Hybrid imaging with [68Ga]PSMA-11 PET-CT and PET-MRI in biochemically recurrent prostate cancer.

AIM: To compare [68Ga]PSMA-11 PET-CT, [68Ga]PSMA-11 PET-MRI and MRI in a cohort of prostate cancer (PCa) patients in biochemical recurrence after initial curative therapy. MATERIALS AND METHODS: Fifty-three patients with biochemically recurrent PCa underwent whole-body [68Ga]PSMA-11 PET-CT 1 hour post-injection (p.i.) followed by [68Ga]PSMA-11 PET-MRI 2.5 hours p.i., including a multiparametric MRI pelvic protocol examination. Imaging data analysis consisted of visual (qualitative) evaluation of the PET-CT, PET-MRI and MRI scans, as well as semi-quantitative and quantitative analyses of the PET and MRI data, including calculation of the parameters standardized uptake value (SUV) and apparent diffusion coefficient (ADC) derived from the PCa lesions. Association analysis was performed between imaging and clinical data, including PSA level and Gleason score. The results were considered significant for p-values less than 0.05 (p < 0.05). RESULTS: The hybrid imaging modalities [68Ga]PSMA-11 PET-CT and PET-MRI were positive in more patients than MRI alone. In particular, PET-CT detected lesions suggestive of PCa relapse in 34/53 (64.2%), PET-MRI in 36/53 (67.9%) and MRI in 23/53 patients (43.4%). While no significant differences in lesion detection rate were observed between PET-CT and PET-MRI, the latter was particularly efficient in detection of local recurrences in the prostate bed mainly due to the contribution of the MRI part of the modality. Association analysis revealed a statistically significant increase in the probability of a positive scan with increasing PSA levels for all imaging modalities. Accordingly, there was no significant association between scan positivity rate and Gleason score for any imaging modality. No significant correlation was observed between SUV and ADC values in lymph node metastases. CONCLUSION: [68Ga]PSMA-11 PET-CT and PET-MRI provide equally good detection rates for PCa recurrence, both outperforming stand-alone MRI.

Influence of diffusion on transverse relaxation rates and phases of an ensemble of magnetic spheres.

In quantitative susceptibility mapping, the tissue susceptibility is determined from the magnitude and phase of the gradient echo signal, which is influenced by the interplay of complex susceptibility and diffusion effect. Herein, we analytically analyze the influence of diffusion on magnitude and phase images generated by randomly arranged magnetic spheres as a model of intracerebral iron depositions. We demonstrate that both gradient and spin echo relaxation rate constants have a strong and nonlinear dependence on diffusion strength and give empirical formulas for magnitude and phase. This may be used in the future to improve QSM processing methods. In addition, we show that, in theory, combined acquisitions of gradient and spin echo can be used to determine the dimension of the magnetic spheres and the diffusion strength.

Spin echo formation in muscle tissue.

Determination of the spin echo signal evolution and of transverse relaxation rates is of high importance for microstructural modeling of muscle tissue in magnetic resonance imaging. So far, numerically exact solutions for the NMR signal dynamics in muscle tissue models have been reported only for the gradient echo free induction decay, with spin echo problems usually solved by approximate methods. In this work, we modeled the spin echo signal numerically exact by discretizing the radial dimension of the Bloch-Torrey equation and expanding the angular dependency in terms of even Chebyshev polynomials. This allows us to express the time dependence of the local magnetization as a closed-form matrix expression. Using this method, we were able to accurately capture the spin echo local and total magnetization dynamics. The obtained transverse relaxation rates showed a high concordance with random walker and finite-element simulations. We could demonstrate that in cases of smaller diffusion coefficients, the commonly used strong collision approximation significantly underestimates the true value considerably. Instead, the limiting behavior in this regime is correctly described either by the full solution or by the slow diffusion approximation. Experimentally measured transverse relaxation rates of a mouse limb muscle showed an angular dependence in accordance with the theoretical prediction.

Threshold-dependent iodine imaging and spectral separation in a whole-body photon-counting CT system.

