Fellows' Journal Club: Contrast Extravasation on CT Angiography Predicts Hematoma Expansion and Mortality in Acute Traumatic Subdural Hemorrhage

BACKGROUND AND PURPOSE:The presence of active contrast extravasation at CTA predicts hematoma expansion and in-hospital mortality in patients with nontraumatic intracerebral hemorrhage. This study aims to determine the frequency and predictive value of the contrast extravasation in patients with aSDH.MATERIALS AND METHODS:We retrospectively reviewed 157 consecutive patients who presented to our emergency department over a 9-year period with aSDH and underwent CTA at admission and a follow-up NCCT within 48 hours. Two experienced readers, blinded to clinical data, reviewed the CTAs to assess for the presence of contrast extravasation. Medical records were reviewed for baseline clinical characteristics and in-hospital mortality. aSDH maximum width in the axial plane was measured on both baseline and follow-up NCCTs, with hematoma expansion defined as >20% increase from baseline.RESULTS:Active contrast extravasation was identified in 30 of 199 discrete aSDHs (15.1%), with excellent interobserver agreement (κ = 0.80; 95% CI, 0.7–0.9). The presence of contrast extravasation indicated a significantly increased risk of hematoma expansion (odds ratio, 4.5; 95% CI, 2.0–10.1; P = .0001) and in-hospital mortality (odds ratio, 7.6; 95% CI, 2.6–22.3; P = 0.0004). In a multivariate analysis controlled for standard risk factors, the presence of contrast extravasation was an independent predictor of aSDH expansion (P = .001) and in-hospital mortality (P = .0003).CONCLUSIONS:Contrast extravasation stratifies patients with aSDH into those at high risk and those at low risk of hematoma expansion and in-hospital mortality. This distinction could affect patient treatment, clinical trial selection, and possible surgical intervention.

Acute traumatic subdural hemorrhage carries a mortality rate of 68% in patients who are in a coma at the time of presentation.^1–4 The incidence of aSDH is approximately 21% in patients with severe TBI⁴ and decreases to 11% in patients with mild and moderate TBI.⁵ Mortality secondary to aSDH has been related to initial hematoma size, the presence of additional brain injury, midline shift, comatose state, and delay in hematoma evacuation >2 hours after arrival to the emergency department.^6,7 The decision to undertake surgical intervention versus expectant management of aSDH is based on hematoma size, the presence of midline shift, admission GCS score, and hematoma growth.⁸ Early hematoma evacuation (<4 hours) has been shown to improve intracranial pressure and therefore brain perfusion, with a decrease in mortality compared with delayed surgical intervention in comatose patients with severe TBI.⁴ Although a significant proportion of patients are treated nonoperatively (noncomatose patients and comatose patients with aSDH <10 mm in width and/or <5 mm of midline shift), a subset of these aSDHs will expand, necessitating delayed operative intervention. The strong relationship between mass effect and mortality suggests that hematoma expansion is probably deleterious for brain perfusion and clinical outcome.⁹ However, to date, no reliable predictors of aSDHs expansion in the initial 48 hours have been identified. Identifying such a predictor may be helpful in the clinical decision to triage patients to early surgical intervention versus expectant management.Prior studies have found that the presence of active contrast extravasation at CTA, defined as the spot sign, is a powerful predictor of hematoma expansion and in-hospital mortality in patients with primary intracerebral hemorrhage.^9–15 However, to date, no studies have assessed the frequency and predictive value of this important finding in patients with aSDH.In our emergency department, CTA of the head and neck is frequently performed in patients who present with craniocervical trauma to detect vascular injury.^15,16 Subsets of these patients also have an associated aSDH. This study aims to determine the frequency and predictive value for hematoma expansion and in-hospital mortality of the CTA contrast extravasation in patients with aSDH.     

Transcranial Duplex Sonography Predicts Outcome following an Intracerebral Hemorrhage

BACKGROUND AND PURPOSE:Several radiologic features such as hematoma volume are related to poor outcome following an intracerebral hemorrhage and can be measured with transcranial duplex sonography. We sought to determine the prognostic value of transcranial duplex sonography in patients with intracerebral hemorrhage.MATERIALS AND METHODS:We conducted a prospective study of patients diagnosed with spontaneous intracerebral hemorrhage. Transcranial duplex sonography examinations were performed within 2 hours of baseline CT, and we recorded the following variables: hematoma volume, midline shift, third ventricle and lateral ventricle diameters, and the pulsatility index in both MCAs. We correlated these data with the CT scans and assessed the prognostic value of the transcranial duplex sonography measurements. We assessed early neurologic deterioration during hospitalization and mortality at 1-month follow-up.RESULTS:We included 35 patients with a mean age of 72.2 ± 12.8 years. Median baseline hematoma volume was 9.85 mL (interquartile range, 2.74–68.29 mL). We found good agreement and excellent correlation between transcranial duplex sonography and CT when measuring hematoma volume (r = 0.791; P < .001) and midline shift (r = 0.827; P < .001). The logistic regression analysis with transcranial duplex sonography measurements showed that hematoma volume was an independent predictor of early neurologic deterioration (OR, 1.078; 95% CI, 1.023–1.135) and mortality (OR, 1.089; 95% CI, 1.020–1.160). A second regression analysis with CT variables also demonstrated that hematoma volume was associated with early neurologic deterioration and mortality. When we compared the rating operation curves of both models, their predictive power was similar.CONCLUSIONS:Transcranial duplex sonography showed an excellent correlation with CT in assessing hematoma volume and midline shift in patients with intracerebral hemorrhage. Hematoma volume measured with transcranial duplex sonography was an independent predictor of poor outcome.

Spontaneous intracerebral hemorrhage (ICH) is a major cause of morbidity and mortality,¹ with half of the events related to case fatality occurring within the first 48 hours.² Thus, identifying variables that contribute to early neurologic deterioration (END) and mortality is of enormous importance. An early estimation of the prognosis is crucial for deciding on a treatment plan. Several neuroimaging prognostic factors include hematoma volume (HV), hematoma enlargement, midline shift (MLS), and intraventricular hemorrhage,^3–9 and CT is the technique most frequently used to assess them. However, in the early stages, it can be difficult to monitor these radiologic features with repeat CT due to the clinical and/or hemodynamic state of the patient and the risk of radiation overexposure.Transcranial duplex sonography (TDS) is a noninvasive technique that provides simultaneous 2D imaging of brain parenchyma and hemodynamic information from the main cerebral arteries. The role of TDS is well-established in the assessment of ischemic stroke, but its usefulness in acute ICH has been reported in only a few studies.^10–15Visualization of acute ICH with TDS is feasible: The ICH can be identified as a hyperechoic mass.^10–12 Additionally, TDS allows the assessment of the third ventricle (IIIV), the lateral ventricles (LVs), MLS, and the presence of intraventricular hemorrhage.^13–16 TDS may have some potential advantages over CT, including the feasibility of performance at the bedside as many times as necessary and regardless of the hemodynamic situation of the patient. Despite a good correlation between TDS and CT having been previously reported,^10–15 the prognostic value of this technique in ICH is yet to be established.The question of whether TDS may reliably measure ICH characteristics and predict END and mortality following ICH has important implications for clinical practice and research. In the current study, we sought to determine the prognostic value of TDS in patients with acute ICH.     

CT Angiography Findings in Carotid Blowout Syndrome and Its Role as a Predictor of 1-Year Survival

BACKGROUND AND PURPOSE:Carotid blowout is a serious late complication of prior treatment of advanced head and neck cancer. We evaluate the efficacy of CTA in the diagnosis of impending carotid blowout syndrome in patients with head and neck cancer, and its capability to predict clinical outcome.MATERIALS AND METHODS:The clinical data of 29 patients with impending carotid blowout who underwent CTA were collected and analyzed. Imaging signs included tissue necrosis, exposed artery, viable perivascular tumor, pseudoaneurysm, and contrast extravasation. DSA was obtained in 20 patients. One-year outcomes were compared based on management.RESULTS:The most common CTA finding was necrosis (94%), followed by exposed artery (73%), viable tumor (67%), pseudoaneurysm (58%), and contrast extravasation (30%). Exposed artery, pseudoaneurysm, and contrast extravasation were the 3 CTA findings related to outcomes. All of the pseudoaneurysm and contrast extravasation cases were associated with an exposed artery. An exposed artery was the most important prognostic predictor and could not be diagnosed on DSA. Patients without the 3 findings on CTA (group 1) had the best survival rate at 1-year follow-up, followed by patients with the 3 findings treated immediately by permanent artery occlusion (group 2). Patients with the 3 findings who had no immediate treatment (group 3) had the worst outcomes (P < .001 in group 1 vs group 3 and group 2 vs group 3; P = .056 group 1 vs group 2).CONCLUSIONS:CTA, with its ability to diagnose an exposed artery compared with DSA, may offer important management and prognostic information in patients with impending carotid blowout.

