May 2020Safety and Efficacy of VB-111, an Anticancer Gene Therapy, in Patients with Recurrent Glioblastoma: Results of a Phase I/II Study.
Brenner AJ, Peters KB, Vredenburgh J, Bokstein F, Blumenthal DT, Yust-Katz S, Peretz I, Oberman B, Freedman LS, Ellingson BM, Cloughesy TF, Sher N, Cohen YC, Lowenton-Spier N, Rachmilewitz Minei T, Yakov N, Mendel I, Breitbart E, Wen PY.
BACKGROUND: VB-111 is a non-replicating adenovirus carrying a Fas-chimera transgene, leading to targeted apoptosis of tumor vascular endothelium and induction of a tumor-specific immune response. This phase I/II study evaluated the safety, tolerability, and efficacy of VB-111 with and without bevacizumab in recurrent glioblastoma (rGBM). METHODS: Patients with rGBM (n = 72) received VB-111 in 4 treatment groups: subtherapeutic (VB-111 dose escalation), limited exposure (LE; VB-111 monotherapy until progression), primed combination (VB-111 monotherapy continued upon progression with combination of bevacizumab), and unprimed combination (upfront combination of VB-111 and bevacizumab). The primary endpoint was median overall survival (OS). Secondary endpoints were safety, overall response rate, and progression-free survival (PFS).
May 2020Integration of Chest CT CAD into the Clinical Workflow and Impact on Radiologist Efficiency.
Brown M, Browning P, Wahi-Anwar MW, Murphy M, Delgado J, Greenspan H, Abtin F, Ghahremani S, Yaghmai N, da Costa I, Becker M, Goldin J.
RATIONALE AND OBJECTIVES: The purpose of this paper is to describe the integration of a commercial chest CT computer-aided detection (CAD) system into the clinical radiology reporting workflow and perform an initial investigation of its impact on radiologist efficiency. It seeks to complement research into CAD sensitivity and specificity of stand-alone systems, by focusing on report generation time when the CAD is integrated into the clinical workflow. MATERIALS AND METHODS: A commercial chest CT CAD software that provides automated detection and measurement of lung nodules, ascending and descending aorta, and pleural effusion was integrated with a commercial radiology report dictation application. The CAD system automatically prepopulated a radiology report template, thus offering the potential for increased efficiency. The integrated system was evaluated using 40 scans from a publicly available lung nodule database. Each scan was read using two methods: (1) without CAD analytics, i.e., manually populated report with measurements using electronic calipers, and (2) with CAD analytics to prepopulate the report for reader review and editing. Three radiologists participated as readers in this study.
May 2020Diffusion MRI Changes in the Anterior Subventricular Zone Following Chemoradiation in Glioblastoma with Posterior Ventricular Involvement.
Cho N, Wang C, Raymond C, Kaprealian T, Ji M, Salamon N, Pope WB, Nghiemphu PL, Lai A, Cloughesy TF, Ellingson BM.
INTRODUCTION: There is growing evidence that the subventricular zone (SVZ) plays a key role in glioblastoma (GBM) tumorigenesis. However, little is known regarding how the SVZ, which is a harbor for adult neural stem cells, may be influenced by chemoradiation. The current diffusion-weighted imaging (DWI) study explored ipsilateral and contralateral alterations in the anterior SVZ in GBM patients with posterior enhancing lesions following chemoradiation. METHODS: Forty GBM patients with tumor involvement in the posterior SVZ (mean age = 57 ± 10; left-hemisphere N = 25; right-hemisphere N = 15) were evaluated using DWI before and after chemoradiation. Regions-of-interest were drawn on the ipsilesional and contralesional anterior SVZ on apparent diffusion coefficient (ADC) maps for both timepoints. ADC histogram analysis was performed by modeling a bimodal, double Gaussian distribution to obtain ADCL, defined as the mean of the lower Gaussian distribution.
May 2020A Randomized Controlled Phase III Study of VB-111 Combined with Bevacizumab vs Bevacizumab Monotherapy in Patients with Recurrent Glioblastoma (GLOBE).
Cloughesy TF, Brenner A, de Groot JF, Butowski NA, Zach L, Campian JL, Ellingson BM, Freedman LS, Cohen YC, Lowenton-Spier N, Rachmilewitz Minei T, Fain Shmueli S; GLOBE Study Investigators , Patrick Y W.
BACKGROUND: Ofranergene obadenovec (VB-111) is an anticancer viral therapy that demonstrated in a phase II study a survival benefit for patients with recurrent glioblastoma (rGBM) who were primed with VB-111 monotherapy that was continued after progression with concomitant bevacizumab. METHODS: This pivotal phase III randomized, controlled trial compared the efficacy and safety of upfront combination of VB-111 and bevacizumab versus bevacizumab monotherapy. Patients were randomized 1:1 to receive VB-111 1013 viral particles every 8 weeks in combination with bevacizumab 10 mg/kg every 2 weeks (combination arm) or bevacizumab monotherapy (control arm). The primary endpoint was overall survival (OS), and secondary endpoints were objective response rate (ORR) by Response Assessment in Neuro-Oncology (RANO) criteria and progression-free survival (PFS).
May 2020ACR Appropriateness Criteria® Primary Bone Tumors.
Expert Panel on Musculoskeletal Imaging, Bestic JM, Wessell DE, Beaman FD, Cassidy RC, Czuczman GJ, Demertzis JL, Lenchik L, Motamedi K, Pierce JL, Sharma A, Sloan AE, Than K, Walker EA, Ying-Kou Yung E, Kransdorf MJ.
Although primary bone tumors are relatively uncommon, appropriate imaging evaluation is essential when they are suspected or incidentally detected. In almost all cases, radiographs are the most appropriate initial imaging study for screening and characterization of primary bone tumors. Radiographs often provide sufficient information for diagnosis and to guide the treating clinician. However, when conventional radiographs alone are inadequate, they still often guide the selection of the most appropriate next step for advanced imaging. MRI and CT are typically the most appropriate next step. MRI provides excellent soft-tissue contrast allowing for evaluation of the tissue composition (such as fat, hemorrhage, fluid levels) and anatomic extent of bone tumors. CT provides complementary information, with its ability to detect subtle matrix mineralization or periosteal reaction that may not be seen on radiographs or MRI. This publication focuses on six common variants to guide diagnosis and management of primary bone tumors. In addition to conventional radiographs, appropriate use of MRI, CT, PET/CT, bone scan, and ultrasound are discussed. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.
May 2020Microneedle Drug Eluting Balloon for Enhanced Drug Delivery to Vascular Tissue.
Lee K, Lee J, Lee SG, Park S, Yang DS, Lee JJ, Khademhosseini A, Kim JS, Ryu W.
High rates of restenosis and neointimal formation have driven increasing interest in the application of drug eluting balloons (DEB) as counteractive measures for intraluminal drug delivery. The use of DEBs eliminates the need for stents so that serious side effects including in-stent restenosis and stent thrombosis can be avoided and long-term medication of anti-platelet agent is not needed. Despite their benefits, DEBs have poor drug delivery efficiency due to short balloon inflation times (30-60 s) that limit the passive drug diffusion from the balloon surface to the luminal lesion. To increase drug delivery efficiency, a microneedle DEB (MNDEB) was developed by a conformal transfer molding process using a thin polydimethylsiloxane mold bearing a negative array of MNs of 200 μm in height. A MN array composed of UV curable resin was formed onto the surface of DEB, and drugs were coated onto the structure. The mechanical properties of the MN array were investigated and MN penetration into luminal vasculature was confirmed in vivo. An increase in drug delivery efficiency compared to a standard DEB was demonstrated in an in vivo test in a rabbit aorta. Finally, the superior therapeutic efficacy of MNDEBs was evaluated using an atherosclerosis rabbit model.
May 2020Ferrous Sulfate-directed Dual-cross-linked Hyaluronic Acid Hydrogels with Long-term Delivery of Donepezil.
Lee SY, Park JH, Yang M, Baek MJ, Kim MH, Lee J, Khademhosseini A, Kim DD, Cho HJ.
