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Diagnostics, Volume 8, Issue 3 (September 2018) – 26 articles

Cover Story (view full-size image): The featured review in this issue of Diagnostics discusses current strategies in prostate cancer management—from diagnosis, therapy, and prognosis—while emphasizing the unmet need of stratifying patients for optimal care. Recent genomic, transcriptomic, and epigenomic analyses uncovering the spectrum of molecular heterogeneity in both localized and advanced disease, and the emergence of molecular signatures in pre-clinical and clinical settings underscore the plausibility of applying precision medicine in this cancer entity. View this paper.
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15 pages, 2292 KiB  
Article
Diagnosis of Newly Delivered Mothers for Periodontitis with a Novel Oral-Rinse aMMP-8 Point-of-Care Test in a Rural Malawian Population
by Jussi M. Leppilahti, Ulla Harjunmaa, Jorma Järnstedt, Charles Mangani, Marcela Hernández, Taina Tervahartiala, Rodrigo Lopez, Ulla Ashorn, Per Ashorn, Dirk-Rolf Gieselmann and Timo Sorsa
Diagnostics 2018, 8(3), 67; https://doi.org/10.3390/diagnostics8030067 - 15 Sep 2018
Cited by 26 | Viewed by 5202
Abstract
A novel qualitative point-of-care test of activated matrix metalloproteinase-8 (aMMP-8) using noninvasive oral rinse sampling procedures has been developed for the early detection of collagen breakdown indicating periodontal tissue destruction. The main object of this study was to assess the reliability of the [...] Read more.
A novel qualitative point-of-care test of activated matrix metalloproteinase-8 (aMMP-8) using noninvasive oral rinse sampling procedures has been developed for the early detection of collagen breakdown indicating periodontal tissue destruction. The main object of this study was to assess the reliability of the test in a low-income setting to identify participants with history of periodontal destruction detected as alveolar bone loss (ABL) in radiographs. This cross-sectional study included 486 women who had recently delivered in rural Malawi. The aMMP-8 test and dental panoramic radiographs were taken within 48 h of delivery. The performance of the test in comparison to radiological examinations was tested by following the standards for reporting of diagnostic accuracy studies protocol (STARD) with respective statistical measures and 95% confidence intervals. From the 486 eligible participants, 461 mothers with complete data, aged from 15 to 46 years (mean 24.8, SD 6.0) were included in the analysis. ABL was identified in 116 of 461 participants. There was 56% agreement between the aMMP-8 test results and detected ABL (yes or no) in radiographs. Calculated sensitivity of the test was 80% (72–87%), specificity 48% (43–54%), positive predictive value 34% (31–37%), negative predictive value 88% (83–91%), positive likelihood ratio 1.55 (1.35–1.77), and negative likelihood ratio 0.41(0.28–0.60). The aMMP-8 test sensitivity and negative predictive value to identify the ABL cases were relatively high, but there was additionally a high rate of test-positive results in participants without ABL, especially in young mothers, leading to low overall agreement between the test results and radiological bone loss. Further longitudinal studies are needed to examine if the test positive subjects are in risk of future bone loss before the detectable signs of periodontitis in radiographs. Full article
(This article belongs to the Special Issue Novel Point-of-Care Technologies in Diagnostics 2018)
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9 pages, 385 KiB  
Article
A Brief Questionnaire to Assess Post-Exertional Malaise
by Joseph Cotler, Carly Holtzman, Catherine Dudun and Leonard A. Jason
Diagnostics 2018, 8(3), 66; https://doi.org/10.3390/diagnostics8030066 - 11 Sep 2018
Cited by 75 | Viewed by 15420
Abstract
Post-exertional malaise (PEM) is a key symptom of myalgic encephalomyelitis (ME) and chronic fatigue syndrome (CFS). Currently, five PEM-items from the DePaul Symptom Questionnaire (DSQ) were recommended as a first step in measuring this symptom for patients with ME and CFS by the [...] Read more.
Post-exertional malaise (PEM) is a key symptom of myalgic encephalomyelitis (ME) and chronic fatigue syndrome (CFS). Currently, five PEM-items from the DePaul Symptom Questionnaire (DSQ) were recommended as a first step in measuring this symptom for patients with ME and CFS by the National Institutes of Health/Centers for Disease Control and Prevention (NIH/CDC) Common Data Elements’ (CDE) working group. The second step in this process, as recommended by the NIH/CDC CDE working group, involves assembling information from various sources to confirm the presence of PEM. There have not been any efforts, to date, to standardize this second-step process in the assessment of PEM. The current study examined whether five supplementary items on the DSQ could be used to operationalize the second step of the recommendations made by the NIH/CDC CDE working group. The five supplementary DSQ PEM duration items correctly categorized patients with ME or CFS 81.7% of the time, while incorrectly categorizing multiple sclerosis (MS) and post-polio syndrome (PPS) as ME or CFS only 16.6% of the time. The findings suggested that a PEM second-step process could be operationalized using supplementary DSQ items. Full article
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10 pages, 590 KiB  
Article
Hypertension Assessment via ECG and PPG Signals: An Evaluation Using MIMIC Database
by Yongbo Liang, Zhencheng Chen, Rabab Ward and Mohamed Elgendi
Diagnostics 2018, 8(3), 65; https://doi.org/10.3390/diagnostics8030065 - 10 Sep 2018
Cited by 91 | Viewed by 15182
Abstract
Cardiovascular diseases (CVDs) have become the biggest threat to human health, and they are accelerated by hypertension. The best way to avoid the many complications of CVDs is to manage and prevent hypertension at an early stage. However, there are no symptoms at [...] Read more.
