P581. Inverse Relationships Between Basal Ganglia Iron and Positive Psychotic Symptoms in Early Psychotic Spectrum Disorders [Meeting Abstract]
Background: Iron is critical for healthy brain biochemistry and function. While deficient peripheral iron was found to increase psychiatric morbidity risk, in vivo brain iron examinations in psychotic spectrum disorders (PSD) are lacking. Here, we examined tissue iron changes in PSD and their associations with psychotic symptoms in iron-rich basal ganglia structures and thalamus using MRI.
Method(s): Combining quantitative magnetization transfer imaging and linear regression modeling, we generated R1, macromolecular proton fraction (MPF), and synthetic R2* in 49 young-adult PSD individuals (age 18-35; 15 schizophrenia; 17 schizoaffective; 17 bipolar with psychotic features) and 39 age-matched healthy controls (HC). R2* and MPF are known to reflect tissue iron and myelin content respectively, while R1 reflects both. Clinical symptoms were evaluated using the Scales for the Assessment of Negative/Positive Symptoms (SANS/SAPS). The Benjamini-Hochberg multiple comparison correction was used.
Result(s): Decreased R1 and synthetic R2* were observed in schizophrenia versus HC in pallidum, thalamus, putamen, and ventral diencephalon (p<0.05), with R2* being more sensitive to between-group differences than R1. Schizoaffective and bipolar individuals showed less extensive changes. Neither MPF nor structure volume was significantly different among groups. In PSD individuals, R1 and R2* were inversely correlated with SAPS across examined regions (Spearman's rho between -0.34 and -0.49, p<0.05).
Conclusion(s): Our results suggest decreased basal ganglia and thalamic iron in PSD, most extensively in schizophrenia. Decreased subcortical iron is associated with increased positive symptoms and appears to be either independent from or preceding volumetric and myelin changes. These findings suggest iron as a potential treatment target in PSD. Supported By: R01MH108962; R01EB027087 Keywords: Psychotic Disorders, Brain Iron, Schizophrenia, Basal Ganglia, Thalamus
Bilateral gradient-echo spectroscopic imaging with correction of frequency variations for measurement of fatty acid composition in mammary adipose tissue
PURPOSE/OBJECTIVE:To develop a simultaneous dual-slab three-dimensional gradient-echo spectroscopic imaging (GSI) technique with frequency drift compensation for rapid (<6 min) bilateral measurement of fatty acid composition (FAC) in mammary adipose tissue. METHODS:A bilateral GSI sequence was developed using a simultaneous dual-slab excitation followed by 128 monopolar echoes. A short train of navigator echoes without phase or partition encoding was included at the beginning of each pulse repetition time period to correct for frequency variation caused by respiration and heating of the cryostat. Voxel-wise spectral fitting was applied to measure the areas of the lipid spectral peaks to estimate the number of double-bond (ndb), number of methylene-interrupted double-bond (nmidb), and chain length (cl). The proposed method was tested in an oil phantom and 10 postmenopausal women to assess the influence of the frequency variation on FAC estimation. RESULTS:The frequency drift observed over 5:27 min during the phantom scan was about 10 Hz. Phase correction based on the navigator reduced the median error of ndb, nmidb, and cl from 9.7%, 17.6%, and 3.2% to 2.1%, 9.5%, and 2.8%, respectively. The in vivo data showed a mean Â± standard deviation frequency drift of 17.4 Â± 2.5 Hz, with ripples at 0.3 Â± 0.1 Hz. Our reconstruction algorithm successfully separated signals from the left and right breasts with negligible residual aliasing. Phase correction reduced the interquartile range within each subject's adipose tissue of ndb, nmidb, and cl by 18.4 Â± 10.6%, 18.5 Â± 13.9%, and 18.4 Â± 10.6%, respectively. CONCLUSION/CONCLUSIONS:This study shows the feasibility of obtaining bilateral spectroscopic imaging data in the breast and that incorporation of a frequency navigator improves the estimation of FAC.
