Changes in the correlation between substantia nigra hyperechogenicity area and Parkinson's disease severity at different Hoehn and Yahr stages.

BACKGROUND: It is debatable whether the area of substantia nigra hyperechogenicity (SN+) in transcranial sonography (TCS) is related to Parkinson's disease (PD) severity. Iron deposition, which is associated with the formation of SN+, may have different effects on dopamine nerve function as PD progresses. However, little research has explored the association between the SN + area and disease severity of PD in stages. METHODS: 612 PD patients with sufficient bone window were retrospectively included from a PD database, and disease severity was assessed by the Unified Parkinson's Disease Rating Scale (UPDRS) scores. Based on the Hoehn and Yahr (H-Y) scale, we classified the patients into seven groups (H-Y stage 1, 1.5, 2, 2.5, 3, 4, and 5) and then analyzed the correlations between the SN + area and the UPDRS scores separately. RESULTS: Our results indicated a U-shaped relationship between the initial-SN + area and disease severity in PD: In the H-Y stage 1 group, the initial-SN + area was negatively correlated with the UPDRS total score (r = - 0.456, p < 0.001) and UPDRS-III score (r = - 0.497, p < 0.001). No correlation was observed in the groups of H-Y stages 1.5, 2, and 2.5. In the groups of H-Y stage ≥ 3, the initial-SN + area was positively correlated with the UPDRS total score and UPDRS-III score, with strongest correlation in the H-Y stage 5 group (all p values < 0.05). Moreover, the larger SN + area and average SN + area showed a similar evolutionary trend of correlation with UPDRS total score and UPDRS-III score. CONCLUSIONS: Our study indicated a U-shaped correlation between the SN + area with the UPDRS total score and UPDRS-III score as H-Y stage progressed. The evolution of the correlation may reflect the evolution of underlying pathological mechanisms related to iron deposition in the substantia nigra.

Prediction of Parkinson's disease by transcranial sonography-based deep learning.

OBJECTIVES: Transcranial sonography has been used as a valid neuroimaging tool to diagnose Parkinson's disease (PD). This study aimed to develop a modified transcranial sonography (TCS) technique based on a deep convolutional neural network (DCNN) model to predict Parkinson's disease. METHODS: This retrospective diagnostic study was conducted using 1529 transcranial sonography images collected from 854 patients with PD and 775 normal controls admitted to the Second Affiliated Hospital of Soochow University (Suzhou, Jiangsu, China) between September 2019 and May 2022. The data set was divided into training cohorts (570 PD patients and 541 normal controls), and the validation set (184 PD patients and 234 normal controls). Using these datasets, we developed four different DCNN models (ResNet18, ResNet50, ResNet152, and DenseNet121). We then assessed their diagnostic performance, including the area under the receiver operating characteristic (AUROC) curve, specificity, sensitivity, positive predictive value (PPV), negative predictive value (NPV), and F1 score and compared with traditional diagnostic criteria. RESULTS: Among the 1529 TCS images, 570 PD patients and 541 normal controls from 4 of 6 sonographers of the TCS team were selected as the training cohort, and 184 PD patients and 234 normal controls from the other 2 sonographers were chosen as the validation cohort. There were no sex and age differences between PD patients and normal control subjects in the training and validation cohorts (P values > 0.05). All DCNN models achieved good performance in distinguishing PD patients from normal control subjects on the validation datasets, with diagnostic AUROCs and accuracy of 0.949 (95% CI 0.925, 0.965) and 86.60 for the RestNet18 model, 0.949 (95% CI 0.929, 0.971) and 87.56 for ResNet50, 0.945 (95% CI 0.931, 0.969) and 88.04 for ResNet152, 0.953 (95% CI 0.935, 0.971) and 87.80 for DenseNet121, respectively. On the other hand, the diagnostic accuracy of the traditional diagnostic method was 82.30. The accuracy of all DCNN models was higher than that of traditional diagnostic method. Moreover, the 5k-fold cross-validation results in train datasets showed that these DCNN models are robust. CONCLUSION: The developed transcranial sonography-based DCNN models performed better than traditional diagnostic criteria, thus improving the sonographer's accuracy in diagnosing PD.

