Comparative accuracy and cost-effectiveness of dynamic contrast-enhanced CT and positron emission tomography in the characterisation of solitary pulmonary nodules.

INTRODUCTION: Dynamic contrast-enhanced CT (DCE-CT) and positron emission tomography/CT (PET/CT) have a high reported accuracy for the diagnosis of malignancy in solitary pulmonary nodules (SPNs). The aim of this study was to compare the accuracy and cost-effectiveness of these. METHODS: In this prospective multicentre trial, 380 participants with an SPN (8-30 mm) and no recent history of malignancy underwent DCE-CT and PET/CT. All patients underwent either biopsy with histological diagnosis or completed CT follow-up. Primary outcome measures were sensitivity, specificity and overall diagnostic accuracy for PET/CT and DCE-CT. Costs and cost-effectiveness were estimated from a healthcare provider perspective using a decision-model. RESULTS: 312 participants (47% female, 68.1±9.0 years) completed the study, with 61% rate of malignancy at 2 years. The sensitivity, specificity, positive predictive value and negative predictive values for DCE-CT were 95.3% (95% CI 91.3 to 97.5), 29.8% (95% CI 22.3 to 38.4), 68.2% (95% CI 62.4% to 73.5%) and 80.0% (95% CI 66.2 to 89.1), respectively, and for PET/CT were 79.1% (95% CI 72.7 to 84.2), 81.8% (95% CI 74.0 to 87.7), 87.3% (95% CI 81.5 to 91.5) and 71.2% (95% CI 63.2 to 78.1). The area under the receiver operator characteristic curve (AUROC) for DCE-CT and PET/CT was 0.62 (95% CI 0.58 to 0.67) and 0.80 (95% CI 0.76 to 0.85), respectively (p<0.001). Combined results significantly increased diagnostic accuracy over PET/CT alone (AUROC=0.90 (95% CI 0.86 to 0.93), p<0.001). DCE-CT was preferred when the willingness to pay per incremental cost per correctly treated malignancy was below £9000. Above £15 500 a combined approach was preferred. CONCLUSIONS: PET/CT has a superior diagnostic accuracy to DCE-CT for the diagnosis of SPNs. Combining both techniques improves the diagnostic accuracy over either test alone and could be cost-effective. TRIAL REGISTRATION NUMBER: NCT02013063.

Combined (99m)Tc-methoxyisobutylisonitrile scintigraphy and fine-needle aspiration cytology offers an accurate and potentially cost-effective investigative strategy for the assessment of solitary or dominant thyroid nodules.

PURPOSE: Fine-needle aspiration (FNA) has revolutionised the care of patients with thyroid nodules and is the initial investigation of choice. However, as a result of nondiagnostic (Thy1) and nonneoplastic (Thy2) specimens, it remains an imperfect sole solution with a range of sensitivities and a high inadequate ratio. Therefore the British Thyroid Association (BTA) guidelines recommend a second FNA immediately for Thy1 specimens and 3-6 months later for Thy2 specimens. Patients must be followed up to exclude malignancy. In this study we assessed the performance of MIBI scintigraphy for diagnosing thyroid malignancy and the cost-effectiveness of a combined FNA/MIBI investigative strategy for the management of thyroid nodules. METHODS: The diagnostic performance of MIBI scintigraphy was calculated from a retrospective review of local data combined with a meta-analysis of the published literature. Decision tree analysis was used to calculate the cost-effectiveness of a combined FNA/MIBI investigative strategy compared to the BTA guidelines. RESULTS: From 712 patients, the sensitivity, specificity, PPV and NPV of MIBI scintigraphy for the diagnosis of malignancy were 96 %, 46 %, 34 % and 97 %, respectively. MIBI-based strategies were more accurate and associated with lower cost per patient (£1,855/2,125 vs. £2,445/2,801) and lower cost per cancer diagnosed (£1,902/2,179 vs. £2,469/2,828) with negligible change in life expectancy. CONCLUSION: Due to its high NPV, MIBI scintigraphy can usefully exclude malignancy for Thy1 and Thy2 lesions. Its low specificity means MIBI scintigraphy cannot be recommended as a first-line investigation, but as a second-line investigation MIBI scintigraphy may lead to a lower rate of unnecessary thyroidectomies. Combined FNA/MIBI strategies are potentially cost-effective in the management of solitary or dominant thyroid nodules.

