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The neutrophil to lymphocyte ratio associates with markers of Alzheimer"™s disease pathology in cognitively unimpaired elderly people

Jacobs, Tovia; Jacobson, Sean R.; Fortea, Juan; Berger, Jeffrey S.; Vedvyas, Alok; Marsh, Karyn; He, Tianshe; Gutierrez-Jimenez, Eugenio; Fillmore, Nathanael R.; Gonzalez, Moses; Figueredo, Luisa; Gaggi, Naomi L.; Plaska, Chelsea Reichert; Pomara, Nunzio; Blessing, Esther; Betensky, Rebecca; Rusinek, Henry; Zetterberg, Henrik; Blennow, Kaj; Glodzik, Lidia; Wisniweski, Thomas M.; de Leon, Mony J.; Osorio, Ricardo S.; Ramos-Cejudo, Jaime
Background: An elevated neutrophil"“lymphocyte ratio (NLR) in blood has been associated with Alzheimer"™s disease (AD). However, an elevated NLR has also been implicated in many other conditions that are risk factors for AD, prompting investigation into whether the NLR is directly linked with AD pathology or a result of underlying comorbidities. Herein, we explored the relationship between the NLR and AD biomarkers in the cerebrospinal fluid (CSF) of cognitively unimpaired (CU) subjects. Adjusting for sociodemographics, APOE4, and common comorbidities, we investigated these associations in two cohorts: the Alzheimer"™s Disease Neuroimaging Initiative (ADNI) and the M.J. de Leon CSF repository at NYU. Specifically, we examined associations between the NLR and cross-sectional measures of amyloid-β42 (Aβ42), total tau (t-tau), and phosphorylated tau181 (p-tau), as well as the trajectories of these CSF measures obtained longitudinally. Results: A total of 111 ADNI and 190 NYU participants classified as CU with available NLR, CSF, and covariate data were included. Compared to NYU, ADNI participants were older (73.79 vs. 61.53, p < 0.001), had a higher proportion of males (49.5% vs. 36.8%, p = 0.042), higher BMIs (27.94 vs. 25.79, p < 0.001), higher prevalence of hypertensive history (47.7% vs. 16.3%, p < 0.001), and a greater percentage of Aβ-positivity (34.2% vs. 20.0%, p = 0.009). In the ADNI cohort, we found cross-sectional associations between the NLR and CSF Aβ42 (β = -12.193, p = 0.021), but not t-tau or p-tau. In the NYU cohort, we found cross-sectional associations between the NLR and CSF t-tau (β = 26.812, p = 0.019) and p-tau (β = 3.441, p = 0.015), but not Aβ42. In the NYU cohort alone, subjects classified as Aβ + (n = 38) displayed a stronger association between the NLR and t-tau (β = 100.476, p = 0.037) compared to Aβ- subjects or the non-stratified cohort. In both cohorts, the same associations observed in the cross-sectional analyses were observed after incorporating longitudinal CSF data. Conclusions: We report associations between the NLR and Aβ42 in the older ADNI cohort, and between the NLR and t-tau and p-tau in the younger NYU cohort. Associations persisted after adjusting for comorbidities, suggesting a direct link between the NLR and AD. However, changes in associations between the NLR and specific AD biomarkers may occur as part of immunosenescence.
ISSN: 1742-4933
CID: 5658902

Signatures of microstructure in gradient-echo and spin-echo signals

Storey, Pippa; Novikov, Dmitry S
PURPOSE/OBJECTIVE:To determine whether the spatial scale and magnetic susceptibility of microstructure can be evaluated robustly from the decay of gradient-echo and spin-echo signals. THEORY AND METHODS/METHODS:Gradient-echo and spin-echo images were acquired from suspensions of spherical polystyrene microbeads of 10, 20, and 40 μm nominal diameter. The sizes of the beads and their magnetic susceptibility relative to the medium were estimated from the signal decay curves, using a lookup table generated from Monte Carlo simulations and an analytic model based on the Gaussian phase approximation. RESULTS:Fitting Monte Carlo predictions to spin-echo data yielded acceptable estimates of microstructural parameters for the 20 and 40 μm microbeads. Using gradient-echo data, the Monte Carlo lookup table provided satisfactory parameter estimates for the 20 μm beads but unstable results for the diameter of the largest beads. Neither spin-echo nor gradient-echo data allowed accurate parameter estimation for the smallest beads. The analytic model performed poorly over all bead sizes. CONCLUSIONS:Microstructural sources of magnetic susceptibility produce distinctive non-exponential signatures in the decay of gradient-echo and spin-echo signals. However, inverting the problem to extract microstructural parameters from the signals is nontrivial and, in certain regimes, ill-conditioned. For microstructure with small characteristic length scales, parameter estimation is hampered by the difficulty of acquiring accurate data at very short echo times. For microstructure with large characteristic lengths, the gradient-echo signal approaches the static-dephasing regime, where it becomes insensitive to size. Applicability of the analytic model was further limited by failure of the Gaussian phase approximation for all but the smallest beads.
PMID: 38520259
ISSN: 1522-2594
CID: 5641072

