MRI evaluation of cerebral metabolic rate of oxygen (CMRO) in obstructive sleep apnea.

Patients with obstructive sleep apnea (OSA) are at elevated risk of developing systemic vascular disease and cognitive dysfunction. Here, cerebral oxygen metabolism was assessed in patients with OSA by means of a magnetic resonance-based method involving simultaneous measurements of cerebral blood flow rate and venous oxygen saturation in the superior sagittal sinus for a period of 10 minutes at an effective temporal resolution of 1.3 seconds before, during, and after repeated 24-second breath-holds mimicking spontaneous apneas, yielding, along with pulse oximetry-derived arterial saturation, whole-brain CMRO via Fick's Principle.

Endogenous T1ρ cardiovascular magnetic resonance in hypertrophic cardiomyopathy.

Background: Hypertrophic cardiomyopathy (HCM) is characterized by increased left ventricular wall thickness, cardiomyocyte hypertrophy, and fibrosis. Adverse cardiac risk characterization has been performed using late gadolinium enhancement (LGE), native T1, and extracellular volume (ECV). Relaxation time constants are affected by background field inhomogeneity.

Co-delivery of etoposide and cisplatin in dual-drug loaded nanoparticles synergistically improves chemoradiotherapy in non-small cell lung cancer models.

Chemoradiotherapy with cisplatin and etoposide is a curative management regimen for both small and non-small cell lung cancers. While the treatment regimen is effective, it also has a high toxicity profile. One potential strategy to improve the therapeutic ratio of chemoradiation is to utilize nanotherapeutics.

Calibrated fMRI for dynamic mapping of CMRO responses using MR-based measurements of whole-brain venous oxygen saturation.

Functional MRI (fMRI) can identify active foci in response to stimuli through BOLD signal fluctuations, which represent a complex interplay between blood flow and cerebral metabolic rate of oxygen (CMRO) changes. Calibrated fMRI can disentangle the underlying contributions, allowing quantification of the CMRO response. Here, whole-brain venous oxygen saturation () was computed alongside ASL-measured CBF and BOLD-weighted data to derive the calibration constant, , using the proposed -based calibration.

MRI evaluation of cerebrovascular reactivity in obstructive sleep apnea.

Obstructive sleep apnea (OSA) is characterized by intermittent obstruction of the airways during sleep. Cerebrovascular reactivity (CVR) is an index of cerebral vessels' ability to respond to a vasoactive stimulus, such as increased CO. We hypothesized that OSA alters CVR, expressed as a breath-hold index (BHI) defined as the rate of change in CBF or BOLD signal during a controlled breath-hold stimulus mimicking spontaneous apneas by being both hypercapnic and hypoxic.

Nanoparticle co-delivery of wortmannin and cisplatin synergistically enhances chemoradiotherapy and reverses platinum resistance in ovarian cancer models.

Most ovarian cancer patients respond well to initial platinum-based chemotherapy. However, within a year, many patients experience disease recurrence with a platinum resistant phenotype that responds poorly to second line chemotherapies. As a result, new strategies to address platinum resistant ovarian cancer (PROC) are needed.

Co-delivery of paclitaxel and cisplatin with biocompatible PLGA-PEG nanoparticles enhances chemoradiotherapy in non-small cell lung cancer models.

Chemoradiotherapy (CRT) with paclitaxel (PTX) and cisplatin (CP) is part of the standard of care for patients with locally advanced non-small cell lung cancer (NSCLC). Despite the high treatment intensity, many patients still develop local recurrence after treatment. Thus, there is a strong need to further improve CRT for lung cancer.

Simultaneous measurement of macro- and microvascular blood flow and oxygen saturation for quantification of muscle oxygen consumption.

Purpose: To investigate the relationship between blood flow and oxygen consumption in skeletal muscle, a technique called "Velocity and Perfusion, Intravascular Venous Oxygen saturation and T2*" (vPIVOT) is presented. vPIVOT allows the quantification of feeding artery blood flow velocity, perfusion, draining vein oxygen saturation, and muscle T2*, all at 4-s temporal resolution. Together, the measurement of blood flow and oxygen extraction can yield muscle oxygen consumption ( V˙O2) via the Fick principle.

High-speed whole-brain oximetry by golden-angle radial MRI.

Purpose: To determine whole-brain cerebral metabolic rate of oxygen (CMRO ), an improved imaging approach, based on radial encoding, termed radial OxFlow (rOxFlow), was developed to simultaneously quantify draining vein venous oxygen saturation (SvO ) and total cerebral blood flow (tCBF).

