Dual-energy CT in acute cholecystitis- features predicting culture-positive bile and outcome.

PURPOSE: Low mono-energetic CT has been shown to improve visualization of acute abdominal inflammatory processes. We aimed to determine its utility in patients with acute cholecystitis and potential added value in clinical decision making. METHODS: Sixty-seven consecutive patients with radiological signs of cholecystitis on contrast-enhanced dual-layer CT imaging were retrospectively identified over a four-year period (2/17-8/21). A ranked Likert scale was created for imaging findings present in acute cholecystitis, including gallbladder mucosal integrity and enhancement and pericholecystic liver parenchymal enhancement. These rankings were correlated with laboratory data, followed by sensitivity, specificity, and odds-ratios calculations. RESULTS: Mucosal integrity and pericholecystic liver enhancement were better seen on low-energetic images by unanimous consensus. Presence of pericholecystic liver enhancement and poorer mucosal wall integrity correlated with positive bile cultures (sensitivity: 93.8 % and 96.9 %, specificity: 37.5 and 50.0 %; odds-ratio: 9.0[1.1-68.1 95 %CI] and 31.0 [2.7-350.7 95 %CI], p = 0.017 and p ≤ 0.001) in patients undergoing cholecystostomy (n = 40/67). Moreover, binary regression modeling showed that the strongest predictor variable for bile culture positivity was the score for pericholecystic liver enhancement (Exp(B) = 0.6, P = 0.022). By contrast, other laboratory markers and other imaging findings (such as GB wall thickness) showed lower sensitivities (76-82 %), specificities (16-21 %) and odds ratios (0.2-4.4) for the prediction of infected bile. CONCLUSIONS: Pericholecystic liver enhancement and gallbladder wall integrity are better visualized on low-DECT images. These findings also potentially predict bile culture positivity in patients with cholecystitis, which may influence clinical management including the need for intervention.

Evaluation of the Pulmonary Arteries on CTPA With Dual Energy CT: Objective Analysis and Subjective Preferences in a Multireader Study.

PURPOSE: To perform qualitative and quantitative evaluation of low-monoenergetic images (50 KeV) compared with conventional images (120 kVp) in pulmonary embolism (PE) studies and to determine the extent and clinical relevance of these differences as well as radiologists' preferences. MATERIALS AND METHODS: One hundred fifty CT examinations for PE detection conducted on a single-source dual-energy CT were retrospectively evaluated. Attenuation, contrast-to-noise-ratio, and signal-to-noise-ratio were obtained in a total of 8 individual pulmonary arteries on each exam-including both central (450/1200=37.5%) and peripheral (750/1200=62.5%) locations. Results were compared between the conventional and low-monoenergetic images. For quality assessment, 41 images containing PE were presented side-by-side as pairs of slices in both conventional and monoenergetic modes and evaluated for ease in embolus detection by 9 radiologists: cardiothoracic specialists (3), noncardiothoracic specialists (3), and residents (3). Paired samples t tests, a-parametric Wilcoxon test, McNemar test, and kappa statistics were performed. RESULTS: Monoenergetic images had an overall statistically significant increased average ratio of 2.09 to 2.26 (P<0.05) for each measured vessel attenuation, with an increase in signal-to-noise ratio (23.82±9.29 vs. 11.39±3.2) and contrast-to-noise ratio (17.17±6.7 vs 7.27±2.52) (P<0.05). Moreover, 10/150 (6%) of central pulmonary artery measurements considered suboptimal on conventional mode were considered diagnostic on the monoenergetic images (181±14.6 vs. 387.7±72.4 HU respectively, P<0.05). In the subjective evaluation, noncardiothoracic radiologists showed a preference towards low-monoenergetic images, whereas cardiothoracic radiologists did not (74.4% vs. 57.7%, respectively, P<0.05). CONCLUSIONS: The SNR and CNR increase on monoenergetic images may have clinical significance particularly in the setting of sub-optimal PE studies. Noncardiothoracic radiologists and residents prefer low monoenergetic images.

MC3DU-Net: a multisequence cascaded pipeline for the detection and segmentation of pancreatic cysts in MRI.

