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The rising cancer incidence and mortality in sub-Saharan Africa (SSA) warrants an increased focus on adopting or developing approaches that can significantly increase access to treatment in the region. One such approach recommended by the recent Lancet Oncology Commission for sub-Saharan Africa is hypofractionated radiotherapy (HFRT), which can substantially increase access to radiotherapy by reducing the overall duration of time (in days) each person spends being treated. Here we highlight challenges in adopting such an approach identified during the implementation of the HypoAfrica clinical trial. The HypoAfrica clinical trial is a longitudinal, multicentre study exploring the feasibility of applying HFRT for prostate cancer in SSA. This study has presented an opportunity for a pragmatic assessment of potential barriers and facilitators to adopting HFRT. Our results highlight three key challenges: quality assurance, study harmonisation and machine maintenance. We describe solutions employed to resolve these challenges and opportunities for longer term solutions that can facilitate scaling-up use of HFRT in SSA in clinical care and multicentre clinical trials. This report provides a valuable reference for the utilisation of radiotherapy approaches that increase access to treatment and the conduct of high-quality large-scale/multi-centre clinical trials involving radiotherapy.

Objective. Deep Learning models are often susceptible to failures after deployment. Knowing when your model is producing inadequate predictions is crucial. In this work, we investigate the utility of Monte Carlo (MC) dropout and the efficacy of the proposed uncertainty metric (UM) for flagging of unacceptable pectoral muscle segmentations in mammograms. Approach. Segmentation of pectoral muscle was performed with modified ResNet18 convolutional neural network. MC dropout layers were kept unlocked at inference time. For each mammogram, 50 pectoral muscle segmentations were generated. The mean was used to produce the final segmentation and the standard deviation was applied for the estimation of uncertainty. From each pectoral muscle uncertainty map, the overall UM was calculated. To validate the UM, a correlation between the dice similarity coefficient (DSC) and UM was used. The UM was first validated in a training set (200 mammograms) and finally tested in an independent dataset (300 mammograms). ROC-AUC analysis was performed to test the discriminatory power of the proposed UM for flagging unacceptable segmentations. Main results. The introduction of dropout layers in the model improved segmentation performance (DSC = 0.95 ± 0.07 versus DSC = 0.93 ± 0.10). Strong anti-correlation (r = −0.76, p < 0.001) between the proposed UM and DSC was observed. A high AUC of 0.98 (97% specificity at 100% sensitivity) was obtained for the discrimination of unacceptable segmentations. Qualitative inspection by the radiologist revealed that images with high UM are difficult to segment. Significance. The use of MC dropout at inference time in combination with the proposed UM enables flagging of unacceptable pectoral muscle segmentations from mammograms with excellent discriminatory power.

The evaluation of treatment response remains a challenge in glioma cases because the neuro oncological therapy can lead to the development of treatment-related changes (TRC) that mimic true progression (TP). Positron emission tomography (PET) using O-(2-[18F] fluoroethyl-)-L-tyrosine (18F-FET) has been shown to be a useful tool for detecting TRC and TP. We assessed the diagnostic performance of different 18F-FET PET segmentation approaches and different imaging biomarkers for differentiation between late TRC and TP in glioma patients. Isocitrate dehydrogenase (IDH) status was evaluated as a predictor of disease outcome. In our study, the proportion of TRC in IDH wild type (IDHwt) and IDH mutant (IDHm) subgroups was without significant difference. We found that the diagnostic value of static and dynamic biomarkers of 18F-FET PET for discrimination between TRC and TP depends on the IDH mutation status of the tumor. Dynamic 18F-FET PET acquisition proved helpful in the IDH wild type (IDHwt) subgroup, as opposed to the IDH mutant (IDHm) subgroup, providing an early indication to discontinue dynamic imaging in the IDHm subgroup.

Background Immune checkpoint inhibitors have changed the paradigm of cancer treatment; however, non-invasive biomarkers of response are still needed to identify candidates for non-responders. We aimed to investigate whether immunotherapy [18F]FDG PET radiomics signature (iRADIOMICS) predicts response of metastatic non-small-cell lung cancer (NSCLC) patients to pembrolizumab better than the current clinical standards. Patients and methods Thirty patients receiving pembrolizumab were scanned with [18F]FDG PET/CT at baseline, month 1 and 4. Associations of six robust primary tumour radiomics features with overall survival were analysed with Mann-Whitney U-test (MWU), Cox proportional hazards regression analysis, and ROC curve analysis. iRADIOMICS was constructed using univariate and multivariate logistic models of the most promising feature(s). Its predictive power was compared to PD-L1 tumour proportion score (TPS) and iRECIST using ROC curve analysis. Prediction accuracies were assessed with 5-fold cross validation. Results The most predictive were baseline radiomics features, e.g. Small Run Emphasis (MWU, p = 0.001; hazard ratio = 0.46, p = 0.007; AUC = 0.85 (95% CI 0.69–1.00)). Multivariate iRADIOMICS was found superior to the current standards in terms of predictive power and timewise with the following AUC (95% CI) and accuracy (standard deviation): iRADIOMICS (baseline), 0.90 (0.78–1.00), 78% (18%); PD-L1 TPS (baseline), 0.60 (0.37–0.83), 53% (18%); iRECIST (month 1), 0.79 (0.62–0.95), 76% (16%); iRECIST (month 4), 0.86 (0.72–1.00), 76% (17%). Conclusions Multivariate iRADIOMICS was identified as a promising imaging biomarker, which could improve management of metastatic NSCLC patients treated with pembrolizumab. The predicted non-responders could be offered other treatment options to improve their overall survival.

