Publications by authors named "Georgios Z Papadakis"

75 Publications

Advanced clinical imaging for the evaluation of stem cell based therapies.

Expert Opin Biol Ther 2021 Feb 23:1-12. Epub 2021 Feb 23.

Department of Medical Imaging, University Hospital of Heraklion, Crete, Greece.

: As stem cell treatments reach closer to the clinic, the need for appropriate noninvasive imaging for accurate disease diagnosis, treatment planning, follow-up, and early detection of complications, is constantly rising. Clinical radiology affords an extensive arsenal of advanced imaging techniques, to provide anatomical and functional information on the whole spectrum of stem cell treatments from diagnosis to follow-up.: This manuscript aims at providing a critical review of major published studies on the utilization of advanced imaging for stem cell treatments. Uses of magnetic resonance imaging (MRI), computed tomography (CT), ultrasound, and positron emission tomography (PET) are reviewed and interrogated for their applicability to stem cell imaging.: A wide spectrum of imaging methods have been utilized for the evaluation of stem cell therapies. The majority of published techniques are not clinically applicable, using methods exclusively applicable to animals or technology irrelevant to current clinical practice. Harmonization of preclinical methods with clinical reality is necessary for the timely translation of stem cell therapies to the clinic. Methods such as diffusion weighted MRI, hybrid imaging, and contrast-enhanced ultrasound hold great promise and should be routinely incorporated in the evaluation of patients receiving stem cell treatments.
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http://dx.doi.org/10.1080/14712598.2021.1890711DOI Listing
February 2021

Extended perfusion protocol for MS lesion quantification.

Open Med (Wars) 2020 8;15(1):520-530. Epub 2020 Jun 8.

Foundation for Research and Technology - Hellas, Institute of Computer Science, Computational Bio-Medicine Laboratory, N. Plastira 100, Vassilika Vouton, GR-700 13 Heraklion, Crete, Greece.

This study aims to examine a time-extended dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) protocol and report a comparative study with three different pharmacokinetic (PK) models, for accurate determination of subtle blood-brain barrier (BBB) disruption in patients with multiple sclerosis (MS). This time-extended DCE-MRI perfusion protocol, called Snaps, was applied on 24 active demyelinating lesions of 12 MS patients. Statistical analysis was performed for both protocols through three different PK models. The Snaps protocol achieved triple the window time of perfusion observation by extending the magnetic resonance acquisition time by less than 2 min on average for all patients. In addition, the statistical analysis in terms of adj- goodness of fit demonstrated that the Snaps protocol outperformed the conventional DCE-MRI protocol by detecting 49% more pixels on average. The exclusive pixels identified from the Snaps protocol lie in the low range, potentially reflecting areas with subtle BBB disruption. Finally, the extended Tofts model was found to have the highest fitting accuracy for both analyzed protocols. The previously proposed time-extended DCE protocol, called Snaps, provides additional temporal perfusion information at the expense of a minimal extension of the conventional DCE acquisition time.
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http://dx.doi.org/10.1515/med-2020-0100DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7711864PMC
June 2020

Volumetric Modeling of Adrenal Gland Size in Primary Bilateral Macronodular Adrenocortical Hyperplasia.

J Endocr Soc 2021 Jan 29;5(1):bvaa162. Epub 2020 Oct 29.

Section on Endocrinology & Genetics (SEGEN), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Bethesda, MD, USA.

Context: Radiological characterization of adrenal size in primary bilateral macronodular adrenocortical hyperplasia (PBMAH) has not been previously investigated.

Objective: We hypothesized that volumetric modeling of adrenal gland size may correlate with biochemical disease severity in patients with PBMAH. Secondary analysis of patients with concurrent primary aldosteronism (PA) was performed.

Design: A retrospective cross-sectional analysis of 44 patients with PBMAH was conducted from 2000 to 2019.

Setting: Tertiary care clinical research center.

Patients: Patients were diagnosed with PBMAH based upon clinical, genetic, radiographic and biochemical characteristics.

Intervention: Clinical, biochemical, and genetic data were obtained. Computed tomography scans were used to create volumetric models by manually contouring both adrenal glands in each slice using Vitrea Core Fx v6.3 software (Vital Images, Minnetonka, Minnesota).

Main Outcome And Measures: 17-hydroxycorticosteroids (17-OHS), genetics, and aldosterone-to-renin ratio (ARR) were retrospectively obtained. Pearson test was used for correlation analysis of biochemical data with adrenal volume.

Results: A cohort of 44 patients with PBMAH was evaluated, with a mean age (±SD) of 53 ± 11.53. Eight patients met the diagnostic criteria for PA, of whom 6 (75%) were Black. In the Black cohort, total adrenal volumes positively correlated with midnight cortisol (R = 0.76,  = 0.028), urinary free cortisol (R = 0.70,  = 0.035), and 17-OHS (R = 0.87,  = 0.0045), with a more pronounced correlation with left adrenal volume alone. 17-OHS concentration positively correlated with total, left, and right adrenal volume in patients harboring pathogenic variants in (R = 0.72,  = 0.018; R = 0.65,  = 0.042; and R = 0.73,  = 0.016, respectively).

Conclusions: Volumetric modeling of adrenal gland size may associate with biochemical severity in patients with PBMAH, with particular utility in Black patients.
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http://dx.doi.org/10.1210/jendso/bvaa162DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7716656PMC
January 2021

Prevalence of Hypothyroidism in Patients With Erdheim-Chester Disease.

JAMA Netw Open 2020 10 1;3(10):e2019169. Epub 2020 Oct 1.

Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland.

Importance: Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis affecting multiple organs and commonly caused by somatic pathogenic variants in BRAF V600E and mitogen-activated protein kinase genes. Clinical features of ECD result from histiocytic involvement of various tissues; while endocrine involvement in ECD occurs frequently, the prevalence of central or primary hypothyroidism has not been thoroughly investigated.

Objective: To assess hypothalamus-pituitary-thyroid (HPT) dysfunction in patients with ECD.

Design, Setting, And Participants: This cross-sectional study included 61 patients with ECD who were enrolled in a natural history study at a tertiary care center between January 2011 and December 2018. ECD was diagnosed on the basis of clinical, genetic, and histopathological features. Data were analyzed in March 2020.

