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Molecular imaging and neural networks in impulse control disorders in Parkinson's disease.

Impulse control disorders (ICDs) may arise in Parkinson's disease (PD) in relation to the use of dopamine agonists (DA). A dysfunction of reward circuits is considered the main underlying mechanism. Neuroimaging has been largely used in this setting to understand the structure of the reward system and its abnormalities brought by exogenous stimulation in PD. Dopaminergic changes, such as increased dopamine release, reduced dopamine transporter activity and other changes, have been shown to be a consistent feature of ICDs in PD. Beyond the striatum, alterations of prefrontal cortical function m

Molecular imaging in sporadic Alzheimer's disease populations and those genetically at risk.

The time course and order of the pathological-physiological processes in Alzheimer's disease (AD) are still under investigation and it is expected that molecular imaging will provide important insight into early brain pathology. Multi-tracer positron emission tomography studies visualizing fibrillar amyloid, inflammatory changes including astrocytosis and activation of microglia as well as cerebral glucose metabolism indicate that AD pathological processes are initiated and ongoing decades before the onset of cognitive symptoms. Therefore, prevention might be a new promising target for AD ther…

Imaging dynamic molecular signaling by the Cdc42 GTPase within the developing CNS.

Protein interactions underlie the complexity of neuronal function. Potential interactions between specific proteins in the brain are predicted from assays based on genetic interaction and/or biochemistry. Genetic interaction reveals endogenous, but not necessarily direct, interactions between the proteins. Biochemistry-based assays, on the other hand, demonstrate direct interactions between proteins, but often outside their native environment or without a subcellular context. We aimed to achieve the best of both approaches by visualizing protein interaction directly within the brain of a live

PET molecular imaging to investigate higher brain dysfunction in patients with neurotrauma.

INTRODUCTION: Many neurotrauma patients suffer from higher brain dysfunction even when focal brain damage is not detected with MRI. We perfo … cose metabolism and cBZD-R distribution when they suffered from cognitive deficit. CONCLUSION: PET molecular imaging was useful for depicting the cortical dysfunction of neurotrauma patients even when morphological change was not apparent. This method may be promising in clarifying the pathophysiology of higher brain dysfunction of patients with neurotrauma, but w …

Molecular imaging of small animals with fluorescent proteins: from projection to multimodality.

Fluorescent proteins (FPs) have been widely adopted in cell research for protein trafficking and reporter gene expression studies, as well as to study other biological processes. However, biological tissue has high light scattering and high absorption coefficients of visible light; hence, using FPs in small animal imaging remains a challenge, especially when the FPs are located deep in the tissue. In small animals, fluorescence molecular imaging could potentially address this difficulty. We constructed fluorescence molecular imaging systems that have two modes: a planner mode (projection imagi…

Multispectral molecular imaging of capillary endothelium to facilitate preoperative endovascular brain mapping.

OBJECT: Brain mapping aims to localize neurological function to specific regions of the human brain. Preoperative endovascular brain mapping … vascular occlusion. Gross regional selectivity of the imaging probe was documented by multispectral molecular imaging of intact brains, with discrete localization and endothelium-directed targeting validated by histological examination. CONCLUSIONS: The authors have demonstrated the first molecular endothelium-targeted approach to PEBM that does not require manipu …

Investigating the dopaminergic synapse in vivo. I. Molecular imaging studies in humans.

Dopaminergic synaptic function may be assessed either at the presynaptic terminal or at the postsynaptic binding sites using molecular in vivo imaging methods. Apart from the density of binding sites, parameters such as alterations in dopamine synthesis, dopamine storage or dopamine release can be quantified either by application of specific radiotracers or by assessing the competition between the exogenous radioligand and endogenous dopamine. Investigations of humans in both clinical and experimental settings have yielded evidence that disturbances of dopaminergic function may be associated w

A Practical Guide to PSMA PET Radiopharmaceuticals for Prostate Cancer Imaging, From the AJR Special Series on Molecular Imaging.

Since the first FDA approval of a PSMA-targeted PET radiopharmaceutical ([68Ga]Ga-PSMA-11) in 2020, PSMA PET/CT has rapidly become the standard of care for certain indications in prostate cancer imaging. Subsequently, the FDA also approved [18F]DCFPyl and [18F]rhPSMA-7.3. Although these small-molecule agents share an amino acid binding domain specific to the PSMA molecule, they differ in key ways (e.g., radioisotope physical and chemical properties, ligand structure), with potential clinical implications regarding synthesis, distribution, and imaging characteristics. For example, differences i

Microviscosity-gated excited-state partitioning in a NIR-II molecular rotor for disease imaging and imaging-guided photothermal therapy.

