Search

Introduction: Whole body magnetic resonance imaging (WB-MRI) may be more efficient in staging cancers, but can be harder for patients to tolerate. We examined predictors of patient preference for WB-MRI vs. CT/ PET-CT for staging colorectal or lung cancer., Methods: Patients recruited prospectively to two multicentre trials comparing diagnostic accuracy of WB-MRI with standard staging scans were sent two questionnaires: the first, administered at trial registration, captured demographics, educational level and comorbidities; the second, administered after staging completion, measured emotional distress (GHQ-12), positive mood (PANAS), perceived scan burden, patients' beliefs about WB-MRI, and preference for either WB-MRI or CT (colorectal trial), WB-MRI or PET-CT (lung trial). Preference for WB-MRI or CT/ PET-CT was analysed using logistic regression., Results: Baseline and post-staging questionnaires were completed by 97 and 107 patients, respectively. Overall, 56/107 (52%) preferred WB-MRI over standard scans and were more likely to have no additional comorbidities, higher positive mood, greater awareness of potential benefits of WB-MRI and lower levels of perceived WB-MRI scan burden. In adjusted analyses, only awareness of potential WB-MRI benefits remained a significant predictor (OR: 1.516, 95% CIs 1.006-2.284, P = 0.047). Knowledge that WB-MRI does not use radiation predicted preference (adjusted OR: 3.018, 95% CIs 1.099-8.288, P = 0.032), although only 45/107 (42%) patients were aware of this attribute., Conclusions: A small majority of patients undergoing staging of colorectal or lung cancer prefer WB-MRI to CT/ PET-CT. Raising awareness of the potential benefits of WB-MRI, notably lack of ionizing radiation, could influence preference., (© 2020 The Authors. Journal of Medical Imaging and Radiation Oncology published by John Wiley & Sons Australia, Ltd on behalf of Royal Australian and New Zealand College of Radiologists.)

Background: Whole-body magnetic resonance imaging is advocated as an alternative to standard pathways for staging cancer., Objectives: The objectives were to compare diagnostic accuracy, efficiency, patient acceptability, observer variability and cost-effectiveness of whole-body magnetic resonance imaging and standard pathways in staging newly diagnosed non-small-cell lung cancer (Streamline L) and colorectal cancer (Streamline C)., Design: The design was a prospective multicentre cohort study., Setting: The setting was 16 NHS hospitals., Participants: Consecutive patients aged ≥ 18 years with histologically proven or suspected colorectal (Streamline C) or non-small-cell lung cancer (Streamline L)., Interventions: Whole-body magnetic resonance imaging. Standard staging investigations (e.g. computed tomography and positron emission tomography-computed tomography)., Reference Standard: Consensus panel decision using 12-month follow-up data., Main Outcome Measures: The primary outcome was per-patient sensitivity difference between whole-body magnetic resonance imaging and standard staging pathways for metastasis. Secondary outcomes included differences in specificity, the nature of the first major treatment decision, time and number of tests to complete staging, patient experience and cost-effectiveness., Results: Streamline C - 299 participants were included. Per-patient sensitivity for metastatic disease was 67% (95% confidence interval 56% to 78%) and 63% (95% confidence interval 51% to 74%) for whole-body magnetic resonance imaging and standard pathways, respectively, a difference in sensitivity of 4% (95% confidence interval -5% to 13%; p  = 0.51). Specificity was 95% (95% confidence interval 92% to 97%) and 93% (95% confidence interval 90% to 96%) respectively, a difference of 2% (95% confidence interval -2% to 6%). Pathway treatment decisions agreed with the multidisciplinary team treatment decision in 96% and 95% of cases, respectively, a difference of 1% (95% confidence interval -2% to 4%). Time for staging was 8 days (95% confidence interval 6 to 9 days) and 13 days (95% confidence interval 11 to 15 days) for whole-body magnetic resonance imaging and standard pathways, respectively, a difference of 5 days (95% confidence interval 3 to 7 days). The whole-body magnetic resonance imaging pathway was cheaper than the standard staging pathway: £216 (95% confidence interval £211 to £221) versus £285 (95% confidence interval £260 to £310). Streamline L - 187 participants were included. Per-patient sensitivity for metastatic disease was 50% (95% confidence interval 37% to 63%) and 54% (95% confidence interval 41% to 67%) for whole-body magnetic resonance imaging and standard pathways, respectively, a difference in sensitivity of 4% (95% confidence interval -7% to 15%; p  = 0.73). Specificity was 93% (95% confidence interval 88% to 96%) and 95% (95% confidence interval 91% to 98%), respectively, a difference of 2% (95% confidence interval -2% to 7%). Pathway treatment decisions agreed with the multidisciplinary team treatment decision in 98% and 99% of cases, respectively, a difference of 1% (95% confidence interval -2% to 4%). Time for staging was 13 days (95% confidence interval 12 to 14 days) and 19 days (95% confidence interval 17 to 21 days) for whole-body magnetic resonance imaging and standard pathways, respectively, a difference of 6 days (95% confidence interval 4 to 8 days). The whole-body magnetic resonance imaging pathway was cheaper than the standard staging pathway: £317 (95% confidence interval £273 to £361) versus £620 (95% confidence interval £574 to £666). Participants generally found whole-body magnetic resonance imaging more burdensome than standard imaging but most participants preferred the whole-body magnetic resonance imaging staging pathway if it reduced time to staging and/or number of tests., Limitations: Whole-body magnetic resonance imaging was interpreted by practitioners blinded to other clinical data, which may not fully reflect how it is used in clinical practice., Conclusions: In colorectal and non-small-cell lung cancer, the whole-body magnetic resonance imaging staging pathway has similar accuracy to standard staging pathways, is generally preferred by patients, improves staging efficiency and has lower staging costs. Future work should address the utility of whole-body magnetic resonance imaging for treatment response assessment., Trial Registration: Current Controlled Trials ISRCTN43958015 and ISRCTN50436483., Funding: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol. 23, No. 66. See the NIHR Journals Library website for further project information., Competing Interests: Stuart A Taylor reports personal fees from Robarts Clinical Trials Inc. (London, ON, Canada) outside the submitted work. Andrea Rockall reports personal fees from Guerbet (Paris, France) outside the submitted work. Vicky Goh and Anwar Padhani report grants from Siemens AG (Erlangen, Germany) outside the submitted work. Steve Halligan reports non-financial support from iCad Inc. (Nashua, NH, USA) outside the submitted work and was a member of the Health Technology Assessment (HTA) commissioning board (2008–14). Stephen Morris declares past membership of the National Institute for Health Research (NIHR) HTA Clinical Evaluation and Trials Board (2007–9), HTA Commissioning Board (2009–13), Public Health Research Board (2011–17), Health Services and Delivery Research (HSDR) Commissioning Board (2014–16) and HSDR Board (2014–18), and current membership of the NIHR Programme Grants for Applied Research expert subpanel (2015–present) and HSDR Evidence Synthesis Sub Board (2016–present).

