MR Imaging Biomarkers in Oncology Clinical Trials.

The authors discuss eight areas of quantitative MR imaging that are currently used (RECIST, DCE-MR imaging, DSC-MR imaging, diffusion MR imaging) in clinical trials or emerging (CEST, elastography, hyperpolarized MR imaging, multiparameter MR imaging) as promising techniques in diagnosing cancer and assessing or predicting response of cancer to therapy. Illustrative applications of the techniques in the clinical setting are summarized before describing the current limitations of the methods.

[1]  Jan Wolber,et al.  Detecting tumor response to treatment using hyperpolarized 13C magnetic resonance imaging and spectroscopy , 2007, Nature Medicine.

[2]  Modeling the Effect of Intra-Voxel Diffusion of Contrast Agent on the Quantitative Analysis of Dynamic Contrast Enhanced Magnetic Resonance Imaging , 2014, PloS one.

[3]  A. Padhani,et al.  Reproducibility of dynamic contrast‐enhanced MRI in human muscle and tumours: comparison of quantitative and semi‐quantitative analysis , 2002, NMR in biomedicine.

[4]  V. Vilgrain,et al.  MR elastography of liver tumours: value of viscoelastic properties for tumour characterisation , 2012, European Radiology.

[5]  Thomas E Yankeelov,et al.  Dynamic Contrast Enhanced Magnetic Resonance Imaging in Oncology: Theory, Data Acquisition, Analysis, and Examples. , 2007, Current medical imaging reviews.

[6]  F. De Keyzer,et al.  Chemoembolization for hepatocellular carcinoma: 1-month response determined with apparent diffusion coefficient is an independent predictor of outcome. , 2014, Radiology.

[7]  A. K. Poyraz,et al.  Diffusion‐weighted MRI of fatty liver , 2012, Journal of magnetic resonance imaging : JMRI.

[8]  Geert Molenberghs,et al.  Relation between tumour response to first-line chemotherapy and survival in advanced colorectal cancer: a meta-analysis , 2000, The Lancet.

[9]  Steinar Lundgren,et al.  Predicting survival and early clinical response to primary chemotherapy for patients with locally advanced breast cancer using DCE‐MRI , 2009, Journal of magnetic resonance imaging : JMRI.

[10]  Pernille R. Jensen,et al.  Magnetic resonance imaging of pH in vivo using hyperpolarized 13C-labelled bicarbonate , 2008, Nature.

[11]  Hiroto Hatabu,et al.  Hyperpolarized (129)Xe MRI: a viable functional lung imaging modality? , 2007, European journal of radiology.

[12]  M. Knopp,et al.  Estimating kinetic parameters from dynamic contrast‐enhanced t1‐weighted MRI of a diffusable tracer: Standardized quantities and symbols , 1999, Journal of magnetic resonance imaging : JMRI.

[13]  Matthew J. Paszek,et al.  The Tension Mounts: Mechanics Meets Morphogenesis and Malignancy , 2004, Journal of Mammary Gland Biology and Neoplasia.

[14]  K. D. Atkinson,et al.  Reversible Interactions with para-Hydrogen Enhance NMR Sensitivity by Polarization Transfer , 2009, Science.

[15]  J Jack Lee,et al.  Change in tumor size by RECIST correlates linearly with overall survival in phase I oncology studies. , 2012, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[16]  John P. Mugler,et al.  Hyperpolarized 129Xe MRI of the human lung , 2013, Journal of magnetic resonance imaging : JMRI.

[17]  M. Gilbert,et al.  Diffusion MRI quality control and functional diffusion map results in ACRIN 6677/RTOG 0625: A multicenter, randomized, phase II trial of bevacizumab and chemotherapy in recurrent glioblastoma , 2015, International journal of oncology.

[18]  Gregory Karczmar,et al.  Dynamic contrast-enhanced magnetic resonance imaging pharmacodynamic biomarker study of sorafenib in metastatic renal carcinoma. , 2008, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[19]  C. James,et al.  Detection of early response to temozolomide treatment in brain tumors using hyperpolarized 13C MR metabolic imaging , 2011, Journal of magnetic resonance imaging : JMRI.

