Surface dielectric resonator for in vivo EPR measurements.

This research report describes a novel surface dielectric resonator (SDR) with a flexible connector for in vivo electron paramagnetic resonance (EPR) spectroscopy. Contrary to the conventional cavity or surface loop-gap resonators, the newly developed SDR is constructed from a ceramic dielectric material, and it is tuned to operate at the L-band frequency band (1.15 GHz) in continuous-wave mode.

Feasibility study of multimodal imaging for redox status and glucose metabolism in tumor.

Understanding the tumor redox status is important for efficient cancer treatment. Here, we noninvasively detected changes in the redox environment of tumors before and after cancer treatment in the same individuals using a novel compact and portable electron paramagnetic resonance imaging (EPRI) device and compared the results with glycolytic information obtained through autoradiography using 2-deoxy-2-[F]fluoro-d-glucose ([F]FDG). Human colon cancer HCT116 xenografts were used in the mice.

Pulse and CW EPR Oximetry Using Oxychip in Gemcitabine-Treated Murine Pancreatic Tumors.

Purpose: The goal of this work was to compare pO measured using both continuous wave (CW) and pulse electron paramagnetic resonance (EPR) spectroscopy. The Oxychip particle spin probe enabled longitudinal monitoring of pO in murine pancreatic tumor treated with gemcitabine during the course of therapy.

Procedures: Pancreatic PanO2 tumors were growing in the syngeneic mice, in the leg.

Oxygen therapeutic window induced by myo-inositol trispyrophosphate (ITPP)-Local pO2 study in murine tumors.

Hypoxia, an inevitable feature of locally advanced solid tumors, has been known as an adverse prognostic factor, a driver of an aggressive phenotype, and an unfavorable factor in therapies. Myo-inositol trispyrophosphate (ITPP) is a hemoglobin modifier known to both increase O2 release and normalize microvasculature. Our goal was to measure the tumor oxygen partial pressure dynamic changes and timing of the therapeutic window after ITPP systemic administration.

Evaluation of a Refined Implantable Resonator for Deep-Tissue EPR Oximetry in the Clinic.

Objectives: (1) Summarize revisions made to the implantable resonator (IR) design and results of testing to characterize biocompatibility;(2) Demonstrate safety of implantation and feasibility of deep tissue oxygenation measurement using electron paramagnetic resonance (EPR) oximetry.

Study Design: In vitro testing of the revised IR and in vivo implantation in rabbit brain and leg tissues.

Methods: Revised IRs were fabricated with 1-4 OxyChips with a thin wire encapsulated with two biocompatible coatings.

OxyChip embedded with radio-opaque gold nanoparticles for anatomic registration and oximetry in tissues.

Purpose: Electron paramagnetic resonance oximetry using the OxyChip as an implantable oxygen sensor can directly and repeatedly measure tissue oxygen levels. A phase I, first-in-human clinical study has established the safety and feasibility of using OxyChip for reliable and repeated measurements of oxygen levels in a variety of tumors and treatment regimens. A limitation in these studies is the inability to easily locate and identify the implanted probes in the tissue, particularly in the long term, thus limiting spatial/anatomical registration of the implant for proper interpretation of the oxygen data.

First-In-Human Study in Cancer Patients Establishing the Feasibility of Oxygen Measurements in Tumors Using Electron Paramagnetic Resonance With the OxyChip.

Objective: The overall objective of this clinical study was to validate an implantable oxygen sensor, called the 'OxyChip', as a clinically feasible technology that would allow individualized tumor-oxygen assessments in cancer patients prior to and during hypoxia-modification interventions such as hyperoxygen breathing.

Methods: Patients with any solid tumor at ≤3-cm depth from the skin-surface scheduled to undergo surgical resection (with or without neoadjuvant therapy) were considered eligible for the study. The OxyChip was implanted in the tumor and subsequently removed during standard-of-care surgery.

Estimation of pO distribution in EPR oximetry.

Electron paramagnetic resonance (EPR) oximetry, using oxygen-sensing implant such as OxyChip, is capable of measuring oxygen concentration in vivo - a critical tissue information required for successful medical treatment such as cancer, wound healing and diabetes. Typically, EPR oximetry produces one value of the oxygen concentration, expressed as pO at the site of implant. However, it is well recognized that in vivo one deals with a distribution of oxygen concentration and therefore reporting just one number is not representative_a long-standing critique of EPR oximetry.

Selective Induction of Cellular Toxicity and Anti-tumor Efficacy by N-Methylpiperazinyl Diarylidenylpiperidone and its Pro-nitroxide Conjugate through ROS-mediated Mitochondrial Dysfunction and G2/M Cell-cycle Arrest in Human Pancreatic Cancer.

Pancreatic adenocarcinoma is an aggressive cancer with poor clinical prognosis and limited therapeutic options. There is a significant lack of effective, safe, and targeted therapies for successful treatment of pancreatic cancer. In this report, we describe the anticancer efficacy of two novel compounds, N-methylpiperazinyl diarylidenylpiperidone (L-2663) and its pro-nitroxide conjugate (HO-4589) evaluated on human pancreatic adenocarcinoma (AsPC-1) cell line and xenograft tumor in mice.

Estimation of pO histogram from a composite EPR Spectrum of multiple random implants.

Electron paramagnetic resonance (EPR) spectroscopy using oxygen-sensing implants can provide reliable and repeated measurements of the partial pressure of oxygen (pO) over a period of months or longer; however, it does not provide accurate information about the distribution of tissue oxygenation. While EPR imaging has the capability to provide spatially resolved oxygen data, it is time-consuming and not optimized for discrete number of implants. Previous reports suggest multi-site algorithms, which would require either the implants to be aligned in a certain way so as to deconvolve them using a linear magnetic field gradient or sparse imaging of the implants from a small number of 3D projections.

