Dr. Pulli is a dual fellowship trained diagnostic and interventional neuroradiologist with a focus on vascular disorders of the brain, head, neck, and spine. He is a clinical assistant professor in the Department of Radiology, Neuroradiology Division.

Having grown up in Austria, Dr. Pulli moved to the US after completing medical school in Innsbruck, Austria. He completed post-doctoral research training in stroke imaging in the Division of Neuroradiology at the Massachusetts General Hospital, as well as in experimental molecular imaging techniques of neuroinflammatory disorders at the Center for Systems Biology of Massachusetts General Hospital and Harvard Medical School.

He completed residency training in Radiology and fellowship training in Diagnostic Neuroradiology at the Massachusetts General Hospital in Boston. He then completed a second fellowship in interventional neuroradiology/neurointerventional surgery at Stanford University School of Medicine.

After having graduated from fellowship, Dr. Pulli then spent more than a year practicing Interventional Neuroradiology at Pacific Neuroscience Institute in Los Angeles. He employs state-of-the-art minimally invasive endovascular and percutaneous surgical techniques to treat patients with brain aneurysms, arteriovenous malformations, dural arteriovenous fistulas, carotid artery stenosis, acute stroke, chronic subdural hematoma, idiopathic intracranial hypertension, vascular tumors, and chronic back pain.

His research focuses on advanced imaging techniques for acute ischemic stroke and other neurovascular diseases. He has authored more than 40 peer-reviewed publications and received scientific grants from institutions such as the Radiological Society of North America and the Ernst Schering Foundation. In addition, he has made invited presentations to his peers at meetings of organizations such as the American Society of Neuroradiology, Radiological Society of North American, European Congress of Radiology, and Western Neuroradiological Society.

He is a member of the Society of Neurointerventional Surgery.

Clinical Focus

  • Neurointerventional Surgery
  • Interventional Neuroradiology
  • Aneurysm, Brain
  • Intracranial Arteriovenous Malformations
  • Dural Arteriovenous Fistula
  • Carotid Stenosis
  • Acute Stroke
  • Thrombectomy
  • Embolization, Therapeutic
  • Intracranial Atheroscleroses
  • Hypertension, Idiopathic Intracranial
  • Chronic Subdural Hematoma
  • Neuroradiology

Academic Appointments

  • Clinical Assistant Professor, Radiology
  • Clinical Assistant Professor (By courtesy), Neurosurgery

Professional Education

  • Fellowship, Stanford University Interventional Neuroradiology Fellowship, CA (2021)
  • Board Certification: American Board of Radiology, Diagnostic Radiology (2019)
  • Fellowship: Massachusetts General Hospital Neuroradiology Fellowship (2019) MA
  • Residency: Massachusetts General Hospital Radiology Residency (2018) MA
  • Internship: MetroWest Medical Center Transitional Year (2014) MA
  • Medical Education: Medical University Innsbruck (2009) Austria

All Publications

  • Percutaneous Disc Biopsy versus Bone Biopsy for the Identification of Infectious Agents in Osteomyelitis/Discitis. Journal of vascular and interventional radiology : JVIR Zamarud, A., Kesten, J., Park, D. J., Pulli, B., Telischak, N. A., Dodd, R. L., Do, H. M., Marks, M. P., Heit, J. J. 2024


    To determine whether sampling of the disc or bone is more likely to yield positive tissue culture results in patients with vertebral discitis and osteomyelitis (VDO).Retrospective review was performed of consecutive patients who underwent vertebral disc or vertebral body biopsy at a single institution between February 2019 and May 2023. Inclusion criteria were age ≥18 years, presumed VDO on spinal magnetic resonance (MR) imaging, absence of paraspinal abscess, and technically successful percutaneous biopsy with fluoroscopic guidance. The primary outcome was a positive biopsy culture result, and secondary outcomes included complications such as nerve injury and segmental artery injury.Sixty-six patients met the inclusion criteria; 36 patients (55%) underwent disc biopsy, and 30 patients (45%) underwent bone biopsy. Six patients required a repeat biopsy for an initially negative culture result. No significant demographic, laboratory, antibiotic administration, or pain medication use differences were observed between the 2 groups. Patients who underwent bone biopsy were more likely to have a history of intravenous drug use (26.7%) compared with patients who underwent disc biopsy (5.5%; P = .017). Positive tissue culture results were observed in 41% of patients who underwent disc biopsy and 15% of patients who underwent bone biopsy (P = .016). No vessel or nerve injuries were detected after procedure in either group.Percutaneous disc biopsy is more likely to yield a positive tissue culture result than vertebral body biopsy in patients with VDO.

    View details for DOI 10.1016/j.jvir.2024.02.016

    View details for PubMedID 38613536

  • Random expert sampling for deep learning segmentation of acute ischemic stroke on non-contrast CT. Journal of neurointerventional surgery Ostmeier, S., Axelrod, B., Liu, Y., Yu, Y., Jiang, B., Yuen, N., Pulli, B., Verhaaren, B. F., Kaka, H., Wintermark, M., Michel, P., Mahammedi, A., Federau, C., Lansberg, M. G., Albers, G. W., Moseley, M. E., Zaharchuk, G., Heit, J. J. 2024


    Outlining acutely infarcted tissue on non-contrast CT is a challenging task for which human inter-reader agreement is limited. We explored two different methods for training a supervised deep learning algorithm: one that used a segmentation defined by majority vote among experts and another that trained randomly on separate individual expert segmentations.The data set consisted of 260 non-contrast CT studies in 233 patients with acute ischemic stroke recruited from the multicenter DEFUSE 3 (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke 3) trial. Additional external validation was performed using 33 patients with matched stroke onset times from the University Hospital Lausanne. A benchmark U-Net was trained on the reference annotations of three experienced neuroradiologists to segment ischemic brain tissue using majority vote and random expert sampling training schemes. The median of volume, overlap, and distance segmentation metrics were determined for agreement in lesion segmentations between (1) three experts, (2) the majority model and each expert, and (3) the random model and each expert. The two sided Wilcoxon signed rank test was used to compare performances (1) to 2) and (1) to (3). We further compared volumes with the 24 hour follow-up diffusion weighted imaging (DWI, final infarct core) and correlations with clinical outcome (modified Rankin Scale (mRS) at 90 days) with the Spearman method.The random model outperformed the inter-expert agreement ((1) to (2)) and the majority model ((1) to (3)) (dice 0.51±0.04 vs 0.36±0.05 (P<0.0001) vs 0.45±0.05 (P<0.0001)). The random model predicted volume correlated with clinical outcome (0.19, P<0.05), whereas the median expert volume and majority model volume did not. There was no significant difference when comparing the volume correlations between random model, median expert volume, and majority model to 24 hour follow-up DWI volume (P>0.05, n=51).The random model for ischemic injury delineation on non-contrast CT surpassed the inter-expert agreement ((1) to (2)) and the performance of the majority model ((1) to (3)). We showed that the random model volumetric measures of the model were consistent with 24 hour follow-up DWI.

    View details for DOI 10.1136/jnis-2023-021283

    View details for PubMedID 38302420

  • Intravenous Tenecteplase and Carotid Artery Stenting in a Young Adult With Fibromuscular Dysplasia and Carotid Dissection. Stroke Alfandy, F., Dugue, R., Pulli, B., George, P. M. 2023

    View details for DOI 10.1161/STROKEAHA.123.045026

    View details for PubMedID 38152960

  • Matched-pair analysis of patients with ischemic stroke undergoing thrombectomy using next-generation balloon guide catheters. Journal of neurointerventional surgery Kim, L. H., Choi, J., Zhou, J., Wolman, D., Pendharkar, A. V., Lansberg, M. G., Albers, G. W., Dodd, R., Do, H. M., Pulli, B., Heit, J. J., Telischak, N. A. 2023


    Balloon guide catheters (BGCs) have not been widely adopted, possibly due to the incompatibility of past-generation BGCs with large-bore intermediate catheters. The next-generation BGC is compatible with large-bore catheters. We compared outcomes of thrombectomy cases using BGCs versus conventional guide catheters.We conducted a retrospective study of 110 thrombectomy cases using BGCs (n=55) and non-BGCs (n=55). Sixty consecutive thrombectomy cases in whom the BOBBY BGC was used at a single institution between February 2021 and March 2022 were identified. Of these, 55 BGC cases were 1:1 matched with non-BGC cases by proceduralists, age, gender, stent retriever + aspiration device versus aspiration-only, and site of occlusion. First-pass effect was defined as Thrombolysis In Cerebral Infarction 2b or higher with a single pass.The BGC and non-BGC cohorts had similar mean age (67.2 vs 68.9 years), gender distribution (43.6% vs 47.3% women), median initial National Institutes of Health Stroke Scale score (14 vs 15), and median pretreatment ischemic core volumes (12 mL vs 11.5 mL). BGC and non-BGC cases had similar rates of single pass (60.0% vs 54.6%), first-pass effect (58.2% vs 49.1%), and complications (1.8% vs 9.1%). In aspiration-only cases, the BGC cohort had a significantly higher rate of first-pass effect (100% vs 50.0%, p=0.01). BGC was associated with a higher likelihood of achieving a modified Rankin Scale score of 2 at discharge (OR 7.76, p=0.02). No additional procedural time was required for BGC cases (46.7 vs 48.2 min).BGCs may be safely adopted with comparable procedural efficacy, benefits to aspiration-only techniques, and earlier functional improvement compared with conventional guide catheters.