Exposure: Diagnosis of ECD.

Main Outcomes And Measures: Main outcome was the prevalence of thyroid dysfunction in adults with ECD compared with community estimates. Patients underwent baseline evaluation with a thyroid function test, including thyrotropin, free thyroxine (fT4), and total thyroxine (T4), and sellar imaging with magnetic resonance imaging or computed tomography scan. The association of HPT dysfunction was assessed for differences in age, sex, body mass index, BRAF V600E status, high sensitivity C-reactive protein level, sellar imaging, and pituitary hormonal dysfunction.

Results: A total of 61 patients with ECD (46 [75%] men; mean [SD] age, 54.3 [10.9] years) were evaluated. Seventeen patients (28%) had hypothyroidism requiring levothyroxine therapy. The prevalence of both central and primary hypothyroidism were higher than community estimates (central hypothyroidism: 9.8% vs 0.1%; odds ratio, 109.0; 95% CI, 37.4-260.6; P < .001; primary hypothyroidism: 18.0% vs 4.7%; OR, 4.4; 95% CI, 2.1-8.7; P < .001). Patients with hypothyroidism (both primary and central), compared with patients with euthyroidism, had higher body mass index (median [interquartile range] 31.4 [28.3-38.3] vs 26.7 [24.4-31.9]; P = .004) and a higher prevalence of panhypopituitarism (7 [47%] vs 3 [7%]; P < .001). Among patients with hypothyroidism, those with central hypothyroidism, compared with patients with primary hypothyroidism, had a lower mean (SD) body mass index (28.3 [2.6] vs 36.3 [5.9]; P = .007) and higher frequencies of abnormal sellar imaging (5 [83%] vs 3 [27%]; P = .050) and panhypopituitarism (5 [83%] vs 3 [27%]; P = .050).

Conclusions And Relevance: In this cohort study, a higher prevalence of central and primary hypothyroidism was identified in patients with ECD compared with the community. There should be a low threshold for testing for hypothyroidism in patients with ECD, and treatment should follow standard guidelines.
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http://dx.doi.org/10.1001/jamanetworkopen.2020.19169DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7596581PMC
October 2020

Diffusion Tensor Imaging and Chemical Exchange Saturation Transfer MRI Evaluation on the Long-Term Effects of Pulsed Focused Ultrasound and Microbubbles Blood Brain Barrier Opening in the Rat.

Front Neurosci 2020 25;14:908. Epub 2020 Aug 25.

Frank Laboratory, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health (NIH), Bethesda, MD, United States.

Blood-brain barrier opening (BBBO) with pulsed Focused Ultrasound (pFUS) and microbubbles (MB) has received increasing interest as a method for neurotherapeutics of the central nervous system. In general, conventional MRI [i.e., T2w, T2w, gadolinium (Gd) enhanced T1w] is used to monitor the effects of pFUS+MB on BBBO and/or assess whether sonication results in parenchymal damage. This study employed multimodal MRI techniques and F-Fludeoxyglucose (FDG) PET to evaluate the effects of single and multiple weekly pFUS+MB sessions on morphology and glucose utilization levels in the rat cortex and hippocampus. pFUS was performed with 0.548 MHz transducer with a slow infusion over 1 min of Optison (5-8 × 10 MB) in nine focal points in cortex and four in hippocampus. During pFUS+MB treatment, Gd-T1w was performed at 3 T to confirm BBBO, along with subsequent T2w, T2w, DTI and glucose CEST (glucoCEST)-weighted imaging by high field 9.4 T and compared with FDG-PET and immunohistochemistry. Animals receiving a single pFUS+MB exhibited minimal hypointense voxels on T2w. Brains receiving multiple pFUS+MB treatments demonstrated persistent T2w and T2 abnormalities associated with changes in DTI and glucoCEST when compared to contralateral parenchyma. Decreased glucoCEST contrast was substantiated by FDG-PET in cortex following multiple sonications. Immunohistochemistry showed significantly dilated vessels and decreased neuronal glucose transporter (GLUT3) expression in sonicated cortex and hippocampus without changes in neuronal counts. These results suggest the importance to standardize MRI protocols in concert with advanced imaging techniques when evaluating long term effects of pFUS+MB BBBO in clinical trials for neurological diseases.
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http://dx.doi.org/10.3389/fnins.2020.00908DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7478124PMC
August 2020

Musculoskeletal trauma imaging in the era of novel molecular methods and artificial intelligence.

Injury 2020 Dec 16;51(12):2748-2756. Epub 2020 Sep 16.

Department of Medical Imaging, Heraklion University Hospital, Crete, 70110, Greece; Advanced Hybrid Imaging Systems, Institute of Computer Science, Foundation for Research and Technology (FORTH), N. Plastira 100, Vassilika Vouton 70013, Heraklion, Crete, Greece; Computational Biomedicine Laboratory (CBML), Foundation for Research and Technology Hellas (FORTH), 70013, Heraklion, Crete, Greece; Department of Radiology, School of Medicine, University of Crete, 70110 Greece. Electronic address:

Over the past decade rapid advancements in molecular imaging (MI) and artificial intelligence (AI) have revolutionized traditional musculoskeletal radiology. Molecular imaging refers to the ability of various methods to in vivo characterize and quantify biological processes, at a molecular level. The extracted information provides the tools to understand the pathophysiology of diseases and thus to early detect, to accurately evaluate the extend and to apply and evaluate targeted treatments. At present, molecular imaging mainly involves CT, MRI, radionuclide, US, and optical imaging and has been reported in many clinical and preclinical studies. Although originally MI techniques targeted at central nervous system disorders, later on their value on musculoskeletal disorders was also studied in depth. Meaningful exploitation of the large volume of imaging data generated by molecular and conventional imaging techniques, requires state-of-the-art computational methods that enable rapid handling of large volumes of information. AI allows end-to-end training of computer algorithms to perform tasks encountered in everyday clinical practice including diagnosis, disease severity classification and image optimization. Notably, the development of deep learning algorithms has offered novel methods that enable intelligent processing of large imaging datasets in an attempt to automate decision-making in a wide variety of settings related to musculoskeletal trauma. Current applications of AI include the diagnosis of bone and soft tissue injuries, monitoring of the healing process and prediction of injuries in the professional sports setting. This review presents the current applications of novel MI techniques and methods and the emerging role of AI regarding the diagnosis and evaluation of musculoskeletal trauma.
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http://dx.doi.org/10.1016/j.injury.2020.09.019DOI Listing
December 2020

Advancing COVID-19 differentiation with a robust preprocessing and integration of multi-institutional open-repository computer tomography datasets for deep learning analysis.

