COVID-19 and Body Iron: A Survey on Phenomenological and Genetic Correlations.

To provide solid information about viral infection, disease, and body iron metabolism, the literature was surveyed for mutual correlations. Gender and age profiles of COVID-19 infection and disease correlate well with the profiles of serum iron and ferritin with correlation coefficients ≥ 0.75. There are further symptomatic hints that the ABO blood group system contributes to these correlations. Remarkably, the susceptibility to both the viral disease and iron dyshomeostasis can be traced back to the same gene loci of the ABO blood group system. The overlapping of susceptible gene loci together with the phenomenological correlations in gender and age are strong indicators for the interrelation of body iron dyshomeostasis with COVID-19 infection and disease.

DCE-MR imaging of orbital lesions: diagnostic performance of the tumor flow residence time τ calculated by a multi-compartmental pharmacokinetic tumor model based on individual factors.

BACKGROUND: Differentiating benign from malignant orbital lesions by imaging and clinical presentation can be challenging. PURPOSE: To differentiate benign from malignant orbital masses using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) based on tumor flow residence time τ calculated with the aid of a pharmacokinetic tumor model. MATERIAL AND METHODS: Sixty patients with orbital masses were investigated by 3-T MRI including dynamic sequences. The signal intensity-time curve after i.v. contrast medium administration within lesions was approximated by Gd-concentration profiles on the basis of model calculations where the tumor is embedded in a whole-body kinetic model. One output of the model was tumor flow residence time τ, defined as the ratio of the tumor volume and the tumor blood flow rate. Receiver operating characteristic (ROC) curves were used to analyze the diagnostic performance of τ. The results were compared with those of Ktrans, kep, ve, iAUC, and ADC. RESULTS: Thirty-one benign and 29 malignant orbital masses were identified (reference standard: histopathology, clinical characteristics). Mean τ was significantly longer for benign masses (94 ± 48 s) than for malignant masses (21 ± 19 s, P < 0.001). ROC analysis revealed the highest area under the curve (AUC = 0.94) for τ in orbital masses compared to standard methods. CONCLUSION: Tumor flow residence times τ of benign and malignant orbital masses are valuable in the diagnostic work-up of orbital tumors. Measures of diagnostic accuracy were superior for τ compared to ADC, Ktrans, ve, and iAUC.

Contrast Media for X-ray and Magnetic Resonance Imaging: Development, Current Status and Future Perspectives.

Over the last 120 years, the extensive advances in medical imaging allowed enhanced diagnosis and therapy of many diseases and thereby improved the quality of life of many patient generations. From the beginning, all technical solutions and imaging procedures were combined with dedicated pharmaceutical developments of contrast media, to further enhance the visualization of morphology and physiology. This symbiosis of imaging hardware and contrast media development was of high importance for the development of modern clinical radiology. Today, all available clinically approved contrast media fulfill the highest requirements for clinical safety and efficacy. All new concepts to increase the efficacy of contrast media have also to consider the high clinical safety standards and cost of goods of current marketed contrast media. Nevertheless, diagnostic imaging will contribute significantly to the progresses in medicine, and new contrast media developments are mandatory to address the medical needs of the future.

Correlation of contrast agent kinetics between iodinated contrast-enhanced spectral tomosynthesis and gadolinium-enhanced MRI of breast lesions.

OBJECTIVES: Assessment of contrast agent kinetics in contrast-enhanced MRI (CE-MRI) with gadolinium-containing contrast agents offers the opportunity to predict breast lesion malignancy. The goal of our study was to determine if similar patterns exist for spectral contrast-enhanced digital breast tomosynthesis (CE-DBT) using an iodinated contrast agent. METHODS: The protocol of our prospective study was approved by the relevant institutional review board and the German Federal Office for Radiation Protection. All patients provided written informed consent. We included 21 women with a mean age of 62.4 years. All underwent ultrasound-guided biopsy of a suspect breast lesion, spectral CE-DBT and CE-MRI. For every breast lesion, contrast agent kinetics was assessed by signal intensity-time curves for spectral CE-DBT and CE-MRI. Statistical comparison used Cohen's kappa and Spearman's rho test. RESULTS: Spearman's rho of 0.49 showed significant (P = 0.036) correlation regarding the contrast agent kinetics in signal intensity-time curves for spectral CE-DBT and CE-MRI. Cohen's kappa indicated moderate agreement (kappa = 0.438). CONCLUSION: There is a statistically significant correlation between contrast agent kinetics in the signal intensity-time curves for spectral CE-DBT and CE-MRI. Observing intralesional contrast agent kinetics in spectral CE-DBT may aid evaluation of malignant breast lesions. KEY POINTS: • Contrast agent kinetics can be assessed using spectral digital breast tomosynthesis (DBT). • Contrast agent kinetics patterns in spectral DBT are similar to those in contrast-enhanced MRI. • Multiple contrast enhancement for spectral DBT gives additional diagnostic information.

