Transverse Relaxation Anisotropy of the Achilles and Patellar Tendon Studied by MR Microscopy.

BACKGROUND: T2 * anisotropy affects the clinical assessment of tendons (magic-angle artifact) and may be a source of T2 *-misinterpretation. PURPOSE: To analyze T2 *-anisotropy and T2 *-decay of Achilles and patellar tendons in vitro at microscopic resolution using a variable-echo-time (vTE) sequence. STUDY TYPE: Prospective. SPECIMEN: Four human Achilles and four patellar tendons. FIELD STRENGTH/SEQUENCE: A 7 T MR-microscopy; 3D-vTE spoiled-gradient-echo-sequence (T2 *-mapping). ASSESSMENT: All tendons were measured at 0° and 55° relative to B0 . Additional angles were measured for one Achilles and one patellar tendon for a total of 11 angles ranging from 0° to 90°. T2 *-decay was analyzed with mono- and bi-exponential signal fitting. Mono-exponential T2 *-values (T2 *m ), short and long T2 *-components (T2 *s , T2 *l ), and the fraction of the short component Fs of the bi-exponential T2 *-fit were calculated. T2 *-decay characteristics were compared with morphological MRI and histologic findings based on a region-of-interest analysis. STATISTICAL TESTS: Akaike information criterion (AICC ), F-test, and paired t-test. A P value smaller than the α-level of 0.05 was considered statistically significant. RESULTS: T2 *m -values between fiber-to-field angles of 0° and 55° were increased on average from T2 *m (0°) = 1.92 msec to T2 *m (55°) = 29.86 msec (15.5-fold) in the Achilles and T2 *m (0°) = 1.46 msec to T2 *m (55°) = 23.33 msec (16.0-fold) in the patellar tendons. The changes in T2 *m -values were statistically significant. For the whole tendon, according to F-test and AICC , a bi-exponential model was preferred for angles close to 0°, while the mono-exponential model tended to be preferred at angles close to 55°. CONCLUSION: MR-microscopy provides a deeper insight into the relationship between T2 *-decay (mono- vs. bi-exponential model) and tendon heterogeneity. Changes in fiber-to-field angle result in significant changes in T2 *-values. Thus, we conclude that awareness of T2 *-anisotropy should be noted in quantitative T2 *-mapping of tendons to avoid T2 *-misinterpretation such as a false positive detection of degeneration due to large fiber-to-field angles. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

Chondral and Osteochondral Femoral Cartilage Lesions Treated with GelrinC: Significant Improvement of Radiological Outcome Over Time and Zonal Variation of the Repair Tissue Based on T2 Mapping at 24 Months.

OBJECTIVE: To prospectively assess the efficacy of GelrinC in the treatment of chondral and osteochondral femoral cartilage lesions using morphological (Magnetic Resonance Observation of Cartilage Repair Tissue [MOCART]) and quantitative (T2-mapping) magnetic resonance imaging (MRI). DESIGN: This study was designed as a prospective single-arm, open label, multicenter study. Morphological magnetic resonance imaging (MRI) for MOCART assessment and T2 mapping was performed 1 week and 6, 12, 18, and 24 months after GelrinC implantation. Evaluation of T2 mapping was based on the assessment of global T2 indices (T2 of the repair tissue [RT] divided by T2 of healthy reference cartilage) and zonal variation. RESULTS: Fifty-six (20 female) patients were prospectively enrolled. The mean MOCART score significantly increased from baseline to the 24-month follow-up with 88.8 (95% CI, 85.8-91.9; P < 0.001) for all lesions combined as well as 86.8 (95% CI, 83.0-90.6) for chondral lesions and 94.1 (95% CI, 68.55-100) for osteochondral lesions. Furthermore, based on T2 mapping, significant zonal variation of the RT was observed at 24 months (P = 0.039), which did not differ significantly from healthy reference cartilage (P = 0.6). CONCLUSION: Increasing MOCART scores were observed throughout the follow-up period, indicative of maturation of the cartilage repair. Significant zonal variation of the RT at 24 months might indicate the transformation into hyaline cartilage-like RT. Slightly differing morphological outcome between chondral and osteochondral lesions, but similar global and zonal T2 indices at 24 months, support the potential of GelrinC as a treatment option for both lesion types.

Contribution of macromolecules to brain 1 H MR spectra: Experts' consensus recommendations.

