Only a few Methyl-[11C]-l-methionine (MET) positron emission tomography (PET) studies have focused on children and young adults with brain neoplasm. Due to radiation exposure, long scan acquisition time, and the need for sedation in young children MET-PET studies should be restricted to this group of patients when a decision for further therapy is not possible from routine diagnostic procedures alone, e.g., structural imaging. We investigated the diagnostic accuracy of MET-PET for the differentiation between tumorous and non-tumorous lesions in this group of patients. Forty eight MET-PET scans from 39 patients aged from 2 to 21 years (mean 15 \u00b1 5.0 years) were analyzed. The MET tumor-uptake relative to a corresponding control region was calculated. A receiver operating characteristic (ROC) was performed to determine the MET-uptake value that best distinguishes tumorous from non-tumorous brain lesions. A differentiation between tumorous (n = 39) and non-tumorous brain lesions (n = 9) was possible at a threshold of 1.48 of relative MET-uptake with a sensitivity of 83% and a specificity of 92%, respectively. A differentiation between high grade malignant lesions (mean MET-uptake = 2.00 \u00b1 0.46) and low grade tumors (mean MET-uptake = 1.84 \u00b1 0.31) was not possible. There was a significant difference in MET-uptake between the histologically homogeneous subgroups of astrocytoma WHO grade II and anaplastic astrocytoma WHO grade III (P = 0.02). MET-PET might be a useful tool to differentiate tumorous from non-tumorous lesions in children and young adults when a decision for further therapy is difficult or impossible from routine structural imaging procedures alone.
\n \n\n \n \nBackground:: Inconsistent changes of cognitive functioning have been reported in patients with Parkinson disease (PD) with deep brain stimulation (DBS) of the subthalamic nucleus (STN). To investigate the underlying pathomechanisms, we correlated alterations of cognitive test performance and changes of neuronal energy metabolism in frontal basal ganglia projection areas under bilateral STN stimulation. METHODS:: We conducted verbal fluency, learning, and memory tests and 18-fluorodeoxyglucose (FDG) PET in nine patients with PD with STN-DBS before and 6 months after surgery. Using coregistered MRI, postoperative changes of the normalized cerebral metabolic rates of glucose (nCMRGlc) in the dorsolateral prefrontal cortex (DLPFC), lateral orbitofrontal cortex (LOFC), ventral and dorsal cingulum (v/dACC), and in Broca area were determined and correlated with alterations of neuropsychological test results. RESULTS:: After surgery, highly variable changes of both cognitive test performance and frontal nCMRGlc values were found with significant correlations between verbal fluency and FDG uptake in the left DLPFC (Brodmann area [BA] 9, 46), left Broca area (BA 44/45), and the right dACC (BA 32). A decrease of nCMRGlc in the left OFC (BA 11/47) and dACC (BA 32) correlated with a decline of verbal learning. All patients showed reduced metabolic activity in the right anterior cingulate cortex after DBS. Baseline cognitive abilities did not predict verbal learning or fluency changes after surgery. CONCLUSIONS:: These data show a significant linear relationship between changes in frontal 18-fluorodeoxyglucose PET activity and changes in cognitive outcome after deep brain stimulation of the subthalamic nucleus (STN) in advanced Parkinson disease. The best correlations were found in the left frontal lobe (dorsolateral prefrontal cortex and Broca area). Baseline performance on cognitive tests did not predict cognitive or metabolic changes after STN electrode implantation. \u00a9 2009 AAN Enterprises, Inc.
\n \n\n \n \nA method for fast quantitative T2* mapping based on multiple gradient-echo (multi-GE) imaging with correction for static magnetic field inhomogeneities is described, using an exponential excitation pulse. Field gradient maps are obtained from the phase information and modulus data are subsequently corrected, allowing for simple monoexponential T2* fitting. Echoes with long echo times suffering from major signal losses due to field inhomogeneities are excluded from the analysis. The acquisition time for a matrix size of 256 x 256, 1 mm in-plane resolution, and 2 mm slice thickness amounts to 15 s per slice. An additional correction for in-plane field gradients further improves accuracy. Phantom experiments show that the method provides accurate T2* values for field gradients up to 200 \u03bcT/m; for gradients up to 300 \u03bcT/m errors do not exceed 15%. In vivo T 2* values acquired on healthy volunteers at 3T are in excellent agreement with results from the literature. \u00a9 2009 Wiley-Liss, Inc.
