Spleen Volume Reduction Is a Reliable and Independent Biomarker for Long-Term Risk of Leukopenia Development in Peptide Receptor Radionuclide Therapy.

177Lu-DOTATATE therapy is an effective treatment for advanced neuroendocrine tumors, despite its dose-limiting hematotoxicity. Herein, the significance of off-target splenic irradiation is unknown. Our study aims to identify predictive markers of peptide receptor radionuclide therapy-induced leukopenia. Methods: We retrospectively analyzed blood counts and imaging data of 88 patients with histologically confirmed, unresectable metastatic neuroendocrine tumors who received 177Lu-DOTATATE treatment at our institution from February 2009 to July 2021. Inclusion criterium was a tumor uptake equivalent to or greater than that in the liver on baseline receptor imaging. We excluded patients with less than 24 mo of follow-up and those patients who received fewer than 4 treatment cycles, additional therapies, or blood transfusions during follow-up. Results: Our study revealed absolute and relative white blood cell counts and relative spleen volume reduction as independent predictors of radiation-induced leukopenia at 24 mo. However, a 30% decline in spleen volume 12 mo after treatment most accurately predicted patients proceeding to leukopenia at 24 mo (receiver operating characteristic area under the curve of 0.91, sensitivity of 0.93, and specificity of 0.90), outperforming all other parameters by far. Conclusion: Automated splenic volume assessments demonstrated superior predictive capabilities for the development of leukopenia in patients undergoing 177Lu-DOTATATE treatment compared with conventional laboratory parameters. The reduction in spleen size proves to be a valuable, routinely available, and quantitative imaging-based biomarker for predicting radiation-induced leukopenia. This suggests potential clinical applications for risk assessment and management.

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.

Sparse-sampling computed tomography for detection of endoleak after endovascular aortic repair (EVAR).

OBJECTIVES: To evaluate sparse sampling computed tomography (SpSCT) for detection of endoleak after endovascular aortic repair (EVAR) at different dose levels in terms of subjective image criteria and diagnostic accuracy. METHODS: Twenty clinically indicated computed tomography aortic angiography (CTA) scans were used to obtain simulated low-dose scans with 100%, 50%, 25%, 12.5% and 6.25% of the applicated clinical dose, resulting in five dose levels (DL). From full sampling (FS) data sets, every second (2-SpSCT) or fourth (4-SpSCT) projection was used to generate simulated sparse sampling scans. All examinations were evaluated by four blinded radiologists regarding subjective image criteria and diagnostic performance. RESULTS: Sensitivity was higher than 93% in 4-SpSCT at the 25% DL which is the same as with FS at full dose (100% DL). High accuracies and relative high AUC-values were obtained for 2- and 4-SpSCT down to the 12.5% DL, while for FS similar values were shown down to 25% DL only. Subjective image quality was significantly higher for 4-SpSCT compared to FS at each dose level. More than 90% of all cases were rated with a high or medium confidence for FS and 2-SpSCT at the 50% DL and for 4-SpSCT at the 25% DL. At DL 25% and 12.5%, more cases showed a high confidence using 2- and 4-SpSCT compared with FS. CONCLUSIONS: Via SpSCT, a dose reduction down to a 25% dose level (mean effective dose of 1.49 mSv in the current study) for CTA is possible while maintaining high image quality and full diagnostic confidence.

Correlation of image quality parameters with tube voltage in X-ray dark-field chest radiography: a phantom study.

Grating-based X-ray dark-field imaging is a novel imaging modality with enormous technical progress during the last years. It enables the detection of microstructure impairment as in the healthy lung a strong dark-field signal is present due to the high number of air-tissue interfaces. Using the experience from setups for animal imaging, first studies with a human cadaver could be performed recently. Subsequently, the first dark-field scanner for in-vivo chest imaging of humans was developed. In the current study, the optimal tube voltage for dark-field radiography of the thorax in this setup was examined using an anthropomorphic chest phantom. Tube voltages of 50-125 kVp were used while maintaining a constant dose-area-product. The resulting dark-field and attenuation radiographs were evaluated in a reader study as well as objectively in terms of contrast-to-noise ratio and signal strength. We found that the optimum tube voltage for dark-field imaging is 70 kVp as here the most favorable combination of image quality, signal strength, and sharpness is present. At this voltage, a high image quality was perceived in the reader study also for attenuation radiographs, which should be sufficient for routine imaging. The results of this study are fundamental for upcoming patient studies with living humans.

Prediction of Tumor Cellularity in Resectable PDAC from Preoperative Computed Tomography Imaging.

