Huagang Hou

Huagang Hou
Geisel School of Medicine at Dartmouth | DMS · Department of Radiology

MD.

About

81
Publications
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2,229
Citations
Citations since 2016
16 Research Items
1092 Citations
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2016201720182019202020212022050100150200
2016201720182019202020212022050100150200
2016201720182019202020212022050100150200

Publications

Publications (81)
Article
Full-text available
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 so...
Article
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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...
Article
Background: The goal of red blood cell transfusion is to improve tissue oxygenation. Assessment of red blood cell quality and individualised therapeutic needs can be optimised using direct oxygen (O2) measurements to guide treatment. Electron paramagnetic resonance oximetry is capable of accurate, repeatable and minimally invasive measurements of...
Article
Objectives/Hypothesis To determine if electron paramagnetic resonance (EPR) oximetry is a viable technology to aid in flap monitoring. Study Design Prospective cohort. Methods This was a cohort study assessing accuracy and speed of EPR oximetry in detecting ischemia of a saphenous artery–based flap in a rat model, using transcutaneous oximetry as...
Article
Purpose Transcutaneous oxygen tension (TcpO2) 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, TcpO2 is primarily measured u...
Article
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Tissue oxygenation is a critical parameter in various pathophysiological situations including cardiovascular disease and cancer. Hypoxia can significantly influence the prognosis of solid malignancies and the efficacy of their treatment by radiation or chemotherapy. Electron paramagnetic resonance (EPR) oximetry is a reliable method for repeatedly...
Article
Full-text available
Cerebral tissue oxygenation (oxygen tension, pO2) is a critical parameter that is closely linked to brain metabolism, function, and pathophysiology. In this work, we have used electron paramagnetic resonance oximetry with a deep-tissue multi-site oxygen-sensing probe, called implantable resonator, to monitor temporal changes in cerebral pO2 simulta...
Article
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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 tissue...
Chapter
The objective of this work was to establish a novel and robust technology, based on electron paramagnetic resonance (EPR) oximetry, as a practical tool for measurement of tumor oxygen. Previously, we have reported on the development of oxygen-sensing paramagnetic crystals (LiNc-BuO) encapsulated in a biocompatible polymer, called OxyChip. In this r...
Article
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Gemcitabine irreversibly inhibits ribonucleotide reductase and induces S phase arrest but whether this occurs in tumors in mice or patients has not been established. Tumor cells in culture were incubated with gemcitabine for 6 h to approximate the administration schedule in a patient. Concentrations that induced persistent S phase arrest thereafter...
Article
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The effect of hyperoxygenation with carbogen (95% O 2 + 5% CO 2 ) and 100% oxygen inhalation on partial pressure of oxygen (pO 2 ) of radiation-induced fibrosarcoma (RIF-1) tumor was investigated. RIF-1 tumors were innoculated in C3H mice, and aggregates of oximetry probe, lithium phthalocyanine (LiPc), was implanted in each tumor. A baseline tumor...
Chapter
A number of studies have reported benefits associated with the application of hyperbaric oxygen treatment (HBO) delivered immediately prior to radiation therapy. While these studies provide evidence that pre-treatment with HBO may be beneficial, no measurements of intratumoral pO2 were carried out and they do not directly link the apparent benefits...
Chapter
We have incorporated LiNc-BuO, an oxygen-sensing paramagnetic material, in polydimethylsiloxane (PDMS), which is an oxygen-permeable, biocompatible, and stable polymer. We fabricated implantable and retrievable oxygen-sensing chips (40 % LiNc-BuO in PDMS) using a 20-G Teflon tubing to mold the chips into variable shapes and sizes for in vivo studie...
Chapter
The first systematic multi-center study of the clinical use of EPR oximetry has begun, with funding as a PPG from the NCI. Using particulate oxygen sensitive EPR, materials in three complementary forms (India Ink, “OxyChips”, and implantable resonators) the clinical value of the technique will be evaluated. The aims include using repeated measureme...
