The mission of the Department of Radiology at UMass Chan Medical School is to bring scientific advances in medical imaging to clinical application. This collection showcases journal articles and other publications written by faculty and researchers of the Department of Radiology.


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Recently Published

  • Cumulative effect of simvastatin, L-arginine, and tetrahydrobiopterin on cerebral blood flow and cognitive function in Alzheimer's disease

    Degrush, Elizabeth; Shazeeb, Mohammed Salman; Drachman, David; Vardar, Zeynep; Lindsay, Clifford; Gounis, Matthew J; Henninger, Nils (2022-09-17)
    Background and objectives: Vascular disease is a known risk factor for Alzheimer's disease (AD). Endothelial dysfunction has been linked to reduced cerebral blood flow. Endothelial nitric oxide synthase pathway (eNOS) upregulation is known to support endothelial health. This single-center, proof-of-concept study tested whether the use of three medications known to augment the eNOS pathway activity improves cognition and cerebral blood flow (CBF). Methods: Subjects with mild AD or mild cognitive impairment (MCI) were sequentially treated with the HMG-CoA reductase synthesis inhibitor simvastatin (weeks 0-16), L-arginine (weeks 4-16), and tetrahydrobiopterin (weeks 8-16). The primary outcome of interest was the change in CBF as measured by MRI from baseline to week 16. Secondary outcomes included standard assessments of cognition. Results: A total of 11 subjects were deemed eligible and enrolled. One subject withdrew from the study after enrollment, leaving 10 subjects for data analysis. There was a significant increase in CBF from baseline to week 8 by ~13% in the limbic and ~15% in the cerebral cortex. Secondary outcomes indicated a modest but significant increase in the MMSE from baseline (24.2±3.2) to week 16 (26.0±2.7). Exploratory analysis indicated that subjects with cognitive improvement (reduction of the ADAS-cog 13) had a significant increase in their respective limbic and cortical CBF. Conclusions: Treatment of mild AD/MCI subjects with medications shown to augment the eNOS pathway was well tolerated and associated with modestly increased cerebral blood flow and cognitive improvement. Trial registration: This study is registered in https://www. Clinicaltrials: gov ; registration identifier: NCT01439555; date of registration submitted to registry: 09/23/2011; date of first subject enrollment: 11/2011.
  • Characterization of optical clearing mechanisms in muscle during treatment with glycerol and gadobutrol solutions

    Silva, Hugo F; Martins, Inês S; Bogdanov, Alexei A. Jr.; Tuchin, Valery V; Oliveira, Luís M (2022-09-13)
    The recent increasing interest in the application of radiology contrasting agents to create transparency in biological tissues implies that the diffusion properties of those agents need evaluation. The comparison of those properties with the ones obtained for other optical clearing agents allows to perform an optimized agent selection to create optimized transparency in clinical applications. In this study, the evaluation and comparison of the diffusion properties of gadobutrol and glycerol in skeletal muscle was made, showing that although gadobutrol has a higher molar mass than glycerol, its low viscosity allows for a faster diffusion in the muscle. The characterization of the tissue dehydration and refractive index matching mechanisms of optical clearing was made in skeletal muscle, namely by the estimation of the diffusion coefficients for water, glycerol and gadobutrol. The estimated tortuosity values of glycerol (2.2) and of gadobutrol (1.7) showed a longer path-length for glycerol in the muscle.
  • The Woven EndoBridge (WEB) Device for the Treatment of Intracranial Aneurysms: Ten Years of Lessons Learned and Adjustments in Practice from the WorldWideWEB Consortium