Cardiovascular diseases (CVDs) have become the biggest threat to human health, and they are accelerated by hypertension. The best way to avoid the many complications of CVDs is to manage and prevent hypertension at an early stage. However, there are no symptoms at all for most types of hypertension, especially for prehypertension. The awareness and control rates of hypertension are extremely low. In this study, a novel hypertension management method based on arterial wave propagation theory and photoplethysmography (PPG) morphological theory was researched to explore the physiological changes in different blood pressure (BP) levels. Pulse Arrival Time (PAT) and photoplethysmogram (PPG) features were extracted from electrocardiogram (ECG) and PPG signals to represent the arterial wave propagation theory and PPG morphological theory, respectively. Three feature sets, one containing PAT only, one containing PPG features only, and one containing both PAT and PPG features, were used to classify the different BP categories, defined as normotension, prehypertension, and hypertension. PPG features were shown to classify BP categories more accurately than PAT. Furthermore, PAT and PPG combined features improved the BP classification performance. The F1 scores to classify normotension versus prehypertension reached 84.34%, the scores for normotension versus hypertension reached 94.84%, and the scores for normotension plus prehypertension versus hypertension reached 88.49%. This indicates that the simultaneous collection of ECG and PPG signals could detect hypertension. Full article
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11 pages, 880 KiB  
Hypothesis
Myalgic Encephalomyelitis (ME) or What? An Operational Definition
by Frank Twisk
Diagnostics 2018, 8(3), 64; https://doi.org/10.3390/diagnostics8030064 - 08 Sep 2018
Cited by 9 | Viewed by 13681
Abstract
Myalgic encephalomyelitis (ME), identified as a new clinical entity with distinctive features in 1956, was originally considered as a neuromuscular disease. In 1988 the Centers for Disease Control and Prevention introduced the ill-defined concept of chronic fatigue syndrome (CFS). As predicted, CFS, unjustly [...] Read more.
Myalgic encephalomyelitis (ME), identified as a new clinical entity with distinctive features in 1956, was originally considered as a neuromuscular disease. In 1988 the Centers for Disease Control and Prevention introduced the ill-defined concept of chronic fatigue syndrome (CFS). As predicted, CFS, unjustly considered to be a synonym for ME, pushed ME to the background. To develop effective therapies for of ME and CFS, it is essential to investigate patients with ME specifically. For that reason, an operational definition of ME is indispensable. This article proposes an operational definition based on the most recent formal definitions and symptoms observed in ME. ME is a multi-systemic illness, which (1) often has a sudden onset, in most cases a respiratory and/or gastro-intestinal infection, but a gradual or more dramatic onset is also possible; (2) has an epidemic and an endemic form; (3) has an unique clinical pattern deviating from other post-viral states; (4) is distinguished by muscle fatigability/prolonged muscle weakness after trivial exertion; (5) is accompanied by symptoms relating to neurological disturbance, especially of cognitive, autonomic, and sensory functions; (6) can be accompanied by symptoms associated with cardiac and other systems; (7) is characterized by fluctuation of symptoms (within and between “episodes”); (8) has a prolonged relapsing course; and (9) has a tendency to become chronic. In conclusion, a discriminative definition for ME contains four mandatory elements: (1) muscle fatigability/post-exertional muscle weakness lasting for days; (2) operational criteria for “neurological disturbance, especially of cognitive, autonomic and sensory functions”; (3) fluctuation of symptoms; and (4) a prolonged relapsing course. This tentative definition of ME justifies the qualification “neuromuscular disease”. Full article
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15 pages, 1249 KiB  
Review
Circulating Tumor Cells for the Management of Renal Cell Carcinoma
by Lucile Broncy and Patrizia Paterlini-Bréchot
Diagnostics 2018, 8(3), 63; https://doi.org/10.3390/diagnostics8030063 - 03 Sep 2018
Cited by 11 | Viewed by 6463
Abstract
Renal cell carcinoma is a highly malignant cancer that would benefit from non-invasive innovative markers providing early diagnosis and recurrence detection. Circulating tumor cells are a particularly promising marker of tumor invasion that could be used to improve the management of patients with [...] Read more.
Renal cell carcinoma is a highly malignant cancer that would benefit from non-invasive innovative markers providing early diagnosis and recurrence detection. Circulating tumor cells are a particularly promising marker of tumor invasion that could be used to improve the management of patients with RCC. However, the extensive genetic and immunophenotypic heterogeneity of cells from RCC and their trend to transition to the mesenchymal phenotype when they circulate in blood constitute a challenge for their sensitive and specific detection. This review analyzes published studies targeting CTC in patients with RCC, in the context of the biological, pathological, and molecular complexity of this particular cancer. Although further analytical and clinical studies are needed to pinpoint the most suitable approach for highly sensitive CTC detection in RCC patients, it is clear that this field can bring a relevant guide to clinicians and help to RCC patients. Furthermore, as described, a particular subtype of RCC—the ccRCC—can be used as a model to study the relationship between cytomorphological and genetic cellular markers of malignancy, an important issue for the study of CTC from any type of solid cancer. Full article
(This article belongs to the Special Issue Circulating Tumor Cells as Cancer Diagnostic Biomarkers)
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26 pages, 1054 KiB  
Review
Genome-Based Classification and Therapy of Prostate Cancer
by Arlou Kristina Angeles, Simone Bauer, Leonie Ratz, Sabine M. Klauck and Holger Sültmann
Diagnostics 2018, 8(3), 62; https://doi.org/10.3390/diagnostics8030062 - 02 Sep 2018
Cited by 17 | Viewed by 8355
Abstract
In the past decade, multi-national and multi-center efforts were launched to sequence prostate cancer genomes, transcriptomes, and epigenomes with the aim of discovering the molecular underpinnings of tumorigenesis, cancer progression, and therapy resistance. Multiple biological markers and pathways have been discovered to be [...] Read more.