Ferrous sulfate (FeSO4)-directed dual-cross-linked hydrogels were designed for application in single-syringe injections. The use of FeSO4, rather than other iron salts, can modulate the gelation time and make it available for subcutaneous injection with a single syringe. These hydrogels are based on hyaluronic acid-dopamine (HA-dp) that contain donepezil (DPZ)-entrapping poly(lactic-co-glycolic acid) (PLGA) microsphere (MS). Although DPZ has been administered orally, its sustained release formulation via subcutaneous injection may reduce the dosing frequency for patients with Alzheimer's disease. The HA-dp conjugate was synthesized via an amide bond reaction for coordination of dp with a metal ion (Fe2+ or Fe3+) and self-polymerization of dp. The HA-dp/DPZ-loaded PLGA MS (PD MS)/FeSO4 gel system was considerably hardened via both the coordination of the metal ion with HA-dp and covalent bonding of dp. In addition, a quick restoration of the collapsed gel structure and sustained DPZ release from the HA-dp/PD MS/FeSO4 structure were achieved. The pharmacokinetic parameters after its subcutaneous injection in a rat indicate the sustained release and absorption of DPZ from the HA-dp/PD MS/FeSO4 system. The proposed system can be prepared by a simple method and can be efficiently and safely used for the long-term delivery of DPZ after the subcutaneous injection.
May 2020State of the Art: Toward Improving Outcomes of Lung and Liver Tumor Biopsies in Clinical Trials-A Multidisciplinary Approach.
Levy EB, Fiel MI, Hamilton SR, Kleiner DE, McCall SJ, Schirmacher P, Travis W, Kuo MD, Suh RD, Tam AL, Islam SU, Ferry-Galow K, Enos RA, Doroshow JH, Makhlouf HR.
PURPOSE: National Cancer Institute (NCI)-sponsored clinical trial network studies frequently require biopsy specimens for pharmacodynamic and molecular biomarker analyses, including paired pre- and post-treatment samples. The purpose of this meeting of NCI-sponsored investigators was to identify local institutional standard procedures found to ensure quantitative and qualitative specimen adequacy. METHODS: NCI convened a conference on best biopsy practices, focusing on the clinical research community. Topics discussed were (1) criteria for specimen adequacy in the personalized medicine era, (2) team-based approaches to ensure specimen adequacy and quality control, and (3) risk considerations relevant to academic and community practitioners and their patients.
May 202024/7/365 Neuroradiologist Coverage Improves Resident Perception of Educational Experience, Referring Physician Satisfaction, and Turnaround Time.
Spitler K, Vijayasarathi A, Salehi B, Dua S, Azizyan A, Cekic M, Yaghmai N, Homer R, Salamon N.
PURPOSE: To quantitatively and qualitatively assess the impact of attending neuroradiology coverage on radiology resident perceptions of the on-call experience, referring physician satisfaction, and final report turnaround times. MATERIALS AND METHODS: 24/7/365 attending neuroradiologist coverage began in October 2016 at our institution. In March 2017, an online survey of referring physicians, (emergency medicine, neurosurgery, and stroke neurology) and radiology residents was administered at a large academic medical center. Referring physicians were queried regarding their perceptions of patient care, report accuracy, timeliness, and availability of attending radiologists before and after the implementation of overnight neuroradiology coverage. Radiology residents were asked about their level of independence, workload, and education while on-call. Turnaround time (TAT) was measured over a 5-month period before and after the implementation of overnight neuroradiology coverage.
May 2020Engineering Tough, Injectable, Naturally Derived, Bioadhesive Composite Hydrogels.
Tavafoghi M, Sheikhi A, Tutar R, Jahangiry J, Baidya A, Haghniaz R, Khademhosseini A.
Engineering mechanically robust bioadhesive hydrogels that can withstand large strains may open new opportunities for the sutureless sealing of highly stretchable tissues. While typical chemical modifications of hydrogels, such as increasing the functional group density of crosslinkable moieties and blending them with other polymers or nanomaterials have resulted in improved mechanical stiffness, the modified hydrogels have often exhibited increased brittleness resulting in deteriorated sealing capabilities under large strains. Furthermore, highly elastic hydrogels, such as tropoelastin derivatives are highly expensive. Here, gelatin methacryloyl (GelMA) is hybridized with methacrylate-modified alginate (AlgMA) to enable ion-induced reversible crosslinking that can dissipate energy under strain. The hybrid hydrogels provide a photocrosslinkable, injectable, and bioadhesive platform with an excellent toughness that can be tailored using divalent cations, such as calcium. This class of hybrid biopolymers with more than 600% improved toughness compared to GelMA may set the stage for durable, mechanically resilient, and cost-effective tissue sealants. This strategy to increase the toughness of hydrogels may be extended to other crosslinkable polymers with similarly reactive moieties.
May 2020Influence of the Location and Zone of Tumor in Prostate Cancer Detection and Localization on 3-T Multiparametric MRI Based on PI-RADS Version 2.
Wibulpolprasert P, Raman SS, Hsu W, Margolis DJA, Asvadi NH, Khoshnoodi P, Moshksar A, Tan N, Ahuja P, Maehara CK, Sisk A, Sayre J, Lu DSK, Reiter RE.
OBJECTIVE. The objective of our study was to determine the performance of 3-T multiparametric MRI (mpMRI) for prostate cancer (PCa) detection and localization, stratified by anatomic zone and level, using Prostate Imaging Reporting and Data System version 2 (PI-RADSv2) and whole-mount histopathology (WMHP) as reference. MATERIALS AND METHODS. Multiparametric MRI examinations of 415 consecutive men were compared with thin-section WMHP results. A genitourinary radiologist and pathologist collectively determined concordance. Two radiologists assigned PI-RADSv2 scores and sector location to all detected foci by consensus. Tumor detection rates were calculated for clinical and pathologic (tumor location and zone) variables. Both rigid and adjusted sector-matching models were used to account for fixation-related issues.
May 2020Intermodality Feature Fusion Combining Unenhanced Computed Tomography and Ferumoxytol-enhanced Magnetic Resonance Angiography for Patient-specific Vascular Mapping in Renal Impairment.
Yoshida T, Nguyen KL, Shahrouki P, Quinones-Baldrich WJ, Lawrence PF, Finn JP.
OBJECTIVE: The purpose of this study was to establish the feasibility of fusing complementary, high-contrast features from unenhanced computed tomography (CT) and ferumoxytol-enhanced magnetic resonance angiography (FE-MRA) for preprocedural vascular mapping in patients with renal impairment. METHODSS: In this Institutional Review Board-approved and Health Insurance Portability and Accountability Act-compliant study, 15 consecutive patients underwent both FE-MRA and unenhanced CT scanning, and the complementary high-contrast features from both modalities were fused to form an integrated, multifeature image. Source images from CT and MRA were segmented and registered. To validate the accuracy, precision, and concordance of fused images to source images, unambiguous landmarks, such as wires from implantable medical devices or indwelling catheters, were marked on three-dimensional (3D) models of the respective modalities, followed by rigid co-registration, interactive fusion, and fine adjustment. We then compared the positional offsets using pacing wires or catheters in the source FE-MRA (defined as points of interest [POIs]) and fused images (n = 5 patients, n = 247 points). Points within 3D image space were referenced to the respective modalities: x (right-left), y (anterior-posterior), and z (cranial-caudal). The respective 3D orthogonal reference axes from both image sets were aligned, such that with perfect registration, a given point would have the same (x, y, z) component values in both sets. The 3D offsets (Δx mm, Δy mm, Δz mm) for each of the corresponding POIs represent nonconcordance between the source FE-MRA and fused images. The offsets were compared using concordance correlation coefficients. Interobserver agreement was assessed using intraclass correlation coefficients and Bland-Altman analyses.
May 2020Prostate Diffusion MRI with Minimal Echo Time Using Eddy Current Nulled Convex Optimized Diffusion Encoding.
Zhang Z, Moulin K, Aliotta E, Shakeri S, Afshari Mirak S, Hosseiny M, Raman S, Ennis DB, Wu HH.