    Dmytriw, Adam A; Dibas, Mahmoud; Ghozy, Sherief; Adeeb, Nimer; Diestro, Jose Danilo Bengzon; Phan, Kevin; Cuellar-Saenz, Hugo H; Sweid, Ahmad; Lay, Sovann V; Guenego, Adrien; et al. (2022-09-06)
    Several studies have shown promising outcomes of the Woven EndoBridge (WEB) device for the treatment of wide-necked intracranial bifurcation aneurysms. This is a multicenter study attempts to explore the changes in trends and treatment outcomes over time for WEB embolization of intracranial aneurysms. The WorldWideWEB consortium is a retrospective multicenter collaboration of data from international centers spanning from January 2011 and June 2021, with no limitations on aneurysm location or rupture status. Both bifurcation and sidewall aneurysms were included. These patients were stratified based on treatment year into five treatment intervals: 2011-2015 (N = 66), 2016-2017 (N = 77), 2018 (N = 66), 2019 (N = 300), and 2020-2021 (N = 173). Patient characteristics and angiographic and clinical outcomes were compared between these time intervals. This study comprised 671 patients (median age 61.4 years; 71.2% female) with 682 intracranial aneurysms. Over time, we observed an increasing tendency to treat patients presenting with ruptured aneurysms and aneurysms with smaller neck, diameter, and dome widths. Furthermore, we observed a trend towards more off-label use of the WEB for sidewall aneurysms and increased adoption of transradial access for WEB deployment. Moreover, the proportion of patients with adequate WEB occlusion immediately and at last follow-up was significantly higher in more recent year cohorts, as well as lower rates of compaction and retreatment. Mortality and complications did not differ over time. This learning curve study suggests improved experience using the WEB for the treatment of intracranial aneurysms and has yielded higher rates of adequate occlusion over time.
  • Guest Editorial for: "Addressing Disparities Related to Access of Multimodality Breast Imaging Services Before and During the COVID-19 Pandemic"

    DeBenedectis, Carolynn M (2022-09-06)
    The COVID-19 pandemic brought into the spotlight significant preexisting disparities in care throughout medicine, including Radiology; they most adversely affect racial minorities, patients of lower socioeconomic status, and those with no or inadequate health insurance. The article by Nguyen et al., entitled “Addressing Disparities Related to Access of Multimodality Breast Imaging Services Before and During the COVID-19 Pandemic” explores the disparities specific to access of breast imaging services due to the pandemic. Sixty percent of breast imaging services were delayed for all populations during the first 6 months of the pandemic, and it is projected that this will have a small negative impact on breast cancer mortality by 2030. This data is for overall populations but given some racial and ethnic minority populations (Blacks, Hispanics, and Native Americans) already have increased mortality from breast cancer it can be assumed that this will only compound the difference. In addition, breast cancer is the leading cause of cancer death in Hispanic women, but they had one of the lowest rebound screening mammography rates after the pandemic which is very concerning. This article is extremely important and should be used as a call to action for breast imaging departments to focus on addressing these now exacerbated disparities in these select populations.
  • Ligand-Specific Nano-Contrast Agents Promote Enhanced Breast Cancer CT Detection at 0.5 mg Au

    Ramesh, Kalyan; Truong, Alice; Wang, Yuzhen; Rusckowski, Mary; Gkikas, Manos (2022-09-01)
    For many cancer types, being undetectable from early symptoms or blood tests, or often detected at late stages, medical imaging emerges as the most efficient tool for cancer screening. MRI, ultrasound, X-rays (mammography), and X-ray CT (CT) are currently used in hospitals with variable costs. Diagnostic materials that can detect breast tumors through molecular recognition and amplify the signal at the targeting site in combination with state-of-the-art CT techniques, such as dual-energy CT, could lead to a more precise detection and assist significantly in image-guided intervention. Herein, we have developed a ligand-specific X-ray contrast agent that recognizes α5β1 integrins overexpressed in MDA-MB-231 breast cancer cells for detection of triple (-) cancer, which proliferates very aggressively. In vitro studies show binding and internalization of our nanoprobes within those cells, towards uncoated nanoparticles (NPs) and saline. In vivo studies show high retention of ~3 nm ligand-PEG-S-AuNPs in breast tumors in mice (up to 21 days) and pronounced CT detection, with statistical significance from saline and iohexol, though only 0.5 mg of metal were utilized. In addition, accumulation of ligand-specific NPs is shown in tumors with minimal presence in other organs, relative to controls. The prolonged, low-metal, NP-enhanced spectral-CT detection of triple (-) breast cancer could lead to breakthrough advances in X-ray cancer diagnostics, nanotechnology, and medicine.
  • COManeci MechANical dilation for vasospasm (COMMAND): multicenter experience

