The differential proteomic response to ischemic stroke in appalachian subjects treated with mechanical thrombectomy.

INTRODUCTION: The Appalachia region of North America is known to have significant health disparities, specifically, worse risk factors and outcomes for stroke. Appalachians are more likely to have comorbidities related to stroke, such as diabetes, obesity, and tobacco use, and are often less likely to have stroke interventions, such as mechanical thrombectomy (MT), for emergent large vessel occlusion (ELVO). As our Comprehensive Stroke Center directly serves stroke subjects from both Appalachian and non-Appalachian areas, inflammatory proteomic biomarkers were identified associated with stroke outcomes specific to subjects residing in Appalachia. METHODS: There were 81 subjects that met inclusion criteria for this study. These subjects underwent MT for ELVO, and carotid arterial blood samples acquired at time of intervention were sent for proteomic analysis. Samples were processed in accordance with the Blood And Clot Thrombectomy Registry And Collaboration (BACTRAC; clinicaltrials.gov; NCT03153683). Statistical analyses were utilized to examine whether relationships between protein expression and outcomes differed by Appalachian status for functional (NIH Stroke Scale; NIHSS and Modified Rankin Score; mRS), and cognitive outcomes (Montreal Cognitive Assessment; MoCA). RESULTS: No significant differences were found in demographic data or co-morbidities when comparing Appalachian to non-Appalachian subjects. However, time from stroke onset to treatment (last known normal) was significantly longer and edema volume significantly higher in patients from Appalachia. Further, when comparing Appalachian to non-Appalachian subjects, there were significant unadjusted differences in the NIHSS functional outcome. A comprehensive analysis of 184 proteins from Olink proteomic (92 Cardiometabolic and 92 Inflammation panels) showed that the association between protein expression outcomes significantly differed by Appalachian status for seven proteins for the NIHSS, two proteins for the MoCA, and three for the mRS. CONCLUSION: Our study utilizes an ELVO tissue bank and registry to investigate the intracranial/intravascular proteomic environment occurring at the time of thrombectomy. We found that patients presenting from Appalachian areas have different levels of proteomic expression at the time of MT when compared to patients presenting from non-Appalachian areas. These proteins differentially relate to stroke outcome and could be used as prognostic biomarkers, or as targets for novel therapies. The identification of a disparate proteomic response in Appalachian patients provides initial insight to the biological basis for health disparity. Nevertheless, further investigations through community-based studies are imperative to elucidate the underlying causes of this differential response.

Regenerating Family Member 3 Alpha Is Predictive of Mortality Following Emergent Large Vessel Occlusion.

Regenerating Family Member 3 Alpha (REG3A) is an antimicrobial protein secreted by the intestine and pancreas with additional immunomodulatory properties. Previously, we published that REG3A expression in ischemic stroke patient systemic blood, during mechanical thrombectomy (MT), is significantly associated with inflammatory cytokines and patient function on admission. This paper, however, did not investigate post-acute death rates. Therefore, we investigated plasma REG3A protein expression, during MT, in patients (n = 141) that survived or died within the end of the follow-up after MT. Subjects who died had significantly higher systemic plasma REG3A levels at the time of MT compared to survivors (p = 0.001). Age, sex, time from last known normal, and admission NIHSS were included as predictors to control for confounding variables and were all examined to determine their association in patient mortality. Logistic regression was used to demonstrate that higher odds of death were associated with increased REG3A levels (p = 0.002). REG3A demonstrated acceptable discrimination (AUC (95% CI): 0.669 (0.566-0.772) in predicting mortality. The overall model with age, sex, time from last known normal, and admission NIHSS discriminated well between survivors and those who died (AUC (95% CI): 0.784 (0.703-0.864)). In conclusion, REG3A could be promising as a biomarker to prognosticate stroke outcomes and stratify high-risk groups following acute ischemic stroke.

Inflammatory-associated proteomic predictors of cognitive outcome in subjects with ELVO treated by mechanical thrombectomy.

