이 연구는 NIH 보조금 R01HL159898 및 R01HL142258의 지원을 받았습니다.

Hyperpolarized Xenon-129 MRI를 이용한 폐 기능 평가

<ol>
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저자는 공개할 이해 상충이 없습니다.

HXe CSSR MR 분광법은 기존의 다른 진단 양식(24)을 사용하여 생체 내에서 정량화하기 어렵거나 불가능한 여러 폐 기능 지표를 평가하기 위한 강력한 기술이다. 그럼에도 불구하고, 획득 및 후속 데이터 분석은 살아있는 피험자에서 완전히 달성할 수 없는 생리학적 조건 및 기술적 매개변수에 대한 특정 가정을 기반으로 합니다. 이러한 제한 사항과 추출된 메트릭의 해석에 미...

과분극 제논-129(HXe) 자기 공명 영상(MRI)1은 폐 구조, 기능 및 가스 교환 과정에 대한 고유한 통찰력을 제공하는 기술입니다. 스핀 교환 광학 펌핑을 통해 크세논 가스의 자화를 극적으로 증폭시킴으로써 HXe MRI는 열 편광 된 크세논 MRI 2,3,4,5,6에 비해 신호 대 잡음비에서 큰 개선을 달성합니다. 이러한 과분극은 기존의 열분극 MRI7로는 검출할 수 없는 폐 조직과 혈액으로의 크세논 가스 흡수를 직접 시각화하고 정량화할 수 있습니다.
화학적 이동 포화 회복 (CSSR) MR 분광법 8,9,10,11,12,13은 가장 가치있는 HXe MRI 기술 중 하나로 입증되었습니다. CSSR은 주파수 특정 무선 주파수(RF) 펄스를 사용하여 폐 조직과 혈액에 용해된 크세논의 자화를 선택적으로 포화시키는 것을 포함합니다. ms 단위의 시간 척도로 영공에서 새로운 과분극된 크세논 가스와 교환할 때 용해상(DP) 신호의 후속 복구는 폐 실질에 대한 중요한 기능 정보를 제공합니다.
2000 년대 초반의 개발 이후 CSSR 분광법의 기술은 점진적으로 개선되었습니다 14,15,16,17,18,19,20,21,22,23. 또한, 크세논 흡수 곡선 모델링의 발전으로 폐포벽 두께 및 폐 통과 시간 10,24,25,26과 같은 특정 생리학적 매개변수를 추출할 수 있게 되었습니다. 연구에 따르면 만성 폐쇄성 폐질환(COPD)18,27,28, 섬유증29 및 방사선 유발 폐 손상30,31을 포함한 다양한 폐 질환뿐만 아니라 임상적으로 건강한 흡연자27에서 발견되는 폐 이상 형태의 폐 미세 구조 및 가스 교환 효율의 미묘한 변화에 대한 CSSR의 민감성이 나타났습니다. CSSR 분광법은 또한 심장 주기(32) 동안 박동성 혈류에 해당하는 DP 신호의 진동을 감지하기 위해 민감한 것으로 입증되었다.
상당한 진전이 이루어졌지만 임상 MRI 시스템에 CSSR 분광법을 구현하는 데 실질적인 어려움이 남아 있습니다. 10초에 가까운 1회 투여 호흡 유지를 요구하는 스캔 시간은 소아 피험자33,34 또는 중증 폐 질환 환자35,36에게 너무 길 수 있다. 또한, 이 기술은 포화 지연 시간의 순서 또는 용해 위상 포화의 효율과 같은 획득 파라미터가 적절하게 최적화되지 않은 경우 측정 편향에 취약합니다21. 이러한 한계를 해결하고 더 광범위한 연구 커뮤니티에서 CSSR에 더 쉽게 접근할 수 있도록 하려면 현재 개발 중인 기존의 숨참기 및 자유 호흡 획득 모두에 대한 명확한 단계별 프로토콜이 필요합니다.
이 논문의 목적은 HXe 가스를 사용하여 최적화된 CSSR MR 분광법을 수행하기 위한 자세한 방법론을 제시하는 것입니다. 이 프로토콜은 제논 가스의 분극 및 전달, RF 펄스 교정, 시퀀스 파라미터 선택, 피사체 준비, 데이터 수집 및 데이터 분석의 주요 단계를 다룹니다. 실험 결과의 예가 제공됩니다. 이 포괄적인 가이드가 여러 기관에 걸친 CSSR 구현의 기초 역할을 하고 다양한 폐 질환에서 폐 미세 구조 변화를 정량화하기 위한 이 기술의 잠재력을 최대한 실현하는 데 도움이 되기를 바랍니다.

