Human prion diseases and the prion protein - what is the current state of knowledge?

Prion diseases and the prion protein are only partially understood so far in many aspects. This explains the continued research on this topic, calling for an overview on the current state of knowledge. The main objective of the present review article is to provide a comprehensive up-to-date presentation of all major features of human prion diseases bridging the gap between basic research and clinical aspects. Starting with the prion protein, current insights concerning its physiological functions and the process of pathological conversion will be highlighted. Diagnostic, molecular, and clinical aspects of all human prion diseases will be discussed, including information concerning rare diseases like prion-associated amyloidoses and Huntington disease-like 1, as well as the question about a potential human threat due to the transmission of prions from prion diseases of other species such as chronic wasting disease. Finally, recent attempts to develop future therapeutic strategies will be addressed.

Cervical myelitis: a practical approach to its differential diagnosis on MR imaging.

BACKGROUND: Differential diagnosis of non-compressive cervical myelopathy encompasses a broad spectrum of inflammatory, infectious, vascular, neoplastic, neurodegenerative, and metabolic etiologies. Although the speed of symptom onset and clinical course seem to be specific for certain neurological diseases, lesion pattern on MR imaging is a key player to confirm diagnostic considerations. METHODS: The differentiation between acute complete transverse myelitis and acute partial transverse myelitis makes it possible to distinguish between certain entities, with the latter often being the onset of multiple sclerosis. Typical medullary MRI lesion patterns include a) longitudinal extensive transverse myelitis, b) short-range ovoid and peripheral lesions, c) polio-like appearance with involvement of the anterior horns, and d) granulomatous nodular enhancement prototypes. RESULTS AND CONCLUSION: Cerebrospinal fluid analysis, blood culture tests, and autoimmune antibody testing are crucial for the correct interpretation of imaging findings. The combination of neuroradiological features and neurological and laboratory findings including cerebrospinal fluid analysis improves diagnostic accuracy. KEY POINTS: · The differentiation of medullary lesion patterns, i. e., longitudinal extensive transverse, short ovoid and peripheral, polio-like, and granulomatous nodular, facilitates the diagnosis of myelitis.. · Discrimination of acute complete and acute partial transverse myelitis makes it possible to categorize different entities, with the latter frequently being the overture of multiple sclerosis (MS).. · Neuromyelitis optica spectrum disorders (NMOSD) may start as short transverse myelitis and should not be mistaken for MS.. · The combination of imaging features and neurological and laboratory findings including cerebrospinal fluid analysis improves diagnostic accuracy.. · Additional brain imaging is mandatory in suspected demyelinating, systemic autoimmune, infectious, paraneoplastic, and metabolic diseases..

Mechanical thrombectomy for acute ischemic stroke in COVID-19 patients: multicenter experience in 111 cases.

BACKGROUND: Data on the frequency and outcome of mechanical thrombectomy (MT) for large vessel occlusion (LVO) in patients with COVID-19 is limited. Addressing this subject, we report our multicenter experience. METHODS: A retrospective cohort study was performed of consecutive acute stroke patients with COVID-19 infection treated with MT at 26 tertiary care centers between January 2020 and November 2021. Baseline demographics, angiographic outcome and clinical outcome evaluated by the modified Rankin Scale (mRS) at discharge and 90 days were noted. RESULTS: We identified 111 out of 11 365 (1%) patients with acute or subsided COVID-19 infection who underwent MT due to LVO. Cardioembolic events were the most common etiology for LVO (38.7%). Median baseline National Institutes of Health Stroke Scale score and Alberta Stroke Program Early CT Score were 16 (IQR 11.5-20) and 9 (IQR 7-10), respectively. Successful reperfusion (mTICI ≥2b) was achieved in 97/111 (87.4%) patients and 46/111 (41.4%) patients were reperfused completely. The procedure-related complication rate was 12.6% (14/111). Functional independence was achieved in 20/108 (18.5%) patients at discharge and 14/66 (21.2%) at 90 days follow-up. The in-hospital mortality rate was 30.6% (33/108). In the subgroup analysis, patients with severe acute COVID-19 infection requiring intubation had a mortality rate twice as high as patients with mild or moderate acute COVID-19 infection. Acute respiratory failure requiring ventilation and time interval from symptom onset to groin puncture were independent predictors for an unfavorable outcome in a logistic regression analysis. CONCLUSION: Our study showed a poor clinical outcome and high mortality, especially in patients with severe acute COVID-19 infection undergoing MT due to LVO.