BACKGROUND: Emergent Large Vessel Occlusion (ELVO) stroke causes devastating vascular events which can lead to significant cognitive decline and dementia. In the subset of ELVO subjects treated with mechanical thrombectomy (MT) at our institution, we aimed to identify systemic and intracranial proteins predictive of cognitive function at time of discharge and at 90-days. These proteomic biomarkers may serve as prognostic indicators of recovery, as well as potential targets for novel/existing therapeutics to be delivered during the subacute stage of stroke recovery. METHODS: At the University of Kentucky Center for Advanced Translational Stroke Sciences, the BACTRAC tissue registry (clinicaltrials.gov; NCT03153683) of human biospecimens acquired during ELVO stroke by MT is utilized for research. Clinical data are collected on each enrolled subject who meets inclusion criteria. Blood samples obtained during thrombectomy were sent to Olink Proteomics for proteomic expression values. Montreal Cognitive Assessments (MoCA) were evaluated with categorical variables using ANOVA and t-tests, and continuous variables using Pearson correlations. RESULTS: There were n = 52 subjects with discharge MoCA scores and n = 28 subjects with 90-day MoCA scores. Several systemic and intracranial proteins were identified as having significant correlations to discharge MoCA scores as well as 90-day MoCA scores. Highlighted proteins included s-DPP4, CCL11, IGFBP3, DNER, NRP1, MCP1, and COMP. CONCLUSION: We set out to identify proteomic predictors and potential therapeutic targets related to cognitive outcomes in ELVO subjects undergoing MT. Here, we identify several proteins which predicted MoCA after MT, which may serve as therapeutic targets to lessen post-stroke cognitive decline.

T1 and T2 MR fingerprinting measurements of prostate cancer and prostatitis correlate with deep learning-derived estimates of epithelium, lumen, and stromal composition on corresponding whole mount histopathology.

OBJECTIVES: To explore the associations between T1 and T2 magnetic resonance fingerprinting (MRF) measurements and corresponding tissue compartment ratios (TCRs) on whole mount histopathology of prostate cancer (PCa) and prostatitis. MATERIALS AND METHODS: A retrospective, IRB-approved, HIPAA-compliant cohort consisting of 14 PCa patients who underwent 3 T multiparametric MRI along with T1 and T2 MRF maps prior to radical prostatectomy was used. Correspondences between whole mount specimens and MRI and MRF were manually established. Prostatitis, PCa, and normal peripheral zone (PZ) regions of interest (ROIs) on pathology were segmented for TCRs of epithelium, lumen, and stroma using two U-net deep learning models. Corresponding ROIs were mapped to T2-weighted MRI (T2w), apparent diffusion coefficient (ADC), and T1 and T2 MRF maps. Their correlations with TCRs were computed using Pearson's correlation coefficient (R). Statistically significant differences in means were assessed using one-way ANOVA. RESULTS: Statistically significant differences (p < 0.01) in means of TCRs and T1 and T2 MRF were observed between PCa, prostatitis, and normal PZ. A negative correlation was observed between T1 and T2 MRF and epithelium (R = - 0.38, - 0.44, p < 0.05) of PCa. T1 MRF was correlated in opposite directions with stroma of PCa and prostatitis (R = 0.35, - 0.44, p < 0.05). T2 MRF was positively correlated with lumen of PCa and prostatitis (R = 0.57, 0.46, p < 0.01). Mean T2 MRF showed significant differences (p < 0.01) between PCa and prostatitis across both transition zone (TZ) and PZ, while mean T1 MRF was significant (p = 0.02) in TZ. CONCLUSION: Significant associations between MRF (T1 in the TZ and T2 in the PZ) and tissue compartments on corresponding histopathology were observed. KEY POINTS: • Mean T2 MRF measurements and ADC within cancerous regions of interest dropped with increasing ISUP prognostic groups (IPG). • Mean T1 and T2 MRF measurements were significantly different (p < 0.001) across IPGs, prostatitis, and normal peripheral zone (NPZ). • T2 MRF showed stronger correlations in the peripheral zone, while T1 MRF showed stronger correlations in the transition zone with histopathology for prostate cancer.

Simultaneous Mapping of T1 and T2 Using Cardiac Magnetic Resonance Fingerprinting in a Cohort of Healthy Subjects at 1.5T.

