Successful treatment of residual pituitary adenoma in persistent acromegaly following localisation by 11C-methionine PET co-registered with MRI.

OBJECTIVE: To determine if functional imaging using 11C-methionine positron emission tomography co-registered with 3D gradient echo MRI (Met-PET/MRI), can identify sites of residual active tumour in treated acromegaly, and discriminate these from post-treatment change, to allow further targeted treatment. DESIGN/METHODS: Twenty-six patients with persistent acromegaly after previous treatment, in whom MRI appearances were considered indeterminate, were referred to our centre for further evaluation over a 4.5-year period. Met-PET/MRI was performed in each case, and findings were used to decide regarding adjunctive therapy. Four patients with clinical and biochemical remission after transsphenoidal surgery (TSS), but in whom residual tumour was suspected on post-operative MRI, were also studied. RESULTS: Met-PET/MRI demonstrated tracer uptake only within the normal gland in the four patients who had achieved complete remission after primary surgery. In contrast, in 26 patients with active acromegaly, Met-PET/MRI localised sites of abnormal tracer uptake in all but one case. Based on these findings, fourteen subjects underwent endoscopic TSS, leading to a marked improvement in (n = 7), or complete resolution of (n = 7), residual acromegaly. One patient received stereotactic radiosurgery and two patients with cavernous sinus invasion were treated with image-guided fractionated radiotherapy, with good disease control. Three subjects await further intervention. Five patients chose to receive adjunctive medical therapy. Only one patient developed additional pituitary deficits after Met-PET/MRI-guided TSS. CONCLUSIONS: In patients with persistent acromegaly after primary therapy, Met-PET/MRI can help identify the site(s) of residual pituitary adenoma when MRI appearances are inconclusive and direct further targeted intervention (surgery or radiotherapy).

A role for 11C-methionine PET imaging in ACTH-dependent Cushing's syndrome.

OBJECTIVE: We report our experience of functional imaging with (11)C-methionine positron emission tomography-computed tomography (PET-CT) co-registered with 3D gradient echo (spoiled gradient recalled (SPGR)) magnetic resonance imaging (MRI) in the investigation of ACTH-dependent Cushing's syndrome. DESIGN: Twenty patients with i) de novo Cushing's disease (CD, n=10), ii) residual or recurrent hypercortisolism following first pituitary surgery (±radiotherapy; n=8) or iii) ectopic Cushing's syndrome (n=2) were referred to our centre for functional imaging studies between 2010 and 2015. Six of the patients with de novo CD and five of those with persistent/relapsed disease had a suspected abnormality on conventional MRI. METHODS: All patients underwent (11)C-methionine PET-CT. For pituitary imaging, co-registration of PET-CT images with contemporaneous SPGR MRI (1 mm slice thickness) was performed, followed by detailed mapping of (11)C-methionine uptake across the sella in three planes (coronal, sagittal and axial). This allowed us to determine whether suspected adenomas seen on structural imaging exhibited focal tracer uptake on functional imaging. RESULTS: In seven of ten patients with de novo CD, asymmetric (11)C-methionine uptake was observed within the sella, which co-localized with the suspected site of a corticotroph microadenoma visualised on SPGR MRI (and which was subsequently confirmed histologically following successful transsphenoidal surgery (TSS)). Focal (11)C-methionine uptake that correlated with a suspected abnormality on pituitary MRI was seen in five of eight patients with residual or recurrent Cushing's syndrome following first TSS (and pituitary radiotherapy in two cases). Two patients elected to undergo repeat TSS with histology confirming a corticotroph tumour in each case. In two patients with the ectopic ACTH syndrome, (11)C-methionine was concentrated in sites of distant metastases, with minimal uptake in the sellar region. CONCLUSIONS: (11)C-methionine PET-CT can aid the detection of ACTH-secreting tumours in Cushing's syndrome and facilitate targeted therapy.

The genome of the sparganosis tapeworm Spirometra erinaceieuropaei isolated from the biopsy of a migrating brain lesion.