Head and neck single- and dual-energy CT: differences in radiation dose and image quality of 2nd and 3rd generation dual-source CT.

OBJECTIVES: To compare radiation dose and image quality of single-energy (SECT) and dual-energy (DECT) head and neck CT examinations performed with second- and third-generation dual-source CT (DSCT) in matched patient cohorts. METHODS: 200 patients (mean age 55.1 ± 16.9 years) who underwent venous phase head and neck CT with a vendor-preset protocol were retrospectively divided into four equal groups (n = 50) matched by gender and BMI: second (Group A, SECT, 100-kV; Group B, DECT, 80/Sn140-kV), and third-generation DSCT (Group C, SECT, 100-kV; Group D, DECT, 90/Sn150-kV). Assessment of radiation dose was performed for an average scan length of 27 cm. Contrast-to-noise ratio measurements and dose-independent figure-of-merit calculations of the submandibular gland, thyroid, internal jugular vein, and common carotid artery were analyzed quantitatively. Qualitative image parameters were evaluated regarding overall image quality, artifacts and reader confidence using 5-point Likert scales. RESULTS: Effective radiation dose (ED) was not significantly different between SECT and DECT acquisition for each scanner generation (p = 0.10). Significantly lower effective radiation dose (p < 0.01) values were observed for third-generation DSCT groups C (1.1 ± 0.2 mSv) and D (1.0 ± 0.3 mSv) compared to second-generation DSCT groups A (1.8 ± 0.1 mSv) and B (1.6 ± 0.2 mSv). Figure-of-merit/contrast-to-noise ratio analysis revealed superior results for third-generation DECT Group D compared to all other groups. Qualitative image parameters showed non-significant differences between all groups (p > 0.06). CONCLUSION: Contrast-enhanced head and neck DECT can be performed with second- and third-generation DSCT systems without radiation penalty or impaired image quality compared with SECT, while third-generation DSCT is the most dose efficient acquisition method. ADVANCES IN KNOWLEDGE: Differences in radiation dose between SECT and DECT of the dose-vulnerable head and neck region using DSCT systems have not been evaluated so far. Therefore, this study directly compares radiation dose and image quality of standard SECT and DECT protocols of second- and third-generation DSCT platforms.

Can Dual-energy CT-based Virtual Monoenergetic Imaging Improve the Assessment of Hypodense Liver Metastases in Patients With Hepatic Steatosis?

RATIONALE AND OBJECTIVES: To evaluate the impact of noise-optimized virtual monoenergetic imaging (VMI) on lesion demarcation and measuring accuracy of hypoattenuating liver metastases in patients with fatty liver disease compared to standard reconstructions. MATERIALS AND METHODS: Twenty-eight patients (mean age 62.2 ± 7.7 years) with fatty liver disease and hypoattenuating liver metastases who underwent unenhanced and contrast-enhanced portal-venous dual-energy CT (DECT) were enrolled. Standard linearly blended and VMI series were reconstructed in 10-keV intervals. Lesion-to-parenchyma contrast-to-noise ratio (CNR) was calculated and the best VMI series was further investigated in a subjective evaluation of overall image quality and lesion demarcation. Size measurements were performed independently by measuring all hypodense lesions (n = 58) twice in a predefined sequence. Inter- and intra-rater agreement was assessed using intra-class correlation coefficient (ICC) statistics. RESULTS: The calculated CNR was greatest at 40-keV VMI (4.3 ± 2.6), significantly higher compared to standard reconstructions (2.9 ± 1.9; p < 0.001). Subjective ratings for overall image quality showed no significant difference between the 2 reconstruction techniques (both medians 4; p = 0.147), while lesion margin demarcation was found to be superior for 40-keV VMI (median 5; p ≤ 0.001). Inter- (ICC, 0.98 for 40-keV VMI; ICC, 0.93 for standard reconstruction) and intra-rater (ICC, 0.99 for 40-keV VMI; ICC, 0.94 for standard image series) analysis showed an excellent agreement for lesion measurements in both reconstruction techniques. CONCLUSION: Noise-optimized VMI reconstructions significantly improve contrast and lesion demarcation of hypoattenuating liver metastases in patients with the fatty liver disease compared to standard reconstruction.

