Myeloma bone disease imaging on a 1st-generation clinical photon-counting detector CT vs. 2nd-generation dual-source dual-energy CT.

OBJECTIVE: Subjective and objective image quality comparison of bone microstructure and disease-related abnormalities in multiple myeloma patients using a 1st-generation dual-source photon-counting detector CT(DS-PCD-CT) and a 2nd-generation dual-source dual-energy (energy-integrating detector) CT (DS-EID-CT). METHODS: Fifty multiple myeloma patients (mean age 67.7 ± 10.9 years,16 females) were prospectively enrolled. Unenhanced whole-body CTs were clinically indicated and performed on DS-EID-CT and DS-PCD-CT (median time difference: 12 months). DS-PCD-CT was performed in Quantumplus UHR mode and DS-EID-CT was performed using dual-energy mode. DS-PCD-CT kernel was set at Br64 with Quantum iterative reconstruction strength Q1; for DS-EID-CT a comparable I70f kernel with SAFIRE iterative reconstruction strength 1 was used. Two independent radiologists assessed image quality subjectively using a 5-point Likert scale considering delineation and sharpness of trabecular bone and lytic bone lesions in the spine and pelvic bones. Additionally, ImageJ was used for quantification of bony septa inside the cancellous bone and through or the edges of osteolysis. RESULTS: Overall quality as well as detectability and sharpness in the delineation of lytic bone lesions were superior for DS-PCD-CT compared with DS-EID-CT (p < 0.0001). The inter-reader agreement for subjective image quality readings showed excellent consistency(α = 94.2-98.8). CTDI and DLP mean values for DS-PCD-CT and DS-EID-CT were 1107.4 ± 247.6 mGy*cm and 8.2 ± 1.8 mGy vs. 1344.3 ± 204.6 mGy*cm and 10.1 ± 1.9 mGy. The quantitative metric for bone microstructure in the femoral head showed significantly better visualization of trabeculae in DS-PCD-CT compared with DS-EID-CT (p < 0.0001). Quantitative analyses of edge sharpness of osteolysis showed significant steeper edges for DS-PCD-CT (p < 0.0001). CONCLUSION: DS-PCD-CT significantly improves spatial resolution of bony microstructure and lytic bone lesions compared to DS-EID-CT. KEY POINTS: • Application of photon-counting detector CT is superior to dual-source dual-energy integrating detector in clinical workup of multiple myeloma patients. • Compared to energy integrating detectors, photon-counting detectors significantly increase the spatial resolution of bone microstructure including disease-related lytic bone lesions in patients with multiple myeloma.

CD19-Targeting CAR T Cells for Myositis and Interstitial Lung Disease Associated With Antisynthetase Syndrome.

Importance: Autoimmune disorders can affect various organs and if refractory, can be life threatening. Recently, CD19-targeting-chimeric antigen receptor (CAR) T cells were efficacious as an immune suppressive agent in 6 patients with refractory systemic lupus erythematosus and in 1 patient with antisynthetase syndrome. Objective: To test the safety and efficacy of CD19-targeting CAR T cells in a patient with severe antisynthetase syndrome, a complex autoimmune disorder with evidence for B- and T-cell involvement. Design, Setting, and Participants: This case report describes a patient with antisynthetase syndrome with progressive myositis and interstitial lung disease refractory to available therapies (including rituximab and azathioprine), who was treated with CD19-targeting CAR T cells in June 2022 at University Hospital Tübingen in Tübingen, Germany, with the last follow-up in February 2023. Mycophenolate mofetil was added to the treatment to cotarget CD8+ T cells, hypothesized to contribute to disease activity. Exposure: Prior to treatment with CD19-targeting CAR T cells, the patient received conditioning therapy with fludarabine (25 mg/m2 [5 days before until 3 days before]) and cyclophosphamide (1000 mg/m2 [3 days before]) followed by infusion of CAR T cells (1.23×106/kg [manufactured by transduction of autologous T cells with a CD19 lentiviral vector and amplification in the CliniMACS Prodigy system]) and mycophenolate mofetil (2 g/d) 35 days after CD19-targeting CAR T-cell infusion. Main Outcomes and Measures: The patient's response to therapy was followed by magnetic resonance imaging of the thigh muscle, Physician Global Assessment, functional muscle and pulmonary tests, and peripheral blood quantification of anti-Jo-1 antibody levels, lymphocyte subsets, immunoglobulins, and serological muscle enzymes. Results: Rapid clinical improvement was observed after CD19-targeting CAR T-cell infusion. Eight months after treatment, the patient's scores on the Physician Global Assessment and muscle and pulmonary function tests improved, and there were no detectable signs of myositis on magnetic resonance imaging. Serological muscle enzymes (alanine aminotransferase, aspartate aminotransferase, creatinine kinase, and lactate dehydrogenase), CD8+ T-cell subsets, and inflammatory cytokine secretion in the peripheral blood mononuclear cells (interferon gamma, interleukin 1 [IL-1], IL-6, and IL-13) were all normalized. Further, there was a reduction in anti-Jo-1 antibody levels and a partial recovery of IgA (to 67% of normal value), IgG (to 87%), and IgM (to 58%). Conclusions and Relevance: CD19-targeting CAR T cells directed against B cells and plasmablasts deeply reset B-cell immunity. Together with mycophenolate mofetil, CD19-targeting CAR T cells may break pathologic B-cell, as well as T-cell responses, inducing remission in refractory antisynthetase syndrome.

