Study design for APT imaging of the mice lung using the small animal ventilator.

<p>The animal was mechanically ventilated for constant amplitude and frequency of respiration at 32 breaths/min in which inhalation and end-expiration was 0.2 s and 1.6 s, respectively. The lung was inflated until the intrapulmonary pressure becomes 20 cm H₂O. Fast spin-echo images were obtained following a presaturation pulse (continuous-wave block pulse, B1 = 1.7 µT, duration = 4 s) in the end-expiratory phase.</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

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

Modulation of CEST Images <i>in Vivo</i> by <i>T</i>₁ Relaxation: A New Approach in the Design of Responsive PARACEST Agents

A novel approach for the design of responsive paramagnetic chemical exchange saturation transfer (PARACEST) magnetic resonance imaging (MRI) agents has been developed where the signal is “turned on” by altering the longitudinal relaxation time (<i>T</i>₁) of bulk water protons. To demonstrate this approach, a model Eu­(DOTA-tetraamide) complex (DOTA = 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) containing two nitroxide free radical units was synthesized. The nitroxide groups substantially shortened the <i>T</i>₁ of the bulk water protons which, in turn, resulted in quenching of the CEST signal. Reduction of paramagnetic nitroxide moieties to a diamagnetic species resulted in the appearance of CEST. The modulation of CEST by <i>T</i>₁ relaxation provides a new platform for designing biologically responsive MRI agents

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