@article{ekelöf_garrard_judd_rosen_xie_kashuba_muddiman_2018, title={Evaluation of Digital Image Recognition Methods for Mass Spectrometry Imaging Data Analysis}, volume={29}, ISSN={1044-0305 1879-1123}, url={http://dx.doi.org/10.1007/S13361-018-2073-0}, DOI={10.1007/s13361-018-2073-0}, abstractNote={Analyzing mass spectrometry imaging data can be laborious and time consuming, and as the size and complexity of datasets grow, so does the need for robust automated processing methods. We here present a method for comprehensive, semi-targeted discovery of molecular distributions of interest from mass spectrometry imaging data, using widely available image similarity scoring algorithms to rank images by spatial correlation. A fast and powerful batch search method using a MATLAB implementation of structural similarity (SSIM) index scoring with a pre-selected reference distribution is demonstrated for two sample imaging datasets, a plant metabolite study using Artemisia annua leaf, and a drug distribution study using maraviroc-dosed macaque tissue. Graphical Abstract ᅟ.}, number={12}, journal={Journal of The American Society for Mass Spectrometry}, publisher={Springer Science and Business Media LLC}, author={Ekelöf, Måns and Garrard, Kenneth P. and Judd, Rika and Rosen, Elias P. and Xie, De-Yu and Kashuba, Angela D. M. and Muddiman, David C.}, year={2018}, month={Oct}, pages={2467–2470} }
 @article{rosen_bokhart_nazari_muddiman_2015, title={Influence of C-Trap Ion Accumulation Time on the Detectability of Analytes in IR-MALDESI MSI}, volume={87}, ISSN={["1520-6882"]}, DOI={10.1021/acs.analchem.5b02641}, abstractNote={Laser desorption followed by post electrospray ionization requires synchronized timing of the key events (sample desorption/ionization, mass spectrometry analysis, and sample translation) necessary to conduct mass spectrometry imaging (MSI) with adequate analyte sensitivity. In infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI) MSI analyses, two laser pulses are used for analysis at each volumetric element, or voxel, of a biological sample and ion accumulation in the C-trap exceeding 100 ms is necessary to capture all sample-associated ions using an infrared laser with a 20 Hz repetition rate. When coupled to an Orbitrap-based mass spectrometer like the Q Exactive Plus, this time window for ion accumulation exceeds dynamically controlled trapping of samples with comparable ion flux by Automatic Gain Control (AGC), which cannot be used during MSI analysis. In this work, a next-generation IR-MALDESI source has been designed and constructed that incorporates a mid-infrared OPO laser capable of operating at 100 Hz and allows requisite C-trap inject time during MSI to be reduced to 30 ms. Analyte detectability of the next-generation IR-MALDESI integrated source has been evaluated as a function of laser repetition rate (100-20 Hz) with corresponding C-trap ion accumulation times (30-110 ms) in both untargeted and targeted analysis of biological samples. Reducing the C-trap ion accumulation time resulted in increased ion abundance by up to 3 orders of magnitude for analytes ranging from xenobiotics to endogenous lipids, and facilitated the reduction of voxel-to-voxel variability by more than 3-fold.}, number={20}, journal={ANALYTICAL CHEMISTRY}, author={Rosen, Elias P. and Bokhart, Mark T. and Nazari, Milad and Muddiman, David C.}, year={2015}, month={Oct}, pages={10483–10490} }
 @article{rosen_bokhart_ghashghaei_muddiman_2015, title={Influence of Desorption Conditions on Analyte Sensitivity and Internal Energy in Discrete Tissue or Whole Body Imaging by IR-MALDESI}, volume={26}, ISSN={1044-0305 1879-1123}, url={http://dx.doi.org/10.1007/s13361-015-1114-1}, DOI={10.1007/s13361-015-1114-1}, abstractNote={Analyte signal in a laser desorption/postionization scheme such as infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI) is strongly coupled to the degree of overlap between the desorbed plume of neutral material from a sample and an orthogonal electrospray. In this work, we systematically examine the effect of desorption conditions