Publications by authors named "Ronald Wolf"

124 Publications

Cerebrovascular Reactivity Mapping Made Simpler: A Pragmatic Approach for the Clinic and Laboratory.

Radiology 2021 Mar 9:210165. Epub 2021 Mar 9.

From the Department of Radiology, University of Pennsylvania Perelman School of Medicine, 3400 Spruce St, Philadelphia, PA 19104.

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http://dx.doi.org/10.1148/radiol.2021210165DOI Listing
March 2021

Effective and safe use of alitretinoin after acitretin failure in oral lichen planus.

Dermatol Ther 2020 11 2;33(6):e14441. Epub 2020 Nov 2.

Department of Dermatology and Allergology, Ludwig-Maximilian University Munich, Munich, Germany.

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http://dx.doi.org/10.1111/dth.14441DOI Listing
November 2020

Coronavirus Disease (COVID-19)-Related Disseminated Leukoencephalopathy: A Retrospective Study of Findings on Brain MRI.

AJR Am J Roentgenol 2021 04 17;216(4):1046-1047. Epub 2021 Feb 17.

Department of Radiology, Division of Neuroradiology, Perelman School of Medicine at the University of Pennsylvania, 3400 Spruce St, Philadelphia, PA 19104.

Among 2820 inpatients with coronavirus disease (COVID-19), 59 (2.1%) underwent brain MRI. Of them, six (10.2%) had MRI findings suspicious for COVID-19-related disseminated leukoencephalopathy (CRDL), which is characterized by extensive confluent or multifocal white matter lesions (with characteristics and locations atypical for other causes), microhemorrhages, diffusion restriction, and enhancement. CRDL is an uncommon but important differential consideration in patients with neurologic manifestations of COVID-19.
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http://dx.doi.org/10.2214/AJR.20.24364DOI Listing
April 2021

Pearls & Oy-sters: Bilateral globus pallidus lesions in a patient with COVID-19.

Neurology 2020 09 25;95(10):454-457. Epub 2020 Jun 25.

From the Department of Neurology (C.V.K.-S., J.L.M., A.R., M.A.G., B.L.C., K.A.D.), Department of Radiology (R.L.W., S.M., J.M.S., J.H.M., J.W.L.), Division of Pulmonary, Allergy, and Critical Care (D.G.D., J.E.M.), and Division of Infectious Diseases (M.Z.D., R.N.E.), Perelman School of Medicine at the University of Pennsylvania; and Division of Neurology (J.L.M.), the Children's Hospital of Philadelphia, PA.

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http://dx.doi.org/10.1212/WNL.0000000000010157DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7538218PMC
September 2020

Freewater estimatoR using iNtErpolated iniTialization (FERNET): Characterizing peritumoral edema using clinically feasible diffusion MRI data.

PLoS One 2020 29;15(5):e0233645. Epub 2020 May 29.

DiCIPHR (Diffusion and Connectomics in Precision Healthcare Research) Lab, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States of America.

Characterization of healthy versus pathological tissue in the peritumoral area is confounded by the presence of edema, making free water estimation the key concern in modeling tissue microstructure. Most methods that model tissue microstructure are either based on advanced acquisition schemes not readily available in the clinic or are not designed to address the challenge of edema. This underscores the need for a robust free water elimination (FWE) method that estimates free water in pathological tissue but can be used with clinically prevalent single-shell diffusion tensor imaging data. FWE in single-shell data requires the fitting of a bi-compartment model, which is an ill-posed problem. Its solution requires optimization, which relies on an initialization step. We propose a novel initialization approach for FWE, FERNET, which improves the estimation of free water in edematous and infiltrated peritumoral regions, using single-shell diffusion MRI data. The method has been extensively investigated on simulated data and healthy dataset. Additionally, it has been applied to clinically acquired data from brain tumor patients to characterize the peritumoral region and improve tractography in it.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0233645PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7259683PMC
August 2020

Eine Reisedermatose mit Spätfolgen: marine Kontaktdermatitis durch Korallen mit verzögerter lichenoider Reaktion.

J Dtsch Dermatol Ges 2020 May;18(5):495-497

Klinik für Dermatologie und Allergologie, Universitätsklinikum Gießen und Marburg, Philipps Universität Marburg, Marburg.

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http://dx.doi.org/10.1111/ddg.14086_gDOI Listing
May 2020

Focused Ultrasound Thalamotomy with Dentato-Rubro-Thalamic Tractography in Patients with Spinal Cord Stimulators and Cardiac Pacemakers.

Stereotact Funct Neurosurg 2020 13;98(4):263-269. Epub 2020 May 13.

Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Magnetic resonance image-guided high-intensity focused ultrasound (MRgFUS)-based thermal ablation of the ventral intermediate nucleus of the thalamus (VIM) is a minimally invasive treatment modality for essential tremor (ET). Dentato-rubro-thalamic tractography (DRTT) is becoming increasingly popular for direct targeting of the presumed VIM ablation focus. It is currently unclear if patients with implanted pulse generators (IPGs) can safely undergo MRgFUS ablation and reliably acquire DRTT suitable for direct targeting. We present an 80-year-old male with a spinal cord stimulator (SCS) and an 88-year-old male with a cardiac pacemaker who both underwent MRgFUS for medically refractory ET. Clinical outcomes were measured using the Clinical Rating Scale for Tremor (CRST). DRTT was successfully created and imaging parameter adjustments did not result in any delay in procedural time in either case. In the first case, 7 therapeutic sonications were delivered. The patient improved immediately and durably with a 90% CRST-disability improvement at 6-week follow-up. In our second case, 6 therapeutic sonications were delivered with durable, 75% CRST-disability improvement at 6 weeks. These are the first cases of MRgFUS thalamotomy in patients with IPGs. DRTT targeting and MRgFUS-based thermal ablation can be safely performed in these patients using a 1.5-T MRI.
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http://dx.doi.org/10.1159/000507031DOI Listing
May 2020

Travel-associated dermatosis with late sequelae: Coral contact dermatitis presenting with a lichenoid reaction.

J Dtsch Dermatol Ges 2020 May 20;18(5):493-495. Epub 2020 Apr 20.

Department of Dermatology and Allergology, University Medical Center of Giessen and Marburg, Philipps University, Marburg, Germany.

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http://dx.doi.org/10.1111/ddg.14086DOI Listing
May 2020

Emerging Techniques in Imaging of Glioma Microenvironment.

Top Magn Reson Imaging 2020 Apr;29(2):103-114

Department of Radiology, Hospital of University of Pennsylvania, Perelman School of Medicine of the University of Pennsylvania, Philadelphia, PA.

Magnetic resonance imaging (MRI) has been the cornerstone of imaging of brain tumors in the past 4 decades. Conventional MRI remains the workhorse for neuro-oncologic imaging, not only for basic information such as location, extent, and navigation but also able to provide information regarding proliferation and infiltration, angiogenesis, hemorrhage, and more. More sophisticated MRI sequences have extended the ability to assess and quantify these features; for example, permeability and perfusion acquisitions can assess blood-brain barrier disruption and angiogenesis, diffusion techniques can assess cellularity and infiltration, and spectroscopy can address metabolism. Techniques such as fMRI and diffusion fiber tracking can be helpful in diagnostic planning for resection and radiation therapy, and more sophisticated iterations of these techniques can extend our understanding of neurocognitive effects of these tumors and associated treatment responses and effects. More recently, MRI has been used to go beyond such morphological, physiological, and functional characteristics to assess the tumor microenvironment. The current review highlights multiple recent and emerging approaches in MRI to characterize the tumor microenvironment.
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http://dx.doi.org/10.1097/RMR.0000000000000232DOI Listing
April 2020

Update: MRI in Malignant Glioma.

Authors:
Ronald L Wolf

Top Magn Reson Imaging 2020 04;29(2):69

Perelman School of Medicine, University of Pennsylvania Health System, Department of Radiology, Neuroradiology Section, Philadelphia, PA.

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http://dx.doi.org/10.1097/RMR.0000000000000236DOI Listing
April 2020

Imaging and histopathologic correlates of plasma cell-free DNA concentration and circulating tumor DNA in adult patients with newly diagnosed glioblastoma.

Neurooncol Adv 2020 Jan-Dec;2(1):vdaa016. Epub 2020 Feb 27.

Glioblastoma Translational Center of Excellence, Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Background: Plasma cell-free DNA (cfDNA) concentration is lower in glioblastoma (GBM) compared to other solid tumors, which can lead to low circulating tumor DNA (ctDNA) detection. In this study, we investigated the relationship between multimodality magnetic resonance imaging (MRI) and histopathologic features with plasma cfDNA concentration and ctDNA detection in patients with treatment-naive GBM.

Methods: We analyzed plasma cfDNA concentration, MRI scans, and tumor histopathology from 42 adult patients with newly diagnosed GBM. Linear regression analysis was used to examine the relationship of plasma cfDNA concentration before surgery to imaging and histopathologic characteristics. In a subset of patients, imaging and histopathologic metrics were also compared between patients with and without a detected tumor somatic mutation.

Results: Tumor volume with elevated (>1.5 times contralateral white matter) rate transfer constant (, a surrogate of blood-brain barrier [BBB] permeability) was independently associated with plasma cfDNA concentration ( = .001). Histopathologic characteristics independently associated with plasma cfDNA concentration included CD68+ macrophage density ( = .01) and size of tumor vessels ( = .01). Patients with higher (grade ≥3) perivascular CD68+ macrophage density had lower volume transfer constant (, = .01) compared to those with lower perivascular CD68+ macrophage density. Detection of at least 1 somatic mutation in plasma cfDNA was associated with significantly lower perivascular CD68+ macrophages ( = .01).

Conclusions: Metrics of BBB disruption and quantity and distribution of tumor-associated macrophages are associated with plasma cfDNA concentration and ctDNA detection in GBM patients. These findings represent an important step in understanding the factors that determine plasma cfDNA concentration and ctDNA detection.
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http://dx.doi.org/10.1093/noajnl/vdaa016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7045782PMC
February 2020

Histopathology-validated machine learning radiographic biomarker for noninvasive discrimination between true progression and pseudo-progression in glioblastoma.