OBJECTIVE: To evaluate the dual-energy (DE) performance and spectral separation with respect to iodine imaging in a photon-counting CT (PCCT) and compare it to dual-source CT (DSCT) DE imaging. METHODS: A semi-anthropomorphic phantom extendable with fat rings equipped with iodine vials is measured in an experimental PCCT. The system comprises a PC detector with two energy bins (20 keV, T) and (T, eU) with threshold T and tube voltage U. Measurements using the PCCT are performed at all available tube voltages (80 to 140 kV) and threshold settings (50-90 keV). Further measurements are performed using a conventional energy-integrating DSCT. Spectral separation is quantified as the relative contrast media ratio R between the energy bins and low/high images. Image noise and dose-normalized contrast-to-noise ratio (CNRD) are evaluated in resulting iodine images. All results are validated in a post-mortem angiography study. RESULTS: R of the PC detector varies between 1.2 and 2.6 and increases with higher thresholds and higher tube voltage. Reference R of the EI DSCT is found as 2.20 on average overall phantoms. Maximum CNRD in iodine images is found for T = 60/65/70/70 keV for 80/100/120/140 kV. The highest CNRD of the PCCT is obtained using 140 kV and is decreasing with decreasing tube voltage. All results could be confirmed in the post-mortem angiography study. CONCLUSION: Intrinsically acquired DE data are able to provide iodine images similar to conventional DSCT. However, PCCT thresholds should be chosen with respect to tube voltage to maximize image quality in retrospectively derived image sets. KEY POINTS: • Photon-counting CT allows for the computation of iodine images with similar quality compared to conventional dual-source dual-energy CT. • Thresholds should be chosen as a function of the tube voltage to maximize iodine contrast-to-noise ratio in derived image sets. • Image quality of retrospectively computed image sets can be maximized using optimized threshold settings.

Photon-counting detectors in computed tomography: from quantum physics to clinical practice.

Over the last decade, a fundamentally new type of computed tomography (CT) detectors has proved its superior capabilities in both physical and preclinical evaluations and is now approaching the stage of clinical practice. These detectors are able to discriminate single photons and quantify their energy and are hence called photon-counting detectors. Among the promising benefits of this technology are improved radiation dose efficiency, increased contrast-to-noise ratio, reduced metal artifacts, improved spatial resolution, simultaneous multi-energy acquisitions, and the prospect of multi-phase imaging within a single acquisition using multiple contrast agents. Taking the conventional energy-integrating detectors as a reference, the authors demonstrate the technical principles of this new technology and provide phantom and patient images acquired by a whole-body photon-counting CT. These images serve as a basis for discussing the potential future of clinical CT.

Potential of ultra-high-resolution photon-counting CT of bone metastases: initial experiences in breast cancer patients.

Conventional CT scanners use energy-integrating detectors (EIDs). Photon-counting detector (PCD) computed tomography (CT) utilizes a CT detector technology based on smaller detector pixels capable of counting single photons and in addition discriminating their energy. Goal of this study was to explore the potential of higher spatial resolution for imaging of bone metastases. Four female patients with histologically confirmed breast cancer and bone metastases were included between July and October 2019. All patients underwent conventional EID CT scans followed by a high resolution non-contrast experimental PCD CT scan. Ultra-high resolution (UHR) reconstruction kernels were used to reconstruct axial slices with voxel sizes of 0.3 mm × 0.3 mm (inplane) × 1 mm (z-direction). Four radiologists blinded for patient identity assessed the images and compared the quality to conventional CT using a qualitative Likert scale. In this case series, we present images of bone metastases in breast cancer patients using an experimental PCD CT scanner and ultra-high-resolution kernels. A tendency to both a smaller inter-reader variability in the structural assessment of lesion sizes and in the readers' opinion to an improved visualization of lesion margins and content was observed. In conclusion, while further studies are warranted, PCD CT has a high potential for therapy monitoring in breast cancer.

A semi-automated quantitative comparison of metal artifact reduction in photon-counting computed tomography by energy-selective thresholding.