Assessment of primary colorectal cancer heterogeneity by using whole-tumor texture analysis: contrast-enhanced CT texture as a biomarker of 5-year survival.

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.

Non-small cell lung cancer: histopathologic correlates for texture parameters at CT.

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.

Diagnostic performance of prospective same-day 18F-FDG PET/MRI and 18F-FDG PET/CT in the staging and response assessment of lymphoma.

BACKGROUND: Accurate staging and response assessment are essential for prognosis and to guide treatment in patients with lymphoma. The aim of this study was to compare the diagnostic performance of FDG PET/MRI versus FDG PET/CT in adult patients with newly diagnosed Hodgkin and Non- Hodgkin lymphoma. METHODS: In this single centre study, 50 patients were prospectively recruited. FDG PET/MRI was performed after staging FDG PET/CT using a single injection of 18F-FDG. Patients were invited to complete same-day FDG PET/MRI with FDG PET/CT at interim and end of treatment response assessments. Performance was assessed using PET/CT as the reference standard for disease site identification, staging, response assessment with Deauville score and concordance in metabolic activity. RESULTS: Staging assessment showed perfect agreement (κ = 1.0, P = 0) between PET/MRI and PET/CT using Ann Arbor staging. There was excellent intermodality correlation with disease site identification at staging (κ = 0.976, P < 0.001) with FDG PET/MRI sensitivity of 96% (95% CI, 94-98%) and specificity of 100% (95% CI, 99-100%). There was good correlation of disease site identification at interim assessment (κ = 0.819, P < 0.001) and excellent correlation at end-of-treatment assessment (κ = 1.0, P < 0.001). Intermodality agreement for Deauville scores was good at interim assessment (κ = 0.808, P < 0.001) and excellent at end-of-treatment assessment (κ = 1.0, P = 0). There was good-excellent concordance in SUV max and mean between modalities across timepoints. Minimum calculated radiation patient effective dose saving was 54% between the two modalities per scan. CONCLUSION: With high concordance in disease site identification, staging and response assessment, PET/MR is a potentially viable alternative to PET/CT in lymphoma that minimises radiation exposure.

Integrated 18F-fluorodeoxyglucose-positron emission tomography/dynamic contrast-enhanced computed tomography to phenotype non-small cell lung carcinoma.

We applied modern molecular and functional imaging to the pretreatment assessment of lung cancer using combined dynamic contrast-enhanced computed tomography (DCE-CT) and (18)F-fluorodeoxyglucose-positron emission tomography ((18)F-FDG-PET) to phenotype tumors. Seventy-four lung cancer patients were prospectively recruited for (18)F-FDG-PET/DCE-CT using PET/64-detector CT. After technical failures, there were 64 patients (35 males, 29 females; mean age [± SD] 67.5 ± 7.9 years). DCE-CT yielded tumor peak enhancement (PE) and standardized perfusion value (SPV). The uptake of (18)F-FDG quantified on PET as the standardized uptake value (SUV(max)) assessed tumor metabolism. The median values for SUV(max) and SPV were used to define four vascular-metabolic phenotypes. There were associations (Spearman rank correlation [rs]) between tumor size and vascular-metabolic parameters: SUV(max) versus size (rs  =  .40, p  =  .001) and SUV/PE versus size (r  =  .43, p < .001). Patients with earlier-stage (I-IIA, n  =  30) disease had mean (± SD) SUV/PE 0.36 ± 0.28 versus 0.56 ± 0.32 in later-stage (stage IIB-IV, n  =  34) disease (p  =  .007). The low metabolism with high vascularity phenotype was significantly more common among adenocarcinomas (p  =  .018), whereas the high metabolism with high vascularity phenotype was more common among squamous cell carcinomas (p  =  .024). Other non-small cell lung carcinoma tumor types demonstrated a high prevalence of the high metabolism with low vascularity phenotype (p  =  .028). We show that tumor subtypes have different vascular-metabolic associations, which can be helpful clinically in managing lung cancer patients to hone targeted therapy.

