Clinical value of whole-body PET/CT in patients with active rheumatic diseases

Advanced imaging techniques may enable early diagnosis and monitoring of therapy in various rheumatic diseases. To prevent irreversible tissue damage, inflammatory rheumatic disease must be diagnosed and treated in pre-clinical stages, requiring highly sensitive detection techniques. Positron emission tomography (PET) provides highly sensitive, quantitative imaging at a molecular level, revealing the important pathophysiological processes underlying inflammation. This review provides an overview of the current utility of ¹⁸?F-fluorodeoxyglucose (FDG)-PET/computed tomography (CT) in patients with active rheumatic diseases such as rheumatoid arthritis, spondyloarthritis, polymyalgia rheumatica, adult-onset Still’s disease, relapsing polychondritis, immunoglobulin G4-related disease, large-vessel vasculitis, Wegener’s granulomatosis, polymyositis, and dermatomyositis. We also discuss the role of FDG-PET/CT in the diagnosis and monitoring of these diseases.     

Enriched Au nanoclusters with mesoporous silica nanoparticles for improved fluorescence/computed tomography dual‐modal imaging

ObjectivesAu nanoclusters (AuNCs) have been used widely in fluorescence bio‐imaging because of their good fluorescence, small particle size and non‐cytotoxicity. AuNCs are also efficient in computed tomography (CT) imaging. Hence, a dual‐modal imaging probe can be constructed without any complicated modification processes by exploiting the excellent performance of AuNCs. In the present study, AuNCs were enriched with mesoporous silica nanoparticles (MSNs) to obtain enhanced fluorescence/CT dual‐modal imaging, which was capable of acquiring more imaging information for diseases compared with single‐mode imaging.Materials and methodsBiocompatible bovine serum albumin (BSA)‐capped AuNCs were prepared and loaded into amine‐functionalized MSNs to form MSN@AuNCs. BSA‐AuNCs, MSNs, and MSN@AuNCs were characterized by ultraviolet‐visible (UV‐vis) spectra, transmission electron microscopy (TEM), fluorescence spectra, and zeta potential. CT imaging was recorded using micro‐CT scanning. Fluorescence imaging was measured using confocal laser scanning microscopy and flow cytometry.ResultsThe prepared AuNCs and MSNs possessed good properties as previously reported. The fluorescence intensity and CT value of the AuNCs were enhanced after being enriched with MSNs. The nanoparticles were both non‐cytotoxic. Confocal laser scanning microscopy and flow cytometry indicated that MSN@AuNCs in CAL‐27 cells showed improved fluorescence imaging compared with simple AuNCs at the same concentration.ConclusionsThe results revealed that the strategy of enriching AuNCs with MSNs can obtain highly sensitive fluorescence/CT dual‐modal imaging, which indicated the potential of this nanoparticle in the diagnosis and treatment of disease.     

Capacities of computed tomographic angiography in the diagnosis and estimation of the site, pattern, and degree of vascular bed lesion in nonspecific aortoarteritis

Nonspecific aortoarteritis (NAA) is a chronic inflammatory disease that affects the aorta and its branches. The clinical manifestations of this disease are of a great variety and depend on the site of a lesion and the stage of the disease. A wide range of highly informative noninvasive imaging techniques, such as duplex scanning (DS), magnetic resonance imaging (MRI), and computed tomography (CT) of the aorta and its branches, are used to make a more accurate diagnosis and to determine the site and extent of a vascular bed lesion. The given clinical example suggests that CT angiography of the aorta and its branches is a high-precision technique in determining the site of vascular bed lesion in patients with NAA and the pattern and extent of arterial involvement and that it may be used for both the diagnosis of the disease at its developmental stages and the monitoring of the vessels during pathogenetic therapy.     

Inguinal lymphadenopathy of cat-scratch disease mimicking malignant hemopathy on 18FDG-PET/CT

18-Fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸FDG-PET/CT) is a valuable imaging technique for the diagnosis and staging of malignant pathologies. Nevertheless, false positive exams exist, especially in the case of infectious or inflammatory diseases. We report a case of a 39-year-old man who presented a cat-scratch disease (CSD), which was revealed through hypermetabolic inguinal lymphadenopathy on ¹⁸FDG-PET/CT mimicking malignant hemopathy. Finally, biopsy and PCR analysis revealed Bartonella henselae infection.     