Radiomics of high-resolution computed tomography for the differentiation between cholesteatoma and middle ear inflammation: effects of post-reconstruction methods in a dual-center study.

OBJECTIVES: To evaluate the performance of radiomic features extracted from high-resolution computed tomography (HRCT) for the differentiation between cholesteatoma and middle ear inflammation (MEI), and to investigate the impact of post-reconstruction harmonization and data resampling. METHODS: One hundred patients were included in this retrospective dual-center study: 48 with histology-proven cholesteatoma (center A: 23; center B: 25) and 52 with MEI (A: 27; B: 25). Radiomic features (co-occurrence and run-length matrix, absolute gradient, autoregressive model, Haar wavelet transform) were extracted from manually defined 2D-ROIs. The ten best features for lesion differentiation were selected using probability of error and average correlation coefficients. A multi-layer perceptron feed-forward artificial neural network (MLP-ANN) was used for radiomics-based classification, with histopathology serving as the reference standard (70% of cases for training, 30% for validation). The analysis was performed five times each on (a) unmodified data and on data that were (b) resampled to the same matrix size, and (c) corrected for acquisition protocol differences using ComBat harmonization. RESULTS: Using unmodified data, the MLP-ANN classification yielded an overall median area under the receiver operating characteristic curve (AUC) of 0.78 (0.72-0.84). Using original data from center A and resampled data from center B, an overall median AUC of 0.88 (0.82-0.99) was yielded, while using ComBat harmonized data, an overall median AUC of 0.89 (0.79-0.92) was revealed. CONCLUSION: Radiomic features extracted from HRCT differentiate between cholesteatoma and MEI. When using multi-centric data obtained with differences in CT acquisition parameters, data resampling and ComBat post-reconstruction harmonization clearly improve radiomics-based lesion classification. KEY POINTS: • Unenhanced high-resolution CT coupled with radiomics analysis may be useful for the differentiation between cholesteatoma and middle ear inflammation. • Pooling of data extracted from inhomogeneous CT datasets does not appear meaningful without further post-processing. • When using multi-centric CT data obtained with differences in acquisition parameters, post-reconstruction harmonization and data resampling clearly improve radiomics-based soft-tissue differentiation.

Prevalence and prognostic impact of nonischemic late gadolinium enhancement in stress cardiac magnetic resonance.

AIM: To assess the prevalence and prognostic significance of NI-LGE in patients undergoing stress-CMR. METHODS: Stress-CMR with either dipyridamole or adenosine was performed in 283 patients (228 men, 81%) including perfusion imaging, wall motion evaluation and LGE. Follow-up was completed in all enrolled patients (median time: 1850 days; interquartile range: 1225-2705 days). Composite endpoint included cardiac death, ventricular tachycardia, myocardial infarction, stroke, hospitalization for cardiac cause and coronary revascularization performed beyond 90 days from stress-CMR scans. RESULTS: One hundred and twelve patients (40%) had negative LGE (no-LGE), 140 patients (49%) I-LGE and 31 patients (11%) NI-LGE. Twenty-five events occurred in the no-LGE group, 68 in I-LGE and 11 in the NI-LGE group. On survival curves, patients with NI-LGE had worse prognosis than patients with no-LGE regardless of the presence of inducible perfusion defects. No significant prognostic differences were found between I-LGE and NI-LGE. CONCLUSION: NI-LGE can be detected in 11% of patients during stress-CMR providing a diagnosis of nonischemic cardiac disease. Patients with NI-LGE have worse prognosis than those with no-LGE.

Outcomes of Cardiovascular Magnetic Resonance Imaging in Patients Recently Recovered From Coronavirus Disease 2019 (COVID-19).

