Correction for Mechanical Inaccuracies in a Scanning Talbot-Lau Interferometer.

Grating-based X-ray phase-contrast and in particular dark-field radiography are promising new imaging modalities for medical applications. Currently, the potential advantage of dark-field imaging in early-stage diagnosis of pulmonary diseases in humans is being investigated. These studies make use of a comparatively large scanning interferometer at short acquisition times, which comes at the expense of a significantly reduced mechanical stability as compared to tabletop laboratory setups. Vibrations create random fluctuations of the grating alignment, causing artifacts in the resulting images. Here, we describe a novel maximum likelihood method for estimating this motion, thereby preventing these artifacts. It is tailored to scanning setups and does not require any sample-free areas. Unlike any previously described method, it accounts for motion in between as well as during exposures.

CT-Guided Liver Biopsy: Evaluation of Spectral Data From Dual-Layer Detector CT for Improved Lesion Detection.

PURPOSE: Evaluation of dual-layer spectral computed tomography (CT) for contrast enhancement during image-guided biopsy of liver lesions using virtual monoenergetic images (VMI) and virtual non-contrast (VNC) images. METHODS: Spectral CT data of 20 patients receiving CT-guided needle biopsy of focal liver lesions were used to generate VMI at energy levels from 40 to 200 keV and VNC images. Images were analyzed objectively regarding contrast-to-noise ratio between lesion center (CNRcent) or periphery (CNRperi) and normal liver parenchyma. Lesion visibility and image quality were evaluated on a 4-point Likert scale by two radiologists. RESULTS: Using VMI/VNC images, readers reported an increased visibility of the lesion compared to the conventional CT images in 18/20 cases. In 75% of cases, the highest visibility was derived by VMI-40. Showing all reconstructions simultaneously, VMI-40 offered the highest visibility in 75% of cases, followed by VNC in 12.5% of cases. Either CNRcent (17/20) or/and CNRperi (17/20) was higher (CNR increase > 50%) in 19/20 cases for VMI-40 or VNC images compared to conventional CT images. VMI-40 showed the highest CNRcent in 14 cases and the highest CNRperi in 12 cases. High image quality was present for all reconstructions with a minimum median of 3.5 for VMI-40 and VMI-50. CONCLUSIONS: When implemented in the CT scanner software, automated contrast enhancement of liver lesions during image-guided biopsy may facilitate the procedure.

Dark-field chest x-ray imaging: first experience in patients with alpha1-antitrypsin deficiency.

BACKGROUND: Spirometry and conventional chest x-ray have limitations in investigating early emphysema, while computed tomography, the reference imaging method in this context, is not part of routine patient care due to its higher radiation dose. In this work, we investigated a novel low-dose imaging modality, dark-field chest x-ray, for the evaluation of emphysema in patients with alpha1-antitrypsin deficiency. METHODS: By exploiting wave properties of x-rays for contrast formation, dark-field chest x-ray visualises the structural integrity of the alveoli, represented by a high signal over the lungs in the dark-field image. We investigated four patients with alpha1-antitrypsin deficiency with a novel dark-field x-ray prototype and simultaneous conventional chest x-ray. The extent of pulmonary function impairment was assessed by pulmonary function measurement and regional emphysema distribution was compared with CT in one patient. RESULTS: We show that dark-field chest x-ray visualises the extent of pulmonary emphysema displaying severity and regional differences. Areas with low dark-field signal correlate with emphysematous changes detected by computed tomography using a threshold of -950 Hounsfield units. The airway parameters obtained by whole-body plethysmography and single breath diffusing capacity of the lungs for carbon monoxide demonstrated typical changes of advanced emphysema. CONCLUSIONS: Dark-field chest x-ray directly visualised the severity and regional distribution of pulmonary emphysema compared to conventional chest x-ray in patients with alpha1-antitrypsin deficiency. Due to the ultra-low radiation dose in comparison to computed tomography, dark-field chest x-ray could be beneficial for long-term follow-up in these patients.

Image processing improvements afford second-generation handheld optoacoustic imaging of breast cancer patients.

