Perioperative research into memory (PRiMe), part 2: Adult burns intensive care patients show altered structure and function of the default mode network.

BACKGROUND: Long-term cognitive impairment (LTCI) is experienced by up to two thirds of patients discharged from burns intensive care units (BICUs), however little is known about its neurobiological basis. This study investigated if patients previously admitted to BICU showed structural and functional MRI changes of the Default Mode Network (DMN). METHODS: Fifteen patients previously admitted to BICU with a significant burns injury, and 15 matched volunteers, underwent structural and functional MRI scans. Functional connectivity, fractional anisotropy and cortical thickness of the main DMN subdivisions (anterior DMN (aDMN), posterior DMN (pDMN) and right (rTPJ) and left (lTPJ) temporo-parietal junctions) were compared between patients and volunteers, with differences correlated against cognitive performance. RESULTS: Functional connectivity between rTPJ and pDMN (t = 2.91, p = 0.011) and between rTPJ and lTPJ (t = 3.18, p = 0.008) was lower in patients compared to volunteers. Functional connectivity between rTPJ and pDMN correlated with cognitive performance (r2 =0.33, p < 0.001). Mean fractional anisotropy of rTPJ (t = 2.70, p = 0.008) and lTPJ (T = 2.39, p = 0.015) was lower in patients but there was no difference in cortical thickness. CONCLUSIONS: Patients previously admitted to BICU show structural and functional disruption of the DMN. Since functional changes correlate with cognitive performance, this should direct further research into intensive-care-related cognitive impairment.

'Am I fixed, am I better now?': undergoing MR-guided focused ultrasound for essential tremor: an interpretative phenomenological analysis.

Introduction: Essential tremor (ET) is characterised by postural and intentional tremor typically affecting the upper limbs, which can negatively impact functionality and quality of life. Magnetic Resonance-guided Focused Ultrasound (MRgFUS) is a novel and promising non-invasive treatment for ET which offers instantaneous results. Methods: Using interpretative phenomenological analysis we explored the experience of undergoing MRgFUS in six ET patients as well as their experiences pre- and post-procedure. Results: One-time, retrospective semi-structured interviews were conducted and six themes emerged: Life pre-treatment: "It's everyday tasks that get you down" and "Most people who understand, they are okay. Some people aren't"; MRgFUS: Treatment day: "Going into the unknown" and "There's no way I was going to press that button"; and Life post-treatment: "One is good. Two is better" and "Am I fixed, am I better now?." Discussion: The findings point to a significant period of adjustment associated with living with ET and the effects of undergoing ET MRgFUS treatment. As ET progressed, participants struggled to cope with increasing symptoms and had to develop coping strategies to manage life with ET. The procedure itself was perceived as strange and extraordinary and despite some immediate adverse effects participants were determined to go through with it. Post procedure, all participants reported tremor suppression which was life changing. While some participants still felt burdened by ET, others expressed it took them a while to psychologically adjust to what essentially was their new body. This study has highlighted the need for patients to be supported at all stages of their ET journey.

Clinical and molecular associations with outcomes at 2 years after acute knee injury: a longitudinal study in the Knee Injury Cohort at the Kennedy (KICK).