On the Utility of MIBG SPECT/CT in Evaluating Cardiac Sympathetic Dysfunction in Lewy Body Diseases

BackgroundAbnormal cardiac uptake of ¹²³I-metaiodobenzylguanidine (¹²³I-MIBG) is a diagnostic marker of Lewy body diseases (LBDs), e.g., Parkinson’s disease (PD) and dementia with Lewy bodies (DLB). Planar imaging is generally used to assess cardiac sympathetic dysfunction in ¹²³I-MIBG scintigraphy; however, its clinical utility requires further improvement. We hypothesized that the co-registration of single-photon emission tomography (SPECT) and computed tomography (CT) images would improve the diagnostic accuracy of ¹²³I-MIBG cardiac scintigraphy for LBDs. This study sought to evaluate the effects of SPECT/CT imaging on ¹²³I-MIBG cardiac scintigraphy for diagnosing LBDs.MethodsWe retrospectively investigated data of 54 patients (consecutive 18 patients in each PD, DLB, and idiopathic normal pressure hydrocephalus [iNPH] groups) who underwent ¹²³I-MIBG cardiac scintigraphy (planar and SPECT/CT) because of suspected LBDs at the Tohoku University hospital from June 2012 to June 2015. We compared the diagnostic accuracies of the conventional planar ¹²³I-MIBG method and SPECT/CT methods (manual and semi-automatic).ResultsIn the conventional planar analysis, ¹²³I-MIBG uptake decreased only in the DLB group compared with the iNPH group. In contrast, the SPECT/CT analysis revealed significantly lower ¹²³I-MIBG uptake in both the PD and DLB groups compared with the iNPH group. Furthermore, a receiver operating characteristic analysis revealed that both the manual and semi-automatic SPECT/CT methods were superior to the conventional planar method in differentiating the 3 disorders.ConclusionsSPECT/CT ¹²³I-MIBG cardiac scintigraphy can detect mild cardiac sympathetic dysfunction in LDBs. Our results suggest that the SPECT/CT technique improves diagnostic accuracy for LBDs.     

Acoustic Property Reconstruction of a Neonate Yangtze Finless Porpoise's (Neophocaena asiaeorientalis) Head Based on CT Imaging

The reconstruction of the acoustic properties of a neonate finless porpoise’s head was performed using X-ray computed tomography (CT). The head of the deceased neonate porpoise was also segmented across the body axis and cut into slices. The averaged sound velocity and density were measured, and the Hounsfield units (HU) of the corresponding slices were obtained from computed tomography scanning. A regression analysis was employed to show the linear relationships between the Hounsfield unit and both sound velocity and density of samples. Furthermore, the CT imaging data were used to compare the HU value, sound velocity, density and acoustic characteristic impedance of the main tissues in the porpoise’s head. The results showed that the linear relationships between HU and both sound velocity and density were qualitatively consistent with previous studies on Indo-pacific humpback dolphins and Cuvier’s beaked whales. However, there was no significant increase of the sound velocity and acoustic impedance from the inner core to the outer layer in this neonate finless porpoise’s melon.     

Detection of Pancreatic Carcinomas by Imaging Lactose-Binding Protein Expression in Peritumoral Pancreas Using [18F]Fluoroethyl-Deoxylactose PET/CT

Background

Early diagnosis of pancreatic carcinoma with highly sensitive diagnostic imaging methods could save lives of many thousands of patients, because early detection increases resectability and survival rates. Current non-invasive diagnostic imaging techniques have inadequate resolution and sensitivity for detection of small size (∼2–3 mm) early pancreatic carcinoma lesions. Therefore, we have assessed the efficacy of positron emission tomography and computer tomography (PET/CT) imaging with β-O-D-galactopyranosyl-(1,4′)-2′-deoxy-2′-[¹⁸F]fluoroethyl-D-glucopyranose ([¹⁸F]FEDL) for detection of less than 3 mm orthotopic xenografts of L3.6pl pancreatic carcinomas in mice. [¹⁸F]FEDL is a novel radioligand of hepatocarcinoma-intestine-pancreas/pancreatitis-associated protein (HIP/PAP), which is overexpressed in peritumoral pancreatic acinar cells.

