Faculty Bibliography

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 69.2±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 (β=-0.13, P=0.005) and hippocampal blood flow (β=-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 (β=-1.55, P=0.03): Perfusion was the highest in subjects with mid-range SBP around 125 mm 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.

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

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.

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.

Purpose To demonstrate the feasibility of the use of a rapid, noninvasive, in vivo imaging method to measure fatty acid fractions of breast adipose tissue during diagnostic breast magnetic resonance (MR) examinations and to investigate associations between fatty acid fractions in breast adipose tissue and breast cancer status by using this method. Materials and Methods The institutional review board approved this retrospective HIPAA-compliant study and informed consent was waived. Between July 2013 and September 2014, multiple-echo three-dimensional gradient-echo data were acquired for 89 women. Spectra were generated and used to estimate fractions of monounsaturated fatty acid (MUFA), polyunsaturated fatty acid (PUFA), and saturated fatty acid (SFA) in the breast adipose tissue. Analysis of covariance and exact Mann-Whitney tests were used to compare groups and the Spearman rank correlation coefficient was used to characterize the association of each imaging measure with each attribute. Results For postmenopausal women, MUFA was lower (0.38 +/- 0.06 vs 0.46 +/- 0.10; P < .05) and SFA was higher (0.31 +/- 0.07 vs 0.19 +/- 0.11; P < .05) for women with invasive ductal carcinoma than for those with benign tissue. No correlation was found between body mass index (BMI) and fatty acid fractions in breast adipose tissue. In women with benign tissue, postmenopausal women had a higher PUFA (0.35 +/- 0.06 vs 0.27 +/- 0.05; P < .01) and lower SFA (0.19 +/- 0.11 vs 0.30 +/- 0.12; P < .05) than premenopausal women. Conclusion There is a possible link between the presence of invasive ductal carcinoma and fatty acid fractions in breast adipose tissue for postmenopausal women in whom BMI values are not correlated with the fatty acid fractions. (c) RSNA, 2016 Online supplemental material is available for this article.

PURPOSE: Perfusion analysis from first-pass contrast enhancement kinetics requires modeling tissue contrast exchange. This study presents a new approach for numerical implementation of the tissue homogeneity model, incorporating flexible distance steps along the capillary (NTHf). METHODS: The proposed NTHf model considers contrast exchange in fluid packets flowing along the capillary, incorporating flexible distance steps, thus allowing more efficient and stable calculations of the transit of tracer through the tissue. We prospectively studied 8 patients (62 +/- 13 years old) with suspected CAD, who underwent first-pass perfusion CMR imaging at rest and stress prior to angiography. Myocardial blood flow (MBF) and myocardial perfusion reserve index (MPRI) were estimated using both the NTHf and the conventional adiabatic approximation of the TH models. Coronary artery lesions detected at angiography were clinically assigned to one of three categories of stenosis severity ('insignificant', 'mild to moderate' and 'severe') and related to corresponding myocardial territories. RESULTS: The mean MBF (ml/g/min) at rest/stress and MPRI were 0.80 +/- 0.33/1.25 +/- 0.45 and 1.68 +/- 0.54 in the insignificant regions, 0.74 +/- 0.21/1.09 +/- 0.28 and 1.54 +/- 0.46 in the mild to moderate regions, and 0.79 +/- 0.28/0.63 +/- 0.34 and 0.85 +/- 0.48 in the severe regions, respectively. The correlation coefficients of MBFs at rest/stress and MPRI between the NTHf and AATH models were r = 0.97/0.93 and r = 0.91, respectively. CONCLUSIONS: The proposed NTHf model allows efficient quantitative analysis of the transit of tracer through tissue, particularly at higher flow. Results of initial application to MRI of myocardial perfusion in CAD are encouraging.