Methods: To evaluate the efficiency and precision of the rOxFlow sequence, 10 subjects were studied during a paradigm of repeated breath-holds with both rOxFlow and Cartesian OxFlow (cOxFlow) sequences. CMRO was calculated at baseline from OxFlow-measured data assuming an arterial O saturation of 97%, and the SvO and tCBF breath-hold responses were quantified.

Nanoparticle delivery of chemotherapy combination regimen improves the therapeutic efficacy in mouse models of lung cancer.

The combination chemotherapy regimen of cisplatin (CP) and docetaxel (DTX) is effective against a variety of cancers. However, combination therapies present unique challenges that can complicate clinical application, such as increases in toxicity and imprecise exposure of tumors to specific drug ratios that can produce treatment resistance. Drug co-encapsulation within a single nanoparticle (NP) formulation can overcome these challenges and further improve combinations' therapeutic index.

Phototriggered Secretion of Membrane Compartmentalized Bioactive Agents.

A strategy for the light-activated release of bioactive compounds (BODIPY, colchicine, paclitaxel, and methotrexate) from membrane-enclosed depots is described. We have found that membrane-permeable bioagents can be rendered membrane impermeable by covalent attachment to cobalamin (Cbl) through a photocleavable linker. These Cbl-bioagent conjugates are imprisoned within lipid-enclosed compartments in the dark, as exemplified by their retention in the interior of erythrocytes.

Calibrated bold fMRI with an optimized ASL-BOLD dual-acquisition sequence.

Calibrated fMRI techniques estimate task-induced changes in the cerebral metabolic rate of oxygen (CMRO) based on simultaneous measurements of cerebral blood flow (CBF) and blood-oxygen-level-dependent (BOLD) signal changes evoked by stimulation. To determine the calibration factor M (corresponding to the maximum possible BOLD signal increase), BOLD signal and CBF are measured in response to a gas breathing challenge (usually CO or O). Here we describe an ASL dual-acquisition sequence that combines a background-suppressed 3D-GRASE readout with 2D multi-slice EPI.

MRI-based methods for quantification of the cerebral metabolic rate of oxygen.

The brain depends almost entirely on oxidative metabolism to meet its significant energy requirements. As such, the cerebral metabolic rate of oxygen (CMRO2) represents a key measure of brain function. Quantification of CMRO2 has helped elucidate brain functional physiology and holds potential as a clinical tool for evaluating neurological disorders including stroke, brain tumors, Alzheimer's disease, and obstructive sleep apnea.

Measurement of skeletal muscle perfusion dynamics with pseudo-continuous arterial spin labeling (pCASL): Assessment of relative labeling efficiency at rest and during hyperemia, and comparison to pulsed arterial spin labeling (PASL).

Purpose: To compare calf skeletal muscle perfusion measured with pulsed arterial spin labeling (PASL) and pseudo-continuous arterial spin labeling (pCASL) methods, and to assess the variability of pCASL labeling efficiency in the popliteal artery throughout an ischemia-reperfusion paradigm.

Materials And Methods: At 3T, relative pCASL labeling efficiency was experimentally assessed in five subjects by measuring the signal intensity of blood in the popliteal artery just distal to the labeling plane immediately following pCASL labeling or control preparation pulses, or without any preparation pulses throughout separate ischemia-reperfusion paradigms. The relative label and control efficiencies were determined during baseline, hyperemia, and recovery.

Susceptibility-based time-resolved whole-organ and regional tissue oximetry.

The magnetism of hemoglobin - being paramagnetic in its deoxy and diamagnetic in its oxy state - offers unique opportunities to probe oxygen metabolism in blood and tissues. The magnetic susceptibility χ of blood scales linearly with blood oxygen saturation, which can be obtained by measuring the magnetic field ΔB of the intravascular MR signal relative to tissue. In contrast to χ, the induced field ΔB is non-local.

Fluorophore Assisted Photolysis of Thiolato-Cob(III)alamins.

Cobalamins are known to react with thiols to yield stable β-axial Co(III)-S bonded thiolato-cobalamin complexes. However, in stark contrast to the Co-C bond in alkylcobalamins, the photolability of the Co-S bond in thiolato-cobalamins remains undetermined. We have investigated the photolysis of N-acetylcysteinyl cob(III)alamin at several wavelengths within the ultraviolet and visible spectrum.

Cerebral metabolic rate of oxygen in obstructive sleep apnea at rest and in response to breath-hold challenge.

Obstructive sleep apnea (OSA) is associated with extensive neurologic comorbidities. It is hypothesized that the repeated nocturnal apneas experienced in patients with OSA may inhibit the normal apneic response, resulting in hypoxic brain injury and subsequent neurologic dysfunction. In this study, we applied the recently developedOxFlowMRI method for rapid quantification of cerebral metabolic rate of oxygen (CMRO2) during a volitional apnea paradigm.

