The detection of cancer lesions of a comparable size to that of the typical system resolution of modern scanners is a long-standing problem in Positron Emission Tomography. In this paper, the effect of composing an image-registering convolutional neural network with the modeling of the static data acquisition (i.e., the forward model) is investigated. Two algorithms for Positron Emission Tomography reconstruction with motion and attenuation correction are proposed and their performance is evaluated in the detectability of small pulmonary lesions. The evaluation is performed on synthetic data with respect to chosen figures of merit, visual inspection, and an ideal observer. The commonly used figures of merit—Peak Signal-to-Noise Ratio, Recovery Coefficient, and Signal Difference-to-Noise Ration—give inconclusive responses, whereas visual inspection and the Channelised Hotelling Observer suggest that the proposed algorithms outperform current clinical practice.

We have adapted, implemented and trained the Learned Primal Dual algorithm suggested by Adler and Öktem and evaluated its performance in reconstructing projection data from our PET scanner. Learned Primal Dual reconstructions are compared to Maximum Likelihood Expectation Maximisation (MLEM) reconstructions. Different strategies for training are also compared. Whenever the noise level of the data to reconstruct is sufficiently represented in the training set, the Learned Primal Dual algorithm performs well on the recovery of the activity concentrations and on noise reduction as compared to MLEM. The algorithm is also shown to be robust against the appearance of artefacts, even when the images that are to be reconstructed present features were not present in the training set. Once trained, the algorithm reconstructs images in few seconds or less. 

In this work, we present an efficient methodology for multigrid tomographic image reconstruction from non-truncated projection data. By partitioning the reconstruction domain and adapting the forward and backward operators, an image can be reconstructed accurately within multiple domains of varying discretisation or regularisation. We demonstrate the efficacy of the multigrid reconstruction principle using simulated data for quantitative assessment and experimental measurements from a μ-CT scanner for a clinically relevant use case scenario. A major advantage of using multiple reconstruction grids is the possibility to drastically reduce the number of unknowns in the inverse problem, and thereby the associated computational cost. This cost reduction helps to enlarge the class of available algorithms in applications with strict limitations on computation time or resources, and it enables full system resolution reconstruction of subregions that would otherwise be infeasible for the full field of view. The numerical experiments, along with a brief error analysis, show that the expected artefacts from coarse discretisation outside the region of interest become noticeable only for large differences in discretisation between subregions.

Vascular pressure differences are established risk markers for a number of cardiovascular diseases. Relative pressures are, however, often driven by turbulence-induced flow fluctuations, where conventional non-invasive methods may yield inaccurate results. Recently, we proposed a novel method for non-turbulent flows, νWERP, utilizing the concept of virtual work-energy to accurately probe relative pressure through complex branching vasculature. Here, we present an extension of this approach for turbulent flows: νWERP-t. We present a theoretical method derivation based on flow covariance, quantifying the impact of flow fluctuations on relative pressure. νWERP-t is tested on a set of in-vitro stenotic flow phantoms with data acquired by 4D flow MRI with six-directional flow encoding, as well as on a patient-specific in-silico model of an acute aortic dissection. Over all tests νWERP-t shows improved accuracy over alternative energy-based approaches, with excellent recovery of estimated relative pressures. In particular, the use of a guaranteed divergence-free virtual field improves accuracy in cases where turbulent flows skew the apparent divergence of the acquired field. With the original νWERP allowing for assessment of relative pressure into previously inaccessible vasculatures, the extended νWERP-t further enlarges the method's clinical scope, underlining its potential as a novel tool for assessing relative pressure in-vivo.

A photodiode-based inexpensive detector working as counter and spectrometer for alpha particles, named Alphaino, is described and analyzed in depth. Prior to detector construction, Monte Carlo simulations by means of MCNPX ver. 2.7.0 code have been carried out to select the most suitable sensitive element for the intended applications. The detector has been tested for low-rate alpha-particle counting and spectroscopy, demonstrating a maximum achievable count rate of 4⋅103 s−1, with an energy resolution corresponding to a Full Width Half Maximum of 160keV over the entire energy range of measured alpha, namely 4−6.5 MeV, the intrinsic efficiency being 100%. Alphaino can be used for fast and qualitative analyses to radionuclides identification, and quantitative analyses when radionuclides monitored are characterized by well distinguished energy lines in spectra. Its applications will include 222Rn progeny monitoring by mechanical air sampling on a millipore filter, and disposable applications to qualitative measuring of potentially alpha-contaminated liquids (containing plutonium isotopes) by a droplet put on the photodiode itself, for a quick and cheap evaluation prior to initiate proper chemical treatments to classical alpha spectrometry by electrodeposition. Alphaino is completely open-source. The repository for the project is available on GITHUB at https://github.com/bemxgm/Radon-Monitor.