Exp Ther Med 2020 Nov 11;20(5):78. Epub 2020 Sep 11.

Computational Biomedicine Laboratory (CBML), Foundation for Research and Technology Hellas (FORTH), 70013 Heraklion, Greece.

The coronavirus pandemic and its unprecedented consequences globally has spurred the interest of the artificial intelligence research community. A plethora of published studies have investigated the role of imaging such as chest X-rays and computer tomography in coronavirus disease 2019 (COVID-19) automated diagnosis. Οpen repositories of medical imaging data can play a significant role by promoting cooperation among institutes in a world-wide scale. However, they may induce limitations related to variable data quality and intrinsic differences due to the wide variety of scanner vendors and imaging parameters. In this study, a state-of-the-art custom U-Net model is presented with a dice similarity coefficient performance of 99.6% along with a transfer learning VGG-19 based model for COVID-19 versus pneumonia differentiation exhibiting an area under curve of 96.1%. The above was significantly improved over the baseline model trained with no segmentation in selected tomographic slices of the same dataset. The presented study highlights the importance of a robust preprocessing protocol for image analysis within a heterogeneous imaging dataset and assesses the potential diagnostic value of the presented COVID-19 model by comparing its performance to the state of the art.
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http://dx.doi.org/10.3892/etm.2020.9210DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7500043PMC
November 2020

CD271 stem cell treatment of patients with chronic stroke.

Exp Ther Med 2020 Sep 26;20(3):2055-2062. Epub 2020 Jun 26.

CI Parhon Institute of Endocrinology, 011863 Bucharest, Romania.

Patients with chronic stroke have currently little hope for motor improvement towards regaining independent activities of daily living; stem cell treatments offer a new treatment option and needs to be developed. Patients with chronic stroke (more than 3 months prior to stem cell treatment, mean 21.2 months post-stroke) were treated with CD271 stem cells, 7 patients received autologous and 1 allogeneic cells from first degree relative; administration was intravenous in 1 and intrathecal in 7 patients. Each patient received a single treatment consisting of 2-5x10 cells/kg and they were followed up for up to 12 months. There were significant improvements in expressive aphasia (2/3 patients) spasticity (5/5, of which 2 were transient), and small improvements in motor function (2/8 patients). Although motor improvements were minor in our chronic stroke patients, improvements in aphasia and spasticity were significant and in the context of good safety we are advocating further administration and clinical studies of CD271 stem cells not only in chronic stroke patients, but also for spastic paresis/plegia; a different, yet unexplored application is pulmonary emphysema.
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http://dx.doi.org/10.3892/etm.2020.8948DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7401309PMC
September 2020

Targeting vulnerable atherosclerotic plaque via PET-tracers aiming at cell-surface overexpression of somatostatin receptors.

Biomed Rep 2020 Sep 16;13(3). Epub 2020 Jun 16.

Department of Radiology, Medical School, University of Crete, 71003 Heraklion, Greece.

Cardiovascular disease (CD) is the leading cause of death in the developed world, with major atherothrombotic events, being mainly attributed to the rupture of unstable, vulnerable atherosclerotic lesions, leading to blood flow obstruction. Since unstable atherosclerotic plaques frequently do not cause hemodynamically significant blood flow restriction, conventional stress imaging tests cannot depict the vulnerable, high-risk for rupture atherosclerotic lesions. Therefore, molecular imaging techniques targeting specific pathophysiologic features related to atherosclerotic plaque rupture mechanism, hold promise for precise and individualized treatment strategies of CD. In the current report, we describe in a patient diagnosed with pancreatic neuroendocrine tumor, the selective uptake of Ga-DOATATE by an atherosclerotic lesion in the thoracic aorta. This data indicates that Ga-DOTATATE, which is a positron emitting tomography tracer, targeting the recruitment of macrophages taking place in the vulnerable plaque, could potentially serve as an imaging probe for the detection of high-risk, prone to rupture plaques.
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http://dx.doi.org/10.3892/br.2020.1316DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7391298PMC
September 2020

Interpretable artificial intelligence framework for COVID-19 screening on chest X-rays.

Exp Ther Med 2020 Aug 27;20(2):727-735. Epub 2020 May 27.

Computational Biomedicine Laboratory (CBML), Foundation for Research and Technology Hellas (FORTH), 70013 Heraklion, Greece.

COVID-19 has led to an unprecedented healthcare crisis with millions of infected people across the globe often pushing infrastructures, healthcare workers and entire economies beyond their limits. The scarcity of testing kits, even in developed countries, has led to extensive research efforts towards alternative solutions with high sensitivity. Chest radiological imaging paired with artificial intelligence (AI) can offer significant advantages in diagnosis of novel coronavirus infected patients. To this end, transfer learning techniques are used for overcoming the limitations emanating from the lack of relevant big datasets, enabling specialized models to converge on limited data, as in the case of X-rays of COVID-19 patients. In this study, we present an interpretable AI framework assessed by expert radiologists on the basis on how well the attention maps focus on the diagnostically-relevant image regions. The proposed transfer learning methodology achieves an overall area under the curve of 1 for a binary classification problem across a 5-fold training/testing dataset.
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http://dx.doi.org/10.3892/etm.2020.8797DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7388253PMC
August 2020

A dissection of SARS‑CoV2 with clinical implications (Review).

Int J Mol Med 2020 Aug 10;46(2):489-508. Epub 2020 Jun 10.

Department of Analytical and Forensic Medical Toxicology, Sechenov University, 119991 Moscow, Russia.