BACKGROUND: Cardiac MR fingerprinting (cMRF) is a novel technique for simultaneous T1 and T2 mapping. PURPOSE: To compare T1 /T2 measurements, repeatability, and map quality between cMRF and standard mapping techniques in healthy subjects. STUDY TYPE: Prospective. POPULATION: In all, 58 subjects (ages 18-60). FIELD STRENGTH/SEQUENCE: cMRF, modified Look-Locker inversion recovery (MOLLI), and T2 -prepared balanced steady-state free precession (bSSFP) at 1.5T. ASSESSMENT: T1 /T2 values were measured in 16 myocardial segments at apical, medial, and basal slice positions. Test-retest and intrareader repeatability were assessed for the medial slice. cMRF and conventional mapping sequences were compared using ordinal and two alternative forced choice (2AFC) ratings. STATISTICAL TESTS: Paired t-tests, Bland-Altman analyses, intraclass correlation coefficient (ICC), linear regression, one-way analysis of variance (ANOVA), and binomial tests. RESULTS: Average T1 measurements were: basal 1007.4±96.5 msec (cMRF), 990.0±45.3 msec (MOLLI); medial 995.0±101.7 msec (cMRF), 995.6±59.7 msec (MOLLI); apical 1006.6±111.2 msec (cMRF); and 981.6±87.6 msec (MOLLI). Average T2 measurements were: basal 40.9±7.0 msec (cMRF), 46.1±3.5 msec (bSSFP); medial 41.0±6.4 msec (cMRF), 47.4±4.1 msec (bSSFP); apical 43.5±6.7 msec (cMRF), 48.0±4.0 msec (bSSFP). A statistically significant bias (cMRF T1 larger than MOLLI T1 ) was observed in basal (17.4 msec) and apical (25.0 msec) slices. For T2 , a statistically significant bias (cMRF lower than bSSFP) was observed for basal (-5.2 msec), medial (-6.3 msec), and apical (-4.5 msec) slices. Precision was lower for cMRF-the average of the standard deviation measured within each slice was 102 msec for cMRF vs. 61 msec for MOLLI T1 , and 6.4 msec for cMRF vs. 4.0 msec for bSSFP T2 . cMRF and conventional techniques had similar test-retest repeatability as quantified by ICC (0.87 cMRF vs. 0.84 MOLLI for T1 ; 0.85 cMRF vs. 0.85 bSSFP for T2 ). In the ordinal image quality comparison, cMRF maps scored higher than conventional sequences for both T1 (all five features) and T2 (four features). DATA CONCLUSION: This work reports on myocardial T1 /T2 measurements in healthy subjects using cMRF and standard mapping sequences. cMRF had slightly lower precision, similar test-retest and intrareader repeatability, and higher scores for map quality. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 1 J. Magn. Reson. Imaging 2020;52:1044-1052.

Three-dimensional MR Fingerprinting for Quantitative Breast Imaging.

Purpose To develop a fast three-dimensional method for simultaneous T1 and T2 quantification for breast imaging by using MR fingerprinting. Materials and Methods In this prospective study, variable flip angles and magnetization preparation modules were applied to acquire MR fingerprinting data for each partition of a three-dimensional data set. A fast postprocessing method was implemented by using singular value decomposition. The proposed technique was first validated in phantoms and then applied to 15 healthy female participants (mean age, 24.2 years ± 5.1 [standard deviation]; range, 18-35 years) and 14 female participants with breast cancer (mean age, 55.4 years ± 8.8; range, 39-66 years) between March 2016 and April 2018. The sensitivity of the method to B1 field inhomogeneity was also evaluated by using the Bloch-Siegert method. Results Phantom results showed that accurate and volumetric T1 and T2 quantification was achieved by using the proposed technique. The acquisition time for three-dimensional quantitative maps with a spatial resolution of 1.6 × 1.6 × 3 mm3 was approximately 6 minutes. For healthy participants, averaged T1 and T2 relaxation times for fibroglandular tissues at 3.0 T were 1256 msec ± 171 and 46 msec ± 7, respectively. Compared with normal breast tissues, higher T2 relaxation time (68 msec ± 13) was observed in invasive ductal carcinoma (P < .001), whereas no statistical difference was found in T1 relaxation time (1183 msec ± 256; P = .37). Conclusion A method was developed for breast imaging by using the MR fingerprinting technique, which allows simultaneous and volumetric quantification of T1 and T2 relaxation times for breast tissues. © RSNA, 2018 Online supplemental material is available for this article.

Radiomic features on MRI enable risk categorization of prostate cancer patients on active surveillance: Preliminary findings.

