Hyperpolarized Xenon-129 Chemical Exchange Saturation Transfer (HyperCEST) Molecular Imaging: Achievements and Future Challenges.

Molecular magnetic resonance imaging (MRI) is an emerging field that is set to revolutionize our perspective of disease diagnosis, treatment efficacy monitoring, and precision medicine in full concordance with personalized medicine. A wide range of hyperpolarized (HP) Xe biosensors have been recently developed, demonstrating their potential applications in molecular settings, and achieving notable success within studies. The favorable nuclear magnetic resonance properties of Xe, coupled with its non-toxic nature, high solubility in biological tissues, and capacity to dissolve in blood and diffuse across membranes, highlight its superior role for applications in molecular MRI settings.

R3-Noria-methanesulfonate: A Molecular Cage with Superior Hyperpolarized Xenon-129 MRI Contrast.

Hyperpolarized (HP) xenon-129 (Xe) magnetic resonance imaging (MRI) has the potential to be used as a molecular imaging modality. For this purpose, numerous supramolecular cages have been developed and evaluated in the past. Herein, we report a novel and unique macrocycle that can be successfully utilized for xenon MRI, the resorcinarene trimer methanesulfonate (R3-Noria-MeSOH).

Cucurbit[6]uril Hyperpolarized Chemical Exchange Saturation Transfer Pulse Sequence Parameter Optimization and Detectability Limit Assessment at 3.0T.

The front cover artwork is provided by Prof. Mitchell S. Albert's group at Lakehead University.

Cucurbit[6]uril Hyperpolarized Chemical Exchange Saturation Transfer Pulse Sequence Parameter Optimization and Detectability Limit Assessment at 3.0T.

Molecular imaging is the future of personalized medicine; however, it requires effective contrast agents. Hyperpolarized chemical exchange saturation transfer (HyperCEST) can boost the signal of Hyperpolarized Xe MRI and render it a molecular imaging modality of high efficiency. Cucurbit[6]uril (CB6) has been successfully employed in vivo as a contrast agent for HyperCEST MRI, however its performance in a clinical MRI scanner has yet to be optimized.

Revealing a Third Dissolved-Phase Xenon-129 Resonance in Blood Caused by Hemoglobin Glycation.

Hyperpolarized (HP) xenon-129 (Xe), when dissolved in blood, has two NMR resonances: one in red blood cells (RBC) and one in plasma. The impact of numerous blood components on these resonances, however, has not yet been investigated. This study evaluates the effects of elevated glucose levels on the chemical shift (CS) and T2* relaxation times of HP Xe dissolved in sterile citrated sheep blood for the first time.

Hybrid silicon-tellurium-dioxide DBR resonators coated in PMMA for biological sensing.

We report on silicon waveguide distributed Bragg reflector (DBR) cavities hybridized with a tellurium dioxide (TeO) cladding and coated in plasma functionalized poly (methyl methacrylate) (PMMA) for label free biological sensors. We describe the device structure and fabrication steps, including reactive sputtering of TeO and spin coating and plasma functionalization of PMMA on foundry processed Si chips, as well as the characterization of two DBR designs via thermal, water, and bovine serum albumin (BSA) protein sensing. Plasma treatment on the PMMA films was shown to decrease the water droplet contact angle from ∼70 to ∼35°, increasing hydrophilicity for liquid sensing, while adding functional groups on the surface of the sensors intended to assist with immobilization of BSA molecules.

Postacute COVID-19 Syndrome: Xe MRI Ventilation Defects and Respiratory Outcomes 1 Year Later.

Background In individuals with postacute COVID-19 syndrome (PACS) and normal pulmonary function, xenon 129 (Xe) MRI ventilation defects, abnormal quality-of-life scores, and exercise limitation were reported 3 months after infection; the longitudinal trajectory remains unclear. Purpose To measure and compare pulmonary function, exercise capacity, quality of life, and Xe MRI ventilation defect percent (VDP) in individuals with PACS evaluated 3 and 15 months after COVID-19 infection. Materials and Methods In this prospective study, participants with PACS aged 18-80 years were enrolled between July 2020 and August 2021 from two quaternary care centers.

Longitudinal follow-up of postacute COVID-19 syndrome: DL, quality-of-life and MRI pulmonary gas-exchange abnormalities.

Xe MRI red blood cell to alveolar tissue plasma ratio (RBC:TP) abnormalities have been observed in ever-hospitalised and never-hospitalised people with postacute COVID-19 syndrome (PACS). But, it is not known if such abnormalities resolve when symptoms and quality-of-life scores improve. We evaluated 21 participants with PACS, 7±4 months (baseline) and 14±4 months (follow-up) postinfection.

