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Objective: To evaluate the performance of six models of population arterial input function (AIF) in the setting of primary breast cancer and neoadjuvant chemotherapy (NAC). The ability to fit patient dynamic contrast-enhanced MRI (DCE-MRI) data, provide physiological plausible data and detect pathological response was assessed., Methods: Quantitative DCE-MRI parameters were calculated for 27 patients at baseline and after 2 cycles of NAC for 6 AIFs. Pathological complete response detection was compared with change in these parameters from a reproduction cohort of 12 patients using the Bland-Altman approach and receiver-operating characteristic analysis., Results: There were fewer fit failures pre-NAC for all models, with the modified Fritz-Hansen having the fewest pre-NAC (3.6%) and post-NAC (18.8%), contrasting with the femoral artery AIF (19.4% and 43.3%, respectively). Median transfer constant values were greatest for the Weinmann function and also showed greatest reductions with treatment (-68%). Reproducibility (r) was the lowest for the Weinmann function (r = -49.7%), with other AIFs ranging from r = -27.8 to -39.2%., Conclusion: Using the best performing AIF is essential to maximize the utility of quantitative DCE-MRI parameters in predicting response to NAC treatment. Applying our criteria, the modified Fritz-Hansen and cosine bolus approximated Parker AIF models performed best. The Fritz-Hansen and biexponential approximated Parker AIFs performed less well, and the Weinmann and femoral artery AIFs are not recommended., Advances in Knowledge: We demonstrate that using the most appropriate AIF can aid successful prediction of response to NAC in breast cancer.

Unlabelled: Imaging techniques play a key role in the management of patients with colorectal cancer. The introduction of new advanced anatomical, functional, and molecular imaging techniques may improve the assessment of diagnosis, prognosis, planning therapy, and assessment of response to treatment of these patients. Functional and molecular imaging techniques in clinical practice may allow the assessment of tumour-specific characteristics and tumour heterogeneity. This paper will review recent developments in imaging technologies and the evolving roles for these techniques in colorectal cancer., Teaching Points: • Imaging techniques play a key role in the management of patients with colorectal cancer. • Advanced imaging techniques improve the evaluation of these patients. • Functional and molecular imaging allows assessment of tumour hallmarks and tumour heterogeneity.

Quantitative whole-body diffusion-weighted MRI (WB-DWI) is now possible using semi-automatic segmentation techniques. The method enables whole-body estimates of global Apparent Diffusion Coefficient (gADC) and total Diffusion Volume (tDV), both of which have demonstrated considerable utility for assessing treatment response in patients with bone metastases from primary prostate and breast cancers. Here we investigate the agreement (inter-observer repeatability) between two radiologists in their definition of Volumes Of Interest (VOIs) and subsequent assessment of tDV and gADC on an exploratory patient cohort of nine. Furthermore, each radiologist was asked to repeat his or her measurements on the same patient data sets one month later to identify the intra-observer repeatability of the technique. Using a Markov Chain Monte Carlo (MCMC) estimation method provided full posterior probabilities of repeatability measures along with maximum a-posteriori values and 95% confidence intervals. Our estimates of the inter-observer Intraclass Correlation Coefficient (ICCinter) for log-tDV and median gADC were 1.00 (0.97-1.00) and 0.99 (0.89-0.99) respectively, indicating excellent observer agreement for these metrics. Mean gADC values were found to have ICCinter = 0.97 (0.81-0.99) indicating a slight sensitivity to outliers in the derived distributions of gADC. Of the higher order gADC statistics, skewness was demonstrated to have good inter-user agreement with ICCinter = 0.99 (0.86-1.00), whereas gADC variance and kurtosis performed relatively poorly: 0.89 (0.39-0.97) and 0.96 (0.69-0.99) respectively. Estimates of intra-observer repeatability (ICCintra) demonstrated similar results: 0.99 (0.95-1.00) for log-tDV, 0.98 (0.89-0.99) and 0.97 (0.83-0.99) for median and mean gADC respectively, 0.64 (0.25-0.88) for gADC variance, 0.85 (0.57-0.95) for gADC skewness and 0.85 (0.57-0.95) for gADC kurtosis. Further investigation of two anomalous patient cases revealed that a very small proportion of voxels with outlying gADC values lead to instability in higher order gADC statistics. We therefore conclude that estimates of median/mean gADC and tumour volume demonstrate excellent inter- and intra-observer repeatability whilst higher order statistics of gADC should be used with caution when ascribing significance to clinical changes.

Cancer therapy is mainly based on different combinations of surgery, radiotherapy, and chemotherapy. Additionally, targeted therapies (designed to disrupt specific tumor hallmarks, such as angiogenesis, metabolism, proliferation, invasiveness, and immune evasion), hormonotherapy, immunotherapy, and interventional techniques have emerged as alternative oncologic treatments. Conventional imaging techniques and current response criteria do not always provide the necessary information regarding therapy success particularly to targeted therapies. In this setting, MR imaging offers an attractive combination of anatomic, physiologic, and molecular information, which may surpass these limitations, and is being increasingly used for therapy response assessment., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Abnormal metabolism is a key tumor hallmark. Proton magnetic resonance spectroscopy (1H-MRS) allows measurement of metabolite concentration that can be utilized to characterize tumor metabolic changes. 1H-MRS measurements of specific metabolites have been implemented in the clinic. This article performs a systematic review of image acquisition and interpretation of 1H-MRS for cancer evaluation, evaluates its strengths and limitations, and correlates metabolite peaks at 1H-MRS with diagnostic and prognostic parameters of cancer in different tumor types.

The bone scan continues to be recommended for both the staging and therapy response assessment of skeletal metastases from prostate cancer. However, it is widely recognised that bone scans have limited sensitivity for disease detection and is both insensitive and non-specific for determining treatment response, at an early enough time point to be clinically useful. We, therefore, review the evolving roles of nuclear medicine and radiology for this application. We have reviewed the published literature reporting recent developments in imaging bone metastases in prostate cancer, and provide a balanced synopsis of the state of the art. The development of single-photon emission computed tomography combined with computed tomography has improved detection sensitivity and specificity but has not yet been shown to lead to improvements in monitoring therapy. A number of bone-specific and tumour-specific tracers for positron emission tomography/computed tomography (PET/CT) are now available for advanced prostate cancer that show promise in both clinical settings. At the same time, the development of whole-body magnetic resonance imaging (WB-MRI) that incorporates diffusion-weighted imaging also offers significant improvements for detection and therapy response assessment. There are emerging data showing comparative SPECT/CT, PET/CT, and WB-MRI test performance for disease detection, but no compelling data on the usefulness of these technologies in response assessment have yet emerged., Competing Interests: Compliance with ethical standards This study does not contain any studies with human or animal subjects performed by any of the authors. Conflict of interest Gary Cook, Gurdip Azad and Anwar Padhani do not have any conflicts of interest.

