Open AccessReview
First- and Second-Line Targeted Systemic Therapy in Hepatocellular Carcinoma—An Update on Patient Selection and Response Evaluation
Diagnostics 2016, 6(4), 44; doi:10.3390/diagnostics6040044 -
Abstract
Advanced hepatocellular carcinoma (HCC) with vascular invasion and/or extrahepatic spread and preserved liver function, according to stage C of the Barcelona Clinic Liver Cancer (BCLC) classification, has a dismal prognosis. The multi-targeted tyrosine-kinase receptor inhibitor (TKI) sorafenib is the only proven active substance
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Advanced hepatocellular carcinoma (HCC) with vascular invasion and/or extrahepatic spread and preserved liver function, according to stage C of the Barcelona Clinic Liver Cancer (BCLC) classification, has a dismal prognosis. The multi-targeted tyrosine-kinase receptor inhibitor (TKI) sorafenib is the only proven active substance in systemic HCC therapy for first-line treatment. In this review, we summarize current aspects in patient selection and management of side effects, and provide an update on response evaluation during first-line sorafenib therapy. Since second-line treatment options have been improved with the successful completion of the RESORCE trial, demonstrating a survival benefit for second-line treatment with the TKI regorafenib, response monitoring during first-line therapy will be critical to deliver optimal systemic therapy in HCC. To this regard, specific side effects, in particular worsening of arterial hypertension and diarrhea, might suggest treatment response during first-line sorafenib therapy; however, clear predictive clinical markers, as well as laboratory test or serum markers, are not established. Assessment of radiologic response according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST) is helpful to identify patients who do not benefit from sorafenib treatment. Full article
Open AccessReview
Gold Nanoparticles for Diagnostics: Advances towards Points of Care
Diagnostics 2016, 6(4), 43; doi:10.3390/diagnostics6040043 -
Abstract
The remarkable physicochemical properties of gold nanoparticles (AuNPs) have prompted developments in the exploration of biomolecular interactions with AuNP-containing systems, in particular for biomedical applications in diagnostics. These systems show great promise in improving sensitivity, ease of operation and portability. Despite this endeavor,
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The remarkable physicochemical properties of gold nanoparticles (AuNPs) have prompted developments in the exploration of biomolecular interactions with AuNP-containing systems, in particular for biomedical applications in diagnostics. These systems show great promise in improving sensitivity, ease of operation and portability. Despite this endeavor, most platforms have yet to reach maturity and make their way into clinics or points of care (POC). Here, we present an overview of emerging and available molecular diagnostics using AuNPs for biomedical sensing that are currently being translated to the clinical setting. Full article
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Open AccessReview
Targeted Molecular Imaging in Adrenal Disease—An Emerging Role for Metomidate PET-CT
Diagnostics 2016, 6(4), 42; doi:10.3390/diagnostics6040042 -
Abstract
Adrenal lesions present a significant diagnostic burden for both radiologists and endocrinologists, especially with the increasing number of adrenal ‘incidentalomas’ detected on modern computed tomography (CT) or magnetic resonance imaging (MRI). A key objective is the reliable distinction of benign disease from either
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Adrenal lesions present a significant diagnostic burden for both radiologists and endocrinologists, especially with the increasing number of adrenal ‘incidentalomas’ detected on modern computed tomography (CT) or magnetic resonance imaging (MRI). A key objective is the reliable distinction of benign disease from either primary adrenal malignancy (e.g., adrenocortical carcinoma or malignant forms of pheochromocytoma/paraganglioma (PPGL)) or metastases (e.g., bronchial, renal). Benign lesions may still be associated with adverse sequelae through autonomous hormone hypersecretion (e.g., primary aldosteronism, Cushing’s syndrome, phaeochromocytoma). Here, identifying a causative lesion, or lateralising the disease to a single adrenal gland, is key to effective management, as unilateral adrenalectomy may offer the potential for curing conditions that are typically associated with significant excess morbidity and mortality. This review considers the evolving role of positron emission tomography (PET) imaging in addressing the limitations of traditional cross-sectional imaging and adjunctive techniques, such as venous sampling, in the management of adrenal disorders. We review the development of targeted molecular imaging to the adrenocortical enzymes CYP11B1 and CYP11B2 with different radiolabeled metomidate compounds. Particular consideration is given to iodo-metomidate PET tracers for the diagnosis and management of adrenocortical carcinoma, and the increasingly recognized utility of 11C-metomidate PET-CT in primary aldosteronism. Full article
