Noninvasive Imaging Research Articles

Resolve and dissolve-An ultrasound-guided investigation on the effects of hyaluronidase on different soft tissue fillers.

Nonsurgical cosmetic procedures, particularly the use of hyaluronic acid (HA)-based soft tissue fillers, are becoming increasingly popular. This trend has catalyzed the development of a plethora of HA-based products differing in product characteristics, thereby catering to an ever-widening spectrum of aesthetic applications. However, complications rise concomitant with the increasing number of procedures. Among the strategies to manage such adverse events is the enzymatic breakdown with hyaluronidase. To analyze the response of different HA-based soft tissue filler materials to hyaluronidase injections. A total of 11 different HA-based soft tissue fillers were evaluated using noninvasive ultrasound imaging to assess their behavior in response to hyaluronidase injections. The HA-based soft tissue fillers were categorized according to their product characteristics into a structuring, volumizing, and lip volumizing group. Standardized injections of 0.2 cc were performed in chicken breast to simulate human tissue. Ultrasound measurements of width, height, and calculated volume were performed immediately after filler injection, 1 h and 24 h following hyaluronidase injection. Regardless of the soft tissue filler analyzed, the most significant volume reduction occurred within the first h after applying hyaluronidase, with a 64.1% decrease from the initial volume. After 24 h, the total volume reduction reached 81.7%. No statistically significant differences were found when comparing the three groups at each follow-up time period, except for the height measurement after 1 h. While width was statistically significant in all groups between the investigated follow-up groups, the volume reduction was only statistically significant in the groups with the highest and second highest G' values (i.e., Group 1-structuring, Group 2-volumizing). The effectiveness of hyaluronidase in dissolving HA-based fillers is initially independent of product characteristics of HA-based fillers such as G-prime, with increased efficacy in fillers with higher G-prime values, as evidenced by significant volume reductions in such groups.

Radiomics to Detect Inflammation and Fibrosis on Magnetic Resonance Enterography in Stricturing Crohn's Disease.

Non-invasive cross-sectional imaging via magnetic resonance enterography (MRE) offers excellent accuracy for the diagnosis of stricturing complications in Crohn's disease (CD) but is limited in determining the degrees of fibrosis and inflammation within a stricture. We developed and validated a radiomics-based machine-learning model for separately characterizing the degree of histopathologic inflammation and fibrosis in CD strictures and compared it to centrally read visual radiologist scoring of MRE. This single center, cross-sectional study, included 51 CD patients (n=34 for discovery; n=17 for validation) with terminal ileal strictures confirmed on diagnostic MRE within 15 weeks of resection. Histopathological specimens were scored for inflammation and fibrosis and spatially linked with corresponding pre-surgical MRE sequences. Annotated stricture regions on MRE were scored visually by radiologists as well as underwent 3D radiomics-based machine learning analysis; both evaluated against histopathology. Two distinct sets of radiomic features capturing textural heterogeneity within strictures were linked with each of severe inflammation or severe fibrosis across both discovery (area under the curve (AUC)=0.69, 0.83) and validation (AUCs=0.67,0.78) cohorts. Radiologist visual scoring had an AUC=0.67 for identifying severe inflammation and AUC=0.35 for severe fibrosis. Use of combined radiomics and radiologist scoring robustly augmented identification of severe inflammation (AUC=0.79) and modestly improved assessment of severe fibrosis (AUC=0.79 for severe fibrosis) over individual approaches. Radiomic features of CD strictures on MRE can accurately identify severe histopathologic inflammation and severe histopathologic fibrosis, as well as augment performance of radiologist visual scoring in stricture characterization.

