Purpose: To introduce and evaluate a method of prospective motion correction for localized proton magnetic resonance spectroscopy (1H-MRS) using a single-camera optical tracking system. Materials and Methods:Five healthy participants were scanned at 3T using a point-resolved spectroscopic sequence (PRESS) with a motion-tracking module and phase navigator. Head motion in six degrees was tracked with a Retro-Grate Reflector (RGR) tracking system and target via a mirror mounted inside the bore. Participants performed a series of three predetermined motion patterns during scanning.Results: Left-right rotation (Rz) (average 12 ) resulted in an increase in the total choline to total creatine ratio (Cho/Cr) of þ14.6 6 1.5% (P ¼ 0.0009) for scans without correction, but no change for scans with correction (þ1.1 6 1.5%; P ¼ 0.76). Spectra with uncorrected Z-translations showed large lipid peaks (skull) with changes in Cho/Cr of À13.2 6 1.6% (P ¼ 0.02, no motion correction) and À2.2 6 2.4% (P ¼ 0.51) with correction enabled. There were no significant changes in the ratios of N-acetylaspartate, glutamateþglutamine, or myo-inositol to creatine compared to baseline scans for all experiments.Conclusion: Prospective motion correction for 1H-MRS, using single-camera RGR tracking, can reduce spectral artifacts and quantitation errors in Cho/Cr ratios due to head motion and promises improved spectral quality and reproducibility.

We investigated the association of systemic and local tissue stress responses with heat-tolerant (TOL) levels in mice. Thirty-eight mice were assigned into control and three heat exposure groups-TOL, moderately tolerant, and intolerant (INT), based on their overall thermal responses. Real-time core temperature, blood pressure, and heart rate (HR) were assessed during heat exposure (39.5 °C) under conscious condition. Tissue samples were collected 18-22 h following heat exposure. INT mice had significantly higher peak mean arterial pressure and HR than TOL mice during heat exposure. Plasma corticosterone levels were significantly higher in INT than in control mice. No significant changes in plasma cytokines or markers of oxidative status were observed. INT mice showed significant increases in HSP72 and HSP90 protein and mRNA levels in liver, heart, and gastrocnemius muscles compared to TOL and control mice. In contrast, INT mice had significantly lower heat shock factor 1 and glucocorticoid receptor protein and mRNA levels in these tissues than TOL and control mice. These results indicate that acute heat exposure induces stress responses in various tissues of INT mice, but not TOL mice. Upregulation of stress proteins by acute heat exposure involves both transcriptional and translational pathways.

Background Methamphetamine can be neurotoxic to the adult brain; however, many individuals first use methamphetamine during adolescence, and the drug’s impact on this period of brain development is unknown. Therefore, we evaluated young methamphetamine users for possible abnormalities in brain metabolite concentrations. Methods Anterior cingulate cortex (ACC), frontal white matter (FWM), basal ganglia, and thalamus were studied with localized proton magnetic resonance spectroscopy in 54 periadolescent (ages 13–23 years) methamphetamine users and 53 comparison subjects. The concentrations of major brain metabolites and their associations with age, sex and cognition were assessed. Results FWM total-creatine correlated with age in methamphetamine-using males and comparison females, but not comparison males or methamphetamine-using females, leading to a drug by sex by age interaction (p=0.003) and ACC choline-containing compounds (CHO) correlated with age only in comparison males leading to a drug by sex by age interaction (p=0.03). Higher ACC CHO was associated with faster performance on the Stroop Interference task in the control males. Male methamphetamine users had slowest performance on the Stroop Interference task and did not show showed age-appropriate levels of ACC CHO. Conclusions The altered age-appropriate levels of ACC CHO and poorer executive function in male methamphetamine users suggest methamphetamine abuse may interfere with brain maturation. These periadolescents did not have the abnormal neuronal markers previously reported in adult methamphetamine users, suggesting that neuronal abnormalities may be the result of long-term use or interference in normal cortical maturation, emphasizing the need for early intervention for young methamphetamine users.