    Salem, Mohamed M; Khalife, Jane; Desai, Sohum; Sharashidze, Vera; Badger, Clint; Kuhn, Anna L; Monteiro, Andre; Salahuddin, Hisham; Siddiqui, Adnan H; Singh, Jasmeet; et al. (2022-08-24)
    Background: We report the largest multicenter experience to date of utilizing the Comaneci device for endovascular treatment of refractory intracranial vasospasm. Methods: Consecutive patients undergoing Comaneci mechanical dilatation for vasospasm were extracted from prospectively maintained registries in 11 North American centers (2020-2022). Intra-arterial vasodilators (IAV) were allowed, with the Comaneci device utilized after absence of vessel dilation post-infusion. Pre- and post-vasospasm treatment scores were recorded for each segment, with primary radiological outcome of score improvement post-treatment. Primary clinical outcome was safety/device-related complications, with secondary endpoints of functional outcomes at last follow-up. Results: A total of 129 vessels in 40 patients (median age 52 years; 67.5% females) received mechanical dilation, 109 of which (84.5%) exhibited pre-treatment severe-to-critical vasospasm (ie, score 3/4). Aneurysmal subarachnoid hemorrhage was the most common etiology of vasospasm (85%), with 65% of procedures utilizing Comaneci-17 (92.5% of patients received IAV). The most treated segments were anterior cerebral artery (34.9%) and middle cerebral artery (31%). Significant vasospasm drop (pre-treatment score (3-4) to post-treatment (0-2)) was achieved in 89.9% of vessels (96.1% of vessels experienced ≥1-point drop in score post-treatment). There were no major procedural/post-procedural device-related complications. Primary failure (ie, vessel unresponsive) was encountered in one vessel (1 patient) (1/129; 0.8%) while secondary failure (ie, recurrence in previously treated segment requiring retreatment in another procedure) occurred in 16 vessels (7 patients) (16/129; 12.4%), with median time-to-retreatment of 2 days. Favorable clinical outcome (modified Rankin Scale 0-2) was noted in 51.5% of patients (median follow-up 6 months). Conclusions: The Comaneci device provides a complementary strategy for treatment of refractory vasospasm with reasonable efficacy/favorable safety. Future prospective trials are warranted.
  • High-frequency optical coherence tomography predictors of aneurysm occlusion following flow diverter treatment in a preclinical model

    King, Robert M; Peker, Ahmet; Anagnostakou, Vania; Raskett, Christopher M; Arends, Jennifer M; Dixit, Harish G; Ughi, Giovanni J; Puri, Ajit S; Gounis, Matthew J; Shazeeb, Mohammed Salman (2022-08-24)
    Background: High-frequency optical coherence tomography (HF-OCT) is an intravascular imaging method that allows for volumetric imaging of flow diverters in vivo. Objective: To examine the hypothesis that a threshold for both volume and area of communicating malapposition can be predictive of early aneurysm occlusion. Methods: Fifty-two rabbits underwent elastase aneurysm formation, followed by treatment with a flow diverter. At the time of implant, HF-OCT was acquired to study the rate and degree of communicating malapposition. Treated aneurysms were allowed to heal for either 90 or 180 days and euthanized following catheter angiography. Healing was dichotomized into aneurysm remnant or neck remnant/complete occlusion. Communicating malapposition was measured by HF-OCT using a semi-automatic algorithm able to detect any points where the flow diverter was more than 50 µm from the vessel wall. This was then summed across image slices to either a volume or area. Finally, a subsampled population was used to train a statistical classifier for the larger dataset. Results: No difference in occlusion rate was found between device type or follow-up time (p=0.28 and p=0.67, respectively). Both volume and area of malapposition were significantly lower in aneurysms with a good outcome (p<0.001, both). From the statistical model, a volume of less than 0.56 mm3 or a normalized area less than 0.69 as quantified by HF-OCT was predictive of occlusion (p<0.001, each). Conclusions: HF-OCT allows for measurements of both volume and area of malapposition and, from these measurements, an accurate prediction for early aneurysm occlusion can be made.
  • What's new in cancer and molecular imaging

