CD200+ fibroblasts form a pro-resolving mesenchymal network in arthritis.

Fibroblasts are important regulators of inflammation, but whether fibroblasts change phenotype during resolution of inflammation is not clear. Here we use positron emission tomography to detect fibroblast activation protein (FAP) as a means to visualize fibroblast activation in vivo during inflammation in humans. While tracer accumulation is high in active arthritis, it decreases after tumor necrosis factor and interleukin-17A inhibition. Biopsy-based single-cell RNA-sequencing analyses in experimental arthritis show that FAP signal reduction reflects a phenotypic switch from pro-inflammatory MMP3+/IL6+ fibroblasts (high FAP internalization) to pro-resolving CD200+DKK3+ fibroblasts (low FAP internalization). Spatial transcriptomics of human joints indicates that pro-resolving niches of CD200+DKK3+ fibroblasts cluster with type 2 innate lymphoid cells, whereas MMP3+/IL6+ fibroblasts colocalize with inflammatory immune cells. CD200+DKK3+ fibroblasts stabilized the type 2 innate lymphoid cell phenotype and induced resolution of arthritis via CD200-CD200R1 signaling. Taken together, these data suggest a dynamic molecular regulation of the mesenchymal compartment during resolution of inflammation.

Highly accelerated, Dixon-based non-contrast MR angiography versus high-pitch CT angiography.

OBJECTIVES: To compare a novel, non-contrast, flow-independent, 3D isotropic magnetic resonance angiography (MRA) sequence that combines respiration compensation, electrocardiogram (ECG)-triggering, undersampling, and Dixon water-fat separation with an ECG-triggered aortic high-pitch computed tomography angiography (CTA) of the aorta. MATERIALS AND METHODS: Twenty-five patients with recent CTA were scheduled for non-contrast MRA on a 3 T MRI. Aortic diameters and cross-sectional areas were measured on MRA and CTA using semiautomatic measurement tools at 11 aortic levels. Image quality was assessed independently by two radiologists on predefined aortic levels, including myocardium, proximal aortic branches, pulmonary veins and arteries, and the inferior (IVC) and superior vena cava (SVC). Image quality was assessed on a 5-point Likert scale. RESULTS: All datasets showed diagnostic image quality. Visual grading was similar for MRA and CTA regarding overall image quality (0.71), systemic arterial image quality (p = 0.07-0.91) and pulmonary artery image quality (p = 0.05). Both readers favored MRA for SVC and IVC, while CTA was preferred for pulmonary veins (all p < 0.05). No significant difference was observed in aortic diameters or cross-sectional areas between native MRA and contrast-enhanced CTA (p = 0.08-0.94). CONCLUSION: The proposed non-contrast MRA enables robust imaging of the aorta, its proximal branches and the pulmonary arteries and great veins with image quality and aortic diameters and cross-sectional areas comparable to that of CTA. Moreover, this technique represents a suitable free-breathing alternative, without the use of contrast agents or ionizing radiation. Therefore, it is especially suitable for patients requiring repetitive imaging.

Assessment of myocardial fibrosis in patients with systemic sclerosis using [68Ga]Ga-FAPI-04-PET-CT.

PURPOSE: Myocardial fibrosis (MF) is a factor of poor prognosis in systemic sclerosis (SSc). Direct in-vivo visualization of fibroblast activation as early readout of MF has not been feasible to date. Here, we characterize 68Gallium-labeled-Fibroblast-Activation-Inhibitor-04 ([68Ga]Ga-FAPI-04)-PET-CT as a diagnostic tool in SSc-related MF. METHODS: In this proof-of-concept trial, six SSc patients with and eight without MF of the EUSTAR cohort Erlangen underwent [68Ga]Ga-FAPI-04-PET-CT and cardiac MRI (cMRI) and clinical and serologic investigations just before baseline and during follow-up between January 2020 and December 2020. Myocardial biopsy was performed as clinically indicated. RESULTS: [68Ga]Ga-FAPI-04 tracer uptake was increased in SSc-related MF with higher uptake in SSc patients with arrhythmias, elevated serum-NT-pro-BNP, and increased late gadolinium enhancement (LGE) in cMRI. Histologically, myocardial biopsies from cMRI- and [68Ga]Ga-FAPI-04-positive regions confirmed the accumulation of FAP+ fibroblasts surrounded by collagen deposits. We observed similar but not equal spatial distributions of [68Ga]Ga-FAPI-04 uptake and quantitative cMRI-based techniques. Using sequential [68Ga]Ga-FAPI-04-PET-CTs, we observed dynamic changes of [68Ga]Ga-FAPI-04 uptake associated with changes in the activity of SSc-related MF, while cMRI parameters remained stable after regression of molecular activity and rather indicated tissue damage. CONCLUSIONS: We present first in-human evidence that [68Ga]Ga-FAPI-04 uptake visualizes fibroblast activation in SSc-related MF and may be a diagnostic option to monitor cardiac fibroblast activity in situ.