Microviscosity is an underexploited pathological cue that can be harnessed to regulate excited-state energy dissipation in organic near-infrared II (NIR-II, 1000-1700 nm) fluorophores. Here we introduce a twisted intramolecular charge transfer molecular rotor that uses microviscosity to gate radiative versus nonradiative decay, delivering a fluorescence "off" state in low-viscosity environments and a weak-but-sufficient NIR-II fluorescence turn-on in viscosity-elevated pathology while keeping nonradiative dissipation dominant for photothermal heating. A tunable donor-π-acceptor library was syn

Molecular imaging of endocrine neoplasms with emphasis on 18F-DOPA PET: a practical approach for well-tailored imaging protocols.

6-[18F]-L-fluoro-L-3, 4-dihydroxyphenylalanine (18F-DOPA) PET/CT can be a useful tool for the detection of different neuroendocrine tumors (NETs). The main determinants of 18F-DOPA uptake and retention by NETs are related to expression of LAT1/LAT2 transporters, expression and activity of AADC and biochemical phenotype, all being intimately inter-connected to their embryological origin. In order to improve sensitivity of 18F-DOPA PET, it is of main importance to perform indivisualized imaging protocols across primaries. This review provides a practical approach for performing well-tailored ima

Molecular imaging of cartilage damage of finger joints in early rheumatoid arthritis with delayed gadolinium-enhanced magnetic resonance imaging.

OBJECTIVE: To assess cartilage glycosaminoglycan content and cartilage thickness in the metacarpophalangeal (MCP) joints of patients with early rheumatoid arthritis (RA) and healthy volunteers. METHODS: After review board approval and informed consent were obtained, 22 subjects were prospectively enrolled (9 patients with early RA [7 women and 2 men with a mean ± SD age of 49 ± 13 years; range 25-68 years] and 13 healthy volunteers [10 women and 3 men with a mean ± SD age of 51 ± 12 years; range 25-66 years). In a total of 44 MCP joints of the index and middle fingers, measurements of cartila

The accumulation mechanism of the hypoxia imaging probe "FMISO" by imaging mass spectrometry: possible involvement of low-molecular metabolites.

(18)F-fluoromisonidazole (FMISO) has been widely used as a hypoxia imaging probe for diagnostic positron emission tomography (PET). FMISO is believed to accumulate in hypoxic cells via covalent binding with macromolecules after reduction of its nitro group. However, its detailed accumulation mechanism remains unknown. Therefore, we investigated the chemical forms of FMISO and their distributions in tumours using imaging mass spectrometry (IMS), which visualises spatial distribution of chemical compositions based on molecular masses in tissue sections. Our radiochemical analysis revealed that m

Molecular imaging of brain lipid environment of lymphocytes in amyotrophic lateral sclerosis using magnetic resonance imaging and SECARS microscopy.

This paper highlights some of the key technologies of using two innovative molecular imaging modalites, magnetic resonance imaging (MRI) and nonlinear optical microscopy, for imaging intravenously injected ultra small paramagnetic iron oxide nanoparticles cross linked with antibodies (CLUSPIO) in the amyotrophic lateral sclerosis (ALS) experimental model in vivo or ex vivo, respectively. Intensive efforts have been made in investigating the causes of abnormalities in lipid metabolism, monitored in some neurodegenerative disorders systems. It has been shown that an abnormal accumulation of some…

Cross-Species Molecular Imaging of Bile Salts and Lipids in Liver: Identification of Molecular Structural Markers in Health and Disease.

The liver is the primary organ involved in handling of bile salts, a class of amphipathic molecules with signaling activities as well as desired and detrimental detergent actions. To allow in-depth investigation of functions of bile salts in healthy and diseased liver, the spatial distribution of bile salt species within the liver needs to be studied. Therefore, the aim of our study was to determine hepatic bile salt distribution and identify specific lipid markers that define the structural elements of the liver. Matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI

Ex-vivo Imaging of Upper Tract Urothelial Carcinoma Using Novel pH Low Insertion Peptide (Variant 3), a Molecular Imaging Probe.