    McIntosh, Lacey J (2022-08-24)
  • Early-stage COVID-19 pandemic observations on pulmonary embolism using nationwide multi-institutional data harvesting

    Wismüller, Axel; DSouza, Adora M; Abidin, Anas Z; Ali Vosoughi, M; Gange, Christopher; Cortopassi, Isabel O; Bozovic, Gracijela; Bankier, Alexander A; Batra, Kiran; Chodakiewitz, Yosef; et al. (2022-08-19)
    We introduce a multi-institutional data harvesting (MIDH) method for longitudinal observation of medical imaging utilization and reporting. By tracking both large-scale utilization and clinical imaging results data, the MIDH approach is targeted at measuring surrogates for important disease-related observational quantities over time. To quantitatively investigate its clinical applicability, we performed a retrospective multi-institutional study encompassing 13 healthcare systems throughout the United States before and after the 2020 COVID-19 pandemic. Using repurposed software infrastructure of a commercial AI-based image analysis service, we harvested data on medical imaging service requests and radiology reports for 40,037 computed tomography pulmonary angiograms (CTPA) to evaluate for pulmonary embolism (PE). Specifically, we compared two 70-day observational periods, namely (i) a pre-pandemic control period from 11/25/2019 through 2/2/2020, and (ii) a period during the early COVID-19 pandemic from 3/8/2020 through 5/16/2020. Natural language processing (NLP) on final radiology reports served as the ground truth for identifying positive PE cases, where we found an NLP accuracy of 98% for classifying radiology reports as positive or negative for PE based on a manual review of 2,400 radiology reports. Fewer CTPA exams were performed during the early COVID-19 pandemic than during the pre-pandemic period (9806 vs. 12,106). However, the PE positivity rate was significantly higher (11.6 vs. 9.9%, p < 10-4) with an excess of 92 PE cases during the early COVID-19 outbreak, i.e., ~1.3 daily PE cases more than statistically expected. Our results suggest that MIDH can contribute value as an exploratory tool, aiming at a better understanding of pandemic-related effects on healthcare.
  • Exploring Factors Associated With Mobile Phone Behaviors and Attitudes Toward Technology Among Adults With Alcohol Use Disorder and Implications for mHealth Interventions: Exploratory Study

