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T1 and T2 quantification using magnetic resonance fingerprinting in mild traumatic brain injury

Gerhalter, Teresa; Cloos, Martijn; Chen, Anna M; Dehkharghani, Seena; Peralta, Rosemary; Babb, James S; Zarate, Alejandro; Bushnik, Tamara; Silver, Jonathan M; Im, Brian S; Wall, Stephen; Baete, Steven; Madelin, Guillaume; Kirov, Ivan I
OBJECTIVES/OBJECTIVE:To assess whether MR fingerprinting (MRF)-based relaxation properties exhibit cross-sectional and prospective correlations with patient outcome and compare the results with those from DTI. METHODS:from MRF were compared in 12 gray and white matter regions with Mann-Whitney tests. Bivariate associations between MR measures and outcome were assessed using the Spearman correlation and logistic regression. RESULTS:, accounted for five of the six MR measures with the highest utility for identification of non-recovered patients at timepoint 2 (AUC > 0.80). CONCLUSION/CONCLUSIONS:, FA, and ADC for predicting 3-month outcome after mTBI. KEY POINTS/CONCLUSIONS:, and FA.
PMID: 34410458
ISSN: 1432-1084
CID: 5006382

Hippocampal single-voxel MR spectroscopy with a long echo time at 3 T using semi-LASER sequence

Gajdošík, Martin; Landheer, Karl; Swanberg, Kelley M; Adlparvar, Fatemeh; Madelin, Guillaume; Bogner, Wolfgang; Juchem, Christoph; Kirov, Ivan I
The hippocampus is one of the most challenging brain regions for proton MR spectroscopy (MRS) applications. Moreover, quantification of J-coupled species such as myo-inositol (m-Ins) and glutamate + glutamine (Glx) is affected by the presence of macromolecular background. While long echo time (TE) MRS eliminates the macromolecules, it also decreases the m-Ins and Glx signal and, as a result, these metabolites are studied mainly with short TE. Here, we investigate the feasibility of reproducibly measuring their concentrations at a long TE of 120 ms, using a semi-adiabatic localization by adiabatic selective refocusing (sLASER) sequence, as this sequence was recently recommended as a standard for clinical MRS. Gradient offset-independent adiabatic refocusing pulses were implemented, and an optimal long TE for the detection of m-Ins and Glx was determined using the T2 relaxation times of macromolecules. Metabolite concentrations and their coefficients of variation (CVs) were obtained for a 3.4-mL voxel centered on the left hippocampus on 3-T MR systems at two different sites with three healthy subjects (aged 32.5 ± 10.2 years [mean ± standard deviation]) per site, with each subject scanned over two sessions, and with each session comprising three scans. Concentrations of m-Ins, choline, creatine, Glx and N-acetyl-aspartate were 5.4 ± 1.5, 1.7 ± 0.2, 5.8 ± 0.3, 11.6 ± 1.2 and 5.9 ± 0.4 mM (mean ± standard deviation), respectively. Their respective mean within-session CVs were 14.5% ± 5.9%, 6.5% ± 5.3%, 6.0% ± 3.4%, 10.6% ± 6.2% and 3.5% ± 1.4%, and their mean within-subject CVs were 17.8% ± 18.2%, 7.5% ± 6.3%, 7.4% ± 6.4%, 12.4% ± 5.3% and 4.8% ± 3.0%. The between-subject CVs were 25.0%, 12.3%, 5.3%, 10.7% and 6.4%, respectively. Hippocampal long-TE sLASER single voxel spectroscopy can provide macromolecule-independent assessment of all major metabolites including Glx and m-Ins.
PMID: 33956374
ISSN: 1099-1492
CID: 4858972

The clinical utility of proton magnetic resonance spectroscopy in traumatic brain injury: recommendations from the ENIGMA MRS working group

Bartnik-Olson, Brenda L; Alger, Jeffry R; Babikian, Talin; Harris, Ashley D; Holshouser, Barbara; Kirov, Ivan I; Maudsley, Andrew A; Thompson, Paul M; Dennis, Emily L; Tate, David F; Wilde, Elisabeth A; Lin, Alexander
Proton (1H) magnetic resonance spectroscopy provides a non-invasive and quantitative measure of brain metabolites. Traumatic brain injury impacts cerebral metabolism and a number of research groups have successfully used this technique as a biomarker of injury and/or outcome in both pediatric and adult TBI populations. However, this technique is underutilized, with studies being performed primarily at centers with access to MR research support. In this paper we present a technical introduction to the acquisition and analysis of in vivo 1H magnetic resonance spectroscopy and review 1H magnetic resonance spectroscopy findings in different injury populations. In addition, we propose a basic 1H magnetic resonance spectroscopy data acquisition scheme (Supplemental Information) that can be added to any imaging protocol, regardless of clinical magnetic resonance platform. We outline a number of considerations for study design as a way of encouraging the use of 1H magnetic resonance spectroscopy in the study of traumatic brain injury, as well as recommendations to improve data harmonization across groups already using this technique.
PMID: 32797399
ISSN: 1931-7565
CID: 4565522