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quantitative measure of lung structure and function obtained from hyperpolarized xenon spectroscopy

과분극 제논-129(HXe) 자기 공명 영상(MRI)은 폐 환기 패턴, 가스 확산, 폐 실질에 의한 크세논 흡수 및 기타 폐 기능 지표에 대한 2차원 또는 3차원 지도를 얻기 위한 도구를 제공합니다. 그러나 시간적 해상도를 위해 공간적 변환기를 사용함으로써 ms 시간 척도에서 폐 크세논 가스 교환을 추적할 수도 있습니다. 이 기사에서는 이러한 기술 중 하나인 CSSR(Chemical Shift Saturation Recovery) MR 분광법에 대해 설명합니다. 이는 모세혈관 혈액량, 중격벽 두께 및 폐포의 표면 대 부피 비율을 평가하는 데 어떻게 사용할 수 있는지 보여줍니다. 적용된 무선 주파수 펄스(RF)의 플립 각도는 신중하게 보정되었습니다. 피험자에게 가스를 투여하기 위해 단일 용량 숨 참기 및 다중 용량 자유 호흡 프로토콜이 사용되었습니다. 흡입된 크세논 가스가 허파꽈리에 도달하면 일련의 90° RF 펄스가 적용되어 폐 실질에서 축적된 크세논 자화의 최대 포화를 보장했습니다. 가변적인 지연 시간에 따라, 폐포 가스 부피와 폐의 조직 구획 사이의 가스 교환으로 인한 크세논 신호의 재성장을 정량화하기 위해 스펙트럼을 획득했습니다. 그런 다음 이러한 스펙트럼은 복잡한 pseudo-Voigt 함수를 3개의 주요 피크에 피팅하여 분석되었습니다. 마지막으로, 지연 시간 종속 피크 진폭을 1차원 분석 가스 교환 모델에 장착하여 생리학적 매개변수를 추출했습니다.

Hyperpolarized Xenon-129 (HXe) magnetic resonance imaging (MRI)1 is a technique that offers unique insights into lung structure, function, and gas exchange processes. By dramatically amplifying the magnetization of Xenon gas through spin-exchange optical pumping, HXe MRI achieves an order-of-magnitude improvement in signal-to-noise ratio compared to thermally polarized Xenon MRI2,3,4,5,6. This hyperpolarization enables the direct visualization and quantification of Xenon gas uptake into lung tissue and blood, which would otherwise be undetectable with conventional thermally polarized MRI7.
Chemical shift saturation recovery (CSSR) MR spectroscopy8,9,10,11,12,13 has proven to be one of the most valuable HXe MRI techniques. CSSR involves selectively saturating the magnetization of Xenon dissolved in lung tissue and blood using frequency-specific radiofrequency (RF) pulses. The subsequent recovery of the dissolved-phase (DP) signal as it exchanges with fresh hyperpolarized Xenon gas in the airspaces on a timescale of ms offers important functional information about the lung parenchyma.
Since its development in the early 2000s, the techniques behind CSSR spectroscopy have been progressively refined14,15,16,17,18,19,20,21,22,23. Further, advances in modeling Xenon uptake curves have enabled the extraction of specific physiological parameters, such as alveolar wall thickness and pulmonary transit times10,24,25,26. Studies have shown CSSR&#39;s sensitivity to subtle changes in lung microstructure and gas exchange efficiency in the form of pulmonary abnormalities found in clinically healthy smokers27, as well as in a range of lung diseases, including chronic obstructive pulmonary disease (COPD)18,27,28, fibrosis29, and radiation-induced lung injury30,31. CSSR spectroscopy has also been demonstrated to be sensitive to detect oscillations in the DP signal corresponding to pulsatile blood flow during the cardiac cycle32.
While significant progress has been made, practical challenges remain in implementing CSSR spectroscopy on clinical MRI systems. Scan times requiring single-dose breath holds approaching 10 s may be too long for pediatric subjects33,34 or patients with severe lung disease35,36. Additionally, the technique is susceptible to measurement biases if acquisition parameters such as the order of the saturation delay times or the efficacy of the dissolved-phase saturation are not properly optimized21. To address these limitations and make CSSR more accessible to the broader research community, clear, step-by-step protocols for both conventional breath hold and free-breathing acquisitions, currently under development, are needed.
The objective of this paper is to present a detailed methodology for performing optimized CSSR MR spectroscopy using HXe gas. The protocol will cover polarization and delivery of the Xenon gas, RF pulse calibration, sequence parameter selection, subject preparation, data acquisition, and key steps in data analysis. Examples of experimental results will be provided. It is hoped that this comprehensive guide will serve as a foundation for CSSR implementations across sites and help realize the full potential of this technique for quantifying lung microstructural changes in a range of pulmonary diseases.

