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.

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.

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.

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.

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.

Mutations in the selenocysteine insertion sequence-binding protein 2 gene lead to a multisystem selenoprotein deficiency disorder in humans.

Selenium, a trace element that is fundamental to human health, is incorporated into some proteins as selenocysteine (Sec), generating a family of selenoproteins. Sec incorporation is mediated by a multiprotein complex that includes Sec insertion sequence-binding protein 2 (SECISBP2; also known as SBP2). Here, we describe subjects with compound heterozygous defects in the SECISBP2 gene. These individuals have reduced synthesis of most of the 25 known human selenoproteins, resulting in a complex phenotype. Azoospermia, with failure of the latter stages of spermatogenesis, was associated with a lack of testis-enriched selenoproteins. An axial muscular dystrophy was also present, with features similar to myopathies caused by mutations in selenoprotein N (SEPN1). Cutaneous deficiencies of antioxidant selenoenzymes, increased cellular ROS, and susceptibility to ultraviolet radiation-induced oxidative damage may mediate the observed photosensitivity. Reduced levels of selenoproteins in peripheral blood cells were associated with impaired T lymphocyte proliferation, abnormal mononuclear cell cytokine secretion, and telomere shortening. Paradoxically, raised ROS in affected subjects was associated with enhanced systemic and cellular insulin sensitivity, similar to findings in mice lacking the antioxidant selenoenzyme glutathione peroxidase 1 (GPx1). Thus, mutation of SECISBP2 is associated with a multisystem disorder with defective biosynthesis of many selenoproteins, highlighting their role in diverse biological processes.

Visceral abdominal obesity--is there an increased prevalence in men presenting with testicular teratoma?

BACKGROUND: There is evidence to suggest a link between the accumulation of visceral abdominal adipose tissue and an increased incidence of prostate, endometrial, breast, and colonic cancer. PURPOSE: To investigate whether an increase in ratio of visceral to subcutaneous abdominal adipose tissue is demonstrated in patients with testicular teratoma. MATERIAL AND METHODS: Following ethical approval, 22 male patients who had undergone staging computed tomography (CT) between 2004 and 2007 for testicular teratoma were identified from our database. Abdominal adipose tissue distribution for these 22 patients was compared with that of 22 control patients, standardized for age, sex, and body mass index. Visceral and subcutaneous adipose tissue volumes were calculated from a single axial CT slice at the level of the umbilicus. A two-sample t test for the difference in volume ratio between the two groups was used. A P value of < 0.05 was considered statistically significant. RESULTS: There was a statistically significant difference in the mean ratio of visceral to subcutaneous volumes between the teratoma patients and controls (P=0.02). The ratio in teratoma patients was 1.56 times greater than seen in control patients. CONCLUSION: Patients with testicular teratoma have a relatively greater proportion of abdominal visceral adipose tissue compared with controls. This is concordant with published literature for other malignancies.

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.

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.

Aortic calcification is associated with aortic stiffness and isolated systolic hypertension in healthy individuals.

Arterial stiffening is an independent predictor of mortality and underlies the development of isolated systolic hypertension (ISH). A number of factors regulate stiffness, but arterial calcification is also likely to be important. We tested the hypotheses that aortic calcification is associated with aortic stiffness in healthy individuals and that patients with ISH exhibit exaggerated aortic calcification compared with controls. A total of 193 healthy, medication-free subjects (mean age+/-SD: 66+/-8 years) were recruited from the community, together with 15 patients with resistant ISH. Aortic pulse wave velocity (PWV) was measured noninvasively, and aortic calcium content was quantified from high-resolution, thoraco-lumbar computed tomography images using a volume scoring method. In healthy volunteers, calcification was positively and significantly associated with aortic PWV (r=0.6; P<0.0001) but was not related to augmentation index or brachial PWV. Calcification was significantly higher in treatment-resistant and healthy subjects with ISH compared with controls (mean [interquartile range]: 1.92 [1.14 to 3.66], 0.84 [0.35 to 1.75], and 0.19 [0.1 to 0.78] cm3, respectively; P<0.0001 for both). In a multiple regression model, aortic calcium was independently associated with aortic PWV along with age, mean arterial pressure, heart rate, and estimated glomerular filtration rate (R(2)=0.51; P<0.0001). Only age, calcium phosphate product, and aortic PWV were independently associated with calcification. These data suggest that calcification may be important in the process of aortic stiffening and the development of ISH. Calcification may underlie treatment resistance in ISH, and anticalcification strategies may present a novel therapy.

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.