Simultaneous in vivo positron emission tomography and magnetic resonance imaging

Positron emission tomography (PET) and magnetic resonance imaging (MRI) are widely used in vivo imaging technologies with both clinical and biomedical research applications. The strengths of MRI include high-resolution, high-contrast morphologic imaging of soft tissues; the ability to image physiologic parameters such as diffusion and changes in oxygenation level resulting from neuronal stimulation; and the measurement of metabolites using chemical shift imaging. PET images the distribution of biologically targeted radiotracers with high sensitivity, but images generally lack anatomic context and are of lower spatial resolution. Integration of these technologies permits the acquisition of temporally correlated data showing the distribution of PET radiotracers and MRI contrast agents or MR-detectable metabolites, with registration to the underlying anatomy. An MRI-compatible PET scanner has been built for biomedical research applications that allows data from both modalities to be acquired simultaneously. Experiments demonstrate no effect of the MRI system on the spatial resolution of the PET system and <10% reduction in the fraction of radioactive decay events detected by the PET scanner inside the MRI. The signal-to-noise ratio and uniformity of the MR images, with the exception of one particular pulse sequence, were little affected by the presence of the PET scanner. In vivo simultaneous PET and MRI studies were performed in mice. Proof-of-principle in vivo MR spectroscopy and functional MRI experiments were also demonstrated with the combined scanner

EANM/SNMMI Guideline for 18F-FDG Use in Inflammation and Infection

The Society of Nuclear Medicine and Molecular Imaging (SNMMI) is an international scientific and professional organization founded in 1954 to promote the science, technology and practical application of nuclear medicine. Its 16,000 members are physicians, technologists, and scientists specializing in the research and practice of nuclear medicine. In addition to publishing journals, newsletters, and books, the SNMMI also sponsors international meetings and workshops designed to increase the competencies of nuclear medicine practitioners and to promote new advances in the science of nuclear medicine. The European Association of Nuclear Medicine (EANM) is a professional nonprofit medical association that facilitates communication worldwide between individuals pursuing clinical and research excellence in nuclear medicine. The EANM was founded in 1985

What do we know about dynamic glucose-enhanced (DGE) MRI and how close is it to the clinics? Horizon 2020 GLINT consortium report

Cancer is one of the most devastating diseases that the world is currently facing, accounting for 10 million deaths in 2020 (WHO). In the last two decades, advanced medical imaging has played an ever more important role in the early detection of the disease, as it increases the chances of survival and the potential for full recovery. To date, dynamic glucose-enhanced (DGE) MRI using glucose-based chemical exchange saturation transfer (glucoCEST) has demonstrated the sensitivity to detect both D-glucose and glucose analogs, such as 3-oxy-methyl-D-glucose (3OMG) uptake in tumors. As one of the recent international efforts aiming at pushing the boundaries of translation of the DGE MRI technique into clinical practice, a multidisciplinary team of eight partners came together to form the "glucoCEST Imaging of Neoplastic Tumors (GLINT)" consortium, funded by the Horizon 2020 European Commission. This paper summarizes the progress made to date both by these groups and others in increasing our knowledge of the underlying mechanisms related to this technique as well as translating it into clinical practice

Description and Practical Application of the Physiologic Distribution of 3’-Deoxy-3’-[18F]Fluorothymidine in Companion Animals

Access to positron emission tomography (PET), and more recently PET combined with computed tomography (PET/CT), is increasing in veterinary medicine. This molecular imaging technology allows clinicians to map biological functions within patients based on the distribution and selective uptake of specialized positron-emitting radiopharmaceuticals. Although most clinical studies utilize 2-deoxy-2-[18F]fluoro-Dglucose (18FDG), a versatile but relatively nonspecific tracer that interrogates the energy metabolism of tissues, there is a growing need to establish reference values for alternative or adjunct tracers in veterinary species. Among these is 3’-deoxy-3’- [18F]fluorothymidine (18FLT), a thymidine analog that selectively accumulates in proliferating tissues. In the present work, 18FLT distribution in clinically healthy adult dogs and young adult cats was imaged using a state-of-the-art PET/CT scanner to define normal uptake levels within numerous tissues, including major parenchymal organs, bone marrow, and other sites of increased radiopharmaceutical uptake. The marrow signal was subsequently segmented into separate skeletal regions, and used to quantitatively define the adult marrow distribution pattern in the dog. Marrow activity is concentrated in the vertebral column (particularly within the thoracic and lumbar regions), sternum, ribs, and proximal aspects of the appendicular skeleton in the adult dog. Feline marrow distribution is similar; however, considerable uptake within more distal appendicular structures suggests that age-related marrow conversion is ongoing in 3-year-old cats. Outside the marrow compartment, physiologic uptake was observed within the urinary and biliary systems, intestinal tract, and variably within lymphoid structures. Prominent uptake within the hepatic parenchyma was also observed in cats, but not dogs, at the times imaged in this study. The details of normal canine and feline 18FLT biodistribution included in this dissertation may be used to inform lesion interpretation in dogs and cats with suspected disease. Likewise, quantitative details of adult marrow distribution in dogs may be used by clinicians to guide the selection of marrow sampling sites or inform tissue-sparing efforts during radiotherapeutic planning in canine patients