ispartof: MEDICAL IMAGING 2022: PHYSICS OF MEDICAL IMAGING vol:12031 ispartof: Conference on Medical Imaging - Physics of Medical Imaging location:ELECTR NETWORK date:20 Feb - 27 Mar 2022 status: published

Differentiation between neurodegenerative parkinsonisms, whose early clinical presentation is similar, may be improved with metabolic brain imaging. In this study we applied a specific network analysis to 2-[20 MSA-P patients, 20 PSP patients and 20 healthy controls (HC) underwent 2-[MSARP was characterized by hypometabolism in cerebellum and putamen, and PSPRP by hypometabolism in medial prefrontal cortices, nucleus caudatus, frontal cortices and mesencephalon. Patterns' expression discriminated between MSA/PSP patients and HCs as well as between different parkinsonian cohorts (p 0.001). Both patterns were sensitive and specific (AUC for MSARP/PSPRP: 0.96/0.99). Heat-map analysis showed differences within MSA/PSP subjects and HCs consistent with clinical presentation.Replication and validation of MSARP and PSPRP confirms robustness of these metabolic biomarkers and supports its application in clinical and research practice. Heat-map analysis gives us an insight into the contribution of various pattern's regions to patterns' expression in individual subjects, which improves our insight into the heterogeneity of studied syndromes.

To assist ongoing investigations of the limits of the tradeoff between spatial resolution and noise in PET imaging, several PET instruments based on silicon-pad detectors have been developed. The latest is a segment of a dual-ring device to demonstrate that excellent reconstructed image resolution can be achieved with a scanner that uses highresolution detectors placed close to the object of interest or surrounding a small field-of-view in combination with detectors having modest resolution at larger radius. The outer ring of our demonstrator comprises conventional BGO block detectors scavenged from a clinical PET scanner and located at a 500 mm radius around a 50 mm diameter field-of-view. The inner detector–in contrast to the high-Z scintillator typically used in PET–is based on silicon-pad detectors located at 70 mm nominal radius. Each silicon detector has 512 1.4 mm x 1.4 mm x 1 mm detector elements in a 16 x 32 array and is read out using VATA GP7 ASICs (Gamma Medica-Ideas, Northridge, CA). Even though virtually all interactions of 511 keV annihilation photons in silicon are Compton-scatter, both high spatial resolution and reasonable sensitivity appears possible. The system has demonstrated resolution of ∼ 0.7 mm FWHM with Na-22 for coincidences having the highest intrinsic resolution (silicon-silicon) and 5–6 mm FWHM for the lowest resolution BGO-BGO coincidences. Spatial resolution for images reconstructed from the mixed silicon-BGO coincidences is ∼1.5 mm FWHM demonstrating the “magnifying-glass” concept.

Introduction Potential changes in patient anatomy during proton radiotherapy may lead to a deviation of the delivered dose. A dose estimate can be computed through a deformable image registration (DIR) driven dose accumulation. The present study evaluates the accumulated dose uncertainties in a patient subject to an inadvertent breathing associated motion. Materials and methods A virtual lung tumour was inserted into a pair of single participant landmark annotated computed tomography images depicting opposite breathing phases, with the deep inspiration breath-hold the planning reference and the exhale the off-reference geometry. A novel Monte Carlo N-Particle, Version 6 (MCNP6) dose engine was developed, validated and used in treatment plan optimization. Three DIR methods were compared and used to transfer the exhale simulated dose to the reference geometry. Dose conformity and homogeneity measures from International Committee on Radioactivity Units and Measurements (ICRU) reports 78 and 83 were evaluated on simulated dose distributions registered with different DIR algorithms. Results The MCNP6 dose engine handled patient-like geometries in reasonable dose calculation times. All registration methods were able to align image associated landmarks to distances, comparable to voxel sizes. A moderate deterioration of ICRU measures was encountered in comparing doses in on and off-reference anatomy. There were statistically significant DIR driven differences in ICRU measures, particularly a 10% difference in the relative D98% for planning tumour volume and in the 3 mm/3% gamma passing rate. Conclusions T he dose accumulation over two anatomies resulted in a DIR driven uncertainty, important in reporting the associated ICRU measures for quality assurance.

ObjectivesThis study investigated the performance and robustness of radiomics in predicting COVID-19 severity in a large public cohort.MethodsA public dataset of 1110 COVID-19 patients (1 CT/patient) was used. Using CTs and clinical data, each patient was classified into mild, moderate, and severe by two observers: (1) dataset provider and (2) a board-certified radiologist. For each CT, 107 radiomic features were extracted. The dataset was randomly divided into a training (60%) and holdout validation (40%) set. During training, features were selected and combined into a logistic regression model for predicting severe cases from mild and moderate cases. The models were trained and validated on the classifications by both observers. AUC quantified the predictive power of models. To determine model robustness, the trained models was cross-validated on the inter-observer’s classifications.ResultsA single feature alone was sufficient to predict mild from severe COVID-19 with and (p<< 0.01). The most predictive features were the distribution of small size-zones (GLSZM-SmallAreaEmphasis) for provider’s classification and linear dependency of neighboring voxels (GLCM-Correlation) for radiologist’s classification. Cross-validation showed that both . In predicting moderate from severe COVID-19, first-order-Median alone had sufficient predictive power of . For radiologist’s classification, the predictive power of the model increased to as the number of features grew from 1 to 5. Cross-validation yielded and .ConclusionsRadiomics significantly predicted different levels of COVID-19 severity. The prediction was moderately sensitive to inter-observer classifications, and thus need to be used with caution.Key pointsInterpretable radiomic features can predict different levels of COVID-19 severityMachine Learning-based radiomic models were moderately sensitive to inter-observer classifications, and thus need to be used with caution