Background: Since the initial breast transillumination almost a century ago, breast cancer imaging using light has been considered in different implementations aiming to improve diagnostics, minimize the number of available biopsies, or monitor treatment. However, due to strong photon scattering, conventional optical imaging yields low resolution images, challenging quantification and interpretation. Optoacoustic imaging addresses the scattering limitation and yields high-resolution visualization of optical contrast, offering great potential value for breast cancer imaging. Nevertheless, the image quality of experimental systems remains limited due to a number of factors, including signal attenuation with depth and partial view angle and motion effects, particularly in multi-wavelength measurements. Methods: We developed data analytics methods to improve the accuracy of handheld optoacoustic breast cancer imaging, yielding second-generation optoacoustic imaging performance operating in tandem with ultrasonography. Results: We produced the most advanced images yet with handheld optoacoustic examinations of the human breast and breast cancer, in terms of resolution and contrast. Using these advances, we examined optoacoustic markers of malignancy, including vasculature abnormalities, hypoxia, and inflammation, on images obtained from breast cancer patients. Conclusions: We achieved a new level of quality for optoacoustic images from a handheld examination of the human breast, advancing the diagnostic and theranostic potential of the hybrid optoacoustic-ultrasound (OPUS) examination over routine ultrasonography.

X-ray Dark-Field CT for Early Detection of Radiation-induced Lung Injury in a Murine Model.

Online supplemental material is available for this article.

A randomized trial of risk-adapted screening for prostate cancer in young men-Results of the first screening round of the PROBASE trial.

There is no generally accepted screening strategy for prostate cancer (PCa). From February 2014 to December 2019 a randomized trial (PROBASE) recruited 46 642 men at age 45 to determine the efficacy of risk-adapted prostate-specific antigen-based (PSA) screening, starting at either 45 or 50 years. PSA tests are used to classify participants into a low (<1.5 ng/mL), intermediate (1.5-2.99 ng/mL) or high (≥3 ng/mL) risk group. In cases of confirmed PSA values ≥3 ng/mL participants are recommended a prostate biopsy with multiparametric magnetic resonance imaging (mpMRI). Half of the participants (N = 23 341) were offered PSA screening immediately at age 45; the other half (N = 23 301) were offered digital rectal examination (DRE) with delayed PSA screening at age 50. Of 23 301 participants who accepted baseline PSA testing in the immediate screening arm, 89.2% fell into the low, 9.3% into intermediate, and 1.5% (N = 344) into the high risk group. Repeat PSA measurement confirmed high-risk status for 186 men (0.8%), of whom 120 (64.5%) underwent a biopsy. A total of 48 PCas was detected (overall prevalence 0.2%), of which 15 had International Society of Uropathology (ISUP) grade 1, 29 had ISUP 2 and only 4 had ISUP ≥3 cancers. In the delayed screening arm, 23 194 participants were enrolled and 6537 underwent a DRE with 57 suspicious findings, two of which showed PCa (both ISUP 1; detection rate 0.03%). In conclusion, the prevalence of screen-detected aggressive (ISUP ≥3) PCa in 45-year-old men is very low. DRE did not turn out effective for early detection of PCa.

X-ray dark-field chest imaging for detection and quantification of emphysema in patients with chronic obstructive pulmonary disease: a diagnostic accuracy study.

