In and around the pineal gland: a neuroimaging review.

Lesions arising in or around the pineal gland comprise a heterogeneous group of pathologies ranging from benign non-neoplastic cysts to highly malignant neoplasms. Pineal cysts are frequently encountered as an incidental finding in daily radiology practice but there is no universal agreement on the criteria for, frequency of, and duration of follow-up imaging. Solid pineal neoplasms pose a diagnostic challenge owing to considerable overlap in their imaging characteristics, although a combination of radiological appearances, clinical findings, and tumour markers allows for narrowing of the differential diagnosis. In this review, we describe the radiological anatomy of the pineal region, clinical symptoms, imaging appearances, and differential diagnosis of lesions arising in this area, and highlight the clinical management of these conditions.

Normative dimensions and symmetry of the lacrimal drainage system on dacryocystography: statistical analysis of morphometric characteristics.

BACKGROUND: Asymmetric lacrimal flow occurs in females more than males. We hypothesised that the normal lacrimal drainage system (LDS) may show subtle left-right asymmetry in morphometry when imaged on dacryocystography (DCG). MATERIALS AND METHODS: We retrospectively reviewed 60 normal bilateral LDSs.Images were analysed for 7 parameters: (1) combined length of either the superior or inferior canaliculus plus common canaliculus, (2) angle of insertion of common canaliculus into lacrimal sac (LS), (3, 4) length and width of the LS, (5) length of the naso lacrimal duct (NLD), and (6, 7) width of proximal and distal NLD. We tested the effect of independent variables (age, gender, and side) on each dependent variable (length, width, or angle) using regression analysis. We used a Studentt-test for independent samples to statistically compare bilateral LDSs. RESULTS: Patient median age was 62 years, and male:female ratio was 27:73. Mean dimensions and angles for all LDSs were: (1) 14.5 mm, (2) 57°,(3) 11.6 mm, (4) 2.1 mm, (5) 20.7 mm, (6) 1.4 mm, and (7) 1.8 mm. No independent variable affected variation in length, width, or angle. No significant difference emerged between dimensions of right and left LDSs in both sexes. CONCLUSIONS: A degree of affective lateralisation in the brain is known to result in lacrimal flow asymmetry after mood manipulation. We show that this is not reflected in LDS anatomy. Moreover, our detailed morphometric data can aid in therapeutic planning of LDS luminal procedures, especially when DCG images of one LDS are used as a road map for contralateral interventions.

Gold nanoparticles: a revival in precious metal administration to patients.

Gold has been used as a therapeutic agent to treat a wide variety of rheumatic diseases including psoriatic arthritis, juvenile arthritis, and discoid lupus erythematosus. Although the use of gold has been largely superseded by newer drugs, gold nanoparticles are being used effectively in laboratory based clinical diagnostic methods while concurrently showing great promise in vivo either as a diagnostic imaging agent or a therapeutic agent. For these reasons, gold nanoparticles are therefore well placed to enter mainstream clinical practice in the near future. Hence, the present review summarizes the chemistry, pharmacokinetics, biodistribution, metabolism, and toxicity of bulk gold in humans based on decades of clinical observation and experiments in which gold was used to treat patients with rheumatoid arthritis. The beneficial attributes of gold nanoparticles, such as their ease of synthesis, functionalization, and shape control are also highlighted demonstrating why gold nanoparticles are an attractive target for further development and optimization. The importance of controlling the size and shape of gold nanoparticles to minimize any potential toxic side effects is also discussed.

Experimental radiosurgery simulations using a theoretical model of cerebral arteriovenous malformations.

