Neurophotonics最新文献

Introduction: Disorders of consciousness (DoCs) are characterized by varying levels of arousal and awareness. Due to severe motor impairments often accompanying these conditions, differentiating between minimally conscious state (MCS) and unresponsive wakefulness syndrome (UWS) remains challenging. Accurate diagnosis, however, is critical for optimal treatment and prognosis. Functional near-infrared spectroscopy (fNIRS), due to its portability and noninvasiveness, holds promise for brain-based diagnostics, although current methods lack sufficient sensitivity and specificity.

Methods: We introduce a highly sensitive, and specific fNIRS-based diagnostic approach tailored to the individual cognitive state of DoC patients. Nine healthy participants received auditory cues instructing them to either perform individually tailored motor-speech imagery or remain at rest. In separate runs, participants were instructed to be responsive to these cues to mimic MCS, or unresponsive, to mimic UWS. fNIRS-channel covariance matrices were classified for responsive and unresponsive states as either imagery or rest using a Riemannian-geometry-based approach.

Results: Classification between responsive and unresponsive states achieved a sensitivity of 100% and a specificity of 89% across participants. Within the two states, imagery and rest were classified with 83,9% and 55,93% accuracy, respectively; the latter result, close to chance level, was expected in the unresponsive state.

Conclusion: This individualized diagnostic approach may have the potential to significantly enhance diagnostic accuracy for DoCs. It provides a noninvasive, efficient, and objective assessment, potentially reducing the rate of misdiagnosis rates. The practicality and minimal technical requirements of fNIRS further support future clinical implementation.

Significance: The use of functional near-infrared spectroscopy (fNIRS) is expanding, including examples of devices approved for routine clinical use for specific indications. Instrument standardization is a critical element to facilitate clinical adoption. Currently, there is no published description of a phantom that meets the requirements of IEC 80601-2-71, the IEC/ISO standard for fNIRS equipment.

Aim: We report an example of the implementation of the fNIRS standard phantom described in IEC 80601-2-71. We further report results from measurement campaigns with this phantom prototype in Japan and Europe.

Approach: A phantom prototype was built and circulated among multiple academic and commercial fNIRS groups with diverse instrumentation. The phantom prototype was characterized by wavelength-dependent measurements of its diffuse optical features and utilized in a test for fNIRS signal magnitude as described in IEC 80601-2-71.

Results: The optical loss of this phantom prototype as well as its change by varying an internal aperture were found to be $\sim 40\mathrm{dB}$ and between 3.5 and 3.6 dB, respectively. The test for fNIRS signal magnitude based on this phantom was successfully carried out on various commercial fNIRS devices.

Conclusions: The characteristics of the phantom prototype agreed with the specifications in the standard. The phantom prototype proved suitable for the related test in IEC 80601-2-71.

Significance: Recent evidence highlights significant heterogeneity of the blood-brain barrier (BBB) across vascular types, which becomes more pronounced under disease conditions. However, functional changes in vascular-type-dependent BBB leakage remain poorly characterized.

Aim: We aimed to establish an analysis framework for quantifying single-vessel BBB total leakage and identifying vascular-type-dependent patterns of total leakage change in disease states.

Approach: We introduce a method that combines in vivo real-time two-photon imaging with uniform manifold approximation and projection (UMAP)-based dimensionality reduction to assess BBB total leakage at the single-vessel level. Two rodent models were used, pilocarpine-induced status epilepticus (SE) and lipopolysaccharide-induced neuroinflammation (NI), which exhibit differential pathophysiological characteristics of BBB impairment.

Results: Real-time imaging clearly showed arterial BBB leakage in SE, whereas leakage in NI was likely venous. Conventional intensity-based metrics, including area under the curve (AUC), intensity fold change ( $\Delta F/F_0$ ), and averaged differential coefficient ( $\Delta F/\Delta t$ ), detected arteria-specific changes in SE but failed to capture vein-specific differences in NI. By contrast, UMAP-based analyses sensitively distinguished disease-specific total leakage patterns, allowing separation of SE from arterial data and NI from venous data.

Conclusions: This integrated approach enables quantitative evaluation of vascular-type-dependent BBB total leakage and provides a platform for future studies on vessel-specific BBB alterations in neurological disorders.

[This corrects the article DOI: 10.1117/1.NPh.12.3.035006.].

Significance: Cerebral autoregulation (CA) relies on cerebrovascular reactivity, and it is often impaired after acute brain injury (ABI), contributing to secondary brain damage. Noninvasive neuromonitoring with near-infrared spectroscopy (NIRS) can detect oscillations in cerebral hemodynamics, which may reflect autoregulatory function and may therefore be a candidate biomarker for CA monitoring.

Aim: We investigated whether changes in the spectral composition of the NIRS signal in ABI under the condition of mild hyperoxia are associated with clinical outcomes in ABI patients.

Approach: Bilateral prefrontal NIRS recording was performed during hyperoxia challenges in mechanically ventilated ABI patients admitted to the neurocritical care unit. Spectral power in low-frequency and very low-frequency oscillations (VLFO) was computed and correlated with clinical scores and functional outcomes (Glasgow Outcome Scale).