BACKGROUND: Although advanced medical imaging technologies give detailed diagnostic information, a low-dose, fast, and inexpensive option for early detection of respiratory diseases and follow-ups is still lacking. The novel method of x-ray dark-field chest imaging might fill this gap but has not yet been studied in living humans. Enabling the assessment of microstructural changes in lung parenchyma, this technique presents a more sensitive alternative to conventional chest x-rays, and yet requires only a fraction of the dose applied in CT. We studied the application of this technique to assess pulmonary emphysema in patients with chronic obstructive pulmonary disease (COPD). METHODS: In this diagnostic accuracy study, we designed and built a novel dark-field chest x-ray system (Technical University of Munich, Munich, Germany)-which is also capable of simultaneously acquiring a conventional thorax radiograph (7 s, 0·035 mSv effective dose). Patients who had undergone a medically indicated chest CT were recruited from the department of Radiology and Pneumology of our site (Klinikum rechts der Isar, Technical University of Munich, Munich, Germany). Patients with pulmonary pathologies, or conditions other than COPD, that might influence lung parenchyma were excluded. For patients with different disease stages of pulmonary emphysema, x-ray dark-field images and CT images were acquired and visually assessed by five readers. Pulmonary function tests (spirometry and body plethysmography) were performed for every patient and for a subgroup of patients the measurement of diffusion capacity was performed. Individual patient datasets were statistically evaluated using correlation testing, rank-based analysis of variance, and pair-wise post-hoc comparison. FINDINGS: Between October, 2018 and December, 2019 we enrolled 77 patients. Compared with CT-based parameters (quantitative emphysema ρ=-0·27, p=0·089 and visual emphysema ρ=-0·45, p=0·0028), the dark-field signal (ρ=0·62, p<0·0001) yields a stronger correlation with lung diffusion capacity in the evaluated cohort. Emphysema assessment based on dark-field chest x-ray features yields consistent conclusions with findings from visual CT image interpretation and shows improved diagnostic performance than conventional clinical tests characterising emphysema. Pair-wise comparison of corresponding test parameters between adjacent visual emphysema severity groups (CT-based, reference standard) showed higher effect sizes. The mean effect size over the group comparisons (absent-trace, trace-mild, mild-moderate, and moderate-confluent or advanced destructive visual emphysema grades) for the COPD assessment test score is 0·21, for forced expiratory volume in 1 s (FEV1)/functional vital capacity is 0·25, for FEV1% of predicted is 0·23, for residual volume % of predicted is 0·24, for CT emphysema index is 0·35, for dark-field signal homogeneity within lungs is 0·38, for dark-field signal texture within lungs is 0·38, and for dark-field-based emphysema severity is 0·42. INTERPRETATION: X-ray dark-field chest imaging allows the diagnosis of pulmonary emphysema in patients with COPD because this technique provides relevant information representing the structural condition of lung parenchyma. This technique might offer a low radiation dose alternative to CT in COPD and potentially other lung disorders. FUNDING: European Research Council, Deutsche Forschungsgemeinschaft, Royal Philips, and Karlsruhe Nano Micro Facility.

In-vivo X-ray dark-field computed tomography for the detection of radiation-induced lung damage in mice.

BACKGROUND AND PURPOSE: Radiotherapy of thoracic tumours can lead to side effects in the lung, which may benefit from early diagnosis. We investigated the potential of X-ray dark-field computed tomography by a proof-of-principle murine study in a clinically relevant radiotherapeutic setting aiming at the detection of radiation-induced lung damage. MATERIAL AND METHODS: Six mice were irradiated with 20 Gy to the entire right lung. Together with five unirradiated control mice, they were imaged using computed tomography with absorption and dark-field contrast before and 16 weeks post irradiation. Mean pixel values for the right and left lung were calculated for both contrasts, and the right-to-left-ratio R of these means was compared. Radiologists also assessed the tomograms acquired 16 weeks post irradiation. Sensitivity, specificity, inter- and intra-reader accuracy were evaluated. RESULTS: In absorption contrast the group-average of R showed no increase in the control group and increased by 7% (p = 0.005) in the irradiated group. In dark-field contrast, it increased by 2% in the control group and by 14% (p = 0.005) in the irradiated group. Specificity was 100% for both contrasts but sensitivity was almost four times higher using dark-field tomography. Two cases were missed by absorption tomography but were detected by dark-field tomography. CONCLUSIONS: The applicability of X-ray dark-field computed tomography for the detection of radiation-induced lung damage was demonstrated in a pre-clinical mouse model. The presented results illustrate the differences between dark-field and absorption contrast and show that dark-field tomography could be advantageous in future clinical settings.

Dosimetry on first clinical dark-field chest radiography.

PURPOSE: The purpose of this study was to evaluate the dose characteristic for patient examinations at the first clinical X-ray dark-field chest radiography system and to determine whether the effective patient dose is within a clinically acceptable dose range. METHODS: A clinical setup for grating-based dark-field chest radiography was constructed and commissioned, operating at a tube voltage of 70 kVp. Thermoluminescent dosimeter (TLD) measurements were conducted using an anthropomorphic phantom modeling the reference person to obtain a conversion coefficient relating dose area product (DAP) to effective patient dose at the dark-field system. For 92 patients, the DAP values for posterior-anterior measurements were collected at the dark-field system. Using the previously determined conversion coefficient, the effective dose was calculated. RESULTS: A reference person, modeled by an anthropomorphic phantom, receives an effective dose of 35 µSv. For the examined patients, a mean effective dose of 39 µSv was found. CONCLUSIONS: The effective dose at the clinical dark-field radiography system, generating both attenuation and dark-field images, is within the range of reported standard dose values for chest radiography.

Improved differentiation between primary lung cancer and pulmonary metastasis by combining dual-energy CT-derived biomarkers with conventional CT attenuation.

