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Background: Personalising management of primary oesophageal adenocarcinoma requires better risk stratification. Lack of independent validation of proposed imaging biomarkers has hampered clinical translation. We aimed to prospectively validate previously identified prognostic grey-level co-occurrence matrix (GLCM) CT features for 3-year overall survival., Methods: Following ethical approval, clinical and contrast-enhanced CT data were acquired from participants from five institutions. Data from three institutions were used for training and two for testing. Survival classifiers were modelled on prespecified variables ('Clinical' model: age, clinical T-stage, clinical N-stage; 'ClinVol' model: clinical features + CT tumour volume; 'ClinRad' model: ClinVol features + GLCM_Correlation and GLCM_Contrast). To reflect current clinical practice, baseline stage was also modelled as a univariate predictor ('Stage'). Discrimination was assessed by area under the receiver operating curve (AUC) analysis; calibration by Brier scores; and clinical relevance by thresholding risk scores to achieve 90% sensitivity for 3-year mortality., Results: A total of 162 participants were included (144 male; median 67 years [IQR 59, 72]; training, 95 participants; testing, 67 participants). Median survival was 998 days [IQR 486, 1594]. The ClinRad model yielded the greatest test discrimination (AUC, 0.68 [95% CI 0.54, 0.81]) that outperformed Stage (ΔAUC, 0.12 [95% CI 0.01, 0.23]; p = .04). The Clinical and ClinVol models yielded comparable test discrimination (AUC, 0.66 [95% CI 0.51, 0.80] vs. 0.65 [95% CI 0.50, 0.79]; p > .05). Test sensitivity of 90% was achieved by ClinRad and Stage models only., Conclusions: Compared to Stage, multivariable models of prespecified clinical and radiomic variables yielded improved prediction of 3-year overall survival., Clinical Relevance Statement: Previously identified radiomic features are prognostic but may not substantially improve risk stratification on their own., Key Points: • Better risk stratification is needed in primary oesophageal cancer to personalise management. • Previously identified CT features-GLCM_Correlation and GLCM_Contrast-contain incremental prognostic information to age and clinical stage. • Compared to staging, multivariable clinicoradiomic models improve discrimination of 3-year overall survival., (© 2024. The Author(s).)

Computed tomography (CT) is one of the most widespread imaging techniques in clinical use worldwide. CT contrast agents are administered to improve soft tissue contrast and highlight blood vessels. However, the range of CT contrast agents available in the clinic is limited and they suffer from short-circulation times and low k-edge values that result in the need for high doses for in vivo applications. Nanomaterials containing a mixture of electron-dense elements, such as BaYbF 5 nanoparticles, have shown promise as more efficient CT contrast agents, but they require biocompatible coatings for biomedical applications. Here, we explore the use of a bifunctional PEG polymer (5 kDa) containing a terminal bisphosphonate (BP) anchor for efficient binding to the surface of BaYbF 5 nanomaterials. The resulting PEG(5)-BP-BaYbF 5 nanoparticles were synthesized and characterized using TEM, DLS, TGA, XRD and Z-potential measurements. Their in vitro stability was verified and their ability to produce CT contrast in a wide range of X-ray energies, covering preclinical and clinical scanners, was demonstrated. In vitro toxicity studies with PEG(5)-BP-BaYbF 5 in the phagocytic pro-monocytic human cell line U937 did not identify toxic effects, even at high concentrations (30 mM). In vivo, PEG(5)-BP-BaYbF 5 exhibited efficient CT contrast for angiography imaging, highlighting blood vessels and vascular organs, and long circulation times as expected from the PEG coating. However, at late time points (48 h), in vivo toxicity was observed. While the causes could not be completely elucidated, in vitro studies suggest that decomposition and release of Yb 3+ and/or Ba 2+ metal ions after decomposition of PEG(5)-BP-BaYbF 5 may play a role. Overall, despite the promising CT contrast properties, our results suggest that BaYbF 5 nanomaterials may suffer from significant long-term toxicities.