Objectives: To investigate whether adaptive statistical iterative reconstruction (ASIR), a hybrid iterative CT image reconstruction algorithm, affects radiomics feature quantification in primary colorectal cancer compared to filtered back projection. Additionally, to establish whether radiomics from single-slice analysis undergo greater change than those from multi-slice analysis., Methods: Following review board approval, contrast-enhanced CT studies from 32 prospective primary colorectal cancer patients were reconstructed with 20% ASIR level increments, from 0 to 100%. Radiomics analysis was applied to single-slice and multi-slice regions of interest outlining the tumour: 70 features, including statistical (first-, second- and high-order) and fractal radiomics, were generated per dataset. The effect of ASIR was calculated by means of multilevel linear regression., Results: Twenty-eight CT datasets were suitable for analysis. Incremental ASIR levels determined a significant change (p < 0.001) in most statistical radiomics features, best described by a simple linear relationship. First-order statistical features, including mean, standard deviation, skewness, kurtosis, energy and entropy, underwent a relatively small change in both single-slice and multi-slice analysis (median standardised effect size B = 0.08). Second-order statistical features, including grey-level co-occurrence and difference matrices, underwent a greater change in single-slice analysis (median B = 0.36) than in multi-slice analysis (median B = 0.13). Fractal features underwent a significant change only in single-slice analysis (median B = 0.49)., Conclusions: Incremental levels of ASIR affect significantly CT radiomics quantification in primary colorectal cancer. Second-order statistical and fractal features derived from single-slice analysis undergo greater change than those from multi-slice analysis., Key Points: • Incremental levels of ASIR determine a significant change in most statistical (first-, second- and high-order) CT radiomics features measured in primary colorectal cancer, best described by a linear relationship. • First-order statistical features undergo a small change, both from single-slice and multi-slice radiomics analyses. • Most second-order statistical features undergo a greater change in single-slice analysis than in multi-slice analysis. Fractal features are only affected in single-slice analysis.

Objectives: To determine the importance placed by patients on attributes associated with whole-body MRI (WB-MRI) and standard cancer staging pathways and ascertain drivers of preference., Methods: Patients recruited to two multi-centre diagnostic accuracy trials comparing WB-MRI with standard staging pathways in lung and colorectal cancer were invited to complete a discrete choice experiment (DCE), choosing between a series of alternate pathways in which 6 attributes (accuracy, time to diagnosis, scan duration, whole-body enclosure, radiation exposure, total scan number) were varied systematically. Data were analysed using a conditional logit regression model and marginal rates of substitution computed. The relative importance of each attribute and probabilities of choosing WB-MRI-based pathways were estimated., Results: A total of 138 patients (mean age 65, 61% male, lung n = 72, colorectal n = 66) participated (May 2015 to September 2016). Lung cancer patients valued time to diagnosis most highly, followed by accuracy, radiation exposure, number of scans, and time in the scanner. Colorectal cancer patients valued accuracy most highly, followed by time to diagnosis, radiation exposure, and number of scans. Patients were willing to wait 0.29 (lung) and 0.45 (colorectal) weeks for a 1% increase in pathway accuracy. Patients preferred WB-MRI-based pathways (probability 0.64 [lung], 0.66 [colorectal]) if they were equivalent in accuracy, total scan number, and time to diagnosis compared with a standard staging pathway., Conclusions: Staging pathways based on first-line WB-MRI are preferred by the majority of patients if they at least match standard pathways for diagnostic accuracy, time to diagnosis, and total scan number., Key Points: • WB-MRI staging pathways are preferred to standard pathways by the majority of patients provided they at least match standard staging pathways for accuracy, total scan number, and time to diagnosis. • For patients with lung cancer, time to diagnosis was the attribute valued most highly, followed by accuracy, radiation dose, number of additional scans, and time in a scanner. Preference for patients with colorectal cancer was similar. • Most (63%) patients were willing to trade attributes, such as faster diagnosis, for improvements in pathway accuracy and reduced radiation exposure.

