Mark Radon

The role of magnetic resonance imaging in the management of brain metastases: diagnosis to prognosis

This article reviews the different MRI techniques available for the diagnosis, treatment and monitoring of brain metastases with a focus on applying advanced MR techniques to practical clinical problems. Topics include conventional MRI sequences and contrast agents, functional MR imaging, diffusion weighted MR, MR spectroscopy and perfusion MR. The role of radiographic biomarkers is discussed as well as future directions such as molecular imaging and MR guided high frequency ultrasound.

Anatomic Localization of Dyskinesia in Children with “Profound” Perinatal Hypoxic-Ischemic Injury

BACKGROUND AND PURPOSE: CP is a common feature of perinatal HIBD in the context of “acute profound” injury, and in this article, we have studied the possible anatomic substrates of dyskinesia. We have reviewed the extent of brain injury in children with dyskinetic and spastic CP due to acute profound hypoxia to identify sites of injury that explain why only some children develop movement disorders. It is known that the STN has a role in the development of movement disorders; therefore, we have specifically studied it. MATERIALS AND METHODS: We retrospectively reviewed MR imaging of 40 consecutive children referred to our center with CP confirmed to be due to acute profound hypoxic-ischemic injury. All children received the same high-resolution MR imaging protocol with the same 1.5T scanner. Two pediatric neuroradiologists reviewed the imaging. Logistic regression was applied to identify multivariable predictors that differentiate dyskinetic and spastic CP. RESULTS: Twenty children had dyskinetic CP and 20 had spastic CP. Children with dyskinetic CP had more frequent injury to the STN, as manifest by increased T2 signal intensity. Children with spastic CP had more severe damage to white matter in the vicinity of the paracentral lobule. Injuries to the putamen, caudate, and globus pallidus were not significant predictors of dyskinesia. CONCLUSIONS: We have shown an association between hypoxic-ischemic injury to the STN at birth and the emergence of dyskinesia later in life.

Diffusion-weighted MRI characteristics of the cerebral metastasis to brain boundary predicts patient outcomes

BackgroundDiffusion-weighted MRI (DWI) has been used in neurosurgical practice mainly to distinguish cerebral metastases from abscess and glioma. There is evidence from other solid organ cancers and metastases that DWI may be used as a biomarker of prognosis and treatment response. We therefore investigated DWI characteristics of cerebral metastases and their peritumoral region recorded pre-operatively and related these to patient outcomes.MethodsRetrospective analysis of 76 cases operated upon at a single institution with DWI performed pre-operatively at 1.5T. Maps of apparent diffusion coefficient (ADC) were generated using standard protocols. Readings were taken from the tumor, peritumoral region and across the brain-tumor interface. Patient outcomes were overall survival and time to local recurrence.ResultsA minimum ADC greater than 919.4 × 10-6 mm2/s within a metastasis predicted longer overall survival regardless of adjuvant therapies. This was not simply due to differences between the types of primary cancer because the effect was observed even in a subgroup of 36 patients with the same primary, non-small cell lung cancer. The change in diffusion across the tumor border and into peritumoral brain was measured by the “ADC transition coefficient” or ATC and this was more strongly predictive than ADC readings alone. Metastases with a sharp change in diffusion across their border (ATC >0.279) showed shorter overall survival compared to those with a more diffuse edge. The ATC was the only imaging measurement which independently predicted overall survival in multivariate analysis (hazard ratio 0.54, 95% CI 0.3 – 0.97, p = 0.04).ConclusionsDWI demonstrates changes in the tumor, across the tumor edge and in the peritumoral region which may not be visible on conventional MRI and this may be useful in predicting patient outcomes for operated cerebral metastases.