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Open AccessArticle
Gingival Crevicular Fluid as a Novel Potential Source of Biomarkers Distinguishes Pubertal from Post-Pubertal Subjects
Diagnostics 2016, 6(4), 41; doi:10.3390/diagnostics6040041 -
Abstract
Detection of pubertal growth peak is vital in orthodontic treatment timing and planning. Gingival crevicular fluid (GCF) contains abundant proteins from different sources and has been proven to be an ideal source of biomarkers. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF/MS) is an
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Detection of pubertal growth peak is vital in orthodontic treatment timing and planning. Gingival crevicular fluid (GCF) contains abundant proteins from different sources and has been proven to be an ideal source of biomarkers. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF/MS) is an advanced technique that can detect low-molecular-weight peptides with high sensitivity and resolution. The aim of this research was to identify novel candidate biomarkers in GCF to help the diagnosis of pubertal growth peak by MALDI-TOF/MS. Results showed that the peak intensities of six peptides were significantly different between two groups: 1660.2 Da, 1783.0 Da, 2912.5 Da, 4178.6 Da, 5064.9 Da, and 6108.9 Da and are considered to be potential candidate biomarkers to identify pubertal growth peak. Further studies are needed to identify sequence information of these candidate biomarkers. Full article
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Open AccessArticle
Endogenous Intoxication and Saliva Lipid Peroxidation in Patients with Lung Cancer
Diagnostics 2016, 6(4), 39; doi:10.3390/diagnostics6040039 -
Abstract
This research was aimed at a search for regularities in changes to parameters of endogenous intoxication and saliva lipid peroxidation in patients with lung cancer, non-malignant lung diseases, and apparently healthy people. All patients went through saliva sampling at an amount of 1
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This research was aimed at a search for regularities in changes to parameters of endogenous intoxication and saliva lipid peroxidation in patients with lung cancer, non-malignant lung diseases, and apparently healthy people. All patients went through saliva sampling at an amount of 1 mL. A concentration of malondialdehyde (MDA) was measured according to a reaction with thiobarbituric acid, and a level of middle molecules (MM) was measured with UV spectroscopy at 254 and 280 nm, while the content of lipid peroxidation products was measured according to a degree of heptane extract light absorption at wavelengths of 220, 232, 278, and 400 nm. It has been revealed that in the context of lung cancer, the level of diene conjugates decreases, increasing the level of triene conjugates, Schiff’s bases, and MM. As a tumor grows, there is a decrease in the level of lipid peroxidation primary products and an increase in endotoxemia phenomena. The process is more apparent when going from local to locally advanced disease states. The nature of the MDA change is nonlinearly associated with tumor progression. The findings might be used to optimize traditional aids of diagnostics, in disease state forecasting, in treatment monitoring, etc. Full article
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Open AccessArticle
The Effect of Exercise on Salivary Viscosity
Diagnostics 2016, 6(4), 40; doi:10.3390/diagnostics6040040 -
Abstract
A common experience after exercise is the presence of a thick and sticky saliva layer on the oral surfaces, which causes a feeling of a dry mouth. Since the salivary mucin MUC5B is responsible for the visco-elastic behavior of saliva, in the present
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A common experience after exercise is the presence of a thick and sticky saliva layer on the oral surfaces, which causes a feeling of a dry mouth. Since the salivary mucin MUC5B is responsible for the visco-elastic behavior of saliva, in the present study we explored the effect of exercise on both the salivary viscosity and the secretion of MUC5B in saliva. Twenty healthy dental students performed an aerobic exercise by cycling for 15 min on cycle-ergometers at a heart rate of 130–140 beats per minute. Saliva was collected at three time points: before exercise, immediately after exercise and after 30 min recovery. Salivary flow rate, viscosity, amylase activity, total protein, carbohydrate and MUC5B concentration were determined. Salivary flow rate, protein and amylase did not change significantly. Immediately after exercise, the salivary viscosity and carbohydrate concentration were significantly higher than at baseline and after 30 min recovery. Immediately after exercise, the MUC5B concentration was significantly higher than after 30 min recovery. It is concluded that the presence of thick saliva after exercise is at least partially due to an increased secretion of MUC5B. Full article