Non-rigid motion-corrected free-breathing 3D myocardial Dixon LGE imaging in a clinical setting.

OBJECTIVES: To investigate the efficacy of an in-line non-rigid motion-compensated reconstruction (NRC) in an image-navigated high-resolution three-dimensional late gadolinium enhancement (LGE) sequence with Dixon water-fat separation, in a clinical setting. METHODS: Forty-seven consecutive patients were enrolled prospectively and examined with 1.5 T MRI. NRC reconstructions were compared to translational motion-compensated reconstructions (TC) of the same datasets in overall and different sub-category image quality scores, diagnostic confidence, contrast ratios, LGE pattern, and semiautomatic LGE quantification. RESULTS: NRC outperformed TC in all image quality scores (p < 0.001 to 0.016; e.g., overall image quality 5/5 points vs. 4/5). Overall image quality was downgraded in only 23% of NRC datasets vs. 53% of TC datasets due to residual respiratory motion. In both reconstructions, LGE was rated as ischemic in 11 patients and non-ischemic in 10 patients, while it was absent in 26 patients. NRC delivered significantly higher LGE-to-myocardium and blood-to-myocardium contrast ratios (median 6.33 vs. 5.96, p < 0.001 and 4.88 vs. 4.66, p < 0.001, respectively). Automatically detected LGE mass was significantly lower in the NRC reconstruction (p < 0.001). Diagnostic confidence was identical in all cases, with high confidence in 89% and probable in 11% datasets for both reconstructions. No case was rated as inconclusive. CONCLUSIONS: The in-line implementation of a non-rigid motion-compensated reconstruction framework improved image quality in image-navigated free-breathing, isotropic high-resolution 3D LGE imaging with undersampled spiral-like Cartesian sampling and Dixon water-fat separation compared to translational motion correction of the same datasets. The sharper depictions of LGE may lead to more accurate measures of LGE mass. KEY POINTS: • 3D LGE imaging provides high-resolution detection of myocardial scarring. • Non-rigid motion correction provides better image quality in cardiac MRI. • Non-rigid motion correction may lead to more accurate measures of LGE mass.

Cardiac T2 mapping: robustness and homogeneity of standardized in-line analysis.

BACKGROUND AND PURPOSE: Interpretation of T2 values remains difficult due to limited comparability across hardware and software systems and the lack of validated measurement recommendations for the number and orientation of mandatory slices. Our aims were to provide a standardized comparison of intra- and inter-individual T2 values in the short and long axes and to investigate inter-scanner reproducibility. METHOD AND MATERIALS: Ninety cardiovascular magnetic resonance (CMR) studies in 30 healthy subjects were performed with three identical 1.5 T CMR scanners (same hardware and software) using a balanced steady-state free precession (bSSFP) gradient echo sequence in three short axis (SAx) and three long axis (LAx) views. A commercially available T2 mapping software package of the latest generation with automatic in-line motion correction was used for acquisition. Regions of interest were manually drawn in each of the 16 myocardial segments according to the American Heart Association (AHA) model in three SAx and three LAx acquisitions. Analysis of inter-scanner, inter-segmental, intra-segmental, inter-regional and inter-level differences was performed. RESULTS: Inter-scanner reproducibility was high and the mean myocardial T2 value for all evaluated segments was 45.7 ± 3.4 ms. Significant inter-segmental variations of mean T2 values were found. Mean intra-segmental T2 values were comparable between LAx and SAx acquisitions in 72%. Significantly higher T2 values were found in apical segments and a significant disparity among different regions was found for SAx and LAx orientations. CONCLUSION: Standardized cardiac T2 mapping is highly reproducible on identical CMR systems. T2 values vary significantly between single heart segments, regions, levels, and axes in young, healthy subjects.

