Dietary Caffeine and Brain Dopaminergic Function in Parkinson Disease.

OBJECTIVE: This study was undertaken to investigate the effects of dietary caffeine intake on striatal dopamine function and clinical symptoms in Parkinson disease in a cross-sectional and longitudinal setting. METHODS: One hundred sixty-three early Parkinson disease patients and 40 healthy controls were investigated with [123I]FP-CIT single photon emission computed tomography, and striatal dopamine transporter binding was evaluated in association with the level of daily coffee consumption and clinical measures. After a median interval of 6.1 years, 44 patients with various caffeine consumption levels underwent clinical and imaging reexamination including blood caffeine metabolite profiling. RESULTS: Unmedicated early Parkinson disease patients with high coffee consumption had 8.3 to 15.4% lower dopamine transporter binding in all studied striatal regions than low consumers, after accounting for age, sex, and motor symptom severity. Higher caffeine consumption was further associated with a progressive decline in striatal binding over time. No significant effects of caffeine on motor function were observed. Blood analyses demonstrated a positive correlation between caffeine metabolites after recent caffeine intake and dopamine transporter binding in the ipsilateral putamen. INTERPRETATION: Chronic caffeine intake prompts compensatory and cumulative dopamine transporter downregulation, consistent with caffeine's reported risk reduction in Parkinson disease. However, this decline does not manifest in symptom changes. Transiently increased dopamine transporter binding after recent caffeine intake has implications for dopaminergic imaging guidelines. ANN NEUROL 2024;96:262-275.

Gastrointestinal Symptoms and Dopamine Transporter Asymmetry in Early Parkinson's Disease.

BACKGROUND: The neurophysiological correlates of gastrointestinal symptoms (GISs) in Parkinson's disease (PD) are not well understood. It has been proposed that in patients with a gastrointestinal origin of PD dopaminergic neurodegeneration would be more symmetric. OBJECTIVES: The aim is to assess the associations between GISs and asymmetry of nigrostriatal dopaminergic neurodegeneration in PD. METHODS: Ninety PD patients were assessed using motor and GIS scales and 123 I-FP-CIT SPECT. We calculated the asymmetry index and the predominant side of motor symptoms and dopamine transporter (DAT) imaging defect and assessed their association with GISs. RESULTS: There were no significant differences in GISs between symmetric and asymmetric dopaminergic defect. Left predominant defect was related to more GIS and higher constipation scores. CONCLUSIONS: GISs were associated with left predominant reduction in putaminal DAT binding but not asymmetry per se. It remains open whether left-sided DAT deficit is related to more pronounced GI involvement or symptom perception in PD. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson Movement Disorder Society.

Diagnostic value of micrographia in Parkinson's disease: a study with [123I]FP-CIT SPECT.

Micrographia is a common symptom of Parkinson's disease (PD), and it may precede other motor symptoms. Despite the high prevalence of micrographia in PD, its neurobiological mechanisms are not known. Given that levodopa may alleviate consistent micrographia and that nondopaminergic essential tremor (ET) is not associated with micrographia, micrographia could possibly be used as an ancillary diagnostic method that reflects nigrostriatal dopamine function. We evaluated the usefulness of micrographia as a simple one-sentence writing test in differentiating PD from ET. A total of 146 PD patients, 42 ET patients and 38 healthy controls provided writing samples and were scanned with brain [123I]FP-CIT dopamine transporter (DAT) SPECT imaging with ROI-based and voxelwise analyses. The diagnostic accuracy of micrographia was evaluated and compared to that of DAT binding. Compared to ET and healthy controls, PD patients showed micrographia (consistent, 25.6% smaller area of handwriting sample in PD compared to ET, p = 0.002, and 27.2% smaller area of handwriting compared to healthy controls, p = 0.004). PD patients showed 133% more severe progressive micrographia compared with ET patients (median b = - 0.14 in PD, b = - 0.06 in ET, p = 0.021). In early unmedicated cognitively normal patients, consistent micrographia showed 71.2% specificity and 87.5% sensitivity in PD versus ET differentiation, but micrographia had no correlation with striatal or extrastriatal [123I]FP-CIT binding in patients with PD. The one-sentence micrographia test shows moderately good accuracy in PD versus ET differentiation. The severity of micrographia has no relationship with DAT binding, suggesting nondopaminergic mechanism of micrographia in PD.ClinicalTrials.gov identifier: NCT02650843 (NMDAT study).

Diagnostic accuracy of glabellar tap sign for Parkinson's disease.