BACKGROUND: Radiomic analysis is defined as computationally extracting features from radiographic images for quantitatively characterizing disease patterns. There has been recent interest in examining the use of MRI for identifying prostate cancer (PCa) aggressiveness in patients on active surveillance (AS). PURPOSE: To evaluate the performance of MRI-based radiomic features in identifying the presence or absence of clinically significant PCa in AS patients. STUDY TYPE: Retrospective. SUBJECTS MODEL: MRI/TRUS (transperineal grid ultrasound) fusion-guided biopsy was performed for 56 PCa patients on AS who had undergone prebiopsy. FIELD STRENGTH/SEQUENCE: 3T, T2 -weighted (T2 w) and diffusion-weighted (DW) MRI. ASSESSMENT: A pathologist histopathologically defined the presence of clinically significant disease. A radiologist manually delineated lesions on T2 w-MRs. Then three radiologists assessed MRIs using PIRADS v2.0 guidelines. Tumors were categorized into four groups: MRI-negative-biopsy-negative (Group 1, N = 15), MRI-positive-biopsy-positive (Group 2, N = 16), MRI-negative-biopsy-positive (Group 3, N = 10), and MRI-positive-biopsy-negative (Group 4, N = 15). In all, 308 radiomic features (First-order statistics, Gabor, Laws Energy, and Haralick) were extracted from within the annotated lesions on T2 w images and apparent diffusion coefficient (ADC) maps. The top 10 features associated with clinically significant tumors were identified using minimum-redundancy-maximum-relevance and used to construct three machine-learning models that were independently evaluated for their ability to identify the presence and absence of clinically significant disease. STATISTICAL TESTS: Wilcoxon rank-sum tests with P < 0.05 considered statistically significant. RESULTS: Seven T2 w-based (First-order Statistics, Haralick, Laws, and Gabor) and three ADC-based radiomic features (Laws, Gradient and Sobel) exhibited statistically significant differences (P < 0.001) between malignant and normal regions in the training groups. The three constructed models yielded overall accuracy improvement of 33, 60, 80% and 30, 40, 60% for patients in testing groups, when compared to PIRADS v2.0 alone. DATA CONCLUSION: Radiomic features could help in identifying the presence and absence of clinically significant disease in AS patients when PIRADS v2.0 assessment on MRI contradicted pathology findings of MRI-TRUS prostate biopsies. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018.

Cost-effectiveness of MR Imaging-guided Strategies for Detection of Prostate Cancer in Biopsy-Naive Men.

Purpose To evaluate the cost-effectiveness of multiparametric diagnostic magnetic resonance (MR) imaging examination followed by MR imaging-guided biopsy strategies in the detection of prostate cancer in biopsy-naive men presenting with clinical suspicion of cancer for the first time. Materials and Methods A decision-analysis model was created for biopsy-naive men who had been recommended for prostate biopsy on the basis of abnormal digital rectal examination results or elevated prostate-specific antigen levels (age groups: 41-50 years, 51-60 years, and 61-70 years). The following three major strategies were evaluated: (a) standard transrectal ultrasonography (US)-guided biopsy; (b) diagnostic MR imaging followed by MR imaging-targeted biopsy, with no biopsy performed if MR imaging findings were negative; and (c) diagnostic MR imaging followed by MR imaging-targeted biopsy, with a standard biopsy performed when MR imaging findings were negative. The following three MR imaging-guided biopsy strategies were further evaluated in each MR imaging category: (a) biopsy with cognitive guidance, (b) biopsy with MR imaging/US fusion guidance, and (c) in-gantry MR imaging-guided biopsy. Model parameters were derived from the literature. The primary outcome measure was net health benefit (NHB), which was measured as quality-adjusted life-years (QALYs) gained or lost by investing resources in a new strategy compared with a standard strategy at a willingness-to-pay (WTP) threshold of $50 000 per QALY gained. Probabilistic sensitivity analysis was performed by using Monte Carlo simulations. Results Noncontrast MR imaging followed by cognitively guided MR biopsy (no standard biopsy if MR imaging findings were negative) was the most cost-effective approach, yielding an additional NHB of 0.198 QALY compared with the standard biopsy approach. Noncontrast MR imaging followed by in-gantry MR imaging-guided biopsy (no standard biopsy if MR imaging findings were negative) led to the highest NHB gain of 0.251 additional QALY compared with the standard biopsy strategy. All MR imaging strategies were cost-effective in 94.05% of Monte Carlo simulations. Analysis by age groups yielded similar results. Conclusion MR imaging-guided strategies for the detection of prostate cancer were cost-effective compared with the standard biopsy strategy in a decision-analysis model. © RSNA, 2017 Online supplemental material is available for this article.

