The urothelial barrier in interstitial cystitis/bladder pain syndrome: its form and function, an overview of preclinical models.

PURPOSE OF REVIEW: Investigating bladder pain syndrome/interstitial cystitis (IC/BPS) preclinically is challenging. Various research models have been used to mimic the urothelial barrier closely and replicate the disease. The aim of this review is to discuss preclinical research related to the urothelial barrier in context of IC/BPS. RECENT FINDINGS: In vivo models mimic IC/BPS mainly with toxic substances in the urine, with protaminesulfate and proteoglycan deglycolysation resembling a temporary impaired barrier as seen in IC/BPS. This temporary increased permeability has also been found in vitro models. Glycosaminoglycan replenishment therapy has been described, in vivo and in vitro, to protect and enhance recover properties of the urothelium. The roles of immune and neurogenic factors in the pathogenesis of IC/BPS remains relatively understudied. SUMMARY: Preclinical studies provide opportunities to identify the involvement of specific pathologic pathways in IC/BPS. For further research is warranted to elucidate the primary or secondary role of permeability, together with inflammatory and neurogenic causes of the disease.

Microvascular reperfusion during endovascular therapy: the balance of supply and demand.

BACKGROUND: Endovascular therapy (EVT) has revolutionized the treatment of acute stroke, but large vessel recanalization does not always result in tissue-level reperfusion. Cerebral blood flow (CBF) is not routinely monitored during EVT. We aimed to leverage diffuse correlation spectroscopy (DCS), a novel transcranial optical imaging technique, to assess the relationship between microvascular CBF and post-EVT outcomes. METHODS: Frontal lobe CBF was monitored by DCS in 40 patients undergoing EVT. Baseline CBF deficit was calculated as the percentage of CBF impairment on pre-EVT CT perfusion. Microvascular reperfusion was calculated as the percentage increase in DCS-derived CBF that occurred with recanalization. The adequacy of reperfusion was defined by persistent CBF deficit, calculated as: baseline CBF deficit - microvascular reperfusion. A good functional outcome was defined as 90-day modified Rankin Scale score ≤2. RESULTS: Thirty-six of 40 patients achieved successful recanalization, in whom microvascular reperfusion in itself was not associated with infarct volume or functional outcome. However, patients with good functional outcomes had a smaller persistent CBF deficit (median 1% (IQR -11%-16%)) than patients with poor outcomes (median 28% (IQR 2-50%)) (p=0.02). Smaller persistent CBF deficit was also associated with smaller infarct volume (p=0.004). Multivariate models confirmed that persistent CBF deficit was independently associated with infarct volume and functional outcome. CONCLUSIONS: CBF augmentation alone does not predict post-EVT outcomes, but when microvascular reperfusion closely matches the baseline CBF deficit, patients experience favorable clinical and radiographic outcomes. By recognizing inadequate reperfusion, bedside CBF monitoring may provide opportunities to personalize post-EVT care aimed at CBF optimization.

Intraoperative angiography in neurosurgery: temporal trend, access site, and operative indication considerations from a 6-year institutional experience.

BACKGROUND: Historically, the transfemoral approach (TFA) has been the most common access site for cerebral intraoperative angiography (IOA). However, in line with trends in cardiac interventional vascular access preferences, the transradial approach (TRA) and transulnar approach (TUA) have been gaining popularity owing to favorable safety and patient satisfaction outcomes. OBJECTIVE: To compare the efficacy and safety of TRA/TUA and TFA for cerebral and spinal IOA at an institutional level over a 6-year period. METHODS: Between July 2016 and December 2022, 317 angiograms were included in our analysis, comprising 60 TRA, 10 TUA, 243 TFA, and 4 transpopliteal approach cases. Fluoroscopy time, contrast dose, reference air kerma, and dose-area products per target vessel catheterized were primary endpoints. Multivariate regression analyses were conducted to evaluate predictors of elevated contrast dose and radiation exposure and to assess time trends in access site selection. RESULTS: Contrast dose and radiation exposure metrics per vessel catheterized were not significantly different between access site groups when controlling for patient position, operative region, 3D rotational angiography use, and different operators. Access site was not a significant independent predictor of elevated radiation exposure or contrast dose. There was a significant relationship between case number and operative indication over the study period (P<0.001), with a decrease in the proportion of cases for aneurysm treatment offset by increases in total cases for the management of arteriovenous malformation, AVF, and moyamoya disease. CONCLUSIONS: TRA and TUA are safe and effective access site options for neurointerventional procedures that are increasingly used for IOA.

