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Hippocampal metabolite concentrations in schizophrenia vary in association with rare gene variants in the TRIO gene [Letter]

Malaspina, Dolores; Gonen, Oded; Rhodes, Haley; Hoffman, Kevin W; Heguy, Adriana; Walsh-Messinger, Julie; Chao, Moses V; Kranz, Thorsten M
PMID: 33183947
ISSN: 1573-2509
CID: 4671882

Putamen Inflammation and its Association With Working Memory Impairments in Schizophrenia Spectrum Disorders [Meeting Abstract]

Gupta, Pradeep Kumar; Gonen, Oded; Goff, Donald; Bertisch, Hilary; Lazar, Mariana
ISSN: 0006-3223
CID: 4560832

Quantitative multivoxel proton MR spectroscopy for the identification of white matter abnormalities in mild traumatic brain injury: Comparison between regional and global analysis

Davitz, Matthew S; Gonen, Oded; Tal, Assaf; Babb, James S; Lui, Yvonne W; Kirov, Ivan I
BACKGROUND:H MRS with the ability to separate tissue-type partial volume contribution(s). PURPOSE/OBJECTIVE:H MRSI voxel averaging is sensitive to regional WM metabolic abnormalities. STUDY TYPE/METHODS:Retrospective cross-sectional cohort study. POPULATION/METHODS:Twenty-seven subjects: 15 symptomatic mTBI patients, 12 matched controls. FIELD STRENGTH/SEQUENCE/UNASSIGNED:. ASSESSMENT/RESULTS:N-acetyl-aspartate (NAA), creatine, choline, and myo-inositol concentrations estimated in predominantly WM regions: body, genu, and splenium of the corpus callosum, corona radiata, frontal, and occipital WM. STATISTICAL TESTS/UNASSIGNED:Analysis of covariance (ANCOVA) to compare patients with controls in terms of regional concentrations. The effect sizes (Cohen's d) of the mean differences were compared across regions and with previously published global data obtained with linear regression of the WM over the entire VOI in the same dataset. RESULTS:Despite patients' global VOI WM NAA being significantly lower than the controls', no regional differences were observed for any metabolite. Regional NAA comparisons, however, were all unidirectional (patients' NAA concentrations < controls') within a narrow range: 0.3 ≤ Cohen's d ≤ 0.6. DATA CONCLUSION/UNASSIGNED:H MRS studies, given that these results are confirmed in other cohorts. LEVEL OF EVIDENCE/METHODS:2 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2019.
PMID: 30868703
ISSN: 1522-2586
CID: 3733342

Erratum to "Whole brain neuronal abnormalities in focal epilepsy quantified with proton MR spectroscopy" [Epilepsy Res. 139 (2018) 85-91] [Correction]

Kirov, Ivan I; Kuzniecky, Ruben; Hetherington, Hoby P; Soher, Brian J; Davitz, Matthew S; Babb, James S; Pardoe, Heath R; Pan, Jullie W; Gonen, Oded
PMID: 29656982
ISSN: 1872-6844
CID: 3042952

Receptor Protein Tyrosine Phosphatases in Schizophrenia [Meeting Abstract]

Malaspina, Dolores; Kranz, Thorsten; Gonen, Oded; Harrock, Sheila; Chao, Moses
ISSN: 0006-3223
CID: 3147802

Quantitative Proton Spectroscopy of the Testes at 3 T: Toward a Noninvasive Biomarker of Spermatogenesis

Storey, Pippa; Gonen, Oded; Rosenkrantz, Andrew B; Khurana, Kiranpreet K; Zhao, Tiejun; Bhatta, Rajesh; Alukal, Joseph P
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.
PMID: 28877046
ISSN: 1536-0210
CID: 2688672

Whole brain neuronal abnormalities in focal quantified with proton MR spectroscopy

Kirov, Ivan I; Kuzniecky, Ruben; Hetherington, Hoby P; Soher, Brian J; Davitz, Matthew S; Babb, James S; Pardoe, Heath R; Pan, Jullie W; Gonen, Oded
OBJECTIVE:To test the hypothesis that localization-related epilepsy is associated with widespread neuronal dysfunction beyond the ictal focus, reflected by a decrease in patients' global concentration of their proton MR spectroscopy (1H-MRS) observed marker, N-acetyl-aspartate (NAA). METHODS:Thirteen patients with localization-related epilepsy (7 men, 6 women) 40±13 (mean±standard-deviation)years old, 8.3±13.4years of disease duration; and 14 matched controls, were scanned at 3 T with MRI and whole-brain (WB) 1H MRS. Intracranial fractions of brain volume, gray and white matter (fBV, fGM, fWM) were segmented from the MRI, and global absolute NAA creatine (Cr) and choline (Cho) concentrations were estimated from their WB 1H MRS. These metrics were compared between patients and controls using an unequal variance t test. RESULTS:Patients' fBV, fGM and fWM: 0.81±0.07, 0.47±0.04, 0.31±0.04 were not different from controls' 0.79±0.05, 0.48±0.04, 0.32±0.02; nor were their Cr and Cho concentrations: 7.1±1.1 and 1.3±0.2 millimolar (mM) versus 7.7±0.7 and 1.4±0.1mM (p>0.05 all). Patients' global NAA concentration: 11.5±1.5 mM, however, was 12% lower than controls' 13.0±0.8mM (p=0.004). CONCLUSIONS:These findings indicate that neuronal dysfunction in localization-related epilepsy extends globally, beyond the ictal zone, but without atrophy or spectroscopic evidence of other pathology. This suggests a diffuse decline in the neurons' health, rather than their number, early in the disease course. WB 1H-MRS assessment, therefore, may be a useful tool for quantification of global neuronal dysfunction load in epilepsy.
PMID: 29212047
ISSN: 1872-6844
CID: 2861722

