Chromium (VI) detection by microbial carbon dots: Microwave synthesis and mechanistic study.

Functionalized carbon dots (CDs) derived from Citrobacter freundii bacterial cells were used for selective detection of Cr(VI). A microwave-heating-based green synthesis approach is adopted to produce functionalized CDs from C. freundii bacterial cells (CF-CDs). The reaction was carried out in a 500 W microwave digester at 200°C for 20 min. The supernatant was filtered with a 0.2 µm filter and highly monodisperse CDs were obtained. Inherent functionalization of CF-CDs with nitrogen and oxygen-containing functional groups made them extremely selective toward Cr(VI) with a lower limit of detection of ~1.7 ppm. More importantly, CF-CDs could distinguish between Cr(VI) and Cr(III), which is highly desirable for practical applications. The fabricated sensor had a dual linear response range between 0 and 50 µM and 50-250 µM. The synthesized CDs were inherently functionalized which made them highly selective for Cr(VI) detection. CF-CDs also possess high stability over long storage period. This study reports the facile synthesis and characterization of a highly selective sensor for Cr(VI). As opposed to similar CDs sensors reported for Cr(VI), based on inner-filter effect, CF-CDs exhibit a strong, specific interaction toward Cr(VI), indicated by the large binding constant.

Multilevel population and socioeconomic variation in health insurance coverage in India.

OBJECTIVES: This study explores population-level variation in different types of health insurance coverage in India. We aimed to estimate the extent to which contextual factors at community, district, and state levels may contribute to place-based inequalities in coverage after accounting for household-level socioeconomic factors. METHODS: We used data from the 2015-2016 National Family Health Survey in India, which provides the most recent and comprehensive information available on reports of different types of household health insurance coverage. We used multilevel regression models to estimate the relative contribution of different population levels to variation in coverage by national, state, and private health insurance schemes. RESULTS: Among 601,509 households in India, 29% reported having coverage in 2015-2016. Variation in each type of coverage existed between population levels before and after adjusting for differences in the distribution of household socioeconomic and demographic factors. For example, the state level accounted for 36% of variation in national scheme coverage and 41% of variation in state scheme coverage after adjusting for household characteristics. In contrast, the community level was the largest contextual source of variation in private insurance coverage (accounting for 24%). Each type of coverage was associated with higher socioeconomic status and urban location. CONCLUSIONS: Contextual factors at community, district, and state levels contribute to variation in household health insurance coverage even after accounting for socioeconomic and demographic factors. Opportunities exist to reduce disparities in coverage by focusing on drivers of place-based differences at multiple population levels. Future research should assess whether new insurance schemes exacerbate or reduce place-based disparities in coverage.

EPR-based oximetric imaging: a combination of single point-based spatial encoding and T1 weighting.

PURPOSE: Spin-lattice relaxation rate (R1 )-based time-domain EPR oximetry is reported for in vivo applications using a paramagnetic probe, a trityl-based Oxo71. METHODS: The R1 dependence of the trityl probe Oxo71 on partial oxygen pressure (pO2 ) was assessed using single-point imaging mode of spatial encoding combined with rapid repetition, similar to T1 -weighted MRI, for which R1 was determined from 22 repetition times ranging from 2.1 to 40.0 µs at 300 MHz. The pO2 maps of a phantom with 3 tubes containing 2 mM Oxo71 solutions equilibrated at 0%, 2%, and 5% oxygen were determined by R1 and apparent spin-spin relaxation rate ( R2*) simultaneously. RESULTS: The pO2 maps derived from R1 and R2* agreed with the known pO2 levels in the tubes of Oxo71. However, the histograms of pO2 revealed that R1 offers better pO2 resolution than R2* in low pO2 regions. The SDs of pixels at 2% pO2 (15.2 mmHg) were about 5 times lower in R1 -based estimation than R2*-based estimation (mean ± SD: 13.9 ± 1.77 mmHg and 18.3 ± 8.70 mmHg, respectively). The in vivo pO2 map obtained from R1 -based assessment displayed a homogeneous profile in low pO2 regions in tumor xenografts, consistent with previous reports on R2*-based oximetric imaging. The scan time to obtain the R1 map can be significantly reduced using 3 repetition times ranging from 4.0 to 12.0 µs. CONCLUSION: Using the single-point imaging modality, R1 -based oximetry imaging with useful spatial and oxygen resolutions for small animals was demonstrated.

