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N C Fox

Publications and source records attributed to N C Fox.

At least 55 records · Page 3Linked to original sources
PubMed2001

Automated hippocampal segmentation by regional fluid registration of serial MRI: validation and application in Alzheimer's disease.

The application of voxel-level three-dimensional registration to serial magnetic resonance imaging (MRI) is described. This fluid registration determines deformation fields modeling brain change, which are consistent with a model describing a viscous fluid. The objective was to validate the measurement of hippocampal volumetric change by fluid registration in Alzheimer's disease (AD) against current methodologies. The hippocampus was chosen for this study because it is difficult to measure reproducibly by manual segmentation and is widely studied; however, the technique is applicable to any structure which can be delineated on a scan. First, suitable values for the viscosity-body-force-ratio, alpha (0.01), and the number of iterations (300), were established and the convergence, repeatability, linearity, and accuracy investigated and compared with expert manual segmentation. A simple model of hippocampal atrophy was used to compare simulated volumetric change against that obtained by fluid registration. Finally the serial segmentation was compared with the current gold standard technique-expert human labeling with a volume repeatability of approximately 4%-in 27 subjects (15 normal controls, 12 clinically diagnosed with Alzheimer's disease). The scan-rescan volumetric consistency of serial segmentation by fluid-registration was shown to be superior to human serial segmentors ( approximately 2%). The mean absolute volume difference between fluid and manual segmentation was 0.7%. Fluid registration has potential importance for tracking longitudinal structural changes in brain particularly in the context of the clinical trial where large numbers of subjects may have multiple MR scans.

Aged↗
PubMed2001

Haemodialysis and cerebral oedema.

BACKGROUND: Haemodialysis may cause neurological symptoms ranging from inconvenient feelings of disequilibrium to life-threatening neurological complications. There are animal data to suggest cerebral swelling may accompany haemodialysis and contribute symptomatically to dialysis disequilibrium. However, MR images acquired following haemodialysis often fail to demonstrate evidence of cerebral oedema. We wished to quantify any potential cerebral volume change which is caused by haemodialysis treatment. METHOD: Five renal patients and 5 control subjects had a two volumetric T1-weighted MRI scans on the same day. The patients were imaged immediately before and after haemodialysis. None were taking steroids. Precise positional matching (registration) was used to quantify cerebral volume change. RESULTS: Patients had an increase in cerebral volume following dialysis which averaged 32.8 ml (SE 7.4 ml, 3% brain volume). The change in the controls was 1.4 ml (SE 0.6 ml), p < 0.001. No patient had significant neurological symptoms. CONCLUSION: Cerebral oedema developed in the patients following dialysis. There is a good biological model for these observations. Modifications to dialysis may help. Common problems which increase cerebral volume, e.g. acute stroke, require careful appraisal in these patients. These observations need consideration when quantifying atrophy in dialysis patients.

Adult↗
PubMed2001

Patterns of temporal lobe atrophy in semantic dementia and Alzheimer's disease.

Volumetric magnetic resonance imaging analyses of 30 subjects were undertaken to quantify the global and temporal lobe atrophy in semantic dementia and Alzheimer's disease. Three groups of 10 subjects were studied: semantic dementia patients, Alzheimer's disease patients, and control subjects. The temporal lobe structures measured were the amygdala, hippocampus, entorhinal cortex, parahippocampal gyrus, fusiform gyrus, and superior, middle, and inferior temporal gyri. Semantic dementia and Alzheimer's disease groups did not differ significantly on global atrophy measures. In semantic dementia, there was asymmetrical temporal lobe atrophy, with greater left-sided damage. There was an anteroposterior gradient in the distribution of temporal lobe atrophy, with more marked atrophy anteriorly. All left anterior temporal lobe structures were affected in semantic dementia, with the entorhinal cortex, amygdala, middle and inferior temporal gyri, and fusiform gyrus the most severely damaged. Asymmetrical, predominantly anterior hippocampal atrophy was also present. In Alzheimer's disease, there was symmetrical atrophy of the entorhinal cortex, hippocampus, and amygdala, with no evidence of an anteroposterior gradient in the distribution of temporal lobe or hippocampal atrophy. These data demonstrate that there is a marked difference in the distribution of temporal lobe atrophy in semantic dementia and Alzheimer's disease. In addition, the pattern of atrophy in semantic dementia suggests that semantic memory is subserved by anterior temporal lobe structures, within which the middle and inferior temporal gyri may play a key role.