A data management infrastructure for the integration of imaging and omics data in life sciences.

BACKGROUND: As technical developments in omics and biomedical imaging increase the throughput of data generation in life sciences, the need for information systems capable of managing heterogeneous digital assets is increasing. In particular, systems supporting the findability, accessibility, interoperability, and reusability (FAIR) principles of scientific data management. RESULTS: We propose a Service Oriented Architecture approach for integrated management and analysis of multi-omics and biomedical imaging data. Our architecture introduces an image management system into a FAIR-supporting, web-based platform for omics data management. Interoperable metadata models and middleware components implement the required data management operations. The resulting architecture allows for FAIR management of omics and imaging data, facilitating metadata queries from software applications. The applicability of the proposed architecture is demonstrated using two technical proofs of concept and a use case, aimed at molecular plant biology and clinical liver cancer research, which integrate various imaging and omics modalities. CONCLUSIONS: We describe a data management architecture for integrated, FAIR-supporting management of omics and biomedical imaging data, and exemplify its applicability for basic biology research and clinical studies. We anticipate that FAIR data management systems for multi-modal data repositories will play a pivotal role in data-driven research, including studies which leverage advanced machine learning methods, as the joint analysis of omics and imaging data, in conjunction with phenotypic metadata, becomes not only desirable but necessary to derive novel insights into biological processes.

Interindividual Comparison of Frequency-Selective Nonlinear Blending to Conventional CT for Detection of Focal Liver Lesions Using MRI as the Reference Standard.

BACKGROUND. Diagnosing liver lesions is challenging. CT is used for primary diagnosis, but its contrast resolution is limited. Investigating methods to improve detection of liver lesions is important. OBJECTIVE. The purpose of this study was to evaluate the effect of frequency-selective nonlinear blending on the detectability of liver lesions on CT. METHODS. A retrospective search yielded 109 patients with 356 malignant and benign liver lesions (191 principally diagnosed, 165 incidental findings) who underwent contrast-enhanced CT (CECT) in the portal venous phase and liver MRI between January 2012 and December 2017. Nonlinear blending was applied to CECT examinations, and three blinded readers independently rated the quality (5-point Likert scale) of randomly presented images. Focal lesions (n = 356) were evaluated for lesion identification and categorization to assess sensitivity. For 191 lesions (primary diagnosis), two readers evaluated CECT and nonlinear blending CT to compare lesion size and the accuracy of subjective measurements. A fourth reader performed ROI measurements for calculation of contrast-to-noise ratio (CNR), and a fifth reader reviewed MRI as the standard of reference. Statistics included interobserver agreement, quantitative comparisons of CNR, lesion size, and subjective image analyses of image quality and sensitivity for detecting liver lesions. RESULTS. Three readers rated the image quality of nonlinear blending CT (rating, 4; 10th-90th percentiles, 4-5) higher than that of CECT (rating, 2; 10th-90th percentiles, 1-3) (p < .001). CECT had good interreader agreement (interclass correlation coefficient [ICC], 0.81; 95% CI, 0.76-0.85), as did nonlinear blending CT (ICC, 0.75; 95% CI, 0.69-0.79). The median CNR of liver lesions increased with nonlinear blending (CECT, 4.18 [10th-90th percentiles, 1.67-9.06]; nonlinear blending CT, 12.49 [10th-90th percentiles, 6.18-23.39]; p < .001). Bland-Altman analysis of lesion size showed a reduction in underestimation from 2.5 (SD, 9.2) mm (95% CI, 1.2-3.9 mm) with CECT to 0.1 (SD, 3.9) mm (95% CI, -0.68 to 0.46 mm) for nonlinear blending CT (concordance correlation coefficient, 0.99). Sensitivity for detecting liver lesions increased to 86% for nonlinear blending CT. The sensitivity of CECT was 76%. CONCLUSION. Frequency-selective nonlinear blending in CECT increases image quality and CNR, increases the precision of size measurement, and increases sensitivity for detecting liver lesions. CLINICAL IMPACT. Use of nonlinear blending CT improves liver lesion detection and increases the accuracy of lesion size measurement, which is important when local ablation or liver transplant is being considered.

Role of computed tomography texture analysis using dual-energy-based bone marrow imaging for multiple myeloma characterization: comparison with histology and established serologic parameters.

