Assessment of blood-brain barrier leakage and brain oxygenation in Connexin-32 knockout mice with systemic neuroinflammation using pulse electron paramagnetic resonance imaging techniques.

PURPOSE: The determination of blood-brain barrier (BBB) integrity and partial pressure of oxygen (pO2) in the brain is of substantial interest in several neurological applications. This study aimed to assess the feasibility of using trityl OX071-based pulse electron paramagnetic resonance imaging (pEPRI) to provide a quantitative estimate of BBB integrity and pO2 maps in mouse brains as a function of neuroinflammatory disease progression. METHODS: Five Connexin-32 (Cx32)-knockout (KO) mice were injected with lipopolysaccharide to induce neuroinflammation for imaging. Three wild-type mice were also used to optimize the imaging procedure and as control animals. An additional seven Cx32-KO mice were used to establish the BBB leakage of trityl using the colorimetric assay. All pEPRI experiments were performed using a preclinical instrument, JIVA-25 (25 mT/720 MHz), at times t = 0, 4, and 6 h following lipopolysaccharide injection. Two pEPRI imaging techniques were used: (a) single-point imaging for obtaining spatial maps to outline the brain and calculate BBB leakage using the signal amplitude, and (b) inversion-recovery electron spin echo for obtaining pO2 maps. RESULTS: A statistically significant change in BBB leakage was found using pEPRI with the progression of inflammation in Cx32 KO animals. However, the change in pO2 values with the progression of inflammation for these animals was not statistically significant. CONCLUSIONS: For the first time, we show the ability of pEPRI to provide pO2 maps in mouse brains noninvasively, along with a quantitative assessment of BBB leakage. We expect this study to open new queries from the field to explore the pathology of many neurological diseases and provide a path to new treatments.

Long-axial field-of-view PET/CT for the assessment of inflammation in calcified coronary artery plaques with [68 Ga]Ga-DOTA-TOC.

PURPOSE: Inflamed, prone-to-rupture coronary plaques are an important cause of myocardial infarction and their early identification is crucial. Atherosclerotic plaques are characterized by overexpression of the type-2 somatostatin receptor (SST2) in activated macrophages. SST2 ligand imaging (e.g. with [68 Ga]Ga-DOTA-TOC) has shown promise in detecting and quantifying the inflammatory activity within atherosclerotic plaques. However, the sensitivity of standard axial field of view (SAFOV) PET scanners may be suboptimal for imaging coronary arteries. Long-axial field of view (LAFOV) PET/CT scanners may help overcome this limitation. We aim to assess the ability of [68 Ga]Ga-DOTA-TOC LAFOV-PET/CT in detecting calcified, SST2 overexpressing coronary artery plaques. METHODS: In this retrospective study, 108 oncological patients underwent [68 Ga]Ga-DOTA-TOC PET/CT on a LAFOV system. [68 Ga]Ga-DOTA-TOC uptake and calcifications in the coronary arteries were evaluated visually and semi-quantitatively. Data on patients' cardiac risk factors and coronary artery calcium score were also collected. Patients were followed up for 21.5 ± 3.4 months. RESULTS: A total of 66 patients (61.1%) presented with calcified coronary artery plaques. Of these, 32 patients had increased [68 Ga]Ga-DOTA-TOC uptake in at least one coronary vessel (TBR: 1.65 ± 0.53). Patients with single-vessel calcifications showed statistically significantly lower uptake (SUVmax 1.10 ± 0.28) compared to patients with two- (SUVmax 1.31 ± 0.29, p < 0.01) or three-vessel calcifications (SUVmax 1.24 ± 0.33, p < 0.01). There was a correlation between coronary artery calcium score (CACS) and [68 Ga]Ga-DOTA-TOC uptake, especially in the LAD (p = 0.02). Stroke and all-cause death occurred more frequently in patients with increased [68 Ga]Ga-DOTA-TOC uptake (15.63% vs. 0%; p:0.001 and 21.88% vs. 6.58%; p: 0.04, respectively) during the follow-up period. CONCLUSION: [68 Ga]Ga-DOTA-TOC as a marker for the macrophage activity can reveal unknown cases of inflamed calcified coronary artery plaques using a LAFOV PET system. [68 Ga]Ga-DOTA-TOC uptake increased with the degree of calcification and correlated with higher risk of stroke and all-cause death. [68 Ga]Ga-DOTA-TOC LAFOV PET/CT may be useful to assess patients' cardiovascular risk.

Coronary CT angiography for the assessment of atherosclerotic plaque inflammation: postmortem proof of concept with histological validation.