Diagnosis of Normal-Pressure Hydrocephalus: Use of Traditional Measures in the Era of Volumetric MR Imaging

Miskin, Nityanand; Patel, Hersh; Franceschi, Ana M; Ades-Aron, Benjamin; Le, Alexander; Damadian, Brianna E; Stanton, Christian; Serulle, Yafell; Golomb, James; Gonen, Oded; Rusinek, Henry; George, Ajax E
Purpose To assess the diagnostic performance of the callosal angle (CA) and Evans index (EI) measures and to determine their role versus automated volumetric methods in clinical radiology. Materials and Methods Magnetic resonance (MR) examinations performed before surgery (within 1-5 months of the MR examination) in 36 shunt-responsive patients with normal-pressure hydrocephalus (NPH; mean age, 75 years; age range, 58-87 years; 26 men, 10 women) and MR examinations of age- and sex-matched patients with Alzheimer disease (n = 34) and healthy control volunteers (n = 36) were studied. Three blinded observers independently measured EI and CA for each patient. Volumetric segmentation of global gray matter, white matter, ventricles, and hippocampi was performed by using software. These measures were tested by using multivariable logistic regression models to determine which combination of metrics is most accurate in diagnosis. Results The model that used CA and EI demonstrated 89.6%-93.4% accuracy and average area under the curve of 0.96 in differentiating patients with NPH from patients without NPH (ie, Alzheimer disease and healthy control). The regression model that used volumetric predictors of gray matter and white matter was 94.3% accurate. Conclusion CA and EI may serve as a screening tool to help the radiologist differentiate patients with NPH from patients without NPH, which would allow for designation of patients for further volumetric assessment. (c) RSNA, 2017.
PMID: 28498794
ISSN: 1527-1315
CID: 2548722

Global brain metabolic quantification with whole-head proton MRS at 3 T

Kirov, Ivan I; Wu, William E; Soher, Brian J; Davitz, Matthew S; Huang, Jeffrey H; Babb, James S; Lazar, Mariana; Fatterpekar, Girish; Gonen, Oded
Total N-acetyl-aspartate + N-acetyl-aspartate-glutamate (NAA), total creatine (Cr) and total choline (Cho) proton MRS (1 H-MRS) signals are often used as surrogate markers in diffuse neurological pathologies, but spatial coverage of this methodology is limited to 1%-65% of the brain. Here we wish to demonstrate that non-localized, whole-head (WH) 1 H-MRS captures just the brain's contribution to the Cho and Cr signals, ignoring all other compartments. Towards this end, 27 young healthy adults (18 men, 9 women), 29.9 +/- 8.5 years old, were recruited and underwent T1 -weighted MRI for tissue segmentation, non-localizing, approximately 3 min WH 1 H-MRS (TE /TR /TI = 5/10/940 ms) and 30 min 1 H-MR spectroscopic imaging (MRSI) (TE /TR = 35/2100 ms) in a 360 cm3 volume of interest (VOI) at the brain's center. The VOI absolute NAA, Cr and Cho concentrations, 7.7 +/- 0.5, 5.5 +/- 0.4 and 1.3 +/- 0.2 mM, were all within 10% of the WH: 8.6 +/- 1.1, 6.0 +/- 1.0 and 1.3 +/- 0.2 mM. The mean NAA/Cr and NAA/Cho ratios in the WH were only slightly higher than the "brain-only" VOI: 1.5 versus 1.4 (7%) and 6.6 versus 5.9 (11%); Cho/Cr were not different. The brain/WH volume ratio was 0.31 +/- 0.03 (brain approximately 30% of WH volume). Air-tissue susceptibility-driven local magnetic field changes going from the brain outwards showed sharp gradients of more than 100 Hz/cm (1 ppm/cm), explaining the skull's Cr and Cho signal losses through resonance shifts, line broadening and destructive interference. The similarity of non-localized WH and localized VOI NAA, Cr and Cho concentrations and their ratios suggests that their signals originate predominantly from the brain. Therefore, the fast, comprehensive WH-1 H-MRS method may facilitate quantification of these metabolites, which are common surrogate markers in neurological disorders.
PMID: 28678429
ISSN: 1099-1492
CID: 2617322

Neuropsychological Testing, MR Spectroscopy and Patient Symptom Reports Reveal Two Distinct Stories in mTBI...American Congress of Rehabilitation Medicine Annual Conference 23 - 28 October 2017, Atlanta, GA

Kucukboyaci, Nuri Erkut; Gonen, Oded; Lui, Yvonne; Rath, Joseph; Kirov, Ivan
ISSN: 0003-9993
CID: 2735442