Many therapeutic approaches to cancer affect the tumour vasculature, either indirectly or as a direct target. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) has become an important means of investigating this action, both pre-clinically and in early stage clinical trials. For such trials, it is essential that the measurement process (i.e. image acquisition and analysis) can be performed effectively and with consistency among contributing centres. As the technique continues to develop in order to provide potential improvements in sensitivity and physiological relevance, there is considerable scope for between-centre variation in techniques. A workshop was convened by the Imaging Committee of the Experimental Cancer Medicine Centres (ECMC) to review the current status of DCE-MRI and to provide recommendations on how the technique can best be used for early stage trials. This review and the consequent recommendations are summarised here. Key Points • Tumour vascular function is key to tumour development and treatment • Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) can assess tumour vascular function • Thus DCE-MRI with pharmacokinetic models can assess novel treatments • Many recent developments are advancing the accuracy of and information from DCE-MRI • Establishing common methodology across multiple centres is challenging and requires accepted guidelines.

Purpose:To evaluate dynamic contrast-enhanced (DCE) magnetic resonance (MR) imaging for monitoring and assessing treatment response in patients with neuroendocrine liver metastases treated using yttrium 90 ((90)Y)-labeled octreotide ((90)Y-DOTATOC).Materials and Methods:The study was approved by the local research and ethics committee and patient informed consent was obtained. Twenty patients with liver metastases from neuroendocrine tumors underwent T1-weighted DCE MR imaging of the liver before and at 2 months after intravenous (90)Y-DOTATOC treatment. Regions of interest were drawn around target lesions, as well as along liver outlines for each patient. A dual-input single-compartment model was used to compute parameters including fractional distribution volume and the arterial flow fraction. Pre- and posttreatment values were compared using Wilcoxon signed rank test. Treatment response was defined as showing a greater than 50% reduction in the nadir chromogranin A level within the 1st year after treatment. Pretreatment values of responders and nonresponders were compared using the Mann-Whitney test. A two-tailed P value of .008 or less, which accounts for multiple testing, was considered to indicate a significant difference.Results:In responders, tumor and whole liver distribution volume significantly increased after treatment (median tumor distribution volume, 0.182 vs 0.244; median whole liver distribution volume, 0.175 vs 0.207; P =.008). The pretreatment whole liver distribution volume was significantly lower in responders (median, 0.175 vs 0.248; P =.003), while pretreatment tumor arterial flow fraction was significantly higher in responders (median, 1.000 vs 0.761, P =.006).Conclusion:DCE MR imaging may be used to monitor the effects of peptide receptor radiolabeled targeted therapy in patients with neuroendocrine tumors liver metastases; a lower pretreatment distribution volume and high arterial flow fraction was associated with a better response to treatment.© RSNA, 2012.

Objectives: To compare the diagnostic accuracy of gadolinium-ethoxybenzyl-diethylenetriaminepentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI), diffusion-weighted MRI (DW-MRI) and a combination of both techniques for the detection of colorectal hepatic metastases.Methods: 72 patients with suspected colorectal liver metastases underwent Gd-EOB-DTPA MRI and DW-MRI. Images were retrospectively reviewed with unenhanced T(1) and T(2) weighted images as Gd-EOB-DTPA image set, DW-MRI image set and combined image set by two independent radiologists. Each lesion detected was scored for size, location and likelihood of metastasis, and compared with surgery and follow-up imaging. Diagnostic accuracy was compared using receiver operating characteristics and interobserver agreement by kappa statistics.Results: 417 lesions (310 metastases, 107 benign) were found in 72 patients. For both readers, diagnostic accuracy using the combined image set was higher (Az = 0.96, 0.97) than Gd-EOB-DTPA image set (Az = 0.86, 0.89) or DW-MRI image set (Az = 0.93, 0.92). Using combined image set improved identification of liver metastases compared with Gd-EOB-DTPA image set (p<0.001) or DW-MRI image set (p<0.001). There was very good interobserver agreement for lesion classification (κ = 0.81-0.88).Conclusions: Combining DW-MRI with Gd-EOB-DTPA-enhanced T(1) weighted MRI significantly improved the detection of colorectal liver metastases.