BACKGROUND: Joint injury is a major risk factor for osteoarthritis and provides an opportunity to prospectively examine early processes associated with osteoarthritis. We investigated whether predefined baseline demographic and clinical factors, and protein analytes in knee synovial fluid and in plasma or serum, were associated with clinically relevant outcomes at 2 years after knee injury. METHODS: This longitudinal cohort study recruited individuals aged 16-50 years between Nov 1, 2010, and Nov 28, 2014, across six hospitals and clinics in London, UK. Participants were recruited within 8 weeks of having a clinically significant acute knee injury (effusion and structural injury on MRI), which was typically treated surgically. We measured several predefined clinical variables at baseline (eg, time from injury to sampling, extent and type of joint injury, synovial fluid blood staining, presence of effusion, self-reported sex, age, and BMI), and measured 12 synovial fluid and four plasma or serum biomarkers by immunoassay at baseline and 3 months. The primary outcome was Knee Injury and Osteoarthritis Outcome Score (KOOS4) at 2 years, adjusted for baseline score, assessed in all patients. Linear and logistic regression models adjusting for predefined covariates were used to assess associations between baseline variables and 2-year KOOS4. This study is registered with ClinicalTrials.gov, number NCT02667756. FINDINGS: We enrolled 150 patients at a median of 17 days (range 1-59, IQR 9-26) after knee injury. 123 (82%) were male, with a median age of 25 years (range 16-50, IQR 21-30). 98 (65%) of 150 participants completed a KOOS4 at 2 (or 3) years after enrolment (50 participants were lost to follow-up and two were withdrawn due to adverse events unrelated to study participation); 77 (51%) participants had all necessary variables available and were included in the core variable adjusted analysis. In the 2-year dataset mean KOOS4 improved from 38 (SD 18) at baseline to 79 (18) at 2 years. Baseline KOOS4, medium-to-large knee effusion, and moderate-to-severe synovial blood staining and their interaction significantly predicted 2-year KOOS4 (n=77; coefficient -20·5, 95% CI -34·8 to -6·18; p=0·0060). The only predefined biomarkers that showed independent associations with 2-year KOOS4 were synovial fluid MCP-1 (n=77; -0·015, 0·027 to -0·004 per change in 1 pg/mL units; p=0·011) and IL-6 (n=77; -0·0005, -0·0009 to -0·0001 per change in 1 pg/mL units; p=0·017). These biomarkers, combined with the interaction of effusion and blood staining, accounted for 39% of outcome variability. Two adverse events occurred that were linked to study participation, both at the time of blood sampling (one presyncopal episode, one tenderness and pain at the site of venepuncture). INTERPRETATION: The combination of effusion and haemarthrosis was significantly associated with symptomatic outcomes after acute knee injury. The synovial fluid molecular protein response to acute knee injury (best represented by MCP-1 and IL-6) was independently associated with symptomatic outcomes but not with structural outcomes, with the biomarkers overall playing a minor role relative to clinical predictors. The relationship between symptoms and structure after acute knee injury and their apparent dissociation early in this process need to be better understood to make clinical progress. FUNDING: Versus Arthritis, Kennedy Trust for Rheumatology Research, and NIHR Oxford Biomedical Research Centre.

Imaging and Tissue Biomarkers of Choline Metabolism in Diffuse Adult Glioma: 18F-Fluoromethylcholine PET/CT, Magnetic Resonance Spectroscopy, and Choline Kinase α.

The cellular and molecular basis of choline uptake on PET imaging and MRS-visible choline-containing compounds is not well understood. Choline kinase alpha (ChoKα) is an enzyme that phosphorylates choline, an essential step in membrane synthesis. We investigate choline metabolism through 18F-fluoromethylcholine (18F-FMC) PET, MRS, and tissue ChoKα in human glioma. Fourteen patients with a suspected diffuse glioma underwent multimodal 3T MRI and dynamic 18F-FMC PET/CT prior to surgery. Co-registered PET and MRI data were used to target biopsies to regions of high and low choline signal, and immunohistochemistry for ChoKα expression was performed. The 18F-FMC/PET differentiated WHO (World Health Organization) grade IV from grade II and III tumours, whereas MRS differentiated grade III/IV from grade II tumours. Tumoural 18F-FMC/PET uptake was higher than in normal-appearing white matter across all grades and markedly elevated within regions of contrast enhancement. The 18F-FMC/PET correlated weakly with MRS Cho ratios. ChoKα expression on IHC was negative or weak in all but one glioblastoma sample, and did not correlate with tumour grade or imaging choline markers. MRS and 18F-FMC/PET provide complimentary information on glioma choline metabolism. Tracer uptake is, however, potentially confounded by blood-brain barrier permeability. ChoKα overexpression does not appear to be a common feature in diffuse glioma.

Reliability of dynamic contrast-enhanced magnetic resonance imaging data in primary brain tumours: a comparison of Tofts and shutter speed models.

