Noninvasive Assessment Research Articles

Noninvasive minimal residual disease assessment in relapsed/refractory large B-cell lymphoma using digital droplet PCR.

Although several promising approaches for the treatment of relapsed/refractory diffuse large B-cell lymphoma (rrDLBCL) have been approved recently, it remains unclear which patients will ultimately achieve long-term responses. Circulating tumor (ct)DNA sequencing has emerged as a valuable tool to assess minimal residual disease (MRD). Correlations between MRD and outcomes have been shown in previously untreated DLBCL, but data on the repeated assessment of MRD in the dynamic course of rrDLBCL is limited. Here, we present an approach leveraging cost- and time-sensitivity of digital droplet (dd)PCR to repeatedly assess MRD in rrDLBCL and present proof-of-principle for its ability to predict outcomes.

Ultrasound-Based Prognostic Anatomical Parameters for Post-Prostatectomy Incontinence: A Systematic Review

Background: A number of assessment methods for the pelvic floor have been described. Male pelvic floor ultrasound is an accessible, noninvasive assessment tool. Objective: To evaluate current published literature on anatomical parameters on pre- and postoperative ultrasound imaging of the male pelvic floor and correlation with continence status following radical prostatectomy (RP). Methods: A comprehensive literature search was conducted using the PRISMA guidelines to identify publications up to November 2022. Exclusion criteria consisted of animal studies, non-English articles, case reports, reviews and abstracts or reports from conferences. A full-text review was performed on 12 papers using ultrasound to assess pelvic floor anatomy and correlation with continence status following RP. Results: A total of 18 anatomical parameters were evaluated using US. Membranous urethral length (MUL), striated urethral sphincter (SUS) morphology and activation were most commonly studied. Shorter pre- and postoperative MUL, decreased preoperative SUS thickness and vascularity, postoperative discontinuity of SUS muscle fibres and decreased SUS activation are associated with post-prostatectomy incontinence (PPI). There is a paucity of data comparing anatomical changes in men prior to and following RP. The benefits of transperineal ultrasound are that it is minimally invasive, accessible, provides dynamic imaging of all three striated muscle complexes simultaneously and includes a bony landmark to reference measures of pelvic floor muscle displacement. Conclusions: Ultrasound evaluation of the male pelvic floor is an evolving field as there is development in technology and understanding of pelvic floor anatomy. It is an accessible and dynamic imaging modality, which allows both morphological and functional assessment of pelvic floor anatomy and its role in PPI. MUL and SUS morphology and activation are associated with continence status following RP. Several other anatomical parameters that may predict PPI were identified. Current literature is limited by small, single-centre studies with heterogeneous cohorts and methodologies.

The influence of selected factors on wool cortisol concentration in alpacas (Vicugna pacos)

Several internal and external factors can influence animals’ hormonal activity. Cortisol level in hair and wool determines chronic stress, which is connected with the long-term HPA axis effect. Wool cortisol levels in alpacas have never been determined to this time. The study aimed to assess the influence of selected factors on wool cortisol concentration in alpacas. The study included 36 alpacas. Wool samples were collected during shearing in June 2021, cut with an electric clipper from the right shoulder and the rump. Wool samples were fragmented into proximal (winter-spring regrowth) and distal (summer-fall regrowth) segments. Alpacas’ Heat Stress Index (HSI) for the summer of 2020 was 139.4, and 116 for the winter of 2021. The cortisol levels in the wool samples were determined with the General Cortisol ELISA Kit assay.The most significant differences in wool cortisol concentrations were caused by two factors: the wool segment (P < 0.001; η2 = 0.889) and the region on the body (P < 0.001; η2 = 0.876). Wool cortisol level was higher in the distal segment (referring to the summer-fall season) than in the proximal one (referring to the winter-spring season). It is suggested that alpacas can feel heat stress in summer (HSI = 139.4), which could influence higher cortisol levels in the distal segment. The wool cortisol level was higher in the rump samples than the shoulder ones. Therefore, it is essential in future studies that wool samples from all tested animals should be completed from the same body region. Differences among age and sex groups were also observed. Wool cortisol level was higher in older animals, as differences between age groups were observed in samples from the rump in the distal and proximal segments (distal, the rump younger*older: P < 0.001; η2 = 0.321; proximal, the rump older*younger: P = 0.007; η2 = 0.195). Males showed higher cortisol levels than females, as a difference between sexes was observed in samples from the rump in the proximal segment (P = 0.001, η2 = 0.271). This study emphasizes that various factors may significantly influence wool cortisol levels, which can be helpful in alpacas’ welfare estimation using this hormonal indicator as a noninvasive long-term stress assessment method.

