Using curve-fitting of curvilinear features for assessing registration of clinical neuropathology with in vivo MRI.

Traditional neuropathological examination provides information about neurological disease or injury of a patient at a high-resolution level. Correlating this type of post mortem diagnosis with in vivo image data of the same patient acquired by non-invasive tomographic scans greatly complements the interpretation of any disease or injury. We present the validation of a registration method for correlating macroscopic pathological images with MR images of the same patient. This also allows for 3-D mapping of the distribution of pathological changes throughout the brain. As the validation deals with datasets of widely differing sampling, we propose a method using smooth curvilinear anatomical features in the brain which allows interpolation between wide-spaced samples. Curvilinear features are common anatomically, and if selected carefully have the potential to allow determination of the accuracy of co-registration across large areas of a volume of interest.

A construction of an averaged representation of human cortical gyri using non-linear principal component analysis.

Because of the complex shape of human cortical gyri and great variation between individuals, development of effective representation schemes which allow establishment of correspondence between individuals, extraction of average structure of a population, and co-registration has proved very difficult. We introduce an approach which extracts line representations of gyri at different depths from high resolution MRI, labels main gyri semi-automatically, and extracts a template from a population using non-linear principal component analysis. The method has been tested on data from 96 healthy human volunteers. The model captures the most salient shape features of all major cortical gyri, and can be used for inter-subject registration, for investigating regionalized inter-subject variability, and for inter-hemispheric comparisons.

Integrating watersheds and critical point analysis for object detection in discrete 2D images.

This paper presents an improved method for the detection of "significant" low-level objects in medical images. The method overcomes topological problems where multiple redundant saddle points are detected in digital images. Information derived from watershed regions is used to select and refine saddle points in the discrete domain and to construct the watersheds and watercourses (ridges and valleys). We also demonstrate an improved method of pruning the tessellation by which to define low level objects in zero order images. The algorithm was applied on a set of medical images with promising results. Evaluation was based on theoretical analysis and human observer experiments.

Retrograde amnesia and the volume of critical brain structures.

There are many controversies concerning the structural basis of retrograde amnesia (RA). One view is that memories are held briefly within a medial temporal store ("hippocampal complex") before being "consolidated" or reorganised within temporal neocortex and/or networks more widely distributed within the cerebral cortex. An alternative view is that the medial temporal lobes are always involved in the storage and retrieval (reactivation) of autobiographical memories (multiple trace theory). The present study used quantitative magnetic resonance imaging (MRI) in 40 patients with focal pathology/volume loss in different sites, to examine the correlates of impairment on three different measures of RA. The findings supported the view that widespread neural networks are involved in the storage and retrieval of autobiographical and other remote memories. Brain volume measures in critical structures could account for 60% of variance on autobiographical memory measures (for incidents and facts) in diencephalic patients and for 60-68% of variance in patients with frontal lesions. Significant correlations with medial temporal lobe volume were found only in the diencephalic group, in whom they were thought to reflect thalamic changes, but not in patients with herpes encephalitis or hypoxia in whom the temporal lobes were particularly implicated. The latter finding fails to support one of the main predictions of multiple trace theory, as presently expounded.

Correlation of intra-operative duplex findings during carotid endarterectomy with neurological events and recurrent stenosis at one year.