PURPOSE: Radiological detection and follow-up of pancreatic cysts in multisequence MRI studies are required to assess the likelihood of their malignancy and to determine their treatment. The evaluation requires expertise and has not been automated. This paper presents MC3DU-Net, a novel multisequence cascaded pipeline for the detection and segmentation of pancreatic cysts in MRI studies consisting of coronal MRCP and axial TSE MRI sequences. METHODS: MC3DU-Net leverages the information in both sequences by computing a pancreas Region of Interest (ROI) segmentation in the TSE MRI scan, transferring it to MRCP scan, and then detecting and segmenting the cysts in the ROI of the MRCP scan. Both the voxel-level ROI of the pancreas and the segmentation of the cysts are performed with 3D U-Nets trained with Hard Negative Patch Mining, a new technique for class imbalance correction and for the reduction in false positives. RESULTS: MC3DU-Net was evaluated on a dataset of 158 MRI patient studies with a training/validation/testing split of 118/17/23. Ground truth segmentations of a total of 840 cysts were manually obtained by expert clinicians. MC3DU-Net achieves a mean recall of 0.80 ± 0.19, a mean precision of 0.75 ± 0.26, a mean Dice score of 0.80 ± 0.19 and a mean ASSD of 0.60 ± 0.53 for pancreatic cysts of diameter > 5 mm, which is the clinically relevant endpoint. CONCLUSION: MC3DU-Net is the first fully automatic method for detection and segmentation of pancreatic cysts in MRI. Automatic detection and segmentation of pancreatic cysts in MRI can be performed accurately and reliably. It may provide a method for precise disease evaluation and may serve as a second expert reader.

Optimal CT windowing on low-monoenergetic images using a simplex algorithm-based approach for abdominal inflammatory processes.

BACKGROUND: OBJECTIVES: To determine optimal window settings for conspicuity of abdominal inflammatory processes on 50 keV low-monoenergetic images derived from dual-energy spectral CT (DECT). METHODS: A retrospective study of 30 patients with clinically proven pancreatitis (15/30) or pyelonephritis (15/30) with inflammatory lesions visible on DECT scans were selected to serve as reference populations. 50 keV low-monoenergetic images in the portal venous phase were iteratively evaluated by 6 abdominal radiologists in twenty-one different windows (7-350HU center; 120-580HU width), selected using a simplex optimization algorithm. Each reader graded the conspicuity of the parenchymal hypodense lesions and image background quality. Three-dimensional contour maps expressing the relationship between overall reader grade and window center and width were constructed and used to find the ideal window for inflammatory pancreatic and renal processes and the image background quality. Finally, 15 appendicitis cases were reviewed on optimal pancreas and kidney windows and the manufacturer recommended conventional abdominal window settings for conventional imaging. RESULTS: Convergence to optimal windowing was achieved based upon a total of 3,780 reads (21 window settings × 6 readers × 15 cases for pancreas and kidney). Highest conspicuity grade (>4.5 ± 0.0) for pancreas inflammatory lesions was seen at 116HU/430HU, whereas hypodense pyelonephritis had highest conspicuity at 290HU/570HU. This rendered an ideal "compromise" window (>4 ± 0.2) of 150HU/450HU which differed substantially from conventional manufacturer recommended settings of 50HU/380HU (2.1 ± 1.0, p = 0.00001). Appendix mucosal enhancement was best visualized at manufacturer settings. CONCLUSIONS: Optimal visualization of inflammatory processes in abdominal organs on 50 keV low-monoenergetic images may require tailored refinement of window settings.

Real-time influence of intracellular acidification and Na+ /H+ exchanger inhibition on in-cell pyruvate metabolism in the perfused mouse heart: A 31 P-NMR and hyperpolarized 13 C-NMR study.