Correlation Between Substantia Nigra Hyperechogenicity and Iron Metabolism in the Postural Instability Gait Difficulty Subtype of Parkinson's Disease.

OBJECTIVE: The correlation between substantia nigra (SN) hyperechogenicity on transcranial sonography (TCS) and serum iron metabolism parameters in patients with the postural instability gait difficulty (PIGD) subtype of Parkinson's disease (PD) was investigated so as to explore the pathological mechanism of SN hyperechogenicity. METHODS: The study enrolled 95 PIGD patients recruited by the Parkinson's Disease Specialty in the Second Affiliated Hospital of Soochow University during June 2019-2021. On the basis of the TCS results, the PIGD patients were assigned to the PD with SN hyperechogenicity (SN+) group (n = 60) and PD without SN hyperechogenicity (SN-) group (n = 35). Meanwhile, 49 sex- and age-matched healthy individuals were included in the control group. All participants underwent blood tests. Differences in the iron metabolism parameters among the three groups and the correlation between SN hyperechogenicity and serum iron metabolism parameters were analyzed. RESULTS: Serum ferritin, ceruloplasmin and transferrin levels were lower in the SN+ and SN- groups than in the control group (all p values <0.001). The serum ceruloplasmin level was lower in the SN+ group (0.23 [0.20, 0.25] g/L) than in the SN- group (0.25 [0.22, 0.29] g/L) (p = 0.001), and the proportion of patients with an abnormal ceruloplasmin level was higher in the SN+ group than in the SN- group (43.3% [26/60] vs. 14.3% [5/35], χ2 = 8.484, p = 0.004). Moreover, the SN hyperechogenicity area was negatively correlated with the serum transferrin level (r = -0.428, p < 0.001). CONCLUSION: Decreased serum ceruloplasmin levels may be associated with SN hyperechogenicity development in PIGD patients. The SN hyperechogenicity area is negatively correlated with the serum transferrin level.

Clinical study of transcranial sonography image characteristics in patients with obstructive sleep apnea.

OBJECTIVE: This study aimed to explore the relationship between patients with obstructive sleep apnea (OSA) from subgroups of varying severity and substantia nigra (SN) hyperechogenicity as well as cerebral blood flow detected by transcranial sonography (TCS). The study also explored if there were differences in damage of the SN and in the cerebral blood flow between the bilateral sides. METHODS: Right-handed men diagnosed with OSA by polysomnography were recruited from August 2018 to August 2020. The included patients were divided into 3 subgroups (mild, moderate, and severe OSA), and all patients underwent TCS. RESULTS: Among the 157 study patients (30 with mild OSA, 25 moderate, and 102 severe), the overall prevalence of SN hyperechogenicity was 15% (23/157). The hyperechogenicity detection rates were 3% (4/157) in the right SN subgroup and 13% (20/157) in the left SN subgroup, which were significantly different. The left side always had reduced blood flow on TCS (P < 0.05). No correlation was observed between the severity of OSA and the detection rates of SN hyperechogenicity (P > 0.05). CONCLUSION: Patients with OSA showed a higher detection rate of SN hyperechogenicity on the left compared with the right side. The left middle cerebral arteries had reduced blood flow, which was consistent with the more severe damage of the left SN. No relationship was observed between the severity of OSA and the detection rate of SN hyperechogenicity or hemodynamic parameters.

Barbier polymerization induced emission of cinnamaldehyde: a one-pot Grignard reaction?

The Barbier reaction is generally regarded as a one-pot Grignard reaction. Here, the Grignard reaction of cinnamaldehyde is demonstrated to give a 1,2-addition product, while the Barbier reaction of cinnamaldehyde yields a macromolecule with interesting aggregation-induced emission type non-conjugated luminescence properties, which indicates that the Barbier reaction cannot be regarded as a one-pot Grignard reaction.

Association Between Asymmetry of Substantia Nigra Hyperechogenicity and Clinical Characteristics in Different Parkinson Disease Subtypes: A 5-Year Follow-up Study.

