2024
mTOR inhibition enhances synaptic and mitochondrial function in Alzheimer’s disease in an APOE genotype-dependent manner
Sanganahalli B, Mihailovic J, Vekaria H, Coman D, Yackzan A, Flemister A, Aware C, Wenger K, Hubbard W, Sullivan P, Hyder F, Lin A. mTOR inhibition enhances synaptic and mitochondrial function in Alzheimer’s disease in an APOE genotype-dependent manner. Cerebrovascular And Brain Metabolism Reviews 2024, 44: 1745-1758. PMID: 38879800, PMCID: PMC11494852, DOI: 10.1177/0271678x241261942.Peer-Reviewed Original ResearchResponse to rapamycinE3FAD miceMitochondrial functionAlzheimer's diseaseMammalian target of rapamycinAD genetic risk factorsApolipoprotein E4Neuronal mitochondrial functionMitochondrial oxidative metabolismE4FAD miceHuman APOE4 geneTCA cycle rateGenetic risk factorsGenotype-dependent mannerE3FADTarget of rapamycinAPOE4 geneAPOE3 alleleGlutamate-glutamine cycleAPOE4 carriersBioenergetic measurementsE4FADMetabolic functionsAPOE genotypeMammalian target of rapamycin inhibitionHigh‐resolution extracellular pH imaging of liver cancer with multiparametric MR using Deep Image Prior
Dong S, Shewarega A, Chapiro J, Cai Z, Hyder F, Coman D, Duncan J. High‐resolution extracellular pH imaging of liver cancer with multiparametric MR using Deep Image Prior. NMR In Biomedicine 2024, 37: e5145. PMID: 38488205, DOI: 10.1002/nbm.5145.Peer-Reviewed Original ResearchDeep Image PriorU-NetUnsupervised deep learning techniquesU-Net parametersDeep learning techniquesHigh-resolution ground truthU-Net architectureSuper-resolution imagingImage priorsSuper-resolutionGround truthMean absolute errorDeepSpatial resolutionPostprocessing methodDeep imagingAbsolute errorImagesAnatomical MR imagesMR spectroscopic imagingAnatomical informationSpectroscopic imagingInformationAcquisition timeErrorEffect of Incomplete Cryoablation and Matrix Metalloproteinase Inhibition on Intratumoral CD8+ T-Cell Infiltration in Murine Hepatocellular Carcinoma.
Shewarega A, Santana J, Nam D, Berz A, Tefera J, Kahl V, Mishra S, Coman D, Duncan J, Roberts S, Wetter A, Madoff D, Chapiro J. Effect of Incomplete Cryoablation and Matrix Metalloproteinase Inhibition on Intratumoral CD8+ T-Cell Infiltration in Murine Hepatocellular Carcinoma. Radiology 2024, 310: e232365. PMID: 38349244, PMCID: PMC10902598, DOI: 10.1148/radiol.232365.Peer-Reviewed Original ResearchConceptsT cell infiltrationCD8<sup>+</sup> T cellsMatrix metalloproteinase inhibitionT cellsHepatocellular carcinomaMatrix metalloproteinase inhibitorsMatrix metalloproteinasesResidual tumorCXCR3<sup>+</sup> CD8<sup>+</sup> T cellsCytotoxic CD8<sup>+</sup> T cell infiltrationIntratumoral CD8+ T cell infiltrationCD8+ T cell infiltrationCD8<sup>+</sup> T cell infiltrationMouse model of hepatocellular carcinomaEarly-stage hepatocellular carcinomaImage-guided tumor ablationUnpaired Student's <i>t</i> testModel of hepatocellular carcinomaFirst-line therapyMurine hepatocellular carcinomaT cell subsetsTumor-associated macrophagesMurine HCC modelLocal immune responseFemale BALB/c miceTransmembrane pH gradient imaging in rodent glioma models