Cancer 2020 06 4;126(11):2625-2636. Epub 2020 Mar 4.

Center for Biomedical Image Computing and Analytics, University of Pennsylvania, Philadelphia, Pennsylvania.

Background: Imaging of glioblastoma patients after maximal safe resection and chemoradiation commonly demonstrates new enhancements that raise concerns about tumor progression. However, in 30% to 50% of patients, these enhancements primarily represent the effects of treatment, or pseudo-progression (PsP). We hypothesize that quantitative machine learning analysis of clinically acquired multiparametric magnetic resonance imaging (mpMRI) can identify subvisual imaging characteristics to provide robust, noninvasive imaging signatures that can distinguish true progression (TP) from PsP.

Methods: We evaluated independent discovery (n = 40) and replication (n = 23) cohorts of glioblastoma patients who underwent second resection due to progressive radiographic changes suspicious for recurrence. Deep learning and conventional feature extraction methods were used to extract quantitative characteristics from the mpMRI scans. Multivariate analysis of these features revealed radiophenotypic signatures distinguishing among TP, PsP, and mixed response that compared with similar categories blindly defined by board-certified neuropathologists. Additionally, interinstitutional validation was performed on 20 new patients.

Results: Patients who demonstrate TP on neuropathology are significantly different (P < .0001) from those with PsP, showing imaging features reflecting higher angiogenesis, higher cellularity, and lower water concentration. The accuracy of the proposed signature in leave-one-out cross-validation was 87% for predicting PsP (area under the curve [AUC], 0.92) and 84% for predicting TP (AUC, 0.83), whereas in the discovery/replication cohort, the accuracy was 87% for predicting PsP (AUC, 0.84) and 78% for TP (AUC, 0.80). The accuracy in the interinstitutional cohort was 75% (AUC, 0.80).

Conclusion: Quantitative mpMRI analysis via machine learning reveals distinctive noninvasive signatures of TP versus PsP after treatment of glioblastoma. Integration of the proposed method into clinical studies can be performed using the freely available Cancer Imaging Phenomics Toolkit.
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http://dx.doi.org/10.1002/cncr.32790DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7893811PMC
June 2020

Thalamic Deep Brain Stimulation for Essential Tremor: Relation of the Dentatorubrothalamic Tract with Stimulation Parameters.

World Neurosurg 2020 05 16;137:e89-e97. Epub 2020 Jan 16.

Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA. Electronic address:

Background: In deep brain stimulation (DBS) for essential tremor, the primary target ventrointermedius (VIM) nucleus cannot be clearly visualized with structural imaging. As such, there has been much interest in the dentatorubrothalamic tract (DRTT) for target localization, but evidence for the DRTT as a putative stimulation target in tremor suppression is lacking. We evaluated proximity of the DRTT in relation to DBS stimulation parameters.

Methods: This is a retrospective analysis of 26 consecutive patients who underwent DBS with microelectrode recordings (46 leads). Fiber tracking was performed with a published deterministic technique. Clinically optimized stimulation parameters were obtained in all patients at the time of most recent follow-up (6.2 months). Volume of tissue activated (VTA) around contacts was calculated from a published model.

Results: Tremor severity was reduced in all treated hemispheres, with 70% improvement in the treated hand score of the Clinical Rating Scale for Tremor. At the level of the active contact (2.9 ± 2.0 mm superior to the commissural plane), the center of the DRTT was lateral to the contacts (5.1 ± 2.1 mm). The nearest fibers of the DRTT were 2.4 ± 1.7 mm from the contacts, whereas the radius of the VTA was 2.9 ± 0.7 mm. The VTA overlapped with the DRTT in 77% of active contacts. The distance from active contact to the DRTT was positively correlated with stimulation voltage requirements (Kendall τ = 0.33, P = 0.006), whereas distance to the atlas-based VIM coordinates was not.

Conclusions: Active contacts in proximity to the DRTT had lower voltage requirements. Data from a large cohort provide support for the DRTT as an effective stimulation target for tremor control.
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http://dx.doi.org/10.1016/j.wneu.2020.01.039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7584387PMC
May 2020

Epidermal overexpression of LRIG1 disturbs development and homeostasis in skin by disrupting the ERBB system.

J Dermatol Sci 2019 Dec 21;96(3):185-188. Epub 2019 Nov 21.

Institute of Molecular Animal Breeding and Biotechnology, Gene Center, LMU München, Munich, Germany. Electronic address:

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http://dx.doi.org/10.1016/j.jdermsci.2019.11.007DOI Listing
December 2019

The transmembrane protein LRIG2 increases tumor progression in skin carcinogenesis.

Mol Oncol 2019 11 21;13(11):2476-2492. Epub 2019 Oct 21.

Institute of Molecular Animal Breeding and Biotechnology, Gene Center, LMU München, Germany.