Dual-source computed tomography of the lung with spectral shaping and advanced iterative reconstruction: potential for maximum radiation dose reduction.

BACKGROUND: Radiation dose at CT should be as low as possible without compromising diagnostic quality. OBJECTIVE: To assess the potential for maximum dose reduction of pediatric lung dual-source CT with spectral shaping and advanced iterative reconstruction (ADMIRE). MATERIALS AND METHODS: We retrospectively analyzed dual-source CT acquisitions in a full-dose group (FD: 100 kV, 64 reference mAs) and in three groups with spectral shaping and differing reference mAs values (Sn: 100 kV, 96/64/32 reference mAs), each group consisting of 16 patients (age mean 11.5 years, standard deviation 4.8 years, median 12.8 years, range 1.3-18 years). Advanced iterative reconstruction of images was performed with different strengths (FD: ADMIRE Level 2; Sn: ADMIRE Levels 2, 3 and 4). We analyzed dose parameters and measured noise. Diagnostic confidence and detectability of lung lesions as well as anatomical structures were assessed using a Likert scale (from 1 [unacceptable] to 4 [fully acceptable]). RESULTS: Compared to full dose, effective dose was reduced to 16.7% in the Sn 96 group, 11.1% in Sn64, and 5.5% in Sn32 (P<0.001). Noise values of Sn64ADM4 did not statistically differ from those in FDADM2 (45.7 vs. 38.9 Hounsfield units [HU]; P=0.132), whereas noise was significantly higher in Sn32ADM4 compared to Sn64ADM4 (61.5 HU; P<0.001). A Likert score >3 was reached in Sn64ADM4 regarding diagnostic confidence (3.2) and detectability of lung lesions (3.3). For detectability of most anatomical structures, no significant differences were found between FDAM2 and Sn64ADM4 (P≥0.05). CONCLUSION: In pediatric lung dual-source CT, spectral shaping together with ADMIRE 4 enable radiation dose reduction to about 10% of a full-dose protocol while maintaining an acceptable diagnostic quality.

Comprehensive assessment of knee joint synovitis at 7 T MRI using contrast-enhanced and non-enhanced sequences.

BACKGROUND: Seven T ultra-high field MRI systems have recently been approved for clinical use by the U.S. and European regulatory agencies. These systems are now being used clinically and will likely be more widely available in the near future. One of the applications of 7 T systems is musculoskeletal disease and particularly peripheral arthritis imaging. Since the introduction of potent anti-rheumatic therapies over the last two decades MRI has gained increasing importance particularly for assessment of disease activity in early stages of several rheumatic disorders. Commonly gadolinium-based contrast agents are used for assessment of synovitis. Due to potential side-effects of gadolinium non-enhanced techniques are desirable that enable visualization of inflammatory disease manifestations. The feasibility of 7 T MRI for evaluation of peripheral arthritis has not been shown up to now. Aim of our study was to evaluate the feasibility of contrast-enhanced (CE) and non-enhanced MRI at 7 T for the assessment of knee joint synovitis. METHOD: Seven T MRI was acquired for 10 patients with an established diagnosis of psoriatic or rheumatoid arthritis. The study pulse sequence protocol was comprised of a sagittal intermediate-weighted fat-suppressed (FS), axial fluid-attenuated inversion recovery (FLAIR) FS, sagittal 3D T1-weighted dynamic contrast enhanced (DCE) and an axial static 2D T1-weighted FS contrast-enhanced sequence (T1-FS CE). Ordinal scoring on non-enhanced (Hoffa- and effusion-synovitis) and enhanced MRI (11-point synovitis score), and comparison of FLAIR-FS with static T1-FS CE MRI using semiquantitative (SQ) grading and volume assessment was performed. For inter- and intra-reader reliability assessment weighted kappa statistics for ordinal scores and intraclass correlation coefficients (ICC) for continuous variables were used. RESULTS: The total length of study protocol was 15 min 38 s. Different amounts of synovitis were observed in all patients (mild: n = 3; moderate: n = 5; severe: n = 2). Consistently, SQ assessment yielded significantly lower peripatellar summed synovitis scores for the FLAIR-FS sequence compared to the CE T1-FS sequence (p < 0.01). FLAIR-FS showed significantly lower peripatellar synovial volumes (p < 0.01) compared to CE T1-FS imaging with an average percentage difference of 18.6 ± 9.5%. Inter- and intra-reader reliability for ordinal SQ scoring ranged from 0.21 (inter-reader Hoffa-synovitis) to 1.00 (inter-reader effusion-synovitis). Inter- and intra-observer reliability of SQ 3D-DCE parameters ranged from 0.86 to 0.99. CONCLUSIONS: Seven T FLAIR-FS ultra-high field MRI is a potential non-enhanced imaging method able to visualize synovial inflammation with high conspicuity and holds promise for further application in research endeavors and clinical routine by trained readers.

