Computed Ultrasound Tomography in Echo mode (CUTE) of speed of sound for diagnosis and for aberration correction in pulse-echo sonography

Sound speed as a diagnostic marker for various diseases of human tissue has been of interest for a while. Up to now, mostly transmission ultrasound computed tomography (UCT) was able to detect spatially resolved sound speed, and its promise as a diagnostic tool has been demonstrated. However, UCT is limited to acoustically transparent samples such as the breast. We present a novel technique where spatially resolved detection of sound speed can be achieved using conventional pulse-echo equipment in reflection mode. For this purpose, pulse-echo images are acquired under various transmit beam directions and a two-dimensional map of the sound speed is reconstructed from the changing phase of local echoes using a direct reconstruction method. Phantom results demonstrate that a high spatial resolution (1 mm) and contrast (0.5 % of average sound speed) can be achieved suitable for diagnostic purposes. In comparison to previous reflection-mode based methods, CUTE works also in a situation with only diffuse echoes, and its direct reconstruction algorithm enables real-time application. This makes it suitable as an addition to conventional clinical ultrasound where it has the potential to benefit diagnosis in a multimodal approach. In addition, knowledge of the spatial distribution of sound speed allows full aberration correction and thus improved spatial resolution and contrast of conventional B-mode ultrasound. © (2014) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE). Downloading of the abstract is permitted for personal use only.

Full correction for spatially distributed speed-of-sound in echo ultrasound based on measuring aberration delays via transmit beam steering

Aberrations of the acoustic wave front, caused by spatial variations of the speed-of-sound, are a main limiting factor to the diagnostic power of medical ultrasound imaging. If not accounted for, aberrations result in low resolution and increased side lobe level, over all reducing contrast in deep tissue imaging. Various techniques have been proposed for quantifying aberrations by analysing the arrival time of coherent echoes from so-called guide stars or beacons. In situations where a guide star is missing, aperture-based techniques may give ambiguous results. Moreover, they are conceptually focused on aberrators that can be approximated as a phase screen in front of the probe. We propose a novel technique, where the effect of aberration is detected in the reconstructed image as opposed to the aperture data. The varying local echo phase when changing the transmit beam steering angle directly reflects the varying arrival time of the transmit wave front. This allows sensing the angle-dependent aberration delay in a spatially resolved way, and thus aberration correction for a spatially distributed volume aberrator. In phantoms containing a cylindrical aberrator, we achieved location-independent diffraction-limited resolution as well as accurate display of echo location based on reconstructing the speed-of-sound spatially resolved. First successful volunteer results confirm the clinical potential of the proposed technique.

Line focusing for soft x-ray laser-plasma lasing

A computational study of line-focus generation was done using a self-written ray-tracing code and compared to experimental data. Two line-focusing geometries were compared, i.e., either exploiting the sagittal astigmatism of a tilted spherical mirror or using the spherical aberration of an off-axis- illuminated spherical mirror. Line focusing by means of astigmatism or spherical aberration showed identical results as expected for the equivalence of the two frames of reference. The variation of the incidence angle on the target affects the line-focus length, which affects the amplification length such that as long as the irradiance is above the amplification threshold, it is advantageous to have a longer line focus. The amplification threshold is physically dependent on operating parameters and plasma-column conditions and in the present study addresses four possible cases.

The prognostic significance of cytogenetic aberrations in childhood acute myeloid leukaemia. A study of the Swiss Paediatric Oncology Group (SPOG)

