Metabolic imaging of human embryos is predictive of ploidy status but is not associated with clinical pregnancy outcomes: a pilot trial.

STUDY QUESTION: Does fluorescence lifetime imaging microscopy (FLIM)-based metabolic imaging assessment of human blastocysts prior to frozen transfer correlate with pregnancy outcomes? SUMMARY ANSWER: FLIM failed to distinguish consistent patterns in mitochondrial metabolism between blastocysts leading to pregnancy compared to those that did not. WHAT IS KNOWN ALREADY: FLIM measurements provide quantitative information on NAD(P)H and flavin adenine dinucleotide (FAD+) concentrations. The metabolism of embryos has long been linked to their viability, suggesting the potential utility of metabolic measurements to aid in selection. STUDY DESIGN, SIZE, DURATION: This was a pilot trial enrolling 121 IVF couples who consented to have their frozen blastocyst measured using non-invasive metabolic imaging. After being warmed, 105 couples' good-quality blastocysts underwent a 6-min scan in a controlled temperature and gas environment. FLIM-assessed blastocysts were then transferred without any intervention in management. PARTICIPANTS/MATERIALS, SETTING, METHODS: Eight metabolic parameters were obtained from each blastocyst (4 for NAD(P)H and 4 for FAD): short and long fluorescence lifetime, fluorescence intensity, and fraction of the molecule engaged with enzyme. The redox ratio (intensity of NAD(P)H)/(intensity of FAD) was also calculated. FLIM data were combined with known metadata and analyzed to quantify the ability of metabolic imaging to differentiate embryos that resulted in pregnancy from embryos that did not. De-identified discarded aneuploid human embryos (n = 158) were also measured to quantify correlations with ploidy status and other factors. Statistical comparisons were performed using logistic regression and receiver operating characteristic (ROC) curves with 5-fold cross-validation averaged over 100 repeats with random sampling. AUC values were used to quantify the ability to distinguish between classes. MAIN RESULTS AND THE ROLE OF CHANCE: No metabolic imaging parameters showed significant differences between good-quality blastocysts resulting in pregnancy versus those that did not. A logistic regression using metabolic data and metadata produced an ROC AUC of 0.58. In contrast, robust AUCs were obtained when classifying other factors such as comparison of Day 5 (n = 64) versus Day 6 (n = 41) blastocysts (AUC = 0.78), inner cell mass versus trophectoderm (n = 105: AUC = 0.88) and aneuploid (n = 158) versus euploid and positive pregnancy embryos (n = 108) (AUC = 0.82). LIMITATIONS, REASONS FOR CAUTION: The study protocol did not select which embryo to transfer and the cohort of 105 included blastocysts were all high quality. The study was also limited in number of participants and study sites. Increased power and performing the trial in more sites may have provided a stronger conclusion regarding the merits of the use of FLIM clinically. WIDER IMPLICATIONS OF THE FINDINGS: FLIM failed to distinguish consistent patterns in mitochondrial metabolism between good-quality blastocysts leading to pregnancy compared to those that did not. Blastocyst ploidy status was, however, highly distinguishable. In addition, embryo regions and embryo day were consistently revealed by FLIM. While metabolic imaging detects mitochondrial metabolic features in human blastocysts, this pilot trial indicates it does not have the potential to serve as an effective embryo viability detection tool. This may be because mitochondrial metabolism plays an alternative role post-implantation. STUDY FUNDING/COMPETING INTEREST(S): This study was sponsored by Optiva Fertility, Inc. Boston IVF contributed to the clinical site and services. Becker Hickl, GmbH, provided the FLIM system on loan. T.S. was the founder and held stock in Optiva Fertility, Inc., and D.S. and E.S. had options with Optiva Fertility, Inc., during this study. TRIAL REGISTRATION NUMBER: The study was approved by WCG Connexus IRB (Study Number 1298156).

An Overview of Computational Coronary Physiology Technologies Based on Medical Imaging and Artificial Intelligence.