Streptococcal toxic shock syndrome with associated necrotising fasciitis necessitating amputation of the lower extremity - A case report.

Streptococcal toxic shock syndrome is a severe, invasive and life-threatening infection associated with a high risk of rapid multiorgan failure. It is associated with high morbidity and mortality. Streptococcal toxic shock syndrome is very commonly caused by group A-Streptococcus pyogenes, ß-haemolytic streptococcus, a typical human-specific gram-positive bacterial pathogen. We present here the case report of a 54-year-old man with a rapidly progressive streptococcal toxic shock syndrome due to necrotising fasciitis of the left lower limb and describe the successful treatment through close interdisciplinary care.

Free-Breathing and Single-Breath Hold Compressed Sensing Real-Time MRI of Right Ventricular Function in Children with Congenital Heart Disease.

(1) Purpose: to compare right ventricular (RV) functional parameters in children with surgically repaired congenital heart disease (CHD) using single/double breath hold (BH) and free-breathing (FB) real-time compressed sensing (CS) cine cardiac magnetic resonance (cMRI) with standard retrospective segmented multi breath hold (RMB) cine cMRI. (2) Methods: Twenty patients with CHD underwent BH and FB, as well as RMB cine cMRI, at 3T to obtain a stack of continuous axial images of the RV. Two radiologists independently performed qualitative analysis of the image quality (rated on a 5-point scale; 1 = non-diagnostic to 5 = excellent) and quantitative analysis of the RV volume measurements. (3) Results: The best image quality was provided by RMB (4.5; range 2-5) compared to BH (3.9; range 3-5; p = 0.04) and FB (3.6; range 3-5; p < 0.01). The RV functional parameters were comparable among BH, FB, and RMB with a difference of less than 5%. The scan times for BH (44 ± 38 s, p < 0.01) and FB (24 ± 7 s, p < 0.01) were significantly reduced compared to for RMB (261 ± 68 s). (4) Conclusions: CS-FB and CS-BH real-time cine cMRI in children with CHD provides diagnostic image quality with excellent accuracy for measuring RV function with a significantly reduced scan time compared to RMB.

Apparent Diffusion Coefficient (ADC) Histogram Analysis in Parotid Gland Tumors: Evaluating a Novel Approach for Differentiation between Benign and Malignant Parotid Lesions Based on Full Histogram Distributions.

The aim of this study was to assess the diagnostic value of ADC distribution curves for differentiation between benign and malignant parotid gland tumors and to compare with mean ADC values. 73 patients with parotid gland tumors underwent head-and-neck MRI on a 1.5 Tesla scanner prior to surgery and histograms of ADC values were extracted. Histopathological results served as a reference standard for further analysis. ADC histograms were evaluated by comparing their similarity to a reference distribution using Chi2-test-statistics. The assumed reference distribution for benign and malignant parotid gland lesions was calculated after pooling the entire ADC data. In addition, mean ADC values were determined. For both methods, we calculated and compared the sensitivity and specificity between benign and malignant parotid gland tumors and three subgroups (pleomorphic adenoma, Warthin tumor, and malignant lesions), respectively. Moreover, we performed cross-validation (CV) techniques to estimate the predictive performance between ADC distributions and mean values. Histopathological results revealed 30 pleomorphic adenomas, 22 Warthin tumors, and 21 malignant tumors. ADC histogram distribution yielded a better specificity for detection of benign parotid gland lesions (ADChistogram: 75.0% vs. ADCmean: 71.2%), but mean ADC values provided a higher sensitivity (ADCmean: 71.4% vs. ADChistogram: 61.9%). The discrepancies are most pronounced in the differentiation between malignant and Warthin tumors (sensitivity ADCmean: 76.2% vs. ADChistogram: 61.9%; specificity ADChistogram: 81.8% vs. ADCmean: 68.2%). Using CV techniques, ADC distribution revealed consistently better accuracy to differentiate benign from malignant lesions ("leave-one-out CV" accuracy ADChistogram: 71.2% vs. ADCmean: 67.1%). ADC histogram analysis using full distribution curves is a promising new approach for differentiation between primary benign and malignant parotid gland tumors, especially with respect to the advantage in predictive performance based on CV techniques.