Noninvasive Fluorescence Imaging Through Scattering Media Beyond Memory Effect via Speckle Correlations

AbstractThe memory‐effect‐based speckle auto‐correlation method has gained significant attention for its ability to perform single‐shot noninvasive imaging through scattering media. Despite its advantages, however, not only its imaging field‐of‐view (FOV) is limited by the memory effect (ME), but also the relative positions and orientations of the reconstructed objects beyond ME are lost. Therefore, an approach that enables the reconstruction of multiple objects or a whole object behind scattering media beyond the ME region while accurately preserving the relative positions and orientations of its sub‐objects is proposed. The method achieves this by directly leveraging the correlation of the collected speckle patterns. Experimental results validate the effectiveness of the proposed method. It not only can reconstruct the image of multiple objects or a whole object beyond the ME region simulated by a digital micromirror device but also can reconstruct the image of a fluorescent object beyond the ME region noninvasively, which is well consistent with the theoretical predictions. The method provides a promising pathway for noninvasively visualizing fluorescent objects behind scattering media without being constrained by ME, thereby expanding the imaging FOV.

Non-invasive electrical brain stimulation modulates human conscious perception of mental representation

Mental representation is a key concept in cognitive science; nevertheless, its neural foundations remain elusive. We employed non-invasive electrical brain stimulation and functional magnetic resonance imaging to address this. During this process, participants perceived flickering red and green visual stimuli, discerning them either as distinct, non-fused colours or as a mentally generated, fused colour (orange). The application of transcranial alternating current stimulation to the medial prefrontal region (a key node of the default-mode network) suppressed haemodynamic activation in higher-order subthalamic and central executive networks associated with the perception of fused colours. This implies that higher-order thalamocortical and default-mode networks are crucial in humans’ conscious perception of mental representation.

Near-Infrared-II Imaging Revealed Hypothermia Regulates Neuroinflammation Following Brain Injury by Increasing the Glymphatic Influx.

Advanced in vivo imaging techniques have facilitated the comprehensive visual exploration of animal biological processes, leading to groundbreaking discoveries such as the glymphatic system. However, current limitations of macroscopic imaging techniques impede the precise investigation of physiological parameters regulating this specialized lymphatic transport system. While NIR-II fluorescence imaging has demonstrated advantages in peripheral lymphatic imaging, there are few reports regarding its utilization in the glymphatic system. To address this, a noninvasive transcranial macroscopic NIR-II fluorescence imaging model is developed using a cyanine dye-protein coupled nanoprobe. NIR-II imaging with high temporal and spatial resolution reveals that hypothermia can increase the glymphatic influx by reducing the flow rate of cerebrospinal fluid. In addition, respiratory rate, respiratory amplitude, and heart rate all play a role in regulating the glymphatic influx. Thus, targeting the glymphatic influx may alter the trajectory of immune inflammation following brain injury, providing therapeutic prospects for treating brain injury with mild hypothermia.

Granzyme B PET Imaging for Assessment of Disease Activity in Inflammatory Bowel Disease.

Developing a noninvasive imaging method to detect immune system activation with a high temporal resolution is key to improving inflammatory bowel disease (IBD) management. In this study, granzyme B (GZMB), typically released from cytotoxic T and natural killer cells, was targeted using PET with 68Ga-NOTA-GZP (where GZP is β-Ala-Gly-Gly-Ile-Glu-Phe-Asp-CHO) to detect early intestinal inflammation in murine models of colitis. Methods: Bioinformatic analysis was used to assess the potential of GZMB as a biomarker for detecting IBD and predicting response to treatment. Human active and quiescent Crohn disease and ulcerative colitis tissues were stained for GZMB. We used IL-10-/- mice treated with dextran sulfate sodium (DSS) as an IBD model, wild-type C57BL/6J mice as a control, and anti-tumor necrosis factor as therapy. We used a murine GZMB-binding peptide conjugated to a NOTA chelator (NOTA-GZP) labeled with 68Ga as the PET tracer. PET imaging was conducted at 1, 3, and 4 wk after colitis induction to evaluate temporal changes. Results: Bioinformatic analysis showed that GZMB gene expression is significantly upregulated in human ulcerative colitis and Crohn disease compared with the noninflamed bowel by 2.98-fold and 1.92-fold, respectively; its expression is lower by 2.16-fold in treatment responders than in nonresponders. Immunofluorescence staining of human tissues demonstrated a significantly higher GZMB in patients with active than with quiescent IBD (P = 0.032).68Ga-NOTA-GZP PET imaging showed significantly increased bowel uptake in IL-10-/- mice with DSS-induced colitis compared with vehicle-treated IL-10-/- mice (SUVmean, 0.75 vs. 0.24; P < 0.001) and both vehicle- and DSS-treated wild-type mice (SUVmean, 0.26 and 0.37; P < 0.001). In the IL-10-/- DSS-induced colitis model, the bowel PET probe uptake decreased in response to treatment with tumor necrosis factor-α (SUVmean, 0.32; P < 0.001). There was a 4-fold increase in colonic uptake of 68Ga-NOTA-GZP in the colitis model compared with the control 1 wk after colitis induction. The uptake gradually decreased to approximately 2-fold by 4 wk after IBD induction; however, the inflamed bowel uptake remained significantly higher than control at all time points (week 4 SUVmean, 0.23 vs. 0.08; P = 0.001). Conclusion: GZMB is a promising biomarker to detect active IBD and predict response to treatment. This study provides compelling evidence to translate GZMB PET for imaging IBD activity in clinical settings.

