In this work we demonstrate that specific MR image contrast can be produced in the water signal that reflects endogenous cellular protein and peptide content in intracranial rat 9L gliosarcomas. Although the concentration of these mobile proteins and peptides is only in the millimolar range, a detection sensitivity of several percent on the water signal (molar concentration) was achieved. This was accomplished with detection sensitivity enhancement by selective radiofrequency (RF) labeling of the amide protons, and by utilizing the effective transfer of this label to water via hydrogen exchange. Brain tumors were also assessed by conventional T₁‐weighted, T₂‐weighted, and diffusion‐weighted imaging. Whereas these commonly‐used approaches yielded heterogeneous images, the new amide proton transfer (APT) technique showed a single well‐defined region of hyperintensity that was assigned to brain tumor tissue. Magn Reson Med 50:1120–1126, 2003.

A major problem in the clinical management of patients with brain tumors is distinguishing tumor recurrence from radiation-induced necrosis after brain tumor therapy. Zhou et al. use an MRI technique called amide proton transfer imaging to noninvasively differentiate between these two pathologies. The approach is successfully evaluated by comparing two orthotopic glioma models with a radiation necrosis model in rats. It remains difficult to distinguish tumor recurrence from radiation necrosis after brain tumor therapy. Here we show that these lesions can be distinguished using the amide proton transfer (APT) magnetic resonance imaging (MRI) signals of endogenous cellular proteins and peptides as an imaging biomarker. When comparing two models of orthotopic glioma (SF188/V+ glioma and 9L gliosarcoma) with a model of radiation necrosis in rats, we could clearly differentiate viable glioma (hyperintense) from radiation necrosis (hypointense to isointense) by APT MRI. When we irradiated rats with U87MG gliomas, the APT signals in the irradiated tumors had decreased substantially by 3 d and 6 d after radiation. The amide protons that can be detected by APT provide a unique and noninvasive MRI biomarker for distinguishing viable malignancy from radiation necrosis and predicting tumor response to therapy.

Amide proton transfer (APT) imaging is a technique in which the nuclear magnetization of water‐exchangeable amide protons of endogenous mobile proteins and peptides in tissue is saturated, resulting in a signal intensity decrease of the free water. In this work, the first human APT data were acquired from 10 patients with brain tumors on a 3T whole‐body clinical scanner and compared with T₁‐ (T₁w) and T₂‐weighted (T₂w), fluid‐attenuated inversion recovery (FLAIR), and diffusion images (fractional anisotropy (FA) and apparent diffusion coefficient (ADC)). The APT‐weighted images provided good contrast between tumor and edema. The effect of APT was enhanced by an approximate 4% change in the water signal intensity in tumor regions compared to edema and normal‐appearing white matter (NAWM). These preliminary data from patients with brain tumors show that the APT is a unique contrast that can provide complementary information to standard clinical MRI measures. Magn Reson Med, 2006.

Amide proton transfer (APT) imaging is a type of chemical exchange–dependent saturation transfer (CEST) magnetic resonance imaging (MRI) in which amide protons of endogenous mobile proteins and peptides in tissue are detected. Initial studies have shown promising results for distinguishing tumor from surrounding brain in patients, but these data were hampered by magnetic field inhomogeneity and a low signal‐to‐noise ratio (SNR). Here a practical six‐offset APT data acquisition scheme is presented that, together with a separately acquired CEST spectrum, can provide B₀‐inhomogeneity corrected human brain APT images of sufficient SNR within a clinically relevant time frame. Data from nine brain tumor patients at 3T shows that APT intensities were significantly higher in the tumor core, as assigned by gadolinium‐enhancement, than in contralateral normal‐appearing white matter (CNAWM) in patients with high‐grade tumors. Conversely, APT intensities in tumor were indistinguishable from CNAWM in patients with low‐grade tumors. In high‐grade tumors, regions of increased APT extended outside of the core into peripheral zones, indicating the potential of this technique for more accurate delineation of the heterogeneous areas of brain cancers. Magn Reson Med 60:842–849, 2008.