Background: Whole-body MRI (WB-MRI) could be an alternative to multimodality staging of colorectal cancer, but its diagnostic accuracy, effect on staging times, number of tests needed, cost, and effect on treatment decisions are unknown. We aimed to prospectively compare the diagnostic accuracy and efficiency of WB-MRI-based staging pathways with standard pathways in colorectal cancer., Methods: The Streamline C trial was a prospective, multicentre trial done in 16 hospitals in England. Eligible patients were 18 years or older, with newly diagnosed colorectal cancer. Exclusion criteria were severe systemic disease, pregnancy, contraindications to MRI, or polyp cancer. Patients underwent WB-MRI, the result of which was withheld until standard staging investigations were complete and the first treatment decision made. The multidisciplinary team recorded its treatment decision based on standard investigations, then on the WB-MRI staging pathway (WB-MRI plus additional tests generated), and finally on all tests. The primary outcome was difference in per-patient sensitivity for metastases between standard and WB-MRI staging pathways against a consensus reference standard at 12 months, in the per-protocol population. Secondary outcomes were difference in per-patient specificity for metastatic disease detection between standard and WB-MRI staging pathways, differences in treatment decisions, staging efficiency (time taken, test number, and costs), and per-organ sensitivity and specificity for metastases and per-patient agreement for local T and N stage. This trial is registered with the International Standard Randomised Controlled Trial registry, number ISRCTN43958015, and is complete., Findings: Between March 26, 2013, and Aug 19, 2016, 1020 patients were screened for eligibility. 370 patients were recruited, 299 of whom completed the trial; 68 (23%) had metastasis at baseline. Pathway sensitivity was 67% (95% CI 56 to 78) for WB-MRI and 63% (51 to 74) for standard pathways, a difference in sensitivity of 4% (-5 to 13, p=0·51). No adverse events related to imaging were reported. Specificity did not differ between WB-MRI (95% [95% CI 92-97]) and standard pathways (93% [90-96], p=0·48). Agreement with the multidisciplinary team's final treatment decision was 96% for WB-MRI and 95% for the standard pathway. Time to complete staging was shorter for WB-MRI (median, 8 days [IQR 6-9]) than for the standard pathway (13 days [11-15]); a 5-day (3-7) difference. WB-MRI required fewer tests (median, one [95% CI 1 to 1]) than did standard pathways (two [2 to 2]), a difference of one (1 to 1). Mean per-patient staging costs were £216 (95% CI 211-221) for WB-MRI and £285 (260-310) for standard pathways., Interpretation: WB-MRI staging pathways have similar accuracy to standard pathways and reduce the number of tests needed, staging time, and cost., Funding: UK National Institute for Health Research., (Copyright © 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Purpose: Treatment of metastatic colorectal cancer frequently includes antiangiogenic agents such as bevacizumab. Size measurements are inadequate to assess treatment response to these agents, and newer response assessment criteria are needed. We aimed to evaluate F-FDG PET-derived texture parameters in a preclinical colorectal cancer model as alternative metrics of response to treatment with bevacizumab., Materials and Methods: Fourteen CD1 athymic mice injected in the flank with 5×106 LS174T cells (human colorectal carcinoma) were either untreated controls (n=7) or bevacizumab treated (n=7). After 2 weeks, mice underwent F-FDG PET/CT. Calliper-measured tumor growth (Δvol) and final tumor volume (Volcal), F-FDG PET metabolically active volume (Volmet), mean metabolism (Metmean), and maximum metabolism (Metmax) were measured. Twenty-four texture features were compared between treated and untreated mice. Immunohistochemical mean tumor vascular density was estimated by anti-CD-34 staining after tumor resection., Results: Treated mice had significantly lower tumor vascular density (P=0.032), confirming the antiangiogenic therapeutic effect of bevacizumab. None of the conventional measures were different between the two groups: Δvol (P=0.9), Volcal (P=0.7), Volmet (P=0.28), Metmax (P=0.7), or Metmean (P=0.32). One texture parameter, GLSZM-SZV (visually indicating that the F-FDG PET images of treated mice comprise uniformly sized clusters of different activity) had significantly different means between the two groups of mice (P=0.001)., Conclusion: F-FDG PET derived texture parameters, particularly GLSZM-SZV, may be valid biomarkers of tumor response to treatment with bevacizumab, before change in volume.

Background and Aims: Rapid and accurate cancer staging following diagnosis underpins patient management, in particular the identification of distant metastatic disease. Current staging guidelines recommend sequential deployment of various imaging platforms such as computerised tomography (CT) and positron emission tomography (PET) which can be time and resource intensive and onerous for patients. Recent studies demonstrate that whole body magnetic resonance Imaging (WB-MRI) may stage cancer efficiently in a single visit, with potentially greater accuracy than current staging investigations. The Streamline trials aim to evaluate whether WB-MRI increases per patient detection of metastases in non-small cell lung and colorectal cancer compared to standard staging pathways., Methods: The Streamline trials are multicentre, non-randomised, single-arm, prospective diagnostic accuracy studies with a novel design to capture patient management decisions during staging pathways. The two trials recruit adult patients with proven or highly suspected new diagnosis of primary colorectal (Streamline C) or non-small cell lung cancer (Streamline L) referred for staging. Patients undergo WB-MRI in addition to standard staging investigations. Strict blinding protocols are enforced for those interpreting the imaging. A first major treatment decision is made by the multi-disciplinary team prior to WB-MRI revelation based on standard staging investigations only, then based on the WB-MRI and any additional tests precipitated by WB-MRI, and finally based on all available test results. The reference standard is derived by a multidisciplinary consensus panel who assess 12 months of follow-up data to adjudicate on the TNM stage at diagnosis. Health psychology assessment of patients' experiences of the cancer staging pathway will be undertaken via interviews and questionnaires. A cost (effectiveness) analysis of WB-MRI compared to standard staging pathways will be performed., Discussion: We describe a novel approach to radiologist and clinician blinding to ascertain the 'true' diagnostic accuracy of differing imaging pathways and discuss our approach to assessing the impact of WB-MRI on clinical decision making in real-time. The Streamline trials will compare WB-MRI and standard imaging pathways in the same patients, thereby informing the most accurate and efficient approach to staging., Trial Registration: Streamline C ISRCTN43958015 (registered 25/7/2012). Streamline L ISRCTN50436483 (registered 31/7/2012).

Dynamic contrast-enhanced (DCE) images can be acquired at multiple time points and multiple slice locations of a tumor. Image segmentation and registration are important preprocessing steps that can improve subsequent analysis of DCE images by kinetic modeling. An automatic system for region-of-interest segmentation and registration of DCE images is presented. Tissue segmentation is performed using a combination of thresholding and morphological operations, and further refined using shape information from consecutive images. The segmented regions are subsequently registered based on a mutual information method that accounts for possible tissue movement between slices. The proposed segmentation and registration methods are applied on actual DCE CT datasets to illustrate feasibility of practical implementation in the clinic.

Objectives: To assess the cross-centre consistency of iodine enhancement, contrast-to-noise ratio and radiation dose in a multicentre perfusion CT trial of colorectal cancer., Materials and Methods: A cylindrical water phantom containing different iodine inserts was examined on seven CT models in 13 hospitals. The relationship between CT number (Hounsfield units, HU) and iodine concentration (milligrams per millilitre) was established and contrast-to-noise ratios (CNRs) calculated. Radiation doses (CTDIvol, DLP) were compared across all sites., Results: There was a linear relationship between CT number and iodine density. Iodine enhancement varied by a factor of at most 1.10, and image noise by at most 1.5 across the study sites. At an iodine concentration of 1 mg ml(-1) and 100 kV, CNRs ranged from 3.6 to 4.8 in the 220-mm phantom and from 1.4 to 1.9 in the 300-mm phantom. Doses varied by a factor of at most 2.4, but remained within study dose constraints. Iterative reconstruction algorithms did not alter iodine enhancement but resulted in reduced image noise by a factor of at most 2.2, allowing a potential dose decrease of at most 80% compared to filtered back projection (FBP)., Conclusions: Quality control of CT performance across centres indicates that CNR values remain relatively consistent across all sites, giving acceptable image quality within the agreed dose constraints., Key Points: Quality control is essential in a multicentre setting to enable CT quantification. CNRs in a body-sized phantom had the recommended value of at least 1.5. CTDIs and DLPs varied by factors of 1.8 and 2.4 respectively.