In childhood-onset acute myeloid leukaemia (AML) the clinical value of karyotypic aberrations is now acknowledged, although there is still debate concerning the prognostic significance of some events. To add to this knowledge, cytogenetic analysis was performed on a consecutive series of 84 childhood AML patients diagnosed in Switzerland. A result was obtained for all patients, with 69 (82%) showing a clonal karyotypic aberration. In the remaining 15 (18%), no karyotypic aberration was seen by either conventional or fluorescence in situ hybridisation analyses. The most frequent aberrations observed were t(11q23) (19% of all patients), t(8;21) (12%) and +8 (11%). Except for cytogenetics, no clinical parameter was shown to be significantly associated with outcome. The analysis of individual cytogenetic subgroups demonstrated that aberrations involving chromosome 16q were the strongest predictor of a good prognosis, while +8 and complex karyotypes represented the strongest predictors of a poor prognosis. It was also noteworthy that patients with the rare aberrations of del(11q) (n = 4) and t(16;21)(p11;q22) (n = 3) had a poor outcome. The results support the importance of cytogenetic analysis in childhood AML, but show that further work is required in the classification of the poor prognosis aberrations.

Karyotypic characterization of infant embryonal rhabdomyosarcoma

Despite embryonal rhabdomyosarcoma (eRMS) representing the most frequent form of RMS, the karyotypic characterization of this tumor subtype is still incomplete. We report the karyotypic analysis of two new cases of infant-onset eRMS. Both cases had a hyperdiploid karyotype, including gain of chromosomes 2 and 8. Only one of the cases showed a structural aberration, an unbalanced rearrangement involving 4p. These cases, together with a review of the literature, suggest that a karyotypic subgroup exists in infant eRMS that is defined by hyperdiploidy (<53 chromosomes) and includes gain of chromosomes 2, 8, 11, and 17, with few or no structural aberrations. Hence, this report illustrates that distinct karyotypic subgroups may be found in eRMS, which ultimately may be shown to have prognostic relevance.

The NF-{kappa}B negative regulator TNFAIP3 (A20) is inactivated by somatic mutations and genomic deletions in marginal zone lymphomas

Unique and shared cytogenetic abnormalities have been documented for marginal zone lymphomas (MZLs) arising at different sites. Recently, homozygous deletions of the chromosomal band 6q23, involving the tumor necrosis factor alpha-induced protein 3 (TNFAIP3, A20) gene, a negative regulator of NF-kappaB, were described in ocular adnexal MZL, suggesting a role for A20 as a tumor suppressor in this disease. Here, we investigated inactivation of A20 by DNA mutations or deletions in a panel of extranodal MZL (EMZL), nodal MZL (NMZL), and splenic MZL (SMZL). Inactivating mutations encoding truncated A20 proteins were identified in 6 (19%) of 32 MZLs, including 2 (18%) of 11 EMZLs, 3 (33%) of 9 NMZLs, and 1 (8%) of 12 SMZLs. Two additional unmutated nonsplenic MZLs also showed monoallelic or biallelic A20 deletions by fluorescent in situ hybridization (FISH) and/or SNP-arrays. Thus, A20 inactivation by either somatic mutation and/or deletion represents a common genetic aberration across all MZL subtypes, which may contribute to lymphomagenesis by inducing constitutive NF-kappaB activation.

Juvenile myoclonic epilepsy with photosensitivity in a female with Velocardiofacial syndrome (del(22)(q11.2))--causal relationship or coincidence?

We report on an adolescent female with Velocardiofacial syndrome (del(22)(q11.2)) and an epilepsy phenotype resembling juvenile myoclonic epilepsy (JME). Clinically, the patient has characteristic signs of both disorders. JME has been linked to several chromosomes, but has not been related to 22q11.2 and is rarely observed in other genetic syndromes. We discuss possible explanations for a relationship between the chromosomal aberration and epilepsy as well as the importance of precise delineation of both epilepsy phenotypes and genetic defects in chromosomal disorders.