저자 스포트라이트: 자유 호흡 과분극 Xenon-129 MRI를 통한 폐 질환 연구 발전

Quantitative Measure of Lung Structure and Function Obtained from Hyperpolarized Xenon Spectroscopy(과분극 크세논 분광법에서 얻은 폐 구조 및 기능의 정량적 측정)

Our research focuses on using hyperpolarizing on 129 MRI technology to assess pulmonary function and to investigate lung diseases. The main objective is to see how this imaging technique can lead to better detection, understanding, and tracking of different lung conditions. Most hyperpolarized lung MR imaging is performed during a breath hold.We believe that pulmonary function quantified under such an artificial condition, may not fully reflect gas exchange during regular respiration, and we are testing new free breathing measurements that do not require any breath hold. Current challenges include the optimization of the CSSR acquisition technique for consistency and accuracy in the face of physiological variation and patient compliance. Severely ill or pediatric patients struggle with maintaining lengthy breath holds.The CSSR heart technique appears particularly sensitive to changes in alveolar septal wall thickness. As we and others in the field of demonstrated, alveolar wall thickening can indicate the presence of interstitial edema, inflammation, or pulmonary fibrosis. All metrics derived from CSSR spectroscopy acquisitions are currently based on the temporal dynamics of the signal amplitudes.In the future though, we hope to include changes in peak shape and center frequency in the analysis to obtain a more complete picture of the ongoing gas exchange processes.

그림 2는 500mL의 제논 용량을 흡입한 후 숨을 참는 동안 인간의 폐에서 관찰되는 전형적인 제논 스펙트럼을 보여줍니다. 스펙트럼은 약 0ppm의 GP 공명과 약 197ppm의 막 피크와 약 217ppm의 적혈구 피크로 구성된 DP 영역의 두 가지 별개의 영역을 표시합니다. 상대적 피크 진폭은 RF 여기 펄스의 모양, 지속 시간, 중심 주파수, 포화와 여기 사이의 지연 시간을 포함한 여러 요인에 따?...

Watch this Scientific Journal Video about Author Spotlight: Advancing Lung Disease Research with Free-Breathing Hyperpolarized Xenon-129 MRI at JoVE.com

이 원고는 과분극 Xenon-129 화학적 이동 포화 회복(CSSR)을 사용하여 폐 가스 교환을 추적하고, 겉보기 폐포 중격 벽 두께를 평가하고, 표면 대 부피 비율을 측정하기 위한 자세한 프로토콜을 제시합니다. 이 방법은 폐 질환을 진단하고 모니터링할 수 있는 잠재력을 가지고 있습니다.

Hyperpolarized Xenon-129 (HXe) magnetic resonance imaging (MRI) provides tools for obtaining 2- or 3-dimensional maps of lung ventilation patterns, gas ...

