Dynamic contrast-enhanced computed tomography for the diagnosis of solitary pulmonary nodules: a systematic review and meta-analysis.

INTRODUCTION: A systematic review and meta-analysis were performed to determine the diagnostic performance of dynamic contrast-enhanced computed tomography (DCE-CT) for the differentiation between malignant and benign pulmonary nodules. METHODS: Ovid MEDLINE and EMBASE were searched for studies published up to October 2018 on the diagnostic accuracy of DCE-CT for the characterisation of pulmonary nodules. For the index test, studies with a minimum of a pre- and post-contrast computed tomography scan were evaluated. Studies with a reference standard of biopsy for malignancy, and biopsy or 2-year follow-up for benign disease were included. Study bias was assessed using QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies). The sensitivities, specificities, and diagnostic odds ratios were determined along with 95% confidence intervals (CIs) using a bivariate random effects model. RESULTS: Twenty-three studies were included, including 2397 study participants with 2514 nodules of which 55.3% were malignant (1389/2514). The pooled accuracy results were sensitivity 94.8% (95% CI 91.5; 96.9), specificity 75.5% (69.4; 80.6), and diagnostic odds ratio 56.6 (24.2-88.9). QUADAS 2 assessment showed intermediate/high risk of bias in a large proportion of the studies (52-78% across the domains). No difference was present in sensitivity or specificity between subgroups when studies were split based on CT technique, sample size, nodule size, or publication date. CONCLUSION: DCE-CT has a high diagnostic accuracy for the diagnosis of pulmonary nodules although study quality was indeterminate in a large number of cases. KEY POINTS: • The pooled accuracy results were sensitivity 95.1% and specificity 73.8% although individual studies showed wide ranges of values. • This is comparable to the results of previous meta-analyses of PET/CT (positron emission tomography/computed tomography) diagnostic accuracy for the diagnosis of solitary pulmonary nodules. • Robust direct comparative accuracy and cost-effectiveness studies are warranted to determine the optimal use of DCE-CT and PET/CT in the diagnosis of SPNs.

MRI texture analysis (MRTA) of T2-weighted images in Crohn's disease may provide information on histological and MRI disease activity in patients undergoing ileal resection.

OBJECTIVES: To associate MRI textural analysis (MRTA) with MRI and histological Crohn's disease (CD) activity. METHODS: Sixteen patients (mean age 39.5 years, 9 male) undergoing MR enterography before ileal resection were retrospectively analysed. Thirty-six small (≤3 mm) ROIs were placed on T2-weighted images and location-matched histological acute inflammatory scores (AIS) measured. MRI activity (mural thickness, T2 signal, T1 enhancement) (CDA) was scored in large ROIs. MRTA features (mean, standard deviation, mean of positive pixels (MPP), entropy, kurtosis, skewness) were extracted using a filtration histogram technique. Spatial scale filtration (SSF) ranged from 2 to 5 mm. Regression (linear/logistic) tested associations between MRTA and AIS (small ROIs), and CDA/constituent parameters (large ROIs). RESULTS: Skewness (SSF = 2 mm) was associated with AIS [regression coefficient (rc) 4.27, p = 0.02]. Of 120 large ROI analyses (for each MRI, MRTA feature and SSF), 15 were significant. Entropy (SSF = 2, 3 mm) and kurtosis (SSF = 3 mm) were associated with CDA (rc 0.9, 1.0, -0.45, p = 0.006-0.01). Entropy and mean (SSF = 2-4 mm) were associated with T2 signal [odds ratio (OR) 2.32-3.16, p = 0.02-0.004], [OR 1.22-1.28, p = 0.03-0.04]. MPP (SSF = 2 mm) was associated with mural thickness (OR 0.91, p = 0.04). Kurtosis (SSF = 3 mm), standard deviation (SSF = 5 mm) were associated with decreased T1 enhancement (OR 0.59, 0.42, p = 0.004, 0.007). CONCLUSIONS: MRTA features may be associated with CD activity. KEY POINTS: • MR texture analysis features may be associated with Crohn's disease histological activity. • Texture analysis features may correlate with MR-dependent Crohn's disease activity scores. • The utility of MR texture analysis in Crohn's disease merits further investigation.

Central autonomic network mediates cardiovascular responses to acute inflammation: relevance to increased cardiovascular risk in depression?

