| 1. |
- Agarwal, Nisha Rani, 1987, et al.
(författare)
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Investigation of psoriasis skin tissue by label-free multi-modal imaging: a case study on a phototherapy-treated patient
- 2019
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Ingår i: Psoriasis: Targets and Therapy. - 2230-326X. ; 9, s. 43-57
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Tidskriftsartikel (refereegranskat)abstract
- Background: Psoriasis is a systemic inflammatory disease characterized by epidermal proliferation in the skin. Altered lipid metabolism is considered to be a central factor in the psoriatic etiopathogenesis. Thus, it is necessary to visualize chemical specificity of the samples for better medical diagnosis and treatment. Here, we investigate its role in the development of psoriatic lesions, before and after ultraviolet phototherapy, in a case study. Methods: The distribution and morphology of different lipids and fibrous proteins in psoriatic (lesional) tissues were visualized by two complementary label-free imaging techniques: 1) non-linear microscopy (NLM), providing images of lipids/proteins throughout the skin layers at submicrometer resolution; and 2) mass spectrometry imaging (MSI), offering high chemical specificity and hence the detection of different lipid species in the epidermal and dermal regions. A conventional method of histological evaluation was performed on the tissues, with no direct comparison with NLM and MSI. Results: Psoriatic tissues had a higher lipid content, mainly in cholesterol, in both the epidermal and dermal regions, compared to healthy tissues. Moreover, the collagen and elastin fibers in the psoriatic tissues had a tendency to assemble as larger bundles, while healthy tissues showed smaller fibers more homogeneously spread. Although phototherapy significantly reduced the cholesterol content, it also increased the amounts of collagen in both lesional and non-lesional tissues. Conclusion: This study introduces NLM and MSI as two complementary techniques which are chemical specific and can be used to assess and visualize the distribution of lipids, collagen, and elastin in a non-invasive and label-free manner.
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| 2. |
- Angerer, Tina B., 1987, et al.
(författare)
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Improved Molecular Imaging in Rodent Brain with Time-of-Flight-Secondary Ion Mass Spectrometry Using Gas Cluster Ion Beams and Reactive Vapor Exposure
- 2015
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Ingår i: Analytical Chemistry. - : American Chemical Society (ACS). - 0003-2700 .- 1520-6882. ; 87:8, s. 4305-4313
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Tidskriftsartikel (refereegranskat)abstract
- Imaging mass spectrometry has shown to be a valuable method in medical research and can be performed using different instrumentation and sample preparation methods, each one with specific advantages and drawbacks. Time-of-flight-secondary ion mass spectrometry (TOF-SIMS) has the advantage of high spatial resolution imaging but is often restricted to low mass molecular signals and can be very sensitive to sample preparation artifacts. In this report we demonstrate the advantages of using gas cluster ion beams (GCIBs) in combination with trifluoracetic acid (TFA) vapor exposure for the imaging of lipids in mouse brain sections. There is an optimum exposure to TFA that is beneficial for increasing high mass signal as well as producing signal from previously unobserved species in the mass spectrum. Cholesterol enrichment and crystallization on the sample surface is removed by TFA exposure uncovering a wider range of lipid species in the white matter regions of the tissue, greatly expanding the chemical coverage and the potential application of TOF-SIMS imaging in neurological studies. Ar-4000(+) (40 keV) in combination with TFA treatment facilitates high resolution, high mass imaging closing the gap between TOF-SIMS and matrix-assisted laser desorption ionization (MALDI).
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| 3. |
- Dowlatshahi Pour, Masoumeh, 1976, et al.
