To compare daytime intraduodenal levodopa/carbidopa infusion as monotherapy with individually opt... more To compare daytime intraduodenal levodopa/carbidopa infusion as monotherapy with individually optimized conventional combination therapies in patients with advanced Parkinson disease (PD) for motor fluctuations and quality of life (QoL). Methods: Twenty-four patients with motor fluctuations and dyskinesia were studied in a randomized crossover design to compare individualized conventional treatment and intraduodenal infusion of a levodopa/ carbidopa gel for 3 ϩ 3 weeks. Video scoring of motor function was assessed by blinded assessors on a global Treatment Response Scale from Ϫ3 to 0 to ϩ3 (from severe "off" to "on" to "on" with severe dyskinesia). Patient self-assessment of motor performance and QoL was done using an electronic diary. Results: Median percentage of ratings in a functional "on" interval (Ϫ1 to ϩ1) was increased from 81 to 100% by infusion therapy (p Ͻ 0.01). This improvement was accompanied by a decrease in "off" state (p Ͻ 0.01) and no increase in dyskinesia. Median Unified Parkinson's Disease Rating Scale score decreased from 53 to 35 in favor of infusion (p Ͻ 0.05). QoL was improved, using the two instruments: Parkinson's Disease Questionnaire-39 and 15D Quality of Life Instrument (p Ͻ 0.01). Adverse events were similar for both treatment strategies. Conclusions: Continuous intraduodenal infusion of the levodopa/carbidopa enteral gel as monotherapy is safe and clinically superior to a number of individually optimized combinations of conventional oral and subcutaneous medications in patients with motor fluctuations. Intraduodenal infusion of levodopa offers an important alternative in treating patients with advanced Parkinson disease.
Levodopa-entacapone-carbidopa intestinal gel (LECIG) provides continuous drug delivery through in... more Levodopa-entacapone-carbidopa intestinal gel (LECIG) provides continuous drug delivery through intrajejunal infusion. The aim of this study was to characterize the population pharmacokinetics of levodopa following LECIG and levodopa-carbidopa intestinal gel (LCIG) infusion to investigate suitable translation of dose from LCIG to LECIG treatment, and the impact of common variations in the dopa-decarboxylase (DDC) and catechol-O-methyltransferase (COMT) genes on levodopa pharmacokinetics. A non-linear mixed-effects model of levodopa pharmacokinetics was developed using plasma concentration data from a double-blind, cross-over study of LCIG compared with LECIG in patients with advanced Parkinson’s disease (n = 11). All patients were genotyped for rs4680 (polymorphism of the COMT gene), rs921451 and rs3837091 (polymorphisms of the DDC gene). The final model was a one compartment model with a high fixed absorption rate constant, and a first order elimination, with estimated apparent clea...
Levodopa is the most effective symptomatic treatment throughout the course of Parkinson's dis... more Levodopa is the most effective symptomatic treatment throughout the course of Parkinson's disease, but as the disease progresses, there may be a need for individualized, fine‐tuned treatments.
To evaluate the safety and tolerability of the T-Port(®) for intestinal infusion of levodopa/carb... more To evaluate the safety and tolerability of the T-Port(®) for intestinal infusion of levodopa/carbidopa gel in patients with advanced Parkinson's disease (PD). This prospective study was carried out in 24 patients with PD (15 males, mean age 61.8 years, mean duration PD 18.7 years). All adverse device effects were evaluated at 2 weeks, 3 months and 6 months and until explantation or death. Post-operative complications were similar to endoscopic gastrojejunostomy placement (four peritoneal irritation, one pocket pain). Eight patients with prior experience with the endoscopic gastrojejunostomy preferred the T-Port. The total device experience was 83.6 years, and the average survival time was 3.6 (range 1.1-5.2) years. Six T-Ports were still in use, and two patients had died due to non-device-related reasons. Sixteen T-Ports had been explanted due to 15 stoma reactions (14 inflammations and one infection) and one tilting of the T-Port. The T-Ports were replaced with endoscopic gastr...
Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 2015
In idiopathic Parkinson disease and atypical parkinsonian disorders, central dopaminergic and ove... more In idiopathic Parkinson disease and atypical parkinsonian disorders, central dopaminergic and overall brain functional activity are altered to different degrees, causing difficulties in achieving an unambiguous clinical diagnosis. A dual examination using (123)I-FP-CIT ((123)I-N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane, or (123)I-ioflupane) SPECT and(18)F-FDG PET provides complementary information on dopamine transporter (DAT) availability and overall brain functional activity, respectively. Parametric images based on a single, dynamic (11)C-PE2I (N-(3-iodoprop-2E-enyl)-2β-carbomethoxy-3β-(4-methyl-phenyl)nortropane) scan potentially supply both DAT availability (nondisplaceable binding potential [BPND]) and relative cerebral blood flow (relative delivery [R1]) at voxel level. This study aimed to evaluate the validity of (11)C-PE2I PET against the dual-modality approach using (123)I-FP-CIT SPECT and (18)F-FDG PET. Sixteen patients with parkinsonian disorders had a ...
A new concept for individualising the dosage of drugs in solid form is presented. The principle i... more A new concept for individualising the dosage of drugs in solid form is presented. The principle is based on the use of standardised units (microtablets), each containing a subtherapeutic amount of the active ingredient. The required dose is fine-tuned by counting out a specific number of these units. The microtablets are counted electronically from the attached cassette by the automatic dispensing device. The individual dose is set and the dispenser counts and delivers the correct number of microtablets. The usefulness of the automatic dispenser concept and acceptability of the apparatus were evaluated in patients with Parkinson's disease (PD). After initial instruction on use of the dispenser, 20 patients operated it themselves. All patients were generally satisfied with their management of the automatic dispenser and most would be happy to use the device again. Further technical development is required before use in clinical practice, but the current prototype may be acceptable for some patients. It is concluded that the final version of the automatic dose dispenser concept will offer potential for improvement of drug administration for patients with PD or other diseases requiring individual dosage.
Two methods for distinguishing between healthy controls and patients diagnosed with Parkinson’s d... more Two methods for distinguishing between healthy controls and patients diagnosed with Parkinson’s disease by means of recorded smooth pursuit eye movements are presented and evaluated. Both methods are based on the principles of stochastic anomaly detection and make use of orthogonal series approximation for probability distribution estimation. The first method relies on the identification of a Wiener model of the smooth pursuit system and attempts to find statistically significant differences between the estimated parameters in healthy controls and patients with Parkinson’s disease. The second method applies the same statistical method to distinguish between the gaze trajectories of healthy and Parkinson subjects tracking visual stimuli. Both methods show promising results, where healthy controls and patients with Parkinson’s disease are effectively separated in terms of the considered metric. The results are preliminary because of the small number of participating test subjects, but they are indicative of the potential of the presented methods as diagnosing or staging tools for Parkinson’s disease.
2014 18th International Conference on Information Visualisation, 2014
Patients with Parkinson's disease (PD) need to be frequently monitored in order to assess the... more Patients with Parkinson's disease (PD) need to be frequently monitored in order to assess their individual symptoms and treatment-related complications. Advances in technology have introduced telemedicine for patients in remote locations. However, data produced in such settings lack much information and are not easy to analyze or interpret compared to traditional, direct contact between the patient and clinician. Therefore, there is a need to present the data using visualization techniques in order to communicate in an understandable and objective manner to the clinician. This paper presents interaction and visualization approaches used to aid clinicians in the analysis of repeated measures of spirography of PD patients gathered by means of a telemetry touch screen device. The proposed approach enables clinicians to observe fine motor impairments and identify motor fluctuations of their patients while they perform the tests from their homes using the telemetry device.
Two studies comparing intraduodenal infusion of a levodopa/carbidopa gel with oral treatments in ... more Two studies comparing intraduodenal infusion of a levodopa/carbidopa gel with oral treatments in advanced PD patients demonstrated improvement in UPDRS scores and in frequent clinical ratings on a global treatment response scale. Further analysis of data from these studies was performed to find predictive factors related to degree of improvement with infusion. Pearson's correlation coefficients between measures of improvement and baseline variables were calculated. Using data from one study, a prediction model was designed and was then evaluated using the other study's data. Correlations were found indicating that patients with more severe symptoms at baseline were most improved after infusion.
Control of movement depends on the continuous release of dopamine by neurons in the basal ganglia... more Control of movement depends on the continuous release of dopamine by neurons in the basal ganglia of the brain. The degeneration of these neurons in Parkinson's disease (PD) interferes with the flow of dopamine, leading to classic motor symptoms. In early PD, enough dopaminergic neurons remain to store dopamine provided by periodic dosing with oral levodopa and relatively normal, tonic levels of dopamine release are maintained. PD progression leads to degeneration of remaining dopaminergic terminals and loss of buffering capacity for exogenous levodopa. As a result, there are supraphysiological levels of dopamine after dosing and troughs when the available dopamine has been depleted. These divergent levels are associated with dyskinesia and 'off' states, respectively. Treatment strategies that provide a continuous flow of dopamine and can thus mimic normal physiological dopamine stimulation have potential to improve motor control for patients with advanced PD.
