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Decreased basal ganglia and thalamic iron in early psychotic spectrum disorders are associated with increased psychotic and schizotypal symptoms

Sui, Yu Veronica; McKenna, Faye; Bertisch, Hilary; Storey, Pippa; Anthopolos, Rebecca; Goff, Donald C; Samsonov, Alexey; Lazar, Mariana
Iron deficits have been reported as a risk factor for psychotic spectrum disorders (PSD). However, examinations of brain iron in PSD remain limited. The current study employed quantitative MRI to examine iron content in several iron-rich subcortical structures in 49 young adult individuals with PSD (15 schizophrenia, 17 schizoaffective disorder, and 17 bipolar disorder with psychotic features) compared with 35 age-matched healthy controls (HC). A parametric approach based on a two-pool magnetization transfer model was applied to estimate longitudinal relaxation rate (R1), which reflects both iron and myelin, and macromolecular proton fraction (MPF), which is specific to myelin. To describe iron content, a synthetic effective transverse relaxation rate (R2*) was modeled using a linear fitting of R1 and MPF. PSD patients compared to HC showed significantly reduced R1 and synthetic R2* across examined regions including the pallidum, ventral diencephalon, thalamus, and putamen areas. This finding was primarily driven by decreases in the subgroup with schizophrenia, followed by schizoaffective disorder. No significant group differences were noted for MPF between PSD and HC while for regional volume, significant reductions in patients were only observed in bilateral caudate, suggesting that R1 and synthetic R2* reductions in schizophrenia and schizoaffective patients likely reflect iron deficits that either occur independently or precede structural and myelin changes. Subcortical R1 and synthetic R2* were also found to be inversely related to positive symptoms within the PSD group and to schizotypal traits across the whole sample. These findings that decreased iron in subcortical regions are associated with PSD risk and symptomatology suggest that brain iron deficiencies may play a role in PSD pathology and warrant further study.
PMID: 36071113
ISSN: 1476-5578
CID: 5332512

Flow Patterns and Particle Residence Times in the Oral Cavity during Inhaled Drug Delivery

Vara Almirall, Brenda; Inthavong, Kiao; Bradshaw, Kimberley; Singh, Narinder; Johnson, Aaron; Storey, Pippa; Salati, Hana
Pulmonary drug delivery aims to deliver particles deep into the lungs, bypassing the mouth-throat airway geometry. However, micron particles under high flow rates are susceptible to inertial impaction on anatomical sites that serve as a defense system to filter and prevent foreign particles from entering the lungs. The aim of this study was to understand particle aerodynamics and its possible deposition in the mouth-throat airway that inhibits pulmonary drug delivery. In this study, we present an analysis of the aerodynamics of inhaled particles inside a patient-specific mouth-throat model generated from MRI scans. Computational Fluid Dynamics with a Discrete Phase Model for tracking particles was used to characterize the airflow patterns for a constant inhalation flow rate of 30 L/min. Monodisperse particles with diameters of 7 μm to 26 μm were introduced to the domain within a 3 cm-diameter sphere in front of the oral cavity. The main outcomes of this study showed that the time taken for particle deposition to occur was 0.5 s; a narrow stream of particles (medially and superiorly) were transported by the flow field; larger particles > 20 μm deposited onto the oropharnyx, while smaller particles < 12 μm were more disperse throughout the oral cavity and navigated the curved geometry and laryngeal jet to escape through the tracheal outlet. It was concluded that at a flow rate of 30 L/min the particle diameters depositing on the larynx and trachea in this specific patient model are likely to be in the range of 7 μm to 16 μm. Particles larger than 16 μm primarily deposited on the oropharynx.
PMID: 36297371
ISSN: 1424-8247
CID: 5359532

Higher body mass index is associated with worse hippocampal vasoreactivity to carbon dioxide

