Dataset Information

In vivo MR imaging of pulmonary perfusion and gas exchange in rats via continuous extracorporeal infusion of hyperpolarized 129Xe.

ABSTRACT:

Background

Hyperpolarized (HP) (129)Xe magnetic resonance imaging (MRI) permits high resolution, regional visualization of pulmonary ventilation. Additionally, its reasonably high solubility (>10%) and large chemical shift range (>200 ppm) in tissues allow HP (129)Xe to serve as a regional probe of pulmonary perfusion and gas transport, when introduced directly into the vasculature. In earlier work, vascular delivery was accomplished in rats by first dissolving HP (129)Xe in a biologically compatible carrier solution, injecting the solution into the vasculature, and then detecting HP (129)Xe as it emerged into the alveolar airspaces. Although easily implemented, this approach was constrained by the tolerable injection volume and the duration of the HP (129)Xe signal.

Methods and principal findings

Here, we overcome the volume and temporal constraints imposed by injection, by using hydrophobic, microporous, gas-exchange membranes to directly and continuously infuse (129)Xe into the arterial blood of live rats with an extracorporeal (EC) circuit. The resulting gas-phase (129)Xe signal is sufficient to generate diffusive gas exchange- and pulmonary perfusion-dependent, 3D MR images with a nominal resolution of 2×2×2 mm(3). We also show that the (129)Xe signal dynamics during EC infusion are well described by an analytical model that incorporates both mass transport into the blood and longitudinal relaxation.

Conclusions

Extracorporeal infusion of HP (129)Xe enables rapid, 3D MR imaging of rat lungs and, when combined with ventilation imaging, will permit spatially resolved studies of the ventilation-perfusion ratio in small animals. Moreover, EC infusion should allow (129)Xe to be delivered elsewhere in the body and make possible functional and molecular imaging approaches that are currently not feasible using inhaled HP (129)Xe.

SUBMITTER: Cleveland ZI

PROVIDER: S-EPMC3283644 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Publications

In vivo MR imaging of pulmonary perfusion and gas exchange in rats via continuous extracorporeal infusion of hyperpolarized 129Xe.

Cleveland Zackary I ZI Möller Harald E HE Hedlund Laurence W LW Nouls John C JC Freeman Matthew S MS Qi Yi Y Driehuys Bastiaan B

PloS one 20120221 2

<h4>Background</h4>Hyperpolarized (HP) (129)Xe magnetic resonance imaging (MRI) permits high resolution, regional visualization of pulmonary ventilation. Additionally, its reasonably high solubility (>10%) and large chemical shift range (>200 ppm) in tissues allow HP (129)Xe to serve as a regional probe of pulmonary perfusion and gas transport, when introduced directly into the vasculature. In earlier work, vascular delivery was accomplished in rats by first dissolving HP (129)Xe in a biological ...[more]

PMID: 22363613

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Project description:PURPOSE:To perform magnetic resonance imaging (MRI), human lung imaging, and quantification of the gas-transfer dynamics of hyperpolarized xenon-129 (HPX) from the alveoli into the blood plasma. MATERIALS AND METHODS:HPX MRI with iterative decomposition of water and fat with echo asymmetry and least-square estimation (IDEAL) approach were used with multi-interleaved spiral k-space sampling to obtain HPX gas and dissolved phase images. IDEAL time-series images were then obtained from ten subjects including six normal subjects and four patients with pulmonary emphysema to test the feasibility of the proposed technique for capturing xenon-129 gas-transfer dynamics (XGTD). The dynamics of xenon gas diffusion over the entire lung was also investigated by measuring the signal intensity variations between three regions of interest, including the left and right lungs and the heart using Welch's t test. RESULTS:The technique enabled the acquisition of HPX gas and dissolved phase compartment images in a single breath-hold interval of 8 s. The y-intersect of the XGTD curves were also found to be statistically lower in the patients with lung emphysema than in the healthy group (p?<?0.05). CONCLUSION:This time-series IDEAL technique enables the visualization and quantification of inhaled xenon from the alveoli to the left ventricle with a clinical gradient strength magnet during a single breath-hold, in healthy and diseased lungs. KEY POINTS:• The proposed hyperpolarized xenon-129 gas and dissolved magnetic resonance imaging technique can provide regional and temporal measurements of xenon-129 gas-transfer dynamics. • Quantitative measurement of xenon-129 gas-transfer dynamics from the alveolar to the heart was demonstrated in normal subjects and pulmonary emphysema. • Comparison of gas-transfer dynamics in normal subjects and pulmonary emphysema showed that the proposed technique appears sensitive to changes affecting the alveoli, pulmonary interstitium, and capillaries.

