phase-resolved functional lung mri procedure for quantitative assessment of perfusion and ventilation

<meta charset="utf8"></head><body>疾患の検出とモニタリングのための高度な肺イメージング

The respiratory system, with its intricate mechanisms, is vulnerable to various diseases. Prominently, chronic respiratory conditions such as chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF), and chronic thromboembolic pulmonary hypertension (CTEPH) considerably reduce life expectancy1. As a result, early diagnosis, monitoring, and therapeutic response assessment have become paramount.
Pulmonary function tests (PFTs) can derive global lung function parameters like the Tiffeneau-Pinelli index, defined as the ratio of the forced expiratory volume in one second (FEV1) and forced vital capacity (FVC)2. Such parameters are well established in the clinical routine but lack regional information and require a high level of patient compliance. In this regard, imaging can offer additional insights and possibilities for more sensitive parameters. Computed tomography (CT) offers high-resolution imaging of parenchymal morphology, and recent techniques like parametric-response mapping also retrieve functional information3. Nevertheless, single photon emission computed tomography (SPECT) remains the current gold standard for depicting ventilation and perfusion (V/Q) in the lung4. Common to all, the mentioned imaging modalities require exposure to ionizing radiation, which needs special consideration in cases of monitoring and vulnerable groups. Consequently, there is an ongoing effort to promote MRI as an alternative modality.
Inherently, the lung is a challenging organ for MRI due to its low proton density and fast signal decay5. Among the multitude of approaches, the most widespread solutions include the use of hyperpolarized gas (e.g., 129Xe MRI) for ventilation6 and intravenous gadolinium-based contrast agent application for perfusion depiction7. These methods offer a high signal-to-noise (SNR) ratio and are widely considered gold standard methods in the MR community. A more recent approach avoids the application of any contrast agent and is feasible with conventional proton MR in free breathing with a total acquisition time of ~1 min/slice. Thus, potential adverse events and recently debated long-term effects of contrast agents are avoided and easier dissemination without the requirement for additional hyperpolarization and multi-nuclear hardware is enabled. Additionally, the problem of finding an adequate inflation state, which can affect the derived ventilation defect values8 is avoided by the free-breathing acquisition.
This indirect MR signal-based approach was first introduced by Zapke et al. who utilized the reciprocal relationship of proton-weighted signal S and lung volume V: S~1/V.9 It is based on the process of transforming images acquired in free-breathing to one common inflation state (typically in an intermediate position between end-expiration and end-inspiration), thereby compensating for motion and allowing to analyze the signal time series in each voxel. Thereafter, a ventilation measurement can be derived from these so-called registered images by using equation (1) by Klime&#353; et al.10:
<img alt="Equation 1" src="/files/ftp_upload/66380/66380eq01.jpg" style="margin: auto;" />&#160; &#160; &#160;(1)
With the volumes/signals in inspiration (Insp), expiration (Exp), and registered state (Reg). Thereafter, the method was expanded by introducing Fourier Decomposition to differentiate between signal modulations associated with breathing frequency (ventilation) and pulse frequency (perfusion) and therefore, derive a perfectly spatially matched V/Q map from one acquisition11. This is made possible by the typical gap between breathing and heart frequencies, so that both components which are on top of each other in the time domain are effectively discriminated in the frequency domain by Fourier analysis. After the transition from low-field (0.35T) to 1.5T with an optimized balanced steady-state free precession sequence (bSSFP)12, this method started to gain more attention with several follow-up studies13,14,15.
Since breathing and pulse are subject to variability and commercially available bSSFP (gradient compensated) imaging at 1.5T can result in substantial banding artifacts (clear lines of signal void), a related method was proposed with spoiled gradient echo sequence (SPGRE) in combination with broad low-pass and high-pass filtering16,17. This captures the more complex spectrum of real breathing- and pulse-related modulations. The following calculation of the amplitude in the time domain avoids the necessity to select one specific frequency peak. Further optimization was achieved by splitting the typical one-step registration towards one reference state into two separate steps. Thereby the fact that during free-breathing a range of different respiration phases are acquired between end-inspiration and end-expiration with varying degrees of required deformation towards a fixed state is utilized. After choosing several groups and identifying the group of the individual images the following procedure is performed: 1) Registration inside the respective respiration state group, 2) Step-by-Step inter-group registration from one adjacent group to the next (e.g., 1-&#62;2, 2-&#62;3,&#8230;) to the group representing the reference group. This approach was further expanded by phase estimation for each image to establish a higher apparent temporal resolution to facilitate the analysis of ventilation and perfusion dynamics, leading to the phase-resolved functional lung (PREFUL) MR terminology to differentiate this branch from other related techniques18. Follow-up studies made use of the additional information provided by the full respiration and cardiac cycles and showed potentially increased sensitivity of such parameters19,20,21.
Validation with the gold standard SPECT revealed a dice coefficient of &#8805;67% for defect regions22, and more direct ventilation measurement with 129Xe showed ventilation defect percentages correlation &#8805;62% in a mixed COPD/CF/healthy cohort23 and 84% in a CF multi-center, multi-vendor cohort24, which also demonstrated a similar correlation to lung clearance index of PREFUL and 129Xe (r = 0.82 and r = 0.91). The perfusion analysis of the same study showed that there were no significant differences in spatial overlap with DCE among the evaluated centers25. Concordance with DCE and agreement of PREFUL results between centers was also reported for a prospective sub-study including nine centers26. A reproducibility analysis in COPD patients resulted in a coefficient of variation below 15% for all parameters27. Current studies suggest that the FVL parameter has higher predictive power and sensitivity to detect treatment changes compared to the &#34;static&#34; ventilation parameter, which only takes the end-inspiratory and end-expiratory phases into account. Responsiveness to treatment with regional flow-volume loop (FVL) measurements was demonstrated after inhaler treatment with indacaterol-glycopyrronium (IND/GLY) in COPD28. In concordance, the FVL parameter predicted graft loss in double-lung transplant patients, whereas spirometry could not (P = .02 vs. P = 0.33)29. First feasibility studies show that functional pulmonary imaging with PREFUL can be realized in free-breathing infants and neonates with standard clinical MRI hardware30,31. Glandorf et al. compared PREFUL parameters at 1.5T and 3T (SPGRE sequence) and found no significant differences for most parameters, which were highly reproducible despite the difference in field strength32. This might be an important advantage, as not every site has access to 1.5T or lower field strength scanners. Recently, the feasibility and detection of persistent symptoms after COVID-19 infection at 0.55T was demonstrated by evaluating bSSFP data with PREFUL33.
In summary, despite being a relatively novel technique, PREFUL has been extensively studied. Important criteria such as validation with more direct and established measurements, reproducibility, sensitivity for pathology, and responsiveness for treatment and progression changes were assessed. Nevertheless, still, only a few specialized centers are using this technique despite the low technological requirements. Therefore, the aim of this work is to summarize the latest methodology of PREFUL MR in written and visual form. This information can be used to establish this technique in more centers and thus, in the long-term, lead to a more mature technique.