OBJECTIVE: To identify textural features on dual-energy CT (DECT)-based bone marrow images in myeloma which correlate with serum markers of myeloma activity and the degree of medullary involvement. METHODS: A total of 110 patients (63.0 ± 11.0 years, 51 female) who underwent unenhanced whole-body DECT between September 2015 and February 2019 were retrospectively included, which was approved by our institutional ethics committee with a waiver of the informed consent requirement. All patients had current hematologic laboratory tests. Using DECT post-processing, non-calcium bone marrow images were reconstructed. The vertebral bodies T10-L5 were segmented for quantification of textural features, which were compared with serologic parameters and myeloma stages by the Mann-Whitney U test. In a subgroup of 56/110 patients with current bone marrow biopsies, textural features were correlated with the degree of bone marrow infiltration. RESULTS: First-order features were higher in patients with advanced stage of myeloma (p < .02), whereas the 2nd-order "gray-level co-occurrence matrix (GLCM) cluster prominence" was lower (p < .04). In patients with elevated serum-free light chains (SFLC) or kappa/lambda SFLC ratio above 1.56, the "entropy" and 2nd-order GLCM features were lower (p < .03). The degree of bone marrow infiltration correlated with 1st-order features (e.g., "uniformity"; rP = 0.49; p < .0001), whereas "entropy" and 2nd-order GLCM features were negatively correlated (e.g., "difference entropy"; rP = - 0.54; p < .0001). CONCLUSIONS: CT textural features applied on non-calcium bone marrow images correlate well with myeloma-related serologic parameters and histology showing a more uniform tissue structure and higher attenuation with increasing medullary infiltration and could therefore be used as additional imaging biomarkers for non-invasive assessment of medullary involvement. KEY POINTS: • Texture analysis applied on dual-energy reconstructed non-calcium bone marrow images provides information about marrow structure and attenuation. • Myeloma-related serologic parameters and the degree of myeloma cell infiltration correlate with 1st- and 2nd-order features which could be useful as additional imaging biomarkers for non-invasive assessment of medullary involvement.

Transbronchial cryobiopsy increases diagnostic confidence in interstitial lung disease: a prospective multicentre trial.

INTRODUCTION: The accurate diagnosis of individual interstitial lung diseases (ILD) is often challenging, but is a critical determinant of appropriate management. If a diagnosis cannot be made after multidisciplinary team discussion (MDTD), surgical lung biopsy is the current recommended tissue sampling technique according to the most recent guidelines. Transbronchial lung cryobiopsy (TBLC) has been proposed as an alternative to surgical lung biopsy. METHODS: This prospective, multicentre, international study analysed the impact of TBLC on the diagnostic assessment of 128 patients with suspected idiopathic interstitial pneumonia by a central MDTD board (two clinicians, two radiologists, two pathologists). The level of confidence for the first-choice diagnoses were evaluated in four steps, as follows: 1) clinicoradiological data alone; 2) addition of bronchoalveolar lavage (BAL) findings; 3) addition of TBLC interpretation; and 4) surgical lung biopsy findings (if available). We evaluated the contribution of TBLC to the formulation of a confident first-choice MDTD diagnosis. RESULTS: TBLC led to a significant increase in the percentage of cases with confident diagnoses or provisional diagnoses with high confidence (likelihood ≥70%) from 60.2% to 81.2%. In 32 out of 52 patients nondiagnostic after BAL, TBLC provided a diagnosis with a likelihood ≥70%. The percentage of confident diagnoses (likelihood ≥90%) increased from 22.7% after BAL to 53.9% after TBLC. Pneumothoraces occurred in 16.4% of patients, and moderate or severe bleeding in 15.7% of patients. No deaths were observed within 30 days. INTERPRETATION: TBLC increases diagnostic confidence in the majority of ILD patients with an uncertain noninvasive diagnosis, with manageable side-effects. These data support the integration of TBLC into the diagnostic algorithm for ILD.

Predictive performance of the mHAP-II score in a real-life western cohort with hepatocellular carcinoma following trans-arterial chemoembolisation with drug-eluting beads (DEB-TACE).

