Dual-beam Fourier domain optical Doppler tomography of zebrafish.

We have developed a dual-beam Fourier domain optical Doppler tomography (FD-ODT) system to image zebrafish (Danio rerio) larvae. Two beams incident on the zebrafish with a fixed angular separation allow absolute blood flow velocity measurement to be made regardless of vessel orientation in a sagittal plane along which the heart and most of the major vasculature lie. Two spectrometers simultaneously acquire spectra from two interferometers with a typical (maximum) line rate of 18 (28) kHz. The system was calibrated using diluted milk and microspheres and a 0.5-mm thick flow cell. The average deviation from the set velocity from 1.4 to 34.6 mm/s was 4.1%. Three-dimensional structural raster videos were acquired of an entire fish, and through the head, heart, and upper tail of the fish. Coarse features that were resolved include the telencephalon, retina, both heart chambers (atrium and ventricle), branchial arches, and notochord. Other fine structures within these organs were also resolved. Zebrafish are an important tool for high-throughput screening of new pharmacological agents. The ability to generate high-resolution three-dimensional structural videos and accurately measure absolute flow rates in major vessels with FD-ODT provides researchers with additional metrics by which the efficacy of new drugs can be assessed.

Three dimensional tracking for volumetric spectral-domain optical coherence tomography.

We present a three-dimensional (3D) tracker for a clinical ophthalmic spectral domain optical coherence tomography (SD-OCT) system that combines depth-tracking with lateral tracking, providing a stabilized reference frame for 3D data recording and post acquisition analysis. The depth-tracking system is implemented through a real-time dynamic feedback mechanism to compensate for motion artifact in the axial direction. Active monitoring of the retina and adapting the reference arm of the interferometer allowed the whole thickness of the retina to be stabilized to within +/-100 mum. We achieve a relatively constant SNR from image to image by stabilizing the image of the retina with respect to the depth dependent sensitivity of SD-OCT. The depth tracking range of our system is 5.2 mm in air and the depth is adjusted every frame.nhancement in the stability of the images with the depth-tracking algorithm is demonstrated on a healthy volunteer.

Hybrid retinal imager using line-scanning laser ophthalmoscopy and spectral domain optical coherence tomography.

We demonstrate for the first time the integration of two technologies, Spectral Domain Optical Coherence Tomography (SDOCT) and Line-Scanning Laser Ophthalmoscopy (LSLO) into a single compact instrument that shares the same imaging optics and line scan camera for both OCT and LSLO imaging. Co-registered high contrast wide-field en face retinal LSLO and SDOCT images are obtained non-mydriatically with less than 600 microwatts of broadband illumination at 15 frames/sec. The LSLO/SDOCT hybrid instrument could have important applications in clinical ophthalmic diagnostics and emergency medicine.

Noninvasive ventilation during gastrostomy tube placement in patients with severe duchenne muscular dystrophy: case reports and review of the literature.

Individuals with Duchenne muscular dystrophy may benefit from gastrostomy tube feeding due to progressive dysphagia and malnutrition. However, due to their severely impaired pulmonary function, these individuals are at risk of severe complications when they are sedated or undergo anesthesia for the procedure. We previously described a technique of noninvasive positive pressure ventilation to provide respiratory support during gastrostomy tube placement in such patients, but this technique had risks and limitations. In this case report, we examine two alternative techniques we used to provide respiratory support successfully to patients with severe muscular dystrophy and malnutrition who underwent percutaneous endoscopic gastrostomy tube placement. We then review the literature and discuss the potential benefits, risks, and limitations of the above techniques and of other options for gastrostomy placement in people with severe muscular dystrophy.

Cerebral intraarterial fibrinolysis at the crossroads: is a phase III trial advisable at this time?