OBJECTIVES: Carotid endarterectomy has been used to treat both asymptomatic and symptomatic disease and this has meant that recurrent stenosis and its effect on late stroke risk have become increasingly important. In this study we compared anatomical defects and residual stenosis identified intra-operatively with recurrent stenosis and new symptoms developing in the first year after surgery. DESIGN, MATERIALS & METHODS: Two hundred and forty-four consecutive patients undergoing carotid endarterectomy were studied prospectively. Residual anatomical defects were noted; residual stenosis was defined by intra-operative duplex ultrasound as >50%. New stenoses and clinical events during the one-year surveillance period were documented. RESULTS: There was an increased incidence of recurrent stenosis at one year in vessels with residual stenoses (p<0.001) and in vessels containing a residual anatomical defect (p=0.037). There was no significant difference in recurrent stenosis rate with respect to closure (primary or patch) or seniority of surgeon but recurrent stenosis was increased in females (p=0.026). The majority (70%) of restenotic lesions were localised to the origin of the internal carotid artery. The late stroke rate was 0.9% and was not related to recurrent stenosis or symptoms. CONCLUSIONS: Residual stenosis and intra-luminal defects at completion increase the recurrent stenosis rate at one year. The aetiology of recurrent stenosis is multi-factorial and further studies are required to determine whether it is justified to modify the criteria for re-exploration with a view to reducing recurrent stenosis.

MRI of Creutzfeldt-Jakob disease: imaging features and recommended MRI protocol.

Creutzfeldt-Jakob Disease (CJD) is a rare, progressive and invariably fatal neurodegenerative disease characterized by specific histopathological features. Of the four subtypes of CJD described, the commonest is sporadic CJD (sCJD). More recently, a new clinically distinct form of the disease affecting younger patients, known as variant CJD (vCJD), has been identified, and this has been causally linked to the bovine spongiform encephalopathy (BSE) agent in cattle. Characteristic appearances on magnetic resonance imaging (MRI) have been identified in several forms of CJD; sCJD may be associated with high signal changes in the putamen and caudate head and vCJD is usually associated with hyperintensity of the pulvinar (posterior nuclei) of the thalamus. These appearances and other imaging features are described in this article. Using appropriate clinical and radiological criteria and tailored imaging protocols, MRI plays an important part in the in vivodiagnosis of this disease.

Exploring the discrimination power of the time domain for segmentation and characterization of active lesions in serial MR data.

This paper presents a new method for the automatic segmentation and characterization of object changes in time series of three-dimensional data sets. The technique was inspired by procedures developed for analysis of functional MRI data sets. After precise registration of serial volume data sets to 4-D data, we applied a time series analysis taking into account the characteristic time function of variable lesions. The images were preprocessed with a correction of image field inhomogeneities and a normalization of the brightness over the whole time series. Thus, static regions remain unchanged over time, whereas changes in tissue characteristics produce typical intensity variations in the voxel's time series. A set of features was derived from the time series, expressing probabilities for membership to the sought structures. These multiple sources of uncertain evidence were combined to a single evidence value using Dempster-Shafer's theory. The project was driven by the objective of improving the segmentation and characterization of white matter lesions in serial MR data of multiple sclerosis patients. Pharmaceutical research and patient follow-up requires efficient and robust methods with a high degree of automation. The new approach replaces conventional segmentation of series of 3-D data sets by a 1-D processing of the temporal change at each voxel in the 4-D image data set. The new method has been applied to a total of 11 time series from different patient studies, covering time resolutions of 12 and 24 data sets over a period of about 1 year. The results demonstrate that time evolution is a highly sensitive feature for detection of fluctuating structures.

The pulvinar sign on magnetic resonance imaging in variant Creutzfeldt-Jakob disease.

BACKGROUND: There is a need for an accurate non-invasive diagnostic test for variant Creutzfeldt-Jakob disease (vCJD). We investigated the sensitivity and specificity of bilateral pulvinar high signal on magnetic resonance imaging (MRI) for the diagnosis of vCJD. METHODS: MRI from patients with vCJD and controls (patients with suspected CJD) were analysed. Scans were reviewed on two separate occasions by two neuroradiologists and scored for the distribution of changes, and likely final diagnosis. Scans from vCJD cases were reassessed to reach a consensus on all abnormalities. FINDINGS: We analysed 36 patients and 57 controls. vCJD patients were correctly identified based on bilateral pulvinar high signal in 29 of 36 and 32 of 36 cases on the first assessment by the two radiologists, and 32 of 36 and 31 of 36 on their second assessment. Bilateral increased pulvinar signal was identified in one of 57 and one of 57 controls on the first assessment and two of 57 and three of 57 controls on the second assessment. These reported changes in controls were graded as minimal/equivocal in six of seven patients and moderate in one (<0.5% of all control assessments). 80% of the assessments in vCJD cases were graded as moderate or substantial. On consensus review, 28 of 36 cases and none of 57 controls had prominent bilateral pulvinar signal-sensitivity 78% (95% CI 60-90%) and specificity 100% (95% CI 94-100%). Other common MRI features of vCJD were medial thalamic and periaqueductal grey matter high signal, and the notable absence of cerebral atrophy. Pulvinar high signal correlated with histological gliosis. INTERPRETATION: In the appropriate clinical context the MRI identification of bilaterally increased pulvinar signal is a useful non-invasive test for the diagnosis of vCJD.