(författare)
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An investigation on the mechanism of sublimed DHB matrix on molecular ion yields in SIMS imaging of brain tissue
- 2016
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Ingår i: Analytical and Bioanalytical Chemistry. - : Springer Science and Business Media LLC. - 1618-2642 .- 1618-2650. ; 408:12, s. 3071-3081
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Tidskriftsartikel (refereegranskat)abstract
- We have characterized the use of sublimation to deposit matrix-assisted laser desorption/ionization (MALDI) matrices in secondary ion mass spectrometry (SIMS) analysis, i.e. matrix-enhanced SIMS (ME-SIMS), a common surface modification method to enhance sensitivity for larger molecules and to increase the production of intact molecular ions. We use sublimation to apply a thin layer of a conventional MALDI matrix, 2,5-dihydroxybenzoic acid (DHB), onto rat brain cerebellum tissue to show how this technique can be used to enhance molecular yields in SIMS while still retaining a lateral resolution around 2 mu m and also to investigate the mechanism of this enhancement. The results here illustrate that cholesterol, which is a dominant lipid species in the brain, is decreased on the tissue surface after deposition of matrix, particularly in white matter. The decrease of cholesterol is followed by an increased ion yield of several other lipid species. Depth profiling of the sublimed rat brain reveals that the lipid species are de facto extracted by the DHB matrix and concentrated in the top most layers of the sublimed matrix. This extraction/concentration of lipids directly leads to an increase of higher mass lipid ion yield. It is also possible that the decrease of cholesterol decreases the potential suppression of ion yield caused by cholesterol migration to the tissue surface. This result provides us with significant insights into the possible mechanisms involved when using sublimation to deposit this matrix in ME-SIMS.
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| 4. |
- Dowlatshahi Pour, Masoumeh, 1976, et al.
(författare)
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Food-induced changes of lipids in rat neuronal tissue visualized by ToF-SIMS imaging
- 2016
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Time of flight secondary ion mass spectrometry (ToF-SIMS) was used to image the lipid localization in brain tissue sections from rats fed specially processed cereals (SPC). An IonTof 5 instrument equipped with a Bi cluster ion gun was used to analyze the tissue sections. Data from 15 brain samples from control and cereal-fed rats were recorded and exported to principal components analysis (PCA). The data clearly show changes of certain lipids in the brain following cereal feeding. PCA score plots show a good separation in lipid distribution between the control and the SPC-fed group. The loadings plot reveal that the groups separated mainly due to changes in cholesterol, vitamin E and c18:2, c16:0 fatty acid distribution as well as some short chain monocarboxylic fatty acid compositions. These insights relate to the working mechanism of SPC as a dietary supplement. SPC is thought to activate antisecretory factor (AF), an endogenous protein with regulatory function for inflammation and fluid secretion. These data provide insights into lipid content in brain following SPC feeding and suggest a relation to activating AF.
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| 5. |
- Dowlatshahi Pour, Masoumeh, 1976, et al.
(författare)
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Mass spectrometric profiling of lipids in intestinal tissue from rats fed cereals processed for medical conditions
- 2016
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Ingår i: Biointerphases. - : American Vacuum Society. - 1934-8630 .- 1559-4106. ; 11:2, s. 1-7
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Tidskriftsartikel (refereegranskat)abstract
- Time-of-flight secondary ion mass spectrometry (ToF-SIMS) was used for lipid profiling of intestine tissue sections from rats fed specially processed cereals and rats fed ordinary feed as a control. This cereal is known to increase the activity of antisecretory factor in plasma and the exact mechanism for the activation process at the cellular level is unclear. ToF-SIMS has been used to track food induced changes in lipid content in intestinal tissue sections to gain insight into the possible mechanisms involved. Data from 20 intestine sections belonging to four different rats from each group of control and specially processed cereals-fed rats were obtained using the stage scan macroraster with a lateral resolution of 5 lm. Data were subsequently subjected to orthogonal partial least squares discriminant analysis. The data clearly show that changes of certain lipids are induced by the specially processed cereal feed. Scores plots show a well-defined separation between the two groups. The corresponding loading plots reveal that the groups separate mainly due to changes of vitamin E, phosphocholine, and phosphosphingolipid fragments, and that for the c18:2 fatty acid. The observed changes in lipids might give insight into the working mechanisms of antisecretory factor in the body, and this has been successfully used to understand the working mechanism of specially processed cereal-induced antisecretory factor activation in intestine.
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| 6. |
- Dowlatshahi Pour, Masoumeh, 1976, et al.
