doi: 10.3389/fnagi.2013.00045 Washout allometric reference method (WARM) for parametric analysis ... more doi: 10.3389/fnagi.2013.00045 Washout allometric reference method (WARM) for parametric analysis of [11C]PIB in human brains
PURPOSE Purpose of this study was to investigate Dual-energy CT (DECT) derived virtual non-calciu... more PURPOSE Purpose of this study was to investigate Dual-energy CT (DECT) derived virtual non-calcium (VNCa) values for absolute quantification of the bone marrow composition in the wrist. MATERIALS AND METHODS We prospectively included consecutive adult participants and examined their wrists with DECT. Ranges of VNCa and calcium values were measured in the carpal bones, radius and ulna using a semi-automatic method. Bones with bone marrow edema, assessed by two blinded radiologists, were excluded. After determining optimum parameters for the three-material decomposition, the influence of calcium values, age and sex on VNCa values was assessed using multiple linear regression. RESULTS 41 participants (Median age 53 years, range 20 years - 88 years, 51 % men) were enrolled and 399 bones assessed. At participant level mean VNCa values were -143 HU (SD 14 HU) using the current parameters for three-material decomposition and -104HU (SD 11 HU) with optimized parameters. There was a strong and significant influence of calcium values on VNCa values with the current parameters (p < 0.001, -0.137 HU[VNCa] / HU[Calcium]). With optimized parameters the calcium values and sex were not statistically significant predictors of VNCa values. Age was a significant, but clinically negligible, predictor (p = 0.03, -0.225 HU / year). CONCLUSIONS After optimizing three-material decomposition parameters, calcium values, age and sex do not substantially influence virtual non-calcium values, and DECT may therefore be used for absolute quantification of the bone marrow composition - alleviating the need for reference bones or groups.
Deep brain stimulation (DBS) in the ventral tuberal hypothalamus (VTH) is currently under investi... more Deep brain stimulation (DBS) in the ventral tuberal hypothalamus (VTH) is currently under investigation for the treatment of severe obesity. Stimulation impact on a number of closely related hypothalamic neural systems could potentially influence normal hypothalamic function and thereby generate adverse side effects. To assess the feasibility and safety of VTH DBS in a non-primate large animal model. In the VTH of 6 Göttingen minipigs, quadropolar leads were implanted bilaterally (n = 2) or unilaterally (n = 4), using optimized MRI sequences allowing identification of major diencephalic landmarks. Heart rate, weight, behavior and nighttime locomotor activity were recorded throughout the study period. Two of the unilaterally implanted minipigs were examined with [15O]H2O positron emission tomography (PET) scans performed in DBS-off and DBS-on mode. VTH DBS elicited an amplitude-dependent increase in heart rate and transient aggressive behavior. PET demonstrated that VTH DBS caused a ...
Objective: To determine whether long-term course of treated major depression has an effect on the... more Objective: To determine whether long-term course of treated major depression has an effect on the structure of the brain and the hippocampal volume. Method: An 11-year follow-up procedure was used with data collection at baseline and again at follow-up. Tensor-based morphometry (TBM) and automatic hippocampal volume measure was performed on different datasets. The baseline dataset consisted of T1-weighted magnetic resonance images (MRIs) of 24 in-patients suffering from major depression and 33 healthy controls. The second dataset consisted of T1-weighted MRIs of 31 remitted depressive patients and 36 healthy controls. The longitudinal dataset consisted of 19 patients and 19 matched healthy controls present at both the first and the second dataset. Brain segmentation and hippocampal segmentation were fully automated and were based on a spatial normalization to the International Consortium of Brain Mapping (ICBM) non-linear model. Results: Depressed patients were found to have smaller temporal lobes bilaterally, medulla and right hippocampus at baseline. However, these changes were not found at follow-up 11 years later. Moreover, these changes did not significantly correlate with the illness outcome. Conclusion: Brain structure changes seem to be state dependent in major depression, only occurring in acute episode of major depression and normalizing after remission.
ObjectiveThe main aim of the present study was to replicate a previous finding in major depressiv... more ObjectiveThe main aim of the present study was to replicate a previous finding in major depressive disorder (MDD) of association between reduced hippocampal volume and the long variant of the di- and triallelic serotonin transporter polymorphism inSLC6A4on chromosome 17q11.2. Secondarily, we also hypothesised that 5-HTTLPR may be a risk factor for MDD.MethodsQuantitative magnetic resonance imaging (MRI) of the hippocampus was studied in 23 inpatients suffering from MDD and in 33 healthy controls. Normalised volumetric MRI data of hippocampus were assessed with adjustment for total brain volume and tensor-based morphometry was used to elucidate structural brain differences. A triallelic genetic marker resulting from twoSLC6A4promoter region polymorphisms, 5-HTTLPR and rs25531, was analysed for association with MDD and quantitative traits.ResultsHealthy controls had a smaller relative hippocampal volume (relative to brain size) but a larger total brain volume compared with patients wi...