OBJECTIVES: To assess the clinical utility of dual-energy CT (DE-CT)-derived iodine concentration (IC) and effective Z (Zeff) in addition to conventional CT attenuation (HU) for the discrimination between primary lung cancer (LC) and pulmonary metastases (PM) from different primary malignancies. METHODS: DE-CT scans of 79 patients with LC (3 histopathologic subgroups) and 89 patients with PM (5 histopathologic subgroups) were evaluated. Quantitative IC, Zeff, and conventional HU values were extracted and normalized to the thoracic aorta. Differences between groups were assessed by pairwise Welch's t test. Correlation and linear regression analyses were used to examine the relationship of imaging parameters in LC and PM. Diagnostic accuracy was measured by the area under receiver operator characteristic curve (AUC) and validated based on resampling methods. RESULTS: Significant differences between subgroups of LC and PMs were noted for all imaging parameters, with the highest number of significant pairs for IC. In univariate analysis, only IC was a significant diagnostic feature for discriminating LC from PM (p = 0.03). All quantitative imaging parameters correlated significantly (p < 0.0001, respectively), with the highest correlation between IC and Zeff (r = 0.91), followed by IC and HU (r = 0.76) and Zeff and HU (r = 0.73). Diagnostic models combining IC or Zeff with HU (IC+HU: AUC = 0.73; Zeff+HU: AUC = 0.69; IC+Zeff+HU: AUC = 0.73) were not significantly different and outperformed individual parameters (IC: AUC = 0.57; Zeff: AUC = 0.57; HU: AUC = 0.55) in diagnostic accuracy (p < 0.05, respectively). CONCLUSION: DE-CT-derived IC or Zeff and conventional HU represent complementary imaging parameters, which, if used in combination, may improve the differentiation between LC and PM. KEY POINTS: • Individual quantitative imaging parameters derived from DE-CT (iodine concentration, effective Z) and conventional CT (HU) provide complementary diagnostic information for the differentiation of primary lung cancer and pulmonary metastases. • A combination of conventional HU and DE-CT parameters enhances the diagnostic utility of individual parameters.

Early detection of radiation-induced lung damage with X-ray dark-field radiography in mice.

OBJECTIVE: Assessing the advantage of x-ray dark-field contrast over x-ray transmission contrast in radiography for the detection of developing radiation-induced lung damage in mice. METHODS: Two groups of female C57BL/6 mice (irradiated and control) were imaged obtaining both contrasts monthly for 28 weeks post irradiation. Six mice received 20 Gy of irradiation to the entire right lung sparing the left lung. The control group of six mice was not irradiated. A total of 88 radiographs of both contrasts were evaluated for both groups based on average values for two regions of interest, covering (irradiated) right lung and healthy left lung. The ratio of these average values, R, was distinguished between healthy and damaged lungs for both contrasts. The time-point when deviations of R from healthy lung exceeded 3σ was determined and compared among contrasts. The Wilcoxon-Mann-Whitney test was used to test against the null hypothesis that there is no difference between both groups. A selection of 32 radiographs was assessed by radiologists. Sensitivity and specificity were determined in order to compare the diagnostic potential of both contrasts. Inter-reader and intra-reader accuracy were rated with Cohen's kappa. RESULTS: Radiation-induced morphological changes of lung tissue caused deviations from the control group that were measured on average 10 weeks earlier with x-ray dark-field contrast than with x-ray transmission contrast. Sensitivity, specificity, and accuracy doubled using dark-field radiography. CONCLUSION: X-ray dark-field radiography detects morphological changes of lung tissue associated with radiation-induced damage earlier than transmission radiography in a pre-clinical mouse model. KEY POINTS: • Significant deviations from healthy lung due to irradiation were measured after 16 weeks with x-ray dark-field radiography (p = 0.004). • Significant deviations occur on average 10 weeks earlier for x-ray dark-field radiography in comparison to x-ray transmission radiography. • Sensitivity and specificity doubled when using x-ray dark-field radiography instead of x-ray transmission radiography.

Dual-energy CT parameters in correlation to MRI-based apparent diffusion coefficient: evaluation in rectal cancer after radiochemotherapy.

