MYTHEN CdTe: a new generation state-of-the-art X-ray imaging detector

© 2016 Dr. Stefanie Elbracht-LeongMYTHEN is a single photon counting hybrid strip X-ray detector that has found application in X-ray powder diffraction (XRPD) experiments at synchrotrons worldwide. Originally designed to operate with hole collecting silicon sensors, MYTHEN is suited for detecting X-rays above 5 keV. However many PD beamlines have been designed for energies above 50 keV where silicon sensors have an efficiency of only a few percent. In order to adapt MYTHEN to meet these energies, the absorption efficiency of the sensor must be substantially increased. Cadmium-telluride (CdTe) has an absorption efficiency approximately 30 times that of silicon at 50 keV, and is therefore a very promising replacement sensor material candidate. Furthermore, the large dynamic range of the pre-amplifier of MYTHEN and its capability to process charge carriers of either polarity has enabled the characterization of both electron and hole collecting CdTe sensors. A selection of Schottky and ohmic type CdTe MYTHEN test structures have undergone a series of characterization experiments including bias and settings optimization, energy calibration, count rate capability as well as stability tests of bias and radiation induced polarizations. The performance of those systems will be presented and discussed in this thesis. Both, the radiation and bias induced polarization effects remained manageable. The MYTHEN system combined with CdTe sensors has proven to be reliable and stable despite high stress experiments. When biased over an extended period of time, the results of the studies have demonstrated that overdepletion of the sensors allowed the system to remain functional for a period of time 6 fold longer. During the high radiation studies, a count rate loss as well as a shift in threshold were observed, leading to the conclusion that individual charge carriers are been trapped. When applying a high bias as well as high flux, the detector system remained functional for 30 minutes. It was also demonstrated that a brief power cycle resumed normal performance after the system had shown symptoms of either polarization effect. Overall, the polarization effects observed on MYTHEN CdTe strip detector are temporary and show a slower impact than reported in the literature. Generally, a higher bias improved the stability of the detector

Investigation of current models of care for genetic heart disease in Australia: A national clinical audit

Background: This sub-study of the Australian Genomics Cardiovascular Genetic Disorders Flagship sought to conduct the first nation-wide audit in Australia to establish the current practices across cardiac genetics clinics. Method: An audit of records of patients with a suspected genetic heart disease (cardiomyopathy, primary arrhythmia, autosomal dominant congenital heart disease) who had a cardiac genetics consultation between 1st January 2016 and 31 July 2018 and were offered a diagnostic genetic test. Results: This audit included 536 records at multidisciplinary cardiac genetics clinics from 11 public tertiary hospitals across five Australian states. Most genetic consultations occurred in a clinic setting (90%), followed by inpatient (6%) and Telehealth (4%). Queensland had the highest proportion of Telehealth consultations (9% of state total). Sixty-six percent of patients had a clinical diagnosis of a cardiomyopathy, 28% a primary arrhythmia, and 0.7% congenital heart disease. The reason for diagnosis was most commonly as a result of investigations of symptoms (73%). Most patients were referred by a cardiologist (85%), followed by a general practitioner (9%) and most genetic tests were funded by the state Genetic Health Service (73%). Nationally, 29% of genetic tests identified a pathogenic or likely pathogenic gene variant; 32% of cardiomyopathies, 26% of primary arrhythmia syndromes, and 25% of congenital heart disease. Conclusion: We provide important information describing the current models of care for genetic heart diseases throughout Australia. These baseline data will inform the implementation and impact of whole genome sequencing in the Australian healthcare landscape

A multitiered analysis platform for genome sequencing: Design and initial findings of the Australian Genomics Cardiovascular Disorders Flagship

Purpose: The Australian Genomics Cardiovascular Disorders Flagship was a national multidisciplinary collaboration. It aimed to investigate the feasibility of genome sequencing (GS) and functional genomics to resolve variants of uncertain significance (VUS) in the clinical management of patients and families with cardiomyopathies, primary arrhythmias, and congenital heart disease (CHD). Methods: Between April 2019 and December 2021, 600 probands meeting cardiovascular disorder criteria from 17 cardiology and genetics clinics across Australia were enrolled in the Flagship and underwent GS. The Flagship adopted a tiered approach to GS analysis. Tier 1 analysis assessed genes with established clinical validity for each cardiovascular condition. Tier 2 analysis assessed lesser-evidenced research-based genes. Tier 3 analysis assessed the functional impact of VUS that remained after tier 1 and tier 2 analysis. Results: Overall, a pathogenic or likely pathogenic variant was identified in 41% of participants with a cardiomyopathy, 40% with an arrhythmia syndrome, and 15% with a familial CHD/CHD+Extra Cardiac Anomalies. A VUS outcome ranged from 13% for arrhythmias to 34% for CHD/CHD+Extra Cardiac Anomalies participants. Tier 2 research analysis identified a likely pathogenic/pathogenic variant for a further 15 participants and a VUS for an additional 15 participants. Conclusion: The Flagship successfully facilitated a model of care that harnesses clinical GS and functional genomics for the resolution of VUS in the clinical setting. This valuable data set can be used to inform clinical practice and facilitate research into the future