The mean spiral score differed significantly across the three self-assessed motor states (p<0.001... more The mean spiral score differed significantly across the three self-assessed motor states (p<0.001, ANOVA test). Tukey post-hoc comparisons indicate that the mean spiral score (mean ± SD; [95% CI for mean]) in DYS state (5.2 ± 1.8; [5.12, 5.28]) was higher than the mean spiral score in OFF (4.3 ± 1.7; [4.22, 4.37]) and ON (4.2 ± 1.7; [4.17, 4.29]) states (Fig 2). The mean spiral score was also significantly different among individual TRS values of slightly 'off' (4.02 ± 1.63), 'on' (4.07 ± 1.65) and slightly 'dyskinetic' (4.6 ± 1.71), (p<0.001). There were no differences in drawing completion times among the three motor states (p=0.509). In the OFF and ON states, patients drew slightly more impaired spirals in the afternoon whereas in the DYS state the spiral drawing performance was more impaired in the morning (Fig 3).
More than 30 years after its development, levodopa is still the most effective treatment for the ... more More than 30 years after its development, levodopa is still the most effective treatment for the symptomatic control of Parkinson&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease (PD). Although a number of therapies have been developed in an attempt to improve PD management, such as dopaminergic agonists and inhibitors of COMT and MAO-B, most patients still depend on levodopa alone because of its superior ability to control PD symptoms. The issue of toxicity has been raised by in vitro studies suggesting that levodopa might be toxic to dopaminergic neurons, but this has since been answered by in vivo studies finding no evidence of toxicity and possibly even neurotrophic-like effects. A more pressing concern regarding levodopa is its association with the development of motor complications after long-term use. Pulsatile dopaminergic stimulation as a result of erratic absorption and the short half-life of levodopa have been central issues in attempts to explain this occurrence. Evidence suggests that altering the delivery of levodopa to provide a more continuous supply of this drug to the brain may result in improved control of PD symptoms.
The radioligand [(11)C]PE2I is highly selective for dopamine transporter (DAT) and can be used in... more The radioligand [(11)C]PE2I is highly selective for dopamine transporter (DAT) and can be used in vivo for investigation of changes in DAT concentration, progression of disease and validation of treatment using positron emission tomography (PET). DAT is an important protein for regulation of central dopamine concentration and DAT deficiency has been associated with several neurodegenerative and neuropsychiatric disorders. Accurate parametric images are a prerequisite for clinical application of [(11)C]PE2I. The purpose of this study was to evaluate different methods for producing [(11)C]PE2I parametric images, showing binding potential (BPND) and relative delivery (R1) at the voxel level, using clinical data as well as simulations. Investigations were made in twelve subjects either with social anxiety disorder (n=6) or parkinsonian syndrome (n=6), each receiving an 80 min dynamic PET scan. All subjects underwent a T1-weighted MRI scan which was co-registered to the PET images and used for definition of regions of interest using a probabilistic template (PVElab). Two basis function implementations (receptor parametric mapping: RPM, RPM2) of the simplified reference tissue model (SRTM) and three multilinear reference tissue models (MRTMo, MRTM and MRTM2) were used for computation of parametric BPND and R1 images. In addition, reference Logan and standard uptake value ratio (SUVr) were investigated. Evaluations of BPND and R1 images were performed using linear regression to compare the parametric methods to region-based analyses with SRTM and cerebellar gray matter as reference region. Accuracy and precision of each method were assessed by simulations. Correlation and slope of linear regression between parametric and region-based BPND and R1 values in both striatum and extra-striatal regions were optimal for RPM (R(2)=0.99 for both BPND and R1; slopes 0.99 and 0.98 for BPND and R1, respectively, in striatum). In addition, accuracy and precision were best for RPM and RPM2. The basis function methods provided more robust estimations of the parameters compared to the other models and performed best in simulations. RPM, a basis function implementation of SRTM, is the preferred method for voxel level analysis of [(11)C]PE2I PET studies.
