Specimen/Scan Protocols

The LTRC follows specific protocols for collection of specimens, CT scans, and data. Under previous contract periods (LTRC I and II), specimens were collected from COPD, ILD, and control participants via transplant procedures, lung volume reduction surgery (LVRS), and biopsies. The current contract period (LTRC III) aims to collect biopsy tissue only from prospective control participants.

Horizontal Tabs

Specimen Collection

Horizontal Tabs

Tissue Specimens

All fixed and frozen tissues that are obtained as part of the LTRC study are prepared according to the instructions given in the LTRC Manual of Procedures (MOP).

Ideally, 100 mg of tissue is collected per fixative. If there is not sufficient tissue for at least one 100 mg aliquot per fixative, sites will priotize a frozen preparation, followed by RNALater, followed by formalin. Note glutaraldehyde specimens and HOPE fixed specimens were discontinued for the LTRC II and LTRC III studies.

The LTRC investigators have set as a goal that the ischemic period for LTRC tissue will be no longer than 15 minutes for Video Assisted Thoracoscopic Lung Biopsy (VATS) and other biopsy specimens.

All tissue specimens will be sent to the Tissue Core Laboratory and stored as follows:

  • RNAIater tissue is aliquoted and stored at -20°C.
  • Flash (snap) frozen tissue is aliquoted and stored at -80°C.
Blood Specimens

Blood will be collected from each participant. Some of this blood will be sent to each clinical center's clinical laboratory for determination of specified laboratory values. The remaining blood will be sent to the Tissue Core Laboratory and aliquoted/stored as follows:

  • DNA tubes are stored at -80°C. Isolated DNA is stored at -20°C in 5 µg aliquots.
  • Serum and plasma samples are stored in 150 microliter aliquots at -80°C.
Scans

Role of the Radiology Core Laboratory

The LTRC Radiology Core Laboratory (RCL) will coordinate the collection of CT scans of lung that may be diagnostic of fibrotic and non-fibrotic lung disease.

The role of the RCL is to:

  • Collect, quantitatively assess, and qualitatively assess CT scans sent to the RCL from the LTRC Clinical Centers
  • Transmit CT scans to the Data Coordinating Center for archival and distribution to qualified researchers
  • Transmit quantitative and qualitative CT scan data to the Coordinating Center

Role of the Data Coordinating Center

The DCC is the repository for all CT scans collected for the LTRC. They are responsible for maintaining records on CT scans sent to them by the RCL. These CT scans will be used in future, to-be-determined studies. The CT scans can be collected from the different sources which are described below.

The following types of CT scans are being collected as part of the LTRC:

Horizontal Tabs

LTRC Protocol CT Scan

The LTRC CT Scan is the preferred CT scan protocol to be collected for phenotyping the participant in the LTRC. The LTRC CT Scan is designed specifically to allow quantitative analysis of the lung as part of the LTRC project, and requires specific acquisition and reconstruction parameters that enable data to be as comparable as possible between the different participants. A subset of the CT scanners available at the clinical centers will be certified for use in obtaining this specific LTRC CT scan trial through an ongoing QA assessment and Protocol validation process. The precise parameters used for obtaining this LTRC CT dataset will be optimized for each specific CT scanner at a clinical center. Specifically, the full LTRC CT Scan Protocol will consist of helically acquired datasets on a multidetector CT scanner (with no less than 16 detectors) as well as scout/localization images as needed. Thin-slice images (1.0 mm or less) will be obtained and reconstructed at 50% overlap in both a high-resolution kernel (with specific accommodation for this kernel's density accuracy) and a kernel with lower noise and spatial frequency. These scans will be obtained in the supine position at full inspiration, supine and suspended full expiration and prone full inspiration. Scans will be optimized to allow for single breath acquisition in less than 10 seconds. Radiation dose will be adjusted for the participant's size. The ALARA (as low as reasonably allowable) principle will be utilized in these studies with accommodation for the adequate signal/noise ratio to realize the experimental quantitative analysis goals of the LTRC. The effective dose for the inspiratory phase LTRC CT Scan will be approximately 3-5 millisieverts (mSv), and a lower dose expiratory phase and prone series will each be approximately 2-3 mSv.

The images obtained from these scans will be sent to the Radiology Core Laboratory for analysis and storage as described below. Several scan protocols, based on different CT scanner brands and models, with appropriate weight-based dose adjustments and specific breathing instructions for participants and technologist information sheets are included in the LTRC Manual of Operations.

Historical CT Scan

A less desirable alternative to the LTRC CT Scan for participants enrolled in the LTRC that still fulfills the imaging requirements is a CT scan of the chest previously obtained for clinical reasons. These historical exams must have been obtained less than six months from the time of evaluation at the clinical center and must also be in digital DICOM format for transfer to the RCL. Volumetric high-resolution imaging (slice thickness less than 2mm) with a field of view sufficient to visualize the entire lung volume with non-contrast technique is preferred.  The CT portion of a PET/CT, imaging performed with intravenous contrast, image acquisition/reconstruction that is not volumetric (i.e. HRCT with gap) or slice thickness greater than 2mm is not preferred.  Subjects who do not have historical imaging with a preferred technique should be strongly encouraged to obtain the LTRC Protocol CT prior to surgery. Radiographs (chest x-ray) and other imaging modalities (MRI, V/Q scans, Ultrasound) are not acceptable. The participant must consent to use of a clinical scan for research purposes, its storage at the Mayo Clinic, or another repository designated by the NHLBI, and the sharing of results and de-identified image data with future researchers as part of the LTRC data repository. If more than one historical exam is available, the most recent examination with optimal acquisition and reconstruction parameters (non-contrast-enhanced, volumetric, high-resolution CT images with (thickness of 2mm or less) will be sent to the RCL for analysis and storage as described in the sections below. In order of preference, non-contrast exam, volumetric high-resolution technique and age of exam are to be considered.  For example, if a 1 week old enhanced pulmonary embolism protocol CT, a 1 month old PET/CT and a 3 month old non-contrast volumetric high-resolution CT are available, the 3-month old non-contrast high-resolution CT would be preferred). The LTRC Protocol CT acquired prospectively would be preferred to any of the historical exams, if that can be acquired prior to surgery.

Scan Images

The RCL makes available to the Data Coordinating Center (DCC) three representative images of the upper, middle, and lower lung. Each image will provide a view of the right and left lung.

The images have been digitized for incorporation into an image repository that can be accessed over the Internet by researchers. The researchers will not be allowed to view the patient's direct identifiers (name, address, etc.) In fact, no slide will be available to a researcher unless there are at least six patients with similar clinical parameters for the request being made.

The researcher will then be shown a random sample of all of the eligible CT scans with the specified parameters.

This procedure is being implemented to protect the confidentiality of the patient who volunteered to allow CT scan information to be collected for this very important study.