Aged↗
PubMed2001

Normalization of cerebral volumes by use of intracranial volume: implications for longitudinal quantitative MR imaging.

BACKGROUND AND PURPOSE: MR-based volumetric measures of cerebral structures are increasingly used for diagnostic purposes and to measure progression of atrophy. Variations in individual head size may be corrected by normalization with use of a total intracranial volume (TIV) measurement. The TIV also may be used to correct for voxel size fluctuations in serial studies. The TIV should be measured from the same images used for structural volumetry, usually T1-weighted imaging. The objectives were to show that normalization with TIV reduces interindividual variation, to develop and validate a simple protocol for measuring TIV from T1-weighted MR images, and to apply TIV normalization to serial brain measures in controls and subjects with Alzheimer disease (AD). METHODS: We measured TIV with a semiautomated segmentation technique on T1- and T2-weighted MR images in 55 controls, 10 AD patients, and two persons at risk of familial AD. Whole-brain volumes also were measured and normalized with TIVs. RESULTS: The TIV normalization of cross-sectional brain volumes significantly reduced interindividual variation; the coefficient of variation (CV) was reduced from 10.0% to 6.0% in controls (P <.001). The TIVs measured on T1-weighted images had low variability (CV, 0.16%) and did not differ significantly from those measured on T2-weighted images (P =.16). The TIV normalization of serial brain-volume measurements reduced interimage differences caused by voxel-scaling variations (CV reduced from 1.3% to 0.5%, P =.002) in 10 controls and five AD patients. CONCLUSION: Structural volumes should be normalized with a TIV, measured cross-sectionally, to reduce interindividual variation, and longitudinally with a concurrent measurement, to reduce subtle interimage differences. This may have important implications in progression studies.

Adult↗
PubMed2000

Detection of ventricular enlargement in patients at the earliest clinical stage of MS.

The aim of this study was to determine whether atrophy could be detected at the earliest clinical stages of MS. Patients were selected from a 1-year follow-up MRI study of clinically isolated syndromes. Nine patients who developed MS were compared with eight matched patients who had no further symptoms. Significant ventricular enlargement occurred in the group that developed MS but not in the other group. Our findings show that atrophy, albeit mild, can be detected early in the course of MS.

Adolescent↗
PubMed2000

Progressive cerebral atrophy in MS: a serial study using registered, volumetric MRI.

OBJECTIVE: To assess the potential of registered volumetric MRI in measuring rates of atrophy in MS. BACKGROUND: Pathologic and imaging studies suggest that the development of permanent neurologic impairment in MS is associated with progressive brain and spinal cord atrophy. Atrophy has been suggested as a potential marker of disease progression. Conventional atrophy measurements requiring manual outlining are time-consuming and subject to reproducibility problems. Registration of serial MRI may offer a useful alternative in that cerebral losses may be measured directly from automated subtraction of brain volumes. METHODS: Twenty-six patients with MS and 26 age- and gender-matched controls had two volumetric brain MR studies 1 year apart. Baseline brain and ventricular volumes were measured using semiautomated techniques, and follow-up scans were registered to baseline. Rates of cerebral atrophy were calculated directly from the registered scans. RESULTS: Baseline brain volumes in the MS group were smaller (mean difference 78 mL [95% CI 13 to 143; p = 0.02]) and ventricular volumes greater (mean difference 12 mL [95% CI 6 to 18; p < 0.001]) than controls. The rate of cerebral atrophy in the MS group (0.8% per year) was over twice that of controls (0.3%), and the rate of ventricular enlargement was five times greater than the controls (1.6 versus 0.3 mL/year). CONCLUSION: Progressive cerebral atrophy is an important feature of MS. Registration-based measurements are sensitive and reproducible, allowing progressive atrophy to be detected within 1 year and may have potential as a marker of progression in monitoring therapeutic trials.

Adult↗
PubMed2000

Intracranial volume and Alzheimer disease: evidence against the cerebral reserve hypothesis.