To compare daytime intraduodenal levodopa/carbidopa infusion as monotherapy with individually opt... more To compare daytime intraduodenal levodopa/carbidopa infusion as monotherapy with individually optimized conventional combination therapies in patients with advanced Parkinson disease (PD) for motor fluctuations and quality of life (QoL). Methods: Twenty-four patients with motor fluctuations and dyskinesia were studied in a randomized crossover design to compare individualized conventional treatment and intraduodenal infusion of a levodopa/ carbidopa gel for 3 ϩ 3 weeks. Video scoring of motor function was assessed by blinded assessors on a global Treatment Response Scale from Ϫ3 to 0 to ϩ3 (from severe "off" to "on" to "on" with severe dyskinesia). Patient self-assessment of motor performance and QoL was done using an electronic diary. Results: Median percentage of ratings in a functional "on" interval (Ϫ1 to ϩ1) was increased from 81 to 100% by infusion therapy (p Ͻ 0.01). This improvement was accompanied by a decrease in "off" state (p Ͻ 0.01) and no increase in dyskinesia. Median Unified Parkinson's Disease Rating Scale score decreased from 53 to 35 in favor of infusion (p Ͻ 0.05). QoL was improved, using the two instruments: Parkinson's Disease Questionnaire-39 and 15D Quality of Life Instrument (p Ͻ 0.01). Adverse events were similar for both treatment strategies. Conclusions: Continuous intraduodenal infusion of the levodopa/carbidopa enteral gel as monotherapy is safe and clinically superior to a number of individually optimized combinations of conventional oral and subcutaneous medications in patients with motor fluctuations. Intraduodenal infusion of levodopa offers an important alternative in treating patients with advanced Parkinson disease.
Levodopa-entacapone-carbidopa intestinal gel (LECIG) provides continuous drug delivery through in... more Levodopa-entacapone-carbidopa intestinal gel (LECIG) provides continuous drug delivery through intrajejunal infusion. The aim of this study was to characterize the population pharmacokinetics of levodopa following LECIG and levodopa-carbidopa intestinal gel (LCIG) infusion to investigate suitable translation of dose from LCIG to LECIG treatment, and the impact of common variations in the dopa-decarboxylase (DDC) and catechol-O-methyltransferase (COMT) genes on levodopa pharmacokinetics. A non-linear mixed-effects model of levodopa pharmacokinetics was developed using plasma concentration data from a double-blind, cross-over study of LCIG compared with LECIG in patients with advanced Parkinson’s disease (n = 11). All patients were genotyped for rs4680 (polymorphism of the COMT gene), rs921451 and rs3837091 (polymorphisms of the DDC gene). The final model was a one compartment model with a high fixed absorption rate constant, and a first order elimination, with estimated apparent clea...
Levodopa is the most effective symptomatic treatment throughout the course of Parkinson's dis... more Levodopa is the most effective symptomatic treatment throughout the course of Parkinson's disease, but as the disease progresses, there may be a need for individualized, fine‐tuned treatments.
To evaluate the safety and tolerability of the T-Port(®) for intestinal infusion of levodopa/carb... more To evaluate the safety and tolerability of the T-Port(®) for intestinal infusion of levodopa/carbidopa gel in patients with advanced Parkinson's disease (PD). This prospective study was carried out in 24 patients with PD (15 males, mean age 61.8 years, mean duration PD 18.7 years). All adverse device effects were evaluated at 2 weeks, 3 months and 6 months and until explantation or death. Post-operative complications were similar to endoscopic gastrojejunostomy placement (four peritoneal irritation, one pocket pain). Eight patients with prior experience with the endoscopic gastrojejunostomy preferred the T-Port. The total device experience was 83.6 years, and the average survival time was 3.6 (range 1.1-5.2) years. Six T-Ports were still in use, and two patients had died due to non-device-related reasons. Sixteen T-Ports had been explanted due to 15 stoma reactions (14 inflammations and one infection) and one tilting of the T-Port. The T-Ports were replaced with endoscopic gastr...
Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 2015
In idiopathic Parkinson disease and atypical parkinsonian disorders, central dopaminergic and ove... more In idiopathic Parkinson disease and atypical parkinsonian disorders, central dopaminergic and overall brain functional activity are altered to different degrees, causing difficulties in achieving an unambiguous clinical diagnosis. A dual examination using (123)I-FP-CIT ((123)I-N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane, or (123)I-ioflupane) SPECT and(18)F-FDG PET provides complementary information on dopamine transporter (DAT) availability and overall brain functional activity, respectively. Parametric images based on a single, dynamic (11)C-PE2I (N-(3-iodoprop-2E-enyl)-2β-carbomethoxy-3β-(4-methyl-phenyl)nortropane) scan potentially supply both DAT availability (nondisplaceable binding potential [BPND]) and relative cerebral blood flow (relative delivery [R1]) at voxel level. This study aimed to evaluate the validity of (11)C-PE2I PET against the dual-modality approach using (123)I-FP-CIT SPECT and (18)F-FDG PET. Sixteen patients with parkinsonian disorders had a ...
A new concept for individualising the dosage of drugs in solid form is presented. The principle i... more A new concept for individualising the dosage of drugs in solid form is presented. The principle is based on the use of standardised units (microtablets), each containing a subtherapeutic amount of the active ingredient. The required dose is fine-tuned by counting out a specific number of these units. The microtablets are counted electronically from the attached cassette by the automatic dispensing device. The individual dose is set and the dispenser counts and delivers the correct number of microtablets. The usefulness of the automatic dispenser concept and acceptability of the apparatus were evaluated in patients with Parkinson&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease (PD). After initial instruction on use of the dispenser, 20 patients operated it themselves. All patients were generally satisfied with their management of the automatic dispenser and most would be happy to use the device again. Further technical development is required before use in clinical practice, but the current prototype may be acceptable for some patients. It is concluded that the final version of the automatic dose dispenser concept will offer potential for improvement of drug administration for patients with PD or other diseases requiring individual dosage.
Two methods for distinguishing between healthy controls and patients diagnosed with Parkinson’s d... more Two methods for distinguishing between healthy controls and patients diagnosed with Parkinson’s disease by means of recorded smooth pursuit eye movements are presented and evaluated. Both methods are based on the principles of stochastic anomaly detection and make use of orthogonal series approximation for probability distribution estimation. The first method relies on the identification of a Wiener model of the smooth pursuit system and attempts to find statistically significant differences between the estimated parameters in healthy controls and patients with Parkinson’s disease. The second method applies the same statistical method to distinguish between the gaze trajectories of healthy and Parkinson subjects tracking visual stimuli. Both methods show promising results, where healthy controls and patients with Parkinson’s disease are effectively separated in terms of the considered metric. The results are preliminary because of the small number of participating test subjects, but they are indicative of the potential of the presented methods as diagnosing or staging tools for Parkinson’s disease.
2014 18th International Conference on Information Visualisation, 2014
Patients with Parkinson's disease (PD) need to be frequently monitored in order to assess the... more Patients with Parkinson's disease (PD) need to be frequently monitored in order to assess their individual symptoms and treatment-related complications. Advances in technology have introduced telemedicine for patients in remote locations. However, data produced in such settings lack much information and are not easy to analyze or interpret compared to traditional, direct contact between the patient and clinician. Therefore, there is a need to present the data using visualization techniques in order to communicate in an understandable and objective manner to the clinician. This paper presents interaction and visualization approaches used to aid clinicians in the analysis of repeated measures of spirography of PD patients gathered by means of a telemetry touch screen device. The proposed approach enables clinicians to observe fine motor impairments and identify motor fluctuations of their patients while they perform the tests from their homes using the telemetry device.
Two studies comparing intraduodenal infusion of a levodopa/carbidopa gel with oral treatments in ... more Two studies comparing intraduodenal infusion of a levodopa/carbidopa gel with oral treatments in advanced PD patients demonstrated improvement in UPDRS scores and in frequent clinical ratings on a global treatment response scale. Further analysis of data from these studies was performed to find predictive factors related to degree of improvement with infusion. Pearson&#39;s correlation coefficients between measures of improvement and baseline variables were calculated. Using data from one study, a prediction model was designed and was then evaluated using the other study&#39;s data. Correlations were found indicating that patients with more severe symptoms at baseline were most improved after infusion.
Control of movement depends on the continuous release of dopamine by neurons in the basal ganglia... more Control of movement depends on the continuous release of dopamine by neurons in the basal ganglia of the brain. The degeneration of these neurons in Parkinson&amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease (PD) interferes with the flow of dopamine, leading to classic motor symptoms. In early PD, enough dopaminergic neurons remain to store dopamine provided by periodic dosing with oral levodopa and relatively normal, tonic levels of dopamine release are maintained. PD progression leads to degeneration of remaining dopaminergic terminals and loss of buffering capacity for exogenous levodopa. As a result, there are supraphysiological levels of dopamine after dosing and troughs when the available dopamine has been depleted. These divergent levels are associated with dyskinesia and &amp;amp;amp;amp;amp;amp;amp;amp;#39;off&amp;amp;amp;amp;amp;amp;amp;amp;#39; states, respectively. Treatment strategies that provide a continuous flow of dopamine and can thus mimic normal physiological dopamine stimulation have potential to improve motor control for patients with advanced PD.
