Rory J. Piper

Towards the automatic computational assessment of enlarged perivascular spaces on brain magnetic resonance images: A systematic review

Enlarged perivascular spaces (EPVS), visible in brain MRI, are an important marker of small vessel disease and neuroinflammation. We systematically evaluated the literature up to June 2012 on possible methods for their computational assessment and analyzed confounds with lacunes and small white matter hyperintensities. We found six studies that assessed/identified EPVS computationally by seven different methods, and four studies that described techniques to automatically segment similar structures and are potentially suitable for EPVS segmentation. T2‐weighted MRI was the only sequence that identified all EPVS, but FLAIR and T1‐weighted images were useful in their differentiation. Inconsistency within the literature regarding their diameter and terminology, and overlap in shape, intensity, location, and size with lacunes, conspires against their differentiation and the accuracy and reproducibility of any computational segmentation technique. The most promising approach will need to combine various MR sequences and consider all these features for accurate EPVS determination. J. Magn. Reson. Imaging 2013;38:774–785.

Application of diffusion tensor imaging and tractography of the optic radiation in anterior temporal lobe resection for epilepsy: a systematic review.

BACKGROUND Approximately 50-100% of patients with temporal lobe epilepsy undergoing anterior temporal lobe resection (ATLR) will suffer a postoperative visual field defect (VFD) due to disruption of the optic radiation (OpR). OBJECTIVE We conducted a systematic review of the literature to examine the role of DTI and tractography in ATLR and its potential in reducing the incidence of postoperative VFD. METHODS We conducted an electronic literature search using PubMed, Embase, Web of Science and BMJ case report databases. Eligibility for study inclusion was determined on abstract screening using the following criteria: the study must have been (1) an original investigation or case report in humans; (2) investigating the OpR with DTI in cases of ATLR in temporal lobe epilepsy; (3) investigating postoperative VFD. All forms of ATLR and ways of assessing VFD were included to reflect clinical practice. RESULTS 13 studies (four case reports, eight prospective observational studies, one prospective comparative trial) were included in the review, 179 (mean±SD, 13.8±12.6; range, 1-48) subjects were investigated using DTI. The time of postoperative VFD measurement differed between the detected studies, ranging from two weeks to nine years following ATLR. A modest number of studies and insufficient statistical homogeneity precluded meta-analysis. However, DTI methods were consistently accurate at quantifying and predicting postoperative damage to the OpR. These methods revealed a correlation between the extent of OpR damage and the severity of postoperative VFD. The first and only trial with 15 subjects compared to 23 controls reported that using intraoperative tractography in ATLR significantly reduces the occurrence of postoperative VFD on comparison to conventional surgical planning. CONCLUSIONS DTI shows potential to be an effective method used in planning ATLR. Findings from a single modest sized study suggest that tractography may be employed as part of intraoperative navigation techniques in order to avoid injury to the OpR. Further research needs to be conducted to ensure the applicability and effectiveness of this technology before implementation in routine clinical practice.

Development and initial evaluation of a semi-automatic approach to assess perivascular spaces on conventional magnetic resonance images.

Graphical abstract

Morphologic, Distributional, Volumetric, and Intensity Characterization of Periventricular Hyperintensities

These authors sought to characterize white matter lesions of elderly adults and determine if some were artifacts. Using FLAIR they imaged 665 subjects without dementia, carefully measured and evaluated periventricular white matter lesions, and correlated these with several aspects of cardiovascular disease. They concluded that periventricular white matter hyperintensity levels, distribution, and association with risk factors and disease suggest that in old age, these are true tissue abnormalities and therefore should not be dismissed as artifacts. BACKGROUND AND PURPOSE: White matter hyperintensities are characteristic of old age and identifiable on FLAIR and T2-weighted MR imaging. They are typically separated into periventricular or deep categories. It is unclear whether the innermost segment of periventricular white matter hyperintensities is truly abnormal or is imaging artifacts. MATERIALS AND METHODS: We used FLAIR MR imaging from 665 community-dwelling subjects 72–73 years of age without dementia. Periventricular white matter hyperintensities were visually allocated into 4 categories: 1) thin white line; 2) thick rim; 3) penetrating toward or confluent with deep white matter hyperintensities; and 4) diffuse ill-defined, labeled as “subtle extended periventricular white matter hyperintensities.” We measured the maximum intensity and width of the periventricular white matter hyperintensities, mapped all white matter hyperintensities in 3D, and investigated associations between each category and hypertension, stroke, diabetes, hypercholesterolemia, cardiovascular disease, and total white matter hyperintensity volume. RESULTS: The intensity patterns and morphologic features were different for each periventricular white matter hyperintensity category. Both the widths (r = 0.61, P < .001) and intensities (r = 0.51, P < .001) correlated with total white matter hyperintensity volume and with each other (r = 0.55, P < .001) for all categories with the exception of subtle extended periventricular white matter hyperintensities, largely characterized by evidence of erratic, ill-defined, and fragmented pale white matter hyperintensities (width: r = 0.02, P = .11; intensity: r = 0.02, P = .84). The prevalence of hypertension, hypercholesterolemia, and neuroradiologic evidence of stroke increased from periventricular white matter hyperintensity categories 1 to 3. The mean periventricular white matter hyperintensity width was significantly larger in subjects with hypertension (mean difference = 0.5 mm, P = .029) or evidence of stroke (mean difference = 1 mm, P < .001). 3D mapping revealed that periventricular white matter hyperintensities were discontinuous with deep white matter hyperintensities in all categories, except only in particular regions in brains with category 3. CONCLUSIONS: Periventricular white matter hyperintensity intensity levels, distribution, and association with risk factors and disease suggest that in old age, these are true tissue abnormalities and therefore should not be dismissed as artifacts. Dichotomizing periventricular and deep white matter hyperintensities by continuity from the ventricle edge toward the deep white matter is possible.

