Parkinson's disease multimodal imaging: F-DOPA PET, neuromelanin-sensitive and quantitative iron-sensitive MRI.
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ABSTRACT:
SUBMITTER: Depierreux F
PROVIDER: S-EPMC8266835 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundNeuromelanin- and iron-sensitive MRI studies in Parkinson's disease (PD) are limited by small sample sizes and lack detailed clinical correlation. In a large case-control PD cohort, we evaluated the diagnostic accuracy of quantitative iron-neuromelanin MRI parameters from the substantia nigra (SN), their radiological utility, and clinical association.MethodsPD patients and age-matched controls were prospectively recruited for motor assessment and midbrain neuromelanin- and iron-sensitive [quantitative susceptibility mapping (QSM) and susceptibility map-weighted imaging (SMWI)] MRI. Quantitative neuromelanin-iron parameters from the SN were assessed for their discriminatory performance in PD classification using ROC analysis compared to those of qualitative visual classification by radiological readers of differential experience and used to predict motor severity.ResultsIn total, 191 subjects (80 PD, mean age 65.0 years; 111 controls, 65.6) were included. SN masks showed (a) higher mean susceptibility (p < 0.0001) and smaller sizes after thresholding for low susceptibility (p < 0.0001) on QSM and (b) lower contrast range (p < 0.0001) and smaller sizes after thresholding for high-signal voxels (p < 0.0001) on neuromelanin-sensitive MRI in patients than in controls. Quantitative iron and neuromelanin parameters showed a moderate correlation with motor dysfunction (87.5%: 0.4< | r | <0.6, p < 0.0001), respectively. A composite quantitative neuromelanin-iron marker differentiated the groups with excellent performance (AUC 0.94), matching the diagnostic accuracy of the best-performing reader (accuracy 97%) using SMWI.ConclusionQuantitative neuromelanin-iron MRI is associated with PD motor severity and matched best-performing radiological PD classification using SMWI, with the potential to improve diagnostic confidence in the clinics and track disease progression and response to neuroprotective therapies.
| S-EPMC10711072 | biostudies-literature
Project description:Recently, revised diagnostic criteria for Parkinson's disease (PD) were introduced (Postuma et al., 2015). Yet, except for well-established dopaminergic imaging, validated imaging biomarkers for PD are still missing, though they could improve diagnostic accuracy. We conducted systematic meta-analyses to identify PD-specific markers in whole-brain structural magnetic resonance imaging (MRI), [18F]-fluorodeoxyglucose-positron emission tomography (FDG-PET) and diffusion tensor imaging (DTI) studies. Overall, 74 studies were identified including 2323 patients and 1767 healthy controls. Studies were first grouped according to imaging modalities (MRI 50; PET 14; DTI 10) and then into subcohorts based on clinical phenotypes. To ensure reliable results, we combined established meta-analytical algorithms - anatomical likelihood estimation and seed-based D mapping - and cross-validated them in a conjunction analysis. Glucose hypometabolism was found using FDG-PET extensively in bilateral inferior parietal cortex and left caudate nucleus with both meta-analytic methods. This hypometabolism pattern was confirmed in subcohort analyses and related to cognitive deficits (inferior parietal cortex) and motor symptoms (caudate nucleus). Structural MRI showed only small focal gray matter atrophy in the middle occipital gyrus that was not confirmed in subcohort analyses. DTI revealed fractional anisotropy reductions in the cingulate bundle near the orbital and anterior cingulate gyri in PD. Our results suggest that FDG-PET reliably identifies consistent functional brain abnormalities in PD, whereas structural MRI and DTI show only focal alterations and rather inconsistent results. In conclusion, FDG-PET hypometabolism outperforms structural MRI in PD, although both imaging methods do not offer disease-specific imaging biomarkers for PD.
