Phantom and Digital Reference Object Literature Inventory

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Several digital reference objects (DROs) for DCE-MRI have been created to test the accuracy of pharmacokinetic modeling software under a variety of different noise conditions. However, there are few DROs that mimic the anatomical distribution of voxels found in real data, and similarly few DROs that are based on both malignant and normal tissue. We propose a series of DROs for modeling Ktrans and Ve derived from a publically-available RIDER DCEMRI dataset of 19 patients with gliomas. For each patient’s DCE-MRI data, we generate Ktrans and Ve parameter maps using an algorithm validated on the QIBA Tofts model phantoms. These parameter maps are denoised, and then used to generate noiseless time-intensity curves for each of the original voxels. This is accomplished by reversing the Tofts model to generate concentration-times curves from Ktrans and Ve inputs, and subsequently converting those curves into intensity values by normalizing to each patient’s average pre-bolus image intensity. The result is a noiseless DRO in the shape of the original patient data with known ground-truth Ktrans and Ve values. We make this dataset publically available for download for all 19 patients of the original RIDER dataset.

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PURPOSE: Dynamic susceptibility contrast (DSC)-MRI is a perfusion imaging technique from which useful quantitative imaging biomarkers can be derived. Relative cerebral blood volume (rCBV) is such a biomarker commonly used for evaluating brain tumors. To account for the extravasation of contrast agents in tumors, post-processing leakage correction is often applied to improve rCBV accuracy. Digital reference objects (DRO) are ideal for testing the post-processing software, because the biophysical model used to generate the DRO can be matched to the one that the software uses. This study aims to develop DROs to validate the leakage correction of software using Weisskoff model and to examine the effect of background signal time curves that are required by the model. METHODS: Three DROs were generated using the Weisskoff model, each composed of nine foreground lesion objects with combinations of different levels of rCBV and contrast leakage parameter (K2). Three types of background were implemented for these DROs: (1) a multi-compartment brain-like background, (2) a sphere background with a constant signal time curve, and (3) a sphere background with signal time curve identical to that of the brain-like DRO's white matter (WM). The DROs were then analyzed with an FDA-cleared software with and without leakage correction. Leakage correction was tested with and without brain segmentation. RESULTS: Accuracy of leakage correction was able to be verified using the brain-like phantom and the sphere phantom with WM background. The sphere with constant background did not perform well with leakage correction with or without brain segmentation. The DROs were able to verify that for the particular software tested, leakage correction with brain segmentation achieved the lowest error. CONCLUSIONS: DSC-MRI DROs with biophysical model matched to that of the post-processing software can be well used for the software's validation, provided that the background signals are also properly simulated for generating the reference time curve required by the model. Care needs to be taken to consider the interaction of the design of the DRO with the software's implementation of brain segmentation to extract the reference time curve.

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The standardization and broad-scale integration of dynamic susceptibility contrast (DSC)-magnetic resonance imaging (MRI) have been confounded by a lack of consensus on DSC-MRI methodology for preventing potential relative cerebral blood volume inaccuracies, including the choice of acquisition protocols and postprocessing algorithms. Therefore, we developed a digital reference object (DRO), using physiological and kinetic parameters derived from in vivo data, unique voxel-wise 3-dimensional tissue structures, and a validated MRI signal computational approach, aimed at validating image acquisition and analysis methods for accurately measuring relative cerebral blood volume in glioblastomas. To achieve DSC-MRI signals representative of the temporal characteristics, magnitude, and distribution of contrast agent-induced T1 and T2* changes observed across multiple glioblastomas, the DRO's input parameters were trained using DSC-MRI data from 23 glioblastomas (>40 000 voxels). The DRO's ability to produce reliable signals for combinations of pulse sequence parameters and contrast agent dosing schemes unlike those in the training data set was validated by comparison with in vivo dual-echo DSC-MRI data acquired in a separate cohort of patients with glioblastomas. Representative applications of the DRO are presented, including the selection of DSC-MRI acquisition and postprocessing methods that optimize CBV accuracy, determination of the impact of DSC-MRI methodology choices on sample size requirements, and the assessment of treatment response in clinical glioblastoma trials.

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