BACKGROUND: Prostate diffusion-weighted imaging (DWI) using monopolar encoding is sensitive to eddy-current-induced distortion artifacts. Twice-refocused bipolar encoding suppresses eddy current artifacts, but increases echo time (TE), leading to lower signal-to-noise ratio (SNR). Optimization of the diffusion encoding might improve prostate DWI. PURPOSE: To evaluate eddy current nulled convex optimized diffusion encoding (ENCODE) for prostate DWI with minimal TE. STUDY TYPE: Prospective cohort study. POPULATION: A diffusion phantom, an ex vivo prostate specimen, 10 healthy male subjects (27 ± 3 years old), and five prostate cancer patients (62 ± 7 years old). FIELD STRENGTH/SEQUENCE: 3T; single-shot spin-echo echoplanar DWI. ASSESSMENT: Eddy-current artifacts, TE, SNR, apparent diffusion coefficient (ADC), and image quality scores from three independent readers were compared between monopolar, bipolar, and ENCODE prostate DWI for standard-resolution (1.6 × 1.6 mm2 , partial Fourier factor [pF] = 6/8) and higher-resolution protocols (1.6 × 1.6 mm2 , pF = off; 1.0 × 1.0 mm2 , pF = 6/8). STATISTICAL TESTING: SNR and ADC differences between techniques were tested with Kruskal-Wallis and Wilcoxon signed-rank tests (P < 0.05 considered significant).
April 2020Thinning or Dehiscence of Bone in Structures of the Middle Cranial Fossa Floor in Superior Semicircular Canal Dehiscence.
Arsenault JJ, Romiyo P, Miao T, Monteiro K, De Jong R, Kaur T, Johanis M, Duong C, Sheppard JP, Sun MZ, Ferraro R, Salamon N, Yang I, Gopen Q.
BACKGROUND: Superior semicircular canal dehiscence (SSCD) is a rare inner ear disorder; currently, it is unknown whether the etiopathology underlying this structural irregularity affects neighboring structures. The goal is to investigate the prevalence of bone thinning in areas of the middle cranial fossa (MCF) floor in SSCD and non-SSCD patients. METHODS: This retrospective study analyzed 100 patients from March 2011 to June 2017 at a tertiary referral center. 100 patients undergoing 118 SSCD repair surgeries (18 bilateral) were identified. 12 SSCD ears were excluded due to lack of pre-operative computed tomography (CT) scans or history of prior SSCD repair at an outside facility. Non-SSCD ears were identified from routinely-obtained CT scans for temporal bone fracture (fractured sides excluded) for a total of 101 ears; 26 non-SSCD ears were excluded due to lack of high-resolution imaging.
April 2020Obstructed Membranous Transformation of the Inferior Vena Cava in Patients with Hepatic Vein-type Budd-Chiari Syndrome: A Case Series.
Ding PX, Liu C, Han XW, Ding JY, Tse G, Lee EW.
Budd-Chiari syndrome (BCS) is a rare disease characterized by the obstruction of hepatic venous outflow due to occlusion of the hepatic vein (HV) or the inferior vena cava (IVC). The pathophysiology of IVC and HV membranous transformation, which can form in isolation or simultaneously, remains unclear in patients with combined-type BCS. Here we report three cases of patients with BCS demonstrating conversion from HV-type to combined-type. Three patients with only HV-type BCS underwent percutaneous balloon angioplasty (PTA) of the obstructed HV. During follow up, membranous transformation of the IVC was observed. This condition was subsequently treated with PTA of the IVC. These cases demonstrate that HV-type BCS may convert to combined-type BCS.
April 2020An Electronic Form for Reporting Results of Targeted Prostate Biopsy: Urology Integrated Diagnostic Report (Uro-IDR).
Guorgui J, Kinnaird A, Jayadevan R, Priester AM, Arnold CW, Marks LS.
OBJECTIVE: To detail the development of an electronic report that graphically conveys all relevant information from targeted prostate biopsy. METHODS: The Urology Integrated Diagnostic Report (Uro-IDR) is based on a published framework (RadPath) which enables the compilation of diagnostic data from urology, radiology, and pathology. Each component of the Uro-IDR is generated by the contributing clinician, is assembled in one document, and provides correlation of the 3 inputs at a glance. Upon completion, the Uro-IDR is automatically linked to the electronic medical record as an interactive file and can also be downloaded for offline sharing as a PDF.
April 2020Existence of a Dose-Length Effect in Spinal Nerves Receiving Single-Session Stereotactic Ablative Radiation Therapy.
Hrycushko B, van der Kogel AJ, Phillips L, Folkert M, Sayre JW, Vernino S, Hassan-Rezaeian N, Foster RD, Yamada Y, Timmerman R, Medin PM.
PURPOSE: The spinal nerves have been observed to have a similar single-session dose tolerance to that of the spinal cord in pigs. Small-animal studies have shown that spinal cord dose tolerance depends on the length irradiated. This work aims to determine whether a dose-length effect exists for spinal nerves. METHODS AND MATERIALS: Twenty-seven Yucatan minipigs underwent computed tomography and magnetic resonance imaging for treatment planning, followed by single-session stereotactic ablative radiation therapy. A 0.5 cm length of the left-sided C6, C7, and C8 spinal nerves was targeted. The pigs were distributed into 6 groups with prescription doses of 16 Gy (n = 5), 18 Gy (n = 5), 20 Gy (n = 5), 22 Gy (n = 5), 24 Gy (n = 5), or 36 Gy (n = 2) and corresponding maximum doses of 16.7, 19.1, 21.3, 23.1, 25.5, and 38.6 Gy, respectively. Neurologic status was assessed with a serial electrodiagnostic examination and daily observation of gait for approximately 52 weeks. A histopathologic examination of paraffin-embedded sections with Luxol fast blue/periodic acid-Schiff's staining was also performed.
April 2020Updated 10-year Outcomes of Percutaneous Radiofrequency Ablation as First-line Therapy for Single Hepatocellular Carcinoma < 3 cm: Emphasis on Association of Local Tumor Progression and Overall Survival.
Lee MW, Kang D, Lim HK, Cho J, Sinn DH, Kang TW, Song KD, Rhim H, Cha DI, Lu DSK.
OBJECTIVES: The purpose of this study was to evaluate the 10-year overall survival and local tumor progression (LTP) of percutaneous radiofrequency ablation (RFA) for single nodular hepatocellular carcinoma (HCC) < 3 cm using a large longitudinal hospital registry and clinical factors associated with overall survival and LTP. METHODS: A total of 467 newly diagnosed patients with single nodular HCC < 3 cm who underwent RFA as first-line therapy between January 2008 to December 2016 were analyzed. Overall survival and LTP were estimated using the Kaplan-Meier method. Cox regression and competing risks Cox regression analysis were performed to identify prognostic factors for overall survival and LTP, respectively.
April 2020Human Placenta Blood Flow During Early Gestation With Pseudocontinuous Arterial Spin Labeling MRI.
Liu D, Shao X, Danyalov A, Chanlaw T, Masamed R, Wang DJJ, Janzen C, Devaskar SU, Sung K.
BACKGROUND: Noninvasive measurement of placental blood flow is the major technical challenge for predicting ischemic placenta (IPD). Pseudocontinuous arterial spin labeling (pCASL) MRI was recently shown to be promising, but the potential value in predicting the subsequence development of IPD is not known. PURPOSE: To derive global and regional placental blood flow parameters from longitudinal measurements of pCASL MRI and to assess the associations between perfusion-related parameters and IPD. STUDY TYPE: Prospective. POPULATION: Eighty-four women completed two pCASL MRI scans (first; 14-18 weeks and second; 19-24 weeks) from prospectively recruited 118 subjects. A total of 69 subjects were included for the analysis, of which 15 subjects developed IPD. FIELD STRENGTH/SEQUENCE: 3T/T2 -weighted half-Fourier single-shot turbo spin-echo (HASTE) and pCASL. ASSESSMENT: Four perfusion-related parameters in the placenta were derived: placenta volume, placental blood flow (PBF), high PBF (hPBF), and relative hPBF. The longitudinal changes of the parameters and their association with IPD were tested after being normalizing to the 16th and 20th weeks of gestation. STATISTICAL TESTS: Comparisons between two gestational ages within subjects were performed using the paired Wilcoxon tests, and comparisons between normal and IPD groups were performed using the unpaired Wilcoxon tests.
