Advances In Computed Tomography Research Articles

Liver Fibrosis Conventional and Molecular Imaging Diagnosis Update

Liver fibrosis is a serious, life-threatening disease with high morbidity and mortality that result from diverse causes. Liver biopsy, considered the "gold standard" to diagnose, grade, and stage liver fibrosis, has limitations in terms of invasiveness, cost, sampling variability, inter-observer variability, and the dynamic process of fibrosis. Compelling evidence has demonstrated that all stages of fibrosis are reversible if the injury is removed. There is a clear need for safe, effective, and reliable non-invasive assessment modalities to determine liver fibrosis in order to manage it precisely in personalized medicine. However, conventional imaging methods used to assess morphological and structural changes related to liver fibrosis, including ultrasound, computed tomography (CT), and magnetic resonance imaging (MRI), are only useful in assessing advanced liver disease, including cirrhosis. Functional imaging techniques, including MR elastography (MRE), US elastography, and CT perfusion are useful for assessing moderate to advanced liver fibrosis. MRE is considered the most accurate noninvasive imaging technique, and US elastography is currently the most widely used noninvasive means. However, these modalities are less accurate in early-stage liver fibrosis and some factors affect the accuracy of these techniques. Molecular imaging is a target-specific imaging mechanism that has the potential to accurately diagnose early-stage liver fibrosis. We provide an overview of recent advances in molecular imaging for the diagnosis and staging of liver fibrosis which will enable clinicians to monitor the progression of disease and potentially reverse liver fibrosis. We compare the promising technologies with conventional and functional imaging and assess the utility of molecular imaging in precision and personalized clinical medicine in the early stages of liver fibrosis.

Adverse Effect of the Neuronal Cells and the Coronary Artery Endothelium in Extreme Environments- Roles of Advanced Molecular Imaging Bio-Imaging Markers

Adverse Effect of the Neuronal Cells and the Coronary Artery Endothelium in Extreme Environments- Roles of Advanced Molecular Imaging Bio-Imaging Markers

Cardiovascular calcification: artificial intelligence and big data accelerate mechanistic discovery.

Cardiovascular calcification is a health disorder with increasing prevalence and high morbidity and mortality. The only available therapeutic options for calcific vascular and valvular heart disease are invasive transcatheter procedures or surgeries that do not fully address the wide spectrum of these conditions; therefore, an urgent need exists for medical options. Cardiovascular calcification is an active process, which provides a potential opportunity for effective therapeutic targeting. Numerous biological processes are involved in calcific disease, including matrix remodelling, transcriptional regulation, mitochondrial dysfunction, oxidative stress, calcium and phosphate signalling, endoplasmic reticulum stress, lipid and mineral metabolism, autophagy, inflammation, apoptosis, loss of mineralization inhibition, impaired mineral resorption, cellular senescence and extracellular vesicles that act as precursors of microcalcification. Advances in molecular imaging and big data technology, including in multiomics and network medicine, and the integration of these approaches are helping to provide a more comprehensive map of human disease. In this Review, we discuss ectopic calcification processes in the cardiovascular system, with an emphasis on emerging mechanistic knowledge obtained through patient data and advances in imaging methods, experimental models and multiomics-generated big data. We also highlight the potential and challenges of artificial intelligence, machine learning and deep learning to integrate imaging and mechanistic data for drug discovery.

Dose Reduction Methods in Chest Computed Tomography

Introduction: Computed tomography is one of the most powerful tools for investigating thorax disease, because it shows progression of lung disease much clearer than chest radiography. Technical advances in CT scanners have led to some abilities for CT scanners such as coverage of larger volume, lower noise and ability for acquiring image in one respiratory phase. However, this will be accompanied by more radiation exposure to patient and research shows that CT gives higher exposure dose to patient in comparison with conventional radiography.1 Materials and Methods: In each computed tomography (CT), patient dose is dependent on the scan parameters. Scan parameters are included kV, mA, scan field of view (SFOV), rotation time, focal spot size, slice width and pitch. Also, shielding of sensitive organs such as breast which is not interest organ during chest CT scanning is one of the dose reduction methods. Furthermore, Type of scanner, methods and protocols of scanning, for example in multi-slice scanners there is some more cases like collimation, which effect on patient dose, and therefore all of these options should be adjusted, accurately. It is considerable that scan parameters such as reconstructed matrix and reconstruction algorithms have considered in this paper; however, these parameters do not impact directly on patient dose but they have some affects through changing the characteristics of the image indirectly. In this study twenty methods for radiation dose reduction in thorax CT were explained. Conclusion: According to the principle of ALARA, the aim of applying optimization techniques is to reduce the amount of receiving dose while maintaining image quality.

