MR imaging of high-grade brain tumors using endogenous protein and peptide-based contrast

Abstract

Amide proton transfer (APT) imaging is a novel MRI technique, in which the amide protons of endogenous proteins and peptides are irradiated to accomplish indirect detection using the bulk water signal. In this paper, the APT approach was added to a standard brain MRI protocol at 3T, and twelve patients with high-grade gliomas confirmed by histopathology were scanned. It is shown that all tumors, including one with minor gadolinium enhancement, showed heterogeneous hyperintensity on the APT images. The average APT signal intensities of the viable tumor cores were significantly higher than those of peritumoral edema and normal-appearing white matter (P<0.001). The average APT signal intensities were significantly lower in the necrotic regions than in the viable tumor cores (P=0.004). The APT signal intensities of the cystic cavities were similar to those of the viable tumor cores (P>0.2). The initial results show that APT imaging at the protein and peptide level may enhance non-invasive identification of tissue heterogeneity in high-grade brain tumors.

Fig. 1

Flow chart of APT imaging data processing. After raw data are loaded and organized, the procedure is divided into the generation of a B0 map and the correction of APT data using the B0 map.

Fig. 2

MR images for a patient with astrocytoma (grade III). (a) T2-weighted image shows a heterogeneously hyperintense focus in the right medial parietal lobe. (b) T1-weighted image shows that the entire tumor is hypointense. (c) Gadolinium-enhanced T1-weighted image demonstrates the typical imaging characteristics of a high-grade glioma: an enhancing tumor core (red arrow) with a non-enhancing necrotic area (pink arrow). (d) APT image shows that the tumor core (red arrow) is hyperintense, while the necrotic region (pink arrow) and edema area (orange arrow) have low APT signals. The blue strip (white arrow) adjacent to the surface of brain on the APT image may be the artifact caused by head motion.

Fig. 3

MR images from a patient with recurrent astrocytoma (grade III), acquired four months after treatment. (a) T2-weighted image shows the recurrence of glioma with heterogeneous hyperintensity in the left parietal lobe. (b) T1-weighted image shows a heterogeneously hypointense lesion. The exact location of the tumor core is not clear. (c) Post-contrast T1-weighted image reveals a gadolinium-enhancing tumor core (red arrow) and a necrotic area (pink arrow). The recurrent tumor is associated with the surrounding edema and mass effect. (d) APT image shows that there is a clear increase in APT signal intensity in the tumor core, identified by the gadolinium-enhanced T1-weighted image. The regions of necrosis (pink arrow) and edema (orange arrow) are almost isointense on APT.

Fig. 4

MR images for a patient with glioblastoma multiforme. (a) T2-weighted image demonstrates a large tumor of abnormal signals in the left frontal lobe. The area with cyst formation (black arrow) is clearly visible. (b) T1-weighted image shows that the entire tumor is hypointense. (c) Gadolinium-enhanced T1-weighted image demonstrates an enhancing tumor core (red arrow) with non-enhancing necrotic areas. (d) APT image shows that both the gadolinium-enhancing tumor core (red arrow) and the cystic cavity (black arrow) have high APT signal intensities, while the necrotic regions (pink arrow) and edema areas (orange arrow) have low APT signal intensities.

Fig. 5

MR images for a patient with glioblastoma multiforme. (a) FLAIR image shows a large tumor of heterogeneous signal intensities in the right frontal lobe. The hypointense region may represent hemorrhage. (b) T1-weighted image demonstrates that the entire tumor is mostly hypointense, with a small region of high signal intensities (red arrowhead) that is the characteristic of hemorrhage. (c) Gadolinium-enhanced T1-weighted image shows a slightly enhancing tumor core (red arrow) with a non-enhancing cystic cavity (black arrow) filled with liquid-like, chronic hemorrhage. (d) APT image shows that both the tumor core (red arrow) and the cystic cavity (black arrow) generally have high APT signals, while the clot (red arrowhead) has a low APT signal. The red spot (white arrow) near the ventricle on the APT image was an artifact. (e) H&E-stained brain section (×50) confirms the existence of high-density multi-form tumor cells in the tumor core (red arrow).

Fig. 6

Quantitative analysis of the APT images from all patients studied in this work. (a) Examples of the definition of the regions of interest. (b) Average APT intensities and corresponding 95% confidence intervals plotted as a function of tissue type. (I) viable tumor core; (II) necrosis; (III) cystic component; (IV) immediate edema; (V) peripheral edema; (VI) ipsilateral normal-appearing white matter; (VII) contralateral normal-appearing white matter. The APT intensity is the percentage of the bulk water signal.