Justin J. Cross

In Vivo Detection of Macrophages in Human Carotid Atheroma: Temporal Dependence of Ultrasmall Superparamagnetic Particles of Iron Oxide-Enhanced MRI

Background— It has been suggested that inflammatory cells within vulnerable plaques may be visualized by superpara-magnetic iron oxide particle–enhanced MRI. The purpose of this study was to determine the time course for macrophage visualization with in vivo contrast–enhanced MRI using an ultrasmall superparamagnetic iron oxide (USPIO) agent in symptomatic human carotid disease. Methods— Eight patients scheduled for carotid endarterectomy underwent multisequence MRI of the carotid bifurcation before and 24, 36, 48, and 72 hours after Sinerem (2.6 mg/kg) infusion. Results— USPIO particles accumulated in macrophages in 7 of 8 patients given Sinerem. Areas of signal intensity reduction, corresponding to USPIO/macrophage–positive histological sections, were visualized in all 7 of these patients, optimally between 24 and 36 hours, decreasing after 48 hours, but still evident up to 96 hours after infusion. Conclusions— USPIO-enhanced MRI of carotid atheroma can be used to identify macrophages in vivo. The temporal change in the resultant signal intensity reduction on MRI suggests an optimal time window for the detection of macrophages on postinfusion imaging.

Contrast-enhanced MR angiography for carotid disease Diagnostic and potential clinical impact

Objective: To compare contrast-enhanced MR angiography (CEMRA) with intra-arterial digital subtraction angiography (DSA) for evaluating carotid stenosis. Methods: A total of 167 consecutive symptomatic patients, scheduled for DSA following screening duplex ultrasound (DUS), were prospectively recruited to have CEMRA. Three independent readers reported on each examination in a blinded and random manner. Agreement was assessed using the Bland-Altman method. Diagnostic and potential clinical impact of CEMRA was evaluated, singly and in combination with DUS. Results: CEMRA tended to overestimate stenosis by a mean bias ranging from 2.4 to 3.8%. A significant part of the disagreement between CEMRA and DSA was directly caused by interobserver variability. For detection of severe stenosis, CEMRA alone had a sensitivity of 93.0% and specificity of 80.6%, with a diagnostic misclassification rate of 15.0% (n = 30). More importantly, clinical decision-making would, however, have been potentially altered only in 6.0% of cases (n = 12). The combination of concordant DUS and CEMRA reduced diagnostic misclassification rate to 10.1% (n = 19) at the expense of 47 (24.9%) discordant cases needing to proceed to DSA. An intermediate approach of selective DUS review resulted in a marginally worse diagnostic misclassification rate of 11.6% (n = 22) but with only 6.8% of discordant cases (n = 13). Conclusions: DSA remains the gold standard for carotid imaging. The clinical misclassification rate with CEMRA, however, is acceptably low to support its safe use instead of DSA. The appropriateness of combination strategies depends on institutional choice and cost-effectiveness issues.

Aetiological differences in neuroanatomy of the vegetative state: insights from diffusion tensor imaging and functional implications

Background An improved in vivo understanding of variations in neuropathology in the vegetative state (VS) may aid diagnosis, improve prognostication and help refine the selection of patients for particular treatment regimes. The authors have used diffusion tensor imaging (DTI) to characterise the extent and location of white matter loss in VS secondary to traumatic brain injury (TBI) and ischaemic–hypoxic injury. Methods Twelve patients with VS (seven TBI, five ischaemic/hypoxic injuries) underwent MRI including DTI at a minimum of 3 months postinjury. Mean apparent diffusion coefficient, fractional anisotropy and eigenvalues were obtained for whole-brain grey and white matter, the pons, thalamus, ventral midbrain, dorsal midbrain and the corpus callosum. DTI measures of supratentorial damage were compared with a summed measure from the JFK modified Coma Recovery Scale (CRS-R) and with a three-point scale of functional magnetic resonance imaging (fMRI) response to an auditory paradigm to assess whether residual integrity of supratentorial white matter connectivity correlated with cortical processing. Results Conventional radiological approaches did not detect lesions in regions where quantitative DTI demonstrated abnormalities. There was evidence of marked, broadly similar, abnormalities in the supratentorial grey- and white-matter compartments from both aetiologies. In contrast, discordant findings were found in the infratentorial compartment, with DTI abnormalities in the brainstem confined to the TBI group. Supratentorial DTI abnormalities correlated with the CRS-R as well as responses to an fMRI paradigm that detected convert cognitive processing. Conclusions DTI may help to characterise differences in patients in VS. These findings may have implications for response to therapies, and should be taken into account in trials of interventions aimed at arousal in VS.

