Presynaptic Dopaminergic Imaging Characterizes Patients with REM Sleep Behavior Disorder Due to Synucleinopathy.

OBJECTIVE: To apply a machine learning analysis to clinical and presynaptic dopaminergic imaging data of patients with rapid eye movement (REM) sleep behavior disorder (RBD) to predict the development of Parkinson disease (PD) and dementia with Lewy bodies (DLB). METHODS: In this multicenter study of the International RBD study group, 173 patients (mean age 70.5 ± 6.3 years, 70.5% males) with polysomnography-confirmed RBD who eventually phenoconverted to overt alpha-synucleinopathy (RBD due to synucleinopathy) were enrolled, and underwent baseline presynaptic dopaminergic imaging and clinical assessment, including motor, cognitive, olfaction, and constipation evaluation. For comparison, 232 RBD non-phenoconvertor patients (67.6 ± 7.1 years, 78.4% males) and 160 controls (68.2 ± 7.2 years, 53.1% males) were enrolled. Imaging and clinical features were analyzed by machine learning to determine predictors of phenoconversion. RESULTS: Machine learning analysis showed that clinical data alone poorly predicted phenoconversion. Presynaptic dopaminergic imaging significantly improved the prediction, especially in combination with clinical data, with 77% sensitivity and 85% specificity in differentiating RBD due to synucleinopathy from non phenoconverted RBD patients, and 85% sensitivity and 86% specificity in discriminating PD-converters from DLB-converters. Quantification of presynaptic dopaminergic imaging showed that an empirical z-score cutoff of -1.0 at the most affected hemisphere putamen characterized RBD due to synucleinopathy patients, while a cutoff of -1.0 at the most affected hemisphere putamen/caudate ratio characterized PD-converters. INTERPRETATION: Clinical data alone poorly predicted phenoconversion in RBD due to synucleinopathy patients. Conversely, presynaptic dopaminergic imaging allows a good prediction of forthcoming phenoconversion diagnosis. This finding may be used in designing future disease-modifying trials. ANN NEUROL 2024;95:1178-1192.

Whole brain pattern of iron accumulation in REM sleep behavior disorder.

Isolated REM sleep behavior disorder (iRBD) is an early stage of synucleinopathy with most patients progressing to Parkinson's disease (PD) or related conditions. Quantitative susceptibility mapping (QSM) in PD has identified pathological iron accumulation in the substantia nigra (SN) and variably also in basal ganglia and cortex. Analyzing whole-brain QSM across iRBD, PD, and healthy controls (HC) may help to ascertain the extent of neurodegeneration in prodromal synucleinopathy. 70 de novo PD patients, 70 iRBD patients, and 60 HCs underwent 3 T MRI. T1 and susceptibility-weighted images were acquired and processed to space standardized QSM. Voxel-based analyses of grey matter magnetic susceptibility differences comparing all groups were performed on the whole brain and upper brainstem levels with the statistical threshold set at family-wise error-corrected p-values <.05. Whole-brain analysis showed increased susceptibility in the bilateral fronto-parietal cortex of iRBD patients compared to both PD and HC. This was not associated with cortical thinning according to the cortical thickness analysis. Compared to iRBD, PD patients had increased susceptibility in the left amygdala and hippocampal region. Upper brainstem analysis revealed increased susceptibility within the bilateral SN for both PD and iRBD compared to HC; changes were located predominantly in nigrosome 1 in the former and nigrosome 2 in the latter group. In the iRBD group, abnormal dopamine transporter SPECT was associated with increased susceptibility in nigrosome 1. iRBD patients display greater fronto-parietal cortex involvement than incidental early-stage PD cohort indicating more widespread subclinical neuropathology. Dopaminergic degeneration in the substantia nigra is paralleled by susceptibility increase, mainly in nigrosome 1.

Increased Transferrin Sialylation Predicts Phenoconversion in Isolated REM Sleep Behavior Disorder.