    Sillice, Marie Aline; Stein, Michael; Battle, Cynthia L; Meshesha, Lidia Z; Lindsay, Clifford; Agu, Emmanuel; Abrantes, Ana M (2022-08-15)
    Background: Alcohol use disorder (AUD) is associated with severe chronic medical conditions and premature mortality. Expanding the reach or access to effective evidence-based treatments to help persons with AUD is a public health objective. Mobile phone or smartphone technology has the potential to increase the dissemination of clinical and behavioral interventions (mobile health interventions) that increase the initiation and maintenance of sobriety among individuals with AUD. Studies about how this group uses their mobile phone and their attitudes toward technology may have meaningful implications for participant engagement with these interventions. Objective: This exploratory study examined the potential relationships among demographic characteristics (race, gender, age, marital status, and income), substance use characteristics (frequency of alcohol and cannabis use), and clinical variables (anxiety and depression symptoms) with indicators of mobile phone use behaviors and attitudes toward technology. Methods: A sample of 71 adults with AUD (mean age 42.9, SD 10.9 years) engaged in an alcohol partial hospitalization program completed 4 subscales from the Media Technology Usage and Attitudes assessment: Smartphone Usage measures various mobile phone behaviors and activities, Positive Attitudes and Negative Attitudes measure attitudes toward technology, and the Technological Anxiety/Dependence measure assesses level of anxiety when individuals are separated from their phone and dependence on this device. Participants also provided demographic information and completed the Epidemiologic Studies Depression Scale (CES-D) and the Generalized Anxiety Disorder (GAD-7) scale. Lastly, participants reported their frequency of alcohol use over the past 3 months using the Drug Use Frequency Scale. Results: Results for the demographic factors showed a significant main effect for age, Smartphone Usage (P=.003; ηp2=0.14), and Positive Attitudes (P=.01; ηp2=0.07). Marital status (P=.03; ηp2=0.13) and income (P=.03; ηp2=0.14) were associated only with the Technological Anxiety and Dependence subscale. Moreover, a significant trend was found for alcohol use and the Technological Anxiety/Dependence subscale (P=.06; R2=0.02). Lastly, CES-D scores (P=.03; R2=0.08) and GAD symptoms (P=.004; R2=0.13) were significant predictors only of the Technological Anxiety/Dependence subscale. Conclusions: Findings indicate differences in mobile phone use patterns and attitudes toward technology across demographic, substance use, and clinical measures among patients with AUD. These results may help inform the development of future mHealth interventions among this population.
  • Radiologists staunchly support patient safety and autonomy, in opposition to the SCOTUS decision to overturn Roe v Wade

    Karandikar, Aditya; Solberg, Agnieszka; Fung, Alice; Lee, Amie Y; Farooq, Amina; Taylor, Amy C; Oliveira, Amy; Narayan, Anand; Senter, Andi; Majid, Aneesa; et al. (2022-08-12)
  • Dawn of a New Era: Super Large-Bore Aspiration Catheters for Complete Clot Ingestion During Thrombectomy for Large-Vessel Occlusions

    Kuhn, Anna Luisa; Singh, Jasmeet; Anagnostakou, Vania; Massari, Francesco; Gounis, Matthew J; Puri, Ajit S (2022-08-11)
    The design and development of super large-bore aspiration catheters (SLACs) represent an important technologic advancement and possibly the biggest breakthrough in acute ischemic stroke (AIS) treatment since stent retrievers were introduced to the neurointerventional armamentarium more than 10 years ago. Catheters with inner diameters of 0.088 inch are routinely used as guide catheters, but the thought of advancing such large-lumen catheters into an M1 segment for mechanical thrombectomy was considered unsafe, if not outright impossible—until recently.
  • Imaging features of toxicities associated with immune checkpoint inhibitors

    Gosangi, Babina; McIntosh, Lacey; Keraliya, Abhishek; Irugu, David Victor Kumar; Baheti, Akshay; Khandelwal, Ashish; Thomas, Richard; Braschi-Amirfarzan, Marta (2022-08-08)
    The past decade has witnessed a change in landscape of cancer management with the advent of precision oncology. Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment and have played an important role in improving patient survival. While the patients are living longer, treatment with ICIs are sometimes associated with adverse effects, some of which could be fatal. Radiologists can play a crucial role by early identification of some of these adverse effects during restaging scans. Our paper focuses on the imaging features of commonly occurring ICI toxicities based on organ system.
  • Importance of tumor subtypes in cancer imaging