Technologic advances enable performance of diffusion-weighted imaging (DWI) at ultrahigh b-values, where standard monoexponential model analysis may not apply. Rather, non-Gaussian water diffusion properties emerge, which in cellular tissues are, in part, influenced by the intracellular environment that is not well evaluated by conventional DWI. The novel technique, diffusion kurtosis imaging (DKI), enables characterization of non-Gaussian water diffusion behavior. More advanced mathematical curve fitting of the signal intensity decay curve using the DKI model provides an additional parameter Kapp that presumably reflects heterogeneity and irregularity of cellular microstructure, as well as the amount of interfaces within cellular tissues. Although largely applied for neural applications over the past decade, a small number of studies have recently explored DKI outside the brain. The most investigated organ is the prostate, with preliminary studies suggesting improved tumor detection and grading using DKI. Although still largely in the research phase, DKI is being explored in wider clinical settings. When assessing extracranial applications of DKI, careful attention to details with which body radiologists may currently be unfamiliar is important to ensure reliable results. Accordingly, a robust understanding of DKI is necessary for radiologists to better understand the meaning of DKI-derived metrics in the context of different tumors and how these metrics vary between tumor types and in response to treatment. In this review, we outline DKI principles, propose biostructural basis for observations, provide a comparison with standard monoexponential fitting and the apparent diffusion coefficient, report on extracranial clinical investigations to date, and recommend technical considerations for implementation in body imaging., (© 2015 Wiley Periodicals, Inc.)

Angiogenesis is a key cancer hallmark involved in tumor growth and metastasis development. Angiogenesis and tumor microenvironment significantly influence the response of tumors to therapies. Imaging techniques have changed our understanding of the process of angiogenesis, the resulting vascular performance, and the tumor microenvironment. This article reviews the status and potential clinical value of the imaging modalities used to assess the status of tumor vasculature in vivo, before, during, and after treatment., (Copyright © 2015 Mosby, Inc. All rights reserved.)

Angiogenesis is a key cancer hallmark involved in tumor growth and metastasis development. Tumor angiogenesis is the process whereby new blood vessels are formed to supply nutrients and oxygen to support the growth of tumors. This article reviews the biological basis behind imaging features and the different imaging modalities used to assess the status of tumor neovasculature in vivo at different scales: structural, functional, and molecular., (Copyright © 2015 Mosby, Inc. All rights reserved.)

The first St Gallen Advanced Prostate Cancer Consensus Conference (APCCC) Expert Panel identified and reviewed the available evidence for the ten most important areas of controversy in advanced prostate cancer (APC) management. The successful registration of several drugs for castration-resistant prostate cancer and the recent studies of chemo-hormonal therapy in men with castration-naïve prostate cancer have led to considerable uncertainty as to the best treatment choices, sequence of treatment options and appropriate patient selection. Management recommendations based on expert opinion, and not based on a critical review of the available evidence, are presented. The various recommendations carried differing degrees of support, as reflected in the wording of the article text and in the detailed voting results recorded in supplementary Material, available at Annals of Oncology online. Detailed decisions on treatment as always will involve consideration of disease extent and location, prior treatments, host factors, patient preferences as well as logistical and economic constraints. Inclusion of men with APC in clinical trials should be encouraged., (© The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology.)

Bone is the most common site for breast cancer metastases, occurring in up to 70% of those with metastatic disease. In order to effectively manage these patients, it is essential to have consistent, reproducible and validated methods of assessing response to therapy. We present current clinical practice of imaging response assessment of bone metastases. We also review the biology of bone metastases and measures of response assessment including clinical assessment, tumour markers and imaging techniques; bone scans (BSs), computed tomography (CT), positron emission tomography, magnetic resonance imaging (MRI) and whole-body diffusion-weighted MRI (WB DW-MRI). The current standard of care of BSs and CT has significant limitations and are not routinely recommended for the purpose of response assessment in the bones. WB DW-MRI has the potential to address this unmet need and should be evaluated in clinical trials., (© The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

The use of imaging in the arena of primary treatment for breast cancer is gaining importance as a technique for assessing response to chemotherapy as well as assessing the underlying tumor biology. Both mammography and ultrasound have traditionally been used, in addition to clinical evaluation, to evaluate response to treatment although they have shed little light on the underlying biological processes. Functional magnetic resonance imaging techniques have the ability to assess response to treatments in addition to providing valuable information on changes in tumor perfusion, vascular permeability, oxygenation, cellularity, proliferation, and metabolism both at baseline and after treatment. This noninvasive method of evaluating cellular function is of importance both as endpoints for clinical trials and to our understanding of the biological mechanisms of cancer., (© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Background: This open-label phase I dose-escalation study investigated the safety, efficacy, pharmacokinetics (PK), and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) effects of the oral angiokinase inhibitor nintedanib in patients with advanced solid tumors., Methods: Nintedanib was administered once daily continuously, starting at 100 mg and later amended to allow evaluation of 250 mg b.i.d. The primary endpoint was maximum tolerated dose (MTD). DCE-MRI studies were performed at baseline and on days 2 and 28., Results: Fifty-one patients received nintedanib 100-450 mg once daily (n = 40) or 250 mg b.i.d. (n = 11). Asymptomatic reversible liver enzyme elevations (grade 3) were dose limiting in 2 of 5 patients at 450 mg once daily. At 250 mg b.i.d., 2 of 11 patients experienced dose-limiting toxicity (grade 3 liver enzyme elevation and gastrointestinal symptoms). Common toxicities included fatigue, diarrhea, nausea, vomiting, and abdominal pain (mainly grade ≤2). Among 45 patients, 22 (49%) achieved stable disease; 7 remained on treatment for >6 months. DCE-MRI of target lesions revealed effects in some patients at 200 and ≥400 mg once daily., Conclusion: Nintedanib is well tolerated by patients with advanced solid malignancies, with MTD defined as 250 mg b.i.d., and can induce changes in DCE-MRI. Disease stabilization >6 months was observed in 7 of 51 patients., (©AlphaMed Press; the data published online to support this summary is the property of the authors.)