Quantitative rates of brain glucose metabolism distinguish minimally conscious from vegetative st... more Quantitative rates of brain glucose metabolism distinguish minimally conscious from vegetative state patients
Background We investigated the influence of dose, spectral separation, pitch, rotation time, and ... more Background We investigated the influence of dose, spectral separation, pitch, rotation time, and reconstruction kernel on accuracy and image noise of virtual non-calcium images using a bone marrow phantom. Methods The phantom was developed at our institution and scanned using a third-generation dual-source dual-energy CT scanner at five different spectral separations by varying the tube-voltage combinations (70 kV/Sn150 kV, 80 kV/Sn150 kV, 90 kV/Sn150 kV, and 100 kV/Sn150 kV, all with 0.6-mm tin filter [Sn]; 80 kV/140 kV without tin filter) at six different doses (volume computed tomography dose index from 1 to 80 mGy). In separate experiments, rotation times, pitch, and reconstruction kernels were varied at a constant dose and tube voltage. Accuracy was determined by measuring the mean error between virtual non-calcium values in the fluid within and outside of the bone. Image noise was defined as the standard deviation of virtual non-calcium values. Results Spectral separation, dos...
A multicenter study is under way to investigate the efficacy of allografting of embryonic mesence... more A multicenter study is under way to investigate the efficacy of allografting of embryonic mesencephalic neurons in a pig model of Parkinson's disease. We have first established that a stable parkinsonian syndrome can be established by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intoxication of adult male Göttingen minipigs. We are now using positron emission tomography (PET) methods for testing the physiological responses to MPTP intoxication and the time course of the response to several treatment strategies. We now report preliminary results obtained in 11 pigs employed in the initial phase of the study; the completed study shall ultimately include 30 pigs. Animals were randomly assigned to one of five groups: 1) Control, 2) MPTP intoxication, 3) MPTP intoxication followed by allograft, 4) MPTP intoxication followed by allograft with immunosuppression, and 5) MPTP intoxication followed by allograft with immunosuppression and co-grafting of immortalized HiB5 cells, whic...
Background: We report results of the novel Washout Allometric Reference Method (WARM) that uses e... more Background: We report results of the novel Washout Allometric Reference Method (WARM) that uses estimates of cerebral blood flow and amyloid load from the same [(11)C]Pittsburgh Compound B ([(11)C]PiB) retention maps in brain to distinguish between patients with different forms dementia, including Alzheimer's disease, and healthy volunteers. The method introduces two approaches to the identification of brain pathology related to amyloid accumulation, (1) a novel analysis of amyloid binding based on the late washout of the tracer from brain tissue, and (2) the simultaneous estimation of absolute cerebral blood flow indices (sCBF) from the early accumulation of the tracer in brain tissue. Objective: We tested the hypothesis that a change of cerebral blood flow is correlated with the degree of tracer [(11)C]PiB retention, reflecting dendritic spine pathology and consequent inhibition of brain energy metabolism and reduction of blood flow by neurovascular coupling in neurodegenerati...
Alzheimer's disease (AD) is characterized by accumulation of hyperphosphorylated tau and neurotox... more Alzheimer's disease (AD) is characterized by accumulation of hyperphosphorylated tau and neurotoxic amyloid beta protein in the brain parenchyma. Hypoxia caused by microvascular changes and disturbed capillary flows could stimulate this build-up of AD-specific proteins in the brain. In this study we compared cerebral microcirculation in a cohort of AD and MCI patients with that of age-matched controls, all without a history of diabetes or of hypertension for more than two years, using dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI). Vascular flow disturbances were quantified using a parametric model and mapped to the mid-cortical surface for group-wise statistical analysis. We found widespread hypoperfusion in patients compared to controls and identified areas of increased relative capillary transit time heterogeneity (RTH), consistent with low tissue oxygen tension. Notably, RTH was positively correlated with white matter hyperintensities and positively correlated with symptom severity in the patient cohort. These correlations extended over large parts of the temporal, parietal and frontal cortices. The results support the hypothesis of disturbed capillary flow patterns in AD and suggest that DSC-MRI may provide imaging biomarkers of impaired cerebral microcirculation in AD.
