Hyperpolarized 129Xe MR imaging of lung

Magnetic Resonance Imaging (MRI) has a range of applications in medical diagnosis, and more than 25,000 scanners are estimated to be in use worldwide. However, lung imaging suffers from some technical challenges, limiting its application in pulmonary disease diagnosis and treatment.

 

Due to low proton density, movement and high susceptibility difference between air and tissue, conventional proton MRI struggles to image lung tissue and function. These can be partially overcome by the introduction of contrast agents into the lung. Hyperpolarised gases are promising contrast agents for imaging lung structure and function. The two most common gasses are helium (3He) and xenon (129Xe) isotopes. Helium isotopes are challenging and expensive to obtain, and do not provide significant functional readouts. Xenon can be challenging to work with, but promises novel physiological measurements not previously feasible. This resulting technique, termed hyperpolarized 129Xe MR imaging, has revolutionised the field of functional lung imaging.

 

Five years ago, an Australian Research Council (ARC) grant was awarded to researchers at Monash Biomedical Imaging (MBI) and ANSTO to design and build a machine that could reliably produce hyperpolarized xenon. In this project, Dr Wai Tung Lee and NIF Facility Fellow Dr Gang Zheng have teamed up to develop a new multimodal technology capable of high-quality investigations of the human lungs. While Dr Lee, of ANSTO, was responsible for the construction of the polarizer and production of polarized 129Xe for MR imaging, Dr Zheng, of Monash University, designed the MR experiments and adapted imaging protocols.

Figure 1. Schematic diagram of the polarizer system. Note: Some details omitted for clarity.

Hyperpolarized 129Xe (HP-Xe) gas was generated in a custom designed and constructed SEOP system at Monash Biomedical Imaging (Figure 1 and Figure 2). The system consists of a gas-polarizing unit and a gas injection and recycle unit. The core component of the gas-polarizing unit is an optical pumping cell (OPC) where the gas is polarized. The OPC is placed in an oven to regulate the amount of Rb vapour by maintaining a constant temperature between 60ºC-90ºC. The optical pumping process uses two 240W narrow-bandwidth lasers tuned to the Rb D1 transition wavelength of 794.7nm. Additional optics condition the laser light to circular polarization and shape the laser profile to fully illuminate the OPC. HP-Xe is produced in batches rather than using a continuous-flow process.

Figure 2. The spin-exchange-optical pumping system. A. Gas polarizing unit in Room 1; B. Gas injection and recycling unit in Room 2.

MR experiments were performed on a clinical 3T whole-body system (Skyra, Siemens Medical Solutions, Erlangen, Germany) with a broadband RF amplifier. HP-129Xe MRI was enabled using a bird-cage transmit/receive chest coil (RAPID Biomedical GmbH, Wuerzburg, Germany). A 2D-GRE sequence for X-nuclei MRI was used to image HP-Xe gas in lung. Proton channel images were acquired for the localization of the lung. The resonance frequency of 129Xe was set to 34.09 MHz on the 3T scanner. The human subject first quickly flushed his lung with pure nitrogen, and then immediately inhaled HP-Xe in the Tedlar bag. After inhalation of HP-Xe, the subject held their breath during the scan. The total imaging time was less than 10s.

 

Dr Zheng outlines the results to date, “We have successfully imaged gas-phase HP-129Xe in a range of phantoms, such as the Tedlar bag, syringe and the glass cell (Figure 3). We repeated the gas-phase imaging in both ex-vivo (Figure 4) and in-vivo lamb lungs (Figure 5). Imaging results supported that our polarizer can provide sufficient polarization for lung imaging. In 2019, we successfully performed a human experiment and a gas signal from the lungs was clearly identified (Figure 6). In addition, all studied showed a clear Rf peak of gaseous and dissolved xenon which should allow us to develop methods to assess lung function. We plan to study human pulmonary disease in the near future and hope to find additional collaborators to help translate this modality into clinical use.”