OBJECTIVES: To evaluate the diagnostic utility of multiphase postmortem CT angiography (PMCTA) to detect plaque enhancement as a surrogate marker of inflammation, using fatal coronary plaques obtained from autopsies following sudden cardiac death. METHODS: In this retrospective study, we included 35 cases (12 women, 34%; median [IQR] age, 52 [11] years), with autopsy-proven coronary thrombosis, histological examination, and multiphase PMCTA. Two radiologists blinded towards histological findings assessed PMCTA for plaque enhancement of the culprit lesion in consensus. Two forensic pathologists determined the culprit lesion and assessed histological samples in consensus. Cases with concomitant vasa vasorum density increase and intraplaque and periadventital inflammation were considered positive for plaque inflammation. Finally, we correlated radiology and pathology findings. RESULTS: All 35 cases had histological evidence of atherosclerotic plaque disruption and thrombosis; 30 (85.7%) had plaque inflammation. Plaque enhancement at multiphase PMCTA was reported in 21 (60%) and resulted in a PPV of 95.2% (77.3-99.2%) and an NPV of 28.6% (17-43.9%). Median histological ratings indicated higher intraplaque inflammation (p = .024) and vasa vasorum density (p = .032) in plaques with enhancement. We found no evidence of a difference in adventitial inflammation between CT-negative and CT-positive plaques (p = .211). CONCLUSIONS: Plaque enhancement was found in 2/3 of fatal atherothrombotic occlusions at coronary postmortem CT angiography. Furthermore, plaque enhancement correlated with histopathological plaque inflammation and increased vasa vasorum density. Plaque enhancement on multiphase CT angiography could potentially serve as a noninvasive marker of inflammation in high-risk populations. CLINICAL RELEVANCE STATEMENT: Phenotyping coronary plaque more comprehensively is one of the principal challenges cardiac imaging is facing. Translating our ex vivo findings of CT-based plaque inflammation assessment into clinical studies might help pave the way in defining high-risk plaque better. KEY POINTS: • Most thrombosed coronary plaques leading to fatality in our series had histological signs of inflammation. • Multiphase postmortem CT angiography can provide a noninvasive interrogation of plaque inflammation through contrast enhancement. • Atherosclerotic plaque enhancement at multiphase postmortem CT angiography correlated with histopathological signs of plaque inflammation and could potentially serve as an imaging biological marker of plaque vulnerability.

Crohn's disease inflammation severity assessment with iodine density from photon counting CT enterography: comparison with endoscopic histopathology.

PURPOSE: To determine optimal iodine density thresholds for active inflammation in CD patients with PCCT enterography and determine if iodine density can be used to stratify CD activity severity. METHODS: A retrospective PACS search identified patients with CD imaged with PCCT enterography from 4/11/2022 to 10/30/2022 and with clinical notes, endoscopic/surgical pathology and available source PCCT data for iodine density analysis. Two abdominal radiologists with expertise in CD each drew two region of interest measurements within the visibly most affected region of terminal or neoterminal ileum wall on commercially available system (SyngoVia). Radiologists were blinded to clinical information and pathologic findings. Disease activity and severity were recorded from the pathology report. Harvey-Bradshaw Index, medications, and laboratory values were recorded. Receiver operating characteristic (ROC) curves were utilized to determine the optimum iodine density threshold for active inflammation and mild versus moderate-to-severe inflammation. Intra- and inter-reader agreement was assessed by intra-class correlation coefficient (ICC). RESULTS: 23 CD patients (15 females; mean [SD] age: 52 [17] years) imaged with PCCT enterography were included. 15/23 had active inflammation: 9/15 mild, 4/15 moderate, and 2/15 severe active inflammation. The optimal iodine density threshold for active inflammation was 2.7 mg/mL, with 97% sensitivity, 100% specificity, and 98% accuracy (AUC = 1.00). The optimal iodine density threshold for distinguishing mild from moderate-to-severe inflammation was 3.4 mg/mL, with 83% sensitivity, 89% specificity, and 87% accuracy (AUC = 0.85). Intra-reader reliability (R1/R2) ICC was 0.81/0.86. Inter-reader reliability ICC was 0.94. CONCLUSION: Iodine density from PCCT enterography can distinguish mild from moderate-to-severe active inflammation.

Quantitative assessment of angioplasty-induced vascular inflammation with 19F cardiovascular magnetic resonance imaging.

