Objectives With disease-modifying therapies in development for neurological disorders, quantitati... more Objectives With disease-modifying therapies in development for neurological disorders, quantitative brain imaging techniques become increasingly relevant for objective early diagnosis and assessment of response to treatment. The aim of this study was to evaluate the use of Brain SPECT and PET scans in the UK and explore drivers and barriers to using quantitative analysis through an online survey. Methods A web-based survey with 27 questions was used to capture a snapshot of brain imaging in the UK. The survey included multiple-choice questions assessing the availability and use of quantification for DaTscan, Perfusion SPECT, FDG PET and Amyloid PET. The survey results were reviewed and interpreted by a panel of imaging experts. Results Forty-six unique responses were collected and analysed, with 84% of responses from brain imaging sites. Within these sites, 88% perform DaTscan, 50% Perfusion SPECT, 48% FDG PET, and 33% Amyloid PET, while a few sites use other PET tracers. Quantitati...
The purpose of this study was to compare the performance of automatic detection of coronary arter... more 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 (P50.25, 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. (# 2002 Lippincott Williams & Wilkins)
Energy-weighted acquisition is a technique for reducing Compton scatter effects in nuclear medici... more Energy-weighted acquisition is a technique for reducing Compton scatter effects in nuclear medicine images. The effect of energy-weighted acquisition on SPECT99mTc images was evaluated by comparing the energy-weighted acquisition images with those obtained using a 20% photopeak energy window. Methods: SPECT images were compared using receiver operator characteristic (ROC) experiments testing the observer's ability to perform a pseudoclinical task. The tasks were detecting cold lesions within a uniform background and cold lesions within images created with a tomographic brain phantom. Results: ROC analysis for each phantom produced different results. No significant difference was found between the two acquisition techniques in detecting cold lesions on uniform backgrounds. Energy-weighted acquisition improved cold lesion detection significantly within the brain phantom in comparison with 20% photopeak acquisition. Conclusion: Lesion detection in 99mTcSPECT images can be improved using energy-weighted acquisition. This improvement, however, is dependent on the nature of the object being imaged. Images with structure show improved detection, whereas uniform images do not.
International Journal of Neural Systems, Jul 29, 2019
Models of the human brain as a complex network of interconnected sub-units are important in helpi... more Models of the human brain as a complex network of interconnected sub-units are important in helping to understand the structural basis of the clinical features of neurodegenerative disorders. The aim of this study was to characterize in a systematic manner the differences in the structural correlation networks in cortical thickness (CT) and surface area (SA) in Alzheimer's disease (AD) and behavioral variant Fronto-Temporal Dementia (bvFTD). We have used the baseline magnetic resonance imaging (MRI) data available from a large population of patients from three clinical trials in mild to moderate AD and mild bvFTD and compared this to a well-characterized healthy aging cohort. The study population comprised 202 healthy elderly subjects, 213 with bvFTD and 213 with AD. We report that both CT and SA network architecture can be described in terms of highly correlated networks whose positive and inverse links map onto the intrinsic modular organization of the four cortical lobes. The topology of the disturbance in structural network is different in the two disease conditions, and both are different from normal aging. The changes from normal are global in character and are not restricted to fronto-temporal and temporoparietal lobes, respectively, in bvFTD and AD, and indicate an increase in both global correlational strength and in particular nonhomologous inter-lobar connectivity defined by inverse correlations. These inverse correlations appear to be adaptive in character, reflecting coordinated increases in CT and SA that may compensate for corresponding impairment in functionally linked nodes. The effects were more pronounced in the cortical thickness atrophy network in bvFTD and in the surface area network in AD. Although lobar modularity is preserved in the context of neurodegenerative disease, the hub-like * Corresponding author.
Low socioeconomic status is a recognised composite measure made up of income, education and occup... more Low socioeconomic 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.
