Contrast Injection from an Intermediate Catheter Placed in an Intradural Artery is Associated with Contrast-Induced Encephalopathy following Neurointervention.

BACKGROUND AND PURPOSE: Contrast-induced encephalopathy can result from neurotoxicity of contrast medium in the affected area. The development of intermediate catheters has allowed guidance of catheters to more distal arteries. This study focused on the association between contrast-induced encephalopathy and contrast injection from an intermediate catheter guided into a distal intradural artery during neurointervention for cerebral aneurysms. MATERIALS AND METHODS: We retrospectively reviewed 420 consecutive aneurysms in 396 patients who underwent neurointervention for extracranial aneurysms and unruptured intracranial aneurysms at our institution from February 2012 to January 2023. Patients were divided into a group with contrast-induced encephalopathy and a group without. To identify risk factors for contrast-induced encephalopathy, we compared clinical, anatomic, and procedural factors between groups by multivariate logistic regression analysis and stepwise selection. RESULTS: Among the 396 patients who underwent neurointervention for cerebral aneurysms, 14 (3.5%) developed contrast-induced encephalopathy. Compared with the group without contrast-induced encephalopathy, the group with contrast-induced encephalopathy showed significantly higher rates of patients on hemodialysis, previously treated aneurysms, intradural placement of a catheter for angiography, nonionic contrast medium, and flow-diversion procedures in univariate analyses. Stepwise multivariate logistic regression analysis revealed intradural placement of a catheter for angiography (OR = 40.4; 95% CI, 8.63-189) and previously treated aneurysms (OR = 8.20; 95% CI, 2.26-29.6) as independent predictors of contrast-induced encephalopathy. CONCLUSIONS: Contrast injection from an intradural artery and retreatment of recurrent aneurysms were major risk factors for contrast-induced encephalopathy. Attention should be paid to the location of the intermediate catheter for angiography to avoid developing contrast-induced encephalopathy.

Agreement of intracranial vessel diameters measured on 2D and 3D digital subtraction angiography using an automatic windowing algorithm.

BACKGROUND AND PURPOSE: Precise vessel measurement plays a major role in size selection of stents used for the treatment of intracranial aneurysms and became even more critical after the introduction of flow diverter stents. We assessed agreement between intracranial vessel diameters of aneurysm patients measured on 2D digital subtraction (2D DSA) and 3D volume rendering digital subtraction angiography (3D DSA) images using an automatic windowing algorithm. MATERIALS AND METHODS: Ten patients with intracranial aneurysms were enrolled and 120 measurement points were selected on both 2D and 3D DSA images acquired by a biplane angiographic system. Automatic windowing was applied to the 3D DSA images. Inter-method agreement of vessel measurements on 2D and 3D DSA images was assessed by Bland Altman plots and intraclass correlation coefficients (ICC). Inter- and intra-rater agreement of measurements on 3D DSA images were assessed by ICCs. RESULTS: The mean differences between measurements on 2D and 3D DSA images were 0.14mm for the ICA, and 0.18mm for the ACA and MCA, which is about the size of one 3D DSA image voxel. For ICA measurements, inter-method, inter-rater and intra-rater agreements were good or excellent (consistency and absolute ICC≥0.95). For ACA and MCA measurements, the inter-method, inter-rater and intra-rater agreements were also good or excellent (consistency ICC=0.94, 0.89 and 0.93, absolute ICC=0.83, 0.84 and 0.85 respectively). CONCLUSIONS: Vessel diameters may be measured on 3D DSA images with sufficient reliability for clinical use when applying an automatic windowing algorithm.

Microcatheter Originating Debris during Neuroendovascular Procedures: Mechanism of Dislodgement and Its Prevention.

Embolic material dislodgement from microcatheters can potentially induce subclinical brain damage as evidenced by a delayed enhanced or other type of lesions. Some of the most frequently used microcatheters were investigated in vitro in different setups and combinations with different port insertions and rotating hemostatic valves. It was found that side port application increases injury to the catheter surface and debris dislodgement by conflicting with internal ledges in rotating hemostatic valves. This initial observation suggests the need for measures to remove the produced debris during such procedures.

Delayed Leukoencephalopathy: A Rare Complication after Coiling of Cerebral Aneurysms.