Proton MR spectra of the brain, especially those measured at short and intermediate echo times, contain signals from mobile macromolecules (MM). A description of the main MM is provided in this consensus paper. These broad peaks of MM underlie the narrower peaks of metabolites and often complicate their quantification but they also may have potential importance as biomarkers in specific diseases. Thus, separation of broad MM signals from low molecular weight metabolites enables accurate determination of metabolite concentrations and is of primary interest in many studies. Other studies attempt to understand the origin of the MM spectrum, to decompose it into individual spectral regions or peaks and to use the components of the MM spectrum as markers of various physiological or pathological conditions in biomedical research or clinical practice. The aim of this consensus paper is to provide an overview and some recommendations on how to handle the MM signals in different types of studies together with a list of open issues in the field, which are all summarized at the end of the paper.

Assessment of Low-Grade Focal Cartilage Lesions in the Knee With Sodium MRI at 7 T: Reproducibility and Short-Term, 6-Month Follow-up Data.

OBJECTIVES: Several articles have investigated potential of sodium (Na) magnetic resonance imaging (MRI) for the in vivo evaluation of cartilage health, but so far no study tested its feasibility for the evaluation of focal cartilage lesions of grade 1 or 2 as defined by the International Cartilage Repair Society. The aims of this study were to evaluate the ability of Na-MRI to differentiate between early focal lesions and normal-appearing cartilage, to evaluate within-subject reproducibility of Na-MRI, and to monitor longitudinal changes in participants with low-grade, focal chondral lesions. MATERIALS AND METHODS: Thirteen participants (mean age, 50.1 ± 10.9 years; 7 women, 6 men) with low-grade, focal cartilage lesions in the weight-bearing region of femoral cartilage were included in this prospective cohort study. Participants were assessed at baseline, 1 week, 3 months, and 6 months using morphological MRI at 3 T and 7 T, compositional Na-MRI at 7 T, and the Knee Injury and Osteoarthritis Outcome Score (KOOS) questionnaire. Na signal intensities corrected for coil sensitivity and partial volume effect (Na-cSI) were calculated in the lesion, and in weight-bearing and non-weight-bearing regions of healthy femoral cartilage. Coefficients of variation, repeated measures analysis of covariance models, and Pearson correlation coefficients were calculated to evaluate within-subject reproducibility as well as cross-sectional and longitudinal changes in Na-cSI values. RESULTS: The mean coefficients of variation of Na-cSI values between the baseline and 1-week follow-up were 5.1% or less in all cartilage regions. Significantly lower Na-cSI values were observed in lesion than in weight-bearing and non-weight-bearing regions at all time points (all P values ≤ 0.002). Although a significant decrease from baseline Na-cSI values in lesion was found at 3-month visit (P = 0.015), no substantial change was observed at 6 months. KOOS scores have improved in all subscales at 3 months and 6 months visit, with a significant increase observed only in the quality of life subscale (P = 0.004). CONCLUSIONS: In vivo Na-MRI is a robust and reproducible method that allows to differentiate between low-grade, focal cartilage lesions and normal-appearing articular cartilage, which supports the concept that compositional cartilage changes can be found early, before the development of advanced morphological changes visible at clinical 3-T MRI.

Advanced single voxel 1 H magnetic resonance spectroscopy techniques in humans: Experts' consensus recommendations.

Conventional proton MRS has been successfully utilized to noninvasively assess tissue biochemistry in conditions that result in large changes in metabolite levels. For more challenging applications, namely, in conditions which result in subtle metabolite changes, the limitations of vendor-provided MRS protocols are increasingly recognized, especially when used at high fields (≥3 T) where chemical shift displacement errors, B0 and B1 inhomogeneities and limitations in the transmit B1 field become prominent. To overcome the limitations of conventional MRS protocols at 3 and 7 T, the use of advanced MRS methodology, including pulse sequences and adjustment procedures, is recommended. Specifically, the semiadiabatic LASER sequence is recommended when TE values of 25-30 ms are acceptable, and the semiadiabatic SPECIAL sequence is suggested as an alternative when shorter TE values are critical. The magnetic field B0 homogeneity should be optimized and RF pulses should be calibrated for each voxel. Unsuppressed water signal should be acquired for eddy current correction and preferably also for metabolite quantification. Metabolite and water data should be saved in single shots to facilitate phase and frequency alignment and to exclude motion-corrupted shots. Final averaged spectra should be evaluated for SNR, linewidth, water suppression efficiency and the presence of unwanted coherences. Spectra that do not fit predefined quality criteria should be excluded from further analysis. Commercially available tools to acquire all data in consistent anatomical locations are recommended for voxel prescriptions, in particular in longitudinal studies. To enable the larger MRS community to take advantage of these advanced methods, a list of resources for these advanced protocols on the major clinical platforms is provided. Finally, a set of recommendations are provided for vendors to enable development of advanced MRS on standard platforms, including implementation of advanced localization sequences, tools for quality assurance on the scanner, and tools for prospective volume tracking and dynamic linear shim corrections.