Designing Clinical MRI for Enhanced Workflow and Value

Lin, Dana J; Doshi, Ankur M; Fritz, Jan; Recht, Michael P
MRI is an expensive and traditionally time-intensive modality in imaging. With the paradigm shift toward value-based healthcare, radiology departments must examine the entire MRI process cycle to identify opportunities to optimize efficiency and enhance value for patients. Digital tools such as "frictionless scheduling" prioritize patient preference and convenience, thereby delivering patient-centered care. Recent advances in conventional and deep learning-based accelerated image reconstruction methods have reduced image acquisition time to such a degree that so-called nongradient time now constitutes a major percentage of total room time. For this reason, architectural design strategies that reconfigure patient preparation processes and decrease the turnaround time between scans can substantially impact overall throughput while also improving patient comfort and privacy. Real-time informatics tools that provide an enterprise-wide overview of MRI workflow and Picture Archiving and Communication System (PACS)-integrated instant messaging can complement these efforts by offering transparent, situational data and facilitating communication between radiology team members. Finally, long-term investment in training, recruiting, and retaining a highly skilled technologist workforce is essential for building a pipeline and team of technologists committed to excellence. Here, we highlight various opportunities for optimizing MRI workflow and enhancing value by offering many of our own on-the-ground experiences and conclude by anticipating some of the future directions for process improvement and innovation in clinical MR imaging. EVIDENCE LEVEL: N/A TECHNICAL EFFICACY: Stage 1.
PMID: 37795927
ISSN: 1522-2586
CID: 5664522

Functional Connectivity Changes on Resting-State fMRI after Mild Traumatic Brain Injury: A Systematic Review

Dogra, Siddhant; Arabshahi, Soroush; Wei, Jason; Saidenberg, Lucia; Kang, Stella K; Chung, Sohae; Laine, Andrew; Lui, Yvonne W
BACKGROUND:Mild traumatic brain injury is theorized to cause widespread functional changes to the brain. Resting-state fMRI may be able to measure functional connectivity changes after traumatic brain injury, but resting-state fMRI studies are heterogeneous, using numerous techniques to study ROIs across various resting-state networks. PURPOSE/OBJECTIVE:We systematically reviewed the literature to ascertain whether adult patients who have experienced mild traumatic brain injury show consistent functional connectivity changes on resting-state -fMRI, compared with healthy patients. DATA SOURCES/METHODS:We used 5 databases (PubMed, EMBASE, Cochrane Central, Scopus, Web of Science). STUDY SELECTION/METHODS:Five databases (PubMed, EMBASE, Cochrane Central, Scopus, and Web of Science) were searched for research published since 2010. Search strategies used keywords of "functional MR imaging" and "mild traumatic brain injury" as well as related terms. All results were screened at the abstract and title levels by 4 reviewers according to predefined inclusion and exclusion criteria. For full-text inclusion, each study was evaluated independently by 2 reviewers, with discordant screening settled by consensus. DATA ANALYSIS/METHODS:Data regarding article characteristics, cohort demographics, fMRI scan parameters, data analysis processing software, atlas used, data characteristics, and statistical analysis information were extracted. DATA SYNTHESIS/RESULTS:Across 66 studies, 80 areas were analyzed 239 times for at least 1 time point, most commonly using independent component analysis. The most analyzed areas and networks were the whole brain, the default mode network, and the salience network. Reported functional connectivity changes varied, though there may be a slight trend toward decreased whole-brain functional connectivity within 1 month of traumatic brain injury and there may be differences based on the time since injury. LIMITATIONS/CONCLUSIONS:Studies of military, sports-related traumatic brain injury, and pediatric patients were excluded. Due to the high number of relevant studies and data heterogeneity, we could not be as granular in the analysis as we would have liked. CONCLUSIONS:Reported functional connectivity changes varied, even within the same region and network, at least partially reflecting differences in technical parameters, preprocessing software, and analysis methods as well as probable differences in individual injury. There is a need for novel rs-fMRI techniques that better capture subject-specific functional connectivity changes.
PMID: 38637022
ISSN: 1936-959x
CID: 5664742

Multisite MRI Intravoxel Incoherent Motion Repeatability and Reproducibility across 3 T Scanners in a Breast Diffusion Phantom: A BReast Intravoxel Incoherent Motion Multisite (BRIMM) Study