April 2020MRI-guided Targeted Needle Placement During Motion Using Hydrostatic Actuators.
Mikaiel S, Simonelli J, Li X, Lee YH, Lee YS, Sung K, Lu DS, Tsao TC, Wu HH.
BACKGROUND: Magnetic resonance imaging (MRI) has unique advantages for guiding interventions, but the narrow space is a major challenge. This study evaluates the feasibility of a remote-controlled hydrostatic actuator system for MRI-guided targeted needle placement. METHODS: The effects of the hydrostatic actuator system on MR image quality were evaluated. Using a reference step-and-shoot method (SS) and the proposed actuator-assisted method (AA), two operators performed MRI-guided needle placement in targets (n = 12) in a motion phantom.
April 2020Stimuli-Responsive Delivery of Growth Factors for Tissue Engineering.
Qu M, Jiang X, Zhou X, Wang C, Wu Q, Ren L, Zhu J, Zhu S, Tebon P, Sun W, Khademhosseini A.
Growth factors (GFs) play a crucial role in directing stem cell behavior and transmitting information between different cell populations for tissue regeneration. However, their utility as therapeutics is limited by their short half-life within the physiological microenvironment and significant side effects caused by off-target effects or improper dosage. "Smart" materials that can not only sustain therapeutic delivery over a treatment period but also facilitate on-demand release upon activation are attracting significant interest in the field of GF delivery for tissue engineering. Three properties are essential in engineering these "smart" materials: 1) the cargo vehicle protects the encapsulated therapeutic; 2) release is targeted to the site of injury; 3) cargo release can be modulated by disease-specific stimuli. The aim of this review is to summarize the current research on stimuli-responsive materials as intelligent vehicles for controlled GF delivery; Five main subfields of tissue engineering are discussed: skin, bone and cartilage, muscle, blood vessel, and nerve. Challenges in achieving such "smart" materials and perspectives on future applications of stimuli-responsive GF delivery for tissue regeneration are also discussed.
April 2020A Novel Anthropomorphic Multimodality Phantom for MRI-based Radiotherapy Quality Assurance Testing.
Singhrao K, Fu J, Wu HH, Hu P, Kishan AU, Chin RK, Lewis JH.
PURPOSE: Increased utilization of magnetic resonance imaging (MRI) in radiotherapy has caused a growing need for phantoms that provide tissue-like contrast in both computed tomography (CT) and MRI images. Such phantoms can be used to compare MRI-based processes with CT-based clinical standards. Here, we develop and demonstrate the clinical utility of a three-dimensional (3D)-printed anthropomorphic pelvis phantom containing materials capable of T1, T2, and electron density matching for a clinically relevant set of soft tissues and bone. METHODS: The phantom design was based on a male pelvic anatomy template with thin boundaries separating tissue types. Slots were included to allow insertion of various dosimeters. The phantom structure was created using a 3D printer. The tissue compartments were filled with carrageenan-based materials designed to match the T1 and T2 relaxation times and electron densities of the corresponding tissues. CT and MRI images of the phantom were acquired and used to compare phantom T1 and T2 relaxation times and electron densities to literature-reported values for human tissue. To demonstrate clinical utility, the phantom was used for end-to-end testing of an MRI-only treatment simulation and planning workflow. Based on a T2 -weighted MRI image, synthetic CT (sCT) images were created using a statistical decomposition algorithm (MRIPlanner, Spectronic Research AB, Sweden) and used for dose calculation of volumetric-modulated arc therapy (VMAT) and seven-field intensity-modulated radiation therapy (IMRT) prostate plans. The plans were delivered on a Truebeam STX (Varian Medical Systems, Palo Alto, CA), with film and a 0.3 cc ion chamber used to measure the delivered dose. Doses calculated on the CT and sCTs were compared using common dose volume histogram metrics.
April 2020First-in-Human Phase I Study to Evaluate the Brain-Penetrant PI3K/mTOR Inhibitor GDC-0084 in Patients with Progressive or Recurrent High-Grade Glioma.
Wen PY, Cloughesy TF, Olivero AG, Morrissey KM, Wilson TR, Lu X, Mueller LU, Coimbra AF, Ellingson BM, Gerstner E, Lee EQ, Rodon J.
PURPOSE: GDC-0084 is an oral, brain-penetrant small-molecule inhibitor of PI3K and mTOR. A first-in-human, phase I study was conducted in patients with recurrent high-grade glioma. PATIENTS AND METHODS: GDC-0084 was administered orally, once daily, to evaluate safety, pharmacokinetics (PK), and activity. Fluorodeoxyglucose-PET (FDG-PET) was performed to measure metabolic responses.
April 2020Gelatin Methacryloyl Microneedle Patches for Minimally Invasive Extraction of Skin Interstitial Fluid.
Zhu J, Zhou X, Kim HJ, Qu M, Jiang X, Lee K, Ren L, Wu Q, Wang C, Zhu X, Tebon P, Zhang S, Lee J, Ashammakhi N, Ahadian S, Dokmeci MR, Gu Z, Sun W, Khademhosseini A.
The extraction of interstitial fluid (ISF) from skin using microneedles (MNs) has attracted growing interest in recent years due to its potential for minimally invasive diagnostics and biosensors. ISF collection by absorption into a hydrogel MN patch is a promising way that requires the materials to have outstanding swelling ability. Here, a gelatin methacryloyl (GelMA) patch is developed with an 11 × 11 array of MNs for minimally invasive sampling of ISF. The properties of the patch can be tuned by altering the concentration of the GelMA prepolymer and the crosslinking time; patches are created with swelling ratios between 293% and 423% and compressive moduli between 3.34 MPa and 7.23 MPa. The optimized GelMA MN patch demonstrates efficient extraction of ISF. Furthermore, it efficiently and quantitatively detects glucose and vancomycin in ISF in an in vivo study. This minimally invasive approach of extracting ISF with a GelMA MN patch has the potential to complement blood sampling for the monitoring of target molecules from patients.
March 2020BRCA and Beyond: Comprehensive Image-rich Review of Hereditary Breast and Gynecologic Cancer Syndromes.
Chung SH, Woldenberg N, Roth AR, Masamed R, Conlon W, Cohen JG, Joines MM, Patel MK.
In addition to the well-characterized BRCA1 and BRCA2 hereditary breast and ovarian cancer syndromes, many other syndromes that are associated with genetic mutations predispose individuals to an increased risk of breast and gynecologic malignancies. Many mutated genes encode for tumor-suppressor products and are inherited in an autosomal dominant manner. Mutations markedly increase an individual's lifetime risk of cancers in different organ systems, depending on the associated syndrome. These syndromes include Lynch syndrome, the most common hereditary cause of endometrial cancer, and Peutz-Jeghers syndrome, which increases the risks of breast cancer, ovarian cancer, and cervical adenoma malignum. Li-Fraumeni syndrome and Cowden syndrome increase the risk of breast cancer, and Gorlin syndrome increases the risk of ovarian fibromas. With advances in genetic testing, clinicians' knowledge and awareness of the numerous additional genes associated with breast and ovarian cancers, such as ATM, CHEK2, and PALB2, are rapidly expanding. Radiologists have essential roles in patient management, which include developing optimal screening protocols for these patients and closely monitoring them for the development or recurrence of disease-specific malignancies. Radiologists' roles continue to increase and evolve as more mutations are identified and high-risk imaging screening recommendations expand to identify these patients. Understanding the epidemiologic, genetic, and pathophysiologic features and the cancers associated with these syndromes enables radiologists to appropriately contribute to patient management, ensure accurate and timely diagnosis, and make syndrome-specific imaging recommendations. ©RSNA, 2020.
March 2020A Case Report of a Novel Germline GNAS Mutation in Sonic Hedgehog Activated Medulloblastoma.