Carotid blowout syndrome (CBS) is defined as rupture of the carotid artery and its branches and is a serious complication after treatment of advanced head and neck cancer. Potential causes of CBS include radical resection, radiation therapy and radiation necrosis, carotid exposure, wound infection, pharyngocutaneous fistula, and recurrent or persistent carcinoma.¹ The overall incidence of carotid blowout after neck dissection has been reported to be as high as 4.3%, and the risk is increased another 7.6-fold with further radiation therapy.² CBS typically occurs 2–20 years after surgery or radiation therapy,^3,4 and average estimates of cumulative neurologic morbidity and mortality are above 60% and 40%, respectively, in patients with CBS.⁵ CBS can be categorized into 1 of 3 categories: threatened, impending, and acute carotid blowout.¹ Threatened carotid blowout is defined as physical examination or imaging results that suggest inevitable hemorrhage from 1 of the carotid arteries or its branches if no action is taken. Impending carotid blowout (also called sentinel hemorrhage) is defined as transient hemorrhage that resolves spontaneously or with packing or pressure. Acute carotid blowout represents hemorrhage that cannot be controlled by packing or pressure.¹ Surgical management of carotid blowout is usually technically difficult and is associated with high morbidity and mortality rates.^1,2,6,7 After surgical ligation or permanent arterial occlusion (PAO) of the carotid artery, the incidence of immediate or delayed cerebral ischemic complications can be as high as 15%–20%.^7,8–12 The complication rate of a balloon occlusion test before PAO of the carotid artery is reported to be as high as 3.2%, and it may be even higher in fragile postirradiation vessels.¹³ Delayed ischemia after passing the balloon occlusion test is yet another concern.^10,14,15 Stent-graft deployment, with or without coiling, is another endovascular treatment of CBS. Stent-grafting can preserve the affected carotid flow but has a high rate of early and delayed complications.^16–19 No significant difference in short-term outcome between stent-graft deployment and PAO has been reported,²⁰ and long-term results have not been reported.¹⁷CTA has become widely available and is sensitive and specific in the detection of hemorrhagic vascular disorders such as aneurysms, arteriovenous malformations, dural arteriovenous fistulas, and intracranial dissections. Contrast extravasation on CTA predicts hematoma expansion, mortality, and clinical outcome in primary intracerebral hemorrhage.^21–26 To our knowledge, there have been no past reports about the use of CTA in the diagnosis of CBS or as an outcome predictor. The aim of our study was to evaluate the efficacy of CTA in the diagnosis of impending CBS, and its capability to predict clinical outcome after management.     

Age- and Level-Dependence of Fatty Infiltration in Lumbar Paravertebral Muscles of Healthy Volunteers

BACKGROUND AND PURPOSE:Normative age-related decline in paravertebral muscle quality is important for reference to disease and risk identification in patients. We aimed to establish age- and vertebral level–dependence of paravertebral (multifidus and erector spinae) muscle volume and fat content in healthy adult volunteers.MATERIALS AND METHODS:In this prospective study multifidus and erector spinae fat signal fraction and volume at lumbar levels L1–L5 were measured in 80 healthy volunteers (10 women and men per decade, 20–62 years of age) by 2-point Dixon 3T MR imaging. ANOVA with post hoc Bonferroni correction compared fat signal fraction and volume among subgroups. Pearson and Spearman analysis were used for correlations (P < .05).RESULTS:Fat signal fraction was higher in women (17.8% ± 10.7%) than men (14.7% ± 7.8%; P < .001) and increased with age. Multifidus and erector spinae volume was lower in women (565.4 ± 83.8 cm³) than in men (811.6 ± 98.9 cm³; P < .001) and was age-independent. No differences in fat signal fraction were shown between the right and left paravertebral muscles or among the L1, L2, and L3 lumbar levels. The fat signal fraction was highest at L5 (women, 31.9% ± 9.3%; men, 25.7% ± 8.0%; P < .001). The fat signal fraction at L4 correlated best with total lumbar fat signal fraction (women, r = 0.95; men, r = 0.92, P < .001). Total fat signal fraction was higher in the multifidus compared with erector spinae muscles at L1–L4 for both sexes (P < .001).CONCLUSIONS:Lumbar paravertebral muscle fat content increases with aging, independent of volume, in healthy volunteers 20–62 years of age. Women, low lumbar levels, and the multifidus muscle are most affected. Further study examining younger and older subjects and the functional impact of fatty infiltrated paravertebral muscles are warranted.

MR imaging is the criterion standard for evaluating the size and structure of soft-aqueous skeletal muscles.^1,2 While T1WI is commonly used for qualitative assessment of muscle fat infiltration (MFI),^3,4 chemical-shift–based imaging sequences allow quantification,^5–7 which correlates with clinical symptoms^3,8 and histology.^2,9The Dixon technique is a robust chemical-shift imaging application producing water- and fat-only images from dual-echo acquisitions.^10,11 Excellent accuracy for MFI quantification is shown in comparison with T1WI,¹² spectroscopy,⁵ and histology in different animal species.⁹ Accordingly, Dixon MR imaging was used for evaluating muscle fat content in several clinical studies including patients with low back pain (LBP),^5,13 acute-to-chronic whiplash,¹⁴ and neuromuscular disorders.¹⁵Quantification of degeneration (fat infiltration and atrophy) of lumbar paravertebral muscles has attracted interest in understanding their biologic influence on persistent LBP. Atrophy and fat infiltrates are identified in patients^16–21 and following experimentally induced lesions in a porcine model.²² However, human studies describing lumbar MFI report inconsistent findings: An association with LBP was demonstrated in some^18,23–26 but not in others.^13,16One explanation for discrepant findings is the influence of age on muscle composition.^{17,18,27–29} Spinal degeneration is known to occur early and increasingly throughout the life span,³⁰ yet to our knowledge, no study has assessed age-related morphologic changes to lumbar paravertebral muscles in healthy volunteers, which would provide a crucial supplement for future comparative studies.We sought to quantify lumbar paravertebral muscle volume and fat content by 2-point Dixon MR imaging in healthy adult volunteers spanning 4 decades of life, and we aimed to establish an age- and level-dependent reference of lumbar paravertebral muscle volume and fat content as a reflection of natural aging history. We hypothesize greater MFI with age for both sexes and lumbar MFI level–dependence with an increasing craniocaudal trend.     

Different Characteristics of the Corticospinal Tract According to the Cerebral Origin: DTI Study

BACKGROUND AND PURPOSE:Little is known about differences in corticospinal tract fibers according to cerebral origin. Using diffusion tensor tractography, we attempted to investigate the characteristics of the CST according to the cerebral origin in the human brain.MATERIALS AND METHODS:Thirty-six healthy subjects were recruited for this study. A 1.5T Gyroscan Intera system was used for acquisition of DTI. CSTs were reconstructed by selection of fibers passing through seed and target ROIs: seed ROIs, the area of the CST at the pontomedullary junction; target ROIs, the primary motor cortex, the primary somatosensory cortex, the dorsal premotor cortex, and the supplementary motor area.RESULTS:A significant difference in tract volume was observed in each ROI (P < .05): M1 (2373.6, 36.9%), S1 (2037.7, 31.7%), SMA (1588.0, 24.7%), and dPMC (429.8, 6.7%). Regarding fractional anisotropy values, the dPMC or SMA showed higher values than the M1 or S1; however, the opposite occurred in terms of the mean diffusivity value (P < .05). In addition, fractional anisotropy and mean diffusivity values of the dPMC differed from those of the SMA (P < .05); in contrast, no significant difference was observed between the M1 and S1 (P > .05).CONCLUSIONS:Tract volume was found to differ according to cerebral origin and was, in descending order, M1, S1, SMA, and dPMC. In addition, the directionality and diffusivity of CST fibers in the SMA and the dPMC differed from those of the M1 and S1, which showed similar characteristics.