Methods: Thirty patients with proven colorectal cancer prospectively underwent integrated 18F-FDG PET/DCE-CT to assess the metabolic-flow phenotype. Both CT blood flow parametric maps and PET images were analyzed. Correlations between PET heterogeneity and perfusion CT were assessed by Spearman's rank correlation analysis., Results: Blood flow visualization provided by DCE-CT images was significantly correlated with 18F-FDG PET metabolically active tumor volume as well as with uptake heterogeneity for patients with stage III/IV tumors (|ρ|:0.66 to 0.78; p-value<0.02)., Conclusion: The positive correlation found with tumor blood flow indicates that intra-tumor heterogeneity of 18F-FDG PET accumulation reflects to some extent tracer distribution and consequently indicates that 18F-FDG PET intra-tumor heterogeneity may be associated with physiological processes such as tumor vascularization.

Unlabelled: This study explores the potential for multifunctional imaging to provide a signature for V-KI-RAS2 Kirsten rat sarcoma viral oncogene homolog (KRAS) gene mutations in colorectal cancer., Methods: This prospective study approved by the institutional review board comprised 33 patients undergoing PET/CT before surgery for proven primary colorectal cancer. Tumor tissue was examined histologically for presence of the KRAS mutations and for expression of hypoxia-inducible factor-1 (HIF-1) and minichromosome maintenance protein 2 (mcm2). The following imaging parameters were derived for each tumor: (18)F-FDG uptake ((18)F-FDG maximum standardized uptake value [SUVmax]), CT texture (expressed as mean of positive pixels [MPP]), and blood flow measured by dynamic contrast-enhanced CT. A recursive decision tree was developed in which the imaging investigations were applied sequentially to identify tumors with KRAS mutations. Monte Carlo analysis provided mean values and 95% confidence intervals for sensitivity, specificity, and accuracy., Results: The final decision tree comprised 4 decision nodes and 5 terminal nodes, 2 of which identified KRAS mutants. The true-positive rate, false-positive rate, and accuracy (95% confidence intervals) of the decision tree were 82.4% (63.9%-93.9%), 0% (0%-10.4%), and 90.1% (79.2%-96.0%), respectively. KRAS mutants with high (18)F-FDG SUVmax and low MPP showed greater frequency of HIF-1 expression (P = 0.032). KRAS mutants with low (18)F-FDG SUV(max), high MPP, and high blood flow expressed mcm2 (P = 0.036)., Conclusion: Multifunctional imaging with PET/CT and recursive decision-tree analysis to combine measurements of tumor (18)F-FDG uptake, CT texture, and perfusion has the potential to identify imaging signatures for colorectal cancers with KRAS mutations exhibiting hypoxic or proliferative phenotypes.

Purpose: To compare four different tracer kinetic models for the analysis of dynamic contrast material-enhanced computed tomographic (CT) data with respect to the prediction of 5-year overall survival in primary colorectal cancer., Materials and Methods: This study was approved by the ethical review board. Archival dynamic contrast-enhanced CT data from 46 patients with colorectal cancer, obtained as part of a research study, were analyzed retrospectively by using the distributed parameter, conventional compartmental, adiabatic tissue homogeneity, and generalized kinetic models. Blood flow, blood volume, mean transit time (MTT), permeability-surface area product, extraction fraction, extravascular extracellular volume (v(e)), and volume transfer constant (K(trans)) were compared by using the Friedman test, with statistical significance at 5%. Following receiver operating characteristic analysis, parameters of the different kinetic models and tumor stage were compared with respect to overall survival discrimination, with use of Kaplan Meier analysis and a univariate Cox proportional hazard model, with additional cross-validation and permutation testing., Results: Blood flow was lower with the distributed parameter model than with the conventional compartmental and adiabatic tissue homogeneity models (P < .0001), and blood flow values determined with the conventional compartmental and adiabatic tissue homogeneity models were similar. Conversely, MTT was longer with the distributed parameter model than with the conventional compartmental and adiabatic tissue homogeneity models (P < .0001). Blood volume, permeability-surface area product, and v(e) were higher with the conventional compartmental model than with the adiabatic tissue homogeneity, distributed parameter, or generalized kinetic models (P < .0001). The extraction fraction was higher with the distributed parameter model than with the adiabatic tissue homogeneity model. With respect to 5-year overall survival, only the distributed parameter model-derived v(e) was predictive of 5-year overall survival with a threshold value of 15.48 mL/100 mL after cross-validation and permutation testing., Conclusion: Parameter values differ significantly between models. Of the models investigated, the distributed parameter model was the best predictor of 5-year overall survival., Supplemental Material: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.12120186/-/DC1., (RSNA, 2013)

Objective: To determine if there is a difference between contrast enhanced CT texture features from the largest cross-sectional area versus the whole tumor, and its effect on clinical outcome prediction., Methods: Entropy (E) and uniformity (U) were derived for different filter values (1.0-2.5: fine to coarse textures) for the largest primary tumor cross-sectional area and the whole tumor of the staging contrast enhanced CT in 55 patients with primary colorectal cancer. Parameters were compared using non-parametric Wilcoxon test. Kaplan-Meier analysis was performed to determine the relationship between CT texture and 5-year overall survival., Results: E was higher and U lower for the whole tumor indicating greater heterogeneity at all filter levels (1.0-2.5): median (range) for E and U for whole tumor versus largest cross-sectional area of 7.89 (7.43-8.31) versus 7.62 (6.94-8.08) and 0.005 (0.004-0.01) versus 0.006 (0.005-0.01) for filter 1.0; 7.88 (7.22-8.48) versus 7.54 (6.86-8.1) and 0.005 (0.003-0.01) versus 0.007 (0.004-0.01) for filter 1.5; 7.88 (7.17-8.54) versus 7.48 (5.84-8.25) and 0.005 (0.003-0.01) versus 0.007 (0.004-0.02) for filter 2.0; and 7.83 (7.03-8.57) versus 7.42 (5.19-8.26) and 0.005 (0.003-0.01) versus 0.006 (0.004-0.03) for filter 2.5 respectively (p ≤ 0.001). Kaplan-Meier analysis demonstrated better separation of E and U for whole tumor analysis for 5-year overall survival., Conclusion: Whole tumor analysis appears more representative of tumor heterogeneity., (Copyright © 2012. Published by Elsevier Ireland Ltd.)