This article reviews four new technologies for assessment of coronary hemodynamics based on medical imaging and artificial intelligence, including quantitative flow ratio (QFR), optical flow ratio (OFR), computational fractional flow reserve (CT-FFR) and artificial intelligence (AI)-based instantaneous wave-free ratio (iFR). These technologies use medical imaging such as coronary angiography, computed tomography angiography (CTA), and optical coherence tomography (OCT), to reconstruct three-dimensional vascular models through artificial intelligence algorithms, simulate and calculate hemodynamic parameters in the coronary arteries, and achieve non-invasive and rapid assessment of the functional significance of coronary stenosis. This article details the working principles, advantages such as non-invasiveness, efficiency, accuracy, limitations such as image dependency, and assumption restrictions, of each technology. It also compares and analyzes the image dependency, calculation accuracy, calculation speed, and operation simplicity, of the four technologies. The results show that these technologies are highly consistent with the traditional invasive wire method, and shows distinct advantages in terms of accuracy, reliability, convenience and cost-effectiveness, but there are also factors that affect accuracy. The results of this review demonstrates that AI-based iFR technology is currently one of the most promising technologies. The main challenges and directions for future development are also discussed. These technologies bring new ideas for the non-invasive assessment of coronary artery disease, and are expected to promote the technological progress in this field.

Speech changes in old age: Methodological considerations for speech-based discrimination of healthy ageing and Alzheimer's disease.

BACKGROUND: Recent evidence suggests that speech substantially changes in ageing. As a complex neurophysiological process, it can accurately reflect changes in the motor and cognitive systems underpinning human speech. Since healthy ageing is not always easily discriminable from early stages of dementia based on cognitive and behavioural hallmarks, speech is explored as a preclinical biomarker of pathological itineraries in old age. A greater and more specific impairment of neuromuscular activation, as well as  a specific cognitive and linguistic impairment in dementia, unchain discriminating changes in speech. Yet, there is no consensus on such discriminatory speech parameters, neither on how they should be elicited and assessed. AIMS: To provide a state-of-the-art on speech parameters that allow for early discrimination between healthy and pathological ageing; the aetiology of these parameters; the effect of the type of experimental stimuli on speech elicitation and the predictive power of different speech parameters; and the most promising methods for speech analysis and their clinical implications. METHODS & PROCEDURES: A scoping review methodology is used in accordance with the PRISMA model. Following a systematic search of PubMed, PsycINFO and CINAHL, 24 studies are included and analysed in the review. MAIN CONTRIBUTION: The results of this review yield three key questions for the clinical assessment of speech in ageing. First, acoustic and temporal parameters are more sensitive to changes in pathological ageing and, of these two, temporal variables are more affected by cognitive impairment. Second, different types of stimuli can trigger speech parameters with different degree of accuracy for the discrimination of clinical groups. Tasks with higher cognitive load are more precise in eliciting higher levels of accuracy. Finally, automatic speech analysis for the discrimination of healthy and pathological ageing should be improved for both research and clinical practice. CONCLUSIONS & IMPLICATIONS: Speech analysis is a promising non-invasive tool for the preclinical screening of healthy and pathological ageing. The main current challenges of speech analysis in ageing are the automatization of its clinical assessment and the consideration of the speaker's cognitive background during evaluation. WHAT THIS PAPER ADDS: What is already known on the subject Societal aging  goes hand in hand with the rising incidence of ageing-related neurodegenerations, mainly Alzheimer's disease (AD). This is particularly noteworthy in countries with longer life expectancies. Healthy ageing and early stages of AD share a set of cognitive and behavioural characteristics. Since there is no cure for dementias, developing methods for accurate discrimination of healthy ageing and early AD is currently a priority. Speech has been described as one of the most significantly impaired features in AD. Neuropathological alterations in motor and cognitive systems would underlie specific speech impairment in dementia. Since speech can be evaluated quickly, non-invasively and inexpensively, its value for the clinical assessment of ageing itineraries may be particularly high. What this paper adds to existing knowledge Theoretical and experimental advances in the assessment of speech as a marker of AD have developed rapidly over the last decade. Yet, they are not always known to clinicians. Furthermore, there is a need to provide an updated state-of-the-art on which speech features are discriminatory to AD, how they can be assessed, what kind of results they can yield, and how such results should be interpreted. This article provides an updated overview of speech profiling, methods of speech measurement and analysis, and the clinical power of speech assessment for early discrimination of AD as the most common cause of dementia. What are the potential or actual clinical implications of this work? This article provides an overview of the predictive potential of different speech parameters in relation to AD cognitive impairment. In addition, it discusses the effect that the cognitive state, the type of elicitation task and the type of assessment method may have on the results of the speech-based analysis in ageing.