Objective: Non-invasive distinction between squamous cell carcinoma and adenocarcinoma subtypes of non-small-cell lung cancer (NSCLC) may be beneficial to patients unfit for invasive diagnostic procedures or when tissue is insufficient for diagnosis. The purpose of our study was to compare the performance of random forest algorithms utilizing CT radiomics and/or semantic features in classifying NSCLC., Methods: Two thoracic radiologists scored 11 semantic features on CT scans of 106 patients with NSCLC. A set of 115 radiomics features was extracted from the CT scans. Random forest models were developed from semantic (RM-sem), radiomics (RM-rad), and all features combined (RM-all). External validation of models was performed using an independent test data set ( n = 100) of CT scans. Model performance was measured with out-of-bag error and area under curve (AUC), and compared using receiver-operating characteristics curve analysis on the test data set., Results: The median (interquartile-range) error rates of the models were: RF-sem 24.5 % (22.6 - 37.5 %), RF-rad 35.8 % (34.9 - 38.7 %), and RM-all 37.7 % (37.7 - 37.7). On training data, both RF-rad and RF-all gave perfect discrimination (AUC = 1), which was significantly higher than that achieved by RF-sem (AUC = 0.78; p < 0.0001). On test data, however, RM-sem model (AUC = 0.82) out-performed RM-rad and RM-all (AUC = 0.5 and AUC = 0.56; p < 0.0001), neither of which was significantly different from random guess ( p = 0.9 and 0.6 respectively)., Conclusion: Non-invasive classification of NSCLC can be done accurately using random forest classification models based on well-known CT-derived descriptive features. However, radiomics-based classification models performed poorly in this scenario when tested on independent data and should be used with caution, due to their possible lack of generalizability to new data., Advances in Knowledge: Our study describes novel CT-derived random forest models based on radiologist-interpretation of CT scans (semantic features) that can assist NSCLC classification when histopathology is equivocal or when histopathological sampling is not possible. It also shows that random forest models based on semantic features may be more useful than those built from computational radiomic features.

Given the limitations of conventional radiography in the diagnosis of suspected scaphoid fractures on presentation, advanced imaging, particularly magnetic resonance imaging, is a useful additional investigation. We carried out a systematic review of the economic evidence for the use of advanced imaging in the management of suspected scaphoid fractures. Fifteen articles were included in the review. Owing to the heterogeneity of study designs, the type and timing of interventions and the economic analyses performed, direct comparisons between the 15 studies were difficult. From a health care perspective, little could be concluded regarding the economic implications of the use of advanced imaging in clinical practice. However, from a societal perspective, the evidence favours the use of advanced imaging in the management of suspected scaphoid fractures as it does appear to lead to overall cost-savings.

Objectives: To undertake a systematic review to determine the diagnostic performance of whole body MRI (WBMRI) including diffusion weighted sequences (DWI) compared to whole body computed tomography (WBCT) or 18 F-fluorodeoxyglucose positron emission tomography/CT ( 18 F-FDG PET/CT) in patients with myeloma., Methods: Two researchers searched the primary literature independently for WBMRI studies of myeloma. Data were extracted focusing on the diagnostic ability of WBMRI versus WBCT and 18 F-FDG PET/CT. Meta-analysis was intended., Results: 6 of 2857 articles were eligible that included 147 patients, published from 2008 to 2016. Studies were heterogeneous including both newly diagnosed & relapsed patients. All were single centre studies. Four of the six studies (66.7%) accrued prospectively and 5/6 (83.3%, 3 prospective) included WBMRI and 18 F-FDG PET/CT. Three of seven (42.9%) included DWI. The lack of an independent reference standard for individual lesions was noted in 5/6 (83.3%) studies. Studies reported that WBMRI detected more lesions than 18 F-FDG PET/CT (sensitivity 68-100% versus 47-100%) but was less specific (specificity 37-83% versus 62-85.7%). No paper assessed impact on management., Conclusions: Studies were heterogeneous, the majority lacking an independent reference standard. Future prospective trials should address these limitations and assess the impact of WBMRI on management., (Copyright © 2018. Published by Elsevier B.V.)