OBJECTIVE: To improve visualization of upper tract urothelial carcinomas. Previous studies using the novel pH low insertion peptide (pHLIP) variant 3 (Var3) conjugated to indocyanine green (ICG) have demonstrated high sensitivity and specificity for imaging of bladder urothelial carcinoma. Here, we describe a novel approach for the imaging of upper tract urothelial carcinomas using ICG-Var3 pHLIP. METHODS: Twelve ex-vivo upper urinary tract specimens were irrigated with ICG-Var 3 pHLIP for 15 minutes and then examined using a white light laparoscopic camera followed by near infrared fluoresce

Molecular Imaging of Sirtuin1 Expression-Activity in Rat Brain Using Positron-Emission Tomography-Magnetic-Resonance Imaging with [18F]-2-Fluorobenzoylaminohexanoicanilide.

Sirtuin 1 (SIRT1) is a class III histone deacetylase that plays significant roles in the regulation of lifespan, metabolism, memory, and circadian rhythms and in the mechanisms of many diseases. However, methods of monitoring the pharmacodynamics of SIRT1-targeted drugs are limited to blood sampling because of the invasive nature of biopsies. For the noninvasive monitoring of the spatial and temporal dynamics of SIRT1 expression-activity in vivo by PET-CT-MRI, we developed a novel substrate-type radiotracer, [18F]-2-fluorobenzoylaminohexanoicanilide (2-[18F]BzAHA). PET-CT-MRI studies in rats d

Highlights lecture EANM 2016: "Embracing molecular imaging and multi-modal imaging: a smart move for nuclear medicine towards personalized medicine".

The 2016 EANM Congress took place in Barcelona, Spain, from 15 to 19 October under the leadership of Prof. Wim Oyen, chair of the EANM Scientific Committee. With more than 6,000 participants, this congress was the most important European event in nuclear medicine, bringing together a multidisciplinary community involved in the different fields of nuclear medicine. There were over 600 oral and 1,200 poster or e-Poster presentations with an overwhelming focus on development and application of imaging for personalized care, which is timely for the community. Beyond FDG PET, major highlights inclu

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… As a community, we are paralleling the explosion in different facets of medicine including immunotherapy and radionuclide therapy through implementation of multimodal molecular imaging diagnostic approaches that will not only make better use of these powerful therapies but also, in the future, help us … Molecular imaging in non-oncology areas is clearly expanding and in some cases ahead of drug development programmes, and thus promises to be highly valuable in the clinical implementation of the drugs in such programmes. …

Visualizing the molecular landscape of skin: applications and perspectives of mass spectrometry imaging.

Mass spectrometry imaging (MSI) has emerged as a powerful tool in dermatological research due to its high sensitivity, label-free detection, and ability to simultaneously analyze multiple molecular species. This review systematically summarizes recent advancements in the application of MSI for visualizing both endogenous metabolites/biomacromolecules and exogenous compounds in the skin. Firstly, the basics of MSI are introduced, including the different ionization sources and the general workflow of MSI experiments. Then, the applications of MSI in skin physiology and metabolism analysis and id

Precision at the Margin: Innovations and Challenges in Intraoperative Molecular Imaging for Thoracic Surgery.

Tumor localization during pulmonary surgery has become increasingly challenging with the earlier detection of smaller and smaller lung nodules. Concomitantly, minimally invasive surgical (MIS) techniques have been increasingly adopted within the field of thoracic surgical oncology. Surgeons face growing challenges not only with locating these small tumors, but also with immediate margin assessment, reduced tactile feedback, and nodal assessment. Intraoperative molecular imaging (IMI) has emerged as a promising adjunct to address these challenges by enabling real-time visualization of malignant…

Utility of multimodal molecular imaging in the diagnosis and decision-making in arterial diseases.

Arterial diseases are prevalent in the general population, particularly in the elderly, and they are among the main causes of morbidity and mortality worldwide. Nuclear imaging is a useful tool in diagnosis and follow-up in different areas of medicine, and over the last 2 decades, these study modalities have become more relevant in the field of angiology and vascular surgery due to their potential benefit in the interpretation of pathophysiological mechanisms associated with the natural history and severity of diseases that affect the circulation such as vasculitis, degenerative aortic aneurys