(författare)
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Mass spectrometry imaging as a novel approach to measure hippocampal zinc
- 2019
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Ingår i: Journal of Analytical Atomic Spectrometry. - : Royal Society of Chemistry (RSC). - 0267-9477 .- 1364-5544. ; 34:8, s. 1581-1587
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Tidskriftsartikel (refereegranskat)abstract
- Zinc (Zn2+) is an essential trace element that plays crucial roles in the functioning of hundreds of enzymes and DNA binding transcription factors. Zinc is also an essential neuromodulator and can act as a potent neurotoxin in excitotoxic brain injury after seizures, strokes, and brain trauma where high levels of Zn2+ can cause irreparable brain damage in certain brain regions. However, the mechanism of neurotoxicity has not been fully understood yet and is still under debate. In the present study, we have developed a time of flight secondary ion mass spectrometry (ToF-SIMS) imaging method to investigate the distribution of zinc in the rat brain. The zinc distribution in hippocampus sections from healthy rats and rats exposed to traumatic brain injury was imaged and the results were compared to those from conventional zinc-probe based fluorescence microscopy. Two related zinc species, ZnOH3 + and ZnO2H+, can successfully be visualized by ToF-SIMS in the rat hippocampus. Statistical data analysis of the image data demonstrated a substantial increase of both ZnOH3 + and ZnO2H+ in the zinc related species in the acute brain injury tissue. Our findings positively support the fact that toxic vesicular zinc accumulation might not be the sole source for neuronal degeneration following traumatic brain injuries. Also, we could successfully apply ToF-SIMS imaging for the first time to visualize the zinc content and distribution across hippocampus sections. Consequently, ToF-SIMS is a powerful method to further investigate biological phenomena such as seizures, ischemia, and strokes and also other forms of cellular damage in the central nervous system.
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| 7. |
- Dowlatshahi Pour, Masoumeh, 1976
(författare)
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Spatial analysis of lipids in tissue samples applying mass spectrometry imaging
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Lipids are important naturally occurring components in all living cellular organisms. They serve as the main building blocks of cellular membranes, participate in many signaling pathways and are also stored as an energy source. Due to the extreme complex cellular chemistry and structure of lipids, there is a real need to have a label-free technique with high chemical specificity, high accuracy and high sensitivity for study of lipids within the cell membrane. Mass spectrometry imaging (MSI) is capable of providing information on the chemical composition and spatial distribution of complex biological molecules. MSI is a powerful label-free tool for lipid analysis across biological materials. Both matrix-assisted laser desorption/ionization (MALDI) and secondary ion mass spectrometry (SIMS), the two most common MSI techniques, have recently undergone many developments to improve spatial resolution and provide high sensitivity, mainly for higher mass species. These two techniques offer different capabilities in the analysis of a biological system. The main differences are that larger molecules can be ionized and detected using MALDI, whereas SIMS is capable of detecting mainly small molecules but at higher spatial resolution compared to MALDI. This thesis mainly focuses on two scopes of investigation with different sample modifications and also on the overall applicability of MSI for analysis of tissue samples. In recent years, some surface modifications have been developed to enhance the yield of intact molecular species in SIMS. One of them is matrix enhancement secondary ion mass spectrometry (ME-SIMS), which is the combination of the protocol for MALDI sample preparation and normal SIMS. In paper I, the possible mechanism of the signal enhancement in ME-SIMS was studied. Here, sublimation was used to deposit a thin layer of an organic matrix on the surface of a brain tissue slice analyzed with SIMS. In this work, I showed that sublimation could successfully provide enhancement in ion yields for a multitude of lipid species in SIMS. The mechanism of this enhancement could be due to a lower ion suppression followed by removal of the cholesterol crystals from the surface of sample allowing detection for less abundant species. It is also possible that the extraction of some specific lipids into the deposited matrix directly leads to an increase of higher mass lipid ion yield. In paper II, two different surface modifications, including matrix sublimation and nanoparticle deposition were applied on Drosophila brain samples and lipid information obtained from MALDI analysis were compared. Here, it was shown that each technique can be used in a complementary approach to detect a variety of lipid species. In paper III, SIMS imaging was employed to investigate the effect of specially processed cereals, as a specific diet on the alteration of lipid composition across the rodent intestine tissue. In paper IV, I continued the study of changes in lipid content, this time on brain samples of animals exposed to the same diet. Intake of such cereals increases active antisecretory factor (AF) in plasma, an endogenous protein with proven regulatory function on inflammation and fluid secretion. Although, the exact mechanism for the activation process of AF at the cellular level remains unclear. The results show changes in lipid content of cell membrane in response to this cereals intake suggesting a relation to activating AF. In paper V, the techniques for developing of sample preparation in SIMS imaging were investigated to improve the signal intensity of intact molecules at higher resolution.