Quantitative Macromolecular Proton Fraction Mapping Reveals Altered Cortical Myelin Profile in Schizophrenia Spectrum Disorders
Myelin abnormalities have been reported in schizophrenia spectrum disorders (SSD) in white matter. However, in vivo examinations of cortical myeloarchitecture in SSD, especially those using quantitative measures, are limited. Here, we employed macromolecular proton fraction (MPF) obtained from quantitative magnetization transfer imaging to characterize intracortical myelin organization in 30 SSD patients versus 34 healthy control (HC) participants. We constructed cortical myelin profiles by extracting MPF values at various cortical depths and quantified their shape using a nonlinearity index (NLI). To delineate the association of illness duration with myelin changes, SSD patients were further divided into 3 duration groups. Between-group comparisons revealed reduced NLI in the SSD group with the longest illness duration (>5.5Â years) compared with HC predominantly in bilateral prefrontal areas. Within the SSD group, cortical NLI decreased with disease duration and was positively associated with a measure of spatial working memory capacity as well as with cortical thickness (CT). Layer-specific analyses suggested that NLI decreases in the long-duration SSD group may arise in part from significantly increased MPF values in the midcortical layers. The current study reveals cortical myelin profile changes in SSD with illness progression, which may reflect an abnormal compensatory mechanism of the disorder.
MR Susceptibility Imaging with a Short TE (MR-SISET): A Clinically Feasible Technique to Resolve Thalamic Nuclei
The thalamus consists of several functionally distinct nuclei, some of which serve as targets for functional neurosurgery. Visualization of such nuclei is a major challenge due to their low signal contrast on conventional imaging. We introduce MR susceptibility imaging with a short TE, leveraging susceptibility differences among thalamic nuclei, to automatically delineate 15 thalamic subregions. The technique has the potential to enable direct targeting of thalamic nuclei for functional neurosurgical guidance.
Fatty acid composition in mammary adipose tissue measured by Gradient-echo Spectroscopic MRI and its association with breast cancers
PURPOSE/OBJECTIVE:To assess the association of fatty acid levels in mammary adipose tissue of postmenopausal women with the presence of breast cancer using the Gradient-echo Spectroscopic Imaging (GSI). MATERIALS AND METHODS/METHODS:test, one-way analysis of variance (ANOVA) with Tukey-Kramer multiple comparison tests, and linear regression. RESULTS:Postmenopausal women with malignancies had significantly higher SFA (0.336â€‰Â±â€‰0.038) in mammary adipose tissue compared to those with benign disease (0.283â€‰Â±â€‰0.046, pâ€‰=â€‰0.0008) and to those with a history of breast cancer (0.287â€‰Â±â€‰0.050, pâ€‰=â€‰0.0038). Postmenopausal women with malignant lesions had significantly lower MUFA (0.352â€‰Â±â€‰0.041) compared to those with benign disease (0.401â€‰Â±â€‰0.043, pâ€‰=â€‰0.0032) and with history of breast cancer (0.388â€‰Â±â€‰0.055, pâ€‰=â€‰0.0484). The history of cancer group had a significant correlation (râ€‰=â€‰0.60, pâ€‰=â€‰0.006) between SFA and BMI, and the cancer group had a significant correlation (râ€‰=â€‰0.57, pâ€‰=â€‰0.010) between PUFA and BMI. CONCLUSIONS:Fatty acid composition of mammary adipose tissue, particularly higher SFA and lower MUFA, may be associated with breast cancer. The GSI method utilizes an automated voxel-based analysis to measure fatty acid composition, and may be used to assess the role of mammary adipose tissue in cancer development and progress.
Highly Accelerated Breath-Hold Noncontrast Electrocardiographically- and Pulse-Gated Balanced Steady-State Free Precession Magnetic Resonance Angiography of the Thoracic Aorta: Comparison With Electrocardiographically-Gated Computed Tomographic Angiography
OBJECTIVE:The aim of this study was to evaluate agreement of measured thoracic aortic caliber in patients with aortic disease, using electrocardiographically-(ECG) and pulse-gated breath-hold noncontrast balanced steady-state free precession MRA (ECG-MRA, P-MRA) at 1.5 T, compared with ECG-gated computed tomographic angiography (CTA). METHODS:Thirty-one patients underwent ECG-MRA, P-MRA, and CTA. Two readers independently measured aortic caliber in 7 segments, with agreement between techniques and readers evaluated. Image quality was qualitatively assessed. RESULTS:There was overall excellent agreement among ECG-MRA, P-MRA, and CTA for measured aortic caliber (Lin's concordance correlation coefficient â‰¥0.94, all comparisons); however, lower concordance was noted at the annulus (Lin's concordance correlation coefficient <0.6) at segmental assessment. There was excellent interreader agreement for aortic caliber for all 3 techniques (intraclass correlation coefficient >0.94). Image quality was poorer for both MRA techniques compared with CTA, particularly at the aortic root. CONCLUSIONS:Electrocardiographically-gated MRA and P-MRA at 1.5 T achieve comparable thoracic aortic measurements to gated CTA in clinical patients, despite inferior image quality.