Personalized Chest Computed Tomography: Minimum Diagnostic Radiation Dose Levels for the Detection of Fibrosis, Nodules, and Pneumonia.

OBJECTIVES: The purpose of this study was to evaluate the minimum diagnostic radiation dose level for the detection of high-resolution (HR) lung structures, pulmonary nodules (PNs), and infectious diseases (IDs). MATERIALS AND METHODS: A preclinical chest computed tomography (CT) trial was performed with a human cadaver without known lung disease with incremental radiation dose using tin filter-based spectral shaping protocols. A subset of protocols for full diagnostic evaluation of HR, PN, and ID structures was translated to clinical routine. Also, a minimum diagnostic radiation dose protocol was defined (MIN). These protocols were prospectively applied over 5 months in the clinical routine under consideration of the individual clinical indication. We compared radiation dose parameters, objective and subjective image quality (IQ). RESULTS: The HR protocol was performed in 38 patients (43%), PN in 21 patients (24%), ID in 20 patients (23%), and MIN in 9 patients (10%). Radiation dose differed significantly among HR, PN, and ID (5.4, 1.2, and 0.6 mGy, respectively; P < 0.001). Differences between ID and MIN (0.2 mGy) were not significant (P = 0.262). Dose-normalized contrast-to-noise ratio was comparable among all groups (P = 0.087). Overall IQ was perfect for the HR protocol (median, 5.0) and decreased for PN (4.5), ID-CT (4.3), and MIN-CT (2.5). The delineation of disease-specific findings was high in all dedicated protocols (HR, 5.0; PN, 5.0; ID, 4.5). The MIN protocol had borderline IQ for PN and ID lesions but was insufficient for HR structures. The dose reductions were 78% (PN), 89% (ID), and 97% (MIN) compared with the HR protocols. CONCLUSIONS: Personalized chest CT tailored to the clinical indications leads to substantial dose reduction without reducing interpretability. More than 50% of patients can benefit from such individual adaptation in a clinical routine setting. Personalized radiation dose adjustments with validated diagnostic IQ are especially preferable for evaluating ID and PN lesions.

Digitized and structured informed patient consent before contrast-enhanced computed tomography: feasibility and benefits in clinical routine.

BACKGROUND: To evaluate the feasibility and benefits of digitized informed patient consent (D-IPC) for contrast-enhanced CT and compare digitized documentation with paper-based, conventional patient records (C-PR). METHODS: We offered D-IPC to 2016 patients scheduled for a CT. We assessed patient history (e.g., CT examinations, malignant or cardiovascular diseases) and contraindications (red flags) for a CT (e.g., thyroid hyperfunction, allergies) using a tablet device. We evaluated the success rate of D-IPC and compared patient age between the subgroups of patients who were able or unable to complete D-IPC. We analyzed the prevalence of marked questions and red flags (RF). RF were compared with the documentation from C-PR. We estimated greenhouse gas (GHG) emissions for paperless workflow and provide a cost-benefit analysis. RESULTS: Overall, 84.4% of patients completed D-IPC. They were younger (median 61 years) than unsuccessful patients (65 years; p < 0.001). Patients who marked questions (21.7%) were older than patients without inquiries (median 63.9 vs 59.5 years; p < 0.001). The most prevalent RF was thyroid disease (23.8%). RF were considered critical for contrast-agent injection in 13.7%, requiring personalized preparation. The detection rate for RF documented with D-IPC was higher than for C-PR (n = 385 vs. 43). GHG emissions for tablet production are 80-90 times higher than for paper production. The estimated costs were slightly higher for D-IPC (+ 8.7%). CONCLUSION: D-IPC is feasible, but patient age is a relevant factor. Marked questions and RF help personalize IPC. The availability of patient history by D-IPC was superior compared to C-PR.