Purpose: To investigate whether use of multiparametric magnetic resonance (MR) imaging-directed intraoperative frozen-section (IFS) analysis during nerve-sparing robot-assisted radical prostatectomy reduces the rate of positive surgical margins., Materials and Methods: This retrospective analysis of prospectively acquired data was approved by an institutional ethics committee, and the requirement for informed consent was waived. Data were reviewed for 134 patients who underwent preoperative multiparametric MR imaging (T2 weighted, diffusion weighted, and dynamic contrast-material enhanced) and nerve-sparing robot-assisted radical prostatectomy, during which IFS analysis was used, and secondary resections were performed when IFS results were positive for cancer. Control patients (n = 134) matched for age, prostate-specific antigen level, and stage were selected from a pool of 322 patients who underwent nerve-sparing robot-assisted radical prostatectomy without multiparametric MR imaging and IFS analysis. Rates of positive surgical margins were compared by means of the McNemar test, and a multivariate conditional logistic regression model was used to estimate the odds ratio of positive surgical margins for patients who underwent MR imaging and IFS analysis compared with control subjects., Results: Eighteen patients who underwent MR imaging and IFS analysis underwent secondary resections, and 13 of these patients were found to have negative surgical margins at final pathologic examination. Positive surgical margins were found less frequently in the patients who underwent MR imaging and IFS analysis than in control patients (7.5% vs 18.7%, P = .01). When the differences in risk factors are taken into account, patients who underwent MR imaging and IFS had one-seventh the risk of having positive surgical margins relative to control patients (adjusted odds ratio: 0.15; 95% confidence interval: 0.04, 0.61)., Conclusion: The significantly lower rate of positive surgical margins compared with that in control patients provides preliminary evidence of the positive clinical effect of multiparametric MR imaging-directed IFS analysis for patients who undergo prostatectomy., (© RSNA, 2014.)

Purpose: To investigate the optimal distribution of sources using high dose rate brachytherapy to deliver a focal boost to a dominant lesion within the whole prostate gland based on multi-parametric magnetic resonance imaging (mpMRI)., Methods: Sixteen patients with prostate cancer underwent mpMRI each of which demonstrated a dominant lesion. There were single lesions in 6 patients, two lesions in 4 and 3 lesions in 6 patients. Two dosimetric models and parameters were compared in each case. The first model used 10mm intervals between needles, and the second model used additional needles at 5 mm intervals between each needle in the boost area., Results: Three of thirty-two plans did not achieve the plan objectives. These three plans were in the first model. A higher median urethral volume was seen in the 'unsuccessful' group (2.7 cc, and 1.9 cc, respectively, p-value=0.12). Conformity indices of the second model were also better than the first model (COIN index; 0.716 and 0.643, respectively)., Conclusions: Focal monotherapy based on mpMRI achieves optimal dosimetry by individualizing the needle positions using 5mm spacing rather than 10mm spacing within the boost volume. A larger urethral volume may have an adverse effect on this distribution. Formal clinical evaluation of this approach is currently underway., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Quantitative DCE-MRI parameters including K(trans) (transfer constant min(-1)) can predict both response and outcome in breast cancer patients treated with neoadjuvant chemotherapy (NAC). Quantitative methods are time-consuming to calculate, requiring expensive software and interpretive expertise. For diagnostic purposes, signal intensity-time curves (SITCs) are used for tissue characterisation. In this study, we compare the ability of NAC-related changes in SITCs with K(trans) to predict response and outcomes. 73 women with primary breast cancer underwent DCE-MRI studies before and after two cycles of NAC. Patients received anthracycline and/or docetaxel-based chemotherapy. At completion of NAC, patients had local treatment with surgery & radiotherapy and further systemic treatments. SITCs for paired DCE-MRI studies were visually scored using a five-curve type classification schema encompassing wash-in and wash-out phases and correlated with K(trans) values and to the endpoints of pathological response, OS and DFS. 58 paired patients studies were evaluable. The median size by MRI measurement for 52 tumours was 38 mm (range 17-86 mm) at baseline and 26 mm (range 10-85 mm) after two cycles of NAC. Median baseline K(trans) (min(-1)) was 0.214 (range 0.085-0.469), and post-two cycles of NAC was 0.128 (range 0.013-0.603). SITC shapes were significantly related to K(trans) values both before (χ (2) = 43.3, P = 0.000) and after two cycles of NAC (χ (2) = 60.5, P = 0.000). Changes in curve shapes were significantly related to changes in K(trans) (χ (2) = 53.5, P = 0.000). Changes in curve shape were significantly correlated with clinical (P = 0.005) and pathological response (P = 0.005). Reductions in curve shape of ≥1 point were significant for overall improved survival using Kaplan-Meier analysis with a 5-year OS of 80.9 versus 68.6 % (P = 0.048). SITCs require no special software to generate and provide a useful method of assessing the effectiveness of NAC for primary breast cancer.

Current methods of assessing tumor response at skeletal sites with metastatic disease use a combination of imaging tests, serum and urine biochemical markers, and symptoms assessment. These methods do not always enable the positive assessment of therapeutic benefit to be made but instead provide an evaluation of progression, which then guides therapy decisions in the clinic. Functional imaging techniques such as whole-body diffusion magnetic resonance imaging (MRI) when combined with anatomic imaging and other emerging "wet" biomarkers can improve the classification of therapy response in patients with metastatic bone disease. A range of imaging findings can be seen in the clinic depending on the type of therapy and duration of treatment. Successful response to systemic therapy is usually depicted by reductions in signal intensity accompanied by apparent diffusion coefficient (ADC) increases. Rarer patterns of successful treatment include no changes in signal intensity accompanying increases in ADC values (T2 shine-through pattern) or reductions in signal intensity without ADC value changes. Progressive disease results in increases in extent/intensity of disease on high b-value images with variable ADC changes. Diffusion MRI therapy response criteria need to be developed and tested in prospective studies in order to address current, unmet clinical and pharmaceutical needs for reliable measures of tumor response in metastatic bone disease., (Copyright © 2014 Wiley Periodicals, Inc.)