Evaluation of a novel photon-counting CT system using a 16-channel MPPC array for multicolor 3-D imaging

Abstract X-ray computed tomography (CT) has been widely used in the diagnostic imaging of the interior of the human body. However, the radiation dose of conventional CT typically amounts to 10 mSv. Under such environments, X-ray photons are severely piled-up; therefore, conventional CT acquires energy integrated images, and artifacts are formed by beam hardening. In contrast, a photon counting CT (PC-CT) system is anticipated to construct a low-dose and multi-color CT system. Recently, we proposed a novel PC-CT system using a multipixel photon counter (MPPC) coupled with a high-speed scintillator , which is cost effective and easy to assemble compared to other methods using CdZnTe device. In this paper, we report the results using an advanced CT system consisting of a 16-channel MPPC and scintillator array coupled with a newly developed large-scale integrated circuit (LSI) having an ultrafast signal processing capability. We present the performance of the photon-counting CT capability, such as the contrast of the obtained CT images compared with that of the current-mode CT, and we found that substantial reduction in radiation dose by an order of magnitude. In addition, we report the results of three-dimensional multicolor imaging to identify phantom materials.

Prostate-specific membrane antigen for prostate cancer theranostics: from imaging to targeted therapy.

In recent years, major advances in molecular imaging of prostate cancers (PCa) were made with the development and clinical validation of highly accurate PET tracers to stage and restage the disease. Prostate-specific membrane antigen (PSMA) is a transmembrane protein highly expressed in PCa, and its expression has led to the development of PSMA-binding radiopharmaceuticals for molecular imaging or radioligand therapy (RLT). We herein review the recent literature published on diagnostic and therapeutic (i.e. theranostic) PSMA tracers. Development in small PSMA-targeted molecules labeled with gallium-68 and fluorine-18 show promising results for primary staging and detection of disease at biochemical recurrence using PET/computed tomography (PET/CT). Studies show a higher sensitivity and specificity, along with an improved detection rate over conventional imaging (CT scan and bone scan) or choline PET tracers, especially for restaging after prostate-specific antigen failure following loco-regional therapy. In addition, some PSMA tracers can be labeled with beta-minus and alpha particle emitters, yielding encouraging response rates and low toxicity, and potentially offering a new line of targeted therapy for metastatic castration-resistant PCa. PSMA-targeted tracers have shown unprecedented accuracy to stage and restage PCa using PET/CT. Given their specific biodistribution toward PCa tissue, PSMA RLT now offers new therapeutic possibilities to target metastatic PCa. Prospective multicenter randomized studies investigating the clinical impact of PSMA-targeted molecules are urgently needed.

Harness the Power of Upconversion Nanoparticles for Spectral Computed Tomography Diagnosis of Osteosarcoma

AbstractOsteosarcoma, as the most common primary bone cancer, is difficult to make a differentiation between tumor with contrast agents (CAs) accumulation and healthy bones using X‐ray computed tomography (CT) since they both display high attenuation of X‐ray. Recently, an advanced CT form, gemstone spectral CT (GSCT), has received extensive attention due to its significant ability of material decomposition and monochromatic images, which can overcome the above disadvantages of conventional CT. Herein, the lutecium (Lu)‐based upconversion nanoparticles (UCNPs, polyethylene glycol (PEG)–NaLuF4:Yb/Er), which possess great spectral CT performance over clinical used iohexol, is investigated as a novel kind of spectral CT CAs in the diagnosis of osteosarcoma. Both in vitro and in vivo experiments show that Lu‐based UCNPs provided much more diagnostic interpretation, and can successfully distinguish the osteosarcoma from the surround bones with GSCT while the iohexol fails due to the different X‐ray attenuation characteristics of UCNPs (i.e., lutecium) and iohexol (e.g., iodine) under different energy. As a proof of concept, the Lu‐based UCNPs with excellent biocompatibility hold great potential for further clinical diagnosis of skeletal system diseases.