PURPOSE: The purpose of this study is to investigate the robustness of pharmacokinetic modelling of DCE-MRI brain tumour data and to ascertain reliable perfusion parameters through a model selection process and a stability test. METHODS: DCE-MRI data of 14 patients with primary brain tumours were analysed using the Tofts model (TM), the extended Tofts model (ETM), the shutter speed model (SSM) and the extended shutter speed model (ESSM). A no-effect model (NEM) was implemented to assess overfitting of data by the other models. For each lesion, the Akaike Information Criteria (AIC) was used to build a 3D model selection map. The variability of each pharmacokinetic parameter extracted from this map was assessed with a noise propagation procedure, resulting in voxel-wise distributions of the coefficient of variation (CV). RESULTS: The model selection map over all patients showed NEM had the best fit in 35.5% of voxels, followed by ETM (32%), TM (28.2%), SSM (4.3%) and ESSM (< 0.1%). In analysing the reliability of Ktrans, when considering regions with a CV < 20%, ≈ 25% of voxels were found to be stable across all patients. The remaining 75% of voxels were considered unreliable. CONCLUSIONS: The majority of studies quantifying DCE-MRI data in brain tumours only consider a single model and whole tumour statistics for the output parameters. Appropriate model selection, considering tissue biology and its effects on blood brain barrier permeability and exchange conditions, together with an analysis on the reliability and stability of the calculated parameters, is critical in processing robust brain tumour DCE-MRI data.

An MRS- and PET-guided biopsy tool for intraoperative neuronavigational systems.

OBJECTIVE Glioma heterogeneity and the limitations of conventional structural MRI for identifying aggressive tumor components can limit the reliability of stereotactic biopsy and, hence, tumor characterization, which is a hurdle for developing and selecting effective treatment strategies. In vivo MR spectroscopy (MRS) and PET enable noninvasive imaging of cellular metabolism relevant to proliferation and can detect regions of more highly active tumor. Here, the authors integrated presurgical PET and MRS with intraoperative neuronavigation to guide surgical biopsy and tumor sampling of brain gliomas with the aim of improving intraoperative tumor-tissue characterization and imaging biomarker validation. METHODS A novel intraoperative neuronavigation tool was developed as part of a study that aimed to sample high-choline tumor components identified by multivoxel MRS and 18F-methylcholine PET-CT. Spatially coregistered PET and MRS data were integrated into structural data sets and loaded onto an intraoperative neuronavigation system. High and low choline uptake/metabolite regions were represented as color-coded hollow spheres for targeted stereotactic biopsy and tumor sampling. RESULTS The neurosurgeons found the 3D spherical targets readily identifiable on the interactive neuronavigation system. In one case, areas of high mitotic activity were identified on the basis of high 18F-methylcholine uptake and elevated choline ratios found with MRS in an otherwise low-grade tumor, which revealed the possible use of this technique for tumor characterization. CONCLUSIONS These PET and MRI data can be combined and represented usefully for the surgeon in neuronavigation systems. This method enables neurosurgeons to sample tumor regions based on physiological and molecular imaging markers. The technique was applied for characterizing choline metabolism using MRS and 18F PET; however, this approach provides proof of principle for using different radionuclide tracers and other MRI methods, such as MR perfusion and diffusion.

An MRS- and PET-guided biopsy tool for intraoperative neuronavigational systems.

OBJECTIVE Glioma heterogeneity and the limitations of conventional structural MRI for identifying aggressive tumor components can limit the reliability of stereotactic biopsy and, hence, tumor characterization, which is a hurdle for developing and selecting effective treatment strategies. In vivo MR spectroscopy (MRS) and PET enable noninvasive imaging of cellular metabolism relevant to proliferation and can detect regions of more highly active tumor. Here, the authors integrated presurgical PET and MRS with intraoperative neuronavigation to guide surgical biopsy and tumor sampling of brain gliomas with the aim of improving intraoperative tumor-tissue characterization and imaging biomarker validation. METHODS A novel intraoperative neuronavigation tool was developed as part of a study that aimed to sample high-choline tumor components identified by multivoxel MRS and 18F-methylcholine PET-CT. Spatially coregistered PET and MRS data were integrated into structural data sets and loaded onto an intraoperative neuronavigation system. High and low choline uptake/metabolite regions were represented as color-coded hollow spheres for targeted stereotactic biopsy and tumor sampling. RESULTS The neurosurgeons found the 3D spherical targets readily identifiable on the interactive neuronavigation system. In one case, areas of high mitotic activity were identified on the basis of high 18F-methylcholine uptake and elevated choline ratios found with MRS in an otherwise low-grade tumor, which revealed the possible use of this technique for tumor characterization. CONCLUSIONS These PET and MRI data can be combined and represented usefully for the surgeon in neuronavigation systems. This method enables neurosurgeons to sample tumor regions based on physiological and molecular imaging markers. The technique was applied for characterizing choline metabolism using MRS and 18F PET; however, this approach provides proof of principle for using different radionuclide tracers and other MRI methods, such as MR perfusion and diffusion.