We describe our semi-automatic segmentation of whole-body diffusion-weighted MRI (WBDWI) using a Markov random field (MRF) model to derive tumor total diffusion volume (tDV) and associated global apparent diffusion coefficient (gADC); and demonstrate the feasibility of using these indices for assessing tumor burden and response to treatment in patients with bone metastases. WBDWI was performed on eleven patients diagnosed with bone metastases from breast and prostate cancers before and after anti-cancer therapies. Semi-automatic segmentation incorporating a MRF model was performed in all patients below the C4 vertebra by an experienced radiologist with over eight years of clinical experience in body DWI. Changes in tDV and gADC distributions were compared with overall response determined by all imaging, tumor markers and clinical findings at serial follow up. The segmentation technique was possible in all patients although erroneous volumes of interest were generated in one patient because of poor fat suppression in the pelvis, requiring manual correction. Responding patients showed a larger increase in gADC (median change = +0.18, range = -0.07 to +0.78 × 10(-3) mm2/s) after treatment compared to non-responding patients (median change = -0.02, range = -0.10 to +0.05 × 10(-3) mm2/s, p = 0.05, Mann-Whitney test), whereas non-responding patients showed a significantly larger increase in tDV (median change = +26%, range = +3 to +284%) compared to responding patients (median change = -50%, range = -85 to +27%, p = 0.02, Mann-Whitney test). Semi-automatic segmentation of WBDWI is feasible for metastatic bone disease in this pilot cohort of 11 patients, and could be used to quantify tumor total diffusion volume and median global ADC for assessing response to treatment.

The current pathway for men suspected of having prostate cancer [transrectal biopsy, followed in some cases by magnetic resonance imaging (MRI) for staging] results in over-diagnosis of insignificant tumours, and systematically misses disease in the anterior prostate. Multiparametric MRI has the potential to change this pathway, and if performed before biopsy, might enable the exclusion of significant disease in some men without biopsy, targeted biopsy in others, and improvements in the performance of active surveillance. For the potential benefits to be realized, the setting of standards is vital. This article summarizes the outcome of a meeting of UK radiologists, at which a consensus was achieved on (1) the indications for MRI, (2) the conduct of the scan, (3) a method and template for reporting, and (4) minimum standards for radiologists., (Copyright © 2013 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Objective: This article summarizes the current status of CT perfusion in oncologic imaging, including lesion characterization, staging, prediction of patient outcome or response to therapy, assessment of response to different therapies, and evaluation of tumor relapse. Technical limitations and drawbacks of CT perfusion are also discussed., Conclusion: Tumor angiogenesis is essential for cancer growth and provides an attractive target for oncologic therapies. CT perfusion is an emerging imaging tool that provides both qualitative and quantitative information regarding tumor angiogenesis.

Objective: The purposes of this study were to observe the relation between signal intensity (SI) on MR images with a high b value and the apparent diffusion coefficient (ADC) of bone marrow on body diffusion-weighted MR images, to determine cutoff values that enable separation of malignant and normal bone marrow, and to identify the upper ADC values of untreated multiple myeloma lesions and bone metastatic lesions of breast cancer., Materials and Methods: Retrospective evaluations of 16 patients without bone disease, 21 patients with untreated metastases of breast cancer, and 12 patients with myeloma undergoing body diffusion-weighted MRI were performed (b values, 50 s/mm(2) and 800 or 900 s/mm(2)). Normal yellow and red bone marrow regions were compared with metastatic breast and myeloma bone marrow lesions (one to five regions of interest per patient). SI values were normalized to kidney, muscle, and spinal cord SI. Signal-to-noise ratio and ADC for each lesion were recorded. Nonparametric, receiver operating characteristic, and nonlinear regression analyses were performed., Results: Yellow bone marrow and red bone marrow ADC values were lower than the tumor values (p < 0.001; area under the curve, 0.94; cutoff, 774 μm(2)/s). Tissue-normalized SI and the signal-to-noise ratio of normal bone marrow were also lower than those in tumor regions (p < 0.001; area under the curve, 0.86-0.88). Second-order polynomial curve fitting between SI and ADC was observed (muscle normalized SI, R(2) = 0.4). The 95th percentile and maximum values for mean tumor ADC distribution were 1209 μm(2)/s and 1433 μm(2)/s., Conclusion: Both tissue-normalized SI and ADC measurements allow differentiation between normal bone marrow and tumors of myeloma and breast cancer. The presence of a nonlinear relation between bone marrow SI and ADC values enables definition of an upper limit of ADC value for untreated myeloma lesions and metastatic lesions of breast cancer.

Multiparametric magnetic resonance imaging (mpMRI) is increasingly being used earlier in the prostate cancer diagnostic pathway in order to detect and localize disease. Its results can be used to help decide on the indication, type, and localization of a prostate biopsy for cancer diagnosis. In addition, mpMRI has the potential to contribute information on the characterization, or aggressiveness, of detected cancers including tumor progression over time. There is considerable variation in the way results of different MRI sequences are reported. We conducted a review of scoring systems that have been used in the detection and characterization of prostate cancer. This revealed that existing scoring and reporting systems differ in purpose, scale, and range. We evaluate these differences in this review. This first step in collating all methods of scoring and reporting mpMRI will ultimately lead to consensus approaches to develop a standardized reporting scheme that can be widely adopted and validated to ensure comparability of research outputs and optimal clinical practice., (Copyright © 2012 Wiley Periodicals, Inc.)

Objective: We examine the clinical impetus for whole-body diffusion-weighted MRI and discuss how to implement the technique with clinical MRI systems. We include practical tips and tricks to optimize image quality and reduce artifacts. The interpretative pitfalls are enumerated, and potential challenges are highlighted., Conclusion: Whole-body diffusion-weighted MRI can be used for tumor staging and assessment of treatment response. Meticulous technique and knowledge of potential interpretive pitfalls will help to avoid mistakes and establish this modality in radiologic practice.

