Deferoxamine Iron Chelation Increases δ-Aminolevulinic Acid Induced Protoporphyrin IX in Xenograft Glioma Model

Exogenous administration of δ-aminolevulinic acid (δ-ALA) leads to selective accumulation of protoporphyrin IX (PpIX) in brain tumors, and has shown promising results in increasing extent of resection in fluorescence-guided resection (FGR) of brain tumors. However, this approach still suffers from heterogeneous staining and so some tumor margins may go undetected because of this variation in PpIX production. The aim of this study was to test the hypothesis that iron chelation therapy could increase the level of fluorescence in malignant glioma tumors. Mice implanted with xenograft U251-GFP glioma tumor cells were given a 200 mg kg⁻¹ dose of deferoxamine (DFO), once a day for 3 days prior to δ-ALA administration. The PpIX fluorescence observed in the tumor regions was 1.9 times the background in animal group without DFO, and 2.9 times the background on average, in the DFO pre-treated group. A 50% increase in PpIX fluorescence contrast in the DFO group was observed relative to the control group (t-test P-value = 0.0020). These results indicate that iron chelation therapy could significantly increase δ-ALA-induced PpIX fluorescence in malignant gliomas, pointing to a potential role of iron chelation therapy for more effective FGR of brain tumors.     

Energy transfer between surface-immobilized light-harvesting chlorophyll a/b complex (LHCII) studied by surface plasmon field-enhanced fluorescence spectroscopy (SPFS)

The major light-harvesting chlorophyll a/b complex (LHCII) of the photosynthetic apparatus in green plants can be viewed as a protein scaffold binding and positioning a large number of pigment molecules that combines rapid and efficient excitation energy transfer with effective protection of its pigments from photobleaching. These properties make LHCII potentially interesting as a light harvester (or a model thereof) in photoelectronic applications. Most of such applications would require the LHCII to be immobilized on a solid surface. In a previous study we showed the immobilization of recombinant LHCII on functionalized gold surfaces via a 6-histidine tag (His tag) in the protein moiety. In this work the occurrence and efficiency of Fo?rster energy transfer between immobilized LHCII on a functionalized surface have been analyzed by surface plasmon field-enhanced fluorescence spectroscopy (SPFS). A near-infrared dye was attached to some but not all of the LHC complexes, serving as an energy acceptor to chlorophylls. Analysis of the energy transfer from chlorophylls to this acceptor dye yielded information about the extent of intercomplex energy transfer between immobilized LHCII.     

Stability of superparamagnetic iron oxide nanoparticles at different pH values: experimental and theoretical analysis

The detection of superparamagnetic nanoparticles using NMR logging has the potential to provide enhanced contrast in oil reservoir rock formations. The stability of the nanoparticles is critical because the NMR relaxivity (R(2) ≡ 1/T(2)) is dependent on the particle size. Here we use a molecular theory to predict and validate experimentally the stability of citric acid-coated/PEGylated iron oxide nanoparticles under different pH conditions (pH 5, 7, 9, 11). The predicted value for the critical surface coverage required to produce a steric barrier of 5k(B)T for PEGylated nanoparticles (MW 2000) was 0.078 nm(-2), which is less than the experimental value of 0.143 nm(-2), implying that the nanoparticles should be stable at all pH values. Dynamic light scattering (DLS) measurements showed that the effective diameter did not increase at pH 7 or 9 after 30 days but increased at pH 11. The shifts in NMR relaxivity (from R(2) data) at 2 MHz agreed well with the changes in hydrodynamic diameter obtained from DLS data, indicating that the aggregation behavior of the nanoparticles can be easily and quantitatively detected by NMR. The unexpected aggregation at pH 11 is due to the desorption of the surface coating (citric acid or PEG) from the nanoparticle surface not accounted for in the theory. This study shows that the stability of the nanoparticles can be predicted by the theory and detected by NMR quantitatively, which suggests the nanoparticles to be a possible oil-field nanosensor.     

Spectrally resolved bioluminescence optical tomography

Spectrally resolved bioluminescence optical tomography is an approach to recover images of luciferase activity within a volume using multiwavelength emission data from internal bioluminescence sources. The underlying problem of uniqueness associated with nonspectrally resolved intensity-based bioluminescence tomography is highlighted. Reconstructed images of bioluminescence are presented by using as input both simulated and real multiwavelength data from a tissue-simulating phantom. The location of the internal bioluminescence is obtained with 1 mm accuracy. Further, the amplitude of the reconstructed source is proportional to the actual bioluminescence intensity.     

