Transcranial histotripsy parameter study in primary and metastatic murine brain tumor models.

OBJECTIVE: This study investigated the effect of various histotripsy dosages on tumor cell kill and associated bleeding in two murine brain tumor models (glioma [Gl261] and lung metastasis [LL/2-Luc2]). METHODS AND MATERIALS: GL261 or LL/2-Luc2 cells were cultured and implanted into the brains of C57BL/6 mice. Histotripsy (1-cycle pulses, 5 Hz PRF, 30 MPa-P) was performed using a 1 MHz transducer for five different dosages for each cell line: 5, 20 or 200 pulses per location (PPL) at a single treatment point, or 5 or 10-20 PPL at multiple treatment points. MRI, bioluminescence imaging and histology were used to assess tumor ablation and treatment effects within 4-6 h post-treatment. RESULTS: All treatment groups resulted in a reduction of BLI intensity for the LL/2-Luc2 tumors, with significant signal reductions for the multi-point groups. The average pre-/post-treatment BLI flux (photons/s, ×108) for the different treatment groups were: 4.39/2.19 (5 PPL single-point), 5.49/1.80 (20 PPL single-point), 3.86/1.73 (200 PPL single-point), 2.44/1.11 (5 PPL multi-point) and 5.85/0.80 (10 PPL multi-point). MRI and H&E staining showed increased tumor damage and hemorrhagic effects with increasing histotripsy dose for both GL261 and LL/2-Luc2 tumors, but the increase in tumor damage was diminished beyond 10-20 PPL for single-point treatments and outweighed by increased hemorrhage. In general, hemorrhage was confined to be within 1 mm of the treatment boundary for all groups. CONCLUSIONS: Our results suggest that a lower number of histotripsy pulses at fewer focal locations can achieve substantial tumor kill while minimizing hemorrhage.

Comparing internal versus external carotid artery branch delivery of intraarterial chemotherapy for the treatment of retinoblastoma.

PURPOSE: The goal of this study was to compare the efficacy of intraarterial chemotherapy (IAC) for retinoblastoma delivered via the ophthalmic artery (OA) division of the internal carotid artery (ICA) versus alternative branches of the external carotid artery (ECA). METHODS: We performed a retrospective chart review of patients receiving IAC for retinoblastoma at a single institution. Subjects were divided into three groups: those that received IAC solely through the OA branch of the ICA, those that initially received IAC through the OA branch of the ICA but were later switched to the ECA, and those that only received IAC through the ECA. The main outcomes compared included globe salvage rate and reduction in tumor thickness and size. RESULTS: A total of 30 eyes from 26 patients were included. A total of 91 (58%) sessions of IAC were performed through the OA division of the ICA and 65 (42%) were performed through branches of the ECA. Eleven eyes (37%) solely received IAC through the OA branch of the ICA, 16 eyes (53%) were converted to ECA treatment, and 3 eyes solely received IAC through branches of the ECA. Statistical analysis did not show any significant difference in globe salvage rate or reduction in tumor thickness and size. CONCLUSION: The use of alternative approaches for IAC when the OA branch of the ICA catheterization is not feasible allows for safe continued delivery of highly effective IAC, leading to similar outcomes in terms of globe salvage and reduction in tumor size.

The potential of 3D models and augmented reality in teaching cross-sectional radiology.

What was the educational challenge?The complexity and variability of cross-sectional imaging present a significant challenge in imparting knowledge of radiologic anatomy to medical students.What was the solution?Recent advancements in three-dimensional (3D) segmentation and augmented reality (AR) technology provide a promising solution. These advances allow for the creation of interactive, patient-specific 3D/AR models which incorporate multiple imaging modalities including MRI, CT, and 3D rotational angiography can help trainees understand cross-sectional imaging.How was the solution implemented?To create the model, DICOM files of patient scans with slice thicknesses of 1 mm or less are exported to a computer and imported to 3D Slicer for registration. Once registered, the files are segmented with Vitrea software utilizing thresholding, region growing, and edge detection. After the creation of the models, they are then imported to a web-based interactive viewing platform and/or AR application.What lessons were learned that are relevant to a wider global audience?Low-resource 3D/AR models offer an accessible and intuitive tool to teach radiologic anatomy and pathology. Our novel method of creating these models leverages recent advances in 3D/AR technology to create a better experience than traditional high and low-resource 3D/AR modeling techniques. This will allow trainees to better understand cross-sectional imaging.What are the next steps?The interactive and intuitive nature of 3D and AR models has the potential to significantly improve the teaching and presentation of radiologic anatomy and pathology to a medical student audience. We encourage educators to incorporate 3D segmentation models and AR in their teaching strategies.

