subjects, we found robust spatial interactions in agreement with previous fMRI and NIRS findings. Strong correlations between the two opposite hemispheres were seen for both sensorimotor and visual cortices. Correlations in the prefrontal cortex were more heterogeneous and dependent on the hemodynamic contrast. HbT provided robust, well defined maps, suggesting that this contrast may be used to better localize functional connectivity. The effects of global systemic physiology were also investigated, particularly low frequency blood pressure oscillations which give rise to broad regions of high correlation and mislead interpretation of the results. These results confirm the feasibility of using functional connectivity with optical methods during the resting state, and validate its use to investigate cortical interactions across the whole head.

3. imaging

   Anatomical atlas-guided diffuse optical tomography of brain activation

   Anna Custo, David A Boas, Daisuke Tsuzuki, and 5 more authors

   NeuroImage, Jan 2010

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   We describe a neuroimaging protocol that utilizes an anatomical atlas of the human head to guide diffuse optical tomography of human brain activation. The protocol is demonstrated by imaging the hemodynamic response to median-nerve stimulation in three healthy subjects, and comparing the images obtained using a head atlas with the images obtained using the subject-specific head anatomy. The results indicate that using the head atlas anatomy it is possible to reconstruct the location of the brain activation to the expected gyrus of the brain, in agreement with the results obtained with the subject-specific head anatomy. The benefits of this novel method derive from eliminating the need for subject-specific head anatomy and thus obviating the need for a subject-specific MRI to improve the anatomical interpretation of diffuse optical tomography images of brain activation.

2009

1. modelling

   Exploring neuro-vascular and neuro-metabolic coupling in rat somatosensory cortex.

   R C Mesquita, T J Huppert, and David A Boas

   Physics in Medicine and Biology, Jan 2009

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   The existence of a coupling between changes in neuronal activity, cerebral blood flow and blood oxygenation is well known. The explicit relationship between these systems, however, is complex and remains a subject of intense research. Here, we use direct electrophysiological recordings to predict blood flow and oxygenation changes measured with optical methods during parametric stimulation applied to the somatosensory cortex in rat brain. Using a multimodal model of the cerebral functional unit, we estimate a neuro-vascular and a neuro-metabolic transfer function relating the experimentally measured neural responses with the inputs to a vascular model predicting hemodynamic and blood oxygenation changes. We show that our model can accurately predict experimentally measured parametric hemodynamic evoked responses by using a single linear transfer function relationship with a reduced number of state parameters to relate the level of neural activity to evoked cerebral blood flow and oxygen metabolism changes. At the same time, we characterize the metabolic and vascular neural response functions and interpret their physiological significance.

2008

1. review

   Estudo funcional do cérebro através de NIRS e tomografia óptica de difusão

   R C Mesquita, and RJM Covolan

   In Neurociências e Epilepsia, Jan 2008

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   Resumo Espectroscopia no infravermelho próximo ( NIRS ) e tomografia óptica de difusão (DOT) são técnicas emergentes cada vez mais empregadas para o mapeamento funcional do cérebro , seja em humanos ou em animais. Estas técnicas utilizam níveis seguros de ...

2006

1. photoacoustics

   Open photoacoustic cell: Applications in plant photosynthesis studies

   R C Mesquita, A M Mansanares, E C da Silva, and 3 more authors

   Instrumentation Science & Technology, Jan 2006

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   In this article, we review the applications of the open photoacoustic cell (OPC) technique in studies of photosynthetic activity in plant leaves. The ability to perform in vivo and in situ measurements makes this technique particularly suitable for monitoring photosynthesis of plants subjected to specific treatments. Therefore, our objective in the present article is to describe, in more detail, the principles of the OPC technique and to follow the historical path of its applications related to the study of plants and photosynthesis, including recent results. It will be shown that the technique has been used to observe spectroscopic responses to herbicide application and to soil toxicity, in the study of photosynthesis induction, gas exchange, photochemical loss, photoinhibition, photosynthesis saturation, and photosynthetic responses to changes in parameters such as temperature, atmospheric conditions, and nutrient availability. Recent results have demonstrated its usefulness in the determination of the action spectrum directly from oxygen evolution measurements.