BACKGROUND: Macrophages play a pivotal role in vascular inflammation and predict cardiovascular complications. Fluorine-19 magnetic resonance imaging (19F MRI) with intravenously applied perfluorocarbon allows a background-free direct quantification of macrophage abundance in experimental vascular disease models in mice. Recently, perfluorooctyl bromide-nanoemulsion (PFOB-NE) was applied to effectively image macrophage infiltration in a pig model of myocardial infarction using clinical MRI scanners. In the present proof-of-concept approach, we aimed to non-invasively image monocyte/macrophage infiltration in response to carotid artery angioplasty in pigs using 19F MRI to assess early inflammatory response to mechanical injury. METHODS: In eight minipigs, two different types of vascular injury were conducted: a mild injury employing balloon oversize angioplasty only (BA, n = 4) and a severe injury provoked by BA in combination with endothelial denudation (BA + ECDN, n = 4). PFOB-NE was administered intravenously three days after injury followed by 1H and 19F MRI to assess vascular inflammatory burden at day six. Vascular response to mechanical injury was validated using X-ray angiography, intravascular ultrasound and immunohistology in at least 10 segments per carotid artery. RESULTS: Angioplasty was successfully induced in all eight pigs. Response to injury was characterized by positive remodeling with predominantly adventitial wall thickening and concomitant infiltration of monocytes/macrophages. No severe adverse reactions were observed following PFOB-NE administration. In vivo 19F signals were only detected in the four pigs following BA + ECDN with a robust signal-to-noise ratio (SNR) of 14.7 ± 4.8. Ex vivo analysis revealed a linear correlation of 19F SNR to local monocyte/macrophage cell density. Minimum detection limit of infiltrated monocytes/macrophages was estimated at approximately 410 cells/mm2. CONCLUSIONS: In this proof-of-concept study, 19F MRI enabled quantification of monocyte/macrophage infiltration after vascular injury with sufficient sensitivity. This may provide the opportunity to non-invasively monitor vascular inflammation with MRI in patients after angioplasty or even in atherosclerotic plaques.

Contrast-enhanced ultrasound imaging for assessment of intestinal inflammation in rainbow trout.

The intestine is essential for nutritional uptake and as a barrier to pathogens. Inflammation of the intestine can result from chemical contaminants, dietary irritants, or disease and may lead to serious health consequences, including reduced growth rates or increased pathogen susceptibility. Traditionally, intestinal inflammation in fish has been detected through histology completed post-mortem through excision and processing of the affected tissue. However, in human clinical settings, tools have been developed to assess intestinal inflammation non-invasively. Contrast-enhanced ultrasound (CEUS) imaging is an important tool for measuring inflammation in patients because it is cost-effective and minimally invasive. Specifically, CEUS allows real-time visualization and quantification of vascular perfusion. Changes in blood flow are typical in areas of inflamed or diseased tissue, and by measuring these changes, it is possible to assess the degree of inflammation. We demonstrate that standard CEUS protocols used for small mammals can be used to quantify vascular perfusion in the intestines of rainbow trout. Our resolution was sufficient to measure a significant difference in perfusion between control and TNBS-inflamed trout intestines, with inflamed intestines showing decreased perfusion. The presence of inflammation in the TNBS-treated intestines was verified ex vivo histologically and was characterized by the thickening of intestinal folds. The minimally invasive nature of CEUS imaging presents the opportunity to evaluate intestinal health in novel ways by allowing for longitudinal observations and avoiding mortality in valuable or at-risk specimens. Recent developments of highly portable, cost-effective CEUS systems will allow broad application of this tool, from industry to research.

Longitudinal Assessment of Inflammatory Activity in Acute Type B Aortic Dissection with Integrated Fluorodeoxyglucose Positron Emission Tomography/Magnetic Resonance Imaging.