Development of a Combined MR Fingerprinting and Diffusion Examination for Prostate Cancer.

Purpose To develop and evaluate an examination consisting of magnetic resonance (MR) fingerprinting-based T1, T2, and standard apparent diffusion coefficient (ADC) mapping for multiparametric characterization of prostate disease. Materials and Methods This institutional review board-approved, HIPAA-compliant retrospective study of prospectively collected data included 140 patients suspected of having prostate cancer. T1 and T2 mapping was performed with fast imaging with steady-state precession-based MR fingerprinting with ADC mapping. Regions of interest were drawn by two independent readers in peripheral zone lesions and normal-appearing peripheral zone (NPZ) tissue identified on clinical images. T1, T2, and ADC were recorded for each region. Histopathologic correlation was based on systematic transrectal biopsy or cognitively targeted biopsy results, if available. Generalized estimating equations logistic regression was used to assess T1, T2, and ADC in the differentiation of (a) cancer versus NPZ, (b) cancer versus prostatitis, (c) prostatitis versus NPZ, and (d) high- or intermediate-grade tumors versus low-grade tumors. Analysis was performed for all lesions and repeated in a targeted biopsy subset. Discriminating ability was evaluated by using the area under the receiver operating characteristic curve (AUC). Results In this study, 109 lesions were analyzed, including 39 with cognitively targeted sampling. T1, T2, and ADC from cancer (mean, 1628 msec ± 344, 73 msec ± 27, and 0.773 × 10-3 mm2/sec ± 0.331, respectively) were significantly lower than those from NPZ (mean, 2247 msec ± 450, 169 msec ± 61, and 1.711 × 10-3 mm2/sec ± 0.269) (P < .0001 for each) and together produced the best separation between these groups (AUC = 0.99). ADC and T2 together produced the highest AUC of 0.83 for separating high- or intermediate-grade tumors from low-grade cancers. T1, T2, and ADC in prostatitis (mean, 1707 msec ± 377, 79 msec ± 37, and 0.911 × 10-3 mm2/sec ± 0.239) were significantly lower than those in NPZ (P < .0005 for each). Interreader agreement was excellent, with an intraclass correlation coefficient greater than 0.75 for both T1 and T2 measurements. Conclusion This study describes the development of a rapid MR fingerprinting- and diffusion-based examination for quantitative characterization of prostatic tissue. © RSNA, 2017 Online supplemental material is available for this article.

Slice profile and B1 corrections in 2D magnetic resonance fingerprinting.

PURPOSE: The goal of this study is to characterize and improve the accuracy of 2D magnetic resonance fingerprinting (MRF) scans in the presence of slice profile (SP) and B1 imperfections, which are two main factors that affect quantitative results in MRF. METHODS: The SP and B1 imperfections are characterized and corrected separately. The SP effect is corrected by simulating the radiofrequency pulse in the dictionary, and the B1 is corrected by acquiring a B1 map using the Bloch-Siegert method before each scan. The accuracy, precision, and repeatability of the proposed method are evaluated in phantom studies. The effects of both SP and B1 imperfections are also illustrated and corrected in the in vivo studies. RESULTS: The SP and B1 corrections improve the accuracy of the T1 and T2 values, independent of the shape of the radiofrequency pulse. The T1 and T2 values obtained from different excitation patterns become more consistent after corrections, which leads to an improvement of the robustness of the MRF design. CONCLUSION: This study demonstrates that MRF is sensitive to both SP and B1 effects, and that corrections can be made to improve the accuracy of MRF with only a 2-s increase in acquisition time. Magn Reson Med 78:1781-1789, 2017. © 2017 International Society for Magnetic Resonance in Medicine.

Radiomic features for prostate cancer detection on MRI differ between the transition and peripheral zones: Preliminary findings from a multi-institutional study.