Transient Elastography Is the Best-Performing Non-Invasive Test of Liver Fibrosis in Obese Asian Patients with Non-Alcoholic Fatty Liver Disease: A Pilot, Cross-Sectional Study.

Background and Objectives: The prevalence of NAFLD (non-alcoholic fatty liver disease) is increasing, and up to 64% of Asian patients with NAFLD are obese. Non-invasive tests (NITs) for the assessment of liver fibrosis are increasingly being used, but data on their performance in obese Asian patients are lacking. In this pilot cross-sectional study, we aim to compare the distribution of serum and radiological markers of fibrosis between obese Asian biopsy-proven NAFLD patients with and without fibrosis and estimate the diagnostic accuracies of these indices. Materials and Methods: Obese Asian patients with NAFLD and who had undergone a liver biopsy showing histological evidence of NAFLD were invited to participate. Liver fibrosis was assessed using laboratory (APRI, AAR, BARD, FIB4, NFS, and Asia-Pacific NAFLD advanced fibrosis score) and imaging modalities (TE: transient elastography, MRE: magnetic resonance elastography, and SWU: shear wave ultrasonography). Results: A total of 16 patients were included in the final analysis. On liver biopsy, nine patients (56.3%) had significant fibrosis (F2 or higher), and six of these patients had advanced fibrosis (F3 or higher). F4 fibrosis was present in one patient (6.3%). For the laboratory markers, we found that the BARD score correctly identified five out of six patients with advanced fibrosis (83.4%, p value 0.045). Among all the NITs studied, liver stiffness measured by TE had the highest accuracy of 87.5% in its established threshold of 8.5 kPa for the detection of advanced fibrosis. MRE also performed well (81.2% in 3.64 kPa). Conclusions: In conclusion, TE has performed well in the detection of advanced fibrosis in obese Asian patients with biopsy-proven NAFLD in our pilot study. Further large-scale definitive studies are needed to validate the results of our findings.

Quantitative T2 mapping monitoring the maturation of engineered elastic cartilage in a rabbit model.

BACKGROUND: Cartilage tissue engineering provides a promising approach to reconstruct craniofacial defects, and a noninvasive method is needed to assess its effectiveness. Although magnetic resonance imaging (MRI) has been used to evaluate articular cartilage in vivo, few studies focused on its feasibility in monitoring engineered elastic cartilage (EC). METHODS: Auricular cartilage, silk fibroin (SF) scaffold, and EC consisting of rabbit auricular chondrocytes and SF scaffold were transplanted subcutaneously into the rabbit back. In eight weeks after transplantation, grafts were imaged by MRI using PROSET, PDW VISTA SPAIR, 3D T2 VISTA, 2D MIXED T2 Multislice, and SAG TE multiecho sequences, followed by histological examination and biochemical analysis. Statistical analyses were performed to identify the association between T2 values and biochemical indicator values of EC. RESULTS: In vivo imaging shows that 2D MIXED T2 Multislice sequence (T2 mapping) clearly distinguished the native cartilage, engineered cartilage and fibrous tissue. T2 values showed high correlations with cartilage-specific biochemical parameters at different time points, especially the elastic cartilage specific protein elastin (ELN, r= -0.939, P < 0.001). CONCLUSION: Quantitative T2 mapping can effectively detect the in vivo maturity of engineered elastic cartilage after subcutaneously transplantation. This study would promote the clinical application of MRI T2 mapping in monitoring engineered elastic cartilage in the repair of craniofacial defects.

Non-invasive oocyte quality assessment.

