Oxygen Consumption In Vivo by Ultra-High Dose Rate Electron Irradiation Depends Upon Baseline Tissue Oxygenation.

Purpose: This study aimed to assess the impact of tissue oxygen levels on transient oxygen consumption induced by ultra-high dose rate (UHDR) electron radiation in murine flank and to examine the effect of dose rate variations on this relationship.

Methods And Materials: Real-time oximetry using the phosphorescence quenching method and Oxyphor PdG4 molecular probe was employed. Continuous measurements were taken during radiation delivery on a UHDR-capable Mobetron linear accelerator.

Disruption of intestinal oxygen balance in acute colitis alters the gut microbiome.

The juxtaposition of well-oxygenated intestinal colonic tissue with an anerobic luminal environment supports a fundamentally important relationship that is altered in the setting of intestinal injury, a process likely to be relevant to diseases such as inflammatory bowel disease. Herein, using two-color phosphorometry to non-invasively quantify both intestinal tissue and luminal oxygenation in real time, we show that intestinal injury induced by DSS colitis reduces intestinal tissue oxygenation in a spatially defined manner and increases the flux of oxygen from the tissue into the gut lumen. By characterizing the composition of the microbiome in both DSS colitis-affected gut and in a bioreactor containing a stable human fecal community exposed to microaerobic conditions, we provide evidence that the increased flux of oxygen into the gut lumen augments glycan degrading bacterial taxa rich in glycoside hydrolases which are known to inhabit gut mucosal surface.

Bilateral nephrectomy impairs cardiovascular function and cerebral perfusion in a rat model of acute hemodilutional anemia.

Anemia and renal failure are independent risk factors for perioperative stroke, prompting us to assess the combined impact of acute hemodilutional anemia and bilateral nephrectomy (2Nx) on microvascular brain Po (Po) in a rat model. Changes in Po (phosphorescence quenching) and cardiac output (CO, echocardiography) were measured in different groups of anesthetized Sprague-Dawley rats (1.5% isoflurane, = 5-8/group) randomized to Sham 2Nx or 2Nx and subsequently exposed to acute hemodilutional anemia (50% estimated blood volume exchange with 6% hydroxyethyl starch) or time-based controls (no hemodilution).

CHEX-seq detects single-cell genomic single-stranded DNA with catalytical potential.

Genomic DNA (gDNA) undergoes structural interconversion between single- and double-stranded states during transcription, DNA repair and replication, which is critical for cellular homeostasis. We describe "CHEX-seq" which identifies the single-stranded DNA (ssDNA) in situ in individual cells. CHEX-seq uses 3'-terminal blocked, light-activatable probes to prime the copying of ssDNA into complementary DNA that is sequenced, thereby reporting the genome-wide single-stranded chromatin landscape.

On the circularly polarized luminescence of individual triplet sublevels.

We discuss the possibility of using circularly polarized luminescence (CPL) as a tool to probe individual triplet spin sublevels that are populated nonadiabatically following photoexcitation. This study is motivated by a mechanism proposed for chirality-induced spin selectivity in which coupled electronic-nuclear dynamics may lead to a non-statistical population of the three triplet sublevels in chiral systems. We find that low-temperature CPL should aid in quantifying the exact spin state/s populated through coupled electronic-nuclear motion in chiral molecules.

Direct Measurements of FLASH-Induced Changes in Intracellular Oxygenation.

Purpose: The goal of our study was to characterize the dynamics of intracellular oxygen during application of radiation at conventional (CONV) and FLASH dose rates and obtain evidence for or against the oxygen depletion hypothesis as a mechanism of the FLASH effect.

Methods And Materials: The measurements were performed by the phosphorescence quenching method using probe Oxyphor PtG4, which was delivered into the cellular cytosol by electroporation.

Results: Intracellular radiochemical oxygen depletion (ROD) g-value for a dose rate of 100 Gy/s in the normoxic range was found to be 0.

Surgical Inflammation Alters Immune Response to Intraoperative Photodynamic Therapy.

Unlabelled: Surgical cytoreduction for patients with malignant pleural mesothelioma (MPM) is used for selected patients as a part of multi-modality management strategy. Our group has previously described the clinical use of photodynamic therapy (PDT), a form of non-ionizing radiation, as an intraoperative therapy option for MPM. Although necessary for the removal of bulk disease, the effects of surgery on residual MPM burden are not understood.