Measuring carotid stenosis on contrast-enhanced magnetic resonance angiography: diagnostic performance and reproducibility of 3 different methods.

Background and Purpose— The aim of this study was to compare diagnostic performance and reproducibility of 3 different methods of quantifying stenosis on contrast-enhanced magnetic resonance angiography (CEMRA), with intra-arterial digital subtraction angiography (DSA) as the reference standard. Methods— 167 symptomatic patients scheduled for DSA, after screening Doppler ultrasound, were prospectively recruited to undergo CEMRA. Severity of stenosis was measured according to the North American Symptomatic Trial Collaborators (NASCET), European Carotid Surgery Trial (ECST), and the common carotid (CC) methods. Measurements for each method were made for 284 vessels (142 included patients) on both CEMRA and DSA in a blinded and randomized manner by 3 independent attending neuroradiologists. Results— Significant differences in prevalence of severe stenosis were seen with the 3 methods on both DSA and CEMRA, with ECST yielding the least and NASCET the most cases of severe stenosis. Overall, all 3 methods performed similarly well in terms of intermodality correlation and agreement. No significant differences in interobserver agreement were found on either modality. With CEMRA, however, we found a significantly lower sensitivity for detection of severe stenosis with ECST (79.8%) compared with NASCET (93.0%), with DSA as reference standard. Conclusions— Uniformity of carotid stenosis measurement methods is desirable because patient management may otherwise differ substantially. All 3 methods are adequate for use with DSA. With CEMRA, however, this study supports use of the NASCET method because of improved sensitivity for detecting severe stenosis.

Mapping Traumatic Axonal Injury Using Diffusion Tensor Imaging: Correlations with Functional Outcome

Background Traumatic brain injury is a major cause of morbidity and mortality worldwide. Ameliorating the neurocognitive and physical deficits that accompany traumatic brain injury would be of substantial benefit, but the mechanisms that underlie them are poorly characterized. This study aimed to use diffusion tensor imaging to relate clinical outcome to the burden of white matter injury. Methodology/Principal Findings Sixty-eight patients, categorized by the Glasgow Outcome Score, underwent magnetic resonance imaging at a median of 11.8 months (range 6.6 months to 3.7 years) years post injury. Control data were obtained from 36 age-matched healthy volunteers. Mean fractional anisotropy, apparent diffusion coefficient (ADC), and eigenvalues were obtained for regions of interest commonly affected in traumatic brain injury. In a subset of patients where conventional magnetic resonance imaging was completely normal, diffusion tensor imaging was able to detect clear abnormalities. Significant trends of increasing ADC with worse outcome were noted in all regions of interest. In the white matter regions of interest worse clinical outcome corresponded with significant trends of decreasing fractional anisotropy. Conclusions/Significance This study found that clinical outcome was related to the burden of white matter injury, quantified by diffusivity parameters late after traumatic brain injury. These differences were seen even in patients with the best outcomes and patients in whom conventional magnetic resonance imaging was normal, suggesting that diffusion tensor imaging can detect subtle injury missed by other techniques. An improved in vivo understanding of the pathology of traumatic brain injury, including its distribution and extent, may enhance outcome evaluation and help to provide a mechanistic basis for deficits that remain unexplained by other approaches.

Imaging the vertebral artery

Although conventional intraarterial digital subtraction angiography remains the gold standard method for imaging the vertebral artery, noninvasive modalities such as ultrasound, multislice computed tomographic angiography and magnetic resonance angiography are constantly improving and are playing an increasingly important role in diagnosing vertebral artery pathology in clinical practice. This paper reviews the current state of vertebral artery imaging from an evidence-based perspective. Normal anatomy, normal variants and a number of pathological entities such as vertebral atherosclerosis, arterial dissection, arteriovenous fistula, subclavian steal syndrome and vertebrobasilar dolichoectasia are discussed.

