[show abstract][hide abstract] ABSTRACT: OBJECTIVE: MRI at 3 T is said to be more accurate than 1.5 T MR, but costs and other practical differences mean that it is unclear which to use. METHODS: We systematically reviewed studies comparing diagnostic accuracy at 3 T with 1.5 T. We searched MEDLINE, EMBASE and other sources from 1 January 2000 to 22 October 2010 for studies comparing diagnostic accuracy at 1.5 and 3 T in human neuroimaging. We extracted data on methodology, quality criteria, technical factors, subjects, signal-to-noise, diagnostic accuracy and errors according to QUADAS and STARD criteria. RESULTS: Amongst 150 studies (4,500 subjects), most were tiny, compared old 1.5 T with new 3 T technology, and only 22 (15 %) described diagnostic accuracy. The 3 T images were often described as "crisper", but we found little evidence of improved diagnosis. Improvements were limited to research applications [functional MRI (fMRI), spectroscopy, automated lesion detection]. Theoretical doubling of the signal-to-noise ratio was not confirmed, mostly being 25 %. Artefacts were worse and acquisitions took slightly longer at 3 T. CONCLUSION: Objective evidence to guide MRI purchasing decisions and routine diagnostic use is lacking. Rigorous evaluation accuracy and practicalities of diagnostic imaging technologies should be the routine, as for pharmacological interventions, to improve effectiveness of healthcare. KEY POINTS : • Higher field strength MRI may improve image quality and diagnostic accuracy. • There are few direct comparisons of 1.5 and 3 T MRI. • Theoretical doubling of the signal-to-noise ratio in practice was only 25 %. • Objective evidence of improved routine clinical diagnosis is lacking. • Other aspects of technology improved images more than field strength.
European Radiology 06/2012; 22(11):2295-2303. · 3.55 Impact Factor
[show abstract][hide abstract] ABSTRACT: To investigate in older adults without dementia the relationships between socioeconomic status (SES) in childhood and magnetic resonance imaging (MRI)-derived brain volume measures typical of brain aging and Alzheimer's disease (AD).
Using a cross-sectional and longitudinal observation approach, we invited volunteers without dementia, all born in 1936, and who were participants in the 1947 Scottish Mental Survey, for MR brain imaging; 249 of 320 (77%) agreed. We measured whole brain and hippocampal volumes and recorded childhood SES history, the number of years of education undertaken, and adult SES history. Mental ability at age 11 years was recorded in 1947 and was also available.
Analysis shows a significant association between childhood SES and hippocampal volume after adjusting for mental ability at age 11 years, adult SES, gender, and education.
A significant association between childhood SES and hippocampal volumes in late life is consistent with the established neurodevelopmental findings that early life conditions have an effect on structural brain development. This remains detectable more than 50 years later.
Annals of Neurology 05/2012; 71(5):653-60. · 11.19 Impact Factor
[show abstract][hide abstract] ABSTRACT: Fractal measures such as fractal dimension (FD) can quantify the structural complexity of the brain. These have been used in clinical neuroscience to investigate brain development, ageing and in studies of psychiatric and neurological disorders. Here, we examined associations between the FD of white matter and cognitive changes across the life course in the absence of detectable brain disease. The FD was calculated from segmented cerebral white matter MR images in 217 subjects aged about 68years, in whom archived intelligence scores from age 11years were available. Cognitive test scores of fluid and crystallised intelligence were obtained at the time of MR imaging. Significant differences were found (intracranial volume, brain volume, white matter volume and Raven's Progressive Matrices score) between men and women at age 68years and novel associations were found between FD and measures of cognitive change over the life course from age 11 to 68years. Those with greater FD were found to have greater than expected fluid abilities at age 68years than predicted by their childhood intelligence and less cognitive decline from age 11 to 68years. These results are consistent with other reports that FD measures of cortical structural complexity increase across the early life course during maturation of the cerebral cortex and add new data to support an association between FD and cognitive ageing.
[show abstract][hide abstract] ABSTRACT: 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.
Breast Cancer Research and Treatment 03/2012; 133(3):1199-206. · 4.47 Impact Factor
[show abstract][hide abstract] ABSTRACT: To document accessible magnetic resonance (MR) brain images, metadata and statistical results from normal older subjects that may be used to improve diagnoses of dementia.
We systematically reviewed published brain image databanks (print literature and Internet) concerned with normal ageing brain structure.