Results: Patients with favorable outcomes exhibited increased VLFO during mild hyperoxia with a fraction of inspired oxygen ( ${\mathrm{FiO}}_2$ ) of 50%, whereas no further rise occurred at ${\mathrm{FiO}}_2$ 70%, likely due to oxygen-induced vasoconstriction. In a subgroup of patients with subarachnoid hemorrhage, VLFO changes correlated with clinical severity and independently predicted outcome.

Conclusions: Our preliminary findings in a group of 20 patients suggest a potential role of NIRS in the development of individualized neuromonitoring strategies for brain-injured patients.

The editorial reflects on the secret ingredients that can elevate the flavor of our scientific ideas.

Significance: Functional near-infrared spectroscopy (fNIRS) is a noninvasive technique commonly used to examine cognitive functions such as working memory (WM). However, fNIRS signals are often interfered with by extracerebral activity, such as scalp hemodynamics. Short separation channels (SSCs) allow direct measurement of these signals. Short-channel regression (SCR) is widely used to reduce scalp interference, but its added value in WM paradigms remains underexplored.

Aim: We aimed to examine the effect of SCR on improving the validity of fNIRS measurements for WM load (WML).

Approach: We used the $N$ -Back task to induce WML-dependent brain activation by varying the " $n$ " level. Data from 20 participants were collected using fNIRS with SSC. Hemodynamic responses were analyzed with generalized linear models and linear mixed models to assess SCR's effect on the sensitivity of cortical activation measures.

Results: SCR enhanced the statistical effects of $N$ -Back levels on measured hemodynamic responses at both group and subject levels, improving the validity and sensitivity of fNIRS.

Conclusions: SCR improves fNIRS measurement sensitivity and validity, even in tasks with minimal motor requirements.

Significance: Although genetically encoded sensors have advanced the study of cortical excitation, tools for large-scale imaging of inhibition remain limited. Visualizing extracellular gamma-aminobutyric acid (GABA) dynamics in vivo is essential for understanding how inhibitory networks shape brain activity across sensory, behavioral, and pharmacological states.

Aim: Our aims are to validate and apply the genetically encoded sensor iGABASnFR2 for wide-field imaging of extracellular GABA and to characterize how cortical inhibition reorganizes across brain states, sensory modalities, and after GABA transporter blockade.

Approach: We performed mesoscale imaging in head-fixed C57BL/6 mice systemically expressing iGABASnFR2. Recordings were conducted under isoflurane anesthesia, during quiet wakefulness, natural sleep [non-rapid eye movement (NREM) and rapid eye movement], and after administration of the GAT-1 inhibitor tiagabine. We analyzed both sensory-evoked and spontaneous GABA signals using time-series, spectral, and seed-pixel correlation analyses.

Results: iGABASnFR2 demonstrated strong and modality-specific GABAergic responses to sensory stimulation, with faster and stronger activation in the contralateral cortex. Although the general spatial patterns of sensory-evoked GABA responses were consistent across anesthesia and quiet wakefulness, the amplitude, timing, and spread of these responses were significantly greater during wakefulness. During spontaneous activity, cortical GABA levels and connectivity modulated by brain state: GABA amplitude and interhemispheric synchrony, were highest during quiet wakefulness but reduced during NREM sleep. Tiagabine elevated baseline GABA levels, abolished stimulus-evoked responses, and enhanced local and long-range inhibitory synchrony.

Conclusions: iGABASnFR2 enables reliable, high-resolution imaging of cortical GABA dynamics in vivo. These results demonstrate that inhibitory signaling is dynamically structured across brain states and can be pharmacologically modulated. This tool offers opportunities to explore the role of inhibition in health and disease at the mesoscale level.

Ganesh Vasan (University of Minnesota) interviewed Mark Schnitzer (Stanford University) about his pioneering work in brain imaging across scales.

Significance: The effects of repetitive head impacts through contact sport participation remain poorly understood. Longitudinal assessments of their influence on neurophysiological and cognitive-motor changes can provide insights into brain function and athlete health.

Aim: We aimed to quantify the effects of repetitive head impact exposure from a season of ice hockey participation on cortical neurophysiology during single- and dual-task standing balance tasks.

Approach: We compared frontopolar oxyhemoglobin concentration changes longitudinally during standing balance tasks using functional near-infrared spectroscopy. Similarly, we compared motor performance from postural assessments, quantified through inertial measurement units. To quantify cognitive performance, serial-7 subtraction task accuracy was recorded.

Results: Following a season of contact sport, increased frontopolar cortex activity was observed during both single- and dual-task postural tasks. In addition, longitudinal increases in transverse and coronal sway velocities were observed. Despite these changes in neurophysiology and postural control, cognitive task performance (serial-7 subtraction) remained unchanged from pre- to postseason.

Conclusions: Contact sport participation alters cortical neurophysiology and cognitive-motor performance, with more pronounced longitudinal changes in frontopolar prefrontal cortex activity during weight-bearing cognitive tasks.