Purpose The purpose of this study is to develop and validate a 3D deep learning model that predicts the final clinical diagnosis of Alzheimers disease (AD), dementia with Lewy bodies (DLB), mild cognitive impairment due to Alzheimers disease (MCI-AD), and cognitively normal (CN) using fluorine 18 fluorodeoxyglucose PET (18F-FDG PET) and compare models performance to that of multiple expert nuclear medicine physicians readers. Materials and methods Retrospective 18F-FDG PET scans for AD, MCI-AD, and CN were collected from Alzheimers disease neuroimaging initiative (556 patients from 2005 to 2020), and CN and DLB cases were from European DLB Consortium (201 patients from 2005 to 2018). The introduced 3D convolutional neural network was trained using 90% of the data and externally tested using 10% as well as comparison to human readers on the same independent test set. The models performance was analyzed with sensitivity, specificity, precision, F1 score, receiver operating characteristic (ROC). The regional metabolic changes driving classification were visualized using uniform manifold approximation and projection (UMAP) and network attention. Results The proposed model achieved area under the ROC curve of 96.2% (95% confidence interval: 90.6-100) on predicting the final diagnosis of DLB in the independent test set, 96.4% (92.7-100) in AD, 71.4% (51.6-91.2) in MCI-AD, and 94.7% (90-99.5) in CN, which in ROC space outperformed human readers performance. The network attention depicted the posterior cingulate cortex is important for each neurodegenerative disease, and the UMAP visualization of the extracted features by the proposed model demonstrates the reality of development of the given disorders. Conclusion Using only 18F-FDG PET of the brain, a 3D deep learning model could predict the final diagnosis of the most common neurodegenerative disorders which achieved a competitive performance compared to the human readers as well as their consensus.

Ultrasound is one of the most commonly used noninvasive medical imaging techniques. Ultrasound contrast agents (UCA), consisting of encapsulated gas-filled microbubbles, have shown to increase the diagnostic precision in selected low echogenic patients. UCA also holds promise for bedside evaluation of myocardial perfusion quantification, but is not yet reproducible and specific enough for clinical use. In addition risks have been addressed when used, as first recommended, together with high mechanical index (MI) for reperfusion assessment by contrast destruction. We clinically observed increased myocardial velocities after UCA-administration when applied simultaneously with color tissue Doppler imaging (CTDI) arising the question if this increase was due to physiological factors or physical changes in the backscattered signals when UCA were present.

The aims of the thesis was to explain this velocity shift and simultaneously to contribute to a future safe and contrast specific application by further characterizing the non-linear acoustic properties of UCA when located in an acoustic field. Of specific interest was to evaluate in which way nonlinear wave propagation affects the response from UCA and if a change in pulse shape, length or polarity can be utilized to increase the nonlinear signal contribution.

Twelve patients with ischemic heart disease were examined with CTDI before and after UCA-administration in order to verify the change in peak systolic velocity. An experimental in vitro model including flow and tissue phantoms for UCA was established for CTDI. Raw data from single-element transducers and clinical ultrasound systems were collected for three different UCA and analyzed to determine if the observed velocity shift could be reproduced in vitro and to find a possible cause. Our results show in vivo and in vitro that UCA will affect the autocorrelation phase shift estimator used for CTDI in terms of contribution from rupturing UCA microbubbles, which explains the velocity shift. CTDI during contrast infusion should therefore be avoided unless it can be performed at low MI where the majority of the UCA are intact.

The computational model for spatial superposition of attenuated waves was modified to include an operator for pulse distortion from nonlinear wave propagation. The Matlab™ toolbox Bubblesim based on a modified Rayleigh-Plesset-equation and with insonation parameters such as frequency, pressure amplitude, pulse length and polarity was used to study the response from single microbubbles either for simulated pulses or for pulses generated by clinical ultrasound systems and single element transducers. The combination of the two models also provided a computational platform to asses pulse distortion from nonlinear wave propagation, the response of the UCA bubble and the linear backscatter of the low amplitude bubble echo. When evaluating the harmonic response in simulations and in vitro, the interaction of the excitation pulses with the contrast bubbles was identified as the main cause of nonlinear scattering, and a 2-3 dB increase of the second harmonic amplitude depends on nonlinear distortions of the incident pulse. By applying small changes of short (<3.5 cycles) and fragmented transmitted wideband pulses of 2-2.5 MHz, it is shown that inverted pulse polarity considerably modulates power without affecting a low and safe MI (<0.4), and the results lodged promise to further to enhance a contrast response.

