Composite spin probes with adjustable oxygen sensitivity for pulse electron paramagnetic resonance imaging.

Purpose: Solid crystalline spin probes, such as lithium phthalocyanine (LiPc) and lithium octa-n-butoxynaphthalocyanine (LiNc-BuO), allow repeated oxygen measurement using electron paramagnetic resonance (EPR). Due to their short relaxation times, their use for pulse EPR oxygen imaging is limited. In this study, we developed and tested a new class of solid composite spin probes that modified the relaxation rates R and R of LiPc or LiNc-BuO probes, which allowed pO measurements in the full dynamic (0-760 torr) range.

A fully linearized ADMM algorithm for optimization based image reconstruction.

Background And Objective: Optimization based image reconstruction algorithm is an advanced algorithm in medical imaging. However, the corresponding solving algorithm is challenging because the model is usually large-scale and non-smooth. This work aims to devise a simple and convergent solver for optimization model.

In Vivo Mouse Abdominal Oxygen Imaging And Assessment of Subcutaneously Implanted Beta Cell Replacement Devices.

Purpose: Type 1 diabetes (T1D) is an autoimmune disease that leads to the loss of insulin-producing pancreatic beta cells. Beta cell replacement devices or bioartificial pancreas (BAP) have shown promise in curing T1D and providing long-term insulin independence without the need for immunosuppressants. Hypoxia in BAP devices damages cells and imposes limitations on device dimensions.

Validation of the design of a high-sensitivity and high-resolution PET system for a preclinical PET/EPR hybrid scanner.

We report the development of a high-sensitivity and high-resolution PET subsystem for a next-generation preclinical PET/EPR hybrid scanner for investigating and improving hypoxia imaging with PET. The PET subsystem consists of 14 detector modules (DM) installed within a cylindrical supporting frame whose outer and inner diameters are 115mm and 60mm, respectively. Each DM contains eight detector units (DU) in a row and each DU is made of a 12×12 array of 1×1×10mm LYSO crystals (with a 1.

Directional TV algorithm for image reconstruction from sparse-view projections in EPR imaging.

Electron paramagnetic resonance (EPR) imaging is an advanced in vivo oxygen imaging modality. The main drawback of EPR imaging is the long scanning time. Sparse-view projections collection is an effective fast scanning pattern.

Directional TV algorithm for fast EPR imaging.

Precise radiation guided by oxygen images has demonstrated superiority over the traditional radiation methods. Electron paramagnetic resonance (EPR) imaging has proven to be the most advanced oxygen imaging modality. However, the main drawback of EPR imaging is the long scan time.

Assessment of blood-brain barrier leakage and brain oxygenation in Connexin-32 knockout mice with systemic neuroinflammation using pulse electron paramagnetic resonance imaging techniques.

Purpose: The determination of blood-brain barrier (BBB) integrity and partial pressure of oxygen (pO) in the brain is of substantial interest in several neurological applications. This study aimed to assess the feasibility of using trityl OX071-based pulse electron paramagnetic resonance imaging (pEPRI) to provide a quantitative estimate of BBB integrity and pO maps in mouse brains as a function of neuroinflammatory disease progression.

Methods: Five Connexin-32 (Cx32)-knockout (KO) mice were injected with lipopolysaccharide to induce neuroinflammation for imaging.

Corrigendum: Absolute oxygen-guided radiation therapy improves tumor control in three preclinical tumor models.

[This corrects the article DOI: 10.3389/fmed.2023.

Inflammation-induced subcutaneous neovascularization for the long-term survival of encapsulated islets without immunosuppression.

Cellular therapies for type-1 diabetes can leverage cell encapsulation to dispense with immunosuppression. However, encapsulated islet cells do not survive long, particularly when implanted in poorly vascularized subcutaneous sites. Here we show that the induction of neovascularization via temporary controlled inflammation through the implantation of a nylon catheter can be used to create a subcutaneous cavity that supports the transplantation and optimal function of a geometrically matching islet-encapsulation device consisting of a twisted nylon surgical thread coated with an islet-seeded alginate hydrogel.

