February 2019Endovascular Transpulmonary Retrieval of a Migrated Amplatzer Vascular Plug Following Balloon-Occluded Retrograde Transvenous Obliteration.
Bundy JJ, Hussain J, Patel N, Khayat M, Chick JFB, Gemmete JJ, Srinivasa RN.
Gastric varices are a common manifestation of portal hypertension and are associated with a high rate of mortality and rebleeding. Balloon-occluded retrograde transvenous obliteration (BRTO) is a commonly used method to sclerose gastric varices and has a high clinical success. Common complications following BRTO include portal or splenic vein thrombosis, systemic sclerosant extravasation, pulmonary emboli, and inferior vena cava thrombosis. This report describes a patient with vascular plug migration into the left pulmonary artery with subsequent endovascular retrieval.
February 2019Patient Concerns and Perceptions Regarding Biologic Therapies in Ankylosing Spondylitis: Insights From a Large-Scale Survey of Social Media Platforms.
Dzubur E, Khalil C, Almario CV, Noah B, Minhas D, Ishimori M, Arnold C, Park Y, Kay J, Weisman MH, Spiegel BMR.
OBJECTIVE: Few studies have examined ankylosing spondylitis (AS) patients' concerns about and perceptions of biologic therapies, apart from traditional surveys. In this study, we used social media data to examine the knowledge, attitudes, and beliefs of AS patients regarding biologic therapies. METHODS: We collected posts published on 601 social media sites between January 1, 2016 and April 26, 2017. In each post, both an AS keyword and a biologic were mentioned. To explore themes within the collection of posts in an unsupervised manner, a latent Dirichlet allocation topic model was fit to the data set. Each discovered topic was represented as a discrete distribution over the words in the collection, similar to a word cloud. The topics were manually reviewed to identify themes, which were confirmed using thematic data analysis.
February 2019Pazopanib May Reduce Bleeding in Hereditary Hemorrhagic Telangiectasia.
Faughnan ME, Gossage JR, Chakinala MM, Oh SP, Kasthuri R, Hughes CCW, McWilliams JP, Parambil JG, Vozoris N, Donaldson J, Paul G, Berry P, Sprecher DL.
Pazopanib (Votrient) is an orally administered tyrosine kinase inhibitor that blocks VEGF receptors potentially serving as anti-angiogenic treatment for hereditary hemorrhagic telangiectasia (HHT). We report a prospective, multi-center, open-label, dose-escalating study [50 mg, 100 mg, 200 mg, and 400 mg], designed as a proof-of-concept study to demonstrate efficacy of pazopanib on HHT-related bleeding, and to measure safety. Patients, recruited at 5 HHT Centers, required ≥ 2 Curacao criteria AND [anemia OR severe epistaxis with iron deficiency]. Co-primary outcomes, hemoglobin (Hgb) and epistaxis severity, were measured during and after treatment, and compared to baseline. Safety monitoring occurred every 1.5 weeks. Seven patients were treated with 50 mg pazopanib daily. Six/seven showed at least 50% decrease in epistaxis duration relative to baseline at some point during study; 3 showed at least 50% decrease in duration during Weeks 11 and 12. Six patients showed a decrease in ESS of > 0.71 (MID) relative to baseline at some point during study; 3/6 showed a sustained improvement. Four patients showed > 2 gm improvement in Hgb relative to baseline at one or more points during study. Health-related QOL scores improved on all SF-36 domains at Week 6 and/or Week 12, except general health (unchanged). There were 19 adverse events (AE) including one severe AE (elevated LFTs, withdrawn from dosing at 43 days); with no serious AE. In conclusion, we observed an improvement in Hgb and/or epistaxis in all treated patients. This occurred at a dose much lower than typically used for oncologic indications, with no serious AE. Further studies of pazopanib efficacy are warranted.
February 2019Estimating a Size-specific Dose for Helical Head CT Examinations Using Monte Carlo Simulation Methods.
Hardy AJ, Bostani M, Hernandez AM, Zankl M, McCollough C, Cagnon C, Boone JM, McNitt-Gray M.