Perfusion CT was first described in the 1970s but has become accepted as a clinical technique in recent years. In oncological practice Perfusion CT allows the downstream effects of therapies on the tumour vasculature to be monitored. From the dynamic changes in tumour and vascular enhancement following intravenous iodinated contrast agent administration, qualitative and quantitative parameters may be derived that reflect tumour perfusion, blood volume, and microcirculatory changes with treatment. This review outlines the mechanisms of action of available therapies and state-of-the-art imaging practice., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Purpose: We aimed to assess computed tomography (CT) intratumoral heterogeneity changes, and compared the prognostic ability of the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, an alternate response method (Crabb), and CT heterogeneity in non-small cell lung cancer treated with chemotherapy with and without bevacizumab., Materials and Methods: Forty patients treated with chemotherapy (group C) or chemotherapy and bevacizumab (group BC) underwent contrast-enhanced CT at baseline and after 1, 3, and 6 cycles of chemotherapy. Radiologic response was assessed using RECIST 1.1 and an alternate method. CT heterogeneity analysis generating global and locoregional parameters depicting tumor image spatial intensity characteristics was performed. Heterogeneity parameters between the 2 groups were compared using the Mann-Whitney U test. Associations between heterogeneity parameters and radiologic response with overall survival were assessed using Cox regression., Results: Global and locoregional heterogeneity parameters changed with treatment, with increased tumor heterogeneity in group BC. Entropy [group C: median -0.2% (interquartile range -2.2, 1.7) vs. group BC: 0.7% (-0.7, 3.5), P=0.10] and busyness [-27.7% (-62.2, -5.0) vs. -11.5% (-29.1, 92.4), P=0.10] showed a greater reduction in group C, whereas uniformity [1.9% (-8.0, 9.8) vs. -5.0% (-13.9, 5.6), P=0.10] showed a relative increase after 1 cycle but did not reach statistical significance. Two (9%) and 1 (6%) additional responders were identified using the alternate method compared with RECIST in group C and group BC, respectively. Heterogeneity parameters were not significant prognostic factors., Conclusions: The alternate response method described by Crabb identified more responders compared with RECIST. However, both criteria and baseline imaging heterogeneity parameters were not prognostic of survival.

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: Malignant pleural mesothelioma (MPM) is a disease with poor prognosis despite multimodal therapy but there is variation in survival between patients. Prognostic information is therefore potentially valuable in managing patients, particularly in the context of clinical trials where patients could be stratified according to risk. Therefore we have evaluated the prognostic ability of parameters derived from baseline 2-[(18)F]fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography ((18)F-FDG PET/CT)., Methods: In order to determine the relationships between metabolic activity and prognosis we reviewed all (18)F-FDG PET/CT scans used for pretreatment staging of MPM patients in our institution between January 2005 and December 2011 (n = 60) and measured standardised uptake values (SUV) including mean, maximum and peak values, metabolic tumour volume (MTV) and total lesion glycolysis (TLG). Overall survival (OS) or time to last censor was recorded, as well as histological subtypes., Results: Median follow-up was 12.7 months (1.9-60.9) and median OS was 14.1 months (1.9-54.9). By univariable analysis histological subtype (p = 0.013), TLG (p = 0.024) and MTV (p = 0.038) were significantly associated with OS and SUVmax was borderline (p = 0.051). On multivariable analysis histological subtype and TLG were associated with OS but at borderline statistical significance (p = 0.060 and 0.058, respectively). No statistically significant differences in any PET parameters were found between the epithelioid and non-epithelioid histological subtypes., Conclusion: (18)F-FDG PET/CT parameters that take into account functional volume (MTV, TLG) show significant associations with survival in patients with MPM before adjusting for histological subtype and are worthy of further evaluation to determine their ability to stratify patients in clinical trials.

Purpose: To determine the association between tumor heterogeneity, morphologic tumor response, and overall survival in primary esophageal cancer treated with chemotherapy and radiation therapy (CRT)., Materials and Methods: After an institutional review board waiver was obtained, contrast material-enhanced computed tomographic (CT) studies in 36 patients with stage T2 or greater esophageal tumors who underwent contrast-enhanced CT before and after CRT between 2005 and 2008 were analyzed in terms of whole-tumor texture, with quantification of entropy, uniformity, mean gray-level intensity, kurtosis, standard deviation of the histogram, and skewness for fine to coarse textures (filters 1.0-2.5, respectively). The association between texture parameters and survival time was assessed by using Kaplan-Meier analysis and a Cox proportional hazards model. Survival models involving texture parameters and combinations of texture and morphologic response assessment were compared with morphologic assessment alone by means of receiver operating characteristic (ROC) analysis., Results: Posttreatment medium entropy of less than 7.356 (median overall survival, 33.2 vs 11.7 months; P = .0002), coarse entropy of less than 7.116 (median overall survival, 33.2 vs 11.7 months; P = .0002), and medium uniformity of 0.007 or greater (median overall survival, 33.2 vs 11.7 months; P = .0002) were associated with improved survival time. These remained significant prognostic factors after adjustment for stage and age: entropy (filter 2.0: hazard ratio [HR] = 5.038, P = .0004; filter 2.5: HR = 5.038, P = .0004) and uniformity (HR = 0.199, P = .0004). Survival models that included a combination of pretreatment entropy and uniformity with maximal wall thickness assessment, respectively, performed better than morphologic assessment alone (area under the ROC curve, 0.767 vs 0.487 [P = .00005] and 0.802 vs 0.487 [P = .0003])., Conclusion: Posttreatment texture parameters are associated with survival time, and the combination of pretreatment texture parameters and maximal wall thickness performed better in survival models than morphologic tumor response alone., (© RSNA, 2013.)