[20]  Jinyuan Zhou,et al.  MR imaging of high-grade brain tumors using endogenous protein and peptide-based contrast , 2010, NeuroImage.

[21]  A P Pathak,et al.  Utility of simultaneously acquired gradient‐echo and spin‐echo cerebral blood volume and morphology maps in brain tumor patients , 2000, Magnetic resonance in medicine.

[22]  N. deSouza,et al.  Diffusion-weighted magnetic resonance imaging and its application to cancer , 2006, Cancer imaging : the official publication of the International Cancer Imaging Society.

[23]  Thomas E Yankeelov,et al.  Assessing the reproducibility of dynamic contrast enhanced magnetic resonance imaging in a murine model of breast cancer , 2013, Magnetic resonance in medicine.

[24]  Jung Hee Shin,et al.  Role of diffusion-weighted imaging as an adjunct to contrast-enhanced breast MRI in evaluating residual breast cancer following neoadjuvant chemotherapy. , 2014, European journal of radiology.

[25]  Richard L Ehman,et al.  MR elastography derived shear stiffness—a new imaging biomarker for the assessment of early tumor response to chemotherapy , 2014, Magnetic resonance in medicine.

[26]  P. Choyke,et al.  Prostate cancer: value of multiparametric MR imaging at 3 T for detection--histopathologic correlation. , 2010, Radiology.

[27]  Mithat Gönen,et al.  Quantitative imaging biomarkers: A review of statistical methods for technical performance assessment , 2015, Statistical methods in medical research.

[28]  R. T. Branca,et al.  Detection of brown adipose tissue and thermogenic activity in mice by hyperpolarized xenon MRI , 2014, Proceedings of the National Academy of Sciences.

[29]  Baris Turkbey,et al.  Multiparametric 3T prostate magnetic resonance imaging to detect cancer: histopathological correlation using prostatectomy specimens processed in customized magnetic resonance imaging based molds. , 2011, The Journal of urology.

[30]  D. Sullivan,et al.  A collaborative enterprise for multi-stakeholder participation in the advancement of quantitative imaging. , 2011, Radiology.

[31]  Jinyuan Zhou,et al.  Optimization of the irradiation power in chemical exchange dependent saturation transfer experiments. , 2005, Journal of magnetic resonance.

[32]  Ralph Sinkus,et al.  Diagnostic value of MR elastography in addition to contrast-enhanced MR imaging of the breast—initial clinical results , 2010, European Radiology.

[33]  Corinne Balleyguier,et al.  Evaluation of Breast Lesions Using Sonographic Elasticity Imaging , 2012, Journal of ultrasound in medicine : official journal of the American Institute of Ultrasound in Medicine.

[34]  Thomas E. Yankeelov,et al.  Practical Dynamic Contrast Enhanced MRI in Small Animal Models of Cancer: Data Acquisition, Data Analysis, and Interpretation , 2012, Pharmaceutics.

[35]  Thomas E Yankeelov,et al.  Multiparametric Magnetic Resonance Imaging for Predicting Pathological Response After the First Cycle of Neoadjuvant Chemotherapy in Breast Cancer , 2015, Investigative radiology.

[36]  Thomas E Yankeelov,et al.  Clinically Relevant Modeling of Tumor Growth and Treatment Response , 2013, Science Translational Medicine.

[37]  Donald E Ingber,et al.  Cell tension, matrix mechanics, and cancer development. , 2005, Cancer cell.

[38]  Thomas E Yankeelov,et al.  Integration of quantitative DCE-MRI and ADC mapping to monitor treatment response in human breast cancer: initial results. , 2007, Magnetic resonance imaging.

[39]  R S Balaban,et al.  Determination of pH using water protons and chemical exchange dependent saturation transfer (CEST) , 2000, Magnetic resonance in medicine.

[40]  A Gregory Sorensen,et al.  Relaxation‐compensated fast multislice amide proton transfer (APT) imaging of acute ischemic stroke , 2008, Magnetic resonance in medicine.