Project description:PurposeTo evaluate the safety and tolerability of inhaling multiple 1-L volumes of undiluted hyperpolarized xenon 129 ((129)Xe) followed by up to a 16-second breath hold and magnetic resonance (MR) imaging.Materials and methodsThis study was approved by the institutional review board and was HIPAA compliant. Written informed consent was obtained. Forty-four subjects (19 men, 25 women; mean age, 46.1 years ± 18.8 [standard deviation]) were enrolled, consisting of 24 healthy volunteers, 10 patients with chronic obstructive pulmonary disease (COPD), and 10 age-matched control subjects. All subjects received three or four 1-L volumes of undiluted hyperpolarized (129)Xe, followed by breath-hold MR imaging. Oxygen saturation, heart rate and rhythm, and blood pressure were continuously monitored. These parameters, along with respiratory rate and subjective symptoms, were assessed after each dose. Subjects' serum biochemistry and hematology were recorded at screening and at 24-hour follow-up. A 12-lead electrocardiogram (ECG) was obtained at these times and also within 2 hours prior to and 1 hour after (129)Xe MR imaging. Xenon-related symptoms were evaluated for relationship to subject group by using a ?(2) test and to subject age by using logistic regression. Changes in vital signs were tested for significance across subject group and time by using a repeated-measures multivariate analysis of variance test.ResultsThe 44 subjects tolerated all xenon inhalations, no subjects withdrew, and no serious adverse events occurred. No significant changes in vital signs (P > .27) were observed, and no subjects exhibited changes in laboratory test or ECG results at follow-up that were deemed clinically important or required intervention. Most subjects (91%) did experience transient xenon-related symptoms, most commonly dizziness (59%), paresthesia (34%), euphoria (30%), and hypoesthesia (30%). All symptoms resolved without clinical intervention in 1.6 minutes ± 0.9.ConclusionInhalation of hyperpolarized (129)Xe is well tolerated in healthy subjects and in those with mild or moderate COPD. Subjects do experience mild, transient, xenon-related symptoms, consistent with its known anesthetic properties.

Project description:ObjectivesWe developed a novel human cadaveric perfusion model with continuous extracorporeal femoral perfusion suitable for performing intra-individual comparison studies, training of interventional procedures and preclinical testing of endovascular devices. Objective of this study was to introduce the techniques and evaluate the feasibility for realistic computed tomography angiography (CTA), digital subtraction angiography (DSA) including vascular interventions, and intravascular ultrasound (IVUS).MethodsThe establishment of the extracorporeal perfusion was attempted using one formalin-fixed and five fresh-frozen human cadavers. In all specimens, the common femoral and popliteal arteries were prepared, introducer sheaths inserted, and perfusion established by a peristaltic pump. Subsequently, we performed CTA and bilateral DSA in five cadavers and IVUS on both legs of four donors. Examination time without unintentional interruption was measured both with and without non-contrast planning CT. Percutaneous transluminal angioplasty and stenting was performed by two interventional radiologists on nine extremities (five donors) using a broad spectrum of different intravascular devices.ResultsThe perfusion of the upper leg arteries was successfully established in all fresh-frozen but not in the formalin-fixed cadaver. The experimental setup generated a stable circulation in each procedure (ten upper legs) for a period of more than six hours. Images acquired with CT, DSA and IVUS offered a realistic impression and enabled the sufficient visualization of all examined vessel segments. Arterial cannulating, percutaneous transluminal angioplasty as well as stent deployment were feasible in a way that is comparable to a vascular intervention in vivo. The perfusion model allowed for introduction and testing of previously not used devices.ConclusionsThe continuous femoral perfusion model can be established with moderate effort, works stable, and is utilizable for medical imaging of the peripheral arterial system using CTA, DSA and IVUS. Therefore, it appears suitable for research studies, developing skills in interventional procedures and testing of new or unfamiliar vascular devices.

Dataset Information

In vivo MR imaging of pulmonary perfusion and gas exchange in rats via continuous extracorporeal infusion of hyperpolarized 129Xe.

Background

Methods and principal findings

Conclusions

Publications

In vivo MR imaging of pulmonary perfusion and gas exchange in rats via continuous extracorporeal infusion of hyperpolarized 129Xe.

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