The influence of childhood intelligence, social class, education and social mobility on memory and memory decline in late life.

In an observational longitudinal study of a sub-sample of the Aberdeen 1936 birth cohort, from age 62 to 77 years, we investigated childhood intelligence, social class, education, life-course social mobility, memory test performance and memory decline in late life. We examined 388 local residents who had attended school in Aberdeen in 1947 and measured Auditory-Verbal Learning Test (AVLT) at recruitment age about 64 years and up to five times until age about 77 years. Better performance at age about 64 on AVLT was predicted by early socioeconomic status (SES), social mobility and childhood intelligence. The trajectory of AVLT decline was steeper in those who had received less education. This relationship was independent of childhood ability, sex, SES in childhood and social mobility. The protection of memory by education suggests that education supports resilience to age-related cognitive impairment. Upward social mobility does not enhance this effect, suggesting that resilience to age-related decline may be established in early life.

Life course socioeconomic status and the decline in information processing speed in late life.

Low socio-economic status is a recognised composite measure made up of income, education and occupational social class, which is a risk factor for poor physical and mental health and late life dementia. Here, we distinguish between components of childhood socioeconomic status to explore their separate influences of childhood and adult occupational social class (OSC), childhood mental ability and education on late life cognitive ability and change trajectories. Cognitive data were collected longitudinally from a sub-sample (N = 478) of the Aberdeen 1936 birth cohort tested on up to 5 occasions between ages 63 and 78 years. Age 11 mental ability scores were available for all participants. We used longitudinal multi-level linear modelling to explore models of cognitive change that distinguished between the possible influences of parental occupation, participants' own occupation as adults, duration of formal education, childhood mental ability and the participants' own occupation. We showed that parental occupation and the participants' own occupation are independently associated with cognition in late life, but do not influence the trajectory of cognitive change. However, when models include childhood mental ability and education the influence of parental and participant occupation is no longer significant. The association in these data between parental occupation and late life cognitive variation is accounted for by childhood mental ability and duration of formal education. However, we cannot exclude the possibility that parental occupation in early life influences early life mental ability and duration of education. The trajectory of change with age is similar across all models, with none of the life course factors (education, parental and participant occupational social class and childhood ability) significantly co-varying with the trajectory of cognitive variation.

Planar and SPECT ventilation/perfusion imaging and computed tomography for the diagnosis of pulmonary embolism: A systematic review and meta-analysis of the literature, and cost and dose comparison.

Diagnosing acute pulmonary embolism (PE) is an indication for scintillation V/Q imaging (planar and SPECT) and/or CTPA. This study reviews, compares and aggregates the published diagnostic performance of each modality and assesses the short-term consequences in terms of diagnostic outcomes, monetary cost, and radiation burden. We performed a formal literature review of available data and aggregated the finding using a summary receiver operating characteristic. A decision tree approach was used to estimate cost and dose per correct diagnosis. The review found 19 studies, which comprised 27 data sets (6393 examinations, from 5923 patients). The results showed that planar V/Q was significantly inferior to both V/Q SPECT and CTPA with no difference between the latter two. CTPA represents best value; £129 per correct diagnosis compared to £243 (SPECT) and £226 (planar). In terms of radiation burden V/Q SPECT was the most effective with a dose of 2.12 mSv per correct diagnosis compared with 3.46 mSv (planar) and 4.96 (CTPA) mSv. These findings show no performance difference between V/Q SPECT and CTPA; planar V/Q is inferior. CTPA is clearly the most cost effective technique. V/Q SPECT should be considered in situations where radiation dose is of concern or CTPA is inappropriate.

Automatic classification of DMSA scans using an artificial neural network.