PURPOSE: To describe the rationale for fibrinolysis, review the state of the art in cerebral fibrinolysis, and discuss whether it is time for phase III studies of cerebral intraarterial fibrinolysis. METHODS: Critical review of the literature with statistical reevaluation of significant clinical data. RESULTS: There are abundant phase III data supporting the use of thrombolysis in the cardiovascular system. However, there are no published phase III trials of intraarterial fibrinolysis in stroke. All reports of cerebral intraarterial fibrinolysis are case series. The studies are typically small with variable treatment protocols and designs that are susceptible to bias. The only analysis comparing cerebral intraarterial fibrinolysis with conventional therapy is based on nonconcurrent controls. CONCLUSIONS: Stroke is common and costly. Acute stroke intervention with fibrinolytic drugs is theoretically justified. Studies done to date have significant, inferential limitations. The data suggest an association between thrombolysis, recanalization, and prognosis. However, imprecision and inadequate control of systematic error preclude conclusions regarding clinical outcomes. Randomized, controlled trials are needed to establish the clinical value of cerebral local intraarterial fibrinolysis. However, cerebral local intraarterial fibrinolysis availability, the cerebral local intraarterial arterial fibrinolysis learning curve, anticipated technological advances, unresolved procedural controversies, and ethical and fiscal considerations make a large phase III trial impractical and ill-advised at the present time. Additional basic research is needed to set the stage for a successful clinical trial.

Initial in vivo results of a hybrid retinal photocoagulation system.

We describe initial in vivo experimental results of a new hybrid digital and analog design for retinal tracking and laser beam control. An overview of the design is given. The results show in vivo tracking rates which exceed the equivalent of 38 degrees/s in the eye. A robotically assisted lesion pattern is created for laser surgery to treat conditions such as diabetic retinopathy and retinal breaks.

Three-dimensional reconstruction of arteriovenous malformations from multiple stereotactic angiograms.

Stereotactic angiography is the preferred imaging modality in the radiosurgical treatment of arteriovenous malformations (AVM). A major limitation of this technique is the inability to determine the three-dimensional shape and the volume of the AVM. We developed a technique for reconstructing the AVM from multiple stereotactic angiograms. The fiducial marks and the identified target area are digitized for each view. The 2-D target area is then stereotactically backprojected into a 3-D volume. The spatial boundary of the target volume is defined by superimposing the backprojections from each of the views. In feasibility studies with a phantom, this technique accurately reconstructed complex 3-D structures, depicting fine details as small as 1 mm. Clinical studies in two patients indicated that this novel technique is very useful for the 3-D reconstruction of AVM for radiosurgical treatment. The number of views required depends on the complexity of the object. In general, six to eight views appear adequate. The accuracy of the reconstruction can be compromised if the view angles are limited as with the current radiographic frame. A new frame design with practically unlimited view angles is proposed to avoid this potential limitation. However, structures that are always obscured (such as concavity) could not be accurately reconstructed, leading to overestimates of the object size. This "limitation" has a positive side, in that the technique will not underestimate the actual target volume. The ability to delineate both the shape and volume of the lesion should facilitate optimal target coverage while sparing a significant amount of normal tissue.

Preoperative superselective arteriolar embolization: a new approach to enhance resectability of spinal tumors.

The extent of surgical resection of spinal tumors is frequently limited by blood loss and technical difficulty associated with the vascularity of the tumors. We report here the use of superselective percutaneous arterial embolization to reduce the rate of blood loss at the time of surgical resection and enhance resectability. The types of tumors treated were metastatic renal carcinoma, metastatic thyroid carcinoma, metastatic melanoma, and giant cell tumor of the sacrum. Two of the patients required repeated embolization and surgery for recurrent symptoms. The estimated blood loss in seven of nine procedures performed on the six patients ranged from 300 to 800 ml, after which no transfusion was required. In two procedures, extensive resection of very large tumors resulted in larger losses of blood, and postoperative transfusion was necessary. No significant complications of embolization or surgery occurred. A key factor in our embolization technique is the use of microfibrillar collagen, which allows occlusion of tumor vessels as small as 20 microns and may prevent reconstitution of the embolized vessels by collateral flow. We conclude that preoperative arterial embolization enhances the resectability of a variety of spinal tumors by reducing intraoperative blood loss. This may provide an additional benefit by reducing the risk related to postoperative transfusion. By permitting a more aggressive surgical approach, the use of preoperative embolization also has the potential to improve outcome in patients with spinal tumors.

