Long-term prosthetic-associated subclinical thrombotic events evaluation by cardiac CTA after transcatheter aortic valve implantation: incidence and outcomes.

OBJECTIVE: To observe prosthetic-associated subclinical thrombotic events (PASTE) after transcatheter aortic valve implantation (TAVI) by cardiac CTA, and assess their impact on long-term patient outcomes. MATERIALS: We prospectively and consecutively enrolled 188 patients with severe aortic stenosis treated with TAVI from February 2014 to April 2017. At 5 years, 61 of 141 survived patients who had completed annual follow-up CTA (≥ 5 years) were included. We analyzed PASTE by CTA, including hypoattenuated leaflet thickening (HALT), sinus filling defect (SFD), and prosthesis filling defect (PFD). The primary outcome was a major adverse cardiovascular composite outcome (MACCO) of stroke, cardiac re-hospitalization, and bioprosthetic valve dysfunction (BVD); the secondary outcomes were bioprosthetic hemodynamics deterioration (PGmean) and cardiac dysfunction (LVEF). RESULTS: During a median follow-up time of 5.25 years, long-term incidence of HALT, SFD, and PFD were 54.1%, 37.7%, and 73.8%, respectively. In the primary outcome, SFD and early SFD were associated with the MACCO (SFD: p = 0.005; early SFD: p = 0.018), and SFD was a predictor of MACCO (HR: 2.870; 95% CI: 1.010 to 8.154, p = 0.048). In the secondary outcomes, HALT was associated with increased PGmean (p = 0.031), while persistent HALT was correlated with ΔPGmean (ß = 0.38, p = 0.035). SFD was negatively correlated with ΔLVEF (ß = -0.39, p = 0.041), and early SFD was negatively correlated with LVEF and ΔLVEF (LVEF: r = -0.50, p = 0.041; ΔLVEF: r = -0.53, p = 0.030). CONCLUSIONS: PASTE were associated with adverse long-term outcomes, bioprosthetic hemodynamics deterioration, and cardiac dysfunction. In particular, SFD was a predictor of MACCO and may be a potential target for anticoagulation after TAVI (NCT02803294). REGISTRATION: URL: https://www. CLINICALTRIALS: gov ; Unique identifier: NCT02803294. CRITICAL RELEVANCE STATEMENT: PASTE, especially SFD, after TAVI based on cardiac CTA findings impacts the long-term outcomes of patients which is a predictor of long-term major adverse outcomes in patients and may be a potential target for anticoagulation after TAVI. KEY POINTS: Transcatheter aortic valve implantation is being used more often; associated subclinical thromboses have not been thoroughly evaluated. Prosthetic-associated subclinical thrombotic events were associated with adverse outcomes, bioprosthetic hemodynamics deterioration, and cardiac dysfunction. Studies should be directed at these topics to determine if they should be intervened upon.

Assessing the Role of Locus Coeruleus Degeneration in Essential Tremor and Parkinson's Disease with Sleep Disorders.

Background: Previous studies have demonstrated the importance of the locus coeruleus (LC) in sleep-wake regulation. Both essential tremor (ET) and Parkinson's disease (PD) share common sleep disorders, such as poor quality of sleep (QoS). LC pathology is a feature of both diseases. A question arises regarding the contribution of LC degeneration to the occurrence of poor QoS. Objective: To evaluate the association between LC impairment and sleep disorders in ET and PD patients. Methods: A total of 83 patients with ET, 124 with PD, and 83 healthy individuals were recruited and divided into ET/PD with/without poor QoS (Sle/NorET and Sle/NorPD) subgroups according to individual Pittsburgh Sleep Quality Index (PSQI) score. Neuromelanin-sensitive magnetic resonance imaging (NM-MRI) and free-water imaging derived from diffusion MRI were performed. Subsequently, we evaluated the association between contrast-to-noise ratio of LC (CNRLC) and free-water value of LC (FWLC) with PSQI scores in ET and PD groups. Results: CNRLC was significantly lower in ET (p = 0.047) and PD (p = 0.018) than in healthy individuals, whereas no significant difference was found in FWLC among the groups. No significant differences were observed in CNR/FWLC between patients with/without sleep disorders after multiple comparison correction. No correlation was identified between CNR/FWLC and PSQI in ET and PD patients. Conclusions: LC degeneration was observed in both ET and PD patients, implicating its involvement in the pathophysiology of both diseases. Additionally, no significant association was observed between LC integrity and PSQI, suggesting that LC impairment might not directly relate to overall QoS.