BACKGROUND: Sialic acid-protein interactions are involved in regulating central nervous system immunity; therefore, derangements in sialylation could be involved in neurodegeneration. OBJECTIVES: We evaluate the differences in serum transferrin sialylation in prodromal and early-stage Parkinson's disease (PD), its relation to substantia nigra degeneration, and the risk of phenoconversion to manifest disease. METHODS: Sixty treatment-naive PD patients; 72 polysomnography-confirmed isolated rapid eye movement sleep behavior disorder (iRBD) patients, that is, patients with prodromal synucleinopathy; and 46 healthy volunteers aged ≥45 years and drinking ≤60 standard drinks per month were included. The proportion of serum low-sialylated, carbohydrate-deficient transferrin (CDT) isoforms was assessed using high-performance liquid chromatography, and the values were adjusted for alcohol intake (CDTadj ). Dopamine transporter single-photon emission computed tomography (DaT-SPECT) imaging was performed. In iRBD, phenoconversion risk of DaT-SPECT and CDTadj was evaluated using Cox regression adjusted for age and sex. RESULTS: Median CDTadj was lower in PD (1.1 [interquartile range: 1.0-1.3]%) compared to controls (1.2 [1.1-1.6]%) (P = 0.001). In iRBD, median CDTadj was lower in subjects with abnormal (1.1 [0.9-1.3]%) than normal (1.3 [1.2-1.6]%) DaT-SPECT (P = 0.005). After a median 44-month follow-up, 20% of iRBD patients progressed to a manifest disease. Although iRBD converters and nonconverters did not significantly differ in CDTadj levels (P = 0.189), low CDTadj increased the risk of phenoconversion with hazard ratio 3.2 (P = 0.045) but did not refine the phenoconversion risk associated with abnormal DaT-SPECT yielding hazard ratio 15.8 (P < 0.001). CONCLUSIONS: Decreased serum CDTadj is associated with substantia nigra degeneration in synucleinopathies. iRBD patients with low CDTadj are more likely to phenoconvert to manifest disease. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson Movement Disorder Society.

Dopaminergic imaging and clinical predictors for phenoconversion of REM sleep behaviour disorder.

This is an international multicentre study aimed at evaluating the combined value of dopaminergic neuroimaging and clinical features in predicting future phenoconversion of idiopathic REM sleep behaviour (iRBD) subjects to overt synucleinopathy. Nine centres sent 123I-FP-CIT-SPECT data of 344 iRBD patients and 256 controls for centralized analysis. 123I-FP-CIT-SPECT images were semiquantified using DaTQUANTTM, obtaining putamen and caudate specific to non-displaceable binding ratios (SBRs). The following clinical variables were also analysed: (i) Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale, motor section score; (ii) Mini-Mental State Examination score; (iii) constipation; and (iv) hyposmia. Kaplan-Meier survival analysis was performed to estimate conversion risk. Hazard ratios for each variable were calculated with Cox regression. A generalized logistic regression model was applied to identify the best combination of risk factors. Bayesian classifier was used to identify the baseline features predicting phenoconversion to parkinsonism or dementia. After quality check of the data, 263 iRBD patients (67.6 ± 7.3 years, 229 males) and 243 control subjects (67.2 ± 10.1 years, 110 males) were analysed. Fifty-two (20%) patients developed a synucleinopathy after average follow-up of 2 years. The best combination of risk factors was putamen dopaminergic dysfunction of the most affected hemisphere on imaging, defined as the lower value between either putamina (P < 0.000001), constipation, (P < 0.000001) and age over 70 years (P = 0.0002). Combined features obtained from the generalized logistic regression achieved a hazard ratio of 5.71 (95% confidence interval 2.85-11.43). Bayesian classifier suggested that patients with higher Mini-Mental State Examination score and lower caudate SBR asymmetry were more likely to develop parkinsonism, while patients with the opposite pattern were more likely to develop dementia. This study shows that iRBD patients older than 70 with constipation and reduced nigro-putaminal dopaminergic function are at high risk of short-term phenoconversion to an overt synucleinopathy, providing an effective stratification approach for future neuroprotective trials. Moreover, we provide cut-off values for the significant predictors of phenoconversion to be used in single subjects.

Assessment of renal function before contrast media injection: right decisions based on inaccurate estimates.