Primer samohvale in karierizma v kriznih časih slovenskega zgodovinopisja

Conventional PET systems can be augmented with additional detectors placed in close proximity of the region of interest. We developed a high resolution PET insert module to evaluate the added benefit of such a combination. The insert module consists of two back-to-back 1 mm thick silicon sensors, each segmented into 1040 1 mm(2) pads arranged in a 40 by 26 array. A set of 16 VATAGP7.1 ASICs and a custom assembled data acquisition board were used to read out the signal from the insert module. Data were acquired in slice (2D) geometry with a Jaszczak phantom (rod diameters of 1.2–4.8 mm) filled with (18)F-FDG and the images were reconstructed with ML-EM method. Both data with full and limited angular coverage from the insert module were considered and three types of coincidence events were combined. The ratio of high-resolution data that substantially improves quality of the reconstructed image for the region near the surface of the insert module was estimated to be about 4%. Results from our previous studies suggest that such ratio could be achieved at a moderate technological expense by using an equivalent of two insert modules (an effective sensor thickness of 4 mm).

In a dual PET ring detector, a high resolution detector ring is placed within a standard PET ring. For the outer ring detector with a spatial resolution significantly worse than the resolution of the inner ring, it has been shown that the combined detector performs significantly better than a ring only system. To test performance in a system with a high resolution ring detectors, a LYSO PET module was built with total size equal to the standard size of PET detector modules, and a resolution of 1.5 mm FWHM. This paper reports characterization and calibration of the LYSO PET module and results of the preliminary PET imaging test.

The probe arrangement in positron emission tomography (PET) is a combination of a high resolution detector (probe) placed within a whole body PET scanner. An additional subset of high-resolution data is recorded that contains events where one of the annihilation photon pair interacted in the high resolution detector. A study was designed to evaluate impact of probe geometry and efficiency on the quality of obtained image. The performance was predicted by estimating mean and variance of efficient estimators such as MLEM based on imaging matrix evaluated at particular probe geometry. Results were compared to data measured at a high-resolution PET probe prototype constructed at University of Michigan. The prototype consists of two arcs of standard PET detector elements at 50 cm radius combined with silicon sensors segmented into 1 mm3 at 5.7 cm radius. A high-resolution Derenzo phantom filled with 18F-flourodeoxyglucose was rotated during a scan. Limited angle probe geometry was simulated by selection of a subset of phantom angular views. Data reconstruction was matched to algorithms evaluated in theoretical predictions. Two parameters, contrast recovery coefficient (CRC) and signal to noise ratio (SNR) were compared to predicted values. The data shows a 50 % increase in CRC and SNR at an event ratio of 10 % where improvement is maximized for a subset of angular positions. Splitting high-resolution data to two perpendicular angular positions improves CRC and SNR.

A high-resolution PET system, which incorporates a silicon detector probe into a conventional PET scanner, has been proposed to obtain increased image quality in a limited region of interest. Detailed simulation studies have previously shown that the additional probe information improves the spatial resolution of the reconstructed image and increases lesion detectability, with no cost to other image quality measures. The current study expands on the previous work by using a laboratory prototype of the silicon PET-probe system to examine the resolution improvement in an experimental setting. Two different versions of the probe prototype were assessed, both consisting of a back-to-back pair of 1-mm thick silicon pad detectors, one arranged in 32 × 16 arrays of 1.4 mm × 1.4 mm pixels and the other in 40 × 26 arrays of 1.0 mm × 1.0 mm pixels. Each detector was read out by a set of VATAGP7 ASICs and a custom-designed data acquisition board which allowed trigger and data interfacing with the PET scanner, itself consisting of BGO block detectors segmented into 8 × 6 arrays of 6 mm × 12 mm × 30 mm crystals. Limited-angle probe data was acquired from a group of Na-22 point-like sources in order to observe the maximum resolution achievable using the probe system. Data from a Derenzo-like resolution phantom was acquired, then scaled to obtain similar statistical quality as that of previous simulation studies. In this case, images were reconstructed using measurements of the PET ring alone and with the inclusion of the probe data. Images of the Na-22 source demonstrated a resolution of 1.5 mm FWHM in the probe data, the PET ring resolution being approximately 6 mm. Profiles taken through the image of the Derenzo-like phantom showed a clear increase in spatial resolution. Improvements in peak-to-valley ratios of 50% and 38%, in the 4.8 mm and 4.0 mm phantom features respectively, were observed, while previously unresolvable 3.2 mm features were brought to light by the addition of the probe. These results support the possibility of improving the image resolution of a clinical PET scanner using the silicon PET-probe.