| S-EPMC6413303 | biostudies-literature
Project description:Background:Recent developments in magnetic resonance imaging (MRI) techniques have offered new research opportunities to visualize in vivo substantia nigra pathology in Parkinson's disease (PD). This paper summarizes the main findings of nigrosome imaging and neuromelanin sensitive MRI studies in patients with PD and other parkinsonisms. Methods:The PubMed database was searched from 2005 to 2017 using the following keywords: Parkinson's disease and parkinsonism, in combination with MRI, nigrosome, neuromelanin, and iron. Only publications in English were included. Results:Nigrosome or dorsal nigral hyperintensity abnormalities are studied using T2* and susceptibility weighted imaging MRI sequences in most studies, whereas Neuromelanin imaging is usually performed using T1-weighted fast spin echo sequence. Nigrosome abnormalities have been consistently demonstrated in PD patients, and nigrosome imaging has high sensitivity and specificity in distinguishing PD from healthy controls, though it is unable to reliably separate PD from atypical parkinsonisms. Reduced neuromelanin-related signals and/or volume loss in neuromelanin containing structures have been found in PD patients, and neuromelanin sensitive MRI imaging can also discriminate PD patients from healthy controls with high accuracy, though there is a degree of heterogeneity in the imaging findings. Preliminary findings suggested that longitudinal change of neuromelanin signal could be detected in PD, raising the possibility of using it as a marker of disease progression. Conclusion:Nigrosome imaging and neuromelanin sensitive MRI are promising tools to study nigral pathology and to improve the diagnosis of PD. However, further studies are required to standardize analysis approaches, confirm longitudinal changes, and assess their generalizability.
| S-EPMC6174398 | biostudies-literature
Project description:Neuromelanin sensitive magnetic resonance imaging (NMS-MRI) has been crucial in identifying abnormalities in the substantia nigra pars compacta (SNc) in Parkinson's disease (PD) as PD is characterized by loss of dopaminergic neurons in the SNc. Current techniques employ estimation of contrast ratios of the SNc, visualized on NMS-MRI, to discern PD patients from the healthy controls. However, the extraction of these features is time-consuming and laborious and moreover provides lower prediction accuracies. Furthermore, these do not account for patterns of subtle changes in PD in the SNc. To mitigate this, our work establishes a computer-based analysis technique that uses convolutional neural networks (CNNs) to create prognostic and diagnostic biomarkers of PD from NMS-MRI. Our technique not only performs with a superior testing accuracy (80%) as compared to contrast ratio-based classification (56.5% testing accuracy) and radiomics classifier (60.3% testing accuracy), but also supports discriminating PD from atypical parkinsonian syndromes (85.7% test accuracy). Moreover, it has the capability to locate the most discriminative regions on the neuromelanin contrast images. These discriminative activations demonstrate that the left SNc plays a key role in the classification in comparison to the right SNc, and are in agreement with the concept of asymmetry in PD. Overall, the proposed technique has the potential to support radiological diagnosis of PD while facilitating deeper understanding into the abnormalities in SNc.
| S-EPMC6417260 | biostudies-literature
Project description:Neuromelanin-sensitive magnetic resonance imaging quantitative analysis methods have provided promising biomarkers that can noninvasively quantify degeneration of the substantia nigra in patients with Parkinson's disease. However, there is a need to systematically evaluate the performance of manual and automated quantification approaches. We evaluate whether spatial, signal-intensity, or subject specific abnormality measures using either atlas based or manually traced identification of the substantia nigra better differentiate patients with Parkinson's disease from healthy controls using logistic regression models and receiver operating characteristics. Inference was performed using bootstrap analyses to calculate 95% confidence interval bounds. Pairwise comparisons were performed by generating 10,000 permutations, refitting the models, and calculating a paired difference between metrics. Thirty-one patients with Parkinson's disease and 22 healthy controls were included in the analyses. Signal intensity measures significantly outperformed spatial and subject specific abnormality measures, with the top performers exhibiting excellent ability to differentiate patients with Parkinson's disease and healthy controls (balanced accuracy = 0.89; area under the curve = 0.81; sensitivity =0.86; and specificity = 0.83). Atlas identified substantia nigra metrics performed significantly better than manual tracing metrics. These results provide clear support for the use of automated signal intensity metrics and additional recommendations. Future work is necessary to evaluate whether the same metrics can best differentiate atypical parkinsonism, perform similarly in de novo and mid-stage cohorts, and serve as longitudinal monitoring biomarkers.