OBJECTIVES: To evaluate the predictive performance of the modified hepatoma arterial embolisation prognostic II (mHAP-II) score in a real-life western hepatocellular carcinoma (HCC) cohort treated with drug-eluting bead-TACE and compare the mHAP-II with other scores in this cohort. METHODS: One hundred seventy-nine HCC patients (mean age 77 (± 9) years, 87% male) with one or more drug-eluting bead (DEB)-TACE sessions using 100-300 µm microspheres were retrospectively analysed. Performance analysis of the mHAP-II score was based on Mann-Whitney U tests, the Kaplan-Meier method, log-rank tests, receiver operating characteristics, Akaike's information criterion and Cox regression models. RESULTS: In this population, HCC risk factors were mainly alcohol abuse (31%) and hepatitis C (28%). The median survival of the entire cohort was 29.4 months. mHAP-II classification of the cohort was mHAP-II B (30%), C (41%) and D (23%) respectively. Survival of all subgroups differed significantly from each other (each p < 0.05). Area under the curve for receiver operating characteristic was 0.60 and Akaike's information criterion was 21.8 (p = 0.03), indicating a superior performance of mHAP-II score compared with HAP score and BCLC. Tumour number ≥ two (HR 1.54), alpha-fetoprotein > 400 µg/l (HR 1.14), serum albumin < 3.6 g/dl (HR 1.63) and total bilirubin > 0.9 mg/dl (HR 1.58) contributed significantly in Cox proportional hazards regression (each p < 0.05). CONCLUSION: The mHAP-II score can predict survival outcomes of western HCC patients undergoing DEB-TACE and further subdivide this heterogeneous group; however, certain limitations concerning the predictive power of mHAP-II score must be taken into account. KEY POINTS: • This retrospective study evaluated the predictive performance of the modified hepatoma arterial embolisation prognostic II (mHAP-II) score in a real-life western HCC cohort treated with drug-eluting bead-TACE. • Survival of all mHAP-II subgroups differed significantly, area under the curve for mHAP-II was 0.60 and Akaike's information criterion was 21.8. • The mHAP-II score can predict survival outcomes of western HCC patients undergoing DEB-TACE and further subdivide this heterogeneous group. However, because the study is underpowered, true survival prediction may be more difficult to infer.

Use of 3-D navigation to target the site of autologous blood installation for lung volume reduction in bullous emphysema.

Bronchoscopic lung volume reduction (BLVR) using intrabullous autologous blood instillation has been reported in single cases where other techniques are not possible. We present the use of three-dimensional navigation to instill autologous blood into emphysematous bullae for BLVR. A 62-year-old man presented with increasing dyspnea, due to emphysema with a conglomerate of giant bullae with two particularly large bullae. Surgical treatment was refused, so bronchoscopic autologous blood instillation into the bronchial segment leading to the large bullae was attempted, but was unsuccessful; blood failed to penetrate into the bullous cavity. Dyspnea worsened over the following year. We therefore performed another bronchoscopy and punctured a large bulla with a needle and created a tunnel from the central airways. Puncture position and direction were determined using a prototype of an electromagnetic navigation system. Under fluoroscopic guidance, a catheter was placed via the tunnel into the bulla and blood was instilled. This resulted in an almost complete shrinkage of the bullae, reduction of residual volume, and marked improvement in dyspnea within 4 months. To our knowledge, this is the first reported case of successful BLVR by navigated bronchoscopy with transbronchial puncture, dilatation, and autologous blood instillation into a giant bulla.

A multiscale modelling approach to assess the impact of metabolic zonation and microperfusion on the hepatic carbohydrate metabolism.

The capacity of the liver to convert the metabolic input received from the incoming portal and arterial blood into the metabolic output of the outgoing venous blood has three major determinants: The intra-hepatic blood flow, the transport of metabolites between blood vessels (sinusoids) and hepatocytes and the metabolic capacity of hepatocytes. These determinants are not constant across the organ: Even in the normal organ, but much more pronounced in the fibrotic and cirrhotic liver, regional variability of the capillary blood pressure, tissue architecture and the expression level of metabolic enzymes (zonation) have been reported. Understanding how this variability may affect the regional metabolic capacity of the liver is important for the interpretation of functional liver tests and planning of pharmacological and surgical interventions. Here we present a mathematical model of the sinusoidal tissue unit (STU) that is composed of a single sinusoid surrounded by the space of Disse and a monolayer of hepatocytes. The total metabolic output of the liver (arterio-venous glucose difference) is obtained by integration across the metabolic output of a representative number of STUs. Application of the model to the hepatic glucose metabolism provided the following insights: (i) At portal glucose concentrations between 6-8 mM, an intra-sinusoidal glucose cycle may occur which is constituted by glucose producing periportal hepatocytes and glucose consuming pericentral hepatocytes, (ii) Regional variability of hepatic blood flow is higher than the corresponding regional variability of the metabolic output, (iii) a spatially resolved metabolic functiogram of the liver is constructed. Variations of tissue parameters are equally important as variations of enzyme activities for the control of the arterio-venous glucose difference.

Can contrast-enhanced ultrasound and acoustic radiation force impulse imaging characterize CT-indeterminate renal masses? A prospective evaluation with histological confirmation.