Inflammation is a risk factor for both depression and cardiovascular disease. Depressed mood is also a cardiovascular risk factor. To date, research into mechanisms through which inflammation impacts cardiovascular health rarely takes into account central effects on autonomic cardiovascular control, instead emphasizing direct effects of peripheral inflammatory responses on endothelial reactivity and myocardial function. However, brain responses to inflammation engage neural systems for motivational and homeostatic control and are expressed through depressed mood state and changes in autonomic cardiovascular regulation. Here we combined an inflammatory challenge, known to evoke an acute reduction in mood, with neuroimaging to identify the functional brain substrates underlying potentially detrimental changes in autonomic cardiovascular control. We first demonstrated that alterations in the balance of low to high frequency (LF/HF) changes in heart rate variability (a measure of baroreflex sensitivity) could account for some of the inflammation-evoked changes in diastolic blood pressure, indicating a central (rather than solely local endothelial) origin. Accompanying alterations in regional brain metabolism (measured using (18)FDG-PET) were analysed to localise central mechanisms of inflammation-induced changes in cardiovascular state: three discrete regions previously implicated in stressor-evoked blood pressure reactivity, the dorsal anterior and posterior cingulate and pons, strongly mediated the relationship between inflammation and blood pressure. Moreover, activity changes within each region predicted the inflammation-induced shift in LF/HF balance. These data are consistent with a centrally-driven component originating within brain areas supporting stressor evoked blood pressure reactivity. Together our findings highlight mechanisms binding psychological and physiological well-being and their perturbation by peripheral inflammation.

Measurements of heterogeneity in gliomas on computed tomography relationship to tumour grade.

To undertake a preliminary study that uses CT texture analysis (CTTA) to quantify heterogeneity in gliomas on contrast-enhanced CT and to assess the relationship between tumour heterogeneity and grade. Retrospective analysis of contrast enhanced CT images was performed in 44 patients with histologically proven cerebral glioma between 2007 and 2010. 11 tumours were low grade (Grade I = 3; Grade II, = 8) and 33 high grade (Grade III = 10, Grade IV = 23). CTTA assessment of tumour heterogeneity was performed using a proprietary software algorithm (TexRAD) that selectively filters and extracts textures at different anatomical scales between filter values 1.0 (fine detail) and 2.5 (coarse features). Heterogeneity was quantified as standard deviation (SD) with or without filtration. Tumour heterogeneity, size and attenuation were correlated with tumour grade. For each parameter, receiver operating characteristics characterised the diagnostic performance for discrimination of high grade from low grade glioma and of grade III tumours from grade IV. Further the CTTA was compared to the radiological diagnosis. Tumour heterogeneity correlated significantly with grade (SD without filtration rs = 0.664, p < 0.001, SD with coarse filtration (rs = 0.714, p < 0.001). Tumour size and attenuation showed only moderate correlations with tumour grade (rs = 0.426, p = 0.004 and rs = 0.447, p = 0.002 respectively). Coarse texture was the best discriminator between high and low grade tumours (AUC 0.832, p < 0.0001) and between grade III and grade IV gliomas (AUC = 0.878 p = 0.0001). Compared to the radiological diagnosis, CTTA further characterised the indetermined cases. By quantifying tumour heterogeneity, CTTA has the potential to provide a marker of tumour grade for patients with cerebral glioma. By differentiating between high and low grade tumours, CTTA could possibly assist clinical management.

Tumour heterogeneity in non-small cell lung carcinoma assessed by CT texture analysis: a potential marker of survival.

PURPOSE: To establish the potential for tumour heterogeneity in non-small cell lung cancer (NSCLC) as assessed by CT texture analysis (CTTA) to provide an independent marker of survival for patients with NSCLC. MATERIALS AND METHODS: Tumour heterogeneity was assessed by CTTA of unenhanced images of primary pulmonary lesions from 54 patients undergoing (18)F-fluorodeoxyglucose (FDG) PET-CT for staging of NSCLC. CTTA comprised image filtration to extract fine, medium and coarse features with quantification of the distribution of pixel values (uniformity) within the filtered images. Receiver operating characteristics identified thresholds for PET and CTTA parameters that were related to patient survival using Kaplan-Meier analysis. RESULTS: The median (range) survival was 29.5 (1-38) months. 24, 10, 14 and 6 patients had tumour stages I, II, III and IV respectively. PET stage and tumour heterogeneity assessed by CTTA were significant independent predictors of survival (PET stage: Odds ratio 3.85, 95% confidence limits 0.9-8.09, P = 0.002; CTTA: Odds ratio 56.4, 95% confidence limits 4.79-666, p = 0.001). SUV was not a significantly associated with survival. CONCLUSION: Assessment of tumour heterogeneity by CTTA of non-contrast enhanced images has the potential for to provide a novel, independent predictor of survival for patients with NSCLC. KEY POINTS: Computed tomography is a routine staging procedure in non-small cell lung cancer. CT texture analysis (CTTA) can quantify heterogeneity within these lung tumours. CTTA seems to offer a novel independent predictor of survival for NSCLC. CTTA could contribute to disease risk-stratification for patients with NSCLC.