OBJECTIVES: Information on renal function required before specified radiological examinations with contrast agents is usually obtained through prediction equations using serum creatinine and anthropometric data. The aim of our study was to demonstrate discrepancy between poor prediction and good diagnostic accuracy of glomerular filtration rate (GFR) estimated by prediction equations. METHODS: In 50 patients, reference GFR was measured as plasma clearance of 51-chromium labeled ethylene-diamine-tetraacetic-acid (51Cr-EDTA) and compared with GFR assayed by creatinine clearance (CC) and estimated by Cockcroft-Gault prediction equation (CG). For comparisons, CC and CG were considered as continuous, categorical, and binary variables. Accuracy of the reference GFR prediction was expressed in terms of prediction errors and diagnostic accuracy indices. RESULTS: As continuous variable, CG estimated individual values of GFR with large prediction error exceeding that of CC. As categorical variable, it classified the patient stage of chronic kidney disease (CKD) with medium diagnostic accuracy of 74% (CKD 3) and 62% (CKD 4). As binary variable, CG classified individual patient's GFR below 30 and 60 ml/min/1.73 m2 with good diagnostic accuracy of 80 and 94%, respectively. Performance of other prediction equations did not significantly differ from CG. CONCLUSIONS: Despite large variance and poor prediction accuracy of individual GFR estimates, most of them correctly classified individual patient's GFR below specified level. Results of prediction equations thus should be used and reported exclusively as binary variables, while numerical values of GFR, if required, should be measured by more accurate radionuclide or laboratory methods. KEY POINTS: • Radiological guidelines on contrast media require estimation of glomerular filtration rate to assess kidney function before specified contrast examinations. • Estimated glomerular filtration rate is obtained through prediction equations using serum creatinine and anthropometric data as predictors. • While numerical estimates of glomerular filtration rate are inaccurate (their prediction accuracy is poor), diagnostic accuracy of binary estimates (ability to classify patient's glomerular filtration rate below or above a specified level) is very good.

SISCOM and FDG-PET in patients with non-lesional extratemporal epilepsy: correlation with intracranial EEG, histology, and seizure outcome.

AIMS: To assess the practical localising value of subtraction ictal single-photon emission computed tomography (SISCOM) coregistered with MRI and (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) in patients with extratemporal epilepsy and normal MRI. METHODS: We retrospectively studied a group of 14 patients who received surgery due to intractable epilepsy and who were shown to have focal cortical dysplasia, undetected by MRI, based on histological investigation. We coregistered preoperative SISCOM and PET images with postoperative MRI and visually determined whether the SISCOM focus, PET hypometabolic area, and cerebral cortex, exhibiting prominent abnormalities on intracranial EEG, were removed completely, incompletely, or not at all. These results and histopathological findings were compared with postoperative seizure outcome. RESULTS: Two patients underwent one-stage multimodal image-guided surgery and the remaining 12 underwent long-term invasive EEG. SISCOM findings were localised for all but 1 patient. FDG-PET was normal in 3 subjects, 2 of whom had favourable postsurgical outcome (Engel class I and II). Complete resection of the SISCOM focus (n=3), the area of PET hypometabolism (n=2), or the cortical regions with intracranial EEG abnormalities (n=7) were predictive of favourable postsurgical outcome. Favourable outcome was also encountered in: 4 of 8 patients with incomplete resection and 1 of 2 with no resection of the SISCOM focus; 4 of 7 patients with incomplete resection and 1 of 2 with no resection of the PET hypometabolic area; and 2 of 7 patients with incomplete resection of the area corresponding to intracranial EEG abnormality. No correlation between histopathological FCD subtype and seizure outcome was observed. CONCLUSION: Complete resection of the dysplastic cortex localised by SISCOM, FDG-PET or intracranial EEG is a reliable predictor of favourable postoperative seizure outcome in patients with non-lesional extratemporal epilepsy.

How the 99mTc-DMSA scintigraphy findings are reflected in the adopted treatment of primary vesicoureteral reflux: One centre experience.

