In vivo magnetic resonance methods in pharmaceutical research: current status and perspectives

In the last decade, in vivo MR methods have become established tools in the drug discovery and development process. In this review, several successful and potential applications of MRI and MRS in stroke, rheumatoid and osteo‐arthritis, oncology and cardiovascular disorders are dealt with in detail. The versatility of the MR approach, allowing the study of various pathophysiological aspects in these disorders, is emphasized. New indication areas, for the characterization of which MR methods have hardly been used up to now, such as respiratory, gastro‐intestinal and skin diseases, are outlined in a subsequent section. A strength of MRI, being a non‐invasive imaging modality, is the ability to provide functional, i.e. physiological, readouts. Functional MRI examples discussed are the analysis of heart wall motion, perfusion MRI, tracer uptake and clearance studies, and neuronal activation studies. Functional information may also be derived from experiments using target‐specific contrast agents, which will become important tools in future MRI applications. Finally the role of MRI and MRS for characterization of transgenic and knock‐out animals, which have become a key technology in modern pharmaceutical research, is discussed. The advantages of MRI and MRS are versatility, allowing a comprehensive characterization of a diseased state and of the drug intervention, and non‐invasiveness, which is of relevance from a statistical, economical and animal welfare point of view. Successful applications in drug discovery exploit one or several of these aspects. In addition, the link between preclinical and clinical studies makes in vivo MR methods highly attractive methods for pharmaceutical research. Copyright © 1999 John Wiley & Sons, Ltd.

[1]  L. Hue,et al.  Protection against ischemic injury by nonvasoactive concentrations of nitric oxide synthase inhibitors in the perfused rabbit heart. , 1995, Circulation.

[2]  P. Lauterbur,et al.  Image Formation by Induced Local Interactions: Examples Employing Nuclear Magnetic Resonance , 1973, Nature.

[3]  P. Boesiger,et al.  Evaluation of Delayed Gastric Emptying in Diabetic Patients With Autonomic Neuropathy by a New Magnetic Resonance Imaging Technique and Radio-Opaque Markers , 1996, Diabetes Care.

[4]  K. Hossmann,et al.  Inhibition of Nonselective Cation Channels Reduces Focal Ischemic Injury of Rat Brain , 1997, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[5]  E. McVeigh,et al.  Techniques for high‐speed cardiac magnetic resonance imaging in rats and rabbits , 1997, Magnetic resonance in medicine.

[6]  S. Whitebread,et al.  Left ventricular wall stress and sarcoplasmic reticulum Ca(2+)-ATPase gene expression in renal hypertensive rats: dose-dependent effects of ACE inhibition and AT1-receptor blockade. , 1996, Cardiovascular research.

[7]  B. Rosen,et al.  Dynamic imaging with lanthanide chelates in normal brain: Contrast due to magnetic susceptibility effects , 1988, Magnetic resonance in medicine.

[8]  Mathias Hoehn-Berlage,et al.  Potassium-Induced Cortical Spreading Depressions during Focal Cerebral Ischemia in Rats: Contribution to Lesion Growth Assessed by Diffusion-Weighted NMR and Biochemical Imaging , 1996, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[9]  R S Balaban,et al.  Analysis of water‐macromolecule proton magnetization transfer in articular cartilage , 1993, Magnetic resonance in medicine.

[10]  D. Ingber,et al.  Metabolism of tumor regression from angiogenesis inhibition: 31P magnetic resonance spectroscopy , 1989, Magnetic resonance in medicine.

[11]  F. Wehrli,et al.  In vivo MR microscopy of the human skin , 1997, Magnetic resonance in medicine.

[12]  A. Sherry,et al.  Substrate selection early after reperfusion of ischemic regions in the working rabbit heart , 1996, Magnetic Resonance in Medicine.

[13]  C. Higgins,et al.  Assessment of severity of experimental pulmonary edema with magnetic resonance imaging. Effect of relaxation enhancement by Gd-DTPA. , 1985, Investigative radiology.

[14]  G. McCarthy,et al.  Echo-planar magnetic resonance imaging studies of frontal cortex activation during word generation in humans. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[15]  C. Jack,et al.  New technical developments in magnetic resonance imaging of epilepsy. , 1995, Magnetic resonance imaging.

[16]  Progression of a focal ischemic lesion in rat brain during treatment with a novel glycine/nmda antagonist: An in vivo three‐dimensional diffusion‐weighted MR microscopy study , 1997, Journal of magnetic resonance imaging : JMRI.

[17]  H. D'Arceuil,et al.  Recovery of apparent diffusion coefficient after ischemia-induced spreading depression relates to cerebral perfusion gradient. , 1996, Stroke.

[18]  A. Young,et al.  Three‐Dimensional Left Ventricular Deformation in Hypertrophic Cardiomyopathy , 1994, Circulation.

[19]  J. Kucharczyk,et al.  Nicardipine reduces ischemic brain injury. Magnetic resonance imaging/spectroscopy study in cats. , 1989, Stroke.

[20]  H C Charles,et al.  Human lung air spaces: potential for MR imaging with hyperpolarized He-3. , 1996, Radiology.

[21]  R. Turner,et al.  Dynamic magnetic resonance imaging of human brain activity during primary sensory stimulation. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[22]  A. Zemtsov,et al.  Human in vivo 31P spectroscopy of skin: potentially a powerful tool for noninvasive study of metabolism in a cutaneous tissue. , 1989, The Journal of dermatologic surgery and oncology.

[23]  G. Fagg,et al.  The competitive NMDA receptor antagonist CGP 40116 is a potent neuroprotectant in a rat model of focal cerebral ischemia. , 1994, Journal of neural transmission. Supplementum.

[24]  R. Herfkens,et al.  Ultrafast contrast enhanced magnetic resonance imaging of congenital hydronephrosis in a rat model. , 1994, The Journal of urology.

[25]  F. Buonanno,et al.  Proton NMR imaging in experimental ischemic infarction. , 1983, Stroke.

[26]  W. Manning,et al.  Measurement of left ventricular mass in rats using electrocardiogram-gated magnetic resonance imaging. , 1990, The American journal of physiology.

[27]  K. Hossmann,et al.  A modified rat model of middle cerebral artery thread occlusion under electrophysiological control for magnetic resonance investigations. , 1995, Magnetic resonance imaging.

[28]  L. Hedlund,et al.  Mechanism of Detection of Acute Cerebral Ischemia in Rats by Diffusion‐Weighted Magnetic Resonance Microscopy , 1992, Stroke.

[29]  M E Moseley,et al.  Assessment of myocardial salvage after ischemia and reperfusion using magnetic resonance imaging and spectroscopy. , 1989, Circulation.

[30]  Y. Kiyota,et al.  Beneficial effect of CV-4151 (Isbogrel), a thromboxane A2 synthase inhibitor, in a rat middle cerebral artery thrombosis model. , 1995, Thrombosis research.

[31]  W. Schwizer,et al.  Gd‐DOTA as a gastrointestinal contrast agent for gastric emptying measurements with MRI , 1994, Magnetic resonance in medicine.

[32]  P. Renshaw,et al.  Immunospecific NMR contrast agents. , 1986, Magnetic resonance imaging.

[33]  H. Iro,et al.  [Imaging superficial skin tumors of the ENT area. High frequency ultrasound in comparison with computerized tomography and magnetic resonance tomography]. , 1995, HNO.