Simulated microgravity attenuates myogenesis and contractile function of 3D engineered skeletal muscle tissues

While the effects of microgravity on inducing skeletal muscle atrophy have been extensively studied, the impacts of microgravity on myogenesis and its mechanisms remain unclear. In this study, we developed a microphysiological system of engineered muscle tissue (EMT) fabricated using a collagen / Matrigel composite hydrogel and murine skeletal myoblasts. This 3D EMT model allows non-invasive quantitative assessment of contractile function. After applying a 7-day differentiation protocol to induce myotube formation, the EMTs clearly exhibited sarcomerogenesis, myofilament formation, and synchronous twitch and tetanic contractions with electrical stimuli. Using this 3D EMT system, we investigated the effects of simulated microgravity at 10−3 G on myogenesis and contractile function utilizing a random positioning machine. EMTs cultured for 5 days in simulated microgravity exhibited significantly reduced contractile forces, myofiber size, and differential expression of muscle contractile, myogenesis regulatory, and mitochondrial biogenesis-related proteins. These results indicate simulated microgravity attenuates myogenesis, resulting in impaired muscle function.

Radiomics and radiogenomics in intrahepatic cholangiocarcinoma

Purpose of the study. Analytical review and analysis of available literature on texture analysis of computed tomgraphy (CT) and magnetic resonance imaging (MRI) in noninvasive diagnosis of ICC and correlation with molecular genetic features and tumor immunophenotype.Materials and methods. The scientific publications and clinical guidelines in the information- analytical systems PubMed, Scopus for 2012–2022 were carried out using the keywords: "mri", "radiomics", "texture analysis", "radiogenomics", "intrahepatic cholangiocarcinoma", "molecular". 49 articles were selected for analysis after excluding studies dealing with technical aspects of radiomics and describing individual clinical observations.Results. The presented review demonstrated the broad possibilities and prospects of application of CT and MRI texture analysis in the study of cholangiocellular cancer, including the first results in the study of molecular features (signatures) of this tumor. Correlation of texture features with the expression of immunotherapy target genes KRAS/NRAS/BRAF as well as IDH1/2 mutation was shown. Texture scores were the predominant independent predictor of microvascular invasion, which was a major independent risk factor for postoperative recurrence.Conclusion. The use of texture analysis undoubtedly demonstrates promising possibilities both in noninvasive assessment of the HCC histological differentiation grade, as well as in differential diagnosis with hepatocellular carcinoma, metastases, and requires further study for systematization and standardization of the obtained data.

Accuracy and temporal analysis of non-Newtonian models of blood in the computational FFR – Numerical implementation

