Optimization of Detection of Gadodiamide Brain Retention in Rats Using Quantitative T2 Mapping and Intraperitoneal Administration.

BACKGROUND: Currently, the gadolinium retention in the brain after the use of contrast agents is studied by T1 -weighted magnetic resonance imaging (MRI) (T1 w) and T1 mapping. The former does not provide easily quantifiable data and the latter requires prolonged scanning and is sensitive to motion. T2 mapping may provide an alternative approach. Animal studies of gadolinium retention are complicated by repeated intravenous (IV) dosing, whereas intraperitoneal (IP) injections might be sufficient. HYPOTHESIS: T2 mapping will detect the changes in the rat brain due to gadolinium retention, and IP administration is equivalent to IV for long-term studies. STUDY TYPE: Prospective longitudinal. ANIMAL MODEL: A total of 31 Sprague-Dawley rats administered gadodiamide IV (N = 8) or IP (N = 8), or saline IV (N = 6) or IP (N = 9) 4 days per week for 5 weeks. FIELD STRENGTH/SEQUENCES: A 7 T, T1 w, and T2 mapping. ASSESSMENT: T2 relaxation and image intensities in the deep cerebellar nuclei were measured pre-treatment and weekly for 5 weeks. Then brains were assessed for neuropathology (N = 4) or gadolinium content using inductively coupled plasma mass spectrometry (ICP-MS, N = 12). STATISTICAL TESTS: Repeated measures analysis of variance with post hoc Student-Newman-Keuls tests and Hedges' effect size. RESULTS: Gadolinium was detected by both approaches; however, T2 mapping was more sensitive (effect size 2.32 for T2 vs. 0.95 for T1 w), and earlier detection (week 3 for T2 vs. week 4 for T1 w). ICP-MS confirmed the presence of gadolinium (3.076 ± 0.909 nmol/g in the IV group and 3.948 ± 0.806 nmol/g in the IP group). There was no significant difference between IP and IV groups (ICP-MS, P = 0.109; MRI, P = 0.696). No histopathological abnormalities were detected in any studied animal. CONCLUSION: T2 relaxometry detects gadolinium retention in the rat brain after multiple doses of gadodiamide irrespective of the route of administration. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 1.

Cytotoxicity and genotoxicity of cadmium oxide nanoparticles evaluated using in vitro assays.

Cadmium oxide nanoparticles (CdO NPs) are among some of the most studied and industrially used metal oxide NPs. They have been widely used for industrial application, such as paint pigments and electronic devices, and medical therapeutics. With increasing use of CdO NPs and concerns for their potential adverse effects on the environment and public health, evaluation of the cytotoxicity and genotoxicity of CdO NPs becomes very important. To date, there is a limited understanding of the potential hazard brought by CdO NPs and a lack of information and research, particularly on the genotoxicity assessment of these NPs. In this study, 10 nm CdO core-PEG stabilized NPs were synthesized, characterized and used for evaluation of CdO NPs' cytotoxicity and genotoxicity. Release of cadmium ions (Cd+2) from the CdO NPs in cell culture medium, cellular uptake of the NPs, and the endotoxin content of the particles were measured prior to the toxicity assays. Cytotoxicity was evaluated using the MTS assay, ATP content detection assay, and LDH assay. Genotoxicity was assessed using the Ames test, Comet assay, micronucleus assay, and mouse lymphoma assay. The cytotoxicity of cadmium chloride (CdCl2) was also evaluated along with that of the CdO NPs. The results showed that endotoxin levels within the CdO NPs were below the limit of detection. CdO NPs induced concentration-dependent cytotoxicity in TK6 and HepG2 cells with the MTS, ATP and LDH assays. Although the genotoxicity of CdO NPs was negative in the Ames test, positive results were obtained with the micronucleus, Comet, and mouse lymphoma assays. The negative response of CdO NPs with the Ames test may be the result of unsuitability of the assay for measuring NPs, while the positive responses from other genotoxicity assays suggest that CdO NPs can induce chromosomal damage, single or double strand breaks in DNA, and mutations. The toxicity of the CdO NPs results from the NPs themselves and not from the released Cd+2, because the ions released from the NPs were minimal. These results demonstrate that CdO NPs are cytotoxic and genotoxic and provide new insights into risk assessment of CdO NPs for human exposure and environmental protection.

Sierpinski Pyramids by Molecular Entanglement.

Planar, terpyridine-based metal complexes with the Sierpinski triangular motif and alkylated corners undergo a second self-assembly event to give megastructural Sierpinski pyramids; assembly is driven by the facile lipophilic-lipophilic association of the alkyl moieties and complementary perfect fit of the triangular building blocks. Confirmation of the 3D, pyramidal structures was verified and supported by a combination of TEM, AFM, and multiscale simulation techniques.