Expanding Glycomic Investigations through Thiol-Derivatized Glycans.

N-(2-thioethyl)-2-aminobenzamide (TEAB), a novel glycan auxiliary, was synthesized and its utility was evaluated. The auxiliary was conjugated to glycans by reductive amination with the water-stable reagent 2-picoline borane complex. Glycan products, which ranged from 1 to 7 linked hexoses, were all isolated in yields ranging from 60% to 90% after purification by reverse-phase chromatography. The novel conjugate introduces a convenient, shelf-stable thiol directly onto the desired free glycans with purification advantages and direct modification with efficient reactions through alkenes, halides, epoxides, disulfides, and carboxylates in yields of 49% to 93%. Subsequently, a thiol-selective modification of the BSA protein was used to generate a neoglycoprotein with a bifunctional PEG-maleimide linker. To further illustrate the utility of a thiol motif, 2-thiopyridine activation of a thiol-containing support facilitated the covalent chromatographic purification of labeled glycans in yields up to 63%. Finally, initial proof of concept of implementation in a light printed microarray was explored and validated through FITC-labeled concanavalin A binding. In conclusion, the thiol-functionalized glycans produced greatly expand the diversity of bioconjugation tools that can be developed with glycans and enable a variety of biological investigations.

Highly Visible Wall-Timer to Reduce Endovascular Treatment Time for Stroke.

BACKGROUND: Endovascular therapy for acute ischemic stroke has revolutionized clinical care for patients with stroke and large vessel occlusion, but treatment remains time sensitive. At our stroke center, up to half of the door-to-groin time is accounted for after the patient arrives in the angio-suite. Here, we apply the concept of a highly visible timer in the angio-suite to quantify the impact on endovascular treatment time. METHODS: This was a single-center prospective pseudorandomized study conducted over a 32-week period. Pseudorandomization was achieved by turning the timer on and off in 2-week intervals. The primary outcome was angio-suite-to-groin time, and secondary outcomes were angio-suite-to-intubation time, groin-to-recanalization time, and 90-day modified Rankin scale. A stratified analysis was performed based on type of anesthesia (ie, endotracheal intubation versus not). RESULTS: During the 32-week study period, 97 mechanical thrombectomies were performed. The timer was on and off for 38 and 59 cases, respectively. The timer resulted in faster angio-suite-to-groin time (28 versus 33 minutes; P=0.02). The 5-minute reduction in angio-suite-to-groin was maintained after adjusting for intubation status in a multivariate regression (P=0.02). There was no difference in the 90-day modified Rankin scale between groups. The timer impact was consistent across the 32-week study period. CONCLUSIONS: A highly visible timer in the angio-suite achieved a meaningful, albeit modest, reduction in endovascular treatment time for patients with stroke. Given the lack of risk and low cost, it is reasonable for stroke centers to consider a highly visible timer in the angio-suite to improve treatment times.

Artery of Davidoff and Schechter: A Large Angiographic Case Series of Dural AV Fistulas.

The artery of Davidoff and Schechter (ADS) is the only meningeal branch of the posterior cerebral artery (PCA), supplying the medial tentorial margin and posterior portions of the falx. Given its small size, it is rarely identified on angiographic studies, unless enlarged in pathologies such as dural arteriovenous fistulas (DAVFs) or vascularized masses. This artery was first described by Wollschlaeger and Wollschlaeger in 1965, and to date, only a few reports have described its significance. The objective of this study is to report our experience with the ADS in dural fistulas from 2 tertiary medical centers and to emphasize the importance of recognizing this artery during angiographic examination of vascular tentorial and posterior fossa lesions. To our knowledge, this report demonstrates the largest angiographic case series published to date, recognizing a total of 7 patients with ADS arising secondary to a posterior fossa or tentorial DAVF and one of the largest reported series of DAVFs supplied by the ADS treated by endovascular and surgical techniques. Our cases validate the importance of prompt identification of the ADS for the diagnosis as well as endovascular treatment of vascular malformations in the posterior fossa and tentorial region.