IMPORTANCE: Coronavirus disease 2019 (COVID-19) continues to cause considerable morbidity and mortality worldwide. Case reports of hospitalized patients suggest that COVID-19 prominently affects the cardiovascular system, but the overall impact remains unknown. OBJECTIVE: To evaluate the presence of myocardial injury in unselected patients recently recovered from COVID-19 illness. DESIGN, SETTING, AND PARTICIPANTS: In this prospective observational cohort study, 100 patients recently recovered from COVID-19 illness were identified from the University Hospital Frankfurt COVID-19 Registry between April and June 2020. EXPOSURE: Recent recovery from severe acute respiratory syndrome coronavirus 2 infection, as determined by reverse transcription-polymerase chain reaction on swab test of the upper respiratory tract. MAIN OUTCOMES AND MEASURES: Demographic characteristics, cardiac blood markers, and cardiovascular magnetic resonance (CMR) imaging were obtained. Comparisons were made with age-matched and sex-matched control groups of healthy volunteers (n = 50) and risk factor-matched patients (n = 57). RESULTS: Of the 100 included patients, 53 (53%) were male, and the mean (SD) age was 49 (14) years. The median (IQR) time interval between COVID-19 diagnosis and CMR was 71 (64-92) days. Of the 100 patients recently recovered from COVID-19, 67 (67%) recovered at home, while 33 (33%) required hospitalization. At the time of CMR, high-sensitivity troponin T (hsTnT) was detectable (greater than 3 pg/mL) in 71 patients recently recovered from COVID-19 (71%) and significantly elevated (greater than 13.9 pg/mL) in 5 patients (5%). Compared with healthy controls and risk factor-matched controls, patients recently recovered from COVID-19 had lower left ventricular ejection fraction, higher left ventricle volumes, and raised native T1 and T2. A total of 78 patients recently recovered from COVID-19 (78%) had abnormal CMR findings, including raised myocardial native T1 (n = 73), raised myocardial native T2 (n = 60), myocardial late gadolinium enhancement (n = 32), or pericardial enhancement (n = 22). There was a small but significant difference between patients who recovered at home vs in the hospital for native T1 mapping (median [IQR], 1119 [1092-1150] ms vs 1141 [1121-1175] ms; P = .008) and hsTnT (4.2 [3.0-5.9] pg/dL vs 6.3 [3.4-7.9] pg/dL; P = .002) but not for native T2 mapping. None of these measures were correlated with time from COVID-19 diagnosis (native T1: r = 0.07; P = .47; native T2: r = 0.14; P = .15; hsTnT: r = -0.07; P = .50). High-sensitivity troponin T was significantly correlated with native T1 mapping (r = 0.33; P < .001) and native T2 mapping (r = 0.18; P = .01). Endomyocardial biopsy in patients with severe findings revealed active lymphocytic inflammation. Native T1 and T2 were the measures with the best discriminatory ability to detect COVID-19-related myocardial pathology. CONCLUSIONS AND RELEVANCE: In this study of a cohort of German patients recently recovered from COVID-19 infection, CMR revealed cardiac involvement in 78 patients (78%) and ongoing myocardial inflammation in 60 patients (60%), independent of preexisting conditions, severity and overall course of the acute illness, and time from the original diagnosis. These findings indicate the need for ongoing investigation of the long-term cardiovascular consequences of COVID-19.

Measurement Reliability and Diagnostic Accuracy of Virtual Monoenergetic Dual-Energy CT in Patients with Colorectal Liver Metastases.

