Diffusion-weighted (DW) and dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) for monitoring anticancer therapy

There is an increasing awareness that anatomical approaches based on measurements of tumor size have significant limitations for assessing therapy response. Functional imaging techniques are increasing being used to monitor response to therapies with novel mechanisms of action, often predicting the success of therapy before conventional measurements have changed. Dynamic contrast-enhanced and diffusion magnetic resonance imaging (MRI) are the most advanced in their evidence base, and in this manuscript we focus on them as response parameters. Technology, data gathering methods, and current limitations for these techniques are addressed. With few exceptions, most studies shows that successful treatment is reflected by increases in tumor water diffusion values visible as increased apparent diffusion coefficient values. Most response assessment studies also show that successful treatment results in decreases in tumor vascularization and microvessel permeability.

[1]  J. E. Tanner,et al.  Spin diffusion measurements : spin echoes in the presence of a time-dependent field gradient , 1965 .

[2]  H. Weinmann,et al.  Pharmacokinetics of GdDTPA/dimeglumine after intravenous injection into healthy volunteers. , 1984, Physiological chemistry and physics and medical NMR.

[3]  D. Le Bihan,et al.  Separation of diffusion and perfusion in intravoxel incoherent motion MR imaging. , 1988, Radiology.

[4]  D. Norris,et al.  Biexponential diffusion attenuation in various states of brain tissue: Implications for diffusion‐weighted imaging , 1996, Magnetic resonance in medicine.

[5]  P. Tofts Modeling tracer kinetics in dynamic Gd‐DTPA MR imaging , 1997, Journal of magnetic resonance imaging : JMRI.

[6]  J. Witjes,et al.  Evaluation of chemotherapy in advanced urinary bladder cancer with fast dynamic contrast-enhanced MR imaging. , 1998, Radiology.

[7]  W E Reddick,et al.  Dynamic MR imaging (DEMRI) of microcirculation in bone sarcoma , 1999, Journal of magnetic resonance imaging : JMRI.

[8]  Toshinori Hirai,et al.  Usefulness of diffusion‐weighted MRI with echo‐planar technique in the evaluation of cellularity in gliomas , 1999, Journal of magnetic resonance imaging : JMRI.

[9]  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.

[10]  R. Gonzalez,et al.  Diffusion-weighted MR imaging of the brain. , 2000, Radiology.

[11]  W. Rooney,et al.  Determination of the MRI contrast agent concentration time course in vivo following bolus injection: Effect of equilibrium transcytolemmal water exchange , 2000, Magnetic resonance in medicine.

[12]  Olav Haraldseth,et al.  Measurement of cell density and necrotic fraction in human melanoma xenografts by diffusion weighted magnetic resonance imaging , 2000, Magnetic resonance in medicine.

[13]  P. Ellen Grant,et al.  Diffusion-weighted MR imaging of the brain. , 2000, Radiology.

[14]  R. Edelman,et al.  Semiquantitative assessment of uterine perfusion using first pass dynamic contrast-enhanced MR imaging for patients treated with uterine fibroid embolization. , 2000, Journal of magnetic resonance imaging : JMRI.

[15]  J. Geschwind,et al.  Chemoembolization of liver tumor in a rabbit model: assessment of tumor cell death with diffusion-weighted MR imaging and histologic analysis. , 2000, Journal of vascular and interventional radiology : JVIR.

[16]  Rakesh K. Jain,et al.  Normalizing tumor vasculature with anti-angiogenic therapy: A new paradigm for combination therapy , 2001, Nature Medicine.

[17]  D P Dearnaley,et al.  Effects of androgen deprivation on prostatic morphology and vascular permeability evaluated with mr imaging. , 2001, Radiology.

[18]  C T Moonen,et al.  Diffusion tensor MRI of the human kidney , 2001, Journal of magnetic resonance imaging : JMRI.