A system for in-vivo tracking of 192Ir source during high dose rate or pulsed dose rate brachytherapy treatment was built using 1 mm thick silicon pad detectors as image sensors and knife-edge lead pinholes as collimators. With source self-images obtained from a dual-pinhole system, location of the source could be reconstructed in three dimensions in real time. The system was tested with 192Ir clinical source (kerma rate in air at 1 m 2.38 Gy/h) in air and plexi-glass phantom. The locations of the source were tracked from a distance of 40 cm in a field of view of 20 × 20 × 20 cm3. Reconstruction precision, defined as the average distance between true and reconstructed source positions, with data collected in less than 1 s with 22 GBq 192Ir source was about 5 mm. The reconstruction precision was in our case mainly limited by imperfect alignment of detectors and pinholes. With perfect alignment the statistical error would allow precision of about 1 mm which could further be improved with larger detector placed at larger distance from the pinhole. However already the modest precision of few millimeters is sufficient for in-vivo detection of larger deviations from planned treatment caused by various misadministrations or malfunctioning of the brachytherapy treatment apparatus. Usage of silicon detectors offers a possibility for building a compact device which could be used as an independent online quality assurance system. In this paper details about sensors, readout system and reconstruction algorithm are described. Results from measurements with clinical source are presented.

PET scanners with high spatial resolution offer a great potential in improving diagnosis, therapy monitoring and treatment validation for several severe diseases. One way to improve resolution of a PET scanner is to extend a conventional PET ring with a small probe with excellent spatial resolution. The probe is intended to be placed close to the area of interest. The coincidences of interactions within the probe and the external ring provide a subset of data which combined with data from external ring, greatly improve resolution in the area viewed by the probe. Our collaboration is developing a prototype of a PET probe, composed of high-resolution silicon pad detectors. The detectors are 1 mm thick, measuring 40 by 26 mm2, and several such sensors are envisaged to either compensate for low stopping power of silicon or increase the area covered by the probe. The sensors are segmented into 1 mm3 cubic voxels, giving 1040 readout pads per sensor. A module is composed of two sensors placed in a back-to-back configuration, allowing for stacking fraction of up to 70% within a module. The pads are coupled to a set of 16 ASICs (VaTaGP7.1 by IDEAS) per module and read out through a custom designed data acquisition board, allowing for trigger and data interfacing with the external ring. This paper presents an overview of probe requirements and expected performance parameters. It will focus on the characteristics of the silicon modules and their impact on overall probe performance, including spatial resolution, energy resolution and timing resolution. We will show that 1 mm3 voxels will significantly extend the spatial resolution of conventional PET rings, and that broadening of timing resolution related to varying depth of photon interactions can be compensated to match the timing resolution of the external ring. The initial test results of the probe will also be presented.

Simulation indicates that PET image could be improved by upgrading a conventional ring with a probe placed close to the imaged object. In this paper, timing issues related to a PET probe using high-resistivity silicon as a detector material are addressed. The final probe will consist of several (four to eight) 1-mm thick layers of silicon detectors, segmented into 1 x 1 mm(2) pads, each pad equivalent to an independent p + nn+ diode. A proper matching of events in silicon with events of the external ring can be achieved with a good timing resolution. To estimate the timing performance, measurements were performed on a simplified model probe, consisting of a single 1-mm thick detector with 256 square pads (1.4 mm side), coupled with two VATAGP7s, application-specific integrated circuits. The detector material and electronics are the same that will be used for the final probe. The model was exposed to 511 keV annihilation photons from an (22)Na source, and a scintillator (LYSO)-PMT assembly was used as a timing reference. Results were compared with the simulation, consisting of four parts: (i) GEANT4 implemented realistic tracking of electrons excited by annihilation photon interactions in silicon, (ii) calculation of propagation of secondary ionisation (electron-hole pairs) in the sensor, (iii) estimation of the shape of the current pulse induced on surface electrodes and (iv) simulation of the first electronics stage. A very good agreement between the simulation and the measurements were found. Both indicate reliable performance of the final probe at timing windows down to 20 ns.

A first prostate probe prototype based on the Compton imaging technique has been developed, with a scatter detector composed of a stack of five thick silicon pad detectors, and a scintillator as absorption detector. The silicon sensors are 4 cm times 1 cm, 1 mm thick, with 1.4 mm times 1.4 mm pad dimensions. The scatter detector performance has been optimized, and an energy resolution about 1.4 keV FWHM is obtained. The absorption detector consists of three Nal(Tl) scintillators that are placed around the scatter detector. A spatial resolution of 5 mm FWHM has been measured reconstructing an image of a point-like 133 Ba source placed at 11 cm distance from the scatter detector. Additional studies show the improvement of the detector resolution with increasing incident photon energy and relative distance from the scatter to the absorption detector. Simulations have also been performed for a complete understanding of the data, and to predict the expected resolution at near field operation of the device. The prototype construction is the first step in the development of a Compton probe for prostate imaging.

