Tumor response assessments with diffusion and perfusion MRI

There is an increasing awareness that the evaluation of tumor response to oncologic treatments based solely on anatomic imaging assessments face many limitations, particularly in this era of novel biologic targeted therapies. Functional imaging techniques such as diffusion‐weighted (DW) and dynamic contrast‐enhanced (DCE) magnetic resonance imaging (MRI) have the ability to depict important tumor biologic features and are able to predict therapy response based on assessments of cellularity and tumor vascularity, which often precede morphologic alterations. In this article we focus on DW‐MRI and DCE‐MRI as response parameters addressing the technologies involved, quantification methods, and validation for each technique and their current role in imaging response to conventional and novel therapies. We also discuss the challenges that lie ahead in the deployment of these imaging methods into the clinical environment. J. Magn. Reson. Imaging 2012;35:745‐763. © 2011 Wiley Periodicals, Inc.

[1]  David S. Martin,et al.  Diffusion and Perfusion Magnetic Resonance Imaging: Applications to Functional MRI , 1996 .

[2]  E. Rostrup,et al.  Measurement of the arterial concentration of Gd‐DTPA using MRI: A step toward quantitative perfusion imaging , 1996, Magnetic resonance in medicine.

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

[4]  P J Drew,et al.  Microvessel density in invasive breast cancer assessed by dynamic gd‐dtpa enhanced MRI , 1997 .

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

[6]  O Salonen,et al.  MRI enhancement and microvascular density in gliomas. Correlation with tumor cell proliferation. , 1999, Investigative radiology.

[7]  Franklyn A. Howe,et al.  Assessment of induced rat mammary tumour response to chemotherapy using the apparent diffusion coefficient of tissue water as determined by diffusion-weighted 1H-NMR spectroscopy in vivo , 1999 .

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

[9]  G Brix,et al.  Pathophysiologic basis of contrast enhancement in breast tumors , 1999, Journal of magnetic resonance imaging : JMRI.

[10]  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.

[11]  H K Lim,et al.  Hepatocellular carcinoma treated with percutaneous radio-frequency ablation: usefulness of power Doppler US with a microbubble contrast agent in evaluating therapeutic response-preliminary results. , 2000, Radiology.

[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]  J P Logue,et al.  Tumour oxygenation levels correlate with dynamic contrast-enhanced magnetic resonance imaging parameters in carcinoma of the cervix. , 2000, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[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]  R. Matsubayashi,et al.  Breast masses with peripheral rim enhancement on dynamic contrast-enhanced MR images: correlation of MR findings with histologic features and expression of growth factors. , 2000, Radiology.

[16]  T. Akashi,et al.  Relationship between bone marrow cellularity and apparent diffusion coefficient , 2001, Journal of magnetic resonance imaging : JMRI.

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

[18]  D Artemov,et al.  Vascular differences detected by MRI for metastatic versus nonmetastatic breast and prostate cancer xenografts. , 2001, Neoplasia.

[19]  H Lyng,et al.  Assessment of tumor oxygenation in human cervical carcinoma by use of dynamic Gd‐DTPA‐enhanced MR imaging , 2001, Journal of magnetic resonance imaging : JMRI.

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

[21]  A. Padhani Dynamic contrast‐enhanced MRI in clinical oncology: Current status and future directions , 2002, Journal of magnetic resonance imaging : JMRI.

[22]  Jan Wolber,et al.  Diffusion MRI for prediction of response of rectal cancer to chemoradiation , 2002, The Lancet.

[23]  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.

[24]  R. Kerbel,et al.  Protracted low-dose effects on human endothelial cell proliferation and survival in vitro reveal a selective antiangiogenic window for various chemotherapeutic drugs. , 2002, Cancer research.

[25]  Donna Richardson,et al.  Tumour necrosis is an independent prognostic marker in non-small cell lung cancer: correlation with biological variables. , 2002, Lung cancer.

[26]  R. Ponzone,et al.  Role of Magnetic Resonance Imaging in the prediction of tumor response in patients with locally advanced breast cancer receiving neoadjuvant chemo-therapy. , 2003, La Radiologia medica.

[27]  Jürgen Griebel,et al.  Tumor microcirculation and diffusion predict therapy outcome for primary rectal carcinoma. , 2003, International journal of radiation oncology, biology, physics.

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

[29]  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.

[30]  Orhan Nalcioglu,et al.  Correlation of dynamic contrast enhancement MRI parameters with microvessel density and VEGF for assessment of angiogenesis in breast cancer , 2003, Journal of magnetic resonance imaging : JMRI.

[31]  S. Maier,et al.  High-b-value diffusion-weighted MR imaging for pretreatment prediction and early monitoring of tumor response to therapy in mice. , 2004, Radiology.

[32]  D. Collins,et al.  Dynamic magnetic resonance imaging of tumor perfusion , 2004, IEEE Engineering in Medicine and Biology Magazine.