[19]  David L Buckley,et al.  Uncertainty in the analysis of tracer kinetics using dynamic contrast‐enhanced T1‐weighted MRI , 2002, Magnetic resonance in medicine.

[20]  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.

[21]  David L Buckley,et al.  Transcytolemmal water exchange and its affect on the determination of contrast agent concentration in vivo , 2002, Magnetic resonance in medicine.

[22]  Jean-Luc Daire,et al.  Evaluation of liver diffusion isotropy and characterization of focal hepatic lesions with two single-shot echo-planar MR imaging sequences: prospective study in 66 patients. , 2003, Radiology.

[23]  Paul A Meyers,et al.  Osteogenic and Ewing sarcomas: estimation of necrotic fraction during induction chemotherapy with dynamic contrast-enhanced MR imaging. , 2003, Radiology.

[24]  K. Hayashi,et al.  Discrimination of metastatic cervical lymph nodes with diffusion-weighted MR imaging in patients with head and neck cancer. , 2003, AJNR. American journal of neuroradiology.

[25]  Stephan E Maier,et al.  Early detection of response to radiation therapy in patients with brain malignancies using conventional and high b-value diffusion-weighted magnetic resonance imaging. , 2003, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[26]  Martin A Lodge,et al.  Combretastatin A4 phosphate has tumor antivascular activity in rat and man as demonstrated by dynamic magnetic resonance imaging. , 2003, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[27]  G. Sevlever,et al.  Characterization of brain tumors by MRS, DWI and Ki-67 labeling index , 2005, Journal of Neuro-Oncology.

[28]  G J M Parker,et al.  Analysis of MR diffusion weighted images. , 2004, The British journal of radiology.

[29]  H. Schlemmer,et al.  Can preoperative contrast-enhanced dynamic MR imaging for prostate cancer predict microvessel density in prostatectomy specimens? , 2004 .

[30]  H. Schlemmer,et al.  Can pre-operative contrast-enhanced dynamic MR imaging for prostate cancer predict microvessel density in prostatectomy specimens? , 2004, European Radiology.

[31]  R. Gillies,et al.  Changes in water mobility measured by diffusion MRI predict response of metastatic breast cancer to chemotherapy. , 2004, Neoplasia.

[32]  A. Padhani,et al.  Perfusion MR Imaging of Extracranial Tumor Angiogenesis , 2004, Topics in magnetic resonance imaging : TMRI.

[33]  J E Husband,et al.  Evaluation of the response to treatment of solid tumours – a consensus statement of the International Cancer Imaging Society , 2004, British Journal of Cancer.

[34]  A. Padhani,et al.  Effects of platinum/taxane based chemotherapy on acute perfusion in human pelvic tumours measured by dynamic MRI , 2005, British Journal of Cancer.

[35]  J R Griffiths,et al.  Clinical studies. , 2005, Advances in pharmacology.

[36]  Benjamin M Yeh,et al.  Dynamic contrast-enhanced magnetic resonance imaging as a pharmacodynamic measure of response after acute dosing of AG-013736, an oral angiogenesis inhibitor, in patients with advanced solid tumors: results from a phase I study. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[37]  Philippe Lambin,et al.  Dynamic contrast-enhanced magnetic resonance imaging of radiation therapy-induced microcirculation changes in rectal cancer. , 2005, International journal of radiation oncology, biology, physics.

[38]  Bradford A Moffat,et al.  Functional diffusion map: a noninvasive MRI biomarker for early stratification of clinical brain tumor response. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[39]  P Kelly Marcom,et al.  Randomized phase III trial of capecitabine compared with bevacizumab plus capecitabine in patients with previously treated metastatic breast cancer. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[40]  Mathias Langer,et al.  Osteosarcoma: Preliminary Results of In Vivo Assessment of Tumor Necrosis After Chemotherapy With Diffusion- and Perfusion-Weighted Magnetic Resonance Imaging , 2006, Investigative radiology.

[41]  Peter Gibbs,et al.  Diffusion changes precede size reduction in neoadjuvant treatment of breast cancer. , 2006, Magnetic resonance imaging.

