Are hemodynamics responsible for inflammatory changes in venous vessel walls? A quantitative study of wall-enhancing intracranial arteriovenous malformation draining veins.

OBJECTIVE: Signal enhancement of vascular walls on vessel wall MRI might be a biomarker for inflammation. It has been theorized that contrast enhancement on vessel wall imaging (VWI) in draining veins of intracranial arteriovenous malformations (AVMs) may be associated with disease progression and development of venous stenosis. The aim of this study was to investigate the relationship between vessel wall enhancement and hemodynamic stressors along AVM draining veins. METHODS: Eight AVM patients with 15 draining veins visualized on VWI were included. Based on MR venography data, patient-specific 3D surface models of the venous anatomy distal to the nidus were segmented. The enhanced vascular wall regions were manually extracted and mapped onto the venous surface models after registration of image data. Using image-based blood flow simulations applying patient-specific boundary conditions based on phase-contrast quantitative MR angiography, hemodynamics were investigated in the enhanced vasculature. For the shear-related parameters, time-averaged wall shear stress (TAWSS), oscillatory shear index (OSI), and relative residence time (RRT) were calculated. Velocity, oscillatory velocity index (OVI), and vorticity were extracted for the intraluminal flow-related hemodynamics. RESULTS: Visual observations demonstrated overlap of enhancement with local lower shear stresses resulting from decreased velocities. Thus, higher RRT values were measured in the enhanced areas. Furthermore, nonenhancing draining veins showed on average slightly higher flow velocities and TAWSS. Significant decreases of 55% (p = 0.03) for TAWSS and of 24% (p = 0.03) for vorticity were identified in enhanced areas compared with near distal and proximal domains. Velocity magnitude in the enhanced region showed a nonsignificant decrease of 14% (p = 0.06). Furthermore, increases were present in the OSI (32%, p = 0.3), RRT (25%, p = 0.15), and OVI (26%, p = 0.3) in enhanced vessel sections, although the differences were not significant. CONCLUSIONS: This novel multimodal investigation of hemodynamics in AVM draining veins allows for precise prediction of occurring shear- and flow-related phenomena in enhanced vessel walls. These findings may suggest low shear to be a local predisposing factor for venous stenosis in AVMs.

Vessel wall imaging and quantitative flow assessment in arteriovenous malformations: A feasibility study.

INTRODUCTION: Cerebral arteriovenous malformations (AVMs) carry a rupture rate of 2-3% per year. Several architectural factors may influence rupture rate, and a recently theorized model of AVMs describes the influence of vessel wall inflammation. A novel imaging modality, vessel wall imaging (VWI), has been developed to view inflammatory processes in vessel wall foci but has not yet been examined in AVMs, which is the aim of this study. METHODS: This retrospective review studies prospectively collected data on patients with ruptured and unruptured AVMs between 2019 and 2021. Inclusion criteria included adult patients (≥18 years) with radiographically diagnosed AVM who underwent VWI. Charts were reviewed for medical history, clinical presentation, hospital course, discharge condition, and follow-up. Angioarchitectural features, blood flow, and VWI were compared in patients with and without hemorrhagic patients. RESULTS: Nine patients underwent VWI, mean age 37.7 ± 9.9 years. Four presented with hemorrhage (44.4%). Seven (77.7%) received glue embolization and 6 (66.7%) underwent surgical resection. All patients (4/4) with a history of hypertension presented with hemorrhage (p = 0.0027). Size and Spetzler-Martin grade were not associated with hemorrhage (p = 0.47, p = 0.59). Net AVM flow was higher in patients presenting with hemorrhage, although nonsignificant (p = 0.19). With VWI, 3 (75%) hemorrhagic AVMs showed visible nidus and draining veins, and all three demonstrated positive post-contrast wall enhancement in at least one of their draining veins; conversely, of fivenonhemorrhagic AVMs, only 2 (40%) demonstrated post-contrast wall enhancement in any draining vein (p = 0.090). CONCLUSION: This pilot study successfully demonstrated capture of venous walls in AVMs using VWI. In this study, draining vein enhancement occurred more often in hemorrhagic AVM and in those with higher venous volumetric flow.

Impact of cerebral aneurysm size on distal intracranial hemodynamics and changes following flow diversion.

BACKGROUND: The impact of cerebral aneurysm size on distal intracranial hemodynamics such as arterial pressure and Pulsatility Index is not completely understood, either before or after flow diversion. OBJECTIVE: The aim of the study is to assess the impact of aneurysm size on distal Pulsatility Index and pressure before and after flow diversion. METHODS: From December 2015, prospective measurement of middle cerebral artery pressure and Pulsatility Index was performed in consecutive patients with unruptured cerebral aneurysms in the cavernous to communicating segments of the internal carotid artery, which were treated with single flow diversion. Pressure and Pulsatility Index were recorded at the M1-segment ipsilateral to the cerebral aneurysm. Ratio of middle cerebral artery to radial arterial pressure (pressure ratio) was calculated to control for variations in systemic blood pressure. Correlations between aneurysm size and pressure ratio and Pulsatility Index were assessed before and after treatment. RESULTS: A total of 28 aneurysms were treated. The mean aneurysm size was 7.2 mm. Aneurysm size correlated linearly with systolic pressure ratio (1% pressure ratio increase per mm aneurysm size increase, P = 0.002, r2 = 0.33), mean pressure ratio (0.6% per mm, P = 0.03, r2 = 0.17) and Pulsatility Index (5% Pulsatility Index increase per mm, P = 0.003, r2 = 0.43). After flow diversion, aneurysm size preserved a linear correlation with the systolic pressure ratio (1% per mm, P = 0.004, r2 = 0.28), but not with the mean pressure ratio (0.4% per mm, P = 0.15, r2 < 0.1) or Pulsatility Index (0.3% per mm, P = 0.78, r2 < 0.1). CONCLUSION: Aneurysm size affects distal hemodynamics: patients with larger aneurysms have increased systolic and mean pressure ratio, and increased Pulsatility Index. After flow diversion, mean pressure ratio and Pulsatility Index no longer associate with the aneurysm size, suggesting an effect of the flow diversion also on distal intracranial hemodynamics.