The longitudinal volumetric and shape changes of subcortical nuclei in Parkinson's disease.

Brain structural changes in Parkinson's disease (PD) are progressive throughout the disease course. Changes in surface morphology with disease progression remain unclear. This study aimed to assess the volumetric and shape changes of the subcortical nuclei during disease progression and explore their association with clinical symptoms. Thirty-four patients and 32 healthy controls were enrolled. The global volume and shape of the subcortical nuclei were compared between patients and controls at baseline. The volume and shape changes of the subcortical nuclei were also explored between baseline and 2 years of follow-up. Association analysis was performed between the volume of subcortical structures and clinical symptoms. In patients with PD, there were significantly atrophied areas in the left pallidum and left putamen, while in healthy controls, the right putamen was dilated compared to baseline. The local morphology of the left pallidum was correlated with Mini Mental State Examination scores. The left putamen shape variation was negatively correlated with changes in Unified Parkinson's Disease Rating Scale PART III scores. Local morphological atrophy of the putamen and pallidum is an important pathophysiological change in the development of PD, and is associated with motor symptoms and cognitive status in patients with PD.

Differential influences of rest tremor on brain fiber architecture in essential tremor and Parkinson's disease.

BACKGROUND: Rest tremor is a movement disorder commonly found in diseases like Parkinson's disease (PD) and essential tremor (ET). Rest tremor typically shows slower progression in PD, but more severe progression in ET. However, the underlying white matter organization of rest tremor behind PD and ET remains unclear. METHODS: This study included 57 ET patients (40 without rest tremor (ETWR), 17 with rest tremor (ETRT)), 68 PD patients (34 without rest tremor (PDWR), 34 with rest tremor (PDRT)), and 62 normal controls (NC). Fixel-based analysis was used to evaluate the structural changes of white matter in rest tremor in these different diseases. RESULTS: The fiber-bundle cross-section (FC) of the right non-decussating dentato-rubro-thalamic tract and several fibers outside the dentato-rubro-thalamic pathway in ETWR were significantly higher than that in NC. The fiber density and cross-section of the left nigro-pallidal in PDWR is significantly lower than that in NC, while the FC of bilateral nigro-pallidal in PDRT is significantly lower than that in NC. CONCLUSION: ET patients with pure action tremor showed over-activation of fiber tracts. However, when superimposed with rest tremor, ET patients no longer exhibited over-activation of fiber tracts, but rather showed a trend of fiber tract damage. Except for the nigro-pallidal degeneration in all PD, PDRT will not experience further deterioration in fiber organization. These results provide important insights into the unique effects of rest tremor on brain fiber architecture in ET and PD.

Microstructural alterations of the hypothalamus in Parkinson's disease and probable REM sleep behavior disorder.

BACKGROUND: Whether there is hypothalamic degeneration in Parkinson's disease (PD) and its association with clinical symptoms and pathophysiological changes remains controversial. OBJECTIVES: We aimed to quantify microstructural changes in hypothalamus using a novel deep learning-based tool in patients with PD and those with probable rapid-eye-movement sleep behavior disorder (pRBD). We further assessed whether these microstructural changes associated with clinical symptoms and free thyroxine (FT4) levels. METHODS: This study included 186 PD, 67 pRBD, and 179 healthy controls. Multi-shell diffusion MRI were scanned and mean kurtosis (MK) in hypothalamic subunits were calculated. Participants were assessed using Unified Parkinson's Disease Rating Scale (UPDRS), RBD Questionnaire-Hong Kong (RBDQ-HK), Hamilton Depression Rating Scale (HAMD), and Activity of Daily Living (ADL) Scale. Additionally, a subgroup of PD (n = 31) underwent assessment of FT4. RESULTS: PD showed significant decreases of MK in anterior-superior (a-sHyp), anterior-inferior (a-iHyp), superior tubular (supTub), and inferior tubular hypothalamus when compared with healthy controls. Similarly, pRBD exhibited decreases of MK in a-iHyp and supTub. In PD group, MK in above four subunits were significantly correlated with UPDRS-I, HAMD, and ADL. Moreover, MK in a-iHyp and a-sHyp were significantly correlated with FT4 level. In pRBD group, correlations were observed between MK in a-iHyp and UPDRS-I. CONCLUSIONS: Our study reveals that microstructural changes in the hypothalamus are already significant at the early neurodegenerative stage. These changes are associated with emotional alterations, daily activity levels, and thyroid hormone levels.