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)

Anatomical-based imaging is used widely for the evaluation of diffuse and focal liver, including detection, characterization, and therapy response assessment. However, a limitation of anatomical-based imaging is that structural changes may occur relatively late in a disease process. By applying conventional anatomical-imaging methods in a more functional manner, specific pathophysiologic alterations of the liver may be assessed and quantified. There has been an increasing interest in both the clinical and research settings, with the expectation that functional-imaging techniques may help solve common diagnostic dilemmas that conventional imaging alone cannot. This review considers the most common functional magnetic resonance imaging, computed tomography, and ultrasound imaging techniques that may be applied to the liver., (Copyright © 2013 Elsevier Inc. All rights reserved.)

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 correlate computed tomographic (CT) texture in non-small cell lung cancer (NSCLC) with histopathologic markers for angiogenesis and hypoxia., Materials and Methods: The study was institutional review board approved, and informed consent was obtained. Fourteen patients with NSCLC underwent CT prior to intravenous administration of pimonidazole (0.5 g/m(2)), a marker of hypoxia, 24 hours before surgery. Texture was assessed for unenhanced and contrast material-enhanced CT images by using a software algorithm that selectively filters and extracts texture at different anatomic scales (1.0 [fine detail] to 2.5 [coarse features]), with quantification of the standard deviation (SD) of all pixel values and the mean value of positive pixels (MPP) and uniformity of distribution of positive gray-level pixel values (UPP). After surgery, matched tumor sections were stained for angiogenesis (CD34 expression) and for markers of hypoxia (glucose transporter protein 1 [Glut-1] and pimonidazole). The percentage and average intensity of the tumor stained were assessed. A linear mixed-effects model was used to assess the correlations between CT texture and staining intensity., Results: SD and MPP quantified from medium to coarse texture on contrast-enhanced CT images showed significant associations with the average intensity of tumor staining with pimonidazole (for SD: filter value, 2.5; slope = 0.003; P = .0003). UPP (medium to coarse texture) on unenhanced CT images showed a significant inverse association with tumor Glut-1 expression (filter value, 2.5; slope = -115.13; P = .0008). MPP quantified from medium to coarse texture on both unenhanced and contrast-enhanced CT images showed significant inverse associations with tumor CD34 expression (unenhanced CT: filter value, 1.8; slope = -0.0008; P = .003; contrast-enhanced CT: filter value, 1.8; slope = -0.0006; P = .004)., Conclusion: Texture parameters derived from CT images of NSCLC have the potential to act as imaging correlates for tumor hypoxia and angiogenesis., Supplemental Material: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.12112428/-/DC1., (RSNA, 2012)

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: 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.

(18)F-Fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) is now routinely used in oncological imaging for diagnosis and staging and increasingly to determine early response to treatment, often employing semiquantitative measures of lesion activity such as the standardized uptake value (SUV). However, the ability to predict the behaviour of a tumour in terms of future therapy response or prognosis using SUVs from a baseline scan prior to treatment is limited. It is recognized that medical images contain more useful information than may be perceived with the naked eye, leading to the field of "radiomics" whereby additional features can be extracted by computational postprocessing techniques. In recent years, evidence has slowly accumulated showing that parameters obtained by texture analysis of radiological images, reflecting the underlying spatial variation and heterogeneity of voxel intensities within a tumour, may yield additional predictive and prognostic information. It is hoped that measurement of these textural features may allow better tissue characterization as well as better stratification of treatment in clinical trials, or individualization of future cancer treatment in the clinic, than is possible with current imaging biomarkers. In this review we focus on the literature describing the emerging methods of texture analysis in (18)FDG PET/CT, as well as other imaging modalities, and how the measurement of spatial variation of voxel grey-scale intensity within an image may provide additional predictive and prognostic information, and postulate the underlying biological mechanisms.