Oocyte quality is perhaps the most important limiting factor in female fertility; however, the current methods of determining oocyte competence are only marginally capable of predicting a successful pregnancy. We aim to review the predictive value of non-invasive techniques for the assessment of human oocytes and their related cells and biofluids that pertain to their developmental competence. Investigation of the proteome, transcriptome, and hormonal makeup of follicular fluid, as well as cumulus-oocyte complexes are currently underway; however, prospective randomized non-selection-controlled trials of the future are needed before determining their prognostic value. The biological significance of polar body morphology and genetics are still unknown and the subject of debate. The predictive utility of zygotic viscoelasticity for embryo development has been demonstrated, but similar studies performed on oocytes have yet to be conducted. Metabolic profiling of culture media using human oocytes are also limited and may require integration of automated, high-throughput targeted metabolomic assessments in real time with microfluidic platforms. Light exposure to oocytes can be detrimental to subsequent development and utilization of time-lapse imaging and morphometrics of oocytes is wanting. Polarized light, Raman microspectroscopy, and coherent anti-Stokes Raman scattering are a few novel imaging tools that may play a more important role in future oocyte assessment. Ultimately, the integration of chemistry, genomics, microfluidics, microscopy, physics, and other biomedical engineering technologies into the basic studies of oocyte biology, and in testing and perfecting practical solutions of oocyte evaluation, are the future for non-invasive assessment of oocytes.

Non-invasive assessment of liver abnormalities in pediatric Fontan patients.

Liver abnormalities are well known among long-term survivors of Fontan palliation, which remains the definite surgery for complex congenital heart disease and single ventricle physiology. Pediatric data however are scarce. We assessed the prevalence and degree of liver abnormalities in pediatric Fontan patients through non-invasive investigations suitable for longitudinal follow-up. Thirty-five patients with a median age of 11.8 years (5.2-16.6) and median time since Fontan of 6 years (1.17-13.83) were studied. Each child underwent a blood test, liver Doppler ultrasound (US), and transient elastography (TE). Healthy children were used as controls for TE measurement. AST, ALT, γGT, and direct bilirubin were abnormal in respectively 12 (34%), 5 (14%), 24 (69%), and 7 (20%) patients, while platelet count was decreased in 7 (20%). Splenomegaly was present in 7 (20%) patients. Portal vein mean flow velocity was < 15 cm/s in 19 (54%) patients indicative of portal hypertension. Twenty-two patients (63%) showed inferior vena cava collapsibility index values below 17%, indicating venous congestion. Hepatic artery and superior mesenteric artery resistance index were inversely correlated with time post Fontan (p < 0.05). TE values in Fontan patients were significantly higher than controls, with a median of 12.6 versus 4.6 kPa (p < 0.001) and were already increased shortly after Fontan completion. Conclusion: Liver abnormalities are frequently observed in pediatric Fontan patients. The non-invasive investigations used were not able to confirm liver fibrosis or differentiate hepatic congestion from fibrosis. Based on our findings, we propose a prospective screening protocol with serial measurements of laboratory, (Doppler) US, and TE parameters. What is Known: • Hepatic dysfunction is a well-known consequence of the Fontan circulation. • The natural history of Fontan-associated liver disease in the pediatric age group remains unclear. What is New: • Liver abnormalities are frequently observed in pediatric Fontan patients; however, differentiating liver fibrosis and hepatic congestion with non-invasive investigations remains challenging. Sonographic Doppler measurements may improve our insight in both Fontan-associated liver disease development and the functioning of the Fontan circulation. • A prospective screening protocol is proposed to improve our ability to detect Fontan-associated liver disease early on and understand its natural history.

Saturation oxygenation pressure index: a non-invasive bedside measure for severity of respiratory disease in neonates on CPAP.

The treatment of respiratory distress in neonates ranges from non-invasive continuous positive airway pressure (CPAP) to advanced invasive mechanical ventilation. Monitoring on CPAP is often done by calculating oxygenation after blood gas analysis which is an invasive procedure. Saturation oxygen pressure index (SOPI) is a simple, non-invasive, bedside tool to monitor the severity of respiratory illness in neonates on CPAP. This study was aimed at validation of SOP index against AaDO2 and determine the cut-off values of SOPI for A-aDO2 of 70, 85 and100. This was a prospective observational study on 126 neonates with respiratory distress and treated with CPAP. The correlation between SOPI and A-aDO2 was validated using Bootstrap method. There was a significant positive correlation between SOPI and A-aDO2 with the Spearman correlation coefficient (rho) being 0.815 (p = 0). The mean coefficient of correlation after Bootstrap was 0.827 (p value < 0.0001). SOPI values of 1.52, 1.57 and 1.6 predicted A-aDO2 value of 70, 85 and 100 with a sensitivity of above 80% and specificity above 90%, respectively.Conclusion: SOPI has a significant positive correlation of 82.7% against A-aDO2 and can be a valuable tool to assess respiratory distress in neonates without arterial blood gas. What is Known: • Saturation oxygen pressure index (SOPI) is a non-invasive monitoring tool for neonates on N-CPAP. • SOPI has a good correlation with AaDO2. What is New: • Correlation of SOPI with AaDO2 is now validated. • Values between 1.52 and 1.88 indicate clinically useful range of AaDO2 for escalation of respiratory support from CPAP.