DMSA imaging is carried out in nuclear medicine to assess the level of functional renal tissue in patients. This study investigated the use of an artificial neural network to perform diagnostic classification of these scans. Using the radiological report as the gold standard, the network was trained to classify DMSA scans as positive or negative for defects using a representative sample of 257 previously reported images. The trained network was then independently tested using a further 193 scans and achieved a binary classification accuracy of 95.9%. The performance of the network was compared with three qualified expert observers who were asked to grade each scan in the 193 image testing set on a six point defect scale, from 'definitely normal' to 'definitely abnormal'. A receiver operating characteristic analysis comparison between a consensus operator, generated from the scores of the three expert observers, and the network revealed a statistically significant increase (α < 0.05) in performance between the network and operators. A further result from this work was that when suitably optimized, a negative predictive value of 100% for renal defects was achieved by the network, while still managing to identify 93% of the negative cases in the dataset. These results are encouraging for application of such a network as a screening tool or quality assurance assistant in clinical practice.

The biological correlates of macroscopic breast tumour structure measured using fractal analysis in patients undergoing neoadjuvant chemotherapy.

Breast cancers are evolving, multi-scale systems that are characterized by varied complex spatial structures. In this study, we measured the structural characteristics of 33 breast tumours in patients who were to receive neoadjuvant chemotherapy using dynamic contrast enhanced MRI and fractal geometry. The results showed a significant association between fractal measurements and tumour characteristics. The fractal dimension was associated with receptor status (ER and PR) and the fractal fit was associated with response to chemotherapy, measured using a validated pathological response scale, tumour grade and size. This study describes structure measures that may be a consequence of known prognostic factors during the initial and/or maturation phase of tumour growth. These results suggest that measuring tumour structure in this way can predict an individual's response to neoadjuvant therapy and may identify those who will benefit least from neoadjuvant chemotherapy, allowing alternative treatment options to be selected in those patients.

The use of FDG-PET in assessing axillary lymph node status in breast cancer: a systematic review and meta-analysis of the literature.

Axillary lymph node status is the most powerful prognostic indicator in patients with breast cancer. FDG-PET has been suggested as a non-invasive method of staging the axilla. The aim of this study was to review and aggregate all studies that measured the performance of FDG-PET in patients with breast cancer, using surgically obtained axillary histology as a reference, in a meta-analysis. A systematic review of the literature was performed and data extracted from all eligible studies. These were then analysed using meta-analysis software and summary receiver operating characteristic (SROC) curves were plotted for the aggregate data. The data was then tested to determine which parameters impacted on the sensitivity and specificity of the studies. Sensitivities ranging from 20 to 100% and specificities ranging from 65 to 100% have been reported. An aggregated ROC analysis found an area under the curve of 0.95 (95% CI 0.91-0.97) and a Q* value of 0.89 (95% CI 0.85-0.92) in a total of 25 studies involving 2,460 patients. The AUC and Q* values indicated little difference between the compared study characteristics. The performance of the technique currently remains below, which is required to replace assessment of axillary node status by surgical biopsy and histological assessment. However, sensitivity and specificity are high and FDG-PET may have a role to play under particular circumstances. Moreover, the additional benefit of an assessment of distal metastatic spread provided by FDG-PET requires further investigation.

Baseline MRI delivery characteristics predict change in invasive ductal breast carcinoma PET metabolism as a result of primary chemotherapy administration.

BACKGROUND: The aim of the study was to investigate whether pre-therapy vascular delivery assessment [using dynamic contrast enhanced magnetic resonance imaging (DCE-MRI)] can predict reduction in breast cancer metabolism [detected using 2-[(18)F] fluoro-2-deoxy-D-glucose positron emission tomography ((18)F(-)FDG-PET)] after a single cycle of chemotherapy. Reduction in (18)F-FDG PET metabolism has previously been shown to correlate with histological response to primary chemotherapy. PATIENTS AND METHODS: Seventeen patients with large or locally advanced invasive ductal carcinomas of the breast were imaged using DCE-MRI and (18)F-FDG-PET prior to therapy and 20 days after the first cycle of chemotherapy. MRI data were analysed using a multi-compartment model. PET data were analysed using standardised uptake value (SUV) analysis. RESULTS: A significant association (P <0.05) was observed between pre-therapy DCE-MRI vascular parameters and the reduction in PET metabolism resulting from administration of one cycle of chemotherapy. CONCLUSIONS: A relationship was demonstrated between pre-therapy DCE-MRI vascular parameters and the reduction in PET metabolism after a single cycle of chemotherapy. This suggests that reduction in PET metabolism as a result of chemotherapy may be dependent, at least in part, on pre-therapy vascular delivery. These pre-therapy vascular characteristics may be suitable for use as a surrogate measure for initial chemotherapy delivery, a key factor in chemotherapeutic efficacy.

