Small Animal Imaging

Infinity is the preclinical imaging research facility of Ghent University, providing multimodality-imaging services to national and international customers. It is a consortium of two major research groups: Medisip and the Laboratory for Radiopharmacy. A skilled and experienced scientific staff is running Infinity. Professors Christian Vanhove, Stefaan Vandenberghe, Filip De Vos and Roel Van Holen work together to streamline the research at Infinity. Additionally, professor Christian Vanhove is also responsible for the day-to-day functioning of the lab and the coordination of the partner research, either from within Ghent University, from private companies or from other universities. The major research domains of Infinity are neuromodulation (deep brain stimulation and trans-cranial magnetic stimulation), the use of imaging biomarkers to provide better tumor characterization, stress of the endoplasmatic reticulum (er stress), cardiovascular research to get a better understanding of the formation of aneurysms and plaque, and the development of ‘theranostic’ approaches by combining diagnosis and therapy.

But Infinity is about more than providing service to partners. The lab is actively involved in the Multidisciplnary Research Platform on Inflammation and Immunity, called Group-ID. In 5 years time, Group-ID aims to be an international center of excellence in inflammation research, continuously attracting the best students and postdocs, have sufficient independent funding from the government and industry and become a core center of translational research in medicine.

Current research

MR biomarkers for cognitive training in mild traumatic brain injury in rats

Traumatic brain injury (TBI) after a fall or car accident can lead to cognitive impairment which limits patients in everyday life. To better understand the underlying pathophysiology, TBI is induced in rats, and the brain is imaged with diffusion MRI, a technique capable of imaging the neural network. In a follow up study the rats will receive cognitive training, similar to training protocols in human patients in order to image the neuroplasticity of the brain. By fitting the diffusion signal to white matter models the neural network can be revealed, and the defects and recovery can be followed up in time. A complementary histological analysis will correlate the biomarkers found in the MRI experiments to the biological basis.

Figure 1: Cognitive training in the Bussey Saksida touchscreen chamber

Contact: Kim Braeckman

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Combining optogenetics, chemogenetics, intracranial electroencephalography and functional magnetic resonance imaging to investigate abnormal functioning of brain networks during epileptogenesis

Epilepsy is a disease characterized by recurrent seizures. It is difficult to predict which patients will respond to the different treatment options, because little is known about the development of epilepsy and the neural networks that might be involved. With functional magnetic resonance imaging (fMRI) whole-brain activity can be visualized, functionally connected brain regions can be identified and functional networks can be constructed. These networks can be characterized using graph theory measures. Optogenetics and chemogenetics are new techniques that allow very specific activation or inhibition of neurons, using light and specific drugs respectively. Optogenetics will be used to induce seizures during scanning, while chemogenetics will be used to try to modulate the epileptic network changes and to suppress spontaneous epileptic seizures.

(adapted from: Harris, N. G., et al. “Disconnection and hyper-connectivity underlie reorganization after TBI: A rodent functional connectomic analysis.” Experimental neurology 277 (2016): 124-138.)

Contact: Emma Christiaen

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Associated research

Tracing xylem-transported 11C-labelled CO2 in trees: importance and contribution to the carbon metabolism

Positron-emitting radionuclides like 11C, 13N and 18F are long used in human and animal studies and have led to major breakthroughs. In this respect, positron emission tomography (PET) imaging is receiving increased interest in the field of plant sciences. More specifically, molecules like 11CO2 or 18FDG can, for example, be used as a tool for phenotyping genetically engineered plants and as a new strategy to measure plant responses to drought in a changing climate. The latter being an active and topical research area, yet many questions remain unanswered. In order to understand plant survival and mortality during drought it is crucial to gain more insight into the different mechanisms contributing to both the carbon budget and hydraulic functioning of trees. Hereby, the role of internally transported CO2 in xylem of trees and the associated woody tissue photosynthesis are often overlooked. Our group will focus on these aspects by tracing radioactive 11CO2 in xylem of trees using positron emission tomography (PET) reinforced with magnetic resonance imaging (MRI) for structure-related information. By examining different tree species, subjected towards changing atmospheric conditions, essential insights will be acquired to understand how a given environment will affect plant physiological processes and growth in vivo.