Magnetic resonance spectroscopy in the rodent brain: Experts' consensus recommendations.

In vivo MRS is a non-invasive measurement technique used not only in humans, but also in animal models using high-field magnets. MRS enables the measurement of metabolite concentrations as well as metabolic rates and their modifications in healthy animals and disease models. Such data open the way to a deeper understanding of the underlying biochemistry, related disturbances and mechanisms taking place during or prior to symptoms and tissue changes. In this work, we focus on the main preclinical 1H, 31P and 13C MRS approaches to study brain metabolism in rodent models, with the aim of providing general experts' consensus recommendations (animal models, anesthesia, data acquisition protocols). An overview of the main practical differences in preclinical compared with clinical MRS studies is presented, as well as the additional biochemical information that can be obtained in animal models in terms of metabolite concentrations and metabolic flux measurements. The properties of high-field preclinical MRS and the technical limitations are also described.

Improved off-resonance phase behavior using a phase-inverted adiabatic half-passage pulse for 13 C MRS in humans at 7 T.

In vivo 13 C MRS at high field benefits from an improved SNR and spectral resolution especially when using surface coils in combination with adiabatic pulses, such as the adiabatic half-passage (AHP) pulse for 13 C excitation. However, the excitation profile of the AHP pulse is asymmetric relative to the carrier frequency, which could lead to asymmetric excitation of the spectral lines relative to the center of the spectrum. In this study, a pulse-acquire sequence was designed for adiabatic 13 C excitation with a symmetric bandwidth, utilizing a combination of two AHP pulses with inverted phases in alternate scans. Magnetization and phase behavior as a function of frequency offset and RF amplitude of the B1 field, as well as the steady-state transverse magnetization response to off-resonance, were simulated. Excitation properties of the combined pulse sequence were studied by 23 Na imaging and 13 C spectroscopy in vitro on a phantom and in vivo on the human calf at 7 T. Simulations demonstrated symmetric transverse magnetization and phase with respect to positive and negative frequency offsets when using two AHP pulses with inverted phases in alternate scans, thereby minimizing baseline distortion and achieving symmetric T1 weighting, as confirmed by in vitro measurements. The intensities of the lipid peaks at 15, 30, 62, 73, and 130 ppm were in agreement with those theoretically predicted using two AHP pulses with inverted phases in alternate scans. We conclude that using two phase-inverted AHP pulses improves the symmetry of the 13 C excitation profile and phase response to off-resonance effects at 7 T in comparison with using a single AHP pulse.

Magnetic Resonance Imaging of the Musculoskeletal System at 7T: Morphological Imaging and Beyond.

In 2017, a whole-body 7T magnetic resonance imaging (MRI) device was given regulatory approval for clinical use in both the EU and United States for neuro and musculoskeletal applications. As 7 Tesla allows for higher signal-to-noise , which results in higher resolution images than those obtained on lower-field-strength scanners, it has attracted considerable attention from the musculoskeletal field, as evidenced by the increasing number of publications in the last decade. Besides morphological imaging, the quantitative MR methods, such as T2, T2*, T1ρ mapping, sodium imaging, chemical-exchange saturation transfer, and spectroscopy, substantially benefit from ultrahigh field scanning. In this review, we provide technical considerations for the individual techniques and an overview of (mostly) clinical applications for the assessment of cartilage, tendon, meniscus, and muscle. The first part of the review is dedicated to morphological applications at 7T, and the second part describes the most recent developments in quantitative MRI at 7T.

7T CEST MRI: A potential imaging tool for the assessment of tumor grade and cell proliferation in breast cancer.

