Guang Jia PhD, Presenter: Nothing to Disclose

Christina Louise Sammet PhD, Abstract Co-Author: Nothing to Disclose

Wenbo Wei, Abstract Co-Author: Nothing to Disclose

Jochen Keupp PhD, Abstract Co-Author: Employee, Koninklijke Philips Electronics NV

Huyen Thanh Nguyen MS, Abstract Co-Author: Nothing to Disclose

Michael Vinzenz Knopp MD, PhD, Abstract Co-Author: Nothing to Disclose

Jinyuan Zhou PhD, Abstract Co-Author: Nothing to Disclose

Amide proton transfer (APT) MRI has been emerging as a novel protein-based molecular imaging technique using endogenous contrast for oncologic imaging. We advanced this methodology to a clinically applicable approach and assessed its feasibility for quantitative assessment in different oncologic tumors.

A total of 20 patients were prospectively enrolled in a Phase I trial for assessment of the following primary malignancies in the pelvis, lung, liver, pancreas, and eye. All patients were imaged on a 3 Tesla MR system (Achieva, Philips Healthcare). A T1-weighted high-resolution three-dimensional isotropic volume examination (THRIVE) sequence was used in APT-MRI in order to provide high image resolution and SNR within the FDA SAR limit. Breath-hold THRIVE sequence was used for lung or abdomen cancer patients (16 seconds per breath hold). APT-MRI was acquired with saturation pre-pulse at 6 frequency offsets (5.8, 3.5, 1.2, -1.2, -3.5, and -5.8 ppm). The B0 field map was acquired using a dual-echo FFE sequence. The magnetization transfer ratio (MTR) asymmetry at ± 3.5 ppm, MTRasym(3.5ppm), was calculated with B0 correction for creating APT-MRI signal maps with the overlays and regions of interest.

The newly developed three-dimensional protocol revealed improved delineation of tumors at the protein level on APT-MR images assessed by blinded reviews. The measured MTRasym(3.5ppm) values were 4.0% ± 2.0% in bladder tumor regions, 4.5% ± 4.9% in prostate tumor regions, 2.1% ± 1.4% in orbital tumors, 12.4 ± 2.9% in liver metastasis regions, 6.1% ± 6.3% in pancreatic tumors, and 9.5% ± 4.9% in lung tumors. The MRI detectable mobile protein levels defined by MTRasym(3.5ppm) were significantly higher in the malignant regions than in their corresponding benign regions (P = 0.01).

The APT-MRI signal-based detection and quantification of endogenous cellular protein concentrations was shown to be a promising marker to improve tumor characterization as well as visualization. Malignant lesions consistently reveal higher signals due to their increased cellular content of mobile proteins. Dedicated Phase II trials to appropriately assess the efficacy of this approach should be undertaken.

The capability of the APT-MRI approach to detect characteristics of malignancy has the potential for improved imaging-based cancer management for clinical diagnosis and therapy assessment.

Jia, G, Sammet, C, Wei, W, Keupp, J, Nguyen, H, Knopp, M, Zhou, J, Advancing Tumor Molecular Diagnostics Using a New Protein-based Imaging Technique: Amide Proton Transfer MRI.  Radiological Society of North America 2011 Scientific Assembly and Annual Meeting, November 26 - December 2, 2011 ,Chicago IL. http://archive.rsna.org/2011/11007126.html