PURPOSE: To evaluate in a multi-institutional study whether radiomic features useful for prostate cancer (PCa) detection from 3 Tesla (T) multi-parametric MRI (mpMRI) in the transition zone (TZ) differ from those in the peripheral zone (PZ). MATERIALS AND METHODS: 3T mpMRI, including T2-weighted (T2w), apparent diffusion coefficient (ADC) maps, and dynamic contrast-enhanced MRI (DCE-MRI), were retrospectively obtained from 80 patients at three institutions. This study was approved by the institutional review board of each participating institution. First-order statistical, co-occurrence, and wavelet features were extracted from T2w MRI and ADC maps, and contrast kinetic features were extracted from DCE-MRI. Feature selection was performed to identify 10 features for PCa detection in the TZ and PZ, respectively. Two logistic regression classifiers used these features to detect PCa and were evaluated by area under the receiver-operating characteristic curve (AUC). Classifier performance was compared with a zone-ignorant classifier. RESULTS: Radiomic features that were identified as useful for PCa detection differed between TZ and PZ. When classification was performed on a per-voxel basis, a PZ-specific classifier detected PZ tumors on an independent test set with significantly higher accuracy (AUC = 0.61-0.71) than a zone-ignorant classifier trained to detect cancer throughout the entire prostate (P < 0.05). When classifiers were evaluated on MRI data from multiple institutions, statistically similar AUC values (P > 0.14) were obtained for all institutions. CONCLUSION: A zone-aware classifier significantly improves the accuracy of cancer detection in the PZ. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 2 J. MAGN. RESON. IMAGING 2017;46:184-193.

MR Fingerprinting for Rapid Quantitative Abdominal Imaging.

PURPOSE: To develop a magnetic resonance (MR) "fingerprinting" technique for quantitative abdominal imaging. MATERIALS AND METHODS: This HIPAA-compliant study had institutional review board approval, and informed consent was obtained from all subjects. To achieve accurate quantification in the presence of marked B0 and B1 field inhomogeneities, the MR fingerprinting framework was extended by using a two-dimensional fast imaging with steady-state free precession, or FISP, acquisition and a Bloch-Siegert B1 mapping method. The accuracy of the proposed technique was validated by using agarose phantoms. Quantitative measurements were performed in eight asymptomatic subjects and in six patients with 20 focal liver lesions. A two-tailed Student t test was used to compare the T1 and T2 results in metastatic adenocarcinoma with those in surrounding liver parenchyma and healthy subjects. RESULTS: Phantom experiments showed good agreement with standard methods in T1 and T2 after B1 correction. In vivo studies demonstrated that quantitative T1, T2, and B1 maps can be acquired within a breath hold of approximately 19 seconds. T1 and T2 measurements were compatible with those in the literature. Representative values included the following: liver, 745 msec ± 65 (standard deviation) and 31 msec ± 6; renal medulla, 1702 msec ± 205 and 60 msec ± 21; renal cortex, 1314 msec ± 77 and 47 msec ± 10; spleen, 1232 msec ± 92 and 60 msec ± 19; skeletal muscle, 1100 msec ± 59 and 44 msec ± 9; and fat, 253 msec ± 42 and 77 msec ± 16, respectively. T1 and T2 in metastatic adenocarcinoma were 1673 msec ± 331 and 43 msec ± 13, respectively, significantly different from surrounding liver parenchyma relaxation times of 840 msec ± 113 and 28 msec ± 3 (P < .0001 and P < .01) and those in hepatic parenchyma in healthy volunteers (745 msec ± 65 and 31 msec ± 6, P < .0001 and P = .021, respectively). CONCLUSION: A rapid technique for quantitative abdominal imaging was developed that allows simultaneous quantification of multiple tissue properties within one 19-second breath hold, with measurements comparable to those in published literature.

Pearls & Oy-sters: Bibrachial Amyotrophy From a Dural Tear.

Bibrachial amyotrophy signifies a clinical phenotype characterized by weakness in both upper extremities with preserved strength in the face, neck, and lower extremities. The underlying causes of bibrachial amyotrophy are broad. We report a patient exhibiting bibrachial amyotrophy who initially received a diagnosis of amyotrophic lateral sclerosis (ALS); however, his clinical course and NCS/EMG were atypical for ALS. Further evaluation demonstrated dural tears with CSF leak, resulting in a compressive extradural fluid collection, ventral myelopathy, and intracranial hypotension. Dural tear and ALS have overlapping features, including the manifestation of the bibrachial amyotrophy phenotype and the presence of T2 hyperintensities in the anterior horn cells, recognized by an "owl's eye" appearance on spine MRI. Clinical and radiologic vigilance is required to identify rare cases of dural tear causing ventral myelopathy that manifest as bibrachial amyotrophy.

Now that the door is open: an update on ischemic stroke pharmacotherapeutics for the neurointerventionalist.