Mechanical Thrombectomy Improves Outcome for Large Vessel Occlusion Stroke after Cardiac Surgery.

BACKGROUND: Stroke is a feared complication of cardiac surgery. Modern clot-retrieval techniques provide effective treatment for large vessel occlusion (LVO) strokes. The purpose of this study was to 1) report the incidence of LVO stroke after cardiac surgery at a large academic center, and 2) describe outcomes of postoperative LVO strokes. METHODS: All patients experiencing stroke within 30 days after undergoing cardiac surgery at a single center in 2014-2018 were reviewed. LVOs were identified through review of imaging and medical records, and their characteristics and clinical courses were examined. RESULTS: Over the study period, 7,112 cardiac surgeries, including endovascular procedures, were performed. Acute ischemic stroke within 30 days after surgery was noted in 163 patients (2.3%). Among those with a stroke, 51/163 (31.3%) had a CTA or MRA, and 15/163 (9.2%) presented with LVO stroke. For all stroke patients, the median time from surgery to stroke was 2 days (interquartile range, IQR, 0-6 days), and for patients with LVO, the median time from surgery to stroke was 4 days (IQR 0-6 days). The overall rate of postoperative LVO was 0.2% (95% CI 0.1-0.4%), though only 6/15 received thrombectomy. LVO patients receiving thrombectomy were significantly more likely to return to independent living compared to those managed medically (n = 4/6, 66.6% for mechanical thrombectomy vs. n = 0/9, 0% for medical management, P = .01). Of the 9 patients who did not get thrombectomy, 6 may currently be candidates for thrombectomy given new expanded treatment windows. CONCLUSIONS: The rate of LVO after cardiac surgery is low, though substantially elevated above the general population, and the majority do not receive thrombectomy currently. Patients receiving thrombectomy had improved neurologic outcomes compared to patients managed medically. Optimized postoperative care may increase the rate of LVO recognition, and cardiac surgery patients and their caregivers should be aware of this effective therapy.

Endovascular Treatment of Arteriovenous Malformations of the Head and Neck: Focus on the Yakes Classification and Outcomes.

PURPOSE: To evaluate endovascular treatment of head and neck arteriovenous malformations (AVMs) based on the Yakes AVM classification and correlate treatment approach with clinical and angiographic outcomes. MATERIALS AND METHODS: A retrospective single-center study was performed in patients who underwent endovascular treatment of head and neck AVMs between January 2005 and December 2017. Clinical and operative records, imaging, and postoperative courses of patients were reviewed. Clinical stage was determined according to the Schobinger classification. AVM architecture and treatment approaches were determined according to the Yakes classification. Primary outcomes were clinical and angiographic treatment success rates and complication rates, with analysis according to the Yakes classification. RESULTS: A total of 29 patients (15 females) were identified, with a mean age of 30.6 years. Downgrading of the Schobinger clinical classification was achieved in all patients. Lesions included 8 Yakes type IIa, 5 type IIb, 1 type IIIa and IIIb, and 14 type IV. Lesions were treated using an intra-arterial, nidal, or transvenous approach, using ethanol and liquid embolic agents. Arteriovenous shunt eradication of >90% was achieved in 22 of 28 patients (79%), including 9 of 13 (69%) of Yakes type IV lesions and 13 of 15 (87%) of the other types. There were 5 significant complications in 79 procedures (6%), including 4 of 50 (8%) in Yakes type IV lesions. CONCLUSIONS: Schobinger stage was downgraded in all patients. Arteriovenous shunt eradication of >90% was achieved in most patients. Yakes type IV lesions required more sessions, and shunt eradication was higher in the Yakes II and III groups.

Minocycline Effects on Intracerebral Hemorrhage-Induced Iron Overload in Aged Rats: Brain Iron Quantification With Magnetic Resonance Imaging.

BACKGROUND AND PURPOSE: Brain iron overload is a key factor causing brain injury after intracerebral hemorrhage (ICH). This study quantified brain iron levels after ICH with magnetic resonance imaging R2* mapping. The effect of minocycline on iron overload and ICH-induced brain injury in aged rats was also determined. METHODS: Aged (18 months old) male Fischer 344 rats had an intracerebral injection of autologous blood or saline, and brain iron levels were measured by magnetic resonance imaging R2* mapping. Some ICH rats were treated with minocycline or vehicle. The rats were euthanized at days 7 and 28 after ICH, and brains were used for immunohistochemistry and Western blot analyses. Magnetic resonance imaging (T2-weighted, T2* gradient-echo, and R2* mapping) sequences were performed at different time points. RESULTS: ICH-induced brain iron overload in the perihematomal area could be quantified by R2* mapping. Minocycline treatment reduced brain iron accumulation, T2* lesion volume, iron-handling protein upregulation, neuronal cell death, and neurological deficits (P<0.05). CONCLUSIONS: Magnetic resonance imaging R2* mapping is a reliable and noninvasive method, which can quantitatively measure brain iron levels after ICH. Minocycline reduced ICH-related perihematomal iron accumulation and brain injury in aged rats.