Open AccessArticle
Exploring the Limits of Cell Adhesion under Shear Stress within Physiological Conditions and beyond on a Chip
Diagnostics 2016, 6(4), 38; doi:10.3390/diagnostics6040038 -
Abstract
Cell adhesion processes are of ubiquitous importance for biomedical applications such as optimization of implant materials. Here, not only physiological conditions such as temperature or pH, but also topographical structures play crucial roles, as inflammatory reactions after surgery can diminish osseointegration. In this
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Cell adhesion processes are of ubiquitous importance for biomedical applications such as optimization of implant materials. Here, not only physiological conditions such as temperature or pH, but also topographical structures play crucial roles, as inflammatory reactions after surgery can diminish osseointegration. In this study, we systematically investigate cell adhesion under static, dynamic and physiologically relevant conditions employing a lab-on-a-chip system. We screen adhesion of the bone osteosarcoma cell line SaOs-2 on a titanium implant material for pH and temperature values in the physiological range and beyond, to explore the limits of cell adhesion, e.g., for feverish and acidic conditions. A detailed study of different surface roughness Rq gives insight into the correlation between the cells’ abilities to adhere and withstand shear flow and the topography of the substrates, finding a local optimum at Rq = 22 nm. We use shear stress induced by acoustic streaming to determine a measure for the ability of cell adhesion under an external force for various conditions. We find an optimum of cell adhesion for T = 37 °C and pH = 7.4 with decreasing cell adhesion outside the physiological range, especially for high T and low pH. We find constant detachment rates in the physiological regime, but this behavior tends to collapse at the limits of 41 °C and pH 4. Full article
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Open AccessReview
Fluid Biomarkers of Traumatic Brain Injury and Intended Context of Use
Diagnostics 2016, 6(4), 37; doi:10.3390/diagnostics6040037 -
Abstract
Traumatic brain injury (TBI) is one of the leading causes of death and disability around the world. The lack of validated biomarkers for TBI is a major impediment to developing effective therapies and improving clinical practice, as well as stimulating much work in
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Traumatic brain injury (TBI) is one of the leading causes of death and disability around the world. The lack of validated biomarkers for TBI is a major impediment to developing effective therapies and improving clinical practice, as well as stimulating much work in this area. In this review, we focus on different settings of TBI management where blood or cerebrospinal fluid (CSF) biomarkers could be utilized for predicting clinically-relevant consequences and guiding management decisions. Requirements that the biomarker must fulfill differ based on the intended context of use (CoU). Specifically, we focus on fluid biomarkers in order to: (1) identify patients who may require acute neuroimaging (cranial computerized tomography (CT) or magnetic resonance imaging (MRI); (2) select patients at risk for secondary brain injury processes; (3) aid in counseling patients about their symptoms at discharge; (4) identify patients at risk for developing postconcussive syndrome (PCS), posttraumatic epilepsy (PTE) or chronic traumatic encephalopathy (CTE); (5) predict outcomes with respect to poor or good recovery; (6) inform counseling as to return to work (RTW) or to play. Despite significant advances already made from biomarker-based studies of TBI, there is an immediate need for further large-scale studies focused on identifying and innovating sensitive and reliable TBI biomarkers. These studies should be designed with the intended CoU in mind. Full article
Open AccessReview
The Role of PET/CT Molecular Imaging in the Diagnosis of Recurrence and Surveillance of Patients Treated for Non-Small Cell Lung Cancer
Diagnostics 2016, 6(4), 36; doi:10.3390/diagnostics6040036 -
Abstract
Non-small cell lung cancer (NSCLC) is the leading cause of cancer mortality worldwide and its prognosis remains poor. Molecular imaging with 18F-FDG PET/CT can metabolically characterize the nature of lesions as benign or malignant, allowing a better staging at the diagnosis of