High resolution laser mass spectrometry bioimaging.

Mass spectrometry imaging (MSI) was introduced more than five decades ago with secondary ion mass spectrometry (SIMS) and a decade later with laser desorption/ionization (LDI) mass spectrometry (MS). Large biomolecule imaging by matrix-assisted laser desorption/ionization (MALDI) was developed in the 1990s and ambient laser MS a decade ago. Although SIMS has been capable of imaging with a moderate mass range at sub-micrometer lateral resolution from its inception, laser MS requires additional effort to achieve a lateral resolution of 10µm or below which is required to image at the size scale of single mammalian cells. This review covers untargeted large biomolecule MSI using lasers for desorption/ionization or laser desorption and post-ionization. These methods include laser microprobe (LDI) MSI, MALDI MSI, laser ambient and atmospheric pressure MSI, and near-field laser ablation MS. Novel approaches to improving lateral resolution are discussed, including oversampling, beam shaping, transmission geometry, reflective and through-hole objectives, microscope mode, and near-field optics.

Laser desorption sample transfer for gas chromatography/mass spectrometry.

RATIONALE: Ambient mass spectrometry can detect small molecules directly, but complex mixtures can be a challenge. We have developed a method that incorporates small molecule separation based on laser desorption with capture on a solid-phase microextraction (SPME) fiber for injection into a gas chromatography/mass spectrometry (GC/MS) system. METHODS: Samples on a metal target were desorbed by a 3 µm mid-infrared laser focused to a 250 µm spot and 1.2 mJ pulse energy. The desorbed material was aspirated into a metal tube suspended 1 mm above the laser spot and captured on a SPME fiber. The collected material was injected into a GC/MS instrument for analysis. RESULTS: We have developed a versatile approach for ambient laser desorption sampling onto SPME for GC/MS analysis. The performance of the laser desorption SPME capture GC/MS system was demonstrated for small molecule standards, a mixture of nitroaromatic explosives, and collected cigarette smoke. CONCLUSIONS: The utility of ambient laser desorption sampling onto SPME for GC/MS was demonstrated. The performance of the method was evaluated by preparing calibration standards of caffeine over a range from 200 to 1000 ng. Laser desorption ambient sampling of complex mixtures was accomplished using SPME GC/MS.

Mechanical Properties of a Series of Macro- and Nanodimensional Organic Cocrystals Correlate with Atomic Polarizability.

A correlation between Young's modulus, as determined by using nanoindentation atomic force microscopy (AFM), and atomic polarizability is observed for members of a series of cocrystals based on systematic changes to one cocrystal component. Time domain spectroscopy over terahertz frequencies (THz-TDS) is used for the first time to directly measure the polarizability of macro- and nanosized organic solids. Cocrystals of both macro- and nanodimensions with highly polarizable atoms result in softer solids and correspondingly higher polarizabilities.

Tip-enhanced laser ablation sample transfer for biomolecule mass spectrometry.

Atomic force microscope (AFM) tip-enhanced laser ablation was used to transfer molecules from thin films to a suspended silver wire for off-line mass spectrometry using laser desorption ionization (LDI) and matrix-assisted laser desorption ionization (MALDI). An AFM with a 30 nm radius gold-coated silicon tip was used to image the sample and to hold the tip 15 nm from the surface for material removal using a 355 nm Nd:YAG laser. The ablated material was captured on a silver wire that was held 300 µm vertically and 100 µm horizontally from the tip. For the small molecules anthracene and rhodamine 6G, the wire was cut and affixed to a metal target using double-sided conductive tape and analyzed by LDI using a commercial laser desorption time-of-flight mass spectrometer. Approximately 100 fg of material was ablated from each of the 1 µm ablation spots and transferred with approximately 3% efficiency. For larger polypeptide molecules angiotensin II and bovine insulin, the captured material was dissolved in saturated matrix solution and deposited on a target for MALDI analysis.

Hygroscopic properties of internally mixed particles composed of NaCl and water-soluble organic acids.

Atmospheric aging of naturally emitted marine aerosol often leads to formation of internally mixed particles composed of sea salts and water-soluble organic compounds of anthropogenic origin. Mixing of sea salt and organic components has profound effects on the evolving chemical composition and hygroscopic properties of the resulted particles, which are poorly understood. Here, we have studied chemical composition and hygroscopic properties of laboratory generated NaCl particles mixed with malonic acid (MA) and glutaric acid (GA) at different molar ratios using micro-FTIR spectroscopy, atomic force microscopy, and X-ray elemental microanalysis. Hygroscopic properties of internally mixed NaCl and organic acid particles were distinctly different from pure components and varied significantly with the type and amount of organic compound present. Experimental results were in a good agreement with the AIM modeling calculations of gas/liquid/solid partitioning in studied systems. X-ray elemental microanalysis of particles showed that Cl/Na ratio decreased with increasing organic acid component in the particles with MA yielding lower ratios relative to GA. We attribute the depletion of chloride to the formation of sodium malonate and sodium glutarate salts resulted by HCl evaporation from dehydrating particles.

