• 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.
    • Super large-bore ingestion of clot (SLIC) leads to high first pass effect in thrombectomy for large vessel occlusion

      Massari, Francesco; Dabus, Guilherme; Cortez, Gustavo M.; Singh, Jasmeet; Kuhn, Anna L.; Naragum, Varun; Anagnostakou, Vania; Hanel, Ricardo A.; Gounis, Matthew J.; Puri, Ajit S. (2022-06-22)
      BACKGROUND: Super large-bore aspiration (SLBA) has shown high rates of complete clot ingestion. OBJECTIVE: To report the initial clinical feasibility, safety, and efficacy of this novel SLBA insert combination-super large-bore ingestion of clot (SLIC) technique for stroke. METHODS: We performed a retrospective review of three comprehensive stroke center databases. The SLIC technique entails a triaxial assembly of an 8 Fr 0.106'' Base Camp catheter, 0.088'' catheter extender (HiPoint), and an insert catheter (Tenzing 8) that completely consumes the inner diameter of the 0.088'' SLBA catheter. The HiPoint catheter is delivered over the Tenzing 8 to the face of the embolus, which is withdrawn, while aspirating through the Base Camp and HiPoint catheters as a single assembly. RESULTS: Thirty-three consecutive patients with large vessel occlusion were treated with SLIC. The median age was 70 years (30-91) and 17 were male (51.5%). The median presenting National Institutes of Health Stroke Scale score and Alberta Stroke Program Early CT score was 21 (1-34) and 8 (5-10), respectively. There was 100% success in delivering the 0.088'' catheter to the site of the occlusion. The successful revascularization rate (modified Thrombolysis in Cerebral Infarction (mTICI) score > /=2B) was 100% within a single pass in most cases (82%). Final mTICI > /=2C was achieved in 94.1% of occlusions, with 73.5% mTICI 3 recanalization. The rate of first pass effect in achieving excellent reperfusion (mTICI > /=2C) was 70.5%. There were no adverse events or postprocedural symptomatic hemorrhages. CONCLUSIONS: Our initial experience with the SLIC technique resulted in achieving a first pass effect (mTICI > /=2C) in 70.5%. Navigation of the SLBA catheter extender over the Tenzing insert was successful and safe in this early experience.
    • Interventional oncology update

      Newbury, Alex; Ferguson, Chantal M.; Valero, Daniel Alvarez; Kutcher-Diaz, Roberto; McIntosh, Lacey J.; Karamanian, Ara; Harman, Aaron (2022-06-20)
      Interventional Oncology (IO) is a subspecialty field of Interventional Radiology bridging between diagnostic radiology and the clinical oncology team, addressing the diagnosis and treatment of cancer. There have been many exciting advancements in the field of IO in recent years; far too many to cover in a single paper. To give each topic sufficient attention, we have limited the scope of this review article to four topics which we feel have the potential to drastically change how cancer is treated managed in the immediate future.
    • Clinical Diagnoses and Outcomes After Diagnostic Breast Ultrasound by Nurses and General Practitioner Physicians in Rural Rwanda

      Pace, Lydia E.; Dusengimana, Jean-Marie Vianney; Hategekimana, Vedaste; Rugema, Vestine; Umwizerwa, Aline; Frost, Elisabeth; Kwait, Dylan; Schleimer, Lauren E.; Huang, ChuanChin; Shyirambere, Cyprien; et al. (2022-06-20)
      PURPOSE: To scale up early detection of breast cancer in low- and middle-income countries, research is needed to inform the role of diagnostic breast ultrasound performed by nonradiologists in resource-constrained settings. The authors examined 2-year clinical follow-up and outcomes among women who underwent diagnostic breast ultrasound performed by nonradiologist clinicians participating in a breast ultrasound training and mentorship program at a rural Rwandan hospital. METHODS: Imaging findings, management plans, and pathologic results were prospectively collected during the training using a standardized form. Data on follow-up and outcomes for patients receiving breast ultrasound between January 2016 and March 2017 were retrospectively collected through medical record review. RESULTS: Two hundred twenty-nine breast palpable findings (199 patients) met the study's eligibility criteria. Of 104 lesions initially biopsied, 38 were malignant on initial biopsy; 3 lesions were identified as malignant on repeat biopsy. All 34 patients ultimately diagnosed with cancer received initial recommendations for either biopsy or aspiration by trainees. The positive predictive value of trainee biopsy recommendation was 34.8% (95% confidence interval, 24.8%-45.0%). The sensitivity of trainees' biopsy recommendation for identifying malignant lesions was 92.7% (95% confidence interval, 84.2%-100%). Of 46 patients who did not receive biopsy and were told to return for clinical or imaging follow-up, 37.0% did not return. CONCLUSIONS: Trained nonradiologist clinicians in Rwanda successfully identified suspicious breast lesions on diagnostic breast ultrasound. Loss to follow-up was common among patients instructed to return for surveillance, so lower biopsy thresholds, decentralized surveillance, or patient navigation should be considered for patients with low- or intermediate-suspicion lesions.
    • Imaging response assessment for oncology: An algorithmic approach

