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      The Correlation between Apparent Diffusion Coefficient and Tumor Cellularity in Patients: A Meta-Analysis

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          Abstract

          Objective

          To perform a meta-analysis exploring the correlation between the apparent diffusion coefficient (ADC) and tumor cellularity in patients.

          Materials and Methods

          We searched medical and scientific literature databases for studies discussing the correlation between the ADC and tumor cellularity in patients. Only studies that were published in English or Chinese prior to November 2012 were considered for inclusion. Summary correlation coefficient (r) values were extracted from each study, and 95% confidence intervals (CIs) were calculated. Sensitivity and subgroup analyses were performed to investigate potential heterogeneity.

          Results

          Of 189 studies, 28 were included in the meta-analysis, comprising 729 patients. The pooled r for all studies was −0.57 (95% CI: −0.62, −0.52), indicating notable heterogeneity ( P<0.001). After the sensitivity analysis, two studies were excluded, and the pooled r was −0.61 (95% CI: −0.66, −0.56) and was not significantly heterogeneous ( P = 0.127). Regarding tumor type subgroup analysis, there were sufficient data to support a strong negative correlation between the ADC and cellularity for brain tumors. There was no notable evidence of publication bias.

          Conclusions

          There is a strong negative correlation between the ADC and tumor cellularity in patients, particularly in the brain. However, larger, prospective studies are warranted to validate these findings in other cancer types.

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          Most cited references34

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          Meta-DiSc: a software for meta-analysis of test accuracy data

          Background Systematic reviews and meta-analyses of test accuracy studies are increasingly being recognised as central in guiding clinical practice. However, there is currently no dedicated and comprehensive software for meta-analysis of diagnostic data. In this article, we present Meta-DiSc, a Windows-based, user-friendly, freely available (for academic use) software that we have developed, piloted, and validated to perform diagnostic meta-analysis. Results Meta-DiSc a) allows exploration of heterogeneity, with a variety of statistics including chi-square, I-squared and Spearman correlation tests, b) implements meta-regression techniques to explore the relationships between study characteristics and accuracy estimates, c) performs statistical pooling of sensitivities, specificities, likelihood ratios and diagnostic odds ratios using fixed and random effects models, both overall and in subgroups and d) produces high quality figures, including forest plots and summary receiver operating characteristic curves that can be exported for use in manuscripts for publication. All computational algorithms have been validated through comparison with different statistical tools and published meta-analyses. Meta-DiSc has a Graphical User Interface with roll-down menus, dialog boxes, and online help facilities. Conclusion Meta-DiSc is a comprehensive and dedicated test accuracy meta-analysis software. It has already been used and cited in several meta-analyses published in high-ranking journals. The software is publicly available at .
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            Diffusion-weighted magnetic resonance imaging as a cancer biomarker: consensus and recommendations.

            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.
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              Lymphomas and high-grade astrocytomas: comparison of water diffusibility and histologic characteristics.

              To determine if water diffusivity within lymphomas and high-grade astrocytomas correlates with cellularity. Echo-planar diffusion-weighted magnetic resonance (MR) images obtained in 11 patients with brain lymphomas (19 lesions) and in 17 patients with astrocytomas (19 lesions) were retrospectively reviewed. Regions of interest were drawn on apparent diffusion coefficient (ADC) maps in enhancing tumor. ADC values were normalized by dividing ADC values of tumors by those of normal-appearing regions and expressing the quotient as a ratio. Histologic samples from 11 patients with astrocytomas (11 lesions) and seven patients with lymphoma (seven lesions) were reviewed. Cellularity was measured by calculating the percentage of nuclear area and the percentage of cytoplasmic area and expressing the results as the nuclear-to-cytoplasmic (N/C) ratio. The ADC and N/C ratios of both tumor types were compared by using a two-tailed t test. Mean ADC ratio of lymphomas was 1.15 (SD, 0.33; standard error of the mean [SEM], 0.10), and that of high-grade astrocytomas was 1.68 (SD, 0.48; SEM, 0.11) (P <.01). Mean N/C ratio of lymphoma was 1.45 (SD, 0.94; SEM, 0.36), and that of high-grade astrocytomas was 0.24 (SD, 0.18; SEM, 0.05) (P <.01). Measurements of water diffusivity and cellularity suggest that higher cellularity contributes to more restricted diffusion.

                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2013
                11 November 2013
                : 8
                : 11
                : e79008
                Affiliations
                [1 ]Department of Radiology, Southwest Hospital, Third Military Medical University, Chongqing, China
                [2 ]Department of Radiology, Taihu Hospital, Wuxi, China
                [3 ]Department of Administration Office, Yangpu District Center for Disease Control and Prevention, Shanghai, China
                [4 ]Wuxi center for disease control and prevention, Wuxi, Jiangsu, China
                UCSF, United States of America
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: LC ML XH JW. Performed the experiments: LC ML. Analyzed the data: LC ML JB YX JZ LZ XH JW. Contributed reagents/materials/analysis tools: LC ML JB YX XH JW. Wrote the paper: LC ML.

                Article
                PONE-D-12-39029
                10.1371/journal.pone.0079008
                3823989
                24244402
                e5afd8e9-cb1c-4301-aa8d-0cef35c06603
                Copyright @ 2013

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 11 December 2012
                : 18 September 2013
                Page count
                Pages: 9
                Funding
                The authors have no support or funding to report.
                Categories
                Research Article

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