BACKGROUND: Sparganosis is an infection with a larval Diphyllobothriidea tapeworm. From a rare cerebral case presented at a clinic in the UK, DNA was recovered from a biopsy sample and used to determine the causative species as Spirometra erinaceieuropaei through sequencing of the cox1 gene. From the same DNA, we have produced a draft genome, the first of its kind for this species, and used it to perform a comparative genomics analysis and to investigate known and potential tapeworm drug targets in this tapeworm. RESULTS: The 1.26 Gb draft genome of S. erinaceieuropaei is currently the largest reported for any flatworm. Through investigation of ß-tubulin genes, we predict that S. erinaceieuropaei larvae are insensitive to the tapeworm drug albendazole. We find that many putative tapeworm drug targets are also present in S. erinaceieuropaei, allowing possible cross application of new drugs. In comparison to other sequenced tapeworm species we observe expansion of protease classes, and of Kuntiz-type protease inhibitors. Expanded gene families in this tapeworm also include those that are involved in processes that add post-translational diversity to the protein landscape, intracellular transport, transcriptional regulation and detoxification. CONCLUSIONS: The S. erinaceieuropaei genome begins to give us insight into an order of tapeworms previously uncharacterized at the genome-wide level. From a single clinical case we have begun to sketch a picture of the characteristics of these organisms. Finally, our work represents a significant technological achievement as we present a draft genome sequence of a rare tapeworm, and from a small amount of starting material.

Recovery of oculomotor nerve palsy secondary to posterior communicating artery aneurysms.

BACKGROUND: Recent studies suggest more favourable recovery of oculomotor nerve palsy (ONP) caused by posterior communicating artery (PComA) aneurysms with microsurgical clipping compared to endovascular coiling. We describe a consecutive series of patients with ONP from PComA aneurysms treated by microsurgical clipping or endovascular coiling. METHODS: We retrospectively reviewed medical records of all patients from 2005 to 2009 with complete or partial ONP from PComA aneurysms. RESULTS: Twenty patients were identified, three with unruptured aneurysms. Two patients with ruptured aneurysms were unfit for treatment and therefore excluded. Of the 18 patients included (15 female), 9 underwent microsurgical clipping and 9 received endovascular coiling. Patients treated by surgical clipping were significantly younger compared to those treated by endovascular coiling (mean 52.3 vs. 67.9 years; p = 0.039). Five patients had incomplete ONP (3 clipped, 2 coiled) and thirteen had complete ONP. At 6 months, six of nine patients treated with clipping and five of nine patients treated with coiling had complete resolution of their ONP (p = 1.0); the remainder had partial improvement. There was no significant difference in duration of pre-treatment ONP, age, sex or status of aneurysm (ruptured or unruptured) between patients in the two groups or between those with full or partial recovery. However, all 5 patients with incomplete ONP at presentation recovered fully, compared with 6 of 13 patients who presented with complete ONP. CONCLUSIONS: We found no significant difference between clipping and coiling in the recovery of ONP due to PComA aneurysms. Patient who present with incomplete ONP are more likely to have a full recovery of ONP following either treatment modality than those who present with complete ONP.

A comprehensive study of clinical, biochemical, radiological, vascular, cardiac, and sleep parameters in an unselected cohort of patients with acromegaly undergoing presurgical somatostatin receptor ligand therapy.

CONTEXT: Attainment of safe GH and IGF-1 levels is a central goal of acromegaly management. OBJECTIVE: The aim of this study was to determine the extent to which reductions in GH and IGF-1 concentrations correlate with amelioration of radiological, metabolic, vascular, cardiac, and respiratory sequelae in a single unselected patient cohort. STUDY DESIGN: This was a prospective, within-subject comparison in 30 patients with newly diagnosed acromegaly (15 women and 15 men: mean age, 54.3 years; range, 23-78 years) before and after 24 weeks of lanreotide Autogel (ATG) therapy. RESULTS: Reductions in GH and IGF-1 concentrations and tumor volume were observed in all but 2 patients (median changes [Δ]: GH, -6.88 µg/L [interquartile range -16.78 to -3.32, P = .000001]; IGF-1, -1.95 × upper limit of normal [-3.06 to -1.12, P = .000002]; and pituitary tumor volume, -256 mm(3) [-558 to -72.5, P = .0002]). However, apnea/hypopnea index scores showed highly variable responses (P = .11), which were independent of ΔGH or ΔIGF-1, but moderately correlated with Δweight (R(2) = 0.42, P = .0001). Although systolic (P = .33) and diastolic (P = .76) blood pressure were unchanged, improvements in arterial stiffness (aortic pulse wave velocity, -0.4 m/s [-1.2 to +0.2, P = .046]) and endothelial function (flow mediated dilatation, +1.73% [-0.32 to +6.19, P = .0013]) were observed. Left ventricular mass index regressed in men (-11.8 g/cm(2) [-26.6 to -1.75], P = .019) but not in women (P = .98). Vascular and cardiac changes were independent of ΔGH or ΔIGF-1 and also showed considerable interindividual variation. Metabolic parameters were largely unchanged. CONCLUSIONS: Presurgical ATG therapy lowers GH and IGF-1 concentrations, induces tumor shrinkage, and ameliorates/reverses cardiac, vascular, and sleep complications in many patients with acromegaly. However, responses vary considerably between individuals, and attainment of biochemical control cannot be assumed to equate to universal complication control.