HIF-stabilizing biomaterials: from hypoxia-mimicking to hypoxia-inducing.

Recent advances in our understanding of hypoxia and hypoxia-mediated mechanisms shed light on the critical implications of the hypoxic stress on cellular behavior. However, tools emulating hypoxic conditions (, low oxygen tensions) for research are limited and often suffer from major shortcomings, such as lack of reliability and off-target effects, and they usually fail to recapitulate the complexity of the tissue microenvironment. Fortunately, the field of biomaterials is constantly evolving and has a central role to play in the development of new technologies for conducting hypoxia-related research in several aspects of biomedical research, including tissue engineering, cancer modeling, and modern drug screening.

A Preclinical Positron Emission Tomography (PET) and Electron-Paramagnetic-Resonance-Imaging (EPRI) Hybrid System: PET Detector Module.

We report the design and experimental validation of a compact positron emission tomography (PET) detector module (DM) intended for building a preclinical PET and electron-paramagnetic-resonance-imaging hybrid system that supports sub-millimeter image resolution and high-sensitivity, whole-body animal imaging. The DM is eight detector units (DU) in a row. Each DU contains 12×12 lutetium-yttrium oxyorthosilicate (LYSO) crystals having a 1.

SOX71, A Biocompatible Succinyl Derivative of the Triarylmethyl Radical OX071 for In Vivo Quantitative Oxygen Mapping Using Electron Paramagnetic Resonance.

Purpose: This study aimed to develop a biocompatible oximetric electron paramagnetic resonance (EPR) spin probe with reduced self-relaxation, and sensitivity to oxygen for a higher signal-to-noise ratio and longer relaxation times at high oxygen concentration, compared to the reference spin probe OX071.

Procedures: SOX71 was synthesized by succinylation of the twelve alcohol groups of OX071 spin probe and characterized by EPR at X-Band (9.5 GHz) and at low field (720 MHz).

Absolute oxygen-guided radiation therapy improves tumor control in three preclinical tumor models.

Background: Clinical attempts to find benefit from specifically targeting and boosting resistant hypoxic tumor subvolumes have been promising but inconclusive. While a first preclinical murine tumor type showed significant improved control with hypoxic tumor boosts, a more thorough investigation of efficacy from boosting hypoxic subvolumes defined by electron paramagnetic resonance oxygen imaging (EPROI) is necessary. The present study confirms improved hypoxic tumor control results in three different tumor types using a clonogenic assay and explores potential confounding experimental conditions.

Toward a Nanoencapsulated EPR Imaging Agent for Clinical Use.

Purpose: Progress toward developing a novel radiocontrast agent for determining pO in tumors in a clinical setting is described. The imaging agent is designed for use with electron paramagnetic resonance imaging (EPRI), in which the collision of a paramagnetic probe molecule with molecular oxygen causes a spectroscopic change which can be calibrated to give the real oxygen concentration in the tumor tissue.

Procedures: The imaging agent is based on a nanoscaffold of aluminum hydroxide (boehmite) with sizes from 100 to 200 nm, paramagnetic probe molecule, and encapsulation with a gas permeable, thin (10-20 nm) polymer layer to separate the imaging agent and body environment while still allowing O to interact with the paramagnetic probe.

In vitro oxygen imaging of acellular and cell-loaded beta cell replacement devices.

Type 1 diabetes (T1D) is an autoimmune disease that leads to the loss of insulin-producing beta cells. Bioartificial pancreas (BAP) or beta cell replacement strategies have shown promise in curing T1D and providing long-term insulin independence. Hypoxia (low oxygen concentration) that may occur in the BAP devices due to cell oxygen consumption at the early stages after implantation damages the cells, in addition to imposing limitations to device dimensions when translating promising results from rodents to humans.

Oxygen Imaging of a Rabbit Tumor Using a Human-Sized Pulse Electron Paramagnetic Resonance Imager.

Purpose: Spatial heterogeneity in tumor hypoxia is one of the most important factors regulating tumor growth, development, aggressiveness, metastasis, and affecting treatment outcome. Most solid tumors are known to have hypoxia or low oxygen levels (pO ≤10 torr). Electron paramagnetic resonance oxygen imaging (EPROI) is an emerging oxygen mapping technology.