[41]  R M Weisskoff,et al.  Relative cerebral blood volume maps corrected for contrast agent extravasation significantly correlate with glioma tumor grade, whereas uncorrected maps do not. , 2006, AJNR. American journal of neuroradiology.

[42]  Triantafyllos Stylianopoulos,et al.  The role of mechanical forces in tumor growth and therapy. , 2014, Annual review of biomedical engineering.

[43]  B. D. Ward,et al.  Characterization of a first-pass gradient-echo spin-echo method to predict brain tumor grade and angiogenesis. , 2004, AJNR. American journal of neuroradiology.

[44]  P. Grenier,et al.  MR imaging of intravoxel incoherent motions: application to diffusion and perfusion in neurologic disorders. , 1986, Radiology.

[45]  Nola M. Hylton,et al.  Diffusion-weighted MRI: influence of intravoxel fat signal and breast density on breast tumor conspicuity and apparent diffusion coefficient measurements. , 2011, Magnetic resonance imaging.

[46]  M Paesmans,et al.  Response to chemotherapy has predictive value for further survival of patients with advanced non-small cell lung cancer: 10 years experience of the European Lung Cancer Working Party. , 1997, European journal of cancer.

[47]  C. Kuhl,et al.  Dynamic breast MR imaging: are signal intensity time course data useful for differential diagnosis of enhancing lesions? , 1999, Radiology.

[48]  R. Balaban,et al.  Magnetization transfer contrast (MTC) and tissue water proton relaxation in vivo , 1989, Magnetic resonance in medicine.

[49]  John Kurhanewicz,et al.  Analysis of cancer metabolism by imaging hyperpolarized nuclei: prospects for translation to clinical research. , 2011, Neoplasia.

[50]  G. Giaccone,et al.  Evaluation of KRAS Mutations, Angiogenic Biomarkers, and DCE-MRI in Patients with Advanced Non–Small-Cell Lung Cancer Receiving Sorafenib , 2011, Clinical Cancer Research.

[51]  J. Ardenkjær-Larsen,et al.  Increase in signal-to-noise ratio of > 10,000 times in liquid-state NMR , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[52]  Kimberly L Desmond,et al.  Understanding quantitative pulsed CEST in the presence of MT , 2012, Magnetic resonance in medicine.

[53]  B. Rosen,et al.  High resolution measurement of cerebral blood flow using intravascular tracer bolus passages. Part I: Mathematical approach and statistical analysis , 1996, Magnetic resonance in medicine.

[54]  Thomas Hambrock,et al.  Prostate cancer: multiparametric MR imaging for detection, localization, and staging. , 2011, Radiology.

[55]  R. Pazdur Response rates, survival, and chemotherapy trials. , 2000, Journal of the National Cancer Institute.

[56]  Carmel Hayes,et al.  Prediction of clinicopathologic response of breast cancer to primary chemotherapy at contrast-enhanced MR imaging: initial clinical results. , 2006, Radiology.

[57]  Glyn Johnson,et al.  Low-grade gliomas: dynamic susceptibility-weighted contrast-enhanced perfusion MR imaging--prediction of patient clinical response. , 2006, Radiology.

[58]  A. Miller,et al.  Reporting results of cancer treatment , 1981, Cancer.

[59]  F. Gallagher,et al.  13C MR spectroscopy measurements of glutaminase activity in human hepatocellular carcinoma cells using hyperpolarized 13C‐labeled glutamine , 2008, Magnetic resonance in medicine.

[60]  A. Manduca,et al.  Assessment of hepatic fibrosis with magnetic resonance elastography. , 2007, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[61]  R. Bryant,et al.  The dynamics of water-protein interactions. , 1996, Annual review of biophysics and biomolecular structure.

[62]  J. Ophir,et al.  Elastography: A Quantitative Method for Imaging the Elasticity of Biological Tissues , 1991, Ultrasonic imaging.

[63]  Frederik L. Giesel,et al.  Diagnostic performance of spectroscopic and perfusion MRI for distinction of brain tumors , 2006, Neurology.

[64]  Peter C M van Zijl,et al.  MRI detection of glycogen in vivo by using chemical exchange saturation transfer imaging (glycoCEST) , 2007, Proceedings of the National Academy of Sciences.