Patterning of individual heterogeneity in body mass index: evidence from 57 low- and middle-income countries.

Modeling variation at population level has become increasingly valued, but no clear application exists for modeling differential variation in health between individuals within a given population. We applied Goldstein's method (in: Everrit, Howell (eds) Encyclopedia of statistics in behavioral science, Wiley, Hoboken, 2005) to model individual heterogeneity in body mass index (BMI) as a function of basic sociodemographic characteristics, each independently and jointly. Our analytic sample consisted of 643,315 non-pregnant women aged 15-49 years pooled from the latest Demographic Health Surveys (rounds V, VI, or VII; years 2005-2014) across 57 low- and middle-income countries. Individual variability in BMI ranged from 9.8 (95% CI: 9.8, 9.9) for the youngest to 23.2 (95% CI: 22.9, 23.5) for the oldest age group; 14.2 (95% CI: 14.1, 14.3) for those with no formal education to 19.7 (95% CI: 19.5, 19.9) for those who have completed higher education; and 13.6 (95% CI: 13.5, 13.7) for the poorest quintile to 20.1 (95% CI: 20.0, 20.2) for the wealthiest quintile group. Moreover, variability in BMI by age was also different for different socioeconomic groups. Empirically testing the fundamental assumption of constant variance and identifying groups with systematically large differentials in health experiences have important implications for reducing health disparity.

Accelerated 4D quantitative single point EPR imaging using model-based reconstruction.

PURPOSE: Electron paramagnetic resonance imaging has surfaced as a promising noninvasive imaging modality that is capable of imaging tissue oxygenation. Due to extremely short spin-spin relaxation times, electron paramagnetic resonance imaging benefits from single-point imaging and inherently suffers from limited spatial and temporal resolution, preventing localization of small hypoxic tissues and differentiation of hypoxia dynamics, making accelerated imaging a crucial issue. METHODS: In this study, methods for accelerated single-point imaging were developed by combining a bilateral k-space extrapolation technique with model-based reconstruction that benefits from dense sampling in the parameter domain (measurement of the T2 (*) decay of a free induction delay). In bilateral kspace extrapolation, more k-space samples are obtained in a sparsely sampled region by bilaterally extrapolating data from temporally neighboring k-spaces. To improve the accuracy of T2 (*) estimation, a principal component analysis-based method was implemented. RESULTS: In a computer simulation and a phantom experiment, the proposed methods showed its capability for reliable T2 (*) estimation with high acceleration (8-fold, 15-fold, and 30-fold accelerations for 61×61×61, 95×95×95, and 127×127×127 matrix, respectively). CONCLUSION: By applying bilateral k-space extrapolation and model-based reconstruction, improved scan times with higher spatial resolution can be achieved in the current single-point electron paramagnetic resonance imaging modality.

Four-channel surface coil array for 300-MHz pulsed EPR imaging: proof-of-concept experiments.

Time-domain electron paramagnetic resonance imaging is currently a useful preclinical molecular imaging modality in experimental animals such as mice and is capable of quantitatively mapping hypoxia in tumor implants. The microseconds range relaxation times (T1 and T2) of paramagnetic tracers and the large bandwidths (tens of MHz) to be excited by electron paramagnetic resonance pulses for spatial encoding makes imaging of large objects a challenging task. The possibility of using multiple array coils to permit studies on large sized object is the purpose of the present work. Toward this end, the use of planar array coils in different configurations to image larger objects than cannot be fully covered by a single resonator element is explored. Multiple circular surface coils, which are arranged in a plane or at suitable angles mimicking a volume resonator, are used in imaging a phantom and a tumor-bearing mouse leg. The image was formed by combining the images collected from the individual coils with suitable scaling. The results support such a possibility. By multiplexing or interleaving the measurements from each element of such array resonators, one can scale up the size of the subject and at the same time reduce the radiofrequency power requirements and increase the sensitivity.