Potential Efficacy of 68Ga-Trivehexin PET/CT and Immunohistochemical Validation of αvβ6 Integrin Expression in Patients With Head and Neck Squamous Cell Carcinoma and Pancreatic Ductal Adenocarcinoma.

αvβ6 integrin is exclusively expressed in epithelial cells and is upregulated in many carcinomas, such as pancreatic ductal adenocarcinomas (PDACs) and head and neck squamous cell carcinomas (H&NSCCs). Trivehexin is a recently synthesized trimerized αvβ6 integrin selective nonapeptide, which can be labeled with a positron emitter like 68Ga. This is a pilot study to assess the potential role of 68Ga-Trivehexin PET/CT in patients with H&NSCC and PDAC and their correlation with αvβ6 integrin expression by the tumor tissue on immunohistochemistry (IHC). Thirty-two patients with suspected H&NSCC (n = 20) or PDAC (n = 12) underwent whole-body 68Ga-Trivehexin PET/CT and 18F-FDG PET/CT scans on 2 separate days. All 32 patients underwent biopsy from the tumor site for histopathological diagnosis and IHC for αvβ6 integrin expression. The degree of αvβ6 integrin expression on IHC was scored using the immunoreactive score and modified 4-point immunoreactive score classification. The 68Ga-Trivehexin PET images demonstrated increased tracer uptake (mean SUVmax 5.9 ± 3.3) in the primary and metastatic lesions with good lesion delineation in 8 out of the 9 cases of PDACs. However, FDG PET showed increased tracer uptake in 7 cases (6.2 ± 2.6). Among various cases of H&NSCC, increased uptakes of 68Ga-Trivehexin (6.6 ± 4.5) and 18F-FDG (12.7 ± 6.7) were seen in 17 out of the 18 patients. The 2 cases of inflammatory changes with suspected disease recurrence showed increased tracer uptake in 18F-FDG PET (7.98 ± 3.1) and no significant uptake in 68Ga-Trivehexin PET (2.2 ± 0.34).IHC showed higher expression of αvβ6 integrins in lesions with higher uptake of 68Ga-Trivehexin. A higher sensitivity, specificity, and accuracy of 68Ga-Trivehexin PET over 18F-FDG PET was seen for detection of primary and metastatic lesions. 68Ga-Trivehexin is a promising noninvasive molecular imaging agent for tumors expressing αvβ6 integrin, especially in cases where 18F-FDG PET/CT scan may be suboptimal due to its low uptake, or due to its nonspecific uptake around tumor sites.