The corticospinal tract is a major neural tract for motor function in the human brain.^1–5 The CST is known be involved mainly in movement execution of distal extremities, particularly fine-motor activities of the hand.^1–5 The CST originates from various cortical areas, such as the secondary motor area, the parietal cortex, and the primary motor cortex. The multiple cerebral origins of the CST appear to be important in terms of multiple functions of CST fibers and motor recovery mechanisms: perilesional reorganization following M1 injury.^6–10 Many previous studies have reported differences in characteristics of CST fibers, in terms of the amount of CST fibers and function, according to the origin of the cerebral cortex.^11–18 Most of these studies have used animal brains because only postmortem histologic studies or microelectrode stimulation studies have been used for research on the human brain.^11,14–17By contrast, diffusion tensor tractography, a technique derived from DTI, allows 3D visualization and estimation of the CST.^19–21 Several diffusion tensor tractography studies have reported the characteristics of the whole CST^22–24; however, little is known about differences in CST fibers according to the cerebral origin.¹⁷In the current study, by using diffusion tensor tractography, we attempted to investigate the characteristics of the CST according to the cerebral origin in the human brain.     

Dual-Energy CT in Enhancing Subdural Effusions that Masquerade as Subdural Hematomas: Diagnosis with Virtual High-Monochromatic (190-keV) Images

BACKGROUND AND PURPOSE:Extravasation of iodinated contrast into subdural space following contrast-enhanced radiographic studies results in hyperdense subdural effusions, which can be mistaken as acute subdural hematomas on follow-up noncontrast head CTs. Our aim was to identify the factors associated with contrast-enhancing subdural effusion, characterize diffusion and washout kinetics of iodine in enhancing subdural effusion, and assess the utility of dual-energy CT in differentiating enhancing subdural effusion from subdural hematoma.MATERIALS AND METHODS:We retrospectively analyzed follow-up head dual-energy CT studies in 423 patients with polytrauma who had undergone contrast-enhanced whole-body CT. Twenty-four patients with enhancing subdural effusion composed the study group, and 24 randomly selected patients with subdural hematoma were enrolled in the comparison group. Postprocessing with syngo.via was performed to determine the diffusion and washout kinetics of iodine. The sensitivity and specificity of dual-energy CT for the diagnosis of enhancing subdural effusion were determined with 120-kV, virtual monochromatic energy (190-keV) and virtual noncontrast images.RESULTS:Patients with enhancing subdural effusion were significantly older (mean, 69 years; 95% CI, 60–78 years; P < .001) and had a higher incidence of intracranial hemorrhage (P = .001). Peak iodine concentration in enhancing subdural effusions was reached within the first 8 hours of contrast administration with a mean of 0.98 mg/mL (95% CI, 0.81–1.13 mg/mL), and complete washout was achieved at 38 hours. For the presence of a hyperdense subdural collection on 120-kV images with a loss of hyperattenuation on 190-keV and virtual noncontrast images, when considered as a true-positive for enhancing subdural effusion, the sensitivity was 100% (95% CI, 85.75%–100%) and the specificity was 91.67% (95% CI, 73%–99%).CONCLUSIONS:Dual-energy CT has a high sensitivity and specificity in differentiating enhancing subdural effusion from subdural hematoma. Hence, dual-energy CT has a potential to obviate follow-up studies.

Diffusion of contrast material into the subdural space following intravascular contrast administration can result in hyperdense enhancing subdural effusions (ESDEs) on follow-up noncontrast head CTs.^1,2 These effusions can be mistaken for subdural hematomas (SDHs).^1,2 Three case reports have previously described ESDEs, all following intra-arterial contrast administration during conventional angiography with resolution documented on short-term follow-up CT examinations.^1,2We have frequently observed ESDEs in our busy level 1 trauma center, where patients usually undergo admission contrast-enhanced whole-body CT followed by serial noncontrast head CTs for documented or suspected traumatic brain injury. Because ESDEs can be mistaken for SDHs, lack of awareness of this entity can potentially result in needless delays in instituting thromboprophylaxis and trigger unnecessary follow-up CT studies. Patients with polytrauma usually require thromboprophylaxis to prevent deep vein thrombosis. A number of authors have posited a mandatory 24- to 72-hour period of documented stability of intracranial bleeds before beginning thromboprophylaxis.^3–6 Hence, early discrimination of SDHs from ESDEs has important clinical implications.On single-energy CT (SECT), the hyperattenuation caused by hemorrhage and contrast medium is difficult to distinguish due to overlapping Hounsfield units (HU).^1,2,7,8 Present recommendations for differentiating SDH from ESDE involve serial follow-up imaging.^1,2 ESDEs shows rapid washout of contrast, hence decreasing hyperattenuation, while SDH retains hyperattenuation from blood for 2–3 weeks.^1,2,9 Dual-energy CT (DECT) can potentially obviate follow-up scans by differentiating iodine from hemorrhage.^7,10,11 Iodine overlay maps and virtual noncontrast (VNC) images can discriminate contrast and hemorrhage with a high degree of accuracy.¹¹ If VNC images can be used to reliably identify hematoma, even in the presence of iodine, differentiation between ESDEs and SDHs can be a simple and straightforward task. The utility of DECT in diagnosing ESDE was recently demonstrated in a case in which a subdural hyperdense collection that developed after endovascular treatment of an intracranial aneurysm was hyperdense on iodine-overlay images and hypodense on VNC images.¹² This evidence suggests that DECT may play a vital role in providing an early definitive diagnosis without the need for follow-up CT studies to document resolution of ESDEs.The purpose of this study was to identify the factors associated with ESDE, characterize the diffusion and washout kinetics of iodine in ESDE, and assess the utility of DECT in differentiating ESDE from SDH.     

The Safety of Intra-arterial Tirofiban during Endovascular Therapy after Intravenous Thrombolysis

BACKGROUND AND PURPOSE:The safety and efficacy of tirofiban during endovascular therapy in patients undergoing intravenous thrombolysis with recombinant IV tPA remain unclear. This study aimed to investigate the safety and efficacy of intra-arterial tirofiban use during endovascular therapy in patients treated with IV tPA.MATERIALS AND METHODS:Using a multicenter registry, we enrolled patients with acute ischemic stroke who underwent endovascular therapy. Safety outcomes included postprocedural parenchymal hematoma type 2 and/or thick subarachnoid hemorrhage, intraventricular hemorrhage, and 3-month mortality. Efficacy outcomes included the successful reperfusion rate, postprocedural reocclusion, and good outcomes at 3 months (mRS scores of 0–2). The tirofiban effect on the outcomes was evaluated using a multivariable analysis while adjusting for potential confounders.RESULTS:Among enrolled patients, we identified 314 patients with stroke (279 and 35 patients in the no tirofiban and tirofiban groups, respectively) due to an intracranial artery occlusion who underwent endovascular therapy with intravenous thrombolysis. A multivariable analysis revealed no association of intra-arterial tirofiban with postprocedural parenchymal hematoma type and/or thick subarachnoid hemorrhage (adjusted OR, 1.07; 95% CI, 0.20–4.10; P = .918), intraventricular hemorrhage (adjusted OR, 0.43; 95% CI, 0.02–2.85; P = .467), and 3-month mortality (adjusted OR, 0.38; 95% CI, 0.04–1.87; P = .299). Intra-arterial tirofiban was not associated with good outcome (adjusted OR, 2.22; 95% CI, 0.89 –6.12; P = .099).CONCLUSIONS:Using intra-arterial tirofiban during endovascular therapy after IV tPA could be safe.