OBJECTIVE: The significance of the inflammatory response in the natural course of acute type B aortic dissection (ATBAD) is unknown. The aim was to characterise inflammation and its transformation over time in ATBAD using 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) with contrast enhanced magnetic resonance imaging (MRI). METHODS: Ten patients underwent FDG-PET/MRI within two weeks of ATBAD (acute phase), three to four months (subacute phase), nine to 12 months (early chronic phase), and 21 to 24 months (late chronic phase) after ATBAD. Target background ratios (TBRs) were measured in the ascending aorta, aortic arch, and descending aorta. MRI inflammatory markers were assessed in the descending aorta. RESULTS: Ten patients were included: median age 69 years, median clinical follow up 32 months. In the acute phase there was increased FDG uptake in the descending aorta (maximum TBR 5.8, SD [standard deviation] 1.3) compared with the ascending aorta (TBR 3.3, SD 0.8, p < .010) and arch (TBR 4.2, SD 0.6, p = .010). The maximum TBR of the descending aorta decreased from the acute to subacute phase (TBR 3.5, SD 0.6, p = .010) and further to the early chronic phase (TBR 2.9, SD 0.4, p = .030) but was stable thereafter. The acute phase maximum TBR in the ascending aorta (TBR 3.3) and arch (TBR 4.2) decreased to the subacute phase (ascending: TBR 2.8, SD 0.6, p = .020; arch: TBR 2.7, SD 0.4, p = .010) and was stable thereafter. Four patients underwent surgical aortic repair (three for aortic dilatation at one, five, and 28 months and one for visceral ischaemia at three weeks). MRI signs of inflammation were present in all surgically treated patients vs. two of six of medically treated patients (p= .048). CONCLUSION: ATBAD is associated with increased FDG uptake in the acute phase primarily in the descending aorta, but also involving the aortic arch and ascending aorta, indicating an inflammatory response in the whole aorta. Inflammation subsides early in the ascending aorta and arch (three months), whereas it stabilised later in the descending aorta (nine to 12 months). MRI signs of inflammation were more frequent in patients who later needed surgical treatment and merit further investigation.

Computed tomography and nuclear medicine for the assessment of coronary inflammation: clinical applications and perspectives.

There is increasing evidence that in patients with atherosclerotic cardiovascular disease (ASCVD) under optimal medical therapy, a persisting dysregulation of the lipid and glucose metabolism, associated with adipose tissue dysfunction and inflammation, predicts a substantial residual risk of disease progression and cardiovascular events. Despite the inflammatory nature of ASCVD, circulating biomarkers such as high-sensitivity C-reactive protein and interleukins may lack specificity for vascular inflammation. As known, dysfunctional epicardial adipose tissue (EAT) and pericoronary adipose tissue (PCAT) produce pro-inflammatory mediators and promote cellular tissue infiltration triggering further pro-inflammatory mechanisms. The consequent tissue modifications determine the attenuation of PCAT as assessed and measured by coronary computed tomography angiography (CCTA). Recently, relevant studies have demonstrated a correlation between EAT and PCAT and obstructive coronary artery disease, inflammatory plaque status and coronary flow reserve (CFR). In parallel, CFR is well recognized as a marker of coronary vasomotor function that incorporates the haemodynamic effects of epicardial, diffuse and small-vessel disease on myocardial tissue perfusion. An inverse relationship between EAT volume and coronary vascular function and the association of PCAT attenuation and impaired CFR have already been reported. Moreover, many studies demonstrated that 18F-FDG PET is able to detect PCAT inflammation in patients with coronary atherosclerosis. Importantly, the perivascular FAI (fat attenuation index) showed incremental value for the prediction of adverse clinical events beyond traditional risk factors and CCTA indices by providing a quantitative measure of coronary inflammation. As an indicator of increased cardiac mortality, it could guide early targeted primary prevention in a wide spectrum of patients. In this review, we summarize the current evidence regarding the clinical applications and perspectives of EAT and PCAT assessment performed by CCTA and the prognostic information derived by nuclear medicine.

Assessment of hepatic fibrosis and inflammation with look-locker T1 mapping and magnetic resonance elastography with histopathology as reference standard.

PURPOSE: To compare the diagnostic performance of T1 mapping and MR elastography (MRE) for staging of hepatic fibrosis and grading inflammation with histopathology as standard of reference. METHODS: 68 patients with various liver diseases undergoing liver biopsy for suspected fibrosis or with an established diagnosis of cirrhosis prospectively underwent look-locker inversion recovery T1 mapping and MRE. T1 relaxation time and liver stiffness (LS) were measured by two readers. Hepatic fibrosis and inflammation were histopathologically staged according to a standardized fibrosis (F0-F4) and inflammation (A0-A2) score. For statistical analysis, independent t test, and Mann-Whitney U test and ROC analysis were performed, the latter to determine the performance of T1 mapping and MRE for fibrosis staging and inflammation grading, as compared to histopathology. RESULTS: Histopathological analysis diagnosed 9 patients with F0 (13.2%), 21 with F1 (30.9%), 11 with F2 (16.2%), 10 with F3 (14.7%), and 17 with F4 (25.0%). Both T1 mapping and MRE showed significantly higher values for patients with significant fibrosis (F0-1 vs. F2-4; T1 mapping p < 0.0001, MRE p < 0.0001) as well as for patients with severe fibrosis or cirrhosis (F0-2 vs. F3-4; T1 mapping p < 0.0001, MRE p < 0.0001). T1 values and MRE LS were significantly higher in patients with inflammation (A0 vs. A1-2, both p = 0.01). T1 mapping showed a tendency toward lower diagnostic performance without statistical significance for significant fibrosis (F2-4) (AUC 0.79 vs. 0.91, p = 0.06) and with a significant difference compared to MRE for severe fibrosis (F3-4) (AUC 0.79 vs. 0.94, p = 0.03). For both T1 mapping and MRE, diagnostic performance for diagnosing hepatic inflammation (A1-2) was low (AUC 0.72 vs. 0.71, respectively). CONCLUSION: T1 mapping is able to diagnose hepatic fibrosis, however, with a tendency toward lower diagnostic performance compared to MRE and thus may be used as an alternative to MRE for diagnosing hepatic fibrosis, whenever MRE is not available or likely to fail due to intrinsic factors of the patient. Both T1 mapping and MRE are probably not sufficient as standalone methods to diagnose hepatic inflammation with relatively low diagnostic accuracy.