Dynamic contrast-enhanced CT compared with positron emission tomography CT to characterise solitary pulmonary nodules: the SPUtNIk diagnostic accuracy study and economic modelling.

BACKGROUND: Current pathways recommend positron emission tomography-computerised tomography for the characterisation of solitary pulmonary nodules. Dynamic contrast-enhanced computerised tomography may be a more cost-effective approach. OBJECTIVES: To determine the diagnostic performances of dynamic contrast-enhanced computerised tomography and positron emission tomography-computerised tomography in the NHS for solitary pulmonary nodules. Systematic reviews and a health economic evaluation contributed to the decision-analytic modelling to assess the likely costs and health outcomes resulting from incorporation of dynamic contrast-enhanced computerised tomography into management strategies. DESIGN: Multicentre comparative accuracy trial. SETTING: Secondary or tertiary outpatient settings at 16 hospitals in the UK. PARTICIPANTS: Participants with solitary pulmonary nodules of ≥ 8 mm and of ≤ 30 mm in size with no malignancy in the previous 2 years were included. INTERVENTIONS: Baseline positron emission tomography-computerised tomography and dynamic contrast-enhanced computer tomography with 2 years' follow-up. MAIN OUTCOME MEASURES: Primary outcome measures were sensitivity, specificity and diagnostic accuracy for positron emission tomography-computerised tomography and dynamic contrast-enhanced computerised tomography. Incremental cost-effectiveness ratios compared management strategies that used dynamic contrast-enhanced computerised tomography with management strategies that did not use dynamic contrast-enhanced computerised tomography. RESULTS: A total of 380 patients were recruited (median age 69 years). Of 312 patients with matched dynamic contrast-enhanced computer tomography and positron emission tomography-computerised tomography examinations, 191 (61%) were cancer patients. The sensitivity, specificity and diagnostic accuracy for positron emission tomography-computerised tomography and dynamic contrast-enhanced computer tomography were 72.8% (95% confidence interval 66.1% to 78.6%), 81.8% (95% confidence interval 74.0% to 87.7%), 76.3% (95% confidence interval 71.3% to 80.7%) and 95.3% (95% confidence interval 91.3% to 97.5%), 29.8% (95% confidence interval 22.3% to 38.4%) and 69.9% (95% confidence interval 64.6% to 74.7%), respectively. Exploratory modelling showed that maximum standardised uptake values had the best diagnostic accuracy, with an area under the curve of 0.87, which increased to 0.90 if combined with dynamic contrast-enhanced computerised tomography peak enhancement. The economic analysis showed that, over 24 months, dynamic contrast-enhanced computerised tomography was less costly (£3305, 95% confidence interval £2952 to £3746) than positron emission tomography-computerised tomography (£4013, 95% confidence interval £3673 to £4498) or a strategy combining the two tests (£4058, 95% confidence interval £3702 to £4547). Positron emission tomography-computerised tomography led to more patients with malignant nodules being correctly managed, 0.44 on average (95% confidence interval 0.39 to 0.49), compared with 0.40 (95% confidence interval 0.35 to 0.45); using both tests further increased this (0.47, 95% confidence interval 0.42 to 0.51). LIMITATIONS: The high prevalence of malignancy in nodules observed in this trial, compared with that observed in nodules identified within screening programmes, limits the generalisation of the current results to nodules identified by screening. CONCLUSIONS: Findings from this research indicate that positron emission tomography-computerised tomography is more accurate than dynamic contrast-enhanced computerised tomography for the characterisation of solitary pulmonary nodules. A combination of maximum standardised uptake value and peak enhancement had the highest accuracy with a small increase in costs. Findings from this research also indicate that a combined positron emission tomography-dynamic contrast-enhanced computerised tomography approach with a slightly higher willingness to pay to avoid missing small cancers or to avoid a 'watch and wait' policy may be an approach to consider. FUTURE WORK: Integration of the dynamic contrast-enhanced component into the positron emission tomography-computerised tomography examination and the feasibility of dynamic contrast-enhanced computerised tomography at lung screening for the characterisation of solitary pulmonary nodules should be explored, together with a lower radiation dose protocol. STUDY REGISTRATION: This study is registered as PROSPERO CRD42018112215 and CRD42019124299, and the trial is registered as ISRCTN30784948 and ClinicalTrials.gov NCT02013063. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 17. See the NIHR Journals Library website for further project information.