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.

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.

The aim was to determine the feasibility of vascular quantification of the bowel wall for different anatomical segments of the colorectum. Following institutional ethical approval and informed consent, 39 patients with colorectal cancer underwent perfusion CT. Blood flow (BF), blood volume (BV), mean transit time (MTT), and permeability surface area product (PS) were assessed for different segments of the colorectum: ascending, transverse, descending colon, sigmoid, or rectum, that were distant from the tumor, and which were proven normal on contemporary colonoscopy, and subsequent imaging and clinical follow up. Mean (SD) for BF, BV, MTT and PS for the different anatomical colorectal segments were obtained and compared using a pooled t-test. Significance was at 5%. Assessment was not possible in 9 of 39 (23%) patients as the bowel wall was ≤ 5 mm precluding quantitative analysis. Forty-four segments were evaluated in the remaining 30 patients. Mean BF was higher in the proximal than distal colon: 24.0 versus 17.8 mL/min/100g tissue; p=0.009; BV, MTT and PS were not significantly different; BV: 3.46 versus 3.15 mL/100g tissue, p=0.45; MTT: 15.1 versus 18.3s; p=0.10; PS: 6.84 versus 8.97 mL/min/100 tissue, p=0.13, respectively. In conclusion, assessment of bowel wall perfusion may fail in 23% of patients. The colorectum demonstrates segmental differences in perfusion., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

With the emergence of novel targeted therapies, imaging techniques that assess tumor vascular support have gained credence for response assessment alongside standard response criteria. Computed tomography (CT) perfusion techniques that quantify regional tumor blood flow, blood volume, flow-extraction product, and permeability-surface area product through standard kinetic models are attractive, but the level of evidence for CT perfusion to be a truly mature biomarker remains insufficient. Studies to date have not been powered to assess this. Future studies that include good quality prospective validation correlating perfusion CT to outcome end points in the trial setting are needed to take CT perfusion forward as a biomarker in oncology.

Unlabelled: Inflammation and angiogenesis are hypothesized to be important factors contributing to plaque vulnerability, whereas calcification is suggested to confer stability. To investigate this in vivo, we combined CT angiography and PET and compared the findings with immunohistochemistry for patients undergoing carotid endarterectomy., Methods: Twenty-one consecutive patients (18 men, 3 women; mean age ± SD, 68.3 ± 7.3) undergoing carotid endarterectomy were recruited for combined carotid (18)F-FDG PET/CT angiography. Plaque (18)F-FDG uptake was quantified with maximum standardized uptake value, and CT angiography quantified percentage plaque composition (calcium and lipid). Surgical specimens underwent ex vivo CT aiding image registration, followed by immunohistochemical staining for CD68 (macrophage density) and vascular endothelial growth factor (angiogenesis). Relationships between imaging and immunohistochemistry were assessed with Spearman rank correlation and multivariable regression., Results: The mean (±SD) surgically excised carotid plaque (18)F-FDG metabolism was 2.4 (±0.5) versus 2.2 (±0.3) contralaterally (P = 0.027). There were positive correlations between plaque (18)F-FDG metabolism and immunohistochemistry with CD68 (ρ = 0.55; P = 0.011) and vascular endothelial growth factor (ρ = 0.47; P = 0.031). There was an inverse relationship between plaque (18)F-FDG metabolism and plaque percentage calcium composition on CT (ρ = -0.51; P = 0.018) and between calcium composition and immunohistochemistry with CD68 (ρ = -0.57; P = 0.007). Regression showed that maximum standardized uptake value and calcium composition were independently significant predictors of angiogenesis, and calcium composition was a predictor of macrophage density., Conclusion: We provide in vivo evidence that increased plaque metabolism is associated with increased biomarkers of angiogenesis and inflammation, whereas plaque calcification is inversely related to PET and histologic biomarkers of inflammation.