Analysis of ageing-associated grey matter volume in patients with multiple sclerosis shows excess atrophy in subcortical regions.

Age of onset in multiple sclerosis (MS) exerts an influence on the course of disease. This study examined whether global and regional brain volumes differed between "younger" and "older" onset MS subjects who were matched for short disease duration, mean 1.9 years and burden as measured by the MS Severity Score and relapses. 21 younger-onset MS subjects (age 30.4 ± 3.2 years) were compared with 17 older-onset (age 48.7 ± 3.3 years) as well as age-matched controls (n = 31, 31.9 ± 3.5 years and n = 21, 47.3 ± 4.0 years). All subjects underwent 3D volumetric T1 and T2-FLAIR imaging. White matter (WM) and grey matter (GM) lesions were outlined manually. Lesions were filled prior to tissue and structural segmentation to reduce classification errors. Volume loss versus control was predominantly in the subcortical GM, at > 13% loss. Younger and older-onset MS subjects had similar, strong excess loss in the putamen, thalamus, and nucleus accumbens. No excess loss was detected in the amygdala or pallidum. The hippocampus and caudate showed significant excess loss in the younger group (p < 0.001) and a strong trend in the older-onset group. These results provide a potential imaging correlate of published neuropsychological studies that reported the association of younger age at disease onset with impaired cognitive performance, including decreased working memory.

Disconnection between the default mode network and medial temporal lobes in post-traumatic amnesia.

SEE BIGLER DOI101093/AWW277 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Post-traumatic amnesia is very common immediately after traumatic brain injury. It is characterized by a confused, agitated state and a pronounced inability to encode new memories and sustain attention. Clinically, post-traumatic amnesia is an important predictor of functional outcome. However, despite its prevalence and functional importance, the pathophysiology of post-traumatic amnesia is not understood. Memory processing relies on limbic structures such as the hippocampus, parahippocampus and parts of the cingulate cortex. These structures are connected within an intrinsic connectivity network, the default mode network. Interactions within the default mode network can be assessed using resting state functional magnetic resonance imaging, which can be acquired in confused patients unable to perform tasks in the scanner. Here we used this approach to test the hypothesis that the mnemonic symptoms of post-traumatic amnesia are caused by functional disconnection within the default mode network. We assessed whether the hippocampus and parahippocampus showed evidence of transient disconnection from cortical brain regions involved in memory processing. Nineteen patients with traumatic brain injury were classified into post-traumatic amnesia and traumatic brain injury control groups, based on their performance on a paired associates learning task. Cognitive function was also assessed with a detailed neuropsychological test battery. Functional interactions between brain regions were investigated using resting-state functional magnetic resonance imaging. Together with impairments in associative memory, patients in post-traumatic amnesia demonstrated impairments in information processing speed and spatial working memory. Patients in post-traumatic amnesia showed abnormal functional connectivity between the parahippocampal gyrus and posterior cingulate cortex. The strength of this functional connection correlated with both associative memory and information processing speed and normalized when these functions improved. We have previously shown abnormally high posterior cingulate cortex connectivity in the chronic phase after traumatic brain injury, and this abnormality was also observed in patients with post-traumatic amnesia. Patients with post-traumatic amnesia showed evidence of widespread traumatic axonal injury measured using diffusion magnetic resonance imaging. This change was more marked within the cingulum bundle, the tract connecting the parahippocampal gyrus to the posterior cingulate cortex. These findings provide novel insights into the pathophysiology of post-traumatic amnesia and evidence that memory impairment acutely after traumatic brain injury results from altered parahippocampal functional connectivity, perhaps secondary to the effects of axonal injury on white matter tracts connecting limbic structures involved in memory processing.

A Randomised Comparison Evaluating Changes in Bone Mineral Density in Advanced Prostate Cancer: Luteinising Hormone-releasing Hormone Agonists Versus Transdermal Oestradiol.