Figure 1: Experimental set-up for plant-PET imaging Figure 2: Positron autoradiogram showing
the distribution of xylem-transported
11CO2 in an excised poplar leaf [Bloemen et al., 2015]

Contact: Jens Mincke

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18F and 99mTc labeled bile acid analogues to study (altered) hepatobiliary transporter function

Numerous drugs are substrate or inhibitor of hepatobiliary transport mechanisms. This can lead to drug induced liver injury. Therefore, it is important to assess these possible interactions from early on during drug development.

Figure 1: Overview of the most important bile acid transporters. Organic Anion Transport Protein 1a/1b (Oatp1a/1b), Sodium Taurocholate Cotransporting Protein (NTCP) are the most important uptake transporters. Multidrug Resistance Protein 2 (Mrp2) and Bile Salt Export Pump (Bsep) are the most important efflux transporters

Aim: synthesis of radiolabeled substrates (bile acid analogues) which can be used for molecular SPECT and PET imaging. This is a non-invasive in vivo method to allow visualization and quantification of normal and disturbed hepatobiliary transport. The use of a non-invasive method can significantly reduce the cost for preclinical drug development.

Figure 2: Dynamic USPECTII-CT (MILabs) acquisition of 37 MBq of a technetium labeled bile acid analogue. After injection, the tracer is taken up from the blood into the hepatocytes, and are then transported to the gallbladder and intestine. Aditionally, the tracer is cleared by the kidneys. 120 frames; 1 min/frame; 4 bed positions

Contact: Stef De Lombaerde, Sara Neyt

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The impact of accelerated High Frequency repetitive Transcranial Magnetic Stimulation (HF-rTMS) on the serotonergic and dopaminergic system in a rat model of depression

Accelerated HF-rTMS targeted to the DLPFC is a new therapeutic strategy that has shown to be successful in the treatment of major depression in humans. It makes use of an intensified rTMS protocol where both the number of pulses/session and the number of daily sessions have been drastically increased compared to conventional rTMS protocols. Hereby the treatment duration is shortened from several weeks to only four days and beneficial clinical results are obtained much faster. Despite its usefulness, up to now little is known about the basic molecular mechanisms that support these therapeutic effects.

By using the PET-radiotracers [18F]altanserin, [11C]raclopride and [11C]DASB, this study tries to investigate the impact of accelerated HF-rTMS on respectively the availability of the serotonin 5-HT2a receptor, the dopamine D2 receptor and the serotonin transporter in a rat model of depression. Imaging these neurotransmitter systems, which both play an important role in the pathology of depression, can make a substantial contribution to unravel the neurological mechanisms involved in (accelerated) HF-rTMS and to further optimize the stimulation protocol.

Contact: Nick Van Laeken, Glenn Pauwelyn

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Development of LAT1-specific 18F amino acid PET tracers for the discrimination between low and high grade glioma

The use of O-(2-[18F]fluoroethyl)-L-tyrosine (18F-FET) as a tumor PET tracer has several limitations including the relatively low affinity for the L-type amino acid transporter (LAT1).

Aim: Synthesis of [18F]-fluoroalkylated phenylalanine analogues with higher affinity for the LAT1 transporter. A LAT1 specific amino acid PET tracer would
allow grading between low and high grade glioma and result in a faster detection of tumor progression.

Development of LAT1-specific 18F amino acid PET tracers

Contact: Jeroen Verhoeven

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Discriminating high-grade glioma from radiation necrosis in rats using kinetic modeling

Discriminating high-grade glioma from radiation necrosis in rats using kinetic modeling and graphical analysis with three different PET tracers: 18F-fluoromethylcholine (FCho), 18F-fluoroethyltyrosine (FET) and 18F-fluorodeoxyglucose (FDG)

Contact: Julie Bolcaen

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Effect of Cx-mimetic peptide administration on breast cancer brain metastasis development

Brain metastasis occurs in 10-15% of the breast cancer patients and entails a strong component of tumor-host interactions. Recent evidence suggests a crucial role for transmembrane connexin (Cx) proteins, primarily Cx43, in the tumor-host interactions by forming intercellular communication pathways. GAP27 is a Cx-mimetic peptide that inhibits Cx-based intercellular communication.
We examine the effect of GAP27 on the initial seeding and subsequent colonization of the brain by using a xenograft model for rat brain metastasis that allows follow-up by molecular magnetic resonance imaging (MRI). The MDA-MB-231br/EGFP breast cancer cell line was used for this purpose