PURPOSE: Size-specific dose estimates (SSDE) conversion factors have been determined by AAPM Report 204 to adjust CTDIvol to account for patient size but were limited to body CT examinations. The purpose of this work was to determine conversion factors that could be used for an SSDE for helical, head CT examinations for patients of different sizes. METHODS: Validated Monte Carlo (MC) simulation methods were used to estimate dose to the center of the scan volume from a routine, helical head examination for a group of patient models representing a range of ages and sizes. Ten GSF/ICRP voxelized phantom models and five pediatric voxelized patient models created from CT image data were used in this study. CT scans were simulated using a Siemens multidetector row CT equivalent source model. Scan parameters were taken from the AAPM Routine Head protocols for a fixed tube current (FTC), helical protocol, and scan lengths were adapted to the anatomy of each patient model. MC simulations were performed using mesh tallies to produce voxelized dose distributions for the entire scan volume of each model. Three tally regions were investigated: (1) a small 0.6 cc volume at the center of the scan volume, (2) 0.8-1.0 cm axial slab at the center of the scan volume, and (3) the entire scan volume. Mean dose to brain parenchyma for all three regions was calculated. Mean bone dose and a mass-weighted average dose, consisting of brain parenchyma and bone, were also calculated for the slab in the central plane and the entire scan volume. All dose measures were then normalized by CTDIvol for the 16 cm phantom (CTDIvol,16 ). Conversion factors were determined by calculating the relationship between normalized doses and water equivalent diameter (Dw ).
February 2019Role of Clinical and Imaging Risk Factors in Predicting Breast Cancer Diagnosis Among BI-RADS 4 Cases.
Hsu W, Zhou X, Petruse A, Chau N, Lee-Felker S, Hoyt A, Wenger N, Elashoff D, Naeim A.
PURPOSE: To analyze women with suspicious findings (assessed as Breast Imaging Reporting and Data System [BI-RADS] 4), examining the value of clinical and imaging predictors in predicting cancer diagnosis. PATIENTS AND METHODS: A set of 2138 examinations (1978 women) given a BI-RADS 4 with matching pathology results were analyzed. Predictors such as patient demographics, clinical risk factors, and imaging-derived features such as BI-RADS assessment and qualitative breast density were considered. Independent predictors of breast cancer were determined by univariate analysis and multivariate logistic regression.
February 2019Selective Middle Cerebral Artery Occlusion in the Rabbit: Technique and Characterization with Pathologic Findings and Multimodal MRI.
Jahan R, Villablanca JP, Harris RJ, Duarte-Vogel S, Williams CK, Vinters HV, Rao N, Enzmann DR, Ellingson BM.
BACKGROUND: A reliable animal model of ischemic stroke is vital for pre-clinical evaluation of stroke therapies. We describe a reproducible middle cerebral artery (MCA) embolic occlusion in the French Lop rabbit characterized with multimodal MRI and histopathologic tissue analysis. NEW METHOD: Fluoroscopic-guided microcatheter placement was performed in five consecutive subjects with angiographic confirmation of MCA occlusion with autologous clot. Multimodal MRI was obtained prior to occlusion and up to six hours post after which repeat angiography confirmed sustained occlusion. The brain was harvested for histopathologic examination.
February 2019Cardiac Fibrotic Remodeling on a Chip with Dynamic Mechanical Stimulation.
Kong M, Lee J, Yazdi IK, Miri AK, Lin YD, Seo J, Zhang YS, Khademhosseini A, Shin SR.
Cardiac tissue is characterized by being dynamic and contractile, imparting the important role of biomechanical cues in the regulation of normal physiological activity or pathological remodeling. However, the dynamic mechanical tension ability also varies due to extracellular matrix remodeling in fibrosis, accompanied with the phenotypic transition from cardiac fibroblasts (CFs) to myofibroblasts. It is hypothesized that the dynamic mechanical tension ability regulates cardiac phenotypic transition within fibrosis in a strain-mediated manner. In this study, a microdevice that is able to simultaneously and accurately mimic the biomechanical properties of the cardiac physiological and pathological microenvironment is developed. The microdevice can apply cyclic compressions with gradient magnitudes (5-20%) and tunable frequency onto gelatin methacryloyl (GelMA) hydrogels laden with CFs, and also enables the integration of cytokines. The strain-response correlations between mechanical compression and CFs spreading, and proliferation and fibrotic phenotype remolding, are investigated. Results reveal that mechanical compression plays a crucial role in the CFs phenotypic transition, depending on the strain of mechanical load and myofibroblast maturity of CFs encapsulated in GelMA hydrogels. The results provide evidence regarding the strain-response correlation of mechanical stimulation in CFs phenotypic remodeling, which can be used to develop new preventive or therapeutic strategies for cardiac fibrosis.