BACKGROUND AND PURPOSE: Delayed leukoencephalopathy is a rare complication that occurs after endovascular coiling of cerebral aneurysms. We aimed to describe a clinical picture of delayed leukoencephalopathy and explore potential associations with procedural characteristics. MATERIALS AND METHODS: We considered endovascular coiling procedures for cerebral aneurysms performed between January 2006 and December 2017 in our institution with follow-up MRIs. We used logistic regression models to estimate the ORs of delayed leukoencephalopathy for each procedural characteristic. RESULTS: We reviewed 1754 endovascular coiling procedures of 1594 aneurysms. Sixteen of 1722 (0.9%) procedures demonstrated delayed leukoencephalopathy on follow-up FLAIR MR imaging examinations after a median period of 71.5 days (interquartile range, 30-101 days) in the form of high-signal changes in the white matter at locations remote from the coil mass. Seven patients had headaches or hemiparesis, and 9 patients were asymptomatic. All imaging-associated changes improved subsequently. We found indications suggesting an association between delayed leukoencephalopathy and the number of microcatheters used per procedure (P = .009), along with indications suggesting that these procedures required larger median volumes of contrast medium (225 versus 175 mL, OR = 5.5, P = .008) as well as a longer median fluoroscopy duration (123.6 versus 99.3 minutes, OR = 3.0, P = .06). Our data did not suggest that delayed leukoencephalopathy was associated with the number of coils (P = .57), microguidewires (P = .35), and guiding systems (P = .57). CONCLUSIONS: Delayed leukoencephalopathy after coiling of cerebral aneurysms may have multiple etiologies such as foreign body emboli, contrast-induced encephalopathy, or hypersensitivity reaction to foreign bodies.

Comparison of hemodynamic parameters that can predict an aneurysmal rupture: 20 patient-specific models experiment.

Hemodynamic analysis of cerebral aneurysms is widely performed to understand the mechanism of aneurysmal rupture. Computational fluid dynamics (CFD) studies have suggested that several hemodynamic parameters are associated with such ruptures. However, a number of factors remain to be addressed to correlate these parameters with aneurysmal ruptures, especially under analytical conditions. Specifically, CFD analysis is often performed with rigid wall models due to computational cost limitations. Here, to evaluate the effects of the deformation of the aneurysmal wall, experimental flow measurement with elastic models under pulsating conditions was conducted using three-dimensional particle image velocimetry (3D PIV). By analyzing 20 patient-specific, elastic, silicone aneurysm models, the hemodynamic parameters of ruptured and unruptured aneurysms were statistically compared to identify the variables that can effectively predict an aneurysmal rupture. Our analyses yielded three parameters (average wall shear stress ratio, in-phase deviation ratio, and pressure difference) which could effectively predict an aneurysmal rupture. These results suggested that measurement of wall shear stress (WSS) at both the aneurysm dome and parent artery is important and that pressure difference can also be a potential indicator of aneurysmal rupture.

Relation Between Cognitive Function and Baseline Concentrations of Hemoglobin in Prefrontal Cortex of Elderly People Measured by Time-Resolved Near-Infrared Spectroscopy.

We evaluated relationship between cognitive function and cerebral blood oxygenation (CBO) of the prefrontal cortex (PFC) at rest in 113 adults (age 72.3 ± 12.0 years). We employed a two channel time-resolved near-infrared spectroscopy (TRS), which allows non-invasive measurements of baseline concentrations of oxyhemoglobin (oxy-Hb), deoxyhemoglobin (deoxy-Hb), total-hemoglobin (t-Hb) (µM) and oxygen saturation (SO2, %) of the bilateral PFC without any tasks. We examined cognitive functions using the Mini-Mental State Examination (MMSE) (range from 0 to 30) and the Touch M which evaluates working memory function semi-automatically on a touchscreen (range from 0 to 100); the mean MMSE and Touch M scores of all subjects were 24.8 ± 4.6 (mean ± SD; range 11-30) and 41.3 ± 22.1 (range 1-100), respectively. Employing Pearson's correlation analysis, we evaluated correlation between the TRS parameters and cognitive function. We found a significant positive correlation between the MMSE scores and SO2 (r = 0.24, p < 0.02). In addition, we observed significant positive correlations between Touch M scores and baseline concentrations of oxy-Hb (r = 0.26, p < 0.02), total-Hb (r = 0.23, p < 0.05), and SO2 (r = 0.23, p < 0.05). TRS allowed us to evaluate the relation between CBO in the PFC at rest and cognitive function.

Geographic Differences in Endovascular Treatment and Retreatment of Cerebral Aneurysms.