Crusted Scabies Infection in the Setting of Chronic Steroid and Omalizumab Use.

Scabies infection is a very common skin disease that occurs due to infestation with the Sarcoptes scabei mite. Typically, it results in intensely pruritic papules and excoriations in the webs of the hand, groin, or axilla, and remains limited in its spread. In rare cases, the disease can become diffuse and progress to crusted or nodular subtypes. Here, we report the case of crusted scabies infestation in a 69-year-old male who presented with a diffuse pruritic, erythematous, and petechial rash. His medical history was significant for severe idiopathic urticaria treated with omalizumab. Before starting omalizumab, the patient was self-medicating for several months with corticosteroids obtained through his veterinary practice to alleviate symptoms. His presentation was complicated by immune thrombocytopenic purpura and muscle weakness, likely secondary to omalizumab and corticosteroid use, respectively. The patient underwent an extensive rheumatologic workup until skin biopsy confirmed the underlying etiology as crusted scabies infestation. He was treated with ivermectin and weekly 5% permethrin skin cream with great improvement of his rash; however, unfortunately, he succumbed to bacterial sepsis. Scabies infestation can masquerade as a manifestation of other systemic diseases and is often misdiagnosed. As this case illustrates, initial misdiagnosis and subsequent treatment with immunosuppressive drug regimens can cause preventable, but potentially fatal, concomitant superinfections.

Morbidity and mortality associated with sequential flow reduction embolization technique of cerebral arteriovenous malformations using n-butyl cyanoacrylate.

BACKGROUND: Endovascular embolization of cerebral arteriovenous malformations (AVM) with liquid n-butyl cyanoacrylate (n-BCA) serves multiple purposes including AVM occlusion and flow reduction in preparation for other treatment modalities. The objective was to study the clinical, structural, and angiographic factors affecting complications associated with AVM treatment by sequential n-BCA embolizations for nidal occlusion versus quantitative flow reduction in preparation for surgical resection or radiosurgery. METHODS: We performed a retrospective review of all patients who underwent endovascular embolization of cerebral AVM at our institution between 1998 and 2019, during which time the technique of traditional embolization evolved to a strategy of targeted sequential flow reduction guided by serial flow imaging based on quantitative magnetic resonance angiography, in conjunction with a shift away from nidal penetration. RESULTS: Among 251 patients, 47.8% of patients presented with ruptured AVM. On average, each patient underwent 2.4 embolizations, for a total of 613 sessions. Major morbidity related to embolization occurred in 18 (7.2%) patients, but this occurred disproportionately in the traditional embolization strategy (n=16, 8%) in contrast with the flow-targeting strategy (n=2, 3.8%). Four patients (1.6%) died in the overall group, and these all occurred with the traditional embolization strategy (2% of 199 patients); no deaths occurred in the flow-targeting strategy (n=52). CONCLUSION: Embolization with n-BCA targeted to sequential flow reduction and feeder occlusion with limited nidal penetration prior to definitive surgical or radiosurgical treatment can be safely performed with low overall morbidity and mortality.

The Oncopig Cancer Model: An Innovative Large Animal Translational Oncology Platform.

Despite an improved understanding of cancer molecular biology, immune landscapes, and advancements in cytotoxic, biologic, and immunologic anti-cancer therapeutics, cancer remains a leading cause of death worldwide. More than 8.2 million deaths were attributed to cancer in 2012, and it is anticipated that cancer incidence will continue to rise, with 19.3 million cases expected by 2025. The development and investigation of new diagnostic modalities and innovative therapeutic tools is critical for reducing the global cancer burden. Toward this end, transitional animal models serve a crucial role in bridging the gap between fundamental diagnostic and therapeutic discoveries and human clinical trials. Such animal models offer insights into all aspects of the basic science-clinical translational cancer research continuum (screening, detection, oncogenesis, tumor biology, immunogenicity, therapeutics, and outcomes). To date, however, cancer research progress has been markedly hampered by lack of a genotypically, anatomically, and physiologically relevant large animal model. Without progressive cancer models, discoveries are hindered and cures are improbable. Herein, we describe a transgenic porcine model-the Oncopig Cancer Model (OCM)-as a next-generation large animal platform for the study of hematologic and solid tumor oncology. With mutations in key tumor suppressor and oncogenes, TP53R167H and KRASG12D , the OCM recapitulates transcriptional hallmarks of human disease while also exhibiting clinically relevant histologic and genotypic tumor phenotypes. Moreover, as obesity rates increase across the global population, cancer patients commonly present clinically with multiple comorbid conditions. Due to the effects of these comorbidities on patient management, therapeutic strategies, and clinical outcomes, an ideal animal model should develop cancer on the background of representative comorbid conditions (tumor macro- and microenvironments). As observed in clinical practice, liver cirrhosis frequently precedes development of primary liver cancer or hepatocellular carcinoma. The OCM has the capacity to develop tumors in combination with such relevant comorbidities. Furthermore, studies on the tumor microenvironment demonstrate similarities between OCM and human cancer genomic landscapes. This review highlights the potential of this and other large animal platforms as transitional models to bridge the gap between basic research and clinical practice.