Chapter
Low level of oxygen (hypoxia) is a critical factor that defines the pathological consequence of several pathophysiologies, particularly ischemia, that usually occur following the blockage of a blood vessel in vital organs, such as brain and heart, or abnormalities in the microvasculature, such as peripheral vascular disease. Therefore, methods that...
Article
In the working heart coronary blood flow is linked to the production of metabolites, which modulate tone of smooth muscle in a redox-dependent manner. Voltage-gated potassium channels, which play a role in controlling membrane potential in vascular smooth muscle, have certain members that are redox sensitive. In the working heart coronary blood flo...
Article
Hypoxia is a critical hallmark of glioma, and significantly compromises treatment efficacy. Unfortunately, techniques for monitoring glioma pO2 to facilitate translational research are lacking. Furthermore, poor prognoses of patients with malignant glioma, in particular glioblastoma multiforme, warrant effective strategies that can inhibit hypoxia...
Article
Purpose Electron paramagnetic resonance (EPR) oximetry using variable length multi-probe implantable resonator (IR), was used to investigate the temporal changes in the ischemic and contralateral brain pO2 during stroke in rats. Material and methods The EPR signal to noise ratio (S/N) of the IR with four sensor loops at a depth of up to11 mm were...
Article
The use of electron paramagnetic resonance (EPR) oximetry for oxygen measurements in deep tissues (>1 cm) is challenging due to the limited penetration depth of the microwave energy. To overcome this limitation, implantable resonators, having a small (0.5 mm diameter) sensory loop containing the oxygen-sensing paramagnetic material connected by a p...
Article
A hypoxic microenvironment in solid tumors has been known to cause resistance to standard therapies and to increase the malignant potential of tumors. The utilization of magnetic nanoparticle hyperthermia (mNPH) has shown promise in improving therapeutic outcome by (1) killing of hypoxic tumor cells directly and (2) increasing tumor oxygenation and...
Article
The feasibility of EPR oximetry using a single-probe implantable oxygen sensor (ImOS) was tested for repeated measurement of pO2 in skeletal muscle and ectopic 9L tumors in rats. The ImOS (50 mm length) were constructed using nickel-chromium alloy wires, with lithium phthalocyanine (LiPc, oximetry probe) crystals loaded in the sensor loop and coate...
Article
A lack of strategy to counteract hypoxia (pO2 < 10–15 mmHg) and technique to repeatedly measure tumor pO2 has restricted therapeutic optimization. We report the results obtained with an innovative anti-angiogenic strategy of recurrent low-dose (metronomic) chemotherapy to modulate hypoxia and growth of the Head and Neck tumor xenografts. The FaDu t...
Article
EPR oximetry, which enables reliable, accurate, and repeated measurements of the partial pressure of oxygen in tissues, provides a unique opportunity to investigate the role of oxygen in the pathogenesis and treatment of several diseases including cancer, stroke, and heart failure. Building on significant advances in the in vivo application of EPR...
Article
Electron paramagnetic resonance (EPR) spectroscopy has been well established as a viable technique for measurement of free radicals and oxygen in biological systems, from in vitro cellular systems to in vivo small animal models of disease. However, the use of EPR in human subjects in the clinical setting, although attractive for a variety of import...
Article
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Chk1 inhibitors have emerged as promising anticancer therapeutic agents particularly when combined with antimetabolites such as gemcitabine, cytarabine or hydroxyurea. Here, we address the importance of appropriate drug scheduling when gemcitabine is combined with the Chk1 inhibitor MK-8776, and the mechanisms involved in the schedule dependence. G...
Article
Gemcitabine inhibits ribonucleotide reductase, prevents synthesis of deoxyribonucleotides, and induces arrest of cells in S phase. Subsequent inhibition of Chk1 causes the stalled replication forks to collapse, thereby increasing cell death. We have observed up to 10-fold decrease in the growth-inhibitory concentration (IC50) of gemcitabine upon in...