Gallery Notice : Images have either not been selected or couldn't be found

Construction of the hyperpolarizer is complete; it can routinely produce HP-129Xe for research use. The technique has successfully imaged HP-129Xe in phantoms, ex-vivo and in-vivo lamb lungs and a human lung. If you are considering lung research, please see more on the Monash website, or get in touch with Dr Gang Zheng to discuss your project needs.

 

 

Publications:

Zheng G, Lee WT, Tong X, et al., A SEOP Filling Station at the Monash Biomedical Imaging Centre. Conference on polarization in Noble gases (PiNG), 2017.

 

Zheng G, Lee WT, Tong X, et al., Phase imaging of hyperpolarized 129Xe gas in a human lung. ISMRM 2020, submitted on 6 Nov 2019.

 

 

Acknowledgements:

National Imaging Facility, ARC (Grant LE130100035); NHMRC (Grant APP606944); CASS Foundation; Monash Biomedical Imaging, ANSTO

 

This story was contributed by Dr Gang Zheng of the Monash University NIF Node.

 

Impact of surgical lymph node removal

The impact of surgical lymph node removal on metastatic disease and the response to immunotherapy

Surgical resection of cancer remains the frontline therapy for millions of cancer patients every year, but disease recurrence after surgery is common with a relapse rate of around 45% for lung cancer. Relapse rates are expected to decline, with new immunotherapies producing extraordinary successes in several solid cancers. Immunotherapy administered after surgery could potentially ‘mop up’ small persisting cancer deposits that lead to disease recurrences. However, uninvolved (tumour-free) draining lymph nodes are the primary ‘factory’ for generating anti-cancer T cell responses; hence, should they be removed, subsequent immunotherapy may be negatively impacted. The aim of this project is to determine in murine models if the response of metastatic disease to immunotherapy is reduced following tumour lymph node resection.

Dr Vanessa Fear of the School of Biomedical Sciences, at The University of Western Australia, is investigating if the response of metastatic disease to immunotherapy is reduced following tumour draining lymph node resection. To do this, the Tumour Immunology Group is using an AB1 Model of metastatic disease. Tumour progression is visualised using IVIS imaging and histology following resection to track the effectiveness of treatment regimes. Ultimately, the team will seek to determine the impact of lymph node removal at the time of tumour resection to subsequent immunotherapeutic outcomes.

Fig 1: IVIS imaging from AB1-HA tumour model. Mice received AB1-HA_LUC i.v. and lung tumour development monitored on the InVivo Imaging System (IVIS, Lumina II imager). At the imaged timepoints mice received intrapertioneal injections of luciferin (150µg/g) and tumour burden was measured on the IVIS in photons/sec (p/s). A, tumour progression day 14 to day 19.

The research project involves collaboration with the Centre for Microscopy, Characterisation and Analysis, the West Australian Node for the National Imaging Facility to image, visualise and characterise the development of lung metastatic disease using the IVIS Lumina II in vivo bioluminescence imager with the help of Living Image Software (Caliper Life Sciences).

Fig 2: IVIS imaging and histology from AB1-HA tumour model.Comparison of IVIS reading with lung H&E staining showing AB1-HA tumour from the same mouse. Tumour volume determined using FIJI software.

The team have completed preliminary studies determining a 55% metastatic disease onset after surgical resection of the primary tumour. Current investigations in tumour resection and lymph node resection indicate temporal changes in onset of metastatic disease compared to mice with intact lymph nodes.

Further investigations into the impact of lymph node resection on immunotherapy are underway. Future investigations will include other models including lung adenocarcinoma, melanoma, and breast cancer.

Collaborators

School of Medicine, the University of Western Australia

School of Biomedical Sciences, University of Western Australia

Centre for Microscopy, Characterisation and Analysis, the University of Western Australia

This story was contributed by the University of Western Australia. For more information, contact Dr Vanessa Fear or Diana Patalwala.

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