Persistent Xe MRI Pulmonary and CT Vascular Abnormalities in Symptomatic Individuals with Post-acute COVID-19 Syndrome.

Background: In patients with post-acute COVID-19 syndrome (PACS), abnormal gas-transfer and pulmonary vascular density have been reported, but such findings have not been related to each other or to symptoms and exercise limitation. The pathophysiologic drivers of PACS in patients previously infected with COVID-19 who were admitted to in-patient treatment in hospital (or ever-hospitalized patients) and never-hospitalized patients are not well understood.

Purpose: To determine the relationship of persistent symptoms and exercise limitation with xenon 129 (Xe) MRI and CT pulmonary vascular measurements in individuals with PACS.

Xe MRI ventilation defects in ever-hospitalised and never-hospitalised people with post-acute COVID-19 syndrome.

Background: Patients often report persistent symptoms beyond the acute infectious phase of COVID-19. Hyperpolarised Xe MRI provides a way to directly measure airway functional abnormalities; the clinical relevance of Xe MRI ventilation defects in ever-hospitalised and never-hospitalised patients who had COVID-19 has not been ascertained. It remains unclear if persistent symptoms beyond the infectious phase are related to small airways disease and ventilation heterogeneity.

Hyperpolarized Xe imaging of the brain: Achievements and future challenges.

Hyperpolarized (HP) xenon-129 ( Xe) brain MRI is a promising imaging modality currently under extensive development. HP Xe is nontoxic, capable of dissolving in pulmonary blood, and is extremely sensitive to the local environment. After dissolution in the pulmonary blood, HP Xe travels with the blood flow to the brain and can be used for functional imaging such as perfusion imaging, hemodynamic response detection, and blood-brain barrier permeability assessment.

Hyperpolarized Xe multi-slice imaging of the human brain using a 3D gradient echo pulse sequence.

Purpose: To demonstrate the possibility of performing multi-slice in-vivo human brain MRI using hyperpolarized (HP) xenon-129 ( Xe) in two different orientations and to calculate the signal-to-noise ratio (SNR).

Methods: Two healthy female participants were imaged during a single breath-hold of HP Xe using a Philips Achieva 3.0T MRI scanner (Philips, Andover, MA).

The effects of an initial depolarization pulse on dissolved phase hyperpolarized Xe brain MRI.

Purpose: To evaluate the effect of an initial 90° depolarization RF pulse on the dissolved-phase hyperpolarized (HP) xenon-129 ( Xe) brain imaging and to compare the SNR variability of HP Xe images acquired without an initial depolarization RF pulse to those following the initial depolarization pulse.

Methods: Five cognitive normal healthy volunteers were imaged using a Philips Achieva 3.0T MRI scanner during a single breath-hold following inhalation of 1 L of HP Xe.

Cyclodextrin-Based Contrast Agents for Medical Imaging.

Cyclodextrins (CDs) are naturally occurring cyclic oligosaccharides consisting of multiple glucose subunits. CDs are widely used in host-guest chemistry and biochemistry due to their structural advantages, biocompatibility, and ability to form inclusion complexes. Recently, CDs have become of high interest in the field of medical imaging as a potential scaffold for the development of a large variety of the contrast agents suitable for magnetic resonance imaging, ultrasound imaging, photoacoustic imaging, positron emission tomography, single photon emission computed tomography, and computed tomography.

Decacationic Pillar[5]arene: A New Scaffold for the Development of Xe MRI Imaging Agents.

A decacationic water-soluble pillar[5]arene possessing a nonsolvated hydrophobic core has been designed and synthesized. This supramolecular host is capable of binding xenon, as evidenced by hyperCEST depletion experiments. Fluorescence-based studies also demonstrate that xenon binds into the cavity of the pillararene with an association constant of 4.

Hyperpolarized Xe Time-of-Flight MR Imaging of Perfusion and Brain Function.

Perfusion measurements can provide vital information about the homeostasis of an organ and can therefore be used as biomarkers to diagnose a variety of cardiovascular, renal, and neurological diseases. Currently, the most common techniques to measure perfusion are O positron emission tomography (PET), xenon-enhanced computed tomography (CT), single photon emission computed tomography (SPECT), dynamic contrast enhanced (DCE) MRI, and arterial spin labeling (ASL) MRI. Here, we show how regional perfusion can be quantitively measured with magnetic resonance imaging (MRI) using time-resolved depolarization of hyperpolarized (HP) xenon-129 (Xe), and the application of this approach to detect changes in cerebral blood flow (CBF) due to a hemodynamic response in response to brain stimuli.

