Imaging in the Age of Precision Medicine: Summary of the Proceedings of the 10th Biannual Symposium of the International Society for Strategic Studies in Radiology.

During the past decade, with its breakthroughs in systems biology, precision medicine (PM) has emerged as a novel health-care paradigm. Challenging reductionism and broad-based approaches in medicine, PM is an approach for disease treatment and prevention that takes into account individual variability in genes, environment, and lifestyle. It involves integrating information from multiple sources in a holistic manner to achieve a definitive diagnosis, focused treatment, and adequate response assessment. Biomedical imaging and imaging-guided interventions, which provide multiparametric morphologic and functional information and enable focused, minimally invasive treatments, are key elements in the infrastructure needed for PM. The emerging discipline of radiogenomics, which links genotypic information to phenotypic disease manifestations at imaging, should also greatly contribute to patient-tailored care. Because of the growing volume and complexity of imaging data, decision-support algorithms will be required to help physicians apply the most essential patient data for optimal management. These innovations will challenge traditional concepts of health care and business models. Reimbursement policies and quality assurance measures will have to be reconsidered and adapted. In their 10th biannual symposium, which was held in August 2013, the members of the International Society for Strategic Studies in Radiology discussed the opportunities and challenges arising for the imaging community with the transition to PM. This article summarizes the discussions and central messages of the symposium.

Radiological journals in the online world: should we think Open? A response.

This discussion on developments within publishing presents further thought on green, gold and hybrid models of open access. It also discusses some of the advantages and disadvantages which may be encountered by researchers, authors, institutions, scientific organisations and publishers.

Standardising measurement of tumour vascularity by imaging: recommendations for ultrasound, computed tomography, magnetic resonance imaging and positron emission tomography.

This review analyses the need for, and likely impact of, four subsequent papers which discuss the importance of standardisation of ultrasound (US), computed tomography (CT), magnetic resonance imaging (MRI) and positron emission tomography (PET) when assessing tumour vascularity. This is particularly important when measuring the vascular effects of therapeutic agents in oncological research and practice. As imaging inexorably moves from the subjective interpretative art-form of the past into its modern role as a fully fledged objective scientific discipline, it is incumbent on all radiologists to understand the need for strict adherence to perceived best practice when evaluating lesions as part of trials. Indeed trials may only be funded by pharmaceutical companies and other grant-giving bodies if rigorous adherence to imaging protocols and quality assurance is in place. Key Points • Various imaging methods can now robustly assess tumour vascular support. • US, CT, MRI and PET are increasingly used to assess tumour vascularity. • These techniques have reached technical maturity for use in therapeutic oncological trials. • Consensus guidelines about using these techniques in assessing tumour vascularity are introduced. • Image acquisition protocols and quality assurance must be established for large trials.

Editorial for anniversary issue of European Radiology.

This special anniversary issue of European Radiology illustrates the wide range of topics which this journal now covers and charts some of the key recent advances in radiology over the last two decades. It includes several review articles in which each author considers some recent groundbreaking papers published in this journal and relates them to developments within their area of interest.

A pilot study to assess the feasibility of measurement of adrenal gland volume by magnetic resonance imaging.

BACKGROUND: Repeated computed tomography (CT) assessment of the adrenal glands is associated with a significant radiation burden. The increasing capabilities of magnetic resonance (MR) volumetric analysis of the adrenals make this a potentially alternative technique in man. PURPOSE: To determine whether MR imaging could be used to measure adrenal volume, and to determine the intra- and interobserver variation and repeatability of MR volume imaging of adrenals in healthy human subjects. MATERIAL AND METHODS: This was a single-cohort, sequential design, three-part study involving four MRI examinations per subject following ethical approval and informed consent. Information was collected on four healthy subjects (three male and one female). Two different investigators estimated the area of the adrenal gland for each of the 3-mm contiguous slices (and consequently adrenal volume). In order to estimate inter- and intrareader variability, a repeated-measures mixed model was fitted with adrenal volume as the dependent variable. In order to estimate any bias between readers, Bland-Altman methodology was applied. RESULTS: Intraobserver variation for adrenal gland volume is approximately 5% of a 3-cm(3 )adrenal gland. Interobserver variation is approximately 9% of a 3-cm(3) adrenal gland. Potential variation in measurement for adrenal volume from all sources equates to approximately 14% of a 3-cm(3) adrenal gland. Verification of image reading by a second investigator (consensus reading) reduces variability. CONCLUSION: Analysis of adrenal gland volume using MRI is a potentially reliable technique that could be used to assess a pathological change in adrenal size.

Unexpected changes in clinical diagnosis: early abdomino-pelvic computed tomography compared with clinical evaluation.