The last 10 years have seen a major shift in management of large vessel ischemic stroke with changes towards ever-expanding use of reperfusion therapies (intravenous thrombolysis and mechanical thrombectomy). These strategies 'open the door' to acute therapeutics for ischemic tissue, and we should investigate novel therapeutic approaches to enhance survival of recently reperfused brain. Key insights into new approaches have been provided through translational research models and preclinical paradigms, and through detailed research on ischemic mechanisms. Additional recent clinical trials offer exciting salvos into this new strategy of pairing reperfusion with neuroprotective therapy. This pairing strategy can be employed using drugs that have shown neuroprotective efficacy; neurointerventionalists can administer these during or immediately after reperfusion therapy. This represents a crucial moment when we emphasize reperfusion, and have the technological capability along with the clinical trial experience to lead the way in multiprong approaches to stroke treatment.

Plasma protein alterations during human large vessel stroke: A controlled comparison study.

BACKGROUND: Stroke is a major cause of death and disability in the United States. Mechanical thrombectomy (MT) and tissue plasminogen activator are the current treatments for ischemic stroke, which have improved clinical outcomes. Despite these treatments, functional and cognitive deficits still occur demonstrating a need for predictive biomarkers for beneficial clinical outcomes which can be used as therapeutic targets for pharmacotherapy. The aim of this study compares the proteomic expression of systemic arterial blood collected at the time of MT to those from a matched cerebrovascular disease (CVD) control cohort. METHODS: The Blood And Clot Thrombectomy Registry And Collaboration (BACTRAC) (clinicaltrials.gov NCT03153683) collects and banks arterial blood, both distal and proximal to the thrombus, from ischemic stroke subjects undergoing MT. Arterial blood from patients undergoing a diagnostic angiogram was also collected and banked as CVD controls. Changes in cardiometabolic and inflammatory proteins between stroke and CVD controls were analyzed via Olink Proteomics. RESULTS: Proteins including ARTN, TWEAK, HGF, CCL28, FGF-5, CXCL9, TRANCE and GDNF were found to be decreased in stroke subjects when compared to CVD controls. CXCL1, CCL5, OSM, GP1BA, IL6, MMP-1, and CXCL5 were increased in stroke subjects when compared to CVD controls. These proteins were also significantly correlated to stroke outcome metrics such as NIHSS, infarct volume and MoCA scoring. CONCLUSION: Overall, acute stroke patients had an increase in inflammatory proteins with a decrease in trophic proteins systemically compared to matched CVD controls. Using our CVD controls, proteins of interest were directly compared to stroke patients with the same cerebrovascular risk factors instead of statistically controlling for comorbidities. The novel methodology of matching an arterial blood CVD control group to a stroke group, as well as controlling for age and comorbid status add to the literature on prognostic stroke biomarkers, which are specific targets for future therapeutics.

Alterations in Local Peri-Infarct Blood Gases in Stroke Patients Undergoing Thrombectomy.

BACKGROUND: Ischemic stroke is a prevalent, devastating disease with high morbidity and mortality. Despite extensive research using animal models, significant gaps remain in understanding the pathological processes in human stroke. We previously developed a tissue bank to analyze the blood immediately proximal and distal to an intracranial thrombus in patients undergoing mechanical thrombectomy (ClinicalTrials.gov identifier, NCT03153683). Our goal for the present project was to evaluate the blood gas changes and acid/base balance during stroke and determine how vascular collateralization affects these changes. METHODS: We analyzed the blood samples and computed tomography angiography collateral scores from the first 62 patients in the BACTRAC (Blood and Clot Thrombectomy Registry and Collaboration) registry. The bicarbonate, partial pressure of oxygen, and partial pressure of carbon dioxide (pCO2) values of the intracranial (distal) and systemic (proximal) arterial blood relative to the occlusive thrombus were analyzed. Analysis of the group differences in systemic and intracranial blood gas values was also performed. RESULTS: The partial pressure of oxygen, pCO2, and bicarbonate levels were all significantly higher in the systemic blood than in the intracranial blood (P < 0.001 for all) at thrombectomy. Collateralization did not significantly affect the distal blood gas values. Compared with the female patients, the male patients had had higher systemic pCO2 values (39.8 vs. 36.6 mm Hg; P = 0.0065) and lower systemic and intracranial pH values (7.351 vs. 7.392; P = 0.0047). CONCLUSIONS: The arterial blood gases differed immediately proximal and distal to thrombi in large vessel occlusive stroke. Although vascular collateralization did not appear to affect the blood gas changes, some blood gas values differed between men and women. The changes in bicarbonate and pCO2 suggested a compensatory acid-base process occurring at the time of infarction.