[33]  Evaluation of VEGF expression within breast cancer biopsies & tumour microvasculature assessment by multi-functional dynamic contrast-enhanced MRI , 2004 .

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

[35]  C. Boesch,et al.  Diffusion‐weighted imaging of the parotid gland: Influence of the choice of b‐values on the apparent diffusion coefficient value , 2004, Journal of magnetic resonance imaging : JMRI.

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

[37]  An investigation of DCE-MRI as a non-invasive measure of angiogenesis in rectal cancer , 2004 .

[38]  David J Collins,et al.  Dynamic magnetic resonance imaging of tumor perfusion. Approaches and biomedical challenges. , 2004, IEEE engineering in medicine and biology magazine : the quarterly magazine of the Engineering in Medicine & Biology Society.

[39]  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.

[40]  C. Meyer,et al.  Evaluation of the functional diffusion map as an early biomarker of time-to-progression and overall survival in high-grade glioma. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[41]  Y. Ni,et al.  Effect of vascular targeting agent in rat tumor model: dynamic contrast-enhanced versus diffusion-weighted MR imaging. , 2005, Radiology.

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

[43]  Robert J Gillies,et al.  Dynamic contrast-enhanced and diffusion MRI show rapid and dramatic changes in tumor microenvironment in response to inhibition of HIF-1alpha using PX-478. , 2005, Neoplasia.

[44]  Y. Ni,et al.  Diffusion-weighted magnetic resonance imaging allows noninvasive in vivo monitoring of the effects of combretastatin a-4 phosphate after repeated administration. , 2005, Neoplasia.

[45]  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.

[46]  Kevin Camphausen,et al.  Antiangiogenic and antitumor effects of bevacizumab in patients with inflammatory and locally advanced breast cancer. , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[47]  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.

[48]  V. V. van Hinsbergh,et al.  Microtubule-targeting agents inhibit angiogenesis at subtoxic concentrations, a process associated with inhibition of Rac1 and Cdc42 activity and changes in the endothelial cytoskeleton , 2006, Molecular Cancer Therapeutics.

[49]  Frederik De Keyzer,et al.  Extracranial applications of diffusion-weighted magnetic resonance imaging , 2007, European Radiology.

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

[51]  John Suckling,et al.  Informatics in Radiology (infoRAD): Magnetic Resonance Imaging Workbench: analysis and visualization of dynamic contrast-enhanced MR imaging data. , 2006, Radiographics : a review publication of the Radiological Society of North America, Inc.

[52]  A R Padhani,et al.  Diffusion-weighted MRI: a new functional clinical technique for tumour imaging. , 2006, The British journal of radiology.

[53]  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.

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

[55]  D J Collins,et al.  Evaluation of response to treatment using DCE-MRI: the relationship between initial area under the gadolinium curve (IAUGC) and quantitative pharmacokinetic analysis , 2006, Physics in medicine and biology.

[56]  S. Steinberg,et al.  Inflammatory breast cancer: dynamic contrast-enhanced MR in patients receiving bevacizumab--initial experience. , 2007, Radiology.

[57]  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.

[58]  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.

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

[60]  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.

[61]  D. Collins,et al.  Predicting response of colorectal hepatic metastasis: value of pretreatment apparent diffusion coefficients. , 2007, AJR. American journal of roentgenology.

[62]  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.

[63]  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.

[64]  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.

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

[66]  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.

[67]  Robert A. Beckman,et al.  Phase I Evaluation of a Fully Human Anti–αv Integrin Monoclonal Antibody (CNTO 95) in Patients with Advanced Solid Tumors , 2007, Clinical Cancer Research.

[68]  Anwar R. Padhani,et al.  Physiological changes within the prostate caused by androgen withdrawal , 2007 .

[69]  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.

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

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

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

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

[74]  T. Chenevert,et al.  Diffusion magnetic resonance imaging: an imaging treatment response biomarker to chemoradiotherapy in a mouse model of squamous cell cancer of the head and neck. , 2008, Translational oncology.

[75]  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.

[76]  Bernd Hamm,et al.  Diffusion‐weighted magnetic resonance imaging allows monitoring of anticancer treatment effects in patients with soft‐tissue sarcomas , 2008, Journal of magnetic resonance imaging : JMRI.

[77]  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.

[78]  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.

[79]  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.

[80]  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.

[81]  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.

[82]  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.

[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]  Martin O. Leach,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 , 2009, European Radiology.

[85]  Bradford A Moffat,et al.  A feasibility study of parametric response map analysis of diffusion-weighted magnetic resonance imaging scans of head and neck cancer patients for providing early detection of therapeutic efficacy. , 2009, Translational oncology.

[86]  C. Claussen,et al.  Diffusion-weighted MRI of advanced hepatocellular carcinoma during sorafenib treatment: initial results. , 2009, AJR. American journal of roentgenology.