Medical student perceptions of research and research-orientated careers: An international questionnaire study

Abstract Background: Engaging and inspiring the next generation of physician-scientists at an early stage is recognised as key to ensure the future of medical research. However, little is known about medical student perceptions of research. Objectives: We attempted to ascertain perceptions of research and research-orientated careers from medical students studying in different countries. Methods: An online questionnaire was developed, piloted, and promoted to medical students in various countries. Results: 1625 responses were collected from 38 countries. Analysis was restricted to data collected from countries with >100 responses (n = 890). Less than half the respondents felt their medical school provided adequate research training. Key perceived barriers to research participation as a student included lack of time and difficulty finding mentors or projects. A significant gender disparity existed in research ambitions of students with females desiring less research involvement. The importance of barriers and satisfaction with research training differed significantly between countries. Conclusions: Students perceive a number of key barriers to research involvement and pursuit of research-orientated careers. Programmes designed to engage students with research should focus on overcoming identified barriers. Greater effort is needed to engage female students who report more significant barriers and less desire to follow research-orientated careers.

Focused ultrasound as a non-invasive intervention for neurological disease: a review.

Abstract Focused ultrasound (FUS) is an incision-less intervention that is a Food and Drug Association (FDA) approved surgical treatment for various pathologies including uterine fibroids and bone metastases. Recent advances in magnetic resonance imaging thermometry and ability to use FUS across the intact calvarium have re-opened interest in the use of FUS in the treatment of neurological diseases. FUS currently has a European CE mark for use in movement disorders. However, it shows potential in the treatment of other neuropathologies including tumours and as a lesional tool in epilepsy. FUS may exert its therapeutic effect through thermal or mechanical fragmentation of intracranial lesions, or by enhancing delivery of pharmaceutical agents across the blood–brain barrier. In this review, we summarise the mechanisms, clinical applications and potential future of FUS for the treatment of neurological disease. We have searched for and described the recently completed and on-going clinical trials investigating FUS for the treatment of neurological disorders. We identified phase one trials investigating utility of FUS in: movement disorders (including essential tremor and Parkinson’s disease), chronic pain, obsessive-compulsive disorder and cerebral tumours. Current literature also reports pre-clinical work exploring utility in epilepsy, neurodegenerative conditions (such as Alzheimer’s disease) and thrombolysis. Safety and early efficacy data are now emerging, suggesting that transcalvarial FUS is a feasible and safe intervention. Further evidence is required to determine whether FUS is an effective alternative in comparison to current neurosurgical interventions. The cost of requisite hardware is currently a barrier to widespread uptake in UK neurosurgical centres.

Imaging signatures of meningioma and low-grade glioma: a diffusion tensor, magnetization transfer and quantitative longitudinal relaxation time MRI study

Differentiation of cerebral tumor pathology currently relies on interpretation of conventional structural MRI and in some cases histology. However, more advanced MRI methods may provide further insight into the organization of cerebral tumors and have the potential to aid diagnosis. The objective of this study was to use multimodal quantitative MRI to measure the imaging signatures of meningioma and low-grade glioma (LGG). Nine adults with meningioma and 11 with LGG were identified, and underwent standard structural, quantitative longitudinal relaxation time (T1) mapping, magnetization transfer and diffusion tensor MRI. Maps of mean (〈D〉), axial (λAX) and radial (λRAD) diffusivity, fractional anisotropy (FA), magnetization transfer ratio (MTR) and T1 were generated on a voxel-by-voxel basis. Using structural and echo-planar T2-weighted MRI, manual region-of-interest segmentation of brain tumor, edema, ipsilateral and contralateral normal-appearing white matter (NAWM) was performed. Differences in imaging signatures between the different tissue types, both absolute mean values and ratios relative to contralateral NAWM, were assessed using t-tests with statistical significance set at p<0.05. For both absolute mean values and ratios relative to contralateral NAWM, there were significant differences in 〈D〉, λAX, λRAD, FA, MTR and T1 between meningioma and LGG tumor tissue, respectively. Only T1 and FA differed significantly between edematous tissue associated with the two tumor types. These results suggest that multimodal MRI biomarkers are significantly different, particularly in tumor tissue, between meningioma and LGG. By using quantitative multimodal MRI it may be possible to identify tumor pathology non-invasively.