\n \n\n \n \nObjective: Imaging studies of the motor system employing active motor tasks have been applied extensively in patients after ischemic stroke (1-3), but have not yielded reliable measures for predicting recovery. This might be in part due to the complexity and flexibility of the motor system to cope with lesions, in part to the variability of the lesion site causing motoric deficits. Little is known about the role of the proprioceptive system for recovery after stroke despite rehabilitation strategies utilize proprioceptive facilitation (4) and despite the role of proprioceptors for spasticity. This study was designed to investigate the activity of the proprioceptive system during early recovery after pure motor stroke. Methods: Ten patients with unilateral infarction of the posterior limb of the internal capsule were investigated using O-15-water PET during passive extension of the index finger of the paretic and non-paretic hands. PET scanning and assessment of motor recovery were performed early (mean 4.7 days) and after rehabilitation with 30 minutes of physiotherapy daily for an average of 17.6 days. Changes in brain activation patterns induced by passive finger movement were analyzed using SPM99. Results: All patients showed significant improvement of motor-function of the paretic limb after rehabilitation. During passive finger movement of the non-paretic index-finger, significant CBF-increases were observed in the SI (BA3) and SII (BA 40 and 39) areas of the non-infarcted hemisphere, as previously reported for normal subjects. Additionally, significant activation of ipsilateral SII in the infarcted hemisphere was observed. After rehabilitation ipsilateral SII activation vanished and the normal activation pattern was restored. During passive movement of the paretic index-finger opposite changes of activation patterns were observed. Initially only SI and SII of the infarcted hemisphere were activated, like in normal subjects. During rehabilitation additional recruitment of SII in the non-infarcted hemisphere occurred. Conclusion: Recovery from internal capsule infarction is accompanied by substantial changes in activity of proprioceptive systems not only of the paretic but also of the non-paretic limb. These changes are evident in ipsilateral activity of SII during the acute phase of stroke, which vanishes for stimulation of the non-paretic limb after recovery, but newly occurs after rehabilitation of the paretic limb. The consecutive alternating activations of SII are observed during non-complex, non-sequential passive movements. These changes in the activation patterns cannot be easily explained by plasticity of the proprioceptive system, since the time span is too short for adaptation. It might in part be due to a reduction of transcallosal inhibition of the affected onto the intact hemisphere; it may also reflect an interhemispheric shift of attention to proprioceptive stimuli associated with recovery.
\n \n\n \n \nThe corpus callosum (CC) is the principal white matter fiber bundle connecting neocortical areas of the two hemispheres. Although an object of extensive research, important details about the anatomical and functional organization of the human CC are still largely unknown. Here we focused on the callosal motor fibers (CMFs) that connect the primary motor cortices (M1) of the two hemispheres. Topography and somatotopy of CMFs were explored by using a combined functional magnetic resonance imaging/diffusion tensor imaging fiber-tracking procedure. CMF microstructure was assessed by fractional anisotropy (FA), and CMF functional connectivity between the hand areas of M1 was measured by interhemispheric inhibition using paired-pulse transcranial magnetic stimulation. CMFs mapped onto the posterior body and isthmus of the CC, with hand CMFs running significantly more anteriorly and ventrally than foot CMFs. FA of the hand CMFs but not FA of the foot CMFs correlated linearly with interhemispheric inhibition between the M1 hand areas. Findings demonstrate that CMFs connecting defined body representations of M1 map onto a circumscribed region in the CC in a somatotopically organized manner. The significant and topographically specific positive correlation between FA and interhemispheric inhibition strongly suggests that microstructure can be directly linked to functional connectivity. This provides a novel way of exploring human brain function that may allow prediction of functional connectivity from variability of microstructure in healthy individuals, and potentially, abnormality of functional connectivity in neurological or psychiatric patients. Copyright \u00a9 2007 Society for Neuroscience.