    View details for DOI 10.1136/jnis-2023-020635

    View details for PubMedID 37793796

  • Non-inferiority of deep learning ischemic stroke segmentation on non-contrast CT within 16-hours compared to expert neuroradiologists. Scientific reports Ostmeier, S., Axelrod, B., Verhaaren, B. F., Christensen, S., Mahammedi, A., Liu, Y., Pulli, B., Li, L., Zaharchuk, G., Heit, J. J. 2023; 13 (1): 16153


    We determined if a convolutional neural network (CNN) deep learning model can accurately segment acute ischemic changes on non-contrast CT compared to neuroradiologists. Non-contrast CT (NCCT) examinations from 232 acute ischemic stroke patients who were enrolled in the DEFUSE 3 trial were included in this study. Three experienced neuroradiologists independently segmented hypodensity that reflected the ischemic core on each scan. The neuroradiologist with the most experience (expert A) served as the ground truth for deep learning model training. Two additional neuroradiologists' (experts B and C) segmentations were used for data testing. The 232 studies were randomly split into training and test sets. The training set was further randomly divided into 5 folds with training and validation sets. A 3-dimensional CNN architecture was trained and optimized to predict the segmentations of expert A from NCCT. The performance of the model was assessed using a set of volume, overlap, and distance metrics using non-inferiority thresholds of 20%, 3 ml, and 3 mm, respectively. The optimized model trained on expert A was compared to test experts B and C. We used a one-sided Wilcoxon signed-rank test to test for the non-inferiority of the model-expert compared to the inter-expert agreement. The final model performance for the ischemic core segmentation task reached a performance of 0.46 ± 0.09 Surface Dice at Tolerance 5mm and 0.47 ± 0.13 Dice when trained on expert A. Compared to the two test neuroradiologists the model-expert agreement was non-inferior to the inter-expert agreement, [Formula: see text]. The before, CNN accurately delineates the hypodense ischemic core on NCCT in acute ischemic stroke patients with an accuracy comparable to neuroradiologists.

    View details for DOI 10.1038/s41598-023-42961-x

    View details for PubMedID 37752162

  • Prediction of delayed cerebral ischemia after cerebral aneurysm rupture using explainable machine learning approach. Interventional neuroradiology : journal of peritherapeutic neuroradiology, surgical procedures and related neurosciences Taghavi, R. M., Zhu, G., Wintermark, M., Kuraitis, G. M., Sussman, E. S., Pulli, B., Biniam, B., Ostmeier, S., Steinberg, G. K., Heit, J. J. 2023: 15910199231170411


    Aneurysmal subarachnoid hemorrhage results in significant mortality and disability, which is worsened by the development of delayed cerebral ischemia. Tests to identify patients with delayed cerebral ischemia prospectively are of high interest.We created a machine learning system based on clinical variables to predict delayed cerebral ischemia in aneurysmal subarachnoid hemorrhage patients. We also determined which variables have the most impact on delayed cerebral ischemia prediction using SHapley Additive exPlanations method.500 aneurysmal subarachnoid hemorrhage patients were identified and 369 met inclusion criteria: 70 patients developed delayed cerebral ischemia (delayed cerebral ischemia+) and 299 did not (delayed cerebral ischemia-). The algorithm was trained based upon age, sex, hypertension (HTN), diabetes, hyperlipidemia, congestive heart failure, coronary artery disease, smoking history, family history of aneurysm, Fisher Grade, Hunt and Hess score, and external ventricular drain placement. Random Forest was selected for this project, and prediction outcome of the algorithm was delayed cerebral ischemia+. SHapley Additive exPlanations was used to visualize each feature's contribution to the model prediction.The Random Forest machine learning algorithm predicted delayed cerebral ischemia: accuracy 80.65% (95% CI: 72.62-88.68), area under the curve 0.780 (95% CI: 0.696-0.864), sensitivity 12.5% (95% CI: -3.7 to 28.7), specificity 94.81% (95% CI: 89.85-99.77), PPV 33.3% (95% CI: -4.39 to 71.05), and NPV 84.1% (95% CI: 76.38-91.82). SHapley Additive exPlanations value demonstrated Age, external ventricular drain placement, Fisher Grade, and Hunt and Hess score, and HTN had the highest predictive values for delayed cerebral ischemia. Lower age, absence of hypertension, higher Hunt and Hess score, higher Fisher Grade, and external ventricular drain placement increased risk of delayed cerebral ischemia.Machine learning models based upon clinical variables predict delayed cerebral ischemia with high specificity and good accuracy.

    View details for DOI 10.1177/15910199231170411

    View details for PubMedID 37070145

  • A case of recurrent aneurysm resulting from dual antiplatelet plus anticoagulation after confirmed aneurysm closure following coil-assisted flow diversion. Radiology case reports Geisbush, T. R., Pulli, B., Wolman, D. N., Pendharkar, A. V., Telischak, N. A. 2022; 17 (11): 4075-4078


    Dual antiplatelet therapy (DAPT) is a management cornerstone for intracranial aneurysms treated with flow diversion. However, combined dual antiplatelet plus anticoagulation (triple therapy) can be indicated in some patients with important associated risks. Here we present the case of a 72-year-old woman with prior history of subarachnoid hemorrhage who was started on triple therapy (enoxaparin and DAPT) following successful flow diversion of an enlarging but unruptured left fetal posterior communicating artery aneurysm. Her post-procedural course was complicated by in-stent thrombosis in the setting of a missed ticagrelor dose and subsequent development of deep venous thrombosis and pulmonary embolism. An early follow-up angiogram confirmed occlusion of the aneurysm. However, after initiation of triple therapy, the aneurysm partially recanalized and her symptoms recurred. Subsequent discontinuation of enoxaparin lead to prompt aneurysm re-occlusion. To our knowledge, this is the first reported instance of confirmed intra-aneurysmal thrombolysis in a successfully treated aneurysm after triple therapy initiation.

    View details for DOI 10.1016/j.radcr.2022.07.091

    View details for PubMedID 36065245

  • Myeloperoxidase exerts anti-tumor activity in glioma after radiotherapy NEOPLASIA Ali, M., Fulci, G., Grigalavicius, M., Pulli, B., Li, A., Wojtkiewicz, G. R., Wang, C., Hsieh, K., Linnoila, J. J., Theodossiou, T. A., Chen, J. W. 2022; 26: 100779


    Host immune response is a critical component in tumorigenesis and immune escape. Radiation is widely used for glioblastoma (GBM) and can induce marked tissue inflammation and substantially alter host immune response. However, the role of myeloperoxidase (MPO), a key enzyme in inflammation and host immune response, in tumorigenesis after radiotherapy is unclear. In this study, we aimed to determine how post-radiation MPO activity influences GBM and outcome.We injected C57BL/6J or MPO-knockout mice with 005 mouse GBM stem cells intracranially. To observe MPO's effects on post-radiation tumor progression, we then irradiated the head with 10 Gy unfractionated and treated the mice with a specific MPO inhibitor, 4-aminobenzoic acid hydrazide (ABAH), or vehicle as control. We performed semi-quantitative longitudinal molecular MRI, enzymatic assays and flow cytometry to assess changes in inflammatory response and tumor size, and tracked survival. We also performed cell culture experiments in murine and human GBM cells to determine the effect of MPO on these cells.Brain irradiation increased the number of monocytes/macrophages and neutrophils, and boosted MPO activity by ten-fold in the glioma microenvironment. However, MPO inhibition dampened radiation-induced inflammation, demonstrating decreased MPO-specific signal on molecular MRI and attenuated neutrophil and inflammatory monocyte/macrophage recruitment to the glioma. Compared to saline-treated mice, both ABAH-treated and MPO-knockout mice had accelerated tumor growth and reduced survival. We further confirmed that MPO decreased tumor cell viability and proliferation in cell cultures.Local radiation to the brain initiated an acute systemic inflammatory response with increased MPO-carrying cells both in the periphery and the GBM, resulting in increased MPO activity in the tumor microenvironment. Inhibition or absence of MPO activity increased tumor growth and decreased host survival, revealing that elevated MPO activity after radiation has an anti-tumor role.

    View details for DOI 10.1016/j.neo.2022.100779

    View details for Web of Science ID 000779992700002

    View details for PubMedID 35247801

    View details for PubMedCentralID PMC8894277

  • Computed Tomography-Based Imaging Algorithms for Patient Selection in Acute Ischemic Stroke. Neuroimaging clinics of North America Pulli, B., Heit, J. J., Wintermark, M. 2021; 31 (2): 235–50


    Computed tomography remains the most widely used imaging modality for evaluating patients with acute ischemic stroke. Landmark trials have used computed tomography imaging to select patients for intravenous thrombolysis and endovascular treatment. This review summarizes the most important acute ischemic stroke trials, provides an outlook of ongoing studies, and proposes possible image algorithms for patient selection. Although evaluation with anatomic computed tomography imaging techniques is sufficient in early window patients, more advanced imaging techniques should be used beyond 6hours from symptoms onset to quantify the ischemic core and evaluate for the salvageable penumbra.

    View details for DOI 10.1016/j.nic.2020.12.002

    View details for PubMedID 33902877

  • Intraoperative Neuromonitoring for Cerebral Arteriovenous Malformation Embolization: A Propensity-Score Matched Retrospective Database Study. Cureus Feng, A. Y., Sussman, E. S., Jin, M. C., Wong, S., Lopez, J., Pulli, B., Heit, J. J., Telischak, N. 2021; 13 (1): e12946


    Introduction The treatment of cerebral arteriovenous malformations (AVMs) may result in neurologic morbidity, particularly when an AVM is located in or adjacent to eloquent brain regions. Intraoperative neurophysiologic monitoring (IONM) may be utilized to reduce the risk of iatrogenic injury during endovascular AVM embolization; however, IONM for endovascular AVM embolization is not ubiquitously the standard of care. Methods Admissions for AVM embolization were assessed from the IBM MarketScan Commercial and Medicare Supplemental databases (IBM Watson Health, Somers, NY). Inclusion criterion for patients was continuous enrollment six months before and after the index encounter. The use of IONM and presence of intracranial hemorrhage (ICH) were noted. Propensity-score matched cohorts with and without IONM were generated to minimize bias between treatment groups (adjusting for age, sex, and comorbidities). Results From 2007 to 2016, there were 16,279 patients diagnosed with cerebral AVM in the MarketScan database. Embolized patients were stratified into IONM and non-IONM cohorts; there were 357 patients in the IONM cohort and 1775 patients in the non-IONM cohort. Provider types were significantly different between cohorts (p<0.005). Unruptured AVMs were significantly more likely to be embolized with adjunctive IONM (17.7%) compared to ruptured AVMs (7.9%) (p<0.005). After balancing for baseline comorbidities, there were 266 patients in the IONM cohort, and 1347 patients in the non-IONM cohort. Among unruptured AVM patients, IONM was linked to a significantly shorter length of stay (2.72 versus 4.92 days; p<0.005), significantly lower rates of complications within 30 days of discharge (0.00% versus 1.88%; p=0.038), and significantly lower total payment ($40,179 versus $50,844; p<0.0001). Conclusion Endovascular embolization for unruptured AVMs performed with adjunctive IONM was associated with shorter length of stay, lower complication rates, and hospitalization costs.