Non-invasive assessment of stenosed coronary is a goal for clinical applications. Thus, engineering aligned with medicine has been the solution to solve this problem. This work, serving as a proof of concept, has the main goal to predict the non-invasive fractional flow reserve (FFR) in an atherosclerotic coronary artery. A 3-element Windkessel and Womersley models were used to model boundary conditions of the patient-specific coronary arteries: the pressure at the outlets of the artery and the velocity at the inlet, respectively. Apart from implementing the previous conditions in the numerical code, the novelty of this work is to implement and use, in numerical simulations, Newtonian and non-Newtonian models for blood such as Carreau, Carreau-Yasuda, Casson and Simplified Phan-Thien/Tanner to analyse the accuracy of the computed FFR and the computational time of the simulations. Results indicate that the non-Newtonian viscoelastic model, Simplified Phan-Thien/Tanner, took the longest time but produced the most accurate results - 8h and 2.7% relative error between invasive and non-invasive FFR. The shear-thinning non-Newtonian models required lower computational times but returned a higher average error (3.9h; 7.6% error) which is considered significant. The Newtonian model required the least time but had the highest error value (2.9h; 7.8% error). Thus, although the computational time considering the non-Newtonian viscoelastic model is the highest, this model must be considered in the numerical simulations to obtain the FFR since it is the most accurate for this patient case. This research is a step forward to numerically quantify the non-invasive FFR of a patient.

Development and validation of a model for predicting the expression of Ki-67 in pancreatic ductal adenocarcinoma with radiological features and dual-energy computed tomography quantitative parameters

ObjectiveTo construct and validate a model based on the dual-energy computed tomography (DECT) quantitative parameters and radiological features to predict Ki-67 expression levels in pancreatic ductal adenocarcinoma (PDAC).Materials and methodsData from 143 PDAC patients were analysed. The variables of clinic, radiology and DECT were evaluated. In the arterial phase and portal venous phase (PVP), the normalized iodine concentration (NIC), normalized effective atomic number and slope of the spectral attenuation curves were measured. The extracellular volume fraction (ECVf) was measured in the equilibrium phase. Univariate analysis was used to screen independent risk factors to predict Ki-67 expression. The Radiology, DECT and DECT–Radiology models were constructed, and their diagnostic effectiveness and clinical applicability were obtained through area under the curve (AUC) and decision curve analysis, respectively. The nomogram was established based on the optimal model, and its goodness-of-fit was assessed by a calibration curve.ResultsComputed tomography reported regional lymph node status, NIC of PVP, and ECVf were independent predictors for Ki-67 expression prediction. The AUCs of the Radiology, DECT, and DECT–Radiology models were 0.705, 0.884, and 0.905, respectively, in the training cohort, and 0.669, 0.835, and 0.865, respectively, in the validation cohort. The DECT–Radiology nomogram was established based on the DECT–Radiology model, which showed the highest net benefit and satisfactory consistency.ConclusionsThe DECT–Radiology model shows favourable predictive efficacy for Ki-67 expression, which may be of value for clinical decision-making in PDAC patients.Critical relevance statementThe DECT–Radiology model could contribute to the preoperative and non-invasive assessment of Ki-67 expression of PDAC, which may help clinicians to screen out PDAC patients with high Ki-67 expression.Key points• Dual-energy computed tomography (DECT) can predict Ki-67 in pancreatic ductal adenocarcinoma (PDAC).• The DECT–Radiology model facilitates preoperative and non-invasive assessment of PDAC Ki-67 expression.• The nomogram may help screen out PDAC patients with high Ki-67 expression.Graphical

STrIP Score for Neonatal Jaundice: From Bench to Bedside

Background: Non-invasive assessment of neonatal hyperbilirubinemia is done clinically with the Kramer scale and transcutaneous bilirubinometer. Recently, the Stool color for Triage of Infants needing Phototherapy (STrIP) score was studied and found to be better than both of the above methods in predicting measured serum bilirubin. This study sheds light on the clinical utility of the STrIP score in making therapeutic decisions. Method: This was a prospective study done in a tertiary-level neonatal unit. Breastfed term babies with clinical jaundice were recruited. The Kramer scale and STrIP score were performed on them and compared with respect to the therapeutic decision of commencing phototherapy based on measured serum bilirubin. Results: One hundred and twenty-eight infants were studied. The Kramer scale correctly aided the therapeutic decision on phototherapy (either to start or not to start) in 47 (36.7%) and the STrIP score in 119 (93%) of our subjects ( p = .0001). In 81 (63.2%) of the subjects, the Kramer scale underestimated the need for phototherapy. In contrast, the STrIP score overestimated the need for phototherapy in 11 (9%). Conclusion: The STrIP score helps in making more accurate therapeutic decisions in neonatal hyperbilirubinemia compared to the Kramer scale alone with respect to commencing phototherapy.