Purpose: The vascular disrupting agent (VDA) combretastatin A4 phosphate (CA4P) induces significant tumor necrosis as a single agent. Preclinical models have shown that the addition of an anti-VEGF antibody to a VDA attenuates the revascularization of the surviving tumor rim and thus significantly increases antitumor activity., Experimental Design: Patients with advanced solid malignancies received CA4P at 45, 54, or 63 mg/m(2) on day 1, day 8, and then every 14 days. Bevacizumab 10 mg/kg was given on day 8 and at subsequent cycles four hours after CA4P. Functional imaging with dynamic contrast enhanced-MRI (DCE-MRI) was conducted at baseline, after CA4P alone, and after cycle 1 CA4P + bevacizumab., Results: A total of 63 mg/m(2) CA4P + 10 mg/kg bevacizumab q14 is the recommended phase II dose. A total of 15 patients were enrolled. Dose-limiting toxicities were grade III asymptomatic atrial fibrillation and grade IV liver hemorrhage in a patient with a history of hemorrhage. Most common toxicities were hypertension, headache, lymphopenia, pruritus, and pyrexia. Asymptomatic electrocardiographic changes were seen in five patients. Nine of 14 patients experienced disease stabilization. A patient with ovarian cancer had a CA125 response lasting for more than a year. DCE-MRI showed statistically significant reductions in tumor perfusion/vascular permeability, which reversed after CA4P alone but which were sustained following bevacizumab. Circulating CD34(+) and CD133(+) bone marrow progenitors increased following CA4P as did VEGF and granulocyte colony-stimulating factor levels., Conclusions: CA4P in combination with bevacizumab appears safe and well tolerated in this dosing schedule. CA4P induced profound vascular changes, which were maintained by the presence of bevacizumab., (©2012 AACR.)

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., (Copyright © 2011 Wiley Periodicals, Inc.)

Purpose: To assess the feasibility and reproducibility of 3-tesla diffusion tensor imaging (DTI) of the anal canal., Materials and Methods: DTI was performed in 25 men with no clinical history of anal canal disease undergoing MRI for prostate cancer. Analysis of fractional anisotropy (FA), relative anisotropy (RA), and apparent diffusion coefficient (ADC) were determined for the epithelial/subepithelial layer, internal sphincter, external sphincter, and puborectalis. The directionality of diffusion was recorded from color-coded tractography maps. Obturator internus and gluteus maximus served as reference muscles. Mean (SD) of values for FA, RA, and ADC were compared using analysis of variance. Intra and inter-rater agreement and test reproducibility (n = 5) was assessed by Bland-Altman statistics., Results: Mean (SD) for the epithelial/subepithelial layer, internal, external sphincter, and puborectalis were as follows: FA: 0.283 (0.099); 0.337 (0.049); 0.415 (0.072); and 0.407 (0.062), respectively. RA: 0.241 (0.094); 0.292 (0.050); 0.371 (0.083); 0.361 (0.067), respectively; and ADC: 1.49 (0.23); 1.59 (0.19); 1.51 (0.28); and 1.54 (0.29) × 10(-3) mm(2) /s, respectively. Good overall intra and inter-rater agreement and test-retest reproducibility was noted (coefficient of variation of 4.8-19.4% and 5.9-12.9%, respectively)., Conclusion: Anisotropy is evident in the anal canal with good inter-rater agreement and test reproducibility., (Copyright © 2011 Wiley Periodicals, Inc.)

Purpose: Preclinical studies show that OXi4503 (combretastatin A1 diphosphate, CA1P) is more potent than other clinically evaluated vascular-disrupting agents., Experimental Design: Escalating doses of OXi4503 were given intravenously over 10 minutes on days 1, 8, and 15 every 28 days to patients with advanced solid tumors., Results: Doses were escalated in single-patient cohorts from 0.06 to 1.92 mg/m(2), then expanded cohorts to 15.4 mg/m(2) in 43 patients. Common adverse drug reactions were hypertension, tumor pain, anemia, lymphopenia, and easily controllable nausea/vomiting and fatigue. Five patients experienced different drug-related dose-limiting toxicities, atrial fibrillation, increased troponin, blurred vision, diplopia, and tumor lysis. Prophylactic amlodipine failed to prevent adverse events. Pharmacokinetics showed dose-dependent linear increases in peak plasma concentrations and area under the curve value of OXi4503. One partial response was seen in a heavily pretreated patient with ovarian cancer. Dynamic contrast-enhanced MRI confirmed a dose effect and showed significant antivascular effects in 10 of 13 patients treated at doses of 11 mg/m(2) or higher., Conclusions: The maximum tolerated dose was 8.5 mg/m(2) but escalation to 14 mg/m(2) was possible with only temporary reversible cerebrovascular toxicity by excluding hypertensive patients. As a tumor response was seen at 14 mg/m(2) and maximum tumor perfusion reductions were seen at doses of 11 mg/m(2) or higher, the recommended phase II dose is from 11 to 14 mg/m(2).

Background: The vascular disrupting agent combretastatin-A4-phosphate (CA4P) demonstrated antitumour activity in preclinical studies when combined with radiation., Methods: Patients with non-small-cell lung cancer (NSCLC), prostate adenocarcinoma, and squamous cell carcinoma of the head and neck (SCCHN) received 27 Gy in 6 fractions treating twice weekly over 3 weeks, 55 Gy in 20 fractions over 4 weeks, and 66 Gy in 33 fractions over 6 weeks respectively. CA4P was escalated from 50 mg/m2 to 63 mg/m2. CA4P exposure was further increased from one to three to six doses. Patients with SCCHN received cetuximab in addition., Results: Thirty-nine patients received 121 doses of CA4P. Dose-limiting toxic effects (DLTs) of reversible ataxia and oculomotor nerve palsy occurred in two patients with prostate cancer receiving weekly CA4P at 63 mg/m2. DLT of cardiac ischaemia occurred in two patients with SCCHN at a weekly dose of 50 mg/m2 in combination with cetuximab. Three patients developed grade 3 hypertension. Responses were seen in 7 of 18 patients with NSCLC. At 3 years, 3 of 18 patients with prostate cancer had prostate-specific antigen relapse., Conclusions: Radiotherapy with CA4P appears well tolerated in most patients. The combination of CA4P, cetuximab, and radiotherapy needs further scrutiny before it can be recommended for clinical studies.