Crohn's disease active inflammation assessment with iodine density from dual-energy CT enterography: comparison with endoscopy and conventional interpretation.

PURPOSE: To compare terminal ileum (TI) mucosal iodine density obtained at dual-energy CT enterography (DECTE) with conventional CT interpretation and endoscopy in patients with Crohn's disease (CD). MATERIALS AND METHODS: Twenty-three CD patients (14 men; mean[SD] age:48.1[16.7] years) with endoscopy within 30 days of DECTE were retrospectively identified. An inflammatory bowel disease gastroenterologist reviewed endoscopic images. Two radiologists qualitatively assessed the presence of active TI inflammation. Mean iodine density normalized to the aorta (I%), mean absolute iodine density (I), and iodine density standard deviation (ISD) from the distal 2 cm ileum (TI) mucosa obtained using semiautomatic prototype software were compared with endoscopic assessment using Mann Whitney tests. The optimal threshold I% and I were determined from receiver operating curves (ROC). Sensitivity and specificity of conventional interpretation and determined iodine thresholds were compared using McNemar's test. Inter-reader agreement was assessed using kappa. A p < 0.05 indicated statistical significance. RESULTS: Twelve (52.1%) patients had endoscopic active inflammation. I% was 37.9[13.3]% for patients with and 21.7[7.5]% for patients without endoscopic active inflammation (p = 0.001). The optimal ROC threshold 24.6% had 100% sensitivity and 81.8% specificity (AUC = 0.909, 95% CI 0.777-1). I was 2.44[0.73]mg/mL for patients with and 1.77[1.00]mg/mL for patients without active endoscopic inflammation (p = 0.0455). The optimal ROC threshold 1.78 mg/mL I had 91.7% sensitivity and 63.6% specificity (AUC = 0.75, 95% CI 0.532-0.968). ISD was similar for patients with and without endoscopic active inflammation (0.82[0.33]mg/mL and 0.77[0.28]mg/mL, respectively, p = 0.37). Conventional interpretation sensitivity and specificity (R1/R2) were 83.3%/91.7% and 72.7%/54.5%, respectively (all p > 0.05) with moderate inter-reader agreement (Κ = 0.542[95% CI 0.0202-0.088]). CONCLUSION: Mean normalized iodine density is highly sensitive and specific for endoscopic active inflammation. DECTE could be considered as a surrogate to endoscopy in CD patients. Despite trends towards improved sensitivity and specificity compared with conventional interpretation, future larger studies are needed.

Bowel wall MRI T1 relaxation estimates for assessment of intestinal inflammation in pediatric Crohn's disease.

PURPOSE: To compare bowel wall T1 relaxation estimates in young patients with newly diagnosed ileal CD to healthy control participants, characterize their change over time in response to biologic medical therapy, and evaluate their associations with clinical markers of intestinal inflammation. MATERIALS AND METHODS: Patients with newly diagnosed ileal CD and healthy control participants were prospectively recruited between December 2018 and October 2021. Patients underwent research MRI examinations of the bowel at baseline and at 6-weeks and 6-months into biologic medical treatment; control participants underwent single MRI examinations. MRI examinations included native T1 relaxometry of the terminal ileum using a modified Look-Locker inversion recovery (MOLLI) sequence. T1 estimates were measured on scanner-generated parametric maps. Clinical markers of intestinal inflammation were recorded at each visit. Group differences were assessed using the Mann-Whitney U test; the Friedman test was used to assess longitudinal changes in T1 estimates. Spearman correlation was used to evaluate associations between T1 estimates and inflammatory markers. RESULTS: Nineteen participants with CD (12 males; median age 14 years) and 15 control participants (7 males; median age 17 years) were included in the study. Bowel wall T1 estimates in CD patients (median 1302 ms) were significantly longer compared to control participants (median 1159 ms) (p < 0.001). In CD patients, T1 estimates changed over time after treatment (p = 0.001), with largest reductions between baseline and 6-weeks (p < 0.001). T1 estimates correlated with inflammatory markers, including erythrocyte sedimentation rate (ρ = 0.35; p = 0.01), c-reactive protein level (ρ = 0.34; p = 0.02), and weighted Pediatric Crohn's Disease Activity Index (ρ = 0.39; p = 0.005). T1 estimates did not correlate with serum albumin (ρ = - 0.28; p = 0.051) and fecal calprotectin (ρ = 0.07; p = 0.63). CONCLUSION: Bowel wall T1 estimates are abnormally increased in newly diagnosed ileal CD patients and decrease in response to medical therapy.

