QCPU Room 1619

Laboratory Scientists: Dr. Elahe Alizadeth

Small-Animal Nuclear Imaging lab at the Queen’s Cardio Pulmonary Unit (QCPU) was launched in late 2018 under the skilled direction of a PhD Adjunct Professor, Dr. Elahe Alizadeh. Our laboratory is fully equipped to handle radiation with all the appropriate permits, safety equipment and shielding. Dr. Alizadeh will be happy to help consult researchers on their best options for research and handle the selection, purchase and handling of radiation. This lab has housed a new tri-modality state-of-the-art imaging platform (VECTor⁴CT) from MILabs (Utrecht, Netherlands), which is a high-resolution ultra-fast low-dose µCT/PET/SPECT scanner to use for small-animal preclinical investigations.

“Designed as a scalable all-in-one platform, each individual modality of VECTor⁴CT – whether X-ray CT, PET or SPECT – offers performance beyond the capabilities of any other preclinical imaging system in terms of image quality and in-vivo imaging functionality.”

VECTor⁴CT system (from MILabs; Netherlands) is an extremely user-friendly, fully integrated multimodal SPECT, PET and CT imaging technology that provides uniform ultra-high resolution for Positron Emission Tomography (PET) and Single Photon Emission Computed Tomography (SPECT). With 0.25 mm SPECT and 0.75 mm PET resolution, nuclear imaging performance is currently approaching physical limits, set by the positron range for PET. Complemented by an easy operation micro-CT in a multi-modal platform, preclinical imaging with VECTor⁴CT is guided by an intuitive and user-friendly operation to ensure highly efficient workflows, including PET, SPECT and CT imaging of small animals with a single dose of anesthesia and without transfering animals between different modalities. Moreover, VECTor⁴CT is equipped with BioVet system (m2m Imaging Corp., Cleveland, OH, USA) which is a specialized monitoring system, used for physiological event triggering and animal monitoring. It is designed to monitor and trigger from three standard channels: Respiration, Temperature and ECG signals.

Vector 4CT nuclear imaging

Research Applications

VECTor⁴CT enables multi-isotope, simultaneous SPECT and PET imaging at uniform and high resolution (0.25 mm for SPECT and < 0.75 mm for PET). The advantages of using VECTor includes the reduction of study times as well as decrease in the number of animals required for a study; most importantly, the SPECT and/or PET images are perfectly registered in space and time, providing instantaneous information about two distinct radiopharmaceuticals under the same physiological conditions. VECTor⁴CT is a valuable tool in many areas of research including:

Cardiovascular and Heart in vivo Studies

Powerful ability to overcome challenges that requires a high temporal / spatial resolutions, as well as perfect cardiac- and respiratory-gating techniques like:

o The fast motion beating heart (up to 400 bpm in rats and 600 in mice)

o The microscopic dimensions of the coronary vessels

o Low blood flow in these vessels

Cancer Research

Focused ability to visualize small structures and small heterogeneous processes in tumors.

Preclinical Imaging for Drug Discovery and Development

Gated Imaging

Cardiac- and Respiratory-gated techniques to capture anatomical, functional and molecular data from a moving target: visualizing 3D and 4D images of moving organs like heart and lungs

Neuroscience

Studying brain function (in healthy aging and as affected by diseases including Parkinson’s, Dementia and Alzheimer’s).

Development and Validation of Novel PET-Tracer Probes

Developing novel radiopharmaceuticals combining both diagnostic / therapeutic capabilities

Imaging Calcified Tissues

Namely bone and tooth for characterization of orthopaedic implants (parameters for the Trabecular Bone / Cortical Bone) and vascular calcification (calcium deposit in blood vessels).

Enhanced-Contrast MicroCT

In vivo imaging technique to measure soft tissues cardiac structure and function

o Iodine-based clinical agents, such as Omnipaque^TM (GE Healthcare, Princeton, NJ, USA) and Fenestra (MediLumine, Montreal, QC, Canada)

o Preclinical contrast agent eXIA 160XL (Binitio Biomedical, Inc., Ottawa, ON, Canada) and ExiTron^TM nano 12000 (Miltenyi Biotec GmbH, Germany)

Molecular imaging is a type of medical imaging that provides detailed pictures of what is happening inside the body at the molecular and cellular level. Where other diagnostic imaging procedures, such as x-rays, computed tomography (CT) and ultrasound, predominantly offer anatomical pictures, molecular imaging allows physicians to see how cell is functioning and to measure its chemical and biological processes.

PET and SPECT are imaging techniques in which a radionuclide is synthetically introduced into a molecule (a ligand, peptide, antibody, antibody fragments, etc.) of potential biological relevance/interest and administered to an animal or a patient. When the radiotracer is injected into the studied subject, the subsequent uptake of the radiotracer is measured over time and used to obtain information about the physiological, cellular and molecular process of interest.