Eyelid apraxia associated with bilateral paramedian thalamic infarct.

We report a case of bilateral thalamic infarct associated with bilateral eyelid apraxia. This extremely rare condition provides us with an opportunity to map clinical and neuroimaging findings to help better understand brain function.

High grade glioma: imaging combined with pathological grade defines management and predicts prognosis.

INTRODUCTION: There is ambiguity in pathological grading of high grade gliomas within the WHO 2000 classification, especially those with predominant oligodendroglial differentiation. PATIENTS AND METHODS: All adult high grade gliomas treated radically, 1996-2005, were assessed. Cases in which pathology was grade III but radiology suggested glioblastoma (GBM) were classified as 'grade III/IV'; their pathology was reviewed. RESULTS: Data from 245 patients (52 grade III, 18 grade III/IV, 175 GBM) were analysed using a Cox Proportional Hazards model. On pathology review, features suggestive of more aggressive behaviour were found in all 18 grade III/IV tumours. Oligodendroglial components with both necrosis and microvascular proliferation were present in 7. MIB-1 counts for the last 8 were all above 14%, mean 27%. Median survivals were: grade III 34 months, grade III/IV 10 months, GBM 11 months. Survival was not significantly different between grade III/IV and GBM. Patients with grade III/IV tumours had significantly worse outcome than grade III, with a hazard of death 3.7 times higher. CONCLUSIONS: The results highlight the current inconsistency in pathological grading of high grade tumours, especially those with oligodendroglial elements. Patients with histological grade III tumours but radiological appearances suggestive of GBM should be managed as glioblastoma.

Internal carotid artery stenosis: accuracy of subjective visual impression for evaluation with digital subtraction angiography and contrast-enhanced MR angiography.

PURPOSE: To prospectively determine, for both digital subtraction angiography (DSA) and contrast material-enhanced magnetic resonance (MR) angiography, the accuracy of subjective visual impression (SVI) in the evaluation of internal carotid artery (ICA) stenosis, with objective caliper measurements serving as the reference standard. MATERIALS AND METHODS: Local ethics committee approval and written informed patient consent were obtained. A total of 142 symptomatic patients (41 women, 101 men; mean age, 70 years; age range, 44-89 years) suspected of having ICA stenosis on the basis of Doppler ultrasonographic findings underwent both DSA and contrast-enhanced MR angiography. With each modality, three independent neuroradiologists who were blinded to other test results first visually estimated and subsequently objectively measured stenoses. Diagnostic accuracy and percentage misclassification for correct categorization of 70%-99% stenosis were calculated for SVI, with objective measurements serving as the reference standard. Interobserver variability was determined with kappa statistics. RESULTS: After exclusion of arteries that were unsuitable for measurement, 180 vessels remained for analysis with DSA and 159 vessels remained for analysis with contrast-enhanced MR angiography. With respect to 70%-99% stenosis, SVI was associated with average misclassification of 8.9% for DSA (8.9%, 7.8%, and 10.0% for readers A, B, and C, respectively) and of 11.7% for contrast-enhanced MR angiography (11.3%, 8.8%, and 15.1% for readers A, B, and C, respectively). Negative predictive values were excellent (92.3%-100%). Interobserver variability was higher for SVI (DSA, kappa = 0.62-0.71; contrast-enhanced MR angiography, kappa = 0.57-0.69) than for objective measurements (DSA, kappa = 0.75-0.80; contrast-enhanced MR angiography, kappa = 0.66-0.72). CONCLUSION: SVI alone is not recommended for evaluation of ICA stenosis with both DSA and contrast-enhanced MR angiography. SVI may be acceptable as an initial screening tool to exclude the presence of 70%-99% stenosis, but caliper measurements are warranted to confirm the presence of such stenosis.