Economic analysis of the use of coronary calcium scoring as an alternative to stress ECG in the non-invasive diagnosis of coronary artery disease.

OBJECTIVE: To conduct an economic analysis (EA) of coronary calcium scoring (CCS) using a 0 score, as alternative to stress electrocardiography (sECG) in diagnosing coronary artery disease (CAD). METHOD: A decision tree was constructed to compare four strategies for investigation of suspected CAD previously assessed in the formulation of clinical guidelines for the United Kingdom (UK) to two new strategies incorporating CCS. Sensitivity (96%; 95% CI 95.4-96.4%) and specificity (40%; 95% CI 38.7-41.4%) values for CCS were derived from a meta-analysis of 10,760 patients. Other input variables were obtained from a previous EA and average prices for hospital procedures in the UK. A threshold of £30,000/Quality-adjusted Life Year (QALY) was considered cost-effective. RESULTS: Using net monetary benefit calculations, CCS-based strategies were found to be cost-effective compared to sECG equivalents at all assessed prevalence of CAD. Using CCS prior to myocardial perfusion scintigraphy (MPS) and catheter angiography (CA) was found to be cost-effective at pre-test probabilities (PTP) below 30%. CONCLUSIONS: Adoption of CCS as an alternative to sECG in investigating suspected stable angina in low PTP population (<30%) would be cost-effective. In patients with PTP of CAD >30%, proceeding to MPS or CA would be more cost-effective than performing either CCS or sECG. KEY POINTS: Coronary calcium scoring (CCS) is useful for assessing coronary artery atherosclerosis It can be performed with multi-detector CT, which is now widely available It plays a role in excluding disease in suspected stable angina Our study assesses its role in this setting as alternative to stress-ECG Adoption of CCS as an alternative to sECG could prove cost-effective.

Utilization of dynamic CT perfusion in the study of intracranial meningiomas and their surrounding tissue.

OBJECTIVE: To use CT perfusion (CTP) to assess levels of ischemia in brain areas around intracranial meningiomas. MATERIALS AND METHODS: Fifteen patients with intracranial meningiomas were analysed preoperatively with CTP study. The cerebral blood flow (CBF), cerebral blood volume (CBV) and time to peak (TTP) were measured in the edema, peritumoral edema and in the normal areas of brain. RESULTS: The peritumoral edema measured a mean CBF of 17.36 ml/min/100 ml (median=15.8) and the mean CBF value in the whole edema was 93.86 ml/min/100 ml (median=79.9). The mean CBV measured in the peritumoral edema was 2.7 (median=2.3) and the measured mean CBV of edema was 15 (median=13.2). In the region of the peritumoral edema, the mean CBF and CBV were lower than in the edema bed. Normal brain remote from the edema measured less CBF (mean=28.36 ml/min/100 ml, median=29.7) and CBV (mean=4.1, median=3.8) than the edema. Six patients were noted to have CBF of less than 15 ml/min/100 ml in the perilesional edema. The measured mean CBF and CBV in the normal area of brain were higher than in the peritumoral edema, while the TTP was greater in the perilesional edema (mean=11, median=10.4) when compared with areas of normal brain (mean=9.9, median=9.5) with statistically significant p values. CONCLUSION: The values obtained elucidate the fact that perilesional edematous areas are ischemic. By subset analysis, it may be possible to identify those areas with recoverable tissue from non-recoverable tissue.

Simultaneous positron emission tomography and magnetic resonance imaging for the detection and characterisation of liver lesions in patients with colorectal cancer: A pictorial review.

Patients with colorectal cancer undergo frequent diagnostic imaging to stage the extent of metastatic disease and assess response to treatment. Imaging is typically via diagnostic contrast-enhanced CT or combined FDG-PET/CT. However, recent research has demonstrated promising benefits of combined FDG-PET/MRI in oncologic imaging due to the superior soft-tissue contrast of MRI. The extent of both intrahepatic and extrahepatic disease is important in establishing treatment options for colorectal cancer patients, and FDG-PET/CT and dedicated liver imaging are often both required. FDG-PET/MRI offers the advantage of a single examination which can be completed within a similar duration as dedicated liver MRI imaging. This improves patient convenience and anatomical co-registration between PET and MRI imaging and provides a potential cost benefit. The diagnostic benefits of FDG-PET/MRI include the simultaneous characterisation of focal liver lesions, exclusion of extrahepatic disease, the detection of additional hepatic metastases and extrahepatic disease, and the multi-parametric assessment of treatment response. This pictorial review highlights examples of these benefits.