Naphthodithiophene-Fused Porphyrins: Synthesis, Characterization, and Impact of Extended Conjugation on Aromaticity.

The fusion of tetrapyrroles with aromatic heterocycles constitutes a useful tool for manipulating their opto-electronic properties. In this work, the synthesis of naphthodithiophene-fused porphyrins was achieved through a Heck reaction-based cascade of steps followed by the Scholl reaction. The naphthodithiophene-fused porphyrins display a unique set of optical and electronic properties.

Aerobic exercise reverses aging-induced depth-dependent decline in cerebral microcirculation.

Aging is a major risk factor for cognitive impairment. Aerobic exercise benefits brain function and may promote cognitive health in older adults. However, underlying biological mechanisms across cerebral gray and white matter are poorly understood.

Spin-Orbit versus Hyperfine Coupling-Mediated Intersystem Crossing in a Radical Pair.

While spin-orbit coupling (SOC) is typically the dominant interaction that couples singlet and triplet states within individual chromophores, hyperfine coupling (HFC) becomes important in multichromophoric systems, particularly in relation to the radical pair mechanism. Here, we use TD-DFT to calculate the spin-orbit coupling and hyperfine coupling between the first singlet and triplet charge transfer states of the radical pair Pyrene and ,-dimethylaniline. We show that, as the intermolecular donor-acceptor distance grows, SOC decays to zero (as one would expect) because singlet and triplet states are characterized by identical orbitals in space, while the HFC remains comparatively constant.

Aerobic exercise reverses aging-induced depth-dependent decline in cerebral microcirculation.

Aging is a major risk factor for cognitive impairment. Aerobic exercise benefits brain function and may promote cognitive health in older adults. However, underlying biological mechanisms across cerebral gray and white matter are poorly understood.

Measurements of cerebral microvascular blood flow, oxygenation, and morphology in a mouse model of whole-brain irradiation-induced cognitive impairment by two-photon microscopy and optical coherence tomography: evidence for microvascular injury in the cerebral white matter.

Whole-brain irradiation (WBI, also known as whole-brain radiation therapy) is a mainstay treatment modality for patients with multiple brain metastases. It is also used as a prophylactic treatment for microscopic tumors that cannot be detected by magnetic resonance imaging. WBI induces a progressive cognitive decline in ~ 50% of the patients surviving over 6 months, significantly compromising the quality of life.

Altered hemodynamics and vascular reactivity in a mouse model with severe pericyte deficiency.

Pericytes are the mural cells of the microvascular network that are in close contact with underlying endothelial cells. Endothelial-secreted PDGFB leads to recruitment of pericytes to the vessel wall, but this is disrupted in mice when the PDGFB retention motif is deleted. This results in severely reduced pericyte coverage on blood vessels.

Real-time tracking of brain oxygen gradients and blood flow during functional activation.

Significance: Cerebral metabolic rate of oxygen ( ) consumption is a key physiological variable that characterizes brain metabolism in a steady state and during functional activation.

Aim: We aim to develop a minimally invasive optical technique for real-time measurement of concurrently with cerebral blood flow (CBF).

Approach: We used a pair of macromolecular phosphorescent probes with nonoverlapping optical spectra, which were localized in the intra- and extravascular compartments of the brain tissue, thus providing a readout of oxygen gradients between these two compartments.

Unusual Reactivity and Metal Affinity of Water-Soluble Dipyrrins.

Dipyrrins are a versatile class of organic ligands capable of fluorogenic complexation of metal ions. The primary goal of our study was to evaluate dipyrrins functionalized with ester and amide groups in 2,2'-positions in sensing applications. While developing the synthesis, we found that 3,3',4,4'-tetraalkyldipyrrins 2,2'-diesters as well as 2,2'-diamides can undergo facile addition of water at the -bridge, transforming into colorless -hydroxydipyrromethanes.

Oxygen Monitoring in Model Solutions and In Vivo in Mice During Proton Irradiation at Conventional and FLASH Dose Rates.

