Oxygen-enhanced MRI MOLLI T1 mapping during chemoradiotherapy in anal squamous cell carcinoma

Abstract

a b s t r a c tBackground and purpose: Oxygen-enhanced magnetic resonance imaging (MRI) and T1-mapping was used to explore its effectiveness as a prognostic imaging biomarker for chemoradiotherapy outcome in anal squamous cell carcinoma. Materials and methods: T2-weighted, T1 mapping, and oxygen-enhanced T1 maps were acquired before and after 8-10 fractions of chemoradiotherapy and examined whether the oxygen-enhanced MRI response relates to clinical outcome. Patient response to treatment was assessed 3 months following completion of chemoradiotherapy. A mean T1 was extracted from manually segmented tumour regions of interest and a paired two-tailed t-test was used to compare changes across the patient population. Regions of subcutaneous fat and muscle tissue were examined as control ROIs. Results: There was a significant increase in T1 of the tumour ROIs across patients following the 8-10 fractions of chemoradiotherapy (paired t-test, p < 0.001, n = 7). At baseline, prior to receiving chemoradiotherapy, there were no significant changes in T1 across patients from breathing oxygen (n = 9). In the post-chemoRT scans (8-10 fractions), there was a significant decrease in T1 of the tumour ROIs across patients when breathing 100% oxygen (paired t-test, p < 0.001, n = 8). Out of the 12 patients from which we successfully acquired a visit 1 T1-map, only 1 patient did not respond to treatment, therefore, we cannot correlate these results with clinical outcome. Conclusions: These clinical data demonstrate feasibility and potential for T1-mapping and oxygen enhanced T1-mapping to indicate perfusion or treatment response in tumours of this nature. These data show promise for future work with a larger cohort containing more non-responders, which would allow us to relate these measurements to clinical outcome.

First-in-human technique translation of oxygen-enhanced MRI to an MR Linac system in patients with head and neck cancer

“…Prior to this study, we and others have demonstrated that OE-MRI can induce signal changes in healthy tissues [16,34], can identify, quantify and map hypoxic sub-regions in mouse [17][18], rat [19], rabbit [35] and human [36][37][38][39] tumours, and can track response to therapy in patients with lung cancer [18]. While our previous work has focused on the value of OE-MRI combined with a perfusion sequence to exclude necrosis [17][18], most of the studies listed above from other groups tend to perform OE-MRI without this additional step.…”

Oxygen-enhanced MRI and radiotherapy in patients with oropharyngeal squamous cell carcinoma

“…Applying OE-MRI into a clinical trial workflow heightens the importance of two relevant factors: acquisition time and patient motion. Patient motion is especially detrimental if the original region of interest moves out of the imaging field-of-view, which has also occurred in previous OE-MRI studies using 2D rather than 3D imaging techniques [38] , [61] . In this current study, patient motion was a nontrivial concern: patient motion in the z-plane occurred in 7/12 patients, resulting in the MOLLI T1 map capturing a different section of the tumour, rendering it unusable for OE-MRI analysis.…”

“…Unfortunately, the T2* maps in this study were excluded due to artefacts, so it was not possible to discern the underlying source of this positive ΔR1 ox-air observed in the non-responder, however this demonstrates the importance of the inclusion of other measurements in the MRI protocol such as R2*. Therefore, although this study contained a small sample size (n = 5, other published OE-MRI clinical data has contained 4 [34] , 5 [13] , 6 [14] , 7 [37] , 7–9 [38] , 10 [17] , and 15 [18] subjects), the OE-MRI responses observed were consistent with the underlying OE-MRI theory and previously reported tumour OE-MRI responses.…”

“…Over the years, OE-MRI studies have used a variety of methods to detect the change in R1 – some have used semi-quantitative signal intensity changes in T1-weighted imaging [12] , [19] , [35] , [51] , [52] , and some have used quantitative T1 mapping methods such as inversion recovery [13] , [22] , [25] , [53] , [54] , [55] , saturation recovery [56] , VFA [11] , [39] , [50] , [57] , [17] , [18] , [19] , or Look-Locker variants such as MOLLI [28] , [34] , [38] , [58] , [59] . There are tradeoffs between T1 estimation accuracy and acquisition time between each of these methods, and some are known to overestimate (VFA) or underestimate (Look-Locker variants) the true T1 of the material [60] , with inversion recovery being the ‘gold-standard’ technique.…”

“…After showing promising results in preclinical studies measuring hypoxia [9] , [10] , [13] , [14] , [16] , [19] or radiation response [12] , [18] , [35] , [36] , the OE-MRI methodology has continued to be refined for clinical applications, with some analysis techniques being proposed to improve the signal-to-noise ratio, acquisition time, and to improve the robustness of the technique for use in human patients [11] , [15] . To date, 8 human studies have used variations of the OE-MRI method in tumours: 4 patients with brain metastasis and glioma [34] , 5 patients with glioblastoma [13] , 6 patients with renal carcinoma [14] , 7 patients with intracranial tumours [37] , 7–9 patients with anal squamous cell carcinoma [38] , 10 patients with brain metastasis [17] , 10 patients with cervical and hepatocellular carcinoma or metastases from ovarian and colorectal carcinomas [39] , and 15 patients with non small cell lung cancer [18] , with 3 of the 8 studies involving any radiotherapy treatment. In each case, the OE-MRI method has repeatedly been shown to be well-tolerated by patients.…”