Disruption of acid-base balance is linked to various diseases and conditions. In the heart, intracellular acidification is associated with heart failure, maladaptive cardiac hypertrophy, and myocardial ischemia. Previously, we have reported that the ratio of the in-cell lactate dehydrogenase (LDH) to pyruvate dehydrogenase (PDH) activities is correlated with cardiac pH. To further characterize the basis for this correlation, these in-cell activities were investigated under induced intracellular acidification without and with Na+ /H+ exchanger (NHE1) inhibition by zoniporide. Male mouse hearts (n = 30) were isolated and perfused retrogradely. Intracellular acidification was performed in two ways: (1) with the NH4 Cl prepulse methodology; and (2) by combining the NH4 Cl prepulse with zoniporide. 31 P NMR spectroscopy was used to determine the intracellular cardiac pH and to quantify the adenosine triphosphate and phosphocreatine content. Hyperpolarized [1-13 C]pyruvate was obtained using dissolution dynamic nuclear polarization. 13 C NMR spectroscopy was used to monitor hyperpolarized [1-13 C]pyruvate metabolism and determine enzyme activities in real time at a temporal resolution of a few seconds using the product-selective saturating excitation approach. The intracellular acidification induced by the NH4 Cl prepulse led to reduced LDH and PDH activities (-16% and -39%, respectively). This finding is in line with previous evidence of reduced myocardial contraction and therefore reduced metabolic activity upon intracellular acidification. Concomitantly, the LDH/PDH activity ratio increased with the reduction in pH, as previously reported. Combining the NH4 Cl prepulse with zoniporide led to a greater reduction in LDH activity (-29%) and to increased PDH activity (+40%). These changes resulted in a surprising decrease in the LDH/PDH ratio, as opposed to previous predictions. Zoniporide alone (without intracellular acidification) did not change these enzyme activities. A possible explanation for the enzymatic changes observed during the combination of the NH4 Cl prepulse and NHE1 inhibition may be related to mitochondrial NHE1 inhibition, which likely negates the mitochondrial matrix acidification. This effect, combined with the increased acidity in the cytosol, would result in an enhanced H+ gradient across the mitochondrial membrane and a temporarily higher pyruvate transport into the mitochondria, thereby increasing the PDH activity at the expense of the cytosolic LDH activity. These findings demonstrate the complexity of in-cell cardiac metabolism and its dependence on intracellular acidification. This study demonstrates the capabilities and limitations of hyperpolarized [1-13 C]pyruvate in the characterization of intracellular acidification as regards cardiac pathologies.

Effect of Magnetic Resonance Imaging on Acute Surgical Treatment of Pregnant Patients: A Single Institution Study.

BACKGROUND: Abdominal pathology in pregnant patients is a frequent challenge for emergency department physicians. Ultrasound is the imaging modality of choice but is inconclusive in approximately one-third of cases. Magnetic resonance imaging (MRI) is becoming increasingly available, even in acute settings. Multiple studies have defined the sensitivity and specificity of MRI in this population. OBJECTIVES: To evaluate the use of MRI findings in pregnant patients presenting with acute abdominal complaints to the emergency department. METHODS: This retrospective cohort study was conducted at a single institution. Data were collected on pregnant patients who underwent an MRI for acute abdominal complaints between 2010 and 2019 at a university center. Patient demographics, diagnosis at admission, ultrasound and MRI findings, and discharge diagnosis were recorded and evaluated. RESULTS: In total, 203 pregnant patients underwent an MRI for acute abdominal complaints during the study period. MRI was found without pathology in 138 cases (68%). In 65 cases (32%), the MRI showed findings that could explain the patient's clinical presentation. Patients presenting with long-standing abdominal pain (> 24 hours), fever, leukocytosis, or elevated C-reactive protein values were at a significantly increased risk of having an acute pathology. In 46 patients (22.6%), MRI findings changed the primary diagnosis and management while in 45 patients (22.1%) MRI findings improved characterization of the suspected pathology. CONCLUSIONS: MRI is helpful when clinical and sonographic findings are inconclusive, leading to changes in patient management in more than one-fifth of patients.

Investigating Cardiac Metabolism in the Isolated Perfused Mouse Heart with Hyperpolarized [1-13C]Pyruvate and 13C/31P NMR Spectroscopy.

Metabolism is the basis of important processes in cellular life. Characterizing how metabolic networks function in living tissues provides crucial information for understanding the mechanism of diseases and designing treatments. In this work, we describe procedures and methodologies for studying in-cell metabolic activity in a retrogradely perfused mouse heart in real-time. The heart was isolated in situ, in conjunction with cardiac arrest to minimize the myocardial ischemia and was perfused inside a nuclear magnetic resonance (NMR) spectrometer. While in the spectrometer and under continuous perfusion, hyperpolarized [1-13C]pyruvate was administered to the heart, and the subsequent hyperpolarized [1-13C]lactate and [13C]bicarbonate production rates served to determine, in real-time, the rates of lactate dehydrogenase and pyruvate dehydrogenase production. This metabolic activity of hyperpolarized [1-13C]pyruvate was quantified with NMR spectroscopy in a model free-manner using the product selective saturating-excitations acquisition approach. 31P spectroscopy was applied in between the hyperpolarized acquisitions to monitor the cardiac energetics and pH. This system is uniquely useful for studying metabolic activity in the healthy and diseased mouse heart.