FLASH is a high-dose-rate form of radiation therapy that has the reported ability, compared with conventional dose rates, to spare normal tissues while being equipotent in tumor control, thereby increasing the therapeutic ratio. The mechanism underlying this normal tissue sparing effect is currently unknown, however one possibility is radiochemical oxygen depletion (ROD) during dose delivery in tissue at FLASH dose rates. In order to investigate this possibility, we used the phosphorescence quenching method to measure oxygen partial pressure before, during and after proton radiation delivery in model solutions and in normal muscle and sarcoma tumors in mice, at both conventional (Conv) (∼0.

Measurement of cerebral oxygen pressure in living mice by two-photon phosphorescence lifetime microscopy.

The ability to quantify partial pressure of oxygen (pO) is of primary importance for studies of metabolic processes in health and disease. Here, we present a protocol for imaging of oxygen distributions in tissue and vasculature of the cerebral cortex of anesthetized and awake mice. We describe two-photon phosphorescence lifetime microscopy (2PLM) of oxygen using the probe Oxyphor 2P.

Neurophotonic tools for microscopic measurements and manipulation: status report.

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, ' 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.

Ultrafast Tracking of Oxygen Dynamics During Proton FLASH.

Purpose: Radiation therapy delivered at ultrafast dose rates, known as FLASH RT, has been shown to provide a therapeutic advantage compared with conventional radiation therapy by selectively protecting normal tissues. Radiochemical depletion of oxygen has been proposed to underpin the FLASH effect; however, experimental validation of this hypothesis has been lacking, in part owing to the inability to measure oxygenation at rates compatible with FLASH.

Methods And Materials: We present a new variant of the phosphorescence quenching method for tracking oxygen dynamics with rates reaching up to ∼3.

Quantification of Oxygen Depletion During FLASH Irradiation In Vitro and In Vivo.

Purpose: Delivery of radiation at ultrahigh dose rates (UHDRs), known as FLASH, has recently been shown to preferentially spare normal tissues from radiation damage compared with tumor tissues. However, the underlying mechanism of this phenomenon remains unknown, with one of the most widely considered hypotheses being that the effect is related to substantial oxygen depletion upon FLASH, thereby altering the radiochemical damage during irradiation, leading to different radiation responses of normal and tumor cells. Testing of this hypothesis would be advanced by direct measurement of tissue oxygen in vivo during and after FLASH irradiation.

-Diarylphthalimidoporphyrins: Effects of Symmetry Breaking on Two-Photon Absorption and Linear Photophysical Properties.

Aromatically π-extended porphyrins possess exceptionally intense one-photon (1P) and sometimes two-photon (2P) absorption bands, presenting interest for construction of optical imaging probes and photodynamic agents. Here we investigated how breaking the molecular symmetry affects linear and 2PA properties of π-extended porphyrins. First, we developed the synthesis of porphyrins fused with two phthalimide fragments, termed -diarylphthalimidoporphyrins (DAPIP).

Review of in vivo optical molecular imaging and sensing from x-ray excitation.

Significance: Deep-tissue penetration by x-rays to induce optical responses of specific molecular reporters is a new way to sense and image features of tissue function in vivo. Advances in this field are emerging, as biocompatible probes are invented along with innovations in how to optimally utilize x-ray sources.

Aim: A comprehensive review is provided of the many tools and techniques developed for x-ray-induced optical molecular sensing, covering topics ranging from foundations of x-ray fluorescence imaging and x-ray tomography to the adaptation of these methods for sensing and imaging in vivo.

Three-Photon Spectroscopy of Porphyrins.

Recent advances in laser technology have made three-photon (3P) microscopy a real possibility, raising interest in the phenomenon of 3P absorption (3PA). Understanding 3PA of organic chromophores is especially important in view of those imaging applications that rely on exogenous probes, whose optical properties can be manipulated and optimized. Here, we present measurements and theoretical analysis of the degenerate 3PA spectra of several phosphorescent metalloporphyrins, which are used in the construction of biological oxygen probes.

Implantable sensor for local Cherenkov-excited luminescence imaging of tumor pO2 during radiotherapy.

Significance: The necessity to use exogenous probes for optical oxygen measurements in radiotherapy poses challenges for clinical applications. Options for implantable probe biotechnology need to be improved to alleviate toxicity concerns in human use and facilitate translation to clinical trial use.

Aim: To develop an implantable oxygen sensor containing a phosphorescent oxygen probe such that the overall administered dose of the probe would be below the Federal Drug Administration (FDA)-prescribed microdose level, and the sensor would provide local high-intensity signal for longitudinal measurements of tissue pO2.