Our study focused on three aspects to determine whether bilateral substantia nigra hyperechogenicity (SN+) is asymmetrical, whether the asymmetry of SN+ is related to the clinical features and whether there is variation in SN+ asymmetry during the progression of Parkinson disease (PD). This follow-up study included 234 patients with PD, who were divided into tremor PD (TD, n = 67) and non-tremor PD (NTD, n = 167) groups based on the Unified Parkinson's Disease Rating Scale (UPDRS) Part III. All participants underwent transcranial sonography (TCS) and clinical assessment. In both the TD and NTD groups, the initial SN+ was larger than the non-initial SN+. The initial SN+ was associated with Hoehn and Yahr (H&Y) stage, PD duration and initial UPDRS III, and the SN+ asymmetry index was associated with motor asymmetry index in the TD group. In the NTD group, the initial SN+ was associated only with initial UPDRS III. After a 5-year follow-up, the area of SN+ on both sides was gradually inclining to symmetry in the NTD group. Our study determined that SN+ asymmetry could reflect asymmetrical characteristics of PD. Furthermore, we inferred that the dynamic change in SN+ asymmetry might reflect a dynamic change in motor asymmetry in the NTD group.

Barbier Hyperbranching Polymerization-Induced Emission from an AB-Type Monomer.

Luminescent polymer materials have gained considerable research efforts in the past decades and are generally molecular designed by extending the π system of the polymer main chain or by incorporating chromophores into the polymer chain, which suffer from poor solubility, difficult synthesis, or multi-step procedures. Meanwhile, according to the step-growth polymerization theory, synthesis of hyperbranched polymers from an AB-type monomer is still challenging. Herein, we report a one-pot synthesis of nonconjugated luminescent hyperbranched polymer material via Barbier hyperbranching polymerization-induced emission (PIE) from an AB-type monomer. The key step in the realization of the hyperbranched polymer is bi-functionalization of a mono-functional group. Through a Barbier reaction between an organohalide and an ester group in one pot, bi-functionalization of mono-functional ester is realized through two-step nucleophilic additions, resulting in hyperbranched polytriphenylmethanols (HPTPM). Attributed to through-space conjugation and inter- and intramolecular charge-transfer effects induced by polymer chain, nonconjugated HPTPMs are PIEgens, which are tunable by monomer structure and polymerization time. When all phenyl groups are rotatable, HPTPM is aggregation-induced emission type PIEgen. Whereas, it is aggregation-caused quenching type PIEgen if some phenyl groups are rotation forbidden. Further potential applications of PIEgen are in the fields of explosive detection and artificial light harvesting systems. This work, therefore, expands the monomer library and molecular design library of hyperbranched polymers through "bi-functionalization of mono-functional group" strategy, which eventually expands the preparation library of nonconjugated luminescent polymer materials through one-pot PIE from nonemissive monomer.

Living Covalent-Anionic-Radical Polymerization via a Barbier Strategy.

The developments of the living alkene polymerization method have achieved great progress and enabled the precise synthesis of important polyalkenes with controlled molecular weight, molecular weight distribution, and architecture through an anionic, cationic or radical strategy. However, it is still challenging to develop a living alkene polymerization method through an all-in-one strategy where anionic and radical characteristics are merged into one polymerization species. Here, a versatile living polymerization method is reported by introducing a well-established all-in-one covalent-anionic-radical Barbier strategy into a living polymerization. Through this living covalent-anionic-radical Barbier polymerization (Barbier CARP), narrow distributed polystyrenes, with D as low as 1.05, are successfully prepared under mild conditions with a full monomer conversion by using wide varieties of organohalides, for example, alkyl, benzyl, allyl, and phenyl halides, as initiators with Mg in one pot. This living covalent-anionic-radical polymerization via a Barbier strategy expands the methodology library of polymer chemistry and enables living polymerization with an unconventional polymerization mode.

Novel NBN-Embedded Polymers and Their Application as Fluorescent Probes in Fe3+ and Cr3+ Detection.