An evaluation of energy thresholding and acquisition mode for metal artifact reduction in Photon-counting detector CT (PCD-CT) compared to conventional energy-integrating detector CT (EID-CT) was performed. Images of a hip prosthesis phantom placed in a water bath were acquired on a scanner with PCD-CT and EID-CT (tube potentials: 100, 120 and 140 kVp) and energy thresholds (above 55-75 keV) in Macro and Chess mode. Only high-energy threshold images (HTI) were used. Metal artifacts were quantified by a semi-automated segmentation algorithm, calculating artifact volumes, means and standard deviations of CT numbers. Images of a human cadaver with hip prosthesis were acquired on the PCD-CT in Macro mode as proof-of-concept. Images at 140 kVp showed less metal artifacts than 120 kVp or 100 kVp. HTI (70, 75 keV) had fewer artifacts than low energy thresholds (55, 60, 65 keV). Fewer artifacts were observed in the Macro-HTI (8.9-13.3%) for cortical bone compared to Chess-HTI (9.4-19.1%) and EID-CT (10.7-19.0%) whereas in bone marrow Chess-HTI (19.9-45.1%) showed less artifacts compared to Macro-HTI (21.9-38.3%) and EID-CT (36.4-54.9%). Noise for PCD-CT (56-81 HU) was higher than EID-CT (33-36 HU) irrespective of tube potential. High-energy thresholding could be used for metal artifact reduction in PCD-CT, but further investigation of acquisition modes depending on target structure is required.

[Microvascular changes in COVID-19]. / Mikrovaskuläre Veränderungen bei COVID-19.

BACKGROUND: Clinically, coronavirus disease 2019 (COVID-19) is associated with a wide range of symptoms, which can range from mild complaints of an upper respiratory infection to life-threatening hypoxic respiratory insufficiency and multiorgan failure. OBJECTIVE: The initially identified pulmonary damage patterns, such as diffuse alveolar damage in acute lung failure, are accompanied by new findings that draw a more complex scenario. These include microvascular involvement and a wide range of associated pathologies of multiple organ systems. A back-scaling of microstructural vascular changes is possible via targeted correlation of pathological autopsy results with radiological imaging. MATERIAL AND METHODS: Radiological and pathological correlation as well as microradiological imaging to investigate microvascular involvement in fatal COVID-19. RESULTS: The cases of two COVID-19 patients are presented. Patient 1 showed a relative hypoperfusion in lung regions that did not have typical COVID-19 infiltrates; the targeted post-mortem correlation also showed subtle signs of microvascular damage even in these lung sections. Patient 2 showed both radiologically and pathologically advanced typical COVID-19 destruction of lung structures and the case illustrates the damage patterns of the blood-air barrier. The perfusion deficit of the intestinal wall shown in computed tomography of patient 2 could not ultimately clearly be microscopically attributed to intestinal microvascular damage. CONCLUSION: In addition to microvascular thrombosis, our results indicate a functional pulmonary vasodysregulation as part of the pathophysiology during the vascular phase of COVID-19. The clinical relevance of autopsies and the integration of radiological imaging findings into histopathological injury patterns must be emphasized for a better understanding of COVID-19.

Iodine contrast-to-noise ratio improvement at unit dose and contrast media volume reduction in whole-body photon-counting CT.

PURPOSE: To assess the dose-normalized iodine contrast-to-noise-ratio (CNRD) improvement and contrast media reduction potential obtained with photon-counting (PC) CT compared to conventional energy-integrating (EI) CT as a function of patient size and tube voltage. METHOD: Images of a semi-anthropomorphic phantom of different sizes (small, medium, large) equipped with vials containing different iodine concentrations were acquired at the SOMATOM CounT prototype CT system using tube voltages of 80 kV-140 kV. CNRD is evaluated in reconstructions obtained using the EI detector, the PC detector using a single bin, and in reconstructions obtained by statistically optimally weighting acquisitions with two bins. Iodine CNRD improvements, potential dose reduction and the potential contrast media volume reduction are reported. RESULTS: In general, iodine CNRD improvement increases with increasing tube voltage for all patient sizes. In particular, if only one energy bin is used, the CNRD improvement is up to 30 % (small: 10 %, medium: 18 %, large: 30 %) and up to 37 % if an optimal weighting of two bins is performed (small: 13 %, medium: 25 %, large: 37 %) which is equivalent to the potential contrast media volume reduction. The improved iodine CNRD of PC compared to EI may allow for a potential radiation dose reduction of up to 46 %. CONCLUSIONS: All patients' iodine contrast at given x-ray dose, and particularly medium and large sized patients acquired at higher tube voltages, may benefit from photon-counting CT. The iodine contrast improvement can be used to reduce patient dose or to reduce the amount of contrast agent that is administered.

Spin echoes: full numerical solution and breakdown of approximative solutions.