Purpose: To determine if computed tomographic (CT) texture features of primary colorectal cancer are related to 5-year overall survival rate., Materials and Methods: Institutional review board waiver was obtained for this retrospective analysis. Texture features of the entire primary tumor were assessed with contrast material-enhanced staging CT studies obtained in 57 patients as part of an ethically approved study and by using proprietary software. Entropy, uniformity, kurtosis, skewness, and standard deviation of the pixel distribution histogram were derived from CT images without filtration and with filter values corresponding to fine (1.0), medium (1.5, 2.0), and coarse (2.5) textures. Patients were followed up until death and were censored at 5 years if they were still alive. Kaplan-Meier analysis was performed to determine the relationship, if any, between CT texture and 5-year overall survival rate. The Cox proportional hazards model was used to assess independence of texture parameters from stage., Results: Follow-up data were available for 55 of 57 patients. There were eight stage I, 19 stage II, 17 stage III, and 11 stage IV cancers. Fine-texture feature Kaplan-Meier survival plots for entropy, uniformity, kurtosis, skewness, and standard deviation of the pixel distribution histogram were significantly different for tumors above and below each respective threshold receiver operating characteristic (ROC) curve optimal cutoff value (P = .001, P = .018, P = .032, P = .008, and P = .001, respectively), with poorer prognosis for ROC optimal values (a) less than 7.89 for entropy, (b) at least 0.01 for uniformity, (c) less than 2.48 for kurtosis, (d) at least -0.38 for skewness, and (e) less than 61.83 for standard deviation. Multivariate Cox proportional hazards regression analysis showed that each parameter was independent from the stage predictor of overall survival rate (P = .001, P = .009, P = .006, P = .02, and P = .001, respectively)., Conclusion: Fine-texture features are associated with poorer 5-year overall survival rate in patients with primary colorectal cancer., Supplemental Material: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.12120254/-/DC1., (RSNA, 2012)

Objective: The purpose of this article is to assess the effect of observers on combined metabolic-vascular parameters in colorectal cancer., Subjects and Methods: Twenty-five prospective patients (12 men and 13 women; mean age, 66.9 years) with proven primary colorectal adenocarcinoma underwent integrated (18)F-FDG PET/perfusion CT to assess tumor metabolism (mean and maximum standardized uptake value [SUV(mean) and SUV(max), respectively]) and vascularization (blood flow [BF], blood volume [BV], permeability surface-area product, and standardized perfusion value). Intra- and interobserver agreement for PET, perfusion CT, and combined metabolic-flow parameters were determined by Bland-Altman statistics and intraclass correlation coefficients (ICCs)., Results: The mean tumor size was 3.8 ± 1.6 cm; there were five stage IA/B, six stage IIA/B, eight stage IIIA/B, and six stage IV tumors. Intra- and interobserver agreement for individual parameters was fair to good, with mean differences between observers of -0.74 for SUV(max), -0.16 for SUV(mean), 9.72 for BF, 0.15 for BV, -0.76 for permeability surface-area product, and 0.09 for standardized perfusion value. ICCs were 0.44-0.99 and 0.38-0.89 for intra- and interobserver agreement, respectively. Interobserver agreement was variable for combined metabolic-flow parameters but better for metabolic-flow difference than for metabolic-flow ratio: ICCs were 0.69-0.88 for the metabolic-flow difference and 0.44-0.94 for the metabolic-flow ratio., Conclusion: Combined parameters to assess the metabolic-flow relationship are influenced by observer variation. Intra- and interobserver agreement are better for the metabolic-flow differences than for the ratios, suggesting that metabolic-flow differences may be a more robust parameter for clinical practice.

Objectives: To investigate how the histological scoring of microvessel density affects correlations between integrated (18)F-FDG-PET/perfusion CT parameters and CD105 microvessel density., Methods: A total of 53 patients were enrolled from 2007 to 2010. Integrated (18)F-FDG-PET/perfusion CT was successful in 45 patients, 35 of whom underwent surgery without intervening treatment. Tumour SUV(max), SUV(mean) and regional blood flow (BF) were derived. Immunohistochemical staining for CD105 expression and analysis were performed for two hot spots, four hot spots and the Chalkley method. Correlations between metabolic flow parameters and CD105 expression were assessed using Spearman's rank correlation., Results: Mean (SD) for tumour size was 38.5 (20.5) mm, for SUV(max), SUV(mean) and BF it was 19.1 (4.5), 11.6 (2.5) and 85.4 (40.3) mL/min/100 g tissue, and for CD105 microvessel density it was 71.4 (23.6), 66.8 (22.9) and 6.18 (2.07) for two hot spots, four hot spots and the Chalkley method, respectively. Positive correlation between BF and CD105 expression was modest but higher for Chalkley than for four hot spots analysis (r = 0.38, P = 0.03; r = 0.33, P = 0.05, respectively). There were no significant correlations between metabolic parameters (SUV(max) or SUV(mean)) and CD105 expression (r = 0.08-0.22, P = 0.21-0.63)., Conclusions: The histological analysis method affects correlations between tumour CD105 expression and BF but not SUV(max) or SUV(mean)., Key Points: • FDG-PET/perfusion CT offers new surrogate biomarkers of angiogenesis. • Microvessel density scoring influences histopathological correlations with CT blood flow. • Highest correlations were found with the Chalkley analysis method. • Correlations between SUV and CD105 are not affected by the scoring method.