A nodule found on a lung scan can cause concern as it may be a sign of cancer. Finding lung cancer nodules when they are small (i.e. < 3 cm) is very important. Most nodules are not cancerous. Computerised tomography (cross-sectional images created from multiple X-rays) and positron emission tomography­computerised tomography (a technique that uses a radioactive tracer combined with computerised tomography) are used to see whether or not a nodule is cancerous; although they perform well, improvements are required. This study compared dynamic contrast-enhanced computerised tomography with positron emission tomography­computerised tomography scans to find out which test is best. Dynamic contrast-enhanced computerised tomography involves injection of a special dye into the bloodstream, followed by repeated scans of the nodule over several minutes. We assessed the costs to the NHS of undertaking the different scans, relative to their benefits, to judge which option was the best value for money. We recruited 380 patients from 16 hospitals across England and Scotland, of whom 312 had both dynamic contrast-enhanced computerised tomography and positron emission tomography­computerised tomography scans. We found that current positron emission tomography­computerised tomography is more accurate, providing a correct diagnosis in 76% of cases, than the new dynamic contrast-enhanced computerised tomography, which provides a correct diagnosis in 70% of cases. Although dynamic contrast-enhanced computerised tomography cannot replace positron emission tomography­computerised tomography, it may represent good-value use of NHS resources, especially if it is performed before positron emission tomography­computerised tomography and they are used in combination. Although more research is required, it may be possible in the future to perform dynamic contrast-enhanced computerised tomography at the same time as positron emission tomography­computerised tomography in patients with suspected lung cancer or if a lung nodule is found on a lung screening programme at the time of the computerised tomography examination. This may reduce the need for some people to have positron emission tomography­computerised tomography.

Assessment of response to tyrosine kinase inhibitors in metastatic renal cell cancer: CT texture as a predictive biomarker.

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.

¹8F-FDG PET and biomarkers for tumour angiogenesis in early breast cancer.

PURPOSE: Tumour angiogenesis is an independent and strong prognostic factor in early breast carcinoma. We performed this study to investigate the ability of (18)F-FDG to detect angiogenesis in early breast carcinoma using PET/CT. METHODS: Twenty consecutive patients with early (T1-T2) breast carcinoma were recruited prospectively for 18F-FDG PET/CT. The PET/CT data were used to calculate whole tumour maximum standardized uptake value (SUV(max)) and mean standardized uptake value (SUV(mean)). All patients underwent subsequent surgery without prior chemotherapy or radiotherapy. The excised tumour underwent immunohistochemistry for vascular endothelial growth factor (VEGF), CD105 and glucose transporter protein 1 (GLUT1). RESULTS: The SUV(max) showed the following correlation with tumour histology: CD105: r = 0.60, p = 0.005; GLUT1: r = 0.21, p = 0.373; VEGF: r = -0.16, p = 0.496. The SUV(mean) showed the following correlation with tumour histology: CD105: r = 0.65, p = 0.002; GLUT1: r = 0.34, p = 0.144; VEGF: r = -0.18, p = 0.443 CONCLUSION: (18)F-FDG uptake is highly significantly associated with angiogenesis as measured by the immunohistochemistry with CD105 for new vessel formation. Given that tumour angiogenesis is an important prognostic indicator and a predictor of treatment response, (18)F-FDG PET may have a role in the management of primary breast cancer patients even in early-stage disease.

Multiparametric imaging of tumor response to therapy.

There is an increasing opportunity to perform multifunctional imaging at a variety of organ sites with relatively short examination times. Each technique yields quantitative parameters that reflect specific aspects of the underlying tumor or tissue biology. Many biomarkers have emerged that provide unique information on tumor behavior, including response to treatment. The multiparametric approach combines the information from different functional imaging techniques; this goes beyond what can be achieved by using any single functional technique, thus allowing an improved understanding of biologic processes and of responses to therapeutic interventions. Multiparametric imaging has many potential clinical roles; it is useful for pharmaceutical drug development and for predicting therapeutic efficacy.