BACKGROUND: Renal changes may have long-term sequalae and prevention is a main goal of management of primary vesicoureteral reflux (VUR). AIM: This study aims to reveal how much 99mTc-DMSA scintigraphy findings are reflected in the adopted surgical or non-surgical treatment in children with diagnosed primary VUR and to give the clinicians information regarding their final therapeutic decision. PATIENTS AND METHODS: A total 207 children with primary VUR who underwent non-acute 99mTc-DMSA scan were retrospectively evaluated. The presence of renal changes, their grading, differential function asymmetry (<45%) and grade of VUR were compared with subsequent choice of therapy. RESULTS: Altogether 92 (44%) children had asymmetric differential function, 122 (59%) showed presence of renal changes, 79 (38%) had high-grade VUR (IV-V). Patients with renal changes had lower differential function (41%vs.48%) and higher grade of VUR. The incidence of high-grade changes (G3+G4B) afflicting more than one third of the kidney was significantly different between grade I-II, III and IV-V VUR (9%, 27%, 48%, respectively). Renal changes were detected in 76% of surgically and 48% of non-surgically treated patients, high-grade 99mTc-DMSA changes in 69% and 31%, respectively. In children with no scars/dysplasia (G0+G4A), non-surgical treatment prevailed in 77%. The independent predictors for surgical intervention were presence of renal changes and higher grade of VUR, but not functional asymmetry. DISCUSSION: Over the last 20 years, there has been a shift toward more non-surgical management of VUR. The long-term outcome of this approach should be thoroughly studied. This is the first study analysing renal status in VUR patients using 99mTc-DMSA scan and its grading regarding the adopted treatment. Renal changes in almost half of non-surgically treated children with VUR should be an indicator for earlier diagnosis and effective treatment of acute pyelonephritis and VUR. We recommend distinguishing grade III VUR, as a moderate-grade VUR, because it is linked to higher incidence of high-grade 99mTc-DMSA changes (G3+G4B); our findings of 65% of grade III VURs treated non-surgically should be cautionary. Grade III VUR does not mean a low-risk condition and should alert the clinician to evaluate the extent of renal changes and unmask high-risk cases. CONCLUSIONS: Our data strengthens the need to investigate the extent of renal changes in VUR patients regarding treatment decision. Performing 99mTc-DMSA scan individualizes the treatment of VUR patients; its grading can distinguish grade III-VUR as a separate risk entity because it differs significantly in terms of incidence of high-grade renal changes and chosen therapy.

Serum but not cerebrospinal fluid levels of allantoin are increased in de novo Parkinson's disease.

Oxidative stress supposedly plays a role in the pathogenesis of Parkinson's disease (PD). Uric acid (UA), a powerful antioxidant, is lowered in PD while allantoin, the oxidation product of UA and known biomarker of oxidative stress, was not systematically studied in PD. We aim to compare serum and cerebrospinal fluid (CSF) levels of UA, allantoin, and allantoin/UA ratio in de novo PD patients and controls, and evaluate their associations with clinical severity and the degree of substantia nigra degeneration in PD. We measured serum and CSF levels of UA, allantoin, and allantoin/UA ratio in 86 PD patients (33 females, mean age 57.9 (SD 12.6) years; CSF levels were assessed in 51 patients) and in 40 controls (19 females, 56.7 (14.1) years). PD patients were examined using Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS), Montreal Cognitive Assessment (MoCA), Scales for Outcomes in Parkinson Disease-Autonomic (SCOPA-AUT), the University of Pennsylvania Smell Identification Test (UPSIT), one-night video-polysomnography, and dopamine transporter single-photon emission computed tomography (DAT-SPECT). Serum allantoin and allantoin/UA ratio were significantly increased in the PD group compared to controls (p < 0.001 and p = 0.002, respectively). Allantoin/UA ratios in serum and CSF were positively associated with the SCOPA-AUT score (p = 0.005 and 0.031, respectively) and RBD presence (p = 0.044 and 0.028, respectively). In conclusion, serum allantoin and allantoin/UA ratio are elevated in patients with de novo PD. Allantoin/UA ratio in serum and CSF is associated with autonomic dysfunction and RBD presence, indicating that higher systemic oxidative stress occurs in PD patients with more diffuse neurodegenerative changes.

Patients with REM sleep behavior disorder have higher serum levels of allantoin.

INTRODUCTION: Rapid eye movement (REM) sleep behavior disorder (RBD) is associated with an increased risk of developing Parkinson's disease (PD). Low uric acid (UA) levels are associated with the risk of development and progression of PD. Allantoin is the major oxidation product of UA and is considered as a biomarker of oxidative stress. We aimed to compare serum levels of UA, allantoin, and allantoin/UA ratio in RBD patients with those in healthy controls, and to examine their associations with clinical severity. METHODS: We evaluated serum levels of UA, allantoin, and allantoin/UA ratio in 38 RBD patients (one female, mean age 66.8 (SD 6.3) years) and in 47 controls (four females, 66.8 (7.6) years). All RBD patients were assessed according to an examination protocol, which included structured interview, Montreal Cognitive Assessment (MoCA), Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS), and dopamine transporter single-photon emission computed tomography (DAT-SPECT). The lower putaminal binding ratio from both hemispheres was used for analysis. RESULTS: Mean serum allantoin concentration and allantoin/UA ratio were significantly increased in the RBD group compared to controls (2.6 (1.8) vs. 1.4 (0.7) µmol/l, p = 0.0004, and 0.008 (0.004) vs. 0.004 (0.002), p < 0.0001, respectively). There were no significant differences in UA levels between the two groups. No significant associations between any biochemical parameter and RBD duration, putaminal binding ratio on DAT-SPECT, MDS-UPDRS, or MoCA score were found. CONCLUSION: Serum allantoin and allantoin/UA ratio are increased in RBD patients in comparison to controls, which may reflect increased systemic oxidative stress in prodromal synucleinopathy.