Unlabelled: The aim of this study was to assess the in vivo flow-metabolic phenotype in primary colorectal cancer with integrated (18)F-FDG PET/perfusion CT and its relationship to gold standard histopathologic assessment of angiogenesis and hypoxia., Methods: 45 patients (26 male and 19 female; mean age, 67.6 y) with primary colorectal cancer underwent integrated (18)F-FDG PET/perfusion CT, deriving tumor glucose metabolism (maximum standardized uptake value) and regional blood flow. From this cohort, 35 underwent surgery subsequently, without intervening neoadjuvant treatment, allowing histopathologic correlation with tumor stage, CD105 microvessel density, vascular endothelial growth factor (VEGF), glucose transporter protein 1 (Glut-1), and hypoxia-inducible factor 1 expression., Results: The flow-metabolic ratio was significantly lower for tumors with higher VEGF (3.65 vs. 5.98; P = 0.01) or hypoxia-inducible factor 1 expression (3.63 vs. 5.48; P = 0.04) versus tumors with lower expression. There were significant negative correlations between the tumor flow-metabolic ratio and VEGF expression (r = -0.55, P = 0.0008), indicating that tumors with low blood flow but higher metabolism were associated with higher VEGF expression. Flow and metabolism were coupled in higher-stage (stage III/IV) tumors but not lower-stage tumors (stage I/II) (r = 0.47, P = 0.03, vs. r = 0.09, P = 0.65, respectively., Conclusion: Tumors with a low-flow-high-metabolism phenotype demonstrated higher VEGF expression and may reflect a more angiogenic phenotype.

Objective: To determine how commercial software platform upgrades impact on derived parameters for colorectal cancer., Materials and Methods: Following ethical approval, 30 patients with suspected colorectal cancer underwent Perfusion CT using integrated 64 detector PET/CT before surgery. Analysis was performed using software based on modified distributed parameter analysis (Perfusion software version 4; Perfusion 4.0), then repeated using the previous version (Perfusion software version 3; Perfusion 3.0). Tumour blood flow (BF), blood volume (BV), mean transit time (MTT) and permeability surface area product (PS) were determined for identical regions-of-interest. Slice-by-slice and 'whole tumour' variance was assessed by Bland-Altman analysis., Results: Mean BF, BV and PS was 20.4%, 59.5%, and 106% higher, and MTT 14.3% shorter for Perfusion 4.0 than Perfusion 3.0. The mean difference (95% limits of agreement) were +13.5 (-44.9 to 72.0), +2.61 (-0.06 to 5.28), -1.23 (-6.83 to 4.36), and +14.2 (-4.43 to 32.8) for BF, BV, MTT and PS respectively. Within subject coefficient of variation was 36.6%, 38.0%, 27.4% and 60.6% for BF, BV, MTT and PS respectively indicating moderate to poor agreement., Conclusion: Software version upgrades of the same software platform may result in significantly different parameter values, requiring adjustments for cross-version comparison.

Objective: This article reviews the current and future contributions of functional imaging techniques to improve diagnosis, prognosis, and treatment of colorectal cancer. In addition, evolving roles and challenges for their implementation will be covered., Conclusion: Functional imaging now has a growing role in colorectal cancer. Recent developments in imaging technologies and validation of these newer imaging techniques may lead to significant improvements in the management of patients with colorectal cancer.

The aim was to evaluate the feasibility of fractal analysis for assessing the spatial pattern of colorectal tumour perfusion at dynamic contrast-enhanced CT (perfusion CT). Twenty patients with colorectal adenocarcinoma underwent a 65-s perfusion CT study from which a perfusion parametric map was generated using validated commercial software. The tumour was identified by an experienced radiologist, segmented via thresholding and fractal analysis applied using in-house software: fractal dimension, abundance and lacunarity were assessed for the entire outlined tumour and for selected representative areas within the tumour of low and high perfusion. Comparison was made with ten patients with normal colons, processed in a similar manner, using two-way mixed analysis of variance with statistical significance at the 5% level. Fractal values were higher in cancer than normal colon (p < or = 0.001): mean (SD) 1.71 (0.07) versus 1.61 (0.07) for fractal dimension and 7.82 (0.62) and 6.89 (0.47) for fractal abundance. Fractal values were lower in 'high' than 'low' perfusion areas. Lacunarity curves were shifted to the right for cancer compared with normal colon. In conclusion, colorectal cancer mapped by perfusion CT demonstrates fractal properties. Fractal analysis is feasible, potentially providing a quantitative measure of the spatial pattern of tumour perfusion.

In the past 10 years, overall survival and disease-free survival of patients with colorectal cancer (CRC) has improved substantially because of a combination of factors: (1) more accurate staging as a result of advances in imaging technology; (2) refinements in surgical technique; (3) 'curative' metastasectomy for patients with limited metastatic disease; (4) improvements in radiation therapy planning and greater precision of radiation therapy delivery; and (5) increasing chemotherapeutic options, including antiangiogenic and vascular targeting drugs. In this era of 'personalized medicine', the increasingly individualized treatment of patients with CRC has highlighted the need for functional imaging techniques in addition to conventional anatomic-based imaging. This review discusses the contribution of positron emission tomography to the clinical management of CRC. In addition, evolving techniques such as dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), DCE computed tomography (perfusion CT), diffusion-weighted MRI, and blood oxygenation level-dependent MRI that might have a future role will be covered.

We aimed to determine whether perfusion CT measurements at colorectal cancer staging may predict for subsequent metastatic relapse. Fifty two prospective patients underwent perfusion CT at staging to estimate tumour blood flow, blood volume, mean transit time, and permeability surface area product. Patients considered metastasis free and suitable for surgery underwent curative resection subsequently. At final analysis, a median of 48.6 months post-surgery, patients were divided into those who remained disease free, and those with subsequent metastases. Vascular parameters for these two groups were compared using t-testing, and receiver operator curve analysis was performed to determine the sensitivity and specificity of these vascular parameters for predicting metastases. Thirty seven (71%) patients underwent curative surgery; data were available for 35: 26 (74%) remained disease free; 9 (26%) recurred (8 metastatic, 1 local). Tumour blood flow differed significantly between disease-free and metastatic patients (76.0 versus 45.7 ml/min/100 g tissue; p = 0.008). With blood flow <64 ml/min/100 g tissue, sensitivity and specificity (95% CI) for development of metastases were 100% (60-100%) and 73% (53-87%), respectively. Our preliminary findings suggest that primary tumour blood flow might potentially be a useful predictor warranting further study.