Combination antiretroviral therapy is associated with reduction in liver fibrosis scores in patients with HIV and HBV co-infection.

BACKGROUND: Liver fibrosis is common in individuals with HIV/HBV co-infection, but whether cART could reverses liver fibrosis is unclear. METHODS: This was a retrospective observational study. Binary logistic regression was used to assess predictors of liver fibrosis in individuals with HIV/HBV co-infection. Comparison of FIB-4 scores before and after cART were compared using X2 test and t test. RESULTS: Four hundred and fifty-eight individuals with HIV/HBV co-infection were included in this study. It was found that cART (HR 0.016, 95% CI: 0.009-0.136; P < 0.001) was one of protection factors to against liver fibrosis. Forty individuals who had normal levels of ALT, AST and PLT during the whole course of diseases were stratified into FIB-4 < 1.45 (n = 14), 1.45 ≤ FIB-4 ≤ 3.25 (n = 19) and FIB-4 > 3.25 (n = 7) groups by their FIB-4 scores before cART. In 1.45 ≤ FIB-4 ≤ 3.25 group, 57.9%(11/19) of the individuals dropped to FIB-4 < 1.45 group by cART; in FIB-4 > 3.25 group, 85.7%(6/79) dropped to 1.45 ≤ FIB-4 ≤ 3.25 group, while 14.3%(1/7) dropped to FIB-4 < 1.45 group. In cART-naive group, 1 year, 2-5 years and 5-10 years post-cART groups, FIB-4 scores were 4.29 ± 0.43, 3.63 ± 0.38, 2.90 ± 0.36 and 2.52 ± 0.38, respectively (P = 0.034); and the incidence of liver fibrosis were 7.38%(104/141), 63.6%(98/154), 60.8%(62/102) and 47.5%(29/61), respectively (P = 0.004). CONCLUSION: cART was associated with decreased FIB-4 scores and the benefit of cART in reversing liver fibrosis can sustain for a decade in patients with HIV/HBV co-infection.

Ultrasound Elastography-Cornerstone of Non-Invasive Metabolic Dysfunction-Associated Fatty Liver Disease Assessment.

Metabolic dysfunction-associated fatty liver disease has become the most common chronic liver disease as well as the most common cause for liver transplantation. With its different methods types, elastography of the liver can be used for non-invasive evaluation of the liver fibrosis and steatosis degree. The article focuses on the description, use, advantages, and limitations of the currently known elastographic techniques. It proposes a simple risk assessment algorithm for the liver fibrosis progress evaluation. The following is an overview of the use of liver and spleen elastography in the detection of clinically relevant portal hypertension. It concludes with research and technological possibilities that could be important to the field in the upcoming years.

Assessing Baveno VI criteria with liver stiffness measured using a new point-shear wave elastography technique (BAVElastPQ study).

BACKGROUND AND AIMS: To date, no study has explored the potential role of ElastPQ, a novel point-SWE technique, in the assessment of clinically significant portal hypertension. The aim of our study was to determine a liver stiffness (LS) cut-off value measured by ElastPQ and laboratory parameters that could help to identify those patients who can safely avoid screening endoscopy. METHODS: Data were collected on 1422 patients who underwent ElastPQ measurement from January 2013 to January 2016 in our Department. Inclusion criteria were a LS value of ≥7 kPa, an upper gastrointestinal endoscopy within 12 months and a diagnosis of compensated chronic liver disease. Exclusion criteria were history of decompensated liver disease, evidence of porto-spleno-mesenteric vein thrombosis and non-cirrhotic portal hypertension. Varices were graded as low-risk varices (grade <2) or varices needing treatment (VNT, grade ≥2). RESULTS: The study included 195 patients (120 [61%] HCV, 171 [88%] Child-Pugh A). Varices were present in 35% cases, with 10% prevalence of VNT. According to ROC curve analysis, LS measurement and platelet count were evaluated as predictors of VNT. Overall, 75/195 (38%) met the 'BAVElastPQ' criteria (that is, LS < 12 kPa and platelet count >150 000/µL). Within this group, 11/75 (15%) had any grade of varices and only 1/75 (1%) had VNT. The BAVElastPQ criteria gave sensitivity of 0.95, specificity of 0.42, positive predictive value of 0.15 and negative predictive value of 0.99. CONCLUSIONS: The BAVElastPQ criteria correctly identified 99% of patients without VNT. By applying such criteria, we could have potentially avoided 38% of surveillance endoscopies in our cohort.

