Xenon imaging could detect lung involvement after HSCT

SALT LAKE CITY – Hyperpolarized xenon-129 magnetic resonance imaging, or ¹²⁹Xe MRI, showed strong promise for revealing early lung ventilation deficits in pediatric hematopoietic stem cell transplant (HSCT) patients in a proof-of-concept study.

The use of hyperpolarized xenon gas in this setting remains investigational, but is emerging as a safe non-ionizing approach for mapping and quantifying regional airway obstruction in the pediatric population. It has been shown to be more sensitive to early disease than the current clinical gold standard of measuring forced expiratory volume in 1 second (FEV₁) by spirometry, Laura L. Walkup, PhD, said at the combined annual meetings of the Center for International Blood & Marrow Transplant Research and the American Society for Blood and Marrow Transplantation.

The ¹²⁹Xe MRI provides regional information that spirometry cannot, allowing for a targeted approach to planned procedures such as bronchoscopy, said Dr. Walkup of Cincinnati Children’s Hospital Medical Center.

“We hypothesized that hyperpolarized ¹²⁹Xe MRI would be sensitive to lung abnormalities in the pediatric HSCT population,” she said.

Of 13 patients aged 6-13 years (mean, 10 years) who were enrolled in the study and underwent ¹²⁹XeMRI, 9 also completed spirometry successfully, and the average FEV₁ in those patients was 83% of the predicted value.

Ventilation deficits were apparent on the ¹²⁹Xe MRI imaging in 8 of the 13 subjects and varied in regional distribution. The whole-lung ¹²⁹Xe ventilation defect percentage for the HSCT group was 14%, which was significantly greater than the approximately 6% ventilation defect percentage in a cohort of age-matched controls, Dr. Walkup said, noting that ventilation deficits were seen in three of four subjects who were unable to complete reliable spirometry.

“So those are lung abnormalities that may have otherwise gone undetected,” she said, adding that hyperpolarized xenon gas also highlighted the wide individual variation in ventilation, even among cases with similar FEV₁ percentages.

The findings are notable, because pulmonary complications such as bronchiolitis obliterans are a major source of morbidity and mortality in the pediatric HSCT population, and an accurate and early diagnostic tool identifying the location and severity of suspected obstructive lung pathology following HSCT is desperately needed, she said.

The HSCT patients in the current study included four boys and nine girls. Isotopically-enriched xenon gas (86% ¹²⁹Xe) was hyperpolarized using a commercial polarizer and images were acquired during a breath hold of up to 16 seconds and up to 1 L of xenon gas. Conventional anatomic MR images also were acquired.

The ¹²⁹Xe ventilation was quantified using a less than 60% mean whole-lung ¹²⁹Xe signal threshold, and was compared to FEV₁ percentage predicted as measured via spirometry.

The procedure was well tolerated by all patients, Dr. Walkup said, noting that no patients withdrew from the study, and all were able to maintain the required breath hold.

Drops in blood oxygen saturation level did occur, but were transient and resolved within 10-30 seconds of normal breathing. Further, there were no changes in heart rate during imaging, and any side effects related to xenon, such as tingling in extremities, dizziness, or euphoria, were also quickly resolved with normal breathing, she said.

“There were no serious adverse events related to the study ... these results are in good agreement with previously published safety assessments of xenon in kids and in adults, and at our institution we routinely perform xenon imaging in children as young as age 6,” she added.

The findings, which are consistent with those seen in studies of other conditions such as cystic fibrosis, asthma, and chronic obstructive pulmonary disease, suggest that ¹²⁹Xe MRI is an emerging modality with strong translational potential for detecting early pulmonary involvement following HSCT, she said.

“The real power of the xenon MRI is the spatial information that it provides; we can use that information to plan targeted procedures like bronchoscopy and biopsies ... and since it is non-ionizing, it may be used serially to assess disease progression or response to an intervention,” Dr. Walkup said.

She noted, however, that because it is not yet approved by the Food and Drug Administration, and because it requires specialized expertise and hardware, it is available at only a handful of centers worldwide.

There is a long way to go before the technology will be widely clinically implemented, but work is ongoing at Cincinnati Children’s Hospital to determine how xenon MRI may play a role in pulmonary screening of patients, she said.

Dr. Walkup reported having no financial disclosures.

[email protected]

SOURCE: Walkup L et al. 2018 BMT Tandem Meetings Abstract 56.