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| 8. |
- Hagvall, Lina, 1978, et al.
(författare)
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Skin permeation of nickel, cobalt and chromium salts in ex vivo human skin, visualized using mass spectrometry imaging
- 2021
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Ingår i: Toxicology in Vitro. - : Elsevier BV. - 0887-2333 .- 1879-3177. ; 76
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Tidskriftsartikel (refereegranskat)abstract
- Skin permeation and distribution of three of the most common skin sensitizers was investigated using a previously developed animal-free exposure method combined with imaging mass spectrometry. Nickel, cobalt, and chromium (III) salts were dissolved in a buffer and exposed to human skin ex vivo, to be analyzed using time of flight secondary ion mass spectrometry (ToF-SIMS). Our findings demonstrate that metal haptens mainly accumulated in the stratum corneum, however all three metal sensitizers could also be detected in the epidermis. Cobalt and chromium (III) species penetrated into the epidermis to a larger extent than nickel species. The degree of penetration into the epidermis is suggested to be affected by the sensitization potency of the metal salts, as well as their speciation, i.e. the amount of the respective metal present in the solution as bioaccessible and solubilised ions. Our method provided permeation profiles in human skin for known sensitizers, on a level of detail that is not possible to achieve by other means. The findings show that the permeation profiles are different, despite these sensitizers being all metal ions and common causes of contact allergy. Studying skin uptake by only considering penetration through the skin might therefore not give accurate results.
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| 9. |
- Hagvall, Lina, 1978, et al.
(författare)
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Skin permeation studies of chromium species-Evaluation of a reconstructed human epidermis model
- 2023
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Ingår i: Toxicology in Vitro. - 0887-2333 .- 1879-3177. ; 91
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Tidskriftsartikel (refereegranskat)abstract
- A reconstructed human epidermis (RHE) model, the EpiDerm, was investigated and compared to human skin ex vivo regarding tissue penetration and distribution of two chromium species, relevant in both occupational and general exposure in the population. Imaging mass spectrometry was used in analysis of the sectioned tissue. The RHE model gave similar results compared to human skin ex vivo for skin penetration of CrVI. However, the penetration of CrIII into the tissue of the RHE model compared to human skin ex vivo differed markedly, such that in the RHE model the CrIII species accumulated in the tissue layer corresponding to stratum corneum whereas in human skin ex vivo, the CrIII species penetrated evenly through the skin tissue. Further, skin lipids such as cholesterol were less abundant in the RHE model compared to the human skin tissue. Results presented here indicate that the RHE models do not possess the same fundamental properties as human skin tissue. As the RHE models appear to be able to give false negative results, experiments using RHE models for the study of skin penetration should be evaluated with caution.
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| 10. |
- Phan, Nhu TN, 1981, et al.
(författare)
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Laser Desorption Ionization Mass Spectrometry Imaging of Drosophila Brain Using Matrix Sublimation versus Modification with Nanoparticles
- 2016
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Ingår i: Analytical Chemistry. - : American Chemical Society (ACS). - 0003-2700 .- 1520-6882. ; 88:3, s. 1734-1741
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Tidskriftsartikel (refereegranskat)abstract
- Laser desorption ionization mass spectrometry (LDI-MS) is used to image brain lipids in the fruit fly, Drosophila, a common invertebrate model organism in biological and neurological studies. Three different sample preparation methods, including sublimation with two common organic matrixes for matrix-assisted laser desorption ionization (MALDI) and surface assisted laser desorption ionization (SALDI) using gold nano particles, are examined for sample profiling and imaging the fly brain. Recrystallization with trifluoroacetic acid following matrix deposition in MALDI is shown to increase the incorporation of biomolecules with one matrix, resulting in more efficient ionization, but not for the other matrix. The key finding here is that the mass fragments observed for the fly brain slices with different surface modifications are significantly different. Thus, these approaches can be combined to provide complementary analysis of chemical composition, particularly for the small metabolites, diacylglycerides, phosphatidylcholines, and triacylglycerides, in the fly brain. Furthermore, imaging appears to be beneficial using modification with gold nanoparticles in place of matrix in this application showing its potential for cellular and subcellular imaging. The imaging protocol developed here with both MALDI and SALDI provides the best and most diverse lipid chemical images of the fly brain to date with LDI.
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