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Non-small cell lung cancer (NSCLC) is the leading cause of cancer mortality worldwide and its prognosis remains poor. Molecular imaging with 18F-FDG PET/CT can metabolically characterize the nature of lesions as benign or malignant, allowing a better staging at the diagnosis of this kind of patient. This advantage can also be applied in the re-staging due to the suspicion of recurrent disease. Many patients have a recurrence of the disease, including surgically treated patients. In the current context, with new personalized oncological treatments, the surveillance for recurrence and its accurate diagnosis are crucial to improve their survival. In this paper, we revise the current knowledge about the clinical and molecular factors related to the recurrent disease. In the context of new, promising, available personalized treatments, the role of molecular imaging with PET/CT and 18F-FDG and non-18F-FDG radiotracers in the follow-up of NSCLC-treated patients is especially attractive and interesting. Full article
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Open AccessReview
Clinical Utility of Positron Emission Tomography Magnetic Resonance Imaging (PET-MRI) in Gastrointestinal Cancers
Diagnostics 2016, 6(3), 35; doi:10.3390/diagnostics6030035 -
Abstract
Anatomic imaging utilizing both CT (computed tomography) and MRI (magnetic resonance imaging) limits the assessment of cancer metastases in lymph nodes and distant organs while functional imaging like PET (positron emission tomography) scan has its limitation in spatial resolution capacity. Hybrid imaging utilizing
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Anatomic imaging utilizing both CT (computed tomography) and MRI (magnetic resonance imaging) limits the assessment of cancer metastases in lymph nodes and distant organs while functional imaging like PET (positron emission tomography) scan has its limitation in spatial resolution capacity. Hybrid imaging utilizing PET-CT and PET-MRI are novel imaging modalities that are changing the current landscape in cancer diagnosis, staging, and treatment response. MRI has shown to have higher sensitivity in soft tissue, head and neck pathology, and pelvic disease, as well as, detecting small metastases in the liver and bone compared to CT. Combining MRI with PET allows for detection of metastases that may have been missed with current imaging modalities. In this review, we will examine the clinical utility of FDG PET-MRI in the diagnosis and staging of gastrointestinal cancers with focus on esophageal, stomach, colorectal, and pancreatic cancers. We will also explore its role in treatment response and future directions associated with it. Full article
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Open AccessReview
Dynamic Contrast-Enhanced CT in Patients with Pancreatic Cancer
Diagnostics 2016, 6(3), 34; doi:10.3390/diagnostics6030034 -
Abstract
The aim of this systematic review is to provide an overview of the use of Dynamic Contrast-enhanced Computed Tomography (DCE-CT) in patients with pancreatic cancer. This study was composed according to the PRISMA guidelines 2009. The literature search was conducted in PubMed, Cochrane
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The aim of this systematic review is to provide an overview of the use of Dynamic Contrast-enhanced Computed Tomography (DCE-CT) in patients with pancreatic cancer. This study was composed according to the PRISMA guidelines 2009. The literature search was conducted in PubMed, Cochrane Library, EMBASE, and Web of Science databases to identify all relevant publications. The QUADAS-2 tool was implemented to assess the risk of bias and applicability concerns of each included study. The initial literature search yielded 483 publications. Thirteen articles were included. Articles were categorized into three groups: nine articles concerning primary diagnosis or staging, one article about tumor response to treatment, and three articles regarding scan techniques. In exocrine pancreatic tumors, measurements of blood flow in eight studies and blood volume in seven studies were significantly lower in tumor tissue, compared with measurements in pancreatic tissue outside of tumor, or normal pancreatic tissue in control groups of healthy volunteers. The studies were heterogeneous in the number of patients enrolled and scan protocols. Perfusion parameters measured and analyzed by DCE-CT might be useful in the investigation of characteristic vascular patterns of exocrine pancreatic tumors. Further clinical studies are desired for investigating the potential of DCE-CT in pancreatic tumors. Full article
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Open AccessArticle
Evolvable Smartphone-Based Platforms for Point-of-Care In-Vitro Diagnostics Applications
Diagnostics 2016, 6(3), 33; doi:10.3390/diagnostics6030033 -
Abstract
The association of smart mobile devices and lab-on-chip technologies offers unprecedented opportunities for the emergence of direct-to-consumer in vitro medical diagnostics applications. Despite their clear transformative potential, obstacles remain to the large-scale disruption and long-lasting success of these systems in the consumer market.