In the past decade, multi-national and multi-center efforts were launched to sequence prostate cancer genomes, transcriptomes, and epigenomes with the aim of discovering the molecular underpinnings of tumorigenesis, cancer progression, and therapy resistance. Multiple biological markers and pathways have been discovered to be tumor drivers, and a molecular classification of prostate cancer is emerging. Here, we highlight crucial findings of these genome-sequencing projects in localized and advanced disease. We recapitulate the utility and limitations of current clinical practices to diagnosis, prognosis, and therapy, and we provide examples of insights generated by the molecular profiling of tumors. Novel treatment concepts based on these molecular alterations are currently being addressed in clinical trials and will lead to an enhanced implementation of precision medicine strategies. Full article
(This article belongs to the Special Issue Diagnostic Biomarkers in Prostate Cancer)
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18 pages, 7061 KiB  
Article
Effects of the Plastic of the Realistic GeePS-L2S-Breast Phantom
by Tomas Rydholm, Andreas Fhager, Mikael Persson, Shireen D. Geimer and Paul M. Meaney
Diagnostics 2018, 8(3), 61; https://doi.org/10.3390/diagnostics8030061 - 01 Sep 2018
Cited by 22 | Viewed by 4700
Abstract
A breast phantom developed at the Supelec Institute was interrogated to study its suitability for microwave tomography measurements. A microwave measurement system based on 16 monopole antennas and a vector network analyzer was used to study how the S-parameters are influenced by insertion [...] Read more.
A breast phantom developed at the Supelec Institute was interrogated to study its suitability for microwave tomography measurements. A microwave measurement system based on 16 monopole antennas and a vector network analyzer was used to study how the S-parameters are influenced by insertion of the phantom. The phantom is a 3D-printed structure consisting of plastic shells that can be filled with tissue mimicking liquids. The phantom was filled with different liquids and tested with the measurement system to determine whether the plastic has any effects on the recovered images or not. Measurements of the phantom when it is filled with the same liquid as the surrounding coupling medium are of particular interest. In this case, the phantom plastic has a substantial effects on the measurements which ultimately detracts from the desired images. Full article
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27 pages, 563 KiB  
Review
RNAs as Candidate Diagnostic and Prognostic Markers of Prostate Cancer—From Cell Line Models to Liquid Biopsies
by Marvin C. J. Lim, Anne-Marie Baird, John Aird, John Greene, Dhruv Kapoor, Steven G. Gray, Ray McDermott and Stephen P. Finn
Diagnostics 2018, 8(3), 60; https://doi.org/10.3390/diagnostics8030060 - 30 Aug 2018
Cited by 17 | Viewed by 6535
Abstract
The treatment landscape of prostate cancer has evolved rapidly over the past five years. The explosion in treatment advances has been witnessed in parallel with significant progress in the field of molecular biomarkers. The advent of next-generation sequencing has enabled the molecular profiling [...] Read more.
The treatment landscape of prostate cancer has evolved rapidly over the past five years. The explosion in treatment advances has been witnessed in parallel with significant progress in the field of molecular biomarkers. The advent of next-generation sequencing has enabled the molecular profiling of the genomic and transcriptomic architecture of prostate and other cancers. Coupled with this, is a renewed interest in the role of non-coding RNA (ncRNA) in prostate cancer biology. ncRNA consists of several different classes including small non-coding RNA (sncRNA), long non-coding RNA (lncRNA), and circular RNA (circRNA). These families are under active investigation, given their essential roles in cancer initiation, development and progression. This review focuses on the evidence for the role of RNAs in prostate cancer, and their use as diagnostic and prognostic markers, and targets for treatment in this disease. Full article
(This article belongs to the Special Issue Diagnostic Biomarkers in Prostate Cancer)
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46 pages, 1905 KiB  
Review
The Interplay between Circulating Tumor Cells and the Immune System: From Immune Escape to Cancer Immunotherapy
by Kevin Leone, Cristina Poggiana and Rita Zamarchi
Diagnostics 2018, 8(3), 59; https://doi.org/10.3390/diagnostics8030059 - 30 Aug 2018
Cited by 51 | Viewed by 9492
Abstract
Circulating tumor cells (CTCs) have aroused increasing interest not only in mechanistic studies of metastasis, but also for translational applications, such as patient monitoring, treatment choice, and treatment change due to tumor resistance. In this review, we will assess the state of the [...] Read more.
Circulating tumor cells (CTCs) have aroused increasing interest not only in mechanistic studies of metastasis, but also for translational applications, such as patient monitoring, treatment choice, and treatment change due to tumor resistance. In this review, we will assess the state of the art about the study of the interactions between CTCs and the immune system. We intend to analyze the impact that the cells of the immune system have in limiting or promoting the metastatic capability of CTCs. To this purpose, we will examine studies that correlate CTCs, immune cells, and patient prognosis, and we will also discuss relevant animal models that have contributed to the understanding of the mechanisms of immune-mediated metastasis. We will then consider some studies in which CTCs seem to play a promising role in monitoring cancer patients during immunotherapy regimens. We believe that, from an accurate and profound knowledge of the interactions between CTCs and the immune system, new immunotherapeutic strategies against cancer might emerge in the future. Full article
(This article belongs to the Special Issue Circulating Tumor Cells as Cancer Diagnostic Biomarkers)
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7 pages, 472 KiB  
Communication
Triplex Real-Time PCR without DNA Extraction for the Monitoring of Meningococcal Disease
by Melissa J. Whaley, Laurel T. Jenkins, Fang Hu, Alexander Chen, Seydou Diarra, Rasmata Ouédraogo-Traoré, Claudio T. Sacchi and Xin Wang
Diagnostics 2018, 8(3), 58; https://doi.org/10.3390/diagnostics8030058 - 30 Aug 2018
Cited by 4 | Viewed by 4176
Abstract
Detection of Neisseria meningitidis has become less time- and resource-intensive with a monoplex direct real-time PCR (drt-PCR) to amplify genes from clinical specimens without DNA extraction. To further improve efficiency, we evaluated two triplex drt-PCR assays for the detection of meningococcal serogroups AWX [...] Read more.