\n \n\n \n \nObjective: To investigate the activity of proprioceptive systems during early recovery of motor function after ischaemic stroke in a prospective, longitudinal, functional imaging study. Methods: Ten patients with unilateral infarction of the posterior internal capsule were investigated using oxygen-15-water positron emission tomography during passive extension of the index finger. Patients were assessed initially after stroke (mean 4.7 days) and again after rehabilitation. Changes in brain activation patterns were analysed. Results: All patients showed significant improvement in motor function of the paretic limb. During passive finger movement of the non-paretic index finger, significant increases in cerebral blood flow were observed in the somatosensory areas I and I1 (SI and SII) of the non-infarcted hemisphere. Additionally, significant activation of ipsilateral SII in the infarcted hemisphere was observed. After rehabilitation, ipsilateral SII activation vanished and the normal activation pattern was restored. During passive movement of the paretic index finger only SI and SII of the infarcted hemisphere were activated. During rehabilitation, additional recruitment of SII in the non-infarcted hemisphere occurred. Conclusion: Recovery from internal capsule infarction is accompanied by substantial changes in activity of proprioceptive systems of the paretic and non-paretic limb. These changes may reflect an inter-hemispheric shift of attention to proprioceptive stimuli associated with recovery. \u00a9 2007 Foundation of Rehabilitation Information.
\n \n\n \n \nFatal familial insomnia (FFI) is a hereditary prion disease caused by a mutation in codon 178 of the prion protein gene PRNP on chromosome 20. It is characterized by disturbed night sleep, resulting in daily vigilance perturbations and a variety of other neurological symptoms. We present the case of a 46-year-old woman deteriorating despite immunosuppressive treatment which was initiated suspecting cerebral vasculitis as the cause of her progressive neurological symptoms. The correct diagnosis was established only post mortem. Based on the case presented here, we discuss typical clinical symptoms and imaging findings. In particular, we outline how modern diagnostic methods such as positron emission tomography with [ 15O]H 2O and [ 18F]FDG and single photon emission computed tomography can add valuable information to results from conventionally performed imaging techniques and genetic testing. \u00a9 Springer Medizin Verlag 2006.
\n \n\n \n \nBecause of the high glucose metabolism in normal brain tissue 18F-FDG is not the ideal tracer for the detection of gliomas. Methyl-11C-L-methionine (11C-MET) is better suited for imaging the extent of gliomas, because it is transported specifically into tumors but only insignificantly into normal brain. 3\u2032-Deoxy-3\u2032- 18F-fluorothymidine (18F-FLT) has been introduced as a proliferation marker in a variety of neoplasias and has promising potential for the detection of brain tumors, because its uptake in normal brain is low. Additionally, the longer half-life might permit differentiation between transport and intracellular phosphorylation. Methods: PET of 18F-FLT and 11C-MET was performed on 23 patients (age range, 20-70 y) with historically verified gliomas of different grades. On all patients, conventional MRI was performed, and 16 patients additionally underwent contrast-enhanced imaging. Images were coregistered, and the volumes of abnormality were defined for PET and MRI. Uptake ratios and standardized uptake values (SUVs) of various tumors and