Horner Syndrome as the Only Focal Neurologic Manifestation of Hypothalamic Hemorrhage.

A 70-year-old woman suffered an anterior dorsal hypothalamic hemorrhage that caused an ipsilateral Horner syndrome (HS) as the only focal neurologic manifestation. This is only the second reported case of hypothalamic hemorrhage producing HS. Because HS was the sole focal neurologic manifestation, its confirmation with topical apraclonidine drops was a valuable clue toward prompt localization of the patient's confusional state.

An integrated multidisciplinary algorithm for the management of spinal metastases: an International Spine Oncology Consortium report.

Spinal metastases are becoming increasingly common because patients with metastatic disease are living longer. The close proximity of the spinal cord to the vertebral column limits many conventional therapeutic options that can otherwise be used to treat cancer. In response to this problem, an innovative multidisciplinary approach has been developed for the management of spinal metastases, leveraging the capabilities of image-guided stereotactic radiosurgery, separation surgery, vertebroplasty, and minimally invasive local ablative approaches. In this Review, we discuss the variables that should be considered during the management of these patients and review the role of each discipline and their respective management options to provide optimal care. This work is synthesised into a practical algorithm to aid clinicians in the management of patients with spinal metastasis.

Use of the Pipeline embolization device in the treatment of iatrogenic intracranial vascular injuries: a bi-institutional experience.

OBJECTIVE Flow-diverting devices have been used for the treatment of complex intracranial vascular pathology with success, but the role of these devices in treating iatrogenic intracranial vascular injuries has yet to be clearly defined. Here, the authors report their bi-institutional experience with the use of the Pipeline embolization device (PED) for the treatment of iatrogenic intracranial vascular injuries. METHODS The authors reviewed a retrospective cohort of patients with iatrogenic injuries to the intracranial vasculature that were treated with the PED between 2012 and 2016. Data collection included demographic data, indications for treatment, number and sizes of PEDs used, and immediate and follow-up angiographic and clinical outcomes. RESULTS Four patients with a mean age of 47.5 years (range 18-63 years) underwent PED placement for iatrogenic vessel injuries. In 3 patients, the intracranial internal carotid artery (ICA) was injured during transnasal tumor resection. In 1 patient, a basilar apex injury occurred during endoscopic third ventriculostomy. Three patients had a pseudoaneurysm as a result of vessel injury, and 1 patient had frank ICA laceration and extravasation. All 3 pseudoaneurysms were successfully treated with PED deployment. The ICA laceration was refractory to PED placement, and the vessel was subsequently occluded endovascularly. All 4 patients had a good clinical outcome (modified Rankin Scale score of 0 or 1). CONCLUSIONS The use of the PED is feasible in the management of iatrogenic pseudoaneurysms of the intracranial vasculature. In cases of frank vessel perforation, an alternative strategy such as covered stent placement should be considered. Endovascular or surgical vessel occlusion remains the definitive treatment in cases of refractory hemorrhage.

Neurovascular emergencies: imaging diagnosis and neurointerventional treatment.

Neurovascular emergencies, consisting of acute ischemic stroke, non-traumatic aneurysmal subarachnoid hemorrhage, arteriovenous malformation, dural arteriovenous fistula, and carotid- cavernous fistula, can have an acute presentation to the emergency department. Radiologists should have an understanding of these processes and their imaging findings in order to provide a prompt and accurate diagnosis. Neurointerventional radiology plays a critical role in providing additional diagnostic information and potentially curative treatment. Understanding the grading scales used to evaluate and prognosticate these neurovascular emergencies can help expedite management for best possible patient outcomes.

Endovascular Treatment of Noncavernous Dural Arteriovenous Fistulas: Analysis of Outcomes with and without Ethylene Vinyl Alcohol.