Synthesis of PEGylated Semiconducting Polymer Amphiphiles for Molecular Photoacoustic Imaging and Guided Therapy.

Semiconducting polymer nanoparticles (SPNs) have been used as a new class of photonic materials with great potential in biomedical applications, but their synthetic method is limited to nanoprecipitation. Semiconducting polymer amphiphiles (SPAs) that can spontaneously self-assemble into nanoparticles are ideal alternatives for SPNs. Depending on their backbone structures, SPAs with different optical properties can be developed into nanoprobes for molecular imaging applications such as photoacoustic (PA) and fluorescence imaging as well as photothermal therapy. In this Concept, recent studies on the synthesis of SPAs for PA imaging and guided cancer therapy are summarized. The effect of grafting density on the optical properties of SPAs is discussed, and the nanoparticle sizes of SPAs can be reduced by utilization of a short semiconducting oligomer. Moreover, SPAs can be developed into PA theranostic platform and activatable PA nanoprobes. These studies demonstrate that SPAs are promising for advanced molecular imaging and therapy applications.

Animal models for the study of inflammatory bowel diseases: a meta-analysis on modalities for imaging inflammatory lesions.

Inflammatory bowel diseases are lifelong disorders affecting the gastrointestinal tract characterized by intermittent disease flares and periods of remission with a progressive and destructive nature. Unfortunately, the exact etiology is still not completely known, therefore a causal therapy to cure the disease is not yet available. Current treatment options mainly encompass the use of non-specific anti-inflammatory agents and immunosuppressive drugs that cause significant side effects that often have a negative impact on patients' quality of life. As the majority of patients need a long-term follow-up it would be ideal to rely on a non-invasive technique with good compliance. Currently, the gold standard diagnostic tools for managing IBD are represented by invasive procedures such as colonoscopy and histopathology. Nevertheless, recent advances in imaging technology continue to improve the ability of imaging techniques to non-invasively monitor disease activity and treatment response in preclinical models of IBD. Novel and emerging imaging techniques not only allow direct visualization of intestinal inflammation, but also enable molecular imaging and targeting of specific alterations of the inflamed murine mucosa. Furthermore, molecular imaging advances allow us to increase our knowledge on the critical biological pathways involved in disease progression by characterizing in vivo processes at a cellular and molecular level and enabling significant improvements in the understanding of the etiology of IBD. This review presents a critical and updated overview on the imaging advances in animal models of IBD. Our aim is to highlight the potential beneficial impact and the range of applications that imaging techniques could offer for the improvement of the clinical monitoring and management of IBD patients: diagnosis, staging, determination of therapeutic targets, monitoring therapy and evaluation of the prognosis, personalized therapeutic approaches.

DNA Aptamer-Based Activatable Probes for Photoacoustic Imaging in Living Mice.

DNA aptamers are a powerful class of molecules for sensing targets, but have been limited when applied to imaging in living animals because most aptamer probes are fluorescence-based, which limits imaging penetration depth. Photoacoustic (PA) imaging emerged as an alternative to MRI and X-ray tomography in biomedical imaging, due to its ability to afford high-resolution images at depths in the cm range. Despite its promise, PA imaging is limited by a lack of strategies to design selective and activatable probes for targets. To overcome this limitation, we report design and demonstration of PA probes based on DNA aptamers that can hybridize to DNA strands conjugated to a near-infrared fluorophore/quencher pair (IRDye 800CW/IRDye QC-1) with efficient contact quenching. Binding of the target triggered a release of the DNA strand with the quencher and thus relief of the contact quenching, resulting in a change of the PA signal ratio at 780/725 nm. Using thrombin as a model, a relationship was established between the thrombin concentrations and the PA ratio, with a dynamic range of 0–1000 nM and a limit of detection of 112 nM. Finally, in vivo PA imaging studies showed that the PA ratio increased significantly 45 min after injection of thrombin but not with injection of PBS as a vehicle control, demonstrating the first aptamer-based activatable PA probe for advanced molecular imaging in living mice. Since in vitro selection can obtain aptamers selective for many targets, the design demonstrated can be applied for PA imaging of a number of targets.