Given the positive findings of randomized controlled trials of endovascular therapy (EVT) with newer devices,^1-5 EVT has become a standard therapy for anterior circulation ischemic stroke.^2,4 Although it remains unclear whether EVT combined with intravenous thrombolysis (IVT) with tPA is better than EVT alone, the American Stroke Association/American Heart Association guidelines recommends IVT for eligible patients with large-vessel occlusion (LVO).⁶IV tPA improves outcomes in patients with acute ischemic stroke.⁷ However, given that IV tPA increases the risk of intracranial hemorrhage, it limits additional procedural techniques during EVT. A large pivotal study on EVT reported that 29% of patients lacked successful reperfusion (modified TICI [mTICI] ≧ 2b).⁸ Additionally, during EVT, endothelial damage can occur with resulting platelet activation, which causes reocclusion.⁹ This often requires rescue treatment, including balloon angioplasty, stent placement, or adjuvant thrombolytic infusion. Although antiplatelet agents or thrombolytic infusion has benefits in cases involving stent deployment or ongoing thrombus formation, these treatments may increase the risk of bleeding complications.Tirofiban is the most commonly used rescue thrombolytic.¹⁰ However, its safety and efficacy in EVT among patients with acute ischemic stroke remain unclear.^11-17 Additionally, although studies of EVT have reported that 83% of patients were treated with IV tPA before EVT,⁸ there is no evidence regarding the use of tirofiban during EVT in patients treated with IV tPA.Therefore, this study aimed to investigate the safety and efficacy of intra-arterial (IA) tirofiban during EVT in patients treated with IV tPA.     

Effects of MRI Protocol Parameters,Preload Injection Dose,Fractionation Strategies,and Leakage Correction Algorithms on the Fidelity of Dynamic-Susceptibility Contrast MRI Estimates of Relative Cerebral Blood Volume in Gliomas

BACKGROUND AND PURPOSE:DSC perfusion MR imaging assumes that the contrast agent remains intravascular; thus, disruptions in the blood-brain barrier common in brain tumors can lead to errors in the estimation of relative CBV. Acquisition strategies, including the choice of flip angle, TE, TR, and preload dose and incubation time, along with post hoc leakage-correction algorithms, have been proposed as means for combating these leakage effects. In the current study, we used DSC-MR imaging simulations to examine the influence of these various acquisition parameters and leakage-correction strategies on the faithful estimation of CBV.MATERIALS AND METHODS:DSC-MR imaging simulations were performed in 250 tumors with perfusion characteristics randomly generated from the distributions of real tumor population data, and comparison of leakage-corrected CBV was performed with a theoretic curve with no permeability. Optimal strategies were determined by protocol with the lowest mean error.RESULTS:The following acquisition strategies (flip angle/TE/TR and contrast dose allocation for preload and bolus) produced high CBV fidelity, as measured by the percentage difference from a hypothetic tumor with no leakage: 1) 35°/35 ms/1.5 seconds with no preload and full dose for DSC-MR imaging, 2) 35°/25 ms/1.5 seconds with ¼ dose preload and ¾ dose bolus, 3) 60°/35 ms/2.0 seconds with ½ dose preload and ½ dose bolus, and 4) 60°/35 ms/1.0 second with 1 dose preload and 1 dose bolus.CONCLUSIONS:Results suggest that a variety of strategies can yield similarly high fidelity in CBV estimation, namely those that balance T1- and T2*-relaxation effects due to contrast agent extravasation.

DSC-MR imaging is a PWI technique based on the indicator-dilution theory,¹ which uses the first pass of a paramagnetic contrast agent to estimate cerebrovascular parameters, including relative CBV (rCBV) and CBF.^2,3 A primary clinical application for rCBV includes the evaluation of brain tumor vascularity and angiogenesis; however, neovascularity within neoplasms tends to have elevated vascular permeability, resulting in contrast agent leakage into the extravascular extracellular space (EES) and violation of assumptions made by the indicator-dilution theory. These “leakage effects,” which can be either T1-weighted, which would cause underestimation of the rCBV, or T2*-weighted, which would cause overestimation of the rCBV, greatly depend on the acquisition strategy and protocol used for DSC-MR imaging signal acquisition.⁴ To address these problems, strategies have been proposed for reducing the influence of contrast agent leakage, many focusing on T1-weighted artifact reduction, including use of low flip angles,⁵ dual-echo acquisitions,^6–8 preload administration,⁹ and/or postprocessing leakage-correction algorithms.^10–13Previous studies have used a combination of these strategies to reduce extravasation-induced error of CBV estimates; however, these approaches have primarily been evaluated empirically. The goal of this study was to systematically evaluate, with simulation, the effects of various leakage-correction strategies on the fidelity of CBV estimation using simulated DSC-MR imaging data derived from the convolution theory¹⁴ and recent developments by Quarles et al.¹⁵ We hypothesized that this approach could provide insight into the interaction of pulse sequence parameters, preload dosing, and leakage-correction algorithms that are not readily determined experimentally.     

Hyperintense Basilar Artery on FLAIR MR Imaging: Diagnostic Accuracy and Clinical Impact in Patients with Acute Brain Stem Stroke

BACKGROUND AND PURPOSE:FLAIR-hyperintense vessels are known to be a sign of sluggish collateral blood flow in hemispheric vessel occlusion. Additionally, they seem to have a prognostic implication. The aim of the current study was to evaluate the hyperintense configuration of the basilar artery (FLAIR-hyperintense basilar artery) as a marker of basilar artery occlusion and as a predictor of patient outcome.MATERIALS AND METHODS:We retrospectively identified 20 patients with basilar artery occlusion who initially underwent MR imaging with subsequent DSA. The diagnostic accuracy of the FLAIR-hyperintense basilar artery sign was tested by 4 independent readers in a case-control design, and the relation among FLAIR-hyperintense basilar artery and DWI posterior circulation–ASPECTS, patient outcome, and patient survival was evaluated. To grade the extent of the FLAIR-hyperintense basilar artery sign, we generated a score by counting the number of sections from the basilar tip to the foramen magnum in which a hyperintense signal in the vessel lumen was present multiplied by the section thickness.RESULTS:The FLAIR-hyperintense basilar artery sign showed moderate sensitivity (65%–95%) but very good specificity (95%–100%) and accuracy (85%–93%) for the detection of basilar artery occlusion. Substantial or excellent inter-reader agreement was observed (Cohen κ, 0.64–0.85). The FLAIR-hyperintense basilar artery inversely correlated with the posterior circulation–ASPECTS (r = −0.67, P = .01). Higher FLAIR-hyperintense basilar artery scores were associated with patient death (28.3 ± 13.7 versus 13.4 ± 11.1, P < .05).CONCLUSIONS:The FLAIR-hyperintense basilar artery sign proved to be a valuable marker of vessel occlusion and may substantially support the diagnosis of basilar artery occlusion. The established FLAIR-hyperintense basilar artery score may be helpful for the prediction of individual patient survival.

FLAIR-hyperintense vessels (FHVs) are frequently observed in the M2-to-M4 segments of patients with acute ischemic stroke of the anterior circulation. They can be an indicator of occlusion,^1,2 reversible constriction,³ or stenosis^4–6 of intra- and extracranial arteries, and they are identified as the absence of the typical “flow void” in the tortuous sulcal arteries on the cerebral surface.^2,7 It is hypothesized that the FHV sign is caused mainly by sluggish, slow blood flow and also by clot signal intensity, the latter as an effect of oxyhemoglobin.^8,9At the beginning, the FHV sign was mainly proposed as a very sensitive marker of vessel occlusion and of flow impairment in MCA stroke.^8,10–14 Publications dealing with its prognostic significance were rare^8,15 until Lee et al,¹ in 2009, observed a relation between the extent of the FHV and the amount of diffusion-perfusion mismatch in patients with MCA occlusions. They suggested that the FHV is an indicator of collateral flow besides its proved sensitivity for mere blood flow alterations. Since then, there have been several original studies^{3,5,7,16–22} and 1 review² addressing the potential role of the FHV sign as an imaging biomarker of collateral circulation and as a predictor of patient outcome. Although some patients with basilar artery occlusion (BAO) in the low single-digit range were included in a few studies dealing with the diagnostic significance of the FHV sign,^10,12,14 the focus of these investigations has been on patients with MCA stroke. To date, neither the diagnostic nor the prognostic value of the FLAIR-hyperintense basilar artery (FHBA) sign has been investigated in a dedicated study, to our knowledge.     