Systematic video-analysis of motor events during REM sleep in idiopathic REM sleep behavior disorder, follow-up and DAT-SPECT.

Abnormal motor manifestations in REM sleep are the most visible feature of idiopathic REM sleep behavior disorder (iRBD), which precedes the overt alpha-synucleinopathy. The aim of this study was to perform a systematic visual analysis of the motor events (ME) captured during video-polysomnography, and clarify their relation to the disease severity. Thirty-four iRBD patients (5 women, 29 men; age 67.7 ± 7.2) with a mean follow-up duration 2.9 ± 1.1 years. and 33 controls (10 women, 23 men; age 61.5 ± 8.2) were examined. The ME captured during REM sleep were classified into four categories, previously defined by Frauscher et al. according to clinical severity: minor/simple jerks, major, complex and violent. An average frequency of 110.8 ± 75.2 ME per hour were identified in iRBD, 7.5 ± 11.6 in the controls (p < 0.001). Of these ME, 68.4% were classified as minor/simple jerks, 9.3% as major, 21.7% as complex and 0.7% as violent. The ME frequency was negatively associated with tracer binding on dopamine transporter single-photon emission computed tomography (DAT-SPECT); the association was stronger for caudate nucleus compared to putamen. During follow-up seven patients (24.1%) phenoconverted, yielding a yearly phenoconversion rate 8.3%. Violent ME were associated with increased hazard ratio for phenoconversion in frequency (p = 0.012) and total duration (p = 0.007). Patients with higher amounts of violent ME had a greater risk of phenoconversion; therefore, their role as a predictor should be considered. Additionally, ME were associated with nigrostriatal degeneration, according to DAT-SPECT. These findings indicate that the degree of the clinical severity of motor manifestations in iRBD reflects the severity of the disease.

Efficiency of 123I-ioflupane SPECT as the marker of basal ganglia damage in acute methanol poisoning: 6-year prospective study.

CONTEXT: Investigate whether 123I-ioflupane SPECT (DaT SPECT) has the potential as a marker of basal ganglia damage in acute methanol poisoning. METHODS: Prospective, single-centre, cohort study of patients with confirmed methanol poisoning was conducted. DaT SPECT was performed twice with semi-quantification using DaTQUANTTM and MRI-based volumetry was calculated. Specific binding ratios (SBR) of striatum, caudate nucleus, and putamen were correlated with laboratory parameters of outcome, volumetric data, and retinal nerve fibres layer (RNFL) thickness measurements. RESULTS: Forty-two patients (mean age 46.3 ± 4.2 years; 8 females), including 15 with MRI-detected putamen lesions (group I) and 27 patients with intact putamen (group II), underwent DaT SPECT. Volumetry was calculated in 35 of the patients assessed. SBR values for the left putamen correlated with putamen volume (r = 0.665; p < 0.001). Decreased bilateral SBR values were determined for the striatum and the putamen, but not for the nucleus caudate, in group I (p < 0.05). Significant correlation was observed between the SBR of the posterior putamen and arterial blood pH (r = 0.574; p < 0.001) and other toxicological parameters of severity of poisoning/outcome including serum lactate, glucose, and creatinine concentrations (p < 0.05). The SBR of the posterior putamen positively correlated with the global RNFL thickness (p < 0.05). ROC analysis demonstrated a significant discriminatory ability of SBR of the posterior putamen with AUC = 0.753 (95%CI 0.604-0.902; p = 0.007). The multivariate regression model demonstrated that arterial blood pH, age, and gender were the most significant factors associated with SBR of the posterior putamen. CONCLUSION: DaT SPECT demonstrates significant potential for the diagnosis of methanol-induced basal ganglia damage.