Crane JN, Chang VY, Yong WH, Salamon N; Hane Lee for UCLA Clinical Genomics Center, Kianmahd J, Dorrani N, Martinez-Agosto JA, Davidson TB.
Medulloblastoma is the most common malignant brain tumor of childhood. Our knowledge of medulloblastoma has been advanced by the study of genetic cancer predisposition syndromes, which are associated with approximately 6% of cases. We describe a case of a novel germline GNAS mutation in medulloblastoma, in accordance with the CARE guidelines.
March 2020Longitudinal MRI Findings in Patients with Newly Diagnosed Glioblastoma after Intraoperative Radiotherapy.
Förster A, Böhme J, Maros ME, Brehmer S, Seiz-Rosenhagen M, Hänggi D, Wenz F, Groden C, Pope WB, Giordano FA.
BACKGROUND AND PURPOSE: Post-radiation treatment effects (pseudoprogression/radionecrosis) may bias MRI-based tumor response evaluation. To understand these changes specifically after high doses of radiotherapy, we analyzed MRIs of patients enrolled in the INTRAGO study (NCT02104882), a phase I/II dose-escalation trial of intraoperative radiotherapy (20-40 Gy) in glioblastoma. METHODS: INTRAGO patients were evaluated and compared to control patients who received standard therapy with focus on contrast enhancement patterns/volume, T2 lesion volume, and mean rCBV.
March 2020Multi-scale Cellular Engineering: From Molecules to Organ-on-a-chip.
Huang NF, Chaudhuri O, Cahan P, Wang A, Engler AJ, Wang Y, Kumar S, Khademhosseini A, Li S.
Recent technological advances in cellular and molecular engineering have provided new insights into biology and enabled the design, manufacturing, and manipulation of complex living systems. Here, we summarize the state of advances at the molecular, cellular, and multi-cellular levels using experimental and computational tools. The areas of focus include intrinsically disordered proteins, synthetic proteins, spatiotemporally dynamic extracellular matrices, organ-on-a-chip approaches, and computational modeling, which all have tremendous potential for advancing fundamental and translational science. Perspectives on the current limitations and future directions are also described, with the goal of stimulating interest to overcome these hurdles using multi-disciplinary approaches.
March 2020Onset to Reperfusion Time as a Determinant of Outcomes Across a Wide Range of ASPECTS in Endovascular Thrombectomy: Pooled Analysis of the SWIFT, SWIFT PRIME, and STAR Studies.
Kim JT, Goyal M, Levy EI, Liebeskind D, Jahan R, Pereira VM, Gralla J, Bonafe A, Saver JL.
BACKGROUND: The time-benefit relationship of endovascular thrombectomy (EVT) according to the size of the core infarct has been incompletely explored in prior studies. We investigated whether established infarct core size on baseline imaging modifies the relationship between onset-to-reperfusion time (OTR) and functional outcomes in patients with acute ischemic stroke treated with EVT. METHODS: We analyzed a database containing individual patient data pooled from three prospective Solitaire stent retriever studies. The inclusion criteria were treatment with a Solitaire device and achievement of substantial reperfusion (modified Thrombolysis in Cerebral Infarction 2b-3). Main analyses were performed in patients with baseline Alberta Stroke Program Early CT Scores (ASPECTSs) of 7-10.
March 2020Tumescent Injections in Subcutaneous Pig Tissue Disperse Fluids Volumetrically and Maintain Elevated Local Concentrations of Additives for Several Hours, Suggesting a Treatment for Drug Resistant Wounds.
Koulakis JP, Rouch J, Huynh N, Wu HH, Dunn JCY, Putterman S.
PURPOSE: Bolus injection of fluid into subcutaneous tissue results in accumulation of fluid at the injection site. The fluid does not form a pool. Rather, the injection pressure forces the interstitial matrix to expand to accommodate the excess fluid in its volume, and the fluid becomes bound similar to that in a hydrogel. We seek to understand the properties and dynamics of externally tumesced (swollen) subcutaneous tissue as a first step in assessing whether tumescent antibiotic injections into wounds may provide a novel method of treatment. METHODS: Subcutaneous injections of saline are performed in live and dead pigs and the physical properties (volume, expansion ratio, residence time, apparent diffusion constant) of the resulting fluid deposits are observed with diffusion-weighted magnetic resonance imaging, computed tomography, and 3D scanning.
March 2020Detection of Acute Infarction on Non-Contrast-enhanced CT: Closing the Gap with MRI via Machine Learning.
Stroke is the leading cause of substantial disability and is the fifth leading cause of death in the United States, costing our health care system more than $20 billion per year. Over the past 5 years, the treatment of acute ischemic stroke has been revolutionized. The ability to offer reperfusion therapies to a broader population of patients with acute ischemic stroke is one of the greatest achievements of cerebrovascular medicine in recent years and was made possible in part by the effective use of pretreatment neuroimaging. One of the key variables to improve patient selection for reperfusion therapies is the estimation of the extent of early ischemic changes (ie, ischemic core) at pretreatment imaging.
March 2020Tumor Size Matters-Understanding Concomitant Tumor Immunity in the Context of Hypofractionated Radiotherapy with Immunotherapy.
Nesseler JP, Lee MH, Nguyen C, Kalbasi A, Sayre JW, Romero T, Nickers P, McBride WH, Schaue D.
The purpose of this study was to determine the dynamic contributions of different immune cell subsets to primary and abscopal tumor regression after hypofractionated radiation therapy (hRT) and the impact of anti-PD-1 therapy. A bilateral syngeneic FSA1 fibrosarcoma model was used in immunocompetent C3H mice, with delayed inoculation to mimic primary and microscopic disease. The effect of tumor burden on intratumoral and splenic immune cell content was delineated as a prelude to hRT on macroscopic T1 tumors with 3 fractions of 8 Gy while microscopic T2 tumors were left untreated. This was performed with and without systemic anti-PD-1.
March 2020Rate of Change in Maximum 18F-FDOPA PET Uptake and Non-enhancing Tumor Volume Predict Malignant Transformation and Overall Survival in Low-Grade Gliomas.
Oughourlian TC, Yao J, Schlossman J, Raymond C, Ji M, Tatekawa H, Salamon N, Pope WB, Czernin J, Nghiemphu PL, Lai A, Cloughesy TF, Ellingson BM.
PURPOSE: To examine whether the rate of change in maximum
March 2020Society of Interventional Radiology Position Statement on Endovascular Intervention for Trauma.
Padia SA, Ingraham CR, Moriarty JM, Wilkins LR, Bream PR Jr, Tam AL, Patel S, McIntyre L, Wolinsky PR, Hanks SE.
March 2020Electrochemical Cytosensors for Detection of Breast Cancer Cells.
Vajhadin F, Ahadian S, Travas-Sejdic J, Lee J, Mazloum-Ardakani M, Salvador J, Aninwene GE 2nd, Bandaru P, Sun W, Khademhossieni A.
Breast cancer is one of lethal cancers among women with its metastasis leading to cancer-related morbidity and mortality. Circulating tumor cells (CTCs) derived from a primary tumor can be detected in the venous blood of cancer patients. Monitoring CTCs in blood samples has increased exponentially over the past decades and holds great promise in the diagnosis and treatment of metastatic breast cancer. Electrochemical cytosensors, classified as a class of electrochemical biosensors for sensitive detection and enumeration of targeted cells with minimally invasive methods, have the advantages of electrochemical biosensors, such as simplicity, low cost, and low limit of detection. Here, we review recent progress in the detection of CTCs from breast cancer with a focus on electrochemical cytosensors. This review describes platforms benefiting from these cytosensors to identify cancerous breast cells. Furthermore, strategies for signal amplification and also generation of reusable electrochemical cytosensors are introduced. In addition, breast cancer markers and biorecognition elements for cell capturing are reviewed.
March 2020Unionizing Radiology: A Potential Response to Increasing Corporatization.
Recent work has highlighted the trend of consolidation within radiology and health care at large. Traditionally, the practice of radiology has been highly fragmented, organized into local and regional practices, owned by radiologists. In the past few years, there has been an increase in local practice acquisitions by corporate-, venture capital-, or private equity-backed national entities (NEs), described collectively herein as "corporatization."