Diffusion-weighted (DW) magnetic resonance (MR) imaging is emerging as a powerful clinical tool for directing the care of patients with cancer. Whole-body DW imaging is almost at the stage where it can enter widespread clinical investigations, because the technology is stable and protocols can be implemented for the majority of modern MR imaging systems. There is a continued need for further improvements in data acquisition and analysis and in display technologies. Priority areas for clinical research include clarification of histologic relationships between tissues of interest and DW MR imaging biomarkers at diagnosis and during therapy response. Because whole-body DW imaging excels at bone marrow assessments at diagnosis and for therapy response, it can potentially address a number of unmet clinical and pharmaceutical requirements. There are compelling needs to document and understand how common and novel treatments affect whole-body DW imaging results and to establish response criteria that can be tested in prospective clinical studies that incorporate measures of patient benefit., (© RSNA 2011.)

Targeted therapies are designed to interfere with specific aberrant biologic pathways involved in tumor development. The main classes of novel oncologic drugs include antiangiogenic drugs, antivascular agents, drugs interfering with EGFR-HER2 or KIT receptors, inhibitors of the PI3K/Akt/mTOR pathway, and hormonal therapies. Cancer cells usurp normal signal transduction pathways used by growth factors to stimulate proliferation and sustain viability. The interaction of growth factors with their receptors activates different intracellular pathways affecting key tumor biologic processes such as neoangiogenesis, tumor metabolism, and tumor proliferation. The response of tumors to anticancer therapy can be evaluated with anatomic response assessment, qualitative response assessment, and response assessment with functional and molecular imaging. Angiogenesis can be measured by means of perfusion imaging with computed tomography and magnetic resonance (MR) imaging. Diffusion-weighted MR imaging allows imaging evaluation of tumor cellularity. The main imaging techniques for studying tumor metabolism in vivo are positron emission tomography and MR spectroscopy. Familiarity with imaging findings secondary to tumor response to targeted therapies may help the radiologist better assist the clinician in accurate evaluation of tumor response to these anticancer treatments. Functional and molecular imaging techniques may provide valuable data and augment conventional assessment of tumor response to targeted therapies. Supplemental material available at http://radiographics.rsna.org/lookup/suppl/doi:10.1148/rg.317115108/-/DC1.

Prostate cancer is biologically and clinically a heterogeneous disease which makes imaging evaluation challenging. Magnetic resonance imaging (MRI) has considerable potential to improve prostate cancer detection and characterization. Until recently morphologic MRI has not been routinely incorporated into clinical care because of its limitation to detect, localize and characterize prostate cancer. Performing prostate gland MRI using functional techniques has the potential to provide unique information regarding tumor behavior, including treatment response. In order for multiparametric MRI data to have an impact on patient management, the collected data need to be relayed to clinicians in a standardized way for image construction, analysis and interpretation. This will ensure that patients are treated effectively and in the most appropriate way. Scoring systems similar to those employed successfully for breast imaging need to be developed.

There are no universally accepted methods for assessing tumour response in skeletal sites with metastatic disease; response is assessed by a combination of imaging tests, serum and urine biochemical markers and symptoms assessments. Whole-body diffusion magnetic resonance imaging excels at bone marrow assessments at diagnosis and for therapy evaluations. It can potentially address unmet clinical and pharmaceutical needs for a reliable measure of tumour response. Signal intensity on high b-value images and apparent diffusion coefficient values can be related to underlying biophysical properties of skeletal metastases. Four patterns of change in response to therapy are described this review. Therapy response criteria need to be tested in prospective clinical studies that incorporate conventional measures of patient benefit.

Multifunctional magnetic resonance imaging (MRI) techniques are increasingly being used to address bottlenecks in prostate cancer patient management. These techniques yield qualitative, semi-quantitative and fully quantitative biomarkers that reflect on the underlying biological status of a tumour. If these techniques are to have a role in patient management, then standard methods of data acquisition, analysis and reporting have to be developed. Effective communication by the use of scoring systems, structured reporting and a graphical interface that matches prostate anatomy are key elements. Practical guidelines for integrating multiparametric MRI into clinical practice are presented.

Purpose: To investigate whether early changes in vascular parameters determined with dynamic contrast material-enhanced magnetic resonance (MR) imaging after two cycles of neoadjuvant chemotherapy (NAC) are predictive of disease-free and overall survival in primary breast cancer., Materials and Methods: Institutional ethics approval and informed consent were obtained. Patients with primary breast cancer (median age, 45 years; age range, 22-70 years) recruited from January 2001 to September 2008 underwent dynamic contrast-enhanced MR imaging before and after two cycles of NAC. Quantitative and semiquantitative kinetic parameters were calculated, including the volume transfer constant (K(trans)) and the initial area under the gadolinium concentration-time curve over 60 seconds (IAUGC(60)). Cut points optimized to the receiver operating characteristic curve were used to dichotomize MR imaging data for Kaplan-Meier survival analysis. MR imaging parameters and known prognostic indicators in primary breast cancer were correlated with disease-free and overall survival by using the Cox proportional hazards model for univariate and multivariate analyses., Results: MR imaging was performed before (n = 62) and after (n = 58) two cycles of NAC. The median follow-up time was 43.9 months for disease-free survival and 60.3 months for overall survival. There were 28 recurrences; 26 patients had distant metastases (two had additional local recurrence) and two had local recurrence only. There were 20 deaths, all of which were related to breast cancer. At univariate analysis, progesterone receptor status, the type of surgery performed, higher posttreatment K(trans) (P = .048), and larger posttreatment IAUGC(60) (P = .035) were significant predictors of worse disease-free survival. At multivariate analysis, progesterone receptor status (P = .002) and mean transit time (P = .025) were significant predictors of disease-free survival. Univariate analysis showed that clinical tumor stage (P = .005), progesterone receptor status (P = .025), and type of surgery performed (P = .017) were significant predictors of overall survival. Higher posttreatment K(trans) (P = .043), larger IAUGC(60) (P = .029), and larger tumor size at posttreatment MR imaging were predictive of worse overall survival (P = .018). Of these variables, K(trans) remained an independent indicator of overall survival (P = .038)., Conclusion: Higher posttreatment tumor vascularization as depicted with dynamic contrast-enhanced MR imaging may be associated with higher recurrence and lower survival rates. Dynamic contrast-enhanced MR imaging parameters, in conjunction with traditional prognostic factors, have the potential to be prognostic biomarkers for disease-free and overall survival in primary breast cancer.

