USPIO Enhanced MR Imaging in CNS Tumours (UMIC) : A Pilot Study of Ferumoxytol (Feraheme ©) as an Imaging Biomarker of Tumour Associated Macrophage (TAM) Infiltration in Vestibular Schwannoma (VS) and Transforming Low Grade Glioma (LGG)
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 17
- 试验地点
- 2
- 主要终点
- Establish in a cohort of surgically resected sporadic VS if the enhancement pattern of delayed (24-48 hr) USPIO uptake correlates with tissue markers of TAM density and tissue microvascular markers.
研究概览
简要总结
The immune response or inflammation is known to be a key driver of progression and growth in many solid tumours. Inflammatory cells called macrophages are present in high numbers in many brain tumours and these tumour associated macrophages or TAM are thought to have prognosis and treatment implications in these tumours. A key question, however, is how this inflammation or TAM abundance can be detected, measured and monitored in the clinic. A clinically applicable imaging test that can directly and accurately measure tumour macrophage content would be of considerable value and one technique that may provide this is USPIO enhanced magnetic resonance imaging (MRI). Following intravenous injection, USPIO or ultrasmall superparamagnetic iron oxide nanoparticles, circulate in the bloodstream before being taken up by inflammatory cells/macrophages in tumour tissue, wherein they can be detected by MRI. This pilot study is to evaluate if a commercially available USPIO preparation called ferumoxytol (Feraheme ©) can accurately quantify macrophage abundance in brain tumours, with an exploratory focus on vestibular schwannoma (VS) and suspected transforming low-grade glioma (LGG). Patients with both non-growing (static) and growing VS, and patients with suspected transforming LGG will undergo dedicated MRI sequences before, immediately after (< 2 hours) and at both 24 and 48hrs after ferumoxytol administration. In patients undergoing surgery, acquired imaging will be compared with resected tumour tissue so that markers of inflammation can be compared with USPIO uptake. Through advanced laboratory methods this study will seek to establish within resected VS and LGG specimens: the cellular destination/s of USPIO uptake; the nature of the inflammatory and/or tumour cells containing the USPIO; and the relationship between USPIO uptake and tumour blood vessel permeability or leakiness.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 16 Years 至 100 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Be at least 16 years old
- •Have a CNS tumour suspected to be one of the defined histological types (vestibular scwhannoma or low grade glioma)
- •Be able to lie still for up to 1 hour comfortably
- •Opinion of the treating clinician is that the patient will be able to successfully complete the research imaging protocol.
排除标准
- •Life expectancy less than 1 year
- •Previous CNS radiotherapy/ stereotactic radiosurgery (SRS)
- •Females who are pregnant/ breastfeeding
- •Patients with an eGFR < 30ml/min
- •Patients with known and documented history of iron overload/haemosiderosis/ haemochromatosis
- •Patients with immune or inflammatory conditions e.g. systemic lupus erythematous, rheumatoid arthritis
- •Patients with absolute (e.g. pacemaker) and relative (anxiety or claustrophobia) contraindications to MR scanning
- •Patients with a history of allergic reaction to iron or dextran
- •Patients with a history of allergic reaction to gadolinium contrast agents, asthma or renal problems
- •Patients who are unable to adequately understand verbal explanations or written information given in English.
结局指标
主要结局
Establish in a cohort of surgically resected sporadic VS if the enhancement pattern of delayed (24-48 hr) USPIO uptake correlates with tissue markers of TAM density and tissue microvascular markers.
时间窗: Three years
Use correlation tests to establish the relationship between delayed (24-48 hr) USPIO related MRI signal intensity changes and tissue markers of TAM density and microvascular markers.
Evaluate the association between microvascular parameters derived from dynamic contrast enhanced (DCE) MRI) and the volume, pattern and intensity of early (<2hr) and delayed (24-48 hr) USPIO imaging in these tumours.
时间窗: Three years
Use voxelwise correlation tests and ROI analysis to establish the relationship between microvascular parameters derived from dynamic contrast enhanced (DCE) MRI) and USPIO related signal intensity changes at early (\<2hr) and delayed (24-48 hr) imaging timepoints in these tumours.
Establish within resected VS and transforming low-grade glioma specimens the cellular destination/s of USPIO internalisation and the in vivo relationship between BBB disruption and USPIO extravasation.
时间窗: Three years
Immunohistochemistry (IHC)/ immunofluorescence will be used on both formalin fixed paraffin embedded (FFPE) and frozen tissue samples to map the uptake of USPIO within immune and non-immune cell populations.
Establish the relationship between enhancement patterns following GBCA administration and the volume, pattern and intensity of early (<2hr) and delayed (24-48 hr) USPIO imaging in these tumours.
时间窗: Three years
Differences in the enhancement pattern between post GBCA T1W images and the delayed (24-48hr) ferumoxytol enhanced T1W images will be compared through visual inspection and use of the structural similarity index
Establish in VS the relationship between the volume, pattern and intensity of early (<2hr) and delayed (24-48 hr) USPIO imaging in these tumours with tumour size and tumour growth status (non-growing or static vs growing).
时间窗: Three years
Evaluate using appropriate parametric and non-parametric statistical tests if there are differences between non-growing and growing VS in USPIO related signal intensity changes on acquired T1, T2 and T2\* weighted imaging at early (\<2hr) and delayed (24-48 hr) imaging timepoints. Evaluate using correlation and regression analyses if there is a relationship between tumour size and USPIO related signal intensity changes on acquired T1, T2 and T2\* weighted imaging at early (\<2hr) and delayed (24-48 hr) imaging timepoints.
Establish if the enhancement pattern of delayed (24-48 hr) USPIO uptake correlates with loco-regional tissue markers of immune cell infiltration and malignant transformation within imaged transforming low grade glioma.
时间窗: Three years
Evaluate using appropriate parametric and non-parametric statistical tests if there are differences in USPIO related signal intensity changes and immune cell infiltration within regions of histologically proven transformation when compared to non-transformed areas.
次要结局
未报告次要终点