The isosteric replacement of C═C by B-N units in conjugated organic systems has recently attracted tremendous interest due to its desirable optical, electronic and sensory properties. Compared with BN-, NBN- and BNB-doped polycyclic aromatic hydrocarbons, NBN-embedded polymers are poised to expand the diversity and functionality of olefin polymers, but this new class of materials remain underexplored. Herein, a series of polymers with BNB-doped π-system as a pendant group were synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization from NBN-containing vinyl monomers, which was prepared via intermolecular dehydration reaction between boronic acid and diamine moieties in one pot. Poly{2-(4-Vinylphenyl)-2,3-dihydro-1H-naphtho[1,8-de][1,3,2]diazaborinine} (P1), poly{N-(4-(1H-naphtho[1,8-de][1,3,2]diazaborinin-2(3H)-yl)phenyl)acrylamide} (P2) and poly{N-(4-(1H-benzo[d][1,3,2]diazaborol-2(3H)-yl)phenyl)acrylamide} (P3) were successfully synthesized. Their structure, photophysical properties and application in metal ion detection were investigated. Three polymers exhibit obvious solvatochromic fluorescence. As fluorescent sensors for the detection of Fe3+ and Cr3+, P1 and P2 show excellent selectivity and sensitivity. The limit of detection (LOD) achieved by Fe3+ is 7.30 nM, and the LOD achieved by Cr3+ is 14.69 nM, which indicates the great potential of these NBN-embedded polymers as metal fluorescence sensors.

Association between homocysteine and third ventricle dilatation, mesencephalic area atrophy in Parkinson's disease with cognitive impairment.

OBJECTIVES: This study aimed to explore the association of homocysteine (Hcy) with third ventricle (V3) dilatation and mesencephalic area (MA) atrophy as determined by transcranial sonography (TCS) in Parkinson's disease (PD) with cognitive impairment. METHODS: The final statistical analysis included 101 PD patients and 20 age- and sex-matched controls. Using the Movement Disorder Society (MDS) level II criteria for PD with cognitive impairment, we categorized the PD patients into PD with normal cognition group (PD) and PD with cognitive impairment group (PDC). All subjects underwent TCS and laboratory analysis. RESULTS: The V3 width (r = 0.349, P = 0.005) and the MA (r = -0.484, P < 0.001) were significantly correlated with the Hcy concentration in the PDC patients. Binary logistic regression analysis revealed that age (OR [95% CI] = 1.114 [0.991-1.251], P = 0.002), and Hcy level (OR [95% CI] = 0.931 [0.752-1.153], P = 0.411) were independent risk factors for V3 dilatation. Hcy level (OR [95% CI] = 0.557 [0.323-0.967], P = 0.035) were independent risk factors for MA atrophy. After adjustment for confounding factors, the odds ratio of V3 dilatation was 3.50 (95% CI 1.054-11.399, P = 0.031) and the odds ratio of MA atrophy was 4.67 (95% CI 1.395-15.602, P = 0.012) in the patients with higher Hcy level compared with the lower level. CONCLUSIONS: The results revealed a close association between the V3 width, MA and Hcy concentration in PD patients with cognitive impairment. We hypothesized that increased Hcy concentration played a significant role in the development of brain atrophy in PD with cognitive impairment.

Shear wave elastography characteristics of upper limb muscle in rigidity-dominant Parkinson's disease.

BACKGROUND: Rigidity is one of the major manifestations of Parkinson's disease (PD), but no quantitative and objective imaging method has been developed to measure rigidity. Ultrasound shear wave elastography (SWE) can reflect the stiffness of tissue by providing a quantitative index. Thus, we conducted this study to evaluate the potential clinical value of SWE in assessing rigidity in PD. METHODS: A total of 63 subjects (44 patients with rigidity-dominant PD and 19 right-dominant-hand normal controls with matched age) were enrolled, and each underwent ultrasound SWE testing. The tests were conducted on the brachioradialis (BR) and biceps brachii (BB) on the more affected side in patients with PD and on the right side in normal controls. Differences in quantitative shear wave velocity (SWV) between patients with PD and normal controls were determined. The relationship of muscle SWV with joint rigidity, UPDRSIII, disease duration, sex, and age in patients with PD was analyzed. The intraclass correlation coefficient (ICC) was used to evaluate the reliability of SWE in assessing muscle stiffness in patients with PD. RESULTS: The mean SWVs of the BB and BR were higher in the PD group (3.65±0.46 and 4.62±0.89 m/s, respectively) than in normal controls (2.79±0.37 and 3.26±0.40 m/s, respectively). Stiffness in BR and BB was correlated with the upper-limb joint rigidity, UPDRSIII, and disease duration but not with sex or age in the PD group. The intraobserver correlation coefficients (ICCs) for interobserver and intraobserver variations in measuring SWV were 0.85 (95% confidence interval 0.56-0.95) and 0.85 (95% confidence interval 0.58-0.95), respectively, for BR and 0.90 (95% confidence interval 0.73-0.97) and 0.86 (95% confidence interval 0.61-0.95), respectively, for BB. CONCLUSIONS: SWV is associated with joint rigidity and disease duration, indicating that SWE can be potentially used as an objective and quantitative tool for evaluating rigidity.