Pharmacokinetic approach for dynamic breast MRI to indicate signal intensity time curves of benign and malignant lesions by using the tumor flow residence time.

OBJECTIVE: The objective of this study was to evaluate a novel pharmacokinetic approach integrating a tumor model in a whole-body pharmacokinetic model to simulate contrast media-induced signal intensity time curves of breast tumors on dynamic contrast-enhanced magnetic resonance mammography. MATERIALS AND METHODS: A recently developed, whole-body pharmacokinetic model, which describes the distribution and excretion of renally discharged contrast media, has been expanded by integrating a tumor model. The parameters of the general approach including exchange between plasma and interstitium were set as fixed values; only 2 tumor-specific parameters, blood volume fraction Vblood and blood flow kt, were varied. These parameters were adjusted with regard to signal intensity time course data of histologically verified benign and malignant mass-like breast lesions on clinical magnetic resonance imaging examinations (1.5 T) using 2 different contrast media (gadopentetate dimeglumine and gadoterate meglumine) and 2 application doses (0.1 and 0.2 mmol kg body weight). Thus, measured signal intensity time curves were compared with simulated gadolinium (Gd) concentration time curves calculated by the pharmacokinetic model. RESULTS: Benign lesions showed continuous signal increase; malignant tumors presented fast initial signal increase followed by washout effect. According to the pharmacokinetic approach, the variation of the Vblood/kt ratio, which defined the tumor flow residence time τr, led to Gd concentration time curves congruent with the shapes of the measured signal intensity time curves. Low values of τr were characteristic for malignant tumors, and high values were typical for benign lesions; τr of 200 seconds best separated malignant from benign tumors. Thus, the dynamic magnetic resonance imaging data can be well approximated by the pharmacokinetic model considering 2 contrast media and application doses. The calculated Gd concentration time curves of 0.1 mmol kg body weight gadopentetate dimeglumine and gadoterate meglumine overlapped for benign lesions; the curve of gadoterate meglumine was by a factor of 0.8 below the curve of gadopentetate dimeglumine for malignant tumors. Doubling the application dose of gadopentetate dimeglumine from 0.1 to 0.2 mmol kg led to an increase in the Gd concentration time curves for benign lesions but not for malignant tumors. High Gd concentrations with values greater than 1 mmol L were calculated in the vessels of the malignant tumors, outside the determined range of the linear relationship between Gd concentration and signal intensity due to saturation effects. CONCLUSIONS: On the basis of this pharmacokinetic model, the contrast media-induced time curves on dynamic contrast-enhanced magnetic resonance mammography can be classified by a single kinetic parameter, the tumor flow residence time τr, into benign (τr >200 seconds) and malignant (τr <200 seconds) curve shapes. Possible clinical application of this model is to create pharmacokinetic maps, displaying tumor flow residence times, for computer-assisted diagnosis, which may be integrated into clinical routine for the diagnosis of breast lesions.

Pharmacokinetics of contrast media in humans: model with circulation, distribution, and renal excretion.

AIM: : To contribute to the understanding of the pharmacokinetics of intravenously administered, renally excreted contrast media with circulation, distribution, and renal excretion providing access to optimized and patient-based administration protocols. METHOD: : Numerical solutions of the pharmacokinetic equations are presented where the physiological parameters (organ volumes, blood flows) and administration parameters (dose, concentration, and velocity) are fixed and the variable parameters (the exchange rates between plasma and interstitium, the rate for renal excretion) are adjusted to results from clinical studies of healthy individuals. RESULTS: : Recirculation, organ plasma concentrations, and renal excretion are adequately modeled. With the calculated distribution and renal excretion rates, 3 time periods are discriminated: CONCLUSION: : The model describes bolus tracking, recirculation, plasma to interstitium distribution, and renal excretion. For known administration parameters, the relevant pharmacokinetic parameters can be achieved from the results of clinical studies. If the arguments are reversed, the pharmacokinetic parameters obtained allow the calculation of personalized administration protocols for computed tomography and magnetic resonance imaging examinations where the 2 initial time periods are essential.

Development of low-dose photon-counting contrast-enhanced tomosynthesis with spectral imaging.