[34]  P. Barker,et al.  Tumor trapping of 5-fluorouracil: in vivo 19F NMR spectroscopic pharmacokinetics in tumor-bearing humans and rabbits. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[35]  C. Sotak,et al.  Effects of a novel NMDA antagonist on experimental stroke rapidly and quantitatively assessed by diffusion‐weighted MRI , 1993, Neurology.

[36]  David G. Norris,et al.  Evolution of Regional Changes in Apparent Diffusion Coefficient during Focal Ischemia of Rat Brain: The Relationship of Quantitative Diffusion NMR Imaging to Reduction in Cerebral Blood Flow and Metabolic Disturbances , 1995, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[37]  R. Herfkens,et al.  Altered phosphate metabolism in myocardial infarction: P-31 MR spectroscopy. , 1987, Radiology.

[38]  J. Ingwall,et al.  Intracellular high-energy phosphate transfer in normal and hypertrophied myocardium. , 1987, Circulation.

[39]  I. Benjamin,et al.  Cardioprotective effects of 70-kDa heat shock protein in transgenic mice. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[40]  K. Nicolay,et al.  Contrast-enhanced dynamic magnetic resonance imaging of the rat kidney. , 1996, Journal of the American Society of Nephrology : JASN.

[41]  C M Kramer,et al.  Usefulness of magnetic resonance imaging early after acute myocardial infarction. , 1997, The American journal of cardiology.

[42]  J. Griffiths,et al.  In vivo detection of ifosfamide by 31P-MRS in rat tumours: increased uptake and cytotoxicity induced by carbogen breathing in GH3 prolactinomas. , 1997, British Journal of Cancer.

[43]  K. Petersen,et al.  Mechanism of impaired insulin-stimulated muscle glucose metabolism in subjects with insulin-dependent diabetes mellitus. , 1997, The Journal of clinical investigation.

[44]  J. Mintorovitch,et al.  Diffusion-weighted magnetic resonance imaging during brief focal cerebral ischemia and early reperfusion: evolution of delayed infarction in rats. , 1995, Neurological research.

[45]  R. Weissleder,et al.  Polymeric contrast agents for MR imaging of adrenal glands , 1993, Journal of magnetic resonance imaging : JMRI.

[46]  L. Nathanson,et al.  Prognosis and staging in melanoma. , 1996, Seminars in oncology.

[47]  D. Burstein,et al.  Gd‐DTPA2− as a measure of cartilage degradation , 1996, Magnetic resonance in medicine.

[48]  J. Elsen,et al.  Synteny conservation between parts of human chromosome 4q and bovine and ovine chromosomes 6. , 1996, Cytogenetics and Cell Genetics.

[49]  R. Kauppinen,et al.  Cerebral Energy Metabolism and Immediate Early Gene Induction Following Severe Incomplete Ischaemia in Transgenic Mice Overexpressing the Human Ornithine Decarboxylase Gene: Evidence that Putrescine is not Neurotoxic In Vivo , 1995, The European journal of neuroscience.

[50]  A. Fischman,et al.  Polyclonal human immunoglobulin G labeled with polymeric iron oxide: antibody MR imaging. , 1991, Radiology.

[51]  J. Seelig,et al.  Absolute quantification of the hepatic glycogen content in a patient with glycogen storage disease by 13C magnetic resonance spectroscopy. , 1996, Magnetic resonance imaging.

[52]  C. Sotak,et al.  The role of spreading depression in focal ischemia evaluated bv dffusion mapping , 1996, Annals of neurology.

[53]  R. Ordidge,et al.  Natural abundance 13C NMR spectrum of glycogen in humans , 1987, Magnetic resonance in medicine.

[54]  M Hoehn-Berlage,et al.  Relationship between diffusion-weighted MR images, cerebral blood flow, and energy state in experimental brain infarction. , 1995, Magnetic resonance imaging.

[55]  K. Uğurbil,et al.  Detection of 13C‐labeled metabolites in the in vivo canine heart by B1 insensitive heteronuclear coherent polarization transfer and comparison of signal enhancement with NOE , 1997, Magnetic resonance in medicine.

[56]  K Ugurbil,et al.  Functional magnetic resonance imaging of Broca's area during internal speech. , 1993, Neuroreport.

[57]  J. Ford,et al.  Nuclear magnetic resonance evaluation of stroke. A preliminary report. , 1983, Radiology.

[58]  V. Runge,et al.  Detectability of Early Brain Meningitis with Magnetic Resonance Imaging , 1995, Investigative radiology.

[59]  P. Morris,et al.  Ca2+ transient, Mg2+, and pH measurements in the cardiac cycle by 19F NMR. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[60]  T. Hammeke,et al.  Functional Magnetic Resonance Imaging in Partial Epilepsy , 1994, Epilepsia.

[61]  A. N. Stevens,et al.  NMR Studies of metabolites in living tissue , 1982 .

[62]  Y. Ohta,et al.  Studies on disease-modifying antirheumatic drugs: synthesis of novel quinoline and quinazoline derivatives and their anti-inflammatory effect. , 1996, Journal of medicinal chemistry.

[63]  E. Lo,et al.  Pharmacologic Reversal of Acute Changes in Diffusion-Weighted Magnetic Resonance Imaging in Focal Cerebral Ischemia , 1994, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[64]  N. van Bruggen,et al.  Assessing tumor angiogenesis using macromolecular MR imaging contrast media , 1997, Journal of magnetic resonance imaging : JMRI.

[65]  R R Edelman,et al.  Time course of the apparent diffusion coefficient (ADC) abnormality in human stroke , 1997, Neurology.

[66]  B. Ross,et al.  Morphologic effects of hGRH gene expression on the pituitary, liver, and pancreas of MT-hGRH transgenic mice. An in situ hybridization analysis. , 1992, The American journal of pathology.

[67]  M. Chopp,et al.  Dose-dependent metabolic response of mammary carcinoma to photodynamic therapy. , 1990, Radiation research.

[68]  A Potthast,et al.  Normal and abnormal pulmonary ventilation: visualization at hyperpolarized He-3 MR imaging. , 1996, Radiology.

[69]  R. Dijkhuizen,et al.  T1 and T2 relaxation times of the major 1H‐containing metabolites in rat brain after focal ischemia , 1995, NMR in biomedicine.

[70]  M. Rudin,et al.  Spirapril and cilazapril inhibit neointimal lesion development but cause no detectable inhibition of lumen narrowing after carotid artery balloon catheter injury in the rat. , 1993, Blood pressure.

[71]  D. Burstein,et al.  Diffusion of small solutes in cartilage as measured by nuclear magnetic resonance (NMR) spectroscopy and imaging , 1993, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[72]  M. Rudin,et al.  Noninvasive 3D MR microscopy as a tool in pharmacological research: application to a model of rheumatoid arthritis. , 1995, Magnetic resonance imaging.

[73]  L. Sokoloff,et al.  Measurement of local cerebral blood flow with iodo [14C] antipyrine. , 1978, The American journal of physiology.

[74]  N. Müller,et al.  Magnetic resonance imaging of hydrostatic pulmonary edema in isolated dog lungs: comparison with computed tomography. , 1990, Canadian Association of Radiologists journal = Journal l'Association canadienne des radiologistes.

[75]  R. Hof,et al.  Effect of Spirapril on Left Ventricular Hypertrophy Due to Volume Overload in Rats , 1992, Journal of cardiovascular pharmacology.

[76]  M. Chopp,et al.  A New Rat Model of Thrombotic Focal Cerebral Ischemia , 1997, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[77]  P. Ros,et al.  High-density oral barium sulfate in abdominal MRI: efficacy and tolerance in a clinical setting. , 1997, Magnetic resonance imaging.