Methodology/Principal Findings

Dynamic PET/CT imaging demonstrated rapid accumulation of [¹⁸F]FEDL in peritumoral pancreatic tissue (4.04±2.06%ID/g), bi-exponential blood clearance with half-lives of 1.65±0.50 min and 14.14±3.60 min, and rapid elimination from other organs and tissues, predominantly by renal clearance. Using model-independent graphical analysis of dynamic PET data, the average distribution volume ratio (DVR) for [¹⁸F]FEDL in peritumoral pancreatic tissue was estimated as 3.57±0.60 and 0.94±0.72 in sham-operated control pancreas. Comparative analysis of quantitative autoradiographic images and densitometry of immunohistochemically stained and co-registered adjacent tissue sections demonstrated a strong linear correlation between the magnitude of [¹⁸F]FEDL binding and HIP/PAP expression in corresponding regions (r = 0.88). The in situ analysis demonstrated that at least a 2–4 fold apparent lesion size amplification was achieved for submillimeter tumors and to nearly half a murine pancreas for tumors larger than 3 mm.

Conclusion/Significance

We have demonstrated the feasibility of detection of early pancreatic tumors by non-invasive imaging with [¹⁸F]FEDL PET/CT of tumor biomarker HIP/PAP over-expressed in peritumoral pancreatic tissue. Non-invasive non-invasive detection of early pancreatic carcinomas with [¹⁸F]FEDL PET/CT imaging should aid the guidance of biopsies and additional imaging procedures, facilitate the resectability and improve the overall prognosis.     

Is 3-Tesla Gd-EOB-DTPA-Enhanced MRI with Diffusion-Weighted Imaging Superior to 64-Slice Contrast-Enhanced CT for the Diagnosis of Hepatocellular Carcinoma?

Objectives

To compare 64-slice contrast-enhanced computed tomography (CT) with 3-Tesla magnetic resonance imaging (MRI) using Gd-EOB-DTPA for the diagnosis of hepatocellular carcinoma (HCC) and evaluate the utility of diffusion-weighted imaging (DWI) in this setting.

Methods

3-phase-liver-CT was performed in fifty patients (42 male, 8 female) with suspected or proven HCC. The patients were subjected to a 3-Tesla-MRI-examination with Gd-EOB-DTPA and diffusion weighted imaging (DWI) at b-values of 0, 50 and 400 s/mm². The apparent diffusion coefficient (ADC)-value was determined for each lesion detected in DWI. The histopathological report after resection or biopsy of a lesion served as the gold standard, and a surrogate of follow-up or complementary imaging techniques in combination with clinical and paraclinical parameters was used in unresected lesions. Diagnostic accuracy, sensitivity, specificity, and positive and negative predictive values were evaluated for each technique.

Results

MRI detected slightly more lesions that were considered suspicious for HCC per patient compared to CT (2.7 versus 2.3, respectively). ADC-measurements in HCC showed notably heterogeneous values with a median of 1.2±0.5×10⁻³ mm²/s (range from 0.07±0.1 to 3.0±0.1×10⁻³ mm²/s). MRI showed similar diagnostic accuracy, sensitivity, and positive and negative predictive values compared to CT (AUC 0.837, sensitivity 92%, PPV 80% and NPV 90% for MRI vs. AUC 0.798, sensitivity 85%, PPV 79% and NPV 82% for CT; not significant). Specificity was 75% for both techniques.

Conclusions

Our study did not show a statistically significant difference in detection in detection of HCC between MRI and CT. Gd-EOB-DTPA-enhanced MRI tended to detect more lesions per patient compared to contrast-enhanced CT; therefore, we would recommend this modality as the first-choice imaging method for the detection of HCC and therapeutic decisions. However, contrast-enhanced CT was not inferior in our study, so that it can be a useful image modality for follow-up examinations.     