Three-dimensional textural analysis of brain images reveals distributed grey-matter abnormalities in schizophrenia.

OBJECTIVES: Three-dimensional (3-D) selective- and relative-scale texture analysis (TA) was applied to structural magnetic resonance (MR) brain images to quantify the presence of grey-matter (GM) and white-matter (WM) textural abnormalities associated with schizophrenia. MATERIALS AND METHODS: Brain TA comprised volume filtration using the Laplacian of Gaussian filter to highlight fine, medium and coarse textures within GM and WM, followed by texture quantification. Relative TA (e.g. ratio of fine to medium) was also computed. T1-weighted MR whole-brain images from 32 participants with diagnosis of schizophrenia (n = 10) and healthy controls (n = 22) were examined. Five patients possessed marker alleles (SZ8) associated with schizophrenia on chromosome 8 in the pericentriolar material 1 gene while the remaining five had not inherited any of the alleles (SZ0). RESULTS: Filtered fine GM texture (mean grey-level intensity; MGI) most significantly differentiated schizophrenic patients from controls (P = 0.0058; area under the receiver-operating characteristic curve = 0.809, sensitivity = 90%, specificity = 70%). WM measurements did not distinguish the two groups. Filtered GM and WM textures (MGI) correlated with total GM and WM volume respectively. Medium-to-coarse GM entropy distinguished SZ0 from controls (P = 0.0069) while measures from SZ8 were intermediate between the two. CONCLUSIONS: 3-D TA of brain MR enables detection of subtle distributed morphological features associated with schizophrenia, determined partly by susceptibility genes.

Discrepancies between positron emission tomography/magnetic resonance imaging and positron emission tomography/computed tomography in a cohort of oncological patients.

INTRODUCTION: This study aims to evaluate discrepant findings between positron emission tomography/magnetic resonance imaging (PET/MRI) and positron emission tomography/computed tomography (PET/CT) in a cohort of oncological patients and to undertake a phantom study to assess the potential for extended PET acquisitions to lead to false-positive findings on PET/MRI. METHODS: Discrepant findings from a series of 106 patients undergoing same-day 18 F-fluorodeoxyglucose (FDG)-PET/CT and PET/MRI were reviewed. Phantom studies explored the potential for PET acquisition time to contribute to discrepancy. RESULTS: There were 14 discrepant cases, 5 (35.7%) of which related to PET/MRI acquisitions that had been extended to 10 min. Three of these five cases proved to be falsely positive. Phantom studies showed greater contrast recovery and signal to noise ratio for 10-min PET/MRI acquisitions compared to 2-min acquisitions using PET/CT. There were no discrepancies when PET/CT showed disseminated disease (P = 0.036). CONCLUSIONS: Extended PET/MRI acquisitions used to accommodate multiple MRI sequences may be associated with false-positive findings compared to PET/CT. PET/MRI is more likely to have incremental value when the prior probability for disseminated disease is low.

Colorectal cancer: texture analysis of portal phase hepatic CT images as a potential marker of survival.

PURPOSE: To assess the utility of texture analysis of liver computed tomographic (CT) images by determining the effect of acquisition parameters on texture and by comparing the abilities of texture analysis and hepatic perfusion CT to help predict survival for patients with colorectal cancer. MATERIALS AND METHODS: The study comprised a phantom test and a clinical evaluation of 48 patients with colorectal cancer who had consented to retrospective analysis of hepatic perfusion CT data acquired during a research study approved by the institutional review board. Both components involved texture analysis to quantify the relative contribution of CT features between 2 and 12 pixels wide to overall image brightness and uniformity. The effect of acquisition factors on texture was assessed on CT images of a cylindric phantom filled with water obtained by using tube currents between 100 and 250 mAs and voltages between 80 and 140 kVp. Texture on apparently normal portal phase CT images of the liver and hepatic perfusion parameters were related to patient survival by using Kaplan-Meier survival analysis. RESULTS: A texture parameter that compared the uniformity of distribution of CT image features 10 and 12 pixels wide exhibited the least variability with CT acquisition parameters (maximum coefficient of variation, 2.6%) and was the best predictor of patient survival (P < .005). There was no significant association between survival and hepatic perfusion parameters. CONCLUSION: The study provides preliminary evidence that analysis of liver texture on portal phase CT images is potentially a superior predictor of survival for patients with colorectal cancer than CT perfusion imaging. SUPPLEMENTAL MATERIAL: http://radiology.rsnajnls.org/cgi/content/full/2502071879/DC1.