From nine eligible databanks, there appeared to be 944 normal subjects aged ≥60 years. However, many subjects were in more than one databank and not all were fully representative of normal ageing clinical characteristics. Therefore, there were approximately 343 subjects aged ≥60 years with metadata representative of normal ageing, but only 98 subjects were openly accessible. No databank had the range of MR image sequences, e.g. T2*, fluid-attenuated inversion recovery (FLAIR), required to effectively characterise the features of brain ageing. No databank supported random subject retrieval; therefore, manual selection bias and errors may occur in studies that use these subjects as controls. Finally, no databank stored results from statistical analyses of its brain image and metadata that may be validated with analyses of further data.
Brain image databanks require open access, more subjects, metadata, MR image sequences, searchability and statistical results to improve understanding of normal ageing brain structure and diagnoses of dementia. KEY POINTS : • We reviewed databanks with structural MR brain images of normal older people. • Among these nine databanks, 98 normal subjects ≥60 years were openly accessible. • None had all the required sequences, random subject retrieval or statistical results. • More access, subjects, sequences, metadata, searchability and results are needed. • These may improve understanding of normal brain ageing and diagnoses of dementia.
European Radiology 02/2012; 22(7):1385-94. · 3.55 Impact Factor
[show abstract][hide abstract] ABSTRACT: The cognitive reserve hypothesis explains the disparity between clinical and pathological phenotypes and why, in two individuals with the same extent of neuropathology, one may be demented while the other remains cognitively intact. We examined the balance between brain magnetic resonance imaging measures of the two most common pathologies associated with brain ageing, cerebrovascular disease and Alzheimer's disease, and parameters of cerebral reserve in well-characterized participants born in 1936, for whom childhood intelligence is known. Brain magnetic resonance imaging was carried out at 1.5T using fluid attenuation inversion recovery and T(1)-weighted volumetric sequences in 249 participants. Cerebrovascular disease was quantified by measuring brain white matter hyperintensities on fluid attenuation inversion recovery images using Scheltens' scale and Alzheimer's disease was measured from volumetric data using FreeSurfer to extract whole brain volume and hippocampal volumes in turn. The effect of these measures of brain burden on life-long cognitive ageing from the age of 11 to 68 years was compared with the effect of educational attainment and occupational grade using structural equation modelling. Complete brain burden and reserve data were available in 224 participants. We found that educational attainment, but not occupation, has a measurable and positive effect, with a standardized regression weight of +0.23, on late life cognitive ability in people without cognitive impairment aged 68 years, allowing for the influence of childhood intelligence and the two most common subclinical brain pathological burdens in the ageing brain. In addition, we demonstrate that the magnitude of the contribution of education is greater than the negative impact of either neuropathological burden alone, with standardized regression weights of -0.14 for white matter hyperintensities and -0.20 for hippocampal atrophy. This study illustrates how education counteracts the deleterious effects of cerebrovascular disease and Alzheimer's disease and highlights the importance of quantifying cognitive reserve in dementia research.
[show abstract][hide abstract] ABSTRACT: Aberrant motor behaviour (AMB) in Alzheimer's disease shares behavioural correlates with obsessive compulsive disorder (OCD). We investigated whether AMB was also comparable in terms of metabolic activity in the orbitofrontal cortex (OFC), an area shown to be hyperactive in OCD. In this study 135 patients meeting research criteria for Alzheimer's disease were identified from a database of patients recruited as part of a phase II drug trial. These patients were assessed using the Neuropsychiatric Inventory, the Alzheimer's disease assessment scale, cognitive subscale and perfusion SPECT performed with 99Tc(m) hexamethylpropyleneamine oxime. Regions of interest were created for orbitofrontal cortices and basal ganglia. In 35 patients with AMB, adjusted tracer uptake was greater in the OFC. This reached statistical significance in right superior, left superior, right medial and left medial orbital gyri (p < 0.05). The association between AMB and hyperactivity in the OFC remained significant after adjusting for the presence of anxiety. These results parallel the OFC hypermetabolism consistently seen in OCD. One model of OCD, proposes that dysfunctional interactions between frontal regions, including the OFC, produce the characteristic symptoms of OCD. The behaviour is though to be brought about by a perceived incompleteness of performing a task and is caused by an error in normal reward signals initiated upon task completion. These finding indicate that AMB in Alzheimer's disease are brought about by the same mechanistic failure.
Behavioural brain research 09/2011; 222(2):375-9. · 3.22 Impact Factor
[show abstract][hide abstract] ABSTRACT: We investigated the association between individual differences in cognitive performance in old age and the approximate entropy (ApEn) measured from functional magnetic resonance imaging (fMRI) data acquired from 40 participants of the Aberdeen Birth Cohort 1936 (ABC1936), while undergoing a visual information processing task: inspection time (IT). Participants took a version of the Moray House Test (MHT) No. 12 at age 11, a valid measure of childhood intelligence. The same individuals completed a test of non-verbal reasoning (Raven's Standard Progressive Matrices [RPM]) aged about 68 years. The IT, MHT and RPM scores were used as indicators of cognitive performance. Our results show that higher regional signal entropy is associated with better cognitive performance. This finding was independent of ability in childhood but not independent of current cognitive ability. ApEn is used for the first time to identify a potential source of individual differences in cognitive ability using fMRI data.