Basukala, Dibash; Mikheev, Artem; Sevilimedu, Varadan; Gilani, Nima; Moy, Linda; Pinker, Katja; Thakur, Sunitha B; Sigmund, Eric E
BACKGROUND:Monoexponential apparent diffusion coefficient (ADC) and biexponential intravoxel incoherent motion (IVIM) analysis of diffusion-weighted imaging is helpful in the characterization of breast tumors. However, repeatability/reproducibility studies across scanners and across sites are scarce. PURPOSE/OBJECTIVE:)) within and across sites employing MRI scanners from different vendors utilizing 16-channel breast array coils in a breast diffusion phantom. STUDY TYPE/METHODS:Phantom repeatability. PHANTOM/UNASSIGNED:A breast phantom containing tubes of different polyvinylpyrrolidone (PVP) concentrations, water, fat, and sponge flow chambers, together with an MR-compatible liquid crystal (LC) thermometer. FIELD STRENGTH/SEQUENCE/UNASSIGNED:Bipolar gradient twice-refocused spin echo sequence and monopolar gradient single spin echo sequence at 3 T. ASSESSMENT/RESULTS:Studies were performed twice in each of two scanners, located at different sites, on each of 2 days, resulting in four studies per scanner. ADCs of the PVP and water were normalized to the vendor-provided calibrated values at the temperature indicated by the LC thermometer for repeatability/reproducibility comparisons. STATISTICAL TESTS/METHODS:ADC and IVIM repeatability and reproducibility within and across sites were estimated via the within-system coefficient of variation (wCV). Pearson correlation coefficient (r) was also computed between IVIM metrics and flow speed. A P value <0.05 was considered statistically significant. RESULTS:correlations with flow speed were significant at both sites. DATA CONCLUSION/CONCLUSIONS:. LEVEL OF EVIDENCE/METHODS:2 TECHNICAL EFFICACY: Stage 1.
PMID: 37702382
ISSN: 1522-2586
CID: 5593502

Reduced oxygen extraction fraction in deep cerebral veins associated with cognitive impairment in multiple sclerosis

Sawan, Hasan; Li, Chenyang; Buch, Sagar; Bernitsas, Evanthia; Haacke, E Mark; Ge, Yulin; Chen, Yongsheng
Studying the relationship between cerebral oxygen utilization and cognitive impairment is essential to understanding neuronal functional changes in the disease progression of multiple sclerosis (MS). This study explores the potential of using venous susceptibility in internal cerebral veins (ICVs) as an imaging biomarker for cognitive impairment in relapsing-remitting MS (RRMS) patients. Quantitative susceptibility mapping derived from fully flow-compensated MRI phase data was employed to directly measure venous blood oxygen saturation levels (SvO2) in the ICVs. Results revealed a significant reduction in the susceptibility of ICVs (212.4 ± 30.8 ppb vs 239.4 ± 25.9 ppb) and a significant increase of SvO2 (74.5 ± 1.89% vs 72.4 ± 2.23%) in patients with RRMS compared with age- and sex-matched healthy controls. Both the susceptibility of ICVs (r = 0.508, p = 0.031) and the SvO2 (r = -0.498, p = 0.036) exhibited a moderate correlation with cognitive decline in these patients assessed by the Paced Auditory Serial Addition Test, while no significant correlation was observed with clinical disability measured by the Expanded Disability Status Scale. The findings suggest that venous susceptibility in ICVs has the potential to serve as a specific indicator of oxygen metabolism and cognitive function in RRMS. .
PMID: 38820447
ISSN: 1559-7016
CID: 5664002

Longitudinal trajectories of Alzheimer's disease CSF biomarkers and blood pressure in cognitively healthy subjects