regions were assessed by region-of-interest analysis. Kinetic modeling was performed on 14 patients for regional time-activity curves of 18F-FLT from tumorous and normal brain tissue. Results: Sensitivity for the detection of tumors was lower for 18F-FLT than for 11C-MET (78.3% vs. 91.3%), especially for low-grade astrocytomas. Tumor volumes detected by 18F-FLT and 11C-MET were larger than tumor regions displaying gadolinium enhancement (P < 0.01). Uptake ratios of 18F-FLT were higher than uptake ratios of 11C-MET (P < 0.01). Uptake ratios of 18F-FLT were higher in glioblastomas than in astrocytomas (P < 0.01). Absolute radiotracer uptake of 18F-FLT was low and significantly lower than that of 11C-MET (SUV, 1.3 \u00b1 0.7 vs. 3.1 \u00b1 1.0; P < 0.01). Some tumor regions were detected only by either 18F-FLT (7 patients) or 11C-MET (13 patients). Kinetic modeling revealed that 18F-FLT uptake in tumor tissue seems to be predominantly due to elevated transport and net influx. However, a moderate correlation was found between uptake ratio and phosphorylation rate k3 (r = 0.65 and P = 0.01 for grade II-IV gliomas; r = 0.76 and P < 0.01 for grade III-IV tumors). Conclusion: 18F-FLT is a promising tracer for the detection and characterization of primary central nervous system tumors and might help to differentiate between low- and high-grade gliomas. 18F-FLT uptake is mainly due to increased transport, but irreversible incorporation by phosphorylation might also contribute. In some tumors and tumor areas, 18F-FLT uptake is not related to 11C-MET uptake. In view of the high sensitivity and specificity of 11C-MET PET for imaging of gliomas, it cannot be excluded that 18F-FLT PET was false positive in these areas. However, the discrepancies observed for the various imaging modalities (18F-FLT and 11C-MET PET as well as gadolinium-enhanced MRI) yield complementary information on the activity and the extent of gliomas and might improve early evaluation of treatment effects, especially in patients with high-grade gliomas. Further studies are needed, including coregistered histology and kinetic analysis in patients undergoing chemotherapy.
\n \n\n \n \nObjective: To assess neurochemical deficits in patients with Parkinson disease (PD) associated dementia (PDD) in vivo. Methods: The authors performed combined PET with N-[11C]-methyl-4-piperidyl acetate (MP4A) and 18F-fluorodopa (FDOPA) for evaluation of cholinergic and dopaminergic transmitter changes in 17 non-demented patients with PD and 10 patients with PDD. Data were compared to 31 age-matched controls by a combined region-of-interest and voxel-based Statistical Parametric Mapping analysis. Results: The striatal FDOPA uptake was significantly decreased in PD and PDD without differences between the groups. The global cortical MP4A binding was severely reduced in PDD (29.7%, p < 0.001 vs controls) and moderately decreased in PD (10.7%, p < 0.01 vs controls). The PDD group had lower parietal MP4A uptake rates than did patients with PD. Frontal and temporo-parietal cortices showed a significant covariance of striatal FDOPA reduction and decreased MP4A binding in patients with PDD. Conclusions: While non-demented patients with Parkinson disease had a moderate cholinergic dysfunction, subjects with Parkinson disease associated dementia (PDD) presented with a severe cholinergic deficit in various cortical regions. The finding of a closely associated striatal FDOPA and cortical MP4A binding reduction suggests a common disease process leading to a complex transmitter deficiency syndrome in PDD. Copyright \u00a9 2005 by AAN Enterprises, Inc.