Evaluation of fluorine-19 magnetic resonance imaging of the lungs using octafluorocyclobutane in a rat model.

Purpose: To test octafluorocyclobutane (OFCB) as an inhalation contrast agent for fluorine-19 MRI of the lung, and to compare the image quality of OFCB scans with perfluoropropane (PFP) scans THEORY AND METHODS: After normalizing for the number of signal averages, a theoretical comparison between the OFCB signal-to-noise ratio (SNR) and PFP SNR predicted the average SNR advantage of 90% using OFCB during gradient echo imaging. The OFCB relaxometry was conducted using single-voxel spectroscopy and spin-echo imaging. A comparison of OFCB and PFP SNRs was performed in vitro and in vivo.

Molecular Imaging of Fluorinated Probes for Tau Protein and Amyloid-β Detection.

Alzheimer's disease (AD) is the most common form of dementia and results in progressive neurodegeneration. The incidence rate of AD is increasing, creating a major public health issue. AD is characterized by neurofibrillary tangles (NFTs) composed of hyperphosphorylated tau protein and senile plaques composed of amyloid-β (Aβ).

In-Vivo Retention of 5-Fluorouracil Using F Magnetic Resonance Chemical Shift Imaging in Colorectal Cancer in a Murine Model.

Colorectal cancer is the third leading cause of cancer death worldwide. 5-Fluorouracil (5-FU) is one of the most commonly used chemotherapies for treatment of solid tumours, including colorectal cancer. The efficacy of treatment is dependent on tumour type and can only be determined six weeks after beginning chemotherapy, with only 40-50% of patients responding positively to the 5-FU therapy.

F MRI of the Lungs Using Inert Fluorinated Gases: Challenges and New Developments.

Fluorine-19 ( F) MRI using inhaled inert fluorinated gases is an emerging technique that can provide functional images of the lungs. Inert fluorinated gases are nontoxic, abundant, relatively inexpensive, and the technique can be performed on any MRI scanner with broadband multinuclear imaging capabilities. Pulmonary F MRI has been performed in animals, healthy human volunteers, and in patients with lung disease.

Adsorption of Maleic Acid Monomer on the Surface of Hydroxyapatite and TiO: A Pathway toward Biomaterial Composites.

Poly(styrene- alt-maleic acid) adsorption on hydroxyapatite and TiO (rutile) was studied using experimental techniques and complemented by ab initio simulations of adsorption of a maleic acid segment as a subunit of the copolymer. Ab initio calculations suggest that the maleic acid segment forms a strong covalent bonding to the TiO and hydroxyapatite surfaces. If compared to vacuum, the presence of a solvent significantly reduces the adsorption strength as the polarity of the solvent increases.

Inhaled Xenon Washout as a Biomarker of Alzheimer's Disease.

Biomarkers have the potential to aid in the study of Alzheimer’s disease (AD); unfortunately, AD biomarker values often have a high degree of overlap between healthy and AD individuals. This study investigates the potential utility of a series of novel AD biomarkers, the sixty second Xe retention time, and the xenon washout parameter, based on the washout of hyperpolarized Xe from the brain of AD participants following inhalation. The xenon washout parameter is influenced by cerebral perfusion, T1 relaxation of xenon, and the xenon partition coefficient, all factors influenced by AD.

Brain Imaging Using Hyperpolarized Xe Magnetic Resonance Imaging.

Hyperpolarized (HP) Xe magnetic resonance imaging (MRI) is a novel iteration of traditional MRI that relies on detecting the spins of H. Since Xe is a gaseous signal source, it can be used for lung imaging. Additionally, Xe dissolves in the blood stream and can therefore be detectable in the brain parenchyma and vasculature.

Cyclodextrin-Based Pseudorotaxanes: Easily Conjugatable Scaffolds for Synthesizing Hyperpolarized Xenon-129 Magnetic Resonance Imaging Agents.

Hyperpolarized (HP) xenon-129 (Xe) magnetic resonance (MR) imaging has the potential to detect biological analytes with high sensitivity and high resolution when coupled with xenon-encapsulating molecular probes. Despite the development of numerous HP Xe probes, one of the challenges that has hampered the translation of these agents from in vitro demonstration to in vivo testing is the difficulty in synthesizing the Xe-encapsulating cage molecule. In this study, we demonstrate that a pseudorotaxane, based on a γ-cyclodextrin macrocycle, is easily synthesized in one step and is detectable using HyperCEST-enhanced Xe MR spectroscopy.