Purpose: To assess changes in tumor computed tomographic (CT) texture after two cycles of treatment with tyrosine kinase inhibitors (TKIs) and to determine if tumor texture correlates with measured time to progression in patients with metastatic renal cell cancer who received TKIs., Materials and Methods: A waiver of institutional review board approval was obtained for this retrospective analysis. Contrast material-enhanced CT texture parameters were assessed in 39 patients with metastatic renal cell cancer who received a TKI. A total of 87 metastases were analyzed at baseline and after two treatment cycles. Changes in tumor entropy and uniformity were derived with a software algorithm that selectively filters and extracts texture at different scales (fine to coarse detail: 1.0-2.5) and were recorded. Response assessment was also obtained by using response evaluation criteria in solid tumors (RECIST), as well as Choi and modified Choi criteria. The correlation of texture parameters and standard criteria with measured time to progression was assessed by using Kaplan-Meier analysis and a Cox regression model. Statistical significance was set at 5%., Results: Tumor entropy decreased by 3%-45% and uniformity increased by 5%-21% for the different scale values after administration of a TKI. With a threshold change of -2% or less for uniformity at a coarse scale value of 2.5, Kaplan-Meier curves of the proportion of patients without disease progression were significantly different and better than those for standard response assessment (P = .008 vs P = .267, P = .053, and P = .042 for RECIST, Choi, and modified Choi criteria, respectively). Cox regression analysis showed that texture uniformity was an independent predictor of time to progression (odds ratio, 4.02; 95% confidence interval: 1.52, 10.65; P = .005)., Conclusion: CT texture analysis reflecting tumor heterogeneity is an independent factor associated with time to progression and has potential as a predictive imaging biomarker of response of metastatic renal cancer to targeted therapy., (© RSNA, 2011.)

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.

Manipulation of tumor vasculature has emerged as a promising therapeutic strategy in advanced non-small cell lung cancer (NSCLC). Bevacizumab has been licensed for first-line therapy in combination with standard chemotherapy in advanced NSCLC, whereas inhibitors of platelet-derived growth factor receptors and other tyrosine kinases are currently in clinical trials for the treatment of advanced NSCLC. Perfusion computed tomography is a promising biomarker in NSCLC. As a measure of tumor perfusion and angiogenesis, perfusion computed tomography may provide invaluable pharmacodynamic information in early-phase clinical trials, monitor the vascular effects of antiangiogenic or vascular-targeting drug treatment, and provide prognostic and predictive information. Current volumetric techniques, affording a coverage of up to 28 cm, permit clinically relevant, high-quality, whole tumor evaluation.

Background: Response assessment is critical in evaluating effectiveness of anticancer treatment. Tyrosine kinase inhibitors (TKIs) in renal cell carcinoma (RCC) are associated with significant clinical benefit but may not result in significant tumor size reduction. Thus standard size-based response assessment with RECIST is insensitive, resulting in low response rates which do not reflect disease control measured by time to progression. We compared the use of combined size and density response criteria with standard size based criteria in metastatic RCC patients treated with TKI's., Results: Partial response (PR) and stable disease (SD) defined by modified criteria successfully identified patients with a long TTP (448 days) or short TTP (89 days) respectively (p = 0.002). Neither RECIST nor standard Choi criteria successfully discriminated between patients having a short or long clinical benefit., Patients and Methods: CT scans from 32 patients with metastatic RCC treated with either sunitinib (18) or cediranib (14) were assessed. Twelve patients were excluded from the analysis as ten had non-contrast enhanced scans due to renal impairment and two stopped treatment due to toxicity. Scans from 20 evaluable patients at baseline and 12 w on treatment were assessed using RECIST, Choi and modified criteria in which both a 10% decrease in size and 15% decrease in density were required to define a partial response (PR). Response assessment performed using each of the three methods was compared with time to disease progression (TTP) defined by RECIST using Kaplan-Meier statistics and Log-rank test with significance at 5%., Conclusion: A combined reduction in both size and arterial phase density of RCC metastases treated with TKIs correlates with TTP. RECIST and standard Choi criteria appear inferior.

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.

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.)