February 2019Biodegradable Gelatin Methacryloyl Microneedles for Transdermal Drug Delivery.
Luo Z, Sun W, Fang J, Lee K, Li S, Gu Z, Dokmeci MR, Khademhosseini A.
Biocompatible and bioresponsive microneedles (MNs) are emerging technology platforms for sustained drug release with a potential to be a key player in transdermal delivery of therapeutics. In this paper, an innovative biodegradable MNs patch for the sustained delivery of drugs using a polymer patch, which can adjust delivery rates based on its crosslinking degree, is reported. Gelatin methacryloyl (GelMA) is used as the base for engineering biodegradable MNs. The anticancer drug doxorubicin (DOX) is loaded into GelMA MNs using the one molding step. The GelMA MNs can efficiently penetrate the stratum corneum layer of a mouse cadaver skin. Mechanical properties and drug release behavior of the GelMA MNs can be adjusted by tuning the degree of crosslinking. The efficacy of the DOX released from the GelMA MNs is tested and the anticancer efficacy of the released drugs against melanoma cell line A375 is demonstrated. Since GelMA is a versatile material in engineering tissue scaffolds, it is expected that the GelMA MNs can be used as a platform for the delivery of various therapeutics.
February 2019Knot in the Right Place.
Moriarty JM, Gonzalez Quesada CJ, Wang AC, Yang EH.
A 49-year-old female with pleuritic chest discomfort and dyspnea on exertion was found to have an unexpected intracardiac foreign object. A ventriculoperitoneal shunt (VPS) had been placed 5 years earlier. Chest radiography immediately after placement was unremarkable. Once migrated into the venous system and pulmonary artery, it had formed a tight knot with adherent thrombus, as noted after retrieval (Fig 3). Transfemoral endovascular removal was performed using a snare advanced through a 70-cm-long 14-Fr sheath. After its withdrawal, the pleuritic pain continued. A new VPS was inserted. VPSs have been known to kink and migrate into the pulmonary arteries. The most likely mechanism for entry into the venous system is unrecognized traversal of a neck vein during VPS placement. The soft catheter can be later "sucked" into the venous system with respiration.
February 2019Recanalization of Prostatic Artery Chronic Total Occlusion Prior to Prostatic Artery Embolization.
Plotnik AN, Roberts DG, Srinivasa RN, McWilliams JP.
Urinary obstruction secondary to benign prostatic hyperplasia is a late manifestation of the disease, and a poor prognostic sign for responding to conservative therapies. Prostatic artery embolization - when performed successfully - can be an effective treatment for reducing obstructive urinary symptoms. Outlined in this report is the successful recanalization of a prostatic artery chronic total occlusion prior to embolization in an 89-year-old man with benign prostatic hyperplasia, who initially presented with urinary obstruction. Prostatic artery recanalization was possible using a specialized crossing technique from peripheral arterial disease interventions, and allowed for more distal embolization of the prostate gland. This technique may be useful when advanced atherosclerotic disease limits the feasibility and clinical success of prostatic artery embolization.
February 2019Noninvasive Assessment of Hepatocellular Carcinoma Tumor Thrombus: Is It All in Vein?
Quirk MT, Lu DS.
The detection of portal vein tumor thrombus (PVTT) in patients with hepatocellular carcinoma (HCC) has important implications for prognosis and treatment. Liver transplantation (LT) is contraindicated due to high rates of recurrence, and the presence of PVTT also informs the choice of locoregional therapy. PVTT and other forms of macrovascular invasion figure into most of the major staging systems for HCC.
