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 15O 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 (129Xe), and the application of this approach to detect changes in cerebral blood flow (CBF) due to a hemodynamic response in response to brain stimuli. The investigated HP 129Xe Time-of-Flight (TOF) technique produced perfusion images with an average signal-to-noise ratio (SNR) of 10.35. Furthermore, to our knowledge, the first hemodynamic response (HDR) map was acquired in healthy volunteers using the HP 129Xe TOF imaging. Responses to visual and motor stimuli were observed. The acquired HP TOF HDR maps correlated well with traditional proton blood oxygenation level-dependent functional MRI. Overall, this study expands the field of HP MRI with a novel dynamic imaging technique suitable for rapid and quantitative perfusion imaging.
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 pathophysiological drivers of PACS in ever- and never-hospitalized patients are not well-understood. Purpose To determine the relationship of persistent symptoms and exercise limitation with 129 Xe MRI and CT pulmonary vascular measurements in individuals with PACS. Materials and Methods In this prospective study, patients with PACS aged 18-80 years with a positive PCR COVID test were recruited from a quaternary-care COVID-19 clinic between April and October 2021. Participants with PACS underwent spirometry, diffusing-capacity-of-the-lung- for-carbon-monoxide (DL co ), 129 Xe MRI, and chest CT. Healthy controls had no prior history of COVID-19 underwent spirometry, DL co , and 129 Xe MRI. The 129 Xe MRI red-blood-cell (RBC) to alveolar-barrier signal ratio, RBC area-under-the-curve (AUC), CT volume-of-pulmonary-vessels with cross-sectional-area <5mm 2 (BV5), and total-blood-volume (TBV) were quantified. St. George's Respiratory Questionnaire (SGRQ), International Physical Activity Questionnaire (IPAQ) and modified Borg Dyspnea Scale (mBDS) measured quality-of-life, exercise limitation and dyspnea. Differences between groups were compared using Welch's T-tests or Welch's ANOVA. Relationships were evaluated using Pearson (r) and Spearman (ρ) correlations. Results Forty participants were evaluated including six controls (mean age, 35±15 years[standard deviation], 3 women) and 34 participants with PACS (mean age, 53±13 years[SD], 18 women), of which 22 were never-hospitalized. The 129 Xe MRI RBC:barrier ratio was lower in ever- hospitalized participants (P=.04) compared to controls. BV5 correlated with RBC AUC (ρ=.44,P=.03). The 129 Xe MRI RBC:barrier ratio was related to DL co (r=.57,P=.002) and FEV 1 (ρ=.35,P=.03); RBC AUC was related to dyspnea (ρ=-.35,P=.04) and IPAQ score (ρ=.45,P=.02). Conclusion 129 Xe MRI measurements were lower in ever- hospitalized participants with post- acute COVID-19-syndrome, 34±25 weeks post-infection compared to controls. 129 Xe MRI measures were associated with CT pulmonary vascular density, DL co , exercise capacity, and dyspnea. ClinicalTrials.gov : NCT04584671 See also the editorial by Wild and Collier .
Hyperpolarized (HP) xenon-129 ( 129 Xe) MRI has proved to be a valuable tool for imaging lung ventilation 1-7 and evaluating pulmonary gas transfer. [8][9][10][11][12] After inhalation, HP 129 Xe freely dissolves in pulmonary blood 12,13 and is transferred to highly perfused organs. Because HP 129 Xe has a sufficiently long T 1 relaxation time in the blood, it is possible to use HP 129 Xe as an inhalation contrast agent for dissolvedphase imaging. [14][15][16][17] Therefore, it has been recently used for
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 129 Xe MR spectroscopy.
To demonstrate the possibility of performing multi-slice in-vivo human brain MRI using hyperpolarized (HP) xenon-129 ( 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 129 Xe using a Philips Achieva 3.0T MRI scanner (Philips, Andover, MA).Each HP 129 Xe multi-slice brain image was acquired during separate HP 129 Xe breath-holds using 3D gradient echo (GRE) imaging. The acquisition started 10 s after the inhalation of 1 L of HP 129 Xe. Overall, four sagittal and three axial images were acquired (seven imaging sessions per participant). The SNR was calculated for each slice in both orientations. Results: The first ever HP 129 Xe multi-slice images of the brain were acquired in axial and sagittal orientations. The HP 129 Xe signal distribution correlated well with the gray matter distribution. The highest SNR values were close in the axial and sagittal orientations (19.46 ± 3.25 and 18.76 ± 4.94, respectively). Additionally, anatomical features, such as the ventricles, were observed in both orientations. Conclusion:The possibility of using multi-slice HP 129 Xe human brain magnetic resonance imaging was demonstrated for the first time. HP 129 Xe multi-slice MRI can be implemented for brain imaging to improve current diagnostic methods.
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 4.6 × 10 3 M −1 . These data indicate that the water-soluble pillararene is a potential scaffold for building contrast agents that can be detected by xenon-129 magnetic resonance imaging.
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). Currently, a definitive diagnosis of AD is accomplished post-mortem. Thus, the use of molecular probes that are able to selectively bind to NFTs or Aβ can be valuable tools for the accurate and early diagnosis of AD. The aim of this review is to summarize and highlight fluorinated molecular probes that can be used for molecular imaging to detect either NFTs or Aβ. Specifically, fluorinated molecular probes used in conjunction with 19F MRI, PET, and fluorescence imaging will be explored.
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. Five healthy Sprague‐Dawley rats were imaged during single breath‐hold and continuous breathing using a Philips Achieva 3.0T MRI scanner (Philips, Andover, MA). The scan time was constant for both gases. Statistical comparison between PFP and OFCB scans was conducted using a paired t test and by calculating the Bayes factor. Results Spin‐lattice (T1) and effective spin‐spin (T2∗) relaxation time constants of the pure OFCB gas were determined as 28.5 ± 1.2 ms and 10.5 ± 1.8 ms, respectively. Mixing with 21% of oxygen decreased T1 by 30% and T2∗ by 20%. The OFCB in vivo images showed 73% higher normalized SNR on average compared with images acquired using PFP. The statistical significance was shown by both paired t test and calculated Bayes factors. The experimental results agree with theoretical calculations within the error of the relaxation parameter measurements. Conclusion The quality of the lung images acquired using OFCB was significantly better compared with PFP scans. The OFCB images had higher a SNR and were artifact‐free.
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