Identifying Recurrent Malignant Glioma after Treatment Using Amide Proton Transfer-Weighted MR Imaging: A Validation Study with Image-Guided Stereotactic Biopsy

Abstract

Purpose: To quantify the accuracy of amide proton transfer-weighted (APTw) MRI for identifying active glioma after treatment via radiographically guided stereotactic tissue validation.Experimental Design: Twenty-one patients who were referred for surgery for MRI features concerning for tumor progression versus treatment effect underwent preoperative APTw imaging. Stereotactic biopsy samples were taken from regions of interest with varying APTw signal intensities. The relationship between final clinical pathology and the histopathology of each of the 64 specimens was analyzed relative to APTw results. Analysis of confirmed recurrent tumor or treatment effect tissue was used to perform ROC analysis.Results: Eighteen of 21 patients had recurrent tumor, and 3 had treatment effect on clinical pathology. In 12 patients, there were multiple histopathologic assignments confirmed within the same tumor. Of the 64 total specimens, 20 specimens were active glioma, 27 mixed active and quiescent glioma, and 17 quiescent/no identifiable tumor. APTw signal intensity and histopathologic assignment, cellularity, and proliferation index had significant positive correlations (R ¼ 0.651, 0.580, and 0.458, respectively; all P < 0.001). ROC analysis with a 1.79% APTw intensity cutoff differentiated active from nonactive tumor (AUC of 0.881) with 85.1% sensitivity and 94.1% specificity. Analysis of clinical pathology showed the mean APTw intensity for each patient had 94.4% sensitivity and 100% positive predictive value for identifying recurrent glioma at this cutoff.Conclusions: APTw imaging hyperintensity may be a marker of active malignant glioma. It is able to distinguish between regions of heterogeneous abnormality on anatomic brain MRI with high sensitivity and specificity. Analysis and interpretation of data (e.g., statistical analysis, biostatistics, computational analysis):

APT‐weighted MRI: Techniques, current neuro applications, and challenging issues

“…) that true progression was associated with APTw hyperintensity, while pseudoprogression was associated with APTw isointensity to mild hyperintensity. A recent radiographically guided stereotactic biopsy study showed that APTw signal intensities were significantly higher in regions that represented active tumor than in regions that represented nonactive tumor, and that these two groups could be separated with an 85.1% sensitivity and a 94.1% specificity . This further supports the hypothesis that the APTw hyperintensity for active glioma can be used as a surrogate biomarker to differentiate recurrent tumor from treatment effects.…”

“…Several clinical studies have now confirmed the ability of APTw imaging to differentiate recurrent tumor from treatment effects . These early results demonstrate the potential of APTw imaging in neuro‐oncology, providing a noninvasive imaging biomarker for distinguishing active tumor from radiation necrosis.…”

“…Figures show some examples of these parameters in a human study at 3 T, confirming the minimizing of normal tissue and edema signal into the background and a strong tumor contrast. These saturation parameters were also used in the validation studies with APTw MRI‐directed biopsies . For other applications, the optimal parameters and analysis approaches are still under development.…”

“…Because of the presence of these multiple contributions, APT images defined by MTR asym (3.5 ppm) should be called APTw images. 13 It has been demonstrated theoretically [20][21][22] and with image-directed biopsies 23,24 that MTR asym (3.5 ppm) or APTw is a valid metric for imaging of brain tumors, which was the basis of the first commercial APTw imaging sequence on 3 T clinical MRI scanners. 25 To quantify more pure APT and NOE signals in vivo, several alternative data processing approaches 21,22,[26][27][28][29][30][31] have been proposed.…”

Fast 3D chemical exchange saturation transfer imaging with variably‐accelerated sensitivity encoding (vSENSE)

“…The CEST method can enhance the detection sensitivity of low‐concentration metabolites in vivo when repeated saturation transfer allows for an accumulation and amplification of the MRI signals derived from metabolite‐specific solute pools. Biomolecules that are detectable by various CEST techniques include polypeptides using amide proton transfer (APT), glycogen with “glycoCEST,” glycosaminoglycan by “gagCEST,” glutamate by “GluCEST,” glucose by “glucoCEST,” and creatine by “CrCEST.” Indeed, CEST MRI has been applied in patients with brain tumors, prostate cancer, breast cancer, and stroke using APT, osteoarthritis using gagCEST, epilepsy using GluCEST, and brain tumors using glucoCEST . Despite its great promise, the clinical use of CEST MRI is limited by the long acquisition times needed to acquire multiple frames at different saturation offset frequencies, and for quantification …”