| S-EPMC10789205 | biostudies-literature
Project description:Microstructural changes associated with degeneration of dopaminergic neurons of the substantia nigra pars compacta (SNc) in Parkinson's disease (PD) have been studied using Diffusion Tensor Imaging (DTI). However, these studies show inconsistent results, mainly due to methodological variations in delineation of SNc. To mitigate this, our work aims to construct a probabilistic atlas of SNc based on a 3D Neuromelanin Sensitive MRI (NMS-MRI) sequence and demonstrate its applicability to investigate microstructural changes on a large dataset of PD. Using manual segmentation and deformable registration we created a novel SNc atlas in the MNI space using NMS-MRI sequences of 27 healthy controls (HC). We first quantitatively evaluated this atlas and then employed it to investigate the micro-structural abnormalities in SNc using diffusion MRI from 133 patients with PD and 99 HCs. Our results demonstrated significant increase in diffusivity with no changes in anisotropy. In addition, we also observed an asymmetry of the diffusion metrics with a higher diffusivity and lower anisotropy in the left SNc than the right. Finally, a multivariate classifier based on SNc diffusion features could delineate patients with PD with an average accuracy of 71.7%. Overall, from this work we establish a normative baseline for the SNc region of interest using NMS-MRI while the application on PD data emphasizes on the contribution of diffusivity measures rather than anisotropy of white matter in PD.
| S-EPMC7267920 | biostudies-literature
Project description:Neuromelanin (NM) loss in substantia nigra pars compacta (SNc) and locus coeruleus (LC) reflects neuronal death in Parkinson's disease (PD). Since genetically-determined PD shows varied clinical expressivity, we wanted to accurately quantify and locate brainstem NM and iron, to discover whether specific MRI patterns are linked to Leucine-rich repeat kinase 2 G2019S PD (LRRK2-PD) or idiopathic Parkinson's disease (iPD). A 3D automated MRI atlas-based segmentation pipeline (3D-ABSP) for NM/iron-sensitive MRI images topographically characterized the SNc, LC, and red nucleus (RN) neuronal loss and calculated NM/iron contrast ratio (CR) and normalized volume (nVol). Left-side NM nVol was larger in all groups. PD had lower NM CR and nVol in ventral-caudal SNc, whereas iron increased in lateral, medial-rostral, and caudal SNc. The SNc NM CR reduction was associated with psychiatric symptoms. LC CR and nVol discriminated better among subgroups: LRRK2-PD had similar LC NM CR and nVol as that of controls, and larger LC NM nVol and RN iron CR than iPD. PD showed higher iron SNc nVol than controls, especially among LRRK2-PD. ROC analyses showed an AUC > 0.92 for most pairwise subgroup comparisons, with SNc NM being the best discriminator between HC and PD. NM measures maintained their discriminator power considering the subgroup of PD patients with less than 5 years of disease duration. The SNc iron CR and nVol increase was associated with longer disease duration in PD patients. The 3D-ABSP sensitively identified NM and iron MRI patterns strongly correlated with phenotypic PD features.
| S-EPMC10105708 | biostudies-literature
Project description:Noninvasive methods are needed to explore the heterogeneous tumor microenvironment and its modulation by therapy. Hybrid PET/MRI systems are being developed for small-animal and clinical use. The advantage of these integrated systems depends on their ability to provide MR images that are spatially coincident with simultaneously acquired PET images, allowing combined functional MRI and PET studies of intratissue heterogeneity. Although much effort has been devoted to developing this new technology, the issue of quantitative and spatial fidelity of PET images from hybrid PET/MRI systems to the tissues imaged has received little attention. Here, we evaluated the ability of a first-generation, small-animal MRI-compatible PET scanner to accurately depict heterogeneous patterns of radiotracer uptake in tumors.Quantitative imaging characteristics of the MRI-compatible PET (PET/MRI) scanner were evaluated with phantoms using calibration coefficients derived from a mouse-sized linearity phantom. PET performance was compared with a commercial small-animal PET system and autoradiography in tumor-bearing mice. Pixel and structure-based similarity metrics were used to evaluate image concordance among modalities. Feasibility of simultaneous PET/MRI functional imaging of tumors was explored by following (64)Cu-labeled antibody uptake in relation to diffusion MRI using cooccurrence matrix analysis.The PET/MRI scanner showed stable and linear response. Activity concentration recovery values (measured and true activity concentration) calculated for 4-mm-diameter rods within linearity and uniform activity rod phantoms were near unity (0.97 ± 0.06 and 1.03 ± 0.03, respectively). Intratumoral uptake patterns for both (18)F-FDG and a (64)Cu-antibody acquired using the PET/MRI scanner and small-animal PET were highly correlated with autoradiography (r > 0.99) and with each other (r = 0.97 ± 0.01). On the basis of these data, we performed a preliminary study comparing diffusion MRI and radiolabeled antibody uptake patterns over time and visualized movement of antibodies from the vascular space into the tumor mass.The MRI-compatible PET scanner provided tumor images that were quantitatively accurate and spatially concordant with autoradiography and the small-animal PET examination. Cooccurrence matrix approaches enabled effective analysis of multimodal image sets. These observations confirm the ability of the current simultaneous PET/MRI system to provide accurate observations of intratumoral function and serve as a benchmark for future evaluations of hybrid instrumentation.