Glabellar tap or reflex (GR) is an old bedside clinical test used in the diagnostics of Parkinson's disease (PD), but its diagnostic value is unclear. This study examines the diagnostic validity and reliability of GR in PD in relation to brain dopaminergic activity. GR was performed on 161 patients with PD, 47 patients with essential tremor (ET) and 40 healthy controls immediately prior to dopamine transporter (DAT) [123I]FP-CIT SPECT scanning. The binding ratios were investigated with consideration of the GR result (normal/abnormal). In addition, the consistency of the GR was investigated with 89 patients after a mean follow-up of 2.2 years. PD and ET patients had higher GR scores than healthy controls (p < 0.001), but there was no difference in GR between PD and ET patients (p = 0.09). There were no differences in the ratio of abnormal to normal GRs between the PD and ET groups (73% vs. 64% abnormal, respectively, p = 0.13) or in DAT binding between PD patients with abnormal and normal GRs (p > 0.36). Over follow-up, the GR changed from abnormal to normal in 20% of PD patients despite the presence of clinically typical disease. The sensitivity and specificity of GR for differentiating PD from ET were 78.3% and 36.2%, respectively. Although GR has been used by clinicians in the diagnostics of PD, it does not separate PD from ET. It also shows considerable inconsistency over time, and abnormal GR has no relationship with dopamine loss. Its usefulness should be tested for other clinical diagnostic purposes.

A body-sized phantom for evaluation of diffusion-weighted MRI data using conventional, readout-segmented, and zoomed echo-planar sequences.

BACKGROUND: Abdominal diffusion-weighted imaging (DWI) has been rapidly increasing during the last few years. For the evaluation of new DWI techniques, the development of suitable phantoms and quality assurance methods is important. PURPOSE: To construct a body-diameter phantom for abdominal DWI and study the impact of different acquisition options on image quality. MATERIAL AND METHODS: A phantom with a diameter of 31 cm and a volume of 26 L was constructed, containing four samples representing a clinically relevant range of apparent diffusion coefficient (ADC) values. Measurements were carried out on 1.5T and 3.0T MRI systems using conventional echo-planar imaging (EPI), readout-segmented EPI, and zoomed EPI (3.0T) sequences. The effects of parallel imaging, coil intensity normalization, and patient-specific B1 shim (3.0T) were also examined. ADC values and signal-to-noise ratios of the samples were measured, and the level of artifacts was visually evaluated. RESULTS: The agreement of ADC values between different acquisition options was generally good, but higher values (by 0.07 × 10(-3) mm(2)/s on the average) with readout-segmented EPI as well as ADC variations of approximately 0.1 × 10(-3) mm(2)/s in slice direction were observed. The image artifacts were reduced by using patient-specific B1 shim, readout-segmented EPI, or zoomed EPI. CONCLUSION: The body-sized phantom demonstrated well the expected image artifacts in DWI with large field of view. The use of patient-specific B1 shim, readout-segmented EPI, or zoomed EPI improved image quality of DWI in this study.

Data quality in fMRI and simultaneous EEG-fMRI.

OBJECT: To evaluate functional magnetic resonance imaging (fMRI) and simultaneous electroencephalography (EEG)-fMRI data quality in an organization using several magnetic resonance imaging (MRI) systems. MATERIALS AND METHODS: Functional magnetic resonance imaging measurements were carried out twice with a uniform gel phantom on five different MRI systems with field strengths of 1.5 and 3.0 T. Several image quality parameters were measured with automatic analysis software. For simultaneous EEG-fMRI, data quality was evaluated on 3.0 T systems, and the phantom results were compared to data on human volunteers. RESULTS: The fMRI quality parameters measured with different MRI systems were on an acceptable level. The presence of the EEG equipment caused superficial artifacts on the phantom image. The typical artifact depth was 15 mm, and no artifacts were observed in the brain area in the images of volunteers. Average signal-to-noise ratio (SNR) reduction in the phantom measurements was 15 %, a reduction of SNR similar to that observed in the human data. We also detected minor changes in the noise of the EEG signal during the phantom measurement. CONCLUSION: The phantom proved valuable in the successful evaluation of the data quality of fMRI and EEG-fMRI. The results fell within acceptable limits. This study demonstrated a repeatable method to measure and follow up on the data quality of simultaneous EEG-fMRI.

Dopamine transporter binding in the brain is linked to irritable bowel syndrome in Parkinson's disease.

BACKGROUND: Gastrointestinal symptoms are common in Parkinson's disease (PD), but their neurophysiological correlates are not well understood. We recently reported that functional gastrointestinal symptoms were not associated with asymmetry per se but might be associated with lower left striatal dopamine transporter (DAT) binding. The purpose of this study was to further investigate if specific gastrointestinal symptoms associate with monoamine transporter changes in specific striatal or extrastriatal areas. METHODS: Ninety PD patients, who underwent DAT ¹2 3 I-FP-CIT SPECT imaging, were assessed using the MDS-Unified Parkinson's Disease Rating Scale part III, Rome III, and Wexner constipation score. DAT binding was calculated from striatal subregions using region-to-occipital cortex ratio. Voxel-wise analysis was used to assess the relationship between gastrointestinal symptoms and striatal DAT and extrastriatal serotonin transporter (SERT) binding. RESULTS: Irritable bowel syndrome (IBS) criteria were fulfilled in 17 patients and were linked to higher ¹2 3 I-FP-CIT binding in the right posterior putamen and adjacent areas as compared to patients without IBS. No other significant associations between gastrointestinal symptoms and DAT or SERT binding were found. CONCLUSIONS: These findings suggest that PD patients with IBS may have higher DAT binding in the right hemisphere. This finding implicates alterations of brain neurotransmitter physiology in the gastrointestinal symptoms of PD patients.