Management of Typical and Atypical Hangman's Fractures

Study Design Retrospective study of a prospectively maintained database. Objective Our aim was to retrospectively review management and outcomes of patients with low-grade hangmans fractures, specifically looking at differences in outcomes between collars and halo immobilization. We also studied fracture patterns and their treatment outcomes. Methods Forty-one patients with hangmans fractures were identified from 105 patients with axis fractures between 2007 and 2013. Typical hangmans fractures were defined as traumatic spondylolisthesis of the axis causing a bilateral pars interarticularis fracture. Fractures involving the posterior cortex of C2 on one or both sides or an asymmetrical pattern were defined as atypical. Results There were 41 patients with a mean age of 59 years, with 13 (31.7%) typical and 28 (68.2%) atypical fractures. There were 22 (53.6%) type 1 fractures, 7 (41.4%) type 2 fractures, and 2 (4.9%) type 2a fractures in this series. Cervical collars were used to manage 11 patients (27% of all patients with hangmans fractures) and halo orthosis was used in 27 (65.8%). Three (7.3%) patients underwent surgical fixation of the fracture. Bony union was achieved in all patients on radiologic follow-up. Permanent neurologic deficit occurred in one patient due to associated injuries. Neck pain and stiffness were reported more commonly in the atypical group, but this finding was not statistically significant. Conclusions The majority of hangman type fractures can be treated nonoperatively. We found no difference in outcomes between a rigid collar or halo immobilization for treatment of low-grade fractures. Radiologic follow-up is essential to identify cases of nonunion.

The reliability of routine clinical post-processing software in assessing potential diffusion-weighted MRI “biomarkers” in brain metastases

BACKGROUND AND PURPOSE Diffusion MRI characteristics have been used as biomarkers to guide prognosis in cerebral pathologies including brain metastases. The measurement of ADC is often described poorly in clinical and research studies with little detail given to the practical considerations of where to place ROIs, which post processing software package to use and how reproducible the resulting metrics will be. METHOD We investigated a series of 12 patients with brain metastases and preoperative DWI. Three post processing platforms were used. ROI were placed over the tumour, peritumoural region and across the brain-tumour interface. These recordings were made by a neurosurgeon and a neuroradiologist. Inter-intra-observer variability was assessed using Bland-Altman analysis. An exploratory analysis of DWI with overall survival and tumour type was made. RESULTS There was excellent correlation between the software packages used for all measures including assessing the whole tumour, selective regions with lowest ADC, the change of ADC across the brain-tumour interface and the relation of the tumour ADC to peritumoural regions and the normal white matter. There was no significant inter- or intra-observer variability for repeated readings. There were significant differences in the mean values obtained using different methodologies and different metrics had differing relationships to overall survival and primary tumour of origin. CONCLUSION Diffusion weighted MRI metrics offer promise as potential non-invasive biomarkers in brain metastases and a variety of metrics have been shown to be reliably measured using differing platforms and observers.

Accuracy of four-dimensional CT angiography in detection and characterisation of arteriovenous malformations and dural arteriovenous fistulas.

A retrospective review was made to assess the accuracy of four dimensional CT angiogram (4D-CTA) in diagnosis of arteriovenous malformations (AVM) and dural arteriovenous fistulas (DAVF), with catheter-based digital-subtraction angiogram (DSA) being gold standard. 33 pairs of investigations (DSA and 4D-CTA) were performed primarily for suspicion of AVM/DAVF. Based on blinded reports, sensitivity and specificity for detection of AVM/DAVF were 77% (95% CI: 46 - 95%) and 100% (95% CI: 83 - 100%) respectively. Positive predictive value was 100% (95% CI: 69 - 100%) and negative predictive value 87% (95% CI: 66-97%). 4D-CTA is a practical minimally-invasive technique for evaluating cerebrovascular pathologies. There is good agreement between the findings of 4D-CTA and DSA despite the differences in temporal and spatial resolutions. 4D-CTA may obviate the need for DSA in a subgroup of patients who would otherwise have undergone this invasive investigation, which carries a risk of important complications.

Novel use of 4D-CTA in imaging of intranidal aneurysms in an acutely ruptured arteriovenous malformation: is this the way forward?

Ruptured arteriovenous malformation (AVM) is a frequent cause of intracranial hemorrhage. The presence of associated aneurysms, especially intranidal aneurysms, is considered to increase the risk of re-hemorrhage. We present two cases where an intranidal aneurysm was demonstrated on four-dimensional CT angiography (time-resolved CT angiography) (4D-CTA). These features were confirmed by digital subtraction angiography (catheter arterial angiogram). This is the first report of an intranidal aneurysm demonstrated by 4D-CTA. 4D-CTA can offer a comprehensive evaluation of the angioarchitecture and flow dynamics of an AVM for appropriate classification and management.

