Jason Sutin

Tumor–immune interactions evolve dynamically within heterogeneous tumor microenvironments, yet methods for repeatedly measuring multiple cellular phenotypes in vivo remain limited. We developed multiplexed video hyperspectral microendoscopy to image fluorescently labeled tumor and immune cell biomarkers in living tissue at cellular resolution. The platform combines photon-efficient spectral detection with rapid spectral unmixing to resolve cocktails of antibody and ligand probes and quantify multiple tumor and immune biomarkers simultaneously in vivo . In mouse tumor models, longitudinal imaging revealed spatially organized tumor and immune cell phenotypes and quantified treatment-associated changes within individual animals. Wide-field mosaics extended the microendoscopic field of view to map biomarker heterogeneity across tumors. These results establish video hyperspectral microendoscopy as a platform for longitudinal measurement of spatially structured tumor–immune dynamics in vivo .

Infant hydrocephalus poses a severe global health burden; 80% of cases occur in the developing world where patients have limited access to neurosurgical care. Surgical treatment combining endoscopic third ventriculostomy and choroid plexus cauterization (ETV/CPC), first practiced at CURE Children’s Hospital of Uganda (CCHU), is as effective as standard ventriculoperitoneal shunt (VPS) placement while requiring fewer resources and less post-operative care. Although treatment focuses on controlling ventricle size, this has little association with treatment failure or long-term outcome. This study aims to monitor the progression of hydrocephalus and treatment response, and investigate the association between cerebral physiology, brain growth, and neurodevelopmental outcomes following surgery. We will enroll 300 infants admitted to CCHU for treatment. All patients will receive pre/post-operative measurements of cerebral tissue oxygenation (SO₂), cerebral blood flow (CBF), and cerebral metabolic rate of oxygen consumption (CMRO₂) using frequency-domain near-infrared combined with diffuse correlation spectroscopies (FDNIRS-DCS). Infants will also receive brain imaging, to monitor tissue/ventricle volume, and neurodevelopmental assessments until two years of age. This study will provide a foundation for implementing cerebral physiological monitoring to establish evidence-based guidelines for hydrocephalus treatment. This paper outlines the protocol, clinical workflow, data management, and analysis plan of this international, multi-center trial.

Cerebrospinal fluid (CSF) provides vital support for the brain. Abnormal CSF accumulation is deleterious for perinatal neurodevelopment, but how CSF leaves the brain during this critical period is unknown. We found in mice a postnatal neurodevelopmental transition phase featuring precipitous CSF K ⁺ clearance, accompanied by water, through the choroid plexus (ChP). The period corresponds to a human fetal stage when canonical CSF clearance pathways have yet to form and congenital hydrocephalus begins to manifest. Unbiased ChP metabolic and ribosomal profiling highlighted this transition phase with increased ATP yield and activated energy-dependent K ⁺ transporters, in particular the Na ⁺ -K ⁺ -Cl ⁻ and water cotransporter NKCC1. ChP-targeted NKCC1 overexpression enhanced K ⁺ -driven CSF clearance and enabled more permissive cerebral hydrodynamics. Moreover, ventriculomegaly in an obstructive hydrocephalus model was improved by ChP-targeted NKCC1 overexpression. Collectively, we identified K ⁺ -driven CSF clearance through ChP during a transient but critical neurodevelopmental phase, with translational value for pathologic conditions.

Corrected disclosures for the article “Prolonged monitoring of cerebral blood flow and autoregulation with diffuse correlation spectroscopy in neurocritical care patients.” This article [Neurophotonics 5, 045005 (2018) doi: 10.1117/1.NPh.5.4.045005] was originally published online on 13 November 2018 with an error in the Disclosures section, where information regarding potential conflicts of interest was reported incompletely. Original: The authors hold patents on the DCS technology. MAF has a financial interest in 149 Medical, Inc., a company developing DCS technology for assessing and monitoring cerebral blood flow in newborn infants. MAF’s interests were reviewed and are managed by Massachusetts General Hospital and Partners HealthCare in accordance with their conflict of interest policies. Corrected: MAF and DAB have financial interest in 149 Medical, Inc., a company developing DCS technology for assessing and monitoring cerebral blood flow in newborn infants, and in Dynometrics, Inc., a company that makes devices that use NIRS technology for athletes to evaluate muscle performance. MAF and DAB interests were reviewed and are managed by Massachusetts General Hospital and Partners HealthCare in accordance with their conflict of interest policies. This article was corrected online on 11 February 2020.

Monitoring of cerebral blood flow (CBF) and autoregulation are essential components of neurocritical care, but continuous noninvasive methods for CBF monitoring are lacking. Diffuse correlation spectroscopy (DCS) is a noninvasive diffuse optical modality that measures a CBF index (CBF_i) in the cortex microvasculature by monitoring the rapid fluctuations of near-infrared light diffusing through moving red blood cells. We tested the feasibility of monitoring CBF_i with DCS in at-risk patients in the Neurosciences Intensive Care Unit. DCS data were acquired continuously for up to 20 h in six patients with aneurysmal subarachnoid hemorrhage, as permitted by clinical care. Mean arterial blood pressure was recorded synchronously, allowing us to derive autoregulation curves and to compute an autoregulation index. The autoregulation curves suggest disrupted cerebral autoregulation in most patients, with the severity of disruption and the limits of preserved autoregulation varying between subjects. Our findings suggest the potential of the DCS modality for noninvasive, long-term monitoring of cerebral perfusion, and autoregulation.

We present a microfabricated, continuous-flow, turbulent mixing device that can mix two or more fluids to complete homogeneity on the molecular scale in the microsecond range. The current design is compact, portable, relatively simple to fabricate, adaptable for various measurement techniques, and consumes small sample volumes. The entire mixing process is observable and we use this feature to characterize the dependence of the progress of mixing on the flow velocity. We present details of the mixer’s construction and optical data acquisition using fluorescence. Because the mixer is constructed using microfabrication technology, it is inexpensive and alterations are easy to explore. We show that the dependence of mixing times and pressure drop on the flow velocity agree well with theoretical expectations for turbulent pipe flow. This provides useful guidelines in predicting performance of this type of mixing device.