MRI-guided voxel-based automatic semi-quantification of dopamine transporter imaging.

PURPOSE: Functional imaging with 123I-FP-CIT SPECT suffers from poor spatial resolution resulting in partial-volume effect, which affects the subsequent semi-quantification. Definition of regions of interest for semi-quantification is further subject to user's experience and inter-observer variability. The aim of this work has been to develop an automatic method for definition of volumes of interest and partial-volume correction using patient-specific MRI and providing complete contrast recovery in striatal region. METHOD: The method consists of spatial pre-processing (image segmentation and multi-modality registration), partial-volume correction (performed by region-based voxel-wise technique), and calculation of uptake indices in striatal structures. Anthropomorphic striatal phantom was used to optimize the method and to assess linearity, accuracy, and reproducibility. The method was tested on 58 patient datasets and compared with clinical assessment and BasGan software. RESULTS: The method works automatically. The output is highly linear regarding changing striatal uptake. Complete contrast recovery is achieved using 6.5 mm FWHM. Accuracy is better than 0.15 in terms of RMSE between measured and true uptake indices. Reproducibility is better than 5% for normal uptake ratio. The method outperformed clinical assessment in all measures. With patient data, it provided results closer to BasGan (RMSE 0.9) than to clinical assessment (RMSE 1.9) and fairly correlated with both. CONCLUSION: The proposed method provides complete recovery of striatal contrast under given acquisition and reconstruction conditions. It reduces intra- and inter-observer variability, accurately defines volumes of interest, and effectively suppresses partial-volume effect. It can be reproduced using publicly available software.

Operationalising resilience for disaster medicine practitioners: capability development through training, simulation and reflection.

Resilience has in recent decades been introduced as a term describing a new perspective within the domains of disaster management and safety management. Several theoretical interpretations and definitions of the essence of resilience have been proposed, but less work has described how to operationalise resilience and implement the concept within organisations. This case study describes the implementation of a set of general resilience management guidelines for critical infrastructure within a Swedish Regional Medical Command and Control Team. The case study demonstrates how domain-independent guidelines can be contextualised and introduced at an operational level, through a comprehensive capability development programme. It also demonstrates how a set of conceptual and reflective tools consisting of educational, training and exercise sessions of increasing complexity and realism can be used to move from high-level guidelines to practice. The experience from the case study demonstrates the value of combining (1) developmental learning of practitioners' cognitive skills through resilience-oriented reflection and interaction with dynamic complex open-ended problems; (2) contextualisation of generic guidelines as a basis for operational methodological support in the operational environment; and (3) the use of simulation-based training as part of a capability development programme with increasing complexity and realism across mixed educational, training and exercise sessions. As an actual example of a resilience implementation effort in a disaster medicine management organisation, the study contributes to the body of knowledge regarding how to implement the concept of resilience in operational practice.

Scintigraphy with 99mTc-HMPAO labeled leukocytes is still an accurate and convenient tool to rule out suspected inflammatory bowel disease in children.

BACKGROUND: Abdominal pain is a common complaint in children and its differential diagnosis includes inflammatory bowel disease (IBD). The aim of the study was to assess the diagnostic accuracy of scintigraphy with 99mTechnetium Hexamethylpropyleneamine Oxime (99mTc-HMPAO) labeled leukocytes in children with suspected IBD. MATERIAL AND METHODS: Eighty-five children (age 12.4 ± 4.3 years, 47% boys) with suspected IBD based on clinical presentation, laboratory and ultrasound findings underwent scintigraphy with 99mTc-HMPAO labeled leukocytes. Abdominal scintigrams were acquired 40 min and 90 min post injection, and whole body scintigrams at 180 min. Scintigraphy was evaluated by two specialists in nuclear medicine. The results were compared with the final diagnosis established by endoscopy, histology, other imaging methods, and follow-up evaluated by an expert in pediatric gastroenterology. RESULTS: Scintigraphy results corresponded with the final diagnosis in 78 (91%) patients resulting in a sensitivity of 89% (95%CI 72 to 98%), specificity of 91% (95% CI 82 to 98%), and accuracy of 91% (95% CI 83 to 96%). The interobserver agreement was 0.82 (95% CI 0.75 to 0.88) and the radiation dose estimate was 4.2 ± 1.5 mSv. In 28 children (25 positives and 3 negatives on scintigraphy), the diagnosis of IBD was established by endoscopy, histology, MR enterography, or fluoroscopy. Five positive findings on scintigraphy were not confirmed by other methods or during follow-up. CONCLUSION: Scintigraphy with 99mTc-HMPAO labeled leukocytes in children with suspected IBD has high accuracy and offers a non-invasive option for detecting the presence of gastrointestinal inflammation. Scintigraphy is a powerful non-invasive decision-making tool in the management of suspected IBD that may spare a greater proportion of children of more invasive and demanding examinations.