      Ruchalski, Kathleen; Dewan, Rohit; Sai, Victor; McIntosh, Lacey J.; Braschi-Amirfarzan, Marta (2022-06-07)
      Treatment response assessment by imaging plays a vital role in evaluating changes in solid tumors during oncology therapeutic clinical trials. Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 is the reference standard imaging response criteria and provides details regarding image acquisition, image interpretation and categorical response classification. While RECIST 1.1 is applied for the majority of clinical trials in solid tumors, other criteria and modifications have been introduced when RECIST 1.1 outcomes may be incomplete. Available criteria beyond RECIST 1.1 can be explored in an algorithmic fashion dependent on imaging modality, tumor type and method of treatment. Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST) is available for use with PET/CT. Modifications to RECIST 1.1 can be tumor specific, including mRECIST for hepatocellular carcinoma and mesothelioma. Choi criteria for gastrointestinal stromal tumors incorporate tumor density with alterations to categorical response thresholds. Prostate Cancer Working Group 3 (PCWG3) imaging criteria combine RECIST 1.1 findings with those of bone scans. In addition, multiple response criteria have been created to address atypical imaging responses in immunotherapy.
    • Correlation of von Willebrand factor and platelets with acute ischemic stroke etiology and revascularization outcome: an immunohistochemical study

      Mereuta, Oana Madalina; Gounis, Matthew J.; Puri, Ajit S. (2022-05-20)
      BACKGROUND: Platelets and von Willebrand factor (vWF) are key components of acute ischemic stroke (AIS) emboli. We aimed to investigate the CD42b (platelets)/vWF expression, its association with stroke etiology and the impact these components may have on the clinical/procedural parameters. METHODS: CD42b/vWF immunostaining was performed on 288 emboli collected as part of the multicenter STRIP Registry. CD42b/VWF expression and distribution were evaluated. Student's t-test and chi(2) test were performed as appropriate. RESULTS: The mean CD42b and VWF content in clots was 44.3% and 21.9%, respectively. There was a positive correlation between platelets and vWF (r=0.64, p < 0.001**). We found a significantly higher vWF level in the other determined etiology (p=0.016*) and cryptogenic (p=0.049*) groups compared with cardioembolic etiology. No significant difference in CD42b content was found across the etiology subtypes. CD42b/vWF patterns were significantly associated with stroke etiology (p=0.006*). The peripheral pattern was predominant in atherosclerotic clots (36.4%) while the clustering (patchy) pattern was significantly associated with cardioembolic and cryptogenic origin (66.7% and 49.8%, respectively). The clots corresponding to other determined etiology showed mainly a diffuse pattern (28.1%). Two types of platelets were distinguished within the CD42b-positive clusters in all emboli: vWF-positive platelets were observed at the center, surrounded by vWF-negative platelets. Thrombolysis correlated with a high platelet content (p=0.03*). vWF-poor and peripheral CD42b/vWF pattern correlated with first pass effect (p=0.03* and p=0.04*, respectively). CONCLUSIONS: The vWF level and CD42b/vWF distribution pattern in emboli were correlated with AIS etiology and revascularization outcome. Platelet content was associated with response to thrombolysis.
    • Dual gating myocardial perfusion SPECT denoising using a conditional generative adversarial network