Objective: The purpose of this study was to determine how the temporal interval between scan acquisitions influences quantitative perfusion CT vascular parameters in colorectal cancer., Subjects and Methods: Forty-five patients with colorectal adenocarcinoma prospectively underwent a 65-second single-anatomic-level perfusion CT study. Blood flow, blood volume, transit time, and permeability-surface area product for a 2-cm tumor coverage were determined with commercial software based on distributed parameter analysis for four temporal intervals (1, 2, 3, and 4 seconds) between acquisitions. Mean vascular values obtained for these intervals were compared by use of analysis of variance with posttesting by the Bonferroni method. Statistical significance was set at 5%., Results: Mean +/- SD blood flow, volume, transit, and permeability-surface area product were 71.5 +/- 34.8 mL/min/100 g tissue, 6.33 +/- 1.96 mL/100 g tissue, 10.8 +/- 5.54 seconds, and 14.9 +/- 3.51 mL/min/100 g tissue, respectively, at 1 second; 86.6 +/- 40.6 mL/min/100 g tissue, 6.30 +/- 2.53 mL/100 g tissue, 10.7 +/- 7.12 seconds, and 14.5 +/- 3.55 mL/min/100 g tissue at 2 seconds; 97.8 +/- 42.7 mL/min/100 g tissue, 5.98 +/- 1.72 mL/100 g tissue, 8.11 +/- 4.37 seconds, and 14.5 +/- 3.58 mL/min/100 g tissue at 3 seconds; and 108.8 +/- 46.0 mL/min/100 g tissue, 6.69 +/- 3.46 mL/100 g tissue, 7.12 +/- 3.54 seconds, and 13.9 +/- 3.49 mL/min/100 g tissue at 4 seconds. Blood flow was overestimated (p = 0.0002) and transit underestimated (p = 0.03) with lengthening acquisition interval. Posttesting revealed that in a comparison with 1-second data, this difference was significant for 3- and 4-second data for blood flow and 4-second data for transit., Conclusion: Increasing the temporal interval from 1 to 4 seconds leads to overestimation of tumor blood flow and underestimation of blood transit in distributed parameter analysis. Use of the helical perfusion CT techniques being developed may lead to inaccurate assessment unless the acquisition interval is shorter than 3 seconds.

Purpose: To establish the relationships between quantitative perfusion computed tomography (CT) parameters-specifically, primary tumor blood flow, blood volume, transit time, and permeability surface-area product-and immunohistologic markers of angiogenesis in colorectal cancer., Materials and Methods: After institutional review board approval and informed patient consent were obtained for this prospective study, 23 patients (11 men, 12 women; mean age, 68.4 years; age range, 34.8-87.1 years) with colorectal adenocarcinoma underwent a 65-second perfusion CT examination, and tumor blood flow, blood volume, mean transit time, and permeability surface-area product were determined. After surgery, resected specimens were sectioned and stained immunohistochemically to identify CD34 for quantification of microvessel density (MVD), to identify smooth muscle actin for assessment of pericyte coverage index, to identify vascular endothelial growth factor (VEGF), and to identify glucose transporter protein (GLUT-1). Perfusion CT measurements were correlated with MVD, pericyte coverage index, VEGF expression, and GLUT-1 expression by using Pearson or Spearman rank correlation analysis, with significance assigned at the 5% level., Results: Mean blood flow, blood volume, transit time, and permeability surface-area product values were 72.1 mL/min/100 g of tissue +/- 28.4 (standard deviation), 6.2 mL/100 g of tissue +/- 1.4, 9.3 seconds +/- 3.9, and 13.9 mL/min/100 g of tissue +/- 3.2, respectively. Blood volume (r = 0.59, P = .002) and permeability surface-area product (r = 0.46, P = .03) correlated positively with MVD, but blood flow (r = 0.27, P = .22) and transit time (r = -0.18, P = .44) did not. There were no significant associations between any perfusion CT parameter and pericyte coverage index (r .05), VEGF score (rho or= .15), or GLUT-1 score (rho < 0.21, P >or= .33)., Conclusion: Tumor permeability surface-area product and blood volume correlate positively with MVD and may reflect the microvascularity of colorectal tumors., ((c) RSNA, 2008.)

Purpose: To prospectively determine whether position and size of tumor region of interest (ROI) influence estimates of colorectal cancer vascular parameters at computed tomography (CT)., Materials and Methods: After institutional review board approval and informed consent, 25 men and 22 women (mean age, 65.8 years) with colorectal adenocarcinoma underwent 65-second CT perfusion study. Blood volume, blood flow, and permeability-surface area product were determined for 40- or 120-mm(2) circular ROIs placed at the tumor edge and center and around (outlining) visible tumor. ROI analysis was repeated by two observers in different subsets of patients to assess intra- and interobserver variation. Measurements were compared by using analysis of variance; a difference with P = .002 was significant., Results: Blood volume, blood flow, and permeability-surface area product measurements were substantially higher at the edge than at the center for both 40- and 120-mm(2) ROIs. For 40-mm(2) ROI, means of the three measurements were 6.9 mL/100 g (standard deviation [SD], 1.4), 108.7 mL/100 g per minute (SD, 39.2), and 16.9 mL/100 g per minute (SD, 4.2), respectively, at the edge versus 5.1 mL/100 g (SD, 1.5), 56.3 mL/100 g per minute (SD, 33.1), and 13.9 mL/100 g per minute (SD, 4.6), respectively, at the center. For 120-mm(2) ROI, means of the three measurements were 6.6 mL/100 g (SD, 1.3), 96.7 mL/100 g per minute (SD, 42.5), and 16.3 mL/100 g per minute (SD, 5.6), respectively, at the edge versus 5.1 mL/100 g (SD, 1.4), 58.3 mL/100 g per minute (SD, 32.5), and 13.4 mL/100 g per minute (SD, 4.3) at the center (P < .0001). Measurements varied substantially depending on the ROI size; values for the ROI for outlined tumor were intermediate between those at the tumor edge and center. Inter- and intraobserver agreement was poor for both 40- and 120-mm(2) ROIs., Conclusion: Position and size of tumor ROI and observer variation substantially influence ultimate perfusion values. ROI for outlined entire tumor is more reliable for perfusion measurements and more appropriate clinically than use of arbitrarily determined smaller ROIs., ((c) RSNA, 2008.)