\n \n\n \n \nIdentification of small nuclei in the brain by PET has been limited by the spatial resolution of conventional scanners. The new detector technology and advanced signal analysis of a high-resolution research tomograph (HRRT) has improved 3-dimensional spatial resolution to 2.2 mm at sufficient efficiency and permitted the quantification of tracer concentrations in small volumes. Methods: In 9 healthy volunteers, cerebral glucose metabolism was investigated after intravenous injection of 370 MBq of 18F-FDG, and regional cerebral metabolic rates for glucose (rCMRGlc) were determined in various structures of the brain identified on coregistered MR images using stereotactic and topographic anatomic information. Results: rCMRGlc values (in \u03bcmol/100 g/min) were higher in the cerebral cortex (33.5 \u00b1 2.98), the basal ganglia (32.6 \u00b1 3.04 in the nucleus caudatus and 40.2 \u00b1 3.50 in the putamen), the thalamus (36.6 \u00b1 4.72), and the cerebellum (29.8 \u00b1 2.20) and were lower in the cerebral white matter (12.3 \u00b1 1.45) than those reported previously with conventional scanners. This resulted in an increased ratio of cortical values to white-matter values. Various nuclei in the basal frontal lobe (21.4 \u00b1 3.19 in the basal forebrain and 32.3 \u00b1 2.39 in the nucleus accumbens), the temporal lobe (22.2 \u00b1 1.74 in the corpus amygdalae), the hippocampus (25.7 \u00b1 2.11), the diencephalon (23.1 \u00b1 3.33 in the corpus geniculatum laterale, 20.2 \u00b1 2.87 in the corpus geniculatum mediale, and 25.2 \u00b1 3.29 in the nucleus subthalamicus), and the brain stem (24.4 \u00b1 2.47 in the colliculus superior, 31.4 \u00b1 3.63 in the colliculus inferior, 31.0 \u00b1 3.10 in the nucleus ruber, and 22.8 \u00b1 2.35 in the substantia nigra) could be identified, and the metabolic rate was assessed in these structures. The effect of improved spatial resolution on quantified metabolic rates could directly be demonstrated in a few cases investigated on scanners of different generations. Conclusion: The improved spatial resolution of the HRRT decreased partial-volume effects in the quantification of metabolic rates in the brain and increased the accuracy of rCMRGlc values in large structures. For the first time, this scanner has permitted the determination of metabolic rates in small nuclei that are involved in various neurodegenerative disorders.
\n \n\n \n \nPurpose: Methyl-[11C]L-methionine ([11C]MET) positron emission tomography (PET) in brain tumors reflects amino acid transport and has been shown to be more sensitive than magnetic resonance imaging in stereotactic biopsy planning. It remains unclear whether the increased [11C]MET uptake is limited to solid tumor tissue or even detects infiltrating tumor parts. Experimental Design: In 30 patients, a primary or recurrent brain tumor was suspected on magnetic resonance imaging. Patients were investigated with [11C]MET-PET before stereotactic biopsy. The biopsy trajectories were plotted into the [11C]MET-PET images with a newly designed C-based software program. The exact local [11C]MET uptake was determined within rectangular regions of interest of 4 mm in width and length aligned with the biopsy specimen. Individual histologic specimens were rated for the presence of solid tumor tissue, infiltration area, and nontumorous tissue changes. Results: Receiver operating characteristics analysis demonstrated a sensitivity of 87% and specificity of 89% for the detection of tumor tissue at a threshold of 1.3-fold [11C]MET uptake relative to normal brain tissue. At this threshold, only 13 of 100 tumor positive specimen were false negative mainly in grade 2 astrocytoma. In grade 2 astrocytoma, mean [11C]MET uptake in the infiltration area was significantly higher than in solid tumor tissue (P < 0.003). Conclusions: [11C]MET-PET detects solid parts of brain tumors, as well as the infiltration area at high sensitivity and specificity. High [11C]MET uptake in infiltrating tumor of astrocytoma WHO grade 2 reflects high activity in this tumor compartment. Molecular imaging, with [11C]MET, will guide improved management of patients with brain tumors.
\n \n\n \n \nIn recent years, mutual information has proved to be an excellent criterion for registration of intra-individual images from different modalities. Multi-resolution coarse-to-fine optimization was proposed for speeding-up of the registration process. The aim of our work was to further improve registration speed without compromising robustness or accuracy. We present and evaluate two procedures for co-registration of positron emission tomography (PET) and magnetic resonance (MR) images of human brain that combine a multi-resolution approach with an automatic segmentation of input image volumes into areas of interest and background. We show that an acceleration factor of 10 can be achieved for clinical data and that a suitable preprocessing can improve robustness of registration. Emphasis was laid on creation of an automatic registration system that could be used routinely in a clinical environment. For this purpose, an easy-to-use graphical user interface has been developed. It allows physicians with no special knowledge of the registration algorithm to perform a fast and reliable alignment of images. Registration progress is presented on the fly on a fusion of images and enables visual checking during a registration. \u00a9 2004 Elsevier Inc. All rights reserved.