BACKGROUND: To evaluate the value of early computed tomography (CT) on identifying clinically "unexpected" diagnosis in patients presenting with "non specific" acute abdominal pain. MATERIALS AND METHODS: All patients presenting to on-call surgeons with acute abdominal pain were eligible study participants. Patients were randomised to CT within one hour of admission or supine abdominal and erect chest radiography. Ninety-nine patients randomized to CT arm were reviewed for the purpose of this study. The number and severity of unexpected and/or incidental diagnoses detected on the CT were assessed. RESULTS: In 20 of the 99 patients CT revealed primary or secondary diagnoses, which were unexpected following the initial clinical examination and led to completely different therapeutic options. In 15 of those 20 patients CT revealed clinically unexpected conditions, whereas in two patients severe complications of the clinically suspected diagnosis were detected on CT. Five patients had significant incidental findings in addition to their primary diagnosis on CT. In two of these patient CT also revealed clinically unexpected diagnoses. CONCLUSION: Early CT has the advantage of detecting unexpected clinically significant primary and secondary diagnoses in patients presenting with acute abdominal pain and best guides the surgeon to the appropriate patient management.

Lossy 3D JPEG2000 compression of abdominal CT images in patients with acute abdominal complaints: effect of compression ratio on diagnostic confidence and accuracy.

PURPOSE: To retrospectively assess the effect of lossy three-dimensional (3D) Joint Photographic Experts Group 2000 (JPEG2000) compression on diagnostic confidence and diagnostic accuracy at emergency abdominal computed tomography (CT). MATERIALS AND METHODS: In this institutional review board-approved study, transverse images from 104 consecutive multidetector CT examinations (section thickness, 3 mm; reconstruction interval, 2 mm) in patients with acute abdominal complaints were subjected to lossy 3D JPEG2000 compression by using three compression ratios (10:1, 12.5:1, and 15:1, with reference to 384 kB [12 bits] as original image size). Three radiologists independently read the original and compressed CT studies. Patient order and compression ratios were randomized, and readers were blinded to that information. For each organ, the presence of compression artifacts, the diagnosis, the confidence in the diagnosis according to a five-point scale, and the confidence about negative findings were noted. All diagnoses were compared with a standard of reference constructed by an abdominal CT expert by using the original images, surgical reports, and patient follow-up data. Logistic regressions, the Friedman test, and analysis of variance were used for statistical analysis. RESULTS: Primary diagnoses were correct in 91.3% (463 of 507), 90.5% (459 of 507), 89.0% (451 of 507) and 90.1% (457 of 507) of the total number of primary diagnoses at 1:1, 1:10, 1:12.5 and 15:1, respectively. These values did not vary significantly (P = .456) with compression ratios. The radiologists' mean confidence about the primary diagnoses was also almost identical at different compression ratios (4.83, 4.87, 4.77, and 4.84 at 1:1, 1:10, 1:12.5 and 15:1, respectively). However, the radiologists' mean confidence about negative findings in the liver was reduced in 50.3% (157 of 312) of studies at 15:1. CONCLUSION: Diagnostic accuracy was not impaired at compression ratios up to 15:1. However, because of the significant reduction of the confidence about negative findings at 15:1, compression ratios no higher than 12.5:1 are recommended.

An international survey of hospital practice in the imaging of acute scaphoid trauma.

OBJECTIVE: Scaphoid fractures are relatively common. If not treated promptly there may be risk of long-term disability. However, unnecessary wrist immobilization is inconvenient and may hinder professional activities. Therefore, early accurate diagnosis is essential. Currently, the American College of Radiology deems MRI and radiographs as the most appropriate investigations in imaging acute scaphoid trauma. Our objective was to assess scaphoid imaging protocols. MATERIALS AND METHODS: To assess scaphoid imaging protocols, an international survey of imaging practice was performed. Two hundred hospitals worldwide were sent a survey regarding their scaphoid trauma imaging protocols. Only replies from hospitals that had full CT, MRI, and scintigraphy facilities were accepted. RESULTS: Data were obtained from 105 hospitals, of which 23 had fixed protocols. The number of scaphoid radiographic views varied from two to six. Before second-line investigations were initiated, repeat radiographs were usually performed in 76 of the 105 hospitals. In 29 hospitals, other imaging techniques were used without further radiography. The usual second-line investigation was MRI in 31/105, CT in 19/105, and scintigraphy in 14/105. Further protocols included CT or MRI in 10/105, CT or scintigraphy in 6/105, scintigraphy or MRI in 6/105, CT then MRI (if CT was negative) in 1/105, both CT and scintigraphy in 1/105, and scintigraphy then CT (if positive) in 1/105. There was equal preference among MRI, CT, and scintigraphy in 10/105 centers, and clinical examination and radiographs were used alone in 6/105. CONCLUSION: The survey reveals marked inconsistency in the imaging of acute scaphoid injury. Although other factors may have played a role, limited scientific evidence regarding the ideal imaging in acute scaphoid trauma may be the root of this inconsistency.