<meta charset="utf8"></head><body>著者スポットライト:包括的な肺機能分析のための診断戦略とバイオマーカー開発の強化

肺換気および灌流 (V/Q) 評価のための位相分解機能肺 MRI

灌流と換気の定量的評価のための位相分解機能肺MRI手順。 

phase-resolved-functional-lung-mri-procedure-for-quantitative

Research

JoVE Journal

Medicine

Phase-Resolved Functional Lung MRI Procedure for Quantitative Assessment of Perfusion and Ventilation

73 ビュー. まず、患者が到着したときに、手順の磁気特性とリスクについて患者を教育します。患者にすべての個人用金属アイテムを取り除くように指示します。.次に、0.55T、1.5T、または3Tシステム上で患者を仰臥位に向けます。安全性と快適さのために、聴覚保護具、緊急用ベル、パッド、毛布を用意してください。次に、マルチチャンネルフレッ...

ビデオ: 灌流と換気の定量的評価のための位相分解機能肺MRI手順。 

Phase-Resolved Functional Lung MRI for Pulmonary Ventilation and Perfusion (V/Q) Assessment

Fourier decomposition is a contrast agent-free 1H MRI method for lung perfusion (Q) and ventilation (V) assessment. After image registration, the time series of each voxel is analyzed with regard to the cardiac and breathing frequency components.
Using a standard 2D spoiled gradient-echo sequence with a temporal resolution of ~300 ms, an image-sorting algorithm was developed to produce phase-resolved functional lung imaging (PREFUL) with an increased temporal resolution. Thus, it is feasible to evaluate regional flow volume loops (FVL) during tidal volume breathing and depict the propagation of the pulse wave during the cardiac cycle. This method can be applied at 1.5T or 3T with standard MR hardware without the necessity for sequence programming, as the described protocol can be implemented with the default SPGRE sequence on most systems.
PREFUL ventilation MRI has been validated using 129Xe and 19F gas imaging with good regional agreement. Perfusion-weighted PREFUL MRI has been validated using SPECT as well as dynamic contrast enhanced (DCE) MRI. PREFUL has been tested in a dual center dual vendor setting and is currently applied in several ongoing multicenter trials. Furthermore, it is feasible across a range of field strengths (0.55T-3T) and different age groups, including newborns.
Quantitative V/Q PREFUL MRI has been used in patients with cystic fibrosis, chronic obstructive pulmonary disease, chronic thromboembolic pulmonary hypertension, and corona virus disease-2019 to quantify disease and monitor treatment change after therapy. Furthermore, PREFUL V/Q imaging has been shown to predict transplant loss due to chronic lung allograft dysfunction in patients after lung transplantation. In summary, PREFUL MRI is a validated technique for quantitative ventilation and pulmonary pulse wave/perfusion imaging for regional pulmonary disease detection, quantification, and treatment monitoring with potential added value to the current clinical routine.

Here, we describe the implementation of phase-resolved functional lung MRI as a contrast-agent-free proton MR technique for the assessment of pulmonary ventilation and perfusion dynamics. Validated and applicable across different field strengths and age groups, it could enhance clinical decision-making in the future by aiding in disease quantification and therapy monitoring.

Fourier decomposition is a contrast agent-free 1H MRI method for lung perfusion (Q) and ventilation (V) assessment. After image registration, the time ...