Over the last few decades, the number of cases of non-melanoma skin cancer (NMSC) has risen to over 3 million cases every year worldwide. Members of the ERBB receptor family are important regulators of skin development and homeostasis and, when dysregulated, contribute to skin pathogenesis. In this study, we investigated leucine-rich repeats and immunoglobulin-like domains 2 (LRIG2), a transmembrane protein involved in feedback loop regulation of the ERBB receptor family during NMSC. LRIG2 was identified to be up-regulated in various types of squamous cell carcinoma (SCC), but little is known about LRIG2 in cutaneous SCC (cSCC). To investigate the function of LRIG2 in cSCC in vivo, we generated a skin-specific LRIG2 overexpressing transgenic mouse line (LRIG2-TG) using the Tet-Off system. We employed the 7,12-dimethylbenz(a)anthracene/12-O-tetra-decanoylphorbol-13-acetate (DMBA/TPA) two-stage chemical carcinogenesis model and analyzed the skin during homeostasis and tumorigenesis. LRIG2-TG mice did not exhibit alterations in skin development or homeostasis but showed an interaction between LRIG2 and thrombospondin-1, which is often involved in angiogenesis and tumorigenesis. However, during carcinogenesis, transgenic animals showed significantly increased tumor progression and a more rapid development of cSCC. This was accompanied by changes in the ERBB system. After a single TPA application, inflammation of the epidermis was enhanced during LRIG2 overexpression. In human skin samples, LRIG2 expression was identified in the basal layer of the epidermis and in hair follicles of normal skin, but also in cSCC samples. In conclusion, epidermal LRIG2 excess is associated with activated EGFR/ERBB4-MAPK signaling and accelerated tumor progression in experimentally induced NMSC, suggesting LRIG2 as a potential oncoprotein in skin.
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http://dx.doi.org/10.1002/1878-0261.12579DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6822252PMC
November 2019

Hepatoportal Venous Trauma: Analysis of Incidence, Morbidity, and Mortality.

Vasc Endovascular Surg 2020 Jan 30;54(1):36-41. Epub 2019 Sep 30.

University of California, Irvine Medical Center, Orange, CA, USA.

Objectives: Although traumatic injuries to the superior mesenteric vein (SMV), portal vein (PV), and hepatic vein (HV) are rare, their impact is significant. Small single center reports estimate mortality rates ranging from 29% to 100%. Our aim is to elucidate the incidence and outcomes associated with each injury due to unique anatomic positioning and varied tolerance of ligation. We hypothesize that SMV injury is associated with a lower risk of mortality compared to HV and PV injury in adult trauma patients.

Methods: The Trauma Quality Improvement Program database (2010-2016) was queried for patients with injury to either the SMV, PV, or HV. A multivariable logistic regression model was used for analysis.

Results: From 1,403,466 patients, 966 (0.07%) had a single major hepatoportal venous injury with 460 (47.6%) involving the SMV, 281 (29.1%) involving the PV, and 225 (23.3%) involving the HV. There was no difference in the percentage of patients undergoing repair or ligation between SMV, PV, and HV injuries ( > .05). Compared to those with PV and HV injuries, patients with SMV injury had a higher rate of concurrent bowel resection (38.5% vs 12.1% vs 7.6%, < .001) and lower mortality (33.3% vs 45.9% vs 49.3%, < .01). After controlling for covariates, traumatic SMV injury increased the risk of mortality (odds ratio [OR] 1.59, confidence interval [CI] = 1.00-2.54, = .05) in adult trauma patients; however, this was less than PV injury (OR = 2.77, CI = 1.56-4.93, = .001) and HV injury (OR = 2.70, CI = 1.46-4.99, = .002).

Conclusion: Traumatic SMV injury had a lower rate of mortality compared to injuries of the HV and PV. SMV injury increased the risk of mortality by 60% in adult trauma patients, whereas PV and HV injuries nearly tripled the risk of mortality.
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http://dx.doi.org/10.1177/1538574419878577DOI Listing
January 2020

Neuroimaging Findings in US Government Personnel With Possible Exposure to Directional Phenomena in Havana, Cuba.

JAMA 2019 Jul;322(4):336-347

Department of Neurosurgery, University of Pennsylvania, Perelman School of Medicine, Philadelphia.

Importance: United States government personnel experienced potential exposures to uncharacterized directional phenomena while serving in Havana, Cuba, from late 2016 through May 2018. The underlying neuroanatomical findings have not been described.

Objective: To examine potential differences in brain tissue volume, microstructure, and functional connectivity in government personnel compared with individuals not exposed to directional phenomena.

Design, Setting, And Participants: Forty government personnel (patients) who were potentially exposed and experienced neurological symptoms underwent evaluation at a US academic medical center from August 21, 2017, to June 8, 2018, including advanced structural and functional magnetic resonance imaging analytics. Findings were compared with imaging findings of 48 demographically similar healthy controls.

Exposures: Potential exposure to uncharacterized directional phenomena of unknown etiology, manifesting as pressure, vibration, or sound.