BACKGROUND: Luteinising hormone-releasing hormone agonists (LHRHa), used as androgen deprivation therapy (ADT) in prostate cancer (PCa) management, reduce serum oestradiol as well as testosterone, causing bone mineral density (BMD) loss. Transdermal oestradiol is a potential alternative to LHRHa. OBJECTIVE: To compare BMD change in men receiving either LHRHa or oestradiol patches (OP). DESIGN, SETTING, AND PARTICIPANTS: Men with locally advanced or metastatic PCa participating in the randomised UK Prostate Adenocarcinoma TransCutaneous Hormones (PATCH) trial (allocation ratio of 1:2 for LHRHa:OP, 2006-2011; 1:1, thereafter) were recruited into a BMD study (2006-2012). Dual-energy x-ray absorptiometry scans were performed at baseline, 1 yr, and 2 yr. INTERVENTIONS: LHRHa as per local practice, OP (FemSeven 100µg/24h patches). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was 1-yr change in lumbar spine (LS) BMD from baseline compared between randomised arms using analysis of covariance. RESULTS AND LIMITATIONS: A total of 74 eligible men (LHRHa 28, OP 46) participated from seven centres. Baseline clinical characteristics and 3-mo castration rates (testosterone ≤1.7 nmol/l, LHRHa 96% [26 of 27], OP 96% [43 of 45]) were similar between arms. Mean 1-yr change in LS BMD was -0.021g/cm(3) for patients randomised to the LHRHa arm (mean percentage change -1.4%) and +0.069g/cm(3) for the OP arm (+6.0%; p<0.001). Similar patterns were seen in hip and total body measurements. The largest difference between arms was at 2 yr for those remaining on allocated treatment only: LS BMD mean percentage change LHRHa -3.0% and OP +7.9% (p<0.001). CONCLUSIONS: Transdermal oestradiol as a single agent produces castration levels of testosterone while mitigating BMD loss. These early data provide further supporting evidence for the ongoing phase 3 trial. PATIENT SUMMARY: This study found that prostate cancer patients treated with transdermal oestradiol for hormonal therapy did not experience the loss in bone mineral density seen with luteinising hormone-releasing hormone agonists. Other clinical outcomes for this treatment approach are being evaluated in the ongoing PATCH trial. TRIAL REGISTRATION: ISRCTN70406718, PATCH trial (ClinicalTrials.gov NCT00303784).

Contemporary hormone therapy with LHRH agonists for prostate cancer: avoiding osteoporosis and fracture.

INTRODUCTION: Prostate cancer is a large clinical burden across Europe. It is, in fact, the most common cancer in males, accounting for more than 92,300 deaths annually throughout the continent. Prostate cancer is androgen-sensitive; thus an androgen deprivation therapy (ADT) is often used for treatment by reducing androgen to castrate levels. Several ADT agents have achieved benefits with effective palliation, but, unfortunately, severe adverse events are frequent. Contemporary ADT (Luteinising Hormone Releasing Hormone agonist - LHRHa injections) can result in side effects that include osteoporosis and fractures, compromising quality of life and survival. METHODS: In this review we analysed the associated bone toxicity consequent upon contemporary ADT and based on the literature and our own experience we present future perspectives that seek to mitigate this associated toxicity both by development of novel therapies and by better identification and prediction of fracture risk. RESULTS: Preliminary results indicate that parenteral oestrogen can mitigate associated osteoporotic risk and that CT scans could provide a more accurate indicator of overall bone quality and hence fracture risk. CONCLUSIONS: As healthcare costs increase globally, cheap and effective alternatives that achieve ADT, but mitigate or avoid such bone toxicities, will be needed. More so, innovative techniques to improve both the measurement and the extent of this toxicity, by assessing bone health and prediction of fracture risk, are also required.

Apparent Diffusion Coefficient of Normal Abdominal Organs and Bone Marrow From Whole-Body DWI at 1.5 T: The Effect of Sex and Age.