      Sun, Jingzhang; Zhang, Qi; Du, Yu; Zhang, Duo; Pretorius, P. Hendrik; King, Michael A.; Mok, Greta S. P. (2022-05-08)
      PURPOSE: Dual respiratory-cardiac gating reduces respiratory and cardiac motion blur in myocardial perfusion single-photon emission computed tomography (MP-SPECT). However, image noise is increased as detected counts are reduced in each dual gate (DG). We aim to develop a denoising method for dual gating MP-SPECT images using a 3D conditional generative adversarial network (cGAN). METHODS: Twenty extended cardiac-torso phantoms with various (99m) Tc-sestamibi distributions, defect characteristics, and body and organ sizes were used in the simulation, modeling six respiratory and eight cardiac gates (CGs), that is, 48 DGs for ordered subset expectation maximization reconstruction. Twenty clinical (99m) Tc-sestamibi SPECT/CT datasets were re-binned into 7 respiratory gates and 8 CGs, that is, 56 DGs for maximum likelihood expectation maximization reconstruction. We evaluated the use of (i) phantoms' own datasets (patient-specific denoising [PD]) or other phantoms' datasets (cross-patient denoising) for training; (ii) the CG or the static (non-gated [NG]) data as the training references for cGAN; and (iii) cGAN as compared to conventional 3D post-reconstruction filtering, cardiac gating methods, and convolutional neural network. Normalized mean squared error, noise as assessed by normalized standard deviation, spatial blurring measured as the full-width-at-half-maximum of left ventricular wall, ejection fraction, joint correlation histogram, and defect size were analyzed as metrics of image quality. RESULTS: Training using patients' own dataset is superior to conventional training based on other patients' data. Using CG image as training reference provides a better trade-off in terms of noise and image blur as compared to the use of NG. cGAN-CG-PD provides superior performance as compared to other denoising methods for all physical and diagnostic indices evaluated in both simulation and clinical studies. CONCLUSIONS: cGAN denoising is promising for dual gating MP-SPECT based on the metrics mentioned earlier.
    • Intravascular lithotripsy for severely calcified carotid artery stenosis - A new frontier in carotid artery stenting

      Singh, Jasmeet; Kuhn, Anna L.; Massari, Francesco; Elnazeir, Marwa; Kutcher-Diaz, Roberto; Puri, Ajit S. (2022-05-03)
      Carotid stenosis due to severely calcified plaque can pose a significant therapeutic challenge. Extremely calcified scars/stenosis plaques can be challenging from an endovascular treatment perspective as severely calcified lesions are prone to technical failure, stent re-coil and restenosis. Intravascular lithotripsy, approved for treatment of severely calcified coronary lesions, can be used for breaking up the calcium build up in the intimal and medial layers of the vessel wall prior to stenting. This was designated as a breakthrough device innovation by the Food and Drug Administration. This new technique addresses the challenge of the disease without compromising patient safety during the procedure. We here report procedural set-up, execution and early patient follow up from our first use of this emerging technology in a neurointerventional practice setting.
    • Retreatment of Residual and Recurrent Aneurysms After Embolization With the Woven EndoBridge Device: Multicenter Case Series

      Srinivasan, Visish M.; Puri, Ajit S.; Massari, Francesco; Kan, Peter (2022-05-01)
      BACKGROUND: The Woven EndoBridge (WEB) device (Terumno Corp. [parent company of Microvention]) was approved by the U.S. Food and Drug Administration as the first intrasaccular device for intracranial aneurysm treatment in December 2018. Its use has become more common since then, but both trial results and postmarket experiences have raised questions about the efficacy in achieving complete aneurysm obliteration. Retreatment after WEB embolization has not been extensively discussed. OBJECTIVE: To discuss the incidence and retreatment of aneurysms after initial WEB embolization. METHODS: Retrospective review across 13 institutions identified all occurrences of WEB retreatment within neurovascular databases. Details regarding demographics, aneurysm characteristics, treatment considerations, clinical outcomes, and aneurysm occlusion were obtained and analyzed. RESULTS: Thirty aneurysms were retreated in 30 patients in a cohort of 342 WEB-treated aneurysms. The retreatment rate was 8.8%. Endovascular methods were used for 23 cases, and 7 were treated surgically. Two aneurysms presented with rehemorrhage after initial WEB embolization. Endovascular treatments included stent-assisted coiling (12), flow diversion (7), coiling (2), PulseRider (Johnson and Johnson)-assisted coiling (1), and additional WEB placement (1). Surgical treatments included primary clipping (6) and Hunterian ligation (1). There were no major complications within the study group. CONCLUSION: WEB retreatments were successfully performed by a variety of techniques, including stent-assisted coiling, clipping, and flow diversion as the most common. These procedures were performed safely with subsequent obliteration of most aneurysms. The potential need for retreatment of aneurysms should be considered during primary WEB treatments.
    • Comparing treatment outcomes of various intracranial bifurcation aneurysms locations using the Woven EndoBridge (WEB) device