A test of performance of breast MRI interpretation in a multicentre screening study.

OBJECTIVES: The aim of this study was to assess the consistency and performance of radiologists interpreting breast magnetic resonance imaging (MRI) examinations. MATERIALS AND METHODS: Two test sets of eight cases comprising cancers, benign disease, technical problems and parenchymal enhancement were prepared from two manufacturers' equipment (X and Y) and reported by 15 radiologists using the recording form and scoring system of the UK MRI breast screening study [(MAgnetic Resonance Imaging in Breast Screening (MARIBS)]. Variations in assessments of morphology, kinetic scores and diagnosis were measured by assessing intraobserver and interobserver variability and agreement. The sensitivity and specificity of reporting performances was determined using receiver operating characteristic (ROC) curve analysis. RESULTS: Intraobserver variation was seen in 13 (27.7%) of 47 of the radiologists' conclusions (four technical and seven pathological differences). Substantial interobserver variation was observed in the scores recorded for morphology, pattern of enhancement, quantification of enhancement and washout pattern. The overall sensitivity of breast MRI was high [88.6%, 95% confidence interval (CI) 77.4-94.7%], combined with a specificity of 69.2% (95% CI 60.5-76.7%). The sensitivities were similar for the two test sets (P=.3), but the specificity was significantly higher for the Manufacturer X dataset (P<.001). ROC curve analysis gave an area under the curve of 0.85 (95% CI 0.79-0.92) CONCLUSIONS: Substantial variation in all elements of the scoring system and in the overall diagnostic conclusions was observed between radiologists participating in MARIBS. High overall sensitivity was achieved with moderate specificity. Manufacturer-related differences in specificities possibly occurred because the numerical thresholds set for the scoring system were not optimised for both equipment manufacturers. Scoring systems developed on one equipment software may not be transferable to other manufacturers.

Human metabolic syndrome resulting from dominant-negative mutations in the nuclear receptor peroxisome proliferator-activated receptor-gamma.

We previously reported a syndrome of severe hyperinsulinemia and early-onset hypertension in three patients with dominant-negative mutations in the nuclear hormone receptor peroxisome proliferator-activated receptor (PPAR)-gamma. We now report the results of further detailed pathophysiological evaluation of these subjects, the identification of affected prepubertal children within one of the original families, and the effects of thiazolidinedione therapy in two subjects. These studies 1) definitively demonstrate the presence of severe peripheral and hepatic insulin resistance in the affected subjects; 2) describe a stereotyped pattern of partial lipodystrophy associated with all the features of the metabolic syndrome and nonalcoholic steatohepatitis; 3) document abnormalities in the in vivo function of remaining adipose tissue, including the inability of subcutaneous abdominal adipose tissue to trap and store free fatty acids postprandially and the presence of very low circulating levels of adiponectin; 4) document the presence of severe hyperinsulinemia in prepubertal carriers of the proline-467-leucine (P467L) PPAR-gamma mutation; 5) provide the first direct evidence of cellular resistance to PPAR-gamma agonists in mononuclear cells derived from the patients; and 6) report on the metabolic response to thiazolidinedione therapy in two affected subjects. Although the condition is rare, the study of humans with dominant-negative mutations in PPAR-gamma can provide important insight into the roles of this nuclear receptor in human metabolism.

Primary care referrals for lumbar spine radiography: diagnostic yield and clinical guidelines.

BACKGROUND: Primary care requests for radiographs of the lumbar spine have come under increasing scrutiny. Guidelines aiming to reduce unnecessary radiographs by limiting referrals to patients at high risk of serious disease have been widely distributed. Trial evidence suggests that guidelines can reduce radiography referrals. It is not clear whether this reduction has been achieved in routine practice. AIM: This study, using routine data, was conducted to measure trends in pnmary care referrals for lumbar spine radiography at two hospitals between 1994 and 1999. DESIGN OF STUDY: Analysis of primary care requests for lumbar spine radiography from computerised records. SETTING: Addenbrooke's Hospital, Cambridge (1 July 1994 to 30 June 1999), and Ipswich General Hospital (1 July 1995 to 30 June 1999), United Kingdom. METHOD: All primary care requests for lumbar radiography were identified electronically from computerised information systems. A random sample of 2100 radiography reports were classified according to clinical importance. These classifications were used to examine whether the proportion of radiographs demonstrating potentially more serious findings had increased between 1994 and 1999. RESULTS: There was no evidence that primary care referrals for radiography of the lumbar spine had decreased between 1994 and 1999 at either hospital. General practitioners did not progressively refer more high-risk patients for lumbar radiography. Only a small proportion of patients had important radiographic findings that might warrant specialist referral or specific therapy. CONCLUSION: The implementation of diagnostic guidelines offers much to the NHS. However in these two hospitals, the reduction in radiograph utilisation evident in trials was not achieved. Guideline development is a resource intensive process; distribution must be supported by more effective implementation strategies.