[show abstract][hide abstract] ABSTRACT: The variation of the native T(1) (T(10)) of different tissues and B(1) transmission-field inhomogeneity at 3 T are major contributors of errors in the quantification of breast dynamic contrast-enhanced MRI. To address these issues, we have introduced new enhancement indices derived from saturation-recovery snapshot-FLASH (SRSF) images. The stability of the new indices, i.e., the SRSF enhancement factor (EF(SRSF)) and its simplified version (EF'(SRSF)) with respect to differences in T(10) and B(1) inhomogeneity was compared against a typical index used in breast dynamic contrast-enhanced MRI, i.e., the enhancement ratio (ER), by using computer simulations. Imaging experiments with Gd-DTPA-doped gel phantoms and a female volunteer were also performed. A lower error was observed in the new indices compared to enhancement ratio in the presence of typical T(10) variation and B(1) inhomogeneity. At changes of relaxation rate (ΔR(1)) of 8 s(-1), the differences between a T(10) of 1266 and 566 ms are <1, 12, and 58%, respectively, for EF(SRSF), EF'(SRSF), and ER, whereas differences of 20, 8, and 51%, respectively, result from a 50% B(1) field reduction at the same ΔR(1). These quantification techniques may be a solution to minimize the effect of T(10) variation and B(1) inhomogeneity on dynamic contrast-enhanced MRI of the breast at 3 T.
Magnetic Resonance in Medicine 06/2011; 67(2):531-40. · 3.27 Impact Factor
[show abstract][hide abstract] ABSTRACT: The dopamine system has been linked to anhedonia in depression and both the positive and negative symptoms of schizophrenia, but it remains unclear how dopamine dysfunction could mechanistically relate to observed symptoms. There is considerable evidence that phasic dopamine signals encode prediction error (differences between expected and actual outcomes), with reinforcement learning theories being based on prediction error-mediated learning of associations. It has been hypothesized that abnormal encoding of neural prediction error signals could underlie anhedonia in depression and negative symptoms in schizophrenia by disrupting learning and blunting the salience of rewarding events, and contribute to psychotic symptoms by promoting aberrant perceptions and the formation of delusions. To test this, we used model based functional magnetic resonance imaging and an instrumental reward-learning task to investigate the neural correlates of prediction errors and expected-reward values in patients with depression (n=15), patients with schizophrenia (n=14) and healthy controls (n=17). Both patient groups exhibited abnormalities in neural prediction errors, but the spatial pattern of abnormality differed, with the degree of abnormality correlating with syndrome severity. Specifically, reduced prediction errors in the striatum and midbrain were found in depression, with the extent of signal reduction in the bilateral caudate, nucleus accumbens and midbrain correlating with increased anhedonia severity. In schizophrenia, reduced prediction error signals were observed in the caudate, thalamus, insula and amygdala-hippocampal complex, with a trend for reduced prediction errors in the midbrain, and the degree of blunting in the encoding of prediction errors in the insula, amygdala-hippocampal complex and midbrain correlating with increased severity of psychotic symptoms. Schizophrenia was also associated with disruption in the encoding of expected-reward values in the bilateral amygdala-hippocampal complex and parahippocampal gyrus, with the degree of disruption correlating with psychotic symptom severity. Neural signal abnormalities did not correlate with negative symptom severity in schizophrenia. These findings support the suggestion that a disruption in the encoding of prediction error signals contributes to anhedonia symptoms in depression. In schizophrenia, the findings support the postulate of an abnormality in error-dependent updating of inferences and beliefs driving psychotic symptoms. Phasic dopamine abnormalities in depression and schizophrenia are suggested by our observation of prediction error abnormalities in dopamine-rich brain areas, given the evidence for dopamine encoding prediction errors. The findings are consistent with proposals that psychiatric syndromes reflect different disorders of neural valuation and incentive salience formation, which helps bridge the gap between biological and phenomenological levels of understanding.