BACKGROUND AND PURPOSE: Comparing outcomes between endovascular aneurysm coiling trials can be difficult because of heterogeneity in patients and end points. We sought to understand the impact of geography on aneurysm retreatment in patients enrolled in the Matrix and Platinum Science Trial. MATERIALS AND METHODS: Post hoc analysis was performed on data from the Matrix and Platinum Science trial. Patients were stratified as either North American or international. Baseline patient demographics, comorbidities, aneurysm characteristics, procedural complications, and clinical and angiographic outcomes were compared. RESULTS: We evaluated 407 patients from 28 North American sites and 219 patients from 15 international sites. Patient demographics differed significantly between North American and international sites. Aneurysms were well occluded postprocedure more often at international than North American sites (P < .001). Stents were used significantly more often at North American sites (32.7% [133 of 407]) compared with international sites (10.0% [22 of 219]; P < .001). At 455 days, there was no difference in the proportion of patients alive and free of disability (P = .56) or with residual aneurysm filling (P = .10). Ruptured aneurysms were significantly more likely to have been retreated at North American sites within the first year (P < .001) and at 2 years (P < .001). Among all patients for whom the treating physician believed there to be Raymond 3 aneurysm filling at follow-up, absolute rates of retreatment at international and North American sites were similar by 2-year follow-up. CONCLUSIONS: Data from the Matrix and Platinum Science Trial demonstrate that aneurysm retreatment occurs with different frequency and at different times in different regions of the world. This trend has critical value when interpreting trials reporting short-term outcomes, especially when judgment-based metrics such as retreatment are primary end points that may or may not take place within the defined study follow-up period. Though these variations can be controlled for and balanced within a given randomized trial, such differences in practice patterns must be accounted for in any attempt to compare outcomes between different trials. Despite these differences, endovascular-treated intracranial aneurysms around the world have similar clinical outcomes.

Highly sensitive fluorescence detection of metastatic lymph nodes of gastric cancer with photo-oxidation of protoporphyrin IX.

BACKGROUND: The establishment of a precise and rapid method to detect metastatic lymph nodes (LNs) is essential to perform less invasive surgery with reduced gastrectomy along with reduced lymph node dissection. We herein describe a novel imaging strategy to detect 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX (PpIX) fluorescence in excised LNs specifically with reduced effects of tissue autofluorescence based on photo-oxidation of PpIX. We applied the method in a clinical setting, and evaluated its feasibility. METHODS: To reduce the unfavorable effect of autofluorescence, we focused on photo-oxidation of PpIX: Following light irradiation, PpIX changes into another substance, photo-protoporphyrin, via an oxidative process, which has a different spectral peak, at 675 nm, whereas PpIX has its spectral peak at 635 nm. Based on the unique spectral alteration, fluorescence spectral imaging before and after light irradiation and subsequent originally-developed image processing was performed. Following in vitro study, we applied this method to a total of 662 excised LNs obtained from 30 gastric cancer patients administered 5-ALA preoperatively. RESULTS: Specific visualization of PpIX was achieved in in vitro study. The method allowed highly sensitive detection of metastatic LNs, with sensitivity of 91.9% and specificity of 90.8% in the in vivo clinical trial. Receiver operating characteristic analysis indicated high diagnostic accuracy, with the area under the curve of 0.926. CONCLUSIONS: We established a highly sensitive and specific 5-ALA-induced fluorescence imaging method applicable in clinical settings. The novel method has a potential to become a useful tool for intraoperative rapid diagnosis of LN metastasis.

L-Arginine ethylester enhances in vitro amplification of PrP(Sc) in macaques with atypical L-type bovine spongiform encephalopathy and enables presymptomatic detection of PrP(Sc) in the bodily fluids.

Protease-resistant, misfolded isoforms (PrP(Sc)) of a normal cellular prion protein (PrP(C)) in the bodily fluids, including blood, urine, and saliva, are expected to be useful diagnostic markers of prion diseases, and nonhuman primate models are suited for performing valid diagnostic tests for human Creutzfeldt-Jakob disease (CJD). We developed an effective amplification method for PrP(Sc) derived from macaques infected with the atypical L-type bovine spongiform encephalopathy (L-BSE) prion by using mouse brain homogenate as a substrate in the presence of polyanions and L-arginine ethylester. This method was highly sensitive and detected PrP(Sc) in infected brain homogenate diluted up to 10(10) by sequential amplification. This method in combination with PrP(Sc) precipitation by sodium phosphotungstic acid is capable of amplifying very small amounts of PrP(Sc) contained in the cerebrospinal fluid (CSF), saliva, urine, and plasma of macaques that have been intracerebrally inoculated with the L-BSE prion. Furthermore, PrP(Sc) was detectable in the saliva or urine samples as well as CSF samples obtained at the preclinical phases of the disease. Thus, our novel method may be useful for furthering the understanding of bodily fluid leakage of PrP(Sc) in nonhuman primate models.