Main Outcomes And Measures: Potential imaging-based differences between patients and controls with regard to (1) white matter and gray matter total and regional brain volumes, (2) cerebellar tissue microstructure metrics (eg, mean diffusivity), and (3) functional connectivity in the visuospatial, auditory, and executive control subnetworks.

Results: Imaging studies were completed for 40 patients (mean age, 40.4 years; 23 [57.5%] men; imaging performed a median of 188 [range, 4-403] days after initial exposure) and 48 controls (mean age, 37.6 years; 33 [68.8%] men). Mean whole brain white matter volume was significantly smaller in patients compared with controls (patients: 542.22 cm3; controls: 569.61 cm3; difference, -27.39 [95% CI, -37.93 to -16.84] cm3; P < .001), with no significant difference in the whole brain gray matter volume (patients: 698.55 cm3; controls: 691.83 cm3; difference, 6.72 [95% CI, -4.83 to 18.27] cm3; P = .25). Among patients compared with controls, there were significantly greater ventral diencephalon and cerebellar gray matter volumes and significantly smaller frontal, occipital, and parietal lobe white matter volumes; significantly lower mean diffusivity in the inferior vermis of the cerebellum (patients: 7.71 × 10-4 mm2/s; controls: 8.98 × 10-4 mm2/s; difference, -1.27 × 10-4 [95% CI, -1.93 × 10-4 to -6.17 × 10-5] mm2/s; P < .001); and significantly lower mean functional connectivity in the auditory subnetwork (patients: 0.45; controls: 0.61; difference, -0.16 [95% CI, -0.26 to -0.05]; P = .003) and visuospatial subnetwork (patients: 0.30; controls: 0.40; difference, -0.10 [95% CI, -0.16 to -0.04]; P = .002) but not in the executive control subnetwork (patients: 0.24; controls: 0.25; difference: -0.016 [95% CI, -0.04 to 0.01]; P = .23).

Conclusions And Relevance: Among US government personnel in Havana, Cuba, with potential exposure to directional phenomena, compared with healthy controls, advanced brain magnetic resonance imaging revealed significant differences in whole brain white matter volume, regional gray and white matter volumes, cerebellar tissue microstructural integrity, and functional connectivity in the auditory and visuospatial subnetworks but not in the executive control subnetwork. The clinical importance of these differences is uncertain and may require further study.
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http://dx.doi.org/10.1001/jama.2019.9269DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6652163PMC
July 2019

Arterial Spin Labeling and Dynamic Susceptibility Contrast-enhanced MR Imaging for evaluation of arteriovenous shunting and tumor hypoxia in glioblastoma.

Sci Rep 2019 06 19;9(1):8747. Epub 2019 Jun 19.

Department of Radiology, Hospital of University of Pennsylvania, Perelman School of Medicine of the University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Glioblastoma (GBM) is the most common primary malignant brain tumor in adults and carries a dismal prognosis. Significant challenges in the care of patients with GBM include marked vascular heterogeneity and arteriovenous (AV) shunting, which results in tumor hypoxia and inadequate delivery of systemic treatments to reach tumor cells. In this study, we investigated the utility of different MR perfusion techniques to detect and quantify arteriovenous (AV) shunting and tumor hypoxia in patients with GBM. Macrovascular shunting was present in 33% of subjects, with the degree of shunting ranging from (37-60%) using arterial spin labeling perfusion. Among the dynamic susceptibility contrast-enhanced perfusion curve features, there were a strong negative correlation between hypoxia score, DSC perfusion curve recovery slope (r = -0.72, P = 0.018) and angle (r = -0.73, P = 0.015). The results of this study support the possibility of using arterial spin labeling and pattern analysis of dynamic susceptibility contrast-enhanced MR Imaging for evaluation of arteriovenous shunting and tumor hypoxia in glioblastoma.
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http://dx.doi.org/10.1038/s41598-019-45312-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6584644PMC
June 2019

Koebnerisin (S100A15): A novel player in the pathogenesis of rosacea.

J Am Acad Dermatol 2019 06;80(6):1753-1755

Department of Dermatology and Allergology, Ludwig Maximilian University Munich, Munich, Germany. Electronic address:

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http://dx.doi.org/10.1016/j.jaad.2018.06.012DOI Listing
June 2019

Perioperative blood transfusion is associated with an increased risk for post-surgical infection following pancreaticoduodenectomy.

HPB (Oxford) 2019 11 27;21(11):1577-1584. Epub 2019 Apr 27.

Department of Surgery, University of California Irvine Medical Center, Orange, CA, United States.

Background/purpose: Perioperative blood transfusion is common after pancreaticoduodenectomy (PD) and may predispose patients to infectious complications. The purpose of this study is to examine the association between perioperative blood transfusion and the development of post-surgical infection after PD.

Methods: Patients who underwent PD from 2014 to 2015 were identified in the NSQIP pancreas-specific database. Logistic regression analysis was used to compute adjusted odds ratios (aOR) to identify an independent association between perioperative red blood cell transfusion (within 72 h of surgery) and the development of post-operative infection after 72 h.