[65]  R V Mulkern,et al.  The general solution to the Bloch equation with constant rf and relaxation terms: application to saturation and slice selection. , 1993, Medical physics.

[66]  R. Ehman,et al.  MR elastography of liver tumors: preliminary results. , 2008, AJR. American journal of roentgenology.

[67]  A. Padhani,et al.  Effects of 5,6-dimethylxanthenone-4-acetic acid on human tumor microcirculation assessed by dynamic contrast-enhanced magnetic resonance imaging. , 2002, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[68]  J Alfred Witjes,et al.  Staging prostate cancer with dynamic contrast-enhanced endorectal MR imaging prior to radical prostatectomy: experienced versus less experienced readers. , 2005, Radiology.

[69]  Jinyuan Zhou,et al.  Detection of the Ischemic Penumbra Using pH-Weighted MRI , 2007, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[70]  E. Chekmenev,et al.  Propane-d6 Heterogeneously Hyperpolarized by Parahydrogen , 2014, The journal of physical chemistry. C, Nanomaterials and interfaces.

[71]  Albert P. Chen,et al.  Original contributions Feasibility of using hyperpolarized (1- 13 C)lactate as a substrate for in vivo metabolic 13 C MRSI studies , 2008 .

[72]  C. Jack,et al.  “Palpation of the Brain” Using Magnetic Resonance Elastography , 1999 .

[73]  D. Yablonskiy,et al.  Hyperpolarized 3He and perfluorocarbon gas diffusion MRI of lungs , 2006 .

[74]  John Kurhanewicz,et al.  Analysis of hyperpolarized dynamic 13C lactate imaging in a transgenic mouse model of prostate cancer. , 2010, Magnetic resonance imaging.

[75]  A. Jackson,et al.  Reproducibility of quantitative dynamic contrast-enhanced MRI in newly presenting glioma. , 2003, The British journal of radiology.

[76]  R Sinkus,et al.  Tumour biomechanical response to the vascular disrupting agent ZD6126 in vivo assessed by magnetic resonance elastography , 2014, British Journal of Cancer.

[77]  Robert Rohling,et al.  MR elastography of prostate cancer: quantitative comparison with histopathology and repeatability of methods , 2014, NMR in biomedicine.

[78]  Gary Kelloff,et al.  The Quantitative Imaging Network: NCI's Historical Perspective and Planned Goals. , 2014, Translational oncology.

[79]  L. Schwartz,et al.  Promise and pitfalls of quantitative imaging in oncology clinical trials. , 2012, Magnetic resonance imaging.

[80]  Glyn Johnson,et al.  Glioma grading: sensitivity, specificity, and predictive values of perfusion MR imaging and proton MR spectroscopic imaging compared with conventional MR imaging. , 2003, AJNR. American journal of neuroradiology.

[81]  M. Thaning,et al.  Real-time metabolic imaging. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[82]  Subha Madhavan,et al.  NCI Workshop Report: Clinical and Computational Requirements for Correlating Imaging Phenotypes with Genomics Signatures , 2014, Translational oncology.

[83]  Thomas E Yankeelov,et al.  Clinical utility of quantitative imaging. , 2015, Academic radiology.

[84]  C. Micheel,et al.  COMMITTEE ON QUALIFICATION OF BIOMARKERS AND SURROGATE ENDPOINTS IN CHRONIC DISEASE , 2010 .

[85]  T. Walker,et al.  Spin-exchange optical pumping of noble-gas nuclei , 1997 .

[86]  John Kurhanewicz,et al.  Hyperpolarized [2-13C]-fructose: a hemiketal DNP substrate for in vivo metabolic imaging. , 2009, Journal of the American Chemical Society.

[87]  B. Ross,et al.  Parahydrogen‐induced polarization (PHIP) hyperpolarized MR receptor imaging in vivo: a pilot study of 13C imaging of atheroma in mice , 2011, NMR in biomedicine.

[88]  E. Chekmenev,et al.  Hyperpolarization of “Neat” Liquids by NMR Signal Amplification by Reversible Exchange , 2015, The journal of physical chemistry letters.