The brain's structures and functions arise from a combination of developmental processes and inte... more The brain's structures and functions arise from a combination of developmental processes and interaction with environmental experiences, beginning in utero and continuing throughout the lifespan. Broadly, the process that we think of as "successful aging" likely has its foundation in early life and is continuously shaped as life experiences are programmed into the brain in response to a changing environment. Thus, individual lifestyle choices and interventions aimed at increasing cognitive reserve and resilience could change the course of cognitive aging. To determine the relative efficacy of these approaches, we will need to understand how the timing of these interventions (e.g., age, duration, frequency) influences cognitive capacity through the lifespan. Although analysis of age-related changes in cognitive function reveal a general decline at the population level, it has become clear that there is great individual variance in the extent to which cognitive function changes with advanced age. The factors responsible for the individual differences in cognitive decline are unclear, but uncovering them with new analytical tools, epigenetic approaches, and subpopulation studies will provide a roadmap toward enhancing reserve and resilience in the population at large, and preserving cognitive function in a greater number of aging individuals. Highlights • Early-life factors, including those in utero, influence later life cognition. • However, few variables are independently associated with cognition over time. • Childhood socioeconomic status may be associated with differences in adult brains. • Preserving neurovascular health through diet and exercise may improve cognition. • Other early life factors that may contribute to late-life cognition remain unclear.
Objectives: To calculate sinus and bone graft volumes and vertical bone heights from sequential m... more 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.
Breast Cancer Research and Treatment, Mar 24, 2012
Breast cancers are evolving, multi-scale systems that are characterized by varied complex spatial... more 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.
Synopsis The cerebral reserve hypothesis proposes that the contribution of a given amount of brai... more Synopsis The cerebral reserve hypothesis proposes that the contribution of a given amount of brain pathology to intellectual decline is modified by the extent of 'cerebral reserve'. Theoretical mediators of such reserve are larger brain size and higher intellectual attainment. This study uses childhood intelligence at age 11, MR imaging and intelligence at age 79 to test the reserve hypothesis and whether this is implemented by passive (brain reserve) or active (cognitive reserve) models. The results show that head size is independent of cognitive decline whereas those with greater levels of educational and occupational attainment decline less.
unselected population. Consequently the remaining 56% of patients had either other forms of demen... more unselected population. Consequently the remaining 56% of patients had either other forms of dementia (AD, FTD, VaD) or represented the 'worried well'. Occipital hypoperfusion was demonstrated in 28% (11/39) of patients with DLB and in 31% (14/45) of non-DLB cases. Conclusion Occipital hypoperfusion on HMPAO SPECT is only demonstrated in a minority of patients with DLB. Furthermore, occipital hypoperfusion is equally likely in patients with DLB as opposed to all other dementias. It is important for reporting clinicians to be aware that the appearances of the occipital lobe on HMPAO SPECT imaging may not be sufficiently reliable to either rule in, or rule out, a diagnosis of DLB. A DaTSCAN is essential.
Journal of Magnetic Resonance Imaging, Feb 1, 1999
In vivo T1 measurements, used to monitor the uptake of contrast agent by tissues, are typically p... more In vivo T1 measurements, used to monitor the uptake of contrast agent by tissues, are typically performed as a first step in implementing compartmental analysis of contrast-enhanced breast magnetic resonance imaging (MRI) data. We have extended previously described methodology for in vivo T1 measurement (using a variable flip-angle gradient-recalled echo technique) to two-dimensional (2D), fast low-angle shot (FLASH). This approach requires computational modeling of slice-selective radiofrequency (RF) excitation to correct for nonrectangular slice profiles. The accuracy with which breast tissue T1 values can be measured by this approach is examined: T1 measurements from phantom and in vivo image data acquired with 2D and 3D FLASH imaging sequences are presented. Significant sources of error due to imaging pulse sequence quality and RF transmit field nonuniformity in the breast coil device that will have detrimental consequences for compartmental analysis are identified. Rigorous quality assurance programs with calibrated phantoms are thus recommended, to verify the accuracy with which T1 measurements are obtained.