Detection of Neisseria meningitidis has become less time- and resource-intensive with a monoplex direct real-time PCR (drt-PCR) to amplify genes from clinical specimens without DNA extraction. To further improve efficiency, we evaluated two triplex drt-PCR assays for the detection of meningococcal serogroups AWX and BCY. The sensitivity and specificity of the triplex assays were assessed using 228 cerebrospinal fluid (CSF) specimens from meningitis patients and compared to the monoplex for six serogroups. The lower limit of detection range for six serogroup-specific drt-PCR assays was 178–5264 CFU/mL by monoplex and 68–2221 CFU/mL by triplex. The triplex and monoplex showed 100% agreement for six serogroups and the triplex assays achieved similar sensitivity and specificity estimates as the monoplex drt-PCR assays. Our triplex method reduces the time and cost of processing CSF specimens by characterizing six serogroups with only two assays, which is particularly important for testing large numbers of specimens for N. meningitidis surveillance. Full article
(This article belongs to the Special Issue Diagnosis of Bacterial Pathogens)
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27 pages, 1435 KiB  
Review
Promise and Implementation of Proteomic Prostate Cancer Biomarkers
by Agnieszka Latosinska, Maria Frantzi, Axel S. Merseburger and Harald Mischak
Diagnostics 2018, 8(3), 57; https://doi.org/10.3390/diagnostics8030057 - 29 Aug 2018
Cited by 11 | Viewed by 5618
Abstract
Prostate cancer is one of the most commonly diagnosed malignancy and the fifth leading cause of cancer mortality in men. Despite the broad use of prostate-specific antigen test that resulted in an increase in number of diagnosed cases, disease management needs to be [...] Read more.
Prostate cancer is one of the most commonly diagnosed malignancy and the fifth leading cause of cancer mortality in men. Despite the broad use of prostate-specific antigen test that resulted in an increase in number of diagnosed cases, disease management needs to be improved. Proteomic biomarkers alone and or in combination with clinical and pathological risk calculators are expected to improve on decreasing the unnecessary biopsies, stratify low risk patients, and predict response to treatment. To this end, significant efforts have been undertaken to identify novel biomarkers that can accurately discriminate between indolent and aggressive cancer forms and indicate those men at high risk for developing prostate cancer that require immediate treatment. In the era of “big data” and “personalized medicine” proteomics-based biomarkers hold great promise to provide clinically applicable tools, as proteins regulate all biological functions, and integrate genomic information with the environmental impact. In this review article, we aim to provide a critical assessment of the current proteomics-based biomarkers for prostate cancer and their actual clinical applicability. For that purpose, a systematic review of the literature published within the last 10 years was performed using the Web of Science Database. We specifically discuss the potential and prospects of use for diagnostic, prognostic and predictive proteomics-based biomarkers, including both body fluid- and tissue-based markers. Full article
(This article belongs to the Special Issue Diagnostic Biomarkers in Prostate Cancer)
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18 pages, 2273 KiB  
Article
Computer Aided Classification of Neuroblastoma Histological Images Using Scale Invariant Feature Transform with Feature Encoding
by Soheila Gheisari, Daniel R. Catchpoole, Amanda Charlton, Zsombor Melegh, Elise Gradhand and Paul J. Kennedy
Diagnostics 2018, 8(3), 56; https://doi.org/10.3390/diagnostics8030056 - 28 Aug 2018
Cited by 10 | Viewed by 6515
Abstract
Neuroblastoma is the most common extracranial solid malignancy in early childhood. Optimal management of neuroblastoma depends on many factors, including histopathological classification. Although histopathology study is considered the gold standard for classification of neuroblastoma histological images, computers can help to extract many more [...] Read more.
Neuroblastoma is the most common extracranial solid malignancy in early childhood. Optimal management of neuroblastoma depends on many factors, including histopathological classification. Although histopathology study is considered the gold standard for classification of neuroblastoma histological images, computers can help to extract many more features some of which may not be recognizable by human eyes. This paper, proposes a combination of Scale Invariant Feature Transform with feature encoding algorithm to extract highly discriminative features. Then, distinctive image features are classified by Support Vector Machine classifier into five clinically relevant classes. The advantage of our model is extracting features which are more robust to scale variation compared to the Patched Completed Local Binary Pattern and Completed Local Binary Pattern methods. We gathered a database of 1043 histologic images of neuroblastic tumours classified into five subtypes. Our approach identified features that outperformed the state-of-the-art on both our neuroblastoma dataset and a benchmark breast cancer dataset. Our method shows promise for classification of neuroblastoma histological images. Full article
(This article belongs to the Special Issue Computer-Aided Diagnosis and Characterization of Diseases)
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15 pages, 3345 KiB  
Article
A Preliminary Study of Contrast-Enhanced Ultrasound (CEUS) and Cytokine Expression Analysis (CEA) as Early Predictors for the Outcome of Tibial Non-Union Therapy
by Patrick Haubruck, Raban Heller, Michael C. Tanner, Volker Daniel, Gerhard Schmidmaier, Farhoud Bolourchi, Arash Moghaddam and Christian Fischer
Diagnostics 2018, 8(3), 55; https://doi.org/10.3390/diagnostics8030055 - 24 Aug 2018
Cited by 7 | Viewed by 4711
Abstract
The current study investigates if contrast-enhanced ultrasound (CEUS) or cytokine expression analysis (CEA) evaluating vascularization are capable of predicting the outcome of non-union therapy. Patients with tibial non-unions were surgically treated and participated in our follow-up program including perioperative collection of blood as [...] Read more.
The current study investigates if contrast-enhanced ultrasound (CEUS) or cytokine expression analysis (CEA) evaluating vascularization are capable of predicting the outcome of non-union therapy. Patients with tibial non-unions were surgically treated and participated in our follow-up program including perioperative collection of blood as well as CEUS analysis. Two groups were formed: Responders in group 1 (G1, N = 8) and Non-Responders in group 2 (G2, N = 5). Serum cytokine expression and local microperfusion were compared and correlated to the radiologic outcome. Evaluation of TNF-α expression revealed significantly lower values prior to first surgery in G1 (G1: 9.66 ± 0.96 pg/mL versus G2: 12.63 ± 1.2 pg/mL; p = 0.045); whereas after treatment both CEA and CEUS indicated a higher potential for angiogenesis in Responders. Logistic regression modelling revealed the highest predictive power regarding eventual osseous consolidation for the combination of both CEUS and serum CEA. The results provide first evidence regarding a link between changes in the serum expression of distinct pro-angiogenic cytokines and alterations in the local microperfusion assessed via both non-invasive and radiation-free diagnostic modalities. In addition, a combination of CEUS and CEA is a promising novel tool in early prediction of the outcome of non-union therapy. Full article
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8 pages, 35122 KiB  
Article
Comparison of X-ray-Mammography and Planar UWB Microwave Imaging of the Breast: First Results from a Patient Study
by Dennis Wörtge, Jochen Moll, Viktor Krozer, Babak Bazrafshan, Frank Hübner, Clara Park and Thomas J. Vogl
Diagnostics 2018, 8(3), 54; https://doi.org/10.3390/diagnostics8030054 - 21 Aug 2018
Cited by 24 | Viewed by 4921
Abstract
Hemispherical and cylindrical antenna arrays are widely used in radar-based and tomography-based microwave breast imaging systems. Based on the dielectric contrast between healthy and malignant tissue, a three-dimensional image could be formed to locate the tumor. However, conventional X-ray mammography as the golden [...] Read more.