Intraluminal urethral brachytherapy for recurrence of transitional cell carcinoma of urinary bladder in urethral stump.

We report a unique case of successfully performed intraluminal brachytherapy for low volume urethral mucosal recurrence of transitional cell carcinoma urinary bladder, initially treated by transurethral resection of bladder tumor, followed by radical cystectomy. Since the patient was unwilling to undergo any other operational interventions, intraluminal brachytherapy of urethra was attempted. Fluroscopy guided intraluminal HDR brachytherapy using Lumencath(®) catheter under local anesthesia, and remote afterloading system (Nucletron, an Elekta company, Elekta AB, Stockholm, Sweden) was performed. A fraction dose of 7 Gy in seven weekly fractions was prescribed at 0.5 cm from the single applicator. The result was promising in terms of local control and symptomatic relief. Therefore, intraluminal brachytherapy in low volume superficial local disease in urethra may play a potential role, and should be applied when repeated surgery is not feasible due to technical or medical reasons.

A comparison of dose distribution from Manchester-style and Fletcher-style intracavitary brachytherapy applicator systems in cervical cancer.

PURPOSE: During intracavitary brachytherapy (ICBT) for cervical cancer, the choice of applicator system remains rather arbitrary. However, as the applicator geometry may play an important role in dose distribution, thereby improving the therapeutic ratio, this study was conducted to compare the Manchester-style and Fletcher-style applicator systems. MATERIAL AND METHODS: After completion of EBRT, 22 patients with cervical cancer (stage IIA-IIIB) underwent intracavitary brachytherapy. Two different types of applicators: Manchester-style and Fletcher-style were used for each patient for alternate insertions. The purpose was to compare the dose distribution obtained when two different applicators were applied to the same patient. CT based computerized treatment planning was done and dose was prescribed to point A. After optimization, height, width and thickness of the 100% isodose curve, as well as the 100% isodose volume were noted. Dose received by the urinary bladder and rectum were noted. RESULTS: The 100% isodose volume and its maximum width were significantly greater (P value < 0.0001 in both occasions) when Manchester-style applicator was used. However, the dose received by 0.1 cc, 1.0 cc and 2.0 cc of the urinary bladder were all significantly greater (P value < 0.0001) with the Manchester-style applicator. No significant difference was found in rectal doses. CONCLUSIONS: The larger 100% isodose volume, as well as the greater width achieved with the use of Manchester-style applicator can be helpful in circumstances where the tumour is large in size. However, this must be balanced against the increased dose received by the urinary bladder.

Spectroscopic evidence of keto-enol tautomerism in deliquesced malonic acid particles.

Scanning transmission X-ray microscopy combined with near-edge X-ray absorption fine structure spectroscopy (STXM/NEXAFS) and optical microscopy coupled with Fourier transform infrared spectroscopy (micro-FTIR) have been applied to observe hygroscopic growth and chemical changes in malonic acid particles deposited on substrates. The extent of the hygroscopic growth of particles has been quantified in terms of the corresponding water-to-solute ratios (WSR) based on STXM/NEXAFS and micro-FTIR data sets. WSR values derived separately from two applied methods displayed a remarkable agreement with previous data reported in the literature. Comparison of NEXAFS and FTIR spectra acquired at different relative humidity (RH) shows efficient keto-enol tautomerization of malonic acid, with the enol form dominating at higher RH. The keto-enol equilibrium constants were calculated using relevant peak intensities in the carbon and oxygen K-edge NEXAFS spectra as a function of RH. We report strong dependence of the equilibrium constant on RH, with measured values of 0.18 ± 0.03, 1.11 ± 0.14, and 2.33 ± 0.37 corresponding to 2, 50, and 90% RH, respectively. Enols are important intermediates in aldol condensation reactions pertaining to formation and atmospheric aging of secondary organic aerosol (SOA). The present knowledge assumes that constituents of atmospheric deliquesced particles undergo aqueous chemistry with kinetic and equilibrium constants analogous to reactions in bulk solutions, which would estimate absolute dominance of the keto form of carboxylic acids. For instance, the keto-enol equilibrium constant of malonic acid in diluted aqueous solution is <10(-4). Our results suggest that in deliquesced micrometer-size particles, carboxylic acids may exist in predominantly enol forms that need to be explicitly considered in atmospheric aerosol chemistry.