Current situation and cost-effectiveness of 18F-FDG PET/CT for the diagnosis of fever of unknown origin and inflammation of unknown origin: A single-center, large-sample study from China.

PURPOSE: 18F-FDG PET/CT has an important role in the evaluation of fever of unknown origin (FUO) and inflammation of unknown origin (IUO). Our study was to investigate the current status of the inclusion of 18F-FDG PET/CT within FUO/ IUO diagnostic work-up and evaluate the cost-effectiveness of it in China. METHODS: A total of 741 FUO/IUO patients admitted to our hospital from January 2012 to December 2019 were retrospectively reviewed. The clinical characteristic, medical expenses to reach diagnosis and the proportion of definite etiological diagnosis achieved upon hospital discharge were compared between patients examined by 18F-FDG PET/CT (18F-FDG PET/CT group) and patients not examined by 18F-FDG PET/CT (non-18F-FDG PET/CT group). RESULTS: The mean age, proportion of critically-ill patients, proportion of rheumatologic diseases, the number of examinations and hospitalisation days to reach diagnosis in the 18F-FDG PET/CT group were significantly higher than those in the non-18F-FDG PET/CT group. The mean medical costs of 18F-FDG PET/CT group were significantly higher than those of non-18F-FDG PET/CT group, whereas the proportion of definite etiological diagnosis achieved upon hospital discharge of 18F-FDG PET/CT group was significantly higher than that of non-18F-FDG PET/CT group. The mean hospitalisation days and mean medical costs before diagnosis were significantly lower in patients who undertook 18F-FDG PET/CT ≤ 7 days after hospital admission than those in patients who undertook 18F-FDG PET/CT > 7 days after hospital admission. CONCLUSIONS: 18F-FDG PET/CT is mostly used in critically-ill and hard-to-diagnose FUO/IUO patients currently in China, which may conceal its cost-effective advantage. While the early use of 18F-FDG PET/CT according to patient characteristics and etiological clues could help to reduce hospitalization stay, limit medical costs, thus producing its diagnostic effect to the great extent.

The role of tender and swollen joints for the assessment of inflammation in PsA using ultrasound.

OBJECTIVE: To evaluate tender joints (TJ) and swollen joints (SJ) for the assessment of ultrasound (US) defined inflammation in PsA. METHODS: Eighty-three PsA patients underwent clinical and US examinations at two scheduled study visits 12 months apart. Tenderness and swelling were assessed at 68 and 66 joints, respectively, and US examinations were conducted at all 68 joints. At patient level, associations with clinical composites and US scores were performed using correlations and by analysing patients with predominantly tender (pTender) or swollen joints (pSwollen). At joint level, a Power Doppler (PD) value ≥ 1 was defined as active synovitis. A generalized linear mixed model was created to assess the predictive value of TJ and SJ for active synovitis after 12 months. RESULTS: SJC showed better correlations with GS/PD scores (r = 0.37/0.47) than with TJC (PD: r = 0.33), while TJC correlated better with patient reported outcomes (PROMs) like patient global assessment (TJC: r = 0.57; SJC r = 0.39). Patients with pTender showed poorer results for PROMs and disease activity scores than patients with pSwollen, but not for laboratory or US markers of inflammation. Swollen joints showed active synovitis in 35% of cases, while only 16% of tender joints were active according to US. Swelling at baseline better predicted active synovitis at the same joint after 12 months [odds ratio (OR) 6.33, P <0.001] as compared with tenderness (OR 3.58, P <0.001). CONCLUSIONS: SJ are more closely linked with US signs of inflammation as compared with TJ in PsA. Joint swelling is a better predictor for signs of US inflammation than tenderness after one year of follow-up.

Multi-shot Diffusion-Weighted MRI With Multiplexed Sensitivity Encoding (MUSE) in the Assessment of Active Inflammation in Crohn's Disease.