    View details for DOI 10.7759/cureus.12946

    View details for PubMedID 33654622

  • The Promise of Dual-Energy CT in Stroke and Neurovascular Imaging. World neurosurgery Wolman, D. N., Pulli, B. n., Heit, J. J. 2021; 146: 379–80

    View details for DOI 10.1016/j.wneu.2020.12.003

    View details for PubMedID 33607724

  • Multimodal cerebral arteriovenous malformation treatment: a 12-year experience and comparison of key outcomes to ARUBA JOURNAL OF NEUROSURGERY Pulli, B., Chapman, P. H., Ogilvy, C. S., Patel, A. B., Stapleton, C. J., Leslie-Mazwi, T. M., Hirsch, J. A., Carter, B. S., Rabinov, J. D. 2020; 133 (6): 1792-1801


    Curative treatment of unruptured brain arteriovenous malformations (AVMs) remains controversial after the only randomized controlled trial, A Randomized Trial of Unruptured Brain Arteriovenous Malformations (ARUBA), was halted prematurely because interim analysis revealed superiority of the medical management group. In contrast, meta-analyses of retrospective cohorts suggest that intervention is much safer than was found in ARUBA.The authors retrospectively analyzed 318 consecutive adult patients with brain AVMs treated at their institution with embolization, surgery, and/or proton beam radiosurgery. Analysis was performed in 142 ARUBA-eligible patients (baseline modified Rankin Scale [mRS] score 0-1, no history of hemorrhage), and results were compared to primary and secondary outcomes from ARUBA, as well as to natural history cohorts.The annualized stroke rate (hemorrhagic or ischemic) in this cohort was 1.8%, 4.9% in the first 12 months and 0.8% after the first 12 months, which was lower than in natural history studies and the ARUBA medical management arm (p = 0.001). The primary ARUBA endpoint of symptomatic stroke was reached in 13 patients (9.2%), which compares favorably to the ARUBA intervention arm (39.6%, p = 0.0001) and is similar to the ARUBA medical management arm (9.2%, p = 1.0). The secondary ARUBA endpoint (mRS score ≥ 2 at 5 years of follow-up) was reached in 14.3% of patients, compared to 40.5% in the ARUBA intervention arm (p = 0.002) and 16.7% in the ARUBA medical management arm (p = 0.6).This multimodal approach to the selection and treatment of patients with brain AVMs yields good clinical outcomes with key safety endpoints (stroke, death, and mRS score 0-1) better than the ARUBA intervention arm and similar to the ARUBA medical arm at 5 years of follow-up. Results compare favorably to natural history cohorts at longer follow-up times. This suggests that tertiary care centers with integrated programs, expertise in patient selection, and individualized treatment approaches may allow for better clinical outcomes than reported in ARUBA. It supports current registry studies and merits consideration of future randomized controlled trials in patients with brain AVMs.

    View details for DOI 10.3171/2019.8.JNS19998

    View details for Web of Science ID 000616132900002

    View details for PubMedID 31675689

  • Efficacy and safety of embolization of dural arteriovenous fistulas via the ophthalmic artery. Interventional neuroradiology : journal of peritherapeutic neuroradiology, surgical procedures and related neurosciences Mayercik, V. A., Sussman, E. S., Pulli, B., Dodd, R. L., Do, H. M., Telischak, N. A., Marks, M. P., Steinberg, G. K., Chang, S. D., Heit, J. J. 2020: 1591019920969270


    INTRODUCTION: Dural arteriovenous fistulae (DAVF) are vascular lesions with arteriovenous shunting that may be treated with surgical obliteration or endovascular embolization. Some DAVF, such as anterior cranial fossa DAVF (AC-DAVF) derive their arterial supply from ophthalmic artery branches in nearly all cases, and trans-arterial embolization carries a risk of vision loss. We determined the efficacy and safety of trans-ophthalmic artery embolization of DAVF.MATERIALS AND METHODS: We performed a retrospective cohort study of all patients with DAVF treated by trans-ophthalmic artery embolization from 2012 to 2020. Primary outcome was angiographic cure of the DAVF. Secondary outcomes included vision loss, visual impairment, orbital cranial nerve injury, stroke, modified Rankin Scale at 90-days, and mortality.RESULTS: 12 patients met inclusion criteria (9 males; 3 females). 10 patients had AC-DAVF. Patient age was 59.7±9.5 (mean±SD) years. Patients presented with intracranial hemorrhage (4 patients), headache (4 patients), amaurosis fugax (1 patients), or were incidentally discovered (2 patients). DAVF Cognard grades were: II (1 patient), III (6 patients), and IV (5 patients). DAVF were embolized with Onyx (10 patients), nBCA glue (1 patient), and a combination of coils and Onyx (1 patient). DAVF cure was achieved in 11 patients (92%). No patients experienced vision loss, death, or permanent disability. One patient experienced a minor complication of blurry vision attributed to posterior ischemic optic neuropathy. 90-day mRS was 0 (10 patients) and 1 (2 patients).CONCLUSIONS: Trans-ophthalmic artery embolization is an effective and safe treatment for DAVF.

    View details for DOI 10.1177/1591019920969270

    View details for PubMedID 33106085

  • Comparison of predictive grading systems for procedural risk in endovascular treatment of brain arteriovenous malformations: analysis of 104 consecutive patients JOURNAL OF NEUROSURGERY Pulli, B., Stapleton, C. J., Walcott, B. P., Koch, M. J., Raymond, S. B., Leslie-Mazwi, T. M., Rabinov, J. D., Patel, A. B. 2020; 133 (2): 342-350


    Several grading systems for procedural risk in the endovascular treatment of brain arteriovenous malformations (AVMs) have been proposed, including the Buffalo, Puerto Rico, and AVM embocure scoring systems. The authors sought to validate these systems in an independent patient cohort and compare each system to the established Spetzler-Martin (SM) scale.One hundred four consecutive patients underwent adjunctive endovascular embolization of brain AVMs between 2002 and 2016 with the goal of reducing the surgical or hemorrhagic risk before definitive radiosurgical treatment. Baseline clinical and AVM characteristics, complications, and degree of AVM nidus reduction were obtained retrospectively. Univariate and multivariate comparisons and receiver operating characteristic (ROC) curve analyses were performed.Ten major (9.6%) and 16 minor (15.4%) complications were encountered in 24 patients (23.1%). An arterial pedicle size < 1 mm (p = 0.001) and a greater number of pedicles (p = 0.039) were predictors of complication occurrence. Only the Buffalo score predicted the complication rate on univariate (p = 0.039) and multivariate (p = 0.001) analyses. ROC curve analysis revealed a greater area under the curve (AUC) of the Buffalo score (0.703) compared to the Puerto Rico score (p = 0.028), AVM embocure score (AVMES; p = 0.010), and SM grade (SMG; p = 0.030). The Buffalo score, Puerto Rico score, and AVMES but not the SMG predicted > 85% nidus reduction. The AUCs for the different scoring systems were not significantly different.The major complication rate of 9.6% is within the range of rates reported in the literature and emphasizes that brain AVM embolization is not a low-risk procedure. The Buffalo score but not the Puerto Rico score, AVMES, or SMG predicted the endovascular procedural risk. All three endovascular scores but not the SMG predicted a > 85% nidus reduction rate in this cohort embolized as part of a multimodal AVM treatment.

    View details for DOI 10.3171/2019.4.JNS19266

    View details for Web of Science ID 000586087300009

    View details for PubMedID 31200386

  • Dual antiplatelet therapy after carotid artery stenting: trends and outcomes in a large national database. Journal of neurointerventional surgery Sussman, E. S., Jin, M. n., Pendharkar, A. V., Pulli, B. n., Feng, A. n., Heit, J. J., Telischak, N. A. 2020


    While dual antiplatelet therapy (dAPT) is standard of care following carotid artery stenting (CAS), the optimal dAPT regimen and duration has not been established.We canvassed a large national database (IBM MarketScan) to identify patients receiving carotid endarterectomy (CEA) or CAS for treatment of ischemic stroke or carotid artery stenosis from 2007 to 2016. We performed univariable and multivariable regression methods to evaluate the impact of covariates on post-CAS stroke-free survival, including post-discharge antiplatelet therapy.A total of 79 084 patients diagnosed with ischemic stroke or carotid stenosis received CEA (71 178; 90.0%) or CAS (7906; 10.0%). After adjusting for covariates, <180 days prescribed post-CAS P2Y12-inhibition was associated with increased risk for stroke (<90 prescribed days HR=1.421, 95% CI 1.038 to 1.946; 90-179 prescribed days HR=1.484, 95% CI 1.045 to 2.106). The incidence of hemorrhagic complications was higher during the period of prescribed P2Y12-inhibition (1.16% per person-month vs 0.49% per person-month after discontinuation, P<0.001). The rate of extracranial hemorrhage was nearly six-fold higher while on dAPT (6.50% per patient-month vs 1.16% per patient-month, P<0.001), and there was a trend towards higher rate of intracranial hemorrhage that did not reach statistical significance (5.09% per patient-month vs 3.69% per patient-month, P=0.0556). Later hemorrhagic events beyond 30 days post-CAS were significantly more likely to be extracranial (P=0.028).Increased duration of post-CAS dAPT is associated with lower rates of readmissions for stroke, and with increased risk of hemorrhagic complications, particularly extracranial hemorrhage. The potential benefit of prolonging dAPT with regard to ischemic complications must be balanced with the corresponding increased risk of predominantly extracranial hemorrhagic complications.

