Amide Proton Transfer Imaging of Diffuse Gliomas: Effect of Saturation Pulse Length in Parallel Transmission-Based Technique

<div><p>In this study, we evaluated the dependence of saturation pulse length on APT imaging of diffuse gliomas using a parallel transmission-based technique. Twenty-two patients with diffuse gliomas (9 low-grade gliomas, LGGs, and 13 high-grade gliomas, HGGs) were included in the study. APT imaging was conducted at 3T with a 2-channel parallel transmission scheme using three different saturation pulse lengths (0.5 s, 1.0 s, 2.0 s). The 2D fast spin-echo sequence was used for imaging. Z-spectrum was obtained at 25 frequency offsets from -6 to +6 ppm (step 0.5 ppm). A point-by-point B0 correction was performed with a B0 map. Magnetization transfer ratio (MTR_asym) and ΔMTR_asym (contrast between tumor and normal white matter) at 3.5 ppm were compared among different saturation lengths. A significant increase in MTR_asym (3.5 ppm) of HGG was found when the length of saturation pulse became longer (3.09 ± 0.54% at 0.5 s, 3.83 ± 0.67% at 1 s, 4.12 ± 0.97% at 2 s), but MTR_asym (3.5 ppm) was not different among the saturation lengths in LGG. ΔMTR_asym (3.5 ppm) increased with the length of saturation pulse in both LGG (0.48 ± 0.56% at 0.5 s, 1.28 ± 0.56% at 1 s, 1.88 ± 0.56% at 2 s and HGG (1.72 ± 0.54% at 0.5 s, 2.90 ± 0.49% at 1 s, 3.83 ± 0.88% at 2 s). In both LGG and HGG, APT-weighted contrast was enhanced with the use of longer saturation pulses.</p></div

Amide Proton Transfer Imaging of Diffuse Gliomas: Effect of Saturation Pulse Length in Parallel Transmission-Based Technique - Fig 1

<p>Z-spectra of LGG <b>(A)</b>, HGG <b>(C)</b>, and corresponding NAWM <b>(B, D)</b>. Z-spectra of tumor was steeper than that of NAWM, presumably because of less MT effect in tumor compared with NAWM. Prolongation of saturation pulses results in larger MT effect and thus wider Z-spectra in both tumor and NAWM.</p

A case of glioblastoma multiforme (Grade IV, HGG).

<p>The APT-weighted signal of the tumor in the left temporal lobe is increased with the saturation length, and the contrast between tumor and normal brain tissue becomes larger at longer saturation pulses.</p

Analyses for Z-spectrum and MTR_asym of both types of lung tumors.

<p>Z-spectra of A549 (<b>A</b>) and LLC (<b>B</b>) tumors compared to that of spinal cord as a reference show that the LLC tumor has a larger CEST effect than A549 tumor. Corrected MTR_asym spectra of A549 and LLC (<b>C</b>) and corrected MTR_asym at 3.5 ppm (<b>D</b>) show that LLC has a larger APT effect than A549, which may be related to the malignancy of the tumors. *, <i>P</i>≤0.05; **, P≤0.01; ***, P≤0.001 by Student’s t-test.</p

Amide Proton Transfer Imaging of Diffuse Gliomas: Effect of Saturation Pulse Length in Parallel Transmission-Based Technique - Fig 2

<p>MTR_asym of tumor <b>(A)</b> and NAWM <b>(B)</b> and ΔMTR_asym <b>(C)</b> in LGG. MTR_asym (<b>A</b>) of tumor was decreased with the saturation length in lower frequency range (1–2 ppm), but equivalent at 3.5 ppm. MTR_asym of NAWM (<b>B</b>) is decreased with the saturation length in the entire frequency range. ΔMTR_asym (<b>C</b>) was increased with the saturation length at higher frequency offsets (>2 ppm).</p

A case of diffuse astrocytoma (Grade II, LGG).

<p>The APT-weighted signal of the tumor in the left frontal lobe is almost comparable in all the saturation pulse lengths, but the contrast between tumor and normal brain tissue is slightly increased at longer saturation pulses due to decreased signal in NAWM.</p

In-vivo APT imaging of lung tumors in the orthotopic mouse model.

<p>Representative T2-weighted images (left) and APT-weighted images (right, MTR_asym map at 3.5 ppm) of A549 (<b>A</b>) and LLC (<b>B</b>) where the tumors (open arrows) are delineated brighter than the surrounding tissues including spinal cord (closed arrows) and skeletal muscles. A typical region of interest to measure signal intensity on a tumor is demonstrated (<b>B</b>).</p

MTR_asym of tumor and NAWM and ΔMTR_asym in HGG.

<p>MTR_asym of tumor <b>(A)</b> was decreased with the saturation length in lower frequency range (<2 ppm), but was increased at 3.5 ppm. MTR_asym of NAWM <b>(B)</b> was decreased with the saturation length in entire frequency range. ΔMTR_asym <b>(C)</b> was increased with the saturation length at higher frequency (>2 ppm). ΔMTR_asym (3.5 ppm) with the 2 s saturation reached maximum at around 3.5 ppm (specific frequency of amide protons).</p

Micrographs of the A549 tumor and LCC tumor.

<p>Hematoxylin-eosin staining (original magnification×400) demonstrates that LCC (<b>C</b>) have higher cell density and larger cell nuclei compared to A549 (<b>A</b>). Ki-67 staining (original magnification×200) reveals larger fraction of positive cells seen in LCC (<b>D</b>) than in A549 (<b>B</b>). This indicates the presence of a larger number of cells in active phases of the cell cycle (G₁, S, G₂, and mitosis) and thus the aggressive nature of LCC.</p

MTR_asym (3.5 ppm) and ΔMTR_asym (3.5 ppm) of LGG and HGG.

<p>No significant differences were observed in MTR_asym (3.5 ppm) among the three saturation lengths in LGG, while MTR_asym (3.5 ppm) with the 1 s and 2 s saturation was significantly higher than that with the 0.5 s saturation in HGG (<b>A</b>). ΔMTR_asym (3.5 ppm) with the 1 s and 2 s saturation length was significantly higher than that with the 0.5 s saturation in LGG, and ΔMTR_asym (3.5ppm) of HGG significantly increased with the saturation length (<b>B</b>). Both MTR_asym (3.5ppm) and ΔMTR_asym (3.5ppm) were significantly higher in HGG than in LGG at any saturation pulse lengths.</p