The spin echo signal from vessels in Krogh's capillary model as well in the random distribution vessel model are studied by numerically solving the Bloch-Torrey equation. A comparison is made with the Gaussian local phase approximation, the Gaussian phase approximation and the strong-collision approximation. Differences between the Gaussian local phase approximation and the Gaussian phase approximation are explained. In the intermediate diffusion regime, the full numerical solution shows oscillations which are absent in any of the approximate solutions. In the limit of large diffusion coefficients, where the approximations become exact, the signal shows a linear-exponential decay governed by a single parameter. The features of the exact numerical solution can be explained by an analytically solvable discrete two-level model. There is a one-to-one correspondence between the different diffusion regimes and the three cases of the damped harmonic oscillator.

Dependence of the frequency distribution around a vessel on the voxel orientation.

In this work the frequency distribution around a vessel inside a cubic voxel is investigated. Therefore, the frequency distribution is calculated in dependence on the orientation of the voxel according to the external magnetic field. The frequency distribution exhibits an interesting peak structure that cannot be explained by the established Krogh's vessel model. The results were validated with phantom measurements and in vivo measurements that agree very well with the developed theory.

Pseudo-diffusion effects in lung MRI.

Magnetic resonance imaging of lung tissue is strongly influenced by susceptibility effects between spin-bearing water molecules and air-filled alveoli. The measured lineshape, however, also depends on the interplay between susceptibility effects and blood-flow around alveoli that can be approximated as pseudo-diffusion. Both effects are quantitatively described by the Bloch-Torrey-equation, which was so far only solved for dephasing on the alveolar surface. In this work, we extend this model to the whole range of physiological relevant air volume fractions. The results agree very well with in vivo measurements in human lung tissue.

Spin dephasing around randomly distributed vessels.

We analyze the gradient echo signal in the presence of blood vessel networks. Both, diffusion and susceptibility effects are analytically emphasized within the Bloch-Torrey equation. Solving this equation, we present the first exact description of the local magnetization around a single vessel. This allows us to deduce the gradient echo signal of parallel vessels randomly distributed in a plane, which is valid for arbitrary mean vessel diameters in the range of physiological relevant blood volume fractions. Thus, the results are potentially relevant for gradient echo measurements of blood vessel networks with arbitrary vessel size.

Diffusion effects in myelin sheath free induction decay.

Myelin sheath microstructure and composition produce MR signal decay characteristics that can be used to evaluate status and outcome of demyelinating disease. We extend a recently proposed model of neuronal magnetic susceptibility, that accounts for both the structural and inherent anisotropy of the myelin sheath, by including the whole dynamic range of diffusion effects. The respective Bloch-Torrey equation for local spin dephasing is solved with a uniformly convergent perturbation expansion method, and the resulting magnetization decay is validated with a numerical solution based on a finite difference method. We show that a variation of diffusion strengths can lead to substantially different MR signal decay curves. Our results may be used to adjust or control simulations for water diffusion in neuronal structures.

Spin dephasing in the Gaussian local phase approximation.

The Brownian motion of spins diffusing in an inhomogeneous magnetic field created by susceptibility effects is considered. Applying the correct form of the Gaussian approximation, the method allows calculating the local magnetization as well as the free induction decay for all diffusion regimes. The phase accumulated during the diffusional motion is treated by an averaging over all possible trajectories in terms of the Gaussian local phase approximation. Predictions of the Gaussian local phase approximation are compared with the Gaussian phase approximation for diffusion in a constant gradient in a slab, a cylinder, and a sphere. The Gaussian local phase approximation, thereby, shows several advantages compared to the Gaussian phase approximation: it is also valid in the static dephasing regime, predicts correctly both transverse components of the magnetization, and yields information about the local magnetization.

The influence of spatial patterns of capillary networks on transverse relaxation.