doi: 10.3389/fnagi.2013.00045 Washout allometric reference method (WARM) for parametric analysis ... more doi: 10.3389/fnagi.2013.00045 Washout allometric reference method (WARM) for parametric analysis of [11C]PIB in human brains
PURPOSE Purpose of this study was to investigate Dual-energy CT (DECT) derived virtual non-calciu... more PURPOSE Purpose of this study was to investigate Dual-energy CT (DECT) derived virtual non-calcium (VNCa) values for absolute quantification of the bone marrow composition in the wrist. MATERIALS AND METHODS We prospectively included consecutive adult participants and examined their wrists with DECT. Ranges of VNCa and calcium values were measured in the carpal bones, radius and ulna using a semi-automatic method. Bones with bone marrow edema, assessed by two blinded radiologists, were excluded. After determining optimum parameters for the three-material decomposition, the influence of calcium values, age and sex on VNCa values was assessed using multiple linear regression. RESULTS 41 participants (Median age 53 years, range 20 years - 88 years, 51 % men) were enrolled and 399 bones assessed. At participant level mean VNCa values were -143 HU (SD 14 HU) using the current parameters for three-material decomposition and -104HU (SD 11 HU) with optimized parameters. There was a strong and significant influence of calcium values on VNCa values with the current parameters (p < 0.001, -0.137 HU[VNCa] / HU[Calcium]). With optimized parameters the calcium values and sex were not statistically significant predictors of VNCa values. Age was a significant, but clinically negligible, predictor (p = 0.03, -0.225 HU / year). CONCLUSIONS After optimizing three-material decomposition parameters, calcium values, age and sex do not substantially influence virtual non-calcium values, and DECT may therefore be used for absolute quantification of the bone marrow composition - alleviating the need for reference bones or groups.
Deep brain stimulation (DBS) in the ventral tuberal hypothalamus (VTH) is currently under investi... more Deep brain stimulation (DBS) in the ventral tuberal hypothalamus (VTH) is currently under investigation for the treatment of severe obesity. Stimulation impact on a number of closely related hypothalamic neural systems could potentially influence normal hypothalamic function and thereby generate adverse side effects. To assess the feasibility and safety of VTH DBS in a non-primate large animal model. In the VTH of 6 Göttingen minipigs, quadropolar leads were implanted bilaterally (n = 2) or unilaterally (n = 4), using optimized MRI sequences allowing identification of major diencephalic landmarks. Heart rate, weight, behavior and nighttime locomotor activity were recorded throughout the study period. Two of the unilaterally implanted minipigs were examined with [15O]H2O positron emission tomography (PET) scans performed in DBS-off and DBS-on mode. VTH DBS elicited an amplitude-dependent increase in heart rate and transient aggressive behavior. PET demonstrated that VTH DBS caused a ...
Objective: To determine whether long-term course of treated major depression has an effect on the... more Objective: To determine whether long-term course of treated major depression has an effect on the structure of the brain and the hippocampal volume. Method: An 11-year follow-up procedure was used with data collection at baseline and again at follow-up. Tensor-based morphometry (TBM) and automatic hippocampal volume measure was performed on different datasets. The baseline dataset consisted of T1-weighted magnetic resonance images (MRIs) of 24 in-patients suffering from major depression and 33 healthy controls. The second dataset consisted of T1-weighted MRIs of 31 remitted depressive patients and 36 healthy controls. The longitudinal dataset consisted of 19 patients and 19 matched healthy controls present at both the first and the second dataset. Brain segmentation and hippocampal segmentation were fully automated and were based on a spatial normalization to the International Consortium of Brain Mapping (ICBM) non-linear model. Results: Depressed patients were found to have smaller temporal lobes bilaterally, medulla and right hippocampus at baseline. However, these changes were not found at follow-up 11 years later. Moreover, these changes did not significantly correlate with the illness outcome. Conclusion: Brain structure changes seem to be state dependent in major depression, only occurring in acute episode of major depression and normalizing after remission.
ObjectiveThe main aim of the present study was to replicate a previous finding in major depressiv... more ObjectiveThe main aim of the present study was to replicate a previous finding in major depressive disorder (MDD) of association between reduced hippocampal volume and the long variant of the di- and triallelic serotonin transporter polymorphism inSLC6A4on chromosome 17q11.2. Secondarily, we also hypothesised that 5-HTTLPR may be a risk factor for MDD.MethodsQuantitative magnetic resonance imaging (MRI) of the hippocampus was studied in 23 inpatients suffering from MDD and in 33 healthy controls. Normalised volumetric MRI data of hippocampus were assessed with adjustment for total brain volume and tensor-based morphometry was used to elucidate structural brain differences. A triallelic genetic marker resulting from twoSLC6A4promoter region polymorphisms, 5-HTTLPR and rs25531, was analysed for association with MDD and quantitative traits.ResultsHealthy controls had a smaller relative hippocampal volume (relative to brain size) but a larger total brain volume compared with patients wi...
