89 research outputs found
Diagnostic performance of the specific uptake size index for semi-quantitative analysis of I-123-FP-CIT SPECT: harmonized multi-center research setting versus typical clinical single-camera setting
Introduction: The specific uptake size index (SUSI) of striatal FP-CIT uptake is independent of spatial resolution in the SPECT image, in contrast to the specific binding ratio (SBR). This suggests that the SUSI is particularly appropriate for multi-site/multi-camera settings in which camera-specific effects increase inter-subject variability of spatial resolution. However, the SUSI is sensitive to inter-subject variability of striatum size. Furthermore, it might be
more sensitive to errors of the estimate of non-displaceable FP-CIT binding. This study compared SUSI and SBR in the multi-site/multi-camera (MULTI) setting of a prospective multi-center study and in a mono-site/mono-camera (MONO) setting representative of clinical routine.
Methods: The MULTI setting included patients with Parkinson’s disease (PD, n = 438) and healthy controls (n = 207) from the Parkinson Progression Marker Initiative. The MONO setting included 122 patients from routine clinical patient care in whom FP-CIT SPECT had been performed with the same double-head SPECT system according to the same acquisition and reconstruction protocol. Patients were categorized as “neurodegenerative” (n = 84) or “non-neurodegenerative” (n = 38) based on follow-up data. FP-CIT SPECTs were stereotactically normalized to MNI space. SUSI and SBR were computed for caudate, putamen, and whole striatum using unilateral ROIs predefined in MNI space. SUSI analysis was repeated in native patient space in the MONO setting. The area (AUC) under the ROC
curve for identification of PD/“neurodegenerative” cases was used as performance measure.
Results: In both settings, the highest AUC was achieved by the putamen (minimum over both hemispheres), independent of the semi-quantitative method (SUSI or SBR). The putaminal SUSI provided slightly better performance with ROI analysis in MNI space compared to patient space (AUC = 0.969 vs. 0.961, p = 0.129). The SUSI (computed in MNI space) performed slightly better than the SBR in the MULTI setting (AUC = 0.993 vs. 0.991, p = 0.
207) and slightly worse in the MONO setting (AUC = 0.969 vs. AUC = 0.976, p = 0.259). There was a trend toward larger AUC difference between SUSI and SBR in the MULTI setting compared to the MONO setting (p = 0.073). Variability of voxel intensity in the reference region was larger in misclassified cases compared to correctly classified cases for both SUSI and SBR (MULTI setting: p = 0.007 and p = 0.012, respectively).
Conclusions: The SUSI is particularly useful in MULTI settings. SPECT images should be stereotactically normalized prior to SUSI analysis. The putaminal SUSI provides better diagnostic performance than the SUSI of the whole striatum. Errors of the estimate of non-displaceable count density in the reference region can cause misclassification by both SUSI and SBR, particularly in borderline cases. These cases might be identified by visual checking FP-CIT uptake in the reference region for particularly high variability
Impact of the size of the normal database on the performance of the specific binding ratio in dopamine transporter SPECT
Background: This study investigated the impact of the size of the normal database on the classification performance of the specific binding ratio (SBR) in dopamine transporter (DAT) SPECT with [123I]FP-CIT in different settings.
Methods: The first subject sample comprised 645 subjects from the Parkinson's Progression Marker Initiative (PPMI), 207 healthy controls (HC), and 438 Parkinson's disease (PD) patients. The second sample comprised 372 patients from clinical routine patient care, 186 with non-neurodegenerative parkinsonian syndrome (PS) and 186 with neurodegenerative PS. Single-photon emission computed tomography (SPECT) images of the clinical sample were reconstructed with two different reconstruction algorithms (filtered backprojection, iterative ordered subsets expectation maximization (OSEM) reconstruction with resolution recovery). The putaminal specific binding ratio (SBR) was computed using an anatomical region of interest (ROI) predefined in standard (MNI) space in the Automated Anatomic Labeling (AAL) atlas or using hottest voxels (HV) analysis in large predefined ROIs. SBR values were transformed to z-scores using mean and standard deviation of the SBR in a normal database of varying sizes (n = 5, 10, 15,…, 50) randomly selected from the HC subjects (PPMI sample) or the patients with non-neurodegenerative PS (clinical sample). Accuracy, sensitivity, and specificity for identifying patients with PD or neurodegenerative PS were determined as performance measures using a predefined fixed cutoff on the z-score. This was repeated for 10,000 randomly selected normal databases, separately for each size of the normal database. Mean and 5th percentile of the performance measures over the 10,000 realizations were computed. Accuracy, sensitivity, and specificity when using the whole set of HC or non-neurodegenerative PS subjects as normal database were used as benchmark.