Hand-assisted laparoscopic transhiatal esophagectomy with a systematic procedure for en bloc infracarinal lymph node dissection.

Laparoscopic transhiatal esophagectomy is a minimally invasive approach for esophageal cancer. However, a transhiatal procedure has not yet been established for en bloc mediastinal dissection. The purpose of this study was to present our novel procedure, hand-assisted laparoscopic transhiatal esophagectomy, with a systematic procedure for en bloc mediastinal dissection. The perioperative outcomes of patients who underwent this procedure were retrospectively analyzed. Transhiatal subtotal mobilization of the thoracic esophagus with en bloc lymph node dissection distally from the carina was performed according to a standardized procedure using a hand-assisted laparoscopic technique, in which the operator used a long sealing device under appropriate expansion of the operative field by hand assistance and long retractors. The thoracoscopic procedure was performed for upper mediastinal dissection following esophageal resection and retrosternal stomach roll reconstruction, and was avoided based on the nodal status and operative risk. A total of 57 patients underwent surgery between January 2012 and June 2013, and the transthoracic procedure was performed on 34 of these patients. In groups with and without the transthoracic procedure, total operation times were 370 and 216 minutes, blood losses were 238 and 139 mL, and the numbers of retrieved nodes were 39 and 24, respectively. R0 resection rates were similar between the groups. The incidence of recurrent laryngeal nerve palsy was significantly higher in the group with the transthoracic procedure, whereas no significant differences were observed in that of pneumonia between these groups. The hand-assisted laparoscopic transhiatal method, which is characterized by a systematic procedure for en bloc mediastinal dissection supported by hand and long device use, was safe and feasible for minimally invasive esophagectomy.

The impact of deformation of an aneurysm model under pulsatile flow on hemodynamic analysis.

Hemodynamic analysis of cerebral aneurysms has been widely carried out to clarify the mechanisms of their growth and rupture. In several cases, patient-specific aneurysm models made of transparent polymers have been used. Even though periodic changes in aneurysms due to the pulsation of blood flow could be important, the deformation of the model geometry and its effect on hemodynamic evaluation has not been fully investigated. In addition, the fabrication accuracy of aneurysm models has not been evaluated even though it may affect the hemodynamic parameters to be analyzed. In this study, the fabrication accuracy of a silicone aneurysm model was investigated. Additionally, the deformation of the model under pulsatile flow as well as its correlation with flow behavior was evaluated. Consequently, a fabrication method for an aneurysm model with high accuracy was established and the importance of the wall thickness of the model was also specified.

Can sliding-window correlations reveal dynamic functional connectivity in resting-state fMRI?

During the last several years, the focus of research on resting-state functional magnetic resonance imaging (fMRI) has shifted from the analysis of functional connectivity averaged over the duration of scanning sessions to the analysis of changes of functional connectivity within sessions. Although several studies have reported the presence of dynamic functional connectivity (dFC), statistical assessment of the results is not always carried out in a sound way and, in some studies, is even omitted. In this study, we explain why appropriate statistical tests are needed to detect dFC, we describe how they can be carried out and how to assess the performance of dFC measures, and we illustrate the methodology using spontaneous blood-oxygen level-dependent (BOLD) fMRI recordings of macaque monkeys under general anesthesia and in human subjects under resting-state conditions. We mainly focus on sliding-window correlations since these are most widely used in assessing dFC, but also consider a recently proposed non-linear measure. The simulations and methodology, however, are general and can be applied to any measure. The results are twofold. First, through simulations, we show that in typical resting-state sessions of 10 min, it is almost impossible to detect dFC using sliding-window correlations. This prediction is validated by both the macaque and the human data: in none of the individual recording sessions was evidence for dFC found. Second, detection power can be considerably increased by session- or subject-averaging of the measures. In doing so, we found that most of the functional connections are in fact dynamic. With this study, we hope to raise awareness of the statistical pitfalls in the assessment of dFC and how they can be avoided by using appropriate statistical methods.

High-Resolution C-Arm CT and Metal Artifact Reduction Software: A Novel Imaging Modality for Analyzing Aneurysms Treated with Stent-Assisted Coil Embolization.