[89]  B. Ross,et al.  Real-time molecular imaging of tricarboxylic acid cycle metabolism in vivo by hyperpolarized 1-(13)C diethyl succinate. , 2012, Journal of the American Chemical Society.

[90]  Susan M. Chang,et al.  Comparison of ADC metrics and their association with outcome for patients with newly diagnosed glioblastoma being treated with radiation therapy, temozolomide, erlotinib and bevacizumab , 2014, Journal of Neuro-Oncology.

[91]  Alain Pitiot,et al.  Magnetization transfer phenomenon in the human brain at 7 T , 2010, NeuroImage.

[92]  A. Manduca,et al.  MR elastography of breast cancer: preliminary results. , 2002, AJR. American journal of roentgenology.

[93]  Susumu Mori,et al.  Mechanism of magnetization transfer during on‐resonance water saturation. A new approach to detect mobile proteins, peptides, and lipids , 2003, Magnetic resonance in medicine.

[94]  E. Chekmenev,et al.  Low-field MRI can be more sensitive than high-field MRI. , 2013, Journal of magnetic resonance.

[95]  Cynthia A. Reinhart-King,et al.  Tensional homeostasis and the malignant phenotype. , 2005, Cancer cell.

[96]  M. Okada,et al.  [New response evaluation criteria in solid tumours-revised RECIST guideline (version 1.1)]. , 2009, Gan to kagaku ryoho. Cancer & chemotherapy.

[97]  R. Jain Normalizing tumor microenvironment to treat cancer: bench to bedside to biomarkers. , 2013, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[98]  Sarah E Bohndiek,et al.  Production of hyperpolarized [1,4-13C2]malate from [1,4-13C2]fumarate is a marker of cell necrosis and treatment response in tumors , 2009, Proceedings of the National Academy of Sciences.

[99]  M. Ziol,et al.  Transient elastography: a new noninvasive method for assessment of hepatic fibrosis. , 2003, Ultrasound in medicine & biology.

[100]  M Wintermark,et al.  ASFNR Recommendations for Clinical Performance of MR Dynamic Susceptibility Contrast Perfusion Imaging of the Brain , 2015, American Journal of Neuroradiology.

[101]  Thomas E Yankeelov,et al.  Magnetic resonance in the era of molecular imaging of cancer. , 2011, Magnetic resonance imaging.

[102]  T. Bathen,et al.  Diffusion‐weighted and dynamic contrast‐enhanced MRI in evaluation of early treatment effects during neoadjuvant chemotherapy in breast cancer patients , 2011, Journal of magnetic resonance imaging : JMRI.

[103]  E. Chekmenev,et al.  NMR hyperpolarization techniques for biomedicine. , 2015, Chemistry.

[104]  Jinyuan Zhou,et al.  Using the amide proton signals of intracellular proteins and peptides to detect pH effects in MRI , 2003, Nature Medicine.

[105]  Jinyuan Zhou,et al.  Amide proton transfer imaging of 9L gliosarcoma and human glioblastoma xenografts , 2008, NMR in biomedicine.

[106]  R. Gillies,et al.  Why do cancers have high aerobic glycolysis? , 2004, Nature Reviews Cancer.

[107]  R. Ehman,et al.  Magnetic resonance elastography: A review , 2010, Clinical anatomy.

[108]  Thomas E Yankeelov,et al.  Methods and challenges in quantitative imaging biomarker development. , 2015, Academic radiology.

[109]  B. Naume,et al.  Neoadjuvant chemotherapy in breast cancer-response evaluation and prediction of response to treatment using dynamic contrast-enhanced and diffusion-weighted MR imaging , 2010, European Radiology.

[110]  L. Esserman,et al.  Locally advanced breast cancer: MR imaging for prediction of response to neoadjuvant chemotherapy--results from ACRIN 6657/I-SPY TRIAL. , 2012, Radiology.

[111]  K. Brindle,et al.  Probing Lactate Dehydrogenase Activity in Tumors by Measuring Hydrogen/Deuterium Exchange in Hyperpolarized l-[1-13C,U-2H]Lactate , 2012, Journal of the American Chemical Society.