[78]  J M Pauly,et al.  Lung parenchyma: projection reconstruction MR imaging. , 1991, Radiology.

[79]  M Hoehn-Berlage,et al.  Ultrafast Perfusion‐Weighted MRI of Functional Brain Activation in Rats During Forepaw Stimulation: Comparison with T*2‐Weighted MRI , 1996, NMR in biomedicine.

[80]  J. Griffiths,et al.  Fluorine- 19 F NMR Spectroscopy and Imaging In-Vivo , 1992 .

[81]  E E de Lange,et al.  MR imaging and spectroscopy using hyperpolarized 129Xe gas: Preliminary human results , 1997, Magnetic resonance in medicine.

[82]  M E Moseley,et al.  Comparison of diffusion‐ and T2‐weighted MRI for the early detection of cerebral ischemia and reperfusion in rats , 1991, Magnetic resonance in medicine.

[83]  B. Siewert,et al.  Acute human stroke studied by whole brain echo planar diffusion‐weighted magnetic resonance imaging , 1995, Annals of neurology.

[84]  J. Helpern,et al.  Diffusion-weighted imaging in epilepsy. , 1995, Magnetic resonance imaging.

[85]  M. Rudin,et al.  Treatment of hypertension with isradipine reduces infarct size following stroke in laboratory animals. , 1989, The American journal of medicine.

[86]  W. J. Lorenz,et al.  Real-time follow-up of 5-fluorouracil metabolism in the liver of tumor patients by means of F-19 MR spectroscopy. , 1990, Radiology.

[87]  P. Allegrini,et al.  The Competitive NMDA Antagonist CGP 40116 Permanently Reduces Brain Damage after Middle Cerebral Artery Occlusion in Rats , 1995, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[88]  A. Czurkó,et al.  Reconstruction of GABAergic Transmission and Behavior by Striatal Cell Grafts in Rats with Ischemic Infarcts in the Middle Cerebral Artery , 1993, Journal of neural transplantation & plasticity.

[89]  P Boesiger,et al.  Evaluation of Left Ventricular Segmental Wall Motion in Hypertrophic Cardiomyopathy With Myocardial Tagging , 1992, Circulation.

[90]  N. Beckmann,et al.  Effects of Sandimmune neoral on collagen-induced arthritis in DA rats: characterization by high resolution three-dimensional magnetic resonance imaging and by histology. , 1998, Journal of magnetic resonance.

[91]  P. Okunieff,et al.  Angiogenesis determines blood flow, metabolism, growth rate, and ATPase kinetics of tumors growing in an irradiated bed: 31P and 2H nuclear magnetic resonance studies. , 1991, Cancer research.

[92]  D. Louis Collins,et al.  Accurate, noninvasive diagnosis of human brain tumors by using proton magnetic resonance spectroscopy , 1996, Nature Medicine.

[93]  R. Kauppinen,et al.  Brain metabolites as 1H NMR markers of neuronal and glial disorders , 1989, NMR in biomedicine.

[94]  E. McVeigh MRI of myocardial function: motion tracking techniques. , 1996, Magnetic resonance imaging.

[95]  J. Kucharczyk,et al.  Magnetic resonance imaging of diffusion and perfusion , 1991, Topics in magnetic resonance imaging : TMRI.

[96]  M. Peterson,et al.  Persistent cardiovascular and behavioral nociceptive responses to subcutaneous formalin require peripheral nerve input , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[97]  K. Rootwelt,et al.  Gadodiamide in renal transplant patients: effects on renal function and usefulness as a glomerular filtration rate marker. , 1996, Nephron.

[98]  R Beyar,et al.  Magnetic Resonance Imaging as a Noninvasive Standard for the Quantitative Evaluation of Left Ventricular Mass, Ischemia, and Infarction a , 1990, Annals of the New York Academy of Sciences.

[99]  M. Rudin,et al.  Calcineurin inhibitors FK506 and SDZ ASM 981 alleviate the outcome of focal cerebral ischemic/reperfusion injury. , 1999, The Journal of pharmacology and experimental therapeutics.

[100]  S. Cohen,et al.  Comparison of the effects of new specific azasteroid inhibitors of steroid 5α‐reductase on canine hyperplastic prostate: Suppression of prostatic DHT correlated with prostate regression , 1995, The Prostate.

[101]  J R Griffiths,et al.  Classification of tumour 1H NMR spectra by pattern recognition , 1992, NMR in biomedicine.

[102]  M W Weiner,et al.  Mapping of lactate and N-acetyl-L-aspartate predicts infarction during acute focal ischemia: in vivo 1H magnetic resonance spectroscopy in rats. , 1996, Neurosurgery.

[103]  L. Vargova,et al.  Dynamic changes in water ADC, energy metabolism, extracellular space volume, and tortuosity in neonatal rat brain during global ischemia , 1996, Magnetic resonance in medicine.

[104]  In vivo NMR in pharmaceutical research. , 1992, Magnetic resonance imaging.

[105]  T. Budinger,et al.  Measurement of 129Xe T1 in Blood to Explore the Feasibility of Hyperpolarized 129Xe MRI , 1995, Journal of computer assisted tomography.

[106]  J Diskin,et al.  Magnetic resonance renography: optimisation of pulse sequence parameters and Gd-DTPA dose, and comparison with radionuclide renography. , 1997, Magnetic resonance imaging.

[107]  R. Coburn,et al.  Smooth muscle stretch-activated phospholipase C activity. , 1995, The American journal of physiology.

[108]  A. A. Spector,et al.  Cytotoxic effect of cis-parinaric acid in cultured malignant cells. , 1991, Cancer research.

[109]  T J Brady,et al.  Antimyosin-labeled monocrystalline iron oxide allows detection of myocardial infarct: MR antibody imaging. , 1992, Radiology.

[110]  Helen D'Arceuil,et al.  MR Detection of Cortical Spreading Depression Immediately after Focal Ischemia in the Rat , 1996, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[111]  L W Hedlund,et al.  Dynamics of magnetization in hyperpolarized gas MRI of the lung , 1997, Magnetic resonance in medicine.

[112]  J. Ackerman,et al.  In vivo NMR imaging and spectroscopic investigation of renal pathology in lean and obese rat kidneys , 1993, Magnetic resonance in medicine.

[113]  R. Gonzalez Molecular and Functional Magnetic Resonance Neuroimaging for the Study of Dementia a , 1996 .

[114]  B R Rosen,et al.  Detection of dopaminergic neurotransmitter activity using pharmacologic MRI: Correlation with PET, microdialysis, and behavioral data , 1997, Magnetic resonance in medicine.

[115]  J. Kucharczyk,et al.  Ischemic brain damage: reduction by sodium-calcium ion channel modulator RS-87476. , 1991, Radiology.

[116]  P. van Hecke,et al.  New Na(+)-H+ exchange inhibitor HOE 694 improves postischemic function and high-energy phosphate resynthesis and reduces Ca2+ overload in isolated perfused rabbit heart. , 1994, Circulation.

[117]  S. Williams In Vivo Proton Spectroscopy. Experimental Aspects and Potential , 1992 .

[118]  F. Hyder,et al.  Activation of single whisker barrel in rat brain localized by functional magnetic resonance imaging. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[119]  O. Jardetzky,et al.  1H NMR spectroscopy: an approach to evaluation of diseased skin in vivo. , 1989, The Journal of investigative dermatology.