BACKGROUND: Total intracranial volume (TIV) measurement commonly is used to correct for variations in premorbid brain size in imaging studies of cerebral structures in Alzheimer disease (AD). This assumes no intrinsic difference in TIV between patients and control subjects and that TIV measurements are unaffected by cerebral atrophy. However, an autopsy study has suggested that a larger premorbid brain may protect against AD onset. A recent computed tomographic study lent support to this by finding a correlation between intracranial size and age at onset of AD in women. OBJECTIVE: To investigate the relationship between TIV and sporadic and familial AD. DESIGN: Retrospective case study. SETTING: Specialist dementia clinic. PATIENTS: Eighty-five patients with AD and 52 healthy volunteers. MAIN OUTCOME MEASURES: Age at symptom onset and TIV measured using a semiautomatic interactive thresholding technique on magnetic resonance imaging spanning the entire intracranial cavity. RESULTS: Reproducibility measurement was high (intrarater coefficient of variation, 1.2%; interrater coefficient of variation, 0.7%). Unlike brain atrophy in the patients with AD, TIV did not vary over time. Mean TIV did not differ significantly between any of the subject groups. There was no association between TIV and age or age at symptom onset. The only significant predictor of TIV was sex. CONCLUSIONS: Measurements of TIV are independent of atrophy and can be used safely to adjust for differences in head size in studies of cerebral structure in AD. Premorbid brain size does not differ between patients with familial and sporadic AD and controls and does not delay disease onset.

Adult↗
PubMed2000

Using serial registered brain magnetic resonance imaging to measure disease progression in Alzheimer disease: power calculations and estimates of sample size to detect treatment effects.

OBJECTIVE: To evaluate the rate of brain atrophy calculated from serial magnetic resonance imaging (MRI) registration as a surrogate marker of disease progression for use in clinical trials in Alzheimer disease (AD). METHODS: Eighteen patients with mild to moderate AD and 18 age-matched normal controls underwent 2 MRI brain scans separated by a 12-month interval. Each individual's later scan was registered to their first scan, and the volume of cerebral tissue loss calculated directly from the registered and subtracted MRI scan pairs. The mean and SD of the rate of brain volume changes were used to estimate the sample sizes that would be needed in a clinical trial with a drug anticipated to modify disease progression by varying degrees. Comparable sample size estimates were performed with data for other methods of monitoring rates of brain atrophy, extracted from published papers. RESULTS: The mean (SD) rate of brain atrophy for the patients with AD was 2.37% (1.11%) per year, while in the control group it was 0.41% (0.47%) per year. Based on these figures, to have 90% power to detect a drug effect equivalent to a 20% reduction in the rate of atrophy, 207 patients would be needed in each treatment arm. This assumes a 1-year placebo-controlled trial with a 10% patient dropout rate, and that 10% of scan pairs are unusable. CONCLUSION: Registration of serial MRI volume images provides a powerful method of quantification of brain atrophy that can be used to monitor progression of AD in clinical trials.

Aged↗
PubMed2000

Alzheimer's disease due to an intronic presenilin-1 (PSEN1 intron 4) mutation: A clinicopathological study.

We describe 21 affected individuals from a kindred with early-onset autosomal dominant familial Alzheimer's disease caused by an intronic presenilin-1 mutation (in intron 4). Mean age at onset of symptoms was 37.4 years [95% confidence interval (CI): 36.6-38.2 years], mean age at death was 44.7 years (95% CI: 43.1-46.3 years) and mean duration of illness was 7.3 years (95% CI: 5.9-8.7 years). Myoclonus and seizures were prominent features of this pedigree. In the four cases for whom neuropsychometric data were available, verbal memory impairment preceded visual memory deficits; naming was relatively preserved until late in the disease. One of these four cases underwent serial volumetric MRI scans demonstrating in vivo brain tissue loss of 3.9% (38.9 ml, annualized rate of atrophy: 1. 7%) over 22 months of follow-up. The four individuals who had necropsies demonstrated the neuropathological hallmarks of Alzheimer's disease. Apolipoprotein E (APOE) status was assessed in five individuals: the case with the youngest age at onset at 33 years of age was found to be homozygous epsilon4/epsilon4, > 1 SD below the mean age of onset for those of known APOE genotype (36.4 +/- 2.3 years, mean +/- SD), and > 2 SDs below the mean age of onset for the pedigree as a whole (37.4 +/- 1.7 years, mean +/- SD). APOE genotype may therefore modulate age at onset in this pedigree.

Adult↗
PubMed2000

A volumetric study of hippocampus and amygdala in depressed patients with subjective memory problems.

MRI was used to measure amygdalar and hippocampal volumes in 14 nondemented depressed patients who persistently complained of "memory" difficulties and in 14 control subjects. Mild neuropsychological impairment had been detected in 5 patients before the study but had later improved. The volume of the left amygdala was smaller in depressed subjects, and there was a trend for smaller left hippocampus in the 5 patients who had exhibited mild cognitive impairment. The authors conclude that subjective memory complaints in depressed patients do not translate into a clinical picture of dementia, but that abnormalities in the amygdala and hippocampus may be relevant in explaining affective and cognitive symptoms.