A very high resolution positron emission tomography (PET) scanner for small animal imaging based on the idea of inserting a ring of high-granularity solid-state detectors into a conventional PET scanner is under investigation. A particularly interesting configuration of this concept, which takes the form of a degenerate Compton camera, is shown capable of providing sub-millimeter resolution with good sensitivity. We present a Compton PET system and estimate its performance using a proof-of-concept prototype. A prototype single-slice imaging instrument was constructed with two silicon detectors 1 mm thick, each having 512 1.4 mm x 1.4 mm pads arranged in a 32 x 16 array. The silicon detectors were located edgewise on opposite sides and flanked by two non-position sensitive BGO detectors. The scanner performance was measured for its sensitivity, energy, timing, spatial resolution and resolution uniformity. Using the experimental scanner, energy resolution for the silicon detectors is 1%. However, system energy resolution is dominated by the 23% FWHM BGO resolution. Timing resolution for silicon is 82.1 ns FWHM due to time-walk in trigger devices. Using the scattered photons, time resolution between the BGO detectors is 19.4 ns FWHM. Image resolution of 980 microm FWHM at the center of the field-of-view (FOV) is obtained from a 1D profile of a 0.254 mm diameter (18)F line source image reconstructed using the conventional 2D filtered back-projection (FBP). The 0.4 mm gap between two line sources is resolved in the image reconstructed with both FBP and the maximum likelihood expectation maximization (ML-EM) algorithm. The experimental instrument demonstrates sub-millimeter resolution. A prototype having sensitivity high enough for initial small animal images can be used for in vivo studies of small animal models of metabolism, molecular mechanism and the development of new radiotracers.

A prostate probe based on the Compton imaging technique can outperform the methods currently employed for prostate imaging, improving early tumour detection, determination of its extent and follow-up of the response to treatment. Although nuclear imaging techniques have proven extremely valuable for this task in a wide variety of non-urologic cancers, present instrumentation is not adequate for prostate imaging. Compton imaging overcomes the resolution–efficiency tradeoff imposed by mechanical collimators, allowing both to improve simultaneously. A first Compton probe prototype has been developed, employing thick silicon sensors as scatter detectors, and its performance has been optimized. A series of measurements have been performed with 57 Co and 133 Ba sources. The results confirm the correct functioning of the prototype and the improvement of the spatial resolution with photon energy, low scattering angles and distance from the first to the second detector.

Silicon based devices can extend PET–MR and SPECT–MR imaging to applications, where their advantages in performance outweigh benefits of high statistical counts. Silicon is in many ways an excellent detector material with numerous advantages, among others: excellent energy and spatial resolution, mature processing technology, large signal to noise ratio, relatively low price, availability, versatility and malleability. The signal in silicon is also immune to effects of magnetic field at the level normally used in MR devices. Tests in fields up to 7 T were performed in a study to determine effects of magnetic field on positron range in a silicon PET device. The curvature of positron tracks in direction perpendicular to the field's orientation shortens the distance between emission and annihilation point of the positron. The effect can be fully appreciated for a rotation of the sample for a fixed field direction, compressing range in all dimensions. A popular Ga-68 source was used showing a factor of 2 improvement in image noise compared to zero field operation. There was also a little increase in noise as the reconstructed resolution varied between 2.5 and 1.5 mm. A speculative applications can be recognized in both emission modalities, SPECT and PET. Compton camera is a subspecies of SPECT, where a silicon based scatter as a MR compatible part could inserted into the MR bore and the secondary detector could operate in less constrained environment away from the magnet. Introducing a Compton camera also relaxes requirements of the radiotracers used, extending the range of conceivable photon energies beyond 140.5 keV of the Tc-99m. In PET, one could exploit the compressed sub-millimeter range of positrons in the magnetic field. To exploit the advantage, detectors with spatial resolution commensurate to the effect must be used with silicon being an excellent candidate. Measurements performed outside of the MR achieving spatial resolution below 1 mm are reported.

The ability to diagnose early prostate cancer has outpaced imaging methods for accurate localization and staging of the disease. A precise determination of the extent of local disease is difficult and, unfortunately, present imaging instrumentation employing radiotracer techniques (PET, SPECT, planar scintigraphy) is limited in its ability to provide detailed information when imaging the prostate due to modest spatial resolution, often poor counting efficiency, and photon attenuation. The innovation in the work described here is the use of a silicon prostate probe based on the principle of the Compton scatter camera. Simulation studies show that the endorectal prostate probe will enhance the spatial resolution by a factor 4–5 and, simultaneously, provide a gain in efficiency of a factor 16–40 over conventional nuclear medicine cameras. The ongoing tasks are focused on the design optimization of a Compton probe prototype.

Applications in nuclear medicine and bio-medical engineering may profit using a Compton camera for imaging distributions of radio-isotope labelled tracers in organs and tissues. These applications require detection of photons using thick position-sensitive silicon sensors with the highest possible energy and good spatial resolution. In this paper, research and development on silicon pad sensors and associated readout electronics for a Compton camera are presented. First results with low-noise, self-triggering VATAGP ASIC's are reported. The measured energy resolution was 1.1 keV FWHM at room temperature for the 241 Am photo-peak at 59.5 keV .

Immediately after the introduction of the King Aleksandar Karađorđević's dictatorship and the censorship became more severe. The press was supposed to subordinate its writing to the efforts of the government or at least avoid mentioning anything that was in contrast with these efforts. Through the press the state wanted to exert an all‑encompassing control over the thinking, political viewpoints, as well as emotions of the people. The author argues on the censorship measures in Styria after the publication of Korošec's Slovenian declaration in 1932.