A Simple but Universal Fully Linearized ADMM Algorithm for Optimization Based Image Reconstruction.

Background And Objective: Optimization based image reconstruction algorithm is an advanced algorithm in medical imaging. However, the corresponding solving algorithm is challenging because the optimization model is usually large-scale and non-smooth. This work aims to devise a simple but universal solver for optimization models.

4D-image reconstruction directly from limited-angular-range data in continuous-wave electron paramagnetic resonance imaging.

Objective: We investigate and develop optimization-based algorithms for accurate reconstruction of four-dimensional (4D)-spectral-spatial (SS) images directly from data collected over limited angular ranges (LARs) in continuous-wave (CW) electron paramagnetic resonance imaging (EPRI).

Methods: Basing on a discrete-to-discrete data model devised in CW EPRI employing the Zeeman-modulation (ZM) scheme for data acquisition, we first formulate the image reconstruction problem as a convex, constrained optimization program that includes a data fidelity term and also constraints on the individual directional total variations (DTVs) of the 4D-SS image. Subsequently, we develop a primal-dual-based DTV algorithm, simply referred to as the DTV algorithm, to solve the constrained optimization program for achieving image reconstruction from data collected in LAR scans in CW-ZM EPRI.

Direct Measurement and Imaging of Redox Status with Electron Paramagnetic Resonance.

Fundamental to the application of tissue redox status to human health is the quantification and localization of tissue redox abnormalities and oxidative stress and their correlation with the severity and local extent of disease to inform therapy. The centrality of the low-molecular-weight thiol, glutathione, in physiological redox balance has long been appreciated, but direct measurement of tissue thiol status has not been possible hitherto. Recent advances in instrumentation and molecular probes suggest the feasibility of real-time redox assessment in humans.

An iterative reconstruction algorithm without system matrix for EPR imaging.

Electron paramagnetic resonance (EPR) imaging is an advanced oxygen imaging modality for oxygen-image guided radiation. The iterative reconstruction algorithm is the research hot-point in image reconstruction for EPR imaging (EPRI) for this type of algorithm may incorporate image-prior information to construct advanced optimization model to achieve accurate reconstruction from sparse-view projections and/or noisy projections. However, the system matrix in the iterative algorithm needs complicated calculation and needs huge memory-space if it is stored in memory.

The optimal F-fluoromisonidazole PET threshold to define tumor hypoxia in preclinical squamous cell carcinomas using pO electron paramagnetic resonance imaging as reference truth.

Purpose: To identify the optimal threshold in F-fluoromisonidazole (FMISO) PET images to accurately locate tumor hypoxia by using electron paramagnetic resonance imaging (pO EPRI) as ground truth for hypoxia, defined by pO [Formula: see text] 10 mmHg.

Methods: Tumor hypoxia images in mouse models of SCCVII squamous cell carcinoma (n = 16) were acquired in a hybrid PET/EPRI imaging system 2 h post-injection of FMISO. T2-weighted MRI was used to delineate tumor and muscle tissue.

Partial Oxygen Pressure Assessment in Subcutaneous and Intraperitoneal Sites Using Imaging of Solid Oxygen Probe.

The purpose of this study was to assess the natural partial oxygen pressure (pO) of subcutaneous (SC) and intraperitoneal (IP) sites in mice to determine their relative suitability as sites for placement of implants. The pO measurements were performed using oxygen imaging of solid probes using lithium phthalocyanine (LiPc) as the oxygen sensitive material. LiPc is a water-insoluble crystalline probe whose spin-lattice and spin-spin relaxation rates ( and ) are sensitive to the local oxygen concentration.

Amniotic growth factors enhanced human pre-adipocyte cell viability and differentiation under hypoxia.

One of the major drawbacks associated with autologous fat grafting is unpredictable graft retention. Various efforts to improve the survivability of these cells have been explored, but these methods are time-consuming, complex, and demand significant technical skill. In our study, we examine the use of cryopreserved amniotic membrane as a source of exogenous growth factors to improve adipocyte survivability under normal and hypoxic conditions.