Article
Tumor hypoxia impedes the outcome of radiotherapy. As the extent of hypoxia in solid tumors varies during the course of radiotherapy, methods that can provide repeated assessment of tumor pO(2) such as EPR oximetry may enhance the efficacy of radiotherapy by scheduling irradiations when the tumors are oxygenated. The repeated measurements of tumor...
Article
Survival of head and neck cancer patients has not improved in several decades despite advances in diagnostic and therapeutic techniques. Tumor hypoxia in head and neck cancers is a critical factor that leads to poor prognosis, resistance to radiation and chemotherapies, and increased metastatic potential. Magnetic nanoparticle hyperthermia (mNPHT)...
Article
Oxygen affects the activity of multiple skeletogenic cells and is involved in many processes that are important for fracture healing. However, the role of oxygen in fracture healing has not been fully studied. Here we systematically examine the effects of oxygen tension on fracture healing and test the ability of hyperoxia to rescue healing defects...
Article
Several techniques currently exist for measuring tissue oxygen; however technical difficulties have limited their usefulness and general application. We report a recently developed electron paramagnetic resonance (EPR) oximetry approach with multiple probe implantable resonators (IRs) that allow repeated measurements of oxygen in tissue at depths o...
Article
Tumor hypoxia plays a vital role in therapeutic resistance. Consequently, measurements of tumor pO(2) could be used to optimize the outcome of oxygen-dependent therapies, such as, chemoradiation. However, the potential optimizations are restricted by the lack of methods to repeatedly and quantitatively assess tumor pO(2) during therapies, particula...
Article
The goal of this study was to determine to what extent mechanical stability affects vascular repair during fracture healing. Stabilized and nonstabilized tibia fractures were created in adult mice. Fracture tissues were collected at multiple time points during early fracture healing. Vasculature in fractured limbs was visualized by immunohistochemi...
Article
The effect of hyperoxygenation with carbogen (95% O(2) + 5% CO(2)) inhalation on RIF-1 tumor pO(2 )and its consequence on growth inhibition with fractionated radiotherapy is reported. The temporal changes in the tumor pO(2) were assessed by in vivo Electron Paramagnetic Resonance (EPR) oximetry in mice breathing 30% O(2) or carbogen and the tumors...
Article
Full-text available
Malignant gliomas are aggressive and angiogenic tumors with high VEGF content. Consequently, approaches such as metronomic chemotherapy, which have an anti-angiogenic effect, are being investigated. However, a lack of an appropriate technique that can facilitate the identification of vascular changes during antiangiogenic treatments has restricted...
Article
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Exposure to high altitude or hypobaric hypoxia results in a series of metabolic, physiologic, and genetic changes that serve to acclimate the brain to hypoxia. Tissue Po(2) (Pto(2)) is a sensitive index of the balance between oxygen delivery and utilization and can be considered to represent the summation of such factors as cerebral blood flow, cap...
Article
Multi-site electron paramagnetic resonance (EPR) oximetry, using multi-probe implantable resonators, was used to measure the partial pressure of oxygen (pO(2)) in the brains of rats following normobaric hyperoxia and mild hypoxia. The cerebral tissue pO(2) was measured simultaneously in the cerebral cortex and striatum in the same rats before, duri...
Article
Tumor hypoxia is a well known therapeutic problem which contributes to radioresistance and aggressive tumor characteristics. Lack of techniques for repeated measurements of tumor oxygenation (pO2, partial pressure of oxygen) has restricted the optimization of hypoxia modifying methods and their efficacious application with radiotherapy. We have inv...
Article
Glioblastomas are aggressive and highly vascularized primary brain tumors with a 5-year survival rate of less than 10%. Approaches targeting tumor vasculature are currently being investigated to achieve therapeutic benefits for this fatal malignancy. However, lack of suitable markers that can be used to monitor therapeutic effects during such treat...