In the scope of construction of a PET apparatus based on detection of Compton scattering in silicon (Compton camera), the timing properties of 1-mm-thick silicon pad and double-sided microstrip, detectors are studied. Timing in pad detectors is also investigated for 140.5 keV /sup 99m/Tc and 364.5 keV /sup 131/I gamma rays in view of a SPECT application. Compton scattering and energy loss of the Compton electron in the silicon detector are simulated using the GEANT package. The electric field in the detector is calculated numerically for a fully depleted detector in the abrupt junction approximation, taking into account the geometry and varying the reverse voltage. Signal formation is studied using Ramo's theorem and pulse shaping properties of the trigger circuit. A time-walk cut is seen to be directly corresponding to a deposited-energy cut. At 10 keV threshold in 1-mm-thick detectors, 10 ns timing windows are shown to reject a significant portion of events, degrading efficiency or limiting the angular range in a prohibitive way. More involved techniques are therefore suggested, either in the electronics circuit or in later stages of the trigger.

A system for in vivo tracking of 1 Ci 192Ir source during brachytherapy treatment has been built using high resistivity silicon pad detectors as image sensors and knife-edge lead pinholes as collimators. The sensors consist of 256 pads arranged in 32 ×8 grid with pad size 1.4 × 1.4 mm 2 and 1 mm thickness. The sensors have two metal layers, enabling connection of readout electronics (VATAGP3_1 chips) at the edge of the detector. With source self-images obtained from a dual-pinhole system, location of the source can be reconstructed in three dimensions in real time, allowing on-line detection of deviations from planned treatment. The system was tested with 1 Ci 192Ir clinical source in air and plexi-glass phantom. The movements of the source could be tracked in a field of view of approximately 20 × 20 × 20 cm 3 with absolute precision of about 5 mm. Positions of the source, relative to the first measured source position, could be mapped with precision of around 3 mm.

This chapter will describe the development of a PET probe based on solid-state detectors. The PET probe concept combines the high spatial resolution of dedicated PET imaging devices with the large field of view of the standard PET scanners. This is achieved by placing an additional movable detector within the standard PET ring and combining standard events with those captured by the probe. The probe must exhibit excellent spatial resolution and be of compact, sturdy design, making solid-state detectors a compelling choice over scintillator-based materials. Although silicon may not be perfectly suited in terms of stopping power and timing resolution, its other characteristics make it a compelling choice for the probe construction. This chapter will give an overview on probe construction, characterization, and performance as well as outline the limiting aspects of the described approach.

Imaging in nuclear medicine has become an established part of standard medical practice for recognition and treatment of a wide variety of medical disorders. This chapter gives a compact overview of the physics that governs such imaging algorithms.

Positron emission tomography (PET) is a widely used technique in medical imaging and in studying small animal models of human disease. In the conventional approach, the 511 keV annihilation photons emitted from a patient or small animal are detected by a ring of scintillators such as LYSO read out by arrays of photodetectors. Although this has been a successful in achieving ~5mm FWHM spatial resolution in human studies and ~1mm resolution in dedicated small animal instruments, there is interest in significantly improving these figures. Silicon, although its stopping power is modest for 511 keV photons, offers a number of potential advantages over more conventional approaches. Foremost is its high spatial resolution in 3D: our past studies show that there is little diffculty in localizing 511 keV photon interactions to ~0.3mm. Since spatial resolution and reconstructed image noise trade off in a highly non-linear manner that depends on the PET instrument response, if high spatial resolution is the goal, silicon may outperform standard PET detectors even though it has lower sensitivity to 511 keV photons. To evaluate silicon in a variety of PET “magnifying glass” configurations, an instrument has been constructed that consists of an outer partial-ring of PET scintillation detectors into which various arrangements of silicon detectors can be inserted to emulate dual-ring or imaging probe geometries. Recent results have demonstrated 0.7 mm FWHM resolution using pad detectors having 16×32 arrays of 1.4mm square pads and setups have shown promising results in both small animal and PET imaging probe configurations. Although many challenges remain, silicon has potential to become the PET detector of choice when spatial resolution is the primary consideration.

We have developed a data acquisition system for the parallel read-out of silicon pixel detector modules. The front-end electronics of the system is based on the VATAGP7, a Gamma Medica - Ideas application specific integrated circuit (ASIC). The acquisition board (MADDAQ) has an FPGA chip that controls the ASIC configuration and the readout process. Collected data is stored into internal memory and sent to a PC through an Ethernet connection. Several MADDAQ boards can work together independently or in coincidence mode. The system has the option to be synchronized with another setup like in a conventional PET scanner. The full characterization of the system is presented.

We have constructed an enhanced PET scanner from a 1 mm thick silicon detectors as the inner detectors combined with a partial BGO ring. The inner detector trigger is provided by a leading edge discriminator on a CR-RC shaped signal induced by annihilation photon interactions. A shaping time of 150 ns implies a time-walk of similar duration, requiring comparably long hardware coincidence timing windows. The system was set to a planar mode and tested using a Jaszczak phantom with, among others, 1.6 mm diameter holes which match systematic resolution of the mixed mode silicon-BGO events.

The use of ionizing radiation in medical diagnostics became widespread after the dawn of X-ray imaging in the beginning of the past century. The radiation used at present is variable, as are the techniques for its detection. Here, we describe the imaging modalities that use ionizing radiation, basic principles of interaction to which the radiation used is subjected, and statistical and electronic treatment of the measurements.