우리의 연구는 폐 기능을 평가하고 폐 질환을 조사하기 위해 129 MRI 기술에 과분극을 사용하는 데 중점을 둡니다. 주요 목표는 이 이미징 기술이 어떻게 다양한 폐 상태를 더 잘 감지, 이해 및 추적할 수 있는지 확인하는 것입니다. 대부분의 과분극 폐 MR 영상은 숨을 참는 동안 수행됩니다.우리는 이러한 인위적인 조건에서 정량화된 폐 기능이 정상적인 호흡 중 가스 교환을 완전히 반영하지 못할 수 있다고 생각하며, 숨을 참을 필요가 없는 새로운 자유 호흡 측정을 테스트하고 있습니다. 현재 과제로는 생리학적 변화와 환자 순응도에 직면하여 일관성과 정확성을 유지하기 위한 CSSR 획득 기법의 최적화가 있습니다. 중증 환자나 소아 환자는 긴 호흡 참기를 유지하는 데 어려움을 겪습니다.CSSR 심장 기술은 폐포 중격 벽 두께의 변화에 특히 민감한 것으로 보입니다. 우리와 이 분야의 다른 사람들이 입증한 바와 같이, 폐포 벽이 두꺼워지는 것은 간질성 부종, 염증 또는 폐 섬유증의 존재를 나타낼 수 있습니다. CSSR 분광법 획득에서 파생된 모든 메트릭은 현재 신호 진폭의 시간 역학을 기반으로 합니다.그러나 앞으로는 진행 중인 가스 교환 과정에 대한 보다 완전한 그림을 얻기 위해 피크 모양과 중심 주파수의 변화를 분석에 포함하기를 희망합니다.

quantitative-measure-lung-structure-function-obtained-from

Research

JoVE Journal

Medicine

Quantitative Measure of Lung Structure and Function Obtained from Hyperpolarized Xenon Spectroscopy

380 조회수.  University of Pennsylvania. 우리의 연구는 폐 기능을 평가하고 폐 질환을 조사하기 위해 129 MRI 기술에 과분극을 사용하는 데 중점을 둡니다. 주요 목표는 이 이미징 기술이 어떻게 다양한 폐 상태를 더 잘 감지, 이해 및 추적할 수 있는지 확인하는 것입니다. 대부분의 과분극 폐 MR 영상은 숨을 참는 동안 수행됩니다.우리는 이러한 인위적인 조건에서 정량화된 폐 기능이 정상적인 호흡 중 가스 교환...

비디오: 저자 스포트라이트: 자유 호흡 과분극 Xenon-129 MRI를 통한 폐 질환 연구 발전

Hyperpolarized Xenon-129 (HXe) magnetic resonance imaging (MRI) provides tools for obtaining 2- or 3-dimensional maps of lung ventilation patterns, gas diffusion, Xenon uptake by lung parenchyma, and other lung function metrics. However, by trading spatial for temporal resolution, it also enables tracing of pulmonary Xenon gas exchange on a ms timescale. This article describes one such technique, chemical shift saturation recovery (CSSR) MR spectroscopy. It illustrates how it can be used to assess capillary blood volume, septal wall thickness, and the surface-to-volume ratio in the alveoli. The flip angle of the applied radiofrequency pulses (RF) was carefully calibrated. Single-dose breath-hold and multi-dose free-breathing protocols were employed for administering the gas to the subject. Once the inhaled Xenon gas reached the alveoli, a series of 90&#176; RF pulses was applied to ensure maximum saturation of the accumulated Xenon magnetization in the lung parenchyma. Following a variable delay time, spectra were acquired to quantify the regrowth of the Xenon signal due to gas exchange between the alveolar gas volume and the tissue compartments of the lung. These spectra were then analyzed by fitting complex pseudo-Voigt functions to the three dominant peaks. Finally, the delay time-dependent peak amplitudes were fitted to a one-dimensional analytical gas-exchange model to extract physiological parameters.

The manuscript presents a detailed protocol for using hyperpolarized Xenon-129 chemical shift saturation recovery (CSSR) to trace pulmonary gas exchange, assess the apparent alveolar septal wall thickness, and measure the surface-to-volume ratio. The method has the potential to diagnose and monitor lung diseases.