How to recognize stent graft infection after endovascular aortic repair: the utility of 18F-FDG PET/CT in an infrequent but serious clinical setting.

OBJECTIVE: To evaluate the diagnostic performance of 18F-FDG PET/CT in the detection of stent graft infection (SGI). METHODS: In a retrospective study, two nuclear medicine physicians have independently analyzed 17 18F-FDG PET/CT examinations performed for clinical suspicion of SGI. The images were evaluated for the uptake pattern and intensity, and by the maximum standard uptake value (SUVmax), the target-to-background ratio with blood pool (TBRBP) and liver uptake (TBRhep) as a reference. The SGI was defined as the presence of focal hyperactivity with an intensity exceeding hepatic uptake. CT images were independently assessed for signs of SGI. Clinical review of all further patients' data served as the standard of reference. RESULTS: Nine cases were established as SGI by the clinical review. PET/CT correctly diagnosed SGI in eight and yielded a sensitivity of 89% and specificity of 100%. The mean SUVmax, TBRBP, and TBRhep values were 9.8 ± 4.0, 6.9 ± 2.6, and 4.6 ± 1.7 in the group of patients with true SGI, and 4.0 ± 1.1, 2.5 ± 0.4 (p < 0.001) and 1.9 ± 0.2 (p < 0.001) in true negative cases, respectively. CT alone showed a sensitivity of 78% and specificity of 100% and was concordant with PET/CT in 14 cases. The best performing threshold values of SUVmax, TBRBP, and TBRhep were 5.6, 3.5, and 2.2, respectively. CONCLUSION: 18F-FDG PET/CT with expert evaluation, semiquantitative and quantitative image analysis with the proposed threshold values for SUVmax, TBRBP, and TBRhep has good diagnostic accuracy in the detection of SGI. We propose that visual grading scale for SGI should use hepatic uptake as a visual reference.

Relations of non-motor symptoms and dopamine transporter binding in REM sleep behavior disorder.

The aim of this study was to evaluate associations of motor and non-motor symptoms with dopamine transporter binding in prodromal stage of synucleinopathies. We examined 74 patients with idiopathic REM sleep behavior disorder (RBD), which is a prodromal synucleinopathy, and 39 controls using Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS), Montreal Cognitive Assessment, University of Pennsylvania Smell Identification Test (UPSIT), Farnsworth-Munsell 100 hue test, orthostatic test, Scales for Outcomes in PD-Autonomic, Beck depression inventory-II, State-Trait Anxiety Inventory, and video-polysomnography. Electromyographic muscle activity during REM sleep was quantified according to Sleep Innsbruck-Barcelona criteria. In 65 patients, dopamine transporter single-photon emission computed tomography (DAT-SPECT) imaging was performed, putaminal binding ratio was calculated and scans were classified as normal, borderline, or abnormal. Compared to controls, RBD patients had significantly more severe scores in all examined tests. Patients with abnormal DAT-SPECT had higher MDS-UPDRS motor score (p = 0.006) and higher prevalence of orthostatic hypotension (p = 0.008). Putaminal binding ratio was positively associated with UPSIT score (p = 0.03) and negatively associated with tonic (p = 0.003) and phasic (p = 0.01) muscle activity during REM sleep. These associations likely reflect simultaneous advancement of underlying pathology in substantia nigra and susceptible brainstem and olfactory nuclei in prodromal synucleinopathy.

Prospective memory impairment in idiopathic REM sleep behavior disorder.