BACKGROUND: PDAC remains a tumor entity with poor prognosis and a 5-year survival rate below 10%. Recent research has revealed invasive biomarkers, such as distinct molecular subtypes, predictive for therapy response and patient survival. Non-invasive prediction of individual patient outcome however remains an unresolved task. METHODS: Discrete cellularity regions of PDAC resection specimen (n = 43) were analyzed by routine histopathological work up. Regional tumor cellularity and CT-derived Hounsfield Units (HU, n = 66) as well as iodine concentrations were regionally matched. One-way ANOVA and pairwise t-tests were performed to assess the relationship between different cellularity level in conventional, virtual monoenergetic 40 keV (monoE 40 keV) and iodine map reconstructions. RESULTS: A statistically significant negative correlation between regional tumor cellularity in histopathology and CT-derived HU from corresponding image regions was identified. Radiological differentiation was best possible in monoE 40 keV CT images. However, HU values differed significantly in conventional reconstructions as well, indicating the possibility of a broad clinical application of this finding. CONCLUSION: In this study we establish a novel method for CT-based prediction of tumor cellularity for in-vivo tumor characterization in PDAC patients.

Coronary calcium scoring assessed on native screening chest CT imaging as predictor for outcome in COVID-19: An analysis of a hospitalized German cohort.

BACKGROUND: Since the outbreak of the COVID-19 pandemic, a number of risk factors for a poor outcome have been identified. Thereby, cardiovascular comorbidity has a major impact on mortality. We investigated whether coronary calcification as a marker for coronary artery disease (CAD) is appropriate for risk prediction in COVID-19. METHODS: Hospitalized patients with COVID-19 (n = 109) were analyzed regarding clinical outcome after native computed tomography (CT) imaging for COVID-19 screening. CAC (coronary calcium score) and clinical outcome (need for intensive care treatment or death) data were calculated following a standardized protocol. We defined three endpoints: critical COVID-19 and transfer to ICU, fatal COVID-19 and death, composite endpoint critical and fatal COVID-19, a composite of ICU treatment and death. We evaluated the association of clinical outcome with the CAC. Patients were dichotomized by the median of CAC. Hazard ratios and odds ratios were calculated for the events death or ICU or a composite of death and ICU. RESULTS: We observed significantly more events for patients with CAC above the group's median of 31 for critical outcome (HR: 1.97[1.09,3.57], p = 0.026), for fatal outcome (HR: 4.95[1.07,22.9], p = 0.041) and the composite endpoint (HR: 2.31[1.28,4.17], p = 0.0056. Also, odds ratio was significantly increased for critical outcome (OR: 3.01 [1.37, 6.61], p = 0.01) and for fatal outcome (OR: 5.3 [1.09, 25.8], p = 0.02). CONCLUSION: The results indicate a significant association between CAC and clinical outcome in COVID-19. Our data therefore suggest that CAC might be useful in risk prediction in patients with COVID-19.

Multimodality imaging approach in the diagnosis of chronic myocarditis with preserved left ventricular ejection fraction (MCpEF): The role of 2D speckle-tracking echocardiography.

BACKGROUND: Up to one third of patients with chronic myocarditis (MC) have preserved left ventricular (LV) ejection fraction (MCpEF). The purpose of this study was to evaluate the role of adding 2D speckle-tracking echocardiography (STE) to cardiac magnetic resonance imaging (cMRI) in the diagnosis of patients with MCpEF. METHODS AND RESULTS: We analyzed 67 patients with suspected MCpEF who underwent endomyocardial biopsy (EMB). Thirty-two patients with confirmed chronic myocardial inflammation by EMB served as study group (MCpEF) and the remaining patients (n=35) served as control group. In all patients, 2D STE and cMRI were performed within 48h before EMB. Patients with MCpEF had significantly lower LV global longitudinal systolic strain (GLS) than controls (GLS: -17.01±2.42% vs. -19.39±3.81%, p<0.001; respectively). In line, an abnormal GLS had adequate diagnostic performance to detect MCpEF (sensitivity, specificity, and accuracy of 82%, 70%, and 76%, respectively), which was superior to cMRI based on the Lake-Louise criteria (sensitivity, specificity, and accuracy 54%, 71%, and 67%, respectively). In addition, adding GLS to the Lake-Louise criteria improved significantly the diagnostic performance of cMRI to detect MCpEF (sensitivity, specificity, and accuracy 96%, 55%, and 75%, respectively). CONCLUSION: The findings of this study suggest that GLS using 2D STE could play an important role in the diagnostic evaluation of patients with suspected chronic myocarditis with preserved LV ejection fraction (MCpEF).

Hyperemic stress myocardial perfusion cardiovascular magnetic resonance in mice at 3 Tesla: initial experience and validation against microspheres.