      Adeeb, Nimer; Kuhn, Anna L.; Puri, Ajit S. (2022-04-28)
      BACKGROUND: The Woven EndoBridge (WEB) device has Food and Drug Administration approval for treatment of wide-necked intracranial bifurcation aneurysms. The WEB device has been shown to result in adequate occlusion in bifurcation aneurysms overall, but its usefulness in the individual bifurcation locations has been evaluated separately only in few case series, which were limited by small sample sizes. OBJECTIVE: To compare angiographic and clinical outcomes after treatment of bifurcation aneurysms at various locations, including anterior communicating artery (AComA), anterior cerebral artery (ACA) bifurcation distal to AComA, basilar tip, internal carotid artery (ICA) bifurcation, and middle cerebral artery (MCA) bifurcation aneurysms using the WEB device. METHODS: A retrospective cohort analysis was conducted at 22 academic institutions worldwide to compare treatment outcomes of patients with intracranial bifurcation aneurysms using the WEB device. Data include patient and aneurysm characteristics, procedural details, angiographic and functional outcomes, and complications. RESULTS: A total of 572 aneurysms were included. MCA (36%), AComA (35.7%), and basilar tip (18.9%) aneurysms were most common. The rate of adequate aneurysm occlusion was significantly higher for basilar tip (91.6%) and ICA bifurcation (96.7%) aneurysms and lower for ACA bifurcation (71.4%) and AComA (80.6%) aneurysms (p=0.04). CONCLUSION: To our knowledge, this is the most extensive study to date that compares the treatment of different intracranial bifurcation aneurysms using the WEB device. Basilar tip and ICA bifurcation aneurysms showed significantly higher rates of aneurysm occlusion than other locations.
    • Cross-vender, cross-tracer, and cross-protocol deep transfer learning for attenuation map generation of cardiac SPECT

      Chen, Xiongchao; Pretorius, P. Hendrik; Zhou, Bo; Liu, Hui; Johnson, Karen L.; Liu, Yi-Hwa; King, Michael A.; Liu, Chi (2022-04-26)
      It has been proved feasible to generate attenuation maps (mu-maps) from cardiac SPECT using deep learning. However, this assumed that the training and testing datasets were acquired using the same scanner, tracer, and protocol. We investigated a robust generation of CT-derived mu-maps from cardiac SPECT acquired by different scanners, tracers, and protocols from the training data. We first pre-trained a network using 120 studies injected with (99m)Tc-tetrofosmin acquired from a GE 850 SPECT/CT with 360-degree gantry rotation, which was then fine-tuned and tested using 80 studies injected with (99m)Tc-sestamibi acquired from a Philips BrightView SPECT/CT with 180-degree gantry rotation. The error between ground-truth and predicted mu-maps by transfer learning was 5.13 +/- 7.02%, as compared to 8.24 +/- 5.01% by direct transition without fine-tuning and 6.45 +/- 5.75% by limited-sample training. The error between ground-truth and reconstructed images with predicted mu-maps by transfer learning was 1.11 +/- 1.57%, as compared to 1.72 +/- 1.63% by direct transition and 1.68 +/- 1.21% by limited-sample training. It is feasible to apply a network pre-trained by a large amount of data from one scanner to data acquired by another scanner using different tracers and protocols, with proper transfer learning.
    • Multicenter Study for the Treatment of Sidewall versus Bifurcation Intracranial Aneurysms with Use of Woven EndoBridge (WEB)