T1 Signal Measurements in Pediatric Brain: Findings after Multiple Exposures to Gadobenate Dimeglumine for Imaging of Nonneurologic Disease

BACKGROUND AND PURPOSE:Signal intensity increases possibly suggestive of gadolinium retention have recently been reported on unenhanced T1-weighted images of the pediatric brain following multiple exposures to gadolinium-based MR contrast agents. Our aim was to determine whether T1 signal changes suggestive of gadolinium deposition occur in the brains of pediatric nonneurologic patients after multiple exposures to gadobenate dimeglumine.MATERIALS AND METHODS:Thirty-four nonneurologic patients (group 1; 17 males/17 females; mean age, 7.18 years) who received between 5 and 15 injections (mean, 7.8 injections) of 0.05 mmol/kg of gadobenate during a mean of 2.24 years were compared with 24 control patients (group 2; 16 males/8 females; mean age, 8.78 years) who had never received gadolinium-based contrast agents. Exposure to gadobenate was for diagnosis and therapy monitoring. Five blinded readers independently determined the signal intensity at ROIs in the dentate nucleus, globus pallidus, pons, and thalamus on unenhanced T1-weighted spin-echo images from both groups. Unpaired t tests were used to compare signal-intensity values and dentate nucleus–pons and globus pallidus–thalamus signal-intensity ratios between groups 1 and 2.RESULTS:Mean signal-intensity values in the dentate nucleus, globus pallidus, pons, and thalamus of gadobenate-exposed patients ranged from 366.4 to 389.2, 360.5 to 392.9, 370.5 to 374.9, and 356.9 to 371.0, respectively. Corresponding values in gadolinium-based contrast agent–naïve subjects were not significantly different (P > .05). Similarly, no significant differences were noted by any reader for comparisons of the dentate nucleus–pons signal-intensity ratios. One reader noted a difference in the mean globus pallidus–thalamus signal-intensity ratios (1.06 ± 0.006 versus 1.02 ± 0.009, P = .002), but this reflected nonsignificantly higher T1 signal in the thalamus of control subjects. The number of exposures and the interval between the first and last exposures did not influence signal-intensity values.CONCLUSIONS:Signal-intensity increases potentially indicative of gadolinium deposition are not seen in pediatric nonneurologic patients after multiple exposures to low-dose gadobenate.

Recent reports have detailed high signal intensity (SI) in certain brain areas (primarily the dentate nucleus [DN] and globus pallidus [GP]) on unenhanced T1-weighted images following multiple exposures to gadolinium-based contrast agents (GBCAs).^1–20 Many of these reports have focused on apparent differences between macrocyclic and open-chain “linear” GBCAs,^4–13 invariably associating progressive T1 hyperintensity with multiple exposures to linear GBCAs and concluding that observed T1 signal reflects the lower stability of these agents and thus a greater propensity for gadolinium (Gd) release and, subsequently, deposition in the brain. Among the more recent reports are several that describe retrospective assessments in pediatric patients.^15–19 Although each patient evaluated received just 1 specific linear GBCA (gadopentetate dimeglumine; Magnevist; Bayer HealthCare, Wayne, New Jersey), the study-based recommendations in each case were to consider carefully the use of all linear agents in pediatric subjects.Gadobenate dimeglumine (MultiHance; Bracco Diagnostics, Monroe, New Jersey) is an ionic open-chain, linear GBCA that differs fundamentally from gadopentetate and other extracellular GBCAs in having an aromatic substituent on the chelating molecule.²¹ Unique properties conferred by this substituent include increased R1-relaxivity,²² which permits the acquisition of diagnostically valid images with a reduced dose,²³ and liver-specificity, which permits gadobenate use for hepatobiliary-phase liver applications.²⁴ An additional benefit is increased molecular stability compared with gadopentetate, other linear agents, and certain macrocyclic agents.²⁵ Studies that have evaluated brain T1 signal intensities after multiple exposures to gadobenate have yielded conflicting results with one report demonstrating T1 signal increases, albeit to a lesser extent than with gadopentetate,¹⁰ and others demonstrating no direct changes.^11,12We aimed to determine whether multiple exposures to low-dose gadobenate for nonneurologic pathology results in T1 signal changes in the DN and GP of pediatric patients relative to that in age- and weight-matched GBCA-naïve control subjects.     

Endovascular Treatment of Ruptured Blister-Like Aneurysms: A Systematic Review and Meta-Analysis with Focus on Deconstructive versus Reconstructive and Flow-Diverter Treatments

BACKGROUND AND PURPOSE:Various endovascular techniques have been applied to treat blister-like aneurysms. We performed a systematic review to evaluate endovascular treatment for ruptured blister-like aneurysms.MATERIALS AND METHODS:We performed a comprehensive literature search and subgroup analyses to compare deconstructive versus reconstructive techniques and flow diversion versus other reconstructive options.RESULTS:Thirty-one studies with 265 procedures for ruptured blister-like aneurysms were included. Endovascular treatment was associated with a 72.8% (95% CI, 64.2%–81.5%) mid- to long-term occlusion rate and a 19.3% (95% CI, 13.6%–25.1%) retreatment rate. Mid- to long-term neurologic outcome was good in 76.2% (95% CI, 68.9%–8.4%) of patients. Two hundred forty procedures (90.6%) were reconstructive techniques (coiling, stent-assisted coiling, overlapped stent placement, flow diversion) and 25 treatments (9.4%) were deconstructive. Deconstructive techniques had higher rates of initial complete occlusion than reconstructive techniques (77.3% versus 33.0%, P = .0003) but a higher risk for perioperative stroke (29.1% versus 5.0%, P = .04). There was no difference in good mid- to long-term neurologic outcome between groups, with 76.2% for the reconstructive group versus 79.9% for the deconstructive group (P = .30). Of 240 reconstructive procedures, 62 (25.8%) involved flow-diverter stents, with higher rates of mid- to long-term complete occlusion than other reconstructive techniques (90.8% versus 67.9%, P = .03) and a lower rate of retreatment (6.6% versus 30.7%, P < .0001).CONCLUSIONS:Endovascular treatment of ruptured blister-like aneurysms is associated with high rates of complete occlusion and good mid- to long-term neurologic outcomes in most patients. Deconstructive techniques are associated with higher occlusion rates but a higher risk of perioperative ischemic stroke. In the reconstructive group, flow diversion carries a higher level of complete occlusion and similar clinical outcomes.

Blister-like aneurysms (BLAs) are intracranial arterial lesions originating at nonbranching sites of the dorsal supraclinoid internal carotid artery and basilar artery. BLAs account for 0.3%–1% of intracranial aneurysms and 0.9%–6.5% of ruptured aneurysms.^1–6 They are attributed to subadventitial dissections resulting in a focal wall defect with absence of internal elastic lamina and media, leading, in most cases, to acute subarachnoid hemorrhage. The arterial gap is only covered with adventitia and thin fibrinous tissue.^4,7–10Ruptured BLAs have a high mortality rate. Furthermore, treatment of these lesions is technically difficult because they often lack a defined neck and the aneurysm sac has a very thin wall.^4,11–13 Thus, ruptured BLAs are associated with high rates of spontaneous or treatment-induced rebleed and death, regardless of treatment type.^2,4,13,14Many surgical techniques such as wrapping or trapping with bypass have been described for the treatment of these lesions. However, such techniques are often associated with high perioperative morbidity and mortality rates.^{8,10,11,13,15–20} Because of these results, endovascular techniques, both reconstructive and deconstructive, have emerged as the treatment of choice due to perceived lower rates of treatment-related morbidity and higher efficacy.^{2–4,12,21–25} However, because of the rarity of these lesions, most series on endovascular treatment of BLAs are small retrospective single-center case series. Thus, the efficacy and safety of endovascular treatment of these lesions have not been well-established.⁴ In addition, little is known regarding whether reconstructive techniques with parent artery preservation are associated with similar rates of angiographic occlusion and improved clinical outcomes compared with deconstructive parent artery sacrifice.¹³ Therefore, we performed a systematic review of the literature examining the overall efficacy of endovascular treatments for ruptured BLAs and comparing outcomes of reconstructive techniques such as stent placement, flow diversion, and stent-assisted coiling with deconstructive techniques such as parent artery occlusion and trapping. We also performed a subgroup analysis comparing the safety and efficacy of flow-diverter treatment with other reconstructive techniques.     