Singlet Oxygen Activatable Prodrugs of Paclitaxel, SN-38, MMC and CA4: Nonmitochondria-Targeted Prodrugs.

We established a light-activatable prodrug strategy that produces the combination effect of photodynamic therapy (PDT) and site-specific chemotherapy. Prodrugs are activated by singlet oxygen (SO), generated from PS and visible or near IR light, in either intra- or inter-molecular manner. The goal of this study is to evaluate cytotoxic effects of nonmitochondria-targeted prodrugs of a number of anticancer drugs with different mechanisms of action. They were tested in both 2D and 3D in vitro conditions via inter-molecular activation of prodrugs by SO generated in mitochondria by protoporphyrin IX-PDT (PpIX-PDT). Prodrugs of anticancer drugs (paclitaxel, SN-38, combretastatin A4 and mitomycin C) were synthesized using facile and high-yielding reactions. Nonmitochondria-targeted prodrugs showed limited dark toxicity while all of them showed greatly enhanced phototoxicity compared to PpIX-PDT in the 2D culture model. Prodrugs generated up to about 95% cell killing at 2.5 µM when administered with hexyl-aminolevulinate (HAL) to produce Protoporphyrin IX in cancer cells in both 2D monolayer and 3D spheroids model. The data demonstrate that mitochondria-targeting of prodrugs is not fully essential for our inter-molecular activation prodrug strategy. The prodrug strategy also worked for anticancer drugs with diverse MOAs.

MRI as a Tool to Assess Interstitial Cystitis Associated Bladder and Brain Pathologies.

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic, often incapacitating condition characterized by pain seeming to originate in the bladder in conjunction with lower urinary tract symptoms of frequency and urgency, and consists of a wide range of clinical phenotypes with diverse etiologies. There are currently no diagnostic tests for IC/BPS. Magnetic resonance imaging (MRI) is a relatively new tool to assess IC/BPS. There are several methodologies that can be applied to assess either bladder wall or brain-associated alterations in tissue morphology and/or pain. IC/BPS is commonly associated with bladder wall hyperpermeability (BWH), particularly in severe cases. Our group developed a contrast-enhanced magnetic resonance imaging (CE-MRI) approach to assess BWH in preclinical models for IC/BPS, as well as for a pilot study for IC/BPS patients. We have also used the CE-MRI approach to assess possible therapies to alleviate the BWH in preclinical models for IC/BPS, which will hopefully pave the way for future clinical trials. In addition, we have used molecular-targeted MRI (mt-MRI) to quantitatively assess BWH biomarkers. Biomarkers, such as claudin-2, may be important to assess and determine the severity of BWH, as well as to assess therapeutic efficacy. Others have also used other MRI approaches to assess the bladder wall structural alterations with diffusion-weighted imaging (DWI), by measuring changes in the apparent diffusion coefficient (ADC), diffusion tensor imaging (DTI), as well as using functional MRI (fMRI) to assess pain and morphological MRI or DWI to assess anatomical or structural changes in the brains of patients with IC/BPS. It would be beneficial if MRI-based diagnostic tests could be routinely used for these patients and possibly used to assess potential therapeutics.

Balloon occlusion as an adjunctive technique during sclerotherapy of Puig's classified advanced venous malformations.