Different Relationship Between Systolic Blood Pressure and Cerebral Perfusion in Subjects With and Without Hypertension
Although there is an increasing agreement that hypertension is associated with cerebrovascular compromise, relationships between blood pressure (BP) and cerebral blood flow are not fully understood. It is not known what BP level, and consequently what therapeutic goal, is optimal for brain perfusion. Moreover, there is limited data on how BP affects hippocampal perfusion, a structure critically involved in memory. We conducted a cross-sectional (n=445) and longitudinal (n=185) study of adults and elderly without dementia or clinically apparent stroke, who underwent clinical examination and brain perfusion assessment (age 69.2Â±7.5 years, 62% women, 45% hypertensive). Linear models were used to test baseline BP-blood flow relationship and to examine how changes in BP influence changes in perfusion. In the entire group, systolic BP (SBP) was negatively related to cortical (Î²=-0.13, P=0.005) and hippocampal blood flow (Î²=-0.12, P=0.01). Notably, this negative relationship was apparent already in subjects without hypertension. Hypertensive subjects showed a quadratic relationship between SBP and hippocampal blood flow (Î²=-1.55, P=0.03): Perfusion was the highest in subjects with mid-range SBP around 125 mmâ€‰Hg. Longitudinally, in hypertensive subjects perfusion increased with increased SBP at low baseline SBP but increased with decreased SBP at high baseline SBP. Cortical and hippocampal perfusion decrease with increasing SBP across the entire BP spectrum. However, in hypertension, there seems to be a window of mid-range SBP which maximizes perfusion.
Brown fat activation, sleep restriction and obesity [Meeting Abstract]
Background: The prevalence of short sleep duration (defined as obtaining less than 7 h of sleep/night), affecting more than 33% of the general adult population, has major implications for health since it is associated with an increased risk of obesity, type 2 diabetes, hypertension, cardiovascular disease, mental disorders and cancers. Brown adipose tissue (BAT) has recently emerged as a tissue that may be of importance in preventing the development of obesity- and diabetesrelated chronic disorders. Interestingly, animal studies have suggested that adequate or high-quality rebound sleep after sleep restriction (SR) may be dependent upon functional BAT. The goal of the proposed study is to evaluate the impact of SR on BAT activation after 3 nights of SR in healthy adults. Methods: After a 3-d period of habitual sleep (HS, 8 h sleep/night) and sleep restriction (SR, 4 h sleep/night) under identical, controlled, weight maintenance feeding conditions, BAT activities were assessed by a PET/MR combined scanner with simultaneous acquisition (Biograph mMR, Siemens) using 18F-FDG, under the same mild cold stimulation conditions as described for our previous study. Using Firevoxel (https://urldefense.proofpoint.com/v2/url?u=https- 3A__wp.nyu.edu_Firevoxel&d=DwIBAg&c=j5oPpO0eBH1iio48DtsedbOBGmuw5jHLjgvtN2r4ehE&r=KRXe NoRy5_8lkSwAJG5vjS1yT0aFSItfe494dmkdSVs&m=8NZWXYcQ5x1dTVrT2ZfItUAstuZhFSmX8FNg_yC6Xs8 &s=nuei0hazHFtuK2V7h2WfDcHQkWWU4wp7DvxYsqA65Dc&e=), regions of interests, including BAT and muscle (a reference region), were drawn on several coronal planes of FDG-PET and MR-fat fused images that containing BAT. TheSUVmean and SUVR (ratio of SUV BAT/muscle) were calculated. The fat fraction (FF) and R2[asterisk](= 1/T2[asterisk]) in BAT were quantified using a new, improved sequence (the Siemens 3D multi-echo works-in-progress package). Blood samples were collected and assayed to determine circulating levels of orexin, thyroid hormones (TSH and T4), insulin, cortisol, appetite hormones (leptin, ghrelin) and SNS markers, and correlated with BAT thermogenesis. Results and Discussions: SUVR normalized to the subjects' blood glucose levels measured prior to the 2 scans were compared. The results from our preliminary study showed different SUVR values for subjects between HS and SR with ~20% increase in BAT activity in response to SR (n=4). The FF in BAT measured during the simultaneously acquired PET/MR data showed a mean increase of ~15%. These results support our hypothesis that BAT activation was greater after sleep loss as compared to HS, and consistent with our previous results that 24-h energy expenditure (EE), measured in a metabolic chamber, was increased after SR (~7%). Furthermore, there were good correlations between BAT activation and various metabolic markers: SUVR-HS and BMI (Pearson r=-0.85), SUVR-SR and insulin (r=-0.99), SUVR-SR and insulin resistance index (HOMA-IR, r=-0.98). It was noted that the participant with the least BAT activation had highest insulin, HOMA-IR, and leptin levels. Conclusion: Our preliminary studies showed the relation between BAT thermogenesis and sleep, suggesting its implication for health. This study, which evaluated the impact of SR on BAT and its role on RecS, will provide information on the function of BAT that will be relevant for individuals with sleep disorders and those at risk of obesity and its associated chronic metabolic conditions; namely type 2 diabetes, hypertension, and cardiovascular disease. The outcome of this study may provide further insight for treatment related to sleep disorders and obesity by providing information on the physiological role of BAT in sleep homeostasis
Quantitative Proton Spectroscopy of the Testes at 3 T: Toward a Noninvasive Biomarker of Spermatogenesis
OBJECTIVES: The aim of this study was to compare testicular metabolite concentrations between fertile control subjects and infertile men. MATERIALS AND METHODS: Single voxel proton magnetic resonance spectroscopy ((1)H-MRS) was performed in the testes with and without water suppression at 3 T in 9 fertile control subjects and 9 infertile patients (8 with azoospermia and 1 with oligospermia). In controls only, the T1 and T2 values of water and metabolites were also measured. Absolute metabolite concentrations were calculated using the unsuppressed water signal as a reference and correcting for the relative T1 and T2 weighting of the water and metabolite signals. RESULTS: Testicular T1 values of water, total choline, and total creatine were 2028 +/- 125 milliseconds, 1164 +/- 105 milliseconds, and 1421 +/- 314 milliseconds, respectively (mean +/- standard deviation). T2 values were 154 +/- 11 milliseconds, 342 +/- 53 milliseconds, and 285 +/- 167 milliseconds, respectively. Total choline concentration was lower in patients (mean, 1.5 mmol/L; range, 0.9-2.1 mmol/L) than controls (mean, 4.4 mmol/L; range, 3.2-5.7 mmol/L; P = 4 x 10(-)(5)). Total creatine concentration was likewise reduced in patients (mean, 1.1 mmol/L; range, undetectable -2.7 mmol/L) compared with controls (mean, 3.6 mmol/L; range, 2.5-4.7 mmol/L; P = 1.6 x 10(-)(4)). The myo-inositol signal normalized to the water reference was also lower in patients than controls (P = 4 x 10(-)(5)). CONCLUSIONS: Testicular metabolite concentrations, measured by proton spectroscopy at 3 T, may be valuable as noninvasive biomarkers of spermatogenesis.
Insulin resistance among obese middle-aged is associated with decreased cerebrovascular reactivity
OBJECTIVE: To evaluate differences in cerebrovascular reactivity (CVR) to mild hypercapnia in obese/overweight individuals with and without insulin resistance (IR) compared to comparable lean controls. METHODS: A total of 60 cognitively normal participants (20 lean controls and 24 obese/overweight individuals with and 16 without IR) were evaluated using a high spatial resolution arterial spin labeling MRI technique at rest and during mild hypercapnia. We analyzed group differences in CVR in cerebral cortex and ascertained the relationships between CVR, IR, and body mass index (BMI). RESULTS: Obese/overweight participants with and without IR had significantly lower CVR to hypercapnia than lean controls after controlling for age, sex, and the presence of hypertension (F2,53 = 5.578, p = 0.006 eta2p = 0.174). In the obese/overweight participants with IR, there was a significant correlation between higher CVR and a measure of insulin sensitivity, even after accounting for BMI (rp = 0.575, p = 0.004). In contrast, there was no relationship between CVR and BMI when controlling for IR. No such relationships existed for the other 2 groups. CONCLUSIONS: IR is associated with impaired CVR; the relationship appears to be driven by the degree of IR and not by obesity. These rarely reported results suggest that early forms of cerebrovascular dysfunction exist among obese middle-aged individuals with significant IR but without type 2 diabetes mellitus. These functional vascular abnormalities may help explain the associations among IR, diabetes, and dementia, and suggest that interventions aiming to improve IR or CVR may help prevent cognitive decline later in life.