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Objective: This study aimed to examine the structural alterations of the deep gray matter (DGM) in the basal ganglia circuitry of Parkinson's disease (PD) patients with freezing of gait (FOG) using quantitative susceptibility mapping (QSM) and neuromelanin-sensitive magnetic resonance imaging (NM-MRI)., Methods: Twenty-five (25) PD patients with FOG (PD-FOG), 22 PD patients without FOG (PD-nFOG), and 30 age- and sex-matched healthy controls (HCs) underwent 3-dimensional multi-echo gradient recalled echo and NM-MRI scanning. The mean volume and susceptibility of the DGM on QSM data and the relative contrast (NM RC-SNpc ) and volume (NM volume-SNpc ) of the substantia nigra pars compacta on NM-MRI were analyzed among groups. A multiple linear regression analysis was performed to explore the associations of FOG severity with MRI measurements and disease stage., Results: The PD-FOG group showed higher susceptibility in the bilateral caudal substantia nigra (SN) compared to the HC group. Both the PD-FOG and PD-nFOG groups showed lower volumes than the HC group in the bilateral caudate and putamen as determined from the QSM data. The NM volume-SNpc on NM-MRI in the PD-FOG group was significantly lower than in the HC and PD-nFOG groups. Both the PD-FOG and PD-nFOG groups showed significantly decreased NM RC-SNpc ., Conclusions: The PD-FOG patients showed abnormal neostriatum atrophy, increases in iron deposition in the SN, and lower NM volume-SNpc . The structural alterations of the DGM in the basal ganglia circuits could lead to the abnormal output of the basal ganglia circuit to trigger the FOG in PD patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Increasing the signal-to-noise ratio (SNR) has always been of critical importance for magnetic resonance imaging. Although increasing field strength provides a linear increase in SNR, it is more and more costly as field strength increases. Therefore, there is a major effort today to use signal processing methods to improve SNR since it is more efficient and economical. There are a variety of methods to improve SNR such as averaging the data at the expense of imaging time, or collecting the data with a lower resolution, all of these methods, including imaging processing methods, usually come at the expense of loss of image detail or image blurring. Therefore, we developed a new mathematical approach called CROWN (Constrained Reconstruction of White Noise) to enhance SNR without loss of structural detail and without affecting scanning time. In this study, we introduced and tested the concept behind CROWN specifically for STAGE (strategically acquired gradient echo) imaging. The concept itself is presented first, followed by simulations to demonstrate its theoretical effectiveness. Then the SNR improvement on proton spin density (PSD) and R2 ⁎ maps was investigated using brain STAGE data acquired from 10 healthy controls (HCs) and 10 patients with Parkinson's disease (PD). For the PSD and R2* maps, the SNR and CNR between white matter and gray matter were improved by a factor of 1.87 ± 0.50 and 1.72 ± 0.88, respectively. The white matter hyperintensity lesions in PD patients were more clearly defined after CROWN processing. Using these improved maps, simulated images for any repeat time, echo time or flip angle can be created with improved SNR. The potential applications of this technology are to trade off the increased SNR for higher resolution images and/or faster imaging., Competing Interests: Declaration of competing interest A number of authors work for SpinTech MRI, otherwise there are no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Compared with MR plain scanning, gadolinium (Gd)-enhanced MR scanning can provide more diagnostic information. Gadopentetate dimeglumine is generally used as an MR enhancement contrast agent in some countries. It is a member of linear Gd-based contrast agents (GBCAs) which are considered more likely to release free Gd ions (Gd 3+ ) than macrocyclic GBCAs. Gd 3+ is one of the most effective known calcium antagonists, and can compete with calcium ions (Ca 2+ ) in Ca 2+ -related biological reactions. In this study, animal models of tissue regeneration were established by cutting the caudal fins of zebrafish, and the models were exposed with gadopentetate dimeglumine solution for different immersion times of 1, 3, and 5 min. Three GBCA exposures per week were performed in the first 3 weeks of the follow-up time. Morphological parameters such as regenerative area (RA), bone density, bone thickness and regenerative bone volume (RBV) were quantified using a camera and synchrotron radiation micro CT. RA decreased as total Gd intake increased in both the female group (ρ = -0.784, P < 0.0001) and the male group (ρ = -0.471, P = 0.011). The bone density of the regenerated bone increased after Gd exposure in the treated groups. The morphology of the regenerated bone from the treated groups became shorter and thicker. Our results showed that gadopentetate dimeglumine had osteogenic toxicity in zebrafish., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Differential