A practical approach to designing syndromic surveillance systems for livestock and poultry

The field of animal syndromic surveillance (SyS) is growing, with many systems being developed worldwide. Now is an appropriate time to share ideas and lessons learned from early SyS design and implementation. Based on our practical experience in animal health SyS, with additions from the public health and animal health SyS literature, we put forward for discussion a 6-step approach to designing SyS systems for livestock and poultry. The first step is to formalise policy and surveillance goals which are considerate of stakeholder expectations and reflect priority issues (1). Next, it is important to find consensus on national priority diseases and identify current surveillance gaps. The geographic, demographic, and temporal coverage of the system must be carefully assessed (2). A minimum dataset for SyS that includes the essential data to achieve all surveillance objectives while minimizing the amount of data collected should be defined. One can then compile an inventory of the data sources available and evaluate each using the criteria developed (3). A list of syndromes should then be produced for all data sources. Cases can be classified into syndrome classes and the data can be converted into time series (4). Based on the characteristics of the syndrome-time series, the length of historic data available and the type of outbreaks the system must detect, different aberration detection algorithms can be tested (5). Finally, it is essential to develop a minimally acceptable response protocol for each statistical signal produced (6). Important outcomes of this pre-operational phase should be building of a national network of experts and collective action and evaluation plans. While some of the more applied steps (4 and 5) are currently receiving consideration, more emphasis should be put on earlier conceptual steps by decision makers and surveillance developers (1-3).

Influence of Gilbert's syndrome on the formation of ethyl glucuronide.

A drinking experiment with participants suffering from Gilbert's syndrome was performed to study the possible influence of this glucuronidation disorder on the formation of ethyl glucuronide (EtG). Gilbert's syndrome is a rather common and, in most cases, asymptomatic congenital metabolic aberration with a prevalence of about 5 %. It is characterized by a reduction of the enzyme activity of the uridine diphosphate glucuronosyltransferase (UGT) isoform 1A1 up to 80 %. One of the glucuronidation products is EtG, which is formed in the organism following exposure to ethanol. EtG is used as a short-term marker for ethyl alcohol consumption to prove abstinence in various settings. After 2 days of abstinence from ethanol and giving a void urine sample, 30 study participants drank 0.1 L of sparkling wine (9 g ethanol). 3, 6, 12, and 24 h after drinking, urine samples were collected. 3 hours after drinking, an additional blood sample was taken, in which liver enzyme activities, ethanol, hematological parameters, and bilirubin were measured. EtG and ethyl sulfate (EtS), another short-term marker of ethanol consumption, were determined in the urine samples using liquid chromatography-tandem mass spectrometry (LC-MS/MS); creatinine was measured photometrically. In all participants, EtG and EtS were detected in concentrations showing a wide range (EtG: 3 h sample 0.5-18.43 mg/L and 6 h sample 0.67-13.8 mg/L; EtS: 3 h sample 0.87-6.87 mg/L and 6 h sample 0.29-4.48 mg/L). No evidence of impaired EtG formation was found. Thus, EtG seems to be a suitable marker for ethanol consumption even in individuals with Gilbert's syndrome.

Spatial genomic heterogeneity within localized, multifocal prostate cancer

Herein we provide a detailed molecular analysis of the spatial heterogeneity of clinically localized, multifocal prostate cancer to delineate new oncogenes or tumor suppressors. We initially determined the copy number aberration (CNA) profiles of 74 patients with index tumors of Gleason score 7. Of these, 5 patients were subjected to whole-genome sequencing using DNA quantities achievable in diagnostic biopsies, with detailed spatial sampling of 23 distinct tumor regions to assess intraprostatic heterogeneity in focal genomics. Multifocal tumors are highly heterogeneous for single-nucleotide variants (SNVs), CNAs and genomic rearrangements. We identified and validated a new recurrent amplification of MYCL, which is associated with TP53 deletion and unique profiles of DNA damage and transcriptional dysregulation. Moreover, we demonstrate divergent tumor evolution in multifocal cancer and, in some cases, tumors of independent clonal origin. These data represent the first systematic relation of intraprostatic genomic heterogeneity to predicted clinical outcome and inform the development of novel biomarkers that reflect individual prognosis.