Biskaduros, Adrienne; Glodzik, Lidia; Saint Louis, Leslie A; Rusinek, Henry; Pirraglia, Elizabeth; Osorio, Ricardo; Butler, Tracy; Li, Yi; Xi, Ke; Tanzi, Emily; Harvey, Patrick; Zetterberg, Henrik; Blennow, Kaj; de Leon, Mony J
INTRODUCTION/BACKGROUND:We examined whether hypertension (HTN) was associated with Alzheimer's disease-related biomarkers in cerebrospinal fluid (CSF) and how changes in blood pressure (BP) related to changes in CSF biomarkers over time. METHODS:A longitudinal observation of cognitively healthy normotensive subjects (n = 134, BP < 140/90, with no antihypertensive medication), controlled HTN (n = 36, BP < 140/90, taking antihypertensive medication), and 35 subjects with uncontrolled HTN (BP ≥ 140/90). The follow-up range was 0.5to15.6 years. RESULTS:Total tau (T-tau) and phospho-tau181 (P-tau 181) increased in all but controlled HTN subjects (group×time interaction: p < 0.05 for both), but no significant Aβ42 changes were seen. Significant BP reduction was observed in uncontrolled HTN, and it was related to increase in T-tau (p = 0.001) and P-tau 181 (p < 0.001). DISCUSSION/CONCLUSIONS:Longitudinal increases in T-tau and P-tau 181 were observed in most subjects; however, only uncontrolled HTN had both markers increase alongside BP reductions. We speculate cumulative vascular injury renders the brain susceptible to relative hypoperfusion with BP reduction. HIGHLIGHTS/CONCLUSIONS:Over the course of the study, participants with uncontrolled HTN at baseline showed greater accumulation of CSF total tau and phospho-tau181 (P-tau 181) than subjects with normal BP or with controlled HTN. In the group with uncontrolled HTN, increases in total tau and P-tau 181 coincided with reduction in BP. We believe this highlights the role of HTN in vascular injury and suggests decline in cerebral perfusion resulting in increased biomarker concentrations in CSF. Medication use was the main factor differentiating controlled from uncontrolled HTN, indicating that earlier treatment was beneficial for preventing accumulations of pathology.
PMID: 38808676
ISSN: 1552-5279
CID: 5663512

Engineered coiled-coil HIF1α protein domain mimic

Britton, Dustin; Katsara, Olga; Mishkit, Orin; Wang, Andrew; Pandya, Neelam; Liu, Chengliang; Mao, Heather; Legocki, Jakub; Jia, Sihan; Xiao, Yingxin; Aristizabal, Orlando; Paul, Deven; Deng, Yan; Schneider, Robert; Wadghiri, Youssef Z; Montclare, Jin Kim
The development of targeted anti-cancer therapeutics offers the potential for increased efficacy of drugs and diagnostics. Utilizing modalities agnostic to tumor type, such as the hypoxic tumor microenvironment (TME), may assist in the development of universal tumor targeting agents. The hypoxia-inducible factor (HIF), in particular HIF1, plays a key role in tumor adaptation to hypoxia, and inhibiting its interaction with p300 has been shown to provide therapeutic potential. Using a multivalent assembled protein (MAP) approach based on the self-assembly of the cartilage oligomeric matrix protein coiled-coil (COMPcc) domain fused to the critical residues of the C-terminal transactivation domain (C-TAD) of the α subunit of HIF1 (HIF1α), we generate HIF1α-MAP (H-MAP). The resulting H-MAP demonstrates picomolar binding affinity to p300, the ability to downregulate hypoxia-inducible genes, and in vivo tumor targeting capability.
PMID: 38656316
ISSN: 2047-4849
CID: 5663092

Digital reference object toolkit of breast DCE MRI for quantitative evaluation of image reconstruction and analysis methods

Bae, Jonghyun; Tan, Zhengguo; Solomon, Eddy; Huang, Zhengnan; Heacock, Laura; Moy, Linda; Knoll, Florian; Kim, Sungheon Gene
PURPOSE/OBJECTIVE:To develop a digital reference object (DRO) toolkit to generate realistic breast DCE-MRI data for quantitative assessment of image reconstruction and data analysis methods. METHODS: RESULTS: CONCLUSION/CONCLUSIONS:We have developed a DRO toolkit that includes realistic morphology of tumor lesions along with the expected pharmacokinetic parameter ranges. This simulation framework can generate many images for quantitative assessment of DCE-MRI reconstruction and analysis methods.
PMID: 38775077
ISSN: 1522-2594
CID: 5654602

Accelerated MRI reconstructions via variational network and feature domain learning

Giannakopoulos, Ilias I; Muckley, Matthew J; Kim, Jesi; Breen, Matthew; Johnson, Patricia M; Lui, Yvonne W; Lattanzi, Riccardo
We introduce three architecture modifications to enhance the performance of the end-to-end (E2E) variational network (VarNet) for undersampled MRI reconstructions. We first implemented the Feature VarNet, which propagates information throughout the cascades of the network in an N-channel feature-space instead of a 2-channel feature-space. Then, we add an attention layer that utilizes the spatial locations of Cartesian undersampling artifacts to further improve performance. Lastly, we combined the Feature and E2E VarNets into the Feature-Image (FI) VarNet, to facilitate cross-domain learning and boost accuracy. Reconstructions were evaluated on the fastMRI dataset using standard metrics and clinical scoring by three neuroradiologists. Feature and FI VarNets outperformed the E2E VarNet for 4
PMID: 38744904
ISSN: 2045-2322
CID: 5656142