[120]  B. Künnecke,et al.  Monoclonal antibody‐coated magnetite particles as contrast agents in magnetic resonance imaging of tumors , 1989, Magnetic resonance in medicine.

[121]  M D King,et al.  Identification of Collaterally Perfused Areas following Focal Cerebral Ischemia in the Rat by Comparison of Gradient Echo and Diffusion-Weighted MRI , 1995, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[122]  P. J. Hoopes,et al.  MRI contrast enhanced study of cartilage proteoglycan degradation in the rabbit knee , 1997, Magnetic resonance in medicine.

[123]  N. Szeverenyi,et al.  A quantitative one-dimensional magnetic resonance imaging technique in adjuvant arthritis: the assessment of disease progression and indomethacin efficacy. , 1995, The Journal of rheumatology.

[124]  M Ostergaard,et al.  Quantitative assessment of the synovial membrane in the rheumatoid wrist: an easily obtained MRI score reflects the synovial volume. , 1996, British journal of rheumatology.

[125]  M. Papisov,et al.  Macromolecular intravenous contrast agent for MR lymphography: characterization and efficacy studies. , 1996, Radiology.

[126]  R Weissleder,et al.  MR lymphography: study of a high-efficiency lymphotrophic agent. , 1994, Radiology.

[127]  M. Moskowitz,et al.  Neuronal nitric oxide synthase mutant mice show smaller infarcts and attenuated apparent diffusion coefficient changes in the peri‐infarct zone during focal cerebral ischemia , 1997, Magnetic resonance in medicine.

[128]  R. Semelka,et al.  MR imaging of the gastrointestinal tract. , 1995, Magnetic resonance imaging clinics of North America.

[129]  A. Koretsky,et al.  Phosphocreatine protects transgenic mouse liver expressing creatine kinase from hypoxia and ischemia. , 1993, The American journal of physiology.

[130]  Y. Shachar-Hill,et al.  Calcium measurements with a new high-affinity n.m.r. indicator in the isolated perfused heart. , 1993, The Biochemical journal.

[131]  M. Rudin,et al.  Reduction of neural damage in irreversible cerebral ischemia by calcium antagonists. , 1988, Neurochemical pathology.

[132]  W. V. van Gilst,et al.  The effects of short- and long-term treatment with an ACE-inhibitor in rats with myocardial infarction. , 1991, Basic research in cardiology.

[133]  C. Taylor,et al.  MRI detection of hyperoxia-induced lung edema in Zn-deficient rats. , 1990, Free radical biology & medicine.

[134]  K. Hossmann,et al.  Evolution of acute focal cerebral ischaemia in rats observed by localized 1H MRS, diffusion‐weighted MRI, and electrophysiological monitoring , 1995, NMR in biomedicine.

[135]  C. Hardy,et al.  Altered myocardial high-energy phosphate metabolites in patients with dilated cardiomyopathy. , 1991, American heart journal.

[136]  W. Bion,et al.  Learning from experience , 2007 .

[137]  H. B. Verheul,et al.  Changes in metabolites and tissue water status after focal ischemia in cat brain assessed with localized proton MR spectroscopy , 1994, Magnetic resonance in medicine.

[138]  D. Brooks Functional imaging techniques in the diagnosis of non-Alzheimer dementias. , 1996, Journal of neural transmission. Supplementum.

[139]  L. Martí-Bonmatí,et al.  Reduction of peristaltic artifacts on magnetic resonance imaging of the abdomen: a comparative evaluation of three drugs , 1996, Abdominal Imaging.

[140]  E. McVeigh,et al.  Noninvasive measurement of transmural gradients in myocardial strain with MR imaging. , 1991, Radiology.

[141]  Albert Macovski,et al.  MR Spectroscopic imaging of collagen: Tendons and knee menisci , 1995, Magnetic resonance in medicine.

[142]  E. Braunwald,et al.  Preservation of high-energy phosphates by verapamil in reperfused myocardium. , 1984, Circulation.

[143]  S. Caruthers,et al.  Relative quantification of pulmonary edema with noncontrast‐enhanced MRI , 1997, Journal of magnetic resonance imaging : JMRI.

[144]  F. Regan,et al.  MRI of bowel obstruction using the HASTE sequence. , 1996, Journal of computer assisted tomography.

[145]  O. Henriksen,et al.  Quantitative assessment of synovial inflammation by dynamic gadolinium-enhanced magnetic resonance imaging. A study of the effect of intra-articular methylprednisolone on the rate of early synovial enhancement. , 1996, British journal of rheumatology.

[146]  M. Rudin,et al.  Determination of creatine kinase kinetic parameters in rat brain by NMR magnetization transfer. Correlation with brain function. , 1993, The Journal of biological chemistry.

[147]  R. Turner,et al.  Functional mapping of the human visual cortex at 4 and 1.5 tesla using deoxygenation contrast EPI , 1993, Magnetic resonance in medicine.

[148]  M. Rudin,et al.  Decreased lumen size after balloon injury despite inhibition of neointimal thickening and antivasospastic treatment. , 1994, Cardiovascular research.

[149]  M. Rudin,et al.  Calcium Antagonists for Reduction of Brain Damage in Stroke , 1990, Journal of cardiovascular pharmacology.

[150]  J. Ulatowski,et al.  Rapid monitoring of changes in water diffusion coefficients during reversible ischemia in cat and rat brain , 1994, Magnetic resonance in medicine.

[151]  J. Waterton,et al.  High‐Resolution NMR imaging of an antigen‐induced arthritis in the Rabbit Knee , 1989, Magnetic resonance in medicine.

[152]  G K Radda,et al.  The use of NMR spectroscopy for the understanding of disease. , 1986, Science.

[153]  R. Shulman,et al.  Decreased muscle glucose transport/phosphorylation is an early defect in the pathogenesis of non-insulin-dependent diabetes mellitus. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[154]  Ravi S. Menon,et al.  Intrinsic signal changes accompanying sensory stimulation: functional brain mapping with magnetic resonance imaging. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[155]  D B Kopans,et al.  Benign and malignant breast lesions: differentiation with echo-planar MR imaging. , 1995, Radiology.

[156]  B. Rosen,et al.  Functional mapping of the human visual cortex by magnetic resonance imaging. , 1991, Science.

[157]  D. Tank,et al.  Brain magnetic resonance imaging with contrast dependent on blood oxygenation. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[158]  M. Fisher,et al.  Effect of basic fibroblast growth factor on experimental focal ischemia studied by diffusion-weighted and perfusion imaging. , 1996, Stroke.

[159]  A. Koretsky,et al.  Altering creatine kinase isoenzymes in transgenic mouse muscle by overexpression of the B subunit. , 1993, The American journal of physiology.

[160]  W. Aue,et al.  Phosphocreatine content and intracellular pH of calf muscle measured by phosphorus NMR spectroscopy in occlusive arterial disease of the legs , 1985, European journal of clinical investigation.

[161]  Charles R.scriver,et al.  The Metabolic basis of inherited disease , 1989 .

[162]  D Kunz,et al.  Use of frequency‐modulated radiofrequency pulses in MR imaging experiments , 1986, Magnetic resonance in medicine.

[163]  J R Griffiths,et al.  An Investigation of Tumor 1H Nuclear Magnetic Resonance Spectra by the Application of Chemometric Techniques , 1992, Magnetic resonance in medicine.

[164]  H. Degani,et al.  Tamoxifen enhances cell death in implanted MCF7 breast cancer by inhibiting endothelium growth. , 1994, Cancer research.

