Cancer organoids to model therapy response: Cancer organoids are miniature, three-dimensional cell culture models that can be made from primary patient tumors and studied in the laboratory. Vlachogiannis et al. asked whether such “tumor-in-a-dish” approaches can be used to predict drug responses in the clinic. They generated a live organoid biobank from patients with metastatic gastrointestinal cancer who had previously been enrolled in phase I or II clinical trials. This allowed the authors to compare organoid drug responses with how the patient actually responded in the clinic. Encouragingly, the organoids had similar molecular profiles to those of the patient tumor, reinforcing their value as a platform for drug screening and development. Science , this issue p. 920

On May 3, 2008, a National Cancer Institute (NCI)-sponsored open consensus conference was held in Toronto, Ontario, Canada, during the 2008 International Society for Magnetic Resonance in Medicine Meeting. Approximately 100 experts and stakeholders summarized the current understanding of diffusion-weighted magnetic resonance imaging (DW-MRI) and reached consensus on the use of DW-MRI as a cancer imaging biomarker. DW-MRI should be tested as an imaging biomarker in the context of well-defined clinical trials, by adding DW-MRI to existing NCI-sponsored trials, particularly those with tissue sampling or survival indicators. Where possible, DW-MRI measurements should be compared with histologic indices including cellularity and tissue response. There is a need for tissue equivalent diffusivity phantoms; meanwhile, simple fluid-filled phantoms should be used. Monoexponential assessments of apparent diffusion coefficient values should use two b values (>100 and between 500 and 1000 mm2/sec depending on the application). Free breathing with multiple acquisitions is superior to complex gating techniques. Baseline patient reproducibility studies should be part of study designs. Both region of interest and histogram analysis of apparent diffusion coefficient measurements should be obtained. Standards for measurement, analysis, and display are needed. Annotated data from validation studies (along with outcome measures) should be made publicly available. Magnetic resonance imaging vendors should be engaged in this process. The NCI should establish a task force of experts (physicists, radiologists, and oncologists) to plan, organize technical aspects, and conduct pilot trials. The American College of Radiology Imaging Network infrastructure may be suitable for these purposes. There is an extraordinary opportunity for DW-MRI to evolve into a clinically valuable imaging tool, potentially important for drug development.

OBJECTIVE. In this article, we present the basic principles of diffusion-weighted imaging (DWI) that can aid radiologists in the qualitative and quantitative interpretation of DW images. However, a detailed discussion of the physics of DWI is beyond the scope of this article. A short discussion ensues on the technical aspects of performing DWI in the body. The emerging applications of DWI for tumor detection, tumor characterization, distinguishing tumor tissue from nontumor tissue, and monitoring and predicting treatment response are highlighted. The challenges to widespread adoption of the technique for cancer imaging in the body are discussed.CONCLUSION. DWI derives its image contrast from differences in the motion of water molecules between tissues. Such imaging can be performed quickly without the need for the administration of exogenous contrast medium. The technique yields qualitative and quantitative information that reflects changes at a cellular level and provides unique insights about tumor cell...

Imaging biomarkers (IBs) are used extensively in drug development and cancer research, but important differences exist between IBs and biospecimen-derived biomarkers. A tailored 'roadmap' is required for the development of new IBs to be used either in clinical research or for decision-making in healthcare. In this Consensus statement, a group of experts assembled by CRUK and the EORTC present 14 key recommendations for accelerating the clinical translation of IBs. Imaging biomarkers (IBs) are integral to the routine management of patients with cancer. IBs used daily in oncology include clinical TNM stage, objective response and left ventricular ejection fraction. Other CT, MRI, PET and ultrasonography biomarkers are used extensively in cancer research and drug development. New IBs need to be established either as useful tools for testing research hypotheses in clinical trials and research studies, or as clinical decision-making tools for use in healthcare, by crossing 'translational gaps' through validation and qualification. Important differences exist between IBs and biospecimen-derived biomarkers and, therefore, the development of IBs requires a tailored 'roadmap'. Recognizing this need, Cancer Research UK (CRUK) and the European Organisation for Research and Treatment of Cancer (EORTC) assembled experts to review, debate and summarize the challenges of IB validation and qualification. This consensus group has produced 14 key recommendations for accelerating the clinical translation of IBs, which highlight the role of parallel (rather than sequential) tracks of technical (assay) validation, biological/clinical validation and assessment of cost-effectiveness; the need for IB standardization and accreditation systems; the need to continually revisit IB precision; an alternative framework for biological/clinical validation of IBs; and the essential requirements for multicentre studies to qualify IBs for clinical use.

Magnetic resonance (MR) imaging plays an increasingly important role in the evaluation of patients with liver disease because of its high contrast resolution, lack of ionizing radiation, and the possibility of performing functional imaging sequences. With advances in hardware and coil systems, diffusion-weighted (DW) MR imaging can now be applied to liver imaging with improved image quality. DW MR imaging enables qualitative and quantitative assessment of tissue diffusivity (apparent diffusion coefficient) without the use of gadolinium chelates, which makes it a highly attractive technique, particularly in patients with severe renal dysfunction at risk for nephrogenic systemic fibrosis. In this review, acquisition parameters, postprocessing, and quantification methods applied to liver DW MR imaging will be discussed. The current clinical uses of DW MR imaging (liver lesion detection and characterization, compared and combined with conventional sequences) and the emerging applications of DW MR imaging (tumor treatment response and diagnosis of liver fibrosis and cirrhosis) will be reviewed. Also, limitations, mainly image quality and reproducibility of diffusion parameters, and future directions of liver DW MR imaging will be discussed.

OBJECTIVE. Diffusion-weighted MRI is increasingly applied in the body. It has been recognized for some time, on the basis of scientific experiments and studies in the brain, that the calculation of apparent diffusion coefficient by simple monoexponential relationship between MRI signal and b value does not fully account for tissue behavior. However, appreciation of this fact in body diffusion MRI is relatively new, because technologic advancements have only recently enabled high-quality body diffusion-weighted images to be acquired using multiple b values. There is now increasing interest in the radiologic community to apply more sophisticated analytic approaches, such as those based on the principles of intravoxel incoherent motion, which allows quantitative parameters that reflect tissue microcapillary perfusion and tissue diffusivity to be derived. CONCLUSION. In this review, we discuss the principles of intravoxel incoherent motion as applied to body diffusion-weighted MRI. The evidence for the techni...