Basic studies on the role of components of Bacillus megaterium as flotation biocollectors in sulphide mineral separation.

Studies were carried out to assess the utility of the cellular and extracellular constituents of Bacillus megaterium for the flotation of sphalerite and galena minerals. Based on the flotation results on the individual minerals, it was observed that sphalerite was preferentially floated compared to galena. A maximum selectivity index (SI) value of 11.7 was achieved in the presence of the soluble fraction of the thermolysed cells, which was higher than that obtained with the intact cells (SI of 6.5) and the insoluble fraction of the thermolysed cells (SI of 9.6). The results of the various enzymatic treatment tests revealed that extracellular DNA played a vital role in the selective flotation of sphalerite. A noteworthy finding was that the single-stranded DNA (ssDNA) had a higher biocollector capacity vis-à-vis the double-stranded DNA (dsDNA), leading to better flotation efficiency. About 95 % recovery of sphalerite could be achieved from the mineral mixture by the combined addition of the ssDNA with the non-DNA components of the bacterial cells, resulting in a maximum SI of 19.1. Calcium and phosphate components of the nutrient media were found to be essential for better selectivity of separation of sphalerite. The mechanisms of microbe-mineral interaction are discussed.

Single acquisition quantitative single-point electron paramagnetic resonance imaging.

PURPOSE: Electron paramagnetic resonance imaging has emerged as a promising noninvasive technology to dynamically image tissue oxygenation. Owing to its extremely short spin-spin relaxation times, electron paramagnetic resonance imaging benefits from a single-point imaging scheme where the entire free induction decay signal is captured using pure phase encoding. However, direct T2 (*)/pO2 quantification is inhibited owing to constant magnitude gradients which result in time-decreasing field of view. Therefore, conventional acquisition techniques require repeated imaging experiments with differing gradient amplitudes (typically 3), which results in long acquisition time. METHODS: In this study, gridding was evaluated as a method to reconstruct images with equal field of view to enable direct T2 (*)/pO2 quantification within a single imaging experiment. Additionally, an enhanced reconstruction technique that shares high spatial k-space regions throughout different phase-encoding time delays was investigated (k-space extrapolation). RESULTS: The combined application of gridding and k-space extrapolation enables pixelwise quantification of T2 (*) from a single acquisition with improved image quality across a wide range of phase-encoding time delays. The calculated T2 (*)/pO2 does not vary across this time range. CONCLUSIONS: By utilizing gridding and k-space extrapolation, accurate T2 (*)/pO2 quantification can be achieved within a single data set to allow enhanced temporal resolution (by a factor of 3).

Evaluation of partial k-space strategies to speed up time-domain EPR imaging.

Narrow-line spin probes derived from the trityl radical have led to the development of fast in vivo time-domain EPR imaging. Pure phase-encoding imaging modalities based on the single-point imaging scheme have demonstrated the feasibility of three-dimensional oximetric images with functional information in minutes. In this article, we explore techniques to improve the temporal resolution and circumvent the relatively short biological half-lives of trityl probes using partial k-space strategies. There are two main approaches: one involves the use of the Hermitian character of the k-space by which only part of the k-space is measured and the unmeasured part is generated using the Hermitian symmetry. This approach is limited in success by the accuracy of numerical estimate of the phase roll in the k-space that corrupts the Hermiticy. The other approach is to measure only a judicially chosen reduced region of k-space (a centrosymmetric ellipsoid region) that more or less accounts for >70% of the k-space energy. Both of these aspects were explored in Fourier transform-EPR imaging with a doubling of scan speed demonstrated by considering ellipsoid geometry of the k-space. Partial k-space strategies help improve the temporal resolution in studying fast dynamics of functional aspects in vivo with infused spin probes.