diagnosis of essential tremor (ET) and Parkinson's disease (PD) can still be a challenge in clinical practice. These two tremor disorders may have different pathogenesis related to the substantia nigra (SN) and locus coeruleus (LC). Characterizing neuromelanin (NM) in these structures may help improve the differential diagnosis., Methods: Forty-three subjects with tremor-dominant PD (PD TD ), 31 subjects with ET, and 30 age- and sex-matched healthy controls were included. All subjects were scanned with NM magnetic resonance imaging (NM-MRI). NM volume and contrast measures for the SN and contrast for the LC were evaluated. Logistic regression was used to calculate predicted probabilities by using the combination of SN and LC NM measures. The discriminative power of the NM measures in detecting subjects with PD TD from ET was assessed with a receiver operative characteristic curve, and the area under the curve (AUC) was calculated., Results: The NM contrast-to-noise ratio (CNR) of the LC, the NM volume, and CNR of the SN on the right and left sides were significantly lower in PD TD subjects than in ET subjects or healthy controls (all P < 0.05). Furthermore, when combining the best model constructed from the NM measures, the AUC reached 0.92 in differentiating PD TD from ET., Conclusion: The NM volume and contrast measures of the SN and contrast for the LC provided a new perspective on the differential diagnosis of PD TD and ET, and the investigation of the underlying pathophysiology., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: Deep brain stimulation (DBS) has become a widely performed surgical procedure for patients with medically refractory movement disorders and mental disorders. It is clinically important to set up a MRI protocol to map the brain targets and electrodes of the patients before and after DBS and to understand the imaging artifacts caused by the electrodes., Methods: Five patients with DBS electrodes implanted in the habenula (Hb), fourteen patients with globus pallidus internus (GPi) targeted DBS, three pre-DBS patients and seven healthy controls were included in the study. The MRI protocol consisted of magnetization prepared rapid acquisition gradient echo T1 (MPRAGE T1W), 3D multi-echo gradient recalled echo (ME-GRE) and 2D fast spin echo T2 (FSE T2W) sequences to map the brain targets and electrodes of the patients. Phantom experiments were also run to determine both the artifacts and the susceptibility of the electrodes. Signal to noise ratio (SNR) on T1W, T2W and GRE datasets were measured. The visibility of the brain structures was scored according to the Rose criterion. A detailed analysis of the characteristics of the electrodes in all three sequence types was performed to confirm the reliability of the postoperative MRI approach. In order to understand the signal behavior, we also simulated the corresponding magnitude data using the same imaging parameters as in the phantom sequences., Results: The mean ± inter-subject variability of the SNRs, across the subjects for T1W, T2W, and GRE datasets were 20.1 ± 8.1, 14.9 ± 3.2, and 43.0 ± 7.6, respectively. High resolution MPRAGE T1W and FSE T2W data both showed excellent contrast for the habenula and were complementary to each other. The mean visibility of the habenula in the 25 cases for the MPRAGE T1W data was 5.28 ± 1.11; and the mean visibility in the 20 cases for the FSE T2W data was 5.78 ± 1.30. Quantitative susceptibility mapping (QSM), reconstructed from the ME-GRE sequence, provided sufficient contrast to distinguish the substructures of the globus pallidus. The susceptibilities of the GPi and globus pallidus externa (GPe) were 0.087 ± 0.013 ppm and 0.115 ± 0.015 ppm, respectively. FSE T2W sequences provided the best image quality with smallest image blooming of stimulator leads compared to MPRAGE T1W images and GRE sequence images, the measured diameters of electrodes were 1.91 ± 0.22, 2.77 ± 0.22, and 2.72 ± 0.20 mm, respectively. High resolution, high bandwidth and short TE (TE = 2.6 ms) GRE helped constrain the artifacts to the area of the electrodes and the dipole effect seen in the GRE filtered phase data provided an effective mean to locate the end of the DBS lead., Conclusion: The imaging protocol consisting of MPRAGE T1W, FSE T2W and ME-GRE sequences provided excellent pre- and post-operative visualization of the brain targets and electrodes for patients undergoing DBS treatment. Although the artifacts around the electrodes can be severe, sometimes these same artifacts can be useful in identifying their location., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Parkinson's disease (PD) is a clinically heterogeneous chronic progressive neuro-degenerative disease with loss of dopaminergic neurons in the nigrosome 1 (N1) territory of the substantia nigra pars compacta (SNpc). To date, there has been a major effort to identify changes in the N1 territory by monitoring increases of iron in the SNpc. However, there is no standard protocol being used to visualize or characterize the N1 territory. Therefore, the purpose of this study was to create a robust high quality, rapid imaging