[112]  William D Rooney,et al.  Potential for differentiation of pseudoprogression from true tumor progression with dynamic susceptibility-weighted contrast-enhanced magnetic resonance imaging using ferumoxytol vs. gadoteridol: a pilot study. , 2011, International journal of radiation oncology, biology, physics.

[113]  Thomas E Yankeelov,et al.  Predicting the Response of Breast Cancer to Neoadjuvant Therapy Using a Mechanically Coupled Reaction-Diffusion Model. , 2015, Cancer research.

[114]  S. Patz,et al.  An open-access, very-low-field MRI system for posture-dependent 3He human lung imaging. , 2008, Journal of magnetic resonance.

[115]  F. Kallel,et al.  Elastographic Imaging of the Normal Canine Prostate In Vitro , 1999, Ultrasonic imaging.

[116]  Albert Lai,et al.  Apparent diffusion coefficient histogram analysis stratifies progression-free and overall survival in patients with recurrent GBM treated with bevacizumab: a multi-center study , 2012, Journal of Neuro-Oncology.

[117]  S. Kety The theory and applications of the exchange of inert gas at the lungs and tissues. , 1951, Pharmacological reviews.

[118]  Ron Kikinis,et al.  Variations of dynamic contrast-enhanced magnetic resonance imaging in evaluation of breast cancer therapy response: a multicenter data analysis challenge. , 2014, Translational oncology.

[119]  Hiroto Hatabu,et al.  Human pulmonary imaging and spectroscopy with hyperpolarized 129Xe at 0.2T. , 2008, Academic radiology.

[120]  H. Jóhannesson,et al.  Parahydrogen‐induced polarization in imaging: Subsecond 13C angiography , 2001, Magnetic resonance in medicine.

[121]  A Gregory Sorensen,et al.  Dynamic susceptibility contrast MRI measures of relative cerebral blood volume as a prognostic marker for overall survival in recurrent glioblastoma: results from the ACRIN 6677/RTOG 0625 multicenter trial. , 2015, Neuro-oncology.

[122]  M. Lustig,et al.  Fast dynamic 3D MR spectroscopic imaging with compressed sensing and multiband excitation pulses for hyperpolarized 13C studies , 2011, Magnetic resonance in medicine.

[123]  Wei Chen,et al.  Hyperpolarized 15N-pyridine Derivatives as pH-Sensitive MRI Agents , 2015, Scientific Reports.

[124]  Lorenzo Bonomo,et al.  Diffusion‐weighted Imaging in Evaluating the Response to Neoadjuvant Breast Cancer Treatment , 2011, The breast journal.

[125]  Richard G Abramson,et al.  Pitfalls in RECIST Data Extraction for Clinical Trials: Beyond the Basics. , 2015, Academic radiology.

[126]  E. Chekmenev,et al.  Sub-second proton imaging of 13C hyperpolarized contrast agents in water. , 2014, Contrast media & molecular imaging.

[127]  E. Chekmenev,et al.  Long-lived spin States for low-field hyperpolarized gas MRI. , 2014, Chemistry.

[128]  E F Halpern,et al.  Cerebral blood volume maps of gliomas: comparison with tumor grade and histologic findings. , 1994, Radiology.

[129]  Xavier Golay,et al.  Amide proton transfer imaging of human brain tumors at 3T , 2006, Magnetic resonance in medicine.

[130]  K. Brindle Imaging metabolism with hyperpolarized (13)C-labeled cell substrates. , 2015, Journal of the American Chemical Society.

[131]  R. Wahl,et al.  From RECIST to PERCIST: Evolving Considerations for PET Response Criteria in Solid Tumors , 2009, Journal of Nuclear Medicine.

[132]  J W Belliveau,et al.  Ultrafast imaging of brain tumors , 1993, Topics in magnetic resonance imaging : TMRI.

[133]  Robin L. Jones,et al.  Phase I Trial of Preoperative Chemoradiation plus Sorafenib for High-Risk Extremity Soft Tissue Sarcomas with Dynamic Contrast-Enhanced MRI Correlates , 2013, Clinical Cancer Research.