T cell densities in brain metastases are associated with patient survival times and diffusion tensor MRI changes

Brain metastases are common and are usually detected by MRI. Diffusion tensor imaging (DTI) is a derivative MRI technique that can detect disruption of white matter tracts in the brain. We have matched preoperative DTI with image-guided sampling of the brain-tumor interface in 26 patients during resection of a brain metastasis and assessed mean diffusivity and fractional anisotropy (FA). The tissue samples were analyzed for vascularity, inflammatory cell infiltration, growth pattern, and tumor expression of proteins associated with growth or local invasion such as Ki67, S100A4, and MMP2, 9, and 13. A lower FA in the peritumoral region indicated more white matter tract disruption and independently predicted longer overall survival times (HR for death = 0.21; 95% confidence interval, 0.06-0.82; P = 0.024). Of all the biological markers studied, only increased density of CD3+ lymphocytes in the same region correlated with decreased FA (Mann-Whitney U, P = 0.037) as well as confounding completely the effect of FA on multivariate survival analyses. We conclude that the T-cell response to brain metastases is not a surrogate of local tumor invasion, primary cancer type, or aggressive phenotype and is associated with patient survival time regardless of these biological factors. Furthermore, it can be assayed by DTI, potentially offering a quick, noninvasive, clinically available method to detect an active immune microenvironment and, in principle, to measure susceptibility to immunotherapy.Significance: These findings show that white matter tract integrity is degraded in areas where T-cell infiltration is highest, providing a noninvasive method to identify immunologically active microenvironments in secondary brain tumors. Cancer Res; 78(3); 610-6. ©2017 AACR.

Quantification of structural changes in the corpus callosumin children with profound hypoxic–ischaemic brain injury

BackgroundBirth-related acute profound hypoxic–ischaemic brain injury has specific patterns of damage including the paracentral lobules.ObjectiveTo test the hypothesis that there is anatomically coherent regional volume loss of the corpus callosum as a result of this hemispheric abnormality.Materials and methodsStudy subjects included 13 children with proven acute profound hypoxic–ischaemic brain injury and 13 children with developmental delay but no brain abnormalities. A computerised system divided the corpus callosum into 100 segments, measuring each width. Principal component analysis grouped the widths into contiguous anatomical regions. We conducted analysis of variance of corpus callosum widths as well as support vector machine stratification into patient groups.ResultsThere was statistically significant narrowing of the mid–posterior body and genu of the corpus callosum in children with hypoxic–ischaemic brain injury. Support vector machine analysis yielded over 95% accuracy in patient group stratification using the corpus callosum centile widths.ConclusionFocal volume loss is seen in the corpus callosum of children with hypoxic–ischaemic brain injury secondary to loss of commissural fibres arising in the paracentral lobules. Support vector machine stratification into the hypoxic–ischaemic brain injury group or the control group on the basis of corpus callosum width is highly accurate and points towards rapid clinical translation of this technique as a potential biomarker of hypoxic–ischaemic brain injury.

Radiation Dose Reduction in 4D Cerebral CT Angiography by Individualized Estimation of Cerebral Circulation Time.

BACKGROUND AND PURPOSE: The novel technique of 4D CTA for dynamic assessment of the intracranial vessels has a greater radiation burden than conventional CTA. Previous descriptions of the technique used a fixed-duration exposure protocol. This study examines the potential for dose reduction by individualizing exposure time to patient physiology by the use of time-enhancement curve techniques as previously applied in CT angiography and venography. MATERIALS AND METHODS: 4D-CTA examinations performed at our institution were retrospectively reviewed. Scan protocols used a test-bolus scan with either a subjective estimate of the main acquisition timing (estimated-duration method) or a quantitative measure (measured-duration method). The estimated-duration method used peak arterial enhancement to determine the start of exposure, with the duration chosen at the radiologists discretion. The measured-duration method used arterial and venous time-enhancement curves to determine exposure start and duration. Exposure duration, study adequacy, quality score, and maximum venous enhancement were compared among groups. RESULTS: One hundred fifty-one examinations used the estimated-duration method, and 53 used measured-duration. The measured-duration method used a shorter exposure time (10 versus 15.8 seconds; P < .001). There was no statistically significant difference in the study adequacy rate, subjective quality score, or maximum venous enhancement. The radiation dose was reduced by 51% in the measured-duration method (3021 mGy × cm, 6.9 mSv, versus 1473 mGy × cm, 3.4 mSv). Both methods showed good agreement with DSA (κ = 0.88 for estimated-duration, κ = 1.0 for measured duration). CONCLUSIONS: Exposure time in 4D-CTA can be reduced with dual time-enhancement curves to match exposure to physiology without degrading study adequacy or quality.