SALT LAKE CITY – Hyperpolarized xenon-129 magnetic resonance imaging, or ¹²⁹Xe MRI, showed strong promise for revealing early lung ventilation deficits in pediatric hematopoietic stem cell transplant (HSCT) patients in a proof-of-concept study.

The use of hyperpolarized xenon gas in this setting remains investigational, but is emerging as a safe non-ionizing approach for mapping and quantifying regional airway obstruction in the pediatric population. It has been shown to be more sensitive to early disease than the current clinical gold standard of measuring forced expiratory volume in 1 second (FEV₁) by spirometry, Laura L. Walkup, PhD, said at the combined annual meetings of the Center for International Blood & Marrow Transplant Research and the American Society for Blood and Marrow Transplantation.

The ¹²⁹Xe MRI provides regional information that spirometry cannot, allowing for a targeted approach to planned procedures such as bronchoscopy, said Dr. Walkup of Cincinnati Children’s Hospital Medical Center.

“We hypothesized that hyperpolarized ¹²⁹Xe MRI would be sensitive to lung abnormalities in the pediatric HSCT population,” she said.

Of 13 patients aged 6-13 years (mean, 10 years) who were enrolled in the study and underwent ¹²⁹XeMRI, 9 also completed spirometry successfully, and the average FEV₁ in those patients was 83% of the predicted value.

Ventilation deficits were apparent on the ¹²⁹Xe MRI imaging in 8 of the 13 subjects and varied in regional distribution. The whole-lung ¹²⁹Xe ventilation defect percentage for the HSCT group was 14%, which was significantly greater than the approximately 6% ventilation defect percentage in a cohort of age-matched controls, Dr. Walkup said, noting that ventilation deficits were seen in three of four subjects who were unable to complete reliable spirometry.

“So those are lung abnormalities that may have otherwise gone undetected,” she said, adding that hyperpolarized xenon gas also highlighted the wide individual variation in ventilation, even among cases with similar FEV₁ percentages.

The findings are notable, because pulmonary complications such as bronchiolitis obliterans are a major source of morbidity and mortality in the pediatric HSCT population, and an accurate and early diagnostic tool identifying the location and severity of suspected obstructive lung pathology following HSCT is desperately needed, she said.

The HSCT patients in the current study included four boys and nine girls. Isotopically-enriched xenon gas (86% ¹²⁹Xe) was hyperpolarized using a commercial polarizer and images were acquired during a breath hold of up to 16 seconds and up to 1 L of xenon gas. Conventional anatomic MR images also were acquired.

The ¹²⁹Xe ventilation was quantified using a less than 60% mean whole-lung ¹²⁹Xe signal threshold, and was compared to FEV₁ percentage predicted as measured via spirometry.

The procedure was well tolerated by all patients, Dr. Walkup said, noting that no patients withdrew from the study, and all were able to maintain the required breath hold.

Drops in blood oxygen saturation level did occur, but were transient and resolved within 10-30 seconds of normal breathing. Further, there were no changes in heart rate during imaging, and any side effects related to xenon, such as tingling in extremities, dizziness, or euphoria, were also quickly resolved with normal breathing, she said.

“There were no serious adverse events related to the study ... these results are in good agreement with previously published safety assessments of xenon in kids and in adults, and at our institution we routinely perform xenon imaging in children as young as age 6,” she added.

The findings, which are consistent with those seen in studies of other conditions such as cystic fibrosis, asthma, and chronic obstructive pulmonary disease, suggest that ¹²⁹Xe MRI is an emerging modality with strong translational potential for detecting early pulmonary involvement following HSCT, she said.

“The real power of the xenon MRI is the spatial information that it provides; we can use that information to plan targeted procedures like bronchoscopy and biopsies ... and since it is non-ionizing, it may be used serially to assess disease progression or response to an intervention,” Dr. Walkup said.

She noted, however, that because it is not yet approved by the Food and Drug Administration, and because it requires specialized expertise and hardware, it is available at only a handful of centers worldwide.

There is a long way to go before the technology will be widely clinically implemented, but work is ongoing at Cincinnati Children’s Hospital to determine how xenon MRI may play a role in pulmonary screening of patients, she said.

Dr. Walkup reported having no financial disclosures.

[email protected]

SOURCE: Walkup L et al. 2018 BMT Tandem Meetings Abstract 56.