Photoacoustic Imaging of Embryonic Stem Cell-Derived Cardiomyocytes in Living Hearts with Ultrasensitive Semiconducting Polymer Nanoparticles.

The last decade has seen impressive progress in human embryonic stem cell-derived cardiomyocytes (hESC-CMs) that makes them ideal tools to repair injured hearts. To achieve an optimal outcome, advanced molecular imaging methods are essential to accurately track these transplanted cells in the heart. Herein, we demonstrate for the first time that a class of photoacoustic nanoparticles (PANPs) incorporating semiconducting polymers (SPs) as contrast agents can be used in the photoacoustic imaging (PAI) of transplanted hESC-CMs in living mouse hearts. This is achieved by virtue of two benefits of PANPs. First, strong PA signals and specific spectral features of SPs allow PAI to sensitively detect and distinguish a small number of PANP-labeled cells (2,000) from background tissues in vivo. Second, the PANPs show a high efficiency for hESC-CM labeling without adverse effects on cell structure, function, and gene expression. Assisted by ultrasound imaging, the delivery and engraftment of hESC-CMs in living mouse hearts can be assessed by PANP-based PAI with high spatial resolution (~100 μm). In summary, this study explores and validates a novel application of SPs as a PA contrast agent to track labeled cells with high sensitivity and accuracy in vivo, highlighting the advantages of integrating PAI and PANPs to advance cardiac regenerative therapies.

Molecular imaging of advanced thyroid cancer: iodinated radiotracers and beyond.

An important aspect of differentiated thyroid cancer (DTC) management is disease localization by imaging. Functional imaging of thyroid cancer with iodinated radiotracers has been employed for metastatic disease detection for long. More recently, 2-deoxy-2-[18F] fluoro-D-glucose (18F-FDG) positron emission tomography/computed tomography (PET/CT), a non-iodinated ubiquitous PET tracer, has been used to detect non-radioiodine (RAI) avid disease. Advances in molecular imaging have led to the development of newer tracers like 18F-TFB (18F-tetrafluoroborate) that are transported through the sodium-iodide symporter (NIS) as well as 68Ga-DOTATATE that image the somatostatin receptors sub-type 2 expressed in medullary thyroid cancer and some DTC. In coming years, there will be focus on newer receptor targets like prostate-specific membrane antigen expression and endoradiotherapies and theranostics.

Nuclear and Fluorescent Labeled PD-1-Liposome-DOX-64Cu/IRDye800CW Allows Improved Breast Tumor Targeted Imaging and Therapy.

The overexpression of programmed cell death-1 (PD-1) in tumors as breast cancer makes it a possible target for cancer imaging and therapy. Advances in molecular imaging, including radionuclide imaging and near-infrared fluorescence (NIRF) imaging, enable the detection of tumors with high sensitivity. In this study, we aim to develop a novel PD-1 antibody targeted positron emission tomography (PET) and NIRF labeled liposome loaded with doxorubicin (DOX) and evaluate its application for in vivo cancer imaging and therapy. IRDye800CW and 64Cu were conjugated to liposomes with PD-1 antibody labeling, and DOX was inside the liposomes to form theranostic nanoparticles. The 4T1 tumors were successfully visualized with PD-1-Liposome-DOX-64Cu/IRDye800CW using NIRF/PET imaging. The bioluminescent imaging (BLI) results showed that tumor growth was significantly inhibited in the PD-1-Liposome-DOX-treated group than the IgG control. Our results highlight the potential of using dual-labeled theranostic PD-1 mAb-targeted Liposome-DOX-64Cu/IRDye800CW for the management of breast tumor.