Neuroimaging of Parkinson's disease by quantitative susceptibility mapping.

Parkinson's disease (PD) is a common neurodegenerative disease, and apart from a few rare genetic causes, its pathogenesis remains largely unclear. Recent scientific interest has been captured by the involvement of iron biochemistry and the disruption of iron homeostasis, particularly within the brain regions specifically affected in PD. The advent of Quantitative Susceptibility Mapping (QSM) has enabled non-invasive quantification of brain iron in vivo by MRI, which has contributed to the understanding of iron-associated pathogenesis and has the potential for the development of iron-based biomarkers in PD. This review elucidates the biochemical underpinnings of brain iron accumulation, details advancements in iron-sensitive MRI technologies, and discusses the role of QSM as a biomarker of iron deposition in PD. Despite considerable progress, several challenges impede its clinical application after a decade of QSM studies. The initiation of multi-site research is warranted for developing robust, interpretable, and disease-specific biomarkers for monitoring PD disease progression.

Multi-scale consistent self-training network for semi-supervised orbital tumor segmentation.

PURPOSE: Segmentation of orbital tumors in CT images is of great significance for orbital tumor diagnosis, which is one of the most prevalent diseases of the eye. However, the large variety of tumor sizes and shapes makes the segmentation task very challenging, especially when the available annotation data is limited. METHODS: To this end, in this paper, we propose a multi-scale consistent self-training network (MSCINet) for semi-supervised orbital tumor segmentation. Specifically, we exploit the semantic-invariance features by enforcing the consistency between the predictions of different scales of the same image to make the model more robust to size variation. Moreover, we incorporate a new self-training strategy, which adopts iterative training with an uncertainty filtering mechanism to filter the pseudo-labels generated by the model, to eliminate the accumulation of pseudo-label error predictions and increase the generalization of the model. RESULTS: For evaluation, we have built two datasets, the orbital tumor binary segmentation dataset (Orbtum-B) and the orbital multi-organ segmentation dataset (Orbtum-M). Experimental results on these two datasets show that our proposed method can both achieve state-of-the-art performance. In our datasets, there are a total of 55 patients containing 602 2D images. CONCLUSION: In this paper, we develop a new semi-supervised segmentation method for orbital tumors, which is designed for the characteristics of orbital tumors and exhibits excellent performance compared to previous semi-supervised algorithms.

Neurovascular coupling alteration in drug-naïve Parkinson's disease: The underlying molecular mechanisms and levodopa's restoration effects.

BACKGROUND: Parkinson's disease (PD) patients exhibit an imbalance between neuronal activity and perfusion, referred to as abnormal neurovascular coupling (NVC). Nevertheless, the underlying molecular mechanism and how levodopa, the standard treatment in PD, regulates NVC is largely unknown. MATERIAL AND METHODS: A total of 52 drug-naïve PD patients and 49 normal controls (NCs) were enrolled. NVC was characterized in vivo by relating cerebral blood flow (CBF) and amplitude of low-frequency fluctuations (ALFF). Motor assessments and MRI scanning were conducted on drug-naïve patients before and after levodopa therapy (OFF/ON state). Regional NVC differences between patients and NCs were identified, followed by an assessment of the associated receptors/transporters. The influence of levodopa on NVC, CBF, and ALFF within these abnormal regions was analyzed. RESULTS: Compared to NCs, OFF-state patients showed NVC dysfunction in significantly lower NVC in left precentral, postcentral, superior parietal cortex, and precuneus, along with higher NVC in left anterior cingulate cortex, right olfactory cortex, thalamus, caudate, and putamen (P-value <0.0006). The distribution of NVC differences correlated with the density of dopaminergic, serotonin, MU-opioid, and cholinergic receptors/transporters. Additionally, levodopa ameliorated abnormal NVC in most of these regions, where there were primarily ALFF changes with limited CBF modifications. CONCLUSION: Patients exhibited NVC dysfunction primarily in the striato-thalamo-cortical circuit and motor control regions, which could be driven by dopaminergic and nondopaminergic systems, and levodopa therapy mainly restored abnormal NVC by modulating neuronal activity.