[68Ga]Ga-NODAGA-TriGalactan, a low molecular weight tracer for the non-invasive imaging of the functional liver reserve

BackgroundDetermination of the functional liver mass is important in a variety of clinical settings including liver surgery and transplantation. [99mTc]Tc-diethylenetriamine-pentaacetic acid galactosyl human serum albumin (99mTc-GSA) is a radiotracer targeting the asialoglycoprotein receptor (ASGR) and is routinely used in Japan for this purpose. Here we describe the development and evaluation of [68Ga]Ga-NODAGA-TriGalactan a low molecular weight PET-tracer targeting this structure.ResultsFor synthesis TRIS as branching unit and NODAGA as chelator for labelling with [68Ga]Ga are included. Three galactose moieties are conjugated via a click chemistry approach resulting in the desired labelling precursor.68Ga-labelling could be accomplished in high radiochemical yield and purity. [68Ga]Ga-NODAGA-TriGalactan is very hydrophilic and revealed high plasma stability and low plasma protein binding. Fluorescence imaging showed binding on ASGR-positive organoids and the IC50-value was in the nanomolar range. Most importantly, both biodistribution as well as animal imaging studies using normal mice demonstrated high liver uptake with rapid elimination from all other organs leading to even higher liver-to-background ratios as found for 99mTc-GSA.Conclusion[68Ga]Ga-NODAGA-TriGalactan shows high in vitro stability and selectively binds to the ASGR allowing imaging of the functional liver mass with high contrast. Thus, our first generation compound resulted already in an alternative to 99mTc-GSA for imaging the functional liver reserve and might allow the broader use of this imaging technique.

A comprehensive review on role of magnetic resonance imaging in the precise measurement of corpus callosum

Magnetic Resonance Imaging (MRI) has emerged as a powerful and non-invasive imaging technique, playing a pivotal role in neuroimaging research and clinical diagnosis. This comprehensive review explores the significance of MRI in the precise measurement of the corpus callosum, a key structure connecting the two hemispheres of the brain. The corpus callosum plays a crucial role in inter hemispheric communication and is implicated in various neurological and psychiatric disorders. The review begins by elucidating the anatomy and functions of the corpus callosum, emphasizing its importance in facilitating seamless communication between the cerebral hemispheres. Subsequently, the paper delves into the historical evolution of MRI techniques and how advancements have enhanced the visualization and measurement capabilities of the corpus callosum. A detailed examination of various MRI modalities, including structural MRI, diffusion tensor imaging (DTI), and functional MRI, is presented in the context of corpus callosum analysis. Structural MRI provides high-resolution images for accurate morphological assessments, while DTI offers insights into white matter microstructure and fiber tractography, allowing for a more comprehensive understanding of the corpus callosum's integrity. The review also highlights the role of MRI in investigating alterations in the corpus callosum associated with neurological disorders such as multiple sclerosis, epilepsy, and neurodevelopmental disorders. Additionally, the paper explores how functional MRI contributes to understanding the functional connectivity and inter hemispheric interactions mediated by the corpus callosum. Challenges and limitations in the measurement of the corpus callosum using MRI are discussed, including methodological considerations, image artifacts, and potential sources of variability. The review concludes by outlining future directions in corpus callosum imaging research, including the integration of advanced imaging techniques, artificial intelligence, and large-scale multi-center studies to enhance the precision and reliability of measurements.In summary, this comprehensive review underscores the pivotal role of MRI in advancing our understanding of the corpus callosum, providing valuable insights into both normal brain function and pathological conditions. The continual evolution of MRI techniques holds promise for further refining the assessment of the corpus callosum, ultimately contributing to improved diagnostic accuracy and therapeutic interventions in neurological and psychiatric disorders.

