Image quality of opportunistic breast examinations in photon-counting computed tomography: A phantom study.

PURPOSE: To compare the breast imaging performance of a clinical whole-body photon-counting CT (PCCT) to that of a dedicated breast CT (BCT) to determine the image quality of opportunistic breast examinations in clinical PCCT. MATERIALS AND METHODS: To quantify image quality for breast cancer applications, acquisitions of a breast phantom including representations of calcifications, fibers, and masses were performed using a clinical PCCT and a dedicated BCT. When imaging with the PCCT, the phantom was also combined with a thorax phantom to simulate realistic patient positioning, while only the breast phantom was imaged in the BCT. Images in BCT were acquired at 7.0 mGy (CTDI16cm) and using 2.6 mGy-25.0 mGy in the PCCT. Spatial resolution between the BCT and PCCT images was matched and data were reconstructed using the default methods of each system. The dose-normalized contrast-to-noise ratio (CNRD) of masses and the structural visibility of fibers and calcifications were evaluated as figures of merit for all reconstructions. RESULTS: CNRD between masses and background was 0.56 mGy-½, on average with BCT and varied between 0.39 mGy-½ to 1.46 mGy-½ with PCCT over all dose levels, phantom configurations, and reconstruction algorithms. Calcifications down to a size of 0.29 mm and fibers down to a size of 0.23 mm could be reliably identified in the images of both systems. CONCLUSIONS: Clinical PCCT provides an image quality superior to that obtained with BCT in terms of CNRD and allows for the identification of calcifications and fibers at comparable dose levels.

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.

The effect of hemodynamic parameters in patient-based coronary artery models with serial stenoses: normal and hypertension cases.

The purpose of this study is to investigate the hemodynamic significance of various degrees of coronary area of stenosis (AS) and multiple sequential stenoses (MSS) in normal and hypertension pressure conditions. MSS in a single branch coronary artery pose challenges to determine the physiological assessment in the prevalent invasive intervention. The hemodynamic parameters of each stenosis are influenced by other stenoses in the single branch of MSS coronary artery. In this study, we entirely use open source tools and techniques for coronary computed tomography angiography (CCTA) image segmentation, 3D reconstruction, grid generation and hemodynamic simulations. The results yield different hemodynamic parameters such as velocity magnitude, mean arterial pressure difference, flow-pressure linear relation, wall shear stress (WSS) and eventually virtual fractional flow reserve (vFFR) allowing for the prediction and the assessment of lumen area severity conditions in MSS coronaries.

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.

Correction: Role of growth arrest-specific gene 6-mer axis in multiple myeloma.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Role of Growth arrest-specific gene 6-Mer axis in multiple myeloma.

Multiple myeloma is a mostly incurable malignancy characterized by the expansion of a malignant plasma cell (PC) clone in the human bone marrow (BM). Myeloma cells closely interact with the BM stroma, which secretes soluble factors that foster myeloma progression and therapy resistance. Growth arrest-specific gene 6 (Gas6) is produced by BM-derived stroma cells and can promote malignancy. However, the role of Gas6 and its receptors Axl, Tyro3 and Mer (TAM receptors) in myeloma is unknown. We therefore investigated their expression in myeloma cell lines and in the BM of myeloma patients and healthy donors. Gas6 showed increased expression in sorted BMPCs of myeloma patients compared with healthy controls. The fraction of Mer(+) BMPCs was increased in myeloma patients in comparison with healthy controls whereas Axl and Tyro3 were not expressed by BMPCs in the majority of patients. Downregulation of Gas6 and Mer inhibited the proliferation of different myeloma cell lines, whereas knocking down Axl or Tyro3 had no effect. Inhibition of the Gas6 receptor Mer or therapeutic targeting of Gas6 by warfarin reduced myeloma burden and improved survival in a systemic model of myeloma. Thus, the Gas6-Mer axis represents a novel candidate for therapeutic intervention in this incurable malignancy.

The retrobulbar sinus is superior to the lateral tail vein for the injection of contrast media in small animal cardiac imaging.