EPR oxygen imaging and hyperpolarized 13C MRI of pyruvate metabolism as noninvasive biomarkers of tumor treatment response to a glycolysis inhibitor 3-bromopyruvate.

The hypoxic nature of tumors results in treatment resistance and poor prognosis. To spare limited oxygen for more crucial pathways, hypoxic cancerous cells suppress mitochondrial oxidative phosphorylation and promote glycolysis for energy production. Thereby, inhibition of glycolysis has the potential to overcome treatment resistance of hypoxic tumors. Here, EPR imaging was used to evaluate oxygen dependent efficacy on hypoxia-sensitive drug. The small molecule 3-bromopyruvate blocks glycolysis pathway by inhibiting hypoxia inducible enzymes and enhanced cytotoxicity of 3-bromopyruvate under hypoxic conditions has been reported in vitro. However, the efficacy of 3-bromopyruvate was substantially attenuated in hypoxic tumor regions (pO2<10 mmHg) in vivo using squamous cell carcinoma (SCCVII)-bearing mouse model. Metabolic MRI studies using hyperpolarized 13C-labeled pyruvate showed that monocarboxylate transporter-1 is the major transporter for pyruvate and the analog 3-bromopyruvate in SCCVII tumor. The discrepant results between in vitro and in vivo data were attributed to biphasic oxygen dependent expression of monocarboxylate transporter-1 in vivo. Expression of monocarboxylate transporter-1 was enhanced in moderately hypoxic (8-15 mmHg) tumor regions but down regulated in severely hypoxic (<5 mmHg) tumor regions. These results emphasize the importance of noninvasive imaging biomarkers to confirm the action of hypoxia-activated drugs.

The Brazilian vaccine divide: How some municipalities were left behind in the Covid-19 vaccine coverage.

This study aims to assess the progress of geographic, socioeconomic, and demographic disparities in Covid-19 vaccination coverage in Brazil over the first two years of the vaccination campaign. Data from the National Immunization Program Information System were used to estimate covid-19 vaccine coverage. Brazilian municipalities were divided into two groups based on their vaccine coverage for the booster dose. The first group comprised 20% of municipalities with the lowest coverage, while the second group (80% of municipalities) had higher coverage. The analysis was conducted separately for four age groups: 5-11, 12-17, 18-59, and 60+. Explanatory variables included socioeconomic and health services indicators. Crude and adjusted logistic regression models were used to estimate the probability of a municipality being among those with the worst vaccination coverage according to the categories of exploratory variables. Between January/2021 and December/2022, Brazil administered 448.2 million doses of the covid-19 vaccine. The booster vaccination coverage varied from 24.8% among adolescents to 79.7% among the elderly. The difference between the group with the highest and lowest coverage increased during the national vaccination campaign. Municipalities with lower education levels, higher proportion of Black population, higher Gini index, and worse health service indicators had a greater likelihood of having lower vaccination coverage. High and increasing levels of inequality in Covid-19 vaccination were observed in Brazil across all age groups during the vaccination campaign in 2021-2022.

Transient decrease in tumor oxygenation after intravenous administration of pyruvate.