OBJECTIVE: Puig types 2 through 4 venous malformations (VMs) are challenging to treat with sclerotherapy given their robust systemic outflow. Endovenous balloon occlusion offers a means of temporarily occluding systemic venous outflow to allow for more complete sclerotherapy. This study reviews our experience of implementing this technique in patients with Puig advanced (types 2 through 4) VMs. METHODS: An IRB approved review of treated venous malformations from 2013-2016 revealed 10 patients fitting inclusion criteria. Patient demographics, pre-procedural imaging, intra-procedural technical parameters, and post-procedural follow-up outcomes were recorded. All patients underwent temporary balloon occlusion of a systemic or major draining vein during sclerotherapy. Embolic agents included n-butyl cyanoacrylate glue, sodium tetradecyl sulfate foam, and coils. Standard 5 French angioplasty balloons ranged from 4 to 8 mm diameter and 2 to 8 cm length depending on vessel requiring occlusion. All patients underwent minimum 3-year follow-up questionnaire administration re-assessing resolution of lesion symptomology and post-procedural quality of life (QoL) measures. RESULTS: Of the 10 VMs treated, 2 were Type 2, 6 were Type 3, and 2 were Type 4. More than one sclerotherapy session was required in 7/10 patients (mean: 2, range: 1-4). Most common sites of VM systemic drainage included subclavian, popliteal, internal/external jugular, and basilic veins. All patients had no indication for further sclerotherapy following adjunctive balloon occlusion. No non-target embolization or immediate post-procedural complications occurred. Follow-up questionnaires (mean interval: 3 years 6 months, range: 3 years-3 years 11 months) confirmed the persistence of embolization effects, improved QoL, and no additional sclerotherapy sessions for all patients in the cohort. CONCLUSIONS: Endovenous balloon occlusion as an adjunct to sclerotherapy can be considered when treating patients with types 2-4 venous malformations. This technique lowers the risk of non-target systemic venous embolization, allowing for operator-driven deeper intralesional sclerosant penetration and subsequently maintained treatment efficacy.

Innovative Approaches in the Battle Against Cancer Recurrence: Novel Strategies to Combat Dormant Disseminated Tumor Cells.

Cancer recurrence remains a great fear for many cancer survivors following their initial, apparently successful, therapy. Despite significant improvement in the overall survival of many types of cancer, metastasis accounts for ~90% of all cancer mortality. There is a growing understanding that future therapeutic practices must accommodate this unmet medical need in preventing metastatic recurrence. Accumulating evidence supports dormant disseminated tumor cells (DTCs) as a source of cancer recurrence and recognizes the need for novel strategies to target these tumor cells. This review presents strategies to target dormant quiescent DTCs that reside at secondary sites. These strategies aim to prevent recurrence by maintaining dormant DTCs at bay, or eradicating them. Various approaches are presented, including: reinforcing the niche where dormant DTCs reside in order to keep dormant DTCs at bay; promoting cell intrinsic mechanisms to induce dormancy; preventing the engagement of dormant DTCs with their supportive niche in order to prevent their reactivation; targeting cell-intrinsic mechanisms mediating long-term survival of dormant DTCs; sensitizing dormant DTCs to chemotherapy treatments; and, inhibiting the immune evasion of dormant DTCs, leading to their demise. Various therapeutic approaches, some of which utilize drugs that are already approved, or have been tested in clinical trials and may be considered for repurposing, will be discussed. In addition, clinical evidence for the presence of dormant DTCs will be reviewed, along with potential prognostic biomarkers to enable the identification and stratification of patients who are at high risk of recurrence, and who could benefit from novel dormant DTCs targeting therapies. Finally, we will address the shortcomings of current trial designs for determining activity against dormant DTCs and provide novel approaches.

Transformation of aldehydes into nitriles in an aqueous medium using O-phenylhydroxylamine as the nitrogen source.

The conversion of an aldehyde into a nitrile can be efficiently performed using O-phenylhydroxylamine hydrochloride in buffered aqueous solutions. The reported method is specifically optimized for aqueous-soluble substrates including carbohydrates. Several reducing sugars including monosaccharides, disaccharides, and silyl-protected saccharides were transformed into cyanohydrins in high yields. The reaction conditions are also suitable for the formation of nitriles from various types of hydrophobic aldehyde substrates. Furthermore, cyanide can be eliminated from cyanohydrins, analogous to the Wohl degradation, by utilizing a readily-removed weakly basic resin as a promoter.

SuperGAG biopolymers for treatment of excessive bladder permeability.