[134]  Bowers,et al.  Transformation of symmetrization order to nuclear-spin magnetization by chemical reaction and nuclear magnetic resonance. , 1986, Physical review letters.

[135]  Mikko I. Kettunen,et al.  Magnetic resonance imaging of tumor glycolysis using hyperpolarized 13C-labeled glucose , 2013, Nature Medicine.

[136]  J. Gore,et al.  Imaging of amide proton transfer and nuclear Overhauser enhancement in ischemic stroke with corrections for competing effects , 2015, NMR in biomedicine.

[137]  S. Steinberg,et al.  Phase II clinical trial of cediranib in patients with metastatic castration‐resistant prostate cancer , 2013, BJU international.

[138]  Matthew S Rosen,et al.  Near-unity nuclear polarization with an open-source 129Xe hyperpolarizer for NMR and MRI , 2013, Proceedings of the National Academy of Sciences.

[139]  Jinyuan Zhou,et al.  Practical data acquisition method for human brain tumor amide proton transfer (APT) imaging , 2008, Magnetic resonance in medicine.

[140]  François Cornud,et al.  Multiparametric magnetic resonance imaging for the detection and localization of prostate cancer: combination of T2‐weighted, dynamic contrast‐enhanced and diffusion‐weighted imaging , 2011, BJU international.

[141]  Bing Ma,et al.  Multi-Site Clinical Evaluation of DW-MRI as a Treatment Response Metric for Breast Cancer Patients Undergoing Neoadjuvant Chemotherapy , 2015, PloS one.

[142]  Myeong-Jin Kim,et al.  Diffusion and perfusion MRI prediction of progression‐free survival in patients with hepatocellular carcinoma treated with concurrent chemoradiotherapy , 2014, Journal of magnetic resonance imaging : JMRI.

[143]  A. Manduca,et al.  Magnetic resonance elastography by direct visualization of propagating acoustic strain waves. , 1995, Science.

[144]  Thomas E Yankeelov,et al.  Assessing the accuracy and reproducibility of modality independent elastography in a murine model of breast cancer , 2015, Journal of medical imaging.

[145]  Jinyuan Zhou,et al.  In vivo three‐dimensional whole‐brain pulsed steady‐state chemical exchange saturation transfer at 7 T , 2012, Magnetic resonance in medicine.

[146]  Michael I Miga A new approach to elastography using mutual information and finite elements. , 2003, Physics in medicine and biology.

[147]  Thomas E Yankeelov,et al.  A mechanically coupled reaction–diffusion model for predicting the response of breast tumors to neoadjuvant chemotherapy , 2013, Physics in medicine and biology.

[148]  R. Jain,et al.  Losartan inhibits collagen I synthesis and improves the distribution and efficacy of nanotherapeutics in tumors , 2011, Proceedings of the National Academy of Sciences.

[149]  Richard Eisenberg,et al.  Para hydrogen induced polarization in hydrogenation reactions , 1987 .

[150]  Jinyuan Zhou,et al.  Amide proton transfer (APT) contrast for imaging of brain tumors , 2003, Magnetic resonance in medicine.

[151]  Thomas E. Yankeelov,et al.  Quantitative multimodality imaging in cancer research and therapy , 2014, Nature Reviews Clinical Oncology.

[152]  Timothy D Johnson,et al.  Parametric response map as an imaging biomarker to distinguish progression from pseudoprogression in high-grade glioma. , 2010, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[153]  Benjamin M Ellingson,et al.  Longitudinal DSC-MRI for Distinguishing Tumor Recurrence From Pseudoprogression in Patients With a High-grade Glioma , 2017, American journal of clinical oncology.

[154]  R S Balaban,et al.  Detection of proton chemical exchange between metabolites and water in biological tissues. , 1998, Journal of magnetic resonance.

[155]  F. Shellock,et al.  MRI safety update 2008: part 2, screening patients for MRI. , 2008, AJR. American journal of roentgenology.

[156]  P. Larson,et al.  Metabolic Imaging of Patients with Prostate Cancer Using Hyperpolarized [1-13C]Pyruvate , 2013, Science Translational Medicine.