RATIONALE AND OBJECTIVES: To compare dual-energy CT virtual monoenergetic images (VMI) and standard reconstructions for reliability of quantitative size measurements and diagnostic accuracy for the detection of colorectal liver metastases (CRLM). MATERIALS AND METHODS: We retrospectively included 98 patients (mean age, 61.1±11.5 years) with colorectal cancer, of whom 49 subjects had CRLM. All patients underwent a portal-venous phase dual-energy CT examination. Standard linearly-blended reformats and 40-keV VMI were reconstructed. For both reconstruction techniques, two blinded readers performed measurements of CRLM twice in a preset sequence. Three additional radiologists independently assessed all liver lesions in terms of dignity (benign vs. malignant). Sensitivity, specificity and diagnostic accuracy were calculated on a per-patient basis using MRI as reference standard. Readers scored the suitability for metric measurements and their diagnostic confidence using 5-point Likert scales. Inter-rater agreement was evaluated using intraclass correlation coefficient (ICC). RESULTS: Inter-rater agreement for lesion size measurements was higher for 40-keV VMI (ICC, 0.88) compared to standard linearly-blended series (ICC, 0.80). Sensitivity and diagnostic accuracy for the detection of CRLM were significantly higher for VMI at 40-keV compared to standard reconstructions (90.6% vs. 80.6%, and 89.1% vs. 81.3%; p < 0.001). Reader scores indicated that 40-keV VMI were more suitable for metric lesion measurements and provided greater diagnostic confidence compared to standard reformats (median, 5 vs. 3, and 5 vs. 4; both p < 0.001). CONCLUSION: Low-keV VMI reconstructions improve reliability of quantitative size measurements and diagnostic accuracy for the assessment of CRLM compared to standard linearly-blended images.

CMR imaging biosignature of cardiac involvement due to cancer-related treatment by T1 and T2 mapping.

BACKGROUND: Cancer-related treatment is associated with development of heart failure and poor outcome in cancer-survivors. T1 and T2 mapping by cardiovascular magnetic resonance (CMR) may detect myocardial injury due to cancer-related treatment. METHODS: Patients receiving cancer-related treatment regimes underwent screening of cardiac involvement with CMR, either within 3 months (early Tx) or >12 months (late Tx) post-treatment. T1 and T2 mapping, cardiac function, strain, ischaemia-testing, scar-imaging and serological cardiac biomarkers were obtained. RESULTS: Compared to age/gender matched controls (n = 57), patients (n = 115, age (yrs): median(IQR) 48(28-60), females, n = 60(52%) had reduced left ventricular ejection fraction (LV-EF) and strain, and higher native T1 and T2. The early Tx group (n = 52) had significantly higher native T1, T2 and troponin levels compared to the late Tx group, indicating myocardial inflammation and oedema (p < 0.01). On the contrary, late Tx patients showed raised native T1, increased LV-end-systolic volumes, reduced LV-EF and deformation, and elevated NT-proBNP, suggesting myocardial fibrosis and remodelling (p < 0.05). Prospective validation of these results in an independent cohort of patients with similar treatment regimens (n = 25) and longitudinal assessments revealed high concordance of CMR imaging signatures of early and late cardiac involvement. CONCLUSIONS: Native T1 and T2 mapping can be valuable in detecting and monitoring of cardiac involvement with cancer-related treatment, providing distinct biosignatures of early inflammatory involvement (raised native T1 and T2) and interstitial fibrosis and remodelling (raised native T1 but not T2), respectively. Our findings may provide an algorithm allowing to identify susceptible myocardium to potentially guide cardio-protective treatment measures.

Improved long-term durability of allogeneic heart valves in the orthotopic sheep model.

OBJECTIVES: Frozen cryopreservation (FC) with the vapour phase of liquid nitrogen storage (-135°C) is a standard biobank technique to preserve allogeneic heart valves to enable a preferable allograft valve replacement in clinical settings. However, their long-term function is limited by immune responses, inflammation and structural degeneration. Ice-free cryopreserved (IFC) valves with warmer storage possibilities at -80°C showed better matrix preservation and decreased immunological response in preliminary short-term in vivo studies. Our study aimed to assess the prolonged performance of IFC allografts in an orthotopic pulmonary sheep model. METHODS: FC (n = 6) and IFC (n = 6) allografts were transplanted into juvenile Merino sheep. After 12 months of implantation, functionality testing via 2-dimensional echocardiography and histological analyses was performed. In addition, multiphoton autofluorescence imaging and Raman microspectroscopy analysis were applied to qualitatively and quantitatively assess the matrix integrity of the leaflets. RESULTS: Six animals from the FC group and 5 animals from the IFC group were included in the analysis. Histological explant analysis showed early inflammation in the FC valves, whereas sustainable, fully functional, devitalized acellular IFC grafts were obtained. IFC valves showed excellent haemodynamic data with fewer gradients, no pulmonary regurgitation, no calcification and acellularity. Structural remodelling of the leaflet matrix structure was only detected in FC-treated tissue, whereas IFC valves maintained matrix integrity comparable to that of native controls. The collagen crimp period and amplitude and elastin structure were significantly different in the FC valve cusps compared to IFC and native cusps. Collagen fibres in the FC valves were less aligned and straightened. CONCLUSIONS: IFC heart valves with good haemodynamic function, reduced immunogenicity and preserved matrix structures have the potential to overcome the known limitations of the clinically applied FC valve.