[165]  U. Keller,et al.  Early glycogenolysis and late glycogenesis in human liver after intravenous administration of galactose. , 1996, The American journal of physiology.

[166]  M. Rudin,et al.  Partial inhibition of the growth of transplanted dunning rat prostate tumors with the long-acting somatostatin analogue sandostatin (SMS 201-995). , 1988, Cancer research.

[167]  F. Ebner,et al.  Functional magnetic resonance imaging of human renal allografts during the post-transplant period: preliminary observations. , 1997, Magnetic resonance imaging.

[168]  M. Rudin,et al.  Calcium antagonists reduce the extent of infarction in rat middle cerebral artery occlusion model as determined by quantitative magnetic resonance imaging. , 1986, Stroke.

[169]  J. Koutcher,et al.  In vivo and ex vivo study of metabolic and cellular effects of 5-fluorouracil chemotherapy in a mouse mammary carcinoma. , 1997, Magnetic resonance imaging.

[170]  C. Sotak,et al.  Glycine site antagonist attenuates infarct size in experimental focal ischemia. Postmortem and diffusion mapping studies. , 1997, Stroke.

[171]  J. S. Cohen,et al.  NMR Studies of Metabolism of Cells and Perfused Organs , 1992 .

[172]  J. Seelig,et al.  Analysis of glycogen storage disease by in vivo 13C NMR comparison of normal volunteers with a patient , 1990, Magnetic resonance in medicine.

[173]  R. Ehman,et al.  Acute myocardial ischemia: magnetic resonance contrast enhancement with gadolinium-DTPA. , 1984, Radiology.

[174]  B. Dardzinski,et al.  MRI diffusion mapping of reversible and irreversible ischemic injury in focal brain ischemia , 1994, Neurology.

[175]  H. Degani,et al.  Angiogenic response of MCF7 human breast cancer to hormonal treatment: Assessment by dynamic GdDTPA‐enhanced MRI at high spatial resolution , 1996, Journal of magnetic resonance imaging : JMRI.

[176]  M Chopp,et al.  IN VIVO 31P NMR STUDY OF COMBINED HYPERTHERMIA and PHOTODYNAMIC THERAPIES OF MAMMARY CARCINOMA IN THE MOUSE , 1991, Photochemistry and photobiology.

[177]  J C Lindon,et al.  Pattern recognition classification of the site of nephrotoxicity based on metabolic data derived from proton nuclear magnetic resonance spectra of urine. , 1994, Molecular pharmacology.

[178]  D. Burstein,et al.  Determination of fixed charge density in cartilage using nuclear magnetic resonance , 1992, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[179]  G. Cameron,et al.  Human in vivo phosphorus 31 magnetic resonance spectroscopy of psoriasis. A noninvasive tool to monitor response to treatment and to study pathophysiology of the disease. , 1994, Journal of the American Academy of Dermatology.

[180]  H. Fujiki,et al.  Effects of OPC-18790, a new positive inotropic agent, on energetics in the ischaemic canine heart: a 31P-MRS study. , 1995, Cardiovascular research.

[181]  M. Rudin,et al.  Dihydropyridine calcium antagonists reduce the consumption of high-energy phosphates in the rat brain. A study using combined 31P/1H magnetic resonance spectroscopy and 31P saturation transfer. , 1989, The Journal of pharmacology and experimental therapeutics.

[182]  M. Raschack,et al.  Oedema reduction by levemopamil in focal cerebral ischaemia of spontaneously hypertensive rats studied by magnetic resonance imaging. , 1994, European journal of pharmacology.

[183]  D. Wilson,et al.  Magnetic Resonance Imaging and Morphometric Quantitation of Cartilage Histology after Chronic Infusion of Interleukin 1 in Rabbit Knees , 1993, Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine.

[184]  H K Genant,et al.  MR imaging of the arthritic knee: improved discrimination of cartilage, synovium, and effusion with pulsed saturation transfer and fat-suppressed T1-weighted sequences. , 1994, Radiology.

[185]  J. Kucharczyk,et al.  NG-nitro-L-arginine delays the development of brain injury during focal ischemia in rats. , 1995, Stroke.

[186]  J A Frank,et al.  Functional MR of the kidney , 1991, Magnetic resonance in medicine.

[187]  O. Ernst,et al.  Oral administration of a low‐cost negative contrast agent: A three‐year experience in routine practice , 1997, Journal of magnetic resonance imaging : JMRI.

[188]  R. Walsworth,et al.  Temporal dynamics of hyperpolarized 129Xe resonances in living rats. , 1996, Journal of magnetic resonance. Series B.

[189]  R. Weissleder,et al.  MR Lymphography with a Lymphotropic T1‐Type MR Contrast Agent: Gd‐DTPA‐PGM , 1995, Magnetic resonance in medicine.

[190]  H. Linardou,et al.  Review: advances in monoclonal antibody tumour targeting. , 1993, Journal of drug targeting.

[191]  M. Rudin,et al.  The role of magnetic resonance imaging and spectroscopy in transplantation: from animal models to man , 2000, NMR in biomedicine.

[192]  K Ugurbil,et al.  Functional and bioenergetic consequences of postinfarction left ventricular remodeling in a new porcine model. MRI and 31 P-MRS study. , 1996, Circulation.

[193]  J. Franconi,et al.  First‐pass evaluation of renal perfusion with turboflash MR imaging and superparamagnetic iron oxide particles , 1993, Journal of magnetic resonance imaging : JMRI.

[194]  R. Kauppinen,et al.  Transgenic rats as models for studying the role of ornithine decarboxylase expression in permanent middle cerebral artery occlusion. , 1997, Stroke.

[195]  D. Graham,et al.  Focal Cerebral Ischaemia in the Rat: 1. Description of Technique and Early Neuropathological Consequences following Middle Cerebral Artery Occlusion , 1981, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[196]  N. Beckmann Carbon-13 NMR spectroscopy of biological systems , 1995 .

[197]  O Jolivet,et al.  In vivo hydration profile in skin layers by high-resolution magnetic resonance imaging. , 1994, Skin pharmacology : the official journal of the Skin Pharmacology Society.

[198]  U. Keller,et al.  Noninvaive observation of hepatic glycogen formation in man by13C MRS after Orl and intravenous glucose administration , 1993, Magnetic resonance in medicine.

[199]  W. Gefter,et al.  Magnetic resonance imaging in the evaluation of lung cancer. , 1990, Seminars in roentgenology.

[200]  J. Kucharczyk,et al.  Hyperglycemia augments ischemic brain injury: in vivo MR imaging/spectroscopic study with nicardipine in cats with occluded middle cerebral arteries. , 1991, AJNR. American journal of neuroradiology.

[201]  A. Koretsky,et al.  NMR detection of creatine kinase expressed in liver of transgenic mice: determination of free ADP levels. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[202]  P. Bottomley,et al.  Assessment of pharmacological treatment of myocardial infarction by phosphorus-31 NMR with surface coils. , 1981, Science.

[203]  G M Hutchins,et al.  Relation of regional cross-fiber shortening to wall thickening in the intact heart. Three-dimensional strain analysis by NMR tagging. , 1994, Circulation.

[204]  K Scheffler,et al.  Aluminum‐27 nuclear magnetic resonance spectroscopy and imaging of the human gastric lumen , 1996, Magnetic resonance in medicine.

[205]  R. Damadian Tumor Detection by Nuclear Magnetic Resonance , 1971, Science.