Cost-effectiveness of 99mTc-sestamibi in predicting response to chemotherapy in patients with lung cancer: systematic review and meta-analysis.

UNLABELLED: Multidrug resistance (MDR) is a major problem in lung cancer. (99m)Tc-methoxyisobutylisonitrile ((99m)Tc-MIBI) has been demonstrated to be a noninvasive marker for the diagnosis of MDR-related P glycoprotein and MDR-associated protein expression in various solid tumors. Studies have shown that (99m)Tc-MIBI could play a significant role in the management of lung cancer; for example, it could be used in the selection of patients for chemotherapy or radiotherapy or in combined protocols before the start of treatment. Accurate selection of chemosensitive patients with (99m)Tc-MIBI would result not only in effective treatment of patients but also in significant cost savings for health care providers. There is increasing pressure on health care providers to consider costs in medical decision making, particularly in the last decade, as several economic evaluations have appeared in the medical literature. The aims of this study were to undertake a systematic review of the performance of (99m)Tc-MIBI imaging in the assessment of treatment resistance in lung cancer and to use the findings of the review in a decision tree analysis of the potential cost-effectiveness of (99m)Tc-MIBI imaging in selecting lung cancer patients for chemotherapy. METHODS: This study included a systematic review of the literature and a meta-analysis together with a cost-effectiveness analysis of studies with a decision tree analysis model. RESULTS: Analysis of the studies revealed that the overall sensitivity of (99m)Tc-MIBI in identifying responders to chemotherapy was 94%, the specificity was 90%, and the accuracy was 92%. The sensitivity analysis revealed an incremental cost-effectiveness ratio of greater than pound30,000 ( approximately $42,900) for the strategy of treating all patients to recover the small loss of life expectancy (7.5 d) associated with the use of (99m)Tc-MIBI to preselect patients for chemotherapy. CONCLUSION: (99m)Tc-MIBI SPECT can accurately predict which patients with lung cancer will respond to chemotherapy. The use of (99m)Tc-MIBI to preselect patients for chemotherapy has the potential to yield significant cost savings in the health care system without a significant loss of life expectancy for patients.

Metabolic-flow relationships in primary breast cancer: feasibility of combined PET/dynamic contrast-enhanced CT.

PURPOSE: To assess the feasibility and first experience of combined (18)F-FDG-PET)/dynamic contrast-enhanced (DCE) CT in evaluating breast cancer. METHODS: Nine consecutive female patients (mean age 64.2 years, range 52-74 years) with primary breast carcinoma were prospectively recruited for combined (18)F-FDG PET/DCE-CT. Dynamic CT data were used to calculate a range of parameters of tumour vascularity, and tumour (18)F-FDG uptake (standardized uptake value, SUVmax) was used as a metabolic indicator. RESULTS: One tumour did not enhance and was excluded. The mean tumour SUVmax was 7.7 (range 2.4-26.1). The mean values for tumour perfusion, perfusion normalized to cardiac output, standard perfusion value (SPV) and permeability were 41 ml/min per 100 g (19-59 ml/min per 100 g), 0.56%/100 g (0.33-1.09%/100 g), 3.6 (2.5-5.9) and 0.15/min (0.09-0.30/min), respectively. Linear regression analysis showed a positive correlation between tumour SUV and tumour perfusion normalized to cardiac output (r=0.55, p=0.045) and a marginal correlation between tumour SUV and tumour SPV (r=0.19, p=0.065). There were no significant correlations between tumour SUV and tumour perfusion (r=0.29, p=0.401) or permeability (r=0.03, p=0.682). CONCLUSION: The first data from combined (18)F-FDG-PET/DCE-CT in breast cancer are reported. The technique was successful in eight of nine patients. Breast tumour metabolic and vascular parameters were consistent with previous data from (15)O-H(2)O-PET.