Few therapeutic options exist for treatment of IC/BPS. A novel high MW GAG biopolymer ("SuperGAG") was synthesized by controlled oligomerization of CS, purified by TFF and characterized by SEC-MALLS and 1H-NMR spectroscopy. The modified GAG biopolymer was tested in an OVX female rat model in which bladder permeability was induced by a 10-minute intravesicular treatment with dilute (1 mg/ml) protamine sulfate and measured by classical Ussing Chamber TEER measurements following treatment with SuperGAG, chondroitin sulfate, or saline. The effect on abrogating the abdominal pain response was assessed using von Frey filaments. The SuperGAG biopolymer was then investigated in a second, genetically modified mouse model (URO-MCP1) that increasingly is accepted as a model for IC/BPS. Permeability was induced with a brief exposure to a sub-noxious dose of LPS and was quantified using contrast-enhanced MRI (CE-MRI). The SuperGAG biopolymer restored impermeability to normal levels in the OVX rat model as measured by TEER in the Ussing chamber and reduced the abdominal pain response arising from induced permeability. Evaluation in the URO-MCP1 mouse model also showed restoration of bladder impermeability and showed the utility of CE-MRI imaging for evaluating the efficacy of agents to restore bladder impermeability. We conclude novel high MW SuperGAG biopolymers are effective in restoring urothelial impermeability and reducing pain produced by loss of the GAG layer on the urothelium. SuperGAG biopolymers could offer a novel and effective new therapy for IC/BPS, particularly if combined with MRI to assess the efficacy of the therapy.

Impact of carotid tortuosity on outcome after endovascular thrombectomy.

BACKGROUND AND OBJECTIVES: Endovascular thrombectomy (EVT) is efficacious in patients with large vessel occlusion stroke (LVO). We explored whether internal carotid (ICA) tortuosity increases the technical difficulty of EVT thereby lowering the chances of successful recanalization and favorable outcomes. PATIENTS AND METHODS: Consecutive patients with LVO and patent ICAs who underwent EVT were included. Carotid tortuosity was determined on pre-EVT CTA and classified by raters blinded to outcomes into: type 1-straight ICA trunk and type 2-severe tortuosity potentially impeding adequate catheter placement. Thrombolysis in cerebral infarction (TICI) 2b-3 was considered successful recanalization, and 90-day-modified Rankin Scale ≤ 2 was considered favorable functional outcome. RESULTS: Among 302 patients (mean age 70 ± 15, median NIHSS 17), 53% had type 1, and 47% type 2 tortuosity. Overall, 85% had successful recanalization. Patients with type 2 tortuosity were significantly older (p < 0.0001) and less frequently achieved successful recanalization (80% vs. 90%; p = 0.019) but had similar outcomes compared with those without tortuosity. On regression analysis, marked tortuosity was associated with lower chances of successful recanalization (OR 0.43 95% CI 0.20-0.92) but had no effect on clinical outcomes. CONCLUSIONS: Carotid tortuosity does not appear to impact the likelihood of favorable functional outcome but may influence recanalization.

In vivo and ex vivo assessment of bladder hyper-permeability and using molecular targeted magnetic resonance imaging to detect claudin-2 in a mouse model for interstitial cystitis.

OBJECTIVES: To determine if the URO-MCP-1 mouse model for bladder IC/BPS is associated with in vivo bladder hyper-permeability, as measured by contrast-enhanced MRI (CE-MRI), and assess whether molecular-targeted MRI (mt-MRI) can visualize in vivo claudin-2 expression as a result of bladder hyper-permeability. Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic, painful condition of the bladder that affects primarily women. It is known that permeability plays a substantial role in IC/BPS. Claudins are tight junction membrane proteins that are expressed in epithelia and endothelia and form paracellular barriers and pores that determine tight junction permeability. Claudin-2 is a molecular marker that is associated with increased hyperpermeability in the urothelium. MATERIALS AND METHODS: CE-MRI was used to measure bladder hyper-permeability in the URO-MCP-1 mice. A claudin-2-specific mt-MRI probe was used to assess in vivo levels of claudin-2. The mt-MRI probe consists of an antibody against claudin-2 conjugated to albumin that had Gd-DTPA (gadolinium diethylenetriamine pentaacetate) and biotin attached. Verification of the presence of the mt-MRI probe was done by targeting the biotin moiety for the probe with streptavidin-horse radish peroxidase (SA-HRP). Trans-epithelial electrical resistance (TEER) was also used to assess bladder permeability. RESULTS: The URO-MCP-1 mouse model for IC/BPS was found to have a significant increase in bladder permeability, following liposaccharide (LPS) exposure, compared to saline-treated controls. mt-MRI- and histologically-detectable levels of the claudin-2 probe were found to increase with LPS -induced bladder urothelial hyper-permeability in the URO-MCP-1 IC mouse model. Levels of protein expression for claudin-2 were confirmed with immunohistochemistry and immunofluorescence imaging. Claudin-2 was also found to highly co-localize with zonula occlidens-1 (ZO-1), a tight junction protein. CONCLUSION: The combination of CE-MRI and TEER approaches were able to demonstrate hyper-permeability, a known feature associated with some IC/BPS patients, in the LPS-exposed URO-MCP-1 mouse model. This MRI approach could be clinically translated to establish which IC/BPS patients have bladder hyper-permeability and help determine therapeutic options. In addition, the in vivo molecular-targeted imaging approach can provide invaluable information to enhance our understanding associated with bladder urothelium hyper-permeability in IC/BPS patients, and perhaps be used to assist in developing further therapeutic strategies.