    View details for DOI 10.1136/neurintsurg-2020-016008

    View details for PubMedID 32414894

  • Initial experience with the Scepter Mini dual-lumen balloon for transophthalmic artery embolization of anterior cranial fossa dural arteriovenous fistulae. Journal of neurointerventional surgery Pulli, B. n., Sussman, E. S., Mayercik, V. n., Steinberg, G. K., Do, H. M., Heit, J. J. 2020


    Precise delivery of liquid embolic agents (LEAs) remains a challenge in the endovascular treatment of dural arteriovenous fistulae (dAVFs) and cerebral arteriovenous malformations (cAVMs). Despite significant advances in the past decade, LEA reflux and catheter navigability remain shortcomings of current endovascular technology, particularly in small and tortuous arteries. The Scepter Mini dual-lumen balloon microcatheter aims to address these issues by decreasing the distal catheter profile (1.6 French) while allowing for a small (2.2 mm diameter) balloon at its tip.We report our initial experience with the Scepter Mini in two patients with anterior cranial fossa dAVFs that were treated with transophthalmic artery embolization.In both patients, the Scepter Mini catheter was able to be safely advanced into the distal ophthalmic artery close to the fistula site, and several centimeters past the origins of the central retinal and posterior ciliary arteries. A single Onyx injection without any reflux resulted in angiographic cure of the dAVF in both cases, and neither patient suffered any vision loss.These initial experiences suggest that the Scepter Mini represents a significant advance in the endovascular treatment of dAVFs and cAVMs and will allow for safer and more efficacious delivery of LEAs into smaller and more distal arteries while diminishing the risk of LEA reflux.

    View details for DOI 10.1136/neurintsurg-2020-016013

    View details for PubMedID 32434799

  • Myeloperoxidase Molecular MRI Reveals Synergistic Combination Therapy in Murine Experimental Autoimmune Neuroinflammation RADIOLOGY Li, A., Wu, Y., Pulli, B., Wojtkiewicz, G. R., Iwamoto, Y., Wang, C., Li, J., Ali, M., Feng, X., Yao, Z., Chen, J. W. 2019; 293 (1): 158-165


    Background Despite advances in immunomodulatory agents, most current therapies for multiple sclerosis target lymphocytes or lymphocytic function. However, therapy response may be less than optimal due to demyelination and axonal damage caused by myeloid cells. Purpose To determine if myeloperoxidase (MPO) molecular MRI can evaluate whether combination therapy targeting both lymphoid and myeloid inflammation can improve autoimmune neuroinflammation compared with either drug alone, even at suboptimal doses. Materials and Methods Four groups of 94 female mice (8-10 weeks old) were induced with experimental autoimmune encephalomyelitis (EAE) from August 2, 2016, to March 30, 2018, and divided into saline control (n = 22), 4-aminobenzoic acid hydrazide (ABAH) therapy group (n = 19), glatiramer acetate (GA) therapy group (n = 22), and combination therapy group (n = 31). Mice were administered suboptimal doses of ABAH, an irreversible inhibitor of MPO; GA, a first-line multiple sclerosis drug; both ABAH and GA; or saline (control). Mice were imaged with bis-5-hydroxytryptamide-diethylenetriaminepentaacetate gadolinium (hereafter, MPO-Gd) MRI. One-way analysis of variance, two-way analysis of variance, Kurskal-Wallis, and log-rank tests were used. P < .05 was considered to indicate statistical significance. Results The combination-treated group showed delayed disease onset (day 11.3 vs day 9.8 for ABAH, day 10.4 for GA, day 9.9 for control; P < .05) and reduced disease severity (clinical score during the acute exacerbation period of 1.8 vs 3.8 for ABAH, 3.1 for GA, 3.9 for control; P < .05). The combination-treated group demonstrated fewer MPO-positive lesions (30.2 vs 73.7 for ABAH, 64.8 for GA, 67.2 for control; P < .05), smaller MPO-positive lesion volume (16.7 mm3 vs 65.2 mm3 for ABAH, 69.9 mm3 for GA, 66.0 mm3 for control; P < .05), and lower intensity of MPO-Gd lesion activation ratio (0.7 vs 1.9 for ABAH, 3.2 for GA, 2.3 for control; P < .05). Reduced disease severity in the combination group was confirmed at histopathologic analysis, where MPO expression (1779 vs 2673 for ABAH, 2898 for GA; P < .05) and demyelination (5.3% vs 9.0% for ABAH, 10.6% for GA; P < .05) were ameliorated. Conclusion Myeloperoxidase molecular MRI can track the treatment response from immunomodulatory drugs even if the drug does not directly target myeloperoxidase, and establishes that combination therapy targeting both myeloid and lymphocytic inflammation is effective for murine autoimmune neuroinflammation, even at suboptimal doses. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Walczak in this issue.

    View details for DOI 10.1148/radiol.2019182492

    View details for Web of Science ID 000486623400024

    View details for PubMedID 31478802

    View details for PubMedCentralID PMC6776885

  • Mouse model of anti-NMDA receptor post-herpes simplex encephalitis NEUROLOGY-NEUROIMMUNOLOGY & NEUROINFLAMMATION Linnoila, J., Pulli, B., Armangue, T., Planaguma, J., Narsimhan, R., Schob, S., Zeller, M. G., Dalmau, J., Chen, J. 2019; 6 (2): e529


    To develop an endogenous rodent model of postinfectious anti-NMDA receptor (NMDAR) encephalitis.Six mice were inoculated intranasally with herpes simplex virus (HSV) 1 and subsequently treated with acyclovir for 2 weeks. Serum was collected at 3, 6, and 8 weeks postinoculation and tested for NMDAR antibodies through a cell-based assay. Eight weeks postinoculation, mice were killed and their brains were sectioned and immunostained with antibodies to postsynaptic density (PSD)-95 and NMDARs. Colocalization of hippocampal PSD-95 and NMDAR clusters, representing postsynaptic membrane NMDARs, was quantified via confocal imaging. Hippocampi were additionally analyzed for NMDAR and PSD-95 protein using Western blot analysis.Four of 6 mice (67%) developed serum antibodies to NMDARs: 1 at 3 weeks, 1 at 6 weeks, and 2 at 8 weeks postinoculation. As compared to inoculated mice that did not develop NMDAR antibodies, immunofluorescence staining revealed decreased hippocampal postsynaptic membrane NMDARs in mice with serum antibodies at 8 weeks postinoculation. Western blot analysis showed that mice that had NMDAR antibodies at 8 weeks had decreased total NMDAR but not PSD-95 protein in hippocampal extracts (p < 0.05).Mice inoculated intranasally with HSV-1 developed serum NMDAR antibodies. These antibodies were associated with reduced hippocampal NMDARs, as has been shown in previous models where antibodies from patients with anti-NMDAR encephalitis were infused into mice, paving the way for future studies into the pathophysiology of autoimmune encephalitides.

    View details for DOI 10.1212/NXI.0000000000000529

    View details for Web of Science ID 000473112600006

    View details for PubMedID 30697582

    View details for PubMedCentralID PMC6340334

  • Multimodal Molecular Imaging Demonstrates Myeloperoxidase Regulation of Matrix Metalloproteinase Activity in Neuroinflammation MOLECULAR NEUROBIOLOGY Zhang, Y., Dong, H., Seeburg, D. P., Wojtkiewicz, G. R., Waterman, P., Pulli, B., Forghani, R., Ali, M., Iwamoto, Y., Swirski, F. K., Chen, J. W. 2019; 56 (2): 954-962


    Myeloperoxidase (MPO) has paradoxically been found to be able to both activate matrix metalloproteinases (MMPs) as well as inhibit MMPs. However, these regulatory effects have not yet been observed in vivo, and it is unclear which pathway is relevant in vivo. We aim to track MPO regulation of MMP activity in living animals in neuroinflammation. Mice induced with experimental autoimmune encephalomyelitis (EAE), a mouse model of neuroinflammation and multiple sclerosis, were treated with either the MPO-specific inhibitor 4-aminobenzoic acid hydrazide or saline as control. Mice underwent concurrent magnetic resonance imaging (MRI) with the MPO-specific molecular imaging agent MPO-Gd and fluorescence molecular tomography (FMT) with the MMP-targeting agent MMPsense on day 12 after induction. Biochemical and histopathological correlations were performed. Utilizing concurrent MRI and FMT imaging, we found reduced MMP activity in the brain with MPO inhibition, demonstrating MPO activity positively regulates MMP activity in vivo. In vivo MMPSense activation and MMP-9 activity correlated with MPO-Gd+ lesion volume and disease severity. This was corroborated by in vitro assays and histopathological analyses that showed MMP activity and MMP-9+ cells correlated with MPO activity and MPO+ cells. In conclusion, multimodal molecular imaging demonstrates for the first time MPO regulation of MMP activity in living animals. This approach could serve as a model to study the interactions of other biologically interesting molecules in living organisms.