Combination bone marrow imaging using positron emission tomography (PET)-MRI in plasma cell dyscrasias: correlation with prognostic laboratory values and clinicopathological diagnosis.

OBJECTIVE: This prospective observational study of positron emission tomography (PET)-MRI findings in 16 consecutive newly diagnosed patients with a plasma cell dyscrasia describes and compares MRI-detected myeloma lesions with 18F-fludeoxyglucose PET-avid myeloma lesions, and correlates quantitative imaging findings to a range of biochemical and prognostic parameters. METHODS: Simultaneously acquired whole body PET and MRI images were evaluated qualitatively for the presence of focal or generalised abnormalities of bone marrow (BM) on either modality. Quantitative analysis comprised mean standardised uptake values (SUVmean) and fractional water content of the BM measured from PET and chemical shift MRI images of the second to fourth lumbar vertebrae. RESULTS: Final diagnoses comprised symptomatic myeloma (n = 10), asymptomatic myeloma (n = 4) and monoclonal gammopathy of uncertain significance (n = 2). 8/10 patients with symptomatic myeloma demonstrated BM abnormalities on qualitative assessment of MRI compared to 4/10 on PET. BM SUVmean inversely correlated with serum albumin (r = 0.57, p = 0.017). BM water fraction correlated with trephine cellularity and blood platelet count (r = 0.78, p = 0.00039 and r = 0.61, p = 0.0013 respectively). BM water fraction correlated with SUVmean in patients with low plasma cell burden (r = 0.91, p = 0.0015) but not in patients with high plasma cell burden (r = 0.18, p = 0.61). CONCLUSION: PET-MRI shows promise in both morphological and functional multiparametric quantitative assessment of myeloma. ADVANCES IN KNOWLEDGE: For the first time, multiparametric imaging in myeloma has been shown to predict BM abnormalities and correlate with known biochemical prognostic markers, moving PET-MRI beyond simple diagnostic applications into potential prognostic and treatment selection applications.

Three-dimensional selective-scale texture analysis of computed tomography pulmonary angiograms.

OBJECTIVES: This feasibility study aims to develop 3-dimensional (3D) selective-scale texture analysis of computed tomography pulmonary angiography to identify texture correlates for ventilated and vascular lung for visual and quantitative assessment of pulmonary disorders with altered vasculature. MATERIALS AND METHODS: Computed tomography pulmonary angiography examinations of 8 patients were considered in this study; 3 had normal lungs, 3 had pulmonary embolism (PE1, PE2, and PE3), 1 had only emphysema (PEmp), whereas the final patient had both emphysema and embolism (PEE). Before texture analysis, an initial automated segmentation procedure to include only the lung parenchyma and generation of isometric volume were carried out. From this segmented volume, ventilated lung and pulmonary vessels were separately selected. Texture analysis comprised 2 stages: 1) volume filtration using 3D Laplacian of Gaussian filter to highlight fine and coarse textures within ventilated and vascular lung, followed by 2) quantification of texture using mean gray-level intensity, entropy and uniformity both globally and at 3 anatomic sections of the lung, ie, anterior, middle, and posterior. Quantification of texture was also performed on the unfiltered computed tomography lung dataset. Volume rendering and image fusion of ventilated and vascular lung texture were employed for visualization. RESULTS: For fine texture quantified as mean gray-level intensity in ventilated lung, a postural gradient compatible with known pulmonary physiology was demonstrated and texture was different in emphysematous lung (PEmp and PEE) when compared with nonemphysematous lung (normals, PE1, PE2, and PE3) consistent with altered ventilation. Coarse texture in vascular lung demonstrated a descending trend in entropy (or ascending trend in uniformity) for normals, followed by embolism only (PE1, PE2, and PE3) and finally for emphysematous lung (PEmp and PEE) suggesting a correlation with degree of vascularity (or perfusion). 3D images of ventilated and vascular lung texture highlighted mismatched and matched defects in patients with pulmonary disorders. CONCLUSIONS: This feasibility study demonstrated that 3D filtered texture analysis can potentially provide correlates for ventilated and vascular lung, which may be useful in the diagnosis of PE in the presence of other causes of altered vascularity.