Whereas PET and SPECT rely on similar principles to produce their images, important differences in instrumentation, radiochemistry, and experimental applications are dictated by inherent differences in their respective physics of photon emission. See schematic figures below for each principle.

Computer Tomography (CT) scan is based on X-ray principles. As X-rays pass through the body, they are absorbed at different levels, creating a matrix or profile of X-ray beams of different strengths. As the X-ray profile is registered on film, it creates an image. For a CT image, the film is replaced by a gently curved detector that measures the X-ray profile. The Figure shows the basic geometry of a CT scanner. This X-ray source is linked to the detector array in such a way that both are able to rotate together around the subject. A large number of detectors are used to enable an adequate number of images to be obtained across the entire scan circle. Unlike traditional X-ray examinations, CT employs tomography (imaging by sections) and thus results in a three-dimensional anatomic image of the subject being scanned.

CT Principle schematic

Single Photon Emission Computer Tomography (SPECT) is a nuclear medicine tomographic imaging technique using gamma-emitting tracers. Gamma-ray photons emitted from the internal distributed radiopharmaceutical penetrate through the animal’s body and are detected by a single or a set of collimated radiation detectors. Most of the detectors used in current SPECT systems are based on a single or multiple NaI(TI) scintillation detectors. SPECT imaging instrument acquires projection data from different views around the subject (animal or patient to provide three-dimensional (tomographic) images of the distribution of radioactive tracer molecules. The most common radiotracer for SPECT is Technetium-99m (^99mTc).

Positron Emission Tomography (PET) is a nuclear medicine functional imaging technique using Betta-emitting tracers. The radiotracer accumulates in the tissue to be studied, and its radionuclide decays by emission of a positron (anti-electron). After travelling at most a few millimeters, a positron will collide with an electron, simultaneously releasing two gamma rays (photons) with an energy of 511 keV into opposite directions. These two photons are detected by the PET camera and simultaneously localized within a fixed period of time by a series of opposing detectors, which correspond to multiple rings of scintillation crystals. By collecting a statistically significant number of radioactive events, mathematical algorithms reconstruct a 3D image that shows the distribution of the positron-emitting molecules in the whole body. The most common radiotracer for PET is ¹⁸F-FDG.

Scan-RAM Radio-TLC Scanner from LabLogic has been designed to analyse proteins labeled with PET and SPECT radiotracers.

Univentor 410 Anaesthesia Unit

Univentor Anaesthesia Unit

NanoDrop Spectrophotometer

Planning a Study on microPET

Contact QCPU scientist to discuss the feasibility of conducting your study, study protocols, tracers required for your study and their availability.
Submit a registration form for your study
Apply for Queen’s Ethics and Animal Care committee approval.
Complete the Queen’s Radiation Safety Course if you will be present during scanning (Please submit the course certificate).
Complete any relevant Animal Care courses if you will be involved in animal handling/care during scanning.
Plan for a pilot experiment before the first scan can be scheduled.

Notable Publications and Presentations

1. L. Tian, P. Y. Xiong, E. Alizadeh, P. A. D. Lima, F. Potus, A. Martin, S. L. Archer, Supra-coronary Aortic Banding Improves Right Ventricular Function in Experimental Pulmonary Arterial Hypertension by Increasing Systolic Right Coronary Artery Perfusion, Acta Physiologica. 229 (4) (2020), 1-17.

2. A. Dasgupta, D. Wu, L. Tian, P. Y. Xiong, K. J. Dunham-Snary, K. H. Chen, E. Alizadeh, M. Motamed, F. Potus, C. C. T. Hindmarch and S. L. Archer, Mitochondria in the Pulmonary Vasculature in Health and Disease: Oxygen-sensing, Metabolism, and Dynamics, Compr. Physiol. 10(2) (2020), 713-765.

3. E. Alizadeh, Pre-clinical Multi-modality Imaging: The Lost Ring in the Chain of Radiation Physics Research to Clinical Translation, Physics Colloquium, Carleton University, March 2021, Ottawa, ON, Canada.

4. Stephen Archer, COVID-19 pneumonia: SARS-CoV-2 attacks mitochondria in the cardiopulmonary system, NILabs' Scientific Event at the Society of Nuclear Medicine and Molecular Imaging (SNMMI), June 2021.

https://www.milabs.com/aiovg_videos/imaging-sars-cov-2-attacks-mitochondria-in-cardiopulmonary-cells-in-covid-19-pneumonia/

Small-Animal Imaging Laboratory (SAIL)