Optical molecular imaging is a powerful imaging method, which can in vivo monitor physiological and pathobiological processes at the cellular and molecular levels, as opposed to the anatomical level, bridging the gap between imaging and biological processes. Because of its relevance in cardiovascular diseases research, the use of this technology for imaging of cardiovascular diseases advances at a rapid pace in the past decade. This review summarizes the optical molecular imaging methods for imaging the specific targets in cardiovascular diseases, which hold promise for in vivo applications in cardiovascular diseases research. Collectively, in vivo optical molecular imaging may be highly suitable for discriminating targets that play key roles in the occurrence and development of the instable atherosclerosis, thrombogenesis, myocardial infarction, myocardial apoptosis, angiogenesis, as well as in cardiac cell transplantation. Keywords: Bioluminescent imaging, cardiovascular diseases, fluorescence molecular tomography, near-infrared fluorescence imaging, optical imaging.
Cardiovascular diseases are generally synonymous with atherosclerosis and cardiac events from occluded vessels, although a multitude of other clinically significant diseases with occluded arteries exist. They often revolve around inflammatory processes, locally within or around the vessels as well as systemic, and they may result in significant morbidity and mortality. The systemic inflammatory component may manifest itself throughout the vasculature, but structural changes are often limited, which hamper the use of conventional and localized structural imaging. On the other hand, sensitive whole-body molecular imaging offers a unique diagnostic approach to these disorders. This is particularly true for positron emission tomography/computed tomography (PET/CT) with 18F-flourodeoxyglucose (FDG) which in recent years has become an established tool not only in cancer but also increasingly in infectious and inflammatory diseases. This review outlines current applications of FDG PET/CT in the most common vascular infectious and inflammatory diseases, i.e. vascular graft infections, vasculitis, and deep venous thrombosis (DVT). Keywords: PET, PET/CT, FDG, vascular disease, vascular graft infection, vasculitis, venous thromboembolism.
The use of whole-body imaging with 18F-fluorodeoxyglucose positron emission tomography/ computed tomography (FDG-PET/CT) is increasing in systemic infectious diseases, including fever of unknown origin (FUO), bacteraemia of unknown origin (BUO), and central nervous system infections, since the primary aim is to guide the clinicians towards potential sites of origin for further exploration, and a high sensitivity whole-body assessment is therefore pivotal. The literature on these subjects remains relatively sparse, but the available data and the widespread use in daily clinical practice seem justified in FUO and BUO, while results on CNS infections with systemic components are more equivocal. However, more systematic, well-designed prospective studies in defined patient populations are needed to clarify the controversies, including indications and cost effectiveness, scan parameters, and quantification. Keywords: PET, PET/CT, FDG, infection, fever of unkown origin, bacteraemia, CNS.
Cocaine has been known to inhibit dopaminergic and serotonergic systems. Here, we aimed to study the addictive effects of cocaine on both systems of rats after chronic treatments. Rats were treated with vehicle or cocaine for four months, and the changes of behavior and expressions and activity of dopaminergic and serotonergic systems were assessed. Locomotion was used to estimate the animal behavior. The neuronal imaging of dopamine D2 receptor (D2R) with [11C]raclo- [11C]raclopride/microPET and serotonin transporter (SERT) with [123I]-2-((2-((dimethylamino) methyl) phenyl) thio)-5- iodophenylamine ([123I]ADAM)/gamma scintigraphy was performed for determining the specific striatum/midbrain binding ratios. Animal Magnetic Resonance Imaging (MRI) and immunohistochemistry (IHC) were applied to assess the anatomical changes in the rat brains. The activated locomotion was found for the first ten weeks, and gradually recovered to the baseline. Brain D2R imaging (i.e., [11C]raclopride/microPET) showed the decreased ratio of striatum/midbrain during the study and two weeks post the withdrawal of cocaine treatments. Brain SERT imaging (i.e., [123I]ADAM/gamma scintigraphy) was also found similar to the declined ratio of midbrain/cerebellum. However, animal MRI did not find brain hemorrhage and edema. Notably, the results obtained from IHC showed serious neuronal damage with decreased Tyrosine Hydroxylase (TH)-positive and increased glial fibrillary acidic protein (GFAP)-positive expressions in the critical brain regions. These results demonstrate that the predominant effect of chronic cocaine treatments on the dopaminergic system is more severe than on the serotonergic system as evaluated with the behavioral tolerance, D2R impairment, and dopamine neuron deficit. Keywords: [11C]raclopride, [123I]ADAM, dopamine D2 receptor, glial fibrillary acidic protein, serotonin transporter, tyrosine hydroxylase.