    View details for DOI 10.1007/s12035-018-1137-2

    View details for Web of Science ID 000460470300013

    View details for PubMedID 29808380

    View details for PubMedCentralID PMC6261713

  • A versatile imaging platform with fluorescence and CT imaging capabilities that detects myeloperoxidase activity and inflammation at different scales THERANOSTICS Wang, C., Pulli, B., Motlagh, N., Li, A., Wojtkiewicz, G. R., Schmidt, S. P., Wu, Y., Zeller, M. G., Chen, J. W. 2019; 9 (25): 7525-7536


    Aberrant innate immune response drives the pathophysiology of many diseases. Myeloperoxidase (MPO) is a highly oxidative enzyme secreted by activated myeloid pro-inflammatory immune cells such as neutrophils and macrophages, and is a key mediator of the damaging innate immune response. Current technologies for detecting MPO activity in living organisms are sparse and suffer from any combination of low specificity, low tissue penetration, or low spatial resolution. We describe a versatile imaging platform to detect MPO activity using an activatable construct conjugated to a biotin moiety (MPO-activatable biotinylated sensor, MABS) that allows monitoring the innate immune response and its modulation at different scales and settings. Methods: We designed and synthesized MABS that contains MPO-specific and biotin moieties, and validated its specificity and sensitivity combining with streptavidin-labeled fluorescent agent and gold nanoparticles imaging in vitro and in vivo in multiple mouse models of inflammation and infection, including Matrigel implant, dermatitis, cellulitis, cerebritis and complete Fraud's adjuvant (CFA)-induced inflammation. Results: MABS MPO imaging non-invasively detected varying MPO concentrations, MPO inhibition, and MPO deficiency in vivo with high sensitivity and specificity. MABS can be used to obtain not only a fluorescence imaging agent, but also a CT imaging agent, conferring molecular activity information to a structural imaging modality. Importantly, using this method on tissue-sections, we found that MPO enzymatic activity does not always co-localize with MPO protein detected with conventional techniques (e.g., immunohistochemistry), underscoring the importance of monitoring enzymatic activity. Conclusion: By choosing from different available secondary probes, MABS can be used to create systems suitable to investigate and image MPO activity at different scales and settings.

    View details for DOI 10.7150/thno.36264

    View details for Web of Science ID 000489762700004

    View details for PubMedID 31695784

    View details for PubMedCentralID PMC6831463

  • Combined adult neurogenesis and BDNF mimic exercise effects on cognition in an Alzheimer's mouse model SCIENCE Choi, S., Bylykbashi, E., Chatila, Z. K., Lee, S. W., Pulli, B., Clemenson, G. D., Kim, E., Rompala, A., Oram, M. K., Asselin, C., Aronson, J., Zhang, C., Miller, S. J., Lesinski, A., Chen, J. W., Kim, D., van Praag, H., Spiegelman, B. M., Gage, F. H., Tanzi, R. E. 2018; 361 (6406): 991-+


    Adult hippocampal neurogenesis (AHN) is impaired before the onset of Alzheimer's disease (AD) pathology. We found that exercise provided cognitive benefit to 5×FAD mice, a mouse model of AD, by inducing AHN and elevating levels of brain-derived neurotrophic factor (BDNF). Neither stimulation of AHN alone, nor exercise, in the absence of increased AHN, ameliorated cognition. We successfully mimicked the beneficial effects of exercise on AD mice by genetically and pharmacologically inducing AHN in combination with elevating BDNF levels. Suppressing AHN later led to worsened cognitive performance and loss of preexisting dentate neurons. Thus, pharmacological mimetics of exercise, enhancing AHN and elevating BDNF levels, may improve cognition in AD. Furthermore, applied at early stages of AD, these mimetics may protect against subsequent neuronal cell death.

    View details for DOI 10.1126/science.aan8821

    View details for Web of Science ID 000443892700038

    View details for PubMedID 30190379

  • Molecular MR Imaging of Myeloperoxidase Distinguishes Steatosis from Steatohepatitis in Nonalcoholic Fatty Liver Disease RADIOLOGY Pulli, B., Wojtkiewicz, G., Iwamoto, Y., Ali, M., Zeller, M. W., Bure, L., Wang, C., Choi, Y., Masia, R., Guimaraes, A. R., Corey, K. E., Chen, J. W. 2017; 284 (2): 390-400


    Purpose To test whether MPO-Gd, an activatable molecular magnetic resonance (MR) imaging agent specific for myeloperoxidase (MPO) activity, could detect MPO activity in nonalcoholic steatohepatitis (NASH) mouse models and human liver biopsy samples. Materials and Methods In this study, 20 leptin receptor-deficient and three MPO knockout mice were injected with endotoxin (lipopolysaccharide) or fed a methionine and choline-deficient (MCD) diet to induce experimental NASH and underwent MR imaging with MPO-Gd. Saline-injected and control diet-fed leptin receptor-deficient mice were used as respective controls. MPO protein and activity measurements and histologic analyses were performed. Eleven human liver biopsy samples underwent MPO-Gd-enhanced MR imaging ex vivo and subsequent histologic evaluation. Results were compared with Student t test or Mann-Whitney U test. Results With endotoxin, a significantly increased contrast-to-noise ratio (CNR) was found compared with sham (mean CNR, 1.81 [95% confidence interval {CI}: 1.53, 2.10] vs 1.02 [95% CI: 0.89, 1.14]; P = .03) at MPO-Gd MR imaging. In the diet-induced NASH model, an increased CNR was also found compared with sham mice (mean CNR, 1.33 [95% CI: 1.27, 1.40] vs 0.98 [95% CI: 0.83, 1.12]; P = .008). Conversely, CNR remained at baseline in NASH mice imaged with gadopentetate dimeglumine and in MPO knockout NASH mice with MPO-Gd, which proves specificity of MPO-Gd. Ex vivo molecular MR imaging of liver biopsy samples from NASH and control patients confirmed results from animal studies (mean CNR for NASH vs control patients, 2.61 [95% CI: 1.48, 3.74] vs 1.29 [95% CI: 1.06, 1.52]; P = .004). Conclusion MPO-Gd showed elevated MPO activity in NAFLD mouse models and human liver biopsy samples. © RSNA, 2017 Online supplemental material is available for this article. An earlier incorrect version of this article appeared online. This article was corrected on April 6, 2017.

    View details for DOI 10.1148/radiol.2017160588

    View details for Web of Science ID 000405797200010

    View details for PubMedID 28358240

    View details for PubMedCentralID PMC5548451

  • Kawasaki disease with giant coronary artery aneurysms CORONARY ARTERY DISEASE Hedgire, S., Pulli, B., Lahoud-Rahme, M., Beroukhim, R. S., Rosales, A. M., Ghoshhajra, B. 2017; 28 (2): 177-179

    View details for DOI 10.1097/MCA.0000000000000437

    View details for Web of Science ID 000393961200015

    View details for PubMedID 27755008

  • Spinal Cord Inflammation: Molecular Imaging after Thoracic Aortic Ischemia Reperfusion Injury RADIOLOGY Albadawi, H., Chen, J. W., Oklu, R., Wu, Y., Wojtkiewicz, G., Pulli, B., Milner, J. D., Cambria, R. P., Watkins, M. T. 2017; 282 (1): 202-211


    Purpose To evaluate whether noninvasive molecular imaging technologies targeting myeloperoxidase (MPO) can reveal early inflammation associated with spinal cord injury after thoracic aortic ischemia-reperfusion (TAR) in mice. Materials and Methods The study was approved by the institutional animal care and use committee. C57BL6 mice that were 8-10 weeks old underwent TAR (n = 55) or sham (n = 26) surgery. Magnetic resonance (MR) imaging (n = 6) or single photon emission computed tomography (SPECT)/computed tomography (CT) (n = 15) studies targeting MPO activity were performed after intravenous injection of MPO sensors (bis-5-hydroxytryptamide-tetraazacyclododecane [HT]-diethyneletriaminepentaacetic acid [DTPA]-gadolinium or indium 111-bis-5-HT-DTPA, respectively). Immunohistochemistry and flow cytometry were used to identify myeloid cells and neuronal loss. Proinflammatory cytokines, keratinocyte chemoattractant (KC), and interleukin 6 (IL-6) were measured with enzyme-linked immunosorbent assay. Statistical analyses were performed by using nonparametric tests and the Pearson correlation coefficient. P < .05 was considered to indicate a significant difference. Results Myeloid cells infiltrated into the injured cord at 6 and 24 hours after TAR. MR imaging confirmed the presence of ischemic lesions associated with mild MPO-mediated enhancement in the thoracolumbar spine at 24 hours compared with the sham procedure. SPECT/CT imaging of MPO activity showed marked MPO-sensor retention at 6 hours (P = .003) that continued to increase at 24 hours after TAR (P = .0001). The number of motor neurons decreased substantially at 24 hours after TAR (P < .01), which correlated inversely with in vivo inflammatory changes detected at molecular imaging (r = 0.64, P = .0099). MPO was primarily secreted by neutrophils, followed by lymphocyte antigen 6 complexhigh monocytes and/or macrophages. There were corresponding increased levels of proinflammatory cytokines KC (P = .0001) and IL-6 (P = .0001) that mirrored changes in MPO activity. Conclusion MPO is a suitable imaging biomarker for identifying and tracking inflammatory damage in the spinal cord after TAR in a mouse model. © RSNA, 2016 Online supplemental material is available for this article.

    View details for DOI 10.1148/radiol.2016152222

    View details for Web of Science ID 000395519800022

    View details for PubMedID 27509542

    View details for PubMedCentralID PMC5207124

  • Myeloperoxidase Inhibition Improves Ventricular Function and Remodeling AfterExperimental Myocardial Infarction. JACC. Basic to translational science Ali, M., Pulli, B., Courties, G., Tricot, B., Sebas, M., Iwamoto, Y., Hilgendorf, I., Schob, S., Dong, A., Zheng, W., Skoura, A., Kalgukar, A., Cortes, C., Ruggeri, R., Swirski, F. K., Nahrendorf, M., Buckbinder, L., Chen, J. W. 2016; 1 (7): 633-643


    PF-1355 is an oral myeloperoxidase (MPO) inhibitor that successfully decreased elevated MPO activity in mouse myocardial infarction models. Short duration PF-1355 treatment for 7 days decreased the number of inflammatory cells and attenuated left ventricular dilation. Cardiac function and remodeling improved when treatment was increased to 21 days. Better therapeutic effect was further achieved with early compared with delayed treatment initiation (1 h vs. 24 h after infarction). In conclusion, PF-1355 treatment protected a mouse heart from acute and chronic effects of MI, and this study paves the way for future translational studies investigating this class of drugs in cardiovascular diseases.