Neuroendovascular Treatment of Acute Stroke During COVID-19: A Guide From the Frontlines.

Since the initial reports surfaced of a novel coronavirus causing illness and loss of life in Wuhan, China, COVID-19 has rapidly spread across the globe, infecting millions and leaving hundreds and thousands dead. As hospitals cope with the influx of patients with COVID-19, new challenges have arisen as health-care systems care for patients with COVID-19 while still providing essential emergency care for patients with acute strokes and acute myocardial infarction. Adding to this complex scenario are new reports that patients with COVID-19 are at increased risk of thromboembolic complications including strokes. In this article, we detail our experience caring for acute stroke patients and provide some insight into neurointerventional workflow modifications that have helped us adapt to the COVID-19 era.

Vascular imaging of the spine in the US Medicare population: Catheter and MR angiography volumes from 2004 to 2016.

AIMS: The purpose of our study was to analyze utilization trends and physician specialty distribution in spinal catheter angiography and magnetic resonance angiography in the Medicare fee-for-service population. METHODS: Data from the CMS Physician/Supplier Procedure Summary Master Files for 2004 to 2016 were used for this study. The Current Procedural Terminology version 4 codes for spinal magnetic resonance angiography (72159) and spinal catheter angiography (75705) were used to analyze the volumes of these procedures. Using Medicare's 108 specialty code, we compared procedure volumes among physician specialties. Data analysis was performed using SAS version 9.3 for Windows. RESULTS: The volume of spinal catheter angiography performed was 4758 in 2004, peaked at 6869 in 2012, and dropped to 6656 in 2016. Overall, the volume of spinal catheter angiography increased by 40% from 2004 to 2016. Radiologists performed the majority of these procedures (3736 or 56.1%) in 2016, followed by neurosurgeons (2456 or 36.9%), and neurologists (346 or 5.2%). The spinal magnetic resonance angiography volume fluctuated between 0 and 1 from 2004 to 2009, then precipitously increased to 40 in 2010, peaked at 133 in 2011, and declined to 81 in 2016. The volume of spinal magnetic resonance angiography procedures increased by 8000% from 2004 to 2016, with radiologists performing the majority of them. CONCLUSION: Our results show that spinal catheter angiography volumes continue to rise in the Medicare fee-for-service population, and are largely performed by radiologists, neurosurgeons, and neurologists. Although spinal magnetic resonance angiography volumes have started to increase, they comprise only a small fraction of studies performed for vascular evaluation of the spine.

Assessing bladder hyper-permeability biomarkers in vivo using molecularly-targeted MRI.

The objective was to investigate if some of the key molecular players associated with bladder hyper-permeability in interstitial cystitis/bladder pain syndrome (IC/BPS) could be visualized with molecularly-targeted magnetic resonance imaging (mt-MRI) in vivo. IC/BPS is a chronic, painful condition of the bladder that affects primarily women. It has been demonstrated over the past several decades that permeability plays a substantial role in IC/BPS. There are several key molecular markers that have been associated with permeability, including glycolsaminoglycan (GAG), biglycan, chondroitin sulfate, decorin, E-cadherin, keratin 20, uroplakin, vascular endothelial growth factor receptor 1 (VEGF-R1), claudin-2 and zonula occludens-1 (ZO-1). We used in vivo molecularly-targeted MRI (mt-MRI) to assess specific urothelial biomarkers (decorin, VEGF-R1, and claudin-2) associated with bladder hyper-permeability in a protamine sulfate (PS)-induced rat model. The mt-MRI probes consisted of an antibody against either VEGF-R1, decorin or claudin-2 conjugated to albumin that had also Gd-DTPA (gadolinium diethylene triamine penta acetic acid) and biotin attached. mt-MRI- and histologically-detectable levels of decorin and VEGF-R1 were both found to decrease following PS-induced bladder urothelial hyper-permeability, whereas claudin-2, was found to increase in the rat PS model. Verification of the presence of the mt-MRI probes were done by targeting the biotin moiety for each respective probe with streptavidin-hose radish peroxidase (HRP). Levels of protein expression for VEGF-R1, decorin and claudin-2 were confirmed with immunohistochemistry. In vivo molecularly-targeted MRI (mt-MRI) was found to successfully detect alterations in the expression of decorin, VEGFR1 and claudin-2 in a PS-induced rat bladder permeability model. This in vivo molecularly-targeted imaging approach has the potential to provide invaluable information to enhance our understanding of bladder urothelium hyper-permeability in IC/BPS patients, and perhaps be used to assist in developing novel therapeutic strategies.