Focal Irreversible Electroporation for Localized Prostate Cancer - Oncological and Safety Outcomes Using mpMRI and Transperineal Biopsy Follow-Up.

Introduction: Irreversible electroporation (IRE) technology for prostate cancer (PC) generates consecutive electrical pulses between pairs of electrodes which move through tumorous cells, irreversibly perforate their membranes and eventually lead to cell death, while avoiding tissue thermal effect. The technique is used for primary focal lesions as well as for focal salvage cases. This series reports short term oncological control, quality of life and safety results. Methods: Retrospective data were collected from 45 consecutive cases of primary (N=38) and salvage (N=7) PC patients treated with IRE. All patients had transperineal MRI/US fusion biopsy and PET-PSMA scan prior to treatment, to verify single lesion. Transperineal Nano-Knife IRE system was used in day-care theatre. Patients had 6 months mpMRI, blood PSA and 1 year confirmatory biopsy following procedure. Quality of life was recorded during the first year. Results: Median primary subgroup analysis (N=38): age 69 years, initial PSA 5.6 ng/dL, lesion size 0.8 mL and ISUP Group 2 (1-3). Median salvage subgroup analysis (N=7): age 76 years, initial PSA 11.9 ng/dL, lesion size 2.0 mL and ISUP Group 4 (1-5). Median catheter time 5 (3-7) days. No Clavien-Dindo>1 complications were reported nor re-admissions, incontinence, strictures or fistulas. 5% of patients were given PDE-5i drugs. Primary group PSA dropped by 39%, mpMRI clearance in 84%, out-field new lesion in 12%, in-field lesion in 4%. Biopsy at 1 year: 4 patients had out-field clinically significant PC, thus 3 had re-IRE and 1 had radiation therapy. Salvage subgroup MRI clearance was 60%, and 52% remained on active surveillance by 1 year. Conclusion: IRE treatment for focal PC is safe for primary and salvage cases, if done by a meticulously skilled and trained team, and under strict protocols. The short term oncological results are promising especially for primary lesions. Long term oncological results will be published over time.

Existing Scores Fail to Predict Bowel Ischemia in Patients With Adhesive Small Bowel Obstruction.

INTRODUCTION: Early recognition of bowel ischemia is critical in patients suffering from acute adhesive small bowel obstruction (ASBO). Recent studies attempted to propose a score combining clinical and radiological factors to predict the risk of bowel ischemia in patients with ASBO. This study aimed to compare and validate the existing clinical scores with a cohort of surgical patients. METHODS: We conducted a retrospective study including all ASBO cases admitted to our institution between January 1, 2005 and December 31, 2019. Based on three existing clinical scores, we calculated the risk of bowel ischemia for each patient. We then divided the cohort into groups based on the risk for bowel ischemia. For each risk-based category, the proportion of patients who underwent surgical resection and were found to have evidence of ischemic bowel was calculated. RESULTS: A total of 160 patients presenting with 217 episodes of acute ASBO were included. One hundred seventy-one (78.8%) cases were managed nonoperatively while 46 cases (21.2%) required surgery. Sixteen patients (7.3%) were eventually found to have ischemic bowel while 13 required small bowel resection (5.9%). All three clinical scores showed correlation between the calculated risk of ischemia and the intraoperative finding of ischemia. However, all three scores overestimated ischemia rates in the high-risk groups, yielding a PPV of 8.3%-28.5% and a NPV of 93.3%-94.7%. CONCLUSIONS: Current clinical scores for predicting bowel ischemia in patients with ASBO are of high value in ruling out ischemia, yet are of extremely low sensitivity, warranting an overly aggressive and unnecessary surgical approach.

The Liver Tumor Segmentation Benchmark (LiTS).