Quantitative rates of brain glucose metabolism distinguish minimally conscious from vegetative st... more Quantitative rates of brain glucose metabolism distinguish minimally conscious from vegetative state patients
Background We investigated the influence of dose, spectral separation, pitch, rotation time, and ... more Background We investigated the influence of dose, spectral separation, pitch, rotation time, and reconstruction kernel on accuracy and image noise of virtual non-calcium images using a bone marrow phantom. Methods The phantom was developed at our institution and scanned using a third-generation dual-source dual-energy CT scanner at five different spectral separations by varying the tube-voltage combinations (70 kV/Sn150 kV, 80 kV/Sn150 kV, 90 kV/Sn150 kV, and 100 kV/Sn150 kV, all with 0.6-mm tin filter [Sn]; 80 kV/140 kV without tin filter) at six different doses (volume computed tomography dose index from 1 to 80 mGy). In separate experiments, rotation times, pitch, and reconstruction kernels were varied at a constant dose and tube voltage. Accuracy was determined by measuring the mean error between virtual non-calcium values in the fluid within and outside of the bone. Image noise was defined as the standard deviation of virtual non-calcium values. Results Spectral separation, dos...
A multicenter study is under way to investigate the efficacy of allografting of embryonic mesence... more A multicenter study is under way to investigate the efficacy of allografting of embryonic mesencephalic neurons in a pig model of Parkinson's disease. We have first established that a stable parkinsonian syndrome can be established by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intoxication of adult male Göttingen minipigs. We are now using positron emission tomography (PET) methods for testing the physiological responses to MPTP intoxication and the time course of the response to several treatment strategies. We now report preliminary results obtained in 11 pigs employed in the initial phase of the study; the completed study shall ultimately include 30 pigs. Animals were randomly assigned to one of five groups: 1) Control, 2) MPTP intoxication, 3) MPTP intoxication followed by allograft, 4) MPTP intoxication followed by allograft with immunosuppression, and 5) MPTP intoxication followed by allograft with immunosuppression and co-grafting of immortalized HiB5 cells, whic...
Background: We report results of the novel Washout Allometric Reference Method (WARM) that uses e... more Background: We report results of the novel Washout Allometric Reference Method (WARM) that uses estimates of cerebral blood flow and amyloid load from the same [(11)C]Pittsburgh Compound B ([(11)C]PiB) retention maps in brain to distinguish between patients with different forms dementia, including Alzheimer's disease, and healthy volunteers. The method introduces two approaches to the identification of brain pathology related to amyloid accumulation, (1) a novel analysis of amyloid binding based on the late washout of the tracer from brain tissue, and (2) the simultaneous estimation of absolute cerebral blood flow indices (sCBF) from the early accumulation of the tracer in brain tissue. Objective: We tested the hypothesis that a change of cerebral blood flow is correlated with the degree of tracer [(11)C]PiB retention, reflecting dendritic spine pathology and consequent inhibition of brain energy metabolism and reduction of blood flow by neurovascular coupling in neurodegenerati...
Alzheimer's disease (AD) is characterized by accumulation of hyperphosphorylated tau and neurotox... more Alzheimer's disease (AD) is characterized by accumulation of hyperphosphorylated tau and neurotoxic amyloid beta protein in the brain parenchyma. Hypoxia caused by microvascular changes and disturbed capillary flows could stimulate this build-up of AD-specific proteins in the brain. In this study we compared cerebral microcirculation in a cohort of AD and MCI patients with that of age-matched controls, all without a history of diabetes or of hypertension for more than two years, using dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI). Vascular flow disturbances were quantified using a parametric model and mapped to the mid-cortical surface for group-wise statistical analysis. We found widespread hypoperfusion in patients compared to controls and identified areas of increased relative capillary transit time heterogeneity (RTH), consistent with low tissue oxygen tension. Notably, RTH was positively correlated with white matter hyperintensities and positively correlated with symptom severity in the patient cohort. These correlations extended over large parts of the temporal, parietal and frontal cortices. The results support the hypothesis of disturbed capillary flow patterns in AD and suggest that DSC-MRI may provide imaging biomarkers of impaired cerebral microcirculation in AD.
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