Possible use of 2D shear wave liver elastography in new-onset ascites evaluation

BackgroundNo data on the use of 2D shear wave elastography exists regarding the evaluation of the new-onset ascites causality.AimsTo determine whether 2D shear wave elastography can help in the non-invasive assessment of the new-onset ascites cause. To assess the applicability of liver stiffness measured by 2D shear wave elastography using Esaote MyLab Nine apparatus in patients with ascites.MethodsIn 52 consecutive patients with new-onset ascites (January 2020 to October 2021), liver stiffness using 2D shear wave elastography was prospectively measured. The reliable measurements were used for further analysis. Relevant clinical and laboratory data was collected.ResultsThe calculated liver stiffness measurement cut-off value of 14.4 kPa held 94% accuracy, 100% sensitivity, and 83% specificity when determining ascites with serum ascites albumin gradient ≥11 g/L. Reliable 2D shear wave elastography success rate was 84%.Conclusions2D shear wave elastography may potentially be used to differentiate transudative from exudative ascites, especially in patients with portal hypertension and peritoneal carcinomatosis.

DCS blood flow index underestimates skeletal muscle perfusion in vivo: rationale and early evidence for the NIRS-DCS perfusion index.

Diffuse correlation spectroscopy (DCS) permits non-invasive assessment of skeletal muscle blood flow but may misestimate changes in muscle perfusion. We aimed to highlight recent evidence that DCS blood flow index (BFI) misestimates changes in muscle blood flow during physiological perturbation and to introduce a novel approach that adjusts BFI for estimated changes in vasodilation. We measured changes in muscle BFI during quadriceps and forearm exercises using DCS, the latter of which were adjusted for estimated changes in microvascular flow area and then compared to Doppler ultrasound in the brachial artery. Then, we compared adjusted BFI- and arterial spin labeling (ASL) MRI measures of gastrocnemius blood flow during reactive hyperemia and plantar flexion exercise. We observed little-to-no change in quadriceps BFI during maximal-effort exercise. Similarly, forearm BFI was modestly increased during handgrip exercise, but the magnitude was significantly lower than measured by Doppler ultrasound in the brachial artery. However, this difference was ameliorated after adjusting BFI for estimated changes in microvascular flow area. Similar observations were also observed in the gastrocnemius when directly comparing the adjusted BFI values to ASL-MRI. Adjusting BFI for estimated changes in microvascular flow area may improve DCS estimates of muscle blood flow, but further study is needed to validate these methods moving forward.

Interpretable machine learning model integrating clinical and elastosonographic features to detect renal fibrosis in Asian patients with chronic kidney disease.