The cost-effective use of 18F-FDG PET in the presurgical evaluation of medically refractory focal epilepsy.

UNLABELLED: This study applied decision tree analysis to evaluate the sensitivity, specificity, and cost-effectiveness of clinical algorithms that incorporate 18F-FDG PET. METHODS: A cohort of 176 patients was studied. The localization rate, accuracy, therapeutic impact on the presurgical decision-making process, and correlation with the postsurgical outcome were assessed for the tests commonly performed for seizure localization. Decision tree sensitivity analysis compared 3 imaging strategies with a baseline strategy of medical therapy for all: video-electroencephalography monitoring (VEM)/MRI strategy, in which patients underwent VEM and brain MRI only, and +SPECT and +PET strategies, in which patients with an indeterminate VEM/MRI result underwent ictal SPECT or interictal 18F-FDG PET, respectively. RESULTS: The localization rates for VEM, MRI, 18F-FDG PET, ictal SPECT, and intracranial electroencephalography (EEG) were 62.2%, 35.8%, 75.0%, 60.0%, and 93.8%. The VEM/MRI strategy had the lowest cost per class I/II outcome, but the additional costs per class I/II outcome for the +PET and +SPECT strategies were always below the minimum reported cost savings for a class I/II outcome. There were no valid conditions in which the +SPECT strategy had a lower cost per class I/II outcome than the +PET strategy. Within the range of cost savings estimated to be associated with a class I/II outcome, all decision strategies produced net cost savings; however, these were significantly higher for the +PET and the +SPECT strategies. CONCLUSION: 18F-FDG PET is cost-effective in the presurgical evaluation, particularly when used in patients with a nonlocalizing or nonconcordant VEM or MRI result.

Dynamic contrast enhanced CT in nodule characterization: How we review and report.

Incidental indeterminate solitary pulmonary nodules (SPN) that measure less than 3 cm in size are an increasingly common finding on computed tomography (CT) worldwide. Once identified there are a number of imaging strategies that can be performed to help with nodule characterization. These include interval CT, dynamic contrast enhanced computed tomography (DCE-CT), (18)F-fluorodeoxyglucose positron emission tomography-computed tomography ((18)F-FDG-PET-CT). To date the most cost effective and efficient non-invasive test or combination of tests for optimal nodule characterization has yet to be determined.DCE-CT is a functional test that involves the acquisition of a dynamic series of images of a nodule before and following the administration of intravenous iodinated contrast medium. This article provides an overview of the current indications and limitations of DCE- CT in nodule characterization and a systematic approach to how to perform, analyse and interpret a DCE-CT scan.

Computed tomography perfusion imaging for therapeutic assessment: has it come of age as a biomarker in oncology?

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.

Heterogeneity of focal breast lesions and surrounding tissue assessed by mammographic texture analysis: preliminary evidence of an association with tumor invasion and estrogen receptor status.

AIM: This pilot study investigates whether heterogeneity in focal breast lesions and surrounding tissue assessed on mammography is potentially related to cancer invasion and hormone receptor status. MATERIALS AND METHODS: Texture analysis (TA) assessed the heterogeneity of focal lesions and their surrounding tissues in digitized mammograms from 11 patients randomly selected from an imaging archive [ductal carcinoma in situ (DCIS) only, n = 4; invasive carcinoma (IC) with DCIS, n = 3; IC only, n = 4]. TA utilized band-pass image filtration to highlight image features at different spatial frequencies (filter values: 1.0-2.5) from fine to coarse texture. The distribution of features in the derived images was quantified using uniformity. RESULTS: Significant differences in uniformity were observed between patient groups for all filter values. With medium scale filtration (filter value = 1.5) pure DCIS was more uniform (median = 0.281) than either DCIS with IC (median = 0.246, p = 0.0102) or IC (median = 0.249, p = 0.0021). Lesions with high levels of estrogen receptor expression were more uniform, most notably with coarse filtration (filter values 2.0 and 2.5, r(s) = 0.812, p = 0.002). Comparison of uniformity values in focal lesions and surrounding tissue showed significant differences between DCIS with or without IC versus IC (p = 0.0009). CONCLUSION: This pilot study shows the potential for computer-based assessments of heterogeneity within focal mammographic lesions and surrounding tissue to identify adverse pathological features in mammographic lesions. The technique warrants further investigation as a possible adjunct to existing computer aided diagnosis systems.