Case report of severe constrictive perimyocarditis and ischemic hepatitis in a Crohn's disease patient upon infliximab-induced lupus-like syndrome.

Anti-tumor necrosis factor (TNF) antibodies have become an indispensable part in the therapeutic landscape of treating inflammatory bowel disease (IBD) patients. Nevertheless, they can be associated with the occurrence of severe systemic side effects. Here, we report the case of a 23-year-old patient with ileocolonic Crohn's disease in endoscopic remission under ongoing anti-TNF infliximab therapy with occurrence of novel generalized arthralgia, pleuritic chest pain, and dyspnea. Clinical, laboratory, and imaging diagnostic workup in an extended clinical routine setting at the University Hospital of Erlangen, Germany, was used by a multidisciplinary team consisting of gastroenterologists, radiologists, cardiologists, and rheumatologists to investigate the underlying cause of the clinical symptoms in the patient. The results received using the aforementioned diagnostic setup led to the diagnosis of severe constrictive perimyocarditis due to infliximab-induced lupus-like syndrome with distinct ANA reactivity and elevated anti-dsDNA levels. Furthermore, pronounced ischemic hepatitis was diagnosed. Infliximab treatment was immediately stopped, and initiated corticosteroid pulse therapy only led to partial response as it had to be reduced due to pronounced psychiatric side effects. Persistent signs of pericarditis required additional ibuprofen therapy, which led to subsequent resolution of cardial symptoms. Formerly elevated liver enzymes returned to normal, and there were no clinical signs of recurrence of Crohn's disease activity over 18 months of follow-up. The patient was subsequently switched to ustekinumab therapy for further treatment of underlying Crohn's disease. This case report describes for the first time severe infliximab-induced lupus-like syndrome in an IBD patient, concurrently mimicking ST-elevation myocardial infarction with MRI visualization of pericarditis, occurrence of ischemic hepatitis, and pronounced signs of systemic inflammation.

68Ga-FAPI-04 PET-CT for molecular assessment of fibroblast activation and risk evaluation in systemic sclerosis-associated interstitial lung disease: a single-centre, pilot study.

BACKGROUND: Interstitial lung disease (ILD) is the most common cause of death in systemic sclerosis. To date, the progression of systemic sclerosis-associated ILD is judged by the accrual of lung damage on CT and pulmonary function tests. However, diagnostic tools to assess disease activity are not available. Here, we tested the hypothesis that quantification of fibroblast activation by PET-CT using a 68Ga-labelled selective inhibitor of prolyl endopeptidase FAP (68Ga-FAPI-04) would correlate with ILD activity and disease progression in patients with systemic sclerosis-associated ILD. METHODS: Between Sept 10, 2018, and April 8, 2020, 21 patients with systemic sclerosis-associated ILD confirmed by high-resolution CT (HRCT) within 12 months of inclusion and with onset of systemic sclerosis-associated ILD within 5 years or signs of progressive ILD and 21 controls without ILD were consecutively enrolled. All participants underwent 68Ga-FAPI-04 PET-CT imaging and standard-of-care procedures, including HRCT and pulmonary function tests at baseline. Patients with systemic sclerosis-associated ILD were followed for 6 months with HRCT and pulmonary function tests. We compared baseline 68Ga-FAPI-04 PET-CT uptake with standard diagnostic tools and predictors of ILD progression. The association of 68Ga-FAPI-04 uptake with changes in forced vital capacity was analysed using mixed-effects models. Follow-up 68Ga-FAPI-04 PET-CT scans were obtained in a subset of patients treated with nintedanib (follow-up between 6-10 months) to assess change over time. FINDINGS: 68Ga-FAPI-04 accumulated in fibrotic areas of the lungs in patients with systemic sclerosis-associated ILD compared with controls, with a median standardised uptake value (SUV) mean over the whole lung of 0·80 (IQR 0·60-2·10) in the systemic sclerosis-ILD group and 0·50 (0·40-0·50) in the control group (p<0·0001) and a mean whole lung maximal SUV of 4·40 (range 3·05-5·20) in the systemic sclerosis-ILD group compared with 0·70 (0·65-0·70) in the control group (p<0·0001). Whole-lung FAPI metabolic active volume (wlFAPI-MAV) and whole-lung total lesion FAPI (wlTL-FAPI) were not measurable in control participants, because no 68Ga-FAPI-04 uptake above background level was observed. In the systemic sclerosis-ILD group the median wlFAPI-MAV was 254·00 cm3 (IQR 163·40-442·30), and the median wlTL-FAPI was 183·60 cm3 (98·04-960·70). 68Ga-FAPI-04 uptake was higher in patients with extensive disease, with previous ILD progression, or high EUSTAR activity scores than in those with with limited disease, previously stable ILD, or low EUSTAR activity scores. Increased 68Ga-FAPI-04 uptake at baseline was associated with progression of ILD independently of extent of involvement on HRCT scan and the forced vital capacity at baseline. In consecutive 68Ga-FAPI-04 PET-CTs, changes in 68Ga-FAPI-04 uptake was concordant with the observed response to the fibroblast-targeting antifibrotic drug nintedanib. INTERPRETATION: Our study presents the first in-human evidence that fibroblast activation correlates with fibrotic activity and disease progression in the lungs of patients with systemic sclerosis-associated ILD and that 68Ga-FAPI-04 PET-CT might improve risk assessment of systemic sclerosis-associated ILD. FUNDING: German Research Foundation, Erlangen Anschubs-und Nachwuchsfinanzierung, Interdisziplinäres Zentrum für Klinische Forschung Erlangen, Bundesministerium für Bildung und Forschung, Deutsche Stiftung Systemische Sklerose, Wilhelm-Sander-Foundation, Else-Kröner-Fresenius-Foundation, European Research Council, Ernst-Jung-Foundation, and Clinician Scientist Program Erlangen.