    Khader, Ali; Braschi-Amirfarzan, Marta; McIntosh, Lacey J; Gosangi, Babina; Wortman, Jeremy R; Wald, Christoph; Thomas, Richard (2022-07-26)
    Cancer therapy has evolved from being broadly directed towards tumor types, to highly specific treatment protocols that target individual molecular subtypes of tumors. With the ever-increasing data on imaging characteristics of tumor subtypes and advancements in imaging techniques, it is now often possible for radiologists to differentiate tumor subtypes on imaging. Armed with this knowledge, radiologists may be able to provide specific information that can obviate the need for invasive methods to identify tumor subtypes. Different tumor subtypes also differ in their patterns of metastatic spread. Awareness of these differences can direct radiologists to relevant anatomical sites to screen for early metastases that may otherwise be difficult to detect during cursory inspection. Likewise, this knowledge will help radiologists to interpret indeterminate findings in a more specific manner.
  • Intrasaccular flow disruption for ruptured aneurysms: an international multicenter study

    Diestro, Jose Danilo Bengzon; Dibas, Mahmoud; Adeeb, Nimer; Regenhardt, Robert W; Vranic, Justin E; Guenego, Adrien; Lay, Sovann V; Renieri, Leonardo; Al Balushi, Ali; Shotar, Eimad; et al. (2022-07-22)
    Background: The Woven EndoBridge (WEB) device is a novel intrasaccular flow disruptor tailored for bifurcation aneurysms. We aim to describe the degree of aneurysm occlusion at the latest follow-up, and the rate of complications of aneurysms treated with the WEB device stratified according to rupture status. Methods: Our data were taken from the WorldWideWeb Consortium, an international multicenter cohort including patients treated with the WEB device. Aneurysms were classified into two groups: ruptured and unruptured. We compared clinical and radiologic outcomes of both groups. Propensity score matching (PSM) was done to match according to age, gender, bifurcation, location, prior treatment, neck, height, dome width, daughter sac, incorporated branch, pretreatment antiplatelets, and last imaging follow-up. Results: The study included 676 patients with 691 intracranial aneurysms (529 unruptured and 162 ruptured) treated with the WEB device. The PSM analysis had 55 pairs. In both the unmatched (85.8% vs 84.3%, p=0.692) and matched (94.4% vs 83.3%, p=0.066) cohorts there was no significant difference in the adequate occlusion rate at the last follow-up. Likewise, there were no significant differences in both ischemic and hemorrhagic complications between the two groups. There was no documented aneurysm rebleeding after WEB device implantation. Conclusion: There was no significant difference in both the radiologic outcomes and complications between unruptured and ruptured aneurysms. Our findings support the feasibility of treatment of ruptured aneurysms with the WEB device.
  • Transradial access for cerebral angiography and neurointerventional procedures: A meta-analysis and systematic review

    Rentiya, Zubir S; Kuhn, Anna Luisa; Hutnik, Robert; Shazeeb, Mohammed Salman; De Leacy, Reade A; Goldman, Daryl; Singh, Jasmeet; Puri, Ajit S (2022-07-15)
    Purpose: Transradial access (TRA) for diagnostic and interventional neurointerventional procedures has recently gained traction over transfemoral access (TFA) in the neurointerventional community. This meta-analysis aims to assess and summarize the utility of TRA in cerebral angiography and neurointerventional procedures. Methods: A systematic literature review was performed utilizing Pubmed, Embase, and Scopus databases. Using PRISMA guidelines, records were extracted with the following search terms: transradial approach, transradial access, radial access, cerebral angiogram, cerebral angiography, neurointervention, and neuroendovascular. The primary outcomes assessed were case success rate, complication rate, and crossover rate from TRA to TFA. Secondary analysis was performed on procedure time, fluoroscopy time, fluoroscopy time per vessel (diagnostic procedures only), contrast dose, radial artery diameter, distal radial artery diameter, and patient preference for TRA over TFA. Results: Sixty-two full-text articles were analyzed for this meta-analysis, representing 12,927 diagnostic and interventional TRA access patients. Our analysis revealed a combined diagnostic and interventional case success rate of 95.9% and complication rate of 3.5%, with crossover to TFA occurring in 4.9% of cases. Conclusion: This meta-analysis demonstrates that TRA access for diagnostic angiography and neurointerventional procedures is a safe and effective approach, though determining a true complication rate is challenging as the definition of TRA complications has changed in various publications over time.
  • International Controlled Study of Revascularization and Outcomes Following COVID-Positive Mechanical Thrombectomy