BACKGROUND AND PURPOSE: A novel biomathematical arteriovenous malformation (AVM) model based on electric network analysis was used to investigate theoretically the potential role of intranidal hemodynamic perturbations in elevating the risk of rupture after simulated brain AVM radiosurgery. METHODS: The effects of radiation on 28 interconnected plexiform and fistulous AVM nidus vessels were simulated by predefined random or stepwise occlusion. Electric circuit analysis revealed the changes in intranidal flow, pressure, and risk of rupture at intervals of 3 months during a 3-year latency period after simulated partial/complete irradiation of the nidus using doses <25 and >/=25 Gy. An expression for risk of rupture was derived on the basis of the functional distribution of the critical radii of component vessels. The theoretical effects of radiation were also tested on AVM nidus vessels with progressively increasing elastic modulus (E:) and wall thickness during the latency period, simulating their eventual fibrosis. RESULTS: In an AVM with E=5. 0x10(4) dyne/cm(2), 4 (14.3%) of a total 28 sets of AVM radiosurgery simulations revealed theoretical nidus rupture (risk of rupture >/=100%). Three of these were associated with partial nidus coverage and 1 with complete treatment. All ruptures occurred after random occlusion of nidus vessels in AVMs receiving low-dose radiosurgery. Intranidal hemodynamic perturbations were observed in all cases of AVM rupture; the occlusion of a fistulous component resulted in intranidal rerouting of flow and escalation of the intravascular pressure in adjacent plexiform components. Risk of rupture was found to correlate with nidus vessel wall strength: a low E: of 1.9x10(4) dyne/cm(2) resulted in a 92.8% incidence of AVM rupture, whereas a higher E: of 7.0x10(4) dyne/cm(2) resulted in only a 3.6% incidence of AVM rupture. A dramatic reduction in rupture incidence was observed when increasing fibrosis of the nidus was modeled during the latency period. CONCLUSIONS: It was found that the theoretical occurrence of AVM hemorrhage after radiosurgery was low, particularly when radiation-induced fibrosis of nidus vessels was considered. When rupture does occur, it would appear from a theoretical standpoint that the occlusion of intranidal fistulas or larger-caliber plexiform vessels could be a significant culprit in the generation of critical intranidal hemodynamic surges resulting in nidus rupture. The described AVM model should serve as a useful research tool for further theoretical investigations of cerebral AVM radiosurgery and its hemodynamic sequelae.

Experimental models of bifurcation and terminal aneurysms: construction techniques in swine.

We report our preliminary experience in the surgical construction of five experimental bifurcation and terminal aneurysm models in swine. We used unilateral neck vessels to construct models in which the relative directions and sizes of the parent and daughter arteries could be varied by surgery, resulting in aneurysms with high morphologic similarity to human intracranial lesions. Steps in the construction of each model are detailed.

Acute subdural hemorrhage complicating embolization of a cerebral arteriovenous malformation.

We present a case of a young adult in whom acute subdural hemorrhage developed immediately after embolization of a cerebral arteriovenous malformation with glue. Inadvertent venous outlet obstruction with glue was implicated in the production of the hemorrhage. Possible mechanisms of spread of blood to the subdural space are discussed. Awareness of the possibility of iatrogenic subdural hemorrhage is necessary before undertaking embolization procedures.

Endovascular treatment of arteriovenous malformations with selective intranidal occlusion by detachable platinum electrodes: technical feasibility in a swine model.

The technical feasibility of selective intranidal endovascular occlusion of experimental arteriovenous malformations with detachable superfine platinum electrodes was assessed in a swine model. The delivery and release of electrodes were performed within normal carotid retia mirabilia, the faster-flowing nidus (bilateral retia) of a carotid-jugular fistula-type model of an arteriovenous malformation, and a small-caliber H-type direct arteriovenous fistula. Controllable atraumatic placement of the electrodes was possible deep within each rete and in the middle of the fistula. The devices were soft and flexible, allowing them to conform to the tight turns and branches of rete vessels. Marked diminution of flow was achieved by release of multiple devices within each rete. Migration of the electrode occurred when detached within the larger-caliber arteriovenous fistula. The main advantages of this technique appear to be the controlled delivery and assured release of an occlusive radiopaque embolic agent within the nidus.

Endovascular treatment of multiple aneurysms involving the posterior intracranial circulation.