Mishra S, Santana J, Mihailovic J, Hyder F, Coman D. Transmembrane pH gradient imaging in rodent glioma models. NMR In Biomedicine 2024, 37: e5102. PMID: 38263680, PMCID: PMC10987279, DOI: 10.1002/nbm.5102.Peer-Reviewed Original ResearchNormal tissuesRodent glioma modelsGL261 gliomasU87 gliomasTumor microenvironmentPotential therapeutic targetGlioma modelTumor survivalExtracellular acidosisTumorMetabolic reprogrammingRegulate drug deliveryIntracellular pHRat brainExtracellular pHTherapeutic targetGliomaMouse brainDrug deliveryIntracellular milieuTransmembrane pH gradientBrainSubmillimeter resolutionTissueCells
2023
Imaging the transmembrane pH gradient in gliomas
Mishra S, Mihailović J, Hyder F, Coman D. Imaging the transmembrane pH gradient in gliomas. Proceedings Of The International Society For Magnetic Resonance In Medicine ... Scientific Meeting And Exhibition. 2023 DOI: 10.58530/2023/3928.Peer-Reviewed Original ResearchAssess tumor aggressivenessMonitoring treatment efficacyTransmembrane pH gradientTumor responseTumor microenvironmentTumor aggressivenessRG2 tumorsLocal drug deliveryExtracellular acidosisTherapeutic outcomesTumorTreatment efficacyNormal tissuesBrain tumorsIntracellular pHExtracellular pHFunction biomarkersPositive therapeutic outcomesDrug deliveryIntracellular milieuBrainAcidosisGlioma
2022
White matter abnormalities in the Hdc knockout mouse, a model of tic and OCD pathophysiology
Jindachomthong K, Yang C, Huang Y, Coman D, Rapanelli M, Hyder F, Dougherty J, Frick L, Pittenger C. White matter abnormalities in the Hdc knockout mouse, a model of tic and OCD pathophysiology. Frontiers In Molecular Neuroscience 2022, 15: 1037481. PMID: 36504678, PMCID: PMC9731796, DOI: 10.3389/fnmol.2022.1037481.Peer-Reviewed Original ResearchTourette syndromeDiffusion tensor imagingDorsal striatumKnockout miceFractional anisotropyCortico-basal ganglia circuitryHDC knockout miceWhite matter abnormalitiesIntact mouse brainBiosynthesis of histamineCortical projectionsNeurochemical abnormalitiesPosterior hypothalamusKO miceVocal ticsFunctional abnormalitiesMyelin productionPathological alterationsDTI literatureOCD pathophysiologyMouse brainBrain regionsKO modelAbnormalitiesTensor imagingMR Imaging–Based In Vivo Macrophage Imaging to Monitor Immune Response after Radiofrequency Ablation of the Liver
Santana J, Petukhova-Greenstein A, Gross M, Hyder F, Pekurovsky V, Gottwald L, Boustani A, Walsh J, Kucukkaya A, Malpani R, Madoff D, Goldberg S, Ahmed M, Joshi N, Coman D, Chapiro J. MR Imaging–Based In Vivo Macrophage Imaging to Monitor Immune Response after Radiofrequency Ablation of the Liver. Journal Of Vascular And Interventional Radiology 2022, 34: 395-403.e5. PMID: 36423815, PMCID: PMC11042914, DOI: 10.1016/j.jvir.2022.11.013.Peer-Reviewed Original ResearchConceptsImmune responseT1-weighted MRPrussian blue stainingRadiofrequency ablationRF ablationC57BL/6 wild-type miceMR imagingDose-escalation studyLocal immune responseMass cytometryWild-type miceRadiological-pathological correlationBlue stainingT1-weighted MR imagingHepatic radiofrequency ablationCD68 antibodyUntreated lobeVivo doseHepatic RF ablationVivo macrophagesMacrophagesMiceMR imaging scannerCoagulation areaCD68Brain-targeting, acid-responsive antioxidant nanoparticles for stroke treatment and drug delivery