      Adeeb, Nimer; Kuhn, Anna L.; Puri, Ajit S. (2022-04-19)
      Background The Woven EndoBridge (WEB) device was explicitly designed for wide-neck intracranial bifurcation aneurysms. Small-scale reports have evaluated the off-label use of WEB devices for the treatment of sidewall aneurysms, with promising outcomes. Purpose To compare the angiographic and clinical outcomes of the WEB device for the treatment of sidewall aneurysms compared with the treatment of bifurcation aneurysms. Materials and Methods A retrospective review of the WorldWideWEB Consortium, a synthesis of retrospective databases spanning from January 2011 to June 2021 at 22 academic institutions in North America, South America, and Europe, was performed to identify patients with intracranial aneurysms treated with the WEB device. Characteristics and outcomes were compared between bifurcation and sidewall aneurysms. Propensity score matching (PSM) was used to match by age, pretreatment ordinal modified Rankin Scale score, ruptured aneurysms, location of aneurysm, multiple aneurysms, prior treatment, neck, height, dome width, daughter sac, and incorporated branch. Results A total of 683 intracranial aneurysms were treated using the WEB device in 671 patients (median age, 61 years [IQR, 53-68 years]; male-to-female ratio, 1:2.5). Of those, 572 were bifurcation aneurysms and 111 were sidewall aneurysms. PSM was performed, resulting in 91 bifurcation and sidewall aneurysms pairs. No significant difference was observed in occlusion status at last follow-up, deployment success, or complication rates between the two groups. Conclusion No significantly different outcomes were observed following the off-label use of the Woven EndoBridge, or WEB, device for treatment of sidewall aneurysms compared with bifurcation aneurysms. The correct characterization of the sidewall aneurysm location, neck angle, and size is crucial for successful treatment and lower retreatment rate.
    • Peer learning in emergency radiology: effects on learning, error identification, and radiologist experience

      Schmidt, Eric; Lo, Hao S.; Saghir, Amina (2022-04-07)
      PURPOSE: We established and evaluated a peer learning program in an emergency radiology (ER) division. Peer learning is an alternative to peer review focusing on non-punitive error reporting to mitigate consequences of inevitable human error. The central component is the peer learning conference, where cases are presented, key teaching points are discussed, and process improvement ideas are solicited. METHODS: We established a prior imaging-based case identification system and a bimonthly remote videoconference where ER faculty discuss 5-15 cases selected for learning or process improvement opportunities. Case identification and conference characteristics were captured. A survey focused on learning and performance outcomes was administered to faculty initially and showed improved scores after 6 months. RESULTS: Cases selected for conference favored perception errors (46%), with great calls (17%) and process improvement (15%) the next most common categories. A variety of anatomical regions were represented, with abdominal (35%) and musculoskeletal (29%) most common. Error detection was improved over peer review. All participants find the system easy to use and prefer peer learning to peer review for learning and process improvement. CONCLUSION: A peer learning program can be successfully implemented within a busy academic emergency radiology division, as evidenced by increasing buy-in and engagement scores over time. When tied to a departmental peer learning infrastructure, interdisciplinary expertise and robust case identification can be leveraged to increase learning opportunities.
    • Acute ischaemic stroke associated with SARS-CoV-2 infection in North America

      Dmytriw, Adam A.; Kuhn, Anna L.; Puri, Ajit S. (2022-04-01)
      BACKGROUND: To analyse the clinical characteristics of COVID-19 with acute ischaemic stroke (AIS) and identify factors predicting functional outcome. METHODS: Multicentre retrospective cohort study of COVID-19 patients with AIS who presented to 30 stroke centres in the USA and Canada between 14 March and 30 August 2020. The primary endpoint was poor functional outcome, defined as a modified Rankin Scale (mRS) of 5 or 6 at discharge. Secondary endpoints include favourable outcome (mRS < /=2) and mortality at discharge, ordinal mRS (shift analysis), symptomatic intracranial haemorrhage (sICH) and occurrence of in-hospital complications. RESULTS: A total of 216 COVID-19 patients with AIS were included. 68.1% (147/216) were older than 60 years, while 31.9% (69/216) were younger. Median [IQR] National Institutes of Health Stroke Scale (NIHSS) at presentation was 12.5 (15.8), and 44.2% (87/197) presented with large vessel occlusion (LVO). Approximately 51.3% (98/191) of the patients had poor outcomes with an observed mortality rate of 39.1% (81/207). Age > 60 years (aOR: 5.11, 95% CI 2.08 to 12.56, p < 0.001), diabetes mellitus (aOR: 2.66, 95% CI 1.16 to 6.09, p=0.021), higher NIHSS at admission (aOR: 1.08, 95% CI 1.02 to 1.14, p=0.006), LVO (aOR: 2.45, 95% CI 1.04 to 5.78, p=0.042), and higher NLR level (aOR: 1.06, 95% CI 1.01 to 1.11, p=0.028) were significantly associated with poor functional outcome. CONCLUSION: There is relationship between COVID-19-associated AIS and severe disability or death. We identified several factors which predict worse outcomes, and these outcomes were more frequent compared to global averages. We found that elevated neutrophil-to-lymphocyte ratio, rather than D-Dimer, predicted both morbidity and mortality.
    • Detection of Pulmonary Congestion in Heart Failure With Preserved Ejection Fraction Using Quantitative Chest CT