In this work, we report the set-up and results of the Liver Tumor Segmentation Benchmark (LiTS), which was organized in conjunction with the IEEE International Symposium on Biomedical Imaging (ISBI) 2017 and the International Conferences on Medical Image Computing and Computer-Assisted Intervention (MICCAI) 2017 and 2018. The image dataset is diverse and contains primary and secondary tumors with varied sizes and appearances with various lesion-to-background levels (hyper-/hypo-dense), created in collaboration with seven hospitals and research institutions. Seventy-five submitted liver and liver tumor segmentation algorithms were trained on a set of 131 computed tomography (CT) volumes and were tested on 70 unseen test images acquired from different patients. We found that not a single algorithm performed best for both liver and liver tumors in the three events. The best liver segmentation algorithm achieved a Dice score of 0.963, whereas, for tumor segmentation, the best algorithms achieved Dices scores of 0.674 (ISBI 2017), 0.702 (MICCAI 2017), and 0.739 (MICCAI 2018). Retrospectively, we performed additional analysis on liver tumor detection and revealed that not all top-performing segmentation algorithms worked well for tumor detection. The best liver tumor detection method achieved a lesion-wise recall of 0.458 (ISBI 2017), 0.515 (MICCAI 2017), and 0.554 (MICCAI 2018), indicating the need for further research. LiTS remains an active benchmark and resource for research, e.g., contributing the liver-related segmentation tasks in http://medicaldecathlon.com/. In addition, both data and online evaluation are accessible via https://competitions.codalab.org/competitions/17094.

The effect of atrophied pancreas as shown in the preoperative imaging on the leakage rate after pancreaticoduodenectomy.

Backgrounds/Aims: The soft texture of the pancreas parenchyma may influence the incidence of pancreatic leakage after pancreaticoduodenectomy (PD). One possible method to assess pancreatic texture and atrophy, is via computed tomography (CT) scan of the abdomen. The purpose of our study was to evaluate the relation between the preoperative CT scan and the incidence of pancreatic fistula after PD. Methods: A retrospective single-center study including patients who underwent PD for a benign and malignant tumor of the periampullary region between the years 2000 and 2016. Demographic and imaging data were analysed and a correlation with the post-operative leak was evaluated. Results: Pancreatic leak was documented in 34 out of 154 (22.1%) patients. All the leakage cases occurred in the preserved pancreas group (33.1% of the total preserved pancreas group alone). No leak was documented in the atrophic pancreas group. This difference between the two groups was found to be statistically significant (p ≤ 0.00001). Conclusions: Atrophic pancreas in the preoperative CT scan may be protective against leakage after PD. These findings may help the surgeon to risk stratify patients accordingly. In addition, the findings suggest that patients with a preserved pancreas may require more protective methods to prevent leakage.

Characterization and Evaluation of Injectable Biodegradable Polymer Multimodality Radiologic Markers in an In Vivo Murine Model.

Biodegradable polymer clips as multidimensional soft tissue biopsy markers were developed with better biocompatibility and imaging features. Unlike the commercially available metallic biopsy markers, the developed polymer clips are temporary implants with similar efficacies as metal markers in imaging and detection and get absorbed within the body with time. Herein, we evaluate the degradation rate of three resorbable polymer-based marker compounds in an in vivo murine model. Three polymers, abbreviated as Polymer A (PLGA poly(lactic-co-glycolic acid)50:50), Polymer B (PLGA (poly(lactic-co-glycolic acid)) 75:25), and Polymer C (polycaprolactone (PCL)), mixed with 20% lipiodol and 0.2% iron oxide and a control polymer were implanted into nine mice, followed by CT and MRI imaging. Images were evaluated for conspicuity. Specimens were examined for tissue analysis of iodine and iron contents. Significant differences in polymer resorption and visualization on CT were noted, particularly at 8 weeks (p < 0.027). Polymers A, B, and C were visible by CT at 4, 6, and 8 weeks, respectively. All marker locations were detected on MRI (T1 and SWI) after 24 weeks, with tattooing of the surrounding soft tissue by iron deposits. CT and MR visible polymer markers can be constructed to possess variable resorption, with stability ranging between 4 and 14 weeks post placement, making this approach suitable for distinct clinical scenarios with varying time points.

Accumulation of 3-aminopropylphosphonate in the ex vivo brain observed by phosphorus-31 nuclear magnetic resonance.

3-aminopropylphosphonate (3-APP) is known for its use as an exogenous indicator of extracellular volume and pH in phosphorus-31 nuclear magnetic resonance (31 P NMR) studies. We used 3-APP for estimating the extracellular volume in NMR studies of several ex vivo preparations including retrograde perfused mouse heart (n = 4), mouse liver slices (n = 2), xenograft breast cancer tumors (n = 7, MCF7), and rat brain slices (n = 4). In the former three preparations, the 3-APP signal was stable in lineshape and intensity for hours and the chemical shift of the signal in the presence of the biological sample was the same as in the perfusion medium without the biological sample. However, in studies of brain slices, the 3-APP signal appeared split into two, with an upfield component (0.7 ± 0.1 ppm to the left) increasing with time and showing a wider linewidth (66.7 ± 12.6 vs. 39.1 ± 7.6 Hz, the latter is of the perfusion medium signal). This finding suggests that 3-APP inadvertently accumulated in brain slices, most likely as a membrane bound form. This observation limits the use of 3-APP as an inert biochemical indicator in brain preparations and should be taken into account when using 3-APP in vivo.