Quantitative assessment of regional myocardial function at rest and during stress with Doppler tissue imaging (DTI) plays an important role in daily routine echocardiography. However, reliable visual analysis is largely dependent on image quality and adequate border delineation, which still remains a challenge in a significant number of patients. In this respect, an ultrasound contrast agent (UCA) is often used to improve visualization in patients with suboptimal image quality. The knowledge of how DTI measurements will be affected by UCA present in the tissue is therefore of significant importance for an accurate interpretation of local myocardial motion. The aim of this paper was to investigate how signal contribution from UCA and nonlinear wave propagation influence the performance of the autocorrelation phase shift estimator used for DTI applications. Our results are based on model experiments with a clinical 2-D grayscale scanner and computational simulations or the DTI velocity estimator for synthetically-derived pulses, simulated bubble echoes and experimentally-sampled RF data of transmitted pulses and backscattered contrast echoes. The results show that destruction of UCA present in the tissue will give rise to an apparent bidirectional velocity bias of individual velocity estimates, but that spatial averaging of individual velocity measurements within a region-of-interest will result in a negative bias (away from the transducer) of the estimated mean or mean peak velocity. The UCA destruction will also have a significant impact on the measured integrated mean velocity over time, i.e., displacement. To achieve improved visualization with UCA during DTI-examinations, we either recommend that it is performed at low acoustic powers, mechanical index <= 0.3, thereby minimizing the effects from bubble rupture, or that each Doppler pulse package is preceded by a destruction burst similar to "Flash imaging" to clear the target area of contrast microbubbles.

The combination of Doppler tissue imaging and myocardial contrast echocardiography has the potential to provide information about motion and perfusion of the myocardium in a single examination. The purpose of this study was to establish how the presence of ultrasound contrast agent (UCA) affects measurements of Doppler tissue velocities in vivo and in vitro. We performed echocardiography in 12 patients with ischemic heart disease before and immediately after a slow intravenous infusion of the UCA Optison, using color Doppler tissue imaging to examine the effect of contrast agents in vivo. The myocardial peak systolic velocities and their integrals were analyzed in digitally stored cineloops before and after contrast administration. To distinguish between methodologic and physiologic factors affecting the measurement of tissue velocity in vitro, experiments with a rotating disk and a flow cone phantom were also carried out for the 3 contrast agents: Optison, Sonovue, and Sonazoid. In vivo results show that the values for peak systolic velocity increased by about 10% during contrast infusion, from mean 5.2 ± 1.8 to 5.7 ± 2.3 cm/s (P = .02, 95% confidence interval 2%-16%). The increase in myocardial peak systolic velocities was verified in experimental models in which the UCA increased the estimated mean velocity in the order of 5% to 20% for the motion interval of 5 to 7 cm/s, corresponding to the myocardial velocities studied in vivo. The response was similar for all 3 contrast agents and was not affected by moderate variations in concentration of the agent. We have shown that the presence UCA will affect Doppler tissue measurements in vivo and in vitro. The observed bias is presumed to be an effect of harmonic signal contribution from rupturing contrast agent microbubbles and does not indicate biologic or physiologic effects. Copyright 2006 by the American Society of Echocardiography.

Phosphorus-31 NMR spectroscopy using slice selection (DRESS) was used to investigate the absolute concentrations of metabolites in the human liver. Absolute concentrations provide more specific biochemical information compared to spectrum integral ratios. Nine patients with histopathologically proven diffuse liver disease and 12 healthy individuals were examined in a 1.5-T MR scanner (GE Signa LX Echospeed plus). The metabolite concentration quantification procedures included: (1) determination of optimal depth for the in vivo measurements, (2) mapping the detection coil characteristics, (3) calculation of selected slice and liver volume ratios using simple segmentation procedures and (4) spectral analysis in the time domain. The patients had significantly lower concentrations of phosphodiesters (PDE), 6.3±3.9 mM, and ATP-β, 3.6±1.1 mM, (P<0.05) compared with the control group (10.0±4.2 mM and 4.2±0.3 mM, respectively). The concentrations of phosphomonoesters (PME) were higher in the patient group, although this was not significant. Constructing an anabolic charge (AC) based on absolute concentrations, [PME]/([PME] + [PDE]), the patients had a significantly larger AC than the control subjects, 0.29 vs. 0.16 (P<0.005). Absolute concentration measurements of phosphorus metabolites in the liver are feasible using a slice selective sequence, and the technique demonstrates significant differences between patients and healthy subjects.