Role of MRI in Evaluation of Post-Traumatic Knee Injuries: A Prospective Study

INTRODUCTIONThe knee joint is the largest and most complex joint in the human body. Therefore it is often affected by trauma. Magnetic Resonance Imaging (MRI) is a non-invasive imaging modality that provides detailed images of the soft tissue structures of the knee joint. The objective of this study was to evaluate MRI findings in patients with post-traumatic knee joint injuries. MATERIAL AND METHODSThis prospective study was carried out using a 3.0 Tesla MRI (Magnetom Lumina) scanner in the Department of Radiodiagno- sis and Medical Imaging at Universal College of Medical Sciences &amp; Teaching Hospital, Bhairahawa, Nepal, involving 128 patients with knee injuries, from September 2023 to February 2024. Data were analyzed using SPSS version 20. RESULTSIn this study of 128 participants, 57.81% were male and 42.19% were female, with a mean age of 38.60±13.05 years. The majority of MRI findings were medial meniscus tear (51.56%), followed by anterior cruciate ligament tear (46.09%), medial collateral ligament sprain (44.53%), lateral meniscus tear (39.84%), lateral collateral ligament sprain (33.59%), and posterior cruciate ligament tear (17.97%). Our study also revealed various grades of collateral ligament injuries, including the medial and lateral ligaments. There were 59.65% of cases with a grade I medial collateral ligament sprain, followed by grade II at 33.33% and grade III at 7.02%. The grade I and grade II lateral collateral ligament sprains were 62.79% and 37.21%, respectively. CONCLUSIONMRI is a non-invasive and valuable diagnostic modality that can provide an accurate diagnosis. It is often preferred over arthroscopy.

MASLD and MASH at the crossroads of hepatology trials and cardiorenal metabolic trials.

Steatotic liver disease (SLD) is a worldwide public health problem, causing considerable morbidity and mortality. Patients with SLD are at increased risk for major adverse cardiovascular (CV) events, type 2 diabetes mellitus and chronic kidney disease. Conversely, patients with cardiometabolic conditions have a high prevalence of SLD. In addition to epidemiological evidence linking many of these conditions, there is evidence of shared pathophysiological processes. In December 2022, a unique multi-stakeholder, multi-specialty meeting, called MOSAIC (Metabolic multi Organ Science Accelerating Innovation in Clinical Trials) was convened to foster collaboration across metabolic, hepatology, nephrology and CV disorders. One of the goals of the meeting was to consider approaches to drug development that would speed regulatory approval of treatments for multiple disorders by combining liver and cardiorenal endpoints within a single study. Non-invasive tests, including biomarkers and imaging, are needed in hepatic and cardiorenal trials. They can be used as trial endpoints, to enrich trial populations, to diagnose and risk stratify patients and to assess treatment efficacy and safety. Although they are used in proof of concept and phase 2 trials, they are often not acceptable for regulatory approval of therapies. The challenge is defining the optimal combination of biomarkers, imaging and morbidity/mortality outcomes and ensuring that they are included in future trials while minimizing the burden on patients, trialists and trial sponsors. This paper provides an overview of some of the wide array of CV, liver and kidney measurements that were discussed at the MOSAIC meeting.

Advances in Non-Invasive Molecular Imaging Probes for Liver Fibrosis Diagnosis

Advances in Non-Invasive Molecular Imaging Probes for Liver Fibrosis Diagnosis

Immunoglobulin G4 disease-related retroperitoneal fibrosis: A series of five cases

Immunoglobulin G4 (IgG4)-related disease has the potential to impact any part of the body, including the walls of large- and medium-sized blood vessels and the ureters. While histopathologic examination is currently the standard method for identifying organ involvement and diagnosing IgG4-related disease (IgG4-RD), obtaining biopsy or surgical samples from vessel or ureteral walls is challenging. Given that patients may display only mild symptoms, non-invasive imaging plays a vital role in both diagnosing and managing IgG4-related diseases. Multidetector CT scans are valuable in establishing the primary diagnosis, identifying anatomical landmarks and assessing their relationships. Involvement of the genitourinary organs, such as the ureter, bladder, urethra, and male and female reproductive organs in IgG4-RD, is infrequent when compared to kidney involvement. The imaging findings may include the presence of a localised mass within or surrounding the affected organ or a generalised enlargement of the organ. This report includes cross-sectional images of five cases of IgG4-RD involving large- and medium-sized blood vessels (the aorta and superior mesenteric artery) and the ureters.Contribution: This case series provides insight into the various imaging appearances of IgG4-related retroperitoneal organ involvement and helps differentiate it radiologically from retroperitoneal fibrosis.