Gadolinium-enhanced imaging of pediatric thoracic lymphoma: is intravenous contrast really necessary?

OBJECTIVES: Increasing awareness of potential side effects from gadolinium-based contrast agents has underlined the need for contrast-free magnetic resonance imaging (MRI). Numerous recent articles evaluated the risk of potential brain deposits, with the result that research is putting the focus more on alternative unenhanced imaging techniques. The aim of this study was to determine the need for contrast media for chest MRI in primary staging and follow-up care of lymphoma. METHODS: This monocentric, retrospective study encompassed patients under 25 years of age who had undergone histopathological examination of thoracic lymph nodes and at least one chest MRI examination with unenhanced and contrast-enhanced sequences. Seven different thoracic lymph node stations including mediastinal, hilar, periclavicular, and axillary regions were evaluated by two readers regarding lesion diameter, number, shape, necrosis, and infiltration of surrounding structures. Findings were categorized into suspicious (> 1 cm; round; necrosis; infiltration) or non-suspicious. RESULTS: Fifty-one patients (mean age, 16.0 ± 3.7 yrs) with thoracic Hodgkin (70.6%) and non-Hodgkin lymphoma (25.5%) and lymphadenopathy (3.9%) were retrospectively included. Most lymph nodes categorized as suspicious were located in the mediastinal station (86.4%). High agreement (κ = 0.81) between unenhanced and contrast-enhanced sequences was found for both suspicious and non-suspicious lymph nodes. Significant (p < 0.001), but small difference (1 mm) was observed only in sizing mediastinal lymph nodes (all other p > 0.05). No significant difference (smallest p = 0.08) was shown for the use of five different types of contrast media. CONCLUSION: MRI in young patients with thoracic lymphoma can safely be done without the use of contrast agent. KEY POINT: • Thoracic magnetic resonance imaging in young lymphoma patients can safely be done without gadolinium-based contrast agents.

High-sensitive troponin is associated with subclinical imaging biosignature of inflammatory cardiovascular involvement in systemic lupus erythematosus.

BACKGROUND: Cardiovascular (CV) involvement in patients with systemic lupus erythematosus (SLE) is presumably subclinical for the major part of its evolution. We evaluated the associations between high-sensitive troponin T (hs-TropT), a sensitive marker of myocardial injury, and CV involvement using cardiac magnetic resonance (CMR). METHODS AND RESULTS: This is a two-centre (London and Frankfurt) CMR imaging study at 3.0 Tesla of consecutive 92 patients with SLE free of cardiac symptoms, undergoing screening for cardiac involvement. Venous samples were drawn and analysed post-hoc for cardiac biomarkers, including hs-TropT, high-sensitive C reactive protein and N-terminal pro brain natriuretic peptide. Compared with age-matched/gender-matched non-SLE controls (n=78), patients had significantly raised cardiac biomarker levels, native T1 and T2, aortic and ventricular stiffness, and reduced global longitudinal strain (p<0.01). In SLE, hs-TropT was significantly and independently associated with native T2, followed by the models including native T1 and aortic stiffness (Χ2 0.462, p<0.01). There were no relationships between hs-TropT and age, gender, CV risk factors, duration of systemic disease, cardiac structure or function, or late gadolinium enhancement. CONCLUSIONS: Patients with SLE have a high prevalence of subclinical myocardial injury as demonstrated by raised high-sensitive troponin levels. CMR with T2 mapping reveals myocardial oedema as the strongest predictor of hs-TropT release, underscoring the inflammatory interstitial remodelling as the main mechanism of injury. Patients without active myocardial inflammation demonstrate diffuse interstitial remodelling and increased vascular stiffness. These findings substantiate the role of CMR in screening of subclinical cardiac involvement. TRIAL REGISTRATION NUMER: NCT02407197; Results.