Additional Clinical Value for PET/MRI in Oncology: Moving Beyond Simple Diagnosis.

Initial clinical research comparing the diagnostic performance of PET/MRI and PET/CT has largely shown equivalent diagnostic capabilities for these modalities in oncology. These uncertainties about the magnitude of diagnostic benefit are compounded by the considerable health economic challenges associated with clinical implementation. Therefore, there is a need to identify ways to extend the use of this technology beyond simple diagnosis so that PET/MRI can add sufficient clinical value beyond PET/CT or MRI alone and become a cost-effective imaging modality in clinical practice. A major advantage of PET/MRI over other imaging modalities is the ability to generate multiple quantitative images from a single examination. This article describes how a multiparametric PET/MRI approach not only can add clinical value through contributing to precision medicine but also can establish PET/MRI as a potentially cost-effective imaging modality in oncology.

Hepatic enhancement in colorectal cancer: texture analysis correlates with hepatic hemodynamics and patient survival.

RATIONALE AND OBJECTIVES: Perfusion imaging of the liver has attracted interest as a potential means for earlier detection of hepatic metastases, but the techniques are complex and do not form part of routine imaging protocols. This study assesses whether the hemodynamic status of the liver of patients with colorectal cancer but apparently normal hepatic morphology is reflected by texture features within a single portal-phase contrast enhanced computed tomography (CT) image and correlates texture with overall survival. MATERIALS AND METHODS: Portal-phase CT images from 27 patients with colorectal cancer but no apparent hepatic metastases were processed using a band-pass filter that highlighted image features at different spatial frequencies. A range of parameters reflecting liver texture on filtered images were correlated against CT hepatic perfusion index (HPI) and patient survival. RESULTS: After image filtration, entropy values from hepatic regions were inversely correlated with HPI (r=-0.503978, P=.007355), and directly correlated with survival (r=0.489642, P=.009533). An entropy value below 2.0 identified four patients who died within 36 months of their CT scan with sensitivity 100% and specificity 65% (P<.03). CONCLUSION: The hemodynamic status of the liver is reflected by subtle changes in coarse texture on portal phase images that can be revealed by texture analysis. Texture analysis has the potential to identify colorectal cancer patients with an apparently normal portal phase hepatic CT but reduced survival.

In search of biologic correlates for liver texture on portal-phase CT.

RATIONALE AND OBJECTIVES: The acceptance of computer-assisted diagnosis (CAD) in clinical practice has been constrained by the scarcity of identifiable biologic correlates for CAD-based image parameters. This study aims to identify biologic correlates for computed tomography (CT) liver texture in a series of patients with colorectal cancer. MATERIALS AND METHODS: In 28 patients with colorectal cancer, total hepatic perfusion (THP), hepatic arterial perfusion, and hepatic portal perfusion (HPP) were measured using perfusion CT. Hepatic glucose use was also determined from positron emission tomography (PET) and expressed as standardized uptake value (SUV). A hepatic phosphorylation fraction index (HPFI) was determined from both SUV and THP. These physiologic parameters were correlated with CAD parameters namely hepatic densitometry, selective-scale, and relative-scale texture features in apparently normal areas of portal-phase hepatic CT. RESULTS: For patients without liver metastases, a relative-scale texture parameter correlated inversely with SUV (r = -0.587, P = .007) and, positively with THP (r = 0.512, P = .021) and HPP (r = 0.451, P = .046). However, this relative texture parameter correlated most significantly with HPFI (r = -0.590, P = .006). For patients with liver metastases, although not significant an opposite trend was observed between these physiologic parameters and relative texture features (THP: r < -0.4, HPFI: r > 0.35). CONCLUSION: Total hepatic blood flow and glucose metabolism are two distinct but related biologic correlates for liver texture on portal phase CT, providing a rationale for the use of hepatic texture analysis as a indicator for patients with colorectal cancer.