PURPOSE: To demonstrate the feasibility of low-dose photon-counting tomosynthesis in combination with a contrast agent (contrast material-enhanced tomographic mammography) for the differentiation of breast cancer. MATERIALS AND METHODS: All studies were approved by the institutional review board, and all patients provided written informed consent. A phantom model with wells of iodinated contrast material (3 mg of iodine per milliliter) 1, 2, 5, 10, and 15 mm in diameter was assessed. Nine patients with malignant lesions and one with a high-risk lesion (atypical papilloma) were included (all women; mean age, 60.7 years). A multislit photon-counting tomosynthesis system was utilized (spectral imaging) to produce both low- and high-energy tomographic data (below and above the k edge of iodine, respectively) in a single scan, which allowed for dual-energy visualization of iodine. Images were obtained prior to contrast material administration and 120 and 480 seconds after contrast material administration. Four readers independently assessed the images along with conventional mammograms, ultrasonographic images, and magnetic resonance images. Glandular dose was estimated. RESULTS: Contrast agent was visible in the phantom model with simulated spherical tumor diameters as small as 5 mm. The average glandular dose was measured as 0.42 mGy per complete spectral imaging tomosynthesis scan of one breast. Because there were three time points (prior to contrast medium administration and 120 and 480 seconds after contrast medium administration), this resulted in a total dose of 1.26 mGy for the whole procedure in the breast with the abnormality. Seven of 10 cases were categorized as Breast Imaging Reporting and Data System score of 4 or higher by all four readers when reviewing spectral images in combination with mammograms. One lesion near the chest wall was not captured on the spectral image because of a positioning problem. CONCLUSION: The use of contrast-enhanced tomographic mammography has been demonstrated successfully in patients with promising diagnostic benefit. Further studies are necessary to fully assess diagnostic sensitivity and specificity.

Photoelectric-enhanced radiation therapy with quasi-monochromatic computed tomography.

Photoelectric-enhanced radiation therapy is a bimodal therapy, consisting of the administration of highly radiation-absorbing substances into the tumor area and localized regional irradiation with orthovoltage x-rays. Irradiation can be performed by a modified computed tomography (CT) unit equipped with an additional x-ray optical module which converts the polychromatic, fan-shaped CT beam into a monochromatized and focused beam for energy-tuned photoelectric-enhanced radiotherapy. A dedicated x-ray optical module designed for spatial collimation, focusing, and monochromatization was mounted at the exit of the x-ray tube of a clinical CT unit. Spectrally resolved measurements of the resulting beam were performed using an energy-dispersive detection system calibrated by synchrotron radiation. The spatial photon fluence was determined by film dosimetry. Depth-dose measurements were performed and compared to the polychromatic CT and a therapeutic 6 MV beam. The spatial dose distribution in phantoms using a rotating radiation source (quasimonochromatic CT and 6 MV, respectively) was investigated by gel dosimetry. The photoelectric dose enhancement for an iodine fraction of 1% in tissue was calculated and verified experimentally. The x-ray optical module selectively filters the energy of the tungsten Kalpha emission line with an FWHM of 5 keV. The relative photon fluence distribution demonstrates the focusing characteristic of the x-ray optical module. A beam width of about 3 mm was determined at the isocenter of the CT gantry. The depth-dose measurements resulted in a half-depth value of approximately 36 mm for the CT beams (quasi-monochromatic, polychromatic) compared to 154 mm for the 6 MV beam. The rotation of the radiation source leads to a steep dose gradient at the center of rotation; the gel dosimetry yields an entrance-to-peak dose ratio of 1:10.8 for the quasi-monochromatic CT and 1:37.3 for a 6 MV beam of the same size. The photoelectric dose enhancement factor increases from 2.2 to 2.4 by using quasi-monochromatic instead of polychromatic radiation. An additional increase in the radiation dose by a factor of 1.4 due to the focusing characteristic of the x-ray optical module was calculated. Photoelectric-enhanced radiation therapy based on a clinical CT unit combined with an x-ray optical module is a novel therapy option in radiation oncology. The optimized quasi-monochromatic radiation is strongly focused and ensures high photoelectric dose enhancement for iodine.

Novel approach in radionuclide tumor therapy: dose enhancement by high Z-element contrast agents.

