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Item A Preliminary Study of Anatomical Changes Following the Use of a Pedicled Buccal Fat Pad Flap During Primary Palatoplasty(Sage, 2022-05) Kotlarek, Katelyn J.; Jaskolka, Michael S.; Fang, Xiangming; Ellis, Charles; Blemker, Silvia S.; Horswell, Bruce; Kloostra, Paul; Perry, Jamie L.; Oral Pathology, Medicine and Radiology, School of DentistryObjective: The purpose of this study was to examine the surgical impact of the pedicled BFP flap on the LVP muscle and surrounding VP anatomy following primary palatoplasty. Design: Observational, prospective Setting: MRI studies were completed at 3 imaging facilities. All participants with BFP flap were operated on by the same surgeon. Participants: Five pediatric participants with CP±L who underwent primary palatoplasty with BFP flap placement. Comparison groups consisted of 10 participants: 5 with CP±L who did not receive the BFP flap and 5 healthy controls. Interventions: All participants underwent nonsedated MRI 2–5 years postoperatively. Main Outcomes and Measures: Anatomical measures of the velopharynx and LVP among the 3 participant groups Results: Median values were significantly different among groups for velar length (p = .042), effective velar length (p = .048), effective VP ratio (p = .046), LVP length (p = .021), extravelar LVP length (p = .009), and LVP origin-origin distance (p = .030). Post hoc analysis revealed a statistically significant difference between the BFP and traditional repair groups for effective VP ratio (p = .040), extravelar LVP length (p = .033), and LVP length (p = .022). Conclusions: This study provides preliminary support that the BFP flap creates a longer velum, with increased distance between the posterior hard palate and the LVP, and a larger effective VP ratio compared to traditional surgical techniques. Future research is needed to determine if this procedure provides a more favorable mechanism for VP closure.Item A role for zinc transporter gene SLC39A12 in the nervous system and beyond(Elsevier, 2021) Davis, Danielle N.; Strong, Morgan D.; Chambers, Emily; Hart, Matthew D.; Bettaieb, Ahmed; Clarke, Stephen L.; Smith, Brenda J.; Stoecker, Barbara J.; Lucas, Edralin A.; Lin, Dingbo; Chowanadisai, Winyoo; Obstetrics and Gynecology, School of MedicineThe SLC39A12 gene encodes the zinc transporter protein ZIP12, which is expressed across many tissues and is highly abundant in the vertebrate nervous system. As a zinc transporter, ZIP12 functions to transport zinc across cellular membranes, including cellular zinc influx across the plasma membrane. Genome-wide association and exome sequencing studies have shown that brain susceptibility-weighted magnetic resonance imaging (MRI) intensity is associated with ZIP12 polymorphisms and rare mutations. ZIP12 is required for neural tube closure and embryonic development in Xenopus tropicalis. Frog embryos depleted of ZIP12 by antisense morpholinos develop an anterior neural tube defect and lack viability. ZIP12 is also necessary for neurite outgrowth and mitochondrial function in mouse neural cells. ZIP12 mRNA is increased in brain regions of schizophrenic patients. Outside of the nervous system, hypoxia induces ZIP12 expression in multiple mammalian species, including humans, which leads to endothelial and smooth muscle thickening in the lung and contributes towards pulmonary hypertension. Other studies have associated ZIP12 with other diseases such as cancer. Given that ZIP12 is highly expressed in the brain and that susceptibility-weighted MRI is associated with brain metal content, ZIP12 may affect neurological diseases and psychiatric illnesses such as Parkinson's disease, Alzheimer's disease, and schizophrenia. Furthermore, the induction of ZIP12 and resultant zinc uptake under pathophysiological conditions may be a critical component of disease pathology, such as in pulmonary hypertension. Drug compounds that bind metals like zinc may be able to treat diseases associated with impaired zinc homeostasis and altered ZIP12 function.Item Accuracy of MRI in Assessment of High-Grade Partial Distal Biceps Tears(Sage, 2025) Schmidt, Gregory J.; Fischer, James P.; Hoyer, Reed W.; Greenberg, Jeffrey A.; Crosby, Nicholas E.; Graduate Medical Education, School of MedicineBackground: Magnetic resonance imaging (MRI) is commonly used to diagnose and assess the extent of partial distal biceps injuries. The aim of this study was to report on