Convolutional neural networks for detection of transthyretin amyloidosis in 2D scintigraphy images.

BACKGROUND: Transthyretin amyloidosis (ATTR) is a progressive disease which can be diagnosed non-invasively using bone avid [99mTc]-labeled radiotracers. Thus, ATTR is also an occasional incidental finding on bone scintigraphy. In this study, we trained convolutional neural networks (CNN) to automatically detect and classify ATTR from scintigraphy images. The study population consisted of 1334 patients who underwent [99mTc]-labeled hydroxymethylene diphosphonate (HMDP) scintigraphy and were visually graded using Perugini grades (grades 0-3). A total of 47 patients had visual grade ≥ 2 which was considered positive for ATTR. Two custom-made CNN architectures were trained to discriminate between the four Perugini grades of cardiac uptake. The classification performance was compared to four state-of-the-art CNN models. RESULTS: Our CNN models performed better than, or equally well as, the state-of-the-art models in detection and classification of cardiac uptake. Both models achieved area under the curve (AUC) ≥ 0.85 in the four-class Perugini grade classification. Accuracy was good in detection of negative vs. positive ATTR patients (grade < 2 vs grade ≥ 2, AUC > 0.88) and high-grade cardiac uptake vs. other patients (grade < 3 vs. grade 3, AUC = 0.94). Maximum activation maps demonstrated that the automated deep learning models were focused on detecting the myocardium and not extracardiac features. CONCLUSION: Automated convolutional neural networks can accurately detect and classify different grades of cardiac uptake on bone scintigraphy. The CNN models are focused on clinically relevant image features. Automated screening of bone scintigraphy images using CNN could improve the early diagnosis of ATTR.

MRI quality assurance using the ACR phantom in a multi-unit imaging center.

BACKGROUND: Magnetic resonance imaging (MRI) instrumentation is vulnerable to technical and image quality problems, and quality assurance is essential. In the studied regional imaging center the long-term quality assurance has been based on MagNET phantom measurements. American College of Radiology (ACR) has an accreditation program including a standardized image quality measurement protocol and phantom. The ACR protocol includes recommended acceptance criteria for clinical sequences and thus provides possibility to assess the clinical relevance of quality assurance. The purpose of this study was to test the ACR MRI phantom in quality assurance of a multi-unit imaging center. MATERIAL AND METHODS: The imaging center operates 11 MRI systems of three major manufacturers with field strengths of 3.0 T, 1.5 T and 1.0 T. Images of the ACR phantom were acquired using a head coil following the ACR scanning instructions. Both ACR T1- and T2-weighted sequences as well as T1- and T2-weighted brain sequences in clinical use at each site were acquired. Measurements were performed twice. The images were analyzed and the results were compared with the ACR acceptance levels. RESULTS: The acquisition procedure with the ACR phantom was faster than with the MagNET phantoms. On the first and second measurement rounds 91% and 73% of the systems passed the ACR test. Measured slice thickness accuracies were not within the acceptance limits in site T2 sequences. Differences in the high contrast spatial resolution between the ACR and the site sequences were observed. In 3.0 T systems the image intensity uniformity was slightly lower than the ACR acceptance limit. CONCLUSION: The ACR method was feasible in quality assurance of a multi-unit imaging center and the ACR protocol could replace the MagNET phantom tests. An automatic analysis of the images will further improve cost-effectiveness and objectiveness of the ACR protocol.

Bile Reflux is a Common Finding in the Gastric Pouch After One Anastomosis Gastric Bypass.

INTRODUCTION: Data on postoperative bile reflux after one anastomosis gastric bypass (OAGB) is lacking. Bile reflux scintigraphy (BRS) has been shown to be a reliable non-invasive tool to assess bile reflux after OAGB. We set out to study bile reflux after OAGB with BRS and endoscopy in a prospective series (RYSA Trial). METHODS: Forty patients (29 women) underwent OAGB between November 2016 and December 2018. Symptoms were reported and upper gastrointestinal endoscopy (UGE) was done preoperatively. Six months after OAGB, bile reflux was assessed in UGE findings and as tracer activity found in gastric tube and esophagus in BRS (follow-up rate 95%). RESULTS: Twenty-six patients (68.4%) had no bile reflux in BRS. Twelve patients (31.6%) had bile reflux in the gastric pouch in BRS and one of them (2.6%) had bile reflux also in the esophagus 6 months postoperatively. Mean bile reflux activity in the gastric pouch was 5.2% (1-21%) of total activity. De novo findings suggestive of bile reflux (esophagitis, stomal ulcer, foveolar inflammation of gastric pouch) were found for 15 patients (39.5%) in postoperative UGE. BRS and UGE findings were significantly associated (P = 0.022). Eight patients experienced de novo reflux symptoms at 6 months, that were significantly associated with BRS and de novo UGE findings postoperatively (P = 0.033 and 0.0005, respectively). CONCLUSION: Postoperative bile reflux in the gastric pouch after OAGB is a common finding in scintigraphy and endoscopy. The long-term effects of bile exposure will be analyzed in future reports after a longer follow-up. TRIAL REGISTRATION: Clinical Trials Identifier NCT02882685.