Implantable microchip containing oxygen-sensing paramagnetic crystals for long-term, repeated, and multisite in vivo oximetry.

EPR oximetry is established as a viable method for measuring the tissue oxygen level (partial pressure of oxygen, pO) in animal models; however, it has not yet been established for measurements in humans. EPR oximetry requires an oxygen-sensing paramagnetic probe (molecular or particulate) to be placed at the site/organ of measurement, which may pose logistical and safety concerns, including invasiveness of the probe-placement procedure as well as lack of temporal stability and sensitivity for long-term (repeated) measurements, and possible toxicity in the short- and long-term. In the past, we have developed an implantable oxygen-sensing probe, called OxyChip, which we have successfully established for oximetry in pre-clinical animal models (Hou et al.

Diarylidenylpiperidones, H-4073 and HO-3867, Induce G2/M Cell-Cycle Arrest, Apoptosis and Inhibit STAT3 Phosphorylation in Human Pancreatic Cancer Cells.

Pancreatic cancer has a 5-year survival rate below 10% and the treatment options are limited. Signal transducer and activator of transcription (STAT3) is a constitutively expressed protein in human pancreatic cancers and is associated with their poor prognosis. Targeting of STAT3 signaling using novel therapeutic agents is a potential strategy for pancreatic cancer treatment.

Application of SPOT chip for transcutaneous oximetry.

This response is provided to address the questions raised in the letter to the editor by Henni et al. on our manuscript (Kmiec et al. Magn Reson Med 2019;81:781-794) describing the development of a new method for transcutaneous oxygen measurement in humans based on electron paramagnetic resonance (EPR) technology using SPOT chip.

Transcutaneous oxygen measurement in humans using a paramagnetic skin adhesive film.

Purpose: Transcutaneous oxygen tension (TcpO ) provides information about blood perfusion in the tissue immediately below the skin. These data are valuable in assessing wound healing problems, diagnosing peripheral vascular/arterial insufficiency, and predicting disease progression or the response to therapy. Currently, TcpO is primarily measured using electrochemical skin sensors, which consume oxygen and are prone to calibration errors.

Development of the Implantable Resonator System for Clinical EPR Oximetry.

Hypoxic tumors are more resistant to radiotherapy and chemotherapy, which decreases the efficacy of these common forms of treatment. We have been developing implantable paramagnetic particulates to measure oxygen in vivo using electron paramagnetic resonance. Once implanted, oxygen can be measured repeatedly and non-invasively in superficial tissues (<3 cm deep), using an electron paramagnetic resonance spectrometer and an external surface-loop resonator.

Surface Dielectric Resonators for X-band EPR Spectroscopy.

A new resonator for X-band electron paramagnetic resonance (EPR) spectroscopy, which utilizes the unique resonance properties of dielectric substrates, has been developed using a single crystal of titanium dioxide. As a result of the dielectric properties of the crystal(s) chosen, this novel resonator provides the ability to make in vivo EPR spectroscopy surface measurements in the presence of lossy tissues at X-band frequencies (up to 10 GHz). A double-loop coupling device is used to transmit and receive microwave power to/from the resonator.

Dielectric-Backed Aperture Resonators for X-Band in vivo EPR Nail Dosimetry.

A new resonator for X-band in vivo EPR nail dosimetry, the dielectric-backed aperture resonator (DAR), is developed based on rectangular TE geometry. This novel geometry for surface spectroscopy improves at least a factor of 20 compared to a traditional non-backed aperture resonator. Such an increase in EPR sensitivity is achieved by using a non-resonant dielectric slab, placed on the aperture inside the cavity.

Tooth Retrospective Dosimetry Using Electron Paramagnetic Resonance: Influence of Irradiated Dental Composites.

In the aftermath of a major radiological accident, the medical management of overexposed individuals will rely on the determination of the dose of ionizing radiations absorbed by the victims. Because people in the general population do not possess conventional dosimeters, after the fact dose reconstruction methods are needed. Free radicals are induced by radiations in the tooth enamel of victims, in direct proportion to dose, and can be quantified using Electron Paramagnetic Resonance (EPR) spectrometry, a technique that was demonstrated to be very appropriate for mass triage.

Imaging tooth enamel using zero echo time (ZTE) magnetic resonance imaging.

In an event where many thousands of people may have been exposed to levels of radiation that are sufficient to cause the acute radiation syndrome, we need technology that can estimate the absorbed dose on an individual basis for triage and meaningful medical decision making. Such dose estimates may be achieved using in vivo electron paramagnetic resonance (EPR) tooth biodosimetry, which measures the number of persistent free radicals that are generated in tooth enamel following irradiation. However, the accuracy of dose estimates may be impacted by individual variations in teeth, especially the amount and distribution of enamel in the inhomogeneous sensitive volume of the resonator used to detect the radicals.

The view from the trenches: part 2-technical considerations for EPR screening.

There is growing awareness of the need for methodologies that can be used retrospectively to provide the biodosimetry needed to carry out screening and triage immediately after an event in which large numbers of people have potentially received clinically significant doses of ionizing radiation. The general approach to developing such methodologies has been a technology centric one, often ignoring the system integrations considerations that are key to their effective use. In this study an integrative approach for the evaluation and development of a physical biodosimetry technology was applied based on in vivo electron paramagnetic resonance (EPR) dosimetry.