the accuracy of MRI and the effect of injury history and study timing on its performance. Methods: A retrospective review of all patients who underwent surgical treatment of partial thickness distal biceps tears at a single center by multiple surgeons was performed. Inclusion criteria consisted of the performance of a preoperative MRI and documentation of the intraoperatively visualized extent of the tear, and 68 patients met the criteria for inclusion. A chart review was completed to evaluate the symptom duration, injury history, and tear extent. Results: All patients had distal biceps tears of greater than 50% intraoperatively. However, MRI did not indicate any tearing in 20 (29%) patients, and its sensitivity for high-grade tear was 44%. Magnetic resonance imaging was significantly less likely to be read as high-grade tears in patients with insidious onset of their symptoms in comparison with patients who reported a traumatic onset (27% vs 55%, P = .024). However, the time from symptom onset to MRI did not significantly correlate with diagnosis of a high-grade tear on MRI (r = -0.15, P = .21). Conclusions: These results indicate that MRI can underreport partial distal biceps tear extent, and this more commonly occurs in patients with insidious onset of pain.Item Accurate Intramyocardial Hemorrhage Assessment with Fast, Free-running, Cardiac Quantitative Susceptibility Mapping(Radiological Society of North America, 2024) Huang, Yuheng; Guan, Xingmin; Zhang, Xinheng; Yoosefian, Ghazal; Ho, Hao; Huang, Li-Ting; Lin, Hsin-Yao; Anthony, Gregory; Lee, Hsu-Lei; Bi, Xiaoming; Han, Fei; Chan, Shing Fai; Vora, Keyur P.; Sharif, Behzad; Singh, Dhirendra P.; Youssef, Khalid; Li, Debiao; Han, Hui; Christodoulou, Anthony G.; Dharmakumar, Rohan; Yang, Hsin-Jung; Medicine, School of MedicinePurpose: To evaluate the performance of a high-dynamic-range quantitative susceptibility mapping (HDR-QSM) cardiac MRI technique to detect intramyocardial hemorrhage (IMH) and quantify iron content using phantom and canine models. Materials and Methods: A free-running whole-heart HDR-QSM technique for IMH assessment was developed and evaluated in calibrated iron phantoms and 14 IMH female canine models. IMH detection and iron content quantification performance of this technique was compared with the conventional iron imaging approaches, R2*(1/T2*) maps, using measurements from ex vivo imaging as the reference standard. Results: Phantom studies confirmed HDR-QSM’s accurate iron content quantification and artifact mitigation ability by revealing a strong linear relationship between iron concentration and QSM values (R2, 0.98). In in vivo studies, HDR-QSM showed significantly improved image quality and susceptibility homogeneity in nonaffected myocardium by alleviating motion and off-resonance artifacts (HDR-QSM vs R2*: coefficient of variation, 0.31 ± 0.16 [SD] vs 0.73 ± 0.36 [P < .001]; image quality score [five-point Likert scale:], 3.58 ± 0.75 vs 2.87 ± 0.51 [P < .001]). Comparison between in vivo susceptibility maps and ex vivo measurements showed higher performance of HDR-QSM compared with R2* mapping for IMH detection (area under the receiver operating characteristic curve, 0.96 vs 0.75; P < .001) and iron content quantification (R2, 0.71 vs 0.14). Conclusion: In a canine model of IMH, the fast and free-running cardiac QSM technique accurately detected IMH and quantified intramyocardial iron content of the entire heart within 5 minutes without requiring breath holding.Item Aducanumab: Appropriate Use Recommendations(Springer, 2021) Cummings, J.; Aisen, P.; Apostolova, L.G.; Atri, A.; Salloway, S.; Weiner, M.; Neurology, School of MedicineAducanumab has been approved by the US Food and Drug Administration for treatment of Alzheimer's disease (AD). Clinicians require guidance on the appropriate use of this new therapy. An Expert Panel was assembled to construct Appropriate Use Recommendations based on the participant populations, conduct of the pivotal trials of aducanumab, updated Prescribing Information, and expert consensus. Aducanumab is an amyloid-targeting monoclonal antibody delivered by monthly intravenous infusions. The pivotal trials included patients with early AD (mild cognitive impairment due to AD and mild AD dementia) who had confirmed brain amyloid using amyloid positron tomography. The Expert Panel recommends that use of aducanumab be restricted to this population in which efficacy and safety have been