Angiogenesis is a key factor in the growth and dissemination of colorectal cancer, with significant implications for its clinical management. Previous trials have provided proof-of-principle that inhibition of angiogenesis has the potential to enhance the effectiveness of treatment for this disease. Characterisation of the angiogenic status of the tumour on an individual patient basis could allow for a more targeted approach to treatment. In vivo imaging techniques that assess tumour microvessel function have the potential to improve the management of treatment for patients with colorectal cancer. This review focuses on MRI and CT assessment of colorectal cancer angiogenesis. We discuss the effects that these two techniques have had in the assessment of this disease, including tumour staging and therapeutic assessment. Their comparability with other imaging techniques, in particular ultrasound, and their limitations are also addressed.

Purpose: To prospectively determine the level of agreement between tumor blood volume and permeability measurements obtained with two commercially available perfusion computed tomographic (CT) software packages., Materials and Methods: This study was performed with institutional review board approval; informed consent was obtained from all participants. A total of 44 patients (24 men, 20 women; mean age, 68 years; range, 28-87 years) with proved colorectal cancer were examined prospectively with multi-detector row CT. A 65-second tumor perfusion study was performed after intravenous bolus injection of contrast material. Tumor blood volume and permeability were determined with two methods: adiabatic approximation of distributed parameter analysis and Patlak analysis. Agreement between the results was determined by using Bland-Altman statistics. Within-patient variation was determined by using analysis of variance., Results: The mean values for permeability and blood volume, respectively, were 13.9 mL x 100 mL(-1) x min(-1) +/- 3.7 (standard deviation) and 6.1 mL/100 mL +/- 1.5, as calculated with distributed parameter analysis, and 17.4 mL x 100 mL(-1) x min(-1) +/- 7.3 and 10.1 mL/100 mL +/- 4.2, as calculated with Patlak analysis. The mean difference and 95% limits of agreement, respectively, were -3.6 mL x 100 mL(-1) x min(-1) and -18.4 to 11.2 mL x 100 mL(-1) x min(-1) for permeability and -3.9 mL/100 mL and -10.9 to 3.0 mL/100 mL for blood volume. The coefficient of variation was 37.4% for permeability and 46.5% for blood volume., Conclusion: There was disagreement between the methods used to estimate tumor vascularity, which indicated the measurement techniques were not directly interchangeable., ((c) RSNA, 2007.)

Objective: The purposes of this study were to determine the reproducibility of quantitative colorectal cancer perfusion measurements using dynamic contrast-enhanced MDCT, and to compare this with measurements from skeletal muscle., Subjects and Methods: Ten patients (mean age, 67 years; six men, four women) with histologically proven colorectal cancer were examined prospectively using 4-MDCT. Perfusion studies (cine mode; 4 x 5 mm collimation; 1 acquisition/s; 65 seconds total) were performed through the tumor epicenter after IV bolus contrast administration (iopamidol 340, 100 mL; 5 mL/s) and repeated within 48 hours. Quantitative values for blood volume, blood flow, mean transit time, and permeability were determined using commercial software. Two regions of interest were studied on the axial image: one within the tumor and another within the left gluteal muscle. Measurement reproducibility was assessed using Bland-Altman statistics., Results: For the tumor, the mean difference (95% limits of agreement) was -0.04 mL/100 g tissue (-2.50, 2.42); 8.80 (-50.5, 68.0) mL/100 g tissue/min; -0.99 (-8.19, 6.20) seconds; and 1.20 (-5.42, 7.83) mL/100 g tissue/min for blood volume, blood flow, mean transit time, and permeability, respectively. For muscle, the mean difference (95% limits of agreement) was 0.02 (-1.40, 1.43), 6.60 (-11.2, 24.3), -3.76 (-16.87, 9.35), and 1.30 (-4.68, 7.28), respectively., Conclusion: Quantitative perfusion measurements are reproducible. Measurements from tumor are less variable than from skeletal muscle.

Objective: The objective of our study was to determine inter- and intraobserver agreement of MDCT colorectal cancer perfusion measurements., Subjects and Methods: Thirty-one patients (17 men, 14 women; median age, 69 years) with proven colorectal cancer were examined prospectively using MDCT. A 65-sec dynamic study (cine mode, 4 x 5 mm collimation) was acquired through the tumor after i.v. contrast administration (100 mL of iopamidol 350, 5 mL/sec). Tumor blood volume, blood flow, mean transit time, and permeability measurements were determined by two independent observers using commercial software. Inter- and intraobserver agreement was assessed using the Bland-Altman test., Results: The mean difference for interobserver agreement (95% limits of agreement) was -0.81 mL/100 g tissue (-3.14 to 1.52); -9.94 mL/100 g tissue/min (-51.43 to 32.65); -1.09 sec (-7.05 to 4.86); and -2.90 mL/100 g tissue/min (-11.48 to 5.68) for blood volume, blood flow, mean transit time, and permeability, respectively. The intraclass correlation coefficient was 0.83, 0.89, 0.89, and 0.80, respectively. The mean difference for intraobserver agreement (95% limits of agreement) was 0.12 mL/100 g tissue (-1.90 to 2.14); 0.02 mL/100 g tissue/min (-13.13 to 13.17); -0.19 sec (-3.19 to 2.81); and 0.00 mL/100 g tissue/min (-2.45 to 2.45) for observer 1 and 0.26 mL/100 g tissue (-1.46 to 1.98); 4.47 mL/100 g tissue/min (-26.65 to 35.59); -0.21 sec (-2.48 to 2.06); 1.08 mL/100 g tissue/min (-4.92 to 7.08) for observer 2. The intraclass correlation coefficient was 0.86, 0.98, 0.97, 0.98 for observer 1 and 0.93, 0.96, 0.99, and 0.94, respectively, for observer 2., Conclusion: There is greater inter- than intraobserver agreement for CT vascular perfusion measurements of primary colorectal cancer, which must be addressed for reliable clinical application in therapeutic monitoring.