Influence of BMI on adenosine deaminase and stroke outcomes in mechanical thrombectomy subjects.

BACKGROUND: Emergent Large Vessel Occlusion (ELVO) strokes are ischemic vascular events for which novel biomarkers and therapies are needed. The purpose of this study is to investigate the role of Body Mass Index (BMI) on protein expression and signaling at the time of ELVO intervention. Additionally, we highlight the protein adenosine deaminase (ADA), which is a deaminating enzyme that degrades adenosine, which has been shown to be neuroprotective in ischemia. We investigate the relationship between ADA and BMI, stroke outcomes, and associated proteomic networks which might aid in personalizing prognosis and future treatment of ELVO stroke. METHODS: The Blood And Clot Thrombectomy And Collaboration (BACTRAC) study is a continually enrolling tissue bank (clinicaltrials.gov NCT03153683) and registry from stroke patients undergoing mechanical thrombectomy (MT). N â€‹= â€‹61 human carotid plasma samples were analyzed for inflammatory and cardiometabolic protein expression by Olink Proteomics. Statistical analyses used t-tests, linear, logistic, and robust regressions, to assess the relationship between BMI, proteomic expression, and stroke-related outcomes. RESULTS: The 61 subjects studied were broken into three categories: normal weight (BMI 18.5-24.9) which contained 19 subjects, overweight (BMI 25-30) which contained 25 subjects, and obese (BMI ≥30) which contained 17 subjects. Normal BMI group was a significantly older population (mean 76 years) when compared to overweight (mean 66 years) and obese (mean 61 years) with significance of p â€‹= â€‹0.041 and p â€‹= â€‹0.005, respectively. When compared to normal weight and overweight categories, the obese category had significantly higher levels of adenosine deaminase (ADA) expression (p â€‹= â€‹0.01 and p â€‹= â€‹0.039, respectively). Elevated levels of ADA were found to have a significant positive correlation with both infarct volume and edema volume (p â€‹= â€‹0.013 and p â€‹= â€‹0.041, respectively), and were associated with a more severe stroke (NIHSS on discharge) and greater stroke related disability (mRS on discharge) with significance of p â€‹= â€‹0.053 and p â€‹= â€‹0.032, respectively. CONCLUSIONS: When examined according to BMI, subjects undergoing MT for ELVO demonstrate significant differences in the expression of certain plasma proteins, including ADA. Levels of ADA were found to be significantly higher in the obese population when compared to normal or overweight groups. Increased levels of ADA in the obese group were predictive of increased infarct volume, edema volume, and worse NIHSS scores and mRS at discharge. These data provide novel biomarker candidates as well as treatment targets while increasing the personalization of stroke prognosis and treatment.

Relationship between Mammographic Findings and Breast Abnormalities in a Nigerian Population.

PURPOSE: This study aims to describe the mammographic findings in a population of Nigerian women and to explore the relationships between abnormal mammographic findings, breast malignancy, and breast composition. METHODOLOGY: This was a retrospective study of consecutive mammograms carried out at Union Diagnostics and Clinical Services in Lagos, Nigeria from 2016 to 2018. Demographic information, indications for and findings on mammographic evaluation were obtained. A logistic regression fit model was used to establish the correlation between mammographic findings, breast density, and suspicion for breast malignancy (higher BIRADS scores). P ≤ 0.05 represented a statistically significant result. RESULTS: A total of 304 patients were involved in this study (age range 20-80 years, mean age 49.0 ± 10.5 years). The patients between 40 and 49 years formed the largest age group with 128 patients (42.4%). Most patients were referred for a breast mass/lump (115/304-38.6%); 56 patients (18.8%) presenting for routine screening. The most common finding on the mammograms was BIRADS 4 in both breasts in 96 patients (31.6%). Most patients had heterogeneous breast density (195 patients - 64.1%). Multivariate logistic regression analysis showed a significant correlation between history of mass, poorly defined margins, and suspicion of malignancy. There was no statistically significant association between abnormal mammographic findings and higher breast density. CONCLUSION: Poorly defined margins were positively correlated with BIRADS ratings suspicious for malignancy. The presence of a breast mass was positively correlated with a higher BIRADS score when other possible cofounding variables were not accounted for. Patient age did not correlate with breast density in this study.