[42]  I. Wilkinson,et al.  Dexamethasone and Enhancing Solitary Cerebral Mass Lesions: Alterations in Perfusion and Blood-tumor Barrier Kinetics Shown by Magnetic Resonance Imaging , 2006, Neurosurgery.

[43]  Paul Workman,et al.  Minimally invasive pharmacokinetic and pharmacodynamic technologies in hypothesis-testing clinical trials of innovative therapies. , 2006, Journal of the National Cancer Institute.

[44]  T. Hirai,et al.  Monitoring therapeutic responses of primary bone tumors by diffusion-weighted image: initial results , 2006, European Radiology.

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

[46]  T. Hirai,et al.  Diffusion-weighted imaging of metastatic brain tumors: comparison with histologic type and tumor cellularity. , 2006, AJNR. American journal of neuroradiology.

[47]  Ethaar El-Emir,et al.  Combretastatin A-4-phosphate effectively increases tumor retention of the therapeutic antibody, 131I-A5B7, even at doses that are sub-optimal for vascular shut-down. , 2007, International journal of oncology.

[48]  M. Kurrer,et al.  Hodgkin disease: diagnostic value of FDG PET/CT after first-line therapy--is biopsy of FDG-avid lesions still needed? , 2007, Radiology.

[49]  Haesun Choi,et al.  We should desist using RECIST, at least in GIST. , 2007, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[50]  John A Butman,et al.  Validation of dynamic contrast-enhanced magnetic resonance imaging-derived vascular permeability measurements using quantitative autoradiography in the RG2 rat brain tumor model. , 2007, Neoplasia.

[51]  Neil J Sebire,et al.  Tumors in pediatric patients at diffusion-weighted MR imaging: apparent diffusion coefficient and tumor cellularity. , 2007, Radiology.

[52]  B. Ross,et al.  Diffusion magnetic resonance imaging: a biomarker for treatment response in oncology. , 2007, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[53]  T. Yankeelov,et al.  Measuring Tumor Perfusion in Control and Treated Murine Tumors , 2007, Journal of ultrasound in medicine : official journal of the American Institute of Ultrasound in Medicine.

[54]  Tracy T Batchelor,et al.  AZD2171, a pan-VEGF receptor tyrosine kinase inhibitor, normalizes tumor vasculature and alleviates edema in glioblastoma patients. , 2007, Cancer cell.

[55]  Timothy D Johnson,et al.  A feasibility study evaluating the functional diffusion map as a predictive imaging biomarker for detection of treatment response in a patient with metastatic prostate cancer to the bone. , 2007, Neoplasia.

[56]  E. Scurr,et al.  Detection of colorectal hepatic metastases using MnDPDP MR imaging and diffusion-weighted imaging (DWI) alone and in combination , 2008, European Radiology.

[57]  G. Parker,et al.  DCE-MRI biomarkers in the clinical evaluation of antiangiogenic and vascular disrupting agents , 2007, British Journal of Cancer.

[58]  D. Collins,et al.  Dynamic MRI for imaging tumor microvasculature: Comparison of susceptibility and relaxivity techniques in pelvic tumors , 2007, Journal of magnetic resonance imaging : JMRI.

[59]  D J Collins,et al.  Reproducibility of reference tissue quantification of dynamic contrast-enhanced data: comparison with a fixed vascular input function , 2007, Physics in medicine and biology.

[60]  Yutaka Imai,et al.  Relation between cancer cellularity and apparent diffusion coefficient values using diffusion-weighted magnetic resonance imaging in breast cancer , 2008, Radiation Medicine.

[61]  D. Bluemke,et al.  Functional MR imaging assessment of tumor response after 90Y microsphere treatment in patients with unresectable hepatocellular carcinoma. , 2007, Journal of vascular and interventional radiology : JVIR.

[62]  E. Perez,et al.  Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. , 2007, The New England journal of medicine.

