Differentiating the treatment-related effect from tumor recurrence using amide proton transfer‐weighted (APTW) and pseudo-continuous arterial spin labeling (pcASL) MRI
Qihong Rui1, Dexia Kong1, Tianyu Zou1, Yingjie Mei2, Hao Yu1, Shanshan Jiang3, Xianlong Wang1, Jinyuan Zhou3, and Zhibo Wen1

1Department of Radiology, Zhujiang Hospital of Southern Medical University, Guangzhou, China, 2Philips Healthcare, Guangzhou, China, 3Division of MR Research, Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD, United States


Discriminating treatment-related effect from tumor recurrence with is critical for treatment decision-making. Amide proton transfer (APT) and pseudo-continuous arterial spin labeling (pcASL) are two non-invasive advanced magnetic resonance imaging (MRI) techniques. In this study we combined two techniques hoping to explore their diagnostic performance in differentiating treatment-related effect from tumor recurrence.


Maximal, safe resection, followed by radiation therapy and chemotherapy is typical treatment for patients with newly diagnosed high-grade gliomas1. This treatment strategy can lead to a treatment-related change which can appear as diverse patterns of a progressive, contrast-enhancing lesion on post-treatment MRI. Discriminating treatment-related effect from tumor recurrence with non-invasive method is challenging but critical for selecting the appropriate treatment strategy. APT MRI is a new endogenous molecular imaging technique based on chemical exchange-dependent saturation transfer (CEST) 2. Previous studies have demonstrated that APT MRI had the potential to distinguish viable malignancy versus radiation necrosis and predict tumor response to therapy3. The pcASL technique, a newly developed PWI sequence, has been explored in the evaluation of perfution of brain tumors4, 5. The purpose of this work was to investigate the diagnostic performance of APT and pcASL MRI for differentiating treatment-related effect from recurrence in patients with post-treatment high-grade gliomas.


This retrospective study was approved by the local ethics committee, and the requirement for informed consent was waived. Nineteen patients who underwent both APT and pcASL imaging studies for brain tumors on the basis of a clinical indication of suspected recurrence were assessed. All MR scans were performed on a clinical 3.0T scanner (Ingenia, Philips). APT imaging was implemented using a 3D TSE DIXON sequence6. 3D pcASL imaging was acquired by using a GraSE pulse sequence. APTW value and CBF (ml/min/100 g) was calculated automatically on console. The regions of interest (ROI) were manually circumscribed in APTW and CBF image around the largest cross-sectional area of the lesion, covering the whole area of abnormal intensity on the Gd-T1W image. The maximum, average APTW value (ie, mAPTW, aAPTW) and CBF(ie, mCBF, aCBF) of the lesion from all ROIs for each patient were recorded. The rAPTW value [aAPTW of the lesion minus the APTW value of contralateral normal-appearing white matter (CNAWM)] and CBF ratios(aCBF of the lesion divided by the CBF of CNAWM) were also assessed. aAPT, mAPT, aCBF, mCBF, rAPTW and normalized CBF ratios were compared between two groups using Student’s t test, or Mann-Whitney U test when not normally distributed. The diagnostic performance of the parameters was assessed with receiver operating characteristic (ROC) curve and area under curve (AUC).

Results and Discussion

All cases were confirmed by surgical diagnoses or clinical-radiologic follow-up in which 5 were treatment-related effect (Figure 1) and 14 were tumor recurrence (Figure 2). mAPTW, aAPTW, rAPTW, mCBF, aCBF and CBF ratio in lesions were significantly larger in the recurrence group than in the treatment-related effect group (p < 0.05). (Table 1) The mATPW showed the best performance for discriminating recurrence from treatment-related effect, followed by mCBF, aCBF, rAPTW, aAPTW, while CBF ratio showed the lowest diagnostic performance.


Our findings indicate that APTW and pcASL imaging are useful for assessing the state of high-grade gliomas after surgery followed by radiotherapy and chemotherapy. These two supplementary non-invasive methods showed the potential to improve the diagnostic performance in the identification between recurrence and treatment-related effect.


No acknowledgement found.


1.Stupp R, Mason WP, van den Bent MJ, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 2005;352:987–996.

2. Zhou J, Lal B, Wilson DA, Laterra J, van Zijl PC. Amide proton transfer (APT) contrast for imaging of brain tumors. Magn Reson Med 2003;50(6):1120‐1126.

3. Zhou J, Tryggestad E, Wen Z, et al. Differentiation between glioma and radiation necrosis using molecular magnetic resonance imaging of endogenous proteins and peptides. Nature Medicine 2011; 17: 130–134.

4. Lehmann P, Monet P, de Marco G, et al. A comparative study of perfusion measurement in brain tumours at 3 Tesla MR: arterial spin labeling versus dynamic susceptibility contrast-enhanced MRI. Eur Neurol 2010; 64: 21–26.

5. Järnum H, Steffensen EG, Knutsson L, et al. Perfusion MRI of brain tumours: a comparative study of pseudo-continuous arterial spin labeling and dynamic susceptibility contrast imaging. Neuroradiology 2010; 52: 307–317.

6.Jochen Keupp, Jinyuan Zhou, and Osamu Togao. 3D Clinical APTw MRI with Improved Contrast Homogeneity. #1506, 2016 ISMRM


Figure 1: A 43-year-old male with glioma sarcomatosum (WHOIV) in the right temporal lobe. T2WI demonstrated a mass in the right temporal lobe with edema, ring-like enhanced on the Gd‐T1W image. The CBF map showed the masses with hypoperfusion. APTW image showed the masses as a slightly hyperintense scattered patch.

Figure 2: A 58-year-old female with Glioblastoma multiforme (WHOIV) in the left temporal lobe. T2WI demonstrated a mass in the right temporal lobe near the left lateral ventricle, obviously enhanced on the Gd‐T1W image. The CBF map showed the masses with hypertransfusion. APTW image demonstrated the lesion with significant hyperintensity.

Table 1: Quantitative APTW values, CBF and AUC for treatment-related effect and recurrence Note: APTW values were recorded as average ± standard deviation (% of the water signal intensity) AUC is the area under the ROC curve Significant difference (p < 0.05) was marked by a *

Proc. Intl. Soc. Mag. Reson. Med. 27 (2019)