studied. Aducanumab is titrated to a dose of 10 mg/kg over a 6-month period. The Expert Panel recommends that the aducanumab be titrated to the highest dose to maximize the opportunity for efficacy. Aducanumab can substantially increase the incidence of amyloid-related imaging abnormalities (ARIA) with brain effusion or hemorrhage. Dose interruption or treatment discontinuation is recommended for symptomatic ARIA and for moderate-severe ARIA. The Expert Panel recommends MRIs prior to initiating therapy, during the titration of the drug, and at any time the patient has symptoms suggestive of ARIA. Recommendations are made for measures less cumbersome than those used in trials for the assessment of effectiveness in the practice setting. The Expert Panel emphasized the critical importance of engaging in a process of patient-centered informed decision-making that includes comprehensive discussions and clear communication with the patient and care partner regarding the requirements for therapy, the expected outcome of therapy, potential risks and side effects, and the required safety monitoring, as well as uncertainties regarding individual responses and benefits.Item Aducanumab: Appropriate Use Recommendations Update(Springer, 2022-04-05) Cummings, Jeffrey; Rabinovici, G. D.; Atri, A.; Aisen, P.; Apostolova, L. G.; Hendrix, S.; Sabbagh, M.; Selkoe, D.; Weiner, M.; Salloway, S.; Alzheimer’s Disease and Related Disorders Therapeutics Working Group; Neurology, School of MedicineAducanumab (Aduhelm) is approved in the United States for the treatment of patients with mild cognitive impairment due to Alzheimer’s disease or mild AD dementia. Aducanumab Appropriate Use Recommendations (AURs) have been published and have helped guide best practices for use of aducanumab. As real-world use has occurred and more information has accrued, the AURs require refinement. We update the AURs to better inform appropriate patient selection and improve shared decision-making, safety monitoring, and risk mitigation in treated patients. Based on evolving experience we emphasize the importance of detecting past medical conditions that may predispose to amyloid related imaging abnormalities (ARIA) or may increase the likelihood of ARIA complications including autoimmune or inflammatory conditions, seizures, or disorders associated with extensive white matter pathology. The apolipoprotein E ε4 (APOE4) genotype is strongly associated with ARIA and exhibits a gene dose effect. We recommend that clinicians perform APOE genotyping to better inform patient care decisions, discussions regarding risk, and clinician vigilance concerning ARIA. As most ARIA occurs during the titration period of aducanumab, we suggest performing MRI before the 5th, 7th, 9th, and 12th infusions to improve detection. Uncommonly, ARIA may be recurrent or serious; we suggest additional parameters for treatment discontinuation taking these observations into account. It is important to continue to learn from the real-world use of aducanumab and the AURs will continue to evolve as new information becomes available. This AUR update does not address efficacy, price, or insurance coverage and is provided to assist clinicians to establish best practices for use of aducanumab in the treatment of patients with mild cognitive impairment and mild Alzheimer’s dementia.Item Adults Are Not Big Children: What Brain Magnetic Resonance Imaging Findings Tell Us About Differences in Pediatric and Adult Cerebral Malaria(Oxford, 2020-12) John, Chandy C.; Pediatrics, School of MedicineItem Altered bile acid profile in mild cognitive impairment and Alzheimer's disease: Relationship to neuroimaging and CSF biomarkers(Elsevier, 2019-02) Nho, Kwangsik; Kueider-Paisley, Alexandra; MahmoudianDehkordi, Siamak; Arnold, Matthias; Risacher, Shannon L.; Louie, Gregory; Blach, Colette; Baillie, Rebecca; Han, Xianlin; Kastenmüller, Gabi; Jia, Wei; Xie, Guoxiang; Ahmad, Shahzad; Hankemeier, Thomas; van Duijn, Cornelia M.; Trojanowski, John Q.; Shaw, Leslie M.; Weiner, Michael W.; Doraiswamy, P. Murali; Saykin, Andrew J.; Kaddurah-Daouk, Rima; Radiology and Imaging Sciences, School of MedicineINTRODUCTION: Bile acids (BAs) are the end products of cholesterol metabolism produced by human and gut microbiome co-metabolism. Recent evidence suggests gut microbiota influence pathological features of Alzheimer's disease (AD) including neuroinflammation and amyloid-β deposition. METHOD: Serum levels of 20 primary and