[63]  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.

[64]  D. Collins,et al.  Diffusion-weighted MRI in the body: applications and challenges in oncology. , 2007, AJR. American journal of roentgenology.

[65]  Geoff J M Parker,et al.  Imaging Tumor Vascular Heterogeneity and Angiogenesis using Dynamic Contrast-Enhanced Magnetic Resonance Imaging , 2007, Clinical Cancer Research.

[66]  Katsuyuki Nakanishi,et al.  Whole-body MRI for detecting metastatic bone tumor: diagnostic value of diffusion-weighted images. , 2007, Magnetic resonance in medical sciences : MRMS : an official journal of Japan Society of Magnetic Resonance in Medicine.

[67]  L. Shen,et al.  Apparent diffusion coefficient: potential imaging biomarker for prediction and early detection of response to chemotherapy in hepatic metastases. , 2008, Radiology.

[68]  Teresa McShane,et al.  Scan‐rescan variability in perfusion assessment of tumors in MRI using both model and data‐derived arterial input functions , 2008, Journal of magnetic resonance imaging : JMRI.

[69]  D. Mankoff,et al.  Metabolic and vascular features of dynamic contrast-enhanced breast magnetic resonance imaging and (15)O-water positron emission tomography blood flow in breast cancer. , 2008, Academic radiology.

[70]  Timothy D Johnson,et al.  Functional diffusion map as an early imaging biomarker for high-grade glioma: correlation with conventional radiologic response and overall survival. , 2008, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[71]  A. Harris,et al.  A phase I study of combretastatin A4 phosphate (CA4P) and bevacizumab in subjects with advanced solid tumors , 2008 .

[72]  Mark L. Greenberg,et al.  Medical care in long-term survivors of childhood cancer: a report from the childhood cancer survivor study. , 2008, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[73]  W. Scheithauer,et al.  Bevacizumab in Combination With Oxaliplatin-Based Chemotherapy As First-Line Therapy in Metastatic Colorectal Cancer: A Randomized Phase III Study , 2023, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[74]  E. Squillaci,et al.  Malignant renal neoplasms: correlation between ADC values and cellularity in diffusion weighted magnetic resonance imaging at 3 T , 2008, La radiologia medica.

[75]  Michael E Phelps,et al.  Technology Insight: novel imaging of molecular targets is an emerging area crucial to the development of targeted drugs , 2008, Nature Clinical Practice Oncology.

[76]  William E Grizzle,et al.  Breast tumor xenografts: diffusion-weighted MR imaging to assess early therapy with novel apoptosis-inducing anti-DR5 antibody. , 2008, Radiology.

[77]  Andreas Makris,et al.  Early Changes in Functional Dynamic Magnetic Resonance Imaging Predict for Pathologic Response to Neoadjuvant Chemotherapy in Primary Breast Cancer , 2008, Clinical Cancer Research.

[78]  Robert J. Gillies,et al.  Causes and Consequences of Increased Glucose Metabolism of Cancers , 2008, Journal of Nuclear Medicine.

[79]  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.

[80]  M.-Y.L. Su Inflammatory Breast Cancer: Dynamic Contrast-enhanced MR in Patients Receiving Bevacizumab—Initial Experience , 2008 .

[81]  K. Flaherty,et al.  Pilot study of DCE-MRI to predict progression-free survival with sorafenib therapy in renal cell carcinoma , 2008, Cancer biology & therapy.

[82]  Mark W. Dewhirst,et al.  Cycling hypoxia and free radicals regulate angiogenesis and radiotherapy response , 2008, Nature Reviews Cancer.

[83]  David J Collins,et al.  Technology Insight: water diffusion MRI—a potential new biomarker of response to cancer therapy , 2008, Nature Clinical Practice Oncology.

[84]  Geoff J M Parker,et al.  Quantifying Antivascular Effects of Monoclonal Antibodies to Vascular Endothelial Growth Factor: Insights from Imaging , 2009, Clinical Cancer Research.