February 2019Remote Training and Oversight of Sonography for Human Immunodeficiency Virus-Associated Tuberculosis in Malawi.
Schwab K, Hoffman RM, Phiri L, Kahn D, Longwe L, Banda BA, Gama K, Chimombo M, Shih R, Schooley A, Pool KL.
The diagnosis of tuberculosis (TB) in patients infected with human immunodeficiency virus (HIV) can be challenging in resource-limited settings. Extrapulmonary TB is particularly underdiagnosed, with data suggesting that half of patients with disseminated TB are not diagnosed until autopsy.
February 2019A Foreign Body Response-on-a-Chip Platform.
Sharifi F, Htwe SS, Righi M, Liu H, Pietralunga A, Yesil-Celiktas O, Maharjan S, Cha BH, Shin SR, Dokmeci MR, Vrana NE, Ghaemmaghami AM, Khademhosseini A, Zhang YS.
Understanding the foreign body response (FBR) and desiging strategies to modulate such a response represent a grand challenge for implant devices and biomaterials. Here, the development of a microfluidic platform is reported, i.e., the FBR-on-a-chip (FBROC) for modeling the cascade of events during immune cell response to implants. The platform models the native implant microenvironment where the implants are interfaced directly with surrounding tissues, as well as vasculature with circulating immune cells. The study demonstrates that the release of cytokines such as monocyte chemoattractant protein 1 (MCP-1) from the extracellular matrix (ECM)-like hydrogels in the bottom tissue chamber induces trans-endothelial migration of circulating monocytes in the vascular channel toward the hydrogels, thus mimicking implant-induced inflammation. Data using patient-derived peripheral blood mononuclear cells further reveal inter-patient differences in FBR, highlighting the potential of this platform for monitoring FBR in a personalized manner. The prototype FBROC platform provides an enabling strategy to interrogate FBR on various implants, including biomaterials and engineered tissue constructs, in a physiologically relevant and individual-specific manner.
February 2019Microfluidic-enabled Bottom-up Hydrogels from Annealable Naturally-derived Protein Microbeads.
Sheikhi A, de Rutte J, Haghniaz R, Akouissi O, Sohrabi A, Di Carlo D, Khademhosseini A.
Naturally-derived proteins, such as collagen, elastin, fibroin, and gelatin (denatured collagen) hold a remarkable promise for tissue engineering and regenerative medicine. Gelatin methacryloyl (GelMA), synthesized from the methacryloyl modification of gelatin, mimicking the structure of extracellular matrix, has widely been used as a universal multi-responsive scaffold for a broad spectrum of applications, spanning from cell therapy to bioprinting and organoid development. Despite the widespread applications of GelMA, coupled stiffness and porosity has inhibited its applications in 3D cellular engineering wherein a stiff scaffold with large pores is demanded (e.g., at concentrations >10 wt%). Taking advantage of the orthogonal thermo-chemical responsivity of GelMA, we have developed microfluidic-assisted annealable GelMA beads, that are first stabilized by temperature-mediated physical crosslinking, flowed to form a scaffold structure, and then chemically annealed using light to fabricate novel bead-based 3D GelMA scaffolds with high mechanical resilience. We show how beaded GelMA (B-GelMA) provides a self-standing microporous environment with an orthogonal void fraction and stiffness, promoting cell adhesion, proliferation, and rapid 3D seeding at a high polymer concentration (~20 wt%) that would otherwise be impossible for bulk GelMA. B-GelMA, decorated with methacryloyl and arginylglycylaspartic acid (RGD) peptide motifs, does not require additional functionalization for annealing and cell adhesion, providing a versatile biorthogonal platform with orthogonal stiffness and porosity for a myriad of biomedical applications. This technology provides a universal method to convert polymeric materials with orthogonal physico-chemical responsivity to modular platforms, opening a new horizon for converting bulk hydrogels to beaded hydrogels (B-hydrogels) with decoupled porosity and stiffness.
January 20193D R✱2 Mapping of the Placenta During Early Gestation Using Free-breathing Multiecho Stack-of-radial MRI at 3T.
Armstrong T, Liu D, Martin T, Masamed R, Janzen C, Wong C, Chanlaw T, Devaskar SU, Sung K, Wu HH.
