X-ray ionization and fragmentation for use with time-of-flight mass spectrometry

In this paper, we introduce laser desorption X-ray ionization for producing ions from the previously undetected neutral species present during laser desorption mass spectrometry. Studies involving the laser desorption of simple sugars were conducted to illustrate the differences between spectra with and without the X-ray source. Ionization was made possible by placing a 200 mCi Am X-ray source directly into the ionization chamber of a time-of-flight mass spectrometer.     

High-resolution near-infrared tomographic imaging simulations of the rat cranium by use of a priori magnetic resonance imaging structural information

Near-infrared (NIR) optical image reconstruction that incorporates magnetic resonance image (MRI) structural data was tested in a series of simulated reconstructions. NIR diffuse tomography generally suffers from comparatively low spatial resolution. By using the fine structural detail that is available with MRI, combined with the functional information of NIR spectroscopy, it is possible to design a new image-reconstruction methodology that provides high-resolution images that are correlated with hemoglobin concentration and oxygen saturation. To test this concept a MRI spin-echo image of a rat cranium was used to obtain an outline of the bone, brain, and muscle tissues, and this information was incorporated into an iterative-based diffuse tomography reconstruction. These simulations represent what is believed to be the first attempt at evaluating a spatially constrained iterative-reconstruction MRI-NIR imaging modality for brain tissue.     

Video-rate near-infrared optical tomography using spectrally encoded parallel light delivery

A novel parallel source implementation approach to near-infrared tomography is demonstrated through spectral encoding of the light delivery. This new technique allows many sources to be input into the tissue at the same time, and a high-resolution spectrometer is used to spatially spread out the signals from each spectrally encoded source. The parallel sampling of all sources at all detection locations renders rapid imaging. Acquisition of complete tomographic data sets at a video rate of 35 frames/s is achieved for imaging of a 6.35 mm diameter inclusion with an absorption coefficient of 0.01 mm(-1) and a reduced scattering coefficient of 1.5 mm(-1) that is moving along a circular path inside a 1% Intralipid solution.     

In vivo near-infrared spectral detection of pressure-induced changes in breast tissue

A diffuse near-infrared tomography system was used to measure dynamic changes in the absolute optical properties of the human breast that were induced through pressure applied to the tissue surface. Results from five subjects show that absorption and scattering coefficients changed measurably when pressure was increased and that these relative changes correlated with the subjects' body-mass index, indicating that the effect depends on tissue composition. Fitting the absolute absorption and scattering coefficients at six wavelengths to the molar absorption spectra of the three predominant chromophores revealed that both the average total hemoglobin and oxygen saturation increased by 10%, while water concentration decreased by more than 12%. These changes indicate that the pressure-induced variation is likely due to water displacement and vascular volume increase in the region being imaged, for mild application of pressure to the breast. These results suggest that the pressure applied during optical measurements of tissue may alter the tissue physiology, and care should be taken to factor this effect into the design of optical medical instrumentation. In addition, the technique provides a unique approach to measuring tissue elastic changes in vivo in the female breast and may offer a new method for dynamic contrast imaging based on elasto-optical measurements.     

Initial studies of in vivo absorbing and scattering heterogeneity in near-infrared tomographic breast imaging

Simultaneously recovered absorption and scattering images that separate these optical property features within the female breast are demonstrated from frequency-domain measurements. A study of known absorbing and scattering objects is presented as a foundation for interpreting these in vivo images once the contrast space has been fully characterized. No measurable influence of absorbing-object contrast appears in the scattering images, whereas localized scattering contrast enhances the corresponding region within the absorption image by approximately 30% (e.g., a 2:1 scatterer also reconstructs as an approximately 1.3:1 absorber). Scattering and absorption images of a female volunteer with a 3.4-cm fibroadenoma show a clear 2:1 localized increase in absorption coefficient with little or no evidence of scattering enhancement in the lesion.     

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.     

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.