We are being confronted with the most consequential pandemic since the Spanish flu of 1918‑1920 to the extent that never before have 4 billion people quarantined simultaneously; to address this global challenge we bring to the forefront the options for medical treatment and summarize SARS‑CoV2 structure and functions, immune responses and known treatments. Based on literature and our own experience we propose new interventions, including the use of amiodarone, simvastatin, pioglitazone and curcumin. In mild infections (sore throat, cough) we advocate prompt local treatment for the naso‑pharynx (inhalations; aerosols; nebulizers); for moderate to severe infections we propose a tried‑and‑true treatment: the combination of arginine and ascorbate, administered orally or intravenously. The material is organized in three sections: i) Clinical aspects of COVID‑19; acute respiratory distress syndrome (ARDS); known treatments; ii) Structure and functions of SARS‑CoV2 and proposed antiviral drugs; iii) The combination of arginine‑ascorbate.
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http://dx.doi.org/10.3892/ijmm.2020.4636DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7307812PMC
August 2020

Artificial intelligence radiogenomics for advancing precision and effectiveness in oncologic care (Review).

Int J Oncol 2020 Jul 11;57(1):43-53. Epub 2020 May 11.

Computational Biomedicine Laboratory (CBML), Foundation for Research and Technology Hellas (FORTH), 70013 Heraklion, Greece.

The new era of artificial intelligence (AI) has introduced revolutionary data‑driven analysis paradigms that have led to significant advancements in information processing techniques in the context of clinical decision‑support systems. These advances have created unprecedented momentum in computational medical imaging applications and have given rise to new precision medicine research areas. Radiogenomics is a novel research field focusing on establishing associations between radiological features and genomic or molecular expression in order to shed light on the underlying disease mechanisms and enhance diagnostic procedures towards personalized medicine. The aim of the current review was to elucidate recent advances in radiogenomics research, focusing on deep learning with emphasis on radiology and oncology applications. The main deep learning radiogenomics architectures, together with the clinical questions addressed, and the achieved genetic or molecular correlations are presented, while a performance comparison of the proposed methodologies is conducted. Finally, current limitations, potentially understudied topics and future research directions are discussed.
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http://dx.doi.org/10.3892/ijo.2020.5063DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7252460PMC
July 2020

Complementary role of F-FDG and Ga-DOTATATE PET/CT in the surveillance of patients with von Hippel-Lindau syndrome.

Ann Gastroenterol 2020 May-Jun;33(3):323. Epub 2020 Mar 14.

Positron Emission Tomography (PET) Department, Clinical Center (CC), National Institutes of Health (NIH), Bethesda, Maryland, USA (Corina Millo).

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http://dx.doi.org/10.20524/aog.2020.0465DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7196616PMC
March 2020

PET/CT and PET/MRI in ophthalmic oncology (Review).

Int J Oncol 2020 Feb 3;56(2):417-429. Epub 2020 Jan 3.

Department of Radiology, Medical School, University of Crete, 71003 Heraklion, Greece.

Orbital and ocular anatomy is quite complex, consisting of several tissues, which can give rise to both benign and malignant tumors, while several primary neoplasms can metastasize to the orbital and ocular space. Early detection, accurate staging and re‑staging, efficient monitoring of treatment response, non‑invasive differentiation between benign and malignant lesions, and accurate planning of external radiation treatment, are of utmost importance for the optimal and individualized management of ophthalmic oncology patients. Addressing these challenges requires the employment of several diagnostic imaging techniques, such as high‑definition digital fundus photography, ultrasound imaging, optical coherence tomography, optical coherence tomography (OCT)‑angiography, computed tomography (CT) and magnetic resonance imaging (MRI). In recent years, technological advances have enabled the development of hybrid positron emission tomography (PET)/CT and PET/MRI systems, setting new standards in cancer diagnosis and treatment. The capability of simultaneously targeting several cancer‑related biochemical procedures using positron emitting‑radiopharmaceuticals, while morphologically characterizing lesions by CT or MRI, together with the intrinsic quantitative capabilities of PET‑imaging, provide incremental diagnostic information, enabling accurate, highly efficient and personalized treatment strategies. Aim of the current review is to discuss the current applications of hybrid PET/CT and PET/MRI imaging in the management of patients presenting with the most commonly encountered orbital and ocular tumors.
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http://dx.doi.org/10.3892/ijo.2020.4955DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6959466PMC
February 2020

Computerized Analysis of Brain MRI Parameter Dynamics in Young Patients With Cushing Syndrome-A Case-Control Study.

J Clin Endocrinol Metab 2020 05;105(5)

Section on Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland.

Background: Young patients with Cushing Syndrome (CS) may develop cognitive and behavioral alterations during disease course.

Methods: To investigate the effects of CS on the brain, we analyzed consecutive MRI scans of patients with (n = 29) versus without CS (n = 8). Multiple brain compartments were processed for total and gray/white matter (GM/WM) volumes and intensities, and cortical volume, thickness, and surface area. Dynamics (last/baseline scans ratio per parameter) were analyzed versus cortisol levels and CS status (persistent, resolved, and non-CS).

Results: Twenty-four-hour urinary free cortisol (24hUFC) measurements had inverse correlation with the intensity of subcortical GM structures and of the corpus callosum, and with the cerebral WM intensity. 24hUFC dynamics had negative correlation with volume dynamics of multiple cerebral and cerebellar structures. Patients with persistent CS had less of an increase in cortical thickness and WM intensity, and less of a decrease in WM volume compared with patients with resolution of CS. Patients with resolution of their CS had less of an increase in subcortical GM and cerebral WM volumes, but a greater increase in cortical thickness of frontal lobe versus controls.

Conclusion: Changes in WM/GM consistency, intensity, and homogeneity in patients with CS may correlate with CS clinical consequences better than volume dynamics alone.
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http://dx.doi.org/10.1210/clinem/dgz303DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7089850PMC
May 2020

Adrenocortical carcinoma and pulmonary embolism from tumoral extension.

Endocrinol Diabetes Metab Case Rep 2019 Nov 25;2019. Epub 2019 Nov 25.

Section on Endocrinology & Genetics, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA.