Mosaic overgrowth with fibroadipose hyperplasia is caused by somatic activating mutations in PIK3CA.

The phosphatidylinositol 3-kinase (PI3K)-AKT signaling pathway is critical for cellular growth and metabolism. Correspondingly, loss of function of PTEN, a negative regulator of PI3K, or activating mutations in AKT1, AKT2 or AKT3 have been found in distinct disorders featuring overgrowth or hypoglycemia. We performed exome sequencing of DNA from unaffected and affected cells from an individual with an unclassified syndrome of congenital progressive segmental overgrowth of fibrous and adipose tissue and bone and identified the cancer-associated mutation encoding p.His1047Leu in PIK3CA, the gene that encodes the p110α catalytic subunit of PI3K, only in affected cells. Sequencing of PIK3CA in ten additional individuals with overlapping syndromes identified either the p.His1047Leu alteration or a second cancer-associated alteration, p.His1047Arg, in nine cases. Affected dermal fibroblasts showed enhanced basal and epidermal growth factor (EGF)-stimulated phosphatidylinositol 3,4,5-trisphosphate (PIP(3)) generation and concomitant activation of downstream signaling relative to their unaffected counterparts. Our findings characterize a distinct overgrowth syndrome, biochemically demonstrate activation of PI3K signaling and thereby identify a rational therapeutic target.

Measuring abdominal adipose tissue: comparison of simpler methods with MRI.

OBJECTIVE: This cross-sectional study compares the relationship of visceral and total abdominal adipose tissue (VAT and TAAT) measurements obtained with magnetic resonance imaging (MRI) and a range of 'simpler' techniques suitable for field or bedside use: BMI, waist circumference (WC), bioelectrical impedance (BIA) devices and dual X-ray absorptiometry (DXA). METHOD: 120 participants were recruited, stratified by gender and BMI (20 men and 20 women within each group: lean, overweight and obese). Measurements included height, weight, WC (at midpoint), DXA L2-L4 fat, and BIA (two whole-body and one abdominal device). MRI was used as the reference. RESULTS: MRI data showed that men have more VAT than women, (mean 147 vs. 93 cm(2)) despite less TAAT (362 vs. 405 cm(2)). Correlations of simpler abdominal fat measures showed significantly higher correlations with TAAT than with VAT in men and women. Similarly, trunk and whole-body fat measures were significantly more strongly correlated with TAAT than with VAT. CONCLUSION: None of the simpler techniques show strong correlations with VAT measured by MRI, but WC, abdominal BIA 'visceral fat level' and DXA L2-L4 fat all show similar and strong correlations with TAAT and may be useful in large scale surveys.

Validity of a new abdominal bioelectrical impedance device to measure abdominal and visceral fat: comparison with MRI.

Abdominal fat, and in particular, visceral adipose tissue (VAT), is the critical fat depot associated with metabolic aberrations. At present, VAT can only be accurately measured by computed tomography or magnetic resonance imaging (MRI). This study was designed to compare a new abdominal bioelectrical impedance (BIA) device against total abdominal adipose tissue (TAAT) and VAT area measurements made from an abdominal MRI scan, and to assess its reliability and accuracy. One-hundred twenty participants were recruited, stratified by gender and BMI. Participants had triplicate measures of abdominal fat and waist circumference (WC) with the AB-140 (Tanita, Tokyo, Japan) and WC measurements using a manual tape measure. A single abdominal MRI scan was performed as the reference method. Triplicate measures with the AB-140 showed excellent precision for "visceral fat level," trunk fat %, and WC. AB-140 "visceral fat level" showed significantly stronger correlations with MRI TAAT area than with MRI VAT area (r = 0.94 vs. 0.65 in men and 0.92 vs. 0.64 in women). AB-140 WC showed good correlation with manual WC measurements (r = 0.95 in men and 0.90 in women). AB-140 and manual WCs showed comparable correlations with MRI TAAT area (r = 0.92 and 0.96 in men and 0.88 and 0.88 in women). AB-140 is a simple, quick, and precise technique to measure abdominal fat and WC in healthy adults. It provides a useful proxy for TAAT measured by MRI, comparable to the correlation obtained with manual WC measurements. Neither the AB-140 abdominal fat measures nor WC measurement appear to provide a useful proxy measure of VAT.