Contact: Valerie De Meulenaere

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Past research

Neural circuit mapping using simultaneous DBS-fMRI and opto-fMRI

Optogenetics is a new method that uses a combination of optical and gene technologies to manipulate a specific group of neurons with an unprecedented spatial, temporal and cellular specificity. This is reflected in our results since the fMRI-response maps demonstrate a far more selective response to light stimulation as opposed to electrical stimulation.
(DBS = Deep Brain Stimulation or electrical stimulation; opto = optogenics or light stimulation)

Contact: Nathalie Van Den Berge

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Fast dynamic SPECT

In-vivo micro Single Photon Emission Computed Tomography, or µSPECT, is a functional imaging technique that can provide sub-mm spatial resolution by using pinhole technology. The µSPECT system installed at Infinity (MILabs U-SPECT-II) uses 75 pinholes focused on the same part of the field-of-view, resulting in sub-mm with relatively high sensitivity. This allows for fast dynamic µSPECT to visualize for example hepatobiliary transport using Tc-99m labeled mebrofenin.

Figure 1: Coronal and sigittal slice of SPECT-CT fusion

Contact: Chris Vanhove

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In-vitro analysis of extracted teeth

Micro Computed Tomography, or µCT, is an anatomical imaging technique that can provide three-dimensional images at very high spatial resolution. It is an imaging technology that can help in precise, highly accurate, and non-destructive in vitro analysis of teeth.

Figure 1: In-vitro analysis of extracted teeth


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Evaluating bone structure surrounding dental implants

Although histology has proven to be a reliable method to evaluate the ossoeintegration of a dental implant, it is costly, time consuming, destructive, and limited to one or few sections. Micro Computed Tomography, or µCT, is fast and delivers three-dimensional information, but this technique has not been widely used and validated for histomorphometric parameters yet. This study compared µCT and histomorphometry by means of evaluating their accuracy in determining the bone response to two different implant materials.

Figure 1 : Figure 2 :

Contact: Chris Vanhove

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Continuous infusion micro positron emission tomography

Micro Positron Emission Tomography, or µPET, is a functional imaging technique that provides very high sensitivity; ideal to perform dynamic studies. Observing metabolic changes during dynamic µPET is challenging. Injecting a single bolus of the radiotracer implies the need of decay correction. Due to the decrease in radiotracer concentration over time, image quality will decrease in late frames of the dynamic µPET acquisition. By using continuous infusion of the radiotracer subtle or fast changes in the metabolism can be observed, with equal image quality over the complete duration of the dynamic µPET acquisition. Rat brain stimulation experiments have been investigated using this technique.

Figure 1 : Before stimulation Figure 2 : After stimulation Figure 3 : Activity concentration over time

Contact: Chris Vanhove, Vincent Keereman

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Visualization of the rat somatosensory network

Functional magnetic resonance imaging, or fMRI, is an imaging technique to investigate neuronal activation. It is well known that non-noxious electrical stimulation of the rat forepaw leads to neuronal activation of the somatosensory network. Neuroimaging studies have been performed to visualize the entire rodent somatosensory network, especially the subcortical regions. A data-driven technique (Independent Component Analysis, ICA) was used to identify the somatosensory network.

Figure 1 : Visualization of the rat somatosensory network.

Contact: Chris Vanhove

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Molecular MRI in early radiation injury detection

With conventional magnetic resonance imaging, radiation injury in healthy tissue is only visible at a late stage. Its sensitivity is too small to allow molecular imaging. However, labeling of superparamagnetic particles, e.g., micron-sized particles of iron oxide (MPIOs) with highly specific antibodies, can circumvent this issue. Using this molecular MRI technique, we investigate the early signs of radiation injury, focusing on inflammation-related intravascular molecules.

Figure 1 : MPIO-antibody conjugation Figure 2 : T2* weighted images for ICAM-MPIO experiments

Contact: Benedicte Descamps

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