Background: Evaluation of focal liver injury is an important obstacle facing precise liver surgery. We investigated for a correlation between the average ADC of the whole liver and serum liver function tests, and also sought to determine a diagnostic ADC threshold for diagnosing liver injury. Materials and Methods: Diffusion weighted imaging (DWI) and liver function tests were performed on 24 patients with common bile duct (CBD) stones and 20 normal control volunteers. Statistical analyses including Spearman correlation analysis and ROC analysis were performed to determine the ability for the apparent diffusion coefficient (ADC) to predict focal liver injury. Results: The average ADC value of control and CBD stones groups were 1378±93mm2/s and 1084±190mm2/s. The ADC value significantly correlated with serum liver function tests including total bilirubin, direct bilirubin, γ- glutamyltransferase, and alkaline phosphatase measurements (r=-0.573,-0.528,-0.549, and -0.595, P < 0.001). ROC analysis of ADC as a predictor for focal abnormal liver function was performed using a reference standard of serum liver functional tests (1990 Council for International Organizations of Medical Sciences) and demonstrated an area under the curve (AUC) of 0.946. Using an ADC of 1249mm2/s as the threshold value, sensitivity was 79.2% (95%CI 57.8-92.9%) and specificity was 100% (95%CI 83.2-100.0%). Conclusion: Noninvasive diffusion weighted imaging is able to identify focal hepatocellular injury from biliary obstruction. Keywords: Apparent diffusion coefficient, common bile duct stones, diffusion weighted imaging, focal liver injury, functional imaging, magnetic resonance imaging, ROC, sensitivity and specificity.
Conventional clinical imaging plays crucial role in management of TB. Recently, F-18 fluoro-deoxy-glucose (FDG) positron emission tomography/computed tomography (PET/CT) has been widely used as an useful imaging modality in the field of oncology. However, FDG is a glucose analogue and its uptake depends upon the degree of glucose metabolism within the cell. Moreover, literature evidence suggest role of FDG PET/CT in different infectious and non-infectious inflammatory diseases including fever of unknown origin. This review article elaborates emerging role of PET/CT in the management of TB. Keywords: F-18 FDG, PET, Tuberculosis.
Purpose: The unambiguous prostate cancer diagnosis is of high global interest. Magnetic Resonance Imaging (MRI) is a low invasive modality in early stages of tumor diagnosis, especially for cancer detection. The study aim is to synthesize Gd3+ based silica mesoporous nanosphere conjugated with Monoclonal Antibody (Mab C595) and evaluate its ability as nanoprobe for prostate cancer cells detection. Method: Here, a nanoprobe, specifically recognizing in vivo MUC-1 antigen in prostate cancer cells, was synthesized and evaluated. The in vitro studies included cell toxicity, cell binding and immune reactivity assay. MR imaging parameters of this nanoprobe were investigated by MRI. Results: Results showed that this nanoprobe is a selective MUC-1 detector, without any significant cell toxicity. Conclusion: This study confirmed that this nanoprobe is potentially a selective prostate molecular imaging agent for cancer cell detection. Keywords: Mesoporous silica nanosphere, MR imaging, monoclonal antibody C595, MUC-1, prostate cancer detection.
