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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 (r 2 =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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Stoycheva, Jameel, Bain, Nandi, Jones, Honeyfield, Gedroyc and Moore.)

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 (KOOS 4 ) 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 KOOS 4 . 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 KOOS 4 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 KOOS 4 improved from 38 (SD 18) at baseline to 79 (18) at 2 years. Baseline KOOS 4, medium-to-large knee effusion, and moderate-to-severe synovial blood staining and their interaction significantly predicted 2-year KOOS 4 (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 KOOS 4 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., Competing Interests: TLV reports consultancy fees from GlaxoSmithKline, UCB, and Mundipharma and has also received research grants from Galapagos, Fidia, and Samumed. NKA reports consultancy fees from Pfizer/Lilly and received a grant in a related area of research from Merck. AJ reports consultancy fees from Freshfields Bruckhaus Deringer and from Anthera Pharmaceuticals. AW is a board member and holds stock in Fortius Clinic, has received research grants from Smith and Nephew, is a board member and shareholder in Innovate Orthopaedics, and a shareholder in DocComs. FEW has received clinical study grants from Pfizer and Astellas Pharma, reports consultancy fees from Pfizer, and is part of a consortium receiving some of its research funding from Galapagos, Fidia, and Samumed. All other authors report no competing interests., (© 2021 The Authors. Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license.)

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.

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 K trans , 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.

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 18 F-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 18 F-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 18 F PET; however, this approach provides proof of principle for using different radionuclide tracers and other MRI methods, such as MR perfusion and diffusion.

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., (© The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain.)

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.

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)., (Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

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.

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.

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., (© RSNA, 2010)

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.

Objective: The objective of our study was to investigate whether an increasing number of computer-aided detection (CAD) false-positives decreases reader sensitivity, specificity, and confidence for nonexpert readers of CT colonography (CTC)., Materials and Methods: Fifty CTC data sets (29 men; mean age, 65 years), 25 of which contained 35 polyps > or = 5 mm, were selected in which CAD had 100% polyp sensitivity at two sphericity settings (0 and 75) but differed in the number of false-positives. The data sets were read by five readers twice: once at each sphericity setting. Sensitivity, specificity, report time, and confidence before and after second-read CAD were compared using the paired exact and Student's t test, respectively. Receiver operating characteristic (ROC) curves were generated using reader confidence (1-100) in correct case classification (normal or abnormal)., Results: CAD generated a mean of 42 (range, 3-118) and 15 (range, 1-36) false-positives at a sphericity of 0 and 75, respectively. CAD at both settings increased per-patient sensitivity from 82% to 87% (p = 0.03) and per-polyp sensitivity by 8% and 10% for a sphericity of 0 and 75, respectively (p < 0.001). Specificity decreased from 84% to 79% (sphericity 0 and 75, p = 0.03 and 0.07). There was no difference in sensitivity, specificity, or reader confidence between sphericity settings (p = 1.0, 1.0, 0.11, respectively). The area under the ROC curve was 0.78 (95% CI, 0.70-0.86) and 0.77 (0.68-0.85) for a sphericity of 0 and 75, respectively. CAD added a median of 4.4 minutes (interquartile range [IQR], 2.7-6.5 minutes) and 2.2 minutes (IQR, 1.2-4.0 minutes) for a sphericity of 0 and 75, respectively (p < 0.001). CONCLUSION. CAD has the potential to increase the sensitivity of readers inexperienced with CTC, although specificity may be reduced. An increased number of CAD-generated false-positives does not negate any beneficial effect but does reduce efficiency.

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.

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 (

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.

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.

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

Rational and Objectives: To investigate the effect of colonic distension on polyp measurement accuracy and reader agreement., Materials and Methods: Institutional review board permission was obtained. A sealed colectomy specimen from a patient with familial adenomatous polyposis was scanned using a four-detector-row computed tomography (CT) after half and full air distension. A histopathologist measured the maximum dimension of all polyps in the opened specimen. Digital photographs and line drawings were used to individually match polyps visible in the CT datasets. Two observers (radiologist, technician) independently estimated the maximum polyp diameter using both two-dimensional (2D) and three-dimensional (3D) surface rendering. Full-distension measurements were repeated 1 week later. Accuracy was analyzed using paired t-test. Observer agreement was assessed using Bland Altman limits of agreement., Results: Twenty-three polyps (4-15 mm) were identified. 2D measurements were significantly smaller than histologic size at both half distension (radiologist first): mean difference [md] -1.1 mm, md -1.7 mm, and full distension md -1.1 mm, md 1.4 mm (all P < .001). 3D measurements were not significantly different from true size other than after half distension for the technician (md -0.7 mm, P = .01). 95% Bland Altman limits for interobserver agreement were narrower after full distension, and better using 2D (half-distension span of agreement approximately 4.7 mm and 6 mm for 2D and 3D, respectively). 2D intraobserver span of agreement between half and full distension was approximately 3.8 mm and 3.2 mm for the radiologist and technician, respectively, compared with 6.2 mm and 5.5 mm using 3D., Conclusion: 3D polyp measurement is more accurate than 2D. However, in the presence of suboptimal distension, inter- and intraobserver agreement is superior using 2D.