MRI using hyperpolarized (13) C-labeled pyruvate is a promising tool to biochemically profile tumors and monitor their response to therapy. This technique requires injection of pyruvate into tumor-bearing animals. Pyruvate is an endogenous entity but the influence of exogenously injected bolus doses of pyruvate on tumor microenvironment is not well understood. In this study, the effect of injecting a bolus of pyruvate on tumor oxygen status was investigated. EPR oxygen imaging revealed that the partial pressure of oxygen (pO(2)) in squamous cell carcinoma implanted in mice decreased significantly 30 min after [1-(13) C]pyruvate injection, but recovered to preinjection levels after 5 h. Dynamic contrast-enhanced-MRI studies showed that, at the dose of pyruvate used, no changes in tumor perfusion were noticed. Immunohistochemical analysis of hypoxic marker pimonidazole independently verified that the squamous cell carcinoma tumor transiently became more hypoxic by pyruvate injection. Efficacy of radiotherapy was suppressed when X-irradiation was delivered during the period of pyruvate-induced transient hypoxia. These results suggest importance of taking into account the transient decrease in tumor pO(2) after pyruvate injection in hyperpolarized (13) C MRI, because tumor oxygen status is an important factor in determining outcomes of therapies.

Simultaneous imaging of tumor oxygenation and microvascular permeability using Overhauser enhanced MRI.

Architectural and functional abnormalities of blood vessels are a common feature in tumors. A consequence of increased vascular permeability and concomitant aberrant blood flow is poor delivery of oxygen and drugs, which is associated with treatment resistance. In the present study, we describe a strategy to simultaneously visualize tissue oxygen concentration and microvascular permeability by using a hyperpolarized (1)H-MRI, known as Overhauser enhanced MRI (OMRI), and an oxygen-sensitive contrast agent OX63. Substantial MRI signal enhancement was induced by dynamic nuclear polarization (DNP). The DNP achieved up to a 7,000% increase in MRI signal at an OX63 concentration of 1.5 mM compared with that under thermal equilibrium state. The extent of hyperpolarization is influenced mainly by the local concentration of OX63 and inversely by the tissue oxygen level. By collecting dynamic OMRI images at different hyperpolarization levels, local oxygen concentration and microvascular permeability of OX63 can be simultaneously determined. Application of this modality to murine tumors revealed that tumor regions with high vascular permeability were spatio-temporally coincident with hypoxia. Quantitative analysis of image data from individual animals showed an inverse correlation between tumor vascular leakage and median oxygen concentration. Immunohistochemical analyses of tumor tissues obtained from the same animals after OMRI experiments demonstrated that lack of integrity in tumor blood vessels was associated with increased tumor microvascular permeability. This dual imaging technique may be useful for the longitudinal assessment of changes in tumor vascular function and oxygenation in response to chemotherapy, radiotherapy, or antiangiogenic treatment.

Mixed Effect of Alcohol, Smoking, and Smokeless Tobacco Use on Hypertension among Adult Population in India: A Nationally Representative Cross-Sectional Study.

Sporadic evidence is available on the association of consuming multiple substances with the risk of hypertension among adults in India where there is a substantial rise in cases. This study assesses the mutually exclusive and mixed consumption patterns of alcohol, tobacco smoking and smokeless tobacco use and their association with hypertension among the adult population in India. Nationally representative samples of men and women drawn from the National Family and Health Survey (2015-2016) were analyzed. A clinical blood pressure measurement above 140 mmHg (systolic blood pressure) and 90 mmHg (diastolic blood pressure) was considered in the study as hypertension. Association between mutually exclusive categories of alcohol, tobacco smoking and smokeless tobacco and hypertension were examined using multivariate binary logistic regression models. Daily consumption of alcohol among male smokeless tobacco users had the highest likelihood to be hypertensive (OR: 2.32, 95% CI: 1.99-2.71) compared to the no-substance-users. Women who smoked, and those who used any smokeless tobacco with a daily intake of alcohol had 71% (OR: 1.71, 95% CI: 1.14-2.56) and 51% (OR: 1.51, 95% CI: 1.25-1.82) higher probability of being hypertensive compared to the no-substance-users, respectively. In order to curb the burden of hypertension among the population, there is a need for an integrated and more focused intervention addressing the consumption behavior of alcohol and tobacco.

Low-field paramagnetic resonance imaging of tumor oxygenation and glycolytic activity in mice.