Many cardiovascular diseases lead to local increases in relative pressure, reflecting the higher costs of driving blood flow. The utility of this biomarker for stratifying the severity of disease has thus driven the development of methods to measure these relative pressures. While intravascular catheterisation remains the most direct measure, its invasiveness limits clinical application in many instances. Non-invasive Doppler ultrasound estimates have partially addressed this gap; however only provide relative pressure estimates for a range of constricted cardiovascular conditions. Here we introduce a non-invasive method that enables arbitrary interrogation of relative pressures throughout an imaged vascular structure, leveraging modern phase contrast magnetic resonance imaging, the virtual work-energy equations, and a virtual field to provide robust and accurate estimates. The versatility and accuracy of the method is verified in a set of complex patient-specific cardiovascular models, where relative pressures into previously inaccessible flow regions are assessed. The method is further validated within a cohort of congenital heart disease patients, providing a novel tool for probing relative pressures in-vivo.

The hybrid imaging combines the anatomical information with the functional or metabolic information using different conventional single imaging modalities improving the overall diagnosis outcome of the clinical examination. Since the introduction of the first hybrid imaging device PET-CT in 1998 different combinations of hybrid imaging were developed such as PET-MRI, SPECT-CT.

However, lack of multimodal contrast agent specifically aimed for hybrid imaging limits the diagnostic outcome of these novel techniques. Initial attempts in fabrication of hybrid contrast agents were made by combining previously existing single modal contrast agents into one. In this study, polyvinyl alcohol (PVA) microbubbles (MB) and gold nanoparticles - which by themselves are already established contrast agents used in preclinical studies for ultrasound and CT, respectively - were chosen as parent contrast agents to fabricate the dual modal Contrast Agent for UltraSound and CT (CACTUS).

Method

The fabrication of MBs was adapted from Cavalieri et al.[1]. PVA powder (Sigma Aldrich, MO USA) was dissolved in the water at 80°C. The aqueous PVA-chains were cleaved by sodium metaperiodate (NaIO4, purity>99.0%, Sigma Aldrich, MO USA). Vigorous stirring force was applied to the resulting telechelic aldehydic PVA-chains for 2 hours to crosslink the telechelic aldehydic PVA-chains and form the PVA-coated MBs at the water-air interface.

CACTUS MBs were synthesized in a similar fashion to the above, but adding gold nanoparticles (diameter 1.9nm, Nanoprobes, NY, USA) during formation of the MBs.

The size distributions of MBs and CACATUS MBs were determined using an optical microscope (ECLIPSE Ci-S, Nikon, Tokyo, Japan) and a Neubauer counting chamber (Brand GmbH, Wertheim, Germany).

The acoustic attenuation coefficients of the MBs suspension were acquired at peak negative pressure (PNP) from 10 - 300 kPa. Three MBs suspension samples with concentrations of (sample A),  (sample B) and  ml^-1 (sample C) were prepared and loaded in a 1 cm thick two-cavity chamber. A flat single crystal ultrasound transducer with central frequency 3.5MHz was used to generate the ultrasound beam. The amplitude of received echoes through samples and water were compared at the fundamental frequency, as well as the 2^nd and 3^rd harmonic for each value of the concentration used.

The mass attenuation of water, suspension of gold nanoparticles with concentration 160mg/L, plain MBs, and CACTUS MBs, was measured by quantum FX-CT micro-CT (PerkinElmer Inc, MA, USA). The micro-CT was operated at a current of 200mA with exposure time of 120s and varied voltage 50kV, 70kV and 90kV. Each 3D image has a size of 512*512*512 pixels or 75.8*75.8*75.8 mm. Contrast to noise ratios (CNR) between water and all samples were calculated following Eq. 1.Where S(x,y,z) and W(x,y,z) are the mass attenuation of the sample and water per voxel, respectively. ns(x,y,z) and nw(x,y,z) are the noise function with zero mean of sample and water respectively. M_s and M_w are the mean mass attenuation acquired for the sample and water in the volume of interest. The σ_s² and σ_w² are the variance of the mass attenuation read out of the sample and water in the volume of interested.

In addition to the gas-core MBs for the CT tests, liquid-core gold loaded capsules were synthesized in two steps. In the first step, PVA shelled liquid-core capsules were obtained by exposing MBs to 66% v/v ethanol solution. In the second step, the resulting liquid-core capsules were mixed with high concentration gold nanoparticles suspension and homogenized by a shaker (MS 3 basic, IKA, Königswinter Germany) at 500rpm for 1 hour for goal loading. The resulting gold loaded capsules were washed with Milli-Q water using centrifuge (Galaxy 5D digital microcentrifuge, VWR, USA) at a speed of 1000 g for 5 min.

Results and discussion

The mean diameter of MBs is 3.6±1.1 μm. The mean diameter of CACTUS MBs is 3.2±0.7 μm. The size distribution of the gold loaded capsules was not investigated separately, but rather assumed identical to the plain MBs. The number and the volume distribution of MBs and CACTUS MBs are shown in figure 1. The results demonstrate that most of the CACTUS MBs and MBs have a diameter from 1 to 6 μm. Therefore, they are able pass through the capillaries and will resonate within typical clinical diagnostic ultrasound frequency below 15 MHz.