PET/CT影像技术在神经退行性疾病动物模型研究中的应用

PET和CT影像技术是肿瘤、痴呆症、心脑血管病等的重要临床诊断技术,近年发展的小动物PET/CT成为对人类疾病动物模型,尤其是小动物模型进行比较医学研究的最新工具,能够活体无创的、动态的、定量的从分子水平观察动物的生理生化变化,进行代谢显像、受体显像、基因表达显像等。已经广泛应用于对神经退行性疾病的研究中.本文介绍了近年来一些小动物PET/CT在退行性疾病的研究中的最新应用。     

Effectiveness of imaging modalities for screening IgG4-related dacryoadenitis and sialadenitis (Mikulicz’s disease) and for differentiating it from Sj?gren’s syndrome (SS), with an emphasis on sonography

IntroductionThe aim of this study was to clarify the effectiveness of various imaging modalities and characteristic imaging features in the screening of IgG4-related dacryoadenitis and sialadenitis (IgG4-DS), and to show the differences in the imaging features between IgG4-DS and Sjögren’s syndrome (SS).MethodsThirty-nine patients with IgG4-DS, 51 with SS and 36 with normal salivary glands were enrolled. Images of the parotid and submandibular glands obtained using sonography, 2-[¹⁸F]-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (FDG-PET/CT), computed tomography (CT) and magnetic resonance imaging (MRI) were retrospectively analyzed. Six oral and maxillofacial radiologists randomly reviewed the arranged image sets under blinded conditions. Each observer scored the confidence rating regarding the presence of the characteristic imaging findings using a 5-grade rating system. After scoring various findings, diagnosis was made as normal, IgG4-DS or SS, considering all findings for each case.ResultsOn sonography, multiple hypoechoic areas and hyperechoic lines and/or spots in the parotid glands and obscuration of submandibular gland configuration were detected mainly in patients with SS (median scores 4, 4 and 3, respectively). Reticular and nodal patterns were observed primarily in patients with IgG4-DS (median score 5). FDG-PET/CT revealed a tendency for abnormal ¹⁸F-FDG accumulation and swelling of both the parotid and submandibular glands in patients with IgG4-DS, particularly in the submandibular glands. On MRI, SS had a high score regarding the findings of a salt-and-pepper appearance and/or multiple cystic areas in the parotid glands (median score 4.5). Sonography showed the highest values among the four imaging modalities for sensitivity, specificity and accuracy. There were significant differences between sonography and CT (p = 0.0001) and between sonography and FDG-PET/CT (p = 0.0058) concerning accuracy.ConclusionsChanges in the submandibular glands affected by IgG4-DS could be easily detected using sonography (characteristic bilateral nodal/reticular change) and FDG-PET/CT (abnormal ¹⁸F-FDG accumulation). Even inexperienced observers could detect these findings. In addition, sonography could also differentiate SS. Consequently, we recommend sonography as a modality for the screening of IgG4-DS, because it is easy to use, involves no radiation exposure and is an effective imaging modality.     

Three-dimensional segmentation and depth-encoded visualization of choroidal vasculature using swept-source optical coherence tomography

The choroid provides nutritional support for the retinal pigment epithelium and photoreceptors. Choroidal dysfunction plays a major role in several of the most important causes of vision loss including age-related macular degeneration, myopic degeneration, and pachychoroid diseases such as central serous chorioretinopathy and polypoidal choroidal vasculopathy. We describe an imaging technique using depth-resolved swept-source optical coherence tomography (SS-OCT) that provides full-thickness three-dimensional (3D) visualization of choroidal anatomy including topographical features of individual vessels. Enrolled subjects with different clinical manifestations within the pachychoroid disease spectrum underwent 15 mm × 9 mm volume scans centered on the fovea. A fully automated method segmented the choroidal vessels using their hyporeflective lumens. Binarized choroidal vessels were rendered in a 3D viewer as a vascular network within a choroidal slab. The network of choroidal vessels was color depth-encoded with a reference to the Bruch’s membrane segmentation. Topographical features of the choroidal vasculature were characterized and compared with choroidal imaging obtained with indocyanine green angiography (ICGA) from the same subject. The en face SS-OCT projections of the larger choroid vessels closely resembled to that obtained with ICGA, with the automated SS-OCT approach proving additional depth-encoded 3D information. In 16 eyes with pachychoroid disease, the SS-OCT approach added clinically relevant structural details, including choroidal thickness and vessel depth, which the ICGA studies could not provide. Our technique appears to advance the in vivo visualization of the full-thickness choroid, successfully reveals the topographical features of choroidal vasculature, and shows potential for further quantitative analysis when compared with other choroidal imaging techniques. This improved visualization of choroidal vasculature and its 3D structure should provide an insight into choroid-related disease mechanisms as well as their responses to treatment.     