protocol, determine a slice by slice characterization of the appearance of N1 (the "N1 sign") and evaluate the loss of the N1 sign in order to differentiate healthy controls (HCs) from patients with PD. Firstly, one group of 10 HCs was used to determine the choice of imaging parameters. Secondly, another group of 80 HCs was used to characterize the appearance of the N1 sign and train the raters. In this step, the magnitude, susceptibility weighted images (SWI), quantitative susceptibility maps (QSM) and true SWI (tSWI) images were all reviewed using data from a 3D gradient recalled echo sequence. A resolution of 0.67 mm × 0.67 mm × 1.34 mm was chosen based on the ability to cover all the basal ganglia, midbrain and dentate nucleus with good signal-to-noise with echo times of 11 ms and 20 ms. Thirdly, 80 Parkinsonism and related disorders patients [idiopathic Parkinson's disease (IPD): 57; atypical parkinsonian syndromes (APs): 14; essential tremor (ET): 9] and one additional group of 80 age-matched HCs were blindly analyzed for the presence or absence of the N1 sign for a differential diagnosis. From the first group of 80 HCs, all of the 76 (100%) cases (4 were excluded due to motion artifacts) showed the N1 sign in one form or another after reviewing the first 5 caudal slices of the SN. For the second group of 80 HCs, 78 (97.5%) showed the N1 sign in at least 2 slices. Of the 80 Parkinsonism and related disorders patients, 32 (56.1%, 32/57) IPD and 6 (42.9%, 6/14) APs showed a bilateral loss of the N1 sign, 12 (21.1%, 12/57) IPD and 6 (42.9%, 6/14) APs showed the N1 sign unilaterally and 13 (22.8%, 13/57) IPD and 2 (14.2%, 2/14) APs showed the N1 sign bilaterally. Also, all 9 (100%, 9/9) ET patients showed the N1 sign bilaterally. The mean total structure and mean high susceptibility region for the SN for both IPD and APs patients with bilateral loss of N1 were higher than those of the HCs (p < 0.002). In conclusion, the N1 sign can be consistently visualized using tSWI with a resolution of at least 0.67 mm × 0.67 mm × 1.34 mm and can be seen in 95% of HCs., Competing Interests: Declaration of Competing Interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

The habenulae consist of a pair of small nuclei which bridge the limbic forebrain and midbrain monoaminergic centers. They are implicated in major depressive disorders due to abnormal phasic response when provoked by a conditioned stimulus. The lateral habenula (Lhb) is believed to be involved in dopamine metabolism and is now a target for deep brain stimulation, a treatment which has shown promising anti-depression effects. We imaged the habenulae with susceptibility weighted imaging (SWI) and quantitative susceptibility mapping (QSM) in order to localize the lateral habenula. Fifty-six healthy controls were recruited for this study. For the quantitative assessment, we traced the structure to compute volume from magnitude images and mean susceptibility bilaterally for the habenula on QSM. Thresholding methods were used to delineate the Lhb habenula on QSM. SWI, true SWI (tSWI), and QSM data were subjectively reviewed for increased Lhb contrast. SWI, QSM, and tSWI showed bilateral signal changes in the posterior location of the habenulae relative to the anterior location, which may indicate increased putative iron content within the Lhb. This signal behavior was shown in 41/44 (93%) subjects. In summary, it is possible to localize the lateral component of the habenula using SWI and QSM at 3 T., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: To date there are no validated MRI biomarkers to assist diagnosis of Parkinson's disease (PD). Our aim was to investigate PD related iron changes in the substantia nigra pars compacta (SNpc) as defined by neuromelanin-sensitive MR contrast., Methods: Thirty-nine PD participants and 33 healthy controls were scanned at 3.0-T using a 16-echo gradient echo sequence to create R 2 * maps for the evaluation of iron content to find the overlap with a neuromelanin based SNpc mask. The SNpc overlap percentage with the R 2 * map, and the R 2 * values in both the whole SNpc and the overlap volume were compared between PD and control groups, and correlated with clinical features for PD participants. Finally, the diagnostic performance of the SNpc overlap percentage was evaluated using ROC analysis., Results: PD related iron changes mostly occur in the lateral-ventral part of the neuromelanin SNpc. The R 2 * values in the whole SNpc and the SNpc overlap volume, and the SNpc overlap percentage were larger in PD participants than in controls. Furthermore, the SNpc overlap percentage was positively correlated with the disease duration in PD. The SNpc overlap percentage provided excellent diagnostic accuracy for discriminating PD participants from controls (AUC = 0.93), while the R 2 * values in the whole SNpc or the overlap volume were less effective., Conclusion: The overlap between the iron content as determined by R 2 * mapping and neuromelanin in the substantia nigra pars compacta has the potential to be a neuroimaging biomarker for diagnosing Parkinson's disease., (Copyright © 2020. Published by Elsevier Inc.)