Dual-energy CT in patients with colorectal cancer: Improved assessment of hypoattenuating liver metastases using noise-optimized virtual monoenergetic imaging.

PURPOSE: To assess the value of the noise-optimized virtual monoenergetic imaging (VMI+) technique on quantitative and qualitative image parameters in patients with hypoattenuating liver metastases from colorectal cancer (CRC) at abdominal dual-energy CT (DECT). MATERIALS AND METHODS: Fifty-three consecutive patients (mean age, 70.3 ± 11.4 years; range, 44-86 years) with histologically proven, hypoattenuating liver metastases from CRC were retrospectively included in this IRB-approved study. DECT datasets were reconstructed as standard linearly-blended M_0.6 image series, traditional virtual monoenergetic images (VMI), and noise-optimized VMI+ series. VMI and VMI+ reconstructions were obtained at energy levels ranging from 40 to 100-keV with 10-keV increments. Signal attenuation of liver parenchyma and liver metastases was measured to calculate signal-to-noise (SNR) and contrast-to-noise (CNR) ratios. Each image series was subjectively rated by three blinded radiologists with regard to image quality, lesion delineation, and image noise using a five-point Likert scale. RESULTS: Quantitative image quality parameters peaked at 40-keV VMI+ (SNR, 8.1 ± 3.4; CNR, 6.5 ± 2.6) with statistically significant differences in comparison with standard reconstructions and all traditional VMI series (P ≤ 0.001). Qualitative image analysis revealed best rating scores for 60-keV VMI+ series (median, 5) with significant differences compared to linearly-blended M_0.6 and all traditional VMI series (P ≤ 0.001). Lesion delineation showed significantly superior ratings for 40-keV VMI+ series compared to all other reconstructions (median, 5) (P ≤ 0.001). CONCLUSION: Low-keV VMI+ reconstructions demonstrate significantly increased quantitative and qualitative image quality parameters in patients with hypoattenuating liver metastases from CRC in comparison with standard reconstructions and traditional VMI series at abdominal DECT. Best lesion delineation can be achieved at 40-keV VMI+.

Dual-energy CT-based iodine quantification to differentiate abdominal malignant lymphoma from lymph node metastasis.

PURPOSE: To investigate the value of dual-energy computed tomography (DECT)-derived iodine and fat quantification in differentiating malignant abdominal lymphoma from lymph node metastasis. MATERIALS AND METHODS: In this retrospective study, 59 patients (39 men; mean age, 62.7 years) with histopathologically-confirmed diagnosis of either malignant lymphoma or lymph node metastasis were included. For each lesion, contrast-enhanced attenuation, as well as DECT-derived iodine density and fat fraction measurements were recorded. Mean attenuation and material density values were compared between malignant lymphomas and lymph node metastases. The receiver operating characteristic (ROC) curve analysis was adopted to estimate the optimal threshold for discriminating between both entities. A control group (n = 60) was analyzed for comparison of attenuation and material density values of normal abdominal lymph nodes. RESULTS: Assessment of DECT-derived iodine density and fat fraction values revealed significant differences between lymph node metastases (1.7 ±â€¯0.4 mg/ml and 15.5 ±â€¯7.3%) and malignant lymphomas (2.5 ±â€¯0.5 mg/ml and 26.7 ±â€¯12.2%) as well as normal lymph nodes (2.4 ±â€¯0.8 mg/ml and 24.1 ±â€¯10.8%) (P ≤ 0.013). An iodine concentration of 2.0 mg/ml represented the optimal threshold to discriminate between lymphoma and lymph node metastasis (sensitivity, 87%; specificity, 89%). Moreover, a significant correlation was found between iodine concentration and fat fraction for both lymphomas and lymph node metastases (P = 0.001). CONCLUSION: DECT enables characterization of abdominal masses as derived iodine and fat fraction values differ significantly between malignant abdominal lymphomas and lymph node metastases.