OBJECTIVE: Noncavernous dural arteriovenous fistulas (DAVFs) are uncommon lesions that can be treated from an endovascular approach using various embolic materials. The purpose of this study was to evaluate our outcomes for endovascular treatment of DAVFs with and without the use of ethylene vinyl alcohol (EVOH). METHODS: We performed a retrospective analysis of 65 patients treated for DAVF at our institution from January 1995 to May 2015. Lesions were classified as aggressive or benign, based on angiography according to Cognard classification. Demographic data, medical comorbidities, presenting symptoms, treatment modality, treatment outcomes, and complications were evaluated for each group. Primary outcome was defined as angiographic occlusion for an aggressive DAVF, and resolution of clinical symptoms for a benign DAVF. RESULTS: The primary outcome was met in 47 (82.5%) of 57 cases with endovascular therapy alone; 23 (69.7%) of 33 aggressive fistulas; and 24 (100.0%) of 24 benign fistulas. There was a 5% overall complication rate. The primary outcome was achieved via endovascular approach in 80.0% (24 of 30) of cases with EVOH, and 85.2% (23 of 27) of cases without EVOH (P = .73). There was a 6% complication rate for procedures using EVOH versus 3% for cases without EVOH (P = 1.00), a 13% clinical recurrence rate for cases using EVOH compared to .0% when EVOH was not used (P = .24), and no angiographic recurrences in either group (P = 1). There were no procedure-related mortalities. CONCLUSIONS: Endovascular treatment of DAVFs has a high success rate and low complication rate. Our experience demonstrated no difference in outcomes between lesions treated with EVOH and those treated without EVOH.

Penetrating Head Injury by a Nail Gun: Case Report, Review of the Literature, and Management Considerations.

Our objective is to discuss penetrating head injuries (PHIs) which, although rare, lead to considerable morbidity and mortality. One of the most significant culprits of PHI is the nail gun, which was introduced in 1959 and has gained substantial popularity. We describe our successful strategy for removing an 8-cm nail that penetrated through the orbit and middle cranial fossa, with the tip lodged within the posterior fossa. Vascular imaging and balloon test occlusion are imperative in circumstances where vessel sacrifice is necessary. In addition, positioning of balloons within large vessels that are in close proximity to the penetrating object is necessary to control bleeding that may occur during removal of the object. It is of paramount importance to have a multidisciplinary team participating in the management and eventual removal of foreign objects within the intracranial compartment. Included is a review of the literature and a discussion on management approaches to such injuries.

Perihematomal Cerebral Tissue Iron Quantification on MRI Following Intracerebral Hemorrhage in Two Human Subjects: Proof of Principle.

Spontaneous intracranial hemorrhage (ICH) is a common hemorrhagic stroke subtype with significant neurological sequelae. The management of ICH is usually supportive treatment in the neuro-intensive care setting, while the body humors deal with the hematoma. Treatment of the hematoma is usually expectant management unless there is neurological deterioration caused by mass effect from the hemorrhage. Some minimally invasive techniques have been explored for lysing and evacuating the hematoma, but none of them have gained a stronghold in the routine clinical management of this condition. Studies mainly in animal (rodent and porcine) ICH models have shown the role of bound and unbound iron in causing neurotoxicity following an ICH. There is currently no noninvasive method for assessing iron levels in the cerebral tissue following ICH. Our study intends to explore the role of magnetic resonance imaging (MRI) in establishing iron levels in cerebral tissue at the periphery of the hematoma following an ICH. Initially, an MRI phantom was constructed with varying concentrations of liquid iron preparation in a water bath container. Susceptibility weighted sequences were utilized to scan this phantom to generate T2* signal magnitude measurements corresponding to the iron concentration in the phantom. Encouraged by the reliability of the measurements on the phantom, patients with ICH were then recruited into this experimental study once the inclusion criteria were met. One control and two human subjects had their brains scanned in a 3 T MRI scanner utilizing the same susceptibility weighted sequence. We found that ICH perihematomal brain tissue iron susceptibility signal measurements were 4 times higher than those of the baseline control and normal contralateral brain tissue. Three different baseline measurements (one control and two contralateral normal brain) revealed a level of 0.1 mg/ml of iron concentration in the contralateral brain tissue in the identical anatomical location as the hematoma, typically in the basal ganglia region. T2 * signal measurements in the brain tissue at the periphery of the basal ganglia hematoma at day 7 following hemorrhage revealed iron concentration of 0.4 mg/ml (approximately 4 times the baseline/control) in two human subjects included in the study. These measurements mimic those obtained in published animal ICH model studies.

Intraventricular Injection of Noncellular Cerebrospinal Fluid from Subarachnoid Hemorrhage Patient into Rat Ventricles Leads to Ventricular Enlargement and Periventricular Injury.