Non-invasive renal fibrosis assessment is critical for tailoring personalized decision-making and managing follow-up in patients with chronic kidney disease (CKD). We aimed to exploit machine learning algorithms using clinical and elastosonographic features to distinguish moderate-severe fibrosis from mild fibrosis among CKD patients. A total of 162 patients with CKD who underwent shear wave elastography examinations and renal biopsies at our institution were prospectively enrolled. Four classifiers using machine learning algorithms, including eXtreme Gradient Boosting (XGBoost), Support Vector Machine (SVM), Light Gradient Boosting Machine (LightGBM), and K-Nearest Neighbor (KNN), which integrated elastosonographic features and clinical characteristics, were established to differentiate moderate-severe renal fibrosis from mild forms. The area under the receiver operating characteristic curve (AUC) and average precision were employed to compare the performance of constructed models, and the SHapley Additive exPlanations (SHAP) strategy was used to visualize and interpret the model output. The XGBoost model outperformed the other developed machine learning models, demonstrating optimal diagnostic performance in both the primary (AUC = 0.97, 95% confidence level (CI) 0.94-0.99; average precision = 0.97, 95% CI 0.97-0.98) and five-fold cross-validation (AUC = 0.85, 95% CI 0.73-0.98; average precision = 0.90, 95% CI 0.86-0.93) datasets. The SHAP approach provided visual interpretation for XGBoost, highlighting the features' impact on the diagnostic process, wherein the estimated glomerular filtration rate provided the largest contribution to the model output, followed by the elastic modulus, then renal length, renal resistive index, and hypertension. This study proposed an XGBoost model for distinguishing moderate-severe renal fibrosis from mild forms in CKD patients, which could be used to assist clinicians in decision-making and follow-up strategies. Moreover, the SHAP algorithm makes it feasible to visualize and interpret the feature processing and diagnostic processes of the model output.

Non-invasive hemodynamic assessment in obese pregnant women compared with non-obese patients: A prospective studY

Non-invasive hemodynamic assessment in obese pregnant women compared with non-obese patients: A prospective studY

Hyperspectral imaging for non-invasive blood oxygen saturation assessment

Hyperspectral Imaging (HSI) seamlessly integrates imaging and spectroscopy, capturing both spatial and spectral data concurrently. With widespread applications in medical diagnostics, HSI serves as a noninvasive tool for gaining insights into tissue characteristics. The distinctive spectral profiles of biological tissues set HSI apart from traditional microscopy in enabling in vivo tissue analysis. Despite its potential, existing HSI techniques face challenges such as alignment issues, low light throughput, and tissue heating due to intense illumination. This study introduces an innovative HSI system featuring active sequential bandpass illumination seamlessly integrated into conventional optical instruments. The primary focus is on analyzing oxyhemoglobin and deoxyhemoglobin saturation in animal tissue samples using multivariate linear regression. This approach holds promise for enhancing noninvasive medical diagnostics. A key feature of the system, active bandpass illumination, effectively prevents tissue overheating, thereby bolstering its suitability for medical applications.

RETINAL MICROVASCULAR CHANGES AND RISK OF CORONARY HEART DISEASE: A Systematic Review and Meta-Analysis.

To quantify associations between various retinal microvascular changes and the risk of the development of coronary heart disease (CHD). PubMed, Embase, Web of Science, and Cochrane Library databases were searched for cohort studies on the association between retinal microvascular changes and incident CHD up to July 31, 2023. The summary risk estimates were estimated using the random-effects model. Subgroup and sensitivity analyses were performed to investigate the potential source of heterogeneity. The authors identified 21 studies that met the inclusion criteria of this meta-analysis through database searching. This study yielded significant associations between retinal microvascular changes, including arteriolar narrowing, venular widening, vessel occlusion, and other retinal vascular signs, and the risk of CHD, with pooled adjusted hazard ratios of 1.20 (95% confidence interval: 1.13-1.27). In sex- and age-stratified analyses, retinal microvascular changes were associated with a greater risk of developing CHD in female patients and younger adults. A range of retinal microvascular changes was associated with the risk of CHD, particularly in female patients and younger ages. The results of this study support the concept that retinal microvascular abnormalities may be markers for future CHD. Noninvasive retinal microvascular assessments may be helpful in screening patients with increased CHD risk.

Echocardiographic parameters of cardiac structure and function in the diagnosis of acute myocarditis in adult patients: A systematic review and meta-analysis.