Proton Magnetic Resonance Spectroscopy (1H MRS) of the brain is a versatile technique for the study of brain metabolism and brain function and has found wide applications in biomedical research and clinical diagnosis. Proton MRS is capable of measuring concentrations of brain chemicals, probing cellular energetic mechanism, membrane metabolism, and mitochondrial function, thus allowing us to understand the neuro-pathophysiology of psychiatric disorders including autistic spectrum disorders. The aim of this article is to introduce the MRS techniques and review the recent advances of their applications in autistic disorders. Emphasis is given to the practical use of these techniques and the most important and challenging brain chemicals for autistic disorder including N-acetyleaspartate, glutamate and glutamine, gamma-Aminobutyric acid, and lactate.
PET/CT has had an evolutionary role in Oncology. Gynecological malignancies have been increasing in incidence in the last decades. Delay in diagnosis and management have led to worsening prognosis among the patients. Lowering the threshold in suspecting these tumors, may significantly improve the patients’ overall survival. In this review we will address the role of FDG-PET/CT in diagnosing, staging, assessing the response to therapy and predicting survival in gynecological malignancies, namely endometrial, ovarian and cervical cancer. We will briefly compare the diagnosing ability of PET/MRI to PET/CT. We will address the interesting fact about simultaneously utilizing the Apparent Diffusion Coefficient (ADC) with the Standardized Uptake Value (SUV) in hybrid MRI imaging and we will also discuss about the role of PET/MRI in diagnosing primary and recurrent gynecological malignancies.
Semantic Dementia (SD) is classified as a type of Frontotemporal Lobar Degeneration (FTLD) characterized by progressive impairment of conceptual knowledge, accounting for approximately 30% of cases of FTLD. Clinical symptoms and brain Magnetic Resonance (MR) imaging are helpful to reach the diagnosis in the advanced stage, but brain positron emission tomography with [18F] Fluoro-2-Deoxy-D-Glucose (FDG-PET) might be useful to evaluate and distinguish the early stage of SD. This review summarizes 9 studies using FDG-PET with either SPM or three-dimensional stereotactic surface projection statistical software to elucidate the features of SD. The main hypometabolic lesions associated with SD were located in the bilateral temporal lobes. The so-called core lesions were predominantly located in the left and anterior and lower parts of the temporal lobe. Hypometabolism on FDGPET was more extensive than atrophy detected on MR imaging in the temporal lobes and especially involved the bilateral orbitofrontal areas, right caudate nucleus, and insula. FDG-PET is very helpful to diagnose SD in the early to advanced stages.
Magnetic Resonance Imaging (MRI) is a mature methodology that has been widely used for the evaluation of brain gliomas. Conventional MR imaging can provide morphometric characterization of gliomas, whereas proton Magnetic Resonance Spectroscopy (MRS) provides metabolite information for gliomas non-invasively in vivo. In the application to brain gliomas, proton MRS plays an important role in diagnosis, differential diagnosis, classification, evaluation, treatment planning and prognostic evaluation, and monitoring response to therapy. Over the past more than three decades, both the MRS techniques and their applications in brain gliomas have experienced remarkable proliferation. The aim of this article is to introduce the technique, the metabolites and review its clinical applications in brain gliomas.
Crohn's Disease (CD) is a chronic inflammatory bowel disorder which can lead to complications like fistulas, strictures and abscesses. It is difficult to differentiate between chronic fibrotic and acute inflammatory processes with current non-invasive and invasive methods. FDG-PET/CT might help to identify active inflammatory processes and morphological information via one examination. It is a case report of a 22 year old woman diagnosed with CD who experienced an abscess of the left psoas muscle after few years which had to be drained. In 2011, she again complained about left side abdominal pain. This case underlines the usefulness of a combined PET/CT study for identifying active inflammatory processes common on patients suffering from Crohn’s disease. Generally it would be optimal to combine the PET and a diagnostic quality CT-E into a single session.