Results: A total of 6869 patients underwent PD during this time period. Of these, 1372 (20.0%) patients received a perioperative blood transfusion. Patients receiving transfusion had a higher rate of post-operative infection (34.7% vs 26.5%, p < 0.001). After adjusting for significant covariates, perioperative transfusion was independently associated the subsequent development of any post-operative infection (aOR 1.41 [1.23-1.62], p < 0.001), including pneumonia (aOR 2.01 [1.48-2.74], p < 0.001), sepsis (aOR 1.62 [1.29-2.04], p < 0.001), and septic shock (aOR 1.92 [1.38-2.68], p < 0.001).

Conclusion: There is a strong independent association between perioperative blood transfusion and the development of subsequent post-operative infection following PD.
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http://dx.doi.org/10.1016/j.hpb.2019.03.374DOI Listing
November 2019

Focused Ultrasound Thalamotomy for Essential Tremor in the Setting of a Ventricular Shunt: Technical Report.

Oper Neurosurg (Hagerstown) 2019 10;17(4):376-381

Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.

Background: A recent randomized controlled trial of magnetic resonance imaging (MRI)-guided focused ultrasound (FUS) for essential tremor (ET) demonstrated safety and efficacy. Patients with ventricular shunts may be good candidates for FUS to minimize hardware-associated infections.

Objective: To demonstrate feasibility of FUS in this subset of patients.

Methods: A 74-yr-old male with medically refractory ET, and a right-sided ventricular shunt for normal pressure hydrocephalus, underwent FUS to the right ventro-intermedius (VIM) nucleus. The VIM nucleus was directly targeted using deterministic tractography. Clinical outcomes were measured using the Clinical Rating Scale for Tremor.

Results: Shunt components required 6% of the total ultrasound transducer elements to be shut off. Eight therapeutic sonications were delivered (maximum temperature, 64°), leading to a 90% improvement in hand tremor and a 100% improvement in functional disability at the 3-mo follow-up. No complications were noted.

Conclusion: This is the first case of FUS thalamotomy in a patient with a shunt. Direct VIM targeting and achievement of therapeutic temperatures with acoustic energy is feasible in this subset of patients.
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http://dx.doi.org/10.1093/ons/opz013DOI Listing
October 2019

Three-dimensional echo planar spectroscopic imaging for differentiation of true progression from pseudoprogression in patients with glioblastoma.

NMR Biomed 2019 02 17;32(2):e4042. Epub 2018 Dec 17.

Department of Radiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.

Accurate differentiation of true progression (TP) from pseudoprogression (PsP) in patients with glioblastomas (GBMs) is essential for planning adequate treatment and for estimating clinical outcome measures and future prognosis. The purpose of this study was to investigate the utility of three-dimensional echo planar spectroscopic imaging (3D-EPSI) in distinguishing TP from PsP in GBM patients. For this institutional review board approved and HIPAA compliant retrospective study, 27 patients with GBM demonstrating enhancing lesions within six months of completion of concurrent chemo-radiation therapy were included. Of these, 18 were subsequently classified as TP and 9 as PsP based on histological features or follow-up MRI studies. Parametric maps of choline/creatine (Cho/Cr) and choline/N-acetylaspartate (Cho/NAA) were computed and co-registered with post-contrast T -weighted and FLAIR images. All lesions were segmented into contrast enhancing (CER), immediate peritumoral (IPR), and distal peritumoral (DPR) regions. For each region, Cho/Cr and Cho/NAA ratios were normalized to corresponding metabolite ratios from contralateral normal parenchyma and compared between TP and PsP groups. Logistic regression analyses were performed to obtain the best model to distinguish TP from PsP. Significantly higher Cho/NAA was observed from CER (2.69 ± 1.00 versus 1.56 ± 0.51, p = 0.003), IPR (2.31 ± 0.92 versus 1.53 ± 0.56, p = 0.030), and DPR (1.80 ± 0.68 versus 1.19 ± 0.28, p = 0.035) regions in TP patients compared with those with PsP. Additionally, significantly elevated Cho/Cr (1.74 ± 0.44 versus 1.34 ± 0.26, p = 0.023) from CER was observed in TP compared with PsP. When these parameters were incorporated in multivariate regression analyses, a discriminatory model with a sensitivity of 94% and a specificity of 87% was observed in distinguishing TP from PsP. These results indicate the utility of 3D-EPSI in differentiating TP from PsP with high sensitivity and specificity.
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http://dx.doi.org/10.1002/nbm.4042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6519064PMC
February 2019

MRI of Recurrent Glioblastoma: Reliability and Reality.

Authors:
Ronald L Wolf

Radiology 2019 02 27;290(2):477-478. Epub 2018 Nov 27.

From the Department of Radiology, Neuroradiology Section, Perelman School of Medicine, University of Pennsylvania Health System, Dulles 219, 3400 Spruce St, Philadelphia, PA 19104.

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http://dx.doi.org/10.1148/radiol.2018182530DOI Listing
February 2019

Multiparametric magnetic resonance imaging in the assessment of anti-EGFRvIII chimeric antigen receptor T cell therapy in patients with recurrent glioblastoma.