BACKGROUND AND PURPOSE: Combination of high-resolution C-arm CT and novel metal artifact reduction software may contribute to the assessment of aneurysms treated with stent-assisted coil embolization. This study aimed to evaluate the efficacy of a novel Metal Artifact Reduction prototype software combined with the currently available high spatial-resolution C-arm CT prototype implementation by using an experimental aneurysm model treated with stent-assisted coil embolization. MATERIALS AND METHODS: Eight experimental aneurysms were created in 6 swine. Coil embolization of each aneurysm was performed by using a stent-assisted technique. High-resolution C-arm CT with intra-arterial contrast injection was performed immediately after the treatment. The obtained images were processed with Metal Artifact Reduction. Five neurointerventional specialists reviewed the image quality before and after Metal Artifact Reduction. Observational and quantitative analyses (via image analysis software) were performed. RESULTS: Every aneurysm was successfully created and treated with stent-assisted coil embolization. Before Metal Artifact Reduction, coil loops protruding through the stent lumen were not visualized due to the prominent metal artifacts produced by the coils. These became visible after Metal Artifact Reduction processing. Contrast filling in the residual aneurysm was also visualized after Metal Artifact Reduction in every aneurysm. Both the observational (P < .0001) and quantitative (P < .001) analyses showed significant reduction of the metal artifacts after application of the Metal Artifact Reduction prototype software. CONCLUSIONS: The combination of high-resolution C-arm CT and Metal Artifact Reduction enables differentiation of the coil mass, stent, and contrast material on the same image by significantly reducing the metal artifacts produced by the platinum coils. This novel image technique may improve the assessment of aneurysms treated with stent-assisted coil embolization.

Construction and molecular characterization of a T-cell receptor-like antibody and CAR-T cells specific for minor histocompatibility antigen HA-1H.

The genetic transfer of T-cell receptors (TCRs) directed toward target antigens into T lymphocytes has been used to generate antitumor T cells efficiently without the need for the in vitro induction and expansion of T cells with cognate specificity. Alternatively, T cells have been gene-modified with a TCR-like antibody or chimeric antigen receptor (CAR). We show that immunization of HLA-A2 transgenic mice with tetramerized recombinant HLA-A2 incorporating HA-1 H minor histocompatibility antigen (mHag) peptides and ß2-microglobulin (HA-1 H/HLA-A2) generate highly specific antibodies. One single-chain variable region moiety (scFv) antibody, #131, demonstrated high affinity (KD=14.9 nM) for the HA-1 H/HLA-A2 complex. Primary human T cells transduced with #131 scFV coupled to CD28 transmembrane and CD3ζ domains were stained with HA-1 H/HLA-A2 tetramers slightly more intensely than a cytotoxic T lymphocyte (CTL) clone specific for endogenously HLA-A2- and HA-1 H-positive cells. Although #131 scFv CAR-T cells required >100-fold higher antigen density to exert cytotoxicity compared with the cognate CTL clone, they could produce inflammatory cytokines against cells expressing HLA-A2 and HA-1 H transgenes. These data implicate that T cells with high-affinity antigen receptors reduce the ability to lyse targets with low-density peptide/MHC complexes (~100 per cell), while they could respond at cytokine production level.

Natural course of dissecting vertebrobasilar artery aneurysms without stroke.

BACKGROUND AND PURPOSE: The natural history and therapeutic management of dissecting vertebrobasilar aneurysms without ischemic or hemorrhagic stroke (nonstroke dissecting vertebrobasilar aneurysms) are not well-established. We conservatively followed patients with nonstroke dissecting vertebrobasilar aneurysms and evaluated the factors related to clinical and morphologic deterioration. MATERIALS AND METHODS: One hundred thirteen patients were enrolled and divided by clinical presentation at diagnosis: asymptomatic (group 1, n = 52), pain only (group 2, n = 56), and mass effect (group 3, n = 5). Patients were conservatively managed without intervention and antithrombotic therapy. Clinical outcomes and morphologic changes were analyzed. RESULTS: A total of 113 patients who were diagnosed with nonstroke dissecting vertebrobasilar aneurysm had a mean follow-up of 2.9 years (range, 27 days to 8 years). Throughout that period, 1 patient in group 1 (1.9%) and 1 patient in group 2 (1.8%) showed clinical deterioration due to mass effect, and 1 patient in group 3 (20%) developed ischemic stroke followed by subarachnoid hemorrhage. Most patients (97.3%) were clinically unchanged. Three patients who had clinical deterioration showed aneurysm enlargement (P < .001). Aneurysms remained morphologically unchanged in 91 patients (80.5%). Aneurysm enlargement was seen in 5 patients (4.4%); risk of enlargement was significantly associated with either maximum diameter (hazard ratio = 1.30; 95% CI, 1.11-11.52; P = .001) or aneurysm ≥10 mm (hazard ratio = 18.0; 95% CI, 1.95-167; P = .011). CONCLUSIONS: The natural course of these lesions suggests that acute intervention is not always required and close follow-up without antithrombotic therapy is reasonable. Patients with symptoms due to mass effect or aneurysms of >10 mm may require treatment.