Mouse models in neurological disorders: Applications of non-invasive imaging

Neuroimaging techniques represent powerful tools to assess disease-specific cellular, biochemical and molecular processes non-invasively in vivo. Besides providing precise anatomical localisation and quantification, the most exciting advantage of non-invasive imaging techniques is the opportunity to investigate the spatial and temporal dynamics of disease-specific functional and molecular events longitudinally in intact living organisms, so called molecular imaging (MI). Combining neuroimaging technologies with in vivo models of neurological disorders provides unique opportunities to understand the aetiology and pathophysiology of human neurological disorders. In this way, neuroimaging in mouse models of neurological disorders not only can be used for phenotyping specific diseases and monitoring disease progression but also plays an essential role in the development and evaluation of disease-specific treatment approaches. In this way MI is a key technology in translational research, helping to design improved disease models as well as experimental treatment protocols that may afterwards be implemented into clinical routine. The most widely used imaging modalities in animal models to assess in vivo anatomical, functional and molecular events are positron emission tomography (PET), magnetic resonance imaging (MRI) and optical imaging (OI). Here, we review the application of neuroimaging in mouse models of neurodegeneration (Parkinson's disease, PD, and Alzheimer's disease, AD) and brain cancer (glioma).     

An Experimental Study on 131I-CHIBA-1001: A Radioligand for α7 Nicotinic Acetylcholine Receptors

Objective

The α7 nicotinic acetylcholine receptors (nAChRs) play a vital role in the pathophysiology of neuropsychiatric diseases such as Alzheimer’s disease and depression. However, there is currently no suitable positron emission tomography (PET) or Single-Photon Emission Computed Tomography (SPECT) radioligands for imaging α7 nAChRs in brain. Here our aim is to radiosynthesize a novel SPECT radioligand ¹³¹I-CHIBA-1001 for whole body biodistribution study and in vivo imaging of α7 nAChRs in brain.

Method

¹³¹I-CHIBA-1001 was radiosynthesized by chloramine-T method. Different conditions of reaction time and temperature were tested to get a better radiolabeling yield. Radiolabeling yield and radiochemical purities of ¹³¹I-CHIBA-1001 were analyzed by thin layer chromatography (TLC) and high-performance liquid chromatography (HPLC) system. Whole body biodistribution study was performed at different time points post injection of ¹³¹I-CHIBA-1001 in KM mice. Monkey subject was used for in vivo SPECT imaging in brain.

Result

The radiolabeling yield of ¹³¹I-CHIBA-1001 reached 96% within 1.5∼2.0 h at 90∼95°C. The radiochemical purity reached more than 99% after HPLC purification. ¹³¹I-CHIBA-1001 was highly stable in saline and fresh human serum in room temperature and 37°C separately. The biodistribution data of brain at 15, 30, and 60 min were 11.05±1.04%ID/g, 8.8±0.04%ID/g and 6.28±1.13%ID/g, respectively. In experimental SPECT imaging, the distribution of radioactivity in the brain regions was paralleled with the distribution of α7 nAChRs in the monkey brain. Moreover, in the blocking SPECT imaging study, the selective α7 nAChR agonist SSR180711 blocked the radioactive uptake in the brain successfully.

Conclusion

The CHIBA-1001 can be successfully radiolabeled with ¹³¹I using the chloramine-T method. ¹³¹I-CHIBA-1001 can successfully accumulate in the monkey brain and image the α7 acetylcholine receptors. ¹³¹I-CHIBA-1001 can be a candidate for imagingα7 acetylcholine receptors, which will be of great value for the diagnosis and treatment of mental diseases.     

Changes in Retinal Function and Morphology Are Early Clinical Signs of Disease in Cattle with Bovine Spongiform Encephalopathy

Bovine spongiform encephalopathy (BSE) belongs to a group of fatal, transmissible protein misfolding diseases known as transmissible spongiform encephalopathies (TSEs). All TSEs are caused by accumulation of misfolded prion protein (PrP^Sc) throughout the central nervous system (CNS), which results in neuronal loss and ultimately death. Like other protein misfolding diseases including Parkinson’s disease and Alzheimer’s disease, TSEs are generally not diagnosed until the onset of disease after the appearance of unequivocal clinical signs. As such, identification of the earliest clinical signs of disease may facilitate diagnosis. The retina is the most accessible part of the central nervous system, and retinal pathology in TSE affected animals has been previously reported. Here we describe antemortem changes in retinal function and morphology that are detectable in BSE inoculated animals several months (up to 11 months) prior to the appearance of any other signs of clinical disease. We also demonstrate that differences in the severity of these clinical signs reflect the amount of PrP^Sc accumulation in the retina and the resulting inflammatory response of the tissue. These results are the earliest reported clinical signs associated with TSE infection and provide a basis for understanding the pathology and evaluating therapeutic interventions.     