Summary: Adrenococortical carcinoma (ACC) is a rare cancer, occurring at the rate of one case in two million person years. Cushing syndrome or a mixed picture of excess androgen and glucocorticoid production are the most common presentations of ACC. Other uncommon presentations include abdominal pain and adrenal incidentalomas. In the present report, a 71-year-old male presented with abdominal pain and was eventually diagnosed with ACC. He was found to have pulmonary thromboembolism following an investigation for hypoxemia, with the tumor thrombus extending upto the right atrium. This interesting case represents the unique presentation of a rare tumor, which if detected late or left untreated is associated with poor outcomes, highlighting the need for a low index of suspicion for ACC when similar presentations are encountered in clinical practice.

Learning Points: ACC is a rare but aggressive tumor. ACC commonly presents with rapid onset of hypercortisolism, combined hyperandrogenism and hypercortisolism, or uncommonly with compressive symptoms. Clinicians should have a low index of suspicion for ACC in patients presenting with rapid onset of symptoms related to hypercortisolism and/or hyperandrogenism. Venous thromboembolism and extension of the tumor thrombus to the right side of the heart is a very rare but serious complication of ACC that clinicans should be wary of. The increased risk of venous thromboembolism in ACC could be explained by direct tumor invasion, tumor thrombi or hypercoagulability secondary to hypercortisolism. Early diagnosis and prompt treatment can improve the long-term survival of patients with ACC.
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http://dx.doi.org/10.1530/EDM-19-0095DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6893304PMC
November 2019

A novel deep learning architecture outperforming 'off‑the‑shelf' transfer learning and feature‑based methods in the automated assessment of mammographic breast density.

Oncol Rep 2019 Nov 12;42(5):2009-2015. Epub 2019 Sep 12.

Computational BioMedicine Laboratory (CBML), Institute of Computer Science (ICS), Foundation for Research and Technology‑Hellas (FORTH), 70013 Heraklion, Greece.

Potentially suspicious breast neoplasms could be masked by high tissue density, thus increasing the probability of a false‑negative diagnosis. Furthermore, differentiating breast tissue type enables patient pre‑screening stratification and risk assessment. In this study, we propose and evaluate advanced machine learning methodologies aiming at an objective and reliable method for breast density scoring from routine mammographic images. The proposed image analysis pipeline incorporates texture [Gabor filters and local binary pattern (LBP)] and gradient‑based features [histogram of oriented gradients (HOG) as well as speeded‑up robust features (SURF)]. Additionally, transfer learning approaches with ImageNet trained weights were also used for comparison, as well as a convolutional neural network (CNN). The proposed CNN model was fully trained on two open mammography datasets and was found to be the optimal performing methodology (AUC up to 87.3%). Thus, the findings of this study indicate that automated density scoring in mammograms can aid clinical diagnosis by introducing artificial intelligence‑powered decision‑support systems and contribute to the 'democratization' of healthcare by overcoming limitations, such as the geographic location of patients or the lack of expert radiologists.
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http://dx.doi.org/10.3892/or.2019.7312DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6787954PMC
November 2019

In vivo imaging of sterile microglial activation in rat brain after disrupting the blood-brain barrier with pulsed focused ultrasound: [18F]DPA-714 PET study.

J Neuroinflammation 2019 Jul 25;16(1):155. Epub 2019 Jul 25.

Hammoud Laboratory, Center for Infectious Disease Imaging, Clinical Center, National Institutes of Health, 10 Center Drive, Building 10, Room 1C-368, Bethesda, MD, 20892, USA.

Background: Magnetic resonance imaging (MRI)-guided pulsed focused ultrasound combined with the infusion of microbubbles (pFUS+MB) induces transient blood-brain barrier opening (BBBO) in targeted regions. pFUS+MB, through the facilitation of neurotherapeutics' delivery, has been advocated as an adjuvant treatment for neurodegenerative diseases and malignancies. Sterile neuroinflammation has been recently described following pFUS+MB BBBO. In this study, we used PET imaging with [18F]-DPA714, a biomarker of translocator protein (TSPO), to assess for neuroinflammatory changes following single and multiple pFUS+MB sessions.

Methods: Three groups of Sprague-Dawley female rats received MRI-guided pFUS+MB (Optison™; 5-8 × 10 MB/rat) treatments to the left frontal cortex and right hippocampus. Group A rats were sonicated once. Group B rats were sonicated twice and group C rats were sonicated six times on weekly basis. Passive cavitation detection feedback (PCD) controlled the peak negative pressure during sonication. We performed T1-weighted scans immediately after sonication to assess efficiency of BBBO and T2*-weighted scans to evaluate for hypointense voxels. [18F]DPA-714 PET/CT scans were acquired after the BBB had closed, 24 h after sonication in group A and within an average of 10 days from the last sonication in groups B and C. Ratios of T1 enhancement, T2* values, and [18F]DPA-714 percent injected dose/cc (%ID/cc) values in the targeted areas to the contralateral brain were calculated. Histological assessment for microglial activation/astrocytosis was performed.

Results: In all groups, [18F]DPA-714 binding was increased at the sonicated compared to non-sonicated brain (%ID/cc ratios > 1). Immunohistopathology showed increased staining for microglial and astrocytic markers in the sonicated frontal cortex compared to contralateral brain and to a lesser extent in the sonicated hippocampus. Using MRI, we documented BBB disruption immediately after sonication with resolution of BBBO 24 h later. We found more T2* hypointense voxels with increasing number of sonications. In a longitudinal group of animals imaged after two and after six sonications, there was no cumulative increase of neuroinflammation on PET.

Conclusion: Using [18F]DPA-714 PET, we documented in vivo neuroinflammatory changes in association with pFUS+MB. Our protocol (utilizing PCD feedback to minimize damage) resulted in neuroinflammation visualized 24 h post one sonication. Our findings were supported by immunohistochemistry showing microglial activation and astrocytosis. Experimental sonication parameters intended for BBB disruption should be evaluated for neuroinflammatory sequelae prior to implementation in clinical trials.
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http://dx.doi.org/10.1186/s12974-019-1543-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6657093PMC
July 2019

Treatment for benign thyroid nodules with a combination of natural extracts.

Mol Med Rep 2019 Sep 1;20(3):2332-2338. Epub 2019 Jul 1.

Department of Thyroid Pathology, National Institute of Endocrinology CI Parhon, 011863 Bucharest, Romania.