\n \n\n \n \nWe considered clinical observations in patients with obsessive-compulsive- and anxiety-disorders, who underwent bilateral anterior capsulotomy, as well as anatomical and pathophysiological findings. Based on these considerations, we choose the shell region of the right nucleus accumbens as target for deep brain stimulation (DBS) in a pilot-series of four patients with severe obsessive-compulsive- and anxiety-disorders. Significant reduction in severity of symptoms has been achieved in three of four patients treated. Clinical results as well as a 15-O-H2O-PET study, perfomed in one patient during stimulation, speak in favour of the following hypothesis. As a central relay-structure between amygdala, basal ganglia, mesolimbic dopaminergic areas, mediodorsal thalamus and prefrontal cortex, the accumbens nucleus seems to play a modulatory role in information flow from the amygdaloid complex to the latter areas. If disturbed, imbalanced information flow from the amygdaloid complex could yield obsessive-compulsive- and anxiety-disorders, which can be counteracted by blocking the information flow within the shell region of the accumbens nucleus by deep brain stimulation. \u00a9 2003 Published by Elsevier B.V.
\n \n\n \n \nTo establish the influence of prolonged denervation on the recovery of a motor nerve, the rat facial nerve was transected and denervated for 0 to 224 days. Then, the freshly transected hypoglossal nerve was sutured to the predegenerated facial nerve (hypoglossal-facial nerve anastomosis, HFA). Using this nerve cross-anastomosis paradigm we analyzed the nerve regeneration and muscle reinnervation 7 to 112 days post-suture operation (DPSO). After HRP injection into the whiskerpad 931 \u00b1 27 hypoglossal neurons were labeled at 112 DPSO after immediate HFA. Following 14 to 112 days denervation the number of labeled neurons increased to 138% (14 days delay), 154% (56 days), and 145% (112 days). In contrast, the reinnervation was poorer after 7 days denervation with the number of neurons increasing to 84%, and after long-term denervation of 224 days the number of neurons increased to 81%. The increase in amplitude of evoked electromyography wave after nerve suture correlated with the number of labeled neurons. After immediate HFA each regenerated motoneuron established on average 5.1 myelinated sprouts at 112 DPSO. The number of sprouts remained constant after delayed suture of 14 to 112 days, whereas the slower reinnervation after 7 or 224 days delay was accompanied by a massive sprouting of 9.1 or 8.1, respectively, sprouts per neuron. The muscles showed recovery after any denervation time. The muscle cross-sectional area continuously decreased with longer denervation time. This decrease was only significant after 224 days denervation (67% of the normal value). We conclude that motor nerve reconstruction achieves better functional results after a definite period of denervation when using a nerve cross-anastomosis paradigm. (C) 2000 Academic Press.
\n \n\n \n \nDuring mouse gastrulation, extraembryonic mesoderm (ExEM) contributes to the extraembryonic yolk sac (YS) and allantois, both of which are essential for successful gestation. Although the genetic networks coordinating intra-embryonic mesodermal subtype specification are well studied, ExEM diversification remains poorly understood. Here, we identify that embryoid body (EB) in vitro differentiation generates distinct lineages of mesodermal cells, matching YS and allantois development. Combining in vitro and in vivo mouse models, we discover that Eomesodermin (Eomes) controls the formation of YS-fated ExEM but is dispensable for allantois formation. Furthermore, simultaneous disruption of Eomes and T impedes the specification of any YS or allantois mesoderm, indicating compensatory roles for T during allantois formation upon Eomes depletion. Our study highlights previously unrecognized functional and mechanistic diversity in ExEM diversification and endothelial development and introduces a tractable EB model to dissect the signaling pathways and transcriptional networks driving the formation of key extraembryonic tissues.