多功能磁共振造影剂研究进展

磁共振成像技术因对人体无创、任意方向断层扫描三维图像且分辨率较高、提供形态与功能两方面诊断评价等突出优点,成为了临床上用于疾病诊断的重要手段之一。临床上使用磁共振造影剂可以提高成像的分辨率和灵敏度,提高图像质量,增强对比度和可读性。但是,各种成像技术由于实现原理不同,具有各自的优势和缺陷,靠传统单一的诊断模式无法提供疾病的全面信息,因而在对各种复杂疾病进行诊断时会受到一定的限制。因此,将磁共振成像与其他成像技术如CT成像、超声成像等联合起来使用,则可以达到优势互补的效果,能为疾病的临床诊断提供更快捷精确的信息,同时可将磁共振成像与各种治疗方式结合在一起,即开发基于磁共振成像的诊断治疗一体化试剂,以实现对疾病的即时治疗和实时监控。本文主要介绍了磁共振成像造影剂的原理和种类,并且综述了目前国内外在基于磁共振成像的多功能造影剂/诊疗制剂这一领域的研究进展,最后就未来可能的研究方向进行了展望。     

Brown Adipose Tissue Response Dynamics: In Vivo Insights with the Voltage Sensor 18F-Fluorobenzyl Triphenyl Phosphonium

Brown adipose tissue (BAT) thermogenesis is an emerging target for prevention and treatment of obesity. Mitochondria are the heat generators of BAT. Yet, there is no noninvasive means to image the temporal dynamics of the mitochondrial activity in BAT in vivo. Here, we report a technology for quantitative monitoring of principal kinetic components of BAT adaptive thermogenesis in the living animal, using the PET imaging voltage sensor ¹⁸F-fluorobenzyltriphenylphosphonium (¹⁸F-FBnTP). ¹⁸F-FBnTP targets the mitochondrial membrane potential (ΔΨm)—the voltage analog of heat produced by mitochondria. Dynamic ¹⁸F-FBnTP PET imaging of rat’s BAT was acquired just before and during localized skin cooling or systemic pharmacologic stimulation, with and without administration of propranolol. At ambient temperature, ¹⁸F-FBnTP demonstrated rapid uptake and prolonged steady-state retention in BAT. Conversely, cold-induced mitochondrial uncoupling resulted in an immediate washout of ¹⁸F-FBnTP from BAT, which was blocked by propranolol. Specific variables of BAT evoked activity were identified and quantified, including response latency, magnitude and kinetics. Cold stimulation resulted in partial washout of ¹⁸F-FBnTP (39.1%±14.4% of basal activity). The bulk of ¹⁸F-FBnTP washout response occurred within the first minutes of the cold stimulation, while colonic temperature remained nearly intact. Drop of colonic temperature to shivering zone did not have an additive effect. The ß3-adrenergic agonist CL-316,243 elicited ¹⁸F-FBnTP washout from BAT of kinetics similar to those caused by cold stimulation. Thus, monitoring ΔΨm in vivo using ¹⁸F-FBnTP PET provides insights into the kinetic physiology of BAT. ¹⁸F-FBnTP PET depicts BAT as a highly sensitive and rapidly responsive organ, emitting heat in short burst during the first minutes of stimulation, and preceding change in core temperature. ¹⁸F-FBnTP PET provides a novel set of quantitative metrics highly important for identifying novel therapeutic targets at the mitochondrial level, for developing means to maximize BAT mass and activity, and assessing intervention efficacy.     