A priori knowledge of spatial and temporal changes in partial pressure of oxygen (oxygenation; pO(2)) in solid tumors, a key prognostic factor in cancer treatment outcome, could greatly improve treatment planning in radiotherapy and chemotherapy. Pulsed electron paramagnetic resonance imaging (EPRI) provides quantitative 3D maps of tissue pO(2) in living objects. In this study, we implemented an EPRI set-up that could acquire pO(2) maps in almost real time for 2D and in minutes for 3D. We also designed a combined EPRI and MRI system that enabled generation of pO(2) maps with anatomic guidance. Using EPRI and an air/carbogen (95% O(2) plus 5% CO(2)) breathing cycle, we visualized perfusion-limited hypoxia in murine tumors. The relationship between tumor blood perfusion and pO(2) status was examined, and it was found that significant hypoxia existed even in regions that exhibited blood flow. In addition, high levels of lactate were identified even in normoxic tumor regions, suggesting the predominance of aerobic glycolysis in murine tumors. This report presents a rapid, noninvasive method to obtain quantitative maps of pO(2) in tumors, reported with anatomy, with precision. In addition, this method may also be useful for studying the relationship between pO(2) status and tumor-specific phenotypes such as aerobic glycolysis.

Intracellular hypoxia of tumor tissue estimated by noninvasive electron paramagnetic resonance oximetry technique using paramagnetic probes.

Electron paramagnetic resonance (EPR) oximetry at 700 MHz operating frequency employing a surface coil resonator is used to assess tissue partial pressure of oxygen (pO(2)) using paramagnetic media whose linewidth and decay constant are related to oxygen concentration. Differences in extracellular and intracellular pO(2) in squamous cell carcinoma (SCC) tumor tissue were tested using several types of water-soluble paramagnetic media, which localize extracellularly or permeate through the cell membrane. The nitroxide carboxy-PROXYL (CxP) can only be distributed in blood plasma and extracellular fluids whereas the nitroxides carbamoyl-PROXYL (CmP) and TEMPOL (TPL) can permeate cell membranes and localize intracellularly. EPR signal decay constant and the linewidth of the intravenously administered nitroxides in SCC tumor tissues implanted in mouse thigh and the contralateral normal muscle of healthy mice breathing gases with different pO(2) were compared. The pO(2) in the blood can depend on the oxygen content in the breathing gas while tissue pO(2) was not directly influenced by pO(2) in the breathing gas. The decay constants of CmP and TPL in tumor tissue were significantly larger than in the normal muscles, and lower linewidths of CmP and TPL in tumor tissue was observed. The SCC tumor showed intracellular hypoxia even though the extracellular pO(2) is similar to normal tissue in the peripheral region.

Towards reduction of SAR in scaling up in vivo pulsed EPR imaging to larger objects.

An excessive RF power requirement is one of the main obstacles in the clinical translation of EPR imaging. The radio frequency (RF) pulses used in EPR imaging to excite electron spins must be very short to match their fast relaxation. With traditional pulse schemes and ninety degree flip angles, this can lead to either unsafe specific absorption rate (SAR) levels or unfeasibly long repetition times. In spectroscopy experiments, it has been shown that stochastic excitation and correlation detection can reduce the power while maintaining sensitivity but have yet to be applied to imaging experiments. Stochastic excitation is implemented using a pseudo-random phase modulation of the input stimulus. Using a crossed coil resonator assembly comprised of an outer saddle coil and an inner surface coil, it was possible to obtain a minimum isolation of ∼50 dB across a 12 MHz bandwidth. An incident peak RF power of 5 mW was used to excite the system. The low background signal obtained from this resonator allowed us to generate images with 32 dB (>1000:1) signal-to-noise ratio (SNR) while exciting with a traditional pulse sequence in a phantom containing the solid paramagnetic probe NMP-TCNQ (N-methyl pyridinium tetracyanoquinodimethane). Using two different stochastic excitation schemes, we were able to achieve a greater than 4-fold increase in SNR at the same peak power and number of averages, compared to single pulse excitation. This procedure allowed imaging at significantly lower RF power levels than used in conventional EPR imaging system configurations. Similar techniques may enable clinical applications for EPR imaging by facilitating the use of larger RF coils while maintaining a safe SAR level.