Pressure dependent acoustic attenuation coefficients of the sample A, B, and C are shown in figure 2. The results show that attenuation coefficients of sample A and B at the fundamental frequency stay constant and slightly increase at the second harmonic at the PNP below 100kPa, indicating a linear oscillation of MBs. As the PNP reaches 200kPa, the attenuation coefficient of sample A at fundamental frequency decreases while at 2^nd and 3^rd harmonics increases, indicating that the energy of the echo shifts from the fundamental frequency to the 2^nd and 3^rd harmonics. As the PNP goes higher to 300kPa, the attenuation coefficient of sample A at the fundamental frequency, 2^nd, and 3^rd harmonics decreases, suggesting that the energy shifts to an even higher harmonic. At the same time, the attenuation coefficient of sample B stays constant at fundamental frequency, decreases at 2^nd harmonics, and increases at the 3^rd harmonic, suggesting the energy starts to shift to the 3^rd harmonic. The attenuation coefficient of sample C at fundamental frequency, 2^nd and 3^rd harmonics keep constant and low due to low sample concentration. The test reveals the energy shifting of the echo to the higher harmonics at PNP higher than 100 kPa, indicating the nonlinear oscillation of MBs at PNP higher than 100 kPa. Moreover, the concentration of the MBs seems to influence the energy shifting: the higher the concentration the earlier the shift to the higher harmonics occurs, in the range of the concentration consider in this study.

The pilot results of the micro-CT tests are presented in Table 1. The reference, gold nanoparticles solution, has the highest CNR per voxel at all CT operating voltages. The CNR per voxel of CACTUS MBs suspensions is below 0.1, virtually equaling the MBs at all operating voltages, suggesting that no gold or very little gold were loaded into the shell of the CACTUS MBs. The gold loaded capsules suspension has higher CNR per voxel than the capsule supernatant (the surrounding environment of capsules) and the MBs suspension, implying that the gold nanoparticles were loaded into the capsules. However, it is not clear whether the gold nanoparticles were loaded in the core of the MBs or in the MBs shell. The expected sharp increase of CNR per voxel at the k-edge of gold did not appear. We believe that is because even at our highest operating voltage of 90kV, the percentage of the photons with energy higher than 80.7 keV is still low. Introduction of a high-pass metal filter could increase the percentage of high energy photon. On the other hand, the metal filter will reduce the total number of the photons which would increase the noise of the images. Since same current was applied on every CT test, less X-ray photons reached the sensors when the CT was operated at low voltage. Therefore, it might be worth performing additional calibration tests to adjust the operating currents to make sure that the numbers of the photons that reach the sensor at every operating voltage are the same.

Conclusion

In this study, the CACTUS MBs and gold loaded capsules were fabricated as potential candidates for dual modal contrast agent. The characterization revealed that gold loaded capsule is a promising initial step. Nevertheless, the method to convert back liquid-core capsules to gas-core MBs needs to be established.

[1] Cavalieri, F., El Hamassi, A., Chiessi, E., Paradossi, G., Villa, R., & Zaffaroni, N. (2006). Tethering functional ligands onto shell of ultrasound active polymeric microbubbles. Biomacromolecules, 7(2), 604-611.

Echocardiography is the most commonly used image modality in cardiology, assessing several aspects of cardiac viability. The importance of cardiac hemodynamics and 4D blood flow motion has recently been highlighted, however such assessment is still difficult using routine echo-imaging. Instead, combining imaging with computational fluid dynamics (CFD)-simulations has proven valuable, but only a few models have been applied clinically. In the following, patient-specific CFD-simulations from transthoracic dobutamin stress echocardiography have been used to analyze the left ventricular 4D blood flow in three subjects: two with normal and one with reduced left ventricular function. At each stress level, 4D-images were acquired using a GE Vivid E9 (4VD, 1.7MHz/3.3MHz) and velocity fields simulated using a presented pathway involving endocardial segmentation, valve position identification, and solution of the incompressible Navier-Stokes equation. Flow components defined as direct flow, delayed ejection flow, retained inflow, and residual volume were calculated by particle tracing using 4th-order Runge-Kutta integration. Additionally, systolic and diastolic average velocity fields were generated. Results indicated no major changes in average velocity fields for any of the subjects. For the two subjects with normal left ventricular function, increased direct flow, decreased delayed ejection flow, constant retained inflow, and a considerable drop in residual volume was seen at increasing stress. Contrary, for the subject with reduced left ventricular function, the delayed ejection flow increased whilst the retained inflow decreased at increasing stress levels. This feasibility study represents one of the first clinical applications of an echo-based patient-specific CFD-model at elevated stress levels, and highlights the potential of using echo-based models to capture highly transient flow events, as well as the ability of using simulation tools to study clinically complex phenomena. With larger patient studies planned for the future, and with the possibility of adding more anatomical features into the model framework, the current work demonstrates the potential of patient-specific CFD-models as a tool for quantifying 4D blood flow in the heart.