SALT LAKE CITY – Hyperpolarized xenon-129 magnetic resonance imaging, or ¹²⁹Xe MRI, showed strong promise for revealing early lung ventilation deficits in pediatric hematopoietic stem cell transplant (HSCT) patients in a proof-of-concept study.

The use of hyperpolarized xenon gas in this setting remains investigational, but is emerging as a safe non-ionizing approach for mapping and quantifying regional airway obstruction in the pediatric population. It has been shown to be more sensitive to early disease than the current clinical gold standard of measuring forced expiratory volume in 1 second (FEV₁) by spirometry, Laura L. Walkup, PhD, said at the combined annual meetings of the Center for International Blood & Marrow Transplant Research and the American Society for Blood and Marrow Transplantation.

The ¹²⁹Xe MRI provides regional information that spirometry cannot, allowing for a targeted approach to planned procedures such as bronchoscopy, said Dr. Walkup of Cincinnati Children’s Hospital Medical Center.

“We hypothesized that hyperpolarized ¹²⁹Xe MRI would be sensitive to lung abnormalities in the pediatric HSCT population,” she said.

Of 13 patients aged 6-13 years (mean, 10 years) who were enrolled in the study and underwent ¹²⁹XeMRI, 9 also completed spirometry successfully, and the average FEV₁ in those patients was 83% of the predicted value.

Ventilation deficits were apparent on the ¹²⁹Xe MRI imaging in 8 of the 13 subjects and varied in regional distribution. The whole-lung ¹²⁹Xe ventilation defect percentage for the HSCT group was 14%, which was significantly greater than the approximately 6% ventilation defect percentage in a cohort of age-matched controls, Dr. Walkup said, noting that ventilation deficits were seen in three of four subjects who were unable to complete reliable spirometry.

“So those are lung abnormalities that may have otherwise gone undetected,” she said, adding that hyperpolarized xenon gas also highlighted the wide individual variation in ventilation, even among cases with similar FEV₁ percentages.

The findings are notable, because pulmonary complications such as bronchiolitis obliterans are a major source of morbidity and mortality in the pediatric HSCT population, and an accurate and early diagnostic tool identifying the location and severity of suspected obstructive lung pathology following HSCT is desperately needed, she said.

The HSCT patients in the current study included four boys and nine girls. Isotopically-enriched xenon gas (86% ¹²⁹Xe) was hyperpolarized using a commercial polarizer and images were acquired during a breath hold of up to 16 seconds and up to 1 L of xenon gas. Conventional anatomic MR images also were acquired.

The ¹²⁹Xe ventilation was quantified using a less than 60% mean whole-lung ¹²⁹Xe signal threshold, and was compared to FEV₁ percentage predicted as measured via spirometry.

The procedure was well tolerated by all patients, Dr. Walkup said, noting that no patients withdrew from the study, and all were able to maintain the required breath hold.

Drops in blood oxygen saturation level did occur, but were transient and resolved within 10-30 seconds of normal breathing. Further, there were no changes in heart rate during imaging, and any side effects related to xenon, such as tingling in extremities, dizziness, or euphoria, were also quickly resolved with normal breathing, she said.

“There were no serious adverse events related to the study ... these results are in good agreement with previously published safety assessments of xenon in kids and in adults, and at our institution we routinely perform xenon imaging in children as young as age 6,” she added.

The findings, which are consistent with those seen in studies of other conditions such as cystic fibrosis, asthma, and chronic obstructive pulmonary disease, suggest that ¹²⁹Xe MRI is an emerging modality with strong translational potential for detecting early pulmonary involvement following HSCT, she said.

“The real power of the xenon MRI is the spatial information that it provides; we can use that information to plan targeted procedures like bronchoscopy and biopsies ... and since it is non-ionizing, it may be used serially to assess disease progression or response to an intervention,” Dr. Walkup said.

She noted, however, that because it is not yet approved by the Food and Drug Administration, and because it requires specialized expertise and hardware, it is available at only a handful of centers worldwide.

There is a long way to go before the technology will be widely clinically implemented, but work is ongoing at Cincinnati Children’s Hospital to determine how xenon MRI may play a role in pulmonary screening of patients, she said.

Dr. Walkup reported having no financial disclosures.

[email protected]

SOURCE: Walkup L et al. 2018 BMT Tandem Meetings Abstract 56.