      Hatabu, Hiroto; Barile, Maria (2022-04-01)
      Comment on: Jain CC, Tschirren J, Reddy YNV, Melenovsky V, Redfield M, Borlaug BA. Subclinical Pulmonary Congestion and Abnormal Hemodynamics in Heart Failure With Preserved Ejection Fraction. JACC Cardiovasc Imaging. 2022 Apr;15(4):629-637. doi: 10.1016/j.jcmg.2021.09.017. Epub 2021 Nov 17. PMID: 34801461; PMCID: PMC8995316.
    • Downstream Mammary and Extramammary Cascade Services and Spending Following Screening Breast Magnetic Resonance Imaging vs Mammography Among Commercially Insured Women

      Ganguli, Ishani; Keating, Nancy l.; Thakore, Nitya; Lii, Joyce; Raza, Sughra; Pace, Lydia E. (2022-04-01)
      Importance: Increasing use of screening breast magnetic resonance imaging (MRI), including among women at low or average risk of breast cancer, raises concerns about resulting mammary and extramammary cascades (downstream services and new diagnoses) of uncertain value. Objective: To estimate rates of cascade events (ie, laboratory tests, imaging tests, procedures, visits, hospitalizations, and new diagnoses) and associated spending following screening breast MRI vs mammography among commercially insured US women. Design, Setting, and Participants: This cohort study used 2016 to 2018 data from the MarketScan research database (IBM Corporation), which includes claims and administrative data from large US employers and commercial payers. Participants included commercially insured women aged 40 to 64 years without prior breast cancer who received an index bilateral screening breast MRI or mammogram between January 1, 2017, and June 30, 2018. We used propensity scores based on sociodemographic, clinical, and utilization variables to match MRI recipients to mammogram recipients in each month of index service use. Data were analyzed from October 8, 2020, to October 28, 2021. Exposures: Breast MRI vs mammography. Main Outcomes and Measures: Mammary and extramammary cascade event rates and associated total and patient out-of-pocket spending in the 6 months following the index test. Results: In this study, 9208 women receiving breast MRI were matched with 9208 women receiving mammography (mean [SD] age, 51.4 [6.7] years). Compared with mammogram recipients, breast MRI recipients had 39.0 additional mammary cascade events per 100 women (95% CI, 33.7-44.2), including 5.0 additional imaging tests (95% CI, 3.8-6.2), 17.3 additional procedures (95% CI, 15.5-19.0), 13.0 additional visits (95% CI, 9.4-17.2), 0.34 additional hospitalizations (95% CI, 0.18-0.50), and 3.0 additional new diagnoses (95% CI, 2.5-3.6). For extramammary cascades, breast MRI recipients had 19.6 additional events per 100 women (95% CI, 8.6-30.7) including 15.8 additional visits (95% CI, 10.2-21.4) and no statistically significant differences in other events. Breast MRI recipients had higher total spending for mammary events ($564 more per woman; 95% CI, $532-$596), extramammary events ($42 more per woman; 95% CI, $16-$69), and overall ($1404 more per woman; 95% CI, $1172-$1636). They also had higher overall out-of-pocket spending ($31 more per woman; 95% CI, $6-$55). Conclusions and Relevance: In this cohort study of commercially insured women, breast MRI was associated with more mammary and extramammary cascade events and spending relative to mammography. These findings can inform cost-benefit assessments and coverage policies to ensure breast MRI is reserved for patients for whom benefits outweigh harms.
    • Traumatic Intracranial Hemorrhage on CT After Ground-Level Fall in Adult Patients on Antithrombotic Therapy: A Retrospective Case-Control Study