Glodzik, Lidia; Rusinek, Henry; Butler, Tracy; Li, Yi; Storey, Pippa; Sweeney, Elizabeth; Osorio, Ricardo S; Biskaduros, Adrienne; Tanzi, Emily; Harvey, Patrick; Woldstad, Christopher; Maloney, Thomas; de Leon, Mony J
Background and objectives/UNASSIGNED:) in a group of cognitively normal middle-aged and older adults. Methods/UNASSIGNED:Our study was a retrospective analysis of prospectively collected data. Subjects were enrolled for studies assessing the role of hippocampal hemodynamics as a biomarker for AD among cognitively healthy elderly individuals (age > 50). Participants without cognitive impairment, stroke, and active substance abuse were recruited between January 2008 and November 2017 at the NYU Grossman School of Medicine, former Center for Brain Health. All subjects underwent medical, psychiatric, and neurological assessments, blood tests, and MRI examinations. To estimate CVR, we increased their carbon dioxide levels using a rebreathing protocol. Relationships between BMI and brain measures were tested using linear regression. Results/UNASSIGNED:in women (β = -0.20, unstandardized B = -0.08, 95% CI -0.13, -0.02). Discussion/UNASSIGNED:These findings lend support to the notion that obesity is a risk factor for hippocampal hemodynamic impairment and suggest targeting obesity as an important prevention strategy. Prospective studies assessing the effects of weight loss on brain hemodynamic measures and inflammation are warranted.
PMID: 36158536
ISSN: 1663-4365
CID: 5333982

Inverse Relationships Between Basal Ganglia Iron and Positive Psychotic Symptoms in Early Psychotic Spectrum Disorders [Meeting Abstract]

Sui, Yu Veronica; McKenna, Faye; Bertisch, Hilary; Storey, Pippa; Anthopolos, Rebecca; Goff, Donald C.; Samsonov, Alexey; Lazar, Mariana
ISSN: 0006-3223
CID: 5386482

Bilateral gradient-echo spectroscopic imaging with correction of frequency variations for measurement of fatty acid composition in mammary adipose tissue

Baboli, Mehran; Storey, Pippa; Sood, Terlika Pandit; Fogarty, Justin; Moccaldi, Melanie; Lewin, Alana; Moy, Linda; Kim, Sungheon Gene
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 ± standard deviation frequency drift of 17.4 ± 2.5 Hz, with ripples at 0.3 ± 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 ± 10.6%, 18.5 ± 13.9%, and 18.4 ± 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.
PMID: 33533056
ISSN: 1522-2594
CID: 4788292

Quantitative Macromolecular Proton Fraction Mapping Reveals Altered Cortical Myelin Profile in Schizophrenia Spectrum Disorders

Sui, Yu Veronica; Bertisch, Hilary; Lee, Hong-Hsi; Storey, Pippa; Babb, James S; Goff, Donald C; Samsonov, Alexey; Lazar, Mariana
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 (>5.5 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.
PMID: 34296161
ISSN: 2632-7376
CID: 4948622

MR Susceptibility Imaging with a Short TE (MR-SISET): A Clinically Feasible Technique to Resolve Thalamic Nuclei

Chung, S; Storey, P; Shepherd, T M; Lui, Y W
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.
PMID: 32675340
ISSN: 1936-959x
CID: 4529162

Fatty acid composition in mammary adipose tissue measured by Gradient-echo Spectroscopic MRI and its association with breast cancers

Lewin, Alana A; Storey, Pippa; Moccaldi, Melanie; Moy, Linda; Gene Kim, S
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 (0.336 ± 0.038) in mammary adipose tissue compared to those with benign disease (0.283 ± 0.046, p = 0.0008) and to those with a history of breast cancer (0.287 ± 0.050, p = 0.0038). Postmenopausal women with malignant lesions had significantly lower MUFA (0.352 ± 0.041) compared to those with benign disease (0.401 ± 0.043, p = 0.0032) and with history of breast cancer (0.388 ± 0.055, p = 0.0484). The history of cancer group had a significant correlation (r = 0.60, p = 0.006) between SFA and BMI, and the cancer group had a significant correlation (r = 0.57, p = 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.
PMID: 31153566
ISSN: 1872-7727
CID: 3923212

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

Lim, Ruth P; Singh, Susan G; Hornsey, Emma; Kearney, Leighton; Churilov, Leonid; Storey, Pippa; Begbie, Mark; Shoobridge, Jennifer; Xu, Jian; Rayner, Melanie; Matalanis, George; Smith, Gerard
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 ≥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.
PMID: 30664117
ISSN: 1532-3145
CID: 3783162

Different Relationship Between Systolic Blood Pressure and Cerebral Perfusion in Subjects With and Without Hypertension

Glodzik, Lidia; Rusinek, Henry; Tsui, Wai; Pirraglia, Elizabeth; Kim, Hee-Jin; Deshpande, Anup; Li, Yi; Storey, Pippa; Randall, Catherine; Chen, Jingyun; Osorio, Ricardo S; Butler, Tracy; Tanzi, Emily; McQuillan, Molly; Harvey, Patrick; Williams, Stephen K; Ogedegbe, Gbenga; Babb, James S; de Leon, Mony J
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.
PMID: 30571554
ISSN: 1524-4563
CID: 3556742