[206]  S. Neubauer,et al.  Contributions of 31P-magnetic resonance spectroscopy to the understanding of dilated heart muscle disease. , 1995, European heart journal.

[207]  J. Koutcher,et al.  In vivo and in vitro studies of cyclophosphamide chemotherapy in a mouse mammary carcinoma by 31P NMR spectroscopy , 1995, NMR in biomedicine.

[208]  C. Koboldt,et al.  Novel terphenyls as selective cyclooxygenase-2 inhibitors and orally active anti-inflammatory agents. , 1996, Journal of medicinal chemistry.

[209]  C. Standertskjöld-Nordenstam,et al.  Dynamic fast-gradient echo MR imaging of pancreatic tumours. , 1997, European journal of radiology.

[210]  D. Burstein,et al.  Magnetization transfer in cartilage and its constituent macromolecules , 1995, Magnetic resonance in medicine.

[211]  T. Hougen,et al.  Insulin effects on monovalent cation transport and Na-K-ATPase activity. , 1978, The American journal of physiology.

[212]  J. Mandeville,et al.  Neuroprotection with NBQX in rat focal cerebral ischemia. Effects on ADC probability distribution functions and diffusion-perfusion relationships. , 1997, Stroke.

[213]  L. Pitts,et al.  Magnetic resonance imaging in the evaluation of nimodipine-treated acute experimental focal cerebral ischemia. , 1986, Acta radiologica. Supplementum.

[214]  In vivo animal tests of an artifact-free contrast agent for gastrointestinal MRI. , 1997, Magnetic resonance imaging.

[215]  S. Ogawa Brain magnetic resonance imaging with contrast-dependent oxygenation , 1990 .

[216]  B. Rosen,et al.  A functional MRI study of subjects recovered from hemiparetic stroke. , 1997, Stroke.

[217]  J. Balligand,et al.  Nitric oxide inhibits creatine kinase and regulates rat heart contractile reserve. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[218]  H. Degani,et al.  Dynamic contrast-enhanced magnetic resonance imaging reveals stress-induced angiogenesis in MCF7 human breast tumors. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[219]  D C Noll,et al.  MR imaging of lung parenchyma: a solution to susceptibility. , 1992, Radiology.

[220]  S. Neubauer,et al.  Verapamil attenuates ATP depletion during hypoxia: 31P NMR studies of the isolated rat heart. , 1989, Journal of molecular and cellular cardiology.

[221]  M. Laser,et al.  Impairment of energy metabolism in intact residual myocardium of rat hearts with chronic myocardial infarction. , 1995, The Journal of clinical investigation.

[222]  J. Kucharczyk,et al.  MR evaluation of calcium entry blockers with putative cerebroprotective effects in acute cerebral ischaemia. , 1990, Acta neurochirurgica. Supplementum.

[223]  Scott E. Fraser,et al.  A SMART MAGNETIC RESONANCE IMAGING AGENT THAT REPORTS ON SPECIFIC ENZYMATIC ACTIVITY , 1997 .

[224]  M W Weiner,et al.  Correlation of early reduction in the apparent diffusion coefficient of water with blood flow reduction during middle cerebral artery occlusion in rats , 1995, Magnetic resonance in medicine.

[225]  R. Wolf Synthesis, transfer, and phosphorylation of phosphoinositides in cardiac membranes. , 1990, The American journal of physiology.

[226]  D. L. Johnston,et al.  Reduced substrate oxidation in postischemic myocardium: 13C and 31P NMR analyses. , 1990, The American journal of physiology.

[227]  A. Howseman,et al.  Localized proton NMR observation of [3‐13C] lactate in stroke after [1‐13C] glucose infusion , 1991, Magnetic resonance in medicine.

[228]  R. Weissleder,et al.  MION-ASF: biokinetics of an MR receptor agent. , 1993, Magnetic resonance imaging.

[229]  Alan C. Evans,et al.  The Role of MRI in clinical trials of multiple sclerosis: Comparison of image processing techniques , 1997, Annals of neurology.

[230]  P. Ros,et al.  Superparamagnetic iron oxide (SPIO) as an oral contrast agent in gastrointestinal (GI) magnetic resonance imaging (MRI): comparison with state-of-the-art computed tomography (CT). , 1996, Magnetic Resonance Imaging.

[231]  O. Haraldseth,et al.  Perfusion and diffusion-weighted MR imaging for in vivo evaluation of treatment with U74389G in a rat stroke model. , 1995, Stroke.

[232]  C. Kramer,et al.  Remote noninfarcted region dysfunction soon after first anterior myocardial infarction. A magnetic resonance tagging study. , 1996, Circulation.

[233]  R Pórszász,et al.  Signal changes in the spinal cord of the rat after injection of formalin into the hindpaw: characterization using functional magnetic resonance imaging. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[234]  G. Glazer Radiologic staging of lung cancer using CT and MRI. , 1989, Chest.

[235]  P. Chou,et al.  MR of leptomeningeal melanosis in children. , 1995, European journal of radiology.

[236]  J. Kucharczyk,et al.  Evaluation of recombinant human basic fibroblast growth factor (rhbFGF) as a cerebroprotective agent using high speed MR imaging , 1995, Brain Research.

[237]  I. Francis,et al.  MR imaging of the gastrointestinal tract with i.v., gadolinium and diluted barium oral contrast media compared with unenhanced MR imaging and CT. , 1997, AJR. American journal of roentgenology.

[238]  D. Leibfritz,et al.  Cardioprotective efficiency of dihydrolipoic acid in working rat hearts during hypoxia and reoxygenation. 31P nuclear magnetic resonance investigations. , 1993, Arzneimittel-Forschung.

[239]  Krestin Gp,et al.  Magnetic resonance imaging of the kidneys: current status. , 1994 .

[240]  Michael Chopp,et al.  The temporal evolution of MRI tissue signatures after transient middle cerebral artery occlusion in rat , 1997, Journal of the Neurological Sciences.

[241]  R. Weissleder,et al.  Asialoglycoprotein receptor function in benign liver disease: evaluation with MR imaging. , 1991, Radiology.

[242]  D. Šuput,et al.  Water proton NMR relaxation mechanisms in lung tissue , 1988, Magnetic resonance in medicine.

[243]  J W Belliveau,et al.  Functional mapping of activated human primary cortex with a clinical MR imaging system. , 1993, Radiology.

[244]  M. Rudin,et al.  Effects of calcium antagonists on high‐energy phosphates in ischemic rat brain measured by 31P NMR spectroscopy , 1987, Magnetic resonance in medicine.

[245]  L. Schad,et al.  Sensorimotor Cortex and Supplementary Motor Area Changes in Schizophrenia , 1995, British Journal of Psychiatry.

[246]  M. Rudin,et al.  Magnetic resonance imaging for the evaluation of rejection of a kindney allograft in the rat , 1996, Transplant international : official journal of the European Society for Organ Transplantation.

[247]  C. Higgins,et al.  Detection and characterization of acute myocardial infarction in man with use of gated magnetic resonance. , 1985, Circulation.

[248]  P. Lauterbur,et al.  Ferromagnetic particles as contrast agents for magnetic resonance imaging of liver and spleen , 1986, Magnetic resonance in medicine.

[249]  P Boesiger,et al.  True myocardial motion tracking , 1994, Magnetic resonance in medicine.

[250]  W J Rogers,et al.  Rotational deformation of the canine left ventricle measured by magnetic resonance tagging: effects of catecholamines, ischaemia, and pacing. , 1994, Cardiovascular research.

