Minori Masaki

Background: Sleep-disordered breathing (SDB) is an established adverse prognostic factor in heart failure (HF). Sleep apnea-specific hypoxic burden (SASHB), which reflects the duration and depth of respiratory event–related oxygen desaturation, has shown stronger prognostic value than the apnea-hypopnea index (AHI) in general populations and patients with coronary artery disease. However, its clinical utility in patients hospitalized due to acute HF remains unclear. Objectives: This study evaluated the prognostic value of SASHB in patients hospitalized for acute HF and compared its performance with AHI for risk stratification and identification of patients who may benefit from positive airway pressure (PAP) therapy. Methods: This post hoc analysis included 230 patients from a prospective single-center observational cohort of adults hospitalized for acute HF. The primary analysis included 178 patients who did not receive PAP treatment. Associations of SASHB and AHI with the composite endpoint of cardiovascular death or rehospitalization for worsening HF were evaluated using Cox proportional hazards models. Model improvement after adding SASHB or AHI to a model including established clinical risk factors was assessed using changes in the C index and Brier score, reflecting changes in model discrimination and prediction error, respectively. In the full cohort, the interaction between PAP treatment and SDB metrics was evaluated using the g-formula. Results: During a median follow-up of 3.7 years, 58 of 178 patients (32.6%) reached the composite endpoint. Both SASHB and AHI were independently associated with the composite outcome after multivariable adjustment. However, only SASHB consistently predicted outcomes across analyses and improved model performance beyond established prognostic factors (bootstrap ΔC index, 0.020 [95% CI: 0.008–0.031]; bootstrap ΔBrier score, −0.007 [95% CI: −0.014 to −0.001]), whereas AHI did not. In the analysis including PAP-treated patients, both SASHB and AHI showed interaction with PAP treatment. Conclusions: In patients hospitalized for acute HF, SASHB showed a consistent independent association with adverse clinical outcomes and provided additional prognostic information beyond AHI. SASHB may improve risk stratification and may help identify patients who are more likely to benefit from PAP therapy.

Coherent Raman imaging (CRI) enables label-free chemical imaging based on intrinsic molecular vibrations, but its applicability is often limited by low sensitivity, hindering the detection of low-abundance biomolecules. Although electronic resonance enhances sensitivity, most resonance CRI implementations rely on narrowband excitation and/or detection, which limits spectral coverage and complicates the differentiation of target molecules from complex backgrounds. Here, we address these challenges by developing broadband electronic resonance coherent anti-Stokes/Stokes Raman scattering (BER-CARS/CSRS) microscopy. We show that BER-CARS/CSRS enables highly sensitive, label-free imaging of endogenous chromophores with broad spectral coverage of the entire fingerprint region. Specifically, we captured time-lapse images, visualizing low-abundance cytochromes alongside abundant biomolecules (lipids, proteins, and nucleic acids) in living human embryonic kidney (HEK) 293 cells. Furthermore, we applied the method to mouse tissues, highlighting characteristic localizations of cytochromes in the brain cortex, the cerebral ventricle wall, and the liver. Our results demonstrate that BER-CARS/CSRS provides highly sensitive, label-free chemical imaging from organelle dynamics to tissue mapping, enabling quantitative phenotyping and slide-scale histopathology.

Coumarin-hemicyanine (CHC) hybrid fluorophores bearing an intramolecular nucleophile have been reported as ratiometric fluorescent probes based on the equilibrium between the π-conjugated open and cyclic closed forms. Here, we report red-shifted CHC derivatives that can serve as scaffold dyes of activated fluorescent probes and activated Raman probes. We prepared a series of cyano-substituted CHC derivatives and found that substitution at C-4 of the coumarin moiety is effective in extending the absorption wavelength. The near-infrared (NIR) emission of these 4CN-CHC derivatives exhibits high tissue penetration. Dual-color imaging with 4CN-CHC enabled ratiometric monitoring of the lysosomal pH changes. Furthermore, the coherent anti-Stokes Raman scattering (CARS) signals of 4CN-CHC derivatives could be regulated by modifying the open/closed equilibrium, and the different patterns of CARS spectra enabled us to perform multicomponent imaging. Thus, these 4CN-CHC derivatives expand the repertoire of functional probes for NIR and multiplexed vibrational imaging.

Lipids constitute approximately half of the dry weight of the brain and play a crucial role in the rapid conduction of action potentials and neurotransmission. However, the maturation of the lipid composition underlying complex brain functions matures during development remains unclear. We developed a sensitive coherent Raman spectroscopic imaging system in which the laser beam is always aligned with the optical axis of the microscope. This system enables seamless stitching-free imaging with a scalable field-of-view and broadband wavelength coverage. Using this unique combination system, we analyzed temporal and spatial changes in lipid composition from the fetal stage to adulthood across mouse brain regions. Our findings revealed that regions with a high total lipid ratio gradually expanded throughout the brain during size growth. While the total lipid ratio continuously increased, changes in lipid composition, particularly ceramide accumulation, were observed in the fiber regions during periods of increasing axonal myelination. High-resolution coherent Raman imaging of the fetal brain revealed that radial glial cells (the most undifferentiated cells) exhibited a higher total lipid ratio than the more differentiated cells. These results can be detected using this system and provide fundamental insights into lipid maturation across different brain regions and developmental stages.