March 2020High Throughput Image Labeling on Chest Computed Tomography by Deep Learning.
Wang X, Teng P, Ontiveros A, Goldin JG, Brown MS.
When mining image data from PACs or clinical trials or processing large volumes of data without curation, the relevant scans must be identified among irrelevant or redundant data. Only images acquired with appropriate technical factors, patient positioning, and physiological conditions may be applicable to a particular image processing or machine learning task. Automatic labeling is important to make big data mining practical by replacing conventional manual review of every single-image series. Digital imaging and communications in medicine headers usually do not provide all the necessary labels and are sometimes incorrect. We propose an image-based high throughput labeling pipeline using deep learning, aimed at identifying scan direction, scan posture, lung coverage, contrast usage, and breath-hold types. They were posed as different classification problems and some of them involved further segmentation and identification of anatomic landmarks. Images of different view planes were used depending on the specific classification problem. All of our models achieved accuracy > 99% on test set across different tasks using a research database from multicenter clinical trials.
March 2020Percutaneous Thermal Ablation of Subcapsular Hepatocellular Carcinomas: Influence of Tumor-surface Contact and Protrusion on Therapeutic Efficacy and Safety.
Worakitsitisatorn A, Lu DS, Lee MW, Asvadi NH, Moshksar A, Yuen AD, McWilliams J, Raman SS.
PURPOSE: To evaluate therapeutic efficacy and complication of percutaneous thermal ablation of subcapsular hepatocellular carcinomas (HCCs), and how these may be influenced by the degree of tumor to liver surface contact and tumor protrusion from liver surface. MATERIALS AND METHODS: Our retrospective study was approved by the Institutional Review Board. Between January 2006 and December 2013, 290 patients (82 women, 208 men; mean age, 64.5 years; range, 33-89 years) with 474 subcapsular (within 1 cm to the liver surface) HCCs (mean size, 23.7 mm; range, 6-71 mm) underwent percutaneous thermal ablation. The HCCs were divided into surface contact group (n = 243) and non-surface contact group (n = 231). The former was further subdivided into exophytic and non-exophytic HCCs. Technical success, primary technique efficacy, local tumor progression (LTP), and secondary technique efficacy rates were analyzed and compared by the chi-square test or Fisher exact test. Prognostic factors for LTP and secondary technique efficacy were assessed using the Cox regression model. Major complications were also assessed.
February 2020Assessment of Response to Neoadjuvant Therapy Using CT Texture Analysis in Patients With Resectable and Borderline Resectable Pancreatic Ductal Adenocarcinoma.
Borhani AA, Dewan R, Furlan A, Seiser N, Zureikat AH, Singhi AD, Boone B, Bahary N, Hogg ME, Lotze M, Iii HJZ, Tublin ME.
OBJECTIVE. The goal of this study was to assess the correlation between CT-derived texture features of pancreatic ductal adenocarcinoma (PDAC) and histologic and biochemical markers of response to neoadjuvant treatment as well as disease-free survival in patients with potentially resectable PDAC. SUBJECTS AND METHODS. Thirty-nine patients completed this prospective study protocol between November 2013 and December 2016. All patients received neoadjuvant chemotherapy, underwent surgical resection, and had histologic grading of tumor response. Similar CT protocol was used for all patients. Pancreatic (late arterial) phase of pre- and posttreatment CT scans were evaluated. Histogram analysis and spatial-band-pass filtration were used to extract textural features. Correlation between textural parameters, histologic response, biochemical response, and genetic mutations was assessed using Mann-Whitney test, chi-square analysis, and multivariate logistic regression. Association with disease-free survival was assessed using Kaplan-Meier method and Cox model.
February 2020Renal Denervation as Adjunctive Therapy to Cardiac Sympathetic Denervation for Ablation Refractory Ventricular Tachycardia.
Bradfield JS, Hayase J, Liu K, Moriarty J, Kee ST, Do D, Ajijola OA, Vaseghi M, Gima J, Sorg J, Cote S, Pavez G, Buch E, Khakpour H, Krokhaleva Y, Macias C, Fujimura O, Boyle NG, Shivkumar K.
BACKGROUND: Autonomic modulation is finding an increasing role in the treatment of ventricular arrhythmias. Renal denervation (RDN) has been described as a treatment modality for refractory ventricular tachycardia (VT) in case series. OBJECTIVE: The purpose of this study was to evaluate RDN as an adjunctive therapy to cardiac sympathetic denervation (CSD) for ablation refractory VT. METHODS: Patients who underwent RDN after radiofrequency ablation and CSD procedures at our center from 2012 to 2019 were evaluated.
February 2020Constraints in Estimating the Proton Density Fat Fraction.
Bydder M, Ghodrati V, Gao Y, Robson MD, Yang Y, Hu P.
The study evaluates four physically motivated constraints in the estimation of the proton density fat fraction (PDFF). Least squares approaches were developed for constraining the parameters in PDFF quantification based on the physics of magnetic resonance imaging. These were smooth fieldmap, smooth initial phase, nonnegative proton density and moderate R2✶ values. The constraints were evaluated in terms of their influence on the bias and standard deviation of the estimated parameters using numerical simulations and in vivo data acquired at 0.35 T. Results show that unconstrained least squares estimation is noisy and biased and that constraints can be effective at reducing both the standard deviation and bias.
February 20203D-Printed Ultra-Robust Surface-Doped Porous Silicone Sensors for Wearable Biomonitoring.
Davoodi E, Montazerian H, Haghniaz R, Rashidi A, Ahadian S, Sheikhi A, Chen J, Khademhosseini A, Milani AS, Hoorfar M, Toyserkani E.
Three-dimensional flexible porous conductors have significantly advanced wearable sensors and stretchable devices because of their specific high surface area. Dip coating of porous polymers with graphene is a facile, low cost, and scalable approach to integrate conductive layers with the flexible polymer substrate platforms; however, the products often suffer from nanoparticle delamination and overtime decay. Here, a fabrication scheme based on accessible methods and safe materials is introduced to surface-dope porous silicone sensors with graphene nanoplatelets. The sensors are internally shaped with ordered, interconnected, and tortuous internal geometries (i.e., triply periodic minimal surfaces) using fused deposition modeling (FDM) 3D-printed sacrificial molds. The molds were dip coated to transfer-embed graphene onto the silicone rubber (SR) surface. The presented procedure exhibited a stable coating on the porous silicone samples with long-term electrical resistance durability over ∼12 months period and high resistance against harsh conditions (exposure to organic solvents). Besides, the sensors retained conductivity upon severe compressive deformations (over 75% compressive strain) with high strain-recoverability and behaved robustly in response to cyclic deformations (over 400 cycles), temperature, and humidity. The sensors exhibited a gauge factor as high as 10 within the compressive strain range of 2-10%. Given the tunable sensitivity, the engineered biocompatible and flexible devices captured movements as rigorous as walking and running to the small deformations resulted by human pulse.
February 2020Engineering Biomaterials with Micro/Nanotechnologies for Cell Reprogramming.
Fang J, Hsueh YY, Soto J, Sun W, Wang J, Gu Z, Khademhosseini A, Li S.
Cell reprogramming is a revolutionized biotechnology that offers a powerful tool to engineer cell fate and function for regenerative medicine, disease modeling, drug discovery, and beyond. Leveraging advances in biomaterials and micro/nanotechnologies can enhance the reprogramming performance in vitro and in vivo through the development of delivery strategies and the control of biophysical and biochemical cues. In this review, we present an overview of the state-of-the-art technologies for cell reprogramming and highlight the recent breakthroughs in engineering biomaterials with micro/nanotechnologies to improve reprogramming efficiency and quality. Finally, we discuss future directions and challenges for reprogramming technologies and clinical translation.
February 2020Using Transitional Changes on High-Resolution Computed Tomography to Monitor the Impact of Cyclophosphamide or Mycophenolate Mofetil on Systemic Sclerosis-Related Interstitial Lung Disease.
Kim GHJ, Tashkin DP, Lo P, Brown MS, Volkmann ER, Gjertson DW, Khanna D, Elashoff RM, Tseng CH, Roth MD, Goldin JG.