Using coronary CT angiography for guiding invasive coronary angiography: potential role to reduce intraprocedural radiation exposure.

OBJECTIVES: We investigated the potential reduction of patient exposure during invasive coronary angiography (ICA) if the procedure had only been directed to the vessel with at least one ≥ 50% stenosis as described in the CT report. METHODS: Dose reports of 61 patients referred to ICA because of at least one ≥ 50% stenosis on coronary CT angiography (CCTA) were included. Dose-area product (DAP) was documented separately for left (LCA) and right coronary arteries (RCA) by summing up the single DAP for each angiographic projection. The study population was subdivided as follows: coronary intervention of LCA (group 1) or RCA (group 2) only, or of both vessels (group 3), or further bypass grafting (group 4), or no further intervention (group 5). RESULTS: 57.4% of the study population could have benefitted from reduced exposure if catheterization had been directly guided to the vessel of interest as described on CCTA. Mean relative DAP reductions were as follows: group 1 (n = 18), 11.2%; group 2 (n = 2), 40.3%; group 3 (n = 10), 0%; group 4 (n = 3), 0%; group 5 (n = 28), 28.8%. CONCLUSIONS: Directing ICA to the vessel with stenosis as described on CCTA would reduce intraprocedural patient exposure substantially, especially for patients with single-vessel stenosis. KEY POINTS: • Patients with CAD can benefit from decreased radiation exposure during coronary angiography. • ICA should be directed solely to significant stenoses as described on CCTA. • Severely calcified plaques remain a limitation of CCTA leading to unnecessary ICA referrals.

Impact of T-cell-mediated immune response on xenogeneic heart valve transplantation: short-term success and mid-term failure.

OBJECTIVES: Allogeneic frozen cryopreserved heart valves (allografts or homografts) are commonly used in clinical practice. A major obstacle for their application is the limited availability in particular for paediatrics. Allogeneic large animal studies revealed that alternative ice-free cryopreservation (IFC) results in better matrix preservation and reduced immunogenicity. The objective of this study was to evaluate xenogeneic (porcine) compared with allogeneic (ovine) IFC heart valves in a large animal study. METHODS: IFC xenografts and allografts were transplanted in 12 juvenile merino sheep for 1-12 weeks. Immunohistochemistry, ex vivo computed tomography scans and transforming growth factor-ß release profiles were analysed to evaluate postimplantation immunopathology. In addition, near-infrared multiphoton imaging and Raman spectroscopy were employed to evaluate matrix integrity of the leaflets. RESULTS: Acellular leaflets were observed in both groups 1 week after implantation. Allogeneic leaflets remained acellular throughout the entire study. In contrast, xenogeneic valves were infiltrated with abundant T-cells and severely thickened over time. No collagen or elastin changes could be detected in either group using multiphoton imaging. Raman spectroscopy with principal component analysis focusing on matrix-specific peaks confirmed no significant differences for explanted allografts. However, xenografts demonstrated clear matrix changes, enabling detection of distinct inflammatory-driven changes but without variations in the level of transforming growth factor-ß. CONCLUSIONS: Despite short-term success, mid-term failure of xenogeneic IFC grafts due to a T-cell-mediated extracellular matrix-triggered immune response was shown.

Monoenergetic Dual-energy Computed Tomographic Imaging: Cardiothoracic Applications.

Monoenergetic imaging is an increasingly used reconstruction technique in postprocessing of dual-energy computed tomography (DECT). The main advantage of this technique is the ability to substantially increase image contrast of structures with uptake of iodinated contrast material. Although monoenergetic imaging was mainly used in oncological DECT applications, recent research has further demonstrated its role in vascular imaging. Using this dedicated postprocessing algorithm, image contrast of vascular structures in the thorax can be increased, a drastic reduction of contrast material is feasible, and even beam-hardening artifacts can be reduced. The aim of this review article is to explain the technical background of this technique, showcase its relevance in cardiothoracic DECT, and provide an outlook on the clinical impact of this technique beyond solely improvements in image quality.