The use of 2-deoxy-2-[18F] fluoro-D-glucose (FDG) and positron emission tomography/ computed tomography (PET/CT) is increasing rapidly – and the list of emerging and evolving applications is everexpanding in a multitude of clinical settings. In this anniversary review celebrating four decades of FDG, we will outline an overview of the present status of FDG imaging with emphasis on clinical implementation in the main indications of FDG-PET/CT, i.e. neurology and psychiatry, oncology, cardiovascular diseases, and infectious and inflammatory diseases, including some general considerations towards clinical benefit and potential future directions. Keywords: FDG, PET, PET/CT, PET/MRI, cardiology, clinical drug development, infection, inflammation, pediatrics, neurology psychiatry, oncology, radiation therapy planning.
Translational projects frequently test agents by intravenous injection into small animals. One problem is that it is usually uncertain exactly how successful each injection is at time of administration. This leads to high variation in measurements and necessitates the use of larger groups of animals. To circumvent this problem, we introduce a novel near infrared imaging method to determine injection success in adult and neonatal mice. By co-injecting a near infrared fluorophore AngioSense 750 with a therapeutic agent, the location of near infrared fluorescence can be used to determine injection quality. To test this method, an Adenoviral (Ad) vector expressing luciferase was co-injected with AngioSense at different sites in adult and neonatal mice. When injection was successful, the near infrared fluorophore entered into the bloodstream and spread throughout the body of the animal and vector-mediated luciferase activity was observed in the liver. When intravenous injection was a failure, the near infrared and subsequent luciferase signals remained localized at the injection site. This work has been performed with adult and neonatal mice using an adenoviral vector, but it can be translated to other small animals or small anatomic sites for any therapeutic or basic science application. Keywords: Adenovirus, intravenous injection, systemic injection, near infrared fluorescence imaging, contrast agent.
A protocol to load perfluoro-crown-ether (PFCE) nanoemulsion directly into yeast-derived glucan particles (GPs) was developed. It was observed that the PFCE encapsulation did not affect the 19F-MRI properties of the nanoemulsion that is currently in clinical trials. GPs loaded with PFCE nanoemulsion were taken up avidly by murine macrophages in vitro, resulting in a cellular uptake 150 % higher than the not GPs-entrapped nanoemulsion. Accordingly, a corresponding improvement in the 19F-MRI detection of the labelled cells can be obtained. The high biotolerability and versatility of GPs, make these microcarriers a promising option for designing of improved in vivo cellular imaging protocols. Keywords: 19F-MRI, cellular imaging, glucan particles, macrophages, theranosis, perfluorocarbons.
As in many other infectious diseases 2-deoxy-2-[18F] fluoro-D-glucose (18F-FDG) positron emission tomography (PET) combined with computed tomography (CT) (18F-FDG-PET/CT) has shown obvious potential in cardiovascular infections, although several issues remain unclarified with regard to acquisition and patient preparation protocols. Overall, 18F-FDG-PET/CT should be considered an important complementary diagnostic technique in infectious endocarditis, and cardiac device related infections, especially for extracardiac disease state. Also, monitoring of the metabolic response to antibiotics should be considered a promising indication, and the high negative predictive value of 18F-FDG-PET/CT is also of great clinical relevance. The purpose of this work was to present the current evidence regarding the role of 18F-FDGPET/ CT in infectious endocarditis, extracardiac complications, and cardiac implantable electronic devices. Keywords: 18F-FDG-PET/CT, infectious endocarditis, cardiac implantable electronic device infection, left ventricular assist devices.