Rapid magnetic resonance-guided near-infrared mapping to image pulsatile hemoglobin in the breast

A near-IR (NIR) tomography system with spectral-encoded sources was built to quantify the temporal contrast in human breast tissue using guidance from magnetic resonance imaging. The systems were integrated with a custom breast coil interface to provide simultaneous acquisition. The NIR signal was synchronized to simultaneous finger pulse oximeter plethysmogram, which offered a frequency reference. A 0.1 s temporal delay of the absorption pulse within adipose tissue relative to fibroglandular tissue was found, in an initial human study, showing the potential for novel contrast imaging of fast flow signals in deep tissue.     

Temporal/spatial resolution improvement of in vivo DCE-MRI with compressed sensing-optimized FLASH

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) provides critical information regarding tumor perfusion and permeability by injecting a T(1) contrast agent, such as Gd-DTPA, and making a time-resolved measurement of signal increase. Both temporal and spatial resolutions are required to be high to achieve an accurate and reproducible estimation of tumor perfusion. However, the dynamic nature of the DCE experiment limits simultaneous improvement of temporal and spatial resolution by conventional methods. Compressed sensing (CS) has become an important tool for the acceleration of imaging times in MRI, which is achieved by enabling the reconstruction of subsampled data. Similarly, CS algorithms can be utilized to improve the temporal/spatial resolution of DCE-MRI, and several works describing retrospective simulations have demonstrated the feasibility of such improvements. In this study, the fast low angle shot sequence was modified to implement a Cartesian, CS-optimized, sub-Nyquist phase encoding acquisition/reconstruction with multiple two-dimensional slice selections and was tested on water phantoms and animal tumor models. The mean voxel-level concordance correlation coefficient for Ak(ep) values obtained from ×4 and ×8 accelerated and the fully sampled data was 0.87±0.11 and 0.83±0.11, respectively (n=6), with optimized CS parameters. In this case, the reduction of phase encoding steps made possible by CS reconstruction improved effectively the temporal/spatial resolution of DCE-MRI data using an in vivo animal tumor model (n=6) and may be useful for the investigation of accelerated acquisitions in preclinical and clinical DCE-MRI trials.     

A spectrally constrained dual-band normalization technique for protoporphyrin IX quantification in fluorescence-guided surgery

We report a dual-band normalization technique for in vivo quantification of the metabolic biomarker, protoporphyrin IX (PpIX), during brain tumor resection procedures. The accuracy of the approach was optimized in tissue simulating phantoms with varying absorption and scattering properties, validated with fluorimetric assessments on ex vivo brain tissue, and tested on human data acquired in vivo during fluorescence-guided surgery of brain tumors. The results demonstrate that the dual-band normalization technique allows PpIX concentrations to be accurately quantified by correction with reflectance data recorded and integrated within only two narrow wavelength intervals. The simplicity of the method lends itself to the enticing prospect that the method could be applicable to wide-field applications in quantitative fluorescence imaging and dosimetry in photodynamic therapy.     

Nuclear resonant scattering and molecular orbital calculations on an iron(II) spin‐crossover complex

Nuclear resonant scattering of synchrotron radiation was applied to investigate the spin‐crossover complex Fe(tpa)(NCS)₂ (tpa=tris(2‐pyridylmethyl)amine). The nuclear forward scattering experiments are compared with conventional Mössbauer experiments, and the nuclear inelastic scattering experiments are compared with the results from a theoretical normal mode analysis based on molecular orbital calculations.     

The spin cut-off factor for60Co

Nine experimental isomeric cross-section ratios for the reactions⁵⁹Co(n, γ)⁶⁰Co,⁶⁰Ni(n,p)⁶⁰Co, and⁶³Cu(n,α)⁶⁰Co are analysed in terms of statistical theory by means of the method ofHuizenga andVandenbosch. Theγ-cascades are treated by a new model which was recently published. The results confirm the energy dependence of the spin cut-off factor for⁶⁰Coσ～U^1/4 which should not be neglected. As a mean value (σ=4.3±0.3 is obtained forU=B _n =7.5 MeV in good agreement with a nuclear moment of inertia for a rigid sphere.