Benign thyroid nodules are among the most common endocrine disorders. Recent advances in diagnostic imaging and pathology have significantly contributed to better risk stratification of thyroid nodules. However, current treatment options, beyond surgical approaches are limited. The following placebo-controlled study presents, to the best of our knowledge, the first results of a non-invasive therapy for benign thyroid nodules. The efficacy and safety of a supplement containing spirulina, curcumin and Boswellia in euthyroid patients with benign thyroid nodules, was assessed by a 3 month, double-blind, placebo-controlled study which was completed by 34 patients. Patients with benign (FNAB documented) single thyroid nodules between 2 and 5 cm were evaluated in a prospective placebo-controlled cross-over trial, across 12 weeks (3 visits with six-week intervals). At each visit, the target thyroid nodule was recorded in two dimensions. In addition, plasma levels of thyroid stimulating hormone, free thyroxine and copper were assessed. The mean initial nodule area at V1 was 4.38±3.14 cm2, at V2 3.87±2.79 cm2, and at V3 3.53±2.84 cm2; P<0.04. Administration of the active substances (n=34) was followed by a mean area decrease of 0.611 cm2±0.933 (SD), while placebo administration (n=29) was followed by a mean decrease of 0.178 cm2±0.515 (SD), (P=0.027). The presented findings suggest that the combination of spirulina-curcumin-Βoswellia is effective in reducing the size of benign thyroid nodules. However, additional studies are needed in order to elucidate the exact mechanisms through which the suggested supplement facilitates a decrease in the size of benign thyroid nodules.
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http://dx.doi.org/10.3892/mmr.2019.10453DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6691239PMC
September 2019

F-NaF PET/CT IMAGING IN FIBROUS DYSPLASIA OF BONE.

J Bone Miner Res 2019 09 22;34(9):1619-1631. Epub 2019 May 22.

Skeletal Disorders and Mineral Homeostasis Section, National Institute of Dental and Craniofacial Research (NIDCR), National Institutes of Health, Bethesda, MD, USA.

Fibrous dysplasia (FD) is a mosaic skeletal disorder resulting in fractures, deformity, and functional impairment. Clinical evaluation has been limited by a lack of surrogate endpoints capable of quantitating disease activity. The purpose of this study was to investigate the utility of F-NaF PET/CT imaging in quantifying disease activity in patients with FD. Fifteen consecutively evaluated subjects underwent whole-body F-NaF PET/CT scans, and FD burden was assessed by quantifying FD-related F-NaF activity. F-NaF PET/CT parameters obtained included (i) SUV (standardized uptake value [SUV] of the FD lesion with the highest uptake); (ii) SUV (average SUV of all F-NaF-positive FD lesions); (iii) total volume of all F-NaF-positive FD lesions (TV); and (iv) total FD lesion activity determined as the product of TV multiplied by SUV (TA =  TV ×  SUV ) (TA). Skeletal outcomes, functional outcomes, and bone turnover markers were correlated with F-NaF PET/CT parameters. TV and TA of extracranial FD lesions correlated strongly with skeletal outcomes including fractures and surgeries (p values ≤ 0.003). Subjects with impaired ambulation and scoliosis had significantly higher TV and TA values (P < 0.05), obtained from extracranial and spinal lesions, respectively. Craniofacial surgeries correlated with TV and TA of skull FD lesions (P < 0.001). Bone turnover markers, including alkaline phosphatase, N-telopeptides, and osteocalcin, were strongly correlated with TV and TA (P < 0.05) extracted from FD lesions in the entire skeleton. No associations were identified with SUV or SUV . Bone pain and age did not correlate with F-NaF PET/CT parameters. FD burden evaluated by F-NaF-PET/CT facilitates accurate assessment of FD activity, and correlates quantitatively with clinically-relevant skeletal outcomes. © 2019 American Society for Bone and Mineral Research.
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http://dx.doi.org/10.1002/jbmr.3738DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6744316PMC
September 2019

Deep learning opens new horizons in personalized medicine.

Biomed Rep 2019 Apr 13;10(4):215-217. Epub 2019 Mar 13.

Computational Biomedicine Laboratory (CBML), Institute of Computer Science (ICS), Foundation for Research and Technology Hellas (FORTH), 70013 Heraklion, Greece.

Although the idea of the personalization of patient care dates back to the time of Hippocrates, recent advances in diagnostic medical imaging and molecular medicine are gradually transforming healthcare services, by offering information and diagnostic tools enabling individualized patient management. Facilitating personalized / precision medicine requires taking into account multiple heterogenous parameters, such as sociodemographics, gene variability, environmental and lifestyle factors. Therefore, one of the most critical challenges in personalized medicine is the need to transform large, multi-modal data into decision support tools, capable of bridging the translational gap to the clinical setting. Towards these challenges, deep learning (DL) provides a novel approach, which enables obtaining or developing high-accuracy, multi-modal predictive models, that allow the implementation of the personalized medicine vision in the near future. DL is a highly effective strategy in addressing these challenges, with DL-based models leading to unprecedented results, matching or even improving state-of-the-art prediction/detection rates based on both intuitive and non-intuitive disease descriptors. These results hold promise for significant socio-economic benefits from the application of DL personalized medicine.
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http://dx.doi.org/10.3892/br.2019.1199DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6439426PMC
April 2019

Investigating the Role of Model-Based and Model-Free Imaging Biomarkers as Early Predictors of Neoadjuvant Breast Cancer Therapy Outcome.

IEEE J Biomed Health Inform 2019 09 31;23(5):1834-1843. Epub 2019 Jan 31.