Transthoracic echocardiography (TTE) plays a key role in the initial work-up of myocarditis where the identification of pathologic structural and functional changes may assist in its diagnosis and management. The aim of this systematic review was to appraise the evidence for the utility of echocardiographic parameters of cardiac structure and function in the diagnosis of myocarditis in adult populations. A systematic literature search of medical databases was performed using PRISMA principles to identify all relevant studies assessing TTE parameters in adult patients with myocarditis (1995-2020; English only; PROSPERO registration CRD42021243598). Data for a range of structural and functional TTE parameters were individually extracted and those with low heterogeneity were then meta-analyzed using a random-effects model for effect size, and assessed through standardized mean difference (SMD). Available data from six studies (with a pooled total of 269 myocarditis patients and 240 controls) revealed that myocarditis can be reliably differentiated from healthy controls using echocardiographic measures of left ventricular (LV) size and systolic function, in particular LV end-diastolic diameter, LV ejection fraction (LVEF) and LV global longitudinal strain (LV-GLS) (p ≤ .01 for all). LV-GLS demonstrated the highest overall effect size, followed by LVEF and LVEDD (SMD: |0.46-1.98|). Two studies also demonstrated that impairment in LV-GLS was associated with adverse cardiovascular outcomes in this population, irrespective of LVEF. LV-GLS demonstrated the greatest overall effect size and therefore ability to differentiate myocarditis populations from healthy controls. GLS was also shown to be a predictor of adverse cardiovascular outcomes, in this population. What is already known on this subject? Myocarditis is a disease process that is often a diagnosis of exclusion, as it frequently mimics other acute cardiac pathologies. Transthoracic echocardiography is traditionally the initial imaging modality used for noninvasive structural assessment in populations with myocarditis. What might this study add? This study demonstrates that left ventricular (LV) global longitudinal strain, LV ejection fraction and LV end-diastolic diameter can differentiate between myocarditis patients and healthy controls. LV-GLS demonstrated the greatest overall effect size when comparing these two populations, in comparison to the other measures. How might this impact on clinical practice? This study demonstrates that assessment of myocardial deformation indices allows for sensitive discrimination between myocarditis patients from healthy controls. Routine assessment of LV-GLS may serve as an important diagnostic tool in the acute care setting.

Non-invasive assessment of hepatic steatosis by ultrasound-derived fat fraction (UDFF) in individuals at high-risk for metabolic dysfunction-associated steatotic liver disease

Non-invasive assessment of hepatic steatosis by ultrasound-derived fat fraction (UDFF) in individuals at high-risk for metabolic dysfunction-associated steatotic liver disease

Utilization of the corticomedullary difference in magnetic resonance imaging-derived apparent diffusion coefficient for noninvasive assessment of chronic kidney disease in type 2 diabetes