OBJECTIVE: To examine changes in the extent of specific patterns of interstitial lung disease (ILD) as they transition from one pattern to another in response to immunosuppressive therapy in systemic sclerosis-related ILD (SSc-ILD). METHODS: We evaluated changes in the quantitative extent of specific lung patterns of ILD using volumetric high-resolution computed tomography (HRCT) scans obtained at baseline and after 2 years of therapy in patients treated with either cyclophosphamide (CYC) for 1 year or mycophenolate mofetil (MMF) for 2 years in Scleroderma Lung Study II. ILD patterns included lung fibrosis, ground glass, honeycombing, and normal lung. Net change was calculated as the difference in the probability of change from one ILD pattern to another. Wilcoxon's signed rank test was used to compare the changes.
February 2020Prediction of Idiopathic Pulmonary Fibrosis Progression Using Early Quantitative Changes on CT Imaging for a Short Term of Clinical 18-24-month Follow-ups.
Kim GHJ, Weigt SS, Belperio JA, Brown MS, Shi Y, Lai JH, Goldin JG.
OBJECTIVE: High-resolution computed tomography (HRCT) plays an indispensable role in the diagnosis of idiopathic pulmonary fibrosis (IPF). Due to unpredictability in progression and the short median survival of 2-5 years, it is critical to delineate the patients with rapid progression. The aim is to evaluate the predictability of IPF progression using the early quantitative changes. METHODS: Automated texture-based quantitative lung fibrosis (QLF) was calculated from the anonymized HRCT. Two datasets were collected retrospectively: (1) a pilot study of 35 subjects with three sequential scans (baseline and 6 and 12 months) to obtain a threshold, where visual assessments were stable at 6 months but worsened at 12 months; (2) 157 independent subjects to test the threshold. Landmark Cox regressions were used to compare the progression-free survival (PFS) defined by pulmonary function using the threshold from the early changes in QLF. C-indexes were reported as estimations of the concordance of prediction.
February 2020Key Components of Engineering Vascularized 3-dimensional Bioprinted Bone Constructs.
Shahabipour F, Ashammakhi N, Oskuee RK, Bonakdar S, Hoffman T, Shokrgozar MA, Khademhosseini A.
Vascularization has a pivotal role in engineering successful tissue constructs. However, it remains a major hurdle of bone tissue engineering, especially in clinical applications for the treatment of large bone defects. Development of vascularized and clinically-relevant engineered bone substitutes with sufficient blood supply capable of maintaining implant viability and supporting subsequent host tissue integration remains a major challenge. Since only cells that are 100-200 µm from blood vessels can receive oxygen through diffusion, engineered constructs that are thicker than 400 µm face a challenging oxygenation problem. Following implantation in vivo, spontaneous ingrowth of capillaries in thick engineered constructs is too slow. Thus, it is critical to provide optimal conditions to support vascularization in engineered bone constructs. To achieve this, an in-depth understanding of the mechanisms of angiogenesis and bone development is required. In addition, it is also important to mimic the physiological milieu of native bone to fabricate more successful vascularized bone constructs. Numerous applications of engineered vascularization with cell-and/or microfabrication-based approaches seek to meet these aims. Three-dimensional (3D) printing promises to create patient-specific bone constructs in the future. In this review, we discuss the major components of fabricating vascularized 3D bioprinted bone constructs, analyze their related challenges, and highlight promising future trends.
February 2020Safety of Intravenous Thrombolysis Among Patients Taking Direct Oral Anticoagulants: A Systematic Review and Meta-Analysis.
Shahjouei S, Tsivgoulis G, Goyal N, Sadighi A, Mowla A, Wang M, Seiffge DJ, Zand R.
BACKGROUND AND PURPOSE: There are scarce data regarding the safety of intravenous thrombolysis (IVT) in acute ischemic stroke among patients on direct oral anticoagulants (DOACs). METHODS: We performed a systematic review and meta-analysis of the current literature. Data regarding all adult patients pretreated with DOAC who received IVT for acute ischemic stroke were recorded. Meta-analysis was performed by comparing the rate of symptomatic intracerebral hemorrhage in these patients with (1) stroke patients without prior anticoagulation therapy and (2) patients on warfarin with international normalized ratio <1.7. Meta-analyses were further conducted in subgroups as follows: (1) administration of DOAC within 48 hours versus an unknown interval before IVT, (2) consideration of symptomatic intracerebral hemorrhage outcome according to the National Institute of Neurological Disorders (NINDS) versus the European Cooperative Acute Stroke Study II (ECASS-II) criteria.
February 2020Reduced Left Amygdala Volume in Patients with Dissociative Seizures (Psychogenic Nonepileptic Seizures).
Tatekawa H, Kerr WT, Savic I, Engel J Jr, Salamon N.
PURPOSE: This study specifically investigated differences of amygdalar and hippocampal volumes between patients with dissociative seizures (DS), mesial temporal lobe sclerosis (MTS), and normal controls (NC). METHODS: Between 2003 and 2018, 127 patients diagnosed with DS and 278 with MTS were recruited. An additional 52 NC subjects were recruited between 2015 and 2018. We retrospectively selected 29 patients with DS (male:female, 6:23) with absence of structural confounding factors and obtained sex- and age-matched MTS and NC. We used Neuroreader to assess the volume of the amygdala and hippocampus as a percentage of total intracranial volume based on thin-slice (0.9-1.2 mm) T1-weighted images. Statistical analyses controlled for psychiatric comorbidity and logistic regression were used to evaluate efficacy of these values for individual-level diagnosis.
February 2020Deep Learning Detection of Penumbral Tissue on Arterial Spin Labeling in Stroke.
Wang K, Shou Q, Ma SJ, Liebeskind D, Qiao XJ, Saver J, Salamon N, Kim H, Yu Y, Xie Y, Zaharchuk G, Scalzo F, Wang DJJ.
BACKGROUND and PURPOSE: Selection of patients with acute ischemic stroke for endovascular treatment generally relies on dynamic susceptibility contrast magnetic resonance imaging or computed tomography perfusion. Dynamic susceptibility contrast magnetic resonance imaging requires injection of contrast, whereas computed tomography perfusion requires high doses of ionizing radiation. The purpose of this work was to develop and evaluate a deep learning (DL)-based algorithm for assisting the selection of suitable patients with acute ischemic stroke for endovascular treatment based on 3-dimensional pseudo-continuous arterial spin labeling (pCASL). METHODS: A total of 167 image sets of 3-dimensional pCASL data from 137 patients with acute ischemic stroke scanned on 1.5T and 3.0T Siemens MR systems were included for neural network training. The concurrently acquired dynamic susceptibility contrast magnetic resonance imaging was used to produce labels of hypoperfused brain regions, analyzed using commercial software. The DL and 6 machine learning (ML) algorithms were trained with 10-fold cross-validation. The eligibility for endovascular treatment was determined retrospectively based on the criteria of perfusion/diffusion mismatch in the DEFUSE 3 trial (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke). The trained DL algorithm was further applied on twelve 3-dimensional pCASL data sets acquired on 1.5T and 3T General Electric MR systems, without fine-tuning of parameters.
January 2020Advances in Controlled Oxygen Generating Biomaterials for Tissue Engineering and Regenerative Therapy.
Ashammakhi N, Darabi MA, Kehr NS, Erdem A, Hu SK, Dokmeci MR, Nasr AS, Khademhosseini A.
Oxygen (O2) generating biomaterials are emerging as important compositions to improve our capabilities in supporting tissue engineering and regenerative therapeutics. Several in vitro studies demonstrated the usefulness of O2 releasing biomaterials in enhancing cell survival and differentiation. However, more efforts are needed to develop materials that can provide sustained O2 release for the long-term. In this paper, we present different O2 generating sources, including hydrogen peroxide, sodium percarbonate, calcium peroxide and magnesium peroxide, and also cover types of carriers and relevant methods of fabricating O2 generating systems. Then, the applications of O2 generating materials in supporting engineered constructs, supplying high O2 demanding cell transplants, and supporting ischemic tissues are discussed. Moreover, the challenges and future perspectives are highlighted.