    Dmytriw, Adam A.; Kuhn, Anna L.; Puri, Ajit S.; Jabbour, Pascal (2022-07-12)
    BACKGROUND: Previous studies suggest that the mechanisms and outcomes in COVID-19-associated stroke differ from those with non-COVID-19 strokes, but there is limited comparative evidence focusing on these populations. Therefore, we aimed to determine if a significant association exists between COVID-19 status with revascularization and functional outcomes following thrombectomy for large vessel occlusion (LVO), after adjustment for potential confounding factors. METHODS: A cross-sectional, international multicenter retrospective study of consecutively admitted COVID-19 patients with concomitant acute LVO, compared to a control group without COVID-19. Data collected included age, gender, comorbidities, clinical characteristics, details of the involved vessels, procedural technique, and various outcomes. A multivariable adjusted analysis was conducted. RESULTS: In this cohort of 697 patients with acute LVO, 302 had COVID-19 while 395 patients did not. There was a significant difference (p < 0.001) in the mean age (in years) and gender of patients, with younger patients and more males in the COVID-19 group. In terms of favorable revascularization (mTICI 3), COVID-19 was associated with lower odds of complete revascularization [OR=0.33; 95% CI=0.23-0.48; p < 0.001], which persisted on multivariable modelling with adjustment for other predictors [aOR=0.30; 95% CI=0.12-0.77; p=0.012]. Moreover, endovascular complications, in-hospital mortality, and length of hospital stay were significantly higher among COVID-19 patients (p < 0.001). CONCLUSION: COVID-19 was an independent predictor of incomplete revascularization and poor functional outcome in patients with stroke due to LVO. Furthermore, COVID-19 patients with LVO were more often younger and suffered higher morbidity/mortality rates.
  • Middle meningeal artery: An effective pathway for achieving complete obliteration following transarterial Ethylene Vinyl Copolymer (Onyx) embolization of dural arteriovenous fistulas

    Akamatsu, Yosuke; Gomez-Paz, Santiago; Tonetti, Daniel A; Vergara-Garcia, David; Moholkar, Viraj M; Kuhn, Anna Luisa; Chida, Kohei; Singh, Jasmeet; Rodrigues, Katyucia De Macedo; Massari, Francesco; et al. (2022-07-07)
    Objective: Transarterial Onyx embolization is the mainstay of intracranial non-cavernous dural arteriovenous fistulas (dAVFs) treatment. Although the dural arterial supply varies depending on the location, the impact of arterial access on treatment outcomes has remained unclear. The aim of this study was to characterize factors as sociated with complete obliteration following transarterial Onyx embolization, with a special focus on arterial access routes and dAVF location. Methods: A retrospective analysis of the patients who underwent transarterial Onyx embolization for intracranial dAVFs at two academic institutions was performed. Patients with angiographic follow-up were considered eligible to investigate the impact of the arterial access on achieving complete obliteration. Results: Sixty-eight patients underwent transarterial Onyx embolization of intracranial dAVFs. Complete obliteration was achieved in 65% of all treated patients and in 75% of those with cortical venous reflux. Multivariable analysis identified middle meningeal artery (MMA) access to be a significant independent predictive factor for complete obliteration (OR, 2.32; 95% CI, 1.06-5.06; p=0.034). Subgroup analysis showed that supratentorial and lateral cerebellar convexity dAVFs (OR, 5.72, 95% CI, 1.89-17.33, p=0.002), and Borden type III classification at pre-treatment (OR, 3.13, 95% CI, 1.05- 9.35, p=0.041), were independent predictive factors for complete obliteration following embolization through the MMA. Conclusions: MMA access is an independent predictive factor for complete obliteration following transarterial Onyx embolization for intracranial non-cavernous dAVFs. It is particularly effective for supratentorial and lateral cerebellar convexity dAVFs and those that are Borden type III.
  • A Keratinocyte-Tethered Biologic Enables Location-Precise Treatment in Mouse Vitiligo