Transcranial Sonographic Alterations of Substantia Nigra and Third Ventricle in Parkinson's Disease with or without Dementia.

BACKGROUND: Numerous studies have demonstrated that patients with Parkinson's disease (PD) have a higher prevalence of substantia nigra (SN) hyperechogenicity compared with controls. Our aim was to explore the neuroimaging characteristics of transcranial sonography (TCS) of patients with PD and those with PD with dementia (PDD). The correlation between the echogenicity of the SN and clinical symptoms in Chinese patients with PDD was also assessed. METHODS: The ratios of SN hyperechogenicity (SN+), maximum sizes of SN+, and widths of third ventricle (TV) were measured using TCS for all the recruited patients. Data were analyzed using one-way analysis of variance, rank-sum test, Chi-square test, and receiver-operating characteristic (ROC) curve analysis. RESULTS: The final statistical analysis included 46 PDD patients, 52 PD patients, and 40 controls. There were no significant differences in ratios of SN+ and maximum sizes of SN+ between PDD and PD groups (P > 0.05). TV widths were significantly larger in PDD group (7.1 ± 1.9 mm) than in PD group (6.0 ± 2.0 mm) and controls (5.9 ± 1.5 mm, P < 0.05); however, the ratios of enlarged TV did not differ among the three groups (P = 0.059). When cutoff value was set at 6.8 mm, the TV width had a relatively high sensitivity and specificity in discriminating between PDD and PD groups (P = 0.030) and between PDD group and controls (P = 0.003), based on ROC curve analysis. In PDD patients, SN+ was more frequently detected in akinetic-rigid subgroup, and patients with SN+ showed significantly higher Hoehn and Yahr stage and Nonmotor Symptoms Questionnaire scores (P < 0.05). CONCLUSIONS: Compared to Chinese patients with PD, patients with PDD had a wider TV, altered SN sonographic features, and more severe clinical symptoms. Our findings suggest that TCS can be used to assess brain atrophy in PD and may be useful in discriminating between PD with and without dementia.

Transcranial sonography image characteristics in different Parkinson's disease subtypes.

Recently, Parkinson's disease (PD) has been classified into three subtypes: postural instability gait difficulty (PIGD), tremor dominate (TD), and indeterminate PD. Transcranial sonography (TCS) is considered to be an important tool to diagnose PD. However, it is uncertain that whether there are differences in TCS image characteristics in different PD subtypes, so 373 idiopathic PD (188 PIGD, 108 TD, 77 indeterminate PD) were registered and received TCS in our investigation; also, the association between clinical characteristics and TCS results in different PD subtypes was analyzed. In accordance with several previous studies, we detected substantia nigra (SN) by TCS in 85.4% of patients with idiopathic PD; we concluded that PIGD patients had more serious disease than TD and indeterminate PD group (p < 0.05). They always had larger SN hyperechogenicity areas on TCS (p < 0.05), and we found that there was no correlation between SN hyperechogenicity and disease duration or severity (p > 0.05). Similarly, abnormal brainstem raphe signal was also more often in PIGD group than in TD and indeterminate PD group (p < 0.05), which might imply that PIGD group was vulnerable to suffer from depression in the future.

Sonographic Alteration of Basal Ganglia in Different Forms of Primary Focal Dystonia: A Cross-sectional Study.