Zhang S, Peng B, Chen Z, Yu J, Deng G, Bao Y, Ma C, Du F, Sheu WC, Kimberly WT, Simard JM, Coman D, Chen Q, Hyder F, Zhou J, Sheth KN. Brain-targeting, acid-responsive antioxidant nanoparticles for stroke treatment and drug delivery. Bioactive Materials 2022, 16: 57-65. PMID: 35386312, PMCID: PMC8958421, DOI: 10.1016/j.bioactmat.2022.02.033.Peer-Reviewed Original ResearchDrug deliveryStroke treatmentTherapeutic agentsBetulinic acidNatural nanomaterialsSurface conjugationDrug releaseDrug carriersAntioxidant nanoparticlesEfficient carrierTreatment of strokeEffective pharmacological treatmentCause of deathNanoparticlesPotent therapeutic agentIschemic brainPharmacological treatmentCXCR4 antagonistIntravenous administrationSignificant efficacyIschemic tissueNeuroprotective peptidePotent antioxidantStrokeCarriersMethylated tetra‐amide derivatives of paramagnetic complexes for magnetic resonance biosensing with both BIRDS and CEST
Zakaria ABM, Huang Y, Coman D, Mishra SK, Mihailovic JM, Maritim S, Rojas‐Quijano F, Jurek P, Kiefer GE, Hyder F. Methylated tetra‐amide derivatives of paramagnetic complexes for magnetic resonance biosensing with both BIRDS and CEST. NMR In Biomedicine 2022, 35: e4687. PMID: 34970801, DOI: 10.1002/nbm.4687.Peer-Reviewed Original ResearchComparison of Lanthanide Macrocyclic Complexes as 23Na NMR Sensors
Khan MH, Mishra SK, Zakaria ABM, Mihailović J, Coman D, Hyder F. Comparison of Lanthanide Macrocyclic Complexes as 23Na NMR Sensors. Analytical Chemistry 2022, 94: 2536-2545. PMID: 35073049, DOI: 10.1021/acs.analchem.1c04432.Peer-Reviewed Original ResearchConceptsLanthanide macrocyclic complexesParamagnetic lanthanide ionsMagnetic resonance agentsLanthanide complexesMacrocyclic complexesMacrocyclic designDownfield shiftLanthanide ionsNa NMRBulk magnetic susceptibility effectsUnpaired electronChelating agentBiomedical applicationsNegative chargeNMR sensorSodium ionsTriazacyclononaneIonsComplexesBiological importanceMacrocyclicTmDOTPNaCationsGd
2021
High‐resolution pH imaging using ratiometric chemical exchange saturation transfer combined with biosensor imaging of redundant deviation in shifts featuring paramagnetic DOTA‐tetraglycinate agents
Mihailovic JM, Huang Y, Walsh JJ, Khan MH, Mishra SK, Samuels S, Hyder F, Coman D. High‐resolution pH imaging using ratiometric chemical exchange saturation transfer combined with biosensor imaging of redundant deviation in shifts featuring paramagnetic DOTA‐tetraglycinate agents. NMR In Biomedicine 2021, 35: e4658. PMID: 34837412, DOI: 10.1002/nbm.4658.Peer-Reviewed Original ResearchComparison of metabolic and immunologic responses to transarterial chemoembolization with different chemoembolic regimens in a rabbit VX2 liver tumor model
Doemel LA, Santana JG, Savic LJ, Gaupp FML, Borde T, Petukhova-Greenstein A, Kucukkaya AS, Schobert IT, Hamm CA, Gebauer B, Walsh JJ, Rexha I, Hyder F, Lin M, Madoff DC, Schlachter T, Chapiro J, Coman D. Comparison of metabolic and immunologic responses to transarterial chemoembolization with different chemoembolic regimens in a rabbit VX2 liver tumor model. European Radiology 2021, 32: 2437-2447. PMID: 34718844, PMCID: PMC9359419, DOI: 10.1007/s00330-021-08337-3.Peer-Reviewed Original ResearchConceptsDrug-eluting embolicsImmune cell infiltrationAntigen-presenting cellsBicarbonate infusionConventional TACEDEE-TACETransarterial chemotherapyCell infiltrationImmune cellsPeritumoral infiltrationT lymphocytesIntratumoral immune cell infiltrationTumor modelRabbit VX2 liver tumor modelImmunological tumor microenvironmentVX2 liver tumor modelIntra-arterial therapyIntra-arterial treatmentRabbit VX2 tumor modelLiver tumor modelTumor-bearing rabbitsVX2 tumor modelMann-Whitney U testIntratumoral presenceTransarterial chemoembolizationRenal plasticity revealed through reversal of polycystic kidney disease in mice
