hyperpolarized 129xe mri for the assessment of bos with late onset lonipc

Conditions: Bronchiolitis Obliterans

Summary: the development of bronchiolitis obliterans syndrome (bos) and other late onset non-infectious pulmonary complications (lonipcs) following hematopoietic stem cell transplantation (hsct) is associated with a significantly worse prognosis, high disease burden, and excessive health resource utilization. in this proposal, the investigators plan to examine and compare different diagnostic modalities which can provide detailed physiological and anatomical characterization of lonipcs.

there is mounting evidence suggesting that current practice is failing to provide early detection of lonipcs, before critical loss of lung function occurs. furthermore, autopsy series in hsct patients have revealed a wide spectrum of pulmonary pathology in different compartments of the lung (airway, parenchyma, interstitium) within the same individual. these findings imply that lonipcs and the extent of their pulmonary involvement are under-recognized, which adversely impacts the clinical trajectory and outcomes of hsct patients. these findings also suggest that the underlying pathophysiology is multi-faceted and diffuse, highlighting a need for a multi-modal approach to early detection, and better characterization of the spectrum of pulmonary involvement. in this study, we plan to examine and compare different diagnostic modalities which can provide detailed physiological and anatomical characterization of lonipcs. we propose an observational study using hyperpolarized magnetic resonance imaging (mri) to capture the anatomical and functional spectrum of lonipcs post-hsct. hyperpolarized magnetic resonance imaging (mri) is a novel and noninvasive functional imaging method, with the capacity to evaluate pulmonary structure and function. inhaled hyperpolarized gas (129xenon) maps focal areas of ventilation defects, a functional consequence of small airway obstruction, which often goes undetected on pft in early disease states. it can provide additional information on alveolar structure and gas diffusion, lending insight into pathology in other compartments. oscillometry technique (fot) is a non-invasive technique using wave frequency to map out large and small airways, commonly used in pediatric pulmonology. we propose to examine the 2 novel modalities in hsct patients with and without lonipc/bos. we hypothesize that the use of functional-structural imaging and fot will provide better characterization and the extent of lonipcs in early diseases states post-hsct. these findings will provide invaluable insight into the pathophysiology of lonipcs, providing a platform for future research into the early diagnosis and treatment of these high-burden diseases.

Eligibility criteria:
inclusion criteria: * for participants who have known lonipc at enrollment (cross-sectional group): * patient is 18 - 70 years old * patient has received an allogenic hsct * diagnosed lonipc for participants who have no known lonipc, but are at risk by virtue of recently-diagnosed cgvhd: * patient is 18 - 70 years old * patient has received an allogenic hsct in the last 24 months * patient has a new diagnosis of cgvhd within the last 6 months by criteria of: * moderate- or severe- cgvhd as per nih consensus criteria, determined by a treating hematologist or * cgvhd requiring immunosuppression with prednisone at a dose of \> 0.5mg/kg/day, or alternate steroid-sparing agent exclusion criteria: * for participants who have known lonipc at enrollment (cross-sectional group): * age less than 18 years or greater than 70 years of age * current smoker (quit in the last 3 months) * smoking history greater than 20 pack years * presence of contraindications to pulmonary function testing including myocardial infarction within the last one month, hemoptysis, active communicable disease (e.g. tb), inability to follow commands, thoracic/abdominal/eye surgery within the last 3 months, pneumothorax, uncontrolled hypertension (sbp \> 180, dbp \> 110) or pulmonary embolism, other contraindication as determined by technical staff. * pregnancy prior to or during study * in the opinion of the investigator, subject is mentally or legally incapacitated, preventing informed consent from being obtained, or cannot read or understand the written material * patient has an implanted mechanically, electrically or magnetically activated device or any metal in their body which cannot be removed, including but not limited to pacemakers, neurostimulators, biostimulators, implanted insulin pumps, aneurysm clips, bio-prosthesis, artificial limb, metallic fragment or foreign body, shunt, surgical staples (including clips or metallic sutures and/or ear implants) (at the discretion of the mri technologist/3t manager) * in the investigator's opinion, subject suffers from any physical, psychological or other condition(s) that might prevent performance of the mri, such as severe claustrophobia for participants who have no known lonipc, but are at risk by virtue of recently-diagnosed cgvhd: * age less than 18 years or greater than 70 years of age * known history of late onset non-infectious pulmonary complication (lonipc) related to hsct * current smoker (quit in the last 3 months) * smoking history greater than 20 pack years * presence of contraindications to pulmonary function testing including myocardial infarction within the last one month, hemoptysis, active communicable disease (e.g. tb), inability to follow commands, thoracic/abdominal/eye surgery within the last 3 months, pneumothorax, uncontrolled hypertension (sbp \> 180, dbp \> 110) or pulmonary embolism, other contraindication as determined by technical staff. * pregnancy prior to or during study * in the opinion of the investigator, subject is mentally or legally incapacitated, preventing informed consent from being obtained, or cannot read or understand the written material * patient has an implanted mechanically, electrically or magnetically activated device or any metal in their body which cannot be removed, including but not limited to pacemakers, neurostimulators, biostimulators, implanted insulin pumps, aneurysm clips, bio-prosthesis, artificial limb, metallic fragment or foreign body, shunt, surgical staples (including clips or metallic sutures and/or ear implants) (at the discretion of the mri technologist/3t manager) * in the investigator's opinion, subject suffers from any physical, psychological or other condition(s) that might prevent performance of the mri, such as severe claustrophobia