Ultrasonographic features can predict outcome of conservative management of acute appendicitis in children.

PURPOSE: To determine whether specific ultrasonographic features can predict failure of conservative treatment of acute appendicitis. METHODS: A 2-year retrospective study was conducted on children admitted with acute appendicitis. Those with uncomplicated appendicitis diagnosed solely by ultrasound, and treated conservatively, were followed 18-24 m to assess treatment outcome. Management was considered successful if recurrent acute appendicitis was not observed during follow-up. Appendix diameter, wall thickness, presence of mucosal ulceration, hyperechogenic fat, free fluid, and lymph nodes were evaluated as potential discriminatory ultrasonographic predictors. T-tests, chi-square, sensitivity, specificity, and odds ratios were calculated. RESULTS: Out of 556 consecutive patients that were admitted with acute appendicitis, 180 (32%) managed conservatively. One hundred eleven (62%) imaged by US only. Ninety-two out of 111 (83%) were followed 18-24 m to assess treatment outcome, and 19/111 (17%) were lost to follow-up. Conservative management was successful in 72/92 (78.2%), with treatment failure in 20/92 (21.8%) (5/92 (5.4%) with recurrent acute appendicitis and 15/92 (16.3%) underwent appendectomy). Of the ultrasonographic features studied, mucosal ulceration demonstrated statistically significant predictive value. Fifteen out of 20 (75%) treatment failures had mucosal ulceration, compared to 21/72 (29.2%) of the patients with successful treatment (p < 0.001). This yielded a positive odds ratio of 7.3 (2.3-22.6, 95% CI), 70.8% (58.9-80.9, 95% CI) specificity, and 75% (50.9-91.3, 95% CI) sensitivity. Positive predictive value was 41.6% (31.5-52.5, 95% CI) while intact mucosa had negative predictive value of 91% (82.4-95.6, 95% CI) for conservative management success. CONCLUSION: The presence or absence of appendiceal mucosal ulceration at ultrasound can predict conservative management outcome in the setting of acute appendicitis, potentially improving pediatric patient selection for conservative management.

Randomised clinical trial: A phase 2 double-blind study of namodenoson in non-alcoholic fatty liver disease and steatohepatitis.

BACKGROUND: Namodenoson, an A3 adenosine receptor (A3AR) agonist, improved liver function/pathology in non-alcoholic steatohepatitis (NASH) preclinical models. AIM: To evaluate the efficacy and safety of namodenoson for the treatment of non-alcoholic fatty liver disease (NAFLD) with or without NASH METHODS: This phase 2 study included 60 patients with NAFLD (ALT ≥60 IU/L) who were randomised (1:1:1) to oral namodenoson 12.5 mg b.d. (n = 21), 25 mg b.d. (n = 19), or placebo (n = 20) for 12 weeks (total follow-up: 16 weeks). The main efficacy endpoint involved serum ALT after 12 weeks of treatment. RESULTS: Serum ALT decreased over time with namodenoson in a dose-dependent manner. The difference between change from baseline (CFB) for ALT in the namodenoson 25 mg b.d. arm vs placebo trended towards significance at 12 weeks (P = 0.066). Serum AST levels also decreased with namodenoson in a dose-dependent manner; at 12 weeks, the CFB for 25 mg b.d. vs placebo was significant (P = 0.03). At Week 12, 31.6% in the namodenoson 25 mg b.d. arm and 20.0% in the placebo arm achieved ALT normalisation (P = 0.405). At week 16, the respective rates were 36.8% and 10.0% (P = 0.038). A3AR expression levels were stable over time across study arms. Both doses of namodenoson were well tolerated with no drug-emergent severe adverse events, drug-drug interactions, hepatotoxicity, or deaths. Three adverse events were considered possibly related to study treatment: myalgia (12.5 mg b.d. arm), muscular weakness (25 mg b.d. arm), and headache (25 mg b.d. arm). CONCLUSION: A3AR is a valid target; namodenoson 25 mg b.d. was safe and demonstrated efficacy signals (ClinicalTrials.gov #NCT02927314).

