Contrast-enhanced magnetic resonance imaging (MRI) is the cornerstone for brain tumor diagnosis and
treatment planning. While its sensitivity for metastases is superior to that of CT or PET-CT, small lesions (<5-
mm) and leptomeningeal spread may still be missed, which can have a major impact on prognosis and
planning for stereotactic radiosurgery, as well as on the use of targeted biologics that cross the blood-brain
barrier. A method that could further improve the sensitivity and specificity of MRI for brain tumors would be of
great clinical benefit. Towards this end, we have developed a new class of pulse sequences, called T1
Relaxation-Enhanced Steady-State (T1RESS), that greatly improves the visibility of tumors in contrast-
enhanced MRI. Compared with existing neuroimaging techniques, T1RESS at least doubles the tumor-to-
background contrast while significantly improving the tumor-to-background contrast-to-noise ratio. An
“unbalanced” version (uT1RESS) renders blood vessel dark and is the focus of our proposal.
In a preliminary study of 54 adult patients that was published in Science Advances, uT1RESS provided
a remarkable twofold or greater improvement in tumor-to-brain contrast along with a marked improvement in
lesion-to-brain contrast-to-noise in comparison to standard-of-care MPRAGE and other pulse sequences that
are commonly used to image brain tumors. We found that even small metastatic tumor deposits and
leptomeningeal lesions that were difficult to distinguish from small blood vessels with standard imaging
techniques could be unambiguously identified.
The primary hypothesis of this two-year grant proposal is that R21 grant proposal is that the twofold or
greater improvement in sensitivity to gadolinium enhancement provided by uT1RESS will enable a
corresponding twofold reduction in GBCA dose, with non-inferior diagnostic accuracy compared to full dose
MRI using standard neuroimaging techniques. Studies of phantoms, healthy volunteers, and patients with
brain tumors along with Bloch equation modeling will be used to guide sequence optimization. Our specific
aims are as follows:
1. To maximize the sensitivity of uT1RESS to gadolinium enhancement while optimizing image quality
and minimizing scan time.
2. To perform a single site research trial at 3 Tesla to determine whether half dose contrast-enhanced MRI
using uT1RESS is non-inferior to full dose contrast-enhanced MRI using a standard neuroimaging technique in
patients with brain tumors.