The aim of this study is to quantify myocardial perfusion during coronary CT angiography using data from a modified timing test-bolus acquisition. Institutional review board approval and informed consent were obtained. Nineteen patients with suspected coronary artery disease underwent combined coronary CT angiography and cardiac (82)Rubidium-PET perfusion. Prior to the CT angiogram a retrospectively ECG-gated dynamic test bolus was obtained following 25 mls of IV contrast medium injected at 5 ml/s. Images were acquired every 1.5 s for 30 s using 4 x 1.25-mm slices at 120 kV, 35 mAs. Regions of interest were drawn to delineate the myocardium and aorta on the resulting transaxial images. Time density curves were created and perfusion calculated using two simple approaches: maximum-slope method and peak method. In patients with normal PET myocardial perfusion, the mean (SD) resting myocardial perfusion estimated by CT using the maximum-slope method was 0.89 (+/-0.27) ml/min/g and 0.93 (+/-0.21) ml/min/g at end-systole and end-diastole, respectively, and 0.69 (+/-0.11) ml/min/g and 0.79 (+/-0.19) at end-systole and end-diastole, respectively, for the peak method. Thus quantification of myocardial perfusion from a routine coronary CT angiography test bolus is possible. CT-derived myocardial perfusion values are consistent with published values derived from other techniques.

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 determine whether computed tomographic (CT) perfusion measurements in prospectively recruited patients can be used to differentiate between diverticulitis and colorectal cancer and to compare this discrimination with that of standard morphologic criteria., Materials and Methods: After institutional review board approval and written informed consent were obtained, 60 patients (24 men, 36 women; mean age, 69 years; range, 33.5-90.4 years; 20 patients with cancer, 20 with diverticulitis, and 20 with inactive diverticular disease) underwent CT perfusion imaging at the level of the colonic abnormality, and perfusion parameters were calculated. Analysis of variance was used to investigate any differences in perfusion between the patient groups. Two independent observers also analyzed an abdominopelvic CT study obtained immediately after the CT perfusion study and noted standard morphologic criteria for differential diagnosis. The sensitivity and specificity of CT perfusion measurements for determining the diagnostic category were compared with morphologic criteria by means of multivariate analysis to identify the most discriminatory criteria., Results: Mean blood volume, blood flow, transit time, and permeability were significantly different between patients with cancer and those with diverticulitis (P < .0001); patients with cancer had the highest blood volume, blood flow, and permeability and the shortest transit time. The most discriminatory criteria for determining diagnostic category were blood volume, transit time, permeability, and presence of pericolonic nodes (P = .05, .02, .04, and .02, respectively). Blood volume and blood flow each had a sensitivity of 80% and had specificity of 70% and 75%, respectively, for cancer in comparison with standard morphologic criteria: less than 5 cm of bowel involvement (45% sensitivity, 95% specificity), presence of a mass (85% sensitivity, 90% specificity), pericolonic inflammation (75% sensitivity, 5% specificity), and pericolonic nodes (90% sensitivity, 45% specificity)., Conclusion: CT perfusion measurements enable differentiation and better discrimination, in comparison with morphologic criteria, between cancer and diverticulitis., ((c) RSNA, 2007.)

Purpose: To prospectively determine if gammaH2AX (phosphorylated form of H2AX histone variant)-based visualization and quantification of DNA damage induced in peripheral blood mononuclear cells (PBMCs) can be used to estimate the radiation dose received by adult patients who undergo multidetector computed tomography (CT)., Materials and Methods: After institutional review board approval and written informed patient consent were obtained, eight women and five men (mean age, 63.8 years) who would be undergoing chest-abdominal-pelvic CT or chest CT only were recruited. Venous blood samples obtained before scanning were exposed to different radiation doses in vitro and incubated for 5-30 minutes to obtain reference values of gammaH2AX focus yield. Additional blood samples were taken 5-30 minutes after CT. Leukocytes were isolated, fixed, and stained for gammaH2AX expression. The gammaH2AX focus yields were determined with fluorescence microscopy, and the radiation doses delivered during CT were estimated by comparing post-CT focus yields with in vitro pre-CT focus yields. These CT radiation doses were compared with doses calculated by using phantom dosimetry and Monte Carlo data sets. Data were analyzed by using linear regression, the dispersion index test, and the contaminated Poisson method., Results: Compared with the gammaH2AX focus yields in blood samples taken before CT (0.06 focus per cell+/-0.01 [mean+/-standard error of mean]), the yields in blood samples taken 5 minutes after chest-abdominal-pelvic CT (0.52 focus per cell+/-0.02) were 8-10-fold higher and corresponded to a mean radiation dose of 16.4 mGy (95% confidence interval: 15.1, 17.7). The mean yield of 0.24 focus per cell+/-0.04 in one patient after chest CT corresponded to a mean radiation dose of 6.3 mGy+/-1.4. In comparison, phantom dosimetry-calculated total blood doses were 13.85 mGy with whole-body CT and 5.16 mGy with chest CT., Conclusion: gammaH2AX focus yield in blood cells may be a useful quantitative biomarker of human low-level radiation exposure., (Copyright (c) RSNA, 2007.)