    Hsueh, Ying-Chao; Wang, Yuzhen; Riding, Rebecca L; Catalano, Donna E; Lu, Yu-Jung; Richmond, Jillian M; Siegel, Don L; Rusckowski, Mary; Stanley, John R; Harris, John E (2022-07-02)
    Despite the central role of IFN-γ in vitiligo pathogenesis, systemic IFN-γ neutralization is an impractical treatment option owing to strong immunosuppression. However, most patients with vitiligo present with <20% affected body surface area, which provides an opportunity for localized treatments that avoid systemic side effects. After identifying keratinocytes as key cells that amplify IFN-γ signaling during vitiligo, we hypothesized that tethering an IFN-γ‒neutralizing antibody to keratinocytes would limit anti‒IFN-γ effects on the treated skin for the localized treatment. To that end, we developed a bispecific antibody capable of blocking IFN-γ signaling while binding to desmoglein expressed by keratinocytes. We characterized the effect of the bispecific antibody in vitro, ex vivo, and in a mouse model of vitiligo. Single-photon emission computed tomography/computed tomography biodistribution and serum assays after local footpad injection revealed that the bispecific antibody had improved skin retention, faster elimination from the blood, and less systemic IFN-γ inhibition than the nontethered version. Furthermore, the bispecific antibody conferred localized protection almost exclusively to the treated footpad during vitiligo, which was not possible by local injection of the nontethered anti‒IFN-γ antibody. Thus, keratinocyte tethering proved effective while significantly diminishing the off-tissue effects of IFN-γ blockade, offering a safer treatment strategy for localized skin diseases, including vitiligo.
  • Impact of histological clot composition on preprocedure imaging and mechanical thrombectomy

    Johnson, Jeremiah N; Srivatsan, Aditya; Chueh, Juyu; Arslanian, Rose; Gounis, Matthew J; Puri, Ajit S; Srinivasan, Visish M; Chen, Stephen Russell; Burkhardt, Jan-Karl; Kan, Peter (2022-06-30)
    Introduction: We studied the relationship of acute ischemic stroke (AIS) large-vessel occlusion clot composition with vessel recanalization and preprocedure imaging. Subjects and methods: Individual clots from AIS patients who underwent mechanical thrombectomy (MT) between September 2016 and September 2018 were examined. Clot composition was analyzed histologically through a trichrome staining and image segmentation, and the area occupied by red blood cells (RBCs), fibrin, or mixed composition was quantified. Results: Forty-three patients (65.4 ± 12.7 years, 39% of females) who underwent 92 retrieval passes (mean 2.14, range 1-6) were included in this study. Fibrin (44%) occupied the greatest area, followed by mixed composition (34%) and RBCs (22%). A stent retriever was deployed in 81% of cases, 20 patients (47%) achieved first-pass efficacy (FPE) (thrombolysis in cerebral infarction [TICI] 2b-3 after first pass), 41 (95%) achieved successful revascularization (TICI 2b-3), and 21 (49%) had good outcome (modified Rankin Scale [mRS] ≤2) at 90 days. Hyperdense artery sign (HAS) on initial computed tomography was correlated with mixed clot composition (P = 0.01) and lack of fibrin content (P = 0.03). In the univariate analysis, FPE was associated with RBC clot area, atrial fibrillation, and occlusion location but not with fibrin clot area, mixed clot area, stroke etiology, thrombectomy technique, distal emboli, or 90-day mRS. In the multivariate analysis, FPE was significantly correlated with low RBC clot area (odd ratio = 0.96, confidence interval [0.92.99], P = 0.034) but not with atrial fibrillation or location. Conclusion: Our results suggest that HAS is correlated with mixed clot composition and lower fibrin content and that lower RBC clot composition is associated with FPE in patients undergoing MT.

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