One major thrust in radiology today is image standardization with a focus on rapidly acquired quantitative multi-contrast information. This is critical for multi-center trials, for the collection of big data and for the use of artificial intelligence in evaluating the data. Strategically acquired gradient echo (STAGE) imaging is one such method that can provide 8 qualitative and 7 quantitative pieces of information in 5 min or less at 3 T. STAGE provides qualitative images in the form of proton density weighted images, T1 weighted images, T2* weighted images and simulated double inversion recovery (DIR) images. STAGE also provides quantitative data in the form of proton spin density, T1, T2* and susceptibility maps as well as segmentation of white matter, gray matter and cerebrospinal fluid. STAGE uses vendors' product gradient echo sequences. It can be applied from 0.35 T to 7 T across all manufacturers producing similar results in contrast and quantification of the data. In this paper, we discuss the strengths and weaknesses of STAGE, demonstrate its contrast-to-noise (CNR) behavior relative to a large clinical data set and introduce a few new image contrasts derived from STAGE, including DIR images and a new concept referred to as true susceptibility weighted imaging (tSWI) linked to fluid attenuated inversion recovery (FLAIR) or tSWI-FLAIR for the evaluation of multiple sclerosis lesions. The robustness of STAGE T1 mapping was tested using the NIST/NIH phantom, while the reproducibility was tested by scanning a given individual ten times in one session and the same subject scanned once a week over a 12-week period. Assessment of the CNR for the enhanced T1W image (T1WE) showed a significantly better contrast between gray matter and white matter than conventional T1W images in both patients with Parkinson's disease and healthy controls. We also present some clinical cases using STAGE imaging in patients with stroke, metastasis, multiple sclerosis and a fetus with ventriculomegaly. Overall, STAGE is a comprehensive protocol that provides the clinician with numerous qualitative and quantitative images., (Published by Elsevier Inc.)

Parkinson's disease is the second most common neurodegenerative disease in the elderly after Alzheimer's disease. The aetiology and pathogenesis of Parkinson's disease (PD) are still unclear, but the loss of dopaminergic cells and the excessive iron deposition in the substantia nigra (SN) are associated with the pathophysiology. As an imaging technique that can quantitatively reflect the amount of iron deposition, Quantitative Susceptibility Mapping (QSM) has been shown to be a promising modality for the diagnosis of PD. In the present work, we propose a hybrid feature extraction method for PD diagnosis using QSM images. First, we extract radiomics features from the SN using QSM and employ machine learning algorithms to classify PD and normal controls (NC). This approach allows us to investigate which features are most vulnerable to the effects of the disease. Along with this approach, we propose a Convolutional Neural Network (CNN) based method which can extract different features from the QSM image to further support the diagnosis of PD. Finally, we combine these two types of features and we find that the radiomics features and CNN features are complementary to each other, which helps further improve the classification (diagnostic) performance. We conclude that: (1) radiomics features from QSM data have significant clinical value for the diagnosis of PD; (2) CNN features are also useful in the diagnosis of PD; and (3) the combination of radiomics features and CNN features can enhance the diagnostic accuracy., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)