Br J Cancer 2019 01 27;120(1):54-56. Epub 2018 Nov 27.

Department of Radiology, Division of Neuroradiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.

EGFRvIII targeted chimeric antigen receptor T (CAR-T) cell therapy has recently been reported for treating glioblastomas (GBMs); however, physiology-based MRI parameters have not been evaluated in this setting. Ten patients underwent multiparametric MRI at baseline, 1, 2 and 3 months after CAR-T therapy. Logistic regression model derived progression probabilities (PP) using imaging parameters were used to assess treatment response. Four lesions from "early surgery" group demonstrated high PP at baseline suggestive of progression, which was confirmed histologically. Out of eight lesions from remaining six patients, three lesions with low PP at baseline remained stable. Two lesions with high PP at baseline were associated with large decreases in PP reflecting treatment response, whereas other two lesions with high PP at baseline continued to demonstrate progression. One patient didn't have baseline data but demonstrated progression on follow-up. Our findings indicate that multiparametric MRI may be helpful in monitoring CAR-T related early therapeutic changes in GBM patients.
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http://dx.doi.org/10.1038/s41416-018-0342-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6325110PMC
January 2019

Association of Immunologic Markers With Survival in Upfront Resectable Pancreatic Cancer.

JAMA Surg 2018 11;153(11):1055-1057

Integrated Therapies Laboratory, Earle A. Chiles Research Institute, Providence Portland Medical Center, Portland, Oregon.

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http://dx.doi.org/10.1001/jamasurg.2018.1757DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6583701PMC
November 2018

Differentiation of brain infection from necrotic glioblastoma using combined analysis of diffusion and perfusion MRI.

J Magn Reson Imaging 2019 01 20;49(1):184-194. Epub 2018 Apr 20.

Department of Radiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Background: Accurate differentiation of brain infections from necrotic glioblastomas (GBMs) may not always be possible on morphologic MRI or on diffusion tensor imaging (DTI) and dynamic susceptibility contrast perfusion-weighted imaging (DSC-PWI) if these techniques are used independently.

Purpose: To investigate the combined analysis of DTI and DSC-PWI in distinguishing brain injections from necrotic GBMs.

Study Type: Retrospective.

Population: Fourteen patients with brain infections and 21 patients with necrotic GBMs.

Field Strength/sequence: 3T MRI, DTI, and DSC-PWI.

Assessment: Parametric maps of mean diffusivity (MD), fractional anisotropy (FA), coefficient of linear (CL), and planar anisotropy (CP) and leakage corrected cerebral blood volume (CBV) were computed and coregistered with postcontrast T -weighted and FLAIR images. All lesions were segmented into the central core and enhancing region. For each region, median values of MD, FA, CL, CP, relative CBV (rCBV), and top 90 percentile of rCBV (rCBV ) were measured.

Statistical Tests: All parameters from both regions were compared between brain infections and necrotic GBMs using Mann-Whitney tests. Logistic regression analyses were performed to obtain the best model in distinguishing these two conditions.

Results: From the central core, significantly lower MD (0.90 × 10  ± 0.44 × 10 mm /s vs. 1.66 × 10  ± 0.62 × 10 mm /s, P = 0.001), significantly higher FA (0.15 ± 0.06 vs. 0.09 ± 0.03, P < 0.001), and CP (0.07 ± 0.03 vs. 0.04 ± 0.02, P = 0.009) were observed in brain infections compared to those in necrotic GBMs. Additionally, from the contrast-enhancing region, significantly lower rCBV (1.91 ± 0.95 vs. 2.76 ± 1.24, P = 0.031) and rCBV (3.46 ± 1.41 vs. 5.89 ± 2.06, P = 0.001) were observed from infective lesions compared to necrotic GBMs. FA from the central core and rCBV from enhancing region provided the best classification model in distinguishing brain infections from necrotic GBMs, with a sensitivity of 91% and a specificity of 93%.

Data Conclusion: Combined analysis of DTI and DSC-PWI may provide better performance in differentiating brain infections from necrotic GBMs.

Level Of Evidence: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:184-194.
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http://dx.doi.org/10.1002/jmri.26053DOI Listing
January 2019

Prognostic value of contrast enhancement and FLAIR for survival in newly diagnosed glioblastoma treated with and without bevacizumab: results from ACRIN 6686.

Neuro Oncol 2018 09;20(10):1400-1410

Department of Radiology, Duke University Medical Center, Durham, North Carolina.

Background: ACRIN 6686/RTOG 0825 was a phase III trial of conventional chemoradiation plus adjuvant temozolomide with bevacizumab or without (placebo) in newly diagnosed glioblastoma. This study investigated whether changes in contrast-enhancing and fluid attenuated inversion recovery (FLAIR)-hyperintense tumor assessed by central reading prognosticate overall survival (OS).