| S-EPMC3552656 | biostudies-other
Project description:Background and purposeThe correlation between dopamine transporter (DAT) imaging and neuromelanin-sensitive magnetic resonance imaging (NM-MRI) in early-stage Parkinson's disease (PD) has not yet been established. This study aimed to determine the correlation between NM-MRI and DAT positron-emission tomography (PET) in patients with early-stage PD.MethodsFifty drug-naïve patients with early-stage PD who underwent both 0.8-mm isovoxel NM-MRI and DAT PET were enrolled retrospectively. Using four regions of interest (nigrosome 1 and nigrosome 2 [N1 and N2] regions) from a previous study, the contrast ratios (CRs) of 12 regions were measured: N1, N2, flipped N1, flipped N2, combined N1 and N2, and whole substantia nigra pars compacta [SNpc] (all on both sides). The clinically more affected side was separately assessed. The standardized uptake value ratios (SUVRs) were measured in the striatum using DAT PET. A partial correlation analysis was performed between the SUVR and CR measurements.ResultsCR of the flipped left N1 region was significantly correlated with SUVR of the right posterior putamen (p=0.047), and CR values of the left N1 region, left N2 region, flipped right N1 region, and combined left N1 and N2 regions were significantly correlated with SUVR of the left posterior putamen (p=0.011, 0.038, 0.020, and 0.010, respectively). SUVR of the left anterior putamen was significantly correlated with CR of the left N2 region (p=0.027). On the clinically more affected side, the CR values of the N1 region, combined N1 and N2 regions, and the whole SNpc were significantly correlated with SUVR of the posterior putamen (p=0.001, 0.024, and 0.021, respectively). There were significant correlations between the SUVR of the anterior putamen and the CR values of the N1 region, combined N1 and N2 regions, and whole SNpc (p=0.027, 0.001, and 0.036, respectively).ConclusionsThis study found that there were significant correlations between CR values in the SNpc on NM-MRI and striatal SUVR values on DAT PET on both sides in early-stage PD.
| S-EPMC9982185 | biostudies-literature
Project description:BackgroundNeuromelanin-sensitive magnetic resonance imaging techniques have been developed but currently require relatively long scan times. The aim of this study was to assess the ability of black-blood delay alternating with nutation for tailored excitation-prepared T1-weighted variable flip angle turbo spin echo (DANTE T1-SPACE), which provides relatively high resolution with a short scan time, to visualize neuromelanin in the substantia nigra pars compacta (SNpc).MethodsParticipants comprised 49 healthy controls and 25 patients with Parkinson's disease (PD). Contrast ratios of SNpc and hyperintense SNpc areas, which show pixels brighter than thresholds, were assessed between DANTE T1-SPACE and T1-SPACE in healthy controls. To evaluate the diagnostic ability of DANTE T1-SPACE, the contrast ratios and hyperintense areas were compared between healthy and PD groups, and receiver operating characteristic analyses were performed. We also compared areas under the curve (AUCs) between DANTE T1-SPACE and the previously reported gradient echo neuromelanin (GRE-NM) imaging. Each analysis was performed using original images in native space and images transformed into Montreal Neurological Institute space. Values of P < 0.05 were considered significant.ResultsDANTE T1-SPACE showed significantly higher contrast ratios and larger hyperintense areas than T1-SPACE. On DANTE T1-SPACE, healthy controls showed significantly higher contrast ratios and larger hyperintense areas than patients with PD. Hyperintense areas in native space analysis achieved the best AUC (0.94). DANTE T1-SPACE showed AUCs as high as those of GRE-NM.ConclusionsDANTE T1-SPACE successfully visualized neuromelanin of the SNpc and showed potential for evaluating PD. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
| S-EPMC8247273 | biostudies-literature