Dual energy CT in acute appendicitis: value of low mono-energy.

OBJECTIVES: To assess the potential role of low monoenergetic images in the evaluation of acute appendicitis. METHODS: A retrospective study of 42 patients with pathology proven acute appendicitis underwent contrast-enhanced-CT conducted on a single-source-DECT before surgery. Attenuation, SNR, and CNR were calculated on both monoenergetic and conventional images and compared to 24 abdominal CT-scans with normal appendix. Representative conventional and monoenergetic images were randomized and presented side-by-side to three abdominal radiologists to determine preferred images for detecting inflammation. Additionally, six individual acute inflammatory characteristics were graded on a 1-5 scale to determine factors contributing to differences between conventional and monoenergetic images by 2 abdominal radiologists. Paired t-tests, Wilcoxon and McNemar tests, and intra-observer error statistics were performed. RESULTS: For the inflamed appendixes monoenergetic images had overall increased attenuation (average ratio 1.7; P < 0.05), signal-to-noise-ratio (6.7 ± 3.1 vs 4.2 ± 1.6; P < 0.001) and contrast-to-noise-ratio (12.1 ± 3 vs 9 ± 2.1; P < 0.001). Moreover, this increase was not found in normal appendixes (P < 0.001 vs p = 0.28-0.44). Subjectively, radiologists showed significant preferences towards monoenergetic images (P < 0.001), with inter-reader agreement of 0.84. Two parameters, diffuse bowel wall and mucosal enhancement, received significantly higher scores on monoenergetic images (average 4.3 vs. 3.0; P < 0.001 and 2.8 vs. 2.3 P < 0.03 respectively, with interobserver agreements of 62% and 52%). CONCLUSION: Increased bowel wall conspicuity from enhanced attenuation, SNR, and CNR on low monenergetic CT images results in a significant preference by radiologists for these images when assessing acute inflamed appendixes. Thus, close inspection of low monoenergetic images may improve the visualization of acute inflammatory bowel processes.

LDH and PDH Activities in the Ischemic Brain and the Effect of Reperfusion-An Ex Vivo MR Study in Rat Brain Slices Using Hyperpolarized [1-13C]Pyruvate.

Ischemic stroke is a leading cause for neurologic disability worldwide, for which reperfusion is the only available treatment. Neuroimaging in stroke guides treatment, and therefore determines the clinical outcome. However, there are currently no imaging biomarkers for the status of the ischemic brain tissue. Such biomarkers could potentially be useful for guiding treatment in patients presenting with ischemic stroke. Hyperpolarized 13C MR of [1-13C]pyruvate is a clinically translatable method used to characterize tissue metabolism non-invasively in a relevant timescale. The aim of this study was to utilize hyperpolarized [1-13C]pyruvate to investigate the metabolic consequences of an ischemic insult immediately during reperfusion and upon recovery of the brain tissue. The rates of lactate dehydrogenase (LDH) and pyruvate dehydrogenase (PDH) were quantified by monitoring the rates of [1-13C]lactate and [13C]bicarbonate production from hyperpolarized [1-13C]pyruvate. 31P NMR of the perfused brain slices showed that this system is suitable for studying ischemia and recovery following reperfusion. This was indicated by the levels of the high-energy phosphates (tissue viability) and the chemical shift of the inorganic phosphate signal (tissue pH). Acidification, which was observed during the ischemic insult, has returned to baseline level following reperfusion. The LDH/PDH activity ratio increased following ischemia, from 47.0 ± 12.7 in the control group (n = 6) to 217.4 ± 121.3 in the ischemia-reperfusion group (n = 6). Following the recovery period (ca. 1.5 h), this value had returned to its pre-ischemia (baseline) level, suggesting the LDH/PDH enzyme activity ratio may be used as a potential indicator for the status of the ischemic and recovering brain.

CT severity indices derived from low monoenergetic images at dual-energy CT may improve prediction of outcome in acute pancreatitis.