Hemispherical and cylindrical antenna arrays are widely used in radar-based and tomography-based microwave breast imaging systems. Based on the dielectric contrast between healthy and malignant tissue, a three-dimensional image could be formed to locate the tumor. However, conventional X-ray mammography as the golden standard in breast cancer screening produces two-dimensional breast images so that a comparison between the 3D microwave image and the 2D mammogram could be difficult. In this paper, we present the design and realisation of a UWB breast imaging prototype for the frequency band from 1 to 9 GHz. We present a refined system design in light of the clinical usage by means of a planar scanning and compare microwave images with those obtained by X-ray mammography. Microwave transmission measurements were processed to create a two-dimensional image of the breast that can be compared directly with a two-dimensional mammogram. Preliminary results from a patient study are presented and discussed showing the ability of the proposed system to locate the tumor. Full article
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38 pages, 14559 KiB  
Article
On-Site Validation of a Microwave Breast Imaging System, before First Patient Study
by Angie Fasoula, Luc Duchesne, Julio Daniel Gil Cano, Peter Lawrence, Guillaume Robin and Jean-Gael Bernard
Diagnostics 2018, 8(3), 53; https://doi.org/10.3390/diagnostics8030053 - 18 Aug 2018
Cited by 45 | Viewed by 6223
Abstract
This paper presents the Wavelia microwave breast imaging system that has been recently installed at the Galway University Hospital, Ireland, for a first-in-human pilot clinical test. Microwave breast imaging has been extensively investigated over the last two decades as an alternative imaging modality [...] Read more.
This paper presents the Wavelia microwave breast imaging system that has been recently installed at the Galway University Hospital, Ireland, for a first-in-human pilot clinical test. Microwave breast imaging has been extensively investigated over the last two decades as an alternative imaging modality that could potentially bring complementary information to state-of-the-art modalities such as X-ray mammography. Following an overview of the main working principles of this technology, the Wavelia imaging system architecture is presented, as are the radar signal processing algorithms that are used in forming the microwave images in which small tumors could be detectable for disease diagnosis. The methodology and specific quality metrics that have been developed to properly evaluate and validate the performance of the imaging system using complex breast phantoms that are scanned at controlled measurement conditions are also presented in the paper. Indicative results from the application of this methodology to the on-site validation of the imaging system after its installation at the hospital for pilot clinical testing are thoroughly presented and discussed. Given that the imaging system is still at the prototype level of development, a rigorous quality assessment and system validation at nominal operating conditions is very important in order to ensure high-quality clinical data collection. Full article
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15 pages, 1808 KiB  
Article
Impact of Information Loss on Reconstruction Quality in Microwave Tomography for Medical Imaging
by Zhenzhuang Miao, Panagiotis Kosmas and Syed Ahsan
Diagnostics 2018, 8(3), 52; https://doi.org/10.3390/diagnostics8030052 - 14 Aug 2018
Cited by 15 | Viewed by 5158
Abstract
This paper studies how limited information in data acquired by a wideband microwave tomography (MWT) system can affect the quality of reconstructed images. Limitations can arise from experimental errors, mismatch between the system and its model in the imaging algorithm, or losses in [...] Read more.
This paper studies how limited information in data acquired by a wideband microwave tomography (MWT) system can affect the quality of reconstructed images. Limitations can arise from experimental errors, mismatch between the system and its model in the imaging algorithm, or losses in the immersion and coupling medium which are required to moderate this mismatch. We also present a strategy for improving reconstruction performance by discarding data that is dominated by experimental errors. The approach relies on recording transmitted signals in a wide frequency range, and then correlating the data in different frequencies. We apply this method to our wideband MWT prototype, which has been developed in our previous work. Using this system, we present results from simulated and experimental data which demonstrate the practical value of the frequency selection approach. We also propose a K-neighbour method to identify low quality data in a robust manner. The resulting enhancement in imaging quality suggests that this approach can be useful for various medical imaging scenarios, provided that data from multiple frequencies can be acquired and used in the reconstruction process. Full article
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14 pages, 2579 KiB  
Article
Evaluating Functional Connectivity Alterations in Autism Spectrum Disorder Using Network-Based Statistics
by Aitana Pascual-Belda, Antonio Díaz-Parra and David Moratal
Diagnostics 2018, 8(3), 51; https://doi.org/10.3390/diagnostics8030051 - 07 Aug 2018
Cited by 16 | Viewed by 6615
Abstract
The study of resting-state functional brain networks is a powerful tool to understand the neurological bases of a variety of disorders such as Autism Spectrum Disorder (ASD). In this work, we have studied the differences in functional brain connectivity between a group of [...] Read more.