PURPOSE: To prospectively characterize computed tomography (CT)-indeterminate renal masses (CTIRM) using acoustic radiation force impulse (ARFI) elastography and contrast-enhanced ultrasound (CEUS) and to correlate quantitative imaging findings with histopathology or interim follow-up (FU). METHODS: 123 patients with CTIRM (longest diameter < 4 cm) underwent ARFI and CEUS with CT image fusion (IF). Exclusion criteria included all contraindications for CEUS and IF. Shear wave velocity (SWV), shear wave ratio (SWR), peak intensity (PE), time to peak (TTP) and wash-in rate (Wi) were quantified. In case of a cystic lesion classified as ≤ Bosniak 2F, follow-up imaging was performed. RESULTS: 77 out of 123 patients underwent surgical resection of a lesion due to suspect imaging findings, whereas 46 patients underwent FU, which did not show upgrading in Bosniak category. Histopathology revealed 58 renal cell carcinomas [five chromophobe (chRCC), 18 papillary (pRCC) and 35 clear cell (ccRCC)], ten oncocytomas and nine non-malignant renal lesions (one minimal fat AML, three focal nephritis and five infected cysts). SWV and SWR differed significantly between ccRCC, pRCC, chRCC (p = 0.0024, F = 13.94) and in SWR also for oncocytoma (p < 0.0001, F = 14.35). In CEUS, oncocytoma and ccRCC showed significant higher PE values (p < 0.0001, F = 77.31) as well as higher Wi and lower TTP compared to all other solid lesions. CONCLUSIONS: Quantitative CEUS and ARFI imaging can provide relevant information to further characterize CT-indeterminate renal masses to guide urological decision making and offer the possibility of differentiation between ccRCC from less malignant RCC subtypes and from oncocytoma.

Diagnosis of diffuse spleen involvement in haematological malignancies using a spleen-to-liver attenuation ratio on contrast-enhanced CT images.

OBJECTIVES: We aimed to test the hypothesis that the spleen-to-liver-attenuation ratio on portal-venous enhancement phase CT images can identify diffuse splenic infiltration in subjects with lymphoma. METHODS: A database search yielded 70 subjects with malignant haematological diseases who underwent contrast-enhanced CT (CECT) between December 2010 and March 2018. Additionally, consecutive control subjects were evaluated. We compared the splenic volume, splenic attenuation, spleen-to-liver, spleen-to-aorta and spleen-to-musculature ratios on portal-venous phase CECT images, pre- to post-treatment and between the different lymphoma entities. The standard of reference for splenic involvement was normalisation of the spleen volume following chemotherapy or normalisation of FDG-uptake. RESULTS: In subjects with diffuse splenic involvement, the spleen attenuation was significantly lower before treatment (93.48 HU) compared to controls (112.39 HU; p < .01) and after successful treatment (113.39 HU; p < .01). The spleen-to-liver attenuation ratio significantly increased after treatment (p < .001) and proved significantly lower at baseline when compared to control subjects (p < .01). The spleen volume significantly decreased after successful treatment (from 586.14.87 cm3 to 284.90 cm3; p < .001). Spleen-to-liver ratio significantly increased in lymphoma patients after therapy, inversely correlating with the decline in FDG-uptake (n=10) even in patients with normal-sized spleens (2/10), staying unchanged at follow-up. The outcome variables were not significantly different between the lymphoma subtypes. CONCLUSIONS: We suggest the additional use of spleen-to-liver attenuation ratio to splenic volume alone for detection of diffuse splenic infiltration in subjects with lymphoma. The course of spleen-to-liver attenuation ratio inversely correlated with that of FDG-uptake in a subgroup of patients working accurately in normal-sized diffusely involved spleens. KEY POINTS: • Involvement of the spleen is frequent in haematological malignancies and is important for staging and appropriate treatment. • Diffuse splenic infiltration often results in only homogeneous splenomegaly without a focal lesion, but even no or only minimal increase in splenic volume is possible. In these cases diagnosis of spleen involvement is a challenge for the radiologist. • Our data support the use of the spleen-to-liver attenuation ratio in addition to size measurements for the detection of diffuse splenic infiltration in subjects with lymphoma.

Dual-energy CT for liver iron quantification in patients with haematological disorders.