The results of surgery on multiple intracranial aneurysms tha involve the vertebrobasilar circulation are poor, and associated patient mortality remains high. We describe the endovascular treatment of four patients with mutiple aneurysms that involved the posterior intracrancial circulation. Satisfactory occlusion of all aneurysms was achieved by using electrolytically detachable coils, and all patients had a good clinical recovery. Our early experience suggests that endovascular coil occlusion may be a particularly suitable method for treating this high-risk condition.

Predictors of aneurysmal occlusion in the period immediately after endovascular treatment with detachable coils: a multivariate analysis.

BACKGROUND AND PURPOSE: Complete intracranial aneurysmal occlusion by endovascular techniques is required for successful treatment and is presumably influenced by several parameters. The purpose of this study was to investigate whether operator experience and angiographic characteristics of intracranial aneurysms correspond to the degree of endovascular occlusion in the period immediately after treatment with Guglielmi detachable coils (GDCs). METHODS: Pre- and posttreatment angiograms of 72 patients undergoing GDC treatment were reviewed retrospectively. The following angiographic characteristics of the aneurysms were evaluated: largest diameter of the sac, volume, neck size, shape, type, cerebrovascular site, surroundings, and likely direction of aneurysmal inflow as judged by a score developed by measuring aneurysm/parent artery angulation. The chronological sequence in which the aneurysms were treated was used as a measure of operator experience. A chi2-test was used to identify parameters that correlated with outcomes of total (100%) or partial (<100%) occlusion. A multivariate analysis was used to determine the factors most predictive of aneurysmal occlusion at therapy. RESULTS: Parameters that correlated with the unsatisfactory result of partial occlusion were large aneurysmal diameter, volume, and neck size, more direct inflow (ie, increasingly obtuse aneurysm/parent artery angulation), and early chronological presentation in the series. The three factors most predictive of partial occlusion were large aneurysmal diameter, more direct inflow, and early chronological order of treatment. CONCLUSION: Several morphologic features of aneurysms were identified to help predict the immediate outcome of occlusion with GDCs. This study underscores the existence of a steep learning curve associated with GDC use in treating aneurysms and the importance of operator experience in achieving optimal therapeutic results.

Laboratory evaluation of a microangioscope for potential percutaneous cerebrovascular applications.

A laboratory-based study of the physical and performance characteristics of a new 0.25-mm-thin microangioscope was performed. The microangioscope tested was compatible with currently available microcatheters, but its tip was considerably stiff and of limited radiopacity. Poor image quality and difficult image interpretation were further drawbacks. Intensive efforts are directed at addressing current limitations and testing further innovations that could pave the way for future performance in neurovascular endoscopy.

Can induction of systemic hypotension help prevent nidus rupture complicating arteriovenous malformation embolization?: analysis of underlying mechanism achieved using a theoretical model.

BACKGROUND AND PURPOSE: Nidus rupture is a serious complication of intracranial arteriovenous malformation (AVM) embolotherapy, but its pathogenetic mechanisms are not well described. An AVM model based on electrical network analysis was used to investigate theoretically the potential role of hemodynamic perturbations for elevating the risk of nidus vessel rupture (Rrupt) after simulated AVM embolotherapy, and to assess the potential benefit of systemic hypotension for preventing rupture. METHODS: Five separate hypothetical mechanisms for nidus hemorrhage were studied: 1) intranidal rerouting of blood pressure; 2) extranidal rerouting of blood pressure; 3) occlusion of draining veins with glue; 4) delayed thrombosis of draining veins; and 5) excessively high injection pressures proximal to the nidus. Simulated occlusion of vessels or elevated injection pressures were implemented into the AVM model, and electrical circuit analysis revealed the consequent changes in intranidal flow, pressure, and Rrupt for the nidus vessels. An expression for Rrupt was derived based on the functional distribution of the critical radii of component vessels. If AVM rupture was observed (Rrupt > or = 100%) at systemic normotension (mean pressure [P] = 74 mm Hg), the theoretical embolization was repeated under systemic hypotension (minor P = 70 mm Hg, moderate P = 50 mm Hg, or profound P = 25 mm Hg) to assess the potential benefit of this maneuver in reducing hemorrhage rates. RESULTS: All five pathogenetic mechanisms under investigation were able to produce rupture of AVMs during or after embolotherapy. These different mechanisms had in common the capability of generating surges in intranidal hemodynamic parameters resulting in nidus vessel rupture. The theoretical induction of systemic hypotension during and after treatment was shown to be of significant benefit in attenuating these surges and reducing Rrupt to safer levels below 100%. CONCLUSION: The induction of systemic hypotension during and after AVM embolization would appear theoretically to be of potential use in preventing iatrogenic nidus hemorrhage. The described AVM model should serve as a useful research tool for further theoretical investigations of AVM embolotherapy and its hemodynamic sequelae.