The study of resting-state functional brain networks is a powerful tool to understand the neurological bases of a variety of disorders such as Autism Spectrum Disorder (ASD). In this work, we have studied the differences in functional brain connectivity between a group of 74 ASD subjects and a group of 82 typical-development (TD) subjects using functional magnetic resonance imaging (fMRI). We have used a network approach whereby the brain is divided into discrete regions or nodes that interact with each other through connections or edges. Functional brain networks were estimated using the Pearson’s correlation coefficient and compared by means of the Network-Based Statistic (NBS) method. The obtained results reveal a combination of both overconnectivity and underconnectivity, with the presence of networks in which the connectivity levels differ significantly between ASD and TD groups. The alterations mainly affect the temporal and frontal lobe, as well as the limbic system, especially those regions related with social interaction and emotion management functions. These results are concordant with the clinical profile of the disorder and can contribute to the elucidation of its neurological basis, encouraging the development of new clinical approaches. Full article
(This article belongs to the Special Issue Brain Imaging)
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7 pages, 5374 KiB  
Article
A Novel Technique for Intraoral Ultrasound-Guided Aspiration of Peritonsillar Abscess
by Tobias Todsen, Mads Georg Stage and Christoffer Holst Hahn
Diagnostics 2018, 8(3), 50; https://doi.org/10.3390/diagnostics8030050 - 02 Aug 2018
Cited by 10 | Viewed by 9714
Abstract
Peritonsillar abscess (PTA) is a common complication to acute tonsillitis. The treatment is drainage of the abscess, but many needle aspirations are unsuccessful due to a low diagnostic accuracy based on oral examination only. In this article, we describe how intraoral ultrasound can [...] Read more.
Peritonsillar abscess (PTA) is a common complication to acute tonsillitis. The treatment is drainage of the abscess, but many needle aspirations are unsuccessful due to a low diagnostic accuracy based on oral examination only. In this article, we describe how intraoral ultrasound can be added to improve the diagnostic work-up of PTA and present a novel technique for ultrasound-guided aspiration of PTA, using a small pencil-shaped transducer. We present our first clinical experiences with this technique and describe how it could be integrated in a clinical setting to guide safe and successful needle aspirations of PTA. Full article
(This article belongs to the Special Issue Novel Point-of-Care Technologies in Diagnostics 2018)
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15 pages, 915 KiB  
Article
Quantitative Analysis of Seven New Prostate Cancer Biomarkers and the Potential Future of the ‘Biomarker Laboratory’
by Kevin Cao, Callum Arthurs, Ali Atta-ul, Michael Millar, Mariana Beltran, Jochen Neuhaus, Lars-Christian Horn, Rui Henrique, Aamir Ahmed and Christopher Thrasivoulou
Diagnostics 2018, 8(3), 49; https://doi.org/10.3390/diagnostics8030049 - 27 Jul 2018
Cited by 8 | Viewed by 6271
Abstract
Prostate cancer is the third highest cause of male mortality in the developed world, with the burden of the disease increasing dramatically with demographic change. There are significant limitations to the current diagnostic regimens and no established effective screening modality. To this end, [...] Read more.
Prostate cancer is the third highest cause of male mortality in the developed world, with the burden of the disease increasing dramatically with demographic change. There are significant limitations to the current diagnostic regimens and no established effective screening modality. To this end, research has discovered hundreds of potential ‘biomarkers’ that may one day be of use in screening, diagnosis or prognostication. However, the barriers to bringing biomarkers to clinical evaluation and eventually into clinical usage have yet to be realised. This is an operational challenge that requires some new thinking and development of paradigms to increase the efficiency of the laboratory process and add ‘value’ to the clinician. Value comes in various forms, whether it be a process that is seamlessly integrated into the hospital laboratory environment or one that can provide additional ‘information’ for the clinical pathologist in terms of risk profiling. We describe, herein, an efficient and tissue-conserving pipeline that uses Tissue Microarrays in a semi-automated process that could, one day, be integrated into the hospital laboratory domain, using seven putative prostate cancer biomarkers for illustration. Full article
(This article belongs to the Special Issue Diagnostic Biomarkers in Prostate Cancer)
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9 pages, 2096 KiB  
Article
Computer-Aided Diagnosis Scheme for Determining Histological Classification of Breast Lesions on Ultrasonographic Images Using Convolutional Neural Network
by Akiyoshi Hizukuri and Ryohei Nakayama
Diagnostics 2018, 8(3), 48; https://doi.org/10.3390/diagnostics8030048 - 25 Jul 2018
Cited by 9 | Viewed by 5577
Abstract
It can be difficult for clinicians to accurately discriminate among histological classifications of breast lesions on ultrasonographic images. The purpose of this study was to develop a computer-aided diagnosis (CADx) scheme for determining histological classifications of breast lesions using a convolutional neural network [...] Read more.
It can be difficult for clinicians to accurately discriminate among histological classifications of breast lesions on ultrasonographic images. The purpose of this study was to develop a computer-aided diagnosis (CADx) scheme for determining histological classifications of breast lesions using a convolutional neural network (CNN). Our database consisted of 578 breast ultrasonographic images. It included 287 malignant (217 invasive carcinomas and 70 noninvasive carcinomas) and 291 benign lesions (111 cysts and 180 fibroadenomas). In this study, the CNN constructed from four convolutional layers, three batch-normalization layers, four pooling layers, and two fully connected layers was employed for distinguishing between the four different types of histological classifications for lesions. The classification accuracies for histological classifications with our CNN model were 83.9–87.6%, which were substantially higher than those with our previous method (55.7–79.3%) using hand-crafted features and a classifier. The area under the curve with our CNN model was 0.976, whereas that with our previous method was 0.939 (p = 0.0001). Our CNN model would be useful in differential diagnoses of breast lesions as a diagnostic aid. Full article
(This article belongs to the Special Issue Computer-Aided Diagnosis and Characterization of Diseases)
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14 pages, 2678 KiB  
Article
ALTEA: A Software Tool for the Evaluation of New Biomarkers for Alzheimer’s Disease by Means of Textures Analysis on Magnetic Resonance Images
by Carlos López-Gómez, Rafael Ortiz-Ramón, Enrique Mollá-Olmos, David Moratal and For the Alzheimer’s Disease Neuroimaging Initiative
Diagnostics 2018, 8(3), 47; https://doi.org/10.3390/diagnostics8030047 - 19 Jul 2018
Cited by 7 | Viewed by 6481
Abstract
The current criteria for diagnosing Alzheimer’s disease (AD) require the presence of relevant cognitive deficits, so the underlying neuropathological damage is important by the time the diagnosis is made. Therefore, the evaluation of new biomarkers to detect AD in its early stages has [...] Read more.