Purpose: The antivascular effects of androgen deprivation have been investigated in animal models; however, there has been minimal investigation in human prostate cancer. This study tested the hypothesis that androgen deprivation causes significant reductions in human prostate tumor blood flow and the induction of hypoxia at a magnitude and in a time scale relevant to the neoadjuvant setting before radiotherapy., Methods and Materials: Twenty patients were examined, each with five multi-parameter magnetic resonance imaging scans: two scans before the commencement of androgen suppression, one scan after 1 month of hormone treatment, and two further scans after 3 months of therapy. Quantitative parametric maps of the prostate informing on relative blood flow (rBF), relative blood volume (rBV), vascular permeability (transfer constant [K(trans)]), leakage space (v(e)) and blood oxygenation (intrinsic relaxivity [R(2)∗]) were calculated., Results: Tumor blood volume and blood flow decreased by 83% and 79%, respectively, in the first month (p < 0.0001), with 74% of patients showing significant changes. The proportion of individual patients who achieved significant changes in T1 kinetic parameter values after 3 months of androgen deprivation for tumor measurements was 68% for K(trans) and 53% for v(e) By 3 months, significant increases in R(2)∗ had occurred in prostate tumor, with a rise of 41.1% (p < 0.0001)., Conclusions: Androgen deprivation induces profound vascular collapse within 1 month of starting treatment. Increased R(2)∗ in regions of prostate cancer and a decrease in blood volume suggest a reduction in tumor oxygenation., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Magnetic resonance imaging (MRI) is the mainstay of diagnosis, staging and follow-up of much musculoskeletal pathology. Diffusion-weighted magnetic resonance imaging (DWI) is a recent addition to the MR sequences conventionally employed. DWI provides qualitative and quantitative functional information concerning the microscopic movements of water at the cellular level. A number of musculoskeletal disorders have been evaluated by DWI, including vertebral fractures, bone marrow infection, bone marrow malignancy, primary bone and soft tissue tumours; post-treatment follow-up has also been assessed. Differentiation between benign and malignant vertebral fractures by DWI and monitoring of therapy response have shown excellent results. However, in other pathologies, such as primary soft tissue tumours, DWI data have been inconclusive in some cases, contributing little additional information beyond that gained from conventional MR sequences. The aim of this article is to critically review the current literature on the contribution of DWI to musculoskeletal MRI.

Diffusion-weighted MRI (DW-MRI) is able to detect and characterize tissues because it incorporates sensitivity to water content and water movements into the images that are produced. Compared with other imaging modalities used in oncologic assessments, DW-MRI does not expose patients to ionizing radiations, and no injection of isotopes or any other contrast medium is necessary. Regional or whole-body examinations are possible in reasonably short examination times, allowing DW-MRI to be incorporated into oncologic imaging practice. The information obtained can be quantified and displayed as parametric maps, thus enabling spatial heterogeneity of tissues/tumors to be analyzed. Clinical applications for DW-MRI include lesion detection, characterization, and response assessments. DW-MRI has the potential to direct radiation therapy planning. In the response assessment setting, DW-MRI observations appear to reflect interactions between the mechanism of action of treatments and the underlying structural biology of tissues., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: Multiparametric magnetic resonance imaging (mpMRI) may have a role in detecting clinically significant prostate cancer in men with raised serum prostate-specific antigen levels. Variations in technique and the interpretation of images have contributed to inconsistency in its reported performance characteristics., Objective: Our aim was to make recommendations on a standardised method for the conduct, interpretation, and reporting of prostate mpMRI for prostate cancer detection and localisation., Design, Setting, and Participants: A consensus meeting of 16 European prostate cancer experts was held that followed the UCLA-RAND Appropriateness Method and facilitated by an independent chair., Measurement: Before the meeting, 520 items were scored for "appropriateness" by panel members, discussed face to face, and rescored., Results and Limitations: Agreement was reached in 67% of 260 items related to imaging sequence parameters. T2-weighted, dynamic contrast-enhanced, and diffusion-weighted MRI were the key sequences incorporated into the minimum requirements. Consensus was also reached on 54% of 260 items related to image interpretation and reporting, including features of malignancy on individual sequences. A 5-point scale was agreed on for communicating the probability of malignancy, with a minimum of 16 prostatic regions of interest, to include a pictorial representation of suspicious foci. Limitations relate to consensus methodology. Dominant personalities are known to affect the opinions of the group and were countered by a neutral chairperson., Conclusions: Consensus was reached on a number of areas related to the conduct, interpretation, and reporting of mpMRI for the detection, localisation, and characterisation of prostate cancer. Before optimal dissemination of this technology, these outcomes will require formal validation in prospective trials., (Copyright © 2010 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Functional imaging techniques are increasingly being used to monitor response to therapies, often predicting the success of therapy before conventional measurements are changed. This review focuses on magnetic resonance imaging (MRI) depicted water diffusivity as a tumor response parameter. Response assessments are undertaken by noting changes in signal intensity on high b-value images or by using measurements of apparent diffusion coefficient values. The different diffusion-weighted (DW)-MRI appearances in response to treatment of soft tissue disease and bone metastases are discussed. DW-MRI changes observed in response to cytotoxics, radiotherapy, antiangiogenics, embolization, and thermocoagulation are detailed., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Functional magnetic resonance imaging (MRI) techniques are rapidly gaining importance as methods of exploring the pathophysiological properties of breast carcinomas. In the neoadjuvant setting where the primary tumor remains in situ, functional MRI is able to noninvasively evaluate microenvironmental features such as blood flow and oxygenation. Dynamic contrast-enhanced MRI provides information on tumor vascularity with evidence suggesting a role in predicting response to neoadjuvant chemotherapy. The spatial heterogeneity of response to anti-angiogenic and vascular disrupting agents can also be depicted. There is preliminary data supporting blood oxygenation level-dependent MRI as a potential marker of tumor oxygenation, with the ability to characterize tissue oxygenation changes with neoadjuvant chemotherapy. Additionally, advanced MR sequences such as diffusion-weighted MRI and MR spectroscopy have the potential to provide information relating to cellularity and metabolism, respectively.