Histopathologic characteristics of a chronic arteriovenous malformation in a swine model: preliminary study.

BACKGROUND AND PURPOSE: The experimental induction of histologic transformations in microvessels of similar caliber to those of nidus vessels of cerebral arteriovenous malformations (AVMs) has not been attempted previously. Our goal was to examine preliminarily the histopathologic characteristics of nidus vessels and the angiographic features of a chronic AVM model in swine. METHODS: AVM models were fashioned from bilateral carotid retia mirabilia of seven swine after the surgical formation of large unilateral carotid-jugular fistulas. One AVM model was made for immediate use, whereas in the other six, follow-up angiography was obtained at varying intervals (2 to 180 days) after model creation. Light and electron microscopy, immunohistochemistry (using monoclonal antibodies against smooth muscle actin and PC10 against proliferating cell nuclear antigen), and histometry were performed on the nidus vessels of three swine: one acutely created, one 2 months old, and one 6 months old. RESULTS: Vascular dilatation and tortuosity of the main arterial feeder and draining vein were evident angiographically as early as 4 days after AVM creation, and were maximal in the 6-month-old model. Compared with the acutely created nidus vessels, those in the two chronic models revealed disrupted and attenuated elastica and intimal hyperplasia that was focal ("cushions") or generalized, leading to luminal occlusion. Variable numbers of cells in the tunica media of chronic nidus vessels contained smooth muscle actin. PC10/proliferating cell nuclear antigen immunoreactivity was observed in the endothelium and subendothelial layers. Histometry showed increases in intimal hyperplasia and medial thickness in the chronic vessels. CONCLUSION: Nidus vessels in this chronic swine AVM model exhibited striking histologic changes similar to those seen in cerebral AVMs. The induced vessel growth seen angiographically and histologically in components of the chronic AVMs was consistent with the presence of persistently raised intravascular hemodynamic loads. This preliminary feasibility study suggests that the realistic histologic characteristics of this chronic AVM model are an attractive feature, and if confirmed in future, more comprehensive, studies would be of benefit in accurate histopathologic interpretation of the effects of superimposed experimental embolotherapy or radiosurgery. This model may provide a useful experimental tool to study the dynamic cellular and tissue events that dictate the development and natural history of AVMs.

Aneurysms related to cerebral arteriovenous malformations: superselective angiographic assessment in 58 patients.

PURPOSE: To report the comprehensive superselective angiographic characteristics of aneurysms associated with cerebral arteriovenous malformations. METHOD: One hundred consecutive patients referred for cerebral arteriovenous malformation embolization underwent preembolization superselective angiography. Superselective angiograms were obtained after microcatheterization of arteriovenous malformation pedicles, and assessed for number and location of aneurysms related to the malformation. A chi 2 test was conducted to correlate these parameters with the onset of intracranial hemorrhage. RESULTS: Aneurysms were demonstrated in 58 of 100 patients. Single aneurysms were found in 24 patients and multiple aneurysms in 34. Presence and number of aneurysms were found to correlate significantly with a clinical presentation of hemorrhage. CONCLUSION: Superselective angiography was found to be of paramount importance in elucidating the precise and detailed angioarchitecture of brain arteriovenous malformations.

Combined stent implantation and endosaccular coil placement for treatment of experimental wide-necked aneurysms: a feasibility study in swine.