Diagnostic value of 3D dynamic contrast-enhanced magnetic resonance imaging in lymph node metastases of head and neck tumors: a correlation study with histology.

BACKGROUND: Accurate staging of cervical lymph nodes (LN) is pivotal for further clinical management of patients with head and neck cancer. Functional magnetic resonance imaging (MRI) such as three-dimensional (3D) dynamic contrast-enhanced (DCE) acquisition might improve the diagnosis of cervical LN metastases. PURPOSE: To evaluate the additional diagnostic value of high-resolution 3D T1-weighted DCE in detecting LN metastasis compared to standard morphological imaging criteria in patients with head and neck tumors as correlated to histopathology. MATERIAL AND METHODS: Standard MRI with 3D DCE acquisition at voxel sizes of 1 × 1×1 mm was performed in 15 patients before surgery; 92 LN of the head and neck were histopathologically analyzed. A logistic regression analysis of semi-quantitative DCE parameters, time-intensity curve (TIC) shapes, and morphological criteria was performed to differentiate benign from malignant LN. RESULTS: Standard MRI was sufficient for diagnosis of malignancy in LN with a short-axis diameter ≥ 15 mm (n = 17). For LN metastases with a short-axis diameter <15 mm (n = 12), however, the combination of 3D DCE MRI parameters, TIC shapes, and LN diameter significantly increased the sensitivity and specificity of diagnosing metastases (DCE + TIC shape + LN diameter: 92% and 88% vs. DCE only: 83% and 68% (P < 0.01) vs. LN diameter only: 83% and 77% (P = 0.04). CONCLUSION: MRI including isotropic high-resolution 3D DCE acquisition combined with morphological criteria allows an accurate assessment of small cervical LN metastases in patients with head and neck cancer. For LN ≥ 15 mm diameter, morphologic imaging may suffice to diagnose metastatic disease to the LN.

Machine Learning Algorithms for Early Detection of Bone Metastases in an Experimental Rat Model.