BACKGROUND: Rectal cancer (RC) is a frequent malignancy for which magnetic resonance imaging (MRI) is the most common and accurate imaging. Iodine concentration (IC) can be quantified with spectral dual-layer computed tomography CT (DL-CT), which could improve imaging of RC, especially for evaluation of response to radiochemotherapy (RCT). PURPOSE: To compare a DL-CT system to MRI as the non-invasive imaging gold standard for imaging of RC to evaluate the possibility of a response evaluation with DL-CT. MATERIAL AND METHODS: Eleven patients who received DL-CT as well as MRI before and after RCT of RC were retrospectively included into this study. For each examination, a region of interest (ROI) was placed within the tumor. For MRI, the mean apparent diffusion coefficient (ADC) was assessed. For DL-CT, IC, z-effective, and Hounsfield Units (HU) were measured. IC, z-effective, and HU were normalized to the aorta. ADC was correlated to absolute and relative normalized IC, z-effective, and HU with Spearman's ρ. Differences before and after treatment were tested with Wilcoxon signed-rank test. RESULTS: HU, IC, and Z-effective values in DL-CT images decreased significantly after RCT (P<0.01 for each comparison). The mean ADC increased significantly after RCT. Spearman's ρ of the absolute IC difference and the absolute ADC (both before and after RCT) is high and significant (ρ = 0.73; P = 0.01), whereas the ρ-value for z-effective (ρ = 0.56) or HU (ρ = 0.45) to ADC was lower and non-significant. CONCLUSION: Response evaluation of RC after RCT could be possible with DL-CT via the measurement of IC.

Towards subject-level cerebral infarction classification of CT scans using convolutional networks.

Automatic evaluation of 3D volumes is a topic of importance in order to speed up clinical decision making. We describe a method to classify computed tomography scans on volume level for the presence of non-acute cerebral infarction. This is not a trivial task, as the lesions are often similar to other areas in the brain regarding shape and intensity. A three stage architecture is used for classification: 1) A cranial cavity segmentation network is developed, trained and applied. 2) Region proposals are generated 3) Connected regions are classified using a multi-resolution, densely connected 3D convolutional network. Mean area under curve values for subject level classification are 0.95 for the unstratified test set, 0.88 for stratification by patient age and 0.93 for stratification by CT scanner model. We use a partly segmented dataset of 555 scans of which 186 scans are used in the unstratified test set. Furthermore we examine possible dataset bias for scanner model and patient age parameters. We show a successful application of the proposed three-stage model for full volume classification. In contrast to black-box approaches, the convolutional network's decision can be further assessed by examination of intermediate segmentation results.

Diffusion tensor imaging and tractography for preoperative assessment of benign peripheral nerve sheath tumors.

PURPOSE: To evaluate the diagnostic value of fiber tractography and diffusivity analysis generated from 3D diffusion-weighted (DW) sequences for preoperative assessment of benign peripheral nerve sheath tumors. METHOD: MR imaging at 3 T was performed in 22 patients (mean age 41.9 ±â€¯17.1y, 13 women) with histologically confirmed schwannomas (N = 18) and histologically confirmed neurofibromas (N = 11), including a 3D DW turbo spin echo sequence with fat suppression. Diffusion tensor parameters were computed and fiber tracks were determined. Evaluation was performed by two radiologists and one orthopedic surgeon blinded for final diagnosis. Mean diffusivity was computed to allow further assessment of tumor microstructure. Preoperative fascicle visualization was graded, fascicles were categorized regarding anatomical location and amount of fascicles surrounding the tumor. The agreement of imaging findings with intraoperative findings was assessed. RESULTS: On 78.3 % of the DTI images, the fascicle visualization was rated as good or very good. Tractography differences were observed in schwannomas and neurofibromas, showing schwannomas to be significantly more often located eccentrically to the nerve (94.8 %) than neurofibromas (0 %, P < 0.01). Fascicles were significantly more often continuous (87.5 %) in schwannomas, while in neurofibromas, none of the tracks was graded to be continuous (0 %, P = 0.014). A substantial agreement between fiber tracking and surgical anatomy was found regarding the fascicle courses surrounding the tumor (κ = 0.78). Mean diffusivity of schwannomas (1.5 ±â€¯0.2 × 10-3 mm2/s) was significantly lower than in neurofibromas (1.8 ±â€¯0.2 × 10-3 mm2/s; P < 0.001). The Youden index showed an optimal cutoff at 1.7 × 10-3 mm2/s (sensitivity, 0.91; specificity, 0.78; J = 0.69). CONCLUSIONS: Preoperative diffusion tensor imaging allowed to accurately differentiate between schwannomas and neurofibromas and to describe their location in relation to the nerve fascicles for preoperative planning.