Understanding the Structural and Functional Correlates of Acute Lung Inflammation in Two Murine Models

The outcome of lung inflammation is important to host survival as lungs are necessary for oxygen exchange and fighting pathogens or any injurious stimuli. Thus, diagnosing and understanding the kinetics of lung inflammation is an emerging technological area in the field of imaging research and development. Dr. Aulakh’s lab has two separate established models of neutrophilic murine acute lung injury namely, acute low-dose (0.05 ppm) ozone-induced and intranasal bacterial lipopolysaccharide (LPS)-induced lung inflammation. In order to characterize the dynamics of these models, there are two research hypotheses of my project, which are a) acute low-dose ozone exposure causes lung [18F]F-FDG retention because of increased leukocyte glucose uptake due to inflammation as assessed by sequential micro-Positron Emission Tomography-Computed tomography (microPET-CT) in murine lungs, similar to the effects of intranasal bacterial lipopolysaccharide, LPS and b) acute low-dose ozone exposure induces an increase in ultra-small-angle scatter (USAXS) (due to alveolar recruitment), absorption (due to alveolar edema) and a decrease in refraction (due to peri-bronchiolar edema) comparable to intranasal LPS induced changes in these X-ray optical properties as assessed by Lung Multiple Image X-Radiography (MIR). Thus, the premise of my thesis is to test the utility of longitudinal non-invasive imaging modalities, namely sequential [18F]-fluoro-deoxy glucose ([18F]F-FDG) positron emission tomography-computed tomography (PET-CT) and synchrotron multiple image X-radiography (MIR), to assess the progression of acute murine low-dose ozone or intranasal bacterial lipopolysaccharide (LPS) induced lung inflammation over 24 and 70 h time periods, respectively. Both ozone and LPS induced an increase in murine lung [18F]F-FDG standard uptake ratio (SUR) and a heterogenous lung distribution which was unlike the craniocaudal [18F]F-FDG gradient observed in lungs before any exposure (called as baseline or control [18F]F-FDG). The whole-body distribution profiles revealed that lung [18F]F-FDG activity was higher and prolonged up to 28 h in LPS compared to ozone exposed mice. While [18F]F-FDG is a useful marker to highlight areas with high metabolic uptake of glucose in cells such as neutrophils and macrophages recruited during inflammation, the resolution of PET-CT (hundreds of μm) precludes the evaluation of microscopic histopathologic changes especially in the alveoli. Using lung hematoxylin and eosin stained cryosections, the ratios of total lung tissue to air spaces and specifically alveolar parenchyma to air spaces were assessed in mice lungs exposed to 0.05 ppm ozone for 2 h. Results from the X-ray CT lung tissue volume quantifications as well as the histologically derived percent-stained lung or alveolar area quantifications suggest significant damage that is observed as reduced percentage area as well as variability or standard deviation (S.D.) of binary lung images in mice immediately i.e., at 0 h and 6 h after exposure to 2 h of 0.05 ppm ozone. Alveolar damage was also significant at 0 h as shown by reduction in percentage area and S.D. in the binary image region restricted to alveoli. The synchrotron study aimed at following mice lungs before, immediately i.e., at 0 h, and thereafter at 24, 48 or 70 h after saline, bacterial lipopolysaccharide (LPS, 50 μg), or low dose (0.05 ppm for 2 h) ozone exposure. Our results indicate that the lung ultra-small-angle scatter (USAXS), which is a metric of air-tissue boundaries and refraction (which is due to bending of X-rays across air-tissue conducting airways) reduces, especially in the cranial part of left lung, with a corresponding increase in absorption upon exposure to LPS or ozone and is detectable up to 70 h. The changes in lung X-ray optical properties are indicative of the gross inflammatory changes, in response to LPS or ozone exposure, as indicated by increases in lung absorption but reduction in refraction and USAXS. Overall, the results from my project indicate that for a comprehensive analysis of lung inflammation, a combination of lung histological analysis along with objective lung image analysis as described in the longitudinal microPET-CT and lung MIR experiments form powerful techniques for sensitive delineation of inflammatory changes in gross lung structure and function

Approaches for the optimization of MR protocols in clinical hybrid PET/MRI studies

Magnetic resonance imaging (MRI) is the examination method of choice for the diagnosis of a variety of diseases. MRI allows us to obtain not only anatomical information but also identification of physiological and functional parameters such as networks in the brain and tumor cellularity, which plays an increasing role in oncologic imaging, as well as blood flow and tissue perfusion. However, in many cases such as in epilepsy, degenerative neurological diseases and oncological processes, additional metabolic and molecular information obtained by PET can provide essential complementary information for better diagnosis. The combined information obtained from MRI and PET acquired in a single imaging session allows a more accurate localization of pathological findings and better assessment of the underlying physiopathology, thus providing a more powerful diagnostic tool. Two hundred and twenty-one patients were scanned from April 2011 to January 2012 on a Philips Ingenuity TF PET/MRI system. The purpose of this review article is to provide an overview of the techniques used for the optimization of different protocols performed in our hospital by specialists in the following fields: neuroradiology, head and neck, breast, and prostate imaging. This paper also discusses the different problems encountered, such as the length of studies, motion artifacts, and accuracy of image fusion including physical and technical aspects, and the proposed solution