BACKGROUND: Single-shot diffusion-weighted imaging (ssDWI) has been shown useful for detecting active bowel inflammation in Crohn's disease (CD) without MRI contrast. However, ssDWI suffers from geometric distortion and low spatial resolution. PURPOSE: To compare conventional ssDWI with higher-resolution ssDWI (HR-ssDWI) and multi-shot DWI based on multiplexed sensitivity encoding (MUSE-DWI) for evaluating bowel inflammation in CD, using contrast-enhanced MR imaging (CE-MRI) as the reference standard. STUDY TYPE: Prospective. SUBJECTS: Eighty nine patients with histological diagnosis of CD from previous endoscopy (55 male/34 female, age: 17-69 years). FIELD STRENGTH/SEQUENCES: ssDWI (2.7 mm × 2.7 mm), HR-ssDWI (1.8 mm × 1.8 mm), MUSE-DWI (1.8 mm × 1.8 mm) based on echo-planar imaging, T2-weighted imaging, and CE-MRI sequences, all at 1.5 T. ASSESSMENT: Five raters independently evaluated the tissue texture conspicuity, geometry accuracy, minimization of artifacts, diagnostic confidence, and overall image quality using 5-point Likert scales. The diagnostic performance (sensitivity, specificity and accuracy) of each DWI sequences was assessed on per-bowel-segment basis. STATISTICAL TESTS: Inter-rater agreement for qualitative evaluation of each parameter was measured by the intra-class correlation coefficient (ICC). Paired Wilcoxon signed-rank tests were performed to evaluate the statistical significance of differences in qualitative scoring between DWI sequences. A P value <0.05 was considered to be statistically significant. RESULTS: Tissue texture conspicuity, geometric distortions, and overall image quality were significantly better for MUSE-DWI than for ssDWI and HR-ssDWI with good agreement among five raters (ICC: 0.70-0.89). HR-ssDWI showed significantly poorer performance to ssDWI and MUSE-DWI for all qualitative scores and had the worst diagnostic performance (sensitivity of 57.0% and accuracy of 87.3%, with 36 undiagnosable cases due to severe artifacts). MUSE-DWI showed significantly higher sensitivity (97.5% vs. 86.1%) and accuracy (98.9% vs. 95.1%) than ssDWI for detecting bowel inflammation. DATA CONCLUSION: MUSE-DWI was advantageous in assessing bowel inflammation in CD, resulting in improved spatial resolution and image quality. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 2.

Preliminary Assessment of the Anti-inflammatory Activity of New Structural Honokiol Analogs with a 4'-O-(2-Fluoroethyl) Moiety and the Potential of Their 18F-Labeled Derivatives for Neuroinflammation Imaging.

Neolignans honokiol and 4'-O-methylhonokiol (MH) and their derivatives have pronounced anti-inflammatory activity, as evidenced by numerous pharmacological studies. Literature data suggested that cyclooxygenase type 2 (COX-2) may be a target for these compounds in vitro and in vivo. Recent studies of [11C]MPbP (4'-[11C]methoxy-5-propyl-1,1'-biphenyl-2-ol) biodistribution in LPS (lipopolysaccharide)-treated rats have confirmed the high potential of MH derivatives for imaging neuroinflammation. Here, we report the synthesis of four structural analogs of honokiol, of which 4'-(2-fluoroethoxy)-2-hydroxy-5-propyl-1, 1'-biphenyl (F-IV) was selected for labeling with fluorine-18 (T1/2 = 109.8 min) due to its high anti-inflammatory activity confirmed by enzyme immunoassays (EIA) and neuromorphological studies. The high inhibitory potency of F-IV to COX-2 and its moderate lipophilicity and chemical stability are favorable factors for the preliminary evaluation of the radioligand [18F]F-IV in a rodent model of neuroinflammation. [18F]F-IV was prepared with good radiochemical yield and high molar activity and radiochemical purity by 18F-fluoroethylation of the precursor with Boc-protecting group (15) with [18F]2-fluoro-1-bromoethane ([18F]FEB). Ex vivo biodistribution studies revealed a small to moderate increase in radioligand uptake in the brain and peripheral organs of LPS-induced rats compared to control animals. Pretreatment with celecoxib resulted in significant blocking of radioactivity uptake in the brain (pons and medulla), heart, lungs, and kidneys, indicating that [18F]F-IV is likely to specifically bind to COX-2 in a rat model of neuroinflammation. However, in comparison with [11C]MPbP, the new radioligand showed decreased brain uptake in LPS rats and high retention in the blood pool, which apparently could be explained by its high plasma protein binding. We believe that the structure of [18F]F-IV can be optimized by replacing the substituents in the biphenyl core to eliminate these disadvantages and develop new radioligands for imaging activated microglia.