Brain Age Prediction Based on Quantitative Susceptibility Mapping Using the Segmentation Transformer.

The process of brain aging is intricate, encompassing significant structural and functional changes, including myelination and iron deposition in the brain. Brain age could act as a quantitative marker to evaluate the degree of the individual's brain evolution. Quantitative susceptibility mapping (QSM) is sensitive to variations in magnetically responsive substances such as iron and myelin, making it a favorable tool for estimating brain age. In this study, we introduce an innovative 3D convolutional network named Segmentation-Transformer-Age-Network (STAN) to predict brain age based on QSM data. STAN employs a two-stage network architecture. The first-stage network learns to extract informative features from the QSM data through segmentation training, while the second-stage network predicts brain age by integrating the global and local features. We collected QSM images from 712 healthy participants, with 548 for training and 164 for testing. The results demonstrate that the proposed method achieved a high accuracy brain age prediction with a mean absolute error (MAE) of 4.124 years and a coefficient of determination (R2) of 0.933. Furthermore, the gaps between the predicted brain age and the chronological age of Parkinson's disease patients were significantly higher than those of healthy subjects (P<0.01). We thus believe that using QSM-based predicted brain age offers a more reliable and accurate phenotype, with the potentiality to serve as a biomarker to explore the process of advanced brain aging.

Cholinergic basal forebrain system degeneration underlies postural instability/gait difficulty and attention impairment in Parkinson's disease.

BACKGROUND AND PURPOSE: The specific pathophysiological mechanisms underlying postural instability/gait difficulty (PIGD) and cognitive function in Parkinson's disease (PD) remain unclear. Both postural and gait control, as well as cognitive function, are associated with the cholinergic basal forebrain (cBF) system. METHODS: A total of 84 PD patients and 82 normal controls were enrolled. Each participant underwent motor and cognitive assessments. Diffusion tensor imaging was used to detect structural abnormalities in the cBF system. The cBF was segmented using FreeSurfer, and its fiber tract was traced using probabilistic tractography. To provide information on extracellular water accumulation, free-water fraction (FWf) was quantified. FWf in the cBF and its fiber tract, as well as cortical projection density, were extracted for statistical analyses. RESULTS: Patients had significantly higher FWf in the cBF (p < 0.001) and fiber tract (p = 0.021) than normal controls, as well as significantly lower cBF projection in the occipital (p < 0.001), parietal (p < 0.001) and prefrontal cortex (p = 0.005). In patients, a higher FWf in the cBF correlated with worse PIGD score (r = 0.306, p = 0.006) and longer Trail Making Test A time (r = 0.303, p = 0.007). Attentional function (Trail Making Test A) partially mediated the association between FWf in the cBF and PIGD score (indirect effect, a*b = 0.071; total effect, c = 0.256; p = 0.006). CONCLUSIONS: Our findings suggest that degeneration of the cBF system in PD, from the cBF to its fiber tract and cortical projection, plays an important role in cognitive-motor interaction.

The effect of dopamine replacement therapy on cortical structure in Parkinson's disease.