on IR-MALDESI response to pharmaceutical drugs and endogenous lipids in biological tissue using a design of experiments approach. Optimized desorption conditions have then been used to conduct an untargeted lipidomic analysis of whole body sagittal sections of neonate mouse. IR-MALDESI response to a wide range of lipid classes has been demonstrated, with enhanced lipid coverage received by varying the laser wavelength used for mass spectrometry imaging (MSI). Targeted MS(2) imaging (MS(2)I) of an analyte, cocaine, deposited beneath whole body sections allowed determination of tissue-specific ion response factors, and CID fragments of cocaine were monitored to comment on wavelength-dependent internal energy deposition based on the "survival yield" method.}, number={6}, journal={Journal of The American Society for Mass Spectrometry}, publisher={Springer Science and Business Media LLC}, author={Rosen, Elias P. and Bokhart, Mark T. and Ghashghaei, H. Troy and Muddiman, David C.}, year={2015}, month={Apr}, pages={899–910} }
 @article{thompson_bokhart_sykes_adamson_fedoriw_luciw_muddiman_kashuba_rosen_2015, title={Mass Spectrometry Imaging Reveals Heterogeneous Efavirenz Distribution within Putative HIV Reservoirs}, volume={59}, ISSN={["1098-6596"]}, DOI={10.1128/aac.04952-14}, abstractNote={ABSTRACT
          Persistent HIV replication within active viral reservoirs may be caused by inadequate antiretroviral penetration. Here, we used mass spectrometry imaging with infrared matrix-assisted laser desorption–electrospray ionization to quantify the distribution of efavirenz within tissues from a macaque dosed orally to a steady state. Intratissue efavirenz distribution was heterogeneous, with the drug concentrating in the lamina propria of the colon, the primary follicles of lymph nodes, and the brain gray matter. These are the first imaging data of an antiretroviral drug in active viral reservoirs.}, number={5}, journal={ANTIMICROBIAL AGENTS AND CHEMOTHERAPY}, author={Thompson, Corbin G. and Bokhart, Mark T. and Sykes, Craig and Adamson, Lourdes and Fedoriw, Yuri and Luciw, Paul A. and Muddiman, David C. and Kashuba, Angela D. M. and Rosen, Elias P.}, year={2015}, month={May}, pages={2944–2948} }
 @article{bokhart_rosen_thompson_sykes_kashuba_muddiman_2015, title={Quantitative mass spectrometry imaging of emtricitabine in cervical tissue model using infrared matrix-assisted laser desorption electrospray ionization}, volume={407}, ISSN={["1618-2650"]}, DOI={10.1007/s00216-014-8220-y}, abstractNote={A quantitative mass spectrometry imaging (QMSI) technique using infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI) is demonstrated for the antiretroviral (ARV) drug emtricitabine in incubated human cervical tissue. Method development of the QMSI technique leads to a gain in sensitivity and removal of interferences for several ARV drugs. Analyte response was significantly improved by a detailed evaluation of several cationization agents. Increased sensitivity and removal of an isobaric interference was demonstrated with sodium chloride in the electrospray solvent. Voxel-to-voxel variability was improved for the MSI experiments by normalizing analyte abundance to a uniformly applied compound with similar characteristics to the drug of interest. Finally, emtricitabine was quantified in tissue with a calibration curve generated from the stable isotope-labeled analog of emtricitabine followed by cross-validation using liquid chromatography tandem mass spectrometry (LC-MS/MS). The quantitative IR-MALDESI analysis proved to be reproducible with an emtricitabine concentration of 17.2 ± 1.8 μg/gtissue. This amount corresponds to the detection of 7 fmol/voxel in the IR-MALDESI QMSI experiment. Adjacent tissue slices were analyzed using LC-MS/MS which resulted in an emtricitabine concentration of 28.4 ± 2.8 μg/gtissue.}, number={8}, journal={ANALYTICAL AND BIOANALYTICAL CHEMISTRY}, author={Bokhart, Mark T. and Rosen, Elias and Thompson, Corbin and Sykes, Craig and Kashuba, Angela D. M. and Muddiman, David C.}, year={2015}, month={Mar}, pages={2073–2084} }