BACKGROUND: Multiecho gradient-echo Cartesian MRI characterizes placental oxygenation by quantifying R✱2. Previous research was performed at 1.5T using breath-held 2D imaging during later gestational age (GA). PURPOSE: To evaluate the accuracy and repeatability of a free-breathing (FB) 3D multiecho gradient-echo stack-of-radial technique (radial) for placental R✱2 mapping at 3T and report placental R✱2 during early GA. STUDY TYPE: Prospective. POPULATION: Thirty subjects with normal pregnancies and three subjects with ischemic placental disease (IPD) were scanned twice: between 14-18 and 19-23 weeks GA. FIELD STRENGTH: 3T. SEQUENCE: FB radial. ASSESSMENT: Linear correlation (concordance coefficient, ρc ) and Bland-Altman analyses (mean difference, MD) were performed to evaluate radial R✱2 mapping accuracy compared to Cartesian in a phantom. Radial R✱2 mapping repeatability was characterized using the coefficient of repeatability (CR) between back-to-back scans. The mean and spatial coefficient of variation (CV) of R✱2 was determined for all subjects, and separately for anterior and posterior placentas, at each GA range. STATISTICAL TESTS: ρc was tested for significance. Differences in mean R✱2 and CV were tested using Wilcoxon Signed-Rank and Rank-Sum tests. P < 0.05 was considered significant. Z-scores for the IPD subjects were determined.
January 2019Minimally Invasive and Regenerative Therapeutics.
Ashammakhi N, Ahadian S, Darabi MA, El Tahchi M, Lee J, Suthiwanich K, Sheikhi A, Dokmeci MR, Oklu R, Khademhosseini A.
Advances in biomaterial synthesis and fabrication, stem cell biology, bioimaging, microsurgery procedures, and microscale technologies have made minimally invasive therapeutics a viable tool in regenerative medicine. Therapeutics, herein defined as cells, biomaterials, biomolecules, and their combinations, can be delivered in a minimally invasive way to regenerate different tissues in the body, such as bone, cartilage, pancreas, cardiac, skeletal muscle, liver, skin, and neural tissues. Sophisticated methods of tracking, sensing, and stimulation of therapeutics in vivo using nano-biomaterials and soft bioelectronic devices provide great opportunities to further develop minimally invasive and regenerative therapeutics (MIRET). In general, minimally invasive delivery methods offer high yield with low risk of complications and reduced costs compared to conventional delivery methods. Here, minimally invasive approaches for delivering regenerative therapeutics into the body are reviewed. The use of MIRET to treat different tissues and organs is described. Although some clinical trials have been performed using MIRET, it is hoped that such therapeutics find wider applications to treat patients. Finally, some future perspective and challenges for this emerging field are highlighted.
January 2019Simulating Inflammation in a Wound Microenvironment Using a Dermal Wound-on-a-Chip Model.
Biglari S, Le TYL, Tan RP, Wise SG, Zambon A, Codolo G, De Bernard M, Warkiani M, Schindeler A, Naficy S, Valtchev P, Khademhosseini A, Dehghani F.Considerable progress has been made in the field of microfluidics to develop complex systems for modeling human skin and dermal wound healing processes. While microfluidic models have attempted to integrate multiple cell types and/or 3D culture systems, to date they have lacked some elements needed to fully represent dermal wound healing. This paper describes a cost-effective, multicellular microfluidic system that mimics the paracrine component of early inflammation close to normal wound healing. Collagen and Matrigel are tested as materials for coating and adhesion of dermal fibroblasts and human umbilical vein endothelial cells (HUVECs). The wound-on-chip model consists of three interconnecting channels and is able to simulate wound inflammation by adding tumor necrosis factor alpha (TNF-α) or by triculturing with macrophages. Both the approaches significantly increase IL-1β, IL-6, IL-8 in the supernatant (p < 0.05), and increases in cytokine levels are attenuated by cotreatment with an anti-inflammatory agent, Dexamethasone. Incorporation of M1 and M2 macrophages cocultured with fibroblasts and HUVECs leads to a stimulation of cytokine production as well as vascular structure formation, particularly with M2 macrophages. In summary, this wound-on-chip system can be used to model the paracrine component of the early inflammatory phase of wound healing and has the potential for the screening of anti-inflammatory compounds.