[251]  J. Trevithick,et al.  Topical tocopherol acetate reduces post-UVB, sunburn-associated erythema, edema, and skin sensitivity in hairless mice. , 1992, Archives of biochemistry and biophysics.

[252]  Pradeep Rajagopalan,et al.  Nuclear magnetic resonance spectroscopy: A review of neuropsychiatric applications , 1995, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[253]  M. Rudin,et al.  Strain-dependent drug effects in rat middle cerebral artery occlusion model of stroke. , 1995, The Journal of pharmacology and experimental therapeutics.

[254]  S. Sarkar,et al.  Disease-modifying activity of SK&F 106615 in rat adjuvant-induced arthritis. Multiparameter analysis of disease magnetic resonance imaging and bone mineral density measurements. , 1996, Arthritis and rheumatism.

[255]  Á. Tósaki,et al.  Adenosine triphosphate-sensitive potassium channel blocking agent ameliorates, but the opening agent aggravates, ischemia/reperfusion-induced injury. Heart function studies in nonfibrillating isolated hearts. , 1994, Journal of the American College of Cardiology.

[256]  T. Carpenter,et al.  High-resolution magnetic resonance imaging of arthritic pathology in the rat knee , 1994, Skeletal Radiology.

[257]  H. B. Verheul,et al.  Comparison of diffusion‐weighted MRI with changes in cell volume in a rat model of brain injury , 1994, NMR in biomedicine.

[258]  G. Shulman,et al.  Glucose metabolism distal to a critical coronary stenosis in a canine model of low-flow myocardial ischemia. , 1996, The Journal of clinical investigation.

[259]  G. Bydder,et al.  NMR imaging of the brain using spin-echo sequences. , 1982, Clinical Radiology.

[260]  M. Rudin,et al.  Pharmacological inhibition of restenosis: learning from experience. , 1995, Trends in pharmacological sciences.

[261]  A. Benabid,et al.  Two‐dimensional 1H spectroscopic imaging for evaluating the local metabolic response to focal ischemia in the conscious rat , 1992, NMR in biomedicine.

[262]  M. Yuen,et al.  Herpes simplex virus type 2 infection in a 5‐year‐old boy presenting with recurrent chest wall vesicles and a possible history of herpes encephalitis , 1997, The British journal of dermatology.

[263]  J Seega,et al.  Diffusion- and T2-weighted imaging: evaluation of oedema reduction in focal cerebral ischaemia by the calcium and serotonin antagonist levemopamil. , 1993, Magnetic resonance imaging.

[264]  R G Shulman,et al.  Quantitation of hepatic glycogenolysis and gluconeogenesis in fasting humans with 13C NMR. , 1991, Science.

[265]  Markus Rudin,et al.  Magnetic resonance angiography of the rat cerebrovascular system without the use of contrast agents , 1999, NMR in biomedicine.

[266]  G. Fagg,et al.  Differing effects of α-difluoromethylornithine and CGP 40116 on polyamine levels and infarct volume in a rat model of focal cerebral ischaemia , 1992, Neuroscience Letters.

[267]  M Thelen,et al.  Imaging of the lungs using 3he MRI: Preliminary clinical experience in 18 patients with and without lung disease , 1997, Journal of magnetic resonance imaging : JMRI.

[268]  I. Gribbestad,et al.  In vivo tissue pharmacokinetics by fluorine magnetic resonance spectroscopy: A study of liver and muscle disposition of fleroxacin in humans , 1990, Clinical pharmacology and therapeutics.

[269]  T. Foster,et al.  Effectiveness of delta-aminolevulinic acid-induced protoporphyrin as a photosensitizer for photodynamic therapy in vivo. , 1995, Cancer research.

[270]  R. Nagel,et al.  High expression of human beta S- and alpha-globins in transgenic mice: erythrocyte abnormalities, organ damage, and the effect of hypoxia. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[271]  A. Heerschap,et al.  Effect of modulators on 5-fluorouracil metabolite patterns in murine colon carcinoma determined by in vitro 19F nuclear magnetic resonance spectroscopy. , 1994, Cancer research.

[272]  R. Coombes,et al.  31P-nuclear magnetic resonance spectroscopy studies of the response of rat mammary tumors to endocrine therapy. , 1988, Cancer research.

[273]  CGP 53153: a new potent inhibitor of 5α-reductase , 1996, The Journal of Steroid Biochemistry and Molecular Biology.

[274]  R. Shulman,et al.  Nuclear Magnetic Resonance Studies of Muscle and Applications to Exercise and Diabetes , 1996, Diabetes.

[275]  T. A. Carpenter,et al.  A magnetic resonance imaging study of joint degeneration in the guinea pig knee. , 1993, Agents and actions. Supplements.

[276]  D M Shames,et al.  Mammary carcinoma model: correlation of macromolecular contrast-enhanced MR imaging characterizations of tumor microvasculature and histologic capillary density. , 1996, Radiology.

[277]  H. Zerwes,et al.  Time Course of Spirapril‐Induced Structural and Functional Changes After Myocardial Infarction in Rats Followed with Magnetic Resonance Imaging , 1993, Journal of cardiovascular pharmacology.

[278]  R Weissleder,et al.  Targeted contrast agents in MR imaging. , 1996, Magnetic resonance imaging clinics of North America.

[279]  P R Allegrini,et al.  Application of magnetic resonance imaging to the measurement of neurodegeneration in rat brain: MRI data correlate strongly with histology and enzymatic analysis. , 1992, Magnetic resonance imaging.

[280]  L W Hedlund,et al.  In vivo He-3 MR images of guinea pig lungs. , 1996, Radiology.

[281]  B. Rosen,et al.  Pitfalls in MR measurement of tissue blood flow with intravascular tracers: Which mean transit time? , 1993, Magnetic resonance in medicine.

[282]  B. Furr,et al.  The development of Casodex (bicalutamide): preclinical studies. , 1996, European urology.

[283]  M. Rudin,et al.  Analysis of tracer transit in rat brain after carotid artery and femoral vein administrations using linear system theory. , 1997, Magnetic resonance imaging.

[284]  E. McVeigh,et al.  Myocardial tagging in polar coordinates with use of striped tags. , 1990, Radiology.

[285]  G. Fagg,et al.  Characterization of the Cerebroprotective Efficacy of the Competitive NMDA Receptor Antagonist CGP40116 in a Rat Model of Focal Cerebral Ischemia: An in vivo Magnetic Resonance Imaging Study , 1993, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[286]  J. Evelhoch,et al.  Response-specific adriamycin sensitivity markers provided by in vivo 31P nuclear magnetic resonance spectroscopy in murine mammary adenocarcinomas. , 1987, Cancer research.

[287]  Target‐specific superparamagnetic MR contrast agents , 1991, Magnetic resonance in medicine.

[288]  Y. Fujise,et al.  Creatine kinase kinetics in diabetic cardiomyopathy. , 1995, The American journal of physiology.

[289]  K. Gersonde,et al.  MR microimaging of articular cartilage and contrast enhancement by manganese ions , 1992, Magnetic resonance in medicine.

[290]  R Felix,et al.  Role of High-Resolution Magnetic Resonance Imaging for Differentiating Melanin-Containing Skin Tumors , 1995, Investigative radiology.

[291]  L. Nilsson Liver glycogen content in man in the postabsorptive state. , 1973, Scandinavian journal of clinical and laboratory investigation.