Global decrease in brain sodium concentration after mild traumatic brain injury

Gerhalter, Teresa; Chen, Anna M; Dehkharghani, Seena; Peralta, Rosemary; Adlparvar, Fatemeh; Babb, James S; Bushnik, Tamara; Silver, Jonathan M; Im, Brian S; Wall, Stephen P; Brown, Ryan; Baete, Steven H; Kirov, Ivan I; Madelin, Guillaume
The pathological cascade of tissue damage in mild traumatic brain injury is set forth by a perturbation in ionic homeostasis. However, whether this class of injury can be detected in vivo and serve as a surrogate marker of clinical outcome is unknown. We employ sodium MRI to test the hypotheses that regional and global total sodium concentrations: (i) are higher in patients than in controls and (ii) correlate with clinical presentation and neuropsychological function. Given the novelty of sodium imaging in traumatic brain injury, effect sizes from (i), and correlation types and strength from (ii), were compared to those obtained using standard diffusion imaging metrics. Twenty-seven patients (20 female, age 35.9 ± 12.2 years) within 2 months after injury and 19 controls were scanned with proton and sodium MRI at 3 Tesla. Total sodium concentration, fractional anisotropy and apparent diffusion coefficient were obtained with voxel averaging across 12 grey and white matter regions. Linear regression was used to obtain global grey and white matter total sodium concentrations. Patient outcome was assessed with global functioning, symptom profiles and neuropsychological function assessments. In the regional analysis, there were no statistically significant differences between patients and controls in apparent diffusion coefficient, while differences in sodium concentration and fractional anisotropy were found only in single regions. However, for each of the 12 regions, sodium concentration effect sizes were uni-directional, due to lower mean sodium concentration in patients compared to controls. Consequently, linear regression analysis found statistically significant lower global grey and white matter sodium concentrations in patients compared to controls. The strongest correlation with outcome was between global grey matter sodium concentration and the composite z-score from the neuropsychological testing. In conclusion, both sodium concentration and diffusion showed poor utility in differentiating patients from controls, and weak correlations with clinical presentation, when using a region-based approach. In contrast, sodium linear regression, capitalizing on partial volume correction and high sensitivity to global changes, revealed high effect sizes and associations with patient outcome. This suggests that well-recognized sodium imbalances in traumatic brain injury are (i) detectable non-invasively; (ii) non-focal; (iii) occur even when the antecedent injury is clinically mild. Finally, in contrast to our principle hypothesis, patients' sodium concentrations were lower than controls, indicating that the biological effect of traumatic brain injury on the sodium homeostasis may differ from that in other neurological disorders. Note: This figure has been annotated.
PMID: 33928248
ISSN: 2632-1297
CID: 4852212

Global brain volume and N-acetyl-aspartate decline over seven decades of normal aging

Kirov, Ivan I; Sollberger, Marc; Davitz, Matthew S; Glodzik, Lidia; Soher, Brian J; Babb, James S; Monsch, Andreas U; Gass, Achim; Gonen, Oded
We characterize the whole-brain N-acetyl-aspartate (WBNAA) and brain tissue fractions across the adult lifespan and test the hypothesis that, despite age-related atrophy, neuronal integrity (reflected by WBNAA) is preserved in normal aging. Two-hundred-and-seven participants: 133 cognitively intact older adults (73.6 ± 7.4 mean ± standard deviation, range: 60-90 year old) and 84 young (37.9 ± 11, range: 21-59 year old) were scanned with proton magnetic resonance spectroscopy and T1-weighted MRI. Their WBNAA, fractional brain parenchyma, and gray and white matter volumes (fBPV, fGM, and fWM) were compared and modeled as functions of age and sex. Compared with young, older-adults' WBNAA was lower by ~35%, and fBPV, fGM and fWM were lower by ~10%. Linear regressions found 0.5%/year WBNAA and 0.2%/year fBPV and fGM declines, whereas fWM rose to age ~40 years, and declined thereafter. fBPV and fGM were 1.8% and 4% higher in women, with no sex decline rates difference. We conclude that contrary to our hypothesis, atrophy was accompanied by WBNAA decline. Across the entire age range, women's brains showed less atrophy than men's. Formulas to estimate WBNAA and brain tissue fractions in healthy adults are provided to help differentiate normal from abnormal aging.
PMID: 33232854
ISSN: 1558-1497
CID: 4680542

Potential clinical impact of multiparametric quantitative MR spectroscopy in neurological disorders: A review and analysis

Kirov, Ivan I; Tal, Assaf
PURPOSE/OBJECTIVE:). To test whether knowledge of these additional parameters can improve the clinical utility of brain MRS, we compare the conventional and multiparametric approaches in terms of expected classification accuracy in differentiating controls from patients with neurological disorders. THEORY AND METHODS/UNASSIGNED:(conventional MRS); using metabolite concentrations corrected using per-subject values (multiparametric MRS); and using an optimal linear multiparametric estimator comprised of the metabolites' concentrations and relaxation constants (multiparametric MRS). Additional simulations were conducted to find the minimal intra-subject precision needed for each parameter. RESULTS:Compared with conventional MRS, multiparametric approaches yielded area under the curve improvements for almost all neuropathologies and regions of interest. The median area under the curve increased by 0.14 over the entire dataset, and by 0.24 over the 10 instances with the largest individual increases. CONCLUSIONS:Multiparametric MRS can substantially improve the clinical utility of MRS in diagnosing and assessing brain pathology, motivating the design and use of novel multiparametric sequences.
PMID: 31393032
ISSN: 1522-2594
CID: 4033402

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

Susceptibility-Weighted Imaging and Magnetic Resonance Spectroscopy in Concussion

Kirov, Ivan I; Whitlow, Christopher T; Zamora, Carlos
Although susceptibility-weighted imaging (SWI) studies have suggested an increased number of microhemorrhages in concussion, most show no significant differences compared with controls. There have been mixed results on using SWI to predict neurologic outcomes. Drawbacks include inability to time microhemorrhages and difficulty in attributing them to the concussion. Magnetic resonance spectroscopy (MRS) in concussion can identify metabolic abnormalities, with many studies showing correlations with clinical outcome. Applications in individual patients are impeded by conflicting data and lack of consensus on an optimal protocol. Therefore, currently MRS has most utility in group-level comparisons designed to reveal the pathophysiology of concussion.
PMID: 29157856
ISSN: 1557-9867
CID: 2791632

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