Adult↗
PubMed1999

Correlation between rates of brain atrophy and cognitive decline in AD.

Twenty-nine untreated patients diagnosed with probable AD and 15 control patients underwent two or more clinical and volumetric MRI assessments with intervals ranging from 5 months to 6 years. The change in global cerebral volume for an individual was calculated by a novel method of registration and subtraction of serial scans. Rate of global cerebral volume loss correlated strongly with rate of change in Mini-Mental State Examination scores (r = 0.80, p < 0.001), implying clinical relevance to this marker of progression.

Aged↗
PubMed1999

Pathogenic presenilin 1 mutations (P436S & I143F) in early-onset Alzheimer's disease in the UK. Mutations in brief no. 223. Online.

Familial Alzheimer's disease (AD) is an autosomal dominant disorder characterized by memory impairment and multiple cognitive deficits which occurs in mid to late life. Early onset AD has been associated with mutations in three genes, of which presenilin 1 (PS1) mutations are the most frequent. We sequenced the open reading frame from genomic DNA of a series of 21 early onset AD (AD3) UK families in which there were at least two affected individuals in two or more generations with a diagnosis of probable or definite AD. We found PS1 mutations in six of these families with no sequence variation in the remaining 15. The six families contained between them five different mutations of which two, I143F and P436S, have not been found elsewhere. I143F shows incomplete penetration within the affected family. P436S is the most carboxy-terminal presenilin 1 mutation reported to date.

Alzheimer Disease↗
PubMed1999

Diagnosis of early Alzheimer's disease.

Current criteria for the diagnosis of Alzheimer's disease require that the patient also fulfils the criteria for dementia. This means inevitably that the disease is well-established. As treatments become available there is an important need for early diagnosis. There are two components to diagnosis; the recognition that cognitive performance is below that which would be anticipated for the individual and secondly to relate this to a specific disease process. Research studies need to identify the very earliest changes i.e. before symptoms commence. Such studies have focused on at risk populations either by virtue of age or a positive family history. Both groups have demonstrated that memory is the salient early feature, particularly verbal memory, impairment of which may precede overt symptoms by many years. The other major approach has been that of neuroimaging. Group studies of at risk individuals, for example for those who carry an apoE4 allele, have shown relative biparietal, bitemporal hypometabolism in the at risk group. Similarly, structural neuroimaging may show hippocampal atrophy at an early stage. Serial studies to determine rate of change, may be more valuable than single cross-sectional studies. Recent techniques of positional matching and registration allow precise quantitation of rates of cerebral atrophy which may be useful in early diagnosis.

Alzheimer Disease↗
PubMed1998

CANDID--Counselling and Diagnosis in Dementia: a national telemedicine service supporting the care of younger patients with dementia.

OBJECTIVES: To audit and evaluate the introduction of a novel support service for younger people with dementia, their families and the professionals caring for them. DESIGN: A retrospective review of all calls received by a telephone helpline over a 2-year period. SETTING: CANDID (Counselling and Diagnosis in Dementia) offers direct access, by telephone and e-mail, to specially trained nurse/counsellors who record the caller's query, provide emotional support and practical advice. In addition to general advice, clinical details are held for patients registered with the service so that the advice given can be tailored to the patient's specific need and routed via the general practitioner for action. Advice is reviewed by a consultant neurologist and psychiatrist. SUBJECT: Callers to the CANDID helpline, who made a total of 1,121 calls. MAIN OUTCOME MEASURES: Details of the caller and of the patient they were caring for. Reason for calling and advice given to the caller RESULTS: Of the 1,121 calls received during the first 2 years of operation, 547 were 'registered' calls relating to 241 individual patients where more specific advice could be given through the GP. The remaining 574 'generic' calls were from members of the public and healthcare professionals who had heard about the service and were seeking information and advice. Reasons for calls were divided into three broad categories: general information; clinical advice; and advice on social issues. Among the registered callers, 50% of calls were for clinical advice. Letters were sent to GPs on 67 occasions; 48 (56%) provided information only for the GP, 16 (24%) advised a secondary referral and eight (12%) advised on the use of specific medication. CONCLUSION: The service has become rapidly accepted and used by families of patients and members of the public. Healthcare professionals have made less use of the service than anticipated, but it is hoped that this will increased as information about the service becomes disseminated.

Adolescent↗