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The association of smart mobile devices and lab-on-chip technologies offers unprecedented opportunities for the emergence of direct-to-consumer in vitro medical diagnostics applications. Despite their clear transformative potential, obstacles remain to the large-scale disruption and long-lasting success of these systems in the consumer market. For instance, the increasing level of complexity of instrumented lab-on-chip devices, coupled to the sporadic nature of point-of-care testing, threatens the viability of a business model mainly relying on disposable/consumable lab-on-chips. We argued recently that system evolvability, defined as the design characteristic that facilitates more manageable transitions between system generations via the modification of an inherited design, can help remedy these limitations. In this paper, we discuss how platform-based design can constitute a formal entry point to the design and implementation of evolvable smart device/lab-on-chip systems. We present both a hardware/software design framework and the implementation details of a platform prototype enabling at this stage the interfacing of several lab-on-chip variants relying on current- or impedance-based biosensors. Our findings suggest that several change-enabling mechanisms implemented in the higher abstraction software layers of the system can promote evolvability, together with the design of change-absorbing hardware/software interfaces. Our platform architecture is based on a mobile software application programming interface coupled to a modular hardware accessory. It allows the specification of lab-on-chip operation and post-analytic functions at the mobile software layer. We demonstrate its potential by operating a simple lab-on-chip to carry out the detection of dopamine using various electroanalytical methods. Full article
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Open AccessReview
Clinical Utility and Future Applications of PET/CT and PET/CMR in Cardiology
Diagnostics 2016, 6(3), 32; doi:10.3390/diagnostics6030032 -
Abstract
Over the past several years, there have been major advances in cardiovascular positron emission tomography (PET) in combination with either computed tomography (CT) or, more recently, cardiovascular magnetic resonance (CMR). These multi-modality approaches have significant potential to leverage the strengths of each modality
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Over the past several years, there have been major advances in cardiovascular positron emission tomography (PET) in combination with either computed tomography (CT) or, more recently, cardiovascular magnetic resonance (CMR). These multi-modality approaches have significant potential to leverage the strengths of each modality to improve the characterization of a variety of cardiovascular diseases and to predict clinical outcomes. This review will discuss current developments and potential future uses of PET/CT and PET/CMR for cardiovascular applications, which promise to add significant incremental benefits to the data provided by each modality alone. Full article
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Open AccessReview
Point-of-Care Diagnostics for Improving Maternal Health in South Africa
Diagnostics 2016, 6(3), 31; doi:10.3390/diagnostics6030031 -
Abstract
Improving maternal health is a global priority, particularly in high HIV-endemic, resource-limited settings. Failure to use health care facilities due to poor access is one of the main causes of maternal deaths in South Africa. “Point-of-care” (POC) diagnostics are an innovative healthcare approach
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Improving maternal health is a global priority, particularly in high HIV-endemic, resource-limited settings. Failure to use health care facilities due to poor access is one of the main causes of maternal deaths in South Africa. “Point-of-care” (POC) diagnostics are an innovative healthcare approach to improve healthcare access and health outcomes in remote and resource-limited settings. In this review, POC testing is defined as a diagnostic test that is carried out near patients and leads to rapid clinical decisions. We review the current and emerging POC diagnostics for maternal health, with a specific focus on the World Health Organization (WHO) quality-ASSURED (Affordability, Sensitivity, Specificity, User friendly, Rapid and robust, Equipment free and Delivered) criteria for an ideal point-of-care test in resource-limited settings. The performance of POC diagnostics, barriers and challenges related to implementing POC diagnostics for maternal health in rural and resource-limited settings are reviewed. Innovative strategies for overcoming these barriers are recommended to achieve substantial progress on improving maternal health outcomes in these settings. Full article
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Open AccessCommunication
18F-FET-PET in Primary Hyperparathyroidism: A Pilot Study
Diagnostics 2016, 6(3), 30; doi:10.3390/diagnostics6030030 -
Abstract
Preoperative localisation of the diseased parathyroid gland(s) in primary hyperparathyroidism (PHP) is a prerequisite for subsequent minimally invasive surgery. Recently, as alternatives to conventional sestamibi parathyroid scintigraphy, the 11C-based positron emission tomography (PET) tracers methionine and choline have shown promise for this