January 2019Association of Qualitative and Quantitative Imaging Features on Multiphasic Multidetector CT with Tumor Grade in Clear Cell Renal Cell Carcinoma.
Coy H, Young JR, Douek ML, Pantuck A, Brown MS, Sayre J, Raman SS.
PURPOSE: The purpose of the study was to determine if enhancement features and qualitative imaging features on multiphasic multidetector computed tomography (MDCT) were associated with tumor grade in patients with clear cell renal cell carcinoma (ccRCC). METHODS: In this retrospective, IRB approved, HIPAA-compliant, institutional review board-approved study with waiver of informed consent, 127 consecutive patients with 89 low grade (LG) and 43 high grade (HG) ccRCCs underwent preoperative four-phase MDCT in unenhanced (UN), corticomedullary (CM), nephrographic (NP), and excretory (EX) phases. Previously published quantitative (absolute peak lesion enhancement, absolute peak lesion enhancement relative to normal enhancing renal cortex, 3D whole lesion enhancement and the wash-in/wash-out of enhancement within the 3D whole lesion ROI) and qualitative (enhancement pattern; presence of necrosis; pattern of; tumor margin; tumor-parenchymal interface, tumor-parenchymal interaction; intratumoral vascularity; collecting system infiltration; renal vein invasion; and calcification) assessments were obtained for each lesion independently by two fellowship-trained genitourinary radiologists. Comparisons between variables included X2, ANOVA, and student t test. p values less than 0.05 were considered to be significant. Inter-reader agreement was obtained with the Gwet agreement coefficient (AC1) and standard error (SE) was reported.
January 20193D Cell-laden Polymers to Release Bioactive Products in the Eye.
Orive G, Santos-Vizcaino E, Pedraz JL, Hernandez RM, Vela Ramirez JE, Dolatshahi-Pirouz A, Khademhosseini A, Peppas NA, Emerich DF.Millions of people worldwide suffer from debilitating, progressive, and often permanent loss of vision without any viable treatment options. The complex physiological barriers of the eye contribute to the difficulty in developing novel therapies by limiting our ability to deliver therapeutics in a sustained and controlled manner; especially when attempting to deliver drugs to the posterior eye or trying to regenerate the diseased retina. Cell-based therapies offer a significant potential advancement in these situations. In particular, encapsulating, or immunoisolating, cells within implantable, semi-permeable membranes has emerged as a clinically viable means of delivering therapeutic molecules to the eye for indefinite periods of time. The optimization of encapsulation device designs is occurring together with refinements in biomaterials, genetic engineering, and stem-cell production, yielding, for the first time, the possibility of widespread therapeutic use of this technology. Here, we highlight the status of the most advanced and widely explored iteration of cell encapsulation with an eye toward translating the potential of this technological approach to the medical reality.
January 2019Calibration Strategies for Use of the NanoDot OSLD in CT Applications.
Scarboro SB, Cody D, Stingo FC, Alvarez P, Followill D, Court L, Zhang D, McNitt-Gray M, Kry SF.
Aluminum oxide based optically stimulated luminescent dosimeters (OSLD) have been recognized as a useful dosimeter for measuring CT dose, particularly for patient dose measurements. Despite the increasing use of this dosimeter, appropriate dosimeter calibration techniques have not been established in the literature; while the manufacturer offers a calibration procedure, it is known to have relatively large uncertainties. The purpose of this work was to evaluate two clinical approaches for calibrating these dosimeters for CT applications, and to determine the uncertainty associated with measurements using these techniques. Three unique calibration procedures were used to calculate dose for a range of CT conditions using a commercially available OSLD and reader. The three calibration procedures included calibration (a) using the vendor-provided method, (b) relative to a 120 kVp CT spectrum in air, and (c) relative to a megavoltage beam (implemented with 60 Co). The dose measured using each of these approaches was compared to dose measured using a calibrated farmer-type ion chamber. Finally, the uncertainty in the dose measured using each approach was determined. For the CT and megavoltage calibration methods, the dose measured using the OSLD nanoDot was within 5% of the dose measured using an ion chamber for a wide range of different CT scan parameters (80-140 kVp, and with measurements at a range of positions). When calibrated using the vendor-recommended protocol, the OSLD measured doses were on average 15.5% lower than ion chamber doses. Two clinical calibration techniques have been evaluated and are presented in this work as alternatives to the vendor-provided calibration approach. These techniques provide high precision for OSLD-based measurements in a CT environment.