2005

1. pdt

   Terapia Fotodinâmica: uma luz na luta contra o câncer

   Joselito Nardy Ribeiro, Araceli Verónica Flores, R C Mesquita, and 2 more authors

   Physicae, Jul 2005

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   Photodynamic therapy (PDT) is a clinical treatment utilized in the therapy of cancer and others diseases. In this therapy, light-sensitive molecules, called photosensitizers, are activated by visible light generating reactive forms of oxygen. These reactive species initiate a sequence of oxidative events resulting in tumor cell death by apoptosis and/or necrosis. The purpose of this review is to present the basic principles (physical, chemical and biological) of PDT as well as its potential of application and new researches on this modality of medical therapy.

2. photoacoustics

   Photo acoustic study of plants exposed to varying light intensity growth conditions: Spectral and morphological changes

   R C Mesquita, P R Barja, E C da Silva, and 1 more author

   Journal de Physique IV, Jul 2005

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   In this paper we describe results of photo acoustic (PA) measurements carried out on various plants exposed to varying light intensity conditions. Depending on the species and light intensity conditions, the PA absorption spectra show differences in peaks associated with pigments and the cuticle. These differences are related to the spatial distribution of the pigments that differs from plant to plant. We have also performed systematic study of oxygen evolution at different wavelengths. The obtained oxygen spectra are equivalent to the action spectra usually acquired by determining the CO2 uptake and energy storage. The intensities of oxygen spectra exhibit differences depending on distinct morphology of plant.

3. photoacoustics

   Thermal diffusivity and photoacoustic spectroscopy measurements in CdTe quantum dots borosilicate glasses

   V L da Silva, R C Mesquita, E C da Silva, and 2 more authors

   Journal de Physique IV, Jul 2005

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   In this paper we describe the results of photoacoustic spectroscopy and thermal diffusivity measurements in borosilicate glass matrix with CdTe quantum dots. Samples treated at the temperature of 540°C for different periods were studied. The photoacoustic spectra show the absorption band of CdTe quantum dots, which shifts as a function of the thermal treatment time, revealing the evolution of the average radius of the nanocrystals. Thermal lens measurements provide the thermal diffusivity of the treated samples and give the behavior of the temperature coefficient of the refractive index, dn/dT, which is correlated to the transmittance spectra.

2004

1. pdt

   Construction and evaluation of a non-laser optical system for photodynamic process excitation

   R C Mesquita, E R Reis, and J H Nicola

   Acta Cirurgica Brasileira, Dec 2004

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   Purpose: To show that a non-laser light source can be constructed, using a 500 W Tungsten lamp and optical filters, and that this light source produces photodynamic effect via protoporphyrin IX (PpIX) similar to the effect produced by HeNe laser light. Methods: The broad band spectrum from a Tungsten lamp was filtered. Infrared and blue part of the spectrum was discarded by absorption process and the fraction of the spectrum, centered at the red portion, was filtered by an interference filter. Photodynamic effect was studied by the activity on endogenous PpIX of Harderian glands of Wistar rats. Twenty rats were used for the experiment. Each animal had its two Harderian gland surgically exposed, so one of them was treated with the system while the other was kept as control. After a 30 minutes period of treatment, the animals were sacrificed and their glands were removed for histological analysis. This analysis was compared to earlier published results obtained with HeNe laser light. Results: The resultant light source emission was centered around (636 ± 6.5) nm and gives up to 11.3 mW/cm² power density. It produces photodynamic effect in Harderian gland, observed either by fluorescence spectroscopy or by histological microscopy. Conclusion: There is no noticeable difference in Photodynamic effect results if activated by HeNe laser or by the proposed non-laser light source emitting at the red portion of the spectrum.