Crohn Disease Active Inflammation Assessment with Iodine Density from Dual-Energy CT Enterography: Comparison with Histopathologic Analysis.

Background Dual-energy CT enterography (DECTE) has been shown to be useful in characterizing Crohn disease activity compared with clinical markers of inflammation but, to the knowledge of the authors, comparison has not been made with histopathologic specimens. Purpose To compare mucosal iodine density obtained at DECTE from Crohn disease-affected bowel with histopathologic specimens from surgically resected ileocolectomy bowel segments or terminal ileum colonoscopic biopsies in the same patients. Materials and Methods This was a retrospective study. Bowel segments in adults with Crohn disease who underwent DECTE from January 2017 to April 2019 within 90 days of ileocolectomy or colonoscopy were retrospectively evaluated with prototype software allowing the semiautomatic determination of inner hyperdense bowel wall (mucosal) mean iodine density, normalized to the aorta. Mean normalized iodine density and clinical activity indexes (Crohn Disease Activity Index [CDAI] and Harvey-Bradshaw Index [HBI]) were compared with histologic active inflammation grades by using two-tailed t tests. Receiver operating characteristic curves were generated for mean normalized iodine density, CDAI, and HBI to determine sensitivity, specificity, and accuracy. A P value less than .05 was considered to indicate statistical significance. Results The following 16 patients were evaluated (mean age, 41 years ± 14 [standard deviation]): 10 patients (five men, five women; mean age, 41 years ± 15) with 19 surgical resection specimens and six patients with terminal ileum colonoscopic mucosal biopsies (four men, two women; mean age, 43 years ± 14). Mean normalized iodine density was 16.5% ± 5.7 for bowel segments with no active inflammation (n = 8) and 34.7% ± 9.7 for segments with any active inflammation (n = 17; P < .001). A 20% mean normalized iodine density threshold had sensitivity, specificity, and accuracy of 17 of 17 (100%; 95% CI: 80.5, 100), six of eight (75%; 95% CI: 35, 97), and 23 of 25 (92%; 95% CI: 74, 99), respectively, for active inflammation. Clinical indexes were similar for patients with and without active inflammation at histopathologic analysis (CDAI score, 261 vs 251, respectively [P = .77]; HBI score, 7.8 vs 6.4, respectively [P = .36]). Conclusion Iodine density from dual-energy CT enterography may be used as a radiologic marker of Crohn disease activity as correlated with histopathologic analysis. © RSNA, 2021 See also the editorial by Ohliger in this issue.

The feasibility of T2 mapping in the assessment of hepatic steatosis, inflammation, and fibrosis in patients with non-alcoholic fatty liver disease: a preliminary study.

AIM: To determine the feasibility of magnetic resonance imaging T2 mapping in the quantification of liver steatosis in patients with biopsy-proven non-alcoholic fatty liver disease (NAFLD), and to assess the effect of inflammation and fibrosis on T2 values of the liver. MATERIAL AND METHODS: Twenty-three consecutive patients with biopsy-proven NAFLD who underwent T2 mapping between December 2013 and September 2014 were included in this study. All patients underwent fast spin echo multi-echo sequence with eight echoes for T2 measurements. RESULTS: The mean liver T2 value and percentage of histological steatosis was 64.9 ± 7.4 ms and 46.5 ± 27.6%, respectively. There was a good correlation between the liver T2 value and histology-determined steatosis (r = 0.780, p<0.001) and grade of steatosis (rs = 0.779, p<0.001). The mean T2 value in patients with definitive non-alcoholic steatohepatitis (NASH) was significantly higher in comparison with patients without NASH (69 ± 7.37 versus 61.73 ± 5.99 ms, p=0.016). The correlation between T2 value and NAFLD activity score (NAS) was significant (rs = 0.443, p=0.034); however, the correlation disappeared after adjustment for hepatic steatosis and fibrosis (r=0.131, p=0.572). There was a close inverse correlation between T2 value and fibrosis stage after adjusting for hepatic steatosis (r=-0.536, p=0.012). CONCLUSION: T2 mapping can be used for quantification of hepatic steatosis, as there is a close correlation between T2 relaxation values and histology-determined steatosis. Patients with definite NASH have increased T2 values and there is an inverse correlation between the T2 value and fibrosis stage of the liver. T2 mapping in NAFLD may be a useful clinical tool for disease assessment and prognostication.