Beyond the androgen receptor II: New approaches to understanding and treating metastatic prostate cancer; Report from the 2017 Coffey-Holden Prostate Cancer Academy Meeting.

The 2017 Coffey-Holden Prostate Cancer Academy (CHPCA) Meeting, "Beyond the Androgen Receptor II: New Approaches to Understanding and Treating Metastatic Prostate Cancer," was held in Carlsbad, California from June 14-17, 2017. The CHPCA is an annual scientific conference hosted by the Prostate Cancer Foundation (PCF) that is uniquely designed to produce extensive and constructive discussions on the most urgent and impactful topics concerning research into the biology and treatment of metastatic prostate cancer. The 2017 CHPCA Meeting was the 5th meeting in this annual series and was attended by 71 investigators focused on prostate cancer and a variety of other fields including breast and ovarian cancer. The discussions at the meeting were concentrated on topics areas including: mechanisms and therapeutic approaches for molecular subclasses of castrate resistant prostate cancer (CRPC), the epigenetic landscape of prostate cancer, the role of DNA repair gene mutations, advancing the use of germline genetics in clinical practice, radionuclides for imaging and therapy, advances in molecular imaging, and therapeutic strategies for successful use of immunotherapy in advanced prostate cancer. This article reviews the presentations and discussions from the 2017 CHPCA Meeting in order to disseminate this knowledge and accelerate new biological understandings and advances in the treatment of patients with metastatic prostate cancer.

CT coronary imaging-a fast evolving world.

Computed tomography (CT) has become an important modality in the evaluation of coronary artery disease (CAD). The tremendous technological advances in CT in the last two decades has made it possible to obtain high quality images of coronary arteries with high spatial and temporal resolutions. Multiple trials have confirmed the accuracy of CT compared to invasive catheter angiography. CT is also able to evaluate beyond the lumen in characterizing and quantifying atherosclerotic plaques, including evaluation of high risk features. Although CTA has low specificity in identification of lesion-specific ischemia, functional techniques are now possible such as CT myocardial perfusion and CT-fractional flow reserve (FFR) which evaluate the hemodynamic significance of stenosis and help with revascularization strategies. Multi-energy CT provides additional information beyond what is possible with a conventional CT and is useful in variety of clinical applications, including myocardial perfusion imaging, lesion characterization and low contrast studies. Large trials have confirmed the ability of CT to predict major adverse cardiovascular events and recent trials have even demonstrated improved clinical outcomes by using CT for the evaluation of CAD. CT is also useful in structural heart disease and 3 D printing is now increasingly used for surgical/interventional planning. Machine learning is evolving rapidly and is likely to impact diagnosis and management.

Molecular Imaging and Updated Diagnostic Criteria in Lewy Body Dementias.

The aims of the study were to review recent advances in molecular imaging in the Lewy body dementias (LBD) and determine if these may support the clinical but contested temporal profile distinction between Parkinson disease (PD) with dementia (PDD) versus dementia with Lewy bodies (DLB). There do not appear to be major regional cerebral metabolic or neurotransmitter distinctions between PDD and DLB. However, recent studies highlight the relative discriminating roles of Alzheimer proteinopathies. PDD patients have lower cortical β-amyloid deposition than DLB. Preliminary tau PET studies suggest a gradient of increasing tau binding from cognitively normal PD (absent to lowest) to cognitively impaired PD (low) to DLB (intermediate) to Alzheimer disease (AD; highest). However, tau binding in DLB, including the medial temporal lobe, is substantially lower than in AD. Alzheimer-type proteinopathies appear to be more common in DLB compared to PDD with relative but no absolute differences. Given the spectrum of overlapping pathologies, future α-synuclein ligands are expected to have the best potential to distinguish the LBD from pure AD.