Purpose: To retrospectively compare primary three-dimensional (3D) endoluminal analysis with primary two-dimensional (2D) transverse analysis supplemented by computer-assisted reader (CAR) software for computed tomographic (CT) polyp detection and reader reporting times., Materials and Methods: Ethical permission and patient consent were obtained from all donor institutions for use of CT colonography data sets. Twenty CT colonography data sets from 14 men (median age, 61 years; age range, 52-78 years) with 48 endoscopically proved polyps were selected. Polyp coordinates were documented in consensus by three unblinded radiologists to create a reference standard. Two radiologists read the data sets, which were randomized between primary 3D endoluminal views with 2D problem solving and 2D views supplemented by CAR software. Reading times and diagnostic confidence were documented. The CAR software highlighted possible polyps by superimposing circles on the 2D transverse images. Data sets were reread after 1 month by using the opposing analysis method. Detection rates were compared by using the McNemar test. Reporting times and diagnostic confidence were compared by using the paired t test and Mann-Whitney U test, respectively., Results: Mean sensitivity values for polyps measuring 1-5, 6-9, and 10 mm or larger were 14%, 53%, and 83%, respectively, for 2D CAR analysis and 16%, 53%, and 67%, respectively, for primary 3D analysis. Overall sensitivity values were 41% for 2D CAR analysis and 39% for primary 3D analysis (P=.77). Reader 1 detected more polyps than reader 2, particularly when using the 3D fly-through method (P=.002). Mean reading times were significantly longer with the 3D method (P=.001). Mean false-positive findings were 1.5 for 2D analysis and 5.5 for 3D analysis. Reader confidence was not significantly different between analysis methods (P=.42)., Conclusion: Two-dimensional CAR analysis is quicker and at least matches the sensitivity of primary 3D endoluminal analysis, with fewer false-positive findings., (Copyright (c) RSNA, 2006.)

Objective: The purpose of our study was to assess the sensitivity of computer-assisted reader (CAR) software for polyp detection compared with the performance of expert reviewers., Materials and Methods: A library of colonoscopically validated CT colonography cases were collated and separated into training and test sets according to the time of accrual. Training data sets were annotated in consensus by three expert radiologists who were aware of the colonoscopy report. A subset of 45 training cases containing 100 polyps underwent batch analysis using ColonCAR version 1.2 software to determine the optimum polyp enhancement filter settings for polyp detection. Twenty-five consecutive positive test data sets were subsequently interpreted individually by each expert, who was unaware of the endoscopy report, and before generation of the annotated reference via an unblinded consensus interpretation. ColonCAR version 1.2 software was applied to the test cases, at optimized polyp enhancement filter settings, to determine diagnostic performance. False-positive findings were classified according to importance., Results: The 25 test cases contained 32 nondiminutive polyps ranging from 6 to 35 mm in diameter. The ColonCAR version 1.2 software identified 26 (81%) of 32 polyps compared with an average sensitivity of 70% for the expert reviewers. Eleven (92%) of 12 polyps > or = 10 mm were detected by ColonCAR version 1.2. All polyps missed by experts 1 (n = 4) and 2 (n = 3) and 12 (86%) of 14 polyps missed by expert 3 were detected by ColonCAR version 1.2. The median number of false-positive highlights per case was 13, of which 91% were easily dismissed., Conclusion: ColonCAR version 1.2 is sensitive for polyp detection, with a clinically acceptable false-positive rate. ColonCAR version 1.2 has a synergistic effect to the reviewer alone, and its standalone performance may exceed even that of experts.

Objective: To investigate inter- and intraobserver agreement of automated measurement of polyp diameter in vitro., Methods: Two phantoms ("QRM" and "Whiting") containing simulated polyps of known diameter and volume were scanned using 16-detector row computed tomography. Two observers estimated polyp diameter using 3 methods: software calipers ("manual"), freehand boundary identification ("semiautomatic"), and automated software segmentation ("fully automatic")., Results: Intraobserver 95% limits of agreement for diameter were narrowest for the fully automatic method (QRM span: 0.39 mm, 0.48 mm; Whiting span: 0.24 mm, 0 mm). Manual estimates were approximately 10 times wider (QRM span: 3.57 mm, 3.21 mm; Whiting span: 3.2 mm, 2.02 mm). Volume estimates were narrowest for the fully automatic method (span: 24.2 mm, 24.1 mm vs. 97.9 mm, 102.9 mm for semiautomatic measurement). Interobserver agreement for diameter was narrowest for the fully automatic method (QRM span: 0.12 mm, Whiting span: 0.16 mm), with the manual method approximately 18 times wider (QRM span: 2.87 mm, Whiting span: 2.18 mm)., Conclusion: Fully automated measurement of polyp diameter and volume is technically feasible and results in superior inter- and intraobserver agreement.