January 2020Treatment of Recurrent Pulmonary Arteriovenous Malformations: Comparison of Proximal Versus Distal Embolization Technique.
Cusumano LR, Duckwiler GR, Roberts DG, McWilliams JP.
PURPOSE: To examine the characteristics of recurrent pulmonary arteriovenous malformations (PAVMs) and compare the success of proximal versus distal embolization technique for treatment of recanalized PAVMs. MATERIALS: Between July 2007 and October 2018, 26 consecutive patients underwent embolization of 64 previously treated recurrent PAVMs at a single center with imaging follow-up. PAVM angioarchitecture was classified as either simple (1 feeding artery) or complex (≥ 2 feeding arteries). The mechanism of recurrence was characterized as recanalization (flow through previously placed embolic material) or reperfusion (flow through accessory arteries). For recanalized PAVMs, we compared embolizing proximal to or within the existing embolic (proximal embolization technique) versus embolizing distal to the existing embolic (distal embolization technique). Follow-up imaging was reviewed to determine treatment success, defined as decrease of the draining vein or sac size by at least 70%.
January 2020Factors Associated with Symptomology of Celiac Artery Compression and Outcomes following Median Arcuate Ligament Release.
Khrucharoen U, Juo YY, Sanaiha Y, Finn JP, Jimenez JC, Dutson EP.
BACKGROUND: This study aims to identify potential risk factors for becoming symptomatic in patients with radiographic celiac artery compression (CAC) as well as prognostic factors for patients with median arcuate ligament syndrome (MALS) who underwent surgical ligament release. METHODS: This is a retrospective cohort study of patients with findings of CAC on computed tomography or magnetic resonance angiography (CT/MRA) who were asymptomatic and who were diagnosed with MALS at a single university hospital between January 2001 and 2018.
January 2020Cirrhotic Nodule Transformation to Hepatocellular Carcinoma: Natural History and Predictive Biomarkers on Contrast-Enhanced Ultrasound.
Lin M, Lu DS, Duan Y, Liao P, Sayre J, Xie X, Kuang M.
OBJECTIVE. The objective of our study was to identify sonographic biomarkers predicting or indicating eventual malignant transformation of pathologically confirmed cirrhotic nodules. MATERIALS AND METHODS. Thirty-nine consecutive patients with 44 pathologically confirmed cirrhotic nodules (mean size, 17.5 ± 8.5 [SD] mm) who initially underwent contrast-enhanced ultrasound examination at detection and then underwent follow-up conventional ultrasound every 3-4 months thereafter were retrospectively included. Malignant transformation was identified on the basis of noninvasive diagnostic criteria for hepatocellular carcinoma or rebiopsy. Malignant transformation biomarkers were identified from clinical and sonographic variables and the performance thereof was evaluated using ROC curves.
January 2020Long-Term Survival after Percutaneous Radiofrequency Ablation of Pathologically Proven Renal Cell Carcinoma in 100 Patients.
Marshall HR, Shakeri S, Hosseiny M, Sisk A, Sayre J, Lu DS, Pantuck A, Raman S.
PURPOSE: To determine the long-term survival of patients treated with percutaneous radiofrequency (RF) ablation for pathologically proven renal cell carcinoma (RCC). MATERIALS AND METHODS: In this single-center retrospective study, 100 patients with 125 RCCs (100 clear-cell, 19 papillary, and 6 chromophobe) 0.8-8 cm in size treated with RF ablation were evaluated at a single large tertiary-care center between 2004 and 2015. Technical success, primary and secondary technique efficacy, and pre- and postprocedural estimated glomerular filtration rate (eGFR) at 3-6 months and 2-3 years were recorded. Overall survival, cancer-specific survival, and local tumor progression-free survival were calculated by Kaplan-Meier survival curves. Complications were classified per the Clavien-Dindo system. Statistical testing was done via χ2 tests for proportions and paired t test for changes in eGFR. Statistical significance was set at α = 0.05.
January 2020Pamrevlumab, an Anti-connective Tissue Growth Factor Therapy, for Idiopathic Pulmonary Fibrosis (PRAISE): a Phase 2, Randomised, Double-blind, Placebo-controlled Trial.
Richeldi L, Fernández Pérez ER, Costabel U, Albera C, Lederer DJ, Flaherty KR, Ettinger N, Perez R, Scholand MB, Goldin J, Peony Yu KH, Neff T, Porter S, Zhong M, Gorina E, Kouchakji E, Raghu G.
BACKGROUND: Connective tissue growth factor (CTGF) is a secreted glycoprotein that has a central role in the process of fibrosis. This study was designed to assess the safety, tolerability, and efficacy of pamrevlumab (FG-3019), a fully recombinant human monoclonal antibody against CTGF, in idiopathic pulmonary fibrosis. The aim was to establish whether pamrevlumab could slow, stop, or reverse progression of idiopathic pulmonary fibrosis. METHODS: The phase 2, randomised, double-blind, placebo-controlled PRAISE trial was done at 39 medical centres in seven countries (Australia, Bulgaria, Canada, India, New Zealand, South Africa, and the USA). Patients with idiopathic pulmonary fibrosis and percentage of predicted forced vital capacity (FVC) of 55% or greater were enrolled and randomly assigned (1:1) by use of interactive responsive technology to intravenous infusion of pamrevlumab 30 mg/kg or placebo every 3 weeks over 48 weeks (16 infusions). The primary efficacy outcome was change from baseline in percentage of predicted FVC at week 48. Disease progression (defined as a decline from baseline in percentage of predicted FVC of ≥10%, or death) at week 48 was a key secondary efficacy outcome. All patients in the pamrevlumab group received at least one dose of the study drug and were analysed for safety. Two patients in the placebo group were excluded from the intention-to-treat population for the efficacy analyses because of enrolment error. This trial is registered with ClinicalTrials.gov, NCT01890265.
January 2020Patient Safety Analysis in Radiation Burden of Head Computed Tomography Imaging in 1185 Neurosurgical Inpatients.
Sheppard JP, Duong C, Romiyo P, Azzam D, Alkhalid Y, Nguyen T, Babayan D, Lagman C, Sun MZ, Prashant GN, Beckett JS, Yang I.
OBJECTIVE: We performed a retrospective analysis in a cohort of 1185 patients at our institution who were identified as undergoing ≥1 head computed tomography (CT) examinations during their inpatient stay on the neurosurgery service, to quantify the number, type, and associated radiation burden of head CT procedures performed by the neurosurgery service. METHODS: CT procedure records and radiology reports were obtained via database search and directly validated against records retrieved from manual chart review. Next, dosimetry data from the head CT procedures were extracted via automated text mining of electronic radiology reports.
January 2020Room-Temperature-Formed PEDOT:PSS Hydrogels Enable Injectable, Soft, and Healable Organic Bioelectronics.
Zhang S, Chen Y, Liu H, Wang Z, Ling H, Wang C, Ni J, Çelebi-Saltik B, Wang X, Meng X, Kim HJ, Baidya A, Ahadian S, Ashammakhi N, Dokmeci MR, Travas-Sejdic J, Khademhosseini A.
There is an increasing need to develop conducting hydrogels for bioelectronic applications. In particular, poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) hydrogels have become a research hotspot due to their excellent biocompatibility and stability. However, injectable PEDOT:PSS hydrogels have been rarely reported. Such syringe-injectable hydrogels are highly desirable for minimally invasive biomedical therapeutics. Here, an approach is demonstrated to develop injectable PEDOT:PSS hydrogels by taking advantage of the room-temperature gelation property of PEDOT:PSS. These PEDOT:PSS hydrogels form spontaneously after syringe injection of the PEDOT:PSS suspension into the desired location, without the need of any additional treatments. A facile strategy is also presented for large-scale production of injectable PEDOT:PSS hydrogel fibers at room temperature. Finally, it is demonstrated that these room-temperature-formed PEDOT:PSS hydrogels (RT-PEDOT:PSS hydrogel) and hydrogel fibers can be used for the development of soft and self-healable hydrogel bioelectronic devices.