Quantitative MRI (qMRI) Metrics of Response to Stereotactic Radiosurgery for Brain Metastases

Brain metastases (BM) occur in 20-40 % of all cancer patients and stereotactic radiosurgery (SRS) is an important tool for BM therapy. However, response to therapy after SRS may take several months and is based on tumor dimension change. This study evaluated the predictive capacity of quantitative MRI (qMRI) for response to SRS, using chemical exchange saturation transfer (CEST) and magnetization transfer (MT). Fifty-four BM patients with 61 BM consented to this IRB approved prospective study. qMRI was conducted prior to and at 1-week after SRS treatment (single and hypo-fractionated). Response to SRS was evaluated according to RANO-BM. Tumors with CR, PR, and SD were considered responders (n = 40); tumors with PD or if the patient expired within 2 months after SRS were considered non-responders (n = 21). A single slice through BM was MRI-scanned (CEST & MT) on a 3T Philips scanner. Tumor ROI was identified on the post-Gd T1w and registered to the CEST slice. MT analysis provided the amount of MT, RM0B/RA, and direct water saturation, 1/(RAT2A) parameters. CEST analysis provided MTRAmide (3.5 ppm) and MTRrNOE (-3.5 ppm) that represent the combination of MT, direct saturation and CEST effects. Thus, using the MT analysis results, pure CESTAmide and CESTrNOE signals were also calculated (by removing MT and direct saturation effects from CEST data). The median age of patients was 58 years (35 F, 19 M) with BM most commonly from lung (30), followed by breast (11), melanoma (8), renal (3), liver (2), colon (2), GBM (1), rectum (1), cervix (1), H&N (1) and endometrial (1) cancers. Treatment was delivered in a single fraction with 18-20 Gy (n = 21), 24 Gy in 3 fractions (n = 2) and 25-30 Gy in 5 fractions (n = 38). Responders had a significant reduction in CESTAmide (prior 3.7 ± 1.0 [%], 1-week 3.0 ± 0.9 [%], p = 0.008) and MTRAmide (prior 9.5 ±1.5 [%], 1-week 8.8 ± 1.4 [%], p = 0.048) suggesting a reduction in metabolism. No change was observed for non-responders in CESTAmide (prior 2.8 ± 0.9 [%], 1-week 2.7 ± 0.9 [%], p = 0.77) and MTRAmide (prior 8.8 ± 1.2 [%], 1-week 8.2 ± 1.5 [%], p = 0.22). No other CEST or MT metric differentiated the 2 cohorts. Furthermore, when considering the pre-treatment scans only, we observed significant differences in CESTAmide properties of responders (3.7 ± 1.0 [%]) and non-responders (2.8 ± 0.9 [%]) with p = 0.004. The tumors that responded to SRS showed statistically significantly higher CESTAmide at the pre-treatment scan suggesting the less metabolically active tumors were resistant to radiotherapy. Tumors that respond to SRS experience significant reduction in CESTAmide after SRS while it does not change for non-responders. We also observe that at baseline, qMRI can determine a priori which tumors will subsequently respond to SRS, as those with greater metabolic activity even before treatment (characterized by CESTAmide), suggesting CEST can characterize tumor aggressiveness. Such information may be useful in prescribing the optimal treatment plan.