Objectives With disease-modifying therapies in development for neurological disorders, quantitati... more Objectives With disease-modifying therapies in development for neurological disorders, quantitative brain imaging techniques become increasingly relevant for objective early diagnosis and assessment of response to treatment. The aim of this study was to evaluate the use of Brain SPECT and PET scans in the UK and explore drivers and barriers to using quantitative analysis through an online survey. Methods A web-based survey with 27 questions was used to capture a snapshot of brain imaging in the UK. The survey included multiple-choice questions assessing the availability and use of quantification for DaTscan, Perfusion SPECT, FDG PET and Amyloid PET. The survey results were reviewed and interpreted by a panel of imaging experts. Results Forty-six unique responses were collected and analysed, with 84% of responses from brain imaging sites. Within these sites, 88% perform DaTscan, 50% Perfusion SPECT, 48% FDG PET, and 33% Amyloid PET, while a few sites use other PET tracers. Quantitati...
The purpose of this study was to compare the performance of automatic detection of coronary arter... more 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 (P50.25, 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. (# 2002 Lippincott Williams & Wilkins)
Energy-weighted acquisition is a technique for reducing Compton scatter effects in nuclear medici... more Energy-weighted acquisition is a technique for reducing Compton scatter effects in nuclear medicine images. The effect of energy-weighted acquisition on SPECT99mTc images was evaluated by comparing the energy-weighted acquisition images with those obtained using a 20% photopeak energy window. Methods: SPECT images were compared using receiver operator characteristic (ROC) experiments testing the observer's ability to perform a pseudoclinical task. The tasks were detecting cold lesions within a uniform background and cold lesions within images created with a tomographic brain phantom. Results: ROC analysis for each phantom produced different results. No significant difference was found between the two acquisition techniques in detecting cold lesions on uniform backgrounds. Energy-weighted acquisition improved cold lesion detection significantly within the brain phantom in comparison with 20% photopeak acquisition. Conclusion: Lesion detection in 99mTcSPECT images can be improved using energy-weighted acquisition. This improvement, however, is dependent on the nature of the object being imaged. Images with structure show improved detection, whereas uniform images do not.
International Journal of Neural Systems, Jul 29, 2019
Models of the human brain as a complex network of interconnected sub-units are important in helpi... more Models of the human brain as a complex network of interconnected sub-units are important in helping to understand the structural basis of the clinical features of neurodegenerative disorders. The aim of this study was to characterize in a systematic manner the differences in the structural correlation networks in cortical thickness (CT) and surface area (SA) in Alzheimer's disease (AD) and behavioral variant Fronto-Temporal Dementia (bvFTD). We have used the baseline magnetic resonance imaging (MRI) data available from a large population of patients from three clinical trials in mild to moderate AD and mild bvFTD and compared this to a well-characterized healthy aging cohort. The study population comprised 202 healthy elderly subjects, 213 with bvFTD and 213 with AD. We report that both CT and SA network architecture can be described in terms of highly correlated networks whose positive and inverse links map onto the intrinsic modular organization of the four cortical lobes. The topology of the disturbance in structural network is different in the two disease conditions, and both are different from normal aging. The changes from normal are global in character and are not restricted to fronto-temporal and temporoparietal lobes, respectively, in bvFTD and AD, and indicate an increase in both global correlational strength and in particular nonhomologous inter-lobar connectivity defined by inverse correlations. These inverse correlations appear to be adaptive in character, reflecting coordinated increases in CT and SA that may compensate for corresponding impairment in functionally linked nodes. The effects were more pronounced in the cortical thickness atrophy network in bvFTD and in the surface area network in AD. Although lobar modularity is preserved in the context of neurodegenerative disease, the hub-like * Corresponding author.
Low socioeconomic status is a recognised composite measure made up of income, education and occup... more Low socioeconomic 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.