Madeira project aims to significantly improve three-dimensional (3D) nuclear medicine imaging technologies via a compact photon-sensitive probe interfaced to an external conventional PET ring and placed close to the region of interest. The probe consists of several modules densely packed. Each module is made of two high-resistivity silicon detectors of 1 mm thickness and 1040 square pixels of 1 mm2. The detectors are placed back-to-back at a distance of 0.8 mm. The pads are read out with the VATAGP7 chip, a Gamma Medica — Ideas designed application specific integrated circuit (ASIC). A FPGA based DAQ system has been designed and developed at IFIC-Valencia to read out the probe. The system consists of several DAQ boards working in parallel which control the acquisition process. The DAQ board has trigger and coincidence capabilities to be used in coincidence with a conventional PET scanner. This work describes the characteristics of the system and its architecture, and also the future activities.

Detection and spectroscopic tests of three self-triggered silicon detection modules constructed using Tape Automated Bonding and micro-cable technologies and equipped by VATA read-out chips are presented and compared. Results of these tests are demonstrated using hit maps and pulse-height spectra induced by 133Ba, 241Am, and 57Co radioactive sources of X- and gamma rays. We have observed significant improvement in measurement of hit maps in the cases of first and second detector modules. The hit maps of the first detector module have proven that some problems occur in addressing certain VATA chip channels. Whereas, the hit maps of the second detector module is correct. On the other side, spectroscopic resolution given by the Full Width at Half Maximum (FWHM) of the first detection module is below 2 keV which is compatible with measurements on wire bonded modules. The FWHM of the second module is approximately two times worse.

PET probes are showing a lot of promise in extending performance of the conventional PET ring. The underlying idea is to supplement basic PET data with information collected in the finely segmented probe placed close to the region of interest. The benefit is two fold: a) data collected near the object are less prone to errors related to scattering and acolinearity and b) the object itself is magnified in the proximity focus. The principle would be beneficial to clinical applications where spatial resolution below the current limit is required in a narrow field of view. The probe should therefore have excellent spatial resolution, should be compact and robust and should be able to handle large count rates of the clinical environments. Based on those we decided to explore devices with high-resistivity silicon as the sensitive material. They provide high spatial resolution, are compact and robust, and can handle the foreseen rates. We constructed a prototype, based on 1 mm thick silicon wafers, cut into 40 by 26 mm2 detectors further segmented into 1 × 1 mm2 square pads, effectively providing 1 mm3 sensitive voxels. For a module, two such detectors were placed in a back-to-back arrangement, providing filling factor in excess of 70 %. Stacking multiple modules is foreseen to compensate for low stopping power of silicon. The sensors are read out by 128 channel VATAGP7, GM-Ideas sourced application sensitive integrated circuit. Each module requires 16 chips, placed on 4 custom made PCB boards (hybrids) which are read independently. The modules were characterized and will be placed in a test PET ring. A simple point sources and phantoms will be imaged to confirm the predicted benefits.

This paper reports the characterization of a detector module, the building block to be used for the MADEIRA PET probe prototype. The prototype will be used in synchronization with a conventional PET ring, amplifying the basic image with a subset of events with high spatial resolution. For image improvement, the crucial parameters are the spatial and timing resolution of the probe, while the energy resolution can be used in event classification. The final prototype is made of high-resistivity silicon detectors, 1 mm thick with 1040 square pads with a size of 1 mm. The performance was characterized on an evaluation module featuring the same electronics and sensor material, save for sensor geometry where a sensor with 256 square pads with a side of 1.4 mm was used. The pads were read out with VATAGP7, a Gamma Medica-Ideas designed application specific integrated circuit (ASIC). The ASIC provides a logic trigger signal and an analog output for every out of 128 input channels. The measurement of the timing resolution was performed, using a positron source and a timing reference detector. A similar measurement was performed with a test pulse, ie. a charge injection into the ASIC, to study inherent resolution of the firststage electronics. We calibrated the analog output of the ASIC using standard gamma sources (241Am), and we determined the overall energy resolution. The comparators were calibrated by a test pulse, looking at the rate of triggers versus threshold. The gain variation was compensated with internal 3-bit DACs. The evaluation module was successfully characterized, exhibiting energy resolution of 1.5 keV FWHM after gain alignment. The spread of the comparator levels can be decreased below 1 keV. The timing performance allows timing windows of 20 ns to be used. Based on the performance of the evaluation module we conclude that the final prototype can be used as a PET insert probe.

Detection and spectroscopy tests of the first functional unit of a self-dependent silicon detection module constructed on the base of micro-cable and TAB technology are presented. The tests were performed using pulse-height analysis of the signals induced by gamma rays in the silicon sensor. Good shapes of the spectra and satisfactory spectroscopy resolution (given by FWHM which is less than 2 keV) correspond with results on wire bonded modules. This fact demonstrates that the micro-cable technology does not degrade performance of the detection modules and the TAB is a prospective technology for construction of small stack of self-triggered spectroscopy system suitable for medical applications where very dense packaging of sensors and front-end electronics into small volumes is necessary.

The image resolution for small animal PET systems using high energy positron emitters, such as 68Ga and 94mTc, is dominated by the positron range. The blurring caused by the positron range can be reduced through the use of an iterative reconstruction algorithm that statistically corrects for the range of the positron. This study investigates the effects of 7T magnetic fields on PET image quality while using a 3D ML-EM positron range correction algorithm in the image reconstruction.