OBJECTIVE: The objectives of this study were to define the range of apparent diffusion coefficients (ADCs) from whole-body DWI in normal abdominal organs and bone marrow, to identify ADC differences between sexes and changes occurring with age, and to evaluate the effect of the fat fraction (FF) on the ADC of normal liver parenchyma and bone marrow. MATERIALS AND METHODS: Fifty-one healthy volunteers (mean age = 38 years; age range = 23-68 years) underwent whole-body DWI using single-shot echo-planar imaging (b = 0, 150, 400, 750, and 1000 s/mm(2)). A two-point Dixon technique was used to evaluate the FF. Perfusion-sensitive ADCs, which we refer to as "ADCALL," and perfusion-insensitive ADCs, which we refer to as "ADCHIGH," of the liver and renal parenchyma, spleen, pancreatic tail, and red and yellow bone marrow were calculated. The relationships between ADC and sex, age, and FF were examined. RESULTS: ADCALL and ADCHIGH were significantly higher in female volunteers for the pancreatic tail (p = 0.046 and 0.008, respectively), red bone marrow (p = 0.029 and 0.001), and yellow bone marrow (p < 0.001 for both) but with considerable overlap. There were significant negative correlations between ADCALL and ADCHIGH and age in the liver parenchyma (p = 0.008 and 0.01, respectively) and in the yellow bone marrow (p = 0.013 and 0.039) for all subjects. ADCALL and ADCHIGH were also negatively correlated with FF in the liver parenchyma (p = 0.006 and 0.008, respectively) and in yellow bone marrow (p < 0.001 and p = 0.001) in all subjects. CONCLUSION: The ADCs of normal liver parenchyma and bone marrow change significantly with age. The ADCs of bone marrow in women are significantly higher than those of men and correlate strongly with FF. These effects may have an impact on image interpretation when using whole-body DWI to assess disease burden and treatment response.

Night-time immobilization of the distal interphalangeal joint reduces pain and extension deformity in hand osteoarthritis.

OBJECTIVE: DIP joint OA is common but has few cost-effective, evidence-based interventions. Pain and deformity [radial or ulnar deviation of the joint or loss of full extension (extension lag)] frequently lead to functional and cosmetic issues. We investigated whether splinting the DIP joint would improve pain, function and deformity. METHODS: A prospective, radiologist-blinded, non-randomized, internally controlled trial of custom splinting of the DIP joint was carried out. Twenty-six subjects with painful, deforming DIP joint hand OA gave written, informed consent. One intervention joint and one control joint were nominated. A custom gutter splint was worn nightly for 3 months on the intervention joint, with clinical and radiological assessment at baseline, 3 and 6 months. Differences in the change were compared by the Wilcoxon signed rank test. RESULTS: The median average pain at baseline was similar in the intervention (6/10) and control joints (5/10). Average pain (primary outcome measure) and worst pain in the intervention joint were significantly lower at 3 months compared with baseline (P = 0.002, P = 0.02). Differences between intervention and control joint average pain reached significance at 6 months (P = 0.049). Extension lag deformity was significantly improved in intervention joints at 3 months and in splinted joints compared with matched contralateral joints (P = 0.016). CONCLUSION: Short-term night-time DIP joint splinting is a safe, simple treatment modality that reduces DIP joint pain and improves extension of the digit, and does not appear to give rise to non-compliance, increased stiffness or joint restriction. TRIAL REGISTRATION: clinical trials.gov, http://clinicaltrials.gov, NCT01249391.

Incremental benefit of computer-aided detection when used as a second and concurrent reader of CT colonographic data: multiobserver study.

PURPOSE: To quantify the changes in reader performance levels, if any, during interpretation of computed tomographic (CT) colonographic data when a computer-aided detection (CAD) system is used as a second or concurrent reader. MATERIALS AND METHODS: After institutional review board approval was obtained, 16 experienced radiologists searched for polyps in 112 patients, 56 of whom had 132 polyps. Each case was interpreted on three separate occasions by using an unassisted (without CAD), second-read CAD, or concurrent CAD reading paradigm. The reading paradigm and case order were randomized, with a minimal interval of 1 month between consecutive interpretations. The readers' findings were compared with the reference-truth interpretation. The mean per-patient sensitivity and mean per-patient specificity with CAD were compared with those achieved with unassisted reading. An increase in per-patient sensitivity was considered to be clinically more important than an equivalent decrease in specificity. RESULTS: The mean per-patient sensitivity for identification of patients with polyps of any size increased significantly with use of second-read CAD (mean increase, 7.0%; 95% confidence interval [CI]: 4.0%, 9.8%) and concurrent CAD (mean increase, 4.5%; 95% CI: 0.8%, 8.2%). The mean per-patient specificity did not decrease significantly with use of second-read CAD (mean decrease, -2.5%; 95% CI: -5.2%, 0.1%) or concurrent CAD (mean decrease, -2.2%; 95% CI: -4.6%, 0.2%). With analysis restricted to patients with polyps 6 mm or larger, the benefit in sensitivity with second-read CAD remained (mean increase, 7.1%; 95% CI: 3.0%, 11.1%), whereas the increase with concurrent CAD was not significant (mean increase, 4.2%; 95% CI: -0.5%, 8.9%). Use of second-read CAD significantly increased the per-polyp sensitivity for polyps 6 mm or larger (mean increase, 9.0%; 98.3% CI: 4.9%, 12.8%) and polyps 5 mm or smaller (mean increase, 5.9%; 98.3% CI: 3.2%, 9.1%), but use of concurrent CAD increased the per-polyp sensitivity for only those polyps 5 mm or smaller (mean increase, 4.8%; 98.3% CI: 2.2%, 7.9%). CONCLUSION: Use of second-read CAD significantly improves readers' per-patient and per-polyp detection. Concurrent CAD is less effective. SUPPLEMENTAL MATERIAL: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.10100354/-/DC1.