Article
Lack of methods for repeated assessment of tumor pO(2) limits the ability to test and optimize hypoxia-modifying procedures being developed for clinical applications. We report repeated measurements of orthotopic F98 tumor pO(2) and relate this to the effect of carbogen inhalation on tumor growth when combined with hypofractionated radiotherapy. El...
Article
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We sought to reduce tumor hypoxia by topical application of a vasodilator, benzyl nicotinate (BN), and investigated its effect on the growth of tumors irradiated at times when tumor pO(2) increased. EPR oximetry was used to follow the changes in the tissue pO(2) of subcutaneous radiation-induced fibrosarcoma (RIF-1) tumors during topical applicatio...
Article
EPR oximetry using implantable resonators allows measurements at much deeper sites than are possible with surface resonators (> 80 vs. 10 mm) and achieves greater sensitivity at any depth. We report here the development of an improved technique that enables us to obtain the information from multiple sites and at a variety of depths. The measurement...
Article
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Checkpoint inhibitors potentially could be used to enhance cell killing by DNA-targeted therapeutic modalities such as radiotherapy. UCN-01 (7-hydroxystaurosporine) inhibits S and G2 checkpoint arrest in the cells of various malignant cell lines and has been investigated in combination with chemotherapy. However, little is known about its potential...
Article
Tumor hypoxia is a well-known therapeutic problem; however, a lack of methods for repeated measurements of glioma partial pressure of oxygen (pO(2)) limits the ability to optimize the therapeutic approaches. We report the effects of 9.3 Gy of radiation and carbogen inhalation on orthotopic 9L and C6 gliomas and on the contralateral brain pO(2) in r...
Article
To investigate the temporal effects of single or fractionated radiotherapy on subcutaneous RIF-1 tumor pO(2) and to determine the therapeutic outcomes when the timing of fractionations is guided by tumor pO(2). The time-course of the tumor pO(2) changes was followed by multi-site electron paramagnetic resonance (EPR) oximetry. The tumors were treat...
Article
Radio-toxins are toxic metabolites produced by ionizing irradiation and have toxic effects similar to those caused by direct irradiation. We have investigated the effect of a quinoid radio-toxin (QRT) obtained from gamma-irradiated potato tuber on various organs in mice using ex vivo and in vivo EPR spectroscopy. Results indicate a decrease in the...
Article
Full-text available
We have previously shown that seizures induce the formation of F(2)-isoprostanes (F(2)-IsoPs), one of the most reliable indices of oxidative stress in vivo. Isofurans (IsoFs) are novel products of lipid peroxidation whose formation is favored by high oxygen tensions. In contrast, high oxygen tensions suppress the formation of F(2)-IsoPs. The presen...
Article
Full-text available
Oxygen is an essential component for many aspects of tissue repair. However, the effect of oxygen levels on differentiation of stem cells into osteoblasts and chondrocytes during fracture healing is unknown, in part because of the difficulty in measuring oxygen during fracture healing. In this study we tested the feasibility of using electron param...
Article
In vivo electron paramagnetic resonance (EPR) spectroscopy can provide direct noninvasive, continuous, and repeatable measurements of oxygen in tissues. High-spatial-resolution multisite (HSRMS) oximetry is an EPR technique that uses applied magnetic field gradients to extend this capability to multiple implanted probes within the sample and accura...
Article
Efaproxiral, an allosteric modifier of hemoglobin, reduces hemoglobin-oxygen binding affinity, facilitating oxygen release from hemoglobin, which is likely to increase tissue pO(2). The purpose of this study was to determine the effect of efaproxiral on tumor oxygenation and growth inhibition of RIF-1 tumors that received X radiation (4 Gy) plus ox...
Article
Full-text available
Tissue oxygen plays a crucial role in maintaining tissue viability and in various diseases, including responses to therapy. Useful knowledge has been gained by methods that can give limited snapshots of tissue oxygen (e.g., oxygen electrodes) or evidence of a history of tissue hypoxia (e.g., EF5) or even indirect evidence by monitoring oxygen avail...