OBJECTIVES: To retrospectively quantify liver iron content in haematological patients suspected of transfusional haemosiderosis using dual-energy CT (DECT) and correlate with serum ferritin levels and estimated quantity of transfused iron. METHODS: One hundred forty-seven consecutive dual-source dual-energy non-contrast chest-CTs in 110 haematologic patients intended primarily for exclusion of pulmonary infection between September 2016 and June 2017 were retrospectively evaluated. Image data was post-processed with a software prototype. After material decomposition, an iron enhancement map was created and freehand ROIs were drawn including most of the partially examined liver. The virtual iron content (VIC) was calculated and expressed in milligram/millilitre. VIC was correlated with serum ferritin and estimated amount of transfused iron. Scans of patients who had not received blood products were considered controls. RESULTS: Forty-eight (32.7%) cases (controls) had not received any blood transfusions whereas 67.3% had received one transfusion or more. Median serum ferritin and VIC were 138.0 µg/dl (range, 6.0-2628.0 µg/dl) and 1.33 mg/ml (range, - 0.94-7.56 mg/ml) in the post-transfusional group and 27.0 µg/dl (range, 1.0-248.0 µg/dl) and 0.61 mg/ml (range, - 2.1-2.4) in the control group. Correlation between serum ferritin and VIC was strong (r = 0.623; p < 0.001) as well as that between serum ferritin and estimated quantity of transfused iron (r = 0.681; p < 0.001). CONCLUSIONS: Hepatic VIC obtained via dual-energy chest-CT examinational protocol strongly correlates with serum ferritin levels and estimated amount of transfused iron and could therefore be used in the routine diagnosis for complementary evaluation of transfusional haemosiderosis. KEY POINTS: • Virtual liver iron content was measured in routine chest-CTs of haematological patients suspected of having iron overload. Chest-CTs were primarily intended for exclusion of pulmonary infection. • Measurements correlate strongly with the most widely used blood marker of iron overload serum ferritin (after exclusion of infection) and the amount of transfused iron. • Liver VIC could be used for supplemental evaluation of transfusional haemosiderosis in haematological patients.

Transarterial Chemoembolization of Hepatocellular Carcinoma Using Radiopaque Drug-Eluting Embolics: How to Pursue Periprocedural Cross-Sectional Imaging?

PURPOSE: To compare different imaging techniques (volume perfusion CT, cone-beam CT, and dynamic gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced dynamic contrast-enhanced MR imaging with golden-angle radial sparse parallel MR imaging) in evaluation of transarterial chemoembolization of hepatocellular carcinoma (HCC) using radiopaque drug-eluting embolics (DEE). MATERIALS AND METHODS: MR imaging and CT phantom investigation of radiopaque DEE was performed. In the clinical portion of the study, 13 patients (22 HCCs) were prospectively enrolled. All patients underwent cross-sectional imaging before and after transarterial chemoembolization using 100-300 µm radiopaque DEE. Qualitative assessment of images using a Likert scale was performed. RESULTS: In the phantom study, CT-related beam-hardening artifacts were markedly visible at a concentration of 12% (v/v) radiopaque DEE; MR imaging demonstrated no significant detectable signal intensity changes. Imaging obtained before transarterial chemoembolization showed no significant difference regarding tumor depiction. Visualization of tumor feeding arteries was significantly improved with volume perfusion CT (P < .001) and cone-beam CT (P = .002) compared with MR imaging. Radiopaque DEE led to significant decrease in tumor depiction (P = .001) and significant increase of beam-hardening artifacts (P = .012) using volume perfusion CT before versus after transarterial chemoembolization. Greater residual arterial tumor enhancement was detected with MR imaging (10 HCCs) compared with volume perfusion CT (8 HCCs) and cone-beam CT (6 HCCs). CONCLUSIONS: Using radiopaque DEE, the imaging modalities provided comparable early treatment assessment. In HCCs with dense accumulation of radiopaque DEE, treatment assessment using volume perfusion CT or cone-beam CT may be impaired owing to resulting beam-hardening artifacts and contrast stasis. Dynamic contrast-enhanced MR imaging may add value in detection of residual arterial tumor enhancement.

Comprehensive metabolic and morphologic disease characterization in systemic sclerosis: initial results using combined positron emission tomography and magnetic resonance imaging.

BACKGROUND: The aim of this study was to evaluate the role of metabolic and morphologic parameters derived from simultaneous hybrid PET/MRI in correlation to clinical criteria for an image-based characterization of musculoskeletal, esophagus and lymph node involvement in systemic sclerosis (SSc). METHODS: Between November 2013 and May 2015, simultaneous whole-body hybrid PET/MRI was performed in 13 prospectively recruited patients with SSc. A mean dose of 241.3 MBq 2-deoxy-2-[18F]fluoro-D-glucose (FDG) was injected. SUVmean and SUVmax values were measured in the spinal bone marrow, spleen, joints, muscles, fasciae, mediastinal lymph nodes and esophagus. MRI abnormalities were scored as 0 (absent), 1 (moderate) and 2 (marked). In addition, organ and skin involvement were graded with clinical sum score (CSS) and modified Rodnan skin score (mRSS), respectively. RESULTS: Results indicate positive correlations between mRSS and fascial FDG-uptake values (fascia summed SUVmax ρ=0.67; fascia summed SUVmean ρ=0.66) that performed better than the MRI sum score (ρ=0.50). Fascial FDG-uptake is also useful in the differentiation between diffuse and limited SSc. Additionally, FDG-PET detected patients with active mediastinal lymphadenopathy and MRI proved to be useful for the delineation of esophagus involvement. CONCLUSIONS: Fascial FDG-uptake has a strong correlation with mRSS and can discriminate between limited and diffuse SSc. These results and the detection of active lymphadenopathy and esophagus involvement can identify patients with advanced scleroderma. Combined PET/MRI therefore provides complementary information on the complex pathophysiology and may integrate several imaging procedures in one.

