Dynamics of Nigral Iron Accumulation in Parkinson's Disease: From Diagnosis to Late Stage.

BACKGROUND: Higher nigral iron has been reported in Parkinson's disease (PD). OBJECTIVE: The aim is to understand the dynamics of nigral iron accumulation in PD and its association with drug treatment. METHODS: Susceptibility magnetic resonance imaging data were obtained from 79 controls and 18 drug-naive (PDDN ) and 87 drug-treated (PDDT ) PD patients. Regional brain iron in basal ganglia and cerebellar structures was estimated using quantitative susceptibility mapping. Nigral iron was compared between PDDN and PDDT subgroups defined by disease duration (early [PDE, <2 years], middle [PDM, 2-6 years], and later [PDL, >6 years]). Associations with both disease duration and types of antiparkinson drugs were explored using regression analysis. RESULTS: Compared to controls, PDDN had lower iron in the substantia nigra (P = 0.018), caudate nucleus (P = 0.038), and globus pallidus (P = 0.01) but not in the putamen or red nucleus. In contrast, PDDT had higher iron in the nigra (P < 0.001) but not in other regions, compared to either controls or PDDN . Iron in the nigra increased with disease duration (PDE > PDDN [P = 0.001], PDM > PDE [P = 0.045]) except for PDM versus PDL (P = 0.226). Levodopa usage was associated with higher (P = 0.013) nigral iron, whereas lower nigral iron was correlated with selegiline usage (P = 0.030). CONCLUSION: Nigral iron is lower before the start of dopaminergic medication and then increases throughout the disease until it plateaus at late stages, suggesting increased iron may not be an etiological factor. Interestingly, PD medications may have differential associations with iron accumulation that need further investigation. © 2022 International Parkinson and Movement Disorder Society.

An Electronic Aerosol Delivery System for Functional Magnetic Resonance Imaging.

BACKGROUND: Public health concerns over the addictive potential of electronic cigarettes (e-cigs) have heightened in recent years. Brain function during e-cig use could provide an objective measure of the addictive potential of new vaping products to facilitate research; however, there are limited methods for delivering e-cig aerosols during functional magnetic resonance imaging (fMRI). The current study describes the development and feasibility testing of a prototype to deliver up to four different e-cig aerosols during fMRI. METHODS: Standardized methods were used to test the devices' air flow variability, nicotine yield, and free radical production. MRI scans were run with and without the device present to assess its safety and effects on MRI data quality. Five daily smokers were recruited to assess plasma nicotine absorption from e-liquids containing nicotine concentrations of 8, 11, 16, 24, and 36 mg/ml. Feedback was collected from participants through a semi-structured interview and computerized questionnaire to assess comfort and subjective experiences of inhaling aerosol from the device. RESULTS: Nicotine yield captured from the aerosol produced by the device was highly correlated with the nicotine concentration of the e-liquids used (R2 = 0.965). Nicotine yield was reduced by a mean of 48% and free radical production by 17% after traveling through the device. The e-liquid containing the highest nicotine concentration tested (36 mg/ml) resulted in the highest plasma nicotine boost (6.6 ng/ml). Overall, participants reported that the device was comfortable to use and inhaling the e-cig aerosols was tolerable. The device was determined to be safe for use during fMRI and had insignificant effects on scan quality. CONCLUSIONS: With the current project, we were able to design a working prototype that safely and effectively delivers e-cig aerosols during fMRI. The device has the potential to be used to assess brain activation during e-cig use and to compare brain reactivity to varying flavors, nicotine concentrations, and other e-cig characteristics.

The exercise pressor reflex and active O2 transport in peripheral arterial disease.

It is unclear if the exaggerated exercise pressor reflex observed in peripheral arterial disease (PAD) patients facilitates Oxygen (O2 ) transport during presymptomatic exercise. Accordingly, this study compared O2 transport between PAD patients and healthy controls during graded presymptomatic work. Seven PAD patients and seven healthy controls performed dynamic plantar flexion in the bore of a 3T MRI scanner. Perfusion, T2 * (an index of relative tissue oxygenation), and SvO2 (a measure of venous oxygen saturation) were collected from the medial gastrocnemius (MG) during the final 10 seconds of each stage. Blood pressure was also collected during the final minute of each stage. As expected, the pressor response to presymptomatic work (4 kg) was exaggerated in PAD patients compared to controls (+14 mmHg ± 4 and +7 mmHg ± 2, P ≤ 0.034). When normalized to changes in free water content (S0 ), T2 * was lower at 2 kg in PAD patients compared to controls (-0.91 Δms/ΔAU ± 0.3 and 0.57 Δms/ΔAU ± 0.3, P ≤ 0.008); followed by a greater increase in perfusion at 4 kg in the PAD group (+18.8 mL/min/100g ± 6.2 vs. -0.21 mL/min/100g ± 3.2 in PAD and controls, P ≤ 0.026). Lastly, SvO2 decreased at 4 kg in both groups (-13% ± 4 and -2% ± 4 in PAD and controls, P ≤ 0.049), suggesting an increase in O2 extraction in the PAD group. Based on these findings, O2 transport appears to be augmented during graded presymptomatic work in PAD patients, and this may be partially mediated by an exaggerated pressor response.

Bloch-based MRI system simulator considering realistic electromagnetic fields for calculation of signal, noise, and specific absorption rate.

PURPOSE: To describe and introduce new software capable of accurately simulating MR signal, noise, and specific absorption rate (SAR) given arbitrary sample, sequence, static magnetic field distribution, and radiofrequency magnetic and electric field distributions for each transmit and receive coil. THEORY AND METHODS: Using fundamental equations for nuclear precession and relaxation, signal reception, noise reception, and calculation of SAR, a versatile MR simulator was developed. The resulting simulator was tested with simulation of a variety of sequences demonstrating several common imaging contrast types and artifacts. The simulation of intravoxel dephasing and rephasing with both tracking of the first order derivatives of each magnetization vector and multiple magnetization vectors was examined to ensure adequate representation of the MR signal. A quantitative comparison of simulated and experimentally measured SNR was also performed. RESULTS: The simulator showed good agreement with our expectations, theory, and experiment. CONCLUSION: With careful design, an MR simulator producing realistic signal, noise, and SAR for arbitrary sample, sequence, and fields has been created. It is hoped that this tool will be valuable in a wide variety of applications.