Assessment of tumor hypoxia in spontaneous canine tumors after treatment with OMX, a novel H-NOX oxygen carrier, with [18F]FMISO PET/CT

BackgroundHypoxia is a detrimental factor in solid tumors, leading to aggressiveness and therapy resistance. OMX, a tunable oxygen carrier from the heme nitric oxide/oxygen-binding (H-NOX) protein family, has the potential to reduce tumor hypoxia. [18F]Fluoromisonidazole ([18F]FMISO) positron emission tomography (PET) is the most widely used and investigated method for non-invasive imaging of tumor hypoxia. In this study, we used [18F]FMISO PET/CT (computed tomography) to assess the effect of OMX on tumor hypoxia in spontaneous canine tumors.ResultsThirteen canine patients with various tumors (n = 14) were randomly divided into blocks of two, with the treatment groups alternating between receiving intratumoral (IT) OMX injection (OMX IT group) and intravenous (IV) OMX injection (OMX IV group). Tumors were regarded as hypoxic if maximum tumor-to-muscle ratio (TMRmax) was greater than 1.4. In addition, hypoxic volume (HV) was defined as the region with tumor-to-muscle ratio greater than 1.4 on [18F]FMISO PET images. Hypoxia was detected in 6/7 tumors in the OMX IT group and 5/7 tumors in the OMX IV injection group. Although there was no significant difference in baseline hypoxia between the OMX IT and IV groups, the two groups showed different responses to OMX. In the OMX IV group, hypoxic tumors (n = 5) exhibited significant reductions in tumor hypoxia, as indicated by decreased TMRmax and HV in [18F]FMISO PET imaging after treatment. In contrast, hypoxic tumors in the OMX IT group (n = 6) displayed a significant increase in [18F]FMISO uptake and variable changes in TMRmax and HV.Conclusions[18F]FMISO PET/CT imaging presents a promising non-invasive procedure for monitoring tumor hypoxia and assessing the efficacy of hypoxia-modulating therapies in canine patients. OMX has shown promising outcomes in reducing tumor hypoxia, especially when administered intravenously, as evident from reductions in both TMRmax and HV in [18F]FMISO PET imaging.

Parameter subset reduction for imaging-based digital twin generation of patients with left ventricular mechanical discoordination

BackgroundIntegration of a patient’s non-invasive imaging data in a digital twin (DT) of the heart can provide valuable insight into the myocardial disease substrates underlying left ventricular (LV) mechanical discoordination. However, when generating a DT, model parameters should be identifiable to obtain robust parameter estimations. In this study, we used the CircAdapt model of the human heart and circulation to find a subset of parameters which were identifiable from LV cavity volume and regional strain measurements of patients with different substrates of left bundle branch block (LBBB) and myocardial infarction (MI). To this end, we included seven patients with heart failure with reduced ejection fraction (HFrEF) and LBBB (study ID: 2018-0863, registration date: 2019–10–07), of which four were non-ischemic (LBBB-only) and three had previous MI (LBBB-MI), and six narrow QRS patients with MI (MI-only) (study ID: NL45241.041.13, registration date: 2013–11–12). Morris screening method (MSM) was applied first to find parameters which were important for LV volume, regional strain, and strain rate indices. Second, this parameter subset was iteratively reduced based on parameter identifiability and reproducibility. Parameter identifiability was based on the diaphony calculated from quasi-Monte Carlo simulations and reproducibility was based on the intraclass correlation coefficient (ICC\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${ICC}$$\\end{document}) obtained from repeated parameter estimation using dynamic multi-swarm particle swarm optimization. Goodness-of-fit was defined as the mean squared error (χ2\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${{{\\chi}}}^{{2}}$$\\end{document}) of LV myocardial strain, strain rate, and cavity volume.ResultsA subset of 270 parameters remained after MSM which produced high-quality DTs of all patients (χ2\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${{{\\chi}}}^{{2}}$$\\end{document} < 1.6), but minimum parameter reproducibility was poor (ICCmin\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${{ICC}}_{{min}}$$\\end{document} = 0.01). Iterative reduction yielded a reproducible (ICCmin\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${{ICC}}_{{min}}$$\\end{document} = 0.83) subset of 75 parameters, including cardiac output, global LV activation duration, regional mechanical activation delay, and regional LV myocardial constitutive properties. This reduced subset produced patient-resembling DTs (χ2\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${{{\\chi}}}^{{2}}$$\\end{document} < 2.2), while septal-to-lateral wall workload imbalance was higher for the LBBB-only DTs than for the MI-only DTs (p < 0.05).ConclusionsBy applying sensitivity and identifiability analysis, we successfully determined a parameter subset of the CircAdapt model which can be used to generate imaging-based DTs of patients with LV mechanical discoordination. Parameters were reproducibly estimated using particle swarm optimization, and derived LV myocardial work distribution was representative for the patient’s underlying disease substrate. This DT technology enables patient-specific substrate characterization and can potentially be used to support clinical decision making.