    View details for DOI 10.1016/j.jacbts.2016.09.004

    View details for PubMedID 30167547

  • Surface biotinylation of cytotoxic T lymphocytes for in vivo tracking of tumor immunotherapy in murine models CANCER IMMUNOLOGY IMMUNOTHERAPY Li, A., Wu, Y., Linnoila, J., Pulli, B., Wang, C., Zeller, M., Ali, M., Lewandrowski, G. K., Li, J., Tricot, B., Keliher, E., Wojtkiewicz, G. R., Fulci, G., Feng, X., Tannous, B. A., Yao, Z., Chen, J. W. 2016; 65 (12): 1545-1554


    Currently, there is no stable and flexible method to label and track cytotoxic T lymphocytes (CTLs) in vivo in CTL immunotherapy. We aimed to evaluate whether the sulfo-hydroxysuccinimide (NHS)-biotin-streptavidin (SA) platform could chemically modify the cell surface of CTLs for in vivo tracking. CD8+ T lymphocytes were labeled with sulfo-NHS-biotin under different conditions and then incubated with SA-Alexa647. Labeling efficiency was proportional to sulfo-NHS-biotin concentration. CD8+ T lymphocytes could be labeled with higher efficiency with sulfo-NHS-biotin in DPBS than in RPMI (P < 0.05). Incubation temperature was not a key factor. CTLs maintained sufficient labeling for at least 72 h (P < 0.05), without altering cell viability. After co-culturing labeled CTLs with mouse glioma stem cells (GSCs) engineered to present biotin on their surface, targeting CTLs could specifically target biotin-presenting GSCs and inhibited cell proliferation (P < 0.01) and tumor spheres formation. In a biotin-presenting GSC brain tumor model, targeting CTLs could be detected in biotin-presenting gliomas in mouse brains but not in the non-tumor-bearing contralateral hemispheres (P < 0.05). In vivo fluorescent molecular tomography imaging in a subcutaneous U87 mouse model confirmed that targeting CTLs homed in on the biotin-presenting U87 tumors but not the control U87 tumors. PET imaging with 89Zr-deferoxamine-biotin and SA showed a rapid clearance of the PET signal over 24 h in the control tumor, while only minimally decreased in the targeted tumor. Thus, sulfo-NHS-biotin-SA labeling is an efficient method to noninvasively track the migration of adoptive transferred CTLs and does not alter CTL viability or interfere with CTL-mediated cytotoxic activity.

    View details for DOI 10.1007/s00262-016-1911-9

    View details for Web of Science ID 000387595000010

    View details for PubMedID 27722909

    View details for PubMedCentralID PMC5101144

  • Microstructural Changes in Absence Seizure Children: A Diffusion Tensor Magnetic Resonance Imaging Study PEDIATRICS AND NEONATOLOGY Liang, J., Lee, S., Pulli, B., Chen, J. W., Kao, S., Tsang, Y., Hsieh, K. 2016; 57 (4): 318-325


    Absence seizures are a subtype of epileptic seizures clinically characterized by transient alterations in states of consciousness and by electroencephalography indicating diffuse spike-wave discharges (SWD). Conventional brain magnetic resonance imaging (MRI) is not routinely used to establish the diagnosis, but rather to rule out other diseases. The present study investigated tissue integrity in children with SWD epilepsy using diffusion tensor imaging (DTI).Magnetic resonance imaging (MRI)-DTI was conducted in 18 patients with absence seizures and 10 control participants. Brain areas were evaluated using diffusion maps, and fractional anisotropy (FA), mean diffusivity (MD), parallel diffusivity (λ||), and perpendicular diffusivity (λ⊥) values were extracted and analyzed. Tractography at the regions of abnormal diffusion indices was then reconstructed in each group, and tract symmetry was evaluated by an index of asymmetry (AI). Statistical analyses were performed using nonparametric Mann-Whitney U tests, with p values < 0.05 indicating statistical significance.Compared to the control group, patients with SWD epilepsy had lower FA values and higher MD values at the genu of the corpus callosum. There was also a stronger negative correlation between MD and FA values at the genu of the corpus callosum in patients than in control participants. The AI for the fiber tracts through the genu of the corpus callosum in the SWD group was significantly higher than that of the control group, indicating that tract distribution was more asymmetric in patients with epilepsy. There were no significant differences between groups in diffusion indices for other brain areas.We observed microstructural changes in the genu of the corpus callosum, as well as reduced FA values, increased λ⊥ values, increased MD values, and asymmetric distribution of fiber tracts, indicating that DTI is more sensitive than conventional MRI to detect brain abnormalities in children with absence seizures.

    View details for DOI 10.1016/j.pedneo.2015.10.003

    View details for Web of Science ID 000386990500010

    View details for PubMedID 26750405

  • Myeloperoxidase Nuclear Imaging for Epileptogenesis RADIOLOGY Zhang, Y., Seeburg, D. P., Pulli, B., Wojtkiewicz, G. R., Bure, L., Atkinson, W., Schob, S., Iwamoto, Y., Ali, M., Zhang, W., Rodriguez, E., Milewski, A., Keliher, E. J., Wang, C., Pan, Y., Swirski, F. K., Chen, J. W. 2016; 278 (3): 822-830


    To determine if myeloperoxidase (MPO) is involved in epileptogenesis and if molecular nuclear imaging can be used to noninvasively map inflammatory changes in epileptogenesis.The animal and human studies were approved by the institutional review boards. Pilocarpine-induced epileptic mice were treated with 4-aminobenzoic acid hydrazide (n = 46), a specific irreversible MPO inhibitor, or saline (n = 42). Indium-111-bis-5-hydroxytryptamide-diethylenetriaminepentaacetate was used to image brain MPO activity (n = 6 in the 4-aminobenzoic acid hydrazide and saline groups; n = 5 in the sham group) by using single photon emission computed tomography/computed tomography. The role of MPO in the development of spontaneous recurrent seizures was assessed by means of clinical symptoms and biochemical and histopathologic data. Human brain specimens from a patient with epilepsy and a patient without epilepsy were stained for MPO. The Student t test, one-way analysis of variance, and Mann-Whitney and Kruskal-Wallis tests were used. Differences were regarded as significant if P was less than .05.MPO and leukocytes increased in the brain during epileptogenesis (P < .05). Blocking MPO delayed spontaneous recurrent seizures (99.6 vs 142 hours, P = .016), ameliorated the severity of spontaneous recurrent seizures (P < .05), and inhibited mossy fiber sprouting (Timm index, 0.31 vs 0.03; P = .003). Matrix metalloproteinase activity was upregulated during epileptogenesis in an MPO-dependent manner (1.44 vs 0.94 U/mg, P = .049), suggesting that MPO acts upstream of matrix metalloproteinases. MPO activity was mapped during epileptogenesis in vivo in the hippocampal regions. Resected temporal lobe tissue from a human patient with refractory epilepsy but not the temporal lobe tissue from a patient without seizures demonstrated positive MPO immunostaining, suggesting high translational potential for this imaging technology.The findings of this study highlight an important role for MPO in epileptogenesis and show MPO to be a potential therapeutic target and imaging biomarker for epilepsy.

    View details for DOI 10.1148/radiol.2015141922

    View details for Web of Science ID 000377703400020

    View details for PubMedID 26397127

    View details for PubMedCentralID PMC4770943

  • Myeloperoxidase-Hepatocyte-Stellate Cell Cross Talk Promotes Hepatocyte Injury and Fibrosis in Experimental Nonalcoholic Steatohepatitis ANTIOXIDANTS & REDOX SIGNALING Pulli, B., Ali, M., Iwamoto, Y., Zeller, M. G., Schob, S., Linnoila, J. J., Chen, J. W. 2015; 23 (16): 1255-1269


    Myeloperoxidase (MPO), a highly oxidative enzyme secreted by leukocytes has been implicated in human and experimental nonalcoholic steatohepatitis (NASH), but the underlying mechanisms remain unknown. In this study, we investigated how MPO contributes to progression from steatosis to NASH.In C57Bl/6J mice fed a diet deficient in methionine and choline to induce NASH, neutrophils and to a lesser extent inflammatory monocytes are markedly increased compared with sham mice and secrete abundant amounts of MPO. Through generation of HOCl, MPO directly causes hepatocyte death in vivo. In vitro experiments demonstrate mitochondrial permeability transition pore induction via activation of SAPK/JNK and PARP. MPO also contributes to activation of hepatic stellate cells (HSCs), the most important source of collagen in the liver. In vitro MPO-activated HSCs have an activation signature (MAPK and PI3K-AKT phosphorylation) and upregulate COL1A1, α-SMA, and CXCL1. MPO-derived oxidative stress also activates transforming growth factor β (TGF-β) in vitro, and TGF-β signaling inhibition with SB-431542 decreased steatosis and fibrosis in vivo. Conversely, congenital absence of MPO results in reduced hepatocyte injury, decreased levels of TGF-β, fewer activated HSCs, and less severe fibrosis in vivo.Cumulatively, these findings demonstrate important cross talk between inflammatory myeloid cells, hepatocytes, and HSCs via MPO and establish MPO as part of a proapoptotic and profibrotic pathway of progression in NASH, as well as a potential therapeutic target to ameliorate this disease.

    View details for DOI 10.1089/ars.2014.6108

    View details for Web of Science ID 000366330900001

    View details for PubMedID 26058518

    View details for PubMedCentralID PMC4677570

  • Gelsolin decreases actin toxicity and inflammation in murine multiple sclerosis JOURNAL OF NEUROIMMUNOLOGY Li-ChunHsieh, K., Schob, S., Zeller, M. G., Pulli, B., Ali, M., Wang, C., Chiou, T., Tsang, Y., Lee, P., Stossel, T. P., Chen, J. W. 2015; 287: 36-42


    Gelsolin is the fourth most abundant protein in the body and its depletion in the blood has been found in multiple sclerosis (MS) patients. How gelsolin affects the MS brain has not been studied. We found that while the secreted form of gelsolin (pGSN) decreased in the blood of experimental autoimmune encephalomyelitis (EAE) mice, pGSN concentration increased in the EAE brain. Recombinant human pGSN (rhp-GSN) decreased extracellular actin and myeloperoxidase activity in the brain, resulting in reduced disease activity and less severe clinical disease, suggesting that gelsolin could be a potential therapeutic target for MS.