Cost-effective carotid endarterectomy.

BACKGROUND: Although carotid endarterectomy is increasing in the UK, there is evidence that the procedure is still underused. Methods of reducing cost in a single vascular unit have been assessed using a continuous audit including outcome measures. METHODS: A consecutive series of 333 patients admitted over 7 years under a single consultant surgeon were studied. Outcome measures included the rate of perioperative neurological complication of any kind, and death. The length of hospital stay and the number of readmissions within 30 days were recorded prospectively by computerized audit. RESULTS: Over the interval of the study, the number of preoperative investigations was reduced; angiography and cerebral computed tomography were reserved for specific indications. The median duration of hospital stay decreased from 7 to 2 days. There was no change in the stroke and death rate (3 per cent) during the study and only two patients required readmission within 30 days. CONCLUSION: Carotid endarterectomy can be performed cost-effectively using non-invasive preoperative investigations for the majority of patients. In-hospital stay has been reduced and the routine use of intensive care replaced by a 2-h stay in theatre recovery. These changes have been achieved without compromising patient safety.

A geometry-and intensity-based partial volume correction for MRI volumetric studies.

Segmentation of objects of interest in magnetic resonance imaging is a necessary procedure for volumetric calculations. However, these direct measurements tend to be inaccurate due to the intrinsic MRI partial volume effects. In this paper, a general method for correcting these effects based on the geometry and grey level intensity of the segmented objects is presented. This method is independent of the segmentation strategy used to extract the objects of interest. An evaluation for three different segmentation methods is presented and it is shown that the proposed partial volume correction can improve the volume estimation of all three methods.

New variant Creutzfeldt-Jakob disease: neurological features and diagnostic tests.

BACKGROUND: In April, 1996, ten cases of Creutzfeldt-Jakob disease (CJD) with an apparently new clinicopathological phenotype were published and it was suggested that these new variant cases (nvCJD) might be causally linked to bovine spongiform encephalopathy (BSE). There have now been 21 cases of nvCJD in the UK and one case in France. We report clinical features and diagnostic test results of the first 14 cases of nvCJD in the UK. METHODS: Case ascertainment of CJD was mainly by direct referral from neurologists and neuropathologists. Clinical and investigate details were obtained by interview with patients' relatives and by examination of case notes. Ten cases in this report were examined while alive. Prion protein (PrP) gene analysis was carried out with informed consent from the patient or from a relative. The diagnosis of nvCJD was established histologically. FINDINGS: Eight cases were women. Mean age at onset of symptoms was 29 (16-48) years and the median duration of illness was 14 (9-35) months. All patients had early psychiatric symptoms, most often depression, and 13 were seen by a psychiatrist early in the clinical course. Eight patients developed early sensory symptoms which were persistent and often painful. Neurological signs, including ataxia and involuntary movements, developed in all cases and towards the end of the illness, most had akinetic mutism. The electroencephalogram was abnormal in most patients but typical periodic complexes of CJD were not seen in any case. Cerebral imaging was usually normal or showed non-specific abnormalities; in two cases magnetic-resonance imaging scans showed high signal in the thalamus. INTERPRETATION: Clinical features in these cases are similar and relatively distinct from other forms of CJD, suggesting that this is a new clinical phenotype consistent with a single strain of infectious agent. There is, however, some overlap with atypical cases of sporadic CJD, and the diagnosis of nvCJD remains dependent on neuropathological confirmation.