PURPOSE: To assess the feasibility of combining stent implantation in the parent artery with endosaccular coil placement for the treatment of experimentally created wide-necked aneurysms. METHODS: Wide-necked aneurysms were surgically created on the common carotid artery in 12 swine. A metal stent was endovascularly implanted across each aneurysm neck and its effect documented anigiographically. If the aneurysm remained patent, a microcatheter was introduced into the aneurysm through the stent mesh. Electrically detachable coils were delivered into the aneurysm sac to produce thrombosis. RESULTS: After stent implantation, one carotid artery thrombosed and two aneurysms spontaneously occluded. In the other 9 cases, coils were deposited through the stent to occlude the aneurysm. Complete aneurysm packing was possible in all 9 cases. The presence of the stent allowed placement of small coils near the aneurysm neck, thus contributing to the safe occlusion of small remnants in the final stages of aneurysm packing. CONCLUSION: The combination of stent implantation and coil placement is feasible in the treatment of experimental wide-necked saccular aneurysms. The stent maintains patency of the parent artery while allowing aneurysm occlusion by endosaccular coil placement through the stent's mesh. Occlusion of small aneurysm remnants is possible with no fear of coil hernation or migration into the parent artery. Long-term studies will be necessary before application to treatment of selected intracranial aneurysms.

Epilepsy associated with cerebral arteriovenous malformations: a multivariate analysis of angioarchitectural characteristics.

PURPOSE: To identify the morphological vascular characteristics of cerebral arteriovenous malformations (AVMs) that predict a clinical presentation of epilepsy. METHOD: Fifteen angioarchitectural characteristics of brain AVMs were selected for assessment in 100 consecutive patients referred to our institution for endovascular treatment. In this population, 47% of the AVMs were diagnosed as a consequence of epilepsy. The angioarchitectural characteristics and population demographics were statistically analyzed by means of multivariate analysis. RESULTS: The following six parameters were found to be the most predictive of epilepsy: cortical location of the AVM, feeding by the middle cerebral artery, cortical location of the feeder, absence of aneurysms, presence of varix/varices in the venous drainage, and association of varix and absence of intranidal aneurysms. Three factors were not among the most predictive factors of epilepsy but were significantly associated with the onset of seizures: AVM feeding by the external carotid artery, a temporal cortical location, and a parietal cortical location. CONCLUSION: Detailed analysis of the angioarchitecture of intracranial AVMs has helped us identify features that strongly correlate with epilepsy. This may aid in future understanding of the physiopathologic mechanisms in epilepsy associated with AVMs, and in identifying goals of treatment for epileptogenic AVMs.

Collagen microbeads: experimental evaluation of an embolic agent in the rete mirabile of the swine.

PURPOSE: To evaluate the histologic and angiographic effects of collagen microbeads as an embolic agent in the swine rete mirabile. METHODS: Human collagen particles (380 +/- 100 microns) of spheroidal shape and smooth surface were used to embolize the rete mirabile in five swine. Control angiograms and pathologic examinations were obtained immediately and sequentially from 3 to 35 days after embolization. RESULTS: The collagen particles were easy to inject through microcatheters. Embolization was always angiographically complete and persistent for at least 5 weeks. Histologic studies showed occlusion of 25% to 50% of the rete vessels. After 3 and 5 weeks' follow-up, transmural and adventitial chronic inflammation was present. Inflammatory infiltrates included lymphohistiocytic cells and scattered eosinophils. The foreign-body giant-cell reaction was pronounced. No evidence of angionecrosis or focal hemorrhage was shown. CONCLUSIONS: Collagen microbeads are a promising experimental embolic agent, with potential future applications in humans.

An experimental arteriovenous malformation model in swine: anatomic basis and construction technique.

We assessed the feasibility of creating an experimental arteriovenous malformation model in swine by diverting and increasing blood flow through bilateral retia mirabilia. This was achieved by surgical formation of a large right-sided carotid-jugular fistula, in combination with endovascular occlusion of several neck arteries ipsilateral to the fistula. Using this technique, 11 of 13 swine demonstrated an acute-phase angiographic simulation of an arteriovenous malformation. There was rapid circulatory diversion from the left ascending pharyngeal artery ("feeder"), across both retia ("nidus"), and fast retrograde flow into the right ascending pharyngeal and common carotid arteries ("draining vein") toward the fistula. The relevant vascular anatomy of the swine head and neck is outlined, and steps in the construction of this arteriovenous malformation model are detailed.