Thixotropic hydrogel derived from a product of an organic solid-state synthesis: properties and densities of metal-organic nanoparticles.

Metallogels form from Cu(II) ions and tetratopic ligand rctt-1,2-bis(3-pyridyl)-3,4-bis(4-pyridyl)cyclobutane. The tetrapyridyl cyclobutane has been synthesized in the organic solid state. The gel forms with a variety of counteranions and gels water. The hydrogel is thixotropic and is composed of nanoscale metal-organic particles (NMOPs), a high surface area of which likely accounts for the gelation of the polar aqueous medium. A shear stress profile of the thixotropic hydrogel gave a yield value of 8.33 Pa. A novel combination of atomic force microscopy (AFM) and scanning transmission X-ray microscopy (STXM) is used to assess the densities of individual NMOPs. A density of 1.37 g/cm(3) has been determined. A single-crystal X-ray diffraction study demonstrates the ability of the unsymmetrical cyclobutane 3,4'-tpcb to self-assemble with Cu(II) ions in [Cu(2)(hfac)(4)(3,4'-tpcb)](∞) (where hfac is hexafluoroacetylacetonate) to form a solvated 1D coordination polymer.

Hygroscopic behavior of individual submicrometer particles studied by X-ray spectromicroscopy.

A novel application of single particle scanning transmission X-ray microscopy (STXM) and near edge X-ray absorption fine structure (NEXAFS) spectroscopy is presented for quantitative analysis of hygroscopic properties and phase transitions of individual submicrometer particles. The approach utilizes the exposure of substrate-deposited individual particles to water vapor at different relative humidity followed by STXM/NEXAFS spectromicroscopy analysis. The hygroscopic properties of atmospherically relevant NaCl, NaBr, NaI, and NaNO(3) submicrometer particles were measured to evaluate the utility of the approach. An analytical approach for quantification of a water-to-solute ratio within an individual submicrometer particle during hydration and dehydration cycles is presented. The results for the deliquescence and efflorescence phase transitions and quantitative measurements of water-to-solute ratios are found in excellent agreement with available literature data. Oxygen K-edge NEXAFS spectra of submicrometer sodium halide droplets are reported along with a unique experimental observation of the formation of the halide-water anionic complex in NaBr and NaI microdimensional droplets. The analytical approach provides a unique opportunity for spectromicroscopy studies of water uptake on environmental particles collected in both laboratory and field studies.

Late nodal metastasis in early-stage node-negative oral cavity cancers after successful sole interstitial brachytherapy: an institutional experience of 42 cases in India.

PURPOSES: Brachytherapy, either alone or in combination with external irradiation, is a useful organ-preserving approach in the treatment of primary head and neck cancers. Treatment of regional nodal drainage area is not warranted in early-stage oral cavity cancers because T1N0 oral cavity cancers have less than 20% likelihood of nodal spread. We reviewed the records of interstitial brachytherapy cases of oral cavity cancers in our brachytherapy unit to assess the clinical outcome of the patients treated. METHODS AND MATERIALS: We tried to correlate the clinical outcome of the disease with different predictive factors for treatment outcome and to analyze statistically the role of these factors. RESULTS: Cases treated with combined external irradiation with interstitial brachytherapy included higher T stage, with greater risk for nodal spread, though initially node negative. As these were treated with microscopic dose for nodal clinical target volume, nodal recurrence was fewer (18.5%). On the contrary, although the early-stage (T1N0) oral cavity cancers that were treated with brachytherapy alone had initially a less than 20% chance of nodal metastasis, there was an increased risk up to 80% for late nodal metastasis after treatment. Tumor thickness >6mm (p=0.044) and need for a multiplanar implant (p=0.008) were found to be statistically significant risk factors for nodal recurrence. Other factors like high-grade tumors, ulcero-infiltrative lesions, implant of mobile tongue, and low hemoglobin, though relevant, were not found to be statistically significant. CONCLUSIONS: We recommend prophylactic nodal irradiation in addition to brachytherapy even for early-stage oral cancers treated with interstitial brachytherapy. Furthermore, the invasive procedure of interstitial brachytherapy causing a disruption of body's physiologic barrier to localize the disease is itself a probable risk factor for late nodal recurrence. Whether this, apart from the poor prognostic factors, causes increased chance of spread of a localized disease needs to be evaluated by a large prospective randomized study. This is needed to find out exactly the scenario where exclusive brachytherapy will be appropriate for treatment of early-stage oral cavity cancers.