secondary BA metabolites from the AD Neuroimaging Initiative (n = 1562) were measured using targeted metabolomic profiling. We assessed the association of BAs with the "A/T/N" (amyloid, tau, and neurodegeneration) biomarkers for AD: cerebrospinal fluid (CSF) biomarkers, atrophy (magnetic resonance imaging), and brain glucose metabolism ([18F]FDG PET). RESULTS: Of 23 BAs and relevant calculated ratios after quality control procedures, three BA signatures were associated with CSF Aβ1-42 ("A") and three with CSF p-tau181 ("T") (corrected P < .05). Furthermore, three, twelve, and fourteen BA signatures were associated with CSF t-tau, glucose metabolism, and atrophy ("N"), respectively (corrected P < .05). DISCUSSION: This is the first study to show serum-based BA metabolites are associated with "A/T/N" AD biomarkers, providing further support for a role of BA pathways in AD pathophysiology. Prospective clinical observations and validation in model systems are needed to assess causality and specific mechanisms underlying this association.Item Altered cerebellar-cortical resting-state functional connectivity in cannabis users(Sage, 2021) Schnakenberg Martin, Ashley M.; Kim, Dae-Jin; Newman, Sharlene D.; Cheng, Hu; Hetrick, William P.; Mackie, Ken; O’Donnell, Brian F.; Psychiatry, School of MedicineBackground: Cannabis use has been associated with abnormalities in cerebellar mediated motor and non-motor (i.e. cognition and personality) phenomena. Since the cerebellum is a region with high cannabinoid type 1 receptor density, these impairments may reflect alterations of signaling between the cerebellum and other brain regions. Aims: We hypothesized that cerebellar-cortical resting-state functional connectivity (rsFC) would be altered in cannabis users, relative to their non-using peers. It was also hypothesized that differences in rsFC would be associated with cannabis use features, such as age of initiation and lifetime use. Methods: Cerebellar-cortical and subcortical rsFCs were computed between 28 cerebellar lobules, defined by a spatially unbiased atlas template of the cerebellum, and individual voxels in the cerebral regions, in 41 regular cannabis users (20 female) and healthy non-using peers (N = 31; 18 female). We also investigated associations between rsFC and cannabis use features (e.g. lifetime cannabis use and age of initiation). Results: Cannabis users demonstrated hyperconnectivity between the anterior cerebellar regions (i.e. lobule I-IV) with the posterior cingulate cortex, and hypoconnectivity between the rest of the cerebellum (i.e. Crus I and II, lobule VIIb, VIIIa, VIIIb, IX, and X) and the cortex. No associations were observed between features of cannabis use and rsFC. Conclusions: Cannabis use was associated with altered patterns of rsFC from the cerebellum to the cerebral cortex which may have a downstream impact on behavior and cognition.Item Application of 23Na MRI to Monitor Chemotherapeutic Response in RIF-1 Tumors(Elsevier, 2005-07) Babsky, Andriy M.; Hekmatyar, Shahryar K.; Zhang, Hong; Radiology and Imaging Sciences, School of MedicineEffects of an alkylating anticancer drug, cyclophosphamide (Cp), on 23Na signal intensity (23Na SI) and water apparent diffusion coefficient (ADC) were examined in subcutaneously - implanted radiation-induced fibrosarcoma (RIF-1) tumors by in vivo23Na and 1H magnetic resonance imaging (MRI). MRI experiments were performed on untreated control (n = 5) and Cp-treated (n = 6) C3H mice, once before Cp injection (300 mg/kg) then daily for 3 days after treatment. Tumor volumes were significantly lower in treated animals 2 and 3 days posttreatment. At the same time points, MRI experiments showed an increase in both 23Na SI and water ADC in treated tumors, whereas control tumors did not show any significant changes. The correlation between 23Na SI and water ADC changes was dramatically increased in the Cp-treated group, suggesting that the observed increases in 23Na SI and water ADC were caused by the same mechanism. Histologic sections showed decreased cell density in the regions of increased 23Na and water ADC SI. Destructive chemical analysis showed that Cp treatment increased the relative extracellular space and tumor [Na+]. We conclude that the changes in water ADC and 23Na SI were largely due to an increase in extracellular space. 23Na MRI and 1H water ADC measurements may provide valuable noninvasive techniques for monitoring chemotherapeutic responses.