Results: Mean loss of accuracy of the putamen SBR z-score was below 1% when the normal database included at least 15 subjects, independent of subject sample (PPMI or clinical), reconstruction method (filtered backprojection or OSEM), and ROI method (AAL or HV). However, the variability of the accuracy of the putamen SBR z-score decreased monotonically with increasing size of normal database and was still considerable at size 15. In order to achieve less than 5% "maximum" loss of accuracy (defined by the 5th percentile) in all settings required at least 25 to 30 subjects in the normal database. Reduction of mean and "maximum" loss of accuracy of the putamen SBR z-score by further increasing the size of the normal database was very small beyond size 40.
Conclusions: The results of this study suggest that 25 to 30 is the minimum size of the normal database to reliably achieve good performance of semi-quantitative analysis in dopamine transporter (DAT) SPECT, independent of the algorithm used for image reconstruction and the ROI method used to estimate the putaminal SBR
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Multimodal prediction of conversion to Alzheimer's disease based on incomplete biomarkers.
BACKGROUND: This study investigates the prediction of mild cognitive impairment-to-Alzheimer's disease (MCI-to-AD) conversion based on extensive multimodal data with varying degrees of missing values.
METHODS: Based on Alzheimer's Disease Neuroimaging Initiative data from MCI-patients including all available modalities, we predicted the conversion to AD within 3 years. Different ways of replacing missing data in combination with different classification algorithms are compared. The performance was evaluated on features prioritized by experts and automatically selected features.
RESULTS: The conversion to AD could be predicted with a maximal accuracy of 73% using support vector machines and features chosen by experts. Among data modalities, neuropsychological, magnetic resonance imaging, and positron emission tomography data were most informative. The best single feature was the functional activities questionnaire.
CONCLUSION: Extensive multimodal and incomplete data can be adequately handled by a combination of missing data substitution, feature selection, and classification
Characterization of iron-sensitive R2*-qMRI in the Substantia Nigra in Psychotic Spectrum Disorders
Association between DRD2/ANKK1 TaqIA Allele Status and Striatal Dopamine D2/3 Receptor Availability in Alcohol Use Disorder
Background: The association between blunted dopaminergic neurotransmission and alcohol use disorder (AUD) is well-known. In particular, the impairment of postsynaptic dopamine 2 and 3 receptors (DRD2/3) in the ventral and dorsal striatum during the development and maintenance of alcohol addiction has been investigated in several positron emission tomography (PET) studies. However, it is unclear whether these changes are the result of adaptation or genetic predisposition.
Methods: Here we investigated the association between DRD2/ankyrin repeat and kinase domain-containing 1 (ANKK1) TaqIA allele (rs1800497) status and striatal DRD2/3 availability measured by 18F-fallypride PET in 12 AUD patients and 17 sex-matched healthy controls. Age and smoking status were included as covariates.
Results: Contrary to our expectations, TaqIA allele status was not associated with striatal DRD2/3 availability in either group and there was no significant difference between groups, possibly due to the relatively small sample size (N = 29).
Conclusions: Nonetheless, this is the first in vivo study investigating the relationship between dopamine receptor availability and genetic factors in AUD. The pitfalls of assessing such relationships in a relatively small sample are discussed.