The measurement of internal carotid artery stenosis: comparison of duplex with digital subtraction angiography.

OBJECTIVES: To compare the subjective (eyeballed) method for measuring internal carotid artery (ICA) stenosis by non-selective intra-arterial digital subtraction angiography (IA-DSA) with objective and duplex methods. DESIGN: Retrospective study. MATERIALS AND METHODS: Fifty-three consecutive patients underwent IA-DSA prior to carotid endarterectomy providing 103 carotid angiograms. Objective assessment of ICA stenosis was by the North American Symptomatic Carotid Endarteectomy Trial (NASCET) criterion and the Carotid Stenosis Index (CSI). Duplex estimation of stenosis was derived from peak systolic and diastolic velocities in the ICA and common carotid artery (CCA). RESULTS: The coefficient of repeatability was poorest for NASCET stenosis estimates (40%), whilst the improved values for CSI (20%) were consistent with the lower variability recorded for measuring the CCA diameter. Correlation and agreement levels between subjective (r = 0.80, -41% to +33%) or objective assessments and duplex (NASCET: r = 0.76; -52 to +28%; CSI: r = 0.72; -27 to +39%) showed similar values. CONCLUSIONS: We conclude that the inter-observer variability for assessing angiograms obtained by arch injection is considerable and precludes high agreement when IA-DSA is compared with other methods. As the agreement of duplex ultrasound with IA-DSA is similar to the agreement between DSA methods, duplex can be offered as the first stage assessment of ICA stenosis, with the proviso that the duplex assessment is performed consistently by an experienced operator.

The changing indications for carotid endarterectomy in the UK.

In early series the majority of carotid endarterectomies were performed in patients with amaurosis fugax (AFx) or transient ischaemic attacks (TIAs) who were thought to have atheromatous ulcers of the carotid bifurcation or the internal carotid artery (ICA). The degree of stenosis was considered to be of secondary importance. We compared our own data with two British series undertaken in the early and late 80s/early 90s. This reflects the broadening of indications and the change of practice for carotid endarterectomy over the years, on the one hand towards including patients who are at greater risk of perioperative stroke (previous CVAs vs TIAs, crescendo TIAs and stroke in evolution), and on the other towards patients who have had no symptoms attributable to the carotid lesion (asymptomatic cases, combined carotid and cardiac procedures).

Morphological and hemodynamic assessments of carotid stenosis using quantitative digital subtraction angiography.

BACKGROUND AND PURPOSE: Digital angiography is the best established tool for assessing atheromatous disease of extracranial blood vessels. Advances in computer technology have now made it possible and practicable to extract quantitative information (length, width, cross-sectional area, and flow velocity) from good-quality clinical angiograms, allowing calculation of volume flow and pressure gradient. The technique of quantitative angiography (QA) is used for assessing coronary artery disease, but to date there has been no clinical application in patients with cerebrovascular disease. SUMMARY OF REPORT: We have developed a computer program for off-line analysis of routine digital subtraction angiographic images. From biplanar images, the program reconstructs the angiogram in three dimensions and performs quantitative analysis of each vessel. From this data, the pressure drop from the aortic arch to the circle of Willis is then calculated. We assessed the clinical applicability of QA in five patients investigated for transient ischemic attack. The carotid artery ipsilateral to the symptomatic hemisphere was occluded in one patient and had minor plaque in another. In the remaining three patients, ipsilateral internal carotid artery stenosis was measured by QA as producing area reductions of 55%, 72%, and 88% (equivalent to diameter reductions of 33%, 48%, and 65%, respectively). In these patients, the quantitative stenosis pressure gradients were calculated as 1.2, 3.0, and 3.5 mm Hg. respectively. Further calculation showed that each stenosis contributed to 18%, 24%, and 60%, respectively, of the total carotid pressure gradient from the aortic arch to the circle of Willis. These carotid arteries carried 47%, 42%, and 26%, respectively, of the total cerebral flow. The results of quantitative analysis were validated by comparing, within each patient, the differences in pressure gradients between right and left carotid systems of between right and left vertebral arteries (overall mean difference in pressure gradient, 0.6 +/- 0.5 mm Hg: P = NS). Finally, comparison was made of pressure gradients across the circle of Willis between the carotid and vertebrobasilar circulations (mean difference in pressure gradient, 4.1 +/- 5.3 mm Hg; P = NS). CONCLUSIONS: Quantitative angiography allows determination of the hemodynamic parameters of a vessel or stenosis. It has significant potential, both as a research tool and in routine clinical practice, for the investigation of cerebrovascular disease.