Tissue-inherent relaxation parameters offer valuable information about the arrangement of capillaries: in an external field, capillaries act as magnetic perturbers to generate local inhomogeneous fields due to the susceptibility difference of deoxygenated blood and the surrounding tissue. These field inhomogeneities influence the free induction decay in a characteristic way, and, conversely, the above tissue parameters can be recovered by multi-parametric fits of adequate theoretical models to experimentally sampled free induction decays. In this work we study the influence of different spatial patterns of capillary positions on the free induction decay. Starting from the standard single capillary approximation (Krogh cylinder) for a symmetric array of capillaries, the free induction decay is analyzed for increasingly random capillary positions, using a previously described Gibbs point field model. The effects of diffusion are implemented with a flexible and fast random walk simulation. We find that the asymmetric form of the obtained frequency distribution is more robust against variations of capillary radii than against shifts of capillary positions, and further that, for an inclusion of diffusion effects, the single capillary approximation models the uniform alignment of capillaries in the hexagonal lattice to great accuracy. An increase in randomization of capillary positions then leads to a significant change in relaxation times. This effect, however, is found less pronounced than that of changes in the off-resonance field strengths which are controlled by the oxygen extraction fraction, thus indicating that observed changes in BOLD imaging are more likely to be attributed to changes in oxygenation than to capillary alignment.

Dephasing and diffusion on the alveolar surface.

We propose a surface model of spin dephasing in lung tissue that includes both susceptibility and diffusion effects to provide a closed-form solution of the Bloch-Torrey equation on the alveolar surface. The nonlocal susceptibility effects of the model are validated against numerical simulations of spin dephasing in a realistic lung tissue geometry acquired from synchotron-based µCT data sets of mouse lung tissue, and against simulations in the well-known Wigner-Seitz model geometry. The free induction decay is obtained in dependence on microscopic tissue parameters and agrees very well with in vivo lung measurements at 1.5 Tesla to allow a quantification of the local mean alveolar radius. Our results are therefore potentially relevant for the clinical diagnosis and therapy of pulmonary diseases.

Spin dephasing in a magnetic dipole field around large capillaries: Approximative and exact results.

We present an analytical solution of the Bloch-Torrey equation for local spin dephasing in the magnetic dipole field around a capillary and for ensembles of capillaries, and adapt this solution for the study of spin dephasing around large capillaries. In addition, we provide a rigorous mathematical derivation of the slow diffusion approximation for the spin-bearing particles that is used in this regime. We further show that, in analogy to the local magnetization, the transverse magnetization of one MR imaging voxel in the regime of static dephasing (where diffusion effects are not considered) is merely the first term of a series expansion that constitutes the signal in the slow diffusion approximation. Theoretical results are in agreement with experimental data for capillaries in rat muscle at 7T.

CPMG relaxation rate dispersion in dipole fields around capillaries.

Transverse relaxation rates for Carr-Purcell-Meiboom-Gill (CPMG) sequences increase with inter-echo time in presence of microscopic magnetic field inhomogeneities due to nuclear spin diffusion. For a weak field approximation that includes diffusion effects, the CPMG relaxation rate shift for proton diffusion around capillaries in muscle tissue can be expressed in terms of a frequency correlation function and the inter-echo time. The present work provides an analytical expression for the local relaxation rate shift that is dependent on local blood volume fraction, diffusion coefficient, capillary radius, susceptibility difference and inter-echo time. Asymptotic regions of the model are in agreement with previous modeling results of Brooks et al., Luz et al. and Ziener et al. In comparison with simulation data, the model shows an equal or better accuracy than established approximations. Also, model behavior coincides with experimental data for rat heart and skeletal muscle. The present work provides analytical tools to extract sub-voxel information about uniform capillary networks that can be used to study capillary organization or micro-circulatory remodeling.

[Principles and applications of susceptibility weighted imaging]. / Grundlagen und Anwendungen der suszeptibilitätsgewichteten Bildgebung.

BACKGROUND: Susceptibility-weighted imaging (SWI), initially developed to provide an improved method for cerebral magnetic resonance (MR) venography, is now an integral part of neuroradiological diagnostics and is steadily gaining importance in non-cerebral imaging. PRINCIPLES: Tissue-inherent susceptibility differences generate a local magnetic field in which the dephasing of signal-producing protons occurs. This leads to a characteristic phase shift that can be used as a means to enhance contrast in the well-known T2*-weighted imaging. APPLICATION IN CLINICAL ROUTINE: Many medically relevant pathologies induce tissue alterations that also influence the magnetic properties of tissue. Thus, the detection of blood residues and calcifications in SWI is superior to conventional MR sequences. FUTURE PROSPECTS: New techniques, such as quantitative susceptibility mapping (QSM) and susceptibility tensor imaging (STI) allow improved differentiation between blood residues and calcifications and provide an alternative imaging method for fiber tractography with respect to diffusion tensor imaging.