AIMS: To explore the cortical structural reorganization in Parkinson's disease (PD) patients under chronic dopamine replacement therapy (DRT) in cross-sectional and longitudinal data and determine whether these changes were associated with clinical alterations. METHODS: A total of 61 DRT-treated, 60 untreated PD patients, and 61 normal controls (NC) were retrospectively included. Structural MRI scans and neuropsychological tests were conducted. Cortical thickness and volume were extracted based on FreeSurfer and were analyzed using general linear model to find statistically significant differences among three groups. Correlation analyses were performed among significant cortical areas, medication treatment (duration and dosage), and neuropsychological tests. Longitudinal cortical structural changes of patients who initiated DRT were analyzed using linear mixed-effect model. RESULTS: Significant cortical atrophy was primarily observed in the prefrontal cortex in treated patients, including the cortical thickness of right pars opercularis and the volume of bilateral superior frontal cortex (SFC), left rostral anterior cingulate cortex (rACC), right lateral orbital frontal cortex, right pars orbitalis, and right rostral middle frontal cortex. A negative correlation was detected between the left SFC volume and levodopa equivalent dose (LED) (r = -0.316, p = 0.016), as well as the left rACC volume and medication duration (r = -0.329, p = 0.013). In the patient group, the left SFC volume was positively associated with digit span forward score (r = 0.335, p = 0.017). The left SFC volume reduction was longitudinally correlated with increased LED (standardized coefficient = -0.077, p = 0.001). CONCLUSION: This finding provided insights into the influence of DRT on cortical structure and highlighted the importance of drug dose titration in DRT.

Development of a Clinicopathological-Radiomics Model for Predicting Progression and Recurrence in Meningioma Patients.

RATIONALE AND OBJECTIVES: Tumor progression and recurrence（P/R）after surgical resection are common in meningioma patients and can indicate poor prognosis. This study aimed to investigate the values of clinicopathological information and preoperative magnetic resonance imaging (MRI) radiomics in predicting P/R and progression-free survival (PFS) in meningioma patients. METHODS AND MATERIALS: A total of 169 patients with pathologically confirmed meningioma were included in this study, 54 of whom experienced P/R. Clinicopathological information, including age, gender, Simpson grading, World Health Organization (WHO) grading, Ki-67 index, and radiotherapy history, as well as preoperative traditional radiographic findings and radiomics features for each MRI modality (T1-weighted, T2-weighted, and enhanced T1-weighted images) were initially extracted. After feature selection, the optimal performance was estimated among the models established using different feature sets. Finally, Cox survival analysis was further used to predict PFS. RESULTS: Ki-67 index, Simpson grading, WHO grading, and radiotherapy history were found to be independent predictors for P/R in the multivariate regression analysis. This clinicopathological model had an area under the curve (AUC) of 0.865 and 0.817 in the training and testing sets, respectively. The performance of the combined radiomics model reached 0.85 and 0.84, respectively. A clinicopathological-radiomics model was then established, which significantly improved the prediction of meningioma P/R (AUC = 0.93 and 0.88, respectively). Finally, the risk ratio was estimated for each selected feature, and the C-index of 0.749 was obtained. CONCLUSION: Radiomics signatures of preoperative MRI have the ability to predict meningioma at the risk of P/R. By integrating clinicopathological information, the best performance was achieved.

Sub-voxel quantitative susceptibility mapping for assessing whole-brain magnetic susceptibility from ages 4 to 80.

The evolution of magnetic susceptibility of the brain is mainly determined by myelin in white matter (WM) and iron deposition in deep gray matter (DGM). However, existing imaging techniques have limited abilities to simultaneously quantify the myelination and iron deposition within a voxel throughout brain development and aging. For instance, the temporal trajectories of iron in the brain WM and myelination in DGM have not been investigated during the aging process. This study aimed to map the age-related iron and myelin changes in the whole brain, encompassing myelin in DGM and iron deposition in WM, using a novel sub-voxel quantitative susceptibility mapping (QSM) method. To achieve this, a cohort of 494 healthy adults (18-80 years old) was studied. The sub-voxel QSM method was employed to obtain the paramagnetic and diamagnetic susceptibility based on the approximated R 2 ' map from acquired R 2 * map. The linear relationship between R 2 * and R 2 ' maps was established from the regression coefficients on a small cohort data acquired with both 3D gradient recalled echo data and R 2 mapping. Large cohort sub-voxel susceptibility maps were used to create longitudinal and age-specific atlases via group-wise registration. To explore the differential developmental trajectories in the DGM and WM, we employed nonlinear models including exponential and Poisson functions, along with generalized additive models. The constructed atlases reveal the iron accumulation in the posterior part of the putamen and the gradual myelination process in the globus pallidus with aging. Interestingly, the developmental trajectories show that the rate of myelination differs among various DGM regions. Furthermore, the process of myelin synthesis is paralleled by an associated pattern of iron accumulation in the primary WM fiber bundles. In summary, our study offers significant insights into the distinctive developmental trajectories of iron in the brain's WM and myelination/demyelination in the DGM in vivo. These findings highlight the potential of using sub-voxel QSM to uncover new perspectives in neuroscience and improve our understanding of whole-brain myelination and iron deposit processes across the lifespan.