The use of the Levenberg-Marquardt curve-fitting algorithm in pharmacokinetic modelling of DCE-MRI data.

The use of curve-fitting and compartmental modelling for calculating physiological parameters from measured data has increased in popularity in recent years. Finding the 'best fit' of a model to data involves the minimization of a merit function. An example of a merit function is the sum of the squares of the differences between the data points and the model estimated points. This is facilitated by curve-fitting algorithms. Two curve-fitting methods, Levenberg-Marquardt and MINPACK-1, are investigated with respect to the search start points that they require and the accuracy of the returned fits. We have simulated one million dynamic contrast enhanced MRI curves using a range of parameters and investigated the use of single and multiple search starting points. We found that both algorithms, when used with a single starting point, return unreliable fits. When multiple start points are used, we found that both algorithms returned reliable parameters. However the MINPACK-1 method generally outperformed the Levenberg-Marquardt method. We conclude that the use of a single starting point when fitting compartmental modelling data such as this produces unsafe results and we recommend the use of multiple start points in order to find the global minima.

The effects of renal variation upon measurements of perfusion and leakage volume in breast tumours.

Dynamic contrast enhanced MRI (DCE-MRI) and pharmacokinetic models have been used to measure tumour permeability (K(trans)) and leakage volume (ve) in numerous studies. The construction of pharmacokinetic models describing such tissue properties relies on defining the blood plasma concentration of contrast agent with respect to time (Cp(t)). When direct measurement is not possible a bi-exponential decay has been applied using data from healthy volunteers. This work investigates, by simulation, the magnitude of errors resulting from this definition with respect to normal variation in renal function and for cases with renal impairment. Errors up to 23% in ve and 28% in K(trans) were found for the normal simulations, and 67% in ve and 61% in K(trans) for the impaired simulations. If this bi-exponential curve is used as an input function to the generalized kinetic model and used in oncology, estimates of tissue permeability and leakage volume will possess large errors due to variation in Cp(t) curves between subjects.

Plasma vitamin C, cholesterol and homocysteine are associated with grey matter volume determined by MRI in non-demented old people.

We studied 82 non-demented old people and, using MRI, derived measures of grey and white matter and intracranial volumes. Controlling for sex and intracranial volume, we related grey and white matter volumes to plasma concentrations of vitamins C, B(12), folate, homocysteine, cholesterol, triglycerides, high density and low density (LDL) lipoproteins, and to red blood cell folate and glycated haemoglobin concentrations (HbA1(c)). We found that lower grey matter volume was associated with lower plasma vitamin C and higher homocysteine, cholesterol and LDL. Lower blood cell folate was also associated with lower grey matter volume but HbA1(c) was not. These data are consistent with the putative benefits of dietary vitamin C and folate intake and the role of cholesterol in age related neurodegeneration.

Brain white matter lesions detected by magnetic resonance [correction of resosnance] imaging are associated with balance and gait speed.