Controlled attenuation parameter by vibration-controlled transient elastography for steatosis assessment in members of the public undergoing regular health checkups with reference to magnetic resonance imaging-based proton density fat fraction.

AIM: Controlled attenuation parameter (CAP) measured by vibration-controlled transient elastography (FibroScan) allows repeatable and reliable assessment of liver steatosis for screening of patients at risk of non-alcoholic steatohepatitis development among asymptomatic individuals at a community level. However, this has never been compared with another quantitative method, such as magnetic resonance imaging-based proton density fat fraction, among the Chinese health checkup population. METHODS: A multicenter prospective study was conducted with Chinese individuals undergoing regular health checkups. Steatosis grading by magnetic resonance imaging-based proton density fat fraction was used as the reference to evaluate the diagnostic performance of CAP. RESULTS: A total of 173 individuals were included with mean age of 45 ± 11 years and body mass index of 25.8 ± 4.0 kg/m2 . A linear correlation was found between CAP and log10 -transformed magnetic resonance imaging-based proton density fat fraction results (Pearson's coefficient 0.772, P < 0.001). The areas under the receiver operating characteristic curve for distinguishing ≥S1 and ≥S2 steatosis were 0.88 (95% confidence interval 0.83-0.93) and 0.89 (95% confidence interval 0.83-0.95), respectively. When optimized for ≥90% sensitivity, the CAP cut-off for staging ≥S1 steatosis was 244 dB/m. CAP could classify patients with ≥S1 steatosis with similar performance as an ultrasound examination. CONCLUSIONS: As a non-invasive and quantitative method, CAP is highly adapted for population screening at a community level. With the integration of liver stiffness and CAP results in risk stratification scores for non-alcoholic steatohepatitis, vibration-controlled transient elastography can be useful in regular health checkups.

Non-invasive assessment of ICP in children: advances in ultrasound-based techniques.

The assessment of intracranial pressure (ICP) in children with neurological disease remains a cornerstone in their routine management. The quest for a reliable, reproducible and radiation-free non-invasive technique for assessing ICP in children remains somewhat of a holy grail for neurosurgery. This work assesses some of the recent advances in ultrasound-based techniques, addressing both novel processes and modifications aimed at improving the accuracy of existing techniques.

Chronic Granulomatous Disorder-Associated Colitis Can Be Accurately Evaluated with MRI Scans and Fecal Calprotectin Level.

PURPOSE: Colitis is a common and serious complication of chronic granulomatous disorder (CGD) and requires assessment. Colonoscopy is invasive and carries risks of serious complication. We therefore assessed non-invasive monitoring via magnetic resonance imaging (MRI). We also evaluated fecal calprotectin (FCP), the Harvey-Bradshaw index (HBI) clinical score, and serum cytokines. METHODS: We recruited 10 patients with CGD (8 males, mean age 29.6 years), scored a modified HBI, and obtained stool for FCP. The following day we took blood for cytokine measurement via Luminex, performed MR enterography (scored by two independent radiologists using three systems: London score, CDMI, and MaRIA) followed by colonoscopy with disease activity measurement via ulcerative colitis endoscopic index of severity (UCEIS). We assessed patient experience after each investigation and overall preference with follow-up questionnaires. RESULTS: MRI scores correlated well with colonoscopic gold standard (for London score R2 0.91, p < 0.0001; for CDMI R2 0.83, p = 0.0006; for MaRIA R2 0.89, p = 0.0002). MRI was better tolerated and generally preferred, quicker, and visualized the entire large bowel whereas colonoscopy did not reach the terminal ileum in 3 participants. Elevated FCP accurately differentiated patients with colitis from those without, and log(calprotectin) correlated well with disease activity (R2 0.71, p = 0.009). Serum interleukin (IL)-12 concentration correlated with colitis activity but IL-1ß and TNF did not. Harvey-Bradshaw index did not correlate with colitis activity. CONCLUSIONS: MRI and fecal calprotectin are useful methods for monitoring CGD colitis and should reduce the need for colonoscopy in these patients. IL-12 may represent an appropriate target for treatment.