The current criteria for diagnosing Alzheimer’s disease (AD) require the presence of relevant cognitive deficits, so the underlying neuropathological damage is important by the time the diagnosis is made. Therefore, the evaluation of new biomarkers to detect AD in its early stages has become one of the main research focuses. The purpose of the present study was to evaluate a set of texture parameters as potential biomarkers of the disease. To this end, the ALTEA (ALzheimer TExture Analyzer) software tool was created to perform 2D and 3D texture analysis on magnetic resonance images. This intuitive tool was used to analyze textures of circular and spherical regions situated in the right and left hippocampi of a cohort of 105 patients: 35 AD patients, 35 patients with early mild cognitive impairment (EMCI) and 35 cognitively normal (CN) subjects. A total of 25 statistical texture parameters derived from the histogram, the Gray-Level Co-occurrence Matrix and the Gray-Level Run-Length Matrix, were extracted from each region and analyzed statistically to study their predictive capacity. Several textural parameters were statistically significant (p < 0.05) when differentiating AD subjects from CN and EMCI patients, which indicates that texture analysis could help to identify the presence of AD. Full article
(This article belongs to the Special Issue Brain Imaging)
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9 pages, 628 KiB  
Article
The Frequency of Focal Thyroid Incidental Findings and Risk of Malignancy Detected by 18F-Fluorodeoxyglucose Positron Emission Tomography in an Iodine Deficient Population
by Nina Gedberg, Jesper Karmisholt, Michael Gade, Rune V. Fisker, Victor Iyer and Lars J. Petersen
Diagnostics 2018, 8(3), 46; https://doi.org/10.3390/diagnostics8030046 - 17 Jul 2018
Cited by 8 | Viewed by 4313
Abstract
Incidental focal uptake of 18F-fluorodeoxyglucose (FDG) in the thyroid on positron emission tomography (PET/CT) is rare but often associated with malignancy. The epidemiology of thyroid incidentalomas has only to some extent been described in countries with iodine deficiency. Here we report data from [...] Read more.
Incidental focal uptake of 18F-fluorodeoxyglucose (FDG) in the thyroid on positron emission tomography (PET/CT) is rare but often associated with malignancy. The epidemiology of thyroid incidentalomas has only to some extent been described in countries with iodine deficiency. Here we report data from Denmark, a country with known iodine deficiency and wide access to PET/CT. All FDG PET/CT comprising the head and neck region, during 2014, were retrospectively reviewed, and patients with focal FDG uptake in the thyroid gland were identified. A total of 2451 patients had an FDG PET/CT of which 59 (2.4%) patients presented with FDG-avid focal lesions in the thyroid gland. Among the 59 patients with FDG-avid lesions, 33 patients (56%) received work up with ultrasound, thyroid technetium scintigraphy, fine needle aspiration, and/or histology of which 20 patients had a conclusive pathology report. Ten patients with FDG-avid lesions were identified with thyroid malignancy. The risk of thyroid malignancy was 16.9% among patient with incidental FDG-avid thyroid lesions. Our findings indicated a similar frequency of FDG thyroid incidentalomas and malignancy rates in an iodine deficient population compared to summary data from prior studies, studies mostly performed in geographical areas of normal or excess iodine supplementation. Full article
(This article belongs to the Special Issue New Diagnostic and Therapeutic Approach of Thyroid Diseases)
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11 pages, 1441 KiB  
Review
Whole-Body MRI with Diffusion-Weighted Imaging in Bone Metastases: A Narrative Review
by Alessandro Stecco, Alessandra Trisoglio, Eleonora Soligo, Sara Berardo, Lidiia Sukhovei and Alessandro Carriero
Diagnostics 2018, 8(3), 45; https://doi.org/10.3390/diagnostics8030045 - 09 Jul 2018
Cited by 47 | Viewed by 9644
Abstract
Whole body magnetic resonance imaging (MRI) with diffusion-weighted imaging (WB-MRI-DWI) is currently emerging as a diagnostic technique in the evaluation of bone metastases from breast, prostate, lung, thyroid, and melanoma tumors. The most relevant articles regarding the detection of solid tumor bone metastases [...] Read more.
Whole body magnetic resonance imaging (MRI) with diffusion-weighted imaging (WB-MRI-DWI) is currently emerging as a diagnostic technique in the evaluation of bone metastases from breast, prostate, lung, thyroid, and melanoma tumors. The most relevant articles regarding the detection of solid tumor bone metastases with MRI have been reviewed and cited. The imaging methods currently used in the detection of bone metastases are bone scintigraphy, computed tomography (CT), and positron emission tomography (PET/CT) with 2-deoxy-2-[fluorine-18] fluoro-d-glucose (18F-FDG PET/CT). WB-MRI-DWI allows qualitative and quantitative evaluation of focal lesions through signal intensity evaluation on DWI images and the reconstruction of the apparent diffusion coefficient (ADC) map. In prostate and breast cancer, WB-MRI-DWI is useful in assessing the response of bone lesions to therapy and to detecting early non-responders, while in lung cancer the method shows a similar sensitivity to 18F-FDG PET/CT in the detection of bone metastases. In bone metastases of thyroid tumors and melanoma, the WB-MRI-DWI shows a higher sensitivity when compared to 18F-FDG PET/CT. With a standardization of the WB-MRI-DWI protocol, this method seems to play an important role in the diagnosis of bone solid tumor metastases. Full article
(This article belongs to the Special Issue Imaging of Bone Metastases in Oncology)
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11 pages, 223 KiB  
Article
Utility of Two-Dimensional Difference Gel Electrophoresis in Diagnosis of Multiple Sclerosis
by Michael Auer, Harald Hegen, Dagmar Rudzki, Georg Golderer and Florian Deisenhammer
Diagnostics 2018, 8(3), 44; https://doi.org/10.3390/diagnostics8030044 - 05 Jul 2018
Cited by 2 | Viewed by 5006
Abstract
Two-dimensional difference gel electrophoresis (2D-DIGE) has been used for identification of possible biomarkers in the cerebrospinal fluid (CSF) of multiple sclerosis (MS) patients. However, in different studies inconsistent results have been obtained. We wanted to analyze the diagnostic value of 2D-DIGE in early [...] Read more.