Cardiac perfusion studies using computed tomography are a common tool in clinical practice. Recent technical advances and the availability of dedicated small animal scanners allow the transfer of these techniques to the preclinical sector in general and to mouse models of cardiac diseases in particular. This necessitates new requirements for contrast injection techniques as a rapid transport of contrast media from the intravenous access to the animal heart. Clinical contrast agents containing high iodine concentrations are used within small animal studies although they exhibit a high viscosity which might limit their transport within the vasculature. The authors provide a comparison of the transport of contrast media following an injection into the lateral tail vein and an injection into the retrobulbar sinus and discuss the anatomy involved. The temporal evolution of a contrast bolus and its in vivo distribution is visualized. It is demonstrated that injecting contrast agents into the lateral tail vein of mice results in a retrograde blood flow to the liver veins and therefore does not deliver a detectable contrast bolus to the heart, and thus it cannot be used for cardiac perfusion studies. By contrast, boli injected into the retrobulbar sinus are rapidly transported to the heart and provide ventricular contrast enabling perfusion studies similar to those in human patients. The results demonstrate that an injection into the retrobulbar sinus is superior to an injection into the lateral tail vein for the delivery of contrast boli to the animal heart, while all drawbacks of an injection into the lateral tail vein are overcome.

Armed and targeted measles virus for chemovirotherapy of pancreatic cancer.

No curative therapy is currently available for locally advanced or metastatic pancreatic cancer. Therefore, new therapeutic approaches must be considered. Measles virus (MV) vaccine strains have shown promising oncolytic activity against a variety of tumor entities. For specific therapy of pancreatic cancer, we generated a fully retargeted MV that enters cells exclusively through the prostate stem cell antigen (PSCA). Besides a high-membrane frequency on prostate cancer cells, this antigen is expressed on pancreatic adenocarcinoma, but not on non-neoplastic tissue. PSCA expression levels differ within heterogeneous tumor bulks and between human pancreatic cell lines, and we could show specific infection of pancreatic adenocarcinoma cell lines with both high- and low-level PSCA expression. Furthermore, we generated a fully retargeted and armed MV-PNP-anti-PSCA to express the prodrug convertase purine nucleoside phosphorylase (PNP). PNP, which activates the prodrug fludarabine effectively, enhanced the oncolytic efficacy of the virus on infected and bystander cells. Beneficial therapeutic effects were shown in a pancreatic cancer xenograft model. Moreover, in the treatment of gemcitabine-resistant pancreatic adenocarcinoma cells, no cross-resistance to both MV oncolysis and activated prodrug was detected.

Temporary warm ischaemia, 5/6 nephrectomy and single uranyl nitrate administration--comparison of three models intended to cause renal fibrosis in rats.

In patients the progression of pathologic renal processes after the treatment of primary disease is a problem of increasing importance and therapeutic strategies are insufficient till now. The aim of this paper was to search for rat models of interstitial fibrosis as a basis for testing therapeutic strategies to prevent end-stage renal failure. Experiments were done on adult female Wistar rats (Han:Wist) to investigate long-term consequences of temporary warm ischaemia, 5/6 nephrectomy (5/6 NX) and single uranyl nitrate (UN) administration (0.3 or 0.5 mg/ 100 g body wt. intraperitoneally). Observation time was 20 weeks after injury in each group. Creatinine clearance, urinary protein excretion and hydroxy-proline (OH-proline) concentration in renal tissue were measured and light microscopic investigations were done to characterise both quality and time course of long-term renal damage in relation to matched control animals. Temporary warm ischaemia and 5/6 NX did not cause any fibrotic changes during the 20 weeks observation period. The higher UN dose led to decreased creatinine clearance, increased urinary protein excretion and enhanced OH-proline concentration in renal tissue. Morphologic investigations showed fibrotic areas containing strongly dilated and atrophic tubules with thickened basal membranes. These effects can be seen from week four after UN administration up to the end of the observation period. In conclusion, administration of one single dose of UN is a simple procedure to induce interstitial renal fibrosis as an experimental model to investigate therapeutic strategies for their prevention.

Cell-mediated and humoral immune responses in guinea pigs sensitized with the thermostable antigen of human granulocytes (TSGA).

Cell-mediated and humoral immune responses are induced shortly after a single injection of the human thermostable granulocyte antigen TSGA to guinea pigs. This was proved by means of the lymphocyte transformation assay and the estimation of MIF and LIF activity in supernatants of antigen-stimulated lymph node cells as well as by immunodiffusion, immunoelectrophoresis and immunohistology. The maximum of the cellular response was observed 10 days after immunization. The antibody production appeared after a lag time and increased continuously thereafter. The antisera of guinea pig yields a strong specific fluorescence in neutrophils and a weak fluorescence in monocytes of man. The humoral immune responses of guinea pig antisera correspond to the results obtained with antisera from rabbits.