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Preoperative localisation of the diseased parathyroid gland(s) in primary hyperparathyroidism (PHP) is a prerequisite for subsequent minimally invasive surgery. Recently, as alternatives to conventional sestamibi parathyroid scintigraphy, the 11C-based positron emission tomography (PET) tracers methionine and choline have shown promise for this purpose. We evaluated the feasibility of using the 18F-based PET tracer fluoroethyl-l-tyrosine (FET), as the longer half-life of 18F makes it logistically more favourable. As a proof-of-concept study, we included two patients with PHP in which dual-isotope parathyroid subtraction single photon emission computed tomography had determined the exact location of the parathyroid adenoma. A dynamic FET PET/CT scan was performed with subsequent visual evaluation and calculation of target-to-background (TBR; parathyroid vs. thyroid). The maximum TBR in the two patients under study was achieved approximately 30 min after the injection of the tracer and was 1.5 and 1.7, respectively. This ratio was too small to allow for confident visualisation of the adenomas. FET PET/CT seems not feasible as a preoperative imaging modality in PHP. Full article
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Open AccessInteresting Images
Sternocostoclavicular Hyperostosis: An Ill-Recognized Disease
Diagnostics 2016, 6(3), 29; doi:10.3390/diagnostics6030029 -
Abstract
Sternocostoclavicular hyperostosis (SCCH) is an ill-recognized, rarely diagnosed disease. Today, SCCH is widely considered part of the synovitis, acne, pustulosis, hyperostosis and osteitis (SAPHO) syndrome. SCCH develops over years with intermittent attacks of pain, swelling, and reddening of the sternocostoclavicular region. The disease
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Sternocostoclavicular hyperostosis (SCCH) is an ill-recognized, rarely diagnosed disease. Today, SCCH is widely considered part of the synovitis, acne, pustulosis, hyperostosis and osteitis (SAPHO) syndrome. SCCH develops over years with intermittent attacks of pain, swelling, and reddening of the sternocostoclavicular region. The disease causes progressive hyperostosis, fusion of the sternocostoclavicular joints, and soft tissue ossification. SCCH is chronic, non-malignant, and occurs predominantly bilaterally in middle-aged women. The incidence of the disease is unknown. We present a case of isolated SCCH, where chest radiographs showed a clear development of bilateral disease over the course of more than a decade. Whole-body bone scintigraphy was performed and was suggestive of SCCH. The diagnosis was established as late as 14 years from the onset of symptoms. During this period, the patient underwent several inconclusive examinations, resulting in a delay of diagnosis and in prolonged and aggravated symptoms. With this case report, we want to draw attention to SCCH and the importance of early diagnosis of the disease. Full article
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Open AccessReview
Assessing Tumor Response to Treatment in Patients with Lung Cancer Using Dynamic Contrast-Enhanced CT
Diagnostics 2016, 6(3), 28; doi:10.3390/diagnostics6030028 -
Abstract
The aim of this study was to provide an overview of the literature available on dynamic contrast-enhanced computed tomography (DCE-CT) as a tool to evaluate treatment response in patients with lung cancer. This systematic review was compiled according to Preferred Reporting Items for
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The aim of this study was to provide an overview of the literature available on dynamic contrast-enhanced computed tomography (DCE-CT) as a tool to evaluate treatment response in patients with lung cancer. This systematic review was compiled according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Only original research articles concerning treatment response in patients with lung cancer assessed with DCE-CT were included. To assess the validity of each study we implemented Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2). The initial search yielded 651 publications, and 16 articles were included in this study. The articles were divided into groups of treatment. In studies where patients were treated with systemic chemotherapy with or without anti-angiogenic drugs, four out of the seven studies found a significant decrease in permeability after treatment. Four out of five studies that measured blood flow post anti-angiogenic treatments found that blood flow was significantly decreased. DCE-CT may be a useful tool in assessing treatment response in patients with lung cancer. It seems that particularly permeability and blood flow are important perfusion values for predicting treatment outcome. However, the heterogeneity in scan protocols, scan parameters, and time between scans makes it difficult to compare the included studies. Full article
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Open AccessReview
The Role of Proteomics in Biomarker Development for Improved Patient Diagnosis and Clinical Decision Making in Prostate Cancer
Diagnostics 2016, 6(3), 27; doi:10.3390/diagnostics6030027 -
Abstract
Prostate Cancer (PCa) is the second most commonly diagnosed cancer in men worldwide. Although increased expression of prostate-specific antigen (PSA) is an effective indicator for the recurrence of PCa, its intended use as a screening marker for PCa is of considerable controversy. Recent