      Vardar, Zeynep; Lo, Hao S.; Mariyampillai, Matthew; Kotecha, Hemang M. (2022-03-23)
      Background: Antithrombotic medications may increase risk and severity of traumatic intracranial hemorrhage (tICH) after minor head trauma. Objective: To determine the frequency, distribution, and clinical course of tICH in patients on antithrombotic therapy who present with good neurological status after ground-level fall. Methods: This retrospective study included 1630 patients (mean age 80+/-12 years; 693 female, 937 male) who underwent head CT after presenting to the emergency department with ground-level fall between January 1 and December 31, 2020, and with Glasgow Coma Scale > /=14 and no focal neurological deficit. Patients with tICH were identified based on the clinical reports. In patients with tICH, images from initial head CT examinations were reviewed for tICH characteristics, images from follow-up head CT examinations (performed within 24 hours) were reviewed for hematoma expansion, and clinical outcomes were extracted from medical records. Patients on antithrombotic therapy and control patients (not on antithrombotic therapy) were compared. Results: The antithrombotic therapy group included 954 patients (608 anticoagulant, 226 antiplatelet, 120 both); the control group included 676 patients. A total of 63 (3.9%; 95% CI, 2.9-4.8%) patients had tICH. The antithrombotic therapy and control groups were not significantly different in terms of frequency of tICH (4.4% vs 3.1%, p = .24), midline shift (10.0% vs 7.1%, p = .76) or regional mass effect (33.3% vs 14.3%, p = .19) on initial CT. Hematoma expansion on follow-up CT occurred in 11/42 (26.2%) patients in the antithrombotic group and 1/21 (4.8%) patient in the control group (p = .04). Two patients required neurosurgical intervention, and three patients died within 30 days related to tICH; all such patients were on antithrombotic therapy. Conclusion: Antithrombotic therapy use was not associated with increased frequency of tICH, although was associated with increased frequency of hematoma expansion at follow-up. Clinical impact: The findings suggest, in patients with good neurological status after ground-level fall, application of a similar strategy for selecting patients for initial head CT regardless of antithrombotic therapy use; if initial head CT shows tICH, early follow-up head CT should be systematically performed in those on antithrombotic therapy though possibly deferred in other patients.
    • Novel Oxygen Carrier Slows Infarct Growth in Large Vessel Occlusion Dog Model Based on Magnetic Resonance Imaging Analysis

      Shazeeb, Mohammed S.; King, Robert M.; Anagnostakou, Vania; Vardar, Zeynep; Kraitem, Afif M.; Kolstad, Josephine; Raskett, Christopher M.; Le Moan, Natacha; Winger, Jonathan A.; Kelly, Lauren; et al. (2022-03-21)
      BACKGROUND: Tissue hypoxia plays a critical role in the events leading to cell death in ischemic stroke. Despite promising results in preclinical and small clinical pilot studies, inhaled oxygen supplementation has not translated to improved outcomes in large clinical trials. Moreover, clinical observations suggest that indiscriminate oxygen supplementation can adversely affect outcome, highlighting the need to develop novel approaches to selectively deliver oxygen to affected regions. This study tested the hypothesis that intravenous delivery of a novel oxygen carrier (Omniox-Ischemic Stroke [OMX-IS]), which selectively releases oxygen into severely ischemic tissue, could delay infarct progression in an established canine thromboembolic large vessel occlusion stroke model that replicates key dynamics of human infarct evolution. METHODS: After endovascular placement of an autologous clot into the middle cerebral artery, animals received OMX-IS treatment or placebo 45 to 60 minutes after stroke onset. Perfusion-weighted magnetic resonance imaging was performed to define infarct progression dynamics to stratify animals into fast versus slow stroke evolvers. Serial diffusion-weighted magnetic resonance imaging was performed for up to 5 hours to quantify infarct evolution. Histology was performed postmortem to confirm final infarct size. RESULTS: In fast evolvers, OMX-IS therapy substantially slowed infarct progression (by approximately 1 hour, P < 0.0001) and reduced the final normalized infarct volume as compared to controls (0.99 versus 0.88, control versus OMX-IS drug, P < 0.0001). Among slow evolvers, OMX-IS treatment delayed infarct progression by approximately 45 minutes; however, this did not reach statistical significance (P=0.09). The final normalized infarct volume also did not show a significant difference (0.93 versus 0.95, OMX-IS drug versus control, P=0.34). Postmortem histologically determined infarct volumes showed excellent concordance with the magnetic resonance imaging defined ischemic lesion volume (bias: 1.33% [95% CI, -15% to 18%). CONCLUSIONS: Intravenous delivery of a novel oxygen carrier is a promising approach to delay infarct progression after ischemic stroke, especially in treating patients with large vessel occlusion stroke who cannot undergo definitive reperfusion therapy within a timely fashion.
    • Interacting-heads motif explains the X-ray diffraction pattern of relaxed vertebrate skeletal muscle