Potential role of CT-textural features for differentiation between viral interstitial pneumonias, pneumocystis jirovecii pneumonia and diffuse alveolar hemorrhage in early stages of disease: a proof of principle.

BACKGROUND: Pulmonary involvement is common in several infectious and non-infectious diagnostic settings. Imaging findings consistently overlap and are therefore difficult to differentiate by chest-CT. The aim of this study was to evaluate the role of CT-textural features(CTTA) for discrimination between atypical viral (respiratory-syncitial-virus(RSV) and herpes-simplex-1-virus (HSV1)), fungal (pneumocystis-jirovecii-pneumonia(PJP)) interstitial pneumonias and alveolar hemorrhage. METHODS: By retrospective single-centre analysis we identified 46 consecutive patients (29 m) with RSV(n = 5), HSV1(n = 6), PJP(n = 21) and lung hemorrhage(n = 14) who underwent unenhanced chest CTs in early stages of the disease between 01/2016 and 02/2017. All cases were confirmed by microbiologic direct analysis of bronchial lavage. On chest-CT-scans, the presence of imaging features like ground-glass opacity(GGO), crazy-paving, air-space consolidation, reticulation, bronchial wall thickening and centrilobular nodules were described. A representative large area was chosen in both lungs and used for CTTA-parameters (included heterogeneity, intensity, average, deviation, skewness). RESULTS: Discriminatory CTTA-features were found between alveolar hemorrhage and PJP consisting of differences in mean heterogeneity(p < 0.015) and uniformity of skewness(p < 0.006). There was no difference between CT-textural features of diffuse alveolar hemorrhage and viral pneumonia or PJP and viral pneumonia. Visual HRCT-assessment yielded great overlap of imaging findings with predominance of GGO for PJP and airspace consolidation for pneumonia/alveolar hemorrhage. Significant correlations between HRCT-based imaging findings and CT-textural features were found for all three disease groups. CONCLUSION: CT-textural features showed significant differences in mean heterogeneity and uniformity of skewness. HRCT-based imaging findings correlated with certain CT-textural features showing that the latter have the potential to characterize structural properties of lung parenchyma and related abnormalities.

Intermetatarsal bursitis as first disease manifestation in different rheumatological disorders and related MR-imaging findings.

Metatarsalgia defined as pain at the plantar aspect of the forefoot. Intermetatarsal bursitis is considered one potential soft-tissue cause of metatarsalgia that is presumably under-estimated, under-investigated, and, consequently, often misdiagnosed. To assess the role of MRI in the elucidation of the cause of metatarsalgia in patients with different autoimmune disorders presenting primarily with this symptom and to present the accompanying clinical and radiological findings of intermetatarsal bursitis. Retrospective evaluation of the medical records of patients with different rheumatological conditions claiming primarily of pedal pains suggests metatarsalgia and who underwent, therefore, all magnetic resonance imaging between March 2010 and April 2018. Of them, six patients fulfilled these criteria and were diagnosed subsequently with intermetatarsal bursitis. Several underlying autoimmune conditions were diagnosed. All patients were clinically assessed by the squeeze test and radiologically investigated with MRI; three patients underwent additional sonography. All patients presented intermetatarsal bursitis as first disease manifestation. The number of involved bursae ranged from one to three on one side. The main MR findings were distension of the intermetatarsal bursa with increased signal intensity on T2-weighted and post-contrast fat saturation T1-weighted images. Most frequent locations were the second and third intermetatarsal spaces. The size of the intermetatarsal bursitis and its plantar extension were correlated in all patients. Intermetatarsal bursitis can potentially be the first manifestation of different rheumatological diseases. Awareness of this potential association as well as cognizance of its imaging findings can help for making a more accurate and prompt earlier diagnosis of the underlying disease changing also the therapeutic approach.

Contrast-enhanced imaging in hepatic epithelioid hemangioendothelioma: retrospective study of 10 patients.

PURPOSE: The purpose of this study was to analyze imaging findings in hepatic epithelioid hemangioendothelioma (HEHE) with a particular focus on contrast-enhanced ultrasound (CEUS). MATERIALS AND METHODS: This retrospective multicenter study included 10 patients with histologically proven HEHE from 5 European centers. All existing ultrasound images/videos were independently analyzed by 2 experienced examiners (DEGUM level III, internal medicine) using a standardized evaluation form. Patterns of contrast enhancement were correlated with computed tomography (CT), magnetic resonance imaging (MRI), and pathological findings. RESULTS: B-mode ultrasound, CEUS, CT, and MRI were performed in 90 %, 70 %, 100 %, and 90 % of patients, respectively. Multifocal HEHE could be observed in 80 % with affection of both liver lobes in 70 %. Analysis of CEUS revealed 3 characteristic patterns that correlated well with contrast patterns on CT and MRI: (a) peripheral nodular enhancement with centripetal fill-in and wash-out in the portal venous and late venous phase (PVLP), (b) rim-like arterial enhancement with wash-out in the PVLP, and (c) inversed target sign with/without wash-out in the PVLP. Wash-out in the PVLP as a sign suspicious of malignancy was observed in 6/7 patients (85.7 %). CONCLUSIONS: Knowledge of the different characteristic CEUS patterns is of importance to avoid misdiagnosis due to resemblance of patterns A and B to the much more common focal liver lesions hemangioma and intrahepatic cholangiocarcinoma. Of importance, sonographers should be aware that wash-out in the PVLP might be absent in some patients.