Imaging biomarkers (IBs) play a critical role in the clinical management of breast cancer (BRCA) patients throughout the cancer continuum for screening, diagnosis, and therapy assessment, especially in the neoadjuvant setting. However, certain model-based IBs suffer from significant variability due to the complex workflows involved in their computation, whereas model-free IBs have not been properly studied regarding clinical outcome. In this study, IBs from 35 BRCA patients who received neoadjuvant chemotherapy (NAC) were extracted from dynamic contrast-enhanced MR imaging (DCE-MRI) data with two different approaches, a model-free approach based on pattern recognition (PR), and a model-based one using pharmacokinetic compartmental modeling. Our analysis found that both model-free and model-based biomarkers can predict pathological complete response (pCR) after the first cycle of NAC. Overall, eight biomarkers predicted the treatment response after the first cycle of NAC, with statistical significance (p-value < 0.05), and three at the baseline. The best pCR predictors at first follow-up, achieving high AUC and sensitivity and specificity more than 50%, were the hypoxic component with threshold 2 (AUC 90.4%) from the PR method, and the median value of k (AUC 73.4%) from the model-based approach. Moreover, the 80 percentile of v achieved the highest pCR prediction at baseline with AUC 78.5%. The results suggest that the model-free DCE-MRI IBs could be a more robust alternative to complex, model-based ones such as k and favor the hypothesis that the PR image-derived hypoxic image component captures actual tumor hypoxia information able to predict BRCA NAC outcome.
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http://dx.doi.org/10.1109/JBHI.2019.2895459DOI Listing
September 2019

CT analysis of anatomical distribution of melorheostosis challenges the sclerotome hypothesis.

Bone 2018 12 12;117:31-36. Epub 2018 Sep 12.

Clinical and Investigative Orthopedics Surgery Unit, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, United States of America.

Melorheostosis (MEL) is a rare disease of high bone mass with patchy skeletal distribution affecting the long bones. We recently reported somatic mosaic mutations in MAP2K1 in 8 of 15 patients with the disease. The unique anatomic distribution of melorheostosis is of great interest. The disease remains limited to medial or lateral side of the extremity with proximo-distal progression. This pattern of distribution has historically been attributed to sclerotomes (area of bone which is innervated by a single spinal nerve level). In a further analysis of our study on MEL, 30 recruited patients underwent whole body CT scans to characterize the anatomic distribution of the disease. Two radiologists independently reviewed these scans and compared it to the proposed map of sclerotomes. We found that the disease distribution conformed to the distribution of a single sclerotome in only 5 patients (17%). In another 12 patients, the lesions spanned parts of contiguous sclerotomes but did not involve the entire extent of the sclerotomes. Our findings raise concerns about the sclerotomal hypothesis being the definitive explanation for the pattern of anatomic distribution in MEL. We believe that the disease distribution can be explained by clonal proliferation of a mutated skeletal progenitor cell along the limb axis. Studies in mice models on clonal proliferation in limb buds mimic the patterns seen in melorheostosis. We also support this hypothesis by the dorso-ventral confinement of melorheostotic lesion in a patient with low allele frequency of MAP2K1-positive osteoblasts and low skeletal burden of the disease. This suggests that the mutation occurred after the formation of dorso-ventral plane. Further studies on limb development are needed to better understand the etiology, pathophysiology and pattern of disease distribution in all patients with MEL.
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http://dx.doi.org/10.1016/j.bone.2018.09.005DOI Listing
December 2018

Increased Metabolic Activity on 18F-Fluorodeoxyglucose Positron Emission Tomography-Computed Tomography in Human Immunodeficiency Virus-Associated Immune Reconstitution Inflammatory Syndrome.

Clin Infect Dis 2019 01;68(2):229-238

Division of Intramural Research, National Institute of Allergy and Infectious Diseases (NIAID), NIH, Bethesda.

Background: Immune reconstitution inflammatory syndrome (IRIS) represents an unexpected inflammatory response shortly after initiation of antiretroviral therapy (ART) in some human immunodeficiency virus (HIV)-infected patients with underlying neoplasia or opportunistic infections, including tuberculosis. We hypothesized that IRIS is associated with increased glycolysis and that 18F-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET/CT) could help identify high-risk subjects.

Methods: In this prospective cohort study, 30 HIV-infected patients (CD4+ count <100 cells/µL) underwent FDG-PET/CT scans at baseline and 4-8 weeks after ART initiation. Ten patients developed IRIS (6 mycobacterial).

Results: At baseline, total glycolytic activity, total lesion volume, and maximum standardized uptake values (SUVs) of pathologic FDG uptake (reflective of opportunistic disease burden) were significantly higher in IRIS vs non-IRIS (P = .010, .017, and .029, respectively) and significantly correlated with soluble inflammatory biomarkers (interferon-γ, myeloperoxidase, tumor necrosis factor, interleukin 6, soluble CD14). Baseline bone marrow (BM) and spleen FDG uptake was higher in mycobacterial IRIS specifically. After ART initiation, BM and spleen mean SUV decreased in non-IRIS (P = .004, .013) but not IRIS subjects. Our results were supported by significantly higher glucose transporter 1 (Glut-1) expression of CD4+ cells and monocytes after ART initiation in IRIS/mycobacterial IRIS compared with non-IRIS patients.

Conclusions: We conclude that increased pathologic metabolic activity on FDG-PET/CT prior to ART initiation is associated with IRIS development and correlates with inflammatory biomarkers. Abnormally elevated BM and spleen metabolism is associated with mycobacterial IRIS, HIV viremia, and Glut-1 expression on CD4+ cells and monocytes.

Clinical Trials Registration: NCT02147405.
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http://dx.doi.org/10.1093/cid/ciy454DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6321853PMC
January 2019

Distinct Clinical and Pathological Features of Melorheostosis Associated With Somatic MAP2K1 Mutations.

J Bone Miner Res 2019 01 14;34(1):145-156. Epub 2018 Sep 14.

Clinical and Investigative Orthopedics Surgery Unit, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), National Institutes of Health (NIH), Bethesda, MD, USA.