Article
We examined the effect of hyperbaric oxygen (HBO) and normobaric oxygen (NBO) on neurologic damage and brain oxygenation before and after focal cerebral ischemia in rats. A middle cerebral artery occlusion (MCAO)/reperfusion rat model was used. The rats were sacrificed 22 h after reperfusion, and the infarct volume was evaluated. In study A, HBO (2...
Article
Full-text available
The effects of two general anesthetics on skin oxygenation in mice are evaluated by electron paramagnetic resonance oximetry. Up to now no data on the effects of different anesthetics on skin oxygenation could be found. In this study animals were anesthetized with ketamine/xylazine or isoflurane, and partial pressure of oxygen (pO(2)) in the skin,...
Article
Electron paramagnetic resonance (EPR) oximetry is a powerful technology that allows the monitoring of oxygenation in tissues. The measurement of tissue oxygenation can be achieved using lithium phthalocyanine (LiPc) crystals as oxygen reporters. In order to have biocompatibility for the sensing system and to assure long-term stability in the respon...
Article
Electron paramagnetic resonance (EPR) oximetry is a promising, relatively non-invasive method of monitoring tissue partial pressure of oxygen (PtO(2)) that has proven useful in following changes in PtO(2) under various physiologic and pathophysiologic conditions. Optimal utilization of the method will be facilitated by systematic comparisons with o...
Article
To determine quantitatively the changes in oxygenation of intracranial tumors induced by efaproxiral, an allosteric hemoglobin modifier. Efaproxiral reduces hemoglobin-oxygen binding affinity, which facilitates oxygen release from hemoglobin into surrounding tissues and potentially increases the pO(2) of the tumors. The study was performed on 10 ma...
Article
Multi-site electron paramagnetic resonance (EPR) oximetry was used in vivo to measure the partial pressure of oxygen (pO2) in reversible focal ischemia in rats. The cerebral tissue pO2 was measured simultaneously and continuously at two sites on the ischemic side and one on the normal side of the brain in the same animal prior to and at several tim...
Article
It is known that oxygen tension in tissue (ptO2) will change in response to an alteration of physiological parameters including: pCO2 in arterial blood, blood flow, capillary density, oxygen carrying capacity, and p50 of hemoglobin. We have used modeling to compute the change of ptO2 in response to changes of each physiological parameter and relate...
Article
EPR oximetry is a technique that can make repeated non-invasive measurements of the PO2 in tissues. To extend the application of EPR oximetry to humans, India ink is the probe of choice because appropriate India inks have EPR signals whose line widths are sensitive to changes in oxygen concentrations, and, most importantly, India ink already has be...
Article
We describe our results on the effect in rats of two commonly used, volatile anesthetics on cerebral tissue PO2 (PtO2) and other physiological parameters at FiO2 levels ranging from 0.35 to 0.1. The study was performed in 12 rats that had lithium phthalocyanine (LiPc) crystals implanted in the left cerebral cortex. FiO2 was maintained at 0.35 durin...
Article
EPR oximetry is a promising, relatively non-invasive method for monitoring the partial pressure of oxygen in tissue (PtO2) that has proved useful in following changes under various physiologic and pathophysiologic conditions. Optimal utilization of the method will be facilitated by systematic comparisons with other available methods. Here we report...
Article
The development and use of in vivo techniques for strictly experimental applications in animals has been very successful, and these results now have made possible some very attractive potential clinical applications. The area with the most obvious immediate, effective and widespread clinical use is oximetry, where EPR almost uniquely can make repea...
Article
Full-text available
Oxygen tension (pO2) in muscles and regional blood flow were measured in a rabbit model of limb ischemia. pO2 was measured repetitively by EPR oximetry with EMS char in four different muscle groups in the same animals. Blood flow in the same muscles at several time points was measured using microspheres. A linear mixed effects model was developed t...