Stroke attributable to a calcific embolus from the brachiocephalic trunk.

BACKGROUND AND PURPOSE: Calcific brain embolization is a rare event that is usually secondary to cardiac valve calcification. We present a case of stroke caused by embolization of calcific material from the brachiocephalic trunk, probably induced by radiotherapy. SUMMARY OF CASE: A 56-year-old right-handed female developed left-sided hemiparesis, hemihypesthesia, and sensory inattention. She had a history of right breast carcinoma that was excised 8 years previously followed by radiotherapy. She had no other history of note. Computed tomography of the head and magnetic resonance imaging confirmed a calcific embolus in right middle cerebral artery and an acute infarction in the corresponding territory. Plain chest radiography, carotid ultrasonography, transthoracic and transoesophageal echocardiography failed to demonstrate the source of calcific embolism. Computed tomography of the thorax revealed heavy calcification of the brachiocephalic trunk and the origin of the right common carotid artery. CONCLUSIONS: Undertaking a vigilant systematic search for the source in cases of calcific embolization is necessary. The aorta and its main branches are possible, yet unusual, sources of calcific emboli that merit investigation.

Cost-effectiveness of diagnostic strategies prior to carotid endarterectomy.

The main objective of this study was to assess the long-term cost-effectiveness of five alternative diagnostic strategies for identification of severe carotid stenosis in recently symptomatic patients. A decision-analytical model with Markov transition states was constructed. Data sources included a prospective study involving 167 patients who had screening Doppler ultrasound (DUS), confirmatory contrast-enhanced magnetic resonance angiography (CEMRA) and confirmatory digital subtraction angiography (DSA), individual patient data from the European Carotid Surgery Trial and other published clinical and cost data. A "selective" strategy, whereby all patients receive DUS and CEMRA (only proceeding to DSA if the CEMRA is positive and the DUS is negative), was most cost-effective. This was both the cheapest imaging and treatment strategy (35,205 dollars per patient) and yielded 6.1590 quality-adjusted life years (QALYs), higher than three alternative imaging strategies. Probabilistic sensitivity analysis demonstrated that there was less than a 10% probability that imaging with either DUS or DSA alone are cost-effective at the conventional 50,000 dollars/QALY threshold. In conclusion, DSA is not cost-effective in the routine diagnostic workup of most patients. DUS, with additional imaging in the form of CEMRA, is recommended, with a strategy of "CEMRA and selective DUS review" being shown to be the optimal imaging strategy.

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.

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.

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.

Evaluation of carotid stenosis with axial high-resolution black-blood MR imaging.

High-resolution axial black-blood MR imaging (BB MRI) has been shown to be able to characterise carotid plaque morphology. The aim of this study was to explore the accuracy of this technique in quantifying the severity of carotid stenosis. A prospective study of 54 patients with symptomatic carotid disease was conducted, comparing BB MRI to the gold standard, conventional digital subtraction X-ray angiography (DSA). The BB MRI sequence was a fast-spin echo acquisition (TE = 42 ms, ETL = 24, field of view = 100 x 100 mm, slice thickness = 3.0 mm) at 1.5 T using a custom-built phased-array coil. Linear measurements of luminal and outer carotid wall diameter were made directly from the axial BB MRI slices by three independent blinded readers and stenosis was calculated according to European Carotid Surgery Trial (ECST) criteria. There was good agreement between BB MRI and DSA (intraclass correlation = 0.83). Inter-observer agreement was good (average kappa = 0.77). BB MRI was accurate for detection of severe stenosis (> or = 80%) with sensitivity and specificity of 87 and 81%, respectively. Eight cases of "DSA-defined" moderate stenosis were overestimated as severe by BB MRI and this may be related to non-circular lumens. Axial imaging with BB MRI could potentially be used to provide useful information about severity of carotid stenosis.

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 Euro 721 for DSA and Euro 306 for CE MRA, resulting in potential savings of Euro 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.