Estimating intracranial volume using intracranial area in healthy children and those with childhood status epilepticus

Correcting volumetric measurements of brain structures for intracranial volume (ICV) is important in comparing volumes across subjects with different ICV. The aim of this study was to investigate whether intracranial area (ICA) reliably predicts actual ICV in a healthy pediatric cohort and in children with convulsive status epilepticus (CSE).

Intratumoral Heterogeneity of Tumor Infiltration of Glioblastoma Revealed by Joint Histogram Analysis of Diffusion Tensor Imaging

Purpose The purpose of this study is to propose a novel interpretation method of diffusion tensor imaging (DTI) using the joint histogram analysis of DTI-p and -q. With this method we explored the heterogeneity of tumor infiltration and examined the prognostic value of tumor infiltrative patterns for patient survival. Materials and methods A total of 115 primary glioblastoma patients (mean age 59.3 years, 87 males) were prospectively recruited from July 2010 to August 2015. Patients underwent preoperative MRI scans and maximal safe resection. DTI was processed and decomposed into p and q components. The univariate and joint histograms of DTI-p and -q were constructed using the pixels of contrast-enhancing and non-enhancing regions respectively. Eight joint histogram features were obtained and correlated with tumor progression rate and patient survival using cox-regression model. Their prognostic values were compared with clinical factors using receiver operating characteristic curves. Results The subregion of increased DTI-p and decreased DTI-q accounted for the largest proportion. Additional diffusion patterns can be identified via joint histogram analysis. Particularly, higher proportion of decreased DTI-p and increased DTI-q in non-enhancing region contributed to worse progression-free survival and overall survival (both HR = 1.12, p < 0.001); its proportion showed a positive correlation (p = 0.010, r = 0.35) with tumor progression rate. Conclusion Joint histogram analysis of DTI can provide a comprehensive measure of heterogeneity in infiltration, which showed prognostic values for glioblastoma patients. The subregion of decreased DTI-p and increased DTI-q in non-enhancing region may indicate a more invasive habitat. Funding This study was funded by a National Institute for Health Research (NIHR) Clinician Scientist Fellowship (SJP, project reference NIHR/CS/009/011); CRUK core grant C14303/A17197 and A19274 (FM lab); Cambridge Trust and China Scholarship Council (CL & SW); the Chang Gung Medical Foundation and Chang Gung Memorial Hospital, Keelung, Taiwan (JLY); CRUK & EPSRC Cancer Imaging Centre in Cambridge & Manchester (FM & TT, grant C197/A16465); Royal College of Surgeons of England (RS); NIHR Cambridge Biomedical Research Centre (TM & SJP). The Human Research Tissue Bank is supported by the NIHR Cambridge Biomedical Research Centre. We would like to acknowledge the support of National Institute for Health Research, the University of Cambridge, Cancer Research UK and Hutchison Whampoa Limited. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. Conflict of Interest none Advances in knowledge Joint histogram analysis of the isotropic (p) and anisotropic (q) components of the diffusion tensor imaging can reflect the intratumoral heterogeneity of glioblastoma infiltration. Incremental prognostic values for the prediction of overall survival and progression-free survival can be achieved by the joint histogram features, when integrated with IDH-1 mutation, MGMT methylation status and other clinical factors. The non-enhancing tumor subregion in which water molecules display decreased isotropic movement and increased anisotropic movement are potentially representative of a more invasive tumor habitat. Implications for patient care This study helps us to understand how the infiltrative patterns of glioblastoma contribute to patient outcomes. The invasive subregion identified by this approach may have clinical implications for personalized surgical resection and targeted radiation therapy. Summary Statement The joint histogram analysis may help to better understand the heterogeneity of tumor infiltration. The decreased DTI-p and increased DTI-q in non-enhancing region may be able to define an invasive subregion responsible for tumor progression.

Radiological Correlates of Raised Intracranial Pressure in Children: A Review.

Radiological assessment of the head is a routine part of the management of traumatic brain injury. This assessment can help to determine the requirement for invasive intracranial pressure (ICP) monitoring. The radiological correlates of elevated ICP have been widely studied in adults but far fewer specific pediatric studies have been conducted. There is, however, growing evidence that there are important differences in the radiological presentations of elevated ICP between children and adults; a reflection of the anatomical and physiological differences, as well as a difference in the pathophysiology of brain injury in children. Here in, we review the radiological parameters that correspond with increased ICP in children that have been described in the literature. We then describe the future directions of this work and our recommendations in order to develop non-invasive and radiological markers of raised ICP in children.