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.

N-methanocarbathymidine (N-MCT) has previously been shown to be effective against lethal orthopoxvirus and herpes simplex virus type-1 infections in mice. In this investigation, the antiviral activity of N-MCT was assessed against herpes simplex virus type-2 (HSV-2) in BALB/c mice. BALB/c mice were infected intranasally with a lethal challenge dose of HSV-2. N-MCT was administered orally twice daily to mice using doses of 0.01 to 100 mg/kg to determine effects on survival and on viral replication in organ and central nervous system (CNS) samples. N-MCT provided significant protection from mortality even when treatments were delayed until 3 days after viral infection. Viral replication in organ and CNS samples from N-MCT-treated mice was reduced below the limit of detection after 4 days of treatment. These results indicated that low dose N-MCT treatment was more effective than acyclovir therapy. N-MCT may be effective against HSV disease in humans and is currently undergoing preclinical evaluation. In particular, its potential use as a combination therapy for HSV, with its differing metabolism from acyclovir, make it a promising compound to develop for human use.

PURPOSE To describe computed diffusion weighted (DW) magnetic resonance (MR) imaging as a method for obtaining high-b-value images from DW MR imaging performed at lower b values and to investigate the feasibility of the technique to improve lesion detection in oncologic cases. MATERIALS AND METHODS The study was approved by the institutional and research committee, and written informed consent was obtained from all patients. DW MR imaging was performed on a CuSO(4) phantom at 1.5 T with a range of b values and compared with computed DW MR imaging images synthesized from lower b values (0 and 600 sec/mm(2)). The signal-to-noise ratio (SNR) was compared, and agreement between the SNR of computed DW MR imaging and theoretical estimation assessed. Computed DW MR imaging was evaluated in 10 oncologic patients who underwent whole-body DW MR imaging with b values of 0 and 900 sec/mm(2). Computed DW MR images at computed b values of 1500 and 2000 sec/mm(2) were generated. The image quality and background suppression of acquired and computed images were rated by a radiologist using a four-point scale. The diagnostic performance for malignant lesion detection using these images was evaluated and compared by using the McNemar Test. RESULTS The SNR of computed DW MR imaging of the phantom conformed closely to theoretical predictions. Computed DW MR imaging resulted in a higher SNR compared with acquired DW MR imaging, especially at b values greater than 840 sec/mm(2). In patients, images with a computed b value of 2000 sec/mm(2) produced good image quality and high background suppression (mean scores of 2.8 and 4.0, respectively). Evaluation of images with a computed b value of 2000 sec/mm(2) resulted in higher overall diagnostic sensitivity (96.0%) and specificity (96.6%) compared with images with an acquired b value of 900 sec/mm(2)(sensitivity, 89.4%; specificity, 87.5%; P <.01). CONCLUSION Computed DW MR imaging in the body allows higher-b-value images to be obtained with a good SNR. Clinical computed DW MR imaging is feasible and may improve disease detection. Supplemental material: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.11101919/-/DC1.