OBJECTIVE: To investigate the relations between premorbid and current mental ability, mood, and white matter signal abnormalities detected by T2 weighted brain magnetic resonance imaging (MRI) and impairment of balance and mobility in older adults. METHODS: 97 subjects from the Aberdeen 1921 birth cohort underwent brain MRI, evaluation of balance, and measurement of gait speed. White matter hyperintensities detected on T2 weighted MRI scans were rated by three independent raters on three variables: white matter lesions; periventricular lesions; and brain stem lesions. RESULTS: Decreased gait speed was correlated with impaired visual acuity (p = 0.020), shorter stature (p = 0.008), a lower childhood IQ (p = 0.030), a lower current Raven's progressive matrices score (Raven score) (p < 0.001), a higher hospital anxiety and depression scale (HADS) score (p = 0.004), and an increased grade of brain stem lesions on MRI. Inability to balance was correlated with Raven score (p = 0.042), brain stem lesions (p = 0.003), white matter lesions (p = 0.003), and periventricular lesions (p = 0.038). Binary logistic regression identified brain stem lesions (odds ratio (OR) 0.22; 95% confidence interval 0.09 to 0.54) and HADS depression score (OR 0.75; 0.58 to 0.97) as the only significant associations with balance. Structural equation modelling detected an association between two latent traits representing white matter disease and an integrating function, respectively. CONCLUSIONS: In this cohort, white matter lesions, periventricular lesions, and brain stem lesions were associated with impaired balance. Current mental ability was strongly related to gait speed. There appears to be a concordance between motor skills and intellect in old age, which is degraded by white matter disease.

Automatic detection of coronary artery disease in myocardial perfusion SPECT using image registration and voxel to voxel statistical comparisons.

The purpose of this study was to compare the performance of automatic detection of coronary artery disease (CAD) with that of expert observers. A male and female normal image template was constructed from normal stress technetium-99m single photon emission computed tomography (SPECT) studies. Mean and standard deviation images for each sex were created by registering normal studies to a standard shape and position. The test group consisted of 104 patients who had been routinely referred for SPECT and angiography. The gold standard for CAD was defined by angiography. The test group studies were registered to the respective templates and the Z-score was calculated for each voxel. Voxels with a Z-score greater than 5 indicated the presence of CAD. The performance of this method and that of three observers were compared by continuous receiver operating characteristic (CROC) analysis. The overall sensitivity and specificity for automatic detection were 73% and 92%, respectively. The area (Az) under the CROC curve (+/-1 SE) for automatic detection of CAD was 0.88+/-0.06. There was no statistically significant difference between the performances of the three observers in terms of Az and that of automatic detection (P> or =0.25, univariate Z-score test). The use of this automated statistical mapping approach shows a performance comparable with experienced observers, but avoids inter-observer and intra-observer variability.

Dynamic contrast enhanced MRI of the axilla in women with breast cancer: comparison with pathology of excised nodes.

Axillary lymph node status is the most important prognostic factor in breast cancer patients and is currently determined by surgical dissection. This study was performed to assess whether dynamic gadopentetate dimeglumine (Gd) enhanced MRI is an accurate method for non-invasive staging of the axilla. 47 women with a new primary breast cancer underwent pre-operative dynamic Gd enhanced MRI of the ipsilateral axilla. Lymph node enhancement was quantitatively analysed using a region of interest method. Enhancement indices and nodal area were compared with histopathology of excised nodes using a receiver operating characteristic (ROC) curve approach. 10 patients had axillary metastases pathologically and all had > or =1 lymph node with an enhancement index of >21% and a nodal area of >0.4 cm(2). 37 patients had negative axillary nodes pathologically. 20 of these had enhancement indices <21% and nodal areas <0.4 cm(2). Using this method, a sensitivity of 100%, a specificity of 56%, a positive predictive value of 38% and a negative predictive value of 100% could be achieved. Using this method of quantitative assessment, dynamic Gd enhanced MRI may be a reliable method of predicting absence of axillary nodal metastases in women with breast cancer, thereby avoiding axillary surgery in women with a negative MRI study.

Neuropsychologic correlates of brain white matter lesions depicted on MR images: 1921 Aberdeen Birth Cohort.