January 2019Recent Advances in Nanoengineering Cellulose for Cargo Delivery.
Sheikhi A, Hayashi J, Eichenbaum J, Gutin M, Kuntjoro N, Khorsandi D, Khademhosseini A.
The recent decade has witnessed a growing demand to substitute synthetic materials with naturally-derived platforms for minimizing their undesirable footprints in biomedicine, environment, and ecosystems. Among the natural materials, cellulose, the most abundant biopolymer in the world with key properties, such as biocompatibility, biorenewability, and sustainability has drawn significant attention. The hierarchical structure of cellulose fibers, one of the main constituents of plant cell walls, has been nanoengineered and broken down to nanoscale building blocks, providing an infrastructure for nanomedicine. Microorganisms, such as certain types of bacteria, are another source of nanocelluloses known as bacterial nanocellulose (BNC), which benefit from high purity and crystallinity. Chemical and mechanical treatments of cellulose fibrils made up of alternating crystalline and amorphous regions have yielded cellulose nanocrystals (CNC), hairy CNC (HCNC), and cellulose nanofibrils (CNF) with dimensions spanning from a few nanometers up to several microns. Cellulose nanocrystals and nanofibrils may readily bind drugs, proteins, and nanoparticles through physical interactions or be chemically modified to covalently accommodate cargos. Engineering surface properties, such as chemical functionality, charge, area, crystallinity, and hydrophilicity, plays a pivotal role in controlling the cargo loading/releasing capacity and rate, stability, toxicity, immunogenicity, and biodegradation of nanocellulose-based delivery platforms. This review provides insights into the recent advances in nanoengineering cellulose crystals and fibrils to develop vehicles, encompassing colloidal nanoparticles, hydrogels, aerogels, films, coatings, capsules, and membranes, for the delivery of a broad range of bioactive cargos, such as chemotherapeutic drugs, anti-inflammatory agents, antibacterial compounds, and probiotics. SYNOPSIS: Engineering certain types of microorganisms as well as the hierarchical structure of cellulose fibers, one of the main building blocks of plant cell walls, has yielded unique families of cellulose-based nanomaterials, which have leveraged the effective delivery of bioactive molecules.
January 2019Engineering Precision Medicine.
Sun W, Lee J, Zhang S, Benyshek C, Dokmeci MR, Khademhosseini A.
Advances in genomic sequencing and bioinformatics have led to the prospect of precision medicine where therapeutics can be advised by the genetic background of individuals. For example, mapping cancer genomics has revealed numerous genes that affect the therapeutic outcome of a drug. Through materials and cell engineering, many opportunities exist for engineers to contribute to precision medicine, such as engineering biosensors for diagnosis and health status monitoring, developing smart formulations for the controlled release of drugs, programming immune cells for targeted cancer therapy, differentiating pluripotent stem cells into desired lineages, fabricating bioscaffolds that support cell growth, or constructing "organs-on-chips" that can screen the effects of drugs. Collective engineering efforts will help transform precision medicine into a more personalized and effective healthcare approach. As continuous progress is made in engineering techniques, more tools will be available to fully realize precision medicine's potential.
January 2019A System Using Patient-specific 3D-printed Molds to Spatially Align in vivo MRI with ex vivo MRI and Whole-mount Histopathology for Prostate Cancer Research.
Wu HH, Priester A, Khoshnoodi P, Zhang Z, Shakeri S, Afshari Mirak S, Asvadi NH, Ahuja P, Sung K, Natarajan S, Sisk A, Reiter R, Raman S, Enzmann D.