Early brain injury and hydrocephalus (HCP) are important mediators of poor outcome in subarachnoid hemorrhage (SAH) patients. We aim to understand the development of HCP and subependymal cellular injury after intraventricular injection of noncellular human SAH cerebrospinal fluid (CSF) into rat ventricles. Two-hundred microliters of noncellular CSF from SAH patients or normal controls were injected into the right lateral ventricle of seven adult male Sprague-Dawley rats. Propidium iodide (PI) was simultaneously injected to detect necrotic cellular death. Rats were then sacrificed 24 h after surgery and the brain specimens were cut and stained for heme oxygenase 1 (HO-1), an oxidative stress marker. We found that the ventricular area at the bregma level in the CSF injection group was significantly larger than that in the control group (p < 0.05). The periventricular tissue in the CSF injection group had significantly more necrotic cell death as well as HO-1 expression as compared with the control group (p < 0.05). In conclusion, injection of SAH patients' CSF into the rat ventricle leads to HCP as well as subependymal injury compared with injection of control CSF.

Aspirin and Clopidogrel Inhibit Aneurysm Healing after HydroCoil Implantation in External Carotid Artery Aneurysm Model.

PURPOSE: To understand whether the use of antiplatelet agents leads to less intra-aneurismal tissue formation following coil implantation in a rat end-pouch external carotid artery (ECA) aneurysm model. METHODS: End-pouch ECA aneurysms were created in adult rats and were then embedded with either platinum or HydroCoils. Rats were treated either with aspirin, clopidogrel, aspirin + clopidogrel, or saline for 2 weeks after coil implantation. At 2 weeks after coil implantation, rats were sacrificed and the aneurysm pouch was removed for histological and immunohistochemical analysis. A blinded single observer calculated the percentage of the organized area and the residual length of elastic lamina within the aneurysm. Student's t-test was used to compare data from image analysis between the different groups. RESULTS: Within the platinum group, the organized tissue area was not affected by antiplatelet administration (aspirin versus saline, P = .83; clopidogrel versus saline, P = .46; aspirin + clopidogrel versus saline, P = .54). For the HydroCoil group, the organized tissue area was significantly reduced (aspirin versus saline, P = .02; clopidogrel versus saline, P = .04; aspirin + clopidogrel versus saline, P = .02) in rats treated with antiplatelet agents; however, no difference (aspirin versus clopidogrel, P = .8; aspirin versus aspirin + clopidogrel, P = .3; clopidogrel versus aspirin + clopidogrel, P = .5) was found among type or combination of antiplatelets administered. HydroCoil-treated aneurysms had a similar number of macrophages compared to the platinum group (P = .3819); however, the HydroCoil group had significant suppression of macrophages in the groups treated with combined antiplatelets (P = .02). CONCLUSION: Following HydroCoil implantation, the area of organized tissue is diminished significantly in a rat end-pouch ECA aneurysm model treated with antiplatelets.

Intra-arterial Stroke Treatment prior to the Stent-Retriever Era: High Mortality and Lack of Volume-Outcome Association.

BACKGROUND: Mechanical thrombectomy for acute large-vessel occlusive stroke is beneficial when performed with stent-retriever devices; however, little is known about real-world experience with intra-arterial treatment (IAT). We aimed to clarify how hospitals influence outcomes for Medicare thrombectomy patients to inform future delivery of effective mechanical thrombectomy treatment. METHODS: This is a retrospective cohort study that includes a Medicare fee-for-service patient population. Patients with a primary stroke discharge (ICD-9-CM 433.x1, 434.x1, 436) were included; billing codes were used to identify patients receiving IAT, intravenous thrombolytics (IVT), or a combination of these treatments. Characteristics of treated patients were summarized using descriptive statistics; long-term mortality was summarized via Kaplan-Meier curves; and multilevel logistic regression models with random hospital-level intercept were built to determine hospital influence on outcome and whether a volume-outcome association existed. RESULTS: A total of 4557 patients received IAT at 544 hospitals. The mean age of IAT patients was 76 years. IAT patients had longer hospital stay (9.7 versus 6.8 days), longer stay in the ICU (5.5 versus 3.3 days), and greater probability of intubation (36.7% versus 9.5%) compared with IVT patients. Ninety-day mortality was 46% IAT versus 26% IVT. Hospitals had little influence on outcomes (intraclass correlation coefficient, <.01). No association between procedural volume and outcomes was identified. CONCLUSIONS: IAT for 2007-2010 was associated with higher patient mortality than recent and prior clinical trials. Treated Medicare patients were considerably older than clinical trial populations. Hospitals had little influence on mortality, and increased hospital volume was not associated with lower mortality. Future real-world experience should monitor these parameters as use of stent retrievers disseminates.