N-acetylaspartate (NAA) is recognized as a noninvasive diagnostic neuronal marker for a host of neuropsychiatric disorders using magnetic resonance spectroscopy (MRS). Numerous correlative clinical studies have found significant decreases in NAA levels in specific neuronal systems in an array of neuropsychiatric and substance-abuse disorders. We have recently identified the methamphetamine-induced neuronal protein known as "shati" as the NAA biosynthetic enzyme (aspartate N-acetyltransferase [Asp-NAT]; gene Nat8l). We have generated an Nat8l transgenic knockout mouse line to study the functions of NAA in the nervous system. We were unable to breed homozygous Nat8l knockout mice successfully for study and so used the heterozygous mice (Nat8l(+/-) ) for initial characterization. MRS analysis of the Nat8l(+/-) mice indicated significant reductions in NAA in cortex (-38%) and hypothalamus (-29%) compared with wild-type controls, which was confirmed using HPLC (-29% in forebrain). The level of the neuromodulator N-acetylaspartylglutamate (NAAG), which is synthesized from NAA, was decreased by 12% in forebrain as shown by HPLC. Behavioral analyses of the heterozygous animals indicated normal behavior in most respects but reduced vertical activity in open-field tests compared with age- and sex-matched wild-type mice of the same strain. Nat8l(+/-) mice also showed atypical locomotor responses to methamphetamine administration, suggesting that NAA is involved in modulating the hyperactivity effect of methamphetamine. These observations add to accumulating evidence suggesting that NAA has specific regulatory functional roles in mesolimbic and prefrontal neuronal pathways either directly or indirectly through impact on NAAG synthesis

The family of heat shock proteins works at the cellular level to protect cells against many chronically and acutely induced stressful conditions. The induction of certain family members, such as HSP70 and HSP90 via a heat shock factor 1 activated pathway, may have broad therapeutic benefits in the treatment of various types of tissue trauma and metabolic diseases. HSPs with their ability to improve cytoprotective functions and enhance tissue regeneration, offer a new potential in treating conditions such as diabetes and obesity. We hypothesized that the plasma levels of HSP70 and/or HSP90 would be significantly lower in obese than non-obese African American men and women. The objective of the study was to provide an analysis of plasma HSP70 and HSP90 concentrations of African American subjects grouped according to widely accepted health risk indices and insulin resistance. Comparisons of HSP70 and HSP90 concentrations by BMI, percent body fat, waist circumference, insulin resistance, plasma cortisol levels and gender were conducted. HSP70 concentration inversely correlated with BMI, percentage body fat, waist circumference, and insulin resistance. No significant correlation was observed for HSP90 concentration with the aforementioned indices. Our results show that high risk health conditions, such as obesity and type-2 diabetes, may be associated with compromised expression of specific heat shock proteins such as HSP70.

Purpose This study aims to provide a first comparison of the accuracy of two real-time motion tracking systems in the MR environment: MR-based PROspective Motion Correction (PROMO) and optical Moiré Phase Tracking (MPT). Methods Five subjects performed eight predefined head rotations about 8° ± 3° while being simultaneously tracked with PROMO and MPT. Structural images acquired immediately before and after each tracking experiment were realigned with SPM8 to provide a reference measurement. Results Mean signed errors (MSEs) in MPT tracking relative to SPM8 were less than 0.3 mm and 0.2° in all 6 degrees of freedom, and MSEs in PROMO tracking ranged up to 0.2 mm and 0.3°. MPT and PROMO significantly differed from SPM8 in y-translation and y-rotation values (p<0.05). Maximum absolute errors ranged up to 2.8 mm and 2.1° for MPT, and 2.2 mm and 2.9° for PROMO. Conclusion This study presents the first in vivo comparison of MPT and PROMO tracking. Our data shows that two methods yielded similar performances (within 1 mm and 1° standard deviation) relative to reference image registration. Tracking errors of both systems were larger than offline tests. Future work is required for further comparison of two methods in vivo with higher precision.

We investigated the association between heat‐induced stress responses and heat tolerance levels in mice. Thirty‐eight mice were assigned into control and three heat exposure groups ‐ tolerant (TOL), moderately tolerant (MT) and intolerant (INT), based on their thermal responses. Real‐time core temperature, blood pressure, and heart rate were assessed during heat exposure (120 min at 39.5°C) under conscious condition. Tissue samples were collected 18–22 hours following heat exposure. INT mice had significantly higher peak mean arterial pressure and heart rate than TOL mice during heat exposure. Plasma corticosterone levels were significantly higher in INT than control mice. No changes in plasma cytokines or markers of oxidative status were observed. INT mice showed significant increases in HSP72 and HSP90 protein and mRNA levels in liver, heart and gastrocnemius muscles compared to TOL and control mice. In contrast, INT mice had significantly lower HSF1 and glucocorticoid receptor protein and mRNA levels in these tissues than TOL and control mice. These results suggest that heat exposure causes an extensive stress response in mice with heat intolerance. Complex transcriptional and translational processes are involved in mediation of heat‐induced stress. (supported by ONR N0001411MP20025 and USUHS R091EH)