BACKGROUND: Few studies have addressed whether abnormalities in the lenticular nucleus (LN) are characteristic transcranial sonography (TCS) echo features in patients with primary dystonia. This study aimed to explore alterations in the basal ganglia in different forms of primary focal dystonia. METHODS: cross-sectional observational study was performed between December 2013 and December 2014 in 80 patients with different forms of primary focal dystonia and 55 neurologically normal control subjects. TCS was performed in patients and control subjects. Multiple comparisons of multiple rates were used to compare LN hyperechogenicity ratios between control and patient groups. RESULTS: Thirteen individuals were excluded due to poor temporal bone windows, and two subjects were excluded due to disagreement in evaluation by sonologists. Totally, 70 patients (cervical dystonia, n = 30; blepharospasm, n = 30; oromandibular dystonia, n = 10) and 50 normal controls were included in the final analysis. LN hyperechogenicity was observed in 51% (36/70) of patients with primary focal dystonia, compared with 12% (6/50) of controls (P < 0.001). Substantia nigra hyperechogenicity did not differ between the two groups. LN hyperechogenicity was observed in 73% (22/30) of patients with cervical dystonia, a greater prevalence than in patients with blepharospasm (33%, 10/30, P = 0.002) and oromandibular dystonia (40%, 4/10, P = 0.126). LN hyperechogenicity was more frequently observed in patients with cervical dystonia compared with controls (73% vs. 12%, P < 0.001); however, no significant difference was detected in patients with blepharospasm (33% vs. 12%, P = 0.021) or oromandibular dystonia (40% vs. 12%, P = 0.088). CONCLUSIONS: LN hyperechogenicity is more frequently observed in patients with primary focal dystonia than in controls. It does not appear to be a characteristic TCS echo feature in patients with blepharospasm or oromandibular dystonia.

Alteration of brainstem raphe measured by transcranial sonography in depression patients with or without Parkinson's disease.

The purpose of our study was to assess the alteration of the brainstem raphe (BR) on transcranial sonography (TCS) in depression patients with or without Parkinson's disease (PD) and to explore whether the different changes of BR could reflect an increasing impairment of raphe structures. TCS was performed in patients with PD, depression with PD, depression only, and controls. Using the red nucleus as an internal standard, the BR was rated semi-quantitatively from grades 1-4 with grades 1-3 determined as abnormal. The rate of abnormal BR (≤grade 3) was found to be only 10 % in patients with PD (4/40) and 5 % in control patients (2/40). The rate of abnormal raphe was significantly higher (p < 0.05) in patients with both depression and PD (85 %, 34/40) or patients with depression only (87.5 %, 35/40). TCS of the raphe in most patients with mild depression scored grade 3, while those with moderate depression scored grade 2-3, and those with severe depression scored grade 1. The different BR echogenicity score reflected an increasing impairment of raphe structures in depression patients with or without PD (p < 0.05). TCS provides a good tool for assessing depression, more severe depressive symptoms were associated with different aspects in TCS studies.

Transcranial sonography on Parkinson's disease and essential tremor in a Chinese population.

We analyzed the results of transcranial sonography (TCS) on 110 Parkinson's disease (PD) patients, 30 essential tremor (ET) patients and 110 controls in a Chinese population and compared our findings to the previous literatures. The echo signal intensity of midbrain substantia nigra (SN) was measured and divided into grade I-V. If the high echo signal intensity (grade III, IV or V) was detected in either side of SN, it was measured as well as the whole area of midbrain and the ratio of both sides of SN hyperechogenicity to the whole area of midbrain (S/M) were calculated. In addition, the width of the third ventricle in the level of thalamus was also determined. There were more individuals with the grade of SN ≥ III in PD group (100/110, 85.45%) than these in ET group (4/30, 13.33%, x ( 2 ) = 58.38, P < 0.001) and control group (11/110, 10%, x ( 2 ) = 125.51, P < 0.001). The median and quartile range of SN hyperechogenicity area and S/M in PD patients were greater than those in ET patients and controls. Both the area of SN hyperechogenicity ≥0.2 cm(2) and the S/M ≥ 0.07 were useful indexes to distinguish PD and ET in Chinese population. In conclusion, TCS is an effective and useful tool to detect PD and to distinguish PD from ET in Chinese patients.