    View details for DOI 10.1016/j.jneuroim.2015.08.006

    View details for Web of Science ID 000363347300008

    View details for PubMedID 26439960

    View details for PubMedCentralID PMC4595933

  • Multiple Sclerosis: Myeloperoxidase Immunoradiology Improves Detection of Acute and Chronic Disease in Experimental Model RADIOLOGY Pulli, B., Bure, L., Wojtkiewicz, G. R., Iwamoto, Y., Ali, M., Li, D., Schob, S., Hsieh, K., Jacobs, A. H., Chen, J. W. 2015; 275 (2): 480-489


    To test if MPO-Gd, a gadolinium-based magnetic resonance (MR) imaging probe that is sensitive and specific for the proinflammatory and oxidative enzyme myeloperoxidase (MPO), which is secreted by certain inflammatory cells, is more sensitive than diethylenetriaminepentaacetic acid (DTPA)-Gd in revealing early subclinical and chronic disease activity in the brain in experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis.The protocol for animal experiments was approved by the institutional animal care committee. A total of 61 female SJL mice were induced with EAE. Mice underwent MPO-Gd- or DTPA-Gd-enhanced MR imaging on days 6, 8, and 10 after induction, before clinical disease develops, and during chronic disease at remission and the first relapse. Brains were harvested at these time points for flow cytometric evaluation of immune cell subtypes and immunohistochemistry. Statistical analysis was performed, and P < .05 was considered to indicate a significant difference.MPO-Gd helps detect earlier (5.2 vs 2.3 days before symptom onset, P = .004) and more (3.1 vs 0.3, P = .008) subclinical inflammatory lesions compared with DTPA-Gd, including in cases in which there was no evidence of overt blood-brain barrier (BBB) breakdown detected with DTPA-Gd enhancement. The number of MPO-Gd-enhancing lesions correlated with early infiltration of MPO-secreting monocytes and neutrophils into the brain (r = 0.91). MPO-Gd also helped detect more lesions during subclinical disease at remission (5.5 vs 1.3, P = .006) and at the first relapse (9.0 vs 2.7, P = .03) than DTPA-Gd, which also correlated well with the presence and accumulation of MPO-secreting inflammatory cells in the brain (r = 0.93).MPO-Gd specifically reveals lesions with inflammatory monocytes and neutrophils, which actively secrete MPO. These results demonstrate the feasibility of detection of subclinical inflammatory disease activity in vivo, which is different from overt BBB breakdown.

    View details for DOI 10.1148/radiol.14141495

    View details for Web of Science ID 000355987700020

    View details for PubMedID 25494298

    View details for PubMedCentralID PMC4455671

  • Molecular Imaging of Macrophage Enzyme Activity in Cardiac Inflammation CURRENT CARDIOVASCULAR IMAGING REPORTS Ali, M., Pulli, B., Chen, J. W. 2014; 7 (4): 9258


    Molecular imaging is highly advantageous as various insidious inflammatory events can be imaged in a serial and quantitative fashion. Combined with the conventional imaging modalities like computed tomography (CT), magnetic resonance (MR) and nuclear imaging, it helps us resolve the extent of ongoing pathology, quantify inflammation and predict outcome. Macrophages are increasingly gaining importance as an imaging biomarker in inflammatory cardiovascular diseases. Macrophages, recruited to the site of injury, internalize necrotic or foreign material. Along with phagocytosis, activated macrophages release proteolytic enzymes like matrix metalloproteinases (MMPs) and cathepsins into the extracellular environment. Pro-inflammatory monocytes and macrophages also induce tissue oxidative damage through the inflammatory enzyme myeloperoxidase (MPO). In this review we will highlight recent advances in molecular macrophage imaging. Particular stress will be given to macrophage functional and enzymatic activity imaging which targets phagocytosis, proteolysis and myeloperoxidase activity imaging.

    View details for DOI 10.1007/s12410-014-9258-0

    View details for Web of Science ID 000219815400002

    View details for PubMedID 24729833

    View details for PubMedCentralID PMC3979571

  • Imaging Neuroinflammation - from Bench to Bedside. Journal of clinical & cellular immunology Pulli, B., Chen, J. W. 2014; 5


    Neuroinflammation plays a central role in a variety of neurological diseases, including stroke, multiple sclerosis, Alzheimer's disease, and malignant CNS neoplasms, among many other. Different cell types and molecular mediators participate in a cascade of events in the brain that is ultimately aimed at control, regeneration and repair, but leads to damage of brain tissue under pathological conditions. Non-invasive molecular imaging of key players in the inflammation cascade holds promise for identification and quantification of the disease process before it is too late for effective therapeutic intervention. In this review, we focus on molecular imaging techniques that target inflammatory cells and molecules that are of interest in neuroinflammation, especially those with high translational potential. Over the past decade, a plethora of molecular imaging agents have been developed and tested in animal models of (neuro)inflammation, and a few have been translated from bench to bedside. The most promising imaging techniques to visualize neuroinflammation include MRI, positron emission tomography (PET), single photon emission computed tomography (SPECT), and optical imaging methods. These techniques enable us to image adhesion molecules to visualize endothelial cell activation, assess leukocyte functions such as oxidative stress, granule release, and phagocytosis, and label a variety of inflammatory cells for cell tracking experiments. In addition, several cell types and their activation can be specifically targeted in vivo, and consequences of neuroinflammation such as neuronal death and demyelination can be quantified. As we continue to make progress in utilizing molecular imaging technology to study and understand neuroinflammation, increasing efforts and investment should be made to bring more of these novel imaging agents from the "bench to bedside."

    View details for PubMedID 25525560

  • Measuring Myeloperoxidase Activity in Biological Samples PLOS ONE Pulli, B., Ali, M., Forghani, R., Schob, S., Hsieh, K. C., Wojtkiewicz, G., Linnoila, J. J., Chen, J. W. 2013; 8 (7): e67976


    Enzymatic activity measurements of the highly oxidative enzyme myeloperoxidase (MPO), which is implicated in many diseases, are widely used in the literature, but often suffer from nonspecificity and lack of uniformity. Thus, validation and standardization are needed to establish a robust method that is highly specific, sensitive, and reproducible for assaying MPO activity in biological samples.We found conflicting results between in vivo molecular MR imaging of MPO, which measures extracellular activity, and commonly used in vitro MPO activity assays. Thus, we established and validated a protocol to obtain extra- and intracellular MPO from murine organs. To validate the MPO activity assays, three different classes of MPO activity assays were used in spike and recovery experiments. However, these assay methods yielded inconsistent results, likely because of interfering substances and other peroxidases present in tissue extracts. To circumvent this, we first captured MPO with an antibody. The MPO activity of the resultant samples was assessed by ADHP and validated against samples from MPO-knockout mice in murine disease models of multiple sclerosis, steatohepatitis, and myocardial infarction. We found the measurements performed using this protocol to be highly specific and reproducible, and when performed using ADHP, to be highly sensitive over a broad range. In addition, we found that intracellular MPO activity correlated well with tissue neutrophil content, and can be used as a marker to assess neutrophil infiltration in the tissue.We validated a highly specific and sensitive assay protocol that should be used as the standard method for all MPO activity assays in biological samples. We also established a method to obtain extra- and intracellular MPO from murine organs. Extracellular MPO activity gives an estimate of the oxidative stress in inflammatory diseases, while intracellular MPO activity correlates well with tissue neutrophil content. A detailed step-by-step protocol is provided.

    View details for DOI 10.1371/journal.pone.0067976

    View details for Web of Science ID 000321425300033

    View details for PubMedID 23861842

    View details for PubMedCentralID PMC3702519

  • Demyelinating Diseases: Myeloperoxidase as an Imaging Biomarker and Therapeutic Target RADIOLOGY Forghani, R., Wojtkiewicz, G. R., Zhang, Y., Seeburg, D., Bautz, B. M., Pulli, B., Milewski, A. R., Atkinson, W. L., Iwamoto, Y., Zhang, E. R., Etzrodt, M., Rodriguez, E., Robbins, C. S., Swirski, F. K., Weissleder, R., Chen, J. W. 2012; 263 (2): 451-460


    To evaluate myeloperoxidase (MPO) as a newer therapeutic target and bis-5-hydroxytryptamide-diethylenetriaminepentaacetate-gadolinium (Gd) (MPO-Gd) as an imaging biomarker for demyelinating diseases such as multiple sclerosis (MS) by using experimental autoimmune encephalomyelitis (EAE), a murine model of MS.Animal experiments were approved by the institutional animal care committee. EAE was induced in SJL mice by using proteolipid protein (PLP), and mice were treated with either 4-aminobenzoic acid hydrazide (ABAH), 40 mg/kg injected intraperitoneally, an irreversible inhibitor of MPO, or saline as control, and followed up to day 40 after induction. In another group of SJL mice, induction was performed without PLP as shams. The mice were imaged by using MPO-Gd to track changes in MPO activity noninvasively. Imaging results were corroborated by enzymatic assays, flow cytometry, and histopathologic analyses. Significance was computed by using the t test or Mann-Whitney U test.There was a 2.5-fold increase in myeloid cell infiltration in the brain (P = .026), with a concomitant increase in brain MPO level (P = .0087). Inhibiting MPO activity with ABAH resulted in decrease in MPO-Gd-positive lesion volume (P = .012), number (P = .009), and enhancement intensity (P = .03) at MR imaging, reflecting lower local MPO activity (P = .03), compared with controls. MPO inhibition was accompanied by decreased demyelination (P = .01) and lower inflammatory cell recruitment in the brain (P < .0001), suggesting a central MPO role in inflammatory demyelination. Clinically, MPO inhibition significantly reduced the severity of clinical symptoms (P = .0001) and improved survival (P = .0051) in mice with EAE.MPO may be a key mediator of myeloid inflammation and tissue damage in EAE. Therefore, MPO could represent a promising therapeutic target, as well as an imaging biomarker, for demyelinating diseases and potentially for other diseases in which MPO is implicated.