Monitoring redox-sensitive paramagnetic contrast agent by EPRI, OMRI and MRI.

A comparative study of tissue redox-status imaging using commonly used redox sensitive nitroxides has been carried out using electron paramagnetic resonance imaging (EPRI), Overhauser magnetic resonance imaging (OMRI) and conventional T(1)-weighted magnetic resonance imaging, MRI. Imaging studies using phantoms of different nitroxides at different concentration levels showed that EPRI and OMRI sensitivities were found to be linearly dependent on line width of nitroxides up to 2 mM, and the enhancement in MRI intensity was linear up to 5 mM. The sensitivity and resolution of EPRI and OMRI images depended significantly on the line width of the nitroxides whereas the MRI images were almost independent of EPR line width. Reduction of the paramagnetic 3-carbamoyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl (3CP) by ascorbic acid (AsA) to the diamagnetic by hydroxylamine was monitored from a sequence of temporal images, acquired using the three imaging modalities. The decay rates determined by all the three modalities were found to be similar. However the results suggest that T(1)-weighted MRI can monitor the redox status, in addition to providing detailed anatomical structure in a short time. Therefore, a combination of MRI with nitroxides as metabolically responsive contrast agents can be a useful technique for the in vivo imaging probing tissue redox status.

Spatially resolved biologic information from in vivo EPRI, OMRI, and MRI.

EPR spectroscopy can give biologically important information, such as tissue redox status, pO2, pH, and microviscosity, based on variation of EPR spectral characteristics (i.e., intensity, linewidth, hyperfine splitting, and spectral shape of free radical probes. EPR imaging (EPRI) can obtain 1D-3D spatial distribution of such spectral components using several combinations of magnetic field gradients. Overhauser enhanced MRI (OMRI) is a double-resonance technique of electron and nuclear spins. Because the Overhauser enhancement depends on transverse relaxation rate of the electron spin, OMRI can provide pO2 information indirectly, along with a high-resolution MR image. MRI can also indirectly detect paramagnetic behaviors of free radical contrast agents. Imaging techniques and applications relating to paramagnetic species (i.e., EPRI, OMRI, and MRI) have the potential to obtain maximally 5D information (i.e., 3D spatial + 1D spectral + 1D temporal dimensions, theoretically). To obtain suitable dimensionality, several factors, such as the EPR spectral information, spatial resolution, temporal resolution, will have to be taken into account. For this review, the EPRI, OMRI, and MRI applications for the study biological systems were evaluated for researchers to apply the method of choice and the mode of measurements to specific experimental systems.

Continuous wave EPR oximetric imaging at 300 MHz using radiofrequency power saturation effects.

A novel continuous wave (CW), radiofrequency (RF), electron paramagnetic resonance (EPR) oximetric imaging technique is proposed, based on the influence of oxygen concentration on the RF power saturation of the EPR resonance. A linear relationship is demonstrated between the partial oxygen pressure (pO(2)) and the normalized signal intensity (I(N)), defined as, I(N) = (I(HP) - I(LP))/I(LP), where I(LP) and I(HP) refer to signal intensities at low (P(L)) and high (P(H)) RF power levels, respectively. A formula for the determination of pO(2), derived on the basis of the experimental results, reliably estimated various oxygen concentrations in a five-tube phantom. This new technique was time-efficient and also avoided the missing angle problem associated with conventional spectral-spatial CW EPR oximetric imaging. In vivo power saturation oximetric imaging in a tumor bearing mouse clearly depicted the hypoxic foci within the tumor.