Medical management in the endovascular treatment of carotid-cavernous aneurysms.

Carotid-cavernous aneurysms account for between 1.9% and 9.0% of intracranial aneurysms. Entirely intercavernous aneurysms are believed to have a relatively benign course, with cranial nerve findings or headache being the usual initial symptomatology; however, subarachnoid hemorrhage or carotid-cavernous fistula formation can result from rupture. Over the past 15 years endovascular parent artery occlusion has essentially replaced surgical carotid occlusion as the treatment of choice. The authors describe a series of 39 consecutive patients at the University of Virginia Health Sciences Center who underwent endovascular treatment of a carotid-cavernous aneurysm. Aggressive invasive hemodynamic monitoring and maintenance of a state of normo- to mild hypervolemia in the asymptomatic patient was used throughout the periprocedural period. Rapid institution of hypervolemic-hypertensive therapy can reverse early neurological deficits related to hypoperfusion in these patients. Only one individual managed with this protocol developed neurological deficits not reversible with hypertensive-hypervolemic therapy. Heparin therapy was administered for 48 hours after occlusion, with patients receiving subsequent aspirin therapy for 6 months to combat distal embolism secondary to thrombosis. Long-term complications were not seen in patients receiving aneurysm trapping; however, two individuals with proximal carotid occlusion developed late optic neuropathy and one had recurrent transient ischemic attacks that ceased with supraclinoidal carotid clipping.

Pulsatile tinnitus cured by angioplasty and stenting of petrous carotid artery stenosis.

Pulsatile tinnitus may result from turbulent flow within the ipsilateral internal carotid artery. Surgical endarterectomy and carotid artery ligation have been used to treat atherosclerotic stenosis with or without associated pulsatile tinnitus. To our knowledge, this is the first reported case of pulsatile tinnitus, attributable to internal carotid artery stenosis, successfully treated by angioplasty and stenting.

Endovascular revascularization therapy in cerebral athero-occlusive disease. Angioplasty and stents, systemic and local thrombolysis.

Most strokes result from thrombosis or embolism. Many of these are amenable to endovascular therapies, which based on experience to date, appear to prevent the occurrence or mitigate the effects of these events. The ultimate role, however, of CPTA, CLIF, and intravascular stenting remains to be defined and validated through comparative studies with established alternative surgical and medical therapies.

[Reflection measurement during retinal laser coagulation in patients. Development of an automatically controlled dosimeter]. / Reflexionsmessung während Netzhautlaserkoagulationen bei Patienten. Entwicklung einer automatisch gesteuerten Dosiseinrichtung.

PURPOSE: Retinal laser coagulation has limited reproducibility, because every laser exposition is unpredictably affected by pigmentation and media opacities. This can lead to complications. A feedback-controlled dosimeter would make retinal laser treatment a safer, more reproducible and faster procedure. METHOD: A reflectometer was developed that allows monitoring of the reflection of laser light during standard photocoagulation. Hundreds of coagulations in rabbit eyes and about 12,000 coagulations in patients undergoing routine laser treatment were recorded. RESULTS: The results of the first reflectance measurements in humans are presented along with extensive animal studies. A typical reflectance history was found for different lesion intensities. The degree of retinal whitening correlates with reflectance characteristics. These characteristics allow an early prediction of lesion intensity. Motion during laser exposure affects each coagulation in a fashion similar to spot size and exposure time. CONCLUSION: Reflectometry is the currently most effective means of monitoring lesion development. An automatic dosimeter for retinal photocoagulation seems feasible.

Mammary tumor growth and pulmonary metastasis are enhanced in a hyperlipidemic mouse model.