OBJECTIVES: To determine whether imaging features and severity indices using low monoenergetic DECT images improve diagnostic conspicuity and outcome prediction in acute pancreatitis compared to conventional images. METHODS: A retrospective study of patients with clinical and radiographic signs of acute pancreatitis who underwent 50 contrast-enhanced CT exams conducted on a single-source DECT was performed. Representative conventional and 50 keV-monoenergetic images were randomized and presented to four abdominal radiologists to determine preferred imaging for detecting fat stranding and parenchymal inflammation. Contrast and signal-to-noise ratios were constructed for necrotic, hypoattenuated, inflamed, and healthy parenchyma. These parameters and the CT severity index (CTSI) were compared between conventional and low monoenergetic images using paired t tests and correlated to clinical outcome. RESULTS: Although preference for conventional images was noted for subtle peri-pancreatic fat stranding (169/200 (85%) reads), there was clear preference for low monoenergetic images among all readers for pancreatic inflammation evaluation (188/200 (94%) reads). Moreover, identification of small, hypoattenuating inflammatory foci on monoenergetic images alone in 13/50 (26%) cases resulted in upstaged CTSI from mild to moderate in 7/50 (14%), associated with longer hospitalization (16 ± 17 days vs. 5 ± 2 days; p < 0.05), ICU admission, and drainage. Quantitatively, a twofold difference between normal and inflamed parenchyma attenuation was identified for monoenergetic (44.8 ± 27.6) vs. conventional (25.1 ± 14.7) images (p < 0.05). Significant increases were seen in the monoenergetic SNR and CNR compared to the conventional images (p < 0.05). CONCLUSIONS: DECT low monoenergetic images afford better tissue assessment and demarcation of inflamed pancreatic parenchyma. Additionally, they provide improved characterization of the extent parenchymal necrosis, enabling better classification that may better predict severe clinical outcomes. KEY POINTS: • DECT low monoenergetic images afford better tissue assessment and demarcation of inflamed pancreatic parenchyma and provide improved characterization of the extent parenchymal necrosis. • Qualitatively, low monoenergetic images were preferred over conventional DECT images for the evaluation of pancreatic inflammation; and quantitatively, there is a twofold difference between normal and inflamed parenchyma attenuation, SNR, and CNR between monoenergetic vs. conventional images. • Monoenergetic imaging identified additional small, hypoattenuating inflammatory foci in 26% resulting in an upstaged CT severity index in 14% associated with longer hospitalization, ICU admission, and drainage, thereby enabling better classification and better prediction of severe clinical outcomes.

Psoas Attenuation and Mortality of Elderly Patients Undergoing Nontraumatic Emergency Laparotomy.

BACKGROUND: Emergency laparotomy (EL) is an increasingly common procedure in the elderly. Factors associated with mortality in the subpopulation of frail patients have not been thoroughly investigated. Sarcopenia has been investigated as a surrogate for frailty and poor prognosis. Our primary aim was to evaluate the association between easily measured sarcopenia parameters and 30-day postoperative mortality in elderly patients undergoing EL. Length of stay (LOS) and admission to an intensive care unit were secondary end points. METHODS: We conducted a retrospective cohort study, over a 5-year period, of patients aged 65 y and older who underwent EL at a tertiary university hospital. Sarcopenia was evaluated on admission computed tomography scan by two methods, first by psoas muscle attenuation and second by the product of perpendicular cross-sectional diameters (PCSDs). The lowest quartile of PCSDs and attenuation were defined as sarcopenic and compared with the rest of the cohort. Attenuation was stratified for the use of contrast enhancement. Multivariant logistic regression was performed to determine independent risk factors. RESULTS: During the study period, 403 patients, older than 65 y, underwent EL. Of these, 283 fit the inclusion criteria and 65 (23%) patients died within 30 d of surgery. On bivariate analysis, psoas muscle attenuation, but not PCSDs, was found to be associated with 30-day mortality (OR = 2.43, 95% CI = 1.34-4.38, P = 0.003) and longer LOS (35.7 d versus 22.2 d, Δd 13.5, 95% CI = 6.4-20.7, P < 0.001). In a multivariate analysis, psoas muscle attenuation, but not PCSDs, was an independent risk factor for 30-day postoperative mortality (OR = 2.35, 95% CI = 1.16-4.76, P = 0.017) and longer LOS (Δd = 14.4, 95% CI = 7.7-21.0, P < 0.001). Neither of the sarcopenia parameters was associated with increased admission to an intensive care unit. DISCUSSION: Psoas muscle attenuation is an independent risk factor for 30-day postoperative mortality and LOS after EL in the elderly population. This measurement can inform clinicians about the operative risk and hospital resource utilization.