Two-dimensional difference gel electrophoresis (2D-DIGE) has been used for identification of possible biomarkers in the cerebrospinal fluid (CSF) of multiple sclerosis (MS) patients. However, in different studies inconsistent results have been obtained. We wanted to analyze the diagnostic value of 2D-DIGE in early MS patients by comparing protein patterns between single and pooled samples of MS patients and controls. CSF samples of 20 MS patients and 10 control subjects were processed with 2D-DIGE. The so obtained protein patterns were analyzed with DeCyder 6.5 software, whereby we described variation of patterns presented in one gel as well as between different gels. Even when running single samples of patients of the same group in one gel, variation of protein patterns was high. The number of identified spots with different protein level varied between 4 and 30, depending on which sample batches were compared. We did not find a consistent pattern throughout all possible batch combinations. The inter-individual variation of protein expression as well as the susceptibility of 2D-DIGE for methodological variations makes use of 2D-DIGE as a diagnostic tool for MS and for detection of possible candidate biomarkers difficult, since detected proteins vary depending on which samples are compared. Full article
(This article belongs to the Collection Biomarkers in Medicine)
10 pages, 2057 KiB  
Article
Evaluation of 2D Imaging Schemes for Pulsed Arterial Spin Labeling of the Human Kidney Cortex
by Charlotte E. Buchanan, Eleanor F. Cox and Susan T. Francis
Diagnostics 2018, 8(3), 43; https://doi.org/10.3390/diagnostics8030043 - 28 Jun 2018
Cited by 9 | Viewed by 4928
Abstract
A number of imaging readout schemes are proposed for renal arterial spin labeling (ASL) to quantify kidney cortex perfusion, including gradient echo-based methods of balanced fast field echo (bFFE) and gradient-echo echo-planar imaging (GE-EPI), or spin echo-based schemes of spin-echo echo-planar imaging (SE-EPI) [...] Read more.
A number of imaging readout schemes are proposed for renal arterial spin labeling (ASL) to quantify kidney cortex perfusion, including gradient echo-based methods of balanced fast field echo (bFFE) and gradient-echo echo-planar imaging (GE-EPI), or spin echo-based schemes of spin-echo echo-planar imaging (SE-EPI) and turbo spin-echo (TSE). Here, we compare these two-dimensional (2D) imaging schemes to evaluate the optimal imaging scheme for pulsed ASL (PASL) assessment of human kidney cortex perfusion at 3 T. Ten healthy volunteers with normal renal function were scanned using each 2D multi-slice imaging scheme, in combination with a respiratory triggered flow-sensitive alternating inversion recovery (FAIR) ASL scheme on a 3 T Philips Achieva scanner. All volunteers returned for a second identical scan session within two weeks of the first scan session. Comparisons were made between the imaging schemes in terms of perfusion-weighted image (PWI) signal-to-noise ratio (SNR) and perfusion quantification, temporal SNR (tSNR), spatial coverage, and repeatability. For each imaging scheme, the renal cortex perfusion was calculated (bFFE: 276 ± 29 mL/100g/min, GE-EPI: 222 ± 18 mL/100g/min, SE-EPI: 201 ± 36 mL/100g/min, and TSE: 200 ± 20 mL/100g/min). Perfusion was found to be higher for GE-based readouts when compared with SE-based readouts, with significantly higher measured perfusion for the bFFE readout when compared with all other schemes (p < 0.05), attributed to the greater vascular signal present. Despite the PWI-SNR being significantly lower for SE-EPI when compared with all other schemes (p < 0.05), the SE-EPI readout gave the highest tSNR, and was found to be the most reproducible scheme for the assessment of kidney cortex, with a coefficient of variation (CoV) of 17.2%, whilst minimizing variability of the perfusion-weighted signal across slices for whole-kidney perfusion assessment. For the assessment of kidney cortex perfusion using 2D readout schemes, SE-EPI provides optimal tSNR, minimal variability across slices, and repeatable data acquired in a short scan time with low specific absorption rate. Full article
(This article belongs to the Special Issue Functional and Molecular Imaging of Kidney and Urogenital Disease)
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24 pages, 868 KiB  
Review
Neural Indicators of Fatigue in Chronic Diseases: A Systematic Review of MRI Studies
by María Goñi, Neil Basu, Alison D. Murray and Gordon D. Waiter
Diagnostics 2018, 8(3), 42; https://doi.org/10.3390/diagnostics8030042 - 21 Jun 2018
Cited by 20 | Viewed by 6782
Abstract
While fatigue is prevalent in chronic diseases, the neural mechanisms underlying this symptom remain unknown. Magnetic resonance imaging (MRI) has the potential to enable us to characterize this symptom. The aim of this review was to gather and appraise the current literature on [...] Read more.
While fatigue is prevalent in chronic diseases, the neural mechanisms underlying this symptom remain unknown. Magnetic resonance imaging (MRI) has the potential to enable us to characterize this symptom. The aim of this review was to gather and appraise the current literature on MRI studies of fatigue in chronic diseases. We systematically searched the following databases: MedLine, PsycInfo, Embase and Scopus (inception to April 2016). We selected studies according to a predefined inclusion and exclusion criteria. We assessed the quality of the studies and conducted descriptive statistical analyses. We identified 26 studies of varying design and quality. Structural and functional MRI, alongside diffusion tensor imaging (DTI) and functional connectivity (FC) studies, identified significant brain indicators of fatigue. The most common regions were the frontal lobe, parietal lobe, limbic system and basal ganglia. Longitudinal studies offered more precise and reliable analysis. Brain structures found to be related to fatigue were highly heterogeneous, not only between diseases, but also for different studies of the same disease. Given the different designs, methodologies and variable results, we conclude that there are currently no well-defined brain indicators of fatigue in chronic diseases. Full article
(This article belongs to the Section Medical Imaging and Theranostics)
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