OBJECTIVE: The aim of the present study was to investigate if prospective memory (PM) is impaired in idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD). RBD is a parasomnia characterized by dream enactment and by REM sleep without muscle atonia. iRBD is considered as the initial stage of neurodegeneration with pathological storage of alpha-synuclein. METHOD: Sixty iRBD patients with polysomnography-confirmed RBD without parkinsonism and dementia and 30 demographically matched normal controls (NC) were enrolled in the present study. Clinical assessment included Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS), dopamine transporter single-photon emission computed tomography (DaT-SPECT) for imaging synapses of dopaminergic neurons in the striatum and a neuropsychological battery with embedded time-based and event-based PM measures. RESULTS: iRBD differed significantly from NC in event-based PM, a number of event-based failures to recall intention and total PM performance (all p < .001) but did not differ in time-based PM and recognition. PM did not contribute to impairment of instrumental activities of daily living in iRBD. Despite being preserved in iRBD in comparison to NC, time-based PM correlated significantly with dopaminergic neuronal loss measured by DaT-SPECT. CONCLUSIONS: We show evidence for a differential pattern of PM impairment in iRBD with severe impairment of event-based and concurrent preservation of time-based PM. We theorize that event-based PM impairment in iRBD is caused by severe impairment of retention and recognition mechanisms in episodic memory whereas time-based PM seems to be affected by reduced striatal dopaminergic synapses.

MCNP-based computational model for the Leksell gamma knife.

We have focused on the usage of MCNP code for calculation of Gamma Knife radiation field parameters with a homogenous polystyrene phantom. We have investigated several parameters of the Leksell Gamma Knife radiation field and compared the results with other studies based on EGS4 and PENELOPE code as well as the Leksell Gamma Knife treatment planning system Leksell GammaPlan (LGP). The current model describes all 201 radiation beams together and simulates all the sources in the same time. Within each beam, it considers the technical construction of the source, the source holder, collimator system, the spherical phantom, and surrounding material. We have calculated output factors for various sizes of scoring volumes, relative dose distributions along basic planes including linear dose profiles, integral doses in various volumes, and differential dose volume histograms. All the parameters have been calculated for each collimator size and for the isocentric configuration of the phantom. We have found the calculated output factors to be in agreement with other authors' works except the case of 4 mm collimator size, where averaging over the scoring volume and statistical uncertainties strongly influences the calculated results. In general, all the results are dependent on the choice of the scoring volume. The calculated linear dose profiles and relative dose distributions also match independent studies and the Leksell GammaPlan, but care must be taken about the fluctuations within the plateau, which can influence the normalization, and accuracy in determining the isocenter position, which is important for comparing different dose profiles. The calculated differential dose volume histograms and integral doses have been compared with data provided by the Leksell GammaPlan. The dose volume histograms are in good agreement as well as integral doses calculated in small calculation matrix volumes. However, deviations in integral doses up to 50% can be observed for large volumes such as for the total skull volume. The differences observed in treatment of scattered radiation between the MC method and the LGP may be important in this case. We have also studied the influence of differential direction sampling of primary photons and have found that, due to the anisotropic sampling, doses around the isocenter deviate from each other by up to 6%. With caution about the details of the calculation settings, it is possible to employ the MCNP Monte Carlo code for independent verification of the Leksell Gamma Knife radiation field properties.

Comparison of planar DMSA scan with an evaluation based on SPECT imaging in the split renal function assessment.

BACKGROUND: Validation of the 99mTc-DMSA planar scintigraphy accuracy for split renal function assessment and comparison with evaluation based on SPECT imaging both with and without CT attenuation correction. MATERIALS AND METHODS: For split renal function assessment two methods were used: A) planar scintigraphy based on anterior and posterior projections using correction for kidney depth calculated by the geometric mean; B) semi-quantitative evaluation based on SPECT (B1) and attenuation-corrected SPECT/CT (B2) images using locally developed software for kidney segmentation and voxel-based analysis. All three methods were performed with a phantom simulating body including pair of kidneys. For patient study methods A and B1 were applied on a group of 140 children and adolescents with various renal diseases. Renal function ratios were compared both mutually and with physically measured activity ratios in the phantom. RESULTS: Method A provided results which were closest to measured reference values (average absolute difference of 0.9 percentage points [pp]). Method B1 was noticeably worse (2.1pp), whereas attenuation correction (B2) improved tomography results considerably (1.3 pp). The superiority of planar imaging could be caused among others by differences in creation of planar range of interest compared to tomographic volume of interest. However all the differences were under the threshold of any clinical importance. The comparison between method A and B1 based on patient study also showed differences mostly of none clinical importance. CONCLUSION: Routine evaluation of split renal function using planar technique with correction of the kidney depth is at least equivalent to tomographic evaluation, and there is no need to update the established clinical practice.