      Koubassova, Natalia A.; Tsaturyan, Andrey K.; Bershitsky, Sergey Y.; Ferenczi, Michael A.; Padron, Raul A.; Craig, Roger W. (2022-03-19)
      Electron microscopy (EM) shows that myosin heads in thick filaments isolated from striated muscles interact with each other and with the myosin tail under relaxing conditions. This "interacting-heads motif" (IHM) is highly conserved across the animal kingdom and is thought to be the basis of the super-relaxed state. However, a recent X-ray modeling study concludes, contrary to expectation, that the IHM is not present in relaxed intact muscle. We propose that this conclusion results from modeling with a thick filament 3D reconstruction in which the myosin heads have radially collapsed onto the thick filament backbone, not from absence of the IHM. Such radial collapse, by about 3-4 nm, is well established in EM studies of negatively stained myosin filaments, on which the reconstruction was based. We have tested this idea by carrying out similar X-ray modeling and determining the effect of the radial position of the heads on the goodness of fit to the X-ray pattern. We find that, when the IHM is modeled into a thick filament at a radius 3-4 nm greater than that modeled in the recent study, there is good agreement with the X-ray pattern. When the original (collapsed) radial position is used, the fit is poor, in agreement with that study. We show that modeling of the low-angle region of the X-ray pattern is relatively insensitive to the conformation of the myosin heads but very sensitive to their radial distance from the filament axis. We conclude that the IHM is sufficient to explain the X-ray diffraction pattern of intact muscle when placed at the appropriate radius.
    • Prospective study on embolization of intracranial aneurysms with the pipeline device (PREMIER study): 3-year results with the application of a flow diverter specific occlusion classification

      Hanel, Ricardo A.; Puri, Ajit S. (2022-03-15)
      BACKGROUND: The pipeline embolization device (PED; Medtronic) has presented as a safe and efficacious treatment for small- and medium-sized intracranial aneurysms. Independently adjudicated long-term results of the device in treating these lesions are still indeterminate. We present 3-year results, with additional application of a flow diverter specific occlusion scale. METHODS: PREMIER (prospective study on embolization of intracranial aneurysms with pipeline embolization device) is a prospective, single-arm trial. Inclusion criteria were patients with unruptured wide-necked intracranial aneurysms < /=12 mm. Primary effectiveness (complete aneurysm occlusion) and safety (major neurologic event) endpoints were independently monitored and adjudicated. RESULTS: As per the protocol, of 141 patients treated with a PED, 25 (17.7%) required angiographic follow-up after the first year due to incomplete aneurysm occlusion. According to the Core Radiology Laboratory review, three (12%) of these patients progressed to complete occlusion, with an overall rate of complete aneurysm occlusion at 3 years of 83.3% (115/138). Further angiographic evaluation using the modified Cekirge-Saatci classification demonstrated that complete occlusion, neck residual, or aneurysm size reduction occurred in 97.1%. The overall combined safety endpoint at 3 years was 2.8% (4/141), with only one non-debilitating major event occurring after the first year. There was one case of aneurysm recurrence but no cases of delayed rupture in this series. CONCLUSIONS: The PED device presents as a safe and effective modality in treating small- and medium-sized intracranial aneurysms. The application of a flow diverter specific occlusion classification attested the long-term durability with higher rate of successful aneurysm occlusion and no documented aneurysm rupture. TRIAL REGISTRATION: NCT02186561.