\n \n\n \n \nA key aim in epidemiological neuroscience is identification of markers to assess brain health and monitor therapeutic interventions. Quantitative susceptibility mapping (QSM) is an emerging magnetic resonance imaging technique that measures tissue magnetic susceptibility and has been shown to detect pathological changes in tissue iron, myelin and calcification. We present an open resource of QSM-based imaging measures of multiple brain structures in 35,273 individuals from the UK Biobank prospective epidemiological study. We identify statistically significant associations of 251 phenotypes with magnetic susceptibility that include body iron, disease, diet and alcohol consumption. Genome-wide associations relate magnetic susceptibility to 76 replicating clusters of genetic variants with biological functions involving iron, calcium, myelin and extracellular matrix. These patterns of associations include relationships that are unique to QSM, in particular being complementary to T2* signal decay time measures. These new imaging phenotypes are being integrated into the core UK Biobank measures provided to researchers worldwide, creating the potential to discover new, non-invasive markers of brain health.
\n \n\n \n \nOBJECTIVES: Rapid eye movement sleep behavior disorder (RBD) patients have a high risk of developing a Parkinsonian disorder, offering an opportunity for neuroprotective intervention. Predicting near-term conversion, however, remains a challenge. Dopamine transporter imaging, while informative, is expensive and not widely available. Here, we investigate the utility of susceptibility-weighted MRI (SWI) to detect abnormalities of the substantia nigra in RBD, and explore their association with striatal dopaminergic deficits. METHODS: SWI of the substantia nigra was performed in 46 RBD patients, 27 Parkinson's patients, and 32 control subjects. Dorsal nigral hyperintensity (DNH) was scored by two blinded raters, and separately quantified using a semiautomated process. Forty-two RBD patients were also imaged with 123 I-ioflupane single-photon emission computed tomography (DaT SPECT/CT). RESULTS: Consensus visual DNH classification was possible in 87% of participants. 27.5% of RBD patients had lost DNH, compared with 7.7% of control subjects and 96% of Parkinson's patients. RBD patients lacking DNH had significantly lower putamen dopaminergic SPECT/CT activity compared to RBD patients with DNH present (specific uptake ratios 1.89 vs. 2.33, P\u00a0=\u00a00.002). The mean quantified DNH signal intensity declined in a stepwise pattern, with RBD patients having lower intensity than controls (0.837 vs. 0.877, P\u00a0=\u00a00.01) but higher than PD patients (0.837 vs. 0.765, P\u00a0
\n \n\n \n \nOBJECTIVE: We sought to identify motor features that would allow the delineation of individuals with sleep study-confirmed idiopathic REM sleep behavior disorder (iRBD) from controls and Parkinson disease (PD) using a customized smartphone application. METHODS: A total of 334 PD, 104 iRBD, and 84 control participants performed 7 tasks to evaluate voice, balance, gait, finger tapping, reaction time, rest tremor, and postural tremor. Smartphone recordings were collected both in clinic and at home under noncontrolled conditions over several days. All participants underwent detailed parallel in-clinic assessments. Using only the smartphone sensor recordings, we sought to (1) discriminate whether the participant had iRBD or PD and (2) identify which of the above 7 motor tasks were most salient in distinguishing groups. RESULTS: Statistically significant differences based on these 7 tasks were observed between the 3 groups. For the 3 pairwise discriminatory comparisons, (1) controls vs iRBD, (2) controls vs PD, and (3) iRBD vs PD, the mean sensitivity and specificity values ranged from 84.6% to 91.9%. Postural tremor, rest tremor, and voice were the most discriminatory tasks overall, whereas the reaction time was least discriminatory. CONCLUSIONS: Prodromal forms of PD include the sleep disorder iRBD, where subtle motor impairment can be detected using clinician-based rating scales (e.g., Unified Parkinson's Disease Rating Scale), which may lack the sensitivity to detect and track granular change. Consumer grade smartphones can be used to accurately separate not only iRBD from controls but also iRBD from PD participants, providing a growing consensus for the utility of digital biomarkers in early and prodromal PD.
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