    View details for DOI 10.1148/radiol.12111593

    View details for Web of Science ID 000303104300016

    View details for PubMedID 22438365

    View details for PubMedCentralID PMC3329272

  • Repeat Rates in Digital Chest Radiography and Strategies for Improvement JOURNAL OF THORACIC IMAGING Fintelmann, F., Pulli, B., Abedi-Tari, F., Trombley, M., Shore, M., Shepard, J., Rosenthal, D. I. 2012; 27 (3): 148-151


    To determine the repeat rate (RR) of chest radiographs acquired with portable computed radiography (CR) and installed direct radiography (DR) and to develop and assess strategies designed to decrease the RR.The RR and reasons for repeated digital chest radiographs were documented over the course of 16 months while a task force of thoracic radiologists, technologist supervisors, technologists, and information technology specialists continued to examine the workflow for underlying causes. Interventions decreasing the RR were designed and implemented.The initial RR of digital chest radiographs was 3.6% (138/3818) for portable CR and 13.3% (476/3575) for installed DR systems. By combining RR measurement with workflow analysis, targets for technical and teaching interventions were identified. The interventions decreased the RR to 1.8% (81/4476) for portable CR and to 8.2% (306/3748) for installed DR.We found the RR of direct digital chest radiography to be significantly higher than that of computed chest radiography. We believe this is due to the ease with which repeat images can be obtained and discarded, and it suggests the need for ongoing surveillance of RR. We were able to demonstrate that strategies to lower the RR, which had been developed in the era of film-based imaging, can be adapted to the digital environment. On the basis of our findings, we encourage radiologists to assess their own departmental RRs for direct digital chest radiography and to consider similar interventions if necessary to achieve acceptable RRs for this modality.

    View details for DOI 10.1097/RTI.0b013e3182455f36

    View details for Web of Science ID 000303066500010

    View details for PubMedID 22331101

  • Ligation of the Jugular Veins Does Not Result in Brain Inflammation or Demyelination in Mice PLOS ONE Atkinson, W., Forghani, R., Wojtkiewicz, G. R., Pulli, B., Iwamoto, Y., Ueno, T., Waterman, P., Truelove, J., Oklu, R., Chen, J. W. 2012; 7 (3): e33671


    An alternative hypothesis has been proposed implicating chronic cerebrospinal venous insufficiency (CCSVI) as a potential cause of multiple sclerosis (MS). We aimed to evaluate the validity of this hypothesis in a controlled animal model. Animal experiments were approved by the institutional animal care committee. The jugular veins in SJL mice were ligated bilaterally (n = 20), and the mice were observed for up to six months after ligation. Sham-operated mice (n = 15) and mice induced with experimental autoimmune encephalomyelitis (n = 8) were used as negative and positive controls, respectively. The animals were evaluated using CT venography and (99m)Tc-exametazime to assess for structural and hemodynamic changes. Imaging was performed to evaluate for signs of blood-brain barrier (BBB) breakdown and neuroinflammation. Flow cytometry and histopathology were performed to assess inflammatory cell populations and demyelination. There were both structural changes (stenosis, collaterals) in the jugular venous drainage and hemodynamic disturbances in the brain on Tc99m-exametazime scintigraphy (p = 0.024). In the JVL mice, gadolinium MRI and immunofluorescence imaging for barrier molecules did not reveal evidence of BBB breakdown (p = 0.58). Myeloperoxidase, matrix metalloproteinase, and protease molecular imaging did not reveal signs of increased neuroinflammation (all p>0.05). Flow cytometry and histopathology also did not reveal increase in inflammatory cell infiltration or population shifts. No evidence of demyelination was found, and the mice remained without clinical signs. Despite the structural and hemodynamic changes, we did not identify changes in the BBB permeability, neuroinflammation, demyelination, or clinical signs in the JVL group compared to the sham group. Therefore, our murine model does not support CCSVI as a cause of demyelinating diseases such as multiple sclerosis.

    View details for DOI 10.1371/journal.pone.0033671

    View details for Web of Science ID 000303857100035

    View details for PubMedID 22457780

    View details for PubMedCentralID PMC3310075

  • Evaluating the safety and effectiveness of percutaneous acetabuloplasty JOURNAL OF NEUROINTERVENTIONAL SURGERY Gupta, A. C., Hirsch, J. A., Chaudhry, Z. A., Chandra, R. V., Pulli, B., Galinsky, J. G., Hirsch, A. E., Yoo, A. J. 2012; 4 (2): 134-138


    To evaluate the safety and effectiveness of percutaneous acetabuloplasty in treating the pain and disability related to metastatic lesions of the acetabulum.This institutional review board approved retrospective study examined 11 patients who underwent percutaneous acetabuloplasty in our hospital from April 2007 to June 2010. All patients gave informed consent prior to the procedure, and all records were HIPAA compliant. Chart review was performed to collect patient demographics and to assess pre- and post-treatment patient performance on the Visual Analog Scale, Functional Mobility Scale and Analgesic Scale. Paired testing comparing the pre- and post-treatment scores for each patient was performed using the Wilcoxon signed rank test.There were 11 procedures: 10 performed under CT guidance and one using fluoroscopic guidance. There was a statistically significant decrease in patient Visual Analog Scale score (p=0.001) and Functional Mobility Scale score (p=0.03) after treatment. There was no change in median Analgesic Scale scores pre- and post-treatment although paired testing revealed a trend towards reduced analgesic use postoperatively (p=0.06). There were no clinically significant complications in this series.Percutaneous acetabuloplasty appears to be safe and effective for improving the pain and decreased mobility secondary to metastatic lesions of the acetabulum.

    View details for DOI 10.1136/jnis.2011.004879

    View details for Web of Science ID 000300216600018

    View details for PubMedID 21990476

  • Acute Ischemic Stroke: Infarct Core Estimation on CT Angiography Source Images Depends on CT Angiography Protocol RADIOLOGY Pulli, B., Schaefer, P. W., Hakimelahi, R., Chaudhry, Z. A., Lev, M. H., Hirsch, J. A., Gonzalez, R., Yoo, A. J. 2012; 262 (2): 593-604


    To test whether the relationship between acute ischemic infarct size on concurrent computed tomographic (CT) angiography source images and diffusion-weighted (DW) magnetic resonance images is dependent on the parameters of CT angiography acquisition protocols.This retrospective study had institutional review board approval, and all records were HIPAA compliant. Data in 100 patients with anterior-circulation acute ischemic stroke and large vessel occlusion who underwent concurrent CT angiography and DW imaging within 9 hours of symptom onset were analyzed. Measured areas of hyperintensity at acute DW imaging were used as the standard of reference for infarct size. Information regarding lesion volumes and CT angiography protocol parameters was collected for each patient. For analysis, patients were divided into two groups on the basis of CT angiography protocol differences (patients in group 1 were imaged with the older, slower protocol). Intermethod agreement for infarct size was evaluated by using the Wilcoxon signed rank test, as well as by using Spearman correlation and Bland-Altman analysis. Multivariate analysis was performed to identify predictors of marked (≥20%) overestimation of infarct size on CT angiography source images.In group 1 (n=35), median hypoattenuation volumes on CT angiography source images were slightly underestimated compared with DW imaging hyperintensity volumes (33.0 vs 41.6 mL, P=.01; ratio=0.83), with high correlation (ρ=0.91). In group 2 (n=65), median volume on CT angiography source images was much larger than that on DW images (94.8 vs 17.8 mL, P<.0001; ratio=3.5), with poor correlation (ρ=0.49). This overestimation on CT angiography source images would have inappropriately excluded from reperfusion therapy 44.4% or 90.3% of patients eligible according to DW imaging criteria on the basis of a 100-mL absolute threshold or a 20% or greater mismatch threshold, respectively. Atrial fibrillation and shorter time from contrast material injection to image acquisition were independent predictors of marked (≥20%) infarct size overestimation on CT angiography source images.CT angiography protocol changes designed to speed imaging and optimize arterial opacification are associated with significant overestimation of infarct size on CT angiography source images.

    View details for DOI 10.1148/radiol.11110896

    View details for Web of Science ID 000300300200027

    View details for PubMedID 22187626

    View details for PubMedCentralID PMC3267077

  • Imaging-based treatment selection for intravenous and intra-arterial stroke therapies: a comprehensive review EXPERT REVIEW OF CARDIOVASCULAR THERAPY Yoo, A. J., Pulli, B., Gonzalez, R. 2011; 9 (7): 857-876


    Reperfusion therapy is the only approved treatment for acute ischemic stroke. The current approach to patient selection is primarily based on the time from stroke symptom onset. However, this algorithm sharply restricts the eligible patient population, and neglects large variations in collateral circulation that ultimately determine the therapeutic time window in individual patients. Time alone is unlikely to remain the dominant parameter. Alternative approaches to patient selection involve advanced neuroimaging methods including MRI diffusion-weighted imaging, magnetic resonance and computed tomography perfusion imaging and noninvasive angiography that provide potentially valuable information regarding the state of the brain parenchyma and the neurovasculature. These techniques have now been used extensively, and there is emerging evidence on how specific imaging data may result in improved clinical outcomes. This article will review the major studies that have investigated the role of imaging in patient selection for both intravenous and intra-arterial therapies.

    View details for DOI 10.1586/ERC.11.56

    View details for Web of Science ID 000216606000011

    View details for PubMedID 21809968

    View details for PubMedCentralID PMC3162247

  • Semiautomated Fluoroscopy Radiation Dose Capture and Reporting AMERICAN JOURNAL OF ROENTGENOLOGY Pulli, B., Fintelmann, F., Liu, B., Rosenthal, D. I. 2010; 195 (5): 1180-1182


    This article describes a semiautomated system for the capture and reporting of fluoroscopic dose data in a large radiology department. By use of a novel Web-based interface, dose data are entered by technologists at the time of examination, and radiology reports are populated automatically.Dose data were successfully captured in 94% of 5,914 reports generated over the course of 6 months. Missing data were attributed to system malfunction (9.5%) and human error (90.5%) and could be reconstructed by quality control measurements in most instances.

    View details for DOI 10.2214/AJR.09.4162

    View details for Web of Science ID 000283295300033

    View details for PubMedID 20966325