Lung transplantation is a therapy for many patients with end-stage lung diseases. Unfortunately, studies report that most transplant recipients die from rejection. Rejection occurs because the lung transplant recipient’s body perceives the donor’s lungs as foreign and rejects the transplanted lungs. Many now believe that a series of small rejections lead to terminal failure of the transplanted lungs. The supply of lungs for transplant is the biggest bottleneck to perform a lung transplant, and many patients die while waiting. Therefore, it is critical to detect rejection early and treat it aggressively so that already-transplanted lungs can give the longest possible survival benefit to the recipients. Some lung transplant centers (like UVA Health) perform routine invasive lung sampling procedures called a bronchoscopy, pulmonary function test, and clinical exam to diagnose rejection. Lung sampling is typically performed in the right middle or left upper part of the lung because those areas are easy and convenient to sample. Unfortunately, many patients develop rejection unpredictably, after lung samplings showing normal results. The failure to effectively diagnose the rejection by bronchoscopy raises questions. Are clinicians sampling correct parts of the lung to diagnose rejection, and can we improve our lung sampling techniques?
 
A specialized MRI technique called hyperpolarized gas MRI (HGMRI) has been used to visualize and detect specific parts of the lung with abnormalities. Research by Drs Shim and Mata now indicates that the rejection happens in moth-eaten-like random patterns with normal and abnormal lung tissues alternating. These results suggest that the current way of sampling the right middle or left upper lung by bronchoscopy may be severely flawed.
 
In their iTHRIV pilot project, the researchers studied lung transplant patients who were scheduled to undergo surveillance bronchoscopy to detect rejection. The researchers first found the part of the patients' lung with rejection-like changes by HGMRI, then sampled the lung in two places, one normal and one abnormal area of the lung. These two areas of the lung from the same patient were compared to determine if abnormal findings in HGMRI correlate with rejection.

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In part 1 of this pilot project, 12 patients were imaged using HGMRI. As hypothesized, HGMRI was able to differentiate focal regions in the transplanted lungs that are abnormal and not performing well. The researchers developed an imaging tool that fuses the HGMRI images with the CT scan and produces a detailed 3D “path map” for the bronchoscopy, from the trachea all the way to the focal lung abnormality. With this imaging analysis tool, the researchers can provide 3D guidance ahead of the bronchoscopy procedure, helping in a novel and unparalleled way the planning of the bronchoscopy procedure. In part 2 of the project, the researchers were able to sample the abnormally functioning regions of the allografts (transplanted lung) with an unmatched planning and precision. The researchers also have been able to determine normal functioning regions of the allografts for comparison. The results were impactful. In several participants, the researchers were able to correlate initial allograft rejection from the standard clinical pathology samples with the abnormal HGMRI ventilation and gas exchange imaging. This new pre-bronchoscopy personalized planning developed for this project is already having a tremendous impact in how clinicians perform their bronchoscopies post transplantation. It is also helping the patients receive a more precise, potentially earlier diagnosis and earlier modified treatment plan in case of abnormal lung function or signs of early lung rejection. 

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To learn more about the exciting ongoing work of this team, see the article in UVA Medicine in Motion: Scientists Earn $7.4 Million for Lung Research Using Hyperpolarized Xenon MRI - Research - Medicine in Motion News