Clinical Trial Registration: The published analysis is an additional, post hoc analysis to the preregistered trial with clinical trial number NCT01679145 available on https://clinical - trials.gov/ct2/show/NCT01679145
Effects of spermidine supplementation on cognition and biomarkers in older adults with subjective cognitive decline (SmartAge)—study protocol for a randomized controlled trial
Background: Given the global increase in the aging population and age-related diseases, the promotion of healthy aging is one of the most crucial public health issues. This trial aims to contribute to the establishment of effective approaches to promote cognitive and brain health in older individuals with subjective cognitive decline (SCD). Presence of SCD is known to increase the risk of objective cognitive decline and progression to dementia due to Alzheimer’s disease. Therefore, it is our primary goal to determine whether spermidine supplementation has a positive impact on memory performance in this at-risk group, as compared with placebo. The secondary goal is to examine the effects of spermidine intake on other neuropsychological, behavioral, and physiological parameters.
Methods: The SmartAge trial is a monocentric, randomized, double-blind, placebo-controlled phase IIb trial. The study will investigate 12 months of intervention with spermidine-based nutritional supplementation (target intervention) compared with 12months of placebo intake (control intervention). We plan to recruit 100 cognitively normal older individuals with SCD from memory clinics, neurologists and general practitioners in private practice, and the general population. Participants will be allocated to one of the two study arms using blockwise randomization stratified by age and sex with a 1:1 allocation ratio. The primary outcome is the change in memory performance between baseline and post-intervention visits (12 months after baseline). Secondary outcomes include the change in memory performance from baseline to follow-up assessment (18months after baseline), as well as changes in neurocognitive, behavioral, and physiological parameters (including blood and neuroimaging biomarkers), assessed at baseline and post-intervention.
Discussion: The SmartAge trial aims to provide evidence of the impact of spermidine supplementation on memory performance in older individuals with SCD. In addition, we will identify possible neurophysiological mechanisms of action underlying the anticipated cognitive benefits. Overall, this trial will contribute to the establishment of nutrition intervention in the prevention of Alzheimer’s disease
Considerations on brain age predictions from repeatedly sampled data across time
Introduction
Brain age, the estimation of a person's age from magnetic resonance imaging (MRI) parameters, has been used as a general indicator of health. The marker requires however further validation for application in clinical contexts. Here, we show how brain age predictions perform for the same individual at various time points and validate our findings with age-matched healthy controls.
Methods
We used densely sampled T1-weighted MRI data from four individuals (from two densely sampled datasets) to observe how brain age corresponds to age and is influenced by acquisition and quality parameters. For validation, we used two cross-sectional datasets. Brain age was predicted by a pretrained deep learning model.
Results
We found small within-subject correlations between age and brain age. We also found evidence for the influence of field strength on brain age which replicated in the cross-sectional validation data and inconclusive effects of scan quality.
Conclusion
The absence of maturation effects for the age range in the presented sample, brain age model bias (including training age distribution and field strength), and model error are potential reasons for small relationships between age and brain age in densely sampled longitudinal data. Clinical applications of brain age models should consider of the possibility of apparent biases caused by variation in the data acquisition process.publishedVersio
CT-Based Attenuation Correction in I-123-Ioflupane SPECT
Purpose Attenuation correction (AC) based on low-dose computed tomography (CT)
could be more accurate in brain single-photon emission computed tomography
(SPECT) than the widely used Chang method, and, therefore, has the potential
to improve both semi-quantitative analysis and visual image interpretation.
The present study evaluated CT-based AC for dopamine transporter SPECT with
I-123-ioflupane. Materials and methods Sixty-two consecutive patients in whom
I-123-ioflupane SPECT including low-dose CT had been performed were recruited
retrospectively at 3 centres. For each patient, 3 different SPECT images were
reconstructed: without AC, with Chang AC and with CT-based AC. Distribution
volume ratio (DVR) images were obtained by scaling voxel intensities using the
whole brain without striata as reference. For assessing the impact of AC on
semi-quantitative analysis, specific-to-background ratios (SBR) in caudate and
putamen were obtained by fully automated SPM8-based region of interest (ROI)
analysis and tested for their diagnostic power using receiver-operator-
characteristic (ROC) analysis. For assessing the impact of AC on visual image
reading, screenshots of stereotactically normalized DVR images presented in
randomized order were interpreted independently by two raters at each centre.