Polyp characteristics correctly annotated by computer-aided detection software but ignored by reporting radiologists during CT colonography.

PURPOSE: To retrospectively describe the characteristics of polyps incorrectly dismissed by radiologists despite appropriate computer-aided detection (CAD) prompting during computed tomographic (CT) colonography. MATERIALS AND METHODS: Ethics committee approval and patient informed consent were obtained from institutions that provided the data sets used in this HIPAA-compliant study. A total of 111 polyps that had a diameter of at least 6 mm and were detected with CAD were collated from three previous studies in which researchers investigated radiologist performance with and without CAD (total, 25 readers). Two new observers graded each polyp with predefined criteria, including polyp size, morphology, and location; data set quality; ease of visualization; tagging use and polyp coating; colonic curvature; CAD mark obscuration; and number of false-positive findings. The 86 polyps that were missed before CAD (those that were unreported by one or more original readers) were divided into those that remained unreported after CAD (no CAD gain, n = 36) and those that were reported correctly by at least one additional reader (CAD gain, n = 50). Logistic-regression analysis and the Fisher exact and Mann-Whitney tests were used to compare the results of both groups with each other and with a control group of 25 polyps, all of which were detected by readers without CAD. RESULTS: Before CAD, polyps 10 mm in diameter or larger, those that were rated easy to visualize, and those that were uncoated by tagged fluid were less likely to be missed (72%, 76%, and 80% of control polyps vs 43%, 43%, and 59% of missed polyps, respectively; P < .001, P < .01, and P < .03, respectively). After CAD, the odds of CAD gain decreased with increasing polyp size (odds ratio, 0.92; 95% confidence interval: 0.85, 1.00; P = .04) and irregular morphology (odds ratio, 0.28; 95% confidence interval: 0.08, 0.92; P = .04). CONCLUSION: Larger irregular polyps are a common source of incorrect radiologist dismissal, despite correct CAD prompting.

Computer assisted detection software for CT colonography: effect of sphericity filter on performance characteristics for patients with and without fecal tagging.

The aim of this study is to investigate the effect of changing sphericity filter values on performance of a computer assisted detection (CAD) system for CT colonography for data with and without fecal tagging. Colonography data from 138 patients with 317 validated polyps were divided into those with (86) and without (52) fecal tagging. Polyp coordinates were established by three observers and datasets analysed subsequently by a proprietary CAD system used at four discrete sphericity filter settings. Prompts were compared with the known coordinates in order to determine sensitivity and specificity. Sensitivity was highest at low sphericity; of 164 polyps 6 mm or more, 144 (87.8%) were detected at sphericity 0.3, and 132 (80.1%) at sphericity 0.9. Of 42 polyps measuring 10 mm or more, 40 (95.2%) were detected at sphericity 0.3, and 36 (85.7%) at sphericity 0.9. There was no significant difference in sensitivity for tagged and un-tagged data but specificity was reduced in tagged data at low sphericity and significantly reduced in untagged data at high sphericity. CAD had a sensitivity of 95.2% for polyps measuring 1 cm or more and 87.8% for polyps 6 mm or more when used at a sphericity setting of 0.3. Higher sphericity settings increased specificity while reducing sensitivity. The bowel preparation used significantly impacts on specificity.

CT colonography: automated measurement of colonic polyps compared with manual techniques--human in vitro study.