OBJECTIVES: To investigate the feasibility of chemical exchange saturation transfer (CEST) MRI in patients with breast carcinomas and possible correlations between magnetization transfer asymmetry (MTRasym) values and histological features, such as tumor grade and the Ki-67 proliferation index. MATERIALS AND METHODS: Nine healthy subjects and 18 female patients were enrolled for this study. The imaging protocol for the patients consisted of diffusion-weighted imaging (DWI), CEST imaging, and T1-weighted, contrast-enhanced (CE)-MRI. CEST was performed using a 3D gradient echo (GRE) sequence, employing eight pre-saturation pulses of a duration of 50 ms and a duty cycle (DC) of 80%, with a mean amplitude of the saturation pulse train of 1 µT. The Z-spectrum was plotted and MTRasym values calculated for the frequency of the maximum of MTRasym curve, were correlated with the Ki-67 proliferation index and apparent diffusion coefficient (ADC). Patient data were statistically assessed using the Games-Howell post-hoc and Pearson's correlation test. RESULTS: Different tumor types had asymmetry peaks at different positions of Z-spectrum. MTRasym (mean ±â€¯SD) (%) calculated for G1 (3.0 ±â€¯0.3; range: 2.70-3.50) was not significantly lower than for G2 (4.50 ±â€¯1.30; range: 3.20-6.50; p = 0.066). In contrast, the increase in MTRasym between G1 and G3 (6.40 ±â€¯1.70; range: 4.80-9.80) lesions was significant (p = 0.007). No significant difference was observed between G2 and G3 with regard to MTRasym (p = 0.089). There was a strong positive correlation between the MTRasym, and Ki-67 proliferation index (r = 0.890; p = 0.001), while there was a moderate negative correlation between MTRasym and ADC values (r = -0.506; p = 0.027). CONCLUSIONS: Calculated MTRasym demonstrates a strong positive correlation with tumor proliferation and has the potential to become a valuable biomarker for breast tumor characterization.

The comparison of the performance of 3 T and 7 T T2 mapping for untreated low-grade cartilage lesions.

OBJECTIVE: To investigate T2 mapping as a possible marker for low-grade human articular cartilage lesions during a one-year follow-up, possible changes during the follow-up and compare the reliability and sensitivity of these measurements on high-field (3 T) and ultra-high-field (7 T) MRI scanners. DESIGN: Twenty-one patients with femoral, tibial and patellar cartilage defect in the knee joint participated in the study. The MRI protocol consisted of morphological, as well as three-dimensional triple-echo steady-state (3D-TESS) T2 mapping sequences with similar parameters at 3T and 7T. Patients were scanned at five time-points up to 12 months. T2 values were evaluated in the lesion and healthy-appearing regions for superficial and deep cartilage zone. The repeated ANOVA was used to determine differences in T2 values at various time points. RESULTS: A significant decrease in T2 values was observed between baseline and six months in the superficial layer of the lesion in patients at 3 T (decrease from 41.89 ±â€¯9.3 ms to 31.21 ±â€¯7.2 ms, which is a difference of -5.67 ±â€¯2.2 ms (p = 0.031)), and at 12 months in the superficial layer of the lesion in patients at 3 T (decrease from 41.89 ±â€¯9.3 ms to 35.28 ±â€¯4.9 ms, which is a difference of -6.60 ±â€¯4.4 ms (p = 0.044). No significant differences were recorded at 7 T. CONCLUSION: The change in T2 values acquired with 3 T 3D-TESS appears to be reflecting subtle changes of cartilage composition in the course of low-grade lesion development. 7 T T2 mapping does not reflect these changes probably due to completely decayed short T2 component.

Introduction to nuclear magnetic resonance.

Nuclear magnetic resonance spectroscopy is a useful tool for studying normal and pathological biochemical processes in tissues. In this review, the principles of nuclear magnetic resonance and methods of obtaining nuclear magnetic resonance spectra are briefly outlined. The origin of the most important spectroscopic parameters-chemical shifts, coupling constants, longitudinal and transverse relaxation times, and spectroscopic line intensities-is explained, and the role of these parameters in interpretation of spectra is addressed. Basic methodological concepts of localized spectroscopy and spectroscopic imaging for the study of tissue metabolism in vivo are also described.

New Technology in Imaging Cartilage of the Ankle.

