@article{bokhart_manni_garrard_ekelöf_nazari_muddiman_2017, title={IR-MALDESI Mass Spectrometry Imaging at 50 Micron Spatial Resolution}, volume={28}, ISSN={1044-0305 1879-1123}, url={http://dx.doi.org/10.1007/S13361-017-1740-X}, DOI={10.1007/s13361-017-1740-x}, abstractNote={High spatial resolution in mass spectrometry imaging (MSI) is crucial to understanding the biology dictated by molecular distributions in complex tissue systems. Here, we present MSI using infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI) at 50 μm resolution. An adjustable iris, beam expander, and an aspherical focusing lens were used to reduce tissue ablation diameters for MSI at high resolution. The laser beam caustic was modeled using laser ablation paper to calculate relevant laser beam characteristics. The minimum laser spot diameter on the tissue was determined using tissue staining and microscopy. Finally, the newly constructed optical system was used to image hen ovarian tissue with and without oversampling, detailing tissue features at 50 μm resolution. Graphical Abstract ᅟ.}, number={10}, journal={Journal of The American Society for Mass Spectrometry}, publisher={Springer Nature}, author={Bokhart, Mark T. and Manni, Jeffrey and Garrard, Kenneth P. and Ekelöf, Måns and Nazari, Milad and Muddiman, David C.}, year={2017}, month={Jul}, pages={2099–2107} }
 @article{rosen_thompson_bokhart_prince_sykes_muddiman_kashuba_2016, title={Analysis of Antiretrovirals in Single Hair Strands for Evaluation of Drug Adherence with Infrared-Matrix-Assisted Laser Desorption Electrospray Ionization Mass Spectrometry Imaging}, volume={88}, ISSN={["1520-6882"]}, DOI={10.1021/acs.analchem.5b03794}, abstractNote={Adherence to a drug regimen can be a strong predictor of health outcomes, and validated measures of adherence are necessary at all stages of therapy from drug development to prescription. Many of the existing metrics of drug adherence (e.g., self-report, pill counts, blood monitoring) have limitations, and analysis of hair strands has recently emerged as an objective alternative. Traditional methods of hair analysis based on LC-MS/MS (segmenting strands at ≥1 cm length) are not capable of preserving a temporal record of drug intake at higher resolution than approximately 1 month. Here, we evaluated the detectability of HIV antiretrovirals (ARVs) in hair from a range of drug classes using infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI) mass spectrometry imaging (MSI) with 100 μm resolution. Infrared laser desorption of hair strands was shown to penetrate into the strand cortex, allowing direct measurement by MSI without analyte extraction. Using optimized desorption conditions, a linear correlation between IR-MALDESI ion abundance and LC-MS/MS response was observed for six common ARVs with estimated limits of detection less than or equal to 1.6 ng/mg hair. The distribution of efavirenz (EFV) was then monitored in a series of hair strands collected from HIV infected, virologically suppressed patients. Because of the role hair melanin plays in accumulation of basic drugs (like most ARVs), an MSI method to quantify the melanin biomarker pyrrole-2,3,5-tricarboxylic acid (PTCA) was evaluated as a means of normalizing drug response between patients to develop broadly applicable adherence criteria.}, number={2}, journal={ANALYTICAL CHEMISTRY}, author={Rosen, Elias P. and Thompson, Corbin G. and Bokhart, Mark T. and Prince, Heather M. A. and Sykes, Craig and Muddiman, David C. and Kashuba, Angela D. M.}, year={2016}, month={Jan}, pages={1336–1344} }
 @misc{bokhart_muddiman_2016, title={Infrared matrix-assisted laser desorption electrospray ionization mass spectrometry imaging analysis of biospecimens}, volume={141}, ISSN={["1364-5528"]}, DOI={10.1039/c6an01189f}, abstractNote={Infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI) mass spectrometry imaging (MSI) is a versatile imaging technique capable of in-depth analysis for a wide variety of biospecimens.}, number={18}, journal={ANALYST}, author={Bokhart, M. T. and Muddiman, D. C.}, year={2016}, pages={5236–5245} }
 @article{nazari_bokhart_muddiman_2016, title={Whole-body mass spectrometry imaging by infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI)}, number={109}, journal={Jove-Journal of Visualized Experiments}, author={Nazari, M. and Bokhart, M. T. and Muddiman, D. C.}, year={2016} }
 @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 MS2 imaging (MS2I) 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} }
 @article{barry_robichaud_bokhart_thompson_sykes_kashuba_muddiman_2014, title={Mapping Antiretroviral Drugs in Tissue by IR-MALDESI MSI Coupled to the Q Exactive and Comparison with LC-MS/MS SRM Assay}, volume={25}, ISSN={["1879-1123"]}, DOI={10.1007/s13361-014-0884-1}, abstractNote={This work describes the coupling of the IR-MALDESI imaging source with the Q Exactive mass spectrometer. IR-MALDESI MSI was used to elucidate the spatial distribution of several HIV drugs in cervical tissues that had been incubated in either a low or high concentration. Serial sections of those analyzed by IR-MALDESI MSI were homogenized and analyzed by LC-MS/MS to quantify the amount of each drug present in the tissue. By comparing the two techniques, an agreement between the average intensities from the imaging experiment and the absolute quantities for each drug was observed. This correlation between these two techniques serves as a prerequisite to quantitative IR-MALDESI MSI. In addition, a targeted MS(2) imaging experiment was also conducted to demonstrate the capabilities of the Q Exactive and to highlight the added selectivity that can be obtained with SRM or MRM imaging experiments.}, number={12}, journal={JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY}, author={Barry, Jeremy A. and Robichaud, Guillaume and Bokhart, Mark T. and Thompson, Corbin and Sykes, Craig and Kashuba, Angela D. M. and Muddiman, David C.}, year={2014}, month={Dec}, pages={2038–2047} }