Scrotal trauma: a cause of testicular atrophy

Scrotal trauma is often mentioned as a cause of testicular atrophy yet there have been few studies documenting the effect of scrotal trauma on testicular size months or years following injury. We performed clinical and sonographic examinations in 10 patients who had suffered blunt scrotal trauma. A significant reduction in volume of the injured testis was observed in 5/10 cases at follow-up sonography. In two cases the affected testis was heterogeneous and colour flow Doppler examination showed reduced flow. In three cases the testis was homogeneous but reduced in volume and in the remaining five cases the affected testis appeared normal. We conclude that testicular atrophy is a sequel of scrotal trauma and occurred in 50% of patients in this study.

Contrast-enhanced MR angiography vs intra-arterial digital subtraction angiography for carotid imaging: activity-based cost analysis.

The aim of this study was to compare the costs of performing contrast-enhanced MR angiography (CE MRA) with intra-arterial digital subtraction angiography (DSA) for the evaluation of carotid atherosclerotic disease. Activity-based cost analysis was used to identify the costs of performing each procedure. The variable direct costs of performing CE MRA and DSA were determined in 20 patients by using detailed time and motion studies. All personnel directly involved in the cases were tracked to the nearest minute and all consumable items used were recorded. Moreover, procedure times were prospectively recorded for an additional 80 patients who underwent both DSA and CE MRA. The variable direct costs of bed usage in the angiography day-case unit, all direct fixed costs as well as indirect costs were assessed from hospital and departmental accounting records. Total costs for each procedure were calculated and compared using Wilcoxon signed-rank sum test. Mean aggregate costs were €721 for DSA and €306 for CE MRA, resulting in potential savings of €415 per patient (p<0.0001). On average, a DSA procedure thus cost approximately 2.4 (95% confidence intervals: 2.2–2.6) times more than CE MRA to our medical institution. Sensitivity analyses confirmed the robustness of our conclusions across wide ranges of plausible values for various parameters. Assuming equal diagnostic performance, institutions may have substantial cost savings if CE MRA is used instead of DSA for carotid imaging.

Current diagnostic approaches to subarachnoid haemorrhage

Over the past decade, significant advances have been made in the field of subarachnoid haemorrhage (SAH). Prompt diagnosis with high-resolution CT and intensive critical care support remain key aspects of good patient management. Early identification and definitive treatment of underlying ruptured aneurysms is generally advocated to reduce the risk of re-bleeding, a complication with high mortality and morbidity. Although intra-arterial digital subtraction angiography (DSA) is still considered the gold standard for sourcing aneurysms, CT angiography, especially with the evolution of multi-slice technology, is slowly gaining acceptance as a rapid, accessible and minimally invasive method which appears likely to replace DSA as first-line modality in the future. Furthermore, the advent of Guglielmi detachable coils and the ISAT trial have revolutionised the treatment of ruptured aneurysms, with a significant trend towards endovascular coiling away from operative clipping. Improvements in clinical experience, coiling technology and assistive devices now allow interventionalists to potentially treat the majority of aneurysms, including wide-necked or complex lesions. The uncertain long-term results of coiling, however, still fuel strong debate and controversy. This review summarises current diagnostic approaches to SAH from a radiological perspective, with an emphasis on aneurysmal SAH and an evidence-based approach to the role of imaging and interventional radiology in diagnosis, treatment and follow-up.

Gliomatosis peritonei associated with a ventriculo-peritoneal shunt.

Gliomatosis peritonei (GP) is defined as the implantation of mature glial tissue within the peritoneal cavity. It is a rare benign condition usually described in the setting of ovarian teratomas. It can also occur as a rare complication of ventriculoperitoneal (VP) shunts, when it is attributed to transport of glial tissue from the cerebrospinal fluid into the peritoneal cavity via the shunt. However, most cases have been described in young children, who present with inguinal hernias and with glial implants detected on microscopic analysis of their hernia sacs. We describe an unusual presentation of GP with a peritoneal mass and ascites in a 27-yearold woman with a history of posterior fossa surgery and VP shunt for treatment of medulloblastoma.