Results CT-based AC resulted in intermediate SBRs about half way between no AC
and Chang. Maximum area under the ROC curve was achieved by the putamen SBR,
with negligible impact of AC (0.924, 0.935 and 0.938 for no, CT-based and
Chang AC). Diagnostic accuracy of visual interpretation also did not depend on
AC. Conclusions The impact of CT-based versus Chang AC on the interpretation
of I-123-ioflupane SPECT is negligible. Therefore, CT-based AC cannot be
recommended for routine use in clinical patient care, not least because of the
additional radiation exposure
Dopamine D2/3 receptor availability in alcohol use disorder and individuals at high risk: Towards a dimensional approach
Alcohol use disorder (AUD) is the most common substance use disorder worldwide. Although dopamine-related findings were often observed in AUD, associated neurobiological mechanisms are still poorly understood. Therefore, in the present study, we investigate D2/3 receptor availability in healthy participants, participants at high risk (HR) to develop addiction (not diagnosed with AUD), and AUD patients in a detoxified stage, applying F-18-fallypride positron emission tomography (F-18-PET). Specifically, D2/3 receptor availability was investigated in (1) 19 low-risk (LR) controls, (2) 19 HR participants, and (3) 20 AUD patients after alcohol detoxification. Quality and severity of addiction were assessed with clinical questionnaires and (neuro)psychological tests. PET data were corrected for age of participants and smoking status. In the dorsal striatum, we observed significant reductions of D2/3 receptor availability in AUD patients compared with LR participants. Further, receptor availability in HR participants was observed to be intermediate between LR and AUD groups (linearly decreasing). Still, in direct comparison, no group difference was observed between LR and HR groups or between HR and AUD groups. Further, the score of the Alcohol Dependence Scale (ADS) was inversely correlated with D2/3 receptor availability in the combined sample. Thus, in line with a dimensional approach, striatal D2/3 receptor availability showed a linear decrease from LR participants to HR participants to AUD patients, which was paralleled by clinical measures. Our study shows that a core neurobiological feature in AUD seems to be detectable in an early, subclinical state, allowing more individualized alcohol prevention programs in the future
Quantitative assessment of the asphericity of pretherapeutic FDG uptake as an independent predictor of outcome in NSCLC
Background The aim of the present study was to evaluate the predictive value
of a novel quantitative measure for the spatial heterogeneity of FDG uptake,
the asphericity (ASP) in patients with non-small cell lung cancer (NSCLC).
Methods FDG-PET/CT had been performed in 60 patients (15 women, 45 men; median
age, 65.5 years) with newly diagnosed NSCLC prior to therapy. The FDG-PET
image of the primary tumor was segmented using the ROVER 3D segmentation tool
based on thresholding at the volume-reproducing intensity threshold after
subtraction of local background. ASP was defined as the relative deviation of
the tumor’s shape from a sphere. Univariate and multivariate Cox regression as
well as Kaplan-Meier (KM) analysis and log-rank test with respect to overall
(OAS) and progression-free survival (PFS) were performed for clinical
variables, SUVmax/mean, metabolically active tumor volume (MTV), total lesion
glycolysis (TLG), ASP and “solidity”, another measure of shape irregularity.
Results ASP, solidity and “primary surgical treatment” were significant
independent predictors of PFS in multivariate Cox regression with binarized
parameters (HR, 3.66; p < 0.001, HR, 2.11; p = 0.05 and HR, 2.09; p = 0.05),
ASP and “primary surgical treatment” of OAS (HR, 3.19; p = 0.02 and HR, 3.78;
p = 0.01, respectively). None of the other semi-quantitative PET parameters
showed significant predictive value with respect to OAS or PFS. Kaplan-Meier
analysis revealed a probability of 2-year PFS of 52% in patients with low ASP
compared to 12% in patients with high ASP (p < 0.001). Furthermore, it showed
a higher OAS rate in the case of low versus high ASP (1-year-OAS, 91% vs. 67%:
p = 0.02). Conclusions The novel parameter asphericity of pretherapeutic FDG
uptake seems to provide better prognostic value for PFS and OAS in NCSLC
compared to SUV, metabolic tumor volume, total lesion glycolysis and solidity
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