Dyslipidemia has been associated with an increased risk for developing cancer. However, the implicated mechanisms are largely unknown. To explore the role of dyslipidemia in breast cancer growth and metastasis, we used the apolipoprotein E (ApoE) knockout mice (ApoE(-/-)), which exhibit marked dyslipidemia, with elevated circulating cholesterol and triglyceride levels in the setting of normal glucose homeostasis and insulin sensitivity. Non-metastatic Met-1 and metastatic Mvt-1 mammary cancer cells derived from MMTV-PyVmT/FVB-N transgenic mice and c-Myc/vegf tumor explants respectively, were injected into the mammary fat pad of ApoE(-/-) and wild-type (WT) females consuming a high-fat/high-cholesterol diet and tumor growth was evaluated. ApoE(-/-) mice exhibited increased tumor growth and displayed a greater number of spontaneous metastases to the lungs. Furthermore, intravenous injection of Mvt-1 cells resulted in a greater number of pulmonary metastases in the lungs of ApoE(-/-) mice compared with WT controls. To unravel the molecular mechanism involved in enhanced tumor growth in ApoE(-/-) mice, we studied the response of Mvt-1 cells to cholesterol in vitro. We found that cholesterol increased Akt(S473) phosphorylation in Mvt-1 cells as well as cellular proliferation, whereas cholesterol depletion in the cell membrane abrogated Akt(S473) phosphorylation induced by exogenously added cholesterol. Furthermore, in vivo administration of BKM120, a small-molecule inhibitor of phosphatidylinositol 3-kinase (PI3K), alleviated dyslipidemia-induced tumor growth and metastasis in Mvt-1 model with a concomitant decrease in PI3K/Akt signaling. Collectively, we suggest that the hypercholesterolemic milieu in the ApoE(-/-) mice is a favorable setting for mammary tumor growth and metastasis.

Spectral-domain low coherence interferometry/optical coherence tomography system for fine needle breast biopsy guidance.

A novel technology and instrumentation for fine needle aspiration (FNA) breast biopsy guidance is presented. This technology is based on spectral-domain low coherence interferometry (SD-LCI). The method, apparatus, and preliminary in vitro/in vivo results proving the viability of the method and apparatus are presented in detail. An advanced tissue classification algorithm, preliminarily tested on breast tissue specimens and a mouse model of breast cancer is presented as well. Over 80% sensitivity and specificity in differentiating all tissue types and 93% accuracy in differentiating fatty tissue from fibrous or tumor tissue was obtained with this technology and apparatus. These results suggest that SD-LCI could help for more precise needle placement during the FNA biopsy and therefore could substantially reduce the number of the nondiagnostic aspirates and improve the sensitivity and specificity of the FNA procedures.

The role of ultrasound in the management of vein of Galen aneurysms in infancy.

Ultrasonography can be the key imaging modality for neonatal patients with vein of Galen aneurysms. Ultrasound can be used to diagnose the condition, monitor transtorcular embolization procedures, and follow-up these patients after embolization to assess the effectiveness of embolization and to check for complications.

Dynamic reflectometer for control of laser photocoagulation on the retina.

In retinal laser photocoagulation, constant exposure parameters do not result in identical lesions. This lack of reproducibility increases the rate of complications from over- or undertreatment and inhibits determination of the optimal treatment endpoints for different retinal disorders. To this end, a feedback-controlled photocoagulator could make retinal photocoagulation a safer, more reproducible, and faster procedure. A dynamic confocal reflectometer was integrated into a slit lamp laser delivery system. Real-time reflectance changes on the retinas of pigmented rabbits were obtained by monitoring the increasing back-scattered light of the coagulating beam during argon laser photocoagulation. Reproducible temporal reflectance patterns were measured that correlated with ophthalmoscopically assessed lesion intensity independent of the exposure parameters, the transparency of the optical media, and the focusing conditions. As a step toward the development of a feedback-controlled photocoagulator, the confocal reflectometer has been proven in animal trials closely resembling clinical practice.