Method for rapid MRI quantification of global cerebral metabolic rate of oxygen.

A recently reported quantitative magnetic resonance imaging (MRI) method denoted OxFlow has been shown to be able to quantify whole-brain cerebral metabolic rate of oxygen (CMRO2) by simultaneously measuring oxygen saturation (SvO2) in the superior sagittal sinus and cerebral blood flow (CBF) in the arteries feeding the brain in 30 seconds, which is adequate for measurement at baseline but not necessarily in response to neuronal activation. Here, we present an accelerated version of the method (referred to as F-OxFlow) that quantifies CMRO2 in 8 seconds scan time under full retention of the parent method's capabilities and compared it with its predecessor at baseline in 10 healthy subjects. Results indicate excellent agreement between both sequences, with mean bias of 2.

Cerebrovascular reactivity measured with arterial spin labeling and blood oxygen level dependent techniques.

Purpose: To compare cerebrovascular reactivity (CVR) quantified with pseudo-continuous arterial spin labeling (pCASL) and blood oxygen level dependent (BOLD) fMRI techniques.

Materials And Methods: Sixteen healthy volunteers (age: 37.8±14.

B(12)-mediated, long wavelength photopolymerization of hydrogels.

Medical hydrogel applications have expanded rapidly over the past decade. Implantation in patients by noninvasive injection is preferred, but this requires hydrogel solidification from a low viscosity solution to occur in vivo via an applied stimuli. Transdermal photo-cross-linking of acrylated biopolymers with photoinitiators and lights offers a mild, spatiotemporally controlled solidification trigger.

Rapid T2- and susceptometry-based CMRO2 quantification with interleaved TRUST (iTRUST).

Susceptometry-based oximetry (SBO) and T2-relaxation-under-spin-tagging (TRUST) are two promising methods for quantifying the cerebral metabolic rate of oxygen (CMRO2), a critical parameter of brain function. We present a combined method, interleaved TRUST (iTRUST), which achieves rapid, simultaneous quantification of both susceptometry- and T2-based CMRO2 via insertion of a flow-encoded, dual-echo gradient-recalled echo (OxFlow) module within the T1 recovery portion of the TRUST sequence. In addition to allowing direct comparison between SBO- and TRUST-derived venous oxygen saturation (Yv) values, iTRUST substantially improves TRUST temporal resolution for CMRO2 quantification and obviates the need for a separate blood flow measurement following TRUST acquisition.

Cell-mediated assembly of phototherapeutics.

Light-activatable drugs offer the promise of controlled release with exquisite temporal and spatial resolution. However, light-sensitive prodrugs are typically converted to their active forms using short-wavelength irradiation, which displays poor tissue penetrance. We report herein erythrocyte-mediated assembly of long-wavelength-sensitive phototherapeutics.

Comparison of MRI methods for measuring whole-brain venous oxygen saturation.

Purpose: In this work, we compare susceptometry-based oximetry (SBO) and two T2 -based methods for estimating resting baseline SvO2 in the superior sagittal sinus (SSS).

Methods: SBO is a field-mapping technique whereas in T2 -based methods the intravascular blood signal is isolated either with velocity-encoded projections [projection-based T2 (PT2 )] or a tag-control scheme [T2 -relaxation under spin tagging (TRUST)] after T2 -preparation. The measurements were performed on twelve healthy subjects (mean age = 33 ± 6 years) at 3 Tesla field strength.

Time-resolved MRI oximetry for quantifying CMRO(2) and vascular reactivity.

This brief review of magnetic resonance susceptometry summarizes the methods conceived in the authors' laboratory during the past several years. This article shows how venous oxygen saturation is quantified in large draining veins by field mapping and how this information, in concert with simultaneous measurement of cerebral blood flow, yields cerebral metabolic rate of oxygen, the brain's rate of oxygen consumption. The accuracy of this model-based approach in which the blood vessel is approximated as a long, straight cylinder, for which an analytical solution for the induced field exists, is discussed.

Tunable visible and near-IR photoactivation of light-responsive compounds by using fluorophores as light-capturing antennas.

Although the corrin ring of vitamin B12 is unable to efficiently absorb light beyond 550 nm, it is shown that commercially available fluorophores can be used as antennas to capture long-wavelength light to promote scission of the Co-C bond at wavelengths up to 800 nm. The ability to control the molecular properties of bioactive species with long visible and near-IR light has implications for drug delivery, nanotechnology, and the spatiotemporal control of cellular behavior.