Investigation of the Relationship between MR-Based Supraclavicular Fat Fraction and Thyroid Hormones.

PURPOSE: Brown adipose tissue (BAT) plays a potential role in energy and glucose metabolism in humans. Thyroid hormones (TH) are main regulators of BAT development and function. However, it remains unknown how the magnetic resonance (MR)-based proton density fat fraction (PDFF) of supraclavicular adipose tissue used as a surrogate marker for BAT presence relates to TH. Therefore, the purpose of this analysis was to investigate the relationship between supraclavicular PDFF and serum levels of TH. METHODS: In total, 96 adult volunteers from a large cross-sectional study who underwent additional MR examination of the neck and pelvis were included in this analysis. Segmented PDFF maps of the supraclavicular and gluteal subcutaneous adipose tissue were generated. Delta PDFF was calculated as the difference between gluteal and supraclavicular PDFF and grouped as high (≥12%) or low (<12%) based on the median and the clinical rationale of a high versus low probability of BAT being present. Thyroid-stimulating hormone (mIU/L), free triiodothyronine (FT3, pg/mL) and free thyroxine (FT4, ng/dL) levels were determined in blood samples. Body mass index (BMI) was calculated as weight (kg)/height (m)2. Statistical analyses included the use of paired samples ttest, simple linear regression analysis and a multivariable linear regression analysis. RESULTS: The median age of the subjects (77% female) was 33 years, BMI ranged from 17.2 to 43.1 kg/m2. Supraclavicular and gluteal PDFF differed significantly (76.5 ± 4.8 vs. 89.4 ± 3.5 %, p < 0.01). Supraclavicular PDFF was associated with FT3 in subjects with high delta PDFF (R2 = 0.17, p < 0.01), with higher FT3 being associated with lower supraclavicular PDFF (y = 85.2 + -3.6 x). In a multivariable linear regression analysis considering further potential prognostic factors, the interaction between the delta PDFF group and FT3 remained a predictor for supraclavicular PDFF (B = -4.65, p < 0.01). DISCUSSION/CONCLUSIONS: Supraclavicular PDFF corresponds to the presence of BAT. In the present analysis, supraclavicular PDFF is correlated with FT3 in subjects with high delta PDFF. Therefore, the present findings suggest that biologically active T3 may be involved in the development of supraclavicular BAT.

Age- and BMI-related variations of fat distribution in sacral and lumbar bone marrow and their association with local muscle fat content.

This analysis investigated the age- and BMI-related variations of fat distribution in sacral and lumbar bone marrow and their association with local muscle fat content in order to detect fat distribution patterns and variations in healthy adults using proton density fat fraction (PDFF) measurements. A six-echo 3D spoiled gradient-echo sequence was used for chemical shift encoding-based water-fat separation at the sacral and lower lumbar region in 103 healthy volunteers. PDFF values of the sacrum, 5th lumbar vertebral body, the gluteal and paraspinal muscles were determined. Correlation with age was significant (p < 0.05) for PDFF of the sacrum (men (m): r = 0.58; women (w): r = 0.54), L5 (m: r = 0.58; w: r = 0.54), the gluteal (m: r = 0.51; w: r = 0.44) and paraspinal (m: r = 0.36; w: r = 0.49) muscles in both genders. BMI correlated significantly with the paraspinal musculature in men (r = 0.46) and women (r = 0.33). Correlation testing revealed significant correlations (p < 0.05) between the two osseous (m: r = 0.63, w: r = 0.75) and the muscle compartments (m: r = 0.63, w: r = 0.33) in both genders. Bone marrow and muscle fat infiltration patterns were not significantly associated with each other at the sacral and lower lumbar spine region. The presented data suggest that the two compartments may have distinct pathophysiological fat infiltration patterns. However, further clinical studies are needed to support the results.

Advanced X-ray Imaging Technology.