BACKGROUND: Dynamic first pass contrast-enhanced myocardial perfusion is the standard CMR method for the estimation of myocardial blood flow (MBF) and MBF reserve in man, but it is challenging in rodents because of the high temporal and spatial resolution requirements. Hyperemic first pass myocardial perfusion CMR during vasodilator stress in mice has not been reported. METHODS: Five C57BL/6 J mice were scanned on a clinical 3.0 Tesla Achieva system (Philips Healthcare, Netherlands). Vasodilator stress was induced via a tail vein catheter with an injection of dipyridamole. Dynamic contrast-enhanced perfusion imaging (Gadobutrol 0.1 mmol/kg) was based on a saturation recovery spoiled gradient echo method with 10-fold k-space and time domain undersampling (k-t PCA). One week later the mice underwent repeat anaesthesia and LV injections of fluorescent microspheres at rest and at stress. Microspheres were analysed using confocal microscopy and fluorescence-activated cell sorting. RESULTS: Mean MBF at rest measured by Fermi-function constrained deconvolution was 4.1 ± 0.5 ml/g/min and increased to 9.6 ± 2.5 ml/g/min during dipyridamole stress (P = 0.005). The myocardial perfusion reserve was 2.4 ± 0.54. The mean count ratio of stress to rest microspheres was 2.4 ± 0.51 using confocal microscopy and 2.6 ± 0.46 using fluorescence. There was good agreement between cardiovascular magnetic resonance CMR and microspheres with no significant difference (P = 0.84). CONCLUSION: First-pass myocardial stress perfusion CMR in a mouse model is feasible at 3 Tesla. Rest and stress MBF values were consistent with existing literature and perfusion reserve correlated closely to microsphere analysis. Data were acquired on a 3 Tesla scanner using an approach similar to clinical acquisition protocols, potentially facilitating translation of imaging findings between rodent and human studies.

Local erythropoietin and endothelial progenitor cells improve regional cardiac function in acute myocardial infarction.

BACKGROUND: Expanded endothelial progenitor cells (eEPC) improve global left ventricular function in experimental myocardial infarction (MI). Erythropoietin beta (EPO) applied together with eEPC may improve regional myocardial function even further by anti-apoptotic and cardioprotective effects. Aim of this study was to evaluate intramyocardial application of eEPCs and EPO as compared to eEPCs or EPO alone in experimental MI. METHODS AND RESULTS: In vitro experiments revealed that EPO dosed-dependently decreased eEPC and leukocyte apoptosis. Moreover, in the presence of EPO mRNA expression in eEPC of proangiogenic and proinflammatory mediators measured by TaqMan PCR was enhanced. Experimental MI was induced by ligation and reperfusion of the left anterior descending coronary artery of nude rats (n = 8-9). After myocardial transplantation of eEPC and EPO CD68+ leukocyte count and vessel density were enhanced in the border zone of the infarct area. Moreover, apoptosis of transplanted CD31 + TUNEL + eEPC was decreased as compared to transplantation of eEPCs alone. Regional wall motion of the left ventricle was measured using Magnetic Resonance Imaging. After injection of eEPC in the presence of EPO regional wall motion significantly improved as compared to injection of eEPCs or EPO alone. CONCLUSION: Intramyocardial transplantation of eEPC in the presence of EPO during experimental MI improves regional wall motion. This was associated with an increased local inflammation, vasculogenesis and survival of the transplanted cells. Local application of EPO in addition to cell therapy may prove beneficial in myocardial remodeling.

Serial contrast-enhanced cardiac magnetic resonance imaging demonstrates regression of hyperenhancement within the coronary artery wall in patients after acute myocardial infarction.

OBJECTIVES: Our aim was to determine whether serial contrast-enhanced cardiac magnetic resonance (CE-CMR) is useful for the characterization of tissue signal changes within the coronary vessel wall in patients after acute myocardial infarction (AMI). BACKGROUND: Inflammation plays a key role in the development of AMI. CE-CMR of the vessel wall has been found useful for the characterization of inflammatory tissue signal changes in patients with carotid artery stenosis, giant cell arteritis, or Takayasu's arteritis; however, it has never been serially performed in the coronary artery wall in patients with acute and chronic myocardial infarction using a gadolinium-based contrast medium and compared with systemic markers of inflammation. METHODS: CE-CMR using a T1-weighted 3-dimensional gradient echo inversion recovery sequence of the coronary artery wall and 0.2 mmol/kg of gadolinium-diethylenetriaminepentaacetic acid was performed in 10 patients with AMI 6 days and 3 months after coronary intervention and in 9 subjects without coronary artery disease on invasive coronary angiography. Contrast-to-noise ratio (CNR) within the coronary artery wall was quantified in comparison with blood signal. RESULTS: Patients with AMI demonstrated a significantly increased coronary vessel wall enhancement 6 days after infarction compared with normal subjects (CNR 7.8 +/- 4.4 vs. 5.3 +/- 3.2, p < 0.001). Three months after infarction, CNR decreased to 6.5 +/- 4.7 (p < 0.03). This decrease paralleled declines in C-reactive protein. Angiographically normal segments showed no contrast changes, but CNR significantly decreased in stenotic segments, from 10.9 +/- 3.8 to 6.8 +/- 5.0 (p < 0.002), resulting in a reduction of enhanced segments from 70% to 25% (p < 0.01). CONCLUSIONS: Serial CE-CMR identified changes in spatial extent and intensity of coronary contrast enhancement in patients after AMI. This technique may be useful for the characterization of transient coronary tissue signal changes, which may represent edema or inflammation during the post-infarction phase. In addition, CE-CMR may offer the potential for visualization of inflammatory activity in atherosclerosis associated with acute coronary syndromes.