Precisely Targeting Gadolinium for MS Patients Who Truly Need It

2019 Imaging Innovation Award Winner: Reduction of Unnecessary Gadolinium-Based Contrast in Multiple Sclerosis Patients

By the Department of Radiology at the Hospital of the University of Pennsylvania

Patients with multiple sclerosis (MS) can receive more than 60 contrast-enhanced MRI exams during the course of their lifetime. Growing evidence suggests that there is deposition of free gadolinium in the brain and other organs with gadolinium-based contrast agents (GBCAs), even in patients with normal renal function. In fact, the FDA recently issued a warning on all GBCAs, although the clinical significance still remains unknown. We recently conducted a study showing that contrast enhancement of MS lesions is only seen in patients with new disease activity on noncontrast imaging (Mattay et al., “Do All Patients with Multiple Sclerosis Benefit from the Use of Contrast on Serial Follow-Up MR Imaging? A Retrospective Analysis,” American Journal of Neuroradiology, October 2018). This highlighted an opportunity to administer GBCAs only in MS patients who show evidence of new disease activity on noncontrast imaging, which represents only 25% or so of patients.

Aims and objectives. We sought to minimize GBCA use in MS follow-up patients by only giving contrast to patients who have evidence of new disease activity on noncontrast imaging. This form of precision diagnostics can prevent possible side effects related to GBCA use while also decreasing patient scan time, cost and discomfort. In addition, it may significantly reduce costs to the healthcare system by minimizing unnecessary imaging and increasing the possibility of scanning other patients who need imaging sooner. As part of this project, we trained 3D laboratory technologists to perform preliminary, real-time analysis of the T2/FLAIR noncontrast images using our in-house computer-assisted-detection (CAD) software. Therefore, a secondary aim was to train the technologists to perform this task with high accuracy.

Leadership and project management. Prior to implementing a new protocol, we held several multidisciplinary meetings to discuss how to exactly limit IV contrast in MS follow-up patients. Several meetings were first held within the radiology department, which included the department chair, the neuroradiology division chief, the neuroradiologists in charge of MRI protocols and the MS CAD software, as well as MRI technologists and the director of the 3D lab. After arriving at a general agreement to proceed within the department, we held several meetings between individual radiologists and MS neurologists, and we met with the MS neurology group during their weekly group meeting. Some neurologists expressed hesitancy to start this new protocol, but they and all stakeholders agreed to pilot the new workflow during a two-month period to determine actual real-world performance and assess benefits and disadvantages.

Key steps. We created a training module to help the 3D lab technologists learn the MS CAD software. The module incorporated multiple examples and explanations of typical true positives and false positives. The project team decided that patients who agreed to participate in this new protocol would not receive an IV prior to being placed in the MRI scanner. After the 3D FLAIR sequence was obtained following a localizer scan, the scanning MRI technologist would send the exam to PACS and let the 3D lab know it could be processed. The 3D lab technologist would then run the CAD software, which takes approximately 10 minutes to process an exam. The 3D lab technologist would review the output of the CAD software for the presence or absence of new lesions in the brain and let the MRI technologist know whether the patient needed contrast-enhanced imaging or not. If the patient needed contrast, it would be injected by the technologist. If no contrast was needed, the MR technologist would omit the post-contrast sequences of the brain and spine, which consisted of 15 minutes of additional sequences when the patient was ordered for imaging of the brain, cervical spine and thoracic spine.

During the first week of the pilot, a neuroradiologist reviewed each of the cases. After the first week, if the technologists felt unsure about any particular case, they had the option to call a neuroradiologist for their opinion of whether or not there were new lesions in the brain as shown by CAD and, thus, whether or not to inject contrast.

Positive outcomes. During the pilot period, 153 subjects were included in the new protocol. GBCA use in MS follow-up patients was reduced by 87%. As far as the secondary outcome of training 3D lab technologists to interpret the presence of new disease activity, the technologists’ overall accuracy was 94.8% with a sensitivity of 80.0% for detecting new lesions and a specificity of 97.0% to rule out the presence of new lesions.

Innovative elements. We led a multidisciplinary effort to improve the care of MS patients by targeting the use of contrast in follow-up scans. We incorporated our image analysis software into the clinical workflow to identify the patients who would most benefit from intravenous contrast administration in real time, based on whether the patient had new active disease on noncontrast imaging. We did this by developing a rapid communication scheme between the 3-D lab technologists who post-processed the images and the MRI technologists who scanned the patients. This allowed us to reach our goal of minimizing contrast use and unnecessary imaging while still accurately targeting contrast use for patients who needed it.


Submitted by Jeff Rudie, MD, PhD, a former Penn Medicine radiology resident who is now with UC-San Francisco.

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