Methods: Two hundred eighty-four patients (171 men; median age 57 y, range 19-79; 159 on bevacizumab) had MRI at post-op (baseline) and pre-cycle 4 of adjuvant temozolomide (22 wk post chemoradiation initiation). Four central readers measured bidimensional lesion enhancement (2D-T1) and FLAIR hyperintensity at both time points. Changes from baseline to pre-cycle 4 for both markers were dichotomized (increasing vs non-increasing). Cox proportional hazards model and Kaplan-Meier survival estimates were used for inference.

Results: Adjusting for treatment, increasing 2D-T1 (n = 262, hazard ratio [HR] = 2.07, 95% CI: 1.48-2.91, P < 0.0001) and FLAIR (n = 273, HR = 1.75, 95% CI: 1.26-2.41, P = 0.0008) significantly predicted worse OS. Median OS (days) was significantly shorter for patients with increasing versus non-increasing 2D-T1 for both bevacizumab (443 vs 535, P = 0.004) and placebo (526 vs 887, P = 0.001). Median OS was significantly shorter for patients with increasing versus non-increasing FLAIR for placebo (595 vs 872, P = 0.001), and trended similarly for bevacizumab (499 vs 535, P = 0.0935). Adjusting for 2D-T1 and treatment, increasing FLAIR represented significantly higher risk for death (HR = 1.59 [1.11-2.26], P = 0.01).

Conclusion: Increased 2D-T1 significantly predicts worse OS in both treatment groups, implying absence of a substantial proportion of pseudoprogression 22 weeks after initiation of standard therapy. FLAIR adds value beyond 2D-T1 in predicting OS, potentially addressing the pseudoresponse effect by substratifying bevacizumab-treated patients with non-increasing 2D-T1.
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http://dx.doi.org/10.1093/neuonc/noy049DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6120359PMC
September 2018

Neurological Manifestations Among US Government Personnel Reporting Directional Audible and Sensory Phenomena in Havana, Cuba.

JAMA 2018 03;319(11):1125-1133

Center for Brain Injury and Repair, University of Pennsylvania, Philadelphia.

Importance: From late 2016 through August 2017, US government personnel serving on diplomatic assignment in Havana, Cuba, reported neurological symptoms associated with exposure to auditory and sensory phenomena.

Objective: To describe the neurological manifestations that followed exposure to an unknown energy source associated with auditory and sensory phenomena.

Design, Setting, And Participants: Preliminary results from a retrospective case series of US government personnel in Havana, Cuba. Following reported exposure to auditory and sensory phenomena in their homes or hotel rooms, the individuals reported a similar constellation of neurological symptoms resembling brain injury. These individuals were referred to an academic brain injury center for multidisciplinary evaluation and treatment.

Exposures: Report of experiencing audible and sensory phenomena emanating from a distinct direction (directional phenomena) associated with an undetermined source, while serving on US government assignments in Havana, Cuba, since 2016.

Main Outcomes And Measures: Descriptions of the exposures and symptoms were obtained from medical record review of multidisciplinary clinical interviews and examinations. Additional objective assessments included clinical tests of vestibular (dynamic and static balance, vestibulo-ocular reflex testing, caloric testing), oculomotor (measurement of convergence, saccadic, and smooth pursuit eye movements), cognitive (comprehensive neuropsychological battery), and audiometric (pure tone and speech audiometry) functioning. Neuroimaging was also obtained.

Results: Of 24 individuals with suspected exposure identified by the US Department of State, 21 completed multidisciplinary evaluation an average of 203 days after exposure. Persistent symptoms (>3 months after exposure) were reported by these individuals including cognitive (n = 17, 81%), balance (n = 15, 71%), visual (n = 18, 86%), and auditory (n = 15, 68%) dysfunction, sleep impairment (n = 18, 86%), and headaches (n = 16, 76%). Objective findings included cognitive (n = 16, 76%), vestibular (n = 17, 81%), and oculomotor (n = 15, 71%) abnormalities. Moderate to severe sensorineural hearing loss was identified in 3 individuals. Pharmacologic intervention was required for persistent sleep dysfunction (n = 15, 71%) and headache (n = 12, 57%). Fourteen individuals (67%) were held from work at the time of multidisciplinary evaluation. Of those, 7 began graduated return to work with restrictions in place, home exercise programs, and higher-level work-focused cognitive rehabilitation.

Conclusions And Relevance: In this preliminary report of a retrospective case series, persistent cognitive, vestibular, and oculomotor dysfunction, as well as sleep impairment and headaches, were observed among US government personnel in Havana, Cuba, associated with reports of directional audible and/or sensory phenomena of unclear origin. These individuals appeared to have sustained injury to widespread brain networks without an associated history of head trauma.
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http://dx.doi.org/10.1001/jama.2018.1742DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5885885PMC
March 2018

Wolf's isotopic response: Lichen planus patterns on non-segmental muco-cutaneous vitiligo.

Eur J Dermatol 2018 04;28(2):229-230

Department of Dermatology and Allergology, Ludwig-Maximilian University Munich, Munich, Germany, Department of Dermatology and Allergology, Philipps University Marburg, Marburg, Germany.

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http://dx.doi.org/10.1684/ejd.2017.3208DOI Listing
April 2018