Antiangiogenic therapy is a promising approach for the treatment of breast cancer. In practice, however, only a subset of patients who receive antiangiogenic drugs demonstrate a significant response. A key challenge, therefore, is to discover biomarkers that are predictive of response to antiangiogenic therapy. To address this issue, we have designed a window-of-opportunity study in which bevacizumab is administered as a short-term first-line treatment to primary breast cancer patients. Central to our approach is the use of a detailed pharmacodynamic assessment, consisting of pre- and post-bevacizumab multi-parametric magnetic resonance imaging scans and core biopsies for exon array gene expression analysis. Here, we illustrate three intrinsic patterns of response to bevacizumab and discuss the molecular mechanisms that may underpin each. Our results illustrate how the combination of dynamic imaging data and gene expression profiles can guide the development of biomarkers for predicting response to antiangiogenic therapy.

Purpose: To investigate the histopathologic and dynamic magnetic resonance (MR) imaging correlates of intrinsic susceptibility-weighted (ISW) MR imaging in patients with primary human breast adenocarcinoma and to assess the relationship between baseline transverse relaxation rate (R2*) and T2* relaxivity change (ΔR2*) and the response to neoadjuvant chemotherapy (NAC)., Materials and Methods: Institutional ethics approval and informed consent were obtained. Between September 2001 and January 2008, 83 women (median age, 46 years; age range, 26-72 years) with breast cancer were recruited to undergo dynamic contrast medium-enhanced (DCE), dynamic susceptibility contrast-enhanced (DSC), and ISW MR imaging before and after two cycles of NAC. After excluding necrotic, infiltrating, and invasive lobular carcinomas, 31 patients were available for baseline assessment and 27 were available for response assessment. Transfer constant, leakage space, rate constant, initial area under the gadolinium concentration-time curve at 60 seconds, relative blood volume (rBV), relative blood flow (rBF), and R2* were calculated. Relationships between baseline R2* and histopathologic variables (tumor grade, estrogen receptor status, progesterone receptor status, human epidermal growth factor 2 status), tumor size, and dynamic MR imaging parameters were sought. Baseline adenocarcinoma R2* (n = 31) and ΔR2* (n = 27) were correlated with final pathologic response., Results: Inverse correlations between baseline R2* and rBV (ρ = -0.48, P = .013) and rBF (ρ = -0.44, P = .024) were found, but not after NAC. No relationships were observed between baseline R2* and other kinetic imaging parameters, histopathologic characteristics, or tumor size (P > .05). Baseline R2* values were lower in tumors than in normal breast tissue (31.8 sec(-1) vs 36.2 sec(-1), P = .017) but not after NAC. Increases in R2* were observed after treatment (31.1 sec(-1) vs 34.8 sec(-1), P = .006), with larger increases correlating with pathologic response. ΔR2* was not as effective as DCE or DSC MR imaging parameters in the prediction of response., Conclusion: R2* is influenced by blood volume in untreated breast adenocarcinomas. Increases in R2* after two cycles of NAC correlate with pathologic response. Therapy-induced uncoupling of the relationship between R2* and rBV and rBF is consistent with responding tumors becoming hypoxic early during treatment., Supplemental Material: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.10100421/-/DC1., (© RSNA, 2010)

Purpose: To describe the MRI appearances of squamous cell carcinoma of the anal canal before and after chemoradiation and to assess whether MRI features predict for clinical outcome., Methods and Materials: Thirty-five patients (15 male, 20 female; mean age 60.8 years) with histologically proven squamous cell cancer of the anal canal underwent MRI before and 6-8 weeks after definitive chemoradiation. Images were reviewed retrospectively by two radiologists in consensus blinded to clinical outcome: tumor size, signal intensity, extent, and TNM stage were recorded. Following treatment, patients were defined as responders by T and N downstaging and Response Evaluation Criteria in Solid Tumors (RECIST). Final clinical outcome was determined by imaging and case note review: patients were divided into (1) disease-free and (2) with relapse and compared using appropriate univariate methods to identify imaging predictors; statistical significance was at 5%., Results: The majority of tumors were ≤T2 (23/35; 65.7%) and N0 (21/35; 60%), mean size 3.75 cm, and hyperintense (++ to +++, 24/35 patients; 68%). Following chemoradiation, there was a size reduction in all cases (mean 73.3%) and a reduction in signal intensity in 26/35 patients (74.2%). The majority of patients were classified as responders (26/35 (74.2%) patients by T and N downstaging; and 30/35 (85.7%) patients by RECIST). At a median follow-up of 33.5 months, 25 patients (71.4%) remained disease-free; 10 patients (28.6%) had locoregional or metastatic disease. Univariate analysis showed that no individual MRI features were predictive of eventual outcome., Conclusion: Early assessment of response by MRI at 6-8 weeks is unhelpful in predicting future clinical outcome., (Copyright © 2010 Elsevier Inc. All rights reserved.)

There is an increasing opportunity to perform multifunctional imaging at a variety of organ sites with relatively short examination times. Each technique yields quantitative parameters that reflect specific aspects of the underlying tumor or tissue biology. Many biomarkers have emerged that provide unique information on tumor behavior, including response to treatment. The multiparametric approach combines the information from different functional imaging techniques; this goes beyond what can be achieved by using any single functional technique, thus allowing an improved understanding of biologic processes and of responses to therapeutic interventions. Multiparametric imaging has many potential clinical roles; it is useful for pharmaceutical drug development and for predicting therapeutic efficacy.

Introduction: Classically, the first step in the clinical development of drugs in oncology involves assessments of dose limiting toxicity (DLT) and maximum tolerated dose (MTD). New paradigms are needed for antiangiogenic drugs and vascular disrupting agents (VDAs) as they are active at doses well below the MTD and as single agents their use might not translate into anti-tumour efficacy. MRI is able to assess the antivascular effects of antivascular drugs via changes in functional kinetic parameters; however, the usefulness of MRI in decision making has been questioned by many., Objectives: Our aim is to review the experience of using dynamic contrast-enhanced MRI (DCE-MRI) in early clinical development of vascular directed anticancer therapies over the last decade. Thirty-nine phase I and II studies including data on more than 700 patients have been published as abstracts and/or papers, documenting DCE-MRI changes after the administration of antiangiogenic drugs and VDAs., Discussion: Perfusion MRI is helpful in assessing whether mechanistic goals are achieved, in assisting dose selection for phase II studies, in selecting subpopulations enriched for response and in predicting patient benefit. Imaging tools are increasingly available. Future challenges for imaging include correlation with clinical measures of efficacy and determining relationships with blood and serum biomarkers.