Since their discovery by Wilhelm Conrad Röntgen in 1895, X-rays have become the most widely available, typically fastest, and usually most cost-effective medical imaging modality today. From the early radiographic approaches using X-ray films as detectors, the portfolio of medical X-ray imaging devices developed into a large range of dedicated instrumentation for various applications. While X-ray imaging has come a long way, there are some physical properties of X-rays, which have not yet been fully exploited, and which may offer quite some room for further enhancements of current X-ray imaging equipment. Firstly, X-ray imaging today is mainly black and white, despite the fact that X-ray generators actually create a full spectrum of X-ray energies, and that the interactions of X-rays that occur within the human body are not the same for all energies and every material. Exploiting these spectral dependencies allows to not only obtain a black and white CT image, but also to obtain more molecularly specific information, which is relevant particularly in oncological precision radiology. The second aspect of X-rays, and so far in radiology mainly neglected and unused, is the physical fact that X-rays can also be interpreted in the wave picture, and not only as presently been done in the particle picture. If interpreted as waves, X-rays-just like visible light-experience a phase shift in matter, and this-if exploited correctly-can produce a new class of X-ray images, which then depict the wave interactions of X-rays with matter, rather than only the attenuating properties, as done until now.

CTPA with a conventional CT at 100 kVp vs. a spectral-detector CT at 120 kVp: Comparison of radiation exposure, diagnostic performance and image quality.

PURPOSE: To compare CT pulmonary angiographies (CTPAs) as well as phantom scans obtained at 100 kVp with a conventional CT (C-CT) to virtual monochromatic images (VMI) obtained with a spectral detector CT (SD-CT) at equivalent dose levels as well as to compare the radiation exposure of both systems. MATERIAL AND METHODS: In total, 2110 patients with suspected pulmonary embolism (PE) were examined with both systems. For each system (C-CT and SD-CT), imaging data of 30 patients with the same mean CT dose index (4.85 mGy) was used for the reader study. C-CT was performed with 100 kVp and SD-CT was performed with 120 kVp; for SD-CT, virtual monochromatic images (VMI) with 40, 60 and 70 keV were calculated. All datasets were evaluated by three blinded radiologists regarding image quality, diagnostic confidence and diagnostic performance (sensitivity, specificity). Contrast-to-noise ratio (CNR) for different iodine concentrations was evaluated in a phantom study. RESULTS: CNR was significantly higher with VMI at 40 keV compared to all other datasets. Subjective image quality as well as sensitivity and specificity showed the highest values with VMI at 60 keV and 70 keV. Hereby, a significant difference to 100 kVp (C-CT) was found for image quality. The highest sensitivity was found using VMI at 60 keV with a sensitivity of more than 97 % for all localizations of PE. For diagnostic confidence and subjective contrast, highest values were found with VMI at 40 keV. CONCLUSION: Higher levels of diagnostic performance and image quality were achieved for CPTAs with SD-CT compared to C-CT given similar dose levels. In the clinical setting SD-CT may be the modality of choice as additional spectral information can be obtained.

Gold Nanoparticle Mediated Multi-Modal CT Imaging of Hsp70 Membrane-Positive Tumors.

Imaging techniques such as computed tomographies (CT) play a major role in clinical imaging and diagnosis of malignant lesions. In recent years, metal nanoparticle platforms enabled effective payload delivery for several imaging techniques. Due to the possibility of surface modification, metal nanoparticles are predestined to facilitate molecular tumor targeting. In this work, we demonstrate the feasibility of anti-plasma membrane Heat shock protein 70 (Hsp70) antibody functionalized gold nanoparticles (cmHsp70.1-AuNPs) for tumor-specific multimodal imaging. Membrane-associated Hsp70 is exclusively presented on the plasma membrane of malignant cells of multiple tumor entities but not on corresponding normal cells, predestining this target for a tumor-selective in vivo imaging. In vitro microscopic analysis revealed the presence of cmHsp70.1-AuNPs in the cytosol of tumor cell lines after internalization via the endo-lysosomal pathway. In preclinical models, the biodistribution as well as the intratumoral enrichment of AuNPs were examined 24 h after i.v. injection in tumor-bearing mice. In parallel to spectral CT analysis, histological analysis confirmed the presence of AuNPs within tumor cells. In contrast to control AuNPs, a significant enrichment of cmHsp70.1-AuNPs has been detected selectively inside tumor cells in different tumor mouse models. Furthermore, a machine-learning approach was developed to analyze AuNP accumulations in tumor tissues and organs. In summary, utilizing mHsp70 on tumor cells as a target for the guidance of cmHsp70.1-AuNPs facilitates an enrichment and uniform distribution of nanoparticles in mHsp70-expressing tumor cells that enables various microscopic imaging techniques and spectral-CT-based tumor delineation in vivo.