Hepatic fat as clinical outcome and therapeutic target for nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is rapidly becoming the leading cause of advanced liver disease in Western countries. NAFLD is defined in the presence of increased hepatic fat content, which is mainly stored under the form of neutral lipids within intracellular droplets and is not explained by at risk alcohol intake. In order to understand the pathogenesis, monitor the progression and find novel treatments for this condition, previous research efforts mainly addressed the role of inflammation. However, very recent data seem to suggest that hepatic lipid accumulation may be involved in NAFLD pathogenesis by driving secondary inflammation and fibrosis progression. Here, we will briefly review the novel results derived from natural history, genetics, imaging studies and therapeutic trials that support the notion that hepatic fat accumulation may represent a major clinical outcome and therapeutic target for NAFLD. Indeed, prospective and genetic data are consistent with hepatic fat being a driver of NAFLD progression. Furthermore, new technologies will render possible to monitor hepatic fat content without the need of invasive assessment, thereby allowing to identify patients at higher risk, and to monitor the response to drugs that act by decreasing hepatic lipid accumulation.

Specificity of Myocardial Perfusion Imaging: Issues With Proposed MBS Item Review.

Myocardial perfusion scanning (MPS) is commonly used to assess patients with an intermediate to high risk of coronary artery disease. Concerns have been raised about the accuracy of this test. There is little recent data regarding the specificity of the MPS in the context of current medical therapy. The primary objective of this study is to determine the specificity of MPS in diagnosing obstructive coronary artery disease. A total of 184 patients fulfilled study criteria. The overall specificity of MPS for obstructive coronary artery disease was 54%.The only demographic variable that influenced specificity was gender: males with a specificity of 66% and females with a specificity of 29% (p-value=0.001). These results suggest that the real world specificity of MPS is lower than previously indicated, particularly in the female population. The limitations proposed by the Cardiac Services Committee Report are therefore unlikely to improve patient outcomes.

A new CFD based non-invasive method for functional diagnosis of coronary stenosis.

BACKGROUND: Accurate functional diagnosis of coronary stenosis is vital for decision making in coronary revascularization. With recent advances in computational fluid dynamics (CFD), fractional flow reserve (FFR) can be derived non-invasively from coronary computed tomography angiography images (FFRCT) for functional measurement of stenosis. However, the accuracy of FFRCT is limited due to the approximate modeling approach of maximal hyperemia conditions. To overcome this problem, a new CFD based non-invasive method is proposed. METHODS: Instead of modeling maximal hyperemia condition, a series of boundary conditions are specified and those simulated results are combined to provide a pressure-flow curve for a stenosis. Then, functional diagnosis of stenosis is assessed based on parameters derived from the obtained pressure-flow curve. RESULTS: The proposed method is applied to both idealized and patient-specific models, and validated with invasive FFR in six patients. Results show that additional hemodynamic information about the flow resistances of a stenosis is provided, which cannot be directly obtained from anatomy information. Parameters derived from the simulated pressure-flow curve show a linear and significant correlations with invasive FFR (r > 0.95, P < 0.05). CONCLUSION: The proposed method can assess flow resistances by the pressure-flow curve derived parameters without modeling of maximal hyperemia condition, which is a new promising approach for non-invasive functional assessment of coronary stenosis.

Aerial Mapping of Forests Affected by Pathogens Using UAVs, Hyperspectral Sensors, and Artificial Intelligence.