Association of intracranial arteriovenous malformation embolization with more rapid rate of perfusion in the peri-nidal region on color-coded quantitative digital subtraction angiography.

BACKGROUND: Hemodynamic alterations post-embolization of intracranial arteriovenous malformations (AVMs) may cause delayed edema/hemorrhage in brain parenchyma adjacent to the lesion. OBJECTIVE: To quantify and compare cerebral perfusion changes in the peri-AVM territory pre- and post-embolization using color-coded quantitative digital subtraction angiography (q-DSA). METHODS: Pediatric intracranial AVM embolization procedures performed over a 5 year period were included. DSA images of all patients were retrospectively assessed using syngo iFlow. Regions of interest (ROI) were selected on anteroposterior and lateral q-DSA views: three in the peri-AVM region; two in parenchyma distant from the AVM. Time-to-peak (TTP) contrast enhancement of ROIs and ∆TTP (TTP at the selected ROI minus TTP at either the ipsilateral internal carotid/vertebral artery) were measured. RESULT: 19 pediatric patients with 19 AVMs (9 males/10 females, mean age 12 years) underwent intracranial AVM embolization: 15/19 AVMs were supplied by the anterior circulation and 4/19 by the posterior circulation. Blood flow was significantly slower post-embolization in the draining vein (19/19) (p<0.01), and the venous sinus outflow (17/19) (p<0.01), by mean difference of 2.01±1.31 s and 1.74±2.04 s. There was significantly increased peri-AVM parenchymal perfusion post-embolization (∆TTP=2.20±0.48 s) compared with pre-embolization (∆TTP=2.52±0.42 s), by an average ∆TTP of 0.33±0.53 s (p=0.014). In contrast, there was no perfusion difference (∆TTP=0.03±0.20 s, p=0.8) between pre- and post-embolization in the distant parenchyma. The size of the AVM was not correlated with change in peri-nidal parenchymal perfusion (r=-0.136, p=0.579). CONCLUSION: This study demonstrates more rapid perfusion in the peri-nidal brain parenchyma post-embolization of the AVM, which supports the theory that increased perfusion in normal tissue surrounding the AVM after embolization may underlie some post-procedural complications.

Type V Dural Arteriovenous Fistula Supplied by the Artery of Wollschlaeger and Wollschlaeger Causing Cervical Myelopathy and Quadriparesis.

BACKGROUND: The artery of Wollschlaeger and Wollschlaeger is a tentorial branch of the superior cerebellar artery that is usually not visualized on conventional cerebral angiography, unless it is pathologically enlarged. It can be recruited as part of the blood supply to tentorial dural arteriovenous fistulas (AVFs), although this occurs infrequently. CASE DESCRIPTION: Here we report the clinico-radiologic evaluation and treatment of a 48-year-old man referred to our institution for hitherto workup negative progressive, relapsing quadriparesis. This represents the first reported case of cervical myelopathy caused by venous congestion from a type V dural AVF supplied by the artery of Wollschlaeger and Wollschlaeger. CONCLUSIONS: The anatomic discrepancy between the symptomatic spinal cord lesion and the etiologic intracranial fistula frequently results in delayed care in cases of myelopathy due to intracranial dural AVFs. Familiarity with these disorders and of their pathophysiologic mechanisms is important to avoid unnecessary diagnostic delays.