Radiographic volume analysis as a novel tool to determine nasopalatine duct cyst dimensions and its association with presenting symptoms and postoperative complications

OBJECTIVES The aims of the study were to use cone beam computed tomography (CBCT) images of nasopalatine duct cysts (NPDC) and to calculate the diameter, surface area, and 3D-volume using a custom-made software program. Furthermore, any associations of dimensions of NPDC with age, gender, presence/absence of maxillary incisors/canines (MI/MC), endodontic treatment of MI/MC, presenting symptoms, and postoperative complications were evaluated. MATERIAL AND METHODS The study comprised 40 patients with a histopathologically confirmed NPDC. On preoperative CBCT scans, curves delineating the cystic borders were drawn in all planes and the widest diameter (in millimeter), surface area (in square millimeter), and volume (in cubic millimeter) were calculated. RESULTS The overall mean cyst diameter was 15 mm (range 7-47 mm), the mean cyst surface area 566 mm(2) (84-4,516 mm(2)), and the mean cyst volume 1,735 mm(3) (65-25,350 mm(3)). For 22 randomly allocated cases, a second measurement resulted in a mean absolute aberration of ±4.2 % for the volume, ±2.8 % for the surface, and ±4.9 % for the diameter. A statistically significant association was found for the CBCT determined cyst measurements and the need for preoperative endodontic treatment to MI/MC and for postoperative complications. CONCLUSION In the hands of a single experienced operator, the novel software exhibited high repeatability for measurements of cyst dimensions. Further studies are needed to assess the application of this tool for dimensional analysis of different jaw cysts and lesions including treatment planning. CLINICAL RELEVANCE Accurate radiographic information of the bone volume lost (osteolysis) due to expansion of a cystic lesion in three dimensions could help in personalized treatment planning.

Shorter telomeres correlate with an increase in the number of uniparental disomies in patients with chronic lymphocytic leukemia.

This study investigated the correlation of the extent of chromosomal aberrations including uniparental disomies (UPDs) by SNP-chip analysis and FISH to telomere length in 46 patients with CLL. CLL harboring high risk aberrations, i.e. deletions of 11q22-23 or 17p13, had significantly shorter telomeres (higher ΔTL) compared to patients with CLL without such abnormalities. Patients with high chromosomal aberration rates had a worse overall survival compared to cases with lower aberration rates. Interestingly, however, an increase was found in the number of UPDs with shorter telomeres. These findings support the idea that telomeres in CLL cells play a role in the overall chromosome stability and could be involved in the occurrence of UPDs.

Investigating the potential of reported cattle mortality data in Switzerland for syndromic surveillance

Systems for the identification and registration of cattle have gradually been receiving attention for use in syndromic surveillance, a relatively recent approach for the early detection of infectious disease outbreaks. Real or near real-time monitoring of deaths or stillbirths reported to these systems offer an opportunity to detect temporal or spatial clusters of increased mortality that could be caused by an infectious disease epidemic. In Switzerland, such data are recorded in the "Tierverkehrsdatenbank" (TVD). To investigate the potential of the Swiss TVD for syndromic surveillance, 3 years of data (2009-2011) were assessed in terms of data quality, including timeliness of reporting and completeness of geographic data. Two time-series consisting of reported on-farm deaths and stillbirths were retrospectively analysed to define and quantify the temporal patterns that result from non-health related factors. Geographic data were almost always present in the TVD data; often at different spatial scales. On-farm deaths were reported to the database by farmers in a timely fashion; stillbirths were less timely. Timeliness and geographic coverage are two important features of disease surveillance systems, highlighting the suitability of the TVD for use in a syndromic surveillance system. Both time series exhibited different temporal patterns that were associated with non-health related factors. To avoid false positive signals, these patterns need to be removed from the data or accounted for in some way before applying aberration detection algorithms in real-time. Evaluating mortality data reported to systems for the identification and registration of cattle is of value for comparing national data systems and as a first step towards a European-wide early detection system for emerging and re-emerging cattle diseases.