Hydrocephalus Decreases Arterial Spin-Labeled Cerebral Perfusion

BACKGROUND AND PURPOSE:Reduced cerebral perfusion has been observed with elevated intracranial pressure. We hypothesized that arterial spin-labeled CBF can be used as a marker for symptomatic hydrocephalus.MATERIALS AND METHODS:We compared baseline arterial spin-labeled CBF in 19 children (median age, 6.5 years; range, 1–17 years) with new posterior fossa brain tumors and clinical signs of intracranial hypertension with arterial spin-labeled CBF in 16 age-matched controls and 4 patients with posterior fossa tumors without ventriculomegaly or signs of intracranial hypertension. Measurements were recorded in the cerebrum at the vertex, deep gray nuclei, and periventricular white matter and were assessed for a relationship to ventricular size. In 16 symptomatic patients, we compared cerebral perfusion before and after alleviation of hydrocephalus.RESULTS:Patients with uncompensated hydrocephalus had lower arterial spin-labeled CBF than healthy controls for all brain regions interrogated (P < .001). No perfusion difference was seen between asymptomatic patients with posterior fossa tumors and healthy controls (P = 1.000). The median arterial spin-labeled CBF increased after alleviation of obstructive hydrocephalus (P < .002). The distance between the frontal horns inversely correlated with arterial spin-labeled CBF of the cerebrum (P = .036) but not the putamen (P = .156), thalamus (P = .111), or periventricular white matter (P = .121).CONCLUSIONS:Arterial spin-labeled–CBF was reduced in children with uncompensated hydrocephalus and restored after its alleviation. Arterial spin-labeled–CBF perfusion MR imaging may serve a future role in the neurosurgical evaluation of hydrocephalus, as a potential noninvasive method to follow changes of intracranial pressure with time.

Hydrocephalus is a common neurosurgical condition in children and adults, accounting for approximately 69,000 annual hospital admissions and 39,000 shunt procedures in the United States.^1,2 While concepts of hydrocephalus remain complex, including pathophysiology, diagnostic and therapeutic approaches,^3–5 and outcome,^6,7 it is generally accepted that hydrocephalus reflects pathologic dynamics among brain, spinal cord, blood, and CSF within a confined environment.^8–10 In clinical practice, imaging is often used to work-up hydrocephalus in search of obstructing lesions or the presence of ventriculomegaly. However, ventricular size, a frequently used imaging feature, does not always correlate with underlying CSF pressures or resorptive capacity for CSF^11–16 and, therefore, may not reliably identify compensated hydrocephalus without signs of raised intracranial pressure (ICP) and progressive hydrocephalus with raised ICP.Prior studies have shown reduced CBF with elevated ICP in various animal models of hydrocephalus.^17–20 Reduced CBF has also been reported in small case series of children with either congenital hydrocephalus or acute hydrocephalus from brain tumors by using ¹⁵O-PET²¹ or SPECT.²² Recently, 2D phase-contrast MRA has shown that carotid and basilar arterial flow rates are reduced in infants with hydrocephalus.²³ However, 2D phase-contrast MRA does not directly measure CBF at the tissue level and may be hampered by long scanning times and flow-sensitive technical challenges.^24,25In contrast, arterial spin-labeled (ASL) MR imaging perfusion directly measures tissue perfusion without requiring long scanning times, contrast, or radioisotope injection.²⁶ It is also uniquely advantageous in children with high labeling efficiency and SNR and can be repeated in the event of patient motion or after CSF diversion without the risk of radiation exposure.²⁷ While ASL perfusion has increasingly become clinically available, no studies have investigated its role for evaluating hydrocephalus. We hypothesized that ASL-CBF is reduced in uncompensated hydrocephalus and improved after its alleviation and, therefore, can be used as a marker for symptomatic hydrocephalus.     

Symptom Differences and Pretreatment Asymptomatic Interval Affect Outcomes of Stenting for Intracranial Atherosclerotic Disease

BACKGROUND AND PURPOSE:Different types of symptomatic intracranial stenosis may respond differently to interventional therapy. We investigated symptomatic and pathophysiologic factors that may influence clinical outcomes of patients with intracranial atherosclerotic disease who were treated with stents.MATERIALS AND METHODS:A retrospective analysis was performed of patients treated with stents for intracranial atherosclerosis at 4 centers. Patient demographics and comorbidities, lesion features, treatment features, and preprocedural and postprocedural functional status were noted. χ² univariate and multivariate logistic regression analysis was performed to assess technical results and clinical outcomes.RESULTS:One hundred forty-two lesions in 131 patients were analyzed. Lesions causing hypoperfusion ischemic symptoms were associated with fewer strokes by last contact [χ² (1, n = 63) = 5.41, P = .019]. Nonhypoperfusion lesions causing symptoms during the 14 days before treatment had more strokes by last contact [χ² (1, n = 136), 4.21, P = .047]. Patients treated with stents designed for intracranial deployment were more likely to have had a stroke by last contact (OR, 4.63; P = .032), and patients treated with percutaneous balloon angioplasty in addition to deployment of a self-expanding stent were less likely to be stroke free at point of last contact (OR, 0.60; P = .034).CONCLUSIONS:More favorable outcomes may occur after stent placement for lesions causing hypoperfusion symptoms and when delaying stent placement 7–14 days after most recent symptoms for lesions suspected to cause embolic disease or perforator ischemia. Angioplasty performed in addition to self-expanding stent deployment may lead to worse outcomes, as may use of self-expanding stents rather than balloon-mounted stents.

Intracranial atherosclerotic disease (ICAD) causes considerable morbidity and mortality, accounting for up to one-third of ischemic strokes in some series, particularly in certain populations.^1–3 Some lesions prove recalcitrant to first-line medical management, and, in recent decades, endovascular treatments have emerged and evolved as complementary therapies.^4,5 Early series demonstrated technical feasibility and acceptable safety for percutaneous transluminal angioplasty (PTA) and then stent placement of lesions in ICAD.^5–17 Initially, intracranial procedures were performed with devices designed and approved for coronary interventions, with subsequent release of angioplasty balloons specifically engineered for intracranial use.^5,12,17–33 In 2005, the Wingspan stent system with Gateway PTA balloon catheter (Stryker, Kalamazoo, Michigan) became the first stent approved for treatment of ICAD in the United States.^{5,12,18–22,25,34} Numerous studies reported progressively improved outcomes and low complication rates, but randomized data proving efficacy were lacking.^{5,12,18,20,24,25,35,36} In 2011, enrollment in the first randomized, controlled trial to evaluate stent placement versus medical management of ICAD, the Stent placement and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) trial, was halted early due to high complication rates in the stent placement group as compared with the medical management group.⁴The results of SAMMPRIS have elicited strong responses from both proponents and detractors of stent placement, with clinical decisions now changing.⁵ This current study retrospectively analyzes results of stent placement procedures performed for ICAD at 4 centers, with attention given to factors not specifically assessed in SAMMPRIS that may help guide further investigations of endovascular ICAD management.     

Efficacy and Safety of Ethanol Ablation for Branchial Cleft Cysts

BACKGROUND AND PURPOSE:Branchial cleft cyst is a common congenital lesion of the neck. This study evaluated the efficacy and safety of ethanol ablation as an alternative treatment to surgery for branchial cleft cyst.MATERIALS AND METHODS:Between September 2006 and October 2016, ethanol ablation was performed in 22 patients who refused an operation for a second branchial cleft cyst. After the exclusion of 2 patients who were lost to follow-up, the data of 20 patients were retrospectively evaluated. All index masses were confirmed as benign before treatment. Sonography-guided aspiration of the cystic fluid was followed by injection of absolute ethanol (99%) into the lesion. The injected volume of ethanol was 50%–80% of the volume of fluid aspirated. Therapeutic outcome, including the volume reduction ratio, therapeutic success rate (volume reduction ratio of >50% and/or no palpable mass), and complications, was evaluated.RESULTS:The mean index volume of the cysts was 26.4 ± 15.7 mL (range, 3.8–49.9 mL). After ablation, the mean volume of the cysts decreased to 1.2 ± 1.1 mL (range, 0.0–3.5 mL). The mean volume reduction ratio at last follow-up was 93.9% ± 7.9% (range, 75.5%–100.0%; P < .001). Therapeutic success was achieved in all nodules (20/20, 100%), and the symptomatic (P < .001) and cosmetic (P < .001) scores had improved significantly by the last follow-up. In 1 patient, intracystic hemorrhage developed during the aspiration; however, no major complications occurred in any patient.CONCLUSIONS:Ethanol ablation is an effective and safe treatment for patients with branchial cleft cysts who refuse, or are ineligible for, an operation.