PURPOSE: To examine relationships between brain white matter hyperintensities depicted at magnetic resonance (MR) imaging and performance on neuropsychologic tests in community-dwelling elderly adults. MATERIALS AND METHODS: The 1921 Aberdeen Birth Cohort is a subsample of survivors of the Scottish Mental Survey of 1932 whose mental ability was tested at 11 years of age. Ninety-five of these subjects agreed to undergo brain MR imaging, an examination of general health, and a neuropsychologic evaluation. White matter hyperintensities detected at T2-weighted MR imaging were rated by using a semiquantitative method yielding two continuous variables: white matter lesions and periventricular lesions. Cognitive ability, including crystallized and fluid intelligence domains, was assessed with standard neuropsychologic tests. RESULTS: Rating scores of white matter lesions were normally distributed (on a devised scale) with means of 1.14 for white matter lesions and 1.28 for periventricular lesions. Intra- and interobserver reliability coefficients for scores were high, generally above 0.7. There were significant correlations of medium effect size between the T2-weighted MR imaging-depicted white matter lesions and performance on tests of fluid-type intelligence. No significant correlation was demonstrated between white matter lesion ratings and tests of crystallized intelligence. CONCLUSION: Lower fluid-type ("prevailing") intelligence test scores were associated with increased severity of white matter lesion ratings but not crystallized-type ("premorbid") intelligence test scores. This indicates that MR imaging-depicted white matter lesions are of clinical importance.

The use of SPAMM to assess spatial distortion due to static field inhomogeneity in dental MRI.

In planning placement of dental implants using MRI, a SPAMM (spatial modulation of magnetization) magnetization preparation sequence was incorporated into a spin-echo imaging sequence. A phantom was imaged with a ferromagnetic object attached. Spatial distortion due to deviations in Larmor frequency was detected by a deviation of SPAMM lines. Both SPAMM line deviation and interline spacing were found to agree with a deltaB0 map generated from phase images. Imaging of a volunteer with and without typically used metallic implants positioned in a template showed SPAMM line deviations to correlate with expected deviations in vivo. SPAMM lines showed possible distortion due to chemical shift in the bone marrow and the presence of titanium implants to be insignificant. SPAMM may thus be used to provide a qualitative estimate of the accuracy of the MRI image when planning dental implants.

An assessment of perfusion deficits in decompression illness using 99Tcm HMPAO SPET and statistical parametric mapping.

AIM: The aim of this study was to use statistical parametric mapping (SPM) to investigate differences in the regional cerebral blood flow (rCBF) of decompression illness (DCI) and non-diving control subjects. METHODS: Twenty DCI subjects were imaged using 99Tcm hexamethylproplylene amine oxime (HMPAO) single photon emission tomography (SPET) within days of their incident of DCI, and on a second occasion between 2 and 27 months after their DCI event. SPM was used to make a comparison between decompression illness studies and a second group of non-diving control studies for both early and late imaging of DCI. A paired comparison of early and late imaging was also performed testing for correlation between time of imaging and changes in the rCBF pattern. RESULTS: The comparison between control subjects and early imaging of decompression illness showed a large, significant (P = 0.002), irregularly shaped, multi-focal area of reduced uptake in the left occipito-parieto-temporal region of the brain. Comparisons between control and repeat decompression illness imaging studies showed two areas of reduced uptake. The first was similar to that found in the initial comparison although it was less significant (P = 0.035). The second region was similar but contra-lateral to the first region with significance P < 0.001. An attempt to correlate any changes in rCBF with the time that elapsed between each set of imaging found no areas of significant correlation. CONCLUSION: 99Tcm HMPAO SPET images of decompression illness display areas of reduced perfusion, which persist in the majority of cases.

Comparison of methods for quantification of transient ischaemic dilation in myocardial perfusion SPET.