Objective: To date, quantitative assessment of tumor vascularity using perfusion CT has been limited to a single tumor level, with the potential for measurement error in heterogeneous tumors. We aimed to determine if greater z-axis tumor coverage improves the reproducibility of perfusion CT measurements in lung cancer., Subjects and Methods: Paired perfusion studies were performed on 10 patients who had histologically confirmed advanced non-small cell lung cancer. Using 16-MDCT, multiple sequential volumetric acquisitions encompassing the entire tumor were acquired after infusion of i.v. contrast material. Using Patlak analysis, median values of tumor permeability (mL/100 mL/min) and blood volume (mL/100 mL) were measured for 10-mm z-axis coverage, and for 40-mm z-axis coverage in each of the paired perfusion studies. Measurement reproducibility was evaluated using Bland-Altman statistics., Results: Mean difference (95% limits of agreement) for tumor permeability was 1.4 (-4.0 to 6.8) for 10-mm coverage and 0.8 (-3.6 to 5.2) for 40-mm coverage. Mean difference (95% limits of agreement) for blood volume was 1.9 (-5.1 to 8.9) for 10-mm coverage and 1.4 (-3.7 to 6.6) for 40-mm coverage. The coefficient of variation for permeability was 18.7% for 10-mm coverage, improving to 11.9% for 40-mm coverage. The coefficient of variation for blood volume was 41.7% for 10-mm coverage, improving to 32.6% for 40-mm coverage., Conclusion: Our results show that an improvement in tumor perfusion measurement reproducibility may be achieved with greater z-axis coverage.

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.

Institutional review board approval and informed consent were obtained for this study. The aim of the study was to prospectively assess, in patients with lung cancer, the reproducibility of a quantitative whole tumor perfusion computed tomographic (CT) technique. Paired CT studies were performed in 10 patients (eight men, two women; mean age, 66 years) with lung cancer. Whole tumor permeability and blood volume were measured, and reproducibility was evaluated by using Bland-Altman statistics. Coefficient of variation of 9.49% for permeability and 26.31% for blood volume and inter- and intraobserver variability ranging between 3.30% and 6.34% indicate reliable assessment with this whole tumor technique., ((c) RSNA, 2006.)

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.

Purpose: To investigate the effects of hyoscine butylbromide and an inflatable rectal balloon catheter on luminal distention during computed tomographic (CT) colonography., Materials and Methods: One hundred thirty-six subjects undergoing CT colonography were randomized to receive either 20 mg or 40 mg of hyoscine butylbromide or no spasmolytic. Subjects were also independently randomized to undergo CT colonography with an inflatable rectal balloon catheter or a standard thin rectal tube. Multi-detector row CT colonography was performed with patients in prone and supine positions, with colonic segmental distention assessed by a single observer with a four-point scale. A simple assessment of whether distention was adequate for clinical interpretation was also made, and the effect of hyoscine butylbromide and catheter use was examined by using multivariate ordered logistic regression., Results: Administration of hyoscine butylbromide was associated with significantly improved cecal (P =.05), ascending (P =.001), and transverse (P <.001) colonic distention when patients were supine and improved ascending (P <.001) and descending (P <.001) colonic distention when patients were prone. Compared with control subjects, patients given a spasmolytic had odds of 6.49 for clinically adequate distention throughout all colonic segments (P =.001). There was no incremental advantage with use of a 40-mg dose. In contrast, rectal balloon catheter use was not significantly associated with improved distention., Conclusion: Hyoscine butylbromide improves colonic distention during CT colonography and should be routinely administered where it is available. Use of a thin rectal tube for insufflation is adequate., (Copyright RSNA, 2003)