Noninvasive Atherosclerotic Phenotyping: The Next Frontier into Understanding the Pathobiology of Coronary Artery Disease.

Despite recent advances, coronary artery disease remains one of the leading causes of mortality worldwide. Noninvasive imaging allows atherosclerotic phenotyping by measurement of plaque burden, morphology, activity and inflammation, which has the potential to refine patient risk stratification and guide personalized therapy. This review describes the current and emerging roles of advanced noninvasive cardiovascular imaging methods for the assessment of coronary artery disease. Cardiac computed tomography enables comprehensive, noninvasive imaging of the coronary vasculature, and is used to assess luminal stenoses, coronary calcifications, and distinct adverse plaque characteristics, helping to identify patients prone to future events. Novel software tools, implementing artificial intelligence solutions, can automatically quantify and characterize atherosclerotic plaque from standard computed tomography datasets. These quantitative imaging biomarkers have been shown to improve patient risk stratification beyond clinical risk scores and current clinical interpretation of cardiac computed tomography. In addition, noninvasive molecular imaging in higher risk patients can be used to assess plaque activity and plaque thrombosis. Noninvasive imaging allows unique insight into the burden, morphology and activity of atherosclerotic coronary plaques. Such phenotyping of atherosclerosis can potentially improve individual patient risk prediction, and in the near future has the potential for clinical implementation.

Fusion of full-field optical angiography images via gradient feature detection

Full-field optical angiography (FFOA)—a real-time non-invasive imaging technique for extracting biological blood microcirculation information—contributes to an in-depth understanding of the functional and pathological changes of biological tissues. However, owing to the limitation of the depth-of-field (DOF) of optical lenses, existing FFOA imaging methods cannot capture an image containing every blood-flow information. To address this problem, this study develops a long-DOF full-field optical angiography imaging system and proposes a novel multi-focus image fusion scheme to expand the DOF. First, FFOA images with different focal lengths are acquired by the absorption intensity fluctuation modulation effect. Second, an image fusion scheme based on gradient feature detection in a nonsubsampled contourlet transform domain is developed to capture focus features from FFOA images and synthesize an all-focused image. Specifically, FFOA images are decomposed by NSCT into coefficients and low-frequency difference images; thereafter, two gradient feature detection-based fusion rules are used to select the pre-fused coefficients. The experimental results of both phantom and animal cases show that the proposed fusion method can effectively extend the DOF and address practical FFOA image defocusing problems. The fused FFOA image can provide a more comprehensive description of blood information than a single FFOA image.

Current challenges in imaging the mechanical properties of tissue engineered grafts

The mechanical performance of tissue-engineered grafts is crucial in determining their functional properties, integration with native tissue and long-term repair outcome post-implantation. To date, most approaches for testing the mechanical properties of tissue-engineered grafts are non-sterile and invasive. There is an urgent need to develop novel sterile approaches for online monitoring mechanical properties of engineered tissues in order to ensure these engineered products meet the desired mechanical strength prior to implantation. In this paper, we overview various approaches for mechanical testing of engineered tissues, which span from traditional methods to medical imaging concepts in magnetic resonance elastography, ultrasound elastography, and optical coherence elastography. We focused on the applicability of these methods to the manufacturing of tissue-engineered products online, e.g., if such approach provides a sterile monitoring capacity and is capable of defining mechanical heterogeneity in engineered tissues throughout their growth in vitro in real-time. The review delves into various imaging modalities that employ distinct methods for inducing displacement within the sample, utilizing either strain-based or shear wave-based approaches. This displacement can be achieved through external stimulation or by harnessing ambient vibrations. Subsequently, the imaging process captures and visualizes the resultant displacement. We specifically highlight the advantages of novel non-invasive imaging methods such as ultrasound elastography and optical coherence elastography to assess the mechanical properties of engineered tissues in vitro, as well as their potential applications in cancer study, drug screening and the in vivo evaluation of the engineered tissues.