[292]  B. Drayer,et al.  Chronic adult cerebral infarction studied by phosphorus NMR spectroscopy. , 1986, Radiology.

[293]  Arend Heerschap,et al.  Skeletal muscles of mice deficient in muscle creatine kinase lack burst activity , 1993, Cell.

[294]  P F Renshaw,et al.  Ferromagnetic contrast agents: A new approach , 1986, Magnetic resonance in medicine.

[295]  R. Weissleder,et al.  Pancreatic receptors: initial feasibility studies with a targeted contrast agent for MR imaging. , 1994, Radiology.

[296]  T J Brady,et al.  True three-dimensional nuclear magnetic resonance neuro-imaging in ischemic stroke: correlation of NMR, X-ray CT and pathology. , 1983, Stroke.

[297]  Robert R. Edelman,et al.  Noninvasive assessment of regional ventilation in the human lung using oxygen–enhanced magnetic resonance imaging , 1996, Nature Medicine.

[298]  M. Mintun,et al.  Nonoxidative glucose consumption during focal physiologic neural activity. , 1988, Science.

[299]  Ravi S. Menon,et al.  Functional imaging of human motor cortex at high magnetic field. , 1993, Journal of neurophysiology.

[300]  J R Griffiths,et al.  Pattern recognition of 31P magnetic resonance spectroscopy tumour spectra obtained in vivo , 1993, NMR in biomedicine.

[301]  M. Rudin,et al.  Cerebrovascular, biochemical, and cytoprotective effects of isradipine in laboratory animals. , 1989, The American journal of medicine.

[302]  A. Sherry,et al.  Analysis of tricarboxylic acid cycle of the heart using 13C isotope isomers. , 1990, The American journal of physiology.

[303]  G K Radda,et al.  Examination of a case of suspected McArdle's syndrome by 31P nuclear magnetic resonance. , 1981, The New England journal of medicine.

[304]  O Jolivet,et al.  In vivo proton relaxation times analysis of the skin layers by magnetic resonance imaging. , 1991, The Journal of investigative dermatology.

[305]  J R MacFall,et al.  MR microscopy of the rat lung using projection reconstruction , 1993, Magnetic resonance in medicine.

[306]  T. Vogl,et al.  Failure of gadopentetate dimeglumine-enhanced, high-resolution magnetic resonance imaging to differentiate among melanin-containing skin tumors. , 1996, Academic radiology.

[307]  G Liu,et al.  Functional brain MR imaging based on bolus tracking with a fast T2*-sensitized gradient-echo method. , 1994, Magnetic resonance imaging.

[308]  P. Mansfield Multi-planar image formation using NMR spin echoes , 1977 .

[309]  M. Moseley,et al.  Time-course and treatment response with SNX-111, an N-type calcium channel blocker, in a rodent model of focal cerebral ischemia using diffusion-weighted MRI , 1996, Brain Research.

[310]  H Azhari,et al.  A noninvasive comparative study of myocardial strains in ischemic canine hearts using tagged MRI in 3-D. , 1995, The American journal of physiology.

[311]  O Jolivet,et al.  Characterization of the skin in vivo by high resolution magnetic resonance imaging: water behavior and age-related effects. , 1993, The Journal of investigative dermatology.

[312]  Noninvasive determination of regional cerebral blood flow in rats using dynamic imaging with Gd(DTPA) , 1991, Magnetic resonance in medicine.

[313]  A. Koretsky,et al.  Contractile and metabolic effects of increased creatine kinase activity in mouse skeletal muscle. , 1996, The American journal of physiology.

[314]  J Listerud,et al.  Multi‐Slice, Breathhold Imaging of the Lung with Submillisecond Echo Times , 1995, Magnetic resonance in medicine.

[315]  R. Wilson,et al.  Myocardial perfusion reserve: assessment with multisection, quantitative, first-pass MR imaging. , 1997, Radiology.

[316]  T. Ng,et al.  Application ofin vivo NMR spectroscopy to cancer , 1984, Magnetic resonance in medicine.

[317]  P. Boesiger,et al.  Measurement of proximal and distal gastric motility with magnetic resonance imaging. , 1996, The American journal of physiology.

[318]  T J Brady,et al.  Magnetically labeled secretin retains receptor affinity to pancreas acinar cells. , 1996, Bioconjugate chemistry.

[319]  W S Hinshaw,et al.  Cranial anatomy and detection of ischemic stroke in the cat by nuclear magnetic resonance imaging. , 1982, Radiology.

[320]  P. Bottomley,et al.  Cerebral energy metabolism in rats studied by phosphorus nuclear magnetic resonance using surface coils. , 1982, Magnetic resonance imaging.

[321]  J. Douillard,et al.  Selective modification of NMR relaxation time in human colorectal carcinoma by using gadolinium-diethylenetriaminepentaacetic acid conjugated with monoclonal antibody 19-9. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[322]  A. Kang,et al.  Autoimmunity to type II collagen an experimental model of arthritis , 1977, The Journal of experimental medicine.

[323]  R. Paola,et al.  Correlation Between Contrast Enhancement in Dynamic Magnetic Resonance Imaging of the Breast and Tumor Angiogenesis , 1994, Investigative radiology.

[324]  M Hoehn-Berlage,et al.  Variation of functional MRI signal in response to frequency of somatosensory stimulation in α‐chloralose anesthetized rats , 1996, Magnetic resonance in medicine.

[325]  Joseph P. Broderick,et al.  Tissue plasminogen activator for acute ischemic stroke. The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. , 1995 .

[326]  J Hennig,et al.  The importance of the voxel size in clinical 1H spectroscopy of the human brain , 1989, NMR in biomedicine.

[327]  M. Osteaux,et al.  Inhibitory effect of somatostatin analogue RC-160 on the growth of hepatic metastases of colon cancer in rats: a study with magnetic resonance imaging. , 1992, Cancer research.

[328]  M. Rudin,et al.  Quantitative magnetic resonance imaging of estradiol‐induced pituitary hyperplasia in rats , 1988, Magnetic resonance in medicine.

[329]  E. Zerhouni,et al.  Human heart: tagging with MR imaging--a method for noninvasive assessment of myocardial motion. , 1988, Radiology.

[330]  L D Hall,et al.  Cardiac tagging in the rat using a DANTE sequence , 1991, Magnetic resonance in medicine.

[331]  C Lemaire,et al.  Osteoarthritis in rhesus macaque knee joint: quantitative magnetic resonance imaging tissue characterization of articular cartilage. , 1995, The Journal of rheumatology.

[332]  W. Happer,et al.  Biological magnetic resonance imaging using laser-polarized 129Xe , 1994, Nature.

[333]  M. Raichle,et al.  Focal physiological uncoupling of cerebral blood flow and oxidative metabolism during somatosensory stimulation in human subjects. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[334]  H F Li,et al.  In vivo MR imaging and spectroscopy using hyperpolarized 129Xe , 1996, Magnetic resonance in medicine.

[335]  K. Petersen,et al.  Impaired net hepatic glycogen synthesis in insulin-dependent diabetic subjects during mixed meal ingestion. A 13C nuclear magnetic resonance spectroscopy study. , 1995, The Journal of clinical investigation.

[336]  H. B. Verheul,et al.  Temporal evolution of NMDA-induced excitoxicity in the neonatal rat brain measured with 1H nuclear magnetic resonance imaging , 1993, Brain Research.

[337]  G. Jackson,et al.  New Techniques in Magnetic Resonance and Epilepsy , 1994, Epilepsia.