Free water and iron content in the substantia nigra at different stages of Parkinson's disease.

PURPOSE: Abnormalities in free water (FW) and susceptibility values exist in the substantia nigra (SN) of patients with Parkinson's disease (PD), but their role in characterizing the disease processes remains uncertain. This study investigated these values at various SN locations and stages of PD, and their relationship with clinical symptoms. METHOD: FW and quantitative susceptibility mapping (QSM) values were evaluated in the anterior and posterior SN, along with swallow-tail-sign (STS) ratings, in patients with PD (early-stage: n = 39; middle-to-advanced-stage: n = 97) and healthy controls (n = 82). The correlation between these indices and motor and non-motor symptoms, and their capability to distinguish PD from healthy controls, were also examined. RESULTS: Increased FW in the anterior and posterior SN and increased QSM values in the posterior SN were observed in both early-stage and middle-to-advanced-stage PD patients (p < 0.05). However, there was no significant difference in FW, QSM values, or STS ratings among patients at different stages. FW and QSM values correlated with motor symptoms in middle-to-advanced-stage patients (p < 0.05), while STS ratings were associated with non-motor symptoms (p < 0.05). Additionally, combining FW and QSM values in the posterior SN with STS ratings in logistic regression showed better performance in distinguishing PD (area under curve = 0.931) compared to using STS ratings alone (area under curve = 0.880). CONCLUSIONS: Findings suggest elevated FW and iron content in PD at different stages, with dissociation in SN location between the two indices. Elevated signals are related to the motor symptom severity in middle-to-advanced-stage patients, and may have the potential for PD diagnosis and symptom assessment.

Predictability of inter-regional cerebral perfusion similarity on dopamine responsiveness and the moderation role of cognition in PD patients.

BACKGROUND: Large heterogeneity can be found in dopamine responsiveness of patients with Parkinson's disease (PD). Instantly and objectively understanding dopamine responsiveness of patients may help clinical practice. PURPOSE: This PD study explored the predictability of off-state inter-regional cerebral blood flow (CBF) perfusion similarity on patient's dopamine responsiveness and tested whether the predictive power could be moderated by patient's cognitive status. MATERIALS AND METHOD: The PD cohort with 192 patients (containing off state and on state (PD-off and PD-on)) and the normal control (NC) cohort with 92 subjects were included. The intra-individual CBF relative variation networks were constructed and compared between PD-off and PD-on, PD-off and NC to identify the alterations caused by dopamine depletion. Based on that, regression analysis of off-state inter-regional CBF perfusion similarity on patient's dopamine responsiveness was performed. Finally, moderation analysis was conducted to test the moderation role of cognition on the regression model. RESULTS: In the PD-off cohort, a total of 82 edges in the network were identified that affected by dopamine depletion. Off-state inter-regional CBF perfusion similarity was found that had a significant influence on patient's dopamine responsiveness. Cognitive status was validated that positively moderated the relationship between off-state inter-regional CBF perfusion similarity and dopamine responsiveness. CONCLUSION: Dopamine responsiveness of PD patient could be predicted by off-state inter-regional CBF perfusion similarity. Patient's cognitive status might have a positive moderation effect on his/her dopamine responsiveness.

Two distinct trajectories of clinical and neurodegeneration events in Parkinson's disease.