Development and preliminary evaluation of VISLAN, a surgical planning and guidance system using intra-operative video imaging.

VISLAN is an integrated neurosurgical planning and guidance system. New segmentation and rendering techniques have been incorporated. A stereo video system is used intra-operatively and fulfils four roles. First, the video display is overlaid with graphical outlines showing the position of the planned craniotomy or the target (enhanced reality displays). Second, a skin surface patch is reconstructed from the stereo video images using patterned light (mean errors of surface point location are < 0.15 mm). Third, a freely mobile, hand-held localizer is tracked in real time (position errors are < 0.5 mm and with improved calibration < 0.2 mm), with its position superimposed on the pre-operative patient representation to assist surgical guidance. Fourth, markers fixed to the skull bone next to the cranial opening are used to detect intra-operative movement and to update registration. Initial results from phantom experiments show an overall system accuracy of better than 0.9 mm for intra-operative localization of features defined in pre-operative images. The prototype system has been tested during six neurosurgical operations with very good results.

Validation of volume blood flow measurements using three-dimensional distance-concentration functions derived from digital x-ray angiograms.

RATIONALE AND OBJECTIVES: The authors present phantom validation of a method for computing pulsatile flow waveforms in arterial vessels from high-frame-rate biplane x-ray angiograms. METHODS: The three-dimensional course of a blood vessel is constructed from biplane digital x-ray angiograms. A parametric image of contrast mass versus time and true three-dimensional path length is generated. Adjacent contrast mass-distance profiles are matched to compute instantaneous velocity, which is multiplied by cross-sectional area to yield volume flow. An electromagnetic flowmeter was used to validate flow estimates in a phantom consisting of 150-mm tubes 3, 4, and 6 mm in diameter, orientated 15 degrees, 30 degrees, and 35 degrees to the imaging plane, with flow rates and waveforms expected in vivo. RESULTS: Mean and peak flows were accurate to within 9% and 10%, respectively, for velocities of less than 1 meter/second at a frame rate of 25 frames per second. CONCLUSIONS: A practical method for computing highly pulsatile flow waveforms in vivo in tortuous vessels is presented.

Measurement of liver blood flow: a review.

The study of hepatic haemodynamics is of importance in understanding both hepatic physiology and disease processes as well as assessing the effects of portosystemic shunting and liver transplantation. The liver has the most complicated circulation of any organ and many physiological and pathological processes can affect it. This review surveys the methods available for assessing liver blood flow, examines the different parameters being measured and outlines problems of applicability and interpretation for each technique. The classification of these techniques is to some extent arbitrary and several so called "different" methods may share certain common principles. The methods reviewed have been classified into two groups (Table 1): those primarily reflecting flow through discrete vessels or to the whole organ and those used to assess local microcirculatory blood flow. All techniques have their advantages and disadvantages and in some situations a combination may provide the most information. In addition, because of the many factors affecting liver blood flow and sinusoidal perfusion, readings in a single subject may vary depending on positioning, recent food intake, anxiety, anaesthesia and drug therapy. This must be borne in mind if different studies are to be meaningfully compared.