Matthew Grech-Sollars

Multi-centre reproducibility of diffusion MRI parameters for clinical sequences in the brain.

The purpose of this work was to assess the reproducibility of diffusion imaging, and in particular the apparent diffusion coefficient (ADC), intra‐voxel incoherent motion (IVIM) parameters and diffusion tensor imaging (DTI) parameters, across multiple centres using clinically available protocols with limited harmonization between sequences.

An MRS- and PET-guided biopsy tool for intraoperative neuronavigational systems

OBJECTIVE Glioma heterogeneity and the limitations of conventional structural MRI for identifying aggressive tumor components can limit the reliability of stereotactic biopsy and, hence, tumor characterization, which is a hurdle for developing and selecting effective treatment strategies. In vivo MR spectroscopy (MRS) and PET enable noninvasive imaging of cellular metabolism relevant to proliferation and can detect regions of more highly active tumor. Here, the authors integrated presurgical PET and MRS with intraoperative neuronavigation to guide surgical biopsy and tumor sampling of brain gliomas with the aim of improving intraoperative tumor-tissue characterization and imaging biomarker validation. METHODS A novel intraoperative neuronavigation tool was developed as part of a study that aimed to sample high-choline tumor components identified by multivoxel MRS and 18F-methylcholine PET-CT. Spatially coregistered PET and MRS data were integrated into structural data sets and loaded onto an intraoperative neuronavigation system. High and low choline uptake/metabolite regions were represented as color-coded hollow spheres for targeted stereotactic biopsy and tumor sampling. RESULTS The neurosurgeons found the 3D spherical targets readily identifiable on the interactive neuronavigation system. In one case, areas of high mitotic activity were identified on the basis of high 18F-methylcholine uptake and elevated choline ratios found with MRS in an otherwise low-grade tumor, which revealed the possible use of this technique for tumor characterization. CONCLUSIONS These PET and MRI data can be combined and represented usefully for the surgeon in neuronavigation systems. This method enables neurosurgeons to sample tumor regions based on physiological and molecular imaging markers. The technique was applied for characterizing choline metabolism using MRS and 18F PET; however, this approach provides proof of principle for using different radionuclide tracers and other MRI methods, such as MR perfusion and diffusion.

Challenges for the functional diffusion map in pediatric brain tumors

Background The functional diffusion map (fDM) has been suggested as a tool for early detection of tumor treatment efficacy. We aim to study 3 factors that could act as potential confounders in the fDM: areas of necrosis, tumor grade, and change in tumor size. Methods Thirty-four pediatric patients with brain tumors were enrolled in a retrospective study, approved by the local ethics committee, to examine the fDM. Tumors were selected to encompass a range of types and grades. A qualitative analysis was carried out to compare how fDM findings may be affected by each of the 3 confounders by comparing fDM findings to clinical image reports. Results Results show that the fDM in areas of necrosis do not discriminate between treatment response and tumor progression. Furthermore, tumor grade alters the behavior of the fDM: a decrease in apparent diffusion coefficient (ADC) is a sign of tumor progression in high-grade tumors and treatment response in low-grade tumors. Our results also suggest using only tumor area overlap between the 2 time points analyzed for the fDM in tumors of varying size. Conclusions Interpretation of fDM results needs to take into account the underlying biology of both tumor and healthy tissue. Careful interpretation of the results is required with due consideration to areas of necrosis, tumor grade, and change in tumor size.

Stability and reproducibility of co-electrospun brain-mimicking phantoms for quality assurance of diffusion MRI sequences

ABSTRACT Grey and white matter mimicking phantoms are important for assessing variations in diffusion MR measures at a single time point and over an extended period of time. This work investigates the stability of brain‐mimicking microfibre phantoms and reproducibility of their MR derived diffusion parameters. The microfibres were produced by co‐electrospinning and characterized by scanning electron microscopy (SEM). Grey matter and white matter phantoms were constructed from random and aligned microfibres, respectively. MR data were acquired from these phantoms over a period of 33 months. SEM images revealed that only small changes in fibre microstructure occurred over 30 months. The coefficient of variation in MR measurements across all time‐points was between 1.6% and 3.4% for MD across all phantoms and FA in white matter phantoms. This was within the limits expected for intra‐scanner variability, thereby confirming phantom stability over 33 months. These specialised diffusion phantoms may be used in a clinical environment for intra and inter‐site quality assurance purposes, and for validation of quantitative diffusion biomarkers. HIGHLIGHTSGrey and white matter mimicking phantoms showed mean diffusivity and fractional anisotropy values typical of tissue.Diffusion measures for the phantoms were stable over 33 months.The porosity of the phantoms was observed to be stable over 30 months.The phantoms may be used for QA purposes in a clinical environment and for validation of quantitative diffusion biomarkers.

Response to “Reply to ‘Survival analysis for apparent diffusion coefficient measures in children with embryonal brain tumors,’ by Grech-Sollars et al”

Dear Editor, We would like to thank Dr Korgun Koral, Dr Daniel C. Bowers, and Dr Robert Timmerman for their thoughts on our publication1 and would like to take the opportunity to respond to their comments. The main issue brought up is that of heterogeneity. Although we understand the concern expressed on this point, it is important to keep in mind that heterogeneity amongst the patient cohort would generally be expected to mask the effects of interest, rather than enhance them. For example, the lower survival in medulloblastoma patients having metastasis at presentation may be masked by including other tumor types, such as supratentorial primitive neuroectodermal tumors, where conflicting evidence exists as to whether there is a relationship between metastasis at presentation and survival. In a similar way, one would expect the relationship between survival and the apparent transient coefficient in tumor (ATCT) to be masked by cohort heterogeneity, if it is dependent on tumor type. Therefore, the fact that ATCT was significant across embryonal tumor types actually makes a stronger case for it to be considered as a measure of prognosis in addition to currently used variables. Although different tumor subtypes have different prognoses, this does not imply that ATCT cannot be a useful indicator of longer survival across all of them. Since there was no evidence in our data to suggest that patients with one or another tumor type did not fit the general pattern, the results may be said to broadly apply in all cases. By contrast, restricting the analysis to a very homogeneous sample severely restricts the generalizability of the conclusions that can be drawn. With that said, having separately analyzed the medulloblastoma patient group, we do recommend examining the ATCT by medulloblastoma subgroups in order to examine the predictive value of the ATCT compared with histological and molecular classifications. We also note that currently the presence of leptomeningeal metastasis and extent of tumor resection affect survival significantly, with specific treatment recommendations carried out based on these variables. In our study, both have been included and analyzed. Our results have shown ATCT to be a stronger indicator of survival than either of these 2 variables. We acknowledge that the rising incidence of atypical teratoid/rhabdoid tumors in young children is a factor that may contribute to the lower survival in children with embryonal brain tumors younger than 3 years of age. That said, age is a factor considered in determining treatment options for medulloblastoma patients,2 and our study showed that the difference in survival by age is also reflected in this subgroup of embryonal brain tumors. In conclusion, far from undermining our results, cohort heterogeneity reinforces the strength of ATCT as a biomarker of survival across a range of embryonal tumor types. Nonetheless, further analysis on larger patient groups of a more homogeneous nature would aid in identifying those groups in which it would be most beneficial to incorporate ATCT as part of clinical trials and as a biomarker of survival.