A system for in-vivo tracking of 192Ir source during high dose rate or pulsed dose rate brachytherapy treatment was built using 1 mm thick silicon pad detectors as image sensors and knife-edge lead pinholes as collimators. With source self-images obtained from a dual-pinhole system location of the source could be reconstructed in three dimensions in real time. The system was tested with 1 Ci 192Ir clinical source in air and plexi-glass phantom. The locations of the source were tracked from a distance of 40 cm in a field of view of 20 × 20 × 20 cm3. Reconstruction precision, defined as the average distance between true and reconstructed source positions, with data collected in less than 1 second with 1 Ci 192Ir source was about 5 mm. The reconstruction precision was in our case mainly limited by imperfect alignment of detectors and pinholes. With perfect alignment the statistical error would allow precision of about 1 mm which could further be improved with larger detector placed at larger distance from the pinhole. However also the modest precision of few millimeters is sufficient for in-vivo detection of larger deviations from planned treatment caused by various misadministrations or malfunctioning of the brachytherapy treatment apparatus. Usage of silicon detectors offers a possibility for building a compact device which could be used as an independent online quality assurance system. In this paper details about sensors, readout system and reconstruction algorithm are described. Results from measurements with clinical source are presented.

Conventional SPECT cameras rely on photon-absorbing collimators to collect spatial information on radioactive source distributions thereby coupling efficiency with spatial resolution in an inverse relationship as well as causing a rapid decrease in performance with increasing incident photon energy. The Compton SPECT imaging technique replaces the conventional collimator with a position sensitive scattering detector, or “electronic” collimator. This decouples the efficiency and spatial resolution of the system and also leads to increased performance for higher energy sources. However, new technical challenges are introduced in the form of high count rates, timing resolution requirements, and complexity in the image reconstruction. A prototype system using pixelated silicon as the position sensitive scattering detector has been built to quantify the benefits realized by a Compton camera for higher energy sources in the range from 99mTc (140 keV) to the positron annihilation energy (511 keV). In order to reduce some of the technical complexities of the conventional Compton camera arrangement, the initial prototype has been configured to effectively limit the image region to a two-dimensional “slice” geometry.

There are indications that PET imaging may profit by incorporating position sensitive silicon detectors with intrinsic excellent spatial resolution into the scanner setup [1]. However, poor timing performance of detectors can compromise mentioned benefits.

This paper describes DAQ++, a C++ based framework for developing data acquisition software. The design of DAQ++ is fully object oriented (OO) and provides a hierarchy of objects that allow a full control of the acquisition system and, also, on-line monitoring and storage of data. Being an OO system, it is easy to extend the DAQ system over several machines using a CORBA based architecture which is also provided by DAQ++. Finally, the paper describes a DAQ software system, VMEDAQ, developed with DAQ++ for the data acquisition in the CIMA collaboration. It provides a GUI which controls the objects based on the DAQ++ hierarchy. VMEDAQ has been built in a modular way which allows to add dynamically user defined data producers or DAQ++ Modules and, even, data receivers or RunManagers that allow to define different data acquisition modes like, for instance, parameter scanning.

A very high-resolution small animal positron emission tomograph (PET), which can achieve sub-millimeter spatial resolution, is being developed using silicon pad detectors. The prototype PET for a single slice instrument consists of two 1 mm thick silicon pad detectors, each containing a 32×16 array of 1.4×1.4 mm pads readout with four VATAGP3 chips which have 128 channels low-noise self-triggering ASIC in each chip, coincidence units, a source turntable and tungsten slice collimator. The silicon detectors were located edgewise on opposite sides of a 4 cm field-of-view to maximize efficiency. Energy resolution is dominated by electronic noise, which is 0.98% (1.38 keV) FWHM at 140.5 keV. Coincidence timing resolution is 82.1 ns FWHM and coincidence efficiency was measured to be 1.04×10 −3 % from two silicon detectors with annihilation photons of 18 F source. Image data were acquired and reconstructed using conventional 2-D filtered-back projection (FBP) and a maximum likelihood expectation maximization (ML-EM) method. Image resolution of approximately 1.45 mm FWHM is obtained from 1-D profile of 1.1 mm diameter 18 F line source image. Even better resolution can be obtained with smaller detector element sizes. While many challenges remain in scaling up the instrument to useful efficiency including densely packed detectors and significantly improved timing resolution, performance of the test setup in terms of easily achieving sub-millimeter resolution is compelling.

Novel silicon detectors with charge gain were designed (Low Gain Avalanche Detectors - LGAD) to be used in particle physics experiments, medical and timing applications. They are based on a n++-p+-p structure where appropriate doping of multiplication layer (p^+) is needed to achieve high fields and impact ionization. Several wafers were processed with different junction parameters resulting in gains of up to 16 at high voltages. In order to study radiation hardness of LGAD, which is one of key requirements for future high energy experiments, several sets of diodes were irradiated with reactor neutrons, 192 MeV pions and 800 MeV protons to the equivalent fluences of up to Φeq=1016 cm−2. Transient Current Technique and charge collection measurements with LHC speed electronics were employed to characterize the detectors. It was found that the gain decreases with irradiation, which was attributed to effective acceptor removal in the multiplication layer. Other important aspects of operation of irradiated detectors such as leakage current and noise in the presence of charge multiplication were also investigated.

A test bench was developed to demonstrate the potential of silicon based solid-state detectors for very high resolution small animal PET. In our experiments we achieved a spatial resolution of 700 /spl mu/m FWHM and a uniform response over a wide field of view. The time resolution of the solid-state detectors as well as possible further improvements of the spatial resolution for higher energy /spl beta//sup +/ emitters using strong magnetic fields are also discussed.