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• Magnetic resonance imaging and spectroscopy
• Optical imaging
• Photoacoustic imaging
• CT imaging
• SPECT imaging
• Molecular imaging
• PET/CT imaging

Magnetic resonance imaging and spectroscopy

Magnetic resonance imaging is a high-resolution imaging modality capable of superior soft-tissue contrast. Magnetic resonance spectroscopy may be employed for assessment of tissue and organ function. 

The Bioimaging and Applied Research Core maintains a 7 Tesla Bruker Biospec preclinical MRI scanner, capable of rodent and small mammal imaging with a broad range of image and spectroscopic acquisition paradigms. Imaging and spectroscopic protocols including: T1- and T2-weighted imaging, diffusion weighted and diffusion tensor imaging, echo-planar imaging, ultra-short TE imaging, cardiac CINE imaging, and Point-resolved and Stimulated echo spectroscopic acquisition methods for proton and various X-nuclei.

Full physiological monitoring, including respiratory/cardiac gating and thermoregulation capabilities are available. In addition to proton imaging and spectroscopy, RF coils are available for fluorine, phosphorus and carbon acquisitions.  MRI technical expertise is provided to assist researchers with optimization of imaging paradigms, data acquisition and analysis.

Optical imaging

Optical imaging uses light to interrogate cellular and molecular function in the living body, as well as in plant and in vitro samples. Images are generated by using photons of light in the wavelength range from ultraviolet to near infrared.  Contrast is derived through the use of:

• exogenous agents (i.e., dyes or probes) that provide a signal
• endogenous molecules with optical signatures (i.e., NADH, hemoglobin, collagens, etc.)
• reporter genes

Fluorescence protein imaging uses endogenous or exogenous molecules or materials that emit light when activated by an external light source such as a laser. An external light of an appropriate wavelength is used to excite a target molecule, which then fluoresces by releasing longer-wavelength, lower-energy light. Fluorescence imaging provides the ability to localize and measure gene expression including normally expressed and aberrant genes, proteins and other pathophysiologic processes. Other potential uses include cell trafficking, tagging superficial structures, detecting lesions, and monitoring tumor growth and response to therapy. The Bioimaging and Applied Research Core maintains a CRi Maestro2 multispectral fluorescence imaging system capable of in vitro and in vivo small mammal imaging with multispectral analysis.

Photoacoustic imaging

Photoacoustic imaging (PAI) is a hybrid imaging system that merges optical illumination with ultrasound detection to achieve high resolution optical contrast images to a few centimeters in depth. 

PAI capitalizes on the intrinsic optical absorption of chromophores in tissue such as hemoglobin, melanin, lipid and water. As each of these chromophores exhibits its own characteristic absorption spectra, PAI at multiple wavelengths allows for their relative quantification and helps to investigate physiological changes in disorders to understand the mechanism behind them and how they can be managed effectively.

The Bioimaging and Applied Research Core maintains an iTheraMedical MSOT inVision optoacoustic imaging platform for preclinical research.

CT imaging

CT scanner uses a motorized X-ray source that rotates around a circular opening called a gantry. During a CT scan, the subject is positioned on a bed within the gantry by defining a field of view (FOV). The X-ray tube rotates around the gantry, shooting narrow beams of X-rays through the body the subject. Instead of film, CT scanners use special digital X-ray detectors located directly opposite the X-ray source. As the X-rays pass through the subject, they are picked up by the detectors and transmitted to a computer. Each time the X-ray source completes one full rotation, the CT computer uses sophisticated mathematical techniques to construct a 2D image slice of the patient. The thickness of the tissue represented in each image slice can vary depending on the CT machine used, but usually ranges from 1-10 millimeters. When a full slice is completed, the image is stored and the motorized bed is moved forward incrementally into the gantry. The X-ray scanning process is then repeated to produce another image slice. This process continues until the desired number of slices is collected. Image slices can either be displayed individually or stacked together by the computer to generate a 3D image of the subject showing the skeleton, organs and tissues with contrast based on their densities. These are quantified and expressed as Hounsfield units (HU) such as -1000 HU for air and 0 HU for water. This method has many advantages including the ability to rotate the 3D image in space or to view slices in succession, making it easier to find and study the exact regions of interest. Bones exhibit the highest density (+1000 HU) while lung parenchyma, body fat have densities relatively lower than water in terms of HU normalization. CT scanners: MultiScan LFER large bore research PET/CT and Inveon PET/SPECT/CT system.