The environmental and economic impacts of exotic fungal species on natural and plantation forests have been historically catastrophic. Recorded surveillance and control actions are challenging because they are costly, time-consuming, and hazardous in remote areas. Prolonged periods of testing and observation of site-based tests have limitations in verifying the rapid proliferation of exotic pathogens and deterioration rates in hosts. Recent remote sensing approaches have offered fast, broad-scale, and affordable surveys as well as additional indicators that can complement on-ground tests. This paper proposes a framework that consolidates site-based insights and remote sensing capabilities to detect and segment deteriorations by fungal pathogens in natural and plantation forests. This approach is illustrated with an experimentation case of myrtle rust (Austropuccinia psidii) on paperbark tea trees (Melaleuca quinquenervia) in New South Wales (NSW), Australia. The method integrates unmanned aerial vehicles (UAVs), hyperspectral image sensors, and data processing algorithms using machine learning. Imagery is acquired using a Headwall Nano-Hyperspec ® camera, orthorectified in Headwall SpectralView ® , and processed in Python programming language using eXtreme Gradient Boosting (XGBoost), Geospatial Data Abstraction Library (GDAL), and Scikit-learn third-party libraries. In total, 11,385 samples were extracted and labelled into five classes: two classes for deterioration status and three classes for background objects. Insights reveal individual detection rates of 95% for healthy trees, 97% for deteriorated trees, and a global multiclass detection rate of 97%. The methodology is versatile to be applied to additional datasets taken with different image sensors, and the processing of large datasets with freeware tools.

[Present situation on non-invasive assessment of liver fibrosis/cirrhosis].

Patients with chronic liver disease often have varying degrees of hepatic fibrosis, and further exacerbations can lead to cirrhosis and even hepatocellular carcinoma. Liver biopsy is the gold standard for the diagnosis of liver fibrosis/cirrhosis, but there are still many limitations. In recent years, non-invasive assessments for liver fibrosis/cirrhosis have gained rapid development. Of these techniques, two different approaches have been validated in clinical practice: imaging methods based on the measurement of liver stiffness, and biological methods based on the serum biomarkers. The two different approaches can complement each other. Current non-invasive assessments for liver fibrosis/cirrhosis tend to be reliable for the detection of advanced fibrosis and cirrhosis, but often lack to distinguish the different early stage of liver fibrosis. Further improving the accuracy of non-invasive assessments might play an important role for clinical management of liver diseases.

Sitagliptin vs. placebo for non-alcoholic fatty liver disease: A randomized controlled trial.

BACKGROUND & AIMS: Uncontrolled studies show sitagliptin, an oral DPP-4 inhibitor, may improve alanine aminotransferase and liver histology in non-alcoholic fatty liver disease (NAFLD) patients. We aimed to compare sitagliptin vs. the efficacy of a placebo in reducing liver fat measured by MRI-derived proton density-fat fraction (MRI-PDFF). METHODS: This randomized, double-blind, allocation-concealed, placebo-controlled trial included 50 NAFLD patients with prediabetes or early diabetes randomized to sitagliptin orally 100mg/day or placebo for 24weeks. Primary outcome was liver fat change measured by MRI-PDFF in colocalized regions of interest within each of nine liver segments. Additional advanced assessments included MR spectroscopy (MRS) for internal validation of MRI-PDFF's accuracy, and magnetic resonance elastography (MRE) and FIBROSpect® II to assess liver fibrosis. RESULTS: Sitagliptin was not significantly better than placebo in reducing liver fat measured by MRI-PDFF (mean difference between sitagliptin and placebo arms: -1.3%, p=0.4). Compared to baseline, there were no significant differences in end-of-treatment MRI-PDFF for sitagliptin (18.1% to 16.9%, p=0.27) or placebo (16.6% to 14.0%, p=0.07). The groups had no significant differences for changes in alanine aminotransferase, aspartate aminotransferase, low-density lipoprotein, homeostatic model assessment insulin resistance, and MRE-derived liver stiffness. In both groups at baseline and post-treatment, MRI-PDFF and MRS showed robust correlation coefficients ranging from r(2)=0.96 to r(2)=0.99 (p<0.0001), demonstrating the strong internal validity of the findings. FIBROSpect® II showed no changes in the sitagliptin group but was significantly increased in the placebo group (p=0.03). CONCLUSIONS: Sitagliptin was safe but not better than placebo in reducing liver fat in prediabetic or diabetic patients with NAFLD. LAY SUMMARY: In a randomized, double-blind, placebo-controlled study, the anti-diabetic drug sitagliptin was no more effective than placebo for improving liver fat and liver fibrosis in patients with non-alcoholic fatty liver disease. This study demonstrates that non-invasive magnetic resonance imaging techniques, including magnetic resonance imaging-proton density-fat fraction and magnetic resonance elastography, can be used to assess treatment response in non-alcoholic fatty liver disease clinical trials.