BackgroundsAccumulating data demonstrated that the cortico-medullary difference in apparent diffusion coefficient (ΔADC) of diffusion-weighted magnetic resonance imaging (DWI) was a better correlation with kidney fibrosis, tubular atrophy progression, and a predictor of kidney function evolution in chronic kidney disease (CKD). ObjectivesWe aimed to assess the value of ΔADC in evaluating disease severity, differential diagnosis, and the prognostic risk stratification for patients with type 2 diabetes (T2D) and CKD. MethodsTotal 119 patients with T2D and CKD who underwent renal MRI were prospectively enrolled. Of them, 89 patients had performed kidney biopsy for pathological examination, including 38 patients with biopsy-proven diabetic kidney disease (DKD) and 51 patients with biopsy-proven non-diabetic kidney disease (NDKD) and Mix (DKD + NDKD). Clinicopathological characteristics were compared according to different ΔADC levels. Moreover, univariate and multivariate-linear regression analyses were performed to explore whether ΔADC was independently associated with estimated glomerular filtration rate (eGFR) and urinary albumin creatinine ratio (UACR). The diagnostic performance of ΔADC for discriminating DKD from NDKD + Mix was evaluated by receiver operating characteristic (ROC) analysis. In addition, an individual's 2- or 5-year risk probability of progressing to end-stage kidney disease (ESKD) was calculated by the kidney failure risk equation (KFRE). The effect of ΔADC on prognostic risk stratification was assessed. Additionally, net reclassification improvement (NRI) was used to evaluate the model performance. ResultsAll enrolled patients had a median ΔADC level of 86 (IQR 28, 155) × 10−6 mm2/s. ΔADC significantly decreased across the increasing staging of CKD (P < 0.001). Moreover, those with pathological-confirmed DKD has a significantly lower level of ΔADC than those with NDKD and Mix (P < 0.001). It showed that ΔADC was independently associated with eGFR (β = 1.058, 95% CI = [1.002,1.118], P = 0.042) and UACR (β = −3.862, 95% CI = [-7.360, -0.365], P = 0.031) at multivariate linear regression analyses. Besides, ΔADC achieved an AUC of 0.707 (71% sensitivity and 75% specificity) and AUC of 0.823 (94% sensitivity and 67% specificity) for discriminating DKD from NDKD + Mix and higher ESKD risk categories (≥50% at 5 years; ≥10% at 2 years) from lower risk categories (<50% at 5 years; <10% at 2 years). Accordingly, the optimal cutoff value of ΔADC for higher ESKD risk categories was 66 × 10−6 mm2/s, and the group with the low-cutoff level of ΔADC group was associated with 1.232 -fold (95% CI 1.086, 1.398) likelihood of higher ESKD risk categories as compared to the high-cutoff level of ΔADC group in the fully-adjusted model. Reclassification analyses confirmed that the final adjusted model improved NRI. ConclusionsΔADC was strongly associated with eGFR and UACR in patients with T2D and CKD. More importantly, baseline ΔADC was predictive of higher ESKD risk, independently of significant clinical confounding. Specifically, ΔADC <78 × 10−6 mm2/s and <66 × 10−6 mm2/s would help to identify T2D patients with the diagnosis of DKD and higher ESKD risk categories, respectively.

Point-of-care device for the noninvasive assessment of hepatic macrosteatosis in liver donors

BackgroundQuantification of macrosteatosis (MS) in the liver is important given that it has shown to directly correlate with adverse post-liver transplant (LT) outcomes. With advances in medical technology and an implicit understanding of pathology, noninvasive methods of quantitatively assessing MS are in various stages of development. Each of these methods is based on the physical principles of differences between a fat-laden hepatocyte and a normal one. MethodsIn this regard, after a proof-of-concept study on a prototype for a simple, real-time, handheld device using the principle of diffuse reflectance spectroscopy, this study presents an upgraded point-of-care (POC) device for the noninvasive assessment of hepatic MS in liver donors. ResultsThe device was validated on cohort of donor livers and showed a sensitivity (0.0021 V/% fat) and highly correlated (r = 0.9868, P < .0001) with gold-standard liver biopsy. Results showed that this upgraded POC device provides a reliable method for the noninvasive assessment of hepatic MS, which is crucial for selecting suitable donor livers for LT. ConclusionThe device has the potential to be an invaluable apparatus at the hands of the organ-retrieving surgeon. It is noninvasive, portable (handheld), and economic; provides real-time readings of the percentage of MS; and can be efficaciously handled by any member of the organ-retrieving team.

Intestinal barrier biomarkers in clinical evaluation of patients with inflammatory bowel disease.