A Novel Detection Platform for Shrimp White Spot Syndrome Virus Using an ICP11-Dependent Immunomagnetic Reduction (IMR) Assay

Shrimp white spot disease (WSD), which is caused by white spot syndrome virus (WSSV), is one of the world’s most serious shrimp diseases. Our objective in this study was to use an immunomagnetic reduction (IMR) assay to develop a highly sensitive, automatic WSSV detection platform targeted against ICP11 (the most highly expressed WSSV protein). After characterizing the magnetic reagents (Fe₃O₄ magnetic nanoparticles coated with anti ICP11), the detection limit for ICP11 protein using IMR was approximately 2 x 10⁻³ ng/ml, and the linear dynamic range of the assay was 0.1~1 x 10⁶ ng/ml. In assays of ICP11 protein in pleopod protein lysates from healthy and WSSV-infected shrimp, IMR signals were successfully detected from shrimp with low WSSV genome copy numbers. We concluded that this IMR assay targeting ICP11 has potential for detecting the WSSV.     

18?F-Fluoride positron emission tomography/computed tomography for noninvasive in vivo quantification of pathophysiological bone metabolism in experimental murine arthritis

Introduction

Evaluation of disease severity in experimental models of rheumatoid arthritis is inevitably associated with assessment of structural bone damage. A noninvasive imaging technology allowing objective quantification of pathophysiological alterations of bone structure in rodents could substantially extend the methods used to date in preclinical arthritis research for staging of autoimmune disease severity or efficacy of therapeutical intervention. Sodium ¹⁸ F-fluoride (¹⁸ F-NaF) is a bone-seeking tracer well-suited for molecular imaging. Therefore, we systematically examined the use of ¹⁸ F-NaF positron emission tomography/computed tomography (PET/CT) in mice with glucose-6-phosphate isomerase (G6PI)–induced arthritis for quantification of pathological bone metabolism.

Methods

F-fluoride was injected into mice before disease onset and at various time points of progressing experimental arthritis. Radioisotope accumulation in joints in the fore- and hindpaws was analyzed by PET measurements. For validation of bone metabolism quantified by ¹⁸ F-fluoride PET, bone surface parameters of high-resolution μCT measurements were used.

Results

Before clinical arthritis onset, no distinct accumulation of ¹⁸ F-fluoride was detectable in the fore- and hindlimbs of mice immunized with G6PI. In the course of experimental autoimmune disease, ¹⁸ F-fluoride bone uptake was increased at sites of enhanced bone metabolism caused by pathophysiological processes of autoimmune disease. Moreover, ¹⁸ F-fluoride signaling at different stages of G6PI-induced arthritis was significantly correlated with the degree of bone destruction. CT enabled identification of exact localization of ¹⁸ F-fluoride signaling in bone and soft tissue.

Conclusions

The results of this study suggest that small-animal PET/CT using ¹⁸ F-fluoride as a tracer is a feasible method for quantitative assessment of pathophysiological bone metabolism in experimental arthritis. Furthermore, the possibility to perform repeated noninvasive measurements in vivo allows longitudinal study of therapeutical intervention monitoring.     

Elevated Muscle-Specific miRNAs in Serum of Myotonic Dystrophy Patients Relate to Muscle Disease Progress

The discovery of reliable and sensitive blood biomarkers is useful for the diagnosis, monitoring and potential future therapy of diseases. Recently, microRNAs (miRNAs) have been identified in blood circulation and might have the potential to be used as biomarkers for several diseases and clinical conditions. Myotonic Dystrophy type 1 (DM1) is the most common form of adult-onset muscular dystrophy primarily characterized by muscle myotonia, weakness and atrophy. Previous studies have shown an association between miRNAs and DM1 in muscle tissue and, recently, in plasma. The aim of this study was to detect and assess muscle-specific miRNAs as potential biomarkers of DM1 muscle wasting, an important parameter in the disease’s natural history. Disease stable or progressive DM1 patients with muscle weakness and wasting were recruited and enrolled in the study. RNA isolated from participants’ serum was used to assess miRNA levels. Results suggest that the levels of muscle-specific miRNAs are correlated with the progression of muscle wasting and weakness observed in the DM1 patients. Specifically, miR-1, miR-133a, miR133b and miR-206 serum levels were found elevated in DM1 patients with progressive muscle wasting compared to disease stable DM1 patients. Based on these results, we propose that muscle-specific miRNAs might be useful molecular biomarkers for monitoring the progress of muscle atrophy in DM1 patients.