Endovascular treatment of fusiform aneurysms with stents and coils: technical feasibility in a swine model.

PURPOSE: To assess the biomechanical feasibility of treating experimental fusiform aneurysms endovascularly with a combination of stents and coils. METHODS: An experimental model was surgically constructed in the necks of nine swine to simulate intracranial fusiform aneurysms possessing important "perforators" or side branches. Balloon-expandable metal stents were positioned across the aneurysms in eight swine. In five of these, additional treatment was intraaneurysmal placement of detachable microcoils. Attempts were made to deposit these coils strategically away from the origin of the side branch. RESULTS: Stent placement was successful in seven swine but failed in one swine because of stent-aneurysm size mismatch. Two swine treated with only stents showed no significant alterations in blood filling of the aneurysm or side branch. Satisfactory coil placement (outside the stent, within the aneurysm sac, and away from the orifice of the side branch) was achieved in four of the five swine treated with stents and coils. Careful fluoroscopic monitoring and controlled coil delivery were necessary to avoid covering the sidebranch origin. These aneurysms could not be packed densely after detachment of the first coil because of the resultant radiographic overlap of multiple coil loops on the stent and its lumen in all projections. In one swine there was inadvertent untoward reentry of the coil tip into the expanded stent lumen during its delivery. CONCLUSION: Endovascular treatment of experimental fusiforms aneurysms using stents and coils is technically feasible. The stent maintains patency of the parent artery while allowing strategic coil placement in the aneurysm sac away from the origin of side branches. This technique may prove useful in the future treatment of intracranial fusiform aneurysms. However, potential sources of technical difficulties have been identified, and further longterm studies using an appropriate intracranial stent will be necessary before human application.

Arteriovenous malformation animal model for radiosurgery: the rete mirabile.

PURPOSE: To study the effects of single-dose radiation on the porcine rete mirabile, a tangle of microvessels that mimics human arteriovenous malformations of the brain. METHODS: Eight retia mirabilia received a single dose of radiation under stereotactic location with digital angiography and CT. The following doses were applied: 20, 30, 40, 50, 60, 70, 80, and 90 Gy. The animals were followed up for a period of 7 months. Findings at neurologic examination, serial angiography, and histopathologic examination were analyzed. RESULTS: Progressive occlusion as observed by angiography corresponded to the histopathologic finding of intimal hyperplasia; that is, marked thickening of the vessel wall, progressing to occlusion of the vascular lumen, and associated thrombosis. A direct dose response was noted for these changes. Neurologic findings were related to the dose distribution and to histologic findings in structures adjacent to the rete mirabile. CONCLUSION: The rete mirabile is an excellent model by which to study the radiologic and histologic effects of single-dose radiation to the microvasculature of the central nervous system.

Laboratory simulations and training in endovascular embolotherapy with a swine arteriovenous malformation model.

We assessed the suitability of a swine experimental arteriovenous malformation model for laboratory simulations and training in endovascular embolotherapy. Embolizations with liquid glue or particles were performed in 10 animals. The parameters of injection (microcatheter position, concentration and volume of embolic agent, injection rate) were deliberately varied to simulate results that may be observed in clinical practice. A range of successful and less desirable therapeutic outcomes or complications was simulated. In one model, intravascular mean blood pressure in the "terminal feeder" rose after "nidus" embolization, consistent with observations in feeders of cerebral arteriovenous malformations. Experience in the technical aspects of embolotherapy was gained by repeated performances using this model. Simplicity of creation, clear angiographic visibility of feeders, a nidus and a draining vein, and hemodynamic similarities with cerebral arteriovenous malformations make this an attractive in vivo experimental model for learning the principles of embolotherapy, testing new embolic agents, and training/gaining experience in embolization techniques.