Rendon C. Nelson MD, Presenter: Consultant, General Electric Company Consultant, Nemoto Kyorindo Co, Ltd Consultant, VoxelMetrix, LLC Research support, Bracco Group Research support, Becton, Dickinson and Company Speakers Bureau, Siemens AG Royalties, Wolters Kluwer nv

Kohkan Shamsi MD, PhD, Abstract Co-Author: Research Consultant, CMC Contrast AB

To determine the qualitative and quantitative efficacy of orally-administered manganese chloride tetrahydrate (CMC-001) for the evaluation of focal liver lesions (FLL) by MRI.

Unenhanced alone and combined unenhanced and CMC-001 enhanced T1- and T2-weighted images at 1.5T of 30 healthy volunteers and 134 patients included in five Phase I and II trials or for compassionate use were evaluated separately by one independent reader who was blinded to patient information, contrast agent dose and clinical diagnosis. Region-of-interest signal intensity (SI) measurements were acquired from the non-tumorous liver parenchyma, common bile duct (CBD), portal vein (PV), paraspinous muscle and FLL, when present. FLL were also scored for visualization, delineation, detection confidence and characterization. Mean signal intensity measurements and lesion contrast-to-noise ratios (CNR) were compared between pre- and post-contrast images. The detection of benign and malignant-appearing lesions were compared between unenhanced alone and combined unenhanced and CMC-001 enhanced images.

178 unenhanced and CMC-001 enhanced image pairs were available for evaluation (some patients were imaged more than once). Comparing T1-weighted unenhanced to enhanced images, there was a significant increase in the SI of both liver parenchyma and CBD (37% and 412%, respectively; p<.0004). There was also a statistically significant improvement in the lesion-to-liver CNR after CMC-001 administration (median: pre: 4.22, post: 12.12; p<.0001). Compared to unenhanced images alone, the combination of unenhanced and CMC-001enhanced images demonstrated 13% more malignant-appearing lesions. Also for malignant-appearing lesions, confidence in lesion localization in the "high" category increased from 41% to 56% (p<.0001), while confidence in lesion visualization and delineation in the "excellent" category increased from 32% to 44% (p<.0001) and from 18% to 36% (p<.0001), respectively.

This initial analysis shows that orally-administered manganese chloride tetrahydrate provides qualitative and quantitative improvement over unenhanced MRI for visualization and detection of focal liver lesions.

Manganese chloride tetrahydrate could be an alternative contrast agent for patients with known or suspected focal liver lesions in whom gadolinium-based contrast agents are contraindicated, particularly in patients with renal insufficiency.

Nelson, R, Shamsi, K, Evaluation of a New Manganese-based Orally-Administered Hepatobiliary MR Contrast Agent.  Radiological Society of North America 2014 Scientific Assembly and Annual Meeting, - ,Chicago IL. http://archive.rsna.org/2014/14005662.html