The incidence of osteochondral lesions, as well as osteoarthritis of the ankle joint following osteochondritis dissecans and trauma, has been reappraised in recent years. Consequently, an increasing number of surgical interventions using different cartilage repair techniques is performed in the ankle joint, which has resulted in a growing demand for repetitive and objective assessment of cartilage tissue and its repair. While morphological imaging does enable monitoring of macroscopic changes with increasing precision, it fails to provide information about the ultrastructural composition of cartilage. The significance of molecular changes in cartilage matrix composition, however, is increasingly recognized, as it is assumed that macroscopic cartilage degeneration is preceded by a loss in glycosaminoglycans and a disorganization of the collagen network. Recent advances in biochemical magnetic resonance imaging (MRI) have yielded sequences sensitive to these changes, thus providing invaluable insight into both early cartilage degeneration and maturation of repair tissue, on a molecular level. The aim of this review was to provide a comprehensive overview of these techniques, including water and collagen-sensitive T2/T2* mapping, as well as glycosaminoglycan-sensitive sequences such as delayed gadolinium-enhanced MRI of cartilage dGEMRIC, and sodium imaging, and describe their applications for the ankle joint.

Metabolic Study of Breast MCF-7 Tumor Spheroids after Gamma Irradiation by (1)H NMR Spectroscopy and Microimaging.

Multicellular tumor spheroids are an important model system to investigate the response of tumor cells to radio- and chemotherapy. They share more properties with the original tumor than cells cultured as 2D monolayers do, which helps distinguish the intrinsic properties of monolayer cells from those induced during cell aggregation in 3D spheroids. The paper investigates some metabolic aspects of small tumor spheroids of breast cancer and their originating MCF-7 cells, grown as monolayer, by means of high-resolution (HR) (1)H NMR spectroscopy and MR microimaging before and after gamma irradiation. The spectra of spheroids were characterized by higher intensity of mobile lipids, mostly neutral lipids, and glutamine (Gln) signals with respect to their monolayer cells counterpart, mainly owing to the lower oxygen supply in spheroids. Morphological changes of small spheroids after gamma-ray irradiation, such as loss of their regular shape, were observed by MR microimaging. Lipid signal intensity increased after irradiation, as evidenced in both MR localized spectra of the single spheroid and in HR NMR spectra of spheroid suspensions. Furthermore, the intense Gln signal from spectra of irradiated spheroids remained unchanged, while the low Gln signal observed in monolayer cells increased after irradiation. Similar results were observed in cells grown in hypoxic conditions. The different behavior of Gln in 2D monolayers and in 3D spheroids supports the hypothesis that a lower oxygen supply induces both an upregulation of Gln synthetase and a downregulation of glutaminases with the consequent increase in Gln content, as already observed under hypoxic conditions. The data herein indicate that (1)H NMR spectroscopy can be a useful tool for monitoring cell response to different constraints. The use of spheroid suspensions seems to be a feasible alternative to localized spectroscopy since similar effects were found after radiation treatment.

Quantitative evaluation of cerebral white matter in patients with multiple sclerosis using multicomponent T2 mapping.

OBJECTS: A standard magnetic resonance imaging (MRI) investigation of white matter (WM) areas with visible or expected pathology does not explain satisfactorily the relation between pathology and clinical outcome. Therefore, we focused on multicomponent T2 mapping of WM with the intention to characterize the WM, including normal-appearing white matter that has normal and prolonged T2 and lesions, including degenerated tissue. MATERIALS AND METHODS: Twenty-nine patients with clinically diagnosed MS and 27 healthy controls underwent MRI examination. T2 mapping of the WM across the two whole MRI slices was carried out. The relative abundance of biologically relevant T2 regions was correlated with age and the expanded disability status scale (EDSS). RESULTS: The relative abundance of the T2 values of water trapped in myelin increased with age in both healthy subjects (p < 0.05) and MS patients (p < 0.05). The relative abundance of intermediate T2 assigned to intra- and extracellular water decreased with age in both groups (p < 0.05) and with EDSS (p < 0.005) in the MS patients. The mixed water pools with a T2 above 110 ms were not related to age, but strongly increased with EDSS (p < 0.000005). CONCLUSION: Our results suggest that multicomponent T2 mapping of the WM can be a useful parameter for monitoring the progression of MS in patients.

Reproducibility and regional variations of an improved gagCEST protocol for the in vivo evaluation of knee cartilage at 7 T.