연구

의학

Patient Preparation and Subject Training for Hyperpolarized Xenon MRI

To begin, set up the physiological monitoring system to record breathing curves and real-time gas analysis during imaging. Connect and test the MRI room headphones with the audio signal that guides the subject using an inhale-exhale audio recording. Adjust the playback speed of the audio track.Inhale.Exhale.Based on the normal breathing rate of each subject.Inhale.Exhale. Next, prepare the scanner bed with a clean headrest, leg support pillow and blanket. Place the unfastened Xenon 129 chest vest coil on the table of the MRI scanner and insert the connector plug of the coil.For a free breathing study, introduce the subject to the inhale-exhale voice recording for synchronized breathing during imaging. Lead the subject into the MRI room and position them on the scanner bed, lying on top of the open xenon vest coil. Once the subject is positioned, fasten the Velcro straps so that the vest coil is closed, but does not constrict the subject's chest.For a free breathing study, place a face mask with a pneumatac over the patient's face. Tighten the straps so the mask fits snugly over the nose and mouth without being too tight. After fitting, remove the mask and set it aside for later, leaving the straps behind the subject's head.Then place two pulse oximeters on both index fingers to continuously monitor heart rate and blood oxygen saturation during the study. Place MRI compatible headphones over the subject's ears. Move the MRI scanner table into the magnet bore so the subject's lungs are positioned in the center of the field of view.

Hyperpolarized Xenon MRI에 대한 환자 준비 및 피험자 교육

Polarizing Xenon-129 for Hyperpolarized Xenon Spectroscopy

To begin, heat up the xenon polarizer approximately 2.5 hours before the study starts. Thread the connector two of a 250 milliliter specialized polyvinyl fluoride or PVF bag through a ceiling clip. Attach the bag to one of the four available polarizer dispense ports.On the polarizer touchscreen, select the enriched xenon tank. Set the flow rate to medium and the polarization volume to 250 milliliters. Then press the start button to initiate the polarization process.Once the polarized xenon gas has been dispensed, the polarizer's touchscreen will display a message to remove the bag. Pinch the connector tube of the specialized PVF bag shut with the ceiling clip, and then disconnect the bag to place it inside the bore of the MRI scanner.

Hyperpolarized Xenon Spectroscopy를 위한 Polarizing Xenon-129

Performing Hyperpolarized Xenon-129 Inhalation for Chemical Shift Saturation Recovery (CSSR) Measurement

To perform xenon inhalation using the breath hold method, place a nose clip on the nose of the subject to facilitate breathing through the mouth. At the end of a normal exhalation to functional residual capacity, insert the mouthpiece of the xenon bag into the subject's mouth. Allow the subject to inhale 500 milliliters of xenon gas from the xenon bag.Then remove the mouthpiece and instruct the subject to continue inhaling room air until the lungs are full. At the end of inhalation, ask the subject to raise their thumb. Request the nurse coordinator to verbally convey this information to the scanner operator to start the pulse sequence.After the data acquisition period, instruct the subject to return to normal breathing. Move the subject out of the MRI scanner. Place a face mask over their nose and mouth.Connect the hoses to the mask, and then connect the pre-fitted straps from behind the head to the mask and secure it in place. Move the subject to its original position inside the MRI scanner. Once the subject follows the breathing protocol, ask the nurse coordinator to inform the MRI operator to initiate data acquisition.The nurse coordinator then opens the valves on the gas delivery system and the subject inhales 50 milliliters of hyperpolarized xenon 1-29 mixed with the airflow inside the breathing mask. Instruct the subject to continue breathing for approximately 10 breaths until the volume of xenon gas has been used up for the imaging protocol. Load the CSSR pulse sequence for free breathing.Set the acquisition frequency according to the hyperpolarized xenon gas phase frequency determined during the calibration scan. Adjust the reference voltage to match the value obtained from the calibration scan. Select the wait for user option, or its equivalent, for sequence execution, following the system vendor's operating instructions.Start the MRI scanner sequence. The scanner will pause for user input before data acquisition. Once the nurse coordinator switches the hyperpolarized xenon gas or air mixture, start data acquisition.Ensure the sequence is already running before the subject inhales the first dose of xenon gas. After the three minute data acquisition, or exhaustion of hyperpolarized xenon gas, remove the subject from the MRI scanner. In the young, healthy female, the membrane signal increases rapidly due to the quick filling of thin walls.In the older, lung transplant recipient, the membrane signal rises more gradually reflecting the longer time required to fill the thicker septal walls.