BACKGROUND: Patient-specific 3D-printed molds and ex vivo MRI of the resected prostate have been two important strategies to align MRI with whole-mount histopathology (WMHP) for prostate cancer (PCa) research, but the combination of these two strategies has not been systematically evaluated. PURPOSE: To develop and evaluate a system that combines patient-specific 3D-printed molds with ex vivo MRI (ExV) to spatially align in vivo MRI (InV), ExV, and WMHP in PCa patients. STUDY TYPE: Prospective cohort study. POPULATION: Seventeen PCa patients who underwent 3T MRI and robotic-assisted laparoscopic radical prostatectomy (RALP). FIELD STRENGTH/SEQUENCES: T2 -weighted turbo spin-echo sequences at 3T. ASSESSMENT: Immediately after RALP, the fresh whole prostate specimens were imaged in patient-specific 3D-printed molds by 3T MRI and then sectioned to create WMHP slides. The time required for ExV was measured to assess impact on workflow. InV, ExV, and WMHP images were registered. Spatial alignment was evaluated using: slide offset (mm) between ExV slice locations and WMHP slides; overlap of the 3D prostate contour on InV versus ExV using Dice's coefficient (0 to 1); and 2D target registration error (TRE, mm) between corresponding landmarks on InV, ExV, and WMHP. Data are reported as mean ± standard deviation (SD). STATISTICAL TESTING: Differences in 2D TRE before versus after registration were compared using the Wilcoxon signed-rank test (P < 0.05 considered significant).
January 2019Computed Tomographic Biomarkers in Idiopathic Pulmonary Fibrosis. The Future of Quantitative Analysis.
Wu X, Kim GH, Salisbury ML, Barber D, Bartholmai BJ, Brown KK, Conoscenti CS, De Backer J, Flaherty KR, Gruden JF, Hoffman EA, Humphries SM, Jacob J, Maher TM, Raghu G, Richeldi L, Ross BD, Schlenker-Herceg R, Sverzellati N, Wells AU, Martinez FJ, Lynch DA, Goldin J, Walsh SLF.
Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease with great variability in disease severity and rate of progression. The need for a reliable, sensitive, and objective biomarker to track disease progression and response to therapy remains a great challenge in IPF clinical trials. Over the past decade, quantitative computed tomography (QCT) has emerged as an area of intensive research to address this need. We have gathered a group of pulmonologists, radiologists and scientists with expertise in this area to define the current status and future promise of this imaging technique in the evaluation and management of IPF. In this Pulmonary Perspective, we review the development and validation of six computer-based QCT methods and offer insight into the optimal use of an imaging-based biomarker as a tool for prognostication, prediction of response to therapy, and potential surrogate endpoint in future therapeutic trials.
January 2019Ultra-low-dose CT Image Denoising Using Modified BM3D Scheme Tailored to Data Statistics.
Zhao T, Hoffman J, McNitt-Gray M, Ruan D.
PURPOSE: It is important to enhance image quality for low-dose CT acquisitions to push the ALARA boundary. Current state-of-the-art block-matching three-dimensional (BM3D) denoising scheme assumes white Gaussian noise (WGN) model. This study proposes a novel filtering module to be incorporated into the BM3D framework for ultra-low-dose CT denoising, by accounting for its specific power spectral properties. METHODS: In the current BM3D algorithm, the Wiener filtering is applied in the transform domain to a post-thresholding signal for enhanced denoising. However, unlike most natural/synthetic images, low-dose CTs do not obey the ideal Gaussian noise model. Based on the specific noise properties of ultra-low-dose CT, we derive the optimal transform-domain coefficients of Wiener filter based on the minimum mean-square-error (MMSE) criterion, taking the noise spectrum and the signal/noise cross spectrum into consideration. In the absence of ground-truth signal, the hard-thresholding denoising module in the previous stage is used as a plug-in estimator. We evaluate the denoising performance on thoracic CT image datasets containing paired full-dose and ultra-low-dose images simulated by a well-validated clinical engine (or pipeline). We also assess its clinical implication by applying the denoising methods to the emphysema quantification task. Our modified BM3D method is compared with the current one, using peak signal-to-noise ratio (PSNR) and emphysema scoring results as evaluation metrics.