OBJECTIVE: The objective was to establish a gagCEST protocol that would enable robust and reproducible assessment of the glycosaminoglycan (GAG) content in knee cartilage at 7 T within a clinically feasible measurement time. MATERIALS AND METHODS: Ten young healthy volunteers (mean age 26 years, range 24-28, five males, five females) were examined on a 7 T MR system. Informed consent was obtained from all individual participants prior to enrollment into the study. Each volunteer was measured twice for reproducibility assessment. The examined knee was immobilized using a custom-made fixation device. For the gagCEST measurement, a prototype segmented 3-D RF-spoiled gradient-echo sequence with an improved saturation scheme employing adiabatic pulses was used in a scan time of 19 min. The asymmetry of the Z-spectra (MTRasym) in selected regions of interest in knee cartilage was calculated. Differences in MTRasym between different regions were evaluated using ANOVA and the Bonferroni corrected post hoc test. RESULTS: The improvement of the saturation scheme reduced the influence of field inhomogeneities, resulted in more uniform saturation, and allowed for good reproducibility in a reasonable measurement time (19 min), as demonstrated by an intraclass correlation coefficient of 0.77. Improved fixation helped to reduce motion artifacts. Whereas similar MTRasym values were found for weight-bearing and non-weight-bearing femoral cartilage, lower values were observed in the trochlear groove (p = 0.028), patellar (p = 0.015) and tibial cartilage (p < 0.001) when compared to non-weight-bearing femoral cartilage. CONCLUSION: Reasonable reproducibility and sensitivity to regional differences in GAG content suggests that the improved gagCEST protocol might be useful for assessing the biochemical changes in articular cartilage that are associated with early stages of cartilage degeneration.

The compositional difference between ankle and knee cartilage demonstrated by T2 mapping at 7 Tesla MR.

OBJECTIVES: The aim was to systematically compare T2 relaxation times of the knee and ankle cartilage within subjects at 7T. METHODS: Ten healthy volunteers were examined by 7 Tesla MR using a three-dimensional triple-echo steady state sequence (3D-TESS). The differences between seven cartilage compartments (patella, femur, proximal tibia, and distal tibia and talus in both medial and lateral facet) were analyzed by ANOVA. RESULTS: The results showed statistically significantly higher T2 (mean ± standard deviation, in milliseconds) values in patellar (25.8 ± 1.2) and femoral (24.9 ± 1.3) cartilage compared to the tibial (19.2 ± 1) and talar (18.1 ± 0.6 ms) cartilage. The cartilages of the medial and lateral facet in the ankle joint were not significantly different (p>0.05). CONCLUSIONS: This is the first study to systematically compare within-subject T2 values in the knee and ankle non-invasively, in vivo. Our results are in agreement with the previous findings demonstrating different biochemical and biomechanical properties between the knee and ankle cartilage.

Assessment of brain metabolite correlates of adeno-associated virus-mediated over-expression of human alpha-synuclein in cortical neurons by in vivo (1) H-MR spectroscopy at 9.4 T.

In this study, we used proton-localized spectroscopy ((1) H-MRS) for the acquisition of the neurochemical profile longitudinally in a novel rat model of human wild-type alpha-synuclein (α-syn) over-expression. Our goal was to find out if the increased α-syn load in this model could be linked to changes in metabolites in the frontal cortex. Animals injected with AAV vectors encoding for human α-syn formed the experimental group, whereas green fluorescent protein expressing animals were used as the vector-treated control group and a third group of uninjected animals were used as naïve controls. Data were acquired at 2, 4, and 8 month time points. Nineteen metabolites were quantified in the MR spectra using LCModel software. On the basis of 92 spectra, we evaluated any potential gender effect and found that lactate (Lac) levels were lower in males compared to females, while the opposite was observed for ascorbate (Asc). Next, we assessed the effect of age and found increased levels of GABA, Tau, and GPC+PCho. Finally, we analyzed the effect of treatment and found that Lac levels (p = 0.005) were specifically lower in the α-syn group compared to the green fluorescent protein and control groups. In addition, Asc levels (p = 0.05) were increased in the vector-injected groups, whereas glucose levels remained unchanged. This study indicates that the metabolic switch between glucose-lactate could be detectable in vivo and might be modulated by Asc. No concomitant changes were found in markers of neuronal integrity (e.g., N-acetylaspartate) consistent with the fact that α-syn over-expression in cortical neurons did not result in neurodegeneration in this model. We acquired the neurochemical profile longitudinally in a rat model of human wild-type alpha-synuclein (α-syn) over-expression in cortical neurons. We found that Lactate levels were reduced in the α-syn group compared to the control groups and Ascorbate levels were increased in the vector-injected groups. No changes were found in markers of neuronal integrity consistent with the fact that α-syn over-expression did not result in frank neurodegeneration.