The brain's structures and functions arise from a combination of developmental processes and inte... more The brain's structures and functions arise from a combination of developmental processes and interaction with environmental experiences, beginning in utero and continuing throughout the lifespan. Broadly, the process that we think of as "successful aging" likely has its foundation in early life and is continuously shaped as life experiences are programmed into the brain in response to a changing environment. Thus, individual lifestyle choices and interventions aimed at increasing cognitive reserve and resilience could change the course of cognitive aging. To determine the relative efficacy of these approaches, we will need to understand how the timing of these interventions (e.g., age, duration, frequency) influences cognitive capacity through the lifespan. Although analysis of age-related changes in cognitive function reveal a general decline at the population level, it has become clear that there is great individual variance in the extent to which cognitive function changes with advanced age. The factors responsible for the individual differences in cognitive decline are unclear, but uncovering them with new analytical tools, epigenetic approaches, and subpopulation studies will provide a roadmap toward enhancing reserve and resilience in the population at large, and preserving cognitive function in a greater number of aging individuals. Highlights • Early-life factors, including those in utero, influence later life cognition. • However, few variables are independently associated with cognition over time. • Childhood socioeconomic status may be associated with differences in adult brains. • Preserving neurovascular health through diet and exercise may improve cognition. • Other early life factors that may contribute to late-life cognition remain unclear.
Objectives: To calculate sinus and bone graft volumes and vertical bone heights from sequential m... more 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.
Breast Cancer Research and Treatment, Mar 24, 2012
Breast cancers are evolving, multi-scale systems that are characterized by varied complex spatial... more 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.
Synopsis The cerebral reserve hypothesis proposes that the contribution of a given amount of brai... more Synopsis The cerebral reserve hypothesis proposes that the contribution of a given amount of brain pathology to intellectual decline is modified by the extent of 'cerebral reserve'. Theoretical mediators of such reserve are larger brain size and higher intellectual attainment. This study uses childhood intelligence at age 11, MR imaging and intelligence at age 79 to test the reserve hypothesis and whether this is implemented by passive (brain reserve) or active (cognitive reserve) models. The results show that head size is independent of cognitive decline whereas those with greater levels of educational and occupational attainment decline less.
unselected population. Consequently the remaining 56% of patients had either other forms of demen... more unselected population. Consequently the remaining 56% of patients had either other forms of dementia (AD, FTD, VaD) or represented the 'worried well'. Occipital hypoperfusion was demonstrated in 28% (11/39) of patients with DLB and in 31% (14/45) of non-DLB cases. Conclusion Occipital hypoperfusion on HMPAO SPECT is only demonstrated in a minority of patients with DLB. Furthermore, occipital hypoperfusion is equally likely in patients with DLB as opposed to all other dementias. It is important for reporting clinicians to be aware that the appearances of the occipital lobe on HMPAO SPECT imaging may not be sufficiently reliable to either rule in, or rule out, a diagnosis of DLB. A DaTSCAN is essential.
Journal of Magnetic Resonance Imaging, Feb 1, 1999
In vivo T1 measurements, used to monitor the uptake of contrast agent by tissues, are typically p... more In vivo T1 measurements, used to monitor the uptake of contrast agent by tissues, are typically performed as a first step in implementing compartmental analysis of contrast-enhanced breast magnetic resonance imaging (MRI) data. We have extended previously described methodology for in vivo T1 measurement (using a variable flip-angle gradient-recalled echo technique) to two-dimensional (2D), fast low-angle shot (FLASH). This approach requires computational modeling of slice-selective radiofrequency (RF) excitation to correct for nonrectangular slice profiles. The accuracy with which breast tissue T1 values can be measured by this approach is examined: T1 measurements from phantom and in vivo image data acquired with 2D and 3D FLASH imaging sequences are presented. Significant sources of error due to imaging pulse sequence quality and RF transmit field nonuniformity in the breast coil device that will have detrimental consequences for compartmental analysis are identified. Rigorous quality assurance programs with calibrated phantoms are thus recommended, to verify the accuracy with which T1 measurements are obtained.
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Papers by Roger Staff