Machine learning (ML) algorithms permit the integration of different features into a model to perform classification or regression tasks with an accuracy exceeding its constituents. This protocol describes the development of an ML algorithm to predict the growth of breast cancer bone macrometastases in a rat model before any abnormalities are observable with standard imaging methods. Such an algorithm can facilitate the detection of early metastatic disease (i.e., micrometastasis) that is regularly missed during staging examinations. The applied metastasis model is site-specific, meaning that the rats develop metastases exclusively in their right hind leg. The model's tumor-take rate is 60%-80%, with macrometastases becoming visible in magnetic resonance imaging (MRI) and positron emission tomography/computed tomography (PET/CT) in a subset of animals 30 days after induction, whereas a second subset of animals exhibit no tumor growth. Starting from image examinations acquired at an earlier time point, this protocol describes the extraction of features that indicate tissue vascularization detected by MRI, glucose metabolism by PET/CT, and the subsequent determination of the most relevant features for the prediction of macrometastatic disease. These features are then fed into a model-averaged neural network (avNNet) to classify the animals into one of two groups: one that will develop metastases and the other that will not develop any tumors. The protocol also describes the calculation of standard diagnostic parameters, such as overall accuracy, sensitivity, specificity, negative/positive predictive values, likelihood ratios, and the development of a receiver operating characteristic. An advantage of the proposed protocol is its flexibility, as it can be easily adapted to train a plethora of different ML algorithms with adjustable combinations of an unlimited number of features. Moreover, it can be used to analyze different problems in oncology, infection, and inflammation.

Cardiac T2 star mapping: standardized inline analysis of long and short axis at three identical 1.5 T MRI scanners.

T2 star mapping can be applied for in vivo cardiac iron quantification. Current recommendations of imaging acquisition, post-processing and interpretation of normal values are based on old scanner types and in house software packages. A standardized comparison of short (SAX) and long axis (LAX) segments using commercially available software packages and modern scanners is lacking. To provide a standardized comparison of T2 star time values in SAX and LAX and to investigate intersegmental, interregional and inter-level comparison and the interscanner reproducibility. 84 cardiac MRIs in 28 healthy volunteers were performed with three structurally identical 1.5 T MRI scanners. A commercially available software package for T2 star mapping with automatic in-line motion correction was used for analysis. Regions of interest were manually placed in each of the 16 myocardial segments according to the AHA model in three SAX and three LAX. A total of 2856 ROIs were drawn and 102 segments per volunteer were analysed. Interscanner reproducibility was high (91%) and the mean myocardial T2 star time value for all evaluated segments was 34 ± 5.7 ms. No significant difference was found between all measurements in SAX (35 ± 5.5 ms) and LAX (34 ± 5.8 ms). T2 star time values varied significantly between heart segments in the same axis and in 44% between corresponding SAX and LAX segments. T2 star time values in SAX and LAX have a high interscanner reproducibility but can vary significantly between heart segments in the same axis. Comparability between corresponding SAX and LAX segments is limited. To get representative results T2 star time values should be obtained in more than one heart segment and for follow-up studies identical segments should be used to avoid a systematic bias.

Complete Free-breathing Adenosine Stress Cardiac MRI Using Compressed Sensing and Motion Correction: Comparison of Functional Parameters, Perfusion, and Late Enhancement with the Standard Breath-holding Examination.

PURPOSE: To compare free-breathing (FB) stress cardiac MRI examinations with the reference standard breath-holding (BH) examination. MATERIALS AND METHODS: A total of 40 consecutive patients were enrolled prospectively and were examined with 3-T MRI. Functional imaging, perfusion, and late gadolinium enhancement (LGE) sequences were performed in BH and FB by using compressed sensing and in-line motion correction. Left ventricle (LV) and right ventricle (RV) functional parameters in BH and FB examinations were compared by using Bland-Altman plots and linear mixed models. Subjective image quality was assessed with a five-point scale (1 = nondiagnostic, 5 = very good). For perfusion and LGE imaging, diagnostic confidence was rated with a three-point scale (1 = low, 3 = high), and image quality was rated with a five-point scale (1 = nondiagnostic, 5 = very good). The Wilcoxon test was used to compare image quality and diagnostic confidence. RESULTS: Bland-Altman plots showed good agreement for LV and RV functional parameters in BH and FB sequences. Subjective image quality was significantly better with the BH sequences in the LV (P < .01) but was comparable in the RV (P > .99). Scanning time was 218 seconds (range, 130-385 seconds) for cine BH and 16 seconds (range, 11-27 seconds) for cine FB. Extent of perfusion defects, LGE, and diagnostic confidence was comparable between groups. Scanning time was 371 seconds (range, 239-502 seconds) for the LGE BH sequence and 189 seconds (range, 122-286 seconds) for the LGE FB sequence. CONCLUSION: FB adenosine stress cardiac MRI delivers diagnostic image quality and could represent an alternative for use in patients who are unable to meet the demands of multiple BHs and long examination times.© RSNA, 2019.