Exercise MR of Skeletal Muscles, the Heart, and the Brain.

Magnetic resonance (MR) imaging (MRI) is routinely used to evaluate organ morphology and pathology in the human body at rest or in combination with pharmacological stress as an exercise surrogate. With MR during actual physical exercise, we can assess functional characteristics of tissues and organs under real-life stress conditions. This is particularly relevant in patients with limited exercise capacity or exercise intolerance, and where complaints typically present only during physical activity, such as in neuromuscular disorders, inherited metabolic diseases, and heart failure. This review describes practical and physiological aspects of exercise MR of skeletal muscles, the heart, and the brain. The acute effects of physical exercise on these organs are addressed in the light of various dynamic quantitative MR readouts, including phosphorus-31 MR spectroscopy (31P-MRS) of tissue energy metabolism, phase-contrast MRI of blood flow and muscle contraction, real-time cine MRI of cardiac performance, and arterial spin labeling MRI of muscle and brain perfusion. Exercise MR will help advancing our understanding of underlying mechanisms that contribute to exercise intolerance, which often proceed structural and anatomical changes in disease. Its potential to detect disease-driven alterations in organ function, perfusion, and metabolism under physiological stress renders exercise MR stress testing a powerful noninvasive imaging modality to aid in disease diagnosis and risk stratification. Although not yet integrated in most clinical workflows, and while some applications still require thorough validation, exercise MR has established itself as a comprehensive and versatile modality for characterizing physiology in health and disease in a noninvasive and quantitative way. EVIDENCE LEVEL: 5 TECHNICAL EFFICACY: Stage 1.

Imaging CAR-NK cells targeted to HER2 ovarian cancer with human sodium-iodide symporter-based positron emission tomography.

Chimeric antigen receptor (CAR) cell therapies utilize CARs to redirect immune cells towards cancer cells expressing specific antigens like human epidermal growth factor receptor 2 (HER2). Despite their potential, CAR T cell therapies exhibit variable response rates and adverse effects in some patients. Non-invasive molecular imaging can aid in predicting patient outcomes by tracking infused cells post-administration. CAR-T cells are typically autologous, increasing manufacturing complexity and costs. An alternative approach involves developing CAR natural killer (CAR-NK) cells as an off-the-shelf allogeneic product. In this study, we engineered HER2-targeted CAR-NK cells co-expressing the positron emission tomography (PET) reporter gene human sodium-iodide symporter (NIS) and assessed their therapeutic efficacy and PET imaging capability in a HER2 ovarian cancer mouse model.NK-92 cells were genetically modified to express a HER2-targeted CAR, the bioluminescence imaging reporter Antares, and NIS. HER2-expressing ovarian cancer cells were engineered to express the bioluminescence reporter Firefly luciferase (Fluc). Co-culture experiments demonstrated significantly enhanced cytotoxicity of CAR-NK cells compared to naive NK cells. In vivo studies involving mice with Fluc-expressing tumors revealed that those treated with CAR-NK cells exhibited reduced tumor burden and prolonged survival compared to controls. Longitudinal bioluminescence imaging demonstrated stable signals from CAR-NK cells over time. PET imaging using the NIS-targeted tracer 18F-tetrafluoroborate ([18F]TFB) showed significantly higher PET signals in mice treated with NIS-expressing CAR-NK cells.Overall, our study showcases the therapeutic potential of HER2-targeted CAR-NK cells in an aggressive ovarian cancer model and underscores the feasibility of using human-derived PET reporter gene imaging to monitor these cells non-invasively in patients.