Background: Post-Traumatic Stress Disorder (PTSD) is an anxiety disorder in response to a major traumatic event. Higher levels of trauma may be associated with more deficits in the brain SERT availability. We investigated the in vivo dynamitic change of SERT availability in the brain of PTSD rat with increasing severity of disease with 4-[18F] ADAM PET which reflects the SERT availability. Methods: Pavlovian fear conditioning model of PTSD was used in this study. Sprague-Dawley rats (N=6/group) were conditioned with 3, 6 and 10 tone-shock pairings at 1 min intervals, and the freezing responses was measured as the percentage of time spent in freezing during 1 min interval. Static PET imaging was performed in PTSD animals after administration of 2-(2-amino-4-[18F] -fluorophenylthio) benzylamine (4-[18F]-ADAM) (150 µCi/100µl, i.v.). One day later, the brains were removed and grounded for the quantitation of AMPA receptor trafficking. Results: The conditioned 6 or 10 tone-shock pairings exhibited higher level of cue-evoked freezing behavior compared with 3 tone-shock pairings groups (p< 0.01). PET results showed that a positive correlations between SERT availability in the brain regions including amygdala, caudate/putamen, hippocampus, hypothalamus, midbrain, pituitary, frontal cortex and cerebellum in the groups of mild or moderate PTSD but a negative correlation in the severe group. The phosphorylation of GluR1 at Ser831 which were subunits of AMPA was dramatically increased in the amygdala and hippocampus of severe group compared with control group. Conclusions: The results support that 4-[18F]-ADAM PET could be used to monitor the alteration of SERT availability associated with PTSD severity. Keywords: PTSD, 4-[18F]-ADAM, serotonin transport.
Positron emission tomography (PET) with 18-fluorodeoxyglucose visualizes hypermetabolic disease processes by metabolic trapping. Since its inception in the late 1970s the method has gained widespread use, primarily in oncology for tumor detection, staging and therapy evaluation. Within the last decades it has also become relevant in the field of inflammation, as this too is characterized by focal hypermetabolism. In this review we report on the current literature (22 studies) on the application of PET and its feasibility in inflammatory bowel disease (IBD) compared with other modalities, e.g. endoscopy, in both the adult and pediatric population. With PET, the entire gastrointestinal tract including transmural and extra-intestinal disease can be visualized in one single examination. Almost without contraindications, PET can be used to diagnose IBD with high sensitivity and specificity, for response evaluation and characterizing of strictures. Using new quantitative techniques, a global disease score which correlates well with current disease indices and endoscopic findings can be determined to measure and monitor the extent and severity of disease. Keywords: 18-fluorodeoxyglucose positron emission tomography, diagnostic modalities, global disease assessment, inflammatory bowel disease (IBD), therapy response, pediatrics.
Background: Tc-99m labeled Glucaric Acid (Tc-GA) and In-111 labeled human fibrinogen (In-HF) were used to demonstrate reduction in myocardial infarction and microvascular injury in rabbit preconditioned ischemic hearts. Methods: New Zealand White rabbits were subjected to preconditioning or non-preconditioning ischemic myocardial injury. Reperfusion was established after 45 min of circumflex occlusion and then Tc-GA and In-HF were injected intravenously. Anteroposterior gamma images were acquired for 4 hours. Perfusion defects, histochemical infarct size and radiotracer uptake were determined. Results: In vivo and ex vivo images were consistent with the gamma scintillation counting data. Minimal GA and fibrin depositions were seen in preconditioned ischemic hearts (3.78± 10.7 and 0 % of total myocardial area respectively) whereas the areas delineated by GA and fibrin deposition in non-ischemic preconditioned hearts were larger (61.9± 34.5 and 60.0± 32.7%). Infarct size of preconditioned ischemic hearts was 4.6±1.9 % of the left ventricle, whereas that of non-preconditioned ischemic hearts was 24.1±5.9% (P <0.01) assessed by histochemical technique. Infarct size from imaging was approximately 2.5 times that of the histochemical assessment. The regions of perfusion defect were similar (23.3±4.1 vs 26.5+8.5% respectively). Images of Tc-GA uptake and In-HF deposition were consistent with histochemical and radiotracer uptake data indicating minimal myocardial injury in preconditioned ischemic hearts even though areas of perfusion defect were similar. Conclusion: The data indicates that ischemic precondition not only preserved myocyte viability but also reduced microvascular injury. Keywords: Gamma imaging, histochemical infarct assessment, myocardial ischemic preconditioning, myocardial microvascular integrity, radiotracer.