PURPOSE: The aim of this study was to first calculate the dose-enhancement effect from internalized radiation by the presence of exogenous contrast media using Monte Carlo simulations, and then provide in vitro proof-of-concept for this novel method of radiation-dose enhancement. MATERIALS AND METHODS: The Monte Carlo program EGSnrc (Electron Gamma Shower) was used to simulate the interaction of internalizing radiation with iodine (I) or gadolinium (Gd) containing contrast media. Experimentally, the doseenhancement effect induced by I or Gd was evaluated in cell culture assays using internalizing peptides chelated with beta- emitting radionuclides and clinically available contrast media. RESULTS: Monte Carlo simulations predicted significant enhancement (approximately 70-340%) of radiation dose in the presence of high Zelement contrast media. This enhancement is radiation and Z-element dependent. Calculations showed that in the presence of contrast media, low-energy radionuclides favor localization of secondary particles, whereas higher energy beta- emitters localize radiation by reducing the pathway of the primary beta-particle. The dose enhancement was verified in vitro in two cell lines. CONCLUSIONS: Monte Carlo simulations in parallel with in vitro studies provide proof-of-principle for dose enhancement that occurs when utilizing an internalized source of radiation followed by the addition of exogenous contrast media. This dose enhancement is both radiation and Z-element dependent.

Monochromatic x-rays in digital mammography.

RATIONALE AND BACKGROUND: The emission spectrum of an x-ray tube is determined by the anode and filter materials as well as by the high voltage being used. For mammography, typical anode materials are molybdenum (Mo), rhodium (Rh), and tungsten (W); molybdenum, rhodium, and aluminum are favored for filters. Mammography is a soft tissue imaging modality demanding a high spatial resolution as well as a high detector sensitivity. Low-energy photons are only absorbed in tissue and have no contribution to the image; nevertheless, they increase the dose. High-energy photons mostly penetrate soft tissue and generate a background noise as a result of strong scattering that deteriorates the image quality. For mammography, the optimal energy window is in a range from 17 and 25 keV. From a theoretical perspective, one would favor monoenergetic x-rays (eg, the Mo-emission line at 17.5 keV). This article presents the realization of imaging with monochromatic x-rays using a diagnostic mammography unit. METHODS: Basically, a monochromatic module was added to a conventional mammographic system. The monochromatic module can be mounted at the end of the x-ray tube and it consists of a curved HOPG (highly oriented pyrolytic graphite) crystal and a slit collimator. For image generation, the object is moved through the fan-shaped monochromatic radiation field. In addition to the conventional polychromatic 2-dimensional case, the polychromatic irradiation was also able to be performed under similar conditions. For image acquisition, image plates or a linear array detector were used. Exposure doses were measured for both poly- and monochromatic radiation. The initial evaluation of the system performance was carried out by imaging a contrast-detail phantom and biologic specimens. RESULTS: The monochromatic x-ray beam has a size of approximately 35 mm x 200 mm in the object plane. The photon flux of the monochromatic x-rays is considerably lower than the photon flux of the polychromatic x-rays but adequate for initial studies of phantoms, biologic tissue, or small animals. The comparison of the results obtained with the monochromatic and polychromatic imaging modalities reveal a conspicuous increase of image contrast in the monochromatic case. CONCLUSION: The results suggest that the experimental setup for monochromatic excitation shows clear potentials for improvements of the image in comparison to the conventional polychromatic case.

New contrast media designed for x-ray energy subtraction imaging in digital mammography.

RATIONALE AND OBJECTIVES: In contrast-enhanced dual-energy subtraction imaging 2 images acquired postcontrast media administration at different energies are subtracted to highlight structures hidden in the absence of contrast media. X-ray spectra of the newly developed digital full-field mammography units (GE Senographe 2000 D) are dominated by the emission lines of the Mo or Rh anodes. The K-edge of Zirconium (Zr) is flanked by these 2 emission lines. Thus, the attenuation of Zr should experience a pronounced change of attenuation in parallel with a change of anodes. Under clinically relevant conditions, the contrasting behavior of Zr should be compared with that of other elements having K-edge energies outside the window spanned by the 2 anode emission lines. METHODS: Solutions containing the contrasting elements Br, Y, Zr, I, and Gd were investigated for dual-energy subtraction in digital mammography with the 2 anode/filter settings (Mo/Mo and Rh/Rh). These solutions were investigated in phantom studies in the energy range conventionally used in mammography. Additionally, the contrasting behavior of Zr and I was compared in an in vivo study in rats. RESULTS: The sweeping over the K-edge by alternating between the Mo and Rh anodes increases the detection of Zr in energy subtraction imaging at constant high voltage. This procedure does not lead to sufficient contrast enhancement for iodine-based contrast media which become detectable by increasing the high voltage to 40-49 kV. CONCLUSION: The instrumental and physical data outlined predestine Zr as contrasting element with a high potential for energy subtraction imaging in digital mammography in the energy range conventionally applied.