Branchial cleft cyst (BCC) is a congenital epithelial cyst, which may arise in the lateral neck. The lesions are thought to represent failed obliteration of one of the brachial clefts during embryonic development.¹ Although BCC is benign, some patients have pain, swelling, neck discomfort, and cosmetic problems. Surgery is curative in patients with BCC, but in addition to the need for general anesthesia, its drawbacks include scarring and postoperative morbidity. Therefore, minimally invasive treatment such as ultrasonography (US)-guided chemical ablation has been suggested as an alternative treatment for BCC.^2–7Both chemical ablation with picibanil (OK-432) and ethanol ablation (EA) are widely used to treat cystic lesions of the neck and oral cavity, such as thyroid cyst, ranula, and lymphatic malformation,^8–13 but only a few studies have focused on the use of either treatment in BCCs. Since Fukumoto et al² initially used EA on 3 BCCs in 1994, several studies have reported success rates of roughly 60% in patients with BCC treated with OK-432.^3–7 However, OK-432 is not widely accepted as an alternative to an operation because of its limited efficacy and adverse effects such as fever and local pain after the procedure.^3–7 In patients with thyroid cysts, EA has been recommended as a first-line treatment technique, rather than OK-432, due to its higher efficacy and safety.^14–17 However, except for a case report by Fukumoto et al, there have been no studies on the efficacy and safety of EA in BCC, to our knowledge. Therefore, in this retrospective study, we evaluated the efficacy and safety of EA for the treatment of BCC in patients from 2 hospitals (Ajou Univeristy Medical Center, Sharing and Happiness Hospital).     

The Effects of Acetazolamide on the Evaluation of Cerebral Hemodynamics and Functional Connectivity Using Blood Oxygen Level–Dependent MR Imaging in Patients with Chronic Steno-Occlusive Disease of the Anterior Circulation

BACKGROUND AND PURPOSE:Measuring cerebrovascular reactivity with the use of vasodilatory stimuli, such as acetazolamide, is useful for chronic cerebrovascular steno-occlusive disease. The purpose of this study was to evaluate the effects of acetazolamide on the assessment of hemodynamic impairment and functional connectivity by using noninvasive resting-state blood oxygen level–dependent MR imaging.MATERIALS AND METHODS:A 20-minute resting-state blood oxygen level–dependent MR imaging scan was acquired with infusion of acetazolamide starting at 5 minutes after scan initiation. A recently developed temporal-shift analysis technique was applied on blood oxygen level–dependent MR imaging data before and after acetazolamide infusion to identify regions with hemodynamic impairment, and the results were compared by using contrast agent–based DSC perfusion imaging as the reference standard. Functional connectivity was compared with and without correction on the signal by using information from temporal-shift analysis, before and after acetazolamide infusion.RESULTS:Visually, temporal-shift analysis of blood oxygen level–dependent MR imaging data identified regions with compromised hemodynamics as defined by DSC, though performance deteriorated in patients with bilateral disease. The Dice similarity coefficient between temporal-shift and DSC maps was higher before (0.487 ± 0.150 by using the superior sagittal sinus signal as a reference for temporal-shift analysis) compared with after acetazolamide administration (0.384 ± 0.107) (P = .006, repeated-measures ANOVA). Functional connectivity analysis with temporal-shift correction identified brain network nodes that were otherwise missed. The accuracy of functional connectivity assessment decreased after acetazolamide administration (P = .015 for default mode network, repeated-measures ANOVA).CONCLUSIONS:Temporal-shift analysis of blood oxygen level–dependent MR imaging can identify brain regions with hemodynamic compromise in relation to DSC among patients with chronic cerebrovascular disease. The use of acetazolamide reduces the accuracy of temporal-shift analysis and network connectivity evaluation.

The measurement of cerebral perfusion can aid in the characterization of patients with cerebral ischemic diseases.^1,2 Recent studies have demonstrated that the determination of diffusion-perfusion mismatch provides a valuable paradigm for selecting a subpopulation of patients with acute stroke most likely to benefit from reperfusion therapies.^3–8 However, MR perfusion imaging is typically based on DSC with bolus injection of a gadolinium-based contrast agent.^5,8–10 Although the risk of nephrogenic systemic fibrosis associated with the use of gadolinium-based contrast agents may be minimized through renal function screening, there are recent concerns about chronic deposition of gadolinium in the brain.¹¹ The use of a contrast agent may furthermore preclude repeat perfusion scans in the same session,¹² which are needed in clinical settings such as the evaluation of cerebrovascular reactivity.The development of noninvasive approaches without the need for contrast agent administration can provide useful alternatives. Although arterial spin-labeling is a noninvasive method for measuring CBF, it is prone to errors in regions with a long arterial transit time of blood,^12–14 which is particularly problematic in patients with steno-occlusive disease. Recently, temporal-shift (TS) analysis of the resting-state blood oxygen level–dependent MR imaging (BOLD) signal, which is sensitive to local blood flow and oxygen metabolism,¹⁵ has been shown to depict regions with cerebrovascular impairment in acute stroke and chronic cerebral hypoperfusion.^16–18 In addition, compared with the measurement of hemodynamic parameters, the assessment of the functional status of such hypoperfused brain is underinvestigated. A growing body of work supports resting-state BOLD signal possibly being used to evaluate functional brain networks.^19–23 Leveraging different aspects of the same BOLD acquisition, simultaneous assessment of cerebral hemodynamics and functional connectivity therefore becomes an attractive application of resting-state BOLD.Traditionally, cerebrovascular reactivity has been an important measure in patients with chronic steno-occlusive disease. The measurement of cerebrovascular reactivity is performed by quantifying cerebrovascular responses to vasodilatory stimuli, such as the administration of acetazolamide (ACZ) or inhalation of air with increased CO₂ concentration (eg, 5%).^24–26 Examining the effects of vasodilatory stimuli on TS and functional connectivity analyses may shed light on their physiologic basis and allow development of an operationalized approach to their evaluation. In this study, we aimed to assess the effects of ACZ on the evaluations of hemodynamic impairment and functional brain connectivity by using resting-state BOLD in patients with chronic steno-occlusive disease of the anterior circulation. We hypothesized that TS analysis of BOLD data could identify regions with hemodynamic compromise in patients with chronic cerebrovascular disease, similar to those shown in acute stroke and Moyamoya disease. We further hypothesized that the use of ACZ would affect the results of TS and functional connectivity analyses due to its alteration in neurovascular coupling.     

The Impact of Arterial Collateralization on Outcome after Intra-Arterial Therapy for Acute Ischemic Stroke

BACKGROUND AND PURPOSE:Although intra-arterial therapy for acute ischemic stroke is associated with superior recanalization rates, improved clinical outcomes are inconsistently observed following successful recanalization. There is emerging concern that unfavorable arterial collateralization, though unproven, predetermines poor outcome. We hypothesized that poor leptomeningeal collateralization, assessed by preprocedural CTA, is associated with poor outcome in patients with acute ischemic stroke undergoing intra-arterial therapy.MATERIALS AND METHODS:We retrospectively analyzed patients with acute ischemic stroke with intracranial ICA and/or MCA occlusions who received intra-arterial therapy. The collaterals were graded on CTA. Univariate and multivariate analyses were used to investigate the association between the dichotomized leptomeningeal collateral score and functional outcomes at 3-months mRS ≤2, mortality, and intracranial hemorrhages.RESULTS:Eighty-seven patients were included. The median age was 66 years (interquartile range, 54–76 years) and the median NIHSS score at admission was 18 (interquartile range, 14–20). The leptomeningeal collateral score 3 was found to have significant association with the good functional outcome at 3 months: OR = 3.13; 95% CI, 1.25–7.825; P = .016. This association remained significant when adjusted for the use of IV tissue plasminogen activator: alone, OR = 2.998; 95% CI, 1.154–7.786; P = .024; and for IV tissue plasminogen activator and other confounders (age, baseline NIHSS score, and Thrombolysis in Cerebral Infarction grades), OR = 2.985; 95% CI, 1.027–8.673; P = .045.CONCLUSIONS:We found that poor arterial collateralization, defined as a collateral score of <3, was associated with poor outcome, after adjustment for recanalization success. We recommend that future studies include collateral scores as one of the predictors of functional outcome.