PURPOSE: To prospectively investigate the relative accuracy and reproducibility of manual and automated computer software measurements by using polyps of known size in a human colectomy specimen. MATERIALS AND METHODS: Institutional review board approval was obtained for the study; written consent for use of the surgical specimen was obtained. A colectomy specimen containing 27 polyps from a 16-year-old male patient with familial adenomatous polyposis was insufflated, submerged in a container with solution, and scanned at four-section multi-detector row computed tomography (CT). A histopathologist measured the maximum dimension of all polyps in the opened specimen. Digital photographs and line drawings were produced to aid CT-histologic measurement correlation. A novice (radiographic technician) and an experienced (radiologist) observer independently estimated polyp diameter with three methods: manual two-dimensional (2D) and manual three-dimensional (3D) measurement with software calipers and automated measurement with software (automatic). Data were analyzed with paired t tests and Bland-Altman limits of agreement. RESULTS: Seven polyps (

Computed tomographic colonography: assessment of radiologist performance with and without computer-aided detection.

BACKGROUND & AIMS: In isolation, computer-aided detection (CAD) for computed tomographic (CT) colonography is as effective as optical colonoscopy for detection of significant adenomas. However, the unavoidable interaction between CAD and the reader has not been addressed. METHODS: Ten readers trained in CT but without special expertise in colonography interpreted CT colonography images of 107 patients (60 with 142 polyps), first without CAD and then with CAD after temporal separation of 2 months. Per-patient and per-polyp detection were determined by comparing responses with known patient status. RESULTS: With CAD, 41 (68%; 95% confidence interval [CI], 55%-80%) of the 60 patients with polyps were identified more frequently by readers. Per-patient sensitivity increased significantly in 70% of readers, while specificity dropped significantly in only one. Polyp detection increased significantly with CAD; on average, 12 more polyps were detected by each reader (9.1%, 95% CI, 5.2%-12.8%). Small- (< or =5 mm) and medium-sized (6-9 mm) polyps were significantly more likely to be detected when prompted correctly by CAD. However, overall performance was relatively poor; even with CAD, on average readers detected only 10 polyps (51.0%) > or =10 mm and 24 (38.2%) > or =6 mm. Interpretation time was shortened significantly with CAD: by 1.9 minutes (95% CI, 1.4-2.4 minutes) for patients with polyps and by 2.9 minutes (95% CI, 2.5-3.3 minutes) for patients without. Overall, 9 readers (90%) benefited significantly from CAD, either by increased sensitivity and/or by reduced interpretation time. CONCLUSIONS: CAD for CT colonography significantly increases per-patient and per-polyp detection and significantly reduces interpretation times but cannot substitute for adequate training.

CT colonography interpretation times: effect of reader experience, fatigue, and scan findings in a multi-centre setting.

Our purpose was to assess the effect of reader experience, fatigue, and scan findings on interpretation time for CT colonography. Nine radiologists (experienced in CT colonography); nine radiologists and ten technicians (both groups trained using 50 validated examinations) read 40 cases (50% abnormal) under controlled conditions. Individual interpretation times for each case were recorded, and differences between groups determined. Multi-level linear regression was used to investigate effect of scan category (normal or abnormal) and observer fatigue on interpretation times. Experienced radiologists (mean time 10.9 min, SD 5.2) reported significantly faster than less experienced radiologists and technicians; odds ratios of reporting times 1.4 (CI 1.1, 1.8) and 1.6 (1.3, 2.0), respectively (P

Polyp measurement and size categorisation by CT colonography: effect of observer experience in a multi-centre setting.

The extent measurement error on CT colonography influences polyp categorisation according to established management guidelines is studied using twenty-eight observers of varying experience to classify polyps seen at CT colonography as either 'medium' (maximal diameter 6-9 mm) or 'large' (maximal diameter 10 mm or larger). Comparison was then made with the reference diameter obtained in each patient via colonoscopy. The Bland-Altman method was used to assess agreement between observer measurements and colonoscopy, and differences in measurement and categorisation was assessed using Kruskal-Wallis and Chi-squared test statistics respectively. Observer measurements on average underestimated the diameter of polyps when compared to the reference value, by approximately 2-3 mm, irrespective of observer experience. Ninety-five percent limits of agreement were relatively wide for all observer groups, and had sufficient span to encompass different size categories for polyps. There were 167 polyp observations and 135 (81%) were correctly categorised. Of the 32 observations that were miscategorised, 5 (16%) were overestimations and 27 (84%) were underestimations (i.e. large polyps misclassified as medium). Caution should be exercised for polyps whose colonographic diameter is below but close to the 1-cm boundary threshold in order to avoid potential miscategorisation of advanced adenomas.