Diagnosis of Richter transformation in chronic lymphocytic leukemia: histology tips the scales.

Development of diffuse large B-cell lymphoma in chronic lymphocytic leukemia, so-called Richter transformation (RT), occurs in 2-5% of patients and is associated with poor outcome. The clinical features of RT are fairly non-specific and unable to discriminate transformation from other mimics. In case of clinically suspected RT, a CT/MRT is recommended, and FDG-PET/CT may help to select the site of biopsy. Radiological features suggestive of RT have been defined, but there are only limited data about their predictive value, and histological confirmation is still considered the gold standard for RT diagnosis. We retrospectively analyzed 34 patients with clinically suspected RT and available radiological and histological data. A histopathological diagnosis of RT with concordant clinical and radiological findings was obtained in 13 patients. In 18 patients, CT did not show features of transformation, concordant with lack of RT in the biopsy. Of interest, a distinct lymphoma other than DLBCL was identified in two of these cases. A false-positive radiological diagnosis of RT was rendered in two patients, including a case of Herpes simplex virus lymphadenitis. In conclusion, our findings confirm the central role of tissue biopsy in the diagnostic work up in case of clinically suspected RT.

Diagnosis of invasive fungal diseases in haematology and oncology: 2018 update of the recommendations of the infectious diseases working party of the German society for hematology and medical oncology (AGIHO).

Invasive fungal diseases (IFD) are a primary cause of morbidity and mortality in patients with haematological malignancies. These infections are mostly life-threatening and an early diagnosis and initiation of appropriate antifungal therapy are essential for the clinical outcome. Most commonly, Aspergillus and Candida species are involved. However, other Non-Aspergillus moulds are increasingly identified in case of documented IFD. For definite diagnosis of IFD, a combination of diagnostic tools have to be applied, including conventional mycological culture and non-conventional microbiological tests such as antibody/antigen and molecular tests, as well as histopathology and radiology. Although varying widely in cancer patients, the risk of invasive fungal infection is highest in those with allogeneic stem cell transplantation and those with acute leukaemia and markedly lower in patients with solid cancer. Since the last edition of Diagnosis of Invasive Fungal Diseases recommendations of the German Society for Hematology and Oncology in 2012, integrated care pathways have been proposed for the management and therapy of IFDs with either a diagnostic driven strategy as opposed to a clinical or empirical driven strategy. This update discusses the impact of this additional evidence and effective revisions.

Prognostic value of perfusion CT in hepatocellular carcinoma treatment with sorafenib: comparison with mRECIST in longitudinal follow-up.

Background Targeted therapies are of increasing clinical importance and classic radiologic therapy response-criteria often fail to detect early therapeutic response or failure. For hepatocellular carcinoma (HCC), this is of major importance as therapeutic options are limited. Purpose To investigate the impact of sorafenib-treatment on intralesional perfusion using perfusion computed tomography (PCT) in HCC and to correlate the observed changes with mRECIST and the course of serum alpha-fetoprotein (AFP) for identification of their prognostic value. Material and Methods PCT was performed before and after two months of sorafenib treatment in 28 consecutive HCC patients and AFP levels were registered. Changes in tumor perfusion parameters blood flow (BF), blood volume (BV), mean transit time (MTT), volume transfer constant (Ktrans), arterial liver perfusion (ALP), and hepatic perfusion index (HPI) were registered in one target lesion. mRECIST measurements were performed at baseline and after two and four months during sorafenib treatment. Results According to mRECIST, after two months of treatment, all patients showed stable disease (SD), whereas after four months, 13 patients (46%) showed SD and 15 patients (54%) showed progressive disease (PD). A significant decrease was found in perfusion parameters BF, BV, Ktrans, ALP, and HPI in patients with SD as well as a significant increase in MTT ( P < 0.05) after two months compared to baseline, while patients with PD showed a significant increase in HPI, BF, and BV. There were no correlations between AFP and mRECIST or perfusion parameters. Conclusion Decreased intralesional BF and HPI after two months of sorafenib treatment predicts disease stabilization after four months, whereas AFP dynamics were of limited value.