Design, data management, and population baseline characteristics of the PERFORM magnetic resonance imaging project

Abstract

Quantitative information from magnetic resonance imaging (MRI) may substantiate clinical findings and provide additional insight into the mechanism of clinical interventions in therapeutic stroke trials. The PERFORM study is exploring the efficacy of terutroban versus aspirin for secondary prevention in patients with a history of ischemic stroke. We report on the design of an exploratory longitudinal MRI follow-up study that was performed in a subgroup of the PERFORM trial. An international multi-centre longitudinal follow-up MRI study was designed for different MR systems employing safety and efficacy readouts: new T2 lesions, new DWI lesions, whole brain volume change, hippocampal volume change, changes in tissue microstructure as depicted by mean diffusivity and fractional anisotropy, vessel patency on MR angiography, and the presence of and development of new microbleeds. A total of 1,056 patients (men and women ≥ 55 years) were included. The data analysis included 3D reformation, image registration of different contrasts, tissue segmentation, and automated lesion detection. This large international multi-centre study demonstrates how new MRI readouts can be used to provide key information on the evolution of cerebral tissue lesions and within the macrovasculature after atherothrombotic stroke in a large sample of patients.

Fig. 1

The trial profile of the PERFORM MRI project

Fig. 2

Lesion detection. From left to right, hyperintense FLAIR lesions, hypointense FLAIR lesions, and hyperintense DWI lesions were pre-detected using an unsupervised 3D segmentation algorithm after skull removal, and manually validated prior to submission to readers

Fig. 3

Brain parenchyma detection. Brain parenchyma contours (in red) was pre-detected using a 3D segmentation algorithm on 3DT1 images by 3D deformable registration of a brain atlas, after skull removal, and manually validated prior to submission to the readers. Interhemispheric plane is shown in yellow

Fig. 4

Hippocampus detection. Hippocampal contours (in red) were pre-detected using a semi-automatic technique prior to submission to the readers for confirmation

Fig. 5

Intracranial cavity detection. The T2* sequence was used to detect the intracranial cavity contours (in red) as it clearly depicts external CSF (left). Given the lack of full brain coverage for all patients the 3DT1 sequence was automatically coregistered to T2*, resliced in the axial plane, and used to manually complete for potentially missing upper and lower slices (right)

Fig. 6

Microbleeds assessment. Cerebral microbleeds, defined as punctuate, homogeneous, rounded, hypointense lesions smaller than 5 mm in size, visualised on T2* sequences, (in red), were counted throughout the brain by the readers, and classified as cortical, cortico-subcortical, juxtacortical or deep and infratentorial