The purpose of this study was to compare six methods of measuring the left ventricular (LV) transient ischaemic dilation (TID) ratio during stress-rest myocardial perfusion single-photon emission tomography (SPET). The TID ratio was defined as the mean LV short-axis area at stress divided by the mean LV area of similar slices at rest. The centre of the LV wall was defined as either the maximum, mean or median of the radial short-axis count profiles. The area within the endocardial wall was also calculated for each definition of the LV wall centre. We identified 50 consecutive patients undergoing dipyridamole technetium-99m-tetrofosmin SPET imaging and angiography. Continuous receiver operating characteristic (CROC) analysis showed no significant difference between the six methods in terms of identifying severe coronary artery disease (P >0.47). Algorithms using the mean or the median value in the profile were significantly more robust than those using the maximum (P <0.0005). TID measured by all the algorithms is an indicator of severe coronary disease (P < 0.05). The algorithms compared provide a repeatable, quantitative and specific measure of the TID ratio.

HMPAO SPECT imaging of Alzheimer's disease patients with similar content-specific autobiographic delusion: comparison using statistical parametric mapping.

UNLABELLED: Delusional behavior and thinking are common symptoms in Alzheimer's disease (AD). In the past, these delusions have been considered to be psychotic complications of global neurologic dysfunction. Recently, authors have suggested that content-specific delusions in AD are associated with discrete regional abnormalities of the right hemisphere. METHOD: This study compared 99mTc-hexamethyl propyleneamine oxime (HMPAO) SPECT images of a group of AD patients with a similar autobiographic delusion with a group of AD patients without delusions and a group of AD patients with a range of delusions but without autobiographic content. The reconstructed SPECT data were compared using a statistical parametric mapping technique. RESULTS: The autobiographic AD group had a significant area of hypoperfusion in the right frontal lobe when compared with the 2 other groups. The area of hypoperfusion included parts of Brodmann's areas 9 and 10. Region 9 has been identified previously as having a role in episodic memory retrieval. CONCLUSION: This result suggests that autobiographic delusions in AD may have an identifiable neuropsychologic mechanism and that it may be possible to identify an organic cause in some patients using 99mTc-HMPAO SPECT.

Assessment of maxillary sinus volume for the sinus lift operation by three-dimensional magnetic resonance imaging.

OBJECTIVES: To calculate sinus and bone graft volumes and vertical bone heights from sequential magnetic resonance imaging (MRI) examinations in patients undergoing a sinus lift operation. METHODS: MRI scans were obtained pre-operatively and at 10 days and 10 weeks post-operatively, using a 0.95 tesla MRI scanner and a three-dimensional (3D) magnetisation prepared, rapid acquisition gradient-echo (MP-RAGE) sequence. RESULTS: Estimates of the bone graft volumes required for a desired vertical bone height were made from the pre-operative MRI scan. Measurements of the graft volumes and bone heights actually achieved were made from the post-operative scans. The MRI appearance of the graft changed between the 10 day and 10 week scans. CONCLUSIONS: We have proposed a technique which has the potential to give the surgeon an estimate of the optimum volume of graft for the sinus lift operation from the pre-operative MRI scan alone and demonstrated its application in a single patient. Changes in the sequential MRI appearance of the graft are consistent with replacement of fluid by a matrix of trabecular bone.

Changes in the rCBF images of patients with Alzheimer's disease receiving Donepezil therapy.

Alzheimer's disease is associated with a loss in presynaptic cholinergic function. It has been suggested that cholinergic inhibitors such as donepezil hydrochloride (Donepezil) could restore this function and improve some of the symptoms of Alzheimer's disease. Previous work has shown that Donepezil improves cognitive and global function in patients with mild to moderate Alzheimer's disease. This study reviewed retrospectively 12 patients who had previously had a 99Tcm-hexamethylpropylene amine oxime (99Tcm-HMPAO) single photon emission tomography (SPET) regional cerebral blood flow (rCBF) examination and had gone on to receive Donepezil therapy. These patients were recalled for a further 99Tcm-HMPAO SPET rCBF examination and the image data sets were compared. The results showed an overall increase in global cerebral blood flow (P = 0.04) averaged over the group with a percentage change in blood flow ranging from -1.8% to 6.4%. However, some patients showed a slight decrease in blood flow. When the data were analysed in terms of regional cerebral blood flow, we found that the most significant increase in blood flow occurred in the frontal lobes (P = 0.02).