Dong K, Zhang C, Tian X, Coman D, Hyder F, Ma M, Somlo S. Renal plasticity revealed through reversal of polycystic kidney disease in mice. Nature Genetics 2021, 53: 1649-1663. PMID: 34635846, PMCID: PMC9278957, DOI: 10.1038/s41588-021-00946-4.Peer-Reviewed Original ResearchConceptsPKD genesAutosomal dominant polycystic kidney diseaseCyst cell proliferationGene functionPolycystic kidney diseaseCell shapeGenesKidney diseaseExtracellular matrix depositionCell proliferationKidney tubule cellsNormal lumensDominant polycystic kidney diseaseUnexpected capacityPhenotypic featuresCyst progressionMatrix depositionCellsPlasticityCyst formationCystic tubulesMyofibroblast activationProliferationSquamoid cellsKidney resultsImaging Hallmarks of the Tumor Microenvironment in Glioblastoma Progression
Walsh JJ, Parent M, Akif A, Adam LC, Maritim S, Mishra SK, Khan MH, Coman D, Hyder F. Imaging Hallmarks of the Tumor Microenvironment in Glioblastoma Progression. Frontiers In Oncology 2021, 11: 692650. PMID: 34513675, PMCID: PMC8426346, DOI: 10.3389/fonc.2021.692650.Peer-Reviewed Original ResearchImaging the transmembrane and transendothelial sodium gradients in gliomas
Khan MH, Walsh JJ, Mihailović JM, Mishra SK, Coman D, Hyder F. Imaging the transmembrane and transendothelial sodium gradients in gliomas. Scientific Reports 2021, 11: 6710. PMID: 33758290, PMCID: PMC7987982, DOI: 10.1038/s41598-021-85925-9.Peer-Reviewed Original ResearchImaging extracellular acidification and immune activation in cancer
Hyder F, Coman D. Imaging extracellular acidification and immune activation in cancer. Current Opinion In Biomedical Engineering 2021, 18: 100278. PMID: 33997581, PMCID: PMC8115219, DOI: 10.1016/j.cobme.2021.100278.Peer-Reviewed Original ResearchGene-centric viewMetabolic reprogrammingHostile ecosystemCancer hallmarksHabitat acidificationHost cellsFuture cancer therapyAerobic glycolysisDiverse mechanismsMetabolic interactionsExtracellular acidificationDifferent nutrientsCancer cellsImmune cellsDisease tissuesCellsTumor milieuNutrientsCancer therapyMetabolismRecent evidenceIncidental phenomenonAcidificationReprogrammingOncogene
2020
A high‐throughput imaging platform to characterize extracellular pH in organotypic three‐dimensional in vitro models of liver cancer
Savic LJ, Schobert IT, Hamm CA, Adam LC, Hyder F, Coman D. A high‐throughput imaging platform to characterize extracellular pH in organotypic three‐dimensional in vitro models of liver cancer. NMR In Biomedicine 2020, 34: e4465. PMID: 33354836, DOI: 10.1002/nbm.4465.Peer-Reviewed Original ResearchConceptsLiver cancer modelLiver cancerHepatocellular carcinomaCancer modelNon-tumorous hepatocytesUnpaired t-testCell linesDose-dependent mannerHepatocyte cell lineTreatment responseTherapy resistanceMagnetic resonance spectroscopicT MR scannerPersonalized treatmentTumor metabolismCancerTumor pHMR resultsT-testCarcinomaViability assaysExtracellular pHMR scannerANOVA testTreatmentTumor-targeted pH-low insertion peptide delivery of theranostic gadolinium nanoparticles for image-guided nanoparticle-enhanced radiation therapy