Inflammatory bowel disease (IBD) is associated with chronic intestinal barrier dysfunction, though its non-invasive assessment remains challenging. This study aimed to determine how four putative circulating markers vary across differing states of intestinal inflammation and with therapy in patients with IBD. Plasma samples from one prospective cross-sectional and four longitudinal studies, including healthy controls, were analysed for markers of lipopolysaccharide translocation, lipopolysaccharide-binding protein (LBP) and soluble-CD14 (sCD14), and markers of epithelial injury, syndecan-1 and intestinal-type fatty acid-binding protein (IFABP). Inflammatory activity was determined using objective measures. Compared with healthy subjects, concentrations of LBP and sCD14 were higher in patients with active (P < 0.001) and severe ulcerative colitis (UC) (P < 0.0001) and active Crohn's disease (CD) (P < 0.001). In UC in remission, LBP was less than in active disease (P = 0.011) LBP levels decreased longitudinally before and after induction of medical therapy in patients with IBD (P = 0.030) and as severe UC was brought into remission at weeks 2 and 12 (P ≤ 0.022). Response to treatment was associated with higher baseline levels of LBP (P = 0.019) and soluble-CD14 (P = 0.014). Concentrations of syndecan-1 and IFABP were or tended to be lower in UC and CD in active disease and did not change with successful therapy. While markers of epithelial injury were subnormal with active disease and did not change with therapy, markers of lipopolysaccharide translocation directly reflected intestinal inflammation, reduced with successful therapy and predicted treatment response.

MRI-derived radiomics assessing tumor-infiltrating macrophages enable prediction of immune-phenotype, immunotherapy response and survival in glioma

BackgroundThe tumor immune microenvironment can influence the prognosis and treatment response to immunotherapy. We aimed to develop a non-invasive radiomic signature in high-grade glioma (HGG) to predict the absolute density of tumor-associated macrophages (TAMs), the preponderant immune cells in the microenvironment of HGG. We also aimed to evaluate the association between the signature, and tumor immune phenotype as well as response to immunotherapy.MethodsIn this retrospective setting, total of 379 patients with HGG from three independent cohorts were included to construct a radiomic model named Radiomics Immunological Biomarker (RIB) for predicting the absolute density of M2-like TAM using the mRMR feature ranking method and LASSO classifier. Among them, 145 patients from the TCGA microarray cohort were randomly allocated into a training set (N=101) and an internal validation set (N=44), while the immune-phenotype cohort (N=203) and the immunotherapy-treated cohort (N=31, patients from a prospective clinical trial treated with DC vaccine) recruited from Huashan Hospital were used as two external validation sets. The immunotherapy-treated cohort was also used to evaluate the relationship between RIB and immunotherapy response. Radiogenomic analysis was performed to find functional annotations using RNA sequencing data from TAM cells.ResultsAn 11-feature radiomic model for M2-like TAM was developed and validated in four datasets of HGG patients (area under the curve = 0.849, 0.719, 0.674, and 0.671) using MRI images of post contrast enhanced T1-weighted (T1CE). Patients with high RIB scores had a strong inflammatory response. Four hub-genes (SLC7A7, RNASE6, HLA-DRB1 and CD300A) expressed by TAM were identified to be closely related to the RIB, providing important evidence for biological interpretation. Only individuals with a high RIB score were shown to have survival benefits from DC vaccine [DC vaccine vs. Placebo: median progression-free survival (mPFS), 10.0 mos vs. 4.5 mos, HR=0.17, P=0.0056, 95%CI=0.041-0.68; median overall survival (mOS), 15.0 mos vs. 7.0 mos, HR=0.17, P =0.0076, 95%CI=0.04-0.68]. Multivariate analyses also confirmed that treatment by DC vaccine was an independent factor for improved survival in the high RIB score group. However, in the low RIB score group, DC vaccine was not associated with improved survival. Furthermore, a radiomic nomogram based on the RIB score and clinical factors could efficiently predict the 1-, 2-, and 3-year survival rates, as confirmed by ROC curve analysis (AUC for 1-, 2- and 3-year survival: 0.705, 0.729 and 0.684, respectively).ConclusionsThe radiomic model could allow for non-invasive assessment of the absolute density of TAM from MRI images in HGG patients. Of note, our RIB model is the first immunological radiomic model confirmed to have the ability to predict survival benefits from DC vaccine in gliomas, thereby providing a novel tool to inform treatment decisions and monitor patient treatment course by radiomics.