Blending online techniques with traditional face to face teaching methods to deliver final year undergraduate radiology learning content.

AIM: To review the initial experience of blending a variety of online educational techniques with traditional face to face or contact-based teaching methods to deliver final year undergraduate radiology content at a UK Medical School. MATERIALS AND METHODS: The Brighton and Sussex Medical School opened in 2003 and offers a 5-year undergraduate programme, with the final 5 spent in several regional centres. Year 5 involves several core clinical specialities with onsite radiology teaching provided at regional centres in the form of small-group tutorials, imaging seminars and also a one-day course. An online educational module was introduced in 2007 to facilitate equitable delivery of the year 5 curriculum between the regional centres and to support students on placement. This module had a strong radiological emphasis, with a combination of imaging integrated into clinical cases to reflect everyday practice and also dedicated radiology cases. For the second cohort of year 5 students in 2008 two additional online media-rich initiatives were introduced, to complement the online module, comprising imaging tutorials and an online case discussion room. RESULTS: In the first year for the 2007/2008 cohort, 490 cases were written, edited and delivered via the Medical School managed learning environment as part of the online module. 253 cases contained a form of image media, of which 195 cases had a radiological component with a total of 325 radiology images. Important aspects of radiology practice (e.g. consent, patient safety, contrast toxicity, ionising radiation) were also covered. There were 274,000 student hits on cases the first year, with students completing a mean of 169 cases each. High levels of student satisfaction were recorded in relation to the online module and also additional online radiology teaching initiatives. CONCLUSION: Online educational techniques can be effectively blended with other forms of teaching to allow successful undergraduate delivery of radiology. Efficient IT links and good image quality are essential ingredients for successful student/clinician engagement.

Opportunities for PET to deliver clinical benefit in cancer: breast cancer as a paradigm.

The glucose analogue fluorodeoxyglucose (FDG) has demonstrated enhanced uptake in the majority of tumours as a result of increased uptake and fixation by phosphorylation. It is the most widely used radiotracer in positron emission tomography (PET), being used in >90% of scans, and is useful for diagnosis, staging and detection of residual/recurrent cancer. However, there are limits to the utility of FDG, particularly in certain tumour types. The development of new radiotracers to study molecular processes such as proliferation, apoptosis, angiogenesis and hypoxia will complement FDG by providing additional information on the cell biology of tumours. The aim of this paper is to consider how the availability of new tracers, or new applications for existing PET/CT technologies, could deliver clinical benefit in cancer, using breast cancer as a paradigm.

Double vision: an exploration of radiologists' and general practitioners' views on using picture archiving and communication systems (PACS).

This article explores the perspectives of two user groups, general practitioners (GPs) and consultant radiologists (CRs), on the rollout of picture archiving and communications systems (PACS) within acute trusts and eventually to primary care as part of the electronic patient record. Qualitative interviews were conducted with 16 CRs and 31 GPs. Analysis was carried out using a grounded theory approach. Radiologists expressed positive views about the implementation of PACS in secondary care, but were wary of GPs accessing radiological images. GPs expressed concerns about the added burdens that PACS might bring to primary care, but most felt that sharing images with patients could benefit doctor-patient communication and increase patient satisfaction. This study highlights both impediments and pathways to the implementation of PACS in primary care, and illustrates the importance of regarding PACS as socially embedded and users as culturally disparate.

Colorectal cancer: imaging surveillance following resection of primary tumour.

Most patients with colorectal cancer undergo treatment with curative intent and subsequently enter a surveillance programme. The primary aim of surveillance is to identify patients with disease relapse at a resectable stage. However, the identification of local recurrence and metachronous carcinoma are also important aspects of follow up. Patients under observation may be referred for imaging either because regular imaging forms part of the surveillance strategy, or because tumour relapse is suggested by the development of new symptoms or a rise in tumour markers. This paper reviews the use of new and existing imaging techniques during surveillance following resection of primary colorectal cancer. The use of imaging for this surveillance is an application of cancer imaging that is supported by evidence-based clinical guidelines. Computed tomography provides the mainstay modality on grounds of good overall diagnostic performance combined with high availability and low cost. Improvements in survival with more aggressive follow up and treatment are likely to demand more accurate imaging techniques in the future.