Management of incidental pulmonary embolism

Incidental pulmonary embolism (PE) is a frequent finding on routine computed tomography (CT) scans of the chest, occurring in 1.1% of coronary CT scans and 3.6% of oncological CT scans. Despite this high frequency, optimal management of incidental PE has not been addressed in clinical trials and remains the subject of debate. Although these CT scans have not been performed with a dedicated PE protocol and have suboptimal contrast enhancement, diagnosis of incidental PE has been shown to be accurate up to the segmental and subsegmental arteries. The embolic load in incidental PE is lower than that in symptomatic PE. Even so, observational studies suggest that the natural course of incidental PE is similar to that of symptomatic PE with regard to the risk of recurrent venous thrombotic disease and mortality. Interestingly, the increased use of more advanced CT technology has coincided with an increase in the rate of incidental subsegmental PE, as is the case for symptomatic subsegmental PE. Although clinical trials are lacking, and observational data are limited to cancer-associated incidental PE, the consensus is that the management of incidental PE is identical to that of symptomatic PE, including the choice of optimal drug class, outpatient treatment and total duration of treatment.

Ultrasound molecular imaging

Non-invasive in vivo molecular imaging technologies are uniquely poised to be able to temporally evaluate vascular adaptations to disease and the impact of new therapies. These technologies have been used to study vascular changes in various forms of cardiovascular and inflammatory disease and cancer. The approaches for studying the macro- or microvasculature with non-invasive imaging go beyond anatomic or perfusion characterization and instead yield information on vascular phenotype by either analyzing novel signal features or using targeted contrast agents that reveal the molecular underpinnings for disease. This talk will review new developments in ultrasound molecular imaging techniques that are likely to have a substantial impact on the understanding of pathophysiology, the development of new therapies, or diagnosis of disease in patients. Topics of focus will include recent advances in molecular imaging for the evaluation of: (1) atherosclerotic disease, (2) tissue inflammation or ischemic injury; and (3) thrombus or prothrombotic environment, (4) angiogenesis and stem cells. The discussion will also include a discussion of how these different approaches may play a role to solve current clinical deficiencies.

Development of Semiconducting Polymer Nanoparticles for Photoacoustic Imaging

Semiconducting polymer nanoparticles (SPNs) have evolved into a new class of photonic materials with great potential for biomedical applications. Depending on the polymer structures, SPNs can be developed into optical agents for fluorescence and chemiluminescence imaging, photosensitizers for photodynamic therapy, and heat converters for photothermal therapy. In this feature article, recent work is summarized on the development of SPNs for in vivo photoacoustic (PA) imaging, a state-of-the-art imaging modality that converts light energy into mechanical acoustic waves to provide deep tissue penetration. The structure-property relationship and doping approaches are discussed to reveal the importance of promoting nonradiative decay in amplifying the PA brightness of SPNs. Moreover, their imaging applications, including lymph node mapping, tumor imaging, and monitoring of pathological indexes, are highlighted. These studies demonstrate that SPNs can serve as versatile PA agents for advanced molecular imaging applications.

Defining Clinical Response Criteria and Early Response Criteria for Precision Oncology: Current State-of-the-Art and Future Perspectives.

In this era of precision oncology, there has been an exponential growth in the armamentarium of genomically targeted therapies and immunotherapies. Evaluating early responses to precision therapy is essential for “go” versus “no go” decisions for these molecularly targeted drugs and agents that arm the immune system. Many different response assessment criteria exist for use in solid tumors and lymphomas. We reviewed the literature using the Medline/PubMed database for keywords “response assessment” and various known response assessment criteria published up to 2016. In this article we review the commonly used response assessment criteria. We present a decision tree to facilitate selection of appropriate criteria. We also suggest methods for standardization of various response assessment criteria. The relevant response assessment criteria were further studied for rational of development, key features, proposed use and acceptance by various entities. We also discuss early response evaluation and provide specific case studies of early response to targeted therapy. With high-throughput, advanced computing programs and digital data-mining it is now possible to acquire vast amount of high quality imaging data opening up a new field of “omics in radiology”—radiomics that complements genomics for personalized medicine. Radiomics is rapidly evolving and is still in the research arena. This cutting-edge technology is poised to move soon to the mainstream clinical arena. Novel agents with new mechanisms of action require advanced molecular imaging as imaging biomarkers. There is an urgent need for development of standardized early response assessment criteria for evaluation of response to precision therapy.