Increasing evidence suggests that Parkinson's disease (PD) exhibits disparate spatial and temporal patterns of progression. Here we used a machine-learning technique-Subtype and Stage Inference (SuStaIn) - to uncover PD subtypes with distinct trajectories of clinical and neurodegeneration events. We enrolled 228 PD patients and 119 healthy controls with comprehensive assessments of olfactory, autonomic, cognitive, sleep, and emotional function. The integrity of substantia nigra (SN), locus coeruleus (LC), amygdala, hippocampus, entorhinal cortex, and basal forebrain were assessed using diffusion and neuromelanin-sensitive MRI. SuStaIn model with above clinical and neuroimaging variables as input was conducted to identify PD subtypes. An independent dataset consisting of 153 PD patients and 67 healthy controls was utilized to validate our findings. We identified two distinct PD subtypes: subtype 1 with rapid eye movement sleep behavior disorder (RBD), autonomic dysfunction, and degeneration of the SN and LC as early manifestations, and cognitive impairment and limbic degeneration as advanced manifestations, while subtype 2 with hyposmia, cognitive impairment, and limbic degeneration as early manifestations, followed later by RBD and degeneration of the LC in advanced disease. Similar subtypes were shown in the validation dataset. Moreover, we found that subtype 1 had weaker levodopa response, more GBA mutations, and poorer prognosis than subtype 2. These findings provide new insights into the underlying disease biology and might be useful for personalized treatment for patients based on their subtype.

Aberrant dentato-rubro-thalamic pathway in action tremor but not rest tremor: A multi-modality magnetic resonance imaging study.

AIMS: The purpose of this study was to clarify the dentato-rubro-thalamic (DRT) pathway in action tremor in comparison to normal controls (NC) and disease controls (i.e., rest tremor) by using multi-modality magnetic resonance imaging (MRI). METHODS: This study included 40 essential tremor (ET) patients, 57 Parkinson's disease (PD) patients (29 with rest tremor, 28 without rest tremor), and 41 NC. We used multi-modality MRI to comprehensively assess major nuclei and fiber tracts of the DRT pathway, which included decussating DRT tract (d-DRTT) and non-decussating DRT tract (nd-DRTT), and compared the differences in DRT pathway components between action and rest tremor. RESULTS: Bilateral dentate nucleus (DN) in the ET group had excessive iron deposition compared with the NC group. Compared with the NC group, significantly decreased mean diffusivity and radial diffusivity were observed in the left nd-DRTT in the ET group, which were negatively correlated with tremor severity. No significant difference in each component of the DRT pathway was observed between the PD subgroup or the PD and NC. CONCLUSION: Aberrant changes in the DRT pathway may be specific to action tremor and were indicating that action tremor may be related to pathological overactivation of the DRT pathway.

Functional connectome predicting individual gait function and its relationship with molecular architecture in Parkinson's disease.

Gait impairment is a common symptom of Parkinson's disease (PD), but its neural signature remains unclear due to the interindividual variability of gait performance. Identifying a robust gait-brain correlation at the individual level would provide insight into a generalizable neural basis of gait impairment. In this context, this study aimed to detect connectome that can predict individual gait function of PD, and follow-up analyses assess the molecular architecture underlying the connectome by relating it to the neurotransmitter-receptor/transporter density maps. Resting-state functional magnetic resonance imaging was used to detect the functional connectome, and gait function was assessed via a 10 m-walking test. The functional connectome was first detected within drug-naive patients (N = 48) by using connectome-based predictive modeling following cross-validation and then successfully validated within drug-managed patients (N = 30). The results showed that the motor, subcortical, and visual networks played an important role in predicting gait function. The connectome generated from patients failed to predict the gait function of 33 normal controls (NCs) and had distinct connection patterns compared to NCs. The negative connections (connection negatively correlated with 10 m-walking-time) pattern of the PD connectome was associated with the density of the D2 receptor and VAChT transporter. These findings suggested that gait-associated functional alteration induced by PD pathology differed from that induced by aging degeneration. The brain dysfunction related to gait impairment was more commonly found in regions expressing more dopaminergic and cholinergic neurotransmitters, which may aid in developing targeted treatments.