Intravenous tissue plasminogen activator is the only proved reperfusion therapy for acute ischemic stroke. However, a narrow therapeutic time window (<4.5 hours) limits its use because the clinical effectiveness is critically time-dependent.^1–3 In addition, recanalization rates with IV-tPA are low in the setting of large-artery occlusion, (eg, ICA occlusion <10%).^4–6 Intra-arterial therapy (IAT) has higher recanalization rates than intravenous thrombolysis, but this result has not been matched by concordant improvement in clinical outcomes.^7–9 Two recent randomized trials comparing IAT with IV-tPA, the Interventional Management of Stroke III trial and the Local versus Systemic Thrombolysis for Acute Ischemic Stroke trial, did not demonstrate superiority.^10,11Inadequate arterial collateralization is a possible mechanism to explain the mismatch between recanalization success and clinical outcome, apart from the presence of an already infarcted ischemic core and an incomplete microcirculatory reperfusion after focal cerebral ischemia.^12,13 A favorable arterial collateralization as determined by a robust leptomeningeal anastomoses profile may enhance recanalization, improve downstream reperfusion, reduce the extent of infarct core and ischemic lesion growth, decrease hemorrhagic transformation, and improve outcome postrevascularization.^14–16The leptomeningeal collateral scoring system based on CTA correlates with clinical outcome.^17–21 However, its role in IAT is unclear. We hypothesized that a poor leptomeningeal CTA score predicts clinical futility in patients undergoing IAT independent of recanalization status.     

Autosomal Dominant Polycystic Kidney Disease and Intracranial Aneurysms: Is There an Increased Risk of Treatment?

BACKGROUND AND PURPOSE:Autosomal dominant polycystic kidney disease is associated with an increased risk of intracranial aneurysms. Our purpose was to assess whether there is an increased risk during aneurysm coiling and clipping.MATERIALS AND METHODS:Data were obtained from the National Inpatient Sample (2000–2011). All subjects had an unruptured aneurysm clipped or coiled and were divided into polycystic kidney (n = 189) and control (n = 3555) groups. Primary end points included in-hospital mortality, length of stay, and total hospital charges. Secondary end points included the International Classification of Diseases, Ninth Revision codes for iatrogenic hemorrhage or infarction; intracranial hemorrhage; embolic infarction; and carotid and vertebral artery dissections.RESULTS:There was a significantly greater incidence of iatrogenic hemorrhage or infarction, embolic infarction, and carotid artery dissection in the patients with polycystic kidney disease compared with the control group after endovascular coiling. There was also a significantly greater incidence of iatrogenic hemorrhage or infarction in the polycystic kidney group after surgical clipping. However, the hospital stay was not longer in the polycystic kidney group, and the total hospital charges were not higher. Additional analysis within the polycystic kidney group revealed a significantly shorter length of stay but similar in-hospital costs when subjects underwent coiling versus clipping.CONCLUSIONS:Patients with polycystic kidney disease face an increased risk during intracranial aneurysm treatment, whether by coiling or clipping. This risk, however, does not translate into longer hospital stays or increased hospital costs. Despite the additional catheterization-related risks of dissection and embolization, coiling results in shorter hospital stays and similar mortality compared with clipping.

Autosomal dominant polycystic kidney disease (ADPCKD) is a genetic disorder affecting 1 in 1000 individuals worldwide and is associated with an increased risk of intracranial aneurysms, ranging from 4% to 23%^1–6 compared with the general population risk of 2%–3%.^7–10 Patients with ADPCKD are also at increased risk for aneurysm rupture earlier in life (mean age, 35–45 years),^1,11–13 compared with the general population (mean age, 50–54 years).^14,15There is evidence that the associated vascular defects in ADPCKD may be due to mutations in the PKD1 and PKD2 genes, located on the short arm of chromosomes 16 and 4.^16,17 Abnormalities of these genes in mouse models correspond with increased rates of arterial dissection, arterial rupture, and intracranial vascular abnormalities.¹⁸ To our knowledge, only 1 study to date has investigated whether these issues engender an increased risk when treating intracranial aneurysms (whether by endovascular coiling or surgical clipping).² The purpose of this investigation was to assess whether ADPCKD confers an increased peri- and immediate postprocedural risk of aneurysm coiling and clipping.     

Automatic Quantification of Subarachnoid Hemorrhage on Noncontrast CT

BACKGROUND AND PURPOSE:Quantification of blood after SAH on initial NCCT is an important radiologic measure to predict patient outcome and guide treatment decisions. In current scales, hemorrhage volume and density are not accounted for. The purpose of this study was to develop and validate a fully automatic method for SAH volume and density quantification.MATERIALS AND METHODS:The automatic method is based on a relative density increase due to the presence of blood from different brain structures in NCCT. The method incorporates density variation due to partial volume effect, beam-hardening, and patient-specific characteristics. For validation, automatic volume and density measurements were compared with manual delineation on NCCT images of 30 patients by 2 radiologists. The agreement with the manual reference was compared with interobserver agreement by using the intraclass correlation coefficient and Bland-Altman analysis for volume and density.RESULTS:The automatic measurement successfully segmented the hemorrhage of all 30 patients and showed high correlation with the manual reference standard for hemorrhage volume (intraclass correlation coefficient = 0.98 [95% CI, 0.96–0.99]) and hemorrhage density (intraclass correlation coefficient = 0.80 [95% CI, 0.62–0.90]) compared with intraclass correlation coefficient = 0.97 (95% CI, 0.77–0.99) and 0.98 (95% CI, 0.89–0.99) for manual interobserver agreement. Mean SAH volume and density were, respectively, 39.3 ± 31.5 mL and 62.2 ± 5.9 Hounsfield units for automatic measurement versus 39.7 ± 32.8 mL and 61.4 ± 7.3 Hounsfield units for manual measurement. The accuracy of the automatic method was excellent, with limits of agreement of −12.9–12.1 mL and −7.6–9.2 Hounsfield units.CONCLUSIONS:The automatic volume and density quantification is very accurate compared with manual assessment. As such, it has the potential to provide important determinants in clinical practice and research.

Despite improvements, the treatment of SAH is associated with high fatality rates and affects fairly young adults: up to half of all cases of SAH are fatal within 30 days, and the mean age of presentation is 55 years.^1–5 There is strong agreement among studies that the amount of subarachnoid blood on initial NCCT has a highly predictive value regarding patient outcome and the incidence of vasospasm and concomitant delayed cerebral ischemia.^3,4,6–9 Hemorrhagic density may be of equal importance in predicting patient outcome, but this has not been validated properly.^3,10–12 Currently several grading systems are used to assess the initial clinical and radiologic features of SAH.^7,8,13–15 However, there is still an ongoing discussion about the optimal method of grading SAH on NCCT.^3,7,16–18 The 2 most commonly used scales of Fisher et al⁷ and Hijdra et al⁸ have come under criticism; authors referred to these scales as rather gross estimators, difficult to apply, lacking quantification, and cumbersome in the clinical setting.^3,17,19–22 Moreover, hemorrhage density is not considered in these scales. A quantitative volume and density measurement may reduce interobserver variability in comparison with current scales and would provide physicians with a potentially valuable tool for outcome prediction and treatment guidance.²³ As such, the aim of this study was to design and validate a reliable and easy-to-apply automatic measurement for subarachnoid hemorrhage quantification.