The mean spiral score differed significantly across the three self-assessed motor states (p<0.001... more The mean spiral score differed significantly across the three self-assessed motor states (p<0.001, ANOVA test). Tukey post-hoc comparisons indicate that the mean spiral score (mean ± SD; [95% CI for mean]) in DYS state (5.2 ± 1.8; [5.12, 5.28]) was higher than the mean spiral score in OFF (4.3 ± 1.7; [4.22, 4.37]) and ON (4.2 ± 1.7; [4.17, 4.29]) states (Fig 2). The mean spiral score was also significantly different among individual TRS values of slightly 'off' (4.02 ± 1.63), 'on' (4.07 ± 1.65) and slightly 'dyskinetic' (4.6 ± 1.71), (p<0.001). There were no differences in drawing completion times among the three motor states (p=0.509). In the OFF and ON states, patients drew slightly more impaired spirals in the afternoon whereas in the DYS state the spiral drawing performance was more impaired in the morning (Fig 3).
More than 30 years after its development, levodopa is still the most effective treatment for the ... more More than 30 years after its development, levodopa is still the most effective treatment for the symptomatic control of Parkinson&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease (PD). Although a number of therapies have been developed in an attempt to improve PD management, such as dopaminergic agonists and inhibitors of COMT and MAO-B, most patients still depend on levodopa alone because of its superior ability to control PD symptoms. The issue of toxicity has been raised by in vitro studies suggesting that levodopa might be toxic to dopaminergic neurons, but this has since been answered by in vivo studies finding no evidence of toxicity and possibly even neurotrophic-like effects. A more pressing concern regarding levodopa is its association with the development of motor complications after long-term use. Pulsatile dopaminergic stimulation as a result of erratic absorption and the short half-life of levodopa have been central issues in attempts to explain this occurrence. Evidence suggests that altering the delivery of levodopa to provide a more continuous supply of this drug to the brain may result in improved control of PD symptoms.
The radioligand [(11)C]PE2I is highly selective for dopamine transporter (DAT) and can be used in... more The radioligand [(11)C]PE2I is highly selective for dopamine transporter (DAT) and can be used in vivo for investigation of changes in DAT concentration, progression of disease and validation of treatment using positron emission tomography (PET). DAT is an important protein for regulation of central dopamine concentration and DAT deficiency has been associated with several neurodegenerative and neuropsychiatric disorders. Accurate parametric images are a prerequisite for clinical application of [(11)C]PE2I. The purpose of this study was to evaluate different methods for producing [(11)C]PE2I parametric images, showing binding potential (BPND) and relative delivery (R1) at the voxel level, using clinical data as well as simulations. Investigations were made in twelve subjects either with social anxiety disorder (n=6) or parkinsonian syndrome (n=6), each receiving an 80 min dynamic PET scan. All subjects underwent a T1-weighted MRI scan which was co-registered to the PET images and used for definition of regions of interest using a probabilistic template (PVElab). Two basis function implementations (receptor parametric mapping: RPM, RPM2) of the simplified reference tissue model (SRTM) and three multilinear reference tissue models (MRTMo, MRTM and MRTM2) were used for computation of parametric BPND and R1 images. In addition, reference Logan and standard uptake value ratio (SUVr) were investigated. Evaluations of BPND and R1 images were performed using linear regression to compare the parametric methods to region-based analyses with SRTM and cerebellar gray matter as reference region. Accuracy and precision of each method were assessed by simulations. Correlation and slope of linear regression between parametric and region-based BPND and R1 values in both striatum and extra-striatal regions were optimal for RPM (R(2)=0.99 for both BPND and R1; slopes 0.99 and 0.98 for BPND and R1, respectively, in striatum). In addition, accuracy and precision were best for RPM and RPM2. The basis function methods provided more robust estimations of the parameters compared to the other models and performed best in simulations. RPM, a basis function implementation of SRTM, is the preferred method for voxel level analysis of [(11)C]PE2I PET studies.
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Papers by D. Nyholm