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Prostate Cancer (PCa) is the second most commonly diagnosed cancer in men worldwide. Although increased expression of prostate-specific antigen (PSA) is an effective indicator for the recurrence of PCa, its intended use as a screening marker for PCa is of considerable controversy. Recent research efforts in the field of PCa biomarkers have focused on the identification of tissue and fluid-based biomarkers that would be better able to stratify those individuals diagnosed with PCa who (i) might best receive no treatment (active surveillance of the disease); (ii) would benefit from existing treatments; or (iii) those who are likely to succumb to disease recurrence and/or have aggressive disease. The growing demand for better prostate cancer biomarkers has coincided with the development of improved discovery and evaluation technologies for multiplexed measurement of proteins in bio-fluids and tissues. This review aims to (i) provide an overview of these technologies as well as describe some of the candidate PCa protein biomarkers that have been discovered using them; (ii) address some of the general limitations in the clinical evaluation and validation of protein biomarkers; and (iii) make recommendations for strategies that could be adopted to improve the successful development of protein biomarkers to deliver improvements in personalized PCa patient decision making. Full article
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Open AccessArticle
Mobile Diagnostics Based on Motion? A Close Look at Motility Patterns in the Schistosome Life Cycle
Diagnostics 2016, 6(2), 24; doi:10.3390/diagnostics6020024 -
Abstract
Imaging at high resolution and subsequent image analysis with modified mobile phones have the potential to solve problems related to microscopy-based diagnostics of parasitic infections in many endemic regions. Diagnostics using the computing power of “smartphones” is not restricted by limited expertise or
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Imaging at high resolution and subsequent image analysis with modified mobile phones have the potential to solve problems related to microscopy-based diagnostics of parasitic infections in many endemic regions. Diagnostics using the computing power of “smartphones” is not restricted by limited expertise or limitations set by visual perception of a microscopist. Thus diagnostics currently almost exclusively dependent on recognition of morphological features of pathogenic organisms could be based on additional properties, such as motility characteristics recognizable by computer vision. Of special interest are infectious larval stages and “micro swimmers” of e.g., the schistosome life cycle, which infect the intermediate and definitive hosts, respectively. The ciliated miracidium, emerges from the excreted egg upon its contact with water. This means that for diagnostics, recognition of a swimming miracidium is equivalent to recognition of an egg. The motility pattern of miracidia could be defined by computer vision and used as a diagnostic criterion. To develop motility pattern-based diagnostics of schistosomiasis using simple imaging devices, we analyzed Paramecium as a model for the schistosome miracidium. As a model for invasive nematodes, such as strongyloids and filaria, we examined a different type of motility in the apathogenic nematode Turbatrix, the “vinegar eel.” The results of motion time and frequency analysis suggest that target motility may be expressed as specific spectrograms serving as “diagnostic fingerprints.” Full article
Open AccessInteresting Images
Angiogenesis PET Tracer Uptake (68Ga-NODAGA-E[(cRGDyK)]2) in Induced Myocardial Infarction in Minipigs
Diagnostics 2016, 6(2), 26; doi:10.3390/diagnostics6020026 -
Abstract
Angiogenesis is part of the healing process following an ischemic injury and is vital for the post-ischemic repair of the myocardium. Therefore, it is of particular interest to be able to noninvasively monitor angiogenesis. This might, not only permit risk stratification of patients
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Angiogenesis is part of the healing process following an ischemic injury and is vital for the post-ischemic repair of the myocardium. Therefore, it is of particular interest to be able to noninvasively monitor angiogenesis. This might, not only permit risk stratification of patients following myocardial infarction, but could also facilitate development and improvement of new therapies directed towards stimulation of the angiogenic response. During angiogenesis endothelial cells must adhere to one another to form new microvessels. αvβ3 integrin has been found to be highly expressed in activated endothelial cells and has been identified as a critical modulator of angiogenesis. 68Ga-NODAGA-E[c(RGDyK)]2 (RGD) has recently been developed by us as an angiogenesis positron-emission-tomography (PET) ligand targeted towards αvβ3 integrin. In the present study, we induced myocardial infarction in Göttingen minipigs. Successful infarction was documented by 82Rubidium-dipyridamole stress PET and computed tomography. RGD uptake was demonstrated in the infarcted myocardium one week and one month after induction of infarction by RGD-PET. In conclusion, we demonstrated angiogenesis by noninvasive imaging using RGD-PET in minipigs hearts, which resemble human hearts. The perspectives are very intriguing and might permit the evaluation of new treatment strategies targeted towards increasing the angiogenetic response, e.g., stem-cell treatment. Full article