Liu W, Deacon J, Yan H, Sun B, Liu Y, Hegan D, Li Q, Coman D, Parent M, Hyder F, Roberts K, Nath R, Tillement O, Engelman D, Glazer P. Tumor-targeted pH-low insertion peptide delivery of theranostic gadolinium nanoparticles for image-guided nanoparticle-enhanced radiation therapy. Translational Oncology 2020, 13: 100839. PMID: 32763504, PMCID: PMC7408331, DOI: 10.1016/j.tranon.2020.100839.Peer-Reviewed Original ResearchHuman lung cancer cellsA549 human lung cancer cellsMolecular MRI techniqueTumor-bearing miceLung cancer cellsClonogenic survival assaysVivo radiosensitizationRadiation therapySolid tumorsTumor cell metabolismTumorsEnhanced radiosensitivityTumor cellsMR imagingSurvival assaysMRI techniquesCancer cellsTreatment planningRadiotherapyTumor coreGeneral hallmarkRadiotherapy treatment planningRadiosensitivityPeptide deliveryDeliveryMolecular MRI of the Immuno-Metabolic Interplay in a Rabbit Liver Tumor Model: A Biomarker for Resistance Mechanisms in Tumor-targeted Therapy?
Savic LJ, Doemel LA, Schobert IT, Montgomery RR, Joshi N, Walsh JJ, Santana J, Pekurovsky V, Zhang X, Lin M, Adam L, Boustani A, Duncan J, Leng L, Bucala RJ, Goldberg SN, Hyder F, Coman D, Chapiro J. Molecular MRI of the Immuno-Metabolic Interplay in a Rabbit Liver Tumor Model: A Biomarker for Resistance Mechanisms in Tumor-targeted Therapy? Radiology 2020, 296: 575-583. PMID: 32633675, PMCID: PMC7434651, DOI: 10.1148/radiol.2020200373.Peer-Reviewed Original ResearchConceptsImmuno-oncologic therapiesConventional transarterial chemoembolizationTransarterial chemoembolizationIntratumoral immune cell infiltrationMR spectroscopyRabbit liver tumor modelPrussian blue iron stainingAntigen-presenting immune cellsIntra-arterial infusionImmune cell infiltrationNew Zealand white rabbitsLiver tumor modelImmune cell exclusionLiver cancer modelContrast material administrationT2-weighted MRIZealand white rabbitsT2-weighted imagingResistance mechanismsImmunosuppressive tumorHLA-DRCell infiltrationImmune cellsImmunohistochemistry stainingRing enhancementMolecular Imaging of Extracellular Tumor pH to Reveal Effects of Locoregional Therapy on Liver Cancer Microenvironment
Savic LJ, Schobert I, Peters D, Walsh JJ, Laage-Gaupp F, Hamm CA, Tritz N, Doemel LA, Lin M, Sinusas A, Schlachter T, Duncan JS, Hyder F, Coman D, Chapiro J. Molecular Imaging of Extracellular Tumor pH to Reveal Effects of Locoregional Therapy on Liver Cancer Microenvironment. Clinical Cancer Research 2020, 26: 428-438. PMID: 31582517, PMCID: PMC7244230, DOI: 10.1158/1078-0432.ccr-19-1702.Peer-Reviewed Original ResearchConceptsMR spectroscopic imagingLocoregional therapyLiver cancer microenvironmentConventional transarterial chemoembolizationNew Zealand white rabbitsTumor pHMost liver tumorsZealand white rabbitsMolecular imaging paradigmsPositive therapeutic outcomesTumor residualsTransarterial chemoembolizationTumor devascularizationHistopathologic markersViable tumorSurrogate biomarkerLiver tumorsLiver cancerTumor enhancementLiver parenchymaMetabolic markersMultiparametric MRITherapeutic outcomesHIF-1αVX2 tumors