[show abstract][hide abstract] ABSTRACT: The objective of this work was to propose and demonstrate a novel technique for the assessment of tumour pharmacokinetic parameters together with a regionally estimated vascular input function. A breast cancer patient T2*-weighted dynamic contrast enhanced MRI (DCE-MRI) dataset acquired at high temporal resolution during the first-pass bolus perfusion was used for testing the technique. Extraction of the lesion volume transfer constant K(trans) together with the intravascular plasma volume fraction v(p) was achieved by optimizing a capillary input function with a measure of cardiac output using the principle of intravascular indicator dilution theory. For a region of interest drawn within the breast lesion a v(p) of 0.16 and a K(trans) of 0.70 min(-1) were estimated. Despite the value of v(p) being higher than expected, estimated K(trans) was in accordance with the literature values. In conclusion, the technique proposed here, has the main advantage of allowing the estimation of breast tumour pharmacokinetic parameters from first-pass perfusion T2*-weighted DCE-MRI data without the need of measuring an arterial input function. The technique may also have applicability to T1-weighted DCE-MRI data.
Physics in Medicine and Biology 02/2011; 56(6):1743-53. · 2.70 Impact Factor
[show abstract][hide abstract] ABSTRACT: Deficits in facial emotion processing are features of mild Alzheimer's disease (AD). These impairments are often dis-tressing for carers as well as patients. Such non-cognitive symptoms are often cited as a contributing reason for admis-sion into institutionalised care. The ability to interpret emotional cues is crucial to healthy psychological function and relationships and impaired emotional facility may lead to antisocial behavior. Understanding the origins of the non-cognitive aspects of AD may lead to an improvement in the management of sufferers and ease the carer burden. In a cross-sectional study we recorded patients' facial processing abilities, (emotion and identity recognition), disease se-verity (ADAS-cog, Neuropsychiatic Inventory) and investigated the regional cerebral blood flow correlates of facial emotion processing deficits using 99 Tc m HMPAO rCBF SPECT. Using statistical parametric mapping (SPM) we identi-fied decreased blood flow in posterior frontal regions specifically associated with emotion perception deficits and inde-pendent of non-emotional facial processing abilities or/and disease severity. The posterior frontal lobe has been identi-fied in previous studies in the absence of dementia as being important in emotion processing. The results suggest that the cognitive disease severity, in combination with the facial processing ability, do not completely explain facial emo-tion processing in AD patients and that the posterior frontal lobe mediates such behaviour.
[show abstract][hide abstract] ABSTRACT: Psychiatric neuroimaging techniques are likely to improve understanding of the brain in health and disease, but studies tend to be small, based in one imaging centre and of unclear generalisability. Multicentre studies have great appeal but face problems if functional magnetic resonance imaging (fMRI) data from different centres are to be combined. Fourteen healthy volunteers had two brain scans on different days at three scanners. Considerable effort was first made to use similar scanning sequences and standardise task implementation across centres. The n-back cognitive task was used to investigate between- and within-scanner reproducibility and reliability. Both the functional imaging and behavioural results were in good accord with the existing literature. We found no significant differences in the activation/deactivation maps between scanners, or between repeat visits to the same scanners. Between- and within-scanner reproducibility and reliability was very similar. However, the smoothness of images from the scanners differed, suggesting that smoothness equalization might further reduce inter-scanner variability. Our results for the n-back task suggest it is possible to acquire fMRI data from different scanners which allows pooling across centres, when the same field strength scanners are used and scanning sequences and paradigm implementations are standardised.
Psychiatry Research 09/2010; 184(2):86-95. · 2.46 Impact Factor
[show abstract][hide abstract] ABSTRACT: To test the prediction of survival using magnetic resonance imaging (MRI)-derived global and regional brain volumes in subjects aged 78 to 79 without dementia.
Observational follow-up study.
University teaching hospital.
Participants born in 1921, recruited in 1997/98 to a longitudinal study, who underwent brain MRI in 1999/2000.
Vital status on May 12, 2006, global and regional brain volumes.
Thirty-seven of 98 (34.9%) participants died during follow-up. After adjustment for cognitive ability at time of MRI examination, childhood intelligence, sex, hypertension, smoking history, obesity, hyperlipidemia, and age at MRI, proportion of intracranial volume occupied by the brain (brain fraction) predicted death before age 85 (P=.04). Participants with brain fraction less than 0.726 had more than twice the relative risk (2.8, 95% confidence interval=1.1-7.3) of death than participants with brain fraction greater 0.726. Lower survival was significantly associated with lower gray matter volumes in bilateral parietal and left frontoparietal areas and with lower white matter volumes in left parietal and right posterior temporal regions. Cox regression analysis showed that parietal white matter volume (P=.003), a subsequent diagnosis of dementia (P<.001), and sex (P=.004) were independent predictors of survival.
In participants aged 78 to 79, a lower global brain fraction predicted survival to approximately age 85. Smaller regional volumetric brain reductions, seen in Alzheimer's disease (AD), also predicted survival independent of dementia. The presence of prodromal AD probably explain the main findings.
Journal of the American Geriatrics Society 04/2010; 58(4):688-95. · 3.98 Impact Factor