PURPOSE To prospectively evaluate apparent diffusion coefficient (ADC) histograms in the prediction of chemotherapy response in patients with metastatic ovarian or primary peritoneal cancer. MATERIALS AND METHODS Research ethics committee approval and patient written informed consent were obtained. Diffusion-weighted (DW) magnetic resonance (MR) imaging was performed through the abdomen and pelvis before and after one and three cycles of chemotherapy in 42 women (mean age, 63.0 years ± 11.4 [standard deviation]) with newly diagnosed or recurrent disease. Reproducibility and intra- and interobserver agreement of ADC calculations were assessed. Per-patient weighted ADC histograms were generated at each time point from pixel ADCs from five or fewer target lesions. Mean ADC, percentiles (10th, 25th, 50th, 75th, 90th), skew, kurtosis, and their change were analyzed according to histologic grade, primary versus recurrent disease status, and response, determined with integrated biochemical and morphologic criteria, with a linear mixed model. Areas under receiver operating characteristic curve (AUCs) for combinations of parameters were calculated with linear discriminant analysis. Results: Coefficients of variation for repeat measurements and for within and between observers were 4.8%, 11.4%, and 13.7%, respectively. Grade and disease status did not significantly affect histogram parameters. Pretreatment ADCs were not predictive of response. In responders, all ADCs increased after the first and third cycle (P <.001), while skew and kurtosis decreased after the third (P <.001 and P =.006, respectively); however, in nonresponders, no parameter changed significantly. Percentage change of the 25th percentile performed best in identifying response (AUC = 0.82 and 0.83 after first and third cycle, respectively), whereas combination of parameters did not improve accuracy. CONCLUSION An early increase of ADCs and later decrease of skew and kurtosis characterize chemotherapy response. Quantitative DW MR imaging can aid in early monitoring of treatment efficacy in patients with advanced ovarian cancer.

AIM To determine the T(2) relaxation time of colorectal hepatic metastases and changes in T(2) relaxation times following chemotherapy. MATERIALS AND METHODS 42 patients with 96 hepatic colorectal metastases underwent baseline MRI. Axial T(1), T(2) and multi-echo GRASE sequences were acquired. ROIs were drawn on T(2) relaxation maps, obtained from GRASE images, encompassing metastasis and normal liver to record T(2) relaxation time values. In 11 patients with 28 metastases, MRI was repeated using same protocol at 6 weeks following chemotherapy. The median pre-treatment T(2) values of metastases and normal liver were compared using the Mann-Whitney test. The pre- and post-treatment median T(2) values of metastases were compared using the Wilcoxon-Rank test for responding (n=16) and non-responding (n=12) lesions defined by RECIST criteria. The change in T(2) values (ΔT(2)) were compared and correlated with percentage change in lesion size. RESULTS There was no difference in the pre-treatment median T(2) of metastases between responding (67.3±8.6) and non-responding metastases (71.4±16.5). At the end of chemotherapy, there was a decrease in the median T(2) of responding lesions (61.6±12.6) p=0.83, and increase in non-responding lesions (76.2±18.4) p=0.03, but these were not significantly different from the pre-treatment values. There was no significant difference in ΔT(2) of responding and non-responding lesions (p=0.18) and no correlation was seen between size change and ΔT(2)(coefficient=0.3). CONCLUSION T(2) relaxation time does not appear to predict response of colorectal liver metastasis to chemotherapy.

OBJECTIVES To determine whether changes in ADC of bone metastases secondary to prostate carcinoma are significantly different in responders compared with progressors on chemotherapy. METHODS Twenty-six patients with known bone metastases secondary to prostate carcinoma underwent diffusion-weighted MRI of the lumbar spine and pelvis at baseline and 12 weeks following chemotherapy. RECIST assessment of staging CT and PSA taken at the same time points were used to classify patients as responders, progressors or stable. ADC (from b = 0,50,100,250,500,750 smm⁻²) and ADC(slow)(from b = 100,250,500,750 smm⁻²) were calculated for up to 5 lesions per patient. RESULTS Mean ADC/ADC(slow) in lesions from responders and progressors showed a significant increase. Although the majority of lesions demonstrated an ADC/ADC(slow) rise, some lesions in both responders and progressors demonstrated a fall in ADC beyond the limits of reproducibility. CONCLUSIONS Mean ADC is not an appropriate measure of response in bone metastases. The heterogeneity of changes in ADC is likely to be related to the composition of bone marrow with changes that have opposing effects on ADC.

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 technique in measuring tissue perfusion is presented and the emerging clinical utility surveyed. The requisites and challenges of quantitative evaluation beyond simple monoexponential relationships are highlighted.