SPECT imaging

Single photon emission computed tomography (SPECT) cameras acquire multiple planar views of the administered radioactivity in a subject positioned in the field of view. The data are then processed using suitable reconstruction algorithms to create cross sectional and 3D views of the subject. SPECT utilizes the single photons emitted by gamma-emitting radionuclides such as ^99mTc, ¹²³I, etc. Special collimators are used to image experimental subjects such as a mouse or a rat. SPECT is a useful imaging method to study nuclear molecular imaging and gene therapy using the sodium iodide symporter (NIS). In SPECT, image quality is compromised by several factors including photon attenuation, photon scatter, the partial volume effect, and motion artifacts. These variables also confound the capacity of SPECT to quantify the concentration of radioactivity within given volumes of interest in absolute units, e.g. as kilobecquerels per cubic centimeter. 

Often SPECT and PET are used in conjunction with CT imaging. This enables the investigator to have a sense of the anatomical information overlaid with the molecular/biochemical information. CT images are also useful for attenuation correction that could be used to improve image quality and accuracy. All these imaging methods could be combined with respiratory/cardiac gating to minimize data compromise due to motion of the organs of interest.

Inveon PET/SPECT/CT system

Molecular imaging

Molecular imaging is a multidisciplinary science that provides non-invasive visual characterization and measurement of the internal cellular functions and molecular processes of humans and other living organisms in their intact physiological environment. Amongst radionuclide based molecular imaging both PET and SPECT imaging methods could be used for such applications. [¹⁸F]Fluoro-2-deoxy-2-d-glucose  (FDG) is the most widely known molecular imaging tracer which is used as a surrogate marker of glucose metabolism in tumors and other tissues.

PET/CT imaging

Positron emission tomography (PET) cameras are capable of detecting paired 511-keV photons generated from the annihilation event of a positron and electron. The paired photons travel in opposite directions (180⁰ apart) along a line. These are detected by pairs of detectors kept on opposite sides in a ring configuration within the PET camera. This is called annihilation coincidence detection. Following the acquisition of the images of the positron emissions, the data are reconstructed in a manner similar to that used for SPECT. However, PET has a number of advantages compared to SPECT. Most importantly, PET has greater sensitivity and resolution combined with better quantitative abilities. See below for a number of vendor supplied PET tracers that could become available for molecular imaging at BARC.

PET tracers available for molecular imaging from vendors provided through BARC

• [¹⁸F]-FDG - [¹⁸F]Fluoro-2-deoxy-2-d-glucose
  [18F]FDG is useful to assess alterations in glucose metabolism in brain, cancer, cardiovascular diseases, Alzheimer’s disease and other central nervous system disorders, and infectious, autoimmune, and inflammatory diseases
• [¹⁸F]-FLT - 3'-deoxy-3'-[18F]fluorothymidine
  The uptake and accumulation of FLT are used as an index of cellular proliferation. [18F]FLT PET has been used to detect and monitor tumor proliferation, to evaluate the stages of tumor, and to detect metastases
• [¹⁸F]-NaF - sodium fluoride
  (¹⁸F-NaF) PET/CT provides high sensitivity and specificity for the assessment of bone and joint diseases. It is able to accurately differentiate malignant from benign bone lesions, especially when using dynamic quantitative approaches. There is also evidence on atherosclerosis imaging with 18F-sodium-fluoride (NaF) positron emission tomography (PET)

Efforts are underway to provide access to additional molecular imaging PET tracers to be obtained through vendors. BARC staff will help the core facility users in selecting the appropriate tracer and scanning methodology for their research applications.

• [F18] Fluciclovine (¹⁸F-Axumin - to identify suspected sites of prostate cancer recurrence in male)
• [F-18] Fluoroestradiol (a molecular marker for PET imaging in metastatic breast cancer)
• [F-18] Florbetaben (FBB) For Alzheimer’s disease, β-Amyloid, PET imaging
• [¹⁸F]-FAraG (PET imaging to non-invasively assess tumor infiltrating T-cells and assessment of immunomodulation)
• [¹⁸F]-FMISO (Evaluation of hypoxia and Tx resistance)
• [¹⁸F]-FHBG (PET reporter gene imaging)
• [⁸⁹Zr]-CD8 Immuno-PET imaging agent non-invasively tracks and quantifies tumor infiltrating CD8 T cells