PURPOSE: R2* (1/T2*) and single echo R2 (1/T2) have been calibrated to liver iron concentration (LIC) in patients with thalassemia and transfusion-dependent sickle cell disease at 1.5T. The R2*-LIC relationship is linear, whereas that of R2 is curvilinear. However, the increasing popularity of high-field scanners requires generalizing these relationships to higher field strengths. In this study, we tested the hypothesis that numerical simulation can accurately determine the field dependence of iron-mediated transverse relaxation rates. METHODS: We previously replicated the calibration curves between R2 and R2* and iron at 1.5T using Monte Carlo models incorporating realistic liver structure, iron deposit susceptibility, and proton mobility. In this paper, we extend our model to predict relaxivity-iron calibrations at higher field strengths. Predictions were validated by measuring R2 and R2* at 1.5T and 3T in six beta-thalassemia major patients. RESULTS: Predicted R2* increased twofold at 3T from 1.5T, whereas R2 increased by a factor of 1.47. Patient data exhibited a coefficient of variation of 3.6% and 7.2%, respectively, to the best-fit simulated data. Simulations over the range 0.25T-7T showed R2* increasing linearly with field strength, whereas R2 exhibited a concave-downward relationship. CONCLUSION: A model-based approach predicts alterations in relaxivity-iron calibrations with field strength without repeating imaging studies. The model may generalize to alternative pulse sequences and tissue iron distribution. Magn Reson Med, 2014. (c) 2014 Wiley Periodicals, Inc.

OBJECTIVES: Fresh blood imaging (FBI) is a useful noncontrast magnetic resonance angiographic (MRA) method for the assessment of peripheral arterial disease, particularly for imaging patients with poor renal function. Compared with 1.5 T, 3 T enables higher signal-to-noise ratio and/or spatiotemporal resolution in FBI. Indeed, previous studies have reported successful FBI of the calf station at 3 T. However, FBI of the thigh station at 3 T has been reported to suffer from signal void in the common femoral artery of 1 thigh only because of the radial symmetry in transmit radiofrequency field (B1+) variation. We sought to increase the signal of femoral artery in FBI at 3 T using high-permittivity dielectric padding. MATERIALS AND METHODS: We performed FBI and B1+ mapping of the thigh station at 3 T in 13 human subjects to compare the following 3 dielectric padding settings: no padding, commercially available thick (approximately 5 cm) dielectric padding, and high-permittivity thin (approximately 2 cm) dielectric padding. We characterized the radial symmetry in B1+ variation as well as its impact on the FBI signal at baseline and how dielectric padding improves B1+ and FBI. We evaluated the quality of 3 FBI MRA acquisitions using quantitative (ie, contrast-to-noise ratio of femoral arteries) and qualitative (ie, conspicuity of femoral arteries) analyses. RESULTS: With the subjects positioned on the magnetic resonance table in feet-first, supine orientation, the radial symmetry in B1+ variation attenuates the signal in the right common femoral artery. The signal void can be improved partially with commercial padding and improved further with high-permittivity padding. Averaging the results over the 13 subjects, the mean B1+, contrast-to-noise ratio, and conspicuity scores for the right common femoral artery were significantly higher with high-permittivity padding than with commercial padding and baseline (P < 0.001). CONCLUSIONS: Our study shows that high-permittivity dielectric padding can be used to increase the signal of femoral artery in FBI at 3 T.

Cerebral perfusion was evaluated in 87 subjects prospectively enrolled in three study groups-healthy controls (HC), patients with insulin resistance (IR) but not with diabetes, and type 2 diabetes mellitus (T2DM). Participants received a comprehensive 8-hour clinical evaluation and arterial spin labeling magnetic resonance imaging (MRI). In order of decreasing significance, an association was found between cerebral blood flow (CBF) and sex, waist circumference, diastolic blood pressure (BP), end tidal CO2, and verbal fluency score (R2=0.27, F=5.89, P<0.001). Mean gray-matter CBF in IR was 4.4 mL/100 g per minute lower than in control subjects (P=0.005), with no hypoperfusion in T2DM (P=0.312). Subjects with IR also showed no CO2 relationship (slope=-0.012) in the normocapnic range, in contrast to a strong relationship in healthy brains (slope=0.800) and intermediate response (slope=0.445) in diabetic patients. Since the majority of T2DM but few IR subjects were aggressively treated with blood glucose, cholesterol, and BP lowering medications, our finding could be attributed to the beneficial effect of these drugs.Journal of Cerebral Blood Flow & Metabolism advance online publication, 15 October 2014; doi:10.1038/jcbfm.2014.173.