Melorheostosis is a rare hyperostotic disease of the long bones classically characterized by a "dripping candle-wax" radiographic appearance. We recently described somatic activating mutations in MAP2K1 as a cause of melorheostosis. Here, we report distinguishing characteristics of patients with MAP2K1-positive melorheostosis. Fifteen unrelated patients with radiographic appearance of melorheostosis underwent paired biopsies of affected and unaffected bone for whole-exome sequencing, histology, and cell culture. Eight patients with mutations in MAP2K1 in affected bone were compared to the seven MAP2K1-negative patients to identify distinguishing characteristics. Patients with MAP2K1-positive melorheostosis had a distinct phenotype with classic "dripping candle-wax" appearance on radiographs (p = 0.01), characteristic vascular lesions on skin overlying affected bone (p = 0.01), and higher prevalence of extraosseous mineralization and joint involvement (p = 0.04 for both). Melorheostotic bone from both MAP2K1-positive and MAP2K1-negative patients showed two zones of distinct morphology-an outer segment of parallel layers of primary lamellar bone and a deeper zone of intensely remodeled highly porous osteonal-like bone. Affected bone from MAP2K1-positive patients showed excessive osteoid (p = 0.0012), increased number of osteoblasts (p = 0.012) and osteoclasts (p = 0.04), and increased vascularity on histology in comparison to paired unaffected bone which was not seen in affected bone in most MAP2K1-negative patients. The identification of a distinct phenotype of patients with MAP2K1-positive melorheostosis demonstrates clinical and genetic heterogeneity among patients with the disease. Further studies are needed to better understand the underlying pathophysiology and associated skin findings. © 2018 American Society for Bone and Mineral Research.
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http://dx.doi.org/10.1002/jbmr.3577DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7577747PMC
January 2019

Joint solution for PET image segmentation, denoising, and partial volume correction.

Med Image Anal 2018 05 28;46:229-243. Epub 2018 Mar 28.

University of Central Florida, Orlando, FL, USA. Electronic address:

Segmentation, denoising, and partial volume correction (PVC) are three major processes in the quantification of uptake regions in post-reconstruction PET images. These problems are conventionally addressed by independent steps. In this study, we hypothesize that these three processes are dependent; therefore, jointly solving them can provide optimal support for quantification of the PET images. To achieve this, we utilize interactions among these processes when designing solutions for each challenge. We also demonstrate that segmentation can help in denoising and PVC by locally constraining the smoothness and correction criteria. For denoising, we adapt generalized Anscombe transformation to Gaussianize the multiplicative noise followed by a new adaptive smoothing algorithm called regional mean denoising. For PVC, we propose a volume consistency-based iterative voxel-based correction algorithm in which denoised and delineated PET images guide the correction process during each iteration precisely. For PET image segmentation, we use affinity propagation (AP)-based iterative clustering method that helps the integration of PVC and denoising algorithms into the delineation process. Qualitative and quantitative results, obtained from phantoms, clinical, and pre-clinical data, show that the proposed framework provides an improved and joint solution for segmentation, denoising, and partial volume correction.
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http://dx.doi.org/10.1016/j.media.2018.03.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6080255PMC
May 2018

Holistic classification of CT attenuation patterns for interstitial lung diseases via deep convolutional neural networks.

Comput Methods Biomech Biomed Eng Imaging Vis 2018 6;6(1):1-6. Epub 2016 Jun 6.

Radiology and Imaging Sciences, Clinical Center, National Institutes of Health (NIH), Bethesda, MD, USA.

Interstitial lung diseases (ILD) involve several abnormal imaging patterns observed in computed tomography (CT) images. Accurate classification of these patterns plays a significant role in precise clinical decision making of the extent and nature of the diseases. Therefore, it is important for developing automated pulmonary computer-aided detection systems. Conventionally, this task relies on experts' manual identification of regions of interest (ROIs) as a prerequisite to diagnose potential diseases. This protocol is time consuming and inhibits fully automatic assessment. In this paper, we present a new method to classify ILD imaging patterns on CT images. The main difference is that the proposed algorithm uses the entire image as a holistic input. By circumventing the prerequisite of manual input ROIs, our problem set-up is significantly more difficult than previous work but can better address the clinical workflow. Qualitative and quantitative results using a publicly available ILD database demonstrate state-of-the-art classification accuracy under the patch-based classification and shows the potential of predicting the ILD type using holistic image.
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http://dx.doi.org/10.1080/21681163.2015.1124249DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5881940PMC
June 2016

Improving diagnosis, prognosis and prediction by using biomarkers in CRC patients (Review).

Oncol Rep 2018 Jun 21;39(6):2455-2472. Epub 2018 Mar 21.

Laboratory of Anatomy‑Histology‑Embryology, Medical School, University of Crete, 71110 Heraklion, Greece.

Colorectal cancer (CRC) is among the most common cancers. In fact, it is placed in the third place among the most diagnosed cancer in men, after lung and prostate cancer, and in the second one for the most diagnosed cancer in women, following breast cancer. Moreover, its high mortality rates classifies it among the leading causes of cancer‑related death worldwide. Thus, in order to help clinicians to optimize their practice, it is crucial to introduce more effective tools that will improve not only early diagnosis, but also prediction of the most likely progression of the disease and response to chemotherapy. In that way, they will be able to decrease both morbidity and mortality of their patients. In accordance with that, colon cancer research has described numerous biomarkers for diagnostic, prognostic and predictive purposes that either alone or as part of a panel would help improve patient's clinical management. This review aims to describe the most accepted biomarkers among those proposed for use in CRC divided based on the clinical specimen that is examined (tissue, faeces or blood) along with their restrictions. Lastly, new insight in CRC monitoring will be discussed presenting promising emerging biomarkers (telomerase activity, telomere length and micronuclei frequency).
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http://dx.doi.org/10.3892/or.2018.6330DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5983921PMC
June 2018

Update on radionuclide therapy in oncology.

Oncol Lett 2017 Dec 5;14(6):7011-7015. Epub 2017 Oct 5.

Departament of Toxicology, Faculty of Pharmacy, 'Carol Davila' University of Medicine and Pharmacy, 020956 Bucharest, Romania.

Unstable isotopes and their capacity to emit ionizing radiation have been employed in clinical practice not only for diagnostic, but also for therapeutic purposes, with significant contribution in several fields of medicine and primarily in the management of oncologic patients. Their efficacy is associated with their ability to provide the targeted delivery of ionizing radiation for a determined duration. These compounds can be used for curative or palliative treatment, as well as for a diagnostic-therapeutic (theranostic) approach. This review summarises the most recent trends in radionuclide treatment for several malignancies, including prostate cancer, neuroendocrine tumours, and hematological and thyroid malignancies, in which radionuclide-based therapies have been employed with high effectiveness.
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http://dx.doi.org/10.3892/ol.2017.7141DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5754838PMC
December 2017