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

[88]  Kevin Harrington,et al.  An exploratory study into the role of dynamic contrast-enhanced magnetic resonance imaging or perfusion computed tomography for detection of intratumoral hypoxia in head-and-neck cancer. , 2009, International journal of radiation oncology, biology, physics.

[89]  T. Mikkelsen,et al.  Imaging response criteria for recurrent gliomas treated with bevacizumab: Role of diffusion weighted imaging as an imaging biomarker , 2010, Journal of Neuro-Oncology.

[90]  L. Schwartz,et al.  New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). , 2009, European journal of cancer.

[91]  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.

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

[93]  Yanlei Li,et al.  Diffusion-weighted imaging in predicting and monitoring the response of uterine cervical cancer to combined chemoradiation. , 2009, Clinical radiology.

[94]  David A Bluemke,et al.  Unresectable hepatocellular carcinoma: serial early vascular and cellular changes after transarterial chemoembolization as detected with MR imaging. , 2009, Radiology.

[95]  U. Sharma,et al.  Longitudinal study of the assessment by MRI and diffusion‐weighted imaging of tumor response in patients with locally advanced breast cancer undergoing neoadjuvant chemotherapy , 2009, NMR in biomedicine.

[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]  T. Hirai,et al.  The value of diffusion-weighted imaging for monitoring the chemotherapeutic response of osteosarcoma: a comparison between average apparent diffusion coefficient and minimum apparent diffusion coefficient , 2010, Skeletal Radiology.

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

[100]  J. Machan,et al.  Diffusion-weighted MRI of peripheral zone prostate cancer: comparison of tumor apparent diffusion coefficient with Gleason score and percentage of tumor on core biopsy. , 2010, AJR. American journal of roentgenology.

[101]  G. Parker,et al.  Identification of early predictive imaging biomarkers and their relationship to serological angiogenic markers in patients with ovarian cancer with residual disease following cytotoxic therapy. , 2010, Annals of oncology : official journal of the European Society for Medical Oncology.

[102]  Woo Kyung Moon,et al.  Diffusion-weighted MR imaging: pretreatment prediction of response to neoadjuvant chemotherapy in patients with breast cancer. , 2010, Radiology.

[103]  Thomas Benner,et al.  Phase II study of cediranib, an oral pan-vascular endothelial growth factor receptor tyrosine kinase inhibitor, in patients with recurrent glioblastoma. , 2010, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[104]  B. Fallone,et al.  Monitoring T2 and ADC at 9.4 T following fractionated external beam radiation therapy in a mouse model , 2010, Physics in medicine and biology.

[105]  Susan M. Chang,et al.  Updated response assessment criteria for high-grade gliomas: response assessment in neuro-oncology working group. , 2010, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[106]  C. Koch,et al.  Early detection of radiation therapy response in non‐Hodgkin's lymphoma xenografts by in vivo 1H magnetic resonance spectroscopy and imaging , 2010, NMR in biomedicine.

[107]  Lei Tang,et al.  Locally advanced rectal carcinoma treated with preoperative chemotherapy and radiation therapy: preliminary analysis of diffusion-weighted MR imaging for early detection of tumor histopathologic downstaging. , 2010, Radiology.

[108]  Brian D Ross,et al.  Predicting and monitoring cancer treatment response with diffusion‐weighted MRI , 2010, Journal of magnetic resonance imaging : JMRI.

[109]  A. Padhani,et al.  Multiparametric imaging of tumor response to therapy. , 2010, Radiology.

[110]  Y. Kajiya,et al.  FDG PET/CT and diffusion-weighted imaging for breast cancer: prognostic value of maximum standardized uptake values and apparent diffusion coefficient values of the primary lesion , 2010, European Journal of Nuclear Medicine and Molecular Imaging.

[111]  N. deSouza,et al.  Diffusion Weighted Magnetic Resonance Imaging of metastatic bone disease: A biomarker for treatment response monitoring. , 2010, Cancer biomarkers : section A of Disease markers.

[112]  P. LaViolette,et al.  Validation of functional diffusion maps (fDMs) as a biomarker for human glioma cellularity , 2010, Journal of magnetic resonance imaging : JMRI.

[113]  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.

[114]  H. Goldschmidt,et al.  Diffusion‐weighted imaging for non‐invasive and quantitative monitoring of bone marrow infiltration in patients with monoclonal plasma cell disease: a comparative study with histology , 2011, British journal of haematology.

[115]  Baris Turkbey,et al.  Is apparent diffusion coefficient associated with clinical risk scores for prostate cancers that are visible on 3-T MR images? , 2011, Radiology.

[116]  Andreas Makris,et al.  Use of dynamic contrast-enhanced MR imaging to predict survival in patients with primary breast cancer undergoing neoadjuvant chemotherapy. , 2011, Radiology.

[117]  A. Maia,et al.  Diffusion MR imaging for monitoring treatment response. , 2011, Neuroimaging clinics of North America.