[85]  M. Schwaiger,et al.  Clinical Applications of FDG PET and PET/CT in Head and Neck Cancer , 2009, Journal of oncology.

[86]  Y. Liu,et al.  Diffusion-Weighted Magnetic Resonance Imaging of Uterine Cervical Cancer , 2009, Journal of computer assisted tomography.

[87]  Evis Sala,et al.  Semiquantitative and quantitative dynamic contrast-enhanced magnetic resonance imaging measurements predict radiation response in cervix cancer. , 2009, International journal of radiation oncology, biology, physics.

[88]  Timothy D Johnson,et al.  The parametric response map is an imaging biomarker for early cancer treatment outcome , 2009, Nature Medicine.

[89]  Gary Liney,et al.  Correlation of diffusion‐weighted magnetic resonance data with cellularity in prostate cancer , 2009, BJU international.

[90]  J E Heiserman,et al.  Relative Cerebral Blood Volume Values to Differentiate High-Grade Glioma Recurrence from Posttreatment Radiation Effect: Direct Correlation between Image-Guided Tissue Histopathology and Localized Dynamic Susceptibility-Weighted Contrast-Enhanced Perfusion MR Imaging Measurements , 2009, American Journal of Neuroradiology.

[91]  H. R. Arvinda,et al.  RETRACTED ARTICLE: Glioma grading: sensitivity, specificity, positive and negative predictive values of diffusion and perfusion imaging , 2009, Journal of Neuro-Oncology.

[92]  Walter H Backes,et al.  Vessel growth and function: depiction with contrast-enhanced MR imaging. , 2009, Radiology.

[93]  P. Choyke,et al.  Diffusion-weighted magnetic resonance imaging as a cancer biomarker: consensus and recommendations. , 2009, Neoplasia.

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

[95]  J. Jesberger,et al.  A Vasculature-Targeting Regimen of Preoperative Docetaxel with or without Bevacizumab for Locally Advanced Breast Cancer: Impact on Angiogenic Biomarkers , 2009, Clinical Cancer Research.

[96]  Bin Wang,et al.  Diffusion‐weighted imaging of prostate cancer: Correlation between apparent diffusion coefficient values and tumor proliferation , 2009, Journal of magnetic resonance imaging : JMRI.

[97]  R. Kauppinen,et al.  Monitoring of gliomas in vivo by diffusion MRI and 1H MRS during gene therapy‐induced apoptosis: interrelationships between water diffusion and mobile lipids , 2009, NMR in biomedicine.

[98]  R. Jain,et al.  Edema control by cediranib, a vascular endothelial growth factor receptor-targeted kinase inhibitor, prolongs survival despite persistent brain tumor growth in mice. , 2009, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[99]  Hon J. Yu,et al.  Residual Breast Cancer Diagnosed by MRI in Patients Receiving Neoadjuvant Chemotherapy with and Without Bevacizumab , 2009, Annals of Surgical Oncology.

[100]  A. Levy,et al.  Focal Liver Lesion Detection and Characterization with Diffusion-weighted MR Imaging: Comparison with Standard Breath-hold T2-weighted Imaging , 2009 .

[101]  Brandon Whitcher,et al.  Quantifying spatial heterogeneity in dynamic contrast‐enhanced MRI parameter maps , 2009, Magnetic resonance in medicine.

[102]  Pt Sutton,et al.  Reproducibility and changes in the apparent diffusion coefficients of solid tumours treated with combretastatin A4 phosphate and bevacizumab in a two-centre phase I clinical trial , 2010 .

[103]  Anwar R. Padhani,et al.  Perfusion MRI in the early clinical development of antivascular drugs: decorations or decision making tools? , 2010, European Journal of Nuclear Medicine and Molecular Imaging.

[104]  Edward Ashton,et al.  Dynamic Contrast-Enhanced Magnetic Resonance Imaging , 2012, Definitions.